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August 2012 Volume 8, Number 8
www.drugdiscoverynews.com
Global News
6
Tools & Technology
12
what’s inside
Diagnostics16
Omics & Systems Biology
20
research & development
24
Contract Research Services
28
finance.........................................................3
Markets........................................................4
Editorial/commentary..............................10
products & services................................37
facts & figures..........................................38
Valeant all Surprising and sizable injection
smiles over BMS-AstraZeneca
diabetes partnership gets
boost with
OraPharma $7-billion
BMS’ acquisition of
Valeant acquires oral health
company for $312 million
Amylin Pharmaceuticals
By Kelsey Kaustinen
By Amy Swinderman
MONTREAL—Valeant
Pharmaceuticals
International Inc. recently announced
that it will acquire OraPharma, a specialty pharmaceutical company specializing in oral health, for approximately
$312 million. Valeant will acquire the
company from Water Street Healthcare
Partners, a private equity firm solely
valeant continued on page 8
SAN DIEGO—A diabetes partnership initiated
in 2007 by Bristol-Myers Squibb Co. (BMS)
and AstraZeneca PLC received a huge boost
last month in the unlikely form of a multibillion-dollar acquisition—of Amylin Pharmaceuticals Inc. by BMS for $31 per share in
cash, or approximately $5.3 billion.
The acquisition is pursuant to a cash tender
bms continued on page 26
BMS’ acquisition of Amylin is part of an ongoing diabetes alliance between BMS and AstraZeneca that will now
develop and commercialize Amylin’s portfolio of GLP-1 agonists for the treatment of type 2 diabetes.
Hiding in plain sight The life science DREAM team
By Lloyd Dunlap
EDINBURGH, Scotland—A group of research-
YORKTOWN HEIGHTS, N.Y.—In the case of amy-
ers in the United Kingdom and the United
States, notable among them University of
Edinburgh Prof. Paul Digard, have located
and described a previously unknown
influenza gene that, while it may not be a
total game changer, sheds an important
light on the dynamics of flu infections.
The results, published in the July 13
issue of Science magazine, prompted Discover magazine to gush that the finding is
“like someone took the text of Macbeth, put
the spaces in different places, and got
Hamlet.” Digard tells ddn that’s a bit of
hyperbole, and it’s probably more accurate
to say that it’s like finding an excellent sonnet hidden in the text of a short play.
As Digard summarizes the process, he
otrophic lateral sclerosis (ALS), why do some
patients—such as renowned baseball player
Lou Gehrig—die quickly, while others—Stephen Hawking comes to mind—survive for
In addition to playing a key role in finding out what
the hidden PA-X flu gene does and where it hides
in the influenza virus, the team at University of
Edinburgh led by Prof. Paul Digard will soon be
publishing the findings of another previously
unknown flu gene.
and other researchers discovered a new
gene in the influenza virus that helps the
virus control the body’s response to
infection and, while this control is exerted by the virus itself, the surprising part
flu continued on page 22
many years? This is one of the questions that
Dialogue for Reverse Engineering Assessment and Methods (DREAM) Project leader
and founder Gustavo Stolovitzky hopes can
be answered in the coming weeks by “the
wisdom of crowds.”
Established in 2006 by the IBM Computational Biology Center and the MAGNet
National Center for Biomedical Computing at
Columbia University, DREAM’s main objective is “to catalyze the interaction between
experiment and theory in the area of cellular
dream continued on page 14
THE STEM CELLS ISSUE, PART 2
Regenerating interest in stem cell medicine
In the second part of our two-part series on
trends in stem-cell research, we examine the
potential of stem cell technologies to assist
in the replacement of organs and tissues, or
possibly even ‘cure’ some diseases.
special report
By Jeffrey Bouley
PHOTO BY Philip Allfrey
Researchers working on both
sides of the Atlantic describe
new influenza gene hidden
among the known ones
Seventh-annual Dialogue for
Reverse Engineering Assessment
and Methods (DREAM) challenge
seeks informatics solutions to
support translational medicine
SEE PAGE 32
PLUS:
GUEST COMMENTARY
FACTS & FIGURES
Dr. Andrew Pecora, chief medical officer
and director of NeoStem Inc., remarks on
the potential for adult stem cell therapies
to manage and treat chronic illnesses
Frost & Sullivan report examines
promise, adoption challenges for stem
cell research tools in Europe
The promise of cell
therapies in treating
chronic diseases
SEE PAGE 11
Report calls Europe’s stem
cell research tools market
‘a hype and a hope’
SEE PAGE 38
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FINaNCe
auguSt 2012 • Drug Discovery News
3
Florida life-science funding bests national rate
TALLAHASSEE, Fla.—In the wake of
waning funding in many sectors of
industry, including recent drops in
biotech capital, Florida has been
seeing dramatic increases in venture capital funding for biotechnology over the past few years. A
report from BioFlorida, a statewide trade association for the bioscience industry, noted that the
growth of new companies in Flor-
ida outpaced the national rate. In
addition, biotechnology venture
capital funding tripled between
2010 and 2011. The report also
noted that the number of biotech
companies in Florida has increased
42 percent to 193 over five years,
while the national growth rate has
been less than 5 percent over the
same period.
Venture funding for the state’s
life-sciences companies has fluctuated markedly over the past four
years, though it seems to be holding
in its current upward trend. The
state reported venture funding of
$69.8 million in 2008, $42.74 million
in 2009, $29.25 million in 2010 and
$86.72 million in 2011. The jump
from 2010’s level of funding to that
of 2011 represents a 207 percent
increase, and from all signs so far,
the Florida life-science industry is
set to beat the $86.72 million seen
last year. In the first quarter of 2012,
$39 million has been raised so far, a
65 percent increase from the fourth
quarter of 2011.
The report highlights Florida’s
dedication to building a life-science
hub, given that it is now home to
institutes such as the Scripps
Research Institute, Sanford-Burn-
ham Medical Research Institute,
Max Planck Florida Institute and
the Torrey Pines Institute for
Molecular Studies.
On the nationwide scale, venture
funding for life sciences was up 21
percent in 2011, but dropped 22 percent for the first quarter of 2012,
according to recent data from the
National Venture Capital Association. ddn
Accelr8
closes
$35
million
investment
DENVER—Accelr8
Technology Corp. has announced
that, having secured shareholder approval and having
met all closing conditions,
the company has finalized a
transaction for an investment of up to $35 million in
its common stock.
Ja c k S c h u l e r, Jo h n
Patience and Lawrence Mehren led the investment group,
and in conjunction with the
closing of the transaction, all
three were appointed to
Accelr8’s board of directors.
In addition, Mehren has also
been named the new CEO.
“We are very pleased with
the investment,” Mehren
said in a press release. “Our
strengthened balance sheet
provides us with the resources needed to realize the significant potential of the company’s unique technology.”
The investment is intended to support final product
development of and bring to
market Accelr8’s BACcel
culture-free diagnostic system for same-shift identification and antibiotic-resistance testing of bacterial and
fungal pathogens. The system is based on Accelr8’s
assay processing and detection technologies, and offers
medical providers the ability
to perform high-risk pathogen detection and major
resistance classification
within hours rather than the
usual two to three days currently required. The company notes that “superbugs”
with high drug resistance
continue to pose a serious
problem in hospitals, causing almost 100,000 deaths
annually in the United
States, according to the Centers for Disease Control and
Prevention. ddn
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markets
4 Drug Discovery News • August 2012
Pharmaceutical and biotech market indices
T
he Burrill Select Index saw a 24.8 percent gain
Burrill Mid-Cap Biotech and Small-Cap Biotech
1974
974
through the first half of 2012, widely outperforming
all other related indices; the Dow Jones Industrial
Average posted a 5.4 percent gain, the S&P 500
posted an 8.3 percent gain and the Nasdaq
Composite Index was up 12.7 percent. Of the companies holding
IPOs, biopharmaceutical company Tesaro successfully completed
a $71 million IPO, selling 6 million shares at $13.50 per share,
which fell in the middle of its expected range. Life-science IPOs
in 2012 are posting on average a 22.7 percent gain from their
IPO prices, with six of the nine companies in positive territory.
Source: Burrill & Co.
Amex Pharmaceutical Index
Burrill Select
306.68 306.14
315.13
318.11
400
338.09
325.22 330.68 332.25
337.8
331.61
335.76
351.48
2000
75
75
1752
1800
1600
1406
1391
1386
1277
1284
1248
1096
6
1136
1140
1111
1034
1076
1009
1065
1135
35
1200
1000
1034
824.55
829.11
1400
8
893.95
911.12
9
941.62
800
793.9
0
1346
1338
1325
1404
1389
1444
1400
1265
350
1079
1141
1126
1138
1200
1120
300
1000
250
800
200
600
150
400
100
200
50
0
0
Source: Burrill & Co.
Source: Yahoo Finance
June bustles with regulatory, judicial activity
By Burrill & Co.
SAN FRANCISCO—Regulatory
news largely
dominated the industry in June, Burrill & Co.
noted in its latest report, as the U.S. Supreme
Court ruled to uphold the individual mandate
of the Affordable Care Act, the Obama
Administration’s landmark, contentious
healthcare reform legislation. The decision
was passed down in a 5-to-4 ruling, written
by Chief Justice John Roberts, who noted that
although the individual mandate did not
count as a valid exercise of Congressional
power under the commerce clause, the mandate was appropriate as a tax. He was joined
by Justices Stephen Breyer, Elena Kagan,
Ruth Bader Ginsburg and Sonia Sotomayor
in the majority, the latter four of whom added
that they believed the mandate to be constitutional under the commerce clause as well.
“Although it will take some time to determine the full impact of the ruling, meaningful
reform has already been set into motion,
driven by payers, physicians, patients and
technology,” says G. Steven Burrill, CEO of
Burrill & Co. “The pace of that reform will
only accelerate as cost pressures drive governments, insurers and healthcare systems
to seek new ways to deliver better value and
access to patients for less money.”
While Burrill notes that there is a great
deal to process regarding the decision,
“investors don’t like uncertainty,” and as
such, the attainment of a determination
regarding the issue “will allow healthcare
reform to move forward and remove doubt
for life-sciences companies.”
The decision also means a pathway for
biosimilars, which was included in the law, will
continue to be implemented. In other regulatory news, the president is expected to sign
legislation for the renewal of the Prescription
Drug User Fee Act, which allows the U.S. Food
and Drug Administration (FDA) to collect fees
from the industry to fund its review of products
submitted for marketing approval. The legislation is intended to improve drug review transparency, speed drug review and extend for five
years the fees that drug and medical device
companies pay to support FDA employees that
P
u
b
l
i
c
months of 2012 compared to the same period
in 2011. Partnering also waned, though Inhibrx
announced a worldwide option and licensing
agreement with Celgene to the tune of $500
million for an undisclosed antibody program.
Global partnering activity was also down,
dropping more than 24 percent to $15.1 billion.
Notably, the FDA approved Belviq, the first
new obesity drug in 13 years, giving Arena
Pharmaceuticals, the creator, a firm foothold
in a market that represent a growing health
concern. ddn
review the products. In keeping with the growing attention paid to biosimilars, the bill also
includes new fees to be paid by companies creating generic drugs and biosimilars.
M&A activity continued to be fairly lackluster, with the largest deal consisting of BristolMyers Squibb agreeing to acquire Amylin
Pharmaceuticals for $5.3 billion, a more successful endeavor than the original $3.5 billion
bid offered in March. On the whole, global
M&A activity was down to $65.9 billion, a
more than 41 percent decrease in the first six
C
o
m
Profit, net sales up marginally for Sanofi
PARIS—Sanofi
saw a profit of $3.2 billion in the first quarter of 2012, a
12.5-percent increase over the same quarter last year. Total sales for the quarter reached approximately $11.2 billion, an increase of 9.4 percent over the
first quarter of 2011, including Genzyme consolidated sales of $1 billion. Gross
profit rose 8.5 percent to $7.6 billion, and research and development expenses were also up, rising 6.9 percent to $1.5 billion. Net sales were up 15.2
percent in the United States for the quarter, down 1.5 percent in Western Europe
and up 9.9 percent in emerging markets such as Eastern Europe, Turkey, Asia,
Latin America, Africa and the Middle East. Revenue from Sanofi’s new Genzyme
unit was $529.7 million for the quarter, an increase of nearly 14 percent. The
company says its Q1 performance is in line with the guidance it released for the
full year, adding that “2012 business EPS is expected to be 12 percent to 15
percent lower at CER than 2011.”
PerkinElmer increases 2012 guidance
WALTHAM, Mass.—PerkinElmer Inc. posted net income of $22.6 million, or
20 cents per share, for the first quarter of 2012, down from $24.9 million,
or 22 cents per share, in the same period of last year. Earnings for the quarter on a non-GAAP adjusted basis were up 23 percent at 43 cents per share,
beating both the 35 cents per share reported in Q1 of 2011 and analysts’
p a
n
y
N
e
w
s
estimates of 41 cents per share for this quarter. Revenue was up 14 percent
to $510.9 million from the $447.2 posted last year, nearly matching the
$510.4 million that analysts had expected. Operating income from continuing operations decreased, falling from $41.4 million in Q1 of 2011 to $36.4
million for this past quarter. Operating cash flow from continuing operations
was $15.3 million, down significantly from the $47.3 million the company
reported in the year-ago period.
Nanosphere’s stock surges in Q2
NORTHBROOK, Ill.—Nanosphere released preliminary results for the second
quarter of 2012 recently, reporting revenues of $1.3 million, up from the $0.5
million reported in the same quarter of 2011. The company’s cash and equivalents as of June 30 were $23.7 million, compared to the $39.3 million
reported as of Dec. 31, 2011. The company’s stock saw a large jump lately—
topping its 52-week high before July 4—on news that global securities and
investment banking group Jeffries lifted its rating on Nanosphere stock from
“hold” to “buy.” The attention is based on recent news from the company
regarding the recent de-novo appeal Nanosphere received from the U.S. Food
and Drug Administration, which approved marketing of the company’s GramPositive Blood Culture Nucleic Acid Test (BC-GP) on the automated sampleto-result Verigene System.
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b r i e f s
University of Cambridge
in R&D pact with GSK
CAMBRIDGE, United Kingdom—The
University
of Cambridge has announced the initiation of a
program of scientific open collaboration with
GlaxoSmithKline PLC (GSK). Teams of Cambridge scientists will work with GSK and other
organizations to advance drug discovery and
development. Cambridge Enterprise, the commercialization arm of the University of Cambridge, will facilitate the program. Researchers
involved with the program will be based at Stevenage Bioscience Catalyst, which is located at
GSK’s research and development center.
“This open innovation approach is enabling
scientists who might not ordinarily have interacted
to build relationships, share ideas and seek advice.
This environment provides us with an opportunity
to stimulate research and translate science into
the discovery of new medicines for patients,”
Patrick Vallance, president of Pharmaceuticals
R&D at GSK, said in a press release.
Daiichi Sankyo,
Ranbaxy look to Venezuela
Sankyo Co. Ltd. and Ranbaxy
Laboratories Ltd. have announced the launch of
a hybrid business model in Venezuela. Daiichi
Sankyo Venezuela SA, a subsidiary of Daiichi
Sankyo, will begin marketing Ranbaxy products
in Venezuela as part of the business model.
Ranbaxy has been marketing its products in
Venezuela through a local distributor, but Daiichi
Sankyo Venezuela will assume that role in its
stead and has already begun promotion of Ranbaxy products. Daiichi Sankyo initiated its presence in Venezuela—which boasts the third-largest pharmaceutical market in Latin America—
with pharmaceuticals such as Benicar, its
hypertension medicine. The company now plans
to expand Ranbaxy’s product portfolio to promote the hybrid business model.
Of warheads and wellness
Cancer Research
Technology and ADC
Therapeutics join
forces on antibodydrug conjugates
By Jeffrey Bouley
LONDON—Cancer Research Technology (CRT), the commercial
arm of Cancer Research UK, and
recent startup ADC Therapeutics Sarl (ADCT) in Lausanne,
Switzerland, in early July signed
agreements to develop antibodydrug conjugates (ADCs) using
CRT antibodies and peptides,
and ADCT’s “warhead” and
linker chemistries, to fight
cancer.
The warheads coming out of
ADCT—which was recently
established with $50 million
from Celtic Therapeutics, a private equity firm, to develop a
pipeline of as many as 10 new
Cancer Research UK is a key part of the deal between Cancer Research Technology
(CRT) and ADC Therapeutics (ADCT), not just because it is the parent organization
of CRT, but also because it originally funded some of the technology that helped
establish Spirogen, the creator of the PBD technology ADCT is using.
therapies based on ADCs—are
based on proprietary technology
around pyrrolobenzodiazepines
(PBDs) that was developed by
London-based Spirogen Ltd. It
was in March of this year that
ADCT and Spirogen announced
a partnership to develop proprietary ADC products, and that
connection to Spirogen provides
a dual link for ADCT to CRT and
Celtic, as some of the technology
that went into Spirogen’s formation was originally financed by
Cancer Research UK academic
funding, and Celtic is a major
investor in Spirogen, notes Laura
Fletcher, associate director of
business management at CRT.
“Over the years we’ve had all
kinds of dialogue with Spirogen,
and a couple years ago, we started looking at whether CRT had
access to targeting agents that
might fit well with their ADC
technology,” Fletcher tells ddn.
“With the founding of ADC
Therapeutics, those discussions
pretty much transferred over to
them, but much of the management team is shared between
ADCT and Spirogen, so there’s
significant overlap and continuity. Many aspects of the current
agreement are extensions of
deals we formed a year ago or
more with Spirogen to work on
promising targeting agents and
the current agreements are to
take the work into the in-vivo
realm.”
ADCT will initially fund preclinical studies for the new ADCs
in a range of cancer models, but
other deal terms were not disadc continued on page 7
TOKYO—Daiichi
Biogen Idec, Isis
partner on antisense drug
WESTON, Mass.—An exclusive, worldwide option
and collaboration agreement has been established between Biogen Idec and Isis Pharmaceuticals Inc., under which the companies will
develop and commercialize a novel antisense
drug to treat myotonic dystrophy type 1, also
known as Steinert disease. Biogen Idec will pay
Isis $12 million upfront, and has the option to
license the drug from Isis up through the end of
the Phase II trial. Isis stands to receive up to $59
million in milestone payments associated with
clinical development, up to an additional $200
million in a license fee and regulatory milestone
payments and double-digit royalties on sales of
the drug. Isis is responsible for global development through the completion of Phase II clinical
trials, and if Biogen Idec exercises its option, it
will assume responsibility for global development, regulatory and commercialization duties.
An acquisition
with some heart
Janssen-Cilag acquires CorImmun,
gains heart failure drug
“We believe that new medicines and new combination therapies to treat TB will be
delivered through a concerted effort from multiple partners, rather than one company’s
lab,” said Dr. Manos Perros, head of AstraZeneca’s Infection Innovative Medicines unit.
With approximately $925,000
in funding from the Wellcome
Trust, AstraZeneca and Cellworks will collaborate on the
design of novel combination therapies to treat multi-drug resistant
tuberculosis (MDR-TB).
“AstraZeneca is pleased to join
this effort to speed the delivery of
improved treatment combinations
for TB patients worldwide. Our
continued investment in infectious
disease research has positioned us
to collaborate with organizations
like Cellworks that share our pas-
NEUSS, Germany—Janssen-Cilag GmbH has announced the completion of its acquisition of privately held CorImmun GmbH, a
drug development company based in Germany. No financial
details were disclosed, other than that the purchase was made
for an undisclosed upfront payment as well as a contingent
future clinical milestone payment.
CorImmun was founded in 2006, a spinoff from the University
of Würzburg and University of Tübingen. Located in Martinsried
near Munich, the company focuses primarily on therapeutics and
diagnostics for heart and vascular diseases, and works with all
steps of the process from research to commercialization. The company’s lead compound, COR-1, is a small cyclic peptide, currently
in the early stages of development for the treatment of chronic
congestive heart failure. In preclinical studies, the compound has
been shown to improve heart function by decreasing autoimmune,
beta 1 receptor-simulating antibody effects. CorImmun initiated
a clinical Phase II trial of the compound in September of last year.
Per the terms of the agreement, Janssen and its affiliates will
take over full development and global commercialization responsibilities for COR-1 immediately. No details were released as to
the company’s plans for CorImmun’s facilities or employees following the acquisition, and as of press time, Janssen did not
respond to inquiries for additional information.
“The prevalence of heart failure is rising rapidly, and COR-1
is an early-stage development compound with a novel mechanism
tb continued on page 9
heart continued on page 9
Tackling the
TB epidemic
AstraZeneca, Cellworks
and Wellcome Trust
team up to fight drugresistant tuberculosis
By Amy Swinderman
LONDON—As tuberculosis drug
sensitivity and resistance reaches
epidemic proportions in many
parts of the world, three organizations have teamed up to tackle
this crisis: global pharma AstraZeneca PLC, Indian biopharmaceutical firm Cellworks Inc. and
England’s Wellcome Trust.
By Kelsey Kaustinen
adc
continued from page 6
closed, nor are the cancer targets a
matter of public discussion yet.
However, Fletcher did share that,
“The agents we are looking at are
against targets that have not yet
been tested in the ADC arena,
which fits well with CRT’s goal to
fill gaps and explore areas that others haven’t—that makes this deal fit
the box very well for us.”
ADCs are a clinically important
class of oncology drugs because
they combine the specificity of antibodies with novel warhead chemistries, note ADCT and CRT. The
antibody component selectively
targets the cancer cells to deliver
tumor-destroying chemicals that
are internalized into the cancer cell
while avoiding damage to healthy
tissue. Once inside the cancer cell,
the linker degrades and the active
toxin is released, binding to the
cell’s DNA and killing the cancer
cell. ADCT’s toxic chemicals interact with DNA without disrupting
the double helix structure, which
avoids triggering DNA repair processes. In part, it is hoped that this
will prevent drug resistance.
“ADCs are receiving a lot of
attention at the moment, in part
because Seattle Genetics got an
ADC product approved recently,
plus there’s another product
[Roche’s Trastuzumab-DM1]
showing promise in clinical studies,” Fletcher explains. “There is a
lot of attention on the potential for
ADCs to strike a therapeutic blow
and take toxins straight to the
source to eliminate tumors. It’s a
field that has generated great
excitement, so it’s a great time to be
involved in this area.”
“We are very excited to see our
potent PBD-based warheads combined with CRT’s leading tumortargeting antibodies and peptides,”
said Dr. Chris Martin, ADCT’s collaboration manager and CEO of
Spirogen, echoing Fletcher ’s
upbeat attitude in the news release
about the deal. “Together, we are
committed to faster and more efficient drug development, and have
already commenced our preclinical
work for these exciting programs.
We believe this provides a very
promising and rapid route to
develop novel ADCs for cancer
therapy and are very much looking
forward to working in partnership
with CRT.”
C a l l i n g t h e c o l l ab o r at i o n
“unique,” Dr. Phil L’Huillier, CRT’s
director of business management,
said in the same news release that
the collaboration “marries ADCT’s
targeted portfolio with CRT’s
access to world-class cancer
research supported by GBP 334
million each year. We hope the collaboration will identify a range of
ADCs that can be taken forward
for development into innovative
new ways to treat cancer and save
lives.” ddn
global news
August 2012 • Drug Discovery News 7
Cancer Research
Technology and
BioInvent team up
LONDON—Cancer Research Technology Ltd. (CRT)
also announced last month that it has entered into
a collaboration with BioInvent International AB and
Queen Mary, University of London, to identify new
therapeutic antibodies in oncology.
BioInvent and scientists funded by Cancer
Research UK at Queen Mary, under the leadership of
Dr. Thorsten Hagemann, Senior Cancer Research UK
Fellow, will search for new therapeutic targets by
applying BioInvent’s F.I.R.S.T. technology, a functional approach to therapeutic antibody discovery.
Hagemann and his team will provide biological pathways for the development of new oncology therapies.
The F.I.R.S.T. platform, through its biopanning technology, enables identification of functionally superior
antibodies across multiple targets overexpressed by
target cells. This combined target and drug discovery
platform utilizes primary cancer patient cells, rather
than recombinant proteins, as an antigen source
allowing for discovery of novel specificities (receptors
and epitopes) and target receptor functions.
The agreement gives BioInvent the option to enter
into licenses to bring forward drug candidates beyond
lead candidate identification in exchange for milestones and royalties to CRT.
“By combining the preclinical expertise in animal
models within my laboratory and our access to
patient samples with BioInvent’s F.I.R.S.T. technology,
we hope to speed up the discovery and development
of new possible treatments,” said Hagemann in a
news release announcing the partnership. “We will
focus primarily on targets which affect the pro-tumor
role of myeloid cells in solid malignancies, an area
in which my lab has developed significant experience.
We would anticipate such therapies to be applicable
across a range of tumor types.” ddn
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global news
MCPs for COPD and asthma
Prosonix and the Imperial
College London partner on
engineered multi-component
particles for respiratory
medicines
By Lloyd Dunlap
OXFORD, U.K.—Prosonix has signed a collaborative research agreement with Imperial College
London to accelerate the development of its
engineered multi-component particles (MCPs)
as respiratory medicines, per an announcement made by the partners last month.
The collaboration will result in Prosonix
working closely with Dr. Omar Usmani, an
expert in respiratory diseases and inhaled
drug delivery at the college’s National Heart
and Lung Institute (NHLI). The work aims to
develop a deeper understanding of how MCPs
key performance criteria, including synergistic effects in reducing inflammation and
improving bronchodilation resulting from
co-localization of active drug components
with other combination formulations including marketed combination products.
Prosonix’s drug-particle engineering
approach and expertise has enabled the
development of MCPs that combine two
active respiratory drug molecules consistently in a pre-determined ratio in each particle in the formulation, without the need for
additional excipients.
“We use ultrasound to control nucleation,
which is the first step in crystallization,” says
Prosonix CEO David Hipkiss.
Traditionally, formulators were taught to
make big crystals—on the order of 50 to 200
micron—then crush them. This provides
effective size control, but introduces entropy,
“We believe that our particle engineering technology
is potentially transformational in enabling the
development of novel inhaled combination therapies
that deliver significant clinical benefits.”
David Hipkiss, CEO of Prosonix
can be translated into new respiratory medicines with significant clinical benefits compared to existing combination formulations
in chronic obstructive pulmonary disease
(COPD) and asthma. A “rapid synergistic
potentiation” has previously been reported
for the simultaneous administration of corticosteroids and beta-2 agonists.
Results from the collaboration are intended
to accelerate the development of Prosonix’s
PSX2000 MCP Series of novel combination
medicines, with the aim of advancing one or
more MCP candidates into formal preclinical/
proof-of-concept studies in 2013. The collaboration will investigate MCPs in in-vitro and
in-vivo models of the lung. It will also compare
Hipkiss notes.
“We use ultrasound to get controlled nucleation and crystal growth from solution without any further application of energy. As a
result, we are able to put a fixed-dose combination —with no fancy excipient—into a pressurized metered dose inhaler (pMDI) formulation that is uniform within each dose, and
from dose to dose using simple, multidose
delivery devices,” he says.
Excipient-free, drug-only MCPs engineered by Prosonix that will be evaluated in
the project include inhaled corticosteroids
with long-acting beta-agonist (LABA) and
LABAs with long-acting muscarinic antagonists, Hipkiss says.
Register Early and SAVE!
10
“Our strong links with the world’s leading
academic research groups focused on respiratory medicine and inhaled drug delivery, such
as Dr. Omar Usmani’s group at Imperial College’s NHLI and Prof. Rob Price’s team at the
University of Bath, alongside our own development team, will ensure that Prosonix
retains a preeminent position in the field. We
believe that our particle engineering technology is potentially transformational in enabling
the development of novel inhaled combination
therapies that deliver significant clinical benefits. Following the recent close of our $20.6
million financing, we believe we are very well
placed now to drive the development of our
unique MCPs into the clinic,” he adds.
Usmani adds, “Co-localization of active
components in respiratory drug combinations in the lung may offer the potential for
an enhanced clinical effect and therapeutic
efficacy that is currently not fully achieved
with current combinations. We are extremely
interested in Prosonix’s particle engineering
approach and MCPs to determine whether
they can demonstrate clinical synergy and
thus provide a novel and effective means of
delivering respiratory combinations.”
Prosonix is not a “vapor-ware” company,
Hipkiss points out. Changes in its business
model over the past 18 months have moved it
from the “service world” to a processing mode
in the respiratory space, he notes, with processes in place and at work. Its current development programs include PSX1001, a drugonly directly substitutable generic version of
fluticasone propionate, a potent inhaled corticosteroid monotherapy for asthma in
metered dose inhaler (pMDI); PSX1002, a
drug-only version of glycopyrrolate, a longacting muscarinic antagonist for chronic
obstructive pulmonary disease in pMDI; and
PSX2000 MCP Series, a potentially revolutionary approach to combination therapy for
respiratory diseases using MCPs. ddn
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Annual
October 1-3, 2012
Boston Marriott Copley Place
Boston, MA
The Leading Event on Novel Drug Targets
EVEnt HigHligHtS
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100+ Distinguished Faculty
Organized by
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SciEntific PrOgrAmS
October 1-2
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GPCR
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PI3K Pathway
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Functional Genomics
Histone
Deacteylases
Histone Methyltransferases
and Demethylases
Cancer Cell Metabolism
Diabetes
DiscoveryOnTarget.com
valeant
focused on the healthcare industry.
An additional $114 million in potential
contingent payments is also possible
if certain milestones and revenue
targets are reached. The transaction
was expected to close in June, and
is expected to be accretive to Valeant
in 2012.
The acquisition is one of several
transactions Valeant has completed so
far in 2012. Valeant acquired Pedinol
in April for less than 1.5 times sales.
Pedinol, a privately owned specialty
pharmaceutical company that focuses
on podiatry, posted revenue of approximately $18 million in 2011, and the
acquisition was expected to be immediately accretive. Valeant also acquired
Natur Produkt International JSC for
roughly $180 million (with the potential for an additional $5 million in milestones), which gained it a large presence in the over-the-counter segment
in several categories and enhanced the
company’s presence in Russia. Eyetech
Inc. was acquired in February for less
than two times sales, and Probiotica
Laboratorios Ltd. was acquired in the
same month for approximately $74.1
million). Both acquisitions were
expected to be immediately accretive.
OraPharma develops and commercializes products for the improvement
and maintenance of oral health for
dental practitioners and patient care.
Founded in 1996, the company became
a subsidiary of Johnson & Johnson in
2002, and then was acquired by Water
Street Healthcare Partners in 2010.
“We are excited to enter a new
attractive market segment with an
already established sales infrastructure focused entirely on the dental
community,” J. Michael Pearson,
chairman and CEO of Valeant, said in
a press release regarding the deal. “We
believe that this market segment has
similar characteristics to the dermatology, podiatry and ophthalmology markets and should offer us the opportunity to cross-sell some of our current
products, most notably our new topical prescription cold sore medication,
Xerese. We believe the OraPharma
business is a new growth platform
from which to build additional opportunities in the future.”
OraPharma’s leading product is
Arestin, a locally administered antibiotic that is indicated as an adjunct to
scaling and root planing procedures to
reduce pocket depth in patients with
adult periodontitis. OraPharma partners with Johnson & Johnson Healthcare Products to offer Listerine and
Reach products, and partners with
DePuy Spine Inc. to offer HEALOS
Dental Bone Graft Substitute, which is
“intended to fill, augment or reconstruct periodontal and/or bony defects
of the upper or lower jaw.”
No details were released as to
Valeant’s plans for OraPharma’s
employees or its facilities in Horsham, Pa., and neither company
responded to requests for comments
on the transaction. ddn
global news
tb
sion for medical innovation. AstraZeneca would like to acknowledge
and thank the Wellcome Trust for
funding this important work. We
believe that new medicines and new
combination therapies to treat TB
will be delivered through a concerted
effort from multiple partners, rather
than one company’s lab,” said Dr.
Manos Perros, head of AstraZeneca’s
Infection Innovative Medicines unit,
in a statement.
Tuberculosis affects approximately one-third of the world’s
population, according to the World
Health Organization. MDR-TB has
become a serious public health concern in many countries, as its treatment is longer and requires more
expensive drugs. People with MDRTB are usually treated with at least
four effective antibiotics over a typical course of 18 to 24 months.
AstraZeneca and Cellworks
intend to tackle this difficult issue by
employing Cellworks’ proprietary
predictive platform to model MDR-
TB and “rationally identify synergistic combinations that might have the
highest efficacy and lowest possible
toxic burden compared to all currently available combinations,” says
Anand Anandkumar, managing
director of Cellworks Group India.
The two companies previously
used this platform to develop a virtual predictive model for the bacterium E.coli.
“Thus, we have already had a
successful collaboration model
where Cellworks does the in-silico
work, and AZ India does the experi-
mental validation,” says Anandkumar. “AZ India is the only one within the big pharma companies that
have a dedicated program in the
anti-tubercular drug discovery
space in India. They have a state-ofthe-art biosafety lab that allows
them to do all the experiments
required for preclinical drug discovery in the TB space.”
Cellworks will create predictive
dynamic maps of MDR-TB and use
its proprietary simulation and analysis techniques to emulate drug
resistance, search tens of thousands
of combination quartets from an
existing pool of anti-infective drugs
and identify top-performing drug
combinations that work against
MDR-TB. AZ India will do the invitro testing, followed by validation
using in-vivo models.
“Upon successfully completing
this project, Cellworks and AZ will
seek additional funding from various channels including the Wellcome Trust to allow taking the
MDR combination to human trials,”
says Anandkumar. ddn
heart
for treating heart failure that
has the potential to improve
heart function by suppressing
antibodies that can exacerbate
this condition,” Dr. Peter M.
DiBattiste, global therapeutic
area head for cardiovascular
disease and metabolism at Janssen Research & Development,
said in a press release regarding
the deal. “This acquisition demonstrates Janssen’s commitment to investing in innovative
science in an area of great
unmet medical need, where
new therapies can improve the
quality of patient care.”
Heart failure is a progressive
disease characterized by the
inability of the heart muscle to
adequately pump enough oxygenated blood throughout the
body, and it is estimated that 23
million people worldwide have
been diagnosed with the disease. According to the National
Heart, Lung and Blood Institute
of the U.S. National Institutes of
Health, roughly 5 million people
in the United States have heart
failure. A 2010 report from the
American Heart Association
Statistics Committee and Stroke
Statistics Subcommittee noted
that about 670,000 people are
diagnosed with heart failure
each year, and approximately
one in five die within one year
of diagnosis. There is no cure
for most causes of heart failure,
and the leading causes consist
of diabetes, high blood pressure
and coronary artery disease.
The Centers for Disease Control
and Prevention rank heart disease as the leading cause of
death annually in the United
States.
Another acquisition was
completed just two weeks prior
by Janssen’s parent company,
Johnson & Johnson. The pharmaceutical giant announced
the completion of its acquisition of Synthes Inc. for $19.7
billion in cash and stock. As a
result of the transaction, Synthes will be integrated into the
DePuy franchise, leading to the
establishment of the DePuy
Synthes Companies of Johnson
& Johnson. ddn
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editorial
Public misconceptions about stem cells
throw a wrinkle into scientific progress
R
employ stem cells to erase wrinkles, reduce redness, fade age spots and lift sagging skin. They
etrist for my yearly eye exam seem to rely on the public’s misconception that
and to obtain new eyeglasses stem cells are Mother Nature’s miracle, with the
and contact lenses. When the power to do everything from eradicate disease to
give people a surgery-free facelift.
good doctor came to
These messages are aimed at the same
fetch me from the
people who believe “media reports”
waiting room, he said, “come on
that Pepsi is using “aborted baby
back, young lady,” but glancing from
cells” in drink research.
me to the information listed on my
Those of us who are a bit more
chart, he quipped, “ooh, you’re no
informed about the science and
young lady.” (I come from a long line
potential of stem cells, however, are
of Southern women who taught me
able to sort fact from fiction. Skincare
how to grind my teeth and kill such
companies are not using human
socially inept creatures with kindembryonic stem cells; the last time I
ness.) A few weeks later, I elected to Amy Swinderman,
ddn Chief Editor
checked, the U.S. Food and Drug
take a telephone survey about political candidates, and when the survey reached Administration hadn’t approved any process by
the demographic portion of the inquiry, I wait- which live materials are somehow incorporated
ed, rather impatiently, for my age group to be into consumer-grade dermatology products. At
announced. When did I get so far down the list? best, these companies are creating products with
As I creep ever nearer to my 40s, I’m assessing plant stem cells, specialized peptides or enzymes
the options available to me that will somehow that reportedly help protect human skin stem
preserve the fountain of youth—because as the cells from damage and deterioration, or perhaps
great Dolly Parton warned in the popular 1990s stimulate the skin’s own stem cells.
The great divide between actual science and
film “Steel Magnolias,” “Time marches on, and
sooner or later, you realize it is marchin’ across general public perception—complicated by
your face.” I’m educated enough to know that no political controversy and ethical debate—has
lotion or potion is going to rewind my physical only grown deeper with every breakthrough or
clock, but if there is anything I can do to protect achievement in the quest to use stem cells to
regenerate or repair damaged tissue, skin and
and preserve, there’s no harm in that, right?
Well, it looks like a bevy of rather creative skin- organs. Worse yet, such controversies have sigcare manufacturers seem to think so. A quick nificantly slowed scientific and commercial
look around the “anti-aging” skin-care market progress, as noted by our features editor, Ranyields dozens of creams, serums, masks and other dall C. Willis, in the second part of our series on
products that claim to turn back the hands of trends in stem cell research, “Regenerating
time—via the use of stem cells. The marketing interest in stem cell medicine,” a feature report
tactics employed by the “laboratories” responsi- that begins on page 32.
“When the idea of embryonic stem cells first
ble for these dermatological wonders are deliberately vague in describing how the products came up about three decades ago, conversations
By Amy Swinderman
ecently, I visited the optom-
The great divide between actual
science and general public
perception—complicated by
political controversy and ethical
debate—has only grown deeper
with every breakthrough or
achievement in the quest to use
stem cells to regenerate or repair
damaged tissue, skin and organs.
www.drugdiscoverynews.com
ran rampant about the potential—pluripotential,
if you will—of this technology to cure all human
disease and assist us with replacement organs
and tissues as those in our aging bodies failed
over time. Despite a few early achievements,
however, the hype quickly trailed off to be
replaced by disappointment and anxiety,” Willis
writes. However, he also notes, “While not necessarily abandoning the desire to outright replace
damaged tissues—and perhaps, one day, organs
via tissue engineering—stem cell companies have
tamped down earlier rhetoric on being ‘the’ solution for human disease.”
That’ll be the first step in normalizing public
expectations for stem cell therapies. Then, conversations between companies, regulators and
payors must begin, with those of us entrusted
with reporting on these developments doing so
in a more responsible and approachable way.
Here’s hoping that the scientific community
uses the growing “stem cell skin care” market as
an opportunity to educate the general public
about the actual science and promise of stem
cells. Until then, I guess I’ll just slather on some
sunblock and embrace the next phase of my life,
wrinkles and all. ddn
Lloyd Dunlap, Lori Lesko, Jim Cirigliano,
Ilene Schneider, Chuck Green
August is back-to-school month
M
By Peter T. Kissinger and Candice Kissinger
uch has been written about fail-
ing schools and our student performance ranking below other
nations on standardized tests for
science, technology, engineering
and mathematics (STEM) subjects. We are
unconvinced that Finland, with its population
smaller than many American cities and less
diverse than a bag of frozen peas, is a reasonable
benchmark. Many gurus respond that science
teachers should have deeper content knowledge
and science as their primary college major. That’s
STEM advances one kid
at a time, and it only
takes one to make a
difference in this world.
a noble thought, but the disincentives are many.
We’ve followed the science education debate for
years, but jumping into the fray has caused us to
think in new ways.
One fallacy of stressing science content
knowledge is the fact that it’s not often a real
problem. The stressors on our system derive
mostly from a society that values entertainment
over learning. Ours is a time where many fami-
lies are badly broken, and children are having sure be a different sport if only aggregated batting
children in a cycle of poverty and despair. Tech- averages were reported.
It’s odd that academic competition among stunology has advanced so rapidly and been disdents is discouraged in school when
seminated so broadly that it is hard
it is the key to nearly every other
to be excited by improvements we
activity in life. Competition is said by
make today.
some to make schools as a whole betVilifying teachers fits the idea,
ter, but why not students? When we
accepted by many, that everything
were in school, it made students betuntoward that happens is someone
ter. Experiencing disappointment
else’s fault. Educators are a conveand failure made those inevitable
nient scapegoat, but not the only one.
experiences easier to handle later,
When seeking candidates for a STEM
and inspired us to try harder. The
teaching job, it is illegal to ask for a
majority of great figures from history
birthday, but it is acceptable to ask
Peter T. Kissinger,
improved in the same way.
when the candidate graduated from Purdue University
University professors are recruithigh school. If that date is prior to
1990, many transitioning scientists will run into ed from school to school. They are incentivized
to stay or depart, just like a free-agent point
a barrier called “too old, too experienced.”
Those fortunate to then receive an interview guard. Schoolteachers, on the other hand, lose
in many school districts will find that one of the their salary and benefits (and/or seniority) if
first questions is, “What can you coach?” A sat- they trade one district for another. Imagine if
isfactory answer does not include chemistry, Pfizer and Merck—or Harvard and Yale—exerbiology, math or physics. A beginning science cised this constraint of trade? It strikes us odd
teacher at any age is not going solve our STEM that some want to encourage competition
among schools for students (via parents) using
problem by coaching sports.
We find it curious that some middle-school a voucher system, but don’t likewise encourage
teachers are judged on scores from standardized competition for the best teachers. That is
tests taken by students for whom the grade has no un-American.
It is further curious that some states propose
consequence at all. What is the motivation for students to get a grade that only applies in the aggre- financially rewarding schools where the students
gate to their teacher and school? Baseball would
school continued on page 11
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Editorial
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[email protected]
Features Editor
Randall C. Willis
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editorial
Commentary: The promise of cell
therapies in treating chronic diseases
T
By Dr. Andrew Pecora, Neostem Inc.
he practice of medicine contin-
ues to evolve with advances in science, biology and technology, and
in many cases, their convergence.
We see evidence of these advancements all around us, from the use of monoclonal antibodies to treat autoimmune diseases and cancer to new devices that monitor
a failing heart and shock it back into normal
function.
Healthcare in general is entering a crisis
phase due to the rising cost of treating patients
with chronic diseases. People are living longer with these diseases, and due to medical
breakthroughs, dying less from acute diseases. Regenerative medicine, however, is at
the forefront of a vital, emerging trend in
healthcare. With the introduction of adult
stem cell therapies, we are now seeing new
promise in the management and even treatment of chronic disease.
Countless lives have been saved with the
advent of bone marrow transplantation,
which many people do not realize is actually
a type of stem cell application. Rebooting the
body’s immune system through cell therapies,
as opposed to designing and administering
traditional billion-dollar pharmaceuticals, is
heralding a new era in healthcare and can
have a significant impact on healthcare costs.
Evidence of this transformation is all
around us. We continue to see more developmental-stage, cell-based products in clinical
stop the progression of heart failure by require a bone marrow transplant have a
replacing damaged heart muscle with new hard time finding a healthy match. With
muscle cells.
autologous cells, however, there is less of a
Within the cardiovascular space, we see chance of rejection. Much like there is no one
two major areas of opportunity with adult drug to treat every disease, there is no one
stem cell therapies. Adult stem cells hold the cell type to treat every disease. To that end,
ability to spare cardiac tissue that has sus- the challenge of whether to use allogeneic or
tained an injury from ischautologous stem cells will
emia, but has not yet died.
have to be decided on a caseCardiac tissue is spared
by-case basis.
through the prevention of
The future of stem cell therapoptosis (programmed cell
apies relies in part on the abildeath) and revascularization
ity to educate the public on the
at the cellular level. The prebenefits of these therapies.
vention of apoptosis helps in
When talking about stem cells,
preserving cardiomyocytes
many people still revert back
and their function, allowing
to the previous controversy
them to compensate for nonover the use of embryonic stem
functioning cardiomyocytes.
cells that involve the destrucAdditionally, we have seen
tion of a human embryo. The
a different cell type, cardiac
use of adult stem cells in
progenitor cells (CPC), which Dr. Andrew Pecora, NeoStem Inc. research and therapy, howevhold the potential to actually generate new er, is not considered to be controversial.
cardiomyocytes after cardiac tissue death. Greater public understanding is necessary to
Developments in cell-based therapies, like the drive more interest in the field, both from an
therapies mentioned earlier, can offer hope investment standpoint and from the general
for patients who are in heart failure or have public. Market awareness seems to follow a
chronic myocardial ischemia and for patients direct path from a state of skepticism to a gold
who have had large heart attacks.
rush, and cell therapy is already making its
With this new class of therapy comes a way along that path.
host of challenges, including regulatory,
Once these therapies are proved to be safe
business and biological challenges. Although and effective, adult stem cells will change the
the regulation of drugs and medical devices expected paradigm of chronic or progressive
has long been a function of the FDA, the heart failure along with a host of other
chronic diseases. We expect that this paradigm shift in healthcare will help to control
the rising costs of treating chronic disease,
spanning from cardiovascular disease to
cancer to neurologic disease to autoimmune
disorders. When you consider that the United States already spends more than $200
billion per year managing diabetes alone, it
becomes clear how important the management of these conditions really is, not only
to the health of our country but also to the
future of our economy. We look forward to a
regulation of cellular therapies that employ whole new era of medical innovation with a
cells from within our own bodies is a new world of possibilities. ddn
hurdle. As of late, the topic of FDA regulation when it comes to stem cells has sparked Dr. Andrew Pecora is the chief medical officer
opposing viewpoints. With that being said, and director of Neostem Inc., an international
we have seen great collaboration from regu- biopharmaceutical company with adult stem cell
latory agencies when it comes to cell-based operations in the United States. Pecora served
therapies here in the United States as well as as chairman and CEO of Progenitor Cell Therapy
abroad, and we expect to continue seeing leading up to its merger with Neostem. He was
that collaboration when additional stem cell appointed to NeoStem’s board of directors in
therapies are proved to be safe and effective December 2011. Pecora is also the founder of
in clinical trials.
Amorcyte, a Neostem company pursuing cellAs more trials assessing the therapeutic based therapies for the treatment of cardiovasuses of stem cells are underway and proved cular disease, and its first chairman and CEO.
successful, we will start to see these therapies Additionally, Pecora serves as vice president of
being delivered to the market in a cost-effi- cancer services and chief innovations officer at
cient way through the management of distri- the John Theurer Cancer Center at Hackensack
bution, sales and reimbursement. Addition- University Medical Center (HUMC) and coally, clinical trials will provide us with the managing partner of the Northern New Jersey
information needed to determine whether Cancer Center (NNJCC), the private physicians
allogenic stem cells, which are those foreign practice group affiliated with the HUMC. Pecora
to you, or autologous stem cells, which are received his medical degree from the University
ones that are your own, should be used for of Medicine and Dentistry of New Jersey, graduparticular therapies.
ating with honors. He went on to complete his
There are distinct advantages to using both medical education in internal medicine at New
cell types. While allogeneic cells will not nec- York Hospital and in hematology and oncology at
essarily cause damage, it is inherently safer Memorial Sloan-Kettering Cancer Center in New
to use autologous cells rather than ones com- York City. He is board-certified in internal mediing from another person. Many times, people cine, hematology and oncology. He also received
who are diagnosed with a disease and in turn a degree in medical management.
The future of stem cell therapies
relies in part on the ability to
educate the public on the
benefits of these therapies.”
trial pipelines, as well as recent market activity by numerous large pharmaceutical companies. In 2009, Pfizer Inc. announced an
initiative with Athersys, a clinical-stage biopharmaceutical company, for the development of a stem cell therapy to treat inflammatory bowel disease. In April 2010, Dendreon
received U.S. Food and Drug Administration
(FDA) approval for Provenge, an immunotherapy for prostate cancer that uses a
patient’s own white blood cells to attack cancer cells. Later that year, Cephalon made a
$130-million, cash-upfront payment to Mesoblast, a developer of innovative biological
products for regenerative medicine, for the
rights to specific stem cell technology products. These ventures exemplify the growing
trend toward and investment in cellular therapies, which hold the promise to reverse some
chronic diseases—so it’s like the patient never
even had the disease.
A prime example of a chronic disease that
can be managed through cell therapy is cardiovascular disease. Despite many advances
in the medical field, heart disease remains the
leading cause of death in the United States.
Adult stem cell therapies, however, are currently being developed for the treatment of
damaged heart muscle following an acute
myocardial infarction. The therapies work to
school
perform best on standardized tests, yet
these are the school districts that commonly have clientele from the highestperforming demographics. A contrary
thought would be recruiting and
rewarding high-performing teachers
to take on the challenge of the toughest
demographics. We don’t send Navy
Seals to Disney World.
What can you as a life-science professional do to contribute to our
nations STEM challenge this academic
year now underway? Here are a few
thoughts.
Science teachers have little to no
budget; contribute to community
foundations that give grants to educators. Mentor a science fair student or
be an encouraging judge. Sponsor a
science fair award. Support a science
museum. Take a few kids for a walk in
the woods. Be a mentor to a disadvantaged youth. Open your business to
tours by small numbers of 12-yearolds. With six at a time, you can amaze
and inspire.
Both of us were fortunate in our
youth to have been welcomed to tours
of commercial research centers, often
on a Saturday. What we saw cemented a lifelong interest in bettering life
through better science. The “wow”
factor in STEM did not come to us
from classrooms as much as it did
from parents and astronauts and little
transistor radios. STEM advances
one kid at a time, and it only takes one
to make a difference in this world.
Only 1 in 2,000 Americans are members of the American Chemical Society, while 100 percent of the population depends on chemistry, biology,
physics and math. Make it happen. If
you don’t, who will? ddn
Peter T. Kissinger is professor of chemistry at Purdue University, chairman
emeritus of BASi and a director of Chembio
Diagnostics, Phlebotics and Prosolia.
Candice Kissinger is an eighth-grade science teacher, adjunct professor of pharmacy at Purdue University and former senior
vice president of research at BASi.
Your Thoughts Here
------------------------------------------------------
Every month, Drug Discovery News will feature the
thoughts, opinions and important discoveries of our
readers on this page. It’s an opportunity for you to
sound off on the hot topic on everyone’s tongues
or to shine a light on an area you feel deserves
more attention.
We will consider previously published pieces,
though our preference is to publish original columns written for us and geared to our readers: the
30,000 lab managers, lead researchers and
researchers who read us every month. Columns
should be between 700 and 1500 words and be
accompanied by a picture of the author.
To discuss an idea for a guest commentary
submission, contact Amy Swinderman, chief editor,
at [email protected].
b r i e f s
Stepping
up to the
platform
Vela, Eppendorf announce
plans for diagnostic platform
SINGAPORE—Vela
Diagnostics and Eppendorf
have established a collaboration for joint development of an in-vitro diagnostic RNA/DNA extraction platform. The Sentosa SX system is based
on Eppendorf’s pipetting and liquid handling
technology and Vela’s in-vitro diagnostics and
workflow solutions. Per the agreement, scientists
from both companies have customized Eppendorf’s epMotion system with a diagnostic workflow and features exclusive to Vela Diagnostics.
“Our collaboration merges an already robust
epMotion with revolutionary system enhancements. The new customized hardware and software on the Sentosa system will enhance workflow efficiency in laboratories and improve
sample traceability. It will be easier for lab staff,
and they can maximize their time in other valueadding tasks,” Michael Tillmann, CEO of Vela
Diagnostics, said in a press release.
CRB, LI-COR ink license
deal for peptide labeling
CLEVELAND, United Kingdom— Cambridge
Research Biochemicals (CRB) has signed a nonexclusive license with LI-COR Biosciences for the
development, manufacturing and sale of IRDye
and IRDye QC-1 near-infrared dye-labeled peptides for research use only. The partnership is one
of many license agreements CRB has enacted to
provide the largest possible selection of dyes for
peptide labeling, with other partners including
Life Technologies, GE-Healthcare, Atto-Tec, Cyanagen and Biosearch Technologies.
“The expertise and quality for custom peptide
synthesis from CRB, coupled with LI-COR dye
technologies, will enable our customers to create innovative solutions for their research
needs,” Bambi Reynolds, licensing and intellectual property manager of biotechnology at
Li-COR, said in a press release.
Distribution agreement
for Asia, Latin America
LUND, Sweden—Genovis and Sigma-Aldrich
Corp. recently announced the establishment of
an exclusive distribution agreement to enable
the sale of Genovis products in roughly 50 countries across Asia, Southeast Asia and South
America. The agreement grants exclusive rights
in the aforementioned regions and includes
existing products in Genovis’ protein-engineering
portfolio, and covers biosimilar and therapeutic
antibody QC tools and antibody fragmentation
and deglycosylation enzymes.
“[We] have signed an agreement with one of
the world’s strongest players in supplying the
life-science community with biochemical and
organic chemical products, kits and services.
Our goal is to reach out to the rapidly growing
Asian and South American markets, and this is
an excellent solution for us,” Sarah Fredriksson,
CEO of Genovis, said in a press release.
NCKU, Fujitsu ink MOU
to build genomics platform
By Kelsey Kaustinen
notes in substitution for outstanding notes
previously issued by CollabRx. In addition,
Tegal will grant a total of 368,417 restricted
stock units and options as “inducement
grants” to newly hired management and
employees, all subject to four-year vesting and
other restrictions.
The CEOs of the two companies, Thomas
Mika of Tegal and James Karis of CollabRx,
will serve as co-CEOs of the combined, publicly traded company, with headquarters in
San Francisco. Tegal entered into an employment agreement with Karis that will become
effective at the closing and he will also be
appointed to Tegal’s board of directors. Tegal
will continue to operate under its current name
and ticker symbol for now, but plans to seek
stockholder approval in September 2012 for an
amendment to its certificate of incorporation,
changing its corporate name to CollabRx Inc.
“This acquisition marks both the successful
conclusion of a transition process and the
beginning of a new chapter for Tegal Corp.,”
TAINAN, Taiwan—National Cheng Kung
University (NCKU) of southern Taiwan
and Fujitsu Taiwan Ltd. recently
announced the signing of a memorandum of understanding (MOU) to build
a comprehensive genomics research
platform. The platform will consist of
genomics and bioinformatics research,
and the parties seek to jointly promote
computational biology, develop personnel training for bioinformatics and also
develop biology analysis software.
Dr. Hwung-Hweng Hwung, president of NCKU, called the partnership
one based on shared benefits and
strong collaborations. Hwung and Ikegami Ichirou, the general manager of
Fujitsu Taiwan, signed the MOU for
their respective institutions.
“NCKU’s research on genomics and
the original species of Taiwan has shown
great achievement and its extensive relations with world-renowned scientific
institutes are fruitful in collaborated
results,” said Ikegami in a press release,
noting that NCKU is home to distinguished researchers and represents the
first university in Taiwan that Fujitsu
has looked forward to working with.
Chi-Chuan Hwang, chair professor
of NCKU Engineering Science, said in
a press release that the initial focus will
be on developing talents, and then collecting data on original species found
in Taiwan and training personnel to
work with biology data analysis. NCKU
brings with it experience in engineering research while Fujitsu offers its
input as a leading Japanese information
and communication technology company. The resulting platform will
explore important genomics research
issues, and is expected to increase
NCKU’s participation in global genetics
research. NCKU and Fujitsu will share
research and development results.
Both organizations have been active
in establishing and furthering new
p a r t n e r sh ip s . Fu j it su Ir e l a n d
announced earlier this month that
Fujitsu Laboratories Ltd. was beginning a significant investment in a
tegal continued on page 15
ncku continued on page 15
Life Technologies’ Ion Proton Sequencer is designed to sequence an entire human genome in a day for
approximately $1,000 using semiconductor chips to map human exomes and genomes.
Eyes on the Ion
Life Technologies and
Boston Children’s Hospital
to develop optimized lab
workflow based on
Ion Proton Sequencer
By Jeffrey Bouley
BOSTON—Boston
Children’s Hospital, which
touts itself as the home of the world’s largest
pediatric research enterprise, and Carlsbad,
Calif.-based Life Technologies Corp. in late
June announced a research and development
collaboration to develop an end-to-end genetic sequencing lab workflow based on Life
Technologies’ Ion Proton Sequencer.
In this effort, the two parties plan to collaborate on the development of an optimized
laboratory infrastructure and lab protocols
for an advanced sequencing facility that will
be built at Boston Children’s Hospital in compliance with CLIA and CAP certification
standards.
Dr. Paul Billings, chief medical officer at Life
Technologies, says the opportunity to partner
with Boston Children’s Hospital is exciting
because it offers a chance to collaborate with
world-renowned experts in pediatric genetic
disease and demonstrate best practices for
using the Ion Torrent sequencing platform,
adding, “Partnerships like these are essential
ion continued on page 13
Tegal acquires CollabRx
Deal brings interpretive
content and data analytics
to genomics-based medicine
By Lloyd Dunlap
PETALUMA, Calif.— Tegal
Corp. recently
announced the closing of an agreement to
acquire CollabRx Inc., a privately held technology company in the rapidly growing market of interpretive content and data analytics
for genomics-based medicine.
Tegal will issue 236,433 shares of common
stock, representing 14 percent of its total
shares outstanding prior to the closing, to
former CollabRx stockholders in exchange for
100 percent of the capital stock of CollabRx.
Tegal and certain former CollabRx stockholders entered into a stockholders agreement
providing for, among other things, registration rights, transfer restrictions and voting
and standstill agreements. Tegal also assumed
$500,000 of existing CollabRx indebtedness
through the issuance of five-year promissory
TOOLS & TECHNOLOGY
ion
to our medical sciences strategy as
we seek to assist researchers in discovering improved diagnostics and
treatments for genetic conditions.”
For his part, Dr. David Margulies,
director of the Gene Partnership
Program at Boston Children’s Hospital, anticipates that the hospital
will benefit from Life Technologies’
“leading expertise in DNA sequencing technology and bioinformatics”
being added to the clinical research,
genomics and informatics expertise
of Boston Children’s Hospital.
“This collaboration is an important first step toward providing
informed, personalized care for
patients whose conditions are difficult to treat,” according to Margulies. “The development of an optimized laboratory infrastructure will
support our mission of providing
the highest-quality, innovative and
cost-effective care to our patients.”
The Ion Proton Sequencer is
designed to sequence an entire
human genome in a day for approximately $1,000. Unlike traditional
next-generation systems, Life Technologies reports, it relies on semiconductor chips to map human
exomes and genomes, making it
much faster and less expensive to
analyze DNA “at unprecedented
throughput levels and generate
accurate sequencing data.”
The basic Ion Proton System is
structured around the same technology as its predecessor, the Ion Personal Genome Machine (PGM),
which is designed for sequencing
small genomes or sets of genes. Combined with the AmpliSeq targeted
sequencing technology, researchers
can sequence panels of genes associated with disease on the PGM or
exomes and genomes on the Ion Proton Sequencer in just a few hours,
according to Life Technologies.
The news of the Boston Children’s
Hospital deal followed a mere day
after an announcement that The
Hospital for Sick Children in Toronto, Ontario, Canada, had adopted
the Ion Proton Sequencer platform
as a key means to launch its new
Centre for Genetic Medicine. The
pairing with Life Technologies in
this case was characterized as a
“long-term partnership” that will
focus on sequencing 10,000 genomes
per year to “revolutionize” pediatric
disease research in Canada.
The Hospital for Sick Children
and Life Technologies reportedly
will collaborate on developing
sequencing workflows and protocols for the Ion Proton System that
are tailored for studies of interest to
researchers in the new center. The
first collaborative project will focus
on sequencing clinical research
samples to better understand the
genetics behind autism, with the
10,000 genomes per year effort to
study various diseases in children
being a longer-term goal.
“The perfect storm of unparalleled advances in genome sequenc-
ing technology and information science, and a captivated hospital striving for new ways to move forward
in medical treatment, bring us to
this important day,” said Dr. Stephen Scherer, co-director of the
Centre for Genetic Medicine, who
also leads the Centre for Applied
Genomics at The Hospital for Sick
Children. “We are very excited to
work with Life Technologies to
enhance our sequencing capabilities, such that ‘genomic surveillance’
may soon become the first line of
investigation in all clinical research
studies ongoing at our institution.”
“With the help of this new technology, we will be able to further
deepen our understanding of the
genetic basis of human disease and
translate this directly into daily
clinical practice,” added Dr. Ronald
Cohn, the other co-director of the
Centre for Genetic Medicine. “We
have finally reached a point where
individualized medicine is not just
a theoretical concept, but will
become an integral part of clinical
care and management.” ddn
“This collaboration is an important first
step toward providing informed,
personalized care for patients whose
conditions are difficult to treat. The
development of an optimized laboratory
infrastructure will support our mission of
providing the highest-quality, innovative
and cost-effective care to our patients.”
Dr. David Margulies, director of The Gene
Partnership Program at Boston Children’s Hospital
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TOOLS & TECHNOLOGY
KREATECH, ORIDIS go FISH
Companies to develop
state-of-the-art assays
for the oncology field
By Lloyd Dunlap
AMSTERDAM, The Netherlands—
KREATECH Diagnostics and ORIDIS Biomarkers have entered into
an agreement for the co-development and commercialization of
oncology-related DNA-FISH assays.
According to Sandor Snoeijers,
Kreatech’s business development
officer, “Kreatech and Oridis have
bundled their core competencies
because Kreatech’s expertise to
develop and manufacture customized REPEAT-FREE (RF) DNAFISH probes and Oridis’ ability to
access vast biobanks, combined
with their expertise as a highly valued CRO in clinical testing, will
result in high-quality RF DNA-FISH
assays optimized and validated on a
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statistical significant number of
patient samples, providing the endusers with a tremendous head start
in their clinical research.”
The application of FISH in
pathology is expected to continue to
grow in the future with a focus on
personalized medicine.
ORIDIS Biomarkers is a contract
research organization specializing in
cancer research, designing and performing retrospective and prospective custom-made tissue and body
fluid studies, integrating clinical data
and molecular pathology analysis.
“By combining Kreatech’s expertise in producing high-quality
probes with our experience in clinical assay development, we have created the perfect partnership. We are
very excited by the prospect for
follow-up products, and regard this
collaboration as the start of a promising product pipeline,” says Oridis
CEO Burkhard Feurstein.
“We expect the demand for the
molecular characterization of
tumors will strongly increase for
the coming years,” Snoeijers adds.
“With the current speed of discovering new biomarkers, we think
opportunities will grow rapidly for
this collaboration in the oncology
segment.”
Kreatech will design, develop
and manufacture the RF FISH
assays. Oridis will validate and
optimize these assays on patient
material. In addition, Oridis will
assist in the identification of new
biomarkers that allow detection by
a DNA-FISH assay. The aim is to
address the growing demand for
companion diagnostic assays.
The first co-developed assay is
designed to detect amplification of
the fibroblast growth factor receptor 1 (FGFR1) gene. Amplification of
FGFR1 has been observed in several
cancer types including lung, breast,
prostate and bladder cancer, and
inhibition of FGFR1 is a promising
goal for target-focused therapeutic
intervention.
The official launch of the FGFR1
amplification test will be at the
European Congress of Pathology in
September in Prague. The test will
be marketed via two channels,
Snoeijers states, “via our current
sales infrastructure, directly in EU
countries and the U.S., and by our
worldwide distributors elsewhere.
End users will be mainly in the
research and pathology segments.
We will also use a key account
approach, selling direct to pharma
companies that are developing
FGFR1 inhibitors, which might use
the assay for preclinical and stratification purposes.”
“By using Oridis’ expertise in
clinical testing and its access to
extensive biobanks, we have the
opportunity to bring our customized FISH program to the next
level,” says Kreatech CEO Kees
Moonen. ddn
The DREAM 7 challenge in part is meant to help researchers “understand how to
do experimental design when it comes to reconstruction of gene regulatory
networks, and understand how to create mathematical models, including what
parameters to use,” says the project’s leader and founder, Gustavo Stolovitzky.
dream
network inference and quantitative model building in systems biology.”
The initiative’s mission, according to its website, is “to assess how well
we are describing the networks of interacting molecules that underlie
biological systems … and how can we know how well we are predicting
the outcome of previously unseen experiments from our models?”
Three of the four challenges for this year’s DREAM 7 challenge
call for the development of informatics tools and methods that will
support ongoing efforts to treat cancer and ALS. Stolovitzky, a Yale
University Ph.D. and manager of functional genomics and systems
biology at IBM, notes that for this year’s challenges, DREAM organizers are partnering with the National Cancer Institute, Sage Bionetworks and Prize4Life, a not-for-profit organization that supports
efforts to discover treatments for ALS.
The NCI-DREAM Drug Sensitivity Prediction Challenge will
focus on using genomic information to build models that can estimate
the sensitivity of cancer cell lines to a set of small-molecule compounds—both alone and in combination. The goal is to understand
how well computational analysis of ‘omics data—including proteomics data, SNP data, gene expression data and drug dose response
data—can be used to predict drug activity in cell lines, and ultimately
to select the best treatments for patients based on genetic profiling
of tumors, Stolovitzky explains. The best-performing team will have
the opportunity to publish its results in Nature Biotechnology.
The second challenge for the year, organized with Prize4Life, will
attempt to develop methods that can predict the future progression
of ALS. Prize4Life is collecting data from ALS patients and, using
this data, the DREAM team will use combinations of mathematical
and statistical models to find a combination that defines fast and
slow progression of the disease. Emerging from this data may be
chemical differences that are at the causative root of ALS. Finally,
the team will try to determine what drugs would work best in each
patient’s case, Stolovitzky says. Prize4Life is offering a $25,000 prize
for the winning submission in this category.
The third challenge, created in collaboration with Sage Bionetworks, aims to develop algorithms for predicting breast cancer survival. The best performer in this category will have a paper published
in Science Translational Medicine.
The final challenge is “pure informatics” and focuses on network
topology and parameter inference. Participants are expected to develop optimization methods that accurately estimate parameters, predict
outcomes of perturbations and rewire networks in systems biology
network models. This challenge is meant to help researchers “understand how to do experimental design when it comes to reconstruction
of gene regulatory networks, and understand how to create mathematical models, including what parameters to use,” Stolovitzky says.
As its centerpiece, the DREAM process relies upon the wisdom
of crowds, a process based on the title of a book published in 2004
and written by James Surowiecki about the aggregation of information in groups and resulting in decisions that are often better than
could have been made by any single member of the group. Stolovitzky is a believer, arguing that an aggregate solution is better than
any single solution.
“Everyone knows a little bit about something, but knowledge is
diffused among many people. We distribute questions in such a way
that participants compete to provide their own important piece of
the truth,” he states.
He claims that aggregating the best results from teams in each of
the categories from previous challenges has resulted in improved
methods and better results. ddn
tegal
says Mika. “This is a mission Tegal’s
board has embraced wholeheartedly.
I am very pleased to be working with
James Karis as co-CEO and fellow
director, and look forward to building a dynamic company in a new era
of genomic medicine.”
Originally founded in 2008 by
Silicon Valley Internet pioneer and
cancer survivor Jay (Marty) Tenenbaum, CollabRx has developed clinical advisory networks, expert systems, proprietary tools and processes and a pipeline of commercial
data products for cancer. Ten years
ago, suffering from metastatic melanoma, Tenenbaum was given a year
TOOLS & TECHNOLOGY
ncku
research program with Digital
Enterprise Research Institute
based in NUI Galway, a program
that will focus research in networked knowledge. In late June,
Fujitsu Ltd., Fujitsu Laboratories
Ltd. and Nagoya University
announced that they had begun
joint research on the collection and
visualization of health information,
utilizing a wristwatch-style monitoring device and system developed by Fujitsu Laboratories.
In mid-May, NCKU announced
that one of its research teams, led
by Ming-Shi Chang, an NCKU professor in the Department of Biochemistry and Molecular Biology,
had discovered an anti-interleukin-20 antibody. The antibody is a
potential new anti-osteoporosis
and anti-rheumatoid arthritis drug,
and NCKU agreed to license select
intellectual property and transfer
appropriate technology to Novo
Nordisk AS for $13.3 million if the
project is successfully completed.
Prof. Chang and Novo Nordisk also
established a two-year research collaboration that would seek to
strengthen and possibly expand
potential uses of the antibody.
NCKU also held a seminar in
May regarding one of its longerrunning industry-academic collaborations with Delta Electronics.
Now in its fourth year, that effort
has spawned 60 published collaborative projects.
The university’s latest partnership consists of the signing of
three MOUs with AECOM, a U.S.based technical services company,
that focus on environmental protection and city development by
way of scientific and technical
interaction, water research and
natural disaster assessment. ddn
“Medicine is entering
a new era of low-cost
genome sequencing
and the proliferation
of personalized
treatments based on
specific genetic
mutations.”
James Karis,
co-CEO of CollabRx
to live. He researched various experimental drug treatments, and credits a failed cancer vaccine, among
other drugs, for saving his life.
CollabRx offers cloud-based systems that provide clinically relevant
interpretive knowledge to institutions, physicians, researchers and
patients for genomics-based medicine in cancer and other diseases to
inform healthcare decision-making.
Its access to clinical and scientific
advisors at leading academic institutions and a suite of tools and processes that combine artificial intelligence-based analytics with proprietary interpretive content could
position CollabRx well in the $300
billion value-added “big data”
opportunity in the U.S. healthcare
market (as reported by McKinsey
Global Institute), over half of which
is said to target cancer and cancer
genomics.
CollabRx Therapy Finders, the
company’s first commercial product, provides personalized and
actionable information to physicians and patients for rapidly determining the medical tests, therapies
and clinical trials that may be considered in cancer treatment planning, with a specific emphasis on
the tumor genetic profile.
“Medicine is entering a new era
of low-cost genome sequencing and
the proliferation of personalized
treatments based on specific genetic
mutations,” says Karis. “With the
technology platform and expert system leadership position that CollabRx has developed over the past
few years, we believe that the new
company is in a position to lead the
market for accurate, credible and
current genomic information in the
cancer space.” ddn
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b r i e f s
BD secures license to
Asuragen’s MDx technology
AUSTIN, Texas— Asuragen
Inc. recently
announced that it has granted Becton, Dickinson and Co. (BD) non-exclusive worldwide rights
to incorporate Armored RNA technology into its
in-vitro molecular diagnostics products. Armored
RNA, jointly invented and developed by Asuragen
and Cenetron Diagnostics, is a franchise technology for creating RNA and DNA standards for
molecular diagnostic assays. Per the terms of
the agreement, Asuragen will develop and supply reagents for BD Diagnostics. Financial terms
and other details were not disclosed.
“We’re pleased that yet another worldwide
leader in molecular diagnostics has chosen
Armored RNA technology for its in-vitro molecular
diagnostic kits. Armored RNA controls, due to the
nature of their reliability and integrity, have become
the industry standard in a wide range of diagnostic tests,” said Dr. Matt Winkler, CEO of Asuragen.
Trovagene, MD Anderson
target KRAS mutations
SAN DIEGO—Trovagene
Inc. has unveiled a collaboration with the University of Texas MD Anderson Cancer Center on the detection of transrenal
KRAS mutations in the urine of patients with pancreatic cancer. No financial details were disclosed.
Recent estimates highlight KRAS mutations as
being present in more than 90 percent of pancreatic cancers. Trovagene recently completed the
development of digital PCR assays for detecting
most prevalent KRAS mutations, including those
that account for roughly 95 percent of the KRAS
mutations found in pancreatic adenocarcinomas.
“The reliable detection and quantification of
both KRAS mutations and wild-type molecules
from urine could eventually lead to a sensitive
method for staging tumors before treatment and
detecting minimal residual disease after treatment,” Dr. Charlie Rodi, chief technology officer
at Trovagene, said in a press release.
Licensing agreement
formed by PDI, Polymedco
SASKATOON, Saskatchewan—A
commercial
licensing agreement has been announced
between Phenomenome Discoveries Inc. (PDI) and
Polymedco Cancer Diagnostic Products LLC
(Polymedco) which grants Polymedco rights to
commercialize PDI’s diagnostic blood test for the
assessment of colorectal cancer risk. PDI has discovered that roughly nine out of 10 patients with
colorectal cancer are deficient in novel anti-cancer
and anti-inflammatory metabolites, and has developed a blood test assayed by triple quad mass
spectrometry that can detect such deficiencies. In
a recent clinical trial, the test detected over 85
percent of cases of early-stage colorectal cancer.
Dr. Dayan Goodenowe, president and CEO of PDI,
noted in a press release that the companies had
jointly submitted an application for U.S. Food and
Drug Administration premarket review.
Custom-tailored therapy
Merrimack and CTCA
partner to advance
translational research
and individualized
treatment
By Jeffrey Bouley
CAMBRIDGE, Mass.—Merrimack
Pharmaceuticals Inc. and the
Schaumburg, Ill.-based Cancer
Treatment Centers of America
(CTCA) recently announced a
partnership to advance their longterm vision of individualized
treatment wherein diagnosis and
therapy is guided by an in-depth
understanding of the underlying
mechanism of a patient’s disease.
The collaboration encompasses research on diagnostics based
on a network signaling approach
to analyzing patients’ tumors as
well as clinical trial research. For
the diagnostic research aspect of
this collaboration, CTCA will
contribute archived tumor biopsies from its extensive tumor
databank as well as prospectively
collected tumor samples. These
samples will be analyzed using
Merrimack’s Network Biology
approach for identifying the network signaling that drives cancer
growth with the goal of understanding each patient’s cancer at
the molecular level.
“One of the questions Merrimack likes to ask is, ‘What is this
tumor addicted to for its growth?’
and the answer to that is powerful,
because then you can sample a
tumor and use the technology to
answer that in real-time with an
efficiency that lets you immediately incorporate that into a
patient workup and treatment
plan,” says Dr. Donald T. Braun,
vice president of clinical research
at CTCA. “The fact that they have
tailor continued on page 17
CTCA contributes to the collaboration with Merrimack a huge selection of
archived tumor biopsies as well as prospectively collected tumor samples. These
samples will be analyzed using Merrimack’s Network Biology approach for
identifying the network signaling that drives cancer growth with the goal of
understanding each patient’s cancer at the molecular level. “The fact that they
have a system to address growth dependency in tumors is extremely important to
us, and the fact they used that information to guide the development of new
therapies to block those growth pathways is important to us,” says Dr. Donald T.
Braun, vice president of clinical research at CTCA.
Breaking the
Parkinson’s
bottleneck
Luminex says its acquisition of privately held molecular diagnostics company GenturaDx and the resulting
combination of its MultiCode-RTx chemistry and GenturaDx’s PCR system is expected to produce a marketleading system for molecular diagnostic testing.
By Kelsey Kaustinen
AUSTIN, Texas—Luminex Corp. has announced
the signing of a definitive agreement with privately held GenturaDx, under which it will
acquire the molecular diagnostics company.
Per the terms of the agreement, Luminex will
purchase all of GenturaDx’s outstanding
shares for $50 million in cash, subject to
working capital reconciliation, as well as
potential additional contingent consideration
By Jim Cirigliano
based on product revenue performance and/
or the achievement of certain future milestones. Luminex expects the acquisition to be
dilutive in 2012, and expects it to add roughly
$6 million to its operating expenses in 2012,
excluding acquisition-related expenses.
GenturaDx is currently developing a fully
integrated, highly automated, real-time PCR
system that utilizes a single-use cassette for
sample-to-answer workflow. The system is
currently in late-stage development, and the
combination of GenturaDx’s PCR system
SUNNYVALE, Calif.—A new collaborative
effort between the renowned Parkinson’s Institute and Massachusettsbased pharmaceutical company Berg
Pharma aims to unlock critical information about Parkinson’s disease that
could speed the development of new
therapies and diagnostic methods.
This partnership brings together two
natural allies in the fight against Parkinson’s disease. The Parkinson’s Institute has deep expertise and an international reputation as a stand-alone institution focused entirely on researching
and treating the disease. Berg Pharma
brings to the table its trademarked
Interrogative Biology platform, which
it will use to analyze the mountain of
data the Parkinson’s Institute holds in
its numerous lines of cells and tissue
pcr continued on page 19
pi continued on page 19
Going primetime
with real-time PCR
Luminex acquires
GenturaDx for $50 million
Berg Pharma partners
with Parkinson’s Institute
to identify biomarkers in
Parkinson’s disease
tailor
a system to address growth dependency in tumors is extremely important to us and the fact they used that
information to guide the development of new therapies to block those
growth pathways is important to us.”
One of the key strengths that
CTCA offers Merrimack, in turn, is
that many of CTCA’s patients are
battling advanced cancer and have
received many—if not all—of the
standard lines of therapy. CTCA has
regional destination hospitals in
Chicago, Philadelphia, Phoenix and
Tulsa, with a fifth hospital opening
in Atlanta in 2012, providing a wide
variety of patient samples and data
from a large patient population. This
makes CTCA’s tumor archive particularly valuable, the partners say,
because it offers an opportunity for
Merrimack to explore how the
molecular characteristics of a tumor
change as a result of therapy. This
joint effort, they say, could eventually lead to the identification of novel
companion diagnostics to guide
treatment decisions.
“This partnership with Merrimack supports our goal to give every
patient an individually focused
treatment plan, using innovative
technologies and tools to help fight
their cancer and improve their quality of life,” said Dr. Maurie Markman, senior vice president of clinical
affairs and national director of medical oncology at CTCA, in an official
statement about the deal. “We
believe that the innovations that
come from this partnership could
help provide the right treatment for
every patient’s unique biology.”
“Access to CTCA’s tumor samples
greatly enhances the speed and
scope of the research we are doing
to understand the complexity of
cancer cells and to characterize
what their growth is dependent
upon,” added Robert Mulroy, CEO
of Merrimack, in the news release.
“CTCA is a great example of a forward-looking institution trying to
change the face of cancer care. This
collaboration represents the future
of individualized treatment where
a hospital and a biopharmaceutical
company work together on
research, which we hope will ultimately result in much better treatment for cancer patients.”
One of Merrimack’s key goals is
to ensure that with every therapeutic it develops, it also co-develops a
companion diagnostic, Gavin MacBeath, a founder of Merrimack and
its vice president of translational
research, tells ddn. “Our long-term
goal is to find ways to predict which
patients will respond to our drugs
based on biomarker profiles or
other information, so that’s how our
goals aligned so well with CTCA,
since they want to provide the best
possible targeted therapies as well.”
“CTCA’s key strength is they
have a lot of experience with treating patients and understanding the
lifecycle of cancer and specifically
various cancer indications and how
patients respond to different drugs
and at different stages in the lifecycle of the disease,” MacBeath
adds. “Also, with their treatment
aspect, they have a very well-developed network of patients and organizations to provide data that
advances translational research.
From Merrimack’s perspective, we
bring a deep understanding of the
biology behind cancer and quantitative models that predict how cells
will respond depending on the status of the cell and the agent it is
diagnostics
exposed to. We have five compounds in our pipeline, and soon to
be six, that are in clinical trials
along with the biological knowledge that led to the discovery of
those drugs.”
The parties say the collaboration
also encompasses clinical research.
“We think that working with
CTCA will be good for both parties,
and especially in providing the
material we need to help us develop
companion diagnostics,” MacBeath
says. ddn
One of the strengths Merrimack brings to this collaboration with CTCA is a deep
understanding of the biology behind cancer and quantitative models that predict how
cells will respond depending on the status of the cell and the agent to which it is exposed.
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diagnostics
Lilly, PrimeraDx break the ICE
Companies team up to
develop companion
diagnostics
By Amy Swinderman
MANSFIELD, Mass.— With the goal of
Lilly’s deal with PrimeraDx is similar to several others the pharma has made in recent
years—with Almac, Avid Radiopharmaceuticals and Qiagen, to name just a few—as it
looks to bolster its diagnostics capabilities.
“
bringing the much-ballyhooed concept of personalized medicine to the
clinic, global pharma Eli Lilly & Co.
has entered into a multi-year quest to
develop diagnostic products with
privately held PrimeraDx.
waters.com
Oasis® µElution SPE plates and UPLC®/MS/MS
have significantly increased throughput and
improved detection limits.
Bernard Cahay
Galephar Pharmaceutical Research, Belgium
100
Under the agreement, the companies will collaborate on the development of multiplex assays on PrimeraDx’s clinical platform, the Integrated Capillary Electrophoresis
Multiplex (ICEPlex) System. Financial terms were not disclosed.
ICEPlex combines polymerase
chain reaction (PCR) with capillary
electrophoresis to create a benchtop
instrument with the ability to deliver highly multiplexed and quantita-
”
LOD of Peptide Desmopressin from Human Plasma
%
A. Matrix blank
0
0.50
1.00
1.50
2.00 min
%
100
0
1.04
138
0.50
1.00
Baseline
x5
1.50
B. 1 pg/mL
spiked sample
2.00 min
In just 20 seconds per sample, Oasis µElution
plates provide 15x analyte enrichment of small
sample volumes without time-consuming evaporation
and reconstitution. T he unmatched efficiency and
reproducibility of this patented technology provide
the power scientists need to solve the most difficult
sample preparation challenges.
To see what other scientists are saying, visit
www.waters.com/impact
Pharmaceutical & Life Sciences | Food | Environmental | Clinical | Chemical Materials
tive information to the clinic. Users
can easily design very complex multimodal assays that test for disparate target types, like single-nucleotide polymorphisms (SNPs),
expression biomarkers, microRNAs and fusion genes.
According to PrimeraDx, a genotyping test for 20 mutations would
require five tubes in a conventional
qPCR system, whereas ICEPlex can
perform the entire reaction in a
single reaction tube. This, along
with probe-free amplification
chemistry, allows for simpler assays
that are easier to develop, validate,
manufacture and present to regulators, the company says.
PrimeraDx intends to sell the
system in an “Open Platform Mode”
to clinical labs and to collaborate
with pharmaceutical companies to
develop high-value companion and
enabling diagnostic products.
“We have great expectations of our
collaboration with PrimeraDx,” said
Dr. Andrew Schade, senior director
of Lilly’s clinical diagnostics laboratory, in a statement announcing the
collaboration. “The unique ability of
the ICEPlex System to combine multiple DNA and RNA biomarkers into
a single multiplex assay could prove
invaluable in our drive to develop
companion diagnostics for crucial
assets in our clinical pipeline.”
The collaboration will initially
focus on developing companion diagnostics for oncology, with plans to
apply the research across other therapeutic areas later, Schade noted.
Tiffany Olson, vice president of
diagnostics at Lilly, told ddn in 2009
that companion diagnostics can
have a great impact on current cancer treatment trends, and building
Lilly’s diagnostics capability will
allow patients, payers and prescribers to know which characteristics or
biomarkers exist in which patients—
and in turn, which Lilly medicines
are likely to work in which patients,
and which are not.
“This offers many advantages
from earlier understanding of efficacy and target populations to potentially lower development costs and
improve outcomes for individual
patients,” she said. “We see opportunities for companion diagnostics
across approximately 40 percent of
our portfolio of pipeline molecules,
including many in cancer.”
Dr. Matt McManus, president and
CEO of PrimeraDx, said the partnership is a step toward PrimeraDx’s
achievement of its goal of “bringing
personalized medicine to the clinic
and being the leader in the highvalue companion diagnostics space.”
“These programs are a tremendous validation of our technology
and its utility in the development of
complex tests to better diagnose and
treat patients. We are very excited
about collaborating with Lilly on
these important programs,” McManus added. ddn
© 2012 Waters Corporation. Waters, The Science of What’s Possible, Oasis, and UPLC are trademarks of Waters Corporation.
PI
ConTinued froM pAge 16
samples that it has been collecting for nearly 30 years,
making it one of the largest collections of its kind in the world.
“This is perhaps the most
aggressive, robust relationship
to date to unite a wealth of
knowledge in combination
with a platform to illuminate
the data,” says Niven Narain,
president and chief technology
office of Berg Pharma.
The goal of the collaboration
is to identify biomarkers—
characteristics of cells that can
be objectively measured—that
correlate to the progression of
Parkinson’s disease in cells.
The inability to identify objective indicators that mark the
disease’s processes at the cellular level has been a major
bottleneck on the road to developing breakthrough therapies.
Instead, current treatments
must focus on alleviating Parkinson’s symptoms, which do
not typically manifest themselves until the disease has progressed relatively far, and can
be measured only subjectively.
“Currently there is a high
dependency on genomics,”
says Narain. “People are looking for clear cause-and-effect
relationships, and they’re simply throwing out the failures.
But what if you have two conflicting datasets or your science lies outside of the wellknown literature?”
The Interrogative Biology
platform uses artificial intelligence and algorithms to establish linkages among multiple
data sets that include not only
genomes, but also proteomes,
metabolomes and lipidomes.
The platform compares these
among cells in healthy and diseased states in the hopes of
identifying the outliers that
represent the signatures of
Parkinson’s disease processes
in cells. The result of running
the Parkinson’s Institute’s tissues and cell lines through the
platform will be a massive collection of new data, which may
hold the key—or at least a good
clue—to understanding and
treating a disease that has so
far remained enigmatic and
unyielding.
“The greatest success we can
hope for through this process
is to open a window to the cell
that will allow us to some day
diagnose and treat Parkinson’s
disease before physical symptoms manifest,” Parkinson’s
Institute Chief Operating Officer Clyde Taylor says.
“Being nimble, entrepreneurial and innovative are the
keys to unlocking this disease,” he adds. ddn
eDitConneCt: e081215
PCr
ConTinued froM pAge 16
with Luminex’s MultiCode-RTx
chemistry is expected to produce a
market-leading system for molecular diagnostic testing.
GenturaDx’s patented cartridge
design offers automated sample
extraction, amplification and detection, allowing for improved testing
throughput while it reduces handson time, turnaround times and
sample handling. The system
enables users to run a variety of
diagnostics
assays on up to 12 patients’ samples
simultaneously. Luminex is expecting that a variety of assays that can
be used with the system will be commercially available by early 2014.
“Our proprietary technology provides a unique and unmatched
alternative to current sample automation for PCR technology,” Mark
N.K. Bagnall, president and CEO of
GenturaDx, said in a press release.
“I am confident that Luminex will
recognize significant strategic and
economic benefit from this acquisition and am pleased that our exper-
August 2012 • Drug Discovery News
tise and technology will help to fuel
continued growth of an established
industry leader like Luminex.”
Timothy Dehne, vice president
of global marketing at Luminex,
says the company had been looking
for a PCR platform of their own,
which the acquisition provides
along with a sample-to-answer system. Dehne notes that at least for
the short-term, Luminex will continue GenturaDx’s research and
development and production operations “to help us with a focus on
getting this product to market in
Speed
Convenience
Service
19
early 2014.”
“If you think about the breadth
of solutions that we can give to customers now, we can provide fullplex, real-time solutions that are
sample-to-answer, we can provide
diagnostic products that are higher
plex, multiplex products that can
do panel tests … and we can provide
protein analysis or nucleic acid
analysis with our x-map forms,”
says Dr. Jeremy Bridge-Cook,
senior vice president of research
and development at Luminex. ddn
eDitConneCt: e081213
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78897
b r i e f s
ILS forms genomics venture
RESEARCH TRIANGLE PARK, N.C.—Life-science
firm ILS recently announced its first acquisition
in the form of “key” assets of Beckman Coulter
Genomics in Morrisville, N.C. Following the acquisition, the company established a new venture,
ILS Genomics. The new venture will be headed
up by Sam Tetlow, ILS’ chief business officer. As
a result of the deal, ILS has now added gene
expression, molecular genotyping and biologics
product safety testing services to its repertoire.
“We are very pleased to add the top-flight
team from ILS Genomics,” Dr. TK Rao, chairman
and founder of ILS, said in a press release. “With
this purchase, ILS continues its investment in
people and innovative technology and is proud
to enhance Research Triangle Park, N.C., as the
leading biopharmaceutical hub in the United
States.”
BGI, CHOP team up
on rare diseases
PHILADELPHILA—BGI and The Children’s Hospital of Philadelphia (CHOP) recently announced
the joint launch of the 1,000 Rare Diseases Project, an undertaking that aims to accelerate the
discovery of genetic variants responsible for rare
diseases. The initiative will focus on sequencing
1,000 rare diseases, including those that affect
adults and children. Per the agreement, the companies will use next-generation sequencing technologies to analyze DNA samples from patients
and families with single-gene inheritance patterns.
“The BGI/CHOP collaboration … brings together the unique strengths of two world-class institutions, combining BGI’s robust capabilities and
expertise in NGS and bioinformatics analysis
with CHOP’s extensive biobanking and clinical
and translational expertise,” said Dr. Hakon
Hakonarson, who is director of the Center for
Applied Genomics at CHOP and co-director of
the BGI@CHOP Joint Genome Center.
VTT, GE Healthcare collaborate
on Alzheimer’s biomarkers
LASKUT, Finland—A recent collaboration between
VTT Technical Research Centre of Finland and GE
Healthcare will seek to validate a new Alzheimer’s
disease biomarker. The biomarker, a serum biochemical signature that can predict Alzheimer’s
progression months or years before the first appearance of symptoms, was discovered by researchers
from VTT and the University of Eastern Finland. GE
Healthcare began an alliance with Janssen Pharmaceutica NV in 2010 to develop diagnostic biosignatures for presymptomatic identification of
Alzheimer’s, and in conjunction with that program,
VTT will apply serum metabolite profiling to validate
the recently discovered biochemical signatures and
discover other novel biomarker candidates.
“We believe that integration of metabolomics
into GE’s and Janssen’s biosignatures initiative
will lead to better tools for early detection of AD
and may also lead to better therapeutic options,”
Zebrafish turn the tide in autism research
MIT researchers turn to
fish models to uncover
secrets of autism
By Lori Lesko
CAMBRIDGE, Mass.—Research biologists at the
Massachusetts Institute of Technology (MIT)
School of Science are counting on the small,
luminous bluish-black and silvery-gold
striped zebrafish to unlock the mystery of
autism. While the popular aquarium fish cannot display symptoms of autism, schizophrenia or other human brain disorders, the
organism is a useful tool for studying the
genes that contribute to such disorders—and
has the potential for new information on the
genes that cause autism, according to a study
led by Hazel Sive, associate dean and developmental biologist at MIT.
And while the zebrafish holds much promise for the future of treating, curing and possibly preventing autism from occurring, scientists are swimming against the current in
search of simple answers.
“We chose the fish as it is a wonderful system
to study genetic and molecular pathways that
underlie gene function in the whole animal,”
Sive tells ddn. “Assays can be much more extensive than they can be in mice over the same
timeframe. Since human and fish genes are
similar, we can almost always find a fish gene
that matches a human disease risk gene. And
since there is so little known about autism risk
genes and how they work, the zebrafish can be
an entry point to new analyses of such genes.”
Sive and her colleagues described their
findings in an article published in the online
edition of the journal Disease Models & Mechanisms (DMM). First, researchers isolated and
studied a group of about two dozen genes
known to be either missing or duplicated in
about 1 percent of autistic patients. Most of
the genes’ functions were unknown, but the
MIT study revealed that nearly all of them
produced brain abnormalities when deleted
in zebrafish embryos.
“Specifically, we wanted to know how many
genes in this region were necessary for brain
autism continued on page 23
Discovery
on demand
Merck Serono,
Compugen launch
company to
develop predictive
drug toxicity tests
By Kelsey Kaustinen
GENEVA—Merck Serono, a division of KGaA, and Compugen
Ltd. recently announced the
establishment of Neviah Genomics, a novel startup company that
will focus on discovering and
developing novel biomarkers for
the prediction of drug-induced
toxicity. The agreement comes on
the heels of a 2009 collaboration
between the companies for the
discovery of “biomarker signatures” for drug-induced toxicity.
“Following our prior successful collaboration with Merck
Serono, we are very pleased to
expand this relationship and
enter into this new and exciting
partnership. We are honored to
be the first Israeli company to
benefit from the establishment of
Merck Serono’s Israel Bioincubator and look forward to taking
our partnership to the next
level,” Dr. Anat Cohen-Dayag,
president and CEO of Compugen, said in a press release. “Furthermore, the formation of Neviah Genomics on a ‘discovery-ondemand’ basis enables Compugen to both continue its focus on
therapeutic monoclonal antibodies and therapeutic proteins in
the fields of immunology and
oncology, and provide potential
future benefits for our shareholders from our equity interest
in Neviah and royalties from
future product sales.”
Neviah Genomics will be operating out of the Merck Serono
Israel Bioincubator and is the
first company funded by the program. Merck Serono will be
responsible for providing initial
funding for Neviah Genomics,
while Compugen will employ
proprietary predictive discovery
technologies and receive an equity
toxicity continued on page 21
This graphic depicts a knockout of one autism risk
candidate gene studied by MIT called CORO1A and
shows that CORO1A is essential for normal brain and
eye development. In addition, it shows that the human
and fish CORO1A genes have similar functions.
Cold Spring
Harbor Lab, Pfizer
partner on cancer
therapy research
Collaborators aim to create nextgeneration short-hairpin RNA library
By Jim Cirigliano
COLD SPRING HARBOR, N.Y.—A recently announced collaborative
project between Cold Spring Harbor Laboratory (CSHL) and
Pfizer Inc. aims to develop a next-generation library of human
short-hairpin RNA (shRNA) for biomedical research, with the
hopes of identifying and validating drug targets and speeding
development of new cancer therapies.
“CSHL is pleased to partner with Pfizer to create a shRNA
technology platform that could speed the validation of drug
targets and open doors to new therapeutic options in a range
of cancers,” said CSHL President Dr. Bruce Stillman in the press
release announcing the partnership with Pfizer.
The focus of this collaboration will be on cataloguing shRNA
and a process known as RNA interference, which is a naturally
occurring technology within the body that activates or deactivates various genes.
CSHL professor Dr. Greg Hannon pioneered shRNA collections beginning with the comprehensive first-generation synthetic shRNA library he developed in 2004, which enables users
in industry and academia to identify and validate target genes
involved in a variety of diseases.
Researchers are learning to manipulate RNA interference in
order to purposefully turn genes on or off. Synthetic shRNA
molecules have already been used to silence the expression of
cshl continued on page 23
toxicity
ownership in the company, as well
as a right to royalties on future
sales. Specific financial details were
not disclosed.
“Neviah’s mission is to become a
state-of-the-art provider of toxicogenomic solutions for pharma
and biotech companies that are
looking to minimize attrition for
their preclinical candidate drug
and therapeutic leads,” says Simone Botti, head of Merck’s Israel
Bioincubator Fund and acting CEO
of Neviah Genomics. “There is a
very big unmet need for a fast and
efficient system that allows you to
easily identify candidates that
omics & systems biology
the Neviah deal.”
The new start-up will benefit
from the use of Compugen’s computational discovery platforms,
Cohen-Dayag says, in the search for
biomarker signatures for druginduced toxicity. Those signatures
will then be used to develop toxicogenomic diagnostic tests, for
which Cohen-Dayag notes there is
a growing market need, and the
resulting diagnostic tests will be
used to predict drug-induced toxicity and integrated into a biomarker
platform in order to help prioritize
and develop drug candidates.
Merck Serono launched the
Merck Serono Israel Bioincubator
Fund in 2011 as part of Merck Serono Ventures, with the aim of promoting innovation by enhancing
connections between academic
research and the biotechnology
industry in Israel. The fund provides seed funding and access to
state-of-the-art laboratory facilities
within Inter-Lab, Merck Serono’s
Israeli research and development
center, out of which Neviah Genomics will operate. The company has
earmarked a total of approximately
$12.1 million for the Bioincubator
initiative, and according to Botti,
expects to invest in eight to 10
companies.
“Neviah Genomics is a perfect
illustration of our goals behind the
establishment of the Israel Biotech
Incubator: to leverage Israeli science and know-how and get access
to novel products and technologies
for the benefit of Merck Serono’s
core therapeutic areas,” Susan Herbert, executive vice president of
global business development and
strategy at Merck Serono, said in a
press release. “In this regard, we
are delighted to be collaborating on
our first investment with Compugen, one of the premier biotech
companies in Israel and a worldleading predictive drug discovery
company. We believe that our joint
technology and resources represent a unique basis for a startup to
enter this emerging field that has
the potential to significantly reduce
the risk of drug discovery and
development.” ddn
A better way to a better outcome.
“There is a very big
unmet need for a fast
and efficient system
that allows you to easily
identify candidates that
might have significant
toxic effects. Neviah is
going to develop
products that will
enable clients to test
their own drugs.”
Simone Botti, head of
Merck’s Israel
Bioincubator Fund
might have significant toxic effects.
Neviah is going to develop products
that will enable clients to test their
own drugs.”
Botti adds that Neviah Genomics’ current focus is hepatotoxicity,
“because it is one of the main
causes of termination of early
development of a molecule.” Eventually, the company might also
expand into other fields such as
cardiotoxicity. According to Botti,
Compugen stood out as a potential
partner due to its technology and
the companies’ previous business
relationship.
“We knew that Compugen could
bring its own computational prowess to support the project,” says
Botti. “The fact that Compugen had
proved themselves on an earlier
biomarker collaboration that we
had was also a factor in the decision,
and as a matter of fact, the strong
relationship and confidence that
was built from a previous project
certainly allowed us to accelerate
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Hit-to-lead
CellCentric and ZoBio enter
into partnership to develop
lead compounds against
epigenetic drug targets
By Jeffrey Bouley
LEIDEN, The Netherlands— ZoBio BV and
Cambridge, U.K.-based CellCentric have
begun working together to discover lead
compounds against CellCentric’s portfolio
of epigenetic therapeutic drug targets.
ZoBio will use its Target Immobilized
NMR Screening (TINS) technology to
screen its fragment library against targets
nominated by CellCentric. Hit-to-lead and
lead optimization activities will be further
supported by ZoBio’s biophysical and
medicinal chemistry research services.
“Epigenetics is an exciting, yet challenging, field. We feel that our unique combination of biophysical and biochemical
approaches yields significant advantages
in developing small-molecule inhibitors
of these targets with optimal drug-like
properties,” said Dr. Gregg Siegal, chief
scientific officer at ZoBio, in a statement.
According to Dr. Anthony Brown, scientific director at CellCentric, ZoBio’s
TINS offers a “unique opportunity to identify novel hit matter against our epigenetic
drug targets. The interaction with ZoBio
will allow us to expand the breadth of our
hit-finding capabilities and will accelerate
our ongoing drug discovery activities.”
Among the strengths that ZoBio brings
to the partnership is an array of biophysics
services to support fragment-based drug
discovery. These services form an integrated pipeline that includes fragment
discovery, nuclear magnetic resonancebased structural biology services and validation and characterization by such
orthogonal methods as surface plasmon
resonance. These capabilities reportedly
enhance the ability to discover fragment
inhibitors for variety of targets, including
kinases, protein-protein interaction, antivirals and membrane proteins such as
GPCRs and ligand gated ion channels.
Among CellCentric’s reported strengths
is its skill in targeting epigenetic processes
for new treatments for cancer and a network of leading researchers in some 30 labs
worldwide. Active programs at CellCentric
include inhibitors to histone methyltransferases and epigenetic enzymes that act via
ubiquitination. CellCentric says it has evaluated more than 50 unexploited epigenetic
targets across multiple target families.
Notably, in 2010, CellCentric licensed a
novel epigenetic discovery program to
Japan’s Takeda Pharmaceutical Co. for a
cancer program. CellCentric received an
unspecified upfront payment from Takeda
but also stood to gain from preclinical and
clinical milestones, in addition to royalties, with a total deal value of as much as
$200 million to CellCentric.
Although CellCentric is strongly
focused on cancer, the company notes,
“Epigenetics concerns the cellular processes associated with modification of
chromatin that lead to differential gene
expression. It helps explain why different
cells in the body develop to fulfill specialized functions, despite containing identical DNA information.” In addition to
errors in epigenetic mechanisms causing
leading to tumor formation, it can also lead
to neurodegenerative diseases, metabolic
disorders and inflammatory diseases,
meaning that the field has importance in
multiple therapeutic arenas. ddn
flu
is that it reduces the impact of the infection—a finding that can help other researchers better understand how flu can cause
severe infections and guide them in research
for new treatments.
Speaking more technically, the abstract for
the Science article says, “We report that segment 3 of the virus contains a second open
reading frame (“X-ORF”), accessed via ribosomal frameshifting. The frameshift product,
termed PA-X, comprises the endonuclease
domain of the viral PA protein with a C-terminal domain encoded by the X-ORF and
functions to repress cellular gene expression.
PA-X also modulates IAV virulence in a
mouse infection model, acting to decrease
pathogenicity. Loss of PA-X expression leads
to changes in the kinetics of the global host
response, which notably includes increases
in inflammatory, apoptotic and T lymphocyte-signaling pathways.”
The ultimate importance of this finding is
yet to be determined, though the feat of finding
a new gene after so many decades of influenza
research is nothing to sniff at, notes Digard, a
professor of livestock immunology at the Roslin Institute at the University of Edinburgh.
“Knowing the gene is there and showing it
matters in a mouse model of infection with one
strain of virus is the first step,” says Digard,
who says his current job title doesn’t do a good
job of explaining what he does, being a molecular virologist with some 25 years of experience
with influenza and formerly a senior lecturer
on influenza at the University of Cambridge.
“It gives us more clues about virus disease
mechanisms, but it’s going to be a lot more
work to understand whether all flu strains
behave the same way and to work out whether
we can exploit this understanding for better
control of the virus in humans or animals.”
So, while he says he doesn’t want to oversell
the finding, and there are no immediate implications for therapeutic or diagnostic breakthroughs, Digard emphasizes that it “reiterates
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Engaging and Influential Keynote Speakers Highlight SLAS2013
Mehmet Toner, Ph.D.
Helen Andrus Benedict
Professor of Surgery (Biomedical
Engineering), and Health Sciences and
Technology, Harvard Medical School;
Massachusetts General Hospital (MGH)
Presentation: Bioengineering and
Clinical Applications of the Circulating
Tumor Cell Microchip
Premier
Sponsor:
Sir Harold Kroto
Department of Chemistry
and Biochemistry
The Florida State University
1996 Nobel Prize in Chemistry
Presentation: Science and
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Charles Sabine
Emmy-Award Winning
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Presentation: A Perspective on
Living with Huntington’s Disease
PHOTO BY Kim Traynor
While the initial discovery of the previously unknown
PA-X influenza gene rests with Prof. Paul Digard,
currently at the University of Edinburgh, and the team
in his lab, it took several other universities and health
organizations on both sides of the Atlantic to fully
root out and characterize the gene.
the fact that when you have severe disease, a
lot of the damage comes from inappropriate
immune response rather than directly from
the virus, because when you knock out that
gene, we found that you don’t reduce viral
load. It’s just that at the point mice should be
beginning to clear out the virus, things go
wrong. So it points to the fact that in treating
severe flu or any other disease, it’s not just
about clearing the virus, but about making sure
the immune system is doing the right thing.”
Digard notes this might be a cautionary note
in particular for those who want to treat the flu
with immune modulators, noting, “you need to
get it right if you start altering immune response,
as it may not necessarily make things better.”
Digard explains that finding this gene has
been in part a happy accident and in part diligent teamwork between his lab and researchers at the Universities of Cambridge, Cork,
Edinburgh and Utah, the Institute of Systems
Biology in Seattle and the U.S. National Institutes of Health.
“Students in my lab had worked out that
there was a host-cell shutoff activity in segment 3 some time ago, and we could have written something up as long as six years ago,”
Digard says. “We didn’t because there were
some inexplicable bits of data that made it
clear we didn’t properly understand what was
going on. Around the same time, we got our
first sight of the ORF. Of course, I tried to link
the two things, but couldn’t put the pieces
together in a way that fit properly—this took
a collaborator with better knowledge of
unusual events during protein translation,
Andrew Firth, to propose the ribosomal
frame shifting mechanism that allows PA-X
expression. The third piece of the jigsaw came
from collaboration with Jeff Taubenberger,
through the happy link of a joint grad student,
Brett Jagger, that facilitated the animal and
microarray experiments to show the hidden
gene matters during infection.”
Reportedly, Jagger first noticed something
odd about the gene when he realized that one
part of it was incredibly similar across different
flu strains. Because flu viruses evolve so quickly, anything that remained constant, he thought,
must have some significant importance.
Researchers found when the virus gene PA-X
was active, mice infected with flu subsequently
recovered. When the PA-X gene did not work
properly, the immune system was found to
overreact, thus making the infection worse, and
did not help destroy the virus any quicker.
“It really was a collaborative effort to pull
this story together,” says Digard, who will
soon be publishing an article on yet another
hidden flu gene that was discovered and characterized almost solely in his lab. ddn
autism
development, and which were ‘dosage sensors’ that gave phenotypes
with small increases or decreases in
expression,” Sive says. “We wanted
to figure out which genes in this and
other genomic intervals work
together to confer copy number
dependent phenotypes, and to use
the fish to define potential diagnostics and therapies.”
In the DMM journal summary,
researchers explain that deletion or
duplication of one copy of the
human 16p11.2 interval is tightly
associated with impaired brain
function, including autism spectrum disorders, intellectual disability disorder and other phenotypes,
indicating the importance of gene
dosage in this copy number variant
(CNV) region.
Using the zebrafish as a tool, a set
of 16p11.2 homologs was identified,
primarily on chromosomes 3 and 12,
the study states. Use of 11 phenotypic
assays, spanning the first five days of
development, demonstrated that this
set of genes is highly active in that 21
out of the 22 homologs tested showed
loss-of-function phenotypes.
Most genes in this region were
required for nervous system development, the research found. In general, human genes were able to substitute for the fish homolog, demonstrating orthology and suggesting
conserved molecular pathways.
Furthermore, the researchers were
able to restore normal development
by treating the fish with the human
equivalents of the genes that had been
repressed, allowing researchers “to
deduce that what you’re learning in
fish corresponds to what that gene is
doing in humans,” Sive says.
Of the 25 genes in the central core
interval, it is hypothesized that dosage changes in one or more of these
genes underlie the pathologies associated with the 16p11.2 CNV.
However, the article also states that
the crucial genes in the 16p11.2 interval—and in many CNVs associated
with other disorders—are unknown.
The future for this research
includes further experiments to
understand the molecular pathways by which each gene works,
and whether each works together
with other genes in the 16p11.2 interval, as predicted by human genetic
data, the article concluded. This
information will help to define targeted assays in mammals and possibly guide therapeutic directions.
Since autism is thought to arise
from a variety of genetic defects, this
research is part of a broad effort to
identify culprit genes and develop
treatments that target them, Sive says.
“That’s really the goal—to go from
an animal that shares molecular
pathways, but doesn’t get autistic
behaviors, into humans who have the
same pathways and do show these
behaviors,” says Sive, who is also a
member of the Whitehead Institute
for Biomedical Research. ddn
cshl
many genes in rats, mice and
humans. This has numerous
applications in oncology, and creating a more robust next-generation library of shRNA molecules
promises to be an important step
toward identifying targets for
silencing gene expression and
validating drug targets in a broad
range of cancers.
The library of data generated by
the study is expected to be made
available both to the academic and
commercial researchers.
This collaboration combines
CSHL’s academic researching
capabilities and expertise with
Pfizer’s size and market clout.
Both partners see tremendous
benefits to collaborating on a
large-scale project such as this.
“Pfizer is pleased to be involved
in this partnership, which will
marry cutting-edge shRNA technologies with our efforts in cancer
genetics and complex tumor models toward the singular goal of identifying and validating novel targets
for cancer therapeutics,” Pfizer’s
oncology chief scientific officer, Bob
Abraham, said in a news release.
CSHL is a private, non-profit
research and education institution
devoted to molecular biology, with
applications in genetic disorders,
neurological disorders and cancer.
It is ranked no. 1 in the world by
Thomson Reuters for impact of its
research in molecular biology and
genetics. CSHL has been home to
eight Nobel Prize winners. Cancer
research at CSHL focuses on understanding cancer cells and cancer
processes at the cellular level.
To date, Pfizer’s cancer and chemotherapy pharmaceutical products include Camptosar, Ellence
and Sutent. ddn
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MagForce partners
with Mayo Clinic
BERLIN—MagForce AG and Mayo Clinic have
announced a preclinical research agreement
centered on MagForce’s NanoTherm therapy. Per
the agreement, Mayo Clinic will launch and fund
a research program applying NanoTherm to
investigate the preclinical efficiency of the therapy in pancreatic and liver cancers. Dev Mukhopadhyay, professor of biochemistry/molecular
biology, will direct the project, which aims to
achieve preclinical proof of concept in order to
file the clinical development program supporting
U.S. Food and Drug Administration premarket
approval of NanoTherm in these indications.
“A positive outcome of this new project would
be the first important milestone to set up a clinical
development program in gastrointestinal cancer
in cooperation with medical key opinion leaders
throughout the United States,” said Dr. Hoda Tawfik,
vice president of R&D/Medical Affairs at MagForce.
Collaboration
CoMMpass
targets complications to multiple
myeloma
treatment
Sanofi, Joslin Diabetes
Center to develop new
medicines to treat diabetes
and related disorders
By Ilene Schneider
PARIS—A collaboration between global pharmaceutical company Sanofi and the Joslin
Diabetes Center has the potential to be “an
alliance for early success in advancing science
to better serve the patient community,” in the
words of Dr. Nandan Pakudone, vice president of the Office of Commercialization and
Ventures at Joslin, a clinical, teaching and
research affiliate of Harvard Medical School.
After two years of discussions with leaders
in universities and research institutions,
Sanofi decided to ally with Joslin to enhance
its own offerings of insulin products by developing new kinds of insulin to work on specific
cell types.
The partnership to promote the development of novel therapeutic approaches for
diabetes and related disorders was announced
at the 2012 Bio International Convention in
Boston. It combines Joslin’s focus on “genomic
and other approaches to understand the
mechanisms of diabetes and its complications” with Sanofi’s ability to “translate discoveries and bring them to the clinic as quickly as possible, using its experience with using
medicinal chemistry and garnering regulatory approval,” explains Dr. Srideran Natesan, scientific site head of research and devel-
nistic drug discovery,” Santarelli stated in a
June 19 news release. “To establish a leadership position in this field, we sought to build
a solid partnership with Seaside Therapeutics, a company that has successfully pioneered the research and development in this
novel and uncharted area.”
ASD refers to a group of enigmatic cognitive disorders, including autism and Asperger’s syndrome, which impair social interaction and communication, whereas FXS is a
rare genetic disease, whose symptoms closely
resemble those of ASD and whose underlying
mechanism may be similar.
Drug companies are hopeful that new
drugs will be able to relieve some of the behavioral problems associated with ASD and FXS,
including poor impulse control, speech delays
and socialization problems.
The newly formed alliance aims to speed
up research and development in this field and
lead a fundamental change in the treatment
fragile x continued on page 27
commpass continued on page 26
SOUTH SAN FRANCISCO, Calif.—A recently estab-
MJFF funds KineMed
biomarker research
EMERYVILLE, Calif.— KineMed
Inc. has
announced the receipt of additional funding
from the Michael J. Fox Foundation (MJFF) in the
form of a $1.2 million award for the ongoing
development of kinetic biomarkers that could
potentially accelerate and reduce costs for trials
of Parkinson’s disease treatments. KineMed’s
program seeks to identify and develop biomarkers for disease progression and regression for
Parkinson’s disease in hopes of being able to
predict disease changes ahead of symptoms.
“The lack of validated biomarkers for
Parkinson’s disease is a major hurdle to PD drug
development today … KineMed’s cross-sectional study will look to confirm existing data that
we have funded, which has identified biomarkers
that are sensitive to subtle changes early in the
disease process,” said Dr. Mark Frasier, vice
president of research programs for MJFF.
Seaside Therapeutics is a privately held, 30-employee company headquartered in Cambridge, Mass., founded
specifically to develop disease-modifying therapeutics for fragile X syndrome and autism spectrum disorders.
A cognitive collaboration
Roche, Seaside Therapeutics
form alliance to discover,
develop new drugs for
fragile X syndrome, autism
spectrum disorders
By Lori Lesko
BASEL, Switzerland—Placing their rivalry in drug
development aside, Swiss pharmaceutical
giant Roche and Seaside Therapeutics, a privately held, 30-employee company headquartered in Cambridge, Mass., have forged a landmark alliance aimed at finding new treatments
for fragile X syndrome (FXS), autism spectrum
disorders (ASD) and mental retardation.
The deal will establish the biggest effort to
date in discovering new autism drugs, said Luca
Santarelli, global head of Roche Neuroscience.
“Recent discoveries in genetics have shed
light on the biological underpinnings of these
conditions, thus providing a basis for mecha-
By Jim Cirigliano
NORWALK, Conn.—The Multiple Myeloma Research Foundation (MMRF) has
announced a partnership with US
Oncology Research to undertake a
landmark, longterm clinical
study of multiple
myeloma’s (MM)
natural history
and its effects on
the body at the
molecular level.
MM is an incurable cancer of According to Dr.
the blood. An Robert Rifkin,
estimated 20,000 oncologist and
new cases are hematologist at the
diagnosed every Rocky Mountain
year, and close to Cancer Centers,
which is affiliated
100,000 patients with US Oncology
are currently liv- Research, during the
i n g w i t h t h e last few decades,
access to new
disease.
According to proteasome drug
Dr. Robert Rifkin, classes and stem
cell transplants is
oncologist and
improving the
hematologist at outlook for patients
Rocky Mountain with multiple
Cancer Centers, myeloma.
which is affiliated
with US Oncology Research, 20 years
ago, survivability among those diagnosed with multiple myeloma was very
poor—perhaps two to three years.
“Fortunately, during the past couple
of decades, we’ve gained access to a
host of new agents, including proteasome drug classes and stem cell transplants,” he says. “We’ve improved
patient survivability to 10 years or more
in some cases.”
Medical science still has a long way
to go, however. It has yet to be able to
diabetes continued on page 25
Fluxion, Stanford School
of Medicine team up
lished collaborative effort between Fluxion Biosciences Inc. and the Stanford University School of
Medicine is seeking to develop tests that will help
lead to more effective therapies for cancer patients.
Dr. Stefanie Jeffrey’s laboratory will use Fluxion’s
IsoFlux System to locate and analyze circulating
cancer cells, which break off from primary tumors
to enter the bloodstream and are known to contribute to cancer metastasis in carcinomas such
as breast, prostate, colorectal, lung and pancreatic cancer. The IsoFlux System uses proprietary
microfluidic technology to isolate rare cells, resulting in high-quality samples ready for downstream
analysis. The partners will be focusing on breast
and lung cancer pathologies, seeking to subtype
different forms of the disease in order to develop
more effective and patient-specific treatments.
MMRF and US Oncology
Research collaborate on
landmark clinical study
to advance personalized
treatments for incurable
blood cancer
RESEARCH & DEVELOPMENT
A bioscaffold for heart disease repair
ADAPT technology could
augment tissue repair
By Chuck Green
VICTORIA, Australia—More hope for the heart
might not be far off. Development of novel
tissue engineering technologies—which have
the potential to augment tissue repair in the
heart—is part of a research collaboration
between Allied Healthcare Group and Commonwealth Scientific and Industrial Research
Organisation (CSIRO).
Research will focus on the development of
Allied’s novel tissue engineering technology,
ADAPT, to treat tissue matrices for the delivery of adult mesenchymal stem cells on models of heart failure. The objective of this collaboration is to use the ADAPT technology to
produce a new platform for the delivery of stem
cells. Repair of cardiovascular tissue through
injection of a tissue bioscaffold and the attraction of cells to repopulate and replace the initial
scaffold is expected to yield a superior, longlasting regenerative medicine implant that
evolves into native tissue, says Lee Rodne,
Allied’s managing director. The advantage of
incorporating stem cells into a bioscaffold tissue product is that they are delivered directly
to the source and already are incorporated
into the tissue, Rodne explains.
ADAPT is differentiated by prevention of
calcium accumulation. Over the past 15 years,
companies have experienced no significant
progression in calcification prevention.
Achieving this has major long-term benefits
for surgeons repairing and/or reconstructing
tissue such as heart valves.
The partners’ goal is to develop one or more
products globally. Initially, the collaboration
will focus on cardiovascular disease and heart
failure. The bioscaffold technology could be
applied across a range of medical conditions,
Rodne adds.
“Ultimately, we see our bioscaffold being
applied to a range of stem cell products, rather
than bound to a single program or stem cell
company,” explains Rodne. ddn
diabetes
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opment at Sanofi in Cambridge,
Mass., and head of external innovation and partnering for the United
States’ northeast region.
“Like cancer, diabetes is moving
toward more personalized medicine,” says Natesan. “Some patients
encounter complications because of
genetic and epigenetic factors. We
want to create new medications and
invest in a device to monitor blood
glucose so that patients can be in
communication with their doctors
and help to control their food intake
to manage the disease more
effectively.”
To improve the lives of people
with diabetes and related disorders, the collaboration will focus on
four key areas to identify potential
new biologics or small-molecule
drug candidates for the treatment
of late complications of diabetes
and new insulin analogs with more
targeted efficacy. Research will also
address the challenges of insulin
resistance and personalized
medicine.
Using a co-development model
without a “silo approach,” both
parties will have access to intellectual property for internal research
use, Pakudone says. Under the
terms of the agreement, Sanofi has
options to commercialize the
results of the research and believes
that there is “tremendous commercial potential for therapies in seven
to 10 years,” Natesan adds.
Joslin cares for 25,000 patients
per year in 47 affiliated clinics in the
United States. Offering a “holistic
solution to diabetes,” Joslin also
does research into the mechanisms
of diabetes and its complications
and provides education and training programs for doctors, nurses,
educators, payers and other personnel, Pakudone says. The organization is especially focused on
diseases—such as eye, kidney and
heart—that emanate from
diabetes.
According to Pakudone, some
patients never encounter these
complications, “so clearly, certain
molecules protect them.” He adds,
“if we can identify these factors, we
can build better drug compounds
from these proteins to work on specific molecular pathways for certain
segments of the population.” ddn
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commpass
BMS says that Amylin’s diabetes assets are a good complement to its portfolio of Onglyza, Kombiglyze and Forxiga, the diabetes drugs
that BMS and AstraZeneca have been working on.
bms
offer and second-step merger, and
its total value—including Amylin’s
net debt and a contractual payment
obligation to Eli Lilly & Co.—could
be about $7 billion.
The acquisition is part of an
ongoing diabetes alliance between
BMS and AstraZeneca that will now
develop and commercialize Amylin’s portfolio of products, which
primarily consists of a franchise of
GLP-1 agonists for the treatment of
type 2 diabetes. That franchise is
anchored by two such treatments:
Byetta (exenatide) injection and
Bydureon (exenatide extended-
equate glycemic control on mealtime insulin; and a state-of-the-art
sterile production facility in Ohio.
These assets are a good complement to BMS’ portfolio of Onglyza,
Kombiglyze and Forxiga, the diabetes drugs that BMS and AstraZeneca have been working on, says
Mauer.
“By leveraging the existing AZ/
BMS diabetes sales force, our capabilities in access/affordability and
our marketing experience, we expect
that we will be able to significantly
broaden the prescriber base and
drive increased adoption of Amylin’s
GLP-1 franchise,” she adds. “We also
believe that Amylin’s U.S. endocrinology capability has the potential
By leveraging the existing AZ/BMS
diabetes sales force, our capabilities
in access/affordability and our
marketing experience, we expect
that we will be able to significantly
broaden the prescriber base and
drive increased adoption of
Amylin’s GLP-1 franchise.”
Jennifer Fron Mauer, director of
BMS business communications
release for injectable suspension/
exenatide 2 mg powder and solvent
for prolonged release suspension
for injection), both of which are
approved for use in the United
States and Europe.
“Our view is that to date, the
GLP-1 class has been predominately
prescribed by endocrinologists in
the United States,” says Jennifer
Fron Mauer, director of BMS business communications. “However,
we believe that there are many
patients not treated by endocrinologists who could benefit from these
medicines.”
Other assets included in the
acquisition are Metreleptin, a leptin
analog currently under review by
the U.S. Food and Drug Administration (FDA) for the treatment of diabetes and/or hypertriglyceridemia
in patients with rare forms of inherited or acquired lipodystrophy;
Symlin (pramlintide acetate) injection, an amylin analog approved by
the FDA for the treatment of types
1 and 2 diabetes patients with inad-
to enhance the promotion of our
Onglyza franchise business.”
Following completion of the
acquisition, AstraZeneca will make
a $3.4-billion cash payment to Amylin as a wholly owned subsidiary of
BMS. All of Amylin’s physical assets
will be owned by BMS, and AstraZeneca will be entitled to 50 percent
of the profits and losses arising from
Amylin’s business, as well as ownership of certain Amylin assets. Profits and losses arising from the collaboration will be shared equally. In
addition, AstraZeneca has the
option to establish equal governance
rights over key strategic and financial decisions regarding the collaboration upon an additional $135-million payment to BMS.
“This is a compelling proposition
that will have an immediate positive
impact on revenues and is fully in
line with our stated partnering
strategy to enhance top-line growth
and strengthen our late-stage pipeline,” said Simon Lowth, AstraZeneca’s interim CEO, in a statement.
“The broadening of our diabetes
collaboration with Bristol-Myers
Squibb is another important step
towards creating a leadership position in the treatment of a disease
with growing unmet medical need
that is reaching epidemic proportions in many areas of the world.
The combined development, regulatory and commercial strengths of
the AstraZeneca and Bristol MyersSquibb alliance for diabetes provides an excellent platform to
unlock the potential of Amylin’s differentiated treatments for the benefit of patients worldwide and for
our shareholders.”
The boards of directors of BMS
and Amylin have unanimously
approved the acquisition. At press
time, Amylin’s board had unanimously recommended that Amylin’s
stockholders tender their shares
into the tender offer. The deal was
expected to close by the end of July.
BMS will finance the acquisition from its existing cash resources and credit facilities. The pharma said it expected the transactions to be dilutive to non-GAAP
earnings per share (EPS) in 2012
and 2013 by approximately 3 cents,
becoming slightly accretive starting in 2014 and followed by meaningful accretion in the later part of
the decade.
As we went to press, no decisions
had been made about how Amylin’s
San Diego headquarters will be
incorporated into New York-based
BMS or how the acquisition will
affect Amylin’s employees.
“After the close of the acquisition,
we plan to work closely with Amylin’s leaders to gain a thorough
understanding of the portfolio, facilities and employees, and quickly
make decisions. Our goal is to ensure
the rapid integration of assets into
our operations,” says Mauer.
As to whether BMS is eyeing other
potential collaborations or add-ons
in the area of diabetes, Mauer notes,
“As part of our capital allocation
strategy, business development is a
priority for Bristol-Myers Squibb.
We continue to look for opportunities that can deliver long-term
growth. We focus on transactions
that are strategically, scientifically
and economically sound.”
Amylin declined to comment on
the acquisition. ddn
fully analyze the natural history of MM. Part of what makes the
disease so difficult to understand and treat is the fact that it arises
from multiple malignancies rather than from a single illness or
event—for example, toxic exposure followed by an infection. The
combination of factors leading to the development of the illness varies from patient to patient, making a one-size-fits-all therapy that
much more difficult to isolate.
Instead of looking for a single new therapy, this collaboration
between MMRF and US Oncology Research will be a foray into personalized medicine, with the hope of learning the molecular and
genetic changes that mark the progression of the disease and discovering ways to cater treatment to each individual case. This landmark study has been dubbed Relating Clinical Outcomes in Multiple
Myeloma to Personal Assessment of Genetic Profile, or CoMMpass,
and is supported by a $40 million investment by the MMRF.
“Our hope is that we will
quickly begin generating
hypotheses that can lead to
clinical trials,” says Anne
Quinn Young, vice president
of marketing at the Multiple
Myeloma Research
Foundation. “We’re in a
position to play a lead role
in connecting this data to
therapeutic advances.”
“This study is really a prototype of personalized medicine,” says
Dr. Carolyn Hoban, director of translational research at MMRF.
“The results may someday empower physician’s decision-making
regarding treatment options for their patients.”
“Our goal is to accrue 1,000 newly diagnosed multiple myeloma
patients and to use genome sequencing to identify new targets for
therapy, which could potentially lead to the development of a new
drug,” says Rifkin. “We would then be able to take it through development. We plan to follow the patients for a minimum of five years.”
At the outset, newly diagnosed MM patients’ tissues will be analyzed for quality and whole-genome sequencing. Their chromosomes
will be analyzed, and DNA and RNA samples will be extracted as
they begin therapy. Researchers will be able to observe these patients
going forward and return information in real-time, both to the doctors and to the patients. Finally, additional sets of tissue samples will
be taken at each relapse and at the time of failure of treatment, providing benchmarks to allow researchers to observe the molecularlevel changes that have occurred during the course of the disease.
The study also aims to create a “biobank” of serum and plasma
that can be further analyzed to look for better biomarkers to facilitate
new diagnostic and treatment options in future patients.
“We hope to discover more noninvasive diagnostic tools that will
minimize the discomfort to the patient,” Hoban says.
The collaboration between MMRF and US Oncology Research
marries two robust partners in the fight against multiple myeloma.
US Oncology Research represents a large community of MM patients
and physicians, as the organization sees roughly 20 percent of all
new MM cases, and has participated in 38 out of 40 U.S. Food and
Drug Administration-approved drugs. US Oncology Research is
already currently involved in about 100 other open trials, and will
be the principal investigator overseeing the CoMMpass study. Aside
from financial sponsorship of the CoMMpass study, the MMRF
brings to the table the technology and the science necessary to process the tissue samples and conduct the genome sequencing and
other molecular analyses.
The CoMMpass study already has two pharmaceutical partners—
Millennium and Onyx—that, in exchange for financial support of
the study, will receive priority access to the data it generates for a
six-month window, after which the data will enter the public domain.
Two or three additional pharmaceutical partners may be added to
the study later.
“Our hope is that we will quickly begin generating hypotheses
that can lead to clinical trials,” says Anne Quinn Young, vice president of marketing at MMRF. “We’re in a position to play a lead role
in connecting this data to therapeutic advances.”
“We need more collaborations like this between the medical and
patient communities and academia,” Rifkin says. “We’re off to a
good start.” ddn
fragile x
paradigm for FXS and ASD by
developing therapeutics that target
the molecular basis, and in turn,
core symptoms of these neurodevelopmental disorders.
The most commonly inherited
form of autism involves the gene
encoding FXS mental retardation
protein (FMRP). Loss of FMRP function disrupts signaling between neurons, leading to widespread brain
abnormalities and mental retardation. Normally, FMRP is balanced by
mGluR5, an important receptor in the
brain that is involved in learning and
memory. Without normal FMRP, this
balance is lost, leaving mGluR5 function unopposed. Early results from a
clinical trial suggest that children
with FXS can be helped by drugs that
inhibit mGluR5 activity.
Under the terms of the agreement, Seaside will license patents
covering the use of mGluR5 antagonists for the treatment of neurodevelopmental disorders exclusively
to Roche, while Roche subsequently
leads the development and commercialization of these compounds for
the treatment of ASD and FXS. Its
mGluR5 drug candidate, RG7090, is
currently enrolling patients in a
Phase II clinical trial in FXS.
The agreement also calls for Seaside to develop its GABA-B agonist
program and retain exclusive rights
to issue any pending patents covering the use of GABA-B agonists for
the treatment of FXS and ASD. Seaside’s lead GABA-B candidate,
STX209, is currently enrolling
patients in Phase III trials in FXS
and recently completed enrollment
in a Phase IIb trial in ASD.
Roche may exercise options to
commercialize STX209 upon completion of certain clinical development phases in FXS and ASD, but
Seaside will continue to lead the
clinical development of these programs. Additional terms of the
transaction were not disclosed.
Roche will get exclusive rights to
those patents from Seaside, as well
as the option to license commercial
rights to Seaside’s arbaclofen. That
drug, which works somewhat differently, is in late-stage testing for FXS
and in mid-stage testing for ASD.
Roche will provide an undisclosed
sum to help Seaside complete its
clinical trials of arbaclofen, according to the agreement. Seaside will
halt development of its own mGluR5
antagonist, which it licensed from
Merck, and will instead receive royalties on sales of Roche’s drug.
Darien E. Wilson, director of
public affairs at Roche, tells ddn,
“Roche has a strong research focus
in neuroscience and has been conducting research in autism-related
disorders for some time. Combining
our respective expertise in fragile X
and autism will hopefully produce
valuable insights for our drug
development program. There is still
much we don’t know about the biology of autism.”
Randall L. Carpenter, CEO of
Seaside, said Roche is the ideal partner for this venture.
“There is a long-history of scientific leadership and intellectual collaboration between Seaside and
Roche to further the development of
disease-modifying therapeutics for
neurodevelopmental disorders,”
Carpenter says. “We believe our
missions are aligned—which was a
driving force in selecting Roche as a
partner for Seaside. Roche has made
a strong commitment to neurodevelopmental disorders, and specifically
“One of the major advantages of this alliance is
that our combined efforts will yield multiple
shots on goal, with industry-leading pipelines of
programs specifically aimed at treating the core
symptoms of neurodevelopmental disorders.”
Randall L. Carpenter, CEO of Seaside Therapeutics
to serious conditions that have no
approved, effective or safe treatment. One of the major advantages
of this alliance is that our combined
efforts will yield multiple shots on
goal, with industry-leading pipelines of programs specifically aimed
at treating the core symptoms of
neurodevelopmental disorders.”
Members of the Seaside team
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know firsthand the challenges individuals with neurodevelopmental
disorders and their caregivers face,
Carpenter says. Seaside was founded specifically to develop diseasemodifying therapeutics for these
disorders.
“Neurodevelopmental disorders
have complex and varying etiologies, and the barrier to finding effective treatments has been a lack of
basic understanding of the molecular mechanisms underlying these
disorders,” he adds. ddn
b r i e f s
Solving the
insoluble
AMAG moves to
outsource manufacturing
LEXINGTON, Mass.—AMAG Pharmaceuticals Inc.
has announced a number of changes to its operating expenses in keeping with its focus on advancing Feraheme, its IV injection for treating iron
deficiency anemia in adult patients with chronic
kidney disease, and expanding its portfolio with
commercial-stage assets. The company expects to
eliminate 45 positions by the end of 2012, primarily in the manufacturing and development infrastructure, as it moves to an outsourced manufacturing model. In conjunction with the elimination
of its manufacturing facility, AMAG will cease production of GastroMark, having established various
agreements for the sale of the product in the
United States and European Union. External development costs will decrease as AMAG’s Phase III
broad iron deficiency anemia clinical program for
Feraheme comes to an end, and AMAG will be
reducing internal development expenses as well.
Cyprotex, Sirius Analytical
announce alliance
CHESHIRE, U.K.—Cyprotex PLC and Sirius Analytical Instruments Ltd. have announced a strategic
alliance under which Cyprotex will be able to offer
Sirius Analytical’s physiochemical property services
to its customers. Sirius Analytical’s instrumentation
is widely used for physicochemical property determination, and its latest addition, the SiriusT3, is a
fully automated system for measuring physicochemical properties using small quantities of material. Financial details were not disclosed.
“Physicochemical property determination is key
to our understanding of how a drug behaves in the
body … Sirius have an impressive record of over
20 years’ expertise in this specialist field. By partnering with Sirius, Cyprotex customers will have
access to a broader range of expert services which
complement our existing portfolio of ADME-Tox
services,” said Dr. Anthony Baxter, CEO of Cyprotex.
New forecast for CRO markets
in Indonesia, Philippines
LONDON—A
new report from GBI Research on
emerging pharmaceutical markets has recently
been published by Market Publishers Ltd. The
report, “Emerging Pharmaceutical Market in Indonesia and Philippines—100 Percent Foreign Direct
Investment in Indonesia and Extensive Insurance
Coverage in the Philippines Attract Foreign Pharma
Companies,” notes that although Indonesia and
the Philippines only account for a very small share
of the global CMO market, the two countries are
positioned to take advantage of increasing outsourcing opportunities from Western countries.
Indonesia and the Philippines recently made the
list as two of the world’s top-20 most populated
countries, and between that large patient base
and a constructive regulatory environment, the
Philippines’ CRO market is drawing global attention. Indonesia’s market, however, faces a hurdle
in the form of its drug registration procedures.
Quotient and Capsugel seek
to hasten early development
and clinical evaluation for
poorly soluble drugs
By Lloyd Dunlap
development industry.
The new company will be renamed Renaissance Pharma. As a result of the transaction,
DPT’s former parent company, DFB Pharmaceuticals, will maintain what has been
described as a “meaningful interest” in the
combined business and will provide oversight
and counsel through representation on
Renaissance’s board of directors.
“We are extremely proud of DPT’s growth
and contribution to the San Antonio community over the past 22 years,” DFB Group President and Co-Founder John W. Feik says. “This
investment by Renaissance indicates a confidence level in the local healthcare workforce
and in San Antonio, which has proven to be a
great location for the operations we have developed in the areas of pharmaceutical research,
development and manufacturing. This partnership provides the resources we need to
accelerate our long-term strategic plans, which
include maximizing our semi-solid and liquid
business in San Antonio, and achieving aggressive growth in our sterile and specialty products business in Lakewood, N.J.”
Pierre Frechette, president and CEO of
MORRISTOWN, N.J.—Capsugel, whose
2,800 hundred staffers produce more
than 180 billion capsules per year, and
Quotient Clinical, a contract research
organization (CRO) that specializes in
early-stage drug development services,
have joined forces in an effort to provide
rapid development and clinical assessment of lipid-based formulations.
Together, the companies will use
their technology and expertise to
address the drug delivery challenges of
poorly soluble molecules with limited
oral bioavailability. With up to 70 percent of the industry’s development pipeline consisting of molecules with poor
solubility, the collaboration will fasttrack the effective clinical evaluation of
lipid-based drug delivery systems in
man, while optimizing the drug product
for downstream development.
The collaboration came about, notes
Capsugel’s senior vice president of
R&D, Keith Hutchison, when Quotient
contacted his company about using
Capsugel’s CFS liquid filling and sealing
technology—a benchtop piece of equipment that delivers about 1,000 capsules
an hour—for clinical trials. In the process, Quotient and Capsugel found out
they had both worked on the same project for a third party. From there, it was
simple to proceed to the next step and
integrate Quotient’s RapidFACT realtime clinical manufacture and testing
service with Capsugel’s lipid-based formulation expertise and manufacturing
capability. As part of the collaboration,
Quotient will utilize Capsugel’s CFS
liquid capsule filling and sealing technology at its facility in Nottingham,
U.K., and will be able to access the formulation expertise in Capsugel’s Development Centre in Strasbourg, France.
Mark Egerton, managing director of
Quotient Clinical, points out that while
the collaboration will help customers
address prevalent drug delivery challenges for poorly soluble compounds
in a more effective way, it will also “further empower our RapidFACT service
by ensuring that selected drug products can be rapidly scaled-up and transitioned into downstream develop-
cdmo continued on page 29
solving continued on page 30
With the new alliance, Catalent will provide Bend Research clients with analytical/CMC, optimization and
clinical and commercial manufacturing services in a cGMP environment.
Control issues
Bend Research and Catalent
partner to provide integrated
solutions for oral controlledrelease technologies
By Jeffrey Bouley
BEND, Ore.—Late June saw Bend Research Inc.
and Somerset, N.J.-based Catalent Pharma
Solutions Inc. enter into an agreement to pro-
vide integrated solutions for pharmaceutical
companies that are seeking to develop and
manufacture specialized multiparticulate oral
controlled-release products. The team-up is
particularly focused on bringing complex
controlled-release products to market faster
and more efficiently with optimal therapeutic
and release profiles.
Catalent and Bend Research have entered
oral continued on page 29
Renaissance Pharma
acquires DPT, a CDMO
Pharma drawn to DPT’s
contract development and
manufacturing capabilities
By Lori Lesko
LAKE FOREST, Ill.—Taking industry healthcare
leaders and stockholders by surprise, Renaissance Acquisition Holdings, a portfolio company of RoundTable Healthcare Partners, has
acquired DPT Laboratories, known for its
world-class semi-solid, liquid and sterile
pharmaceutical contract development and
manufacturing capabilities (CDMO). The
business venture that some are calling a takeover underscores Renaissance’s goals to
expand and diversify.
DPT, headquartered in San Antonio, Texas,
will retain its management personnel and will
not lose jobs. The financial details of the deal,
announced July 5, were not disclosed.
Paul Dorman, former CEO of DPT, said in a
statement that the company was not planning
a sale of DPT when it first started discussions
with RoundTable about future opportunities.
The move came out of the blue because Renaissance and DPT are competitors in the drug
oral
into “a number of successful collaborations in the past,” Ian Muir, president of Catalent Pharma Solutions’
Modified Release Technologies business, tells ddn. Dr. Rod Ray, president and CEO of Bend Research,
says joint discussions between the
companies go back at least to 2009,
noting, “We had colleagues in common and attended many of the same
professional conferences, which
gave us the opportunity to learn
more about each other.”
Based on past successes together,
Muir says, discussions became more
serious in the past few months. This
more formal alliance now provides
several synergies, Muir and Ray
note, with Ray pointing out that
Bend Research provides world-class
expertise in formulation and modeling of controlled-release multiparticulate dosage forms to Catalent’s
clients, while Catalent provides
Bend Research clients with analytical/CMC, optimization and clinical
and commercial manufacturing services in a cGMP environment.
“This is the right time for this collaboration because the number of
cdmo
Renaissance Acquisition Holdings,
agrees.
“As we review investment opportunities, we look for outstanding
companies that deliver a valueadded proposition, with strong
management teams and excellent
reputations in the markets in which
they compete,” Frechette says. “As
a market leader in the contract
development and manufacturing
space, DPT’s experienced management team has established a worldclass reputation in semisolids and
liquids, as well as a sterile business
with an outstanding regulatory
track record that is poised for significant growth. Partnering with
DPT to invest in its continued
growth and success is a perfect fit
with our strategy of building companies for the long term.”
DPT’s capabilities in sterile and
non-sterile products, as well as
soon-to-be-added parenteral drug
manufacturing capabilities, were
the key motivations for the deal
from Renaissance’s perspective,
Frechette says.
Paul Johnson, group president
and COO of DPT, emphasizes that
the deal is expected to boost DPT’s
growth potential.
“Renaissance and its management team bring a depth of industry
experience, including a specific
understanding of the contract manufacturing and development space,
along with a successful history of
partnering with companies like ours
to help them grow,” Johnson says.
“This partnership provides the
resources we need to accelerate our
long-term strategic plans.” ddn
CONTRACT RESEARCH SERVICES
difficult-to-formulate compounds
in most companies’ pipelines has
never been higher, requiring the
combined skill sets of both companies,” Ray says. “In addition,
because of the intensely competitive
nature of the pharmaceutical industry, the need for improved efficiency
in bringing products to market has
never been greater. This alliance
addresses both of those issues.”
“This is the right pairing,” he
adds, “because our two firms both
specialize in controlled-release multiparticulate formulations and offer
different, but complementary, services—all of which are needed in
advancing formulations from discovery to market.”
Philosophically, both companies
fit well, Muir says, as they each
work toward the same end goal of
providing optimal solutions to customers for challenging controlledrelease products, with Catalent in
particular focused on helping the
pharmaceutical industry with compounds that are difficult to formulate and manufacture using modified release technologies.
“This alliance will provide our
customers with industry-leading
formulation scientists and innovative manufacturing technologies
across both companies to bring
more products to market in an efficient approach, from formulation to
commercialization through lifecycle
management,” Muir says.
Reportedly, Catalent and Bend
Research are developing joint operations and technology-transfer protocols to make the customer experience seamless and efficient while
leveraging the strengths of both
companies to develop better treatments for patients globally.
“Our integrated approach is
geared toward complex, multiparticulate controlled-release products,
which traditionally have presented
a high scale-up risk when they are
transferred to commercial manufacturing sites,” said Ray in the news
release about the deal. “This partnership with Catalent will provide
an efficient pathway for these medicines from early development
through commercialization.” ddn
CONTRACT RESEARCH SERVICES
Global peptide partnership
peptisyntha and peptides
international will team
up to produce researchgrade peptide apis
By lloyd dunlAp
LOUISVILLE, Ky.—Peptides
International (PI) and Peptisyntha have
entered into a global partnership for
the production of research-grade
peptide active pharmaceutical
ingredients (APIs). Customers will
benefit from access to the combined
research and manufacturing expertise of the two companies, as well as
seamless transition from research
level through commercial manufacturing, saving customers time and
cost from peptide candidate screening through preclinical and clinical
development. The collaboration
will be facilitated by a technology
transfer internal agreement.
Peptides International can pro-
duce 36 peptides in a four- to fiveday period, depending on length
and sequence, running its automated small-scale synthesizer around
the clock.
“This makes us competitive with
Asian outfits,” says PI President
and Chief Operating Officer Dr.
Michael Pennington.
In addition, Pennington notes, the
company has custom peptide synthesis expertise across a wide range
According to Peptides International President
and Chief Operating Officer Dr. Michael
Pennington, his company can produce 36
peptides in a four- to five-day period, depending
on length and sequence, running its automated
small-scale synthesizer around the clock. “This
makes us competitive with Asian outfits,” he says.
of technologies, from multi-disulfide
peptides to multistep organic synthesis. PI also offers an extensive
portfolio of building blocks and
other peptide synthesis tools.
With 25 years of experience in
peptide manufacturing, Peptisyntha, a wholly owned company of
Solvay, provides expertise from lead
optimization to commercial cGMP
manufacturing. Peptisyntha has
developed and demonstrated expertise in the design of cost-effective
peptide manufacturing processes
and in the cGMP production of
clinical and commercial peptide
APIs. Its facilities have had numerous successful U.S. Food and Drug
Administration and European
Medicines Agency inspections and
offer a full range of solid-phase,
liquid-phase and hybrid synthesis
capabilities.
One reason for heightened interest in peptide chemistry is the challenge posed by the problem of drug
delivery through the cell membrane
in order to treat and manage diseases and conditions as diverse as
HIV and constipation. The discovery of cell-penetrating peptides
represented a major breakthrough
for the transport of large-cargo molecules that may be useful in clinical
applications. ddn
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SOLVING
Continued fRoM page 28
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“We use a variety of proprietary technologies and sophisticated tools such as the Lipidex Expert System—a database of proprietary formulation data aggregated and modeled—to streamline and support all aspects of the development or re-formulation process,” Hutchison states. “We
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“We also have a deep knowledge of capsules,” Hutchinson
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ddn special report
STEM CELL RESEARCH
Fourth
Secondpart
story
of in
a multi-issue
a two-part series
series
Regenerating interest
in stem cell medicine
Stem cell technologies still hold potential to replace organs
and tissues, but initial hype has been toned down
By Randall C. Willis
W
hen the idea of embryonic stem
cells first came up about three decades
ago, conversations ran rampant about
the potential—pluripotential, if you
will—of this technology to cure all human disease and
assist us with replacement organs and tissues as those
in our aging bodies failed over time. Despite a few early
achievements, however, the hype quickly trailed off to
be replaced by disappointment and anxiety.
“If you look back 20 years, the
idea was to replace defective human
parts,” says Zami Aberman, chairman and CEO of Israel-based Pluristem Therapeutics. “A lot of promises were made, but nothing happened. There were some early successes, but a true industry didn’t
develop.”
Part of the challenge, adds Adrian Harel, CEO of BrainStorm Cell
Therapeutics in Petach-Tikva, Israel, is that companies focusing on
stem cell technologies picked therapeutic targets where they couldn’t
show an economic advantage.
“Many cell-based therapy companies have failed in the past 10 years
for two primary reasons: the lack of
a profitable/sustainable business
model despite having approved
products, and having products
which offered minimal benefits over
existing, less expensive competing
products,” Harel explains. “Given
the high cost of autologous therapy
due to the need for some type of exvivo manipulation, in addition to its
lack of scalability, the only achievable business model involves
orphan populations with no current
efficacious therapy.”
Furthermore, in places like the
United States, controversies over the
use of human embryonic stem cells
(hESCs) may have significantly
slowed commercial progress. Both
Harel and Michael Hunt, CEO of
Guildford, U.K.’s ReNeuron suggest,
however, that such controversies are
not as big a problem in other regions
of the world, and Harel is quick to
point out that Israel in particular
boasts more stem cell companies per
capita than the United States.
A new dawn
More recently, stem cell technologies—and regenerative medicine,
more broadly—have seen an
upturn in their prospects as new
stem cell sources have been identified, and both academic centers
and cell specialist companies have
changed their approaches to developing the next generation of stem
cell-based therapies.
“I see ‘stem cells’ as an umbrella
term that too broadly forms a catchall for different kinds of interventions,” says Rob Brenner, president
and CEO of AlloCure, based near
Boston. “There are distinctions
between the different cells types—
ReNeuron, based in Guildford, U.K., was founded in 1997 on the basis of Chief Scientific Officer John Sinden’s work in central nervous
system models, and applies stem cells to reinvigorate or restore tissue function lost following injury such as stroke.
“I think the
growth of ‘off-theshelf’ products is
a sign of industry
and technology
maturation.
Availability of
cells is always
going to be an
issue with
autologous
therapies. If you
want to meet mass
demands and
market growth,
you cannot be
limited by your
supply and donor
population,” says
Nissim Mashiach,
CEO of MacroCure.
of function, stem cells hold promise
for restoring that function.”
Aberman agrees: “We think it’s
important to take a step-by-step
approach, viewing cells as tiny producers of cytokine cocktails that
improve cell and tissue function,”
he says. “Without product on a shelf
and some sense of quality control,
however, it will remain hard to convince Big Pharma that there is a
business here.”
The renewed interest is reflected
in the sheer number of clinical trials
currently underway around the
world involving stem cells (see
chart, “Current Clinical Trials in
Regenerative Medicine”), in which
academic and corporate scientists
are applying stem cells to a vast
array of medical conditions.
Brenner, however, raises a warning
flag on any thoughts of taking a
grapeshot approach, and suggests
that AlloCure made sure to put the
disease before the technology.
“From the outset, our scientists
were thinking about an area of significant unmet medical need—acute
kidney injury—and tried to determine what was the best tool to interdict against this condition, which
has no FDA-approved therapies. I
think other companies approached
the problem as a tool looking for an
indication,” Brenner says.
ReNeuron followed a similar
disease-centric path to therapy
development. The company was
founded in 1997 on the basis of Chief
Scientific Officer John Sinden’s
work in central nervous system
models, and as in BrainStorm’s
case, applies stem cells to reinvigorate or restore tissue function lost
following injury such as stroke.
Regenerative medicine is also
seeing its fair share of government
investment. Despite the controversial period when the hESCs came
under tight scrutiny and outright
rejection for research funding in the
United States, the U.S. National
Institutes of Health (NIH) has consistently funded regenerative medicine and stem cell research at levels
below but in alignment with those
for major therapeutic categories
such as diabetes, neurodegenerative disorders and cardiovascular
disease (see chart, “NIH Expenditures (2008-2013) on Select Therapeutic Categories”).
Likewise, regulatory agencies
like the U.S. Food and Drug Administration (FDA) and the European
Medicines Agency (EMA) continue
to actively engage the regenerative
medicine community to facilitate
the review—and hopefully, timely
approval—of new therapies as they
are developed.
“Our recent Fast Track designation is reflective of the FDA’s understanding of the importance of our
treatment to a significant unmet
medical need,” says Brenner. “As
well, it is indicative of the FDA’s belief
that there is nothing inherently problematic or worrisome about MSCs.”
Israel-based MacroCure received
similar support from the FDA, says
Nissim Mashiach, the company’s
CEO: “We’re currently enrolling
patients in a Phase III study in the
United States with a commitment
from the FDA to speed the product
to approval if it meets its clinical
criteria,” he says.
According to ReNeuron’s Hunt,
however, simply choosing a therapeutic area where nothing else works
may not be enough to ensure your
product is supported by payors.
“We need to set the bar high in
NIH Expenditures (2008-2013) on Select Therapeutic Categories
Source: U.S. National Institutes of Health (NIH)
hESCs and mesenchymal stem cells
(MSCs), for example—much as
there are different types of protein
biologics, ranging from short peptides to antibodies.”
While not necessarily abandoning the desire to outright replace
damaged tissues—and perhaps, one
day, organs via tissue engineering—
stem cell companies have tamped
down earlier rhetoric on being “the”
solution for human disease.
“Stem cells are by no means the
ultimate panacea to human disease,”
says Harel. “In fact, they do not necessarily address the cause of the
disease, as in the case of infections
or inflammatory processes, but
rather the outcome of the disease.
“In the case of amyotrophic lateral sclerosis (ALS),” Harel notes
about an area of great interest to
BrainStorm, “where there is neuronal and muscular atrophy and loss
ddn special report
Current Clinical Trials in Regenerative Medicine
Source: Clinicaltrials.gov
our clinical trials to show meaningful efficacy,” he warns. “Is it an endpoint that will garner your product
reimbursement?”
Companies will need to be creative in how they design trials to
ensure that they provide evidence
that is compelling to all stakeholders, he adds. “It’s all well and good
to have an effective product, but if
you can’t get it reimbursed by established payors, what was the point?”
he asks.
Conversations between companies, regulators and payors are
starting to happen in the United
Kingdom, he says, and ReNeuron is
looking at the pharmacoeconomics
of what they are proposing. But it’s
still early, and never an easy sell.
“I think we really have to keep
playing the broader argument of the
need to develop treatments for
chronic conditions that are currently undertreated—something of
a ‘pay- now-or-pay-later’ approach,”
Hunt says.
Autologous vs. allogeneic
With the advent of new stem cell
sources and a better understanding
of stem cell biology, there has been
dramatic growth in the development of allogeneic products, threatening the tight grip that autologous
therapies once had on this field.
In fact, there are almost equal
numbers of clinical trials currently
underway or initiating that use
either autologous or allogeneic cell
sources (1209 vs. 1167, respectively,
for those keeping score).
“Autologous stem cells are relatively easy to harvest and can form
many different cell types,” says
BrainStorm’s Harel. “More importantly, they do not present the risk
of rejection, and have a minimal risk
of forming tumors, as opposed to
embryonic stem cells, which have a
very high risk of inducing tumors.”
He also points to the 40-year
safety record of bone marrow
transplantation.
Others, like Pluristem’s Aberman, challenge this position of
superiority for autologous systems,
pointing in particular to the various
immune-privileged cells lines that
are now available, which do not
trigger an immune reaction in the
host and therefore do not require
immunosuppression when used in
allogeneic treatments. Pluristem,
for example, relies on cells derived
from placental tissues.
Mashiach downplays the significance of tissue typing as a limitation
in allogeneic cell therapies.
“We’re using blood products that
only require a simple blood test to
match donor with host, bypassing
the typical donor-recipient issues,”
he says.
He then raises a concern about
autologous systems that is echoed
by Aberman.
“With autologous therapy,”
Mashiach says, “you’re drawing
cells from the patient himself, and
that won’t work when those cells
are damaged or non-functional.”
AlloCure’s Brenner also suggests
that some medical conditions don’t
give you the luxury of working with
autologous cell therapies.
“An autologous approach just isn’t
realistic with acute kidney injury,” he
explains. “It is an acute condition that
offers no lead time to do the scale-up
and return of cells to patients. Using
MSCs, the allogeneic approach fits
within the conventional infrastructure as the cells don’t trigger an
immune response and have powerful
regen continued on page 35
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anti-inflammatory properties.”
With regard to safety, Brenner
points out that more than 5,000
patients worldwide have been treated with MSCs.
ReNeuron’s Hunt is a bit more
pragmatic about things, seeing it as
less of an “us-versus-them” discussion, and more as an “us-and/orthem” conversation.
“We’ve tried to avoid the autologous versus allogeneic debate,” he
says. “Allogeneic makes better sense
for our area of interest, but that is
not to say that autologous doesn’t
have its place. Many companies
have made autologous much more
financially viable, so one can’t be too
proscriptive. There may even be
situations within a disease state
where patient needs will dictate the
choice between autologous and allogeneic therapies.”
Off-the-shelf
Perhaps a more dramatic impact of
the expansion in allogeneic options
(and to a lesser extent, autologous
via cord blood storage) is a significant shift in the possible business
models for cell-based therapeutics
firms from a focus on service to a
focus on product.
Because allogeneic cell lines do
not require the harvesting of tissues
from the affected patient, but rather
from a healthy donor, they afford
companies the opportunity to store
REPROGRAMMING
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Israel-based Pluristem Therapeutics developed a 3D culturing system that allows it to
“tune” cells to produce a variety of cytokine cocktails that facilitate repair in a variety of
clinical conditions.
a pill,” the better it will be with
respect to engaging pharma in partnering discussions. It will take a
bold company to make that leap, he
adds, but leap they must.
Hunt describes the ways in which
ReNeuron’s products matched Big
Pharma’s needs, breaking it down
to six criteria: Therapies targeting
diseases with significant patient
populations or subgroups; diseases
that are unaddressed by existing
drugs/biologics; off-the-shelf products rather than complex procedures (e.g., complex manipulation
or re-derivation); readily scalable
with favorable cost of goods; broad
and robust data package and identifiable mode of action; comprehensive IP position.
BrainStorm’s Harel is quick to
“Change how you process grapes
and you change the flavor of the
wine and its quality. Likewise, if you
change how you process the cells,
you change how they function and
their quality,” says Zami Aberman,
chairman and CEO of Israel-based
Pluristem Therapeutics.
them in a freezer for later use or
modification. In essence, when a
new patient shows up in a hospital,
the attending physician has the
opportunity to merely place an order
for cell-based treatment as they
would for a more traditional smallmolecule or biologic-based therapy.
“I think the growth of ‘off-theshelf’ products is a sign of industry
and technology maturation,” says
Mashiach. “Availability of cells is
always going to be an issue with
autologous therapies. If you want to
meet mass demands and market
growth, you cannot be limited by
your supply and donor population.”
And this change in model has
definitely attracted the interest of
Big Pharma as it looks to fill its
dwindling pipelines.
“We have engaged larger biopharmaceutical companies in conversation, and we get the sense that
[the off-the-shelf] approach is easier for them to accept as a better fit
for them,” says Brenner.
Hunt puts it more succinctly: The
closer you can get to “cell therapy in
remind us, however, that there may
still be limitations for these solutions
and a role for autologous therapies.
“Off-the-shelf, allogeneic cellbased therapies still require matching and immunosuppression, as is
the case with other transplants, and
will therefore never be as straightforward as drug treatment,” he
warns. “In the case of autologous
cell-based therapy such as ours,
where the patient’s own cells are
manipulated and differentiated, the
model is completely different. It’s
actually personalized medicine.”
Again, Hunt holds the middle
ground, noting that companies
developing autologous therapeutics
have come a long way in developing
relatively inexpensive and scalable
solutions, much like their allogeneic
counterparts.
A body of work
The longtime goal of regenerative
medicine has been to discover ways
to either replace endogenous tissue
functions with exogenous cells, or to
at least give the body an opportunity
to heal itself through the stimulation
and support of endogenous repair
functions. Thus, stem cell-based
therapies have been developed that
target an array of conditions.
One area that has proven to be a
success story for regenerative medicine has been wound healing,
although much of the earlier efforts
were focused on the cell-based engineering of skin replacements. Companies like Organogenesis, based in
Canton, Mass., continue to pioneer
the field of skin replacement—in this
case, with its Apligraf technology,
which is essentially skin grown in a
Petri dish.
Similarly, Columbia, Md.-based
Osiris Therapeutics has leveraged
its growing expertise in stem cell
technologies to develop Grafix skin
replacement technology, whereby
MSCs are cultured with growth factors and a natural scaffold known
as an extracellular matrix to form
newly generated skin.
MacroCure took a slightly different
route, however, when it developed its
CureXcell technology, which is currently on the market in Israel. Rather
than produce a skin replacement,
MacroCure developed a cell-based
therapy that stimulates cells within
the wound to initiate its own repair.
“We like to think of skin substitutes such as Apligraf as healing
from the outside in, whereas CureXcell is more about healing from the
inside out,” explains Mashiach.
“CureXcell is a full, systemic
approach using a cocktail of cells
harvested from whole blood, which
are injected into the wound and trigger a cascade of cellular functions
that promote angiogenesis and the
formation of new collagen.”
In CureXcell, the cells are activated to maintain their potency
before being injected into the wound
tissue, where they trigger a cascade
that first re-establishes hemostasis,
then inhibits inflammation, promotes revascularization of the tissues and finally stimulates collagen
production and wound healing.
“We’re currently enrolling
patients in a Phase III study in the
United States with a commitment
from the FDA to speed the product
to approval if it meets its clinical
criteria, and CureXcell has been
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regen continued on page 36
54780_CO03264 PSC Reprogramming DDN 1-3.indd 1
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ddn special report
regen
tested in more than 5,000 patients in Israel on
a variety of wound types,” says Mashiach.
Nerves of steel
Another area of intense interest and significant unmet medical need is the treatment of
neurological conditions, such as ALS, Parkinson’s disease (PD) and the effects of stroke.
Using an autologous approach, BrainStorm
has developed the NurOwn system to target
conditions such as ALS, PD and multiple sclerosis. MSCs from a patient’s bone marrow are
induced to produce neurotrophic factors.
These cells are then transplanted back into
the patient near the site of damage, where
they stimulate local neuronal growth and
hopefully slow or stop damage progression.
According to company CEO Adrian Hurel,
the company is currently conducting Phase I/
II safety studies in Israel in patients with both
late- and early-stage ALS, and recently entered
into a memorandum of understanding with
institutes in Massachusetts to conduct Phase
II ALS studies they hope to initiate in late 2012.
In the United Kingdom, meanwhile, ReNeuron recently initiated clinical testing (the Pilot
Investigation of Stem Cells in Stroke, or
PISCES, study) of its allogeneic neural stem cell
Muir of the University of Glasgow said, “The
data indicate that the ReN001 treatment has
a good safety profile at the doses administered
thus far. The preliminary signals of potential
functional benefit, whilst intriguing, will
require further investigation in a suitably
designed Phase II efficacy study.”
Brenner, cardiac interventions such as the use
of specific contrast agents or bypass machinery can trigger acute kidney injury (AKI).
Using MSCs derived from allogeneic bone
marrow, AlloCure induces the cells to secrete
a variety of growth factors and anti-inflammatory factors upon introduction to the damaged tissue, triggering repair through the
growth of new cells and blood vessels. In
November, the company presented findings
of a Phase I safety and efficacy trial, showing
that treatment not only lowered the incidence
of AKI in cardiac surgery patients, but also
shortened hospital stays and reduced readmission rates. A Phase II study was underway as we went to press, with results from
more than 200 patients expected in early 2014.
At its heart
Given the increasingly aging population coping
with conditions like obesity and cardiovascular
disease, this disease area has become a target
for intensive research in stem cell-based
therapies.
In July, Los Angeles-based Capricor
announced it had received FDA approval to
initiate the Phase II ALLSTAR clinical trial of
its Intensicor system in patients following large
myocardial infarctions (MIs). With Intensicor,
cardiac-derived stem cells (CDCs) are cultured
from donor hearts that could not be used for
transplantation (allogeneic) or biopsied heart
tissue from the patient (autologous), and then
reinjected into the damaged heart muscle to
stimulate cardiac regeneration.
In a similar manner, Cleveland’s Athersys
has developed the MultiStem system to treat
damage following MI, as well as other conditions. MultiStem relies on allogeneic stem
cells isolated from bone marrow or other nonembryonic tissues that are introduced to isch-
Sweet surrender
The so-called obesity epidemic has also triggered a growing problem—at least in the developed world—of diabetes, an area that is actively being explored by a number of companies.
Type 1 diabetes is an autoimmune disease
in which the insulin-producing cells in the
pancreas are specifically attacked and
destroyed. The autoimmune aspect of the condition complicates its treatment, explains
Sarah Ferber, chief scientific officer and
founder of White Plains, N.Y.-based Orgenesis, as any healthy pancreatic cells introduced
into the body would simply be destroyed.
For this reason, Orgenesis focused its
efforts on the conversion of autologous liver
cells into insulin-producing cells that could be
reimplanted in the liver to essentially replace
the missing functions of the pancreas.
“Liver is developmentally related to the
pancreas and both tissues are sensitive to glucose,” she explains. “In addition, liver has a
substantial regenerative capacity and functional redundancy.”
While an unusual approach for most cellbased therapies, there is evolutionary precedent for this diabetic multi-organ shell game.
Several organisms (e.g., eels and worms), Ferber explains, do not have a separate liver and
pancreas, but rather a single organ called the
“Without product on a shelf and some sense of
quality control, it will remain hard to convince
Big Pharma that there is a business here.”
Zami Aberman, chairman and CEO of Pluristem Therapeutics
technology in patients disabled by stroke. Starting with a fetal progenitor source back in 2003,
the company screened a variety of immortalized cell lines to identify potential therapeutic
candidates, cells targeting stroke-related damage being the strongest initial candidate.
In a June release describing early data from
the first patients in the PISCES study, principal investigator and neuroscientist Keith
emic regions of the heart through a catheter.
The company’s Phase I study, published earlier this year, showed significant improvement in cardiac function following MI without any safety concerns.
Cardiovascular disease doesn’t just impact
the heart, however, as events involving the
heart can have significant impact elsewhere in
the body, such as the kidneys. As described by
Discovery
Drug Disco
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Manchester Central
The rest of the story
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Innovation Zone - New companies showing their latest technologies, make sure you visit them.
Should your company be in the Innovation Zone? If so apply now.
Exhibition Trade Show - Around 100 companies on show : book your stand at www.elrig.org
hepatopancreas. The company is still in the
preclinical proof-of-concept phase, but has
initiated conversations with regulators about
proceeding to clinical trial.
Like cardiac disease, diabetes does not simply limit its effects to the blood sugar and
energy levels, but can also have secondary
impacts, including a condition known as
peripheral artery disease (PAD) where blood
flow is blocked (often in the legs) and tissue
damage can occur.
Using MSC-like stem cells derived from
placenta, Pluristem developed a 3D culturing
system that allows it to “tune” cells to produce
a variety of cytokine cocktails that would
facilitate repair in a variety of clinical conditions, including PAD. Aberman draws a parallel with the wine industry: “Change how
you process grapes, and you change the flavor
of the wine and its quality. Likewise, if you
change how you process the cells, you change
how they function and their quality.”
At the Biotechnology Industry Organization annual conference in June, the company
introduced the results of preclinical studies
in the use of the PLX system via intramuscular (IM) injection rather than through intravenous injection or direct application to the
site of injury. According to Aberman, the ability to perform IM administration has significant market implications that potentially
broaden not only to what diseases the product
can be applied, but also who can apply them
and how often.
In July, the company announced a partnership with CPC Clinical Research to initiate
Phase II studies of the PLX system in PAD,
but perhaps the most dramatic moment came
back in May, when the company announced
the results of its compassionate use of PLX in
a young girl who failed two bone marrow
transplants and was expected to die.
Within 10 days of the second and last injection of PLX, the patient’s hematological patterns
improved dramatically, and subsequent biopsies showed that cells from both bone marrow
transplants were finally growing and maturing.
After nine months, the patient was discharged
from the hospital and is doing well.
“The physician treating the girl was in the
same hospital where we had established our
acute radiation models to develop PLX and
he asked for compassionate use,” explains
Aberman. “You can do a lot in animals that
may not work in humans. This worked.”
Other areas for which cell-based therapies are
being developed by these and other companies include: Autoimmune conditions such
as Crohn’s disease and rheumatoid arthritis
(e.g., Osiris, TiGenix, Mesoblast, TxCell);
musculoskeletal conditions such as cartilage
regeneration (e.g., Pluristem, Histogenics,
Azellon Cell Therapeutics); ocular conditions
such as AMD and retinopathy (e.g., International Stem Cell, EyeCyte, Advanced Cell
Technology); and oncological conditions such
as neutropenia (e.g., Cellerant Therapeutics,
Gamida Cell Therapy Technologies).
Lessons learned?
Whether licking their wounds and dusting
themselves off, or learning from the lessons of
others who have fallen before them, the latest
crop of regenerative medicine companies and
scientists seem to be taking a much more
methodical and deliberate approach to developing the next generation of cell-based therapies.
It will take some time and patience, however, to
see if those lessons have become ingrained. ddn
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solutions that offer sample preparation and enrichment in a single integrated workflow. The kits
support the industry’s lowest DNA sample input
requirements (50 ng) and enable a range of studies from small gene panels to full human exomes.
The kits’ workflow can be performed in less than
three hours, with high enrichment rates and no
need for mechanical DNA fragmentation. Nextera
Exome Enrichment kits provide comprehensive
coverage, with greater than 62 Mb of coding
regions and untranslated regions.
Illumina Inc.
(858) 202-4500
www.illumina.com
Increased Y-STR loci detection
Promega Corp.
Promega announces the release of the PowerPlex
Y23 System, a rapid human identification Y-Short
Tandem Repeat assay for forensic casework, with
applications in paternity testing and offender
databasing. The system detects more Y-STR loci
than current systems, with thermal cycling time
nearly halved, and rapid cycling co-amplifies 23
Y-STR loci for maximum discrimination. In alpha
tests, most users could detect profiles with as
little as 32.5pg of DNA, and complete profiles
were detected with 62pg of male DNA in the presence of 400ng of female DNA.
Promega Corp.
(800) 356-9526
www.promega.com
www.affymetrix.com
www.aldrichmarketselect.com
www.amriglobal.com
www. photophysics.com
www.atcc.org
www.biotek.com
www.healthtech.com
www.elsevier.com
www.millipore.com
www.eppendorf.com
www.gilson.com
www.hamiltonrobotics.com
www.invitrogen.com
www.mirusbio.com
www.moleculardevices.com
www.origene.com
www.panasonic.com/biomedical
www.RnDSystems.com
www.roche-applied-science.com
www.ssi.shimadzu.com
www.slas.org
www.waters.com
minimized cross-interference for oxygen measurements, with redesigned, independent gas inlets
and automatic compensation for changes in the
atmospheric partial pressure of CO2 thanks to a
unique altitude correction function. The Infinite
200 PRO features cell biology-oriented functions
such as Optimal Cell Reading, linear and orbital
shaking, advanced temperature control and automated Z-focusing.
Tecan
+41 44 922 81 11
www.tecan.com
Supply portfolio for increased
performance, productivity
Agilent Technologies Inc.
Agilent Technologies Inc. introduces CrossLab
HPLC supplies and services to help improve
performance and productivity in non-Agilent instrumentation while reducing administrative burdens
with a single-source solution. The supply portfolio
includes detector lamps, valve and pump supplies,
capillaries and fittings, HPLC autosampler syringes, vials and closures, well plates and sealing
mats, with more to follow, and the supplies are
manufactured to work seamlessly with a wide
variety of non-Agilent instruments, including HPLCs
from Waters, Shimadzu and Dionex.
Agilent Technologies Inc.
(877) 424-4536
www.agilent.com
Purified proteins
from HEK293 cells
OriGene
Simultaneous O2,
CO2 concentration control
Tecan
Tecan announces its updated Gas Control Module
(GCM) for the Infinite 200 PRO multimode reader, which now provides simultaneous control of
O2 and CO2 concentrations. The updated system
provides increased measurement accuracy and
OriGene is now offering more than 7,000 full-length
human proteins purified from HEK293 cells, providing better preservation of the characteristics
of the native human proteins and offering better
material for assay development. Validated by
Western blot and mass spectrometry, the proteins
offer more than 80-percent purity through affinity
purification, with applications in protein-protein
interaction, as positive controls in ELISA and other
antibody assays and in in-vitro biochemical assays
and cell-based functional assays.
OriGene
(888) 267-4436
www.origene.com
facts & Figures
Report calls Europe stem cell research
tools market ‘a hype and a hope’
I
n spite of a positive hope for the stem cell
European Stem Cell Research Tools Market Outlook (2010)
research industry, there remains a fear of the production of embryonic stem cell-based tools, and particularly in Europe, stiff patent laws with regard to some
stem cell treatments may cause the commercialization and
production of human stem cell-based technologies to face
a fallback. In addition, researchers in academic areas may
elect to pursue projects with lesser career uncertainties until
the dust settles in stem cell-oriented topics, according to a
recent assessment of the European stem cell research tools
market by business consulting firm Frost & Sullivan.
According to the report, “Strategic Analysis of the European Stem Cell Research Tools
Market: A Hype and a Hope,” public perception and funding is seen as a disastrous challenge.
Scientists fear the disruption of European research collaboration and other stem cell communities if the trend continues, and companies may invest in development of technologies in
other countries that have a better scope.
Technologies typically employed in stem cell research and examined by the report include
bioimaging, cell biology, immunochemical, molecular biology and protein biochemistry tools.
The total stem cell research tools market composed of these five segments totaled $131.8 million
in 2010, and is projected to reach $322 million in 2017, according to Frost & Sullivan.
In particular, cell biology tools for stem cell research will experience a tremendous growth
rate in upcoming years. Due to liberalized funding in certain government programs, there will
be an increase in the trend for the uptake of stem cell experiments.
“Stem cells will definitely be seen as a curative tool for many diseases,” Frost & Sullivan
concludes, “but the biased opinion on their use is lowering the potential there by delaying the
penetration of success.”
Key companies assessed in the report include BD Biosciences, Bio-Rad, EMD Millipore, Life
Technologies, Qiagen, R&D Systems, Sigma Aldrich, Stem Cell Technologies and Thermo Fisher
Scientific, “although dozens of other suppliers exist,” Frost & Sullivan notes. ddn
European Stem Cell Research Tools Market,
Segment Life Cycle Analysis (2010)
European Stem Cell Research Tools Market, Revenues (2010)
European Stem Cell Research Tools,
Revenue Forecast (2010–2017)
European Stem Cell Research Tools Market, Revenues (2017)
Drug Discovery News (USPS 024-504) is published monthly by Old River Publications LLC, 19035 Old Detroit Road, Suite 203, Rocky River, OH 44116; 440-331-6600. Periodical postage paid at Cleveland, Ohio and additional mailing
offices. Publisher assumes no responsibility for unsolicited material or prices quoted in the magazine. Contributors are responsible for proprietary classified information. ©2012 by Old River Publications. All rights reserved. Reproduction,
in whole or in part, without written permission of the publisher is expressly prohibited. Back issues, when available, cost $7 each within the past 12 months; $12 each prior to the past 12 months. Back orders must be paid in advance
by check. Drug Discovery News is distributed without charge in North America to qualified drug discovery research professionals. Paid subscriptions to those not qualified cost $65 annually to the U.S. and Canada and $150 to all other
countries. All payments must be made in U.S. funds drawn on a U.S. bank. Publications mail agreement no. 41401058 return undeliverable Canadian addresses to PO Box 503, RPO West Beaver Creek, Richmond Hill, ON L4B 4R6.
For subscription services, including subscription information, please call 215-785-5196. POSTMASTER: Send address changes to Drug Discovery News, PO Box 3100, Langhorne, PA 19047-8800.
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