1. health and fitness
2. disease
3. autism and pdd

PHARMA, BIOTECH & LIFE SCIENCE
WHAT’S INSIDE
DISCOVERY6
RESEARCH & DEVELOPMENT
12
PRECLINICAL16
CLINICAL TRIALS
25
JANUARY 2015 : VOLUME 11 : NUMBER 1
PUBLISHED SINCE 2005
01.15
Merck to pay $8.4 billion for Cubist
Merck cites leadership in
anti-infectives and
identification of hospital
acute care as a priority area
BY JEFFREY BOULEY
WHITEHOUSE STATION, N.J.—Antibiotics
haven’t been what one would call a priority for Big Pharma lately, given the fact they
BUSINESS & GOVERNMENT POLICY
33
don’t lend themselves as well to blockbuster
status compared to many other therapeutic
TOOLS & TECHNOLOGY
areas. However, that doesn’t seem to be stopPreferred tox partner...........................................................12
ping Merck & Co., known as MSD outside
Nanofiber vs. HIV.................................................................14
the United States and Canada, from making a
On ‘cloud 9’ with new mobile health app........................25
Alion taps MPI for companion diagnostic.......................26
pricey and, to some, risky decision to acquire
On the cutting edge.............................................................34
Lexington, Mass.-based Cubist Pharmaceuticals Inc. for $102 per share in cash, a 35-perFINANCE/MARKETS3
cent premium to Cubist’s average stock price
EDITORIAL/COMMENTARY10
for the most recent five trading days at the
time of the early-December announcement.
AWARDS & HONORS
37
This makes for an equity valuation of $8.4
PRODUCTS & SERVICES
38
billion, but the deal also includes the assumpQ&A39
tion of $1.1 billion in net debt and other
putting the total transaction
SOCIETY FOR LABORATORY
20 considerations,
AUTOMATION AND SCREENING
value at around $9.5 billion.
4th Annual Conference and Exhibition
The boards of directors for both companies
Washington, D.C., will host
have weighed in with their approval of the
“what’s new in lab automation and
screening” at SLAS2015
deal, and the companies expect the transac-
DIAGNOSTICS30
tion to close in the first quarter of this year.
The acquisition of Cubist will create what
Merck calls a “strong fundamental value
with return on capital in excess of Merck’s
hurdle rate within a few years of closing,” and
the company expects the acquisition to add
more than $1 billion of revenue to its 2015
base. In the end, the transaction will likely
be neutral to non-GAAP EPS in 2015, Merck
acknowledged, though it expects the deal
to be significantly accretive to non-GAAP
EPS in 2016 and beyond, with these gains
expected to appear in both Merck’s sales and
earnings growth.
Cubist’s pipeline and abilities reportedly
complement Merck’s strategy and the global
initiative the company launched last year,
particularly in the area of “sharpening its
commercial focus on key therapeutic areas
that have the potential to deliver the greatest
return on investment.” Merck leaders maintain that with the company’s longstanding
leadership in anti-infectives, as well as its
customer-focused operating model, it was
natural to identify the hospital acute-care
segment as one of the company’s key priority areas and one in which Merck maintains
CUBIST CONTINUED ON PAGE 36
Although Cubist (pictured here) is facing legal
challenges that could force it to face generic
competition for its lead drug, Cubicin, four
years earlier than planned, Merck is ready to
pay $8.4 billion for the company and assume
some $1.1 billion in debt.
Two partners, three
initiatives, five years
Evotec and Sanofi forge
three-part deal to improve
innovation in drug discovery
and preclinical development
BY KELSEY KAUSTINEN AND JEFFREY BOULEY
Unlike current treatments for multiple sclerosis, which focus on reducing the frequency of
relapses, GeNeuro’s drug holds the potential to stop progression of the disease altogether.
Targeting MS at its root
Servier and GeNeuro to
advance drug offering
new approach to treating
multiple sclerosis
BY ZACK ANCHORS
SURESNES, France— A deal struck
between Servier and the Swiss biotech
firm GeNeuro will push forward the
development of a drug that offers a new
approach toward the treatment of multiple sclerosis (MS). Servier has agreed
to fund the development and marketing
of GeNeuro’s drug candidate GNbAC1 to
target a protein believed to play a key role
in causing MS.
“This drug offers a completely new way
to treat MS,” GeNeuro CEO Francois Curtin tells DDNews. “GNbAC1 targets the
protein MSRV-ENv, a factor that strong
evidence shows to be a causal. This is the
first treatment targeting this factor.”
Servier will provide GeNeuro $47
million for the completion of Phase 2b
trials as the first stage in a deal that provides
a framework for the global development
and licensing of the drug. Following Phase
2b trials, Servier will have the option to
license the drug in all markets except the
United Staes and Japan. Servier will cover
Phase 3 global development costs and pay
GeNeuro up to $408 million in future
development and sales milestones, in
GENEURO CONTINUED ON PAGE 29
HAMBURG, Germany—Evotec AG and Sano-
fi have begun exclusive negotiations for a
major multi-component strategic alliance
focused on early-stage drug development
that could run over the next five years. The
collaboration will consist of three major
strategic initiatives focused on improving
innovation effectiveness in the drug discovery and preclinical development space. Evotec also expects this undertaking to bolster
its position as “the leading drug discovery
EARLY CONTINUED ON PAGE 9
Sanofi’s small-molecule library, established
on its Toulouse R&D site, has over one million
compounds and will greatly boost Evotec’s
library of more than 400,000 compounds once
Evotec takes over the Toulouse site.
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FINANCE
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JANUARY 2015 | | DDNEWS 3
Promethera raises $31.4 million in Series C financial round
MONT-SAINT-GUIBERT, Belgium—
Promethera Biosciences, a biotechnology company developing Promethera HepaStem, a cell-based therapy
for the treatment of in-born errors
of metabolism and acquired liver
diseases, recently announced the
completion of its Series C fundraising round. The company has raised
€25.33 million (about $31.4 million),
including €20.33 million in capital.
The success of the Series C fundraising is considered to be the result
of the completion of the HepaStem
Phase 1/2 study, following a Series
B fundraising in March 2012 when
€17 million in equity was raised.
The financing round was supported by existing Promethera
Biosciences investors and two new
investors: SFPI-FPIM, the Belgian
Federal Holding and Investment
Company, and SMS Investments, a
Luxemburg-based subsidiary office
Oramed closes
$5M investment
from Guangxi
JERUSALEM—Oramed
Pharmaceuticals Inc., a developer
of oral drug delivery systems, today
announced that it has received $5
million in connection with the
definitive agreement with Guangxi
Wuzhou Pharmaceutical Co. Ltd.
previously reported on Nov. 3 for
the purchase of 696,378 restricted
shares of common stock for $7.18
per share, the closing price of
Oramed’s common stock on Oct.
31 in a private placement.
“We are pleased to have Wuzhou
as a new shareholder,” noted Nadav
Kidron, CEO of Oramed. “China
offers a substantial market opportunity for our diabetes-focused
pipeline, and we are delighted to
have Wuzhou as a supportive shareholder, as they can help strategically guide our development and
commercial entrance into China.”
Oramed intends to use the net
proceeds from this offering for
expenses primarily related to the
company’s anticipated U.S.-focused
clinical development programs for
its oral insulin for type 1 and type 2
diabetes indications, for preclinical
and clinical studies of its oral GLP-1
analog project and for general corporate purposes, including general
working capital purposes.
Oramed is seeking to revolutionize the treatment of diabetes
through its flagship product, an
orally ingestible insulin capsule
(ORMD-0801). Having completed
separate Phase 2a clinical trials, the
company anticipates the initiation
of separate Phase 2b clinical trials
in patients with both type 1 and
type 2 diabetes under an Investigational New Drug application with
the U.S. Food and Drug Administration. In addition, the company
is developing an oral GLP-1 analog
capsule (ORMD-0901). n
of the German SMS group. They
join the company’s historical international investors: Vesalius Biocapital and Boehringer Ingelheim
Venture Fund (the venture capital
fund of the German pharmaceutical
group), the lead investors; SRIW;
Shire; Mitsui Global Investment,
the venture capital fund of Japanese
industrial conglomerate Mitsui &
Co Ltd. and Pall-ATMI LifeSciences;
Vives-Louvain Technology Transfer
Office Fund; as well as several business angels.
In addition, the Walloon region,
which has backed the company
since its inception, has granted
loans and subsidies of €5 million
to support the clinical development
of HepaStem and the collaborative
program with EMD Millipore.
“We have made substantial progress and obtained significant achievements during the past three years,
including the successful completion
of our Phase 1/2 clinical trial with
Promethera HepaStem in urea cycle
disorders and Crigler-Najjar disease.
The study provided positive safety
and preliminary efficacy data that
enabled us to pursue the development of these indications. In addition, we have already obtained the
first authorization for the HEP002
study, a Phase 2b/3 clinical trial in
urea cycle disorders,” said Eric Hali-
oua, CEO of Promethera Biosciences.
“We are hopeful that Promethera’s
technology will shift the treatment
paradigm for patients living with
orphan liver diseases. We see a lot
of interest from healthcare professionals who are eager to see this
innovative therapy become a reality
to support patients with high unmet
medical needs,” added Prof. Etienne
Sokal, chief scientific officer and
founder of Promethera Biosciences. n
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MARKETS
4 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
Pharmaceutical and biotech market indices
T
Amex Pharmaceutical Index
he burrill select index rose 1.17
percent in November, less than the
modest gains posted by the major
market indices. The Dow Jones
Industrial Average rose 2.52 percent,
the Standard & Poor’s 500 gained 2.45 percent
and the Nasdaq Composite Index finished the
month up 3.47 percent.
465
03/Jan
492
495
14/Feb
14/Mar
481
11/Apr
505
512
522
09/May
13/Jun
11/Jul
551
524
533
531
29/Aug
30/Sep
31/Oct
28/Nov
1151
1222
1236
1144
15/Aug 29/Aug
30/Sep
31/Oct
28/Nov
506
15/Aug
SOURCE: YAHOO FINANCE
Burrill Select
Burrill Mid-Cap Biotech and Small-Cap Biotech
533
586
257
576
497
505
207
184
14/Feb
11/Apr
09/May
553
567
215
197
220
13/Jun
11/Jul
610
696
666
1105
1090
946
941
963
1036
1076
1116
300
145
03/Jan
552
621
14/Mar
MID -C AP
225
218
15/Aug 29/Aug
30/Sep
243
31/Oct
218
03/Jan
28/Nov
14/Feb
14/Mar
11/Apr
09/May 13/Jun
11/Jul
SMA L L- CA P
SOURCE: BURRILL & CO.
SOURCE: BURRILL & CO.
Costs of M&As rise as environment becomes more competitive
BY BURRILL MEDIA
SAN FRANCISCO—The merger and acquisi-
tion (M&A) deal signed by Actavis to acquire
Botox-maker Allergan for $66 billion was
big news in November, and as Burrill Media
recapped that month of activity, it noted an
“increasingly competitive environment for
sought-after assets” is pushing prices higher.
The acquisition announcement topped
what Burrill Media called “another big
month for life-sciences M&A activity in
what is already a record year of dealmaking,”
and the deal raised total M&A life-sciences
activity through the first 11 months of 2014
to a record $340.8 billion, up from $118.3 billion for the same period a year ago and well
beyond the previous record set in 2009 of
$189.7 billion for M&A transactions involving therapeutics, tools, diagnostics and digital
health companies.
Actavis says the combined company will
be one of the world’s top-10 drugmakers by
revenue. The deal, which seems to end efforts
by Valeant Pharmaceuticals and hedge fund
management company Pershing Square Capital Management to acquire Allergan, benefits from Actavis’ inversion last year, prior
to September 2014 rules by the U.S. Treasury
Department aimed at curtailing inversions.
“The Actavis acquisition reflects a continued
effort by drugmakers to build their pipelines
and revenue base through acquisitions and
capitalize on synergies they can identify with
potential targets,” says G. Steven Burrill, CEO
of Burrill Media. “The accelerated pace of activity this year is an acknowledgement that companies can’t generate adequate growth through
internal development of their own pipelines.”
Partnering deals also picked up speed in
November, with companies announcing
deals with a total potential value of $7.1 billion, up from $3.9 billion during November
2013. Overall, partnering during the first
11 months of November increased to $47.9
billion, up from $35 billion during the same
period a year ago. The largest of these deals
was between Pfizer and Merck under which
Pfizer will provide Merck with an $850 million upfront payment and up to a potential
P
U
B
L
I
Prosensa provides updates
for the third quarter
LEIDEN, The Netherlands—Prosensa
C
Holding N.V., a
biopharmaceutical company focusing on RNAmodulating therapeutics for rare diseases with
high unmet need, recently reported financial
results for the third quarter ending Sept. 30 and
announced various plans and next steps for followon exon skipping compounds for the treatment of
Duchenne muscular dystrophy.
“We are incredibly pleased with the substantial
progress we have accomplished during this period.
We have delivered on our promise of initiating the
re-dosing process for patients who were previously in drisapersen clinical trials with a total of
15 boys now back on treatment, and our rolling
New Drug Application submission with the U.S.
Food & Drug Administration is currently well
underway,” said Hans Schikan, CEO of Prosensa.
Revenue for the third quarter was nil, compared
with €2.4 million (about $2.9 million) in the same
period in 2013 due to a decrease in license revenue of €1.3 million (about $1.6 million) and a
companies raised a total of $1 billion. For
the first 11 months, a total of 101 IPOs have
been completed on U.S. exchanges, compared to 49 during the same period in 2013.
IPOs completed in 2014 are up an average
of 13.5 percent, with 51 of those issues trading above their initial offering price and 50
below. Companies and investor expectations
were generally in line in November, as only
three of the offerings came modestly below
the target range and one above. n
$2 billion in additional milestones to share
rights to and co-develop Merck’s experimental immunotherapy that is designed to circumvent tumors’ ability to hide themselves
from patients’ immune systems.
Record-breaking initial public offering
(IPO) activity continued in November with
a total of 11 life-sciences companies completing initial public offerings during the month
to raise $1.2 billion globally. Ten of those
IPOs occurred on U.S. exchanges where
C O
M
P A
N
decrease in collaboration revenue of €1.1 million
(about $1.3 million) due to the termination of a
research and collaboration agreement with GSK.
Catalyst announces Q3 financials
CORAL GABLES, Fla.—Catalyst Pharmaceutical Part-
ners Inc., focused on developing and commercializing therapies for people with rare debilitating
diseases, recently reported financial results for
the third quarter and nine months ended Sept. 30.
Highlights include positive top-line Phase 3 data
from Firdapse in patients with Lambert-Eaton myasthenic syndrome and initiation of a Phase 1b safety
and tolerance study for CPP-115, a novel GABA
aminotransferase (GABA-AT) inhibitor. Upcoming
milestones include top-line results from a Tourette’s
disorder Phase 1/2 investigator-sponsored study and
exploration of additional indications for Firdapse,
such as congenital myasthenic syndrome and downbeat nystagmus; and financial results include a
GAAP net loss of about $5 million, or 7 cents per
basic and diluted share, and about $12 million, or
19 cents per basic and diluted share, for the first
Y
N
E
W
S
nine months of the fiscal year. As a developmentstage biopharma, Catalyst had no revenues in either
the third quarter or the first nine months of 2014.
uniQure offers financial update
AMSTERDAM, The Netherlands—Recently,
uniQure
N.V., which deals with human gene therapy,
announced results for the third quarter of 2014. As
of Sept. 30, the company held cash and cash
equivalents of €62.8 million (about $76.4 million).
Total revenues (consisting of licensing and collaboration revenues) for the three months ended in the
third quarter were €1 million ($1.2 million), compared with €1.3 million ($1.6 million) in the same
period of 2013. For the nine months ended Sept.
30, total revenues were €3.2 million ($3.9 million),
compared to €2.1 million ($2.5 million) in the first
nine months of 2013. In other news, uniQure is
finalizing all regulatory, trial site and administrative
preparations for the initiation of its Phase 1/2
clinical trial in hemophilia B. The company expects
dosing of the first patient to be announced in early
2015 and to announce initial results in mid-2015.
FINANCE & MARKETS
For more information, visit www.DDN-News.com
JANUARY 2015 | | DDNEWS 5
Stem cell therapies gathering momentum but challenges remain
LONDON—With 104 programs in
late-stage clinical development, the
stem cell therapy space could reach
the commercialization threshold by
2017, but a number of challenges
remain, notes research and consulting firm GlobalData in a new report
it released in December.
According to the firm, complicated manufacturing processes,
untested regulatory pathways and
a demanding economic landscape
are the largest barriers to progress in
the stem cell sector, with a number
of companies finding the business
unviable.
“Most firms operating in stem
cells are undercapitalized and rely
heavily on research grants, leveraged finance and capital raised
from public offerings or venture
capital investment to fund their
research efforts and expansion,”
said Aparna Krishnan, GlobalData’s
analyst covering healthcare industry dynamics, pointing out that the
financial challenges to the industry
have been profound, intensified by
the technology’s high failure rates.
“[The] recession impacted the
flow of investments into the sector
at a crucial time in its evolution.
Many startups and small companies that form a significant part of
the industry lacked financial discipline and often over-leveraged
themselves,” Krishnan said.
Despite this, GlobalData says that
there has been increasing investment capital flowing in from venture
capital firms, reaching a maximum
of $200 million in 2012, and there
are continued signs of investment
strength through 2013 and 2014.
“With the economy stabilizing,
attention from major drug firms
such as Pfizer and Novartis is growing, as they seek to diversify their
REVA closes Intellia
announces
financing
SAN DIEGO—REVA Medical Inc. recently announced
that the financing transaction approved by the company’s shareholders at the special meeting of stockholders held in Sydney, Australia, on Oct. 31, 2014,
has been successfully completed.
Under the terms of the prospectus dated Oct. 24,
and in accordance with the convertible note deed dated
Sept. 25, REVA issued an aggregate principal amount of
$25 million in senior unsecured convertible notes and
8,750,000 options; each option allows the noteholders
to purchase one share of REVA’s common stock.
The proceeds from the financing will be used to
fund the company’s ongoing operating, clinical and
capital needs, including the clinical program for its
Fantom bioresorbable scaffold. “We are very pleased
to announce the close of this financing,” said REVA’s
chairman and CEO Bob Stockman. “The funding we
have secured will allow REVA to move forward with
our clinical plans and to take the product through to CE
mark application, which we expect will occur in 2016.”
Fantom is a bioresorbable coronary stent made from
REVA’s proprietary polymer that is designed to dissolve over time, leaving the artery free of a permanent
implant and thereby allowing the artery to return to
its natural movement or “vasomotion.” Due to this
temporary nature, bioresorbable stents are commonly
referred to as scaffolds. Fantom’s polymer properties
also enable complete x-ray visibility of the scaffold
when placed in the artery, an attribute unique to REVA
among bioresorbable scaffolds. REVA believes that this
distinct feature will offer a procedural advantage, as
x-ray visibility helps confirm proper placement of the
scaffold and is a tool interventional cardiologists routinely rely on when implanting metal stents. n
Neothetics
announces closing
of upsized IPO
SAN DIEGO—Neothetics Inc., a clinical-stage specialty
pharmaceutical company developing therapeutics for
the aesthetic market, today announced the closing of
its initial public offering of 4,650,000 shares of its
common stock at an initial public offering price of
$14 per share.
The company originally filed to raise 4,300,000
shares. Neothetics estimates net proceeds from the
offering to be approximately $60.5 million, after
deducting underwriting discounts and commissions
and estimated offering expenses. n
$15M in
funding
CAMBRIDGE, Mass.— Intellia Therapeutics, a
new company formed to develop therapeutic
products using CRISPR-Cas9 technology for
gene editing and repair, announced in November that it has closed a Series A investment
round with $15 million in financing led by Atlas
Venture and Novartis. Created by Atlas Venture
and Caribou Biosciences, together with leading scientists shaping CRISPR biology, Intellia
leverages exclusive access to what it calls “one
of the most comprehensive intellectual property
portfolios covering the therapeutic application
of this transformative technology.”
“Discovery of the CRISPR-Cas9 system has
been a significant advance toward the long-elusive
therapeutic goal of targeting and repairing specific
genetic defects,” said Dr. Nessan Bermingham,
CEO and co-founder of Intellia. “We have assembled an experienced team with a track record of
success in all phases of development, from discovery through translation, clinical testing and commercialization. Together with our key advisors, we
are focused squarely on clinical drug development
as we progress toward our first IND filing.”
“Translating the potential of the CRISPR-Cas9
technology to focused preclinical and clinical development programs at Intellia is an exciting step
forward in the evolution of our cell engineering
platform,” said Dr. Rachel Haurwitz, CEO and cofounder of Caribou Biosciences. “The management
team, advisors and investors assembled at Intellia
have an outstanding track record of developing therapeutics that will transform the lives of patients.”
Intellia’s initial therapeutic focus is ex-vivo
applications, wherein cells are removed from
the body (collected from blood or bone marrow),
modified to correct disease-causing genes and
returned to the patient for therapeutic benefit.
Near-term ex-vivo applications include blood disorders, therapeutic protein production and cancer,
focused on such approaches as CAR-T and checkpoint inhibitor regulation.
Intellia has also initiated longer-term development of in-vivo applications, administered either systemically or locally to correct genes residing within
specific cells of the body. In-vivo applications include
ophthalmic, central nervous system, muscle, liver
and anti-infective, among other disease states. n
businesses in growth segments
through licensing deals and acquisitions,” Krishnan noted. “Also,
some stem cell companies, including Bluebird bio and Capricor, have
concluded initial public offerings,
raising enough capital to continue
research and development efforts
in the process.”
Krishnan added that the opportunity provided by stem cells in
regenerative medicine, among
other areas, is clear from the current crop of stem cell companies
and their research pipelines.
“The scientific advancement of
adult stem cells and the new technology’s demonstrable clinical benefits have led to increasing patient
acceptance. As such, GlobalData
believes that stem cells are likely
to become an integral part of the
pharmaceutical industry’s R&D
process,” the analyst concluded. n
6 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
DISCOVERY
SOUTH SAN FRANCISCO, Calif.—Calithera Biosciences
Inc. and Mars Symbioscience have inked a global
license agreement that grants Calithera exclusive
worldwide rights to research, develop and commercialize Symbioscience’s portfolio of arginase
inhibitors for use in healthcare, supporting Calithera’s goal of submitting an IND for an arginase
inhibitor for cancer treatment by the end of 2015.
Calithera will in turn make an upfront payment to
Symbioscience, in addition to potential development
and commercialization milestones and royalties on
any approved products.
Susan M. Molineaux, CEO of Calithera Biosciences, said that “I am particularly excited about this
agreement, because we believe we can apply our
core expertise in tumor biology to rapidly advance
Symbioscience’s potent and selective small-molecule
arginase inhibitors into the clinic to develop a first-inclass immuno-oncology therapy for cancer patients.”
Celgene extends exclusivity
period with Agios
CAMBRIDGE, Mass.—Under a $20-million deal with
Agios Pharmaceuticals Inc., Celgene Corp. has
extended its exclusive option to drug candidates
resulting from Agios’ platform through April 2016.
The companies have been collaborating since April
2010 for the discovery, development and commercialization of disease-altering cancer therapies
stemming from Agios’ cancer metabolism research
platform. The extension marks the final year for
the discovery phase of the collaboration under the
original terms. This follows another development
in June of this year when Celgene exercised its
exclusive option to license AG-221, a drug candidate nominated during the discovery phase of the
collaboration, gaining worldwide development and
commercialization rights, though Agios continues
to conduct early clinical development activities.
IN THIS SECTION
Academic research/Competition
Making medicines..................................... 8
Autism
Blood plasma signature may be key to
early autism diagnosis.............................. 6
Getting into the genetics of autism.......... 6
Dyslipidemia/Cardiovascular
AstraZeneca explores new target
for heart disease....................................... 6
Oncology
Calithera secures license to arginase
inhibitors.................................................... 6
Celgene extends exclusivity period
with Agios................................................. 6
Oncology/Early-stage partnering
Two partners, three initiatives,
five years (EARLY from cover).................... 9
Blood plasma signature may be
key to early autism diagnosis
Test identified autistic children
with 81-percent accuracy,
according to Stemina-UC
Davis report in PLOS One
BY LORI LESKO
MADISON, Wis.—Looking to find a way to
diagnose autism in children earlier, scientists
at Stemina Biomarker Discovery and the UC
Davis MIND Institute (Medical Investigation
of Neurodevelopmental Disorders) at the
University of California, Davis (UC Davis),
conducted a study to compare the metabolomics signatures in the blood plasma of 4-to6-year-olds with autism spectrum disorder
(ASD) with those of typically developing children. The results, published in the November 2014 issue of PLOS One, indicates that an
early-stage, blood-based test identified autistic
children with 81-percent accuracy.
The researchers analyzed metabolites in
the blood, trying to establish which of the
small molecules signal autism. This method
CREDIT: STEMINA
Calithera secures license to
arginase inhibitors
“Our study provides proof of concept that the metabolism of children with autism is
significantly different from that of typically developing children. Stemina’s metabolic approach
to diagnosing autism will revolutionize diagnosis and treatment of ASD,” says Elizabeth Donley,
co-founder and CEO of Stemina (a lab of which is pictured here).
differs from other blood-based biomarker
studies in the past few years that have tried
to detect activity or expression of genes.
“We are very pleased with the result of this
CREDIT: ERIK031
BR IEFS
Lipigon has already sent scientists to AstraZeneca to begin work on the
collaboration to identify molecules that can modulate lipoprotein
lipase. Pictured here is an AstraZeneca R&D facility in Mölndal, Sweden.
AstraZeneca
explores new target
for heart disease
LONDON—AstraZeneca
has entered into a research
collaboration with a small
Swedish biotech firm to explore
the potential for a new therapeutic
target for heart disease. The
company is partnering with
Lipigon Pharmaceuticals to
PLASMA CONTINUED ON PAGE 7
Getting into the
genetics of autism
Recent Nature study identifies 107
genes tied to autism risk
BY KELSEY KAUSTINEN
NEW YORK—According to the U.S. Centers for Disease Con-
identify molecules that modulate
lipoprotein lipase (LPL), an
enzyme that plays a role in the
metabolism of cholesterol.
Lipigon, which specializes in
LPL biology, has developed
a screening platform to find
molecules that affect the enzyme.
trol, roughly 1 percent of the world’s population presents with
autism spectrum disorder (ASD), with the numbers in the
United States standing at one in 68 children. That number is
on the rise—two years ago, U.S. statistics reported one in 88
children had autism—but thankfully, scientific and genetic
knowledge of autism is increasing as well.
A recent international study involving researchers from 37
institutions is one of the latest contributors to that knowledge base. The study, which appeared in Nature, has reported
that genetic differences in the top 107 genes were found to
impact an individual’s risk of autism. This study is the largest in autism to date, with data collected and analyzed from
3,871 autism cases, 2,270 sets of mothers, fathers and affected
children and additional control samples. The scope is thanks
to the Autism Sequencing Consortium, which was originally
funded by the Beatrice and Samuel A. Seaver Foundation and
the Seaver Autism Center within the Icahn School of Medicine
at Mount Sinai.
The study looked at data on several types of rare genetic
differences in more than 14,000 DNA samples from parents,
LPL CONTINUED ON PAGE 8
AUTISM CONTINUED ON PAGE 9
Company will work with Lipigon on potential
drugs to modulate lipoprotein lipase
BY ZACK ANCHORS
first study because it demonstrates that differences in the metabolism of children with
ASD are profound enough to distinguish
DISCOVERY
For more information, visit www.DDN-News.com
CONTINUED FROM PAGE 6
them from typically developing
children,” Elizabeth Donley, Stemina co-founder and CEO, stated
in a news release. “This will allow
us to understand the individual
metabolism of children with ASD
in a way we never could before,
leading to an earlier diagnosis and
individualized treatment.”
The etiology of the vast majority of cases of ASD are unknown
and their genetics have proven to
be incredibly complex, according
to the PLOS study.
Diagnosing the disorder as early
as possible is crucial because studies have shown earlier treatment
can boost the child’s cognitive
and social skills, Donley said. The
current standard for diagnosis is a
series of behavioral tests conducted
by experts, partly because scientists
have yet to crack the code on the
biology underpinning autism.
Donley believes the key to cracking that code lies within metabolomics, rather than focusing on biology or genetics.
“Our study provides proof of concept that the metabolism of children
with autism is significantly different from that of typically developing children,” Donley tells DDNews.
“Stemina’s metabolic approach to
diagnosing autism will revolutionize diagnosis and treatment of ASD.”
Metabolomics not only provides
an important piece of the puzzle,
but it’s an opportunity to understand what is different about the
metabolism of kids with autism
and to treat the individual child in
response to their own individual
metabolism, she says.
The current average age of an
autism diagnosis in the United
States is 4.5 years, and Stemina is
researching a diagnosis as early as
age 2, paving the way for earlier
screening and diagnosis to improve
both therapy and outcome for
patients and families.
Stemina has conducted two similar studies with roughly the same
results as the PLOS paper—another
one in partnership with the UC
Davis MIND Institute and a study
with the Arkansas Children’s Hospital Research Institute. Stemina’s
own autism test is still at least three
years and one larger-scale study
away from commercialization.
“Our work in autism began with
a study that was conducted at the
University of Wisconsin (UW)
in the lab of Dr. Gabriela Cezar,”
Donley relates. “She studied neural
cells made from human embryonic
stem cells dosed with valproic acid
(VPA) as models of neurodevelopmental disruption using a metabolomics approach to discovering
biomarkers associated with neurodevelopmental disruption. “VPA is known to cause an
increase in the incidence of autism
in children exposed during gestation, and so Dr. Cezar hypothesized
that she was creating a model of
autism in the dish that might be
seen in patients,” Donley explains.
“Dr. Cezar next studied post-mortem brain tissue from the Autism
Tissue Program and discovered
some of the same pathways disrupted in the brains of children
with autism as had been seen in
neural cells in the dish.”
This was a UW study in collaboration with Stemina, which did the
metabolomics study for Cezar’s lab,
Donley says. Stemina then sought
out sources of banked blood sam-
Copyright Cisbio Bioassays. All rights reserved. All trademarks are property of Cisbio Bioassays.
PLASMA
JANUARY 2015 | | DDNEWS 7
ples to develop a diagnostic test for
autism.
The first generation of the diagnostic test will be delivered by Stemina and its partners as a laboratory-developed test, Donley says, adding, “Next generations will include
a kit that could be used in pediatric
clinics and specialty centers.”
While Stemina’s current test can
identify about four-fifths of children
with autism by analyzing 179 small
molecules, the company’s goal is
to identify more sub-signatures, of
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give more information about the
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Stemina is trying to raise $5 million for a 1,500-patient study, Donley notes, adding she wants to begin
enrolling patients next year, with
the intention of commercializing
the autism test by the end of 2017.
“We have a lead investor for our
$5-million series B round,” Donley
reports. The Nancy Lurie Marks
Family Foundation has committed
$2.3 million to fund the clinical
study. Stemina has also applied for
a $2.7-million Phase II SBIR grant
to help support the study. Stemina
plans to initially commercialize the
test by utilizing a U.S. Food and
Drug Administration (FDA) regulatory exception that allows companies to market laboratory-developed
tests that they handle in-house, thus
bypassing the typical FDA approval
process. However, Stemina intends
to eventually seek full FDA approval
of the autism test. n
EDITCONNECT: E011504
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DISCOVERY
For more information, visit www.DDN-News.com
MAKING MEDICINES
GSK names winners of 2014
Discovery Fast Track
Challenge and explains
rationale for program
BY ILENE SCHNEIDER
MIDDLESEX, U.K.—GlaxoSmithKline (GSK),
one of the world’s leading research-based
pharmaceutical and healthcare companies,
has announced the winners of its second Discovery Fast Track Challenge. The program
is designed to combine the expertise of academic researchers with that of drug discovery
scientists at GSK to accelerate the search for
new medicines.
“There are several reasons why we do this,”
says Andrew Pope, senior director of discovery partnerships with academia and leader of
platform technology and science at GSK. “We
want to build partnerships with academia by
getting to know every academic institution
and building trust. We want to ‘de-risk’ the
target; to make medicine, we need to find
a target and have the ability to drug it. We
want people to know who we are and why
we’re different. We also think it’s a great way
to build medicines.”
Launched by GSK in the United Kingdom
in late 2010, Discovery Partnerships with
Academia is a new approach to drug discovery where academic partners become core
members of drug discovery teams. GSK and
the academic partner share the challenges
and reward of innovation as GSK funds activities in the partner laboratories and provides
in-kind resources to progress a program from
idea to candidate medicine.
Since the Fast Track Challenge program
started in 2013 in North America, every project that has been a winner has had a screen
run. The winning scientists work with GSK’s
Discovery Partnerships with Academia and
Molecular Discovery Research teams to test
their hypotheses on targets and disease pathways against GSK’s extensive library of compounds. During this process, if a compound
is identified that shows activity against these
pathways or targets, the winning investigators could be offered a formal partnership
with GSK to refine these molecules and work
together on the development of a potential
new medicine.
“It’s a long process, so we’re not yet at a
point where the initial ones have turned into
“We’re doing this to create new medicines with the
sense that building partnerships on the strengths of
both academics and companies who can commercialize
their ideas is a powerful proposition. Direct word-ofmouth builds the ability to open doors and let
academics know that we’re scientists and drug hunters
who bring capabilities and resources to their projects.”
Andrew Pope, senior director of discovery partnerships
with academia at GSK
of dyslipidemia and other
conditions that mark high risk
for cardiovascular and metabolic
CONTINUED FROM PAGE 6
disorders. Statins are now widely
Stefan Nilsson, CEO of Lipigon,
used as a means of lowering “bad”
believes that using the technology
low-density lipoprotein cholesterol
in collaboration with AstraZeneca
levels in patients at high risk of
could lead to the discovery of a
heart disease. But pharmaceutical
drug that complements the use of
companies have had less success
statins in patients at high risk for
“There have been
at developing drugs that address
heart disease.
“ There have been many many attempts to other imbalances in patients’
compounds
lipid profiles, such as elevated
attempts to find compounds that find
that are able to
triglyceride levels and low HDL
are able to activate LPL, but it’s not activate LPL, but
cholesterol levels.
easily done,” Nilsson tells DDNews. it’s not easily
Previous research has shown
“What we’ve done is unique, and done,” says Stefan
that people with low levels of
now by working with AstraZeneca Nilsson, CEO of
LPL are more likely to have
we will be able to screen one- Lipigon. “What
such imbalances. No drugs have
hundredfold more compounds we’ve done is
unique, and now
been developed, however, that
than we have capacity for on our by working with
effectively and safely target the
own.”
AstraZeneca we
enzyme as a means of lowering
LPL, which is found mostly in will be able to
triglyceride levels and raising
fatty tissue and in muscles, plays screen onea central role in breaking down hundredfold more levels of HDL cholesterol. Lipigon’s
goal is to discover a prophylactic
fat into energy for immediate use compounds than
we have capacity
drug that accomplishes this.
by the body. When triglycerides for on our own.”
“The ideal outcome would be a
accumulate in the blood as small
lipid droplets after eating, they are too large drug that can treat both low HDL and high
to be absorbed by cells. LPL cleaves the fatty triglycerides,” says Nilsson.
Lipigon has identified a number of comtails from the triglycerides to produce free fatty
acids for use by the body. The surfaces of the pounds that it believes to hold the potential
fatty droplets combine to form the components for such a drug and has examined these comof high-density lipoprotein (HDL), sometimes pounds in academic studies.
“We’ve shown these compounds to be quite
referred to as “good” cholesterol.
A drug that targets LPL has the potential powerful, and we got good data from in-vivo
to offer a new approach to the treatment models,” says Nilsson. “This created interest
LPL
partnerships,” Pope notes. “We expect at least
two partnerships out of eight winners last
year. Out of the targets selected in 2013, we
have been finding compounds that can provide new insights even if the project doesn’t
move forward into a drug discovery program.
Compelling targets may not be realistic, but
the program helps academics to know that
and move on to other projects. It’s a great
way to maximize resources for translational
research.”
In 2014, 14 winning proposals were selected from 428 entries in 26 countries across
North America and Europe. These proposals
covered a wide range of approaches and disease areas, from searching for new antibiotics
or antivirals to discovering new treatments
for cardiovascular and kidney diseases.
As Pope explains, the starting point of the
process is a website where people submit a
non-confidential proposal. From the outset,
GSK makes it clear that it is trying to facilitate the “legalese” involved in intellectual
property issues by setting forth an agreement that is “simple and that sets the stage
for a potential partnership,” he said. External
experts review and score the proposals, internal roundtables analyze them and 20 finalists
are chosen. At that point, GSK asks the institution for a confidentiality agreement and
assigns a mentor from GSK to the project.
“Then there are face-to-face meetings
with internal experts who serve as a judging
panel and provide feedback,” Pope continues. “This has been described as an enjoyable
and useful process even for non-winners.
Finally, there is the selection process with
a very high bar.”
Because there are more than 100 academic
drug discovery centers in the United States
GlaxoSmithKline expects at least two
partnerships to arise out of the eight winners
of the 2013 Fast Track Challenge. The most
recent challenge yielded 14 winning proposals.
alone, Pope thought that “ideas would be
more or less ready to go.” GSK learned that
some had not moved forward in terms of
high-throughout screening or other areas
of practical development. “There’s always
a compelling story and an able academic to
move the process forward, and that’s why we
take on the work of making it happen.”
Pope concludes: “We’re doing this to create new medicines with the sense that building partnerships on the strengths of both
academics and companies who can commercialize their ideas is a powerful proposition. Direct word-of-mouth builds the ability
to open doors and let academics know that
we’re scientists and drug hunters who bring
capabilities and resources to their projects.” n
EDITCONNECT: E011507
“This is an exciting opportunity where a small Swedish
biotech company with an innovative approach
complements AstraZeneca’s research in cardiovascular
and metabolic diseases. Lipigon is internationally
recognized for their scientific knowledge and
technological know-how in a challenging area.”
Marcus Schindler, vice-president of AstraZeneca’s
Innovative Medicines unit
in our company from pharmaceuticals and
led to our partnership with AstraZeneca.”
Nilsson tells DDNews that a drug that targets
LPL could be used in some patients to complement statins. “This would be a perfect complement for use with high-risk patients who are
already on statin treatment,” he says. “This is
important because statins in combination with
other conventional treatments only prevent
about 25 percent of heart attacks.”
The terms of the agreement call for the
companies to use Lipigon’s screening platform to develop a high-throughput assay that
identifies molecules that promote stabilization of LPL. “We’ve screened 17,500 compounds on our own, so the ultimate goal is
to screen AstraZeneca’s compound library
that includes a couple million,” says Nilsson.
“That will give us a much greater chance of
finding compounds that are even more efficient and more drugable than what we have
right now.” Lipigon, which has already sent
scientists to AstraZeneca to begin work, is
receiving upfront payment in addition to
milestone payments from the pharmaceutical company.
“This is an exciting opportunity where
a small Swedish biotech company with
an innovative approach complements
AstraZeneca’s research in cardiovascular and
metabolic diseases,” says Marcus Schindler,
vice president of AstraZeneca’s Innovative
Medicines unit. “Lipigon is internationally
recognized for their scientific knowledge and
technological know-how in a challenging area.”
Throughout its partnership with
AstraZeneca, Lipigon will continue to
explore the potential of compounds affecting
LPL that it has already discovered on its own.
“We want to work on the compounds we’ve
found on our own so that we have all options
available in terms of capital investment,”
Nilsson tells DDNews. n
EDITCONNECT: E011505
For more information, visit www.DDN-News.com
AUTISM
CONTINUED FROM PAGE 6
affected children and unrelated individuals,
which resulted in a multitude of new genes
linked with ASD. Where until recently
only nine genes have been closely linked to
autism risk, this study nearly quadrupled
the number of genes definitively associated
with autism to 33. More than 70 additional
likely ASD genes were also identified, with
each one mutated in more than 5 percent
of autistic individuals. The researchers used
DNA sequencing techniques that can determine the order of the genetic “letters” in
DNA to reveal variations, with whole-exome
sequencing utilized as well.
“The steps we added to our analysis over
past studies provide the most complete
theoretical picture to date of how many
genetic changes pile up to affect the brains
of children with autism. Beyond autism, we
think this work will yield insights into what
makes us social beings,” said Dr. Joseph D.
Buxbaum, professor of psychiatry, neuroscience and genetics and genomic sciences at
the Icahn School of Medicine at Mount Sinai
and director of the Seaver Autism Center.
This study found that three pathways
required for healthy development are linked
to increased autism risk when mutations are
present. One of the key discoveries for this
study was the association discovered between
autism risk and mutations in genes responsible for controlling chromatin remodeling,
which plays a key role in DNA processes.
“What was novel was that we saw for the
first time, on large scale, that chromatin
remodeling is a major area for autism risk.
DISCOVERY
Synaptic formation and turnover happens
over our lifetime, but chromatin remodeling is especially important in development,”
says Buxbaum, who, along with Dr. Mark J.
Daly, co-director of the Program in Medical
and Population Genetics at the Broad Institute of MIT and Harvard, is senior author
of the study.
Along those lines, one of the groups of
genes this study has linked to autism codes
for an enzyme that regulates histones by
attaching or removing methyl groups to one
of their building blocks, thereby influencing when certain genes are turned on or off.
This aligns with the theory that these mechanisms are altered in autism, with the result
that developing brain cells might not mature,
divide or migrate in the same way.
Other variations were seen in genes that
govern synapses, as well as in another group
of genes that regulate basic steps that turn
genes into proteins.
While past studies regarding genetic
autism risk have focused only on de-novo
loss-of-function mutations, this Nature study
examined inherited and de-novo loss-of-function mutations, as well as de-novo missense
mutations, in which a protein is present but
does not work properly.
“Until now, nobody’s looked formally at
missense mutations. So we’re able to show
very clearly that missense mutations, the
more deleterious ones, are a major part of
risk and actually can be equally deleterious
as the loss-of-function mutations,” Buxbaum
tells DDNews.
“While we have very strong findings in
these genetic analyses, newfound genetic
discoveries must next be moved into molecu-
The scope of a recent study on autism genetics is thanks to the Autism Sequencing
Consortium, originally funded by the Beatrice and Samuel A. Seaver Foundation and the Seaver
Autism Center within the Icahn School of Medicine at Mount Sinai. Pictured here is Mount
Sinai Hospital, which is affiliated with Icahn.
lar, cell and animal studies to realize future
benefits for families,” he adds. “A study like
this creates an industry for years to come,
with labs worldwide checking the brain
changes linked to each new genetic finding
and searching for drugs to counter them.”
Another recent Nature study shed further
light on autism risk and the contribution
genetic mutations play in that sphere. The
study, “The contribution of de novo coding
mutations to autism spectrum disorder,”
was co-led by investigators from Cold Spring
Harbor Laboratory, Yale University, the Uni-
EARLY
CONTINUED FROM PAGE 1
collaboration partner to the pharma and biotech industry as well as academia.”
This collaboration will entail a minimum
guaranteed commitment from Sanofi to Evotec of €250 million (approximately $309.5
million) over the next five years, including
an upfront cash payment to be defined in the
agreement. The initiative will also include a
co-development agreement with associated
upfront, development, regulatory and sales
milestones, in addition to royalties that will
benefit both parties. This deal is expected to
be signed in the first half of 2015, subject to
finalization of the definitive agreements and
completion of the appropriate social process.
A key part of the deal involves Evotec taking over Sanofi’s Toulouse-based research
and development operations—in 2012, those
operations were threatened with closure to
cut costs, though pressure from the French
government and trade unions prevented such
closure from taking place.
“Open innovation is a key driver of Sanofi’s
strategy. We believe Evotec will be an ideal
partner, a company that fits our quality
expectations and our strategic vision. Our
collaboration will secure the future for our
employees in Toulouse and importantly
accelerate our pipeline productivity,” Dr.
Elias Zerhouni, president of global R&D for
Sanofi, commented in a statement.
Within the three strategic initiatives, one
will consist of pipeline-building, in which
Sanofi and Evotec will collaborate on selected preclinical development projects with a
focus on oncology and potential Cure X/Target X initiatives. Typically, that will feature
The collaboration between Sanofi (pictured here) and Evotec will entail a minimum guaranteed
commitment from Sanofi to Evotec of more than $309 million over the next five years.
Evotec accelerating projects to the point of
clinical development candidates, at which
point Sanofi may take over development
and commercialization. Evotec will license
a portfolio of projects from Sanofi, including
five preclinical projects in oncology that the
companies will jointly progress to the IND
stage before potential partnering.
Additionally, Evotec will continue expanding its Cure X/Target X business model, an
initiative that Sanofi will fund through a commitment to Evotec’s scouting strategy over the
course of the agreements. Sanofi could also
provide support for individual projects that
progress through this program. In addition,
Evotec will expand its capabilities by acquiring Sanofi’s drug discovery operations in Toulouse, a small-molecule discovery site with
more than 200 scientists. Evotec’s expanded
JANUARY 2015 | | DDNEWS 9
capabilities will cover the early-stage discovery and preclinical process from screening
to medicinal chemistry. In conjunction with
these initiatives, the companies will be combining their small-molecule libraries to make
them available for screening to Evotec’s partners. Sanofi’s library, established on its Toulouse site, has over one million compounds,
greatly boosting Evotec’s library of more than
400,000 compounds. Evotec will screen the
libraries against collaborators’ and partners’
targets under pre-agreed upon terms, from
which Sanofi will receive a contribution if a
product is developed from a library hit. “We
are very proud that Sanofi has chosen Evotec
for this significant alliance,” Dr. Werner Lanthaler, CEO of Evotec, said in a press release.
“This collaboration is a major milestone in the
drug discovery space and accelerates Evotec’s
versity of Washington and the University of
California, San Francisco.
The researchers report that based on their
work, at least 30 percent of all autism cases are
the result of de-novo mutations—and that is
likely a conservative estimate. There are three
major contributors to that number: missense
mutations, likely gene-disrupting (LGD)
mutations and large-scale copy number variations. Missense mutations were noted as the
cause of 12 percent of autism cases, and LGD
mutations as the cause of 9 percent. n
EDITCONNECT: E011506
strategy to become the leading drug discovery
partner to the pharma and biotech industry
as well as academia. We will warmly welcome
the Sanofi employees to the Evotec Group and
look forward to working with them.”
In other early-stage news for Evotec,
announced a couple weeks after the Sanofi
deal, the company noted it achieved multiple
milestones in ongoing alliances with strategic research partners. The milestones were
reached in its multi-target collaboration with
Bayer HealthCare in endometriosis and in its
partnership with Janssen Pharmaceuticals
Inc. for the EVT100 series for the treatment of
central nervous system (CNS) diseases. These
milestones trigger revenues of approximately
€8 million (about $9.7 million), which Evotec
says will be recognized in fiscal 2014.
In its collaboration with Bayer, Evotec
reached important milestones for the transition of certain molecules into preclinical
development for the treatment of endometriosis. These milestones were achieved under
the agreement between Evotec and Bayer
signed in October 2012. The goal of this collaboration is to identify three clinical candidates within the five-year alliance. According
to Evotec, “Both parties contribute innovative drug targets and high-quality technology
infrastructures and share the responsibility
for early research and preclinical characterization of potential clinical candidates in the
disease area of endometriosis.”
In its collaboration with Janssen on a
NR2B subtype selective NMDA-antagonist
portfolio for development against CNS diseases, Evotec said merely that it had “reached
an important validation milestone for a new
compound.” n
EDITCONNECT: E011503
10 DDNEWS | | JANUARY 2015
EDITORIAL
For more information, visit www.DDN-News.com
Making a big deal of mergers
O
he noted, “The accelerated pace of activity this
NE OF THE CHALLENGES of being year is an acknowledgement that companies
a monthly news-based magazine can’t generate adequate growth through internal
is that, sometimes, things fall development of their own pipelines” and that
through the cracks. Well, not they are looking not just for potentially valuable
exactly; sometimes they just pipeline-boosters, but also for companies
don’t get into the niche you might have wanted. that are synergistic with their own goals and
philosophies.
Back in mid-November came the
Looking at the Actavis-Allergan
news that Actavis had announced
deal, Zacks Investment Research
a definitive agreement by which it
wrote, “The addition of several
would acquire Allergan in a deal
blockbuster therapeutic franchises
worth approximately $66 billion,
will boost Actavis’ North American
serving as the rescuer for Allergan,
Specialty Brands business
which had been fending off an
significantly … the combined
unsolicited—and unwanted—offer
company will have three blockbuster
from Valeant Pharmaceuticals.
f r a n c h i s e s ( o p h t h a l m o l o g y,
It was too late to shoehorn that
neurosciences/CNS and medical
story into the December print issue, Jeffrey Bouley,
DDNews Chief Editor
aesthetics/dermatology/plastic
which was well underway, and by
the time this January issue was being planned, surgery), each with annual revenues of more
the news didn’t seem fresh enough to run on than $3 billion. Meanwhile, the specialty product
the cover or in one of our news sections. Still, franchises (gastroenterology, cardiovascular,
$66 billion is a mighty large number, and the women’s health, urology and infectious disease)
story bears mentioning in some form in print, will have combined revenues of about $4 billion.”
Still, it remains to be seen whether that $66
so why not here? (We did cover the story on our
website, and you can read it by searching for the billion will pay off handsomely in the long run.
Editconnect number, which is E11201401.) In And while other deals weren’t so big, they also
fact, this “Editor’s Focus” isn’t the only place it’s raise concerns that—at least in some cases—
mentioned. In our Finance & Markets section too much might be getting spent on the as-yetthis issue, on page 4, G. Steven Burrill, CEO of unrealized promise of payoffs.
For example, in an M&A story that appears
Burrill Media, notes that not only did the deal
help push 2014 merger and acquisition (M&A) on the cover of this issue, Merck & Co. decided
activity to clearly record levels, but also that to strike a deal to buy Cubist Pharmaceuticals
it signals a more competitive environment in Inc. in a transaction valued at around $9.5
which a lot of companies with money to spend billion ($8.4 billion upfront and assumption
or financing they can access are trying to gobble of more than a billion in debt). Both investors
up valuable assets that they didn’t develop. As and analysts have expressed concern that Merck
BY JEFFREY BOULEY
may have paid too much, perhaps by as much
as $3 billion. That may not seem like much in
comparison to the Actavis/Allergan deal, but it
matters. This is an industry where no therapeutic
or diagnostic is guaranteed to win approval and
make it to market, and the costs are high.
As Forbes noted in an August 2013 article,
66 of 98 companies studied launched just one
drug over the previous decade, and that was at
a median cost per drug of $350 million—more
startling was that for companies that approve
more drugs, the costs rose drastically until it hit
$5.5 billion for companies that have brought to
market between eight and 13 medicines over
a decade. In more recent data in November
2014, the Tufts Center for the Study of Drug
Development estimated that drug makers can
expect to spend more than $2.5 billion over a
decade before winning approval to sell a new
prescription medicine.
The rewards are high, both for blockbuster
drugs that serve large patient populations and
very expensive niche drugs for rare diseases. But
the costs are getting higher, too, and only time
will tell if that is money well spent. n
JE SUIS CHARLIE...
As this issue went to press, French satirical magazine
“Charlie Hebdo” had just a couple days before been the
victim of a deadly attack by extremists who apparently
wished to make a violent statement about the publication’s
use of free speech. As a journalistic vehicle ourselves, we
stand in unity with others who put the pen and keyboard
to use around the world, whether politically, satirically,
informationally or otherwise. Our hearts go out to the
victims, their loved ones and their associates.
Out of Order: Substance over volume
W
BY RANDALL C WILLIS
HEN YOU MEET SOMEONE who
does not speak your language,
there is a cliché response of
talking louder to make yourself
understood. There is something within many
of us that says if we simply pump up the volume,
we can overcome the disconnect.
A couple of months ago, Tufts University
released their latest estimates for the average
cost of developing a new drug: $2.6 billion
(I’ve seen estimates up to $5 billion). Eleven
years ago, the same group calculated the costs
at $0.8 billion.
Now, every time these estimates arise, the
hand-wringing begins over how the costs were
calculated, which factors make sense and which
are over-reaching. What no one seems to argue,
however, is that drugs are less expensive to
develop today than they were a decade ago.
So what has this to do with speaking louder?
The same period has seen amazing
technological achievements designed to
facilitate and accelerate drug discovery and
development.
Combinatorial chemistry was heralded as
a way to expand compound libraries from
hundreds to hundreds of thousands. Highthroughput and high-content screening, as well
as miniaturization and automation, were lauded
as ways to screen all of these compounds faster
under the paradigm of “fail early, fail often.”
And given the masses of data these technologies
would churn out, the informatics revolution was
supposed to convert data into knowledge and
knowledge into healthcare.
And yet, for all of these improvements in efficiency with throughput hasn’t improved
throughput, I question whether we have seen our precision at the cost of our accuracy. If you
ask the wrong question, all of the
much improvement in the number
throughput in the world won’t get
or quality of drugs being produced.
you closer to the right answer.
We certainly haven’t made them less
In researching the DDNews
expensive.
Special Reports over the last couple
Please understand, I don’t place
of years, I have spoken at length
any fault in the technologies. These
to several pharma and biotech
are truly marvels of engineering.
specialists about this topic, and
Rather, I question the applications
many feel that the industrialization
and expectations of the technologies.
of drug discovery and development
Almost two years ago, GSK
has underwhelmed if not outright
CEO Andrew Witty told a London Randall C Willis
failed. Several have suggested it
healthcare conference: “It’s entirely
achievable that we can improve the efficiency is time to step back and learn to ask better
of the industry and pass that forward in terms questions of our technologies.
But getting back to the costs issue.
of reduced prices.”
I know many will rightly point out that the
The pivotal question here, I believe, is how
largest expense comes from clinical trials. To
one defines efficiency.
I wonder how many people simply felt address this challenge, new technologies and
economies of scale would improve discovery, methodologies are being developed to get the
much as mass production made Henry Ford a most useful information out of the smallest
rich man. But drugs are not cars, and where patient populations.
Here again, however, no one segment of the
throughput and scale make sense when you
have a fully characterized end product, they have drug development process stands in isolation,
and I think back to the compounds reaching the
their limitations during exploration.
When I was a protein biochemist in an NMR clinic and question the expense of incremental
structural biology lab, I spent some time trying improvements.
Oncolytics CEO Brad Thompson discussed
to wrap my head around two concepts: precision
and accuracy. A 3-Å protein structure is very the challenge in Cancer in the Clinic (June 2014
precise, but if the structure isn’t truly reflective DDNews).
“If you could double [overall survival], you
of what happens in nature, it is meaningless. A
30-Å protein structure is much less precise, but could show that in a couple of hundred patients.
if it is more accurate, more in tune with nature, If you want to do a 10-percent improvement,
you’re talking thousands of patients to do it to
then it is likely more useful.
By comparison, I wonder if our zeal to equate
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EDITORIAL
JANUARY 2015 | | DDNEWS 11
COMMENTARY: Solutions to the drug development
cycle and antibiotic resistance problems
drug development. Target-based research,
with its large investments and reliance on
HE CELL-BASED ASSAY arena different ‘omics, has shown limited output,
has become highly prevalent with the number of new chemical entities
due to the serious, major and significantly decreased.
Calorimetry, and especially IMC, has
mounting medical challenges
some unique properties that
facing healthcare
link high-throughput screening
internationally—both financial
and primary screens to in-vivo
in the field of drug development
results. IMC, being a continuous
and curative in the arena of
and nondestructive technology,
antibiotic resistance. Calorimetry
allows the study of disease
is a mature technique, available
models from 2D to 3D to tissue,
in a modern 3D holistic format,
paving the way for cost efficiency
that provides the answers to a
and better predictability in drug
number of some of these critical
development.
challenges.
Magnus Jansson of
Novel cell-based assays
Measurement of the total SymCel Sverige AB
with better predictive power
metabolic response of a biological
system is a true time- and cost-efficient link target binding potential to the true
complement to existing assays and a highly phenotype response of the organism, the
human. Calorimetry is unique in that it is
valuable proposition.
completely independent of cell morphology
Power and metabolic activity
and media composition.
Most cell-based assays are limited to
All living cells produce heat through chemical
and physical processes. By monitoring specific growth media or 2D cell cultures
heat flow over time (J/s or W), significant Calorimetry assays can be run using
information is obtained regarding biological conventional 2D cell growth and various
systems. Calorimetry-based assays represent types of 3D cell models on matrices or
true measurements of the cellular phenotypic synthetic tissue models, as well as tissue
response. Any changes in nutrient status, the samples directly from donors. IMC increases
environment or external stimuli are reflected the value of the assays, as it is not necessary
in the metabolic status of the living cell, which to know the timeframe for a cellular event.
is directly monitored by the calorimetric Additionally, postexperimental analysis of
assay. Isothermal microcalorimetry (IMC) protein and RNA levels can be performed.
These properties make IMC extremely
is specific due to the fact that samples are
kept at a constant temperature during the relevant for studying disease models from
2D to 3D to tissue. Furthermore, it is also
course of experiments.
possible to apply whole-body calorimetry to
Calorimetry: A specific
correlate between in-vitro models and in-vivo
footprint of cellular events
results, especially in metabolic research,
IMC provides the potential for rapid where energy expenditure is key.
identification and quantification as it
measures the total metabolic status and IMC: An open platform that
response of a cellular system. This makes IMC changes scientific development
a true phenotype assay with the benefit that Open platform solutions face strong demand,
very little information is required about the especially at the higher end of the assay
system to be studied. Faster results in drug market. Expensive lab equipment, usable
discovery and cell research are generated due for more than one assay type, presents a
to the fact that there is no need to know the better and more cost-effective use of scarce
pathways or receptors involved in a process. resources than existing, highly specialized,
Consequently, novel systems can be studied locked-in equipment. IMC is a very open
directly, leading to quicker results in drug platform and its sole limitation is the
discovery and cell research.
creativity of the scientist, not the technology.
IMC is a continuous measurement and The development of novel antibiotic
the power over time curve is comparable to substances is a prime example, in which IMC
a specific footprint for the cellular events can easily be adapted for novel compound
involved. For example, the power curves are testing. The same IMC can then be utilized to
different for necrosis and apoptosis, and the evaluate cellular toxicity for lead compounds
effects of different compounds can thus be on mammalian cell cultures.
classified based on the “kinetic” profile of a
specific compound. For prokaryotes, there Applications: Metabolic drug discovery
are different growth patterns for different Energy expenditure assays are used in
species and for different nutritional status. metabolic disease drug discovery, but they
This can potentially be used for rapid are not limited to this field. It is clear that
identification and quantification.
IMC has direct advantages for metabolic
drug development since the kinetic profiling
3D potential: Holistic approaches and
of the cellular metabolism makes it possible
a new dawn for drug discovery
to distinguish between different cellular
Genotype-based research, complemented events. IMC is also well suited for finding
with phenotype results, is an important and distinguishing between apoptotic and
research direction in drug discovery that is necrotic mechanisms and grouping antibody
replacing the previous focus on target-based behavior-based killing kinetics and efficacy.
BY MAGNUS JANSSON, CHIEF SCIENTIFIC
T
OFFICER OF SYMCEL SVERIGE AB
Antibiotic resistance
The medical/pharmaceutical world is facing
an enormous challenge to rapidly develop
novel antibiotic classes. IMC can easily be
used to quantify the effects of novel antibiotics
on bacterial viability and growth. Closedampule IMC captures basic pharmacologic
information, e.g., minimum inhibitory
concentration of an antibiotic needed to
stop growth of a given organism. Also, it
can simultaneously provide dynamic growth
parameters—lag time and maximum growth
rate. IMC provides a rapid, cost-efficient
development scheme for novel antibiotics.
Antiparasite drugs
With IMC, it is possible to use whole intact
organisms, thereby providing a novel tool for
antiparasite drug development. Parasites of
the Helmint type easily fit in modern, highthroughput IMC, and the drug efficacy can
be tested on the whole organism. Manual
input is minimal compared to the current
microscopy assays used.
Bacteriological disease control
IMC can be used as a diagnostics tool in the
field of bacteriological disease control. This
is because IMC has very high sensitivity to
rapidly detect slow-growing organisms, such
as in tuberculosis, generating considerable
time and cost savings. In the future, when
personalized medicine has matured, IMC
will potentially be used in prescreening for the
treatment of diseases like leukemia. The direct
drug effect can be studied in individual patient
material prior to treatment with minimal
lag, increasing the likelihood of a successful
treatment scheme.
Ease of working with IMC
Novel technological developments now
make IMC more adaptable to cell biology
research. The combined benefits of increased
throughput; presterilized, cell growthcompatible disposables; higher sensitivity;
and decreased use of cells and chemicals,
combined with easier data interpretation,
are too important to disregard. Together with
outstanding cost efficiency, this positions
IMC as a state-of-the-art technology and
increases the IMC-based assay usage in cell
biology research.
Conclusion
Isothermal microcalorimetry-based cell
assays provide multiple advantages,
especially given that all living cells produce
metabolic heat. There is a now great deal of
valuable information available in heat which
previously wasn’t given much weight due to
old perceptions and a complete lack of tools.
IMC is a label-free technology that is
sensitive, fast and low-cost, continuously
provides important time-resolved data, is
nondestructive, has few limits in morphology
other than size and is nonspecific.
Furthermore, by carefully designing and
posing the right questions in each study, IMC
is no different than any other type of assay.
In conclusion, isothermal calorimetry
complements a wide number of cell-based
assays, from manual microscopic inspection
to oxygen consumption and capacitance
measurements. The only limit to possible
application areas is creativity. Recent
advances in equipment make calorimetry
more accessible for the cell environmentalist.
The holistic approach, in which 3D cultures
and phenotype response are poised to provide
predictable models, requires novel tools.
Calorimetry should now be thought of
as label-free cell monitoring. Essentially,
calorimetry is a good complement to the
many current trends in drug discovery and
prioritized research areas. Indeed, cell-based
assays can now be performed on a versatile and
adaptable platform that provides considerably
more information with significantly less
effort. Calorimetry has arrived. n
REFERENCES
1.Manneck, T.; Braissant, O. et al. J. Clin. Microbiol.
2011 Apr, 49(4), 1217-25; doi: 10.1128/JCM.02382-10;
Epub 2011 Jan 26.
2.Kirchhofer, C.; Vargas, M. Acta Trop. 2011 Apr,
118(1), 56-62; doi: 10.1016/j.actatropica.2011.02.003;
Epub 2011 Feb 21.
3.Global tuberculosis report 2013. WHO Library
Cataloguing-in-Publication Data: 1. Tuberculosis—
epidemiology. 2. Tuberculosis, Pulmonary—prevention
and control. 3. Tuberculosis—economics. 4.
Tuberculosis, Multidrug-Resistant. 5. Annual reports. I.
World Health Organization. ISBN 978 92 4 156465 6.
4.Howell, M.; Wirz, D. et al. J. Clin. Microbiol.
2012 Jan, 50(1):16-20; doi: 10.1128/JCM.05556-11;
Epub 2011 Nov 16.
5.http://en.wikipedia.org/wiki/Isothermal_
microcalorimetry.
6.Braissant, O.; Wirz, D. et al. Sensors (Basel) 2010,
10(10), 9369-83; doi: 10.3390/s101009369; Epub
2010 Oct 18.
ORDER
CONTINUED FROM PAGE 10
the statistical level that everybody
would prefer to see. How do you run
a study like that?”
That is a huge difference in financial
expenditure that begs the question is
an efficacy improvement of just 10
percent of value.
From an individual patient
perspective, assuredly. From a
pharmacoeconomic perspective,
maybe not, and particularly with
the growing prevalence of high-cost
targeted biologics. Maybe we need to
aim for bigger improvements before
moving candidates forward, which
happens long before the clinic.
Again, I’m not placing blame.
The history of any industry is filled
with experimentation in different
methodologies and technologies.
Everyone involved had the best of
intentions.
But after a couple of decades of
middling results, perhaps it is time to
question how and when many of these
advancements are applied. Simply
yelling at a higher volume doesn’t
seem to be enough. n
The opinions expressed in guest commentaries do not necessarily represent those of DDNews and/or its owners, editors or other staff.
12 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
RESEARCH & DEVELOPMENT
Codexis demonstrates
proof of concept for PKU therapy
REDWOOD CITY, Calif.—Codexis Inc. has developed
a novel enzyme therapeutic product candidate for
the potential treatment of phenylketonuria (PKU)
via oral administration. In PKU, the enzyme that
converts phenylalanine into tyrosine is deficient,
causing phenylalanine to accumulate in high levels
in the brain, which leads to severe neurological
problems. Studies conducted in an animal model of
PKU demonstrated proof of concept for the product
candidate, which, when introduced into the stomach of animal models, resulted in decreased blood
phenylalanine levels. Codexis has filed patent
applications covering the composition of matter
for its enzymes and their use in treating PKU, and
is seeking partners to advance the development
of the PKU program. Preclinical studies for the
enzyme therapeutic candidate are expected to
begin next year.
Horizon inks supply and
licensing deal with Adarza
CAMBRIDGE, U.K & ST. LOUIS—An exclusive license
and supply agreement was announced between
Horizon Discovery Group plc and Adarza BioSystems Inc. that grants Horizon the exclusive right to
supply services on Adarza’s multiplex immunoassay
technology, Arrayed Imaging Reflectometry. Under
this agreement, Horizon has exclusive rights to offer
research services using Adarza’s platform, and next
year, Horizon will launch a portfolio of products that
can detect between 100 and 400 analytes and will
offer custom assay development on the platform.
“We are delighted to be working with one of
the world’s fastest-growing life-science companies
dedicated to driving forward the fields of gene editing and translational genomics. The agreement with
Horizon validates Adarza’s disruptive technology
platform and allows us to leverage Horizon’s worldclass sales and marketing network to bring the technology to market sooner and much more broadly
than we could alone,” said Dr. Preston Keller,
Adarza’s vice president of business development.
IN THIS SECTION
Efficacy/Toxicity
Preferred tox partner............................... 12
HIV/AIDS
Nanofiber vs. HIV..................................... 14
Immunoassay technology
Horizon inks supply and licensing
deal with Adarza..................................... 12
Microbiome
Focus on the microbiome........................ 12
Oncology/Nanomedicines
Joint R&D on Accurins............................ 12
Phenylketonuria
Codexis demonstrates proof
of concept for PKU therapy..................... 12
PREFERRED TOX PARTNER
MicroMatrices enters
partnership agreement for
use of ACD’s RNAscope
technology
BY ILENE SCHNEIDER
DUNDEE, U.K.—MicroMatrices, a service
provider specializing in high-resolution cell
type-specific analysis to characterize toxicological responses in different cell types in
tissue, has entered a preferred partnership
agreement with Advanced Cell Diagnostics
Inc. (ACD), a leader in the field of molecular
pathology and developer of cell- and tissuebased analysis tools.
MicroMatrices solves molecular toxicological problems using
visualization and localization
technologies, adding resolving
power to standard methodologies. The company specializes
in immunohistochemistry staining and
has recently become expert in the use of
ACD’s RNAscope technology to detect RNA
based biomarkers in situ. According to the
companies, this has resulted in expertise in
combined protein/RNA co-detection and co-
localization to offer clients an exceptional
target visualization capacity that can guide
and/or corroborate mechanistic and mode
of action studies. In recognition of MicroMatrices’ extensive experience in applying
RNAscope in preclinical toxicology investigations for safety and efficacy, ACD has begun a
preferred partnership program for the provision and/or development of preclinical applications of RNAscope Technology.
ACD and MicroMatrices first met in
2012 at the Society for Toxicology (SOT)
meeting in San Francisco, when both companies were within their first one or two
years of operation. When Simon
Plummer, managing director of
MicroMatrices, visited the ACD
exhibition at the SOT ToxExpo,
he “quickly recognized the power
of ACD’s RNAscope technology
and saw how it could significantly
enhance existing visualization technologies
used in preclinical toxicology investigations.”
As Plummer explains, “Over the past two
years, this early assessment has been proven to
be correct. RNAscope technology has played
a central role in the services MicroMatrices
TOOLS &
TECHNOLOGY
CREDIT: BIND THERAPEUTICS
BRIEFS
Accurins represent the next stage in the evolution of targeted
therapies and nanomedicine, according to BIND Therapeutics. Accurin
nanoparticles are designed to encapsulate cancer-killing drugs in a
biodegradable polymer shell and bring them specifically to cancer
cells, while avoiding healthy ones.
BY LORI LESKO
CAMBRIDGE, Mass.— Biotech
company BIND Therapeutics Inc.
has entered into a joint research
offers to its clients in the chemical/pharmaceutical industries and has helped to guide
and/or corroborate many significant mechaTOX CONTINUED ON PAGE 13
Focus on the
microbiome
MIT partnership with
Massachusetts General Hospital,
other institutions to foster regional
ecosystem for rapidly evolving field
BY LLOYD DUNLAP
CAMBRIDGE, Mass.—Although perhaps not top of mind for
and development agreement
with New Jersey-based pharma
giant Merck & Co. to discover
and develop novel nanomedicines for oncology and expand
the company’s pipeline with at
least two new clinical candidates.
The financial terms are not
being disclosed, but BIND is
expected to pay for research up
through early-stage human testing, and if Merck takes over, it
most researchers, more than 90 percent of the genes in our
bodies do not come from our own cells. Instead, the vast
majority of this genetic material is found within the trillions
of microorganisms that call our bodies home. Collectively
known as the microbiome, these communities of bacteria and
other microbes play a significant role in the functioning of the
digestive tract, immune system, skin and other body systems.
In recent years, the microbiome has attracted increasing
attention for its role in health and disease. Recently, the Massachusetts Institute of Technology (MIT) and Massachusetts
General Hospital (MGH) announced the launch of the Center
for Microbiome Informatics and Therapeutics, a new interdisciplinary center dedicated to advancing the understanding of
the microbiome’s role in human biology and harnessing this
knowledge to develop treatments for related illnesses.
With an expendable $25-million fund to support research
and operations for the first five years, the center will fuel
ACCURIN CONTINUED ON PAGE 14
MICRO CONTINUED ON PAGE 15
Joint R&D on Accurins
BIND and Merck
collaborate on
developing
nanomedicines for
oncology, pipeline
expansion
“Essentially MicroMatrices, through its
partner Aquila Histoplex, will be able to
provide preclinical applications of RNAscope
to clients seeking to assess mechanistic and
mode of action studies, as well as aid target
validation,” says Barry Lynch, regional sales
director at Advanced Cell Diagnostics.
For more information, visit www.DDN-News.com
TOX
CONTINUED FROM PAGE 12
nistic and mode-of-action studies,
as well as aid target validation.”
He adds, “The power and versatility of RNAscope has been an
invaluable tool to enable us to
solve mode of action/efficacy/toxicity challenges for our clients in the
pharmaceutical, agrochemical and
chemical industries. We are delighted to be partnering with ACD to
promote the wider application of
RNAscope technology in preclinical safety/drug development problem solving for our collaborators.”
The preferred partnership between
the two companies has been established as a practical and reciprocal
marketing strategy that enables ACD
to add value to its product portfolio by
linking with MicroMatrices, a company that has extensive experience
in applying RNAscope within preclinical toxicological investigations.
Likewise, the partnership with ACD
will raise awareness within a wider
customer base of the powerful, inno-
“The power and
versatility of
RNAscope has been an
invaluable tool to
enable us to solve
mode of action/
efficacy/toxicity
challenges for our
clients in the
pharmaceutical,
agrochemical and
chemical industries.”
Simon Plummer,
managing director of
MicroMatrices
vative investigative approaches to
safety/efficacy questions MicroMatrices can offer, according to Plummer.
ACD’s RNAscope assays represent a major technological advance
for in-situ RNA detection. For the
first time, the company says, robust
single RNA molecule detection is
available for formalin-fixed, paraffinembedded tissue, offering quantitative molecular detection with morphological context in a single assay.
Since their commercialization three
years ago, these assays have been
adopted across the globe by major
pharma biotech companies and leading research institutions for drug
discovery, translational research
and the development of clinical and
companion diagnostic tests.
According to Barry Lynch, regional sales director at ACD, “Essentially
MicroMatrices, through its partner
Aquila Histoplex, will be able to
provide preclinical applications
of RNAscope to clients seeking to
assess mechanistic and mode of
action studies, as well as aid target
validation.”
RESEARCH & DEVELOPMENT
JANUARY 2015 | | DDNEWS 13
“ACD has established high-quality performance standards through RNAscope products and
services, and MicroMatrices is known for quality, service and expertise in the drug development
community. As ACD’s install base is growing very rapidly in Europe, MicroMatrices is an ideal
partner not only to extend our reach but also to solidify our commitment in service quality.”
Dr. Steve Chen, chief operating officer of ACD
“ACD has established high-quality performance standards through
RNAscope products and services,
and MicroMatrices is known for
quality, service and expertise in
the drug development community,” according to Dr. Steve Chen,
chief operating officer of ACD. “As
ACD’s install base is growing very
rapidly in Europe, MicroMatrices is
an ideal partner not only to extend
our reach but also to solidify our
commitment in service quality.”
Both companies say that the part-
nership is open-ended. Plummer
believes that there is commercial
potential for both companies in the
partnership: ACD should tap into
new markets as its technologies
are taken up for use in preclinical
safety applications, and MicroMa-
trices stands to benefit by virtue of
the recognition offered to its track
record/expertise in executing these
applications, which it can offer to
new clients on either a contract or
consultancy basis. n
EDITCONNECT: E011508
RESEARCH & DEVELOPMENT
14 DDNEWS | | JANUARY 2015
ACCURIN
CREDIT: UNIVERSITY OF MISSOURI
CONTINUED FROM PAGE 12
Dr. Bi-Botti Youan and his colleagues at the University of Missouri (pictured
here) developed a nanofiber-based delivery system designed to stop HIV
transmission through the vaginal mucosa.
Nanofiber vs. HIV
Novel nanofiber-based technology
developed at University of Missouri could
help prevent HIV/AIDS transmission
BY JEFFREY BOULEY
SAN DIEGO—The American Asso-
ciation of Pharmaceutical Scientists (AAPS) signaled what could
be a breakthrough in fighting
human immunodeficiency virus
(HIV) infection when
it announced that its
2014 AAPS Annual
Meeting and Exposition
in November would
feature a research presentation related to the
development of a novel topical
microbicide loaded with hyaluronic
acid (HA) nanofibers that could
potentially prevent transmission
of HIV through the vaginal mucosa.
HIV, the AAPS notes, is an
infectious virus that attacks T
lymphocytes, and over time, HIV
dramatically depletes the body’s T
cell population, leaving the body
defenseless against opportunistic
pathogens. Estimates are that some
1.2 million people aged 13 years and
older are living with HIV infection
in the United States alone, including more than 180,000 who are
unaware that they have the virus.
To date, of course, there is no functional cure for HIV infection or the
condition AIDS that results from
it. Currently available anti-HIV
drug delivery methods are formulated as gels and suppositories, the
AAPS notes, but can lack appropriate vaginal retention, are prone to
medicine leakage and
may cause uncomfortable wetness.
To address these
issues, Dr. Bi-Botti
Youan and his colleagues at the University of Missouri–Kansas City
School of Pharmacy developed
an anti-HIV drug loaded onto a
mucoadhesive HA nanofiber delivery system. The idea behind this
delivery system is that it will offer
a “triggered release” upon exposure to semen fluid during sexual
intercourse, thus preventing HIV
transmission through the vaginal
mucosa.
As the AAPS describes the study
conducted at the University of
Missouri, the researchers used an
electrospinning method to prepare
the nanofibers loaded with tenofovir, a topical anti-HIV compound.
Both semen enzyme-dependent
TOOLS &
TECHNOLOGY
HIV CONTINUED ON PAGE 15
“The success of vaginal drug delivery
systems depends on the length of time
that the drug-containing formulation
remains at the site of administration. The
mucoadhesive nanofibers developed in this
study could be beneficial by causing much
less discomfort and reducing the dosing
frequency simultaneously due to their
prolonged retention at the target site.”
Dr. Bi-Botti Youan of the University of
Missouri–Kansas City School of Pharmacy
will pay BIND a fee and then
royalties on any drug sales.
“This is an exciting and unique
collaboration for BIND as it provides us with novel proprietary
payloads to develop Accurin
product candidates for our internal pipeline,” said Scott Minick,
CEO of BIND, in a statement.
“The structure of this agreement marks an advancement in
our collaboration approach and
demonstrates the strength of our
leadership position in the field of
nanomedicine.”
The lynchpin of the partnership is BIND’s Accurin nanoparticles, which encapsulate cancerkilling drugs in a biodegradable
polymer shell that can bring
them specifically to cancer cells,
while avoiding healthy ones. The
two potential drugs from Merck
to serve as the first two anticancer agents under the new agreement are both kinase inhibitors.
For more information, visit www.DDN-News.com
“Using our nanomedicine platform, we
believe that an Accurin containing
vincristine has the potential to overcome
these liabilities and emerge as a potent
and well-tolerated drug with utility
across a broad range of tumor types.
BIND-510 is designed to concentrate
high levels of vincristine in tumors while
limiting exposure to healthy tissue.”
Scott Minick, CEO of BIND Therapeutics
to overcome these liabilities and
emerge as a potent and welltolerated drug with utility across
a broad range of tumor types.
BIND-510 is designed to concentrate high levels of vincristine in
tumors while limiting exposure
to healthy tissue.”
“We are in the process of
selecting the lead formulation
of BIND-510 and initiating INDenabling tox studies and manu-
“Merck is focused on exploring
immuno-oncology and other promising
pathways, and we look forward to
combining compounds from our
oncology portfolio with BIND’s
nanomedicine technology platform.”
Dr. Eric Rubin, vice president of
clinical oncology for Merck
Research Laboratories
“To select our next product
candidate, we evaluated a broad
range of therapeutic payloads
and targeting ligand combinations to identify Accurin product
concepts that we believe would
have a meaningful impact on
cancer treatment,” Minick tells
DDNews, describing the thought
process behind BIND’S product
strategy. “We selected PSMAtargeted vincristine as our lead
candidate.”
Vincristine is a clinically validated and highly potent vinca
alkaloid microtubule-disrupting
agent predominantly used in the
CHOP chemotherapy regimen
for non-Hodgkin’s lymphoma,
Minick explains.
“While vincristine and the
broader vinca alkaloid class are
well established in both solid
tumors and hematologic malignancies, their clinical utility in
conventional form is limited
by severe toxicities, specifically
cumulative and sometimes irreversible neuropathy,” Minick says.
“This limits the dose and duration of treatment, which prevents
vincristine from achieving its full
therapeutic potential across a
broad range of tumor types. Using
our nanomedicine platform, we
believe that an Accurin containing vincristine has the potential
facturing scale-up for an IND
submission in 2016,” he adds.
“We plan to develop BIND-510
in both solid and hematological malignancies, and will have
more specifics on tumor types as
we get closer to the IND filing.”
Current treatment standards
in oncology include many compounds that are prevented from
achieving their full therapeutic
potential due to on-target but
off-tissue toxicities that limit the
drug from achieving maximum
therapeutic effectiveness, he
notes, adding, “This is because
tumor cells can be virtually identical to healthy cell types in many
respects, including sensitivity
toward cancer drugs. Our nanomedicine platform is designed to
maximize the efficacy of highly
potent compounds that can benefit from the ability of an Accurin
to better distinguish between
healthy and tumor tissue. By
combining prolonged circulation,
tumor targeting and controlled
and timely release of the therapeutic payload, Accurins have the
potential to significantly increase
the clinical benefit, potentially
resulting in efficacy and safety
currently not achievable with conventional treatment standards.”
Accurins increase the concentration and duration of a broad
range of therapeutic payloads at
disease sites when compared to
payloads administered in conventional form, he says.
In the near term, this agreement is unique for BIND because
it enables the company to develop internal product candidates
utilizing Merck-supplied pipeline molecules, one of which is
a kinesin spindle protein (KSP)
and the other of which is a pololike kinase 1 (PLK1).
“Our collaboration with Merck
represents a new type of agreement that provides us with access
to innovative proprietary therapeutic payloads well suited to the
Accurin platform,” Minick says.
“Both KSP and PLK1 generated
a great deal of excitement in the
oncology community a few years
ago as key regulators of cellular
mitosis that are essential to the
proliferation of cancer cells. PLK1
and KSP inhibitors showed strong
promise preclinically, but not in
the clinic due to toxicity issues.”
The high potency and narrow
therapeutic window of the Merck
compounds make them excellent
candidates for the Accurin technology, he adds, saying, “Based
on Merck’s extensive preclinical data for both compounds
and our unique technology, we
believe that these promising antimitotic agents have the potential
to become significant additions
to the armamentarium of novel
cancer therapies.”
Overall, this agreement allows
both companies to discover and
develop novel nanomedicines
for oncology by leveraging
BIND’s proprietary technology
for targeted Accurins and novel,
potent payloads from Merck’s
oncology pipeline.
“We are pleased to collaborate with BIND Therapeutics to
expand Merck’s active oncology
discovery programs,” stated Dr.
Eric Rubin, vice president of clinical oncology for Merck Research
Laboratories, in a news release.
“Merck is focused on exploring
immuno-oncology and other
promising pathways, and we
look forward to combining compounds from our oncology portfolio with BIND’s nanomedicine
technology platform.” n
EDITCONNECT: E011509
For more information, visit www.DDN-News.com
MICRO
CONTINUED FROM PAGE 12
link to the microbiome, according to Alm: “Microbiome-based
medicine is poised to revolutionize patient care for IBD and many
other diseases in the gastrointestinal tract,” he says. “Our goal is to
develop new treatment options—
personalized to an individual’s
microbiota and based on natural
or engineered microorganisms—
that have higher efficacy and fewer
side effects than conventional
drug treatments.”
“ Today, low- cost genetic
sequencing and high-powered
computational methods give us
an unprecedented ability to collect information about the human
microbiome, but our ability to
translate this data into usable
knowledge is lagging behind,” says
Arup K. Chakraborty, the Robert
MIT (pictured here) will be home for the Center for Microbiome Informatics and
Therapeutics, a joint effort with Massachusetts General Hospital to advance
understanding of the microbiome’s role in human biology.
The center will have three core
functions: to advance the field by
funding research proposals; to
help individual research projects
proceed more efficiently through
shared services, such as a regional
sample facility or support for regulatory compliance; and to draw
new talent to microbiome research
by promoting the field within the
academic community.
The center’s initial flagship project will focus on inflammatory
bowel disease (IBD). Individuals
with IBD, which includes conditions such as ulcerative colitis and
Crohn’s disease, suffer from chronic
inflammation of the digestive tract
and experience severe diarrhea,
pain, fatigue and weight loss.
IBD is known to have a strong
JANUARY 2015 | | DDNEWS 15
“Today, low-cost genetic sequencing and
high-powered computational methods give
us an unprecedented ability to collect
information about the human microbiome,
but our ability to translate this data into
usable knowledge is lagging behind.”
Arup K. Chakraborty, director of the MIT
Institute for Medical Engineering and Science
CREDIT: DRKENNETH
collaborations at the junction of
clinical practice, basic research,
computational biology and engineering—critical disciplines for
gathering and analyzing vast quantities of data related to the diverse
types of bacteria within the human
body and their interactions with
each other and the body’s own
cells and organs. The ultimate goal
is to develop tools and techniques
for treating diseases and conditions
linked to an altered microbiome.
The new center’s co-directors are
Eric Alm, an associate professor of
biological engineering at MIT, and
Ramnik Xavier, chief of gastroenterology and director of the Center for the Study of Inflammatory
Bowel Disease at MGH. Under
their guidance, the center will
seek to develop a regional ecosystem together with other hospitals,
universities and research institutions. Collaboration between academic investigators and real-world
clinicians is vital to the center’s
purpose, according to Xavier, who
also serves as the Kurt Isselbacher
Professor of Medicine at Harvard
Medical School.
RESEARCH & DEVELOPMENT
T. Haslam Professor of Chemical
Engineering, Physics, Chemistry
and Biological Engineering at MIT,
and director of the MIT Institute
for Medical Engineering and Science (IMES). “This center is built
around a bold idea: to accelerate
our progress toward a world in
which conditions with a genesis in
the microbiome can be prevented
and treated by solutions derived
from a deep scientific understanding of the microbiome.”
The center introduces a new
research and academic component to MIT and adds an important pillar to the formal strategic
partnership announced by MIT
and MGH last month. It is also a
key component of IMES, which
was established at MIT in 2012 to
tackle some of the world’s biggest
health challenges through interdisciplinary approaches at the intersection of engineering, science and
clinical medicine. Major funding
to support the center’s launch was
provided by the Neil and Anna Rasmussen Foundation.
“Molecular biologists, microbiologists and cell biologists seek
to understand microbe/microbe
and microbe/host cell function
and communication,” Xavier says.
“Immunologists, geneticists and
genomics researchers drive progress. To this wealth of information, clinicians contribute patientbased insights and gain potential
targets for therapeutics. We want
this center to be a convening hub
for strengths that are distributed
across disciplines and throughout
different institutions in the New
England region.”
Until a few years ago, researchers studied the microbiome by carefully separating individual strains
and culturing them in isolation,
a time-consuming method that is
biased toward species that grow
well in the laboratory. Today, however, researchers and doctors can
take advantage of faster, low-cost
genomic tools that allow them to
study the entire bacterial system
of individual patients. These tools
have opened a window into the balance of human cells and the bacteria, viruses and fungi that colonize
and interact within the body.
Based on this knowledge, potential future treatments for IBD and
other conditions might include
simple dietary adjustments; targeted therapies designed to remove,
add or even modify specific bacteria; or medical interventions based
on reprogramming an individual’s
immune system. “We need to
develop a toolkit for engineering
the human microbiome,” Alm says.
Both Alm and Xavier emphasize
that the center’s long-term purpose
is to expand the breadth and depth
of this emerging field. To that end,
the center will also support smaller-scale “innovation projects” that
would not otherwise receive funding due to their cross-disciplinary
or exploratory nature. While IBD
is the focus of the initial flagship
project, the center is designed to
foster opportunities to explore the
impact of the microbiome on systemic autoimmune diseases, such
as multiple sclerosis, Type 1 diabetes and arthritis as well as other
disorders, such as autism, obesity,
acne and allergies. n
EDITCONNECT: E011510
More than 1 million Americans aged 13 years and older are living
with HIV infection, according to government estimates. Researchers
at the University of Missouri have loaded an anti-HIV drug onto a
mucoadhesive hyaluronic acid nanofiber delivery system to develop
an option they hope will help stem the rate of transmission.
HIV
CONTINUED FROM PAGE 14
nanofiber degradation and drug
release were then measured
using chemical and analytical
assays. The cytotoxic effects of
the nanofibers on human vaginal cells and on the Lactobacilli
bacteria present in vaginal flora
were also assessed.
“The success of vaginal drug
delivery systems depends on
the length of time that the
“The nanofiberbased formulation
offers various
potential advantages
in vaginal drug
delivery, including
the ability to adapt
delivery systems for
different medical
needs, with no
leakage or
messiness after their
application.
Furthermore, this
technology could be
beneficial in
protecting drug
molecules against
enzymatic and other
degradation that can
occur in the body.”
American Association
of Pharmaceutical
Scientists
drug-containing formulation
remains at the site of administration,” according to Youan.
“The mucoadhesive nanofibers
developed in this study could
be beneficial by causing much
less discomfort and reducing
the dosing frequency simultaneously due to their prolonged
retention at the target site.”
As the AAPS notes, “The
nanofiber-based formulation
offers various potential advantages in vaginal drug delivery,
including the ability to adapt
delivery systems for different
medical needs, with no leakage
or messiness after their application. Furthermore, this technology could be beneficial in protecting drug molecules against
enzymatic and other degradation
that can occur in the body. Since
human semen is the carrier of
HIV virus transmission during
male-to-female intercourse, a
semen enzyme-triggered nanofiber delivery system as used in
this study has the potential to
inactivate or kill the HIV virus
prior to exposure and penetration of the vaginal mucosa.”
The next step for Youan and
his colleagues is to assess the
safety and efficacy of the HAbased nanofiber templates, and
they will conduct in-vivo studies
using animal models to characterize the viral transmission,
inhibition, potential biodistribution, pharmacokinetics, vaginal retention time, safety and
immunological responses to the
nanofibers. n
EDITCONNECT: E011511
16 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
PRECLINICAL
BR IEFS
CB-839 shows efficacy
SOUTH SAN FRANCISCO, Calif.— Biotechnology
company Calithera Biosciences Inc. has released
preclinical data for CB-839, its lead anticancer
therapeutic candidate. The compound is a potent,
selective, orally bioavailable glutaminase inhibitor currently under investigation in Phase 1 clinical trials as a treatment for multiple myeloma.
Myeloma cells that did not express high levels of
pyruvate carboxylase proved sensitive to CB-839,
and those CB-839-sensitive cells presented with
different metabolic profiles from those of insensitive cells. Metabolic stress induced by CB-839
resulted in sustained inhibition of mTORC1 in sensitive cells, with downstream effects on protein
synthesis, nucleotide production and glycolysis.
In a separate preclinical study of CB-839’s antitumor activity in combination with pomalidomide,
the combination demonstrated synergistic antiproliferative effects in IMiD-resistant cells. CB-839
also demonstrated significant single-agent antitumor efficacy and enhanced antitumor activity
when combined with pomalidomide in a multiple
myeloma xenograft model.
recAP improves mineralization
in hypophosphatasia models
Better together?
Getting the
facts on FACT
Combination cancer
immunotherapy regimen
shows promise for
systemic immune
response to cancer cells
BY JIM CIRIGLIANO
CBL0137 found to be
effective in pancreatic
cancer by targeting
cancer stem cells
CAMBRIDGE, Mass.—Clinical-stage biophar-
BY KELSEY KAUSTINEN
maceutical company Idera Pharmaceuticals
recently presented promising preclinical data
for cancer immunotherapy, with its intratumoral compound IMO-2055 demonstrating potent and systemic antitumor activity in
well-established models of bladder, colon and
lung cancer. The company presented its findings at the American Association for Cancer
Research (AACR) Tumor Immunology and
Immunotherapy Meeting in Orlando, Fla.,
in December 2014.
According to the company, preclinical data
showed that cancer immunotherapy with intratumoral injections combining IMO-2055 and
ipilimumab demonstrated potent and systemic
antitumor activity in multiple preclinical models. IMO-2055 is one of Idera’s synthetic oligonucleotide-based agonists of Toll-like receptor
BUFFALO, N.Y.—Pancreatic cancer is
one of the most aggressive types of cancer, presenting with some of the worst
survival rates. While chemotherapeutic
regimens exist, patients with this cancer type are prone to drug resistance.
As such, the publication of recent studies from Cleveland BioLabs Inc. and
Roswell Park Cancer Institute detailing the efficacy of the small molecule
CBL0137 in pancreatic cancer models
could offer some hope for patients.
Idera recently presented promising preclinical
data for its intratumoral compound IMO-2055
in well-established models of colon cancer, as
well as bladder and lung cancer.
(TLR) 9, and ipilimumab is a U.S. Food and
Drug Administration (FDA)-approved checkpoint inhibitor targeting cytotoxic T-lymphoIDERA CONTINUED ON PAGE 17
IN THIS SECTION
Bone/tooth disease
recAP improves mineralization
in hypophosphatasia models................... 16
Oncology
Better together?...................................... 16
CB-839 shows efficacy............................ 16
Getting the facts on FACT....................... 16
Programmed hematopoietic
cells show potential................................ 16
Ophthalmology
Going after vision loss with MANF......... 18
At the 56th Annual Meeting and Exposition of the American Society of Hematology in December,
Fate Therapeutics released preclinical data highlighting the pharmacological properties of
ex-vivo programmed hematopoietic cells sourced from mobilized peripheral blood.
Programmed
hematopoietic cells
show potential
SAN DIEGO—Fate Therapeutics Inc. is a
clinical-stage biopharmaceutical company
engaged in the discovery and development
of pharmacologic modulators of adult stem
“These data reinforce our growing
base of evidence regarding the
potentially broad efficacy of Curaxin
CBL0137’s mechanism of action,” says
Dr. Andrei Gudkov, senior vice
president of basic science at Roswell
Park Cancer Institute and chief
scientific officer of Cleveland BioLabs.
cells to treat severe, life-threatening orphan
diseases, including hematologic malignancies, lysosomal storage disorders (LSDs) and
muscular dystrophies. Incorporated on April
Studies detailing CBL0137’s preclinical efficacy appeared in Oncotarget in a paper titled “Curaxin CBL0137
eradicates drug resistant cancer stem
cells and potentiates efficacy of gemcitabine in preclinical models of
pancreatic cancer.” Cleveland BioLabs and Roswell Park Cancer Institute are studying CBL0137 both as a
monotherapy and in combination with
gemcitabine, the current standard of
care, in models of pancreatic ductal
adenocarcinoma (PDA) and models
of gemcitabine-resistant tumors. The
studies were conducted by researchers at Roswell Park, SUNY Downstate
FATE CONTINUED ON PAGE 18
FACT CONTINUED ON PAGE 19
Fate Therapeutics demonstrates treatment option that
could be life-saver for people with hematologic malignancies
BY ILENE SCHNEIDER
CREDIT: ROSWELL PARK CANCER INSTITUTE
shared preclinical data on its drug candidate recAP
(recombinant human Alkaline Phosphatase) for the
treatment of the rare disease hypophosphatasia,
which appeared in Bone. Hypophosphatasia, a
mineralization disorder that causes soft bones
(rickets or osteomalacia) and defects in teeth and
periodontal tissues, affects an estimated one in
100,000 newborns. AM-Pharma’s paper detailed
how recAP increased mineralization of bone and
teeth and prevented seizures. Mice with severe
hypophosphatasia received daily subcutaneous
injections of recAP in 1, 8 or 16 mg/kg doses from
birth up to 53 days, and as a result saw normal
lifespans and body weights, while untreated mice
died after 20 days. Imaging showed improved mineralization of cortical and trabecular bone as well
as secondary ossification centers in longer bones.
Additionally, treated mice displayed no evidence
of craniosynostosis or ectopic calcification.
CREDIT: FATE THERAPEUTICS
BUNNIK, The Netherlands—AM-Pharma B.V. recently
PRECLINICAL
For more information, visit www.DDN-News.com
IDERA
CONTINUED FROM PAGE 16
cyte-associated protein 4 (CTLA-4).
The findings presented at the
meeting summarized several studies evaluating monotherapy with
IMO-2055 as well as a combination
regimen in which both IMO-2055
and ipilimumab were administered
via intratumoral injections. The
results of these studies showed that
intratumoral injections of IMO2055 inhibited the growth of treated and distant tumors, measured by
tumor volume and histology. Compared to monotherapy with either
agent, the combination of the two
agents demonstrated increased
and sustained systemic inhibition
of tumor growth. In addition, the
studies identified statistically significant increases in cytotoxic T cells
against two tumor-specific antigens
(AH1 and β-gal) expressed in treated and distant tumors, respectively,
for the combination therapy versus
monotherapy with either agent.
“The data showed that IMO2055 and ipilimumab injections
directly into a tumor stimulated
a potent immune response and
greater inhibition of tumor growth
compared to treatment with either
agent alone,” says Dr. Sudhir
Agrawal, president of research at
Idera. “Importantly, these injections into a single tumor also led
to a systemic immune response
that inhibited the growth of distant,
untreated tumors.”
The findings are consistent
with Idera researchers’ belief that
IMO-2055 and ipilimumab may
have complementary mechanisms
of action, which would enhance
their effectiveness when administered together as part of a cancer
immunotherapy regimen. Other
combination regimens with IMO2055 and different checkpoint
inhibitors—several of which have
been approved by the FDA or are in
late-stage clinical trials—also may
be effective, Agrawal says.
IMO-2055 is an investigational
agonist of TLR 9 discovered and
developed by Idera that activates
TLR 9 signaling to stimulate an
immune response against tumorspecific antigens. TLRs play a key
role in alerting the body’s innate
immune system to invading pathogens as well as damaged or dysfunctional cells such as cancer cells.
Ipilimumab, a compound developed by Bristol-Myers Squibb Co.,
is approved by the FDA for the
treatment of unresectable or metastatic melanoma.
“By targeting regulatory checkpoint pathways such as CTLA-4 or
programmed cell death protein 1,
checkpoint inhibitors are designed
to enable the immune system to
recognize tumor cells,” says Agrawal. “A TLR 9 agonist such as IMO2055 has the potential to enhance
the anti-tumor response by activating TLR signaling.”
In simple terms, Agrawal explains,
the checkpoint inhibitor is designed
to weaken the tumor’s defenses
against immune attack, while the
TLR 9 agonist is designed to enhance
an antitumor immune response.
“We are continuing to conduct
preclinical studies of IMO-2055 in
combination with various checkpoint inhibitors to further characterize potential cancer immunotherapy combination regimens,”
says Agrawal. “In parallel, we are
assessing our options to advance an
immunotherapy program into clinical development. We look forward
JANUARY 2015 | | DDNEWS 17
“The data showed that IMO-2055 and ipilimumab injections directly into
a tumor stimulated a potent immune response and greater inhibition of
tumor growth compared to treatment with either agent alone.
Importantly, these injections into a single tumor also led to a systemic
immune response that inhibited the growth of distant, untreated tumors.”
Dr. Sudhir Agrawal, president of research at Idera Pharmaceuticals
to unveiling those plans next year.”
Additional candidates based on
Idera’s discovery platform include
IMO-2125 (another synthetic
oligonucleotide-based TLR 9 ago-
nist) and IMO-8400, an antagonist of TLRs 7, 8 and 9 designed
to inhibit TLR-mediated immune
responses. Two Phase 1/2 clinical
trials of IMO-8400 are underway
in patients with genetically defined
forms of B-cell lymphoma in which
over-activated TLR signaling contributes to the disease process. ■
EDITCONNECT: E011512
Cambridge Healthtech Institute’s Fourteenth Annual
APRIL 21 – 23, 2015
SEAPORT WORLD TRADE CENTER
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PRECLINICAL
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Going after vision loss with MANF
Amarantus announces
positive preclinical data
on effects of MANF on
vision in model of
retinitis pigmentosa
BY LLOYD DUNLAP
SAN FRANCISCO—Amarantus BioScience
Holdings Inc., a biotechnology company
focused on the development of diagnostics
and therapeutic products in the areas of neurology, psychiatry, ophthalmology and regenerative medicine, has announced positive
effects of mesencephalic-astrocyte-derived
neurotrophic factor (MANF) for the protection from vision loss in an animal model of
retinitis pigmentosa (RP). MANF was discovered utilizing Amarantus’ proprietary PhenoGuard Protein Discovery Engine.
MANF, the company’s lead therapeutic
program, is a targeted therapeutic to address
the underlying programmed cell death (apoptosis) associated with a wide range of devastating human disorders with a priority to
identify drugable orphan indications, including RP.
Amarantus President and CEO Gerald
E. Commissiong led the Neurotrophic Factors Group at the U.S. National Institutes of
Health in the 1990s, where he became keenly
interested in astrocytes because they dramatically outnumber neurons in terms of number of cells and morphological complexity.
After years of research, his team demonstrated that astrocytes from one region of the
brain (substantia nigra) secreted molecules
that protected neurons from that region of
the brain (dopaminergic neurons of the substantia nigra) better than astrocytes from any
other brain region. Shortly after his group
FATE
CONTINUED FROM PAGE 16
27, 2007, the company’s approaches use pharmacologic modalities, including small molecules and therapeutic proteins, to enhance
the therapeutic potential of adult stem cells.
Adult stem cells play a key role in the
growth, maintenance and repair of many tissues and organ systems in the body. Because
they can self-renew and regenerate and
repair diseased or damaged tissue, adult stem
cells hold considerable therapeutic promise
according to the company.
At the 56th Annual Meeting and Exposition of the American Society of Hematology (ASH) in December, Fate Therapeutics
released preclinical data highlighting the
pharmacological properties of ex-vivo programmed hematopoietic cells sourced from
mobilized peripheral blood. Using a newly
identified combination of two small-molecule modulators, scientists from the company
demonstrated that both T cells and CD34+
cells from mobilized peripheral blood can be
modulated ex vivo, with preclinical evidence
pointing to the programmed hematopoietic
cells having improved therapeutic potential.
The company’s hematopoietic stem cell
(HSC) modulation platform focuses on the
ex-vivo pharmacologic optimization of HSCs,
which are adult stem cells that regenerate
all types of blood cells throughout a person’s
lifespan. HSCs have been used for the cura-
published its findings, another group published an almost identical set of results, giving Commissiong confidence that they were
on the right track.
“From there, another important issue
needed to be resolved,” Commissiong realized. “In order to use astrocytes as a tool for
discovering the neurotrophic factors responsible for the protection we were seeing, we
needed a stable source of astrocytes capable
of being used in a systematic screening process over and over again. It was here that I
reached into some of my early research experience to engineer some proprietary methods
to immortalize the astrocytes we were using
to generate the initial results in order to turn
them into stable cell lines that could be used
for neurotrophic factor discovery.”
In the current study, the aim was to evaluate the efficacy of protecting visual acuity by
a single intravitreal injection of MANF in the
rd10/rd10 genetic mouse model of RP. These
animals carry a spontaneous missense point
mutation in Pde6b (cGMP phosphodiesterase
6B, rod receptor, beta polypeptide). Mutations
in this gene are found in human autosomal
recessive RP. Visual acuity was determined by
measuring the spatial frequency threshold by
optokinetic tracking. This method allows for
a non-invasive assessment of visual acuity in
rodents and higher species, including humans.
A single intravitreal administration of
MANF after the onset of retinal degeneration
on day 31 resulted in a statistically significant
protective effect on visual acuity on day 38
and day 45, as compared to vehicle-treated
animals. This is the first observation of MANF
providing a functional benefit on vision in a
model of RP. These data complement previously announced effects of MANF on preserving retinal morphology in RP models. The
“While hematopoietic
stem cell transplantation
has proven curative
potential, a significant
need remains to reduce
the morbidity and
mortality associated with
the procedure, including
the risk of T cell-mediated
complications such as
viral infections, graft vs.
host disease and delayed
immune reconstitution.”
Dr. Christian Weyer,
president and CEO of
Fate Therapeutics
tive procedure called hematopoietic stem cell
transplant (HSCT).
Hematopoietic stem cell transplantation
represents a potentially life-saving treatment
option for children and adults afflicted with
hematologic malignancies. The number of
procedures performed has increased steadily
over the past two decades. Currently, about
Amarantus recently announced positive
effects of mesencephalic-astrocyte-derived
neurotrophic factor for the protection
from vision loss in an animal model of
retinitis pigmentosa.
experiments were conducted at a leading
ophthalmology contract research laboratory.
“Our results are the first observation
of protection of vision in an RP model by
MANF, and add a seminal functional visual
acuity readout to the initial morphological protection findings reported from the
University of Miami’s Bascom Palmer Eye
Institute,” said Dr. David A. Lowe, president
and CEO of NeuroAssets and member of the
Amarantus board of directors. “These data
further support our focus on ophthalmic
orphan indications, as exemplified by our
recent application to the FDA for orphan
designation in RP.” The company expects to
receive a response in the near future.
“These promising data provide a compelling basis to continue the further development of MANF in RP towards first-in-man
studies,” said Commissiong. “We will contin60,000 HSCT procedures are performed on
a worldwide annual basis.
The company’s product candidate, PROHEMA, is a pharmacologically modulated
HSC therapeutic derived from umbilical
cord blood. It has human proof of concept
for PROHEMA in the clinical setting by demonstrating enhanced and durable engraftment of HSCs within the bone marrow. The
company is advancing PROHEMA in Phase 2
clinical development for hematologic malignancies. It is also engaged in the development of pharmacologically optimized HSC
therapeutics for the treatment of LSDs,
where HSCs have the ability to migrate
to and engraft within the central nervous
system. PROHEMA is produced through a
proprietary, two-hour, ex-vivo programming
process using a small-molecule modulator
(FT1050) that promotes rapid and supraphysiologic activation of genes involved
in the homing, proliferation and survival
of HSCs, which are key biological properties necessary for durable engraftment and
hematopoietic reconstitution.
Fate Herapeutics’ satellite stem cell
(SSC) modulation platform focuses on the
in-vivo pharmacologic activation of SSCs,
which are adult stem cells that regenerate
muscle throughout a person’s lifespan. The
company has identified Wnt7a as a natural
promoter of SSCs to drive muscle regeneration, and it is focused on developing
Wnt7a analogs for the treatment of muscu-
ue moving forward with a strategic development plan focused initially on orphan ocular
diseases, where we see tremendous potential
for MANF. We are hopeful to develop better
treatments for patients suffering from diseases that lead to blindness due to an array
of medical conditions. Ultimately, we believe
proof of concept for MANF in human studies
in ocular diseases will support MANF development in other therapeutic areas where
significant compelling preclinical efficacy
data has been published and confirmed by
independent groups, as well as the company’s
own datasets. We firmly believe MANF has
blockbuster potential in ophthalmology, neurology, cardiology and metabolic disorders,
including diabetes.”
RP is a group of inherited diseases involving retinal degeneration. The cell-rich retina
lines the back inside wall of the eye and is
responsible for capturing images from the
visual field. People with RP experience a
gradual decline in their vision because photoreceptor cells (rods and cones) die. Symptoms
include a progressive degeneration of peripheral and night vision as well as the degeneration in color perception and central vision;
night blindness is one of the earliest and most
frequent symptoms of RP. RP is typically diagnosed in adolescents and young adults. The
rate of progression and degree of visual loss
varies from patient to patient, with most people with RP becoming legally blind by age 40.
There are approximately 100,000 patients in
the United States, 100,000 patients in Europe
and 50,000 patients in Japan diagnosed with
RP, qualifying it as an orphan indication.
There are currently no approved treatments
in the market. It is estimated that RP is a
multibillion-dollar market opportunity. ■
EDITCONNECT: E011515
lar dystrophies. Wnts comprise a range of
19 secreted proteins known to play a key
physiological role in developmental and
regenerative processes.
“While hematopoietic stem cell transplantation has proven curative potential, a significant need remains to reduce the morbidity
and mortality associated with the procedure,
including the risk of T cell-mediated complications such as viral infections, graft vs.
host disease and delayed immune reconstitution,” explains Dr. Christian Weyer, president
and CEO of Fate Therapeutics. Weyer joined
Fate Therapeutics after a 12-year tenure with
Amylin Pharmaceuticals Inc., where he most
recently served as senior vice president of
research and development until the completion of Amylin’s acquisition by Bristol-Myers
Squibb Co. in August 2012.
“We are excited that our ex-vivo programming platform has identified a combination of
small-molecule modulators that promote the
supra-physiologic activation of genes implicated in the cell cycle, immune tolerance and
antiviral properties of T cells, as well as in
the survival, proliferation and engraftment
potential of CD34+ cells,” Weyer adds. “We
believe these findings form a compelling scientific basis to support the clinical evaluation
of ex-vivo programmed mobilized peripheral
blood in patients undergoing hematopoietic
stem cell transplantation for the treatment
of hematologic malignancies.” ■
EDITCONNECT: E011513
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y
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PRECLINICAL
For more information, visit www.DDN-News.com
Pictured here is
Roswell Park Cancer
Institute’s main
clinical facility. The
organization recently
published studies
with Cleveland
BioLabs detailing
the efficacy of
CBL0137 in
pancreatic cancer,
alone and combined
with gemcitabine.
CREDIT: ROSWELL PARK CANCER INSTITUTE
tumor cells than for normal cells.”
The team studied CBL0137 as
both a monotherapy and a combiMedical Center and Buffalo Bionation therapy with gemcitabine
labs, LLC.
using patient-derived PDA xenoCBL0137’s mechanism of
grafts and PANC-1 orthotopic
action consists of the modulatumors. The compound was found
tion of several important sigto be efficacious in mouse models
naling pathways involved in the
of PDA and to enhance the effect
pathogenesis of PDA through
of gemcitabine by causing a sigthe inhibition of the chromatin “Gemcitabine
nificant delay in tumor relapse folremodeling complex, known targets quickly
lowing treatment completion. It is
as FACT (Facilitates chromatin proliferating
tumor cells,
thought that the combined results
transcription), which is fre- because it’s a
arise from CBL0137 targeting canquently overexpressed in several compound which
cer stem cells while also modulatdifferent tumor types. FACT-pos- inhibits DNA
ing the expression of genes affecting
itive tumors are associated with synthesis.
gemcitabine sensitivity.
an aggressive malignant pheno- CBL0137 targets
“We believe there are several
type—that is, a high-grade, met- cancer stem cells,
are
mechanisms
involved in combined
astatic disease with worse over- which
believed to be
toxicity,” says Gurova. “Gemcitabine
all survival outcomes. As noted slowly
on Cleveland BioLabs’ website, proliferating … so targets quickly proliferating tumor
“The interaction of CBL0137 when we combine cells, because it’s a compound which
with FACT complex results in them together, we inhibits DNA synthesis. CBL0137
targets cancer stem cells, which are
simultaneous NF-kB suppres- are kind of
believed to be slowly proliferating …
sion, Heat Shock Factor 1 sup- targeting both
populations of
so when we combine them together,
pression and p53 activation. This cells: quickly
we are kind of targeting both popumodulation of three key cellular proliferating bulk
lations of cells: quickly proliferating
pathways causes suppression of tumor cells and
slowly
bulk tumor cells and slowly prolifcancer cell growth.”
erating cancer stem cells. Plus there
“The DNA in our cells is proliferating
quite long; each chromosome cancer stem cells,” are additional mechanisms involved
says Dr. Katerina
which just make cells more sensitive
is around more than one yard, Gurova, assistant
to gemcitabine.”
and its length can be packed to professor of
“As of today, CBL0137 has been
be quite compact to fit into the oncology in the
shown efficacious in practically any
nucleus of our cells and also to Department of
cancer model tested. And we covbe well organized. So there are Cell Stress
ered many dozens of in-vivo models
special protein complexes which Biology at
Park
of cancer, including all major canhelp to pack this DNA,” explains Roswell
Cancer Institute.
cers and many cancers that belong
Dr. Katerina Gurova, assistant
professor of oncology in the Department of to more rare categories, meaning that we
Cell Stress Biology at Roswell Park Cancer are not restricted to just one or two types of
Institute. “FACT was considered to have this cancer. As Katerina mentioned, the expresbasic housekeeping-like function because sion of FACT is observed in cancer stem cells,
people usually studied it in some unicel- again meaning that practically any type of
lular organisms or in models using tumor cancer should be considered as a potential
cells, but when we looked more carefully, we target for treatment with CBL0137,” says Dr.
found that FACT is present mostly in tumor Andrei Gudkov, senior vice president of basic
cells, and in a very limited amount of normal science at Roswell Park Cancer Institute and
cells. And it’s quite understandable, because chief scientific officer of Cleveland BioLabs.
“These data reinforce our growing base
probably this packaging and unpackaging of
INDIGO_DDN_Ad_2014.04.29.pdf
4/30/2014
1:16:10 PM
of evidence regarding the potentially broad
DNA
is more critical for 1quickly
proliferating
CONTINUED FROM PAGE 16
CREDIT: ROSWELL PARK CANCER INSTITUTE
FACT
JANUARY 2015 | | DDNEWS 19
efficacy of Curaxin CBL0137’s mechanism of
action. The data shared in this publication
and the known role of FACT in the pathogenesis of PDA and viability of cancer stem
cells support our consideration of pancreatic
cancer as a potential indication for Phase 2
development of CBL0137,” he added.
Gudkov notes that hematological malignancies and brain tumors are also indications they are considering as they advance
CBL0137, as the compound has proven capable of passing through the blood-brain barrier.
CBL0137 is undergoing two Phase 1 clinical
trials. In the United States, Curaxin CBL0137
is being evaluated in patients with metastatic
or unresectable advanced solid cancers and
lymphomas in multiple centers, including
Roswell Park Cancer Institute. A Phase 1
study investigating the oral administration
of the compound in patients with advanced
solid tumors that are resistant or refractory to
current standard treatment is also underway.
“Pancreatic cancer is a very challenging
disease that is highly resistant to conventional chemotherapy. CBL0137 has been shown
to be effective in preclinical pancreatic cancer models, including gemcitabine-resistant
tumors. The agent seems to target pancreatic
cancer stem cells and survival pathways, thus
rendering this a very promising treatment
for this disease,” said Wen Wee Ma, associate
professor of oncology in the Department of
Medicine at Roswell Park Cancer Institute
and principal investigator for the intravenous
trial of CBL0137.
Pancreatic cancer stands as the fourth leading cause of cancer-related death in the United
States, with the highest mortality rate of all
major cancers: according to the American Cancer Society, 94 percent of pancreatic cancer
patients will die within five years of diagnosis. ■
EDITCONNECT: E011514
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20 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
Society for Laboratory Automation
and Screening
Walter E. Washington Convention Center Washington, D.C. Feb. 7-11, 2015
n
Step out
along
Innovation
AveNEW
WASHINGTON, D.C.—Innovation AveNEW has become something
of “a traditional highlight” of the annual SLAS Conference and
Exhibition, according to the SLAS. Through this program, SLAS provides startup companies with exposure and prestige by granting
complimentary exhibit space and in-kind support that enables the
company’s participation at the SLAS annual meeting. Innovation
AveNEW participants are selected by a committee of SLAS volunteers that judges applicants based on a set of criteria that includes
the impact of the technology, commercial viability and potential
impact on the field of laboratory automation and technology.
SLAS congratulates the following eight companies from four
different countries that will represent Innovation AveNEW at
SLAS2015:
Ceres Nanosciences in Manassas, Va., is a privately held lifesciences company engaged in the research, development and
commercialization of innovative sample preparation products
based on its proprietary Nanotrap technology, which captures,
enriches and preserves analytes/biomarkers.
Creoptix in Wadenswil, Switzerland, goes for “high-sensitivity
meets label-free by offering best-in-class biosensor devices for
the most demanding applications in life-sciences research and
drug discovery.”
Electrospinning in Oxfordshire, U.K, was launched in 2010
to develop products utilizing the world-class electrospinning
platform at the Rutherford Appleton Laboratory in Oxfordshire.
InnoCyte in Stuttgart, Germany, has developed a technology that standardizes, automates, accelerates and therefore
significantly simplifies and reduces the cost of producing biological cells.
Microscopy Innovations in Marshfield, Wis., is a life-sciences
tools company founded in 2007 to create novel products for
microscopy laboratories.
SiTOOLS in Bavaria, Germany, provides novel tools for RNA
interference around siPOOLs, which are complex pools of accurately defined siRNAs, which show efficient and robust target
gene knockdown to reduce off-target effects and deliver clean
and reliable phenotypic data.
StackWave in Louisville, Ky., comprises a team of software
developers skilled in biotech and pharmaceutical software systems integration.
Telos Scientific in San Diego bridges the gap between science
and engineering to make laboratory automation user-friendly,
highly functional and bottom-line productive.
SLAS invites you to stop by Innovation AveNEW in the
SLAS2015 Exhibition to visit with these companies and see
the technologies that earned them this important distinction. n
n
SLAS GOES EAST
Washington, D.C., will
host ‘what’s new in lab
automation and screening’
for the SLAS2015 meeting
BY LLOYD DUNLAP
WASHINGTON, D.C.—This year marks
a significant milestone for the annual
meeting of the Society for Laboratory
Automation and Screening (SLAS), as
SLAS2015 gets ready to convene Feb. 7-11
at the Walter E. Washington Convention
Center in Washington, D.C.
“This meeting marks the first time
SLAS will hold our annual meeting in
D.C.,” notes Tom Manning, the organization’s director of marketing communications. Formed only four years ago by the
merger of the Society for Biomolecular
Sciences (SBS) and the Association for
Laboratory Automation (ALA), the organization has quickly become the launching pad for what’s new in lab automation
and screening. “We are excited about
D.C. for a number of reasons,” Manning
states, and lists off a few: “The location is
easily accessible for much of the U.S. and
is within driving distance for many East
Coast residents. Furthermore, the D.C.
location should enable more government
scientists—often constrained by travel
and training expenses—to participate in
SLAS2015.”
In 2014, SLAS, headquartered near
Chicago, set in motion a multiyear rotation between San Diego (even-number
SLAS2015 will feature a an extensive products and services exhibition with more than
300 leading, multinational providers. Interactive exhibits, knowledgeable product
experts and vendor-led education enhance the attendee experience.
years) and D.C. (odd-number years) as
the host city for the society’s flagship
annual event.
San Diego readily attracts the biotechnology community, notes SLAS
President Daniel Sipes, who represents
that community in his “day job” with
the Genomics Institute of the Novartis
Research Foundation, where he is the
director of advanced automation technologies. In addition to government
types, Sipes adds that Big Pharma and
European representatives are likely to
find the East Coast location convenient.
Sipes notes that since the merger of
the SBS and the ALA four years ago to
form SLAS, the annual meeting has been
structured with three pillars: education,
exhibits and community. Many attendees, he observes, come principally for
one of the three, particularly the exhibits,
but post-event surveys have indicated all
three aspects rate highly with attendees.
In terms of “education,” which we
at DDNews tend to focus on in these
show previews, SLAS2015 will feature
140 podium presentations across seven
educational tracks, which are: Assay
Development and Screening, Automation and High-Throughput Technologies,
Bioanalytical Techniques, Biomarker
Discovery and Applications, Drug Target
Strategies, Micro- and Nanotechnologies
and, finally, Informatics.
Manning notes that especially highprofile podium presentations (and
authors) scheduled for SLAS2015
include the 10 finalists for the annual
SLAS Innovation Award:
Droplet Microfluidics for HighThroughput Analysis and Sensing by
Prof. Robert Kennedy, University of
Michigan
Digital Microfluidic Immunocytochemistry in Single Cells (DISC) by Prof.
Aaron Wheeler, University of Toronto
■■
■■
Innovation AveNEW is an area of the SLAS annual meeting exhibitions dedicated to
new and emerging start-ups. Eight companies from four countries will be represented
on Innovation AveNEW at SLAS2015.
SLAS CONTINUED ON PAGE 22
SLAS2015
22 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
SLAS
Keynote
addresses at
SLAS2015
CONTINUED FROM PAGE 20
An Automated Open Platform
for Exclusion-based Sample Preparation: Getting More Information
from Limited Patient Samples by
David J. Guckenberger, University
of Wisconsin, Madison
Droplet-Based Three-Dimensional Cell Migration Assay with
Flow Cytometry-Based Automated
Analysis by Dr. Marie-Elena Brett,
University of Minnesota
Novel Acoustic Loading of
a Mass Spectrometer—Towards
Next-Generation High-Throughput MS Screening by Dr. Jonathan
Wingfield, AstraZeneca, Discovery
Sciences
Automation of Droplet Manipulation Using Electrowetting on
Film by Dr. Thomas D. Perroud,
eFluidics
Annotating Biological Activities of Compounds by High-content Pathway Profiling Assays by
Dr. Sergei S. Makarov, ATTAGENE
The Simoa HD-1 Analyzer:
A Fully automated, Multiplexed
Immunoanalyzer with Single Molecule Sensitivity by Dr. David C.
Duffy, Quanterix Corp.
Zero Background in Homogeneous Proximity Assays Using Thermofluorimetric Analysis (TFA) for
Quantitation of Attomole Protein
Levels in Serum by Dr. Joonyul
Kim, Auburn University
Bioinspired Spleen-on-a-chip
for Sepsis Therapy by Dr. Joo Hun
Kang, Wyss Institute/Harvard
University
Interested parties can see presentation and session details for
the items above and others, as well
as the latest version of the scientific
program, on the SLAS2015 Event
Scheduler at www.eventscribe.
com/2015/SLAS2015/
Special Sessions are also a highlight of the scientific program,
Manning notes.
“Three unique Special Sessions
have been curated especially for
SLAS2015,” he observes. “Each of
these includes multiple presenta■■
■■
With a theme of focusing on leveraging
science to advance the health of
humankind, the keynote addresses at
SLAS2015 will cover issues that range
from biomimetic micro systems that
feature “organ-on-a-chip” technology to
global health issues.
■■
SLAS2015 will feature a robust lineup of education, including 142 podium
presentations across seven tracks
■■
■■
MONDAY, FEB. 9, 9 A.M.
Donald E. Ingber, M.D., Ph.D.
■■
tions focused on the broader theme
of the session. Special Sessions at
SLAS2015 include: European Government/Foundation Drug Discovery Collaboration; The Commercialization of New Technologies:
From Ideas to Reality (presented by
the SLAS Journal of Laboratory Automation); and An Evening with NIH,
which will be moderated by Chris
Austin, director of the National
Center for the Advancement of
Translational Sciences.”
Keynote presenters include Dr.
Donald Ingber, Judah Folkman Professor of Vascular Biology, professor of bioengineering and founding
director of the Wyss Institute for
Biologically Inspired Engineering
at Harvard University, who will
address SLAS2015 on Monday,
Feb. 9, as well as NIH Director Dr.
Francis Collins on Wednesday, Feb.
11, and Laurie Garrett, author and
CREDIT: DESTINATION DC
■■
Poster presentations complement the technical education at SLAS2015.
The Walter E. Washington Convention Center, a 2.3 million-square-foot
conventions and meetings facility, is equipped to handle events of all sizes,
from small groups and break-out meetings to events for 500 to 42,000
attendees.
noted authority on global health
issues on Wednesday night.
And then there is the “exhibit”
part of the three pillars of SLAS
meetings, which Manning calls
“another highlight.”
“We expect more than 300
exhibiting companies,” he says.
“In addition to traditional booths,
many companies are also delivering Exhibitor Tutorials, thereby
adding to the technical education
SLAS2015 attendees are eligible to
receive. The exhibit hall will also
host our traditional SLAS Innovation AveNEW, which is a segment
of the show floor featuring eight
start-up companies from around
the globe with especially notable
technologies. As Innovation AveNEW participants, these companies
received complimentary exhibit
space and other in-kind support as
part of SLAS’ mission to nurture
scientific technology innovation.”
“Intelligent Network Building is
another cornerstone of this annual
event,” Manning notes, bringing
in the third pillar of “community,”
which often revolves around meals,
receptions and other events that
facilitate attendee interaction. “A
highlight of our networking lineup
is the Tuesday evening event at the
Smithsonian National Air & Space
Museum,” he states.
The Career Connections offerings have also been enhanced for
SLAS2015. This programming
includes career-focused workshops,
the opportunity for individual
resume review, interview training, a
job board and mentoring opportunities with professional scientists and
researchers local to D.C. Similarly,
a robust lineup of education and
networking for students and early
career professionals is also on tap. n
EDITCONNECT: E011528
CREDIT: SAM OGDEN
■■
Founding director of the Wyss Institute for Biologically
Inspired Engineering at Harvard University, Judah
Folkman Professor of Vascular Biology at Harvard
Medical School and Boston Children’s Hospital and
professor of bioengineering at the Harvard School of
Engineering and Applied Sciences
Dr. Donald Ingber is a founder of the emerging field of biologically inspired engineering, and at the Wyss Institute, he oversees a multifaceted effort to identify
the mechanisms that living organisms use to self-assemble from molecules and
cells and to apply these design principles to develop advanced materials and
devices for healthcare and to improve sustainability. He has made major contributions to mechanobiology, tissue engineering, tumor angiogenesis, systems
biology and nanobiotechnology. He has authored more than 375 publications
and 85 patents, and has received numerous honors, including the Holst Medal,
Pritzker Award from the Biomedical Engineering Society, Rous-Whipple Award
from the American Society for Investigative Pathology, Lifetime Achievement
Award from the Society of In Vitro Biology and the Department of Defense
Breast Cancer Innovator Award.
WEDNESDAY, FEB. 11, 8:30 A.M.
Francis Collins, M.D., Ph.D.
Director of the U.S. National Institutes of Health (NIH)
As the head of the NIH, Dr. Francis S. Collins oversees the
work of the largest supporter of biomedical research in the
world, spanning the spectrum from basic to clinical research.
Collins is a physician-geneticist noted for his landmark discoveries of disease genes and his leadership of the international
Human Genome Project, which culminated in April 2003 with the completion of a
finished sequence of the human DNA instruction book. He served as director of the
National Human Genome Research Institute at the NIH from 1993 to 2008. Before
coming to the NIH, Dr. Collins was a Howard Hughes Medical Institute investigator
at the University of Michigan. He is an elected member of the Institute of Medicine
and the National Academy of Sciences, was awarded the Presidential Medal of
Freedom in November 2007 and received the National Medal of Science in 2009.
WEDNESDAY, FEB. 11, 3:45 P.M.
Laurie Garrett
Author, journalist and authority on global health issues
Laurie Garrett is one of America’s leading commentators on
global health issues. She is the only person to win the three
P’s of journalism: The Pulitzer Prize, the Peabody Award and
the Polk Award. She is a senior fellow for global health at the
Council on Foreign Relations and is the bestselling author of
The Coming Plague and Betrayal of Trust. She has written for
Foreign Affairs, Esquire and The Washington Post, and has appeared frequently on
television shows, such as “Nightline,” “Charlie Rose” and “Oprah.” Garrett also
served as a script consultant to Contagion, the film directed by Steven Soderbergh
and starring Matt Damon. Garrett is a former president and now a member of the
National Association of Science Writers, and has been awarded three honorary
PhDs. Garrett’s long-awaited third book, now in stores, is called I Heard the
Sirens Scream: How Americans Responded to the 9/11 and Anthrax Attacks. n
SLAS2015
For more information, visit www.DDN-News.com
Special Sessions at SLAS2015
SLAS2015 will feature a series of special sessions,
each comprised of multiple presentations dedicated to
especially timely and relevant topical areas.
European Government/
Foundation Drug
Discovery Initiatives
MONDAY, FEB. 9,
10:30 A.M. TO 12:30 P.M.
■■
■■
Moving Research Innovations to the
Market (Presenter: Alicia Löffler,
Innovation and New Ventures
Office, Northwestern University)
Opportunities and Challenges in
Life Sciences R&D (Presenter:
Jeremy Caldwell, Third Rock
Ventures)
■■
Minding the Gaps in Biomedical
Technology Translation (Presenter:
Megan Frisk, Science Translational
Medicine/AAAS)
JANUARY 2015 | | DDNEWS 23
An Evening with NIH
MONDAY, FEB. 9,
6:30 P.M. TO 8:30 P.M.
Join Chris Austin, director of
the National Center for Advancing
Translational Sciences,
as he chairs a special evening
event focused on the array of
programs, services and capabilities
of the National Institutes of
Health (NIH) and how to best
navigate the organization.
Presentations include:
■■
Facilitated Translation Within
Session Chair:
Steven Rees, AstraZeneca
European governmental and charity
agencies are enabling the translation
of academic discovery into health
benefits of economic value by
funding the creation of several novel
models and approaches to drug
discovery. These initiatives have
included the development of new
compound libraries, the
establishment of academic
screening centers and the formation
of innovative partnerships with
industry. Speakers in this special
session explore the interaction of
these initiatives with academia and
pharma, and describe the anticipated
benefit of these programs in terms
of bringing novel projects into the
clinic. Presentations include:
■■
■■
■■
Chemical Biology Consortium
Sweden—Deliveries Including
Scientific Highlights After
Five Years (Presenter: Annika
Jenmalm Jensen, Chemical
Biology Consortium)
EU-OPENSCREEN: Chemical
Tools for the Life Sciences
(Presenter: Philip Gribbon,
ScreeningPort Hamburg)
The European Lead Factory: Game
Changing for Innovative Medicine
(Presenter: Steven van Helden,
Pivot Park Screening Centre)
Opening “The Box of Delights”—
Accessing Pharma to Enhance
Academic Drug Discovery:
(Presenter: Justin Bryans,
MRC Technology)
The Commercialization
of Laboratory
Technologies:
From Ideas to Reality
MONDAY, FEB. 9,
3 P.M. TO 5 P.M.
Presented by the Journal
of Laboratory Automation
Session Chairs: Dean Ho,
University of California, Los
Angeles and Edward Chow,
National University of Singapore
Topics covered in this session
include the process of
commercialization and challenges
that, when overcome, catalyze the
ability to transition a product or
technology from benchtop
innovation to lasting commercial
impact. Presentations include:
■■
Creativity Beyond the Science:
Innovative Ways to Commercialize
an Idea in the Global Industry
(Presenter: Katherine Wang,
BRIM Technology)
© 2015 PerkinElmer, Inc. 400285_09. All trademarks or registered trademarks are the property of PerkinElmer, Inc. and/or its subsidiaries.
■■
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Opera Phenix: More physiological relevance. No compromise.
www.perkinelmer.com/YES
NCATS’ TRND and BrIDGs
Programs (Presenter: Nora
Yang, NIH)
■■
■■
■■
NIH-Industry Partnership to
Discover New Therapeutic Uses
for Existing Molecules (Presenter:
Christine Colvis, NIH)
National Center for Advancing
Translational Sciences SBIR and
STTR Programs: Valuable
Resources for Small Businesses
(Presenter: Lili Portilla, NIH)
NCI Experimental Therapeutics
Program (Presenter: Barbara
Mroczkowski, NIH) n
SLAS2015
24 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
T
OUTED AS “one of
the select few highly
discreet, automated
employment programs
that brings together its
online professional services with its
respected career center and development sessions at the annual meeting,” SLAS invites attendees to take
advantage of SLAS Career Connections offerings, which include free
career development workshops.
One of these workshops is “Mock
Interviews: Preparation and Practice for Getting the Jobs You Want”
by Dr. Daniel J. Eustace, a professor at the University of Connecticut. Held Tuesday, Feb. 10, from 7
a.m. to 8:15 a.m. (breakfast will be
served), this interactive workshop
invites audience members to play
active roles participating in, providing feedback for and perhaps
coaching how to manage different
kinds of interview scenarios.
All attendees should bring their
current resumes to the workshop
and be prepared to actively participate. Attendees will learn by doing,
by watching others interview, by
discussing alternate approaches and
by internalizing how one would perform if they were in the situation.
In addition, Prof. Eustace provides one-on-one and group career
counseling sessions by appointment at the SLAS Member Center
Monday, Feb. 9, and Tuesday, Feb.
10. Contact Mary Geismann at
[email protected] to schedule
your appointment.
The other three of the four career
development workshops are being
presented by Dr. Joanne Kamens,
executive director of Addgene, who
will cover networking, choosing a
lab and transitioning from academia to industry.
“Not Networking 101—Building
Relationships for Success,” will be
held Monday, Feb. 9, from 7 a.m.
to 8 a.m. (breakfast will be served).
As described by SLAS: Networking
has gotten a really bad name these
days. I take your card, you take my
card and then we don’t call each
other. This workshop is designed
to reintroduce you to how strong
professional relationships can be
necessary for most people to succeed in their careers. It will provide
practical tools for meeting people
and for nurturing new and established connections.
Kamens will conduct “Smooth
transitions—Top 10 List: Things
Scientists Ask About Finding an
Industry Job” on Monday, Feb. 9,
from 12:30 p.m. to 1:30 p.m., and
attendees are asked to bring a box
lunch if they need one. SLAS says
of this workshop: These days, staying in academia is really the “alternative” career for scientists. The
majority of young scientists will
not end up in a traditional academic research position. This presentation will give attendees some
criteria to consider in deciding if
embarking on an industry science
career is right for you, and then will
provide concrete tools and resources for preparing for this transition.
The third of Kamens’ presentation is “How to Choose Your Next
Lab” on Tuesday, Feb. 10, from
12:30 p.m. to 1:30 p.m., again with
the suggestion to bring a box lunch.
As for the SLAS take on this workshop: For some reasons, grad students and post-docs don’t seem to
see a lab choice as a major career
decision. Nothing could be farther
from the truth. You will spend four
to seven years working for one
person in a small group—don’t
you think this is worth a little prework to make sure it will be a good
fit and get you close to where you
want to go in the future? This presentation will give you practical
tips for what to look for and how
to find it when choosing a new lab
for your research. A must-hear for
all young scientists. n
CREDIT: NATIONAL PARK SERVICE
SLAS Career Connections
The Washington Monument celebrated its 125th anniversary in 2010. The
architectural design for the towering structure was chosen in 1836, but the
cornerstone wasn’t laid until 1848, and then the Civil War put everything on
hold—it wasn’t until the U.S. Army Corps of Engineers took over that the
structure was finally completed in 1884 and then dedicated on Feb. 21, 1885.
Networking
opportunities
for
every
lifestyle
Attendees at SLAS2015 represent “a unique nexus of diverse interests that
Receptions in the
Exhibition
of our global community.
SLAS2015 Tuesday
Night Celebration
Enjoy an out-of-this-world buffet,
select wines, domestic beers and
soft drinks
■■ Experience interstellar travel in
one of several flight simulators.
■■ Explore all museum exhibits
■■ Watch the 30-minute movie, “To
Space and Back,” in the museum’s
planetarium theater
■■ Connect with your fellow scientific
professionals
Blast Off at the Smithsonian
National Air and Space Museum
Sponsored by Hamilton Company
Tuesday, 7:00 p.m. to 10:00 p.m.
Fasten your seat belts, put your
networking goals in an upright
position and feel free to move about
the Smithsonian National Air and
Space Museum. Meet, greet and
celebrate the right stuff at one of
the Top 10 Coolest Museums in
Washington, D.C., as SLAS
continues its tradition of presenting
a memorable final evening fete to
commemorate this annual gathering
The Smithsonian National Air and
Space Museum maintains the
world’s largest and most significant
collection of aviation and space
artifacts, including the 1903 Wright
Flyer, Charles Lindbergh’s Spirit of
St. Louis, the Apollo 11 Command
Module Columbia and a lunar rock
you can touch, but not toss.
Complimentary and continuous
shuttle bus service is provided
between the Marriott Marquis and
the Smithsonian Air and Space
Museum from 6:45 p.m. to 10:15
p.m. (10 minute travel time). All
Refresh and refuel with
complimentary beer, wine, soft
drinks and snack buffets.
Sunday, 5:30 p.m.to 7:00 p.m.
Monday, 5:30 p.m.to 6:30 p.m.
Tuesday, 5:00 p.m.to 6:00 p.m.
■■
CREDIT: DESTINATION DC
fosters the limitless potential of global collaboration,” says the SLAS website,
adding, “The value of time spent in world-class educational sessions at
SLAS2015 is rivaled by time spent meeting speakers, exhibitors and other
conference participants.” The menu of social activities offers a broad array
of opportunities for attendees to get to know each other and continue
conversations that could lead—who knows?—to the next Nobel Prize.
guests must have an SLAS2015
badge and be 21 or older.
Where Everybody Knows
Your Name: The
SLAS2015 Corner Bars
Wear your SLAS2015 badge to
these nearby hot spots, then kick
back and enjoy exclusive SLAS-only
discounts on eats and drinks.
Baby Wale
10 percent off all food and drinks.
Adjacent to the Marriott Marquis,
the Baby Wale offers tasty and
creative small plates, entrees and a
complete bar menu. Location: 1124
9th St. NW (Closed Sunday, Feb. 9)
City Tap House
10 percent off all drinks. In the same
block as the Renaissance, the City
Tap House offers a full bar headlined
with craft brews from around the
world, brick-oven pizzas and elevated
pub fare (Discounts do not apply to
food). Location: 901 9th Street NW
Metrorail provides safe, clean, reliable transit service for more than 700,000
customers a day throughout the Washington, D.C. area.
On Your Mark, Get Set, Go!
Start your Monday morning with a
brisk run or walk along with your
friends from Promega and Gilson.
This 4.2 mi/6.8 km Sunrise Run
takes you past the U.S. Capitol,
Washington Monument, Lincoln
Memorial and White House.
Runners and walkers depart from
the Marriot Marquis lobby at 6:30
a.m. sharp. (The Sunrise Run
presented by Promega and Gilson is
an optional event, not an official
SLAS2015 function.)
Students and Early
Career Professionals:
Ready, Aim, Roll!
After exhibits close Sunday, students
and early-career professionals are
invited to roll over to the nearby
Lucky Strike for bowling, networking
and cajoling. Get to know others
who, like you, will drive the world’s
next wave of scientific innovation.
Enjoy glow-in-the-dark lanes, a stateof-the-art sound system and
tournament-quality billiard tables.
SLAS picks up the tab for bowling
lane rentals, bowling shoes, light
bites and soft drinks. A cash bar is
available for those 21 and older.
Home Away From Home:
The Global Village
Visitors from outside the U.S.
have a designated rendezvous point
in the SLAS2015 Exhibit Hall’s
Global Village. Meet others from
your part of the world, meet the
leaders who serve on the SLAS Asia
Council and SLAS Europe Council
and meet members of the SLAS
professional team. n
For more information, visit www.DDN-News.com
JANUARY 2015 | | DDNEWS 25
CLINICAL TRIALS
BRIEFS
Trial duration on the rise in oncology
CHICAGO—KMR Group recently reported that the
duration of oncology trials has increased steadily
within the last 10 years. The group investigated
cycle time trends for more than 4,100 oncology
trials across 32 companies, with study duration
defined as the interval from protocol approval to
database lock. Within the last decade, oncology
cycle times have risen in both Phase 2 and 3 trials;
Phase 2 oncology trials now take approximately
one year longer than trials held a decade ago,
while Phase 3 trials are taking almost five years,
one-and-a-half years longer than trials conducted
in 2003 to 2005. The increase can be attributed
partially to cancer-specific considerations, such as
increasing protocol complexity and longer treatment periods; Linda Martin of KMR Group noted
that “the enrollment and treatment processes
have expanded by almost six months each (treatment duration nearly doubled since 2003-2005).”
Traumeel-Zeel therapy provides
osteoarthritis pain relief
MANCHESTER, N.H.—A recent study has found that
co-administration of Traumeel (Tr14) and Zeel
(Ze14) intra-articular (IA) injections represents a
safe, effective treatment for moderate-to-severe
pain associated with knee osteoarthritis versus IA
placebo. The lead investigator was Dr. Carlos J.
Lozada, professor of clinical medicine, University
of Miami Miller School of Medicine. Randomized
patients with moderate-to-severe chronic knee
osteoarthritis received three weekly IA injections
of either Tr14 and Ze14 or saline, with a primary efficacy variable of change in knee pain from baseline
to end-of-study. By day 15, patients receiving the
Tr14-Ze14 combination treatment saw significant
reductions in pain, and secondary endpoints were
directionally consistent.
IN THIS SECTION
M&A activity/CNS
Otsuka to acquire Avanir
for $3.5 billion���������������������������������������� 25
Cost reduction/Engagement
On ‘cloud 9’ with
new mobile health app��������������������������� 25
Multiple sclerosis
Targeting MS at its root
(GENEURO from cover)��������������������������� 29
Oncology
Alion taps MPI
for companion diagnostic����������������������� 26
Nanomed tech shows mettle��������������������25
Pfizer, Merck KGaA pair on
immune-oncology����������������������������������� 28
Trial duration on the rise in oncology����� 25
Osteoarthritis
Traumeel-Zeel therapy provides
osteoarthritis pain relief������������������������� 25
Otsuka to acquire Avanir for $3.5 billion
Chemical entity AVP-786
for Alzheimer’s, soon to
enter Phase 3 trials, is a
major draw for Otsuka
BY JEFFREY BOULEY
TOKYO—Early December saw the announce-
ment that Otsuka Pharmaceutical Co. Ltd.
would acquire Aliso Viejo, Calif.-based Avanir
Pharmaceuticals Inc. for $17 per share in
cash, which values Avanir at approximately
$3.5 billion.
Otsuka noted that Avanir’s pipeline
includes programs in Alzheimer’s disease,
Parkinson’s disease, migraine and other
central nervous system (CNS) indications,
and made a point of highlighting a promising
new chemical entity, AVP-786, which has a
target indication for agitation associated with
Alzheimer’s disease and which is preparing
to enter Phase 3 clinical trials.
Avanir is a biopharmaceutical company
specializing in CNS diseases that was founded
in 1988. It now employs approximately 500
people and developed and launched Nuedexta (dextromethorphan hydrobromide/quinidine sulfate) capsules in the United States
As it faces patent expiry for Abilify in the United States soon, Japan-based Otsuka
Pharmaceutical is looking to buy U.S.-based Avanir for about $3.5 billion, drawn to the
biopharma in large part because of an Alzheimer’s-related drug entering Phase 3 trials and a
marketed therapy for pseudobulbar affect called Nuedexta.
in February 2011 as the world’s first and
only approved treatment for the neurologic
disease pseudobulbar affect (PBA). Sales of
Nuedexta in the 12-month period from July
2013 through June 2014 were $94 million,
a 50-percent increase over the prior-year
period, Otsuka notes.
Nuedexta, having been created to treat the
under-recognized neurologic disease PBA, is
one of “three distinct values” Otsuka cited as
On ‘cloud 9’
with new mobile
health app
Medidata, GSK evaluate impact of
cloud-based tech on engagement, data
quality and efficiencies in clinical trials
BY LORI LESKO
es linked to smartphones and cloudbased technologies
on patients in clinical trials. The method
development project
trial run with GSK
was deemed a success, Medidata
announced Nov. 6.
Furthermore, the combined
effort demonstrates the capacity
TOOLS &
TECHNOLOGY
NEW YORK—Aimed
at offering high-tech
solutions toward faster, more reliable diagnoses and treatments
in the future, life-sciences company Medidata Solutions joined hands with global
pharma giant GlaxoSmithKline
(GSK) to evaluate the impact of
mobile health (mHealth) devic-
MOBILE CONTINUED ON PAGE 27
“We were thrilled with the way the
system was able to collect and send a
huge amount of data,” notes Kara
Dennis, Medidata chief of staff, of the
joint project with GSK to evaluate the
impact of mobile health devices linked
to smartphones and cloud-based
technologies on patients in clinical trials.
reasons for acquiring the Southern California
biopharma, the second being the late-stage
investigational compound AVP-786 and the
third being Avanir’s clinical development and
commercial expertise in neurologic diseases,
which are said to complement Otsuka’s capabilities in psychiatric diseases.
“These will accelerate Otsuka’s existing
expansion strategy in the neurologic area,
AVANIR CONTINUED ON PAGE 26
Nanomed tech
shows mettle
BIND presents positive Phase 2 results
for nanomedicine platform in NSCLC at
AACR annual symposium
BY LLOYD DUNLAP
BARCELONA, Spain—BIND Therapeutics Inc., a clinical-stage
nanomedicine platform company developing targeted and programmable therapeutics called Accurins, has presented positive
results from its ongoing Phase 2
study of BIND-014 in non-small
cell lung cancer (NSCLC),
demonstrating it has met the
primary objective in the once
every three weeks (Q3W) arm
as measured by overall response
rate. The data demonstrate that
BIND-014 is well tolerated with
clinically meaningful antitu- BIND Therapeutics recently
mor activity at a lower dose presented positive results
than conventional docetaxel in from its ongoing Phase 2
patients with advanced or meta- study of BIND-014 in nonsmall cell lung cancer.
static NSCLC.
BIND-014 also demonstrates promising antitumor activity
in patients with tumors expressing KRAS mutations (mutated
Kirsten ras oncogene homolog). KRAS mutations in NSCLC
BIND CONTINUED ON PAGE 28
CLINICAL TRIALS
26 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
Alion taps MPI for companion diagnostic
Diagnostic would identify
patients likely to respond
to undisclosed ion channel
inhibitor cancer treatment
BY ZACK ANCHORS
BELMONT, Calif.—Alion Pharmaceuticals
is tapping the Medical Prognosis Institute
(MPI) to develop a companion diagnostic
that will identify patients likely to respond
to a new cancer treatment. MPI, a Danish
pharmacodiagnostic company, will devel-
“Our platform draws
on millions of data
points from diverse
groups of tumor types
to predict which
forms of cancer might
respond to a
treatment. It provides
valuable guidance in
terms of where to
direct drug
development.”
Peter Buhl Jensen,
CEO of Medical
Prognosis Institute
AVANIR
CONTINUED FROM PAGE 25
widening the overall CNS portfolio, inclusive of the psychiatric and neurologic areas,
supporting both short-and medium-term
growth,” Otsuka noted of the acquisition.
“As we bring together Otsuka’s experience and business track record in the area
of mental illnesses with Avanir’s strengths
in neurologic diseases, we believe that we
can evolve into a truly global CNS pharmaceutical company,” according to Taro
Iwamoto, Otsuka’s president and representative director. “Avanir’s creativity and
proven execution on drug discovery and
development for largely unexplored medical indications, typified by PBA, represents
a hand-in-glove fit with Otsuka’s culture.
We admire and respect Avanir’s innovative
vision and execution and want to continue
to grow together.”
Though not yet an approved and marketed
op a predictive test
that will help Alion
select patients for
clinical trials of one
of several ion channel inhibitors the
firm is developing
for the treatment of certain cancers. Alion
has not disclosed which of its ion channel inhibitors MPI’s diagnostic test will be
geared toward.
MPI, which has an office in Scottsdale,
Ariz., develops companion diagnostics to
support the development of cancer therapeutics. Its DRP platform is used by drug
development teams to identify which
patients will respond to a drug and which
indications of the drug are most likely to
be most successful. The platform, which
combines gene expression profiling with
systems biology analytics, has the potential
to significantly increase the probability of
successful Phase 3 drug development. MPI
reports the DRP can be used in all cancer
types and was patented for more than 60
anticancer drugs in the United States in
2013.
“Our platform draws on millions of data
points from diverse groups of tumor types to
predict which forms of cancer might respond
to a treatment,” Peter Buhl Jensen, CEO of
MPI, tells DDNews. “It provides valuable
guidance in terms of where to direct drug
development.”
Alion is a pharmaceutical company
focused on developing a pipeline of ion
channel inhibitors and integral membrane
proteins to treat cancer and central nervous
TOOLS &
TECHNOLOGY
therapeutic, AVP-786 is a strong draw, Iwamoto has noted, because as many as half of
patients with Alzheimer’s disease experience
agitation, which can manifest as verbal abuse,
confusion and aggression. Dementia-related
behavioral symptoms, agitation among them,
not only make the disease more distressing
to the people suffering from it, but they also
increase burdens on family and other caregivers—these behavioral disturbances also have
been associated with more rapid cognitive
decline and institutionalization.
Avanir has continued to advance a clinical program for the treatment of agitation
in Alzheimer’s disease, a complication which
currently lacks any effective and safe treatment, Otsuka notes. Avanir presented Phase
2 proof-of-concept trial results at the American Neurological Association annual meeting
in October 2014, and the company expects to
meet with the U.S. Food and Drug Administration in early 2015 to discuss advancement
of the program.
“Avanir’s creativity and proven execution on drug
discovery and development for largely unexplored
medical indications, typified by PBA, represents a
hand-in-glove fit with Otsuka’s culture. We admire
and respect Avanir’s innovative vision and
execution and want to continue to grow together.”
Taro Iwamoto, president and representative
director of Otsuka
“This project underscores Alion’s commitment
to the development of precision cancer drugs
by employing cutting-edge companion
diagnostics to identify and enroll the right
patients in order to conduct successful clinical
trials with patients that will actually benefit.”
Allan Bates, CEO of Alion
system disorders. Ion channels regulate
specific stages of cancer, and researchers
have found that blocking activity in ion
channels can impair the growth of some
tumors. Alion’s proprietary techniques can
be used to identify small molecules that
modulate specific ligand and voltage-gated
ion channels.
Alion will use MPI’s drug predictor platform to identify which general types of cancers its ion channel inhibitor has the most
potential to treat effectively. DRP may then
be used to select and enroll likely responder
patients in a Phase 1 trial for the drug.
“This project underscores Alion’s commitment to the development of precision cancer
drugs by employing cutting-edge companion
diagnostics to identify and enroll the right
patients in order to conduct successful clinical trials with patients that will actually benefit,” said Alion CEO Allan Bates.
MPI co-founder and Chief Scientific Officer Steen Knudsen said that he is “confident
that the DRP biomarker to be developed
for Alion’s lead ion channel inhibitor will
enable the identification and selection of
Otsuka and Avanir are looking to pair the
former’s strengths in mental illness
therapeutics with the latter’s expertise in
neurologic treatments.
Otuska has also cited its respect for
Avanir’s “creativity and proof through execution” with regard to Nuedexta, noting that
Avanir successfully took on the challenge to
create, develop and commercialize a drug in a
new disease category for which no approved
treatment existed, an approach and level of
creativity described as “remarkably consistent with Otsuka’s.”
“I am extremely excited to see these two
organizations come together to create a leading CNS company. Otsuka is a clear leader in
psychiatry and Avanir in neurology; together, I believe our organizations will be able
to more rapidly develop and commercialize
needed medications to potentially help millions of patients around the world,” said Keith
A. Katkin, president and CEO of Avanir.
He and his company also noted in their
news release about the acquisition that Otsuka “has created numerous innovation seeds
through its horizontal alliances in the CNS
field with other companies: Lundbeck and
likely responding patients for the drug, and
we look forward to confirming this as the
Phase 1 trial unfolds.”
Jensen tells DDNews that the agreement
demonstrates the potential of its diagnostic
platform to steamline and improve the drug
development process while minimizing
risks. “Partnerships like this provide MPI
another chance to demonstrate proof of concept in screening patients,” he notes. “Working with Alion will allow us to advance a
new paradigm in cancer drug development
by using our diagnostic platform to select a
targeted population of patients most likely
to respond to this drug based on their tumor
biology.” Jensen also adds that while large
pharmaceutical companies have developed
their own diagnostic systems, few have been
as thoroughly tested as MPI’s. “ I think that
our platform has real value for Big Pharma
companies because it is a system that has
been validated thoroughly,” he says.
Financial terms of the agreement between
Alion and MPI have not been publicly disclosed. n
EDITCONNECT: E011519
BMS on psychiatric therapies, and IBM and
Proteus Digital Health on digital solutions for
patients, their families, healthcare providers
and other caregivers.”
The timing of the Avanir deal, some market watchers suggest, may have a lot to do
with heading off a tumble over the edge of
a patent cliff in April 2015, when Otsuka’s
U.S. patent for the drug Abilify—used to
treat schizophrenia, bipolar disorder and
depression—expires and the company has
to face generic competition. Avanir offers at
least one path toward bolstering the pipeline
with patent-protected products. Otsuka also
bought U.S.-based oncology therapeutics
company Astex Pharmaceuticals Inc. in 2013
for about $886 million, presumably also in
part to beef up the pipeline before Abilify
lost patent protection.
The acquisition has been unanimously
approved by the boards of directors of both
companies. The closing of the tender offer
will be subject to the tender of a majority
of Avanir’s shares outstanding and certain
other customary closing conditions, including expiration or termination of the waiting
period under the Hart-Scott-Rodino Antitrust Improvements Act. The transaction is
expected to close in the first quarter of 2015.
Upon close of the transaction, Avanir will
continue to operate under its current structure as an independent subsidiary of Otsuka
America Inc. Avanir will partner with Otsuka
in the United States to further enhance its
development and commercialization efforts
in CNS-related disorders. n
EDITCONNECT: E011516
MOBILE
CONTINUED FROM PAGE 25
for technology to accelerate innovation in
drug development and makes a strong case
for cross-industry collaboration between
technology and life sciences, Medidata stated.
The joint pilot project was administered at
GSK’s Human Performance Lab where, over
a five-day period, six participants wore two
devices: the Vital Connect’s HealthPatch MD,
placed on the chest, and ActiGraph’s wGT3XBT Monitor, placed on the wrist. The devices
continuously measured vital signs, electrocardiogram data and activity levels. Such devices
can also potentially monitor stress levels, diabetes signs, sleep patterns and more.
A mobile app on a smartphone, given to
all participants, was read by the Medidata
Patient Cloud, for patient-reported outcomes
offered as part of Medidata’s technology platform. The Medidata Clinical Cloud captured
all the data, mapping mobile health data to
CLINICAL TRIALS
of secure and analysis-ready data.
Medidata intends to use the technology
infrastructure developed for this initiative
as a model to enable new Phase 1 through
Phase 4 mHealth clinical trials, which the
company will be supporting for clients over
the coming months.
The collaborative project with GSK demonstrated that mHealth technologies have
the power to comprehensively collect large
volumes of objective data that is reliable,
secure and analysis-ready and that provides
real-time, continuous insight into the wellbeing of patients, according to the company.
Medidata collected more than 18 million
data points on activity and vital signs per participant per day. All of the data collected was
audited and is compliant with FDA regulations. Additionally, the effort indicated that
mobile devices can support the long-term
goal of lessening the burden on patients participating in studies by streamlining routine
procedures, eliminating unnecessary ones
“Working with GSK on this initiative has provided us
with an exciting opportunity to show how technology can
be used to enhance patient engagement and accelerate
the pace of innovation in drug development. We gathered
data on an unprecedented scale. This is an extraordinary
level of in-life, real-time patient instrumentation for
clinical trials, which will create new disciplines and new
opportunities for life-science companies.”
Glen de Vries, president of Medidata
the clinical record.
Speaking on the collaboration with GSK,
Kara Dennis, Medidata chief of staff, tells
DDNews: “We were thrilled with the way the
system was able to collect and send a huge
amount of data.”
As chief of staff, Dennis oversees Medidata’s priority strategic initiatives to advance
clinical trials and accelerate internal efforts.
Medidata’s cloud-based program has “tremendous potential for providing a better
level of insight in clinical studies than ever
before, tracking the progression of diseases
and being an accurate predictor of adverse
events,” Dennis says. Medidata’s program is “a
very promising, very important development
in clinical research.”
“We plan to pursue follow-up trials,” Dennis adds. “There is still work to be done.”
Pairing mobile health and cloud-based
technologies streamlines the data collection, management and analysis process, as
well as reduces site visits. Other key benefits
of combining these technologies include
streamlined routine procedures and realtime, continuous insight into large volumes
and reducing visits to clinical trial sites.
“Working with GSK on this initiative has
provided us with an exciting opportunity to
show how technology can be used to enhance
patient engagement and accelerate the pace
of innovation in drug development,” said Glen
de Vries, Medidata’s president. “We gathered
data on an unprecedented scale. This is an
extraordinary level of in-life, real-time patient
instrumentation for clinical trials, which will
JANUARY 2015 | | DDNEWS 27
CREDIT: MEDIDATA
For more information, visit www.DDN-News.com
A mobile app on a smartphone is read by the Medidata Patient Cloud for patient-reported
outcomes offered as part of Medidata’s technology platform.
breakthroughs over time will help to alleviate
any concerns about regulatory compliance
and data quality, much like the early days of
the Internet and electronic data capture.”
Medidata is a global provider of cloud-based
solutions for clinical research in life sciences,
aiming to transform clinical development
through its advanced applications and intelligent data analytics. The Medidata Clinical
Cloud is intended to increase productivity and
quality for the clinical testing of medical treatments, from study design and planning through
execution, management and reporting.
Vital Connect is a Silicon Valley-based
company founded in 2011 with the goal of
developing the newest generation of technologies that help address some of the most
challenging healthcare issues in the world
today. Vital Connect creates wireless, wearable biosensors that are small, powerful and
capable of capturing clinical-grade biometric
measurements in a continuous, configurable
and unobtrusive manner. n
create new disciplines and new opportunities
for life-science companies.”
“Seamlessly integrating data from HealthPatch MD into clinical records through the
Medidata Clinical Cloud opens up new possibilities to measure biometrics from heart
rate to skin temperature,” added Dr. Nersi
Nazari, Vital Connect’s chairman and CEO.
“The availability of continuous, clinical-grade
health data provides important opportunities to analyze results in real time to quickly
identify potential safety concerns and adjust
a trial based on preliminary evidence.”
Medidata’s data science team is working
with GSK to leverage the data from the project and turn it into insight that can be used
to conduct faster and more patient-centric
clinical research.
“When it comes to mHealth, there is one
aspect everyone agrees on: the technology is
here now,” de Vries stated. “Breakthroughs in
mHealth adoption can come from clear demonstrations of using mobile devices in a compliant, effective and safe way. We believe these
EDITCONNECT: E011517
APRIL 18-22, 2015
PENNSYLVANIA CONVENTION CENTER
PHILADELPHIA, PA
Join us in Philadelphia
for the most comprehensive
cancer research meeting in the world...
the AACR Annual Meeting 2015!
Connect with the international cancer research community to foster new
collaborations, learn about cutting-edge advances, and obtain feedback on
your research. This must-attend meeting covers every aspect of cancer – from
epidemiology, molecular biology, and clinical studies to prevention, survivorship,
and patient advocacy.
The Vital Connect’s HealthPatch MD is
placed on the chest to measure vital signs,
electrocardiogram data and
activity levels.
Register Today!
1409109J_15AM_ad_DDNews_7x4.875_1.indd 1
We look forward
to welcoming you
to our hometown of
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CLINICAL TRIALS
28 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
Pfizer, Merck KGaA pair on immune-oncology
Potential $2-billion deal
aimed at developing
and commercializing
investigational antiPD-L1 antibody
NEW YORK—Pfizer Inc. announced
Nov. 17 that it had entered into an
agreement with Germany’s Merck
KGaA (which is not affiliated
with U.S.-based Merck & Co.) to
jointly develop and commercialize
MSB0010718C, an investigational
anti-PD-L1 antibody currently in
development by Merck KGaA as a
potential treatment for multiple types
of cancer. The companies will explore
the therapeutic potential of this novel
anti-PD-L1 antibody as a single agent
as well as in various combinations
with Pfizer’s and Merck KGaA’s broad
portfolio of approved and investigational oncology therapies.
Under the terms of the agreement, Merck KGaA will receive an
upfront payment of $850 million
and is eligible to receive regulatory and commercial milestone
payments up to approximately $2
billion. Both companies will jointly
fund all development and commercialization costs, and all revenues
BIND
CONTINUED FROM PAGE 25
are generally associated with poor
response to currently available
drug therapy regimens, including
docetaxel. An additional signal was
observed in patients with squamous
cell carcinomas, a major NSCLC
subtype poorly served by existing
available therapies.
These data were presented at the
26th EORTC-NCI-AACR Symposium
on Molecular Targets and Cancer
Therapeutics in Barcelona, Spain.
“We believe the activity and tolerability of BIND-014 demonstrated
in this study suggest meaningful
differentiation from the historical
docetaxel experience, in both the
broader NSCLC patient population and in two important groups of
patients with high unmet medical
need,” said Dr. Hagop Youssoufian,
BIND’s chief medical officer. “Furthermore, as the first product candidate from our Medicinal Nanoengineering platform to enter the clinic,
we believe that the increased efficacy
and reduced toxicity at a lower dose
compared to historical docetaxel
experience suggests that Accurins
are successful in targeting the therapeutic payload to the tumor. Based
on these positive results, we plan
to conduct additional global, multicenter Phase 2 studies to confirm
and expand the dataset on BIND-014
and to define an expeditious regulatory path for BIND-014.”
“Data from this open-label study
suggest the potential for BIND014 superiority over docetaxel in
Merck KGaA (pictured here) and Pfizer will explore the therapeutic potential
of MSB0010718C, a novel anti-PD-L1 antibody, as a single agent as well as
in various combinations with both companies’ oncology therapies.
obtained from selling any anti-PDL1 or anti-PD-1 products generated from this collaboration will be
shared equally.
The pair will be building on an
ongoing Phase 1 program that has
treated more than 550 patients, and
they will collaborate on up to 20
high-priority immuno-oncology
clinical development programs
expected to commence in 2015.
These clinical development programs include up to six trials in
Phase 2 or 3 that could be pivotal
for potential product registrations.
“This global alliance enables
the treatment of NSCLC patients,”
said Dr. Ronald B. Natale, medical
director of the Clinical Lung Cancer Program at the Women’s Guild
Lung Institute and investigator for
the Phase 2 trial of BIND-014 in
NSCLC. “Furthermore, BIND-014
demonstrated intriguing activity in
patients with KRAS-mutated lung
cancers, a group of patients who
have historically been unresponsive to standard treatment with
docetaxel. This initial experience
with BIND-014 provides a glimpse
into a new way to selectively target
NSCLC tumors, an area of cancer
with high unmet need.”
BIND plans to initiate global,
multicenter Phase 2 studies of
BIND-014 in patients with KRAS
mutant NSCLC and in patients
with NSCLC of squamous histology who have progressed on prior
therapy. These studies aim to assess
overall survival and additional endpoints to position BIND-014 for
subsequent registration studies.
The Q3W dosing arm of the
open-label, multicenter, Phase
2 study discussed in Barcelona enrolled 40 patients with
advanced metastatic NSCLC who
were treated with 60 mg/m2 of
BIND-014 on day one of a 21-day
cycle· Five patients (13 percent)
achieved a partial response with a
median duration of response of 5.2
months and median progressionfree survival (PFS) of 2.7 months.
There was one unconfirmed partial
response that was not included in
the analysis per RECIST v1.1. Nine
patients were enrolled with a con-
Pfizer and Merck KGaA to join
forces and combine complementary
strengths with the goal of meeting
the needs of patients with multiple
types of cancer,” said Albert Bourla,
group president of Pfizer’s Vaccines,
Oncology and Consumer Healthcare
Businesses. “Immuno-oncology is a
top priority for Pfizer. Combining
this promising anti-PD-L1 antibody
with Pfizer’s extensive portfolio of
small molecules and antibodies provides an opportunity to potentially
broaden the use of immunotherapy
for patients with cancer and rapidly expand our oncology business.
In addition, this alliance enables us
to significantly accelerate the timeframe of our development programs
and move into the first wave of
potential immuno-oncology-based
treatment regimens.”
“Collaborating globally with Pfizer will allow us to benefit from the
strengths and capabilities of both
companies in immuno-oncology,
further accelerating this promising
asset in the race to address the needs
of cancer patients across multiple
tumor types,” added Belén Garijo,
president and CEO of Merck’s biopharmaceutical division, Merck
Serono. “On top of that, the global
alliance will enable Merck to gain
an early entry into the U.S. oncology
market as well as to strengthen our
existing oncology business in several other important global markets.”
According to Dr. Mikael Dolsten, president of Pfizer Worldwide
Research and Development, “Early
results for Merck KGaA’s PD-L1 in
patient trials are impressive and
consistent with the results seen
with the class of PD-1 and PD-L1
antibodies. This promising foundation of research will form the basis
of multiple registration trials.”
Separate from the PD-L1 pro-
Nanomedicine and nanotechnology in general are an increasingly active
segment in life-sciences overall and therapeutics specifically. BIND
Therapeutics, for one, is a clinical-stage nanomedicine platform company
developing targeted and programmable therapeutics called Accurins.
firmed KRAS mutation, and two of
those nine experienced an objective response (22 percent); median
PFS in patients with KRAS mutant
tumors was 2.7 months.
In patients with squamous cell
carcinoma there were no confirmed objective responses; however, median PFS in patients with
squamous cell carcinoma was 2.8
months. Prolonged (more than four
cycles) disease control was also
noted in six of nine (66 percent)
patients with squamous histology.
Preliminary median overall survival was 6.2 months for all patients
treated, 9.6 months in patients
with KRAS mutant tumors and 11.1
months in patients with squamous
cell carcinoma.
Twenty-one of 40 patients
received four or more cycles of
therapy, attesting to the tolerability
of BIND-014. Consistent with previous results, neutropenia, anemia,
neuropathy and alopecia, commonly observed with docetaxel, were significantly reduced with BIND-014.
Based on the promising results
of the Q3W arm and the more
patient-friendly once every three
weeks dosing schedule, combined
grams, Pfizer and Merck KGaA will
also combine resources and expertise to advance Pfizer’s anti-PD-1
antibody into Phase 1 trials. The parties have also agreed to co-promote
Pfizer’s Xalkori in the United States
and several other key markets.
Zacks Investment Research analysts wrote that they are “encouraged” by the collaboration and
added that the agreement should
help Merck KGaA’s Merck Serono
division to remain on track with its
“Fit for 2018” program, which was
initiated in 2011. The Zacks investor note also cited that in June 2014,
Merck KGaA signed an agreement
with MorphoSys AG for discovery
and development work related to
therapeutic antibodies against undisclosed immune checkpoints.
“We believe that the agreement
with Pfizer will leverage Merck
KGaA’s immuno-oncology pipeline and accelerate the timelines
involved with the development
programs. Moreover, this alliance
should facilitate Merck KGaA’s
entry into the U.S. oncology market
apart from boosting the company’s
existing oncology business in other
markets,” noted Zacks in its analysis. n
with the absence of a confirmed partial response in the first 22 patients
enrolled on the Q1W schedule, the
company will not continue enrollment on the weekly dosing schedule.
BIND-014, a targeted polymeric
nanoparticle, represents the first
Accurin nanomedicine from BIND’s
Medicinal Nanoengineering platform to reach the clinic. BIND014 targets prostate-specific membrane antigen, a target expressed
on prostate cancer cells and the
blood vessels of many types of nonprostate solid tumors, and contains
docetaxel, a clinically validated and
widely used anticancer agent. In
preclinical cancer models, BIND014 was shown to increase accumulation of docetaxel at the site of
disease, which translated to marked
improvements in antitumor activity
and tolerability. In clinical studies
conducted to date, BIND-014 has
been shown to be generally welltolerated and displayed antitumor
activity at low doses and in tumors
where conventional docetaxel has
minimal activity.
Accurins are BIND’s targeted
and programmable therapeutics, which are designed utilizing
BIND’s medicinal nanoengineering
platform. BIND has demonstrated
in preclinical studies that Accurins
can improve tumor growth suppression, achieve higher concentrations of the payload in tumors
compared to conventional delivery,
and have pharmacokinetics and tolerability differentiated from their
therapeutic payloads. n
EDITCONNECT: E011518
CLINICAL TRIALS
For more information, visit www.DDN-News.com
GENEURO
CONTINUED FROM PAGE 1
addition to royalties on future
sales. Servier will also have the
option to take an equity stake in
GeNeuro as a minority shareholder
in the next 12 months.
“This agreement is an ideal way to
develop GeNeuro’s technology and
deliver its full value for patients and
stakeholders,” says Jesús MartinGarcia, GeNeuro’s chairman. “With
all further development costs in MS
funded by our partner, GeNeuro has
a clear path forward with a manageable geographic focus on two of the
world’s major markets.”
Unlike current treatments for
MS, which focus on reducing the
frequency of relapses, GeNeuro’s
drug holds the potential to stop
progression of the disease altogether. Most current treatments target
the patient’s immune system, an
approach that has limited effectiveness at slowing the progress
of the disease and that can leave
patients with an increased risk of
infections and cancers. GNbAC1
instead targets MSRV-ENv, a protein that appears to be closely tied
to the root causes of the disorder.
MSRV-ENv is expressed in all
active lesions of MS patients, and
it both induces inflammation and
blocks the remyelination process,
which provides a protective mechanism for neurons. “Targeting this
causal factor has the potential to
stop disease progression,” Curtin
says. “By blocking the MSRV-ENv
target, the drug could act on the
inflammatory and neurodegenerative components of all forms
of MS.”
GNbAC1 could also be particularly well suited to treat the progressive forms of MS for which
there is currently no approved
treatment. About 40 percent of MS
patients experience these forms of
the disease, which are characterized by symptoms worsening over
time. Current treatments only
address the relapsing-remitting
forms of MS.
GeNeuro’s initial studies of
GNbAC1 have revealed an attractive safety profile. An open-label
extension of a Phase 2a safety study
in 10 MS patients resulted in stability of brain lesions by MRI from
baseline to 12 months, overall clinical stability and no signs of immunogenicity. Researchers also found
a statistically significant decline of
MSRV biomarkers in the blood during treatment. “This study, as well
as a Phase 1 study in healthy individuals, showed that GNbAC1 was
safe,” says Curtin. “These results
are very promising.”
The Phase 2b trial of GNbAC1
that will be funded by Servier is
expected to begin by the middle of
2015 and produce data by the end
of 2017. This trial will involve 200
to 250 patients with a relapsingremitting form of MS.
The global market for MS treat-
ments currently sees $12 billion
to $13 billion in annual sales, and
GeNeuro estimates it will increase
by 50 percent in the next 10 years.
Although there is substantial competition, GNbAC1’s potential efficacy for progressive forms of MS
and its attractive safety profile
could help it stand out. “There is
still a large unmet medical need
and ample space for innovative
treatments acting on the progression of the disease and allowing
safe, long-term treatment,” explains
JANUARY 2015 | | DDNEWS 29
“This agreement is an ideal way to develop GeNeuro’s
technology and deliver its full value for patients and
stakeholders. With all further development costs in
MS funded by our partner, GeNeuro has a clear path
forward with a manageable geographic focus on two
of the world’s major markets.”
Jesús Martin-Garcia, GeNeuro chairman
Curtin. “GNbAC1 should fulfill
these requirements.”
GeNeuro was created in 2006
at Eclosion, the Geneva life-sci-
ences accelerator, as a spin-off of
Institut Mérieux. The company is
primarily focused on the development of GNbAC1 as a treatment
for MS. Olivier Laureau, president
of Servier, says GeNuero makes
an especially well-suited partner
for his company. “Not only will
this new strategic alliance allow
Servier to enrich its portfolio in a
disease with a huge unmet medical
need, but we are especially proud
to count as partner a company that
was spun off from Institut Mérieux,
a French institution internationally recognized for its excellence
in research.” n
EDITCONNECT: E011501
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!
30 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
DIAGNOSTICS
Illumina, Sequenom
resolve patent disputes
SAN DIEGO—Illumina Inc. and Sequenom Inc. have
reached an agreement that will settle all pending
infringement claims and other disputes between
Sequenom and Verinata Health Inc. The companies
will pool the intellectual property directed to noninvasive prenatal testing (NIPT) they own and have
in-licensed, including patents that remain the focus
of ongoing interference proceedings. Per the agreement, Illumina will have exclusive worldwide rights to
use the pooled IP to develop and sell in-vitro diagnostic kits for NIPT and license third-party labs that want
to develop and market their own NIPT tests under the
pooled patents. Sequenom and Illumina both have
rights to use all pooled patents to develop and sell
their own NIPT and will share revenue from the patent pool, with Illumina paying Sequenom a royalty
on sales of in-vitro diagnostic kits for NIPT. Illumina
will pay Sequenom $50 million up front, as well as
ongoing commitments for payments to Sequenom
from the patent pool structure through 2020.
Investments support
Sequenta MRD test
SOUTH SAN FRANCISCO, Calif.—Sequenta Inc. has
announced that Celgene Corp. and others have
made equity investments in the company. The
funding will support Sequenta’s incorporation
of the ClonoSIGHT minimal residual disease
(MRD) test into clinical trials of medicines being
developed for various blood cancers as well as
development of clinical diagnostics based on the
company’s LymphoSIGHT platform.
“Celgene’s investment in Sequenta, along with
the other strategic investors, will further support
adoption of our powerful minimal residual disease
detection and quantification technology as the
emerging standard for response assessment and
disease monitoring in clinical trials of medicines
for blood cancers, as well as the development of
new applications of our LymphoSIGHT platform,”
said Tom Willis, CEO of Sequenta.
IN THIS SECTION
Antibiotics
A good attitude toward Longitude.......... 30
Litigation/Patents
Illumina, Sequenom
resolve patent disputes........................... 30
M&A activity/Prenatal/
DNA testing
A harmonious transaction....................... 30
Oncology
Investments support
Sequenta MRD test................................. 30
myChoice CDx becomes
TESARO’s choice..................................... 32
Rheumatology/Arthritis
Achieving good arthritis predictions....... 31
A good attitude toward Longitude
CPA Global to support
Longitude Prize 2014,
which seeks to improve
the antibiotic landscape
BY KELSEY KAUSTINEN
ALEXANDRIA, Va.—Antibiotic resistance rep-
resents a global challenge, and in the United
Kingdom, that issue is the target of Longitude
Prize 2014, an international challenge with
the goal of finding a fast, accurate, easy-to-use
and cost-effective test for bacterial infections,
which will allow health professionals to give
patients the right antibiotics at the right time.
And stepping up to support this initiative
is CPA Global, which provides intellectual
property management services and software.
CPA Global’s support comes in the form of
a detailed patent landscape study, which the
company will undertake through Landon IP,
its specialist patent research subsidiary. The
results will provide the Longitude Prize judging panel with a benchmark against which it
can compare submissions in terms of originality and claimed speed, accuracy and ease
of use. The study will also indicate the types
of organizations active in this arena and what
A portrait of Alexander Fleming, who discovered penicillin, created by celebrity portrait artist
Nathan Wyburn using 25,800 capsules. The work was commissioned to mark the opening of the
2014 Longitude Prize.
biotics are needed and, if they are, which ones
to use. This is vitally important as the incorrect
use and overuse of antibiotics is a major con-
countries they hail from.
“We are proud to be supporting Longitude
Prize 2014 and the search for a transformative
point-of-care test that will identify when anti-
PRIZE CONTINUED ON PAGE 31
A harmonious transaction
Roche acquires Ariosa
Diagnostics, gains
noninvasive Harmony
Prenatal Test
BY KELSEY KAUSTINEN
BASEL, Switzerland—Roche capped off 2014
by expanding its testing services footprint
with the acquisition of privately held Ariosa
Diagnostics Inc., a molecular diagnostics
testing service provider that offers a highly
targeted and accurate noninvasive prenatal testing (NIPT) service through its CLIA
laboratory. Though no financial details were
disclosed, the transaction was expected to
close in December 2014.
Ariosa’s portfolio features its proprietary
Harmony Prenatal Test, a blood test performed as early as 10 weeks into pregnancy
to assess a fetus’ risk of Down syndrome and
other genetic abnormalities. The test evaluates fetal cell-free DNA found in maternal
blood and specifically determines the risk of
trisomies 13, 18 and 21, which indicate an
extra chromosome in the fetus that could
result in severe genetic conditions. The test
has been validated to CLIA requirements and
supported by clinical studies in more than
CREDIT: ARIOSA DIAGNOSTICS
BRIEFS
“Cell-free DNA technology allows one to have
a direct view into the assessment and
monitoring of disease through a simple
standard blood draw. This can avoid invasive
testing, which often carries with it cost and
complications,” says Dr. Ken Song, CEO of
Ariosa Diagnostics.
22,000 women, and reportedly has a falsepositive result of less than 0.1 percent.
“The noninvasive prenatal testing market
with cell-free DNA has represented one of
the fastest-growing segments in the diagnostics industry,” says Dr. Ken Song, CEO of
Ariosa. “For Ariosa’s Harmony Prenatal Test,
testing volume has grown from approximately 30,000 women in 2012 to over 200,000
women in 2014. Penetration of the NIPT
market is still in its infancy, as the use of
NIPT in the global general pregnancy population is just beginning to emerge.”
While the companies haven’t worked
together before, both were impressed with
each other. Dan Zabrowski, head of Roche
Tissue Diagnostics and Roche Sequencing
Unit, reports that upon deciding to enter the
NIPT market, Roche identified Ariosa as the
best partner. For his part, Song says “Roche’s
global leadership in in-vitro diagnostics and
their focus on innovation made them a natural partner for Ariosa, especially as we look
to broaden access for the Harmony Prenatal
Test via a kit strategy.”
“We’re seeing a paradigm shift in prenatal
screening towards noninvasive cell-free DNA
technology where we can identify the risk of
aneuploidies with a high degree of accuracy
over traditional screening methods,” Song
adds. “Cell-free DNA technology allows one
to have a direct view into the assessment
and monitoring of disease through a simple
NIPT CONTINUED ON PAGE 32
For more information, visit www.DDN-News.com
DIAGNOSTICS
JANUARY 2015 | | DDNEWS 31
Crescendo’s Vectra DA is
a better predictor of joint
damage in RA patients
BY LLOYD DUNLAP
SALT LAKE CITY—Crescendo Bioscience, a
wholly owned subsidiary of Myriad Genetics
Inc., has presented new data that show Vectra
DA is a better predictor of radiographic progression over two years than other tests used to
assess the risk of joint damage in rheumatoid
arthritis (RA), such as C-reactive protein (CRP).
The oral presentation was featured at the 2014
American College of Rheumatology (ACR)
Annual Meeting in Boston. Myriad acquired
Crescendo in Feb. 2014 as part of its three-part
growth strategy focused on oncology, a diversified product portfolio and expansion internationally, notes Ron Rogers, Myriad’s executive
vice president of corporate communications.
The study included 143 patients with RA
who had received a stable treatment and were
enrolled in the Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS)
“In this study of U.S.
patients, Vectra DA was a
strong predictor of joint
damage over two years,
compared with other tests.
These data build on prior
studies demonstrating that
Vectra DA can assess risk for
joint damage and
complement other measures
of disease activity.”
Dr. Eric Sasso, vice president
of medical and scientific affairs
at Crescendo Bioscience
PRIZE
CONTINUED FROM PAGE 30
tributor to the rise of antibiotic resistance. We
hope that the Longitude Prize challenge will
be a catalyst for further—and urgent—innovation in developing solutions that address this
major worldwide problem,” CPA Global’s CEO,
Tim Griffiths, said in a press release.
The Longitude Prize, which is run by Nesta
and supported by Innovate UK (the new
name for the Technology Strategy Board) as
a funding partner, began accepting entries
on Nov. 18. Competitors for the Longitude
Prize have up to five years to find a solution, and regular submission deadlines have
been established, after which entries will be
reviewed, with potential winning solutions
submitted to the Longitude Committee. The
Committee can select the winner at any point
during the five-year period of the challenge,
and the Longitude Prize website lists Dec. 31,
2019, as the closing date.
Longitude Prize 2014 has a £10 million
(approximately $15.6 million) prize fund.
British Prime Minister David Cameron
announced the initiative at G8 2013. The
Prize commemorates the 300th anniversary
of the Longitude Act of 1714, in which Britain’s government challenged scientists to find
registry in the United States. Patients were
evaluated at their initial visit in the BRASS
registry for the Vectra DA score and conventional measures of disease activity, including
CRP, DAS28-CRP, CDAI, SDAI and RAPID3,
and provided X-rays of hands and wrists at
approximately the initial visit and two years
later. These data were used to assess the
relationship between disease activity and
the amount of subsequent new joint damage
seen on X-rays (radiographic progression).
Results showed that Vectra DA was the best
independent predictor of disease progression
over two years compared with standard measures based on the exam or patient-reported
outcome. The odds ratio for predicting progression was highest for Vectra DA and lowest
for RAPID3. Among patients with a low CRP
at baseline, defined as <1 mg/dL, radiographic
progression was observed in 34.8 percent of
patients with a high Vectra DA score versus 8.1
percent of patients with a low/moderate Vectra DA score, providing further evidence that
Vectra DA provides information for predicting
joint damage that is not provided by CRP.
“In this study of U.S. patients, Vectra DA
was a strong predictor of joint damage over
two years, compared with other tests,” said Dr.
Eric Sasso, vice president of medical and scientific affairs at Crescendo Bioscience. “These
data build on prior studies demonstrating that
Vectra DA can assess risk for joint damage and
complement other measures of disease activity.” Sasso notes that a low score (less than
30) would indicate low, infrequent damage,
where a moderate score of between 30 and 44
on the continuum and 44 or higher indicated
a heightened risk profile.
Another study featured at ACR provided
an analysis of radiographic progression in
patients with early RA from the Swedish
Farmacotherapy (SWEFOT) clinical trial.
The Vectra DA test was used to evaluate 220
patients for progression from baseline to
year one and from baseline to year two. In
addition, progression from year one to year
CREDIT: MYRIAD GENETICS
Achieving
good
arthritis
predictions
New clinical data show
Myriad acquired Crescendo in Feb. 2014 as
part of its three-part growth strategy focused
on oncology, a diversified product portfolio
and expansion internationally, notes Ron
Rogers, Myriad’s executive vice president of
corporate communications.
two was evaluated for 133 patients who had
inadequate initial responses to methotrexate and were treated from month three with
the addition of a TNF inhibitor or with triple
therapy using methotrexate, sulfasalazine
and hydroxychloroquine.
Among patients with a high Vectra DA
score at baseline, 25 percent of those with a
high Vectra DA score at month three showed
rapid radiographic progression during the
first year, and 35 percent of those with a high
Vectra DA score at one year showed rapid
radiographic progression between year one
to year two. By contrast, for patients whose
high baseline Vectra DA score declined to
low after three months or one year of treatment, only 6 percent and 4 percent showed
rapid radiographic progression between year
one to year two. Moreover, for patients who
had a moderate Vectra DA score at baseline
and achieved a low Vectra DA score at three
months, none showed rapid radiographic
progression during the first year.
“In this study, a high Vectra DA score was
associated with markedly increased risk for
joint damage, and a low Vectra DA score was
associated with low risk for subsequent joint
damage,” said Sasso. “These findings suggest
how Vectra DA may be used to objectively
assess disease activity following initiation of
therapy to help manage the patient’s disease.”
Vectra DA is reportedly the only multibiomarker blood test for RA disease activity that
integrates the concentrations of 12 serum proteins associated with RA disease activity into
a single objective score, on a scale of one to
100, to help physicians make more informed
treatment decisions. Vectra DA testing is performed at the Crescendo Bioscience CLIAcertified facility, and test results are reported
to the physician five to seven days from shipping of the specimen to Crescendo. Physicians
can receive test results via standard mail, by
fax or via the private web portal, VectraView.
Crescendo Bioscience, located in South San
Francisco, Calif., is a molecular diagnostics
company dedicated to developing and commercializing quantitative blood tests for RA
and other autoimmune diseases. Crescendo
Bioscience develops quantitative, objective,
reproducible blood tests to provide rheumatologists with deeper clinical insight to help
enable more effective management of patients
with autoimmune and inflammatory diseases.
In other news, parent company Myriad
Genetics recently announced that it has
received approval from the U.S. Food and Drug
Administration (FDA) for BRACAnalysis CDx
to be used as the only companion diagnostic
in conjunction with AstraZeneca’s Lynparza
(olaparib). Lynparza is the first poly ADP-ribose
polymerase (PARP) inhibitor for patients with
germline mutations in BRCA1/2 advanced
ovarian cancer who have had three or more
lines of chemotherapy. BRACAnalysis CDx is
Myriad’s first FDA-approved companion diagnostic for use with a novel PARP inhibitor. n
EDITCONNECT: E011522
“We are proud to be supporting Longitude Prize 2014 and the search
for a transformative point-of-care test that will identify when
antibiotics are needed and, if they are, which ones to use. This is
vitally important as the incorrect use and overuse of antibiotics is a
major contributor to the rise of antibiotic resistance. We hope that
the Longitude Prize challenge will be a catalyst for further—and
urgent—innovation in developing solutions that address this major
worldwide problem.” –Tim Griffiths, CEO of CPA Global
a method for pinpointing a ship’s location
at sea by knowing its longitude, one of the
greatest scientific challenges of that century.
Antibiotic resistance was chosen by the British public as the focus for Longitude Prize
2014 because, according to the Wellcome
Trust, no new class of antibiotics has reached
the market in 25 years.
“Antibiotic resistance is one of the biggest
global health challenges of our time, which,
if not addressed, could cost millions of lives
around the world,” explained Geoff Mulgan,
chief executive of Nesta and Longitude Prize
committee member. “Our hope is that the
combination of the prize and greater awareness of the problem will fuel a dramatic
acceleration in the search for solutions, many
of which may be surprising and come from
unexpected sources. We are grateful for the
support from CPA Global. The patent landscape study will be a very valuable benchmarking tool for the judging panel when
considering submissions.”
An August feature on Nesta’s website
shared the results of a survey of more than
1,000 general physicians for Longitude Prize,
revealing the need for easy, accessible diagnostic tools. Seventy percent of the survey
participants said they prescribe antibiotics
when they aren’t sure if a patient is suffering from a viral or bacterial infection, and 24
percent said they prescribe them due to a lack
of easy-to-use diagnostic tools. Additionally,
28 percent of the general physicians revealed
that they prescribe antibiotics “several times a
week” even when they aren’t positive they’re
medically necessary, with 90 percent reporting that they feel pressure from patients to
prescribe the antibiotics. More than 50 million antibacterial items were dispensed to the
community in the United Kingdom last year. n
EDITCONNECT: E011520
DIAGNOSTICS
myChoice CDx becomes TESARO’s choice
TESARO directors select
Myriad Genetics’ companion
diagnostic for treating
resistant ovarian cancer
BY LORI LESKO
BARCELONA, Spain—With the ancient Goth-
ic Quarter looming near the site of the hightech 26th EORTC-NCI-AACR Symposium on
Molecular Targets and Cancer Therapeutics,
Myriad Genetics announced biopharmaceutical company TESARO will use Myriad’s
myChoice HRD companion diagnostic (CDx)
to identify tumor tissue with a deficiency in
homologous recombination—good news for
the future of patients suffering from a resistant form of ovarian cancer.
Under the terms of the agreement,
Waltham, Mass.-based TESARO will utilize
Myriad’s test to enrich the target population
for potential responders to niraparib, while
Myriad provides the testing services and pursues the necessary regulatory approvals in support of TESARO’s development of niraparib Myriad Genetics recently announced that biopharma TESARO will use Myriad’s myChoice HRD
as a therapy used for treating ovarian cancer. companion diagnostic to identify tumor tissue with a deficiency in homologous recombination.
In addition, Dr. Paul Haluska, Jr., associate platinum-based therapies or PARP (poly-ADP companion diagnostic to pair a tumor type
with the targeted activity of a specific mediprofessor of oncology at the Mayo Clinic, pre- ribose polymerase) inhibitors.”
“Companion diagnostic collaborations with cine,” Lanchbury said. “Prior studies have
sented new data before the Barcelona sympoinnovative partners are integral to shown that only a subset of patients will
sium, demonstrating that Myriad’s
our long-term research strategy, respond to PARP inhibitors. HRD is the most
myChoice HRD (homologous
and we place a high value on all of comprehensive test to identify those patients
recombination deficiency) score
pharmaceutical company collabo- who might respond to treatment.”
is predictive of niraparib sensitivMyriad estimates the global market for an
rations,” Rogers explains. “Addiity in patient-derived xenograft
tionally, we’re committed to being HRD test could exceed $3 billion as oncolomodels of ovarian cancer.
a leader in personalized medicine gists move toward personalized medicine and
The companies have not disclosed
for cancer patients. In the case of targeted therapies.
the financial terms of the deal.
“As an innovation-focused company, we are
TESARO, our goal is to combine
Mary Lynne Hedley, president
and chief operating officer of “Data have shown our strengths to better understand leading the way in developing breakthrough
the underlying biology of cancer— companion diagnostics that have the potenTESARO, stated in a news release, that patients who
and to drive the development of tial to create significant value for patients and
“Myriad’s myChoice HRD diag- respond to PARP
physicians,” Lanchbury said. “We also strive
anti-cancer therapies.”
nostic test identifies the inherent inhibitors often
“We currently are partnering to be the research partner of choice.”
biology of the tumor and differ- have tumors with
Companion diagnostics continue to be
entiates tumors with homologous certain DNA repair with more than 20 pharmaceutideficiencies—such
cal companies,” he adds. “Our col- developed to identify patients most likely to
repair deficiencies from those as BRCA
laborations include DNA sequenc- benefit from specific treatments and “hold
without such deficiencies. Nirapa- mutations—and
rib sensitivity in patient-derived who may be more ing, RNA analysis, proteomics and tremendous promise in the treatment of disin some instances we combine all eases such as rheumatoid arthritis and other
xenograft models is associated likely to respond
autoimmune disorders, cancer and diabetes,”
three of these technologies.”
with HRD status as defined by the to treatment with
niraparib,” says
Myriad is “committed to being according to Myriad.
myChoice HRD test.”
CEO
In the recent study showing the CDx’s utila leader in companion diagnostics
“TESARO is developing nirapa- TESARO
Lonnie Moulder.
that help target or tailor a treat- ity, patient-derived xenografts were created
rib for several tumor types, and we
have two Phase 3 trials ongoing in patients ment plan for patients,” Rogers says. “Studies from more than 100 high-grade serious ovarwith ovarian cancer and breast cancer,” TESA- are underway, and last month we announced ian cancer tumor samples, Myriad reported.
HRD testing was performed on each samRO CEO Lonnie Moulder tells DDNews. “Data an expansion of our research collaboration
ple using myChoice HRD to define HRD
have shown that patients who respond to with TESARO.”
Jerry Lanchbury, chief scientific officer at status, detect BRCA 1 and 2 mutations and
PARP inhibitors often have tumors with certain DNA repair deficiencies—such as BRCA Myriad, stated in a news release about that identify hypermethylation of BRCA genes.
mutations—and who may be more likely to deal that “We are excited to be expanding our Approximately half of these models were
collaboration with TESARO as we strongly HRD-positive and are being evaluated for
respond to treatment with niraparib.”
While TESARO “is responsible for all believe new diagnostics such as myChoice sensitivity to niraparib in vivo.
Preliminary data from treated models indiaspects of niraparib development, Myriad HRD, combined with targeted therapies
will be responsible for development of the such as niraparib, have the potential to sig- cate all models that responded to niraparib
treatment had an HRD score above the prediagnostic test,” he adds. “We believe that nificantly improve patient care.”
Myriad’s myChoice HRD CDx “utilizes determined cutoff value, and included both
niraparib has the potential to be a meaningful
advancement in the treatment of patients with three proprietary measures to assess the BRCA mutant and BRCA wild-type tumors.
ovarian cancer, breast cancer and potentially genomic scar associated with the loss of Evaluation of niraparib sensitivity across the
other tumors, such as small cell lung cancer.” DNA repair, and has been shown in multiple full set of selected models is ongoing.
Niraparib is an orally active and potent
Ron Rogers, executive vice president of clinical studies to be the most comprehensive
corporate communications at Myriad, spoke predictor of tumor response to DNA damag- PARP, inhibitor. A Phase 1/2 monotherapy
to DDNews about DNA-damaging agents and ing agents such as niraparib,” Lanchbury said. study of niraparib has been completed in
Myriad first announced a collaboration more than 100 patients with advanced
the importance of strategic collaborations
with TESARO last year, on March 24, stating solid tumors. Two Phase 3 trials are curthat set the stage for new discoveries.
“DNA-damaging agents target and inter- that TESARO would use Myriad’s novel HRD rently ongoing to evaluate a single oral
rupt the DNA pathway in tumor cells, which test to identify tumor types that may respond dose of niraparib as a maintenance therapy
result in the tumor cells dying,” Rogers said. to its investigational PARP inhibitor, nirapa- for patients with ovarian cancer and as a
treatment for patients with BRCA-positive
“Patients who have tumors that lack the abil- rib, then in Phase 3 clinical development.
“The biology of cancer is complex, and breast cancer. n
ity to repair the DNA may be more likely to
respond to DNA-damaging agents like the increasingly the goal of oncology is to use a EDITCONNECT: E011523
For more information, visit www.DDN-News.com
NIPT
CONTINUED FROM PAGE 30
standard blood draw. This can avoid
invasive testing, which often carries
with it cost and complications.”
Zabrowski shares Song’s outlook
on this technology, noting that “We
believe cell-free DNA technology is
going to be a game-changer, not only
in NIPT but in other disease areas such
as cancer, transplant and infectious
disease … We think that for us, cellfree DNA technology is an important
strategic imperative for Roche to lead
in this area.”
CREDIT: ROCHE
32 DDNEWS | | JANUARY 2015
“We believe cell-free DNA technology
is going to be a game-changer, not only
in NIPT but in other disease areas such
as cancer, transplant and infectious
disease … We think that for us, cell-free
DNA technology is an important
strategic imperative for Roche to lead
in this area,” says Dan Zabrowski, head
of Roche Tissue Diagnostics and Roche
Sequencing Unit.
He says that going off of analyst estimates, it’s fair to say the NIPT market
“has the potential to be a multibilliondollar market,” adding that though the
market is currently focused on highrisk pregnancies, “we believe that with
Ariosa we can expand access to an
NIPT test that would make it affordable for women who have moderateto low-risk pregnancies.”
Following the close of the transaction, Zabrowski says Roche will retain
Ariosa’s employees and current site in
San Jose, Calif.
“We think Ken Song and his management team are excellent. We’re
really excited that we’re going to be
able to retain everybody at Ariosa,
and they’ll continue to be an important
part of our strategy going forward,” he
tells DDNews. “We remain committed
to developing an integrated portfolio
that provides our customers with a
complete solution for the generation,
analysis and management of genomics data, and for us to achieve that,
we’re investing internally in potential
breakthrough technologies as well as
seeking the most innovative technologies externally, as evidenced by the
announcements we’ve made this year
with the acquisition of Genia, our collaboration with Stratos, the acquisition
of Ariosa and the acquisition of Bina.” n
EDITCONNECT: E011521
For more information, visit www.DDN-News.com
JANUARY 2015 | | DDNEWS 33
BUSINESS &
GOVERNMENT POLICY
BRIEFS
Orphan drug designation for
pancreatic cancer candidate
CAMBRIDGE, Mass.—The FDA has granted MM-141
orphan drug designation for the treatment of
pancreatic cancer, Merrimack Pharmaceuticals
Inc. reported recently. This designation grants
Merrimack seven-year marketing exclusivity for
MM-141 should the drug receive FDA approval.
A Phase 2 study investigating MM-141 combined
with nab-paclitaxel and gemcitabine in frontline
pancreatic cancer is expected to start next year.
Dr. Ulrik Nielsen, Merrimack’s chief scientific
officer and co-founder, said, “We look forward to
advancing the clinical development of MM-141 as
we believe that it has the potential to significantly
inhibit tumor survival signaling and address pathways
of therapeutic resistance in this indication.”
Galena expands patent
portfolio for GALE-401
PORTLAND, Ore.— Galena Biopharma Inc.
announced receipt of a Notice of Allowance from
the U.S. Patent and Trademark Office for a patent
application for GALE-401 composition of matter,
a controlled-release formulation of anagrelide
for use in reducing platelet counts in patients
with myeloproliferative neoplasms. The claims
encompass controlled-release formulations of
GALE-401 in a broad range of unit dosage forms,
articles of manufacture containing GALE-401 and
methods of reducing platelet counts in patients
with a variety of diseases by administering GALE401, and the patent, when issued, expires in 2029.
“This composition of matter patent is an
important component in the building of our patent
family for GALE-401 ... Our controlled-release
version of anagrelide may offer treatment benefits
for patients [who] may not be tolerating the currently
available immediate-release version,” said Dr. Mark
W. Schwartz, Galena’s president and CEO.
MedImmune boosts cancer Patent Docs
capacities with Definiens deal Copyright
by Kevin Noonan
Acquisition brings with it
Tissue Phenomics, an
imaging technology for
biomarker identification
law
threats to
U.S. drug
innovation
BY KELSEY KAUSTINEN
LONDON—In its latest move to strengthen
its oncology position, MedImmune, the global biologics research and development arm
of AstraZeneca, has acquired privately held
Definiens, a data-analysis firm with corporate
headquarters in München, Germany, and
American headquarters in Carlsbad, Calif.
Per the agreement, MedImmune will acquire
100 percent of Definiens’ shares for an initial
consideration of $150 million and will also
make additional, predetermined milestone
payments. The transaction was expected to
close in the fourth quarter of 2014.
Among Definiens’ portfolio is Tissue Phenomics, an imaging and data-analysis technology that can dramatically improve the
identification of biomarkers in tumor tisCANCER CONTINUED ON PAGE 34
to win FDA marketing approval by submitting bioequivalence studies.
The case that had reached the Supreme
DELAY CONTINUED ON PAGE 35
PATENT CONTINUED ON PAGE 36
Looking to strengthen its oncology position,
MedImmune (the headquarters of which is
pictured here) will acquire 100 percent of
Definiens’ shares for an initial consideration
of $150 million and will also make additional,
predetermined milestone payments.
PAY TO DELAY?
Ranbaxy and AstraZeneca
win jury victory in test
of what antitrust limits
may be placed on reverse
payment deals
BY ILENE SCHNEIDER
IN THIS SECTION
Copyright law/Innovation
Patent Docs: Copyright law threats
to U.S. drug innovation��������������������������� 33
Litigation/Antitrust
Pay to delay?........................................... 33
M&A activity
MedImmune boosts cancer capacities
with Definiens deal................................. 33
Merck to pay $8.4 billion for Cubist
(CUBIST from cover)................................ 36
Oncology/Orphan drugs
Orphan drug designation for
pancreatic cancer candidate................... 33
Patent activity
Galena expands patent portfolio
for GALE-401........................................... 33
Tools and technology
On the cutting edge................................. 34
BOSTON—A Massachusetts jury has found
that an agreement between AstraZeneca, the
global biopharmaceutical giant, and Ranbaxy
Laboratories Ltd., a generics drugmaker, to
delay the introduction of a generic version of
AstraZeneca’s heartburn drug Nexium was
not anticompetitive.
The verdict, reached Dec. 5 in federal court
in Boston, is the first time a jury has decided
such a case since the U.S. Supreme Court
ruled in June 2013 that “so-called pay-fordelay settlements may run afoul of antitrust
laws,” according to the New York Times—in
other words, whether the Hatch-Waxman
Act settlements could be challenged under
federal antitrust law. The Drug Price Competition and Patent Term Restoration Act of
1984, usually referred to as the Hatch-Waxman Act, was designed to promote generics
while leaving intact a financial incentive for
research and development. It allows generics
O
NE OF THE POWERS OF
Congress conferred
by the Constitution
is to grant copyright
and patent protection;
these powers are enumerated in the
same part of Article I, specifically in
Section 8, Clause 8:
To promote the Progress of Science and
useful Arts, by securing for limited Times
to Authors and Inventors the exclusive
Right to their respective Writings and
Discoveries.
This coincidence
of these powers has
raised questions of
whether development of the law in
one area can affect
the law in the other;
Kevin Noonan,
for example, with partner,
regard to concepts McDonnell
such as exhaustion Boehnen
and extraterritori- Hulbert &
ality. Both of these Berghoff LLP
issues arose in the copyright case of
Kirtsaeng v John Wiley & Sons decided
by the U.S. Supreme Court last term;
while the immediate effect of this decision on patent law was unclear, recent
developments may make the case very
relevant and very dangerous for continued pharmaceutical innovation.
Briefly, the case involved a copyright infringement action brought
by Wiley against a Thailand national,
Supap Kirtsaeng, who was studying in
the United States and arranged to have
copies of textbooks sold in Thailand
sent to him by his relatives for resale in
the United States. Because Wiley (like
many U.S. publishers) sells the same
textbook at a much lower price in
countries like Thailand than they cost
in the States, Kirtsaeng was able to sell
the books sent to him from abroad on
eBay, ultimately making $1.2 million
A jury decision recently found that an
agreement between AstraZeneca (R&D
activities of which are pictured here) and
generic drugmaker Ranbaxy to delay the
introduction of a generic version of
AstraZeneca’s heartburn drug Nexium was
not anticompetitive.
BUSINESS & GOVERNMENT POLICY
34 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
A roundup of instrumentation, software
and other tools and technology news
A
BY JEFFREY BOULEY
S WE LOOK AT SOME
of the interesting
technologies available to improve the
work of life-sciences
researchers and lab
staff, we will see some
“walkers” (no, not the
kind from “The Walking Dead,” thankfully),
computational chemistry software, biologics
de-risking and sequencing analysis.
TOOLS &
TECHNOLOGY
Microscopic “walkers” find their
way across cell surfaces
CAMBRIDGE, Mass.—In a case of
technology that could provide a
way to deliver probes or drugs to
cell structures without outside
guidance, a team of researchers
at the Massachusetts Institute of
Technology (MIT) led by Alfredo
Alexander-Katz, the Walter Henry
Gale Associate Professor of Materials Science and Engineering, has
CANCER
CONTINUED FROM PAGE 33
sue. Tissue Phenomics is based on
Definiens’ proprietary Cognition
Network Technology, which was
developed by Prof. Gerd Binnig, the
1986 Nobel Laureate in Physics, and
helps mine information from cancer tissue samples by measuring the
identity, locations and relationships
between the different components
of the tumor microenvironment.
The company received Frost & Sullivan’s 2013 Global Company of the
Year for Tissue Diagnostics and
Pathology Imaging Solutions award.
“Definiens’ Tissue Phenomics
approach marks a significant step
toward closing the gap between
MedImmune, the
global biologics
research and
development arm of
AstraZeneca (the
headquarters of which
is pictured here), has
acquired privately held
Definiens, a dataanalysis firm with
corporate headquarters
in München, Germany,
and American
headquarters in
Carlsbad, Calif.
demonstrated a new target-finding
mechanism. The new system allows
microscopic devices to autonomously find their way to areas of
a cell surface, for example, just by
detecting an increase in surface
friction in places where
more cell receptors are
concentrated.
“The idea was to find
out if we could create
a synthetic, active system that could sense
gradients in biological receptors,”
Alexander-Katz explains. “Currently, we don’t know of anything
that can do that.”
Cells have a way of locating areas
that bear a specific kind of chemical signature—a process called chemotaxis. That’s the method used by
white blood cells, for example, to
locate regions where pathogens are
attacking body cells.
The new system uses a pair of
linked particles with magnetic
properties. In the presence of a
genomics and patient outcomes,”
Thomas Heydler, CEO of Definiens, commented in a statement.
“We look forward to joining the
MedImmune team as Tissue Phenomics is of particular importance for personalized medicine
in immuno-oncology. Definiens’
unique ability to extract information from tissue images enables us
to find novel markers for patient
stratification by correlating tissue information with clinical outcomes. Together, MedImmune and
Definiens can bring tailored treatments to patients faster.”
There are a number of reasons for
this deal, says Ed Bradley, a senior
vice president at MedImmune
and head of iMED (Innovative
magnetic field, the paired particles
begin to tumble across a surface,
with first one particle and then the
other making contact—in effect,
“walking” across the surface.
So far, the work has been carried out on a model cell surface,
on a functionalized microscope
slide, but the effect should work
similarly with living cells, Alexander-Katz says. The team’s goal
now is to demonstrate the ability
of the microscopic walkers to find
their way toward concentrations
of receptors in actual living tissue.
The method could potentially
have a variety of applications,
Alexander-Katz says. For example,
it could be developed as a method
of locating tumor cells within the
body by identifying their surface
texture, perhaps in combination
with other characteristics.
Nagoya University institute
licenses Cresset’s computational
chemistry software
CAMBRIDGE, U.K.—Cresset, innovative provider of computational
chemistry software and services,
CREDIT: JOHN PHELAN
ON THE CUTTING EDGE
MIT researchers have developed a new system that allows microscopic
devices to autonomously find their way to areas of a cell surface.
announced in late fall 2014 that
Nagoya University’s Institute of
Transformative Bio-Molecules
(ITbM), located in Nagoya, Japan,
has licensed Cresset’s Forge, a computational chemistry suite for understanding SAR and molecular design.
“The focal point of ITbM is to
develop transformative bio-molecules that will be key to solving
urgent problems at the interface
of chemistry and biology,” says
Associate Prof. Ayato Sato, head of
the Research Promotion Division
and the chief coordinator of the
ITbM Chemical Library Center.
“We are confident that licensing
Cresset’s software will accelerate
our research to find candidates of
transformative bio-molecules.”
Chugai licenses EpiVax platform
to de-risk biologics
PROVIDENCE, R.I.—Chugai Pharmaceutical Co. Ltd. recently signed
an agreement with Rhode Islandbased biotechnology company EpiVax Inc. to incorporate EpiVax’s
ISPRI (Interactive Protein Screening and Reengineering Interface)
immunogenicity screening and
EDGE CONTINUED ON PAGE 36
One of the assets that will be gained by MedImmune (a facility of which is pictured here) by acquiring Definiens is
Tissue Phenomics, an imaging and data-analysis technology that can dramatically improve the identification of
biomarkers in tumor tissue.
Medicines and Early Development).
For one, MedImmune has worked
with Definiens for years, in multiple
therapeutic areas and across both
biologics and small molecules, he
explains. Definiens’ technology was
also an important factor. A major
feature, however, was the volume of
work MedImmune’s portfolio was
generating, Bradley explains.
“Their technology enables the
very precise characterization of
change of immunologic biomarkers
in patients’ tumors as therapy is
progressing, and the ability to
get that data really will help us
guide a lot of decisions we make
about identifying exactly the right
combinations of agents to use,”
Bradley tells DDNews. “Our portfolio
is really based on identifying the
best, most active combinations of
immunotherapies to use in patient
care, and so we were finding that we
were doing more and more of this
translational work with Definiens
and in just looking forward over the
next couple of years realized that
we could completely occupy all of
the capacities that they have, and so
the acquisition really made a lot of
sense.”
Oncology is a core therapeutic
area for AstraZeneca and MedImmune, making the technological support Definiens can offer
of significant value for pipeline
development. Bradley says he considers cancer immunotherapy to
have the potential to become “the
core of effective cancer therapeutic
regimens moving forward, primarily because an effective immune
response lasts a lifetime and it has
the greatest possibility in resulting
in very, very durable response.” He
considers it particularly central to
AstraZeneca given the company’s
small molecules and MedImmune’s
immunotherapeutics, which
together, Bradley says, offer “an
enormous amount of synergistic
potential, therapeutic potential.”
In a press release detailing the
completion of the acquisition,
Definiens noted that the deal “will
help to accelerate further clinical
programs through precise predictive
and prognostic biomarker testing.
It is believed that using biomarkers
to select patients for clinical trials
could potentially shorten clinical
timelines and increase response
rates. As a result, the technology
will serve as an important tool in
the advancement of the most promising combination therapies across
AstraZeneca’s combined small-molecule and biologics pipeline, around
80 percent of which currently has a
personalized healthcare approach.”
“It’s extremely important to
understand the biology of the
immune response to cancer and
to understand the pharmacologic/
pharmacodynamic effect that you’re
having by using these immune
checkpoint modulators in patients,”
Bradley tells DDNews. “And the
Definiens technology enables you,
in a small number of patients in a
very accurate way, to see exactly
what biological, pharmacodynamic
effect you’re having, so this is central to the strategy of having a very
strong translational core for all of
the programs we have.”
Following the completion of this
deal, Bradley says Definiens will
retain its employees and continue
operating its business with third-party customers on a contractual basis. n
EDITCONNECT: E011524
For more information, visit www.DDN-News.com
DELAY
CONTINUED FROM PAGE 33
Court was filed by the U.S. Federal
Trade Commission, which maintains that “reverse payments” cost
drug buyers as much as $3.5 billion
a year—the agency noted that in
2012 alone, 40 such reverse payment deals were struck. The pharma industry not only disputes the
$3.5-billion number and argues
deals like these are legal, but also
largely maintains that such deals
allow lower-cost generic drugs to
reach consumers faster than if patent litigation cases are filed and
drag on.
Plaintiffs, who included drug
wholesalers and insurers, claimed
that generic Nexium could have
been on the market as long as six
years ago. They also argued that
Ranbaxy could have begun selling a
generic version “at risk,” resulting
in a cheaper version being available earlier.
Venable LLP, led by partner J.
Douglas Baldridge, represented
Ranbaxy in the suit in Federal
District Court in Boston. Ranbaxy
and AstraZeneca challenged a 2008
settlement of a patent lawsuit that
stalled sales of a cheaper version of
Nexium in the United States until
AstraZeneca’s patents expired last
May. The legal firm, which includes
600 attorneys in six offices and
specializes in antitrust litigation,
described the suit as “the first test
of what limits may be placed on
reverse payment deals among drugmakers to protect steady streams of
revenue on popular drugs.”
The Venable team for the sixweek trial consisted of partners J.
Douglas Baldridge, Lisa Jose Fales
and Danielle R. Foley, associates
Vincent Verrocchio, Paul Feinstein, Sarah Choi and Molly Cusson
with Marta Markowska and Jeanne
Mooney. Led by Douglas Baldridge,
the Venable trial team emphasized
the fact that even though the date
for generic entry had come and
gone, no generic received even
tentative approval from the FDA
for another similar drug.
Baldridge pointed to the fact
that the jury clearly agreed with
the defendants’ argument dismissing the idea that “but for so-called
‘illegal’ payments by the defendants,
the plaintiffs could have entered the
market at an earlier date. Clearly
that did not occur,” Baldridge said.
“The system worked. The jury
understood the facts of the case and
were not swayed by wishful thinking on the part of the plaintiffs,” he
said in his closing arguments. “The
drug buyer groups were living in
a fantasy world during the trial.
No company could have produced
generic Nexium sooner because
none of the generics makers had
FDA approval.”
Ranbaxy had said in an earlier court filing that, “The buyers
failed to show they were actually
harmed by the deal between the
companies,” relying instead upon
BUSINESS & GOVERNMENT POLICY
“strained opinions of experts who
each proffer a version of what could
have or would have happened in a
hypothetical world that has no connection to the evidence.”
Fales, another of the Venable
team, believes that the case was
successful for Ranbaxy, because
“The legal system worked, and the
jury got it. The jurors understood
that there was a lack of causation
in the plaintiff’s case. We also had a
cohesive legal team that helped the
jurors to separate the wheat from
the chaff.”
Fales explained that given the
length and complexity of the case,
the fact that it was essentially
deliberated in a day by the jurors
proves that reality trumped the
hypothetical case posited by the
plaintiffs. “The jurors understood
the complicated legal and technical
issues of how the Hatch-Waxman
legislation works, how business
works and how drug companies
operate,” she concluded. n
EDITCONNECT: E011525
JANUARY 2015 | | DDNEWS 35
In a suit recently decided in federal court in Boston, Ranbaxy and
AstraZeneca (the headquarters of which is pictured here) challenged a 2008
settlement of a patent lawsuit that stalled sales of a cheaper version of
Nexium in the United States until AstraZeneca’s patents expired last May.
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PATENT
CONTINUED FROM PAGE 33
in revenues. Although Wiley prevailed in the lower courts, the
Supreme Court reversed, on the
grounds that the “first sale doctrine” permitted resale of legally
obtained copyrighted works
without obtaining the copyright
owner’s permission, and that U.S.
copyright law, and the notice on
the textbooks purchased in Thailand that they were only authorized for sale outside the U.S.,
did not mandate a different outcome. (Not unexpectedly, Wiley
increased the cost of its textbooks
sold abroad after this decision.)
This case has clear implications for branded drugs, which
are often sold outside the U.S. for
less than the same drugs costs at
home; at least some of these cost
differences are the result of foreign governments imposing price
caps and otherwise regulating the
cost of branded drugs. This is not
a phenomenon limited to developing or Third World countries:
many European countries having
a nationalized healthcare system
also have varying levels of cost
controls for branded drugs, along
with regimes for generic versions
of these drugs after expiration
of some term of exclusivity for
the branded versions. And many
countries, such as Brazil, China,
India, Russia and Thailand, have
relied upon international treaty
provisions (such as the Doha
Declaration under the auspices of
the World Trade Organization) to
provide government-subsidized
generic versions of branded drugs
at prices much lower than the prevailing price in Western countries.
These differences in costs have not
affected U.S. prices because, unlike
textbooks, branded drugs cannot
CUBIST
CONTINUED FROM PAGE 1
it can have the greatest impact
in addressing significant unmet
medical needs while delivering
the greatest value to customers
and society.
“Cubist is a global leader in antibiotics and has built a strong portfolio of both marketed and late-stage
pipeline medicines,” according to
Kenneth C. Frazier, chairman and
CEO of Merck. “Combining this
expertise with Merck’s strong capabilities and global reach will enable
us to create a stronger position in
hospital acute care while addressing critical areas of unmet medical
need, such as antibiotic resistance.”
Merck has strategically focused
on acute care within the larger
hospital setting as a top priority
because of the significant unmet
need and the unique opportunities
for Merck to improve patient care
and manage costs in this setting
with its in-line portfolio, promising
BUSINESS & GOVERNMENT POLICY
be reimported into the U.S. under
FDA regulations and U.S. law.
That may be changing, however,
in view of a New York Times report
recently on bipartisan efforts to
reduce drug prices by permitting
reimportation. The Times reports,
in an article by Elisabeth Rosenthal, that Sen. Amy Klobuchar
(D-MN) is planning to revive a
prior bill that would permit reimportation from Canada, a country
whose national health service
regulates the price of branded and
generic drugs. She is supported
in these efforts by Sen. John
McCain (R-AZ), and undoubtedly other senators will join in
the effort. The impetus for action
now, according to Rosenthal, is
not that branded drug prices are
high (although there is certainly
concern about the price of some
drugs, particularly biologic drugs
directed towards intractable diseases like cancer); rather, it is the
rising price of generic drugs that
has raised concerns.
A panel of the Senate Subcommittee on Primary Health and
Aging chaired by Sen. Bernie
Sanders (I-VT) investigated the
issue, hearing from Prof. Stephen
Schondelmeyer of the University
of Minnesota, Dr. Aaron Kesselheim of the Harvard Medical
School and Rob Frankil, who testified on behalf of the National
Community Pharmacists Association who had requested congressional action. (Three generic drug
company executives declined the
panel’s invitation to testify, according to the Times report.) The testimony included reports of generic
drug costs increasing by about
8,000 percent (i.e., 80-fold, for
doxycycline) and over 300 percent
for 10 other generic drugs.
These increases are recent (over
the past few months), and the
pipeline and its customer capabilities, the company reports.
Cubist’s antibiotic Cubicin, the
only approved once-a-day therapy
for both S. aureus bacteremia and
complicated skin and skin structure
infections, has been used to treat
more than two million patients
and continues to be an important
therapy in the acute-care environment. Cubist’s in-line and late-stage
pipeline of anti-infective medicines, including Zerbaxa, which
is pending approval from the U.S.
Food and Drug Administration, is
expected to enhance Merck’s hospital acute-care business in a variety of therapeutic areas, including
Gram-positive and Gram-negative
multidrug-resistant infections.
“Combining with Merck is an
exciting opportunity to accelerate
Cubist’s established leadership in
antibiotics and deliver significant,
certain and immediate value to
shareholders,” said Michael Bonney, CEO of Cubist, when the deal
was announced. “We have a deep
causes attributed to the increases
range from shortages in active
pharmaceutical ingredient supplies, manufacturing problems
and consolidation of drug companies by mergers and acquisitions.
As can be expected, the Senate
panel heard calls for greater government regulation and application of drug rebate requirements
to Medicare and Medicaid to apply
to generic drugs, just as they now
apply to branded drugs.
More troubling in the long term
is the solution proposed by Senator
Klobuchar, allowing importation
from Canada; Maine is already
permitting its residents to purchase some drugs from Canada,
Great Britain, Australia and New
Zealand, in contravention of U.S.
law. The crisis in the cost of generic
drugs has made this solution particularly attractive, because paradoxically, the cost of a generic version of a drug in the United States
can be higher than the cost of the
branded drug in Canada. The Times
article illustrated this situation for
digoxin, where a 90-day supply of
the generic drug costs $187 in New
York while the same amount of the
branded version, sold as Lanoxin,
costs $24.30 in Canada. The comparisons are similar for an inflammatory bowel disease drug ($1,625
for the generic in the U.S., $155.70
for the branded version in Canada)
and the cholesterol drug Pravachol
($230 U.S. generic/$31.50 branded
Canadian). With these differential
costs, plans permitting branded
drug reimportation have begun to
have political force, reinforced by
the aging of the population where
more people will be covered by
Medicare and costs to the government will rise accordingly.
If successful, these efforts will
create a situation akin to the consequences of the Kirtsaeng case
For more information, visit www.DDN-News.com
in the copyright arena. Here,
however, innovator drug companies will not have the option,
exercised by Wiley, of increasing
prices abroad to make reimportation less economically attractive.
The prevalence of ANDA litigation in the U.S. over the past 30
years is one indication of the
importance of exclusivity, and
the attendant profits that result
from exclusivity, to pharmaceutical innovation. Should those
profits decrease significantly, the
return on investment (ROI) for
innovator drugs will fall, and the
calculus of investment that supports new drug development will
be affected unpredictably (but not
positively; the unpredictability
resides in how much the ROI will
change and how that will affect
investment decisions).
A common criticism aimed at
branded drugmakers is the frequency with which they develop
“me too” and next-generation
versions of already-marketed
drugs rather than create innovative new treatments and therapies. The same uncertainties in
drug development that make
such behavior sound economically also impact the decision to
develop new drugs, and policies
that reduce ROI for such new
drugs (which bear the greatest
economic risk) are unlikely to
promote innovation. n
EDITCONNECT: E011526
Kevin Noonan is a partner with
the law firm McDonnell Boehnen
Hulbert & Berghoff LLP and
represents biotechnology and
pharmaceutical companies on
a myriad of issues. A former
molecular biologist, he is also
the founding author of the Patent
Docs weblog, http://patentdocs.
typepad.com/.
“Cubist is a global leader in antibiotics and has built
a strong portfolio of both marketed and late-stage
pipeline medicines,” says Kenneth C. Frazier,
chairman and CEO of Merck. “Combining this
expertise with Merck’s strong capabilities and global
reach will enable us to create a stronger position in
hospital acute care while addressing critical areas of
unmet medical need, such as antibiotic resistance.”
respect for Merck, and it is clear
that they share our commitment
to addressing the growing, global
problem we are facing in combating antibiotic-resistant bacteria.”
Merck isn’t alone among large
pharmas in looking at antibiotics
with a new eye in the face of rising
antibiotic-resistant disease rates,
but some think the company may
be overreaching with this acquisition deal. As noted in coverage
by the New York Times, immediate investor response was to wipe
away some $8 billion—almost the
entire purchase price—from Merck’s market capitalization, in part
because a legal decision in Cubist vs.
Hospira in the U.S. District Court
in Delaware could force Cubist to
face generic competition for Cubicin in the United States as early
as the middle of 2016 rather than
2020. Although the Times noted
this was probably an overreaction
on the part of investors, because
even a worst-case scenario probably
means foregone Cubicin revenue
would not likely exceed $3 billion,
it shows that many don’t have the
same level of faith in the deal as
Merck does.
As Leerink Research notes, the
district court ruling was in favor
of Hospira on all but one of five
patents that Hospira had said were
infringed by Cubist.
“Barring a rapid appeal over-
EDGE
CONTINUED FROM PAGE 34
deimmunization technology into
Chugai’s drug development toolbox. Researchers at Chugai will utilize the cloud-based in-silico ISPRI
in conjunction with OptiMatrix, a
tool for deimmunizing biologics, to
screen and re-engineer therapeutic
proteins for potential immunogenicity and deimmunize immune-dominant epitopes, known as clusters.
Dr. Tomoyuki Igawa, group manager of the Discovery Research
Department at Chugai, said that
“Integration of ISPRI into the
Chugai’s antibody engineering and
optimization platform will reduce
the immunogenicity risk and
increase the likelihood of successful clinical development for important, human life-saving biologics.”
Software selected to automate
and standardize NGS data analysis
TOKYO—Genedata, a provider of
software solutions for drug discovery
and life-sciences research, recently
announced that Takara Bio Inc., a
global biotech, has chosen Genedata
Expressionist for Genomic Profiling
as its key software platform for nextgeneration sequencing (NGS) data.
The platform will be integrated with
in-house and third-party data analysis tools and databases, providing a
single integrated environment for
fully automated multi-omics data
processing and comprehensive data
management.
“We are committed to deliver
innovative services and highestquality data to our customers. Genedata helps us to continue to deliver
on our promise by providing a software platform which automates and
manages NGS data analysis workflows for all relevant applications,”
noted Masanari Kitagawa, executive
officer of Takara Bio. n
EDITCONNECT: E011527
turning the judge’s ruling on at
least one of the four patents, we
would expect several generics to be
introduced in late-2016, assuming
Cubicin receives pediatric exclusivity,” wrote Seamus Fernandez
and Aneesh Kapur of Leerink. “In
a press release commenting on
the decision, [Cubist] specifically
noted that ‘the transaction with
Merck is unaffected.’”
Leerink noted that Cubist
expects a rapid appeal, and the
firm’s note about the deal indicates that “This decision clearly
increases the importance of selling the strategic importance” of
the deal with Cubist. The Leerink
analysts also expect increased scrutiny of Cubist’s Zerbaxa launch in
the United States and Europe.
Overall, they note, Merck’s price
for Cubist looks to be between $2
billion and $3 billion too high,
adding: “This is a very tough start
to a relatively sound strategic deal
in our view.” n
EDITCONNECT: E011502
For more information, visit www.DDN-News.com
AWARDS & HONORS
JANUARY 2015 | | DDNEWS 37
Awards & Honors
EINDHOVEN, The Netherlands—
The IntelliCap electronic oral
drug delivery technology, created
by Medimetrics, recently won the
European High-Tech Innovation
Award from Accenture, a global
management consultancy.
The IntelliCap system was
introduced into the market in 2011,
and as Medimetrics explains, an
increasing number of pharmaceutical
companies are using this tool in
the early-stage development and
lifecycle management of drugs.
As the company puts it, “This
unique, interactive device enables
personalization of medications and
treatments, empowering scientists
to establish quickly the effective
medication dose and delivery
requirements. This reduces the
risk of failure in expensive, latestage clinical trials due to lack of
safety or efficacy.”
An early example of IntelliCap’s
use is in the field of women’s health,
where Dutch company LiGalli is
integrating the technology into a
novel vaginal drug delivery system
that enables new therapies. In
another example, IntelliCap
technology has allowed for a means
of sampling and mapping content
from the small intestine to identify
its microbiological composition in
a noninvasive way which, among
other things, can provide novel
insights into how therapeutic
agents might react in the gut and
affect patients’ health.
“The spirit of the award was
to recognize the potential of the
IntelliCap technology. Its ability
to adapt and personalize during
delivery will help usher in an era of
smart pharmaceuticals to the benefit
of patients,” said Olaf Weiner, CEO
of Medimetrics. n
CREDIT: MEDIMETRICS
IntelliCap oral drug delivery system
wins European innovation award
Illustrated here is a cross-section of the IntelliCap electronic oral drug
delivery technology.
Magid Abou-Gharbia wins
Dr. Trey Westbrook
Grand Hamdan award
recognized by TAMEST
for innovation in medicine
PHILADELPHIA—Mid-December saw the
chair of molecular and human
HOUSTON—Baylor College of
genetics at Baylor. “Leveraging
Medicine researcher Dr. Thomthese innovations, he identias “Trey” Westbrook has been
fied unique molecular vulnernamed The Academy of Mediabilities in human cancer that
cine, Engineering & Science of
have culminated in new theraTexas’ (TAMEST) 2015 Edith
pies for breast cancer patients.”
and Peter O’Donnell Award
Some of Westbrook’s most
winner in medicine, an honor
recent work identified new
given annually to one scientist
genes that drive triple negative
in the state for outstanding Dr. Thomas
Westbrook, Baylor
breast cancer, an aggressive and
innovation in medicine.
difficult to treat form of the disWestbrook, an associate pro- College of
Medicine
ease with little understanding
fessor of molecular and human
genetics and of biochemistry and molecu- of the molecular and genetic mechanisms
lar biology at Baylor, has made significant that lead to its development. This work has
contributions to medicine by using novel led directly to new therapies for patients
technology developed in his lab to discov- with triple negative breast cancer that are
being tested at Baylor and elsewhere.
er new genes that contribute to cancer.
Initiated in 2006, the O’Donnell Awards
“Dr. Westbrook is a recognized leader
in cancer genetics. He developed trans- are named in honor of Edith and Peter
formative RNA interference screening O’Donnell, who are among the state’s
technologies that have broadly impacted staunchest advocates for excellence in scibiomedical research nationally and inter- entific advancement and science, technolnationally,” said Dr. Brendan Lee, interim ogy, engineering and medical education. n
announcement that Temple University’s Dr.
Magid Abou-Gharbia has won the Grand Hamdan International Award in Drug Discovery.
Abou-Gharbia—who is Temple’s Laura H.
Carnell Professor of Medicinal Chemistry,
associate dean for research and director of the
Moulder Center for Drug Discovery Research
in the university’s School of Pharmacy—won
the award in recognition for his outstanding
contributions and pioneering work in medicinal chemistry and the discovery of several
drugs, including the anticancer drug Torisel, as
well as the antidepressants Effexor and Pristiq.
His Highness Sheikh Hamdan Bin Rashid
Al Maktoum, Deputy Ruler of Dubai and
Minister of Finance, presented the award
at the Dubai International Conference for
Medical Sciences. Abou-Gharbia delivered
the keynote lecture there on the discovery
of innovative small molecules therapeutics
on Dec. 15.
“Dr. Gharbia is a highly esteemed and
internationally renowned scientist whose
many outstanding contributions in research
and innovations in drug discovery are changing the world,” said Temple University Provost Hai-Lung Dai. “This award is a great
honor and a significant milestone, befitting
the stature of Magid Abou-Gharbia.”
During his nearly 30 years at Wyeth Laboratories, Abou-Gharbia had a career underscored by numerous scientific achievements.
His novel approach to drug discovery and
new modes of therapy enabled him to identify new drugs, and his marketed drug discoveries include Mylotarg, Torisel and Bosulif
for the treatment of cancer, and drugs for
other important diseases such as osteoporosis (Conbriza), depression (Effexor, Pristique), insomnia (Sonata) and bacterial
infections (Tygacil).
As the director of the Moulder Center
for Drug Discovery Research at the Temple
University School of Pharmacy since 2008,
Abou-Gharbia has continued his pursuit
of new discoveries with a strong focus on
medicinal chemistry. Abou-Gharbia manages
several labs and collaborative relationships
with other universities and corporations.
Since joining Temple, the Moudler Center
has seen a tremendous growth in research
collaboration and discovery. It currently has
14 patent applications, over a dozen research
papers, millions of dollars in grants and collaborative agreements with organizations
that give the Moulder Center access to stateof-the-art-technology. n
SQZ Biotech awarded grand prize from MassChallenge
BOSTON—SQZ Biotech was recent-
ly awarded a $100,000 grand prize
in MassChallenge’s 2014 startup
competition. The company was
founded to commercialize CellSqueeze, an innovative platform
that reportedly enables virtually any
material to enter a cell with unprecedented efficiency. This capability
has many applications in biomedical research and drug development,
including studying disease mecha-
nisms, identifying novel drugs
and engineering cell function for
therapeutic use. The company was
selected from a pool of 26 top startups, which were chosen from 1,650
applicants globally.
In addition, Boeing and the
Center for the Advancement of Science in Space, or CASIS, awarded
SQZ Biotech the CASIS-Boeing
Prize for Technology in Space, a
more than $200,000 prize, and
will facilitate the use of SQZ Biotech’s CellSqueeze technology on
the International Space Station.
SQZ Biotech’s scientists will study
CellSqueeze in the unique microgravity environment offered by the
station.
Many diseases and disorders
result from dysfunction at the cellular level; however, studying them
has proven challenging as it is currently difficult to understand and
manipulate cells’ internal biological
mechanisms.
SQZ Biotech describes its CellSqueeze platform as “a microfluidic chip that enables the delivery
of virtually any material into almost
any cell type, including primary
human-derived cells, in order to
address challenges with traditional
intracellular delivery technologies.”
SQZ Biotech’s chips contain 75 parallel fluidic channels, each of which
has at least one region where the
channel diameter is smaller than
the diameter of a cell. Cells flowing
through these channels experience
a “squeeze” as they travel through
the narrow point. The mechanical
stress opens temporary holes in the
cell membrane, exposing the cytoplasm, which allows the cell to take
up molecules in the surrounding
environment. Cells repair themselves shortly thereafter. n
PRODUCTS & SERVICES
38 DDNEWS | | JANUARY 2015
For more information, visit www.DDN-News.com
ADVERTISER ’S INDEX
AACR Conference .................................................27 www.aacr.org
Bridging in-vitro and in-vivo
screening: acumen Cellista
TTP Labtech
Bio-Rad Laboratories, Inc. ..................................40 www.bio-rad.com
TTP Labtech’s acumen Cellista has
played a pivotal role in the
miniaturization and optimization of
physiologically relevant cell-based 2D
and 3D assays to make them amenable
for the screening of high-impact
compound libraries. Learn more from an
NCATS case study at our SLAS
workshop “Evaluating Cancer Drug
Candidates Using High-Throughput 3D
Cell Culture Models” on Tuesday, Feb. 10,
at 12:30 p.m. in Room 159AB during the
SLAS 4th Annual Conference &
Exhibition.
https://discover.ttplabtech.com/2015SLAS-landing-pages_acumenworkshop-LP.html
SEE US AT SLAS BOOTH 1329
iAutomate—Lab
automation made easy
Celebrating 25 years
Automated liquid handling
BMG LABTECH
Gilson
In its 25th anniversary year, BMG
LABTECH will showcase its latest
innovations in microplate reading
technology. The CLARIOstar with new
Atmospheric Control Unit offers filterlike performance with advanced LVF
Monochromators that provides
increased sensitivity and flexibility. The
PHERAstar FS is the ultimate microplate
reader for high-throughput screening,
combining the highest sensitivity with
the fastest read times.
www.bmglabtech.com
SEE US AT SLAS BOOTH 929
PIPETMAX can help you maximize
reproducibility of your biological sample
prep. Manual sample preparation can
be inefficient, complex and time
consuming. This leads to increased
training requirements, preparation time,
procedural errors and operational
costs. The Gilson PIPETMAX is an easyto-use, automated liquid-handling
platform that can mitigate these
problems with automated sample
preparation solutions.
www.pipetmax.com
SEE US AT SLAS BOOTH 1307
Thermo Scientific
Take the smart approach to laboratory
automation configuration with Thermo
Scientific iAutomate. Completely free to
use, this intuitive online tool can help
you to easily plan and design a
laboratory automation project that suits
your specific workflow requirements.
Laboratory automation configuration
doesn’t have to be complicated.
www.thermoscientific.com/iautomate
SEE US AT SLAS BOOTH 423
Opera Phenix High
Content Screening System
PerkinElmer
The Opera Phenix High Content
Screening System from PerkinElmer
enables high-throughput phenotypic
screening and analysis of complex
cellular models, such as microtissues
and stem cells, at high speed and
sensitivity. The system’s innovative
Synchrony Optics let you generate
richer information through extremely
sensitive confocal imaging and at
higher throughput than ever through
simultaneous acquisition, without the
issue of crosstalk—for more speed and
more sensitivity, no compromise.
www.perkinelmer.com/OperaPhenix
SEE US AT SLAS BOOTH 523 & 537
INTEGRA focus on liquid
handling at SLAS 2015
BMG LABTECH GmbH............................................5 www.bmglabtech.com
Cambridge Healthtech Institute ........................17 www.healthtech.com
Cisbio US, Inc. .........................................................7 www.htrf.com
Gilson, Inc.................................................................3 www.gilson.com
INDIGO Biosciences ............................................19 www.indigobiosciences.com
Offenberger & White, Inc......................................2 www.offwhite.com
PerkinElmer ...........................................................23 www.perkinelmer.com
TTP Labtech Ltd.....................................................13 www.ttplabtech.com
Thermo Fisher Scientific .....................................21 www.thermoscientific.com
INTEGRA Biosciences
INDIGO expands the largest
industry-leading portfolio of
nuclear receptors
At SLAS 2015, product specialists from
INTEGRA will be on hand to
demonstrate and answer questions on
the company’s popular range of
productivity-enhancing liquid-handling
products. Handheld pipetting requires
practice to achieve steady, reproducible
pipetting results. The VIAFLO ASSIST is
an innovative device that, in
combination with a VIAFLO II electronic
handheld pipette, enables the pipette’s
protocols to be performed automatically.
www.integra-bioscience.com
SEE US AT SLAS BOOTH # 1227
INDIGO is a leader in innovative
products and services that improve the
speed, cost and risks involved in the
drug discovery process. INDIGO’S
newest nuclear receptor products and
services include ERRg, AhR and NFkB,
which complement a comprehensive
panel of products and services
currently offered by INDIGO. For a
complete list, visit our website, and be
sure to KNOW INDIGO.
www.indigobiosciences.com
[email protected]
INDIGO Biosciences Inc.
Low-profile, 96-well
deep-well plate
Porvair Sciences
Combining an affordable price with
uncompromising high quality, Porvair
low-profile, 96-well deep-well plates are
precisely manufactured to comply with
ANSI/SLAS dimensional standards,
ensuring complete compatibility with all
automated sample handling systems,
microplate readers and washers.
Complementing the low-profile plate,
Porvair also offers a matching antievaporation cap mat, manufactured
from thermoplastic elastomer, to ensure
the long-term integrity of your stored
samples.
www.porvair-sciences.com
Horizon launches
gene-engineered
bioproduction cell line with
flexible licensing model
Horizon Discovery
Seahorse Bioscience
ships XFp Extracellular
Flux Analyzers to first
50 customers
Seahorse Bioscience
Seahorse Bioscience, the industry leader
in metabolic analyzers and assay kits for
measuring real-time cell metabolism, has
announced that the XFp Extracellular
Flux Analyzer is now shipping. U.S.
customers include the University of
North Carolina, National Institutes of
Health, Stanford University and Alexion
Pharmaceuticals. European customers
include the Karolinska Institute in
Sweden, Universitatsklinikum Muenster
in Germany and KU Leuven in Belgium.
The easy-to-use, compact and affordable
XFp Analyzer is the most recent addition
to the Seahorse line of metabolic
analyzers.
www.seahorsebio.com
Highly efficient neuro
transfection reagent
AMSBIO
Highly versatile
single-tube code reader
Micronic
The Tracxer Code Reader TS201 MINI
is high-speed storage tube codereading at its best. Attractively
designed to enhance your lab space,
the Tracxer TS201 MINI is truly
versatile—it reads 1D rack barcodes,
1D barcoded tubes and 2D Data Matrix
coded tubes (in 96-, 48- and 24-well
formats), all in less than a second.
www.micronic.com
AMSBIO announces DNA-In Neuro, a
new-generation transfection reagent
developed specifically for maximum
nucleic acid delivery into neurons,
typically achieving a twofold or greater
improvement in efficiency over currently
available competing reagents. DNA-In
Neuro Transfection Reagent offers
researchers a cost-effective, robust and
easy-to-use DNA delivery solution for
transfecting freshly isolated and
cryopreserved neurons. DNA-In Neuro
Transfection Reagent reproducibly
transfects neurons and neural stem cells
at optimal efficiency with exceptionally
low toxicity to support uncompromised
post-transfection assays.
www.amsbio.com
Horizon Discovery has shipped its first
commercially available engineered CHO
cell line for use in manufacturing of
therapeutic antibodies. Horizon’s
innovative licensing model brings these
cutting-edge bioproduction cells within
reach of companies of all sizes,
reducing timelines and costs associated
with the development of large-molecule
drugs (biotherapeutics). This latest
development is the first step in Horizon’s
strategy toward building a
comprehensive Good Manufacturing
Practice bioproduction cell line
platform.
www.horizondiscovery.com
BioTek introduces
second-generation
Cytation imaging reader
BioTek Instruments Inc.
Cytation 5 is a modular, upgradable
multimode reader that combines
automated digital microscopy and
conventional microplate detection.
Cytation 5 includes both filter- and
monochromator-based detection; the
microscopy module provides up to 60x
magnification in fluorescence,
brightfield, H&E and phase contrast.
Incubation to 65°C, shaking and Gen5
software are standard.
www.biotek.com
Q&A:Q&A
Lois Byra
of Alliance Life Sciences Consulting Group
For more information, visit www.DDN-News.com
JANUARY 2015 | | DDNEWS 39
Taking a look at contracting and pricing
L
DDNews: Describe how formulary codes work
and why and how they can be problematic.
BY LLOYD DUNLAP
OIS BYRA IS VICE PRESIDENT OF CONTRACTING,
strategy and compliance with Alliance Life
Sciences Consulting Group. With more than 15
years of experience in the life-sciences industry,
she has developed and implemented solutions
that deliver operational efficiencies across the organization.
Leveraging her IT background and business acumen in the
commercial and government contracting space allows her
to advise clients on appropriate solutions to their business
problems. DDNews asked Byra to help clarify compliance
issues as they now stand.
DDNews: How would you define or describe
the managed markets division of a
pharmaceutical manufacturer?
DDNews: What exactly are rebate
payments and what role do they play in
the overall system?
Lois Byra: The managed markets division of
Byra:
a pharmaceutical manufacturer is comprised
of groups that are involved in ensuring the
commercial access of a product, including
national and regional sales teams, marketing, and contract operations teams. Managed markets divisions contract with various
entities in order to ensure that products are
commercially available to patients through
reimbursements to wholesalers, pharmacy
benefit managers (PBMs), managed care
organizations (MCOs), group purchasing
organizations (GPOs) and government programs, such as Medicare and Medicaid—just
Rebate payments describe the flow of
cash from the manufacturer to any customer
that is contractually or legally eligible for a
reimbursement on a pharmaceutical product.
The managed care rebate payments are
calculated in the revenue management system
based on data provided by MCOs or PBMs, the
contracts configured within the system that
determine the eligible rebate percentages
and the wholesaler acquisition cost (WAC)
of a particular drug. A rebate percentage, for
example, can be based on the formulary tier
of a product on a health plan—meaning that
those products on a more advantageous tier
Lois Byra, Alliance Life Sciences
Consulting Group
DDNews: How important are Medicaid contracts?
Byra: Medicaid contracts and rebates, while
administered separately from other reimbursement mechanisms, are heavily dependent upon other areas of a manufacturer’s
business. The rebates given to the states
on Medicaid contracts are determined by
government pricing calculations, which
are in turn derived from aggregated commercial sales data. While participation is
voluntary, the terms of the agreement are
standardized across all manufacturers.
Involvement in the Medicaid program also
mandates an agreement with the Section
340B Drug Pricing Program and the Federal
Like prior legislation, the Affordable Care Act poses new stipulations for
the program, and therefore changes to how the contracts must be managed.
New segments of the population are covered based on changes to the
minimum percentage threshold of the federal poverty level required for
eligibility. Many states manage this by submitting rebates under “Medicaid
extension” contracts, which must be handled in tandem by manufacturers
along with the original contracts.
to name a few. Specifically, in the “Silos to
Synergy” white paper, we are focusing on
those that deal with reimbursements to
PBMs and MCOs.
DDNews: How do contact management,
rebate processing and government pricing
teams interact? Who does what?
Byra: Contract management teams negotiate the contracts between the manufacturer and the wholesalers, GPOs, MCOs
and PBMs. The rebate processing group
calculates the reimbursement these customers are eligible for based on the negotiated
contracts. The government pricing team
then utilizes certain data from the manufacturer’s direct and indirect sales, as well
as the rebate payments, to play a part in
determining price points required for provision to the government.
receive a higher rebate percentage—or by the
market share achieved during a certain period
in a particular therapeutic class. In the case of
wholesaler and/or GPO fees, although contract
structures vary, rebate percentages are usually
calculated based on variables of direct and/or
indirect sales, and WAC or contract price.
DDNews: Please describe the importance
of MCOs and PBMs in the overall revenue
management system.
Byra: Within the revenue management
system, MCOs and PBMs are customers that
are eligible for managed care rebates. These
customers all have unique contracts with
the manufacturer, and it is crucial that the
revenue management system is configured
based on their contracts. Improper or
inefficient setup can lead to incorrect rebate
payments or late fees.
For some customers, formulary codes
are embedded in the utilization file that is
provided to the manufacturer by the MCO or
PBM. These files are submitted in a set format that is predetermined in the contract and
encompasses all of the necessary information
the manufacturer needs in order to calculate
the rebate payment. For those contracts with
multiple formulary tiers, and therefore different rebate percentages, a formulary code
provides a unique field within the data that the
system can be set up to read to determine the
proper formulary for that particular transaction. In the event that the customer does not
submit a formulary code within the utilization
files, most revenue management systems have
ways of configuring a setup within the system
based on another field in the data. This, however, can become problematic in the event
that a health plan shifts tiers from one period
to the next. At times, the management of these
formularies within the system is extremely
cumbersome and requires significant upkeep.
A formulary code within the utilization file
removes the need for this maintenance.
Byra:
Supply Schedule. Concurrently, the entities reimbursed under these government
programs must maintain mutual exclusivity from those covered under the Medicaid
program and its extensions. Unlike managed
care, where rebates are provided to customers as purchase-based incentives, Medicaid
rebates serve the purpose of lowering the
net costs for program administration within
each state, thereby allowing the drugs to be
provided at a bare minimum of expense to
the covered individual. As such, the manufacturer does not see much profit from
Medicaid utilization. Rather, the program
allows a manufacturer’s drugs more ubiquity through access to a wider area of care
settings and formularies. Choosing not to
participate limits the overall extent of the
manufacturer’s portfolio.
DDNews: What impact, if any, will the
Affordable Care Act have on pharmaceutical
manufacturers and the role played by Alliance
Life Sciences Consulting Group and others?
Byra: While Medicaid contract terms cannot
be negotiated between the government and
the manufacturer, the guiding regulations
have evolved throughout the years, from
OBRA ‘90 and ‘93 to the Deficit Reduction
Act of 2005. Like prior legislation, the
Affordable Care Act poses new stipulations
for the program, and therefore changes to
how the contracts must be managed. New
segments of the population are covered based
on changes to the minimum percentage
threshold of the federal poverty level
required for eligibility. Many states manage
this by submitting rebates under “Medicaid
extension” contracts, which must be handled
in tandem by manufacturers along with the
original contracts. The act also required
that utilization through Medicaid MCOs
be submitted quarterly to manufacturers
in addition to traditional Medicaid feefor-service rebates, increasing the amount
of time and resources required to process
invoices. Significant changes were effected
for calculations of and regarding the average
manufacturer price (AMP), on which
Medicaid rebate levels are partially based.
Most critically, the Centers for Medicare
and Medicaid Services proposed two distinct
methodologies for AMP calculation based on
sales in retail and non-retail classes of trade.
However, the defining line for exclusion or
inclusion within these categories is not spelled
out with absolute precision. Furthermore,
as of now, the rule is only “proposed” and a
final one is still in the making. This lack of
specificity leaves room for interpretation as
manufacturers try to establish best practices
regarding these calculations, which Alliance
Life Sciences helps to implement. n
EDITCONNECT: E011529
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