biotechnology state of the industry report 2 • 0 • 0 • 6
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biotechnology state of the industry report 2 • 0 • 0 • 6
BIOWORLD ® BIOTECHNOLOGY STATE OF THE INDUSTRY R E P O R T 2 • 0 • 0 • 6 THE BIOWORLD® STATE OF THE INDUSTRY REPORT 2006 is published by Thomson BioWorld®, 3525 Piedmont Road, Building Six, Suite 400, Atlanta, GA 30305 USA. Opinions expressed are not necessarily those of this publication. Mention of products or services does not constitute endorsement. Thomson BioWorld® is a division of Thomson Healthcare. Copyright © 2006 Thomson BioWorld®. All Rights Reserved. No part of this publication may be reproduced without the written consent of Thomson BioWorld®. (GST Registration Number R128870672) Managing Editor: Brady Huggett. Senior Production Editor: Kay Torrance. Database Editor: Jim Shrine. Staff Writers: Karen Pihl-Carey, Jennifer Boggs. Science Editor: Anette Breindl. National Editor: Randall Osborne. Washington Editor: Aaron Lorenzo. Vice President/Group Publisher: Donald R. Johnston. Marketing Manager: Chris Walker. Account Representatives: Bob Sobel, Steve Roberts. Customer Service: (800) 688-2421 or (404) 262-5476. NO PART OF THIS PUBLICATION MAY BE REPRODUCED WITHOUT THE WRITTEN CONSENT OF THOMSON BIOWORLD®. To obtain photocopying rights or subscribe, please call (800) 688-2421. Table Of Contents I. Analysis Biotech Continues Growth In Quieter, Calmer Environment ................................................................................9 The Year In Review....................................................................................................................................................................1 1 The View From Wall Street ..................................................................................................................................................17 The View From Washington................................................................................................................................................22 The View From The Lab Bench..........................................................................................................................................25 II. Financial Data Discerning Market, Caution Drove Trends In Financing ......................................................................................33 Money Raised By Biotechnology Companies ............................................................................................................36 Initial Public Offerings ..........................................................................................................................................................37 Follow-On Offerings ............................................................................................................................................................42 After-Market Performance (Initial Public Offerings)................................................................................................49 After-Market Performance (Follow-On Offerings) ....................................................................................................50 Initial Public Offerings: 2002-2005 (Gross Proceeds By Month) ......................................................................53 Follow-On Offerings: 2002-2005 (Gross Proceeds By Month)............................................................................54 Gross Proceeds Of Biotech Public Stock Offerings: By Quarter 1995-2005..................................................55 Miscellaneous Financings Of Public Biotech Companies......................................................................................56 Venture Capital And Other Financings Of Private Biotechnology Firms ........................................................91 Milestones And Equity Investments From Corporate Partners ........................................................................121 Grants And Awards To Biotech Companies ..............................................................................................................134 III. Corporate Deals Major Playor Novartis Pays Big For Products, Platforms......................................................................................165 Biotechnology Mergers And Acquisitions..................................................................................................................169 Biotech-Big Pharma Collaborations: New Agreements ........................................................................................190 Biotech-Big Pharma Collaborations: Modified And Terminated Agreements ..........................................242 Manufacturing, Marketing And Distribution Agreements With Pharma Companies ............................250 Biotech-Biotech Deals: Collaborations, Agreements And Equity Participation ........................................260 Biotech-Biotech Collaborations: Modified And Terminated Agreements ..................................................300 Manufacturing, Marketing And Distribution Agreements Between Biotechnology Companies......302 Biotech Miscellaneous Collaborations........................................................................................................................309 Biotech-University/Nonprofit Institutions Collaborations ................................................................................312 Biotech-Agribusiness Collaborations..........................................................................................................................350 IV. Biotech Product Development Who’s To Blame For Fewer Approvals: FDA Or Biotech? ......................................................................................359 Biotechnology Products Approved By FDA In 2005 ............................................................................................363 Biotechnology Products On The Market ....................................................................................................................367 FDA Actions On Pending Applications In 2005 ......................................................................................................384 Licensing Applications Filed And Pending At FDA In 2005 ..............................................................................387 Products Not Recommended For Approval By FDA Advisory Panels In 2005 ..........................................393 Overseas Approvals And Actions In 2005................................................................................................................394 V. Report Card For Wall Street Methodology Used To Evaluate Underwriters’ Performance............................................................................405 Top 10 Underwriters: Full Credit To Lead Underwriters; Ranked By Gross Proceeds ............................406 Other Underwriters: Full Credit To Lead Underwriters; Ranked By Gross Proceeds..............................407 Top 10 Underwriters: Full Credit To All Underwriters; Ranked By Gross Proceeds ................................408 Other Underwriters: Full Credit To All Underwriters; Ranked By Gross Proceeds ..................................409 Top 9 Underwriters: IPOs (Full Credit To Lead Underwriters, Ranked By Gross Proceeds) ..................41 1 Other Underwriters: IPOs (Full Credit To Lead Underwriters, Ranked By Gross Proceeds ..................412 Top 10 Underwriters: IPOs (Full Credit To All Underwriters; Ranked By Gross Proceeds) ....................413 Other Underwriters: IPOs (Full Credit To All Underwriters; Ranked By Gross Proceeds)......................414 Top 9 Underwriters: IPO (Full Credit To Lead Underwriters; Ranked By After-Market Performance)......415 Other Underwriters: IPO (Full Credit To Lead Underwriters; Ranked By After-Market Performance)......416 Top 10 Underwriters: IPO (Full Credit To All Underwriters; Ranked By After-Market Performance) ......417 Other Underwriters: IPO (Full Credit To All Underwriters; Ranked By After-Market Performance)........418 VI. Stock Performance 2005 Stock Report: An Alphabetical Listing Of Public Biotech Companies................................................421 2005 British Stock Report ................................................................................................................................................427 2005 Canadian Stock Report ..........................................................................................................................................428 2005 Price Performance: Biotechnology Stocks Ranked By Percent Change For Year..........................429 Tracking The Overall Performance Of The 279 Stocks In BioWorld’s Universe ......................................433 BioWorld Stock Indicator Vs. Nasdaq Biotech Index ............................................................................................435 BIOWORLD ® A N A LY S I S Biotech Continues Growth In Quieter, Calmer Environment By Brady Huggett Managing Editor In many ways, 2005 looked a lot like 2004. Total money raised last year nearly equaled the year prior, when the industry raised $20.8 billion. There were 33 initial public offerings around the world in 2005, just slightly off from the 37 that completed in 2004. The markets were steady both years – BioWorld’s stock tracker showed the average biotech firm’s shares in 2005 lost just 2 percent, compared to the 2.5 percent gained in 2004. Those signs point to a leveling off for the sector, suggesting that gone are the days of an opening and then abruptly slamming IPO window, gone are collective plummeting and zooming of stock prices, based on a single firm’s news. Time and performance are wiping away both the skepticism and the foolish hype around biotech. The waters are calm. While that might not be as exciting as Nasdaq rocketing or wallowing, the schools of biotech firms moving beneath 2005’s smoother surface remained as interesting as ever. Biogen Idec Inc. was dealt a staggering blow in 2005, when its multiple sclerosis drug, Tysabri, was removed from the market due to links to progressive multifocal leukoencephalopathy. Once considered a potential blockbuster, the drug, when excised from Biogen Idec’s model, cost the company stock points, and it ended the year at $45.28, down 31.7 percent. Although in the first quarter of 2006 Tysabri seemed poised for a comeback, following an FDA panel’s positive recommendation in March to allow it back on the market, the deaths linked to the drug, coupled with 2004’s Vioxx turmoil, courtesy of Merck & Co. Inc., weighed on biotech investors early in 2005. BioWorld’s stock tracker hit its lowest point of the year in April, but 2005 progressed and stocks recovered, leaving April looking like nothing more serious than a market fluctuation – the industry has weathered those before. What bears mentioning about those 33 IPOs in 2005 – 16 in the U.S. – is the average take: $45.5 million. That’s about $10 million less than in 2004, and a long way from the 2000 average of $81 million. Far from supplying the exit some investors wanted, low IPO valuations helped drive a busy BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 9 2005 for mergers and acquisitions, highlighted by Novartis AG’s $5.1 billion bid for the shares it didn’t already own of Chiron Corp., and Amgen Inc.’s $2.2 billion offer for Abgenix Inc. Partnering was hot last year, too. Staring hard at their depleted pipelines, pharma firms were willing to buy less-mature products. Novartis again led the way, forming a Phase I deal with Anadys Pharmaceuticals Inc. worth up to $580 million including milestones, for Toll-like receptor drugs. Drug approvals, however, were down in 2005. The FDA approved 19 new drugs from biotech companies, four biotech-derived drugs from big pharma and 10 supplemental indications for already-approved drugs. Some suggest the agency is more cautious in the wake of Vioxx and Tysabri, but others blamed a fizzling of innovation in the labs of biotech firms. Either way, it didn't help matters when interim FDA head Lester Crawford in September suddenly stepped down, replaced by Andrew von Eschenbach. For all of biotech’s progress against disease, nature continues to provide new bugs to fight. In 2005, it was avian flu that had the world worrying. U.S. President George W. Bush asked for $7.1 billion to fight against a human pandemic, about half of which received clearance, and biotech firms are focused on developing vaccines. Regarding science, most notable last year was the disgracing of South Korean researcher Woo-Suk Hwang, unmasked as a fraud after an inquiry into his previously breathtaking work on human embryo cloning proved it was faked. As he fades into the wrong side of history, the scandal has legitimate researchers wondering if the bad taste he left behind will harm the future of stem cell research. The future of biotechnology? It seems secure. Nearly a third of all venture capital investment in 2005 went into the life sciences, and biotechnology appears to be taking its place as a member in good standing of the global economy. ■ 10 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 The Year In Review Public Scandals, But Big Money Put Up For Earlier-Stage Deals By Randall Osborne West Coast Editor Tysabri’s spectacular flameout, ongoing buzz about COX-2 inhibitors and a late-year scandal over faked stem-cell research failed to take the shine off a stellar 2005 in terms of money for biotechnology, which raised about $20 billion through financings and an estimated $14 billion more by way of partnering – a record number for the industry, if those numbers are added together. Biogen Idec Inc. and partner Elan Corp. plc pulled their much-celebrated Tysabri (natalizumab) off the market in the spring because of concerns over cases of progressive multifocal leukoencephalopathy just after an FDA panel voted to allow Merck & Co. Inc.’s painkiller Vioxx (rofecoxib) back on the shelf. Merck had yanked Vioxx voluntarily six months earlier because of cardiovascular side effects. A Texas jury in the summer had found Merck initially liable for $253 million, in the first of many lawsuits, and doubts lingered about COX-2 inhibitors as a class. Celebrex (celecoxib) and Bextra (valdecoxib), both from Pfizer Inc., were allowed to stay on the market, with “black box” warnings on their labels, similar to the one added to Vioxx. As 2006 began, Tysabri was making an against-the-odds comeback. Still fresh in many minds, though, was a survey by Lake, Snell, Perry and Associates Inc., disclosed in the first quarter of 2005, which found public opinion of the FDA sliding. The poll asked 1,000 people, with an error margin of plus or minus 2.5 percent, and found only 14 percent had a great deal of confidence in the FDA, while two-thirds favored an independent body to conduct a full review of the agency’s practices and procedures, with 70 percent in favor of strengthening the FDA’s collection and reporting process on drugs and devices that have been found to cause harm after approval. At the other end of the 2005, in December, came word that Woo Suk Hwang of Seoul National University had fabricated his much-hailed research (published in Science) on stem cells and cloning, which led to him lose the prestigious World Technology Award and also led to increasing public skepticism of the industry. After stripping Hwang of the prize, judges gave it to BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 11 Nadrian Seeman, of New York University, for his efforts in DNA-based nanotechnology. But regarding cash, the picture was bright, even if initial public offerings and secondary financings stayed flat, noted Steven Burrill, CEO of Burrill & Co., which operates in venture capital and merchant banking. The industry started 2005 on a “slow note,” he said, but picked up after April. BioWorld Snapshots lists 33 IPOs in 2005, with 16 in the U.S. markets, and most pricing well below hoped-for levels. In 2004, 37 IPOs were completed, with 28 in the U.S. Not only did 2005’s IPOs price low, but aftermarket performance was grim – though among the winners was Threshold Pharmaceuticals Inc. Early in the year, Threshold priced its IPO of about 5.3 million shares at $7 per share, raising about $37.3 million. The amount was much lower than the $86.25 million upper range targeted, but in early 2006, Threshold was trading at the handsome price of nearly $15. More typical of the IPO trend, though, was CardioVascular BioTherapeutics Inc., which in March raised $17.25 million by selling 1.7 million shares at $10 per each. Around the same time a year later, the stock was trading over the counter at about $5.50. The big financial gains were made, as usual, by the larger-cap firms, such as powerhouse Genentech Inc., which finished 2005 not only with news that it had submitted its biologics license application for Lucentis (ranibizumab) to treat age-related macular degeneration but also with a market cap of more than $97 billion, just above that of Amgen Inc., which also beat the $97 billion mark. Amgen made headlines, too, at year’s end, with its plan to buy the transgenic mouse firm Abgenix Inc. for $22.50 a share, or about $2.2 billion in cash. Among the hot therapeutic areas of 2005 was pulmonary arterial hypertension. Myogen Inc. finished the year with Phase III data showing its oral endothelin, ambrisentan, boosted patients’ exercise capacity, while improving a key secondary endpoint of time to clinical worsening, along with hitting several other secondary efficacy endpoints. Myogen geared up to compete with Pfizer Inc.’s Revatio – based on sildenafil, the active ingredient in Viagra – which won U.S. clearance for PAH in June, when speculators began weighing Revatio’s fate in the marketplace with Actelion Ltd.’s Tracleer (bosentan), a dual endothelin receptor antagonist and the only other approved oral therapy for PAH. In the first part of 12 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2006, Myogen signed a potential $100 million ex-U.S. deal for its PAH therapy with GlaxoSmithKline plc. Also in the mix are the strong-selling Ventavis (iloprost), an inhaled prostacyclin from CoTherix Inc., which in-licensed the compound from Schering AG in 2003. Ventavis gained approval at the end of 2004. More invasive therapies include United Therapeutics Corp.’s prostacyclin Remodulin (treprostinil), cleared in 2002 as a continuous subcutaneous infusion and later allowed as an intravenous infusion. There’s GSK’s intravenous drug, Flolan (epoprostenol), for PAH, too – which Myogen agreed to sell in the U.S., as part of the ambrisentan deal, in a provision that handily funded Myogen’s PAH sales force ahead of ambrisentan’s launch. Still pending as 2006 began was a new drug application, submitted in May by Encysive Pharmaceuticals Inc., for its Thelin (sitaxsentan) for PAH. Myogen’s news hit shares of Encysive hard, taking away 33 percent on the day Myogen made public the Phase III results. Another indication that came on strong in 2005 was hepatitis C. There the headliner was Vertex Pharmaceuticals Inc., which in May offered positive interim Phase Ib data with VX-950, its oral protease inhibitor for hepatitis C, enough to bump the stock by about 20 percent to the $13-plus range. But, by late January 2006, Vertex shares were trading at around $33.50, having appreciated a whopping 250 percent during 2005. Gathering more steam during the year was the field of Toll-like receptors, as Wall Street continued to catch the wave that began swelling about five years ago. Found on the surfaces of antigen-presenting cells, TLRs are glycoprotein molecules that recognize microbial structures and, when bound to them, trigger innate immune responses in the body. TLR-focused Coley Pharmaceuticals Inc. in August raised $96 million through an initial public offering and at the same time picked up another $10 million by way of a private placement with Pfizer, which had signed a TLR partnership with Coley in March, valued at up to $505 million. The deal gave Pfizer worldwide rights to ProMune, a Phase II TLR9 agonist for nonsmall-cell lung cancer, malignant melanoma and cutaneous T-cell lymphoma. Another firm with TLR interests, Anadys Pharmaceuticals Inc., drew the attention of Novartis AG, and the firms entered a potential $570 million deal during the summer based on the Phase I compound ANA975 and BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 13 other TLR7 oral prodrugs for chronic hepatitis C and hepatitis B viruses. Anadys got a $20 million initial license payment and another $10 million after the FDA’s acceptance of an investigational drug application, with the rest of the cash dependent on regulatory and commercial milestones. Dynavax Corp. continued work with its TLR platform, too, and in early 2006 watched its stock jump 34 percent after the company reported two-year data from a Phase II/III trial showing that its disease-modifying allergy drug, Tolamba, significantly reduced symptoms compared to placebo. Tolamba emerged from technology based on short synthetic DNA molecules designed to stimulate a Th1 immune response through the interaction of TLR9. Any story about 2005 would be incomplete without the mention again of influenza. Unlike in 2004, when fears of a vaccine shortage occupied the headlines, thanks to Chiron Corp.’s contamination screw-up at its Liverpool facility, the hysteria in 2005 boiled around avian flu, and its chance for jumping to humans. The likes of Gilead Sciences Inc. and BioCryst Pharmaceuticals Inc. also benefited from the year’s focus on the bird flu and vaccines that might work against it. Gilead’s Tamiflu (oseltamivir phosphate) is approved to treat uncomplicated influenza A and B in patients ages 1 and older, and also as a prophylactic in people 13 years or older who are at high risk during flu season. Marketed by F. Hoffmann-La Roche Ltd., Tamiflu is being investigated for use in the event of an avian flu pandemic. In December, the FDA gave approval for BioCryst to begin human studies with peramivir, its intravenous influenza neuraminidase inhibitor, which showed in preclinical studies activity against multiple strains of flu, including the H5N1 avian virus. The news caused BioCryst’s stock to jump more than 15 percent. Not all observers are convinced that the H5N1 strain will cause a pandemic, but most believe the virus will spread to some degree. Very few expect a pandemic immediately, so researchers – and investors – are gambling with time. Still, fears were strong enough that, as 2006 began, a firm such as the antisense company AVI BioPharma Inc. got a 28-percent-plus stock rise out of positive preclinical findings against H5N1 and human flu strains. Trends for the year? “I don’t know if 2005 will be remembered for this specifically, but something that is changing and is going to be more accepted, is that companies 14 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 that are doing true innovation are getting rewarded,” said Adam Noah, analyst in the San Francisco office of Merriman Curhan Ford & Co. “Maybe the investor community doesn’t see that yet, which is why the IPOs and such don’t look fantastic, but we’re seeing Phase I and preclinical deals with a lot of zeroes in them. Big pharma truly needs new drugs. If you go to less sector-specific investors, their eyes roll [at Phase I deals], but you see less and less of that, compared to a year or a year and a half ago.” Noah’s favorite example is the agreement between Arena Pharmaceuticals Inc. and Ortho-McNeil Pharmaceutical Inc., a unit of Johnson & Johnson, focused on two preclinical small molecules for Type II diabetes and other disorders. Each could bring the company $295 million in downstream milestone payments, along with a $17.5 million up-front payment, and it is entitled to receive low-double-digit royalties that would rise based on worldwide sales, if the products reach the market. In research funding, Arena will receive $4.8 million over two years. The bottom line for Arena, if two products are developed and approved, is $612.3 million, not including royalties. Even if the take is much less, “it’s still a preclinical compound that just went to Phase I a month ago,” Noah said in March 2006. “Arena went out there and found a receptor in the right place that has the appropriate characteristics for diabetes.” Arena is “going after [G-protein coupled receptors], and something like 20 to 30 percent of all approved drugs use this method,” so they’re an intelligent risk, he said. In some cases, Noah said, investors might trust the judgment of one of the partners when deciding whether to put chips on a particular bet. He cites Array BioPharma Inc.’s early stage oncology deal with Genentech, expanded in October 2005 and begun more than a year earlier. “There’s no way I can know for sure that Array can do kinase inhibition – nobody knows that,” Noah pointed out, but Genentech’s choice of Array is “almost like a biomarker for the finance market. Why would they pay someone else to make a kinase inhibitor, when they already have one of the five approved?” Genentech’s small-molecule tyrosine kinase inhibitor, Tarceva (erlotinib), partnered with OSI Pharmaceuticals Inc., first gained marketing clearance against non-small-cell lung cancer, but the once-daily tablet won approval in November for use in combination with gemcitabine as a BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 15 first-line treatment in patients with pancreatic cancer who have not received prior chemotherapy. “People are always saying, ‘This is the year of [mergers and acquisitions],’ ” Noah said. “There might be a slight uptick from year to year, but I’ve always said there are not going to be that many M&As because as long as you can outbid other pharma, why would you buy it? You make a backended deal instead.” Reminded of Amgen’s buyout of Abgenix, Noah noted “Amgen was already locked in with Abgenix,” by way of a 2002 partnership for panitumumab, a monoclonal antibody for colorectal cancer, which Amgen gained in its takeover of Immunex Corp. “I could see a lot of M&As at that level,” he allowed. But what’s more likely to continue are the creative companies, once seen as underdogs, making deals and drawing the favor of investors, Noah said, with a nod toward Amylin Pharmaceuticals Inc. "It was almost a hobby to go against Amylin for many years, because they were doing something new, and look where they are now," he said. In August, Amylin’s stock jumped more than 27 percent on positive early data from an ongoing Phase II study of its long-acting release formulation of Byetta (exenatide) in Type II diabetes patients, being developed with help from Alkermes Inc. (A twice-daily injection of Byetta, partnered with Eli Lilly and Co., was approved the spring of 2005 as an adjunct treatment for patients who failed to achieve adequate blood sugar control using metformin or sulfonylurea, or a combination of the two.) One week after the positive LAR Byetta news, Amylin, which has another approved diabetes drug, Symlin (pramlintide acetate), cleared in March 2005 for Type I and II diabetes patients for whom insulin is not working, raised $152 million in a stock sale. And Amylin, which boasts are hearty pipeline, started out 2005 by raising $176 million in a public offering. Noah said Amylin’s CEO Ginger Graham said during a recent speech, “We probably got lucky, because nobody believed us,” thus allowing Amylin to keep, and develop, its value before reaping the potential $435 million deal in the fall of 2002. Changing times will mean more such stories, he predicted. “Don’t get down on yourself because you’re not believable, because you could have the last laugh,” Noah said. ■ 16 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 The View From Wall Street Some Drug Trouble Aside, Biotech Performs In 2005 By Karen Pihl-Carey Staff Writer When a starlet makes a movie that crashes at the box office, her onceloyal fans might leave the theater fretting the $8.25 just wasted and think twice about seeing her next film. But it won’t stop them from returning to the theater altogether. In the biotech sector, the scenario is not much different. The multiple sclerosis drug Tysabri from Biogen Idec Inc. was a star of sorts in early 2005, but its withdrawal in February due to serious adverse effects helped cause a depressed public market rampant with investor doubt. By May, however, that doubt was gone and faith restored. Stocks began to rise on positive earnings from big-cap biotech companies and strong Phase III data from South San Francisco-based Genentech Inc. By mid-year, theater-goers were buying tickets again. “At the beginning of the year, the biotech market as a whole was suppressed, and I think one could look at the failure of Tysabri, when it was pulled from the market, as kind of a barometer for the sector,” said Andrew McDonald, an analyst with Think Equity Partners LLC in San Francisco. “Since that catastrophe, we saw the market rebound very strongly.” In terms of stock performance, it was a very good year. Returns over the last three years have steadily increased, he said, putting 2005 about 80 percent ahead of 2003. But 2005 fell just short of the previous year in terms of total money raised by biotech. BioWorld figures indicated the industry pulled in $20.1 billion in 2005 through public and private financings, a 3 percent drop from the $20.8 billion raised in 2004. It completed 33 initial public offerings and 59 follow-on offerings in 2005, compared to 37 and 43, respectively, for the year before. In the U.S., there were 16 biotech IPOs throughout the year, compared with 28 in 2004. The Nasdaq Biotech Index moved from 768.52 to 790.31 over the course BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 17 of 2005, up just 3 percent. BioWorld’s non-weighted stock tracker showed stocks fell about 2 percent during the year. Joel Sendek, an analyst with New York-based Lazard Freres & Co. LLC, doesn’t pay much heed to year-over-year fluctuations. “The industry has matured to the point that there isn’t really necessarily an opening or a shutting” of a public market window, he said. “There’s an opportunity for a company with a good story to finance at any time, in my opinion.” The 33 international IPOs raised a total of $1.5 billion, while the followon offerings brought in about $4.1 billion. The bulk of the money raised in 2005, however, came from private rounds and placements, accounting for $14.5 billion of the $20.1 billion figure. The rebound following the Tysabri withdrawal by Cambridge, Mass.based Biogen and Dublin, Ireland-based Elan Corp. plc came through positive earnings and clinical data by heavy-hitters such as Genentech, Amgen Inc. and Gilead Sciences Inc. “In contrast to recent years,” Sendek said, “the biotech market was very resilient, the large-cap in particular,” and that was driven by a “string of successes” at Genentech, Amgen and Gilead. “The other big driver in the sector,” McDonald said, “has been the deals, the record biobuck deals that have occurred as a result of big pharma’s pipeline loss.” In June, Anadys Pharmaceuticals Inc. entered what was hailed the largest Phase I deal in biotech history – worth up to $570 million – with Novartis Pharma AG to advance ANA975 and other Toll-like receptor 7 oral products for chronic hepatitis C and hepatitis B viruses. By the end of the year, AtheroGenics Inc. entered the largest collaborative biotech deal of the year – worth $1 billion, including a $50 million up front payment – with AstraZeneca plc to develop and commercialize its atherosclerosis drug, AGI-1067, a product that is in “an incredibly speculative Phase III,” McDonald said. But big pharma seems willing to pay high figures for biotech innovation these days. And if they don’t get what they want from partnerships, acquisitions are another option. Not only were pharmaceutical companies buying to fill their pipelines, but mid- to large-cap biotech companies used acquisitions in 2005 as a way to re-invest their cash. 18 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 In December, Amgen offered to buy Abgenix Corp. for $2.2 billion. Other acquisition of note in 2005 included Pfizer’s $1.9 billion buyout of Vicuron Pharmaceuticals Inc., completed in September. One major acquisition of 2005 involved Eyetech Pharmaceuticals Inc., which two years ago was Wall Street’s darling based on high expectations for its age-related macular degeneration product Macugen. “It’s a great story in which it was a first-in-class, first-to-market product,” McDonald said. “Unfortunately, they are competing against Genentech, and that is the one person in biotech you probably don’t want to be competing against.” Data from Genentech’s age-related macular degeneration product Lucentis “blew Macugen data right out of the water and Eyetech shares came crashing down” this year, McDonald said. It resulted in OSI Pharmaceuticals Inc.’s purchase of Eyetech for $935 million, or about $20 a share – a premium to where Eyetech was trading at the time. “The market voted with its feet and said that it was not a wise deal,” Sendek said, “and that’s why OSI’s stock underperformed in 2005. But a lot of these deals aren't done for short-term reasons,” and there may be a “logical” answer as to why OSI did what it did. But the story for Eyetech seems over. Before it faced competition from Lucentis, the company had been focusing on expanding Macugen for different indications, but it had no other products in the pipeline – a risky scenario that, no doubt, contributed to its sale, an outcome that IPO investors probably didn’t anticipate. “You might have a high flyer one year, but it could be at the bottom of the heap the next,” McDonald said. “Investors in the community really need to pay attention to what the data are saying vs. all the hype.” Tysabri was a product well-hyped by its makers, but its FDA approval based on one-year data was short-lived. The drug was pulled in February following serious cases of progressive multifocal leukoencephalopathy, an event that stunned the market but should have no long-term impact on the industry, Sendek said. “Out-of-left-field risk has always existed in biotech and will always exist,” he said. “There will always be manufacturing shut downs or unforeseen toxicity that crops up in the field that didn’t in clinical trials. That’s the BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 19 nature of the business. And I think it’s a warning that nothing’s a sure thing.” Nevertheless, analysts believe that 2006 may be the year for biotech’s small-cap companies – those with a market cap of $500 million or below. “What I’m hearing from a lot of these fund managers is they’re hiring analysts to specifically find those small-cap names where they can deploy capital,” McDonald said. In many cases, valuations of the mid- to large-cap companies are “excessive,” he added, so investors are looking for bargains instead. “These are companies that have been forgotten about,” McDonald said, “have not done a good job marketing themselves but have incredibly valuable assets in development.” A good example of that, he said, is Advanced Magnetics Inc., a company with a $190 million market cap that has an intravenous iron replacement agent, ferumoxytol, in Phase III trials for chronic kidney disease, with positive results expected by the end of 2006. The valuation gulf between small-cap and large-cap companies, Sendek said, has “never been greater than it is now.” He believes there is a great potential in 2006 for “small-cap biotech to dramatically outperform.” A pick-up in mergers and acquisitions activity, pharmaceutical companies hungry for pipelines and the fact that smallercap companies are closer to commercial success than in previous years all may conspire to “create a strong enthusiasm on the part of institutional investors,” Sendek said. Many of the expected milestones for 2006, such as a Lucentis approval and a label expansion for Avastin, have already been priced into Genentech’s stock, leaving more opportunity for investors with the smallercap companies. Other upcoming events could include the return of Tysabri to the market and the filing of a new drug application for Gilead’s triple-drug HIV regimen using Truvada and efavirenz (Sustiva, Bristol-Myers Squibb Co.). And analysts also will be watching the sales of Vancocin HCl closely, considering its maker Viropharma Inc. had the best performing stock in the market this year, Sendek said. The stock compounded six times throughout 2005, rising from $3.10 at the beginning of the year to $18.50 at the end. 20 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Vancocin is approved to treat antibiotic-associated pseudomembranous colitis caused by Clostridium difficile, and enterocolitis caused by Staphylococcus aureus. But eyes also will be on a major product that could change the way diabetes is treated forever, McDonald said. Exubera, an inhaled insulin developed by Pfizer and Nektar Therapeutics Inc. for which a decision from the FDA is expected at any time. “That’s sort of paradigm-changing going from injectable to inhaled insulin,” McDonald said. “That’s going to be a big event this year.” (Editor’s Note: Exubera received FDA approval on Jan. 27, 2006.) ■ BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 21 The View From Washington Drug Regulatory Pathway Seen As Tougher In 2005 By Aaron Lorenzo Washington Editor WASHINGTON – To many observers, 2005 brought a regulatory tightening of the belt, of sorts, with more public attention paid to product safety than in the past. Also over the course of the year, stem cell research received a congressional boost, the muddy biogeneric picture became a little clearer, and drug makers scored with liability protection for flu vaccine R&D. The heightened safety consciousness, of course, represents a reaction to the now infamous painkiller Vioxx, and the FDA increased its number of black box warnings for products correspondingly. The agency also began to talk about a safety data sharing arrangement with the Centers for Medicare and Medicaid Services. At the same time, drug companies vowed to disclose more clinical trial information than previously, in an attempt at transparency. But from Capitol Hill and consumer watchdog groups came calls for a new safety oversight department, and while that clamoring has not yet died, the FDA preemptively created its own Drug Safety Oversight Board to independently oversee such issues. That was lauded by the Biotechnology Industry Organization, the Washington-based trade association that lobbied against “draconian measures” from Congress in reaction to drug safety concerns, said its president and CEO, Jim Greenwood. The fact that the FDA’s “solution” is housed within the agency’s Center for Drug Evaluation and Research (CDER) did little to silence critics. Some saw the agency’s reputation further blemished in regard to the market withdrawal of Tysabri early in 2005. Heralded just months before as the next great multiple sclerosis treatment, and approved early on one-year pivotal trial data, it soon became linked with a rare but fatal disease that prompte its removal. The FDA’s increased safety efforts might partly explain the downturn in approvals seen last year and the growth of a risk-averse climate at the agency. Those matters could be setting the table as “a prelude” to this year when negotiations to renew the Prescription Drug User Fee Act (PDUFA) get under way in earnest, said Michael Werner, who heads The Werner Group 22 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 consulting firm in Washington. “Within the rubric of PDUFA negotiations, there will be discussions about why approvals are down,” he said, with drug safety issues playing a prominent background role. He called the negotiation phase, which began with a public hearing last fall, “an obvious vehicle for Congress to get involved” and an opportunity for agency and industry representatives to sit at the same table. “There will be a lot of discussion and negotiation this year about what PDUFA will be and what it will look like,” added Greenwood, the former congressman who in his first year leading BIO brought on board several Washington insiders with previous Capitol Hill and FDA experience to fill advocacy roles. Concerns over leadership at the FDA came to a head when Lester Crawford abruptly resigned in September as commissioner, just months after receiving Senate confirmation for the post. Crawford had been acting commissioner for almost two years. Into his place stepped Andrew von Eschenbach, who had been in charge of the National Cancer Institute. Initially he announced his intention to maintain both positions, although he relinquished that stance and temporarily gave up his NCI role to solely head the FDA on an interim basis. Many observers expect him to be friendly to drug makers, given his oncology background, and while Greenwood conceded that the agency’s leadership “is not settled” in the absence of a confirmed commissioner, he praised von Eschenbach as “an advocate for patients” and “an ally of patient groups.” Now that von Eschenbach is settling in, Werner said he senses stability at the agency, which will help in the FDA’s dealings with Congress. (Editor’s Note: In March 2006, President Bush officially nominated von Eschenbach to head the FDA.) Observers continue to wait on official FDA guidance for regulating follow-on biologics, the so-called biogenerics many pioneer companies oppose because of manufacturing equivalency issues, but the agency has yet to finalize its approach. It’s been suggested that the matter be handled on a case-by-case basis, an approach that’s beginning to take shape in the European Union, where regulatory authorities gave a favorable opinion to the growth hormone product Omnitrope shortly after the New Year. “I think this will be a field that moves slowly,” Werner said, noting that the FDA is expected to let European regulators take the lead. He added that BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 23 while “pressure is going to continue to build” on the FDA, the agency signaled that clinical studies would be necessary in many circumstances, especially with proteins more complex than growth hormone. Because generic companies could have to pay for clinical trial work and marketing, biogenerics might not provide much in the way of cost savings for consumers in the end. Stem cell advocacy increased in Congress, and at the end of the year, President Bush signed a bill to fund further research into obtaining cells from umbilical cord blood, an uncontroversial source. Legislation to increase federal funding for embryonic stem cells is not likely to get the president’s blessing, but after the Castle-Degette bill passed in the House to allow that funding, it got a significant endorsement from Senate Majority Leader Bill Frist (R-Tenn.). His swing away from President Bush’s policy on the matter signaled a shift, and Greenwood praised Frist and his Senate colleague Orrin Hatch (RUtah) for their efforts in drumming up support and going against the administration. While Bush has said he’d use his veto powers on stem cell issues, Greenwood nonetheless stressed that “it’s important to push the issue anyway.” The industry also scored on Capitol Hill with new legislation to fund bird flu prevention efforts. After President Bush called for a $7.1 billion package in the pandemic fight, a sizable portion of which could go toward drug makers developing countermeasures, the measure cleared both houses of Congress just before their session ended. In the context of the same bill came a wide-reaching liability shield to protect those drug makers from claims of negligence. Greenwood, who called the pandemic flu bill’s passage critical to “building the infrastructure” for vaccine production using improvements on old egg-based methods and new cell-based technologies, added that it was an equally “good sign” that Congress moved on the liability protection. “You can’t expect companies to respond in crisis mode to a potential emerency,” Greenwood said, and push them to drop all other activities if they expect to be subjected to “horrific levels of liability.” ■ 24 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 The View From The Lab Bench Huge Stem Cell Scandal; HighThroughput Epigenetics Work By Anette Breindl Science Editor South Korean researcher Woo-Suk Hwang made Science magazine’s Top 10 Breakthroughs of the Year list in 2004 for the first cloning of a human embryo. His 2005 report on the first cloning of a dog, “Snuppy,” earned the designation of “Invention of the Year” from Time magazine. But things turned. If there were an award for starkest reversal of fortune, Hwang would get that, too. Neither the human nor the dog cloning paper had been retracted by the end of 2005. But questions about both inevitably arose as another paper, in which Hwang’s group claimed to have made patient-specific embryonic stem cell lines with a high enough efficiency to be useful for clinical applications, went from breakthrough to burlesque, with revelations about ethics violations in procuring the eggs, followed by accusations that the whole omelet was rotten. The data had been faked. (Editor’s Note: In January 2006, an investigation panel set up by Seoul National University confirmed that Hwang and his team had created data to support their 2005 claim to have made patient-specific stem cell lines, as well as their 2004 report of having cloned the first human embryo. Testing of Snuppy, however, confirmed that the dog was indeed a clone.) But as Michael West, chief scientific officer, chairman and president at Advanced Cell Technology Inc., of Worcester, Mass., told BioWorld Today while discussing the Hwang case, “for every forger, there are 99 dedicated and honest people out there.” What follows are some, though not all, of the top discoveries of 2005 – hopefully, no retractions will be necessary. Cancer With more than half of all genetic alterations in some cancers stemming from epigenetic mechanisms, such as methylation and acetylation, epigenetic research was an active area in 2005, and the year ended with a call for a “Human Epigenome Project” in the Dec. 15, 2005, issue of Cancer Research. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 25 One reason epigenetic research is gaining speed is that methodologies for epigenetic studies are becoming high-throughput enough to make whole-genome studies a realistic option. One example is a study published in Cell in January 2005, which used whole-genome tiling arrays for analyzing certain methyl, as well as acetyl, marks in both human cancer cell lines and human fibroblasts. The researchers studied methylation of one specific lysine, lysine 4, across a large region of the genome; many of the proteins that have a methylated lysine 4 are associated with cancer in some way. Lead author Bradley Bernstein told BioWorld Today that “the tiling arrays allow the analysis to proceed in a very unbiased fashion,” added that “this technique opens up another avenue for identifying functionally important regions of the genome.” Scientists also learned how to methylate DNA in the lab, as reported in the Nov. 27, 2005, early online edition of Nature Chemical Biology. The genetics of cancer yielded new surprises in 2005. Several studies investigated the mechanisms and functions of the tumor suppressor gene p53. In July, a paper in the Proceedings of the National Academy of Sciences, which could be summed up “never trust a test tube,” reported that in vivo, it is not p53 protein itself that is crucial for determining whether a cell will be normal or cancerous, but the ration of two of its regulator proteins, MDM2 and MDMX. Also in July, a study published in Neuron reported that overactive p53 might play a role in neurodegenerative disorders. Evolution Science magazine’s breakthrough of the year 2005 is not likely to be debunked within a year’s time. The magazine picked “Evolution in Action” as last year’s winner. The magazine said in its explanation that “at some level every discovery in biology and medicine rests on [evolution].” Each year, it said, “researchers worldwide discover enough extraordinary findings tied to evolutionary thinking to fill a book many times as thick as all of Darwin’s works put together.” The editorial staff at Science said that “2005 stands out as a banner year for uncovering the intricacies of how evolution actually proceeds.” One such finding, published in the Dec. 4, 2005, early online edition of Nature, presented evidence that at least in polio viruses, selection can occur at the population level, rather than being directed at individual variants. Senior author 26 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Raul Andino said that his paper demonstrated the need for population diversity of RNA viruses for successful infection to occur and that the reason diversity is necessary is that different types of mutants need to cooperate for successful infection, not so that the “best” mutant can propagate in winner-take-all fashion. Raul said that though it is easiest to see population level selection in RNA viruses, with their high mutation rate and short generation time, the mechanism also operates on higher organisms. Genomics On Oct. 26, 2005, an international consortium consisting of researchers from academic centers, non-profit biomedical research groups and private companies in the U.S., Canada, China, Japan, Nigeria and the UK completed a haplotype map of the human genome for almost 3 million single nucleotide polymorphisms, or SNPs, in six geographically distinct populations. Francis Collins, director of the National Human Genome Research Institute, said at a press conference that for disease association studies the HapMap “may ultimately prove more powerful” than the map of the human genome that was published in 2003. The human genome project published a consensus sequence of DNA – that is, the bases everyone has in common. But Collins noted “variety is the spice of life,” and it is in fact the bases that differ in the population that hold the most promise for determining genetic contributions to disease. With the Human Genome and the HapMap completed, the next largescale sequencing project, announced on Dec. 13, 2005, is The Cancer Genome Atlas, a joint project of the National Cancer Institute and the National Human Genome Research Institute. In a three-year pilot phase, researchers intend to “assess the feasibility of a full-scale effort to systematically explore the entire spectrum of genomic changes involved in human cancer,” according to the project’s website. And man’s best friend was not just cloned in 2005, but sequenced as well. In December an international team announced the publication of the genome sequence of the dog in Nature. Infectious Disease Avian flu continued to be under sharp watch by the World Health Organization. In 2005, the virus left its native Southeast Asia and spread to BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 27 Turkey via migratory birds. (Editor's Note: In January 2006, the WHO confirmed its first cases of human H5N1 infection in Turkey.) A number of academic labs and companies began or continued work on avian flu vaccines. Meanwhile, animal vaccination was suggested as an alternative to bring the virus under control in birds, where a pandemic is well under way. Several countries have undertaken large-scale culling – a euphemism for the killing of infected bird populations, and many experts believe that Hong Kong’s massive culling when the first human infections were reported there in 1997 has prevented a pandemic to date. But in a May editorial in Nature, researchers at the St. Jude’s Children’s Research Hospital in Memphis, Tenn., suggested that vaccination needs to move up the priority list. They wrote, “A global strategy for preventing pandemics at their source – in the animals, mostly poultry, that carry the virus – has received relatively little attention.” They said the goal “must be to reduce the virus load in ducks below the transmissible level,” and added it “is probably the approach that has the best chance of reducing the inevitability of H5N1 acquiring consistent human-to-human transmission.” A major advantage of animal vaccination is not scientific, but economic. Poultry is often a major source of income generation for rural farmers in Southeast Asia, especially in Vietnam, the country with the most confirmed cases of H5N1. In other words, faced with an infected flock and the choice to kill all birds and lose her livelihood or let them live and face a small chance of becoming infected with H5N1 – well, for the rural farmer, the decision is not easy. In October researchers announced they had resurrected the virus that caused the 1918 “Spanish flu” pandemic and sequenced its polymerase genes that form its basic replication machinery. Scientists hoped their findings will help them understand why some forms of virus are more dangerous than others, as well as aid in molecular-based surveillance of viral strains circulating in the wild. One thing already apparent from the sequence data is that the 1918 strain was not a mix of bird and human flu virus, as was the case for the strains that caused 20th century’s two other pandemics, but was an entirely bird-derived virus that adapted to humans, either directly or via an intermittent host. The research was published in the 28 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Oct. 6, 2005, issue of Nature and the next day’s issue of Science. The 2005 Nobel Prize in physiology or medicine was awarded for a discovery concerning infectious disease: Barry Marshall, of the University of Western Australia’s Helicobacter pylori Research Laboratory in Nedlands, Australia, and Robin Warren, a pathologist retired from the Perth Royal hospital in Australia, received the prize for their discovery of “the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.” Neuroscience The prion hypothesis – the idea that infectious diseases, in particular spongiform encephalitises like Creutzfeldt-Jacobs disease, mad cow disease and scrapie, can be transmitted by a protein rather than DNA or RNA – came one step closer to being proved last year. In the April 22, 2005, issue of Cell, researchers reported they were able to amplify abnormally folded prion proteins in a test tube until, homeopathy-like, the concentration of original material was too low to cause infection. Very unlike homeopathy, though, the method generated plenty of artificial prion protein, and the scientists were able to cause scrapie in a previously healthy hamster by injecting the animal with those artificial proteins. The experiments do not provide final proof for the prion hypothesis, which would require a recombinant protein to infect a previously healthy animal. But they are only one step away. Some of the fiercest critics of the prion hypothesis remain unconvinced, though. On Oct. 21, they published research on the infectiousness of different spongiform encephalitis strains in Science that was incompatible with the prion hypothesis but consistent with the idea that the infectious agent is a virus. Their explanation for the Cell paper? Contamination. Stem Cells Stem cells were a highly active research field in 2005. The belief that they are a cure-all, though fairly widespread in the scientific community, continues to await clinical confirmation. Many major scientific stem cell findings last year related to stem cell sources rather than cures: In the February 2005 issue of Nature Medicine, researchers showed the culturing methods used to grow most embryonic stem cell lines have led to a contamination of those lines with acidic sugars that can lead to an BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 29 immune reaction in humans. At least one commercially available serum replacement also contained such sugars. The scientists suggested that to be sure contaminations do not ultimately reach the clinic, it might be best to start afresh with new embryonic stem cell lines. Current federal regulations, of course, prohibit the funding of research on or with new embryonic cell lines. Adult stem cells, which have none of the ethical problems associated with embryonic stem cells, are sometime paraded by critics as proof that embryonic stem cell research is unnecessary. Unfortunately, adult stem cells have nowhere near the versatility of embryonic ones. The May 17, 2005, issue of the Journal of Experimental Medicine contained a study showing that blood stem cells do not form neurons when transplanted into the brain after an injury. The paper was an extension of previous research that had demonstrated that in the normal brain transplanted blood stem cells do not form brain cells in appreciable numbers. In October, scientists reported they had made embryonic stem cells by a technique that does not allow the development of an embryo. Some researchers celebrated the advance as providing embryonic stem cells without the ethical issues, though The New York Times quoted one researcher as saying, “If you believe a fertilized egg is a human being, you would purposely be getting a defective person,” adding, “I honestly don’t understand the moral high ground.” Although the discovery originally came in 1961, the award came in 2005. In September, the Lasker Foundation announced that the 2005 Albert Lasker Award for Basic Medical Research was being shared by Ernest McCulloch and James Till, both of the University of Toronto Ontario Cancer Institute in Canada, for “ingenious experiments that first identified a stem cell – the blood-forming stem cell – which set the stage for all current research on adult and embryonic stem cells.” This year is almost sure to bring new findings on avian flu, and given the large-scale cancer efforts initiated near the end of 2005, significant advances in understanding of cancer also are likely. Though given the stem cell scandal following 2004’s many honors, it is wise to keep in mind the saying attributed to Nobel prize winning physicist Nils Bohr: Prediction is very difficult, especially if it’s about the future. ■ 30 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 BIOWORLD ® F I N A N C I A L D A T A Discerning Market, Caution Drove Trends In Financing By Jennifer Boggs Staff Writer Despite a discriminating public market and increasing competition in the venture capital arena, funding in biotech held strong in 2005, as money continued to flow steadily into the sector. The total $20.1 billion raised during the year marked a slight – about 3 percent – from the $20.8 billion brought in during 2004. For some, the year was a boon. Certain public companies were able to capitalize on clinical data and raise big money - such as Panacos Pharmaceuticals Inc., which brought in $86 million six weeks after reporting promising Phase II results with its lead drug, PA-457 in HIV. For private firms, those with drugs in late-stage development generally met with the most fund-raising success. But the public markets cast a particular dilemma upon smaller but latestage firms. They faced the choice of entering a public market giving them meager valuations, or attempting to squeeze additional funds from venture capital investors. During the year, a total of 33 biotech companies priced initial public offerings, only four fewer than in 2004. But those offerings generally drew less money than expected. In 2005, a typical IPO story looked a lot like the tale of Advanced Life Sciences. In August it priced its IPO at $32 million, but it had hoped to raise $86 million when it filed for the offering in April. It cut expectations a few months later, to $42 million, when setting a price range of 6.4 million shares between $8 and $9. When it did price, each share was valued at $5. Altogether, biotech raised $1.5 billion in initial public offerings, averaging about $45.5 million each. The 37 IPOs priced in 2004 brought in a total of $2 billion, and averaged about $10 million more, at $55.25 million apiece. As of Dec. 31, 1 1 companies had pending IPOs, but the low valuations in 2005 were enough to prompt a number of firms to reconsider, and more than a dozen biotech companies withdrew their initial offerings. There also is a third option – mergers and acquisitions – and some withdrew their IPOs in 2005 to go that route, such as Salmedix Inc. The company agreed to an acquisition by Cephalon Inc. in May. That deal was valued at $160 million. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 33 “One of the things that stood out most in 2005 was the sharp increase in M&A activity in the space,” said analyst Jason Kantor of RBC Capital Markets in San Francisco, adding that the rise initially was fueled by an early year flurry of acquisitions involving private companies “that for one reason or another, didn't feel like they had access to good capital.” According to BioWorld Snapshots, there were a total of 179 completed mergers and acquisitions involving biotech firms in 2005, up nearly 18 percent from the 152 deals completed in 2004. The biggest deal of the year came in late October, when pharma giant Novartis AG offered $5.1 billion to buy Chiron Inc., indicating that “in public markets, as well, people are eager to see more M&A,” Kantor said, adding, “You’ve got other companies like Gilead and Genentech and Biogen Idec out there saying that they're shopping around for acquisitions.” VCs Favor Clinical-Stage Profiles For established public firms, money was available – the number of public firms that raised money increased last year from 2004 – though the average follow-on priced about $10 million below the 2004 average. According to BioWorld, a total of 59 offerings raised $4.1 billion, averaging $69.1 million apiece, compared to the 43 public offerings in 2004 that raised $3.4 billion and averaged $79.3 million each. But the venture capital industry continued to provide strong support for biotechnology. There was a steady stream of funds flowing into the life sciences sector in 2005. According to the 2005 MoneyTree venture capital survey, conducted by PriceWaterhouseCoopers, Thomson Venture Economics and the National Venture Capital Association (NVCA), the amount of money being invested in late-stage companies in all sectors increased for the fourth year in a row. About 45 percent of private investments went to latestage firms, i.e. companies that have products in the clinic. “That’s what investors are looking for,” said Philippe Chambon, managing director with New York-based New Leaf Venture Partners, which invests primarily in companies with products in clinical development. “They want late-stage, from a risk-profile standpoint.” Or they want reduced risk in general – firms focusing on one thing and doing it well. “What was interesting to me is that we also started to see a more consistent emergence” of single-product companies, which is “really a bit more 34 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 akin to the medical device world,” Chambon said. Those companies focus on a single opportunity “with the aim of developing that product to a certain endpoint and then selling it to another company.” One of New Leaf’s portfolio companies is a good example. Tioga Pharmaceuticals Inc. was founded by investment firm Forward Ventures in mid-2005 after gaining rights to asimadoline, a Phase II-stage compound for gastrointestinal diseases from Merck KGaA. Tioga’s executives have said that all the company’s resources are being put toward the development of asimadoline. This single-product trend is “a good thing for the biopharma sector,” Chambon said. Overall, biotechnology VC funding was down slightly from 2004 numbers, but full-year figures from the 2005 MoneyTree venture capital survey showed a slight increase in overall venture financing in 2005, with the entire life sciences segment – including the biotechnology and medical device industries – capturing roughly 30 percent of VC money. Two biomedical firms made it onto the MoneyTree list of the top 10 largest venture financings in 2005: Seattlebased Light Sciences Oncology Inc., which closed a $67 million Series A round in December, and South San Francisco-based Portola Pharmaceuticals Inc., which in November added $46 million in its Series B. According to the survey, nearly $3.9 billion was invested in biotechnology in the U.S. last year, down from about $4.1 billion in 2004. BioWorld’s figures, which include financings from around the globe, reported a total of $4.8 billion raised by private companies in 2005, compared to $4.9 billion in 2004. Despite the slight drop, the past two years have still been “at record levels, historically, for biotech financing, which long-term is very promising for the sector,” said Tracy Lefteroff, global managing partner at PWC’s Venture Capital & Private Equity Practice. Whether that healthy fund raising will continue remains to be seen, though the first month of 2006 started off on the right foot. Altus Pharmaceuticals Inc. raised $105 million in an IPO, and Arena Pharmaceuticals Inc. priced a follow-on offering, selling 9.75 million shares at $16.90 apiece and raising $164.8 million for a Phase III trial with its lead obesity drug. “I think it’s going to continue,” PWC’s Lefteroff said of the financing trend. ■ BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 35 36 585.7 406.3 744.9 1,736.9 Public offerings Private biotechs Public/other Total ($M) 2,137.1 701.1 636.6 799.4 Feb. 1,297.3 717.0 276.4 303.9 Mar. 562.7 309.2 182.4 71.2 Apr. 957.0 202.6 61 1.1 143.3 May 2,835.6 1,796.7 439.7 599.6 June 3,047.2 2,393.9 262.4 390.9 July 570.9 361.6 491.0 Sept. 266.3 588.8 527.8 Oct. 503.4 293.7 562.7 Nov. 755.8 314.9 373.8 Dec. 9,726.41 4,808.88 5,579.57 Total ($M) 1,930.6 1,423.4 1,382.8 1,359.7 1,444.5 20,1 14.86 764.7 435.4 730.5 Aug. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2005 rights offerings, standard private placements, PIPE financings and institutional offerings of registered stock. Public/other = Other financings of public companies, including loans, bridge financings, exercises of warrants, debt offerings, Private biotechs = Financing of private firms. Public offerings = Initial, follow-on. Notes: Jan. Type of financing Money Raised By Biotechnology Companies In 2005: January – December 2005 Initial Public Offerings Company (Symbol) Date Filed Date Comm. Shares/ Units (M) Narhex Life Sciences Ltd. (Australia; ASX:NLS) 10/24/04 1/12/05 66.9S ViaCell Inc. (VIAC) 4/5/04 1/21/05 Favrille Inc. (FVRL) 4/8/04 Icagen Inc. (ICGN) Price Shares Out (M) Lead, Other Underwriters Gross (M) PostOffering Market Cap (M)@ A$0.20 161.4 Montagu Stockbrokers A$13.4 ($10.4) A$32.3 8.625S $7 37.20 Credit Suisse First Boston $60.38 $260.4 UBS Investment Bank (co-lead) Lazard Freres & Co. Leerink Swann & Co. 2/2/05 6S $7 20.02 Bear, Stearns & Co. CIBC World Markets Needham & Co. A.G. Edwards & Sons 4/8/04 2/3/05 5.1S $8 21.54 UBS Investment Bank $40.8 JP Morgan Securities (co-lead) CIBC World Markets Intercell AG (Austria; ATX:ICLL) 2/14/05 2/28/05 9.49S €5.5 33.01 Goldman Sachs Lehman Brothers Bank Vontobel DZ BANK Erste Bank €52.2 ($68.7) €181.6 MediciNova Inc. (OSE:4875) 10/1/04 2/8/05 31.57S Y400 98.85 ($3.88) Daiwa Securities SMBC $122.5 $383.5 Paion AG (Germany; FSE:PA8G) 1/24/05 2/1 1/05 5S €8 15.76 UBS Investment Bank Dresdner Kleinwort Wasserstein (co-lead) Landesbank €40 ($52.7) €126.1 Threshold Pharmaceuticals Inc. (THLD) 4/9/04 2/4/05 5.333S $7 29.25 Banc of America $37.33 CIBC World Markets (co-lead) Lazard Freres & Co. William Blair & Co. 2/17/05 3/4/05 16.4S £1.28 55.56 Nomura International JANUARY FEBRUARY $42 $140.1 $172.3 $204.8 MARCH Ardana plc (UK; LSE:ARA) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 £21 ($40.5) £71.1 37 2005 Initial Public Offerings (Continued) Company (Symbol) Date Filed Date Comm. Shares/ Units (M) Price Shares Out (M) Lead, Other Underwriters Aspreva Pharmaceuticals Corp. (Canada; ASPV; TSE:ASV) 1/24/05 3/3/05 8.28S CardioVascular BioTherapeutics Inc. (OTC BB:CVBT) 9/27/04 Gross (M) $1 1 34.03 Merrill Lynch & Co. $91.1 Banc of America (co-lead) Pacific Growth Equities BMO Nesbitt Burns $374.3 3/14/05 1.725S $10 122.8 First Dunbar Securities $1,228.0 2/17/05 4/6/05 4.167S C$12 28.69 RBC Dominion Securities C$50 National Bank Financial ($40.7) (co-lead) HSBC Securities BMO Nesbitt Burns CIBC World Markets GMP Securities Loewen, McCutcheon Arpida Ltd. (Switzerland; SWX:ARPN) 4/1 1/05 5/4/05 5.4S CHF18 16.37 Deutsche Bank Julius Baer, Lombard Odier Darier Hentsch Swissfirst CHF97.2 CHF294.7 ($80.7) Galapagos NV (Belgium; Euronext:GLPG) 4/15/05 5/5/05 3.147S €7 9.17 KBC Securities Kempen & Co. (co-lead) Fortis Bank €22 ($28.1) Devgen NV (Belgium; Euronext:DEVG) 5/20/05 6/7/05 4.5S €7.5 13.86 KBC Securities Code Securities Bank Degroof €33.7 €104 ($40.2) ($124) Gentium SpA (Italy; AMEX:GNT) 1/24/05 6/16/05 2.7S $9 8.00 Maxim Group $24.3 I-Bankers Securities (co-lead) $72.0 ProStrakan Group plc (UK; LSE:PSK) 5/19/05 6/10/05 £1 186.0 Morgan Stanley & Co. £40 Credit Suisse First Boston ($72.9) Code Securities £186 ($339) $17.25 PostOffering Market Cap (M)@ APRIL Atrium Biotechnologies Inc. (Canada; TSE:ATB) C$344.3 MAY €64.2 JUNE 38 40S BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Initial Public Offerings (Continued) Company (Symbol) Date Filed Date Comm. Shares/ Units (M) Price Shares Out (M) Lead, Other Underwriters Gross (M) PostOffering Market Cap (M)@ TopoTarget A/S (Denmark; CSE:TOPO) 5/30/05 6/10/05 1 1.5S DKK 22.5 39.93 ABN AMRO Rothschild Danske Markets Handelsbanken Capital DKK259 DKK898 ($41.5) ($144) XenoPort Inc. (XNPT) 1/19/05 6/2/05 5S $10.5 19.23 Morgan Stanley & Co. $52.5 $201.9 Deutsche Bank Securities (co-lead) Pacific Growth Equities Lazard Freres & Co. 7/5/05 7/27/05 36S A$0.25 128.8 Lodge Corporate Services Advanced Life Sciences Holdings Inc. (ADLS) 4/28/05 8/4/05 6.4S $5 17.83 C.E. Unterberg, Towbin $32 ThinkEquity Partners (co-lead) Merriman Curhan Ford & Co. $89.2 Coley Pharmaceutical Group Inc. (COLY) 4/20/05 8/10/05 6.9S $16 25.70 Merrill Lynch & Co. $1 10.4 JP Morgan Securities (co-lead) Lazard Freres & Co. Leerink Swann & Co. $41 1.2 Avalon Pharmaceuticals Inc. (AVRX) 5/4/05 9/29/05 2.75S $10.50 8.40 W.R. Hambrecht + Co. $28.88 Legg Mason Wood Walker Susquehanna Financial $88.2 Genomic Health Inc. (GHDX) 7/15/05 9/29/05 5.017S $12 24.37 JP Morgan Securities $60.2 Lehman Brothers (co-lead) Piper Jaffray & Co. Thomas Weisel Partners JMP Securities $292.4 Sunesis Pharmaceuticals Inc. (SNSS) 12/23/04 9/26/05 6S $7 21.46 Lehman Brothers $42 SG Cowen & Co. (co-lead) Needham & Co. $150.2 JULY EvoGenix Ltd. (Australia; ASX:EGX) A$9 ($6.85) A$32.2 AUGUST SEPTEMBER BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 39 2005 Initial Public Offerings (Continued) Company (Symbol) Date Filed Date Comm. Accentia Biopharmaceuticals Inc. (ABPI) 2/1 1/05 Can-Fite BioPharma Ltd. (Israel; TEL:CFBI) Jerini AG (Germany; FSE:JI4) Shares/ Units (M) Price Shares Out (M) Lead, Other Underwriters Gross (M) PostOffering Market Cap (M)@ 10/28/05 2.4S $8 28.87 Jefferies & Co. Ferris, Baker Watts Stifel, Nicolaus & Co. GunnAllen Financial $19.2 $231.0 9/26/05 10/5/05 NIS337 128.9 ($73) I.B.I Poalim Apex Mutavim D.I.M. NIS45 ($10) NIS160 ($35) 10/10/05 10/31/05 15.5S €3.20 48.95 Credit Suisse First Boston €49.6 Deutsche Bank (co-lead) ($59.6) Fortis Bank West LB €156.6 Biotec Pharmacon ASA (Norway; OSE: BIOTEC) 9/30/05 1 1/4/05 3.922S NOK 24.50 21.49 DnB NOR Bank ASA NOK527 CombinatoRx Inc. (CRXX) 12/13/04 1 1/9/05 6.9S $7 23.22 SG Cowen & Co. $48.3 Pacific Growth Equities (co-lead) Lazard Capital Markets A.G. Edwards ExonHit Therapeutics SA (France; Euronext:ALEHT) 10/18/05 1 1/16/05 2.71S €2.89 21.97 Société Générale €7.8 ($9.3) €63.5 BioAlliance Pharma SA (France; Euronext:BIO) 1 1/17/05 12/7/05 2.256S €13.30 8.27 Bryan Garnier & Co. ING Securities (co-lead) €30 ($35.5) €1 10.0 Somaxon Pharmaceuticals Inc. (SOMX) 10/7/05 12/15/05 5S $1 1 Morgan Stanley & Co. $55 JP Morgan Securities (co-lead) Piper Jaffray & Co. Thomas Weisel Partners OCTOBER 0.133U NOVEMBER NOK96 ($14.4) $162.5 DECEMBER 40 18.03 $198.3 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Initial Public Offerings (Continued) Notes: * All totals inlcude the sale of shares (or units) to satisfy overallotment options, in full or in part, where applicable. @ Market capitalization calculated is based on the offering price. Foreign currency was converted to U.S. dollars based on the exchange rate at the time of the offering. AMEX = American Stock Exchange; ASX = Australian Stock Exchange; ATX = Austrian Stock Exchange; CSE = Copenhagen Stock Exchange; FSE = Frankfurt Stock Exchange; LSE = London Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; SWX = Swiss Stock Exchange; TEL = Tel Aviv Stock Exchange; TSE = Toronto Stock Exchange. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 41 2005 Follow-On Offerings Company (Symbol) Date Filed Date Comm. Shares/ Units (M) Price Shares Out (M) Lead, Other Underwriters Gross (M) PostOffering Market Cap (M)@ Amylin Pharmaceuticals Inc. (AMLN) 12/1 1/03 1/21/05 9.2S $22 103.7 Morgan Stanley & Co. $202.4 Goldman, Sachs & Co. (co-lead) Banc of America Securities JP Morgan Securities Wachovia Capital Markets $2,281.4 ISTA Pharmaceuticals Inc. (ISTA) 4/23/04 1/20/05 6.325S $8.88 25.70 Banc of America Securities $56.2 Thomas Weisel Partners (co-lead) Lazard Freres & Co. C.E. Unterberg, Towbin $228.2 La Jolla Pharmaceutical Co. (LJPC) 1 1/26/02 1/28/05 12.25S $1.40 73.76 Pacific Growth Equities $103.3 Martek Biosciences Corp. (MATK) 5/21/04 1/21/05 1.757S $49.10 31.26 Citigroup $86.3 Adams Harkness (co-lead) Needham & Co. First Albany Capital D.A. Davidson & Co. $1,534.8 Telik Inc. (TELK) 4/9/04 1/28/05 8.05S $18.75 51.88 UBS Investment Bank JP Morgan Securities Lehman Brothers $972.8 Zonagen Inc. (ZONA) 10/20/04 1/27/05 5.06S $4 10.05 Punk, Ziegel & Co. $20.24 WR Hambrecht + Co. (co-lead) $40.2 Arena Pharmaceuticals Inc. (ARNA) 5/20/04 2/1/05 8.625S $6 35.20 CIBC World Markets $51.75 Piper Jaffray & Co. (co-lead) Needham & Co. Granite Financial Group Morgan Joseph & Co. $21 1.2 Barrier Therapeutics Inc. (BTRX) 1/24/05 2/10/05 2S $19.50 23.89 Morgan Stanley & Co. Pacific Growth Equities JP Morgan Securities $465.9 JANUARY $17.15 $151.0 FEBRUARY 42 $39 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Follow-On Offerings (Continued) Company Date (Symbol) Filed Date Comm. Shares/ Units (M) Price Shares Out (M) Lead, Other Underwriters Gross (M) PostOffering Market Cap (M)@ Bioenvision Inc. (BIVN) 10/25/04 2/3/05 7.5S $8 40.42 JP Morgan Securities $60 UBS Investment Bank (co-lead) CIBC World Markets Friedman, Billings, Ramsey $323.4 CoTherix Inc. (CTRX) 1/12/05 2/10/05 4.25S $8.90 23.89 CIBC World Markets $37.83 Piper Jaffray & Co. (co-lead) Needham & Co. Thomas Weisel Partners $210.4 Neose Technologies Inc. (NTEC) 2/7/05 2/18/05 8.05S $4 32.78 UBS Investment Bank JP Morgan Securities Jefferies & Co. $131.1 Northfield Laboratories Inc. (NFLD)12 12/23/04 2/4/05 5.175S $15 26.73 UBS Investment Bank $77.63 SG Cowen & Co. (co-lead) Harris Nesbitt Nuvelo Inc. (NUVO) 1/24/05 2/2/05 9.775S $7.50 42.01 UBS Investment Bank $73.31 $315.0 Deutsche Bank Securities (co-lead) CIBC World Markets Needham & Co. Tercica Inc. (TRCA) 1/21/05 2/8/05 6.9S $8 31.50 Lehman Brothers $55.2 SG Cowen & Co. (co-lead) Robert W. Baird & Co. Friedman, Billings, Ramsey Harris Nesbitt $252.0 Cardiome Pharma Corp. (Canada; CRME) 3/1/05 3/18/05 9.775S $6 50.82 UBS Investment Bank $58.65 CIBC World Markets (co-lead) GMP Securities Leerink Swann & Co. First Associates Investments Orion Securities $304.9 Neurochem Inc. (Canada; NRMX) 2/23/05 3/4/05 4S $15.30 34.41 UBS Investment Bank CIBC World Markets Piper Jaffray & Co. Desjardins Securities Wells Fargo Securities BMO Nesbitt Burns Fortis Securities LLC $526.5 Vivus Inc. (VVUS) 12/22/04 3/10/05 6.25S $3.40 SG Cowen & Co. $21.25 $151.2 Wachovia Capital Markets (co-lead) $32.2 $401.0 MARCH BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 44.47 $61.2 43 2005 Follow-On Offerings (Continued) Company (Symbol) Date Filed Date Comm. Shares/ Units (M) Price Shares Out (M) Lead, Other Underwriters Gross (M) PostOffering Market Cap (M)@ 5/26/04 4/1/05 2S $15.25 19.28 CIBC World Markets $30.5 UBS Investment Bank (co-lead) $294.0 4/18/05 5/25/05 3.478S $12.25 13.43 CIBC World Markets $42.6 Thomas Weisel Partners William Blair & Co. $164.6 CV Therapeutics Inc. (CVTX) 6/22/05 6/29/05 8.35S $21.60 44.45 Lehman Brothers $180.4 Merrill Lynch & Co. (co-lead) Piper Jaffray & Co. SG Cowen & Co. First Albany Capital $960.1 Progenics Pharmaceuticals Inc. (PGNX) 5/26/04 6/10/05 1.53S $19.25 20.81 UBS Investment Bank $29.5 $400.6 Vertex Pharmaceuticals Inc. (VRTX) 4/1/05 6/7/05 13.51S $13 94.71 Merrill Lynch JP Morgan Securities UBS Securities $175.6 $1,231.2 BioMarin Pharmaceutical Inc. (BMRN) 12/23/02 7/14/05 8.5S $7.05 73.24 Merrill Lynch & Co. $59.9 $516.3 Keryx Biopharmaceuticals Inc. (KERX) 9/29/04 7/15/05 5.78S $14.05 37.28 JP Morgan Securities $81.21 Bear, Stearns & Co. (co-lead) Jefferies & Co. Oppenheimer & Co. Brean Murray & Co. Punk, Ziegel & Co. $523.8 Momenta Pharmaceuticals Inc. (MNTA) 7/1/05 7/21/05 4.827S $27.02 30.35 Morgan Stanley & Co $130.4 $820.1 Deutsche Bank Securities (co-lead) Banc of America Securities SG Cowen & Co APRIL Progenics Pharmaceuticals Inc. (PGNX) MAY SeraCare Life Sciences Inc. (SRLS) JUNE JULY 44 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Follow-On Offerings (Continued) Company (Symbol) Date Filed Date Comm. Shares/ Units (M) Price Shares Out (M) Lead, Other Underwriters Gross (M) PostOffering Market Cap (M)@ Rigel Pharmaceuticals Inc. (RIGL) 7/1 1/05 7/15/05 4.198S $20.75 24.13 Credit Suisse First Boston $87.1 1 Lehman Brothers (co-lead) $500.7 Alexion Pharmaceuticals Inc. (ALXN) 5/14/04 8/12/05 2.5S $26.75 30.69 Morgan Stanley & Co. $66.88 $821.0 Amylin Pharmaceuticals Inc. (AMLN) 2/12/04 8/30/05 5.068S $31 Goldman, Sachs & Co. $157.1 $3,403.2 Anadys Pharmaceuticals Inc. (ANDS) 4/22/05 8/4/05 5.75S $12.40 32.31 Credit Suisse First Boston $71.3 SG Cowen & Co. (co-lead) Piper Jaffray & Co. Needham & Co. $400.6 Ariad Pharmaceuticals Inc. (ARIA) 12/19/03 8/5/05 8.625 $7.20 61.60 Lehman Brothers Lazard Capital Markets SG Cowen & Co. $62.1 $443.5 CuraGen Corp. (CRGN) 10/17/00 8/10/05 4S $5.50 55.17 Bear, Stearns & Co. $22 $303.4 Exelixis Inc. (EXEL) 10/27/04 8/17/05 6.5S $7.75 83.01 Goldman, Sachs & Co. $50.4 $643.3 Nastech Pharmaceutical Co. Inc. (NSTK) 9/30/04 8/25/05 1.725S $13.50 20.61 Needham & Co. SunTrust Robinson Humphrey Delafield Hambrecht $23.29 $278.2 ZymoGenetics Inc. (ZGEN) 6/17/05 8/4/05 $18 65.43 Merrill Lynch & Co. Pacific Growth Equities Bear, Stearns & Co. Piper Jaffray & Co. $135 $1,177.7 Acusphere Inc. (ACUS) 4/5/05 9/23/05 3.566S $5.25 21.40 Piper Jaffray & Co. $18.72 $1 12.4 BioDelivery Sciences International Inc. (BDSI) 8/3/05 9/30/05 4.4S $2 1 1.67 Ferris, Baker Watts Maxim Group GunnAllen Financial $8.8 $23.3 AUGUST 7.5S 109.78 SEPTEMBER BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 45 2005 Follow-On Offerings (Continued) Company (Symbol) Date Filed Date Comm. Shares/ Units (M) Price Geron Corp. (GERN) 5/5/04 9/16/05 6.9S $9 Meridian Bioscience Inc. (VIVO) 10/9/03 9/16/05 1.8S $17.50 Myogen Inc. (MYOG) 6/3/05 9/16/05 5.376S Progenics Pharmaceuticals Inc. (PGNX) 6/29/04 Renovis Inc. (RNVS) Shares Out (M) Lead, Other Underwriters Gross (M) PostOffering Market Cap (M)@ 64.81 UBS Investment Bank SG Cowen & Co. Needham & Co. Lazard Capital Markets Rodman & Renshaw WBB Securities $62.1 $583.3 25.92 Robert W. Baird & Co. $31.5 $453.6 $23.25 41.16 Goldman, Sachs & Co. CIBC World Markets First Albany Capital Lazard Capital Markets $125 $957.0 9/14/05 2.5S $23.90 24.15 UBS Investment Bank $59.75 CIBC World Markets (co-lead) $577.2 5/23/05 9/23/05 4S $13.50 28.86 Goldman, Sachs & Co. CIBC World Markets Piper Jaffray & Co. SG Cowen & Co. $389.6 CoTherix Inc. (CTRX) 9/20/05 10/6/05 $13 28.34 CIBC World Markets $56.4 UBS Investment Bank (co-lead) Piper Jaffray & Co. Needham & Co. $368.4 Dynavax Technologies Inc. (DVAX) 8/29/05 10/1 1/05 5.72S $6.25 30.47 Bear, Stearns & Co. CIBC World Markets Pacific Growth Equities $35.75 $190.4 GTx Inc. (GTXI) 8/17/05 10/1 1/05 6.325S $7.80 30.99 Lazard Capital Markets $49.34 SG Cowen & Co. (co-lead) $241.7 Idenix Pharmaceuticals Inc. (IDIX) 9/14/05 10/26/05 7.28S $20.61 $55.63 Morgan Stanley & Co. $150 Bear, Stearns & Co. (co-lead) $1,146.5 Panacos Pharmaceuticals Inc. (PANC) 7/7/05 10/6/05 $10.50 SG Cowen & Co. $86.63 Bear, Stearns & Co. (co-lead) Needham & Co. Leerink Swann & Co. $501.5 $54 OCTOBER 46 4.338S 8.25S 47.76 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Follow-On Offerings (Continued) Company (Symbol) Date Filed Date Comm. Shares/ Units (M) Price Threshold Pharmaceuticals Inc. (THLD) 9/27/05 10/12/05 6.25S $10.46 Digene Corp. (DIGE) 12/15/04 1 1/16/05 2.3S Durect Corp. (DRRX) 10/27/05 1 1/2/05 Myriad Genetics Inc. (MYGN) 4/20/05 1 1/3/05 Onyx Pharmaceuticals Inc. (ONXX) 1/31/05 Pharmaxis Ltd. (Australia; PXSL) Shares Out (M) Lead, Other Underwriters Gross (M) PostOffering Market Cap (M)@ 37.1 1 Morgan Stanley & Co. CIBC World Markets Lazard Capital Markets $65.38 $388.2 $28 22.44 JP Morgan Securities $64.4 Thomas Weisel Partners (co-lead) Goldman, Sachs & Co. SG Cowen & Co. $628.3 8.22S $5 60.68 Morgan Stanley & Co. $41.1 JP Morgan Securities (co-lead) CIBC World Markets Corp. WR Hambrecht + Co. $303.4 8.05S $18.50 39.00 JP Morgan Securities $148.9 Bear, Stearns & Co. (co-lead) UBS Securities (co-lead) Piper Jaffray & Co. First Albany Capital JMP Securities $721.5 1 1/18/05 5S $25.25 40.39 Morgan Stanley & Co. $126.3 Merrill Lynch & Co. (co-lead) $1,019.8 8/31/05 1 1/8/05 $1.61 174.4 CIBC World Markets JMP Securities $280.8 Point Therapeutics Inc. (POTP) 12/17/04 1 1/22/05 9.26S $3 32.75 Pacific Growth Equities $27.8 CIBC World Markets (co-lead) $98.3 Senomyx Inc. (SNMX) 10/24/05 1 1/4/05 $14.60 29.66 Deutsche Bank Securities $59 $433.0 Digene Corp. (DIGE) 12/15/04 12/15/05 0.3S $28 22.44 JP Morgan Securities $8.4 Thomas Weisel Partners (co-lead) Goldman, Sachs & Co. SG Cowen & Co. $628.3 Point Therapeutics Inc. (POTP) 12/17/04 12/2/05 1.21S $3 32.75 Pacific Growth Equities $3.6 CIBC World Markets (co-lead) $98.3 NOVEMBER 19.5S 4.05S BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 $31.4 47 2005 Follow-On Offerings (Continued) Company (Symbol) Date Filed Date Comm. Shares/ Units (M) Price Shares Out (M) Lead, Other Underwriters Gross (M) PostOffering Market Cap (M)@ Biopure Corp. (BPUR) 12/1/05 12/21/05 10.12S $0.68 34.48 Dawson James Securities $6.9 Noble International (co-lead) $23.5 Dendreon Corp. (DNDN) 10/26/05 12/7/05 1 1.5S $4.50 70.86 Banc of America Securities $51.8 JMP Securities Lazard Capital Markets $318.9 Medivation Inc. (OTC BB: MDVN) 10/6/05 12/15/05 5.635S $2 24.76 Adams Harkness $1 1.27 $49.5 OxiGene Inc. (OXGN) 12/1/05 12/15/05 7.475S $3.65 28.04 SG Cowen & Co. $27.3 Lazard Capital Markets (co-lead) $102.3 ViroPharma Inc. (VPHM) 10/19/01 12/7/05 10.35S $16.75 68.26 Goldman, Sachs & Co. $173.4 Piper Jaffray & Co. (co-lead) SG Cowen & Co. Lazard Capital Markets $1,143.6 DECEMBER Notes: Totals include shares sold to satisfy overallotment options, in full or in part, where applicable. @ Market capitalization calculated is based on the offering price. Foreign currency is converted to U.S. dollars based on the exchange rate at the time of the offering. Unless otherwise noted, trading symbols are listed on the Nasdaq market. OTC BB = Over-the-Counter Bulletin Board. 48 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 After-Market Performance: Class of 2005 U.S. Initial Public Offerings Company Offering Month Offering Price 2005 Close % Change Accentia Biopharmaceuticals Inc. October $8 $5.05 -37% Advanced Life Sciences Holdings Inc. August $5 $3.92 -22% Aspreva Pharmaceuticals Corp. March $1 1 $15.72 +43% Avalon Pharmaceuticals Inc. September $10.50 $4.50 -57% CardioVascular BioTherapeutics Inc. March $10 $4.55 -55% Coley Pharmaceutical Group Inc. August $16 $15.16 -5% Combinatorx Inc. November $7 $8.18 +17% Favrille Inc. February $7 $4.06 -42% Genomic Health Inc. September $12 $9.1 1 -24% Gentium SpA (Italy) June $9 $7.75 -14% Icagen Inc. February $8 $6.45 -19% Somaxon Pharmaceuticals Inc. December $1 1 $9.95 -10% Sunesis Pharmaceuticals Inc. September $7 $4.98 -29% Threshold Pharmaceuticals Inc. February $7 $14.45 +106% ViaCell Inc. January $7 $5.62 -20% XenoPort Inc. June $10.50 $17.95 +71% Average Change: -6.1% BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 49 After-Market Performance: Follow-On Class of 2005 U.S. Public Follow-On Stock Offerings Company Offering Month Offering Price Acusphere Inc. September $5.25 $5.34 -1% Alexion Pharmaceuticals Inc. August $26.75 $20.25 -24% Amylin Pharmaceuticals Inc. August $31 $39.92 +29% Amylin Pharmaceuticals Inc. January $22 $39.92 -81% Anadys Pharmaceuticals Inc. August $12.40 $8.80 -29% Arena Pharmaceuticals Inc. February $6 $14.21 +137% Ariad Pharmaceuticals Inc. August $7.20 $5.85 -19% Barrier Therapeutics Inc. February $19.50 $8.20 -58% BioDelivery Sciences International Inc. September $2 $2.48 +24% Bioenvision Inc. February $8 $6.53 -18% BioMarin Pharmaceutical Inc. July $7.05 $10.78 -53% Biopure Corp. December $0.68 $0.78 -15% Cardiome Pharma Corp. March $6 $10.10 -68% CoTherix Inc. October $13 $10.58 -19% CoTherix Inc. February $8.90 $10.58 -19% CuraGen Corp. August $5.50 $3.08 -44% CV Therapeutics Inc. June $21.60 $24.73 -14% Dendreon Corp. December $4.50 $5.42 -20% Digene Corp. November $28 $29.17 -4% Durect Corp. November $5 $5.07 -1% Dynavax Technologies Inc. October $6.25 $4.21 -33% Exelixis Inc. August $7.75 $9.42 +35% Geron Corp. September $9 $8.61 -4% 50 2005 Close % Change BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 After-Market Performance, Follow-On Offerings (Continued) Company Offering Month Offering Price GTx Inc. October $7.80 $7.56 -3% Idenix Pharmaceuticals Inc. October $20.61 $17.1 1 -17% ISTA Pharmaceuticals Inc. January $8.88 $6.36 -28% Keryx Biopharmaceuticals Inc. July $14.05 $14.64 +4% La Jolla Pharmaceutical Co. January $7 $3.70 -47% Martek Biosciences Corp. January $49.10 $24.60 -50% Meridian Bioscience Inc. September $17.50 $20.14 +15% Momenta Pharmaceuticals Inc. July $27.02 $22.04 -18% Myogen Inc. September $23.25 $30.10 +29% Myriad Genetics Inc. November $18.50 $20.80 +12% Nastech Pharmaceutical Co. August $13.50 $14.72 +9% Neose Technologies Inc. February $4 $1.94 -52% Neurochem Inc. March $15.30 $14.22 -7% Northfield Laboratories Inc. February $15 $13.40 -1 1% Nuvelo Inc. February $7.50 $8.1 1 +8% Onyx Pharmaceuticals Inc. November $25.25 $28.80 +14% OxiGene Inc. December $3.65 $3.97 +9% Panacos Pharmaceuticals Inc. October $10.50 $6.93 -34% Point Therapeutics Inc. November $3 $3.45 +15% Progenics Pharmaceuticals Inc. September $23.90 $25.01 +5% Progenics Pharmaceuticals Inc. June $19.25 $25.01 +30% Progenics Pharmaceuticals Inc. April $15.25 $25.01 +64% Renovis Inc. September $13.50 $15.30 +13% Rigel Pharmaceuticals Inc. July $20.75 $8.36 -60% Senomyx Inc. November $14.60 $12.12 -20% SeraCare Life Sciences Inc. May $12.25 $8.87 -28% BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Close % Change 51 2005 After-Market Performance, Follow-On Offerings (Continued) Company Offering Month Offering Price Telik Inc. January $18.75 $16.99 -9% Threshold Pharmaceuticals Inc. October $10.46 $14.45 -38% Tercica Inc. February $8 $7.17 -10% Vertex Pharmaceuticals Inc. June $13 $27.67 +1 13% ViroPharma Inc. December $16.75 $18.50 +10% Vivus Inc. March $3.40 $2.96 -13% Zonagen Inc. January $4 $5.1 1 +28% ZymoGenetics Inc. August $18 $17.01 -6% Average Change: 52 2005 Close % Change +4.5% BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Initial Public Offerings Gross Proceeds ($M) 450 33 IPOs; $1,503M Total Gross Proceeds 364 375 300 234 225 149 150 142 109 74 89 41 75 131 72 91 7 0 Jan. (2) Feb. (6) March (3) April (1) May (2) June (5) July (1) Aug. (2) Sept. (3) Oct. (3) Nov. (3) Dec. (2) Month (Number of IPOs) 2004 Initial Public Offerings 37 IPOs; $2,045M Total Gross Proceeds Gross Proceeds ($M) 450 400 375 390 292 300 284 215 225 157 150 143 112 75 34 0 0 27 0 Jan. (1) Feb. (4) March (5) April (6) May (3) June (7) July (6) Aug. (1) Sept. (0) Oct. (2) Nov. (0) Dec. (2) Month (Number of IPOs) 2003 Initial Public Offerings 1 1 IPOs; $563M Total Gross Proceeds Gross Proceeds ($M) 420 350 318 280 210 150 140 63 70 0 0 Jan (0) 0 Feb. (0) 0 0 March (0) April (0) 0 0 May (0) June (0) 0 July (0) 32 0 Aug. (0) Sept. (1) Oct. (6) Nov. (2) Dec. (2) Month (Number of IPOs) 2002 Initial Public Offerings Gross Proceeds ($M) 375 4 IPOs; $456M Total Gross Proceeds 325 300 225 150 120 75 0 0 0 Jan (0) Feb. (1) March (0) April (2) 0 11 May (0) June (1) 0 July (0) 0 0 0 0 0 Aug. (0) Sept. (0) Oct. (0) Nov. (0) Dec. (0) Month (Number of IPOs) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 53 2005 Follow-On Offerings 65 Follow-On Offerings; $4,091M Total Gross Proceeds Gross Proceeds ($M) 750 625 588 533 500 511 427 444 386 360 375 141 250 125 271 230 31 43 0 Jan. (6) Feb. (8) March (3) April (1) May (1) June (3) July (4) Aug. (8) Sept. (7) Oct. (6) Nov. (9) Dec. (5) Month (Number of Follow-ons) 2004 Follow-On Offerings 705 750 Gross Proceeds ($M) 45 Follow-On Offerings; $3,405M Total Gross Proceeds 696 591 625 500 326 375 250 241 216 179 157 136 125 71 88 Sept. (1) Oct. (2) 0 Jan. (3 Feb. (12) March (3) April (3) May (4) June (2) July (7) Aug. (0) Nov. (4) Dec. (4) Month (Number of Follow-ons) 2003 Follow-On Offerings 693 700 Gross Proceeds ($M) 600 42 Follow-On Offerings; $3,133M Total Gross Proceeds 462 500 400 300 342 337 305 255 170 200 88 75 100 210 162 34 0 Jan. (3) Feb. (1) March (3) April (1) May (2) June (3) July (4) Aug. (4) Sept. (6) Oct. (5) Nov. (6) Dec. (4) Month (Number of Follow-ons) 2002 Follow-On Offerings 300 20 Follow-On Offerings; $925M Total Gross Proceeds 226 Gross Proceeds ($M) 250 199 200 157 137 150 100 66 59 50 59 22 0 0 Jan. (2) Feb. (4) March (4) April (0) 0 May (2) June (3) July (0) 0 0 Aug. (0) Sept. (2) Oct. (2) Nov. (1) Dec. (0) Month (Number of Follow-ons) 54 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Quarter:Year Gross Proceeds Of Biotech Public Stock Offerings, First Through Fourth Quarter 1995-2005, Initial And Follow-On Offerings Combined 1,476 1,587 4Q:05 3Q:05 2Q:05 1Q:05 4Q:04 3Q:04 2Q:04 1Q:04 4Q:03 3Q:03 2Q:03 1Q:03 4Q:02 3Q:02 2Q:02 1Q:02 4Q:01 3Q:01 2Q:01 1Q:01 4Q:00 3Q:00 2Q:00 1Q:00 4Q:99 3Q:99 2Q:99 1Q:99 4Q:98 3Q:98 2Q:98 1Q:98 4Q:97 3Q:97 2Q:97 1Q:97 4Q:96 3Q:96 2Q:96 1Q:96 4Q:95 3Q:95 2Q:95 1Q:95 840 1,685 1,281 98 1,207 1,937 1,544 1,364 274 506 196 199 417 569 213 1,533 866 1,191 2,386 7,992 4,020 2,394 340 396 8,907 3,936 93 193 320 419 186 784 520 867 735 498 804 113 73 0 1,000 1,264 1,981 1,179 2,000 3,000 4,000 5,000 6,000 7,000 8,000 9,000 10,000 Gross Proceeds ($M) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 55 2005 Miscellaneous Financings Of Public Biotech Companies Company (Symbol)# Type Of Financing Number Of Shares, Units Or Warrants (M) Amount Raised ($M) Investors; Placement Agents; Details (Date) Private placement of stock 4.8S $12 The private placement concludes an October 2002 deal between Aastrom and Fusion Capital Fund II LLC, which also purchased $12M of stock in the first tranche (1/13) Alexion Private Pharmaceuticals placement of Inc. (ALXN) convertible notes N/A $150 The 1.375% convertible senior notes due 2012 are convertible into stock at $31.46 per share; the total includes the purchase of $25M in notes per the investors’ option (1/18) Alteon Inc. (AMEX:ALT) Private placement of stock 9.5S $10 The shares were sold from a shelf registration at $1.05 each; Rodman & Renshaw LLC was placement agent (1/7) Antigenics Inc. (AGEN) Private placement of convertible notes N/A $50 The 5.25% convertible senior notes initially are convertible into common stock at $10.76 per share; investors have an option on another $10M in notes (1/20) ArQule Inc. (ARQL) Private placement of stock 5.78S $30.35 ArQule sold the shares from a shelf registration at $5.25 each in a direct offering; JP Morgan Securities Inc. was placement (1/25) AtheroGenics Inc. (AGIX) Private placement of convertible notes N/A $200 The 1.5% notes due 20 1 2 are convertible into common shares at an initial price of about $25.92 per share; the total includes $25M in notes purchased under an overallotment option (1/7) AVI BioPharma Inc. (AVII) Private placement of stock and warrants 8S and 1.6W $24 AVI sold the shares from a shelf registration at $3 each; the four-year warrants are exercisable at $5 per share; Rodman & Renshaw LLC was placement agent (1/19) Biofusion plc (UK; AIM:BFN) Private placement of stock 5.49S £8.2 ($15.45) Biofusion gained a listing on the Alternative Invesment Market concurrent with the placement, giving the company a market cap of about £28.2M; Code Securities Ltd. was adviser and broker for the deal (1/28) Biopure Corp. (BPUR) Private placement of stock 22.2S $1 1.3 The shares were sold from a shelf registration at $0.51 each to individual and institutional investors; C.E. Unterberg, Towbin LLC was placement agent (1/5) JANUARY Aastrom Biosciences Inc. (ASTM) 56 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Number Amount Of Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) 0.048U $12 The company sold 480 units at $25,000 per unit; each unit consists of one share of Series A stock, each convertible into 10,000 common shares, and one three-year warrant that entitles the holder to purchase 5,000 shares; Brookshire Securities Corp. was placement agent (1/31) ChemGenex Private Pharmaceuticals placement of Ltd. (Australia; stock ASX:CXS) 14.9S A$8.2 ($6.3) The shares were sold at A$0.55 each; investors included Charter Pacific Corp. Ltd., which maintained its 20. 1% stake, Queensland Investment Corp., Merck Sante, HSBC and Acorn Capital (1/24) Chromos Molecular Systems Inc. (Canada; TSE:CHR) Private placement of stock and warrants 2.215S and 1.108W C$1.06 ($0.86) Units were sold for C$0.48 apiece; each consists of one share and a half a warrant; each whole warrant allows for the purchase of one share at C$0.60 for two years (1/14) ConjuChem Inc. (Canada; TSE:CJC) Bought-deal financing 4.625S C$21.74M ($17.53) Orion Securities Inc. and GMP Securities Ltd. co-led the financing, in which shares were sold at $4.70 each; underwriters have an option to purchase up to 694,000 additional shares (1/28) CytRx Corp. (CYTR) Private placement of stock and warrants 17.33S and 8.67W $21.3 The shares were sold for about $1.23 each to institutional investors; warrants are exercisable for $2 per share; Rodman & Renshaw LLC was placement agent (1/21) Depomed Inc. Private placement of stock 5.036S $22.66 The shares are being sold from a shelf registration at $4.50 each; Thomas Weisel Partners LLC was placement agent (1/7) DOV Pharmaceutical Inc. (DOVP) Private placement of convertible notes N/A $15 Purchasers of $65M of convertible subordinated debentures due 2025 exercised their option on another $15M in notes; they have an interest rate of 2.5% and an initial conversion price of $22.75 per share (1/4) Genetronics Private Biomedical placement of Corp. (AMEX:GEB) stock and warrants ND $3.03 Shares were sold at $4.05 each to institutional investors; 80% of the funds are being held until Sept. 30, unless triggered by a milestone earlier; twoyear warrants representing 33% of the total are exercisable at $5.50 per share (1/12) Geron Corp. (GERN) 2S $12.5 Investors in a November 2004 private placement exercised warrants to purchase 2M shares (1/12) 7.7S $10.4 The shares were sold from a shelf registration at $1.35 each; SG Cowen & Co. LLC was placement agent (1/24) CepTor Corp. (OTC BB:CEPO) Type Of Financing Private placement of units Warrants exercise GTC Private Biotherapeutics placement of Inc. (GTCB) stock BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 57 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Lorus Therapeutics Inc. (Canada; TSE:LOR) Private placement of convertible notes N/A $5 TEMIC made the second of three planned $5M investments; it has an option to convert the debenture into common stock at $1 per share (1/17) Ortec International Inc. (OTC BB: ORTN) Private placement of stock and warrants N/A $6.4 The total includes a $5M private placement and a $1.4M equity transaction; at the same time, Series C preferred shareholders converted the shares into common stock on the same terms; together, about 15.8M shares and five-year warrants to purchase 7.9M warrants were issued (1/6) Pharming Group NV (the Netherlands; Euronext:PHARM) Exercise of warrants and options ND €7 ($9.1) Investors in a February 2004 financing exercised warrants to purchase 3.3M shares at €2 each; also, company insiders exercised 0.5M options and warrants (1/24) Pluristem Life Systems Inc. (Israel; OTC BB:PLRS) Private placement of securities ND $0.76 Terms of the interim private placement were not disclosed (1/27) RegeneRx BioPrivate pharmaceuticals placement of Inc. (OTC BB:RGRX) stock and warrants 1.8S and 0.45W $5.86 Investors led by Sigma-Tau Group bought the shares at $3.25 each; the three-year warrants are exercisable at $4.06 per share; ThinkEquity Partners LLC was placement agent for the twotranche deal (1/3) Sinovac Private Biotech Ltd. placement of (China; AMEX:SVA) units 0.492S and 0.492W $1.48 Institutional investors paid $3 per unit, which consisted of one share and a one-year warrant exercisable at $3.35 per share (1/3) Sirna Therapeutics Inc. (RNAI) Warrants exercise 2.7S $6.8 Investors exercised warrants for 2.7M shares at about $2.52 each; investors were Sprout Group, Venrock Associates, Oxford Bioscience Partners and Granite Global Ventures; they were issued 1.1M new five-year warrants exercisable at $3.85 per share (1/4) Targeted Genetics Corp. (TGEN) Private placement of stock 3.947S $6 Celladon Corp. investors Enterprise Partners and Venrock Associates purchased the stock in a directed public offering at $1.52 per share following a collaboration between Celladon and Targeted Genetics (1/4) Tripos Inc. (TRPS) Private placement of various securities N/A $4 Horizon Technology Finance LLC and Sand Hill Capital invested in the deal that included $3.5M of subordinated debt, 1 1 1,606 shares of stock and warrants to purchase 156,250 shares (1/5) 58 Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Vasogen Inc. (Canada; VSGN) Private placement of stock 9S $42.3 Vasogen sold the shares from a shelf registration at $4.70 per share; SG Cowen & Co. LLC was lead agent and sole book manager for the deal; Needham & Co. Inc. was co-lead agent, and A.G. Edwards & Sons Inc. was placement agent (1/28) Vion Private Pharmaceuticals placement of Inc. (VION) stock 10S $32.5 Vion sold the shares from a shelf registration at $3.25 each to institutional investors; CIBC World Markets Corp. and Leerink Swann & Co. were placement agents (1/26) FEBRUARY Acusphere Inc. (ACUS) Sale of convertible stock N/A $45 Acusphere sold 900,000 shares of 6.5% convertible exchangeable preferred stock at $50 per share; it is convertible into common stock at $6.86 per share; underwriters Piper Jaffray & Co. (lead), SG Cowen & Co. and C.E. Unterberg, Towbin have an overallotment option on another 100,000 shares (2/18) Alkermes Inc. (ALKS) Private placement of notes N/A $170 The 7% notes due 2018 will be paid solely from manufacturing and royalty revenues from sales of Risperdal Consta, a schizophrenia drug marketed by J& J unit Janssen-Cilag (2/3) BioBalance Corp. (subsidiary of New York Health Care Inc.; OTC BB:BBAL) Private placement of stock and warrants 7.9S and 3.9W $4.9 The shares were sold at $0.62 each; warrants are exercisable at $0.78 per share; investors included Mellon HBV Alternative Strategies and Little Gem Life Sciences Fund LLC; placement agent Sterling Financial Investment Group got warrants to purchase shares equal to 15% of the offering at $0.62 per share (2/24) BioCryst Private Pharmaceuticals placement of Inc. (BCRX) stock 4.35S $23.9 The shares were sold from a shelf registration at $5.50 each; Leerink Swann & Co. was placement agent (2/17) BioDelivery Sciences International Inc. (BDSI) Convertible debt deal N/A $2.5 Laurus Master Fund Ltd. bought the three-year, prime-plus-2% note convertible into common stock at $3.10 per share; Laurus also got warrants to purchase up to 350,000 shares at $3.88 per share (2/23) Cytomedix Inc. (OTC BB: CYME) Warrants and options exercise ND $1.4 Investors exercised about 1. 1M warrants and options between Oct. 1, 2004, and Feb. 15, 2005 (2/15) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 59 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Discovery Laboratories Inc. (DSCO) Private placement of stock 5.05S $29.1 Shares in the registered direct offering were sold at $5.76 each; SG Cowen & Co. LLC was placement agent (2/18) DOR BioPharma Inc. (AMEX:DOR) Private placement of stock and warrants 8.4S and 6.3W $3.77 Institutional investors purchased the stock and warrants; the five-year warrants are exercisable at 101% of the closing price the day of the deal, starting 180 days after the deal’s close (2/3) Ecopia BioSciences Inc. (Canada; TSE:EIA) Bought-deal financing 1 1U C$9.9 ($8) Units, sold at C$0.90 each, consist of one share and one-third of a warrant; each two-year whole warrant allows for the purchase of one share at C$1.03; the underwriting syndicate was led by Desjardins Securities Inc. and included First Associates Investments Inc. and Orion Securities Inc.; the totals include their purchase of 1M units per their overallotment option (2/25) GeneMax Corp. (Canada; OTC BB: GMXX) Private placement of stock and warrants 9.3S and 4.65W $1.4 The warrants are exercisable from $0.15 to $0.50 each, depending on the timing and other factors; finders’ fees of 8% cash and 5% warrants were paid to certain brokers in the deal (2/15) GW Private Pharmaceuticals placement of plc (UK; LSE:GWP) stock and warrants 2.03S and 0.203W £2.5 ($4.8) GW’s U.S. founding investor increased its stake in the company with the purchase of shares at £1.235 per share; the five-year warrants are exercisable at £1.35 per share (2/28) MultiCell Technologies Inc. (OTC BB: MUCL) Private placement of stock and warrants 26.67S and 26W $4 The shares were sold at $0.15 each; 18M of the three-year warrants are exercisable at $0.20 and 8M of them at $0.30; Mercator Group Advisors LLC and Marr Group were the lead investors (2/14) Neurologix Inc. (OTC BB: NRGX) Private placement of stock and warrants 1.896S and 0.474W $2.46 The shares were sold at $1.30 each; the five-year warrants are exercisable at $1.625 per share; Merlin Biomed Group led the financing, which was done in two closings (2/1 1 and 2/25) Oncolytics Biotech Inc. (Canada; ONCY) Warrants exercise 0.814S $3.25 Investors in a June 2003 financing exercised warrants for about 0.814M shares (2/22) PharmaFrontiers Corp. (OTC BB:PFTR) Private placement of convertible notes N/A $6.1 The $6.1M convertible notes will be automatically exchanged for stock if PharmaFrontiers raises $10M in a stock sale before the notes’ maturity on Nov. 30, 2005 (2/14) 60 Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Protein Design Labs Inc. (PDLI) Private placement of convertible notes N/A $250 The 2% notes due 2012 are convertible into common stock at $23.69 per share; investors have an option to purchase another $50M of the notes (2/9) Scolr Pharma Inc. (AMEX:DDD) Private placement of stock 3.75S $15 The shares were sold at $4 each; the placement agent, Taglich Brothers, received a fee and fiveyear warrants to purchase up to 75,000 shares (2/8) Tm Bioscience Corp. (Canada; TSE:TMC) Bought-deal financing 4.33S C$9.3 ($7.6) The shares were sold at C$2.15 through a syndicate of underwriters led by Orion Securities Inc. and including Dlouhy Merchant Group (2/3) Vernalis plc (UK; VNLS) Private placement and open offer 43.3S £30.3 ($57.9) The shares were sold at 70 pence each; existing shareholders were offered five new shares for every 18 ordinary shares held (2/24) XOMA Ltd. (XOMA) Private placement of convertible notes N/A $60 The 6.5% senior notes are convertible into common stock at an initial price of $1.87; purchasers have an option to buy up to $5M more of the notes (2/1) ALDA Pharmaceuticals Corp. (Canada; CDNX:APH) Private placement of stock and warrants 2.205S and 2.205W C$0.22 ($0.18) Units were sold at C$0.10 each; the 18-month warrants are exercisable at C$0.20 per share; placement agent Canaccord Capital Corp. was paid a 10% fee and received 220,500 warrants (3/16) Allos Therapeutics Inc. (ALLP) Private placement of convertible stock N/A $52 Allos sold the exchangeable preferred stock from a shelf registration to Warburg Pincus Private Equity VIII LP at a 7% discount to a 20-day average; the stock will accrue dividends of 10% if it remains outstanding after 15 months; the total includes a $2M follow-on investment; Needham & Co. Inc. was placement agent (3/3) Altachem Pharma Ltd. (Canada; CDNX:AAF) Private placement of convertible notes N/A C$1 ($0.82) AltaChem issued 8% notes with a one-year maturity that are convertible into common shares at C$0.45 per share (3/23) Altachem Pharma Ltd. (Canada; CDNX:AAF) Private placement of stock and warrants 1.772S and 0.861W C$0.44 ($0.36) AltaChem closed the first tranche of the non-brokered placement; the shares sold at C$0.25 each, and the one-year warrants are exercisable at $0.45 per share (3/7) MARCH BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 61 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) Amazon Biotech Inc. (OTC BB:AMZB) Private placement of stock and warrants 0.7S and 1.1W $0.35 Amazon closed two deals in which it sold units at $0.50 each; warrants are exercisable at $0.58, $0.72 and $1.13 per share; Parker Financial Corp. got a finder's fee of $25,000 and a warrant to purchase 125,000 shares at $1.13 per share (3/14) BioMS Medical Corp. (Canada; TSE:MS) Private placement of stock and warrants 1 1.5S and 1 1.5W C$41.4 ($34) Units consisting of one share and a four-year warrant exercisable at C$5 were sold at C$3.60 each; the underwriting syndicate was led by Fraser Mackenzie Ltd. and included Pacific International Securities Inc. and Dlouhy Merchant Group Inc. (3/23) Boston Life Sciences Inc. (BLSI) Private placement of stock 2S $5 Shares in the deal were sold at $2.50 each (3/9) BrainStorm Cell Private Therapeutics placement of (Israel; OTC BB: securities BCLI) ND $1.5 The company said it completed the final closing in a $1.5M seed private placement; details were not disclosed (3/1) Callisto Private Pharmaceuticals placement of Inc. (AMEX:KAL) stock 1.99S $3.02 The shares were sold at $1.52 each in a financing led by current institutional shareholders and including certain members of the company’s management (3/10) Connetics Corp. (CNCT) Private placement of convertible notes N/A $200 The 2% notes due in March 2015 are convertible into cash and, under certain circumstances, shares of stock at an initial price of $35.46 per share; the total includes $50M in notes purchased per the lead investor’s option (3/17) Cytos Biotechnology AG (Switzerland; SWX:CYTN) Private placement of stock 0.46S CHF21.4 ($18.5) Swissfirst Bank AG purchased the shares, and placed them with institutional investors (3/1 1) Encysive Private Pharmaceuticals placement of Inc. (ENCY) convertible notes N/A $130 The 2.5% notes due 2012 initially are convertible into common stock at about $13.95 per share; the total includes the purchase of $15M in notes per an investor option (3/1 1) Evolutec Group plc (UK; AIM:EVC) 7.143S £9.5 ($17.9) The shares were placed at 140 pence each in a deal fully underwritten by Collins Stewart; the shares were placed at a discount of 21.6% (3/23) 62 Private placement of stock Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) Evotec OAI AG (Germany; FSE:EVT) Private placement of stock 10S €27.2 ($36.6) Investors committed to purchase 10M share at €2.72 at the same time that Evotec disclosed its all-stock reacquisition of Evotec Neurosciences (3/7) GlycoGenesys Inc. (GLGS) Private sale of convertible stock and warrants 2S and 2W $2 The company sold 2,000 shares of convertible, redeemable Series D preferred stock, currently convertible into 2M shares of common stock, and warrants to purchase 2M shares at $1.23 each; a second closing of $4.5M already has been agreed upon (3/4) Helix BioMedix Inc. (OTC BB:HXBM) Private placement of stock and warrants 1.665S and 0.125W $2.5 Helix completed a two-part private financing that brought in a total of $2.5M; the five-year warrants are exercisable at $1.50 per share (3/2) Hemosol Corp. (Canada; HMSL) Private placement of convertible stock, stock and warrants N/A and 10.95S and 10.95W C$13.4 ($1 1.1) Laurus Master Fund Ltd. purchased a three-year, 2%, $5M note convertible into stock at $0.69 per share; it also got a five-year warrant for the purchase of 2.73M shares at $0.86 and $1.04 per share; separately, Hemosol sold 10.95M special warrants at C$0.67 each; each consists of one share and a five-year warrant to purchase one share at C$1; Life Science Group Inc. and Loewen, Ondaatje, McCutcheon Ltd. were placement agents (3/31) Insmed Inc. (INSM) Private placement of convertible notes and warrants N/A and 14.9W $35 The five-year, 5.5% notes are convertible into stock at $1.295 per share; the deal also included five-year warrants exercisable for 14.9M shares at an initial price of $1.36 per share; Wells Fargo Securities was lead placement agent; C.E. Unterberg, Towbin and Trout Capital LLC were co-agents (3/15) Life Medical Sciences Inc. (OTC BB:CHAI) Warrants exercise 6.6S $0.8 The warrants, issued in a private placement in Europe in March 2003, were exercised at $0.12 each (3/31) Medical Private Discoveries Inc. placement of (OTC BB:MLSC) securities ND $3 M.A.G. Capital LLC provided MDI with $3M for the acquisition of the German firm Savetherapeutics AG; financing terms were not disclosed (3/16) MorphoSys AG (Germany; FSE:MOR) 0.49S €17.4 ($23.1) Shares were sold at €35.50 each; WestLB AG was the sole manager for the deal (3/16) Private placement of stock BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Investors; Placement Agents; Details (Date) 63 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) NeoRx Corp. (NERX) Private placement of stock and warrants 3.32S and 1.328W $4.1 The shares were sold at $1.25 each, and the fiveyear warrants are exercisable at $2 per share; Rodman & Renshaw LLC was placement agent (3/4) Neurologix Inc. (OTC BB: NRGX) Private placement of stock and warrants 0.539S and 0.135W $0.7 The shares were sold at $1.30 each and the fiveyear warrants are exercisable at $1.625 per share; it was a follow-on deal to $2.46M in financings in January under the same terms (3/4) OxiGene Inc. (OXGN) Private placement of stock 3.336S $15 The shares were sold from a shelf registration to institutional investors at $4.50 each; Legg Mason Wood Walker Inc. was lead placement, with Lazard Freres & Co. LLC co-placement agent (3/4) Plethora Solutions Holdings plc (UK; AIM:PLE) Stock sale 7.4S £10 ($18.7) The company, formerly named MedPharma plc, raised £10 as it gained a listing on the Alternative Investment Market, selling shares at 135 pence each and giving it a £30M market cap (3/24) Pluristem Life Systems Inc. (Israel; OTC BB:PLRS) Private placement of stock and warrants ND $2.44 Pluristem completed a $3.2M interim financing; $0.76M of the total was disclosed in January; details on the financing were not disclosed (3/7) Point Therapeutics Inc. (POTP) Private placement of stock 3.65S $16.43 The shares were sold from a shelf registration at $4.50 each in a direct offering; SG Cowen & Co. LLC was lead agent and RBC Capital Markets was coagent for the offering (3/1) Proximagen Neurosciences plc (UK; AIM:PRX) Private placement of stock 9.12S £13.5 ($25.4) Proximagen gained a listing on the AIM with the financing, and has a market capitalization of £29.7; KBC Peel Hunt Ltd. was adviser and broker in the deal (3/31) Sinovac Warrants Biotech Ltd. exercise (China; AMEX:SVA) ND $3.4 Investors in a February 2004 financing exercised warrants at $1.70 per share; the company extended the exercise period until April 30 (3/1) VaxGen Inc. (Pink Sheets: VXGN) Private placement of convertible notes N/A $31.5 The 5.5% notes due 2010 initially are convertible into stock at $14.76 per share (3/31) V.I. Technologies Inc. (VITX) Private placement of stock and warrants 100S and 45W $20 The deal was made concurrent with the closing of the merger with Panacos Pharmaceuticals Inc.; the five-year warrants are exercisable at $0.24 per share; SG Cowen & Co. LLC was lead placement agent and Legg Mason Wood Walker was co-agent (2/1 1) 64 Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Viventia Biotech Inc. (Canada; TSE:VBI) Bridge loans N/A C$2 ($1.64) Viventia Chairman Leslie Dan provided loans of C$0.5M and C$1.5M that carry a 4.5% annual interest rate; the board also authorized an additional bridge loan of C$42.6M from Dan (3/23) Acadia Private Pharmaceuticals placement of Inc. (ACAD) stock and warrants 5.3S and 1.3W $36 New and existing institutional investors are purchasing shares at about $6.82 each; the warrants are exercisable at $8.148 per share (4/15) Access Private Pharmaceuticals placement of Inc. (AMEX:AKC) convertible notes N/A $2.6 The debentures are convertible into common stock at $4 per share; separately, Cornell Capital committed to provide up to $15M that Access can draw down through stock sales for two years (4/4) Advancis Pharmaceutical Corp. (AVNC) 6.8S and 2.4W $27.25 The shares were priced at $3.98 each; the five-year warrants are exercisable at $4.78 per share; the financing syndicate included Omega Fund, HealthCare Ventures and Rho Ventures, which together purchased 5.8M shares (4/26) Avanir Private Pharmaceuticals placement of Inc. (AMEX:AVN) stock 7.77S $17.1 Avanir sold the Class A shares from a shelf registration at $2.20 each; CIBC World Markets Corp. was placement agent and Leerink Swann & Co. was co-placement agent (4/6) AVAX Private Technologies placement of Inc. (OTC BB:AVXT) stock and warrants 25.24S and 7.57W $8.58 The shares were sold at $0.34 each; half the warrants are convertible into stock at $0.41 per share and half at $0.48; investors included Credit Suisse Equity Global Biotech Fund, BSI – New Biomedical Frontier Fund and JFE Hottinger & Co.; Privateq Advisors acted as an adviser in the deal (4/6) Biotech Holdings Ltd. (Canada; OTC BB: BIOHF) Private placement of stock and warrants 2.02S and 2.02W $0.5 Pierpoint Investissements SA is purchasing 1.01M shares at $0.2475 each, and another 1.01M shares from the company’s president, who in turn will invest that $0.25M in the company; the warrants are exercisable at $0.33 per share (4/12) Emisphere Technologies Inc. (EMIS) Private placement of stock and warrants 4S and 1.5W $15.74 Emisphere sold the shares from a shelf registration; the warrants are exercisable at $4 per share; Harris Nesbitt Corp. was placement agent (4/1) N/A $4.5 Xmark Funds and affiliates are providing the twoyear, 5% loan; they also got warrants to purchase 2M shares of Genaissance stock at $2.25 per share (4/22) APRIL Private placement of stock and warrrants Genaissance Private loan Pharmaceuticals and warrants Inc. (GNSC) placement BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 65 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Geron Corp. (GERN) Private placement of stock and warrants 0.741S and 0.37W $4 Geron sold the shares from a shelf registration at $5.40 each, along with warrants to purchase 370,000 shares at a premium; the deal was made with investors from Hong Kong (4/25) Hana Biosciences Inc. (OTC BB: HNAB) Private placement of stock and warrants 3.78S and 1.13W $4.83 Investors included Pogue Capital Management, Xmark Capital Partners, Mosiax Ventures, Atlas Equity, Coqui Capital and Emerging Technology Partners; Griffin Securities Inc. was lead placement agent (4/26) Immunomedics Inc. (IMMU) Private placement of convertible notes and warrants N/A and ND $37.68 The 5% convertible notes due 2008 initially are convertible into common stock at $2.62 per share; the three-year warrants are exercisable at $2.98 per share; investors have a 120-day option to buy up to 20% more of the notes and warrants; Lazard Freres & Co. LLC was lead placement agent; C.E. Unterberg, Towbin was co-placement agent (4/27) Lorus Therapeutics Inc. (Canada; TSE:LOR) Private placement of convertible notes N/A C$5 ($4) TEMIC made a C$5M investment in the third and final tranche of a C$15M deal; the notes are convertible into common stock at C$1 per share (4/18) Mologen AG (Germany; FSE: MGNG) Private placement of stock 0.6S €2.19 ($2.8) The shares were sold at €3.65 each to institutional investors from German-speaking countries (4/22) Nabi BioPrivate pharmaceuticals placement of (NABI) convertible notes N/A $100 The 2.875% senior notes due 2025 are convertible into common stock at $14.32 per share, a 30% premium; purchasers have an option to buy another $20M in notes (4/14) Protein Polymer Technologies Inc. (OTC BB:PPTI) Private placement of stock and warrants 23.59S and 1 1.79W $7.75 The stock was priced at $0.33 per share; the fouryear warrants are exercisable at $0.50 per share; Luther Capital Management LLC and Palladium Capital Advisors LLC assisted in the deal, which was made in two closings (4/1 and 4/18) Proteome Sciences plc (UK; LSE:PRM) Private placement of stock 8.09S £4.7 ($8.8) Shares representing 6.6% of the company were placed with an institutional investor at 59.5 pence each (4/1) Provectus Pharmaceuticals Inc. (OTC BB: PVCT) Private placement of convertible debentures and warrants N/A and 4.2W $3.15 Investors led by Network 1 Financial Securities Inc. and DC Opportunity Fund Ltd. can convert the debt into stock at $0.75 per share; they also got five-year warrants to buy 4.2M shares at $1.06 per share (4/3) 66 Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Solexa Inc. (SLXA) Private placement of stock and warrants 2.1S and 1.1W $8.4 A second closing on the same terms bringing the total financing to $32.5M is expected later in 2005; the shares were sold at $4 each and the warrants are exercisable at $5 per share; the financing was led by ValueAct Capital (4/22) Unigene Laboratories Inc. (OTC BB: UGNE) Private placement of stock and warrants 2.123S and 1.062W $3 Fusion Capital Fund II LLC purchased the shares and the five-year warrants exercisable at $1.77 per share; following the deal Unigene terminated the stock purchase agreement with Fusion (4/13) ViroPharma Inc. (VPHM) Private placement of convertible notes N/A $12.5 Investors in an October 2004 deal exercised their option to buy another $12.5M in 6% notes due in October 2009; they are convertible into common stock at $2.50 per share; the sale totaled $75M (4/6) Alizyme plc (UK; LSE:AZM) Private placement and open offer 32.8S £32.8 ($56) The open offer consisted of 30.5 shares; Quintiles Transnational Corp. purchased 2.3M shares in a private placement (5/16) Altachem Pharma Ltd. (Canada; CDNX:AAF) Private placement of stock and warrants 4.2S and 2.1W C$1.05 ($0.84) Altachem closed the second tranche of a financing that totaled C$1.49M; the shares sold at C$0.25 each, and the one-year warrants are exercisable at C$0.45 per share (5/10) Amarin Corp. plc (UK; AMRN) Private placement of stock 13.7S $17.8 Amarin sold American depository shares in a registered direct offering; 3.5M of the shares were purchased by company directors and officers; Leerink Swann & Co. was placement agent (5/25) AspenBio Inc. (OTC BB:APNB) Private placement of stock and warrants 3.51S and 3.51W $3.07 Warrants issued in the deal are exercisable for five years at $1.35 per share (5/6) Australian Rights issue Cancer Technology Ltd. (Australia; ASX:ACU) 43.8S A$5.7 ($4.3) The shares were sold at A$0.13 each in a rights issue that was fully underwritten by BBY Ltd.; the company also changed its name to Avantogen Ltd. (5/17) Cellegy Private Pharmaceuticals placement of Inc. (CLGY) stock and warrants 3.636S and 0.545W $6 SJ Investments LLC, Tisch Family Interests, Kingsway LLC, Greenway Capital and Kingsbridge Capital Ltd. invested in the financing; the shares were sold at $1.65 each; half the five-year warrants are exercisable at $2.25 per share, and half at $2.50; C.E. Unterberg, Towbin was placement agent (5/13) MAY BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 67 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Corgenix Medical Corp. (OTC BB:CONX) Private placement of convertible notes and warrants N/A and 7.7W $3.42 The convertible notes are due in 2008; investors included Truk International Fund LP, Truk Opportunity Fund LLC and DCOFI Master LDC; they have a nine-month option to invest a further $1.5M; the warrants are convertible into stock at $0.25 per share (5/23) Dyax Corp. (DYAX) Private placement of stock 6.315S $25.26 The shares were sold from a shelf registration at $4 each; Deutsche Bank Securities Inc. and SG Cowen & Co. LLC were placement agents (5/19) GlycoGenesys Inc. (GLGS) Private N/A placement of convertible stock and warrants $4.5 The $4.5M is the second tranche of a financing; the first $2M was raised in March; the company sold 4,500 shares of convertible, redeemable Series D preferred stock, currently convertible into 4.5M shares of common stock, and warrants to purchase 4.5M shares at $1.23 each (5/23) Hybridon Inc. (AMEX:HBY) Private placement of convertible notes N/A $5 The 4% notes due 2008 initially are convertible into common stock at $0.89 per share (5/20) InSite Vision Inc. (AMEX:ISV) Private placement of stock and warrants 16.4S and 4.9W $9 The shares were sold at $0.55 each; the five-year warrants are exercisable at $0.6325 per share; Paramount BioCapital Inc. was placement agent (5/9) MacroPore Biosurgery Inc. (FSE:XMP) Private placement of stock and warrants 1.1S and 2.2W $1 1 The shares were sold at $10 each; the investor has an option to purchase 2.2M shares at $10 each until Dec. 31, 2006 (5/2) Millenia Hope Inc. (OTC BB: MLHP) Private placement of stock ND $0.6 The investment completes the first stage of an anticipated much larger private placement being arranged by Private Consulting Group Inc. (5/10) Miravant Medical Technologies Inc. (OTC BB:MRVT) Private placement of stock and warrants ND $8 Scorpion Capital Partners LP led the financing, which entailed the sale of preferred stock convertible into common stock at $1 per share; the same number of warrants also are convertible at $1 per share (5/4) NexMed Inc. (NEXM) Private N/A and placement of 1.19W convertible stock and warrants $4.45 445 shares of preferred stock were sold at $10,000 per share and initially are convertible into common stock at $1.36 per share; NexMed has certain quarterly rights to convert the stock at a 4.5% discount to the price at the time; the four-year warrants are exercisable at $1.43 per share (5/18) 68 Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) NovaDel Pharma Inc. (AMEX:NVD) Private placement of stock and warrants 6.7S and 2.4W $7 The financing was led by ProQuest Investments and included the Caisse de depot et placement du Quebec and others; the five-year warrants are exercisable at $1.30 per share (5/27) Oragenics Inc. (AMEX:ONI) Private placement of stock N/A $9 Fusion Capital Fund II LLC agreed to purchase up to $9M in stock over 30 months, at times and amounts to be determined by Oragenics; the comany has an option for another $9M investment following completion of the initial funding (5/24) Phytopharm plc (UK; LSE:PYM) Private placement and open offer 8.08S £10.1 ($18.9) Canaccord Capital Ltd. underwrote the placement and open offer; shares were issued at £1.25 each (5/4) Protalex Inc. (OTC BB: PRTX) Private placement of stock and warrants 2.6S and 0.787W $5.1 The shares were placed at $1.95 each; terms of the warrants were not disclosed; the financing was led by vSpring Capital (5/31) Senesco Technologies Inc. (AMEX:SNT) Private placement of stock and warrants 1.6S and 0.798W $3.37 Warrants issued in the deal are exercisable at $3.38 per share; Oppenheimer & Co. Inc. was placement agent (5/4) Acura Bridge loan Pharmaceuticals Inc. (OTC BB:ACUR) N/A $1 The one-year, 10% loan was provided by Essex Woodlands Health Ventures V LP and funds from Care Capital and Galen Partners (6/22) Advanced Magnetics Inc. (AMEX:AVM) Private placement of stock and warrants 1.8S and 0.36W $17.1 Shares in the registered direct sale were priced at $9.50 each; warrants are exercisable at $13 per share; investing were affiliates of Great Point Partners LLC and Vivo Ventures LLC, and a company director; the deal closed in two tranches (6/1 and 6/2) Aeolus Private Pharmaceuticals placement of Inc. (OTC BB:AOLS) convertible notes and warrants N/A and ND $2.5 The 6% notes are convertible into shares at $1 per share, as are the five-year warrants that accompanied them; the company has an option to pay the dividend in cash or shares; investors included Xmark Opportunity Funds and Biotechnology Value Fund LP (6/27) Auxilium Private Pharmaceuticals placement of Inc. (AUXL) stock and warrants 8.2S and 2.06W $40.4 The shares were sold at about $4.90 each, and the warrants are exercisable at $5.84 per share; Deutsche Bank Securities Inc. was lead placement agent (6/29) JUNE BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 69 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Bavarian Nordic A/S (Denmark; CSE: BAVA) Rights issue 1.16S DKK416.7 ($67.5) Among those participating in the fully subscribed rights issue were existing shareholders A.J. Aamund A/S and LD Pensions (6/23) BioDelivery Sciences International Inc. (BDSI) Convertible debt deal N/A $2.5 Laurus Master Fund Ltd., in a deal very similar to one completed in February with BDSI, bought a three-year, prime-plus-2% note convertible into common stock at $3.10 per share; Laurus also got warrants to purchase up to 483,871 shares at $3.88 per share (6/3) Bionomics Ltd. (Australia; ASX:BNO) Private placement of stock 44.4S A$6 ($4.6) Each share includes two-thirds of an option on an additional share at A$0.22 per full share; Intersuisse Corporate Pty. Ltd. managed the deal (6/27) BioTie Therapies Oyj (Finland; HSE: BTH1V) Private placement of stock 8.77S €6.6 ($8) Among investors subscribing in the stock sale were Juha Jouhki, Thominvest Oy, Dreadnought Finance Oy and BioFund Ventures III (6/22) Cephalon Inc. (CEPH) Private placement of convertible notes N/A $800 The 2% senior subordinated notes due 2015 are convertible at $46.70 per common share; the total does not include $120M in notes purchased per the underwriters’ overallotment option on July 1; the notes were sold from a shelf registration (6/2) CombiMatrix Group (CBMX) Private placement of stock 1.3S $2.9 The stock was sold from a shelf registration in a registered direct offering at $2.25 per share (6/30) Corautus Genetics Inc. (VEGF) Private placement of stock and loan agreement 4.7S $23 Boston Scientific Corp. and a group of private investors are purchasing 4.7M shares for $18M; separately, an amended loan deal with Boston Scientific makes $5M available to Corautus (6/28) Critical Therapeutics Inc. (CRTX) Private placement of stock and warrants 9.95S and 3.48W $54.5 Institutional and other accredited investors bought the shares at $5.48 each; the five-year warrants are exercisable at $6.58 per share (6/7) Crucell NV (the Netherlands; CRXL) Private placement of stock 3.6S €52.2 ($64) Crucell sold the shares at €14.50 each in a private placement; Fortis Bank was the sole manager in the deal (5/10) 70 Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) CV Therapeutics Inc. (CVTX) Public offering of convertible notes N/A $130 The 3.25% convertible senior subordinated notes due 2013 were sold in a public offering; they are convertible into stock at about $27 per share; underwriters were Lehman Brothers, Merrill Lynch & Co., Citigroup and Deutsche Bank Securities; the total does not include the July 1 purchase of $19.5M in notes per the underwriters’ overallotment option (6/29) Evotec AG (Germany; FSE:EVT) Private placement of stock 10.46S €28.4 ($34.5) Evotec sold the shares in a fully subscribed placement at €2.72 per share (6/24) Exelixis Inc. (ELEX) Funding vehicle N/A $40 Symphony Capital Partners provided $40M for further development of XL647, XL999 and XL784; it formed Symphony Evolution Inc., which has an option to call an additional $20M to $40M within one year (6/13) Galapagos NV (Belgium; Euronext:GLPG) Warrants exercise 0.082S €0.4 ($0.5) Galapagos placed 82,562 shares in connection with the exercise of warrants, which closed at the same time as it completed its €22M IPO (6/3) Generex Biotechnology Corp. (Canada; GNBT) Private placement of convertible notes and warrants N/A and 2.44W $2 Holders of 6%, 15-month notes purchased in 2004 bought another $2M in notes; they initially are convertible into stock at $0.60 per share; investors also got five-year warrants to purchase 2.44M shares at $0.82 each (6/16) Helix BioMedix Inc. (OTC BB:HXBM) Warrants exchange 4.95S $1.5 Warrants for the purchase of about 9.95M shares were properly tendered in the offer, which expired on May 31 (6/1) Hollis-Eden Private Pharmaceuticals placement of Inc. (HEPH) stock and warrants 1.33S and 0.267W $10 A single institutional investor purchased the shares at $7.50 each; the four-year warrants are exercisable at $10 per share; Rodman & Renshaw LLC was placement agent (6/1) Immunicon Corp. (IMMC) Private placement of stock 4.138S $19.7 The shares were sold from a shelf registration at $4.75 each; Legg Mason Wood Walker Inc. was lead placement agent; First Albany Capital Inc. was coplacement agent (6/30) Invitrogen Corp. (IVGN) Private placement of convertible notes N/A $350 The 3.25% senior convertible notes due 2025 were sold to institutional buyers; the total includes their purchase of $25M in notes per their option; the notes are convertible in some circumstances into cash or stock at an initial price of $98.25 per share (6/14) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Investors; Placement Agents; Details (Date) 71 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Lev Private Pharmaceuticals placement of Inc. (OTC BB:LEVP) stock and warrants 5.04S and 2.52W $5.04 The securities were sold as units priced at $50,000 each; the five-year warrants are exercisable at $1.35 per share; placement agent Laidlaw & Co. (UK) Ltd. also received 681,044 warrants exercisable at $1.35 per share (6/6) Peregrine Private Pharmaceuticals placement of Inc. (PPHM) stock 8S $6.72 The shares were sold from a shelf registration to a single investor (6/23) PharmaFrontiers Corp. (OTC BB:PFTR) Private placement of stock and warrants 3.387S and 9.3W $5.08 Investors purchased about 3.387M units at $1.50 per unit; each unit comprises one share of common stock and three types of warrants to purchase 2.75 shares at undisclosed prices (6/20) Procyon Biopharma Inc. (Canada; TSE:PBP) Private placement of convertible notes N/A C$3.5 ($2.8) The five-year, 7% notes are convertible into stock at $0.45 per share; investors also got warrants equal to 50% of the number of shares that could be issued; investors included Desjardins Venture Capital, Fonds Bio-Innovation and Societe Innovatech Quebec et Chaudieres-Appalaches; Dundee Securities Corp. was placement agent (6/30) RegeneRx BioPrivate pharmaceuticals placement of Inc. (AMEX:RGN) stock 1.538S $5 Affiliates of Sigma-Tau Group purchased the shares at $3.25; Sigma-Tau owned about 30% of RegeneRx before the deal (6/23) Tm Bioscience Corp. (Canada; TSE:TMC) Warrants exercise ND C$3.8 ($3.1) The warrants were issued in two private placements in 2003; any remaining warrants relating to those financings have now expired (6/29) Tripep AB (Sweden; SSE: TPEP) Rights issue and warrants placement 5.08S and 2.54W SEK28 ($3.6) Dormant Properties AB underwrote shares not taken up by existing shareholders and retained its 21% stake; warrants are exercisable at SEK8 and SEK12 per share (6/17) Tripep AB (Sweden; SSE: TPEP) Private placement of stock 0.256S SEK2.18 ($0.29) A private investor purchased the shares at SEK8.50 each, and agreed to exercise all preference rights on the shares in the upcoming rights issue (6/10) Valentis Inc. (VLTS) Private placement of stock and warrants 1.68S and 0.84W $4.2 The stock and warrants were sold as a unit at $2.50 per unit; the five-year warrants are exercisable at $3.51 per share (6/27) Viventia Biotech Inc. (Canada; TSE:VBI) Bridge loans N/A C$4.8 ($3.9) Viventia Chairman Leslie Dan provided loans of C$1.5M, C$1.5M and C$1.8 that carry a 4.5% annual interest rate (6/17) 72 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Xechem Sale of International minority Inc. (OTC BB:XKEM) interest N/A $2.3 Xechem sold most of its interest in CepTor Corp., which it spun off in February; CepTor purchased the shares; Xechem still has 500,000 CepTor shares, or 15% of its original investment (6/29) Zeltia SA (Spain; SPE:ZEL) Private placement of stock 10.75S €65 ($78.5) The shares were sold at €6.05 each; proceeds will be used to fund work at subsidiary PharmaMar SA; HSBC Securities was placement agent (6/23) Active Biotech AB (Sweden; SSE:ACTI) Rights issue 5.62S SKK169 ($21.5) About 98.5% of the shares offered were subscribed to based on subscription rights; the shares were purchased at SEK30 each (7/7) Adherex Technologies Inc. (AMEX:ADH) Private placement of stock and warrants 30.39S and 9.1W $8.5 The shares were sold at $0.28 each and the threeyear warrants are exercisable at $0.35 per share; GlaxoSmithKline plc invested $3M in the deal; Leerink Swann & Co. and Versant Partners Inc. were placement agents (7/20) Adventrx Private Pharmaceuticals placement of Inc. (AMEX:ANX) stock and warrants 10.81S and 10.81W $20 Investment funds controlled by Carl Icahn led the financing, which also included Viking Global Investors LP; the warrants are exercisable at $2.26 per share; CIBC World Markets was lead placement agent and RBC Capital Markets was co-agent (7/22) AspenBio Inc. (OTC BB:APNB) Private placement of stock and warrants 0.56S and 0.56W $0.49 The deal was the second closing of a financing that totaled about $3.6M; the five-year warrants are exercisable at $1.35 per share; Westminster Securities Corp. was placement agent (7/12) BioDelivery Sciences International Inc. (BDSI) Funding agreement N/A $7 Clinical Development Capital LLC will provide up to $7M in funding for Phase III trials of BDSI’s BEMA Fentanyl product in exchange for a milestone payment and royalties on product sales (7/18) Cel-Sci Corp. (AMEX:CVM) Private placement of stock and warrants 1.25S and 0.375W $0.5 A single investor purchased the stock at $0.40 per share; warrant terms were not disclosed (7/19) Cephalon Inc. (CEPH) Private placement of convertible notes N/A $120 Underwriters exercised their option on another $120M in notes, bringing gross proceeds from the sale to $920M; the 2% notes due 2015 are convertible at $46.70 per common share; the notes were sold from a shelf registration (7/1) JULY BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 73 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) CV Therapeutics Inc. (CVTX) Public offering of convertible notes N/A $19.5 Underwriters exercised their option on another $19.5M in notes, bringing total proceeds from the public offering to $149.5M; the 3.25% notes due 2013 are convertible into stock at about $27 per share; underwriters were Lehman Brothers, Merrill Lynch & Co., Citigroup and Deutsche Bank Securities (7/1) Cytogen Corp. (CYTO) Private placement of stock and warrants 3.1S and 0.776W $14 Shares in the registered direct offering were sold at $4.50 each; the warrants are exercisable at $6 per share; the deal was made from an existing shelf registration (7/19) GeneMedix Private plc (UK; LSE:GMX) placement of stock and warrants 4.31S and 2.16W £0.281 ($0.5) The funding is the second $0.5M taken from a potential total of $10M over three years from funds advised by Southridge Management LLP; the threeyear warrants are exercisable at 7.25 pence per share (7/14) Genentech Inc. (NYSE:DNA) Private placement of notes N/A $2B Genentech priced $500M of 4.4% notes due 2010, $1B of 4.75% notes due 2015, and $500M of 5.25% notes due 2035 (7/13) Isotechnika Inc. (Canada; TSE:ISA) Bought-deal financing 8.9S C$20 ($16.6) A syndicate of underwriters led by GMP Securities Ltd. and including Canaccord Capital Corp., National Bank Financial Inc. and TD Securities Inc. purchased the shares at C$2.25 each; the totals include the exercise of their overallotment option (7/12) Labopharm Inc. (Canada; TSE:DDS) Debt financing N/A $10 Hercules Technology Growth Capital Inc. provided an 1 1.95% loan repayable on July 1, 2008; Hercules also got five-year warrants to purchase 543,104 Labopharm shares at $2.71 each (7/1 1) Neurochem Inc. (Canada; NRMX) Warrants exercise 2.8S C$8.8 ($7.1) Picchio Pharma Inc. exercised a warrant from a July 2002 private placement to purchase 2.8M shares; Picchio Pharma now owns about 26.4% of Neurochem (7/25) Novavax Inc. (NVAX) Private placement of stock 4S $4 The shares were sold from a shelf registration at $1 each; Lane Capital Markets LLC was placement agent (7/5) 2.47S $8.47 The shares were sold at $3.43 each, a 15% discount to a five-day average; Jefferies & Co. Inc. was the placement agent (7/28) Pharmacopeia Private Drug Discovery placement of Inc. (PCOP) stock 74 Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) ReGen Biologics Inc. (OTC BB: RGBI) Private placement of stock and warrants 13.9S and 3.48W $1 1.8 The shares were sold at $0.85 each; the five-year warrants are exercisable at $1 per share (7/15) Sirna Therapeutics Inc. (RNAI) Private placement of stock and warrants 17.5S and 6.3W $28 The shares were sold at $1.60 each and the warrants are exercisable at $1.92 per share until July 2010; investors included Sprout Group, Oxford Bioscience Partners and Venrock Associates; Thomas Weisel Partners was placement agent, and Leerink Swann and Brean Murray were co-advisers (7/7) Solexa Inc. (SLXA) Private placement of stock and warrants 6S and 3W $24 The financing was the second closing of a $32.5M round; the first part closed in April; the shares were sold at $4 each and the warrants are exercisable at $5 each; investors included Abingworth Management Ltd., Amadeus Capital Partners Ltd., Oxford Bioscience Partners and SV Life Sciences; SG Cowen & Co. LLC was placement agent (7/12) SR Pharma plc (UK; AIM:SRA) Private placement of stock 36.1S £8.3 ($14.6) Separately, Introgen Therapeutics Inc. invested $3M in SR Pharma as part of a collaboration; Mulier Capital Ltd. was financial adviser for the placement (7/28) Stem Cells Sciences plc (UK; AIM:STEM) Private placement of stock 6.2S £6 ($10.5) Stem Cells gained a public listing on the Alternative Investment Market in the financing; Collins Stewart plc brokered the deal (7/14) Synthetic Blood International Inc. (OTC BB:SYBD) Private N/A and placement of 8.4W convertible debt and warrants $1.85 Terms of the convertible debentures were not disclosed; the three-year warrants are exercisable at $0.242 per share; the investment was led by Palisades Master Fund and arranged by HPC Capital Management LLC (7/13) Transgene SA (France; TRGNY) Private placement of stock and warrants 4.66S and 2.33W €34.9 ($42.2) Most of the shares were placed in Europe; the oneyear warrants are exercisable at €8.05 per share (7/1 1) Xenomics Inc. (OTC BB:XNOM) Private placement of convertible stock and warrants N/A and 0.387W $2.77 The Series A convertible stock is convertible into common stock at $2.15 per share; the five-year warrants are exercisable at $3.25 per share (7/15) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Investors; Placement Agents; Details (Date) 75 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Allon Therapeutics Inc. (Canada; CDNX:NPC) Private placement of stock 6S C$6.3 ($5.3) The shares were sold at C$1.05 each; as part of the deal about 2.5M previously issued warrants were redeemed for C$0.05 each (8/29) AMDL Inc. (AMEX:ADL) Private placement of stock and warrants 3.164S and 1.9W $1 The financing had two closings; shares were sold at $0.32 and $0.315 each; the three-year warrants are exercisable at $0.49 and $0.48 per share; Galileo Asset Management SA and Havkit Corp. were placement agents (8/18 and 8/30) Astralis Ltd. (OTC BB:ASTR) Private placement of stock and warrants 18.18S and ND $2 Blue Cedar Ltd. purchased the shares at $0.1 1 each; warrant terms were not disclosed; a second closing in the round was expected in September (8/19) Biotech Holdings Ltd. (Canada; OTC BB: BIOHF) Private placement of stock 0.419S and 0.419W C$0.12 ($0.1) A company insider purchased the shares at C$0.29 each; the warrants are exercisable at C$0.39 each (8/10) Boston Life Sciences Inc. (BLSI) Private placement of stock 6S $12.78 The shares were sold at $2.13 each; Robert L. Gipson was expected to own 19.9% of the company following the stock sale (8/30) Callisto Private Pharmaceuticals placement of Inc. (AMEX:KAL) stock 1.87S $1.81 Existing shareholders purchased the stock at $0.97 per share (8/23) Coley Pharmaceutical Group Inc. (COLY) Private placement of stock 0.625S $10 Pfizer Inc. purchased the shares privately in a deal concurrent with the company’s initial public offering; the shares were purchased at the $16 IPO price (8/10) Genta Inc. (GNTA) Private placement of stock 19.1S $17.5 The shares were sold from an existing registration statement; Piper Jaffray & Co. was placement agent (8/8) GTC Private Biotherapeutics placement of Inc. (GTCB) stock and warrants 4.57S and 1.8W $8 The shares were sold at $1.75 each; the five-year warrants are exercisable at $2.68 per share; Rodman & Renshaw LLC was placement agent (8/8) Human Genome Private Sciences Inc. placement of (HGSI) convertible notes N/A $230 The 2.25% subordinated notes due 20 1 2 are convertible into common stock at $17.78 per share (8/4) AUGUST 76 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) International Medical Innovations Inc. (Canada; TSE:IMI) Bought-deal placement of units N/A C$10 ($8.4) Each unit comprised a $1,000 principal amount 7% convertible debentures and 157 common-share purchase warrants; each four-year warrant is convertible into common stock at $2.85 per share (8/18) Inhibitex Inc. (INHX) Private placement of stock 5S $41.25 Institutional investors purchased the shares at $8.25 each; Lazard Capital Markets LLC was placement agent (8/18) InNexus Biotechnology Inc. (Canada; OTC BB:ISXBF) Private placement of securities N/A $3.05 The company raised $2.5M through the sale of 8% to 12% notes convertible into 10M shares and 10M $0.25 warrants; it also got a $0.25M bridge loan, and it raised $0.3M through the placement of 1.2M shares and 1.2M $0.30 warrants (8/8) Isis Private Pharmaceuticals placement of Inc. (ISIS) stock and warrants 12S and 3W $51 The shares were sold at $4.25 each, and the warrants are exercisable at $5.23 per share; Needham & Co. and Fortis Securities LLC were placement agents (8/22) Kamada Ltd. Initial offering (Israel; TEL:KMDA) of stock 1.875S NIS30 ($6.7) Kamada completed an initial public offering on the Tel Aviv Stock Exchange; the offering was underwritten by Poalim IBI, Clal Finance Underwriting, Altshouler-Shacham and Rosario Capital (8/17) Large Scale Biology Corp. (LSBC) Bridge loan N/A $1 Two company officials provided $1M in a term-loan deal, which also included the issuance of warrants; separately, it entered a deal under which it can sell $15M in stock to Brittany Capital over three years (8/8) Manhattan Pharmaceuticals Inc. (OTC BB: MHTT) Private placement of stock and warrants 10.76S and 2.15W $1 1.9 The shares were sold at $1.1 1 each; the five-year warrants are exercisable at $1.44 per share; Paramount BioCapital Inc. was placement agent (8/30) MannKind Corp. (MNKD) Private placement of stock and warrants 17.1S and 3.4W $175 Half the money was invested by institutional investors and half by MannKind Chairman and CEO Alfred Mann; the warrants are exercisable at $12.228 per share; Wachovia Securities and Leerink Swann & Co. were placement agents (8/3) Medicure Inc. (Canada; TSE: MPH) Private placement of stock and warrants 5.21S and 2.6W $3.85 The shares were sold at $0.74 each; the five-year warrants are exercisable at $0.97 per share; Satellite Asset Management LP led the placement; Needham & Co. was placement agent (8/22) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Investors; Placement Agents; Details (Date) 77 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) MIV Therapeutics Inc. (Canada; OTC BB:MIVT) Private placement of securities ND $4.14 Details on the non-brokered private placement were not disclosed (8/22) Nektar Therapeutics (NKTR) Private placement of stock and warrants 1.436S and 0.45W $24 The shares were sold from a shelf registration at $16.71 to Mainfield Enterprises Inc., which also got a 15-month option to purchase additional shares (8/16) Nutra Pharma Corp. (OTC BB: NPHC) Private placement of stock and warrants 24S and 6W $9.6 SBI Brightline XII LLC is obligated to buy, upon Nutra Pharma’s election, up to 24M shares of common stock; the warrants are exercisable from $0.30 to $0.50 per share (8/18) Peplin Ltd. (Australia; ASX: PEP) Private placement of stock 1 1.4S A$4 ($3.1) Shares in the placement were sold at A$0.35 each; shareholders also received the right to purchase shares at that price through Aug. 26 (8/2) pSivida Ltd. (Australia; PSDV) Private placement of stock and warrants 6.5S and 0.65W $4.23 The company sold 650,000 American depository receipts at $6.50 each; each ADR represents 10 ordinary shares; the 3-year warrants are exercisable at $12.50 per ADR (8/24) Regeneration Technologies Inc. (RTIX) Private placement of stock 2.8S $23.9 The shares were sold at $8.55 each; Pacific Growth Equities LLC was placement agent (8/29) ReNeuron Group plc (UK; AIM:RENE) Private placement of stock and warrants 38S and 19W £9.5 ($17.2) ReNeuron gained a listing on AIM along with the placement in the UK and U.S.; shares were sold at 25 pence each; the warrants are exercisable at 30 pence each; Collins Stewart and Harris Nesbitt Corp. were agents in the deal (8/5) Rexahn Pharmaceuticals Inc. (OTC BB: RXHN) Private N/A and placement of 4.175S convertible notes and stock $9.65 The three-year notes are convertible into common stock at $2 per share; the shares were sold at $2 each (8/1 1) Santarus Inc. (SNTS) Private placement of stock $31.2 The shares were sold from a shelf registration at $4.25 each; SG Cowen & Co. LLC was lead placement agent and RBC Capital Markets Corp. was coplacement agent (8/17) 78 7.35S Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Sonus Private Pharmaceuticals placement of Inc. (SNUS) stock and warrants 4.65S and 2.33W $16.8 Shares were purchased at $3.77 each; for another $0.125 per underlying share, investors also got five-year warrants exercisable at $4.15 per share; investors included Domain Public Equity Partners, Efficacy Capital, MPM BioEquities, ProMed and Heights Capital Management; Punk Ziegel & Co. was placement agent (8/16) Vaso Active Private Pharmaceuticals placement of Inc. (PK:VAPH) convertible notes and warrants N/A and 1.3W $2.5 The $2.5M in notes due May 2007 are convertible into stock at $0.70 per share; the five-year warrants are exercisable at $0.77 per share; investors also have a right to purchase another $1.88M in notes and 974,026 warrants (8/16) Viventia Biotech Inc. (Canada; TSE:VBI) Bridge loans N/A C$3.3 ($2.75) Viventia Chairman Leslie Dan provided loans totaling C$3.3; they carry a 4.5% annual interest rate (8/12) Vyteris Holdings Inc. (OTC BB:VYHN) Private N/A and placement of 2.08W convertible notes and warrants $10 The three-year, 8% notes are convertible into common stock at $2.40 per share; the warrants are exercisable at $2.88 per share; investors have an option to invest another $5M on those terms (8/19) Xenogen Corp. (XGEN) Private placement of stock and warrants 5.155S and 1.55W $15 The shares were sold at $2.91 each and the warrants are exercisable at $3.29 per share; Thomas Weisel Partners LLC was placement agent (8/1 1) Acacia ResearchCombiMatrix (CBMX) Private placement of stock and warrants 6.4S and 1.6W $10.5 The shares were sold in a registered direct offering at $1.65 each; the five-year warrants are exercisable at $2.40 per share; Piper Jaffray & Co. was placement agent (9/16) Advanced Cell Technology Inc. (OTC BB: ACTC) Private placement of convertible notes and warrants N/A and 4.84W $17.75M The three-year notes are convertible into 9.67M shares of stock at $2.30 per share; the five-year warrants are exercisable at $2.53 per share; T.R. Winston & Co. was placement agent (9/16) Ascentia Biomedical Corp. (PK:ASCE) Private placement of convertible notes N/A $1 Winsted Holdings Inc. committed to purchase up to $1M in a series of convertible notes; terms were not disclosed (9/14) Emisphere Technologies Inc. (EMIS) Loan N/A $15 The senior secured loan was provided by MHR Fund Management LLC; the loan may be exchanged for a note convertible into stock (9/26) SEPTEMBER BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 79 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) Genaera Corp. (GENR) Private placement of stock and warrants 1 1.4S and 3.42W $24.5 The registered stock was purchased at $2.15 per share; the warrants are exercisable at $3.15 per share; RBC Capital Markets Corp. was lead placement agent and Fortis Securities LLC was co-agent (9/12) GenVec Inc. (GNVC) Private placement of stock 7.65S $15.3 Shares in the registered direct offering were sold at $2 each; SG Cowen & Co. LLC was placement agent (9/21) Geron Corp. (GERN) Warrant exercise 2S $18 Merck & Co. Inc. exercised a warrant to purchase 2M shares of stock at $9 each; the deal was made concurrent with Geron’s public offering of 6M shares priced at $9 each (9/16) Inflazyme Restructuring Pharmaceuticals of subsidiary Inc. (Canada; TSE:IZP) N/A C$3.4 ($2.9) Inflazyme realized C$3.4M from the sale of convertible debentures by the subsidiary; a put agreement to sell its holdings in the subsidiary could bring Inflazyme another C$2.5M by March 15, 2006 (9/20) Lipid Sciences Inc. (LIPD) 2.43S and 1.94W $7.2 The shares were sold at $2.98 each; 62.5 of the warrants are exercisable at $3.73 per share; the remaining warrants are exercisable for five years at $4.20 per share; A.G. Edwards was placement agent (9/29) Memory Private Pharmaceuticals placement of Corp. (MEMY) stock and warrants 16.1S and 5.6W $30.6 The shares were sold at $1.90 each; the warrants are exercisable at $2.22 per share (9/21) Nanogen Inc. (NGEN) Private placement of stock and warrants 6.8S and 1W $20 Institutional investors purchased the shares at $2.94 each; the five-year warrants are exercisable at $4 per share; Seven Hills Partners LLC was lead placement agent; Stonegate Securities Inc. was coplacement agent (9/28) Nektar Therapeutics (NKTR) Private placement of stock 0.455S $8 Mainfield Enterprises Inc., which invested $24M in Nektar in August, exercised its option from that deal to acquire an additional 454,803 shares (9/8) Nektar Therapeutics (NKTR) Private placement of convertible notes N/A $315 The 3.25 subordinated notes due 2012 are convertible into common stock at $21.52 per share; totals include the purchase of $40M in notes per the investors’ option (9/22) 80 Private placement of stock and warrants Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Optigenex Inc. (OTC BB:OPGX) Private placement of notes and warrants N/A and 0.625 $4 The three-year, 8 notes are convertible into stock at the lower of $3.20 or 40 of a 20-day trading average; terms of the five-year warrants were not disclosed (9/7) Spectrum Private Pharmaceuticals placement of Inc. (SPPI) stock and warrants 8S and 4W $42 The shares were sold from a shelf registration at $5.25 each; the six-year warrants are exercisable at $6.62 per share; Rodman and Renshaw LLC was placement agent (9/15) Transgenomic Inc. (TBIO) Private placement of stock and warrants 15S and 6W $15.15 Institutional investors led by Lehman Brothers bought the shares at $1.01 each; the warrants are exercisable at $1.20 per share (9/23) VaxGen Inc. (PK:VXGN) Sale of interest in subsidiary N/A $15 A group of South Korean investors purchased part of VaxGen’s stake in Celltrion Inc., reducing VaxGen’s stake in the South Korean manufacturing operation to 22.2 from 26.9 (9/21) York Pharma plc (UK; AIM:YRK) Private placement of stock 4.717S £5 ($9) The shares were placed at 106 pence each with institutional and other investors (9/16) Avanir Private Pharmaceuticals placement of Inc. (AMEX:AVN) stock 6.1S $16.15 Shares were sold at $2.65 each in a registered direct offering from a shelf registration; investing were Xmark Funds, Federated Kaufmann, Jennison Associates LLC and OrbiMed Advisors LLC (10/18) CepTor Corp. (OTC BB:CEPO) Stock purchase agreement N/A N/A Fusion Capital Fund II LLC agreed to purchase up to $20M of CepTor common stock over 40 months; CepTor has the right to sell Fusion $500,000 of stock per month at the market price (10/10) Cytokinetics Inc. (CYTK) Stock purchase agreement N/A N/A Kingsbridge Capital Ltd. committed to purchase up to $75M of Cytokinetics’ stock during the next three years, at times to be determined by Cytokinetics; Kingsbridge also got a five-year warrant to buy up to 244,000 shares at $9.13 per share (10/28) Forbes Medi-Tech Inc. (Canada; FMTI) Private placement of convertible notes and warrants 3.636S and 1.82W $6 The notes, which mature in October 2008, are convertible into about 3.6M shares at $1.65 per share; the five-year warrants are exercisable at $2.06 per share; Merriman Curhan Ford & Co. was placement agent (10/27) OCTOBER BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 81 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) Generex Biotechnology Corp. (Canada; GNBT) Warrants exercise ND $6.4 Investors paid $6.4M to exercise warrants to purchase an undisclosed number of shares (10/28) Gentium SpA (Italy; AMEX:GNT) Private placement of stock and warrants 1.55S and 0.62W $10.9 The American depository shares were sold at $7.05 each; warrants to ADSs are exercisable at $9.69 each; lead investors were funds managed by Great Point Partners LLC; Rodman & Renshaw LLC was lead placement agent; Maxim Group LLC and IBankers Securities Inc. were co-agents (10/4) GlycoGenesys Inc. (GLGS) Stock purchase agreement N/A N/A Fusion Capital Fund II LLC agreed to purchase up to $20M of GlycoGenesys stock over 25 months, at times determined by GlycoGenesys (10/24) Hana Biosciences Inc. (AMEX:HBX) Private placement of stock and warrants 3.68S and 0.737W $14.7 The shares were sold at $4 each; the five-year warrants are exercisable at $5.80 per share; investors included ProMed Management, Lehman Brothers, Pogue Capital Management, Perceptive Life Sciences Fund, Atlas Equity, Mosaix Ventures, Coqui Capital and Panacea Asset Management; Oppenheimer & Co. Inc. was lead placement agent and Griffin Securities was co-agent (10/19) Helix BioPharma Corp. (Canada; TSE:HBP) Private placement of stock and warrants 2.34S and 2.34W C$4 ($3.4) The securities were placed in Europe; each warrant is exercisable at C$2.39 per share until March 31, 2008 (10/4) Inflazyme Restructuring Pharmaceuticals of subsidiary Inc. (Canada; TSE:IZP) N/A C$3.6 ($3) Inflazyme raised a total of C$7M from the restructuring in September and then the sale of a subsidiary (10/27) La Jolla Pharmaceutical Co. (LJPC) Private placement of stock and warrants 88S and 22W $66 Investing in the deal were Essex Woodlands Health Ventures Fund VI LP, Frazier Healthcare Ventures, Alejandro Gonzalez, Special Situations Funds, Domain Public Equity Partners LP and Sutter Hill Ventures; the five-year warrants are exercisable at $1 per share (10/7) Metabasis Therapeutics Inc. (MBRX) Private placement of stock and warrants 7S and 2.45W $41.3 The shares were sold at $5.86 each; the warrants are exercisable at $6.74 per share; investors paid an additional $0.125 per warrant; SG Cowen & Co. LLC was lead placement agent, and Rodman & Renshaw LLC served was co-agent (10/3) 82 Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) Mologen AG (Germany; FSE:MGN) Private placement of stock 0.684S €5.1 ($6.1) The shares were placed with Absolute Capital Management at a 10-day average market price, which was not disclosed; the amount raised was estimated (10/12) Novelos Therapeutics Inc. (OTC BB: NVLT) Private placement of convertible stock and warrants N/A and ND $3 The 8% notes are convertible into stock at $1.65 per share; the five-year warrants are exercisable at $5 per share (10/3) Ortec International Inc. (OTC BB: ORTN) Private placement of stock and warrants 13.2S and 6.6W $3.3 The shares were sold at $0.25 each; the warrants are exercisable at $0.50 per share (10/12) pSivida Ltd. (Australia; PSDV) Private placement of convertible notes and warrants N/A and 0.633W $15 The three-year, 8% notes are convertible into American depository receipts at $7.10 each; the six-year warrants are exercisable at $7.20 per ADR (10/6) Tercica Inc. (TRCA) Equity facility and warrant sale N/A and 0.26W N/A Kingsbridge Capital Ltd. committed to purchase up to $75M in stock over three years; Tercica will determine the timing and amounts; Kingsbridge also got a five-year warrant to purchase 260,000 shares at a 30% premium (10/14) Vasogen Inc. (Canada; VSGN) Private placement of convertible notes and warrants N/A and 3.33W $40 The two-year, 6.45% notes are convertible into common stock at $3 per share; the five-year warrants are exercisable at $3 per share (10/7) Vical Inc. (VICL) Private placement of stock 4.7S $22.6 The shares were sold at $4.80 each in a registered direct offering; Piper Jaffray & Co. was lead placement agent; Needham & Co. LLC and Rodman & Renshaw LLC were co-placement agents (10/12) VioQuest Pharmaceuticals Inc. (OTC BB: VQPH) Private placement of stock and warrants 1 1.2S and 4.5W $8.4 The shares were sold concurrently with its merger with Greenwich Therapeutics; the five-year warrants are exercisable at $1 per share; Paramount BioCapital Inc. was placement agent (10/19) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Investors; Placement Agents; Details (Date) 83 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Abcam plc (UK; AIM:ABC) Private placement of stock 6S £10 ($17.4) The shares were sold at 167 pence each; totals do not include £5.25 raised by selling shareholders; the company also gained a listing on the AIM; Numis Securities was placement agent (1 1/3) Angel Biotechnology Holdings plc (UK; AIM:ABH) Private placement of stock 136.4S £1.5 ($2.6) The company gained admission to the Alternative Investment Market in conjunction with the financing (1 1/1 1) AVI BioPharma Inc. (AVII) Private placement of stock 6.9S $22.6 The shares were sold from a shelf registration at $3.26 each in a direct placement; Rodman & Renshaw LLC was placement agent (1 1/14) BioInvent International AB (Sweden; SSE:BINV) Rights offering 17.685S SEK160 ($19.5) Shares were sold at SEK9 per share in the deal in which existing shareholders got preference rights (1 1/2) Carrington Laboratories Inc. (CARN) Private placement of notes and warrants N/A and 5W $5 The $5M in 6% notes are due in 2006; half the four-year warrants are exercisable at $5 per share and half at $10 per share (1 1/21) Cell Therapeutics Inc. (CTIC) Private placeN/A ment of convertible notes $82 The 6.75% senior notes due in 2010 are convertible into common stock at an initial price of $2.629 per share (1 1/1) Delcath Systems Inc. (DCTH) Private placement of stock and warrants 0.753S and 0.188W $2.5 H.C. Wainwright & Co. Inc. was placement agent for the deal, terms of which were not disclosed (1 1/28) Evolutec Group plc (UK; AIM:EVC) Private placement of stock 6.25S £10 ($17.3) The financing was fully underwritten by Robert W. Baird (1 1/1 1) GammaCan International Inc. (Israel; OTC BB:GCAN) Private placement of securities ND $0.5 Sal. Oppenheim Jr. & Cie. Ltd. invested in the deal and has an option to invest an additional $2M; terms were not disclosed (1 1/15) Helix BioPharma Corp. (Canada; TSE:HBP) Private placement of stock and warrants 3.156S and 3.156W C$5.52 ($4.65) The private placement was completed in Europe; the warrants are exercisable at C$2.45 until March 31, 2008 (1 1/7) NOVEMBER 84 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Of Amount Shares, Units Raised (M) Or Warrants (M) Javelin Pharmaceuticals Inc. (OTC BB: JVPH) Private placement of stock and warrants 14.22S and 0.71 1W $32 The financing was led by NGN Capital and funds affiliated with Wexford Capital LLC; the five-year warrants are exercisable at $2.25 per share; Rodman & Renshaw LLC and Riverbank Capital Securities Inc. were placement agents (1 1/3) Karo Bio AB (Sweden; SSE: KARO) Rights issue 46.4S SEK278.7 ($33.8) The rights issue was 98% subscribed with preferential right for the shareholders (1 1/14) Novavax Inc. (NVAX) Private placement of stock 4.186S $18 The stock was sold from a shelf registration at $4.30 per share; Rodman & Renshaw LLC was placement agent (1 1/2) Nymox Pharmaceutical Corp. (NYMX) Private placement of stock ND $13 The stock was priced at a 3% discount to the market price; further terms were not disclosed (1 1/2) Oragenics Inc. (AMEX:ONI) Private placement of stock and warrants 3S and 3W $1.2 The shares were sold at $0.40 each and the twoyear warrants are exercisable at $0.60 per share (1 1/21) Oxford Biomedica plc (UK; LSE:OXB) Private placement and open offer 120.3S £30.1 ($51.7) The deal was fully underwritten by Evolution Securities; shares were sold at 25 pence each; Sigma-Aldrich Corp. invested £2.9M; NM Rothschild & Sons was financial adviser in the deal (1 1/16) Peregrine Private Pharmaceuticals placement of Inc. (PPHM) stock 8S $6.7 The shares were sold to Double U Master Fund LP (1 1/23) Pharmaxis Ltd. (Australia; PXSL) Private placement of stock 19.9S A$43.8 ($32) The placement was completed with Australian and other investors concurrently with a public offering in the U.S., which raised another $31.4M (1 1/8) Pharmexa A/S (Denmark; CSE: PHARMX) Private placement of stock 3.4S DKK72.9 ($1 1.5) The shares were sold at DKK21.45 each, following a deal to acquire certain assets from IDM Pharma Inc.; ING was placement agent (1 1/24) Phoqus Group plc (UK; AIM: PQS) Private placement of stock 7.14S £10 ($17.5) Phoqus gained listing on the Alternative Investment Market through the sale of shares at 140 pence each; Code Securities underwrote the deal (1 1/3) Sangamo BioSciences Inc. (SGMO) Private placement of stock 5.08S $19.5 Institutional investors and Dow AgroSciences LLC purchased about 5.08M shares at $3.85 per share; JMP Securities and Piper Jaffray & Co. were lead placement agents; Leerink Swann & Co. was coplacement agent (1 1/1 1) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Investors; Placement Agents; Details (Date) 85 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number OF Amount Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) SemBioSys Genetics Inc. (Canada; TSE:SBS) Debt financing N/A C$2.5 ($2.1) The long-term debt financing was secured from Oxford Finance Corp. (1 1/21) SIGA Technologies Inc. (SIGA) Private placement of stock and warrants 2S and 1W $2 The shares were sold for $1 each, and the sevenyear warrants are exercisable at 1 10% of the Nov. 2 closing price; investors can purchase another $2M in stock at $1.10 per share; The Shemano Group was placement agent (1 1/3) Solexa Inc. (SLXA) Private placement of stock and warrants 10S and 3.5W $65 The shares were sold at $6.50 each, and the warrants are exercisable at $7.50 per share; about 60% of the deal will close after shareholder approval (1 1/21) Starpharma Holdings Ltd. (Australia; ASX:SPL) Private placement of stock and share purchase plan 29.4S A$15 ($1 1) The deal included an A$12M institutional placement and an A$3M underwritten share purchase plan; shares were priced at A$0.51 in both deals; Patersons Securities was lead agent in the placement and underwriter of the SPP (1 1/14) Stressgen Biotechnologies Corp. (Canada; TSE:SSB) Private placement of stock and warrants 7.645U C$2.68 ($2.3) Each unit consists of one share and one-third of a warrant; each full warrant is exercisable for two years to purchase one share at C$0.50 each; Canaccord Capital Corp. was placement agent (1 1/1) Viventia Biotech Inc. (Canada; TSE:VBI) Warrants exercise ND C$12 ($10) The Dan Group exercised C$12M in warrants; then the group was repaid C$12M owed in promissory notes; the Dan Group now owns more than 90% of the company and plans to acquire the rest (1 1/14) Acrongenomics Private Inc. (OTC BB: placement of AGNM) stock 1S $4 The shares were placed at $4 each (12/22) Alchemia Ltd. (Australia; ASX: ACL) 19.6S A$21.6 ($16.1) Shares were sold at A$1.10 to institutional investors in a private placement in November; another A$5M was raised through a subsequent sale of stock to shareholders at the same price (12/14) DECEMBER 86 Private placement of stock and share purchase plan BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number OF Amount Shares, Units Raised (M) Or Warrants (M) Amarin Corp. plc (UK; AMRN) Private placement of stock and warrants 26.1S and 9.1W $26.4 Amarin sold 26.1M American depository shares, each representing one common share, at $1.01 apiece; each warrant is exercisable at $1.43 per share; investors included Southpoint Capital Advisors LP, Biotechnology Value Fund LP, Fort Mason Capital LP and Domain Public Equity Partners LP (12/19) Amphion Innovations plc (AIM:AMP) Private placement of stock 3.6S £1 ($1.7) The shares were sold at 27.5 pence each (12/5) Antisoma plc (UK; LSE:ASM) Private placement of stock 33.6S £6.55 ($1 1.5) The shares were placed at 19.5 pence each in an oversubscribed deal; ING was placement agent (12/5) Avanir Private Pharmaceuticals placement of Inc. (AMEX:AVN) stock 6S $20 Shares in the registered direct offering were sold at $3.35 each to investors that included Federated Kaufmann; the deal was initiated through Leerink Swann & Co. (12/16) BioCryst Private Pharmaceuticals placement of Inc. (BCRX) stock 2.229S $30 Shares in the registered direct offering were sold at $13.46 each; investors included Kleiner Perkins Caufield & Byers and Texas Pacific Group Ventures (12/15) BioInvent International AB (Sweden; SSE:BINV) 47.16S SEK160 ($20.3) 26% of the shares were subscribed for without preferential rights in the oversubscribed deal (12/9) Bioniche Life Sale of Sciences Inc. various (Canada; TSE:BNC) securities N/A $18.5 The deal with Laurus Funds consisted of shares, debt, convertible debt and warrants, with about $17.5M of the total being various debt (12/9) BioTime Inc. (OTC BB:BTIM) Rights offer of stock and warrants 4.465S and 4.465W $1.8 Units consisting of one share and one warrant were sold at $0.40 each; the five-year warrants are exercisable at $2 per share (12/22) CepTor Corp. (OTC BB:CEPO) Private placement of convertible notes N/A $2 Cornell Capital Partners LP purchased the threeyear, 8% notes, which are convertible at the lesser of 105% of the price prior to the deal, or 95% of the lowest price for 20 days before conversion (12/15) Ceragenix Private Pharmaceuticals placement of Inc. (OTC BB:CGXP) convertible notes N/A $3.2 The two-year, 10% notes are convertible into stock at $2.05 per share; investors also got five-year warrants representing half the shares that are exercisable at $2.225 per share (12/6) Rights issue BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Investors; Placement Agents; Details (Date) 87 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Chiron Corp. (CHIR) Private placement of stock 6.9S $300 Novartis AG purchased the shares at $43.50 each under a subscription agreement between the companies; Novartis has offered to acquire all of Chiron (12/8) CollaGenex Private Pharmaceuticals placement of Inc. (CGPI) stock 2.9S $29 CollaGenex sold the shares at $10 each in a registered direct offering; Roth Capital Partners LLC was placement agent (12/21) Cytogen Corp. (CYTO) Private placement of stock and warrants 3.73S and 0.932W $13.3 The shares were sold at $3.56 each; the five-year warrants are exercisable at $4.25 per share; Rodman & Renshaw was placement agent (12/13) Discovery Laboratories Inc. (DSCO) Private placement of stock 3.03S $20 The shares were sold in a registered direct offering at $6.60 each; SG Cowen & Co. LLC was placement agent (12/14) GTC Private Biotherapeutics placement of Inc. (GTCB) stock and warrants 9.1S and 3.6W $16.7 Shares were sold for $1.78 each in the registered direct offering; investors also paid $0.125 per warrant; the five-year warrants are exercisable at $2.05 per share; SG Cowen & Co. LLC was lead placement agent; Rodman & Renshaw LLC was co-agent (12/8) Halozyme Therapeutics Inc. (AMEX:HTI) Private placement of stock and warrants 10S $17.5 The shares were sold in a registered direct offering at $1.75 each; SG Cowen & Co. LLC was lead placement agent; Rodman & Renshaw and Roth Capital Partners were co-placement agents (12/13) Immtech International Inc. (AMEX:IMM) Private placement of convertible stock and warrants N/A and 0.0835W $3.34 Immtech sold 133,600 Series E shares at $25 per share, with each convertible into 3.551 1 shares; the 83,500 three-year warrants are exercisable at $10 per share; investors have an option to purchase 25% more of the Series E shares (12/14) Inovio Private Biomedical placement of Corp. (AMEX:INO) stock and warrants 6.583S and 2.3W $15.8 Shares were sold at $2.40 each, and the five-year warrants are exercisable at $2.93 per share; a group of institutional investors was joined by Merck & Co. Inc. and Vical Inc. in the deal; Thomas Weisel Partners was placement agent (12/19) InSite Vision Inc. (AMEX:ISV) ND $4 The financing was obtained through Paramount BioCapital Inc.; terms of the deal were not disclosed; another $2M was expected to be invested early in January (12/30) 88 Private placement of debt and warrants Investors; Placement Agents; Details (Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Investors; Placement Agents; Details (Date) Lpath Private Therapeutics placement of Inc. (OTC BB:LPTN) stock and warrants 7.5S and 0.375W $6 The deal was completed just prior Lpath’s reverse merger with the public company Neighborhood Connections Inc.; the 58-month warrants are exercisable at $1.50 per share; Roaring Fork Capital SBIC LP led the financing (12/8) MicroIslet Inc. (AMEX:MII) Private placement of stock and warrants 2.285S and 1.14W $3.4 The shares were sold at about $1.50 each; the fiveyear warrants are exercisable at $1.65 per share (12/27) MacroChem Corp. (OTC BB: MCHM) Private placement of convertible notes and warrants N/A and 100W $2.5 The 10% notes are convertible into 100M shares of common stock; the six-year warrants are exercisable at $0.03 per share (12/28) Neuren Private Pharmaceuticals placement of Ltd. (Australia; stock ASX:NEU) 12S A$6.36 ($4.75) The shares were sold at $0.53 each in a placement co-managed by Taylor Collision Ltd. and Patersons Securities Ltd. (12/2) Oncolytics Private Biotech Inc. placement of (Canada; TSE:ONC) stock and warrants 3.2S and 1.6W C$16.5 ($14.3) Units were sold at C$5. 1 5 each, consisting of one share and half a warrant; each whole warrant is exercisable for three years at C$6.15 per share (12/13) OSI Private Pharmaceuticals placement of Inc. (OSIP) convertible notes N/A $100 The 2% notes mature in 2025 and are convertible into stock at an initial price of $29.43 per share, a premium of 25% (12/15) ProMetic Life Sciences Inc. (Canada; TSE:PLI.SV) Private placement of convertible notes N/A $8.9 The notes are convertible into common stock at C$0.32 per share; the notes are repayable in cash and/or stock (12/21) SemBioSys Genetics Inc. (Canada; TSE:SBS) Private placement of stock and warrants 3.86S and 1.932W C$15.6 ($13.4) Units consisting of one share and half a warrant were placed at C$4 apiece; each whole warrant is exercisable for 30 months at C$5.50 per share; underwriters, led by Orion Securities Inc. and including Versant Partners Inc., Canaccord Capital Corp. and Westwind Partners Inc., exercised their option on an additional 1.3M units in the deal (12/6) Stressgen Biotechnologies Corp. (Canada; TSE:SSB) Private placement of stock and warrants 2.685S and 0.9W C$0.94 ($0.81) Canaccord Capital Corp. exercised its overallotment option to purchase additional units from a C$2.68M financing completed in November; the two-year warrants are exercisable at C$0.50 per share (12/14) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 89 2005 Miscellaneous Financings Of Public Biotech Companies (Continued) Company (Country; Symbol) Type Of Financing Number Amount Of Shares, Units Raised (M) Or Warrants (M) Vernalis plc (UK; VNLS) Private placement of stock 24.28S £15.3 ($26.6) Investors; Placement Agents; Details (Date) Proceeds from the placement were received by former Cita NeuroPharmaceuticals Inc. shareholders as part of Vernalis’ acquisition of Cita; Piper Jaffray was placement agent (12/14) Notes: This chart does not include real estate or manufacturing plant financings, or debt deals done to replace existing debt. Currency conversions are based on exchange rates at the time of the deal. N/A = Not applicable; ND = Not disclosed. S = Shares; U = Units; W = Warrants # Unless otherwise indicated, shares are traded on the Nasdaq exchange. AIM = Alternative Investment Market; AMEX = American Stock Exchange; ASX = Australian Stock Exchange; CDNX = Canadian Venture Exchange; CSE = Copenhagen Stock Exchange; FSE = Frankfurt Stock Exchange; HSE = Helsinki Stock Exchange; LSE = London Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; PK = Pink Sheets; SPE = Spanish Stock Exchange; SSE = Stockholm Stock Exchange; SWX = Swiss Stock Exchange; TEL = Tel Aviv Stock Exchange; TSE = Toronto Stock Exchange. 90 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms Company Location Date Amt. (M) Details Adenosine Therapeutics LLC Charlottesville, Va. 1/25/05 $3.5 Details on the financing were not disclosed Alexza Molecular Delivery Corp. Palo Alto, Calif. 1/6/05 $52 Alloy Ventures and Delphi Ventures co-led the Series D financing, which included Abingworth Bioventures, MDS Capital, Pacific Rim Ventures, T. Rowe Price, WestRiver Capital, Alejandro Zaffaroni, Frazier Healthcare, Versant Ventures, 5AM Ventures, Burrill & Co., CMEA Ventures, New Enterprise Associates and Zesiger Capital Group Apoxis SA Lausanne, Switzerland 1/25/05 €15 ($19.5) Participating in the second-round financing were Novo Nordisk, Banexi Ventures Partners, HealthCap and private investors Biolipox AB Stockholm, Sweden 1/10/05 $41 The Series C round was led by Scandinavian Life Science Venture and included existing investors HealthCap, Apax Partners, Sofinnova Partners, Auriga Partners and Crédit Lyonnais Private Equity BioWisdom Ltd. Cambridge, UK 1/31/05 £2.3 ($4.3) New investors Finsbury Life Sciences Investment Trust and NIF Ventures Ltd. were joined by returning investors, including Merlin Biosciences and MB Venture Capital, in the financing round Chelsea Therapeutics Inc. Charlotte, N.C. 1/1 1/05 $14.5 The company sold Series A convertible preferred stock in the round; Paramount BioCapital Inc. was placement agent Compound Therapeutics Inc. Waltham, Mass. 1/18/05 $15.5 The company raised $15.5M in an expansion of its Series A financing; it raised $12M in May 2003; investors included Atlas Venture, Flagship Ventures and Polaris Venture Partners DanioLabs Ltd. Cambridge, UK 1/17/05 £3.2 ($6) Cambridge Gateway Fund led the first-round financing, which also included Merifin, NVM and existing and new angel investors Efficas Inc. Boulder, Colo. 1/4/05 $3 The Series A-3 round was led by the Bay Area Equity Fund and included Boston Life Science Venture Corp.; total investment in the company is about $8.5M JANUARY BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 91 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Elbion AG Dresden, Germany 1/10/05 €25 ($32.4) The Degussa AG spinout completed a first-round financing co-led by 3i, Burrill & Co. and DVC Deutsche Venture Capital; other investors were AGF Private Equity, Quintiles PharmaBio Development, BayTech Venture Capital and Marubeni Corp. Immutep SA Orsay, France 1/10/05 €2.5 ($3.3) Innoven Partenaires led the second-round financing, which included an investment from Equitis’ H2I fund Nereus San Diego Pharmaceuticals Inc. 1/4/05 $24.3 New investors HBM BioVentures Ltd. and HBM BioCapital LP led the Series D preferred round, expected to be the first tranche of a $42.6M deal; other investors were Advent International, InterWest Partners, Genavent Partners, Red Abbey Venture Partners, Alta Partners, Forward Ventures, GIMV, Novartis Bioventure Fund, Pacific Venture Group, FirstBio and Lotus BioScience Ventures Neuro3d Mulhouse, France 1/3/05 €34.5 ($41.3) Gilde Investment Management’s Biotech fund and AXA Private Equity led the Series C financing, which also included Healthcare Private Equity LP, GIMV, HealthCap, Techno Venture Management Partners, Sofinnova Partners and APAX Partners OctoPlus Technologies BV Leiden, the Netherlands 1/20/05 $23.85 The second-round financing was led by Life Sciences Partners II BV and S.R. One Ltd., and included Innoven Partenaires, Fortis Private Equity and SurModics Inc.; Fortis Bank was placement agent OpGen Inc. Madison, Wis. 1/24/05 $5 The company completed a Series B round of financing; investors included Mason Wells Biomedical Fund, Stonehenge Capital, The State of Wisconsin Investment Board and The Wisconsin Alumni Research Foundation Paradigm Therapeutics Ltd. Cambridge, UK 1/7/05 £5.5 ($10.3) Bio*1Capital, Merlin Biosciences and Avlar BioVentures invested additional money in the company following its acquisition of Amedis Pharmaceuticals Ltd. Pennsylvania companies Philadelphia 1/25/05 $3.5 BioAdvance is providing a total of $3.5M in seed capital to the following companies: Avid Radiopharmaceuticals, Marillion Pharmaceuticals, InfraScan, Galleon Pharmaceuticals, Jerin Discovery, Melior Discovery and SansRosa Pharmaceuticals 92 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details PolyMedix Inc. Philadelphia 1/5/05 $6 The company had two closings in a Series B financing round; details were not disclosed Predix Woburn, Mass. Pharmaceuticals Inc. 1/25/05 $43 The Series C financing round was led by Forward Ventures, Boston Millennia Partners and CMEA Ventures and included new investors Novel Bioventures, Yamanouchi Venture Capital, Yasuda and JAFCO Ventures and previous investors OrbiMed Advisors LLC, S.R. One, Yozma Group, International Life Science Partners and PA Consulting Protalix Biotherapeutics Ltd. Karmiel, Israel 1/12/05 $1.3 The funding was provided by investment fund Pontifax, which has an option to invest another $1M Spaltudaq Corp. Seattle 1/24/05 ND The company, started by Accelerator Corp., completed a Series A financing that included MPM Capital, ARCH Venture Partners, Amgen Ventures, OVP Venture Partners, Versant Ventures and Alexandria Real Estate Equities VirtualScopics LLC Rochester, N.Y. 1/6/05 $1.4 An affiliate of Loeb Partners Corp. exercised all the warrants it received in its initial investment in VirtualScopics Vitae Fort Washington, Pa. Pharmaceuticals (formerly Concurrent Pharmaceuticals) 1/4/05 $34 New investors Atlas Venture and Wellcome Trust joined existing investors Prospect Venture Partners, Venrock Associates and New Enterprise Associates in the financing round Zealand Glostrup, Denmark Pharmaceuticals A/S 1/7/05 €13.3 ($17.3) BankInvest led the financing round, which also included LD Pension, Dansk Erhvervsinvestering and Vaekstfonden Abeille Princeton, N.J. Pharmaceuticals Inc. 2/22/05 $1.5 Accredited investors participated in the Series A financing round; details were not disclosed Advanced Cell Technologies Inc. Worcester, Mass. 2/1/05 $8 The company sold Series A preferred stock and warrants just prior to its reverse merger with A.C.T. Holdings Inc. (OTC BB:ACTH); the securities converted into ACTH stock and warrants Archimedes Pharma Ltd. London 2/9/05 $40 Warburg Pincus invested $40M in the new company, which acquired the nasal drug delivery assets of West Pharmaceutical Services Inc. 93 FEBRUARY BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Biosystems International Evry, France 2/4/05 €3 ($3.8) Two funds managed by Société Générale Asset Management invested in the company’s first financing round Cavis Microcaps GmbH Mainz, Germany 2/3/05 €5 ($6.4) Inventages Venture Capital Investment Inc. and BASF Venture Capital invested in the Series A financing round FibroGen Inc. South San Francisco 2/16/05 $100 Adage Capital Management led the financing; also participating were Apothecary Capital, Brookside Capital Partners, Corriente Biotechnology Partners, Duquesne Capital Management, Goldman Sachs, Janus Capital Group, Merlin BioMed Group, Och-Ziff Capital Management, The Rosewood Corp., Sigma Capital Management, T. Rowe Price, Yamanouchi Pharmaceutical Co. Ltd., SMBC Capital and Bio Fund Management FivePrime Therapeutics Inc. South San Francisco 2/8/05 $45 Domain Associates LLC led the financing round that also included HealthCap, the JP Morgan Bay Area Equity Fund, Kleiner Perkins Caufield and Byers, Versant Ventures, Texas Pacific Group, Advanced Technology Ventures, The Wellcome Trust, Diamond Capital Co. Ltd. and Singapore BioInnovations Pte. Ltd.; Three Crowns Capital served as adviser to the company Jerini AG Berlin 2/14/05 €15.5 ($20.2) The financing round was co-lead by NGN Capital, Life Sciences Partners and The Bioscience Investment Trust plc; also participating were existing investors Healthcap, TVM, 3i Group Investments LP and funds managed by IBB Beteiligungsgesellschaft Kiadis BV Groningen, the Netherlands 2/3/05 €4 ($5.2) The Series B financing round was led by Life Sciences Partners and included existing investor Prelude Trust plc and new investor NV NOM Medisyn Technologies Inc. Minneapolis 2/17/05 $1.5 MTI Investors LLC led the bridge financing round; current investors Sherpa Trek I LP, StarTec Investments, Andcor Cos. Inc. and Portage Capital took part in the offer of convertible notes and warrants M-phasys GmbH Tubigen, Germany 2/8/05 ND Investors in the Series C financing included KfW Bankengruppe, Grazia Equity, Gradus Ventures, Heidelberg Innovation and TechnoStart Ventures 2/21/05 €30 ($39.7) HBM Partners AG was lead investor in the round; existing investors 3i Group, Apax Partners and Atlas Venture also participated Newron Milan, Italy Pharmaceuticals SpA 94 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Opsona Therapeutics Ltd. Dublin, Ireland 2/24/05 €6.25 ($8.2) Inventages Venture Capital and Seroba BioVentures led the Series A financing, which also included Genentech Inc. and Enterprise Ireland Perlegen Sciences Inc. Mountain View, Calif. 2/28/05 $74 The Series D financing was led by CSK Venture Capital; new investors included Brookside Capital, Mizuho Securities, Glynn Capital Management and Cape Securities; previous investors participating included Alejandro Zaffaroni, Maverick Capital, Lombard Odier Darier Hentsch &Cie, Zesiger Capital, Sano Ventures, BSI SA, MPM BioEquities, SB Life Sciences, Unilever Ventures, Biofrontier Partners, Private Life Biomed, CMEA Ventures and Affymetrix Inc. Sciona Inc. Boulder, Colo. 2/28/05 $8.2 Burrill & Co. led the second closing of the thirdround financing, which also included Prelude Trust, BASF Venture Capital GmbH and Bioventures Inc. Speedel Group Basel, Switzerland 2/22/05 CHF47.8 ($41) Speedel completed an equity round of financing; the majority of the funding came from current shareholders Stirling Medical Solutions Ltd. Stirling, Scotland 2/28/05 £97.5 ($186.4) Inverness Medical Innovations Inc. set up Stirling and committed to invest £67.5M over three years; ITI Life Sciences, a public entitiy, is providing £30M to the diagnostics company, a subsidiary of IMI The Genetics Co. Inc. Schlieren, Switzerland 2/15/05 CHF17 ($14.3) Nextech Venture, the Novartis Venture Fund and Varuma AG led the Series C round; they and other investors have an option to invest another CHF8M to bring the round to CHF25M Voyager Pharmaceutical Corp. Raleigh, N.C. 2/14/05 $16 Non-institutional investors participated in the financing, with more than 90% of it from current shareholders 2/21/05 €13 ($17.2) Zealand completed a second closing of a Series C round; the first closing of €13M occurred in January; investors in the second closing included CDC Enterprises Innovation, AGF Private Equity and Life Sciences Partners 3/30/05 $22 All major existing shareholders in the company participated in the financing, which also included new investors 95 Zealand Glostrup, Denmark Pharmaceuticals A/S MARCH Agennix Inc. Houston BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Date Amount (M) Details Alantos Cambridge, Mass. Pharmaceuticals Holding Inc. 3/10/05 $20 Participating in the Series B financing were existing investors Oxford Bioscience Partners, SV Life Sciences, Earlybird, ABN AMRO, Heidelberg Innovation and Ventech Arginox Menlo Park, Calif. Pharmaceuticals 3/1/05 $25 The Series C round was led by existing investor Topspin Partners; Perseus Soros Biopharmaceutical Fund also participated B-Bridge International Inc. Sunnyvale, Calif. 3/29/05 $4.2 Bio-sight Capital Co. Ltd. led the financing, which also included Hokkaido Venture Capital Inc., Marubeni Corp. and existing investors Borean Pharma A/S Aarhus, Denmark 3/23/05 €4 ($5.2) The Series A financing was led by Aravis Venture and included existing investors BankInvest, Novi and Incuba Cleveland BioLabs Cleveland 3/25/05 $5.9 Sunrise Equity Partners LP led a group of private and institutional investors in the financing round Evolva Biotech SA Allschwil, Switzerland 3/22/05 CHF3 ($2.5) New investor Andhra Pradesh Industrial Development Corp. Venture Capital led the second close of the company’s Series A financing; it raised CHF18.5M in the first close in August 2004 Fibrex Medical Inc. Wilmington, Del., and Vienna, Austria 3/15/05 $10 Global Life Science Ventures and Atlas Venture led the Series A financing, which included EMBL Ventures and Mulligan BioCapital GeneExcel Inc. Houston 3/15/05 $1 ITX International Holdings Inc., which licensed certain rights from GeneExcel, invested $700,000 in the Series A round; Alkek Ventures and some private investors also participated ImaRx Therapeutics Inc. Tucson, Ariz. 3/10/05 $7 First Montauk Securities Corp. was placement agent for the financing KaloBios Palo Alto, Calif. Pharmaceuticals Inc. 3/16/05 $20 The Series B financing round was led by MPM Capital and GBS Venture Partners and included Lotus BioScience Ventures and existing investors Sofinnova Ventures, Alloy Ventures, 5AM Ventures and Singapore BioInnovations Pte. Ltd. Mitra Medical AB 3/30/05 SEK30 ($4.2) Inter Ikea and Industrifonden invested in the financing round 96 Location Lund, Sweden BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Nautilus Biotech Paris 3/1/05 €7.25 ($9.6) Auriga Partners led the financing round; investors in the company include Matignon Technologies, Edmond Rothschild Investment Partners, FCJE, Pre-IPO Invest, 123 Venture and Creabilis Biotech Performance Plants Inc. Kingston, Ontario 3/23/05 C$1.5 ($1.2) Participating in the financing round were existing investors Golden Opportunities Fund, Dynex Capital Partners and Venture Link Funds PharmAthene Inc. Annapolis, Md. 3/10/05 ND Simultaneous with its acqusition of Protexia technology from Nexia Biotechnologies Inc., the company completed a Series C financing; investors included Teachers’ Private Capital, Canadian Medical Discoveries Fund Inc., MDS Life Sciences Technology Fund US LP, MPM Capital, Bear Stearns Health Innoventures and HealthCare Ventures Rosetta Genomics Ltd. Rehovot, Israel 3/22/05 $4 Kadima High Tech led the Series C round, which included Teva Pharmaceutical Industries Ltd., GlenRock Israel and a number of individual investors Sequoia Gaithersburg, Md. Pharmaceuticals Inc. 3/20/05 $22 The Series B financing was led by Health Care Ventures and included Sofinnova Partners, Aberdare Ventures and The Wellcome Trust Sirtris Waltham, Mass. Pharmaceuticals Inc. 3/7/05 $27 The Series B round was led by new investor Three Arch Partners and co-led by Cargill Ventures, and included Novartis Bioventures Fund, Polaris Venture Partners, Techno Venture Management, Cardinal Partners, Skyline Ventures and The Wellcome Trust TolerRx Inc. Cambridge, Mass. 3/29/05 $31 Bear Stearns Health Innoventures led the Series D financing, which included all existing investors as well as NIF Ventures and individuals TopoTarget A/S Copenhagen, Denmark 3/16/05 €15 ($19.8) Investors in the Series C financing included BankInvest, HealthCap and Deutsche Venture Capital TorreyPines Therapeutics Inc. San Diego 3/16/05 $34.8 The company changed its name from Neurogenetics Inc.; Johnson & Johnson Development Corp. and Alta BioPharma Partners led the Series C round; other investors included NIF Ventures, Sorrento Ventures, GIMV, Alta Partners, Advent International, Novartis Venture Fund and S.R. One BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 97 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Actimis San Diego Pharmaceuticals Inc. 4/28/05 $6 Sanderling Ventures led the Series A financing, which also included Mitsui & Co. Venture Partners; Actimis was spun out of Bayer HealthCare AG Affectis Munich, Germany Pharmaceuticals AG 4/13/05 €4 ($5.17) The Series B financing round was led by EMBL Ventures; additional new investors Adamant, KfW and Sunrise Water Ltd. joined existing investors LSP, BayernKapital and the Max Planck Society Ambrx Inc. 4/8/05 $23.4 The second-round financing included new investors Maverick Capital, CMEA Ventures, Twilight Venture Partners and Alexandria Real Estate Equities and existing investors Tavistock Life Sciences, 5AM Ventures, Versant Ventures and Aravis Ventures Anthera San Francisco Pharmaceuticals Inc. 4/21/05 ND The new company completed a Series A financing CellCentric Ltd. Cambridge, UK 4/7/05 £0.25 ($0.47) The Rainbow Seed Fund invested in the financing that adds on to the company’s initial round DNage BV Rotterdam, the Netherlands 4/13/05 €1.5 ($2) Inventages Venture Capital and Life Sciences Partners invested in the seed round of the firm, which was spun out of Erasmus Medical Center GeneOhm Sciences Inc. San Diego 4/1/05 ND Partners HealthCare System Inc. invested in the company in a follow-on Series C financing Gentris Corp. Morrisville, N.C. 4/27/05 $5 Mitsui & Co. (U.S.A.) Inc. provided funding for the Series C financing round Hamilton Washington Pharmaceuticals Inc. 4/22/05 $1 1.1 Founding investors Vivo Ventures LLC and CNF Investments LLC were joined by Index Ventures in the Series A financing Ikaria Inc. Seattle 4/26/05 ND The new company received investments from ARCH Venture Partners, Venrock Associates, 5AM Ventures, Aravis Ventures and the Washington Research Foundation Ipsat Therapies Helsinki, Finland 4/4/05 €7 ($9) The financing round was led by Bio Fund Management Oy, with Finnish Industry Investment Ltd., the Varma Mutual Pension Insurance Co. and Sitra also investing APRIL 98 San Diego BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Merrimack Cambridge, Mass. Pharmaceuticals Inc. 4/20/05 $37.3 The financing comprises $28.3M of Series D stock and a $9M venture loan; existing investors Sorenson Development Inc., Unilever Technology Ventures Fund BV and Wharton Biotechnology Partners were joined by WT Investment Advisors; the loan was provided by Hercules Technology Growth Capital Molecular Cambridge, Mass. Insight Pharmaceuticals Inc. 4/21/05 $28 New investors Siemens Venture Capital GmbH Corp., Tudor Investment Corp., MedCap Management & Research LLC and Emigrant Capital Corp. joined existing investors in the Series C financing round; SG Cowen & Co. was placement agent NanoString Technologies Inc. Seattle 4/27/05 $3.8 Series A investors that invested $4.3M in August 2004 increased the round to $8.1M by exercising warrants in full; the investors were Draper Fisher Jurvetson and OVP Venture Partners Oxford Genome Sciences Ltd. Oxford, UK 4/4/05 ND The South East Growth Fund led the secondround financing, and Oxford Capital Partners joined as a new investor Receptor Biologix Inc. South San Francisco 4/28/05 $33.6 Skyline Ventures led the Series A financing, which also included Domain Associates, Essex Woodlands Health Ventures, MedImmune Ventures, Takeda Research Investment Inc. and Northwest Technology Ventures Syntarga BV Nijmegen, the Netherlands 4/15/05 ND Aglaia Oncology Fund led the Series A financing, with BioPartner Start-up Ventures as co-investor Talecris Biotherapeutics Inc. Research Triangle Park, N.C. 4/1/05 ND The company was formed from the purchase of Bayer HealthCare LLC’s plasma business; Cerberus Capital Management LP and Ampersand Ventures provided financing for Talecris Ventaira Columbus, Ohio Pharmaceuticals 4/4/05 $13.5 TL Ventures led the Series C round, which included Battelle Ventures, Battelle, Safeguard Scientific, PA Early Stage Partners, Fletcher Spaght Ventures LP, Reservoir Venture Partners and James Richardson & Sons Ltd. Xceleron Ltd. 4/28/05 £2 ($3.8) Close Venture Management led the financing round with a £1.5M investment, while Foursome Investments provided £0.5M Heslington, UK BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 99 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details AC Immune Ecublens, Switzerland 5/1 1/05 CHF21 ($17.2) New investors contributed two-thirds of the funds in the Series B financing round Ambit Biosciences Corp. San Diego 5/12/05 $10 Ambit completed the second close of its Series C financing, which now totals $31M; it raised $21M in August 2004; Roche Venture Fund led the round, which included Perseus-Soros Biopharmaceutical Fund, Forward Ventures, GIMV, Avalon Ventures and new investors Canadian Medical Discoveries Fund Inc. and Genechem Anacor Palo Alto, Calif. Pharmaceuticals Inc. 5/1 1/05 $25 The Series C financing was co-led by Care Capital and Venrock Associates; other new investors included Red Abbey Venture Partners and individuals associated with Anacor; existing investors Aberdare Ventures and Rho Ventures also participated Androclus Therapeutics San Diego 5/16/05 ND E. de Rothschild Investment Partners and Matignon Technologies led the company’s first institutional financing round Assay Designs Inc. Ann Arbor, Mich. 5/12/05 $5 Ampersand Ventures was the sole investor in the the company’s Series A financing round Avidia Inc. Mountain View, Calif. 5/4/05 $28.5 Morgenthaler Ventures led the Series B financing, which also included TPG Ventures, MedImmune Ventures, Amgen Ventures and existing Series A shareholders Alloy Ventures, Maxygen Inc., Willem Stemmer and several individuals Bayhill Therapeutics Inc. Palo Alto, Calif. 5/4/05 $35.4 De Novo Ventures and Lilly Ventures led the Series B financing, and were joined by CMEA Ventures, Latterell Venture Partners, Morgenthaler Ventures, U.S. Venture Partners, the Vertical Group, A.M. Pappas Life Science Ventures, Boston Life Science Venture Corp., Grand Cathay Venture Capital Co. Ltd., Montreux Equity Partners, PACLINK Bio Management Corp., Prudence Venture Investment Corp. and Quintiles’ PharmaBio Development 5/18/05 $1 1.8 The follow-on Series C investment brings the Series C investment to $37.5M; $25.7M was raised in November 2004; investors in this closing included Noro-Moseley, PTV Sciences, Axiom Ventures and HSS Ventures MAY BioMimetic Franklin, Tenn. Pharmaceuticals Inc. 100 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Biopheresis Technologies Inc. Cary, N.C. 5/12/05 €6.5 ($8.2) Participating in the Series A round were European investors Scandinavian Life Science Venture and First Ventury Celator Princeton, N.J. Pharmaceuticals Inc. 5/3/05 $40 New investors Domain Associates, Quaker BioVentures and TL Ventures joined existing investors Ventures West, GrowthWorks Capital and the Business Development Bank of Canada in the financing round Cellerant Therapeutics Inc. Palo Alto, Calif. 5/1 1/05 $16 Novel Bioventures led the Series B financing, which included George Rathmann, CX Venture Group, Allen & Co. and MPM Capital Conforma Therapeutics Corp. San Diego 5/2/05 $1 1 Conforma added $1 1M to a Series C round from September 2003, bringing the total to $41.5M; returning investors included Domain Associates, Forward Ventures, Inglewood Ventures, Lilly BioVentures, Novo A/S, ProQuest Investments, RBC Capital Partners, RiverVest Venture Partners and S.R. One Ltd. Cylene San Diego Pharmaceuticals Inc. 5/25/05 $26.3 The Series B financing was led by Coastview Capital; other new investors included BioVentures Investors, Mitsui & Co. Venture Partners, Morningside Venture Investments, TDL Investors, William Harris Investors, Lakeview Capital and the Viterbi Group; all existing shareholders also participated Cytochroma Inc. Markham, Ontario 5/5/05 C$15 ($12) The company received the first tranche of a C$15M financing, which was led by VenGrowth Private Equity Partners Inc. and included all current investors Elbion AG Dresden, Germany 5/24/05 €10 ($12.2) Elbion added €10M to its Series A funding round, which now totals €35M; it raised €25M in January; additional investors include Techno Venture Management, Temasek Holdings and Mitsubishi Corp. Evogene Ltd. Rehovot, Israel 5/31/05 $1.75 The company raised the money from new and existing investors in Israel, France and North America FASgen Inc. Baltimore 5/13/05 $2 A private investor provided the funding to support development of the company’s tuberculosis drug candidate BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 101 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Date Amount (M) Details Gemin X Montreal Biotechnologies Inc. 5/19/05 $65.2 The Series D funding consists of a $50M equity investment and up to $15.2M in a loan facility; the H.I.G. and Sanderling groups of funds led the financing, which included Merlin BioMed Group, Pinnacle Biotech Ventures Fund and all current investors; Investissement Quebec’s Biolevier Program provided the loan Genomatix Corp. Roanoke, Va. 5/17/05 $0.5 NewVa Capital Partners LP provided the funding for the the company’s Series B financing HTG Inc. Tucson, Ariz. 5/4/05 $3.4 Investing in the Series B round were Solstice Capital, Valley Ventures, Emerging Technology Partners, Deimos Ventures, Village Ventures, members of the Tucson Desert Angels and HTG founder Bruce Seligmann Intercept New York Pharmaceuticals Inc. 5/4/05 $1.25 Rodman & Renshaw led the convertible debt financing, which also included investments from individuals and institutions LifeCycle Pharma A/S 5/17/05 €15 ($19) Alta Partners led the Series C financing round, which included DG Lux Multimanager I Sicav Lacuna Apo BioTech Subfund and existing investors H. Lundbeck A/S, Novo A/S and Nordic Biotech Montigen Salt Lake City Pharmaceuticals Inc. 5/13/05 $5.2 Details on the Series A financing were not disclosed NsGene A/S Ballerup, Denmark 5/2/05 DKK30 ($5.2) NeuroSearch A/S and other existing shareholders invested in the financing round; NeuroSearch’s stake increased to 25.3% from 25% Oxagen Ltd. Abingdon, UK 5/23/05 $59.8 MPM Capital led the Series B financing round, which included new investors Bessemer Venture Partners, IBT and Red Abbey and existing investors SV Life Sciences, Advent Ventures, 3i, Abingworth and The Wellcome Trust Phenomix Corp. San Diego 5/24/05 $40 New investors JPMorgan Partners and Delphi Ventures co-led the Series B financing, which included new investor Baker Brothers Investments and existing investors Alta Partners, Sofinnova Ventures, Bay City Capital, CMEA Ventures, GBS Venture Partners and Novartis BioVenture Fund 102 Location Horsholm, Denmark BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Prolysis Ltd. Oxford, UK 5/24/05 $9.9 The Series B financing round was led by existing institutional investors, and was joined by Fujisawa Investments for Entrepreneurs LP and Fujisawa Investments for Entrepreneurs II LP Spherics Inc. Lincoln, R.I. 5/12/05 $26.4 Advent International led the Series C financing, which included new investors MVM Life Sciences, Oakwood Medical Investors, AM Pappas, Mitsubishi and Vectis Life Sciences Fund, as well as Series A and B investors Zero Stage Capital, CB Health Ventures, POD Holding and Eastman Ventures Tranzyme Pharma Research Triangle Park, N.C. 5/13/05 $32 H.I.G. Ventures; Thomas, McNerney & Partners; and Quaker BioVentures led the Series C financing, which included existing investors Business Development Bank of Canada, Desjardins Venture Capital, Pacific Rim Ventures and The Solidarity Fund Wilex AG Munich, Germany 5/10/05 €30 ($38.4) Merlin Biosciences led the Series C round, which included new investors Karolinska Investment Fund, Quest for Growth, Quintiles’ PharmaBio Development and existing investors Apax Partners, TVM Techno Venture Management, Earlybird Venture Capital and others Zelos Therapeutics Inc. Waltham, Mass. 5/18/05 $42.5 Alta Partners led the Series B financing, which included other new investors Prospect Venture Partners, Frazier Healthcare Ventures, SR One and the Ontario Teacher’s Pension Plan and existing investors VenGrowth Private Equity Partners Inc., Genesys Capital Partners Inc., Seaflower Ventures and the Business Development Bank of Canada; Ferghana Securities managed the financing AgraQuest Inc. Davis, Calif. 6/7/05 $14.35 The financing round was co-led by Otter Capital LLC and new investors Texas Pacific Group and Halcyon Capital; also participating were existing investors SAM Sustainability Private Equity LP, Sustainable Performance Group NV, Swiss Re Investors, Berndt Trusts, JSS Management, Vivo Ventures and Boldcap Ventures AmpliMed Corp. Tucson, Ariz. 6/21/05 $5 Biotech Insight Ventures led the Series B financing round, which included previous investors InvestBio Ventures, Valley Ventures and Solstice Capital 103 JUNE BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Borean Pharma A/S Aarhus, Denmark 6/15/05 €1.5 ($1.8) New investor ABN Amro invested €1.5M in a second closing in the Series A round; Borean raised €4M in the first closing in March Codon Devices Cambridge, Mass. 6/1/05 $13 Founding investor Flagship Ventures led the Series A financing round, which also included Alloy Ventures, Kleiner Perkins and Vinod Khosla Diabetica Ltd. Coleraine, Northern Ireland 6/15/05 ND UUTech Ltd., the technology transfer arm of the University of Ulster, and Seroba BioVentures provided funding for the university spin-off DrugAbuse Sciences SAS Lyon, France 6/27/05 €5 ($6) Existing shareholders including 3i, Alpinvest, Canaan Partners, CDC Innovation, Nomura Phase IV Ventures, Philippe Pouletty and CDC participated in the convertible bridge loan financing; a new management team was named and a relocation to Paris was planned Endotis Pharma Paris 6/20/05 €4 ($4.9) Sofinnova Partners provided the funding for the company’s Series A financing round Exiqon A/S Copenhagen, Denmark 6/2/05 $20 Teknoinvest led the Series C financing round, which also included Scandinavian Life Science Venture, Nobel Group, LD Pensions, BioFund and Danske Bank GNI Ltd. Tokyo 6/20/05 $13 GNI raised the money concurrent with its merger with Shanghai Genomics Inc.; the financing was led by Nomura, Healthcare Partners and other U.S. and Japanese private equity firms iCeutica Inc. Philadelphia 6/20/05 ND Phoenix IP Ventures led the company’s Series A round of financing Inimex Vancouver, British Pharmaceuticals Columbia Inc. 6/15/05 C$4 ($3.2) Completion of 2005 R&D milestones triggered release of another C$4M in funds from Series A investors, which invested C$6M in the company in July 2004 Innovive New York Pharmaceuticals Inc. 6/29/05 $2.25 The money was raised in a convertible note financing; Paramount BioCapital Inc. was placement agent 104 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amt. (M) Details Jazz Palo Alto, Calif. Pharmaceuticals Inc. 6/27/05 $80 Lehman Brothers Principal Investments led the debt financing Series C round, which closed along with Jazz’s acquisition of Orphan Medical Inc.; other investors included General Electric Pension Trust, Deep Cove Mezzanine LLC and entities related to Oak Hill Advisors and Oak Hill Investment Management Morria BioLondon pharmaceuticals plc 6/8/05 £2.1 ($3.8) Financial consultants Charles Street Securities led the Series A financing round, which followed a £0.2M private bridge financing Osiris Therapeutics Inc. Baltimore 6/8/05 $50 The company sold equity and convertible debt in the financing round; Friedli Corporate Finance Inc. arranged the financing Santaris Pharma A/S Copenhagen, Denmark 6/29/05 €4.4 ($5.3) The financing was the first closing of what was expected to be a €20M second round that closed later in 2005; investors were BankInvest, Novo, LD Pension, InnovationsKapital, Dansk Kapitalanaeg and Dansk Erhvervsinvestering Somaxon San Diego Pharmaceuticals Inc. 6/6/05 $65 MPM Capital Partners led the Series C round, which included additional new investor Prospect Ventures; existing investors Domain Associates LLC, BA Venture Partners, Montreux Equity Partners and CDIB BioScience Ventures also participated Therion Biologics Corp. 6/17/05 $30 The financing round was led by Hans-Werner Hector, and included Loeb Investors, SRK Management Co. and Cheng Xin Venture Capital Group Tioga San Diego Pharmaceuticals 6/15/05 ND Forward Ventures provided Series A financing for Tioga, which was formed to develop asimadoline, a product acquired from Merck KGaA TriMed Research Inc. 6/20/05 €5 ($6) Inventages Venture Capital Investments Inc. and Seroba Bioventures participated in the Series A financing round 6/9/05 $98 The Series A financing included $78M in equity and $20M in product-specific royalty financing from Paul Royalty Fund; the equity investment was led by Domain Associates and Prospect Venture Partners and included Paul Royalty Fund, MPM Capital, Montreux Equity Partners, Athenian Venture Partners, Windamere Venture Partners and private investors Cambridge, Mass. Omaha, Neb. Verus San Diego Pharmaceuticals Inc. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 105 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amt. (M) Details Ziopharm Inc. Charleston, Mass. 6/6/05 $18.1 Paramount BioCapital Inc. was the lead placement agent in the Series A convertible preferred stock sale Affymax Inc. Palo Alto, Calif. 7/18/05 $60 The Series D financing was co-led by new investor JAFCO Co. Ltd. and existing investor Bear Stearns Health Innoventures; also participating were new investors Bessemer Venture Partners, Merlin BioMed Group and Diamond Capital Co. and existing investors Apax Partners, MPM Capital and Sprout Group; Montgomery & Co. LLC was placement agent Altea Therapeutics Corp. Atlanta 7/28/05 $30 The Series C financing was led by Aperture Venture Partners and included Series B investors Domain, Venrock and vSpring Capital, as well as KBC, Quilvest, CX Ventures and Rockport Ventures APT Tucson, Ariz. Pharmaceuticals Inc. 7/21/05 $6 The Series A financing round was led by new investor Charter Life Sciences and existing investor Research Corporation Technologies BrainCells Inc. San Diego 7/14/05 $8 Technology Partners and seed investors Oxford Bioscience Partners and Bay City Capital led the Series A round, and were joined by A. M. Pappas & Associates and Neuro Ventures; they will invest another $9.7M if certain milestones are met 4SC AG Martinsried, Germany 7/12/05 €6.5 ($7.9) The company’s Series D financing round had two closings; investors were KfW SME Bank, Bayern Kapital, Deutsche Venture Capital Gesellschaft, 3i, BioM and Mulligan BioCapital Ilypsa Inc. Santa Clara, Calif. 7/19/05 $36 The Series B financing round was co-led by new investors US Venture Partners, Johnson & Johnson Development Corp. and Delphi Ventures; also participating were new investors CMEA Ventures and Mediphase Venture Partners and existing investors Sprout Group and 5AM Ventures Immune Control Inc. Conshohocken, Pa. 7/14/05 $1 1.3 Series A financing for the Drexel University spinout was provided by BioAdvance Ventures, Domain Associates, NewSpring Capital and Anthem Capital JULY 106 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details NovaThera Ltd. Cambridge, UK 7/12/05 £2.75 ($4.8) The company completed a Series A funding round of up to £2.75M Panacea Gaithersburg, Md. Pharmaceuticals Inc. 7/7/05 $7 Investors in the Series C financing included Mitsubishi Corp. Life Sciences Venture, Olympus, JSR, Shin-Etsu Chemical, Fuji Photo Film, Dai Nippon Printing and Tokio Marine & Nichido Fire Insurance; Cosmos Alliance assisted in the deal Pepscan Systems BV Lelystad, the Netherlands 7/8/05 €5 ($6) Convertible notes were sold in the company’s first financing round to Dutch investors PPM Oost NV, Lupus Ventures BV, Wageningen Business Generator BV, Technofund Flevoland BV and private and existing investors Peptimmune Inc. Cambridge, Mass. 7/15/05 $20.4 Participating in the Series C round were existing investors New Enterprise Associates, MPM Capital, Prism Venture Partners, Vanguard Ventures, Hunt Ventures LP and Boston Medical Investors Inc. and new investors Itochu Corp. and Silicon Valley Bank Capital Primera Biosystems Inc. Providence, R.I. 7/1 1/05 $1 1 Investing in the Series A preferred stock round were MPM Capital, Burrill & Co. and the Malaysian Technology Development Corp. Protalix Biotherapeutics Ltd. Karmiel, Israel 7/17/05 $5.3 The Series C financing included investments from Tamares Capital, Docor International BV, Atara Technology Ventures Ltd. and returning investors Biocell Ltd., Marathon Investments Ltd. and private investors StemCyte Inc. Arcadia, Calif. 7/19/05 $13.7 Details on the financing round were not disclosed Vitae Fort Washington, Pa. Pharmaceuticals Inc. 7/13/05 $15 GlaxoSmithKline plc led the financing round, following the closing of a collaboration with Vitae; existing investors also participated Xention Discovery Ltd. 7/13/05 £1 1 ($20) The Series B financing round was led by new investor ABN AMRO Capital and included new investor Crédit Agricole Private Equity and existing investors MVM, Quester, BTG International, Isis Equity Partners, Albany Ventures and Enterprise VCT plc Cambridge, UK BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 107 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Baltimore 8/23/05 $30 SV Life Sciences and Alta Partners led the Series A round, which included HealthCap, Red Abbey Venture Partners, the Maryland Venture Fund and existing investors Esperance BioVentures, Astellas Ventures, Maryland TEDCO and Townsend Capital Alder BioSeattle pharmaceuticals Inc. 8/15/05 $1 1.1 The Series A financing was led by Sevin Rosen Funds and included Ventures West, WRF Capital and other investors Atonomics A/S Copenhagen, Denmark 8/1 1/05 €4.5 ($5.5) A second tranche of €4.5M is expected within two years; investors included Inventages, Murata, NeuroSearch A/S and Vaekstfonden; NeuroSearch gained a 20.16% stake in Atonomics in the deal Avacta Ltd. Leeds, UK 8/1 1/05 £0.3 ($0.54) IP2IPO Group invested £300,000 in the seed round of the Leeds University spinout CellTran Ltd. Sheffield, UK 8/2/05 £2.7 ($4.8) New investor YFM Group led the funding round, which included existing investors Biofusion plc and White Rose Seedcorn Fund and new investor Partnerships UK plc Cerenis Therapeutics SA Toulouse, France 8/22/05 $30.5 The Series A financing was led by Sofinnova Partners and HealthCap, and included Alta Partners, EDF Ventures and NIF Ventures Cerexa Inc. Alameda, Calif. 8/23/05 $50 Cerexa was spun out of Peninsula Pharmaceuticals Inc.; Frazier Healthcare Ventures and New Leaf Venture Partners co-led the Series A round, which included Domain Associates, Canaan Partners, OrbiMed Advisors, A.M. Pappas & Associates, Montreux Equity Partners, EGS Heathcare and CDIB BioScience Ventures Genoptix Inc. San Diego 8/10/05 $17.3 Chicago Growth Partners joined existing investors Enterprise Partners, Alliance Technology Ventures, Tullis-Dickerson & Co. Inc., U.S. Trust’s Excelsior Venture Partners III LLC and Lotus Bioscience Investment Holdings in the Series D financing round 8/30/05 $25 Inotek raised $25M in the first tranche of a planned $35M Series B round, which was led by Pitango Venture Capital and included existing investors Care Capital LLC, Rho Ventures and MedImmune Ventures Inc. AUGUST Alba Therapeutics Corp. Inotek Beverly, Mass. Pharmaceuticals Corp. 108 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Intercytex Ltd. Cambridge, UK 8/2/05 £12 ($21.5) Existing shareholders Avlar BioVentures, Merlin Biosciences, 3i, Cambridge Gateway Partnership, NIF Ventures and Scottish Equity Partners participated in Series C financing round ISTO Technologies Inc. St. Louis 8/31/05 $10.8 The financing package included equity and development funds; Zimmer Holdings Inc. led the financing round, which included Alafi Capital Co. LLC, Life Science Partners and Mid-America Transplant Services Karus Therapeutics Ltd. Southampton, UK 8/1/05 £0.75 ($1.35) The University of Southampton spinout received seed funding from IP2IPO and the SULIS fund MIP Technologies AB Lund, Sweden 8/23/05 SEK30 ($3.9) Catella Healthcare Investments AB led the financing round; Malmahus Invest and company management also participated Mpex San Diego Pharmaceuticals Inc. 8/1 1/05 $32 The Series B financing was led by SV Life Sciences and HBM BioVentures Ltd./HBM BioCapital LP and included other new investors Aberdare Ventures and Adams Street Partners and existing investors Western States Investment Group and Charitable Leadership Foundation OncoGenex Technologies Inc. Vancouver, British Columbia 8/16/05 $12.8 Participating in the company’s third financing round were existing investors Ventures West, H.I.G. Ventures, the Working Opportunity Fund and Business Development Bank of Canada and new investors WHI Morula Fund LLC and BC Advantage Funds Oxford Immunotec Ltd. Oxford, UK 8/3/05 £7 ($12.7) The Series B financing round was led by Prelude Ventures, and included Quester, the Dow Chemical Co. and Top Technology Profos AG Regensburg, Germany 8/23/05 €5 ($6.1) Bio Fund Management Ltd. led the financing round; existing shareholders Danisco Venture A/S and Capital Stage AG also participated Protez Malvern, Pa. Pharmaceuticals Inc. 8/24/05 $15 The Series B financing round was led by BioAdvance Ventures and Birchmere Ventures and included L Capital Partners, S.R. One and previous investor BTG Regado Biosciences Inc. 8/15/05 $20 The Series B financing was co-led by Domain Associates and Quaker BioVentures and included Aurora Funds and individual investors Research Triangle Park, N.C. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 109 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Speedel Group Basel, Switzerland 8/4/05 CHF70 ($55.5) Speedel raised CHF70M through a convertible loan that was subscribed to primarily by existing investors TargeGen Inc. San Diego 8/31/05 $30 The Series C financing round was led by BBiotech Venture and H&Q Healthcare Capital Management; also participating were existing investors Forward Ventures, Enterprise Partners, William Blair Capital Partners/Chicago Growth Partners, CDP Capital Technology Ventures/VantagePoint Venture Partners, China Development Industrial Bank, A.M. Pappas & Associates and others Tengion Inc. King of Prussia, Pa. 8/3/05 $39 Among the investors in the Series A round were Oak Investment Partners, Johnson & Johnson Development Corp., HealthCap and L Capital Partners A&G Pharmaceutical Inc. Columbia, Md. 9/8/05 $2 New England Partners led the Series A financing, which included the Maryland Venture Fund and Crocker Capital Algeta ASA Oslo, Norway 9/2/05 €23 ($28.7) Participating in the Series A financing were new investors HealthCap, Advent Venture Partners and S.R. One and existing investors Selvaag Venture Capital, NorgesInvestor, Marlin Verdi AS and several smaller investors Amicus Therapeutics Inc. Cranbury, N.J. 9/8/05 $55 Quaker BioVentures led the Series C financing and was joined by existing investors Canaan Partners, CHL Medical Partners, Frazier Healthcare Ventures, New Enterprise Associates, Prospect Venture Partners and Radius Ventures and new investors Palo Alto Investors and the Garden State Life Sciences Venture Fund Athenagen Inc. Menlo Park, Calif. 9/19/05 $3.2 The Series A financing was led by Sanderling Ventures and included Life Science Angels; another $2.5M in milestone-driven investments could be earned within 12 months Bioheart Inc. Sunrise, Fla. 9/27/05 $19 Participants in the Series D financing included Advent-Morro Equity Partners, The ASTRI Group, Magellan Group, Presidential Capital Partners, Dan Marino Investments, Minnesota Biomed Partners, New World Angels and individuals William P. Murphy and David Gury SEPTEMBER 110 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details Biolex Therapeutics Inc. Pittsboro, N.C. 9/1/05 $36 The Series B financing was led by Polaris Venture Partners and included existing investors Intersouth Partners, Quaker BioVentures, Johnson & Johnson Development Corp., Mitsui and Co. Venture Partners and Kitty Hawk Capital BioLineRx Ltd. Jerusalem 9/26/05 $9 Existing investors Giza Venture Capital, Pitango Venture Capital and Teva Pharmaceuticals Industries Ltd. committed to follow-on investments Cellerant Therapeutics Inc. San Carlos, Calif. 9/22/05 $9 Cellerant raised $9M in a second closing of its Series B round, bringing the total to $25M; in May it raised $16M in the first closing; participants in the second closing were Camelot Ventures, George Rathmann and Eminent Venture Capital Corp. Chiasma Inc. Jerusalem 9/12/05 $6.2 The Series B financing was co-led by F-2 Ventures and the Ofer Hi-Tech Group; Series A investors InnoMed Fund and Yissum Ltd. also participated Dimerix Bioscience Pty. Ltd. Perth, Australia 9/15/05 ND Foundation Capital led the Series A financing round, which included the Murdoch Westscheme Enterprise Partnership Fund; Startpharma Holdings Ltd. now owns 22% of Dimerix GlobeImmune Inc. Denver 9/14/05 $34.3 The Series B round was led by Lilly Ventures and included other new investors Medica Holdings, Adams Street Partners, Biogen Idec Inc., Genentech Inc., Partners Healthcare and GC&H Investments and existing investors HealthCare Ventures LLC, Morgenthaler Ventures and Sequel Venture Partners Kereos Inc. St. Louis 9/20/05 $19.5 New investors Prolog Ventures, Triathlon Medical Ventures and Charter Life Sciences, along with existing investor RiverVest Venture Partners, led the Series B round; also investing were Barnes-Jewish Hospital, Alafi Capital, Apjohn Ventures, Harris and Harris Group, Lux Capital, MB Venture Partners, Sigvion Capital, Vectis Life Science, Genentech Inc. and Royal Philips Electronics 9/7/05 $13.9 Investors in the Series A financing round included Latterell Venture Partners, U.S. Venture Partners, Morgenthaler Ventures and The Vertical Group OncoMed Mountain View, Calif. Pharmaceuticals Inc. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 111 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amount (M) Details PanGenetics BV Utrecht, the Netherlands 9/8/05 $2 The seed financing round was led by Index Ventures Pervasis Therapeutics Inc. Cambridge, Mass. 9/30/05 $12 The Series B financing round was led by new investor Highland Capital Partners and included founding investors Polaris Venture Partners and Flagship Venture Partners Replidyne Inc. Louisville, Colo. 9/8/05 $62.5 The Series D financing was led by Duquesne Capital Management, Healthcare Investment Partners and MDS Life Sciences Technology II funds and included existing investors HealthCare Ventures, TPG Ventures, Morgenthaler Ventures, Perseus-Soros BioPharmaceutical Fund, Sequel Venture Partners, Temasek Holdings Pte. Ltd. and Quintiles Transnational; Aquilo Partners Inc. was placement agent Respirics Inc. Raleigh, N.C. 9/27/05 ND Investors participating in the Series A financing included Catalysta Ventures and Research Triangle Ventures RioTech London Pharmaceuticals Ltd. 9/12/05 £0.75 ($1.35) Details on the financing round were not disclosed SpinX Technologies Geneva 9/6/05 €10 ($12.4) The Series B financing round was led by Bio Fund Management, with participation from existing investor Index Ventures, as well as from Auriga Partners, DFJ ePlanet Ventures and the CERN Pension Fund Teranode Corp. Seattle 9/12/05 $9.5 The Series B round was led by Cargill Ventures and Trident Capital; Series A investors Ignition Partners and WRF Capital also participated Xigen SA Lausanne, Switzerland 9/6/05 CHF21 ($26) Investors in the Series A financing round were Tilocor Life Sciences, Venture Incubator and Initiative Capital Aerie Research Triangle Pharmaceuticals Park, N.C. Inc. 10/12/05 $21 The Series A financing round was led by Alta Partners and Texas Pacific Group Ventures Alinea Cambridge, Mass. Pharmaceuticals Inc. 10/20/05 $45 The Series A financing was led by MPM Capital and included SV Life Sciences, Flagship Ventures and Burrill & Co., which helped structure the deal OCTOBER 112 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amt. (M) Details AM-Pharma BV Bunnik, the Netherlands 10/31/05 €9 ($10.8) Inventages Venture Capital Investments Inc. invested €6 and ABN-AMRO Life Sciences Capital invested €3M in the Series B financing round Cadence San Diego Pharmaceuticals Inc. 10/1 1/05 $25 The Series A financing round was led by Domain Associates and included ProQuest Investments, BB Biotech Ventures, CDIB BioScience Venture Management, Windamere Venture Partners and private investors Cardium Therapeutics Inc. 10/20/05 $28.5 The money was raised concurrent with a reverse merger with Aries Ventures Inc. (OTC BB: ARVT) and the acquisition of cardiovascular product candidates from Schering AG Cerimon South San Francisco Pharmaceuticals Inc. 10/26/05 $70 The Series A financing round was led by MPM Capital, together with Nomura Phase4 Ventures and OrbiMed Advisors CODA Genomics Inc. Irvine, Calif. 10/5/05 $0.8 Tech Coast Angels provided the investment in the Series A financing round Cyclacel plc Dundee, UK 10/10/05 £5 ($8.9) Scottish Enterprise invested £5 million in the form of a convertible loan; it is making £2.5 million more available if matched by the private sector Epistem Ltd. Manchester, UK 10/24/05 £1.72 ($3) The company raised £1.72 million through a private placing by Zeus Capital ForteBio Inc. Menlo Park, Calif. 10/26/05 $17.3 The Series B financing round was led by The Vertical Group; existing investors Agilent Ventures, Alloy Ventures, Latterell Venture Partners and Versant Ventures also participated GlycoFi Inc. Lebanon, N.H. 10/10/05 $1 1 The financing was an extension of a $10M Series C financing that closed in December 2003; participating were existing investors Polaris Venture Partners, SV Life Sciences, Boston Millenia Partners, Fletcher Spaght Ventures, Village Ventures and Borealis Ventures and new investors International Biotechnology Trust, Peninsula Equity Partners and Eli Lilly and Co. Kereos Inc. St. Louis 10/14/05 $0.5 Advantage Capital Partners added $0.5M to the $19.5M Series B round completed in September Kinexis Inc. Carlsbad, Calif. 10/14/05 $0.9 InvestBio Ventures AmpliMed GP made the investment in Kinexis San Diego BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 113 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amt. (M) Details Light Sciences Oncology Inc. Seattle 10/12/05 $35 The company was spun out of Light Sciences Corp. in connection with the Series A financing; Essex Woodlands Health Ventures led the round, which included Adams Street Partners, Johnson and Johnson Development Corp., China Development Industrial Bank and Larkspur Capital Corp., which acted as adviser in the deal Marinus Branford, Conn. Pharmaceuticals Inc. 10/25/05 $29.4 The Series A financing round was led by Domain Associates, Sofinnova Ventures and Canaan Partners; Foundation Medical Partners and private investors also participated Molecular Profiling Institute Inc.* Phoenix 10/28/05 $7.5 Investing the Series B financing round were AmeriPath, Affymetrix Inc. and Gen-Probe Inc. Opal Therapeutics Inc. Melbourne, Australia 10/25/05 $6 The Series A financing was led by GBS Venture Partners, and included Alloy Ventures, Alta Partners and Uniseed Predicant Biosciences South San Francisco 10/1 1/05 $7.5 Hercules Technology Growth Capital Inc. provided $7.5 million of debt financing to Predicant ProNAi Therapeutics Inc. Kalamazoo, Mich. 10/19/05 $4.25 ProNAi raised $2.5M in a Series A financing that included Biosciences Research Commercialization Center at Western Michigan University, Apjohn Ventures and the Grand Angles; it also raised $1.75M from a convertible note from the state of Michigan’s Technology Tri-Corridor Raven South San Francisco Biotechnologies Inc. 10/12/05 $48.3 The Series D round was led by new investor Vulcan Capital and included new investors Biogen Idec New Ventures, CIDC Consultants Inc. and Mitsubishi UFJ Capital Co. Ltd. and existing investors Bear Stearns Health Innoventures LP, Pequot Ventures, Singapore’s BioMedical Sciences Investment Fund Pte. Ltd., Integra Ventures, U.S. Venture Partners, CMEA Ventures, Hambrecht & Quist Capital Management LLC, Milepost Ventures and Cogene Ventures Serenex Inc. Durham, N.C. 10/6/05 $30 The Series C financing round was led by Ritchie Capital and included existing investors Intersouth Partners, Lilly Ventures, Mediphase Venture Partners, Takeda Research Investment and Seaflower Ventures Stokes Bio Ltd. Cork, Ireland 10/12/05 €1 ($1.2) The first-round funding was provided by Kernel Capital Partners 114 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amt. (M) Details Surface Logix Inc. Boston 10/28/05 $32 Surface Logix closed on $32M of a planned $42M Series D round; the other $10M is contingent on reaching milestones; participating were existing investors Venrock Associates, Arch Venture Partners, CW Group, HBM Partners, TIAA-CREF, Healthcare Focus Fund and Intel Capital and new investor Unilever Technology Ventures Tessera Inc. Seattle 10/3/05 $8.5 The company completed a Series B financing round The Vaccine Co. LP New York 10/21/05 $14 InvestBio Ventures raised $14M of a planned $20M investment in the company; InvestPrivate Inc. was placement agent in the deal Tigris New York Pharmaceuticals Inc. 9/22/05 $1 1.6 The company completed a Series A financing round, which included the conversion of about $1.6M of previously issued debt Topigen Montreal Pharmaceuticals Inc. 10/6/05 C$6 ($5.1) The C$6M second closing brought the Series B total to C$28.6; Caisse de depot et placement du Quebec invested in the second closing TransOral Corte Madera, Calif. Pharmaceuticals Inc. 10/28/05 $23 The Series C round was led by New Leaf Venture Partners and included InterWest Partners, Montreux Equity Partners, Peninsula Equity Partners, Hamilton BioVentures and Vivo Ventures Trigen Holdings AG London 10/1 1/05 €26.5 ($31.7) The second-round financing was co-led by Wellington Partners, HealthCap and 3i and included SR One, Quintiles PharmaBio Development, Quest for Growth, BIT, Merifin and others VirXsys Corp. Gaithersburg, Md. 10/1 1/05 $31 The company completed the final closing of its Series F financing round Xencor Inc. Monrovia, Calif. 10/18/05 $20 The Series D financing round was led by Zen Investments New York 1 1/29/05 $8 Canaan Partners and Wheatley Partners co-led the Series B financing, which also included existing investors; Walter Greenblatt & Associates LLC was financial adviser NOVEMBER Advanced BioHealing Inc. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 115 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amt. (M) Details Alimera Sciences Inc. Atlanta 1 1/30/05 $31.8 The Series B financing round was led by Venrock Associates and included original investors BA Venture Partners, Domain Associates, Intersouth Partners and Polaris Venture Partners Antisense Pharma GmbH Regensburg, Germany 1 1/30/05 $18 The investment was provided by German MIG funds CeNeRx BioPharma Inc. Research Triangle Park, N.C. 1 1/29/05 $18.5 The Series A financing round was led by PerseusSoros BioPharmaceutical Fund, with participation from L Capital Partners, A.M. Pappas & Associates and Wistar Morris CytImmune Sciences Inc. Rockville, Md. 1 1/15/05 $5 The financing was a combination of a private investment and state funding from Maryland’s Department of Business and Economic Development Edison San Jose, Calif. Pharmaceuticals Inc. 1 1/29/05 $2.8 The Series A round was led by Paul Avery 4SC AG 1 1/30/05 €10.16 ($1 1.9) The pre-listing financing entailed the sale of about 2.4M shares at €4.24 per share; Conrad Hinrich Donner Bank AG coordinated the deal Fovea Paris Pharmaceuticals SA 1 1/7/05 €20.5 ($24.5) The Series A financing round was led by Sofinnova Partners and included Abingworth Management, The Wellcome Trust, GIMV and Credit Agricole Private Equity Gene-IT Inc. Worcester, Mass. 1 1/30/05 $4.1 The Series A financing was led by Cross Atlantic Partners and Milestone Venture Partners, and included Société Générale Asset Management Alternative Investments Guava Technologies Inc. Hayward, Calif. 1 1/29/05 $7 The financing was provided by existing investors Abingworth Life Science Investment, Granite Global Ventures, HLM Venture Partners, MDS Capital Corp., ProQuest Investments and Skyline Ventures 1 1/17/05 $10 Inotek raised $10M in the second tranche of a $35M Series B financing; $25M was raised In August; new investors included Caisse de depot et placement du Quebec and Pitango Venture Capital Martinsried, Germany Inotek Beverly, Mass. Pharmaceuticals Corp. 116 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amt. (M) Details IntegraGen SA Evry, France 1 1/17/05 €8 ($9.4) Investors in the Series B financing round included CDC Enterprises Innovation, AGF Private Equity, Bioam, SGAM Alternative Investments and Baytech Venture Capital iQur Ltd. Southampton, UK 1 1/8/05 £2.6 ($4.5) Details on the £2.6 follow-on financing were not disclosed; the company formerly was named HepCgen Ltd. Lentigen Corp. Baltimore 1 1/30/05 ND The company secured undisclosed seed and Series A financing from Greenwich Biotech Ventures Mersana Therapeutics Inc. Cambridge, Mass. 1 1/8/05 $21 Fidelity Biosciences and ProQuest Investments led the financing round; also participating were Rho Ventures and previous investors PureTech Ventures, Cape Family Fund LLC, Harris & Harris Group Inc. and Lansing Brown Investments LLC NuPathe Inc. Conshohocken, Pa. 1 1/8/05 $0.5 BioAdvance, the Biotechnology Greenhouse of Southeastern Pennsylvania, led the seed funding round OncoMethylome Leige, Belgium Sciences SA 1 1/2/05 €15 ($17.7) The Series B financing round was led by Edmond de Rothschild Investment Partners; existing investors ING Belgium, Life Sciences Partners, PolyTechnos Venture-Partners, Meusinvest and Technowal also participated Portola South San Francisco Pharmaceuticals Inc. 1 1/8/05 $46 The Series B financing round was led by Advanced Technology Ventures; also participating were Alta Partners and previous investors Abingworth Management, Frazier Healthcare Ventures, MPM Capital, Prospect Ventures and Sutter Hill Ventures PTC Therapeutics Inc. 1 1/10/05 $26.6 The financing was led by existing investors Credit Suisse First Boston Private Equity and HBM BioVentures, with participation from Vulcan Ventures, Novo A/S, Delphi Ventures, Bay City Capital, Novartis BioVentures, Amgen Ventures and HealthCap Rincon San Diego Pharmaceuticals Inc. 1 1/15/05 $4.7 The financing was led by Paperboy Ventures Spear Therapeutics Ltd. 1 1/28/05 $8.5 Advent International invested in the financing round South Plainfield, N.J. London BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 117 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amt. (M) Details Syntaxin Ltd. Salisbury, UK 1 1/15/05 £3 ($5.2) Abingworth Management Ltd. invested in the company, which was spun out from the UK Health Protection Agency Vital Therapies Inc. San Diego 1 1/1/05 $8 MedVenture Associates led the first closing of a Series B financing; also participating were Valley Ventures, Paragon Venture Partners, Toucan Capital and individual investors Acologix Inc. Hayward, Calif. 12/20/05 $25.3 Participating in the Series C financing were existing investors Tokio Marine & Nichido Fire Insurance Co. Ltd., JAIC America and Nomura Research and Advisory Co. Ltd. and new investors Nomura Securities Co. Ltd. and UOB JAIC Venture Bio Investments Ltd. AngioChem Inc. Laval, Quebec 12/12/05 C$6 ($5.2) The financing was led by BDC Venture Capital and VIMAC Milestone Medica Fund BioAxone Therapeutic Inc. Montreal 12/19/05 $5.1 The $5.1M tranche completed a second-round funding of $12.15M; investors were T2C2/Bio2000, Solidarity Fund QFL, Desjardins Venture Capital and Lothian Partners 27 SARL; the initial tranche was completed in July 2002 Celladon Corp. La Jolla, Calif. 12/7/05 $30 The Series B financing was led by new investors Kleiner Perkins Caufield & Byers and Domain Associates; existing investors Enterprise Partners Venture Capital and Venrock Associates also participated Cellartis AB Gothenburg, Sweden 12/13/05 €8 ($9.6) New investor Bio Fund Management Ltd. led the financing round, which included existing investors InnovationsKapital, Catella Healthcare Investments, T-bolaget, Texcel and Barnwik AB Domantis Ltd. Cambridge, UK 12/1 1/05 £17 ($29) New investors Novo Nordisk and MC Life Science Ventures Inc. joined existing investors in the Series B financing round Gastrotech Pharma A/S Copenhagen, Denmark 12/6/05 €2.3 ($2.7) Bioscience Managers Ltd. and Nordic Biotech participated in the financing round DECEMBER 118 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amt. (M) Details Hypnion Inc. Lexington, Mass. 12/19/05 $20.1 Investors in the extension of a Series B financing round included MPM Capital, Advanced Technology Ventures, Forward Ventures, Flagship Ventures, Oxford Bioscience Partners, GIMV, S.R. One Ltd., JAFCO, Alexandria Real Estate Equities and Mintz Levin Investments; $47.5M was raised in the first Series B tranche in March 2003 ImaRx Therapeutics Inc. Tucson, Ariz. 12/16/05 $15 Details on the financing were not disclosed InsectiGen Atlanta 12/12/05 $1.2 Investing in the financing round were Georgia Venture Partners Seed Fund, the Georgia Biosciences Seed Capital Fund and individuals KeyNeurotek AG Magdeburg, Germany 12/13/05 €7.75 ($9.3) The financing was completed along with the merger with Sirenade Pharmaceuticals AG; DVC Deutsche Venture Capital led the round, which included IBG Beteiligungsgesellschaft Sachsen-Anhalt and tbg/KfW Light Sciences Oncology Inc. Seattle 12/14/05 $32 The $32M was a second closing of the Series A round; the first closing of $35M was completed in October; investing in the second closing were Essex Woodlands Health Ventures, Scandinavian Life Science Venture, Novo A/S and New Science Ventures NeurogesX Inc. San Carlos, Calif. 12/1/05 $20 Investing in the extension of the Series C round were MC Life Science Ventures, MunMun International Ltd., Saudi Venture Development Co. and existing investors ARCH Venture Partners, Alta Partners, Montreux Equity Partners, Global LifeScience Ventures and Walden International Venture Partners Optimer San Diego Pharmaceuticals Inc. 12/14/05 $22.4 Investing in the Series D financing round were ProQuest Investments, Lurie Investments, BB Biotech Ventures, SB Life Science Ventures, UOB JAIC Venture Bio Investments, China Development Industrial Bank, ESun Bank Group, Fubon Financial Holding Venture, Global Strategic Investments, Oriental Union Chemical Corp. and Taiwan Global BioFund Osiris Therapeutics Inc. 12/21/05 $19 The financing round was arranged by Friedli Corporate Finance Inc. Baltimore BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 119 2005 Venture Capital And Other Financings Of Private Biotechnology Firms (Continued) Company Location Date Amt. (M) Details Santhera Liestal, Switzerland Pharmaceuticals AG 12/20/05 CHF25 ($19) Investors in the Series B financing included NGN Capital, Oxford Bioscience Partners, Varuma AG, Merlin Bioscience Ltd., 3i Group plc, Carnegie Asset Management, GIMV, the Novartis Venture Fund, Dow Chemical Co., Clariden Biotechnology Fund, Heidelberg Innovation and the Swiss Foundation for Research of Muscle Disease Solazyme Inc. Menlo Park, Calif. 12/21/05 ND The Roda Group invested in the financing round, details of which were not disclosed Therion Biologics Corp. Cambridge, Mass. 12/27/05 $50 Therion secured a $50M line of credit from Hans-Werner Hector, providing funding for the company into 2007 Notes: ND = Not disclosed. 120 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Abgenix Inc. (ABGX) Amgen Inc. (AMGN) ND Milestone payment Triggered by Amgen’s advancement into clinical trials of an undisclosed antibody created using Abgenix’s XenoMouse technology (1/13) Abgenix Inc. (ABGX) Chiron Corp. (CHIR) ND Milestone payment Triggered by Chiron’s filing of an IND for a fully human antibody, CHIR-12.12, targeting CD40 that was created using Abgenix’s XenoMouse technology (1/12) Abgenix Inc. (ABGX) Human Genome Sciences Inc. (HGSI) ND Milestone payment Triggered by HGS’ filing of an IND for a fully human antibody to the CCR5 receptor created using Abgenix’s XenoMouse technology (1/10) Alnylam Merck & Co. Inc. Pharmaceuticals Inc.* $7 Milestone payment $5M of the payment was made in stock and $2M in cash; it was triggered by development of in vivo RNAi technology to a prespecified level of performance (1/3) ArQule Inc. (ARQL) Wyeth ND Milestone payments Payments were triggered by Wyeth beginning development of a compound for Alzheimer’s disease and for progress on a compound for rheumatoid arthritis (1/10) Avant Immunotherapeutics Inc. (AVAN) GlaxoSmithKline plc (UK) $2 Milestone payment The acceptance for review by European regulatory authorities of a marketing application for the Rotarix rotavirus vaccine triggered the milestone (1/6) Galapagos Genomics NV* (Belgium) Boehringer Ingelheim GmbH (Germany) ND Milestone payment BI licensed targets in viral replication that were discovered using Galapagos’ SilenceSelect gene knockdown platform (1/20) Karo Bio AB (Sweden; SSE:KARO) Merck & Co. Inc. ND Milestone payment Triggered by initiation of clinical trials for the most advanced compound from their collaboration focused on estrogen receptors (1/21) NeuroSearch A/S (Denmark; CSE:NEUS) Boehringer Ingelheim GmbH (Germany) $5 Milestone payment Triggered by continued development of NS2330 for treating Alzheimer’s and Parkinson’s diseases; it is in Phase II trials (1/24) JANUARY BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 121 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Novogen Ltd. (Australia; NVGN) Solae LLC $0.86 Milestone payment The milestone was paid as part of its license to certain Novogen soy isoflavone technology (1/18) Pharmos Corp. (PARS) Bausch & Lomb $12.1 Milestone payment Triggered by B&L’s launch of Zylet, which was part of the loteprednol etabonate business Pharmos sold to B&L in 2001 (1/23) Regeneron Sanofi-Aventis Pharmaceuticals Group (France) Inc. (REGN) $25 Milestone payment The payment was made in connection with clinical development of VEGF Trap in cancer indications (1/10) Vernalis plc (UK; VNLS) Serono SA (Switzerland; NYSE:SRA) ND Milestone payment Triggered by Serono’s initiation of a Phase I trial of their selective inhibitor of MMP-12, which is being developed for inflammatory diseases (1/19) Affitech A/S* (Norway) Peregrine Pharmaceuticals Inc. (PPHM) ND Milestone They are collaborating on antibodies that block VEGF; it was not clear if the milestone triggered a payment (2/14) Affitech A/S* (Norway) Viventia Biotech Inc. (Canada; TSE:VBI) ND Milestone payment Triggered by Affitech’s discovery and selection of several cancer antibodies, and the subsequent screening of them using Viventia’s antibody profiling platform (2/2) Astex Technology Ltd.* (UK) Boehringer Ingelheim GmbH (Germany) ND Milestone payment Astex achieved the first milestone in a collaboration under which it is applying its Pyramid technology for drug discovery (2/14) Cardiome Pharma Ltd. (Canada; CRME) Fujisawa Healthcare Inc. $6 Milestone payment Triggered by completion of ACT 1, the first of three Phase III trials of Cardiome’s antiarrhythmic product, intravenous RSD1 235 (2/23) Cellular Genomics Inc.* Serono SA (Switzerland; NYSE:SRA) ND Milestone payment Triggered by successful development of CGI’s in vivo models for kinase drug discovery under their collaboration (2/15) A$0.72 ($0.56) Milestone payment ChemGenex reached a research milestone in its depression target discovery program with Vernalis (2/23) FEBRUARY ChemGenex Vernalis plc Pharmaceuticals (UK; VNLS) Ltd. (Australia; (ASX:CXS) 122 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Diversa Corp. (DVSA) Syngenta AG (Switzerland) $0.5 Milestone payment Diversa successfully delivered to Syngenta multiple qualified enzyme candidates for use as animal feed additives (2/14) Ligand GlaxoSmithKline Pharmaceuticals plc (UK) Inc. (LGND) $1 Milestone payment Triggered by GSK’s start of Phase II trials of SB4971 15, a small-molecule drug that mimics the activity of thrombopoietin, which promotes production of blood platelets (2/7) Medarex Inc. (MEDX) Amgen Inc. (AMGN) ND Milestone payment Triggered by Amgen’s advancement into clinical trials of an antibody developed using Medarex’s UltiMAb technology (2/24) MorphoSys AG (Germany; FSE:MOR) GPC Biotech AG (Germany; CPGB) ND Milestone payment Triggered by GPC’s initiation of a Phase I trial of the anticancer monoclonal antibody 1D09C3, which was generated using MorphoSys’ technology (2/1) Nastech Pharmaceutical Co. Inc. (NSTK) Questcor Pharmceuticals Inc. $2 Milestone payment Triggered by FDA approval of Nascobal Nasal Spray for treating vitamin B-12 deficiency; Nastech sold rights to Questor in 2003 (2/1) Nautilus Serono SA Biotech* (France) (Switzerland; NYSE:SRA) ND Milestone payment A milestone was reached in a collaboration to develop a next-generation human growth hormone with an improved pharmacological profile (2/22) Phytopharm plc (UK; LSE:PYM) Yamanouchi Pharmaceutical Co. Ltd. (Japan) £4 ($7.7) Milestone payment Triggered when a trial of PYM50028 (Cogane) for Alzheimer’s disease in 60 subjects met safety criteria set out in their licensing agreement (2/28) Santarus Inc. (SNTS) TAP Pharmaceutical Products Inc. $10 Milestone payment Santarus said it is entitled to the payment after prevailing in an alternative dispute resolution proceeding concerning a June 2002 sublicensing agreement (2/15) TopoTarget A/S* (Denmark) CuraGen Corp. (CRGN) ND Milestone payment Triggered by initiation of Phase II trials of PXD101 in multiple myeloma (2/1) $8 Equity investment Kos and its chairman each invested $4M; Kos owns 27% of the company, with which it has been collaborating on chemical entities that regulate HDL cholesterol; another $4M each would be paid in 18 months if milestones are reached; a consortium led by Kos’ chairman owns 48% of Triad (2/7) Triad Kos Pharmaceuticals Pharmaceuticals Inc.* Inc. (KOSP) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 123 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Dynavax Technologies Corp. ND Milestone payment BioSeek used its BioMAP Systems to characterize the biological activity of a family of TNFalpha inhibitors known as thiazolopyrimidines for Dynavax (3/2) Caprion Abbott Pharmaceuticals Laboratories Inc.* (Canada) ND Milestone payment Triggered by Abbott’s acceptance of the final data set of tumor antigen targets that were discovered by Caprion (3/21) Curis Inc. (CRIS) ND Milestone payment Triggered by progress in preclinical development of Hedgehog pathway agonists for treating stroke, neurological and other disorders under their 2004 deal (3/23) Enanta Shionogi & Co. Pharmaceuticals Ltd. (Japan) Inc.* ND Milestone payment Triggered by Shiongi’s initiation of Phase I trials in Japan for the community antibiotic EP-013420 (3/14) Icagen Inc. (ICGN) Yamanouchi Pharmaceutical Co. Ltd. (Japan) ND Milestone payment Triggered by selection of a compound for advanced preclinical studies from their collaboration in dementia (3/15) ImmunoGen Inc. (IMGN) Sanofi Aventis Group (France) $2 Milestone payment Triggered by Sanofi Aventis’ initiation of clinical testing of the anti-CD33 TumorActivated Prodrug compound huMy9-6-DM4, which it licensed from ImmunoGen (3/17) InKine Pharmaceutical Co. Inc. (INKP) Zeria Pharmaceutical Co. Ltd. (Japan) $1 Milestone payment Triggered by Zeria’s submission of a new drug application in Japan for use of sodium phosphate tablets as a colonic purgative, bowel cleansing agent or laxative (3/29) Maxygen Inc. (MAXY) Hoffmann-La Roche Inc. ND Milestone payment The payment was triggered by progress in their collaboration to develop improved interferon alpha protein therapeutics to treat hepatitis C virus (3/30) Millennium Johnson & Johnson Pharmaceuticals Pharmaceutical Inc. (MLNM) Research and Development LLC $20 Milestone payments Two $10M payments were triggered by achievement of thresholds in year-to-date Velcade sales outside the U.S. (3/7) Millennium GlaxoSmithKline Pharmaceuticals plc (UK) Inc. (MLNM) $19.9 Milestone payment Triggered by the successful transfer of the central marketing authorization of Integrrilin in Europe to GSK and related activities (3/7) MARCH BioSeek Inc.* 124 Wyeth Pharmaceuticals BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) NeuroSearch A/S (Denmark; CSE:NEUS) GlaxoSmithKline plc (UK) €10 ($13) Milestone payment Triggered by GSK’s decision to initiate a Phase II trial of NS2359 (GSK372475) for the treatment of depression (3/29) Orphan Medical Inc. (ORPH) UCB Pharma (Belgium) $1 Milestone payment Triggered by submission of a supplemental NDA to the FDA seeking approval of Xyrem for reducing excessive daytime sleepiness and improving fragmented sleep in narcolepsy patients (3/21) Proteome Systems (Australia; ASX: PXL) High Q Foundation $0.3 Milestone payment Triggered by identification of the first candidate biomarkers for Huntington’s disease in clinical samples of plasma and cerebrospinal fluid (3/31) Seattle Genetics Inc. (SGEN) Genentech Inc. ND Milestone payment The milestone is based on Genentech’s preclinical progress in development of an antibody-drug conjugate using Seattle Genetics’ technology (3/15) Supratek Pharma Inc.* (Canada) Bioaccelerate Holdings Inc. $5 Equity investment Bioaccelerate made a $5M equity investment in Supratek, with which it is developing cancer drugs (3/24) Vicuron Novartis Pharmaceuticals Pharma AG Inc. (MICU) (Switzerland) ND Milestone payment Triggered by follow-up lead product candidates by Novartis from collaboration focused on peptide deformylase inhibitors (3/4) Zealand Sanofi Aventis Pharmaceuticals Group (France) A/S* (Denmark) ND Milestone payment Triggered by Sanofi’s successful completion of Phase IIa trials of AVE0010, a GLP-1 agonist it licensed from Zealand (3/3) $10.5 Warrants exercise Celgene exercised 7M warrants at $1.50 each that it received in a December 2002 deal in which EntreMed licensed its thalidomide analogue program to Celgene (4/1) Ligand TAP Pharmaceuticals Pharmaceuticals Inc. (LGND) Products Inc. $1.5 Milestone payment Triggered by TAP’s submission of an IND to evaluate LGD2941, a product from their collaboration, for treating osteoporosis and frailty (4/4) Maxim Myriad Pharmaceuticals Genetics Inc. Inc. (MAXM) $1 Milestone payment Triggered by dosing of the first patient in Myriad’s Phase I program to evaluate safety and pharmacokinetics of MPC-6827 in patients with advanced solid tumors (4/27) APRIL EntreMed Inc. (ENMD) Celgene Corp. (CELG) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 125 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Pharmacopeia Inc. (PCOP) Schering-Plough Corp. ND Milestone payment Triggered by Schering-Plough’s initiation of preclinical development of a small-molecule drug candidate identified in their collaboration targeted at inflammatory disease (4/13) Active Biotech AB* (Sweden) Avidex Ltd.* (UK) ND Milestone payment Triggered by initiaton of Phase I trials of RhuDex in rheumatoid arthritis (5/9) Array BioPharma Inc. (ARRY) Amgen Inc. (AMGN) $1 Milestone payment The research milestone payment resulted from their January 2002 drug discovery agreement (5/10) Atugen AG* (Germany) Schering AG (Germany) ND Milestone payments Atugen said it has achieved nine milestones under its target validation deal with Schering; financial details were not disclosed (5/9) Celgene Corp. (CELG) Novartis Pharma AG (Switzerland) ND Milestone payments Triggered by Novartis gaining FDA approval to market Focalin XR extended-release capsules for treating attention deficit hyperactivity disorder (5/27) Cytos Biotechnology AG (Switzerland; SWX:CYTN) Novartis Pharma AG (Switzerland) ND Milestone payment Triggered by approval in Sweden for Novartis to start a Phase I trial of the Immunodrug CAD106, an immunotherapeutic for treating Alzheimer’s disease (5/18) Exelixis Inc. (EXEL) GlaxoSmithKline plc (UK) $35 Milestone payments A $30M milestone was triggered by submission of INDs for the cancer agents XL880, XL820 and XL844; a $5M milestone payment was triggered by progress in earlier-stage programs in their collaboration (5/9) GW Bayer Healthcare Pharmaceuticals AG (Germany) plc (UK; LSE:GWP) £1 ($1.8) Milestone payment Triggered by approval in Canada of Sativex for symptomatic relief of neuropathic pain in multiple sclerosis (5/1 1) Memory F. Hoffmann-La Pharmaceuticals Roche Ltd. Corp. (MEMY) (Switzerland) $2 Milestone payment Roche made the milestone payment to maintain its option to obtain an exclusive license to MEM 3454, a nicotinic alpha-7 receptor agonist in Phase I trials (5/3) Myogen Inc. (MYOG) ND Milestone payments Myogen achieved three milestones related to progress in validation of high-throughput assays in their 2003 collaboration focused on drugs for cardiovascular disease (5/26) MAY 126 Novartis AG (Switzerland) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Neose Technologies Inc. (NTEC) Novo Nordisk A/S (Denmark) ND Milestone payment Neose received a scheduled payment under their 2003 deal to apply Neose’s GlycoPEGylation technology to a Novo protein (5/13) Pharmacopeia Drug Discovery Inc. (PCOP) NV Organon (the Netherlands) ND Milestone payment Triggered by Organon’s initiation of toxicological studies of a development candidate from the collaboration (5/25) Rigel Daiichi Pharmaceuticals Pharmaceuticals Inc. (RIGL) Co. Ltd. (Japan) ND Milestone payments The two payments were triggered by Daiichi’s selection of two small-molecule compounds from their August 2002 collaboration to identify candidates against a ligase target for cancer indications (5/5) SkyePharma plc (UK; SKYE) First Horizon Pharmaceutical Corp. $15 Milestone payment Triggered by FDA approval of Triglide, a formulation of the cardiovascular product fenofibrate; First Horizon has marketing rights (5/9) Sucampo Takeda Pharmaceuticals Pharmaceutical Inc.* Co. Ltd. (Japan) $20 Milestone payment Triggered by initiation of a Phase III trial of lubiprostone in constipation-predominant irritable bowel syndrome (5/16) JUNE Archemix Corp.* Eyetech Pharmaceuticals Inc. (EYET) ND Milestone payment Eyetech selected a preclinical candidate from their 2004 collaboration; it is an aptamer directed against platelet-derived growth factor for use in neovascular age-related macular degeneration (6/22) Avantogen Ltd. (Australia; ASX:ACU) Endocyte Inc.* ND Milestone payment Triggered by Avantogen’s submission of a drug master file to the FDA for the vaccine adjuvant GPI-0100, for use in treating kidney cancer (6/15) Codexis Inc.* Pfizer Inc. ND Milestone payment Codexis reached a milestone in their July 2004 deal focused on applying Codexis’ process R&D platform to certain Pfizer small molecules (6/1) Depomed Inc. (DEPO) Biovail Corp. (Canada) $25 Milestone payment Triggered by receipt of an approval letter from the FDA for Glumetza for treating Type II diabetes (6/3) Diversa Corp. (DVSA) XOMA Ltd. (XOMA) ND Milestone payment Triggered by successful generation of an antibody that binds with sub-picomolar affinity to an undisclosed XOMA target (6/1) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 127 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Evotec OAI AG (Germany; FSE:EVT) Boehringer Ingelheim GmbH (Germany) ND Milestone payment Triggered by identification of a number of lead series for a priority target in their collaboration (6/7) Innate Pharma SAS* (France) Novo Nordisk A/S (Denmark) ND Milestone payment The milestone relates to an antibody candidate specific for an NK cell receptor discovered under their November 2003 alliance (6/20) Ligand GlaxoSmithKline Pharmaceuticals plc (UK) Inc. (LGND) $2 Milestone payment Triggered by GSK’s filing of an IND for SB559448, a small-molecule drug that mimics the activity of thrombopoietin (6/6) NeoPharm Inc. (NEOL) Unnamed private biotech company $0.35 Milestone payment NeoPharm provided customized NeoPhectin (liposomal) formulations for the partner’s compounds (6/23) Sareum Holdings plc (UK; AIM:SRA) Undisclosed UK-based company ND Milestone payment Triggered by delivery of structural data under their December 2004 collaboration (6/30) Speedel Group* (Switzerland) Locus Pharmaceuticals Inc.* ND Milestone payment Speedel produced a series of lead compounds (SPP800 series) under their 2003 collaboration on renin inhibitors for treating cardiovascular and metabolic diseases (6/16) Arena Merck & Co. Inc. Pharmaceuticals Inc. (ARNA) $2 Milestone payment Triggered by Merck’s initiation of a Phase I trial of an oral drug candidate for treating atherosclerosis and related disorders (7/26) Diversa Corp. (DVSA) DuPont Bio-Based Materials $0.5 Milestone payments Two milestones were met relating to delivery by Diversa of candidate enzymes under their biorefinery program that exceeded performance targets set by the Department of Energy (7/1 1) Emisphere Technologies Inc. (EMIS) Hoffmann-La Roche Inc. ND Milestone payment Roche began a clinical trial using Emisphere’s eligen delivery technology under their deal to develop oral formulations of a Roche smallmolecule compound for treating bone-related diseases (7/5) 454 Life Sciences (majority owned by CuraGen Corp.; CRGN) F. HoffmannLa Roche Ltd. (Switzerland) $1 1.5 Milestone payments 454 achieved all initial milestones under a May 2005 deal in which Roche is selling 454’s Genome Sequencing Systems (7/26) JULY 128 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Inovio Biomedical Corp. (AMEX:INO) Merck & Co. Inc. $2 Milestone payment Merck reached a clinical milestone on a plasmid-based vaccine using Inovio’s MedPulser DNA Delivery System under their May 2004 collaboration (7/13) Ligand Eli Lilly and Co. Pharmaceuticals Inc. (LGND) $1.6 Milestone payment Triggered by Lilly’s initiation of Phase II studies on LY674, a peroxisome proliferation activated receptor modulator for the treatment of atherosclerosis (7/13) Onyx Bayer Pharmaceuticals Pharmaceuticals Inc. (ONXX) Corp. $10 Milestone payment Triggered by the submission of an NDA with the FDA for sorafenib (BAY 43-9006) for treating advanced renal-cell carcinoma (7/1 1) Transgene SA (France; TRGNY) ND Milestone payment Triggered by Phase I trials by Merck of a vaccine constructed with Transgene’s homologous recombination technology (7/21) Anadys Novartis AG Pharmaceuticals (Switzerland) Inc. (ANDS) $10 Milestone payment Triggered by FDA acceptance of the IND to start testing ANA975, an oral Toll-like receptor 7 agonist for treating hepatitis C (8/18) Cenix Bayer HealthCare BioScience AG (Germany) GmbH* (Germany) ND Milestone payment The payment stemmed from delivery by Cenix of a collection of potential therapeutic targets under its deal with Bayer (8/9) Human Genome Sciences Inc. (HGSI) GlaxoSmithKline plc (UK) $7 Milestone payments HGSI got payments for reaching manufacturing and preclinical development milestones on the diabetes candidate GSK716155 (formerly Albugon), which is covered under a 2004 deal (8/1) MorphoSys AG (Germany; FSE:MOR) Novartis AG (Switzerland) ND Milestone payment MorphoSys successfully generated fully human antibodies against a cancer-related target molecule under their 2004 deal (8/8) Osiris Therapeutics Inc.* JCR Pharmaceuticals Co. Ltd. (Japan) ND Milestone payment A milestone was met in an August 2003 deal that granted JCR rights in Japan to a stem cell drug for graft-vs.-host disease (8/4) Pharmasset Inc.* Incyte Corp. (INCY) ND Milestone payment Triggered when Reverset exceeded the goal in reducing HIV viral load in a trial called Study 203 (8/23) Merck & Co. Inc. AUGUST BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 129 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) 7TM Pharma A/S* (Denmark) Johnson & Johnson Development Corp. ND Equity investment 7TM and J&J are collaborating on development of oral compounds for treating asthma and allergic diseases; terms of the investment were not disclosed (8/18) TopoTarget A/S (Denmark; CSE:TOPO) CuraGen Corp. (CRGN) $4.8 Milestone payment The milestone was paid for extending a Phase II trial of the histone deacetylase inhibitor PXD10 1 in multiple myeloma to the U.S. (8/9) $4 Milestone payment Triggered by FDA approval of Fortical calcitonin-salmon nasal spray for treating postmenopausal osteoporosis (8/15) ND Milestone payment Triggered by Adolor’s initiation of a Phase II trial of a sterile lidocaine patch trademarked by EpiCept as LidoPAIN SP (9/26) Indevus Esprit Pharma Pharmaceuticals Inc. Inc. (IDEV) $10 Milestone payment Triggered by initiation of the Phase III program for Sanctura XR in patients with overactive bladder (9/8) TransTech Pharma Inc.* Novo Nordisk A/S (Denmark) ND Milestone payment Triggered by progress made with a drug candidate in their collaboration using TransTech’s small-molecule discovery technology (9/22) Merck & Co. Inc. ND Milestone payment Triggered by Abmaxis’ optimization of an undisclosed Merck human monoclonal antibody (10/18) Acadia Allergan Pharmaceuticals Inc. Inc. (ACAD) ND Milestone payment Triggered by the start of an initial exploratory Phase II trial in their neuropathic pain program (10/3) Acusphere Inc. (ACUS) Nycomed Danmark A/S (Denmark) $0.15 Milestone payment The payment is the first of what could be $58M in milestone-based license fees for progress in development of AI-700, an ultrasound agent (10/24) CepTor Corp. (OTC BB:CEPO) JCR Pharmaceuticals Co. Ltd. (Japan) $1.5 Milestone payment Triggered by the filing of an investigational new drug application for Myodur (C-101) in muscular dystrophy; $1M of the payment was in equity and $500,000 cash (10/20) Unigene Upsher-Smith Laboratories Laboratories Inc. (OTC BB:UGNE) Inc. SEPTEMBER EpiCept Corp.* Adolor Corp. OCTOBER Abmaxis Inc.* 130 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Codexis Inc.* Pfizer Inc. ND Milestone payment Triggered by the second technical milestone in deal to generate biocatalysts for the manufacture of Pfizer’s products (10/4) Discovery Partners International Inc. (DPII) Allergan Inc. ND Milestone payments Triggered by identification of lead compounds from their multitarget drug discovery collaboration; the therapeutic focus was not disclosed (10/31) Flamel Technologies SA (France; FLML) GlaxoSmithKline plc (UK) $2 Milestone payment Triggered by successful Phase III trial results on a controlled-release formulation of an already marketed GSK drug using Flamel’s Micropump technology (10/26) 454 Life Sciences (majority owned By CuraGen Corp.; CRGN) Roche Diagnostics (Switzerland) $7.5 Milestone payment Triggered by the commercial launch by Roche Applied Science of the Genome Sequencer 20 System and reagents from 454 (10/7) Novexel* (France) Sanofi-Aventis Group (France) ND Milestone payment Triggered by the start of a Phase I trial of NXL 103, an oral antibiotic for which Sanofi holds a development option (10/3) Orexo AB* (Sweden) Endo Pharmaceuticals Inc. $6.5 Milestone payment Triggered by successful completion of a dosefinding trial of Rapinyl (OX 20) for managing breakthrough cancer pain (10/3) Pozen Inc. (POZN) GlaxoSmithKline plc (UK) $20 Milestone payment The milestone was triggered by the FDA’s acceptance for review of the new drug application for the migraine product Trexima (10/1 1) Discovery Partners International Inc. (DPII) Seikagaku Corp. (Japan) ND Milestone payment Triggered by Seikagaku’s advancement of a compound identified by DPI in their collaboration to the next stage of development (1 1/9) Metabolex Inc.* Astellas Pharma Inc. (Japan) ND Milestone payment Triggered by Astellas’ selection of additional validated targets for drug screening and development in their collaboration (1 1/8) Medarex Inc. (MEDX) Bristol-Myers Squibb Co. ND Milestone payment Triggered by advancement into clinical trials of BMS-66513, a fully human antibody that targets CD137 developed using Medarex technology (1 1/15) NOVEMBER BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 131 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Micromet AG * (Germany) MedImmune Inc. (MEDI) ND Milestone payment Triggered by Micromet’s generation of BiTE molecules against a MedImmune oncology target (1 1/21) Neose Technologies Inc. (NTEC) Novo Nordisk A/S (Denmark) ND Milestone payment The payment stems from November 2003 deal to use Neose’s GlycoPEGylation technology to develop next-generation versions of already-marketed therapeutic proteins (1 1/21) Vical Inc. (VICL) Merck & Co. Inc. $1 Milestone payment Triggered by Merck’s initiation of a Phase I trial of a DNA cancer vaccine based on Vical’s DNA gene delivery technology (1 1/8) ND Equity investment SeqWright is making an undisclosed follow-on investment in VisiGen (1 1/2) VisiGen SeqWright Inc. Biotechnologies Inc.* DECEMBER Cerep SA (France; Nouveau Marche:CERF) Bristol-Myers Squibb Co. ND Milestone payment Triggered by entry into Phase I trial of a second LFA-1 antagonist, being developed for immuno-inflamatory disorders (12/14) Critical Therapeutics Inc. (CRTX) MedImmune Inc. (MEDI) $1.25 Milestone payment Triggered by preclinical progress in their deal to develop fully human monoclonal antibodies for rheumatoid arthritis and sepsis (12/8) Cytokinetics Inc. (CYTK) GlaxoSmithKline plc (UK) $0.5 Milestone payment Triggered by GSK’s selection of a small-molecule development candidate, GSK-923295, against a mitotic kinesin target from their 2001 collaboration (12/13) Dyax Corp. (DYAX) Genzyme Corp. (GENZ) $3 Milestone payment Triggered by initiation of a pivotal Phase III trial of Dyax’s DX-88 in patients with hereditary angioedema (12/8) Enanta Shionogi & Co. Pharmaceuticals Ltd. (Japan) Inc.* ND Milestone payment Triggered by the start of Phase II trials in Japan of the antibiotic EDP-420 (EP-013420; S-13420) (12/20) Evotec AG (Germany; FSE:EVT) Takeda Pharmaceutical Co. Ltd. (Japan) ND Milestone payment The payment was triggered by target identification and validation work related to a target in Alzheimer’s disease (12/6) Flamel Technologies SA (France; FLML) GlaxoSmithKline plc (UK) $2 Milestone payment Triggered by GSK’s submission of an NDA on a controlled-release formulation of a marketed GSK drug using Flamel’s Micropumptechnology (12/21) 132 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Milestones And Equity Investments From Corporate Partners (Ongoing Alliances) (Continued) Company (Symbol)# Partner (Country) Amt. (M) Triggering Event Details (Date) Genmab A/S (Denmark; CSE: GEN) F. Hoffmann-La Roche Ltd. (Switzerland) ND Milestone payment Roche filed an IND for a Genmab antibody developed under their deal; it was ninth milestone reached by Genmab in their collaboration (12/13) Lexicon Genetics Inc. (LEXG) Genentech Inc. (NYSE:DNA) $20 Milestone payments Lexicon earned the payments for progress in programs related to Genentech’s Secreted Protein Discovery Initiative and delivery of data on target identification (12/20) Maxygen Inc. (MAXY) F. Hoffmann-La Roche Ltd. (Switzerland) $5 Milestone payment The milestone from their 2003 deal to develop improved interferon alpha protein therapeutics for hepatitis C was triggered by undisclosed progress (12/14) Medivir AB (Sweden; SSE: MVIRB) Tibotec Pharmaceuticals Ltd. (Ireland) €5 ($6) Milestone payment Triggered by progress in preclinical development in their collaboration to develop drugs for treating heaptitis C virus (12/29) Onyx Bayer Pharmaceuticals Pharmaceuticals Inc. (ONXX) Corp. $10 Milestone payment Triggered by FDA approval of their drug Nexavar (sorafenib) for treating advanced renal cell carcinoma (12/20) Perlegen Sciences Inc.* $50 Equity investment The $50M investment gave Pfizer 1 2% of Perlegen; it also agreed to invest up to $25M more in Perlegen’s IPO if the IPO completes in 2006 (12/27) Sunesis Biogen Idec Pharmaceuticals Inc. (BIIB) Inc. (SNSS) $0.5 Milestone payment Triggered by progress relating to the discovery of Raf kinase inhibitors for treating cancer, from their September 2004 deal (12/7) Vernalis plc (UK; VNLS) $1.5 Milestone payment Triggered by Novartis’ selection of a development candidate from the collaboration on the oncology target Hsp90 (12/19) $19.5 Milestone payments Two milestones were triggered: Phase I data from a trial of the cancer agent VX-680 (MK-0457) and from Merck’s selection of a follow-on compound for development (12/7) Pfizer Inc. Novartis AG (Switzerland) Vertex Merck & Co. Inc. Pharmaceuticals Inc. (VRTX) Notes: # Unless otherwise indicated, shares are traded on the Nasdaq exchange. * Private company. Currency conversions are based on exchange rates at the time of the deal. ND = Not disclosed. FSE = Frankfurt Stock Exchange; AIM = Alternative Investment Market; AMEX = American Stock Exchange; ASX = Australian Stock Exchange; CSE = Copenhagen Stock Exchange; FSE = Frankfurt Stock Exchange; LSE = London Stock Exchange; NYSE = New York Stock Exchange; OTC BB: Over-the-Counter Bulletin Board; SSE = Stockholm Stock Exchange; SWX = Swiss Stock Exchange; TSE = Toronto Stock Exchange. 133 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies Company (Symbol) Funding Institution Amount (M) Type Details (Date) Aastrom Biosciences Inc. (ASTM) National Institutes of Health $0.79 Phase II SBIR grant To support development of the AastromReplicell System for large-scale manufacturing of cell-based products (10/18) Aastrom Biosciences Inc. (ASTM) National Institute of Diabetes and Digestive and Kidney Diseases $0.416 Phase II SBIR grant The grant will be used to support use of the company’s tissue repair cells in bone formation and vascularization (8/16) Achillion Pharmaceuticals Inc.* National Institute of Allergy and Infectious Diseases ND Phase I SBIR grant The grant will support Achillion’s program for identifying smallmolecule HIV capsid assembly inhibitors, and to further characterize capsid inhibition as an HIV treatment method (5/2) Acumen Pharmaceutical Inc.* National Institute on Aging ND SBIR grant To develop a diagnostic to test levels of amyloid-beta-derived diffusible ligands from patients with Alzheimer’s disease (8/1 1) Adenosine Therapeutics LLC* Department of Health and Human Services $2 Phase I/II SBIR grant The grant will support completion of Phase I and II trials of ATL146e to prevent cardiac reperfusion injury (7/7) Adenosine Therapeutics LLC* National Institutes of Health $0.14 Phase I SBIR grant The grant will fund the development and testing of A2A antagonists for treating Parkinson’s disease (2/17) AdipoGenix Inc.* National Institute of Diabetes and Digestive and Kidney Diseases ND Phase I SBIR grant For use in a collaboration with ChemDiv Inc. to further progress small molecules that target human fat tissue for treating obesity and Type II diabetes (6/23) Affectis Pharmaceuticals AG* (Germany) German Ministry of Research and Education and the state of Bavaria €2.2 ($2.6) Grants The ministry is providing €1.7M for development of a depression drug that targets a specific ion channel; a Bavaria program is providing €0.5M for discovery of genes involved in depression and anxiety (10/18) 134 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Affectis Pharmaceuticals AG* (Germany) German government €0.75 ($1) Grant The funds will be used to advance the company’s discovery and development programs, particularly its depression program (1/31) Akubio Ltd.* (UK) Army Medical Research Institute of Infectious Diseases $3 Joint development program The parties will use $3M in funding from the U.S. National Institute of Allergy and Infectious Diseases to develop enhanced systems for the detection of bioterrorism agents based on Akubio’s acoustic biosensor technology (5/17) Alchemia Ltd. (Australia; ASX:ACL) Australian government A$7.8 ($6) Pharmaceuticals Partnerships Program grant The grant entitles Alchemia up to A$7.8M over three years for its programs if it meets forecast R&D spending for the period (3/31) Alnylam Pharmaceuticals Inc. (ALNY) Department of Defense ND Funding support The funds will support development of RNAi therapeutics for pandemic influenza (12/14) Alnylam Pharmaceuticals Inc. (ALNY) Michael J. Fox ND Foundation for Parkinson’s Research Grant The grant will support work on the use of small interfering RNAs to silence alpha-synuclein, the overexpression of which has been linked to Parkinson’s disease (8/15) Alnylam Pharmaceuticals Inc. (ALNY) Cystic Fibrosis Foundation Therapeutics Inc. $1.5 Funding award Alnylam will apply RNAi technology to the discovery of short interfering RNAs to restore protein function in CF (3/16) AlphaVax Inc.* National Institute of Allergy and Infectious Diseases $3.3 Grant The funding will be used for preclinical development of a vaccine for smallpox (10/19) AlphaVax Inc.* National Institute of Allergy and Infectious Diseases $6.5 Grant The three-year award will support the preclinical development of an influenza vaccine using the company’s vaccine technology, the AlphaVax replicon vector system (4/18) Altachem Pharma Ltd. (Canada; TSE:AAF) National Research Council (Canada) C$0.445 ($0.371) Industrial Research Assistance Program support The funding will support development of Altachem’s photodynamic therapy for prostate cancer (1/5) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 135 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Altor BioScience Corp.* National Cancer Institute ND Phase I SBIR grant The grant will support development of Altor’s processes for making therapeutic antibodies in transgenic lettuce (7/21) Amarillo Biosciences Inc. (OTC BB:AMAR) National Institutes of Health $0.104 Phase I SBIR grant The grant will be used to further develop a vaccine to combat Helicobacter pylori (5/5) Angel Biotechnology Ltd.* (UK) Undisclosed £275,000 R&D grants ($502,595) Two grants will support Rapid Recombination technology and Angel’s antiviral antibody program (5/24) Argos Therapeutics Inc.* Ontario Cancer Research Network $0.57 Grant McMaster University got the grant to fund a clinical trial of Argos’ RNA-loaded dendritic cell vaccine technology in chronic lymphocytic leukemia (1 1/8) Argos Therapeutics Inc.* Alliance for Lupus Research $1 Grant For development of a therapeutic antibody product for systemic lupus erythematosis based on research conducted at Baylor Institute for Immunology Research (2/2) Ark Therapeutics Group plc* (UK) Employment and €2.19 Economic Develop($2.5) ment Center of Finland Grant Funding will support the company’s investment in GMP manufacturing facility in Kuopio, Finland (1 1/3) Artemis Pharmaceuticals GmbH* (Germany) German government €1.3 ($1.6) Grant The grant will support work from Artemis and RiNA GmbH to develop methods to knock down human disease-related genes in the rat via RNA interference (7/19) Asklepios BioPharmaceutical Inc.* North Carolina Biotechnology Center $0.15 Small Business Research Award The loan will be used to develop a gene therapy treatment for congestive heart failure (3/8) Atom Sciences Inc.* National Institute of Allergy and Infectious Diseases $0.1 Phase I SBIR grant The grant will support development of a diagnostic tool for tuberculosis using a method called Limited Primer Extension (4/21) 136 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Avant Immunotherapeutics Inc. (AVAN) National Institutes of Health $0.374 Subcontract from Harvard Medical School Avant got a portion of the $0.5M Harvard grant to develop a VitriLife formulation of its cholera vaccine CholeraGarde (7/18) Biofactura Inc.* Maryland Technology Development Corp. ND TEDCO investment The funds will support its collaboration with USAMRIID for development of therapeutics for poxviruses (4/21) Biolog Inc.* National Institute of Allergy and Infectious Diseases ND Phase I SBIR grant The grant from the Biodefense Program will be used to develop Phenotype MicroArray technology as a tool in antimicrobial research (3/1) BioPort Corp.* Department of Health and Human Services $122.7 Project BioShield contract The contract calls for BioPort to manufacture 5 million doses of anthrax vaccine for use in the federal stockpile (5/6) BioVisioN AG* (Germany) German Federal €0.56 Ministry of Education ($0.69) and Research BioChancePLUS program grant BioVision will apply it Peptidomics technologies to analyze substrates and products of proteases in vivo (8/4) Bioxel Pharma Inc. (Canada; CDNX:BIP) Natural Sciences and Engineering Research Council of Canada C$0.273 ($0.234) Funding support The funding is to support formulation development of anticancer drugs; it will take the form of a grant, with installments paid upon completion of development milestones (12/16) Blue Heron Biotechnology Inc.* National Human Genome Research Institute ND Phase I SBIR grant The grant funds development of protein bead technology for studying protein function (9/15) Blue Heron Biotechnology Inc.* National Institute of General Medical Science and the NIAID ND Phase I SBIR grant The grant funds development of molecular biological tools to enable research on genes that are difficult to grow in bacteria (9/8) Bolder BioTechnology Inc.* National Institute of General Medical Sciences $0.122 Phase I SBIR grant Bolder will optimize the pharmacological properties of an enzyme, butyrylcholinesterase, which is capable of inactivating toxic nerve agents (10/10) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 137 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Bolder BioTechnology Inc.* National Cancer Institute $0.122 Phase I SBIR grant To evaluate the company’s longacting gamma interferon analogue for treating ovarian cancer in animal models (8/12) Bolder BioTechnology Inc.* National Institute of Allergy and Infectious Diseases $0.99 Phase I SBIR grant The grant will support work to improve the properties of gamma interferon for stimulating the immune system to fight infections (5/18) Bolder BioTechnology Inc.* National Institute of Arthritis and Musculoskeletal and Skin Diseases $0.1 Phase I SBIR grant The grant supports work to optimize a human protein to enhance its ability to inhibit formation of new blood vessels; the target is rheumatoid arthritis (1/20) Bolder BioTechnology Inc.* National Institute of Diabetes and Digestive and Kidney Diseases $0.5 Phase I SBIR grant The two-year grant will be used on preclinical work for an erythropoiesis-stimulating protein, which is being developed for anemia (1/13) Bolder BioTechnology Inc.* National Institute of Allergy and Infectious Diseases $0.303 Phase I SBIR grant The grant will be used on preclinical work for the firm’s longacting growth hormone product (1/12) Callisto Pharmaceuticals Inc. (AMEX:KAL) National Institute of Allergy and Infectious Diseases $0.89 Biodefense Partnerships grant To develop a monoclonal antibody and vaccine against bacterial superantigen toxins, which have potential for use as bioweapons (4/1) Cambria Biosciences LLC* National Institutes of Health $0.7 Three Phase I SBIR grants Grants from the National Institute of Neurological Disorders and Stroke and the National Institute of Environmental Health Sciences (NINDS) will support development of disease models for stroke, and an NINDS grant will support work to elucidate the molecular sites of action of riluzole in treating amyotrophic lateral sclerosis (2/1 1) 138 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Cambridge Biostability Ltd.* (UK) National Institute of Allergy and Infectious Diseases $3.5 Grant The company is getting funding from a grant awarded to DVC LLC for development of stable multivalent vaccine formulations to provide protection against botulism (2/28) Carrington Laboratories Inc. (CARN) National Institute of Allergy and Infectious Diseases $0.463 Biodefense grant Carrington subsidiary DelSite Biotechnologies Inc. will use the second year of funding to continue evaluating its GelVac system to nasally deliver antigens associated with common infectious diseases (4/14) CellCentric Ltd.* (UK) National Endowment for Science, Technology and the Arts (UK) £0.15 ($0.27) Funding support The funding will be used to increase discovery capacity for epigenetic-related cancer targets and therapeutics (9/5) Cellzome Inc.* and Santhera Pharmaceuticals AG* (Switzerland) German Ministry of Research and Education €2.2 ($2.6) Grants Cellzome and Santhera’s Graffinity will use funding to support discovery of treatments for immune system disorders (10/12) Ceragenix Pharmaceuticals Inc. (OTC BB:CGXP) National Institutes of Health $1.2 Grant To study the role of the skin’s barrier function as it relates to eczema vaccinatum, a potentially fatal complication of smallpox vaccination (8/17) Cerus Corp. (CERS) National Institute of Allergy and Infectious Diseases $2.8 Contract Cerus is getting $2.8M as part of a consortium to develop a prophylactic vaccine against the bacterium that causes tularemia; the total contract is $23M (10/5) ChemDiv Inc.* National Institutes of Health $9 Grant ChemDiv and research teams in New Mexico got the three-year grant to develop the New Mexico Molecular Library Screening Center (7/1 1) Chiron Corp. (CHIR) Department of Health and Human Services $62.5 Contract Chiron won a contract to supply the U.S. government with prepandemic influenza vaccine for a stockpile to protect against the H5N1 avian influenza virus strain (10/27) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 139 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) ChondroGene Ltd. (Canada; CDNX:CDG) National Research Council (Canada) ND Industrial Research Assistance Program funding The funding will support development of a blood-based molecular diagnostic assay for osteoarthritis (3/16) CODA Genomics Inc.* National Institute of Allergy and Infectious Diseases $0.5 STTR grant CODA and the University of California at Irvine will use the grant to expand synthetic gene assembly and protein expression technologies (9/1) CollaGenex Pharmaceuticals Inc. (CGPI) National Institutes of Health $0.962 Grant The two-year grant will support research into the anti-inflammatory effects of incyclinide (Col-3), a compound currently in Phase II trials for treating acne (1 1/9) CombiMatrix Group (CBMX) U.S. Air Force $0.338 Contract One-year contract to develop and produce microarrays to detect pathogens that cause upper respiratory infections and pathogens that infect wounds (9/28) CombinatoRx Inc.* National Institute of Allergy and Infectious Diseases $4.4 Cooperative research grant CombinatoRx will get up to $4.4M to discover combinations of approved small-molecule drugs that block the adverse effects of anthrax lethal toxin; it would own resulting products (4/13) Copernicus Therapeutics Inc.* Cystic Fibrosis Foundation Therapeutics Inc. $0.75 Extension of award The award extension will support Phase II advancement of Copernicus’ nonviral nanoparticle gene therapy for CF; the total award is $1.03M (1/20) Crucell NV (the Netherlands; CRXL) Dutch Ministry of Economic Affairs €2 ($2.4) Senter grant The grant supports an effort to apply MAbstract technology to the discovery of antibodies to assist in the development of drugs against antibiotic-resistant bacteria (9/16) Crucell NV (the Netherlands; CRXL) and Harvard Medical School National Institutes of Health $19.2 Grant The funds will support development of adenovirus vector-based vaccines against HIV/AIDS; about $8M is earmarked for development of Crucell’s AdVac technology (8/1) 140 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Crucell NV (the Netherlands; CRXL) National Institute of Allergy and Infectious Diseases $27.6 Manufacturing contract Crucell will manufacture up to 10 batches of clinical material of the PER.C6-based Ebola vaccine for use in Phase I and early Phase II trials (4/14) Crucell NV (the Netherlands; CRXL) Department of Health and Human Services ND Subcontract award Crucell partner Sanofi Pasteur was awarded a $97M contract from HHS to develop a PER.C6based cell-culture influenza vaccine; Crucell is a subcontractor for the work (4/1) CureLab Inc.* National Institutes of Health ND Phase I SBIR grant The grant will support development of a vaccine against the influenza virus; CureLab said funding is expected to eventually total $7M (8/1) Cyprotex plc (UK; LSE:CRX) Department of Trade & Industry (UK) ND Grant The grant will be used to extend Cyprotex’s predictive technologies used in the invention of new drugs (10/26) DCV Technologies Inc.* National Cancer Institute $0.1 Grant For preclinical research on the company’s dendritic-cell immunotherapy in ovarian cancer (6/14) Deltagen Inc. (PK:DGENQ) National Institutes of Health ND Contract award Deltagen will provide knockout mice to NIH and its partners (10/5) DermTech International* University of California $0.138 Discovery grant For research on a product for the non-invasive diagnosis of early stage melanoma (6/23) Diatos NV* (Belgium) Flemish Institute for Science and Technology €0.65 ($0.87) Grant The money will be used to apply Tumor-Selective Prodrug technology to development of cytokine prodrugs with antitumor activity (2/16) Dimerix Bioscience Pty. Ltd.* (Australia) AusIndustry (Australia) A$0.2 ($0.15) Commercial Ready grant The grant will support development of a new class of drugs targeting G protein-coupled receptors (5/1 1) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 141 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Diversa Corp. (DVSA) Department of Defense $4.8 Biodefense contracts A $2.5M contract will support the second year of Diversa’s “Rapid Antibody-Based Biological Countermeasures” program; a $2.3M contract funds the second year of its “Enzyme-Based Active Decontamination” of chemical and biological agents program (3/9) Domantis Ltd.* (UK) European Union N/A Grant Domantis and 13 others got a €9M grant as part of the Bloodomics Consortium, which is focused on finding targets and drugs for cardiovascular diseases (1/24) DVC LLC Department (unit of Computer of Defense Sciences Corp.; NYSE:CSC) $19.6 Contract award DVC will lead a collaboration that includes Baxter Healthcare Corp. to develop plasma-derived human butyrylcholinesterase for protecting against the toxic effects of certain chemical warfare agents (4/13) Dynavax Technologies Corp. (DVAX) Alliance for Lupus Research $0.5 Grant Dynavax will explore new treatment approaches for lupus using its immunoregulatory sequences technology (1/10) Edison Pharmaceuticals Inc.* Friedreich’s Ataxia Research Alliance $3 Grant The grant will be used to advance development of EPIA000 1 for treating Friedreich’s ataxia (1 1/8) Edison Pharmaceuticals Inc.* Friedreich’s Ataxia Research Alliance $0.3 Grant Funding will support work at Edison in Friedreich’s ataxia (10/25) Edison Pharmaceuticals Inc.* Muscular Dystrophy Foundation ND Funding support Funding will support work at Edison in Friedreich’s ataxia (10/20) Elusys Therapeutics Inc.* National Institute of Allergy and Infectious Diseases and the Department of Defense $5.4 Funding awards The funding will support development of Anthim, an antibody therapeutic for preventing and treating anthrax infection; $4.4M came from the NIAID and $1M from the DOD (8/3) 142 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Encore Pharmaceuticals Inc.* National Institute on Aging $0.75 Phase II SBIR grant To support work with the Oklahoma Medical Research Foundation on a drug candidate for amyotrophic lateral sclerosis and Huntington’s disease (8/9) EntreMed Inc. (ENMD) Susan G. Komen Breast Cancer Foundation ND Grant Duke University got the grant to test EntreMed’s Panzem (2ME2) in combination therapies for metastatic breast cancer (6/29) Epitome Biosystems* National Science Foundation $0.5 Phase II SBIR grant Epitome will develop an antibody array that will integrate the measurement of phosphoproteins from three cell-signaling pathways into a single assay system (10/17) EpiVax Inc.* National Institutes of Health $0.6 Phase I SBIR grant The grant will be used to develop a genome-derived, epitopedriven Helicobacter pylori vaccine (4/27) ESA Biosciences Inc. (subsidiary of Magellan Biosciences Inc.*) National Institutes of Health ND Roadmap Initiative grant ESA will extend and integrate electrochemical and mass spectrometric technologies to facilitate a range of metabolomics studies (3/24) FASgen Inc.* National Institutes of Health $2.1 SBIR grant Funds will support completion of preclinical work on small-molecule drugs for obesity and related metabolic disorders (10/1 7) FASgen Inc.* National Institutes of Health $0.5 Grant The grant will support completion of final preclinical work for the company’s FAS20013 tuberculosis candidate (5/13) 4SC AG* (Germany) Federal Ministry of Education and Research (Germany) €2.9 ($3.65) BioChancePLUS program grant The 2.5-year funding will support development of drug candidates for treating autoimmune diseases particularly multiple sclerosis (5/10) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 143 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Galapagos NV (Belgium; Euronext: GLPG) and Amsterdam Molecular Therapeutics BV* (the Netherlands) Dutch government €2 ($2.4) Senter grant The companies will work with the Netherlands Institute for Brain Research and the Vrije Universiteit Amsterdam to develop treatments for acute spinal cord and peripheral nerve damage (9/14) Galapagos NV (Belgium; Euronext: GLPG) Dutch Ministry of Economic Affairs €1.2 ($1.5) Grant To support a drug discovery program in arthritis that includes ZoBio BV, Pyxis Discovery BV and Leiden University (8/10) Galenea Corp.* National Institute of Allergy and Infectious Diseases ND Phase I SBIR grant For further development of the company’s siRNA product G00101 against multiple influenza strains, including avian flu (1 1/17) Genaera Corp. (GENR) Cystic Fibrosis Foundation Therapeutics Inc. $2.35 Therapeutics Development Award CFFT is supporting a pivotal Phase II trial in Ireland of Lomucin in CF patients through milestone-driven matching funds (4/18) GeneGo Inc.* National Institute of General Medical Science ND Phase II SBIR grant To further develop the computational tool MetaDrug to improve the prediction of ADME and toxicology properties of novel smallmolecule compounds (8/3) GeneGo Inc.* Department of Defense ND SBIR grant The grant will support development of a systems biology suite of tools for visualization and analysis of proteomic data (6/27) GeneGo Inc.* National Institute of General Medical Science ND Phase I SBIR grant The grant will support development of methodologies to reconstruct functional networks affected in common human diseases (6/13) GeneGo Inc.* National Institute of Environmental Health Sciences ND Phase I SBIR grant The grant is for the elucidation and analysis of signaling and metabolic networks implicated in cellular response to drugs and toxins (5/24) 144 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) GeneGo Inc.* National Cancer Institute ND Phase I SBIR grant GeneGo will use its systems biology platform to elucidate and analyze cellular networks implicated in breast cancer (2/7) Genencor International Inc. (unit of Danisco A/S; Denmark) Department of Defense $2 Contract Genencor will work with the U.S. Army Edgewood Chemical and Biological Center to develop an enzyme-based decontamination solution targeting chemical and biological warfare agents (10/31) Genencor International (unit of Daniso A/S; Denmark) Defense Advanced Research Projects Agency ND Grant To develop a process for the rapid manufacture of emergency pharmaceuticals to defend against biological agents (8/29) Gene Network Sciences* National Heart, Lung and Blood Institute $0.138 Phase I SBIR grant The grant will be used to further the company’s efforts in cardiac modeling and in silico safety testing (7/26) Gene Network Sciences* National Heart, Lung and Blood Institute $0.2 Phase I SBIR grants Two six-month, $100,000 grants will support development of a simulation platform and software for cardiac modeling (2/2) Genomic Profiling Systems Inc.* National Institute of Allergy and Infectious Diseases $4.1 Phase II SBIR grant Three-year grant to develop a testing platform for rapid and ultra-sensitive diagnosis of anthrax (8/12) GenPat77* (Germany) German Ministry of Research and Education ND BioChancePLUS program grant The grant will support development of its immunomodulator program in inflammatory bowel disease (10/1 1) GenVec Inc. (GNVC) National Institute of Allergy and Infectious Diseases $9.9 Subcontract award from SAIC-Frederick contract GenVec got increased funding for its HIV vaccine development work with the Vaccine Research Center of the NIAID (10/5) GenVec Inc. (GNVC) Department of Defense $1.6 Contract award GenVec will manufacture an adenovector-based malaria vaccine candidate for the U.S. Naval Medical Research Center (2/20) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 145 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) GenVec Inc. (GNVC) National Institute of Allergy and Infectious Diseases $10 Extension of subcontract The institute’s Vaccine Research Center will use GenVec’s technologies in the development of an HIV vaccine (1/12) GPC Biotech AG (Germany; GPCB) and Ingenium Pharmaceuticals AG* (Germany) German Ministry for Education and Research €2.2 ($2.8) BioChancePLUS program grant The funds will support a program to establish proof of concept for the activity of specific kinase inhibitors in animal models covering several disease areas; each company will get €1.1M (4/26) Greystone Medical Group* Department of Defense $0.75 STTR grant Greystone and the University of Tennessee Health Science Center will use the money to complete preclinical research on a drug to treat hemorrhagic shock (2/24) Hana Biosciences Inc. (OTC BB:HNAB) National Institutes of Health $0.159 SBIR grant The grant supports preclinical studies of Talotrexin (PT-523) as part of chemotherapy regimens (8/8) Human Genome Sciences Inc. (HGSI) Department of Health and Human Services $1.8 Contract award HGS first will supply the ABthrax anthrax monoclonal antibody for preclinical testing; that could lead to an order within a year for up to 100,000 doses for the national stockpile; $1.8M was awarded for the first stage (10/3) Hyalose LLC* Oklahoma Center for Advancement of Science and Technology $0.227 Grant The grant will support development of hyaluronan-assisted targeting systems for drug delivery (7/18) Iceland Genomics Corp.* (Iceland) European Union ND 6th Framework Program grant A consortium including IGC, Bioinformatics ApS, University of Oxford and Radboud University will study the inherited risk of breast and prostate cancers (12/19) Icon Genetics AG* (Germany) Bavarian Research Foundation (Germany) ND Funding support The funding supports a collaboration with Research Centre Freising and the University of Munich to develop switches for controlling expression of transgenes in plant chloroplasts (4/1 1) 146 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Iconix Pharmaceuticals Inc.* Environmental Protection Agency ND Contract award Iconix will use its chemogenomics platform to predict the toxicity of potentially hazardous chemicals of interest to the EPA (1/6) Icoria Inc. (OTC BB:ICOR) National Institute on Alcohol Abuse $0.8 Phase II SBIR grant Icoria will apply metabolomics and gene expression analysis in the study of alcohol-related diseases, including liver and brain injury (10/20) Icoria Inc. (OTC BB:ICOR) Environmental Protection Agency and Duke University ND Contracts Icoria will provide microarray expression services related to environmental toxicants in each deal (9/8) Icoria Inc. (OTC BB:ICOR) National Institute of Environmental Health Sciences $1.2 Phase II SBIR contract Funding will be used to discover biomarkers for drug-induced liver injury (8/29) ImaRx Therapeutics Inc.* National Heart, Lung and Blood Institute $1.1 Phase II SBIR grant The grant supports development of targeted nanobubbles that can be used with ultrasound for NanoInvasive treatment of vascular clots (8/2) Immunicon Corp. (IMMC) and the Fox Chase Cancer Center National Institutes of Health $0.587 STTR grant To fund development of a strategy to monitor the effectiveness of cancer drugs in trials by examining a patient’s blood for tumor cells and related materials (6/13) Indevus Pharmaceuticals Inc. (IDEV) UK government and the Medical Research Council £26M ($49) Funding support For a Phase III trial in Africa of PRO 2000, the company’s microbicide being developed to prevent HIV infection (4/6) InfleXion Therapeutics LLC* National Institute on Drug Abuse $3 Grant The grant will support clinical trials of an antibody treatment for addiction to phencyclidine, or PCP (1/27) Inimex Pharmaceuticals Inc.* (Canada) Bill and Melinda Gates Foundation and others $8.7 Grand Challenges in Global Health grant Inimex is part of a consortium working to boost innate immunity to treat infectious diseases; the effort is led by the University of British Columbia (7/7) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 147 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Inovio Biomedical Corp. (AMEX:INO) Department of Defense $1 Defense appropriation For development of its gene delivery electroporation technology for use in vaccines against infectious diseases (9/13) IntegraGen SA* (France) European Union €12.5 ($16) Funding support IntegraGen is part of the EuroHear consortium that includes 25 institutions in Europe; they will carry out research in hearing impairments (4/17) IntegraGen SA* (France) European Union N/A 6th Framework Program grant IntegraGen is one of 30 groups participating in the DiOgenes (Diet, Obesity and Genes) project that together were awarded €14.5M; IntegraGen will work on genetic aspects of the project (1/25) Integrated Nano-Technologies LLC* National Science Foundation $0.5 SBIR grant The two-year grant will support further R&D of its DNA detection technology for detecting the presence of biological agents (3/28) Intercell AG (Austria; VSE:ICLL) European Union €1.4 ($1.8) 6th Framework Program grant Intercell will work with five other EU institutions and firms to develop a novel vaccine against Lyme borreliosis (5/23) Iomai Corp.* National Institute of Allergy and Infectious Diseases $2.9 Grant The grant will support development of a skin patch designed to improve responses to influenza vaccination (1/31) Ipsat Therapies* (Finland) Tekes; the Finnish National Technology Agency €3 ($3.6) Funding support The funding will support product development through the proofof-concept stage (6/16) Isis Pharmaceuticals Inc. (ISIS) National Institute of Allergy and Infectious Diseases $4.9 Contract award The Ibis division of Isis will get up to $4.9M for continued development of its TIGER biosensor system for diagnosing infectious diseases and identifying and controlling hospital-associated infections (8/2) 148 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Isis Pharmaceuticals Inc. (ISIS) U.S. government agencies $1.1 Subcontract from Science Applications International Corp. The Ibis division of Isis was awarded the contract, details of which were not disclosed (7/28) Isis Pharmaceuticals Inc. (ISIS) Department of Homeland Security and other U.S. agencies $5 Subcontracts from Science Applications International Corp. The Ibis division of Isis will continue advancing development of the TIGER biosensor system for identifying infectious organisms (7/21) Isis Pharmaceuticals Inc. (ISIS) Department of Homeland Security $1.5 Contract awards Isis’ Ibis division got two contracts to develop microbial forensics applications of its TIGER (Triangulation Identification for Genetic Evaluation of Risks) biosensor system and to enhance the system’s database (4/18) KineMed Inc.* National Institute of Neurological Disorders and Stroke ND Phase I SBIR grant The funding will be used to develop applications of a KineMarker (kinetic biomarkers) assay for myelin disorders (3/17) Kucera Pharmaceutical Co.* North Carolina Biotechnology Center ND Small Business Research Award The funding will support preclinical studies of cancer and viral programs (3/8) LAB International Inc. (Canada; TSE:LAB) National Technology Agency of Finland €1.55 ($1.8) Funding support LAB’s subsidiary in Finland, LAB Pharma, got funding to support product development; the money includes grants and loans (10/20) Lentigen Corp. Maryland’s Department of Business and Economic Development ND Challenge Investment Program funding The funding will support development of the company’s lentiviral technology (12/13) Lexicon Genetics Inc. (LEXG) National Institutes of Health $4.9 Contract Three-year deal under which Lexicon will provide knockout mouse lines and related data for use in NIH’s Knockout Mouse Project (10/5) Lexicon Genetics Inc. (LEXG) The Texas Enterprise Fund $35 Contract award Lexicon will create a knockout mouse embryonic stem cell library containing 350,000 cell lines for the Texas Institute for Genomic Medicine (7/15) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 149 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) LigoCyte Pharmaceuticals* National Institutes of Health $4.6 Challenge grant The grant will support preclinical advancement of an intranasal vaccine against anthrax (10/3) Maxygen Inc. (MAXY) National Institutes of Health $12 Grants One grant will support use of the MolecularBreeding directed evolution platform to generate antigens capable of inducing antibody responses to multiple HIV strains; a Phase I SBIR grant also supports HIV research (10/20) Maxygen Inc. (MAXY) Department of Defense $2.4 Contract The funding supports development of a high-throughput vaccine screening platform (10/20) Medicure Inc. (Canada; TSE:MPH) and the universities of Manitoba and Ottawa National Sciences and Engineering Research Council of Canada ND Collaborative Research and Development grant The grant will support development of drugs to reduce verylow-density lipoproteins (6/27) Meditech Research Ltd. (Australia; ASX:MTR) Australian government A$2.98 ($2.3) Commercial Ready Grant Three-year grant will support development of HyCAMP, a drug in Phase II trials for cancer (8/24) MedPharm Ltd.* (UK) UK Biotechnology and Biological Sciences Research Council ND Grant The grant will support development of a topical system for delivering drugs to the nails for treating the fungal infection onchomyosis (4/14) Meridian Bioscience Inc. (VIVO) National Institute of Allergy and Infectious Diseases ND Contract award Meridian subsidiary Viral Antigens will manufacture certain research biologicals for the NIAID’s Biodefense and Emerging Infections Resources program (2/9) Metabolon Inc.* Centers for Disease Control and Prevention ND Contract Metabolon will analyze blood samples to identify disease biomarkers for multiple sclerosis (10/26) Metabolon Inc.* National Institute of Mental Health ND Contract award To identify biomarkers occurring in women affected by premenstrual dysphoric disorder (6/16) 150 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Metabolon Inc.* National Institute of Environmental Health Sciences ND SBIR grant Metabolon will use its metabolomics platform to test plasma samples from amyotrophic lateral sclerosis patients to identify biomarkers for ALS (4/12) MicroIslet Inc. (AMEX:MII) National Institutes of Health $1.7 Phase II SBIR grant The three-year award will be used to further develop its islet cell transplantation technology for treating diabetes (10/5) Microscience plc* (UK) Wellcome Trust (UK) £1.95 ($3.65) Strategic Translation Award The award will be used to advance clinical development in Southeast Asia of its drinkable typhoid vaccine program (3/22) Migenix Inc. (Canada; TSE:MGI) Canadian government C$9.3 ($7.4) Technology Partnerships Canada investment TPC will invest up to C$9.3M for development related to MX-2401, a lipopeptide in preclinical development for treating bacterial infections (4/1) MNLpharma Ltd.* (UK) Welsh Development Agency £0.709 ($1.2) SMARTCymru program grant Grant will go toward development of the immune modulator MNLP 462a as a cancer agent (1 1/21) Morphotek Inc.* Defense Advanced Research Projects Agency $6.3 Challenge grant To apply its morphogenics technology to develop cell lines suitable for the scaleable manufacturing of biologic-based antibiowarfare therapies (9/15) Morphotek Inc.* National Cancer Institute ND Grant The grant will support research to generate antibodies with enhanced antibody-dependent cellular cytotoxicity; the award was from the NCI’s Network for Translational Research in Optical Imaging Consortium (1/31) MultiCell Technologies Inc. (OTC BB:MCET) National Institute of Allergy and Infectious Diseases ND Grant The grant will support a pilot trial using its immunoglobulin therapeutic for treating Type I diabetes (9/14) MultiCell Technologies Inc. (OTC BB:MCET) National Institutes of Health ND SBIR grant To create BioFactories that express a serine protease inhibitor that may be useful for treating sepsis (8/30) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 151 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Nabi Biopharmaceuticals (NABI) National Institute on Drug Abuse $4.1 Grant The grant will help fund development of NicVAX, a vaccine being developed to treat nicotine addiction and prevent smoking relapse (9/12) Nanogen Inc. (NGEN) National Institute of Allergy and Infectious Diseases $2.5 Grant The five-year grant is for development of a prototype integrated diagnostic system for identifying agents that cause sepsis and community-acquired pneumonia (8/1) Neotropix Inc.* Pennsylvania Dept. of Community and Economic Development $0.05 Opportunity grant The grant will help support research and development at Neotropix (9/28) Neurion Pharmaceuticals Inc.* National Institute of Mental Health $0.5 Phase I SBIR grant The grant will support development of drugs to treat anxiety focused on a GABA-A receptor subtype (6/2) Neurome Inc.* National Institutes of Health and the Bill and Melinda Gates Foundation $3.9 Grand Challenges in Global Health grant Three-year program to develop a needle-free vaccine delivery system that will enable administration in any field setting (6/30) Neurome Inc.* National Institutes of Health ND Phase I SBIR grant To develop and validate software to accelerate the graphical delineation of brain regions on digital images used to produce 3-D digital brain atlases (6/7) NexBio Inc.* National Institute of Allergy and Infectious Diseases $6 Phase II SBIR grant For further testing of the company’s influenza candidate Fludase (DAS181), which is nearing clinical trials (8/8) Novavax Inc. (NVAX) National Institutes of Health $1.07 Grant Three-year funding will support development of a severe acute respiratory syndrome vaccine using its Virus-Like Particle technology (2/4) 152 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Onyvax Ltd.* (UK) European Union €4.2 ($5.6) 6th Framework Program grant Onyvax is part of a consortium led by Nottingham Trent University to identify abnormal proteins in ovarian, breast and prostate cancer patients that could indicate if they are likely to benefit from vaccine therapy (2/23) Optimer Pharmaceuticals Inc.* National Institute of Allergy and Infectious Diseases $1.19 Phase II SBIR grant Grant supports development of semi-synthetic macrolides and ketolides as antimicrobial agents (10/17) Optimer Pharmaceuticals Inc.* National Institute of Allergy and Infectious Diseases $0.73 SBIR-Advanced Technology grant The grant will help fund development of OPT-80, which is in a Phase II trial for Clostridium difficile-associated diarrhea (10/17) OriGene Technologies Inc.* National Human Genome Research Institute ND Phase I SBIR grant The grant will be used to validate OriGene’s short-hairpin RNA Kinome collection (6/30) Osel Inc.* National Institute of Allergy and Infectious Diseases ND Grant The multiyear award will support development of an encapsulated MucoCept Lactobacillus strain for preventing bacterial vaginosis and HIV infection (6/9) Oxford BioMedica plc (UK; LSE:OXB) UK Motor Neurone Disease Association £0.35 ($0.63) Research grant The grant will support preclinical evaluation of MoNuDin, a gene therapy treatment for amyotrophic lateral sclerosis (7/25) PamGene International BV* (the Netherlands) Dutch Ministry of Economic Affairs €2 ($2.66) SenterNovem program grant PamGene will develop bioinformatics and systems biology on its PamChip Array platform in conjunction with the University of Rotterdam, the Wilhelmina Kinderziekenhuis and the VTT Technical Research Centre (3/9) PamGene International BV* (the Netherlands) European Union ND 6th Framework Program grant PamGene is part of a consortium to develop diagnostics for mitochondrial disease; others are the University of Maastricht, Radboud University Medical Centre, INSERM, the National Institute of Neurology in Italy and the University of Newcastle-upon-Tyne (3/8) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 153 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Amount (M) Type Details (Date) Pepscan Systems European BV* (the Netherlands), Union Proteomika SL* (Spain) and AlgoNomics NV* (Belgium) €1.2 ($1.6) 6th Framework Program grant The project focuses on developing fully synthetic antibodies to treat pancreatic cancer; also participating are University Medical Centre (the Netherlands), the National Cancer Research Centre (Spain) and the University Louis Pasteur (France) (2/2) Peregrine Pharmaceuticals Inc. (PPHM) Department of Defense $0.58 Grant The University of Texas Southwestern Medical Center got funding to study vascular-targeting antibodies with chemotherapy for treating prostate cancer (1 1/3) Perlegen Sciences Inc.* National Institute of Allergy and Infectious Diseases ND Biodefense Partnership grant Perlegen will analyze the genomes of about 150 Yersinia pestis (which cause the plague) and Y. pseudotuberculosis strains to help distinguish the strains and understand their biology (4/4) Perlegen Sciences Inc.* National Institute of Arthritis and Musculoskeletal and Skin Diseases ND Grant The grant will support a collaboration with the North American Rheumatoid Arthritis Consortium to conduct a high-density wholegenome association study of RA (3/10) Perlegen Sciences Inc.* National Cancer Institute ND Grant Perlegen and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University will study tumor-specific DNA mutations involved in colorectal cancer (2/23) Pharmos Corp. (PARS) Israel Ministry of Industry and Trade $1.3 Office of the Chief Scientist grant The funds will support development of drug candidates from the company’s CB2-selective platform of synthetic cannabinoids (5/2) Phylogica Ltd. (Australia; ASX:PYC) Australian government A$2.27 ($1.7) AusIndustry Commercial Ready grant Grant will support development of Phylomer drug candidates for rheumatoid arthritis (10/24) 154 Funding Institution BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Point Therapeutics Inc. (POTP) Food and Drug Administration $0.6 Orphan Products Development grant The two-year grant will fund the Phase II trial of talabostat in combination with rituximab in advanced chronic lymphocytic leukemia (10/1 1) Polydex Pharmaceuticals Ltd. (Canada; POLXF) and Eastern Virginia Medical School Bill & Melinda Gates Foundation and the U.S. Agency for International Development $24 The foundation gave $12M, and USAID matched the grant for trials of a microbicide to prevent HIV The CONRAD program of EVMS got the grant; the product is partnered with Polydex; Phase III trials will be run in India and four African countries (5/3) Population Genetics Technologies Ltd.* (UK) Wellcome Trust (UK) £1.1 ($2) Grant Wellcome provided funding for the newly formed company to develop a method for obtaining sequence information from thousands of genomes simultaneously (4/20) Predix Pharmaceuticals Holdings Inc.* Cystic Fibrosis Foundation Therapeutics Inc. $12.5 Funding award Predix will get up to $12.5M over three years for programs focused on the defective cystic fibrosis transmembrane conductance regulator protein and discovery of a small-molecule agonist to P2Y to treat the disease (3/16) Proacta Inc.* New Zealand Trade and Enterprise and TechNZ $3.45 Grants Proacta’s New Zealand subsidiary was awarded $2.18M over three years from the Australia New Zealand Biotechnology Partnership Fund to support operations in New Zealand and Australia and was awarded $1.27M from TechNZ to support drug development activities (3/3) Progenics Pharmaceuticals Inc. (PGNX) National Institute of Allergy and Infectious Diseases $10.1 Grant The 3.5-year grant will support research and clinical testing of the HIV drug PRO 140 (9/9) ProlX Pharmaceuticals Corp.* National Cancer Institute $5.6 National Cooperative Drug Discovery Group award ProlX and four research institutions got the five-year award to discover therapies that target cells while minimizing damage to normal, healthy cells (12/7) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 155 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) ProlX Pharmaceuticals Corp.* National Institutes of Health $1.2 SBIR grants ProlX got four grants to support development of the Trx-1 inhibitor PX-12 for cancer and other drugs in the company’s pipeline (8/18) Provid Pharmaceuticals Inc.* National Cancer Institute $0.75 Phase II SBIR contract Provid will use its hypothesisdriven drug discovery chemistry in a two-year collaboration on oncology targets (9/29) PTC Therapeutics Inc.* Muscular Dystrophy Association $1.5 Grant The award will be used to fund development of PTC124 for treating Duchenne’s muscular dystrophy that is due to a nonsense mutation in the dystrophin gene (4/21) PTC Therapeutics Inc.* Cystic Fibrosis Foundation Therapeutics Inc. $1.7 Award The money will support development of PTC124 for treating cystic fibrosis that is due to a nonsense mutation in the cystic fibrosis transmembrane regulator gene (2/21) Reaction Biology Corp.* National Institutes $0.75 of Dental and Craniofacial Research Phase II SBIR grant To apply its DiscoveryDot technology to the high-throughput screening of caspases and other proteases for drug discovery (8/9) Reata Pharmaceuticals Inc.* National Institutes of Health ND Phase I SBIR grant The grant will support development of small-molecule drugs for treating amyotrophic lateral sclerosis (1 1/3) Repligen Corp. (RGEN) Stanley Medical Research Institute $1 Funding support Repligen will get the money under an expanded agreement between the parties for a Phase II trial of uridine in bipolar depression (10/21) Repligen Corp. (RGEN) Stanley Medical Research Institute ND Funding award Repligen will receive funding for a Phase I trial of its formulation of uridine for treating bipolar disorder (3/14) Rexahn Corp.* University of Maryland ND Maryland Industrial Partnership grant The grant will fund a project on ligand screening for novel cancer therapeutics (2/8) 156 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) RxKinetix Inc.* Bill & Melinda Gates Foundation and others ND Grand Challenges in Global Health grant RxKinetix will use the grant to develop room-temperature, stable vaccines for measles and hepatitis B (6/30) Saegis Pharmaceuticals Inc.* The Stanley Medical Research Institute $3.8 Funding support Saegis will get up to $3.8M to continue funding clinical trials of SGS518 as a treatment for the cognitive deficit that occurs in schizophrenia; SMRI provided $2M in 2004 to support Phase I trials (5/12) Sanaria Inc.* National Institute of Allergy and Infectious Diseases $1 Phase II SBIR grant The first year of the grant will support development of its whole-parasite malaria vaccine; another $2M could be awarded over three years (6/20) Sanaria Inc.* U.S. Army $4.09 R&D funding award The funds will support development of the company’s attenuated whole-parasite malaria vaccine (5/2) Saneron CCEL Therapeutics Inc.* National Institutes of Health and the state of Florida $0.26 Phase I STTR grant The grant will support a study to and Florida High Tech evaluate the effects of umbilical Corridor matching grant cord blood transplantation following myocardial infarction in a large animal model (10/1 1) Sangamo BioSciences Inc. (SGMO) Cystic Fibrosis Foundation ND Research funding Sangamo gets two years of funding to generate cell lines for cystic fibrosis research using its zinc finger DNA-binding protein technology (9/29) SeraCare Life Sciences Inc. (SRLS) National Cancer Institute ND Contract expansion SeraCare will provide laboratory support to the NCI for the processing and storage of specimens of people at high risk for cancer; it also will act as a repository for the specimens (10/6) SGX Pharmaceuticals Inc.* National Institute of General Medical Sciences $48.5 Protein Structure Initiative award The NIH award provides five years of renewed funding for the New York Structural GenomiX Research Consortium; SGX will retain about half the funding, with the rest going to participating institutions (7/1) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 157 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) SIGA Technologies Inc. (SIGA) U.S. Army Medical Research and Materiel Command $3.2 Contract One-year contract to use its computational approach to develop countermeasures against smallpox and adenovirus (9/27) SIGA Technologies Inc. (SIGA) National Institutes of Health $1 Funding support The funding will help support preclinical development of SIGA’s oral anti-smallpox drug SIGA246, which is being developed with Saint Louis University (9/20) SIGA Technologies Inc. (SIGA) and TransTech Pharma Inc.* National Institutes of Health $2.7 Challenge grant The companies will use the funds in development of protease inhibitors to treat orthopoxvirus infections, such as smallpox and monkeypox (2/15) Sinovac Biotech Ltd. (China; AMEX:SVA) China Ministry of Science and Technology RMB7 ($0.87) Funding support The funds will support preclinical trials of Sinovac’s Panflu pandemic flu vaccine (12/9) SIRS-Lab GmbH* (Germany) European Union ND 6th Framework Program grant SIRS-Lab is the only non-academic member of the GenOSept project, which got funding to investigate the genetics of sepsis and septic shock (5/24) Solbec Pharmaceuticals Ltd. (Australia; ASX:SBP) Australian Industry Department A$2.26 ($1.66) AusIndustry Commercial Ready grant The funds are expected to cover half the cost of the upcoming Phase II trial of the cancer drug Coramsine (12/20) Solbec Pharmaceuticals Ltd. (Australia; ASX:SBP) Western Australia Department of Industry and Resources A$0.023 ($0.017) Grant The grant will be used to help secure funding for further trials of the company’s cancer drug Coramsine (1 1/18) Solbec Pharmaceuticals (Australia; ASX:SBP) Edith Cowen University (Australia) ND Industry collaboration grant To identify a specific melanoma gene that may allow for development of a diagnostic test (9/2) SomaGenics Inc.* National Institute of Allergy and Infectious Diseases $0.315 Grant For development of siRNA libraries for antiviral discovery (4/1) 158 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) SRI International* National Institute of General Medical Sciences ND Continued grant The unit of the National Institutes of Health has continued a grant to support the modeling of complex mammalian signaling networks based on signaling of the epidermal growth factor receptor using SRI’s Pathway Logic analysis software (5/23) Starpharma Holdings Ltd. (Australia; ASX:SPL) National Institute of Allergy and Infectious Diseases $20.3 Development funding The funding will support development of the vaginal microbicide VivaGel through to the start of large-scale efficacy trials (10/3) Stem Cell Sciences Ltd * (UK) UK government £1.2 ($2.3) DTI Technology Program funding SCS is coordinating a consortium in stem cells that will develop high-throughput cell screening for discovery of regenerative medicines; also participating are the Institute for Stem Cell Research, University College London Biochemical Engineering, GE Biosciences, Global Research Centre and the Insight Faraday Partnership (1/31) Targeted Genetics Corp. (TGEN) National Institute of Allergy and Infectious Diseases $18 Subcontract award Targeted Genetics could receive up to $18M of a $21.75M contract over three years for further development of adeno-associated virus-based vaccines against HIV; two research hospitals also are participating in the award (1 1/28) Thromgen Inc.* National Heart, Lung and Blood Institute $1.49 STTR Competing Continuation grant The grant will fund continued preclinical development of Thrombostatin for preventing blood clots following balloon angioplasty procedures (7/18) To-BBB BV* (the Netherlands) Sanfilippo Syndrome Medical Research Center $0.1 Grant The grant supports a preclinical program on targeting sulphamidase to the brain for treating neurological disorders (10/20) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 159 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Tripos Inc. (TRPS) European Union €0.875 ($1.1) 6th Framework Program grant The grant will pay for seven research fellows from Europe to work at Tripos’ UK unit for 18 months each over four years (6/7) Tripos Inc.* (TRPS) National Institutes of Health $0.86 Phase II SBIR grant The two-year grant will fund creation of a a full-scale library design system based on topomer technology (3/14) United Biomedical Inc.* National Institutes of Health $17 Contract award The contract is expected to cover the full cost of the development and manufacture of a therapeutic vaccine for AIDS (7/5) U.S Genomics Inc.* Department of Homeland Security $16.8 Phase II Advanced Research Project Agency contract U.S. Genomics will complete prototype development of its system for detecting and identifying airborne pathogens using its DNA mapping technology (1 1/30) U.S. Genomics Inc.* National Science Foundation $0.5 Phase II-B SBIR grant The grant will support development of a platform that uses the company’s DNA analysis and genomic mapping technologies (10/5) Vala Sciences* National Institutes of Health ND Two SBIR grants One grant will support assay development and the other, cell image-based software analysis development (2/16) Various companies National Institute of Allergy and Infectious Diseases $27 Project BioShield grants and contract awards Grants went to Apath LLC to develop drugs for Ebola infection; NovoBiotic Pharmaceuticals LLC to develop drugs against anthrax; Nanotherapeutics Inc. to develop single-dose disposable inhalers of two antibiotics; MaxThera Inc. to identify agents against bioterror pathogens; and Veritas Inc. to develop tests used to screen drugs that inhibit the botulinum neurotoxin; contracts went to XOMA LLC to develop and produce antibodies against botulinum toxin type A; and DVC Dynport LLC to produce a vaccine against botulinum toxin type E (5/9) 160 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) Velcura Therapeutics Inc.* National Institute on Aging $1.3 Phase II SBIR grant The grant is for proteomics-based drug discovery in human osteoblasts, for discovery of drugs that stimulate bone formation (7/12) Vesta Therapeutics Inc.* National Institute of Diabetes and Digestive and Kidney Diseases ND Phase I SBIR grant The grant will support exploration of using adipose-derived adult stem cells as a therapeutic modality in liver disease (6/16) Vical Inc. (VICL) Defense Advanced Research Projects Agency $0.5 Department of Defense award The award will fund feasibility studies for a new approach to rapidly manufacture large quantities of DNA vaccines (9/22) Vical Inc. (VICL) National Institute of Allergy and Infectious Diseases $2.9 Challenge grant Grant of up to $2.9M will be used to support development of a DNA vaccine against naturally emerging or weaponized strains of avian influenza (9/15) Vical Inc. (VICL) National Institute of Allergy and Infectious Diseases $12.1 Subcontract award from SAIC-Frederick Inc. Vical will provide multiple clinical lots of DNA vaccines against HIV for the Vaccine Research Center of the NIAID under the subcontract (6/16) Vical Inc. (VICL) National Institute of Allergy and Infectious Diseases $3.1 Phase II SBIR grant The grant will partially fund ongoing development of Vical’s immunotherapeutic DNA vaccine against cytomegalovirus disease (3/10) VisiGen Biotechnologies Inc.* National Institutes of Health ND Phase I SBIR grant The grant will support development of a method for labeling DNA, RNA and proteins (9/26) VisiGen Biotechnologies Inc.* National Human Genome Research Institute $4.2 Genome grant Three-year grant will help accelerate development of VisiGen’s sequencing technology (8/6) VistaGen Therapeutics Inc.* High Q Foundation Inc. ND Funding support High Q will support VistaGen’s preclinical studies of AV-101 for treating Huntington’s disease (8/1 1) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 161 2005 Grants And Awards To Biotech Companies (Continued) Company* (Symbol)** Funding Institution Amount (M) Type Details (Date) VistaGen Therapeutics Inc.* National Institute of Drug Abuse $0.197 Phase I SBIR grant The grant will support completion of preclinical efficacy studies of AV-10 1 for treating pain caused by various conditions (7/12) VistaGen Therapeutics Inc.* National Institute of Neurologic Disorders and Stroke $3.7 Development grant The grant will cover the preclinical development of 4-C1-KYN (AV-101) in epilepsy (5/24) Xanthus Life Sciences Inc.* National Cancer Institute $2.3 Grant Xanthus gets up to $2.3M to develop its ParaMetabolic technology to improve the way cancer drugs are dosed (9/29) Xantos Biomedicine AG*, NascaCell IP GmbH and PSF Biotech AG* (all in Germany) German Ministry for Education and Research ND BioChancePLUS program grant The grant will help the firms’ efforts to identify and develop drugs to inhibit tumor angiogenesis, using an aptamer-based approach (4/13) Xantos Biomedicine AG* (Germany) European Union ND 6th Framework Program grant Four-year project to discover and validate targets and pathways involved in tumor-induced blood vessel formation (2/23) XOMA Ltd. (XOMA) National Institute of Allergy and Infectious Diseases $15 Contract award 18-month contract calls for XOMA to develop monoclonal antibody therapeutics against botulinum neurotoxin (3/10) Zen-Bio Inc. National Institutes of Health $0.96 Phase II SBIR grant The two-year grant will support development and characterization of a human omental adipocyte cell system (9/21) Notes: * Indicates a privately held company. Currency conversions reflect values at the time of a deal’s announcement. SBIR = Small Business Innovation Research; STTR = Small Business Technology Transfer. Unless otherwise indicated, symbols listed are on the Nasdaq market. AMEX = American Stock Exchange; ASX = Australian Stock Exchange; CDNX = Canadian Venture Exchange; CSE = Copenhagen Stock Exchange; FSE = Frankfurt Stock Exchange; HEX = Helsinki Stock Exchange; LSE = London Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; PK = Pink Sheets; SSE = Stockholm Stock Exchange; TSE = Toronto Stock Exchange; VSE = Vienna Stock Exchange. 162 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 BIOWORLD ® C O R P O R AT E D E A L S Major Player Novartis Pays Big For Products, Platforms By Randall Osborne West Coast Editor With big pharma firms watching their patents expire and their pipelines dwindle, deal making – both partnerships and outright buyouts – roared forward in 2005, with Novartis AG’s $5.1 billion buyout offer (upped from an earlier, rejected bid of $4.5 billion) to Chiron Corp. stealing the show in November. There is renewed interest in vaccines. Chiron had just won a $62.5 million contract to supply the U.S. government with pre-pandemic vaccine for a stockpile to protect against the H5N1 avian flu virus strain. The vaccine is made at the Liverpool, UK, facility, which hurt Chiron in 2004 when regulators cited sterility issues there related to batches of Fluvirin, and the plant was shut down, causing a shortage of flu shots in the U.S. Chiron acquired the Fluvirin plant in its 2003 buyout of PowderJect Pharmaceuticals plc, and the facility was known to be less than modern. Temporarily closing it cost Chiron, the second-largest vaccine maker in the U.S. and fifth largest in the world, $14 million, plus $5 million in legal fees and $8 million in remediation expenses. It also cost the U.S. half of its flu vaccine, which Chiron had been expected to produce. Novartis still wanted Chiron, which operates other units for blood testing and biopharmaceuticals. Under the terms of the buyout, the pharma giant is paying $45 apiece for about 1 13 million Chiron shares that make up the 58 percent Novartis does not already own. “We’ve always had an interest in vaccines, albeit from a slightly spectator-like position,” said Tony Rosenberg, head of business development and licensing at Novartis. Thomas Ebeling, the company’s CEO, said that “Chiron has not only experience in [the vaccines] field, but is a good discovery organization. Berna Biotech was one of the few companies available other than Chiron, and we took a look.” Novartis backed away from the Berna deal, but Crucell NV in late 2005 bought Berna in an estimated $448 million arrangement. Why did Novartis demur? “It has to make sense of terms of pipeline, earnings outlook and price to BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 165 pay,” Ebeling said. “Sometimes the equation doesn't work out. That was all.” Of Chiron’s Liverpool problems, he said, “It’s behind them. They have good very people and a good track record of outstanding quality management in manufacturing.” Earlier in the year, GlaxoSmithKline plc put $1.4 billion on the table in its buyout of vaccine firm ID Biomedical. GSK had recently won approval for its flu vaccine, Fluarix, and IDB has another, called Fluviral, already marketed in Canada and waiting for clearance in the U.S. In the takeover deal, GSK agreed to pay C$35 per ID Biomedical share held – a premium of 13 percent over the previous day’s closing price, which was the highest closing price ever for IDM, valuing the transaction at C$1.7 billion. When disclosed in September, the GSK buyout of IDM was billed as the largest vaccine deal in history, but that was before Novartis made its eyeopening bid for Chiron. The Swiss pharma firm seemed to want its finger in almost every pie, from companies with products to those with platforms, from large outfits to small. Novartis began 2005 with a deal with Infinity Pharmaceuticals Inc. to jointly design a collection of small molecules using Infinity’s diversity-oriented synthesis program, allowing each to use the resulting compounds in drug discovery efforts. In the spring came a drug-discovery pact with ESBATech AG, which followed a proof-of-concept pilot study using ESBATech’s small-molecule screening technology. Terms call for ESBATech to provide Novartis access to its cellular high-throughput screening technology, and their work will focus on identifying inhibitors for receptor tyrosine kinases that could provide targets for cancer drugs. Financial details were not made public. In April, Novartis tapped Avanir Pharmaceuticals Inc.’s preclinical program to develop small-molecule drugs that target macrophage migration inhibitory factor, in an agreement that could bring $210 million in upfront payments, milestone payments and research funding. The deal typified a move away from the old-style partnerships, in which pharma firms waited until Phase II or later before stepping in. So, to a lesser extent, did the summer’s deal with Arrow Therapeutics Ltd., Arrow’s first – a license to Novartis for A-60444, a small-molecule inhibitor of respiratory syncytial virus, for $10 million down and another $217 million linked to development milestones, plus royalties. The drug was in two Phase II trials, yet to report data. 166 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 The trend rolled on. Summer brought another “largest in history” – this time not vaccines, but the largest Phase I deal ever. Novartis entered a potential $580 million agreement with Anadys Pharmaceuticals Inc., to advance ANA975 and other Toll-like receptor 7 oral prodrugs for chronic hepatitis C and hepatitis B viruses. After a $20 million license payment, Anadys is in line for as much as $550 million in milestones. “We have relatively little in-house capability” in hepatitis, Rosenberg said, adding that Novartis has “looked at it very systematically. Most of our deal making is driven by a strategy where we pick disease areas in which we want to be leaders in the next five to 10 years. We won’t do one deal [in an indication] and one drug.” With partner Idenix Pharmaceuticals Inc., Novartis in January 2006 submitted a new drug application to the FDA for telbivudine, an oral therapy for chronic hepatitis B. Novartis takes special notice of “categories where you need multiple drugs to treat a patient,” Ebeling said. “Our strategy is always to be present in the most relevant mechanism to treat a disease. HCV is the big one, but there are some interesting ones in the infectious disease field. HIV is a little bit more challenging, not as promising.” At almost the same time as the Anadys deal, Novartis put the pen to a pact with Hybridon Inc., hoping to leverage the latter’s immune modulatory oligonucleotide platform to find TLR9 candidates for asthma and allergy. Superlatives trailed in the wake of another deal in the fall, that one focused on RNA interference. Novartis agreed to pay Alnylam Pharmaceuticals Inc. potentially more than $700 million and bought almost 20 percent of the firm in what was described as a “landmark” partnership. The same month, Novartis signed with the platform company Avalon Pharmaceuticals Inc., which focuses on large-scale gene-expression analysis, to collaborate on small-molecule therapeutic compounds targeted against a pathway selected by Novartis, and with NexMed Inc., in a licensing deal worth up to $51 million for worldwide rights to an onychomycosis nail lacquer treatment. “You can track our deals,” Rosenberg said, and determine the main areas of interest for Novartis – cardiovascular, oncology, transplantation and central nervous system disorders, “though we haven’t done many CNS deals in the last couple of years.” Uncommonly, Novartis also has a generics business, making money in BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 167 an area that most other drug developers regard as one to compete with, and dread. “We have a very simplistic view of the world,” Ebeling said. “Our core competence is selling drugs, innovative medicines. Generics are a fact of life. We think they will continue to exist and remain a dynamic, interesting market. Why should we not compete in generics? Maybe other companies have difficulties to envision how the organization can manage this, but we understand the generic mindset much better than other pharma players. We keep them separate, so both are not slowing down each other. I don’t think this is a contradiction; it’s a very good enrichment.” ■ 168 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Value (M)*** Terms/Details I. COMPLETED MERGERS AND ACQUISITIONS Pharmaceutical division of aaiPharma Inc. (PK:AAIIQ) Xanodyne Pharmaceuticals Inc.* 5/10/05 7/12/05 $209.3 Xanodyne paid $209.25M cash to acquire the pharmaceutical assets of aaiPharma in a deal approved by a bankruptcy court; Xanodyne also committed to purchase up to $30M in services from aaiPharma’s services division over three years Absalus Inc.* EvoGenix Pty. Ltd.* (Australia) 4/5/05 4/5/05 $8 The privately held firms merged in a deal valued at $8M in stock; they had been collaborating on antibody therapeutics Oral care business of Access Pharmaceuticals Inc. (AMEX:AKC) Uluru Inc.* 10/12/05 10/12/05 $9.7 The deal’s value could increase to $20.6M; Uluru, set up by Access’s former CEO, acquired Aphthasol, all OraDisc products and all Residerm products; Uluru already had entered an agreement to be acquired by Oxford Ventures Inc. (OTC BB:OXFV) A.C.T. Holdings Inc. (OTC BB: ACTH) Advanced Cell Technology Inc.* 1/3/05 2/1/05 ND The companies completed a reverse merger; prior to the deal Advanced Cell raised $8M privately ActivX Biosciences Inc.* Kyorin Pharmaceutical Co. Ltd. (Japan) 12/1/04 2/2/05 $21 ActivX survives as a wholly owned subsidiary and will serve as Kyorin’s discovery and development center in the U.S.; they have been collaborating since 2002 Aerogen Inc. (OTC BB:AEGN) Nektar Therapeutics (NKTR) 8/15/05 10/20/05 $32 Nektar earlier said it was exercising its option to make it an all-cash deal, at 75 cents per share Afmedica Inc.* Angiotech 9/13/05 Pharmaceuticals Inc. (Canada; ANPI) 10/7/05 ND Afmedica is developing perivascular technology using the drug rapamycin to treat various diseases Agencourt Bioscience Corp.* Beckman Coulter Inc. 4/27/05 6/1/05 $100 Beckman Coulter paid $100M at closing and will make up to $40M in contingent payments through 2007 Altadyne Inc. (OTC BB:ATYD) Stem Cell Therapy International Corp.* 9/16/05 9/16/05 ND The merged company will keep the Stem Cell Therapy International name; the ticker symbol will be changed BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 169 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Alteris Therapeutics Inc.* Date Completed Value (M)*** Celldex 10/12/05 Therapeutics Inc. (majority owned by Medarex Inc.; MEDX) 10/12/05 ND Celldex issued 1.2M shares, paid $1.5M in cash and could make milestone and other payments for Alteris, which has the Phase II cancer vaccine ALT-1 10 Amedis Pharmaceuticals Ltd.* (UK) Paradigm Therapeutics Ltd.* (UK) 1/7/05 1/7/05 ND Both are early stage companies based in Cambridge, UK; terms were not disclosed Anawah Inc.* Arcadia Biosciences Inc.* 5/16/05 5/16/05 ND Arcadia, an ag-biotech company, acquired Anawah, which focuses on developing value-added whole foods Angiosyn Inc.* Pfizer Inc. 1/20/05 4/6/05 $527 Angiosyn stockholders received up-front and other payments of up to $527M; they also would get royalties on future sales; full payment is contingent on successful development of a drug for an ophthalmic indication and a second therapeutic area APS Pharma GmbH* (Germany) ProStrakan Group plc* (UK; LSE:PSK) 5/3/05 5/3/05 €2.7 ($3.4) ProStrakan gained a sales and marketing infrastructure in Germany through the allcash acquisition Aptamera Inc.* Antisoma plc (UK; LSE:ASM) 1/10/05 2/4/05 £1 1.5 ($21.6) Antisoma issued up to 66.5M shares, or 20% of the enlarged company, to acquire Aptamera, which is developing AGRO100, an anticancer aptamer Arakis Ltd.* (UK) Sosei Co. Ltd. (Japan) 7/19/05 8/30/05 £106.5 ($186) Sosei paid £1 1.7M cash and issued 35,630 shares in the deal, or 33.6% of the enlarged company Arexis AB* (Sweden) Biovitrum AB* (Sweden) 8/22/05 8/22/05 ND Biovitrum will make cash and equity payments up front and will pay more in cash and stock if milestones are reached Most assets of Argonaut Technologies Inc. (AGNT) Biotage AB (Sweden; SSE: BIOT) 2/22/05 6/6/05 $21.2 Biotage paid $21.2M for the chemistry consumables business and certain assets of Argonaut’s process chemistry business, which constitute all Argonaut assets except its cash; Argonaut no longer has an operating business 10/20/05 10/20/05 ND The merged company will change its name and stock symbol to reflect the Cardium Therapeutics Inc. ownership Aries Ventures Cardium Inc. (OTC BB:ARVT) Therapeutics Inc.* 170 Date Announced Terms/Details BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Value (M)*** Artesian Therapeutics Inc.* Cardiome Pharma Corp. (Canada; CRME) 8/29/05 10/24/05 N/A Artesian shareholders can earn up to $32M in payments for development milestones related to each of two drug candidates Arthron Pty. Ltd. (Australia; subsidiary of Prima Biomed Ltd.) Trillium Therapeutics Inc.* (Canada) 10/6/05 10/6/05 ND Prima got $0.5M up front in cash and 5.6% of TTI’s stock; Prima also is entitled to receive additional TTI shares if certain milestones are met Artus GmbH* (Germany) Qiagen NV (the Netherlands; QGEN) 5/31/05 5/31/05 $27.6 Qiagen paid $27.6M in cash and would pay $1 1.6M more if certain milestones are met; Artus focuses on PCR-based molecular diagnostic tests Asterand Inc.* Pharmagene plc (UK; LSE:PGN) 9/19/05 12/22/05 £13 ($23.5) Asterand shareholders got about 54.2M shares in the deal, or 50% of the merged company, and could get additional payments; the name was changed to Asterand plc Astral Inc. Astral (subsidiary of Therapeutics Alliance Inc.* Pharmaceutical Corp.; OTC BB:ALLP) 9/7/05 9/7/05 ND Astral Therapeutics, set up for this deal, will be renamed MultiCell Immunotherapeutics Inc. and be owned 33% by Alliance and 67% by MultiCell Technologies Inc. (OTC BB:MCET) Atugen AG* (Germany) SR Pharma plc (UK; AIM:SPA) 6/21/05 7/1 1/05 £6.2 ($10.8) SR Pharma issued 19.7M shares, or 49% of of the enlarged company, in the acquisition Austin Research Institute companies (Australia) Prima Biomed Ltd. (Australia; ASX:PRR) 8/9/05 8/25/05 ND Prima acquired about 100% of four subsidiaries from ARI: Cancer Vac Pty. Ltd., Panvax Ltd., OncoMab Pty. Ltd. and Athron Ltd.; ARI got a stake of about 10% in Prima Biomed Auvation Ltd.* (UK) EiRx Therapeutics plc (Ireland; AIM:ERX) 1/5/05 1/5/05 £1.5 ($2.6) EiRx acquired 56.1% percent of Auvation from Auvation’s founder and chairman for £1.5M in stock, and is offering to buy the rest of the company on the same terms Aventis Pharmaceuticals Puerto Rico Inyx Inc. (OTC BB:IYXI) 10/7/04 3/31/05 $19.7 The production and development center in Puerto Rico was a unit of the Sanofi-Aventis Group Axxima Pharmaceuticals AG* (Germany) GPC Biotech AG (Germany; GPCB) 3/2/05 3/2/05 €13.7 ($18) GPC issued 1.3M shares for Axxima, a kinase discovery firm that filed for insolvency in December; Axxima investors invested €8.7M in Axxima as part of the deal BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Terms/Details 171 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Value (M)*** Binax Inc.* Inverness Medical Innovations Inc. (AMEX:IMA) 2/8/05 3/31/05@ $44.7 Inverness issued 1.4M shares of stock and paid $9M in cash for the diagnostics company; Binax shareholders could earn up to $1 1M more if certain objectives are reached within five years Bio Asia* (China) Invitrogen Corp. (IVGN) 12/8/04 3/24/05 $8 Invitrogen paid up to $8M in cash for Bio Asia, which provides products to the Chinese research community BioCell Pty. Ltd.* (Australia) Cygenics Ltd. 1 1/7/05 (Australia; ASX:CYN) 1 1/7/05 ND Cygenics acquired a 51% controlling interest in BioCell, a cord blood stem cell banking business BioCheck Inc.* OXIS International Inc. (OTC BB:OXIS) 9/21/05 12/8/05 $6 OXIS completed the first closing of the deal, paying $3.06M in cash for $51% of BioCheck, a producer of enzyme immunoassay kits BioFocus plc (UK; AIM:BIO) Galapagos NV (Belgium; Euronext:GLPG) 9/21/05 10/17/05 £20.2 ($35.6) Galapagos paid 124 pence in stock for each BioFocus share, a premium of 121% to the Sept. 20 closing price; BioFocus owns about 30% of the combined company Biofrontera Discovery GmbH* (Germany) Discovery Partners International Inc. (DPII) 3/1/05 4/22/05 ND Discovery Partners paid an undisclosed amount in cash for Biofrontera Discovery, formerly the natural products discovery division of Biofrontera AG Biogenesis Ltd.* (UK) and Biogenesis Inc.* MorphoSys AG 1/20/05 (Germany; FSE:MOR) 1/20/05 £5.25 ($9.8) The Biogenesis companies, which focus on antibody development and manufacturing, became wholly owned subsidiaries of MorphoSys BioPixels unit of BioCrystal Ltd. Invitrogen Corp. (IVGN) 10/6/05 10/6/05 ND Terms of the acquisition were not disclosed Bioren Inc.* Pfizer Inc. 8/15/05 8/15/05 ND Pfizer paid an undisclosed amount for Bioren, which has technology for optimizing antibodies BioSource International Inc. (BIOI) Invitrogen Corp. (IVGN) 7/26/05 10/6/05 $130 Invitrogen strengthened its position in proteomics through the all-cash acquisition 172 Terms/Details BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Antibody and peptide business BioSource International Inc. (BIOI) Quality Controlled Biochemicals* 1/3/05 1/3/05 ND Dennis DiSorbo, the former general manager of the business, bought the antibody of and peptide business, which was renamed Quality Controlled Biochemicals Biosynexus Inc.* QVT Fund LP 6/14/05 6/14/05 ND Biosynexus became a wholly owned subsidiary of the fund; terms of the deal were not disclosed Bioxalis Medica Inc.* (Canada) Procyon Biopharma Inc. (Canada; TSE:PBP) 6/30/05 6/30/05 C$3.42 ($2.8) Procyon issued 9M shares to acquire Bioxalis, which focuses on targeted liposomes for treating cancer; Bioxalis shareholders also got 1M warrants exercisable at market price, if a development milestone is met Bliss Clearant Essentials Corp.* Corp. (OTC BB:BLSE) 4/1/05 4/4/05 ND Clearant acquired Bliss in a reverse merger; the symbol on the OTC BB was changed to “CLRI” Bone Care International Inc. (BCII) Genzyme Corp. (GENZ) 5/4/05 6/30/05 $600 Genzyme paid $33 in cash for each Bone Care share; Genzyme intends to integrate Bone Care into its renal operations, while maintaining Bone Care’s facility in Wisconsin Caltag Laboratories* Invitrogen Corp. (IVGN) 5/16/05 5/19/05 $20 Invitrogen acquired the immunological assay manufacturer in an all-cash deal Certain assets Maxim of Calypte Biomedical Biomedical Corp. Inc.* (AMEX:HIV) 4/21/05 1 1/21/05 ND As part of a restructuring, Calypte sold its urine EIA, serum Western Blot and urine Western Blot HIV in vitro diagnostics business Cambridge Biotechnology Ltd.* (UK) Biovitrum AB* (Sweden) 3/21/05 4/25/05 ND CBL, which is developing drugs to treat obesity, pain and inflammation, will operate as an autonomous R&D unit in the UK uHTS business of Carl Zeiss Group (Germany) Evotec OAI AG (Germany; FSE: EVT) 5/9/05 5/9/05 ND Evotec Technologies GmbH acquired the ultra-high-throughput business of Zeiss and assumed service responsibility for installed instruments CeeTox Inc.* North American 5/24/05 Science Association Inc.* 5/24/05 ND NAMSA acquired 51% of CeeTox and would purchase the remainder as certain milestones are reached BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Value (M)*** Terms/Details 173 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Value (M)*** Cellective Therapeutics Inc.* MedImmune Inc. (MEDI) 9/14/05 10/17/05 ND MedImmune made an up-front payment and could add milestone payments that together total $160M for Cellective, which is developing monoclonal antibodies that target B-cell antigens Celltech Manufacturing Services Ltd. (UK; unit of UCB) Inyx Inc. (OTC BB:IYXI) 8/26/05 8/31/05 €27.5 ($34) The manufacturing facility’s name was changed to Ashton Pharmaceuticals Ltd.; it will operate as Inyx Europe Ltd. Celmed BioSciences Inc.* (Canada) Theratechnologies Inc. (Canada; TSE:TH) 6/20/05 6/20/05 C$2.8 ($2.3) A group of minority Celmed shareholders purchased Theratechnologies’ 37% stake in the company; the total could increase to C$8.4M if certain milestones are reached Cita NeuroPharmaceuticals Inc.* (Canada) Vernalis plc (UK; VNLS) 1 1/18/05 12/14/05 £17 ($29.8) Vernalis issued 26.9M shares in the deal, 24.3M of which concurrently were sold in a private placement that brought Cita shareholders £15.5M in gross proceeds Computational Biology Corp.* Agilent Technologies Inc. (NYSE:A) 1/5/05 1/5/05 ND Agilent acquired CBC, which developed a microarray-based technique for analysis of gene regulation in disease Control Delivery Systems Inc.* pSivida Ltd. (Australia; PSDV) 10/3/05 1 1/15/05 $88 CDS shareholders received 1 6M pSivida American depositary shares in the deal, representing 40% of the merged company Corgentech Inc. (CGTK) AlgoRx Pharmaceuticals Inc.* 9/26/05 12/16/05 ND AlgoRx shareholders received Corgentech stock representing 62% of the merged company Corixa Corp. (CRXA) GlaxoSmithKline plc (UK) 5/2/05 7/12/05 $300 GSK paid $4.40 in cash for each Corixa share, a 48% premium to the April 28 closing price; they had been collaborating on development of vaccines CyVera Corp.* Illumina Inc. (ILMN) 2/22/05 4/1 1/05 $16.8M Illumina issued 1.6M shares and paid $2.5M in cash for CyVera, which has a digital microbead platform Delex Therapeutics Inc.* (Canada) YM BioSciences Inc. (Canada; TSE:YM) 4/13/05 5/3/05 C$10.1 ($8) YM issued about 1.59M shares in the deal initially and will issue about 1.82M more shares over two years; Delex could earn another 2.78M shares related to milestones on its Phase II product AeroLEF for pain in cancer patients and $4.75M in cash or shares upon a product approval 174 Terms/Details BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Diagnostic Systems Laboratories Corp.* Date Announced Date Completed Value (M)*** Beckman Coulter 10/7/05 Inc. 10/18/05 ND DSLC provides specialty immunoassays, including technology for reproductive endocrinology and cardiovascular risk assessment Discovery Innovations Inc.* Entelos Inc.* 5/26/05 5/26/05 ND Entelos acquired Discovery Innovations, which provides data integration products and services for the life sciences Discovery Systems unit of Discovery Partners International Inc. (DPII) Nexus Biosystems Inc.* 10/7/05 10/14/05 $1.5 Nexus acquired the IRORI chemical synthesis systems, Crystal Farm automated protein crystallization and Universal Store compound storage systems businesses; Nexus was set up by Discovery’s former chief technology officer Dragon Pharmaceutical Inc. (Canada; TSE:DDD) Oriental Wave Holding Ltd.* (China) 3/24/04 1/14/05 ND Companies merged in a deal giving Dragon about 31.65% of the combined company; Oriental Wave, incorporated in the British Virgin Islands, is the sole shareholder of a China-based pharmaceutical company Dynal Biotech* (Norway) Invitrogen Corp. (IVGN) 2/8/05 4/1/05 NOK2.5B ($391) Invitrogen purchased the company, which is focused on magnetic bead technologies, from majority-owner Nordic Capital and a co-investor EasyWeb Inc. (OTC BB:ESWB) ZioPharm Inc.* 8/3/05 9/15/05 ND The combined company is named ZioPharm Oncology Inc.; the ticker symbol was changed to “OTC BB:ZIOP” Echelon Biosciences Inc.* AEterna Zentaris Inc. (Canada; AEZS) 1/6/05 1/6/05 $2.7 AEterna issued 443,905 shares valued at $2.7M in the deal; Echelon shareholders could earn another $2.9M in stock if certain milestones are reached Emergent Genetics Inc.* Monsanto Co. 2/17/05 4/5/05 $300 Monsanto paid $300M in cash and commercial paper for the cotton seed company Esoterix Inc.* Laboratory Corp. 3/30/05 of America Holdings 5/1 1/05 $150 LabCorp paid $150M in cash for Esoterix, a provider of specialty reference testing ESP Pharma Holding Co. Inc.* Protein Design Labs Inc. (PDLI) 3/24/05 $486 PDL paid $325M in cash and issued 9.85M shares to acquire ESP, which was founded around the acquisition of several products from Wyeth 1/25/05 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Terms/Details 175 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Evotec Neurosciences (UK) Evotec OAI AG (Germany; FSE:EVT) 3/6/05 3/6/05 Eyetech Pharmaceuticals Inc. (EYET) OSI Pharmaceuticals Inc. (OSIP) 8/21/05 1 1/14/05 GemVax A/S* (Norway) Pharmexa A/S (Denmark; CSE: PHARMX) 4/12/05 Genaissance Pharmaceuticals Inc. (GNSC) Clinical Data Inc. (CLDA) 6/21/05 GenBase Inc.* Value (M)*** Terms/Details €49 ($65.5) Evotec issued 14.3M shares to acquire the 78% of ENS it did not already own; ENS was formed by Evotec in 1999 and focuses on central nervous system diseases $935 OSI paid stock and cash worth $20 per Eyetech share, a 43% premium to the Aug. 19 price; 75% of the price was paid in cash 6/9/05 DKK32 ($4.9) Pharmexa issued 1.4M shares worth DKK32M in the deal, and would pay another DKK33M if the cancer vaccine GV100 1 enters Phase III trials by September 2006 10/7/05 $56 Genaissance shareholders received about 2.3M Clinical Data shares in the deal, as well as preferred stock and options and warrants Integrated DNA 12/15/05 Technologies Inc.* 12/15/05 ND GenBase is a supplier of custom oligonucleotides Genencor International Inc. (GCOR) Danisco A/S (Denmark; CSE: DCO) 1/27/05 4/20/05 $592 Danisco paid $1 9.25 per share for the shares it did not not already hold; it already held 42% of Genencor, as did Eastman Chemical Co., which agreed to the sale GeneXP BioSciences Inc.* MetriGenix Inc.* (Canada) 12/15/04 6/7/05 ND GeneXP is developing a portfolio of gene expression biomarker tests; terms of the deal were not disclosed Global Genomics AB* (Sweden) Genizon BioSciences Inc.* (Canada) 5/1 1/05 5/1 1/05 ND Genizon acquired the majority of the assets and staff of Global Genomics, which has sequencing and data-analysis technologies GlycArt Biotechnology AG* (Switzerland) F. HoffmannLa Roche Ltd. (Switzerland) 7/19/05 7/26/05 CHF235 ($183) Roche paid cash to acquire GlycArt; GlycArt has GlycoMAb glycosylation technology, which increases antibody-dependent cellular cytotoxicity Greenwich Therapeutics* VioQuest 5/4/05 Pharmaceuticals Inc. (OTC BB:VQPH) 10/19/05 $7.3 Greenwich got 17.1M shares of VioQuest stock and five-year warrants to purchase another 4M shares at $1.41; release of half the shares and warrants are tied to milestones related to Phase I and II trials of two cancer compounds; the value is based on half the shares at the Oct. 18 closing price 176 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed G2M Cancer Drugs AG* (Germany) TopoTarget A/S* (Denmark) 3/1/05 3/1/05 Guilford Pharmaceuticals Inc. (GLFD) MGI Pharma Inc. (MOGN) 7/21/05 10/3/05 Hematech LLC* Kirin Brewery Co. Ltd. (Japan) 7/25/05 Hormos Medical Corp.* (Finland) QuatRx Pharmaceuticals Co.* H3 Pharma* (Canada) Value (M)*** Terms/Details ND TopoTarget acquired G2M, which is developing HDAC inhibitors for cancer indications $177.5 MGI issued 5.3M shares and paid $53.9M in cash, equaling $3.75 per Guilford share; the price was a 55.6% premium to Guilford’s July 20 close 7/25/05 $45 Kirin paid cash for Hematch, which produces bovine-derived polyclonal antibodies; the companies began working together in 1999 on the development of human antibody-producing cows 5/16/05 5/16/05 ND Hormos became a wholly owned subsidiary of QuatRx; offices will be maintained in Finland Debiopharm SA* (Switzerland) 3/1/05 3/1/05 ND Debiopharm purchased all the outstanding shares of H3 Pharma from Societe Generale de Financement du Quebec; Debiopharm and SGF created H3 Pharma in 2001 HVL Inc./ Douglas Laboratories Atrium Biotechnologies Inc. (Canada; TSE: ATB) 12/8/05 12/8/05 C$107 ($92) Atrium, 48.5% owned by AEterna Zentaris Inc., paid C$97M in cash and C$10M in stock for HVL, which has been marketing health and nutritional products for more than 50 years Icoria Inc. (OTC BB:ICOR) Clinical Data Inc. (CLDA) 9/20/05 12/20/05 $1 1 Icoria shareholders received stock representing about 7.6% of the merged company ID Biomedical Corp. (Canada; IDBE) GlaxoSmithKline plc (UK) 9/7/05 12/8/05 C$1.7B ($1.4B) GSK paid C$35 per share, or C$1.7B, a premium of 13% to the price before the deal’s announcement; GSK also assumed US$77 million in ID debt Idun Pharmaceuticals Inc.* Pfizer Inc. 2/24/05 4/12/05 ND Idun focuses on the discovery and development of therapies to control apoptosis; terms of the deal were not disclosed Igeneon AG* (Austria) Aphton Corp. (APHT) 12/15/04 3/24/05 $27.1 Igeneon stockholders received 2 1.5M Aphton shares in the deal; Igeneon became a wholly owned Aphton subsidiary IngenKO Pty. Ltd.* (Australia) GenOway SA* (France) 10/7/05 10/7/05 ND GenOway took over the commercial activities for IngenKO following the Australian company’s closure BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 177 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Value (M)*** Iliad Chemicals Pty. Ltd. (Australia) Bionomics Ltd. (Australia; ASX:BNO) 5/25/05 6/26/05 A$9 ($6.8) Bionomics issued about 40.9M shares in the deal, and would issue 1 3.6M more shares worth A$3M if certain milestones are met ImmunoDesigned Molecules SA* (France) Epimmune Inc. (EPMN) 3/16/05 8/16/05 $105 IDM shareholders hold about 78% of the merged company, which was renamed IDM Pharma Inc.; the new Nasdaq symbol is “IDMI” ImVision GmbH (subsidiary of BioVision AG; Germany) Nextech Venture LP (Switzerland) 5/3/05 5/3/05 ND The Swiss investment firm purchased the BioVision spin-off, which is developing immunotherapeutics based on its modular antigen transport technology Inhibetex Therapeutics Inc.* Organic Soils.com 3/29/05 Inc. (OTC BB: OSLC) 5/26/05 ND Inhibetex owns about 83% of the company following the reverse merger; the company changed its name to Inhibition Therapeutics Inc., and the stock symbol changed to “IHBT” InKine Pharmaceutical Co. Inc. (INKP) Salix Pharmaceuticals Inc. (SLXP) 6/23/05 10/3/05 $190 InKine shareholders received 9M Salix shares in the deal; InKine will continue as a wholly owned Salix subsidiary Inovio A/S* (Norway) Genetronics Biomedical Corp. (AMEX:GEB) 1/26/05 1/26/05 $10 Genetronics paid $3M in cash and $7M in shares of Series D convertible stock in the deal for the gene-delivery company; the value would increase if milestones are met Ionix Pharmaceuticals Ltd.* (UK) Vernalis plc (UK; VNLS) 7/6/05 7/26/05 £12.5 ($22) Vernalis issued about 17.85M shares in the deal, or 8% of the company; Ionix shareholders will get another 1.84M shares in July 2006 Ischemia Technologies Inc.* Inverness Medical Innovations Inc. (AMEX:IMA) 2/16/05 3/16/05 $20.7 Inverness issued about 970,000 shares to acquire Ischemia, which markets an in vitro diagnostic test for cardiac ischemia Ivory Capital Corp. (OTC BB: IVRC) Chelsea Therapeutics Inc.* 1/21/05 2/16/05 ND Chelsea shareholders own about 96.75% of the combined company following the reverse merger; the trading symbol has changed to CHTP 2/22/05 2/22/05 ND Julich provides products and services for the biocatalytic production of chiral pharmaceutical intermediates; terms were not disclosed Julich Fine Codexis Inc.* Chemicals GmbH* (Germany) 178 Terms/Details BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed LemnaGene SA* (France) Biolex Therapeutics Inc.* 7/28/05 7/28/05 ND LemnaGene is using the aquatic plant Lemna to produce recombinant proteins; Biolex also has a Lemna-based manufacturing program Lifespan ePTFE business of Edwards Lifesciences Corp. Angiotech 1 1/3/05 Pharmaceuticals Inc. (Canada; ANPI) 12/1/05 $14 Angiotech paid $1 4M in cash for the vascular graft business; Edwards retains certain distribution rights Lorantis Ltd.* (UK) Celldex 10/12/05 Therapeutics Inc. (majority owned by Medarex Inc.; MEDX) 10/12/05 ND Celldex issued 6.8M shares of Class A common stock for Lorantis, which brings a preclinical program in immunity and $30M in cash LumiCyte Inc.* Qiagen NV (the Netherlands; QGEN) 8/1/05 8/8/05 $3 Qiagen is paying $3M up front in the acquisition; milestone payments of up to $13M relating to financial targets could be paid in 18 to 60 months Lynx Therapeutics Inc. (LYNX) Solexa Ltd.* (UK) 8/13/04 3/7/05 $142 Solexa was issued 14.75M shares in the deal and owns 80% of the combined company, named Solexa Inc. and trading under the “SLXA” ticker symbol Medac GmbH* (Germany) Schering AG (Germany) 6/9/05 6/9/05 ND Medac shareholders purchased the 25% stake held by Schering for a two-digit million-euro price; Schering also acquired from Medac the remaining 50% of their joint venture, Medac Schering Onkologie GmbH Metagen Pharmaceuticals Inc.* Esprit Pharma Inc.* 9/16/05 9/16/05 ND Esprit acquired Metagen and its operating subsidiaries, Star Pharmaceuticals and Stellar Pharmacal; terms were not disclosed Microscience Ltd.* (UK) Emergent BioSolutions Inc.* 6/27/05 6/27/05 $73 Microscience, which pulled its plans for an IPO in July, was acquired for stock valued at $73M; its name changed to Emergent Europe Molecular Engine Laboratories* (France) Cerep SA (France; Nouveau Marche:CERF) 5/25/04 1/7/05 €4.7 ($6.1) Cerep issued 400,000 shares in the deal, or 3.35% of the merged company; Cerep also would pay royalties of 5% or 8% to MEL shareholders on the first diagnostic and therapeutic products approved or licensed Molecular Imaging Corp.* Agilent Technologies Inc. (A) 1 1/29/05 1 1/29/05 ND Molecular Imaging developed atomic force microscopes, which are used by nanotechnology researchers BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Value (M)*** Terms/Details 179 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Molecular SkinCare Ltd.* (UK) York Pharma plc (UK; LSE:YRK) 2/1/05 2/1/05 MRC Geneservice* (UK) Medical Research Council (UK) 6/6/05 6/6/05 ND Management of MRC Geneservice bought the unit, and renamed it Geneservice Ltd.; terms were not disclosed Multichem Inc.* (Canada) AEterna Zentaris Inc. (Canada; AEZS) 1/25/05 1/25/05 C$23.8 ($19.2) Atrium Biotechnologies Inc., a majorityowned AEterna subsidiary, paid C$22.2M of the total in cash; Multichem sells active ingredients and specialty chemicals Murinus GmbH* (Germany) GenOway SA* (France) 1/12/05 1/12/05 ND Murinus provides genetically modified animal models and offers transgenic services; terms of the deal were not disclosed Microarray unit of MWG Biotech AG (Germany; FSE:NWUG) Ocimum Biosolutions (India) 2/25/05 4/25/05 ND Ocimum will continue MWG operations in Germany, and plans to start wet lab services in India as part of the expansion Neighborhood Lpath Connections Therapeutics Inc. (OTC BB:NBHC) Inc.* 7/15/05 12/8/05 ND Lpath acquired Neighborhood Connections in a reverse merger; the name was changed to Lpath Inc. and the ticker symbol to OTC BB:LPTN NeoGenesis Pharmaceuticals Inc.* Schering-Plough Corp. 1/20/05 2/18/05 ND Terms of the deal were not disclosed; they have been collaborating since 1999; NeoGenesis has screening and chemistry technologies for small-molecule drug discovery Neurofit* (France) Bionomics Ltd. (Australia; ASX:BNO) 12/16/04 3/2/05 €1.25 ($1.65) Bionomics paid €1M in cash and €0.25M in stock to acquire Neurofit, which conducts contract research and preclinical testing Nexia Biotechnologies Inc. (Canada; TSE:NXB) PharmAthene Inc.* 1/6/05 3/10/05 $18 PharmAthene paid $1 1.2M in cash and issued 7.5 million Series C convertible preferred shares at $0.91 per share, as well as warrants to acquire 1.3M shares Nextal Biotechnology Inc.* (Canada) Qiagen NV (the Netherlands; QGEN) 6/30/05 7/1/05 $9.7 Qiagen is paying $9.7M in cash and would pay another $4.5M if certain milestones are met; Nextal provides sample preparation tools NovaScreen Biosciences Corp.* Caliper Life Sciences Inc. (CALP) 9/8/05 10/4/05 $22 Caliper paid $22M and could pay up to $8M more if revenue milestones over 30 months are reached; payment was 80% in stock and 20% in cash 180 Value (M)*** £5.5 ($10.3) Terms/Details York issued about 5M shares in the deal BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed NovAseptic AB* (Sweden) Millipore Corp. 7/7/05 8/9/05 Nurel Therapeutics Inc.* Diamyd Medical AB (Sweden; SSE:DIAMB) 1 1/22/05 12/16/05 O.E.M. Concepts Inc.* Meridian Bioscience Inc. (VIVO) 1 1/10/04 Optive Research Inc.* Tripos Inc. (TRPS) Orphan Medical Inc. (ORPH) Osmotics Pharma Inc.* Value (M)*** Terms/Details SEK720 ($91) Millipore is paying $9 1M in cash for NovAseptic, which provides solutions for aseptic processing applications in drug manufacturing operations $1.5 Diamyd issued stock valued at $1.5M in the deal, as well as stock to pay off Nurel loans; the shares represent about 4% of Diamyd 2/1/05 $6 O.E.M. received $6M in cash in the deal and could earn another $2.3M over four years 12/22/04 1/5/05 $7.9 Tripos issued 599,52 1 shares that were valued at $3.17M and paid $4.75M in cash for Optive, which develops software for computer-assisted molecular discovery Jazz Pharmaceuticals Inc.* 4/19/05 6/24/05 $145 Privately held Jazz paid $10.75 per share in cash for Orphan’s outstanding shares, a premium of about 26% to the close the day before the deal was disclosed OnSource Corp. (OTC BB:OSCE) 4/12/05 5/1 1/05 ND OnSource issued about 1 1.4M shares, giving OPI 92% of the combined company; OnSource also issued 1M shares of 6% convertible stock worth $4M, 1.1M warrants and 2.7M stock options; the firm’s name changed to Ceragenix Pharmaceuticals Inc. and the symbol changed to “CGXP” Panacos V.I. Technologies 6/3/04 Pharmaceuticals* Inc. (VITX) 3/1 1/05 $166 Vitex issued 227.5M shares in the deal, leaving Panacos with about 80% ownership of the combined company ParAllele BioScience Inc.* Affymetrix Inc. (AFFX) 5/31/05 10/24/05 $132.5 Affymetrix issued 2.29M shares worth $120.8M and paid $1 1.7M in cash to acquire ParAllele, with which it had been partnered for two years Peninsula Pharmaceuticals Inc.* Ortho-McNeil 4/19/05 Pharmaceuticals Inc. (unit of Johnson & Johnson) 6/30/05 $245 The all-cash acquisition did not include Peninsula’s PPI-0903, a broad-spectrum cephalosporin, which will be spun out into a new company, Cerexa Inc. Certain assets of Poalis A/S* (Denmark) Evolva SA* (Switzerland) 9/2/05 ND Evolva acquired the pharmaceutical assets of Poalis; Poalis’ assets in food and flavor chemicals and agriculture were not included in the deal 9/2/05 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 181 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed ProBio International Holdings Pte. Ltd.* (Australia) Pharming Group NV (the Netherlands; Euronext:PHARM) 12/28/04 1/24/05 ND Pharming issued shares representing 1.5% of the company in acquiring the 55% of ProBio it did not already own ProCorde Trigen Holdings GmbH* (Germany) plc* (UK) 4/1 1/05 4/1 1/05 ND The cardiovascular-focused companies merged to form Trigen Holdins AG, which will maintain sites in the UK and Germany ProCyte Corp. (OTC BB:PRCY) PhotoMedex Inc. (PHMD) 12/1/04 3/18/05 $28.2 PhotoMedex issued about 10.5M shares in the deal, giving ProCyte about 21% of the combined company Proteome Inc. (subsidiary of Incyte Corp.; INCY) Biobase GmbH* (Germany) 1/18/05 1/18/05 ND Acquiring Proteome strengthened Biobase’s position in biological databases; terms of the deal were not disclosed Prosidion Ltd.* (UK) OSI Pharmaceuticals Inc. (OSIP) 4/18/05 4/18/05 $4.3 OSI issued 84,940 shares to acquire all the minority-interest shares in its UK subsidiary (about 2.7% of Prosidion) Proxima Therapeutics Inc.* Cytyc Corp. (CYTC) 2/9/05 3/7/05 $160 Cytyc paid $1 60M in cash to acquire Proxima, which could earn up to $65M more based on sales of breast cancerrelated products PsycheNomics Inc.* Novasite Pharmaceuticals Inc.* 6/15/05 6/15/05 ND Novasite acquired PsycheNomics, which focuses on drug discovery for diseases of the central nervous system Pyramid Biological Corp.* Life Therapeutics (ASX:LFE) 7/6/05 9/22/05 $13 Life Therapeutics paid $13M, and assumed $7M in debt; another $5M could be paid if milestones are reached Quadrant Technologies Ltd.* (UK) ML Laboratories plc (UK; LSE:MLB) 6/16/05 7/14/05 £46.7 ($85) Combined company name is Innovata plc; ML paid £1 9.5M cash and the rest in shares as part of the 50-50 merger; ML also paid £1.85M cash and shares to acquire the 18.75% interest in Innovata that Biomed did not already own Quantum Dot Corp.* Invitrogen Corp. (IVGN) 10/6/05 10/6/05 ND Terms of the acquisition were not disclosed Research Diagnostics Inc.* Trinity Biotech Inc. (Ireland; TRIB) 3/21/05 3/21/05 $4.2 Trinity paid $4.2M in cash for RDI, a provider of immunodiagnostic products 182 Value (M)*** Terms/Details BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Rexahn Corp.* Corporate 5/16/05 Roadshow.com Inc. (OTC BB:CPRD) 5/16/05 ND Rexahn owns 92% of the combined company following the reverse merger; the new name is Rexahn Pharmaceuticals Inc., which trades as “RXHN” on the OTC Bulletin Board RNAture Inc. (subsidiary of Hitachi Chemical Research Center Inc.) Qiagen NV (the Netherlands; QGEN) 5/2/05 5/2/05 ND Qiagen bought the commercial operations of RNAture, which include nucleic acid isolation products SagaX Medical Technologies Inc.* MIV Therapeutics Inc. (Canada; OTC BB:MIVT) 3/18/05 3/18/05 ND MIV acquired Sagax, a company incorporated in the U.S. with operations in Israel that is developing devices for cardiovascular applications Salmedix Inc.* Cephalon Inc. (CEPH) 5/12/05 6/14/05 $160 Cephalon paid $160M in cash, and could pay up to $40M more in regulatory milestone payments; Salmedix is developing compounds for hematologic malignancies SansRosa Pharmaceutical Development Inc.* CollaGenex Pharmaceuticals Inc. (CGPI) 12/15/05 12/15/05 $0.75 Collagenex purchased 51% of SansRosa for $0.75M and could pay up to $6M for the rest of the company if milestones are reached with SansRosa’s rosacea program Savetherapeutics AG* (Germany) Medical Discoveries Inc. (OTC BB:MLSC) 3/16/05 3/16/05 €2.35 ($3.14) MDI paid cash to acquire Savetherapeutics, which is developing a topical steroidal form of aromatase inhibitor for breast cancer Scantox Biologisk Laboratorium A/S* (Denmark) LAB International Inc. (Canada; TSE:LAB) 2/10/05 2/10/05 C$6.1 ($5) About 90% of the price was paid on closing, with the remainder payable by March 31, 2006, subject to post-closing adjustments; Scantox is a contract research organization Scientific Software Inc.* Agilent Technologies Inc. (NYSE:A) 5/25/05 7/1 1/05 ND Agilent acquired SSI, a provider of scientific information management solutions Specialty Media division of Sentigen Holding Corp. (SGHL) Chemicon International Inc. (subsidiary of Serologicals Corp.; SERO) 2/22/05 2/22/05 $6.5 The division was part of Cell & Molecular Technologies, which is owned by Sentigen; the division has cell and stem cell research technologies Separtis Holding AG* (Switzerland) Biotage AB (Sweden; SSE:BIOT) 10/6/05 10/6/05 €1.4 ($1.7) Separtis is the Swiss, German and Austrian distributor for many Biotage products BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Value (M)*** Terms/Details 183 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Sertanty Inc.* Eidogen Inc.* 3/9/05 3/9/05 ND The private companies merged to form Eidogen-Sertanty Inc., a provider of chemoinformatics and structural informatics products and services Shanghai Genomics Inc.* (China) GNI Ltd.* (Japan) 6/20/05 6/20/05 ND The companies had been collaborating for more than a year; the combined company has more than 80 employees in Japan, China and the UK Sirenade Pharmaceuticals AG* (Germany) KeyNeurotek AG* (Germany) 12/13/05 12/13/05 ND Both private German firms are focused on central nervous system disorders; Sirenade was formed in 2004 through the merger of Nadag AG and SiREEN AG Stem Cell Ventures Inc. (PK:SCVR; formerly OncBio Inc.) Stem Cell Ventures Ltd.* (UK) 12/6/05 12/6/05 ND Former Stem Cell Ventures Ltd. shareholders own 94.8% of the combined company following the reverse merger Stressgen Bioreagents Corp.* Assasy Designs Inc. 7/12/05 7/12/05 ND Stressgen Bioreagents was spun out of Stressgen Biotechnologies Corp. in May; Ampersand Ventures funded both deals Bioreagents business of Stressgen Biotechnologies Corp. (Canada; TSE:SSB) Stressgen Bioreagents Corp.* 4/13/05 5/2/05 C$8 ($6.4) Twenty-six of Stressgen’s 103 employees joined the newly formed bioreagents company, which was funded by Ampersand Ventures Bioanylitical business of SuNyx GmbH* (Germany) Qiagen NV (the Netherlands; QGEN) 8/1/05 8/8/05 $0.8 Qiagen paid $0.8M up front and could pay another $0.8M if certain milestones are reached for SuNyx, which has nanotechnology-based sample preparation technology Synthematix Inc.* Symyx Technologies Inc. (SMMX) 2/23/05 4/1/05 $13 Synthematix, which provides software systems for chemistry research, got $13M in cash and could get $4M more based on achievement of revenue targets for 2005 Syrrx Inc.* Takeda Pharmaceutical Co. Ltd. (Japan) 2/7/05 3/16/05 $270 Syrrx became a subsidiary named Takeda San Diego following the all-cash deal Tarpan Therapeutics Inc.* Manhattan 1/5/05 Pharmaceuticals Inc. (OTC BB:MHTT) ND Manhattan issued stock equal to 20% of the enlarged company to acquire Tarpan, which is developing dermatological therapeutics 184 4/4/05 Value (M)*** Terms/Details BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed TekCel* Magellan Biosciences* 5/16/05 5/16/05 ND Magellan acquired TekCel, which has sample-management and assay-automation systems for biomedical research Tianwei Times* (China) Qiagen NV (the Netherlands; QGEN) 6/13/05 6/13/05 $2 Tianwei supplies nucleic acid sample preparation consumables in China; it could earn another $2M in payments over two years Trace Genetics Inc.* DNAPrint Genomics Inc. (OTC BB:DNAP) 6/21/05 6/21/05 $25 Trace shareholders received 25M DNAP shares in the deal and options to purchase 5M additional shares at $0.02 each TransForm Pharmaceuticals Inc.* Johnson & Johnson 3/9/05 4/4/05 $230 J&J paid $230M in cash for TransForm, which was founded in 1999 and focuses on drug formulations Transkaryotic Therapies Inc. (TKTX) Shire Pharmaceuticals Group plc (UK) 4/21/05 7/27/05 $1.6B Shire paid $37 in cash for each TKT share, a premium of 44% to the four-week average before the deal was announced Certain assets of UroGene SA* (France) Laboratories Pierre Fabre (France) 1/24/05 1/24/05 ND UroGene sold its chemistry platform and two programs in cancer to Pierre Fabre as part of a plan to divest its assets Verigen AG* (Germany) Genzyme Corp. (GENZ) 2/8/05 2/8/05 $10 Verigen could get another $40M over six years based on achieving development and commercial milestones; Verigen has a cell therapy product for cartilage repair that is sold in Europe and Australia Vicuron Pharmaceuticals Inc. (MICU) Pfizer Inc. 6/16/05 9/14/05 $1.9B Pfizer paid $29.10 per share in cash, or $1.9B, a 74% premium to the 90-day price before the deal was disclosed Viventia Biotech Inc. (Canada; TSE:VBI) The Dan Group 1 1/14/05 12/23/05 ND The Dan Group, which already held 90% of the company following a recent investment, paid C$2.50 for each share it didn’t own; the company became private following the deal Drug Delivery business of West Pharmaceutical Services Inc. Archimedes Pharma Ltd.* (UK) 2/8/05 2/9/05 $7.1 Archimedes, formed by three former Shire Pharmaceuticals Group plc executives, paid $7.1M for the drug delivery assets; West also got 1 4% ownership in Archimedes and would get a 3% royalty on any sales from technology it contributed BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Value (M)*** Terms/Details 185 2005 Biotechnology Mergers And Acquisitions Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Value (M)*** Terms/Details Xcel Pharmaceuticals Inc.* Valeant Pharmaceuticals International (NYSE:VRX) 2/2/05 3/1/05 $280 Valeant paid $280M in cash to acquire the neurology company XenoTrans Ltd.* (Australia) Revivicor Inc.* 6/23/05 6/23/05 ND Revivicor purchased the assets and technology of XenoTrans, which was focused on xenotransplantation Xenova Group plc (UK; XNVA) (Bermuda) Celtic Pharma Group 6/24/05 9/1/05 £26.1 ($48) Celtic, a private equity firm, is paying up to £26.1M in notes, cash or a blend of each for Xenova; separately, Celtic licensed technology and provided a $20M loan facility Xtrana Inc. (OTC BB:XTRN) Alpha Innotech Corp.* 12/14/04 10/3/05 ND Xtrana shareholders own about 17% of the combined company following the reverse merger; they kept the Alpha Innotech name; the stock symbol changed to OTC BB:APNO Zeneus Holdings Ltd.* (UK) Cephalon Inc. (CEPH) 12/6/05 12/22/05 $360 Cephalon paid $360M in cash for Zeneus, which markets a number of oncology products in Europe Zymed Laboratories Inc.* Invitrogen Corp. (IVGN) 1/10/05 2/14/05 $60 Invitrogen paid $60M in cash to acquire the antibody manufacturer $2.2B Amgen intends to pay $2.2B in cash, or $22.50 per Abgenix share, and assume debt in the deal; they already are partnered on cancer antibodies $31 Regenera would own at least 52.2% of the combined firm, which would assume the Advanced Ocular Systems name and headquarters III. PENDING MERGERS AND ACQUISITIONS Abgenix Inc. (ABGX) Amgen Inc. (AMGN) 12/14/05 1Q:06 Advanced Ocular Systems Inc.* Regenera Ltd. (Australia; ASX: RGA) 10/31/05 4Q:05 Research products division of Ambion Inc.* Applied Biosystems Group (NYSE: ABI) 12/27/05 1Q:06 $273 ABG intends to pay $273M in cash for the division, which is a supplier of RNA-based reagents American Pharmaceutical Partners Inc. (APPX) American BioScience Inc.* 1 1/28/05 1H:06 $4.1B ABI already owns 64.4% of APP; APP would issue 86M additional shares, giving ABI 83.5% of the combined company; the combined company would change its name to Abraxis BioScience 186 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Berna Biotech Ltd. (Switzerland; SWX:BBIN) Crucell NV (the Netherlands; CRXL) 12/1/05 1Q:06 BCY LifeSciences Inc. (Canada; CDNX:BCY) Pipex Therapeutics Inc.* 10/21/05 ND Celliance (subsidiary of Serologicals Corp.; SERO) SeraCare Life Sciences Inc. (SRLS) 1 1/29/05 Chiron Corp. (CHIR) Novartis AG (Switzerland) Gastrotech Pharma A/S* (Denmark) DOR BioPharma Inc. (AMEX:DOR) Hapto Biotech Ltd.* (Israel) Value (M)*** Terms/Details CHF591 ($450) Crucell is offering CHF15.72 per Berna share in an all-stock deal; the combined company would operate in the Netherlands under the Crucell name; Novartis AG said on Dec. 19 it was considering making a bid for Berna ND They agreed to negotiate a potential merger under which Pipex would hold a majority position in the combined company; Pipex is providing BCY a $50,000 bridge loan over four months 1Q:06 $3.7 The deal would strengthen SeraCare’s position in molecular diagnostic reagents, diagnostic intermediates and substrates 10/31/05 1H:06 $5.1B Definitive agreement calls for Novartis to acquire the 58% of Chiron it doesn’t already own, or 1 13M shares, for $45 per share in cash; Chiron on Sept. 5 rejected Novartis’ earlier offer of $4.5 billion 1 1/2/05 1Q:06 $9 DOR intends to issue $9M in stock and could pay $30M more in cash or stock if certain milestones are reached Ortec 12/15/05 International Inc. (OTC BB:ORTN) 1Q:06 $5.6 Hapto shareholders would get 30.86M Ortec shares, and warrants to purchase 3M Ortec shares at 35 cents each HealthLinx Pty. Ltd.* (Australia) Cryptome Pharmaceuticals Ltd. (Australia; ASX:CRP) 1 1/16/05 1Q:06 A$6 ($4.4) Cryptome intends to issue A$6M in stock for HealthLinx, a company developing diagnostic products KuDOS Pharmaceuticals Ltd.* (UK) AstraZeneca plc (UK) 12/23/05 1Q:06 $210 Deal calls for AstraZeneca to pay $210M in cash; KuDOS is developing cancer drugs based on the inhibition of DNA repair Maui General Store Inc. (OTC BB:MAUG) Trinity BioGenetics Corp.* 12/13/05 1Q:06 ND Palmera Holdings Inc. subsidiary Trinity would own 91% of the combined company following the reverse merger Maxim Pharmaceuticals Inc. (MAXM) EpiCept Corp.* 9/6/05 1Q:06 ND EpiCept shareholders would get stock representing about 72% of the combined company; the merged firm would be valued at about $136M BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 187 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Value (M)*** Terms/Details Metaphore Pharmaceuticals Inc.* ActivBiotics Inc.* 12/14/05 1Q:06 ND Metaphore would become a wholly owned subsidiary of ActivBiotics under the definitive merger agreement Miikana Therapeutics Inc.* EntreMed Inc. (ENMD) 12/22/05 1Q:06 $21.2 EntreMed intends to issue 9.96M shares in the deal and may pay up to $18M more in stock or cash if certain clinical and regulatory milestones are met Molecular Molecular Pharmacology Pharmacology Ltd. (Australia; (USA) Ltd. unit of PharmaNet (OTC BB:MLPH) Group Ltd.; ASX:PNO) 12/5/05 1Q:06 $176 MPL USA intends to issue 88M shares to acquire MPL, a wholly owned division of PharmaNet Sahajanand Medical Technologies* (India) MIV Therapeutics Inc. (Canada; OTC BB:MIVT) 3/1 1/05 1Q:06 ND The merger would bring together products and drug-eluting technologies in coronary stents; Sahajanand’s stents are sold in more than 33 countries Shenzhen PG Biotech Co Ltd.* (China) Qiagen NV (the Netherlands; QGEN) 9/26/05 1H:06 $14.5 Qiagen intends to pay $14.5M in cash to acquire Shenzhen, a supplier of PCR-based molecular diagnostic kits in China Survac ApS* (Denmark) Merck KGaA (Germany) 1 1/21/05 4Q:05 €1 1 ($13) Survac is developing a technology to identify and modify peptides useful for therapeutic cancer vaccines (1 1/21) Targeted Molecules Corp.* Chromos Molecular Systems Inc. (Canada; TSE:CHR) 5/25/05 4Q:05 C$5 ($4) Chromos intends to issue about 20. 1M shares in the deal; TMC is developing two antibody product candidates; Chromos said in November a definitive agreement had been reached; TMC would own 26% of the merged company Xcyte Therapies Inc. (XCYT) Cyclacel Group plc* (UK) 12/15/05 1Q:06 ND Cyclacel shareholders would own about 80% percent of the combined company following the reverse merger III. TERMINATED MERGERS AND ACQUISITIONS Company To Be Acquired (Country; Symbol) Acquiring Company (Country; Symbol) Date Announced Termination Date Anosys Inc.* Chromos Molecular Systems Inc. (Canada; TSE:CHR) 3/15/05 4/1/05 188 Value (M)*** C$3.6 ($3) Terms/Details Chromos, while announcing it was restructuring its business, said negotiations on the Anosys acquisition had ended; details were not disclosed BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Mergers And Acquisitions (Continued) Company Acquired (Country; Symbol) Acquired By Or Merged With (Country; Symbol) Date Announced Date Completed Value (M)*** Terms/Details Cengent Therapeutics Inc.* Inncardio Inc. (OTC BB:INDO) 4/1/05 1 1/14/05 ND Cengent shareholders would have owned 45% of the combined company; Inncardio said there was a default under a credit line facility agreement Corgenix Medical Corp. (OTC BB:CONX) Genesis Bioventures Inc. (AMEX:GBI) 8/5/03 1/14/05 $8 Genesis planned to issue 1 4M shares in the deal; Corgenix terminated the deal due to a lack of a contingent financing and the passing of expiration dates IGI Inc. (AMEX:IG) Senetek plc (OTC BB:SNTKY) 10/27/04 4/6/05 ND Senetek called off merger discussions following several revisions to the proposed deal; the companies intend to collaborate on their respective technologies Osteotech Inc. (OSTE) Musculoskeletal Transplant Foundation 7/12/05 10/17/05 $107 MTF offered $6.25 per share in cash for Osteotech, which in August rejected the unsolicited proposal; MTF withdrew the offer in October Synt:em SA* (France) Sonus Pharmaceuticals Inc. (SNUS) 1 1/3/04 3/15/05 $12 Sonus decided to call off the merger, saying a review showed it would be best to operate as a stand-alone company at this time Notes: # This chart is intended to include not only mergers and acquisitions of entire businesses, but also of divisions or subsidiaries of those businesses, where appropriate. In general, it does not include acquisitions of single products or of manufacturing facilities. For those deals that were pending on Dec. 31, 2005, and for which the acquiring company was issuing stock, the value of the transaction was calculated based on the closing price prior to the first announcement. For stock-based deals that have been completed, the final value was calculated based on the closing price before the merger’s completion was announced. * Private companies are indicated with an asterisk. ** Conversions of non-U.S. currencies are calculated using the rate on the date the transaction closed, or for pending deals, on the date it was announced. ND = Not disclosed; N/A = Not applicable. Unless otherwise indicated, shares are traded on the Nasdaq exchange. AIM = Alternative Investment Market; AMEX = American Stock Exchange; ASX = Australian Stock Exchange; CDNX = Canadian Venture Exchange; CSE = Copenhagen Stock Exchange; FSE = Frankfurt Stock Exchange; LSE = London Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; PK = Pink Sheets; SSE = Stockholm Stock Exchange; SWX = Swiss Stock Exchange; TSE = Toronto Stock Exchange. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 189 2005 Biotech-Big Pharma Collaborations#: New Agreements Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Terms/Details (Date) Addex Ortho-McNeil Pharmaceuticals Pharmaceutical Inc. SA* (Switzerland) (unit of Johnson & Johnson) Collaboration to discover, develop and sell compounds that modulate allosterically GPCRs for treating various CNS diseases Addex gets an up-front fee and research funding for two years; it also could earn milestone and royalty payments (1/17) Adenosine Therapeutics LLC* Collaboration and option deal to further develop A2B adenosine receptor antagonists for Type II diabetes, asthma and other disorders Ortho-McNeil gets a one-year exclusive option to certain compounds and will fund a one-year research alliance; if the option is exercised Adenosine would get an option fee, research support and potential milestone and royalty payments (1/19) Affectis Mitsubishi Pharmaceuticals Pharma Corp. AG* (Germany) (Japan) Affectis will use its target validation technology and animal models in a deal to develop drugs for affective disorders Affectis (formerly Neuronova AG) will work on Mitsubishi targets in anxiety and depression; terms of the deal were not disclosed (2/7) Albany Molecular Research Inc. (AMRI) Eli Lilly and Co. AMRI will provide chemistry research on projects in undisclosed areas identified by Lilly Terms of the fee-for-service deal were not disclosed; the new deal continues a relationship between the companies that began in 1998 (2/8) Albany Molecular Research Inc. (AMRI) Alcon Research Ltd. AMRI will screen its natural product collections under a two-year deal to discover and develop ophthalmic drugs AMRI will get service and library-access fees, as well as potential milestone payments and sales royalties (1/7) Allergy Therapeutics plc (UK; LSE:AGY) Allerpharma Inc. (Canada) Allerpharma got rights to market AT’s four-shot allergy vaccine Pollinex Quattro in Canada They will collaborate on further development, and Allerpharma gets rights to sell AT’s existing ragweed allergy in Canada; AT gets up to $15M in milestone payments and royalties on sales (1/5) Alliance Pharmaceutical Corp. (OTC BB: ALLP) LEO Pharma A/S (Denmark) LEO plans to license rights to develop and sell Oxygent in Europe and Canada Alliance subsidiary PFC Therapeutics LLC is entitled to up-front, milestone and royalty payments, subject to completion of due diligence by LEO (1/3) Alnylam Medtronic Inc. Pharmaceuticals Inc. (ALNY) Collaboration to develop drug-device combinations incorporating RNAi therapeutics for treating neurodegenerative disorders If they enter product development after an initial program, Alnylam would receive an equity investment and could get additional payments, as well as milestones and royalties for each product developed (2/9) FIRST QUARTER 190 Ortho-McNeil Pharmaceutical Inc. (unit of Johnson & Johnson) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Ambit Biosciences Inc.* Bristol-Myers Squibb Co. Ambit will use its kinase platform to characterize the specificity of certain BMS compounds Terms of the deal were not disclosed (1/17) Ambit Biosciences Inc.* GlaxoSmithKline plc (UK) Ambit will use its platform to profile kinase target specificity of certain GSK compounds Terms of the deal were not disclosed (1/17) Ambit Biosciences Inc.* Pfizer Inc. Ambit will apply its Reverse Screening technology to identify and characterize protein targets of certain Pfizer compounds Terms of the deal were not disclosed (1/17) Amphora Discovery Corp.* Ortho-McNeil Pharmaceutical Inc. (unit of Johnson & Johnson) They entered a multiyear deal to discover and develop treatments for inflammatory diseases Ortho-McNeil gets exclusive rights to existing Amphora compounds as well as new ones discovered during the collaboration; Amphora gets a license fee, research funding and potential milestone and royalty payments (1/10) Argenta Discovery Ltd.* (UK) Novartis AG (Switzerland) Two-year drug discovery collaboration in the area of diabetes Up to 18 Argenta scientists will work on the Novartis program; terms of the deal were not disclosed (1/24) Ariad Medinol Ltd. Pharmaceuticals (Israel) Inc. (ARIA) Deal to develop stents and other devices to deliver Ariad’s mTOR inhibitor AP23573 in angioplasty procedures Ariad is eligible to receive license fees and milestone payments of up to $39.25M, if two products are developed, plus royalties on product sales (1/27) Avexa Ltd. (Australia; ASX:AVX) Shire Pharmaceuticals Group plc (UK) Avexa licensed rights to the HIV compound SPD754 worldwide except North America The deal includes reciprocal royalty provisions; Shire took an A$2M equity position in Avexa, and has an option to acquire 4M more shares following successful completion of ongoing Phase IIb trials (1/17) Axxam Srl* (Italy) CyBio AG (Germany) Deal to develop and sell technologies for drug discovery using automated luminescence screening systems They each will contribute technology to the effort; terms were not disclosed (2/8) Basilea Pharmaceutica AG (Switzerland; SWX:BSLN) Cilag AG International (unit of Johnson & Johnson) Worldwide, exclusive deal to develop and market ceftobiprole, Basilea’s Phase III broad-spectrum antibiotic Basilea will get up-front and milestone payments of up to $304M; it also would get double-digit royalties on sales (2/3) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 191 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) BioCurex Inc. (OTC BB: BOCX) Abbott Laboratories Abbott licensed RECAF technology, a cancer biomarker that may be useful in new diagnostic tests BioCurex gets up-front fees, development milestones and royalties on any sales; Abbott gets worldwide, semi-exclusive rights (3/29) BioDelivery Sciences International Inc. (BDSI) Sigma-Tau Group (Italy) BDSI will apply its Bioral nanocochleate delivery technology to formulate up to four Sigma-Tau compounds Sigma-Tau is buying $250,000 of BDSI stock at $4.25 per share share and up to $1.25M more if milestones are achieved; BDSI also would get royalties on sales (1/20) BioFocus plc (UK; AIM:BIO) Eli Lilly and Co. Deal to discover compounds that target nuclear hormone receptors The deal involves use of BioFocus’ highthroughput expertise; BioFocus will get research fees that increase as the program progresses (3/2) BioImage A/S* (Denmark) Boehringer Ingelheim GmbH (Germany) BI gained rights to use BioImage’s Redistribution technology in drug discovery research The technology is used for studying intracellular signaling events; terms of the deal were not disclosed (1/31) Biolex Inc.* Centocor Inc. (unit of Johnson & Johnson) Deal under which Biolex will manufacture and help advance certain Centocor proteins using the Biolex LEX System Biolex, which will advance up to 10 proteins, gets an up-front payment and potential milestones and royalties; it also gets funding over three years to support scale-up of parts of the system, and J&J will make an equity investment in Biolex’s next financing (3/21) Cangene Corp. (Canada; TSE:CNJ) Baxter Healthcare Corp. Baxter assumed exclusive rights to market Cangene’s WinRho SDF immune globulin product in the U.S. Baxter already markets the product for immune thrombocytopenic purpura in the UK and intends to launch it in 10 other European countries; terms were not disclosed (3/29) Cellzome Inc.* Ortho-McNeil Pharmaceutical Inc. (unit of Johnson & Johnson) Collaboration to identify new medicines for treating Alzheimer’s disease Cellzome is providing access to its AD technology in exchange for a technology access fee and research funding for two years, as well as potential milestone and royalty payments (3/16) Cenix Schering AG BioScience (Germany) GmbH* (Germany) Research service agreement to accelerate Schering’s target discovery and validation efforts Cenix will validate collections of candidate genes identified by Schering as possible therapeutic drug targets; terms were not disclosed (2/28) CepTor Corp. (OTC BB:CEPO) JCR got a 15-year license to market CepTor’s muscular dystrophy product Myodur in the Pacific Rim The deal entitles CepTor to equity payments, milestone payments and doubledigit royalties on sales in the Pacific Rim (3/2) 192 JCR Pharmaceuticals Co. Ltd. (Japan) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Cerep SA (France; Nouveau Marche:CERF) Sanofi Synthélabo Recherche (France) Cerep will synthesize thousands of compounds for Sanofi The companies also renewed a discovery deal signed in 1997 for 2005; terms were not disclosed (2/14) Cerus Corp. (CERS) and Baxter International Inc. BioOne Corp. (Japan) Letter of intent calls for BioOne to sell the Intercept Blood System for plasma in much of Asia Cerus gets $3M upon signing the letter of intent; the companies last year entered a a similar deal covering the system for platelets in Japan (1/5) ChemBridge Corp.* UCB Group SA (Belgium) ChemBridge will provide chemistry services to help UCB discovery efforts Further details and financial terms were not disclosed (3/2) Coley Pharmaceutical Group Inc.* Pfizer Inc. Worldwide deal to develop and sell Coley’s ProMune, a Toll-like receptor 9 agonist, for cancer indications Coley gets $50M up front and up to $455M more in milestone payments, plus royalties on any sales; Pfizer may invest up to $10M in Coley upon Coley’s initial public offering (3/24) Crucell NV (the Mitsubishi Pharma Netherlands; CRXL) Corp. (Japan) and DSM Biologics (the Netherlands) Mitsubishi got rights to use the PER.C6 cell line for producing certain recombinant therapeutic proteins Mitsubishi will make an up-front payment and pay annual maintenance fees; further terms were not disclosed (3/23) Crucell NV (the JCR Netherlands; CRXL) Pharmaceuticals and DSM Biologics Co. Ltd. (Japan) (the Netherlands) JCR got rights to use the PER.C6 cell line for producing certain recombinant therapeutic proteins JCR will make a research license payment and annual maintenance fees; further terms were not disclosed (3/10) Crucell NV (the F. Hoffmann-La Netherlands; CRXL) Roche Ltd. and DSM Biologics (Switzerland) (the Netherlands) Roche got a license to use the PER.C6 cell line for production of monoclonal antibody products and a specific undisclosed protein Roche will provide a research license payment, annual maintenance fees and research funding; further terms were not disclosed (2/16) Cyclacel Group plc* (UK) Altana Pharma AG (Germany) Cyclacel will use its expertise in cell division to identify molecular targets of specific Altana drug candidates Terms of the deal were not disclosed (3/16) Cyntellect Inc.* Daiichi Pharmaceutical Co. Ltd. (Japan) Daiichi will use Cyntellect’s high-throughput cell-imaging and cell-manipulation technologies in drug discovery Cyntellect will design and run LEAP cellbased assays against a Daiichi compound collection; terms of the deal were not disclosed (3/30) Second deal between the companies gave DePuy rights to autologous platelet releasate therapy The license excludes treatment of chronic wounds; also, DePuy’s existing license for spinal, orthopedic and neurosurgical applications will be converted to a nonexclusive license; terms were not disclosed (3/8) Cytomedix DePuy Spine Inc. Inc. (OTC BB:CYME) (unit of Johnson & Johnson) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 193 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Dendritic Nano- The Dow Technologies Chemical Co. Inc.* and Starpharma Holdings Ltd. (Australia; ASX:SPL) DNT and Starpharma acquired Dow’s patent portfolio in the field of dendrimers (nanostructures) Dow gained a significant equity stake in DNT; Starpharma, which already owned 42% of DNT, will make an additional equity investment in DNT in exchange for exclusive rights to polyvalent, dendrimer-based pharmaceutical applications (1/25) Diversa Corp. (DVSA) Merck & Co. Inc. Diversa will apply its MedEv platform in a collaboration to develop therapeutic antibodies for an undisclosed target Diversa gets an up-front payment and research funding; further terms were not disclosed (1/1 1) Eiffel Technologies Ltd. (Australia; ASX:EIF) Undisclosed U.S. company They signed a second deal in three months; Eiffel will use its re-engineering technology to formulate an asthma drug Eiffel will receive a $75,000 up-front payment for the two-month study; further licensing deals could ensue (2/28) EiRx Merck & Co. Inc. Therapeutics plc (Ireland; AIM:ERX) EiRx will perform research over three months to demonstrate its technology to Merck EiRx will use it siRNA delivery technology, which is used for validation of drug targets; terms were not disclosed (2/7) Entelos Inc.* Organon International (the Netherlands) They extended rheumatoid arthritis collaboration to develop and sell therapeutics directed at targets identified by Entelos They entered the deal after three years of research; Organon gets exclusive rights to the targets and access to Entelos research capabilities; Entelos gets co-promotion and co-commercialization rights (2/15) ESBATech AG* (Switzerland) Novartis Pharma AG (Switzerland) Collaboration for drug discovery in the area of receptor tyrosine kinase inhibitors Novartis gets nonexclusive access to ESBATech’s cellular high-throughput technology under undisclosed terms (3/31) Evotec OAI AG (Germany; FSE:EVT) Mitsubishi Pharma Corp. (Japan) Evotec will support the advancement of compound hit series for Mitsubishi drug targets Terms of the medicinal chemistry agreement were not disclosed (2/28) 4SC AG* (Germany) Sanwa Kagaku Kenkyusho Co. Ltd. (Japan) 4SC will apply its discovery platform to develop drug candidates against two specific targets from SKK 4SC gets research funding over several years and is eligible for research and clinical milestone payments, as well as royalties on any resulting sales (2/15) Galapagos Genomics NV* (the Netherlands) GlaxoSmithKline plc (UK) GSK exclusively licensed drug targets from Galapagos’ asthma and allergy program They also entered a three-year deal to discover further targets in asthma and inflammatory diseases; Galapagos gets an up-front payment, research funding and potential milestone payments (1/5) 194 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Galenea Corp.* Otsuka Pharmaceutical Co. Ltd. (Japan) Deal to discover drugs for treating central nervous system diseases Otsuka will make an equity investment and pay five years of R&D funding in exchange for rights to targets and drug candidates; Galenea also can get milestone and royalty payments and would have an option to participate in profit sharing (2/16) Gamida-Cell Ltd.* (Israel) Teva Pharmaceutical Industries Ltd. (Israel) Teva exercised an option to enter a joint venture to develop and sell StemEx for leukemia and lymphoma Teva will invest up to $25M in the joint venture; it held the option as part of an investment in Gamida-Cell in 2003 (2/16) GB Therapeutics Ltd.* (Canada) Chiesi Farmaceutici SpA (Italy) GB licensed Chiesi’s CHF1512, a methyl-ester of levodopa combined with carbidopa The product is registered in Italy; Chiesi gained an equity stake in GB; terms of the exclusive license to the Parkinson’s disease drug were not disclosed (1/27) GeneGo Inc.* GlaxoSmithKline plc (UK) GSK licensed use of the MetaBase biology and chemistry platform GSK will apply MetaBase to drug discovery efforts and integrate content with its internal informatics systems; terms were not disclosed (1/31) GeneGo Inc.* Altana Pharma AG (Germany) Altana licensed use of the MetaCore systems biology platform Terms of the deal were not disclosed (1/21) Gene Network Sciences* Johnson & Johnson Pharmaceutical Research & Development LLC GNS will provide pathway inference technology and data-driven computer models to J&J The technology will help determine pathways data for a J&J preclinical oncology compound; terms of the deal were not disclosed (3/7) Genentech Inc. (NYSE:DNA) Ipsen SA (France) Deal to develop sustainedrelease formulations of Genentech’s recombinant human growth hormone The alliance supplements an existing deal under which Ipsen markets NutropinAq in Europe and has rights elsewhere except North America and Japan; terms of the deal were not disclosed (3/21) Genfit SA* (France) Pierre Fabre Group (France) Three-year collaboration to develop a new family of compounds for cardiovascular and other diseases Genfit will get research fees and potential milestone and royalty payments; the deal is separate from their ongoing collaboration from 2001 (1/3) Genomatica Inc.* Kyowa Hakko Kogyo Co. Ltd. (Japan) Kyowa Hakko licensed Genomatica’s modeling and simulation platform Genomatica is entitled to license fees and milestone payments; the technology will be used for producing high-quality fine chemicals (1/5) Genome Express* (France) bioMerieux SA (France) Genome Express will carry out bacterial analyses for bioMerieux Terms of the deal were not disclosed (3/4) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 195 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Gen-Probe Inc. (GPRO) bioMerieux SA (France) bioMerieux exercised an option to develop diagnostic products for certain disease targets using Gen-Probe’s ribosomal RNA technologies Gen-Probe gets a $4.5M license fee, while bioMerieux retains options to develop diagnostics for other disease targets by paying up to $3M more by the end of 2006 (1/20) GenWay Biotech Inc.* Beckman Coulter Inc. BC got access to GenWay’s IgY microbead technology, which can be used in detecting biomarkers and drug targets The exclusive license agreement also provides a basis for future collaboration on development of GenWay’s IgY capture technology; terms were not disclosed (3/31) Geron Corp. (GERN) Cambrex Bio Science Walkersville Inc. Cambrex will develop and distribute cell lines that have been immortalized using Geron’s telomerase technology Geron gets an up-front license fee and royalties on any sales and retains all rights for the use of telomerized cells in therapeutic applications (1/1 1) Gilead Sciences Inc. (GILD) Japan Tobacco Inc. (Japan) Gilead got exclusive rights outside Japan to develop an HIV integrase inhibitor (JTK-303) JT gets $15M up front and up to $90M in milestone payments, as well as royalties on any sales; Gilead plans to start Phase I/II trials by mid-2005 (3/22) Helix Apotex Group BioPharma Corp. (Canada) (Canada; TSE:HBP) Helix will identify and characterize a lead formulation for Apotex’s topical therapeutic product line The work will be done by Helix subsidiary PharmaDerm Laboratories; terms were not disclosed (2/28) Helix BioMedix Inc. (OTC BB: HXBM) Smith & Nephew plc (UK) Smith & Nephew got a right of first offer to license rights to certain wound-related indications for the peptide HB50 Smith & Nephew will provide development input; terms of the deal were not disclosed (1/21) Human Metabolome Technologies Inc.* (Japan) Mitsubishi Pharma Corp. (Japan) Collaboration to find a biomarker for phospholipidosis, a lipid storage disorder HMT will apply its metabolome technology in the deal, terms of which were not disclosed (2/14) Iceland Genomics Corp.* (Iceland) Roche Diagnostics (Switzerland) Collaboration to analyze patient samples for discovery of cancer biomarkers IGC gets access to certain gene-expression data and support for further biological characterization of the samples in Iceland; terms of the deal were not disclosed (3/17) Icoria Inc. (ICOR) Syngenta Ltd. (Switzerland) Syngenta got exclusive rights to develop 30 Icoria compounds believed to be active fungal inhibitors Syngenta will evaluate the compounds over 18 months, then could develop them in agricultural, human and other applications; Icora gets an up-front payment and could receive milestone and royalty payments (2/28) 196 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) ImClone Systems Inc. (IMCL) Pharma Co. (Country) Centocor Inc. (unit of Johnson & Johnson) Type/Product Area Term/Details (Date) ImClone licensed patents covering various aspects of antibody technology and uses of EGFR antibodies The license relates to ImClone’s approved product Erbitux and its investigational drug IMC-1 1F8; terms were not disclosed (1/26) Infinity Johnson & Johnson Pharmaceuticals Pharmaceutical Inc.* Research and Development LLC J&J got nonexclusive access to Infinity’s compound collection to identify drug leads Infinity received an undisclosed up-front fee and an equity investment (1/6) Infinity Novartis AG Pharmaceuticals (Switzerland) Inc.* Two-year deal to design small molecules to be synthesized by Infinity using its chemical technology platform Infinity received an equity investment and is expected to receive more than $10M in additional fees; each company can use the resulting compound collection in its own discovery efforts (1/5) Inpharmatica Ltd.* (UK) Pfizer Inc. Pfizer gained access to parts of Inpharmatica’s PharmaCarta platform The deal for target-selection technology is in addition to Pfizer’s Biopendium subscription; terms were not disclosed (1/25) Intercell AG (Austria; ATX:ICLL) Biological E. Ltd. (India) Deal under which Biological E. will manufacture and sell Intercell’s Japanese encephalitis vaccine in Asia The companies said they intend to work together in the future on other vaccines; terms were not disclosed (3/18) Ionix Reckitt Benckiser Pharmaceuticals Healthcare (UK) Ltd.* (UK) Collaboration on Ionix’s IX-1003 for post-operative pain and the preclinical products IX-1004 and IX-1005 for pain and opiate addiction All three products are based on intranasal delivery of RBH’s buprenorphine; Ionix is eligible for milestone and royalty payments and retains an option to co-promote IX1003 in the U.S. (2/28) Jerini AG* (Germany) Alcon Research Ltd. Multitarget collaboration to develop drugs for ophthalmology indications Jerini gets up-front and license fees as well as personnel funding, along with potential milestone and royalty payments (1/19) Juvantia Pharma Ltd.* (Finland) Alcon Research Ltd. Deal giving Alcon access to Juvantia compounds, which it will evaluate for treating ophthalmic diseases Alcon has the option to enter into a development and license agreement; terms of the deal were not disclosed (1/13) LifeSpan BioSciences Inc.* Pfizer Inc. Deal to develop an automated pathology system for evaluation of tissue specimens in preclinical studies The system developed by LifeSpan uses enhanced image capture and artificial intelligence computer analysis software; terms were not disclosed (3/3) Deal under which Locus will apply its molecular fragment technology focused on protein kinases Locus will design for Scios new chemical classes of protein kinase inhibitors under undisclosed terms (3/14) Locus Scios Inc. Pharmaceuticals (unit of Johnson Inc.* & Johnson) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 197 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) MAT Biotech* (France) Laboratoires Servier (France) Collaboration to develop antibody products for various cancers MAT’s anti-ferritine monoclonal antibody AMB8LK will be coupled to a cytotoxic molecule from Servier; terms were not disclosed (1/20) Medicago Inc.* (Canada) Bayer CropScience AG (Germany) Deal to assess the feasibility of using Medicago technology for producing an undisclosed human therapeutic protein The deal involves the Proficia Protein Technology, which entails use of alfalfa plants; terms of the deal were not disclosed (1/31) MedImmune Inc. (MEDI) Abbott Laboratories Abbott will market Numax, MedImmune’s anti-RSV monoclonal antibody in Phase III trials, outside the U.S. Abbott also will continue to market Synagis under the amended deal; MedImmune has the option to co-promote Numax in up to seven countries outside the U.S.; it retained rights in the U.S. (2/28) Millennium UCB Pharma Pharmaceuticals (Belgium) Inc. (MLNM) Deal to develop and sell antibodies generated from two Millennium targets: a costimulatory molecule and a chemokine receptor UCB will be responsible for development and costs through Phase II trials; Millennium is entitled to milestone payments, and retains the option to co-develop and cocommercialize products under a cost- and profit-sharing arrangement (1/25) Morphochem AG* (Germany) Alcon Research Ltd. Collaboration to develop small-molecule drugs against ophthalmic targets Morphochem will apply its MolMind technology to make libraries for certain Alcon targets in return for research payments and potential milestones and royalties; Alcon gets rights to any resulting products for ophthalmic and nasal applications (1/10) MorphoSys AG (Germany; FSE:MOR) Boehringer Ingelheim GmbH (Germany) An expanded collaboration gives BI an option to several exclusive licenses on new therapeutic antibody programs They already are developing two antibody programs; BI also got access to MorphoSys’ HuCAL Gold library; MorphoSys gets a technology access fee, annual license fees and optional R&D funding over five years, as well as potential milestones and royalties (3/17) NascaCell IP GmbH* (Germany) Boehringer Ingelheim GmbH (Germany) Collaboration on aptamerbased target validation and drug discovery NascaCell will provide BI custom aptamers for therapeutic targets; terms were not disclosed (2/16) Nektar Therapeutics (NKTR) Bayer HealthCare AG (Germany) Collaboration to develop an inhalable powder formulation of a novel form of ciprofloxacin for chronic lung infections Nektar, which will develop the powder and inhalation system, will receive funding for preclinical development, as well as potential milestone and royalty payments (1/25) 198 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) NeoPharm Inc. (NEOL) Nippon Kayaku Co. Ltd. (Japan) Nippon Kayaku got exclusive Japanese rights to IL13PE38QQR, a drug in trials for glioblastoma multiforme NeoPharm gets $2M up front and can earn $6M tied to approval in Japan; it also would be entitled to royalty and milestone payments based on sales (1/4) Neose Technologies Inc. (NTEC) BioGeneriX AG (Germany; part of the Ratiopharm Group) Three-month option deal to evaluate application of Neose’s GlycoPEGylation technology to a marketed therapeutic protein Neose will get initial payments; if a license deal is signed, Neose would get additional up-front and research payments and could get up to $61.5M in milestone payments, as well as royalties on product sales (1/28) New River Shire Pharmaceuticals Pharmaceutical Inc. (NRPH) Group plc (UK) Collaboration covering New River’s Phase III ADHD compound, NRP104; other indications also are covered New River gets $50 up front and would get $50M upon acceptance of an NDA filing, up to $300M in milestones related to FDAapproved product labeling and $100M if sales targets are hit; New River has a 25% co-promotion right in the U.S. (1/31) Novavax Inc. (NVAX) Ranbaxy Laboratories Inc. (India) Deal to evaluate a transdermal product formulated using Novavax’s micellar nanoparticle technology Novavax will get funding to complete a proof-of-concept study, which could be followed by a commercialization and development agreement (3/16) Osel Inc.* Miyarisan Pharmaceutical Co. Ltd. (Japan) Osel gained exclusive rights in North America and Europe to MIYA-BM The oral product is approved in Japan for treating antibiotic-induced gastrointestinal disorders; terms of the deal were not disclosed (3/2) Oxford BioMedica plc (UK; LSE:OXB) Undisclosed company The company gained use of Oxford’s LentiVector genedelivery system for research activities Oxford gets an up-front license payment and an annual maintenance fee; terms were not disclosed (2/1) Oxford Genome Sciences Ltd.* (UK) Bayer HealthCare AG (Germany) Oxford will evaluate candidate biomarkers that may have applications in breast cancer Oxford gets funding for the program under which it will apply proteomics technologies, and potential milestone payments (3/16) Pepscan Systems Solvay BV* and Pharmaceuticals ServiceXS* (both (Belgium) of the Netherlands) The companies will identify novel peptide substrates for a series of Solvay proteases Terms of the research agreement for the de-orphanization of proteases were not disclosed (3/8) Perlegen Sciences Inc.* Perlegen will conduct a high-density whole-genome association study for an undisclosed trait of interest Perlegen will genotype SNPs for the trait of interest and compare them to controls; terms of the deal were not disclosed (1/24) AstraZeneca plc (UK) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 199 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Perlegen Sciences Inc.* Johnson & Johnson Pharmaceutical Research and Development LLC Pharmacogenomics deal to identify genetic markers for patient response to a J&J compound Perlegen will genotype single nucleotide polymorphisms and analyze results in the deal, terms of which were not disclosed (1/1 1) PharmaDesign Inc.* (Japan) Merck & Co. Inc. Merck licensed a GPCR peptide ligand library designed by PDI Merck made the deal with PDI representative Summit Pharmaceutical International Corp.; terms were not disclosed (2/2) Power3 Medical Products Inc. (OTC BB:PWRM) New Horizons Diagnostics Corp. Collaboration to develop antibody-based diagnostics for neurodegenerative diseases The work will involve protein biomarkers from Power3; terms of the deal were not disclosed (3/28) Procyon Biopharma Inc. (Canada; TSE:PBP) Medicorp Inc. (Canada) Medicorp got exclusive rights to develop and sell PSP94-based test kits Medicorp will fund future development; they will share revenues from sales of test kits and from sublicensing deals (3/2) Quark Biotech Inc.* Sanwa Kagaku Kenkyusho Co. Ltd. (Japan) Sanwa gained rights in Asia to Quark’s Phase II compound BT16 for treating dyslipidemia Quark gets an up-front payment along with potential milestone and royalty payments (2/8) Rigel Pfizer Inc. Pharmaceuticals Inc. (RIGL) Deal to develop products for allergic asthma and other respiratory diseases based on Rigel’s preclinical compounds that inhibit IgE receptor signaling in mast cells Rigel gets an up-front payment along with potential milestone and royalty payments; Pfizer will make an equity investment in Rigel and be responsible for worldwide development and commercialization (1/20) Sangamo BioSciences Inc. (SGMO) Pfizer will assess Sangamo’s zinc finger DNA-binding protein technology for use in mammalian cell-based protein pharmaceutical production Pfizer will fund research at Sangamo, which will generate cell lines and vector systems; terms were not disclosed (1/5) Savient Ferring Holding Pharmaceuticals SA (Switzerland) Inc. (SVNT) They entered a co-promotion deal on Nuflexxa as part of Savient’s divestiture of its global biologics manufacturing business to Ferring Savient will establish a sales force for the co-promotion effort and get 50% of the global revenue from the approved sodium hyaluronate product above certain revenue thresholds; Ferring is paying $80M in cash over two years for the manufacturing business (3/23) Sention Inc.* Deal to develop a family of Merck compounds known as mGluR5 antagonists for treating mental retardation Sention gets access to preclinical candidates, which it will develop; it also can develop the drugs for Down syndrome and has an option in Huntington’s disease (1/19) 200 Pfizer Inc. Merck & Co. Inc. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Serenex Inc.* GlaxoSmithKline plc (UK) Serenex will use its Proteome Mining technology to provide information on compounds in development at GSK GSK scientists worldwide can submit compounds to Serenex for profiling against specific tissues and cell lines; terms of the deal were not disclosed (1/1 1) Serono SA (Switzerland; NYSE:SRA) Rosetta Biosoftware (unit of Merck & Co. Inc.) Serono licensed use of the Rosetta Resolver system Serono gets rights to the gene-expression data analysis system under undisclosed terms (2/28) SurroMed Inc.* PPD Inc. PPD is acquiring about all of the assets related to SurroMed’s biomarker business PPD will surrender for cancellation its shares of SurroMed preferred stock, will assume $3.4M of liabilities under capital leases and certain other liabilities related to the biomarker business and will guarantee repayment of a portion of a SurroMed bank loan up to $1.5M (1/17) TaiGen Procter & Gamble Biotechnology Pharmaceuticals Co. Ltd.* (Taiwan) Deal to further develop and sell P&G’s non-flourinated quinolone antibiotic TaiGen will develop the product through Phase II, after which they may seek a partner; TaiGen gets rights in China, Taiwan, Korea and certain other countries (1/5) Tepnel Life Sciences plc (UK; AIM:TED) Boehringer Ingelheim GmbH (Germany) BI will evlauate murine monoclonal antibodies generated by Tepnel subsidiary Diaclone Research Tepnel retains research and diagnostic rights to antibodies not developed as therapeutics by BI; terms were not disclosed (2/2) Theravance Inc. (THRX) GlaxoSmithKline plc (UK) GSK exercised its option to license Theravance’s inhaled bifunctional, muscarinic antagonist/beta2 agonist program Theravance could get up to $252M in upfront and milestone payments, if the program has both single-agent and combination products; it is the third respiratory program GSK licensed from Theravance (3/21) TorreyPines Therapeutics Inc.* Eisai Co. Ltd. (Japan) They entered a research agreement involving drug discovery for Alzheimer’s disease Eisai has exclusive rights of first negotiation for validated compounds discovered through the research; development deals could follow (3/18) Transport GlaxoSmithKline Pharmaceuticals plc (UK) Inc.* Collaboration covering Transport’s iontophoretic device/drug system for the delivery of the cold-sore drug acyclovir Transport gets an up-front license fee along with potential milestone and royalty payments and some funding for upcoming Phase III trials; GSK gets exclusive rights in Europe, Australia, Latin America and South Africa (1/27) ViroLogic Inc. (VLGC) ViroLogic will use its HIV resistance testing technology to support GSK programs GSK will use ViroLogic’s assays across its virology portfolio under the three-year, $7.5M deal (2/3) GlaxoSmithKline plc (UK) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 201 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) VirtualScopics LLC* Wyeth Pharmaceuticals VirtualScopics will provide analytical and other imaging services to Wyeth The services will be used in a Phase I trial of a product being studied for muscle wasting conditions; terms were not disclosed (3/14) Xcellsyz Ltd.* (UK) Cambrex Bio Science Walkersville Inc. Cambrex purchased conditionally immortalized cell lines from Xcellsyz Terms of the deal were not disclosed (1/18) Xencor Inc.* F. Hoffmann-La Roche Ltd. (Switzerland) Deal under which Roche will use Xencor’s XmAb technology on a Roche antibody against a cancer target Xencor will receive technology access and license fees and is eligible to receive additional license fees along with milestone and royalty payments (1/12) Xencor Inc.* Chugai Pharmaceuticals Co. Ltd. (Japan) Deal under which Chugai will use Xencor’s XmAb technology on one of its antibodies against a cancer target Xencor will receive technology access and license fees, and is eligible to receive additional license fees along with milestone and royalty payments (1/10) YM BioSciences Inc. (Canada; TSE:YM) Shin Poong Pharmaceutical Co. (South Korea) Collaboration to expand development of YM’s tesmilifene into gastric cancer Shin Poong will fund development and provide undisclosed up-front and potential milestone and royalty payments, and will launch a bridging study in breast cancer in Asia (1/31) Three-year expansion of an alliance to develop gap junction-modifying drugs for cardiovascular diseases The alliance followed a 2003 license deal for the co-development of ZP123, a drug being developed for arrhythmias; they now will work on other compounds, and Wyeth got rights to evaluate Zealand’s compound library; terms were not disclosed (3/4) Zealand Wyeth Pharmaceuticals Pharmaceuticals A/S* (Denmark) SECOND QUARTER AbGenomics Corp.* (Taiwan) Boehringer Ingelheim International GmbH (Germany) BI got worldwide rights to AbGenomics’ antibody 168, which is targeted to a range of immune-related diseases AbGenomics kept an option to co-promote resulting products in certain Asian countries; terms of the deal were not disclosed (6/6) Acologix Inc.* Toray Industries Inc. (Japan) Acologix got rights to develop and sell Toray’s TRK-820 in North America, and co-development rights in Europe TRK-820 is a selective kappa opioid receptor agonist that has completed Phase II trials in uremic pruritus; terms of the deal were not disclosed (6/16) Affymetrix Inc. (AFFX) bioMerieux SA (France) bioMerieux gained long-term and comprehensive access to Affymetrix’s GeneChip technology bioMerieux will use the technology for in vitro diagnostic tests for breast cancer; it also got an option to expand the deal into other cancer areas; terms were not disclosed (4/5) 202 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Alimentary Health Ltd.* (Ireland) Mead Johnson Nutritionals (unit of Bristol-Myers Squibb Co.) Research and cross-licensing deal covering nutritional applications of novel ingredient technologies for infants and children Each will contribute intellectual property to the research, and they will jointly fund development programs (4/28) Alliance Pharmaceutical Corp. (OTC BB: ALLP) Beijing Double-Crane Pharmaceutical Co. Ltd. (China) They finalized a deal covering the development and sales of Alliance’s Oxygent in China Alliance will get up-front fees and is eligible for milestone and royalty payments (5/16) Anadys Novartis Pharma Pharmaceuticals AG (Switzerland) Inc. (ANDS) Exclusive deal to develop ANA975 and additional Tolllike receptor 7 oral prodrugs for hepatitis B and C and possibly other infectious diseases Anadys gets an initial license payment of $20M and up to $550 million in regulatory and commercial milestone payments; Anadys also has an option to retain 35% of profits in the U.S. by contributing 35% of costs; otherwise it would get royalties on any resulting sales (6/2) Ark Therapeutics Group plc* (UK; LSE:AKT) Boehringer Ingelheim International GmbH (Germany) BI got rights to use Ark renin-angiotensin system technologies in its products Ark gets an up-front payment and could receive milestone payments and royalties on sales of cardiovascular products covered by its patents (4/1) Arrow Therapeutics Ltd.* (UK) Novartis Pharma AG (Switzerland) Collaboration to develop and market Arrow’s smallmolecule inhibitor A60444 for respiratory syncytial virus Arrow gets a $10M up-front payment and up to $217M in milestone payments, as well as royalties on resulting sales; Novartis also gets rights to back-up compounds and the right of first negotiation on other compounds (6/29) Aureus Pharma* (France) Sanofi-Aventis Group (France) Sanofi became the first customer for Aureus’ AurSCOPEIon Channel database The deal extends an existing collaboration covering other databases; terms were not disclosed (6/9) Avanir Novartis AG Pharmaceuticals (Switzerland) Inc. (AMEX:AVN) Worldwide deal to develop small-molecule drugs targeting macrophage migration inhibitory factor for treating inflammatory diseases Avanir is eligible to receive more than $200M in up-front and development, regulatory and sales milestone payments, and gets up to $2.5M per year for four years in research payments; it also would get royalties on sales (4/28) BioMarin Pharmaceutical Inc. (BMRN) BioMarin licensed tetrahydrobiopterin (6R-BH4) to treat the endothelial dysfunction that causes vascular complications in various diseases BioMarin previously licensed rights to the drug for use in genetic diseases, including phenylketonuria; Daiichi gets an up-front payment, development milestones for up to two indications, and royalties on any sales (5/5) Daiichi Suntory Pharma Co. Ltd. (Japan) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 203 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) BioXell SpA* (Italy) Merck & Co. Inc. Merck got exclusive rights to develop TREM-related therapeutic and diagnostic products; TREM is Triggering Receptors Expressed on Myeloid Cells BioXell gets an up-front payment and up to $150M in milestone payments, including $55.5M for successful development of the first product for the first indication; it also would get royalties on any sales (5/23) Cangen Biotechnologies Inc.* Olympus Corp. (Japan) Deal to develop a hybrid DNAbased and protein-based diagnostic test for lung cancer Cangen gets access to Olympus’ microarray technology in the deal, terms of which were not disclosed (5/25) Caprion Wyeth Pharmaceuticals Inc.* (Canada) They expanded an existing deal to include two clinical programs under way at Wyeth The focus is on discovery and development of protein biomarkers from Phase II trials in asthma and renal-cell carcinoma; terms of the deal were not disclosed (6/28) Cellzome Inc.* Ortho-McNeil Pharmaceutical Inc. (unit of Johnson & Johnson) Ortho exercised its option to develop Cellzome’s Gamma Secretase Modulator program The license stems from a March 2005 deal in Alzheimer’s disease; Cellzome gets an additional technology access fee and continued research funding, as well as potential milestone and royalty payments (5/23) Cerus Corp. (CERS) and Baxter International Inc. BioOne Corp. (Japan) Definitive agreement calls for BioOne to commercialize the Intercept Blood System for plasma in much of Asia Cerus already received $3M when a letter of intent was signed in January; potential up-front and milestone payments total $33M in cash and BioOne equity; Cerus also would get royalties on sales in the covered countries (6/6) ChemGenex Stragen Pharma Pharmaceuticals SA (Switzerland) Ltd. (Australia; CXSP) Collaboration to accelerate the clinical development of ChemGenex’s Phase II cancer drug Ceflatonin Stragen brings manufacturing and marketing expertise to the deal and would get 51% of profits in Europe; ChemGenex has product responsibility in North America and the Asia-Pacific region (6/27) Chromos Molecular Systems Inc. (Canada; TSE:CHR) Pfizer Inc. Pfizer got rights to use the ACE System to develop cell lines for research, development and manufacturing purposes The deal represents an expansion of a December 2004 deal under which Chromos is using the system to engineer cell lines to express a Pfizer protein; terms were not disclosed (5/30) Ciphergen Biosystems Inc. (CIPH) Bayer Pharmaceuticals Corp. Collaboration to identify biomarkers and develop an assay that may be used in a clinical trial in cancer Ciphergen will analyze patient samples from Phase II trials as part of the deal; it is entitled to up-front and milestone payments from Bayer (6/27) Codexis Inc.* Matrix Laboratories (India) Codexis will apply its reengineering technology to develop a process for an active pharmaceutical ingredient Codexis gets R&D funding along with potential milestone payments and royalties on any sales; Matrix gets exclusive rights to the process (6/15) 204 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Codexis Inc.* Bristol-Myers Squibb Co. Deal to improve biocatalyst productivity for an undisclosed product candidate from BMS Codexis gets research funding and a potential milestone payment; BMS may opt at that point to fund further research, which involves Codexis’ re-engineering platform (5/24) Collegium Pharmaceutical Inc.* URL/Mutual Pharmaceutical Co. Deal to develop and sell an undisclosed product Collegium will do early work on the compound, then transfer responsibilities to URL; Collegium is entitled to milestone and royalty payments (4/20) ComGenex Inc. (Hungary) Fournier Pharma (France) Collaboration under which ComGenex will provide exclusive chemistry services to Fournier for three years Fournier extended an initial 16-month project into the multiyear collaboration, terms of which were not disclosed (5/17) Compugen Ltd. (Israel; CGEN) Ortho-Clinical Diagnostics Inc. (unit of Johnson & Johnson) Deal to develop diagnostic products based on biomarkers discovered by Compugen; Ortho initially can develop up to nine biomarkers Ortho gets worldwide rights to resulting products; Compugen is entitled to license fees and milestone payments for each biomarker, as well as royalties on any sales (6/8) Compugen Ltd. (Israel; CGEN) Novartis AG (Switzerland) Compugen will develop a platform for research and analysis of biological data on biological interaction networks Novartis will make a one-time payment for the information and get sole rights to the project results; Compugen retains rights to the research and discovery systems developed through the collaboration (4/19) Conforma Therapeutics Corp.* Sumitomo Pharmaceutical Co. Ltd. (Japan) Conforma got exclusive rights in North America and Europe to the cancer drug Amrubicin The synthetic anthracycline agent is marketed in Japan as Calsed; terms of the deal were not disclosed (6/29) Cornerstone BioPharma Inc.* Lupin Ltd. (India) Collaboration to develop a drug delivery system for an anti-infective product Lupin gets up to $10.5M in milestone and other payments and royalties on any sales; Cornerstone has marketing rights in the U.S. (5/9) Correlogic Systems Inc.* Quest Diagnostics Inc. Correlogic received an equity investment; further terms were not disclosed (6/9) Cougar Biotechnology Inc.* LEO Pharma A/S (Denmark) Quest got an option to commercialize certain diagnostic tests Cougar got exclusive rights to seocalcitol (EB1089), a synthetic analogue of vitamin D with applications in cancer Crucell NV (the Netherlands; CRXL) Ferring Pharmaceuticals A/S (Denmark) Ferring got rights to use the PER.C6 cell line in the field of women’s health care BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 LEO gets an up-front payment and is entitled to milestone and royalty payments (6/28) The deal includes Crucell’s allied contract manufacturer DSM Biologics; terms were not disclosed (5/25) 205 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Cyntellect Inc.* Sigma-Aldrich Corp. Sigma-Aldrich got exclusive, worldwide rights to commercialize Cyntellect’s Cell Xpress service Cyntellect got a multimillion-dollar equity investment, and will get royalties on sales; Sigma-Aldrich also will pay for internal use of Cyntellect’s LEAP technology (4/27) Cypress Bioscience Inc. (CYPB) NV Organon (the Netherlands) Deal to combine expertise to develop a treatment for obstructive sleep apnea involving mirtazapine-based drugs and regimens They initially will share costs; Cypress would have co-commercialization rights in North America, and get royalties on sales elsewhere (6/29) Cytogen Corp. (CYTO) The Dow Chemical Co. Cytogen and Dowpharma are collaborating to create a targeted product for treating prostate and other cancers Dow technology will be used to radiolabel Cytogen’s PSMA antibody (7E1 1); the deal extends an existing agreement; terms were not disclosed (5/10) Depomed Inc. (DEPO) Boehringer Ingelheim Pharmaceuticals Inc. (Germany) Depomed will develop a controlled-release formulation of an undisclosed compound for BI Depomed will apply its Gastric Retention technology to the BI compound; a license agreement could follow (4/28) Diatos SA* (France) Servier (France) Deal to apply Diatos’ Vectocell technology to a small-molecule cancer candidate from Servier Servier will fund work at Diatos and gets an option to license resulting technology (5/17) Diversa Corp. (DVSA) Merck & Co. Inc. They expanded a deal signed in January focused on Diversa’s MedEv antibody evolution platform Diversa gets an additional up-front payment and research funding and is entitled to milestone and royalty payments upon successful development of antibodies (6/20) Elixir Bristol-Myers Pharmaceuticals Squibb Co. Inc.* Elixir got exclusive rights to BMS’s growth hormone secretagogue BMS-604992 and five related compounds BMS gets an up-front license fee comprised of cash and stock and is entitled to milestone and royalty payments; the program is at the preclinical stage (4/28) EraGen Biosciences Inc.* Bayer HealthCare LLC Bayer Diagnostics got exclusive rights to Eragen’s MultiCode-PLx System for use in cystic fibrosis Bayer also got rights to a create assays for other disease states; MultiCode-PLx is a high-throughput genotyping system; terms of the deal were not disclosed (5/18) Exelixis Inc. (EXEL) Helsinn Healthcare SA (Switzerland) Helsinn gained rights to develop the Phase III cancer drug XL1 19 (becatecarin) Exelixis gets $4M up front and up to $21M in milestone payments; Helsinn will pay Phase III costs; Exelixis is entitled to royalties and milestones on sales and retained an option to reacquire rights in the U.S. (6/10) 206 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) ExonHit Therapeutics SA* (France) Pharma Co. (Country) Allergan Inc. Type/Product Area Term/Details (Date) They extended deal from 2003 to develop drugs for neurodegenerative diseases, pain and ophthalmology ExonHit got a $2M payment and continues to receive R&D support; it also is entitled to milestone and royalty payments and has certain co-development and co-commercialization options (5/17) Fabre-Kramer NV Organon Pharmaceuticals (the Netherlands) Inc.* Fabre-Kramer reacquired all rights to the depression drug Gepirone ER, which failed to gain FDA approval in 2004 Organon would receive a milestone payment upon FDA approval and royalties on any sales; Phase III trials are ongoing (6/15) 454 Life Sciences (majority-owned by CuraGen Corp.; CRGN) F. Hoffmann-La Roche Ltd. (Switzerland) Exclusive five-year deal for sales and distribution of 454’s nanotechnology-based genome-sequencing systems 454 will get up to $62M in license fees, milestones related to instrument releases, minimum royalties and research funding; it also would get royalties on sales (5/12) 4SC AG* (Germany) Schwarz Pharma AG (Germany) Collaboration to develop hits against targets that they identified in a pilot project 4SC will use its technologies to develop pharmaceutical leads; 4SC gets research funding and is entitled to milestone payments and revenue sharing (4/5) Fulcrum Pharma plc (UK; AIM:FUL) Syngenta Biopharma (Switzerland) Fulcrum will provide development services for Syngenta The focus is on advancing Syngenta projects toward clinical development; terms of the deal were not disclosed (5/18) Genedata AG* (Switzerland) Novartis Institute Collaboration to advance for Tropical research in infectious and Diseases (Singapore) parasitic diseases Genedata’s Phylosopher technology will serve as a management system for data integration; terms were not disclosed (6/29) GeneGo Inc.* Procter & Gamble Pharmaceuticals Inc. P&G licensed MetaCore and MetaBase technologies from GeneGo The products are used in life science research; terms of the deal were not disclosed (5/9) GeneGo Inc.* NV Organon (the Netherlands) Organon licensed GeneGo’s MetaCore platform for mining high-throughput experimental data Organon will use MetaCore in preclinical research across various therapeutic areas (4/19) Generex Biotechnology Corp. (Canada; GNBT) Stallergenes SA (France) Deal to design and test Ii-Key/allergen epitope hybrid peptides for treating asthma and allergic reactions Generex subsidiary Antigen Express Inc. will work with Stallergenes on the project; terms of the deal were not disclosed (6/22) Haptogen Ltd.* (UK) DaeWoong Pharmaceutical Co. Ltd. (South Korea) Collaboration to progress the clinical development of antibody therapeutics targeted to bacterial infections They will combine Haptogen’s discovery approach with the formulation, manufacturing and marketing expertise of DaeWoong; terms were not disclosed (5/17) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 207 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Human Metabolome Technologies Inc.* (Japan) Agilent Technologies Inc. Collaboration to develop a set of metabolome analysis tools for use in drug discovery They plan to integrate HMT’s biochemical assays with Agilent’s capillary electrophoresis and mass spectrometry technology to profile and identify metabolic markers (6/20) Hybridon Inc. (AMEX:HBY) Novartis Pharma AG (Switzerland) Collaboration to discover and develop Toll-like receptor 9 drugs targeting asthma and allergy First they will evaluate immune modulatory oligonucleotide candidates; Hybridon then could earn up-front license fees along with milestone payments that could total $136M, as well as royalties on sales (6/1) Inovio Biomedical Corp. (AMEX:INO) Merck & Co. Inc. Merck exercised an option for a nonexclusive license to an additional antigen to be used with Inovio’s MedPulser DNA Delivery System Inovio gets an option fee and remains eligible for milestone and royalty payments; Merck now has licensed three antigens under their 2004 license agreement (5/12) Inpharmatica Ltd.* (UK) Daiichi Pharmaceutical Co. Ltd. (Japan) Daiichi licensed Inpharmatica’s Admensa Interactive technology The technology is a suite of predictive ADME models and compound-prioritization tools; terms were not disclosed (6/6) Intra-Cellular Therapies Inc.* Bristol-Myers Squibb Co. ITI got worldwide rights to a family of preclinical compounds targeting central nervous system diseases BMS receives an undisclosed license fee up front and potential milestone and royalty payments (6/1) Isis Pfizer Inc. Pharmacueticals Inc. (ISIS) Deal to identify secondgeneration antisense drugs for treating ophthalmic disease Isis gets a $1M technology access fee and research funding and is eligible to receive milestone and royalty payments (5/24) Kiadis BV* (the Netherlands) NV Organon (the Netherlands; unit of Akzo Nobel) Deal to evaluate Kiadis’ BioSelect screening technology in Organon’s reproductive medicine discovery program Kiadis intends to deliver novel active compounds against the target provided by Organon; terms of the deal were not disclosed (5/25) KeyNeurotek AG* (Germany) Bayer Healthcare AG (Germany) KeyNeurotek got exclusive rights to the traumatic brain injury compound BAY 38-7271 KeyNeurotek will continue development and would market the product; terms of the deal were not disclosed (6/29) KineMed Inc.* Sosei Co. Ltd. (Japan) KineMed will screen a number of Sosei molecules to determine their potential in new indications KineMed will use its in vivo KineMarker assays in the deal, terms of which were not disclosed (4/13) Large Scale Biology Corp. (LSBC) Bayer CropScience (unit of Bayer AG) Collaboration to investigate the plant-based expression of LSBC’s lysosomal acid lipase The goal is to develop a therapeutic product; terms of the deal were not disclosed (4/29) 208 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Lexicon Genetics Inc. (LEXG) NV Organon (the Netherlands; unit of Akzo Nobel) Collaboration under which Lexicon will create and analyze mouse knockouts of 300 genes to identify drug targets They will share R&D costs and any revenue; Lexicon gets $22.5M up front and research funding of up to $50M a year during the four-year target-function discovery portion of the alliance (5/17) Lorus Therapeutics Inc. (Canada; AMEX:LRP) Sumitomo Pharmaceuticals Co. Ltd. and Koken Co. Ltd. (both Japan) Deal to develop Lorus’ antisense cancer drug GTI-2601 with the partners’ collagen-based delivery system The companies will jointly own resulting compounds; terms of the deal were not disclosed (4/5) Macrocyclics Inc.* MDS Nordion (Canada) Deal to develop bifunctional chelates for use in molecular imaging and targeted therapeutics Terms of the three-year deal were not disclosed (5/26) Medarex Inc. (MEDX) Boehringer Ingelheim GmbH (Germany) BI will use Medarex’s UltiMAb technology to generate antibodies to disease targets Medarex gets technology access fees and could receive additional license fees and milestone payments, as well as royalties on resulting sales (6/14) Medarex Inc. (MEDX) Ono Pharmaceutical Co. Ltd. (Japan) Collaboration to research and develop a fully human anti-PD-1 antibody for treating cancer They will share costs through Phase II trials; then each would be responsible for its own territory; Medarex has rights in North America, Ono everywhere else (5/12) MerLion Sankyo Co. Pharmaceuticals Ltd. (Japan) Pte. Ltd.* (Singapore) Three-year collaboration under which MerLion will isolate new drug leads for Sankyo Sankyo would develop and commercialize resulting products; terms of the deal were not disclosed (4/20) Metabasis Therapeutics Inc. (MBRX) Merck & Co. Inc. Deal to develop and market small-molecule drugs to treat various diseases by activation of AMP-activated protein kinase Metabasis gets $5M up front and research funding; it also is entitled to milestone and royalty payments, along with a co-promotion option in the U.S.; total payments, excluding royalties, for the first product in the first indication could be $54M (6/27) Metabolex Inc.* Astellas Pharma Inc. (Japan) They extended for one year a 2002 deal to validate drug targets for the treatment of Type II diabetes and obesity Metabolex gets research funding and milestone payments under the extension; it would receive royalties on any sales and retained co-promotion rights in North and South America (5/2) Miikana Therapeutics Inc.* F. Hoffmann-La Roche Ltd. (Switzerland) Miikana got worldwide rights to Roche’s MKC-1, an anticancer agent in Phase II trials Roche gets an equity stake in Miikana, as well as undisclosed up-front, milestone and royalty payments (5/3) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 209 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Morphotek Inc.* GlaxoSmithKline plc (UK) Morphotek will apply its Morphodrome technology to GSK’s antibody producer lines to develop cell lines with improved characteristics Morphotek gets R&D funding for an initial project, which could lead to two more projects; Morphotek also could receive annual fees and is eligible for milestone payments (5/18) Myogen Inc. (MYOG) Novartis AG (Switzerland) They expanded a deal from 2003 to include Myogen’s histone deacetylase inhibitor program The expansion extends research funding for at least three years and includes undisclosed signing fees, as well as milestone and royalty provisions; Myogen also has certain co-promotion and profit-sharing options (5/26) Napo AsiaPharm Pharmaceuticals Group Ltd. Inc.* (Singapore) AsiaPharm got exclusive rights in China to develop and sell products derived from crofelemer for treating diarrhea Napo receives an equity investment and also would get royalty payments from sales of any products in China (6/15) Neose Technologies Inc. (NTEC) BioGeneriX AG (Germany; part of the Ratiopharm Group) License and option deal to use Neose’s GlycoPEGylation technology to develop a long-acting form of a marketed therapeutic protein The deal follows a previous supply and option agreement; Neose will get further up-front and research payments and could get up to $61.5M in milestone payments, as well as royalties on any sales (4/28) Neurologix Inc. (OTC BB: NRGX) Medtronic Inc. Deal to develop and market micro-infusion catheters to deliver gene therapy into the brain and central nervous system Neurologix got a $2M equity investment in the deal; Medtronic is entitled to milestone payments, and they would share revenues from any resulting device (5/2) Nuevolution A/S* (Denmark) Schering AG (Germany) Nuevolution will use its Chemetics technology to find new leads against targets provided by Schering Nuevolution will generate and screen libraries to identify the most potent and drug-like ligands; terms of the deal were not disclosed (6/21) Nuevolution A/S* (Denmark) Novo Nordisk A/S (Denmark) Collaboration to discover drug leads for targets provided by Novo Nuevolution will use its Chemetics technology in the effort; terms of the deal were not disclosed (4/12) Nuvelo Inc. (NUVO) Kirin Brewery Co. Ltd. (Japan) Collaboration to advance the preclinical growth factor NU206, which was developed under an existing alliance Nuvelo will lead development; it gets a $2M up-front payment and will pay 60% of the costs and get 60% of the revenues from the program (4/4) Odyssey Thera Inc.* Pfizer Inc. They expanded a deal to profile compounds across Odyssey’s panel of cell-based assays The project will focus on 500 compounds from multiple therapeutic areas; terms of the deal were not disclosed (5/17) 210 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Optimer Par Pharmaceuticals Pharmaceutical Inc.* Co. Inc. Collaboration on a narrowspectrum antibiotic (now named PAR-101) active against Clostridium difficile; it is in Phase II trials Par acquired a 16% partnership interest in Optimer; Optimer will fund development; Par would pay royalties on sales and has an option to develop three other Optimer compounds (5/3) OSI Merck & Co. Inc. Pharmaceuticals Inc. (OSIP) Merck got a nonexclusive license to a patent covering the use of dipeptidyl peptidase IV inhibitors with other antidiabetic agents OSI is entitled to up-front, milestone and royalty payments; the deal was made with the OSI diabetes and obesity unit Prosidion (6/30) Oxford BioMedica plc (UK; LSE:OXB) Pfizer Inc. Pfizer got rights to use the LentiVector gene delivery system for research activities Oxford BioMedica gets an up-front license payment and annual maintenance fees; further terms were not disclosed (6/6) Palatin Technologies Inc. (AMEX:PTN) Mallinckrodt Inc. They extended marketing deal covering Palatin’s infection imaging agent, NeutroSpec Mallinckrodt gained marketing rights in Europe; its rights now are worldwide; terms of the deal were not disclosed (6/15) Paradigm Therapeutics Ltd.* (UK) Ortho-McNeil Pharmaceuticals Inc. (unit of Johnson & Johnson) Ortho licensed rights to Paradigm programs with potential utility in pain and urinary incontinence Paradigm gets up-front research payments and is eligible to receive milestone and royalty payments (6/30) Paradigm Therapeutics Ltd.* (UK) Takeda Pharmaceutical Co. Ltd. (Japan) Three-year deal under which Paradigm will provide exclusive access to targets in certain central nervous system areas Paradigm gets up-front and exclusivity payments, and is entitled to milestones of up to $18M per product, as well as royalties on resulting sales (6/30) Perlegen Sciences Inc.* Mitsubishi Pharma Corp. (Japan) Perlegen got rights outside of Asia to the PPAR agonist, MCC-555, a product in the clinic for treating diabetes and other metabolic disorders Mitsubishi gets an up-front payment and could receive cash and equity milestone payments; it also gets rights to use predictive genetic markers identified by Perlegen; they each would pay royalties on sales (4/12) PharmaDesign Inc.* (Japan) Novartis AG (Switzerland) Novartis licensed a GPCR peptide ligand library designed by PDI Terms of the deal were not disclosed (4/20) Pharmasset Inc.* Bukwang Pharm. Co. Ltd. (South Korea) Pharmasset got certain rights to develop and sell Clevudine (L-FMAU) for treating chronic hepatitis B virus infections Pharmasset’s rights are in the Americas, Europe and Israel; Bukwang got an option to market the Phase II HBV product Racivir in Korea; terms were not disclosed (6/27) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 211 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pieris Proteolab AG* (Germany) Pharma Co. (Country) Term/Details (Date) Collaboration to develop an anticalin-based drug from Pieris for an undisclosed indication Pieris is responsible for research and for providing the active drug; Syngenta is responsible for development and commercialization; terms were not disclosed (4/13) Portola Astellas Pharma Pharmaceuticals Inc. (Japan) Inc.* Collaboration to advance the development of a series of Astellas preclinical compounds Portola scientists have identified the antithrombotic properties of the compounds; terms of the deal were not disclosed (6/6) Prosidion Ltd. (UK; unit of OSI Pharmaceuticals Inc.; OSIP) Undisclosed company The unnamed firm got nonexclusive rights to use DPIV inhibitors for Type II diabetes and related conditions The agreement covering dipeptidyl peptidase IV inhibitors includes undisclosed upfront, milestone and royalty payments to Prosidion (5/12) Proteologics Ltd.* (Israel) Teva Pharmaceuticals Industries Ltd. (Israel) Deal to study the feasibility of using drugs targeting ubiquitin ligases for cancer therapy Teva made an equity investment as part of the deal and has an option to license the program; if so, Proteologics would be entitled to milestone and royalty payments (5/3) Protez Sumitomo Pharmaceuticals Pharmaceuticals Inc.* Co. Ltd. (Japan) Deal to develop and commercialize SMP-601, Sumitomo’s injectable antibiotic, in North America and Europe Protez will provide development and commercialization milestones, as well as royalties on any sales; its license is exclusive in North America and Europe (5/17) Regenera Ltd. (Australia; ASX:RGA) Alcon Manufacturing Ltd. Alcon licensed a product used to assist in visualization of vitreous fluid during a vitrectomy Regenera gets an up-front payment and is entitled to milestone and royalty payments (double-digit in the U.S.) (4/7) Renovis Inc. (RNVS) Pfizer Inc. Worldwide deal to develop small molecules that target the vanilloid receptor, VR1, for treating pain, urinary incontinence and other conditions They will combine their current VR1 R&D programs; Renovis gets a $10M license fee and more than $7M in research funding over two years; Renovis also can earn $1 70M in milestone payments for each resulting product, as well as royalties on sales (5/31) Response Genetics Inc.* Roche Diagnostics (Switzerland) and Eli Lilly and Co. Deal to confirm biomarkers for use to identify patients most likely to respond to certain cancer therapies Roche and Lilly entered a collaboration initially focused on Lilly’s Alimta and Gemzar; they will work with Response Genetics on biomarker tests (5/1 1) Senetek plc (OTC BB:SNTKY) Signet Laboratories Inc. They finalized a deal under which Signet will manufacture and market monoclonal antibodies licensed to Senetek Signet will get a share of the revenues; the deal finalizes an amendment to an April 2004 deal (4/7) 212 Syngenta AG (Switzerland) Type/Product Area BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) 7TM Pharma A/S* (Denmark) Ortho-McNeil Pharmaceutical Inc. (unit of Johnson & Johnson) Collaboration to further develop 7TM’s program on oral compounds for treating asthma and allergic diseases 7TM gets an up-front fee, research funding and potential milestone payments, as well as royalties on resulting products; J&J takes over development responsibility (6/8) 7TM Pharma A/S* (Denmark) Procter & Gamble Pharmaceuticals Inc. Collaboration to research the use of therapeutic angiogenesis to identify candidates for treating vascular diseases P&G got exclusive rights to molecules derived from the program in exchange for an up-front fee, potential milestone payments and royalties on any sales; 7TM retained co-promotion rights in Scandinavia (4/12) Sinovac Biotech Ltd. (China; AMEX:SVA) LG Life Sciences Ltd. (South Korea) They agreed to collaborate on marketing efforts and vaccine supply for China and international markets They will work on international marketing of Sinovac’s Healive hepatitis A vaccine; Sinovac will introduce LG’s HepB vaccines into China, and they jointly will work on Sinovac’s influenza vaccine (Anflu); terms of the deal were not disclosed (5/18) SkyePharma plc (UK; SKYE) Mundipharma International Holdings Ltd. (UK) Deal under which Mundipharma will market and distribute DepoBupivacaine in Europe and elsewhere excluding the U.S., Canada and Japan SkyePharma gets $10M up front and up to $20M toward Phase III trials; it also is entitled to development and sales milestones that could bring total payments to $80M; SkyePharma would get 30% to 35% of sales, out of which it would pay for manufacturing (4/19) Sternberger Monoclonals Inc.* Covance Inc. Covance acquired the complete line of antibodies developed by Sternberger The deal was made by subsidiary Covance Research Products Inc.; terms of the deal were not disclosed (6/27) Sunesis Bristol-Myers Pharmaceuticals Squibb Co. Inc.* Sunesis licensed all rights to the cancer drug BMS-387032 (now SNS-032), a cyclindependent kinase inhibitor, and any related compounds BMS gets an up-front equity stake of $8M in Sunesis, and up to $29M in cash and equity milestone payments for the first approval; other milestones could total $49M million; BMS also would get royalties on sales (4/28) Symbollon Bioaccelerate Pharmaceuticals Holdings Inc. Inc. (OTC BB: SYMBA) Worldwide license and comarketing deal for IoGen, a Symbollon product for treating cyclic mastalgia Bioaccelerate will fund ongoing Phase III development, and would commercialize the product; they would share any resulting profits (4/13) Tranksaryotic Therapies Inc. (TKTX) Shire got rights to manufacture and distribute Dynepo outside of North America The license will take effect only if Shire’s planned $1.6B acquisition of TKT does not occur for specified reasons (4/21) Shire Pharmaceuticals Group plc (UK) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 213 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Valentis Inc. (VLTS) Schering AG (Germany) Expanded deal gives Schering nonexclusive rights to use GeneSwitch and PINC technologies in its research Valentis gets up-front license fee and is entitled to yearly maintenance fees; an earlier deal gave Schering rights to the technologies for use with two genes (6/7) Valentis Inc. (VLTS) Organon Laboratories Ltd. (UK) Organon licensed rights to use Valentis’ GeneSwitch gene-regulation technology for research purposes Valentis got a license fee and is entitled to yearly license maintenance fees; further terms of the nonexclusive license were not disclosed (5/25) Vectura Group plc (UK; LSE:VEC) and Arakis Ltd.* (UK) Novartis AG (Switzerland) Novartis gained rights to the two companies’ AD 237, as a monotherapy and with QAB149, for treating chronic obstructive pulmonary disease Arakis and Vectura each will get $15M up front; they each also are eligible to receive up to $172.5M in milestone payments, as well as royalties on any sales (4/13) Vical Inc. (VICL) Merck & Co. Inc. Merck exercised three options under an existing deal, giving it rights to use Vical’s nonviral gene delivery technology in cancer vaccine applications Vical gets a $3M payment and it entitled to milestone and royalty payments; Vical also has certain co-promotion rights for resulting products (6/8) Vitae GlaxoSmithKline Pharmaceuticals plc (UK) Inc.* Exclusive deal to develop renin inhibitors for treating hypertension and related cardiovascular disorders Vitae gets an up-front payment in cash and an equity investment, committed research funding and potential milestone and royalty payments; pre-commercial payments could total $175M for the lead product; Vitae also retains co-promotion rights in the U.S. (6/20) Xencor Inc.* Centocor Inc. (unit of Johnson & Johnson) Deal to use Xencor technology to create antibody candidates that Centocor will evaluate against an oncology target Xencor gets an up-front payment and is eligible to receive additional license fees, as well as milestone and royalty payments (7/18) Xencor Inc.* Eli Lilly and Co. Lilly exercised its option under a February 2004 deal to develop one or more proteins created by Xencor Xencor gets an up-front license fee and is eligible to receive milestone payments, as well as royalties on any sales (4/13) XenoTech LLC* Bristol-Myers Squibb Co. Three-year deal under which BMG got rights to immortalized Fa2N-4 hepatocytes for internal testing purposes Terms were not disclosed; XenoTech is licensee of the technology from MultiCell Technologies Inc. (5/23) Xenova Group plc (UK; XNVA) PharmaEngine Inc. (Taiwan) PharmaEngine licensed rights to the brain cancer product TransMID in China and South Korea Xenova gets an up-front payment, as well as potential milestone payments and royalties on any sales; it also will supply the product (4/13) 214 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) XOMA Ltd. (XOMA) Pharma Co. (Country) Merck & Co. Inc. Type/Product Area Term/Details (Date) Merck got rights to use bacterial cell expression technology for phage display in the discovery of antibody products XOMA gets an access fee along with potential milestone and royalty payments; Merck also got an option to use the technology in manufacturing antibodies, which would entail additional payments to XOMA (6/17) Xytis Fournier Pharmaceuticals Pharma (France) Ltd.* (UK) Xytis gained rights to develop and sell Fournier’s Anatibant for traumatic brain injury and possibly other indications Fournier Pharma retained manufacturing rights to the product, which contains its bradykinin B2 antagonist; further terms were not disclosed (6/13) YM BioSciences Inc. (Canada; TSE:YM) Deal to develop YM’s TheraCIMhR3 monoclonal antibody for certain patients with non-smallcell lung cancer Kuhnil will fund Korean development and provide an undisclosed amount of up-front, milestone and royalty payments; further terms were not disclosed (6/15) Kuhnil Pharmaceutical Co. (South Korea) THIRD QUARTER Adherex Technologies Inc. (AMEX:ADH) GlaxoSmithKline plc (UK) Adherex licensed GSK’s cancer product eniluracil, and GSK got an option to license Adherex’s ADH-1 (Exherin), a Phase II cancer compound GSK retains options to buy back eniluracil during development; if so, Adherex would be entitled to development and sales milestone payments of up to $120M, plus royalties; if GSK licenses ADH-1, Adherex would receive up-front, development and sales milestone payments of up to $100M, plus double-digit royalties on any sales (7/15) Aeres Biomedical Ltd.* (UK) Syngenta AG (Switzerland) Deal to develop one of Aeres’ humanized antibodies Terms of the deal were not disclosed; also, Syngenta made an undisclosed payment to Epimmune Inc., which assigned certain parts of its existing deal with Aeres to Syngenta (7/19) Affibody AB* (Sweden) Agilent Technologies Inc. Deal to develop advanced protein sample preparation solutions for biomarker discovery Affibody will design and develop engineered Affibody ligands for specific protein targets designated by Agilent; terms of the deal were not disclosed (8/23) Alfacell Corp. (ACEL) The Novartis Institute for Tropical Diseases (Singapore) NITD got rights to conduct in vitro testing to evaluate the activity of AC 03-636 in dengue fever In vivo studies in animal models potentially could follow; further details on the material transfer agreement were not disclosed (7/21) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 215 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Alnylam Novartis AG Pharmaceuticals (Switzerland) Inc. (ALNY) Multiyear collaboration to discover therapeutics based on RNA interference; Alnylam retains rights to its own pipeline and has certain profit-sharing options Novartis paid $58.5M up front for the purchase of 5.3M Alnylam shares at $1 1.1 1 each, representing 19.9% of the company; Alnylam will get another $10M up front and could receive a total of $700M if multiple products are developed, plus royalties on resulting sales (9/7) Alnylam Sigma-Aldrich Pharmaceuticals Corp. Inc. (ALNY) Sigma-Aldrich got nonexclusive rights to provide research products and services in RNA interference under Alnylam patents The Kreutzer-Limmer patent family covers short interfering RNAs and their use to mediate RNAi in mammalian cells; terms of the deal were not disclosed (7/19) Aphios Corp.* Bio Research Corp. and Tokyo Supply Ltd. (both of Japan) Deal to develop an oral, water-soluble paclitaxel prodrug for cancer Terms of the deal were not disclosed (7/19) Aptanomics SA* (France) Boehringer Ingelheim GmbH (Germany) Collaboration on aptamerbased target validation and drug discovery Aptanomics will provide aptamers and characterize their binding to therapeutic targets; terms of the deal were not disclosed (8/1) Astex Therapeutics Ltd.* (UK) Boehringer Ingelheim GmbH (Germany) Collaboration to discover, develop and market drug candidates against undisclosed disease targets Astex will provide candidates to BI; it gets up-front and research payments, along with potential milestone and royalty payments (8/31) Astex Therapeutics Ltd.* (UK) AstraZeneca plc (UK) Collaboration to discover and commercialize small-molecule inhibitors of protein kinase B for use as anticancer agents Astex gets $5M up front, research funding and up to $270M in regulatory and sales milestones; it would get double-digit sales royalties, and retains an option to co-promote resulting products in the U.S. (7/27) Avalon Novartis AG Pharmaceuticals (Switzerland) Inc.* Collaboration to discover smallmolecule compounds against a pathway selected by Novartis Avalon is entitled to an up-front payment, research support and milestone payments (9/13) Avanir AstraZeneca Pharmaceuticals plc (UK) Inc. (AMEX:AVN) Collaboration to discover and develop Reverse Cholesterol Transport-enhancing compounds for treating cardiovascular disease Avanir gets $10M up front and is eligible for up to $330M in milestone payments, as well as royalties rising from single-digit to low-double-digit rates; AstraZeneca is responsible for costs and development (7/1 1) BioFocus plc (UK; AIM:BIO) BioFocus will use its expertise in GPCR drug discovery to generate leads for Organon targets The deal followed a screening collaboration between the companies; terms were not disclosed (8/8) 216 NV Organon (the Netherlands) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Bio-Medisinsk Innovasjon A/S* (Norway) Pharma Co. (Country) GlaxoSmithKline plc (UK) Type/Product Area Term/Details (Date) Collaboration covering the 5-HT4 receptor antagonist piboserod (SB 207266) BMI will complete Phase II testing; GSK then has an option to take over development and marketing in heart failure in exchange for a license fee, milestone payments and royalties on any sales (9/19) BioSante Unnamed Pharmaceuticals European Inc. (AMEX:BPA) company Option deal to use BioSante’s calcium phosphate nanotechnology in the development of a series of allergy products BioSante gets $0.25M up front; if a license agreement results, it would get license fees, annual maintenance payments and potential milestone and royalty payments (9/14) BioSyntech Inc. (Canada; TSE:BSY) Nicholas Piramal India Ltd. (India) NPIL acquired exclusive rights to BioSyntech products in India, Pakistan, Sri Lanka, Bangladesh, Laos, Cambodia, Vietnam and the Philippines NPIL is purchasing 7.5M BioSyntech shares at C$0.80 each ($4.95M in stock) and will own about 17% of the company; they also will explore collaborative opportunities (7/8) BioVeris Corp. (BIOV) Baxter Healthcare Corp. BioVeris licensed rights to a portfolio of vaccine candidates covering multiple diseases The vaccines are based on a conjugate technology platform; Baxter is entitled to up-front, milestone and royalty payments (8/1 1) BioVisioN AG* (Germany) Abbott Laboratories Collaboration on research to discover novel biomarkers for lung cancer BioVisioN will analyze biological samples provided by Abbott; it will get research payments and could get milestone and royalty payments (9/9) Caliper Life Sciences Inc. (CALP) Agilent Technologies Inc. Agilent got nonexclusive rights to use microfluidics technology for development of clinical diagnostic applications Agilent will develop the applications on its platforms; also, Caliper will exclusively supply planar LabChip products to Agilent for five years (7/12) Caprion Boehringer Pharmaceuticals Ingelheim GmbH Inc.* (Canada) (Germany) Deal to to identify biomarkers of metabolic and inflammatory disease using Caprion’s CellCarta proteomics platform Caprion will identify pharmacodynamic markers in plasma following administration of preclinical compounds; terms were not disclosed (7/12) Celera Diagnostics (NYSE:CRA) Merck & Co. Inc. They extended their deal to develop treatments for Alzheimer’s disease Celera will genotype gene-based mutations in sample collections as part of an effort to discover targets and biomarkers; terms were not disclosed (9/7) Cell Signaling Technology Inc.* Johnson & Johnson Pharmaceutical Research & Development Deal to use CST’s PhosphoScan technology to identify phosphorylation sites and biomarker kinase targets Terms of the deal were not disclosed (7/1 1) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 217 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Cellzome Inc.* Novartis Pharma AG (Switzerland) They expanded a deal under which Cellzome is mapping the protein networks of several signaling pathways The additional work will focus on providing more in-depth functional analyses of target candidates and signaling aspects of disease pathways; terms were not disclosed (7/26) CeMines Inc.* Colorado Heart & Body Imaging LLC CHBI got rights to use technology from CeMines in upcoming clinical studies CeMines’ CellCorrect LAb Detection Test Kits will be used in a program to detect lung cancer (9/13) Cerenis Therapeutics* Nippon Chemiphar Co. Ltd. (Japan) Deal to develop small-molecule therapies based on PPAR (peroxisome proliferator activated receptor) delta agonists Cerenis gets access to PPAR delta agonists for developing HDL therapies to help reduce cholesterol buildup; Nippon gets up to $30M in milestone payments and royalties on any sales; it also gets rights in Asia; Cerenis has rights elsewhere (8/30) ChemDiv Inc.* Schering AG (Germany) ChemDiv will use its smallmolecule chemistry expertise to support Schering programs The medicinal chemistry research deal will run at least two years; terms were not disclosed (9/14) Chronogen Inc.* (Canada) Inpharzam Ricerche (Swiss unit of Zambon Group SpA) Deal to identify small molecules for treating cardiovascular and metabolic diseases induced by oxidative damage and/or lipid disorders Chronogen will screen the Inpharzam library in the deal; further details were not disclosed (7/1) Ciphergen Biosystems Inc. (CIPH) Quest Diagnostics Inc. Deal to develop and sell proteomic diagnostic tests based on Ciphergen’s SELDI ProteinChip technology Quest purchased 17% of Ciphergen, or 6.2M shares, for $15M; it got a five-year warrant to purchase another 2.2M shares at $3.50 each; Quest also provided a loan of up to $10M that would be forgiven if certain milestones are met (7/22) Collegium Pharmaceutical Inc.* BTG plc (UK) Collaboration to develop CP-141, a new formulation of a product used to treat asthma They will co-fund the development program and share any resulting revenues (8/31) CombinatoRx Inc.* HenKan Pharmaceutical Co. (Taiwan) HenKan got rights to develop and sell the cancer agent CRx-026 in Taiwan, China and South Korea CombinatoRx gets $500,000 up front and up to $23M in development and commercial milestone payments, plus royalties on sales; HenKan also will fund certain Phase II trials (7/18) Competitive Technologies Inc. (AMEX:CTT) Beckman Coulter Inc. Beckman Coulter got a license to a homocysteine assay Competitive Technologies gets a license fee and royalties on sales of homocysteine assay products (7/28) 218 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Curis Inc. (CRIS) Procter & Gamble Pharmaceuticals Deal to evaluate and develop treatments for hair growth regulation using Curis’ Hedgehog agonist technology Curis gets $0.5M up front and up to $2.8M in preclinical milestones, as well as royalties on any sales; milestone payments could exceed $100M if a product is marketed; Curis retains certain co-development options and rights in certain fields (9/19) Cytomyx Holdings plc (UK; AIM:CYX) Wyeth Pharmaceuticals Cytomyx got rights to create and market cell lines expressing the ion channel Kv4.3 and four KChIP accessory subunits Cytomyx will use the technology in research reagents for use in drug discovery and screening; terms were not disclosed (8/4) Depomed Inc. (DEPO) Esprit Pharma Inc. Esprit got exclusive rights to market Proquin XR in the U.S and Puerto Rico; the product was approved for treating uncomplicated urinary tract infections Depomed gets $30M up front and $20M more within 24 months, as well as royalties of 15% to 25%; launch of the extendedrelease formulation of ciprofloxacin is expected in 4Q:05 (7/28) Dyax Corp. (DYAX) Merck KGaA (Germany) Merck got nonexclusive rights to phage display libraries for discovery and development of antibody and peptide drugs Dyax gets an up-front license fee, as well as annual maintenance fees and potential milestone and royalty payments; Merck also has an option under which Dyax would perform funded research (8/18) Epitome Biosystems* EMD Biosciences (unit of Merck KGaA; Germany) Deal under which Epitome will develop reagents to measure intracellular signaling proteins Epitome will get a technology access fee and could receive development payments and royalties on product sales (9/14) Evotec AG (Germany; FSE: EVT) Procter & Gamble Pharmaceuticals Inc. Evotec will provide pharmaceutical discovery and chemical development services to P&G The deal follows a 2004 program between them in which Evotec screened for a P&G target; terms were not disclosed (7/25) Evotec AG (Germany; FSE: EVT) Almirall Prodesfarma SA (Spain) Evotec will design and synthesize for Almirall drug-like compounds across a range of chemical templates Terms of the two-year library synthesis agreement were not disclosed (7/21) Galapagos NV (Belgium; Euronext:GLPG) Novartis Pharmaceuticals UK Ltd. Galapagos’ Galadeno unit will design a research program for Novartis for functional assays in human primary cell assays Galadeno will get research payments in exchange for providing technology, reagents and support to Novartis (7/6) Genaissance will apply its HAP Technology in order to identify genetic markers related to drug response The companies will co-own technology coming from the pharmacogenomic effort, and both would be entitled to royalties on resulting diagnostic products (9/21) Genaissance Otsuka Pharmaceuticals Pharmaceutical Inc. (GNSC) Co. Ltd. (Japan) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 219 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Genaissance NV Organon Pharmaceuticals (the Netherlands) Inc. (GNSC) Deal to apply Genaissance’s HAP technology for pharmacogenetic research in clinical trials They will look at modulation of the HPA stress axis for treating psychiatric disorders; Genaissance gets license fees and research funding and has certain rights to develop companion genetic tests (7/18) Genedata AG* (Switzerland) DSM Biologics (the Netherlands) DSM Nutritional Products licensed rights to biologic solutions from Genedata DSM got rights to the Genedata Phylosopher and Genedata Expressionist technology under undisclosed terms (7/28) Gene Logic Inc. (GLGC) Pfizer Inc. Gene Logic will seek new therapeutic indications for a number of Pfizer drug candidates not currently in active development Gene Logic is entitled to milestone payments on each compound and royalties on sales of any resulting drugs (9/27) Gen-Probe Inc. (GPRO) Millipore Corp. Deal to exclusively develop and sell nucleic acid testing products for microbiological and virus monitoring Gen-Probe primarily will be responsible for assay development and manufacturing, while Millipore will manage commercialization (8/31) Geron Corp. (GERN) Merck & Co. Inc. Collaboration and license agreement to develop a cancer vaccine targeting telomerase; Merck also acquired an option to negotiate a deal for Geron’s dendritic cell-based telomerase vaccine that’s in Phase I/II trials Geron gets an up-front payment and is eligible to receive milestone and royalty payments; Merck also will invest in Geron’s next round of financing; Geron got an option payment in the second deal; terms would be negotiated upon exercise of the option (7/18) Halozyme Therapeutics Inc. (AMEX:HTI) Baxter Healthcare Corp. Baxter exercised its option to market Hylenex in the European Union Baxter already had rights in the U.S. to Hylenex, a recombinant human hyaluronidase being developed for use as a spreading agent; terms were not disclosed (8/8) Human Genome Sciences Inc. (HGSI) GlaxoSmithKline plc (UK) GSK exercised its option to jointly develop and sell HGS-ETR1 (mapatumumab), a drug candidate for cancer GSK exercised an option from a 1 996 deal on the Phase II product; they will equally share costs going forward and any profits (8/18) Human Genome Sciences Inc. (HGSI) GlaxoSmithKline plc (UK) GSK exercised its option to jointly develop and sell LymphoStat-B for rheumatoid arthritis and lupus The option from the 1996 deal was exercised following Phase II trials; they will equally share costs going forward and any profits (7/7) Illumina Inc. (ILMN) GlaxoSmithKline plc (UK) Illumina will conduct genetic studies for thousands of GSK samples covering multiple projects Terms of the multiyear genotyping services agreement were not disclosed (9/22) 220 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) ImClone Systems Inc. (IMCL) UCB Group (Belgium) Deal to develop and market UCB’s CDP-791, an antibody targeting VEGFR-2; the cancer drug is entering Phase II trials They will share development costs and worldwide profits; ImClone has commercialization rights in North America, with UCB having such rights in the rest of the world (8/15) Immunetrics Inc.* Eli Lilly and Co. Deal to apply in silico modeling technology to clinical trial design Immunetrics will apply the technology to an undisclosed project at Lilly; terms were not disclosed (9/7) ImmunoGen Inc. (IMGN) Sanofi-Aventis Group (France) Sanofi exercised its right to extend their collaboration focused on antibody-based anticancer products ImmunoGen will get $18.2M in research support over the 12 months beginning Sept. 1, 2006; ImmunoGen remains entitled to milestone and royalty payments from the 2003 deal (8/31) Indevus Schering AG Pharmaceuticals (Germany) Inc. (IDEV) Indevus licensed U.S. rights to market Nebido, a longacting injectable testosterone preparation; it is approved in Europe Indevus will pay $7.5M up front and $5M upon U.S. approval, and up to $17.5M in regulatory and commercial milestones; Schering also would get a percentage of net sales (7/29) InforSense Ltd.* (UK) Bayer Healthcare AG (Germany) Bayer will use InforSense technology to enhance its drug discovery informatics infrastructure Terms of the deal were not disclosed (9/8) Innocoll Inc.* Medexis SA (Greece; part of the Gerolymatos Group of Companies) Deal to develop a woundhealing product based on Innocoll’s CollaRx membrane technology Medexis will fund development and be responsible for regulatory applications; terms of the deal were not disclosed (9/8) Inpharmatica Ltd.* (UK) Tibotec Pharmaceuticals Ltd. (Belgium; unit of Johnson & Johnson) Tibotec will use Inpharmatica’s Chematica technologies to study the action of antiviral compounds from Tibotec The technology links compounds with putative molecular targets; terms of the deal were not disclosed (8/1) Intercell AG (Austria; VSE:ICLL) Sanofi-Pasteur Group (France) Sanofi exercised its option on exclusive rights to certain bacterial vaccine antigens Intercell gets license, research and success fees of €3M; it is entitled to further milestone payments of up to €20M, as well as royalties on resulting sales (7/1) Collaborations focused on identifying biomarkers that may drive the response to anticancer drugs Ipsogen will collect samples from clinical trials and will perform sample processing and pathology analysis, while Genaissance will perform genotyping and data analysis for the undisclosed partners (9/12) Ipsogen SAS* Two (France) and pharmaceutical Genaissance companies Pharmaceuticals Inc. (GNSC) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 221 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Isis Eli Lilly and Co. Pharmaceuticals Inc. (ISIS) They extended a four-year antisense drug discovery collaboration an additional two years Lilly also got rights to another Isis drug, an inhibitor of STAT-3 for cancer; Isis is entitled to milestones and royalties from that product; as part of the extension, Isis converted a $100M loan from Lilly into 2.5M shares of Isis common stock (8/8) Isotechnika Inc. (Canada; TSE:ISA) Atrium Medical Corp. Exclusive deal to develop Isotechnika’s TAFA93 and ISA247 with drug-eluting devices in various indications Isotechnika gets $3M up front and is entitled to milestone and royalty payments on resulting products; Atrium will fund development (9/30) Ixion Biotechnology Inc.* Q-Med AB (Sweden) Ixion transferred the assets and employees related to its oxalate technology to Q-Med Ixion received almost all of Q-Med’s Ixion stock, $344,000 in cash and $6M in debt forgiveness from its former majority shareholder; Ixion regained its independent status (7/1 1) KeyNeurotek AG* (Germany) Schwarz Pharma AG (Germany) Schwarz will use Telomics technology from KeyNeurotek to characterize drug candidates in its urology program Terms of the deal were not disclosed (7/14) Labopharm Inc. (Canada; TSE:DDS) Purdue Pharma LP Purdue got exclusive rights to market Labopharm’s oncedaily formulation of the analgesic tramadol in the U.S. Labopharm gets $20M up front, up to $40M upon FDA approval and additional payments if sales targets are reached; it also would get royalties of 20% to 25% (8/15) Lipoxen Technologies Ltd.* (UK) Baxter Healthcare Corp. Lipoxen will apply its technology to develop blood-clotting factors with extended biological activity Lipoxen gets research funding along with potential milestone and royalty payments (9/27) Lipoxen Technologies Ltd.* (UK) National Biotechnologies OAO (Russia) National Biotechnologies got certain rights to extended-release insulin and interferon products Lipoxen gets $750,000 up front and is entitled to royalty payments; the license covers Russia, Ukraine and Kazakhstan (9/27) They amended a 2004 deal under which MAP is applying Elan’s NanoCrystal technology to certain inhalation therapies MAP gets additional rights to use the technology for treating multiple respiratory diseases, including asthma; it covers nebulized delivery of budesonide and combinations of budesonide with beta agonists; terms were not disclosed (7/27) MAP Elan Corp. plc Pharmaceuticals (Ireland) Inc.* 222 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) MedImmune Inc. (MEDI) Pharma Co. (Country) GlaxoSmithKline plc (UK) Type/Product Area Term/Details (Date) MedImmune got rights to certain anti-staphylococcal monoclonal antibodies, including the Phase II product BSYX-A1 10 GSK gets an up-front payment as well as potential milestone payments and royalties on sales; MedImmune also assumed responsibility for any milestone and royalty payment obligations to Biosynexus (8/29) MerLion Merck & Co. Inc. Pharmaceuticals Pte. Ltd.* (Singapore) They are expanding and extending deal to discover and develop drugs derived from natural products chemistry The deal was extended two years and expanded to include additional targets; MerLion is entitled to up-front, milestone and royalty payments (7/26) Mesoblast Ltd. (Australia; ASX: MSB) Unnamed medical device company The device company will provide carrier materials to Mesoblast The materials will be used in combination with Mesoblast’s adult stem cells in preclinical trials (8/24) Migenix Inc. (Canada; TSE:MGI) Schering-Plough Corp. Schering-Plough got first rights to negotiate a license to celgosivir (MX-3253), a Phase II product for hepatitis C Schering-Plough will supply Pegetron and certain services for Migenix’s upcoming Phase II combination study; it will have a limited period to review the data and negotiate a license (7/13) Millennium Schering-Plough Pharmaceuticals Corp. Inc. (MLNM) Schering-Plough acquired all rights in the U.S. to the GP IIb/IIIa inhibitor Integrilin; they had been co-promoting the drug in the U.S. Millennium gets $35.5M up front and royalties on sales; the minimum royalties in 2006 and 2007 are $85M each year; SP also will pay $45M to $50M to Millennium for existing Integrilin inventories (7/22) MorphoSys AG (Germany; FSE:MOR) Centocor Inc. (unit of Johnson & Johnson) MorphoSys will generate antibodies to a target molecule discovered in their collaboration MorphoSys is entitled to licensing fees and milestone and royalty payments (9/6) MorphoSys AG (Germany; FSE:MOR) Eli Lilly and Co. Cross-licensing deal covering the use of certain recombinant protein technologies MorphoSys is entitled to licensing fees and milestone and royalty payments on covered products developed by Lilly; the deal settled patent litigation (9/23) MorphoSys AG (Germany; FSE:MOR) Shionogi & Co. Ltd. (Japan) Shionogi licensed access to the HuCAL GOLD antibody library for use in drug discovery programs MorphoSys gets an up-front payment and annual user fees under terms of the threeyear deal (9/7) Nektar Therapeutics (NKTR) Baxter Healthcare Corp. Deal to develop PEGylated forms of blood-clotting proteins for treating hemophilia Nektar is entitled to research payments along with potential milestone payments, manufacturing revenues and sales royalties (9/29) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 223 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) NexMed Inc. (NEXM) Novartis International Pharmaceutical Ltd. Novartis got worldwide rights to NexMed’s Phase I product NM100060, a lacquer treatment for nail fungus NexMed gets $4M up front and up to $47M in milestone payments, as well as royalties on any resulting sales (9/15) NicOx SA (France; Eurolist: NICOX) Grupo Ferrer Internacional SA (Spain) They expanded deal to discover and develop nitric oxidedonating corticosteroids for dermatology applications Ferrer got an option to acquire U.S. rights; NicOx is eligible to receive more milestone and royalty payments than called for in the original deal (9/15) Nobex Corp.* Biocon Ltd. (India) Agreement to co-develop an oral brain-type natriuretic peptide product for treating cardiovascular disease They will use the oral peptide delivery technology of Nobex with the peptide production capabilities of Biocon; terms of the deal were not disclosed (8/23) Paion AG (Germany; FSE:PA8) H. Lundbeck A/S (Denmark) Deal to develop and market Paion’s Phase III product Desmoteplase for stroke everywhere except the U.S. and Canada Paion gets €15M up front and up to €50M in milestones for the the indication of stroke; Paion has co-promotion options and would get double-digit royalties on sales where Lundbeck has exclusivity (7/1 1) ParAllele BioScience Inc.* Merck & Co. Inc. Deal to discover genetic variations applicable to cancer susceptibility, prognosis or response to therapy ParAllele will use its genotyping technology to characterize genetic changes in tumor samples identified by Merck; terms of the deal were not disclosed (7/6) Perlegen Sciences Inc.* GlaxoSmithKline plc (UK) New deal enables multiple genetics-related studies to be conducted over a period of time It is the third deal between the companies; terms were not disclosed (8/31) Pharmacopeia Drug Discovery Inc. (PCOP) NV Organon (the Netherlands) They extended drug-discovery collaboration from 2002 until 2007 Organon elected to continue the deal by accepting the latest preclinical lead candidate generated by Pharmacopeia; specific terms were not disclosed (8/30) Pharmacopeia Drug Discovery Inc. (PCOP) Allergan Inc. Allergan got rights to angiogenesis-targeting compounds in the field of ophthalmology Pharmacopeia gets an up-front payment and may get preclinical and clinical payments, plus milestone and royalty payments (7/12) Primagen Holding BV* (the Netherlands) Focus Diagnostics Inc. Focus got rights to develop PCR detection for human coronavirus NL63 Terms of the license deal were not disclosed (9/12) Novacea Inc.* Pierre Fabre Medicament SA (France) Novacea acquired U.S. and Canadian rights to the oral chemotherapeutic agent vinorelbine The drug is approved in Europe; Pierre Fabre is entitled to up-front, milestone, manufacturing and royalty payments (7/25) 224 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Odyssey Thera Inc.* Bristol-Myers Squibb Co. Odyssey will profile certain BMS compounds in its cellbased assays The goal is to further characterize mechanism of action and pathway activity; terms of the deal were not disclosed (7/14) OriGene Technologies Inc.* Eisai London Research Laboratories Eisai licensed OriGene’s FlagArray platform for highthroughput target discovery Terms of the deal were not disclosed (8/2) OSI Unnamed Pharmaceuticals Japanese Inc. (OSIP) company The pharmaceutical firm got a nonexclusive license to use dipeptidyl peptidase IV inhibitors for treating Type II diabetes and related conditions OSI is entitled to up-front, milestone and royalty payments; the deal was made with the OSI diabetes and obesity unit Prosidion (7/7) Revivicor Inc.* Zimmer Holdings Inc. Zimmer acquired worldwide rights to genetically engineered xenogeneic tissues for regenerative therapies Zimmer initially plans to develop the technologies for orthopedic applications; terms of the deal were not disclosed (9/20) Sangamo BioSciences Inc. (SGMO) LifeScan Inc. (unit of Johnson & Johnson) They expanded deal to use Sangamo’s zinc finger DNAbinding proteins to develop therapeutic cell lines for treating diabetes Sangamo will receive expanded research funding from LifeScan through 2006 under the second expansion of the deal (9/14) Sangamo BioSciences Inc. (SGMO) Novo Nordisk A/S (Denmark) Novo got access to Sangamo’s zinc finger DNA-binding protein technology Novo will evaluate the technology for use in enhancing protein production; terms of the deal were not disclosed (9/7) Santhera Takeda Pharmaceuticals Pharmaceutical AG* (Switzerland) Co. Ltd. (Japan) Collaboration to develop and market Idebenone (SNT-MC17), a small-molecule drug for treating Friedreich’s ataxia Santhera gets €5M up front and potential milestone and royalty payments; Takeda gets exclusive rights in Europe; Phase III trials are planned (8/3) Sareum Holdings plc (UK; AIM:SAR) Almirall Prodesfarma SA (Spain) Sareum will provide protein structure determination services to accelerate drug discovery research at Almirall The goal is to determine how Almirall’s drug candidates interact with their target proteins; terms were not disclosed (8/10) SeBo GmbH* (Germany) Novartis AG (Switzerland) Novartis acquired global rights to an oral phosphate binder for treating elevated serum phosphate levels Rights to the Phase I compound include patients with chronic kidney disease or patients already on dialysis; terms of the deal were not disclosed (8/18) Sirna Therapeutics Inc. (RNAI) Allergan Inc. Deal to develop Sirna-027, a Phase I product for age-related macular degeneration, and other RNAi-based drugs for ophthalmic diseases Sirna gets $5M up front and is eligible for development milestones of up to $245M in addition to research funding and royalties on any resulting sales; Sirna also can get manufacturing revenues (9/29) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 225 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Strand Life Sciences Pvt. Ltd.* (India) Elan Corp. plc (Ireland) Strand will use its in silico technologies to support Elan drug discovery efforts Terms of the deal were not disclosed (9/29) Structural GenomiX Inc.* Eli Lilly and Co. They extended for three years an April 2003 deal focused on Lilly’s drug discovery programs SGX is applying its technologies to Lilly drug targets to determine crystal structures and data on target/inhibitor complexes; terms were not disclosed (7/13) TNO Pharma* (the Netherlands) Mitsubishi Pharma Corp. (Japan) Collaboration to further characterize a set of disease targets from Mitsubishi TNO will use its siRNA-based knockdown technology and disease models in the deal, terms of which were not disclosed (9/6) Tripos Inc. (TRPS) Servier (France) Collaboration to further design and synthesize compounds for potential drug development Tripos will apply its chemistry technologies in the deal, terms of which were not disclosed (8/30) Velcura Therapeutics Inc.* Nippon Chemiphar Co. Ltd. (Japan) Deal to further develop small-molecule therapies for osteoporosis and other bone diseases A lead compound has been discovered; the deal pairs Chemiphar’s expertise in drug discovery with Velcura’s process of growing human bone in tissue culture (8/9) Vical Inc. (VICL) Merck & Co. Inc. Merck got options to use Vical’s nonviral gene delivery technology for additional cancer targets In exchange, Vical got nonexclusive rights to use the technology for vaccines against HIV; also, Merck got an option to use electroporation-enhanced delivery technology with HIV vaccines (9/12) ViroLogic Inc. (VLGC) Schering-Plough Corp. ViroLogic will use its HIV resistance testing technology to support discovery and development at SP ViroLogic will get $4.8M under the multiyear service agreement; the focus is on Schering-Plough’s CCR5 receptor antagonist, vicriviroc (7/6) XOMA Ltd. (XOMA) Wyeth Wyeth got a nonexclusive license to XOMA’s expression technology Wyeth will use the technology to develop and produce recombinant proteins; terms of the deal were not disclosed (9/7) Affectis NV Organon Pharmaceuticals (the Netherlands) AG* (Germany) Affectis will apply its technologies to the validation of gene targets in depression and anxiety Terms of the deal were not disclosed (1 1/2) Affibody AB* (Sweden) Affibody will develop a product for the removal of a target molecule from fluid mixtures Asahi Kasei intends to develop a medical device using the Affibody molecule; terms of the deal were not disclosed (1 1/1) FOURTH QUARTER 226 Asahi Kasei Corp. (Japan) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Affymetrix Inc. (AFFX) Applied Biosystems Group ABG got nonexclusive rights to patents related to the use and sale of microarrays for gene expression analysis The license will be applied to the expansion of the Applied Biosystems Expression Array System; terms were not disclosed (12/22) Affymetrix Inc. (AFFX) GlaxoSmithKline plc (UK) GSK got rights to use the Affymetrix GeneChip Human Mapping 500K Array Set to find genetic variations GSK will use the arrays to perform wholegenome association studies across tens of thousands of samples; terms of the deal were not disclosed (10/4) Agensys Inc.* Merck & Co. Inc. Deal to develop and sell Agensys’ AGS-PSCA, a fully human monoclonal antibody to prostate stem cell antigen; Merck also got rights to the PSCA target and to any resulting products Agensys gets $17.5M up front and up to $1 1.5M more over 12 months; successful development of AGS-PSCA would trigger milestone payments of $95M and more than $170M if multiple oncology indications are developed; Agensys also would get royalties on sales (10/17) Agensys Inc.* Sanofi-Aventis Group (France) Collaboration with Sanofi Pasteur to develop vaccines against colorectal and prostate cancers Sanofi gets an option to license up to six targets for development in the three-year deal; Agensys gets an up-front payment, research funding and progress payments; it also could receive license fees, milestone payments and royalties on resulting sales (10/10) Albany Molecular Research Inc. (AMRI) Bristol-Myers Squibb Co. BMS got rights to compounds that encompass biogenic amine reuptake inhibitors for treating depression and other CNS disorders AMRI gets an up-front payment of $8M and $10M in research funding over three years; it also is eligible to receive up to $66M per compound in development and regulatory milestone payments for the first two compounds and milestone payments of up to $22M for subsequent compounds, as well as royalties on resulting sales (10/24) Alder BioSchering-Plough pharmaceuticals Corp. Inc.* Deal to use Alder technologies to identify and produce antibodies more rapidly and cost effectively Alder will work with up to 10 Schering-Plough products; Alder is eligible to receive milestone payments, research support and royalties on each of the antibodies (12/2) Alimentary Health Ltd.* (Ireland) Procter & Gamble Co. They entered a worldwide license agreement covering gastrointestinal indications Details on the deal were not disclosed; they are partners in the Alimentary Pharmabiotic Centre at University College Cork (12/14) Alligator Bioscience AB* (Sweden) Undisclosed European company Deal to optimize an undisclosed protein using Alligator’s FIND technology Alligator is entitled to milestone payments in the deal (10/17) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 227 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Ambit Biosciences Corp.* Bristol-Myers Squibb Co. BMS gets access to kinase profiling technology for use in discovery and development, under a five-year expansion of an existing deal Ambit gets an up-front payment, an equity investment and profiling revenues over the five-year term; it also got rights to develop candidates from a cancer-directed preclinical kinase inhibitor program (12/12) Ambrx Inc.* F. Hoffmann-La Roche Ltd. (Switzerland) Deal to use Ambrx technology to develop next-generation proteins and peptides The initial focus is on pegylated interferonalpha molecules; Ambrx is entitled to license fees, research funding, milestone payments and royalties on sales (12/8) American Pharmaceutical Partners Inc. (APPX) Taiho Pharmaceutical Co. Ltd. (Japan) Taiho got rights in Japan to Abraxane, a taxane product for solid tumors APPI is entitled to up-front and milestone payments in excess of $50M, as well as royalties on sales; it also will supply product for the Japanese market (1 1/15) Apoxis SA* (Switzerland) Astellas Pharma GmbH (Germany) Apoxis acquired worldwide rights to FK866, a cancer compound it renamed APO866 Phase II trials are planned; Astellas gets an up-front payment and potential milestone and royalty payments (12/15) Ardana plc (UK; LSE:ARA) Pharmacuro ApS (Denmark) Pharmacuro got rights to market Striant SR in the Nordic region Pharmacuro anticipates launching the testosterone replacement therapy in 2006; terms of the deal were not disclosed (1 1/9) Array BioPharma Inc. (ARRY) Ono Pharmaceutical Co. Ltd. (Japan) Collaboration to create smallmolecule drug candidates against a series of kinases selected by Ono Ono will provide funding to access Array’s Drug Discovery Platform; Array also is entitled to milestone payments and royalties on any resulting sales (1 1/4) Astex Therapeutics Ltd.* (UK) Novartis AG (Switzerland) Novartis got rights to Astex’s cell-cycle inhibitor AT931 1, and an option to license the cell-cycle inhibitor AT7519 Astex gets up-front and deferred equity payments totaling $25M and is entitled to research funding, reimbursement fees, option payments and milestones; total funding, excluding royalties, could reach $520M if three products are successfully developed (12/6) AtheroGenics Inc. (AGIX) AstraZeneca plc (UK) AstraZeneca got worldwide rights to AGI-1067, an AtheroGenics product in Phase III trials for treating atherosclerosis AtheroGenics gets $50M up front and up to $300M in regulatory and development milestones; it also is entitled to up to $650M in sales-related milestones, as well as royalties on sales (12/22) Deal to use AVEO’s platform to identify likely responders to cancer drugs being developed by Merck AVEO gets an equity investment, annual research funding and potential milestone payments; the deal involves use of AVEO’s Human Response Prediction platform (1 1/2) AVEO Merck & Co. Inc. Pharmaceuticals Inc.* 228 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Benitec Ltd. (Australia; ASX:BLT) Pharma Co. (Country) Sigma-Aldrich Corp. Type/Product Area Term/Details (Date) Sigma-Aldrich got an exclusive license to use Benitec’s RNAi technology in the research reagent market Benitec received a $2M license payment and a $2.5M equity investment at A$0.17 per share; it also is entitled to revenue from royalties and sublicenses (10/24) BioCryst Hoffmann-La Pharmaceuticals Roche Inc. Inc. (BCRX) Roche got exclusive rights to the Phase I compound BCX4208, which is being developed for transplantation and autoimmune indications BioCryst gets $25M up front and $5M for material; milestone payments could reach $530M; BioCryst would get royalties on any sales; BioCryst retains certain U.S. co-promotion rights (1 1/30) BioSyntech Inc. (Canada; CDNX:BSY) Kuhnil Pharma Co. Ltd. (South Korea) Kuhnil got exclusive rights in Korea to BioSyntech’s BSTCarGel and BST-InPod products Kuhnil purchased 1.5M shares for $1.2M; further details on the letter of intent were not disclosed (10/18) BioTrove Inc.* Schering-Plough Research Institute BioTrove will use its RapidFire Lead Discovery service on Schering-Plough targets BioTrove will provide assay development and high-throughput screening under the expansion of an existing agreement (12/6) Cambridge Antibody Technology Group plc (UK; CATG) Genencor International Inc. (unit of Danisco A/S; Denmark) CAT acquired the Phase II cancer drug GCR-3888 and the preclinical cancer drug GCR-8015; it also hired 10 people involved in the program Genencor is getting $14M in the form of 1.17M CAT shares, or 2.3% of CAT; it could get another $2M in milestone payments (1 1/1) Caprion AstraZeneca plc Pharmaceuticals (UK) Inc.* (Canada) Deal under which AstraZeneca will evaluate a number of prostate cancer drug targets discovered by Caprion Caprion gets an up-front payment and license fees, and could get development and commercialization milestone payments (1 1/1) Cardium Therapeutics Inc.* Schering AG (Germany) Cardium acquired a portfolio of cardiovascular growth factor therapeutic candidates Terms of the deal were not disclosed; the deal was made concurrently with a merger and financing by Cardium (10/20) Cellectis SA* (France) Shire Pharmaceuticals Group plc (UK) Shire got nonexclusive rights to site-directed genome engineering technologies The technology will be used to develop genetically engineered cells to produce certain gene-activated drugs; terms were not disclosed (12/20) Cellectis SA* (France) AstraZeneca plc (UK) AstraZeneca got nonexclusive rights to use homologous recombination technology AstraZeneca got rights to use the technology for manipulations of genetic material in rodents; terms were not disclosed (12/13) They extend partnership in target validation following successful pilot phase Cenix will use its high-throughput RNAi technology in up to six more projects to screen genes identified by Schering; terms were not disclosed (10/25) Cenix Schering AG BioScience (Germany) GmbH* (Germany) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 229 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Cephalon Inc. (CEPH) Pharma Co. (Country) Bausch & Lomb Inc. Type/Product Area Term/Details (Date) B&L got rights to develop ophthalmic products containing compounds that inhibit angiogenesis B&L is responsible for development; Cephalon would get a milestone payment upon acceptance of a drug application and would get royalties on sales (12/1) Cerimon Undisclosed Pharmaceuticals Japanese Inc.* company Cerimon acquired U.S. rights to two topical formulations of diclofenac Diclofenac is a non-steroidal anti-inflammatory drug; terms of the deal were not disclosed (10/26) Chromos Molecular Systems Inc. (Canada; TSE:CHR) Becton Dickinson and Co. BD got rights to patents related to expansion of antigen-specific T cells for a limited field of use Chromos gets license and maintenance fees and is eligible for milestone and royalty payments; the field of use was not disclosed (10/5) Corcept Therapeutics Inc. (CORT) Eli Lilly and Co. Lilly will support Corcept’s study of Corlux, a GR-II antagonist, to mitigate weight gain associated with use of olanzapine Lilly will supply olanzapine and pay for the study, which will explore the mechanism of action of GR-II antagonists for mitigating weight gain associated with atypical antipsychotic medications (10/21) Crucell NV (the Netherlands; CRXL) and DSM Biologics (the Netherlands) Ferring Pharmaceuticals A/S (Denmark) Ferring got rights to use the PER.C6 cell line in production of a specific protein in the field of women’s health Terms of the deal were not disclosed (12/21) Crucell NV (the Netherlands; CRXL) DSM Biologics (the Netherlands) Agreement to expand development of their PER.C6 protein and monoclonal antibody licensing business They plan to develop an integrated solution for producing recombinant products on the cell line; they have been working together since 2002 (12/20) Crucell NV (the Netherlands; CRXL) Tibotec Pharmaceuticals Ltd. (unit of Johnson & Johnson) Tibotec got nonexclusive rights to use the PER.C6 cell line for research in the field of virology Crucell is entitled to a license fee, annual maintenance fees and milestone payments; further terms were not disclosed (1 1/23) Curis Inc. (CRIS) Centocor Inc. (unit of Johnson & Johnson) Curis will perform screening and other work for Centocor’s BMP-7 program Centocor previously licensed the bone morphogenetic pathway technology from Curis; Centocor has an option to license resulting products (12/15) Curis Inc. (CRIS) Wyeth Wyeth extended the research term on their collaboration by one year, through Feb. 9, 2007 The January 2004 deal focuses on Hedgehog agonists, primarily in neurology; Curis is entitled to additional research funding (1 1/21) Collaboration to obtain biodefense-related federal contracts Contract calls for them to compete for federal research projects; terms were not disclosed (12/27) CytoGenix Fast Trak Inc. (OTC BB:CYGX) BioDefense (unit of GE Healthcare) 230 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Cytomedix Inc. (AMEX:GTF) COBE Cardiovascular Inc. (unit of the Sorin Group; Italy) COBE licensed all rights to the “Knighton” patent of autologous platelet releasate therapies for healing purposes Cytomedix gets an up-front royalty payment and is entitled to royalties of 7.5% and 1.5% on sales of disposable products and hardware products, respectively (10/10) Cytori Therapeutics Inc. (FSE:XMP) Olympus Corp. They formed a 50-50 joint venture to develop systems for stem cell and regenerative cell therapies They intend to develop devices based on Cytori’s Celution System; Olympus will contribute device technology and $30M to the venture; Cytori gets $1 1M up front and a potential $1 1M milestone payment (1 1/4) Depomed Inc. (DEPO) Madaus Srl (Italy) Madaus got exclusive rights to commercialize the antibiotic ProQuin XR in Europe Madaus is responsible for gaining approvals in Europe; specific terms were not disclosed (1 1/29) Discovery Laboratories Inc. (DSCO) Chrysalis Technologies (unit of Philip Morris USA Inc.) Deal to develop and market aerosolized surfactant replacement therapies for treating respiratory conditions Discovery gets rights to Chrysalis’ aerosolization technology for use with pulmonary surfactants; Chrysalis is entitled to royalties on resulting sales (12/1 1) Discovery Partners International Inc. (DPII) Mitsubishi Pharma Corp. (Japan) Deal to discover lead compounds for a therapeutic target selected by Mitsubishi Terms and the therapeutic focus of the deal were not disclosed (10/26) Discovery Partners International Inc. (DPII) Ono Pharmaceutical Co. Ltd. (Japan) DPI will work on multiple hit-to-lead and lead optimization projects for Ono Financial terms and the therapeutic focus were not disclosed (10/24) Domantis Ltd.* (UK) Bristol-Myers Squibb Co. Collaboration to develop Domain Antibody therapeutics in the fields of immunology and oncology Domantis gets $9.2M in up-front and research payments; it could get milestone payments of up to $20M per product, as well as royalties on sales; two existing Domantis programs are included (12/5) Epitomics Inc.* Hoffmann-La Roche Inc. Roche licensed rabbit monoclonal antibody technology, for use in discovery and development of antibodies for cancer and other diseases Epitomics is entitled to milestone payments and royalties on sales of products developed from the RabMab technology (10/18) EvoGenix Ltd. (Australia; ASX: EGX) GlaxoSmithKline plc (UK) Deal to apply EvoGenix’s EvoGene technology to compounds in GSK's pipeline EvoGenix gets research funding for up to three projects and is eligible to receive milestone and royalty payments on resulting products (10/6) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 231 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Evotec AG (Germany; FSE:EVT) Boehringer Ingelheim GmbH (Germany) Evotec will work to identify promising hit molecules from each company’s compound library The fee-for-services deal expands the scope of an existing collaboration; BI will develop any resulting compounds (1 1/3) Exelixis Inc. (EXEL) Wyeth Wyeth got rights to compounds targeting the farnesoid X receptor, a nuclear hormone receptor implicated in certain metabolic and liver disorders Exelixis gets $10M up front and up to $147.5M in development and commercialization milestone payments, as well as royalties on any sales (12/22) Exelixis Inc. (EXEL) Bristol-Myers Squibb Co. Collaboration to develop therapies targeted against the liver X receptor, which is implicated in cardiovascular and metabolic disorders Exelixis gets $17.5M up front and could get development and regulatory milestones of $140M per product for up to two products; it also could get sales milestones and royalties on resulting sales (12/6) ExonHit Therapeutics SA* (France) BioMerieux SA (France) They extended for six years a deal to develop blood diagnostics in the area of early cancer detection ExonHit gets R&D funding for each cancer studied; there will be at least five research programs; ExonHit also is entitled to milestone and royalty payments on resulting products (10/13) Genaissance Sankyo Co. Ltd. Pharmaceuticals (Japan) Inc. (GNSC) Genaissance will apply its HAP Technology to discover genetic markers of drug response for Sankyo Genaissance will receive license and other fees from Sankyo and has certain rights to share ownership of companion genetic tests (10/3) Genedata AG (Switzerland) F. Hoffmann-La Roche Ltd. (Switzerland) Multiyear expansion of their deal now includes all Roche high-throughput screening facilities in North America and Europe Roche will use Genedata Screener technology to estimate biological potency of compounds; terms were not disclosed (12/19) Gene Logic Inc. (GLGC) F. Hoffmann-La Roche Ltd. (Switzerland) Deal to reposition and develop multiple Roche drug candidates for which development had ended in Phase II or III trials Gene Logic can earn milestone and royalty payments on each candidate returned to clinical development; it also could license candidates not pursued by Roche (12/8) Genesis Harlan Bioventures Bioproducts for Inc. (OTC BB:GBIW) Science Inc. Harlan will help develop monoclonal antibodies for use in the Mammastatin Serum Assay Harlan will work with Genesis subsidiary Biomedical Diagnostics LLC in the effort; terms were not disclosed (1 1/22) Gen-Probe Inc. (GPRO) BioMerieux exercised a second option to develop diagnostic products using Gen-Probe’s ribosomal RNA technologies The diagnostic focus was not disclosed; Gen-Probe gets a $2.1M license fee and would get royalties on resulting sales (12/22) 232 BioMerieux SA (France) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) GlycoFi Inc.* Merck & Co. Inc. Deal to apply GlycoFi’s platform to produce and optimize a range of Merck’s biologic drug candidates GlycoFi gets an up-front cash payment and equity investment, research funding and potential milestone and royalty payments (12/12) GlycoFi Inc.* Eli Lilly and Co. Collaboration to discover and develop antibodies and other therapeutic proteins using GlycoFi's protein optimization technology They will initiate 10 protein optimization programs over the extendable two-year research term; GlycoFi gets an up-front payment, an equity investment and is entitled to milestone and royalty payments on resulting products (10/03) GTC Biotherapeutics Inc. (GTCB) LEO Pharma A/S (Denmark) LEO got rights to GTC’s recombinant form of human antithrombin, ATryn, in Europe, the Middle East and Canada GTC gets $2M up front and is entitled to milestone payments of up to $71M, as well as royalties on any resulting sales (1 1/1) GW Almirall Pharmaceuticals Prodesfarma plc (UK; LSE:GWP) SA (Spain) Almirall got rights to market Sativex in Europe (excluding the UK) GW gets £12M (US$21M) up front and up to £34M in milestone payments; the drug is in Phase III trials in three indications (12/12) HistoRx Inc.* Collaboration to apply the HistoRx AQUA platform for quantitative pathology analysis The goal is to develop proteomic information to elucidate pathway data; terms of the deal were not disclosed (10/13) Iconix Eli Lilly and Co. Pharmaceuticals Inc.* Lilly gained access to Iconix's chemogenomics technology Lilly will use the technology to prioritize and select drug candidates and to improve understanding of new compounds; terms of the deal were not disclosed (1 1/17) Incyte Corp. (INCY) Pfizer Inc. Pfizer got exclusive rights to Incyte’s CCR2 antagonist compounds, the most advanced of which is in Phase IIa trials Incyte gets $40M up front, research funding and will get $20M from the sale of interest-free convertible notes to Pfizer; it also could earn up to $743M in milestones, and royalties on sales; Incyte retains rights in multiple sclerosis and one undisclosed indication (1 1/21) InforSense Ltd.* (UK) AstraZeneca plc (UK) AstraZeneca got rights to InforSense technology through a new multiyear licensing deal AstraZeneca has been using the InforSense integrative analytics platforms since 2001; terms of the expanded deal were not disclosed (12/15) Inpharmatica Ltd.* (UK) Schering AG (Germany) Collaboration to prioritize proteins as drug targets Schering got rights to use Inpharmatica’s Biopendium and Chematica technologies; terms were not disclosed (10/17) Eli Lilly and Co. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 233 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) InterMune Inc. (ITMN) Valeant Pharmaceuticals International Inc. Valeant acquired U.S. and Canadian rights to the approved hepatitis C drug Infergen InterMune gets an up-front cash payment of $1 13.5M, about $2M in 2007, and up to $20M in milestone payments (1 1/28) Introgen Therapeutics Inc. (INGN) Colgate-Palmolive Co. Deal to develop products to help prevent precancerous conditions of the oral cavity and oral cancer Introgen will focus on oral formulations of some of its therapeutics that use tumor suppressors; Colgate purchased $20M in Introgen stock for priority rights; further terms were not disclosed (1 1/7) Invitrogen Corp. (IVGN) Procter & Gamble Pharmaceuticals Inc. They extended an RNAi research service agreement through 2006 Invitrogen is using its technologies to help P&G’s target identification and validation programs; terms were not disclosed (1 1/1) Jerini AG (Germany; FSE:JI4) Kos Pharmaceuticals Inc. Deal for the development and marketing in North America of Jerini’s Icatibant for hereditary angioedema and other diseases Jerini gets $15M up front and a $12M equity investment; it also is entitled to milestone payments and royalties on any resulting sales (1 1/7) Labopharm Inc. (Canada; TSE:DDS) Recordati SpA (Italy) Recordati got exclusive rights to market Labopharm’s once-daily tramadol product in the UK They anticipate launching the analgesic in the UK in 2006; Labopharm is entitled to an up-front payment, milestone payments and royalties on sales (1 1/16) LifeSpan BioSciences Inc.* Pfizer Inc. Pfizer gained access to all features of LifeSpan’s DrugTarget Database As part of the deal, Pfizer will nominate at least 60 new targets to be studied by immunohistochemistry and published in the consortium database (12/21) Maxygen Inc. (MAXY) Hoffmann-La Roche Inc. Deal to develop Maxygen’s recombinant factor VIIa products for multiple indications They will share R&D costs; Maxygen retained certain commercialization rights; Maxygen could receive $95M in the deal, plus royalties on sales (12/15) MediGene AG (Germany; FSE:MDG) Glaxo Group Ltd. (UK) Glaxo got nonexclusive rights to technology resulting from MediGene’s program to develop a cancer vaccine MediGene gets an undisclosed one-time payment in the deal; specific technology details were not disclosed (12/19) MedImmune Inc. (MEDI) BioWa Inc. (unit of Kyowa Hakko Kogyo Co. Ltd.; Japan) MedImmune got rights to use Potelligent technology for enhancing antibodydependent cellular cytotoxicity BioWa gets technology access fees, and could receive milestone payments and royalties on resulting products (12/7) Deal to discover and develop drugs derived from natural products chemistry MerLion will identify chemical seeds from targets provide by Astellas; MerLion would be entitled to milestone and royalty payments on resulting compounds (10/4) MerLion Astellas Pharmaceuticals Pharma Inc. Pte. Ltd. (Japan) (Singapore) 234 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Monogram Biosciences Inc. (MGRM) Merck KGaA (Germany) Monogram will perform colorectal cancer biomarker studies for Merck The goal is to identify patients who most likely would benefit from Erbitux treatment; Monogram, formerly ViroLogic Inc., will receive undisclosed payments (10/24) MorphoSys AG (Germany; FSE:MOR) Merck & Co. Inc. Merck got rights to use HuCAL GOLD and AutoCAL technologies for antibody development MorphoSys gets an up-front payment, annual user fees and R&D funding under the five-year license; it also could get license, milestone and royalty payments on resulting products (12/14) MorphoSys AG (Germany; FSE:MOR) Bayer Pharmaceuticals Corp. Bayer gained access to the HuCAL GOLD antibody library under a five-year extension of their collaboration At least three new antibody development programs will be started in 2006, and up to 25 in all if the deal runs its full course; MorphoSys gets user fees, R&D funding and potential license, milestone and royalty payments (12/8) MorphoSys AG (Germany; FSE:MOR) Schering AG (Germany) They added three programs to existing collaboration, and Schering got eight licenses for in vivo diagnostic applications The three added programs cover antibody development; MorphoSys is entitled to license payments (10/10) Myriad Genetics Inc. (MYGN) Abbott Laboratories They extended a collaboration in pharmacogenetics Abbott is funding work to identify genetic variation around drug targets in various stages of development (1 1/22) Neose Technologies Inc. (NTEC) Novo Nordisk A/S (Denmark) They expanded 2003 deal under which Novo is using Neose’s GlycoPEGylation technology Novo is developing a next-generation version of a protein it markets; Neose is entitled to further R&D funding and an increased milestone potential (12/15) Nephrogen LLC* Gambro AB (Sweden) Collaboration focused on restoring kidney function using adult stem cells They initially will target acute renal failure in the three-year deal; terms were not disclosed (10/24) Neurome Inc.* Wyeth They expanded deal focused on drug discovery for neurodegenerative diseases Neurome now will evaluate drug candidates as part of intervention studies in an animal model; terms were not disclosed (1 1/21) NexMed Inc. (NEXM) Undisclosed Japanese company Agreement to develop a new fentanyl patch product for treating severe chronic pain NexMed got $0.1M up front and could get milestone payments; it retains certain commercialization rights (1 1/3) NicOx SA (France; Eurolist:NICOX) Pfizer Inc. Pfizer exercised its option to acquire exclusive rights to nitric oxide-donating compounds in ophthalmology NicOx received €2M, and potentially could receive €33M more, as well as royalties on any sales (1 1/22) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 235 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) NicOx SA (France; Eurolist:NICOX) Pharma Co. (Country) Term/Details (Date) They extended August 2003 deal to evaluate NicOx nitric oxide-donating compounds in an undisclosed indication The deal also was broadened to an additional compound class; NicOx gets an undisclosed payment in connection with the deal’s extension (1 1/2) Novation Novartis AG Pharmaceuticals (Switzerland) Inc.* (Canada) Deal for the discovery of oral RNA-directed therapeutics Novation is providing use of its Quest assays in the deal; terms were not disclosed (1 1/23) Novavax Inc. (NVAX) Esprit Pharma Inc. Esprit is getting rights to market Estrasorb (estradiol topical emulsion) in North America Novavax will get $12.5M within one year, as well as royalties on sales and milestone payments if certain sales levels are reached (10/18) OncoMethylome Sciences SA* (Belgium) Schering-Plough Corp. Schering-Plough got rights to use assay technology that measures the methylation status of the MGMT gene The goal is to optimize Temodar therapy in treating patients with glioblastoma multiforme; OncoMethylome is entitled to an upfront fee, milestone payments and sample processing fees (1 1/16) OncoTherapy Science Inc.* (Japan) BioWa Inc. (subsidiary of Kyowa Hakko Kogyo Co Ltd.; Japan) Collaboration to identify and develop cancer-focused monoclonal antibodies They will carry out R&D collaboratively and would share any resulting profits (10/24) OSI Undisclosed Pharmaceuticals British company Inc. (OSIP) The unnamed firm got nonexclusive rights from OSI’s UK subsidiary relating to dipeptidyl peptidase IV patents The patents cover the use of DPIV inhibitors for treating Type II diabetes and related indications; OSI is entitled to up-front, milestone and royalty payments (12/22) Oxford BioMedica plc (UK; LSE:OXB) Undisclosed company The unnamed company got a license to OXB’s LentiVector gene delivery system for research purposes Oxford BioMedica gets an up-front license payment and an annual maintenance fee; further terms were not disclosed (10/24) Oxford BioMedica plc (UK; LSE:OXB) Sigma-Aldrich Corp. Deal under which SigmaAldrich will commercialize OXB’s LentiVector technology for the reagent and research tool market Oxford BioMedica will receive an up-front payment, annual minimum payments and royalties on sales; it also will get a $5M equity investment; Sigma-Aldrich also gets first rights to develop products based on OXB’s EIAV-based LentiVector technology (10/20) Oxford Genome Sciences Ltd.* (UK) UCB Group SA (Belgium) UCB licensed rights to the Oxford Genome Anatomy Project database The database is used to discover and validate drug targets and biomarkers; terms of the deal were not disclosed (10/18) 236 Merck & Co. Inc. Type/Product Area BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Pain Therapeutics Inc. (PTIE) King Pharmaceuticals Inc. Deal to develop and market PTI’s Remoxy and other abuse-resistant opioid painkillers PTI gets $150M up front and up to $150M in milestone payments; King is expected to fund $100M of development costs; a pivotal trial of Remoxy (long-acting oxycodone) is expected to start in January (1 1/10) PDL BioPharma Inc. (PDLI) Merck & Co. Inc. Merck got nonexclusive rights under PDL’s humanization patents to develop antibodies against two antigens PDL is entitled to an up-front licensing payment, development milestones and royalties on any sales; the antigens were not disclosed (12/3) Perlegen Sciences Inc.* Pfizer Inc. Four-year deal for wholegenome and replication studies to identify genes associated with diseases and to predict patient responses to certain drugs Perlegen gets research payments; the companies will share in certain resulting intellectual property rights; the deal followed by one day a $50M equity investment in Perlegen by Pfizer; they have been partners since 2002 (12/28) Perlegen Sciences Inc.* Merck & Co. Inc. Deal to perform a highdensity whole-genome analysis of more than 1,000 individuals Perlegen will assay genetic variations in DNA samples provided by Merck; terms of the deal were not disclosed (10/04) Plureon Corp.* Becton Dickinson and Co. Deal for diabetes research and development using Plureon's stem cell technology BD will sponsor Plureon research for up to three years and be responsible for further development; further terms were not disclosed (10/14) PPD Inc. (PPDI) Falco Biosystems Ltd. (Japan) PPD will seek to discover biomarkers for a renal cell carcinoma diagnostic test PPD will own resulting technology; Falco will get a license to resulting technology in certain countries; terms were not disclosed (12/7) Progenics Wyeth Pharmaceuticals Inc. (PGNX) Deal to develop and market Progenics’ Phase III product methylnaltrexone (MNTX) for treating opioid-induced side effects Progenics gets $60M up front and up to $356.5M in milestone payments, as well as royalties on any sales; Progenics also retained a U.S. co-promotion option (12/23) Prolexys GlaxoSmithKline Pharmaceuticals plc (UK) Inc.* GSK got nonexclusive rights to the Prolexys Human Interactome Database The database contains more than 258,000 human protein-protein interactions; terms of the deal were not disclosed (10/3) Protein Design Labs Inc. (PDLI) Expanded deal to develop and sell daclizumab (Zenapax) for organ transplant patients now covers a subcutaneous formulation made by PDL PDL gets $10M up front and may be eligible for milestone payments of up to $145M; they will share development costs; PDL has a co-promotion option in the U.S. and would get royalties on sales elsewhere (1 1/1) Hoffmann-La Roche Inc. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 237 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Protherics plc (UK; LSE:PTI) AstraZeneca plc (UK) AstraZeneca got rights to the sepsis product CytoFab, which is nearing a Phase III trial Protherics gets £1 6.3M ($29M) up front and a £7.5M equity investment; milestone payments could total £1 7 1M ($304); Protherics would get royalties of 20% (12/8) pSivida Ltd. (Australia; PSDV) Beijing Med-Pharm Corp. Beijing Med-Pharm got rights to pSivida’s BrachySil cancer product in China Beijing Med-Pharm will be responsible for development and marketing in China; terms were not disclosed (10/26) PTC Therapeutics Inc.* Bausch & Lomb Inc. B&L got an option to exclusively license certain PTC compounds for use in ophthalmology indications The compounds are from PTC’s anti-angiogenesis program; terms of the deal were not disclosed (12/1) Radius* (formerly Nuvios) Ipsen SA (France) Radius got worldwide rights except in Japan to BA058 and its analogues, along with rights to formulation technologies BA058 is an analogue of parathyroid hormone-related protein in Phase I trials for osteoporosis; Ipsen gets up-front and potential milestone and royalty payments (12/13) Regeneron Sanofi-Aventis Pharmaceuticals Group (France) Inc. (REGN) They broadened collaboration on the VEGF Trap program to include Japan; the deal now is worldwide, excluding intraocular delivery to the eye Regeneron gets $25M up front, as well as potential milestone and royalty payments under the expansion (12/22) Rubicon Genomics Inc.* Abbott Laboratories Deal to develop and market Rubicon’s MethylPlex methylation detection technology for diagnosis and prognosis of cancers Rubicon will work with Abbott Molecular in the multiyear deal, terms of which were not disclosed (10/31) Saneron CCEL Therapeutics Inc.* GE Healthcare Collaboration on optimizing GE’s Ficoll-Pacque for isolating stem cells from cord blood Terms of the deal were not disclosed (1 1/21) Sareum Holdings plc (UK; AIM:SAR) Schering AG (Germany) Sareum will use its technologies to show how drug candidates interact with their target protein receptors Sareum is entitled to receive research fees and potential milestone payments (10/27) Scil Technology Holding GmbH* (Germany) F. Hoffmann-La Roche Ltd. (Switzerland) Scil acquired worldwide rights to the growth factor MIA/CDRAP from Roche Diagnostics Roche licensed back rights to CD-RAP for use in research diagnostics; terms of the deal were not disclosed (10/10) Scolr Pharma Inc. (AMEX:DDD) Wyeth Consumer Healthcare Wyeth got rights to use Scolr’s CDT delivery platform in an over-the-counter formulation Scolr gets an up-front licensing fee and could get milestone and royalty payments (12/22) 238 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Term/Details (Date) Scynexis Inc.* Teijin Pharma Ltd. (Japan) Scynexis will provide medicinal and analytical chemistry services for Teijin research programs Terms of the deal were not disclosed (10/13) SkyePharma plc (UK; SKYE) Maruho Co. Ltd. (Japan) Maruho got rights to develop and market the anesthetic DepoBupivacaine in Japan SkyePharma is entitled to up to $18M in upfront and milestone payments, as well as royalties on any resulting sales (1 1/1) Sonus Schering AG Pharmaceuticals (Germany) Inc. (SNUS) Schering got worldwide rights to Sonus’ Tocosol Paclitaxel, a cancer product in Phase III trials Schering made a $15M equity investment, buying 3.9M shares; Sonus also got an upfront license fee of $20M and could get regulatory milestone payments of up to $132M, as well as sales royalties and sales milestones (10/18) Syntonix Boehringer Pharmaceuticals Ingelheim GmbH Inc.* (Germany) Deal to optimize certain BI peptides for inhalation, using Syntonix’s SynFusion and Transceptor technologies Syntonix gets an up-front fee and research support, and could get milestone and royalty payments on any resulting products; the deal could be worth $63M (10/21) Targacept Inc.* AstraZeneca plc (UK) Deal to develop and market Targacept’s Phase II drug TC-1734 for Alzheimer’s disease and other cognitive disorders Targacept gets $10M up front, $26M in research funding, and $20M if AstraZeneca starts a Phase II program; Targacept also could earn about $244M in milestone payments and double-digit royalties on sales (12/28) Theravance Inc. (THRX) Astellas Pharma Inc. (Japan) Deal to develop and market Theravance’s antibiotic telavancin, which is in Phase III trials Theravance gets $65M up front and up to $156M in clinical and regulatory milestone payments; it would get royalty rates ranging from the high-teens to the high-20s (1 1/7) Tm Bioscience Corp. (Canada; TSE:TMC) Abbott Laboratories Nonexclusive license deal covering certain technology in human and pathogen genotyping and other areas The license covers Tm’s current and future products in all fields of use; further details were not disclosed (10/3) TorreyPines Therapeutics Inc.* Eisai Co. Ltd. (Japan) Collaboration to discover genes responsible for lateonset Alzheimer’s disease The deal continues Eisai’s support for the program that began in 2001; TorreyPines gets a signing fee and research support; Eisai gets first negotiation rights on any resulting gene targets (10/1 1) TransTech Pharma Inc.* Boehringer Ingelheim GmbH (Germany) BI got rights to develop compounds directed at an undisclosed target of interest to both companies TransTech gets an up-front payment, research support and potential milestone payments in a deal worth up to $54M; it also would get royalties on sales (12/21) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 239 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Type/Product Area Terms/Details (Date) Vernalis plc (UK; VNLS) Mylan Laboratories Inc. Vernalis acquired North American rights to Apkyn, a marketed product for treating hypomobility The condition is associated with Parkinson’s disease; Vernalis paid $23M in cash for the exclusive rights (1 1/4) Vernalis plc (UK; VNLS) Britannia Pharmaceuticals Ltd. (UK) Deal to develop new formulations of apomorphine in North America for treating Parkinson’s disease Vernalis got rights to use Britannia technology to develop a continuous subcutaneous infusion of apomorphine and to negotiate a deal on a nasal powder formulation (1 1/4) Vertex GlaxoSmithKline Pharmaceuticals plc (UK) Inc. (VRTX) GSK got rights to develop VX-409, a sodium channel modulator for treating pain, and backup compounds Vertex gets $20M up front and up to $385M in development and sales milestone payments, as well as royalties on any resulting sales (12/14) Xceleron Ltd.* (UK) Servier SA (France) Xceleron will provide accelerator mass spectrometry services to Servier The AMS technology will be used to help accelerate drug discovery and development; terms of the one-year deal were not disclosed (12/7) Xenogen Corp. (XGEN) Novartis AG (Switzerland) They extended for two years deal under which Novartis licensed Xenogen software Novartis will continue to use the Living Image Software and methods of biophotonic imaging; the original deal was signed in 2000 (12/7) XenoPort Inc. (XNPT) Astellas Pharma Inc. (Japan) Astellas got rights in Japan and elsewhere in Asia to the Phase II CNS agent XP13512, a prodrug of gabapentin XenoPort gets a license payment of $25M and could get up to $60M in milestone payments, as well as mid-teen royalty rates on product sales in the territory (1 1/30) YM BioSciences Inc. (Canada; TSE:YM) Innogene Kalbiotech Ltd. (Singapore) Innogene, a unit of PT Kalbe Farma Tbk, got certain rights to the EGFR-targeting monoclonal antibody nimotuzumab YM subsidiary CimYM gets $1M up front and potential milestone and royalty payments; Innogene gets rights in Singapore, Taiwan, Thailand, Indonesia, Malaysia, the Philippines, South Africa and other markets (1 1/17) Znomics Inc.* Merck & Co. Inc. Deal to discover and characterize drug targets for metabolic diseases They will use Znomics’ zebrafish technology in the deal, terms of which were not disclosed (12/5) 240 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: New Agreements (Continued) Notes: # The information in the chart does not cover agricultural agreements or those between biotech companies. * Private companies are indicated with an asterisk. Unless otherwise noted, stock symbols listed are on the Nasdaq market. AIM = Alternative Investment Market; AMEX = American Stock Exchange; ASX = Australian Stock Exchange; ATX = Austrian Stock Exchange; CDNX = Canadian Venture Exchange; FSE = Frankfurt Stock Exchange; LSE = London Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; SWX = Swiss Stock Exchange; TSE = Toronto Stock Exchange; VSE = Vancouver or Vienna Stock Exchange. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 241 2005 Biotech-Big Pharma Collaborations: Modified And Terminated Agreements I. MODIFIED AGREEMENTS Biotech Co.* (Country; Symbol) Pharma Co. (Country) Change from original agreement Terms/Details (Date) Alliance LEO Pharma Pharmaceutical A/S (Denmark) Corp. (OTC BB:ALLP) LEO gained extra time to decide if it will license rights to Oxygent in Europe and Canada The evaluation period was extended until six days after Alliance submits to LEO results of a proof-of-concept study in surgery patients (3/2) Atugen AG* (Germany) Altana Pharma AG (Germany) They renewed nonexclusive target validation and license agreement for another year Atugen validates molecular targets, and Altana gets a license to use Atugen’s gene silencing and oligonucleotide delivery technologies (2/16) BioTie Therapies Oyj (Finland; HEX:BTH1V) Sanofi-Aventis Group (France) They will negotiate an extension to an option deal for evaluation of BioTie’s bioheparin product The one-year deal was set to expire when they decided to negotiate an extension; terms were not disclosed (3/31) ComGenex Inc.* (Hungary) Bayer Healthcare AG (Germany) The companies extended their exclusive chemistry collaboration for a seventh year ComGenex will continue to provide chemistry services to support drug discovery at Bayer; terms were not disclosed (3/1) Cubist Eli Lilly and Co. Pharmaceuticals Inc. (CBST) Cubist is purchasing a 2% reduction in royalties payable to Lilly on sales of Cubicin Cubist paid Lilly about 1.88M shares (worth about $20M); Cubicin had acquired rights to the product in 1997 (3/3) Exelixis Inc. (EXEL) GlaxoSmithKline plc (UK) They modified October 2002 deal covering development of drugs in vascular biology, inflammatory disease and oncology The amendment provides accelerated milestone payments to Exelixis and allows third-party development and funding of certain programs; GSK retains exclusivity rights to 32 specified targets (1/10) Halozyme Therapeutics Inc. (AMEX:HTI) Baxter Healthcare Corp. They expanded relationship by signing a development and supply agreement for Halozyme’s Enhanze SC The product, a recombinant human hyaluronidase enzyme, was the subject of an August 2004 partership for selling the product in the U.S. (3/30) Immunicon Corp. (IMMC) Veridex LLC (unit of Johnson & Johnson) Amended 2000 deal changes the triggering events for milestone payments to Immunicon They are working on two cancer programs; the milestone totals remained the same (2/3) FIRST QUARTER 242 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: Modified And Terminated Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Change from original agreement Terms/Details (Date) Ligand Eli Lilly and Co. Pharmaceuticals Inc. (LGND) Ligand exercised its first option to buy down a portion of royalties payable to Lilly on U.S. sales of Ontak Ligand paid $20M in exchange for elimination of royalties due on sales in 2005 and a reduced reverse-tiered royalty scale on later sales above a certain threshold (1/7) MedImmune Inc. (MEDI) GlaxoSmithKline plc (UK) MedImmune may receive milestone and royalty payments under revised terms on a deal related to a human papillomavirus vaccine that Merck & Co. Inc. has in Phase III development MedImmune also may get milestones and royalties from an HPV vaccine it co-developed with GSK; GSK had granted Merck certain HPV rights under a 1997 deal with MedImmune (2/2) Metabasis Therapeutics Inc.* Merck & Co. Inc. They extended and expanded a December 2003 collaboration in hepatitis C Merck will continue to fund through December 2005 Metabasis’ efforts to apply its technologies to Pfizer preclinical candidates (1/25) MorphoSys AG (Germany; FSE:MOR) Bristol-Myers Squibb Co. BMS gained further access to MorphoSys’ HuCAL GOLD library for use in discovery programs BMS previously had a nonexclusive license to prior versions of the HuCAL library and the AutoCAL system; terms were not disclosed (1/26) Regeneron Sanofi-Aventis Pharmaceuticals Group (France) Inc. (REGN) The rights to develop VEGF Trap for eye diseases reverted to Regeneron Sanofi, which is continuing development in oncology, made a final $25M payment related to the program in eye diseases, half of which would be repayable upon commercialization (1/10) SkyePharma plc (UK; SKYE) They extended May 2004 deal on Skye’s formulation of fenofibrate The amendment would allow First Horizon to launch the product in the first half of 2005, pending FDA approval; details were not disclosed (2/1) Sunesis Johnson & Johnson Pharmaceuticals Pharmaceutical Inc.* Research & Development LLC They extended through 2005 their collaboration on smallmolecule enzyme inhibitors targeting Cathepsin S Sunesis gets research funding and potential milestone and royalty payments under the deal, originally signed in May 2002 (1/10) Vicuron Pfizer Inc. Pharmaceuticals Inc. (MICU) March 1999 collaboration to develop next-generation oxazolidinones was extended for another year The goal is to develop oral antibiotics; terms of the extension were not disclosed (3/30) They extended chemistry agreement signed in May 2004 for another year Evotec is supporting medicinal chemistry programs at Roche under undisclosed terms (4/13) First Horizon Pharmaceutical Corp. SECOND QUARTER Evotec OAI AG (Germany; FSE:EVT) F. Hoffmann-La Roche Ltd. (Switzerland) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 243 2005 Biotech-Big Pharma Collaborations: Modified And Terminated Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Change from original agreement Terms/Details (Date) Gen-Probe Inc. (GPRO) Bayer HealthCare LLC Tentative arbitration ruling said Gen-Probe is entitled to coexclusive rights to distribute qualitative TMA assays to detect the hepatitis C virus and HIV-1 Bayer previously held all rights; the arbitrator also determined the collaboration should be terminated, which would give Gen-Probe the right to develop and market certain viral assays (4/5) Gene Logic Inc. (GLGC) Daiichi Pharmaceutical Co. Ltd. (Japan) Daiichi continued its subscription to the BioExpress System The focus of the multiyear subscription is primarily for discovery research; terms of the deal were not disclosed (6/7) Gene Logic Inc. (GLGC) Takeda Pharmaceutical Co. Ltd. (Japan) Takeda extended its subscription to the BioExpress System Takeda extended access through 2006 for use in drug discovery and development; terms of the deal were not disclosed (6/7) Gilead Sciences Inc. (GILD) Hoffmann-La Roche Inc. Gilead is seeking to terminate a 1996 agreement on the influenza product Tamiflu Gilead is alleging material breach of the agreement, and wants to regain all rights to the product held by Roche (6/23) GW Bayer HealthCare Pharmaceuticals AG (Germany) plc (UK; LSE:GWP) They amended marketing deal on Sativex in the UK and Canada, after the product was approved in Canada first Some details were changed, but milestone payments of £32.75M due to GW remain unchanged (5/1 1) Indevus Pliva d.d. Pharmaceuticals (Croatia) Inc. (IDEV) Saturn Pharmaceuticals Inc. acquired rights to market Sanctura from Odyssey Pharmaceuticals Inc. Odyssey, a Pliva subsidiary, had acquired rights in April 2004; Indevus gets enhanced economic terms under the amended deal (5/16) Ligand Eli Lilly and Co. Pharmaceuticals Inc. (LGND) Ligand exercised its final option to buy down a further portion of royalties due Lilly on U.S. sales of Ontak Ligand will pay Lilly $13M in exchange for elimination of royalties due on sales in the U.S. in 2006, and a reduced, reverse-tiered royalty scale on sales of the cancer drug thereafter (4/7) Oscient LG Life Pharmaceuticals Sciences Ltd. Corp. (OSCI) (South Korea) Amended agreement includes a reduction of future royalties payable to LG for Factive sales at certain levels Oscient will make a $2M payment to LG; the modified deal also calls for an $8M increase in milestone payments to LG at certain sales thresholds (4/6) Peakdale Molecular Ltd.* (UK) GlaxoSmithKline plc (UK) Peakdale will provide chemistry services to GSK through 2005 under an extension of an existing agreement Peakdale chemists have worked with GSK since 2002; terms of the deal were not disclosed (4/24) Qiagen Nv (the Netherlands; QGEN) Abbott Laboratories Abbott got distribution rights to a number of PCR diagnostic tests under an extension to an existing deal Abbott has nonexclusive distribution rights to certain Qiagen products; the PCR assays were developed by Artus GmbH, which Qiagen acquired (6/22) 244 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: Modified And Terminated Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Change from original agreement Terms/Details (Date) SkyePharma plc (UK; SKYE) GlaxoSmithKline plc (UK) They amended their deal concerning royalties on Paxil CR SkyePharma gets a one-time payment of $10M, and an increase in its royalty rate from 3% to 4%; GSK has been unable to supply Paxil CR in the U.S. since March 4, 2005, due to manufacturing issues (4/28) THIRD QUARTER Cytokinetics Inc. (CYTK) GlaxoSmithKline plc (UK) Amended agreement provides Cytokinetics an expanded role in development of SB-743921 Cytokinetics will lead and fund development in cerain hematological cancers and is entitled to additional milestone payments; GSK has an option to take over responsibility in those indications (9/27) DOV Pharmaceutical Inc. (DOVP) Merck & Co. Inc. They amended 2004 deal covering clinical development of DOV 21,947 and DOV 216,303, following early trial data on 21,947 Certain early stage clinical trials for DOV 21,947 now will be undertaken by DOV; DOV would be reimbursed if Phase II results of the depression candidate are successful (8/8) Epigenomics AG (Germany; FSE:ECX) Roche Diagnostics They extended a deal covering the development of five cancer diagnostic tests The R&D part of the collaboration was extended at least six months with the option to expand the deal; terms were not disclosed (9/30) Imcor GE Healthcare Pharmaceutical (UK) Co. (PK:ICPH) and Alliance Pharmaceutical Corp. (OTC BB:ALLP) They resolved disputed patent claims covering ultrasound contrast agents GE Healthcare will pay $1M to Imcor and $200,000 to Alliance in license fees; all parties granted the others nonexclusive, royalty-free cross-licenses with the right to sublicense their respective ultrasound contrast agents (9/22) Karo Bio AB (Sweden; SSE: KARO) Wyeth Pharmaceuticals They extended a deal signed in 2001 for an additional year They are working on new treatments for atherosclerosis by targeting the liver X receptor; terms were not disclosed (8/15) MedImmune Inc. (MEDI) Abbott Laboratories They amended U.S. co-promotion agreement on Synagis, a product for treating respiratory syncytial virus MedImmune will take full responsibility for product sales in the U.S. after June 2006; Abbott is entitled to a portion of sales and potential milestone payments (8/31) Memory Hoffmann-La Pharmaceuticals Roche Inc. Corp. (MEMY) Memory reacquired the rights to the PDE4 inhibitors MEM 1414 and MEM 1917, which Roche stopped developing for Alzheimer’s disease in April Roche has an option to continue development of the drugs after Phase II trials; Roche also maintains exclusive rights to all other drug candidates from Memory’s PDE4 inhibitor program (8/18) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 245 2005 Biotech-Big Pharma Collaborations: Modified And Terminated Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Change from original agreement Terms/Details (Date) Prima Biomed Ltd. (Australia; ASX:PRR) AstraZeneca plc (UK) They extended research deal on Fc receptor technology until June 30 The deal from October 2004 was made with Prima Biomed subsidiary Arthron Pty. Ltd.; AstraZeneca retains an option to license the technology (9/27) Senetek plc (OTC BB:SNTKY) Valeant Pharmaceuticals International Valeant got expanded distribution rights for Kinetin and exclusive worldwide rights to Zeatin Senetek will get minimum royalty payments of $37M through 2010 for the skincare product Kinetin (Kinerase), plus potential additional royalties (8/9) FOURTH QUARTER Actelion Ltd. (Switzerland; SWX:ATLN) UCB Pharma (Belgium) They replaced existing license deal covering the Gaucher’s disease product Zavesca Actelion assumes full responsibility for the pre-UCB obligations on manufacturing and supply, and clinical development; UCB gets an up-front payment in return for a singledigit royalty rate on future sales (1 1/17) Cambridge Antibody Technology plc (UK; CATG) Abbott Laboratories They reached an agreement regarding royalties payable to CAT under a licence agreement covering Humira CAT gets $255M, which it will pay to its licensors; it also gets five annual payments of up $9.375M; CAT’s royalty payments were reduced to 2.688% of sales from 5.1% (10/26) Cephalon Inc. (CEPH) Ranbaxy Laboratories Ltd. (India) They settled patent infringement dispute in the U.S. related to Provigil (modafinil) Ranbaxy got a nonexclusive, royalty-bearing right to market a generic version of the product starting in 201 1; they also entered a series of business arrangements related to modafinil (12/22) Cephalon Inc. (CEPH) Teva Pharmaceutical Industries Ltd. (Israel) They settled patent infringement disputes in the U.S. and UK related to Provigil (modafinil) Teva got a nonexclusive, royalty-bearing right to market a generic version of the product starting in 201 1; they also entered a series of business arrangements related to modafinil (12/9) CuraGen Corp. (CRGN) Bayer Pharmaceuticals Corp. They revised terms of deal in metabolic disorders relating to development of BAY 76-7171 (formerly CT052) CuraGen exercised its right to revert to a tiered royalty structure on any sales and no longer will contribute to development costs of the drug (12/20) Depomed Inc. (DEPO) Biovail Corp. (Canada) They resolved a dispute regarding a license agreement on the metformin-based diabetes product Glumetza Under the new deal, Depomed has rights to the product in the U.S.; Biovail relinquished its option to develop metformin combination products; Depomed withdrew legal action following the agreement (12/13) 246 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: Modified And Terminated Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Change from original agreement Terms/Details (Date) Enzon Sanofi-Aventis Pharmaceuticals Group (France) Inc. (ENZN) They amended license agreement covering the leukemia drug Oncospar Enzon will pay a single-digit royalty rate on annual sales that exceed $25M; it had been paying 25% on all sales; Sanofi gets an up-front cash payment of $35M (10/31) Genetic Technologies Ltd. (Australia; GENE) Applera Corp. The companies settled a patent dispute initiated by Gene Technologies in 2003 Terms were not disclosed but do include a license to the non-coding patents from Genetic Technologies (12/12) Gilead Sciences Inc. (GILD) F. HoffmannLa Roche Ltd. (Switzerland) They resolved a dispute related to their 1996 deal covering the influenza drug Tamiflu Gilead gets $62.5M in adjusted royalties, and will get sales royalties from 14% to 22%; Gilead also gets certain co-promotion options in the U.S.; the deal ends arbitration proceedings (1 1/16) Progenics UR Labs Inc. Pharmaceuticals Inc. (PGNX) Progenics acquired a substantial portion of the royalty and milestone rights to methylnaltrexone (MNTX) Progenics initially licensed rights to the drug from UR Labs in 2001; UR Labs received 686,000 Progenics shares and $2.6M in cash (12/23) Savient Barr Pharmaceuticals Pharmaceuticals Inc. (SVNTE) Inc. and NV Organon (the Netherlands) They settled patent litigation regarding Barr’s generic version of Mircette, an oral contraceptive product Barr paid Savient $13.75M, of which about $2.8M will be passed on to the inventor (12/2) II. TERMINATED AGREEMENTS Biotech Co.* (Country; Symbol) Pharma Co. (Country) Change from original agreement Terms/Details (Date) Advancis Pharmaceutical Corp. (AVNC) Par Pharmaceutical Corp. Par terminated a deal covering Advancis’ Amoxicillin Pulsys product The move followed a failed trial in strep throat; Par may be entitled to a portion of some future revenues (8/4) Aphton Corp. (APHT) Sanofi Pasteur (France) They ended a deal from 1997 to develop Aphton’s immunotherapy compound Insegia Aphton regained rights to the G1 7DT immunogen, which is being developed for cancers, and intends to find a new partner (1 1/9) Arqule Inc. (ARQL) Pfizer Inc. Pfizer is ending deal under which Arqule has been producing synthetic chemical compounds for Pfizer The deal, started in 2001, will end May 22, 2006; Arqule expects to receive $19.8M in connection with the termination notification (12/6) They ended December 2003 collaboration using molecular cytogenetics to identify and validate oncology targets The agreement expired as a result of Sanofi’s decision not to advance targets from the collaboration (12/21) Avalon Sanofi-Aventis Pharmaceuticals Group (France) Inc. (AVRX) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 247 2005 Biotech-Big Pharma Collaborations: Modified And Terminated Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Change from original agreement Terms/Details (Date) Biopure Inc. (BPUR) Tshepo Pharmaceuticals Ltd. They formally terminated deal under which Tshepo held South African rights for the oxygen therapeutic Hemopure Biopure appointed an interim registration holder and a marketing agent, and seeks to register itself as a pharmaceutical marketing company in South Africa so it can hold the product registration (2/1) BioTie Therapies Oyj (Finland; HSE: BTH1V) Sanofi-Aventis Group (France) Sanofi did not renew option agreement in deal to develop a oral heparin-like product BioTie plans to continue the recombinant heparin program with a new development partner (10/17) Cellegy PDI Inc. Pharmaceuticals Inc. (CLGY) Settlement of legal disputes over Cellegy’s Fortigel (testosterone gel) returned all rights to Cellegy Cellegy paid PDI $2M, issued a promissory note payable in 18 months, and issued to PDI a $3.5M convertible debenture due in three years (4/1 1) Discovery Partners International Inc. (DPII) Pfizer Inc. The companies terminated discussions regarding a potential new deal to replace existing one about to expire Discovery has received about $92M from the chemistry deal from 2002 to 2005; Discovery will reduce its combinatorial chemistry operations as a result (1 1/29) Dynavax Technologies Corp. (DVAX) UCB Farchim SA (Switzerland) They ended their collaboration on seasonal allergy products that began in February 2004 UCB will return all rights to the program to Dynavax, which plans to complete an ongoing Phase II/III trial of its AIC immunotherapy for ragweed allergy (3/18) Flamel Technologies SA (France; FLML) TAP Pharmaceutical Products Inc. TAP terminated a deal to use Flamel’s Micropump technology in the delivery of lansoprazole The compound is the active ingredient in TAP’s Prevacid; TAP intends to move forward with a different formulation (9/5) Flamel Technologies SA (France; FLML) Biovail Laboratories Inc. (Canada) Flamel terminated the license deal covering its long-acting acyclovir formulation, Genvir Biovail did not start trials in the time period called for under their February 2003 deal; Flamel intends to find another partner (3/3) Flamel Technologies SA (France; FLML) Bristol-Myers Squibb Co. They resolved all matters related to termination of an August 2003 license agreement covering Flamel’s Basulin Flamel will get a cash payment and a clear title to certain data from the relationship on the insulin formulation; the deal was ended in September 2004 (1/31) Genta Inc. (GNTA) Sanofi-Aventis Group (France) They formally terminated their deal to develop Genta’s cancer drug Genasense Sanofi provided notice of the termination in November 2004; there are no further financial obligations between them (5/10) BI ended an agreement on the HIV product MIV-310 (alovudine) The move followed a Phase II trial that did not meet targeted efficacy levels; Medivir is not planning further development (3/15) Medivir AB Boehringer (Sweden; SSE:MVIR) Ingelheim GmbH (Germany) 248 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Big Pharma Collaborations: Modified And Terminated Agreements (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Change from original agreement Terms/Details (Date) NeoPharm Inc. (NEOL) Akorn Inc. They ended a deal under which NeoPharm had access to manufacturing capacity at an Akorn facility The deal granting capacity to NeoPharm was signed in 2002; NeoPharm already made arrangements for its manufacturing needs (5/16) NitroMed Inc. (NTMD) Boston Scientific Corp. A research program on nitric oxide-enhancing technology came to a close Dec. 31 The technology was being studied with restenosis in balloon angioplasty; NitroMed intends to continue to explore using the technology in medical devices (12/29) Phytopharm plc (UK; LSE:PYM) Yamanouchi Pharmaceutical Co. Ltd. (Japan) Yamanouchi terminated deal covering Phytopharm’s Cogane, a product being developed for Alzheimer’s disease Yamanouchi’s license covered Japan and some other Asian countries (3/29) Schering exercised its right to terminate agreement covering Praecis’ Plenaxis product Schering cited the product not having received marketing authorization in Germany with a requisite label by June 30 as reason for ending the deal (9/28) Praecis Schering AG Pharmaceuticals (Germany) Inc. (PRCS) Notes: # The information in the chart does not cover agreements between biotech companies or agricultural agreements. * Private companies are indicated with an asterisk. Unless otherwise noted, stock symbols listed are on the Nasdaq market. AMEX = American Stock Exchange; ASX = Australian Stock Exchange; FSE = Frankfurt Stock Exchange; HSE = Helsinki Stock Exchange; LSE = London Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; PK = Pink Sheets; SSE = Stockholm Stock Exchange; SWX = Swiss Stock Exchange. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 249 2005 Manufacturing, Marketing And Distribution Agreements Between Biotechnology And Pharmaceutical Companies Biotech Co.* (Country; Symbol) Pharma Co. (Country) Product Terms/Details (Date) Adolor will co-promote GSK’s anti-thrombotic agent Arixtra in the U.S. Adolor is hiring a 30-person sales force and will receive undisclosed cost reimbursement for its promotional efforts (1/3) Alnylam Dowpharma Pharmaceuticals (unit of The Dow Inc. (ALNY) Chemical Co.) Deal for the manufacture and supply of Alnylam candidate RNAi therapeutics Dowpharma will manufacture siRNAs for use in clinical trials in age-related macular degeneration and respiratory syncytial virus infection (3/29) Ambion Inc.* Wyeth Deal to continue alliance for development and supply of cGMP-grade RNA that will be incorporated in Wyeth’s vaccine program Ambion division Ambion Diagnostics will manufacture RNA transcripts and supply the material for Phase I/II trials (3/8) Antisoma plc (UK; LSE:ASM) Raylo Chemicals (Canada) Deal for the manufacture of Antisoma’s AS141 1 (formerly AGRO100) The product is an anticancer aptamer; terms of the deal were not disclosed (3/14) Arexis AB* (Sweden) CMC Biopharmaceuticals (Denmark) Deal for the production of Arexis’ recombinant human BSSL product for upcoming clinical trials The bile salt-stimulated lipase will be tested for cystic fibrosis and preterm infants; terms of the deal were not disclosed (3/7) Biosignal Ltd. (Australia; ASX:BOS) Dr. Reddy’s Laboratories (India) Reddy’s Laboratories will develop a large-scale manufacturing procedure for Biosignal compounds The compounds are antibacterial furanones; terms of the deal were not disclosed (1/20) Cellegy PT Kalbe Farma Pharmaceuticals (Indonesia) Inc. (CLGY) PT Kalbe got rights to distribute Tostrex (testosterone gel) in parts of the Far East PT Kalbe got exclusive distribution rights in 1 1 countries, including Indonesia and Thailand; terms of the deal were not disclosed (3/9) Chromos Molecular Systems Inc. (Canada; TSE:CHR) AppTec Laboratory Services Inc. Alliance to provide a range of cell line engineering and contract manufacturing services They will coordinate marketing efforts under a nonexclusive arrangement; terms were not disclosed (2/16) Cytomedix Inc. (OTC BB:CYME) KOL Bio-Medical Instruments Inc. KOL will represent the company in certain East Coast areas The six-month deal relates to Cytomedix’s AutoloGel therapy; the commission-fee deal could be renewed (3/14) FIRST QUARTER Adolor Corp. (ADLR) 250 GlaxoSmithKline plc (UK) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology And Pharmaceutical Companies (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Product Terms/Details (Date) DOR BioPharma Inc. (AMEX:DOR) Cambrex Corp. Deal for process development and potential large-scale production of DOR’s RiVax ricin vaccine Cambrex will provide process development and cGMP production services for RiVax; terms were not disclosed (1/7) Evolutec Group plc* (UK) Cambrex Bio Science Baltimore Inc. Cambrex will manufacture Evolutec’s rEV131 for Phase III trials and marketing The product is in Phase II trials in allergic rhinitis and postoperative treatment following cataract surgery; terms were not disclosed (2/28) GeneExcel Inc.* ITX International Holdings Inc. ITX licensed liposome drug delivery technology for entrance into Japan markets ITX invested $700,000 in GeneExcel’s Series A financing; further terms were not disclosed (3/15) Gen-Probe Inc. (GPRO) F. Hoffmann-La Roche Ltd. (Switzerland) Gen-Probe will purchase products for use in molecular diagnostic assays for human papillomavirus Roche will manufacture DNA probes for HPV, which Gen-Probe will purchase at agreed-upon transfer prices (2/15) Helix BioMedix Inc. (OTC BB:HXBM) American Global Health Group LLC Deal for inclusion of Helix peptide technology in AGHG skin care products The products are being developed for the Asian market; Helix is entitled to royalties on any resulting sales (2/22) ICOS Corp. (ICOS) Solvay Pharmaceuticals Inc. Co-promotion agreement for AndroGel (testosterone gel), which is approved in the U.S. ICOS will provide promotional support through physician details and other activities and be paid a fee per detail, as well as fees based on specified sales goals (1/31) Nymox Pharmaceutical Corp. (NYMX) Alifax SpA (Italy) Deal for the marketing and sales of Nymox’s AlzheimAlert product in Italy Alifax will distribute the Alzheimer’s disease diagnostic in Italy under undisclosed terms (2/16) Pharming Group NV (the Netherlands; Euronext:PHARM) Diosynth BV (the Netherlands; unit of Akzo Nobel) Supply agreement for the production of Pharming’s recombinant human C1 inhibitor The product is being developed for hereditary angioedema; terms of the deal were not disclosed (2/8) Qiagen NV (the Netherlands; QGEN) Roche Molecular Systems Roche will market Qiagen’s media sample preparation kits under its AmpliLute trademark Terms of the deal were not disclosed (2/9) Repligen Corp. (RGEN) GE Healthcare They amended 1999 supply agreement covering the manufacture of GE’s recombinant Protein A The agreement was extended through 2010 and expanded to include an additional GE protein (2/8) Altana will co-promote Salix’s Xifaxan (rifaximin) Altana will promote the product for travelers’ diarrhea to the primary care physician market; terms were not disclosed (3/3) Salix Altana Pharma Pharmaceuticals U.S. Inc. Ltd. (SLXP) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 251 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology And Pharmaceutical Companies (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Savient O.R.C.A.Pharm Pharmaceuticals GmbH (Germany) Inc. (SVNT) Product Terms/Details (Date) Deal under which O.R.C.A. will market Soltamox (tamoxifen oral liquid solution) in Germany Savient subsidiary Rosemont Pharmaceuticals will manufacture the product and get payments based on sales (1/6) SECOND QUARTER Advancis Pharmaceutical Corp. (AVNC) Stada Arzneimittel AG (Germany) Stada will supply Amoxicillin Pulsys products for Advancis Stada subsidiary Clonmel Healthcare Ltd. will provide commercial supplies of the product, which is in Phase III trials for treating infections (4/19) Affymetrix Inc. (AFFX) CapitalBio Corp. (China) Deal to develop an advanced GeneChip-compatible personal scanner and a service provider program CapitalBio will offer the full line of Affymetrix GeneChip products under the deal; they intend to collaborate in other areas, as well (4/26) Allos Therapeutics Inc. (ALTH) Hovione (Portugal) Deal under which Hovione will manufacture Efaproxyn bulk drug substance The Phase III product is designed to sensitize hypoxic areas of tumors during radiation; the deal covers both pre- and postcommercialization needs (6/16) AlphaVax Inc.* Greer Laboratories AlphaVax assumed direct responsibility for vaccine manufacturing under a new lease agreement with Greer AlphaVax will use Greer’s vaccine production facility, and will employ several Greer staff who are involved in making AlphaVax vaccines; terms were not disclosed (6/23) Ambrx Inc.* CMC Biopharmaceuticals A/S (Denmark) Deal for the manufacture of an Ambrx pegylated recombinant growth hormone CMC will manufacture the product for use in human clinical studies; terms of the deal were not disclosed (6/3) Antisoma plc (UK; LSE:ASM) Heraeus GmbH (Germany) Heraeus will provide supplies of Antisoma’s AS1410 for clinical trials Trials of the telomere-targeting agent are expected to begin in 2006; terms of the deal were not disclosed (6/2) Ark Therapetuics Group plc (UK; LSE:AKT) BL&H Co. Ltd. (South Korea) BL&H got rights in South Korea to the wound-healing product Kerraboot Ark would get a double-digit royalty on sales in the covered territory (6/14) Avantogen Ltd. (Australia; ASX:ACU) Dr. Reddy’s Laboratories (India) Deal for the production of Avantogen’s GPI-100 adjuvant Dr. Reddy’s will manufacture the product under undisclosed terms (6/23) BioDiscovery Inc.* Tecan Schweiz AG (Switzerland) Collaboration to develop a data-management solution for interpreting microarray data They will integrate technologies in the deal, terms of which were not disclosed (6/29) 252 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology And Pharmaceutical Companies (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Product Terms/Details (Date) BioSante Undisclosed Pharmaceuticals U.S.-based company Inc. (AMEX:BPA) Deal for the manufacture of large-scale quantities of BioSante’s calcium phosphatebased nanotechnology The product will be tested by another company to develop an oral formulation of a marketed injectable protein product; terms were not disclosed (5/3) Cellectricon AB* (Sweden) Dipsi Industrie (France) Dipsi will distribute the Dynaflow System for ion channel drug discovery in France Dipsi will provide sales and technical support to the French market under undisclosed terms (5/17) Codexis Inc.* Shasun Chemicals and Drugs Ltd. (India) Manufacturing and supply agreement for a pharmaceutical intermediate for a generic drug Shasun will manufacture the compound, and Codexis will market it worldwide to the generic industry; Codexis will provide the biocatalyst for use in production, and they will share profits on sales (5/1 1) Co.don AG* (Germany) Bioengi Ltd. (Italy) Bioengi will market Co.don’s products for treating osteoarthritic knee joints and degenerated intervertebral discs The products are co.don chondrotransplant, co.don chondrosphere and co.don chondrotransplant DISC; terms of the deal were not disclosed (6/8) Combimatrix Group (CBMX) Inter Medical Co. Ltd. (Japan) Inter Medical will distribute CombiMatrix’s CustomArray microarray products in Japan Terms of the nonexclusive distribution deal were not disclosed (5/2) Corautus Genetics Inc. (VEGF) Boehringer Ingelheim Austria GmbH Deal covering manufacturing of VEGF-2 plasmid DNA for Phase III trials and future commercial use BI will manufacture Corautus’ product under undisclosed terms (5/16) Cortex Biochem Inc.* Bouty SpA (Italy) Bouty got rights to market Cortex’s MagaZorb Nucleic Acid Isolation Kits and associated reagents in Italy The exclusive distribution deal includes Bouty’s biotechnology division, Technogenetics Srl; terms of the deal were not disclosed (6/14) Exiqon A/S* (Denmark) Roche Diagnostics (Switzerland) Roche was named sole distributor of Exiqon’s ProbeLibrary Kits The kits are used for gene expression analysis and target validation of microarray experiments; terms were not disclosed (5/17) Generex Biotechnology Corp. (Canada; GNBT) MedGen Corp. (Lebanon) MedGen got marketing rights to the diabetes product Oral-lyn in Lebanon MedGen made an up-front license payment and is obligated to certain minimum purchases of the product from Generex (6/16) Gilead Sciences Inc. (GILD) Aspen Pharmacare (South Africa) Aspen will manufacture and distribute Gilead’s HIV products Truvada and Viread in Africa The nonexclusive deal includes the 95 resource-limited countries in Gilead’s global access program; Aspen also will be responsible for regulatory approvals (4/25) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 253 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology And Pharmaceutical Companies (Continued) Biotech Co.* (Country; Symbol) Product Terms/Details (Date) Iconix Rosetta Pharmaceuticals Biosoftware (unit Inc.* of Merck & Co. Inc.) Deal to establish interoperability between their systems The deal involves Rosetta’s Resolver system and Iconix’s DrugMatrix Informatics system; terms were not disclosed (6/20) ImmunoDesigned Molecules SA* (France) Cambridge Laboratories Ltd. (UK) CLL got marketing rights to Junovan (Mepact or L-MTP-PE), a Phase III cancer product, in the UK and Ireland IDM gets an up-front license fee and is entitled to milestone payments, as well as royalties on any resulting sales (6/21) InSite Vision Inc. (AMEX:ISV) Unnamed company They signed a deal for the long-term supply of azithromycin Azithromycin is the active drug in InSite’s AzaSite ocular anti-infective product, which is in Phase III trials (5/18) Iomai Corp.* The Dow Chemical Co. Iomai will use the Pfenex Expression Technology from Dowpharma to produce heat labile enterotoxin Iomai will use the technology to produce a component of its platform for the delivery of vaccines to the skin; terms were not disclosed (6/24) Large Scale Biology Corp. (LSBC) EMD Biosciences Inc. (unit of Merck KGaA) LSBC will manufacture and supply one of its protein products for distribution by EMD Terms of the multiyear agreement were not disclosed (4/28) Microbix Biosystems Inc. (Canada; TSE:MBX) Undisclosed vaccine producer They extended by 90 days a deal to evaluate Microbix’s technology to boost the production yield of flu vaccine The initial evaluation period was to expire June 30; terms of the deal were not disclosed (6/24) Morphotek Inc.* Baxter Healthcare Corp. They expanded existing deal to include manufacturing of Morphotek’s Phase I cancer antibody MORAb-003 Baxter already was manufacturing MORAb009 and MORAb-004; terms of the deal were not disclosed (6/30) Neurobiological Technologies Inc. (NTII) Nordmark Arzneimittel GmbH & Co KG (Germany) and Baxter Pharmaceutical Solutions LLC Deal for the manufacturing and packaging of NTI’s Viprinex (ancrod) for Phase III trials in acute ischemic stroke Nordmark will manufacture the biological active ingredient, and Bayer will fill and package the product; terms of the deal were not disclosed (6/27) Novavax Inc. (NVAX) Cardinal Health Inc. They restructured agreement for the manufacture of Novavax’s Estrasorb Novavax will manufacture the topical emulsion for estrogen therapy; Cardinal will take care of fill-finish operations; the move is expected to reduce Novavax’s manufacturing costs (5/9) OpGen Inc.* M&S Instruments Inc. (Japan) M&S got exclusive distribution rights to OpGen products in Japan M&S will provide researchers access to Optical Mapping, OpGen’s whole-genome analysis system, under undisclosed terms (4/28) 254 Pharma Co. (Country) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology And Pharmaceutical Companies (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Product Terms/Details (Date) Physiomics plc (UK; AIM:PYC) Bayer Technology Services GmbH (Germany) Physiomics will distribute Bayer’s PK-Sim pharmacokinetic modeling products and services Terms of the exclusive, renewable five-year deal were not disclosed (6/23) Proteome Agilent Systems Technologies (Australia; ASX:PXL) Inc. Collaboration to develop an integrated solution for the analysis of glycoproteins Proteome will make its GlycomIQ software platform compatible with Agilent’s ion trap mass spectrometers (4/18) Spectrum Cura Pharmaceuticals Pharmaceuticals Inc. (SPPI) Co. Inc. Deal under which Cura would market Spectrum’s carboplatin injection product Spectrum expects approval of the generic cancer product by mid-2005; terms of the deal were not disclosed (4/14) VaxGen Inc. (PK:VXGN) Bristol-Myers Squibb Co. VaxGen’s joint venture Celltrion will manufacture biologic products being developed by BMS Celltrion, in South Korea, was established by Vaxgen and three South Korean partners; terms of the deal were not disclosed (6/21) WITA GmbH* (Germany) SC Biosciences Corp. (Japan) SCBC will distribute WITA’s proteomics technologies in Japan Terms of the deal were not disclosed (4/27) THIRD QUARTER Agenix Inc. (Australia; ASX: AGX) Diosynth Biotechnology (unit of NV Organon) Diosynth will manufacture ThromboView for Phase III trials and commercial sale The product uses radiolabeled antibodies to locate blood clots in the body; terms of the deal were not disclosed (8/10) Alpha Innotech Corp.* GE Healthcare (UK) Alpha Innotech will develop a line of imaging systems for GE The products will be sold worldwide under the GE brand; terms of the deal were not disclosed (9/2) Ambion Inc.* GE Healthcare (UK) GE will manufacture microRNA microarrays for Ambion GE will use its CodeLink Bioarray technology in the license supply agreement; terms of the deal were not disclosed (9/29) Auxilium DPT Laboratories Pharmaceuticals Inc. (AUXL) They extended deal for the manufacturing of Testim through 2010 The deal for manufacturing Auxilium’s Testim was set to expire in 2005; DPT will manufacture it under undisclosed terms (9/21) Cephalon Inc. (CEPH) Deal to co-promote Attenace (modafinil), for which an sNDA has been filed with the FDA for treating attention deficit/ hyperactivity disorder Cephalon will pay McNeil commission fees on sales of Attenace in the deal, which will last up to three years (9/1) McNeil Consumer & Specialty Pharmaceuticals BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 255 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology And Pharmaceutical Companies (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Product Terms/Details (Date) CombiMatrix Group (CBMX) VWR International Inc. VWR will distribute CustomArrays and CatalogArrays for CombiMatrix Terms of the global distribution agreement were not disclosed (9/13) DOR BioPharma Inc. (AMEX:DOR) Dowpharma Dow will provide process development services for DOR’s oral botulinum vaccine, BT-VACC Dow will use its Pseudomonas-based Pfenex Expression Technology in the effort; terms of the deal were not disclosed (7/26) Enobia Pharma Inc.* (Canada) Laureate Pharma Inc. Deal for the process development and manufacture of Enobia’s recombinant enzyme sPHEX Metallo Peptidase Phase I trials are expected to start in 3Q:06; terms of the deal were not disclosed (9/21) ExonHit Therapeutics SA* (France) Agilent Technologies Inc. Agilent will distribute ExonHit’s SpliceArrays technology SpliceArrays is a new generation of microarrays to detect alternative splicing (9/1) GeneGo Inc.* Rosetta Biosoftware (unit of Merck & Co. Inc.) Deal to establish interoperability between Rosetta’s Resolver system and GeneGo’s MetaCore system Researchers will be able to exchange data between the systems for analyzing gene expression data and for pathway analysis; terms were not disclosed (7/18) Gene Logic Inc. (GLGC) GE Healthcare Deal under which GE will distribute Gene Logic’s Sciantis System worldwide The product is an an online gene expression analysis system; terms of the deal were not disclosed (7/19) IBEX Technologies Inc. (Canada; TSE:IBT) Seikagaku Corp. (Japan) and Prozyme Inc. Seikagaku and Prozyme will market IBEX enzymes to customers in the worldwide research community Terms of the deal with Prozyme and Seikagaku subsidiary Associates of Cape Cod Inc. were not disclosed (9/20) InSite Vision Inc. (AMEX:ISV) Cardinal Health Cardinal will manufacture commercial supplies of AzaSite (1% azithromycin) Cardinal has been manufacturing the antiinfective for clinical trials; terms were not disclosed (9/22) Lantibio Inc.* Apotex Fermentation Inc. (Canada) Apotex will supply and help in the development of Lantibio’s Moli1901 product The product is being developed for dry-eye syndrome and cystic fibrosis; Apotex is entitled to royalty payments (8/15) Mesoblast Ltd. Cambrex Corp. (Australia; ASX:MSB) Deal for large-scale production of Mesoblast’s adult stem cells Cambrex will produce clinical-grade cells under undisclosed terms (9/20) NeoPharm Inc. (NEOL) Diosynth Biotechnology (unit of NV Organon) They amended manufacturing deal covering NeoPharm’s IL13-PE38QQR Deal covers manufacturing following the ongoing Phase III trial in brain cancer if NeoPharm moves ahead with BLA filing (9/21) Osiris Therapeutics Inc.* JCR Pharmaceuticals Co. Ltd. (Japan) JCR got rights in Japan to sell stem cells for use in drug screening and evaluation The deal is an expansion of a license agreement under which JCR got rights to a stem cell drug for treating graft-vs.-host disease (8/4) 256 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology And Pharmaceutical Companies (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Product Terms/Details (Date) Peptech Ltd. Undisclosed (Australia; ASX:PEP) company Deal for the manufacturing of Peptech’s anti-TNF domain antibody The unnamed company will manufacture the antibody to GMP standards (9/12) QBI Life Sciences (unit of Quintessence Biosciences Inc.) Takara will distribute QBI’s tools for membrane proteins in Japan, China and Korea Terms of the deal were not disclosed (7/18) Takara Bio Inc. (Japan) Samaritan Norbrook Pharmaceuticals Laboratories S.R.O. Inc. (AMEX:LIV) (Northern Ireland) Norbrook would supply raw SP-01A is Samaritan’s lead HIV drug; its formulation material to manufacturing partner is Pharmaplaz Samaritan’s manufacturing (9/27) partner upon approval of SP-01A Vernalis plc (UK; LSE:VER) Deal for the process development, scale-up and manufacturing of Vernalis’ V10153 for Phase III trials Diosynth will manufacture the thrombolytic agent under undisclosed terms (9/22) Verus acquired exclusive, worldwide rights to the approved product Twinject Twinject is an epinephrine auto-injector indicated for the emergency treatment of severe allergic reactions (anaphylaxis); it also got rights to other technology and development programs (7/6) Diosynth Biotechnology (unit of NV Organon) Verus Hollister-Stier Pharmaceuticals Laboratories LLC Inc.* FOURTH QUARTER Acorda Therapeutics Inc.* Cardinal Health Two-year deal to expand the sales force for Acorda’s Zanaflex Capsules Cardinal will provide about 160 contract sales representatives to address the primary care market (1 1/10) Affibody AB* (Sweden) Funakoshi Co. Ltd. (Japan) Funakoshi will promote and distribute Affibody research reagents in Japan Terms of the deal were not disclosed (10/4) BioDelivery Sciences International Inc. (BDSI) Aveva Drug Delivery Systems Inc. Aveva will prepare supplies for Phase III trials and commercial manufacturing of BDSI’s BEMA Fentanyl The product is an oral adhesive disc formulation of the narcotic fentanyl; Aveva will exclusively manufacture and supply the discs (1 1/8) Bioxel Pharma Inc. (Canada; CDNX:BIP) Undisclosed European manufacturer Renewable two-year deal under which Bioxel will manufacture and supply paclitaxel Paclitaxel deliveries to the generic manufacturer are expected to generate sales of $1.5M to $2M per year for Bioxel (10/27) New Harbor got rights in China to a nitric oxide donor product for treating anal disorders NHC will work through PUMC Pharmaceuticals Co. Ltd. to bring products to market in China; Cellegy would get royalties on sales (1 1/22) Cellegy New Harbor Pharmaceuticals Corp. Inc. (CLGY) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 257 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology And Pharmaceutical Companies (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Product Terms/Details (Date) Codexis Inc.* Arch Pharmalabs Ltd. (India) Codexis will use its MolecularBreeding technology to manufacture an undisclosed compound for Arch Codexis is entitled to up-front and milestone payments from Arch, a generic pharmaceutical company (10/1 1) Codexis Inc.* Matrix Laboratories Ltd. (India) Deal to develop a process for the manufacture of an undisclosed drug Codexis is entitled to R&D funding, milestone payments and royalties; it will use its MolecularBreeding technology in the effort (10/1 1) Cortex Biochem Inc.* Vita Inc. (Japan) Vita will market Cortex products in Japan The deal covers the MagaZorb Nucleic Acid Isolation Kits and associated reagents, and magnetic separation and immunoreagent products (10/1 1) Cubist ACS Dobfar SpA Pharmaceuticals (Italy) Inc. (CBST) ACS was named the singlesource supplier of the active ingredient for Cubist’s antibiotic drug Cubicin ACS has been supplying the ingredient for clinical trials since 1998; it now will be the only supplier (1 1/30) Discovery Laboratories Inc. (DSCO) Laureate Pharma Inc. Discovery is purchasing Laureate’s manufacturing operations in Totowa, N.J. Laureate has been providing manufacturing services to Discovery for more than two years; Discovery is paying $16M in cash for the facility (12/28) GenTel BioSurfaces Inc.* Abnova Corp. (Taiwan) Deal to combine technologies to develop multiplex immunoassays Terms of the deal were not disclosed (1 1/9) Hemispherx Biopharma Inc. (AMEX:HEB) HollisterStier Laboratories They signed a letter of intent for the contract manufacturing of Hemispherx’s Ampligen Terms of the deal were not disclosed (10/10) ImmunoGen Inc. (IMGN) Diosynth Biotechnology (unit of NV Organon) Diosynth will manufacture ImmunoGen’s huN901 antibody The antibody will be used in ImmunoGen’s huN901-DM1 anticancer compound (10/6) Microbia Inc.* Ranbaxy Laboratories Ltd. (India) Deal to improve the biomanufacturing process for a Ranbaxy product Microbia is entitled to R&D funding and potential development milestone payments (1 1/1) ProBioGen AG* (Germany) SAFC Biosciences (unit of SigmaAldrich Group) Deal under which SAFC will market ProBioGen’s cell line engineering services The services cover development of hightiter cells for production of biotherapeutics; terms were not disclosed (1 1/1) Deal to study ProtoKinetix’s AAGP for the stabilization of the partner’s vaccines AAGP is a synthetic antifreeze glycoprotein; terms of the deal were not disclosed (10/6) ProtoKinetix Undisclosed Inc. (OTC BB:PKTX) company 258 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology And Pharmaceutical Companies (Continued) Biotech Co.* (Country; Symbol) Pharma Co. (Country) Product Terms/Details (Date) RxKinetix Inc.* Indian Immunologicals Ltd. (India) RxKinetix will work to develop improved formulations of a hepatitis B vaccine The vaccine will be formulated in RxKinetix’s ProJuvant delivery platform; terms of the deal were not disclosed (1 1/2) SciGen Ltd. (Singapore; ASX:SIE) Bioton (Poland) and Hefei Life Science & Technolology Investments and Development (China) They established a joint venture to manufacture biopharmaceuticals in China Among the drugs to be produced there will be SciGen’s insulin and hepatitis B products; Hefei has a deal with SciGen to distribute SciGen products in China (12/13) TolerRx Inc.* Abbott Laboratories Deal under which Abbott will manufacture TolerRx’s TRX4 monoclonal antibody Abbott will supply the product for clinical trials and potential commercial launch; terms were not disclosed (1 1/29) TopoTarget A/S (Denmark; CSE:TOPO) Undisclosed company The unnamed company will promote TopoTarget’s Savene in Austria and four Eastern European countries The drug is being developed for treating accidental extravasations of anthracycline drugs; launch is anticipated late in 2006 (12/22) Viragen Inc. (AMEX:VRA) Kuhnil Pharm Co. Ltd. (South Korea) Kuhnil got rights to distribute Multiferon in South Korea Viragen gets an up-front fee; Kuhnil gets exclusive rights for 10 years; further terms were not disclosed (12/6) ViroPharma Inc. (VPHM) Eli Lilly and Co. Amended manufacturing deal calls for Lilly to increase its supply of Vancocin ViroPharma, expecting a possible increase in demand for the Clostridium difficile infection product, will pay Lilly up to $4.5M more than provided for in the original contract through early 2006 (1 1/3) Notes: # The information in the chart does not cover agricultural agreements or those between biotech companies. * Private companies are indicated with an asterisk. AIM = Alternative Investment Market; AMEX = American Stock Exchange; ASX = Australian Stock Exchange; CDNX = Canadian Venture Exchange; CSE = Copenhagen Stock Exchange; LSE = London Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; PK = Pink Sheets; TSE = Toronto Stock Exchange. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 259 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Genentech exercised its option to extend for three years a licensing agreement for antibody-generation technology Genentech purchased Abgenix stock and would pay milestone and royalty fees as products advance; the deal covering XenoMouse technology originally was signed in 1999 (3/14) Acadia Sepracor Inc. Pharmaceuticals (SEPR) Inc. (ACAD) They will jointly research and develop agonists and antagonists of selective muscarinic receptors for CNS disorders, including Acadia’s m1 agonist program Sepracor is buying $10M of Acadia stock at a 40% premium, and will buy up to $10M more in stock at a 25% premium in one year; Acadia also will get research funding for three years; a single approval would result in $40M of payments to Acadia, plus royalties on sales (1/1 1) ActiveSight* (unit of Rigaku/ MSC) Serenex Inc.* Deal for the co-crystallization of Serenex molecules with proteins expressed by ActiveSight Additional details of the deal were not disclosed (2/23) AdnaGen AG* (Germany) Gen-Probe Inc. (GPRO) Gen-Probe licensed technology for detecting rare, circulating tumor cells that are an early event in metastasis Gen-Probe gets exclusive access for molecular diagnostic tests for prostate and bladder cancers; AdnaGen gets $1.75M in license fees, up to $2.25M in milestones and royalties on any resulting sales (1/3) Aerogen Inc. (AEGN) Biota Holdings Ltd. (Australia; ASX:BTA) Deal to develop Biota’s CS-8958, a long-acting neuraminidase inhibitor, with Aerogen’s Aeroneb nebulizer Work on the influenza product is being funded under a $5.6M grant to Biota from the National Institutes of Health; terms were not disclosed (3/9) AEterna Zentaris Inc. (Canada; AEZS) Keryx Biopharmaceuticals Inc. (KERX) Keryx got certain rights to develop and sell ErPC in North America, South Africa, Israel, Australia and New Zealand The product, designed to block PI3K-AKT pathways, is an analogue of perifosine, for which Keryx already had North American rights; terms were not disclosed (1/6) Agencourt Bioscience Corp.* Dyadic International Inc. (OTC BB:DYAD) Agencourt will sequence the genome of Dyadic’s fungus, Chrysosporium lucknowense, also known as C1 The information will be used for potential new protein and enzyme products; terms of the deal were not disclosed (2/17) FIRST QUARTER Abgenix Inc. (ABGX) 260 Genentech Inc. (NYSE:DNA) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Alnylam GeneCare Pharmaceuticals Research Inc. (ALNY) Institute Co. Ltd. (Japan) GeneCare got an exclusive license to develop RNAi therapeutics against two DNA helicase genes associated with cancer Alnylam gets up-front and annual payments, as well as potential milestones and royalties; it also kept the right to negotiate co-development and -promotion deals on the products in the U.S. (1/6) Altair Nanotechnologies Inc. (ALTI) Spectrum acquired worldwide rights to RenaZorb (two secondgeneration lanthanum-based phosphate binding agents) Spectrum will make an up-front payment of 100,000 shares of restricted stock and make a $200,000 equity investment; Altair also is eligible to receive milestone and royalty payments (1/31) Angiotech CABG Medical Pharmaceuticals Inc. (CABG) Inc. (Canada; ANPI) CABG got a license to paclitaxel technology for treating restenosis and proliferative disease Angiotech gets a warrant to purchase 1.26M CABG shares, exercisable at $0.0 1, and potential milestone and royalty payments; also, Angiotech will purchase up to $10M in CABG stock at a 15% premium (3/23) Antigenics Inc. (AGEN) Pharmexa A/S (Denmark; CSE: PHARMX) Pharmexa licensed an adjuvant for use with its HER-2 Protein AutoVac pharmaccine Pharmexa will formulate the pharmaccine with the QS-21 adjuvant; terms of the deal were not disclosed (1/18) Ardais Corp.* Cytomyx Holdings plc* (UK) Cytomyx is acquiring Ardais’ biorepository of more than 130,000 clinically annotated biospecimens Cytomyx also will acquire the lab facilities and equipment and will hire Ardais’ biological operations personnel; terms were not disclosed (3/30) Atugen AG* (Germany) Asinex Ltd.* (Russia) Collaboration to discover and develop cancer drugs targeting the kinase PKN3 They will work on the program on a sharedrisk basis; any revenues would be equally divided (2/7) Avidex Ltd.* (UK) Active Biotech AB (Sweden; SSE:ACTI) Active will use Avidex’s monoclonal T-cell receptor technology to help develop the cancer product Anyara Avidex’s mTCR product will be used for characterization of the drug during clinical development; terms were not disclosed (3/7) BCY LifeSciences Inc. (Canada; TSE:BSY) Align Pharmaceuticals Inc.* Align will further develop and market BCY’s DCF 987, a Phase II product for respiratory conditions BCY is entitled to up-front, milestone and royalty payments; the product is the first in Align’s portfolio (2/25) Benitec Ltd. GenOway SA* (Australia; ASX:BLT) (France) GenOway got rights to develop transgenic animals using DNA-directed RNA interference Benitec gets an up-front license fee and ongoing royalties under the worldwide, nonexclusive deal (3/22) BioFocus plc (UK; AIM:BIO) Deal to accelerate lead discovery of Senexis drugs for Alzheimer’s disease Terms of the deal were not disclosed (3/7) Spectrum Pharmaceuticals Inc. (SPPI) Senexis Ltd.* (UK) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 261 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) BioKine Therapeutics Ltd.* (Israel) BioTie Therapies Corp. (Finland; HEX:BTH1V) BioTie gained exclusive rights to develop the antiinflammatory small-molecule compound BKT104 BioKine is entitled to receive milestone payments in the deal, along with royalties on any resulting sales (1/12) Biolex Inc.* Medarex Inc. (MEDX) Biolex will create a commercial line for an undisclosed Medarex monoclonal antibody At Medarex’s option, Biolex may scale-up and manufacture the antibody following commercial-line creation; terms were not disclosed (2/4) Biovation Ltd.* (UK) Scancell Ltd.* (UK) Biovation will apply its DeImmunisation technology to up to two further Scancell antibodies, including SC101 The goal is to help prepare the antibodies for clinical trials; terms of the deal were not disclosed (1/1 1) Caliper Life Sciences Inc. (CALP) Predicant Biosciences Inc.* Predicant got nonexclusive access to microfluidics technology for analyzing proteins using mass spectrometry Predicant is developing proteomic tests; terms of the deal were not disclosed (1/6) Caprion ICOS Corp. Pharmaceuticals (ICOS) Inc.* Collaboration for the joint development of therapeutic antibodies for treating cancer Caprion gets an up-front payment and license fees; the deal includes reciprocal milestone and royalty payments; also, ICOS has an option to co-develop and co-promote certain products (3/31) Celgene Corp. (CELG) EntreMed Inc. (ENMD) EntreMed licensed rights to Celgene’s small-molecule tubulin inhibitor compounds for the treatment of cancer Celgene gets an up-front licensing fee and potential milestone payments under the worldwide, exclusive deal (3/24) Celladon Corp.* Targeted Genetics Corp. (TGEN) Collaboration to develop adeno-associated virus-based gene therapies for treating congestive heart failure Targeted Genetics committed $2M toward development of AAV vectors containing the SERCA2a gene and phospholamban gene mutations, and is eligible to receive milestone and royalty payments (1/4) Cell Therapeutics Inc. (CTIC) DiaKine Therapeutics Inc.* DiaKine licensed the small molecule Lisofylline for development in diabetes and related complications CTI gets a license fee, potential milestone and royalty payments, and an equity interest in DiaKine; CTI retains all rights in nondiabetes applications (1/4) Chicago Labs Inc.* Spectrum Pharmaceuticals Inc. (SPPI) Spectrum acquired an exclusive license to endothelin B agonists for the treatment of cancer Chicago Labs, which licensed the technology from the University of Illinois, gets $100,000 up front, along with potential milestone and royalty payments (2/18) 262 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) CombiMatrix Group (CBMX) Benitec Ltd. (Australia; ASX:BLT) Benitec got a nonexclusive license to use pools of siRNAs against viral diseases, and a coexclusive sublicense to two sequences targeting HIV genes In return, CombiMatrix got a nonexclusive license to patents for the development of RNAi therapeutics against diseases resulting from biological, chemical, radioactive and other weapons; the companies also will collaborate in other areas (2/22) ComGenex Inc.* (Hungary) Echelon Biosciences Inc.* (subsidiary of AEterna Zentaris Inc.) They finalized deal to transfer to Echelon all rights to technology created in their collaboration The rights are to develop, manufacture and market certain PI3K inhibitors for cancer indications; terms of the deal were not disclosed (2/1) Control Delivery Systems Inc.* Alimera Inc.* Collaboration to develop and market a treatment for diabetic macular edema Alimera also has an option to develop three additional products using CDS’s delivery technology; terms were not disclosed (2/16) Corixa Corp. (CRXA) Lorantis Ltd.* (UK) Deal to continue development of a hepatitis B vaccine containing Corixa’s RC-529 adjuvant and Lorantis’ CV-1831, a hepatitis B core antigen The antigen previously was owned by Apovia Inc.; Lorantis acquired Apovia’s interest in the technology and will assume many of Apovia’s responsibilities under the deal with Corixa; Lorantis and Corixa will share costs and revenues (3/3) Corixa Corp. (CRXA) Genentech Inc. (NYSE:DNA) Genentech got exclusive rights to an undisclosed target for development of humanized antibody-based therapeutics Corixa gets a $1.6M up-front license fee and up to $8.25M in milestone payments, as well as royalties on any sales (1/13) Cresset BioMolecular Discovery Ltd.* (UK) Pharmagene plc (UK; LSE: PGN) Cresset will attempt to find novel leads against a Pharmagene discovery target Terms of the deal were not disclosed (3/2) Crucell NV (the Netherlands; CRXL) Vascular Biogenics Ltd.* (Israel) Vascular Biogenics got rights to use the PER.C6 cell line in gene therapeutics based on adenoviral vectors Crucell gets a research license payment and annual license fees in the nonexclusive deal (3/30) Crucell NV (the Netherlands; CRXL) SingVax Pte. Ltd. (Singapore) SingVax got rights to PER.C6 technology for use in vaccines against Japanese encephalitis Crucell gets up-front, annual and potential milestone payments, as well as royalties on any sales and a preferred position to negotiate marketing rights outside the AsiaPacific region (3/22) Crucell NV (the Netherlands; CRXL) Genentech Inc. (NYSE:DNA) Genentech is evaluating Crucell’s STAR technology for the production of antibodies and other proteins Genentech is funding the joint evaluation program, and has an option to sign a nonexclusive license agreement (1/7) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 263 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Curis Inc. (CRIS) Genentech Inc. (NYSE:DNA) Curis exercised its U.S. co-development option to develop a product for topically treating basal cell carcinoma Curis now will share in costs and profits for the preclinical compound from their 2003 collaboration based on inhibition of the Hedgehog signaling pathway (2/1) Cyntellect Inc.* Undisclosed company The company will access Cyntellect’s Cell Xpress service Terms of the deal were not disclosed (1/27) Demegen Inc.* Pacgen Biopharmaceuticals Corp.* (Canada) Pacgen got a license to certain peptides for treating oral diseases Pacgen’s initial focus will be on a treatment for oral candidiasis; terms of the deal were not disclosed (3/22) Dharmacon Inc.* Genentech Inc. (NYSE:DNA) Genentech will use Dharmacon RNAi technology for drug discovery and development Dharmacon will supply Genentech a range of siRNA reagents under undisclosed terms (1/21) Directif GmbH (Germany; subsidiary of November AG*) Epidauros Biotechnologie AG* (Germany) They formed a joint venture to develop applications for Directif’s LabChip technology in personalized medicine They are pooling know-how to develop applications for drug development; terms were not disclosed (3/23) Discovery Partners International Inc. (DPII) Chroma Therapeutics Ltd.* (UK) DPI will use its compound collection and other technologies to identify compounds for Chroma targets Terms of the deal were not disclosed (3/29) Domantis Ltd.* (UK) Tanox Inc. (TNOX) Domantis will use its Domain Antibodies technology to discover therapeutic product leads for Tanox Domantis gets an up-front fee, research funding and annual fees, as well as potential milestone and royalty payments; the focus is autoimmune diseases (3/22) Durect Corp. (DRRX) Endo Pharmaceuticals Inc. (ENDP) Endo got exclusive rights to Durect’s sufentanil-containing transdermal patch in the U.S. and Canada Durect gets $10M up front and up to $35M in regulatory and commercial milestones, as well as royalties on any sales of the pain product; Endo assumed development responsibilities (3/14) EndoChem Inc.* QuatRx Pharmaceuticals Co.* QuatRx acquired rights to QRX-431, an orally active compound for the treatment of lipid disorders and obesity Terms of the exclusive worldwide deal were not disclosed (3/15) Epitomics Inc.* InNexus Biotechnology Inc. (Canada; VSE:IXS) Deal to develop antibodies for certain targets that will be modified for delivery using InNexus’ TransMab technology Epitomics will supply the antibodies; they plan to develop products through Phase II before licensing them out; financial details were not disclosed (1/12) 264 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Evotec OAI AG (Germany; FSE:EVT) AnorMed Inc. (Canada; TSE:AOM) Evotec will support chemical development of AnorMED candidate AMD 3100 Evotec will complete the full validation of the process for the Phase III product under undisclosed terms (2/16) Galmed International Ltd.* (Malta) BioLineRx Ltd.* (Israel) BioLineRx licensed worldwide rights to BL-1060, a small molecule for treating fatty liver disease Terms of the exclusive deal on the preclinical product were not disclosed (3/14) GenData Research Corp.* Amgen Inc. (AMGN) Amgen will sponsor research for discovery and development of therapeutics and diagnostics for an undisclosed disorder Amgen will select genetic targets identified by GenData’s population genetics discovery platform; specific terms were not disclosed (1/5) GeneGo Inc.* RNA Co. Ltd.* (Japan) RNA Co. licensed GeneGo’s MetaCore technology for use in RNAi drug discovery Terms of the deal were not disclosed (1/24) Generation Biotech LLC* Qiagen NV (the Netherlands; QGEN) Qiagen licensed a technology for haplotypespecific extraction of DNA Qiagen subsidiary GenoVision Inc. got exclusive rights to the technology in all applications; terms were not disclosed (2/14) GlobeImmune Inc.* MycoLogics Inc.* MycoLogics gained rights to develop certain antifungal products under the GlobeImmune Tarmogen Technology MycoLogics plans to begin preclinical testing of human and animal vaccines targeting fungal diseases; terms of the deal were not disclosed (1/17) Helix Lumera Corp. BioPharma Corp. (LMRA) (Canada; TSE:HBP) Lumera exclusively licensed Helix’s Biochip technology for developing protein chip sets Helix is entitled to up-front, milestone and royalty payments, and retains the right to use the technology in its research (1/25) HMGene Inc.* WellGen Inc.* HMGene will screen WellGen compounds against its panel of genes involved in adipocyte development Terms of the research contract and licensing deal were not disclosed; WellGen would commercialize any resulting products (2/10) HTS Biosystems Inc.* Biacore International AB (Sweden; SSE:BCOR) Biacore acquired the FLEXChip System and related assets from HTS Biacore is paying $4M for the technology used in protein-interaction analysis (3/10) Iceland Genomics Corp.* (Iceland) Sequenom Inc. (SQNM) Deal to analyze Sequenom genetic markers associated with breast and prostate cancer in Icelandic patient samples Sequenom has commercialization rights for any resulting products, while Iceland Genomics is entitled to receive royalties on any sales (2/9) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 265 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) IGI Inc. (AMEX:IG) Senetek plc (OTC BB:SNTKY) Deal to evaluate IGI’s Novasome and micellar nanoparticle technologies for topical delivery of Senetek’s Invicorp erectile dysfunction therapy The deal was disclosed at the same time as Sentek’s offer to merge with IGI in a 50-50 deal; terms of the collaboration were not disclosed (1/14) ImClone Systems Inc. (IMCL) Genentech Inc. (NYSE:DNA) ImClone licensed rights to patents covering aspects of antibody technology The licenses relate to the EGFR-targeted antibodies Erbitux and IMC-1 1F8; terms were not disclosed (1/25) Incyte Corp. (INCY) Biosite Inc. (BSTE) Biosite exercised a semiexclusive research and diagnostics license and got an exclusive option to license 50 other diagnostic targets Incyte has received up-front fees and could receive additional milestones and royalties should Biosite develop and commercialize diagnostic products using any of the targets (2/7) IriSys Inc.* Avanir Pharmaceuticals Inc. (AMEX:AVN) Avanir acquired additional rights to its late-stage CNS product Neurodex Avanir licensed the product from IriSys in 2000; it has no further obligation to IriSys after paying $1.925M in cash and 2M shares of stock; Avanir still has royalty and other obligations to the discoverer, The Center for Neurologic Study (3/9) Isis OncoGenex Pharmaceuticals Technologies Inc. (ISIS) Inc.* They broadened collaboration to allow for development of two additional second-generation antisense cancer drugs Isis gets an up-front fee along with potential milestone and royalty payments; two drugs already are being developed under the deal that started in 2001 (3/16) Isis Sarissa Inc.* Pharmaceuticals (Canada) Inc. (ISIS) Sarissa licensed an antisense inhibitor of thymidylate synthase, which has applications in cancer Isis gets a $1M up-front fee in stock and potential milestone and royalty payments; Sarissa gets exclusive, worldwide rights (2/14) Large Scale Biology Corp. (LSBC) Icon Genetics AG* (Germany) Deal to combine technologies to develop an undisclosed product They will pool their plant-based platforms in an attempt to develop the difficult-toproduce drug; terms were not disclosed (3/1) MacroMed Inc.* Diatos SA* (France) Diatos got exclusive rights to develop and sell OncoGel (injectable paclitaxel) worldwide except North America and Korea They will collaborate on clinical development; MacroMed gets a license fee and potential milestone and royalty payments and retained the right to supply the product (1/5) MethylGene Inc. (Canada; TSE:MYG) EnVivo Pharmaceuticals Inc.* Collaboration to develop small-molecule HDAC inhibitors for treating neurodegenerative disorders MethylGene, which will contribute chemistry expertise, gets $1.1M the first year; then they will share costs and revenues equally (2/8) 266 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) NascaCell IP Discovery GmbH* (Germany) Partners International Inc. (DPII) Deal to jointly provide aptamer-based drug discovery services to the life sciences industry The effort combines NascaCell’s expertise in aptamers with DPI’s drug discovery capabilities; terms were not disclosed (3/21) Nektar Therapeutics (NKTR) Collaboration to develop an inhalable powder form of Zelos’ parathyroid hormone analogue Ostabolin-C Nektar will develop the dry-powder drug and inhalation system and get R&D funding along with potential milestone and royalty payments (1/24) Neuren Metabolic Pharmaceuticals Pharmaceuticals Ltd.* (Australia) Ltd. (Australia; ASX:MBP) Deal to co-develop Neuren’s neuroregenerative peptides for treating degenerative conditions They will jointly develop the technology and equally share all intellectual property and commercial outcomes (3/4) OctoPlus Technologies BV* (the Netherlands) Biolex Inc.* Collaboration to co-develop a controlled-release formulation of recombinant human alfa interferon They will combine OctoPlus’ biodegradable PolyActiv drug-delivery technology with Biolex’s BLX-883; terms of the deal were not disclosed (2/16) OriGene Technologies Inc.* Novasite Pharmaceuticals Inc.* Novasite licensed access to OriGene’s TruClone collection of full-length human cDNAs Terms of the deal were not disclosed (2/15) OsteoScreen Inc.* Neosil Inc.* Neosil licensed several hair-growth products from OsteoScreen Terms of the deal were not disclosed (2/16) Oxford BioMedica plc (UK; LSE:OXB) Biogen Idec Inc. (BIIB) Biogen got rights to use Oxford’s LentiVector technology in research activities Oxford gets an up-front license fee and annual maintenance payments; further terms were not disclosed (1/5) Pathway Diagnostics Corp.* Nanogen Inc. (NGEN) Deal under which Nanogen Terms of the nonexclusive, worldwide will develop diagnostics license agreement were not disclosed that detect genetic variations (3/22) associated with responses to depression and psychosis drugs Pharmacopeia Drug Discovery Inc. (PCOP) CV Therapeutics Inc. (CVTX) Drug discovery deal under which Pharmacopeia will provide discovery technologies Pharmacopeia gets research funding in addition to potential milestone and royalty payments (3/23) PharmaForm LLC* Auxilium Pharmaceuticals Inc. (AUXL) Auxilium got exclusive rights to develop and sell eight analgesic compounds using a transmucosal film technology The products will target acute and chronic pain; terms of the deal were not disclosed (2/8) Zelos Therapeutics Inc.* BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 267 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Pintex Vernalis plc Pharmaceuticals (UK; VNLS) Inc.* Vernalis acquired rights and other assets related to the oncology target Pin1 Pintex gets an initial cash payment and would get up to 1.5M Vernalis shares should a drug candidate enter human trials, which is not expected before 2008; Pintex would get another payment, bringing the total to $6.5M, upon product approval (3/31) ProMetic Life Sciences Inc. (Canada; TSE:PLI) Octapharma AG* (Switzerland) Octapharma gained access to ProMetic’s Mimetic Ligand affinity technology for the manufacture of protein drugs The deal was valued at C$1.4M to ProMetic (1/5) Protein Polymer Technologies Inc. (OTC BB:PPTI) Genencor International Inc. (GCOR) They expanded 2000 deal to include personal care product applications Genencor already had rights to industrial applications of PPTI’s polymer technology; PPTI gets an up-front and annual payments, as well as royalties on any sales (3/30) ProteoCell Biotechnologies Inc.* (Canada) Viropro Inc. (Canada; OTC BB:VPRO) Deal to commercialize recombinant biogeneric therapeutics for international markets They intend to evaluate and scale up certain biotherapeutic proteins, then transfer candidates to international clients for local commercial manufacturing (3/15) Revaax Rexahn Corp.* Pharmaceuticals* Rexahn licensed technology similar to antibiotics with activity against central nervous system activity The lead compound, RX-10,100, is expected to enter clinical trials within a year; terms of the deal were not disclosed (3/3) Rimonyx BioLineRx Ltd.* Pharmaceuticals (Israel) Ltd.* (Israel) BioLineRx got exclusive worldwide rights to develop BL-1030 BL-1030 is an L-selectin inhibitor targeted at inflammatory bowel disease; terms of the deal were not disclosed (1/13) Scynexis Inc.* Adherex Technologies Inc. (AMEX:ADH) Scynexis will provide medicinal and analytical chemistry services to Adherex The work will focus on Adherex’s smallmolecule cadherin antagonist development programs; terms were not disclosed (3/23) Seattle Genetics Inc. (SGEN) CuraGen Corp. (CRGN) CuraGen exercised its option to designate a second antigen target under their existing antibody-drug conjugate collaboration The option, stemming from their June 2004 collaboration, triggered a $1M payment to Seattle Genetics (2/15) Serologicals Corp. (SERO) OncoMethylome Sciences SA* (Belgium) OMS licensed fluorescent detection technology for development of diagnostic assays for detecting DNA methylation patterns OMS made the deal on the Amplifluor technology with Serologicals subsidiary Chemicon International Inc.; terms of the deal were not disclosed (3/30) 268 Company* (Country; Symbol) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Sunol Molecular Corp.* Tanox Inc. (TNOX) Tanox is acquiring Sunol’s tissue factor antagonist program for treating inflammatory diseases and cancer Tanox will issue 800,000 shares of common stock, which were valued at $8.26M, and pay $6 million to Sunol in the deal; Tanox also got nonexclusive rights to certain technologies for protein and antibody expression (3/28) Syntonix Serono SA Pharmaceuticals (Switzerland; Inc.* NYSE:SRA) Serono licensed exclusive rights to Transceptor and Synfusion technologies for developing interferon-beta:Fc products Serono intends to develop an inhaled interferon-beta therapy for multiple sclerosis; Syntonix gets an up-front license fee and is eligible for development milestones and sales royalties (3/31) Targeted Genetics Corp. (TGEN) Sirna Therapeutics Inc. (RNAI) Collaboration using TGEN’s adeno-associated virus delivery platform to develop drugs for Huntington’s disease The AAV platform will be combined with Sirna’s HD program and expertise in RNA silencing technologies; costs and any revenues will be shared (1/1 1) Tripos Inc. (TRPS) BioTie Therapies Corp. (Finland; HEX:BTH1V) Tripos will identify and optimize backup series for one of BioTie’s drug discovery programs Tripos, using its LeadHopping technology, also will create compound libraries; terms of the multiyear deal were not disclosed (2/7) VASTox plc (UK; AIM:VOX) Undisclosed company VASTox will target drugs to specific organs and cell types through the use of sugars VASTox will perform the work under a nine-month fee-for-service deal with the unnamed European company (2/23) Vertex Avalon Pharmaceuticals Pharmaceuticals Inc. (VRTX) Inc.* Avalon gained exclusive rights to develop and sell VX-944, a Phase I IMPDH inhibitor, for treating various cancers Vertex will get up to $73M in up-front and milestone payments, and royalties on any sales; Vertex also has certain co-promotion rights in the U.S. and Europe (2/15) ViaCell Inc. (VIAC) Genzyme Corp. (GENZ) Collaboration related to use of islet stem cells for treating diabetes The companies will conduct preclinical research in the area; terms of the deal were not disclosed (3/15) Xenova Group plc (UK; XNVA) Oxxon Therapeutics Inc.* Oxxon got rights to use Xenova’s DISC-HSV Vector in various indications in oncology and infectious diseases The deal is worth up to $83M to Xenova in up-front and milestone payments, in addition to royalties on any sales; Oxxon also could get additional rights for additional payments; Xenova keeps rights for the prophylaxis of herpes virus diseases (1/13) Cambridge Biostability licensed rights to Acambis’ enterotoxigenic E. coli vaccine against travelers’ diarrhea Acambis retained an option for an exclusive license to market the vaccine, HolaVaxETEC, in North America; terms of the deal were not disclosed (5/10) SECOND QUARTER Acambis plc (UK; ACAM) Cambridge Biostability Ltd.* (UK) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 269 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Access Hunter-Fleming Pharmaceuticals Ltd.* (UK) Inc. (AMEX:AKC) Collaboration for the oral delivery of a drug candidate for Alzheimer’s disease They will combine Access’s vitamin B-12 oral delivery technology with Hunter-Fleming’s Oligotropin (HF0420); terms of the deal were not disclosed (5/12) ActiveSight* Lexicon Pharmaceuticals Inc. (LEXG) ActiveSight will perform crystallography services for Lexicon The deal extends the co-crystallography of Lexicon’s small-molecule compounds to a second drug-target protein validated by Lexicon and expressed by ActiveSight; terms were not disclosed (4/27) Aegis Therapeutics LLC* Intranasal Technology Inc.* Expanded a deal to apply Aegis’ Intravail delivery technology to intranasal heparin and beta-interferon Terms of the deal were not disclosed (6/20) Affitech A/S* (Norway) Undisclosed UKbased company The unnamed company gets rights to use the Protein L gene as well as vectors and know-how of Protein L production The nonexclusive license covers use with research and preclinical development; terms of the deal were not disclosed (5/31) AlgoNomics NV* (Belgium) Genmab A/S (Denmark; CSE:GEN) Genmab got rights to access AlgoNomics’ Epibase platform for T-cell epitope identification Genmab will use the technology in validation of antibody leads; terms of the threeyear deal were not disclosed (5/12) Alkermes Inc. (ALKS) Cephalon Inc. (CEPH) Agreement for the commercialization of Vivitrex; Alkermes filed an NDA for the alcoholdependence drug in March Alkermes gets $160M in cash up front; it would get $1 10M more upon FDA approval and could get up to another $220M in sales-based milestones; they would share profits on a 50-50 basis (6/24) Alnylam Ambion Inc.* Pharmaceuticals Inc. (ALNY) Ambion got rights to provide research products and services under Alnylam’s KreutzerLimmer patent family The patents cover short interfering RNAs and their use to mediate RNAi in mammalian cells; terms of the nonexclusive license were not disclosed (6/8) Alnylam Benitec Ltd. Pharmaceuticals (Australia; ASX:BLT) Inc. (ALNY) Benitec and its licensees got an option to nonexclusively license Alnylam-controlled IP in the field of expressed RNA interference Alnylam would receive license fees and be entitled to milestone royalty payments on covered products; it also got reciprocal options on Benitec IP for expressed RNAi and synthetic siRNAs (4/12) Ambion Inc.* Cepheid got nonexclusive rights to incorporate Armored RNA technology in its in vitro molecular diagnostic products The Ambion Diagnostics division will manufacture custom reagents for Cepheid; terms of the deal were not disclosed (4/1 1) 270 Company* (Country; Symbol) Cepheid Inc. (CEPH) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Amrad Corp. Ltd. (Australia; ASX:AML) Serologicals Corp. (SERO) Serologicals subsidiary Chemicon International got additional rights to develop embryonic stem cell products into more kits and products The expanded deal also included the Walter Eliza Hall Institute of Medical Research; the initial 1999 license covering leukemia inhibitory factor now includes non-therapeutic uses; terms were not disclosed (4/5) AnalytiCon Bionaut Discovery Pharmaceuticals GmbH* (Germany) Inc.* Collaboration to identify anticancer compounds that inhibit the ability of tumor cells to survive stress conditions Bionaut will provide and validate compounds that have shown activity; AnalytiCon will optimize them for further preclinical development by Bionaut; terms of the deal were not disclosed (4/14) Angiotech Histogenics Pharmaceuticals Corp.* Inc. (Canada; ANPI) Histogenics got rights to use the biomaterial ChondroGEL in cartilage, ligament, meniscus and/or tendon repair Angiotech gets warrants to purchase Histogenics shares and would share any resulting revenue; it also retains all drugloaded rights to ChondroGEL (6/2) Angiotech Broncus Pharmaceuticals Technologies Inc. (Canada; ANPI) Inc.* Broncus got rights to use Angiotech’s Paclitaxel technology with its Exhale system for treating emphysema Angiotech gets warrants to purchase Broncus preferred stock and would get royalties on sales of resulting products (6/2) Array BioPharma Inc. (ARRY) Genentech Inc. (NYSE:DNA) They expanded collaboration to develop small-molecule drugs against an additional protein target in oncology Array gets additional research funding, as well as potential milestone and royalty payments; the January 2004 deal covered two Array oncology programs; Genentech has rights to resulting products (4/7) Asinex Ltd.* (Russia) Galapagos NV (Belgium; Euronext:GLPG) Collaboration to optimize leads for Galapagos’ validated bone and joint disease drug targets Asinex will use its computational chemistry and compound libraries to generate new leads; then they will design and optimize the lead structures; terms were not disclosed (5/12) Atugen AG* (Germany) Xantos Biomedicine AG* (Germany) Atugen will use its siRNA technology to validate a Xantos angiogenic compound in animal studies Terms of the deal were not disclosed (4/15) Collaboration to discover and develop small-molecule drugs in the area of inflammatory disease Avalon will identify lead compounds; MedImmune has all other responsibilities; Avalon gets an up-front payment, R&D support and potential milestone and royalty payments (6/20) Avalon MedImmune Pharmaceuticals Inc. (MEDI) Inc.* BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 271 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) BioMarin Pharmaceutical Inc. (BMRN) Serono SA (Switzerland; NYSE:SRA) Collaboration to further develop and commercialize two BioMarin products, Phenoptin and Phenylase, for treating phenylketonuria and possibly other diseases BioMarin gets $25M up front and up to $232M in milestone payments based on the registration of both products in multiple indications, as well as royalties on sales; Serono gets exclusive rights outside the U.S. and Japan (5/16) BioRap Technologies Ltd.* (Israel) BioLineRx Ltd.* (Israel) BioLineRx licensed BL-2030, a soluble receptor that targets cancer cells Terms of the exclusive, worldwide license were not disclosed (6/20) BioWa Inc.* Medarex Inc. (MEDX) Medarex got a second license to BioWa’s Potelligent technology for enhancing antibodydependent cellular cytotoxicity BioWa gets license fees and could receive milestone payments and product royalties; Medarex has nonexclusive rights to develop antibodies for an undisclosed number of targets (5/24) Calando Benitec Ltd. Pharmaceuticals (Australia; ASX: Inc. (majorityBLT) owned by Arrowhead Research Corp.; ARWR) Benitec got exclusive rights to use polymeric nucleic acid delivery technology with its RNAi-based therapeutic for hepatitis C virus Calando gets an up-front payment and potential milestone and royalty payments related to the HCV drug (6/21) Caliper Life Sciences Inc. (CALP) Affymetrix Inc. (AFFX) Affymetrix got nonexclusive rights to use Caliper’s microfluidics technology with GeneChip microarray technologies The deal covers all GeneChip applications; Caliper gets an up-front license fee and royalties on future sales covered under the deal (4/25) Caliper Life Sciences Inc. (CALP) Amphora Discovery Corp.* Amphora agreed to purchase a certain amount of LabChip products over two years Terms of the deal were not disclosed (4/14) Cambridge Antibody Technology Group plc (UK; CATG) BioInvent International AB (Sweden; SSE:BINV) BioInvent got rights to use CAT’s antibody phage-display technology to develop products from its n-CoDeR antibody libraries CAT gets an initial license fee and future payments that depend on how many antibodies BioInvent and its partners develop using the technology; CAT also is entitled to milestone and royalty payments; as part of the deal BioInvent withdrew its opposition to CAT patents filed in Europe (6/3) Service agreement in the field of structure-based drug design Carna and Crystal will provide services to Rigel under undisclosed terms (6/20) Carna Rigel Biosciences Pharmaceuticals Inc.* (Japan) and Inc. (RIGL) Crystal Genomics Inc. (South Korea) 272 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Cellectis SA* (France) Xenogen Corp. (XGEN) Xenogen got a nonexclusive license to a patent covering replacement or insertion of a gene in an eukaryotic genome Xenogen will use the technology for creating knock-in mice; terms of the deal were not disclosed (6/29) Cellectis SA* (France) Celliance (unit of Serologicals Corp.; SERO) Celliance will evaluate Cellectis’ Meganuclease Recombination System The goal is to develop a new generation of cell lines; terms of the deal were not disclosed (5/31) Cell Signaling Technology Inc.* Chiron Corp. (CHIR) CST will perform a pilot project for Chiron using its PhosphoScan technology The goal is to identify phosphorylation sites and prospective biomarkers of protein tyrosine kinase targets; terms of the deal were not disclosed (6/1) Cell Therapeutics Inc. (CTIC) Cephalon Inc. (CEPH) Cephalon acquired Trisenox (arsenic trioxide), a product approved for treating acute promyelocytic leukemia CTI gets $70M in cash and up to $100M more if certain sales and regulatory milestones are achieved; Cephalon also got rights to a joint proteasome inhibitor research program and would pay royalties on any resulting sales from that program; Cephalon will offer jobs to CTI commercial employees (6/13) CeNeS Tripos Inc. Pharmaceuticals (TRPS) plc (UK; AIM:CEN) They entered a new deal to continue a collaboration to advance discovery of COMT inhibitors They already have identified series of compounds active against the target catecholO-methyltransferase; now they will optimize those compounds (4/14) ChemBridge Research Laboratories Inc.* Trimeris Inc. (TRMS) Collaboration to discover and develop small-molecule HIV entry inhibitors, targeting gp41 and gp120 CRL gets funding to support medicinal chemistry efforts and is eligible to receive milestone payments and sales royalties; Trimeris assumes development and commercial responsibilities (6/13) ChemDiv Inc.* Dendreon Corp. (DNDN) They expanded and extended deal under which ChemDiv supplies chemistry services to Dendreon The services support Dendreon’s discovery programs for targeted cancer therapies; terms of the deal were not disclosed (4/1) Chiron Corp. (CHIR) Enanta Pharmaceuticals Inc.* Exclusive deal to develop and commercialize Chiron’s portfolio of hepatitis C virus protease inhibitors Chiron is entitled to milestone and royalty payments and retains certain co-development and commercialization opt-in rights, excluding Asia; Enanta also got nonexclusive rights to certain HCV technology (5/19) CiVentiChem LLC* Tranzyme Pharma Inc.* CiVentiChem will provide medicinal chemistry and other services for Tranzyme The goal is to advance development of Tranzyme’s small-molecule products; terms of the deal were not disclosed (6/29) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 273 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Compugen Ltd. (Israel; CGEN) Biosite Inc. (BSTE) Biosite got rights to develop immunoassay-based diagnostics using biomarkers discovered by Compugen Compugen is entitled to milestone payments and royalties from resulting products; Compugen retains therapeutic rights, and would pay Biosite milestones and royalties on those products (6/20) Corixa Corp. (CRXA) Panbio Ltd. (Australia; ASX:PBO) Panbio acquired technology to help in the development of assays for the diagnosis of two tick-borne diseases Corixa gets an up-front payment, annual maintenance payments and royalties on any resulting product sales (4/12) Cortendo Invest AB* (Sweden) DiObex Inc.* DiObex licensed worldwide rights to inhibitors of cortisol synthesis The technology has applications in metabolic diseases; terms of the deal were not disclosed (4/1 1) Crucell NV (the Netherlands; CRXL) Medarex Inc. (MEDX) Program to optimize the application of Crucell’s STAR technology in bioreactor culture The program will be performed with a fully human antibody developed using Medarex’s UltiMAb technology; terms were not disclosed (6/1) Curis Inc. (CRIS) Genentech Inc. (NYSE:DNA) Collaboration to develop small-molecule modulators of an undisclosed pathway involved in cell proliferation; the pathway is a regulator of tissue formation and repair Curis gets an up-front license fee of $3M and up to $6M more over two years in research support; Curis also could get milestone and royalty payments; the deal, excluding royalties, could be worth $140M to Curis if two products are developed in two indications each; Curis also retains certain rights (4/4) Cytomyx Holdings plc* (UK) Biomoda Inc.* Cytomyx will provide human clinical samples for Biomoda’s program to develop diagnostics The samples will support validation work on Biomoda’s products for detection and targeted treatment of certain cancers; terms of the deal were not disclosed (5/3) Cytos Biotechnology AG (Switzerland; SWX:CYTN) Medarex Inc. (MEDX) They expanded the scope of a November 2002 deal focused on drug targets for immunological diseases to include targets in other areas of interest Cytos gets an up-front payment, and can earn license fees, milestones and royalties; Medarex gets exclusive rights for monoclonal antibodies against the targets and the first right of negotiation for use of the targets in small-molecule drug discovery and as protein therapeutics (4/1) Definiens AG* (Germany) Cenex BioScience AG* (Germany) They formalized an ongoing relationship through the signing of a licensing and co-marketing agreement They will work together in the area of highcontent screening on a worldwide, nonexclusive basis; terms of the deal were not disclosed (5/9) 274 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Depomed Inc. (DEPO) New River Pharmaceuticals Inc. (NRPH) Deal to use Depomed’s oral Gastric Retention delivery technology with New River drug compounds New River may acquire rights to use the technology in up to three compounds; Depomed would get an initial payment and potential milestone and royalty payments for each compound advanced (6/6) Dharmacon Inc. (unit of Fisher Biosciences) Millennium Pharmaceuticals Inc. (MLNM) Dharmacon will deliver a genome-wide siRNA library covering about 22,000 human genes to Millennium The library will enable high-throughput functional genomic studies for target identification and validation; terms of the deal were not disclosed (5/5) Diabetogen Biosciences Inc.* (Canada) TolerRx Inc.* TolerRx acquired rights to the therapeutic use of antiCD3 antibodies in autoimmune diseases TolerRx also got rights to a panel of fully human anti-CD3 antibodies under a licensing agreement between Diabetogen and Abgenix Inc.; terms of the deal were not disclosed (4/4) Dimerix Bioscience Pty. Ltd.* (Australia) Starpharma Holdings Ltd. (Australia; ASX:SPL) They entered a joint venture focused on dendrimer-based GPCR drug discovery and development The venture will use Dimerix’s Collision technology in the effort; Starpharma formed Dimerix and holds a 30% stake in the start-up company (5/1 1) Encysive Revotar BioPharmaceuticals pharmaceuticals Inc. (ENCY) AG (Germany; majority owned by Encysive) Deal under which Revotar would license bimosiamose and certain follow-on compounds The deal is contingent on Revotar’s other stockholders investing additional capital in Revotar, which would reduce Encysive’s ownership to about 14%; Encysive would get royalties on sales (4/26) EndoBiologics International Corp.* VaxGen Inc. (PK:VXGN) Collaboration for research of a vaccine against meningitis serogroup B, using technology developed by EndoBiologics VaxGen will fund proof-of-concept studies for a year; if it then exercises its option, VaxGen would provide additional research funding, while EndoBiologics would be entitled to milestone and royalty payments (5/4) Enlyton Ltd.* Neoprobe Corp. (OTC BB:NEOP) Neoprobe licensed two patents that are related to its RIGS technology The deal provides Neoprobe with an extension of methodology patent protection for the technology; terms were not disclosed (4/5) Epigenomics AG (Germany; FSE:ECX) Qiagen NV (the Netherlands; QGEN) Deal to develop a preanalytical solution portfolio for DNA methylation analysis The goal of the collaboration is to develop diagnostic kit components; Epigenomics gets up-front technology access and license fees, as well as royalties on all research product sales (5/2) Essential Science Ltd.* (UK) Prolysis Ltd.* (UK) They extended collaboration on advancing Prolysis’ bacterial cell biology and antibiotic development programs They now will focus on out- or in-licensing opportunities; terms of the deal were not disclosed (6/17) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 275 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Europroteome AG* (Germany) Miraculins Inc. (Canada; TSE:MOM) Miraculins purchased all rights to a number of patents and discoveries related to the diagnosis and treatment of cancers Europroteome is in receivership; Miraculins has no further milestone or royalty obligations in the deal (6/22) Europroteome AG* (Germany) Genmab A/S (Denmark; CSE:GEN) Genmab acquired all rights to 16 potential targets to treat non-steroid-dependent cancers of epithelial cell origin There are no milestone or royalty obligations in the deal; Europroteome is in insolvency proceedings (5/18) Evolva Biotech SA* (Switzerland) AnalytiCon Discovery GmbH* (Germany) Collaboration to generate and optimize nuclear receptor agonists and related compounds Evolva will create and optimize the agonists; AnalytiCon will de-replicate, identify and scale-up the compounds; terms of the deal were not disclosed (6/30) Exelixis Inc. (EXEL) Genentech Inc. (NYSE:DNA) Collaboration to discover and develop therapeutics targeting cancer, inflammatory diseases and tissue growth and repair; the work focuses on the Notch pathway Exelixis gets up-front and three years of R&D funding totaling $16M; it also is entitled to milestone and royalty payments; Exelixis also has an option to share part of the costs and profits for certain products (6/3) Galapagos NV (Belgium; Euronext:GLPG) Celera Genomics Group (NYSE:CRA) Galapagos will provide technology and adenoviral reagents for Celera research Galapagos will construct recombinant adenoviruses harboring genes selected by Celera; it will receive undisclosed payments for the work (6/20) Genaissance ParAllele Pharmaceuticals BioScience Inc.* Inc. (GNSC) License and co-marketing agreement to provide genetic screening technology and services ParAllele is licensing more than 400 SNPs from Genaissance and combining them with certain public-domain SNPs in an assay panel; Genaissance will be the first company to offer the panel for research uses (4/6) GeneGo Inc.* Exelixis Inc. (EXEL) Exelixis licensed GeneGo’s MetaCore technology The platform is used in drug discovery; terms of the deal were not disclosed (5/13) Genmab A/S (Denmark; CSE: GEN) Serono SA (Switzerland; NYSE:SRA) Serono got worldwide rights to Genmab’s HuMax-TAC, a fully human monoclonal antibody being developed for T-cell-mediated diseases Genmab gets an up-front payment of $2M and is entitled to milestone payments of up to $38M, as well as royalties on sales from any resulting products; the product is in the preclinical stage (5/2) Geron Corp. (GERN) Exeter Life Sciences Inc.* They formed a new company named stART Licensing Inc. for licensing animal cloning technologies The portfolio includes nuclear transfer cloning technology developed at the Roslin Institute; Exeter will provide additional capital for the effort, and own 50.1% of the company; Geron also can get up-front and milestone payments (4/6) 276 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Icoria Inc. (ICOR) Vesta Therapeutics Inc.* Deal under which Icoria will profile Vesta’s adult human liver-derived stem/progenitor cells In return, Icoria will gain access to clinical liver samples for use in validating biomarkers and drug targets (4/27) Icoria Inc. (ICOR) Admet Technologies Inc.* Icoria will characterize Admet’s human adult hepatocytes to improve their value as a predictive toxicology screening tool Admet will use the information to identify cells that could be used in toxicology assays; Icoria retains rights to develop any resulting novel diagnostic biomarkers (4/19) ImmunoGen Inc. (IMGN) Genentech Inc. (NYSE:DNA) They renewed May 2000 agreement giving Genentech certain rights to use ImmunoGen’s TumorActivated Prodrug technology Genentech paid $2M to renew the deal for three years; the original deal was for five years (5/2) ImmunoGen Inc. (IMGN) Genentech Inc. (NYSE:DNA) Genentech licensed rights to use Tumor-Activated Prodrug technology with therapeutic antibodies for an undisclosed target ImmunoGen gets a $1M license payment and is entitled to milestone and royalty payments; the exclusive deal stems from a pact in 2000 giving Genentech rights to test the technology against certain targets (4/28) Ingenuity Systems Inc.* Serono Genetics Institute (France; unit of Serono SA; NYSE:SRA) Serono licensed the Pathways Knowledge Base for use in developing drug discovery and development tools Serono also licensed the Pathways Analysis application; terms of the deal were not disclosed (6/14) InterMune Inc. (ITMN) Three Rivers Pharmaceuticals LLC* Three Rivers acquired worldwide ownership of Amphotec/Amphocil (lipidbased amphotericin B) The product is indicated for treating invasive aspergillosis; terms of the deal were not disclosed (5/24) Intradigm Corp.* Acuity Pharmaceuticals Inc.* Acuity got exclusive rights to Intradigm’s technology for topical and systemic drug delivery for ophthalmic uses They also will collaborate to develop topical formulations of Acuity’s Cand5 compound; Acuity exclusively licensed rights to Intradigm’s siRNA ophthalmic discovery technologies; the deal includes up-front payments and potential milestones and royalties to Intradigm (6/9) Invitrogen Corp. (IVGN) Plexxikon Inc.* Invitrogen will provide kinase screening services on Plexxikon kinase inhibitor libraries Plexxikon intends to develop drugs for oncology, inflammation and other diseases; terms of the service agreement were not disclosed (4/6) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 277 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Kalypsys Inc.* NovImmune SA* (Switzerland) Collaboration to discover and develop small-molecule modulators of the major histocompatibility complex II for treating autoimmune and inflammatory diseases They will pair Kalypsys’ screening technology, chemical library and small-molecule capabilities with NovImmune’s expertise in immunoregulation and MHC Class II-associated biology; terms were not disclosed (6/16) Lexicon Genetics Inc. (LEXG) XOMA Ltd. (XOMA) Collaboration to jointly develop and market antibody drugs for certain targets discovered by Lexicon Lexicon will submit targets and XOMA will generate antibodies to them; costs and profits will be allocated 65% to Lexicon and 35% to XOMA; XOMA will have manufacturing responsibility (6/21) Luminex Corp. (LMNX) Digene Corp. (DIGE) Digene gained access to Luminex’s xMAP bead-based multiplexing technology for use in women’s health diagnostics Digene intends to commercialize in vitro clinical diagnostic tests under the nonexclusive license; terms of the deal were not disclosed (5/5) Medarex Inc. (MEDX) Genmab A/S (Denmark; CSE:GEN) Genmab licensed European and Asian rights to use UltiMAb technology in antibodies raised against the CD4 antigen, including HuMax-CD4 Medarex gets $2M up front and is entitled to milestone and license fee payments up to $12.5M; it also would get royalties that could reach double digits; Genmab now has worldwide rights to HuMax-CD4 (6/30) Medicago Inc.* InterveXion Therapeutics Inc.* Deal to use Medicago’s Proficia Protein Technology to produce monoclonal antibodies designed to treat drug abuse Medicago would get milestone payments to produce the phencyclidine (PCP) antibody; an expanded deal to include another antibody is expected (6/6) Mera Rincon Pharmaceuticals Pharmaceuticals Inc. (OTC BB:MRPI) Inc.* Collaboration to demonstrate the scalability and economics of using microalgae as a protein expression system Mera will use its technology to perform pilot studies on up to six antibodies; Rincon has an option to use the technology to develop its own production capability; terms were not disclosed (5/12) MorphoSys AG (Germany; FSE:MOR) Jerini AG* (Germany) Co-marketing deal between MorphoSys division Antibodies by Design and Jerini subsidiary JPT Peptide Technologies GmbH They will co-market monoclonal antibodies generated by Antibodies by Design and the complementary peptide-based services and products from JPT; each will offer the services of the other (4/18) Morphotek Inc.* Amgen Inc. (AMGN) Morphotek will apply its technology to Amgen cell lines to develop high-titer antibody-producing cell lines Morphotek gets research payments and is entitled to milestone payments in the deal, which is focused on producing cell lines for scalable manufacturing (4/18) Mutabilis SA* (France) Chiron Corp. (CHIR) Chiron Vaccines licensed rights to use Mutabilis technology in development of a prophylactic vaccine Mutabilis is entitled to license fees, milestone payments and royalties on any sales; the target was not disclosed (4/1 1) 278 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Myriad Genetics Inc. (MYGN) Salmedix Inc.* Salmedix got exclusive rights to use the single R-enantiomer of etodolac The license provides additional protection to Salmedix for its cancer candidate SDX-101; Myriad gets $2.5M up front and is entitled to milestone and royalty payments (5/24) NanoCarrier Co. Ltd.* (Japan) Debiopharm SA* (Switzerland) Debiopharm got an option to license a DACH Platin Medicelle platinum-based compound for oncology applications Debiopharm will fund product development; NanoCarrier is entitled to receive milestone payments and royalties on any sales (4/21) Nanogen Inc. (NGEN) DeCode Genetics Inc. (Iceland; DCGN) Nanogen will provide a new genomics assay for single nucleotide polymorphism discovery and screening Terms of the supply and license agreement were not disclosed (4/18) Neovacs SA* (France) Debiopharm SA* (Switzerland) Collaboration to develop Neovacs’ tumor necrosis factor alpha kinoid and related programs Debiopharm will fund the program and make up-front and milestone payments in cash and equity; Neovacs also would be entitled to royalties on sales (6/27) NovImmune SA* (Switzerland) Serono SA (Switzerland; NYSE:SRA) Serono got worldwide rights to two fully human monoclonal antibodies, NI-0401 and NI-0501, which may have potential in autoimmune diseases NovImmune gets a $5M license fee, a $6M equity investment and a convertible loan of up to $6M; it also could get up to $105M in milestone payments, as well as royalties on sales (5/17) Nuevolution A/S* (Denmark) Biovitrum AB* (Sweden) Nuevolution will use its Chemetics technology to discover new drug leads against a Biovitrum target Nuevolution is entitled to certain milestone payments and a share of any future product sales (6/13) OncoMethylome Sciences SA* (Belgium) Exact Sciences Corp. (EXAS) Deal to evaluate certain gene methylation markers for use with Exact’s colon cancer screening technology The markers were identified at Johns Hopkins University and are exclusively licensed to OncoMethylome; terms of the deal were not disclosed (6/7) OriGene Technologies Inc.* Regeneron Pharmaceuticals Inc. (REGN) Regeneron got a license to OriGene’s TrueClone collection of full-length human cDNAs Regeneron will use the technology in its protein expression and target validation platforms; terms were not disclosed (4/27) Penwest Prism Pharmaceuticals Pharmaceuticals Co. (PPCO) Inc.* Prism got exclusive rights to market Penwest’s beta-blocker PW2101 in the U.S. and Canada The product is under review by the FDA for treating hypertension and angina; Penwest got $4M up front and would get $9.5M in milestones if the product was approved by Dec. 31, 2005; Penwest would get royalties of 15% to 18% (4/27) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 279 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Pharming Group NV (the Netherlands; Euronext: PHARM) AgResearch Ltd.* (New Zealand) Partnership under which AgResearch will produce recombinant human lactoferrin for Pharming AgResearch got a research license to technology for producing recombinant proteins; Pharming will have the first right to review products from AgResearch’s protein discovery and R&D projects (6/30) Prostagenics LLC* Innovate Oncology Inc. (OTC BB:IOVO) Innovate acquired rights to capridine-beta, a nitroacridine derivative, for treating prostate cancer Phase I trials for the drug are being planned; terms of the deal were not disclosed (4/8) Protein Design Labs Inc. (PDLI) Genentech Inc. (NYSE:DNA) Genentech sublicensed rights to antibody-drug conjugate technology against the PR1 antigen, which has applications in prostate cancer PDL, which got certain sublicensing rights from Seattle Genetics Inc., is entitled to an up-front licensing fee along with potential milestone and royalty payments (6/22) Protein Design Labs Inc. (PDLI) Seattle Genetics Inc. (SGEN) Seattle Genetics got exclusive rights to PDL’s anti-CD33 program for both unconjugated antibody and antibody-drug conjugate applications PDL gets an up-front fee and is entitled to milestone and royalty payments; the preclinical program has applications in cancer; also, royalties payable by PDL under an existing collaboration were reduced (4/13) Provid Immune Pharmaceuticals Control Inc.* Inc.* Collaboration to develop lead compounds for diseases with immunological causes Provid will use its technologies to develop the lead compounds; terms of the deal were not disclosed (6/17) QLT Inc. (Canada; QLTI) VasoGenix Pharmaceuticals Inc.* Deal to develop a sustainedrelease formulation of VasoGenix’s calcitonin generelated peptide QLT will develop the delivery system for CGRP; VasoGenix has the option to acquire an exclusive worldwide royalty-bearing license to the product (4/1 1) Quadrant Drug Delivery Ltd.* (UK) CoTherix Inc. (CTRX) Deal to develop an extended-release formulation of CoTherix’s Ventavis The product is approved for treating pulmonary arterial hypertension; terms of the deal were not disclosed (4/5) ReOx Ltd.* (UK) Unnamed U.S.based company Deal to co-develop drugs targeting cellular oxygen regulation through the transcription factor hypoxia inducible factor ReOx is getting $9M up front and is entitled to research funding, milestone payments and royalties on any resulting sales; the research has applicability in a number of diseases (4/18) RheoGene Inc.* TissueGene Inc.* Research and license agreement to develop regulated cell therapy treatments for bone restoration and repair The effort will combine TissueGene’s cell therapy technology and RheoGene’s RheoSwitch Therapeutic System to develop nonsurgical treatments for non-union bone fractures, bone wounds and osteoporosis (4/19) 280 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Seattle Genetics Inc. (SGEN) Progenics Pharmaceuticals Inc. (PGNX) and Cytogen Corp. (CYTO) PSMA Development Co. got rights to use antibodydrug conjugate technology for targeting prostatespecific membrane antigen PSMA Development Co. is a joint venture between Progenics and Cytogen; Seattle Genetics gets a $2M access fee, annual maintenance fees and research support payments, as well as potential milestones and royalties (6/20) Seattle Genetics Inc. (SGEN) MedImmune Inc. (MEDI) MedImmune got rights to use antibody-drug conjugate technology with antibodies against a single tumor target Seattle Genetics gets $2M up front and annual maintenance fees and is entitled to milestone and royalty payments; MedImmune also has an option to access the technology for a second antibody program for an additional fee (4/28) Serologicals Corp. (SERO) CXR Biosciences Ltd.* (UK) Collaboration to establish a battery of in vitro screens for improving selection of candidate drug molecules Serologicals subsidiary Upstate Group will work with CXR in the effort; terms of the deal were not disclosed (6/22) Sigmoid Biotechnologies Ltd.* (Ireland) Inncardio Inc. (OTC BB:INDO) Deal to develop new formulations of established drugs using Sigmoid’s delivery and formulation technology Neither the drugs nor the terms of the deal were disclosed (4/18) To-BBB BV* (the Netherlands) Genmab A/S (Denmark; CSE:GEN) Genmab will evaluate To-BBB’s technology for delivering antibodies across the bloodbrain barrier Genmab has an option to license the technology for use with two antibodies; To-BBB is eligible to receive milestone and royalty payments (5/24) TranXenoGen Inc.* A.C.T. Holdings Inc. (OTC BB:ACTH) A.C.T. and subsidiary Advanced Cell Technology Inc. got an option for exclusive rights to cloning patents Separately, A.C.T. acquired rights to a cloning technology known as “cell fusion” and patents related to gene trap technology; terms of the deal were not disclosed (5/19) Valentis Inc. (VLTS) Biolitec AG (Germany; FSE:BIB) Biolitec got worldwide rights to use pegylated liposomal technology from Valentis to develop new drug formulations Valentis gets an up-front payment and is eligible to receive milestone payments and royalties on any resulting sales (6/22) Vical Inc. (VICL) AnGes MG Inc. (Japan; Tokyo:4563) AnGes gained exclusive rights to use Vical’s nonviral gene delivery technology for cardiovascular applications The license covers DNA-based products encoding hepatocyte growth factor; Vical gets $1M up front, and is eligible for milestone and royalty payments (5/24) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 281 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Xantos Biomedicine AG* (Germany) NascaCell IP GmbH* (Germany) and PSF Biotech AG* (Germany) The three companies formed a consortium to identify and develop new drugs for the inhibition of tumor angiogenesis The collaboration, using an aptamer-based approach, will integrate the technology platforms of the three companies; the PADDION consortium will receive initial funding from the BioChancePlus program of the German Federal Ministry of Education and Research (4/13) THIRD QUARTER Abmaxis Inc.* MaimoniDex RA Ltd.* (Israel) Deal to jointly develop a human monoclonal antibody for treating rheumatoid arthritis and other inflammatory diseases Abmaxis will humanize and optimize the murine antibody from MaimoniDex and be entitled to up-front, milestone and royalty payments (9/21) Advancis Pharmaceutical Corp. (AVNC) Undisclosed private company Advancis agreed to sell U.S. rights to the Keflex brand of cephalexin to the company Advancis got $1M up front and expects to get $1 1M when the deal closes, plus up to $3M in milestone payments for the approved antibiotic (9/15) Aegis Therapeutics LLC* Undisclosed company The unnamed partner licensed rights to use Intravail delivery technology with undisclosed pediatric therapeutics The Intravail technology allows intranasal delivery of peptide and protein therapeutics; terms of the deal were not disclosed (8/1) Aeres Biomedical* (UK) Lpath Therapeutics Inc.* Deal to humanize Lpath’s sphingomab murine antibody The antibody has shown activity against cancers; terms of the deal were not disclosed (9/19) Agilix Corp.* Protana Inc.* Protana got a nonexclusive license to Agilix’s i-PROT proteomics technology Protana will use the technology in its proteomic services, including biomarker discovery; terms were not disclosed (7/21) Aldevron LLC* CytoGenix Inc. (OTC BB:CYGX) Aldevron will test the activity of a CytoGenix DNA vaccine against hepatitis B Aldevron will use use its Genetic Immunization and Antibody technology in the effort; terms were not disclosed (8/2) Alnylam Qiagen NV Pharmaceuticals (the Netherlands; Inc. (ALNY) QGEN) Qiagen got nonexclusive rights to provide research products and services in RNA interference Alnylam’s Kreutzer-Limmer patent family covers small interfering RNAs and their use to mediate RNAi in mammalian cells; terms of the deal were not disclosed (9/21) Alnylam MWG Biotech Pharmaceuticals AG (Germany; Inc. (ALNY) FSE:NWUG) MWG got nonexclusive rights to provide research products and services under Alnylam RNA interference patents Terms of the license to the KreutzerLimmer patent family were not disclosed (7/25) 282 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Alnylam Nastech Pharmaceuticals Pharmaceutical Inc. (ALNY) Co. Inc. (NSTK) Nastech got an exclusive license to develop and sell RNAi therapeutics directed against TNF-alpha Alnylam gets up-front and annual payments and is entitled to milestone payments and royalties on sales of covered products (7/20) Alnylam Eurogentec Pharmaceuticals SA* (Belgium) Inc. (ALNY) Eurogentec got nonexclusive rights to provide research products and services under Alnylam RNA interference patents The Kreutzer-Limmer patent family covers short interfering RNAs and their use to mediate RNAi in mammalian cells; terms of the deal were not disclosed (7/12) Amgen Inc. (AMGN) ViaCell Inc. (VIAC) ViaCell licensed rights to use recombinant human granulocyte-colony stimulating factor, expanding an earlier deal License covers development of a cellular therapy product to treat hematological malignancies and genetic diseases; Amgen got a warrant to purchase 200,000 ViaCell shares; further terms were not disclosed (8/30) Aphton Corp. (APHT) VaxGen Inc. (VXGN) VaxGen’s South Korean joint venture Celltrion got rights to the cancer antibody IGN31 1 in certain Asian countries, including Japan Igeneon AG, Aphton’s subsidiary in Austria, potentially will get $6M in milestone payments and royalties on sales; Celltrion also will provide development and manufacturing services related to the product (7/25) Argenta Discovery Ltd.* (UK) Cellzome Inc.* Companies entered a drug discovery collaboration Argenta will apply its medicinal chemistry, assay development and screening capabilities in the deal, terms of which were not disclosed (8/29) Array BioPharma Inc. (ARRY) InterMune Inc. (ITMN) Extended and expanded a 2002 deal to develop smallmolecule inhibitors of the hepatitis C virus NS3/4 protease InterMune is funding preclinical efforts at Array and would develop and sell resulting products; Array is entitled to milestone and royalty payments (7/19) AutoGenomics Inc.* Targeted Molecular Diagnostics LLC* Three-year deal to develop cancer biomarkers on the AutoGenomics Infiniti platform Terms of the deal were not disclosed (7/27) Axordia Ltd.* (UK) Serologicals Corp. (SERO) Exclusive deal to co-develop antibody markers from Axordia’s human embryonic stem cell lines Serologicals subsidiary Chemicon International Inc. would commercialize any resulting antibody research tools; terms were not disclosed (9/30) Banyan Biomarkers Inc.* Biosite Inc. (BSTE) Deal to review cerebrovascular injury targets discovered with Banyan’s animal model of cerebral injury Biosite may select targets that Banyan nominates, and then would make antibodies to those targets, which would be used to create assays; terms of the deal were not disclosed (8/1) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 283 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Cellectis SA* (France) Biogen Idec Inc. (BIIB) Cellectis will develop a custom meganuclease recombination system for Biogen The system will be designed to enable reproducible high-yield production of target proteins in mammalian cells; terms were not disclosed (9/21) Cellectis SA* (France) Ozgene Pty. Ltd.* (Australia) Ozgene got a nonexclusive license to a patent covering replacement or insertion of a gene in a eukaryotic genome Ozgene got rights related to the creation, development and sales of knock-in mice; terms of the deal were not disclosed (7/12) ChemDiv Inc.* Euroscreen SA* (Belgium) Partnership to discover and develop drugs against GPCR family chemokine targets They intend to combine expertise in the effort and share income from partnering clinical and preclinical candidates (7/1) Chiron Corp. (CHIR) and Ortho-Clinical Diagnostics Inc. OraSure Technologies Inc. (OSUR) OraSure got nonexclusive rights to certain patents covering hepatitis C virus OraSure intends to use the technology in a diagnostic product; it will make up-front and royalty payments for the license (8/2) Crucell NV (the Netherlands; CRXL) and DSM Biologics (the Netherlands) Chiron Corp. (CHIR) Chiron got rights to test the PER.C6 cell line for use in manufacturing a prophylactic hepatitis C vaccine candidate Terms of the deal were not disclosed (8/16) Crucell NV (the Netherlands; CRXL) and DSM Biologics (the Netherlands) Symphogen A/S* (Denmark) Symphogen got rights to use the PER.C6 cell line for producing its recombinant polyclonal antibodies Symphogen will pay a signing fee and annual maintenance fees; further terms were not disclosed (7/15) Cyclacel Group plc* (UK) Genzyme Corp. (GENZ) Genzyme got an option to license two preclinical CDK inhibitors for treating renal diseases and certain related conditions The deal on the cyclin-dependent kinase inhibitors does not include rights in oncology or other areas; Genzyme will evaluate the compounds under undisclosed terms (9/14) DeveloGen AG* (Germany) Debiopharm SA* (Switzerland) Debiopharm got rights to develop PTR-262, a peptide drug for the treatment of myasthenia gravis Debiopharm intends to out-license the product later; DeveloGen is entitled to milestone and royalty payments (8/16) DiNonA Inc.* (South Korea) EvoGenix Ltd. (Australia; ASX:EGX) EvoGenix licensed worldwide rights to an antibody for treating leukemia Terms of the deal were not disclosed (9/19) 284 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) DxS Ltd.* (UK) Cepheid Inc. (CPHD) Cepheid got rights to use Scorpions probe technology in a number of applications Cepheid intends to apply the technology to industrial markets; its license excludes clinical diagnostics, wine production and detection of chemicals used in agriculture (7/20) EidogenSertanty Inc.* Medisyn Technologies Inc.* Medisyn got a license to the Kinase Knowledgebase from Eidogen The product is a database of structureactivity relationships and chemical synthesis data focused on protein kinases (9/7) Eiffel Technologies Ltd. (Australia; ASX:EIF) MAP Pharmaceuticals Inc.* MAP got exclusive rights to use Eiffel’s technology for the pulmonary delivery of insulin and the delivery of steroids with or without beta agonists Eiffel gets $0.6M to fund a specific program of process development work; it also is entitled to milestone payments and royalties on any resulting sales (9/22) Evotec AG (Germany; FSE: EVT) Genedata AG* (Switzerland) Co-marketing deal to offer high-content and highthroughput screening They will combine products to offer a onestop solution for potential customers (9/13) Galapagos NV (Belgium; Euronext:GLPG) Amsterdam Molecular Therapeutics BV* (the Netherlands) Collaboration to develop treatments for acute spinal cord and peripheral nerve damage The collaboration also includes the Netherlands Institute for Brain Research and the Vrije Universiteit Amsterdam and is being supported by a grant from the Dutch government (9/14) GeneThera Inc. (OTC BB: GTHA) Xpention Genetics Inc. (OTC BB:XPNG) GeneThera will provide research services for development of a cancer detection test in animals and humans Under one contract GeneThera will get $20,000 per month for one year to develop a test for animals; GeneThera will get $10,000 per month under a second contract to extend the technology into human testing (7/19) Genmab A/S (Denmark; CSE: GEN) Serono SA (Switzerland; NYSE:CRA) Serono got worldwide rights to HuMax-CD4, a fully human monoclonal antibody for treating T-cell lymphomas that’s in Phase III trials Genmab gets a $20M license payment and a $50M equity investment from Serono at a premium; Genmab could get up to $145M more in regulatory and sales milestones, as well as royalties on resulting sales (8/18) Hyalose LLC* Meditech Research Ltd. (Australia; ASX:MTR) Collaboration to evaluate hyaluronic acid molecules for their ability to act as targeting agents in drug delivery systems The HA molecules are produced using recombinant technology developed at the University of Oklahoma and licensed to Hyalose; terms of the deal were not disclosed (7/7) Iconix will provide chemogenomic analyses on candidate compounds from Neurocrine Iconix will apply its DrugMatrix technology to at least 12 Neurocrine compounds; terms of the deal were not disclosed (7/12) Iconix Neurocrine Pharmaceuticals Biosciecnes Inc.* Inc. (NCRX) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 285 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Icoria Inc. (OTC BB:ICOR) Unnamed company Icoria will provide microarray expression services to the undisclosed company Services under the contract will be performed by Icoria’s gene expression profiling unit Paradigm Array Labs (9/8) Icoria Inc. (ICOR) Isis Pharmaceuticals Inc. (ISIS) Agreement to identify biomarkers of toxicity in animal models Icoria will use its metabolomics platform to characterize differences in biochemical profiles between treated and untreated animal subjects and to identify those biochemicals that are specifically affected by treatment (8/23) ImmunoGen Inc. (IMGN) Genentech Inc. (NYSE:DNA) Genentech got exclusive rights to use ImmunoGen’s TumorActivated Prodrug technology with antibodies to an undisclosed target ImmunoGen gets a $1M license payment and is entitled to milestone and royalty payments; Genentech now has taken three licenses to the TAP technology (7/26) Institute of Cell Therapy* (Ukraine) Stem Cell Therapy International Inc. (OTC BB:ATYD) Stem Cell got global rights for the supply of stem cells and the use of 26 related patents Terms of the deal were not disclosed (9/19) Isis iCo Therapeutics Pharmaceuticals Inc.* Inc. (ISIS) iCo got exclusive rights to develop and sell ISIS 13650, a second-generation antisense drug Isis gets cash and a note convertible into iCo equity up front, along with potential milestone and royalty payments; the drug initially will be developed for eye diseases (8/25) Jurilab Ltd.* (Finland) Nanogen Inc. (NGEN) Nanogen acquired certain rights to develop diagnostic products based on genes and markers discovered by Jurilab; it also will distribute Jurilab’s pharmacogenomic products and services Nanogen made a €1.25M investment for a stake of less than 20% in Jurilab and will invest that much again in six months; Nanogen also got an option to purchase all of Jurilab; terms were not disclosed (7/26) Key Organics Ltd (UK) Reaction Biology Corp.* They created a joint venture to engage in high-throughput drug discovery The plan is to identify potential drug compounds and then to partner or sell them to pharmaceutical companies (8/29) Large Scale Biology Corp. (LSBC) BioCatalytics Inc.* Collaboration to apply their technologies to develop improved enzymes for chemical synthesis LSBC gets a license fee for use of its proteinimprovement technologies and would get royalties on any resulting sales (8/17) Medarex Inc. (MEDX) ImClone Systems Inc. (IMCL) ImClone licensed rights to use Medarex’s UltiMAb system to develop human antibody product candidates Medarex will get license fees and could receive milestone and royalty payments from resulting products (9/12) 286 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Medicago Inc.* (Canada) Acambis plc (UK; ACAM) Deal to evaluate the expression of recombinant vaccines using Medicago’s plant-based Proficia system Medicago is entitled to milestone payments in the deal (9/27) Mimitopes Pty. Ltd. (Australia; unit of PharmAust Ltd.; ASX:PAA) Phylogica Ltd. (Australia; ASX:PYC) Partnership to pool technologies to develop nextgeneration peptide drugs They will use Phylogica’s Phylomer and Mimitopes’ Synthase technologies in the effort; terms of the deal were not disclosed (8/15) NovaThera Ltd.* (UK) Pharming Group NV (the Nertherlands; Euronext:PHARM) Collaboration to combine NovaThera’s biomaterial products with Pharming’s recombinant proteins NovaThera is entitled to milestone and royalty payments in the deal; Pharming gets rights to resulting products (7/12) OctoPlus Technologies BV* (the Netherlands) SingVax Pte. Ltd.* (Singapore) Collaboration to co-develop a single-shot Japanese encephalitis vaccine SingVax will be responsible for various development activities; OctoPlus will be responsible for formulation work; they will share costs and any profits (9/26) Odyssey Thera Inc.* Lexicon Genetics Inc. (LEXG) Odyssey will characterize the pathway activity of certain Lexicon compounds in human cells Terms of the deal were not disclosed (7/20) Oxxon Therapeutics Ltd.* (UK) Bavarian Nordic A/S (Denmark; CSE:BAVA) Cross-licensing deal covering modified vaccinia ankara and PrimeBoost technologies Oxxon got certain rights to MVA technology and Bavarian Nordic got rights to PrimeBoost; each would pay the other royalties on any resulting sales (7/1) Peregrine Medarex Inc. Pharmaceuticals (MEDX) Inc. (PPHM) Medarex got rights to develop and sell its anti-PSMA monoclonal antibody conjugated to therapeutic agents for use in cancer therapies Peregrine gets an up-front payment and annual maintenance fees, as well as potential milestones and royalties for the license to its Vascular Targeting Agent technology platform (8/25) Prima Biomed Ltd. (Australia; ASX:PRR) Xencor Inc.* Xencor got a nonexclusive license to use Fc receptor technology for research and an option to use the technology in development Prima subsidiary Arthron Pty. Ltd. gets an up-front fee and annual license fees and would get additional fees and milestone payments, if Xencor exercises its development option (9/8) Protein Design Labs Inc. (PDLI) Biogen Idec Inc. (BIIB) Deal to jointly develop and market three Phase II PDL antibodies: daclizumab, M200 (volociximab) and HuZAF (fontolizumab) PDL gets $40M up front and a $100M equity investment; it also could earn up to $560M in development milestones and $100M in commercialization milestones; they will share costs and profits in the U.S. and Europe, and PDL would get royalties elsewhere (8/2) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 287 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) RenaMed Biologics Inc.* Genzyme Corp. (GENZ) Deal to develop and sell RenaMed’s Bio-Replacement Therapy for treating acute renal failure Genzyme will spend $23M through 3Q:06 to support development and could pay $20M in development milestones, plus regulatory milestones; costs and any profits will be equally shared (9/28) RheoGene Inc.* Xenogen Corp. (XGEN) Xenogen got rights to use the RheoSwitch System to develop transgenic mice They also will collaborate on projects aimed at controlling delivery and regulating expression of RNAi; terms were not disclosed (9/14) RheoGene Inc.* Cellumen Inc.* Cellumen got nonexclusive rights to use RheoGene’s RheoSwitch and RheoPlex technologies Cellumen intends to develop systems cell biology screening products and offer them to drug developers; they also will develop and validate mammalian cell lines; terms were not disclosed (7/26) Rosetta Genomics Ltd.* (Israel) Ambion Inc.* Ambion got access to microRNA sequences discovered by Rosetta Ambion will adapt its microRNA platforms to detect, quantify and functionally characterize the sequences for use in developing products for research (9/12) Santhera Biovitrum AB* Pharmaceuticals (Sweden) AG* (Switzerland) Biovitrum got worldwide rights to Santhera’s DPP-IV inhibitor program for treating Type II diabetes and other metabolic diseases Santhera gets €4M up front, and gets a certain percentage of future revenues, which could include milestones and royalties from sublicenses (8/17) Sareum Holdings plc (UK: AIM:SAR) Infinity Pharmaceuticals Inc.* Sareum will provide protein structure determination services for Infinity Sareum will attempt to show how Infinity’s drug candidates interact with target receptor proteins; terms were not disclosed (9/22) Scancell Ltd.* (UK) GTC Biotherapeutics Inc. (GTCB) Collaboration centered on Scancell’s SC101 anticancer monoclonal antibody, which targets Lewis y/b They will evaluate expression of the MAb using GTC’s transgenic production platform, an effort that could lead to a collaboration on clinical development; terms were not disclosed (7/28) SIRS-Lab GmbH* (Germany) Biosite Inc. (BSTE) Collaboration to evaluate and potentially commercialize sepsis markers Biosite will make antibodies to targets provided by SIRS-Lab; terms of the deal were not disclosed (8/25) Sonus ImaRx Pharmaceuticals Therapeutics Inc. (SNUS) Inc.* ImaRx got a license to fluorocarbon-based oxygendelivery technology ImaRx’s sublicense on four patents is exclusive; Sonus would get royalties on any resulting sales (7/1 1) SR Pharma plc (UK:AIM:SRA) Introgen is supporting work at SR Pharma through a $3M investment Introgen gained an 8.3% stake in SR Pharma and expanded its presence into Europe; further terms were not disclosed (7/28) 288 Introgen Therapeutics Inc. (INGN) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Stem Cell Sciences plc (UK; AIM:STEM) Deltagen Inc. (PK:DGENQ) Deltagen licensed rights to Stem Cell’s IRES technology to make and sell knockout mice Stem Cell gets $1.2M up front royalties on resulting sales and will be provided genetically engineered mice (9/5) StemCells Inc. (STEM) ReNeuron Holdings plc* (UK) ReNeuron licensed rights to use c-mycER conditionally immortalized adult human neural stem cell technology StemCells got an equity interest in ReNeuron and a cross-license to exclusively use ReNeuron’s technology for certain diseases and conditions; each would pay the other milestones and royalties on resulting products (7/6) Symphogen A/S* Cambridge (Denmark) Antibody Technology Group plc (UK; CATG) Patent license agreement giving Symphogen access to CAT’s antibody phage display patents for research purposes and to develop and commercialize antibody products Symphogen made an up-front payment and exercised its first option to develop and commercialize Sym00 1 for idiopathic thrombocytopenic purpura and hemolytic disease of newborns; as a result, Symphogen paid a product license fee and may make future milestone and royalty payments to CAT (8/23) Tolerance Therapeutics Inc.* MacroGenics Inc.* MacroGenics acquired an anti-CD3 monoclonal antibody for treating Type I diabetes and other autoimmune diseases The product has been in a Phase I trial; terms of the deal were not disclosed (7/18) VasGene Therapeutics Inc.* MedImmune Inc. (MEDI) Deal to develop cancerfocused monoclonal antibodies targeting the EphB4 subfamily of receptor tyrosine kinases, as well as its ligand, EphrinB2 VasGene will provide R&D support and is entitled to an up-front fee along with milestone and royalty payments; MedImmune will develop and commercialize any resulting products (9/8) VivoQuest Inc.* XTL Biopharmaceuticals Ltd. (Israel; XTLB) XTL got exclusive rights to VivoQuest technology, including HCV compounds and its compound library VivoQuest got an up-front payment of $1.4M in XTL stock; it also is entitled to development and commercialization milestone payments under the asset-purchase deal (9/21) FOURTH QUARTER Abmaxis Inc.* BioArctic Neuroscience AB* (Sweden) Collaboration to develop a human monoclonal antibody for treating Alzheimer’s disease Abmaxis will further optimize and humanize BioArctic’s murine antibodies; Abmaxis gets an up-front license fee and could receive milestone and royalty payments (10/6) Accelr8 Technology Corp. (AMEX:AXK) Promega Corp.* Deal to develop Accelr8’s OptiChem surface chemistry for use in microarraying slides They will explore new techniques in microarray research using their respective technologies (10/17) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 289 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) ACE BioSciences A/S* (Denmark) Crucell NV (the Netherlands; CRXL) Crucell licensed bacterial antigens to accelerate its bacterial antibody discovery program The license was granted by ACE and the Brigham and Women’s Hospital; terms of the deal were not disclosed (1 1/2) ActiveSight (unit of Rigaku Americas Corp.) Inpharmatica Ltd.* (UK) ActiveSight will provide structural biology services to Inpharmatica The deal focuses on co-crystallography by ActiveSight of certain Inpharmatica small molecules with a human drug target protein; ActiveSight is entitled to up-front and milestone payments (1 1/17) ActiveSight (unit of Rigaku Americas Corp.) Ambit Biosciences Corp.* Protein crystallography services agreement to advance drug discovery at Ambit The deal covers the co-crystallization of Ambit molecules with proteins expressed by ActiveSight; terms were not disclosed (1 1/1) Affitech A/S* (Norway) XOMA Ltd. (XOMA) Collaboration and cross-license agreement covering antibodyrelated technologies Affitech gets a license to use XOMA’s bacterial cell expression technology; XOMA gets rights to use Affitech’s naïve antibody library; terms were not disclosed (1 1/29) Affymetrix Inc. (AFFX) Vita Genomics* (Taiwan) Vita got nonexclusive access to Affymetrix microarray technology to develop and market in vitro diagnostics The license covers tests for alpha interferon treatment response in hepatitis patients, and for early onset and allergic asthma in infants and young children (12/26) Affymetrix Inc. (AFFX) PathWork Informatics Inc.* PathWork got long-term, nonexclusive access to microarray technology from Affymetrix PathWork plans to develop and market in vitro diagnostic tests for cancer under the Powered by Affymetrix program; terms were not disclosed (1 1/1) Aradigm Corp. (ARDM) United Therapeutics Corp. (UTHR) Deal to develop an inhaled, liposomal formulation of treprostinil, a drug approved for treating pulmonary arterial hypertension The goal is to deliver the prostacyclin analogue named Remodulin in Aradigm’s AERx System; Aradigm is entitled to development fees, milestone payments and royalties on any resulting sales (10/24) Argenta Discovery Ltd.* (UK) Genentech Inc. (NYSE:DNA) Two-year deal to use Argenta technologies to discover compounds against a Genentech drug target Terms of the deal were not disclosed but do provide options to expand the relationship (12/15) Array BioPharma Inc. (ARRY) Genentech Inc. (NYSE:DNA) They extended for a second time a January 2004 deal to discover small-molecule drugs for treating cancer Array could get up to $50M in research funding over three years; Array also is entitled to milestone and royalty payments (10/13) 290 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Avantogen Ltd. (Australia; ASX:ACU) Hawaii Biotech Inc.* Nonexclusive deal under which HawaiiBio will evaluate Avantogen’s GPI-0100 adjuvant HawaiiBio plans to develop vaccines for infectious diseases; Avantogen is entitled to sublicense fees, milestone payments and royalties on resulting sales (10/12) Avidia Inc.* MedImmune Inc. (MEDI) Collaboration to develop anticancer products targeting the receptor tyrosine kinase cMET They will develop two other targets using Avidia’s Avimer technology; Avidia is entitled to an up-front fee, milestone payments and royalties on any resulting sales (10/20) Avigen Inc. (AVGN) Genzyme Corp. (GENZ) Genzyme is acquiring all Avigen assets related to adeno-associated vectors, except those related to pain Avigen gets $12M up front for the gene therapy program and is eligible to receive milestone and royalty payments on resulting products (12/21) Biolex Therapeutics Inc.* Kringle Pharma Inc.* (Japan) Biolex will use its LEX System to create a commercial line for Kringle’s NK4 protein NK4 is an elastase-generated fragment of hepatocyte growth factor, being developed for cancers; terms were not disclosed (10/27) BioSpecifics Technologies Corp.* Auxilium Pharmaceuticals Inc. (AUXL) Auxilium exercised its option expanding its rights to an additional indication for the injectable enzyme AA4500 Auxilium gets exclusive rights to the product for treating frozen shoulder syndrome; it already had rights to the drug in treating Dupuytren’s and Peyronie’s diseases (12/20) Biota Holdings Ltd. (Australia; ASX:BTA) MedImmune Inc. (MEDI) Deal to develop Biota’s small-molecule compounds designed to prevent and treat respiratory syncytial virus Biota gets $5M up front and R&D payments and could get up to $107.5M in milestone payments, as well as royalties on sales; Biota retained marketing rights in Australia, China and Southeast Asia (12/14) Bio3 Research Srl* (Italy) and Creabilis Therapeutics SpA* (Italy) Cephalon Inc. (CEPH) Deal to evaluate the compound K252a for treating psoriasis and restenosis All three companies have certain rights to the compound; Cephalon gets an exclusive option to develop and sell resulting products (12/1) BioTrove Inc.* Sirtris Pharmaceuticals Inc.* BioTrove will perform highthroughput screening on Sirtris targets BioTrove will use its RapidFire Lead Discovery service in the effort, which represents an expansion of an existing deal (1 1/9) ChemDiv Inc.* ProQinase GmbH* (Germany) They formed a partnership for the discovery and preclinical development of kinase inhibitors They will share development costs and any revenues from the planned out-licensing of optimized leads (1 1/7) Accentia got U.S. rights to an intranasal steroid product for treating allergic rhinitis Collegium plans to file a supplemental NDA in 2006 for the aqueous nasal spray formulation; terms of the deal were not disclosed (12/6) Collegium Accentia BioPharmaceuticals pharmaceuticals Inc.* Inc. (ABPI) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 291 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) CombinatoRx Inc.* Angiotech Pharmaceuticals Inc. (Canada; ANPI) Deal to develop drug devices and therapeutics built from CombinatoRx’s expertise in drug combinations; Angiotech has an option to get exclusive licenses in certain applications CombinatoRx gets an up-front license fee of $27M plus a $15M equity investment; Angiotech may license up to 10 compounds under the deal and may license up to five more for $2M each; CombinatoRx could get milestones of up to $30M per compond and royalties on any resulting sales (10/3) Cresset BioMolecular Discovery Ltd.* (UK) Galapagos NV (Belgium; Euronext:GLPG) Deal to develop compound libraries based on Cresset’s molecular fields software Galapagos division BioFocus has an option to license the technology for medicinal chemistry projects for itself and third parties (12/15) Crucell NV (the Netherlands; CRXL) and DSM Biologics (the Netherlands) ZyStor Therapeutics Inc.* ZyStor got rights to evaluate the PER.C6 cell line for use in the manufacturing of a specific therapeutic protein Terms of the deal were not disclosed (12/21) Crucell NV (the Netherlands; CRXL) Genzyme Corp. (GENZ) Genzyme got a nonexclusive research license for producing monoclonal antibodies Details on the STAR license were not disclosed (12/19) Crucell NV (the Netherlands; CRXL) Vakzine Projekt Management GmbH* (Germany) VPM got rights to use the PER.C6 cell line to develop a vaccine and diagnostics for an undisclosed infectious disease Crucell gets a research license fee and annual maintenance fees; further terms were not disclosed (12/8) Crucell NV (the Netherlands; CRXL) and DSM Biologics (the Netherlands) IQ Corp.* (the Netherlands) IQ got a license to use the PER.C6 cell line for producing monoclonal antibodies Crucell and DSM are entitled to a signing fee and annual maintenance fees; further terms were not disclosed (10/19) Curis Inc. (CRIS) Genentech Inc. (NYSE:DNA) Genentech extended funding of their deal to develop cancer drugs through June 2006 Curis gets another $1.25M to support personnel working on Hedgehog antagonist technologies (10/13) Dyax Corp. (DYAX) Debiopharm SA* (Switzerland) They restructured deal for developing Dyax’s DX-890, an inhibitor of neutrophil elastase, for treating pulmonary disorders Debiopharm gets exclusive rights to a native form of DX-890 in cystic fibrosis and acute respiratory distress syndrome; Dyax gets a milestone payment and retains rights to milestones and royalties from the DX-890 programs (12/20) EidogenSertanty Inc.* Kalypsys Inc.* Collaboration focused on the discovery of small-molecule compounds for anti-inflammatory indications Eidogen will design a virtual library of compounds expected to be active against a Kalypsys target; terms of the deal were not disclosed (12/14) 292 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) EidogenSertanty Inc.* KAI Pharmaceuticals* Services deal under which Eidogen will characterize protein kinase C regulatory domains for KAI Eidogen will use technologies from its DirectDesign Discovery Service in the deal; terms were not disclosed (10/18) ExonHit Therapeutics SA* (France) Affymetrix Inc. (AFFX) Deal to combine Affymetrix’s GeneChip microarray platform and ExonHit’s alternative RNA splicing technologies The first arrays with the ExonHit SpliceArray content are expected to be available by the end of 2005; ExonHit is entitled to license payments (10/17) 4AZA Bioscience NV* (Belgium) Gilead Sciences Inc. (GILD) Deal to develop compounds discovered by 4AZA for treatment of hepatitis C virus infection 4AZA gets an up-front payment and equity investment from Gilead, which gets worldwide rights; 4AZA also will get research funding and could get milestone and royalty payments (1 1/30) Galapagos NV (Belgium; Euronext:GLPG) Prolysis Ltd.* (UK) They extended deal from earlier in 2005 focused on a Prolysis program in antibiotic resistance Galapagos division BioFocus is doing leadoptimization work to identify dual enzyme inhibitors that overcome the problem of resistance; Prolysis will fund work through 2006 (12/30) Galapagos NV (Belgium; Euronext:GLPG) Amgen Inc. (AMGN) They extended deal under which Galapagos division BioFocus is providing biology and chemistry services for Amgen The deal will run through 2006 and focus on Amgen’s ion channel lead discovery programs; Galapagos gets $2.3M up front and up to a total of $30M in access and researches fees, milestone payments and bonuses (12/7) Galapagos NV (Belgium; Euronext:GLPG) Senexis Ltd.* (UK) Expanded deal to optimize Senexis compounds being developed for Alzheimer’s disease Galapagos division BioFocus will provide medicinal chemistry services to Senexis; terms of the deal were not disclosed (12/2) Galapagos NV (Belgium; Euronext:GLPG) Idenix Pharmaceuticals Inc. (IDIX) Galapagos division BioFocus will provide compound collections and medicinal chemistry services to Idenix The focus is on hepatitis and HIV programs at Idenix; Galapagos can earn up to $2.5M over the two-year collaboration (1 1/24) Galapagos NV (Belgium; Euronext:GLPG) Serono SA (Switzerland; NYSE:SRA) Galapagos will supply compounds from its SoftFocus collection for use in Serono’s drug discovery programs Also, medicinal chemistry services being provided by Galapagos division BioFocus will be expanded; Galapagos gets technology access fees and fees for chemistry services (10/18) They entered technology transfer and screening agreements Details were not disclosed; as part of the deal, Galileo gained an equity stake in Edison (1 1/29) Galileo Edison Pharmaceuticals Pharmaceuticals Inc.* Inc.* BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 293 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Genedata AG* (Switzerland) TransTech Pharma Inc.* TransTech licensed the Genedata Screener highthroughput screening analysis software TransTech will use the technology to enhance small-molecule drug development; terms of the multiyear deal were not disclosed (12/14) Genedata AG* (Switzerland) Neurocrine Biosciences Inc. (NBIX) Neurocrine licensed the Genedata Expressionist gene expression analysis system Neurocrine will use the technology for biomarker discovery and in silico prediction, in discovery programs focused on neurological and endocrine-related diseases (12/7) Genedata AG* (Switzerland) Signature Diagnostics AG* (Germany) Signature licensed Genedata software to help identify gene expression profiles Terms of the license to the Genedata Expressionist software solution were not disclosed (1 1/1) GeneGo Inc.* Velcura Therapeutics Inc.* Velcura licensed GeneGo’s MetaCore database product under a multiyear deal Velcura will use the technology for analysis of gene expression and proteomic and other data related to bone formation (1 1/9) GenOway* (France) Invitrogen Corp. (IVGN) Deal to create a services platform offering RNAi vector design through creation of RNAi transgenic rodent models Each company will contribute technology to the effort; revenues from the co-marketing deal would be shared on an undisclosed basis (12/15) GenVec Inc. (GNVC) Mytogen Inc.* Mytogen acquired GenVec’s myoblast cell therapy program; it will keep most employees who managed the program GenVec is eligible to receive milestone and royalty payments in the deal; the technology is being developed to treat congestive heart failure (12/29) GenVec Inc. (GNVC) Unnamed entity Letter of intent calls for sale of GenVec’s myoblast cell therapy program for treating congestive heart failure GenVec would get royalties on any resulting revenues; the technology was acquired through GenVec’s 2003 merger with Diacrin Inc. (10/18) GPC Biotech AG (Germany; GPCB) Pharmion Corp. (PHRM) Pharmion got rights to the Phase III cancer product satraplatin in Europe, Turkey, the Middle East, Australia and New Zealand GPC gets $37.1M up front; they will share development costs; GPC could get $30.5M in milestone payments and up to $75M more for up to five subsequent EMEA approvals; another $105M in sales milestones could be paid, as well as royalties starting at 26% (12/20) Human Genome Sciences Inc. (HGSI) CoGenesys* CoGenesys got rights to develop products based on certain HGS genes, and to albumin-fusion technology; it is being spun out of HGS HGS also is providing a $10M startup loan; HGS gets an up-front payment and would get a portion of any revenues; it also retains a right of first refusal to develop certain products that may be developed (12/13) 294 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Hyperion Biotechnology Inc.* IR BioSciences Holdings Inc. (OTC BB:IRBO) Hyperion will perform research on IR’s anthrax agent Viprovex Hyperion is working with IR subsidiary ImmuneRegen BioSciences in the deal; terms were not disclosed (10/20) IDM Pharma Inc. (IDMI) Pharmexa A/S (Denmark; CSE: PHARMX) IDM is selling Pharmexa assets related to its infectious disease programs IDM is getting $1 2M in cash and certain rights to use Padre and Epitope Identification System technologies that were included in the deal (1 1/25) Illumina Inc. (ILMN) PharmacoDesign* (South Korea) PharmacoDesign acquired a BeadStation system and genotyping arrays and reagents PharmacoDesign will genotype various Korean populations to study certain diseases; Illumina has rights to incorporate resulting biomarkers into SNP panels under an exclusive, royalty-bearing license (10/25) ImmunoGen Inc. (IMGN) Genentech Inc. (NYSE:DNA) Genentech got exclusive rights to use Tumor-Activated Prodrug technology with antibodies to an undisclosed target The deal marks Genentech’s fourth license to the technology; ImmunoGen gets a $1M license payment and could receive milestone and royalty payments (12/13) Ingenuity Systems Inc.* Genizon BioSciences Inc.* Genizon licensed the Ingenuity Pathways Analysis 3.0 system The application will be used to identify targets; terms were not disclosed (10/25) Innovata plc (UK; LSE:IOV) Serologicals Corp. (SERO) Serologicals subsidiary Celliance acquired ubiquitous chromatin opening element gene expression technology The technology is used in protein production; Innnovata previously said the technology was not core to its business; terms of the deal were not disclosed (10/3) Intercell AG (Austria; VSE:ICLL) Pelias Biomedical Development AG* (Austria) Pelias gained rights to certain antigens that target pathogens in hospital infections Intercell gets an up-front payment and would get royalties on sales; it also holds a major stake in Pelias, which it helped establish (12/9) InterMune Inc. (ITMN) Targanta Therapeutics Inc.* Targanta acquired oritavancin, an antibiotic that has completed two Phase III trials InterMune is entitled to $9M in up-front and milestone payments and got a promissory note worth up to $25 million; the note will convert into Targanta stock as objectives are reached (12/27) Isogenica Ltd.* (UK) Amgen Inc. (AMGN) Isogenica will use its CIS display technology to select peptide candidates to certain Amgen targets Isogenica will get research fees and could receive milestone and royalty payments on resulting products (1 1/7) Lexicon Genetics Inc. (LEXG) Genentech Inc. (NYSE:DNA) Lexicon will perform research on a number of targets from Genentech’s Secreted Protein Discovery Initiative program Lexicon is entitled to $25M in up-front, milestone and research funding during the three-year research phase; Lexicon also could receive development milestones and royalties on any sales or share in costs and profits (12/1) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 295 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Lexicon Genetics Inc. (LEXG) Taconic Farms Inc.* Deal for the marketing and licensing of certain knockout mice made by Lexicon Taconic will provide breeding services and licenses for more than 1,000 lines and distribute the knockout mice (1 1/1 1) Macrozyme BV* (the Netherlands) Genzyme Corp. (GENZ) Collaboration to explore Macrozyme’s small-molecule library as inhibitors of glucosylceramide synthase The initial focus is on diabetes and insulin resistance; Macrozyme will get research funding and could get milestone and royalty payments (1 1/24) Medisyn Technologies Inc.* Humanetics Corp.* Collaboration to develop natural, non-prescription compounds focused on disease prevention Medisyn will provide natural compounds; Humanetics will be responsible for clinical development; further terms were not disclosed (10/20) Memory Amgen Inc. Pharmaceuticals (AMGN) Corp. (MEMY) Collaboration to develop PDE10 inhibitors for indications including certain neurological and psychiatric disorders Memory gets an up-front payment of $5M and could get $5.1M in research funding over two years; it also is entitled to milestone and royalty payments (10/17) Micromet AG* (Germany) MedImmune Inc. (MEDI) They initiated a second program, against an undisclosed target antigen The companies are using Micromet’s BiTE platform in the drug discovery effort; terms were not disclosed (1 1/21) Migenix Inc. (Canada; TSE:MGI) Cutanea Life Sciences Inc.* Cutanea got rights to develop and market MX-594AN for a number of dermatological indications Migenix gets an up-front payment and up to $21M in development and sales milestones, as well as royalties on any sales; Phase II trials in acne have been completed (12/8) Mucosal Therapeutics LLC* Serenex Inc.* Serenex got worldwide rights to SNX-1012 for chemotherapyand radiation-induced oral mucositis Phase II trials on the product are being planned; terms of the license deal were not disclosed (10/6) MultiCell Technologies Inc. (OTC BB: MCET) Living Cell Technologies Ltd. (Australia; ASX:LCT) They formed a joint venture to develop therapeutic liver cell applications MultiCell will develop extended functionality of its adult liver stem cells and immortalized human hepatocytes using LCT’s encapsulation technology; they will co-own resulting products (10/4) NatImmune A/S* (Denmark) Enzon Pharmaceuticals Inc. (ENZN) Enzon licensed recombinant human mannan-binding lectin, a protein being developed to prevent severe infections NatImmune gets $10M up front and is entitled to milestone and royalty payments; NatImmune retains rights in the Nordic countries and has certain rights to develop topical formulations (10/3) 296 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) NicOx SA (France; Eurolist: NICOX) Topigen Pharmaceuticals Inc.* (Canada) Topigen got North American rights to NCX 1020, a Phase IIa drug for treating chronic obstructive pulmonary disease and other respiratory disorders NicOx gets €2M up front and up to €52.9M in milestone and commercial success fees, in addition to a share of future revenues; that total includes fees that could be received if Topigen exercises its option to get rights in the rest of the world (10/27) Novavax Inc. (NVAX) IGI Inc. (AMEX:IG) IGI extended for 10 years its exclusive license to use certain Novavax technologies IGI’s rights to the Novasome lipid vesicle encapsulation technology, micellar nanoparticles and the Ultrasponge technology cover a number of applications (12/13) OncoMab Acceptys Inc.* GmbH* (Germany) The companies combined their human antibody therapeutic pipelines and their R&D operations Acceptys got rights to evaluate, acquire and develop all eight lead antibody cancer candidates from the OncoMab pipeline, which will be jointly developed (12/23) OriGene Technologies Inc.* Cytomyx Holdings plc* (UK) Deal to co-develop tools to pro- Terms of the deal were not disclosed (10/17) file gene expression and biomarker validation in a range of cancers PIramed Ltd.* (UK) Genentech Inc. (NYSE:DNA) Collaboration to develop PIramed compounds targeting PI 3-kinase, an extracellular enzyme implicated in cancers PIramed gets an up-front payment and could receive up to $230M in milestone payments up through product approval, as well as research funding and royalties on any sales (1 1/30) Provid Palatin Pharmaceuticals Technologies Inc.* Inc. (AMEX:PTN) Research services deal under which Provid will optimize leads for Palatin Provid will use its technologies on drug candidates identified using Palatin’s MIDAS technology; terms were not disclosed (10/17) RheoGene Inc.* Serologicals got a semiexclusive license to RheoGene’s RheoSwitch System and related technologies Serologicals subsidiary Chemicon International Inc. got rights to use the technology in its research product lines focused on specialty research markets; terms were not disclosed (1 1/28) Rigel Serono SA Pharmaceuticals (Switzerland; Inc. (RIGL) NYSE:SRA) Serono got exclusive rights to develop and sell products from Rigel’s Aurora kinase inhibitor program; the license is worldwide except Japan Rigel gets a $10M license fee and a $15M equity investment at a premium up front; development and sales milestones could push the total value to $160M, plus royalties on any resulting sales (10/25) Savient Indevus Pharmaceuticals Pharmaceuticals Inc. (SVNTE) Inc. (IDEV) Indevus acquired Delatestryl, an injectable testosterone product approved for male hypogonadism Savient gets an initial payment of $5M and a portion of sales for three years; Indevus also will purchase about $1.9M of inventory (12/13) Serologicals Corp. (SERO) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 297 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) SD Adventrx Pharmaceuticals Pharmaceuticals Inc.* Inc. (AMEX:ANX) Adventrx got U.S. rights to ANX-530, an emulsion formulation of vinorelbine tartrate Vinorelbine is used in cancer treatments; Adventrx’s license includes all rights to future vinca alkaloid formulations (10/4) Sontra Medical Corp. (SONT) EpiVax Inc.* Collaboration to investigate the topical delivery of EpiVax’s therapeutic HIV vaccine and other DNA vaccines They will use Sontra’s SonoPrep ultrasonic skin permeation device in the effort; terms of the deal were not disclosed (10/20) Stem Cell Sciences plc (UK; AIM:STEM) Lexicon Genetics Inc. (LEXG) Lexicon gained increased rights to Internal Ribosome Entry Site technology for genetically modified mice SCS gets an up-front payment and will share revenues from sublicenses; it also got certain rights to Lexicon’s gene targeting technology for use in stem cell and progenitor cell lines (1 1/3) Stem Cell Sciences plc (UK; AIM:STEM) Serologicals Corp. (SERO) Deal to manufacture and market embryonic stem cell media for the research market Serologicals subsidiary Chemicon International Inc. got worldwide rights to make and market a fully formulated cell culture media (10/6) Telomolecular Corp.* New Life Scientific Inc. (OTC BB:NWLF) Collaboration to develop products that treat aging and age-related diseases They plan to explore potentially synergistic technologies in the deal, terms of which were not disclosed (12/6) Tranzyme Pharma Inc.* Open Biosystems Inc.* OBI licensed exclusive rights to human-based translentiviral gene expression technology OBI also will assume Tranzyme’s operations in Birmingham, Ala.; Tranzyme will get annual payments and royalties on any resulting sales (1 1/14) U.S. Biodefense Inc. (OTC BB: UBDE) AntiCancer Inc.* Collaboration to develop approaches for using human neural crest stem cells and their potential in transplantation The goal is to develop treatments in the area of central nervous system diseases; terms of the deal were not disclosed (10/18) VisiGen Biotechnologies Inc.* Applied Biosystems Group (NYSE:ABI) They entered a definitive agreement to collaborate on sequencing technologies Applied Biosystems intends to make an equity investment in VisiGen; terms were not disclosed (10/26) Xcyte Therapies Inc. (XCYT) Invitrogen Corp. (IVGN) Invitrogen is acquiring Xcyte’s T-cell expansion technology, known as the Xcellerate Process Xcyte gets $5M and a percentage of any sublicensing revenue; the deal includes data generated through various trials of the Xcellerated T Cells product (12/15) Xencor Inc.* Genentech Inc. (NYSE:DNA) Collaboration to use Xencor’s XmAb technology to develop drugs against the antibody targets CD20 and Her2, and an undisclosed antigen Xencor gets $5M up front and annual license fees, as well as potential milestone payments for each target and royalties on any sales; Genentech’s license is exclusive and worldwide (12/1) 298 Company* (Country; Symbol) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Company Deals With Other Biotechnology Companies: Collaborations, Agreements, Equity Participation (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Type/Product Area Terms/Details (Date) Xencor Inc.* MedImmune Inc. (MEDI) MedImmune got rights to XmAb engineered antibody Fc domains for creating antibody candidates against tumor targets Xencor gets an up-front payment and is eligible to receive additional commercial license fees, milestone payments and royalties on any sales (12/7) Xenogen Corp. (XGEN) Gene Logic Inc. (GLGC) Xenogen will produce and characterize lines of bioluminescent animal models for Gene Logic The deal follows an earlier agreement in which Gene Logic purchased Xenogen equipment and licensed biophotonic imaging technology (10/13) XOMA Ltd. (XOMA) Crucell NV (the Netherlands; CRXL) Crucell got expanded rights to XOMA’s bacterial cell expression technology The deal improved Crucell’s position to perform phage display for infectious diseases with third-party collaborators; terms were not disclosed (10/5) Notes: * Private companies are indicated with an asterisk. Unless otherwise notes, the trading symbols listed for public biotechnology companies are on the Nasdaq market. AIM = Alternative Investment Market; AMEX = American Stock Exchange; ASX = Australian Stock Exchange; CSE = Copenhagen Stock Exchange; FSE = Frankfurt Stock Exchange; HEX = Helsinki Stock Exchange; LSE = London Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; PK = Pink Sheets; SSE = Stockholm Stock Exchange; SWX = Swiss Stock Exchange; TSE = Toronto Stock Exchange; VSE = Vienna or Vancouver Stock Exchange. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 299 2005 Biotech-Biotech Collaborations: Modified And Terminated Agreements I. MODIFIED AGREEMENTS Company* (Country; Symbol) Company* (Country; Symbol) Change from original agreement Terms/Details (Date) Cellegy ProStrakan Pharmaceuticals Group plc Inc. (CLGY) (UK; LSE:PSK) They renegotiated deal under which ProStrakan distributes Rectogesic in Europe ProStrakan will assume support responsibility, and purchase product directly from the manufacturer; Cellegy gets $2M and up to $0.75M in milestone payments (1 1/10) Curis Inc. (CRIS) Genentech Inc. (NYSE:DNA) They amended June 2003 deal to extend Genentech’s funding of the development collaboration in cancer Genentech is providing $2M to extend the Hedgehog-inhibition program, which was set to expire in June 2005, another six months, with a six-month option (4/14) Cytomedix Inc. (OTC BB:CYME) Harvest Technologies Inc.* They resolved litigation related to Cytomedix’s platelet gel technology A license has been granted to Harvest as part of the settlement; further terms were not disclosed (5/24) IDM Pharma Inc. (IDMI) Innogenetics NV (Belgium; Euronext:INNX) They extended for six months a collaboration to develop vaccines for viral diseases The extension through March 2006 is intended to enable Innogenetics to generate clinical candidates; IDM is entitled to milestone and royalty payments (10/3) Lexicon Genetics Inc. (LEXG) Deltagen Inc. (PK:DGENQ) They settled Lexicon’s claim in Deltagen’s bankruptcy proceedings and agreed on Deltagen’s assumption of a sublicense deal from Lexicon Lexicon received $4M in the settlement and could get up to $6M more from Deltagen’s licensing revenues from existing lines of knockout mice; Lexicon also is entitled to royalty payments (3/31) Mergen Ltd.* Oxford Gene Technology Ltd.* (UK) Agreement resolving patent infringement litigation between the companies Mergen has obtained a license from OGT for its expression chips in the U.S., Europe and Japan, allowing it to make and sell microarrays (1/20) ML Laboratories Maxygen Inc. plc (UK; LSE:MLB) (MAXY) Maxygen gained expanded rights to Ubiquitous Chromatin Opening Element technology Maxygen expanded its license from use in research to use in development of therapeutic proteins; terms were not disclosed (6/20) NiKem Research Srl* (Italy) They expanded and extended a research services agreement NiKem will continue to provide medicinal chemistry services to optimize inhibitors of ubiquitin-specific proteases for use as cancer agents (5/9) FIRST QUARTER 300 Hybrigenics SA* (France) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech-Biotech Collaborations: Modified And Terminated Agreements (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Change from original agreement Terms/Details (Date) Perfusion Partners and Associates Inc.* Cytomedix Inc. (AMEX:GTF) They settled a patent dispute over platelet-derived therapies for treating wounds and other damaged tissue Perfusion and affiliate Transcorporeal Inc. got a license to Cytomedix technology and will pay royalties of $250,000 and 10% of future sales (6/27) Transgenomic Inc. (TBIO) Geron Corp. (GERN) Transgenomic will provide additional modified nucleic acid-building block compounds to Geron The deal is an addendum to an existing master supply agreement between the companies; terms were not disclosed (4/20) XOMA Ltd. (XOMA) Genentech Inc. (NYSE:DNA) They restructured terms of their deal covering Raptiva, which is approved for treating plaque psoriasis XOMA opted to take a mid-single-digit royalty on sales and won’t be responsible for funding any development or marketing activities; XOMA no longer is obliged to repay a $40M development loan (1/12) II. TERMINATED AGREEMENTS Inex Enzon Pharmaceuticals Pharmaceuticals Corp. (Canada; Inc. (ENZN) TSE:IEX) Enzon is ending deal to develop Inex’s cancer product Marqibo The product, vincristine sulfate liposomes injection, received a not-approvable letter from the FDA in January calling for more trials; Inex is due $5M under the deal (3/17) Micromet AG* (Germany) Enzon Pharmaceuticals Inc. (ENZN) They ended a deal to identify and develop antibody-based drugs for treating inflammatory and autoimmune diseases They had combined technology in singlechain antibodies in the April 2002 collaboration; Micromet gets rights to the lead candidate (MT203) generated in the deal, and Enzon would get royalties; crosslicense and marketing agreements between the companies remained unchanged (1 1/28) XOMA Ltd. (XOMA) Zephyr Sciences Inc.* XOMA terminated a 2004 deal under which Zephyr gained rights to bactericidal/permeability-increasing proteinrelated products XOMA said Zephyr did not meet the financing requirements of the deal, which included the lead product Neuprex; the deal called for $1 1M in license fees and up to $62M in milestone payments, as well as royalties on any sales (7/15) Notes: * Private companies are indicated with an asterisk. Unless otherwise noted, stock symbols listed are on the Nasdaq market. AMEX = American Stock Exchange; LSE = London Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-theCounter Bulletin Board; PK = Pink Sheets. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 301 2005 Manufacturing, Marketing And Distribution Agreements Between Biotechnology Companies Company* (Country; Symbol) Company* (Country; Symbol) Product Terms/Details (Date) FIRST QUARTER Agencourt Bioscience Corp.* Amplicon Express Inc.* Alliance to co-market a suite of BAC library construction and sequencing services Each will provide technology to the effort focused on bacteria artificial chromosomes, which are vectors designed to clone DNA fragments (3/21) Ambion Diagnostics (unit of Ambion Inc.*) AcroMetrix Corp.* AcroMetrix will manufacture Armored RNA-based products and distribute them to laboratories and manufacturers Ambion will supply AcroMetrix custom products based on the Armored RNA technology for further development; terms were not disclosed (3/16) Argenta Discovery Ltd.* (UK) TTP LabTech Ltd.* (UK) They launched a high-content assay development and screening service The offering for drug discovery will be promoted by both companies (1/24) ArtisOptimus Inc.* Taconic Farms Inc.* Deal to bring a collection of primary mouse embryonic fibroblasts to the research community ArtisOptimus will produce and distribute MEFs made from knockout mouse models to which Taconic holds exclusive rights; ArtisOptimus also licensed specific models (2/9) BioBalance Corp. (OTC BB: BBAL) Benchmark Biolabs Inc.* Benchmark will manufacture ProBactrix for clinical trials The product is a live strain of E. coli M-17 being developed for gastrointestinal disorders; terms were not disclosed (3/14) Cobra Biomanufacturing plc (UK; LSE:CBF) Oncolytics Biotech Inc. (Canada; ONCY) Extended deal under which Cobra will manufacture and supply Reolysin The manufacturing deal on the human reovirus-based product is worth more than $1.4M to Cobra in 2005 (2/8) EDC Biosystems Inc.* Aurora Discovery Inc.* Deal to co-market EDC’s acoustic liquid-handling instrumentation and Aurora’s ChemLib microplates Terms of the deal were not disclosed (3/21) Halozyme Therapeutics Inc. (AMEX:HTI) Peregrine Pharmaceuticals Inc. (PPHM) Deal for the manufacture of a Halozyme recombinant human enzyme, which will be used in its Cumulase and Enhanze SC producs The manufacturing will be performed by Peregrine subsidiary Avid Bioservices Inc.; terms of the deal were not disclosed (2/17) Hawaii Biotech Inc.* Cobra Biomanufacturing plc (UK;LSE:CBF) Cobra will manufacture materials for clinical trials of vaccines against dengue fever and West Nile disease Terms of the deal were not disclosed; trials of the recombinant subunit vaccine candidates are expected to begin in 2006 (3/2) 302 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology Companies (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Product Terms/Details (Date) LION Bioscience AG (Germany; FSE:LIOG) BioBase GmbH* (Germany) Collaboration to integrate BioBase’s network content into LION’s software products Terms of the deal were not disclosed (2/10) Quantum Dot Corp.* Chemicon International (subsidiary of Serologicals Corp.; SERO) Chemicon got rights to market specific quantum dot-containing products for detecting antibody-antigen interactions in immunological experiments The deal adds secondary antibody detection technologies to Chemicon’s general reagents product portfolio; terms were not disclosed (3/4) Stratagene Corp. (STGN) Affymetrix Inc. (AFFX) Stratagene will provide Affymetrix customers with new software solutions for GeneChip data analysis Stratagene will develop a statistical analysis solution of Affymetrix gene expression microarrays under the nonexclusive deal (2/7) Albany Molecular will manufacture the drug-linker system used in Seattle Genetics’ SGN-35 product Clinical trials of the antibody-drug conjugate are expected to begin in 2006; the deal also provides licensees of Seattle Genetics’ ADC technology to work directly with Albany Molecular to obtain drug-linkers for their own trials (5/5) SECOND QUARTER Albany Molecular Research Inc. (AMRI) Seattle Genetics Inc. (SGEN) Ambion Inc.* Kreatech Kreatech will use Ambion Biotechnology BV* technology in development (the Netherlands) of a solution for gene expression analysis Ambion will provide its MessageAmp II a RNA amplification system under the supply agreement, terms of which were not disclosed (6/27) Ardana plc (UK; LSE:ARA) Cytochemia AG* (Germany) Cytochemia got exclusive rights to market Striant SR in Germany Striant SR is a mucoadhesive buccal testosterone treatment for hypogonadism; Ardana gets an up-front payment and ongoing suppy revenues (6/16) Auxilium Oscient Pharmaceuticals Pharmaceuticals Inc. (AUXL) Corp. (OSCI) Two-year deal to co-promote Auxilium’s marketed product Testim in the U.S. for treating hypogonadism Oscient will promote Testim to primary care physicians, and share profits from those sales above a pre-determined baseline (4/13) Biogen Idec Inc. (BIIB) Genentech Inc. (NYSE:DNA) Genentech is purchasing Biogen Idec’s biologics manufacturing facility in Oceanside, Calif. Genentech will pay about $408M in cash for the facility and is expected to offer jobs to the 403 employees at the facility (6/16) Biomedical Frontiers Inc.* Hemosol Corp. (Canada; HMSL) Hemosol will produce the iron-binding drugs 40SD02 and 25SD04 for Biomedical The injectable drug formulations will be used for preclinical and clinical studies in iron poisoning, iron overload and diabetic complications; terms were not disclosed (4/4) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 303 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology Companies (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Product Terms/Details (Date) BioReliance Corp. (subsidiary of Invitrogen Corp.; IVGN) Acambis plc (UK; ACAM) Acambis acquired a U.S.based fill/finish facility, where it will manufacture vaccines BioReliance gets $3M up front and another $4.5M over 12 years; Acambis will assume responsibility for the 12-year lease (5/9) Capital Genomix Inc.* SpectruMedix LLC* Worldwide deal to market and sell the GeneSystem320 for capillary electrophoresisbased applications. The companies intend to launch the product in 3Q:05; terms were not disclosed (5/4) Cobra Biomanufacturing plc (UK; LSE:CBF) Synco BioPartners* (the Netherlands) Collaboration to manufacture plasmid DNA for Phase III trials and commercial supply Synco licensed rights related to the pDNA manufacturing process; they also will work together on marketing of their pDNA manufacturing services (5/4) Gene Bridges GmbH* (Germany) Covalys Biosciences AG* (Switzerland) Deal to develop DNA engineering kits to generate SNAP-tag fusion proteins The work is based on Gene Bridges’ Red/ET recombination technology; the cloning kits are expected to be on the market in 3Q:05 (6/14) Inte:Ligand GmbH* (Austria) Molecular Networks* (Germany) Deal to integrate Molecular Networks’ Corina technology into Inte:Ligand’s Ilib Diverse platform Ilib Diverse is a virtual compound librarygeneration platform; they also plan to share complementary technologies in the future (4/26) Invitrogen Corp. (IVGN) Applied Biosystems Group (NYSE:ABI) Co-marketng deal to sell a combined collection of labeling technologies The products include ABI’s iTRAQ and ICAT reagents and Invitrogen’s SILAC technology; ABI also will provide software support for SILAC; terms were not disclosed (6/6) Inyx Inc. (OTC BB:IYXI) Kos Pharmaceuticals Inc. (KOSP) 10-year deal under which Inyx will produce Kos’ Azmacort Inhalation Aerosol product line Inyx said the deal is expected to generate about $10M in annual revenues (4/15) Lorantis Ltd.* (UK) Althea Technologies Inc.* Althea will manufacture the protein component of Lorantis’ HepVax, a hepatitis B therapeutic vaccine Althea will provide a range of services under the contract as the product advances toward clinical evaluation; terms were not disclosed (4/27) Luminex Corp. (LMNX) EraGen Biosciences Inc.* The companies entered an expanded licensing and distribution agreement EraGen got rights to sell Luminex 100 Systems and kits that include nonstandard nucleic acid bases, proprietary to EraGen, designed for certain in vitro clinical diagnostic purposes (4/26) Omnia Biologics Inc.* AT-GC BioPharm Inc.* Deal to develop AT-GC Electronic Eye technology for the manufacture of biopharmaceuticals They will work together to provide the technology under undisclosed terms (3/24) 304 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology Companies (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Product Terms/Details (Date) Primus CollaGenex Pharmaceuticals Pharmaceuticals Inc.* Inc. (CGPI) Deal under which CollaGenex will promote Alcortin and Novacort to dermatologists in the U.S. Alcotrin is a topical antifungal steroid combination; Novacort is a topical steroid and anesthetic; terms of the deal were not disclosed (6/8) Procognia Ltd.* (UK) Qiagen NV (the Netherlands; QGEN) Qiagen got exclusive rights to market Procognia’s “on-chip” protein glycoanalysis technology The products will be combined with Qiagen’s QProteome product line; terms of the deal were not disclosed (5/16) Protein Sciences Corp.* ViRexx Medical Corp. (Canada; TSE:VIR) Deal under which PSC will manufacture ViRexx’s lead Chimigen vaccine, HepaVaxx B Phase I trials of the hepatitis B vaccine are expected to begin in 3Q:05; terms of the deal were not disclosed (4/28) Proteos Inc.* DNAPrint Genomics Inc. (OTC BB:DNAP) Proteos will manufacture DNAP’s PT-401 (Super EPO dimer) for preclinical testing Terms of the deal were not disclosed (5/14) StemCo Biomedical Inc.* StemCell Technologies* (Canada) Worldwide deal under which StemCell will distribute StemCo’s Aldefluor product Aldefluor is a kit that enables the identification of stem and progenitor cells; StemCell previously had rights only in the Americas and much of the Asia-Pacific region (6/9) Tm Bioscience Corp. (Canada; TSE:TMC) InterGenetics Inc.* Tm will supply custom Tag-It reagents to InterGenetics for OncoVue under a five-year deal InterGenetics is expected to buy at least $7.5M in reagents over the five years; Oncovue is a genetic-based breast cancer risk test (6/30) THIRD QUARTER Benitec Ltd. (Australia; ASX:BLT) Promega Corp.* Promega will hold a worldwide nonexclusive license to make and sell DNA-directed RNAibased research products Promega will receive a cash payment and continued royalties from certain sublicenses; the agreement is part of a settled contract dispute (8/22) Biophage Pharma Inc. (Canada; TSE:BUG) Integrated Environmental Technologies Ltd. (OTC BB:IEVM) Deal under which each company can market a pathogen detection and control system The combined marketing effort will promote IET’s EcaFlo equipment and Biophage’s PDS Biosensor technology (9/23) Cobra Biomanufacturing plc (UK; AIM:CBF) Auxilium Pharmaceuticals Inc. (AUXL) Cobra will manufacture and supply AA4500 for Phase II/III trials Auxilium is developing the protein drug for Peyronie’s disease and Dupuytren’s disease; the value of the deal exceeds $3.3M through 2006 (8/2) GTC Biotherapeutics Inc. (GTCB) Merrimack Pharmaceuticals Inc.* Deal for the further production of Merrimack’s MM-093 by GTC The product is a recombinant version of human alpha-fetoprotein in Phase II trials for rheumatoid arthritis; terms were not disclosed (9/20) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 305 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology Companies (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Product Terms/Details (Date) JPT Peptide Quality Technologies Biological Inc.* GmbH* (Germany) Nonexclusive deal under which QBI will distribute JPT’s peptide-based products in America JPT is a wholly owned subsidiary of Jerini AG; terms of the deal were not disclosed (9/15) Large Scale Biology Corp. (LSBC) Planet Biotechnology Inc.* They expanded a deal to extract and purify Planet’s CaroRx The deal expands on a July 2004 agreemment covering the plant-made antibody; terms were not disclosed (7/12) Nonlinear Dynamics Ltd.* (UK) Invitrogen Corp. (IVGN) Invitrogen will promote and distribute life science analysis software from Nonlinear The deal covers a number of products; terms were not disclosed (8/29) Omnia Biologics Inc.* Lentigen Corp.* Omnia will provide Lentigen access to its cGMP facilities and services The deal focuses on development of Omnia’s Lentiviral vector gene delivery technology; terms were not disclosed (8/17) Omnia Biologics Inc.* AFG Biosolutions Inc.* Omnia will provide AFG with manufacturing and product development services. AFG works on products against potential biological weapons; details on the deal were not disclosed (7/19) Progenitor Cell Therapy LLC* Cellerant Therapeutics Inc.* Progenitor will manufacture Cellerant’s CLT-001 CLT-001 is a purified hematopoietic stem cell product being developed for various diseases; terms were not disclosed (9/13) Verus Paladin Labs Pharmaceuticals Inc. (Canada; Inc.* TSE:PLB) Deal to commercialize Twinject in Canada The product is an epinephrine auto-injector approved in Canada for emergency treatment of severe allergic reactions; terms of the deal were not disclosed (7/27) Wave Biotech LLC* Novavax Inc. (NVAX) Collaboration to develop a commercial-scale production process for Novavax’s avian flu vaccine and other products They will use Wave’s disposable cell culture technology in the effort; terms of the deal were not disclosed (9/13) XOMA Ltd. (XOMA) Cubist Pharmaceuticals Inc. (CBST) Deal to develop new processes to manufacture the twoantibody biologic HepeX-B for Phase III trials XOMA will develop processes for the manufacture of the two monoclonal antibodies in the hepatitis B product; longer-term and commerical deals are contemplated (9/20) Manufacturing and marketing deal relating to Acambis’ ChimeriVax-JE vaccine against Japanese encephalitis Bharat will be responsible for end-stage fill/finish processing and would market the vaccine in India and neighboring countries; terms were not disclosed (1 1/8) FOURTH QUARTER Acambis plc (UK; ACAM) 306 Bharat Biotech International Ltd.* (India) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology Companies (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Product Terms/Details (Date) Amarillo Biosciences Inc. (OTC BB:AMAR) Global Kinetics Inc.* Global Kinetics will market ABI’s low-dose oral interferon product in Cambodia, Laos and Vietnam The product will be marketed for influenza indications; terms of the deal were not disclosed (10/20) Cell Genesys Inc. (CEGE) Genzyme Corp. (GENZ) Genzyme acquired Cell Genesys’ manufacturing operation in San Diego to support its gene therapy programs Cell Genesys gets $3.2M in cash in the deal; most of the approximately 40 employees have become Genzyme employees (1 1/22) Cobra Biomanufacturing plc (UK; AIM:CBF) Advaxis Inc. (OTC BB:ADXS) Cobra will manufacture experimental and commercial supplies of Advaxis’ Listeria cancer vaccines The deal supersedes a prior agreement; the initial product will be the Lovaxin C vaccine; terms of the deal were not disclosed (1 1/7) CombiMatrix Group (CBMX) CyGenics Ltd. (Australia; ASX:CYN) Nonexclusive deal for the distribution of CombiMatrix products and services CyGenics subsidiary Cell Sciences Pte. Ltd. will sell CustomArrays and CatalogArrays in Singapore, Malaysia, Thailand, the Philippines, Hong Kong and Indonesia (1 1/30) CombiMatrix Group (CBMX) Novavax Inc. (NVAX) Collaboration to develop an improved process for producing Novavax’s H5N1 bird flu vaccine They will use CombiMatrix’s technique for in-process monitoring of vaccine production in the effort, terms of which were not disclosed (1 1/9) Dendritic Nanotechnologies Inc. * Lumera Corp. (LMRA) Deal to develop surface chemistries suitable for applications on Lumera’s label-free array reader The deal focuses on Lumera’s ProteomicProcessor product; terms were not disclosed (1 1/10) Geneva Bioinformatics SA* (Switzerland) Genedata AG* (Switzerland) Deal under which they will integrate technologies for analyzing proteomics data The effort will integrate the Genedata Expressionist solution with the Melanie/ ImageMaster 2D Platinum solution (10/26) Gen-Probe Inc. (GPRO) Molecular Profiling Institute Inc.* Deal to accelerate development of cancer diagnostic products from Gen-Probe Molecular Profiling will help validate and commercialize up to four products, and provide certain contract research services; Gen-Probe acquired a minority interest in Molecular Profiling (10/26) GenTel BioSurfaces Inc.* Abnova Corp.* (Taiwan) Deal to develop custom multiplex immunoassays GenTel’s PATH Protein Microarray System will be used in the effort; terms of the deal were not disclosed (1 1/9) Nonlinear Dynamics Ltd.* (UK) Genedata AG* (Switzerland) Co-marketing deal to promote synergies between their Progenesis and Expressionist solutions The solution will be used to generate data in proteomics research; terms of the deal were not disclosed (10/20) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 307 2005 Manufacturing, Marketing And DIstribution Agreements Between Biotechnology Companies (Continued) Company* (Country; Symbol) Company* (Country; Symbol) Product Terms/Details (Date) Omnia Biologics Inc.* Lentigen Inc.* Nonexclusive deal regarding the manufacturing of clinicaland research-grade lentiviral vectors Each may refer clients to the other party for its respective services; additional terms were not disclosed (12/6) Peregrine Undisclosed Pharmaceuticals company Inc. (PPHM) Peregrine will provide development services and clinical supply manufacturing of a monoclonal antibody The antibody is in Phase II trials; the work will be done by Peregrine subsidiary Avid Bioservices Inc. (10/20) Pluristem Life Systems Inc. (Israel; OTC BB:PLRS) Biological Industries Ltd.* (Israel) Deal for the global distribution of joint serum-free media products designed for hematopoietic and mesenchymal stem cells They will use Pluristem’s PluriX bioreactor in the effort; Pluristem gets a license fee equal to 5% of sales of serum-free media for seven years (10/20) Solvo Biotechnologies Inc.* (Hungary) In Vitro Technologies Inc.* IVT will distribute Solvo’s in vitro ABC membrane transporter assay product line in the U.S. and Canada Terms of the deal were not disclosed (10/24) Strand Life Sciences Pvt. Ltd.* (India) Stratagene Corp. (STGN) Deal to develop a suite of next-generation bioinformatics software tools Stratagene will exclusively market resulting products, which will use Strand’s Avadis technology (12/8) Third Wave Technologies Inc. (TWTI) Genzyme Corp. (GENZ) They formed a preferred marketing agreement for Third Wave’s Invader UGT1A1 Molecular Assay Genzyme Genetics will provide testing for colorectal cancer patients in North America who may or are taking the cancer drug Camptosar; terms were not disclosed (10/27) Three Rivers Samaritan Pharmaceuticals Pharmaceuticals LLC* Inc. (AMEX:LIV) Samaritan got rights to distribute the amphotericin B product Amphocil in Greece and Cyprus Amphocil is indicated for the treatment of invasive aspergillosis; terms of the deal were not disclosed (12/14) Transgene SA (France; Eurolist: FR0005175080) Innogenetics NV (Belgium; Euronext:INNX) Transgene will manufacture Innogenetics’ hepatitis B therapeutic vaccine candidate The vaccine construct was developed by Transgene under a previous service agreement; terms were not disclosed (10/13) Tripos Inc. (TRPS) InforSense Ltd.* (UK) Companies will integrate drug discovery platforms Terms of the deal were not disclosed (12/12) Notes: * Private companies are indicated with an asterisk. Unless otherwise noted, stock symbols listed are on the Nasdaq market. AIM = Alternative Investment Market; AMEX = American Stock Exchange; ASX = Australian Stock Exchange; FSE = Frankfurt Stock Exchange; LSE = London Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; TSE = Toronto Stock Exchange. 308 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech Miscellaneous Collaborations Company* (Country; Symbol) Company (Country) Type/Product Area Terms/Details (Date) FIRST QUARTER Geneva Bioinformatics SA* (Switzerland) Current Science Group (UK) They formed a joint venture company named Current BioData Ltd. The new company will focus on the further development and marketing of GeneBio’s ProXenter discovery platform (3/3) NuGEN Technologies Inc.* MediBIC Inc.* (Japan) MediBIC will support the adoption of NuGEN’s Ovation family of RNA amplification systems in Asia Terms of the deal were not disclosed (2/1) Phenomenome Discoveries Inc.* PrecisionMed Inc. Collaboration to develop diagnostics for Alzheimer’s disease and bipolar disorder The effort will combine PrecisionMed’s clinical samples and information and PDI’s discovery and testing platform (2/4) Artemis Taconic Farms Pharmaceuticals Inc. GmbH (Germany; subsidiary of Exelixis Inc.; EXEL) Alliance for the generation and marketing of genetically engineered mice The deal combines Artemis’ leading technology in mouse genetics and genomics with Taconic’s expertise in rodents; terms of the deal were not disclosed (6/20) Avant ImmunoTherapeutics Inc. (AVAN) Paul Royalty Fund II LP Paul Royalty purchased an interest in royalties Avant will receive from sales of Rotarix by GlaxoSmithKline plc Avant gets $10M and would get $40M upon product launch in Europe and about $10M upon launch in the U.S.; Avant also retained an interest in royalties from the product, which is used against rotavirus infections (5/18) Diversa Corp. (DVSA) Bio Integration Technology Inc. (China) Collaboration to identify opportunities for Diversa’s enzyme products in the Chinese oil and gas industry Terms of the deal were not disclosed (4/25) Diversa Corp. (DVSA) Cargill Health and Food Technologies Collaboration to develop enzymes for the cost-effective production of an undisclosed product Diversa gets up-front payments and research funding, and is entitled to milestone payments, license fees and royalties on resulting products (4/1 1) Genaissance will provide pharmacogenetic clinical development services to clients of INC INC is a contract research organization; terms of the deal were not disclosed (6/7) SECOND QUARTER Genaissance INC Research Pharmaceuticals Inc. (GNSC) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 309 2005 Biotech Miscellaneous Collaborations (Continued) Company* (Country; Symbol) Company (Country) Type/Product Area Terms/Details (Date) Geneva Bioinformatics SA* (Switzerland) KOOPrime Pte. Ltd. (Singapore) KOOPrime will distribute GeneBio’s Phenyx software platform in Singapore, Malaysia, China and Taiwan The platform is used to identify and characterize proteins and peptides from mass spectrometry data; terms of the deal were not disclosed (6/22) Geneva Bioinformatics SA* (Switzerland) Hitachi Software Enginerring Co. Ltd. (Japan) Hitachi will distribute GeneBio’s Phenyx software platform in the Japanese market The platform is used to identify and characterize proteins and peptides from mass spectrometry data; terms of the deal were not disclosed (6/2) LineaGen Research Corp.* and the University of Utah Health Sciences Center IBM Collaboration to create a clinical genomics infrastructure designed to accelerate the molecular understanding of complex diseases IBM initally will intgrate Utah population databases into its Clinical Genomics Solution; future phases will center on development of tools to support molecular models of genetic disease (5/18) Palatin Technologies Inc. (AMEX:PTN) Competitive Technologies Inc. (AMEX:CTT) They settled a dispute on a license agreement regarding certain peptides for treating sexual dysfunction The technology-transfer company gets $1.7M in cash and 170,000 Palatin shares; Palatin and partner King Pharmaceuticals Inc. retain all rights to PT-141 (6/23) PharmaFrontiers INC Corp. (OTC BB: Research Inc.* PFTR) Deal under which INC will manage PharmaFrontiers’ multiple sclerosis development program INC is a contract research organization; PharmaFrontiers’ MS product Tovaxin is moving into Phase II trials; terms of the deal were not disclosed (5/3) Senomyx Inc. (SNMX) Kraft Foods Global Inc. They extended the research phase of their collaboration to discover flavor modifiers in the dessert category The deal was extended to July 30, 2005; Senomyx gets research funding and is entitled to royalties on any resulting sales (5/2) Senomyx Inc. (SNMX) Nestle SA (Switzerland) They extended for three years a deal to discover novel flavors and flavor enhancers in the dehydrated and culinary food and frozen food fields The initial three-year deal was signed in 2002; Senomyx will get funding of up to $6.6M in the extension and would get royalties on any resulting sales (4/20) Spectrum Robert E. Bases Pharmaceuticals Inc. (SPPI) Spectrum acquired rights to lucanthone, a radiation sensitizer in Phase II trials Bases is inventor of a method of treating cancer of the central nervous system through the administration of lucanthone and radiation; terms were not disclosed (5/17) Vion B&P Co. Inc. Pharmaceuticals Inc. (VION) B&P got nonexclusive rights to use Vion’s Melasyn technology B&P plans to develop cosmetic products incorporating Melasyn, a synthetic form of melanin; Vion would get royalties on sales in countries where it has patents (4/15) Xenogen Corp. (XGEN) MIR purchased and sublicensed Xenogen’s biophotonic imaging technologies The contract research organization got rights to use the technology in preclinical research except in infectious diseases (4/12) 310 MIR Preclinical Services BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotech Miscellaneous Collaborations (Continued) Company* (Country; Symbol) Company (Country) Type/Product Area Terms/Details (Date) THIRD QUARTER Neurobiological Technologies Inc. (NTII) Celtic Pharma Holdings LP (Bermuda) Celtic, an equity firm, got rights to Xercept, a product in Phase III trials for swelling associated with brain tumors NTI gets $33 million in up-front payments and up to $15M more if regulatory objectives are reached; it would have a profitsharing arrangement in the U.S. and get royalties on sales outside the U.S. (9/20) NewGen Technologies Inc. (OTC BB: NWGN) Advanced Biotechnology Inc. They formed a joint venture to build and operate biodiesel plants in the Southeast The venture between NewGen subsidiary ReFuel America Inc. and ABI will be named Advanced Biotechnologies LLC; terms were not disclosed (9/14) Novavax Inc. (NVAX) Pharmelle LLC Novavax sold the non-core products AVC Cream, NovaNatal and NovaStart to Pharmelle Novavax got $2.5M and would get royalty payments if product sales exceed certain levels (9/23) Senomyx Inc. (SNMX) Kraft Foods Global Inc. They extended for two years a deal on flavor modifiers for a dessert product category and on an existing food and beverage product field Senomyx gets discovery and development funding of $2.7M over the two-year extension period and would get royalty payments on any resulting sales (7/29) Senomyx Inc. (SNMX) Cadbury Adams USA LLC Deal for the discovery of new flavor ingredients in the gum confectionary area Senomyx gets research funding and is entitled to milestone and royalty payments in the deal (7/18) FOURTH QUARTER Amarillo Biosciences Inc. (OTC BB:AMAR) Gesellschaft Fur Medizinisch and Technische Investionen mbH & CoKG (Germany) Amarillo entered a deal with Curtis Martin, CEO of the German venture capital firm, for commercialization of low-dose oral interferon GMTI will work to commercialize the product in Thailand, Brunei, Myanmar, the Philippines, Malaysia, Singapore and Indonesia; terms were not disclosed (1 1/30) ChondroGene Ltd. (Canada; CDNX:CDG) Kaiser Permanente Deal to develop a research database infrastructure for use in genomic research The principal objective of the database is to standardize and achieve consistency in the format of data for future studies; terms were not disclosed (10/28) IT-omics* (France) OmniViz Inc.* Deal to integrate software for use in the drug discovery process Terms of the deal were not disclosed; OmniViz focuses on visual informatics software (1 1/29) Notes: * Private companies are indicated with an asterisk. Unless otherwise noted, the trading symbols listed for public companies are on the Nasdaq market. AMEX = American Stock Exchange; CDNX = Canadian Venture Exchange; OTC BB = Over-the-Counter Bulletin Board. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 311 2005 Collaborations Between Biotechnology Companies and Universities/Nonprofit Institutions Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Adherex Technologies Inc. (AMEX:ADH) National Cancer Institute Level III collaboration For clinical development of the company’s lead compound, ADH-1 (Exherin) Following additional preclinical work, they will negotiate a Cooperative Research and Development Agreement under which the NCI would sponsor trials (3/1 1) Affymetrix Inc. (AFFX) Harvard Medical School Agreement Harvard gets early access to nextgeneration GeneChip human mapping microarrays The Partners HealthCare Center for Genetics and Genomics at Harvard will examine patient samples to research the genetic origins of atherosclerosis (2/16) Affymetrix Inc. (AFFX) Karolinska Institutet (Sweden) Alliance Five-year deal to accellerate the translation of basic genetic research into tools to improve health care Disease areas include atherosclerosis, breast cancer, rheumatoid arthritis, asthma and dyslexia; the institute is part of the Affymetrix Translational Medicine Initiative (2/8) Affymetrix Inc. (AFFX) Institut Curie (France) Alliance They will use GeneChip microarray technology in clinical trials to produce genetic signatures for cancer The institute will conduct the studies; the goal is to develop diagnostic tests, initally for prognosis of breast and eye cancers; terms were not disclosed (2/2) Applied Biosystems (NYSE:ABI) National Center for Toxicological Research of the FDA Collaboration Applied Biosystems will help investigate toxicity of diabetes drugs The company will use its Expression Array System and Rat Genome Survey Microarray on samples provided by the FDA/ NCTR; terms were not disclosed (3/9) Applied Biosystems (NYSE:ABI) Stanford University and University of Miami Collaboration expansion They will continue studying genetic biomarkers associated with response in diffuse large B-cell lymphoma They also will begin studies to assess the predictive value of six genes on a certain chemotherapy regimen (1/10) Ardana Bioscience Ltd. (UK; LSE:ARA) UK Medical Research Council Agreement extension Deal made in 2000 was extended for three years Ardana gets rights to certain areas of the MRC’s Human Reproductive Sciences Unit, which would get cash payments if options are exercised (2/3) FIRST QUARTER 312 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) AVAX Technologies Inc. (OTC BB:AVXT) Presbyterian Medical Center Collaboration To conduct a trial of AVAX’s AC Vaccine in patients with nonsmall-cell lung cancer Presbyterian Medical Center and Hospital of the University of Pennsylvania will be exclusive partners and sites for the trial (2/22) Avidex Ltd.* (UK) Ludwig Institute for Cancer Research (Germany) Research collaboration Research will focus on immune effector molecules to NY-ESO-1expressing tumors The collaboration is based on an Avidex soluble monoclonal T-cell receptor that targets the antigen; terms were not disclosed (3/14) Aviva Systems Biology* University of California at San Diego License agreement Aviva got rights to Gene Regulation Elements Mapping and Analysis technology The technology is used to detect DNA fragments that interact with proteins; terms of the exclusive license were not disclosed (1/31) Benitec Ltd. (Australia; ASX:BLT) Garvan Institute of Medical Research (Australia) License agreement Benitec got rights to develop RNA-based drugs for diabetes, obesity and related disorders The work will focus on the c-Ccbl gene as a target; they also are discussing entering a collaboration in the area; terms were not disclosed (2/3) Biokine Therapeutics Inc.* (Israel) University of Kyoto (Japan) Product acquisition Biokine purchased all rights to T-140, a CXCR4 chemokine receptor antagonist The product may have applications in inflammatory disorders, HIV and cancer; terms were not disclosed (3/1) BioLineRx Ltd. (Israel) Tel Aviv License University and agreement Bar Ilan University (both in Israel) BioLineRx licensed rights to BL-2010, a product for treating resistant cancer Terms of the deal were not disclosed (1/12) BioLineRx Ltd. (Israel) The Hebrew University (Israel) License agreement BioLineRx licensed BL-1050, an HIV therapeutic Terms of the deal were not disclosed (1/12) Bionomics Ltd. (Australia; ASX:BNO) Walter and Eliza Hall Institute (Australia) Collaboration Letter of intent for a drug discovery collaboration in the area of ion channels The goal is to identify new lead molecules for treating central nervous system disorders; terms were not disclosed (2/25) BioVeris Corp. (BIOV) National Research Council of Canada License agreement BioVeris got rights to vaccines candidates for group B streptococcus and B meningococcus vaccines BioVeris got worldwide rights to the vaccines, and will pay a royalty on sales, including a minimum $10,000 annual royalty that begins immediately (2/10) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 313 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) BioVeris Corp. (BIOV) Children’s Hospital & Research Center at Oakland License agremeent BioVeris got rights to a vaccine candidate for Neisseria meningitidis serogroup B BioVeris also will pay $800,000 over two years to sponsor research on the vaccine; BioVeris would pay up-front, milestone and royalty fees if it exercises its option (1/13) BioVeris Corp. (BIOV) Brooke Army Medical Center Collaborative Research & Development Agreement Deal to develop a BioVeris will be able to commerBioveris test for cialize tests identified under the detecting markers of two-year agreement (1/5) disease and progression Carrington Laboratories Inc. (CARN) Southern Research Institute Collaboration renewal They added one year to 2002 deal to develop drug-delivery technology based on the natural polymer GelSite The deal was made with Carrington subsidiary DelSite Biotechnologies Inc.; terms were not disclosed (2/15) CeMines Inc.* The Children’s Hospital of Denver Research project To improve the diagnosis and monitoring of childhood leukemia CeMines is sposoring the project, which is based on its Molecular FingerPrinting diagnostic process (1/27) ChemDiv Inc.* University of Maryland Collaboration Deal to discover drugs for treating breast cancer The university’s Greenebaum Cancer Center gets access to ChemDiv libraries; ChemDiv also will provide medicinal chemistry services (1/18) ChemGenex Pharmaceuticals Ltd. (Australia; ASX:CXS) University of Texas M.D. Anderson Cancer Center License agreement ChemGenex licensed an anticancer platinum agent, now named CXS299 The agent is believed to have enhanced activity against cells that have the wild-type p53 gene; terms were not disclosed (2/9) Ciphergen Biosystems Inc. (CIPH) Johns Hopkins University School of Medicine Collaboration renewal They are working to discover novel protein biomarkers in the field of cancer Ciphergen will continue to provide financial support, technical assistance and access to technology platforms; it has rights to resulting discoveries (3/17) Ciphergen Biosystems Inc. (CIPH) University of Texas M.D. Anderson Cancer Center Research and license agreement To use Ciphergen’s technologies to further research in ovarian cancer Ciphergen division Ciphergen Diagnostics plans to refine biomarkers for use in an ovarian cancer diagnostic test (2/15) Cryptome Pharmaceuticals Ltd. (Australia; ASX:CRP) University of Virginia License agreement Cryptome got an option to a class of protein-derived compounds with antiinflammatory action Crytome has 12 months to exercise the option; the lead product is CR014, designed to prevent leakage of fluid through blood vessel walls (2/22) 314 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Crucell NV (the Netherlands; CRXL) National Institutes of Health License agreement Crucell got exclusive rights to patents for use in recombinant vaccines against Ebola virus The patents cover vaccine components, such as Ebola antigens and vectors; terms of the deal were not disclosed (3/18) Diffusion Pharmaceuticals LLC* New Approaches to Brain Tumor Therapy consortium Agreement NABTT will test Diffusion’s trans sodium crocetinate as a radiation sensitizer NABTT will conduct Phase I and II clinical trials in two different patient populations (3/1) Emergent BioSolutions Inc.* Health Protection Agency (UK) Collaboration Two-year deal to develop vaccines to prevent botulism Emergent will spend at least $2M on the project and gets worldwide rights, except in the UK (1/14) Genaissance Pharmaceuticals Inc. (GNSC) Vanderbilt University License agreement Genaissance got rights to technology for screening patients for susceptibility to drug- induced cardiac arrhythmias The technology covers testing for the presence of a common polymorphism in KCNE1, a cardiac ion-channel gene; terms were not disclosed (1/26) GeneCopoeia Inc.* RZPD (German genome research center) Distribution deal RZPD will distribute certain GeneCopoeia products in Europe The deal includes GeneCopoeia’s seven sets of 1 6,000 human OmicsLink ORF expression clones; terms were not disclosed (2/9) Generex Emory University Collaborations Biotechnology and Imperial Corp. (Canada; GNBT) College of London Deal to develop a smallpox vaccine based on using modified peptide antigens to stimulate immunity Generex subsidiary Antigen Express will work with scientists at the universities; terms were not disclosed (2/10) Geron Corp. (GERN) Hong Kong University of Science and Technology Alliance They formed a company to use telomerase activation to restore function in certain aged or diseased tissues Geron and the university’s Biotechnology Research Corp. established TA Therapeutics Ltd. in Hong Kong; each owns 50% of the new company (3/2) GMP Companies Inc.* Mayo Medical Laboratories License agreement Mayo will use GMP technology for gene-based testing The deal was made with GMP Genetics Inc.; terms were not disclosed (1/27) Hemispherx Biopharma Inc. (AMEX:HEB) U.S. governmentsponsored laboratories Collaboration For further studies of Hemispherx’s Alferon N against avian infleunza Details of the work were not disclosed (2/7) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 315 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Icoria Inc. (ICOR) U.S. Army Edgewood Chemical Biological Center Cooperative Research and Development Agreement To identify and validate biomarkers associated with exposure to chemical warfare agents The deal runs through October; contingent on future funding, they may conduct additional studies and develop a prototype blood-based field assay (1/27) Ingenuity Systems Inc.* Erasmus University Medical Center (the Netherlands) License agreement The center licensed access to the Ingenuity Pathways Analysis software They also entered a collaboration to develop new algorithms, visualizations and practical applications in molecular and clinical diagnostics (3/23) Innovive Pharmaceuticals Inc.* Penn State University License agreement Innovive got worldwide rights for the use of opioid growth factor in oncology applications OGF, also known as (Met5)-enkephalin, will be developed under the name INNO-105; terms of the deal were not disclosed (3/17) Insmed Inc. (INSM) University of California at San Francisco Option agreement Insmed got an option to use IGF-1 receptor antagonists to treat prostate cancer Research on the compounds will complement an existing Insmed program; terms of the deal were not disclosed (3/17) Juvaris BioTherapeutics Inc.* International AIDS Vaccine Initiative Collaboration Deal to use Juvaris’ immunostimulant technology to screen HIV vaccine candidates IAVI investigators will test the technology with HIV antigens; terms of the deal were not disclosed (3/23) Large Scale Biology Corp. (LSBC) University of Utah Research Foundation Collaboration To identify biomarkers from maternal blood tests for the early diagnosis of pregnancyrelated complications and disorders LSBC subsidiary Predictive Diagnostics Inc. will analyze blood samples provided by UURF; terms of the deal were not disclosed (3/21) Lumera Corp. (LMRA) Institute for Systems Biology Collaboration To develop a highthroughput platform for proteomics research Terms of the deal were not disclosed (2/14) Medical Marketing International Group plc (UK; AIM:MMG) King’s College London License agreement Their joint venture, Viratis, licenced a hepatitis therapy that uses ribozyme technology Details of the deal were not disclosed (3/4) Medical Marketing International Group plc (UK; AIM:MMG) King’s College London and Queen Mary University License agreement Technology for autoimmune diseases was added to their Viratis joint venture MMI’s stake in Viratis will increase to 72% as it provides further development funding (2/3) 316 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Medicure Inc. (Canada; TSE:MPH) University of Manitoba and University of Ottawa Heart Institute (Canada) License agreements Medicure acquired rights to a technology platform focused on development of lipidlowering therapeutics Medicure and the researchers will advance the platform; Medicure gets worldwide rights (1/27) Metabolon Inc.* Massachusetts General Hospital Collaboration To discover biomarkers The work is being funded by a for diabetic nephropathy grant from the National Institute in Type I diabetes of Diabetes and Digestive and Kidney Diseases to Massachusetts General Hospital (3/29) Metabolon Inc.* High Q Foundation Collaboration They will perform a biomarker study for Huntington’s disease Metabolon will test plasma samples obtained from patients; they want to find markers to diffferentiate controls and disease (1/19) MicroIslet Inc. (AMEX:MII) Mayo Foundation for Medical Education and Research Supply agreement Mayo will supply Designated PathogenFree pigs to MicroIslet for use in development of MicroIslet-P The product entails use of porcine islets in diabetes; the agreement is exclusive in diabetes during the deal and could lead to a long-term supply agreement (3/15) Millenia Hope Inc. (OTC BB:MLHP) University of West Virginia License agreement Millenia acquired all rights to the Phase III product tetrandrine The drug is being developed for malaria and cancer applications; the deal was made with the inventor at the university (2/1 1) Nanobac Life Sciences Inc. (OTC BB:NNBP) University of South Florida Collaboration For research related to the prevalence and implications of nanobacteria in environmental samples The focus is on water distribution systems and possible treatment methods; terms were not disclosed (2/4) Narhex Life Sciences Ltd. (Australia; ASX:NLS) National Institute Collaboration of Allergy and Infectious Diseases They will evaluate the protease inhibitor Nar DG 35 Prodrug Narhex’s drug will be studied for actvity against hepatitis C and the SARS virus (1/1 1) NuGEN Technologies Inc.* AMDeC Foundation Agreement NuGEN will provide RNA amplification systems to AMDeC member institutions AMDeC promotes biomedical research in New York; terms of the deal were not disclosed (3/9) Osteotech Inc. (OSTE) Rutgers University License agreement Osteotech got rights to a polymer class for use as part of its Plexus technology Rutgers get $50,000 up front and up to $650,000 in milestone payments, as well as license fees and royalties on sales (2/3) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 317 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) OXIS International Inc. (OTC BB:OXIS) Various scientists and laboratories Collaboration To develop an oxidative stress paradigm to diagnose early onset of human and animal diseases OXIS intends to develop diagnostic biomarkers for a number of diseases, working with specialists in the disease areas (1/12) PamGene International BV* (the Netherlands) Netherlands Proteomics Centre Collaboration To further develop technology for proteomics research The work will focus on functional proteomics; details were not disclosed (3/8) ParAllele BioScience Inc.* University of Iowa Collaboration To accelerate the discovery of genes associated with agerelated macular degeneration Iowa researchers will use the pharmacogenomics and highthroughput gene mutation discovery technologies of ParAllele in their research (3/29) Perligen Sciences Inc.* University of Cambridge, Cancer Research Technology and Cancer Research UK (all in the UK) Collaboration To conduct a wholegenome association study on breast cancer Cancer Research UK is funding the work, which will determine more than 200 million individual genotypes in DNA samples collected from patients (2/16) Prolexys Pharmaceuticals Inc.* Massachusetts Institute of Technology License agreement Prolexys got rights to a series of small molecules with cancerspecific cytotoxic properties MIT acted as licensing agent for Whitehead Institute for Biomedical Research and Columbia University; terms were not disclosed (2/23) Resverlogix Corp. (Canada; TSE:RVX) Cedars-Sinai Medical Center Collaboration They will work on Resverlogix’s Nexvas compounds for treating cardiovascular diseases The work is being done with atherosclerosis researcher Prediman Shah; terms were not disclosed (1/26) Serologicals Corp. (SERO) University of California License agreement Serologicals subsidiary Upstate Group got rights to sell the anti-ZAP-70 monoclonal antibody for diagnostic uses Expression levels of the ZAP-70 protein have been shown to predict the aggressiveness of chronic lymphocytic leukemia; terms of the deal were not disclosed (3/28) Sigma-Aldrich Corp. (SIAL) Massachusetts Institute of Technology Agreement Sigma-Aldrich will serve as scientific collaborator and distribution partner of The RNAi Consortium The consortium based at The Broad Institute includes seven research institutions and four commercial partners; its goal over three years is to create a library of RNAi reagents (3/15) 318 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Somaxon Pharmaceuticals Inc.* University of Miami License agreement Soma xon got rights to a patent on the use of oral nalmefene hydrochloride for treating nicotine dependence The deal extends the scope of rights for Somaxon, which previously licensed rights from BioTie Therapies Corp. (2/22) SurModics Inc. (SRDX) Rutgers University License agreement SurModics got an option to acquire an exclusive license to two classes of biodegradable polymers The polymers will be used for site-specific delivery of drugs to the eye; terms of the deal were not disclosed (3/29) U.S. BioDefense Inc. (OTC BB:UBDE) University of Minnesota License agreement U.S. BioDefense got a six-month option to license a patent on hematopoietic stem cells The patent covers a method for selective engraftment of drugresistant stem cells, which can be applied to gene therapy; terms were not disclosed (3/21) U.S. BioDefense Inc. (OTC BB:UBDE) University College London License agreement U.S. Bio got a 90-day option to hepatic stem cell sorting and enrichment technology The technology will be evaluated for therapeutic repopulation of stem cells in liver disease (2/23) U.S. BioDefense Inc. (OTC BB:UBDE) Undisclosed university Option agreement U.S. Biodefense will evaluate an adult stem cell sorting and enrichment technology The option is expected to be exercised in June, when further details would be disclosed (1/25) Xenova Group plc (UK; XNVA) Cancer Research Technology Ltd. (UK) License agreement CRT got rights to TA-CIN, which is being developed for treating cervical dysplasia CRT intends to initiate further trials and to sublicense the vaccine; they would share revenues from licensing deals (1/10) Ziopharm Inc.* Southern Research Institute Collaboration Two-year deal to develop a series of isophosphoramide mustard analogues Ziopharm also got an option to exclusive worldwide rights on the alkylating agents (1/7) SECOND QUARTER Ablynx NV* (Belgium) National Research Council of Canada Collaboration The work focuses on Nanobodies developed at the NRC that cross the blood-brain barrier They plan to develop drugs and diagnostics for central nervous system diseases, initially Alzheimer’s disease; terms were not disclosed (5/26) Aegis Therapeutics Inc.* Albany Medical College License agreement Aegis got rights to the college’s anti-obesity peptide Aegis will assess the peptide with its Intravail intranasal delivery technology; terms of the deal were not disclosed (5/16) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 319 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) AEterna Zentaris Inc. (Canada; AEZS) Julius Maximilians University (Germany) Collaboration Deal to develop tumor vaccines based on attenuated bacterial carriers AEterna also acquired rights to immunotherapeutic approaches against cancer and bacterial tumor targeting; terms were not disclosed (4/21) Affitech A/S* (Norway) Research Foundation of the Norwegian Radium Hospital License agreement Affitech got exclusive rights to cancerspecific human antibodies Affitech and the hospital have been collaborating in the area, using Affitech’s Cell-Based Antibody Selection technology; terms were not disclosed (5/18) Akubio Ltd.* (UK) U.S. Army Collaboration To develop improved systems for detecting bioterrorism agents The work will be done with the U.S. Army Medical Research Institute of Infectious Diseases and is being supported by $3M from the National Institute of Allergy and Infectious Diseases (5/17) Alnylam Pharmaceuticals Inc. (ALNY) Max Planck Society (Germany) License amendment Amended deal reinforces Alnylam’s exclusivity for the “Tuschl II” patent application The patent is one believed by the company to be fundamental for RNA interference; Alnylam will issue 270,000 shares to Max Planck and other co-owners of the technology (6/16) Alnylam Pharmaceuticals Inc. (ALNY) University of Georgia Collaboration To discover and develop RNAi-based therapeutics for newly emerging strains of influenza virus Alnylam intends to discover siRNAs that target flu genes required for viral replication and have antiviral activity; terms of the deal were not disclosed (6/25) Andara Life Science Inc.* Purdue University License agreement Andara got rights to develop the oscillating field stimulator technology The technology is designed to stimulate nerve regeneration and has applicability in central nervous systems diseases; terms were not disclosed (4/14) Applied Imaging Corp. (AICX) University of Vermont Collaboration To further develop and validate technology to detect and characterize circulating tumor cells in the blood Applied Imaging subsidiary CTC Inc. will work with the university in the deal, terms of which were not disclosed (5/26) Arrowhead Research Corp. (ARWR) Stanford University License agreement Arrowhead licensed a nanotech device designed to control the behavior of adult stem cells Arrowhead will fund additional research on the device in exchange for the right to exclusively license the technology (6/6) 320 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Arrowhead Research Corp. (ARWR) Ludwig Maximilians University (Germany) Patent acquisitions The patents cover nanosensor technology for use in disease diagnosis The portfolio covers techniques for measuring biomolecular interactions by single-moleculeforce spectroscopy; it complements Arrowhead’s IP (5/19) Avantogen Ltd. (Australia; ASX:ACU) University of Alabama at Birmingham Collaboration For preclinical studies of a vaccine for herpes simplex virus type 2 UAB will use the firm’s GP1-0100 adjuvant with a live, attenuated HSV-2 vaccine candidate (6/7) BioCurex Inc.* (PK:BOCX) Center for Cancer Care Collaboration Deal to develop and evaluate BioCurex’s RECAF technology The technology is used in targeting cancer cells; terms of the deal were not disclosed (5/20) BioLineRx Ltd.* (Israel) Weizmann Institute of Science (Israel) License agreement BioLineRx licensed BL-2040, a small-molecule drug candidate The compound may have applications in treating hypertension, obesity and metabolic syndrome; terms were not disclosed (6/20) Bionaut Pharmaceuticals Inc.* National Cancer Institute Collaboration Deal to profile Bionaut cancer compounds that inhibit the ability of tumor cells to survive stress conditions They also will work to identify new biomarkers in tumor cells that are affected by Bionaut’s lead cancer compounds; terms were not disclosed (5/19) BioVeris Corp. (BIOV) University of Massachusetts at Amherst Option agreement BioVeris optioned rights to a vaccine candidate for Chlamydia Separately, BioVeris will sponsor up to $600,000 of research on the candidate at UMA through 2006; if optioned, UMA would get license fees and potential milestones and royalties (5/25) Biovitrum AB* (Sweden) Karolinska Institute (Sweden) Agreement Biovitrum will produce a protein for preclinical research based on a technique developed at the institute Biovitrum, on behalf of the Department of Woman and Child Health, will produce recombinant HMGB-1, which is implicated in inflammatory reactions (5/31) Bridge Pharmaceuticals* National Foundation for Cancer Research Collaboration They will jointly fund and manage cancer research programs in both the U.S. and Asia The goal is to accelerate discovery and development at a lower cost (5/17) CellCentric Ltd.* (UK) Babraham Institute (UK) License agreement CellCentric got rights to epigenetic-related intellectual property generated at Babraham CellCentric will use its discovery platform to develop cancer products and fund specific research at the institute (4/7) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 321 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Cenix BioScience GmbH* (Germany) Instituto de Medicina Molecular (Portugal) Collaboration They intend to identify human genes required for the malaria infection process The work, using an vitro assay system at the institute, is being funded by European agencies (6/29) ChemBridge Research Laboratories Inc.* St. Jude Children’s Research Hospital Inc. Collaboration They extended a previously unannounced deal on targets related to anaplastic lymphoma kinase They will apply CRL’s discovery medicinal chemistry platform to targets from St. Jude cancer research; terms of the deal were not disclosed (5/4) ChondroGene Ltd. (Canada; TSE:CDG) Lam Wa EE Hospital and Island Hospital (both in Malaysia) Collaborations The hospitals will provide clinical samples in a variety of disease areas The hospitals eventually will offer their patients molecular diagnostic tests and services from ChondroGene (6/10) Ciphergen Biosystems Inc. (CIPH) National Cancer Institute Material transfer agreement The NCI will evaluate Ciphergen Diagnostics’ ProteinChip technology and associated bioinformatics suites The NCI’s Clinical Proteomics Reference Laboratory will use the technology to study biomarker patterns indicative of ovarian cancer (4/28) CODA Genomics Inc.* University of California at Irvine License agreement CODA got rights to Computer Optimized DNA Assembly (CODA) and protein-expression optimization technology The company was formed to commercialize the technology; terms of the deal were not disclosed (4/27) Cryptome Pharmaceuticals Ltd. (Australia; ASX:CRP) Murdoch License Childrens agreement Research Institute (Australia) Cryptome got rights to two unique proteins to mine for novel drug candidates Cryptome gets all rights to products emerging from the deal, terms of which were not disclosed (4/8) Cryptome Pharmaceuticals Ltd. (Australia; ASX:CRP) Northeastern University Agreement Cryptome got rights to use the university’s technology to identify and isolate low-abundance human proteins Cryptome gets rights to drug candidates emerging from the deal, terms of which were not disclosed (4/6) Cytheris* (France) New York University, the City University of New York and the Aaron Diamond AIDs Research Center License agreement Cytheris got rights to a family of immunomodulating agents that activate NKT and dendritic cells Terms of the exclusive, worldwide deal were not disclosed (5/23) CytoGenix Inc. (OTC BB:CYGX) University of Pennsylvania Agreement The university will perform animal studies for the company The tests will use the company’s synDNA technology to test a DNA vaccine against smallpox (6/21) 322 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit CytoGenix Inc. (OTC BB:CYGX) Type Of Agreement Product Area Details (Date) National Institutes Evaluation of Health license CytoGenix will conduct experiments using an HIV DNA vaccine The synthetic vaccine is derived from HIV gene sequences contained in an NIH plasmid; terms were not disclosed (5/25) Dharmacon Inc.* Cancer Research UK Agreement Dharmacon will provide siRNA libraries to Cancer Research UK The libraries initially include protein kinase genes and associated pathways; terms were not disclosed (4/18) Diversa Corp. (DVSA) Clemson University Collaboration To assess opportunities for Diversa enzymes in enhancing human nutrition The intitial focus is on evaluating the ability of protein supplements to improve stamina and alertness and reduce fatigue (6/2) DNAPrint genomics Inc. (OTC BB:DNAP) Beth Israel Deaconess Medical Center License agreement DNAPrint got rights to develop a new form of the anemia drug erythropoietin Terms of the worldwide, royaltybearing license were not disclosed (4/5) Duska Therapeutics Inc. (OTC BB:DSKT) Undisclosed European scientists License agreement Duska got exclusive rights to P2 receptorbased technology The technology is expected to have applicability in treating glaucoma; terms of the deal were not disclosed (6/15) Duska Therapeutics Inc. (OTC BB:DSKT) University of Pennsylvania Agreement Preclinical studies with ATPotent will be carried out at the university ATPotent, a liquid formulation of adenosine 5’-triphosphate, is being developed by Duska for treating male infertility (6/13) Elixir Pharmaceuticals Inc.* University of California License agreement Elixir got exclusive rights to technology covering SirT1 and the HIV TAT protein SirT1 is a member of the sirtuin class of enzymes; Elixir already had rights from UC to SirT2 and SirT3; they may have applicability in metabolic diseases, HIV and cancer (5/19) Enzo Biochem Inc. (NYSE:ENZ) Ludwig Maximilians University (Germany) Acquisition Enzo acquired rights to a candidate drug and technology for use in the treatment of uveitis The drug, which has orphan status in Europe, has been in a small Phase I trial in Germany; terms of the deal were not disclosed (6/9) Galapagos Genomics BV* (Belgium) Cystic Fibrosis Foundation Therapeutics Inc. Collaboration Galapagos will apply its technologies to discover and validate novel drug targets for CF Galapagos will get €1.3M from CFFT and has an option to further develop targets identified in the program (4/14) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 323 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Genedata AG* (Switzerland) NIH Chemical Genomics Center Collaboration Deal to integrate Genedata Screener software with the NCGC’s IT infrastructure The center will use the software system in its high-throughput screening efforts; terms of the deal were not disclosed (5/12) GeneGo Inc.* Translational License Genomics agreement Research Institute TGen licensed GeneGo’s MetaCore platform The platform is used for mining high-throughput experimental data; terms of the deal were not disclosed (5/16) GeneGo Inc.* National Cancer Institute License agreement The NCI licensed GeneGo’s MetaCore 2.5 platform The platform is used to mine high-throughput experimental data; terms were not disclosed (5/31) Generex Biotechnology Corp. (GNBT) The Scripps Agreement Research Institute Scripps researchers will test the potency of a modified DNA vaccine for treating various forms of cancer The deal was made between Scripps and Generex subsidiary Antigen Express; terms were not disclosed (5/1 1) GenoLogics Life Sciences Software Inc.* The Institute for Systems Biology Collaboration To increase the utility of ISB’s open-source software tools in the life sciences community GenoLogics will work to enhance the functionality and usability of the tools and integrate them into its ProteusLIMS platform (5/19) GenVault Corp.* University of Texas Agreement GenVault acquired full rights to DNA-labeling technology developed at the university The patent allows GenVault to offer and license its GenCode to a broader market; terms of the deal were not disclosed (5/1 1) Genzyme Corp. (GENZ) Massachusetts General Hospital and Dana-Farber Cancer Institute License agreement Genzyme got diagnostic rights to gene mutations recently found in some patients with nonsmall-cell lung cancer Genzyme intends to develop and market a test for EGFR markers that can be used to help identify patients most likely to respond to targeted therapies (5/2) Guava Technologies Inc.* AIDS Healthcare Foundation Partnership They intend to increase access in resourcelimited nations to AIDS diagnosis and treatment monitoring They will make Guava’s EasyCD4 system for counting CD4 T cells available at five sites; the program would be expanded after establishing feasibility (4/27) Helix BioPharma Corp. (Canada; TSE:HXB) National Research Council of Canada License agreement Helix licensed an antibody that targets cancerous tissue in the lung The antibody is being combined with Helix’s DOS47 drug candidate; Helix will make up-front and milestone payments (5/2) 324 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Immunetrics Inc.* Type Of Agreement Product Area Details (Date) University of Collaboration Cologne (Germany) and the Ludwig Boltzmann Institute (Austria) To discover biomarkers of inflammation for use in drug discovery and disease diagnosis and management The academic partners get access to Immunetrics’ modeling platform; the universities are providing a database of human and animal data (6/6) Ingenuity Systems Inc.* National Cancer Institute Center for Cancer Research License agreement The NCI licensed access to the Ingenuity Pathways Analysis software The technology includes millions of individually modeled relationships between proteins, genes, complexes, cells, tissues, drugs and diseases (4/12) InNexus Biotechnology Inc. (Canada; CDNX:IXS) Mayo Clinic Collaboration Deal focused on creation of new antibody-based therapies They intend to develop products for cancer, cardiovascular disease and other conditions under the multiyear agreement (5/17) Insilico GmbH* (Austria) German Resource Collaborattion Center for Genome Research To integrate various information for the use of research scientists The effort links the company’s MASI database with the center’s material index (6/1) IntegraGen SA* (France) Fondation Autisme (France) Agreement IntegraGen will use DNA samples collected by the foundation to validate its genetic test for autism IntegraGen is supporting the foundation with a donation and by helping to create a databank and repository of DNA samples (5/23) Intercell AG (Austria; VSE:ICLL) and Statens Serum Institut (Denmark) Aeras Global TB Vaccine Foundation Agreement Aeras will fund development of a prophylactic tuberculosis vaccine In return, Aeras will get a sublicense to the vaccine for a number of developing countries; SSI and Intercell retain rights elsewhere (6/27) Kalypsys Inc.* The Scripps Research Institute Agreement Scripps will access Kalypsys’ ultra-highthroughput screening technologies The technology will be used in Scripps’ newly created site in Florida; terms were not disclosed (6/15) Kane Biotech Inc. (Canada; TSE:KNE) University of Medicine and Dentistry of New Jersey License agreement Kane got rights to all human and industrial applications of the dispersin B enzyme Dispersin B is an enzyme responsible for the dispersal of bacterial biofilms; terms of the deal were not disclosed (4/26) Macrogenics Inc.* Washington University School of Medicine License agreement Macrogenics got rights to a monoclonal antibody against the West Nile virus Macrogenics participated in promising preclinical studies; terms of the license were not disclosed (4/22) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 325 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Nastech Pharmaceutical Co. Inc. (NSTK) Mayo Clinic Collaboration Mayo will evaluate Nastech’s RNAi-based formulations in immune cells from patients with rheumatoid arthritis The collaboration will involve the measurement of a series of inflammatory cytokines for the purpose of selecting a candidate for preclinical development (4/5) Neoprobe Corp. (OTC BB: NEOP) University of California at San Diego Option agreement Neoprobe got an option to expand the field of use for Lymphoseek The license was expanded to allow for use of the compound as an optical or ultrasound agent; terms were not disclosed (4/20) NephroGenex Inc.* Karolinska Institute (Sweden) License agreement NephroGenex acquired rights in the renal disease field to Goodpasture antigenbinding protein kinase technology GPBP kinase is active against extracellular matrix molecules; terms of the deal were not disclosed (5/5) NephroGenex Inc.* Biomedical Research Foundation (Spain) License agreement NephroGenex acquired rights to glomerular transcriptome profiling technology The molecular profiling technology is used to identify renalspecific pathogenic pathways (5/5) Neurologix Inc. (OTC BB:NRGX) Keio University (Japan) License agreement Neurologix got rights outside Japan to the humanin gene The gene, which may prevent amyloid toxicity, will be used as an approach to treating Alzheimer’s and other CNS diseases (5/18) Nonlinear Dynamics Ltd.* (UK) Australian Proteome Analysis Facility Ltd. License agreement The APAF purchased two licenses to the company’s Progenesis Discovery v2005 The product is a 2-D gel image analysis platform; terms of the licenses were not disclosed (6/16) OncoGenex Technologies Inc.* University of British Columbia (Canada) License agreement OncoGenex got rights to inhibitors of heatshock protein 27 The lead product, OGX-427, is expected to enter clinical development in 2006; terms were not disclosed (4/26) OncoMethylome Sciences SA* (Belgium) Max Planck Society (Germany) License agreement OncoMethylome got rights to technology for silencing tumorsuppressor genes by DNA methylation The technology will be used for early prostate cancer detection, prognosis and monitoring of recurrence; terms were not disclosed (5/17) Orion Genomics LLC* Johns Hopkins University School of Medicine Collaboration To better understand the role of DNA’s “Second Code” in colon cancer They will study DNA methylation with the goal of developing a diagnostic test for the cancer’s early detection (6/7) 326 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Ortec International Inc. (OTC BB:ORTN) University of California at Berkeley Collaboration To evaluate Ortec’s collagen scaffold for use in cardiovascular tissue regeneration The work is being done with the university’s Center for Tissue Engineering; terms were not disclosed (5/19) ParAllele BioScience Inc.* Baylor University Collaboration To measure the genetic basis of patient response to the flu vaccine They will use ParAllele’s SNP genotyping panel in the effort; terms were not disclosed (4/27) ParAllele BioScience Inc.* University of Southern California Collaboration To discover genes associated with lupus They will use ParAllele’s SNP genotyping panel in the effort; terms were not disclosed (4/27) Peregrine Pharmaceuticals Inc. (PPHM) National Institute Collaboration of Allergy and Infectious Diseases The NIAID will screen Anti-Phospholipid Therapy agents, including Tarvacin Peregrine’s compounds will be screened for activity against various enveloped viral pathogens of health and bioterrorism concern (4/4) Perlegen Sciences Inc.* Women’s Health Initiative Deal to conduct a high-density wholegenome scan of single nucleotide polymorphisms The SNPs will be in relation to coronary heart disease, stroke and breast cancer, and combined postmenopausal hormone therapy; work is being funded by the National Heart, Lung and Blood Institute (6/30) Pharmacopeia Drug Discovery Inc. (PCOP) Columbia Amended University and license Cold Spring agreement Harbor Laboratory The deal covers the company’s ECLiPS tagging technology Pharmacopeia said it also resolved a prior dispute regarding payment of royalties under the initial deal; terms were not disclosed (5/26) PharmaStem Therapeutics Inc.* University of Texas M.D. Anderson Cancer Center License agreement The cancer center licensed PharmaStem’s technology for the storage and use of umbilical cord blood The technology is covered under five patents; PharmaStem is entitled to certain milestone payments (4/20) PPD Inc. (PPDI) Duke University License agreement Duke got rights to develop a portfolio of geranylgeranyl transferase inhibitors Duke will fund R&D, and would share equally with PPD any future payments by third parties (6/22) ProChon Biotech Ltd.* (Israel) Musculoskeletal Transplant Foundation Collaboration To develop products combining ProChon’s growth factor and cell technology with MTF’s allograft and tissue materials The two deals include an equity investment agreement; MTF will provide R&D funding and be responsible for development and commercialization (4/10) Collaboration BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 327 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Proteome Systems Ltd. (Australia; ASX:PXL) Foundation for Innovative New Diagnostics (Switzerland) Collaboration Letter of intent to fast-track development of an antigen-based diagnostic for detecting active tuberculosis Proteome Systems’ test would detect TB antigens and monitor disease progression and treatment response; details were not disclosed (6/21) pSivida Ltd. (Australia; PSDV) University of South Australia Collaboration Deal to evaluate pSivida’s BioSilicon platform for drug delivery The university’s Ian Wark Research Institute will evaluate the controlled-release technology under a six-month deal (6/20) Reata Pharmaceuticals Inc.* University of License Texas Southagreement western Medical Center and Victoria University (New Zealand) Reata got exclusive worldwide rights to a new class of anticancer compounds The lead compound, peloruside A, was discovered in a marine sponge in New Zealand’s Pelorus Sound; terms of the deal were not disclosed (5/10) Sareum Holdings plc (UK; AIM:SAR) Cancer Research Technology Ltd. (UK) Collaboration extension Sareum will provide computational chemistry services for a further six months The initial fee-for-service deal related to cancer discovery programs at CRT was signed in December 2004; terms were not disclosed (4/1 1) Senesco Technologies Inc. (AMEX:SNT) University of Pittsburgh Funded research The company will fund work on inflammatory bowel disease models The study will assess inhibition of the company’s Factor 5A gene technology on IBD (5/12) Senesco Technologies Inc. (AMEX:SNT) University of Virginia Funded research The company will fund an in vitro bladder cancer study The study will assess up-regulation of the company’s Factor 5A gene on bladder cells (5/12) Senetek plc (OTC BB:SNTKY) Unnamed research foundation License extension Senetek got rights to diagnostic monoclonal antibodies used for research in various disease states The deal was extended through 201 1; Senetek would pay royalties on any resulting sales (4/7) Sirna Therapeutics Inc. (RNAI) Massachusetts General Hospital Sponsored research For research into using siRNAs and related formulations as modulators of the retinoblastoma gene pathway The goal is to promote regrowth and differentiation of hair cells that under natural conditions do not grow or divide in adult mammals (6/13) Sirtris Pharmaceuticals Inc.* Washington University School of Medicine License agreement Sirtris got exclusive rights to technology related to Class III histone deacetylases The technology, also known as sirtuins, may have applicability in neuroprotection; terms were not disclosed (5/19) 328 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Stratagene Corp. (STGN) Sidney Kimmel Cancer Center License agreement Stratagene got rights to technology on a novel methodology for discovering cancerrelated genes Stratagene also got exclusive rights to certain gene groups that may have predictive capabilities in cancer; terms of the deal were not disclosed (4/15) Telik Inc. (TELK) Mount Sinai School of Medicine Collaboration Deal to discover and evaluate small molecules for new cancer targets They will use Telik’s TRAP discovery technology in the effort; terms of the deal were not disclosed (4/22) Tm Bioscience Corp. (Canada; TSE:TMC) Akron Children’s Hospital Supply agreement Tm will provide Tag-It reagents to the hospital The hospital will use the reagents in its cystic fibrosis gene assay; terms were not disclosed (5/18) Tm Bioscience Corp. (Canada; TSE:TMC) McMaster University (Canada) Collaboration To develop an upper respiratory viral panel They will use Tag-It technology from Tm, which would commercialize resulting products (5/9) TopoTarget A/S* (Denmark) and CuraGen Corp. (CRGN) National Cancer Institute Cooperative Research and License Agreement Deal to conduct preclinical studies on PXD101 to better understand its antitumor activity An additional goal will be to select the best next generation of histone deacetylase inhibitors for development (5/12) U.S. BioDefense Inc. (OTC BB:UBDE) University of Texas M.D. Anderson Cancer Center License agreement U.S. BioDefense got an option to review and license technology from the cancer center The technology covers the use of non-marrow stem cells for cardiac regeneration; terms of the deal were not disclosed (5/10) Valentis Inc. (VLTS) Vanderbilt University License agreement Valentis gained rights to the Del-1 antibody and associated intellectual property Valentis had licensed rights to the Del-1 protein and gene in 1998; Del-1 is an angiogenic protein; terms were not disclosed (5/19) Viragen Inc. (AMEX:VRA) University of Miami Option termination Viragen chose not to license VG104, the IEP 1 1 peptide with applicability in cancer The option expired and all development activities relating to VG104 have been discontinued (5/18) Viragen Inc. (AMEX:VRA) Cancer Research Technology Ltd. (UK) License agreement Viragen got exclusive rights to commercialize an anti-CD55 antibody The antibody (VG102) is in preclinical development for treating a range of cancers; terms of the deal were not disclosed (5/9) Xenomics Inc. (OTC BB:XNOM) Eastern Virginia Medical School Research agreement Deal to study Xenomics’ technology for detecting Down synsyndrome in unborn children The technology entails analysis of maternal urine samples; terms were not disclosed (5/12) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 329 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Xenomics Inc. (OTC BB:XNOM) North ShoreLong Island Jewish Health System Research agreement Deal to study the use of DNA technology to detect a number of fetal genetic problems They intend to conduct clinical trials of the company’s Transrenal DNA product; terms were not disclosed (5/12) Xsira Pharmaceuticals Inc.* Harbor-UCLA Medical Center License agreement Xsira got rights to develop adenosine as an analgesic for postoperative pain Initial studies of adenosine in the surgical setting already have been conducted; terms of the worldwide license were not disclosed (4/14) Acambis plc (UK; ACAM) Flanders Interuniversity Institute for Biotechnology (Belgium) Collaboration To develop a vaccine against both the A and B strains of influenza The goal is to generate a candidate that would protect against both strains and would not require annual formulation changes (8/4) Advanced Cell Technology Inc. (OTC BB:ACTC) The Burnham Institute Collaboration For research that aims to isolate stem cellspecific differentiation markers They will use particle display technology to identify markers for many of the lineages of cells that make up the human body (7/27) Amplimed Corp.* University of Arizona License agreement Amplimed got rights to a porfolio of compounds, including the cancer agent FB642 A university-related company gets equity in Amplimed, along with potential milestone and royalty payments (8/9) Affymetrix Inc. (AFFX) Broad Institute of MIT and Harvard Agreement The institute will use the GeneChip Mapping 500K Set for genomewide association studies The institute gained use under Affymetrix’s early access program; the institute and collaborators intend to generate genotypes relevant to multiple diseases (7/21) Albany Molecular Research Inc. (AMRI) National Institute of Neurological Disorders and Stroke Collaboration Two-year deal aimed at developing treatments for spinal muscular atrophy AMRI will provide medicinal chemistry services on a fee-forservices basis (7/1 1) Alnylam Pharmaceuticals Inc. (ALNY) and Isis Pharmaceuticals Inc. (ISIS) Stanford University License agreement The companies got co-exclusive rights to technologies in the area of hepatitis C virus The technology relates to the inhibition of the liver-specific microRNA miR-122; terms were not disclosed (9/13) THIRD QUARTER 330 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Altachem Pharma Ltd. (Canada; CDNX:AAF) Research Centre for Bioactive Materials (Korea) Agreement They will work together to plan the most appropriate projects for Altachem The goal is to establish projects designed to underpin Altachem’s discovery programs in cancer (9/8) Amaxa GmbH* (Germany) American Type Agreement Culture Collection ATCC will supply cell lines to Amaxa The cell lines will be used to develop and optimize protocols using Amaxa’s Nucleofector technology (9/27) Ambion Inc.* MitoChek consortium Agreement Ambion will provide the consortium a genome-wide siRNA library targeting every human gene The European Union-funded consortium will use the library to research how cell division is regulated; terms of the deal were not disclosed (8/12) Applied Biosystems Group (NYSE:ABI) National Institute of Genomic Medicine of Mexico Collaboration To establish an Applied Biosystems sequencing and genotyping unit at the institute They also will conduct research studies focused on health issues important to the Mexican population (7/25) Artemis Pharmaceuticals GmbH* (Germany) Max Delbruk Collaboration Center for Molecular Medicine and the University of Wurzbur (both in Germany) Three-year deal to develop and validate methods for the functional analysis of disease-related genes in transgenic rats The work will be jointly funded by Artemis and the RiNA RNANetwork; Artemis gets rights to resulting products through a license agreement with RiNA GmbH, an entity of the German government (7/19) Ascentia Biomedical Corp. (OTC BB:ASCE) University of Washington Option agreement Ascentia got rights to a family of compounds potentially applicable to a number of diseases Terms of the option were not disclosed; the compounds are being developed for cancer, sepsis, autoimmune diseases and for use in vaccines (8/15) Biolog Inc.* and Axiohelix* (Japan) NARA Institute (Japan) Collaboration They extended deal to phenotype and determine the function of each gene in the E. coli genome Work on the project began in November 2004; terms of the deal were not disclosed (7/26) BioSante Pharmaceuticals Inc. (AMEX:BPA) Wake Forest University and Cedars Sinai Medical Center License agreement BioSante exercised its option to license triplehormone contraception technology The technology covers combinations of estrogens and progestins with androgens; BioSante will make up-front and maintenanace payments, along with potential milestones and royalties (8/10) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 331 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Biosite Inc. (BSTE) Johannes Gutenberg University (Germany) License agreement Biosite got exclusive rights to caspase-1, a potential biomarker for cardiovascular disease Biosite is collaborating with the University of Mainz to investigate clinical applications; terms of the deal were not disclosed (8/22) Biosite Inc. (BSTE) Cincinnati Children’s Hospital Medical Center and Columbia University License agreement Biosite got rights to neutrophil gelatinaseassociated lipocalin, a potential biomarker for identifying acute renal failure Biosite will make antibodies to NGAL; the NGAL immunoassay then will be tested on blood samples to assess its potential; terms of the exclusive license agreement were not disclosed (7/13) BioVeris Corp. (BIOV) The Rockefeller University License agreement BioVeris got exclusive rights to technologies related to a Group A Streptococcal disease vaccine candidate BioVeris paid a $150,000 license fee and may make additional payments for license maintenance and patent costs, as well as making milestone and royalty payments (9/6) Cambria Biosciences LLC* Northwestern University Collaboration To screen existing compounds for activity against amyotrophic lateral sclerosis The work is being funded by a grant from the ALS Association (8/8) Catalyst Biosciences Inc.* Torrey Pines Institute for Molecular Studies License agreement Catalyst got rights to use technology for protease engineering, selection and optimization The license covers a protease selection technology and solidifies and expands Catalyst’s position in proteases (7/25) CellCentric Ltd.* (UK) Cancer Research Technology Ltd. (UK) Collaboration To develop monoclonal antibodies against CellCentric’s epigeneticrelated cancer target They will share the costs and rewards of the effort, which may be followed by co-development of other targets identified by CellCentric (9/26) ChemDiv Inc.* Scripps Florida Collaboration They extended deal giving Scripps access to ChemDiv screening libraries Terms of the deal were not disclosed (7/21) Chlorogen Inc.* Rutgers University License agreement Chlorogen got exclusive The deal also gives Chlorogen rights to chloroplast limited rights to certain future transformation patents discoveries by Rutgers from research in the field (8/16) 332 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) ChondroGene Ltd. (Canada; TSE:CDG) University of California at San Francisco Alliance Deal setting framework for collaborations applying the Sentinel Principle to new drugs and diagnostics The Sentinel Principle is the company’s approach to detect and stage diseases or conditions from a blood sample; ChondroGene would have rights or options to resulting products (8/10) Ciphergen Biosystems Inc. (CIPH) University of Kentucky Collaboration Ciphergen got exclusive rights to license discoveries; the focus is on ovarian cancer Ciphergen will provide its suite of proteomic solutions for biomarker discovery and development of assays to the effort; terms were not disclosed (8/24) CombiMatrix Group (CBMX) Biodesign Institute at Arizona State University Collaboration To develop a peptide array synthesizer using CombiMatrix’s virtualflask technology The institute is purchasing CombiMatrix equipment and funding development; any revenues would be shared (8/12) Corautus Genetics Inc. (VEGF) Caritas St. Elizabeth’s Medical Center Agreement Corautus will provide its VEGF-2 product for evaluation in a Phase I trial in diabetic neuropathy Corautus would get rights in that indication; also, Corautus licensed certain technology, including the use of angiogenic growth factors in peripheral neuropathy; the center is entitled to up-front, milestone and royalty payments (8/10) Crucell NV (the Netherlands; CRXL) Naval Medical Research Center of the U.S. Navy Cooperative Research and Development Agreement To construct AdVacbased vaccines against anthrax and plague and test them in nonhuman primates Crucell got an option for exclusive rights to any vaccine that may result from the deal (8/17) Cryptome Pharmaceuticals Ltd. (Australia; ASX:CRP) University of Virginia Collaboration expansion To further discover compounds that treat vascular leak Cryptome gets the first option to license CR104 and other technology developed at the university (9/19) Cyberkinetics Neurotechnology Systems Inc. (OTC BB:CYKN) Brown University Collaboration Brown researchers get access to clinical research data provided by Cyberkinetics The company gets options to license inventions derived from the research, which is in the area of neurology (9/8) CytoGenix Inc. (OTC BB:CYGX) Imperial College London Collaboration For research studies using the company’s antimicrobial nucleic acid compound College researchers will further elucidate the antimicrobial activity of CytoGenix’s RBL-1 compound (8/9) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 333 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Digene Corp. (DIGE) Georgetown University Settlement and license agreement They settled litigation relating to patents covering human papillomavirus Georgetown will get payments totaling $7.5M, and royalties on sales of 5% to 6% (7/14) DOR BioPharma Inc. (AMEX:DOR) and Cambrex Corp. SRI International Collaboration SRI is assisting in the development of the recombinant ricin vaccine RiVax SRI will optimize the immune response to the vaccine and perform preclinical safety testing; terms were not disclosed (7/5) EntreMed Inc. (ENMD) National Cancer Institute Cooperative Research and Development Agreement To evaluate the role of HIF-1-alpha inhibition in the treatment of cancer The three-year deal centers on EntreMed’s 2ME2 and analogues; terms of the deal were not disclosed (9/15) Galapagos NV (Belgium; Euronext: GLPG) High Q Foundation Inc. Collaboration Two-year deal to discover targets and develop drugs for Huntington’s disease Galapagos may receive up to $3M in the deal and has the option to further develop certain targets identified (8/12) Galapagos NV (Belgium; Euronext: GLPG) Leiden University (the Netherlands) Collaboration To pursue a smallmolecule drug discovery program in arthritis The four-way collaboration also includes ZoBio BV and Pyxis Discovery BV (8/10) GenoMed Inc. (PK:GMED) International Disease Management Alliance Agreement GenoMed joined the alliance, which was formed to promote disease management Details on GenoMed’s role in the alliance were not disclosed (7/13) Genospectra Inc.* CRNS (France) Agreement To develop a panel of optimized delivery reagents Genospectra also gets an exclusive license to “MPG” technology developed at the CNRS, and to products resulting from the collaboration (7/19) Gilead Sciences Inc. (GILD) and Royalty Pharma Emory University Agreement Gilead and Royalty purchased Emory’s royalty interest in the HIV drug emtricitabine (Emtriva) Emory got a one-time cash payment of $525M, with 65% of it coming from Gilead; Gilead is obligated to pay royalties on future sales to Royalty Pharma (7/18) Illumina Inc. (ILMN) Wellcome Trust (UK) Collaboration To study the impact of those SNPs that cause amino acid changes, on a range of disease samples They will design a custom Sentrix BeadChip for the effort; Illumina intends to turn the custom SNP product into a standard microarray offering (9/28) Illumina Inc. (ILMN) Max Planck Institute of Psychiatry (Germany) Supply agreement Illumnia will supply technologies for a large-scale genotyping study The institute intends to generate information on genetic variants associated with depression and anxiety (9/20) 334 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Illumina Inc. (ILMN) National Cancer Institute Purchase agreement The NCI is purchasing an Illumina BeadLab, a production-scale genetic analysis laboratory The lab will be used in research into the genetics of breast and prostate cancers, supporting the Cancer Genetic Markers of Susceptibility initiative (9/1) InforSense Ltd.* (UK) National Cancer Institute Agreement The NCI will use the company’s technology for high-throughput genetic data analysis The NCI will use the KDE InforSense integrative analytics platform under a five-year deal; terms were not disclosed (8/30) Invitrogen Corp. (IVGN) Fred Hutchinson Cancer Research Center Collaboration To develop diagnostics and screening tools for cancer Invitrogen has rights to license resulting technologies; terms were not disclosed (9/13) Invitrogen Corp. (IVGN) The Scripps Research Institute Collaboration To develop improved Invitrogen will have the right to methods for expression, commercialize resulting technolisolation and character- ogies (8/25) ization of membrane proteins JPT Peptide Technologies GmbH* (Germany) Oregon Health & Science University Collaboration Deal to discover T-cell epitopes to accelerate the development of tuberculosis vaccines JPT, a subsidiary of Jerini AG, will apply its high-throughput peptide synthesis and screening platform in the effort (7/7) Knopp NeuroSciences Inc.* University of Pittsburgh License agreement Knopp got rights to commercialize a panel of protein biomarkers The biomarkers will be used as a diagnostic test for amyotrophic lateral sclerosis (9/7) Agreement The ISB will use the Universal Linkage System from Kreatech The agreement is expected to help Kreatech position the labeling technology in new application areas (9/21) Kreatech Institute of Biotechnology Systems Biology BV* (the Netherlands) Lipid Sciences Inc. (LIPD) Washington Collaboration Hospital Center and MedStar Research Institute To broaden the scope of the company’s HDL therapy platform The deal allows Lipid to expand the program into the area of HDL mimetic peptides; terms were not disclosed (8/25) Lorus Therapeutics Inc. (Canada; AMEX:LRP) Ohio State University Collaboration Deal to study Lorus’ GTI-2040 and cytarabine on acute myeloid leukemia cell lines Lorus will work with the OSU Comprehensive Cancer Center in the research collaboration (9/7) Maas BiolAB LLC* Walter Reed Army Institute of Research Cooperative Research and Development Agreement Deal to develop cyclosporin neuroprotection in indications relevant to military casualties and homeland security They will further collaborate to develop Maas’ cyclosporin formula NeuroSTAT in models of traumatic brain injury and nerve gas poisoning (7/12) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 335 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Macrogen Inc.* (South Korea) National Institute of Toxicological Research (South Korea) Agreement Macrogen will provide gene expression analysis services to the NITR The services will use the Applied Biosystems Group Expression Array System; terms were not disclosed (8/9) MedImmune Inc. (MEDI) National Institute Collaboration of Allergy and Infectious Diseases To produce and test versions of MedImmune’s influenza vaccine against potential pandemic strains MedImmune also has offered licenses for its reverse genetics technology to U.S. and international authorities and manufacturers developing pandemic influenza vaccines (9/28) MedImmune Inc. (MEDI) Georgetown University Collaboration To develop monoclonal antibodies targeting anaplastic lymphoma kinase, a member of the insulin receptor family Georgetown gets an up-front payment and potential milestones and royalties; MedImmune gets exclusive worldwide rights to the preclinical program (9/26) Medivation Inc. (OTC BB:MDVN) University of California at Los Angeles Acquisition Medivation acquired the MDVN 300 series of small-molecule compounds The compounds target hormonerefractory prostate cancer; terms of the deal were not disclosed (9/19) Meridian Bioscience Inc. (VIVO) National Institutes of Health License agreement Meridian got rights to recombinant parvovirus B19 vaccine technology The license went to Meridian subsidiary Viral Antigens Inc.; Meridian previously had a contract to manufacture the vaccine (7/7) MerLion Cancer Research Pharmaceuticals Technology Ltd. Pte. Ltd.* (Singapore) (UK) Collaboration Screening program to identify anticancer drugs derived from natural product chemistry Resulting technology will be jointly owned (9/20) MerLion Institute of Pharmaceuticals Molecular and Pte. Ltd.* (Singapore) Cell Biology (Singapore) Collaboration Three-year deal to discover and develop cancer drugs; the initial focus is the Bcl-2 family of proteins IMCB will provide certain drug targets and projects; MerLion will provide natural product sample collections, and apply screening and chemistry skills; they will share resulting ownership (7/1) Mesoblast Ltd. (Australia; ASX:MSB) Colorado State University Agreement CSU will perform preclinical studies of Mesoblast technology CSU will test universal stem cell technolgoy for bone regeneration under undisclosed terms (7/21) MicroIslet Inc. (AMEX:MII) The Scripps Research Institute Collaboration They extended for two years work to develop islet cell transplantation therapies The focus is on diabetes; MicroIslet is providing financial support and technical assistance and has the option to retain all commercial rights (8/31) 336 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Millenium Biologix Corp. (Canada; TSE:MBC) Massachusetts Institute of Technology License agreement Millenium got rights to technology for certain uses of growth factors Millenium plans to develop a specific combination of growth factors in its Autologous Clinical Tissue Engineering Systems for cartilage repair (8/30) NeoRx Corp. (NERX) Scripps Florida Collaboration To discover smallThe goal is to identify potential molecule protein kinase cancer treatments (8/4) inhibitors as therapeutic agents Neuren Pharmaceuticals Ltd. (Australia; ASX:NEU) Walter Reed Army Institute of Research Expanded agreement The deal is for development of Neuren’s NNZ-2566 for traumatic brain injury They will explore the use of Walter Reed’s model for predicting clinical outcomes; Walter Reed will fund half of preclinical research; Neuren retains all rights outside the U.S. military (7/8) New River Pharmaceuticals Inc. (NRPH) University of California at San Francisco License agreement New River got rights to an approach to improve the use of opioid analgesics by reducing tolerance development UCSF’s Ernest Gallo Clinic and Research Center is entitled to a license fee and potential milestone and royalty payments (7/8) Novelos Therapeutics Inc. (OTC BB:NVLT) Medical University of South Carolina Collaboration To research the mechanisms of Novelos’ NOV-002 and NOV-205 products Results will help in the design and execution of clinical trials in cancer and hepatitis C, respectively (9/13) Odyssey Thera Inc.* National Institutes Agreement of Health Odyssey gave the NIH access to human cell lines with PCA technology for screening biochemical pathways Odyssey is providing access to the NIH Chemical Genomics Center as part of the NIH’s Molecular Libraries Roadmap Initiative (8/17) OriGene Technologies Inc.* Massachusetts General Hospital Collaboration Deal to use OriGene’s FlagArray platform for high-throughput functional analysis of genes Terms of the deal were not disclosed (7/25) Orion Genomics LLC* Washington University Collaborations To discover biomarkers for use in development of tests for cancer They will look for “Second Code” biomarkers for tests to screen for cancer at an early stage and to help guide treatment (8/9) Peregrine Pharmaceuticals Inc. (PPHM) U.S. Army Medical Research Institute of Infectious Diseases Cooperative Research and Development Agreement USAMRIID will study the potential of Tarvacin in treating hemorrhagic diseases Peregrine will supply the antiphospholipid therapy; it will be studied for hemorrhagic diseases resulting from Ebola and Marburg viral infections (7/21) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 337 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Perlegen Sciences Inc.* RIKEN (Japan) Collaboration They will use Affymetrix Inc. technology to conduct whole-genome association studies in Japan The goal is to identify the genetic causes of up to 47 common diseases; Perlegen’s subsidiary in Japan will work with RIKEN (7/20) Perlegen Sciences Inc.* Pritzker NeuroCollaboration psychiatric Disorders Research Consortium Perlegen is conducting a high-density wholegenome association study of bipolar disorder Results of the work are expected to help diagnose and treat neuropsychiatric diseases; terms of the deal were not disclosed (7/14) Phogen Ltd. (UK; joint venture of Xenova Ltd.) Cancer Research Technology Ltd. (UK) Agreement CRT will help commercialize Phogen’s VP22 technology CRT will help identify partners and negotiate terms for the drug-delivery platform (8/1) Power3 Medical Products Inc. (OTC BB:PWRM) University of Texas M.D. Anderson Cancer Center License agreement Power3 got rights to cancer technologies co-developed by the parties The technologies involve an early detection test, protein biomarkers and targets for drugresistant cancer (8/9) Power3 Medical Products Inc. (OTC BB:PWRM) The Methodist Agreement Hospital Research Institute To search for biomarkers and develop diagnostic tests for neurodegenerative diseases The deal marks a continuation of work already under way between the parties; terms were not disclosed (7/19) Prolexys Pharmaceuticals Inc.* Imperial College London Agreement Prolexys joined a consortium focused on developing drugs for treatment of latent tuberculosis infection The consortium is supported by a $20M grant to Imperial College from the Grand Challenges in Global Health initiative (7/28) RegeneRx Biopharmaceuticals Inc. (AMEX:RGN) Children’s National Medical Center Collaboration To study the effects of thymosin beta 4 to treat degenerative muscle diseases The center will test TB4 in nonhuman models that have a disease similar to human Duchenne’s muscular dystrophy and go on to develop cardiomyopathy (8/4) Rubicon Genomics Inc.* Genome Institute of Singapore Agreement Rubicon will isolate and amplify genomic DNA in archived serum samples The samples are from 5,000 participants in a hepatitis B vaccine trial; GIS will use the DNA to discover genes relevant to HBV (7/21) Saneron CCEL Therapeutics Inc.* University of Minnesota License agreement Saneron acquired rights to a cord blood cell line from the university The university is entitled to research funding and milestone payments; the technology will be used to develop cellular therapies for neurological and cardiac disorders (9/7) 338 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Sareum Holdings plc (UK; AIM:SAR) The Institute of Cancer Research and Cancer Research Technology Ltd. (both in the UK) Collaboration To develop cancer drugs that target a biochemical pathway responsible for resistance to standard chemotherapeutics Sareum will use its Template Screening technology to identify compounds; it would share in any payments, milestones and royalties arising from resulting license deals (7/25) Serologicals Corp. (SERO) Wisconsin Alumni Research Foundation License agreement Serologicals unit Chemicon International Inc. got nonexclusive rights to all WARF’s stem cell technologies Chemicon intends to commercialize research products derived from human embryonic stem cell technology; terms of the deal were not disclosed (7/25) SIGA Technologies Inc. (SIGA) Saint Louis University Agreement Deal for the continued development of SIGA’s smallpox candidate, SIGA-246 SIGA will get $1M to support preclinical development; the deal is funded through the National Institutes of Health (9/20) Structural GenomiX Inc.* Cystic Fibrosis Foundation Therapeutics Inc. Collaboration Three-year deal to discovery therapies to treat the cause of cystic fibrosis SGX will generate lead compounds that “correct” the delta F508 form of the CFTR protein; SGX gets $1 5M in technology access, research and milestone payments and is eligible for clinical milestone payments and royalties on sales (7/6) Targepeutics Inc.* National Institutes License of Health agreement Targepeutics licensed patents relevant to its genetically engineered interleukin-13 platform The 10 patents give background rights for the platform; terms of the deal were not disclosed (8/17) Tm Bioscience Corp. (Canada; TSE:TMC) University of Miami Supply agreement Tm will provide reagents to the university University researchers will use the technology in cystic fibrosis and Ashkenazi Jewish panel gene assays (7/27) TriPath Imaging Inc. (TPTH) Cancer Research Technology Ltd. (UK) License agreement TriPath got rigths to a number of cancer diagnostic markers The markers, from the Minichromosome Maintenance protein family, have applicability in various solid tumors (8/22) Unigene Laboratories Inc. (OTC BB:UGNE) Yale University Agreements Unigene acquired exclusive rights to jointly owned inventions The technology involves procedures for treating and preventing fractures more effectively; Unigene is sponsoring research at Yale (9/19) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 339 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) U.S. BioDefense Inc. (OTC BB:UBDE) University of British Columbia (Canada) License agreement Option deal covering UBC’s neural crest stem cell line and its use in human transplantation U.S. BioDefense got a six-month option to license worldwide rights to the patent; terms were not disclosed (7/6) Vical Inc. (VICL) National Institute Cooperative of Allergy and Research and Infectious Diseases Development Agreement To develop electroporation-enhanced delivery of DNA vaccines against HIV Vical has an option to get exclusive rights to technology developed under the CRADA (9/12) Vion Pharmaceuticals Inc. (VION) University of Innsbruck (Austria) License agreement Vion licensed a group of heterocyclic hydrazone compounds for cancer applications Vion will make an initial payment of $37,500 and could make milestone and royalty payments (9/26) Xenomics Inc. (OTC BB:XNOM) Lazzaro Spallanzani Institute (Italy) Agreement They created a joint venture, SpaXen, to research Xenomics’ diagnostic technology for detecting infectious disease Licensing terms and royalties were covered in the deal, terms of which were not disclosed; the deal centers on Xenomics’ Transrenal-DNA diagnostic technology (7/12) YM BioSciences Inc. (Canada; TSE:YM) University of Saskatchewan (Canada) License agreement YM got exclusive rights to a portfolio of small-molecule oncology compounds The compounds are believed to be highly potent chemopotentiators; terms were not disclosed (8/10) York Pharma plc (UK; AIM:YRK) Freie Universitat Berlin (Germany) Acquisition York acquired patents relating to sphingosine1-phosphate The preclinical technology may have applications in hyperproliferative skin disorders such as acne; the university gets an upfront payment and potential royalties (7/19) FOURTH QUARTER Acceptys Inc.* University of Wurzburg (Germany) Research agreement University researchers will further characterize about 650 anticancer human antibodies The deal followed one in which Accelerys acquired rights to develop antibodies from OncoMab GmbH, which was formed from university research (12/23) Accentia Biopharmaceuticals Inc. (ABPI) Mayo Foundation for Medical Education and Research Option agreement The option covers a method of using antifungals applied intranasally for treating chronic sinusitis Accentia has exclusive rights to negotiate a license until Dec. 6, 2006; the method covers all antifungals except amphotericin B (12/15) 340 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) ACE BioSciences A/S* (Denmark) Aeras Global TB Vaccine Foundation Collaboration ACE will support characterization of a BCG-based tuberculosis vaccine ACE will identify and characterize proteins in the second-generation vaccine Aeras is developing; terms were not disclosed (12/19) Affibody AB* (Sweden) National Cancer Institute Cooperative Research and Development Agreement Deal to develop in vivo imaging agents for detecting cancer The company will design and develop engineered Affibody molecules specific for HER2; terms were not disclosed (1 1/8) Affymetrix Inc. (AFFX) Imperial College London and the Medical Research Council (UK) Collaboration To discover genetic variations associated with cancer, diabetes and cardiovascular disease College and MRC researchers will use Affymetrix GeneChip technology in the deal, which is part of Affymetrix’s translational medicine program (12/14) Affymetrix Inc. (AFFX) CureSearch Children's Oncology Group Collaboration To discover and validate gene expression signatures for a number of childhood cancers They will use Affymetrix’s GeneChip microarray technology and COG’s databank of tumor samples in the effort (10/25) Affymetrix Inc. (AFFX) and CapitalBio Corp. (China) Chinese Rice Agreement Functional Genomic Research Consortium CapitalBio will provide Affymetrix GeneChip Rice Genome Array services to the consortium CapitalBio is an Affymetrix service provider in China; terms of the deal were not disclosed (10/10) Affymetrix Inc. (AFFX) Jeffrey Modell Collaboration Foundation and the National Human Genome Research Institute To develop newborn screening tests The tests will be for severe combined immunodeficiency and other primary immunodeficiency disorders; the foundation will fund the work (10/5) Aphios Corp.* Boston University Medical School License agreement Aphios got rights to a nontoxic vitamin D analogue The compound is being developed for prostate cancer; terms of the deal were not disclosed (12/13) Ariana Pharmaceuticals* (France) Institut Pasteur (France) Agreements Series of deals involving Ariana’s new virtual screening platform The institute gets an equity stake in Ariana, becomes a customer for Ariana’s technology and provides use of its BioTop incubator; specific terms were not disclosed (1 1/2) Artemis Pharmaceuticals GmbH (Germany; subsidiary of Exelixis Inc.; EXEL) Medical Research Council Protein Phosphorylation Unit (UK) License agreement Artemis got rights to use and distribute certain genetically engineered mouse models Artemis will distribute the kinase models to companies and institutions, and can use them in its programs; terms were not disclosed (12/5) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 341 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Avexa Ltd. (Australia; ASX:AVX) Product Area Details (Date) Commonwealth Collaboration Scientific and Industrial Research Organisation (Australia) Deal to discover drugs for treating viral diseases Avexa will screen CSIRO libraries and would develop any resulting compounds (1 1/9) Avidex Ltd.* (UK) King’s College London License agreement Avidex got exclusive rights to develop products recognizing an antigen associated with Type I diabetes Avidex intends to develop soluble monoclonal T-cell receptors targeting KCL’s antigen on the islet cells in the pancreas (10/10) BioVeris Corp. (BIOV) University of Massachusetts at Amherst License agreement BioVeris exercised its option to exclusively license a vaccine candidate for Chlamydia UMA gets a $75,000 license fee and potential milestone payments, as well as royalties on any resulting sales (12/6) BioVeris Corp. (BIOV) Jewish General Hospital (Canada) License agreement BioVeris got exclusive rights to use a JGH database containing infectious disease information The database has demographic data and the serologic status on an immigrant population; BioVeris paid a $50,000 license fee and will sponsor $400,000 of research at JGH over three years (1 1/21) CellCentric Ltd.* (UK) University College London Collaboration Deal to explore epigenetic-related cancer cell targets CellCentric will work with the university’s Wolfson Institute of Biomedical Research in the sponsored research program (1 1/1) Cel-Sci Corp. (AMEX:CVM) National Institute Cooperative of Allergy and agreement Infectious Diseases Deal to test Cel-Sci’s anti-infective drug CEL-1000 in animal models against the H5N1 avian flu virus The agent is believed to activate immune responses; terms of the deal were not disclosed (12/5) Ceragenix Pharmaceuticals Inc. (OTC BB:CGXP) Centers for Disease Control and Prevention Cooperative Research and Development Agreement Letter of intent calls for evaluation of company’s cationic steroid antimicrobial coating Focus is prevention of bacterial biofilm growth on medical devices; Brigham Young University also is a party to the CRADA (10/25) Chemokine Therapeutics Corp. (Canada; TSE:CTI) Wayne State University Agreement University researchers will conduct preclinical experiments on a Chemokine cancer drug The studies will evaluate the ability of CTCE-9908 to inhibit the CXCR4 receptor found on prostate cancer cells (1 1/16) Ciphergen Biosystems Inc. (CIPHE) University of Texas Medical Branch at Galveston Collaboration Deal to apply Ciphergen technologies to UTMB clinical samples for liver disease research They intend to develop a diagnostic blood test for measuring the progress of liver disease; Cipheregen gets first right to license resulting products (1 1/21) 342 Type Of Agreement BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions(Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Ciphergen Biosystems Inc. (CIPH) University College London Research and license agreement To further validate and characterize ovarian cancer biomarkers and discover new ones Ciphergen will have exclusive rights to license discoveries made during the collaboration (10/6) CombiMatrix Group (CBMX) University of California at Los Angeles Collaboration Deal to develop a genebased test for the diagnosis of malignant melanoma UCLA researchers also will provide patient samples for the development and validation phase of the project (12/7) Covalys Biosciences AG* (Switzerland) Ecole Polytechnique Fédérale de Lausanne (Switzerland) Agreement Covalys will exclusively commercialize the school’s ACP-tag technology Terms on the deal involving protein tag technology were not disclosed (1 1/7) Crucell NV (the Netherlands; CRXL) Walter Reed Army Institute of Research Cooperative Research and Development Agreement Deal to evaluate Crucell’s PER.C6 technology for development of vaccines against certain flaviviruses WRAIR will evaluate the technology in vaccines against dengue fever and Japanese encephalitis; terms were not disclosed (12/22) Crucell NV (the Netherlands; CRXL) Saskatchewan Research Council (Canada) Manufacturing agreement SRC got rights to sell PER.C6 cell line services in Canada; SRC also got a license to the technology The services are for manufacturing gene therapy and vaccine products; Crucell gets a license fee, annual maintenance fees and royalties on sales (12/22) Cygenics Ltd. (Australia; ASX:CYN) Johns Hopkins University Collaboration Deal to combine technologies in a preclinical program for acute myeloid leukemia The effort will use Cygenics’ stem cell expansion platform with Hopkins’ stem cell purging technology (1 1/15) CytRx Corp. (CYTR) University of Massachusetts Medical School Expanded agreement The new deal covers drug targets that regulate insulin activity in fat cells CytRx licensed the targets, which were discovered in an existing collaboration between it and UMMS (12/15) Dendritic Nanotechnologies Inc.* Nanotechnology Characterization Laboratory Collaboration The NCL will characterize DNT’s dendrimers as macromolecular dendrimer-based MRI contrast agents The agents will be used for cardiovascular diagnostics; the NCL was established by the National Cancer Institute (10/10) Dharmacon Inc. (unit of Fisher Biosciences) Various institutions Global initiative To advance research using a genome-wide siRNA library Dharmacon and 10 research institutions formed the GenomeWide RNAi Global Initiative (10/6) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 343 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit DiscoveRx Corp.* Product Area Details (Date) National Institutes Collaboration of Health DiscoveRx is providing access to its PathHunter technology for smallmolecule screening Molecules will be screened against targets of interest in the NIH’s Molecular Libraries Roadmap initiative (1 1/3) Exelixis Plant Sciences Inc. (unit of Exelixis Inc.; EXEL) Washington State University Research Foundation License agreement Exelixis will use its technologies to develop methods for producing paclitaxel and taxane intermediates Exelixis has advanced developments of its its taxane cell factory program under a previous license from WSURF; terms were not disclosed (12/28) 454 Life Sciences Corp. (majority owned by CuraGen Corp.; CRGN) The Broad Institute Collaboration The institute will conduct genomic studies relating to the genetic basis for complex diseases The institute will use a genome sequencer system from 454 in the effort; terms of the deal were not disclosed (12/19) Gammacan International Inc. (Israel; OTC BB:GCAN) Tel Hashomer Research Medical Research and license Infrastructure and agreement Services Ltd. (Israel) To explore mechanisms of action and uses in cancer treatment of IVIg Terms of the deal were not disclosed (12/20) Genentech Inc. (NYSE:DNA) Accelerate Brain Cancer Cure To explore Genentech’s Avastin for treating patients with glioblastoma multiforme ABC2 will share expenses in an imaging study and then would provide resources for a Genentech-sponsored trial (10/19) Genome Express* (France) Centre Léon Collaboration Bérard and Centre Jean Perrin (both in France) High-throughput sequencing program for the mutational analysis of 300 gene candidates in human cancers Results of the research will be made available to researchers; the Mutacancer program is being supported by France's National Cancer Institute (10/28) Genzyme Corp. (GENZ) University of California at Los Angeles License agreement Genzyme got exclusive diagnostic rights to gene mutations believed to be associated with resistance to Gleevec Genzyme intends to develop a test to detect many BCR-ABL mutations and monitor resistance in chronic myeloid leukemia patients (10/6) Hemispherx Biopharma Inc. (AMEX:HEB) Canadian Department of National Defence Research agreement To evaluate antiviral efficacy of the company’s Ampligen and Alferon products Defence R&D Canada is testing the products against influenza in an effort focused on the bird flu (1 1/29) Hemispherx Biopharma Inc. (AMEX:HEB) National Institute of Infectious Diseases (Japan) Research agreement The institute will evaluate Hemispherx’s Ampligen It will assess the product as an adjuvant to its nasal flu vaccine; terms were not disclosed (10/3) 344 Type Of Agreement Collaboration BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Humanetics Corp.* Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. License agreement Deal to develop the oral agent BIO300 for protecting the immune system against radiation exposure Humanetics assumed responsibility for continued testing, development and commercialization of the product; terms were not disclosed (12/8) Humanetics Corp.* Mount Sinai School of Medicine License agreement Humanetics got rights to NIC5-15, a preclinical agent being developed for Alzheimer’s disease They also agreed to a deal under which Mount Sinai will test the agent in humans; terms were not disclosed (12/1) Hybrigenics SA* (France) Genethon (France) Collaboration Genethon will use Hybrigenics technology in research in muscle cell proteins and their interaction Hybrigenics will use screening and protein interaction mapping software in the effort; Genethon will own resulting data; terms were not disclosed (12/21) Illumina Inc. (ILMN) Cancer Research UK Services agreement Illumina will conduct genotyping studies focused on colorectal cancer Illumina’s Sentrix Arrays and Infinium Assay will be used in the multimillion-dollar deal (1 1/8) Illumina Inc. (ILMN) Children’s Agreement Hospital Oakland Research Institute Illumina will provide reagents and instrumentation for a study by the institute The institute is studying the impact of single nucleotide polymorphisms on responses to statins under an NIH-funded program (10/20) Invitrogen Corp. (IVGN) Families of Spinal Muscular Atrophy Collaboration To identify targets linked to causes and symptoms of spinal muscular atrophy Invitrogen will use its protein microarray technology in the intial stages of the deal; terms were not disclosed (12/21) Invitrogen Corp. (IVGN) National Center for Drug Screening (China) Collaboration Deal focused on the high-throughput screening of compound libraries against nuclear receptors The center will use Invitrogen technologies in the effort; terms of the deal were not disclosed (10/31) Invitrogen Corp. (IVGN) Georgia Tech Research Corp. License agreement Invitrogen got exclusive rights to metal nanocluster technology The small, bright fluorescent particles may be useful in in vivo and in vitro applications (10/6) iQur Ltd.* (UK) University of Southampton License agreement iQur got rights to technology used for treating liver fibrosis Terms of the deal were not disclosed (1 1/8) Locus Pharmaceuticals Inc.* Cornell Research Foundation License agreement Locus licensed a second crystal structure of the fusion protein gp41 Locus intends to use the structure to design small-molecule inhibitors of HIV (1 1/15) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 345 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) MedImmune Inc. (MEDI) Burnham Institute for Medical Research License agreement Deal to develop peptides targeting the EphA and EphB subfamilies of receptor tyrosine kinases MedImmune would develop and market any resulting products; Burnham gets an up-front fee and potential milestone and royalty payments (12/8) MedImmune Inc. (MEDI) Mount Sinai School of Medicine License agreement MedImmune got exclusive rights to certain reverse genetics technology Mount Sinai gets an up-front fee and potential milestone and royalty payments; the technology will be used to improve the efficiency of producing new influenza vaccine strains (12/7) Memory Pharmaceuticals Corp. (MEMY) The Stanley Medical Research Institute Funding support The institute will help fund trials of Memory’s MEM 1003 for treating bipolar disorder The neuronal L-type calcium channel modulator is nearing Phase IIa trials in that indication; Memory is eligible to receive up to $3.2M in the deal (12/20) MerLion National Cancer Pharmaceuticals Institute Pte. Ltd.* (Singapore) Cooperative Research and Development Agreement To discover and develop small-molecule inhibitors of the hypoxic signaling pathway for treating cancers MerLion will perform initial screening of candidate molecules; each party may then further investigate and develop those candidates (10/18) Metabolon Inc.* University of Michigan Collaboration They will work to discover disease biomarkers for prostate cancer The deal marks Metabolon’s first project as part of the NCI’s Early Detection Research Network; the project is funded by an NCI grant (1 1/30) MicroIslet Inc. (AMEX:MII) Mayo Foundation for Medical Education and Research Supply agreement Mayo will supply pathogen-free pigs to MicroIslet for use in development of a product for diabetes Pig islets will be used in the MicroIslet-P product; MicroIslet also got rights to use the pigs for research and treatment in diabetes under the long-term deal (1 1/22) Morphotek Inc.* John Wayne Cancer Institute Collaboration Deal to discover and develop antibodies to a cancer-associated protein Morphotek will apply its Human Morphodoma technology to the protein discovered at JWCI (1 1/14) M-phasys GmbH* (Germany) Fraunhofer Institute (Germany) Collaboration Deal to discover monoclonal antibodies to GPCR cancer targets They will take resulting products through early preclinical testing, then offer them for licensing (1 1/14) 346 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) MultiCell Technologies Inc. (OTC BB:MCET) Columbia University Medical Center Research agreement Deal to perform in vivo tests on an agent for protecting against retinal ganglion cell death MultiCell will fund research and have an exclusive option to resulting discoveries; the focus is on ocular neurodegenerative diseases (12/1) MultiCell Technologies Inc. (OTC BB:MCET) Thomas Jefferson University Collaboration Deal to evaluate the The focus is their use as model company's immortalized systems to identify new drugs to human hepatocytes treat hepatitis C viral infection (10/20) NanoMed Pharmaceuticals Inc.* University of Kentucky Option agreement NanoMed will evaluate raspberry gels for treating and preventing oral epithelial dysplasia NanoMed intends to start trials in humans; Ohio State University also was a party to the exclusive option agreement (12/13) NovaThera Ltd.* (UK) Imperial College London and The Texas Heart Institute Collaboration They established a program to scale up supply of human heart cells for clinical trials Using bioprocessor technology, the group intends to develop processes for the practical manufacture of cells for medical uses (12/12) Novelix Pharmaceuticals Inc.* University of Southern California License agreement Novelix got exclusive rights to a group of potential cancer therapeutics The lead compound, NVX-144, is expected to enter clinical trials late in 2006; terms of the deal were not disclosed (12/19) Novelos Therapeutics Inc. (OTC BB:NVLT) Shriners Hospitals for Children Collaboration Deal to confirm findings in the therapy of acute radiation injury obtained in Russian experiments They also plan to more precisely identify the cellular and molecular actions of Novelo’s NOV-002 (1 1/8) Open Biosystems Inc.* Four cancer centers Agreement The centers adopted the company’s short hairpin RNA technology for use in cancer research Duke University, the National Cancer Institute, Lee Moffitt Cancer Center and Fox Chase Cancer Center adopted the technology (12/19) Peregrine Pharmaceuticals Inc. (PPHM) Sidney Kimmel Cancer Center Manufacturing agreement Peregrine subsidiary Avid Bioservices Inc. will perform manufacturing services for SKCC Avid will provide services related to an antibody initially being developed for lung cancer (12/22) Perlegen Sciences Inc.* and Affymetrix Inc. (AFFY) Wellcome Trust entities (UK) Collaboration To conduct wholegenome association studies to search for genes associated with 10 complex diseases Perlegen will genotype 15,000 individuals and produce more than 10 billion individual genotypes using Affymetrix technology; terms were not disclosed (10/5) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 347 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Phylogica Ltd. (Australia; ASX:PYC) University of Western Australia Research collaboration UWA will screen Phylogica’s library in an effort focused on phosphatases One project targets leukemia proteins and a second targets stroke; they will jointly own resulting technology (10/18) Phylogica Ltd. (Australia; ASX:PYC) Massachusetts License General Hospital agreement and Johns Hopkins University Phylogica gained access to genetic screening technology The technology augments the company’s drug discovery capabilities; terms were not disclosed (10/18) Prima Biomed Ltd. (Australia; ASX:PRR) Walter Reed Army Institute of Research Cooperative Research and Development Agreement Deal to include the DCtag vaccine adjuvant technology in the development of a malaria vaccine The deal was signed with Prima subsidiary Panvax Ltd. and the Austin Research Institute; Prima has rights to resulting technology (10/18) Reata Pharmaceuticals Inc.* National Cancer Institute Cooperative Research and Development Agreement Deal for the development of RTA 401 (CDDO), a synthetic triterpenoid Agent is a designed to induce programmed cell death in cancer cells by activating redox-sensitive signaling pathways (10/12) Santhera Pharmaceuticals AG* (Switzerland) National Institute of Neurological Disorders and Stroke Collaboration To evaluate Santhera’s SNT-MC17 (idebenone) in patients with Friedreich’s ataxia The NIH will run a Phase II trial in 48 patients (1 1/3) Savient Pharmaceuticals Inc. (SVNTE) University of California at San Diego License termination Savient ended a deal covering development of Prosaptide The decision was made following a failed Phase II trial in patients with HIV-associated peripheral neuropathy (12/22) Sequenom Inc. (SQNM) University of Oxford (UK) License agreement Sequenom acquired rights to non-invasive prenatal diagnostic technology Isis Innovation Ltd., the technology transfer company of the university, is entitled to up-front fees, milestone payments and royalties on any sales (10/20) Starpharma Holdings Ltd. (Australia; ASX:SPL) Biomolecular Amended Research Institute agreement Ltd. (Australia) Starpharma acquired outright ownership of technology that was shared when it was spun out of BRI in 1996 Starpharma also acquired the 25% royalty that would be due to BRI; the technology forms the basis for its VivaGel microbicide product; BRI got 7.1M Starpharma shares (10/1 1) Stem Cell Sciences plc (UK; AIM:STEM) University of Nice (France) Stem Cell got rights to human multipotent adipose-derived stem cells and technologies Stem Cells will use the technology to develop cell therapies for degenerative diseases; the university is entitled to up-front fees and milestone and royalty payments (1 1/15) 348 License agreement BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Collaborations Between Biotechnology Companies And Universities/Nonprofit Institutions (Continued) Company* (Symbol) University/ Nonprofit Type Of Agreement Product Area Details (Date) Transgene SA (France; Eurolist: FR0005175080) International AIDS Vaccine Initiative Manufacturing agreement Transgene will manufacture an AIDS vaccine candidate for use in clinical trials Transgene will use its viral vectors process in the effort; terms of the 18-month contract were not disclosed (1 1/17) 20/20 GeneSystems Inc.* University of Kentucky License agreement 20/20 got rights to a a blood test for nonsmall-cell lung cancer 20/20 intends to create a screening test for the early detection of lung cancer based on biomarkers identified by UK (12/15) U.S. BioDefense Inc. (OTC BB:UBDE) National Institutes Agreement of Health Deal focused on USBD’s universal viral inactivation method The company said it is evaluating the technology with the NIH; details were not disclosed (1 1/15) Viragen Inc. (AMEX:VRA) Roslin Institute (UK) Renewed agreement They are working on avian transgenic technology as a biomanufacturing platform They now are evaluating two candidates that already are on the market; terms were not disclosed (1 1/1) Viropro Inc.* (Canada; OTC BB: VPRO) Biotechnology Research Institute (Canada) Collaboration Deal to develop production procedures for biological materials and drugs The intent is to market recombinant proteins and a new vaccination platform (12/1) Xechem International Inc. (OTC BB:XKEM) Virginia Commonwealth University License agreement Xechem got rights to a five-membered heterocyclic anti-sickling compound The compound will be studied for treating sickle cell disease; terms of the exclusive license were not disclosed (12/9) Xencor Inc.* University of Cambridge (UK) License agreement Xencor got rights to technology for creating monoclonal antibodies with enhanced potency The technology includes specific Fc variants that complement Xencor's XmAb engineered Fc domains; terms of the exclusive deal were not disclosed (12/14) Notes: This chart does not include grants or contract awards, or agreements between biotech companies and clinical trial centers. * Denotes privately held company. @ Some institutions listed have for-profit components. They are located in the U.S. unless otherwise noted. Unless otherwise noted, shares are traded on the Nasdaq exchange. AIM = Alternative Investment Market; AMEX = American Stock Exchange; ASX = Australian Stock Exchange; CDNX = Canadian Venture Exchange; LSE = London Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; PK = Pink Sheets; TSE = Toronto Stock Exchange; VSE = Vienna Stock Exchange. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 349 2005 Deals, Other Actions in Agriculture and Animals Biotech Co.* (Country; Symbol) Agbiotech Partner (Country; Symbol) Type/Product Area Terms/Details (Date) AgraQuest Inc.* U.S. Department of Agriculture AgraQuest was awarded a Phase II Small Business Innovation Research grant for development of a biological fumigant The two-year, $296,000 grant wil be used for a product based on the fungus Muscodor albus that is expected to have multiple applications in post-harvest and soil-borne diseases (1/4) ArrayXpress Inc.* North Carolina Biotechnology Center The center awarded ArrayXpress a $150,000 research loan ArrayXpress will use the loan to develop a diagnostic test for a swine disease (3/8) Arysta LifeScience Corp.* (Japan) Bayer CropScience (unit of Bayer AG) They entered agreements that expand existing collaboration Arysta acquired amitraz (Mitac), an araricide and insecticide; got a license to market the fungicide fluoxastrobin in certain areas; and got a license to co-market deltamethrin, a pyrethroid insecticide, in the U.S. (4/27) Athenix Corp.* Iowa Corn Promotion Board Research cooperation to explore opportunities of applying innovative technologies to corn The board partnered with Athenix on the work under undisclosed terms (2/17) Arcadia Biosciences Inc.* National Institutes of Health Arcadia received a grant to develop soybeans with desired levels of soy isoflavones Arcadia will use its Tilling screening technology in the effort; terms of the grant were not disclosed (10/31) Arcadia Biosciences Inc.* and Washington State University National Institutes of Health Arcadia and WSU received a Small Business Technology Transfer grant related to research on wheat They will research lines of wheat with reduced celiac disease-causing proteins (10/5) Arcadia Biosciences Inc.* Monsanto Co. Monsanto licensed rights to use Arcadia’s nitrogen use efficiency technology in canola Arcadia is entitled to an up-front payment and potential milestone and royalty payments in the deal; Monsanto gets global rights (9/20) Avidis SA* (France) Merial Ltd. (joint venture of Merck & Co. Inc. and Sanofi-Aventis) Merial got rights to use Avidis’ aXent technology to develop recombinant veterinary vaccines aXent is an adjuvant-free immunization technology; the agreement covers the use of aXent for two infectious diseases (1 1/30) BioDiem Ltd.* (Australia) Australian Industry Department BioDiem was awarded an A$2M ($1.5M) grant for research on its antimicrobial compound BDM-1 The AusIndustry Commercial Ready grant will support testing of the product as a potential replacement for antibiotics in the poultry industry (12/21) 350 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology-Agribusiness Collaborations (Continued) Biotech Co.* (Country; Symbol) Agbiotech Partner (Country; Symbol) Type/Product Area Terms/Details (Date) Chlorogen Inc.* Dow AgroSciences LLC They entered deals to use chloroplast transformation technology in Dow’s animal health and agricultural biotechnology businesses The technology is used for expressing foreign genes in plant cells; one deal focuses on animal health vaccines; the other is on expressing Dow’s traits in agricultural crops; terms were not disclosed (9/16) Chromatin Inc.* University of Illinois at Urbana-Champaign They launched a program to accelerate development of mini-chromosome technology for the delivery of multiple traits in corn The partnership leverages expertise in corn breeding and genetics at the university and Chromatin’s mini-chromosome technology for improving characteristics in corn; terms were not disclosed (2/8) CompleGen Inc.* DuPont Crop Protection CompleGen will use its XenoGene system to discover the targets of active compounds identified by DuPont XenoGene uses a reverse chemical genomics approach; it is the fourth deal between the companies; terms were not disclosed (5/1 1) Crucell NV (the Netherlands; CRXL) Merial Ltd. (joint venture of Merck & Co. Inc. and Sanofi Aventis) Nonexclusive deal allows Merial to use the PER.C6 cell line for developing a gene therapy in a specific field of companion animal medicine The deal, which is the second between the companies, includes an option for a commercial license agreement; terms were not disclosed (12/22) Cryptome Dairy Pharmaceuticals Australia Ltd. (Australia; ASX:CRP) Three-year deal on research to discover pharmaceuticals and nutraceuticals in milk proteins Dairy Australia is supporting work at Cryptome to identify and characterize proteins and fragments of proteins with potential health benefits (1 1/9) CytImmune Sciences Inc.* Boehringer Ingelheim Animal Health (Germany) BI licensed rights to use CytImmune’s drug delivery technology for veterinary applications The technology will be applied to development of tumor-targeted cancer drugs for the veterinary market; terms were not disclosed (2/16) Cytos Biotechnology AG (Switzerland; SWX:CYTN) Pfizer Inc. Pfizer entered an option agreement on two Cytos Immunodrug products for animal health applications Pfizer also has first right to negotiate on other products for animal health; Cytos gets an up-front payment and potential milestone and royalty payments (1/6) Evogene Ltd.* (Israel) Faculty of Agriculture at Hebrew University (Israel) Collaboration to jointly develop tomato varieties with improved taste and aroma They will pool technologies and expertise in the effort, terms of which were not disclosed (5/24) Exelixis Inc. (EXEL) GenOptera LLC (joint venture of Exelixis and Bayer CropScience) They are ending early a venture formed in 2000 to develop insecticides; Bayer is acquiring Exelixis’ 40% stake in GenOptera Bayer will have rights to resulting discoveries in agriculture; Exelixis will have rights in all other fields; Exelixis will get an early termination fee of about $10.9M (4/1) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 351 2005 Biotechnology-Agribusiness Collaborations (Continued) Biotech Co.* (Country; Symbol) Agbiotech Partner (Country; Symbol) Type/Product Area Terms/Details (Date) 454 Life Sciences Corp. (majority owned by CuraGen Corp.; CRGN) National Center for Genome Resources 454 was selected to sequence the major pathogen of vegetable crops, Phytophthora capsici 454 and the NCGR will work with the Joint Genome Institute of the Department of Energy, Ohio State University and the University of Tennessee in the collaboration (12/14) Genaissance Biotronics Ltd. Pharmaceuticals (Cyprus) Inc. (GNSC) Genaissance will provide high-throughput genotyping services to Biotronics Biotronics is working under a government contract to establish a breeding program in sheep that confers resistance to scrapie (8/23) Genaissance Hellenic Ministry Pharmaceuticals of Rural DevelopInc. (GNSC) ment and Food (Greece) Genaissance will provide high-throughput sample handling and genotyping services The work under a deal with Antisel A. Selidis Bros. SA is for establishing a breeding program in sheep that confers resistance to scrapie (8/1 1) Genaissance Monsanto Co. Pharmaceuticals and the Inc. (GNSC) Agricultural Research Service Collaboration to develop technology for more accurate and efficient soybean breeding The firms and the USDA’s ARS will map the genome of the soybean and make the data publicly available; terms of the deal were not disclosed (3/9) GangaGen Life Sciences Inc.* (Canada) Elanco Animal Health (unit of Eli Lilly and Co.) Deal to jointly develop and sell phage-based products for the control of dangerous bacteria A goal of the project is to eliminate pathogenic E. coli in cattle before the animal is processed for food; terms of the deal were not disclosed (9/14) Genedata AG* (Switzerland) Bayer CropScience (unit of Bayer AG) They extended for three years a collaboration in agrochemical research The deal includes licenses for the AgroLead edition of Genedata Phylosopher as well as for Genedata Expressionist technology (6/9) GeoPharma Inc. (GORX) Dechra Pharmaceuticals plc (UK) Worldwide marketing deal on GeoPharma’s levothyroxine liquid and tablets for animal health applications GeoPharma subsidiary Belcher Pharmaceuticals gets a $500,000 up-front payment; they will equally share profits from the product, which is used to treat hypothyroidism in dogs (2/17) Icoria Inc. (ICOR) Monsanto Co. Monsanto acquired Icoria assets related to the field of transgenic traits for agriculture applications Icoria gets $6.75M in cash, undisclosed installment and milestone payments, plus additional considerations; the companies have been researching the area for six years under an existing deal; a number of Icoria employees will join Monsanto (3/24) Icoria Inc. (ICOR) DuPont Crop Protection Icoria will screen a DuPont chemical library to identify compounds that improve crop productivity The goal is to increase nutrient uptake and tolerance to environmental stress; Icoria gets an undisclosed up-front payment and potential milestone and royalty payments (2/1) 352 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology-Agribusiness Collaborations (Continued) Biotech Co.* (Country; Symbol) Agbiotech Partner (Country; Symbol) Type/Product Area Terms/Details (Date) IDEXX Laboratories Inc. (IDXX) European Commission The company’s HerdChek test for postmortem detection of bovine spongiform encephalopathy was approved in Europe The EIA test uses Seprion ligand technology from Microsens Biotechnologies Ltd.; approvals in individual countries were expected to follow (2/18) iDiverse Inc.* University of Nebraska at Lincoln iDiverse licensed exclusive rights to UNL’s transgenic plant technology; they also agreed to collaborate on development The technology may provide plants with resistance to a range of diseases and environmental stresses; terms of the deal were not disclosed (7/20) Large Scale Biology Corp. (LSBC) Growers Research Group LLC GRG licensed rights to use LSBC’s Geneware plant gene expression technology GRG, a company whose members are a consortium of California agribusiness concerns, plans to discover new approaches to crop protection under the exclusive, worldwide research license; it also has an option to gain commercial rights (1 1/22) Lynx Therapeutics Inc. (merged with Solexa Ltd.; UK; SLXA) U.S. Department of Agriculture Lynx’s Massively Parallel Signature Sequencing technology will be used in a project focused on small RNAs in rice University of Delaware faculty members got a grant for the work from the USDA; resulting data will be made publicly available (2/24) Lynx Therapeutics Inc. (merged with Solexa Ltd.; UK; SLXA) National Science Foundation Lynx will provide genomewide transcriptome sequencing services on oyster samples The work is being done under a research grant the NSF awarded to University of Southern California researchers for work on genetics and physiology of oysters (1/31) Meridian Bioscience Inc. (VIVO) Synbiotics Corp. Deal under which Synbiotics will distribute the veterinary products of Meridian subsidiary Viral Antigens Inc. Synbiotics immediately began marketing VAI’s line of pseudorabies virus antibody test kits; they intend to explore additional veterinary diagnostic product opportunities (3/16) MerLion Dow Pharmaceuticals AgroSciences Pte. Ltd.* LLC (Singapore) Collaboration to identify candidates for new agrochemical agents MerLion brings its collection of natural product samples, natural product chemistry and bioprocessing expertise to the collaboration, terms of which were not disclosed (3/17) Modular Genetics Inc.* Three-year deal under which Monsanto gained an exclusive license to use MGI’s protein optimization platform in agricultural applications The deal includes the establishment of a research facility in Cambridge, Mass., where business and research headquarters will be relocated; terms of the deal were not disclosed (3/14) Monsanto Co. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 353 2005 Biotechnology-Agribusiness Collaborations (Continued) Biotech Co.* (Country; Symbol) Agbiotech Partner (Country; Symbol) Type/Product Area Terms/Details (Date) ParAllele BioScience (acquired by Affymetrix Inc.; AFFX) Dairy Cooperative Research Centre (Australia) Collaboration to screen the DNA of more than 1,500 elite Australian dairy bulls Technology from ParAllele and Affymetrix will be used for a high-density genomewide scan; terms of the deal were not disclosed (1 1/9) PRB Vietnam Pharmaceuticals Department of Inc.* and Lee’s Animal Health Pharmaceuticals Holdings Ltd. (Hong Kong) Vietnam officials will test an animal version of PRB’s antiviral product on their poultry flocks The effort is part of a multinational avian influenza research collaboration that includes institutions in Hong Kong, China and Thailand (7/8) PR Merial Ltd. Pharmaceuticals (joint venture of Inc.* Merck and Co. Inc. and Sanofi-Aventis Group) Collaboration to develop animal health products using PRP’s sustained-release formulation and manufacturing technologies Merial has exclusive rights to resulting products; terms were not disclosed; Merial already distributes PRP’s DuraLease product to the North American beef industry (3/16) Perlegen Sciences Inc.* International Rice Research Institute (the Philippines) Collaboration to identify DNA variation in 15 rice strains Perlegen will use its high-throughput oligonucleotide array approach enabled by Affymetrix Inc. GeneChip technology in the effort; terms were not disclosed (1 1/16) Sangamo BioSciences Inc. (SGMO) Dow AgroSciences LLC Dow got rights to access Sangamo’s zinc finger DNAbinding protein technology for use in plants and plant cell cultures The deal is exclusive in plant agriculture and industrial products, and nonexclusive in animal health and biopharmaceutical products produced in plants; Sangamo could get $27.5M in the first three years of the deal and up to $53M overall, plus milestone and royalty payments (10/5) Scynexis Inc.* Merial Ltd. (joint venture of Merck and Co. Inc. and Sanofi-Aventis Group) Collaboration under which Scynexis will be the primary animal health discovery research partner for Merial The agreement could run up to 15 years and be worth up to $150M for Scynexis, which also could get milestone payments and sales royalties in the deal (9/29) Sequenom Inc. (SQNM) GeneSeek Inc.* GeneSeek purchased Sequenom’s MassARRAY genetic analysis system GeneSeek will use the system for animal diagnostic testing, traceability and contract research and development (12/19) Sequenom Inc. (SQNM) MetaMorphix Inc.* MMI will use use Sequenom’s MassARRAY technology in field trials of DNA-based animal predictive diagnostic tools The deal supports an agreement MMI has with Cargill Inc.; the effort with Sequenom focuses on DNA screening and selection in livestock and companion animals (1 1/7) 354 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology-Agribusiness Collaborations (Continued) Biotech Co.* (Country; Symbol) Agbiotech Partner (Country; Symbol) Type/Product Area Terms/Details (Date) Sygen International plc (UK; LSE:SNI) Genus plc (UK; AIM:GNS) They reached an agreement under which Genus would acquire Sygen for £187M ($322M) in cash Sygen applies quantitative genetics and biotechnology to animal breeding; Genus focuses on bovine genetics (10/28) Xpention Genetics Inc.* University of Texas M.D. Anderson Cancer Center Xpention got exclusive rights to technology for detecting cancer based on the p65 tumor marker Xpention initially plans to use the technology to develop an immunological test for detecting cancer in canines; the technology also has applicability in humans; Xpention would pay royalties on resulting sales (4/27) Vical Inc. (VICL) Aqua Health Ltd. (Canada; affiliate of Novartis Animal Health) Aqua Health got approval in Canada to market a vaccine for farm-raised salmon The APEX-IHN vaccine, based on Vical’s plasmid DNA delivery technology, was approved for use against infectious hematopoietic necrosis virus (7/19) Notes: This chart contains information on new and revised corporate agreements, as well as other actions, involving agricultural or animal biotechnology. * Private companies are indicated with an asterisk. Unless otherwise indicated, shares are traded on the Nasdaq exchange. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 355 BIOWORLD ® B I O T E C H P R O D U C T DEVELOPMENT Who’s To Blame For Fewer Approvals: FDA Or Biotech? By Aaron Lorenzo Washington Editor WASHINGTON – The FDA approved fewer drugs last year than in 2004 – by some estimates a downturn of about a third or more – leaving industry observers wondering why. Perhaps it’s a more conservative stance at the FDA. “That’s what some people think,” said Michael Werner, who heads The Werner Group, a Washington-based consulting firm, “and it’s one of those things that once people start thinking that way, it sort of becomes true.” Or maybe it’s a drug industry that is drying up. Said Scott Gottlieb, the agency’s deputy commissioner for medical and scientific affairs, “There’s a decline in research productivity” at drugmakers, even though research and development spending “continues to grow at a rapid pace.” Talking late last year to members of PhRMA, he called such a disconnect “unsustainable” and implored the industry to move toward “approaches that increase the use of mechanistic data in preclinical and clinical research” to target new medicines to patients “likely to experience more of the benefits and fewer of the side effects.” More to the point, he said drug developers should begin to relay on new technologies in designing therapies, and they will get the FDA’s support in the process. Vera Hassner Sharav, president of the Alliance for Human Research Protection in New York, also blamed drug developers. “Part of the reason for the void,” she said, “is that the drug industry has set its vision on only the immediate profits. They didn’t plan ahead; it’s short-sightedness.” Sharav added that the industry is wrong in claiming that the FDA “is blocking the gates,” and added that there “are no decent drugs in the pipeline.” Werner disagreed, noting there are numerous biotech products “out there in late-stage clinical development.” The debate rages on. BioWorld Snapshots show there were 19 new drugs approved for biotech companies, four biotech-derived new chemical entities cleared for big pharma companies and 10 supplemental indications approved by the FDA. That compares to 26 new drug approvals from the BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 359 FDA in 2004 but does not include supplemental approvals or pharma approvals for biotech-derived drugs. The 2005 figure also is notably lower than 2003’s 23 and 2002’s 26 biotech approvals. Among the biotech drugs approved last year was BiDil (isosorbide dinitrate/hydralazine hydrochloride, from NitroMed Inc.), a combination product notable for its heart failure label specific to black patients. In the oncology space, Celgene Corp.’s Revlimid (lenalidomide) was approved for myelodysplastic syndromes. Partners Onyx Pharmaceuticals Inc. and Bayer Pharmaceuticals Corp. received clearance for Nexavar (sorafenib) in advanced renal-cell carcinoma. Savient Pharmaceuticals Inc.’s Soltamox, an oral liquid solution of tamoxifen, was approved for treating breast cancer in adjuvant and metastatic settings, and Abraxane (nanoparticle albumin-bound paclitaxel) from American Pharmaceutical Partners Inc. was cleared for use after failure of chemotherapy in metastatic breast cancer. Two closely interwoven growth hormone products won approval: Increlex (mecasermin, from Tercica Inc.) for growth failure due to primary IGFD, and iPlex (mecasermin rinfabate, from Insmed Inc.) for growth failure in children with severe primary IGF-1 deficiency, or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone. Both products have orphan drug designation by the FDA, and Tercica is suing Insmed for patent infringement. BioMarin Pharmaceuticals Inc.’s enzyme-replacement therapy Naglazyme (galsulfase) was approved for mucopolysaccharidosis VI, or Maroteaux-Lamy syndrome, a rare genetic disease that causes a deficiency of an enzyme needed for breaking down sugar. Two new diabetes products from Amylin Pharmaceuticals were approved: Byetta (exenatide) for the adjunctive treatment of Type II mellitus and Symlin (pramlintide) for Type I and II diabetes. The former is partnered with Eli Lilly and Co. Another Type II diabetes treatment, once-daily, extended-release Glumetza (metformin), was approved for Depomed Inc., which also got Proquin XR’s (ciprofloxacin) approval for uncomplicated urinary tract infections. Nastech Pharmaceutical Co. Inc.’s Nascobal (cyanocobalamin) nasal spray won approval for vitamin B-12 deficiency, and Unigene Laboratories Inc.’s Fortical (calcitonin-salmon, rDNA origin) nasal spray was cleared for 360 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 postmenopausal osteoporosis. In the ocular arena, ISTA Pharmaceuticals Inc.’s Xibrom (bromfenac sodium ophthalmic solution) was cleared for treating ocular inflammation following cataract surgery. Two identical counterterrorism products received approval for treating adverse reactions to smallpox vaccination: vaccinia immune globulin, from DVC LLC and CanGene Corp. DVC, formerly known as DynPort Vaccine Co., is under contract to sell its product, called VIGIV, to the Department of Defense, and CanGene has a contract to sell its drug, VIG, to the Department of Health and Human Services. Halozyme Therapeutics Inc. received a pair of approvals: Hylenex (rhHyaluronidase) for adjuvant use to increase the absorption and dispersion of other injected drugs, and Cumulase (rhHyaluronidase) for treating oocytes to facilitate certain in vitro fertilization procedures. That’s an impressive list, a sign, Werner said, of a maturing biotech sector. “There are many promising products in the pipeline, and there are also new uses of currently marketed products,” he said. Approvals By Big Pharma; Expanded Indications Several large pharmaceutical firms also received approvals for new chemical entities using biotech methods, including Bristol-Myers Squibb Co.’s Baraclude (entecavir) for chronic hepatitis B infections and Orencia (abatacept) for rheumatoid arthritis, as well as Boehringer Ingelheim’s Aptivus (tipranavir) for HIV-1 infections. Also, a number of already-approved drugs received supplemental approvals to broaden their usages and indications. They included Tarceva (erlotinib), from OSI Pharmaceuticals Inc. and Genentech Inc., for use with gemcitabine for treating advanced pancreatic cancer; Millennium Pharmaceuticals Inc.’s Velcade (bortezomib) was expanded for multiple myeloma patients who have received at least one prior therapy; Centocor Inc.’s Remicade (infliximab) received an expanded label to include ulcerative colitis and for reducing the signs and symptoms of active arthritis in patients with psoriatic arthritis; Amgen Inc.’s Enbrel (etanercept) now has a broadened indication in psoriatic arthritis, including improving physical function; Orphan Medical Inc.’s Xyrem (sodium oxybate) received supplemental approval for excessive daytime sleepiness associated with narcolepsy; Genentech Inc.’s Nutropin (somatropin [rDNA origin] for injection) and BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 361 Nutropin AQ got supplemental clearances for the long-term treatment of idiopathic short stature; The Medicines Co.’s anticoagulant Angiomax (bivalirudin) expanded its label to include patients undergoing percutaneous coronary intervention; and a new formulation of the osteoporosis drug Boniva (ibandronate) was cleared for partners F. Hoffmann-La Roche Ltd. and GlaxoSmithKline plc. ■ 362 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products Approved By The FDA In 2005 Company* (Symbol) Product Amgen Inc. (AMGN) and Wyeth Description Indication Action/Date Enbrel Etanercept; anti-tumor (FDA-approved) necrosis factor-alpha antibody Psoriatic arthritis The FDA approved an expanded indication, to improve physical function in PA patients; it was approved for treating PA in 2002 (6/1) American Pharmaceutical Partners Inc. (APPX) Abraxane Paclitaxel protein-bound particles for injection; albumin-bound Metastatic breast cancer The FDA approved the drug for use after failure of chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy (1/8) Amylin Pharmaceuticals Inc. (AMLN) and Eli Lilly and Co. Byetta Exenatide; Incretin mimetic Type II diabetes The FDA approved the drug as an adjunctive therapy to improve blood sugar control in patients not achieving adequate control on metformin and/or a sulfonylurea (4/29) Amylin Pharmaceuticals Inc. (AMLN) Symlin Pramlintide acetate; an analogue of human amylin Types I and II diabetes The FDA approved the drug for use with insulin in patients who failed to achieve desired glucose control with insulin (3/16) BioMarin Pharmaceutical Inc. (BMRN) Naglazyme Galsulfase; an enzyme replacement therapy Mucopolysaccharidosis-VI The FDA approved the drug, which has orphan status in the U.S. (6/1) Cangene Corp. (Canada; TSE:CNJ) VIG Vaccinia immune globulin For use in smallpox vaccinations The FDA approved the product for use in counteracting certain adverse reactions to smallpox vaccination (5/4) Celgene Corp. (CELG) Revlimid Lenalidomide; derivative of Thalomid (thalidomide) Myelodysplastic syndromes The FDA approved the product for treating transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality (12/28) Centocor Inc. (unit of Johnson & Johnson) Remicade Infliximab; monoclonal (FDA-approved) antibody that targets tumor necrosis factor-alpha Psoriatic arthritis The FDA approved the drug to reduce the signs and symptoms of active arthritis in patients with PA (5/17) Centocor Inc. (unit of Johnson & Johnson) Remicade Infliximab; monoclonal (FDA-approved) antibody that targets tumor necrosis factor-alpha Ulcerative colitis The FDA approved the product for treating ulcerative colitis (9/16) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 363 Biotechnology Products Approved By FDA In 2005 Company* (Symbol) Product Description Indication Action/Date Depomed Inc. (DEPO) and Biovail Corp. (Canada) Glumetza Once-daily, extendedrelease formulation of metformin hydrochloride Type II diabetes The FDA approved the product (6/3) Depomed Inc. (DEPO) Proquin XR Once-daily, extendedrelease formulation of ciprofloxacin hydrochloride Uncomplicated urinary tract infections The FDA approved the product in that indication (5/20) DVC LLC (unit of Computer Sciences Corp.) VIGIV Intravenous vaccinia immune globulin Side effects of smallpox vaccine The FDA approved the product for treating adverse reactions to smallpox vaccination (2/22) Genentech Inc. (NYSE:DNA) Nutropin and Nutropin AQ (both FDAapproved) Somatropin for injection Idiopathic short stature The FDA approved supplemental applications for the long-term treatment of ISS (7/7) Halozyme Therapeutics Inc. (AMEX:HTI) Cumulase Ex vivo formulation of recombinant human PH20 hyaluronidase Treatment of oocytes Received 510(k) clearance from the FDA for treating oocytes to facilitate certain in vitro fertilization procedures (4/19) Halozyme Therapeutics Inc. (AMEX:HTI) Hylenex (formerly Enhanze SC) Formulation of recombinant human hyaluronidase For use as a spreading agent The FDA approved the product for use as an adjuvant agent to increase the absorption and dispersion of other injected drugs; Baxter Healthcare Corp. will market the product (12/5) Insmed Inc. (INSM) iPlex (SomatoKine) Composition of insulin-like Severe growth factor-1 and its primary IGF-1 primary binding protein, BP3 deficiency The FDA approved the product for treating growth failure in children with severe primary IGF-1 deficiency (12/12) ISTA Pharmaceuticals Inc. (ISTA) Xibrom Bromfenac sodium solution; topical nonsteroidal anti-inflammatory agent Ocular inflammation following cataract surgery The FDA approved the product (3/28) Millennium Pharmaceuticals Inc. (MLNM) Velcade Bortezomib; proteasome (FDA-approved) inhibitor Multiple myeloma The FDA approved supplemental NDA to include the treatment of patients who have received at least one prior therapy (3/25) Nastech Pharmaceutical Co. Inc. (NSTK) Nascobal Vitamin B-12 deficiency The FDA approved the product; Questcor Pharmaceuticals Inc. has worldwide marketing rights (2/1) 364 Nasally delivered formulation of cyanocobalamin BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products Approved By FDA In 2005 Company* (Symbol) Product Description Indication Action/Date NitroMed Inc. (NTMD) BiDil Nitric oxide-enhancing oral agent; combination of isosorbide dinitrate and hydralazine Heart failure in AfricanAmericans The FDA approved the drug (6/23) Onyx Pharmaceuticals Inc. (ONXX) and Bayer Pharmaceuticals Corp. Nexavar (sorafenib) RAF kinase and VEGF inhibitor Advanced renal-cell carcinoma The FDA approved the product for treating advanced kidney cancer (12/20) Orphan Medical Inc. (unit of Jazz Pharmaceuticals Inc.*) Xyrem Sodium oxybate oral (FDA-approved) solution Narcolepsy The product gained FDA approval for treating excessive daytime sleepiness in patients with narcolepsy (1 1/22) OSI Pharmaceuticals Inc. (OSIP) and Genentech Inc. (NYSE:DNA) Tarceva Erlotinib HCl; small(FDA-approved) molecule HER1/EGFR inhibitor Advanced pancreatic cancer The FDA approved supplemental filing for use with gemcitabine in patients with advanced disease who have not received previous chemotherapy (1 1/3) Savient Pharmaceuticals Inc. (SVNTE) Soltamox Tamoxifen oral liquid solution Breast cancer The FDA approved the product for use in adjuvant and metastatic settings and to reduce risks of breast cancer under certain conditions (10/31) Tercica Inc. (TRCA) Increlex Mecasermin injection; recombinant human insulin-like growth factor-1 Short stature caused by IGF deficiency The FDA approved the drug for long-term treatment of growth failure in children with severe primary IGF-1 deficiency or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone (8/31) The Medicines Co. (MDCO) Angiomax Bivalirudin; direct thrombin (FDA-approved) inhibitor Anticoagulant The FDA expanded the label to include patients undergoing percutaneous coronary intervention (6/15) Unigene Laboratories Inc. (OTC BB:UGNE) Fortical Osteoporosis The FDA approved the product for treating postmenopausal osteoporosis; Upsher-Smith Laboratories Inc. will market it (8/15) A nasal calcitonin product BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 365 Biotechnology Products Approved By FDA In 2005 Notes: * Privately held Unless otherwise noted, the stock symbols listed for public companies are on the Nasdaq market. AMEX = American Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; TSE = Toronto Stock Exchange. 366 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) Actelion Ltd. Tracleer Actelion Ltd. Pulmonary arterial hypertension (1 1/01) Actelion Ltd. and Celltech Group plc Zavesca Actelion Ltd. Type I Gaucher’s disease (8/03) Advanced Tissue Sciences Inc. Dermagraft Smith & Nephew plc Chronic foot ulcers in diabetic patients (10/01) Agouron Pharmaceuticals Inc. (acquired by Warner-Lambert Co.) Viracept GlaxoSmithKline plc; F. Hoffmann-La Roche Ltd. HIV protease inhibitor (3/97); twice-daily dosing for HIV (12/99) Alkermes Inc. Risperdal Consta Johnson & Johnson Approved for treating schizophrenia (10/03) Alliance Pharmaceutical Corp. Imagent Alliance Pharmaceutical To provide anatomical information about the heart not Corp., Cardinal Health obtainable using echocardiography alone (6/02) Inc. and inChord Communications Inc. Alpha AlphaNine SD Alpha Therapeutic Corp. To prevent and control bleeding due to Factor IX deficiency associated with hemophilia B (7/96) Therapeutic Corp. (acquired by Baxter Healthcare Corp.) Aralast Baxter Healthcare Corp. Congenital deficiency of alpha-1 proteinase inhibitor and clinically evident emphysema (1/03) Alza Corp. (subsidiary of Johnson & Johnson) Doxil Alza Corp. Refractory ovarian cancer (6/99) Amgen Inc. (also, see Immunex Corp.) Aranesp Amgen Inc. Anemia associated with chronic renal failure (9/01); for chemotherapy-induced anemia in patients with nonmyeloid malignancies (7/02) Epogen Amgen Inc. Treatment of anemia associated with chronic renal failure and anemia in Retrovir-treated HIV-infected patients (6/89); anemia caused by chemotherapy in patients with non-myeloid malignancies (4/93) Infergen Amgen Inc.; Yamanouchi Consensus alpha interferon for hepatitis C (10/97) Pharmaceutical Co. Ltd. Kepivance Amgen Inc. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 For severe oral mucositis in patients with blood cancers who are undergoing high-dose chemotherapy followed by a bone marrow transplant (12/04) 367 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) Amgen Inc. Kineret Amgen Inc. Rheumatoid arthritis (1 1/01) Neulasta Amgen Inc. Chemotherapy-induced neutropenia (2/02) Neupogen F. Hoffmann-La Roche Ltd.; Amgen; Kirin Brewery Co. Ltd. Chemotherapy-induced neutropenia (2/91); bone marrow transplant (6/94); severe chronic neutropenia (12/94); support peripheral blood progenitor cell transplantation (12/95); acute myelogenous leukemia (4/98) Amgen Inc. Sensipar and NPS Pharmaceuticals Inc. Amgen Inc. To treat secondary hyperparathyroidism in kidney disease patients on dialysis, and to treat elevated calcium levels in patients with parathyroid carcinoma (3/04) Anika Therapeutics Inc. Shellgel Anika Therapeutics Inc. For protecting eye tissue and maintaining eye shape during ophthalmic surgery (7/01) Orthovisc Ortho Biotech Products LP Pain from osteoarthritis of the knee (2/04) AnorMED Inc. Fosrenol Shire Pharmaceuticals Group plc To reduce elevated blood levels of phosphate in patients with end-stage renal disease (10/04) Athena Neurosciences Inc. (subsidiary of Elan Corp plc) Zanaflex Athena Neurosciences Inc. Spasticity associated with spinal cord injuries and multiple sclerosis (12/96) Atrix Laboratories Inc. Atrisorb Barrier Block Drug Co. Periodontal disease (3/96); periodontal surgery (9/00) Eligard Sanofi-Synthelabo Inc. 7.5 mg for advanced prostate cancer (1/02); 22.5 mg for advanced prostate cancer (7/02); 30 mg for advanced prostate cancer (2/03) Avanir Pharmaceuticals Inc. Abreva (Docosanol) GlaxoSmithKline plc Cold sores and fever blisters (7/00) Aventis Behring LLC Helixate Aventis Behring LLC and Bayer Biological Products Business Unit Helixate was approved for treatment of hemophilia A (2/94); second-generation factor VIII approved for treatment of hemophilia A (6/00) BioChem Pharma Inc. (merged with Shire Pharmaceuticals Group) 3TC (Epivir) GlaxoSmithKline plc In combination with AZT for HIV infection and AIDS (1 1/95) Combivir GlaxoSmithKline plc Single-tablet formulation of 3TC and AZT for HIV (9/97) Pacis BCG BioChem Pharma Bladder cancer (3/00) Trizivir ND HIV (1 1/00) 368 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) Biogen Idec Inc. and Elan Corp. plc Tysabri Biogen Idec Inc. and Elan Corp. plc For treating relapsing forms of multiple sclerosis (1 1/04) Biogen Idec Inc. Amevive Biogen Idec Inc. Approved for treating chronic plaque psoriasis (1/100 Avonex Biogen Inc. Multiple sclerosis (5/96); new labeling allows use after first MS attack (2/03) Energix-B GlaxoSmithKline plc Hepatitis B vaccine (9/89) Intron-A Schering-Plough Corp. Hairy-cell leukemia (6/86); genital warts (6/88); AIDS-related Kaposi’s sarcoma (1 1/88); hepatitis C (2/91); hepatitis B (7/92); adjuvant with surgery in those with high risk of malignant melanoma recurrence (12/95); low-grade non-Hodgkin’s lymphoma (1 1/97); hepatitis B in pediatric patients (8/98) Recombivax HB Merck & Co. Inc. Hepatitis B vaccine (7/86) Biomatrix Inc. Synvisc Wyeth Pharmaceuticals Viscosuplementation treatment for arthritis of the knee (8/97) Biosonix Ltd. FlowGuard Neoprobe Corp. Diagnostic product to determine blood flow in noninvasive diagnostic and intraoperative applications (2/02) Biota Holdings Ltd. Relenza Glaxo Wellcome plc Zanamivir for inhalation for treatment of influenza A and B (7/99) Bio-Technology General Corp. BioTropin Cannot sell in U.S. Human growth hormone deficiency in children due to court injunction (5/95) BioTime Inc. Hextend N/A Boehringer Mannheim Corp. Retavase Centocor Inc. (acquired Thrombolytic agent for acute myocardial infarction marketing rights from (10/96) Boehringer Mannheim Corp. and Dupont Merck Pharmaceuticals Corp. in 1998) Hypovolemia (3/99) Cambridge Humria Antibody Technology Group plc Abbott Laboratories Rheumatoid arthritis (12/02); expanded label to include reducing symptoms and inhibiting structural damage (1/03); improvement in physical function in RA patients (8/04) Celgene Corp. Novartis Pharmaceuticals Corp. Attention deficit/hyperactivity disorder (1 1/01) Focalin BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 369 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) CellPro Inc. Ceprate SC System CellPro Inc. Separated cells returned to patient after chemotherapy or marrow-destroying procedures to restore bone marrow (12/96) Celltech Chiroscience Group (unit of Celltech Group plc; acquired by UCB SA) Mylotarg Wyeth Targeted chemotherapy agent to treat patients 60 years and older in first relapse with CD33-positive acute myeloid leukemia who are not considered candidates for cytotoxic chemotherapy (5/00) Celltech Group plc (acquired by UCB SA) Metadate CD Celltech Group plc Attention deficit hyperactivity disorder (4/01) Cell Therapeutics Inc. Trisenox Cell Therapeutics Inc. Acute promyelocytic leukemia (9/00) Centocor Inc. (unit of Johnson & Johnson) Remicade Centocor Inc. Crohn’s disease (8/98); rheumatoid arthritis (1 1/99); for use in conjunction with methotrexate to inhibit the progression of damage in patients with moderately to severely active rheumatoid arthritis (1/01); to be used in combination with methotrexate to improve physical function in patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to methotrexate alone (12/02); for long-term remissionlevel control of symptoms associated with Crohn’s disease (7/02); fistulizing Crohn’s disease (4/03); for use as a first-line treatment in moderate to severe RA (9/04); ankylosing spondylitis (12/04) ReoPro Eli Lilly and Co. To inhibit platelet aggregation in high-risk angioplasty (12/94) Cephalon Inc. Provigil Cephalon Inc. Treatment for excessive daytime sleepiness associated with narcolepsy (12/98); excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome and shift-work sleep disorder (1/04) Chiron Corp. Betaseron Berlex Laboratories Inc. Relapsing, remitting multiple sclerosis (7/93); new labeling approved to include studies in secondary progressive MS, and for reducing exacerbations in relapsing forms of the disease (3/03) Proleukin Chiron Corp. 370 Renal cell carcinoma (5/92); metastatic melanoma (1/98) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) Chiron Corp. and OrthoClinical Diagnostics Inc. (unit of Johnson & Johnson) RIBA HCV 3.0 Strip Immunoblot Assay OrthoClinical Diagnostics Inc. Confirmatory test for hepatitis C (2/99) Chiron TheraAredia peutics (business unit of Chiron Corp.) and Ciba Pharmaceuticals (division of Novartis AG) Chiron Corp. Treatment of metastatic bone disease in patients with breast cancer (used in conjunction with standard therapy) (8/96) Chiron Vision (unit of Chiron Corp.; division since acquired by Bausch & Lomb) Chiron Corp. Cytomegalovirus retinitis infection in AIDS patients (3/96) CollaGenex Periostat Pharmaceuticals Inc. CollaGenex For the treatment of adult periodontitis in a new CollaGenex tablet formulation (2/01) Connetics Corp. Luxiq Connetics Corp. Relief of inflammatory and pruritic manifestations of corticoid-responsive dermatoses of the scalp (3/99) Olux Connetics Corp. Short-term topical treatment of the inflammatory and pruritic manifestations of moderate to severe corticoid-responsive dermatoses of the scalp (5/00); for the short-term topical treatment of mild to moderate plaque-type psoriasis of non-scalp regions excluding the face and intertriginous areas (12/02) Bexxar GlaxoSmihtKline plc For treating non-Hodgkin’s lymphoma (6/03) Corixa Corp. Vitrasert COR Therapeutics Integrilin Inc. (acquired by Millennium Pharmaceuticals Inc.) Schering-Plough Corp./ Acute coronary syndrome and angioplasty (5/98) COR Therapeutics CoTherix Inc. Ventavis CoTherix Inc. For treating pulmonary arterial hypertension in patients with NYHA Class III or IV symptoms (12/04) Cubist Pharmaceuticals Inc. Cubicin Cubist Skin infections caused by Gram-positive bacteria (9/03) Curis Inc. OP-1 Stryker Corp. To repair and regenerate tissue (10/01) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 371 Biotechnology Products On The Market Company* Product Marketer Cypress Bioscience Inc. and Fresenius Hematology Inc. (subsidiary of Fresenius AG) Prosorba Column Cypress Bioscience Inc. Moderate to severe rheumatoid arthritis (3/99) Cytogen Corp. Quadramet Cytogen Corp. Radiopharmaceutical for pain associated with bone cancer (3/97) Debiopharm SA Trelstar LA Debiopharm SA Advanced-stage prostate cancer (7/01) DepoTech Corp. (subsidiary of SkyePharmplc) and Chiron Corp. DepoCyt Chiron Corp. Lymphomatous meningitis (4/99) Eli Lilly and Co. Humalog Eli Lilly and Co. Diabetes (6/96) Humatrope Eli Lilly and Co. Human growth hormone deficiency in children (3/87); somatotropin deficiency syndrome in adults (8/96) Xigris Eli Lilly and Co. Sepsis (1 1/01) Endo Pharmaceuticals Inc. and SkyePharma plc DepoDur Endo Pharmaceuticals Inc. For treating pain following major surgery (5/04) Enzon Inc. Adagen Enzon Inc. Treatment of infants and children with severe combined immunodeficiency (1990) Oncospar Rhone-Poulenc Rorer Inc. Acute lymphoblastic leukemia (2/94) Peg-Intron Schering-Plough Corp. Chronic hepatitis C (1/01) Peg-Intron Powder Schering-Plough Corp. Chronic hepatitis C in patients with compensated liver disease (8/01) Rebetol Schering-Plough Corp. To be used in combination with Intron A injection for chronic hepatitis C (7/01); approved for pediatric hepatitis C (7/03) Eyetech Pharmaceuticals Inc. and Pfizer Inc. For for treating wet age-related macular degeneration (12/04) Eyetech Macugen Pharmaceuticals Inc. (acquired by OSI Pharmaceuticals Inc.) 372 Indication (U.S. Approval Date) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) GelTex Pharmaceuticals Inc. (acquired by Genzyme Corp.) Renagel Genzyme General Reduction of serum phosphorus in patients with end-stage renal disease (1 1/98); reduction of serum phosphorus in hemodialysis patients with end-stage renal disease (7/00) Welchol Sankyo Parke Davis Adjunctive therapy to diet and exercise for the reduction of low-density lipoprotein (LDL) cholesterol in patients with primary hypercholesterolemia (5/00) Actimmune InterMune Pharmaceuticals Inc. Chronic granulomatous disease (12/90); treatment for severe malignant osteopetrosis (2/00) Avastin Genentech Inc. For use in first-line combination treatment in metastatic colorectal cancer (2/04) Activase Genentech Inc. Acute myocardial infarction (1 1/87); acute pulmonary embolism (6/90); acute ischemic stroke (6/96); accelerated infusion (4/95); acute ischemic stroke within three hours of symptom onset (subset of adults whose strokes are caused by bleeding are not included in treatment group) (6/96) Cathflo Activase Genentech Inc. For use in breaking down clots in central venous catheters (9/01) Herceptin Genentech Inc. Metastatic breast cancer in combination with paclitaxel as a first-line agent and as single agent in women who have failed other therapies (9/98) Humulin Eli Lilly and Co. Diabetes (10/82) Kogenate Bayer Corp. Hemophilia A (12/93) Nutropin AQ Genentech Inc. Growth failure associated with chronic renal insufficiency (1 1/93); growth hormone inadequacy (1/94); for treating children whose short stature is caused by growth hormone inadequacy or by chronic renal insufficiency (1/96); expanded label to include treatment of short stature in females with Turner’s syndrome (12/96) Protropin Genentech Inc. Growth hormone inadequacy; growth failure associated with chronic renal insufficiency (10/85) Pulmozyme Genentech Inc. Cystic fibrosis (12/93); treatment of cystic fibrosis in severely ill patients (less than 40% lung function) (12/96); treatment of cystic fibrosis in infants and young children (3/9) Genentech Inc. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 373 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) Genentech Inc. Roferon-A Hoffmann-La Roche Inc. Hairy-cell leukemia (6/86); AIDS-related Kaposi’s sarcoma, Philadelphia chromosome positive chronic myelogenous leukemia (1 1/88) TNKase (tenecteplase) Genentech Inc. Single-bolus thrombolytic for the treatment of acute myocardial infarction; can be administered over five seconds in a single dose (6/00) Genentech Inc. and Tanox Inc. Xolair Genentech and Novartis Pharma AG Approved for treating asthma (6/03) Genentech Inc. and XOMA Ltd. Raptiva Genentech Chronic moderate to severe plaque psoriasis (10/03) GeneSoft Factive Pharmaceuticals Inc. (merger formed Oscient Pharmaceuticals Inc.) Oscient Pharmaceuticals Community-acquired pneumonia and acute bacterial exacerbations of chronic bronchitis (4/03) Genetics Institute Inc. (subsidiary of American Home Products Corp.) Neumega Genetics Institute Inc. Blood platelet booster (1 1/98) Recombinate Baxter International Inc. Blood clotting Factor VIII for hemophilia A (12/92) ReFacto Genetics Institute of Wyeth-Ayerst FDA approved ReFacto for control and prevention of bleeding and surgical prophylaxis with hemophilia A patients (3/00) Procleix HIV-1/ Chiron Corp. Test to be used to detect human immunodeficiency Gen-Probe Inc. virus HCV Assay and the Procleix Semi-Automated System Type 1 and hepatitis C virus (2/02) Gensia Laboratories Ltd. (subsidiary of Gensia Inc.) Etoposide Injection Gensia Laboratories Ltd. Treatment of small-cell lung cancer and refractory testicular tumors (7/96) Genta Inc. Ganite Genta Inc. Cancer-related hypercalcemia (9/03) Genzyme Corp. Aldurazyme and BioMarin Pharmaceutical Inc. Clolar Fabrazyme 374 Genzyme and BioMarin Mucopolysaccharidosis-1 (4/03) Genzyme Corp. For treating children with refractory or relapsed acute lymphoblastic leukemia (12/04) Genzyme Corp. Fabry’s disease (4/03) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) Genzyme Corp. Autologous cultured chondrocytes to repair knee cartilage damage (8/97) Genzyme Corp. Type I Gaucher’s disease (4/91) Cerezyme Genzyme Corp. Type I Gaucher’s disease (5/94) Seprafilm Genzyme Corp. To reduce postsurgical adhesions following open abdominal or pelvic surgery (8/96) Thyrogen Knoll Pharmaceutical Co. Follow-up diagnostic for patients who have been treated for thyroid cancer (12/98) Truvada Gilead Sciences Inc. The Emtriva-Viread combination product was approved for use in HIV regimens (8/04) Emtriva Gilead Sciences Approved for treating HIV (7/03) AmBisome Fujisawa Healthcare Inc. Label expansion for injectable liposomal formulation of aphotericin B for treatment of cryptococcal meningitis in HIV-infected patients (7/00) Hepsera Gilead Sciences Inc. Chronic hepatitis B (9/02) Tamiflu Hoffmann-La Roche Inc. Influenza A and B (10/99); flu prevention (1 1/00); influenza for children ages 1 to 12 (12/00) Viread Gilead Sciences Inc. HIV (10/01) Vistide Pfizer Inc. To delay progression of cytomegalovirus retinitis in AIDS patients (6/96) Guilford Pharmaceuticals Inc. (merged with MGI Pharma Inc.) Gliadel Rhone-Poulenc Rorer Inc. For use as adjunct to surgery to prolong survival of patients with recurrent glioblastoma multiforme (second-line therapy) (9/96); first-line therapy in high-grade malignant glioma (2/03) IDEC Pharmaceuticals Corp. (merged with Biogen Inc.) and Genentech Inc. Rituxan IDEC Pharmaceuticals Corp. and Genentech Inc. Monoclonal antibody for low-grade non-Hodgkin’s lymphoma recurrences (1 1/97); for retreatment after a prior course of Rituxan therapy, doubling of infusions and treatment of bulky disease, or tumors greater than 10 centimeters, for patients with relapsed or refractory, low-grade or follicular, CD20-positive B-cell non-Hodgkin’s lymphoma (5/01) IDEC Pharmaceuticals Corp. (merged with Biogen Inc.) Zevalin IDEC Pharmaceuticals Corp. Non-Hodgkin’s lymphoma (2/02) Genzyme Corp. Carticel and BioMarin Pharmaceutical Inc. Ceredase Gilead Sciences Inc. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 375 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) IGEN Inc. — — Test for detection and quantitation of residual DNA in biopharmaceutical products ILEX Oncology Inc. Campath and Millennium Pharmaceuticals Inc. Berlex Laboratories Inc. Leukemia (5/01) ImClone Systems Inc. Erbitux Bristol-Myers Squibb Co. For patients with metastatic colorectal cancer who are refractory to or intolerant of irinotecan (2/04) Immunex Corp. (acquired by Amgen Inc.) Enbrel Wyeth and Amgen Inc. Rheumatoid arthritis (10/98); severely active polyarticular-course juvenile rheumatoid arthritis (5/99); early stage rheumatoid arthritis (6/00); psoriatic arthritis (1/02); improving physical function in patients with moderately to severely active RA (8/03); expanded label in psoriatic arthritis (8/03) ankylosing spondylitis (10/03); chronic, moderate to severe plaque psoriasis (4/04); to induce a major clinical response in RA patients (9/04) Etoposide Injection SuperGen Inc. Treatment of refractory testicular tumors and smallcell lung cancer (3/96) Leukine Immunex Corp. Neutropenia resulting from chemotherapy in acute myelogenous leukemia (9/95); bone marrow transplant engraftment or failure (1 1/95); peripheral blood stem cell mobilization (12/95); to stimulate production of white blood cells in patients undergoing bone marrow and peripheral blood progenitor cell transplants and for treating chemotherapyinduced neutropenia (1 1/96) Novantrone Immunex Corp. Treatment of hormone-refractory prostate cancer (in combination with steroids) (1 1/96); secondary progressive relapsing-remitting multiple sclerosis (10/00) Immunomedics Inc. CEA-Scan Mallinckrodt Inc. In vivo diagnostic imaging agent to determine site and extent of colorectal cancer (for use in conjunction with standard diagnostic tests) (7/96) Indevus Pharmaceuticals Inc. Sanctura Indevus Pharmaceuticals For treating overactive bladder (5/04) Inc. and Pliva d.d. InKine Visicol Pharmaceutical Co. Inc. (acquired by Salix Pharmaceuticals Inc.) 376 InKine Pharmaceuticals Bowel cleansing for colonoscopy (9/00); new, smaller Visicol tablet formulation that contains less microcrystalline cellulose for bowel cleansing prior to colonoscopy (3/02) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products On The Market Company* Product Marketer Inspire Pharmaceuticals Inc. Elistat Inspire Pharmaceuticals Persistent itching associated with allergic conjuctivitis (10/03) Integra LifeSciences Corp. Artificial Skin Dermal Regeneration Template Integra LifeSciences Corp. Treatment of full-thickness or deep partialthickness burns where conventional autograft is not available or desirable (to regenerate body’s own dermis) (3/96) DuraGen DuralGraft Matrix Integra LifeSciences Corp. Dural closure in neurological procedures (7/99) Interferon Sciences Inc. Alferon N Injection The Purdue Frederick Co. Genital warts (10/89) Isis Pharmaceuticals Inc. Vitravene CIBA Vision Corp. Treatment of cytomegalovirus retinitis in AIDS patients (8/98) ISTA Pharmaceuticals Inc. Istalol ISTA Pharmaceuticals Inc. For treating glaucoma (6/04) Vitrase ISTA Pharmaceuticals Inc. For use as a spreading agent to facilitate the dispersion and absorption of other drugs (5/04) Ontak Ligand Persistent or recurrent cutaneous T-cell lymphoma whose cells express the CD25 component of the IL-2 receptor (2/99) Panretin Gel Integrated Commercialization Solutions Dermal lesions in AIDS-related Kaposi’s sarcoma (2/99) Simulect Novartis AG Acute rejection episodes in renal transplants (5/98) Targretin Ligand Refractory cutaneous T-cell lymphoma (12/99); cutaneous lesions in patients with early stage cutaneous T-cell lymphoma who have refractory or persistent disease after other therapies or who have not tolerated other therapies (6/00) ICOS Corp. and Eli Lilly and Co. Cialis ICOS and Lilly Erectile dysfunction (1 1/03) MedImmune Inc. CytoGam Connaught Laboratories Inc. Prevention of cytomegalovirus in kidney transplant patients (1 1/91); prophylaxis against CMV disease associated with kidney, lung, liver, pancreas and heart transplants (12/98) Ligand Pharmaceuticals Inc. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Indication (U.S. Approval Date) 377 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) MedImmune Inc. RespiGam American Home Products Corp. (NYSE:AHP) Prevention of respiratory syncytial virus in children under 24 months of age with bronchopulmonary dysplasia or a history of premature birth (1/96) Synagis MedImmune Inc. and Abbott Laboratories Prevention of respiratory syncytial virus in children and infants (6/98); new labeling for use in children with congenital heart disease (9/03); new liquid formulation approved (7/04) FluMist MedImmune Inc. Vaccine approved for influenza (6/03) MGI Pharma Inc. and Helsinn Healthcare SA Aloxi MGI Pharma Nausea and vomiting associated with chemotherapy (7/03) Millennium Pharmaceuticals Inc. Velcade Millennium Pharmaceuticals Multiple myeloma (5/03) Nabi Nabi-HB Biopharmaceuticals and Cangene Corp. N/A Hepatitis B (3/99) NaPro BiotheraPaclitaxel peutics Inc., Abbott injection Laboratories and Bristol-Myers Squibb Co. NaPro Biotherapeutics Inc. and Abbott Laboratories For metastatic cancer of the ovary after the failure of first-line or subsequent chemotherapy and for metastatic breast cancer after the failure of combination chemotherapy for metastatic disease (5/02) Nektar Therapeutics Inc. Somavert Pharmacia Corp. For treating acromegaly (3/03) NeoRx Corp. Verluma Dupont Merck Pharmaceuticals Inc. (Joint venture of E.I. Dupont & Co. and Merck & Co. Inc.) In vivo diagnostic imaging agent used to determine extent of disease in patients diagnosed with smallcell lung cancer (8/96) Neurobiological Technologies Inc. Namenda Forest Laboratories Inc. Moderate to severe Alzheimer’s disease (10/03) Nexell Therapeutics Inc. Isolex 300/ Isolex 300i Nexell Therapeutics Inc. Ex vivo stem cell selection for patients undergoing high-dose chemotherapy and bone marrow transplants (7/99) NeXstar Pharmaceuticals Inc. (acquired by Gilead Sciences Inc.) DaunoXome Swedish Orphan AB First-line therapy for Kaposi’s sarcoma in AIDS patients (4/96) 378 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) North American Vaccine Certiva Abbott Laboratories Inc. Combined diphtheria, tetanus and acellular pertussis vaccine (8/98) Novo Nordisk A/S Norditropin Novo Nordisk A/S Human growth hormone deficiency in children (5/95); recombinant somatropin (human growth hormone) for long-term treatment of children who have growth failure due to inadequate secretion of endogenous growth hormone (6/00) Novolin Novo Nordisk A/S Insulin-dependent diabetes mellitus (7/91) NovoSeven Novo Nordisk A/S Bleeding episodes in hemophiliacs (3/99) Nycomed Amersham plc EchoSeed Nycomed Amersham plc Prostate cancer (6/01) Octapharma AG Octagam Octapharma AG For treating primary immunodeficiency diseases (5/04) OraPharma Inc. Arestin OraPharma Inc. Adjunct treatment for periodontitis following scaling and root planing (2/01) Organogenesis Inc. Apligraf Novartis AG Venous leg ulcers (5/98); living, bi-layered skin substitute for use in the treatment of diabetic foot ulcers (6/00) Orphan Medical Inc. Xyrem Orphan Medical Inc. For cataplexy associated with narcolepsy (7/02) Ortec International Composite Inc. cultured skin (OrCel) Ortec International Inc. For use in patients with recessive dystrophic epidermolysis bullosa undergoing hand reconstruction surgery; also for covering donor sites (2/01); for healing donor site wounds in burn victims (9/01) Ortho Biotech Inc. (unit of Johnson & Johnson) Orthoclone OKT3 Ortho Biotech Inc. Reversal of acute kidney rejection (6/86); reversal of heart and liver transplant rejection (6/93) OSI Pharmaceuticals Inc. and Genentech Inc. Tarceva Genentech Inc. For treating advanced or metastatic non-small-cell lung cancer in those who have failed at least one chemotherapy regimen (1 1/04) Pharmacia Corp. (unit of Pfizer Inc.) Genotropin Pharmacia & Upjohn Growth hormone deficiency in children (8/95) Fragmin Pharmacia & Upjohn Prevention of deep-vein thrombosis following hip replacement surgery (3/99); unstable angina and non-Q-wave myocardial infarction (5/99) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 379 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) Pharmion Corp. Vidaza Pharmion Corp. For treating all five subtypes of myelodysplastic syndrome (5/04) PhotoCure ASA Metvix PDT PhotoCure ASA For premalignant skin changes or actinic keratosis (9/02) Praecis Pharmaceuticals Inc. Plenaxis Praecis Pharmaceutials Palliative treatment of prostate cancer (1 1/03) ProCyte Corp. Iamin Gel Kissei Pharmaceutical Co. Wound dressing and management (2/96) OsmoCyte ProCyte Corp. Ultra Pillow Wound Dressing Dressing for a variety of exudating chronic and acute wounds (both infected and noninfected) (12/96) CroFab Protherics plc FDA approved CroFab, an antivenom to treat rattlesnake bites (12/00) DigiFab Protherics plc Digoxin toxicity (9/01) Photofrin Sanofi Winthrop Inc. Advanced throat cancer (12/95) Visudyne CIBA Vision Corp./ Novartis Ophthalmics Wet age-related macular degeneration (4/00); the form of class subfoveal choroidal neovascularization that occurs in people 30 and older (8/01) Repligen Corp. SecreFlo Repligen Corp. To stimulate pancreatic secretions to aid in the diagnosis of pancreatic exocrine dysfunction, or chronic pancreatitis, and stimulation of gastrin secretion to aid in the diagnosis of gastrinoma (4/02); to aid in the location and cannulation of the pancreatic ducts in patients undergoing ERCP (1 1/02) Santarus Inc. Zegerid Santarus Inc. For treating gastrointestinal bleeding in critically ill patients and for short-term treatment of active benign gastric ulcers (12/04) Rapinex Santarus Inc. For treating heartburn and related symptoms (6/04) Scios Inc. (acquired by Johnson & Johnson) Natrecor Scios Inc. Acute congestive heart failure (8/01) Sepracor Inc. Lunesta Sepracor Inc. For treating insomnia (12/04) Protherics plc QLT Phototherapeutics Inc. 380 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) Sepracor Inc. Xopenex Sepracor Inc. Treatment and prevention of bronchospasm (3/99); for treatment or prevention of bronchospasm in children ages 6 to 1 1 years old with reversible obstructive airway disease, such as asthma (1/02) Sequus Pharmaceuticals Inc. (acquired by Alza Corp.) Amphotec (aka Amphocil) Sequus Pharmaceuticals Inc. Invasive aspergillosis infections (2nd-line therapy) (1 1/96) Doxil Sequus Pharmaceuticals Inc. Refractory AIDS-related Kaposi’s sarcoma (1 1/95) Luveris Serono SA For use with Gonal-f to stimulate follicular development in infertile hypogonadotropic hypogonadal women (10/04) Fertinex Serono Laboratories Inc. Infertility treatment (8/96); hormone deficiency (10/96) Gonal-F Serono SA Recombinant follicle-stimulating hormone for treatment of infertility in men and women (6/00); multi-dose for infertility (3/01) Ovidrel Serono SA Infertility due to anovulation and promote final egg maturation in ovaries of women undergoing assisted reproductive technologies (10/00) Rebif Serono SA For relapsing forms of multiple sclerosis (3/02) Saizen Serono Laboratories Inc. Growth hormone deficiency in children (10/96); adult growth hormone deficiency (8/04) Serostim Serono SA FDA granted full approval for treating AIDS wasting (10/03); approved for short bowel syndrome (12/03) SkyePharma plc Solaraze SkyePharma plc Actinic keratosis (10/00) SuperGen Inc. Daunorubicin SuperGen Inc. Acute leukemia (1 1/01) Mitozytrex SuperGen Inc. For disseminated adenocarcinoma of the stomach or pancreas in proven combination with other approved chemotherapuetic agents (1 1/02) Copaxone Teva Pharmaceutical Industries Ltd. To reduce flare-ups in relapsing multiple sclerosis (12/96) Serono SA Teva Pharmaceutical Industries Ltd. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 381 Biotechnology Products On The Market Company* Product Marketer Indication (U.S. Approval Date) Texas Biotechnology Corp. Argatroban (formerly Novastan) GlaxoSmithKline plc Anticoagulant for prevention of treatment of thrombosis associated with heparin-induced thrombocytopenia (6/00); patients with heparininduced thrombocytopenia undergoing percutaneous coronary interventions (4/02) The Liposome Co. Inc. (acquired by Elan Corp plc) Abelcet The Liposome Co. Aspergillosis in those unable to take conventional drug (1 1/95); treatment of all types of confirmed or suspected invasive fungal infections (especially candidiasis) as 2nd-line therapy (10/96); severe systemic fungal infections (9/99) The Medicines Co. Angiomax Innovex Inc. Unstable angina (12/00) Trimeris Inc. Fuzeon Trimeris and Hoffmann-La Roche Inc. For use in combination HIV regimens (3/03) United Remodulin Therapeutics Corp. United Therapeutics Corp. Pulmonary arterial hypertension (5/02) U.S. Bioscience Inc. (acquired by MedImmune Inc.) Alza Corp.; Southern Research Institute To reduce kidney toxicity after chemotherapy for advanced ovarian cancer (12/95); to reduce the cumulative kidney toxicity of cisplatin in patients undergoing chemotherapy for non-small-cell lung cancer (3/96); moderate-to-severe post-operative, radiation-induced xerostomia in patients undergoing radiation treatment for head and neck cancer (6/99) Vernalis Group plc Frovatriptan Elan Corp. plc For the acute treatment of migraine (1 1/01) Vertex Pharmaceuticals Inc. Lexiva Vertex and GlaxoSmithKline plc For treating HIV infection in adults in combinanaton with other antiretroviral drugs (10/03) Vertex Pharmaceuticals Inc. Agenerase GlaxoSmithKline plc HIV infection in children ages 4 and older and in twice-daily dosage with other antiretrovirals for HIV infection (4/99) Vysis Inc. UroVysion Vysis Inc. Monitoring recurrence of bladder cancer (8/01) Wyeth-Ayerst Laboratories Rapamune Wyeth-Ayerst Laboratories Prevention of organ rejection following renal transplantation (9/99) 382 Ethyol BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Biotechnology Products On The Market Notes: This chart is a broad overview of biotech and biotech-related products on the market in the U.S. and covers products approved through 2004. Products on the market that were approved in 2005 are listed in the previous chart. Not all of the companies represented are biotechnology firms. Large pharmaceutical companies are included when the products they developed represented breakthroughs in the area and/or where biotech companies were developing competing products. *Unless otherwise noted, companies were the original firms that obtained approval. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 383 FDA Actions On Pending Applications In 2005 Company* (Symbol) Product Description Indication Action/Date Adolor Corp. (ADLR) and GlaxoSmithKline plc (UK) Entereg Alvimopan capsules; mu opioid antagonist Post-operative ileus The FDA issued an approvable letter saying additional proof of efficacy was needed to support the NDA filed in June 2004 (7/22) Alkermes Inc. (ALKS) and Cephalon Inc. (CEPH) Vivitrol (formerly Vivitrex) Long-acting, injectable form of naltrexone Alcohol dependence The FDA issued an approvable letter, which calls only for labeling discussions and delivery of certain preclinical pharmacokinetic data (12/28) Alkermes Inc. (ALKS) and Johnson & Johnson Risperdal Risperidone formulated Consta in Alkermes’ long-acting (FDA-approved) Medisorb technology Psychosis of Alzheimer’s disease The FDA issued J&J a not-approvable letter on the supplemental NDA filing (5/26) Avanir Pharmaceuticals Inc. (AMEX:AVN) Neurodex Pseudobulbar affect Action on the NDA filed in June will be delayed following the FDA’s request for additional information (9/22) Celgene Corp. (CELG) Thalomid Thalidomide (FDA-approved) Multiple myeloma The FDA issued an approvable letter on the supplemental NDA, requesting revised labeling and updated safety and some additional patient information (1 1/15) Cephalon Inc. (CEPH) Actiq Oral transmucosal (FDA-approved) fentanyl citrate; sugarfree formulation Pain in cancer patients The FDA approved the sugar-free formulation of the alreadyapproved drug (9/12) Cephalon Inc. (CEPH) Sparlon Attention deficit/ hyperactivity disorder Received an approvable letter from the FDA on supplemental NDA filed in December 2004 (10/21) Chiron Corp. (CHIR) Fluvirin Influenza vaccine (FDA-approved) Influenza The FDA OK’d Chiron’s manufacturing facility in the UK, allowing the company to provide the vaccine for the 2005-06 flu season (8/31) Chiron Corp. (CHIR) Pulminiq For use in patients getting lung transplants The FDA said the product was approvable but that an additional trial was needed to confirm efficacy (7/15) 384 Oral combination of dextromethorphan and the enzyme inhibitor quinidine New formulation and dosage of modafinil, the active ingredient in the approved product Provigil Cyclosporine inhalation solution BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 FDA Actions On Pending Applications In 2005 Company* (Symbol) Product Critical Therapeutics Inc. (CRTX) Description Indication Action/Date Zyflo Zileuton tablets; (FDA-approved) 5-lipoxygenase inhibitor Asthma The FDA approved supplemental NDA covering new manufacturing process (9/28) Discovery Laboratories Inc. (DSCO) Surfaxin Respiratory distress syndrome in premature infants The FDA said Discovery needed to provide more information in its response letter to the approvable letter received in February (8/15); the questions center on chemistry and manufacturing (8/19) Enzon Pharmaceuticals Inc. (ENZN) Oncaspar PEG-enhanced version of (FDA-approved) the naturally occurring enzyme L-asparaginase Acute lymphoblastic leukemia The FDA approved a labeling change for the pediatric drug, allowing for administration via the intravenous route; it had been approved for intramuscular injection (1 1/10) Inex Pharmaceuticals Corp. (Canada; TSE:IEX) and Enzon Pharmaceuticals Inc. (ENZN) Marqibo (Onco TCS) Vincristine encapsulated in Inex’s TCS (liposomal) drug delivery technology Non-Hodgkin’s lymphoma The FDA said the product was not approvable; the move followed an FDA panel’s recommendation against approval in December (1/19) Inspire Pharmaceuticals Inc. (ISPH) Diquafosol tetrasodium Ophthalmic solution; P2Y2 receptor agonist Dry-eye disease The FDA issued a second approvable letter, saying trials failed to demonstrate efficacy (12/2) La Jolla Pharmaceutical Co. (LJPC) Riquent Abetimus sodium; B-cell toleragen; designed to reduce levels of antibodies to double-stranded DNA Lupus The FDA, which had issued an approvable letter in October 2004 calling for more trials, said the drug was unlikely to gain accelerated approval (3/14) Maxim Pharmaceuticals Inc. (MAXM) Ceplene Histamine dihydrochloride in combination with interleukin-2 Acute myeloid leukemia FDA said another Phase III trial would be necessary before Maxim could apply for regulatory approval (1/18) MGI Pharma Inc. (MOGN) and SuperGen Inc. (SUPG) Dacogen Decitabine for injection; a hypomethylating agent Myelodysplastic syndromes FDA issued approvable letter that calls for review of transfusion requirements from Phase III trial, labeling discussions and certain data submission (9/1) Engineered version of natural human lung surfactant BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 385 FDA Actions On Pending Applications In 2005 Company* (Symbol) Product Description Indication Action/Date Nektar Therapeutics Inc. (NKTR) Exubera Dry-powder, inhaled insulin formulation that uses Nektar technology Type I and II diabetes The FDA told partners SanofiAventis SA and Pfizer Inc. that it is extending the NDA review date to review additional chemistry data (10/30) Neurobiological Technologies Inc. (NTII) Namenda Memantine; NMDA (FDA-approved) receptor antagonist Alzheimer’s disease The FDA issued partner Forest Laboratories Inc. a non-approvable letter on supplemental NDA to expand the label to include treatment of mild AD (7/25) Noven Pharmaceuticals Inc. (NOVN) — Generic fentanyl transdermal system Pain The FDA stopped its review on abbreviated NDA, saying it would not approve the product (9/28) Penwest Pharmaceuticals Co. (PPCO) PW2101 Low-dose formulation of a beta blocker Hypertension and angina The FDA issued a non-approvable letter on the NDA, partly due to kinetic variability and beta blockade as a surrogate for efficacy was not demonstrated; Penwest is dropping the compound (6/29) SuperGen Inc. (SUPG) Orathecin Rubitecan; topoisomeraseI inhibitor in capsule formulation Pancreatic cancer SuperGen withdrew NDA filing after learning package would not be sufficient to gain approval (1/3) Vicuron Pharmaceuticals Inc. (MICU) Dalbavancin Glycopeptide agent from the same class as vancomycin Complicated skin and soft-tissue infections The FDA said it would extend its review date on the NDA for three months; action now was expected by Sept. 21, 2005 (5/1 1) Notes: BLA = Biologics license application; FDA = Food and Drug Administration; IND = Investigational new drug application; NDA = New drug application. Unless otherwise noted, the stock symbols listed for public companies are on the Nasdaq market. TSE = Toronto Stock Exchange. 386 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Licensing Applications Filed And Pending At FDA In 2005 Company* (Symbol) Product Description Indication Action/Date Avanir Pharmaceuticals Inc. (AMEX:AVN) Neurodex Oral combination of dextromethorphan and the enzyme inhibitor quinidine Pseudobulbar affect The company submitted the final modules of its rolling NDA filing (6/30) Barrier Therapeutics Inc. (BTRX) Sebazole Topical formulation of 2% ketoconazole, an antifungal agent Seborrheic dermatitis The FDA accepted for filing the NDA submission; the NDA was submitted in September (12/9) BioDelivery Sciences International Inc. (BDSI) Emezine Formulation of the approved agent prochlorperazine Nausea and vomiting The FDA accepted for review the NDA, which was filed in April (7/20) Biogen Idec Inc. (BIIB) and Elan Corp. plc (Ireland) Tysabri Natalizumab; humanized monoclonal antibody that inhibits adhesion molecules on immune cells Multiple sclerosis They filed a supplemental BLA with the FDA; the product was taken off the market in February due to safety concerns (9/26); the FDA accepted the sNDA and designated it for priority review; the sNDA for market re-entry was filed in September (1 1/17) BioMarin Pharmaceutical Inc. (BMRN) Orapred ODT Prednisolone sodium phosphate tablets; new formulation of Orapred Inflammation reduction The FDA accepted for filing the NDA for Orapred; the NDA was filed in August; the PDUFA date is June 1, 2006 (10/19) Centocor Inc. (unit of Johnson & Johnson) Remicade Infliximab; monoclonal (FDA-approved) antibody that targets tumor necrosis factor-alpha Plaque psoriasis FDA accepted supplemental BLA filing, which seeks approval for treating moderate to severe plaque psoriasis (1 1/7) Cephalon Inc. (CEPH) OraVescent Fentanyl Fentanyl formulated with transmucosal delivery technology Breakthrough cancer pain Filed NDA with FDA seeking approval for managing pain in patients already receiving opioid therapy (9/6) Cephalon Inc. (CEPH) Nuvigil Armodafinil; single isomer of the active ingredient in Provigil (modafinil) Excessive sleepiness Filed NDA with FDA seeking approval for improving wakefulness associated with narcolepsy, shiftwork sleep disorder and obstructive sleep apnea/hypopnea syndrome (3/31) CollaGenex Pharmaceuticals Inc. (CGPI) Oracea Non-antimicrobial tetracycline derivative Rosacea The FDA accepted for review the NDA, which was filed in August (10/3) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 387 Licensing Applications Filed And Pending At FDA In 2005 Company* (Symbol) Product Cubist Pharmaceuticals Inc. (CBST) Indication Action/Date Cubicin Daptomycin for injection; (FDA-approved) a bactericidal antibiotic Bacteremia The FDA accepted and granted priority-review status to sNDA seeking approval to treat bacteremia with known or suspected endocarditis caused by Staphylococcus aureus; the supplemental application was filed in September (1 1/21) CV Therapeutics Inc. (CVTX) Ranexa (ranolazine) Partial inhibitor of fattyacid oxidation Chronic angina Submitted amendment to the NDA, based on results of ERICA trial; an approvable letter was issued in October 2003 (7/27) Discovery Laboratories Inc. (DSCO) Surfaxin Engineered version of natural human lung surfactant Respiratory distress syndrome in premature infants The FDA accepted resubmission by Discovery as a complete response to the approvable letter; completion of the NDA review is expected by April 2006 (10/21) Encysive Pharmaceuticals Inc. (ENCY) Thelin Sitaxsentan; small molecule designed to block endothelin Pulmonary arterial hypertension The FDA accepted the NDA filing and designated it for standard review; the NDA was filed in May (7/14) Enzon Pharmaceuticals Inc. (ENZN) Oncaspar PEG-enhanced version of (FDA-approved) the naturally occurring enzyme L- asparaginase Acute lymphoblastic leukemia The FDA accepted the supplemental BLA filing, which seeks approval of use of the pediatric product in first-line treatment (12/1) Genentech Inc. (NYSE:DNA) Lucentis Genentech Inc. (NYSE:DNA) and Biogen Idec Inc. (BIIB) Rituxan Rituximab; antibody that (FDA-approved) targets and selectively depletes CD20-positive B cells Rheumatoid arthritis The FDA accepted for review the supplemental BLA filed in August and designated it for priority review (10/31) Genentech Inc. (NYSE:DNA) and Biogen Idec Inc. (BIIB) Rituxan Rituximab; antibody that (FDA-approved) targets and selectively depletes CD20-positive B cells Non-Hodgkin’s lymphoma The FDA granted priority review to the BLA filed in August for previously untreated patients with intermediate or aggressive, CD20-positive, B-cell NHL in combination with chemotherapy (10/25) 388 Description Ranibizumab; humanized Wet age-related antibody fragment designed macular to bind and inhibit VEGF-A degeneration Submitted BLA with the FDA, seeking approval for treating neovascular wet AMD (12/30) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Licensing Applications Filed And Pending At FDA In 2005 Company* (Symbol) Product Genentech Inc. (NYSE:DNA) Description Indication Action/Date Avastin Bevacizumab; antibody (FDA-approved) designed to inhibit vascular endothelial growth factor Relapsed, metastatic colorectal cancer Filed supplemental BLA with the FDA seeking approval for use with 5-FU in treating relapsed, metastatic disease (12/19) Genta Inc. (GNTA) Genasense Oblimersen sodium; inhibits function of bcl-2 protein Advanced chronic lymphocytic leukemia Filed NDA with FDA seeking approval of drug with chemotherapy for treating refractory/ relapsed disease (12/29) Genzyme Corp. (GENZ) Myozyme Recombinant human acid alpha-lucosidase enzyme Pompe disease Submitted a BLA to the FDA, seeking approval of the product (7/29) Gilead Sciences Inc. (GILD) Tamiflu Oseltamivir; an oral (FDA-approved) neuraminidase inhibitor Influenza Partner Hoffmann-La Roche Inc. filed a supplemental NDA seeking to extend the prophylaxis indication to include children ages 1 through 12 (4/18) GPC Biotech (Germany; FSE:GPC) Satraplatin Hormonerefractory prostate cancer GPC began rolling NDA submission for drug in combination with prednisone as a second-line chemotherapy treatment (12/15) ImClone Systems Inc. (IMCL) and Bristol-Myers Squibb Co. Erbitux Cetuximab; antibody that (FDA-approved) blocks the epidermal growth factor receptor Head and neck cancer Filed supplemental BLA seeking approval for use with radiation in advanced squamous cell carcinoma of the head and neck and as a monotherapy in platinum-based failures (8/30); the FDA accepted for filing the supplemental BLA designated it for priority review (10/31) InKine Pharmaceutical Co. Inc. (INKP) INKP-102 New-generation sodium phosphate purgative tablet Bowel cleansing prior to colonoscopy The FDA accepted for filing the NDA, which was filed in May (7/26) Insmed Inc. (INSM) SomatoKine Composition of insulinGrowth hormone like growth factor-1 and its insensitivity primary binding protein, BP3 syndrome Company submitted NDA for that indication for which the product has orphan status (1/3) Labopharm Inc. (Canada; TSE:DDS) — Once-daily formulation of the analgesic tramadol Submitted NDA to the FDA seeking approval for the management of moderate to moderately severe pain (1 1/30) Oral platinum compound BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Pain 389 Licensing Applications Filed And Pending At FDA In 2005 Company* (Symbol) Product Description Indication Action/Date MediGene AG (Germany; FSE: MDG) Polyphenon E Ointment Product from green tea leaves designed to block virus binding to cells Genital warts The FDA accepted for filing the NDA on the drug (12/1) MedImmune Inc. (MEDI) CAIV-T Trivalent vaccine; next generation of FluMist; refrigerator-stable formulation Influenza Submitted supplemental BLA seeking approval in preventing influenza in healthy people aged 5 to 49 (9/19) MGI Pharma Inc. (MOGN) and SuperGen Inc. (SUPG) Dacogen Decitabine for injection; a hypomethylating agent Myelodysplastic syndromes The FDA accepted resubmission of data as a complete response to approvable letter issued in September (12/15) Neurochem Inc. (Canada; NRMX) Fibrillex Glycosaminoglycan mimetic with antiamyloid properties Amyloid A amyloidosis Initiated rolling NDA submission with the FDA; complete filing is expected around year-end (8/22) Neurocrine Biosciences Inc. (NBIX) Indiplon Tablet form of a nonInsomnia benzodiazepine agent that targets the GABA-A receptor The company has completed submission of an NDA with the FDA for treating insomnia in both adult and elderly patients (5/26) Neurocrine Biosciences Inc. (NBIX) Indiplon Capsule formulation of a non-benzodiazepine agent that targets the GABA-A receptor Insomnia The FDA accepted for review the NDA for treatment of insomnia in both adult and elderly patients (7/26) NPS Pharmaceuticals Inc. (NPSP) Preos Recombinant human parathyroid hormone Osteoporosis The FDA accepted for review the NDA for treating osteoporosis in postmenopausal women; it was filed in May (7/1 1) Orphan Medical Inc. (ORPH) Xyrem Sodium oxybate oral (FDA-approved) solution Narcolepsy Filed supplemental NDA seeking approval for treating other primary symptoms of narcolepsy, including excessive sleepiness (1/18) Venous ulcers The FDA requested a confirmatory trial to demonstrate safety and effectiveness (4/29) Acute bacterial sinusitis and communityacquired pneumonia Filed supplemental NDA with FDA seeking approval of five-day treatment of the drug for both indications (1 1/21) Ortec OrCel International Inc. (OTC BB:ORTN) Oscient Pharmaceuticals Corp. (OSCI) 390 Collagen sponge seeded with allogeneic epidermal and dermal cells Factive Gemifloxacin mesylate; a (FDA-approved) fluoroquinolone antibiotic BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Licensing Applications Filed And Pending At FDA In 2006 Company* (Symbol) Product Description Indication Action/Date Pozen Inc. (POZN) and GlaxoSmithKline plc (UK) Trexima (MT400) Single-tablet combination of sumatriptan (5-T1B/1D agonist) and naproxen Migraine NDA filed in August was accepted for review by the FDA (10/1 1) Prestwick Pharmaceuticals Inc.* Tetrabenazine Dopamine depletor that works by selectively blocking the VMAT2 transporter Chorea associated with Huntington’s disease Filed NDA with the FDA; the drug is approved in Europe, Canada and Australia and has orphan designation in the U.S. (4/26) Santarus Inc. (SNTS) Zegerid Immediate-release capsule formulation of the proton pump inhibitor omeprazole Gastrointestinal disorders The FDA accepted for filing the NDA submitted in April, which seeks approval for treating heartburn and symptoms of other conditions (6/28) Santarus Inc. (SNTS) Zegerid Tablet formulation of the proton pump inhibitor omeprazole Gastrointestinal disorders The FDA accepted for filing the NDA, which is seeking approval of the chewable tablet formulation for treating heartburn and symptoms of other conditions (7/26) Savient Pharmaceuticals Inc. (SVNT) Soltamox Tamoxifen oral liquid solution Hormonally sensitive breast cancer Filed NDA with the FDA; the drug is a product of Savient subsidiary Rosemont Pharmaceuticals Ltd. (1/6) Sepracor Inc. (SEPR) Arformoterol Long-acting beta-agonist formulated for inhalation; single isomer of formoterol Chronic obstructive pulmonary disease Sepracor filed an NDA with the FDA seeking approval in that indication (12/13) Sucampo Pharmaceuticals Inc.* Lubiprostone Agent that activates specific chloride channels on cells lining the small intestine Chronic idiopathic constipation Filed NDA with the FDA seeking approval to treat CIC and associated symptoms (4/1) Trimeris Inc. (TRMS) and Hoffmann-La Roche Inc. Fuzeon HIV fusion inhibitor; (FDA-approved) enfuvirtide HIV The FDA accepted the filing of a supplemental NDA seeking to include the Biojector 2000 needlefree injection device in the labeling (7/18) Vicuron Pharmaceuticals Inc. (MICU) Anidulafungin Broad-spectrum agent from the echinocandin class Esophageal candidiasis Filed amendment to existing NDA; amendment in invasive candidiasis/candidemia was expected later (5/31) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 391 Licensing Applications Filed And Pending At FDA In 2005 Company* (Symbol) Product Vicuron Pharmaceuticals Inc. (MICU) Vicuron Pharmaceuticals Inc. (MICU) Description Indication Action/Date Anidulafungin Broad-spectrum agent from the echinocandin class Invasive candidiasis/ candidemia Filed NDA with the FDA seeking approval in that indication (8/18) Dalbavancin Complicated skin and softtissue infections NDA for the drug filed in December 2004 was granted priorityreview status by the FDA (2/24) Glycopeptide agent from the same class as vancomycin Notes: Pending applications on which the FDA took some action are included in a separate chart. * Privately held. BLA = Biologics license application; FDA = Food and Drug Administration; IND = Investigational new drug application; NDA = New drug application; PDUFA = Prescription Drug User Fee Act; sNDA = Supplemental new drug application. Unless otherwise noted, the stock symbols listed for public companies are on the Nasdaq market. AMEX = American Stock Exchange; FSE = Frankfurt York Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-the-Counter Bulletin Board; TSE = Toronto Stock Exchange. 392 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Products Not Recommended For Approval By FDA Advisory Panels In 2005 Company* (Symbol) Product Description Indication Action/Date Advanced Magnetics Inc. (AMEX:AVM) and Cytogen Corp. (CYTO) Combidex Molecular imaging agent Cancer diagnosis An FDA advisory panel voted 15-4 against recommending approval for differentiating metastatic from non-metastatic lymph nodes across all cancer types (3/3) Chiron Corp. (CHIR) Pulminiq Cyclosporine inhalation solution For use in patients getting lung transplants An FDA advisory panel split 8-8 on whether the drug provides a survival benefit (6/6) Nektar Therapeutics Inc. (NKTR) Exubera Dry-powder, inhaled insulin formulation that uses technology from Nektar Type I and II diabetes FDA advisory panel recommended approval of the product, from Sanofi-Aventis Group and Pfizer Inc. (9/8) Noven Pharmaceuticals Inc. (NOVN) Daytrana Transdermal patch Attention deficit/ containing methylphenidate hyperactivity disorder FDA advisory committee recommended approval of the drug (12/2) Pozen Inc. (POZN) MT 100 Metoclopramide hydrochloride combined with naproxen sodium FDA advisory panel voted that potential risk for tardive dyskinesia would outweigh benefits; the FDA issued a not-approvable letter in June 2004; Pozen ended development of the drug (8/5) Migraine Notes: Chart does not include recommendations on products that later were acted on by the FDA. Unless otherwise noted, the stock symbols listed for public companies are on the Nasdaq market. AMEX = American Stock Exchange. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 393 Overseas Approvals And Actions In 2005 Company* (Symbol) Product Abbott Laboratories Indication Action/Date Humira Adalimumab; fully human (FDA-approved) antibody designed to block TNF-alpha Ankylosing spondylitis Filed application with European officials seeking approval in that indication (10/4) Abbott Laboratories Humira Adalimumab; fully human (FDA-approved) antibody designed to block TNF-alpha Psoriatic arthritis and rheumatoid arthritis The product was approved in Europe for treating PA and early RA (8/15) Access Pharmaceuticals Inc. (AMEX:AKC) Aphthasol Product containing (FDA-approved) amlexanox Canker sores The product was approved in 10 European Union countries following completion of the Mutual Recognition Procedure (3/3) AEterna Zentaris Inc. (Canada; AEZS) Impavido Oral miltefosine, an alkylphospholipid agent Cutaneous form of leishmaniasis The product was approved in Colombia; the approval also applies to the visceral form of leishmaniasis (3/23) Alfacell Corp. (ACEL) Onconase Ranpirnase; cytotoxic ribonuclease Malignant mesothelioma The product was granted orphan designation in Australia in that indication (3/28) Alkermes Inc. (ALKS) and Johnson & Johnson Risperdal Risperidone formulated Consta in Alkermes’ long-acting (FDA-approved) Medisorb technology Schizophrenia The product was approved in Italy; it has approval in more than 70 countries (9/15) Allos Therapeutics Inc. (ALTH) Revaproxyn (efaproxiral) Brain metastases Withdrew European MAA for use as an adjunct to whole-brain radiation therapy after regulators said data were insufficient (10/1 1) American Pharmaceutical Partners Inc. (APPX) Abraxane Paclitaxel protein-bound (FDA-approved) particles for injection; albumin-bound Metastatic breast cancer The company filed for approval of the product in Canada (6/15) Amgen Inc. (AMGN) Kepivance Palifermin; recombinant (FDA-approved) human keratinocyte growth factor Oral mucositis in cancer patients The product was approved in the European Union in patients undergoing blood and bone marrow transplants (10/28) Amgen Inc. (AMGN) Enbrel Etanercept; anti-tumor (FDA-approved) necrosis factor-alpha antibody Rheumatoid arthritis Wyeth and Takeda Pharmaceutical Co. Ltd. gained approval in Japan for treating those who inadequately responded to other drugs (1/27) 394 Description Small molecule designed to sensitize hypoxic areas of tumors prior to radiation BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Overseas Actions And Approvals In 2005 Company* (Symbol) Product Description Indication Action/Date Antigenics Inc. (AGEN) Oncophage Personalized cancer vaccine based on heatshock protein technology Renal-cell carcinoma The product was granted orphan status in Europe in that indication (6/7) Arexis AB* (Sweden) BSSL Human enzyme-replacement therapy; bile saltstimulated lipase Fat malabsorption in cystic fibrosis patients The European Commission granted orphan status to the drug in that indication (2/9) Ariad Pharmaceuticals Inc. (ARIA) AP23573 Oral form of agent designed to inhibit cellsignaling protein mTOR Soft-tissue and bone sarcomas The EMEA granted orphan designation to the product in Europe in those indications (1 1/15) Ark Therapeutics Group plc (UK; LSE:AKT) Cerepro Adenoviral-mediated gene medicine designed to induce thymidine kinase expression Malignant glioma Filed MAA with European regulators; the application was accepted for review (10/28) Avant Immunotherapeutics Inc. (AVAN) Rotarix Oral, two-dose, live attenuated vaccine developed from a single human strain Rotavirus infection Partner GlaxoSmithKline Biologicals received a positive recommendation from European regulators on marketing application (12/15) AVAX Technologies Inc. (OTC BB: AVXT) M-Vax Autologous, haptenmodified melanoma vaccine Melanoma The product was approved in Switzerland, where it will be sold by Pro Vaccine AG (10/10) BioAlliance Pharma SA* (France) Miconazole Lauriad Oral, bioadhesive buccal tablet containing the antifungal miconazole Oropharyngeal candidiasis Filed an MAA in France, initiating the approval process within the European Union (10/3) BioMarin Pharmaceutical Inc. (BMRN) Naglazyme Galsulfase; an enzyme(FDA-approved) replacement therapy Mucopolysaccharidosis-VI A European advisory panel issued a positive recommendation on the MAA filing (9/15) Caprion Pharmaceuticals Inc.* (Canada) caStx1 and caStx2 Therapeutic monoclonal antibodies Shiga-toxin producing E. coli infections The products were granted orphan drug status in Europe by the EMEA (12/20) Celgene Corp. (CELG) Revlimid Lenalidomide; derivative of Thalomid (thalidomide) Myelodysplastic syndromes The EMEA accepted for review the MAA filing, which was submitted in August (10/26) Centocor Inc. (unit of Johnson & Johnson) Remicade Infliximab; monoclonal (FDA-approved) antibody that targets tumor necrosis factor-alpha Plaque psoriasis The product was approved in Europe for treating moderate to severe plaque psoriasis (10/6) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 395 Overseas Actions And Approvals In 2005 Company* (Symbol) Product Cephalon Inc. (CEPH) Indication Action/Date Vigil Provigil; modafinil (FDA-approved) Shift-work sleep disorder The product was approved in Germany for treating the disorder in in patients working night shifts (8/30) Chiron Corp. (CHIR) Fluvirin Influenza vaccine (FDA-approved) Influenza UK officials lifted the license suspension for Chiron’s Liverpool, UK, manufacturing facility (3/2) Chiron Corp. (CHIR) and Cubist Pharmaceuticals Inc. (CBST) Cubicin Daptomycin for injection; (FDA-approved) a bactericidal antibiotic Complicated skin and soft-tissue infections Scientific committee in Europe issued a positive opinion recommending approval of the marketing application; the MAA was filed in December 2004 (1 1/17) CV Therapeutics Inc. (CVTX) Ranexa (ranolazine) Partial inhibitor of fattyacid oxidation Chronic angina Withdrew MAA filing in Europe after EMEA requested additional pharmacokinetic information; a resubmission is anticipated (10/25) Depomed Inc. (DEPO) and Biovail Corp. (Canada) Glumetza Once-daily, extendedrelease formulation of metformin hydrochloride Type II diabetes The product was approved in Canada; Biovail plans to launch it there in 4Q:05 (6/1) Diurnal Ltd.* (UK) — Modified-release hydrocortisone tablet Congenital adrenal hyperplasia The product was granted orphan designation in Europe in that indication (7/26) Encysive Pharmaceuticals Inc. (ENCY) Thelin Sitaxsentan; small molecule designed to block endothelin Pulmonary arterial hypertension Completed submission of MAA with the EMEA, seeking approval of the product in Europe (7/28); the EMEA accepted for review the MAA (8/17) Eyetech Pharmaceuticals Inc. (EYET) Macugen Pegaptanib sodium (FDA-approved) injection; pegylated anti-VEGF aptamer Wet age-related macular degeneration The product was approved in Canada for treating subfoveal choroidal neovascularization secondary to neovascular AMD (5/5); a European advisory panel recommended approval of the drug (9/16) Genentech Inc. (NYSE:DNA), Tanox Inc. (TNOX) and Novartis AG (Switzerland) Xolair Omalizumab; humanized (FDA-approved) monoclonal antibody to IgE Asthma The European Commission approved the product for treating severe allergic asthma in all 25 EU member states; Novartis AG will market it there (10/27) 396 Description BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Overseas Actions And Approvals In 2005 Company* (Symbol) Product Genentech Inc. (NYSE:DNA) Description Indication Action/Date Avastin Bevacizumab; antibody (FDA-approved) designed to inhibit vascular endothelial growth factor Metastatic colorectal cancer F. Hoffmann-La Roche Ltd. gained approval of the drug in Europe as part of combination regimen (1/14) Generex Biotechnology Corp. (Canada; GNBT) Oral-lyn Oral insulin spray formulation Type I and II diabetes The product was approved in Ecuador; PharmaBrand SA will market the product there (5/3) Genta Inc. (GNTA) Genasense Oblimersen sodium; inhibits function of bcl-2 protein Metastatic melanoma Filed letter of intent seeking approval of the product in Europe for use with dacarbazine (6/30) Genzyme Corp. (GENZ) Thyrogen Thyrotropin alfa for (FDA-approved) injection; a recombinant human thyroid-stimulating hormone Ablation of remnant thyroid tissue The European Commission approved the product for use with radio-iodine (3/3) Gilead Sciences Inc. (GILD) Truvada Fixed-dose combination (FDA-approved) of the company’s approved Viread and Emtriva drugs HIV The European Commission approved the drug in all 25 member states of the European Union for use in combination regimens (2/23) GPC Biotech AG (Germany; GPCB) 1D09C3 Anti-major histocompatibility complex Class II monoclonal antibody Hodgkin’s lymphoma The product was granted orphan designation in Europe in that indication by the EMEA (6/2) GTC Biotherapeutics Inc. (GTCB) ATryn Recombinant human antithrombin Hereditary antithrombin deficiency The EMEA had questions on the MAA, which was filed in February 2004, delaying the expected time to launch (3/16); EMEA extended its timeline for reviewing the MAA until February 2006 (9/16) GW Pharmaceuticals plc (UK; LSE:GWP) Sativex Spray formulation of cannabis extract Spasticity in multiple sclerosis UK regulators denied an appeal to allow marketing of the product without additional trials (6/10) ImClone Systems Inc. (IMCL) Erbitux Cetuximab; antibody that (FDA-approved) blocks the epidermal growth factor receptor Advanced head and neck cancer Partner Merck KGaA got approval of the drug in Switzerland for use with radiation in previously untreated, advanced squamous cell carcinoma of the head and neck (12/22) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 397 Overseas Actions And Approvals In 2005 Company* (Symbol) Product ImClone Systems Inc. (IMCL) and Bristol-Myers Squibb Co. Indication Action/Date Erbitux Cetuximab; antibody that (FDA-approved) blocks the epidermal growth factor receptor Metastatic colorectal cancer The product was approved in Canada for use in combination with irinotecan for treating EGFRexpressing, metastatic, refractory disease (9/15) Inex Pharmaceuticals Corp. (Canada; TSE:IEX) Marqibo (Onco TCS) Non-Hodgkin’s lymphoma Regulatory officials in Canada issued letter of noncompliance, similar to non-approvable letter received earlier from the FDA (1 1/22) InKine Pharmaceutical Co. Inc. (INKP) Visicol Sodium phosphate tablets (FDA-approved) For use as a colonic purgative Partner Zeria Pharmaceutical Co. Ltd. filed for approval in Japan for use as a colonic purgative, bowel cleansing agent or laxative (3/29) Javelin Pharmaceuticals Inc. (OTC BB:JVPH) Dyloject Injectable diclofenac, an analgesic Post-surgical pain UK regulators accepted for review the MAA filing (10/24) Kamada Ltd.* (Israel) — Aerosolized version of its alpha-1 proteinase inhibitor product Congenital emphysema The EMEA granted orphan status to the drug (1/5) Labopharm Inc. (Canada; TSE:DDS) — Once-daily formulation of the analgesic tramadol Pain Authorities approved the drug in France, allowing the company to begin the mutual recognition procedure elsewhere in Europe (1/17); received regulatory approval under the MRP process, paving the way for approval in 22 European countries (9/6) Lorus Therapeutics Inc. (Canada; TSE:LOR) Virulizin Immunotherapy agent designed to stimulate the immune system Pancreatic cancer The product was granted orphan status in Europe in that indication (6/7) Maxim Pharmaceuticals Inc. (MAXM) Ceplene Histamine dihydrochloride in combination with interleukin-2 Acute myeloid leukemia The product was granted orphan designation in Europe in that indication (3/9) MGI Pharma Inc. (MOGN) Aloxi Palonosetron hydrochloride (FDA-approved) injection; a 5-HT3 receptor antagonist Nausea and vomiting in chemotherapy patients Partner Helsinn Healthcare SA gained approval of the product in the European Union (4/4) 398 Description Vincristine encapsulated in Inex’s TCS (liposomal) drug delivery technology BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Overseas Actions And Approvals (Continued) Company* (Symbol) Product Description Indication Action/Date MGI Pharma Inc. (MOGN) and SuperGen Inc. (SUPG) Dacogen Decitabine for injection; a hypomethylating agent Myelodysplastic syndromes Companies withdrew MAA seeking approval in Europe after determining additional clinical data would be required (1 1/15) Millennium Pharmaceuticals Inc. (MLNM) Velcade Bortezomib; proteasome (FDA-approved) inhibitor Multiple myeloma Partner Ortho Biotech gained approval of the drug in Europe for use in second-line treatment (4/28) Myogen Inc. (MYOG) Ambrisentan Type-A selective endothelin receptor antagonist Pulmonary arterial hypertension The product was granted orphan designation in Europe for PAH and chronic thromboembolic pulmonary hypertension (5/2) Nabi Biopharmaceuticals (NABI) Civacir Antibody-based hepatitis C immune globulin Hepatitis C The product was granted orphan status in Europe for preventing recurrent HCV-induced liver disease in liver transplant recipients (6/22) Nabi Biopharmceuticals (NABI) StaphVAX Staphylococcus aureus polysaccharide conjugate vaccine To prevent S. aureus bacteremia The MAA was accepted for review by EMEA; Nabi is seeking approval in Europe to prevent bacteremia in patients with end-stage renal disease on hemodialysis (1/26) Nektar Therapeutics Inc. (NKTR) Exubera Dry-powder, inhaled insulin formulation that uses Nektar technology Type I and II diabetes Sanofi-Aventis SA and Pfizer Inc. received a positive opinion on approval from regulators in Europe (10/13) Neutec Pharma plc (UK; LSE:NTP) Mycograb Agent based on naturally occurring antibody against hsp90 Invasive candidiasis Began marketing application process in Europe for use in combination with amphotericin-B (3/14) NPS Pharmaceuticals Inc. (NPSP) Preotact (Preos) Recombinant human parathyroid hormone Osteoporosis Partner Nycomed Group submitted an MAA in Europe seeking approval for treating postmenopausal osteoporosis (3/1 1) Nuvelo Inc. (NUVO) Alfimeprase Modified fibrolase delivered via catheter; thrombolytic agent Acute peripheral arterial occlusion The EMEA granted orphan designation to the product in Europe (1 1/8) Onyx Pharmaceuticals Inc. (ONXX) and Bayer Pharmaceuticals Corp. Sorafenib RAF kinase and VEGF (BAY 43-9006) inhibitor Advanced kidney cancer They filed an MAA seeking approval of the product in Europe (9/12) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 399 Overseas Actions And Approvals In 2005 Company* (Symbol) Product OSI Pharmaceuticals Inc. (OSIP) and Genentech Inc. (NYSE:DNA) Indication Action/Date Tarceva Erlotinib HCl; small(FDA-approved) molecule HER1/EGFR inhibitor Pancreatic cancer Partner F. Hoffmann-La Roche Ltd. filed for approval of the drug in Europe (1 1/3) OSI Pharmaceuticals Inc. (OSIP) and Genentech Inc. (NYSE:DNA) Tarceva Erlotinib HCl; small(FDA-approved) molecule HER1/EGFR inhibitor Advanced non-small-cell lung cancer The product was approved in Switzerland for treating locally advanced or metastatic disease; F. Hoffmann-La Roche Ltd. has marketing rights in Europe (3/22); product was approved in Canada for treatment following failure of first- or second-line chemotherapy (7/13); partner F. Hoffmann-La Roche Ltd. gained approved of the drug in Europe for use after failure of at least one chemotherapy regimen (9/21) Pharmion Corp. (PHRM) Vidaza Azacitidine for injectable (FDA-approved) suspension; believed to have demethylation and cytotoxic actions Myelodysplastic syndromes Withdrew MAA filing in Europe after learning regulatory authorities will require additional data (1 1/17) Pozen Inc. (POZN) MT 100 Migraine The product was approved in the UK for the acute treatment of migraine; a partner there is being sought (1 1/28) Praecis Pharmaceuticals Inc. (PRCS) Plenaxis Abarelix for injection, (FDA-approved) depot formulation; gonadotropin-releasing hormone antagonist Prostate cancer The drug was approved in Germany to initiate hormonal castration in patients with advanced, hormone-dependent disease, if androgen suppression is appropriate (9/28) Protherics plc (UK; LSE:PTI) Voraxaze Product containing the recombinant enzyme glucarpidase Toxicity from methotrexate The company submitted an MAA seeking approval of the product in Europe (7/28) PTC Therapeutics Inc.* PTC124 Oral agent that targets nonsense mutations Duchenne’s muscular dystrophy and cystic fibrosis The EMEA granted orphan designation to the product in Europe in both indications (7/7) 400 Description Sequential-release tablet containing naproxen and metoclopramide BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Overseas Actions And Approvals In 2005 Company* (Symbol) Product Description Indication Action/Date Revotar Biophar- Bimosiamose maceuticals Inc.* (Germany; majorityowned by Encysive Pharmaceuticals Inc.; ENCY) Topical formulation of pan-selectin antagonist Acute lung injury The product was granted orphan designation in Europe in that indication (6/9) SciGen Ltd. (Singapore; ASX:SIE) SciLin Recombinant human insulin Diabetes The product was approved in Thailand (1 1/14) Serono SA (Switzerland; NYSE:SRA) Raptiva Efalizumab; humanized (FDA-approved) antibody designed to block T cells implicated in psoriasis Plaque psoriasis The product was approved in Canada for treating moderate to severe chronic plaque psoriasis in adult patients (10/31) SGX Pharmaceuticals Inc.* Troxatyl Troxacitabine; nucleoside analogue Acute myelogenous leukemia The product was granted orphan drug status in Europe in that indication (9/27) Shanghai Sunway Biotech Co. Ltd.* (China) H101 Oncolytic adenovirus Nasopharyngeal cancer The product was approved in China for use with chemotherapy (1 1/17) Sinovac Biotech Ltd. (China; AMEX:SVA) Anflu Split-flu type influenza vaccine Influenza Received a GMP certificate in China, the final approval required to sell the product there (10/27) Sinovac Biotech Ltd. (China; AMEX:SVA) Bilive Combined hepatitis A and B vaccine Hepatitis A and B Received final marketing approval in China (1/12) TopoTarget A/S (Denmark; CSE:TOPO) Savene Dexrazoxane; inhibitor of topoisomerase II Antidote to anthracyline extravasation The company filed for approval of the product in Europe (8/18) United Therapeutics Corp. (UTHR) Remodulin Treprostinil sodium (FDA-approved) injection Pulmonary hypertension Approval in 22 additional countries in Europe was gained upon completion of the Mutual Recognition Procedure for treating NYHA Class III primary disease (8/10) United Therapeutics Corp. (UTHR) Remodulin Treprostinil sodium (FDA-approved) injection Pulmonary hypertension French officials issued an approval letter for treating NYHA Class III primary PH, and said the mutual recognition process in the EU would begin in May (3/8) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 401 Overseas Actions And Approvals In 2005 Company* (Symbol) Product Description Indication Action/Date Viragen Inc. (AMEX:VRA) Multiferon Multisubtype, natural human alpha interferon Various diseases Drug was approved in the Philippines and Chile for the secondline treatment of any diseases in which recombinant interferon therapy failed (4/25) Viragen Inc. (AMEX:VRA) Multiferon Multisubtype, human alpha interferon derived from white blood cells Malignant melanoma Filed for approval in Sweden to expand labeling to include firstline adjuvant treatment, following dacarbazine after surgical removal of tumors (2/4) Viventia Biotech Inc. (Canada; TSE:VBI) Proxinium Antibody fragment conjugated with a cancer-killing payload Head and neck cancer The product was granted orphan designation in Europe in that indication by the EMEA (6/1) Xechem Niprisan International (Nicosan/ Inc. (OTC BB:XKEM) Hemoxin) A phytopharmaceutical drug; a composition of four traditional plants Sickle cell disease The EMEA granted orphan designation to the product in the European Union (10/4) Xenova Group plc (UK; XNVA) TransMID (SOT-107) Modified diphtheria toxin conjugated to transferrin Glioma Partner Sosei Co. Ltd. was granted orphan drug status in that indication in Japan (2/14) York Pharma plc (UK; AIM:YRK) Abasol (abafungin) Broad-spectrum antifungal and antibacterial agent Dermatomycoses Filed for approval in the UK as the first step for seeking approval throughout Europe (7/29) Notes: * Privately held. MAA = Marketing authorization application; MRP = Mutual Recognition Procedure; EMEA = European Medicines Agency. Unless otherwise noted, the stock symbols listed for public companies are on the Nasdaq market. AIM = Alternative Investment Market; AMEX = American Stock Exchange; ASX = Australian Stock Exchange; CSE = Copenhagen Stock Exchange; LSE = London Stock Exchange; NYSE = New York Stock Exchange; OTC BB = Over-theCounter Bulletin Board; TSE = Toronto Stock Exchange. 402 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 BIOWORLD ® R E P O R T C A R D F O R WA L L S T R E E T Methodology Used To Evaluate Underwriters’ Performance BioWorld ranked the underwriters of 2005’s public offerings, both initial and follow-on, in two basic ways. First, the underwriters were ranked on the total amount of gross proceeds raised in both initial and follow-on public offerings combined. If an underwriting firm acted as the sole placement agent for an institutional offering then that firm was credited as “lead” underwriter. If more than one firm acted as placement agent then each was considered to be a co-manager, and credited as such for the purpose of calculating underwriters’ performance. For analysis on a “Full Credit To Lead” basis, BioWorld applied the total gross proceeds raised in IPOs and follow-on offerings to the lead underwriter for those offerings. For each underwriter cited, the graphs also indicate the total number of public offerings in which a particular underwriter acted as the lead underwriter. For analysis on a “Full Credit To All” basis, BioWorld applied the total gross proceeds raised in all types of public offerings to each underwriter of that offering. Secondly, BioWorld singled out the initial public offerings only and then analyzed underwriter performance. The underwriters were again ranked on both a “Full Credit To Lead” basis and a “Full Credit To All” basis (as described above). The graphs also indicate the total number of IPOs in which a particular underwriter acted as the lead underwriter, as well as the total number of IPOs in which that same underwriter acted as either lead or co-manager. In addition, BioWorld then analyzed the after-market performance of the IPOs and ranked the underwriters accordingly. Here, again, underwriters were ranked on both a “Full Credit To Lead” basis and a “Full Credit To All” basis. The after-market performance compared the share (or unit) price at the IPO with the share (or unit) price at the end of the calendar year (12/31/05), expressed as percent change. If one particular underwriter acted as either lead or co-manager in more than one IPO, BioWorld calculated the average percent change for those offerings. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 405 Top 10 Underwriters: All Public Offerings; Full Credit To Lead Underwriters, Ranked By Gross Proceeds Gross Proceeds ($M) Underwriter (Number of Offerings As Lead) 0 406 200 400 600 800 1,000 1,002 UBS Investment Bank (15) Morgan Stanley & Co. (10) 929 Merrill Lynch & Co. (7) 879 762 Goldman Sachs & Co. (6) JP Morgan Securities (9) 662 Bear, Stearns & Co. (7) 567 Lehman Brothers (6) 487 SG Cowen & Co. (9) 479 CIBC World Markets (9) Deutsche Bank Securities (4) 1,200 403 315 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Other Underwriters Of All Public Offerings For 2005: Full Credit To Lead Underwriters, Ranked By Gross Proceeds Underwriter (Number Of Offerings As Lead Underwriter) Gross Proceeds (M) Piper Jaffray & Co. (4) Banc of America Securities (4) Credit Suisse First Boston (3) Thomas Weisel Partners (2) Pacific Growth Equities (3) WR Hambrecht + Co. (3) Adams Harkness (1) Citigroup (1) Lazard Capital Markets (2) C.E. Unterberg, Towbin (1) ThinkEquity Partners (1) Robert W. Baird & Co. (1) Needham & Co. (1) Wachovia Capital Markets (1) Punk Ziegel & Co. (1) Jefferies & Co. (1) First Dunbar Securities (1) Ferris, Baker Watts (1) $281.7 $236.4 $218.8 $120.6 $93.3 $90.2 $86.3 $86.3 $76.6 $32.0 $32.0 $31.5 $23.3 $21.3 $20.2 $19.2 $17.3 $8.8 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 407 Top 10 Underwriters: All Public Offerings; Full Credit To All Underwriters, Ranked By Gross Proceeds Gross Proceeds ($M) Underwriter (Number Of Offerings As Lead/Number Of Offerings As Lead Or CoManager) 0 408 250 500 750 1,000 1,250 1,262 JP Morgan Securities (9/14) SG Cowen & Co. (9/16) 1,206 UBS Investment Bank (15/16) 1,178 1,104 Piper Jaffray & Co. (4/13) CIBC World Markets (9/18) 935 Morgan Stanley & Co. (10/10) 929 Lazard Capital Markets (2/13) 916 879 Merrill Lynch & Co. (7/7) Goldman, Sachs & Co. (6/7) Bear, Stearns & Co. (7/8) 1,500 827 702 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Other Underwriters Of All Public Offerings For 2005: Full Credit To All Underwriters, Ranked By Gross Proceeds Underwriter (Number Of Offerings As Lead Underwriter/Number Of Offerings As Lead Or Co-Manager) Gross Proceeds (M) Lehman Brothers (6/7) Needham & Co. (1/1 1) Banc of America Securities (4/6) First Albany Capital (0/4) Pacific Growth Equities (3/8) Thomas Weisel Partners (2/6) Lerrink Swann & Co. (0/4) Deutsche Bank Securities (4/4) JMP Securities (0/3) Wachovia Capital Markets (1/2) Credit Suisse First Boston (3/3) BMO Nesbitt Burns (0/2) Harris Nesbitt (0/2) Jefferies & Co. (1/3) Friedman, Billings, Ramsey (0/2) Punk Ziegel & Co. (1/2) A.G. Edwards (0/2) WR Hambrecht + Co. (3/3) C.E. Unterberg, Towbin (1/2) Robert W. Baird & Co. (1/2) Adams Harkness (1/1) Citigroup (1/1) D.A. Davidson & Co. (0/1) Brean Murray & Co. (0/1) Oppenheimer & Co. (0/1) William Blair & Co. (0/2) Fortis Securities (0/1) Wells Fargo Securities (0/1) First Associates Investments (0/1) GMP Securities (0/1) Orion Securities (0/1) Granite Financial Group (0/1) Morgan Joseph & Co. (0/1) ThinkEquity Partners (1/1) Merriman Curhan Ford & Co. (0/1) Legg Mason Wood Walker (0/1) $638.0 $632.9 $569.2 $540.6 $446.7 $316.2 $316.0 $315.2 $260.9 $223.7 $218.8 $152.3 $132.8 $132.6 $1 15.2 $101.4 $90.3 $90.2 $88.2 $86.7 $86.3 $86.3 $86.3 $81.2 $81.2 $79.9 $61.2 $61.2 $58.7 $58.7 $58.7 $51.8 $51.8 $32.0 $32.0 $28.9 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 409 Other Underwriters Of All Public Offerings For 2005: Full Credit To All Underwriters, Ranked By Gross Proceeds (Continued) Underwriter (Number Of Offerings As Lead Underwriter/Number Of Offerings As Lead Or Co-Manager) Gross Proceeds (M) Susquehanna Financial (0/1) GunnAllen Financial (0/2) Delafield Hambrecht (0/1) SunTrust Robinson, Humphrey (0/1) Baker Watts Stifel (0/1) Nicolaus & Co. (0/1) First Dunbar Securities (1/1) Ferris, Baker Watts (1/1) Maxim Group (0/1) $28.9 $28.0 $23.3 $23.3 $19.2 $19.2 $17.3 $8.8 $8.8 410 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Top 10 Underwriters: Initial Public Offerings; Full Credit To Lead Underwriters, Ranked By Gross Proceeds Gross Proceeds ($M) Underwriter (Number Of Offerings As Lead) 0 50 100 150 200 Merrill Lynch & Co. (2) 202 Banc of America Securities (2) 128 108 Morgan Stanley & Co. (2) Lehman Brothers (2) 102 UBS Investment Bank (2) 101 SG Cowen & Co. (2) 90 60 Credit Suisse First Boston (1) Pacific Growth Equities (1) 300 266 JP Morgan Securities (4) Deutsche Bank Securities (1) 250 53 48 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 411 Other Underwriters Of 2005’s Initial Public Offerings; Full Credit To Lead Underwriters, Ranked By Gross Proceeds Underwriter (Number Of IPOs As Lead Or Co-lead Underwriter) Gross Proceeds (M) Bear, Stearns & Co. (1) CIBC World Markets (1) C.E. Unterberg, Towbin (1) ThinkEquity Partners (1) WR Hambrecht + Co. (1) First Dunbar Securities (1) Jefferies & Co. (1) $42.0 $37.3 $32.0 $32.0 $28.9 $17.3 $19.2 412 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Underwriter (Number Of IPOs As Lead/Number Of IPOs As Lead Or Co-Manager) Top 10 Underwriters: Initial Public Offerings; Full Credit To All Underwriters, Ranked By Gross Proceeds Gross Proceeds ($M) 0 50 100 150 200 250 300 Lazard Capital Markets (0/5) JP Morgan Securities (4/4) 266 Merrill Lynch & Co. (2/2) 202 192 Pacific Growth Equities (1/3) Lerrink Swann & Co. (0/2) 171 Banc of America Securities (2/2) 128 CIBC World Markets (1/3) 120 Piper Jaffray & Co. (0/2) 115 Thomas Weisel Partners (0/2) 115 Morgan Stanley & Co. (2/2) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 108 413 Other Underwriters Of 2005’s Initial Public Offerings; Full Credit To All Underwriters, Ranked By Gross Proceeds Underwriter (Number Of IPOs As Lead/Number Of IPOs As Lead Or Co-Manager) Gross Proceeds (M) Lehman Brothers (2/2) UBS Investment Bank (2/2) BMO Nesbitt Burns (0/1) SG Cowen & Co. (2/2) A.G. Edwards (0/2) Needham & Co. (0/2) Credit Suisse First Boston (1/1) Deutsche Bank Securities (1/1) Bear, Stearns & Co. (1/1) William Blair & Co. (0/1) C.E. Unterberg, Towbin (1/1) ThinkEquity Partners (1/1) Merriman Curhan Ford & Co. (0/1) WR Hambrecht + Co. (1/1) Legg Mason Wood Walker (0/1) Susquehanna Financial (0/1) Jefferies & Co. (1/1) Baker Watts Stifel (0/1) GunnAllen Financial (0/1) JMP Securities (0/1) Nicolaus & Co. (0/1) First Dunbar Securities (1/1) $102.2 $101.2 $91.1 $90.3 $90.3 $84.0 $60.4 $52.5 $42.0 $37.3 $32.0 $32.0 $32.0 $28.9 $28.9 $28.9 $19.2 $19.2 $19.2 $19.2 $19.2 $17.3 414 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Top 10 Underwriters: Initial Public Offerings: After-Market Performance; Full Credit To Lead Underwriters Underwriter (Number Of Offerings as Lead) Percent Change In Stock Price Post-IPO To Year-End (25) 0 25 50 75 125 106 CIBC World Markets (1) 75 Banc of America Securities (2) 71 Deutsche Bank Securities (1) 31 Morgan Stanley & Co. (2) Merrill Lynch & Co. (2) 19 17 Pacific Growth Equities (1) (6) SG Cowen & Co. (2) JP Morgan Securities (4) 100 (15) UBS Investment Bank (2) (20) Credit Suisse First Boston (1) (20) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 415 Other Underwriters Of 2005’s Initial Public Offerings: After-Market Performance OF IPOS; Full Credit To Lead Underwriters Underwriter (Number Of IPOs As Lead/Number Of IPOs As Lead Or Co-Manager) Percentage Change In Stock Price Post-IPO To Year-End C.E. Unterberg, Towbin (1) ThinkEquity Partners (1) Lehman Brothers (2) Jefferies & Co. (1) Bear, Stearns & Co. (1) First Dunbar Securities (1) WR Hambrecht + Co. (1) -22% -22% -27% -37% -42% -55% -57% 416 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Top 10 Underwriters: Initial Public Offerings: After-Market Performance; Full Credit To All Underwriters Underwriter (Number Of Offerings as Lead) Percent Change In Stock Price Post-IPO To Year-End (10) 15 40 65 90 106 William Blair & Co. (0/1) 75 Banc of America Securities (2/2) 71 Deutsche Bank Securities (1/1) Pacific Growth Equities (1/3) 44 BMO Nesbitt Burns (0/1) 43 34 Lazard Capital Markets (0/5) 31 Morgan Stanley & Co. (2/2) 19 Merrill Lynch & Co. (2/2) 15 CIBC World Markets (1/3) SG Cowen & Co. (2/2) 115 (6) BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 417 Other Underwriters: Initial Public Offerings: After-Market Performance; Full Credit To All Underwriters Underwriter (Number Of IPOs As Lead/Number Of IPOs As Lead Or Co-Manager) Percentage Change In Stock Price Post-IPO To Year-End A.G. Edwards (0/2) Lerrink Swann & Co. (0/2) JP Morgan Securities (4/4) Piper Jaffray & Co. (0/2) Thomas Weisel Partners (0/2) UBS Investment Bank (2/2) Credit Suisse First Boston (1/1) C.E. Unterberg, Towbin (1/1) ThinkEquity Partners (1/1) Merriman Curhan Ford & Co. (0/1) JMP Securities (0/1) Lehman Brothers (2/2) Needham & Co. (0/2) Jefferies & Co. (1/1) Baker Watts Stifel (0/1) GunnAllen Financial (0/1) Nicolaus & Co. (0/1) Bear, Stearns & Co. (1/1) First Dunbar Securities (1/1) Legg Mason Wood Walker (0/1) Susquehanna Financial (0/1) WR Hambrecht + Co. (1/1) -13% -13% -15% -17% -17% -20% -20% -22% -22% -22% -24% -27% -36% -37% -37% -37% -37% -42% -55% -57% -57% -57% 418 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 BIOWORLD ® S T O C K PERFORMANCE 2005 Biotechnology Stock Report Company Symbol 12/31/04* 3/31/05 6/30/05 9/30/05 12/30/05 Aastrom Biosciences Abgenix Acadia Pharma Accelrys Access Pharma Acusphere Adolor Advancis Pharma Aeolus Pharma AEterna Zentaris Affymetrix Albany Molecular Alexion Pharma Alkermes Alliance Pharma Allos Therapeutics Alnylam Pharma Alteon Amgen Amylin Pharma Anadys Pharma Antigenics Aphton Aradigm Arena Pharma Ariad Pharma ArQule Array BioPharma Aspreva AtheroGenics AutoImmune Auxilium Pharma Avanir Avant Avax AVI BioPharma Avigen Axonyx BioCryst Pharma Biogen Idec BioMarin Pharma Biomira Biopure BioTime Boston Life Sciences Bruker BioSciences CancerVax Cardiovascular Bio Carrington Lab Celera Genomics ASTM ABGX ACAD ACCL AKC ACUS ADLR AVNC AOLS AEZS AFFX AMRI ALXN ALKS ALLP ALTH ALNY ALT AMGN AMLN ANDS AGEN APHT ARDM ARNA ARIA ARQL ARRY ASPV AGIX AIMM AUXL AVN AVAN AVXT AVII AVGN AXYX BCRX BIIB BMRN BIOM BPUR BTIM BLSI BRKR CNVX CVBT CARN CRA 1.42 10.34 6.77 7.80 3.54 6.13 9.92 3.82 1.25 6.26 36.55 1 1.14 25.20 14.09 0.19 2.4 7.47 1.31 64.15 23.36 7.49 10.12 3.1 1 1.73 6.70 7.43 5.79 9.52 1 1.00 23.56 0.88 8.85 3.41 2.01 0.31 2.35 3.26 6.20 5.78 66.61 6.39 2.41 0.59 1.51 2.85 4.03 10.85 10.00 6.13 13.75 2.08 7.00 6.90 5.93 2.49 5.41 9.92 3.70 0.70 5.12 42.81 10.28 21.67 10.38 0.17 2.06 7.35 0.59 58.21 17.49 7.36 6.70 1.27 6.10 5.05 5.60 4.69 7.01 14.55 13.09 1.00 5.98 2.20 1.63 0.36 2.50 2.79 1.23 4.61 34.51 5.15 1.86 1.98 1.13 2.50 3.52 6.59 1 1.00 5.16 10.25 3.12 8.58 8.40 4.95 1.85 4.77 9.25 1.72 0.73 4.61 53.92 14.00 23.04 13.22 0.20 2.18 7.30 0.22 60.46 20.93 9.16 5.41 0.74 5.30 6.82 6.66 6.48 6.30 15.49 15.98 0.87 4.77 2.80 1.17 0.28 2.32 3.08 1.33 5.08 34.45 7.48 1.72 1.32 0.58 2.10 3.99 2.85 7.60 4.50 10.97 2.35 12.68 1 1.37 6.76 0.88 5.44 10.68 1.41 1.12 4.80 46.23 12.18 27.65 16.80 0.1 1 2.44 1 1.30 0.30 79.67 34.79 10.67 5.42 0.63 5.35 9.90 7.43 7.83 7.18 14.26 16.03 0.91 4.98 3.09 1.30 0.31 2.64 2.78 1.15 9.78 39.48 8.73 1.38 1.1 1 0.43 2.1 1 4.38 3.44 8.80 4.21 12.13 2.1 1 21.49 9.85 8.03 0.52 5.34 14.60 1.38 0.95 5.10 47.75 12.15 20.25 19.12 0.09 2.15 13.36 0.18 78.86 39.92 8.80 4.76 0.34 0.73 14.21 5.85 6.12 7.01 15.72 20.01 0.92 5.50 3.44 1.88 0.25 3.45 3.03 0.83 16.75 45.28 10.78 1.40 0.78 0.31 2.23 4.86 1.38 4.55 4.73 10.96 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 % YTD 48.6 107.8 45.5 2.9 -85.3 -12.9 47.2 -63.9 -24.0 -18.5 30.6 9.1 -19.6 35.7 -52.6 -10.4 78.8 -86.3 22.9 70.9 17.5 -53.0 -89.1 -57.8 1 12.1 -21.3 5.7 -26.4 42.9 -15.1 4.5 -37.9 0.9 -6.5 -19.4 46.8 -7.1 -86.6 189.8 -32.0 68.7 -41.9 32.2 -79.5 -21.8 20.6 -87.3 -54.5 -22.8 -20.3 421 2005 Biotechnology Stock Report (Continued) Company Symbol Celgene CELG Cell Genesys CEGE Cell Therapeutics CTIC Cellegy Pharma CLGY CEL-SCI CVM Cephalon CEPH Cepheid CPHD Cerus CERS Chiron CHIR Cholestech CTEC Ciphergen CIPHE CollaGenex Pharma CGPI Columbia Laboratories CBRX CombiMatrix Group CBMX Compugen CGEN Connetics CNCT Corautus Genetics VEGF Corcept Therapeutics CORT Corgentech CGTK Cortex Pharma COR CoTherix CTRX Critical Therapeutics CRTX Crucell CRXL Cubist Pharma CBST CuraGen CRGN Curis CRIS CV Therapeutics CVTX Cyanotech CYAN Cygnus CYGT Cypress Bioscience CYPB Cytogen CYTO Cytokinetics CYTK CytRx CYTR deCODE genetics DCGN Deltagen DGEN Dendreon DNDN DepoMed DEPO Digene DIGE Discovery Labs DSCO Discovery Partners DPII Diversa DVSA DOR BioPharma DOR DOV Pharma DOVP Draxis Health DRAX DURECT DRRX DUSA Pharma DUSA Dyax DYAX Dynavax DVAX Embrex EMBX Emisphere EMIS Encysive Pharma ENCY EntreMed ENMD Enzo Biochem ENZ 422 12/31/04* 3/31/05 6/30/05 9/30/05 12/30/05 % YTD 26.52 8.10 8.14 2.87 0.60 50.88 9.94 2.95 33.33 8.20 4.30 7.34 2.65 3.97 5.15 24.29 5.38 6.25 8.28 2.71 1 1.92 8.00 13.77 1 1.83 7.16 5.22 23.00 1.44 0.12 14.06 1 1.52 10.25 1.40 7.81 0.07 10.78 5.40 26.15 7.93 4.71 8.74 0.64 18.05 4.96 3.28 14.3 7.22 8.00 13.26 4.02 9.93 3.24 19.47 34.05 4.53 3.59 1.62 0.65 46.83 9.67 3.07 35.06 10.08 2.77 4.67 1.91 2.22 4.01 25.29 4.61 4.54 2.32 2.23 6.62 6.79 13.05 10.62 4.16 3.58 20.36 1.22 0.17 9.14 5.79 6.56 0.37 5.70 0.16 5.45 3.94 20.75 5.63 3.20 4.98 0.39 13.68 5.15 3.64 8.73 3.22 4.67 1 1.72 3.67 10.22 2.10 14.42 40.70 5.35 2.71 1.63 0.52 39.8 7.34 4.43 34.89 1 1.27 1.91 7.61 3.15 2.34 3.20 17.64 4.17 5.76 2.60 2.35 10.19 7.02 24.01 13.17 5.14 3.90 22.42 1.18 1.40 13.20 5.23 6.94 0.91 9.39 0.1 1 5.23 4.37 27.68 7.29 2.86 5.21 0.32 18.66 4.97 5.09 9.30 4.71 4.80 1 1.15 4.02 10.81 2.31 17.93 54.32 5.48 2.86 1.43 0.47 46.42 7.39 8.86 43.65 10.08 1.85 9.92 3.76 1.66 3.31 16.91 4.45 5.00 2.36 2.37 13.95 9.42 26.81 21.54 4.95 4.59 26.75 0.96 1.57 5.41 4.04 8.14 0.97 8.39 0.24 6.71 6.48 28.5 6.45 3.22 5.79 0.33 16.98 4.62 6.85 10.6 5.59 6.70 1 1.25 4.50 1 1.78 2.39 15.36 64.80 5.93 2.18 0.52 0.49 64.74 8.78 10.15 44.44 9.92 1.18 12.07 4.65 1.37 4.26 14.45 4.16 3.65 2.45 2.28 10.58 7.18 25.60 21.24 3.08 3.55 24.73 0.65 0.15 5.78 2.74 6.52 1.03 8.26 0.40 5.42 6.00 29.17 6.69 2.65 4.80 0.27 14.68 4.33 5.07 10.77 5.27 4.21 13.86 4.34 7.88 1.94 12.42 144.3 -26.8 -73.2 -81.9 -18.3 27.2 -1 1.7 244.1 33.3 21.0 -72.6 64.4 75.5 -65.5 -17.3 -40.5 -22.7 -41.6 -70.4 -15.9 -1 1.2 -10.3 85.9 79.5 -57.0 -32.0 7.5 -54.9 25.0 -58.9 -76.2 -36.4 -26.4 5.8 -100.0 -49.7 1 1.1 1 1.5 -15.6 -43.7 -45.1 -57.8 -18.7 -12.7 54.6 -24.7 -27.0 -47.4 4.5 8.0 -20.6 -40.1 -36.2 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Stock Report (Continued) Company Symbol 12/31/04* 3/31/05 6/30/05 9/30/05 12/30/05 % YTD Enzon Pharma EPIX Pharma Ergo Science EXACT Sciences eXegenics Exelixis Favrille Flamel Technologies Genaera Gene Logic Genelabs Genentech Generex Biotech Genitope Gen-Probe Genta GenVec Genzyme Geron Gilead Sciences GPC Biotech GTC Biotherapeutics GTx Hana Bioscience Helix Biomesic Hemispherx Human Genome Sci Icagen ICOS Idenix Pharma IDEXX Laboratories ImClone Systems Immtech International ImmuCell Immucor Immune Response Immunicon ImmunoGen Immunomedics Incyte Indevus Pharma Inhibitex Inovio Biomedical Insite Vision Insmed Inspire Pharma Integra LifeSciences Interleukin Genetics InterMune IntraBiotics Pharma Introgen Therapeutics Invitrogen Isis Pharmaceuticals ENZN EPIX ERGO EXAS EXEG EXEL FVRL FLML GENR GLGC GNLBD DNA GNBT GTOP GPRO GNTA GNVC GENZ GERN GILD GPCB GTCB GTXI HBX HXBM HEB HGSI ICGN ICOS IDIX IDXX IMCL IMM ICCC BLUD IMNR IMMC IMGN IMMU INCY IDEV INHX INO ISV INSM ISPH IART ILI ITMN IBPI INGN IVGN ISIS 13.72 17.91 2.44 3.83 0.34 9.50 7.00 19.49 3.42 3.68 6.00 54.44 0.75 17.04 45.21 1.76 1.63 58.07 7.97 34.99 14.21 1.52 13.49 1.90 1.75 12.02 5.90 8.00 28.28 17.15 54.59 46.08 1 1.99 7.16 23.51 1.61 6.98 8.84 3.04 9.99 5.96 8.04 3.94 0.88 2.20 16.77 36.93 3.55 13.26 4.08 8.44 67.13 5.90 10.19 7.00 2.22 3.57 0.45 6.78 5.08 12.94 2.28 3.14 3.00 56.61 0.54 12.50 44.56 1.13 1.73 57.24 6.1 1 35.80 1 1.53 1.05 9.10 1.65 1.55 1.50 9.22 6.36 22.46 19.85 54.16 34.5 12.42 4.26 30.19 0.78 5.89 5.23 2.43 6.83 2.78 6.09 3.42 0.49 0.85 8.16 35.22 3.65 1 1.00 3.60 7.89 69.20 3.87 6.48 8.85 2.39 2.28 0.36 7.43 4.25 18.1 1 1.70 3.31 2.50 80.28 0.63 12.84 36.23 1.18 1.84 60.09 7.74 43.99 1 1.18 1.68 9.94 2.25 1.50 1.87 1 1.58 7.85 21.17 21.68 62.33 30.97 1 1.02 4.52 28.95 0.65 5.08 5.79 1.71 7.15 2.56 7.56 3.1 1 0.65 0.98 8.42 29.20 3.05 13.04 3.50 6.44 83.29 3.91 6.60 7.70 1.29 1.82 0.40 7.65 4.55 18.7 1.92 4.89 3.20 84.21 0.67 6.94 49.45 1.50 2.05 71.64 10.27 48.76 12.64 1.39 9.31 4.25 1.03 1.70 13.59 6.75 27.62 25.10 66.88 31.45 1 1.66 5.01 27.44 0.46 3.93 7.34 2.05 4.70 2.88 10.18 2.72 0.64 1.34 7.60 38.26 3.75 16.55 3.66 5.22 75.23 5.05 7.40 4.04 0.93 2.21 0.41 9.42 4.05 18.88 1.50 3.35 1.85 92.5 0.83 7.95 48.79 1.46 1.65 70.78 8.61 52.57 12.33 1.64 7.56 5.87 0.78 2.17 8.56 6.45 27.63 17.1 1 71.98 34.24 6.94 5.25 23.36 0.08 3.43 5.13 2.92 5.34 5.38 8.40 2.27 0.83 1.92 5.10 35.46 5.35 16.76 3.61 5.27 66.72 5.23 -46.1 -77.4 -61.9 -42.3 20.6 -0.8 -42.1 -3.1 -56.1 -9.0 -69.2 69.9 10.7 -53.3 7.9 -17.0 1.2 21.9 8.0 50.2 -13.2 7.9 -44.0 208.9 -55.4 -81.9 45.1 -19.4 -2.3 -0.2 31.9 -25.7 -42.1 -26.7 -0.6 -95.0 -50.9 -42.0 -3.9 -46.5 -9.7 4.5 -42.4 -5.7 -12.7 -69.6 -4.0 50.7 26.4 -1 1.5 -37.6 -0.6 -1 1.4 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 423 2005 Biotechnology Stock Report (Continued) Company Symbol 12/31/04* 3/31/05 6/30/05 9/30/05 12/30/05 % YTD ISTA Pharmaceuticals Keryx Biopharmac Kosan Biosciences La Jolla Pharma Large Scale Biology Lexicon Genetics LifeCell Lifecore Biomedical Ligand Pharma MacroChem Manhattan Pharma MannKind Martek Biosciences Matritech Maxygen Medarex MedImmune Memory Pharma Metabasis MGI Pharma Millennium Pharma Miravant Medical Momenta Pharma Monogram Biosci Myogen Myriad Genetics Nabi Biopharma Nanogen Nastech Pharma Nektar Therapeutics NeoPharm NeoRx Neose Technologies Neurobiological Tech. Neurochem Neurocrine Biosci Neurogen New River Pharma NitroMed North American Sci Northfield Labs Northwest Bioth Novavax NPS Pharma Nuvelo Onyx Pharma OraSure Technologies Orchid Biosciences Ortec Intl. Oscient Pharma OSI Pharma Osteotech OXiGENE ISTA KERX KOSN LJPCD LSBC LEXG LIFC LCBM LGND MACM MHA MNKD MATK MZT MAXY MEDX MEDI MEMY MBRX MOGN MLNM MRVT MNTA MGRM MYOG MYGN NABI NGEN NSTK NKTR NEOL NERX NTEC NTII NRMX NBIX NRGN NRPH NTMD NASI NFLD NWBT NVAX NPSP NUVO ONXX OSUR ORCH ORTN OSCI OSIP OSTE OXGN 10.12 1 1.57 6.93 8.35 6.30 7.76 10.22 1 1.26 1 1.64 0.85 0.97 15.75 51.20 1.06 12.79 10.78 27.1 1 5.32 7.25 28.01 12.14 1.01 7.06 0.73 8.07 22.51 14.65 7.36 12.10 20.24 12.51 2.09 6.72 4.42 17.53 49.3 9.36 14.96 26.65 5.39 22.55 0.04 3.26 18.28 9.85 32.39 6.72 1 1.50 0.97 3.65 74.85 5.50 5.50 9.88 13.36 4.10 3.50 4.50 5.1 1 8.95 17.81 5.73 16.37 1.55 14.23 58.19 1.02 8.58 7.13 23.81 4.38 3.40 25.27 8.42 0.85 8.47 2.39 7.89 18.39 12.48 3.48 9.88 13.94 7.77 0.99 2.58 3.33 1 1.91 38.06 7.08 25.50 17.31 3.60 1 1.25 0.26 1.41 12.62 6.50 31.35 7.36 1 1.76 0.73 2.34 41.34 3.77 4.08 8.32 13.20 5.28 4.00 4.85 4.94 15.81 10.91 6.95 10.08 1.49 10.05 37.96 0.70 6.86 8.30 26.72 1.85 3.15 21.75 9.27 0.51 19.77 2.48 6.99 15.65 15.23 3.84 14.23 16.83 9.99 0.60 3.15 3.02 10.05 42.06 6.82 29.99 19.45 2.07 14.31 0.18 1.32 1 1.35 7.73 23.82 9.98 10.79 0.35 2.65 41.01 3.68 4.54 6.64 15.76 7.27 3.80 4.15 3.97 21.63 12.09 10.14 2.14 1.30 13.69 35.13 0.63 8.29 9.52 33.65 2.71 5.83 23.24 9.33 0.39 27.25 2.35 23.50 21.86 13.10 3.21 14.15 16.95 12.40 0.92 2.35 3.81 12.67 49.19 6.88 47.94 18.00 2.62 12.90 0.17 1.75 10.1 1 9.60 24.97 9.45 8.50 0.35 2.12 29.24 5.73 5.27 6.36 14.64 4.42 3.70 0.1 1 3.65 19.04 16.22 1 1.15 0.02 1.25 1 1.26 24.64 0.53 7.50 13.87 34.98 2.28 8.00 17.15 9.70 0.19 22.04 1.87 30.09 20.79 3.40 2.61 14.71 16.46 10.79 0.75 1.93 3.59 14.31 62.73 6.56 51.84 13.95 2.15 13.40 0.10 3.85 1 1.84 8.1 1 28.8 8.83 7.65 0.19 2.27 28.04 5.01 3.97 -37.2 26.5 -36.2 -55.7 -98.3 -53.0 86.3 44.0 -4.2 -97.3 28.9 -28.5 -51.9 -50.0 -41.4 28.7 29.0 -57.1 10.3 -38.8 -20.1 -81.2 212.2 156.2 272.9 -7.6 -76.8 -64.5 21.6 -18.7 -13.7 -64.1 -71.3 -18.8 -18.4 27.2 -29.9 246.5 -47.7 -60.1 -40.6 150.0 18.1 -35.2 -17.7 -1 1.1 31.4 -33.5 -80.4 -37.8 -62.5 -8.9 -27.8 424 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Stock Report (Continued) OXIS Intl. Pain Therapeutics Palatin Technologies Peregrine Pharma Pharma Product Dev Pharmacopeia Drug Pharmacyclics Pharmion Pharmos Pharsight Praecis Pharma Progenics Pharma Protein Design Labs QLT Questcor Pharma Regeneration Regeneron Pharma Renovis Repligen Rigel Pharma Salix Pharma Sangamo Biosciences Santarus Savient Pharma SciClone Pharma Seattle Genetics Senomyx Sepracor Sequenom Serono SIGA Technologies Simulations Plus Sirna Therapeutics Solexa Sonus Pharma Spectrum Pharma StemCells Stratagene SuperGen Tanox Tapestry Pharma Targeted Genetics Telik Tercica Theravance Third Wave Tech Threshold Pharma Titan Pharma Transgenomic Trimeris Trinity Biotech Tripos Unigene United Therapeutics OXIS PTIE PTN PPHM PPDI PCOP PCYC PHRM PARS PHST PRCS PGNX PDLI QLTI QSC RTIX REGN RNVS RGEN RIGL SLXP SGMO SNTS SVNTE SCLN SGEN SNMX SEPR SQNM SRA SIGA SLP RNAI SLXA SNUS SPPI STEM STGN SUPG TNOX TPPH TGEN TELK TRCA THRX TWTI THLD TTP TBIO TRMS TRIB TRPS UGNE UTHR 0.55 7.21 2.66 1.17 41.29 5.97 10.47 42.21 1.42 0.95 1.90 17.16 20.66 16.08 0.53 10.48 9.21 14.38 2.88 24.42 7.64 6.00 9.04 2.71 3.70 6.53 8.28 59.37 1.44 16.32 1.66 5.56 3.17 17.59 3.53 6.66 4.23 7.75 7.05 15.2 0.97 1.55 19.14 10.00 17.9 8.60 7.00 3.22 1.15 14.17 2.96 5.33 2.25 45.15 0.35 5.08 2.34 1.47 48.45 5.04 8.03 29.00 0.63 1.70 1.05 16.81 15.99 12.86 0.61 10.31 5.1 1 8.07 1.70 16.04 16.49 4.00 4.86 2.69 2.84 5.14 1 1.91 57.41 1.06 18.15 1.28 4.65 2.95 9.04 2.64 5.97 3.15 8.81 4.86 9.60 0.61 0.61 15.08 7.63 18.25 5.76 5.99 2.22 0.57 1 1.26 2.54 4.15 1.76 45.7 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 0.32 6.75 1.75 0.96 46.86 4.05 7.51 23.20 2.45 1.75 0.52 20.86 20.21 10.42 0.64 6.26 8.36 15.27 2.17 19.92 17.66 3.57 4.10 4.41 4.49 5.36 16.51 60.01 1.16 15.99 1.08 3.94 1.75 6.80 3.51 4.20 4.20 8.69 4.94 1 1.72 0.46 0.81 16.25 8.58 17.00 3.93 8.25 1.83 0.68 9.99 6.50 3.71 1.70 48.20 0.37 6.29 2.30 1.00 57.51 3.57 9.02 21.81 2.14 1.74 0.47 23.71 28.00 7.67 0.54 8.17 9.49 13.53 3.12 23.77 21.25 4.39 6.21 3.77 5.64 5.25 17.03 58.99 0.96 16.45 1.06 3.71 4.40 5.85 4.25 4.96 5.52 9.01 6.30 14.65 0.37 0.68 16.36 1 1.28 21.04 4.95 13.65 1.77 1.00 15.34 7.40 4.20 2.91 69.80 0.26 6.76 3.26 0.93 61.95 3.56 3.55 17.77 2.01 1.36 4.00 25.01 28.44 6.36 1.04 7.15 15.90 15.30 4.00 8.36 17.58 4.03 5.30 3.74 2.32 4.72 12.12 51.6 0.68 19.86 0.95 5.18 3.03 10.07 5.03 4.23 3.45 10.04 5.05 16.37 0.31 0.49 16.99 7.17 22.52 2.98 14.45 1.43 1.06 1 1.49 8.16 2.93 4.41 69.12 -52.7 -6.2 22.6 -20.5 50.0 -40.4 -66.1 -57.9 41.5 43.2 1 10.5 45.7 37.7 -60.4 96.2 -31.8 72.6 6.4 38.9 -65.8 130.1 -32.8 -41.4 38.0 -37.3 -27.7 46.4 -13.1 -52.8 21.7 -42.8 -6.8 -4.4 -42.8 42.5 -36.5 -18.4 29.5 -28.4 7.7 -68.0 -68.4 -1 1.2 -28.3 25.8 -65.3 106.4 -55.6 -7.8 -18.9 175.7 -45.0 96.0 53.1 425 2005 Biotechnology Stock Report (Continued) Company Symbol Valentis VaxGen Vernalis Vertex Pharma ViaCell Vical Vion Pharma VioQuest Pharma Viragen ViroPharma Xcyte Therapies Xenogen XenoPort XOMA Limited Zonagen ZymoGenetics VLTS VXGN VNLS VRTX VIAC VICL VION VQPH VRA VPHM XCYT XGEN XNPT XOMA ZONA ZGEN 426 12/31/04* 3/31/05 6/30/05 9/30/05 12/30/05 % YTD 2.50 17.00 3.20 10.57 7.00 4.70 4.69 0.80 1.00 3.25 2.76 7.00 10.50 2.59 4.33 23.00 2.66 12.48 2.45 9.36 7.54 4.00 2.85 0.68 0.68 2.34 1.23 5.20 – 1.00 3.05 15.26 2.83 10.85 2.13 16.85 10.65 4.88 2.17 0.70 0.70 6.95 0.72 3.75 10.64 1.68 3.83 17.60 2.38 14.50 2.43 22.35 5.80 4.92 2.17 1.05 0.50 20.8 0.48 3.07 16.50 1.76 5.75 16.50 2.14 8.75 2.05 27.67 5.62 4.20 1.65 0.75 0.45 18.50 0.67 3.15 17.95 1.60 5.1 1 16.99 -14.4 -48.5 -35.9 161.8 -19.7 -10.6 -64.8 -6.3 -55.0 469.2 -75.7 -55.0 71.0 -38.2 18.0 -26.1 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 British Biotechnology Stock Report Company Symbol Acambis Ark Therapeutics Antisoma Cambridge Antibody Oxford Biomedica Pharmagene Phytopharm Protherics Provalis SkyePharma Vernalis Group ACM AKT ASM CAT OXB PGN PYM PTI PRO SKP VER 12/31/04 3/31/05 6/30/05 9/30/05 12/30/05 % YTD 251.5 16.25 85.00 721.00 17.50 31.00 235.00 65.75 8.62 65.00 88.50 237.25 23.00 109.50 661.00 20.00 26.00 122.50 49.25 5.88 54.00 69.50 220.50 18.52 103.00 643.50 33.50 21.50 85.00 58.50 3.38 55.50 62.75 238.00 20.80 104.75 744.00 45.75 23.40 51.35 54.75 5.25 41.00 73.25 208.75 19.05 103.00 698.00 30.25 16.00 53.00 82.75 1.70 50.50 61.00 -17.0 17.2 21.2 -3.2 72.9 -48.4 -77.4 25.9 -80.3 -22.3 -31.1 Public biotechnology companies are listed on the London Stock Exchange. Prices are denoted in pence. % YTD = Percent change in stock price between 12/31/04 and 12/30/05. BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 427 2005 Canadian Biotechnology Stock Report Company Symbol Adherex Technologies Angiotech Pharma AnorMED Bioniche Life Sciences Chromos Molecular ConjuChem Cangene Cardiome Pharma Ecopia Biosciences Hemosol IBEX Technologies ID Biomedical Inex Pharma Inflazyme Pharma Lorus Therapeutics Medicure Bioms Medical Neurochem Oncolytics Biotech Resverlogix Stressgen Biotech Theratechnologies YM Biosciences AHX ANP AOM BNC CHR CJC CNJ COM EIA HML IBT IDB IEX IZP LOR MPH MS NRM ONC RVX SSB TH YM 12/31/043* 3/31/05 6/30/05 9/30/05 12/30/05 % YTD 0.42 22.22 5.65 1.66 0.62 4.20 1 1.15 9.09 1.05 1.01 0.44 17.91 0.88 0.22 0.71 0.90 3.35 21.23 5.55 4.50 0.42 2.10 3.56 0.30 18.65 4.25 1.35 0.40 3.70 8.50 7.59 0.80 0.66 0.38 18.40 0.40 0.14 0.73 0.73 3.57 14.40 4.85 7.85 0.33 1.86 3.10 0.34 16.87 3.65 1.30 0.18 3.93 7.75 6.60 0.77 1.25 0.30 20.05 0.26 0.14 0.76 0.92 2.80 12.3 4.13 6.31 0.25 1.53 3.03 1.29 16.19 4.14 1.00 0.20 0.78 8.10 10.24 0.49 .90 0.23 34.84 0.12 0.13 0.74 1.16 2.84 14.65 4.48 7.55 0.35 1.24 3.49 0.96 15.34 4.77 0.70 0.16 1.09 10.20 1 1.72 0.55 0.08 0.29 34.99 0.14 0.12 0.31 1.56 2.52 16.59 5.24 6.80 0.56 1.07 3.66 128.6 -31.0 -15.6 -57.8 -74.2 -74.0 -8.5 28.9 -47.6 -92.1 -34.1 95.4 -84.1 -45.5 -56.3 73.3 -24.8 -21.9 -5.6 51.1 33.3 -49.0 2.8 Public biotechnology companies are listed on Canadian stock exchanges. Prices are denoted in Canadian dollars. YTD = Percent change in stock price between 12/31/04 and 12/30/05. 428 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Price Performance Of Biotechnology Stocks Ranked By Percent Change In Closing Price From 2005 Year-End (Or IPO Price For IPOs In 2005) Company Symbol 12/31/04* 12/30/05 % YTD I. STOCKS THAT GAINED VALUE Deltagen DGEN .07 ViroPharma VPHM 3.25 Myogen MYOG 8.07 New River Pharma NRPH 14.96 Cerus CERS 2.95 Momenta Pharma MNTA 7.06 Hana Bioscience HBX 1.90 BioCryst Pharma BCRX 5.78 Trinity Biotech TRIB 2.96 Vertex Pharma VRTX 10.57 Monogram Biosci MGRM 0.73 Northwest Bioth NWBT 0.04 Celgene CELG 26.52 Salix Pharma SLXP 7.64 Arena Pharma ARNA 6.70 Praecis Pharma PRCS 1.90 Abgenix ABGX 10.34 Threshold Pharma THLD 7.00 Questcor Pharma QSC 0.53 Unigene UGNE 2.25 LifeCell LIFC 10.22 Crucell CRXL 13.77 Cubist Pharma CBST 1 1.83 Alnylam Phama ALNY 7.47 Columbia Labs CBRX 2.65 Regeneron Pharma REGN 9.21 XenoPort XNPT 10.50 Amylin Pharma AMLN 23.36 Genentech DNA 54.44 BioMarin Pharma BMRN 6.39 CollaGenex Pharma CGPI 7.34 Durect DRRX 3.28 United Therapeutics UTHR 45.15 Interleukin Genetics ILI 3.55 Gilead Sciences GILD 34.99 Pharma Prod Dev PPDI 41.29 Aastrom Biosci ASTM 1.42 Adolor ADLR 9.92 AVI BioPharma AVII 2.35 Senomyx SNMX 8.28 Progenics Pharma PGNX 17.16 .40 18.50 30.09 51.84 10.15 22.04 5.87 16.75 8.16 27.67 1.87 0.10 64.8 17.58 14.21 4.00 21.49 14.45 1.04 4.41 19.04 25.6 21.24 13.36 4.65 15.90 17.95 39.92 92.50 10.78 12.07 5.07 69.12 5.35 52.57 61.95 2.1 1 14.60 3.45 12.12 25.01 471.40 469.23 272.86 246.52 244.07 212.18 208.95 189.79 175.68 161.78 156.16 150.00 144.34 130.10 1 12.09 1 10.53 107.83 106.43 96.23 96.00 86.30 85.91 79.54 78.85 75.47 72.64 70.95 70.89 69.91 68.70 64.44 54.57 53.09 50.70 50.24 50.04 48.59 47.18 46.81 46.38 45.75 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Company Symbol Acadia Pharma ACAD Human Genome Sci HGSI Lifecore Biomedical LCBM Pharsight PHST Aspreva ASPV Sonus Pharma SNUS Pharmos PARS Repligen RGEN Savient Pharma SVNTE Protein Design Labs PDLI Alkermes ALKS Chiron CHIR Biopure BPUR IDEXX Labs IDXX OraSure Techno OSUR Affymetrix AFFX Stratagene STGN MedImmune MEDI Manhattan Pharma MHA Medarex MEDX Neurocrine Biosci NBIX Cephalon CEPH Keryx Biopharma KERX InterMune ITMN Theravance THRX Cygnus CYGN Amgen AMGN Palatin Techno PTN Genzyme GENZ Serono SRA Nastech Pharma NSTK Cholestech CTEC Bruker BioSci BRKR eXegenics EXEG Novavax NVAX Zonagen ZONA Anadys Pharma ANDS Digene DIGE DepoMed DEPO Generex Biotech GNBT Metabasis Thera MBRX Albany Molecular AMRI Geron GERN 12/31/04* 12/30/05 6.77 5.90 1 1.26 0.95 1 1.00 3.53 1.42 2.88 2.71 20.66 14.09 33.33 0.59 54.59 6.72 36.55 7.75 27.1 1 0.97 10.78 49.3 50.88 1 1.57 13.26 17.9 0.12 64.15 2.66 58.07 16.32 12.10 8.20 4.03 0.34 3.26 4.33 7.49 26.15 5.40 0.75 7.25 1 1.14 7.97 9.85 8.56 16.22 1.36 15.72 5.03 2.01 4.00 3.74 28.44 19.12 44.44 0.78 71.98 8.83 47.75 10.04 34.98 1.25 13.87 62.73 64.74 14.64 16.76 22.52 0.15 78.86 3.26 70.78 19.86 14.71 9.92 4.86 0.41 3.85 5.1 1 8.80 29.17 6.00 0.83 8.00 12.15 8.61 % YTD 45.49 45.08 44.05 43.16 42.91 42.49 41.55 38.89 38.01 37.66 35.70 33.33 32.20 31.86 31.40 30.64 29.55 29.03 28.87 28.66 27.24 27.24 26.53 26.40 25.81 25.00 22.93 22.56 21.89 21.69 21.57 20.98 20.60 20.59 18.10 18.01 17.49 1 1.55 1 1.1 1 10.67 10.34 9.07 8.03 429 2005 Biotechnology Stock Report (Continued) 12/30/05 % YTD Company 4.02 45.21 1.52 15.20 23.00 14.38 7.81 5.79 0.88 13.26 8.04 7.80 1.63 3.41 4.34 48.79 1.64 16.37 24.73 15.30 8.26 6.12 0.92 13.86 8.40 8.03 1.65 3.44 7.96 7.92 7.89 7.70 7.52 6.40 5.76 5.70 4.55 4.52 4.48 2.95 1.23 0.88 I. STOCKS THAT LOST VALUE Large Scale Biology LSBC 6.30 MacroChem MCMP 0.73 Immune Response IMNR 1.61 Aphton APHT 3.1 1 CancerVax CNVX 10.85 Axonyx I AXYX 6.20 Alteon ALT 1.31 Access Pharma AKC 3.54 Hemispherx HEB 12.02 Cellegy Pharma CLGY 2.87 Miravant Medical MRVT 1.01 Ortec Intl ORTN 0.97 BioTime BTIM 1.51 EPIX Medical EPIX 17.91 Nabi Biopharma NABI 14.65 Cytogen CYTO 1 1.52 Xcyte Therapies XCYT 2.76 Cell Therapeutics CTIC 8.14 Ciphergen CIPHE 4.30 Neose Techno NTEC 6.72 Corgentech CGTK 8.28 Inspire Pharma ISPH 16.77 Genelabs Techno GNLBD 6.00 Targeted Genetics TGEN 1.55 Tapestry Pharma TPPH 0.97 Pharmacyclics PCYC 10.47 Rigel Pharma RIGL 24.42 CombiMatrix Group CBMX 3.97 Third Wave Techno TWTI 8.60 430 0.1 1 0.02 0.08 0.34 1.38 0.83 0.18 0.52 2.17 0.52 0.19 0.19 0.31 4.04 3.40 2.74 0.67 2.18 1.18 1.93 2.45 5.10 1.85 0.49 0.31 3.55 8.36 1.37 2.98 -98.25 -97.26 -95.03 -89.07 -87.28 -86.61 -86.26 -85.31 -81.95 -81.88 -81.19 -80.41 -79.47 -77.44 -76.79 -76.22 -75.72 -73.22 -72.56 -71.28 -70.41 -69.59 -69.17 -68.39 -68.04 -66.09 -65.77 -65.49 -65.35 Vion Pharma Nanogen NeoRx Advancis Pharma OSI Pharma Ergo Science QLT North American Sci Cypress Bioscience Pharmion DOR BioPharma Aradigm Memory Pharma CuraGen Genaera La Jolla Pharma Titan Pharma Helix Biomedix Viragen Xenogen Cyanotech Cardiovascular Bio Genitope Antigenics Lexicon Genetics Sequenom Oxis Intl Alliance Pharma Martek Biosciences Immunicon Matritech Dendreon VaxGen NitroMed Dynavax Techno Incyte Enzon Pharma Diversa Tripos GTx Discovery Partners SIGA Technologies Solexa Inovio Biomedical EXACT Sciences Favrille Company Emisphere Techno Gen-Probe GTC Biothera Tanox CV Therapeutics Renovis deCODE genetics ArQule AutoImmune Embrex Inhibitex Accelrys GenVec Avanir Symbol EMIS GPRO GTCB TNOX CVTX RNVS DCGN ARQL AIMM EMBX INHX ACCL GNVC AVN 12/31/04* Symbol VION NGEN NERX AVNC OSIP ERGO QLTI NASI CYPB PHRM DOR ARDM MEMY CRGN GENR LJPCD TTP HXBM VRA XGEN CYAN CVBT GTOP AGEN LEXG SQNM OXIS ALLP MATK IMMC MZT DNDN VXGN NTMD DVAX INCY ENZN DVSA TRPS GTXI DPII SIGA SLXA INO EXAS FVRL 12/31/04* 4.69 7.36 2.09 3.82 74.85 2.44 16.08 5.39 14.06 42.21 0.64 1.73 5.32 7.16 3.42 8.35 3.22 1.75 1.00 7.00 1.44 10.00 17.04 10.12 7.76 1.44 0.55 0.19 51.2 6.98 1.06 10.78 17.00 26.65 8.00 9.99 13.72 8.74 5.33 13.49 4.71 1.66 17.59 3.94 3.83 7.00 12/30/05 1.65 2.61 0.75 1.38 28.04 0.93 6.36 2.15 5.78 17.77 0.27 0.73 2.28 3.08 1.50 3.70 1.43 0.78 0.45 3.15 0.65 4.55 7.95 4.76 3.65 0.68 0.26 0.09 24.64 3.43 0.53 5.42 8.75 13.95 4.21 5.34 7.40 4.80 2.93 7.56 2.65 0.95 10.07 2.27 2.21 4.05 % YTD -64.82 -64.54 -64.1 1 -63.87 -62.54 -61.89 -60.45 -60.1 1 -58.89 -57.90 -57.81 -57.80 -57.14 -56.98 -56.14 -55.69 -55.59 -55.43 -55.00 -55.00 -54.86 -54.50 -53.35 -52.96 -52.96 -52.78 -52.73 -52.63 -51.88 -50.86 -50.00 -49.72 -48.53 -47.65 -47.38 -46.55 -46.06 -45.08 -45.03 -43.96 -43.74 -42.77 -42.75 -42.39 -42.30 -42.14 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 2005 Biotechnology Stock Report (Continued) Company Symbol Immtech Intl IMM ImmunoGen IMGN Biomira BIOM Corcept Thera CORT Santarus SNTS Maxygen MAXY Northfield Labs NFLD Connetics CNCT Pharmacopeia Drug PCOP EntreMed ENMD MGi Pharma MOGN XOMA Limited XOMA AuxiliumPharma AUXL Oscient Pharma OSCI Introgen Therapeu INGN SciClone Pharma SCLN ISTA Pharma ISTA Spectrum Pharma SPPI Cytokinetics CYTK Kosan Biosciences KOSN Enzo Biochem ENZ Vernalis VNLS NPS Pharma NPSP Orchid Biosciences ORCH Sangamo Biosci SGMO Biogen Idec BIIB Curis CRIS Regeneration Tech RTIX Neurogen NRGN MannKind MNKD SuperGen SUPG Tercica TRCA OXiGENE OXGN Seattle Genetics SGEN Dyax Corp. DYAX Cell Genesys CEGE ImmuCell ICCC CytRx CYTR Array BioPharma ARRY ZymoGenetics ZGEN ImClone Systems IMCL DUSA Pharma DUSA Aeolus Pharma AOLS Carrington Labs CARN Corautus Genetics VEGF Boston Life Sci BLSI 12/31/04* 1 1.99 8.84 2.41 6.25 9.04 12.79 22.55 24.29 5.97 3.24 28.01 2.59 8.85 3.65 8.44 3.70 10.12 6.66 10.25 6.93 19.47 3.20 18.28 1 1.50 6.00 66.61 5.22 10.48 9.36 15.75 7.05 10.00 5.50 6.53 7.22 8.10 7.16 1.40 9.52 23.00 46.08 14.30 1.25 6.13 5.38 2.85 12/30/05 6.94 5.13 1.40 3.65 5.30 7.50 13.40 14.45 3.56 1.94 17.15 1.60 5.50 2.27 5.27 2.32 6.36 4.23 6.52 4.42 12.42 2.05 1 1.84 7.65 4.03 45.28 3.55 7.15 6.56 1 1.26 5.05 7.17 3.97 4.72 5.27 5.93 5.25 1.03 7.01 16.99 34.24 10.77 0.95 4.73 4.16 2.23 % YTD -42.12 -41.97 -41.91 -41.60 -41.37 -41.36 -40.58 -40.51 -40.37 -40.12 -38.77 -38.22 -37.85 -37.81 -37.56 -37.30 -37.15 -36.49 -36.39 -36.22 -36.21 -35.94 -35.23 -33.48 -32.83 -32.02 -31.99 -31.77 -29.91 -28.51 -28.37 -28.30 -27.82 -27.72 -27.0 1 -26.79 -26.68 -26.43 -26.37 -26.13 -25.69 -24.69 -24.00 -22.84 -22.68 -21.75 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Company Symbol Ariad Pharma Encysive Pharma Peregrine Pharma Celera Genomics Millennium Pharma ViaCell Alexion Pharma icagen Avax Techno Trimeris Neurobiological Nektar Therap DOV Pharma AEterna Zentaris StemCells Neurochem CEL-SCI Nuvelo Compugen Genta Cortex Pharma Discovery Labs AtheroGenics Valentis NeoPharm GPC Biotech Sepracor Acusphere Insmed Draxis Health Cepheid IntraBiotics Pharma ISIS Pharma CoTherix Telik Onyx Pharma Vical Allos Therapeutics Critical Theraptcs Indevus Pharma Gene Logic Osteotech Transgenomic Myriad Genetics Avigen Simulations Plus ARIA ENCY PPHM CRA MLNM VIAC ALXN ICGN AVXT TRMS NTII NKTR DOVP AEZS STEM NRMX CVM NUVO CGEN GNTA COR DSCO AGIX VLTS NEOL GPCB SEPR ACUS INSM DRAX CPHD IBPI ISIS CTRX TELK ONXX VICL ALTH CRTX IDEV GLGC OSTE TBIO MYGN AVGN SLP 12/31/04* 7.43 9.93 1.17 13.75 12.14 7.00 25.20 8.00 0.31 14.17 4.42 20.24 18.05 6.26 4.23 17.53 0.60 9.85 5.15 1.76 2.71 7.93 23.56 2.50 12.51 14.21 59.37 6.13 2.20 4.96 9.94 4.08 5.90 1 1.92 19.14 32.39 4.70 2.40 8.00 5.96 3.68 5.50 1.15 22.51 3.26 5.56 12/30/05 5.85 7.88 0.93 10.96 9.70 5.62 20.25 6.45 0.25 1 1.49 3.59 16.46 14.68 5.10 3.45 14.31 0.49 8.1 1 4.26 1.46 2.28 6.69 20.01 2.14 10.79 12.33 51.60 5.34 1.92 4.33 8.78 3.61 5.23 10.58 16.99 28.80 4.20 2.15 7.18 5.38 3.35 5.01 1.06 20.79 3.03 5.18 % YTD -21.27 -20.64 -20.51 -20.29 -20.10 -19.71 -19.64 -19.38 -19.35 -18.91 -18.78 -18.68 -18.67 -18.53 -18.44 -18.37 -18.33 -17.66 -17.28 -17.05 -15.87 -15.64 -15.07 -14.40 -13.75 -13.23 -13.09 -12.89 -12.73 -12.70 -1 1.67 -1 1.52 -1 1.36 -1 1.24 -1 1.23 -1 1.08 -10.64 -10.42 -10.25 -9.73 -8.97 -8.91 -7.83 -7.64 -7.06 -6.83 431 2005 Biotechnology Stock Report (Continued) Company Symbol AVANT Immuno AVAN VioQuest Pharma VQPH Pain Therapeutics PTIE Insite Vision ISV Sirna Therapeutics RNAI Ligand Pharma LGND Integra LifeSciences IART Immunomedics IMMU Flamel Techno FLML ICOS ICOS Exelixis EXEL Immucor BLUD Invitrogen IVGN Idenix Pharma IDIX 432 12/31/04* 2.01 0.80 7.21 0.88 3.17 1 1.64 36.93 3.04 19.49 28.28 9.50 23.51 67.13 17.15 12/30/05 1.88 0.75 6.76 0.83 3.03 1 1.15 35.46 2.92 18.88 27.63 9.42 23.36 66.72 17.1 1 % YTD -6.47 -6.25 -6.24 -5.68 -4.42 -4.21 -3.98 -3.95 -3.13 -2.30 -0.84 -0.64 -0.61 -0.23 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 Tracking The Overall Performance Of The 279 Stocks In BioWorld’s Universe BioWorld Financial Watch has tracked the price performance of biotechnology and biotech-related stocks on a weekly basis since July 1994. Since Aug. 8, 1994, BioWorld Financial Watch also has published data indicating the average percent change of all the stocks listed on U.S. exchanges both on a week-to-week basis and on a year-to-date basis. For the stocks included in BioWorld Financial Watch’s 2005 stock indicator, see the list on page 421. The graph on page 435 plots the change in that indicator (the average percent change in the stocks, year to date) on a monthly basis throughout 2005. Of the 279 stocks included in the list, the average percent change between Dec. 31, 2004, and Dec. 30, 2005, was a loss of 2.09 percent (on a non-market-weighted basis). This average does not include securities traded on the Toronto Stock Exchange or London Stock Exchange. Of the 282 stocks included in the list, the average percent change between Dec. 31, 2003, and Dec. 31, 2004, was a gain of 2.5 percent Of the 261 stocks included in the 2003 list, the average percent change between Dec. 31, 2002, and Dec. 31, 2003, was a gain of 120.8 percent. Of the 274 stocks included in the 2002 list, the average percent change between Dec. 31, 2001, and Dec. 31, 2002, was a loss of 51.05 percent. Of the 280 stocks included in the list in 2001, the average percent change between Dec. 31, 2000, and Dec. 31, 2001, was a gain of 3.17 percent. Of the 279 stocks included in the list in 2000, the average percent change between Dec. 31, 1999, and Dec. 31, 2000, was a gain of 27.52 percent. By contrast, the stocks that were included in this list for calendar year 1999 did even better. They gained an average of 97.57 percent. The average change in 1998 was a loss of 1 1.53 percent. For 1997, it was a loss of 1.87 percent. Although 1998 and 1997 weren’t very good years for biotech stock per- BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 433 formance, 1996 was markedly better. The 286 stocks that were included in the list for the calendar year of 1996 gained an average of 17.94 percent. Also, a full 53 percent of the stocks either gained value in 1996 or ended the year unchanged. But 1995 was an outstanding year for biotech stocks. The 286 stocks that were included in the list for the calendar year of 1995 gained an average of 96.24 percent from the end of 1994 to the end of 1995; also, the vast majority of the stocks (81 percent) either gained value during 1995 or ended the year unchanged. The BioWorld Stock Indicator measures the average percent change year to date in biotech and biotech-related stocks that are covered weekly in BioWorld Financial Watch. The Friday closing price of each stock on the list is compared either to its 2004 closing price (12/31/04) or its IPO price (if the stock started trading in 2005) and expressed as a percent change. Then the percent changes for all stocks on the list are added and divided by the total number of stocks listed. Because these averages are not weighted in any way and do not take into account the market capitalization for each company on the list, they cannot be considered true indices. Instead, they serve as indicators of the sector’s performance. For comparison, we also have charted the performance in 2005 of a standard index, the Nasdaq Biotech Index. The index is market-value weighted, with the representation of each stock in the index being proportional to its closing price times the total number of shares outstanding, relative to the total market value of the index. ■ 434 BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 BioWorld Stock Indicator 2005 Average Percent Change YTD 9 6 3 0 -3 -6 -9 -12 -15 -18 -21 -24 -27 -30 12 1/1 1/2 2/1 2/2 3/1 3/2 4/8 4/2 5/6 5/2 6/3 6/1 7/1 7/1 7/2 8/1 8/2 9/9 9/2 10 10 11 11 12 12 12 / 31 4/ 8/ 1/ 5/ 1/ 5/ /2 2/ /2 0/ /2 7/ /2 5/ 9/ 2/ 6/ /2 3/ / 7/ / 21 / 4/ / 18 / 2/ / 16 / 30 /20 200 200 200 200 200 200 005 200 005 200 005 200 005 200 200 200 200 005 200 200 /20 200 /20 200 /20 /20 04 5 5 5 5 5 5 5 5 5 5 05 5 05 5 05 05 5 5 5 5 5 Date Nasdaq Biotech Index 2005 Average Percent Change YTD 860 840 820 800 780 760 740 720 700 680 660 640 620 600 12 1/1 1/2 2/1 2/2 3/1 3/2 4/8 4/2 5/6 5/2 6/3 6/1 7/1 7/1 7/2 8/1 8/2 9/9 9/2 10 10 11 11 12 12 12 /31 4/ 8/ 1/ 5/ 1/ 5/ /0 2/ /0 0/ /0 7/ /0 5/ 9/ 2/ 6/ /0 3/ /7/ /21 /4/ /18 /2/ /16 /30 /04 05 05 05 05 05 05 5 05 5 05 5 05 5 05 05 05 05 5 05 05 /05 05 /05 05 /05 /05 Date BIOWORLD® BIOTECHNOLOGY STATE OF THE INDUSTRY REPORT 2006 435