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NATIONAL BREAST CANCER AWARENESS MONTH
PHARMA, BIOTECH
DISCOVERY6
RESEARCH & DEVELOPMENT
12
PRECLINICAL18
CLINICAL TRIALS
29
DIAGNOSTICS35
CONTRACT SERVICES
38
BUSINESS & GOVERNMENT POLICY
41
TOOLS & TECHNOLOGY
Two advances in sequencing prep...................................16
Muddy waters for cancer detection?..............................35
A pan-Pacific partnership..................................................36
Toward a total solution........................................................41
On the cutting edge.............................................................42
FINANCE/MARKETS3
EDITORIAL/COMMENTARY10
PRODUCTS & SERVICES
46
DIAGNOSTICS
SPECIAL REPORT:
22
Non-invasion of
the body snatchers
To avoid tissue biopsy, researchers
are turning to diagnostic biofluids
OCTOBER 2015 : VOLUME 11 : NUMBER 10
PUBLISHED SINCE 2005
10.15
The XF factor
California’s Agilent to
acquire Massachusettsbased Seahorse
Bioscience and its
assay kits for measuring
cell metabolism
for $235 million
BY LORI LESKO
SANTA CLARA, Calif.—Striving to be first
in the analytical labs market and targeted
clinical research field while expanding
future pharma offerings, biotech Agilent
Technologies Inc. has signed an agreement
for the acquisition of Seahorse Bioscience and its assay kits for measuring cell
metabolism—including its proprietary XF
Technology—for $235 million. The deal is
expected to be finalized on Nov. 1.
The use of cell metabolism in research
is rapidly accelerating as the links between
mitochondrial function and disease are
increasingly revealed, the companies note,
and Seahorse Bioscience’s technology enables
researchers to better understand cell health,
function and signaling and how the cell may
be impacted by the introduction of a specific
drug—also providing real-time kinetics to
unlock essential cellular bioenergetics data.
But it’s Seahorse’s XF technology which
gives scientists faster, better and more
accurate measurements of real-time
cellular bioenergetics. By measuring the
two major energy producing pathways of
the cell simultaneously, mitochondrial
respiration and glycolysis, scientists get the
most physiologically relevant bioenergetic
assay available, resulting in a better overall
view of metabolism, according to Seahorse.
Its XF technology also measures fatty acid
CREDIT: SEAHORSE BIOSCIENCE
WHAT’S INSIDE
LIFE SCIENCE
A Seahorse Biosciences researcher works at
an XFp Analyzer in the laboratory. The
company’s XF technology was a key draw for
Agilent in moving toward an acquisition of
the company.
SEAHORSE CONTINUED ON PAGE 43
“The acquisition of Seahorse Bioscience is one of
Agilent’s largest and important to the company,
but we have made two larger, previous
acquisitions that were critical to the evolution of
Agilent as a company focused on life sciences,
diagnostics and the applied chemicals market.”
Michele Drake, corporate media relations manager for Agilent
Taking time and money out of clinical trials
ICON and IBM plan to
revolutionize clinical
trial feasibility, patient
recruitment and study
start-up timelines
IBM, the Armonk, N.Y., headquarters of
which are pictured here, is teaming with
ICON to help reduce the time and costs of
drug development by better connecting
patients to relevant clinical trials.
BY LLOYD DUNLAP
ebrated its 25th anniversary as a global provider of drug development solutions and services to the pharmaceutical, biotechnology
and medical device industries, is partnering with IBM to help reduce the time
and costs of drug development, while also
offering patients enhanced quality of care by
connecting them to relevant clinical trials.
ICON will tap Watson’s cognitive computing power to help automate the cumbersome process of identifying patients who
meet the criteria for a clinical trial, and to
analyze protocols to assess trial feasibility
and identify optimal trial sites.
ICON’s chief operating officer, Dr. Steve
Cutler, says it’s too early to estimate what
reductions in time and cost might be
achieved, but he expects them to be “substantial” and says that the pilot program “will
tell us much more.”
Initially, ICON is applying Watson Clini-
CREDIT: IBM
DUBLIN, Ireland—ICON plc, which just cel-
cal Trial Matching to its breast, lung, colon
and rectal cancer trials. The solution enables
ICON to advise sponsors how many patients
match their trial criteria, where they are located and how they will recruit them. IBM’s
Watson Health Cloud will facilitate access
to de-identified patient data, including 50
million patient records contained in the
data set from Explorys, which IBM acquired
in April. At the same time, ICON enhances
IBM Watson’s capabilities by providing
expertise into clinical trial protocols and
clinical operations.
Cutler notes that Watson’s cognitive learning skills will allow it to recognize oncological terms and data and to read unstructured
data. “Watson can also use OCR technology
to read doctor’s notes and apply inclusion/
exclusion criteria,” he observes. “Doctors can
make decisions while the patient is in front
of him or her.”
The cost and time involved in clinical
trials is considerable. More than $1.3 billion is spent on patient recruitment by drug
developers each year, and yet fewer than 5
percent of cancer patients participate in a
clinical trial. It also typically takes six to 12
months to start up a global Phase 3 drug trial
and another 12 months to enroll the required
number of patients.
Watson, it is hoped, will expedite the
process. Watson Health Cloud contains records from nearly 100 million patients coming
from multiple healthcare providers. It draws
on a wide variety of data about each patient,
including symptoms, genomic data, test
results, diagnoses, treatments and outcomes.
Cutler adds that “Recruiting the required
number of patients for clinical trials is a
constant challenge for our customers and
can represent more than 30 percent of total
study costs. By applying IBM Watson to our
clinical trials, we have the potential to revolutionize clinical trial feasibility, patient
recruitment and study start-up timelines,
which will help our customers take significant time and cost from their development
programs. Together with IBM, we are also
providing a better and faster way to connect
patients with clinical trials that are most
relevant to them. [This] announcement is
an excellent example of disruptive innovation and represents ICON and IBM’s shared
TRIALS CONTINUED ON PAGE 32
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and its subsidiaries around the world. © Copyright 2015. Covance Inc.
FINANCE
Zephyr closes $17.5-million Series C round led by Google Ventures
For more information, visit www.DDN-News.com
SAN FRANCISCO—This summer
saw Zephyr Health, an insights-asa-service company for the healthcare industry, announce that it had
closed a $17.5-million funding round
led by Google Ventures. Current
investors Kleiner Perkins Caufield
& Byers (KPCB) and Icon Ventures
also participated in the round.
Zephyr Health has received a total
of $33.5 million in funding to date.
“At Google Ventures, we look for
companies that work at the intersection of data science and healthcare,”
said Blake Byers, general partner at
Google Ventures. “Zephyr Health is
at the forefront of healthcare analytics. Zephyr integrates thousands
of public and private data sources
Thrive Bioscience
raises $4-million
seed round
BEVERLY, Mass.—Recently, Thrive
Bioscience announced that it had
closed a $4-million round of seed
financing from angel groups, strategic partners and industry veterans
to accelerate commercialization
of “previously unavailable solutions that advance drug discovery,
research and delivery of new therapies by improving one of the most
important research processes—cell
culture.”
Investors in Thrive’s first round
of financing include Life Science
Angels, SideCar Angels, Triple
Ring Technologies and Optikos
Corp. Also among the financiers
were numerous accomplished
industry veterans and prominent
angels, including Guy Broadbent
of Argotec, former CEO of Xcellerex and former president of
Thermo Fisher’s Laboratory Products Group; Andrew Egendorf, an
inventor and intellectual property
expert; Michael Finney of Finney
Capital, founder of MJ Research
and former CEO of Vaxart; Douglas Hansen of Resonant Capital
and former president of Redwood
Trust; Jerry Karabelas of Care Capital and former CEO of worldwide
pharmaceuticals at Novartis; Stan
Lapidus of SynapDx and founder of
Cytyc and Exact Laboratories; Norman Sorensen, formerly of Principal Financial Group; and Willard
Umphrey of U.S. Boston Capital.
Regarding the use of proceeds,
Thomas Forest Farb, president
and co-founder of Thrive, stated,
“This $4-million financing, and the
industry expertise of our investors,
supports Thrive’s experienced team
in the development of its extensive
product family, establishment of
research collaborations, building
a significant intellectual property
estate and the launch of the Cell
Culture Standardization Consortium. Thrive’s instruments will take
cell culture from the analog to the
digital age and enable better, faster
and more cost-effective research.” n
to provide deep, predictive insights
that enable customers to accelerate
time to market for drugs, diagnostics and devices.”
On average, it costs pharmaceutical companies between $1.5
billion and $2.4 billion to bring a
new therapy to market, with only
33 percent of those products meeting their initial sales goals, Zephyr
noted, and its customers, including
Fortune 100 Genentech, Gilead,
Medtronic, Onyx and Amgen, use
the company’s Illuminate solution
to improve business results across
the product lifecycle. The solution’s proprietary algorithms link
data from thousands of disconnected sources to generate predictive insights that power precise and
confident performance across the
product lifecycle.
“At Zephyr Health we have a
strong team and proven solutions
OCTOBER 2015 | | DDNEWS 3
for leading pharmaceutical and
medical device companies,” said
William King, founder and CEO
of Zephyr Health. “With the support of Google Ventures, along with
KPCB and Icon, we look forward
to a collaborative partnership that
will allow us to tap into their vast
resources of knowledge and experience, helping us to further expand
our business with new products
and in new areas.”
Founded in 2011, Zephyr Health
is “harnessing the power of global
healthcare data for precise and
confident product lifecycle performance for biopharmaceutical
and medical device companies.”
The company’s services span the
range from clinical trials to market strategy and sales. Although
Zephyr Health is headquartered in
San Francisco, it also has offices in
London and Pune, India. n
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MARKETS
4 DDNEWS | | OCTOBER 2015
PHARMACEUTICAL AND
BIOTECH MARKET INDICES
Long-acting growth hormone
deficiency treatments will
boost market growth from 2017
LONDON—The global market for growth hormone deficiency (GHD) treatment
will rise in value from $1.26 billion in 2014 to reach approximately $1.88 billion
by 2024, representing a moderate compound annual growth rate (CAGR) of 4.08
percent, according to research and consulting firm GlobalData.
The company reports that the increase, which will occur across the seven major
countries of the United States, France, Germany, Italy, Spain, United Kingdom
and Japan, will be primarily driven by the launch of long-acting growth hormone
biobetters, which are expected to begin entering the market in 2017.
Dr. Lakshmi Dharmarajan, GlobalData’s senior analyst covering cardiovascular and metabolic disorders, says the less-frequent dosing schedules of these
drugs will be attractive to patients, offering improved compliance and adherence
outcomes.
“According to key opinion leaders interviewed by GlobalData, patient compliance
with daily growth hormone drugs has been a long-standing issue in the GHD treatment landscape, and it remains the greatest unmet need,” says Dharmarajan. “As a
consequence, pharmaceutical companies are focusing heavily on developing easier
delivery options for patients, leading to therapies that can be administered weekly
or biweekly. Indeed, nine of the 12 drugs currently in development for GHD are
long-acting growth hormone biobetters.”
The analyst adds that many patients who currently refuse to take their daily
growth hormone injections are expected to opt for the long-acting drugs once they
become available, which will begin to increase the drug treatment rate.
GlobalData forecasts that the global sales for the daily recombinant growth hormone drugs will decline at a negative CAGR of 5.95 percent, from $1.26 billion in
2014 to $684 million by 2024. However, global sales for the long-acting growth
hormone drugs are expected to reach around $1.2 billion by the end of the forecast
period.
“While physicians will initially restrict use of the biobetters in cancer survivors,
due to fear of the hormones’ lingering effects in this patient population, the overall
prospects for long-acting growth hormone therapies are very promising,” Dharmarajan concludes. n
Pharmaceutical Index
497
17/Oct
and Science business of Thomson Reuters
recently announced the release of the
2015 CMR Pharmaceutical R&D Factbook,
which finds, among other things, that
despite concerns around declines in R&D,
there will be a surge in global pharma sales.
Specifically, 2014’s $1-trillion milestone is
forecast by the firm to reach $1.3 trillion
by 2018. The report also notes a positive
shift in new molecular entities (NMEs),
with 46 launches in 2014—the highest in
over a decade.
Among the key findings:
Diversification increases NME launches: One third of 2014 launches were for
rare indications, mainly within the anticancer realm. More than 65 percent were
specialty drugs for the treatment of cancer,
hepatitis C virus and HIV.
■■
P
532
14/Nov
12/Dec
151
99
17/Oct
Anticancer dominates: Oncology
development continues to attract the highest amount of investments across all therapeutic areas, with the majority of recent
launches receiving orphan drug status from
regulatory authorities.
Increase in failing fast and cheaply: Phase 3 pipeline volumes are steadily
growing due to the improved ability to “fail
fast and cheaply,” increasing the speed of
potentially successful compounds through
development.
“This is an extraordinary year for pharma,” said Basil Moftah, president of Thomson Reuters IP & Science. “Not only do the
critical insights provided by the Factbook
challenge negative perceptions, but it demonstrates this industry’s continued commitment
to creating and employing innovative solutions to tackle its largest hurdles.” n
L
Neothetics reports Q2 2015
SAN DIEGO—Neothetics Inc., a clinical-stage specialty pharmaceuti-
cal company developing therapeutics for the aesthetic market,
recently reported financial results and business progress for the
second quarter of 2015.
“We remain on track for reporting topline results from our pivotal U.S. Phase 3 trials later this year,” said George Mahaffey,
president and CEO of Neothetics. “There is clearly high demand
for new, safe and effective FDA-approved drug options in the rapidly growing non-invasive body contouring market. If approved,
LIPO-202 will be the first drug approved for reduction of central
abdominal bulging.”
Research and development expenses for the second quarter of
2015 were $7.5 million, compared to $900,000 for the same quar-
I
C
C O
16/Jan
13/Feb
13/Mar
582
587
580
17/Apr
15/May
17/Jun
107
106
14/Nov
12/Dec
204
203
202
205
181
186
111
111
112
116
118
116
16/Jan
13/Feb
13/Mar
17/Apr
15/May
17/Jun
171
163
602
593
16/Jul
14/Aug
556
15/Sep
MINI-BIOTECH
221
202
121
118
16/Jul
14/Aug
200
111
15/Sep
MINI-PHARMA
SOURCE: NYSE ARCA
Biotechnology Index 4073
■■
B
560
Mini-pharma and Mini-biotech Indices
■■
U
557
SOURCE: NYSE ARCA
Pharma sales to grow beyond $1 trillion
PHILADELPHIA—The Intellectual Property
535
553
3018
17/Oct
3254
14/Nov
3421
12/Dec
3523
16/Jan
4413
4056
4039
4091
17/Apr
15/May
17/Jun
4030
4001
14/Aug
15/Sep
3715
13/Feb 13/Mar
16/Jul
SOURCE: NYSE ARCA
M
P A
N
Y
ter in 2014. R&D expenses for the first six months of 2015 were
$12.2 million, compared to $2.3 million in the six month period
ended June 30, 2014.
SYGNIS reports on first half of 2015
MADRID, Spain & HEIDELBERG, Germany—SYGNIS
AG this summer
reported results for the first six months ended June 30, 2015. During this period, revenues increased by 22 percent to €196,000
compared to the same period in 2014, though “revenues do not
reflect real sales of kits adequately as kits were sold with big
discounts in the market launch phase,” the company notes. Due to
the expansion of production of these kits, direct selling activities
and special one-off effects as a result of additional restructuring
measures, operating expenses increased to €2.07 million. As of
N
E
W
S
June 30, cash and cash equivalents were €1.28 million and total
short-term assets were €1.76 million.
Ablynx announces half-year results
GHENT, Belgium—Ablynx recently announced its business update
and results for the first six months of 2015, with CEO Dr. Edwin
Moses noting, “We have made substantial progress on all fronts,
in our own fully owned programs and in our partnerships with
leading pharmaceutical companies. In our later-stage clinical
pipeline, we are now running four Phase 2 studies and will be
shortly commencing the Phase 3 study with our wholly owned
anti-vWF Nanobody, caplacizumab.”
The company anticipates increasing staff by about 10 percent,
to 350 people, during 2015. n
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DISCOVERY
CAMBRIDGE, U.K.—A research collaboration was
recently announced between Horizon Discovery
Group plc and Redx Pharma plc focused on progressing Redx’s novel pan-RAF inhibitor program,
for out-licensing in oncology indications, including
colorectal cancer. Horizon will use its proprietary
gene editing, cell line and drug discovery technology platforms to explore the mode of action for
the inhibitors and support Redx in its efforts to
move the compounds toward partnering. Though
no financial details were disclosed, Horizon and
Redx will bear collaboration costs proportionate
to their respective research activities. Should a
program asset be partnered with a pharmaceutical company, it is expected to deliver a material
return on Horizon’s investment from any upfront
payment, a share of future milestones and a share
of future product royalties.
Immatics US Inc.
launches in Houston
TUEBINGEN, Germany—Immatics Biotechnologies
GmbH and The University of Texas MD Anderson
Cancer Center in Houston have opened the doors
to Immatics US Inc., a new company focused on
becoming a global leader in adoptive cellular
therapies (ACT) for the treatment of a variety of
cancers. Immatics US has secured a first funding
round of more than $60 million, with more than $40
million committed by Immatics Biotechnologies
and $19.7 million by a recent grant from the Cancer
Prevention and Research Institute of Texas. The
new company will be advancing three different
ACT approaches for treating tumors with high
unmet medical needs, with the first of those
expected to enter the clinic next year.
“Our ongoing efforts to provide the most
innovative therapies to our patients are due,
in part, to collaborations both in academia and
industry,” said Dr. Ronald DePinho, president of
MD Anderson. “It is only through working with
other leaders in cancer science will we provide
the solutions of tomorrow.”
IN THIS SECTION
Expansion/Funding
Immatics US Inc. launches in Houston...... 6
Obesity/Diabetes
Genetic trigger for obesity discovered...... 6
Oncology
Cancer answers in the South Pacific......... 7
Horizon, Redx to advance
pan-RAF inhibitors..................................... 6
MorphoSys and Immatics
ally in immuno-oncology field................... 6
Oncology/
Neurodegnerative/Liver
Discovery boom in Southern California..... 8
MorphoSys and Immatics ally
in immuno-oncology field
Collaboration aims to
develop novel antibody-based
therapies targeting tumorassociated peptides derived
from intracellular proteins
In addition to announcing
an oncology discoveryrelated collaboration with
Immatics, MorphoSys also
recently provided updated
clinical data for its
proprietary drug candidate
MOR202, a fully human
HuCAL antibody targeting
CD38, a highly expressed
and validated target in
multiple myeloma. Pictured
here is a MorphoSys
scientist working with a
HuCAL antibody.
BY MEL J. YEATES
PLANEGG, Germany— MorphoSys AG
and Tübingen, Germany-based Immatics
Biotechnologies GmbH have announced
a strategic alliance to generate novel
antibody-based therapeutics against multiple proprietary cancer antigens recognized
by T cells. The collaboration agreement
provides MorphoSys with access to several proprietary tumor-associated peptides
(TUMAPs) discovered using Immatics’
XPRESIDENT platform, with a goal to
develop novel antibody-based therapeutics
against these targets in a number of solid
and hematological cancers. XPRESIDENT
enables access to novel antibody targets
associated with proteins present inside
cancer cells.
In return, Immatics will be provided with
MorphoSys’ Ylanthia antibodies against a
number of its TUMAPs, with proprietary
development rights. The companies will pay
each other milestones based on their respective development progress as well as royalties
on marketed products. Financial details of
the agreement were not disclosed.
“We are delighted to join forces with
Immatics, a world leader in discovering truly
TUMAP CONTINUED ON PAGE 9
Genetic trigger for obesity discovered
South Australian
researchers find
unexpected potential
in MNK gene
BY ZACK ANCHORS
ADELAIDE, Australia— Australian scienti-
sts have discovered that a gene previously
thought to play a benign role in humans is
actually a major trigger for obesity and type
2 diabetes. Researchers are optimistic that
their new understanding of the gene known
as MNK could lead to new drugs that target
the gene and prevent or treat two disorders,
which together affect billions of people
and pose major public health challenges
throughout the world.
Studies at the South Australian Health
and Medical Research Institute (SAHMRI)
compared mice missing the MNK gene with
normal mice that had the gene, which is
commonly found in livers, fatty tissue and
muscles. Both groups of mice were fed a
high-fat diet and the two groups reacted
very differently. Among the mice with MNK,
researchers observed high levels of body fat,
diabetes and inflammation of fat tissue.
The mice without MNK were free of these
characteristics, which are all associated with
CREDIT: STACY MITCHELL
Horizon, Redx to advance
pan-RAF inhibitors
CREDIT: MOPHOSYS
BR IEFS
Australian scientists at the South Australian Health and Medical Research Institute compared
mice missing the MNK gene with normal mice that had the gene and found an unexpected link
between the gene and obesity/diabetes.
obesity in both mice and humans.
SAHMRI professor Chris Proud, the lead
researcher of the studies, said that his team
still needs to gain a fuller understanding of
the mechanism through which MNK affects
weight gain and obesity. They believe,
however, that MNK is directly related to the
inflammation of fat tissue that is typically
associated with obesity. Such inflammation
is typically a root cause of the other adverse
effects that stem from obesity, including
cardiovascular disease and diabetes. In the
case of diabetes, inflammation interferes
with the normal action of insulin in the body.
“We’re interested in whether MNK plays
a role in creating new fat cells, or expanding fat cells that already exist,” Proud noted
in a statement released by SAHMRI. “We’re
conducting more experiments with mice and
fat cells in culture for quicker progress.”
Proud says his team of researchers began
to study MNK after noticing particularly high
levels of MNK in fat cells and in liver and
TRIGGER CONTINUED ON PAGE 8
DISCOVERY
Cancer answers in the South Pacific
BY ILENE SCHNEIDER
ADELAIDE, South Australia—An Australian
university has teamed up with a leading
Chinese pharmaceutical company to
develop new cancer treatments. Yabao
Pharmaceutical Co. Inc., founded in 1978,
is a specialty pharmaceutical company with
fully integrated technology development,
product development, manufacturing
and commercialization capabilities, with
headquarters in the Shanxi province of
China.
Yabao and the University of South
Australia (UniSA) will collaborate on targeted cancer therapeutics. The collaboration
will establish what they call “a true joint
“We will only discover drug candidates that
have great potential for China and globally.
Yabao will have all China market rights,
while UniSA retains rights outside of China,”
says Yabao Pharmaceutical’s president of
research and development, Dr. Peng Wang,
of a collaboration recently forged between
his company and the University of South
Australia.
drug discovery lab,” which is co-funded
and co-led by both sides, according to news
releases from both parties.
Under the terms of the agreement, the
university will identify drug candidates
in the co-funded laboratory, which will be
led by Dr. Shudong Wang, a professor at
UniSA. Yabao Pharmaceuticals will fund
the drug discovery and development in
exchange for the exclusive right to develop
and commercialize the drug candidates in
China. The University of South Australia will
retain rights in all other markets.
Yabao Pharmaceutical’s president of
research and development, Dr. Peng Wang,
says Yabao seeks to build relationships with
organizations that have innovative programs
that complement the company’s development
and commercial capabilities, adding, “We are
thrilled to have the opportunity to work with
the University of South Australia’s highly
regarded scientists and laboratories to jointly
find a way to develop important new treatments for cancer patients.”
According to Peng Wang, who is also
CEO and chief scientific officer of Suzhou
In a recent deal formed
with China’s Yabao
Pharmaceuticals, the
University of South
Australia (pictured here)
will identify potential
anticancer drug
candidates in a
co-funded laboratory.
CREDIT: UNIVERSITY OF SOUTH AUSTRALIA
Yabao Pharmaceuticals
and University of
South Australia
collaborate on joint drug
discovery laboratory
Yabao Pharmaceutical R&D Co.—a start-up
focusing on innovative R&D in China for the
world through international collaboration—
the two parties will plan jointly and conduct
appropriate studies on small-molecule, targeted oncology drugs. Wang also helped in the
establishment of several collaboration partnerships with Eli Lilly and Co., Bristol-Myers
Squibb, Merck, OSI Pharmaceuticals, Primary Peptides (Canada) and several academic
organizations.
The initial term of the agreement is
three years, which can be extended, he tells
DDNews, adding: “We will only discover
drug candidates that have great potential
for China and globally. Yabao will have all
China market rights, while UniSA retains
rights outside of China.”
Head of the Centre for Drug Discovery
and Development at the University of South
Australia Prof. Shudong Wang is looking
forward to a productive collaboration with
Yabao, which brings a strong commitment
to the Centre’s drug discovery program, and
she says, “The financial resources resulting
from this agreement will help to rapidly
advance our drug discovery towards clinical
development, a goal we all share.”
“We are developing a new type of targeted cancer therapeutic,” Shudong Wang
tells DDNews. “The drug target is an enzyme
that is highly expressed in the majority of
colorectal cancers. Inhibition of this kinase
by our drug molecule compound suppresses
proliferation in colon cancer cells and
causes cancer cell death. Another very
exciting perspective of this program is to
be able to address the complex nature of
cancer immunology. It raises the hope of
enhancing clinical efficacy and outcome.”
The two parties note that colorectal cancer (CRC) is the second most commonly
diagnosed form of cancer. In 2010, approximately 1.6 million individuals were affect-
ed by CRC. Mortality rates are set to rise,
despite the positive impact of screening on
the early identification of the disease. The
global cancer market in 2010 was valued at
$53.9 billion, an increase of 5.1 percent over
the previous year‘s sales of $51.3billion. The
success of the program will have a significant
social and economic impact.
The vice chancellor and president of
UniSA, Prof. David Lloyd, says there are
no international barriers to great research
and development, explaining, “We are
thrilled to have forged such a strong collaboration in China that will enhance the
development of new therapies for cancer, a
disease that continues to present one of our
greatest global challenges. We look forward
to working closely with Yabao Pharmaceuticals with the shared goal of developing
novel anti-cancer agents for patients in
China and globally.” n
EDITCONNECT: E101505
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DISCOVERY
Discovery boom in Southern California
UCSD releases news
on a trio of studies that
have promise for drug
discovery efforts
BY JEFFREY BOULEY
SAN DIEGO—Summer was a busy time at the
University of California, San Diego (UCSD),
and not simply because students were trying to cram in more beach time before the
academic year roared into full force again.
Here is a roundup of three therapeutics
discovery breakthroughs announced by
UCSD over the course of about a month
recently.
Corrected protein structure
reveals drug targets for cancer,
neurodegenerative diseases
A UCSD study in August revises the
previously published structure of the protein
kinase C (PKC) enzyme, which opens up
the possibility of new strategies to turn the
enzyme “on” to treat cancer or “off” to treat
neurodegenerative diseases.
PKC is a family of enzymes that controls
the activity of other proteins in a cell
by attaching chemical tags, which helps
determine cell survival or death. When it
goes awry, UCSD notes, a number of diseases
may result. In a study published August 13 in
Cell Reports, researchers at the UCSD School
of Medicine reveal what they say is a more
accurate structure of PKC, providing new
targets for fine-tuning the enzyme’s activity
as needed to improve human health.
“By understanding how PKC clamps itself
closed, we can now look for ways to wedge it
open to keep it active,” said Dr. Alexandra C.
Newton, a professor of pharmacology. “This
has great potential for developing therapies
for cancer, in which keeping the enzyme
in its ‘on’ position will promote tumor cell
death. We also want to do the opposite in
neurodegenerative diseases, in which we
need treatments that keep neurons alive.”
Researchers typically use a technique
called X-ray crystallography to determine
the 3D structure of proteins, but sometimes
TRIGGER
CONTINUED FROM PAGE 6
muscle—tissues that play important roles
in obesity and type 2 diabetes. The links between obesity and type 2 diabetes have long
been a central focus of Proud’s research.
As he told The Advertiser, a South
Australian news publication, “We had no
idea [the genes] were involved in obesity
and Type-2 diabetes. Normally they are
not doing anything bad ... but testing in
animal models found they were crucial
to weight gain when a high-fat diet was
consumed.”
The researchers at SAHMRI are already
anticipating the potential for their discovery
to lead to new treatments. One challenge
they face is that MNK cannot be removed
from humans, as it was in the mice that
researchers used for their study. The likely
alternative to deleting the gene would be
to use a drug to block its function. Proud’s
researcher team plans to launch further stu-
they have to make assumptions in order to fit
the data together as best they can. In a 2011
study, a different research group resolved
most of PKC’s structure and made their best
guess at how all the pieces fit together, UCSD
explained in a news release.
But that structure didn’t add up with the
biology of how PKC works, and Newton and
her team collaborated with the research team
of another professor of pharmacology, Dr.
Susan Taylor, to take another look at how to
connect the parts, or domains, of the enzyme.
They came up with a different structure and
tested it using a sophisticated cellular imaging technique to visualize whether PKC was
properly packed together or not.
The researchers found that PKC’s calciumsensing (C2) domain interacts with its own
tail and enzymatic domain (the part that
does the chemical tagging, a process known
as phosphorylation), locking the enzyme
in an inactive pose. PKC begins to activate when calcium triggers the bridging of
the C2 domain to the cell membrane, thus
opening the enzyme for activity. The team
also validated this packing by mutating
specific parts of the protein that hold the
domains together, unlocking and relocking
PKC between unpacked and correctly packed
structures.
“Knowing the interfaces that hold PKC closed will now allow the design of small molecules that can either disrupt the interactions
between PKC’s domains to open up and activate the enzyme, or clamp the domains closed to prevent its activation,” said first author
Dr. Corina Antal, who was a graduate student
in Newton’s lab at the time of the study.
Regenerating liver
tissue without forming tumors
Researchers at the UCSD School of Medicine
recently discovered a population of liver cells
that are better at regenerating liver tissue
than ordinary liver cells, or hepatocytes. The
study, published August 13 in Cell, is the first
to identify these so-called “hybrid hepatocytes,” reportedly showing that they are able
to regenerate liver tissue without forming
tumors that lead to cancer. The study was
done on mouse models, but the researchers
dies to explore the therapeutic potential for
such a drug in humans.
Proud has applied for an Australian patent to protect the therapeutic applications
of MNK, and he is considering taking steps
in North America and Europe to pave the
way for development of any drugs that
follow from his research. “We’re working
with local colleagues at University of South
Australia, and others in the United Kingdom, Singapore and perhaps China for drug
development,” he noted.
SAHMRI is a medical research institute
that was launched in 2009 by the South
Australian government in Adelaide, South
Australia. The institute focuses its research on several themes and Proud is “theme
leader” for the the Nutrition and Metabolism division.
In other recent SAHMRI news over the
summer related to obesity, it was noted
that University of Adelaide researchers
have discovered a high-fat diet may impair
important receptors located in the stoma-
also found similar cells in human livers.
The team led by Dr. Michael Karin, Distinguished Professor of Pharmacology and
Pathology, traced the cells responsible for
replenishing hepatocytes following chronic
liver injury induced by exposure to carbon
tetrachloride, a common environmental
toxin. In doing so, they discovered a unique
population of hepatocytes located in a
specific area of the liver called the portal
triad. These special hepatocytes, the researchers found, undergo extensive proliferation and replenish liver mass after chronic
liver injuries. Since the cells are similar to
normal hepatocytes, but express low levels of
bile duct cell-specific genes, the researchers
called them “hybrid hepatocytes.”
“Although hybrid hepatocytes are not stem
cells, thus far they seem to be the most effective in rescuing a diseased liver from complete failure,” said Dr. Joan Font-Burgada,
postdoctoral researcher in Karin’s lab and
first author of the study.
While induced pluripotent stem cells
(iPSCs) have shown promise in the area of
regenerative medicine, they can continue to
proliferate after they’ve done their therapeutic task, which is where cancer risk comes
into play. To test the safety of hybrid hepatocytes, Karin’s team examined three different
mouse models of liver cancer. They found
no signs of hybrid hepatocytes in any of the
tumors, leading the researchers to conclude
that these cells don’t contribute to liver cancer caused by obesity-induced hepatitis or
chemical carcinogens.
Epigenetic driver of glioblastoma
provides new therapeutic target
Cancer’s ability to grow unchecked is often
attributed to cancer stem cells, a small fraction of cancer cells that have the capacity
to grow and multiply indefinitely. How
cancer stem cells retain this property while
the bulk of a tumor’s cells do not remains
largely unknown. Using human tumor
samples and mouse models, researchers at
the UCSD School of Medicine and UCSD’s
Moores Cancer Center discovered that
cancer stem cell properties are determined
by epigenetic changes—the chemical modich that signal fullness. As published in the
journal PLOS ONE, researchers from the
University’s Centre for Nutrition and Gastrointestinal Diseases—based at SAHMRI—investigated the association between
hot chili pepper receptors (TRPV1) in the
stomach and the feeling of fullness, using
laboratory studies.
“The stomach stretches when it is full,
which activates nerves in the stomach to
tell the body that it has had enough food.
We found that this activation is regulated
through hot chili pepper or TRPV1 receptors,” according to Amanda Page, an associate
professor and senior research fellow in the
University of Adelaide’s School of Medicine,
as well as lead author on the paper.
“It is known from previous studies that
capsaicin, found in hot chilies, reduces
food intake in humans. And what we’ve
discovered is that deletion of TRPV1 receptors dampens the response of gastric
nerves to stretch, resulting in a delayed
feeling of fullness and the consumption of
fications cells use to control which genes
are turned on or off.
The study, published in the Proceedings of
the National Academy of Sciences, reported
that an enzyme known as lysine-specific
demethylase 1 (LSD1) turns off genes
required to maintain cancer stem cell properties in the aggressive brain cancer known as
glioblastoma, and this epigenetic activity
helps explain how glioblastoma can resist
treatment. As such, drugs that modify LSD1
levels could provide a new approach to treating glioblastoma.
The researchers first noticed that genetically identical glioblastoma cells isolated
from patients differed in their tumorigenicity, or capacity to form tumors, when
transplanted to mouse models. This observation suggested that epigenetics, rather
than genetics, determines tumorigenicity in
glioblastoma cancer stem cells, according to
UCSD.
“One of the most striking findings in our
study is that there are dynamic and reversible
transitions between tumorigenic and nontumorigenic states in glioblastoma that are
determined by epigenetic regulation,” said
senior author Dr. Clark Chen, an associate
professor of neurosurgery and vice chair of
research and academic development at the
UCSD School of Medicine.
Probing further, Chen’s team discovered
that the epigenetic factor determining
whether or not glioblastoma cells can
proliferate indefinitely as cancer stem cells is
their relative abundance of LSD1. LSD1 removes chemical tags known as methyl groups
from DNA, turning off a number of genes
required for maintaining cancer stem cell
properties, including MYC, SOX2, OLIG2
and POU3F2.
“This plasticity represents a mechanism
by which glioblastoma develops resistance
to therapy,” Chen said. “For instance, glioblastomas can escape the killing effects of
a drug targeting MYC by simply shutting it
off epigenetically and turning it on after the
drug is no longer present. Ultimately, strategies addressing this dynamic interplay will be
needed for effective glioblastoma therapy.” n
more food. Therefore part of the effect of
capsaicin on food intake may be mediated
via the stomach. We also found that TRPV1
receptors can be disrupted in high fat diet
induced obesity.”
Dr. Stephen Kentish, National Health
and Medical Research Council Fellow
at the University of Adelaide’s School of
Medicine noted these findings will inform
further studies and the development of
new therapies, adding “It’s exciting that
we now know more about the TRPV1 receptor pathway and that the consumption
of capsaicin may be able to prevent overeating through an action on nerves in the
stomach. The next stage of research will
involve investigation of the mechanisms
behind TRPV1 receptor activation with
the aim of developing a more palatable
therapy. We will also do further work to
determine why a high-fat diet desensitizes
TRPV1 receptors and investigate if we can
reverse the damage.” n
DISCOVERY
CREDIT: MOPHOSYS
MorphoSys (pictured here) and fellow German company Immatics Biotechnologies recently
formed a strategic alliance related to antibody-based therapeutics against multiple proprietary
cancer antigens recognized by T cells.
TUMAP
novel cancer targets that would be otherwise
inaccessible for antibody-based therapies,”
said Dr. Marlies Sproll, chief scientific officer
of MorphoSys. “This alliance opens up the
intracellular target space for us and thus
complements the therapeutic approaches we
use in other oncology programs. We believe
this collaboration will create several unique
product opportunities for us based on truly
differentiated compounds.”
Tumor cells differ from healthy cells in
the expression of tumor-associated proteins.
These proteins are degraded inside living
cells into shorter fragments, called peptides,
which are then shuttled to the cell surface.
Specialized receptors on the cell surfaces,
so-called major histocompatibility complex
(MHC) receptors, display these peptides to
the external environment, thereby providing
a snapshot of the cell’s interior.
The therapeutic programs now being
pursued by Immatics and MorphoSys aim to
discover Ylanthia antibodies against these
MHC-bound peptide targets in order to
kill the tumor cells. Immatics’ XPRESIDENT discovery platform is, according to
the company, the only known highthroughput research technology to directly identify, quantify and prioritize these
cancer-related peptides.
MorphoSys’ pipeline reportedly is home
to more than 100 human antibody drug
candidates for cancer, rheumatoid arthritis,
Alzheimer’s disease and other disorders.
Immatics focuses on developing cancer
immunotherapeutics. The company’s most
advanced product, IMA901, is a combination of TUMAPs designed to treat kidney cancer and is the subject of a Phase 3
clinical trial that is expected to generate
final results later this year.
“The alliance with MorphoSys marks an
important strategic milestone for Immatics.
We are now entering the field of antibodybased therapeutics complementing our existing cancer immunotherapy pipeline,” according to Dr. Harpreet Singh, chief scientific
officer of Immatics Biotechnologies. “The
combination of MorphoSys’ outstanding
capabilities to create antibodies and the
unique access to intracellular targets through
our XPRESIDENT discovery engine provides both partners the opportunity to jointly
deliver the next generation of transforming
antibody drugs for cancer patients with high
unmet medical need.”
In other recent MorphoSys news, the
company in late September published
updated safety and preliminary efficacy data
on its proprietary drug candidate MOR202
from an ongoing Phase 1/2a study. MOR202
is a fully human HuCAL antibody targeting
CD38, a highly expressed and validated target
in multiple myeloma. The clinical data are
said to confirm the very good overall safety
profile previously reported at this year’s
annual meeting of the American Society of
Clinical Oncology (ASCO). The update also
includes promising first results from the
highest dose escalation cohort of 16 mg/kg
of MOR202 weekly plus dexamethasone, and
from the recently initiated combination arms
with the immunomodulatory drugs (ImiDs)
pomalidomide and lenalidomide.
“The MOR202 data have matured nicely
since we presented the program at this
year’s ASCO conference, and we expect
an even more comprehensive picture as
the trial progresses. First results from the
combination cohorts with lenalidomide
and pomalidomide confirm the synergistic
potential we have demonstrated in preclinical studies using our antibody together with
these two IMiDs. This bodes well for the
future development of MOR202,” said Dr.
Arndt Schottelius, chief development officer
of MorphoSys.
MorphoSys earlier in September also provided an update on the clinical development
outlook for its proprietary drug pipeline, noting that over the last several years, “MorphoSys has built one of the broadest and most
differentiated biopharmaceutical pipelines
in the biotechnology sector.” With the first
partnered programs approaching the market
and the company’s proprietary portfolio gaining momentum, MorphoSys says it intends to
“The alliance with MorphoSys marks an important
strategic milestone for Immatics. We are now entering
the field of antibody-based therapeutics complementing
our existing cancer immunotherapy pipeline.”
Dr. Harpreet Singh, chief scientific officer of
Immatics Biotechnologies
commit additional resources to advance its
programs through approval-enabling studies
and become a commercial organization.
“MorphoSys has successfully transitioned from a technology provider to a drug
development organization. With a robust set
of proprietary drug candidates, now is the
time to scale our investment to ensure that
we capture the full value of our portfolio,”
according to Dr. Simon Moroney, CEO of
MorphoSys AG. “We aspire to become a
fully integrated and commercial biopharmaceutical organization with our own
products on the market. Our lead cancer
compound MOR208, for which we have a
comprehensive development plan, will be
at the forefront of this process.”
MorphoSys’ proprietary activities are currently focused on three clinical candidates:
the hemato-oncology programs MOR208
and MOR202, for which MorphoSys holds
worldwide commercial rights, and the
prostate cancer program MOR209/ES414,
which is being co-developed with Rockville,
Md.-based Emergent BioSolutions. MorphoSys is also planning to commence clinical
relevant cancer targets. Immatics remains
committed to the validity of its discovery
platform and technologies, which we believe
will open up a range of indications for treatment with cancer immunotherapy. It is our
intention to focus our development efforts
from now on our novel Adoptive Cellular
Therapies through our recently announced
major collaboration with MD Anderson Cancer Center.”
For more on that MD Anderson collaboration, see the briefs in the left-hand sidebar
on page 6. n
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“This alliance opens up the intracellular
target space for us and thus complements the
therapeutic approaches we use in other
oncology programs. We believe this
collaboration will create several unique
product opportunities for us based on truly
differentiated compounds,” says Dr. Marlies
Sproll, chief scientific officer of MorphoSys.
studies of MOR106 and MOR107 in 2016
in inflammatory and fibrotic indications,
respectively.
As for Immatics, it also had some lateSeptember news, announcing the results of
a pivotal Phase 3 clinical trial with IMA901
in patients with metastatic renal cell carcinoma (RCC) in combination with sunitinib.
The trial did not meet its primary endpoint
of showing an overall survival benefit of
IMA901 in combination with sunitinib
compared with sunitinib alone in the patient
population.
Dr. Carsten Reinhardt, chief medical officer of Immatics, noted that “It is disappointing that the Phase 3 trial did not generate the
anticipated overall survival benefit. We will
continue to review the data to gain a better
understanding of these results. The observation that the magnitude of immune responses was significantly below expectations based
on the previous results of IMA901, when acting as a single agent, may partly explain that
clinical finding and asks for better means
of mounting active immune cells against
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EDITORIAL
The price of doing drugs...
er, drug development
N
BY JEFFREY BOULEY
ORMALLY, WHEN WE talk about
prices in the pages of DDNews or
in our online venues, it’s about
things like research and development—i.e., the costs of discovering new entities, poking and prodding them for
potential efficacy, getting them through trials
and all the in-betweens of that. Our news coverage only occasionally goes beyond approvals,
and even that is rare. Discovery through trials is
our bread and butter, and once the drug is being
advertised and sold, it’s outside our wheelhouse.
That said, though, two names have come
up in the news to talk about pricing of prescription drugs—Hillary Clinton and Martin
Shkreli—and both of their recent churning of
the waters could have a potential impact on precommercialization efforts. So, I’m going to step
outside our wheelhouse this month.
Like I said, normally I don’t care about how
much a drug costs. (Unless, of course, I’m buying
pharmaceuticals for me and my family, in which
case I care enough sometimes to use very colorful language that might put my very immortal
soul in jeopardy.) As part of her campaign for
the Democratic Party presidential nomination,
though, Clinton proposed government regulation of drug prices; so has Bernie Sanders, but
his comments didn’t stir people up as much,
because such stands are pretty much expected
from him. Here are a couple industry responses:
Researchers and scientists across the
biopharmaceutical industry have dedicated their
lives to the search for new treatments and cures
■■
for patients. They do this against seemingly insurmountable odds, knowing that despite years
of work on potential medicines, nine out of 10
will fail during clinical trials and the process
will start over. This persistence and dedication to patients has resulted in tremendous
advances against some
of life’s biggest enemies,
including cancer, hepatitis C, heart disease and
other terrible diseases.
Secretary Clinton’s proposal would turn back
the clock on medical
innovation and halt
progress against the
diseases that patients Jeffrey Bouley,
DDNews Chief Editor
fear most. These
sweeping and far-reaching proposals would
restrict patients’ access to medicines, result
in fewer new treatments for patients, cost
countless jobs across the country and erode our
nation’s standing as the world leader in biomedical innovation. —Pharmaceutical Research and
Manufacturers of America (PhRMA)
The proposal released today by the Clinton
campaign would do irreparable harm to the
nation’s health innovation system, significantly
hindering the ability of emerging biotechnology
companies to develop the new cures and therapies that patients need to live longer, more
productive lives. Intrusive government regulation of a system that relies on entrepreneurial
vision and private capital is a recipe for failure.
—Biotechnology Industry Organization
■■
Also from PhRMA is a poll that suggests that
the vast majority of voters (86 percent) say
encouraging the development of new medicines should be an important priority for the
next president and congress, with a majority of
voters (53 percent compared to 37 percent) of
the opinion that encouraging the development
of new medicines should be more of a priority
than reducing spending on prescription medicines, despite the latter being the focus of some
candidates’ policy proposals.
And then you have Shkreli, CEO of Turing
Pharmaceuticals, who made headlines globally
in recent weeks for defending his company’s
decision to raise the price of Daraprim—a
medication used to treat toxoplasmosis in
AIDS patients—more than 4,000 percent after
acquiring the rights to the drug. Mind you, this
is a 62-year-old drug his company acquired for
$55 million. Public outrage did force Shkreli
to announce a price reduction, though as of
press time for this issue, that price hadn’t been
announced—it isn’t likely to go back down to
less than $20 per tablet, but who knows how
close it will be to the $750 he was shooting for.
Bottom line: I don’t like the idea of painting pharmas and biotechs as merely greedy
companies, given the kind of costs they incur
and rates of failure they must endure that many
other industries do not. But at the same time
as we try to hold back the politicians from
questionable levels of control, can we please
shame people like Shkreli out of the business
so they don’t perpetuate pharma’s undeserved
predatory characterizations? n
Reader discretion is advised
S
en to be broadly applicable is not to
offend, but to encourage adding back
more clinical pharmacology, or what
listeners) may find this
some call pharmacophenomics.
next feature offensive.
I’ve further suggested that the
Analogous phrases are a
notion of conflicts of interest (incendaily occurrence today
tives for malfeasance) is frequently
as we cower in fear of offending
misplaced and confused with the
those with certain sensitivities. In
multiple good confluences of interthe extreme case, good people have
est (incentives for good) that more
died over mocking cartoons. Graduoften drive research to the benefit of
ation speakers have withdrawn in
Peter T. Kissinger
patients. In my last column, I argued
response to student groups expressing their contrary views. On my own campus that it is equally specious to drive a minimum
there have been grumblings about speakers on wage up or the price of a cancer drug down by
climate change presenting a point of view preju- rule or royal decree. In both cases the consediced by sponsorship from fossil fuel interests. quences are known to be harmful. Sure, there
In these columns I’ve suggested waves in have been egregious examples of profiteering
science that came on too strong. For example, with drug pricing, but that’s not a reason to
molecular biology overwhelming conventional replace condemnation by arbitrary mandate. A
mammalian pharmacology; high-throughput few months ago, I enjoyed the book Pharmacoscreening of enormous libraries overwhelming phobia, How the conflict of interest myth underrational drug design; and genomics creating mines American medical innovation. The author,
a tsunami, with expectations far out of reach. Tom Stossel, is a clinician and professor at
Meeting expectations is hard. Proteomics Harvard Medical School and brother of the TV
hasn’t done that either, falling flat with respect libertarian John Stossel.
My goal in presenting alternatives is to particto biomarkers proven to be diagnostically useful. Laboratories and taxpayers invested a great ipate in debate, but often I’ve been attacked for
deal in these topics, and we made good progress, being a contrarian and even accused of undertypically within narrow contexts. Pointing out mining research funding by creating doubt. The
the fact that pharmacogenomics has not prov- Stossel book supports the societal transition on
BY PETER T. KISSINGER
OME READERS (viewers/
these things from ‘you are innocent ‘til proven
guilty’ to ‘you are guilty until proven innocent’ to
‘don’t bother innovating, the compliance paperwork
overwhelms.’ Transparency in disclosing relationships makes a lot of sense to me, but forbidding
participation in research given a mere appearance of a relationship does not. After all, DTC
advertisements of pharmaceuticals describe
many adverse possibilities to a degree that has
little consequence. It’s somewhat like the fine
print that arrives with a retirement fund prospectus—most of us buy the product and accept
the risk. You’d have to be retired to have time
to read about it.
For the past few years in academia, in parallel with drug ads, some advocate that “trigger
warnings” be issued before a course is taken or
lecture is given that might damage a student
emotionally. The sensitivity of various demographics seems at a fever pitch, similar to the
sensitivity of autocratic governments to a free
press. Some of us remember the “free speech
movement” intended to enable political activity
and antiestablishment speech on college campuses. Forty years later, this began to look like
“the free speech only for those who agree with
us movement.” The writer Jonathan Rausch has
suggested a DTC warning statement for higher
education. “WARNING. At this university, stuDISCRETION CONTINUED ON PAGE 11
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EDITORIAL
COMMENTARY: Defeating lupus starts with a diagnosis
BY PETRA BUDDE AND
PETER SCHULZ-KNAPPE OF PROTAGEN
A
UTOIMMUNE DISEASES ARE
more widespread than many
might appreciate: systemic
lupus erythematosus (SLE)
for example, affects as many
as five million people worldwide 1 , yet
remains without any significant therapeutic options. The underlying cause of SLE is
yet to be deciphered, but it is known that
B cells play a central role in its pathogenesis, which includes antibody-dependent and
antibody-independent mechanisms, such
as the presentation of autoantigens, T cells
and the production of proinflammatory and
regulatory cytokines2. High circulating levels
of autoantibodies that are reactive with DNA/
RNA molecular complexes, and the deposition of such autoantibody-immune complexes,
can induce the activation of dendritic cells,
which can promote the progression of SLE
and organ damage3. Symptoms can vary between patients, yet the vast majority of those
living with SLE have to cope with joint pain
and swelling, leading to arthritis in many
cases. More severe symptoms can affect the
brain and nervous system, kidneys, digestive
tract, vascular system and internal organs.
One of the challenges at the heart of
tackling this disease is the intense difficulty
associated with reaching an accurate diagnosis early in the disease. This is due to the
first symptoms of SLE often overlapping with
other rheumatic diseases or resembling other
disorders and infectious diseases. While R&D
in the pharmaceutical industry has continued
despite this highly diverse disease presentation, approval for novel medicines for SLE
has lagged behind that of other autoimmune
diseases such as rheumatoid arthritis (RA).
In fact, the FDA has approved only one
novel treatment for SLE in the past 50 years
(Benlysta). This isn’t due to any sort of relaxed approach to R&D, but rather a collection
of hurdles in front of the developers:
The pathogenesis of SLE is multifactorial, including genetic, environmental and
hormonal factors.
There are differences among ethnic
groups relating to disease prevalence, disease
activity, clinical manifestations, autoantibody
serology and efficacy of treatments4.
The natural course of disease with periods of relapse and remission strongly affects
clinical outcome regardless of treatment.
SLE patients treated with placebos (in
addition to standard of care) show significant
response rates, and different disease activity
indices (e.g. SLEDAI and BILAG) often
yield different drug and placebo response
■■
■■
■■
■■
DISCRETION
dents could be exposed, at any moment,
without warning, to ideas, comments,
readings or other materials that they find
shocking, offensive, absurd, annoying, racist, sexist, homophobic, discriminatory or
generally obnoxious. We call this education.” Fortunately, the trigger warning
idea engendered the University of Chicago
statement on free speech adopted earlier
this year. A few months later, we proudly
accepted the concept at Purdue.
My New York education in the 1960s
rates5. This makes demonstrating superior
efficacy over a placebo very difficult, and
predicting treatment response essential for
efficient clinical development and regulatory
approval.
The heterogeneity amongst SLE patients
is a major obstacle for pharmaceutical
development and remains something that
the industry needs
to overcome before
work on identifying
effective and curative therapies will
succeed. Clearly,
there is a need for
new technologies
and biomarkers
that allow for the
Petra Budde
definition of more
homogeneous subgroups of SLE patients who
are more likely to respond to a new treatment. Using the full power of biomarkers
for SLE patient stratification and treatment
response prediction should therefore prove
essential for efficient clinical development
and regulatory approval.
The diagnostic gap
Existing diagnostics (Dx) for SLE are somewhat limited, lacking a highly sensitive but
disease-specific test. The detection of antinuclear antibody (ANAs) staining patterns
in patient blood using immunofluorescence
microscopy is the most commonly applied
starting point. The problem with these tests
lies in their relatively low degree of specificity. ANA tests, for example, will produce a
positive result in approximately 98 percent
of SLE patients. While this may seem like
a highly promising test, approximately 20
percent of healthy individuals also receive
the same positive result6,7. Therefore, despite
ANAs having an excellent level of sensitivity
for SLE, the conversely low degree of specificity makes using ANAs in isolation suboptimal due to the risk of overdiagnosis, or even
misdiagnosis8,9.
An alternative to ANA tests are antiextractable nuclear antigen (ENA) antibody tests and anti-double-stranded DNA
(anti-dsDNA) antibody tests which are also
established criteria of the American College
of Rheumatologists’ (ACR) SLE classification. Anti-dsDNA antibodies are found in up
to 70 percent of SLE patients at some point
during the course of the disease—even prior
to the onset of clinical symptoms10. However, anti-dsDNA titres tend to fluctuate in
SLE patients11, and today’s commercial tests
differ in their sensitivity and specificity in
detecting SLE.
provided deep training in accepting and
delivering insults of the worst kind. They
bound my contemporaries together. It’s
best to be civil, but that varies with perceptions. Garbage can be more productively
ignored than forbidden. Those students
who avoid exposure of this kind may have
limited resilience later. The genome is not
going to help sort this out. We also now
know that pharmacogenomics will have
utility, but very limited. Admit it and get
back to work. The recent passing of Yogi
Berra reminds me of the inflexibility of colleagues in contrary life-science cocoons.
“It was impossible to get a conversation
The anti-cyclic citrullinated peptide
(CCP) antibody, an established marker in
the diagnosis and prognostication of RA, can
also be useful in SLE patients. SLE patients
occasionally develop an erosive arthritis
similar to that of RA. Recent research has
shown that the anti-CCP antibody can be
employed as a highly specific marker of
erosive arthritis in SLE12.
Throwing the diagnostic
kitchen sink at SLE
To help overcome the deficits in existing methods, an array approach is preferable. This makes it possible to combine the
strengths of individual tests while mitigating
some of their known weaknesses. Together,
it becomes possible to build up an accurate
composite picture of
the type of SLE and
even disease severity
in a patient. Lupus
nephritis, for example, is associated
with particular levels of anti-C1q and
anti-dsDNA antibodies that tend to
Peter Schulz-Knappe
precede flare-ups of
disease activity. Anti-U1-RNP autoantibodies
are associated with Raynaud’s phenomenon
and a reduced probability of nephritis. Autoantibody profiles like these make it possible
to diagnose or even predict SLE-associated
organ damage.
Disease activity and severity can be
similarly determined by assessing distinct
autoantibody profiles that are characteristic of different aspects of the disease (e.g.
combined anti-Ro/La antibodies are associated with secondary Sjögren’s syndrome
(SjS) and photosensitivity, but a lower risk
of nephritis).
A suite of autoantibody assays that extend
traditional Dx, such as anti-dsDNA tests,
offers clinicians the ability to define subgroups of SLE patients. The recently developed SLE stratification array (NavigAID SLE,
from Protagen) distinguishes between four
main groups of SLE patients. Groups range
from a highly reactive patient group who
have a high disease activity score and possess broad and homogenous positive autoantibody reactivity, through to a smaller
group of patients who have comparatively
low levels of autoantibody reactivity. These
distinct groups were defined via the analysis of over 1,000 SLE patient samples with
different disease states and ethnicities. This
has generated a distinct collection of SLEspecific autoantibody profiles that provide
going, everybody was talking too much.”
When the biology proves more complicated, the Yogi escape is brought to the fore:
“I never said most of the things I said.”
For one final trigger warning, the opinions
expressed here do not imply endorsement
by DDNews, Purdue University or the commissioner of major league baseball. n
Peter T. Kissinger (who can be reached at
[email protected]) is professor of
chemistry at Purdue University, chairman
emeritus of BASi and a director of Chembio
Diagnostics, Phlebotics and Prosolia.
the framework for future diagnostic research
into not only SLE, but autoimmune diseases
in a much broader sense.
Early steps toward
better Dx and better treatment
With these diagnostic foundations in place,
there is now the capacity to begin implementing array techniques that enable accurate diagnoses of SLE patients and the prediction of an individual’s disease state and severity. The subgroups of SLE patients generated
from autoantibody profiles raise the possibility of defining different SLE immunotypes,
and thus the rationale for assigning patients
to certain therapies. Such a therapeutic
response prediction can be beneficial to the
subsequent development of companion diagnostics (CDx). It is hoped that pharmaceutical companies will eventually begin to align
CDx development with clinical programs for
SLE treatment, allowing those trials to benefit from the highly relevant patient stratification. Implementation of CDx combats the
“one-size-fits-all” approach to drugs used in
the treatment of autoimmune diseases, and
form part of a market that has already been
identified as having significant potential for
revenue generation. In addition to patient
health and possible financial benefits, a drugCDx co-development model during clinical
trials could result in the earlier identification
of possible side effects, a shortening of overall
trial lengths, improved success rates to reach
the patient and numerous improvements to
drug efficacy and safety.
For now, diagnostic arrays facilitate highly
useful definitions of homogenous groups of
SLE patients. Such Dx allow for accurate
diagnoses, patient stratification, response
prediction and potentially form the basis of
autoimmune CDx. n
Petra Budde is head of medical research at
Protagen, with responsibility for both leading
the SLE biomarker development program
and commercial projects. She has 15 years of
experience in proteomics biomarker research
in the field of diabetes and autoimmune
diseases.
Peter Schulz-Knappe joined Protagen in 2010
as chief scientific officer. He has a strong
scientific background, having trained as
a medical doctor before working as a cell
biologist, and brings over 25 years of protein
and peptide biochemistry experience, coupled
with biomarker discovery and development
expertise. He has more than 15 years of
management experience in R&D.
For the full version
of the above commentary,
which has the footnotes
and references,
go to our website at
www.ddn-news.com and
search for the Editconnect
number above: E101535
The opinions expressed in guest
commentaries do not necessarily
represent those of DDNews and/or its
owners, editors or other staff.
BRIEFS
SYGNIS, GeneWorks ink
distribution deal
HEIDELBERG, Germany— SYGNIS AG and Gene-
Works Pty Ltd. have signed a non-exclusive distribution agreement for the commercialization of
SYGNIS’ proprietary product portfolio in Australia.
Per the terms of the agreement, GeneWorks will
be granted the rights to promote, market and sell
all existing and future products, including SYNGIS’ TruePrime products for primer-free WGA and
SunScript thermostable reverse transcriptase kits
for the translation of RNA into DNA to scientists
working in genomics, proteomics and diagnostics
in Australia. No financial details were disclosed.
“We are very pleased about the distribution
agreement with GeneWorks for the Australian
continent, which significantly strengthens our
worldwide presence and perfectly positions our
products in the rapidly growing biotechnology
industry,” Pilar de la Huerta, CEO and chief financial officer of SYGNIS, said in a press release.
BD finalizes Cellular
Research purchase
FRANKLIN LAKES, N.J.—BD Life Sciences, a segment
of leading global medical technology company BD
(Becton, Dickinson and Company), recently completed its acquisition of Cellular Research Inc., which
brings with it advanced tools for massively parallel
single-cell genetic analysis based on its proprietary
Molecular Indexing technology. The companies
have been collaborating since September 2014 to
develop single-cell analysis workflows for Cellular Research’s Precise product line and BD’s FACS
instruments and software, and presented a study
at the Advances in Genome Biology and Technology
Meeting demonstrating that the combined workflow can enhance the detection and quantification
of expression in single and/or multiple cell samples.
Linda Tharby, executive vice president and
president of BD Life Sciences, said that “The addition of Cellular Research builds on our GenCell
acquisition and underscores BD’s commitment to
a genomics strategy focused on next-generation
sequencing sample preparation.”
INVOKING FITZGERALD
Scripps Florida
scientists’ structural
discoveries could aid in
better drug design
BY LLOYD DUNLAP
JUPITER, Fla.—Some concepts—the general
theory of relativity and aspects of quantum
mechanics come to mind—are sufficiently
complex that attempts to explain and understand them are elusive. So when The Scripps
Research Institute (TSRI) references F. Scott
Fitzgerald, who once said that the test of a
first-rate intelligence is the ability to hold
two opposed ideas in mind at the same time
and still retain the ability to function, you
can expect to be challenged. “Now, scientists from the Florida campus of The Scripps
Research Institute (TSRI) have found the biological equivalent of that idea, or something
very close,” TSRI said in its release announcing the results of their work.
The abstract of the article titled “Structural mechanism for signal transduction in RXR
nuclear receptor heterodimers,” published
Researchers at TSRI’s Florida campus have uncovered the structural details of how some
proteins interact to turn two different signals into a single integrated output. Pictured here is
TSRI’s main campus in La Jolla, Calif.
recently in Nature Communications, explains:
“A subset of nuclear receptors (NRs) function as obligate heterodimers with retinoid
X receptor (RXR), allowing integration of
ligand-dependent signals across the dimer
interface via an unknown structural mecha-
nism. Using nuclear magnetic resonance
(NMR) spectroscopy, X-ray crystallography
and hydrogen/deuterium exchange (HDX)
mass spectrometry, here we show an allosteric mechanism through which RXR cooperTSRI CONTINUED ON PAGE 13
Jackson Lab launches
precision genetics center
Center’s mission is to create
disease models to develop therapies
for life-threatening and genetically
complex conditions
CREDIT: THE JACKSON LABORATORY
BY ZACK ANCHORS
BAR HARBOR, Maine—The flood of human genetic data that has
IN THIS SECTION
Dealmaking
BD finalizes Cellular
Research purchase.................................. 12
SYGNIS, GeneWorks ink
distribution deal...................................... 12
Drug design
Invoking Fitzgerald................................... 12
Genomics/Sequencing
Jackson Lab launches
precision genetics center........................ 12
Two advances in sequencing prep.......... 16
Inflammation
Inflammation intervention....................... 14
emerged in recent years presents researchers with a significant
challenge: using this abundant genetic information to create more
sophisticated disease models that can be used in preclinical research.
A new Center for Precision Medicine at The Jackson Laboratory (JAX)
will be focused on doing just that.
JAX, a non-profit biomedical research institute, announced last
month that it had received a nearly $10-million grant from the
National Institutes of Health (NIH) to fund its new center. The
center’s mission is to create precision models of disease that can be
used to develop therapies for life-threatening and genetically complex
human diseases.
“This center allows us to build on work that we’ve been doing
for many years and to leverage our ongoing programs and expertise
in mammalian genetics,” Rob Burgess, principal investigator of the
center, tells DDNews. “There has been an ongoing interest here in
this kind of disease modeling, and this grant allows us to formalize
The Jackson Laboratory is funding its new Center for Precision
Medicine thanks in large part to a nearly $10-million grant from the
National Institutes of Health.
that pipeline and to discover how we can best model diseases in the
mouse genome.”
The center will be based in JAX’s Bar Harbor, Maine, headquarters
but will serve as a hub for an international, multidisciplinary team
that includes geneticists and genetics technology experts, molecular
and computational biologists, clinical experts in specific disease
areas and world leaders in the development of precision mouse modJAX CONTINUED ON PAGE 16
TSRI
ates with a permissive dimer partner, peroxisome proliferator-activated receptor (PPAR)-γ, while
rendered generally unresponsive
by a non-permissive dimer partner,
thyroid hormone (TR) receptor.
Amino acid residues that mediate
this allosteric mechanism comprise an evolutionarily conserved
network discovered by statistical
coupling analysis (SCA). This SCA
network acts as a signaling rheostat
to integrate signals between dimer
partners, ligands and coregulatorbinding sites, thereby affecting
signal transmission in RXR heterodimers. These findings define
rules guiding how NRs integrate
two ligand-dependent signaling
pathways into RXR heterodimerspecific responses.”
For the first time, the TSRI team
has uncovered the structural details
of how some proteins interact to
turn two different signals into a
single integrated output. These
new findings could aid future drug
design by giving scientists an edge
in fine-tuning the signal between
these partnered proteins—and the
drug’s course of action.
“Thyroid, vitamin D and retinoid receptors all rely on integrated signals—their own signal
plus a partner receptor,” said TSRI
Associate Prof. Kendall Nettles,
who led the study with TSRI colleague Associate Prof. Douglas Kojetin. “These new findings will have
important
implications for
drug design
by clearly defining
exactly how
these signals
b e c o m e
i n t e g ra t e d ,
Kendall Nettles
so we will
be able to predict how changes
in a drug’s design could affect
signaling.”
Using a number of complementary technologies, including nuclear magnetic resonance, X-ray
crystallography and hydrogen/
deuterium exchange mass spectrometry from the laboratory of
Scripps Florida colleague Chair of
the Department of Molecular Therapeutics Patrick R. Griffin, the
scientists were able to determine
the mechanism through which
two signaling pathways become
integrated.
The study focused on a small
subset of nuclear receptors, a large
family of proteins that regulate
gene expression in response to
signals from various binding partners, including steroids and fats.
Once receptors sense the presence
of these binding partners, they send
out new signals that initiate other
cellular processes.
“ Nuc lea r receptors bind
different types of molecules, and
some of these receptors physically
interact with each other to integrate different signals,” Kojetin said.
“Earlier studies basically accepted
this without any structural evidence for communication between
receptors. This is the first time that
anyone has looked at what’s actually
going on at the atomic level.”
In addition to Nettles, Kojetin
and Griffin, authors of the study
include Edna Matta-Camacho, Travis S. Hughes, Sathish Srinivasan,
Jerome C. Nwachukwu, Valerie
Cavett, Jason Nowak, Michael J.
Chalmers, David P. Marciano and
Theodore M.
Kamenecka of
TSRI; Andrew
I. Shulman of
the University
of California,
Irvine; Mark
Rance of the
University of
Cincinnati;
Douglas Kojetin
and John
B. Bruning of The University of
Adelaide.
The work was supported by the
National Institutes of Health, the
Frenchman’s Creek Women for
Cancer Research, the James and
Esther King Biomedical Research
Program, the Florida Department
of Health and the State of Florida.
TSRI is one of the world’s largest independent, not-for-profit
organizations focusing on research
in the biomedical sciences. TSRI
is internationally recognized for
its contributions to science and
health, including its role in laying
the foundation for new treatments
for cancer, rheumatoid arthritis,
hemophilia and other diseases. An
institution that evolved from the
Scripps Metabolic Clinic founded
by philanthropist Ellen Browning
Scripps in 1924, the institute now
employs about 2,700 people on its
campuses in La Jolla, Calif., and
Jupiter, Fla., where its renowned
scientists—including two Nobel
laureates—work toward their next
discoveries. The institute’s graduate program, which awards Ph.D.
degrees in biology and chemistry,
ranks among the top 10 of its kind
in the nation. n
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Inflammation
intervention
Botanisol wins NIH grant for anti-inflammatory compound
that could bypass side effects of NSAIDs
BY KELSEY KAUSTINEN
SCOTTSDALE, Ariz.—The global anti-
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© 2015 Thermo Fisher Scientifi c Inc. All rights reserved. All trademarks are
the property of Thermo Fisher Scientifi c and its subsidiaries unless otherwise
specifi ed. CO018139 0915
inflammatory drug market currently
exceeds $60 billion, with non-steroidal
anti-inflammatory drugs (NSAIDs)
standing as one of the most common
treatments for moderate to acute inflammatory pain. In fact, NSAIDs account
for some $12 billion in sales globally each
year, but their usefulness comes with a
cost—NSAID usage has been linked to
bleeding ulcers, kidney problems, stroke
and heart attacks in a number of studies
and reports, with recent data highlighting greatly increased risk for cardiovascular complications for individuals
over the age of 65. As a result, NSAID
usage leads to 100,000 hospitalizations,
17,000 deaths and roughly $2 billion in
healthcare costs each year in the United
States alone.
Despite those side effects, NSAIDs
remain a standard of care for their
effectiveness, but Arizona-based Botanisol recently received a grant for the
development of a potential new option—
TAI-LCx—for treating inflammation
“What we know about TAILCx is very encouraging.
Through the grant, we will
learn a great deal more about
its structure and effect on
other inflammatory pathways.
The expertise, support and
facilities at WSU, especially
the TIPL lab, are ideal for us.”
Dr. David Gang, chief science
officer of Botanisol
without the health risks of NSAIDs.
The company was informed on August
9 that it would receive a competitive
grant award from the National Institutes
of Health (NIH) and National Center for
Complementary and Integrative Medicine (NCCIM). According to Botanisol
CEO P. Scott Waterhouse, the grant is
worth just under $225,000 and is the
full amount they requested. Government funding issues being what they
are, he says they were “a bit surprised
by that, but obviously overjoyed.” The
funding will support three parts of TAILCx’s development.
The cause for NSAIDs’ dangerous side
effects is their very method of action.
As noted by the American College of
Rheumatology on the organization’s website, NSAIDs work by blocking enzymes
that produce prostaglandins, “a group of
naturally occurring fatty acids that play
a role in pain and inflammation. Older
NSAIDs like ibuprofen block two of these
enzymes, COX-1 and COX-2.”
Waterhouse explains that “It’s the
mediation of the COX2 enzyme, cyclooxygenase 2 enzyme, that causes the cardiovascular side effects of the NSAIDs,”
while COX1 “is the enzyme that protects
the stomach lining and kidneys, and as a
An experimental compound, TAI-LCx, may hold promise for treating inflammation
without the health risks associated with NSAIDs like aspirin, ibuprofen, naproxen,
celecoxib and acetaminophen.
result, the NSAIDs that mediate COX1
are the ones that have the gastrointestinal side effects and cause the kidney
problems and the adverse effects of
NSAIDs.”
Botanisol’s new compound, however,
could offer a way to avoid the issue of
COX inhibition. The compound in question is called TAI-LCx, short for turmeric
anti-inflammatory lipophilic compound.
TAI-LCx, says Waterhouse, is an extraction from the turmeric root, but from
the essential oils of the root, not from
the more popular curcamin. The compound was originally discovered at the
University of Arizona via a multiyear
NIH-supported research program, and
Botanisol is the exclusive licensee of the
patented technologies.
The most promising feature of TAILCx is its method of action; rather than
impacting COX1 or COX2, Waterhouse
says the compound directly affects TNFα
(tumor necrosis factor alpha), PEG2 and
one or two of the interleukins. In rat models of rheumatoid arthritis, he says TAILCx “was shown to be as effective or more
effective than indomethacin, but with a
much better safety profile than indomethacin, so there’s a lot of early information that is really quite positive with
the initial compound TAI-LCx.” With this
recent NIH/NCCIM grant, Botanisol will
be able to further explore the nature and
method of action of TAI-LCx.
“The original discovery was based
upon three different methods of extraction at laboratory-scale. Each of these
three have some shortcomings, not to
mention that they’re difficult ones to
scale up for manufacturing,” Waterhouse
tells DDNews. “So the first piece of our
next stage that we now have funded is
a commercially scalable extraction process to separate the very specific compound in very high quality and very high
purity. Part two is additional studies of
the structure of the compound. We’re
looking for the exact chemical structure and molecular weight, etc., of the
compound, along with researching the
existing compound to look for variants
that will have different and more specific
anti-inflammatory activity, either on the
inflammatory processes in the body or
even specific tissues.
“Then the third piece of this is additional studies of the biologic activity
so that we can expand our knowledge.
The original research only researched,
I think, five or six of the inflammatory
pathways, and we’re going to expand that
to a whole suite of inflammatory pathways and hopefully have a very thorough
map of exactly how the compound is
working.”
Dr. David Gang, chief science officer
of Botanisol, will direct the new research
at rented laboratories at Washington
State University. Gang commented in a
press release that, “What we know about
TAI-LCx is very encouraging. Through
the grant, we will learn a great deal more
about its structure and effect on other
inflammatory pathways. The expertise,
support and facilities at WSU, especially
the TIPL lab, are ideal for us.”
Botanisol is a translational biopharmaceuticals company focused on applying modern science to known bioactive
constituents of plants with the goal of
getting safer, more affordable drugs
and healthcare products into the pipelines of pharmaceutical and healthcare
companies.
“What we have found is there’s really
a very large inventory of plant sources in
research that have determined the biologic activity of different constituents
of plants, but these have never been
researched using modern science and
new techniques to discover, find and
develop their drug properties ... There
are reports that even the existing modern Western medicines have as much
as 25 percent plant material in them to
begin with. We’re just kind of stepping
back in time and saying it’s now time
to find out what Mother Nature knew
about medicines and use that knowledge to develop better medicines that
are probably safer and more affordable,”
Waterhouse remarks. n
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of Cellular Dynamics International, Inc. CO124790 0715
Two advances in sequencing prep
Roche and Lumora make
a deal and Fluidigm
enhances its C1 system
BY JEFFREY BOULEY
PLEASANTON & SOUTH SAN FRANCISCO,
Calif.—This summer saw Roche sign a defini-
tive asset purchase agreement with Lumora
for products associated with the Heat Elution technology for nucleic acid purification
of multiple sample types. The technology is
intended to work not just with
straightforward samples but also
with challenging formalin-fixed
paraffin-embedded (FFPE) tumor
samples.
The purpose for the deal:
Roche wants to explore integration of this technology into its
sequencing workflow solution, noting that
“Today, nucleic acid purification technology
from specimens including formalin-fixed
tissues can be cumbersome and inefficient.
Lumora’s highly differentiated proprietary
methodology will enable simple and automated nucleic acid isolation in minutes
instead of hours.”
be integrated to an automated sequencing
workflow, which makes it an ideal fit for
Roche’s sequencing vision of a sample-in/
results-out workflow,” said Dan Zabrowski,
head of Roche Tissue Diagnostics and the
Roche Sequencing Unit in Pleasanton, Calif.
“An important bottleneck in sequencing
workflow is nucleic acid extraction. Heat
Elution technology significantly simplifies extraction and is simple to automate.
The acquisition of this technology may
offer Roche a unique position in
fully integrated sequencing devices,” said Laurence Tisi, CEO of
Lumora.
Meanwhile, around the same
time as the Roche-Lumora deal
was being inked, in another part
of California (South San Francisco, to be precise), Fluidigm Corp. announced
commercial availability of a new highthroughput single-cell mRNA sequencing
workflow for its C1 system to enable largescale studies to characterize heterogeneous
samples.
The company notes that this validated
workflow includes “a new advanced inte-
“An important bottleneck in sequencing
workflow is nucleic acid extraction. Heat Elution
technology significantly simplifies extraction
and is simple to automate. The acquisition of
this technology may offer Roche a unique
position in fully integrated sequencing devices.”
Laurence Tisi, CEO of Lumora
In addition, the technology is reportedly
environmentally friendly and can be applied
to process a wide variety of sample types that
include whole blood, fecal matter, sputum,
FFPE tissue and buccal swabs. The Heat Elution technology is currently for research use
only, not for use in diagnostic procedures.
“Lumora’s Heat Elution technology can
JAX
CREDIT: THE JACKSON LABORATORY
els of disease. JAX expects that
the center will collaborate with
researchers from Emory University, Cedars Sinai Medical Center,
the San Diego and San Francisco
campuses of the University of
California, Columbia University
Medical Center, Nationwide Children’s Hospital and the University
of Massachusetts Medical School.
Scientists at JAX’s new genomic
medicine institute in Farmington, Conn., are also expected to
contribute to research.
The grant offers funding over
five years, with just a little over
$1.99 million available during
the first year. The initial funding
will be used to launch six projects
and to engage several of Jackson
Lab’s core scientific services, such
as a bioinformatics pipeline, that
could improve the precision of
grated fluidic circuit (IFC) and reagent kit
that significantly increases throughput and
ease of use, while simultaneously decreasing
the cost of preparation and sequencing (by
maximizing sequencer capacity) on a percell basis. The C1 mRNA Seq HT application
is the first and only commercial product to
address large single-cell studies and is avail-
CREDIT: ROCHE
TOOLS &
TECHNOLOGY
Roche recently made a deal with Lumora to purchase products associated with the unique,
patent-protected Heat Elution technology for nucleic acid purification of multiple sample types,
including FFPE tumor samples. Pictured here is Roche Sequencing in Pleasanton, Calif.
able today.”
Researchers reportedly can apply the new
HT workflow to explore heterogeneity in
fields such as cancer, neuroscience, stem cell
biology and immunology to understand how
the underlying cellular mechanisms impact
biological processes or disease progression.
This new offering is a complete solution that
enables scientists to deeply explore the diversity of cell subpopulations, quickly discover
novel or rare cell types and increase the statistical sample size to better estimate biological
variation between similar cell types.
The C1 mRNA Seq HT IFC is said to capture up to 800 cells at a time, and employs
a new protocol to facilitate two runs—1,600
cells total—a day. Additionally, the IFC features two-cell loading inlets to facilitate caseversus-controls studies, allowing users more
flexibility in their experimental design. The
assay protocol enables on-IFC multiplexing
and cell pooling that provides users with a
streamlined workflow. According to Fluidigm, the complete workflow reduces custom-
“This center allows us to build on work that
we’ve been doing for many years and to leverage
our ongoing programs and expertise in
mammalian genetics,” says Rob Burgess, principal
investigator of The Jackson Laboratory’s new
Center for Precision Medicine. “There has been an
ongoing interest here in this kind of disease
modeling, and this grant allows us to formalize
that pipeline and to discover how we can best
model diseases in the mouse genome.”
disease models and the efficiency
of the preclinical pipelines being
developed at the center.
Burgess tells DDNews that each
of the center’s six initial projects
will be focused on a different disorder. The project led by Burgess
will examine Charcot-MarieTooth disease, an incurable neurological disorder. “We have a
specific disease variant that we’ve
been studying in mice for the last
ten years,” says Burgess. “My project is working to humanize those
models.”
The other five projects are
focused on epilepsy, neuromuscular disease, macular degeneration
and kidney disease. “What really
makes this center interesting and
unique is the breadth of disorders
we are researching, rather than
just focusing on cancer or a single
disease area,” says Burgess.
JAX President and CEO Edison
Liu said in a statement that JAX
was awarded the grant largely due
to its long-established expertise
in mammalian genetics and disease modeling, paired with the
human clinical samples, data
and collaborations of the new JAX
er library preparation costs by approximately
85 percent when compared to the original
C1 mRNA Seq IFC costs, while maintaining
the automation and reproducibility of the C1
platform, and Fluidigm maintains that it is
the only single-cell workflow that also allows
automated staining to visualize the isolation
and viability of individual cells.
“Our knowledge of cell populations is
largely limited by our ability to precisely
study many cells at a transcriptome level,”
said Gajus Worthington, Fluidigm’s president
and CEO. “The C1 mRNA Seq HT application
substantially alleviates this challenge—our
customers can now process 1,600 cells per
day for transcriptome sequencing. Unlike
error-prone, expensive and laborious manual methods such as FACS with plate-based
workflows, the C1 mRNA Seq HT workflow
provides a high-throughput, easy-to-implement, reliable and low-cost solution not
previously available to single-cell researchers exploring cell heterogeneity.” n
Genomic Medicine operation in
Farmington.
“Ultimately,” Liu said, “the
center will generate new disease
modeling processes and pipelines,
data resources, research results
and models that will be swiftly shared through JAX’s proven dissemination pipelines to
accelerate translation to medical
benefit.”
Burgess tells DDNews that the
NIH has also awarded grants to
fund the creation of two other
centers for precision genetics,
both of which will be focused on
creating disease models for various forms of cancer. One center
will be at the Tisch Cancer Institute at Mount Sinai Hospital
and another at Memorial Sloan
Kettering Cancer Center. “It will
be valuable to have the opportunity for us to interact with other
centers and learn what they are
doing and to find out what’s
working and what isn’t so we can
optimize disease modeling,” says
Burgess. n
“Ultimately, the center will generate new
disease modeling processes and pipelines,
data resources, research results and
models that will be swiftly shared through
JAX’s proven dissemination pipelines to
accelerate translation to medical benefit.”
Edison Liu, CEO of The Jackson Laboratory
Let’s talk.
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PRECLINICAL
BR IEFS
Dismantling
viruses
Oncodrone awarded grant for
OCD155 development
AMSTERDAM—Anticancer company Oncodrone
recently announced that it had received a
€2.5-million (approximately $2.8 million) grant
from Eurostars, a joint program between EUREKA
and the European Commission. The grant will
support the development of OCD155, Oncodrone’s lead drug for the treatment of prostate
cancer, enabling the company to progress the
drug through preclinical development toward
clinical trials and further explore its mechanism
of action, which will be done in a Dutch-DanishGerman-Swiss consortium, including the partners
Radboud UMC and Leiden UMC. OCD155 blocks
epithelial to mesenchymal transition in cancers,
thereby halting tumor progression and, in the lab,
has been shown to reduce tumor burden, reduce
tumors’ ability to spread and treat advanced
stages of disease.
Bruker unveils new preclinical
imaging systems
HONOLULU—The World Molecular Imaging Congress 2015 saw Bruker introduce four new preclinical imaging systems designed to deliver improved
performance and convenience, as well as offer
new options for advanced translational research.
The new offerings include the next-generation
Albira Si PET/SPECT/CT System, the new BioSpec
3T preclinical MRI System with cryogen-free hagnet, a next-generation PET/MRI System (BioSpec
3T PET/MRI) and the new, high-sensitivity Xtreme
II Optical Molecular Imaging System. Dr. Wulf
Jung, president of Bruker’s Preclinical Imaging
Division, said: “[We] are pleased to respond to
our customers’ demand for a translational research
3 Tesla preclinical MRI with robust cryogen-free
magnet technology. Our optical molecular imaging
capabilities have also been further enhanced to
meet customer expectations.”
IN THIS SECTION
Alzheimer’s disease
A model mouse....................................... 21
Herpes
Dismantling viruses ................................ 18
Imaging
Bruker unveils new
preclinical imaging systems ................... 18
News roundup
Setting the stage for development ........ 20
Oncology
NCI grant pushes
forward bone cancer research ............... 18
Oncodrone awarded
grant for OCD155 development.............. 18
Regenerative medicine
Hope or hype for spinal injuries? ........... 19
NanoViricides
reports two successful
studies of topical
antiherpes treatment
in animal models
BY ILENE SCHNEIDER
SHELTON, Conn.— NanoViricides Inc.,
of diagnosis. Typically the disease is treated
with surgery and chemotherapy.
The rarity of the disease is a major reason why little research has gone forward in
recent decades focused on developing more
effective treatments. “There has been very
little motivation for industry to focus on this
disease,” Gorlick acknowledges.
However, Gorlick says that several lines
of research hold promise for osteosarcoma
patients. Clinical trials are currently underway to test such things as immuno-therapies,
monoclonal antibodies, bone cell treatments
and new chemotherapy agents. CHAM and
the Montefiore Einstein Center for Cancer
Care are currently engaged in three of these
clinical trials and plan to begin more trials
soon. One of the trials is testing a drug that
has already been approved by the U.S. Food
and Drug Administration for treating breast
cancer and that researchers believe could
have efficacy towards osteosarcoma.
The new NCI funding will support preclinical studies of five to 10 novel investigational
treatments each year. The most promising
drugs will be selected to be used in clinical trials that involve children and teens. “What we
will do is screen drugs through human tumors
as means of trying to determine whether
a development-stage nanomedicine
company developing antiviral drugs,
has reported successful results in two
studies, showing dramatic improvements in clinical symptoms associated
with herpes simplex virus infection in
an animal model. The company believes
that a drug that is superior to existing
therapies could result in significantly
expanded market size; the current market size for herpes simplex virus treatments is already larger than $2 billion
annually.
Dr. Anil Diwan, co-founder of NanoViricides, sought to create a medicine
that neutralizes the virus in the patient’s
body and can be administered after the
patient has contracted a disease. If the
theory he developed in 1992 and has
been working on since then is successful, there will be effective treatments for
a variety of viruses. As he explained in
an article by Scott Alexander in NYSE
Intercontinental Exchange, “I started
thinking about the interaction between
viruses and cells and how we might be
able to impact a virus’ life cycle.”
NanoViricides is creating specialpurpose nanoviricide drug candidates
designed to specifically attack enveloped virus particles and to dismantle
them; nanoviricide is the company’s
name for its biomimetic antiviral
medicines. The company is developing
drugs against a number of viral diseases
including H1N1 swine flu, H5N1 bird
flu, seasonal influenza, human immunodeficiency virus, oral and genital
herpes, viral diseases of the eye like
epidemic keratoconjunctivitis and herpes keratitis, hepatitis C, rabies, dengue
fever and Ebola.
The antiviral therapeutics called
nanoviricides are designed to look to the
virus like the native host cell surface to
which it binds. Because the binding sites
for a given virus do not change despite
mutations and other changes in the
CHAM CONTINUED ON PAGE 21
HERPES CONTINUED ON PAGE 20
The National Cancer Institute (pictured here) recently awarded a grant of $1.3 million to the
Children’s Hospital at Montefiore and the Albert Einstein Cancer Center to find more effective
treatments for a rare form of bone cancer.
NCI grant pushes
forward bone
cancer research
Though most common bone cancer in children,
osteosarcoma’s rarity limits study funding
BY ZACK ANCHORS
NEW YORK—Survival rates for many types
of cancer have improved dramatically in
recent decades, but the prognosis for osteosarcoma is about the same today as it was in
the 1970s. A new $1.3-million grant awarded
to the Children’s Hospital at Montefiore
(CHAM) and the Albert Einstein Cancer
Center (AECC) is aimed at finally making
some progress toward more effective treatments for the rare disease, which is a form
of bone cancer. The institutions announced
last month that they had received the
National Cancer Institute (NCI) grant to
support preclinical studies aimed at developing new therapies.
“We clearly need new drugs with efficacy
to improve survival,” Richard Gorlick, vice
chairman of the department of pediatrics at
CHAM, tells DDNews. “This research, which
would not be possible without this grant,
will help us make progress towards that
goal.” Gorlick, who has made osteosarcoma
a major focus of his career, will be leading
the research program funded by the grant.
Only about 800 cases of osteosarcoma are
diagnosed in the United States each year,
although it is the most common form of
bone cancer in children. It is most commonly
found in teens, with 15 being the average age
PRECLINICAL
Hope or hype for spinal injuries?
Asterias announces
preclinical data
supporting the safety
and use of AST-OPC1
as a treatment for
spinal cord injury
BY LLOYD DUNLAP
MENLO PARK, Calif.— Asterias
Biotherapeutics Inc., a
biotechnology company specializing in the emerging field of
regenerative medicine, has
announced the publication of
a manuscript in Regenerative
Medicine relating to AST-OPC1
(oligodendrocyte progenitor
cells). The publication describes
the results from preclinical safety
studies that were submitted to the
U.S. Food and Drug Administration
as part of an Investigational New
Drug application. AST-OPC1 is currently in a Phase 1/2a dose-escalation clinical trial for complete cervical spinal cord injury (SCI).
The preclinical results showed
that AST-OPC1 cells did not cause
any adverse clinical observations,
toxicities, allodynia or tumors.
AST-OPC1 exhibited robust persistence and limited migration
within the thoracic and cervical spinal cord. In addition,
AST-OPC1 demonstrated nerve
growth-stimulating properties
and remyelinating properties that
supported restoration of function
in animal models.
“The positive preclinical results
support the general safety of AST-
OPC1 and indicate minimal risk
of the transplanted cells reaching
unintended locations,” said Dr.
Edward Wirth, chief medical
officer. “In addition, the results
indicate that AST-OPC1, when
administered during the subacute
phase of SCI, can act through
multiple repair pathways that are
relevant to SCI, including trophic
factor signaling, cavity reduction
and stimulation of axon outgrowth
and myelination. We believe that
the results summarized in this
manuscript support the continued
clinical development of AST-OPC1
as a subacute treatment for SCI.”
The publication, titled “Preclinical Safety of hESC-Derived
Oligodendrocyte Progenitors Supporting Clinical Trials in Spinal Cord
Injury,” appeared online ahead of
the print edition of Regenerative
Medicine. The majority of safety
testing was conducted in nude
rats subjected to thoracic SCI, providing a well-established model of
the target clinical population, and
additional tumorigenicity studies
were conducted in uninjured SCID/
bg mice. Importantly, these rodent
models enabled testing of ASTOPC1 in a large number of subjects
and in an immunocompromised
environment that was permissive to
human cell survival. Both of these
attributes facilitated assessment of
key safety concerns associated with
AST-OPC1 administration, including
the resultant biodistribution, toxicity
and tumorigenic potential of the transplanted cells.
“The breadth and depth of the
Smart assays KNOW INDIGO!
Asterias Biotherapeutics’ AST-OPC1, currently in a Phase 1/2a doseescalation clinical trial for complete cervical spinal cord injury, reportedly
caused no adverse clinical observations, toxicities, allodynia or tumors, and
it exhibited robust persistence and limited migration within the thoracic
and cervical spinal cord.
preclinical studies now published
provided the basis for a successful first-in-man Phase 1 study with
AST-OPC1, and set up the foundation for overall safety in support
of the use of AST-OPC1 in other
neurological diseases, including
multiple sclerosis and stroke,” said
Jane Lebkowski, president of resea-
rch and development and chief scientific officer at Asterias.
Not everyone agrees, though.
In a somewhat scathing analysis,
Seeking Alpha goes to some length
to develop and underscore its criticism. Asterias is repackaging old
clinical data as new, the analysts
claim, writing in part that “it is
worth pointing out that Asterias
has not presented any new data
or shown further development
of Geron’s stem cell portfolio.
[Geron was the original owner of
the intellectual property]. The recent investor meeting that Asterias
held on May 8, 2015, was more or
less a review of Geron’s previously
presented data on AST-OPC1.
Asterias did review the trial design
of their current Phase 1/2a clinical trial of AST-OPC1, which is
underway. However, this clinical
trial is nearly identical to Geron’s
initial Phase 1 conducted in 2010,
which Geron terminated midway
through because the compound
failed to show any signs of efficacy.”
Asterias is a biotechnology
company that specializes in the
emerging field of regenerative
medicine. The company’s proprietary platforms are based on its
pluripotent stem cell and dendritic
cell immunotherapy technologies.
Asterias is focused on developing
therapies to treat conditions in
several medical areas with high
unmet medical need and inadequate available therapies. AST-OPC1 is
currently in a Phase 1/2a dose escalation clinical trial in spinal cord
injury. AST-VAC1 (antigen-presenting autologous dendritic cells) has
demonstrated promise in a Phase 2
study in acute myelogenous leukemia. AST-VAC2 (antigen-presenting allogeneic dendritic cells)
represents a second-generation,
allogeneic approach to dendritic
cell vaccines. n
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PRECLINICAL
Setting the stage for development
Rounding up some recent news of preclinical studies and results around the world
CREDIT: TSRI
Zealand presents new data on ZP-I-98
COPENHAGEN, Denmark—Zealand Pharma
A/S presented new preclinical data on its
novel GIP receptor agonist, ZP-I-98, at the
51st European Association for the Study of
Diabetes annual meeting that took place
Sept. 14-18 in Stockholm, Sweden. One
investigational approach to enhance the
efficacy of GLP-1 receptor agonists, used for
the management of type 2 diabetes, includes
combination therapy with a glucose-dependent insulinotropic peptide (GIP) receptor
agonist. Recent preclinical studies conducted
in diet-induced obese mice by Zealand with
its novel GIP receptor agonist, ZP-1-98, have
shown that a GIP/GLP-1 combination therapy
could enhance the treatment of type 2 diabetes by inducing both robust glycemic control as well as a greater loss of body weight
than seen by a single treatment. ZP-1-98 has
a long-acting profile, which indicates that it
could be suitable for convenient once-weekly
dosing.
HERPES
virus, the company believes that its drugs
will be broad-spectrum and thus effective
against most, if not all, strains, types or subtypes of a given virus.
The nanoviricide technology enables
direct attacks at multiple points on a virus
particle to render it ineffective at infecting cells. Antibodies, on the other hand,
attack a virus particle at only a maximum
of two attachment points per antibody. The
nanoviricide simultaneously allows for
attacking the rapid intracellular reproduction of the virus by incorporating one or
more active pharmaceutical ingredients
“We have made
substantial progress
in this financial year,
with our new stateof-the-art, c-GMP
manufacturing
capable campus, and
further progress
in our HerpeCide
program, which is
now at advanced
preclinical stage.”
Dr. Eugene Seymour,
CEO of NanoViricides
Authors of a new study on “erasing” drug use
memories included (left to right) Scripps
Florida’s Sherri Briggs, Ashley Blouin,
Courtney Miller and Erica Young.
on selectively erasing these dangerous and
tenacious drug-associated memories.
“We now have a viable target and by blocking that target, we can disrupt, and potentially erase, drug memories, leaving other
memories intact,” said Courtney Miller, a
TSRI associate professor. “The hope is that,
within the core of the nanoviricide.
In April, the company reported on studies performed in the laboratory of Dr. Ken
S. Rosenthal, a leading researcher in herpes virus antiviral agents and vaccines, at
Northeast Ohio Medical University, where
Dr. Rosenthal is a professor emeritus. Two
of the antiherpes nanoviricides reduced
the morbidity and mortality of the HSV1-infected animals that were treated. These
nanoviricides also reduced virus production in cell culture. Topical dermal treatment with these nanoviricides led to almost
complete survival (more than 85 percent)
of the infected mice in this animal model.
All untreated animals died of the disease.
Further, these nanoviricides were superior
to topical treatment with an acyclovir formulation that was employed as a positive
control.
Recently, NanoViricides reported on
studies performed by TransPharm Preclinical Solutions, a preclinical services
company in Jackson, Miss. All of the
nanoviricides tested improved clinical
scores dramatically, with clinical presentation being arrested at redness or simply raised local lesions, and a complete
absence of zosteriform spreading. All of
the animals treated with nanoviricides
survived the lethal HSV-1 infection challenge for the duration of the study, while
untreated animals died toward the end
of the study.
The nanoviricides are designed as topical
treatment for the breakout of herpes sores.
Some of the nanoviricides found effective
in the previous study were tested in this
study for the confirmation of efficacy in a
dermal animal model in Balb-c mice using
the same highly aggressive and neurotropic
when combined with traditional rehabilitation and abstinence therapies, we can reduce
or eliminate relapse for meth users after a
single treatment by taking away the power
of an individual’s triggers.”
To accomplish this, the researchers used
a compound called blebbistatin that successfully disrupted long-term storage of drugrelated memories—and blocked relapse for
at least a month in animal models of methamphetamine addiction.
Aerie and Ramot
enter research collaboration
IRVINE, Calif. & TEL AVIV—In mid-September, Aerie Pharmaceuticals Inc., a clinicalstage pharma focused on the discovery,
development and commercialization of
first-in-class therapies for the treatment of
patients with glaucoma and other diseases
of the eye, and Ramot at Tel Aviv University
Ltd., Tel Aviv University’s technology transfer
company, announced a research collaboration and license agreement for a preclinical
anti-beta amyloid small-molecule product
candidate for neuroprotection and dry agerelated macular degeneration.
The proprietary technology was originally
developed by a team headed by Prof. Ehud
Gazit of the George S. Wise Faculty of Life
Sciences at Tel Aviv University. The technology is based on the combination of noncoded
α-aminoisobutyric acid and aromatic recognition module to construct a novel chemical
entity that is a safe and potent inhibitor of
the formation of toxic amyloid assemblies.
CREDIT: TREVENTIS
A
Single injection prevents meth relapse
JUPITER, Fla.—Recovering addicts often
grapple with the ghosts of their addiction—
memories that tempt them to relapse even
after rehabilitation and months, or even
years, of drug-free living. Now, scientists from
the Florida campus of The Scripps Research
Institute (TSRI) have made a discovery that
brings them closer to a new therapy based
QUARTET OF brief stories to
give you a quick peek across
the globe (a few select portions,
anyway) into what researchers
have turned up in preclinical
efforts in recent months.
TRV 101 significantly reduces both
amyloid beta and tau toxic aggregates
PHILADELPHIA—Treventis Corp. announced
this summer that its preclinical candidate
TRV 101 had successfully demonstrated significant reduction in the toxic aggregates/
oligomers of
both amyloid
beta and tau
protein in multiple transgenic
mouse models
of Alzheimer’s
disease. Using
industry-stanComputer simulation of a
dard mouse
drug binding to a mismodels of amyfolded amyloid protein.
loid beta (APP/
PS1) and tau (rTg4510), a reduction of
approximately 30 to 40 percent in both tau
and amyloid beta oligomers was observed in
the brain following oral administration of
TRV 101 over a three- to seven-day period. n
NanoViricides is looking to expand the $2-billion herpes simplex market—and gain a good
chunk of it—with its antiviral technology, which showed mettle against the herpes virus in
recent studies using mouse models.
HSV-1 strain H129c, which was used
previously.
“We have made substantial progress in
this financial year with our new state-ofthe-art, c-GMP manufacturing-capable
campus, and further progress in our HerpeCide program, which is now at advanced
preclinical stage, and additional strong
safety data on injectable FluCide, which is
in IND-enabling studies,” said Dr. Eugene
Seymour, CEO of NanoViricides since
2005. “The topical HerpeCide program
is developing in parallel with our injectable FluCide. The HerpeCide program is
likely to move faster towards clinical trials,
because of the inherent advantages in the
nature of topical drug development.” n
PRECLINICAL
A model mouse
Probiodrug licenses transgenic Alzheimer’s mouse
model to QPS Austria Neuropharmacology
BY JEFFREY BOULEY
HALLE, Germany—Probiodrug AG, a
biopharmaceutical company developing novel therapeutic solutions to treat
Alzheimer’s disease (AD), announced in
early September an agreement to license
its TBA2.1 tg Mouse to QPS Austria Neuropharmacology, a contract research
organization (CRO) focused on central
nervous system drug development that
is based in Grambach, Austria.
The transgenic mouse model has
been developed, characterized and patented by Probiodrug, primarily as part
of efforts to establish a new therapeutic
concept of reducing brain pyroglutamate-modified Abeta (pGlu-Abeta) in
the treatment of Alzheimer’s disease.
Licensing this model to QPS Austria
Neuropharmacology makes it accessible
to a wider community of academic and
industry research groups, Probiodrug
noted in announcing the deal.
“Characterization and use of this
model has been extremely useful for
our understanding of the involvement of
pGlu-Abeta in the initiation and progression of AD,” according to Hans-Ulrich
Demuth, co-founder and former chief
scientific officer of Probiodrug. “This
model is only one of a set of new ADlike models developed by Probiodrug to
establish a comprehensive validation of
pGlu-Abeta as a potential target to treat
Alzheimer’s disease and to extensively
profile potential drug candidates. I’m
very pleased about the collaboration of
Probiodrug with QPS to thereby offer our
TBA2.1 mouse model to the wider AD
and neurodegeneration research.”
Probiodrug has thus far progressed
two complementary strategies for tackling pGlu-Abeta with two medicine
candidates in development: PQ912, a
small-molecule inhibitor of glutaminyl
cyclase, now in Phase 2 clinical trials,
and PBD‑C06, a pGlu-Abeta-specific
mAB that is still in the preclinical stage.
The TBA2.1 transgenic mouse model
overexpresses pGlu-Abeta in neurons
and is suitable to model neuronal loss
and neurodegeneration, characteristics
typical for disease progression, Probio-
CHAM
[they’re] effective or not,” says Gorlick.
“This research should yield new
hope for hundreds of children and
families across the country faced
with a diagnosis of osteosarcoma,” he
notes. “For those of us who have spent
decades researching this challenging
cancer, being able to more systematically screen for new drugs that will
directly impact the course of the
disease is very exciting.”
This grant to AECC and CHAM,
which are both located in the Bronx
䐀䤀匀䌀伀嘀䔀刀夀
Mice are a frequently used animal model in preclinical studies, of course, and recently,
German company Probiodrug licensed its TBA2.1 tg Mouse to QPS Austria
Neuropharmacology for use in Alzheimer’s disease research.
drug noted in the announcement, adding, “These mice represent the most
rapid murine model of Abeta induced
cognitive impairment, demonstrating
the highly toxic nature of pGlu-Abeta.”
Birgit Hutter-Paier, director neuropharmacology at QPS Austria, noted of
the deal that “We are optimistic about
this model being perfectly complementary to QPS’ current range of animal
models for AD drug research. Transgenic
animals are still among the most crucial
tools to investigate drug candidates for
the treatment of AD. The TBA2.1 mouse
model will be a valuable addition to our
portfolio of mouse models addressing
the increasingly multifaceted APP [amyloid precursor protein] pathology, which
still has a prominent and highly relevant
position in the field.”
Though Probiodrug is now focused
on the development of new therapeutic
products for the treatment of Alzheimer’s disease, the company—founded in
1997—is well known for successfully
developing a novel therapeutic concept
for diabetes: DP4 inhibitors, which
provided the basis for a novel class of
antidiabetics known as gliptins. The
company’s core capabilities are based
on its longstanding expertise in the elucidation of the structure and function
of enzymes involved in the modification
of proteins and peptides, which play a
central role in pathological conditions.
QPS Austria is a full-service CRO that
performs preclinical as well as clinical research. The Neuropharmacology
department that licensed Probiodrug’s
mouse model focuses on drug development for neurodegenerative diseases. n
“For those of us who have spent decades
researching this challenging cancer, being
able to more systematically screen for
new drugs that will directly impact the
course of the disease is very exciting.”
Richard Gorlick, vice chairman of the department
of pediatrics at Children’s Hospital at Montefiore
borough of New York City, is part of a
comprehensive NCI preclinical pediatric
research program called the Pediatric
Preclinical Testing Consortium (PPTC).
The purpose of PPTC is to identify
and prioritize new, more effective
treatments for solid tumor and blood
cancers which primarily affect children
and teens. AECC was among the first
academic cancer research centers to be
funded by the NCI. n
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㄀ⴀ㠀㘀㘀ⴀ㌀吀䤀匀匀唀䔀
SPECIAL REPORT
DIAGNOSTICS
Non-invasion of the body snatchers
To avoid tissue biopsy,
researchers are turning to
diagnostic biofluids
I
BY RANDALL C WILLIS
N THE BUSY HALLWAY OF AN urban hospital’s diagnostics
No Cell Left Behind concept: By combining morphological features with immunofluorescence,
CTCs stand out like a sore thumb with Epic Sciences’ cellular analysis platform.
Pass the tissues
Despite the rapid advances in identifying and
understanding the nature of driver mutations
and resistance markers in various cancers—
information that is going a long way to
individualizing patient care—the challenge
of fully characterizing a cancer within a
single patient remains significant. Even in
situations where a solid tumor exists, it is
not always possible to obtain a tissue biopsy
due to clinical inaccessibility or unacceptable
risks to patient safety.
Likewise, with a growing acknowledgement of the cellular diversity inherent within tumors, a single biopsy sample may not
reflect the disease’s heterogeneity, whether
we are considering just the tumor or including its microenvironment.
Cancer is not a static disease, however,
and in its connection to the blood stream and
other bodily fluids, it leaves a biological trail.
The trail comprises circulating tumor cells
(CTCs) that slough from the cancerous mass,
as well as cell-free DNA and RNA (cfDNA
found in patient blood offers oncologists insights on potential prognosis and the
likelihood of progression, as well as helping
to monitor the return of disease.
In August 2013, Janssen Diagnostics
announced the findings of a study conducted
in China of the utility of CellSearch CTC
enumeration in metastatic breast cancer
patients. They determined that patients
with fewer than five CTCs per 7.5 mL of
whole peripheral blood at first follow-up had
significantly longer median progression-free
survival and overall survival versus patients
with CTC counts of five or more.
Despite these outcome trends, the test
tells clinicians little about the disease itself,
such as the mutational baseline or changes
in the prevalence of resistance markers. To
determine these factors—important to clinical decision makers—CTCs have to be isolated for further analysis.
According to Epic Sciences CEO Murali
Prahalad, CTC isolation methods have traditionally fallen into one of two camps.
and cfRNA) that are released as cancer cells
turn over or through other processes.
It is to these biological packets that several companies and research groups have
turned their attention, looking for ways to
characterize cancers more fully and less
invasively in tests known as liquid biopsies.
Cell mates
Just over 145 years ago, Thomas Ashworth
noticed free-floating cells in the peripheral
blood of cancer patients that looked similar
in shape, size and morphology to cells within
the tumors, which eventually led to speculation that this was the route by which tumors
metastasized to other tissues.
It has only been much more recently, however, that technology has allowed researchers to isolate and quantify these CTCs, and
it was only in 2004 that FDA clearance was
achieved for the first CTC-based assay system: CellSearch from Veridex.
With CellSearch, however, the analysis
is purely quantitative. The number of CTCs
CREDIT: EPIC SCIENCES.
wing, Dr. Miles J. Bennell scrambles into a moving crowd
of staff and patients. Bennell is frantic, his eyes wide with
excitement, struggling to catch his breath.
Excitedly, he grabs one person in the hall.
“They’re here, already,” he bellows, only to be shaken off.
Spinning on his heels, he bumps into someone else.
“You’re next,” he yells, repeating the call as he bounces
from person to person.
Warnings of an invasion of alien pods threatening to
replace us all?
No, just a melodramatic diagnostician, excited about the opportunities
for less-invasive biopsies for his cancer patients.
“One said that all cancer cells must have
certain epithelial proteins on their surface
and you could use that to isolate them by
immunomagnetic beads,” he suggests. This
is essentially the way CellSearch functions,
as well as Fluxion’s IsoFlux System.
The second perspective, he continues, suggested that all cancer cells are larger than the
surrounding white blood cells, and so “you
could formulate microfluidic approaches
either to enrich for the CTC or to deplete
the white blood cells.”
This is effectively the idea behind platforms such as Angle plc’s Parsortix and ApoCell’s ApoStream, which also incorporates
a dielectrophoretic component to the
microfluidics.
But as Prahalad explains, cancer has proven to be an incredibly heterogeneous condition, involving cells of all morphological and
molecular profiles. Thus, methods that select
for one characteristic likely come with the
cost of missing some facets of the disease.
DIAGNOSTICS CONTINUED ON PAGE 24
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SPECIAL REPORT
DIAGNOSTICS
With this in mind, Epic researchers developed the No Cell Left Behind concept, where
they first lyse the red blood cells in a sample
and pellet the remaining cells. They then
transfer the cell pellet to a series of slides for
further analysis or storage in a biorepository.
“Each slide has about three million nucleated cells on it,” Prahalad says. “And we’ve
designed a high-speed scanning system that
can look at all three million of those cells
across all fluorescent channels in less than
15 minutes.”
They then rely on imaging software to
identify the cells, whether they be white
blood cells or cancer cells, and assign each
cell on the slide an X-Y coordinate. Prahalad
uses the analogy of Google Earth.
The cells are scanned for a variety of
parameters, most tissue morphology-based.
And when you overlay immunofluorescent
signals, he suggests, “The cancer cells stick
out like a sore thumb.”
Not only does this method allow the
company to see CTCs that they never knew
existed before, Prahalad continues, but
the presence of white blood cells provides
insights into the patient’s immune status.
“As we enter this new world of immunooncology, we can not only interrogate the
cancer cells that are present, we can see
markers like PD-L1 on white blood cells, as
well,” he enthuses. “So we can get an interesting view about not just the cancer, but also
how the immune system may be reacting to
the different cancers.
“I think it’s an ironic twist that the very
cell that everyone thought didn’t matter, the
cell that you wanted to get rid of, we actually
preserve and now we’re in a position to start
to analyze in a very different way.”
A key advantage of looking at whole, individual cells is that it allows researchers to not
only appreciate the cellular heterogeneity of
a patient but to actually use that information
in a clinically meaningful way.
“We see cancer not as a disease of averages
but a disease of multiple clonal species that
exist in a patient, each of which has a unique
genomic and proteomic profile,” he offers,
but adds that this is only the first step.
“It’s not only the presence or absence of
the mutation you’re targeting, but the pres-
“In near real-time—earlier than with
a biopsy, earlier than imaging—you
can observe emerging resistance.
You can plan for a different
therapeutic agent,” notes Antonius
Schuh, CEO of Trovagene, of his
company’s technology to identify
ctDNA signals in urine.
CROWDED FIELD
Improved enrichment and analytical platforms mean
an increasingly busy liquid biopsy market.
Circulating Tumor Cells (CTCs)
SRI Biosciences
Vortex
Creatv
Biosciences
MicroTech
ScreenCell
Angle plc
Apocell
Epic Sciences
ACD
Abnova
IVDiagnostics
CellSearch
Fluxion
Beckman
Coulter
Biocept
Guardant
Health
Thermo Fisher
Trovagene
Sysmex-Inostics
NeoGeneStar
Chronix
Biomedical
Transgenomic
NeoGenomics
System
Biosciences Inc
Exosome
Diagnostics
QIAGEN
Genomic
Health
Cell-Free DNA
(cfDNA)
ence or absence of other resisting clones
that may actually make the patient refractory to what you’re doing,” he presses. “In a
clinical trial context, I have to have a grasp
of the cellular diversity; otherwise, I don’t
really have a sense of what’s happening in
my patient.”
With some collaborations, he continues,
they were able to see changes in the number
and composition of the cells as quickly as one
week after initial administration of a drug.
And you can then chart the evolution and
changes in the cell population over time,
especially in response to therapeutic selec-
Exosomes
tive pressure.
While acknowledging the slow transition
in the CTC field from mere enumeration to
analysis, Trovagene CEO Antonius Schuh is
less convinced of their utility beyond being
biologically interesting.
“These CTCs are cells that, for whatever
biological reason, have decided to leave the
tumor, so they are behaviorally not representative of those cells that you’re concerned
about,” he says, feeling that the speculation
on their role in metastasis is oversimplified.
“If you now give a patient a drug, are you
expecting that the number of CTCs should go
up or down? There is really no basis for that.”
“And the second significant challenge
for CTCs is that they simply will not give
you information about quantitative tumor
dynamics,” he presses.
For these reasons, he and many others
have turned their attention from cells to
cfDNA and ctDNA.
Back in circulation
First noted in the late 1940s, cfDNA arises
when cells of any stripe die, whether through
apoptotic or necrotic processes, and slough
their contents into the surrounding biofluids.
In many cases, this is blood, but in the case
of brain cells, it might also be cerebrospinal
fluid.
And because tumor cells replicate rapidly
as the tumor matures, more and more cells
die with each passing generation, releasing
greater quantities of ctDNA into circulation.
When compared to CTCs, says Guardant
Health CEO Helmy Eltoukhy, cfDNA has
a distinct advantage from a sheer numbers
perspective.
He points to a 2013 study published in the
New England Journal of Medicine that quantified how many copies of specific mutations
occurred in blood samples taken from 30
breast cancer patients. When the blood samples were divided into cellular and cell-free
fractions and analyzed with digital PCR and
sequencing, the researchers found that the
mutational signal was more than 100 times
stronger in the ctDNA than in the CTCs.
“It’s a much richer source of that information, and that richer signal allows you to do
things like capture the heterogeneity that’s
there in the individual or potentially get to
earlier stages of cancer, Stage II and Stage I,”
Eltoukhy says.
As a sign of how quickly this research is
translating into the clinical setting, QIAGEN
announced in January receipt of European
registration for its therascreen EGFR RGQ
Plasma PCR kit for use as a companion diagnostic with AstraZeneca’s Iressa in the treatment of non-small cell lung cancer (NSCLC).
Similarly, in June, both Personal Genome
Diagnostics and NeoGenomics announced
the launch of cfDNA-based liquid biopsy
services. In the case of PGD, the LungSelect
platform identifies somatic sequence mutations and translocations in NSCLC patients
that can be treated with drugs that are FDAapproved or in clinical trial. The NeoLAB
assays from NeoGenomics, meanwhile, cover
12 different mutational profiles in different
hematological disease.
Also working in NSCLC and in the same
month, Guardant Health announced a partnership with the National Cancer Institute
to apply its Guardant360 cfDNA testing
platform for genomic profiling of 600 lung
cancer patients participating in SWOG-1403.
The goal is to test patients upon enrollment
and upon disease progression, and then use
that information to adjust patient therapy.
But even with this early excitement and
richer signal compared to CTCs, there are
still significant technical challenges for
ctDNA-based liquid biopsy, says Trovagene’s
Schuh. His top two are signal dilution and
analyte size.
“ctDNA in the patient is highly diluted,
and you may not be able to observe a signal simply because it’s not present in your
limited sample,” he opens, suggesting that
while the blood of a late-stage cancer patient
might be flooded with ctDNA, patients with
earlier-stage cancers or who have received
SPECIAL REPORT
treatment may simply not present
a lot of signal.
“If I have a Stage III colon cancer
patient with a robust KRAS signal
and then I perform surgery on
that patient, there’s a 50-percent
chance that this patient will transition from Stage III to Stage 0,” he
explains. “If I now want to confirm
that there is no KRAS signal left in
that person, then I will not even
remotely achieve the necessary
sensitivity from a blood sample,
because there is just nothing in
there anymore.”
Thus, rather than looking exclusively at blood samples, Trovagene
has decided to focus much of its
resources on isolating and identifying ctDNA signals in urine, which
clinicians can collect in much larger volumes and more frequently.
But regardless of their starting point, the second challenge
remains that ctDNA and cfDNA is
highly fragmented—on the order
of 150 base pairs—which presents
a problem when you’re trying to
identify mutations using nextgeneration sequencing (NGS),
according to Schuh.
“The system noise for next-gen
sequencers is relatively high, the
floor is about 1 percent,” he says.
“But we need to be able to look at
0.001 percent because the signals
are so diluted. So we need to enrich
those signals by a factor of 100 to
1,000 so that we can reliably see it
with NGS.”
“The way that we do this at Trovagene is we make extremely small
primers, primers that are so short
that by themselves they do not
uniquely map to the genome,” he
continues. “These primers have a
synthetic tail, and they anneal in
the immediate proximity of the
mutation you are interested in.”
By aggressively optimizing
the enrichment assay, Trovagene
increases the likelihood of a
mutation-bearing fragment being
amplified and therefore detected
by NGS.
“Within days to weeks with very
high reliability, we can determine
whether a patient is benefiting
from treatment by observing on
the one side, the initially highly
accelerated cell death, which is
measured by spikes of mutational
signal, and the subsequent depletion of that cellular reservoir,
which is measured by a sustained
vastly reduced mutational signal,”
Schuh enthuses, quoting examples
in NSCLC, pancreatic cancer and
histocytic disease.
“In near real-time—earlier than
with a biopsy, earlier than imaging—you can observe emerging
resistance,” he says. “You can plan
for a different therapeutic agent.”
“Then, rather than waiting many
weeks or months before you know
whether your treatment choice was
a good idea or not, you can accelerate that feedback dramatically,” he
continues. “That’s why we call this
Precision Cancer Monitoring.”
“As we enter this new world of immuno-oncology, we
can not only interrogate the cancer cells that are
present, we can see markers like PD-L1 on white
blood cells, as well. So we can get an interesting view
about not just the cancer, but also how the immune
system may be reacting to the different cancers.”
Murali Prahalad, CEO of Epic Sciences
Pressing the point further,
Schuh sees ctDNA as a reflection
of disease dynamics, a sign that
something is actually happening.
“When we look at oncogene
mutations in tissue, we are look-
ing at something in a static manner,” he explains. “If I obtain this
tissue from a late-stage cancer
patient, it’s reasonably okay to
assume that an oncogene mutation observed in the cancer tissue
is involved in disease progression
and development.”
“But I can also observe a BRAF
mutation in a mole, but that mole
will probably never turn into skin
cancer,” he postulates. “Or I can
even be born with a BRAF mutation—there are people who have
that as germline mutations—and
my risk to develop cancer that is
DIAGNOSTICS CONTINUED ON PAGE 26
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DIAGNOSTICS
associated with that mutation is actually only
moderate.”
“In contrast, if you observe that mutation
in ctDNA, you have one very critical additional piece of information,” he continues.
“You are observing this mutation and it is
originating from cells that are undergoing accelerated turnover. Otherwise, you
wouldn’t even see it.
“The mere fact that I see a KRAS mutation
in a person’s ctDNA tells me not only that it is
there, it also tells me that it is doing something, because the cells that released that signal
into circulation grow and die at an accelerated rate.”
Although Prahalad is quick to note that
companies like Trovagene have done a lot to
amp up analytical specificity and sensitivity,
he raises a cautionary flag about the averaging out of a mutational signal.
Once a cell dies and releases its contents
into the body’s circulation, you may pick up
individual mutations, but you can’t reconstruct the cell of origin, he warns, and that
is vital to understanding what is happening
in these patients.
“There is a big difference biologically if
you have one mutation in five cells or five
mutations in one cell,” he explains. “They
will radically change the biology and likely
change the response to specific therapies.”
Dying cells aren’t the only source of circulating DNA, however, as live cells release
small spheres of biomolecules into circulation, encapsulated in a lipid bilayer known
as microvesicles. One form of microvesicle
is the exosome.
WINDOWS INTO THE BODY
Adapted from Brock et al.
Transl Cancer Res. 2015;4:280-290.
Analysis
CTCs
cfDNA
Exosomes
Mutations (e.g., point mutations, CNVs, InDels, translocations)
√
√
√
Epigenetic changes (e.g., methylation patterns)
√
√
√
Transcriptomics (e.g., mRNA, microRNA, splice variants)
√
X
√
Cell phenotype (e.g., morphology, protein localization)
√
X
X
Inflammatory response (e.g., gene expression changes)
X
X
√
Can use biobanked materials (e.g., frozen plasma, urine, etc.)
X
√
√
CTCs = circulating tumor cells; cfDNA = cell-free DNA; CNVs = copy number variations; InDels = insertion-deletions
Message in a bottle
Thought to be part of a natural signalling
mechanism between living cells, exosomes
are small bubbles of cellular cytoplasm wrapped in protective lipid coats. Once thought to
be essentially garbage bags for cells, there is
growing evidence that these small particles—
often less than 100 nm in diameter—are a
way for cells to securely transfer biomolecules
such as DNA, RNA and proteins across large
distances within the body.
Like CTCs, exosomes provide a window
on active physiological processes within the
body, but tend to occur in vastly larger quantities than the circulating cells. Thus, there is
speculation that these structures may more
accurately reflect what is happening with a
cancerous tumor than ctDNA or CTCs.
A much more recent discovery than the
other two analytes, early efforts to isolate
exosomes focused on ultracentrifugation
methods, but this technique requires
specialized equipment and sample preparation. More recently, however, the aptly
named Exosome Diagnostics has developed
a spin-column approach that greatly accelerates exosome harvesting from plasma.
In September, as part of its partnership
with QIAGEN, the company published a
study in PLoS One that demonstrated its
platform could yield high-quality exosomal
RNA (exoRNA) of equal or higher quantity in a faster timeframe than traditional
ultracentrifugation methods, and with more
consistent results. The study is part of the
collaborator’s efforts to commercialize, via
Two sources of biomolecules:
Whether through rapid cell
turnover (top left) or exosome
release (bottom right), cancerrelated DNA, RNA and proteins
are released into circulation.
CREDIT: EXOSOME DIAGNOSTICS
QIAGEN, a series of research kits under the
exoRNeasy and exoEasy banners to serve
the biomarker discovery and liquid biopsy
markets.
While one part of Exosome Diagnostics pursues the spin-column technology,
however, another part is firmly pursuing
the development of clinical assays to identify
cancer-driving and resistance-building mutations in patient samples. And to do so, the
company isn’t playing favorites with the
analytes it chooses.
“When you’re talking about non-invasive
genotyping—and this is one big application
within the liquid biopsy space—you clearly
wouldn’t want to exclude or ignore one big
source of molecular signal,” says Vince O’Neill,
chief medical officer for diagnostics. “If you
combine captured cfDNA and exoRNA, you
essentially get two to four times the yield than
you would just by looking at cfDNA.”
“Why is that important?” he continues. “In
the non-invasive genotyping space, you want
to maximize sensitivity, and if you look at the
mutation signal from both of these sources,
you can up that sensitivity. It’s as simple as
that, really.”
Thus, the company has a series of tests
that characterize exoRNA plus cfDNA or
exoRNA alone in blood or urine to look for
mutations associated with prostate, lung and
solid tumor cancers.
“There are two big applications here for
our technology,” O’Neill presses. “Molecular
response, where you follow the genetic markers post therapy. What you want to see is a
collapse in the molecular signal. And then,
obviously, molecular relapse, which as the
data suggests will precede clinical or radiographic relapse by weeks to months.”
This lead time is critical to optimizing
patient treatment, according to Exosome
collaborator Keith Flaherty, director of the
Henri and Belinda Termeer Center for Targeted Therapies at the Massachusetts General
Hospital Cancer Center.
“In patients with an aggressive cancer, such
as melanoma, insights about treatment response and disease progression are immensely
time-critical in order to help guide and
adjust treatment strategy,” he said in an
announcement of melanoma data presented
at the annual meeting of the American Society of Clinical Oncology in June.
As part of a longitudinal study that
monitored BRAF-mutant melanoma, the
company and its collaborators noted they
could detect early disease progression
several months before any clinical signs of
progression appeared.
“We’re very encouraged by these data as
they validate the utility of the combined
capture of exoRNA and cfDNA to detect
BRAF,” continued Flaherty. “Moreover, they
demonstrate the ability of this plasma-based
approach to detect disease progression much
sooner than clinical or radiographic evidence, which would represent a potentially
landmark advance in the diagnostic paradigm
for melanoma and a host of other cancers.”
On the back end
Simply isolating the analyte is only the first
step, however, and just as much development
has gone into finding ways to identify rarer
and rarer events, as well as to expanding for
what signals within the analytes researchers
can look.
“Ultimately, the choice of platforms and
required detection limit will depend on the
clinical sample being analyzed, as the most
sensitive methods are reported to detect
allelic frequencies of as little as 0.01 percent, providing a theoretical lower limit to
detect one mutated copy in a background
of 10,000 wild-type alleles,” wrote Graham
Brock and colleagues at Exosome Diagnostics in a recent review in Translational Cancer Research. “Thus, this level of sensitivity requires samples/patients where at least
10,000 target alleles enter the downstream
analytical assay.”
As one of the key steps in identifying the
needle in the haystack is enlarging the needle, PCR-based methods of signal amplification have seen significant improvements over
the last few years.
In June, for example, Transgenomic
announced its plans to launch up to six new
cancer tests within the year based on its Multiplexed ICE COLD-PCR (MX-ICP) platform.
Originally licensing the platform from the
Dana-Farber Cancer Institute, the company
suggests the system can amplify mutant signal
more than 500-fold over background signal,
offering detection rates down to 0.01 percent.
In August, the company announced the
launch of a pilot project to validate MX-ICP
to guide and monitor live clinical trials being
run by several unnamed pharma companies.
“As we have already shown in our own studies, we expect to validate for our partners
that MX-ICP liquid biopsies are comparable
or superior to DNA analyses obtained from
conventional FFPE tissue samples,” said Transgenomic President and CEO Paul Kinnon
in announcing the project. “We believe liquid
biopsies will ultimately improve a clinician’s
ability to diagnose and treat cancer, and they
should also help to improve patient stratification in clinical trials and accelerate FDA
submissions, providing a near-term advantage
to our collaborators and customers.”
For Bio-Rad, however, another way to find
the needle in the haystack is simply to make
the haystack smaller.
Rather than try to spot the lone needle in
all that hay, where it might be but one of a
billion or more items, the company’s droplet digital PCR (ddPCR) platform starts by
breaking the haystack up into significantly
smaller stacks. Thus, while most mini-stacks
will only contain hay, a few will contain needles, and those needles will now be a much
higher starting percentage of the overall
mass of the mini-stacks. The needles within
the mini-stacks are then amplified, and the
resulting product is a much higher signal in
a significantly reduced noise.
“I would say that where people are using
ddPCR extensively is in driver mutation and
SPECIAL REPORT
“When you’re talking about non-invasive genotyping—and this is one
big application within the liquid biopsy space—you clearly wouldn’t
want to exclude or ignore one big source of molecular signal. If you
combine captured cfDNA and exoRNA, you essentially get two to four
times the yield than you would just by looking at cfDNA.”
Vince O’Neill, chief medical officer for diagnostics
at Exosome Diagnostics
rare mutation detection, because you can
get such a nice robust reliable measurement
over what they could see prior using perhaps
real-time PCR,” says Paula Stonemetz, director of Diagnostics Business Development at
Bio-Rad.
Stonemetz describes the recent work
of collaborator David Polsky of New York
University in melanoma. In a retrospective ddPCR analysis of blood samples from
former melanoma patients, Polsky was able
to identify changes in the appearance of
BRAF and NRAS mutations anywhere from
four to 16 months before any changes were
detected clinically. Without the ability to
break the samples into smaller aliquots and
enrich the signals, the very slight differences
in DNA sequence would never have been
evident, Stonemetz suggests.
The technology is not only being used to
identify cancer-related mutations, however,
but also changes in methylation patterns
within the analytes. And she says that there
has also been a growing literature of its use
in the identification and analysis of microRNAs, very short molecules (approximately
22 nucleotides) that have significant impact
on gene expression at the post-transcriptional level.
The other predominant method for mutation identification is NGS, and Guardant
Health is not to be outdone when it comes
to the digital sphere. Taking several cues
from the digital communications world,
they developed a platform they call digital
sequencing that they believe addresses three
significant issues with NGS.
The first problem was search space, which
Eltoukhy explains by continuing the haystack
analogy.
“If you only look in 5 percent of the haystack, you’re probably not going to find the
needle,” he says. “It turns out that traditional
NGS technologies, off-the-shelf kits, only
convert about 3 to 5 percent of the DNA that
you start out with into something that makes
its way into the sequencer.”
Thus, the first step they undertook was to
optimize sample processing to ramp that up
to about 90 percent, which he suggests translates directly as increased sensitivity.
The second issue was specificity. As he
explains, although most NGS offer 99.9-percent sequencing accuracy, if you’re looking at
a 10,000-base gene like BRCA1, that translates into 10 false positives per sequencing
experiment. This is where they leveraged the
digital communications angle.
“Just like DSL is able to send bits 1,000times faster over the same copper phone
lines than dial-up modem, you can trade
speed for error rate,” he says. Thus, rather
than getting 1,000-times faster service, you
get 1,000-fold more accurate service. This
they were able to accomplish by precoding
the DNA and recovering all of the molecules
to correct their sequences afterward.
“And then finally, the third piece we had
to get right is to see every type of genomic
alteration in a patient sample,” Eltoukhy says,
including single-nucleotide variants, copy
number variants, gene fusions and insertion-
deletions. “Each class is important because
there are drugs associated with each one that
will help patients quite dramatically.
“The cost of sequencing is not quite
economical yet, but as that continues to
come down, we can imagine doing wholeexome at some point.”
Digital PCR or NGS, the key for companies
like Exosome Diagnostics is to remain open
and flexible to downstream partners and
platforms.
“Essentially, we’re downstream agnostic,”
offers O’Neill. “What we do care about is that
those analytics are optimized for our platform. And again, we’ve done a lot of work
there using things like NGS, digital PCR,
standard qPCR, etc.”
The non-invasion is on
Regardless of the analyte or the analytical
platform, a degree of humility and openmindedness is required going forward, as
no single system will address all scenarios.
As Epic Sciences’ Prahalad reminds us:
“None of us can say yet that we understand
the full range of mutations that cells can
acquire under therapeutic selective pressure
that allow them to remain viable and drive
progression.”
What these platforms and announcements
like QIAGEN’s efforts in Europe do mean,
however, is that liquid biopsy is on the cusp
of transitioning, in Prahalad’s words, “beyond
biologically interesting to clinically actionable.” ■
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www.ddncancer.com
CANCER
RESEARCH
NEWS
A website
for the latest
oncology
news, trends
and resources
■
■
■
■
■
Top cancer-related news
and opinion stories
Archive of all of DDNews
cancer-related news stories
Interviews with key
oncology leaders
Links to various companies,
research centers and
organizations involved
in the field of oncology
and much more!
CLINICAL TRIALS
BRIEFS
Parion expands population
criteria for CF trial
DURHAM, N.C.—Parion Sciences has expanded the
enrollment criteria for its CLEAN-CF study of P-1037
from individuals with cystic fibrosis aged 18 and
above to include individuals with cystic fibrosis
between the ages of 12 and 17 years of age. This
expansion is based on a prespecified safety review
by the Data Monitoring Committee. The CLEAN-CF
study is examining the potential of inhibiting the
epithelial sodium channels in the airways with
P-1037 (also known as VX-371), which is being
developed in collaboration with Vertex Pharmaceuticals. This approach is thought to rehydrate the
mucus layers, thereby improving airway clearance
and potentially lung function. Preclinical models
have shown P-1037 to be long-acting, and Phase
1 studies demonstrated the compound’s safety and
tolerability profile. The launch of the Phase 2 trials
was supported by an award from Cystic Fibrosis
Foundation Therapeutics Inc., the nonprofit affiliate
of the Cystic Fibrosis Foundation.
Abuse-deterrent opioid sees
positive Phase 3 results
CANTON, Mass.—Collegium Pharmaceutical Inc.
recently published results from its Phase 3 clinical
trial of Xtampza ER (oxycodone extended-release
capsules) in opioid-experienced and opioid-naïve
subjects with moderate-to-severe chronic low back
pain. Xtampza ER is an abuse-deterrent, extendedrelease oral formulation of oxycodone developed
with Collegium’s proprietary DETERx technology.
Collegium’s drug was shown to meet the primary
endpoint of a statistically significant difference in
average pain intensity from randomization baseline
to week 12 between the two groups.
IN THIS SECTION
Autoimmune disease
Biogen licenses Mitsubishi’s
MT-1303 for autoimmune diseases........ 29
Cystic fibrosis
Parion expands population
criteria for CF trial................................... 29
Diabetes
Adocia, Lilly advance BioChaperone
Lispro into Phase 1b study...................... 29
HIV/AIDS
Moving forward on HIV........................... 29
Oncology
OSE reports Phase 2
results with Tedopi.................................. 30
Pain/Opioids
Abuse-deterrent opioid
sees positive Phase 3 results.................. 29
Trial costs and timelines
Taking time and money out of
clinical trials (TRIALS from cover) .......... 32
Time keeps on ticking.............................. 32
Biogen licenses Mitsubishi’s
MT-1303 for autoimmune diseases
Potential exists for
development of the
therapeutic in multiple
sclerosis, ulcerative colitis
and Crohn’s disease
BY MEL J. YEATES
CAMBRIDGE, Mass—Biogen has announced
an agreement to exclusively license MT-1303,
a late stage experimental medicine with
potential in multiple autoimmune indications, from Mitsubishi Tanabe Pharma Corp.
(MTPC). MT-1303 is an oral compound that
targets the sphingosine-1-phosphate (S1P)
receptor.
According to MTPC’s website, MT-1303 is
an S1P receptor functional antagonist, and
by inhibiting the receptor function of the
S1P receptor on the lymphocyte, it keeps
lymphocytes sequestered in the lymph nodes
to prevent them from contributing to autoimmune reactions. Due to this mechanism, this
compound may be potentially effective for
various autoimmune diseases. MTPC is currently conducting clinical trials for MT-1303
for multiple sclerosis, psoriasis, Crohn’s dis-
Biogen (pictured here) will pay $60 million up front and as much as $484 million in milestone
payments to Mitsubishi Tanabe Pharma for MT-1303, an oral compound that targets the
sphingosine-1-phosphate receptor.
ease and systemic lupus erythematosus in
Europe and Japan. The compound has also
obtained results suggesting a profile possibly
safer than that of the existing S1P receptor
functional antagonists.
“Based on compelling efficacy and safety
data, we believe that MT-1303 could be a
best-in-class S1P modulator,” said Dr. Alfred
Sandrock, group senior vice president and
chief medical officer at Biogen. “There is a
great need for effective oral therapies for the
treatment of inflammatory bowel disease and
other autoimmune indications, and we are
excited to strengthen our late-stage pipeline
with this next-generation oral investigational
therapy.”
MT-1303 has completed a successful Phase
2 clinical trial for multiple sclerosis, and Biogen is evaluating a rapid development program in this indication. The company will
also investigate indications in inflammatory
MT-1303 CONTINUED ON PAGE 30
Moving Adocia, Lilly advance
forward BioChaperone Lispro
on HIV into Phase 1b study
CytoDyn’s PRO 140, first
self-injectable treatment
for HIV patients, heads to
Phase 3 and could go
commercial by 2017
BY LORI LESKO
The companies will
evaluate the effects of
multiple daily doses of
Adocia’s ultra-rapid insulin
product in type 1 diabetics
BY KELSEY KAUSTINEN
LYON, France & INDIANAPOLIS—A poten-
sing the transmission of human immunodeficiency virus (HIV) while streamlining
patient treatment, biotechnology firm CytoDyn recently reported that its lead candidate
PRO 140 has documented a 98-percent
success rate in a Phase 2b clinical trial. If PRO
140 shows positive results in its upcoming
tial new insulin option is gaining clinical
momentum with the announcement that
Adocia and Eli Lilly and Co. have begun
a Phase 1b clinical trial to evaluate BioChaperone Lispro. Participants in this
study—which will consist of 36 type 1 diabetes patients—will receive multiple daily
doses of BioChaperone Lispro and Hum-
INJECT CONTINUED ON PAGE 34
INSULIN CONTINUED ON PAGE 33
VANCOUVER, Wash.—Targeted toward cea-
There are some weaknesses to the
existing insulin therapies, according to
Gérard Soula, CEO of Adocia, notably that
they need to be injected 15 to 20 minutes
before a meal, something that can be
especially difficult for children with
diabetes. He says BioChaperone Lispro is
designed to have a shorter delay so that
patients can administer the insulin at
mealtime or even after the meal.
CLINICAL TRIALS
OSE reports Phase 2 results with Tedopi
Company unveils
clinical and
immunological
outcomes in
patients with
brain metastases
BY LLOYD DUNLAP
PARIS— OSE Pharma SA, a biotechnology company based in
France that is developing T-specific immunotherapy treatments
against invasive and metastatic
cancers, unveiled some encouraging results of survival and
T-specific immune response in
the patients with brain metastases treated with the company’s
T-specific immunotherapy during
the World Conference on Lung
Cancer, held Sept. 6-9 in Denver.
Organized by the International
Association for the Study of Lung
Cancer, the World Conference
on Lung Cancer (WCLC) is the
world’s largest meeting dedicated
to lung cancer. The event brings
together the world’s lead physicians and researchers to present
the latest breakthroughs and findings in the field.
Six patients identified with
brain metastases had been heavily pretreated; in addition to brain
radiotherapy, they had previously
received from one to three different lines of chemotherapy. The
study of survival under Tedopi
treatment showed a median
survival of 13.75 months, with
extremes ranging from seven
months in a patient whose cancer was still progressing, to a survival exceeding 41 months—this
patient was still alive at the end of
OSE recently reported positive results for its compound Tedopi in patients
with metastatic brain cancer. The most advanced trial right now for Tedopi,
though, is a Phase 3 study in patients with advanced non-small cell lung
cancer who express HLA-A2 and failed first-line therapy.
the study—which are particularly
interesting results for this group
of patients with a poor prognosis.
This study showed a one-year
survival rate for 59 percent of
the group treated with Tedopi.
This compares favorably with the
33-percent one-year survival rate
in patients treated with currently
approved second-line treatments.
The median survival in the group
treated was 17 months, compared
MT-1303
bowel disease. Biogen will initiate a clinical
trial in ulcerative colitis and may advance
an existing program in Crohn’s disease to
Phase 3.
Dr. Kobayashi Tamaki, board director and
managing executive officer of MTPC, tells
DDNews that the Phase 2 trial of MT-1303 for
multiple sclerosis obtained excellent results,
both in efficacy and safety. After using the
effective dose, no bradycardia was observed
that led to clinical concern.
Under the terms of the agreement, Biogen
will receive worldwide rights to MT-1303,
excluding Asia. Biogen will be responsible
for global commercialization and also cover
development costs outside of Asian territories. MTPC will receive an upfront payment
of $60 million from Biogen and may receive
up to $484 million in additional milestone
payments for multiple indications and territories. MTPC has the right to participate in
Biogen’s global clinical trials and has an option to co-promote non-MS indications in the
with 12 months in the group of
patients who did not receive the
treatment. In addition, 25 percent
of patients treated were still alive
after four years, with a good quality of life, which is important for
patients suffering from principally
metastatic tumors.
For five of these six patients, the
study of immune responses showed
that they had actually developed a
specific T cytotoxic response to
United States. The transaction is expected to
close in the fourth calendar quarter of this
year.
According to Zacks Investment Research, adding a S1P receptor modulator to the
pipeline makes sense for Biogen, which has
a strong presence in the multiple sclerosis
market. The successful development of
MT-1303 would also give Biogen the opportunity to diversify into the ulcerative colitis and Crohn’s disease market. However,
MT-1303 is not the only S1P receptor modulator in development. In fact, MT-1303 is a
few years behind Celgene Corp.’s ozanimod,
which is currently in late-stage development
for ulcerative colitis (data expected in 2018)
and relapsing multiple sclerosis (data due
in the first half of 2017). Ozanimod could
well become the first S1P receptor modulator to gain approval for inflammatory
bowel diseases. Ozanimod could also have
an advantage over existing treatments if it
is able to maintain its previously demonstrated cardiac, hepatotoxicity and lymphocyte
recovery profile.
In other recent Mitsubishi Tanabe Pharma
at least one, and up to five, of the
tested epitopes included in Tedopi.
An international patent application
on this particular clinical domain
was filed in November 2014.
“We are particularly pleased that
these very encouraging results have
been presented in the form of a poster at this prestigious conference,
with Dr. John Nemunaitis, oncologist and executive medical director of the Mary Crowley Cancer
Research Centers in Dallas, as
our main author. This new data
confirm the potential of Tedopi’s
clinical development, which will
now continue with the launch of its
pivotal Phase 3 trial,” said Dr. Alain
Chatelin, chief medical officer at
OSE Pharma.
OSE Pharma is a European
cancer immunotherapy company
with a multi-epitope technology
named Memopi that directs the
body’s immune system to generate
a specific cytotoxic T response to
prevent cancer cell growth.
OSE Pharma’s lead product,
Tedopi, combines 10 “neo-epitopes” directed against five tumorassociated antigens selected
because their presence is linked to
a poor prognosis and the severity
of various cancers. These neoepitopes generate strong specific
T cytotoxic responses that fight
cancer and prevent tumor escape.
In its most advanced application,
it is about to enter a pivotal Phase
3 study in patients with advanced
non-small cell lung cancer
(NSCLC) who express HLA-A2
and failed first line therapy. Tedopi
has orphan drug status in the U.S.
and is considered as personalized
medicine in Europe in HLA-A2
positive patients.
OSE Pharma is also planning a
new Phase 2 clinical trial in com-
bination with another immunotherapy treatment in NSCLC. Also,
OSE Pharma plans a Phase 3 clinical program in 2015 in Europe and
the United States in order to obtain
registration in NSCLC. The study
will recruit patients with invasive/
metastatic NSCLC expressing the
HLA-A2 receptor (45 percent of the
NSCLC population).
OSE Pharma is currently preparing to start a Phase 3 study of
Tedopi. The trial protocol is common to Europe and to the United
States. The launch of the Phase 3
study of Tedopi is planned for the
second half of 2015. It will look to
enroll 500 patients with invasive/
metastatic NSCLC expressing the
HLA-A2 receptor. Tedopi will be
used as a second-line treatment for
patients for whom first-line treatments (such as chemotherapy)
have not been able to control their
disease. Preparatory work and manufacturing of the clinical supplies
have started. An agreement had
been signed in January 2015 with
Orion-Symbec, a contract research
organization based in Great Britain, for this international Phase 3
study.
Lung cancer is the deadliest
cancer in the world. In 2012, there
were 1.58 million new diagnosed
lung cancer cases and 1.39 million
deaths from this disease globally.
Despite the different treatments
available today (surgery, radiotherapy, chemotherapy, targeted
therapy), the relative survival rates
of these patients at metastatic stage
remains very low. Given the large
incidence of NSCLC, OSE Pharma
estimates that the potential global
sales at peak for Tedopi for this
single indication could be about
€2 billion, or about $2.24 billion. n
“We believe that MT-1303 could be a best-inclass S1P modulator. There is a great need for
effective oral therapies for the treatment of
inflammatory bowel disease and other
autoimmune indications, and we are excited to
strengthen our late-stage pipeline with this
next-generation oral investigational therapy.”
Dr. Alfred Sandrock, chief medical officer of Biogen
news, the company recently completed a
deal with Regeneron Pharmaceuticals Inc.
to acquire exclusive development and commercialization rights for fasinumab in Japan,
Korea and other Asian countries, excluding
China. Fasinumab is an antibody that specifically binds to nerve growth factor, which is
believed to play a role in pain. In a Phase 2
clinical study regarding osteoarthritis in the
United States, fasinumab demonstrated the
ability to promptly ameliorate moderate-tosevere pain. A Phase 2b/3 study for pain due
to osteoarthritis was initiated in mid-2015 in
the United States as well. As a result of this
agreement, the two companies plan to move
ahead with the development of fasinumab
in Japan for indications of musculoskeletal
pain, specifically osteoarthritis and chronic
low back pain. n
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CLINICAL TRIALS
TIME KEEPS ON TICKING
Cycle time reduction
remains elusive,
according to KMR
Group’s annual cycle
time trends analysis
CHICAGO—KMR Group, a leader in analyz-
ing research and development performance
data for the biopharmaceutical industry,
reported in August that the duration of
clinical trials continues to hold steady or
increase, despite ongoing efforts by biopharmaceutical companies to reduce cycle
times. Specifically, KMR assessed cycle time
trends for more than 6,000 Phase 2/3 clinical trials using proprietary industry data
across 27 companies going back to 2005.
The analysis focused on clinical trials across
all therapeutic areas.
KMR defines total cycle time as the interval from protocol approval to clinical trial
report, and the analysis reportedly reveals
that both Phase 2 and 3 trials have increased
significantly over the last 10 years; moreover, they are continuing to rise. Phase 3
trials took a median 35.7 months in 20052007 and 42.9 months in 2012-2014. Not
only have industry median cycle times risen,
KMR notes, but also when normalizing performance by company, the median change
on a company basis also shows significant
increases. Since the 2005-2007 period,
cycle times have increased 16.4 percent in
Phase 2 and 55.4 percent in Phase 3 on a
per-company basis.
Despite efforts to reduce data capture time and otherwise streamline clinical trials, cycle times
continue to increase thanks to such factors as regulators and payers demanding more from
companies to demonstrate safety, efficacy and cost effectiveness.
“One obvious question is why, despite
efforts to reduce time, cycle times continue to rise,” KMR noted in observing these
trends. “Only with this understanding can
companies set actionable controls to help
counteract this negative trend.
“We see the research environment shifting
as regulators and payers demand more from
companies to demonstrate safety, efficacy
and cost effectiveness. The result of these
shifts are increasing patient sample sizes,
longer treatment times and more carefully
observed adverse effects. Indeed, a major
factor as to why cycle times have risen are
increasing treatment times in the trial deign.
However, even when accounting for treatment time, there is still a large increase in
study duration over this time frame, indicating treatment alone is not the cause.”
Another dynamic brought on by these
growing demands is the increased use of contract research organizations to offload some
of the rising burden. That shift itself brings
an entirely new set of challenges, such as how
ArQule presents additional
clinical biomarker data from
Phase 2 study of tivantinib
in hepatocellular carcinoma
BURLINGTON, Mass.—ArQule Inc. announced in September
that additional analyses of plasma biomarkers support the
prognostic and predictive role of MET status in a previously
reported Phase 2 trial in hepatocellular carcinoma (HCC)
involving tivantinib, an orally administered, selective inhibitor of MET, a receptor tyrosine kinase. The Phase 2 study,
completed in the third quarter of 2011 and published in The
Lancet Oncology medical journal in November 2012, enrolled
107 HCC patients who progressed or were intolerant to one
prior systemic therapy. Multiple biomarkers were evaluated as part of the study, and MET status as determined by
immunohistochemistry emerged as the strongest predictor
of tivantinib benefit. In addition, the presentation noted that
biopsies were more likely to be categorized as MET-high
when taken after sorafenib therapy than before therapy.
“The biomarker data from this trial demonstrates that
patients with MET-high tumors are more likely to benefit
from tivantinib therapy,” said Dr. Brian Schwartz, head of
research and development at ArQule. “On the basis of the
results from the Phase 2 trial and in partnership with Daiichi
Sankyo, we are conducting the pivotal Phase 3 METIV-HCC
trial that is enrolling MET-high HCC patients as determined
by a required companion diagnostic test.”
By the end of 2015 the pivotal Phase 3 trial, METIV-HCC,
is expected to complete enrollment of approximately 300
patients, randomized 2:1 treatment to best supportive care,
with the primary endpoint of overall survival.
Globally, liver cancer is the sixth most common cancer
and is the second-leading cause of cancer related death.
HCC accounts for about 90 percent of primary liver cancers.
Preclinical data have demonstrated that tivantinib inhibits
MET activation in a range of human tumor cell lines and
shows antitumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has
been generally well tolerated and has shown clinical activity
in the tumors studied. Tivantinib has not yet been approved
for any indication in any country.
In December 2008, ArQule and Daiichi Sankyo signed a
license, co-development and co-commercialization agreement for tivantinib in the U.S., Europe, South America and
the rest of the world, excluding Japan, China (including Hong
Kong), South Korea and Taiwan. n
best to manage the CRO relationships, oversight, loss of operational control and quality
concerns—and still keep costs low.
As the pharma and biotech industry
evolves to a more patient-centric view and
the investment in personalized medicine
(such as biomarkers and companion diagnostics) and rare diseases becomes more important, KMR expects trial times to continue to
increase—it also expects further demand
from regulators to incorporate payer-specific endpoints in trial design, which will add
complexity, cost and time.
Electronic data capture (EDC) systems
have been one tool companies have used to
reduce cycle times, and KMR notes that over
the past decade, the use of EDC to reduce
data capture times has had a positive impact
for companies. But, as most companies have
already transitioned to EDC in a majority of
trials, KMR maintains that the next frontier
in terms of reducing cycle times is in the
study start-up and recruitment space.
“This encompasses an entire set of processes that can contribute to lengthy cycle
times, such as country startup, site initiation
and the performance of sites, as well as the
specific countries companies are working in
and how many,” KMR notes. “If companies
focus on this area, they can achieve substantial reductions in trial time, but navigating
the dynamic between major and emerging
markets, site performance and size of study
is a complex endeavor. Companies that
maneuver this area with more dexterity will
be able to achieve large improvements, but
companies that are unable to meet the rising
demand and challenging environment from
regulators and payers will continue to fall
behind the industry.” n
TRIALS
vision for using industry-leading technologies and real-world
data sets to improve clinical
development.”
“Clinical trials are crucial in the
drug and treatment development
process, but when it comes to
identifying appropriate trial
candidates, there are significant
data challenges, which can
contribute to delays for bringing new therapies to market,”
according to Sean Hogan, vice
president and general manager of
IBM Healthcare. “Through cognitive computing and cloud-based
data, our goal is to help our clients accelerate the time it takes to
complete clinical trials and reach
conclusive trial results.”
Watson is the first commercially available cognitive computing
capability that is said to represent a
new era in computing. The system,
delivered through the cloud, analyzes high volumes of data, understands complex questions posed
in natural language and proposes
evidence-based answers. Watson
continuously learns, gaining in
value and knowledge over time
from previous interactions. In April
2015, the company launched IBM
Watson Health and the Watson
Health Cloud platform. The new
unit will help improve the ability
of doctors, researchers and insurers to innovate by surfacing new
insights from the massive amount
of personal health data being created daily. The Watson Health
Cloud allows this information to be
de-identified, shared and combined
with a dynamic and constantly
growing aggregated view of clinical, research and social health data.
ICON plc is a global provider of
drug development solutions and
services to the pharmaceutical,
biotechnology and medical device
industries. The company specializes in the strategic development,
management and analysis of
programs that support clinical
development—from compound
selection to Phase 1-4 clinical studies. At any given time, the company
supports 120 to 130 oncology trials
simultaneously. With headquarters
in Dublin, Ireland, ICON currently
operates from 81 locations in 37
countries and has approximately
11,300 employees. n
CLINICAL TRIALS
Eli Lilly (pictured here) and
Adocia recently launched
a Phase 1b clinical trial
to examine the effects of
multiple daily doses of
Adocia’s BioChaperone
Lispro, an ultra-rapid
insulin injection,
when administered at
or after mealtime.
INSULIN
alog (insulin lispro rDNA origin)
over two periods of 14 days each,
either at mealtime or 15 minutes
after the meal. Adocia will sponsor
the study, which will be performed
by Profil Neuss in Germany. While
the main objective is to compare
post-meal glucose profiles after
identical bolus injections of either
BioChaperone Lispro or Humalog
relative to a solid meal stimulus,
the study will also evaluate the
safety and efficacy of an ultra-rapid
insulin absorption profile in an outpatient setting.
“This new clinical study aims
to further document the potential
benefit of BioChaperone Lispro,”
said Olivier Soula, research and
develolment director and deputy
general manager of Adocia. “We
continue to move rapidly to characterize the clinical effects of the
ultra-rapid insulin lispro profile
and prepare the product for Phase
3 clinical testing.”
BioChaperone Lispro is an
ultra-rapid formulation of insulin lispro licensed to Lilly and
formulated using Adocia’s proprietary technology BioChaperone,
which is designed to accelerate
insulin absorption. There are
some weaknesses to the existing
insulin therapies, says Gérard
Soula, CEO of Adocia, primarily the fact that they need to be
injected 15 to 20 minutes before
a meal, as “there is a delay after
injection before insulin can reach
the blood circulation.” This can
be especially difficult to deal with
in the case of children who are
diabetic, he notes.
“The purpose of this formulation
is to have a shorter delay, in order
that the patient can administer the
insulin at the mealtime or even
after the meal,” Soula tell DDNews.
He notes that Lilly stood out as
an ideal partner for this work due
to its experience in the diabetes
market—and of course, with
Humalog—as well as its knowledge
of the process for introducing a
new insulin formulation.
Lilly and Adocia inked a worldwide licensing collaboration to
develop BioChaperone Lispro for
individuals with type 1 and type 2
diabetes in December 2014. Per
the terms of the agreement, Lilly is
responsible for future development,
manufacturing and commercialization of BioChaperone Lispro.
Adocia will receive $50 million in
an upfront fee, with the potential
for future payments of up to $280
million if certain development
and regulatory milestones are met
and up to $240 million in sales
milestones payments, as well as
tiered sales royalties. Lilly will
reimburse Adocia for certain research and development expenses,
and a concentrated formulation
of BioChaperone Lispro is also
included in this agreement.
“An ultra-rapid acting insulin, if
CREDIT: ELI LILLY AND CO.
approved by regulators, could provide a new important treatment
option for people with type 1 and
type 2 diabetes,” Enrique Conterno,
president of Lilly Diabetes, said in
a press release announcing the
alliance. “An ultra-rapid acting
insulin would be a natural fit in
our growing portfolio.”
The first study in this partnership was a Phase 1b trial, which
was initiated in January of this year
with the goal of looking at the effect
of Humalog and BioChaperone
Lispro, injected at the time of
a meal, on post-meal glycemic
control in type 1 diabetics. Adocia
and Lilly announced the study’s
completion in July as well as the
positive results from the trial.
BioChaperone Lispro produced
a 61-percent reduction in postprandial glucose excursion over
the first two hours compared to
Humalog. This matched previous
clinical findings from another trial
that found that BioChaperone
Lispro has a significantly faster
rate of insulin lispro absorption
than Humalog, with an increase
in the early insulin exposure of
168 percent. Both drugs led to
similar numbers of hypoglycemia
episodes, and no local reactions
were seen at the administration
sites for either one.
Further Phase 1b clinical studies
are planned for this year to better
understand the drug’s performance
for additional diabetic patient
needs. n
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9/25/2015 8:11:45 AM
CLINICAL TRIALS
INJECT
“We believe our treatment
substitution study has the
potential to provide a drug
holiday to patients from their
daily pill regimen,” says Dr. Nader
Pourhassan, president and CEO
of CytoDyn. “PRO 140 could be
the key to maintaining viral load
suppression in the absence of
pills. If the [Phase 3] study has a
positive outcome, we believe this
may address a significant unmet
medical need and have high
patient acceptance.”
Phase 3 trial, the first self-injectable antibody
for HIV could go commercial in 2017—and
vastly change the way HIV patients take their
medicine.
The National Institutes of Health (NIH)
has shown its faith in PRO 140 by providing more than $28 million in grants for the
development of the antibody. More than 1.2
million individuals are infected with HIV
in the United States, with new infections
surpassing 50,000 annually; an estimated
25 percent are unaware of their infection.
Worldwide, 36 percent of the population
need antiretroviral therapy, with 33.4 million infected individuals and 2.7 million new
infections per year.
“Results from six Phase 1 and Phase 2
human clinical trials have shown that PRO
140 can significantly reduce viral load
in people infected with HIV,” Dr. Nader
Pourhassan, CytoDyn president and CEO,
stated in an August 18 news release. “Our
Phase 3 protocol provides for an upcoming 25-week study with 300 HIV-positive
patients. Selection of clinical sites, IRB
approvals, patient screening and other
administrative matters are underway and
expected to be completed in time for the
first patient (in Phase 3) to be dosed in the
third quarter of this year.”
Pourhassan tells DDNews that if approved,
PRO 140 could serve as a substitute to the
current HIV patient drug regimen of swallowing “anywhere from seven to 35 pills per
week or taking from one to five pills a day.”
PRO 140 has been successful in the previous
Phase 2 trial using only the injectable to treat
the disease and not allowing HIV patients to
take their pill regimen.
“We believe our treatment substitution
study has the potential to provide a drug
holiday to patients from their daily pill
regimen,” Pourhassen said. “PRO 140
could be the key to maintaining viral load
suppression in the absence of pills. If the
[Phase 3] study has a positive outcome,
we believe this may address a significant
unmet medical need and have high patient
acceptance.”
Pourhassan wouldn’t go as far as calling
PRO 140 a miracle drug, but “Considering PRO 140 has almost no toxicity or side
effects, having the FDA acknowledge this fact
in a letter to us and giving PRO 140 a fasttrack status, I would say this product could
make millions of HIV patients’ quality of life
much better,” Pourhassan says. “CytoDyn
purchased PRO 140 from Progenics more
than 12 years ago, developing this product
Advaxis’ axalimogene
filolisbac shows mettle against
metastatic cervical cancer
PRINCETON, N.J.—Advaxis Inc., a biotechnology
company developing cancer immunotherapies,
and the Gynecologic Oncology Group (GOG, now
part of NRG Oncology), recently announced clinical data from stage 1 of an ongoing two-stage
Phase 2 study (GOG-0265) of Advaxis’s lead Lm
Technology immunotherapy, axalimogene filolisbac (ADXS-HPV), in patients with persistent or
recurrent metastatic (squamous or non-squamous
cell) carcinoma of the cervix (PRmCC) who have
progressed on at least one prior line of systemic
therapy. The stage 1 data showed that treatment
with axalimogene filolisbac resulted in a 38.5 percent 12-month overall survival rate in 26 patients.
Evaluation of safety data showed that grade
1 or 2 adverse events occurred in 19 out of 26
patients (73 percent), with fatigue, chills and
fever being the most common. Four patients (15
percent) experienced a grade 3 adverse event
(hypotension and cytokine release syndrome)
and one patient (4 percent) experienced a grade
4 adverse event (lung infection and sepsis).
“Patients with PRmCC who have failed at least
one line of therapy face a life-threatening condi-
tion with an estimated survival of four to seven
months and no available treatment options,” said
Dr. Tom Herzog, clinical director at the University
of Cincinnati Cancer Institute. “The stage 1 results
for axalimogene filolisbac, which show 12-month
survival, are a meaningful step forward in meeting the needs of women who require second-line
treatment for PRmCC.”
The GOG has conducted over 17 studies of a
diverse set of investigational agents and regimens,
but never has the 12-month overall survival rate
exceeded 30 percent in people with PRmCC. Stage
2 of the GOG-0265 study is currently enrolling and
the protocol has been amended by GOG to allow
for continuous cycles of treatment until disease
recurrence (the stage 1 protocol provided for three
doses of axalimogene filolisbac over 3 months).
“The axalimogene filolisbac data presented
at AGOS by the GOG and Dr. Herzog represent
some of the most encouraging Phase 2 data to
date in metastatic cervical cancer and support
the results previously observed in Advaxis’ own
Phase 2 study,” said Daniel J. O’Connor, president
and CEO of Advaxis. n
and receiving over $28 million from the NIH
due to all the spectacular results PRO 140
kept getting.”
PRO 140 works by blocking the HIV coreceptor CCR5 on T cells, preventing viral
entry, while effectively reducing viral loads
by as much as 1.8log with one dose per week,
according to CytoDyn. If the HIV patient’s
viral load is completely suppressed, the transmission rate becomes almost zero.
The transmission of HIV, a highly infectious disease, “goes to almost zero when the
viral load reaches a complete suppressed
level,” Pourhassan notes. “PRO 140 can
and has demonstrated keeping the viral
load suppressed in HIV patients without
taking pills.”
In the Phase 2b study, CytoDyn’s primary
objective was to assess the efficacy of PRO
140 monotherapy for the maintenance
of viral suppression in HIV patients who
are stable on combination antiretroviral
therapy, known as HAART (highly active
antiretroviral therapy), but need or wish to
discontinue HAART therapy temporarily,
Pourhassan explains.
About 85 percent of the patients who are
HIV positive in the United States and are not
very experienced in treatment have a strain of
HIV that is called R5, he adds. The R5 strain
binds to CCR5 in order to enter the CD4 cell.
However, the other 15 percent mostly have a
small amount of X4 virus in addition to R5,
which is called dual/mix virus. PRO 140 does
not work on dual/mix viruses.
“Globally, HIV transmission rate is high,”
Pourhassan says. “We definitely think PRO
140 can help decrease those numbers. Our
long-term goal is for PRO 140 only to provide
monotherapy for all HIV patients who are
R5 exclusive.”
Phase 3 trials are expected to be conducted
in more than 30 U.S. sites. The company
plans to submit its New Drug Application for
final approval of PRO 140 in November 2016.
PRO 140’s previous fast-track designation
carries a possibility of accelerated approval
for the injectible.
A once-a-week dose of two PRO 140 shots,
“one in each thigh, or possibly a once-amonth dose, can control their HIV patients’
viral loads enough to lead a fairly normal life,”
Pourhassan says. “We are very encouraged
with the success of prior PRO 140 studies
and expect excellent Phase 3 results. When
an HIV patient’s viral load is completely
suppressed, the transmission rate becomes
almost zero, allowing the return to a normal
life. PRO 140 may become a commercial
product in 2017.” n
WCG and PCCTC announce
new partnership to
improve efficiency of
oncology research reviews
PRINCETON, N.J. & NEW YORK—WIRB-Copernicus Group (WCG), a global provider of regulatory and ethi-
cal review services and software to support clinical research, and the Prostate Cancer Clinical Trials
Consortium (PCCTC), a leading multicenter clinical research organization specializing in cutting-edge
prostate cancer research, have formed a new partnership to enhance the quality and efficiency of the
consortium’s research review process.
PCCTC joins many of the nation’s other prominent cancer research institutions in relying on WCG
for the review of its cancer research protocols and related study documents. WCG Oncology, WCG’s
cancer-focused division, is comprised of experts who specialize in oncological subspecialties and
advise WCG’s three cancer-focused institutional review board (IRB) panels on the science behind
cutting-edge therapies.
“We are delighted to provide PCCTC with the confidence that its research will be reviewed with
the appropriate expertise and therapeutic focus, and in a timely and efficient manner. The consortium
is doing sterling work in exploring cutting-edge science, and we are proud to facilitate the conduct of
its important clinical research,” commented WCG Chairman and CEO Dr. Donald A. Deieso.
The partnership with WCG represents a significant change for PCCTC, which previously relied on
its members’ local IRBs. That approach had resulted in several IRBs being required to approve the
protocol, participant consent and other documents for a single study, leading to inconsistencies and
unnecessary delays.
“The PCCTC is excited to collaborate with WCG to provide a more efficient and more thorough model
for reviewing prostate cancer research,” said PCCTC CEO Jake Vinson. “We have conducted our first
clinical study using WCG, and have already gained efficiencies by reducing administrative delays and
eliminating the redundancy of multiple, uncoordinated reviews.” n
DIAGNOSTICS
GeneCentric highlights LSP 120
at lung cancer conference
DURHAM, N.C.—This year’s World Conference on
Lung Cancer, held in Denver in early September,
saw GeneCentric Diagnostics Inc. present new
data on LSP 120, its lung cancer subtyping product,
which was developed using the company’s Cancer
Subtyping Platform. The presentation was titled
“Survival Differences of Adenocarcinoma Lung
Tumors with Squamous Cell Carcinoma or Neuroendocrine Profiles by Gene Expression Subtyping,”
and Dr. Hawazin Faruki, vice president for clinical
development at GeneCentric, served as presenter.
“LSP 120 has the potential to identify a
subset of lung adenocarcinoma patients with
poor prognosis, as compared to other lung
adenocarcinoma patients,” said Faruki. “Reduced
survival may be due to inherent features of the
tumor and to variable response to standard lung
adenocarcinoma therapeutic management. LSP
120 subtyping may prove to be an important tool
in stratification strategies for improved drug trial
design and patient care.”
Mobidiag links with
Unilabs in Amplidiag deal
ESPOO, Finland & GOTEBORG, Sweden—A supply agr-
eement was recently announced between diagnostics companies Mobidiag Ltd. and Unilabs.
Though no financial details were released, the agreement covers the supply of Amplidiag products
for Unilabs in Sweden and Norway over the next
four years. The Amplidiag product line includes six
diagnostic products for gastrointestinal infections,
including tests for gastroenteritis, carbapenemand vancomycin-resistance screening and noninvasive Helicobacter pylori testing.
“Molecular diagnostics is gaining traction and
becoming an increasingly important tool in improving patient diagnostics,” remarked Dr. Helena
Enroth, responsible for R&D in molecular microbiology at Unilabs Sweden. “Implementing new multiplex molecular diagnostic tools is a step forward
in our efforts to continuously improve our service
portfolio and meet customer demands. Mobidiag is
able to offer a comprehensive suite for gastrointestinal testing, and importantly, the products meet
our expectations for large-scale use.”
IN THIS SECTION
Gastrointestinal/Molecular Dx
Mobidiag links with Unilabs
in Amplidiag deal.................................... 35
Microbiology
Roche acquires GeneWEAVE.................. 35
Oncology
A pan-Pacific partnership........................ 36
GeneCentric highlights LSP 120
at lung cancer conference....................... 35
Muddy waters for cancer detection?...... 35
Roche acquires GeneWEAVE
GeneWEAVE’s Smarticles
technology enhances
Roche’s diagnostics
role in fighting
drug-resistant bacteria
CREDIT: ROCHE
BRIEFS
BY LLOYD DUNLAP
BASEL, Switzerland— Roche has signed a
definitive agreement to acquire GeneWEAVE
BioSciences Inc., a privately held company
focused on innovative, clinical microbiology
diagnostics solutions based in Los Gatos, Calif.
Under the terms of the agreement, Roche will
pay GeneWEAVE shareholders $190 million
up front and up to $235 million in contingent
product-related milestones. The transaction is
subject to customary closing conditions and,
once closed, GeneWEAVE will be integrated
into Roche Molecular Diagnostics.
The acquisition provides Roche with
GeneWEAVE’s Smarticles technology, an
innovative class of molecular diagnostics
that quickly identifies multidrug-resistant
Roche (pictured here) will acquire GeneWEAVE BioSciences Inc., a California company focused
on innovative, clinical microbiology diagnostics solutions, for as much as $425 million.
organisms (MDROs) and assesses antibiotic
susceptibility directly from clinical samples,
without the need for traditional enrichment,
culture or sample preparation processes.
GeneWEAVE’s first system in development
is the vivoDx, a fully automated, randomaccess system designed to meet the needs of
laboratories addressing MDRO detection and
antibiotic therapy guidance. The technology
is currently being evaluated in multiple sites
across the U.S. In the presence of antibiotics,
susceptible bacteria targeted by Smarticles
will remain dark, while drug-resistant bac-
teria produce light quickly and efficiently.
A DNA molecule designed by GeneWEAVE
causes the bacteria to express luciferase, a
molecule that produces light.
According to GeneWEAVE’S documented results, among 153 patients Smarticles
reduced the time to therapy from 81 to 23
hours, reduced hospital stays by 34 percent
and mortality by more than 50 percent.
“With GeneWEAVE, we further strengthen our microbiology diagnostics offerings
with cutting-edge technology that will aid
GENEWEAVE CONTINUED ON PAGE 36
MUDDY WATERS FOR
CANCER DETECTION?
Study of multigene panel raises
questions about heredity risk of
breast and ovarian cancer
BY LORI LESKO
SAN FRANCISCO—After watching her 33-year-old
“Our study is distinguished from
previously published work by the
size of our cohort together with
the availability of detailed
personal and family history data
collected directly from involved
participants,” wrote the authors
of a JAMA Oncology paper
recently on multigene testing, of
which Stanford University
(pictured here) was a part. “In
addition, our study avoids biases
inherent in studies conducted
exclusively on samples available
to genetic testing laboratories
because our participants were all
enrolled directly at the site of
referral under uniform criteria.”
mother and 39-year-old aunt battle breast cancer,
Amanda Burris, 23, was tested at Invitae Corp. for
genetic markers BRCA1 and BRCA2.
The results, like that of her grandmother, mother and aunt, came back
positive—thus, significantly increasing
her risk of developing breast cancer.
Rather than pity herself, the college
student went into action, pumping up
her cancer-prevention measures like scheduling an
annual MRI rather than a mammogram and having
children sooner than later before possibly opting
for a mastectomy.
“Getting genetic testing really helped because
we have a plan and now we understand our options
better,” Burris stated on the Invitae website, Patient
Stories. “It’s all about taking back control of my
life.”
Invitae and collaborators announced this summer the publication of new data describing the
clinical actionability of multigene testing for
hereditary breast and ovarian cancer (HBOC) risk
in JAMA Oncology. The study was a collaboration
among Massachusetts General Hospital, Harvard
Medical School, Stanford University, Beth Israel
Deaconess Medical Center and Invitae.
Surprisingly, the study found that multigene
testing of women negative for BRCA1 and BRCA2
revealed some of them harbored other
harmful genetic mutations, most commonly moderate-risk breast and ovarian
cancer genes and Lynch syndrome genes,
which increase ovarian cancer risk.
Multigene panel genetic tests are
increasingly recommended for patients
evaluated for a predisposition to HBOC. However,
the rapid introduction of these tests has raised concerns because many of the tested genes are low- to
moderate-risk genes for which consensus management guidelines have not been introduced or which
were introduced only very recently.
In the beginning, more than 1,000 patients
were tested with multigene panels, and the clinical actions that would be considered were reviewed
for all patients testing positive for cancer genes
TOOLS &
TECHNOLOGY
MULTIGENE CONTINUED ON PAGE 37
DIAGNOSTICS
A PAN-PACIFIC PARTNERSHIP
Burning Rock,
Illumina ink
molecular
diagnostics deal
BY KELSEY KAUSTINEN
mina Inc. and Burning Rock, a diagnostics
company focused on molecular testing for
the improvement of individualized treatment
guidance for cancer patients, are joining forces in a newly announced agreement, under
which Burning Rock will develop advanced
clinical applications for molecular diagnostics in oncology based on Illumina’s nextgeneration sequencing (NGS) technology.
This collaboration will seek to offer the
most advanced, integrated sequencing
solutions for the clinical market by uniting
Illumina sequencing technology with the
advanced clinical application development
capabilities of Burning Rock. A particular
focus will be the development of a userfriendly, oncology molecular diagnostic kit
for the Chinese market. Under
this agreement, the first between
the two organizations, Burning
Rock will provide its nucleic acid
extraction, library preparation
and data analysis software, with
Illumina providing NGS instrument components and related reagents. No
additional details for the deal were made
available.
“We have been working to promote the
clinical application of genomic technology in
China. Oncology molecular diagnosis based
on NGS, including non-invasive testing, is
being applied in the clinic, and we hope to
promote it as a standard practice in hospitals.
As the leader in oncology molecular diagnosis, Burning Rock is now very pleased to
partner with Illumina, the global leader in
sequencing and array-based technologies.
Cooperation between our two companies
will provide additional high-quality molecular diagnostic solutions in the clinical field of
CREDIT: ILLUMINA INC.
GUANGZHOU, China & SAN DIEGO—Illu-
Although it would not provide details on the specific technologies or platforms involved,
Illumina recently inked a deal to unite its sequencing technology with the advanced clinical
application development capabilities of China-based diagnostics company Burning Rock.
oncology,” commented Yusheng Han, founder and CEO of Burning Rock, in a statement
regarding the agreement.
Burning Rock’s state-of-art molecular
and pathological examination platform
features NGS, qPCR, immunohistochemistry, fluorescence in-situ
hybridization and digital pathology. John Leite, vice president of
oncology at Illumina, comments
that Burning Rock “brings capabilities in designing and validating
panels, and also in creating accompanying
databases” to the collaboration.
“As the number of targeted therapeutics
in oncology expands, so does the number of
genes that require genetic analysis,” Leite
says of the need for more diagnostic options.
“Laboratories struggle to develop diagnostic
molecular tests on a single platform that
can scale to their needs. Next-generation
sequencing offers multiplex capability from
a single gene to thousands, can detect sequence variants, structural and copy number
variants, as well as differential mRNA
expression capability.”
Illumina declined to comment on which
of its technologies would be focused on in
TOOLS &
TECHNOLOGY
GENEWEAVE
in the fight against drug-resistant bacteria.
This technology has the potential to provide
healthcare professionals access to quick
and accurate diagnoses that can lead to
rapid, informed treatment decisions,” said
Roland Diggelmann, chief operating officer
of Roche Diagnostics. “We welcome GeneWEAVE’s employees, who will continue to
focus on the development and manufacturing of diagnostics solutions based on the
Smarticles technology.”
“We are very excited to continue
developing innovative microbiologic diagnostics solutions as part of the Roche
Molecular Diagnostics team,” said Steve
Tablak, CEO of GeneWEAVE. “Roche is the
ideal company to deliver on the promise
of our Smarticles technology. We are fully
committed to the continued success of
GeneWEAVE’s employees, products and
pipeline.”
Dan Leonard, an analyst at Leerink
Research, states that “We believe Roche’s
acquisition of GeneWEAVE Biosciences
validates the value in rapid microbiology testing, specifically testing for drugresistant bacteria.” Leonard goes on to list
four other market participants for whom
Leerink considers the Roche move a validation: Cepheid Inc., an American molecular diagnostics company that develops,
manufactures and markets fully integrated
systems for testing in the clinical market
and for application in its original nonclinical market; Accelerate Diagnostics Inc.,
an in-vitro diagnostics company dedicated to providing solutions for the global
challenge of drug resistance; OpGen, a
diagnostics company helping to combat
and control life-threatening multidrugresistant organisms using DNA testing and
bioinformatics tools; and T2 Biosystems.
“In particular,” Leonard adds, “the price
tag supports our view that TTOO’s [T2
Biosystems] platform value is currently
underappreciated by the Street. GeneWEAVE boasts an ability to detect drug-
this agreement, but there is no shortage of
options to choose from. Illumina’s MiSeq System offers an ideal solution for sequencing
targeted panels, amplicons and small
genomes. The MiSeqDx System was designed
specifically for clinical laboratories, and is
the first U.S. Food and Drug Administrationcleared in-vitro diagnostic NGS system. The
company’s NextSeq 500 System combines
high-throughput sequencing with the simplicity of desktop sequencers, while the
HiSeq 2500 System enables large-scale
high-throughput exome, transcriptome
and whole-genome sequencing projects.
Illumina’s HiSeq X Ten, according to the
company, “is the first sequencing platform
that breaks the $1,000 barrier for a 30x
human genome.”
Illumina’s NGS differs from the classic
Sanger chain-termination method; instead, Illumina’s tech applies sequencing
by synthesis technology, which tracks the
addition of labeled nucleotides as the DNA
chain is copied, in a massively parallel
fashion.
“Illumina is very excited to collaborate
with Burning Rock to increase access to
oncology diagnosis solutions in China,” Dr.
Rick Klausner, senior vice president and
chief medical officer of Illumina, said in a
news release. “We are committed to partnering with Chinese companies who share
our vision of improving human health by
unlocking the power of the genome.”
Indeed, this is the second diagnostic agreement with a Chinese partner for Illumina
this summer. On June 10, the company
announced that, together with Beijing-based
Annoroad, it would be jointly developing
advanced clinical applications for reproductive health based on NGS technology. The
two will work together on the development
of a user-friendly, prenatal DNA diagnostic
system for the Chinese market, uniting Illumina’s sequencer technology with Annoroad’s
advanced clinical application development
capabilities. n
“As the number of targeted therapeutics in
oncology expands, so does the number of genes
that require genetic analysis ... Next-generation
sequencing offers multiplex capability from a
single gene to thousands, can detect sequence
variants, structural and copy number variants, as
well as differential mRNA expression capability.”
John Leite, vice president of oncology at Illumina
resistant bacteria directly from a sample
of interest, without the need for an intermediate culturing step. This value proposition sounds similar to that of TTOO’s.
Unknown to us is whether this technology would allow comparable sensitivity to
TTOO, which has a lower limit of detection of one colony forming unit (CFU)/
mL, or whether the technology can test for
multiple organisms in the same sample.”
At minimum, Leonard noted, Leerink
believes T2 Biosystems’s $260-million market cap “looks even more compelling” next
to the $425-million price for GeneWEAVE.
GeneWEAVE works to advance clinical
microbiology with diagnostic solutions
to aid healthcare providers in the fight
against drug-resistant bacteria by enabling
“impactful surveillance programs, early
therapy guidance and successful antibiotic stewardship.” The company’s proprietary Smarticles technology is designed
to rapidly detect drug resistance and
measure susceptibility information without the need for enrichment, culture or
sample preparation. The company refers
to this new paradigm as “Sample-In/
Susceptibility-Out.”
Roche, a leader in research-focused
healthcare with combined strengths in
pharmaceuticals and diagnostics, boasts
broad skills and products in oncology,
immunology, infectious diseases, ophthalmology and neuroscience. Roche says
it is the world leader in in-vitro diagnostics and tissue-based cancer diagnostics,
and its personalized healthcare strategy
aims at providing medicines and diagnostics “that enable tangible improvements in the health, quality of life and
survival of patients.” In 2014, the Roche
Group employed 88,500 people worldwide, invested 8.9 billion Swiss francs
in R&D and posted sales of 47.5 billion
Swiss francs. Genentech, in the United
States, is a wholly owned member of the
Roche Group. Roche is also the majority
shareholder in Chugai Pharmaceutical in
Japan. n
DIAGNOSTICS
MULTIGENE
other than BRCA1 or BRCA2.
For more than half of these patients, the
genetic test would suggest a change in care
over and above any recommendations based on
the patient’s personal and family history alone.
“Our study is distinguished from previously published work by the size of our cohort
together with the availability of detailed personal and family history data collected directly from involved participants,” the JAMA
Oncology study authors stated. “In addition,
our study avoids biases inherent in studies
conducted exclusively on samples available
to genetic testing laboratories because our
participants were all enrolled directly at the
site of referral under uniform criteria.”
Lead author Dr. Leif W. Ellisen of
Massachusetts General Hospital Cancer Center and coauthors wanted to determine how
often multigene panel testing would identify
mutations that warranted some clinical action among women appropriately tested but
lacking BRCA1 and BRCA2 mutations.
Ellisen tells DDNews, “We found that for
women with a personal and/or family history of breast cancer, if you calculate that
woman’s risk of future breast cancer (without
a genetic test), finding a mutation through
multigene testing often leads to a substantially increased calculation of her risk.”
“As a result, you might, for example, not
offer breast MRI screening to that woman
without knowing the test result, but you
would offer it once you had the additional
genetic information,” Ellisen notes. “For
some women, finding a risk gene mutation
could lead to a recommendation for prophylactic breast surgery, and that would not be
a standard recommendation in the absence
of the genetic information.”
“For other women, finding a mutation
might mean they are at risk for a cancer they
did not suspect,” Ellisen said. “For example,
several women with a personal and/or family
history of ovarian cancer were found to have
a mutation that causes risk of ovarian cancer
but also a high risk of colon cancer. These
women would immediately be recommended
to start frequent colonoscopy screening and
in some cases to consider preventive colon
surgery—recommendations that would not
be considered without the genetic mutation.”
While the clinical implementation of
genetic testing for BRCA1/2 preceded
the development of firm mutation-based
management guidelines, “the wide availability
of a validated platform for this testing
contributed to our understanding of genetic
cancer risk and ultimately to more effective
management of these patients,” he says.
The impetus for the study was to ask an
unresolved question regarding genetic testing, which Ellisen puts as: “If we do a multigene test as opposed to simply a test for
BRCA1/2, does finding a mutation in one
of the other genes actually change how we
think about that woman’s risk—and what
measures we would recommend for screening and prevention?”
“In other words, we know that screening
and preventive action need to be based on our
best assessment of risk for that patient, and
the question was whether finding a mutation through multigene testing is likely to
change the risk assessment and consequently
the recommendations,” he continues. “We
found that in the majority of cases, finding
these mutations did change what we would
recommend.”
CREDIT: CHENSIYUAN
Harvard Medical School was one of the institutions involved in a study of multigene testing in
which it was found that women negative for BRCA1 and BRCA2 were shown to harbor other
harmful genetic mutations, most commonly moderate-risk breast and ovarian cancer genes and
Lynch syndrome genes, which increase ovarian cancer risk. Pictured here is the Harvard Yard
area of Harvard University.
Prophylactic mastectomy is “well established to dramatically decrease breast cancer
incidence (risk) in high-risk woman,” Ellisen
points out. “However, making a decision for
such a surgery should be based on the best
risk information possible, and most believe
that such surgery is not indicated in those
who have average or only moderately elevated risk.”
For the study, the authors enrolled 1,046
women and carried out multigene panel testing on all the participants. Among the 1,046
women, 3.8 percent of them (40 women)
who were negative for BRCA1 and BRCA2
had harmful mutations in other moderaterisk genes.
The authors included an additional 23
patients in the study’s clinical management
analysis and results indicate that among 63
women positive for mutations, the majority
of them (33 women, or 52 percent) would
be considered for additional disease-specific
screening and/or prevention measures
beyond those based on personal and family
history alone. Additional family testing also
would be considered for first-degree relatives, according to the results. In the large
majority of mutation-positive cases—58 of
63, or 92 percent—personal and/or family
histories included cancer associated with the
mutant genes.
“Multigene panel testing for patients with
suspected HBOC risk identifies substantially more individuals with relevant cancer
risk gene mutations than does BRCA1/2
testing alone,” the study authors wrote.
“Identifying such mutations is likely to
change management for the majority of
these individuals and their families in the
near term, and in the long term should lead
to development of effective management
guidelines and improved outcomes for atrisk individuals.”
Not everyone in the medical field agrees.
In the JAMA Oncology “Invited Commentary,” entitled, “Usefulness of Multigene Testing—Catching the Train That’s Left the Station,” Dr. Elizabeth M. Swisher of the University of Washington Medical Center in Seattle
wrote: “Multigene testing is rapidly becoming the norm for genetic cancer risk assessment. We must continue to assess the effect
of such testing on clinical care and patient
experience and work to provide meaning-
ful guidelines for cancer-preventive care for
those with less common genetic findings.”
A major argument against multigene testing has been the “need to avoid harm by
providing mutation information on genes
for which guidelines about care management
are not well defined,” she said. “However, in
many high-risk families, we already are harming patients by having inadequate knowledge
about who is at risk.”
“An example is two sisters with ovarian
cancer who tested negative for BRCA1/2
mutations,” Swisher said. “With this information, most physicians would offer age-appropriate risk-reducing salpingo-oophorectomy
to first-degree female relatives, half of whom
are really not at risk.”
A more comprehensive genetic assessment
may identify the cause of the ovarian cancer in
the affected women ( i.e, RAD51C mutation),
Swisher said. By identifying the cause of ovarian cancer in the family, at-risk relatives can be
tested, eliminating unnecessary interventions
in women without the familial risk.
“In this case, non-testing is more harmful
than multigene testing,” she said.
Others have been critical about the cost
of genetics tests because these kinds of lifesaving tests are not readily available to the
poor.
Dr. Robert Nussbaum, Invitae’s chief medical officer, tells DDNews that his company has
tried to make genetic testing more affordable
for the common woman.
“Invitae now offers a patient-pay price that
really brings the price of a test, that used to
be in the $3,000 to $4,000 range a few years
ago, down to $475,” Nussbaum said. “And,
of course, we have institutional and thirdparty payer prices that are still far below what
they had been in the past few years. We know
price has been one of the biggest barriers
to getting valuable genetic testing into the
hands of physicians and patients, and Invitae
is committed to making testing as affordable
and accessible as possible.” n
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CONTRACT SERVICES
BRIEFS
PharmaVoice honors
Advanced Clinical CEO
DEERFIELD, Ill.—Advanced Clinical’s CEO, Leo Sheri-
dan, was recently recognized in the 2015 PharmaVoice Top 100 Most Inspiring People list for his
innovation and leadership skills in the life-sciences
industry. Advanced Clinical is a global clinical organization that offers full-service contract research
organization, staffing and functional service provider solutions, including patient recruitment and
retention services. Sheridan established Advanced
Clinical in 1994, and is the founder, CEO and president of The Advanced Group of Companies, which
consists of Advanced Clinical, Advanced Resources,
the WunderLand Group and TriWorth.
ACRO holds second annual
Innovation Month
WASHINGTON, D.C.—The Association of Clinical
Research Organizations (ACRO) recently held its
second annual CRO Innovation Month with the
theme of “Transforming Patient Centered Drug
Development.” The organization released a trio
of videos on CROs and how they are educating
and engaging patients and integrating their suggestions into the clinical research process,
including “Collaboration,” “Clinical Trials—A
Patient’s Perspective” and “Patient-Centered
Drug Development: Educate.”
Doug Peddicord, ACRO’s executive director, remarked: “Stay tuned throughout the fall,
as ACRO will be releasing a number of videos
focused on topics such as: the importance of realworld data for sponsors, regulators and payers;
promoting diversity in clinical trials; the patient’s
perspective on clinical trial participation; and
CRO efforts to collaborate to improve the drug
development process. Policymakers and regulators globally are weighing in on these topics
and CROs, with the pivotal role they play in the
drug development process, are well positioned to
inform and influence these discussions.”
IN THIS SECTION
Asthma/Allergy/Autoimmune
No seven-year itch for CRO..................... 38
Awards and honors
PharmaVoice honors
Advanced Clinical CEO............................ 38
Clinical research
goBalto is making tracks ........................ 38
News roundup
Contractual matters................................. 40
Patient-centered drug
development
ACRO holds second annual
Innovation Month.................................... 38
Regulatory functions
Navitas introduces new regulatory
process outsourcing model..................... 38
No seven-year itch for CRO
At over $158 million, Rho nets its
largest federal contract ever
BY LORI LESKO
CHAPEL HILL, N.C.—Contract research organization Rho has been
awarded a $158.3-million, seven-year cooperative agreement—the
largest federal contract in its 31-year history—slated to provide statistical and clinical coordinating services to the Division of Allergy,
Immunology and Transplantation (DAIT) of the National Institute
of Allergy and Infectious Diseases (NIAID) at the U.S. National Institutes of Health.
The North Carolina-based CRO, which provides clinical research
services for commercial and federal markets, will provide these
services for DAIT’s large clinical research consortia in, predictably,
the areas of asthma and allergic diseases, autoimmune diseases and
transplantation.
“Rho is excited to be selected as DAIT’s Statistical and Clinical
Coordinating Center to support the important work they are doing
to help combat serious health concerns, such as asthma and allergies,
autoimmune diseases and transplantation,” said Russ Helms, CEO
of Rho. “Rho’s expertise and resources will help assure top-notch
operational support, statistical analysis, clinical data management
and bioinformatics services.”
Rho will use this money “in-house to support 89 clinical research
studies in immune tolerance, asthma, atopic dermatitis, autoimmune
diseases and organ transplantation,” according to Karen Kesler, senior
statistical scientist and Leadership Group principle investigator (PI).
The National Institutes of Health, through the National Institute of
Allergy and Infectious Diseases, is awarding a $158.3-million, sevenyear cooperative agreement to Rho.
All of the money supports work for these studies, including designing them, coordinating the research, gathering the data, ensuring
the safety of the subjects and analyzing the results, she notes, adding, “Since this award is a continuation of ongoing research already
being conducted by Rho, we are tasked with finishing many of the
current studies as well as starting up more than 50 new studies. These
studies will help researchers gain a better understanding of human
RHO CONTINUED ON PAGE 40
Navitas introduces
goBalto is
new regulatory process making
outsourcing model
tracks
Move is driven in large
part by pressure on
pharmas and biotechs to
do more regulatory work
even as budgets tighten
More than 2,000 CROs
and pharmas now
employ company’s
Activate application
BY KELSEY KAUSTINEN
SAN FRANCISCO— goBalto Inc., a
BY LLOYD DUNLAP
companies. To address the new regulatory
landscape, Navitas has integrated industry insights from its nets in the regulatory
domain and its technology capabilities and
partnerships, into an innovative suite of process outsourcing services for life-sciences
companies under the banner “Process Out-
leading provider of cloud-based clinical study startup solutions, announced
this summer that it is now serving
three of the top five contract research
organizations (CROs), with more than
2,000 CRO and pharmaceutical users
in more than 60 countries worldwide
using goBalto’s Activate to manage,
track and complete study startup tasks.
In addition, the company also serves
more than two-thirds of the top 20
pharmas, managing clinical trial documents for them globally, and represents more than 70 percent of clinical
trial sites in Phase 2 and Phase 3 work
for the top 25 pharma companies.
NAVITAS CONTINUED ON PAGE 40
GOBALTO CONTINUED ON PAGE 39
PRINCETON, N.J.—The workload for regula-
tory functions of pharmaceutical companies
has continued to increase in recent years,
driven by greater and more complex global
regulatory requirements. At the same time,
there are increasing cost pressures on regulatory functions. Companies are being forced
to adopt innovative technology solutions and
outsourcing models as potential ways to meet
these cost, capability and capacity challenges.
Shalabh Kumar, global head of services at
Navitas, explains that the growing requirement to do more with less has forced companies into outsourcing, with larger pharmas
leading the parade.
Regulatory process outsourcing in particular is an emerging solution for global
Pharmas and biotechs have ever-growing
regulatory process concerns—from the FDA
(pictured here) and other agencies globally,
and they need to make money go farther than
before, leading to more reliance on services
provided by companies like Navitas.
CONTRACT SERVICES
GOBALTO
“There is intense pressure to
speed clinical trials and restrain
costs, but inefficiencies tied to
complicated protocols, globalization and paper-based methods have
stalled these efforts,” said Sujay
Jadhav, goBalto’s CEO. “The current
status of clinical trials has encouraged industry leaders to embrace
cloud-based solutions. Our study
startup methodology aligns with
the goal of faster development by
significantly impacting cycle times,
leading to greater cost savings
and faster market entry, making
valuable therapies available to
patients sooner.”
Activate is a purpose-built
software-as-a-service application
hosted in the cloud, and helps
sponsors, CROs and trial sites
get studies launched as quickly
as possible.
goBalto touts a variety of ways
in which its Activate service can
support CROs, including data
sharing, improving quality and
reducing cycle time by 66 percent.
The company asserts on its website that the Activate platform can
help lower the average cycle time
for CROs to complete registration
documents from an average of 35
days to just 14. Activate also allows
organizations to automate workflows to alert for and track when
submissions are due, and offers
workflow templates to help define
the regulatory documents and
submissions required for more than
60 countries.
So far this year, goBalto has
released two new versions of Activate, with the first released March
23. That version was tailored to
include submissions and other key
activities and milestones that aren’t
effectively managed under existing
clinical systems, with new features
that include expired document
management, alerts that point out
opportunities to improve cycle
times and an API enhancement to
support seamless integration with
investigator portals, among others.
The second update was announced
July 7, with new features such as
automatic/intelligent distribution
of study documents and enhanced
single sign-on enabling streamlined
integration with adjoining customer systems, to name a few.
“Many of the steps involved in
study startup create delays, but
with the deployment of goBalto
Activate, a proven, purpose-build
cloud-based study startup solution,
we can make a disruptive impact.
Our partnership is critical to our
goal of achieving automation in
our clinical trials processes and
our mission of cutting costs by
shortening timeframes for developing therapies needed by patients
worldwide,” Ross Pettit, senior vice
president of clinical development
operations at Infinity Pharmaceuticals, said in a news release.
In September, a two-year part-
nership was announced between
goBalto and the Society for Clinical Research Sites (SCRS), a global
trade organization representing
clinical research sites. Per the
agreement, goBalto will participate
as a Global Impact Partner (GIP), a
position meant to support critical
dialogue between clinical research
sites and industry stakeholders.
The company will also participate
on the SCRS Global Impact Board
at an executive level to develop and
execute strategic initiatives for the
organization.
“goBalto represents a handful
of technology solution companies
that have openly endorsed their
commitment to clinical research
sites,” Christine Pierre, president
of SCRS, remarked of the partnership. “SCRS’ GIPs are focused on
acknowledging the realities that
today’s sites face, and actively
addressing their challenges. goBalto is bringing technology disruptions to the cumbersome and inefficient clinical trial process, and we
are proud to welcome them as our
newest Global Impact Partner.”
Jae Chung, goBalto’s president and founder, added, “As a
company dedicated to delivering
innovative technologies that guide
work and help standardize global
processes by mitigating clinical risk and operational cycle
times via ‘smart’ workfl ows, we
recognize the critical role clinical
research sites play as collaborators
in fulfilling this mission.” n
Jae Chung, founder and president
of goBalto, at this year’s DPharm
conference, with one of the goBalto
mascots. The company is named
after a famous sled dog.
Cambridge Healthtech Institute’s 15th Annual
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CONTRACT SERVICES
CONTRACTUAL MATTERS
An overview of recent
news on the CRO
and CMO fronts
T
BY JEFFREY BOULEY
HE CONTRACT RESEARCH and contract
manufacturing organizations—and the
companies that serve them—often work
in the background so effectively that we
never see them, so let’s bring a few into the limelight and see what they’re up to.
INC Research launches
site advocacy group
RALEIGH, N.C.— This summer, INC Research
Holdings Inc., a global Phase 1 to 4 contract research organization, announced the launch of what
it says is the industry’s first site advocacy group
(SAG) devoted to the scientific and operational
aspects of clinical research. The SAG initially will
focus on central nervous system (CNS) protocols—
recognized as among the more complex therapeutic
areas in clinical research—targeting psychiatry studies that will include, but are not limited to, those
in schizophrenia, attention-deficit/hyperactivity
disorder, depression and bipolar disorder.
“Through this forum, INC Research will collaborate with clinical research sites that have direct
experience in psychiatry studies to gain their
insights into the most common challenges and
operational efficiencies that can be implemented
for future studies,” said Clare Grace, vice president of site and patient access. “We will leverage these expert insights to incorporate the site
and patient voice in the evaluation of psychiatry
study protocols for scientific merit and operational
success. Ultimately, we expect our Site Advocacy
Group to embed efficiencies in the planning phase
and increase the quality and speed of these clinical
trials for our customers.”
A recent study by the Tufts Center for the Study
of Drug Development found that drugs to treat CNS
diseases such as epilepsy, Alzheimer’s, autism,
schizophrenia and depression take 35 percent longer to develop than other drugs.
“Creating this SAG underscores INC Research’s
commitment to better leveraging the expertise of
clinical research sites worldwide in developing
treatments for important health conditions,” said
Dr. Michael Gibertini, president of clinical development. “Engaging with sites early on and in a mean-
RHO
immunology, immunologic diseases and new
immune-based therapies.”
Five Rho employees are serving as PIs on
this project: Kesler, as noted above; Dr. Ronald
W. Helms, chairman and overall PI; Dr. Samuel
Arbes, senior research scientist and group leader for the Asthma and Allergic Diseases Group;
Dr. David Ikle, senior statistical scientist and
group leader for the Transplantation Group;
and Dr. Lynette Keyes-Elstein, senior statistical
scientist and group leader for the Autoimmune
Diseases Group. Additionally, day-to-day management will be provided by Michelle Walter,
senior project director.
The project combines services that were
previously under six separate awards from
DAIT, five of which were held by Rho. This
project has been funded with federal monies
from NIAID under Grant No. UM2-AI117870.
In other NIAID news, the institute is
ingful way is critical to enhancing protocol design
and study conduct.”
PharmaCyte Biotech’s CRO
voted Australia’s favorite for 2015
SILVER SPRING, Md.—Early summer saw PharmaCyte
Biotech Inc., a clinical-stage biotechnology company focused on developing targeted treatments
for cancer and diabetes using its signature live-cell
encapsulation technology, Cell-in-a-Box, announce
on behalf of contract research organization (CRO)
Clinical Network Services (CNS) that the latter had
been voted Australia’s favorite contract research
organization for 2015.
CNS was chosen by PharmaCyte Biotech as
its CRO to prepare for and conduct PharmaCyte’s
upcoming Phase 2b clinical trial in pancreatic cancer.
The award was presented to CNS at the 2015
ARCS Scientific Congress. ARCS Australia Ltd., previously known as the Association of Regulatory and
Clinical Scientists, is a professional development
organization for those working in the development
of disease therapies.
“As a company, CNS has always been committed
to maintaining a positive culture focused on how we
interact with each other, our clients and importantly
the wonderful clinicians, coordinators and pharmacists who are at the forefront of delivering our trials
to patients,” said Gabrielle McKee, chief operating
officer of CNS.
PharmaCyte CEO Kenneth L. Waggoner offered
his company’s congratulations, stating, “When we
were evaluating CROs that might best assist us in
our Phase 2b clinical trial in those with advanced
pancreatic cancer in Australia, it became evident
early on in that process that CNS was one of
Australia’s leading CROs.”
Quotient Clinical expands
its data sciences capabilities
NOTTINGHAM, U.K.—Quotient Clinical, which touts
itself as “the Translational Pharmaceutics company,” has expanded its data sciences services in
response to increasing customer demand, doubling
the footprint of its facilities in Edinburgh and Nottingham, as well as increasing its specialist headcount and appointing a new vice president. Quotient
notes that data sciences are an integral part of its
services, delivering real-time data to customers for
review and interpretation, enabling crucial dosing
decisions to be made during the course of a study.
Greg Johnson, the new vice president of data sci-
launching a new study to better understand
how adults develop respiratory syncytial
virus (RSV), a virus that causes cold-like
symptoms, in order to assist researchers in
developing and testing future antivirals and
vaccines to combat the virus.
RSV is the most common cause of lower
respiratory tract infections—including pneumonia and bronchiolitis—among young
children worldwide, according to the U.S.
Centers for Disease Control and Prevention.
In the United States each year, RSV leads to
an average of about 55,000 hospitalizations
among children younger than 5 years, with
most of these hospitalizations involving
infants younger than 6 months. Healthy
adults infected with RSV tend to develop
cold-like symptoms and recover without
any problems, but the infection can cause
severe disease in premature infants, children
younger than two years with heart or lung
problems, children and adults with weakened
immune systems and the elderly. RSV infec-
NAVITAS
tion causes roughly 14,000 deaths annually
among U.S. adults older than 65 years.
“Challenge studies such as this are a
unique way of enabling scientists to monitor, in a controlled setting, the natural history of a disease in exquisite detail, using the
most powerful tools of molecular biology,”
said NIAID Director Dr. Anthony S. Fauci.
“By studying RSV infection in healthy adults,
we hope to improve understanding of how
this infection develops and determine the
suitability of this particular strain of the virus
for use in future RSV vaccine and treatment
trials.”
Investigators will use a laboratory-developed strain of RSV called RSV A2, which is
commonly used in research. The strain is
the first molecularly cloned challenge virus,
meaning the RSV A2 study virus originates
from a single clone of the virus strain and has
been tested to ensure it is not contaminated
with other infection-causing pathogens. n
sourcing Enhanced by Technology.”
The suite of Navitas regulatory services
includes submissions and report publishing,
license maintenance for marketed products,
labeling and artwork services, regulatory
information management and regulatory
strategy and support. Navitas also provides
subject matter expertise in evolving electronic submissions standards and health
authority-specific guidelines and processes.
At the core of these services is the company’s
state-of-the-art Global Delivery Center in
Chennai, India, and an emerging delivery
center in Bogota, Columbia, providing scale
and cost efficiency.
As an innovator in the regulatory process
outsourcing industry, Navitas recently celebrated three years of a global regulatory
submissions partnership with one of the
world’s largest pharmaceutical companies.
The partnership program compiles,
formats, publishes and distributes regulatory compliant submissions to drug approval agencies throughout the world. Navitas
functions as an extension of the company’s
internal Regulatory Operations group and
handles more than a third of the company’s
annual submissions.
“Publishing is our most mature and bestestablished function,” Kumar states. “Labeling is also very important where we have a
long industry record, as well as safety monitoring,” which, he notes, “never goes away.”
Navitas also provides the proprietary software PharmaReady, a web-based electronic
document management and e-submission
software with ease of installation, ease of
use, regulatory compliance and affordability as its primary features, typically used by
Naviras’ smaller clients (the company uses
larger clients’ own software in many cases).
PharmaReady is specifically designed for
both emerging and large life-science organizations where ease of installation, ease of
use, regulatory compliance and affordability
are the primary business drivers. The PharmaReady solution suite is designed for management of standard operating procedures,
work instructions, training records, eCTD
submission documents and all other electronic documents, and is in full compliance
with global regulatory requirements.
Kumar adds that “The challenges faced by
our clients in the pharmaceutical industry in
light of increasing and more complex regulatory requirements can only be addressed by
innovative solutions. In integrating our process outsourcing and technology capabilities,
we have created a suite of services which are
unique in this sector.”
The Navitas team has been assembled,
bringing together the proven expert teams of
TAKE Life Sciences and WCI Consulting and,
adding to this core, a range of experts from
the worlds of clinical development, regulatory, technology and consulting.
“We have built the Navitas team specifically to deliver insight to our clients, to develop
pragmatic solutions together and to support
their deployment and operation. We deliver
advice, solutions and outsourcing services in
clinical, regulatory, safety and content management,” Kumar summarizes.
“We are proud that our legacy businesses
have served the sector for some 15 years and
have allowed us to work with 100 of the top
life-science companies. Our team has now
grown to over 500 staff.” n
ences, has more than 25 years of industry experience in directing biometrics and data sciences at
large contract research organizations.
“Greg brings a wealth of industry experience
that will be invaluable as we grow our data sciences offering,” noted Mark Egerton, CEO of Quotient Clinical. “Demand for these services is rapidly
increasing, and we are now undertaking electronic
data capture, data management, pharmacokinetics,
modeling and simulation, biostatistics and reporting
on over 80 percent of our customer programs, compared to just 50 percent a few years ago.”
“Translational Pharmaceutics can have a profound impact on reducing development timelines
and associated costs, and this is driving an increase
in demand for all our services,” Johnson said.
ViiV and Desano manufacturing deal will
allow competitive supply of dolutegravir
LONDON—ViiV Healthcare and Desano Pharmaceuticals announced this summer a strategic manufacturing agreement to enable production in China of
dolutegravir. The agreement will offer an additional
source of the dolutegravir active pharmaceutical
ingredient (API) and allow ViiV Healthcare to offer
a competitive supply of the finished product (dolutegravir 50mg, marketed under the name Tivicay) for
China and a number of developing countries, subject to national approvals. This strengthens ViiV
Healthcare’s commitment to improve access to its
treatments for people living with HIV, especially in
countries hardest hit by the disease.
“This manufacturing agreement with Desano
for dolutegravir is a significant achievement to
facilitate access to our medicines. With our recent
agreement with the Medicines Patent Pool and
our other access initiatives, this deal is aligned
with our ongoing commitment to improve access
to our medicines in countries where the need is
greatest,” said Dr. Dominique Limet, CEO of ViiV
Healthcare, adding that Shanghai-based Desano
is a high-quality manufacturer that is well suited
to partner with ViiV.
Under the agreement, Desano will manufacture
the API of dolutegravir to feed in to the GlaxoSmithKline/ViiV Healthcare supply chain for onward sale
in China and developing countries covered by the
agreement. ViiV Healthcare and Desano are also
exploring further options for future manufacture of
finished drug product and fixed dose combinations
of dolutegravir with APIs. n
BUSINESS &
GOVERNMENT POLICY
Amgen’s Repatha secures
FDA approval
THOUSAND OAKS, Calif.—Amgen recently received
U.S. approval for Repatha Injection, a human
monoclonal antibody that inhibits proprotein
convertase subtilisin/kexin type 9, a protein that
hampers the liver’s ability to clear low-density
lipoprotein cholesterol (LDL-C), or “bad” cholesterol, from the blood. Repatha is indicated as an
adjunct to diet and maximally tolerated statin
therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who
need additional help lowering LDL-C, and as an
adjunct to diet and other therapies for patients
with homozygous familial hypercholesterolemia
who require additional lowering of LDL-C.
“Data from key clinical studies have shown
that Repatha significantly reduces LDL cholesterol
in patients who have not been able to lower their
LDL cholesterol through diet and statins alone,”
said Dr. Sean E. Harper, executive vice president
of research and development at Amgen.
Afatinib applications
accepted by FDA, EMA
RIDGEFIELD, Conn.—The U.S. Food and Drug Admin-
istration (FDA) and the European Medicines Agency
have accepted filing applications for Boehringer
Ingelheim’s afatinib for the treatment of patients
with advanced squamous cell carcinoma (SCC) of
the lung progressing after first-line chemotherapy
treatment. The FDA has also granted afatinib
orphan drug designation. These submissions are
based on results of the Phase 3 LUX-Lung 8 trial,
which compared afatinib with Tarceva (erlotinib) in
patients with advanced SCC of the lung progressing
after treatment with first-line platinum-based chemotherapy. Afatinib use met the primary endpoint
of progression-free survival, reducing risk of cancer
progression by 19 percent, and the secondary endpoint of overall survival, reducing the risk of death
by 19 percent compared to erlotinib. Quality-of-life
improvement and control of cancer symptoms was
also observed in afatinib versus erlotinib.
IN THIS SECTION
M&A activity
The XF factor (SEAHORSE from cover).... 43
Toward a total solution........................... 41
Regulatory activity
Afatinib applications
accepted by FDA, EMA............................ 41
Amgen’s Repatha
secures FDA approval.............................. 41
For your approval..................................... 41
Sexual dysfunction
A partner for the global stage................. 41
Tools and technology
On the cutting edge................................. 42
Toward a total solution
FOR YOUR
APPROVAL
Roche acquires Kapa
Biosystems to boost
next-gen sequencing
product offerings
A collection of recent
regulatory approvals
and actions globally
BY ILENE SCHNEIDER
BASEL, Switzerland—Biotech and pharma
giant Roche has signed an agreement to
acquire Kapa Biosystems Inc., a privately
held company headquartered in Wilmington, Mass., as part of an effort to expand its
next-generation sequencing product line.
Financial terms of the transaction were not
disclosed.
Kapa Biosystems, a provider of genomic
tools in the life-sciences sector, uses proprietary technologies to optimize enzymes for
next-generation sequencing (NGS), as well
as polymerase chain reaction (PCR) and realtime PCR applications. Kapa’s proprietary
protein engineering technology is reportedly highly customizable and allows for the
The acquisition deal with Kapa Biosystems
follows on the heels of a deal early this year to
acquire Signature Diagnostics, which also had
heavy next-generation sequencing overtones.
Pictured here is a Roche researcher testing the
pharmacokinetics of a drug candidate.
generation and screening of large numbers
of enzyme variants. Tailored enzymes with
improved performance for specific applicaTOTAL CONTINUED ON PAGE 45
A PARTNER FOR
THE GLOBAL STAGE
Apricus sends out the call
for global development
partner for Femprox
BY KELSEY KAUSTINEN
SAN DIEGO— In hopes of advancing
Femprox, a topical alprostadil cream for the
treatment of female sexual interest/arousal
disorder (FSIAD), Apricus Biosciences Inc.
has announced its intention to secure a global development partner. Apricus, a biopharmaceutical company developing innovative
medicines in the fields of urology and
rheumatology, has completed nine clinical
studies for the drug to date, including a proofof-concept trial consisting of nearly 400
subjects that achieved statistical significance
in both its primary and secondary endpoints.
The company is now looking to take Femprox
to the global market.
“Given the recent FDA approval of Sprout
Pharmaceuticals Inc.’s flibanserin for female
sexual dysfunction, Apricus now believes
that a potential regulatory path exists in the
U.S. for Femprox,” Richard Pascoe, CEO of
Apricus, commented in a press release. “We
will immediately initiate a disciplined partnering process to identify potential licensees
for the global development and commercial-
F
BY JEFFREY BOULEY
CREDIT: ROCHE
BRIEFS
In addition to Femprox, Apricus has potential
products in the pipeline for hypogonadism,
Raynaud’s disease and various urological
conditions. On the commercial side, its lead
product is Vitaros, an erectile dysfunction
treatment pictured here.
ization rights for Femprox with the goal of
maximizing our return on investment for the
potential benefit of shareholders.”
Femprox is a 0.4 percent alprostadil cream
meant to treat FSIAD. The drug releases a
local, relaxant effect on vulvar and clitoral
blood vessels, which leads to increased blood
flow that is in turn expected to increase lubrication and sensory feedback to boost sexual
arousal in women. Femprox is delivered using
Dodecyl 2-(N, N dimethylamino)-propionate,
Apricus’ drug delivery technology. This
technology is described as “a novel propriePARTNER CONTINUED ON PAGE 44
ROM ORPHAN DRUG
designation for a gene
therapy that treats
mucopolysaccharidosis
type I to approval of a
hemophilia treatment,
we have a number of
quick items to present to you and give
you an idea of the breadth and depth
of recent regulatory activity in Europe
and the United States.
RGX-111 gene therapy
gets orphan drug status
ROCKVILLE, Md.—Early October saw REGENX-
BIO Inc., a biotechnology company involved
in gene therapy, announce that the U.S. Food
and Drug Administration (FDA) had granted
its Orphan Drug Designation to the company’s
investigational gene therapy product candidate RGX-111 for the treatment of mucopolysaccharidosis type I (MPS I).
“REGENXBIO is pleased to have received
Orphan Drug Designation from the FDA for
RGX-111,” said Kenneth T. Mills, president
and CEO of REGENXBIO. “MPS I is a severely
debilitating disease, and patients and their
caregivers do not currently have adequate
therapeutic options. We remain committed
to our vision of developing gene therapies
for patients with high unmet medical needs,
including MPS I.”
MPS I is a rare neurodegenerative disease
caused by deficiency of the a-l-iduronidase
(IDUA) gene, and somewhere around 1,000
individuals with MPS I are estimated to be
born each year worldwide. Symptoms include
excessive accumulation of fluid in the brain,
spinal cord compression and cognitive impairment. RGX-111 uses an AAV9 vector to deliver
the IDUA gene to the central nervous system.
REGENXBIO intends to file an
Investigational New Drug Application (IND)
with the FDA in the first half of 2016 to
support the initiation of a dose-escalation
Phase 1/2 clinical trial of RGX-111 beginning
in the first half of 2016.
Zalviso gains marketing
authorization in EU
REDWOOD CITY, Calif.—AcelRx Pharmaceuticals
Inc. has announced that the European Commission (EC) approved Zalviso (15 micrograms
APPROVAL CONTINUED ON PAGE 44
ON THE CUTTING EDGE
A roundup of instrumentation,
software and other tools and
technology news
BY JEFFREY BOULEY
TOOLS &
TECHNOLOGY
A SCIENTIFIC PRODUCT SUPPLIER
expands and a laboratory instruments, software, services and consumables provider collaborates with
a medical school. A companion diagnostic gets shown around a medical oncology conference and a life-sciences tool company for drug discovery announces an important new customer. That and
more in this month’s roundup of the tech that keeps
drug discovery and development moving forward.
Herolab recently added the Hi Cen
GR high-end-performance,
refrigerated centrifuge to its range of
centrifuges and accessories.
PCR workstations, UV radiation systems
for crosslinking or tissue culture studies,
transilluminators, germicidal lamps and
UV hand lamps/analysis lamps.
Herolab also recently launched the Hi
Cen GR to add to its range of centrifuges
and accessories.
This large-volume floor-standing refrigerated centrifuge has a maximum capacity of 4 x 1000ml and can be used with
swing-out or angle rotors. Its speed of up
to 18,000 rpm and g-force of 36.223 x g
puts this model at the high end of performance levels.
Herolab opens new U.K. base
Agilent collaborates
with Weill Cornell to advance
research in ALS
WIESLOCH, Germany— Herolab GmbH
SANTA CLARA, Calif.—Agilent Technologies
Laborgeräte, which manufactures products for life-sciences research, diagnostics
and production, has opened a U.K.-based
office. This new office in Cambridge has
been opened to help service the growing
number of users in the United Kingdom
and well as offering sales and support
for a number of International dealers and
customers.
This expansion coincides with the
company recently being awarded the
German Stifterverband seal, which is
only given to those companies who can
show new discoveries and who can create
innovative solutions.
Herolab produces products for a number of sectors in the scientific market.
The company’s centrifuge division, for
example, offers high-speed models from
universal benchtop centrifuges, underbench models, floor-standing centrifuges
on rollers and extra-large centrifuges up
to 6 x 1000 ml volume. A wide choice of
Herolab-manufactured centrifuge tubes
and bottles using different high-quality
plastics is available for all centrifuges in
the range and other brands. Additionally,
Herolab can produce plastic labware for
specific customer requests. The company’s
gel documentation division has a number
of different models for chemiluminescence and fluorescence applications for
the imaging of gels and blots. The Herolab UV products division range includes
Inc. recently announced it is collaborating
with Dr. Steven Gross, a faculty member in
the Department of Pharmacology at Weill
Cornell Medical College in New York City,
to advance research in amyotrophic lateral sclerosis (ALS), also known as Lou
Gehrig’s disease. Agilent will provide the
latest mass spectrometry technology to
support his research, working toward an
understanding of how the most common
form of this disease develops in the body.
The Agilent 6230B LC TOF and 6550A
LC Q-TOF mass spectrometers will be
housed in the Gross’ laboratory—his
expertise is in pharmacology and cell
biology, particularly in relation to the role
of nitric oxide as a signaling molecule.
Gross, along with Dr. Qiuying Chen, an
assistant research professor of pharmacology at Weill Cornell, and Ben Schwartz,
a student in the pharmacology doctoral
program at Weill Cornell Graduate School
of Medical Sciences, is studying the most
common form of ALS, sporadic amyotrophic lateral sclerosis, which accounts
for about 90 percent of all ALS cases and
has no obvious genetic driver.
“Translational research using a
combination of biological disciplines—
genomics, proteomics, transcriptomics,
metabolomics—is an emerging trend in
academia,” said Steven Fischer, market
director for life-science research in academia and government at Agilent. “Most
researchers, however, do not know how to
perform multi-omic analysis, and successful examples are needed. Agilent is working with the Gross lab at Weill Cornell to
advance the multi-omics-based approach
to disease research, using sporadic ALS to
demonstrate the power of this method.”
“Our newly established scientific collaboration offers a rare opportunity to obtain
and integrate multi-omics data, with the
potential to yield an unprecedented
understanding of the molecular basis for
this devastating disease,” Gross noted.
“We anticipate that this scientific work
with Agilent will continue into the future
as we apply multi-omics approaches to
other poorly understood diseases with
unmet clinical needs.”
In September, Myriad Genetics
(research staff of which are pictured
here) presented data related to new
studies on the myChoice HRD and
Tumor BRACAnalysis CDx
companion diagnostic tests and
final results from the EMPATHY-P
clinical utility study on Prolaris.
Myriad presents new data
on its companion diagnostic
and prostate cancer tests
molecular interactions,” announces that
Natick, Mass.-based XTAL BioStructures
Inc., a pharmaceutical and biotechnology
industries service provider, is adding the
BiOptix 404pi to its suite of biophysical
tools.
XTAL BioStructures is a contract
research organization that provides drug
discovery and intellectual property development services to the pharmaceutical
and biotechnology industries, including
high-quality protein production, biophysical characterization and X-ray crystallography with a focus on affinity-based
screening techniques.
“This partnership will further XTAL’s
dedication to providing high-quality research services through the availability of the
BiOptix Enhanced Surface Plasmon Resonance (e-SPR) technology, an advanced
and highly sensitive optical technology,”
said Dr. Robert K. Suto, president and chief
scientific officer of XTAL BioStructures.
XTAL is now able to offer customers
access to BiOptix’s patented e-SPR technology, which delivers high sensitivity
(100 Da) and higher throughput by combining proprietary technology with an
advanced, multi-injector fluidics system.
“With the addition of the BiOptix 404pi
label-free system to their existing suite
of biophysical tools, both companies
can now work together to assist those
customers who need both biophysical
assessment and real-time, label-free
interaction analysis to move their drug
discovery projects forward,” said Rick
Whitcomb, president and CEO of BiOptix.
SALT LAKE CITY—Myriad Genetics Inc. in
September announced three poster presentations being featured at the 40th
European Society for Medical Oncology
(ESMO) meeting in Vienna, Austria. The
presentations include new studies on the
myChoice HRD and Tumor BRACAnalysis
CDx companion diagnostic tests and final
results from the EMPATHY-P clinical utility
study on Prolaris.
“Myriad continues to place a strong
emphasis on molecular diagnostic
research with the goal of enabling personalized medicine and improving patient
outcomes. We are presenting exciting new
data on the unique ability of our companion diagnostics to identify the highest
number of patients who may benefit from
drugs that target the DNA-repair pathway,
such as PARP inhibitors,” said Dr. Jerry
Lanchbury, chief scientific officer of Myriad. “We’re also presenting the final results
for the EMPATHY-P study that show the
Prolaris test provides essential clinical
information to help physicians select men
with prostate cancer who are good candidates for active surveillance versus those
who need more medical treatment based
on a genetic evaluation of their tumor.”
BiOptix announces partnership
with XTAL BioStructures
BOULDER, Colo.—BiOptix, a life-sciences
tools company that provides what it calls
“an affordable and powerful solution for
drug discovery scientists that require
label-free, real-time detection of bio-
Syngene’s G:BOX image analysis
system could help to develop stem
cell therapies for repair of injured
heart tissues, thanks to its
installation in the Lithuanian
University of Health Sciences
Academy of Medicine.
G:BOX Chemi XRQ used
to study mechanisms of
cardiac myocyte function
FREDERICK, Md.—Syngene, a global man-
ufacturer of image analysis solutions,
noted recently that the G:BOX Chemi XRQ
high-resolution, multiapplication image
analysis system is being successfully
used at the Lithuanian University of Health
Sciences Academy of Medicine to study
molecular mechanisms of cardiac stem
cell function that could help in developing
stem cell therapies for heart repair.
Researchers in the Laboratory of Cell
Culture at the university are using the
G:BOX Chemi XRQ system to image and
analyze proteins on chemiluminescent
western blots and DNA gels stained with
SYBR Safe dyes. The image analysis data
is being used to investigate the effects
that genetic modification have on how
stem cells differentiate into cardiac myo-
cytes and integrate into cardiac tissue.
Dr. Ieva Antanaviciute, a research
scientist at the Laboratory of Cell Culture stated: “Our lab is focused on gap
junction-mediated intercellular communication. We study expression of gap junction proteins (connexins) under different
environmental conditions in model cell
lines (HeLa) also skeletal myoblast. To
analyze our results, we need an imager
that can perform well with DNA gels as
well as chemiluminescent western blots.
We reviewed a range of imaging systems
because we wanted to get the best value
for our money. The price and service are
what attracted us to the G:BOX Chemi
XRQ, as the system generated good,
publication-quality images and we have
the opportunity to upgrade with different
filters.”
Oracle gets busy
REDWOOD SHORES, Calif.—Oracle has made
a number of announcements recently
about new customers in the life-sciences
sector. In July, it noted that Japanese
pharma Kowa Co. Ltd. has migrated to
Oracle Argus Cloud Service Global and
Oracle Argus Cloud Japan to help manage
compliance with the increasingly complex
regulatory requirements and reduce its
overall pharmacovigilance IT spending.
Further, on Sept. 29, Oracle noted that
emerging biopharmaceutical organizations face a growing number of regulatory
requirements and, due to increased competition, acute pressure to speed time to
market, following that with an announcement that 93 such emerging biopharma
organizations worldwide have become
new customers in the past year, adopting
Oracle Health Sciences solutions.
Late September saw a more focused
and specific announcement as well, that
LSK Global Pharma Services, a full-service
contract research organization in South
Korea, had adopted cloud-based Oracle
Health Sciences InForm to improve its clinical development processes, streamline
data capture and speed up trial timelines.
Raising the bar with Chemi FP
western blot substrate?
SAN FRANCISCO—Gel Company/Aplegen
recently announced “its most sensitive
HRP substrate for western blotting yet,”
a chemiluminescent product joining more
than 800 other reagents and consumables
for life-sciences researchers.
Chemi FP reportedly has attomole
sensitivity and a very long-lasting signal
output. The light emission is stable for
10 times longer than with typical ECL
substrates. This now enables the user to
detect bands not usually visualized with
other substrates that are commonly used.
Importantly, the high signal-to-noise level
and large dynamic range of the product
makes it ideal for quantifying low-intensity bands, the company maintains, and
the chemilfluorescence emission allows
the Chemi FP to be imaged using chemifluorescence imaging techniques in addition to traditional CCD imaging systems
and film. n
SEAHORSE
oxidation, and metabolism of glucose
and amino acids for kinetic metabolic
information.
Agilent plans to use Seahorse’s proprietary
XF Technology to research the role of cell
metabolism in neurodegeneration, aging, cancer, cardiovascular disease, cell physiology, toxicology and hepatobiology, immunology, infectious diseases, mitochondrial diseases, model
organisms, obesity, diabetes, metabolic disorders, screening and translational medicine.
“Seahorse Bioscience’s unique technology is the perfect complement to Agilent’s
market-leading separations and mass spectrometry solutions, in particular for metabolomics research and disease research in
pharma,” according to Patrick Kaltenbach,
president of Agilent’s Life Sciences and
Applied Markets Group. “The combination
of these two platforms gives scientists a more
comprehensive and faster path to researching the most challenging diseases affecting
mankind.”
“Seahorse’s team and technology are an
ideal fit for Agilent and for our customers,
and we look forward to bringing them on
board,” Kaltenbach adds.
Michele Drake, corporate media relations
manager for Agilent, tells DDNews that “The
acquisition of Seahorse Bioscience is one of
Agilent’s largest and important to the company, but we have made two larger, previous
acquisitions that were critical to the evolution of Agilent as a company focused on life
sciences, diagnostics and the applied chemicals market. Those two acquisitions are Varian in May 2010 for $1.5 billion and Dako in
June 2012 for $2.2 billion.”
Agilent is continuously monitoring the
market for opportunities to complement
its portfolio, Kaltenbach said. The Seahorse
technology “complements Agilent’s strengths
in metabolomics and therefore enables us to
serve our customers in research and pharma
even better in the future.”
Drake notes that “Once the acquisition
is completed, Seahorse will become part
of Agilent. The majority of Seahorse’s staff
is expected to join Agilent. There are no
imminent plans to move any of the Seahorse
sites.”
Agilent and Seahorse are in the early stages
of “integration planning” while they continue to operate as two separate companies until
the transaction is finalized.
Since spinning off its electronic measurement business Keysight Technologies on Nov.
1, 2014, the “new Agilent” has finally been
in a position to focus exclusively on the life
This month’s Q&A, “Big data
for oncology,” gave DDNews
Managing Editor Lloyd Dunlap
a chance to converse with Dr.
William Dalton, CEO of M2Gen
at Moffitt Cancer Center, and
Dr. Michael A. Caligiuri, CEO of
James Cancer Hospital and Solove
Research Institute and director of
the OSU Comprehensive Cancer
Center. To read it, just go to our
website and search for the
Editconnect number: E101536.
CREDIT: AGILENT TECHNOLOGIES
Agilent plans to acquire Seahorse Biosciences for $235 million in its quest to not simply focus
on life sciences, diagnostics and applied chemicals, but to be the top player in the analytical
labs marketplace and in targeted clinical research and diagnostic segments.
sciences, diagnostics and applied chemical
markets, Drake says.
“The company is operating with clearly
defined strategic priorities, aimed at meeting the needs of our customers and generating value for our shareholders,” Drake
continues. “Agilent has moved quickly over
the past several months to refine its portfolio and realign the organization for growth.
Agilent has a strong and experienced leadership team, headed by Mike McMullen,
who became CEO in March 2015. Under
Mike’s leadership, Agilent is focusing on
expanding its success in analytical laboratories to life-science solutions and diagnostics markets.”
Agilent’s vision is “to be No. 1 in the
analytical labs marketplace and in targeted
clinical research and diagnostic segments,”
she explains. “We want to collaborate with
our customers to empower breakthrough
research and ultimately, support discoveries
that advance the quality of life.”
Seahorse execs opted not to speak to media
while the final acquisition agreement is pending. However, in a news release, Jay Teich,
CEO of Seahorse Bioscience, stated, “We
are proud to have enabled the exploration of
bioenergetics in living cells by nearly 10,000
scientists worldwide, and to have created a
new category of cell-based assay tools.”
“Joining Agilent, a premier, customerfocused supplier of technology to a much
broader market, will give many more
researchers access to Seahorse tools,” Teich
added. “And when these two technologyrich companies combine, we expect to offer
a series of new products and applications that
will benefit our customers.”
Privately held Seahorse Bioscience,
founded in 2001, is headquartered in Billerica, Mass., with manufacturing operations
in Chicopee, Mass., and regional offices in
Copenhagen, Denmark and Shanghai.
In other recent news (also noted on page
42), Agilent announced a different kind
of collaboration with Dr. Steven Gross of
Weill Cornell Medical College to advance
research in amyotrophic lateral sclerosis,
also known as Lou Gehrig’s disease. Agilent
will provide the latest mass spectrometry
technology to support his research, working
toward an understanding of how the most
common form of this disease develops in
the body.
The Agilent 6230B LC TOF and 6550A LC
Q-TOF mass spectrometers will be housed in
the laboratory of Gross, an internationally
recognized expert in the use of mass spectrometry-based metabolomics. His expertise
is in pharmacology and cell biology, particularly in relation to the role of nitric oxide as
a signaling molecule.
ALS is a deadly and progressive
neurodegenerative disease that affects nerve
cells in the brain and spinal cord, and is also
characterized by impaired metabolic control.
Sporadic amyotrophic lateral sclerosis
(sALS) accounts for about 90 percent of all
ALS cases and has no obvious genetic driver.
Gross and his collaborators—Dr. Giovanni
Manfredi, a professor of neuroscience in the
Feil Family Brain and Mind Research Institute at Weill Cornell and Dr. Lorenz Studer,
director of Sloan Kettering Institute’s Center for Stem Cell Biology—are investigating
the molecular underpinnings of this form
of ALS.
The Agilent tools will empower the
investigators to apply a multidisciplinary
approach to understanding the roots of
this disease, the company said. Accuratemass mass spectrometry will enable these
researchers to test the hypothesis that fibroblasts express systemic metabolic markers
that inform ALS.
“Translational research using a combination of biological disciplines—genomics, proteomics, transcriptomics, metabolomics—is
an emerging trend in academia,” said Steven
Fischer, Agilent’s market director for life-science research in academia and government.
“Most researchers, however, do not know
how to perform multi-omic analysis, and
successful examples are needed. Agilent is
working with the Gross lab at Weill Cornell
to advance the multi-omics-based approach
to disease research, using sporadic ALS to
demonstrate the power of this method. We
anticipate that this scientific work with
Agilent will continue into the future as we
apply multi-omics approaches to other poorly understood diseases with unmet clinical
needs,” he added. n
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The best of the research biology community will be gathering in San
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APPROVAL
Taiho Oncology announces
FDA approval of Lonsurf
PRINCETON, N.J.—Taiho Oncology Inc. (U.S.), a sub-
sidiary of Taiho Pharmaceutical Co. Ltd. in Japan,
announced in late September that the FDA had
approved Lonsurf (trifluridine and tipiracil), formerly
known as TAS-102, for the treatment of patients with
metastatic colorectal cancer who have been previously
treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological
therapy and, if RAS wild-type, an anti-EGFR therapy.
“Patients with metastatic colorectal cancer, whose
disease has progressed after treatment with standard
therapies, have had limited therapeutic options to
treat their disease,” said Eric Benn, Taiho Oncology’s
president and CEO. “Lonsurf helps address this unmet
medical need by providing patients with a new therapeutic option that can help extend their overall survival.
As the first FDA approval for Taiho Oncology, Lonsurf
also represents a major milestone for our company.”
“Metastatic colorectal cancer cells often become resistant to previously effective treatment,
underscoring the importance of identifying new
therapeutic options for patients with the disease,”
said Dr. Robert J. Mayer, faculty vice president for
academic affairs at the Dana Farber Cancer Institute,
professor of medicine at Harvard Medical School,
and principal investigator of the RECOURSE trial that
studied the compound. “In a pivotal clinical trial,
Lonsurf demonstrated that it can extend overall
survival, providing patients and their oncologists
with a novel oral therapy.”
Lonsurf was approved in Japan in March 2014 and
is indicated to treat unresectable advanced or recurrent colorectal cancer.
EMA fast-tracks antidote to
anticoagulant Pradaxa
INGELHEIM, Germany—The European Medicines Agency
(EMA) recently recommended granting a marketing
authorization, following accelerated assessment,
for Boehringer Ingelheim’s Praxbind (idarucizumab)
as a specific antidote to the anticoagulant medicine
Pradaxa (dabigatran etexilate), when rapid reversal of
its effect is required. Praxbind is to be used when a
patient taking Pradaxa needs to undergo an emergency surgery or when life-threatening or uncontrolled
bleeding occurs.
Pradaxa belongs to a new generation of oral anticoagulants approved over the past few years, which
have given doctors and patients a wider range of
options to prevent and treat thromboembolic disor-
CREDIT: BOEHRINGER INGELHEIM
sufentanil sublingual tablets) for the management of
acute moderate-to-severe postoperative pain in adult
patients. The marketing authorization is granted for
the 28 EU member states as well as for the European
Economic Area (EEA) countries of Norway, Iceland and
Liechtenstein. Zalviso is a system combining a drug
and a device designed to deliver a sublingual tablet
formulation of sufentanil via a proprietary, preprogrammed, noninvasive, patient-controlled analgesia
device. Grunenthal Group, AcelRx’s licensee in Europe
and Australia, expects the product to be available to
Western European patients in the first half of 2016.
“This is a significant event for AcelRx. Not only
is this the company’s first marketing approval, but it
represents the successful development and commercialization of a product that we believe will provide
a new way for physicians and their patients to treat
acute moderate-to-severe postoperative pain using
an innovative delivery method,” stated Howie Rosen,
interim CEO of AcelRx Pharmaceuticals. “Our partner
Grunenthal will be working with the member states
of the EU and EEA to ensure that Zalviso is made
available to those patients who would benefit from
an effective and reliable solution for their moderateto-severe postsurgical pain.”
Boehringer Ingelheim’s Praxbind, an antidote
for the anticoagulant Pradaxa when
emergency bleeding occurs, recently got fasttracked by the European Medicines Agency.
Pictured here is a Boehringer Ingelheim
biopharmaceutical operation.
ders in adults. Praxbind is the first medicine designed
to specifically neutralize the anticoagulant effect of
Pradaxa.
Bleeding is a well-known complication of all anticoagulants, and information on how to address this
risk has been included in Pradaxa’s product information since it was first authorized in the European
Union (EU) in March 2008. Although low in frequency
in patients treated with Pradaxa, major and sometimes life-threatening bleeding may occur. However,
unlike older oral anticoagulants such as warfarin, up
until now there has been no specific means of rapidly
neutralizing Pradaxa’s effect.
The QIDP designation was created by the Generating Antibiotic Incentives Now (GAIN) Act of 2012. It
provides certain incentives for the development of
new anti-infectives, including eligibility for priority
review, the FDA’s Fast Track program and a five-year
extension of exclusivity under the Hatch-Waxman Act.
Cempra is developing Taksta exclusively in the
United States for ABSSSI and is exploring its use for
the long-term oral treatment of refractory bone and
joint infections, including prosthetic joint infections.
Fusidic acid is orally active against gram-positive
bacteria, including all Staphylococcus aureus strains,
such as HA-MRSA and CA-MRSA.
PARTNER
15 that the FDA had approved Nuwiq, Antihemophilic Factor (Recombinant), an intravenous therapy
for adults and children living with hemophilia A. The
Nuwiq approval includes on-demand treatment and
control of bleeding episodes, routine prophylaxis to
reduce the frequency of bleeding episodes and perioperative management of bleeding.
Nuwiq is the first B-domain deleted recombinant
factor VIII (FVIII) derived from a human cell line, not
chemically modified or fused with another protein,
designed for the treatment of patients with hemophilia A, congenital FVIII deficiency. Although present therapies for hemophilia A treatment exist in the
United States, significant challenges still remain,
including development of inhibitors and the need for
multiple infusions on a prophylactic basis.
“Octapharma has been committed to the bleeding
disorders community for many years, and its decadelong drive to find solutions for hemophilia A challenges has never wavered,” said Octapharma USA
President Flemming Nielsen. n
tary skin permeation enhancer” that
functions by loosening the tight junctions of skin cells.
In 2012, Apricus shared data from its
Phase 3, randomized, double-blind study
of Femprox at the 2012 World Meeting
on Sexual Medicine, with Dr. Irwin
Goldstein, director of sexual medicine
at the Alvarado Hospital in San Diego
and a member of Apricus’ Femprox clinical advisory board, presenting the data.
Slides from the presentation relayed
that the study consisted of women with
FSIAD ages 22 to 65, with a primary
efficacy endpoint of satisfactory sexual
events and secondary efficacy endpoint
of the Female Sexual Function Index,
Female Sexual Distress Score and global
assessment question. At a dose of 900
mcg, Femprox demonstrated clinically
significant improvement over placebo
in all primary and secondary endpoints.
Apricus’ other pipeline products
include fispemifene, a Phase 2 selective estrogen receptor modulator for
the treatment of symptomatic male
secondary hypogonadism, and RayVa,
a Phase 2 product candidate for the treatment of Raynaud’s disease. Raynaud’s
is a circulatory disorder that affects the
blood vessels, causing some areas of
the body, such as the hands or feet, to
feel numb or cold and sometimes turn
white in response to cold temperatures
or stress. Apricus has begun a Phase 2b
trial for fispemifene, with additional
studies planned in other urological
conditions, and enrollment was recently
completed for a Phase 2a trial of RayVa.
On the commercial side, Apricus’
lead product is Vitaros, an erectile
dysfunction treatment approved in
Canada and Europe. The company recently announced a license agreement in
which it secured the U.S. development
and commercialization rights for Vitaros
from Allergan. Warner Chilcott, which
is now a subsidiary of Allergan, acquired
the U.S. rights to Vitaros in February
2009. Under the terms of this agreement, Apricus will assume responsibility for all Vitaros development efforts
in the United States, and should the
U.S. Food and Drug Administration
accept an NDA for Vitaros, Allergan
can choose to exercise its one-time
opt-in right to assume all future marketing and selling activities in the United
States in exchange for certain financial
considerations. Should Allergan exercise
that right, Apricus stands to receive up
to a total of $25 million in upfront and
potential launch milestone payments, as
well as a double-digit royalty on net sales
of Vitaros. If Allergan doesn’t exercise its
option, Apricus can commercialize Vitaros and will pay Allergan a double-digit
royalty on net sales of the product. The
agreement stipulates that in return for
the development and commercialization
rights, Apricus paid Allergan $1 million
up front, with Allergan eligible to also
receive a future $1.5-million regulatory
milestone payment. Allergan also retains
the right to launch a future authorized
generic under a profit-share structure
with Apricus. n
New medicine to treat heart failure
recommended for approval
BASEL, Switzerland—The EMA’s Committee for Medicinal Products for Human Use recently recommended
granting a marketing authorization for Novartis’
Entresto (sacubitril/valsartan) for adults with symptomatic chronic heart failure with reduced ejection
fraction, a condition where the heart muscle does
not contract effectively and less oxygen-rich blood
is pumped out to the body. Around half of people
with heart failure will have reduced ejection fraction.
Entresto is a combination of valsartan (an angiotensin receptor blocker, or ARB) and sacubitril. Sacubitril is the first in a new class of medicines called
neprilysin inhibitors. Entresto works in two ways—
FDA grants Fast Track Designation to
MDX for Fragile X Syndrome
TEL AVIV, Israel—Alcobra Ltd., an emerging pharma-
ceutical company focused on the development of
new medications to help patients with cognitive
disorders, including attention deficit hyperactivity
disorder (ADHD) and fragile X syndrome, announced
recently that the FDA had granted Fast Track designation to Metadoxine Extended Release (MDX) for the
treatment of fragile X syndrome.
“We are pleased that the FDA has recognized the
potential of MDX in fragile X syndrome and granted
Fast Track designation for this indication,” said Dr.
Yaron Daniely, president and CEO of Alcobra. “We
look forward to our upcoming meeting with the FDA
to determine next steps in advancing the development
program for MDX in this area of serious unmet
medical need.”
Companies that receive Fast Track designation
can have more frequent interactions with the FDA
review team to facilitate product development. In
addition, based on clinical data, the NDA applications for these products could be eligible for priority
and/or rolling review.
In 2013, the FDA granted orphan status to metadoxine for the treatment of fragile X syndrome, a condition for which there are currently no FDA-approved
medications.
QIDP status goes to Taksta antibiotic
CHAPEL HILL, N.C.—Mid-September saw Cempra Inc.,
a clinical-stage pharmaceutical company focused on
developing antibiotics to meet critical medical needs
in the treatment of bacterial infectious diseases,
announce that the FDA had granted a qualified infectious disease product (QIDP) designation to Cempra’s
investigational antibiotic product candidate, Taksta
(CEM-102, sodium fusidate, the sodium salt of fusidic
acid). The designation is for Taksta oral tablets for the
indication of acute bacterial skin and skin structure
infections (ABSSSI).
“Taksta is Cempra’s second antibiotic product candidate to obtain QIDP status, which should enable us
to expedite its development and bring this promising
drug to the patients who need it the most,” said Dr.
Prabhavathi Fernandes, president and CEO of Cempra.
“Previously our lead product, solithromycin, received
QIDP status, and together we view these designations as further validation of Cempra’s progress in
achieving its goal of becoming a leader in the global
anti-infective market.”
CREDIT: NOVARTIS
Novartis’ Entresto for treatment of heart failure
got recommendation for approval by the
Committee for Medicinal Products for Human
Use of the European Medicines Agency.
valsartan blocks the angiotensin II type-1 receptor,
suppressing the harmful effects of angiotensin II on
the cardiovascular system, while sacubitril blocks an
enzyme known as neprilysin to enhance the protective
neurohormonal systems of the heart.
The efficacy of Entresto compared with enalapril
(an ACE inhibitor) was assessed in one randomized
controlled trial including over 8,000 adults with heart
failure with reduced ejection fraction. Patients also
received other heart-failure medicines. The trial was
stopped early when it was found that Entresto was
more effective than enalapril in reducing deaths from
cardiovascular disease.
FDA approves Nuwiq for hemophilia A
HOBOKEN, N.J.—Octapharma USA announced Sept.
TOTAL
tions can be rapidly selected, expediting product development timelines, according to the company.
Kapa’s por tfolio of NGS
reagents includes enzymes such
as novel DNA polymerases,
with the potential to improve
the performance of the entire
sequencing workflow. The objective is to develop innovative solutions that accelerate genomics
research that can impact the future
ability to diagnose, monitor and
treat cancer and complex inherited
and infectious diseases.
Founded by Trey Foskett, Paul
McEwan, Ron McEwan and Chris
McGuinness in 2006, Kapa Biosystems uses what it calls “directed
evolution” to develop reagents for
life-sciences applications. Directed
evolution, a method of protein
engineering that simulates natural
selection in the lab, starts with a
gene coding for a “wild-type,” or
unmodified, enzyme of interest.
Random variation is introduced
into the gene by mutagenesis,
generating a library of millions
of genes each coding for a unique
enzyme variant. A functional
selection pressure is then applied
to the library, and only the genes
coding for the highest performing
enzymes “survive.” This process of
random mutation and selection is
repeated until the desired enzyme
characteristic evolves.
“This acquisition builds on
Roche’s commitment to develop a
differentiated NGS portfolio that
will provide our customers with a
complete genetic testing solution,”
according to Roland Diggelmann,
chief operating officer of the Roche
Diagnostics Division. “Kapa’s technology and products complement
our current expertise and offerings such as the portfolio of target
enrichment products for NGS. We
welcome Kapa’s employees and are
looking forward to strengthening
our NGS offerings with this unique
technology.”
In February, Roche acquired
Signature Diagnostics, a privately
held company based in Potsdam,
Germany, to advance translational research for NGS diagnostics. Roche plans to leverage
Signature’s expertise in biobanks
and NGS assays to develop novel
diagnostics for cancer patients.
Signature is a translational oncology and genomics company that
develops large blood plasma and
tissue biobanks in multiple cancers, including colorectal and
lung, which are constructed from
multicenter prospective clinical
studies. As Diggelmann explains,
“Signature represents a unique
bridge between high-value cancer
biobanks and NGS assay development. Roche plans to leverage Signature’s expertise in both of these
areas to accelerate the development
of targeted NGS-based diagnostics
in the future. Biobanks can also be
used for biomarker discovery and
hypothesis testing with pharma.”
Getting back to the current deal,
Paul McEwan, co-founder and
chief scientific officer of Kapa Biosystems, said in an official statement that “Joining Roche provides
us access to their broad product
portfolio, global reach and clinical
expertise that will accelerate our
strategy of offering comprehensive
NGS workflow solutions to more
laboratories around the world.
We are also excited to have the
opportunity to further leverage our
enzyme engineering capabilities
to advance the fields of genomics
and sequencing, with the ultimate
goal of having a more significant
impact on medicine and human
health.”
Roche, a leader in researchfocused healthcare in pharmac e u t i c a l s a n d d i a g n o s t i c s,
offers medicines in oncology,
immunology, infectious diseases,
ophthalmology and neuro science. It cites itself as a world
leader in in-vitro diagnostics and
tissue-based cancer diagnostics
and as a frontrunner in diabetes
management.
Founded in 1896, Roche has been
making important contributions
to global health for more than a
century. Twenty-nine medicines
developed by Roche are included
in the World Health Organization
Model Lists of Essential Medicines,
among them life-saving antibiotics,
antimalarials and chemotherapy.
Roche’s personalized healthcare str-
ategy aims at providing medicines
and diagnostics that enable tangible
improvements in the health, quality of life and survival of patients. In
2014, the Roche Group employed
88,500 people worldwide, invested
8.9 billion Swiss francs in R&D and
posted sales of 47.5 billion Swiss
francs. Genentech, in the United
States, is a wholly owned member
of the Roche Group. Roche is also
the majority shareholder in Chugai
Pharmaceutical in Japan. n
WATCH SLAS2016.ORG
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F E AT U R E D P R O D U C T
AutoGen introduces first and only precipitationchemistry system that fully automates whole-blood DNA
isolation from primary tubes to final DNA storage tubes
PRODUCTS & SERVICES
Combine the power
of digital PCR with
multiplex technology
Bio-Rad Laboratories
ADVERTISER ’S INDEX
Affymetrix.................................................................3, 33 www.affymetrix.com
ASCB (American Society for Cell Biology)..........43 www.ascb.org
AutoGen Inc.
Asterand Bioscience.................................................21 www.asterand.com
In a single,
compact
package,
FlexSTAR+
completely
automates the
whole-blood
DNA extraction
process from
primary tube
sampling to
final DNA
elution into
storage tubes. What truly distinguishes FlexSTAR+ from other DNA
extraction solutions is its chemistry. Unlike many other systems,
FlexSTAR+ features Qiagen’s FlexiGene chemistry—robust, reliable
precipitation chemistry that produces cleaner, longer-stranded DNA for
long-term storage.
AutoGen Inc.
www.autogen.com
Beckman Coulter International...............................31 www.beckmancoulter.com
Bio-Rad Laboratories, Inc.........................................48 www.bio-rad.com
Biosearch Technologies, Inc...................................47 www.biosearchtech.com
BioTek Instruments, Inc............................................25 www.biotek.com
Cambridge Healthtech Institute..............................39 www.healthtech.com
Charles River Laboratories, Inc................................. 5 www.criver.com
Detect seven of the most common KRAS
mutations in a single Droplet Digital
PCR (ddPCR) experiment with Bio-Rad’s
ddPCR KRAS Screening Multiplex Kit.
These fully wet-lab validated, probebased assays can detect mutations at
frequencies as low as 0.2 percent. Visit
bio-rad.com/info/kras to see how you
can save time and precious sample by
multiplexing your ddPCR experiments.
Bio-Rad Laboratories
www.bio-rad.com/info/kras
Covance.......................................................................... 2 www.covance.com
Viable tumor samples
for in-vivo and ex-vivo
oncology R&D
Video shows unique features
of multichannel pipette
reagent reservoirs
ImageXpress system expands
the boundaries of research
Easily automated 3D
cell culture growth
Crown Bioscience Inc.
INTEGRA
Molecular Devices
AMSBIO
Crown Bioscience offers access to
the world’s largest bank of viable
cryopreserved tumor cells, including:
•100,000+ samples
•25+ tissue types, 76+ clinical
diagnoses
•Oncology drug tested samples
•Virtually all common and rare cancer
indications
The bank was collected over the past
20 years from a U.S. population, with
matched histology/path review and
associated ex-vivo treatment data for
each specimen.
Crown Bioscience Inc.
www.crownbio.com/products/
tumor-samples
When watching this video you will learn
about how INTEGRA 10 ml, 25 ml and
100 ml multichannel reagent reservoirs
are designed to nest inside each other,
making it possible to get twice as many
reservoirs in half the space of other
products, reducing inventory space
requirements and shipping costs.
INTEGRA reservoirs are made of
crystal-clear polystyrene and fit into a
reusable base with bold, crisp, clearly
visible graduation markings. This
unique design allows for more accurate
measurement of reagents.
INTEGRA
www.integra-biosciences.com/sites/
video/simpleshow-reservoir.html
New products for exosome
isolation to mRNA
purification
Innova Biosciences
introduces range of
conjugated antibodies
Hitachi Chemical
Diagnostics Inc.
Innova Biosciences
Pall ForteBio Launches the
Octet K2 System, Increasing
Access to Sensitive Binding
Interactions Analysis
Your partner in CNS
discoveries
Charles River
Charles River provides central
nervous system (CNS) research tools
and services from drug discovery to
IND-enabling studies. Our validated
preclinical models and full-service
CNS drug discovery capabilities
include in-vivo imaging, behavioral
and biomarker readouts covering all
aspects of acute and chronic neurology,
psychiatry, pain, neuromuscular disease
and rare diseases. Tailored study
designs, longitudinal testing modalities,
high-throughput screening, extensive
surgical capabilities and seamless
program transition from discovery to
safety make Charles River your partner
in CNS discoveries.
Charles River
www.criver.com/neuroscience2015
The ExoComplete
96-Well Plate Kit
and ExoComplete
Tube Kit is
an integrated, fast and easy system
for exosome collection to mRNA
purification. The ExoComplete system
isolates exosomal mRNA from biological
samples such as plasma in a 96-well
filter plate format, or large-volume
samples such as urine in a single
collection tube format. Exosomes
and microvesicles (EMVs) in body
fluids are captured with Hitachi
Chemical’s Exosome Isolation Plate
or Exosome Collection Tube with a
proprietary filter material. The highly
porous material allows fast filtration of
biological samples without clogging and
reproducible isolation of EMVs without
conventional ultracentrifugation.
Hitachi Chemical Diagnostics Inc.
www.hcdiagnostics.com
Innova Biosciences’ unique new
range of conjugated antibodies
leverages the company’s LightningLink and InnovaCoat bioconjugation
technologies. The range comprises 200
antibodies to nearly 30 different cardiac
biomarkers, each available directly
conjugated to 24 different enzymes,
fluorescent dyes or nanoparticles.
Innova Biosciences
https://www.innovabiosciences.com/
products/antibody-conjugates
Pall Life Sciences
Today, we are
happy to support
the release of
Pall ForteBio’s
Octet K2 system.
This smallcapacity assay
testing system is sized and priced for
early research and discovery, catered
particularly to academic and small
biotech laboratories. Now available
globally, the Octet K2 system offers
high-performance, budget-friendly
kinetic characterization of antibody,
protein and small-molecule binding
interactions.
Pall Life Sciences
www.impresslabs.com
INDIGO Biosciences..................................................19 www.indigobiosciences.com
INTEGRA Biosciences AG.......................................... 7 www.integra-biosciences.com
OriGene Technologies, Inc................................ Cover www.origene.com
Plas-Labs, Inc..............................................................27 www.plas-labs.com
R&D Systems, Inc.......................................................13 www.RnDSystems.com
Roche Applied Science............................................17 www.roche-applied-science.com
SLAS 2016.....................................................................45 www.slas2016.org
Swift Biosciences........................................................ 9 www.swiftbiosci.com
Thermo Fisher Scientific........................ 14, 15, 23, 37 www.thermoscientific.com
The ImageXpress Micro Confocal
High-Content Imaging System captures
publication-grade images with the
widest range of objective lenses,
allowing you to work at the resolution
appropriate for your biology—at a
speed you would only expect from
widefield screening. A quick switch
between confocal and widefield modes
satisfies the specific throughput
and sensitivity needs for your assay.
Explore thick tissues, spheroids,
organisms and more.
Molecular Devices
www.moleculardevices.com
Compatible
with automated
handling
and imaging
equipment,
Mimetix scaffold is incorporated
into standard ANSI / SLAS footprint
microplate frames with superior optical
clarity and minimal base distortion. The
scaffold depth of 50 µm is thick enough
to provide the benefits of 3D cell culture,
yet thin enough to allow fluorescent and
light microscopic imaging. Mimetix has
been validated with a number of primary
cells, cell lines and stem cells.
Mimetix scaffolds mimic the
extracellular matrix by providing an
ideal architectural environment to
support the growth of cells in 3D.
Mimetix scaffolds are free from animalderived products and are created by
electrospinning medical-grade polymer
poly(L-lactide) into microfibers.
AMSBIO
www.amsbio.co.uk/mimetix.aspx
Tools for post-purification
sample handling
Genevac
For labs
undertaking
purification
using normal
phase HPLC,
SFC or flash chromatography, removal
of organic solvents can be simply,
productively and safely carried out in a
Genevac centrifugal evaporator (EZ-2,
ROCKET, Rocket Synergy or HT Series
III). Where the nature of the sample
being concentrated can lead to solvent
bumping, Genevac’s DriPure technology
eliminates this troublesome and timeconsuming problem. A multiple-stage
method allows the EZ-2 evaporator to
remove organic solvent without freezing
the water, remove the water and then dry
any remaining stubborn solvent. Also,
the LyoSpeed method can be used in
Genevac HT evaporators to produce dry
powders from samples that previously
could only be produced as gums and oils.
Genevac
www.genevac.com/purification
New chiral phase for
HPLC and SFC analysis and
purification work
Phenomenex
The Lux Amylose-1 column for HPLC
and SFC is a new high-efficiency
chiral stationary phase. The
affordable Amylose-1 adds valuable
enantioselectivity to the Lux column
family with the chiral selector amylose
tris (3,5-dimethylphenylcarbamate) and
is a guaranteed alternative to other
phases with the same chiral selector.
Offered in 5 µm particles, the new media
is available in analytical columns and
Phenomenex-patented Axia preparative
column hardware.
Phenomenex
www.phenomenex.com/lux
We’re fluent in the language of
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If you need to source
custom, GMP compliant
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BIO-RAD’S DROPLET DIGITAL™ PCR SYSTEMS
Over 250 Peer-Reviewed Droplet Digital PCR (ddPCR™ ) Publications*
From detection of rare mutations and cancer biomarkers to quantification of gene editing events
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*Based on PubMed data, July 2015.
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