Download MMRF and Inflection collaborate on new cancer

PHARMA, BIOTECH & LIFE SCIENCE
WHAT’S INSIDE
DISCOVERY6
RESEARCH & DEVELOPMENT
12
PRECLINICAL17
CLINICAL TRIALS
28
DIAGNOSTICS33
BUSINESS & GOVERNMENT POLICY
36
TOOLS & TECHNOLOGY
Optibrium integrates NextMove algorithm.......................8
Catalent, Sanofi collaborate on SMARTag, ADCs.........14
Agilent tool enhances integrity
of genomics experiments...................................................16
Optimizing trials through mobile health technology......32
On the cutting edge.............................................................38
FINANCE/MARKETS3
EDITORIAL/COMMENTARY10
LATE-BREAKING NEWS
42
AWARDS & HONORS
43
PRODUCTS & SERVICES
44
PEOPLE & PROMOTIONS
45
Q&A46
SHOW PREVIEW
AACR Annual
Meeting 2015
22
American Association for Cancer
Research brings the world’s
largest oncology research
conference to Philadelphia
MARCH 2015 : VOLUME 11 : NUMBER 3
PUBLISHED SINCE 2005
03.15
MMRF and Inflection collaborate
on new cancer treatment
Current focus is on
preclinical testing of
innovative dualmechanism PIM/PI3K
inhibitor IBL-202
BY JEFFREY BOULEY
DUBLIN & NORWALK, Conn.— Inflec-
tion Biosciences Ltd., a private company
developing what it calls “highly innovative”
treatments for cancer, announced in February a collaboration with the Multiple Myeloma
Research Foundation (MMRF) on preclinical testing of its dual-mechanism PIM/PI3K
inhibitor IBL-202. PIM and PI3K are two key
regulators in signaling pathways that have
proved essential for the proliferation and
survival of myeloma cells.
The MMRF investigators will test the
effectiveness of IBL-202 alone and in combination with other therapeutics in preclinical models of multiple myeloma. These
models are recognized to be predictive of
clinical efficacy in cancer patients with multiple myeloma. IBL-202’s dual-mechanism
MMRF CONTINUED ON PAGE 21
Inflection Biosciences and the Multiple Myeloma Research Foundation are pursuing preclinical
studies of a compound that targets two key regulators in signaling pathways that have proved
essential for the proliferation and survival of myeloma cells.
Roaring back…but more modestly
Pfizer makes first M&A
deal since failing to land
AstraZeneca, committing
to $17 billion for Hospira
BY JEFFREY BOULEY & LLOYD DUNLAP
least one thing that Pfizer shared in common with Valeant Pharmaceuticals last
year: going all-in with a huge takeover offer
for a major company ($117 billion offered
by Pfizer for AstraZeneca and $54 billion
offered by Valeant for Allergan), and ultimately failing in that bid. And, much like
Valeant (see story on page 42 for more on
that), Pfizer is confidently getting back on
the saddle in recent weeks with a smaller
but still multibillion merger and acquisition
(M&A) agreement—in this case, a $17-billion dollar deal under which Pfizer will buy
Hospira Inc.
The two companies announced Feb. 5
that they have entered into a definitive
merger agreement under which Pfizer
will acquire Hospira, a leading provider of
injectable drugs and infusion technologies
CREDIT: BUSINESS WIRE
NEW YORK & LAKE FOREST, Ill.—There’s at
Pfizer hopes to boost its injectable drug pipeline and biosimilars pipeline with the recently
announced acquisition of Hospira. Pictured here is a lab worker at Pfizer’s new Kendall
Square R&D facility in Cambridge, Mass., which was established in June of last year and
focuses on such therapeutic areas as inflammation and remodeling, immunoscience, rare
diseases, cardiovascular and metabolic disease and neuroscience.
and a global leader in biosimilars, for $90
per share in cash.
“The proposed acquisition of Hospira
demonstrates our commitment to prudently deploy capital to create shareholder value
and deliver incremental revenue and EPS
[earnings per share] growth in the near
term,” said Ian Read, chairman and CEO
of Pfizer. “In addition, Hospira’s business
aligns well with our new commercial structure and is an excellent strategic fit for
our Global Established Pharmaceutical
(GEP) business, which will benefit from
a significantly enhanced product portfolio
in growing markets. Coupled with Pfizer’s
global reach, Hospira is expected to drive
greater sustainability for our GEP business
over the long term.”
This “strategically complementary” combination will add a growing revenue stream
and a platform for building up Pfizer’s
GEP business. The expanded portfolio of
sterile injectable pharmaceuticals includes
acute care and oncology injectables, with
a number of differentiated presentations,
as well as a biosimilars portfolio that is
expected to reinforce GEP’s growth strategy
to build a broad portfolio of biosimilars in
Pfizer’s therapeutic areas of strength.
“The addition of Hospira has the
potential to fundamentally improve the
growth trajectory of the Global Established
Pharmaceutical business, vault it into
a leadership position in the large and
growing off-patent sterile injectables marketplace by combining the specialized
talent and capabilities of both companies,
including enhanced manufacturing, and
advance its goal to be among the world’s
most preeminent biosimilars providers,”
said John Young, GEP group president.
HOSPIRA CONTINUED ON PAGE 41
EVERY CANCER
TELLS A STORY
IF YOU HAVE THE
TOOLS TO READ IT
© 2015 PerkinElmer, Inc. 400311_05. All rights reserved. PerkinElmer® is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners.
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FINANCE
For more information, visit www.DDN-News.com
MARCH 2015 | | DDNEWS 3
G1 Therapeutics raises $33 million in Series B round
RESEARCH TRIANGLE PARK, N.C.—
In early February, G1 Therapeutics
Inc., a clinical-stage pharmaceutical company developing smallmolecule therapies to address
significant unmet needs in oncology, announced the completion of
a $33-million Series B financing
round. Lead investors Eshelman
Ventures and RA Capital Management were joined by new investors
Lumira Capital and Boxer Capital
of Tavistock Life Sciences, as well
as the company’s existing investors
Hatteras Venture Partners, MedImmune Ventures and Mountain
Group Capital.
As part of all this, Dr. Fred Eshelman, founder of Eshelman Ventures,
and Dr. Peter Kolchinsky, managing
Vaxxas raises
$20 million to
accelerate
vaccine
platform
general partner of RA Capital, have
joined G1’s board of directors.
G1 plans to use the proceeds to
advance its lead program, G1T28, a
highly potent and selective CDK4/6
inhibitor, through proof of concept
as an antineoplastic agent and as
a bone marrow chemoprotectant.
G1T28 is currently being evaluated in Phase 1a clinical trials to
assess safety, pharmacokinetics
and pharmacodynamics in healthy
volunteers. Data collected from
this study will inform the dose and
schedule for multiple Phase 1a/b
clinical trials in cancer patients,
which are expected to begin in
2015.
“This financing from new and
existing investors is a testament
to G1T28’s potential in multiple
oncology indications,” said Dr.
Mark Velleca, CEO of G1. “We’re
especially fortunate to have Fred
and Peter on our board, as their
business acumen and scientific
expertise will be invaluable as we
advance G1T28 through the clinic.”
“Rarely does an entirely novel,
orthogonal mechanism emerge
in oncology that has the ability
to combine with other approaches,” noted Kolchinsky. “There are
many inhibitors of angiogenesis,
immune evasion, DNA replication
and growth signaling. Shutting
down the G1/S cell cycle transition via precise CDK4/6 inhibition is now emerging as a category
unto itself, and G1 Therapeutics
is the only small company with a
selective agent in the clinic. While
three pharmas are ahead and have
done much to validate this class, we
expect significant interest from the
many others that already appreciate—or soon will—that they have
a gap in their toolkit.” n
Break free from qPCR
Find gene targets faster
BRISBANE, Australia—Vaxxas, a bio-
technology company commercializing a novel vaccination platform,
announced recently that it has
secured equity funding of A$25 million (approximately $20 million in
U.S. dollars) from new and existing
investors. The company’s corporate
offices are in Australia, but its global
partnering and licensing operations
are in Cambridge, Mass.
These funds represent the first
closing of a Series B venture financing round, the proceeds from which
will be used to advance a series of
clinical programs and develop a
pipeline of new vaccine products
for major diseases using Vaxxas’
patented Nanopatch platform. This
new round of financing brings the
total capital raised by Vaxxas to
A$40 million (about $33 million).
“As we have advanced the development of our Nanopatch needlefree vaccination technology, we have
seen tremendous opportunities to
create our own proprietary pipeline
of Nanopatch-based vaccine products, as well as those with partners,”
said David L. Hoey, president and
CEO of Vaxxas. “This funding creates an important inflection point
for Vaxxas, as we are now poised to
create significantly increased value
through our first clinical studies.”
Vaxxas’ proprietary Nanopatch
platform induces robust immune
system activation by targeting a
vaccine to the abundant immunological cells immediately below
the surface of the skin. Vaxxas’
plans call for applying its patented
needle-free vaccination technology against major diseases such as
influenza, polio, bacterial infections and cancer. n
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Biology for a better world.
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3/2/15 11:33 AM
MARKETS
4 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
Pharmaceutical and biotech market indices
O
Biotechnology Index
n feb. 24, 2015, the S&P 500 Health Care
Sector Index ended the day at 835.99,
down 0.06 percent but having advanced
by 5.44 percent in the previous three
months. Overall that day, the NASDAQ
Composite ended up 0.14 percent, the Dow Jones Industrial
Average rose by 0.51 percent and the S&P 500 closed with
a gain of 0.28 percent. Advances were broad-based, with
nine out of 10 sectors ending the session in the positive.
2736
2374
14/Mar
11/Apr
2505
09/May
2707
13/Jun
2794
11/Jul
2911
15/Aug
3082
3018
12/Sep
17/Oct
3254
3421
14/Nov
12/Dec
535
532
14/Nov
12/Dec
3523
3715
16/Jan
13/Feb
553
557
16/Jan
13/Feb
SOURCE: NYSE ARCA
Mini-pharma and Mini-biotech Indices
127
99
14/Mar
146
154
151
135
140
101
103
105
101
106
99
09/May
13/Jun
11/Jul
15/Aug
12/Sep
17/Oct
119
125
96
11/Apr
MINI-BIOTECH
171
163
Pharmaceutical Index
186
181
495
107
106
111
14/Nov
12/Dec
16/Jan
505
512
522
09/May
13/Jun
11/Jul
481
506
530
497
111
13/Feb
14/Mar
M I NI-PHAR MA
SOURCE: NYSE ARCA
11/Apr
15/Aug
12/Sep
17/Oct
SOURCE: NYSE ARCA
THREE THERAPEUTIC MARKETS POISED TO GROW
BY JEFFREY BOULEY
NEW YORK & LONDON—For GBI Research
and GlobalData, as they gaze into their financial crystal balls, colorectal cancer (CRC),
irritable bowel syndrome (IBS) and Cushing’s syndrome (CS) all show up as markets
to watch for gains—though not all of them
hold spellbinding potential.
From GBI comes a prognostication that the
CRC therapeutics market will increase moderately, from $8.3 billion in 2013 to $9.4 billion by 2020, representing a compound annual growth rate (CAGR) of just 1.8 percent.
The company’s latest report states that
this growth, which will occur across eight
major developed countries—the United
States, United Kingdom, France, Germany,
Spain, Italy, Japan and Canada—will be limited by the patent expirations of Avastin and
Erbitux during the forecast period, which
will prompt the uptake of lower-priced biosimilar versions of these drugs.
However, Saurabh Sharma, senior analyst
for New York-based GBI Research, says that
despite its patent expiration, Avastin is expected to retain its market-leading position in the
global CRC space through to 2020, explaining, “Avastin is heavily prescribed in both
first- and second-line settings, regardless of
the patient’s KRAS status. Its dominance is
consistent across both the metastatic KRAS
wild-type and mutation-positive settings,
despite the availability of epidermal growth
factor receptor inhibitors for the treatment of
KRAS wild-type disease. Additionally, Stivarga
is expected to be one of the biggest drivers of
growth in the CRC market, due primarily to its
anticipated line extension as a maintenance
treatment in the first-line metastatic setting
for patients with resected liver metastases.”
The predictions are more dramatic for IBS
and CS from the market-watchers for GlobalData in London.
According to the firm, the global therapeutics market for IBS is set to rise in value from
$589.6 million in 2013 to $1.5 billion by 2023,
representing a CAGR of almost 9.9 percent.
This expansion will be driven primarily by rising IBS prevalence, GlobalData says, along with
the increasing uptake of Linzess in the United
States, United Kingdom, France, Germany,
Italy and Spain. Linzess’ anticipated launch in
P
U
B
L
I
C
C O
M
BioCryst announces Q4 and full year
RESEARCH TRIANGLE PARK, N.C.—BioCryst
Pharmaceuticals Inc. recently
announced financial results for the fourth quarter and full year ended Dec.
31, 2014, with President and CEO Jon P. Stonehouse saying, “We are proud
of our 2014 achievements, most notably our successful completion of the
BCX4161 OPuS-1 trial and the initiation of OPuS-2 for the treatment of
hereditary angioedema (HAE), as well as our first U.S. regulatory approval
of a BioCryst-discovered drug, Rapivab for the treatment of acute uncomplicated influenza in patients 18 years and older. We have also made substantial progress in our second-generation kallikrein inhibitor program and are
now preparing BCX7353 to enter Phase 1 testing as a potential once-daily
oral treatment to prevent HAE attacks.”
In the fourth quarter, total revenues decreased to $5.4 million from $10.6
million in the fourth quarter of 2013, and research and development expenses increased to $18.5 million from $15.5 million.
Fluidigm reports financials
SOUTH SAN FRANCISCO, Calif.—Fluidigm
major driver behind the significant growth
in the CS therapeutics arena, along with the
arrivals of Novartis’ Signifor LAR in the six
major markets (United States, France, Germany, Italy, Spain and the United Kingdom)
in 2018 and HRA Pharma’s Ketoconazole
HRA (ketoconazole) in Europe in 2015.
Shaan Thakerar, GlobalData’s analyst covering cardiovascular and metabolic disorders,
says, “Additionally, the U.S. launch of secondgeneration steroidogenesis inhibitors, such
as Cortendo AB’s NormoCort (COR-003) and
Novartis’ LCI699, will also boost the market
over the forecast period.” n
Japan in 2017 will further boost the market.
Linzess faces competition from Amitiza
and the potential introduction of two additional IBS-C products, plecanatide and tenapanor, acknowledges Dr. Toli Koutsokeras,
GlobalData’s senior analyst covering immunology, but GlobalData still expect the drug’s
uptake to rise by 2023.
Meanwhile, the global CS treatment market will expand rapidly in value from approximately $179 million in 2013 to $499 million
by 2018, representing an impressive CAGR of
22.74 percent, predicts GlobalData.
Increasing disease prevalence will be a
Corp. announced its financial results
for the fourth quarter and full year ended Dec. 31, 2014, noting that total
revenue for the fourth quarter of 2014 was $33.5 million, an increase of 60
P A
N
Y
N
E
W
S
percent from $20.9 million in the fourth quarter of 2013. Organic revenue for
the fourth quarter of 2014 (excluding revenue attributable to the DVS Sciences acquisition, comprised of the CyTOF 2 system and proteomics analytical consumables) was $25.2 million, an increase of 21 percent from $20.9
million in the fourth quarter of 2013. Total revenue for the full year of 2014
was $116.5 million, an increase of 64 percent from $71.2 million in 2013.
Organic revenue for the full year of 2014 was $95.9 million, an increase of
35 percent from $71.2 million in 2013.
Net sales down for Genmab’s Arzerra
COPENHAGEN, Denmark—On Feb. 4, Genmab A/S announced that net sales of
Arzerra (ofatumumab) during the fourth quarter of 2014 were about $17.6
million. Under the terms of its collaboration with GlaxoSmithKline, Genmab
expects to receive a royalty payment of approximately $3.5 million. Full-year
2014 net sales of Arzerra totaled about $84.4 million worldwide, compared
to about $116 million in 2013. The total royalty income to Genmab for 2014
is approximately $15.4 million. During the second half of 2014, sales of
Arzerra were impacted by sales related to the supply of Arzerra for clinical
trials run by other companies. Sales were not impacted by clinical trial material sales during the first half.
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DISCOVERY
‘Wake-up’ pills for cancer immunotherapy
BR IEFS
CGEN-15049 results
presented at Keystone Symposia
Curis and Aurigene stretch
hands across the sea to
jointly discover, develop and
eventually commercialize
pills to fight cancer
TEL AVIV—The head of Compugen Ltd.’s immunol-
ogy group, Dr. Arthur Machlenkin, recently presented new experimental results for CGEN-15049,
a novel immune checkpoint protein discovered by
Compugen as a potential cancer immunotherapy
target. The data demonstrate expression of this
protein on tumors isolated from ovarian cancer
patients, both on the cancer cells themselves and
on immune cells in the tumor, as well as expression of CGEN-15049 on a population of tumor-infiltrating immune cells in mouse models. The data
also support the ability of this protein to affect
key components of the immune system known to
play a role in anti-tumor immune responses. The
studies that provided those data examined the
protein’s expression on cells isolated from primary
tumors of ovarian cancer patients. CGEN-15049
has been shown to be expressed on a number of
cancers, including ovarian, lung, breast, colorectal, gastric, prostate and liver cancers.
BY LORI LESKO
LEXINGTON, Mass.—Imagine a day when
cancer patients no longer suffer through
bouts of chemotherapy and radiation, a day
when cancer is treated—and cured—with
pills purchased at the local pharmacy.
That day is not far off, according to Dr.
Ali F. Fattaey, president and CEO of Curis
Inc., a biotech focused on the development
and commercialization of new targets to treat
cancer. Curis has teamed up with Bangalore,
India-based Aurigene Discovery Technologies Ltd., a specialized, discovery-stage biotech developing novel therapies to treat cancer and inflammatory diseases, entering into
an exclusive collaboration agreement focused
on immuno-oncology.
Together, the two biotechs have ratified
a two-year agreement worth an initial $190
million to take two small-molecule targets
through development and into the market.
HemoShear, Pfizer
ink DIVI collaboration
IN THIS SECTION
Compound optimization
Optibrium integrates
NextMove algorithm................................. 8
Oncology
CGEN-15049 results presented
at Keystone Symposia............................... 6
Investigating immunocytokines................. 6
‘Wake-up’ pills for cancer
immunotherapy.......................................... 6
Parkinson’s disease
Trash pickup problem................................ 6
Vascular injury
HemoShear, Pfizer ink DIVI collaboration... 6
“We are thrilled to partner with Aurigene
in seeking to discover, develop and commercialize small-molecule drug candidates
generated from Aurigene’s novel technology,
and we believe that this collaboration represents a true transformation for Curis that
positions the company for continued growth
in the development and eventual commercialization of cancer drugs,” Fattaey stated
in a news release.
“The multiyear nature of our collaboration
means that the parties have the potential to
generate a steady pipeline of novel drug candidates in the coming years,” he said.
The concept of using the body’s own
immune system to fight off disease is not
new, Fattaey tells DDNews. “But what we
have done for the first time is bring the use
of small-molecule oral drugs to wake up
each cancer immunotherapy,” he explains.
Dr. Mark Hannink and
colleagues at the
University of Missouri
(pictured here) believe
that a drug based on
the PGAM5 pathway
could be useful in
restoring
mitochondrial
recycling in certain
cells, like neurons
affected in
Parkinson’s, while
blocking this recycling
pathway in other
cells, like cancer cells.
CREDIT: UNIVERSITY OF MISSOURI
CHARLOTTESVILLE, Va.—A multiyear platform collabo-
ration is now underway between HemoShear and
Pfizer Inc., under which the former will apply its
proprietary discovery platform in pursuit of developing a predictive model for preclinical drug-induced
vascular injury (DIVI). No financial terms were disclosed. The initial phase will allow the partners to
recreate the drivers of DIVI biology in the lab with
HemoShear Translational Tissue Systems. Currently,
no generally accepted, specific diagnostic or predictive biomarkers exist to determine when or why DIVI
occurs, nor are there models to choose the safest
compound prior to animal testing.
“The overall goal of the collaboration is to
develop robust biological criteria and associated
computational tools to reliably identify and predict DIVI in animals and, ultimately, to elucidate
potential drug effects in humans,” said Dr. Brett
Blackman, co-founder and chief scientific officer
of HemoShear.
“What we have done for the first time is bring the use of smallmolecule oral drugs to wake up each cancer immunotherapy,” says
Dr. Ali F. Fattaey, president and CEO of Curis. “Technologically, it
allows us to go out and get an oral drug to treat cancer rather than
let patients and their families go through the effects of
chemotherapy and radiation.”
cells are functioning normally,
mitochondria—the “powerhouses” of cells—generate the necessary energy to keep cells alive.
When they become damaged and
unable to make energy, mitochon-
Investigating
immunocytokines
Kymab partners with industry expert for
more efficacious, tolerable therapies
BY KELSEY KAUSTINEN
dria are sent to a portion of the cell
called a lysosome to be repaired.
In the brains of Parkinson’s disease patients, mitochondria fail
to move to the lysosomes, causing accumulations of damaged
mitochondria that kill brain cells.
PEPTIDE CONTINUED ON PAGE 9
IMMUNO CONTINUED ON PAGE 8
Peptide could repair damaged mitochondria
to regulate Parkinson’s disease
COLUMBIA, Mo.—When brain
CURIS CONTINUED ON PAGE 7
CAMBRIDGE, U.K.—In the hopes of using its proprietary platform to develop new cancer therapeutic options, Kymab has
announced a collaboration with Dr. Stephen Gillies, a leader
in cancer immunotherapy who has invented promising immunocytokine platforms. Gillies is the founder and CEO of Provenance Biopharmaceuticals Corp. and is also on the board of
directors for Cambridge, Mass.-based Galenea Corp.
“I’m delighted to work with Kymab on development of novel
treatments, work that promises to produce improved products
for drug development in cancer. The program hits the ‘sweet
spot’ of our joint expertise and will be used to develop new and
transformational drugs in this fast-moving field,” said Gillies.
Kymab and Gillies will work together to develop new immunocytokine-based drugs that could exploit the synergistic potential
of combining antibodies directed against immuno-oncology drug
targets with the antitumor activity of certain cytokine molecules.
Steve Arkinstall, chief scientific officer of Kymab, says the company has licensed Gillies’ immunocytokine intellectual property
“as it relates to specific oncological drug targets.” Kymab will be
responsible for all experimental work while Gillies will act in an
advisory role for the project’s scientific and strategic direction.
The collaboration will focus on targets that could have potential
Trash pickup
problem
BY ILENE SCHNEIDER
“Technologically, it allows us to go out and
get an oral drug to treat cancer rather than
let patients and their families go through the
effects of chemotherapy and radiation.”
The collaboration with Aurigene “is very
exciting,” Fattaey says. “First, oral medication is efficient, less costly than chemo and
biologics, and you can still combine drugs to
design the medicine to treat each individual
cancer patient.”
Investigational New Drug (IND) application filings for both initial collaboration
programs are expected this year, and the
first trials will begin with human patients
this year, he said.
The Curis-Aurigene collaboration provides for the inclusion of multiple programs,
with Curis having the option to exclusively
license compounds once a development
DISCOVERY
For more information, visit www.DDN-News.com
CONTINUED FROM PAGE 6
candidate is nominated within
each respective program, according to the companies.
The partnership draws from
each company’s respective areas of
expertise, with Aurigene responsible for conducting all discovery
and preclinical activities, including
IND-enabling studies and providing Phase 1 clinical trial supply,
and Curis in charge of all clinical
development, regulatory and commercialization efforts worldwide,
excluding India and Russia, for
each program for which it exercises
an option to obtain a license.
The first two programs under
the biotech collaboration are an
orally available small-molecule
antagonist of programmed death
ligand-1 (PD-L1) in the immunooncology field and an orally available small-molecule inhibitor of
Interleukin-1 receptor-associated
kinase 4 (IRAK4) in the precision
oncology field.
Although several global Big
Pharma and biotech start-ups have
immunotherapy molecules, Aurigene has a completely different
class of them—peptides and peptidomimetics (molecules that mimic
peptides)—and says it is the only
company in the world developing
peptides against immune checkpoints, natural mechanisms that
cancers hijack to evade the immune
system.
Addressing immune checkpoint
pathways is now a well-validated
strategy to treat human cancers,
and the ability to target PD-1/PD-L1
and other immune checkpoints
with orally available small-molecule drugs has the potential to be
a major advancement for patients. Recent studies have also shown
that alterations of the MYD88 gene
lead to dysregulation of its downstream target IRAK4 in a number of
hematologic malignancies, including Waldenström’s Macroglobulinemia and a subset of diffuse large
B-cell lymphomas, making IRAK4
an attractive target for the treatment of these cancers. CSN Murthy, CEO of Aurigene,
stated, “We are excited to enter into
this exclusive collaboration with
Curis under which we intend to discover and develop a number of drug
candidates from our chemistry innovations in the most exciting fields of
cancer therapy. We have established
a large panel of preclinical tumor
models in immunocompetent mice
and can show significant in-vivo
antitumor activity using our smallmolecule PD-L1 antagonists. We are
also in the late stages of selecting a
candidate that is a potent and selective inhibitor of the IRAK4 kinase,
demonstrating excellent in-vivo
activity in preclinical tumor models.”
Aurigene, with its own internal
pipeline, works with established
pharmaceutical and biotechnology
companies in early-stage collaborations, bringing drug candidates
from hit generation through IND
filing. Aurigene has worked on
more than 40 partner targets over
the last nine years and has delivered
eight clinical candidates which are
in development by partners.
In connection with the transaction, Curis has issued to Aurigene
approximately 17.1 million shares of
its common stock, or 19.9 percent
of its outstanding common stock
immediately prior to the transaction, in partial consideration for
the rights granted to Curis under
Copyright Cisbio Bioassays. All rights reserved. All trademarks are property of Cisbio Bioassays.
CURIS
MARCH 2015 | | DDNEWS 7
the collaboration agreement. The
shares issued to Aurigene are subject to a lock-up agreement until
Jan. 18, 2017, with a portion of the
shares being released from the lockup in four equal biannual installments between now and that date. The agreement provides that
the parties will collaborate exclusively in immuno-oncology for an
initial period of approximately two
years, with the option for Curis to
extend the broad immuno-oncology exclusivity.
DISCOVER AN
EPIGENETICS ASSAY
PORTFOLIO YOU’LL
NEVER OUTGROW
Curis has agreed to pay Aurigene
up to $52.5 million per program
for the first two programs, including $42.5 million per program for
approval and commercial milestones, totaling $190 million. For
the third and fourth programs, the
figures are up to $50 million per
program, including $42.5 million
per program for approval and commercial milestones, and for any programs thereafter, up to $140.5 million per program, including $87.5
million per program in approval and
commercial milestones. For all programs, there would also be specified
approval milestone payments for
additional indications, if any.
Curis has agreed to pay Aurigene
royalties on any net sales ranging
from high single-digits to 10 percent in territories where it successfully commercializes products, and
will also share in amounts that it
receives from sublicensees depending upon the stage of development
of the respective molecules. n
EDITCONNECT: E031504
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DISCOVERY
8 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
Optibrium integrates NextMove algorithm
IMMUNO
CONTINUED FROM PAGE 6
StarDrop software suite will
incorporate Matsy algorithm,
which generates and
searches databases of
matched molecular series
BY ZACK ANCHORS
technologies are widely used in drug discovery have announced a collaboration that
could make it easier for scientists to quickly
identify novel, active compounds based on
matched molecular series analysis. Software
developer Optibrium has announced that the
latest version of its StarDrop software suite
will feature an integration with NextMove
Software’s Matsy algorithm, which generates
and searches databases of matched molecular series to identify chemical substitutions
that are most likely to improve target activity.
“Both Optibrium and NextMove realized that
Matsy and StarDrop were highly complementary and that a collaboration could bring
additional benefits to our users,” Roger Sayle,
NextMove CEO and founder, tells DDNews.
StarDrop is a software platform used in
the drug discovery process that was first
launched in 2005, when it was a product
of Inpharmatica. The core research group
behind the technology has worked together
since 2001 and founded Optibrium as a management buyout
in 2009 to focus on its development. The primary function
of the software is to facilitate
multiparameter optimization,
which involves guiding the identification of effective leads and assisting their
transformation into candidate drugs with a
high probability of success. The software features a highly visual and interactive interface
designed to make it easy for all members of
a project team to make decisions regarding
CREDIT: OPTIBRIUM
CAMBRIDGE, U.K.—Two companies whose
Optibrium’s StarDrop is a software platform used in the drug discovery process that was first
launched in 2005, when it was a product of Inpharmatica. It will now incorporate NextMove
Software’s Matsy algorithm.
compound selection and design.
NextMove’s Matsy algorithm grew out of
a collaboration last year with computational
chemists at AstraZeneca that
was designed to help researchers
make more informed decisions
during the lead optimization process. The goal of the project was
to create a tool that would help
medicinal chemists to identify
which compounds to prioritize after they
develop molecules and measure their biological activities. “Typically this decision is based
on the medicinal chemist’s experience with
related projects or based on their chemical
intuition,” Sayle tells DDNews. “In contrast,
TOOLS &
TECHNOLOGY
Matsy makes suggestions using a knowledge
base of experimental data.”
The data used by Matsy’s algorithm can
include either a company’s own in-house
database or a database such as ChEMBL that
contains experimental data on molecules
with drug-like properties extracted from
published literature. “The advantage of this
approach is that all predictions are backed
by experimental results which can be viewed
and assessed by the medicinal chemist when
considering the predictions,” says Sayle.
NextMove Software and Optibrium predict that integrating the Matsy technology
with StarDrop will provide researchers more
STARDROP CONTINUED ON PAGE 9
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against several types of cancer.
“This new collaboration with one of
the leading figures in immunocytokine
research offers an exciting opportunity to
develop new anticancer drug candidates,”
Arkinstall commented. “Our world-beating antibody discovery technology will
enable us to develop novel immunooncology drug candidates through leveraging the synergy of antibodies targeting
cancer cells fused to selected cytokines
localizing them to the tumor microenvironment. This in essence will give a
‘double-hit’ on cancer cells.”
Some cytokines demonstrate antitumor activity, but as is the case with
a number of chemotherapeutic drugs,
their therapeutic potential is hampered by their toxicity. As explained on
Provenance’s website, Gillies’ approach
uses a whole antibody format, in which
a cytokine is genetically fused to the
end of an antibody-heavy chain.
The effect this has depends on
both the cytokine that is used and
the type of immune cell, because “In
some cases, the effect is similar to a
bi-specific antibody when the cytokine acts as a trigger for an immune
effector cell leading to direct tumor
lysis, while in other cases it results
in immune cell activation and proliferation of tumor-specific T cells that
indirectly kill the tumor cells through
their own recognition molecules (T
cell receptors).”
“The benefits of immunocytokine
drugs is that they are able to leverage
the well-known anticancer therapeutic
activity of some cytokines (e.g. IL-2,
IL-12) while at the same time, minimizing the toxic side effects of these cytokines through targeting their activity
specifically to the tumor micro-environment,” Arkinstall explains. “It is
believed that high therapeutic benefit
may be achieved at significantly lower
doses than is achieved with approved
cytokine treatment regimens.”
For its part, Kymab’s Kymouse technology can rapidly generate a range of
fully human antibodies, offering highaffinity, candidate-quality molecules
that require no further lead optimization since the molecules “are already
optimized in vivo for affinity and biophysical properties,” the company
website asserts.
“Our search for new treatments
drives us to seek the best opportunities to move research forward towards
drug development,” Dr. Christian
Grøndahl, outgoing CEO of Kymab,
said in a press release. “This is a
biology-based, genome-driven, rational program that will use the power
of our understanding of the immune
system’s ability to combat cancer and
will feed new and exciting products
into our pipeline.”
“We are convinced that immunocytokine drugs, such as those emerging
from our collaboration with Dr. Gillies, have the potential to be an important part of a new and varied armory of
immuno-oncology-based treatments
for cancer,” Arkinstall adds. n
EDITCONNECT: E031506
For more information, visit www.DDN-News.com
DISCOVERY
MARCH 2015 | | DDNEWS 9
PEPTIDE
peptide did in the experiments.
“We don’t know if this will reverse
or stop Parkinson’s,” Hannink adds.
“That will need to be tested in animal models, as the next step. But
the idea is that by switching from
the PINK1/PARKIN pathway, which
is defective in some forms of familial Parkinson’s, to the FUNDC1
pathway, it might be possible to
bypass the defective pathway and
activate a compensatory pathway.”
Early-stage results of this
research look promising, accord-
CONTINUED FROM PAGE 6
STARDROP
CONTINUED FROM PAGE 8
powerful capabilities as they
search for the most promising
chemical substitutions. Unlike
the conventional approach of
relying on matched molecular
pair analysis, the Matsy algorithm uses data from longer
series of matched compounds,
rather than just pairs, to make
more relevant predictions for
a particular chemical series of
interest.
Matsy will be integrated into
StarDrop through the software
platform’s Nova module, which
automatically generates new
compound structures to stimulate the search for optimization
strategies related to initial hit or
lead compounds. The options
that result from this process
can then be analyzed using
StarDrop’s capabilities for multiparameter optimization and
predictive modeling so that highquality compounds with the best
EDITCONNECT: E031505
3292R DSC XP2_3.375x10_Layout 1 5/2/14 9:34 AM Page 1
CREDIT: RANDY MERTENS, CAFNR
The situation is what University of
Missouri (MU) researcher Dr. Mark
Hannink calls a “trash pickup problem,” as waste continues to be generated and not recycled or removed.
Hannink, a professor in the MU
Department of Biochemistry and
an investigator at the university’s
Bond Life Sciences Center, has discovered a molecule that could aid
mitochondrial recycling and keep
brain cells alive. This could help to
develop drugs to keep brain cells
healthy in individuals with Parkinson’s disease, as he reported in
“A conserved motif mediates both
multimer formulation and allosteric activation of phosphoglycerate
mutase 5,” recently published in the
Journal of Biological Chemistry. Peter
Tipton, MU professor of biochemistry, and graduate students Jordan
M. Wilkins and Cyrus McConnell
contributed to the research.
As Hannink explains, “Mitochondria eventually become damaged
and no longer function properly, so
the cell has a mechanism to recycle
them, keeping them strong. If that
recycling pathway doesn’t work, the
defective mitochondria will build
up and will disrupt cell physiology,
ultimately causing that cell to die.”
Parkinson’s disease is the clearest
example of this recycling failure.
“In early-onset Parkinson’s,
mutated proteins ‘forget’ to recycle
mitochondria, resulting in a buildup of toxic waste and early onset
of the disease,” he says. “In our
study, we found a peptide, or molecule, responsible for an alternative
pathway that bypasses the mutant
Parkinson’s proteins and allows
mitochondrial recycling. We feel
that this peptide could prove useful in fighting diseases in the brain.”
He adds, “The process that I am
ing to Hannink. If additional studies are successful within the next
few years, MU officials will request
authority from the federal government to begin human drug development. After this status has been
granted, researchers may conduct
human clinical trials with the hope
of developing new treatments for
Parkinson’s and other diseases.
“Commercial potential is sheer
speculation at this point,” Hannink
concludes. n
Pipet-Aid
XP2
Dr. Mark Hannink and Kim Jasmer (pictured here in a University of Missouri
photo from October 2014) worked to discover a molecule that treats
oxidative stress and could lead to therapies for cancer, Alzheimer’s and
Parkinson’s disease. In a more recent development, Hannink and colleagues
have discovered a molecule that could aid mitochondrial recycling and keep
brain cells alive in Parkinson’s patients.
looking at is not repair of damaged
mitochondria, but the removal/
disposal/degradation of damaged
mitochondria. This alternative
pathway for mitochondrial recycling uses a protein called phosphoglycerate mutase family member 5 (PGAM5). A peptide acts as
a ‘switch’ to cause the protein to
create an alternate pathway.”
By regulating the protein with
the peptide that Hannink discovered, it may be possible to restore
mitochondrial recycling in neurons
of patients with Parkinson’s, lessening the severity of the disease. He
thinks that development of a drug
based on the PGAM5 pathway
could be useful in restoring mitochondrial recycling in certain cells,
like neurons affected in Parkinson’s.
while blocking this recycling pathchance of success are identified.
Sayle tells DDNews that the
integration of Matsy and Stardrop, which the companies
began working on late last year,
is progressing quickly. He expects
a initial version of the technology
to be available for demonstration
at the American Chemical Society Spring National Meeting in
March, followed by a release for
users of StarDrop this year. The
Matsy technology will initially be
integrated into an updated version of StarDrop’s optional Nova
module, providing all current
users of the Nova module with
access to the extended capabilities. Sayle says the partnership
between his company and Optibrium could lead to further collaboration. “This is our first collaboration, and based on its success,
we hope to identify further areas
in which we can work together
going forward,” Sayle says.
NextMove, which was founded
in 2010, offers a range of other
chemoinformatics solutions for
way in other cells, like cancer cells.
“The PGAM5 protein would be
regulated by an allosteric mechanism, in which its biological function would switch from activation
of the PINK1/PARKIN pathway for
removal of damaged mitochondria
to the FUNDC1 pathway for removal
of damaged mitochondria,” according to Hannink. “Peptides behave
like drug molecules; any time you
can identify a biological process that
is regulated by a peptide, that peptide becomes a leading candidate in
the search for small, drug-like molecules that will act the same way.”
For Parkinson’s disease, the goal
is to find ways to repair the mitochondria recycling process. The next
step of the research is to produce a
drug molecule that can regulate the
PGAM5 protein in cells, just as the
pharmaceutical and chemicals
industries besides Matsy. The
firm’s product portfolio includes
LeadMine, a program used for
extracting chemical names and
terms from text such as patents;
HazELNut, a suite of tools used
to extract, normalize and analyze
information in electronic lab
notebooks; and Sugar & Splice,
a technology used for perceiving,
naming and depicting biopolymer structures.
“We are delighted to announce
our collaboration with NextMove
Software, which has a proven
track record of developing innovative informatics solutions for
pharma companies worldwide,”
said Matthew Segall, Optibrium’s
CEO. “We remain committed to
working with NextMove and our
other partners to provide access
to the leading compound optimization technologies through
StarDrop’s unique environment
that guides efficient discovery of
novel, high-quality drugs.” n
EDITCONNECT: E031507
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EDITORIAL
For more information, visit www.DDN-News.com
Out with the broad and in with the rare
A
In what BIO says is a first-of-its-kind study on
venture financing broken down by disease area
DDNews’ managing editor, Lloyd and novelty of research over a 10-year period
Dunlap, for his first editorial in from 2004 to 2013, encompassing $38 billion
these pages, I decided to run a of venture capital into more than 1,200 U.S.
drug companies that received more
piece on a new report,
than 2,000 rounds of funding, “The
“Transforming Rare Disease Patients’
aim was to identify funding trends
Lives Through Innovation” (both can
for emerging drug developers within
be found right next door on page 11)
specific therapeutic areas and across
to fill the remaining space, since
varying levels of innovation,” said Dr.
reports from industry organizations
Cartier Esham, BIO’s executive vice
are, in my mind, certainly a form of
president of emerging companies.
commentary themselves.
Two findings that struck me were
As I pondered what to write for
that disease areas affecting large
my own editorial this issue, I didn’t
populations—diabetes, psychiatry,
expect to be addressing a counter- Jeffrey Bouley,
DDNews Chief Editor
gastrointestinal, respiratory and
point to what one would think would
be only good news—after all, who doesn’t want cardiovascular—all have experienced a decline
to see rare diseases get attention? And, besides, in novel drug R&D venture funding, while rare
such treatments can be good business for phar- disease funding has seen a large increase over
mas and biotechs because while the patient the past decade in terms of both dollars raised
populations might be small, the price points for and number of companies funded.
In an article about the report, San Francisrare disease therapeutics can be quite attractive.
But a sort of counterpoint I did get, when by co Business Times reporter Ron Leuty quoted
chance I stumbled upon the very recent “Ven- OncoMed Pharmaceuticals Inc. President and
ture Funding of Therapeutic Innovation” report CEO Paul Hastings as saying venture capitalists
from the Biotechnology Industry Organization are more likely to invest in companies develop(BIO) that talks about venture funding and ing orphan disease treatments or cancer treatwhere it is—and isn’t—going these days. Appar- ments because those disease areas have wellently, rare diseases are getting the shine right tested pathways and are relative easy targets
now, and diseases that affect large populations compared to more general ailments that require
very large clinical trials and longitudinal studies.
are not.
BY JEFFREY BOULEY
H, SERENDIPITY. As we bring out
It would be easy to look at Hastings’ statement and say, “Of course; makes sense.” But
he’s not simply talking about a longstanding
venture capital preference. Because what BIO
has tracked is a trend toward the niche and away
from the broad.
This is certainly not alarming to me by any
means. While venture capital is important in
any market, and perhaps pharma and biotech
more than many, there are plenty of established
companies working on plenty of treatments and
vaccines for common diseases. And even with
flat funding and cuts over the years in government support and financial challenges for foundations, academic institutions get many grants
for innovative life-sciences research.
But at the same time, one of the other things
we’ve seen over recent years is a tightening of
the belts even in Big Pharma, and a resulting
constriction of R&D spending. So, increasingly,
some of the most interesting innovation we
see in big companies comes by way of smaller
companies they’ve partnered with or acquired—
companies that might not have existed at all
without venture funding.
No, I’m not worried about a significant
decline in therapeutics for large-population
disease areas. But I do feel a twinge of regret
that for the “attractive” needs of the few, the
more “banal” needs of the many may miss out
on some innovative treatment solutions in the
coming years. n
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OUT OF ORDER: THE VACCINE DE-BAIT
C
BY RANDALL C WILLIS
AN WE PLEASE STOP CALLING THE
vaccine controversy a debate?
This is not a debate. This is
two groups of people standing
atop their personal mountains
throwing unpleasant epithets and “evidence”
at each other.
On one mountain, you have scientists and
healthcare specialists throwing out statistics and
medical jargon and epidemiology. On the other
mountain, you have vaccine-cautioners showing
photographs of sick vaccinated children (and
correlating the two adjectives) and demands
for individual freedoms and the defense of their
child from potential harm.
Both sides are adamant about the absolute
truth of their positions, and therefore, there is
Unfortunately, the
Western world has become
incredibly risk-adverse and
benefit-demanding, and
this is where the statistical
nature of science and
healthcare runs up
against the individual
nature of health.
no point in discussion. The other side is either
willfully stupid or lying to push forward an agenda, so there is no point in discussion.
Unfortunately, I think if an actual debate was
held and, say, televised, science and healthcare
might come out with the short end of the stick.
Please note, before you read on, that I am provaccination (although please do not ask me the last
hear all the statistics they want,
time I was vaccinated for anything,
but show them a single photo of a
including the flu).
harmed child, and I can guarantee
It’s not that the facts aren’t
what direction they will lean. Having
there. It is rather that the facts are
worked in medical marketing, I have
largely indirect and require certain
seen it time and again.
assumptions.
“National measles vaccination proUnlike pretty much every other
grams effectively eradicated measles
category of therapeutic, patients do
in Canada and the United States,” a
not get better (e.g., an existing dishealth policy advocate may argue, but
ease condition relapses or is cured)
what does that really mean to a young
when they are vaccinated, but rather,
Randall C Willis
parent with no exposure (apologies)
they do not get sick. Or at least, we
assume they did not get the disease because they to measles. I’m 51 years old and I have never seen
were vaccinated. All we can truly measure is that anyone with measles who was more than itchy
they produced antibodies against the infectious and miserable.
In a recent commentary in The Toronto Star,
organism. True placebo-controlled experiments
would be unethical and might take decades to University of Toronto respirologist Sami Gupta
discussed the current vaccination challenge.
show statistical advantage.
“Studies show that didactic repetition of facts
Ah, but what about population statistics that
show how the introduction of widespread vac- just doesn’t change behavior, and that our topcination led to large-scale reductions in the inci- down and adversarial approach further polarizes
dence of the disease? I am woefully ignorant of communities and actually alienates parents.”
My marketing experiences suggest his comstatistics (really should be better at them, but
alas), but I don’t know that we can prove causa- ment is correct, but I also don’t think it goes
tion here, only be overwhelmed by the correla- far enough.
We talked about the idea of disease prevention (please correct me, if I am wrong).
And leaving aside any conversation about tion, but tended to gloss over the low-but-notautism (which I believe is baseless), the fact is zero risks of adverse events. Then, when the very
that all vaccines (as with all therapeutics) are rare adverse event does occur, usually with a
associated with experienced adverse events photo of a forlorn child, we are caught in a sin
(actual events, not just the risk of the event). of omission.
We talked about the power of herd immunity
While the rates of most of these events are
incredibly low, they are not zero. That is the and are now seeing that used as ammunition
nature of the risk-benefit analysis for any thera- against the vaccination of individuals. “If everyone else’s child is immunized, why should mine
peutic decision.
Unfortunately, the Western world has become have to be?”
Unfortunately, because of the unique format of
incredibly risk-adverse and benefit-demanding,
and this is where the statistical nature of sci- vaccines, I think we have to “stoop” to the level of
ence and healthcare runs up against the indi- the other side and focus on the risks of not vacvidual nature of health. A mother or father can
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EDITORIAL
MARCH 2015 | | DDNEWS 11
COMMENTARY: Candy
Land, opioid
addiction and help that’s on its way
R
BY LLOYD DUNLAP
ECENTLY, I discovered
that a Veteran’s Administration hospital (can’t
they do anything right?)
in Wisconsin has experienced a fourfold increase in opioid
use between 2005 and 2012 and earned the nickname Candy Land as a
result. Since I had just been assigned
the task of writing this, my first editorial for DDNews, and had covered
the subject of opioid addiction for
our Feb. Q&A feature, I thought I
would look into the issue further.
As Mark Sirgo, president and
CEO of BioDelivery Sciences Inc.
told our readers in the Q&A, there
are more than two million people
in the United States who were
dependent on opioids as of 2012,
according to the National Institute on Drug Abuse. There are five
different classes: 1) heroin, which
has no medical value; 2) morphine, oxycodon and hydrocodone;
3) buprenorphine, which is both an
agonist and antagonist and exhibits
a low propensity to develop a “high”
or craving; 4) antianxities such as
diazepam and alprazolam; and
finally, 5) cough syrup
ties. The low abuse
with codeine. Sirgo’s
potential of the new
company has developed
molecule may open new
a buccal patch that
avenues for the treatallows buprenorphine
ment of neuropathic
to be easily and quickly
pain, a chronic pain
absorbed to enhance
condition that can affect
bioavailability and
people after a stroke or
patient compliance.
with multiple sclerosis,
Dr. Eliseo Salinas
HIV infection, diabetes
notes that Relmada Lloyd Dunlap, DDNews and other conditions.
Managing Editor
Therapeutics, where
LevoCap ER: The
he is president and chief sci- Relmada research team is working
entific officer, has four pain meds to develop an extended-release,
in the pipeline—one of which is tamper-resistant form of levorpbuprenorphin—that collectively hanol for the treatment of chronic
reflect a diverse range of reformu- pain when an opioid is needed.
lation and repositioning strategies. Stronger than morphine, it was
Their efforts are targeting impro- created as its alternative more than
ved efficacy as well as reduced risk 40 years ago. There is great demand
of abuse and new drug delivery for extended-release formulations
technologies. Here’s an “executive for pain due to limited availability
summary” as Salinas describes it:
in the market today.
d-Methadone: Researchers at
MepiGel: Here they are working
Relmada have identified a process on a reformulation of the local anewhere they can separate out the “d” sthetic mepivacaine for the treatfrom the “l” isomer in methadone, ment of neuropathic pain (postheran NMDA (N-methyl D-aspartate) petic neuralgia and HIV-associated
agonist, to create a new molecule neuropathy). MepiGel is a topical
with the benefits of methadone that formulation that has U.S. Food and
may not have the addictive proper- Drug Administration Orphan Drug
designation. As a topical formulation, it may provide greater ease
of use and efficacy (skin penetration) for those with neuropathic
pain. There are no other topical gel
dosage forms for a local anesthetic
for the treatment of neuropathic
pain available today.
BuTab ER: Here the team is working
to develop an oral dosage form of the
opioid analgesic buprenorphine with
modified release and improved oral
bioavailability. All other forms of
buprenorphine are either injected,
use a patch or are sublingual, so
a successful repositioning of this
compound may make this the first
tablet available.
Timothy Lepak is president and
cofounder of the National Alliance
of Advocates for Buprenorphine
(NAABT), which is responsible
for www.treatmentmatch.org that
claims to have matched a total of
more than 82,000 patients with
28,000 doctors nationwide, only
about 10,000 of whom actually prescribe, he tells DDNews. The NAABT
Patient/Physician Matching System
is a centralized list of patients from
which certified physicians can draw
A decade of notable progress against rare diseases
WASHINGTON, D.C.—The Phar-
maceutical Research and Manufacturers of America (PhRMA)
released on Feb. 25 a new report,
“A Decade of Innovation in Rare
Diseases,” to document the significant progress made in the last
10 years in understanding a broad
range of rare diseases and translating this knowledge into groundbreaking therapies for a variety of
patient populations.
The report illustrates that more
than 230 new medicines to treat
rare, or orphan, diseases were
approved by the U.S. Food and
Drug Administration in the last
decade, and there are currently
more than 450 orphan drugs in
development.
It also explores significant
treatment advances seen over the
past decade in five rare diseases
which have led to improvements
in patient survival and quality of
life: chronic myelogenous leukemia (CML), chronic lymphocytic
leukemia (CLL), pulmonary arterial hypertension (PAH), hereditary angioedema (HAE) and cystic fibrosis (CF). Furthermore,
the report spotlights additional
rare conditions where major
milestones transformed treatment—including several in which
first-ever treatment options have
become available to patients.
Key findings include:
Targeted therapies can now
effectively treat many of the
recently identified mutated forms
of CML and allow for treatment
plans tailored to each patient’s
particular genetic profile.
Novel targeted therapies treat
the root cause of CLL, resulting in
lasting remissions and new treatment options for even the sickest
patients.
New treatments go beyond
symptom management to treat
the underlying cause of PAH,
allowing patients to maintain
active lifestyles with reduced risk
of serious heart events.
New discoveries in the underlying cause of HAE have led to
breakthroughs in both preventative and acute treatment options
for patients, including those targeting the root cause of the disease.
CF patients now have new
treatment options allowing for
better management of symptoms, as well as a new option
which allows many to target the
■■
■■
■■
■■
■■
underlying cause of their disease.
If mortality rates continue to
decline, patients may now hope
to live into their 50s.
“Rare diseases are one of the
most scientifically complex health
challenges we face,” said PhRMA
President and CEO John J. Castellani. “Over the last 10 years, biopharmaceutical researchers have
leveraged cutting-edge technologies and dramatically expanded
our understanding of rare diseases to develop new therapies for
chronic myelogenous leukemia,
cystic fibrosis and other diseases
which often impact very small
patient populations. We continue
to work toward options for rare
disease patients, where there may
currently be few or no treatments
available.”
The new report was released
ahead of Rare Disease Day, which
was celebrated Feb. 28, 2015. The
day is an opportunity for the
international rare disease community—including academia, patient
advocacy groups, pharmaceutical
and biotechnology companies,
research and regulatory government agencies—to collectively
educate and raise awareness about
rare diseases and their impact on
the lives of patients and their
families.
Thirty million Americans,
about one in 10, and an estimated 350 million people worldwide
are currently living with a rare
disease, which is defined as a
condition that affects fewer than
200,000 people. There are currently 7,000 known rare diseases,
and approximately 80 percent are
caused by genetic abnormalities.
However, despite incredible progress made against rare disease in
recent years, only 5 percent have
available treatment options.
While there remains a significant need to develop new medicines for patients, this is a challenging endeavor, PhRMA notes.
Rare diseases are often complex,
and the underlying biological
mechanisms that cause them are
not always well understood. Nevertheless, researchers continue
to build on recent breakthroughs
and are dedicated to bringing new
medicines to patients. With more
than 450 medicines in development to treat rare disease, the
promise has never been greater
for patients. n
when they have an opening.
Ideally, when a patient decides
he or she needs treatment, a phone
call is made to a physician on the
“Find a Certified Physician” list,
and the patient gets an immediate
appointment and is treated the next
day. However, there is a limit on
how many patients a doctor can
treat, which began at 30 per year
in year one and is now 100. The law
specifies that there must be three
societies who train physicians, but
Lepak points out that the training
is a mere eight hours.
The transition to buprenorphine
goes quickly, Lepak notes and can
be accomplished in only a few days.
“We’re not switching one addiction
for another,” he states. “It allows
people to get their lives back.”
As with many mental health
issues, there is help for those who
have the pluck to reach out for
it. And the research reported on
here indicates more help is on its
way. But if you persist, figuratively
speaking, in squeezing the trigger
on your morphine drip too often,
you may wind up like many of the
patients in Candy Land. n
ORDER
CONTINUED FROM PAGE 10
cinating, at a personal level. No
more statistics, no more history
lessons, but rather anecdotes
and photos of people with the
infectious diseases. Yes, it is
fear-mongering, but if we are
honest about our own limitations, then it is at least balanced
fear-mongering and is a starting point for a conversation
rather than a shouting match.
Later tonight (as I write this
column), the Canadian television news program The National
is convening a panel to discuss
the current vaccine conversation. I will be intrigued to see if
they actually include a so-called
“anti-vaxxer” on the panel to
make this a true debate, or if it
will be a panel of like-minded
healthcare specialists espousing
the official line—the “didactic
repetition of facts” about which
Gupta warned.
[Added note: The only place
I have seen an actual debate
on this topic was on The
Nightly Show with Larry Wilmore on Comedy Central, which
included a vaccine-cautioner
on its panel. Read into that
what you will.] n
The opinions expressed in guest commentaries do not necessarily represent those of DDNews and/or its owners, editors or other staff.
12 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
RESEARCH & DEVELOPMENT
STEVENAGE, U.K.—Plasticell got a boost in early
February with a grant of approximately £1.3 million
(roughly $1.5 million) from Innovate UK. The grant
is for a research consortium—one led by Plasticell
that also includes the University of Oxford and the
Cell Therapy Catapult—for a project titled “Exvivo expansion of cord blood and bone marrow
stem cells.” Plasticell’s CombiCult has been tested
with millions of combinations of cell culture components to develop cord blood expansion media
that can amplify stem cells up to a hundredfold,
and the grant will enable the development of a
clinically compliant process to expand cord blood
stem cells ex vivo via Plasticell’s media.
Cornell researchers create new
computational method
ITHACA, N.Y.—Scientists from Cornell University
have developed a computational method that
can identify positions in the human genome that
play a role in the proper functioning of cells, and
that work was published in Nature Genetics
Jan. 19. The new method utilizes two existing
techniques to identify selective pressure: one
that looks for divergences between human and
chimpanzee genomes, and another that looks for
polymorphisms between individual humans. The
new method clusters functionally similar genome
markers into groups, then estimates the probability of that group contributing to the fitness of the
species based on associated patterns of divergence and genomic polymorphisms. This generates a “fitness consequence” (fitCons) score that
predicts the genetic material that may be under
selective pressure and biologically significant.
Reportedly, fitCons scores have a much greater
power to predict genetic material that regulates
gene expression compared to existing methods.
IN THIS SECTION
Antibody-drug conjugates
Catalent, Sanofi collaborate on
SMARTag, ADCs...................................... 14
Antibiotic resistance
New ammo in arms race
against antibiotic resistance................... 12
Genomics
Agilent tool enhances integrity
of genomics experiments........................ 16
Cornell researchers create
new computational method.................... 12
Oncology
Taming the tsunami................................. 12
Stem cells
Plasticell awarded £1.3M
from Innovate UK..................................... 12
Tissue culturing
Onward and upward with organoids....... 12
Taming the tsunami Onward and
upward with
organoids
UCSD, UCSF launch Cancer
Cell Mapping Initiative
BY ILENE SCHNEIDER
SAN FRANCISCO & SAN DIEGO—The Univer-
sity of California, San Diego (UCSD) School
of Medicine and University of California,
San Francisco (UCSF), with support from a
diverse team of collaborators, have launched
an ambitious new project that may last 20
years and could make personalized medicine
a practical reality.
The Cancer Cell Map Initiative (CCMI)
has been created to determine how all of the
components of a cancer cell interact. It was
motivated by the “tsunami of genomic information available” in recent years, but the
inability to make sense of it, according to Dr.
Nevan Krogan, director of the UCSF division
of life-sciences research institute and accelerator QB3 and an investigator at Gladstone
Institutes. Krogan is also co-director of the
CCMI with Dr. Trey Ideker, chief of medical
genetics in UCSD’s Department of Medicine
and founder of the UC San Diego Center for
Computational Biology & Bioinformatics.
CCMI CONTINUED ON PAGE 13
Culturing techniques for
liver and pancreas
organoids can mirror
disease, cancerous states
BY KELSEY KAUSTINEN
Institutes of Health (NIH) that will assist the
researchers in developing new and improved
tools for studying the formation and structure of cell walls in bacteria, a line of resea-
UTRECHT, The Netherlands— The
promise of lab-grown tissues, especially organs, has captivated scientists
to a large degree
over the years.
Model organs,
also known as
organoids, could
offer a variety of
potential uses:
they can enable
researchers to
more accurately Prof. Hans Clevers,
test the toxic- professor of
ity of compounds molecular genetics
before risking at the Hubrecht
participants in Institute/UMC
human trials, Utrecht, and
colleagues recently
allow closer study announced the
of disease pro- development of a
gression and pos- culturing system
sibly represent a for liver stem cells
new solution to and stem cells
the great need for from pancreatic
transplant organs. cancer.
And a pair of papers featuring
research out of the Hubrecht Institute
and University Medical Center Utrecht
(UMC Utrecht) could offer a new avenue for exploring that potential.
This research began several years
ago when, in 2009, a research group
led by Prof. Hans Clevers, professor of
molecular genetics at the Hubrecht
Institute/UMC Utrecht and president
of the Royal Dutch Academy of Arts
and Sciences, detailed a revolutionary
culturing method that enabled the culturing of mini-guts from single mouse
intestine stem cells. The organoids are
functional miniature organs that can
be grown in tissue culture.
That same group of researchers
has now announced the development
of a culturing system for liver stem
cells and stem cells from pancreatic
cancer. Both sets of research appeared
recently in Cell.
The culturing system for liver
INDIANA CONTINUED ON PAGE 14
HUBRECHT CONTINUED ON PAGE 15
CREDIT: DANIELLE SWANEY
Plasticell awarded
£1.3M from Innovate UK
Induced pluripotent stem cells from the
Krogan lab are pictured here. One goal of the
CCMI is to make cancer-related mutations in
iPS cells and see how the protein interaction
networks change as the cells differentiate.
CREDIT: INDIANA UNIVERSITY
BRIEFS
Indiana University researchers will use $3.3 million from the National Institutes of Health to
embark on a four-year effort to develop improved tools for studying the formation and structure
of cell walls in bacteria and combat antibiotic resistance.
New ammo in the
arms race against
antibiotic resistance
NIH provides grant to Indiana University to build
knowledge base about key bacterial cell processes
BY JIM CIRIGLIANO
BLOOMINGTON, Ind.—A team of chemists
and microbiologists at Indiana University
(IU) announced earlier this year that it will
receive a $3.3-million grant from the National
RESEARCH & DEVELOPMENT
For more information, visit www.DDN-News.com
CCMI
CONTINUED FROM PAGE 12
“We’re going to draw the complete wiring diagram of a cancer
cell,” Krogan explains. “We’re
going to use network biology to
make sense of genomic data, make
physical maps of proteins and
genes and introduce mutations to
see how functions are perturbed.”
While progress in genome
sequencing enables researchers to
decipher hundreds of mutations
found in a patient’s tumor, scientists rarely understand how these
mutations cause cancer or indicate treatment plans. Mutations
in each patient are usually different, but they can lead to the same
type of cancer. Inasmuch as these
mutations are unique to individuals, they attack the same cancer
pathways or genetic circuits. The
complete wiring diagram of the
cell will establish all of the connections between normal and mutated
genes and proteins.
“We have the genomic information already. The bottleneck
is how to interpret the cancer
genomes,” says Ideker. A comprehensive map of cancer cells would
help—and accelerate the development of personalized therapy, the
central aim of what has come to
be called precision medicine. This
process, according to Ideker, “will
enable applications to start with
the genome, identify the genes,
determine their interactions and
use the information for personalized treatment.”
Krogan adds, “The key to understanding genomic information is
being able to place it into biological context. Mutations in tumor
DNA that at first appear to be unrelated may in fact be clustered in
specific pathways or multiprotein
machines in the cell. The information, in context, will point to areas
that we can target with specific
therapies.”
The CCMI is a multimillion-dollar collaboration between the UC
San Diego Moores Cancer Center
and the UCSF Helen Diller Family Comprehensive Cancer Center,
funded by QB3 at UCSF, UC San
Diego Health Sciences and support
from Fred Luddy, founder of ServiceNow, a provider of enterprise
service management software.
Thermo Fisher Scientific is providing mass spectrometers to characterize protein-protein interactions.
The project combines UCSD’s
expertise in extracting knowledge
from big biomedical data sets with
advances developed at UCSF for
experimentally interrogating the
structure and function of cells.
Both schools have two comprehensive cancer centers with samples
that constitute a library of mutations associated with the disease.
Actual patients with cancer and
the stories contained within their
DNA will drive the project, according to the researchers.
UCSD’s primary mission will be
to provide tools for network generation and integrate them into
the project to visualize the effects
of mutations on cells. UCSF will
contribute its ability to generate pluripotent stem cells and its
expertise in genetic engineering.
Additionally, the CCMI will
provide key infrastructure for
the recently announced alliance
between UC San Diego Health Sciences and San Diego-based Human
Longevity Inc., which plans to generate thousands of tumor genomes
from UC San Diego cancer patients.
It will also leverage resources and
information from the National
Cancer Institute (NCI), including
large databases of cancer genomes
and pathways that are being developed in collaboration with the San
Diego Supercomputer Center and
UC Santa Cruz.
David Haussler, director of QB3
at UC Santa Cruz and creator of
the NCI Cancer Genomics Browser, said, “This is an exciting opportunity to utilize the unique NCI
MARCH 2015 | | DDNEWS 13
repository of 1.5 petabytes of cancer genomics data, combined with
proteomic and functional data, to
dive deeper into the molecular processes of cancer.”
For the near term, CCMI will
compare healthy cells to tumor
cells to see how treatments work
on various mutations. Researchers will simplify the procedure
to find three or four pathways to
tailor a particular treatment, not
treat patients with a drug that has
an effect on everything. Initially,
CCMI will focus on breast and
HPV cancer, including head and
neck and cervical cancers, and
then address subcategories. Eventually, the researchers hope to use
genomics to look at other diseases.
“Eventually, patients will be
able to go to their doctors and get
genome sequences that will interpret the diagnosis of diseases and
suggest a path to the cure,” Krogan
concluded. “The specific goal is
personalized medicine.” n
EDITCONNECT: E031508
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RESEARCH & DEVELOPMENT
14 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
BY LORI LESKO
SOMERSET, N.J.—Catal-
president of Advanced
Delivery Technologies, stated in a news
release. “Through invivo toxicology studies,
we have demonstrated
that ADCs generated
using Catalent’s SMARTag platform
have a better toxicity profile than a
conventional ADC, while efficacy
studies also point to an improved
therapeutic index. We look forward
to partnering with Sanofi to support the development of their next
generation of ADC products.”
“Catalent has been in discussions
with a number of potential partners
on the SMARTag platform, and
partner interest has continued to
grow based on continued strong
data,” Michael Riley, vice president
and general manager of Catalent
Biologics, tells DDNews. “Sanofi
will now have the ability to leverage
SMARTag to optimize their ADCs
in development.”
“Our goal with the SMARTag
technology is to partner with leading ADC developers to help them
commercialize their next generation
of products,” Riley continues. “This
agreement provides the opportunity
to leverage our technology with a
leader in the industry, with the ultimate goal of helping Sanofi to get
TOOLS &
TECHNOLOGY
ent Pharma Solutions
and Paris-based pharma giant Sanofi have
launched a joint venture to develop Sanofi’s
proprietary antibodies using Catalent’s SMARTag antibody drug conjugate (ADC) platform. Catalent’s
precision protein-chemical engineering technology will enable
Sanofi to evaluate site-selective
payload conjugation to enhance
ADC pharmacokinetics, efficacy
and safety. The financial terms
were not disclosed.
Sanofi teams will be carrying out
the joint research at Catalent’s facility in Emeryville, Calif., formerly
headquarters to Redwood Bioscience Inc., according to Catalent. In
October 2014, Catalent announced
the purchase of the remaining stake
in Redwood Bioscience after invivo and in-vitro proof-of-concept
milestones were achieved and an
improved toxicity profile was demonstrated with SMARTag ADCs
compared with conventional ADCs.
“We are pleased to enter this
agreement with Sanofi as we jointly work toward the goal of creating better drugs to meet patient
needs,” Barry Littlejohns, Catalent’s
INDIANA
CONTINUED FROM PAGE 12
rch with the potential to uncover a
multitude of targets for new compounds to combat strains of bacteria
that have become resistant to existing antibiotics.
IU’s Clyde Culbertson Professor
of Biology Dr. Yves Brun and associate professor of chemistry Dr.
Michael VanNieuwenhze, two of
the co-authors of the grant proposal, also led an IU team in 2012 that
discovered a nanoscale, fluorescent
chemical probe that pinpoints where
bacterial cells build a compound
called peptidoglycan (PG), which is
a mesh-like polymer that gives shape
and structure to cell walls.
The grant will allow principal
investigators Brun, VanNieuwenhze and IU professor of biology Dr.
Malcolm Winkler to undertake a
four-year project to improve upon
previously discovered methods of
investigating the peptidoglycan
building process.
Co-investigators for the research
will be associate professor of biology
Daniel Kearns, chemistry professor
Stephen Jacobson and associate
professor of biology Sidney Shaw.
The grant will also allow the team
to hire eight to 10 additional
research personnel and purchase
the necessary reagents and lab
supplies for the proposed research.
The research will consist of
three main facets: creating a
second-generation probe that will
improve upon the probe discovered
in 2012, testing two long-standing
hypotheses about PG synthesis
in ovoid bacteria (Streptococcus
pneumoniae), and systematically
screening for genes responsible
for key functions of PG dynamics
and coordination in model species
Escherichia coli and Bacillus subtilis.
The improved probes will be
designed to observe PG synthesis
in action, capturing imaging of PG
construction in E. coli and B. subtilis in greater resolution than previously possible, and in real time. The
probes are called FDAAs for the fluorescent D-amino acids that are used.
“We will synthesize probes with
a variety of properties (e.g. sizes,
colors) with the emphasis on
improved brightness and photostability,” says Brun. “These improved
properties will enhance the utility of these probes in microscopy
applications to analyze the dynamics of PG synthesis.”
Using the newly optimized
probes in concert with the existing ones, the team will analyze
the mechanisms of PG dynamics
in bacterial model systems for two
better ADCs to market.”
The SMARTag platform “provides precise payload positioning
and defined stoichiometry of payload-protein ratios,” he adds. “The
control afforded by the technology
enables identification of superior
drugs from libraries of differentially
designed conjugates. While many
in the industry have recognized the
benefits of ‘site-specific’ technologies to create homogeneous ADCs,
a key differentiator of the SMARTag system vs. most other available
ADC technologies is the ability to
specifically select the site [or sites]
of conjugation on the antibody.”
“Our studies have shown that
varying this site of payload conjugation can have measurable impact
on ADC performance,” he explains.
“By offering partners the ability to
test multiple conjugation sites on a
given antibody, the SMARTag system allows for ADC optimization
that is analogous to a structureactivity relationship study traditionally used in small-molecule
development.”
According to Amy Ba of Sanofi’s global R&D communications,
“Sanofi has been evaluating the
site-specific conjugation field,
and the SMARTag platform is
one of several that we have been
evaluating.”
“Sanofi has a strong commitment
to the field of oncology and evaluADC CONTINUED ON PAGE 16
Sanofi maintains that it has a strong commitment to the field of oncology
and that it sees antibody-drug conjugates as a potential solution to
improve the lives of cancer patients.
MICHAEL BOERSMA—INDIANA UNIVERSITY
Catalent’s tech will help Sanofi evaluate
site-selective payload conjugation to
enhance ADC PK, efficacy and safety
CREDIT: SANOFI
Catalent, Sanofi collaborate on SMARTag, ADCs
Regions of active cell wall synthesis shown by high-resolution imaging of
the bacterial pathogen Streptococcus pneumoniae. Long-term labeling is
revealed with blue FDAA and short-time labeling with red FDAA.
different cell shapes and two cell
envelope architectures.
“We will test two major longstanding hypotheses about the
spatiotemporal coordination of the
elongation and the division PG synthesis machineries and about the
coordination between PG hydrolysis and synthesis in the major model
for ovoid-shaped cells, the pathogen
S. pneumonia,” says Brun. “We will
also analyze PG spatiotemporal
dynamics at super-resolution for
the major model species for rodshaped gram-negative bacteria with
a thin layer of PG (E. coli) and for
rod-shaped gram-positive bacteria
with a thick layer of PG (B. subtilis).”
Finally, the team will take advantage of high-throughput screening
technology and extensive genetic
data relating to these model bacteria species to randomly and systematically screen for genes that may
be involved in PG dynamics and
coordination in bacterial cell walls.
“We will further take advantage of our recent development
of a high-throughput microscopy
screening platform, the availability
of a comprehensive strain collection in which each gene has been
separately deleted and the powerful
genetics of both species,” says Brun.
The goal of this multifaceted
approach is to identify the core principles of PG dynamics and how they
can be modified to yield different
outcomes in dynamics, cell shape,
and cell envelope architecture.
Understanding PG synthesis can
lead to new treatments and targets
for new antibiotics active across
diverse bacterial groups, including
antibiotic-resistant strains.
“At the end of the funding period,
we expect that we will have generated a powerful and unprecedented
pipeline for the high-throughput
isolation of loss-of-function mutants
and conditional alleles defective in
PG synthesis, and for the single-cell
quantitative analysis of their effect
on PG spatiotemporal dynamics,”
says Brun. “Not only will we gain
insight onto the molecular mechanism of PG synthesis and dynamics
in well-established model organisms, but the pipeline can be applied
to any bacterial species, including
pathogens, limited only by the ability to be grown in the laboratory.”
Widely considered an emerging
and urgent health threat worldwide, antibiotic-resistant bacteria
affect more than 2 million Americans each year. n
EDITCONNECT: E031509
For more information, visit www.DDN-News.com
HUBRECHT
CONTINUED FROM PAGE 12
stem cells is detailed in the paper
“Long-Term Culture of GenomeStable Bipotent Stem Cells from
Adult Human Liver,” specifically
the conditions that allow “longterm expansion of adult bile ductderived bipotent progenitor cells
from human liver.” The paper notes
that the expanded cells are highly
stable at both the chromosome and
structural levels, and the cells “can
readily be converted into functional hepatocytes in vitro and, upon
transplantation, in vivo.” The resulting organoids grown from cells
from patients with α1-antitrypsin
deficiency and Alagille syndrome—
an inherited disorder that can lead
to liver disease and/or cirrhosis and
a genetic disorder characterized by
liver damage due to abnormalities
in the bile ducts, respectively—
accurately represent the in-vivo
pathology of the disorders.
This approach, which enables
long-term replication of harvested liver tissue, makes it
possible to culture the equivalent
of a full-grown liver from a single
liver cell over the course of four
months, and the cultured tissue
is genetically similar to healthy
liver tissue and very stable.
Human “mini-livers” cultured
in the lab have been successfully
transplanted into mouse models
with liver damage.
The second paper, “Organoid
Models of Human and Mouse Ductal Pancreatic Cancer,” details the
team’s development of a technology
enabling long-term laboratory
culturing of healthy and diseased
pancreatic stem cells. The work
was co-led by Clevers and Dr. David
Tuveson, professor at Cold Spring
Harbor Laboratory (CSHL) and
director of research for The Lustgarten Foundation.
Culturing either healthy or cancerous pancreatic cells in the lab
has failed in the past, in part due to
the fact that the normal ductal cells
that can become cancerous represent about 10 percent of the cells
in the pancreas. The organoids generated from this culturing method
consist entirely of ductal cells,
excluding the other cell types that
can contaminate pancreas samples.
The organoids are grown as hollow
spheres in a gel-like substance full
of growth-inducing factors and
connecting fibers, and once grown,
they can be transplanted back into
mice, where they accurately duplicate pancreatic cancer.
As noted in the paper, these
organoids “can be rapidly generated from resected tumors and biopsies, survive cryopreservation and
exhibit ductal- and disease-stagespecific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum
of tumor development by forming
early-grade neoplasms that progress to locally invasive and metastatic carcinomas.”
RESEARCH & DEVELOPMENT
“We can now rapidly generate
organoids from any patient, which
offers us the potential to study the
disease in a much wider population.”
Dr. Dannielle Engle of
Cold Spring Harbor Laboratory
“We now have a model for each
stage in the progression of the disease,” said Dr. Chang-Il Hwang, one of
the lead authors of the second paper
working in The Lustgarten Foundation’s Pancreatic Cancer Research
Lab at CSHL directed by Tuveson.
Dr. Dannielle Engle of CSHL,
another lead author of the
“Organoid Models” paper, added
that while biopsies are the current
standard for cancer diagnosis, “We
can now rapidly generate organoids
from any patient, which offers us
the potential to study the disease in
a much wider population.”
The researchers found that
thanks to this method, the tumor
tissue samples from individual
patients can be tested to determine
MARCH 2015 | | DDNEWS 15
their sensitivity or resistance to different cancer drugs.
The technology was also used
to create a ‘Living Biobank’ of cultured pancreatic tumors from a
large group of patients with pancreatic tumors, which was established
with support from the Dutch Cancer Society/Stand up to Cancer. The
biobank is open to cancer researchers and companies worldwide to
aid in the development of new
drugs and therapies for cancer. n
EDITCONNECT: E031510
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RESEARCH & DEVELOPMENT
16 DDNEWS | | MARCH 2015
Agilent tool enhances
integrity of genomics
experiments
SANTA CLARA, Calif.—This winter saw the
announcement by Agilent Technologies Inc.
that it would aid those conducting genomics
experiments to
“enhance integrity”
by helping ensure
quality of tissue
samples. That aid
comes by way of
the addition of a
new feature to Agilent’s Genomic DNA
ScreenTape assay—the DNA Integrity
Number (DIN).
The feature is designed to ensure the
quality of genomics experiments generally,
but especially next-generation sequencing
(NGS). It reportedly builds on Agilent’s
technology for assessing the integrity of
RNA—the RNA Integrity Number, which
Agilent describes as having “become a
market-leading standard.”
With the new software feature, the Agil-
A new feature of Agilent’s Genomic DNA
ScreenTape assay—the DNA Integrity
Number—is designed to ensure the integrity
of genomic DNA.
CREDIT: AGILENT TECHNOLOGIES
According to Agilent, the ability to accurately
assess the quality of DNA samples is
becoming more important as researchers
engage in ever-larger NGS studies.
Kite Pharma announces expanded
agreement with Tel Aviv Sourasky
Medical Center on chimeric
antigen receptor approaches for
cancer immunotherapy
CREDIT: AGILENT TECHNOLOGIES
TOOLS &
TECHNOLOGY
ent Genomic DNA ScreenTape assay is now
said to provide an objective measure of DNA
integrity for a wide range of samples. This
includes not just intact samples from fresh
tissue, but even the highly degraded samples
often obtained from formalin-fixed, paraffinembedded tissues. Agilent expects the DIN
to play a key role in determining the quality
of samples as they enter the NGS workflow,
allowing researchers to better define their
genomic DNA samples, standardize their
integrity assessment and potentially streamline their sequencing workflow.
Agilent notes that the ability to accurately assess the quality of DNA samples is
becoming more important as researchers
engage in ever-larger NGS studies. The
company also theorizes that DIN could
prove invaluable at biobanks, as a tool for
measuring archival quality.
Agilent is making DIN freely available as
a software upgrade. n
SANTA MONICA, Calif.— Kite Pharma
Inc., a clinical-stage biopharmaceutical
company focused on developing engineered autologous T cell therapy (eACT)
products for the treatment of cancer,
today announced that the company has
expanded its agreement with Tel Aviv Sourasky Medical Center in Israel to research
and develop novel approaches to chimeric
antigen receptor (CAR) T cell therapy, the
technology underlying Kite’s most advanced
programs in cancer immunotherapy. Under
the agreement, Kite will collaborate with Dr.
Zelig Eshhar, a leading pioneer in CAR T cell
research and chair of immunology research
within the Tel Aviv SouraskyMedical Center’s Division of Research and Development.
“Zelig’s award-winning research has been
at the center of CAR T cell programs currently advancing in clinical studies. We are
pleased to have an expanded agreement
with Zelig and the Tel Aviv Sourasky Medical Center. We believe this collaboration
will facilitate continued development and
advancement of novel, efficacious and more
selective CAR T cell products for various
tumor types,” said Dr. Arie Belldegrun, Kite
Pharma’s president and CEO.
Eshhar himself stated, “I have dedicated
my career to the advancement of this transformative area of medicine, and I am excited
about the opportunities before us.”
“Originally,” Eshhar continued, “my research had addressed the question of whether
T cells can be programmed to effectively
recognize and eliminate cancerous cells
and to solve the central problem of how and
ADC
CONTINUED FROM PAGE 14
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Call Us
for a
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ates antibody-drug conjugates as a potential solution to improve the lives of cancer
patients,” Ba tells DDNews. “Sanofi has the
great opportunity to launch six new medicines in 2015, with one new launch every
six months for a total of 18 new medicines
by 2020. As part of our research program,
Sanofi has a strong commitment to oncology. Our goal is to invest more in projects
and emerging fields.”
Catalent’s proprietary SMARTag
site-specific protein modification and
cytotoxin-linker technologies developed
by Redwood enable the generation of
homogenous bioconjugates engineered
why cancer cells escape the immune system.
Now, we believe that we can further enhance
this platform technology to develop a whole
new generation of CAR T cell products for
many tumor types. I look forward to the
progress of this program.”
Eshhar recently was named one of the
recipients of the prestigious Massry Prize,
along with Kite collaborator Dr. Steven
Rosenberg, chief of Surgery Branch at
the U.S. National Cancer Institute (NCI),
“We believe this
collaboration will
facilitate continued
development and
advancement of novel,
efficacious and more
selective CAR T cell
products for various
tumor types.”
Dr. Arie Belldegrun, president
and CEO of Kite Pharma
not only for his pioneering efforts in
immunotherapy, but also for his adoptive T
cell approaches to cancer treatment.
In partnership with the NCI Surgery
Branch through a Cooperative Research and
Development Agreement, Kite is advancing
a pipeline of proprietary eACT peripheral
blood product candidates, both CAR and
TCR (T cell receptor) products, directed to
a wide range of cancer indications. n
to enhance potency, safety and stability.
The technology employs natural posttranslational modifications found in
human cells to create one or more aldehyde tags at designated sites on protein
molecules, the company states. These
chemical handles are then stably conjugated to cytotoxic payloads to prevent
their systemic release.
The SMARTag platform provides precise payload positioning and defined
stoichiometry of payload–protein ratios.
The control afforded by the technology
enables identification of superior drugs
from libraries of differentially designed
conjugates, according to the company. n
EDITCONNECT: E031511
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Representatives of Catalent bringing in the close of the New York Stock Exchange on
Sept. 8, 2014. Catalent and Sanofi recently launched a joint venture to develop Sanofi’s
proprietary antibodies using Catalent’s SMARTag antibody-drug conjugate platform.
For more information, visit www.DDN-News.com
MARCH 2015 | | DDNEWS 17
PRECLINICAL
BRIEFS
Covance announces new drug
development offering
PRINCETON, N.J.— Covance Inc. has launched
Early Phase Development Solutions, a multidiscipline approach to early drug development that
will provide sponsors with access to a molecule
solution team of experts from nonclinical, clinical and regulatory disciplines with experience in
early drug discovery and development. The ongoing support from a single point of contact makes
the process more efficient, allowing Covance to
ensure accelerated program timelines can be met.
“Our market research showed that the two
greatest challenges our biopharma clients face
today are continuity of a drug development program—both scientific and operational—and the
need for stronger outsourcing partnerships,” said
Dr. Steve Street, vice president and global general
manager, Covance Early Development. “We created Early Phase Development Solutions to help our
clients overcome those challenges—something
that Covance is uniquely positioned to do given the
depth and breadth of our services and expertise
from the CRO industry as well as global pharma.”
FluCide candidate boasts
promising safety profile
BOVINE EPIPHANY
Cows inspire TSRI researchers to create therapy that fuses hormones and antibodies
BY ZACK ANCHORS
LA JOLLA, Calif.—Scientists at
The Scripps Research Institute (TSRI) have made progress
toward a new therapy that
could be used to treat a range of
conditions involving hormone
deficiencies—and they have
cows to thank for it.
A new study from TSRI suggests that the therapeutic approach
has the potential to significantly
improve quality of life for people
who currently take daily injections of human growth hormone
to treat their conditions. TSRI
research associate Tao Liu, a coauthor of the study, tells DDNews
that researchers were inspired
by the bovine immune system
to develop a compound that
fuses hormones with antibodies.
“We’ve previously found that
immune molecules in cows have
a structure that is quite different
from humans,” says Liu. “We
were inspired by this unique structure to assemble an antibody
with the potential to treat a range
of conditions in humans.”
Current treatments for
conditions that feature hormone
deficiencies often involve injections of human growth hormone
(HGH). While this course of
treatment can be highly effective, it is usually necessary for
patients to receive injections
with great frequency due to the
quickness with which the body
breaks down HGH. In some
cases, the body degrades HGH
within 30 minutes.
“A major disadvantage of
hormones as a treatment is the
need for frequent injections,”
says Liu. “Children with growth
hormone deficiency, for example, have to receive injections of
growth hormone every day, and
Researchers at The Scripps Research Institute took their lead from the
immune systems of cows when they set out to fuse hormones with
antibodies for therapeutic purposes in humans.
that can be very painful for a
little kid.”
TSRI’s study suggests it may
be possible to develop hormonebased treatments that remain
active in the human body long
enough to be administered much
less frequently—perhaps weekly
or monthly. This could be accomplished by fusing hormones
with antibodies, which can
survive for weeks in the body.
An older TSRI study from
COWS CONTINUED ON PAGE 19
WEST HAVEN, Conn.—NanoViricides Inc. has report-
ed that an optimized FluCide drug candidate has
demonstrated a good safety profile in a toxicology
study in rats. The candidate was administered
intravenously at doses of up to 300 mg/kg per
day for 14 days, and no direct adverse clinical
effects were seen upon administration or in gross
organ-level histological examination. This study
was conducted at BASi in a cGLP-like fashion.
The next phase of toxicology package studies will
involve larger animals and will be performed in
a cGLP-compliant manner to provide the safety
and toxicology data required for an Investigational
New Drug submission to regulatory authorities.
IN THIS SECTION
INdiscovery
THISand
SECTION
Drug
development
services
Head
Covance announces new drug
Text�����������������������������������������������������������
development offering.............................. 170
Text............................................................ 0
Hormone therapies
Head
Bovine epiphany...................................... 17
Text����������������������������������������������������������� 0
Influenza
Text............................................................
0
FluCide candidate boasts
promising safety profile........................... 17
Neurology/Gene therapy
Industry-academia attack
on GM1-gangliosidosis........................... 18
Oncology
An answer for glioblastoma?.................. 17
MMRF and Inflection collaborate on new
cancer treatment (MMRF from cover)...... 21
The guiding light...................................... 17
The guiding light
Oregon State’s ‘glowing’
nanotechnology guides cancer surgery,
zaps remaining malignant cells
BY LORI LESKO
Corp., a specialty biopharmaceutical company focused on
developing therapeutic products
to treat ophthalmologic, oncologic and dermatologic diseases,
thinks it may have an answer.
CORVALLIS, Ore.—Targeted toward improving the outcome of
cancer surgery, researchers at Oregon State University (OSU)
have developed and launched a new tumor-seeking weapon
to theoretically extinguish all malignant cancer cells by selectively inserting compounds into the cancer cells, thus allowing
surgeons to identify malignant tissues. Then, in combination
with phototherapy, the tumor will not only be removed, but the
innovative method will kill any remaining cancer cells, both
through mild heating and generating reactive oxygen species.
This procedure may one day answer, at least for some, the
age-old lingering question: Doc, did you get it all?
“It’s about as simple as, ‘If it glows, cut it out,’ David Stauth,
science writer at OSU, stated in a recent news release. “And if
a few malignant cells remain, they’ll soon die.”
The findings, published in the journal Nanoscale, have
shown remarkable success in laboratory animals, Stauth said.
The concept should allow more accurate surgical removal of
solid tumors at the same time as it eradicates any remaining
cancer cells. In laboratory tests, it completely prevented cancer
recurrence in mice after phototherapy.
“This is kind of a double attack that could significantly improve
the success of cancer surgeries,” says Oleh Taratula, an assistant
professor in OSU’s College of Pharmacy. “With this approach,
cancerous cells and tumors will literally glow and fluoresce
RES-529 CONTINUED ON PAGE 18
GLOW CONTINUED ON PAGE 20
Pictured above: Dr. David Sherris (currently chief scientific officer of
RestorGenex) when he was president of Paloma Pharmaceuticals Inc.,
talking at the 16th Mars Society Convention about an agent that
showed both anticancer properties and radiologic protective benefits.
An answer for
glioblastoma?
RES-529 targets TORC1 and TORC2
protein complexes in dissociative manner
BY ILENE SCHNEIDER
BUFFALO GROVE, Ill.—Gliobla-
stoma, also known as glioblastoma multiforme (GBM), is
the most common and most
aggressive type of primary brain
tumor in adults. RestorGenex
18 DDNEWS | | MARCH 2015
PRECLINICAL
For more information, visit www.DDN-News.com
Trio of Lysogene, UMass
Medical School and Auburn
University announce
collaboration in CNS disease
BY LLOYD DUNLAP
PARIS—Lysogene, a clinical-stage gene ther-
apy biotechnology company in France, has
entered into a strategic collaboration with
the University of Massachusetts Medical
School (UMMS) in Worcester and Auburn
University (AU) in Alabama. Through the
collaboration, the three organizations will
develop IND-supporting preclinical studies
in GM1-gangliosidosis, a rare inherited disorder characterized by severe neurological
impairment, using adeno-associated virus
(AAV) gene therapy technology.
The collaboration will combine Lysogene’s
translational and clinical expertise in gene
therapy for central nervous system (CNS) disorders with the unique preclinical expertise
and infrastructure of UMMS and AU to design
and test innovative AAV-based gene therapy
RES-529
CONTINUED FROM PAGE 17
RestorGenex presented scientific data on
a potential treatment for GBM at the Keystone Symposia Series on PI 3-Kinase (PI3K)
Signaling Pathways in Vancouver, British
Columbia, in January.
“GBM is a disease with a very poor prognosis,” said Stephen M. Simes, CEO of
RestorGenex. GBM is challenging to treat
because the cells within the tumor are very
resistant to most treatments. In addition,
these rapidly growing tumors tend to have
a tentacle-like structure, so it can be difficult to fully remove the tumor surgically.
Titled “Validation of RES-529, a novel
TORC1/TORC2 allosteric dissociative PI3K
inhibitor in glioblastoma multiforme,” the
RestorGenex presentation showed how the
approaches to treat GM1-gangliosidosis.
The development of a potential treatment
for GM1-gangliosidosis using AAV gene therapy was initiated in 2005 by Dr. Miguel SenaEsteves, associate professor in the neurology
department and the Gene Therapy Center at
UMMS, and Dr. Douglas R. Martin, associate professor in the Scott-Ritchey Research
Center and department of anatomy, physiology and pharmacology at AU. The approach
developed by the investigators uses AAV vectors to treat the entire brain and spinal cord
after injection at only a few intracranial sites.
Lysogene and the two U.S academic institutions forged their collaboration on their
shared interest for AAV-based gene therapies in CNS disorders, Karen Aiach, founding
president and CEO of Lysogene, tells DDNews.
“More specifically,” she adds, “in lysosomal storage disorders (LSDs). Based on in-depth due
diligence performed by the company to identify
a new, robust and commercially viable target for
its pipeline, the two U.S. institutions attracted
TRIO CONTINUED ON PAGE 20
proprietary first-in-class PI3K/Akt/mTOR
pathway inhibitor is capable of dissociating
both TORC1 and TORC2.
“This, and other work, supports the rationale for RestorGenex’s plans to advance
RES-529 into clinical trials in GBM,” said
Dr. David Sherris, chief scientific officer of
RestorGenex. Sherris explained that RES529 is an “allosteric, dissociative, first-inclass inhibitor of the PI3K/Akt/mTOR pathway.” It inhibits both TORC1 and TORC2
and is mechanistically differentiated from
other PI3K inhibitors in development.
“Signaling components of the PI3K pathway are central regulators of cell proliferation, growth, differentiation, survival and
angiogenesis,” Sherris added.
The poster presentation discussed invitro and in-vivo data from preclinical stud-
CREDIT: UNIVERSITY OF MASSACHUSETTS
Industry-academia attack on GM1-gangliosidosis
The University of Massachusetts Medical School, the Aaron Lazare Medical Research Building
of which is pictured here, is engaged in a collaboration with Paris-based Lysogen and fellow
U.S. academic and research institution Auburn University to develop IND-supporting preclinical
studies in GM1-gangliosidosis.
ies evaluating RES-529 in GBM, a disease
often characterized by elevated expression
of PI3K. In the first study, RES-529 demonstrated an ability to inhibit signal transducers of the PI3K pathway controlled by
TORC1 and TORC2 in a variety of tumor
cells, including cells that have lost tumor
suppressor PTEN.
A second study compared RES-529 with
two catalytic inhibitors of the PI3K pathway now in the clinic: a combination PI3K/
mTOR agent and a combination PI3K/Akt
agent. RES-529 showed a twentyfold to
more than hundredfold increase in activity above other inhibitors and the ability to
inhibit tumor cell survival up to two orders
of magnitude over that of a rapamycin analog PI3K inhibitor in a tumor model known
to show resistance to TORC1 inhibition.
A third study showed RES-529 penetrates
the blood-brain barrier. This was supported
by efficacy data of RES-529 in an orthotopic GBM xenograft model where RES529 showed an improvement in survival
vs. control, similar to radiation treatment.
When combined with radiation, RES-529
showed synergy extending survival above
that of either RES-529 or radiation alone.
Sherris concluded, “The data both as
monotherapy and in combination therapy
with radiation suggest that RES-529 should
be evaluated in glioblastoma where standard of care has at best resulted in approximate survival of 12 months—fewer than 25
percent of patients survive two years, and
fewer than 10 percent of patients survive
five years.” ■
EDITCONNECT: E031513
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2013 showed that compounds providing a potential model for fusing
hormones and antibodies exist in
the immune system of cows. The
2013 study of the bovine antibody
revealed an unusual structure that
features a round base with a long
amino-acid stalk extending outwards. On the top of the stalk is a
“knob region” that was believed to
bind to pathogens.
Researchers designed the new
TSRI study to test whether it
is possible to switch the knob
region of the bovine antibody
with DNA from a human hormone, such as HGH. They first
pursued this theory by using
recombinant DNA technology
to fuse HGH to a coiled version
of the bovine antibody’s stalks.
The results were promising: the
fusion proved stable and did not
prevent HGH from retaining its
normal function.
The next step of the study
involved an attempt to create a fully
humanized version of the antibody
to test whether it was possible for
“We’ve previously
found that
immune molecules
in cows have a
structure that is
quite different
from humans.”
Tao Liu, a TSRI
research associate
the molecules to be applied in
human therapy. Researchers used
the humanized anticancer drug
Herceptin as the antibody base
to develop an antibody-hormone
molecule without any cow DNA.
“We used Herceptin because it has
already been used as a drug to treat
cancer and it has a well-established
profile,” says Liu. “We modified it so
it didn’t have anything to do with
treating cancer and its only function was to help the growth hormone
grow correctly and to improve the
half life of the compound.”
The researchers then tested
their antibody-HGH molecule in
rat models. They found that HGHdeficient rats that received the treatment grew normally. In fact, the
treated rats only needed injections
two times a week to grow, compared
with daily injections for rats given
HGH without the antibody base.
“It acts just like the normal
growth hormone,” according to
Liu. “This means the treatment
might only need to be injected
once a week or even once a month
in humans. It would be so much
easier for patients.” The study
ultimately demonstrated that
human hormones and antibodies
can be fused together in a way that
mimics the long, stalk-like cow
antibodies.
The senior authors of the new
study, which was published in the
journal Proceedings of the National
Academy of Sciences, were Peter
Schultz of TSRI and Feng Wang of
the California Institute for Biomedical Research.
The researchers are continuing
to explore how this new therapeutic approach could provide longerlasting doses of HGH that would
improve treatments for people with
conditions ranging from Turner
Syndrome, which causes short
stature in females, to low birth
weight. Liu believes the therapy
could eventually improve treatments for an even wider spectrum
of individuals, including those
who require insulin to treat type 2
diabetes. Reducing the frequency
of injections for all these conditions, he says, has the potential to
improve patient compliance and
quality of life. ■
EDITCONNECT: E031502
MARCH 2015 | | DDNEWS 19
CREDIT: TSRI
COWS
Copyright © 2015 PerkinElmer, Inc. 400285_09 All rights reserved. PerkinElmer® is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners.
th
PRECLINICAL
For more information, visit www.DDN-News.com
Researchers at The Scripps Research Institute designed a new study recently
to test whether it is possible to switch the “knob region” of a bovine antibody
with DNA from a human hormone, such as human growth hormone.
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20 DDNEWS | | MARCH 2015
PRECLINICAL
TRIO
neurodegenerative disorder characterized
by severe cognitive and motor developmental
Lysogene’s interest because of particularly delays resulting in death of most patients at a
compelling preclinical proof-of-concept data very young age. It is caused by mutations in the
in GM1-gangliosidosis, a model disease for neu- GLB1 gene, which encodes an enzyme called
beta-galactosidase necessary for recycling of
rological disorders with motor impairment.”
Lysogene’s ultimate mission is to transl- a molecule (GM1-ganglioside) in neurons.
ate the initial proof of concept into a viable This brain lipid is indispensable for normal
drug development program to the benefit of function, but its overabundance causes neupatients in urgent need. The parties are colla- rodegeneration, resulting in the severe neuborating on IND-supporting preclinical stu- rological symptoms of GM1-gangliosidosis.
LSDs are attractive candidates for gene
dies. Under the agreements, Lysogene-sponsored efficacy studies will be performed at replacement therapy because they are monoboth UMMS and AU. The company will also genetic conditions, and genetic correction
design and execute translational activities, of a small subset of neural cells may be sufi.e. GMP vector manufacturing, toxicity and ficient to target large regions of the CNS,
biodistribution studies, regulatory affairs, as secreted lysosomal enzymes can diffuse
and be captured by adjacent and distal cells
IND procedure and clinical development.
Preclinical studies demonstrated a remark- (cross-correction mechanism). Moreover,
able extension in lifespan from eight months tight regulation of produced enzyme levels
in untreated GM1 cats to greater than 4.5 years is not required because a low level of enzyme
in AAV-treated cats, with dramatic improve- activity (around 10 percent) may be sufficient
ments in quality of life. Results were published to have therapeutic effects and conversely
supraphysiological levels of many of the
in Science Translational Medicine in 2014.
“We are thrilled by our collaboration with acidic hydrolases have no deleterious effect.
In the past decade, recombinant adenoUMMS and AU, which constitutes a significant step towards the development of a treat- associated virus (rAAV) approaches have
ment for patients affected with GM1-ganglio- rapidly advanced to the forefront of gene
sidosis. For each of these patients and their therapy, with hundreds of subjects injectfamilies, there is currently no option and an ed and with no serious adverse events yet
urgent need for a safe and effective therapy,” reported. According to Lysogene, rAAV vecaccording to Aiach. “AAV-based therapies are tors are excellent tools in gene therapy for
particularly suitable for inherited disorders treatment of neurological diseases as they
of the CNS. In this new program, Lysogene transduce post-mitotic cells that mediate
will leverage its unique capacity to develop the sustained, long-term gene expression
these therapies and bring them to patients that is required to treat chronic diseases.
with unmet needs. We will also reinforce our Injected in the CNS, AAVs can be transscientific and technology base through our ported along neuronal connections to
distal sites and secreted enzymes can be
collaboration with leaders in the field.”
“Collaborating with Lysogene will allow transported antero and retrograde to crossus to leverage their clinical and translational correct cells distal from the injection site.
Other AAV serotypes with different
expertise and advance the development of
a gene transfer therapy for treating patients expression cassette constructs will be tested
affected with GM1-gangliosidosis,” said Sena- in GM1 murine and feline models, as well
Esteves. “In our minds, what ultimately mat- as new injections routes to determine the
approach to be translated to human
ters
is the ability to deliver a treatment
to the4:58optimal
Indigo Bio Ad March 2015.pdf
1
2/17/15
PM
children suffering from this horrible disease.” patients. ■
GM1-gangliosidosis is a rare, inherited EDITCONNECT: E031515
For more information, visit www.DDN-News.com
GLOW
CONTINUED FROM PAGE 18
CONTINUED FROM PAGE 17
when exposed to near-infrared light, giving
the surgeon a precise guide about what to
remove. That same light will activate compounds in the cancer cells that will kill any
malignant cells that remain. It’s an exciting
new approach to help surgery succeed.”
This research was done with ovarian
cancer cells. Ovarian cancer is the deadliest of all cancers affecting the female
reproductive system, with very few effective treatments available, according to the
National Institutes of Health (NIH).
The work is based on the use of a known
compound called naphthalocyanine,
which, when exposed to near-infrared
light, can make a cell glow to guide the
surgeon, OSU researchers stated.
However, naphthalocyanine isn’t watersoluble, and also tends to clump up, or
aggregate, inside the body during the process, thus losing its ability to make cells glow
and generate reactive oxygen species. This
also makes it difficult or impossible for it to
find its way through the circulatory system
and take up residence only in cancer cells.
OSU experts overcame these problems
by use of a special water-soluble polymer,
called a dendrimer, which allows the napthalocyanine to hide within a molecule
that will attach specifically to cancer cells,
Stauth said. The dendrimer, an extremely
tiny nanoparticle, takes advantage of certain physical characteristics that blood
vessels leading to cancer cells have, but
healthy ones do not. It will slip easily into a
tumor, but largely spare any healthy tissue.
This “one-two punch of surgery and a
nontoxic, combinatorial phototherapy
holds significant promise,” Taratula says.
“It’s quite different from existing chemotherapies and radiotherapies.” He adds that
this process “could someday eliminate—
or at least reduce—the need for chemotherapy and radiation. For many cancers,
surgery is a first choice of treatment. In
coming years, we may have a tool to make
that surgery more precise, effective and
thorough than it’s been before.”
“Our findings highlight substantial
progress in employing a single-agent-based
nanomedicine platform capable of both
NIR fluorescence imaging and anticancer
therapy (combinatorial phototherapy in
this case) with the near future prospective
to detect and eradicate unresected cancer
cells intraoperatively,” Taratula continues.
“What we have learned from these studies
is that it is possible to visualize and destroy
cancer cells with a single agent, minimizing the cost, time and toxicity of intraoperative anticancer therapy.”
In order to get FDA approval for clinical trials with humans, the convincing
therapeutical and safety results in animals
have to be obtained, Taratula notes. “At the
moment, we are continuing complete evaluation of this modality in mice. However,
we are getting ready to test this system
on dogs in collaboration with the Oregon
State College of Veterinary Medicine.”
Systems with technology similar to this
are also being tested by other researchers,
but some of them require several imaging
and therapeutic agents, repeated irradiation and two lasers, OSU researchers stated.
This increases cost and may lessen effectiveness and increase the risk of side effects.
This nanotechnology work was initially
supported by OSU College of Pharmacy.
“Recently, we received $120,861 from
Venture Funds OSU to optimize the developed nanomedicine platform and complete critical animal studies, including
detailed efficacy and toxicity, to advance
this technology,” Taratula said. “Earlier, in
2013, $40,000 from the Medical Research
Foundation of Oregon also supported initial work for this project.”
With cuts in grant funding, though, the
future is uncertain. ■
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CONTINUED FROM PAGE 1
kinase inhibition is said to selectively inhibit PIM and PI3K without
affecting the activity of other
kinases.
“Initial preclinical data we
have generated for IBL-202 holds
promise for those patients suffering
with multiple myeloma,” according
to Darren Cunningham, CEO of
Inflection Biosciences. “MMRF
support will greatly assist us in
further evaluating the potential
of IBL-202 for patients with multiple myeloma, one of the many
indications we hope to consider.”
The MMRF is working with
Inflection Biosciences through its
Translational Network of Excellence program, which supports critical research at leading academic
medical centers focused on promising investigational therapies for
multiple myeloma.
“Inflection Biosciences, and its
innovative PIM/PI3K program,
is precisely the type of visionary
biotech/pharma partnership the
MMRF is committed to, in our
relentless pursuit of promising
treatment options for multiple
myeloma,” according to Walter M.
Capone, president and CEO of the
MMRF. “The MMRF launched its
Translational Network of Excellence last year to advance the most
promising research for novel targets and drug validation, immune
biology, myeloma-related diseases
and minimal residual disease. We
are tremendously excited to partner with Inflection Biosciences in
the development of this novel and
potentially promising therapy.”
Dr. Michael O’Neill, director
of research and development at
Inflection Biosciences, added,
“This collaboration with a leading
cancer research foundation is a
tremendous validation for our compound and our work so far. We look
forward to working with the MMRF
and its network of researchers to
establish the effectiveness of our
compound in multiple myeloma.”
In other recent MMRF news, but
on the discovery-oriented front in
this case, MMRF announced that
it has partnered with Cambridge,
Mass.-based GNS Healthcare, a
provider of analytics solutions for
driving personalized interventions
that improve population health,
in a collaboration to speed the
discovery of innovative treatments for patients with multiple
myeloma.
The effort is said to “combine
the unprecedented genomic and
clinical data from the MMRF’s
landmark CoMMpass Study with
revolutionary GNS machine learning platforms and rapid computer
simulations. The work supports the
development of computer models
of myeloma disease that may
uncover novel molecular pathways
that can prevent progression of
disease and address the unmet
treatment needs of patients with
multiple myeloma.”
CoMMpass is a longitudinal study of 1,000 newly diagnosed patients with active multiple myeloma. Its objective is
to map each of these patients’
genomic profiles to clinical outcomes to develop a more complete
understanding of patient responses
to treatments.
“Through creative, dynamic
partnerships, we continually build
new research models to accelerate
development of the most promising
treatments for patients with multiple myeloma,” said the MMRF’s
Capone. “This collaboration with
GNS to apply leading-edge computer models and analytics to uncover
disease pathways in the diverse
CoMMpass data set exemplifies
this strategy.”
GNS will use an in-silico process,
applying its MAX architecture
and patented REFS inference
engine and simulation platforms
to the CoMMpass data. REFS will
identify causal drivers and underly-
MARCH 2015 | | DDNEWS 21
ing molecular processes of disease
progression. REFS will also discover
the most likely targets for therapeutics to treat, and perhaps to predict
and prevent, relapses and refractory
disease. REFS will also discover
predictive diagnostic biomarkers
that determine which treatments
will work and for which patients.
“This work embodies the transformative role for Big Data analytics
to uncover specific treatment
protocols that have a much better
chance of success for individual
patients,” says Colin Hill, CEO
and co-founder of GNS. “REFS
turns large datasets into computer
models that reveal new molecular pathways and targets that,
up until now, could not be easily
identified. It ultimately accelerates
many of the traditional steps in the
drug discovery and development
process, bypassing obstacles that
often delay or prevent promising,
new treatments from reaching
patients.” ■
EDITCONNECT: E031512
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22 DDNEWS | | MARCH 2015
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Pennsylvania Convention Center Philadelphia April 18-22, 2015
n
Dr. Kenneth C. Anderson, director of the Jerome Lipper
Multiple Myeloma Center and LeBow Institute for Myeloma
Therapeutics at the Dana-Farber Cancer Institute in Boston
■■ Dr. Carlos L. Arteaga, director of the Center for Cancer Targeted Therapies, director of the Breast Cancer Program and
associate director for clinical research at Vanderbilt-Ingram
Cancer Center of Vanderbilt University in Nashville, Tenn.
■■ Dr. Anton J.M. Berns, senior group leader of the Division of
Molecular Genetics at the Netherlands Cancer Institute in
Amsterdam and director of the Skoltech Center for Stem Cell
Research in Moscow
■■ Dr. Bruce A. Chabner, director of clinical research at Massachusetts General Hospital in Boston
■■ Dr. Ronald A. DePinho, president of the University of Texas
MD Anderson Cancer Center in Houston
■■ Dr. Susan D. Desmond-Hellmann, CEO of the Bill & Melinda
Gates Foundation in Seattle
■■ Dr. Robert N. Eisenman, a member of the Division of Basic
Sciences at Fred Hutchinson Cancer Research Center in
Seattle
■■ Dr. Douglas R. Lowy, deputy director of the Center for Cancer Research, chief of the Laboratory of Cellular Oncology
and head of the Signaling and Oncogenesis Section at the
National Cancer Institute in Bethesda, Md.
■■ Dr. Carol L. Prives, Da Costa Professor at Columbia University
in New York City
■■ Dr. Steven A. Rosenberg, chief of surgery at the National
Cancer Institute
■■ Dr. Craig B. Thompson, president and CEO of Memorial Sloan
Kettering Cancer Center in New York City
■■
Bringing cancer
discoveries to the patients
AACR brings the
world’s largest cancer
research conference
to Philadelphia
T
BY LLOYD DUNLAP
HE AMERICAN ASSOCIATION for Cancer Research
(AACR) Annual Meeting
2015, which AACR President Dr. Carlos Arteaga
reminds us is the largest cancer research conference in the
world, will highlight the “latest, most
exciting” discoveries in every area of cancer research and is designed to provide
a unique opportunity for investigators
from all over the world to meet, interact
and share their insights. This year’s meeting theme, “Bringing Cancer Discoveries to Patients,” underscores the vital and
inextricable link between discovery and
treatment, Arteaga says, and it reinforces
the fact that research underpins all the
progress being made in the field toward
cancer cures.
CREDIT: © 2014 AACR/TODD BUCHANAN
Research will formally induct its 2015 class of elected
fellows of the AACR Academy at the AACR Annual Meeting 2015 to be held in Philadelphia from April 18-22.
The academy serves to recognize and honor distinguished scientists whose major scientific contributions
have propelled significant innovation and progress against
cancer. All fellows are nominated and elected through a
peer-review process conducted by existing fellows of the
AACR Academy and ratified by the AACR Executive Committee. This process involves an assessment of each candidate on the basis of his or her scientific achievements in
cancer research and cancer-related biomedical science.
“Our 2015 class of fellows includes 11 luminaries in the
field of cancer research, in honor of the 11 founders of
the AACR in 1907. We are delighted to recognize the
incredible scientific accomplishments of these illustrious
researchers and celebrate how their dedicated efforts
have helped accelerate the pace of progress against
many of the hundreds of diseases we collectively call
cancer,” said Dr. Margaret Foti, CEO of the AACR.
This brain trust of global leaders in cancer research offers
invaluable insight into the future of cancer research and
patient care and continues to work with the AACR in its
mission to prevent and cure all cancers.
Members of the 2015 class of fellows of the AACR
Academy are:
A view from the AACR Annual Meeting 2014. This year’s event will be held in Philadelphia.
Looking to the present
“This year is very exciting,” states Dr.
Lewis C. Cantley of the Sandra and
Edward Meyer Cancer Center at Weill
CREDIT: © 2014 AACR/TODD BUCHANAN
AACR Academy inducts 11
PHILADELPHIA—The American Association for Cancer
n
Attendees of last year’s meeting are pictured here. This year’s attendees will enjoy a large
roster of speakers, hundreds of invited talks and more than 6,000 proffered papers from
researchers all over the world.
Cornell Medical College, the AACR 2015
program committee chairperson. “A lot
of progress has been made over the past
year, particularly in immune therapy, targeted therapies and molecular medicine.
There will be several major sessions in
these areas and also on clinical trials,
which will be emphasized more than in
previous years. New drugs hitting new
targets will be featured as part of this
year’s emphasis on patients. Novel targets—the P13K gene, for example, that
is often mutated in breast cancer—will
be discussed.”
There will also, he says, be lectures discussing the biochemistry behind trials.
“Notably, the Obama administration
provided additional funding in the area of
precision medicine during the past year,”
Cantley notes, “and we’ll have sessions
focused on molecular therapy in this area.”
In the area of immune therapy, new targets have been discovered in melanoma,
lung and pancreatic cancer.
“Some patients are cured, others don’t
respond at all,” Cantley observes. There
will be a session exploring why this is
AACR 2015 CONTINUED ON PAGE 23
AACR 2015
For more information, visit www.DDN-News.com
AACR 2015
Vanderbilt-Ingram Cancer Center’s associate director for Clinical Research, leader of the Breast
Cancer Research Program, director of the Center for Cancer Targeted Therapies and Donna S. Hall
Chair in Breast Cancer.
A summary of the “Vision for the
Future” session will be provided by
Jose Baselga of the Memorial Sloan
Kettering Cancer Center in New
York City.
Cantley’s focus is targets and preclinical work, Nelson is an expert
CONTINUED FROM PAGE 22
and discussing new targets and
new approaches. “Early-stage
trials will focus on mechanisms
of resistance,” adds Arteaga, who
works at Vanderbilt-Ingram Cancer Center.
Prevention will also be a topic
of considerable attention. A recent
article in Science suggested that up
to one-third of all cancers could be
prevented if smoking, obesity and
diabetes were avoided. How lifestyles figure into prevention will
be discussed.
Arteaga also noted the presumptive links between obesity and
diabetes and their links to cancer
which will be the subject of two
sessions. Insulin resistance, he
observes, may be linked to cancer. “There are signals of hope,” he
states, “and we are the window to
the rest of the world.”
in prevention and epidemiology
and Arteaga’s focus is clinical trials.
“Themes of the session are likely
to include precision medicine and
what it’s telling us, immune combination therapies and exciting clinical trials,” Cantley opines.
For everyone—presenters,
early-career and established
researchers, clinicians and advocates—AACR’s annual meeting
is a must-attend event, according to Cantley, who says, “We are
developing a comprehensive and
APRIL 18-22, 2015
PENNSYLVANIA CONVENTION CENTER
PHILADELPHIA, PA
MARCH 2015 | | DDNEWS 23
multidisciplinary program, with
an outstanding roster of speakers, hundreds of invited talks and
more than 6,000 proffered papers
from researchers all over the
world. We want to thank the Program Committee co-chairpersons
and Education Committee members for their incredible guidance
in shaping an innovative program
that will be both enjoyable and
educational to all attendees and
attract major media attention
from around the world.”
“Together we are making
astounding progress in the fight
against cancer,” Cantley continues.
“It is taking less time than ever for
our research to be translated into
improved prevention, diagnosis and
treatment strategies for patients.
This is an exciting time for cancer
research. By attending the AACR
Annual Meeting, you will find ideas,
people and moments that provide
you with renewed energy, inspiration and focus in your work.” n
EDITCONNECT: E031529
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Vision for the Future
New this year will be a wrap-up
session on the final day of the
conference, chaired by M. Celeste Simon of the Abramson
Family Cancer Research Institute
in Philadelphia. The session will
distill “what’s new and important
down to the hour-and-a-half
session, collect and present the
key information with supporting
slides,” Cantley notes, with a rueful
aside that admits to the enormity
of the task. “I’ll have a lot of help,”
he adds, with colleagues and staff
working throughout the duration
of the conference to aid in the
process.
The presenters will be Cantley,
the Margaret and Herman Sokol
Professor and director of the
Meyer Cancer Center at Weill
Cornell Medical College; Dr.
William G. Nelson, the Marion
I. Knott Director and director
of the Sidney Kimmel Comprehensive Cancer Center at Johns
Hopkins University; and Arteaga,
CST development scientist
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AACR 2015
24 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
Plenary and educational sessions at the annual meeting
Opening Plenary: The
Genome and Beyond
Sunday, April 19, 9 a.m. to 12:15 p.m.
Chairperson: Lewis C. Cantley, Sandra and
Edward Meyer Cancer Center, Weill Cornell
Medical College, New York
■■ “Insights from cancer genomes into the
mutational processes underlying cancer
development” by Michael R. Stratton, Wellcome Trust Sanger Institute, Cambridge, U.K.
■■ “Above the genome: The epigenome and its
biology and translational potential” by Stephen B. Bayline, Johns Hopkins University
School of Medicine, Baltimore, Md.
■■ “Engineering the cancer genome” by Tyler
Jacks, David H. Koch Institute for Integrative
Cancer Research at MIT, Cambridge, Mass.
■■ “Using genomics to personalize cancer immunotherapy” by Robert D. Schreiber, Washington University School of Medicine, St. Louis
Precision Medicine
Comes to Cancer
Prevention and Screening
Monday, April 20, 8:15 a.m. to 10:15 a.m.
This session will include four presentations that highlight recent
advances in cancer prevention.
The first presentation will focus
on the use of multitarget stool DNA
testing to enhance colorectal cancer screening. The second presentation will provide an update of our
understanding of the chemopreventive properties of aspirin. The identification of molecular endpoints
and pathways that help to identify
individuals most likely to benefit
from aspirin will be reviewed.
The third presentation will focus
on liver cancer, which remains
among the top causes of cancer mortality in the world. Evidence will be
presented that liver injury is carcinogenic because it stimulates regenerative responses that relax forces which
normally constrain the inherent multipotency of adult liver cells.
The final presentation will focus
on HPV-related cancers. The latest
advances in reducing the burden
of HPV-related cancers through
primary and secondary prevention
will be reviewed.
Chairperson: Andrew J. Dannenberg.
Weill Medical College of Cornell University,
New York
■■ “Stool DNA detection of colorectal neoplasia: A new high bar for noninvasive screening” by David A. Ahlquist, Mayo Clinic,
Rochester, Minn.
■■ “Molecular risk stratification for aspirin chemoprevention” by Andrew T. Chan, Massachusetts General Hospital, Boston
■■
“Early Detection and Prevention of Liver
Cancer: Leveraging Lessons Learned from
Liver Repair” by Anna Mae E. Diehl, Duke
University School of Medicine, Durham, N.C.
■■ “Drastically reducing HPV-associated cancers through etiologically based primary and
secondary prevention” by Douglas R. Lowy,
Laboratory of Cellular Oncology, Center for
Cancer Research, National Cancer Institute,
Bethesda, Md.
■■
Drug Resistance
Tuesday, April 21, 8:15 a.m. to 10:15 a.m.
Drug resistance is the primary
challenge faced by all practicing
oncologists. The advent of targeted therapies has provided exciting
opportunities not only to understand the mechanisms through
which resistance occurs, but also to
design approaches that overcome
this resistance. The presentations
in this session will describe the
latest developments in this area of
research, from the perspectives of
genetics, drug development, clinical application and cell biology.
Chairperson: Bert Vogelstein, Johns
Hopkins Kimmel Comprehensive Cancer
Center, Baltimore, Md.
■■ “Drug resistance: A genetic perspective” by
Bert Vogelstein
■■ “Genetic screens to understand drug resistance” by Alan Ashworth, UCSF Helen Diller
Family Comprehensive Cancer Center, San
Francisco
■■ “Drug resistance: Translating discoveries
into the clinic” by Alice T. Shaw, Massachusetts General Hospital Cancer Center, Boston
■■ “Drug resistance: A cell biologist’s perspective” by Joan S. Brugge, Harvard Medical
School, Boston
■■
Oncology Meets
Immunology: Not Just
Another “Hallmark”
Wednesday, April 22, 8 a.m. to 10 a.m.
It is now well appreciated that
a fundamental aspect of cancer
biology involves interactions of
neoplastic cells with the immune
system, which can either promote
or inhibit tumor growth, depending on complex networks in the
tumor microenvironment. Mechanistic insights from basic studies in
cancer immunology have resulted
in novel, rational therapeutics for
patients with advanced cancer that
have produced unprecedented
clinical results, even in tumors not
previously regarded as amenable to
such approaches. The consensus in
the field—to be illustrated in this
plenary session—is that we have
only seen the tip of the iceberg for
cancer immunotherapy, posing a
challenge to investigators, advocates, government, industry and
others to capture this opportunity
quickly and fully for the benefit of
our patients.
Chairperson: Robert H. Vonderheide,
Abramson Cancer Center of University of
Pennsylvania, Philadelphia
■■ “Engineering improved cancer vaccines”
by Glenn Dranoff, Dana-Farber Cancer
Institute, Boston
■■
CREDIT: B. KRIST FOR VISIT PHILADELPHIA
B
ECAUSE IT IS NOT possible to attend every
session at AACR’s
annual meeting, a new
plenary session will
provide meeting highlights spanning basic, translational and clinical science, as well as prevention
and early detection. Four plenary
sessions featuring leading experts
in their field have been developed
to cover topics of broad importance
and areas of growth.
Built in 1926, the Benjamin Franklin Bridge, which traverses the Delaware River, connects Philadelphia, the nation’s
fifth-largest city, and New Jersey.
“Leukocytes as targets for therapy in solid
tumors” by Lisa M. Coussens, OHSU Knight
Cancer Institute, Portland, Ore.
■■ “Fatal Attraction: A new story featuring the
immune system and pancreatic cancer” by
Elizabeth M. Jaffee, Johns Hopkins University, Baltimore, Md.
■■ “The mechanistic basis of cancer immunotherapy” by Ira Mellman, Genentech Inc.,
South San Francisco, Calif.
■■
Educational Sessions
In addition to these Plenary Sessions, there are a number of additional Educational Sessions that are
expected to be of major interest to
AACR attendees.
Tumor Immunology and
Immunotherapy for the
Non-Immunologist
Saturday, April 18, 8 a.m. to 10 a.m.
This session is intended to familiarize non-immunologists with
fundamental immune responses
to cancer and highlight innovative
strategies for immunotherapy of
cancer. It will also be informative
to tumor immunologists as they
will learn of the latest research
efforts of the speakers. Immediately following the session, the
Cancer Immunology Working
Group has set up one-on-one
round table tutorials with experts
in the field. This session will be
held from 10 a.m. to noon in the
Liberty Ballroom (Level 3) of the
Philadelphia Marriott Downtown
for participants who are interested
in learning more.
The immune system is a powerful deterrent to cancer development and progression, and its
evasion is a key hallmark of cancer. Innate immunity serves as the
first line of defense which, when
breached, allows the establishment
of a tumor that can create an environment conducive to suppression
of adaptive immunity against cancer. With loss of innate and adaptive immunity, the growth potential
of tumors goes unchecked.
Ironically, inflammation may
positively or negatively impact cancer immunity and tumor growth.
Recent work on inflammation and
cancer points to the gut microbiome as an important component
in balancing immune responses to
cancer. Better understanding of the
underlying mechanisms of immune
modulation in cancer is needed to
develop new therapeutic strategies
that can effectively recover immunity against cancer and result in a
durable clinical outcome and better
patient survival.
The presentations in this session
will touch upon all these areas,
beginning with the microbiota, followed by deliberation on the role
of various types of innate lymphoid
cells and T cells and bringing to the
clinic practical approaches to treat
cancer from lessons learned. What
antigens T cells must recognize to
tame the cancer is also a critical
issue, as well as how neoantigens
created by mutant genes in the cancer cell can be identified and put to
use. There will be a brief discussion
after each presentation.
Chairperson: Julie Y. Djeu, Moffitt Cancer
Center and Research Institute, Tampa, Fla.
■■ “Microbiome, inflammation and cancer” by
Giorgio Trinchieri, NCI-Frederick, Frederick, Md.
■■ “Innate immunity and cancer” by Todd A.
Fehniger, Washington University School of
Medicine, St. Louis
■■ “Neoantigens and immunotherapy of cancer” by Ton Schumacher, Netherlands Cancer
Institute, Amsterdam
■■ “Checkpoint inhibitors and clinical application in melanoma” by Jeffrey S. Weber,
Moffitt Cancer Center and Research Institute
■■
Computation and
Functional Modeling
of Hot Big Data
Saturday, April 18, 10:15 a.m. to 12:15 p.m.
In recent years, we have experienced a spectacular increase
in the power and versatility of
both analytical and modeling
platforms. This ranges from new
technologies to decipher nucleic
acid sequences and identify proteins at great depth and decreas-
ing cost, to effective methods to
functionally mine the genome in
vitro and in animal models. The
typical output of such approaches
is so-called Big Data, which comes
with several challenges.
The topic that the speakers in
this session will cover is the functional annotation of Big Data. For
example, you will get insight into
data-driven identification of synthetic lethality networks to identify cancer-specific vulnerabilities
on a genome-wide scale. Speakers will discuss high-throughput
shRNA and CRISPR-Cas9 genetic perturbation screens in vitro
and in vivo, aiming to uncover
novel cancer genes as well as
targets amenable to therapeutic
intervention. Finally, large-scale
mouse knockout programs will be
presented that allow for identification of tumor modifiers. There
will be a brief discussion after each
presentation.
Chairperson: Daniel S. Peeper, Netherlands Cancer Institute, Amsterdam
■■ “Analyzing large genomic, phenotypic and
clinical data identifies novel syntheticlethal
cancer drug targets” by Eytan Ruppin, Center
for Bioinformatics and Computational Biology, College Park, Md.
■■ “Large-scale genetic screens in mice: Pathways, drivers and drug resistance” by David
J. Adams. Wellcome Trust Sanger Institute,
Cambridge, Mass.
■■ “Genome-scale CRISPR/Cas9 screening:
Technology and applications” by Neville
Sanjana, Broad Institure of MIT and Harvard,
Cambridge, Mass.
■■
Pan-Cancer Analysis
of Whole Genomes
Sunday, Apr 19, 1 p.m. to 3 p.m.
The Pan-Cancer Analysis of Whole
Genomes (PCAWG) project of the
International Cancer Genome Consortium and The Cancer Genome
Atlas is coordinating analysis of
more than 2,000 whole cancer
genomes. Each genome is characterized through a suite of centralized algorithms, including alignPLENARY CONTINUED ON PAGE 25
SHOW
For more information, visit www.DDN-News.com
PLENARY
CONTINUED FROM PAGE 24
ment to the reference genome,
standardized quality assessment
and calling of all classes of somatic
mutation. Scientists participating in the research projects of
PCAWG are addressing a series of
fundamental questions about cancer biology and evolution based on
these data, a sample of which will
be presented at this session.
Key areas of study include discovery of driver mutations outside
of the protein-coding regions of
the genome; integrating mutational signatures across tumor types
and mutation categories; characterizing subclonal structures
and patterns of genome evolution
across cancers; investigating relationships between germline and
somatic mutations; and investigating biological pathways targeted by driver mutations. There
will be a brief discussion after each
presentation.
Chairperson: Peter J. Campbell, Wellcome Trust Sanger Institure, Cambridge, U.K.
n■ “Cancer genome analysis in the cloud:
Technical, ethical and legal challenges” by
Lincoln Stein, Ontario Institute for Cancer
Research, Toronto
n■ “Investigation of germline genetic variation
in 2,500 whole cancer genomes” by Jan Korbel, European Molecular Biology Laboratory,
Heidelberg, Germany
n■ “Pathways and Drivers in 2,000 cancer
genomes” by Joshua M. Stuart, University of
California, Santa Cruz
n■ “Structural variation in 2,000 cancer
genomes” by Peter J. Campbell, Wellcome
Trust Sanger Institute
n■
Chairperson: Giorgio Trinchieri. NCIFrederick, Frederick, Md.
n■ “The microbiota in carcinogenesis and cancer therapy” by Giorgio Trinchieri
n■ “Microbial-driven cytokine expression fuels
colorectal cancer progression” by Sergei
I. Grivennikov, Fox Chase Cancer Center,
Philadelphia
n■ “Microbial activities promote development
of CRC” by Christian Jobin, University of
Florida, Gainesville
n■ “Ipilimumab and gut microbiota: Novel
aspects of immunotherapy” by Laurence Zitvogel, Institute Gustave-Roussy, Villejuif, France
n■
Liquid Biopsy Approaches
for Detecting, Monitoring
and Characterizing
Human Cancer
Tuesday, Apr 21, 1 p.m to 3 p.m.
Analyses of cancer genomes have
revealed mechanisms underlying
tumorigenesis and new avenues
for personalized therapeutic intervention. Nevertheless, there is
great complexity in the alterations
of individual tumors and a realization that these can change during
disease progression. This session
MARCH 2015 | | DDNEWS 25
will focus on new technologies that
have emerged to analyze molecular alterations in the circulation of
cancer patients, including as circulating tumor cells, cell-free tumor
DNA and exosomal nucleic acids.
These approaches have important
implications for noninvasive detection and monitoring of human cancer, therapeutic stratification and
identification of mechanisms of
resistance to targeted therapies.
n■
Chairperson: Victor E. Velculescu, Johns
Hopkins Kimmel Comprehensive Cancer
Center, Baltimore, Md.
“Characterization of circulating tumor cells”
by Daniel A. Haber, Massachusetts General
Hospital, Charlestown
n■ “SY37-02: Monitoring tumor evolution by
whole-genome plasma sequencing” by
Michael R. Speicher, Ellen Heitzer, Peter Ulz
and Jochen B. Geigl, Medical University of
Graz, Austria
n■ “Exosomes: Next generation diagnostics”
by Johan Skog, Exosome Diagnostics Inc.,
New York
n■ “Liquid biopsy approaches for characterizing
cancer genomes” by Victor E. Velculescu n
n■
“ cancer metabolism research
WE’RE BRINGING A NEW PERSPECTIVE TO
XF technology provides the easiest and most comprehensive
assessment of cancer cell metabolism, measuring glucose
and glutamine metabolism, and fatty acid oxidation of cancer
cells in a microplate, in real time!
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Microbiome
and Tumor Immunity
Monday, Apr 20, 1 p.m. to 3 p.m.
Commensal microorganisms colonize barrier surfaces of all multicellular organisms. For more than
500 million years, commensal
microorganisms and their hosts
have coevolved and adapted to each
other. As a result, the commensal
microbiota affects many immune
and non-immune functions of its
host, and de facto, the two together
comprise one metaorganism.
Microbial imbalance may play a
critical role in the development of
multiple diseases. The commensal
microbiota affects the development, progression and immune
evasion of cancer, but it has also
important effects on the response
to cancer immune therapy and
chemotherapy.
Tumor-associated myeloid cells
play a dual role inducing antitumor immune responses but mostly promoting immune evasion,
tumor progression and metastases
formation. Myeloid cells respond
to signals derived from commensal microbes that modulate their
function and reactivity in inflammation and their ability to act as
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adaptive immunity, thus affecting
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Experimental Group
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AACR 2015
26 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
Technology at the annual meeting
CREDIT: © 2014 AACR/TODD BUCHANAN
T
HE AACR IS dedicated to
bringing attendees the
latest innovations in
mobile technology to
enhance and facilitate
their annual meeting experience,
offering the following technology
products and services:
Free wireless internet access will
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HTC Touch Pro and Blackberry
Curve/Storm/Pearl).
Mobile Proceedings: The digital
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accepted for presentation as well as
the extended abstracts submitted
A view of the entrance to the AACR Annual Meeting 2014’s exhibits.
Exhibitors this year will include a wide array of companies with the latest
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Save, Share, Make Notes. You
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AACR Video App, downloadable
for the iPhone, iPad and Android
devices. Learn more at www.
AACR.org/videoapp. n
■■
■■
■■
■■
■■
■■
■■
■■
Continuing Medical Education (CME)
Credit Designation Statement
The AACR has designated this live
activity for a maximum of 45.5
AMA PRA Category 1 Credit(s).
Physicians should only claim credit
commensurate with the extent of
their participation in the activity.
Credit certification for individual sessions may vary, dependent upon compliance with the
ACCME accreditation criteria.
The final number of credits may
vary from the maximum number
indicated above.
Claiming (CME) Credit
Physicians and other health care
professionals seeking AMA PRA
Category 1 Credit(s) for this
live continuing medical education activity must complete the
CME Request for Credit Survey
by Wednesday, June 3, 2015.
Certificates will only be issued to
those who complete the survey.
Your CME certificate will be sent to
you via email after the completion
of the activity.
Statement of Educational
Need, Target Audience and
Learning Objectives
New technologies, scientific
advances and exponential developments in the field of translational
cancer medicine have led to changes in oncology practice and significant patient benefit. By bridging
the gap between what physicians
understand about cancer biology
and the clinical applications, this
meeting aids basic researchers,
physicians and clinician-scientists
in obtaining, synthesizing and
integrating the most cutting-edge
research. This exposure is essential for the implementation of best
practices, such as the most current
molecular-based tests to aid in the
diagnosis, treatment and prevention of cancer. Through the active
participation of clinical investigators and physicians in the meeting,
laboratory researchers will obtain a
better understanding of the wider
context of their research in the
“bench-to-bedside” continuum.
After participating in this CME
activity, physicians should be able to:
Identify technological advances
and tools to accelerate progress in
cancer research, improve early
detection and early intervention,
with the ultimate goal of extending
patients’ lives and improving their
■■
cal research efforts towards the
prevention and early detection
of cancer.
Develop collaborations
amongst physicians, researchers
and clinician-scientists to advance
the cause of treating and preventing cancer.
■■
CREDIT: B. KRIST FOR VISIT PHILADELPHIA
Accreditation Statement
The American Association for Cancer Research is accredited by the
Accreditation Council for Continuing Medical Education (ACCME)
to provide continuing medical education activities for physicians.
Opened in June 1993, the Pennsylvania Convention Center in Philadelphia
boasts famed landmarks within short walks of the facility, including
Independence Hall, Chinatown and Rittenhouse Square. Outside of the
western entrance is the Museum Mile, which stretches along Benjamin
Franklin Parkway.
quality of life.
Explain the integration of
information from basic and translational sciences to drug development, clinical research and application of new findings.
Integrate the use of biomarkers and other indicators to improve
patient selection (or stratification)
■■
■■
for clinical trials.
Incorporate the latest research
findings regarding therapies and
treatment options including
immunotherapy in a variety of
cancer types in order to improve
patient outcomes.
Formulate new strategies that
will further scientific and clini■■
■■
Disclosure Statement
It is the policy of the AACR that
the information presented at AACR
CME activities will be unbiased
and based on scientific evidence.
To help participants make judgments about the presence of bias,
the AACR will provide information
that Program Committee members
and speakers have disclosed about
financial relationships they have
with commercial entities that
produce or market products or
services related to the content of
this CME activity. This disclosure
information will be made available
in the program/proceedings of this
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Acknowledgement
of Financial or Other Support
This activity is supported by grants
and will be disclosed at the activity.
Questions about CME?
Please contact the Office of CME at
(215) 440-9300 or [email protected] n
AACR 2015
CREDIT: B. KRIST FOR VISIT PHILADELPHIA
AACR 2015 Cancer
and Biomedical
Research Career Fair
SATURDAY, APRIL 18, 9 A.M. TO 3 P.M.
Scientists at all levels are invited to
attend the AACR Career Fair during the annual meeting. The fair will
enable job seekers to connect with
EARLY
EXPOSURE
E
ARLY-CAREER SCIENTISTS were invited to apply
to give a talk in a Major
Symposium or Recent
Advances Session at the
AACR Annual Meeting 2015. Speaking slots are limited and available
to all AACR associate members and
any AACR active members who
are at the junior faculty level (not
higher than assistant professor or
equivalent). This program debuted
in 2014 with five AACR NextGen
Stars giving short talks in major
sessions. The NextGen Stars
program provides an opportunity to
increase the visibility of early-career
scientists at the AACR Annual Meeting and to support the professional
development and advancement of
those selected to speak.
NextGen Stars for 2015 will
receive travel support and
complimentary registration for
the meeting. n
Exhibit
Show Hours
SUNDAY, APRIL 19
1 p.m. to 5 p.m.
MONDAY, APRIL 20
9 a.m. to 5 p.m.
TUESDAY, APRIL 21
9 a.m. to 5 p.m.
employers from government, industry and academia. Representatives
from prospective employers will be
available to interview job seekers. n
MARCH 2015 | | DDNEWS 27
Robert Indiana’s iconic Love sculpture is located in the JFK
Plaza across from City Hall. It was installed in 1976, and its
location, JFK Plaza, is now better known as Love Park.
CREDIT: © 2014 AACR/TODD BUCHANAN
For more information, visit www.DDN-News.com
The poster presentation area at the AACR Annual Meeting
2014 is pictured here. Poster sessions at the 2015 meeting
will be located adjacent to the exhibitor area.
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2/19/2015 9:37:53 AM
28 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
CLINICAL TRIALS
WALTHAM, Mass.—Biopharmaceutical company
Minerva Neurosciences Inc. recently released preliminary results from a Phase 1 clinical study that demonstrated that treatment with MIN-202, a selective
orexin-2 antagonist, produced significant improvements in sleep onset and sleep duration in patients
with comorbid insomnia related to major depressive disorder. The company also shared preliminary
results from two other Phase 1 studies that suggest
the compound is well tolerated, with positive pharmacokinetic and pharmacodynamic features. Janssen
Research and Development LLC, one of the Janssen
Pharmaceutical Companies of Johnson & Johnson,
conducted the studies as part of a collaboration to
develop MIN-202. Sleep disturbances have been
linked to a suboptimal response to antidepressants
in patients with mood disorders, which leads to an
increased risk for relapse and prodromal depression.
Myriad RBM, Institut
Pasteur set sights on TB
SALT LAKE CITY—Myriad RBM, a wholly owned subsidiary of Myriad Genetics Inc., has teamed up with
the Institut Pasteur in a public-private research collaboration taking aim at tuberculosis. The partners
will conduct a proof-of-concept study to evaluate
patients with latent and active tuberculosis infections who are affiliated with the South African
Tuberculosis Vaccine Initiative clinical study sites.
The aims of the study will be to field-test Myriad
RBM’s TruCulture system as a point-of-care blood
collection and immune response monitoring method
and to stratify patients with active and latent tuberculosis. Matthew Albert, co-coordinator of Milieu
Interieur and director of the Immunology Department at Institut Pasteur, noted that, “Prior studies
support the use of the TruCulture system in settings
with limited resources, and may help us improve the
diagnosis of TB and accelerate the development
of new drugs and vaccines to treat the disease.”
IN
IN THIS
THIS SECTION
SECTION
Alzheimer’s disease
Head
Treatment to target tangles.................... 28
Text����������������������������������������������������������� 0
Fabry disease
Text............................................................
A fine showing for migalastat in Fabry... 280
Head
Insomnia
Text�����������������������������������������������������������
0
Orexin-2 antagonist
Text............................................................
yields
positive Phase 1 data.................... 280
Oncology
‘Catapulting’ forward with MultiStem.... 30
Double, double; myeloma in trouble?..... 28
Respiratory
Myriad RBM, Institut
Pasteur set sights on TB.......................... 28
Trial optimization
Optimizing trials through
mobile health technology........................ 32
A fine showing for migalastat in Fabry
Amicus reports positive Phase
3 data from a pair of studies
BY KELSEY KAUSTINEN
CRANBURY, N.J.—Biopharmaceutical com-
pany Amicus Therapeutics has released positive data on prespecified patient-reported
outcomes from both of its Phase 3 studies of
migalastat HCl, an oral small-molecule pharmacological chaperone for Fabry disease. The
company presented the data at WORLDSymposium 2015 in Orlando, Fla.
The first study, Study 011 (FACETS),
was a Phase 3 study measuring the reduction of disease substrate (globotriaosylceramide, or GL-3) in Fabry patients with
amenable mutations after treatment with
migalastat. The study also evaluated clinical outcomes such as renal function and
left ventricular mass index (LVMi) as
secondary endpoints. Patients enrolled
in this study were treatment-naïve or had
not received enzyme replacement therapy for at least six months prior to joining
the study. In Study 011, the recent data
reported improvements in gastrointestinal
symptoms, including a significant decrease
CREDIT: NASDAQ
Orexin-2 antagonist yields
positive Phase 1 data
Representatives of Amicus gather for the closing bell of NASDAQ on Feb. 28, 2014. The
company recently reported positive patient-reported outcomes on gastrointestinal symptoms,
pain and quality of life from two Phase 3 studies of migalastat in Fabry disease.
in diarrhea in patients receiving migalastat vs. placebo, and after 18 to 24 months
of treatment with migalastat, significant
improvements in diarrhea and indigestion
were seen, as well as promising trends in
reflex and constipation.
Study 012 (ATTRACT) was a Phase 3,
open-label study comparing oral migalastat
to standard-of-care enzyme replacement
therapies for Fabry disease (Fabrazyme and
Replagal). Patients in this study had Fabry
AMICUS CONTINUED ON PAGE 29
Double, double;
myeloma in trouble?
Genmab announces preliminary results
in Phase 2 study of daratumumab in
double refractory multiple myeloma
BY LLOYD DUNLAP
COPENHAGEN, Denmark—
er’s disease (AD), but nobody has
an approved treatment to target
the tangles at the moment, according to Dr. Claude Wischik,
Genmab A/S has announced
preliminary results from the
Phase 2 study of daratumumab in double refractory multiple myeloma conducted by
its collaboration partner Janssen Biotech Inc. The overall “We are very pleased with
response rate (ORR) in the these positive results in this
study was 29.2 percent in study of daratumumab as a
for the
the 16 mg/kg dosing group, monotherapy
treatment of double refractory
and the median duration of multiple myeloma,” says Dr.
response was 7.4 months as Jan van de Winkel, CEO of
determined by an indepen- Genmab. “We look forward to
presenting additional data of
dent review committee.
The study evaluated mul- this trial at a key upcoming
tiple myeloma patients who medical conference this year.”
have received at least three different lines of therapy, including both a proteasome inhibitor and an immunomodulatory
agent (IMiD), or who are double refractory to a proteasome
inhibitor and an IMiD. (Examples of proteasome inhibitors
TAURX CONTINUED ON PAGE 30
GENMAB CONTINUED ON PAGE 31
Alzheimer’s disease is a major and growing problem worldwide, and
tau-based vaccines may offer a new and more effective way to treat the
disease in its early stages. Research and consulting firm GlobalData
estimates the market for such a vaccine could be upwards of $10 billion.
Treatment to
target tangles
TauRx demonstrates potential efficacy
of tau aggregation inhibitor therapy in
Alzheimer’s disease
BY ILENE SCHNEIDER
S I N G A P O R E — Ta n g l e s
of
neuronal fibers are correlated
with abnormalities in brain
scans of patients with Alzheim-
CREDIT: GENMAB
BRIEFS
CLINICAL TRIALS
For more information, visit www.DDN-News.com
AMICUS
CONTINUED FROM PAGE 28
disease with amenable mutations
in a clinical trial assay and had
been treated with enzyme replacement therapy for a minimum of 12
months prior to joining the study.
Co-primary outcome measures
were mean annualized changes
in estimated glomerular filtration
rate (GFR) and measured (iohexol)
GFR assessed by descriptive comparisons of migalastat and enzyme
replacement therapy over 18
months. Secondary outcome measures featured LVMi and a composite of Fabry-associated clinical
events (e.g. renal, cardiac or cerebrovascular). For the new Study
012 data, patient-reported outcome
measures of pain and quality of
life were reported, with measures
of both remaining stable when
patients switched from enzyme
replacement therapy to migalastat.
“We are pleased to present compelling new data at WORLDSymposium on patient-reported outcomes on gastrointestinal symptoms, pain and quality of life from
our Phase 3 studies. In addition to
the previously reported migalastat
Phase 3 data, it was also important
to assess the impact of migalastat
on some of the most commonly
reported symptoms which can
severely impact quality of life
for people living with Fabry disease,” John F. Crowley, chairman
and CEO of Amicus Therapeutics,
said in a press release. “These positive results, shown for the first
time today in both naïve and ERT
switch patients, add to the totality
of the data that suggest migalastat could be an important new
therapy in the treatment of Fabry
disease. These data also continue
to show the positive effects for
patients, owing, we believe, to
migalastat’s novel mechanism
of action in all key organs and
tissues of disease. We continue
to move forward rapidly to seek
regulatory approval.”
Previously reported Phase 3
data from both trials showed that
migalastat treatment led to reductions in disease substrate, stability
of kidney function and improvement in a key cardiac parameter in
patients with amenable mutations.
Amicus defines amenable mutations as having “an absolute increase
of 3 percent of wild-type alphaGal A enzyme activity and a relative increase of 20 percent when
exposed to migalastat in a cellbased in-vitro assay.” All patients in
Study 011 and 012 presented with
amenable mutations in the clinical
trial HEK assay. After enrollment,
Amicus developed a GLP HEK
assay with a third party to measure
the criteria for amenability with
more quality control and rigor,
and overall, based on results from
mutations tested in that assay, the
company believes approximately
30 to 50 percent of patients with
Fabry disease have mutations
MARCH 2015 | | DDNEWS 29
“These positive results, shown for the first time today in both
naïve and ERT switch patients, add to the totality of the data that
suggest migalastat could be an important new therapy in the
treatment of Fabry disease. These data also continue to show the
positive effects for patients, owing, we believe, to migalastat’s
novel mechanism of action in all key organs and tissues of disease.”
John F. Crowley, chairman and CEO of Amicus Therapeutics
amenable to migalastat.
Fabry disease, as defined by the
Genetics Home Reference, a ser-
vice of the U.S. National Library of
Medicine, is “an inherited disorder
that results from the buildup of a
particular type of fat, called globotriaosylceramide, in the body’s cells.”
The disease is caused by mutations
in the GLA gene, which provides
genetic instructions for the production of alpha-galactosidase A, an
enzyme that normally breaks down
globotriaosylceramide. The mutations alter the structure and function
of alpha-galactosidase A, preventing
it from breaking down globotriaosylceramide, which then builds up
in cells—particularly those lining
blood vessels in the skin and cells
in the kidneys, heart and nervous
system—and damages them. n
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LONDON— Aimed in part at situa-
ting the United Kingdom as a gateway
for regenerative medicine in Europe,
Edinburgh, Scotland-based Athersys Ltd.
and Cell Therapy Catapult, a not-forprofit located at Guy’s Hospital in London, announced recently that Athersys
was awarded an Innovate UK grant.
The grant—expected to provide up to
£2 million ($3 million) in support over
the course of three years—will support
a Phase 2a clinical study evaluating
MultiStem cell therapy on acute respiratory distress syndrome (ARDS)
patients. The study will be conducted
by Athersys at leading clinical sites in
the United Kingdom in conjunction
with Cell Therapy Catapult.
“We are pleased to receive this award
from Innovate UK and to work with
the Cell Therapy Catapult to conduct
this important study,” stated Dr. Gil
Van Bokkelen, chairman and CEO of
Athersys, in a news release announcing
the award and collaboration. “Both
organizations reflect a commitment
to be a driving force in healthcare
innovation and to establish the UK as
the leading gateway for the regenera-
TAURX
CONTINUED FROM PAGE 28
co-founder of TauRx Therapeutics Ltd.
Part of the reason for that, he believes,
is that a huge investment of money
and people’s careers has gone into
approaching AD with amyloid therapy.
Clearly, that approach is not working.
While current treatments for AD are
only able to ease symptoms temporarily, tau-based vaccines may offer a new
and more effective way to treat AD in
the early course of the disease, says an
analyst with research and consulting
firm GlobalData. The market could be
worth upwards of $10 billion.
“It takes an upstart biotech company
like us to break the mold and show that a
different approach is viable,” Wischik says.
TauRx Therapeutics is a spin-out
company from the University of
Aberdeen in Scotland, established
in Singapore in 2002 to develop new
treatments and diagnostics for a range
of neurodegenerative diseases. The
company’s tau aggregation inhibitor,
LMTX, which is currently in global
Phase 3 clinical trials for Alzheimer’s
and frontotemporal dementia, targets
aggregates of abnormal fibers of tau
protein that form inside nerve cells in
the brain, giving rise to tau tangles.
Recently, The Journal of Alzheimer’s
Disease published the results of the
first clinical trial of a Tau Aggregation
Inhibitor (TAI) in AD. This Phase 2
clinical trial, conducted by TauRx,
provided the basis and rationale for
subsequent Phase 3 clinical trials of a
Athersys will conduct, along with Cell
Therapy Catapult, a Phase 2a clinical
study at leading clinical sites in the
United Kingdom to evaluate MultiStem
cell therapy for acute respiratory
distress syndrome.
tive medicine field in Europe.”
“ARDS is a serious condition that
is ineffectively treated by current
standards of care, resulting in substantial
patient and healthcare system impact,”
Van Bokkelen added. “We believe that
MultiStem cell therapy may provide an
important new option for treatment
and has the potential to meaningfully
improve clinical outcomes for patients
that are extremely ill.”
William (B.J.) Lehmann, president
and chief operating officer of Athersys,
tells DDNews that ARDS “is a serious
condition, requiring ICU/ventilator
treatment, and occurs from a variety of causes that catalyze a substantial
inflammatory response that greatly
affects the lungs.”
The Phase 2a clinical study “will exp-
TAI in AD currently in progress.
“We believe that we can arrest
disease progression, hit the pause
button and possibly even use the
treatment preventatively,” explains
Wischik. “It’s a completely different
kind of treatment that acts on
neurodegeneration.”
Tangles were originally discovered
by Alois Alzheimer in 1906, and this
discovery gave the disease its name.
Tangles were found to be composed
of abnormal filaments largely made up
of a short fragment of the protein tau
in 1988 by Wischik and his colleagues.
Using Heiko Braak’s system for staging
tangle pathology, the TauRx team has
seen that the process of developing
tangles begins in a person’s fifties or
earlier, and spreads from one region of
the brain to another. The progression
of the disease goes through six stages
with a decline in mental function.
The double-blind dose-finding
Phase 2 clinical trial with the TAI,
which involved 321 patients in 16
clinical research centers in the
United Kingdom and one center in
Singapore, tested three doses of the
drug. The study met its predefined
primary efficacy endpoint at 24
weeks on the standard scale most
commonly used to measure cognitive decline in clinical trials (ADAScog) at the 138 mg/day dose. The
primary result was also supported
by benefit on two other clinical
scales. The effect sizes seen were
statistically significant and clinically
lore the safety and efficacy of MultiStem
treatment in the ARDS patient population,” Lehmann says. “We have not yet
disclosed the details of the study plan,
but this will come soon.”
“Based on our prior work, we hypothesize that the treatment will help bring
the inflammation under control rapidly
and assist in the healing of damaged lung
tissue,” he continues. “This should result
in better overall recoveries and reduce
time on the ventilator and in the ICU
setting. Our working in this area has
been limited to large animal models of
the condition, where we have seen good
benefit. Our work in other clinical areas
[such as graft-versus-host disease] suggests that we can have an impact in this
patient population.”
If the Phase 2a clinical study is
successful, “most likely we would
proceed with advanced clinical studies,
designed to advance us to filing for registration,” Lehmann says.
Keith Thompson, CEO of Cell Therapy Catapult, stated in a news release,
“Bringing advanced therapeutic clinical
trials to the UK is a key part of our strategy to accelerate the growth of the cell
therapy industry to generate health and
wealth. We are delighted to collaborate
with Athersys on this important trial.”
MultiStem cell therapy may provide
an important new option to treatment,
according to Thompson, who notes,
ATHERSYS CONTINUED ON PAGE 32
meaningful in moderate subjects
at 24 weeks. The clinical results
were also supported by brain scan
evidence of arrest of decline over
the same period in mild subjects at
the same dose. The beneficial effect
was sustained to 50 weeks in both
mild and moderate subjects at this
dose, with 90-percent reduction in
the rate of cognitive decline overall.
However, the surprising observation that the top dose of 228 mg/day
had reduced efficacy has taken TauRx
scientists four more years to unravel.
They discovered that the original formulation suffers from dose-dependent
impairment in absorption when taken
with food and developed an entirely
new form of the molecule that enables
direct absorption without need for
active conversion in the gut. It is better
absorbed, better tolerated and has fewer
side effects, according to Wischik, thus
enabling Phase 3 trials to test whether
an even higher level of efficacy can be
achieved without significant loss of tolerability and safety. The ongoing trials
are testing LMTX in the dosage range
of 150 to 250 mg/day.
First results from the clinical trials
are expected in the first half of 2016.
If the Phase 3 clinical trials confirm a
level of efficacy and safety similar to
that seen in the Phase 2 trial reported
in the Journal of Alzheimer’s Disease, a
treatment targeting the Tau aggregation pathology of AD could be on the
market as early as 2017. n
EDITCONNECT: E031517
CLINICAL TRIALS
For more information, visit www.DDN-News.com
GENMAB
ly, Genmab has a clinical pipeline
with both late- and early-stage programs and an innovative preclinical
pipeline.
Genmab’s technology base consists of validated and proprietary
next-generation antibody technologies—the DuoBody platform for
generation of bispecific antibodies
and the HexaBody platform that
creates effector function-enhanced
antibodies. The HexaBody platform
strengthens the killing ability of
antibodies while retaining regular
CONTINUED FROM PAGE 28
are bortezomib or carfilzomib,
and examples of IMiD agents are
pomalidomide or lenalidomide.)
This is the indication for which
daratumumab was granted Breakthrough Therapy Designation by
the U.S. Food and Drug Administration (FDA) in May 2013. In
August 2012, Genmab granted
Janssen Biotech an exclusive
worldwide license to develop and
commercialize daratumumab.
“We are very pleased with these
positive results in this study of
daratumumab as a monotherapy
for the treatment of double refractory multiple myeloma,” said Dr.
Jan van de Winkel, CEO of Genmab. “We look forward to presenting additional data of this trial at a
key upcoming medical conference
this year.”
This two-part study enrolled
124 patients. Part one of the study
defined an optimal daratumumab
regimen going forward, while part
two was an expansion, based on the
optimal regimen determined in the
first part. The primary objective of
structure and specificity. The technology has the potential to enhance
antibody therapeutics for a broad
range of applications in cancer and
infectious diseases.
The DuoBody platform is a platform for the discovery and development of bispecific antibodies that
may improve antibody therapy of
cancer, autoimmune, infectious
and central nervous system disease. Bispecific antibodies bind to
two different epitopes either on
the same or on different targets
MARCH 2015 | | DDNEWS 31
(also known as dual-targeting),
which may improve the antibodies’ specificity and efficacy in inactivating the disease target cells.
DuoBody molecules are reportedly
unique in combining the benefits
of bispecificity with the strengths
of conventional antibodies, which
allows DuoBody molecules to be
administered and dosed as other
antibody therapeutics.
The Genmab UniBody technology creates a stable, smaller antibody format. UniBody molecules
will inhibit or silence cells, but not
kill them, which could be an advantage in the treatment of certain diseases such as asthma or allergies.
Genmab’s deep antibody expertise
is expected to provide a stream of
future product candidates. Partnering of selected innovative product
candidates and technologies is a
key focus of Genmab’s strategy, and
the company has alliances with top
tier pharmaceutical and biotechnology companies. n
EDITCONNECT: 031518
CREDIT: GENMAB
Redefining Microplate Washing...Again. Genmab’s technology base
consists of the DuoBody platform
for generation of bispecific
antibodies and the HexaBody
platform for creating effector
function-enhanced antibodies.
the study was to define the optimal
dose and dosing schedule, to determine the efficacy of two treatment
regimens of daratumumab as measured by ORR and to further characterize the safety of daratumumab
as a single agent.
Daratumumab is a human CD38
monoclonal antibody with broadspectrum killing activity, which is
in clinical development for multiple myeloma. Daratumumab
targets the CD38 molecule, which
is highly expressed on the surface
of multiple myeloma cells. Daratumumab may also have potential
in other cancers on which CD38 is
expressed, including diffuse large
B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, acute myeloid leukemia, follicular lymphoma and mantle cell
lymphoma.
Genmab is a publicly traded,
international biotechnology company specializing in the creation
and development of differentiated
human antibody therapeutics for
the treatment of cancer. Founded
in 1999, the company currently has
one marketed antibody, Arzerra
(ofatumumab), for the treatment
of certain chronic lymphocytic
leukemia indications. Additional-
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CLINICAL TRIALS
32 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
Optimizing trials through mobile health technology
NEW YORK— Medidata Solutions Inc. a global provider of
cloud-based solutions for clinical
research in life sciences, recently
announced a strategic collaboration with Garmin International
Inc., a unit of Garmin Ltd.,
aimed at making clinical trials better.
By integrating Garmin’s vívofit activity
tracker with the Medidata Clinical Cloud,
Medidata says it is enabling its life-sciences
customers to make use of mobile
health (mHealth) devices with
the potential to enhance patient
engagement, data quality and
operational efficiencies in clinical trials.
Designed to be worn on a
person’s wrist round-the-clock, Garmin’s
vívofit measures steps taken, distance traveled, calories burned and hours slept. The
water-resistant device—which displays
fitness data through its always-on LCD
display—is being used by Medidata to capture patient data in clinical trials. According
to Medidata, the vívofit was chosen because
of the ease of use provided by its year-long
battery life, which can improve the convenience and speed associated with capturing
direct-from-patient data and, as such, has
the potential to increase compliance among
study participants in a clinical trial setting.
“We’re thrilled to be working with Garmin,
a company that shares our passion for innovation and our commitment to enhancing
people’s health and well-being,” said Glen
de Vries, Medidata’s president. “Integrating
the vívofit with the Medidata platform is
part of our ongoing efforts to unify mHealth
devices with cloud-based technologies in a
clinical trial setting. We believe these efforts
will result in better data, enhanced patient
experiences and more efficient trials.”
TOOLS &
TECHNOLOGY
The vívofit—with its year-long battery life and ability to record such data as steps taken,
distance traveled, calories burned and hours slept—could play a key role in enhancing the
capture of direct-from-patient data during clinical trials.
Medidata has built cloud-based infrastructure that enables life-sciences companies to
explore the use of mHealth technologies in
clinical research. This infrastructure gathers
data from devices worn by patients and integrates it with other traditional clinical data,
“Integrating the vívofit with the Medidata
platform is part of our ongoing efforts to
unify mHealth devices with cloud-based
technologies in a clinical trial setting.
We believe these efforts will result in better
data, enhanced patient experiences and
more efficient trials.”
Glen de Vries, president of Medidata
ATHERSYS
CONTINUED FROM PAGE 30
“Preclinical data suggests that MultiStem cells may have a protective effect by
shifting the physiological response from
pro-inflammatory to anti-inflammatory. In animal models, MultiStem cells
have demonstrated an ability to reduce
the severity of pulmonary distress, reduce alveolar edema and return lung
endothelial permeability to normal.”
Intravenous MultiStem treatment early
on, following the onset of the condition,
may ameliorate the initial hyperinflammation and reduce the fibrotic activity
that follows, thereby speeding the return
to and improving the likelihood of more
normal lung function and helping patient
recovery, he explains, adding that up to 45
patients will be recruited at six to eight
sites for the study.
“As part of our strategy, we are collaborating with a number of companies and
institutions, not all grant-funded,” Thompson said. ”We were successful partners in
three other projects in the same Innovate
UK program this year.”
Furthermore, the UK remains supportive of stem cell therapy.
including labs, vital signs, medical history
and adverse events. Medidata is currently
working with top life-sciences organizations
to explore the feasibility of using the vívofit
in clinical trials.
The data is pulled from the Garmin activity tracker in 15-minute increments and then
analyzed to evaluate its connection with
traditional clinical measures and determine
whether it can provide better insight into
patient health status or response to therapy.
“At Garmin, our mission is to develop
innovative technology that promotes healthy
and active lifestyles,” said Allison Swelin,
strategic partnership development manager
at Garmin International. “We’re excited to
see Medidata use the vívofit in their pursuit
to help the global life-sciences industry find
better, easier ways to collect data directly
from patients.” n
“ARDS is a serious condition that is ineffectively
treated by current standards of care, resulting in
substantial patient and healthcare system impact.
We believe that MultiStem cell therapy may provide
an important new option for treatment, and has
the potential to meaningfully improve clinical
outcomes for patients that are extremely ill.”
Dr. Gil Van Bokkelen, chairman and CEO of Athersys
“The government continues to remain
squarely behind regenerative medicine as
one of the eight great technologies of the
UK,” Thompson said. “The Cell Therapy
Catapult aims to develop a portfolio of
clinical activities that covers the range
of the sector, generating strong clinical
data and building supportive structures
for routes to market that will drive investment and value into the UK.”
Characterized by widespread inflammation in the lungs, ARDS can be triggered
by pneumonia, sepsis or other trauma
and represents a major cause of morbidity
and mortality in the critical care setting.
ARDS has significant implications, as it
prolongs intensive care unit and hospital
stays and requires convalescence in the
hospital and rehabilitation. There are
limited interventions and no effective
drug treatments for ARDS, making it an
area of high unmet clinical need with high
treatment costs. The medical need for a
safe and effective treatment of ARDS is
also significant due to its high mortality
rate. Annually, it affects some 33,000
patients in the United Kingdom and
400,000 to 500,000 patients in Europe,
the United States and Japan. n
EDITCONNECT: E031519
For more information, visit www.DDN-News.com
MARCH 2015 | | DDNEWS 33
DIAGNOSTICS
oncgnostics licenses
MDxHealth tech
IRVINE, Calif. & HERSTAL, Belgium—Recently, oncgnostics GmbH announced that it had received
a limited worldwide license to MDxHealth SA’s
methylation specific PCR (MSP) technology. Per
the license agreement, MDxHealth has granted
oncgnostics a limited, non-transferable, nonexclusive, worldwide license to its patented MSP
technology for diagnostic applications in cervical cancer, for which it will receive upfront and
milestone payments in return, as well as royalties
on net sales.
“oncgnostics is pleased to obtain a license to
MDxHealth’s proprietary epigenetic technology
for use in our cervical cancer diagnostics programs. This technology allows for the accurate
and sensitive assessment of DNA methylation
markers included in our first test GynTect, which
is intended for the early detection of cervical
neoplasias that may progress to cancer,” said Dr.
Alfred Hansel, CEO of oncgnostics.
BJI InoPlex test
gains CE marking
PARIS— Diaxonhit recently announced the
completion of the CE marking of its BJI InoPlex
diagnostic test, reportedly the first blood test
to aid in the diagnosis of prosthetic bone and
joint infections. The marking was completed on
schedule in late 2014, and the test is now ready
for commercialization, with a planned launch
date in the first quarter of this year directly
through InGen, Diaxonhit Group’s commercial
affiliate.
BJI InoPlex demonstrated 82.2-percent specificity and 75.9-percent sensitivity compared
to microbiological results from intraoperative
samples, which includes all types of targeted
staphylococci (the most common culprit in such
infections). Approximately 10 to 20 percent of
patients receiving joint replacements experience
pain or functional impairment, and it is imperative
to discern whether the cause is due to infection
or mechanical malfunction in order to properly
treat the issue.
IN THIS SECTION
Alzheimer’s disease
Amarantus: Positive Alzheimer’s data.... 33
Infection
BJI InoPlex test gains CE marking........... 33
Oncology
A boost for NGS diagnostics................... 33
Advancing NSCLC diagnosis
and treatment.......................................... 33
oncgnostics licenses
MDxHealth tech...................................... 33
Prediabetes
New study support for Metabolon.......... 34
Advancing NSCLC diagnosis and treatment
Biocept, Insight to evaluate
expression and mutation in
ALK therapeutic target
BY LLOYD DUNLAP
SAN DIEGO— Biocept Inc., a molecular
oncology diagnostics company specializing
in biomarker analysis of cell-free circulating
tumor DNA (ctDNA) and circulating tumor
cells (CTCs), and Nashville, Tenn.-based
Insight Genetics, a molecular diagnostic assay
developer, are collaborating on an enhanced
diagnostic for the expression and mutation
of ALK, a major therapeutic target in treating
non-small cell lung cancer (NSCLC).
Biocept and Insight Genetics will evaluate
the combination of both companies’ platform
technologies to enhance detection of ALK
status in NSCLC patients. Biocept’s proprietary technology will be used to capture and
analyze CTCs and ctDNA. Insight Genetics
will then utilize its technical expertise and
proprietary evaluation methods to determine
ALK expression and whether the gene has
mutated over the course of cancer treatment.
The initial aim is to better identify and
monitor patients who may benefit from exist-
ing ALK-based therapies as well as those that
may benefit from second-generation therapies
based on inhibitor resistance mechanisms.
“ALK is incorporated into the testing
guidelines for oncologists making treatment decisions in NSCLC patients,” notes
Biocept’s Raaj Trivedi, vice president of commercial operations. “ALK-positive patients
now have targeted treatment options with
FDA-approved drugs: Pfizer’s Xalkori (crizotinib) and Novartis’s Zykadia (ceritinib). We
are finding that many patients are still not
being tested to determine their ALK status
due to a lack of biopsy tissue. This lack of
information makes personalized treatment
decisions—either to use FDA-approved ALK
target drugs or to include an ALK-positive
patient in a trial for second- and third-generation therapies—much more difficult.”
Part of Biocept’s business model is to help
identify more patients for new and existing
therapies using a simple, blood-based liquid
biopsy when tissue biopsy is not available.
Biocept currently offers an ALK rearrangement test using circulating tumor DNA
found in a patient’s blood. “However, we
are always looking for other technologies
ALK CONTINUED ON PAGE 35
Biocept Inc. and Insight Genetics are working
together to create an enhanced diagnostic for
the expression and mutation of ALK, a
therapeutic target in the treatment of nonsmall cell lung cancer.
Amarantus: Positive
Alzheimer’s data
BY MEL J. YEATES
to bolster Roche’s sequencing
unit and accelerate its development of targeted next-generation
sequencing (NGS)-based diagnostics. “Roche believes focused
and high-quality next-generation
sequencing assays using blood
SAN FRANCISCO—Amarantus BioScience Holdings Inc. has
announced positive top-line results of its LP-002 study of the
Lymphocyte Proliferation Test (LymPro Test) blood diagnostic for Alzheimer’s disease (AD). The 140-subject study successfully demonstrated that multiple individual biomarkers
achieved statistically significant results in correctly distinguishing patients with AD from healthy controls.
“Not only is LymPro a consistent and reliable tool in diagnosing Alzheimer’s disease, having completed ‘fit-for-purpose’ assay
validation at Icon [which provides lab testing and biomarker
services], it may now be used to enrich inclusion criteria in
pharmaceutical clinical studies,” said Colin Bier, chief development officer of Amarantus Diagnostics. Biomarker services
using LymPro data will be available for investigational use only
in pharmaceutical therapeutic clinical development programs.
“LymPro represents an innovative approach to improving
the diagnosis of Alzheimer’s disease by measuring a fundamental aspect of disease biology,” said Gerald E. Commissiong,
president and CEO of Amarantus. “The fact that LymPro has
the ability to distinguish patients with early-stage AD from control subjects will be important to the pharmaceutical industry
engaged in Alzheimer’s research.”
LymPro has shown itself able to differentiate Alzheimer’s
disease from Parkinson’s and vascular dementias with a sensitivity of 94 percent and specificity of 65 percent. This finding
ROCHE CONTINUED ON PAGE 34
LYMPRO CONTINUED ON PAGE 35
CREDIT: ROCHE
BRIEFS
For the Roche Sequencing Unit (pictured here), Signature’s most
valuable asset may be its large tumor tissue and plasma biobanks that
cover multiple cancers, including colorectal and lung cancer.
A boost for NGS
diagnostics
Roche expands sequencing unit with
acquisition of Signature Diagnostics
BY ZACK ANCHORS
PLEASANTON, Calif.— Roche
has extended its recent run of
acquisitions with the purchase
of Signature Diagnostics AG, a
privately held German translational oncology and genomics
company. The move is intended
DIAGNOSTICS
34 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
New study support for Metabolon
Recent study results
reinforce the clinical
validity of the
company’s IGT test
BY KELSEY KAUSTINEN
Metabolon’s Quantose IGT test
recently appeared in the Journal
of Diabetes Science and Technology,
supporting the clinical validity
of the test for assessing impaired
glucose tolerance (IGT), a state of
prediabetes. Quantose IGT is a laboratory-developed test that reflects
the degree of impaired glucose tolerance, a core metabolic defect
in dysglycemia and a known risk
factor for developing diabetes and
cardiovascular disease.
“This study verified that the
Quantose IGT test accurately
reflects IGT, which may provide
the opportunity for earlier clinical
intervention that could help curb
the epidemic of type 2 diabetes,”
Eric Button, senior vice president
of diagnostics at Metabolon, noted
in a press release. “We look forward
to bringing this new test to the market in the coming months.”
The test is designed to enable
physicians to easily identify IGT
using a single, fasted blood draw, a
simpler, less unpleasant approach
than the oral glucose tolerance test
(OGTT), the current clinical practice standard for measuring IGT.
The OGTT is a somewhat involved
process, requiring patients to fast
prior to the test, undergo a blood
draw to determine a fasting glucose
level and then drink a glucose-rich
beverage and undergo multiple
blood draws over the course of
ROCHE
CONTINUED FROM PAGE 33
samples have the capacity to
become cost-effective diagnostic
tools for monitoring patients with
cancer,” Dan Zabrowski, head of
Roche Tissue Diagnostics and
the Roche Sequencing Unit, tells
DDNews. “We plan to leverage Signature’s unique expertise in both
biobanks and cfDNA (cell-free
DNA) tests to develop targeted
diagnostics in the future.”
Signature’s most valuable asset
for Roche may be its large tumor
tissue and plasma biobanks that
cover multiple cancers, including colorectal and lung cancer.
The company has created these
biobanks within the framework
of large multicenter prospective
clinical studies. Among its key
products are longitudinal plasma
samples from cancer patients.
Zabrowski explains that Roche
sees high-quality, comprehensive
CREDIT: METABOLON
RESEARCH TRIANGLE PARK,
N.C.— Results from a study of
Metabolon recently announced additional results supporting the clinical validity of its Quantose IGT test, which
could offer a more convenient alternative to the current standard oral glucose tolerance test.
roughly two hours.
Button explains that the OGTT
currently stands as the standard for
checking the blood glucose levels
of pregnant women, specifically if
a glucose screening test result is
higher than normal and there is
a concern about gestational diabetes. However, while there are
approximately three million births
in the United States each year, he
says, fewer than a million tests
are performed for OGTT due to
its inconvenience.
“From the patients’ perspective, it goes beyond just a level of
inconvenience,” adds Doreen Bates,
senior director of marketing at
Metabolon. “Many people who’ve
had to take this test end up with
nausea, upset stomach, that kind
of thing, because they go in fasted,
and then they take blood draws.
They do the test, you have to sit in
the doctor’s office for those two or
three hours, so there’s a physical
and an inconvenient element to it
as well.”
Button tells DDNews that while
OGTT is also the current standard
when it comes to diagnosing diabetes, that is another instance in
which physicians pass over the
test given how time-intensive and
taxing it is.
“If one had a simple blood test
that could replace OGTT, it would
be used frequently as the convenient, gold-standard diabetes test,”
he notes.
Using its metabolomic profiling
technology, Metabolon identified
several metabolites whose fasting
levels are associated with both dysglycemia and type 2 diabetes, which
form the basis of its Quantose IGT
test. The test was developed using
fasting plasma samples taken just
cancer biobanks as holding great
potential when matched tumor tissue and plasma samples are combined with extensive clinical annotation. The company believes that
such a resource could lead to the
development of assays that identify the causes and mechanisms of
resistance to treatment and disease
recurrence.
“Having access to such unique
biobanks is a key component in the
development of novel NGS diagnostics,” says Zabrowski.
In addition to its biobanks, Signature has already developed several next-generation sequencing
assays using targeted gene panels
that are used for research purposes.
The company has built expertise in
developing ultra-deep sequencing
tests that utilize cfDNA.
Roche hopes that its effort to
develop effective NGS diagnostics
will benefit from Signature’s expertise in both biobanks and cfDNA
testing. “Biobanks play an impor-
tant role in uncovering the cause
or origin of disease such as cancer, which is important in translational research and the development of personalized therapies for
patients,” said Roland Diggelmann,
chief operating officer of Roche
Diagnostics, in an official statement. “Signature represents a
unique bridge between high-value
cancer biobanks and NGS assay
development.”
Signature was founded in 2004
and is currently based in Potsdam,
Germany. It appears that the firm
will continue to operate much as
it has previously under the corporate umbrella of Roche. Signature
will be integrated into the Roche
Sequencing Unit and will continue
to focus on expanding its genomic
signature portfolio. “Signature is
a strong company with excellent
management,” says Zabrowski.
“We plan to engage in a limited
integration and expect Signature
will act as a standalone enter-
prise.” Neither company has disclosed the financial terms of the
acquisition.
“We are very pleased Roche
recognizes the importance of
high-quality longitudinal cancer
biobanks for the development of
novel NGS-based diagnostics,” said
Andre Rosenthal, CEO of Signature, in the news release about the
deal. “Joining forces with Roche is
very exciting, as it will allow us to
further develop our NGS assays
for sequencing tests using cfDNA,
which may advance the development of non-invasive treatment
response monitoring for cancer
patients.”
The purchase of Signature is
just one of several recent acquisitions by Roche. Within the last
year it has also purchased Intermune, Genia Technologies, Santaris, Seragon Pharmacueticals and
Bina Technologies. The Swiss firm
recently posted a 16-percent drop
in annual profits for 2014 but pre-
prior to an OGTT from 1,623 nondiabetic subjects from two different cohorts: 955 from the Relationship between Insulin Sensitivity
and Cardiovascular Disease Study
(RISC Study; 11.7 percent IGT)
and 668 subjects from the Diabetes
Mellitus and Vascular Health Initiative cohort from the DEXLIFE
project (11.8 percent IGT).
Button says that the Quantose
IGT test offers a more accurate
approach, because the sugar solution that has to be drunk with the
OGTT “adds a lot of unknown variables,” an issue Bates echoes.
“We’re measuring what’s going
on within a person’s body as it’s
actually occurring, without, as Eric
said, that artificial adjustment from
the sugar drink that you have to
take when you do the oral glucose
tolerance test; that’s artificially
adjusting your body to stress it in
some ways, and we’re not doing
that. We’re just measuring what’s
happening in your body as it’s
occurring currently,” she explains.
As the company advances the
Quantose IGT test, Button says
they will be conducting additional
studies to support its clinical utility, in addition to seeking reference laboratory partners to aid in
the nationwide distribution of the
test. In the third quarter of 2014,
Metabolon announced a partnership with Metadia Biotech S.L. to
commercialize its Quantose IR
and Quantose IGT prediabetes
tests in Europe (for more information, check out “Metabolon taps
Metdia for European marketing
of prediabetes test” in the Diagnostics section of our November
2014 issue). n
EDITCONNECT: E031523
dicted profits and sales to increase
significantly in 2015.
While Roche’s recent acquisitions may fit into a broader strategy
for the company, the merger with
Signature also serves the more
specific goals of the company’s
sequencing unit. “The strategy for
Roche Sequencing is to advance
NGS through an integrated genomics portfolio that provides our
customers with a complete, endto-end testing solution,” Zabrowski
tells DDNews. “To this end, we are
focused on developing an NGS
workflow solution encompassing
four key areas: sample preparation, platforms and technology,
informatics and diagnostic testing menu.” Zabrowski says the
sequencing unit is making significant internal investments in potential breakthrough technologies as
well as seeking innovative technologies that are being developed
by other companies.
EDITCONNECT: E031521
DIAGNOSTICS
For more information, visit www.DDN-News.com
LYMPRO
CONTINUED FROM PAGE 33
is important, as it could assist
pharmaceutical companies in
distinguishing dementia of the
Alzheimer’s type from dementia
of a disparate etiology.
Amarantus has also identified a new, undisclosed biomarker that correlates with
AD diagnosis in the LP-002
study. This new marker could
become a component of a
multivariate algorithm (LymPro Score) which will create
a simplified assessment of a
person’s probability of having
Alzheimer’s disease. Commissiong tells DDNews, “The
newly identified biomarker
will impact the sensitivity of
the assay and possibly improve
the specificity of the test’s
diagnostic capabilities.”
Amarantus has also
announced its first Alzheimer’s biomarker services collaboration with Anavex Life
Sciences Corp. The investigational Alzheimer’s drug candidate ANAVEX 2-73 and drug
combination ANAVEX PLUS
will be used to evaluate the
pharmacodynamic effect on
biomarker CD69 in specific
subpopulations of peripheral
blood lymphocytes, using the
LymPro diagnostic. LymPro is
not the only test for Alzheimer’s currently in development,
but Commissiong believes
it has an advantage in that it
does not only identify people
with Alzheimer’s. Lympro is
a dynamic assay, which may
potentially assist in the development of therapeutic drugs
for Alzheimer’s patients.
“This is the type of collaboration that becomes possible
with new diagnostic tools to
help therapeutic interventions in AD. The mechanisms
involved may begin to validate
emerging targets in the field of
AD, and I am excited to help
bring this collaboration forward,” commented Dr. Robert A. Stern, director of the
Clinical Core of the Boston
University Alzheimer’s Disease Center.
ANAVEX 2-73 is an orally
available small molecule being
investigated for AD treatment.
ANAVEX 2-73 has preclinical
data indicating potential for
the drug to be able to prevent,
halt and/or reverse the course
of Alzheimer’s. The combined therapeutic ANAVEX
2-73 and donepezil (Aricept),
called ANAVEX PLUS, has a
promising synergistic effect:
ANAVEX PLUS produced up
to 80 percent greater reversal
of memory loss in Alzheimer’s
than individual usage of donepezil or ANAVEX 2-73. n
ALK
CONTINUED FROM PAGE 33
that will identify the full spectrum
of patients who might qualify for
existing therapies or therapeutic
candidates,” Trivedi states. “Our
hope is that by expanding our
menu to include different methods
of evaluating ALK status (such as
ALK expression) we will be able to
identify such patients.”
“We established this research
collaboration with Insight Genetics to identify and validate these
additional methods of determining ALK status—specifically, the
ALK kinase domain by mRNA
expression. Qiagen already offers
this Insight Genetics mRNA test
for tissue biopsies, so the logical
next step was for our companies
to work together to bring Insight’s
tissue-based offering to a less invasive, blood-based platform using
Biocept’s proprietary blood-based
detection technology.”
“As the field of ALK-based
therapies continues to grow with
MARCH 2015 | | DDNEWS 35
second- and third-generation molecules, the concept of looking at
both DNA and RNA from CTCs is
a diagnostic approach Insight has
been interested in exploring for
some time. Biocept, as a leader in
CTC and ctDNA capture and analysis, is well positioned to help us
pursue this diagnostic innovation,”
said Dr. Stephan Morris, chief scientific officer of Insight Genetics.
“The ability to obtain information about a tumor through a simple, blood-based test is appealing in
that it can not only qualify patients
for targeted therapies, but also aid
in the monitoring of these patients
for changes in a tumor as disease
progresses,” Morris continued. “By
combining our existing expertise in
ALK testing with Biocept’s liquid
biopsy technologies, we are poised
to expand our mutual efforts in profiling and monitoring ALK positive
patients and mechanisms of resistance identified with this patient
cohort.” n
EDITCONNECT: E031520
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ReproCELL is an expanding global leader in
providing researchers with integrated tools
for translational research. ReproCELL, with
its BioServe, Reinnervate and Stemgent
brands offers a comprehensive suite of products
and services from human biospecimen procurement
to 3D cell culture, through cellular reprogramming
and differentiation to readily-available
differentiated cells.
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EDITCONNECT: E031522
www.reprocell.com · www.bioserve.com · www.stemgent.com · www.reinnervate.com
36 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
BUSINESS &
GOVERNMENT POLICY
BR IEFS
Ontario Brain Institute
receives $56M investment
TORONTO—In hopes of supporting promising
research into diagnosing and treating brain disorders such as autism, depression, Alzheimer’s disease and Parkinson’s disease, Ontario has made an
investment of $56 million as part of its five-year,
$100-million commitment to the not-for-profit Ontario Brain Institute. The investment will be broken
down as follows: $25 million in renewal funding
to support work in the diagnosis and treatment of
cerebral palsy, epilepsy and neurodevelopmental
disorders such as autism; $12 million in new funding
to support work focused on the diagnosis and treatment of depression; and $19 million in new funding for research into the diagnosis and treatment
of Alzheimer’s, Parkinson’s, amyotrophic lateral
sclerosis and other neurodegenerative diseases.
Galapagos gains grant
for MRSA antibiotic
MECHELEN, Belgium—Galapagos NV recently received
a €2.5-million (approximately $2.8 million) grant
from the Flemish Agency for Innovation through Science and Technology to support Galapagos’ novel
antibiotics in a collaboration with Prof. Herman
Goossens, head of the microbiology laboratory at
the University of Antwerp (UA). The grant was for the
project “Partnering tiered clinical Phase 2 anti-MRSA
antibiotic with rapid diagnostic test development,” in
which Galapagos will collaborate with the Laboratory of Medical Microbiology of UA. Among Galapagos’ candidates is GLPG1492, a narrow-spectrum
antibiotic with a novel mode of action against all
Staphylococcus aureas strains, including MRSA. The
antibiotic has shown excellent antibacterial efficacy
and broad coverage of all known MRSA strains.
Valeant nabs
Dendreon for $400M
by Kevin Noonan
Supreme Court
revises patent
claim construction
review standards
Valeant will gain rights to Provenge and certain other assets
BY LLOYD DUNLAP
LAVAL, Quebec—Valeant Pharmaceuticals
International Inc. announced recently that it
had been advised by Dendreon Corp. that no
additional qualified bids have been received
by the bid deadline provided by the courtapproved bidding procedures for the sale of
substantially all of Dendreon’s assets. A hearing at which Dendreon and Valeant were to
seek the required court approval of the sale was
scheduled for Feb. 20, with Valeant expected
to close the transaction very soon thereafter.
Pursuant to the terms of the agreement,
Valeant will acquire the worldwide rights to
Dendreon’s Provenge (sipuleucel-T) product
and certain other Dendreon assets. Provenge
is an immunotherapy designed to treat men
with advanced prostate cancer by taking the
body’s own immune cells and reprograming
them to attack advanced prostate cancer. The
product was approved by the U.S. Food and
DENDREON CONTINUED ON PAGE 37
“We believe that
oncology has similar
characteristics to our
current therapeutic
portfolios, such as
strong growth, high
durability, strong
patient and physician
loyalty and a terrific
reimbursement regime.”
J. Michael Pearson,
chairman and
CEO of Valeant
T
deal, GSK will acquire a small number of
early-stage vaccines being developed against
bacterial infections such as pneumonia, Pseudomonas, Staphylococcus aureus and Shigella.
GlycoVaxyn was incorporated in 2004 as
a spin-off from ETH Zurich and specializes
in developing next-generation bioconjugate
vaccines against bacterial infection. The
company has an E. coli vaccine candidate in
Phase 1 clinical trials, and expects to begin
a Phase 1 trial for a shigellosis vaccine in
the United States in the first quarter of this
year, with financial support from the WellGSK CONTINUED ON PAGE 38
PATENT CONTINUED ON PAGE 40
CREDIT: GSK
GSK has bulked up its early-stage vaccine pipeline with the recent acquisition of Swiss
biopharma company GlycoVaxyn AG.
Boosting vaccine vitality
GSK bolsters vaccine
division with
GlycoVaxyn acquisition
BY KELSEY KAUSTINEN
LONDON—In a move that enhances its ear-
ly-stage vaccine pipeline, GlaxoSmithKline
plc (GSK) has acquired Zürich-Schlieren,
Switzerland-based GlycoVaxyn AG, a specialist vaccine biopharmaceutical company.
GSK has paid $190 million to purchase the
remaining stake in GlycoVaxyn, which is
valued at $212 million. Per the terms of the
HE U.S. SUPREME COURT
handed down an important patent decision
recently in Teva v. Sandoz,
changing the standards
used by the Court of Appeals for the
Federal Circuit that have been applied
for over a decade.
By way of background, a patent is
comprised of two interrelated parts:
the specification,
which describes the
invention in sufficient detail that
the skilled worker
will be able to
practice it after the
patent expires, and
the claims, which Kevin Noonan,
partner,
define the paten- McDonnell
tee’s legal right to Boehnen
exclude others from Hulbert &
making, using, sell- Berghoff LLP
ing, offering to sell
or importing the invention during the
patent term. The scope and meaning
of patent claims in litigation are determined by the trial court as a matter of
law, according to an earlier Supreme
Court decision (Markman v. Westview
Instruments). The Federal Circuit, in
deciding the standard of its review of
those trial court decisions in Cybor v.
FAS Technologies, adopted a completely
de-novo standard, wherein neither the
legal nor the factual determinations by
the trial court were given any deference.
The Teva case involved the meaning of the term “molecular weight” as
used in the claims. The trial court had
considered expert testimony regarding three meanings for the term used
in the art; these are the “peak average molecular weight” (Mp, defined
as the weight of the molecule that
is most prevalent in a mixture); the
“number average molecular weight”
(Mn, defined as the average weight
of all the different-sized molecules in
the mixture); or the “weight average
molecular weight” (Mw, determined
by calculating the average weight of
IN THIS SECTION
Antibiotics
Galapagos gains grant
for MRSA antibiotic................................. 36
Brain disorders
Ontario Brain Institute
receives $56M investment...................... 36
Patent claim review
Supreme Court revises patent
claim construction review standards...... 36
FDA approval/Orphan drug
Two orphans for OncoMed...................... 39
Genomics
Deciphering the language
of gene regulation................................... 40
M&A activity
Boosting vaccine vitality......................... 36
Roaring back…but more modestly
(HOSPIRA from cover).............................. 41
Valeant nabs Dendreon for $400M......... 36
Tools and technology
On the cutting edge................................. 38
Patent Docs
For more information, visit www.DDN-News.com
BUSINESS & GOVERNMENT POLICY
MARCH 2015 | | DDNEWS 37
DENDREON
CONTINUED FROM PAGE 36
Drug Administration (FDA) in April 2010
and realized revenues of approximately $300
million in 2014. Provenge was approved by
the European Medicines Agency in 2013.
Dendreon has been a debtor under chapter 11 of the U.S. Bankruptcy Code since
November 2014. The asset purchase agreement constitutes a “stalking horse bid” in a
sale process being conducted under Section
363 of the U.S. Bankruptcy Code. As the
“stalking horse bidder,” Valeant would have
been entitled to a break-up fee and expense
reimbursement if it ultimately did not prevail
as the successful bidder at a subsequent auction for Dendreon’s assets. Valeant’s role as a
stalking horse bidder, and the sale itself, are
subject to approval by the Bankruptcy Court.
“We believe that oncology has similar characteristics to our current therapeutic portfolios,
such as strong growth, high durability, strong
patient and physician loyalty and a terrific
reimbursement regime,” stated J. Michael Pearson, Valeant’s chairman and CEO. “We have
not previously found an economic way to enter
this market, but with the unique dynamics of
this situation, we believe that this transaction
will create significant shareholder value.”
Earlier, Valeant entered into an amended
and restated stalking horse asset purchase
agreement to acquire the worldwide rights
to Dendreon’s Provenge product and certain
other assets of Dendreon. At one point, Valeant raised its offer to $400 million in cash for
the assets, which realized combined revenues
of approximately $300 million in 2014. As it
happened, there was no auction, as Valeant
made the only bid for the Seattle company.
It was in late January that Valeant bid $296
million to set the baseline for a potential auction. Indications were that one would indeed
likely come, with Dendreon’s lawyers noting
in court papers that “several bidders” wanted
more time to put together potential offers.
Shortly thereafter, Valeant kicked up its
offer to $400 million. Whether that cooled
off any potential counter-bids or whether the
interest among other potential buyers wasn’t
what the lawyers thought, no one emerged
to challenge Valeant’s bid.
Acquiring Dendreon’s assets after the company went into bankruptcy adds Provenge for prostate cancer to Valeant’s portfolio.
For a while, Dendreon was a potential
jewel in Seattle’s biotech community, with
the company getting the first FDA approval
for a cell-based cancer immunotherapy in
2010. Provenge required extracting cells
from a patient, shipping them to a processing center, genetically engineering them and
shipping them back to be reinfused into the
patient—a logistical challenge, to be sure, but
one the company seemed to have a handle on.
Then things went wrong, with marketing
woes and concerns over the $93,000 price
tag and how that might be reimbursed. So
Provenge’s launch had an albatross around
its neck early on. Dendreon’s debt grew, and
other new prostate cancer drugs happily
took their place in the market at Dendreon’s
expense, among them Zytiga and Xtandi.
Provenge generated $300 million in sales
last year. Abiraterone, by comparison, gener-
PLAS ■ LABS, INC.
Although Valeant is known for its aggressive
strategy of inorganic growth through
acquisitions, this deal took some by surprise
as it was not a high-quality prospect with
lucrative assets such as Allergan, which
Valeant failed to take over last year.
www.PLAS-LABS.com
517-372-7177
[email protected]
ated $1.07 billion in the first half of 2014 alone.
Valeant’s business model has long been to
buy other drug companies to grow its portfolio rather than spend a lot developing its
own pipeline. But the Dendreon purchase
surprised some market watchers, partially
because Valeant is taking a totally different
tack than it did with its attempt to acquire
Allergan. While Allergan was considered a
high-quality pharmaceutical firm with lucrative products, Dendreon is quite the opposite.
But analysts’ opinions weren’t all negative.
Jefferies analyst David Steinberg raised estimates and his price target on Buy-rated Valeant to $179 (from $149) following updated fiscal 2015 guidance from the company. Steinberg commented on positive fiscal year 2015
forecasts with regard to revenue and earnings
per share (EPS), and despite “substantial
headwinds” that are expected to reduce rev-
enues and EPS by about $300 million, relative
to prior views after the third quarter of fiscal
2014, “New product launches, spearheaded
by Jublia, are taking center stage.”
Analyst Louise Chen at Guggenheim noted
several positives from a recent Valeant conference call: CEO compensation is more aligned
with shareholder value now and the CEO
signed a five-year contract, plus the company
is said to be well positioned for strong organic
growth in 2016, with seven or eight launches
and “best products” that include Vesneo, Brimonidine, Ultra platform and Emerade. She
added that Jublia peak sales could be over $750
million, though Valeant’s expectation is $300
million to $400 million for now.
Valeant made a much bigger deal after
this one, as DDNews was going to press. Read
more on that on page 42. n
EDITCONNECT: E031524
BUSINESS & GOVERNMENT POLICY
38 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
ON THE CUTTING EDGE
A roundup of
instrumentation,
software and other tools
and technology news
HIS MONTH, we take a look at
remote access for
life-sciences and
diagnostic products, a commitment to sequencing technology to help push
genomics forward in Scotland,
a lung cancer monitoring collaboration and
a cloud-based system for patient-centered
translational research.
TOOLS &
TECHNOLOGY
RealVNC licenses remote
access technology to Beckman Coulter
BREA, Calif.— This winter saw Beckman
Coulter, a world leader in in-vitro diagnostics, and Cambridge, U.K.-based RealVNC,
a global provider of VNC remote access
technology, announce that Beckman Coulter
will be licensing RealVNC’s technology. VNC
enables a computer user to remotely access
another computer or device in a secure and
reliable manner, and Beckman Coulter will
be deploying RealVNC’s top-end solution,
VNC, with an enterprise license to its lifesciences and diagnostics products to enable
it to efficiently support these systems.
In addition, Beckman Coulter will also
use RealVNC’s VNC Viewer SDK to create
its own viewer for iOS, which will enable
its technical support representatives to take
control of their systems remotely from an
iPad or iPhone, enabling reps the flexibility
to use the technology in the field and onsite.
“RealVNC’s technology and expertise will
allow us to enhance our products and the way
we serve our laboratory customers,” said John
Hetzler, software engineering senior manager
for workflow and IT solutions at Beckman
CREDIT: COOLCAESAR
T
BY JEFFREY BOULEY
Coulter Diagnostics. “The collaboration with
RealVNC will enable us to develop customized
technology that will enhance our IT solutions.”
“This is yet another great example of a
large organization leveraging the power of
VNC as part of a range of commercially available devices worldwide,” said Richard Pickul,
strategic alliances manager for RealVNC.
“We are delighted to be working
with Beckman Coulter to deliver
remote access capabilities to
their life-sciences and diagnostics products and continue to
look forward to expanding the
relationship in the future.”
Illumina seeks to help put Scotland
at forefront of gene-led healthcare
Beckman Coulter will be licensing RealVNC’s technology for support systems related to lifesciences and diagnostics products.
EDINBURGH & GLASGOW, Scotland—San
ship will initially focus on very rapid screening
of cancer patients, diagnosing childhood illnesses, disorders of the central nervous system
and population studies.
Prof. Jonathan Seckl, vice principal of
research at the University of Edinburgh,
said, “Scotland is uniquely placed to make
a significant contribution to the field of
genomics medicine. It has well-established
and approved methods of linking electronic
health records to medical research programs,
governed by NHS and academic regulations.
Edinburgh is also home to the U.K.’s national
supercomputer facility, which will provide
the high-performance data processing ability needed to analyze the vast volume of
information that will be generated from this
research. This affords an exceptional opportunity for Scotland’s outstanding researchers
and clinicians to transform the way medicine
is practiced in the coming years.”
“Scotland has an ideal ecosystem to lead the
world in precision medicine,” added Prof. Anna
Dominiczak, vice principal and head of the College of Medical, Veterinary and Life Sciences
at the University of Glasgow. “With a population of 5.3 million, cohesive and collaborative
Diego-based sequencing and genomics
company Illumina Inc. is partnering with
the University of Edinburgh and University of
Glasgow in a £15-million (about $23 million)
project with a goal to “secure Scotland’s place
as a world leader in a genomics revolution
that is set to transform healthcare.”
The initiative reportedly will enable scientists and clinicians to access equipment
that can decode the entire genetic makeup
of a person for less than £750 and study the
genomes of both healthy and sick people on
a large scale and faster than they have before.
The investment will establish the Scottish
Genomes Partnership, which will install 15
state-of-the-art Illumina HiSeq X sequencing instruments divided between two hubs
within the universities.
Linking genetic data with clinical information will enable more precise, molecular
diagnoses for patients in the Scottish National
Health Service (NHS), leading to more personalized treatment and safer selection of
drug therapies, the partners say, and will bring
new understanding of the causes of both rare
and common diseases, opening the door to the
development of new treatments. The partner-
GSK
come Trust. GlycoVaxyn brings with it 50
employees.
“This is an exciting opportunity to expand
our research efforts to develop a new generation of vaccines for common and severe
bacterial infections, for many of which
there are currently no effective vaccines,”
Dr. Moncef Slaoui, chairman of vaccines
at GSK, commented on the transaction. “It
reinforces our commitment to seek out and
invest in great science and complements our
proposed transaction with Novartis, which
will strengthen our leading position in vaccines.” (That transaction was completed
March 2 as this issue was going to press,
and with it GSK has, among other things,
acquired Novartis’s global vaccines business,
excluding influenza vaccines.)
This GlycoVaxyn deal builds off of an
existing relationship with GSK that began
in 2012. GlycoVaxyn announced Dec. 19,
2012, that it had begun a collaboration
with GSK Biologicals for the development
of new bacterial vaccines using GlycoVaxyn’s bioconjugation technology. The
CREDIT: GSK
CONTINUED FROM PAGE 36
“This is an exciting opportunity to expand our
research efforts to develop a new generation
of vaccines for common and severe bacterial
infections, for many of which there are
currently no effective vaccines,” says Dr.
Moncef Slaoui, chairman of vaccines at GSK.
agreement included an undisclosed set of
pathogen targets within the field of bacterial vaccines, and GSK had an option to
obtain an exclusive license on the targets
during the three years of the collaboration’s
duration and to extend both the length and
scope of the deal. In addition, GSK made an
upfront payment to GlycoVaxyn as well as
an equity investment in the company. GlycoVaxyn was eligible to receive milestone
payments and royalties on any licensed vaccine candidates.
“Since the spinoff from ETH Zurich, we
have successfully advanced our biological
conjugation technology and developed a
strong pipeline of vaccine candidates. We
are delighted to now work even closer with
one of the leading vaccine companies in the
world on the development of much-needed
vaccines,” said Michael Wacker, co-founder
and chief scientific officer of GlycoVaxyn.
GlycoVaxyn’s bioconjugation platform
enables the development and production of
immunogenic glycoprotein conjugates via
a biological process that bypasses many of
the challenges faced with current chemical
methods. The company notes that its platform “has broad potential applications in
the field of bacterial vaccines, but also in
viral and cancer vaccines and human therapeutic proteins.” The platform offers versa-
NHS, academia and industry, we have developed unique capability to screen DNA from
patients with cancer, rheumatoid arthritis and
other inflammatory and infectious diseases.”
“By unlocking the power of the genome,
we can better understand cancer and rare
diseases and ultimately transform how they
are diagnosed and treated,” said Jay Flatley,
CEO of Illumina.
Monitoring EGFR mutational
status in lung cancer patients
SAN DIEGO—Trovagene Inc. announced
recently that it has entered into a clinical
collaboration with California-based City of
Hope to conduct studies to determine the
clinical utility of detecting and monitoring
EGFR mutations in lung cancer patients
using Trovagene’s Precision Cancer Monitoring platform.
“Tracking various alterations in the EGFR
oncogene, particularly emergence of the
T790M mutation, has potential to improve
therapeutic strategies for treating patients
with non-small cell lung cancer,” said Dr.
Mihaela Cristea, lead investigator and assoEDGE CONTINUED ON PAGE 41
tility across many pathogens and conjugates
because it “enables the combination of any
polysaccharide antigen with any protein
antigen,” and also offers batch-to-batch consistency. GlycoVaxyn’s vaccines are highly
immunogenic, the company explains on its
website, because they “[express] polysaccharide epitopes in their most native (natural)
conformation and [combine] them with the
most immunogenic protein carriers also
in a well-defined and preserved natural
conformation.”
This is the latest move in GSK’s efforts
to boost its vaccines portfolio. Back in June
2014, GSK announced its three-part asset
swap with Novartis. Under that agreement,
GSK acquired Novartis’ global vaccines business, aside from influenza vaccines, for an
initial cash consideration of $5.25 billion,
with the potential for milestone payments
of up to $1.8 billion and ongoing royalties.
In conjunction with the acquisition, GSK
agreed to sell Nimenrix and Mencevax, its
meningitis vaccines, on a global basis, as
well as divesting two small Novartis bivalent
vaccines for protection against diphtheria
and tetanus in Italy and Germany. n
EDITCONNECT: E031525
BUSINESS & GOVERNMENT POLICY
For more information, visit www.DDN-News.com
MARCH 2015 | | DDNEWS 39
Two orphans for OncoMed
CREDIT: ONCOMED
Abraxane (albumin bound) plus gemcitabine
in first-line advanced pancreatic cancer
patients. The PINNACLE study is testing
tarextumab in combination with etoposide
and cisplatin and etoposide and carboplatin
in first-line extensive-stage small cell lung
cancer patients.
“Tumor Notch3 gene expression is estimated to be elevated in approximately 70
percent of pancreatic cancer patients, and
BY LLOYD DUNLAP
REDWOOD CITY, Calif.—OncoMed Phar- it is thought to be an indicator of poor progmaceuticals Inc., a clinical-stage company nosis and chemotherapy resistance,” noted
developing novel therapeutics that target Dr. Jakob Dupont, OncoMed’s chief medicancer stem cells (CSCs), or tumor-ini- cal officer. “The data suggesting that the biotiating cells, has announced that the U.S. marker-positive patients may have improved
response rates and survival with tarFood and Drug Administraextumab treatment are supportive
tion’s Office of Orphan Prodof the Phase 2 design of the ALPINE
ucts Development has granted
study, where tarextumab’s impact
Orphan Drug designation to
on efficacy of all patients enrolled
tarextumab (anti-Notch 2/3,
as well as the biomarker posiOMP-59R5) for the treatment
tive patients will be assessed. The
of both pancreatic cancer and
Notch3 predictive biomarker may
small cell lung cancer.
enable us to identify those patients
“We are excited to receive
that would gain the greatest benefit The U.S. Food and Drug Administration’s Office of Orphan Products Development has granted
two separate orphan drug des- “Tumor Notch3
Orphan Drug designation to tarextumab (anti-Notch 2/3, OMP-59R5) for the treatment of both
ignations for tarextumab for gene expression is from tarextumab treatment.”
pancreatic cancer and small cell lung cancer.
“Pancreatic cancer remains
the treatment of pancreatic estimated to be
elevated
in
among the most challenging can- pancreas cancer population and in specific newly diagnosed lung cancer cases and the
and small cell lung cancer,” said
159,260 deaths estimated to occur in the
cers in spite of recent treatment biomarker-selected subsets.”
Paul J. Hastings, OncoMed’s approximately 70
According to the American Cancer Society, United States in 2014. It tends to grow and
advances. The Phase 1b tarextumab
chairman and CEO. “OncoMed percent of
pancreatic cancer
data confirm safety and early signals there are approximately 46,000 new cases spread quickly and is typically not discovis enrolling patients in two ran- patients, and it is
of efficacy observed in earlier-stage of pancreatic cancer each year in the United ered until it has metastasized to other parts
domized Phase 2 clinical trials thought to be an
studies,” said Dr. Eileen O’Reilly, States. The majority of patients with pancre- of the body. In spite of a high sensitivity to
of tarextumab in pancreatic and indicator of poor
associate director of clinical atic cancer are diagnosed after their cancer chemotherapy and remission rates of up to
small cell lung cancer, and we prognosis and
research for Memorial Sloan Ketter- has spread locally and/or metastasized to dis- 80 percent following initial treatment, the
recently reported promising chemotherapy
ing Cancer Center and a principal tant organs. Rates of pancreatic cancer have median overall survival is less than one year
safety and early efficacy data resistance,” says
Dr. Jakob Dupont,
investigator of ALPINE. “Further been increasing over the past 10 years, and for patients with extensive stage disease.
from our Phase 1b studies in OncoMed’s chief
Tarextumab is part of OncoMed’s collaboexploration of tarextumab’s poten- it is now the fourth-leading cause of cancerthese indications.”
medical officer.
tial as a new treatment option for related deaths. The average life expectancy ration with GlaxoSmithKline, which has an
Tarextumab is a fully human
monoclonal antibody that targets the Notch2 pancreatic cancer patients is warranted and after the diagnosis of metastatic pancreatic option to obtain an exclusive license to tarextumab through completion of the proofand Notch3 receptors. Preclinical studies ongoing in the randomized Phase 2 portion cancer is less than one year.
Small cell lung cancer was estimated to of-concept Phase 2 trials. n
have suggested that tarextumab exhibits of the study. The trial will evaluate the additwo mechanisms of action: (1) by down- tion of tarextumab in a frontline untreated make up about 10 to 15 percent of the 224,210 EDITCONNECT: E031527
regulating Notch pathway signaling, tarextumab has anticancer stem cell activity and
(2) tarextumab affects pericytes, impacting
the stromal and tumor microenvironment.
Tarextumab is currently being studied in
two randomized Phase 2 clinical trials. The
Connect with the international network of
ALPINE study is assessing tarextumab with
“We are excited to receive
two separate orphan drug
designations for
tarextumab for the
treatment of pancreatic
and small cell lung cancer.
OncoMed is enrolling
patients in two randomized
Phase 2 clinical trials of
tarextumab in pancreatic
and small cell lung cancer,
and we recently reported
promising safety and early
efficacy data from our
Phase 1b studies in these
indications.”
Paul J. Hastings, chairman
and CEO of OncoMed
All of the luminaries of
the stem cell field in
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CREDIT: U.S FOOD AND DRUG ADMINISTRATION
FDA grants Orphan
Drug designations to
OncoMed’s tarextumab
for pancreatic and
small cell lung cancer
40 DDNEWS | | MARCH 2015
BUSINESS & GOVERNMENT POLICY
For more information, visit www.DDN-News.com
BETHSEDA, Md.—The U.S. National Institutes of Health (NIH) have awarded grants
of more than $28 million total aimed at
deciphering the language of how and when
genes are turned on and off. These awards
emanate from the recently launched Genomics of Gene Regulation (GGR) program of the
NIH’s National Human Genome Research
Institute (NHGRI).
“There is a growing realization that the
ways genes are regulated to work together
can be important for understanding disease,”
said Dr. Mike Pazin, a program director in
the Functional Analysis Program in NHGRI’s
Division of Genome Sciences. “The GGR program aims to develop new ways for understanding how the genes and switches in
the genome fit together as networks. Such
knowledge is important for defining the role
of genomic differences in human health and
disease.” With these new grants, researchers will
study gene networks and pathways in different systems in the body, such as skin, immune
cells and lungs. The resulting insights into
the mechanisms controlling gene expression may ultimately lead to new avenues for
developing treatments for diseases affected
by faulty gene regulation, such as cancer,
diabetes and Parkinson’s disease.
Over the past decade, numerous studies
have suggested that genomic regions outside of protein-coding regions harbor variants that play a role in disease. Such regions
likely contain gene-control elements that are
altered by these variants, which increase the
risk for a disease.
“Knowing the interconnections of these
regulatory elements is critical for understanding the genomic basis of disease,”
Pazin said. “We do not have a good way to
predict whether particular regulatory elements are turning genes off or activating
them, or whether these elements make genes
responsive to a condition, such as infection.
We expect these new projects will develop
better methods to answer these types of questions using genomic data.”
Recipients of the new GGR three-year
grants (pending available funds) are: Memorial Sloan Kettering Cancer Center, Duke
University, the University of Massachusetts
Medical School, Stanford University and University of California, Los Angeles. n
Regulatory roundup
H
ERE ARE just a few highlights
of recent regulatory activities worldwide, from patents
approved to designations
granted to drugs given the
green light for one indication or another.
MediciNova gain U.S., Japanese patents
LA JOLLA, Calif.— Biopharmaceutical
company MediciNova Inc. got word in early
February that it had received a Notice of
Allowance from the U.S. Patent and Trademark Office for a pending patent application
that covers MN-001 (tipelukast) and MN-002
(a major metabolite of MN-001) for the treatment of nonalcoholic steatohepatitis. The
patent maturing from this allowed patent
application is expected to expire no earlier
than December 2032. A few days earlier, the
company also noted that it had received a new
patent from the Japanese Patent Office covering MN-029 (denibulin) di-hydrochloride
that will expire no earlier than July 2032.
FDA grants Breakthrough Therapy
designation to Roche’s MPDL3280A
BASEL, Switzerland—Following a Breakthrough Therapy designation for MPDL3280A
from the U.S. Food and Drug Administration
(FDA) in bladder cancer in 2014, Roche has
gotten a second such designation for the
investigational anti-programmed deathligand 1 (anti-PDL1) cancer immunotherapy
for treatment of people with PD-L1-positive
non-small cell lung cancer whose disease has
progressed during or after platinum-based
chemotherapy (and appropriate targeted
therapy for those with an EGFR mutationpositive or ALK-positive tumor).
Symplmed announces FDA approval of
Prestalia for hypertension
CINCINNATI & BEND, Ore.— Jan. 26 saw
Symplmed Pharmaceuticals announce that
the FDA had approved Prestalia (perindopril
arginine and amlodipine) tablets, licensed
from French pharma Servier, for the treatment of hypertension. Prestalia, the first fixed-dose combination of these two medications, may be used in patients whose blood
pressure is not adequately controlled on
monotherapy. Prestalia may be used as initial
therapy if a patient is likely to need multiple
drugs to achieve their blood pressure goals.
ApoCell gains EU Orphan
Drug designation for
graft-versus-host disease
JERUSALEM— Enlivex Therapeutics
announced recently that the European
Medicines Agency had granted Orphan
Drug status to the company’s lead product
candidate, ApoCell, for the prevention of
graft-versus-host disease (GvHD). Previously,
ApoCell received the same designation from
the FDA. The company plans to initiate a
Phase 2b/3 trial of ApoCell in GvHD in 2015.
FDA approves Triferic for iron
replacement and maintenance of
hemoglobin in hemodialysis patients
WIXOM, Mich.—In January, Rockwell Medical
Inc., a biopharmaceutical company targeting
end-stage renal disease and chronic kidney
disease, noted that the FDA had approved its
drug Triferic for commercial sale as an iron
replacement product to maintain hemoglobin
in adult patients with hemodialysis dependent
chronic kidney disease.
“We are extremely pleased with the FDA
approval of Triferic. It is the first drug approved to replace ongoing iron losses and to
maintain hemoglobin levels in hemodialysis
patients,” stated Robert L. Chioini, founder,
chairman and CEO of Rockwell. “Triferic’s
unique ability to be delivered via dialysate
and to deliver iron without increasing iron
stores strengthens its potential to become the
market-leading iron therapy treatment for
hemodialysis patients.” n
CREDIT: U.S. NATIONAL INSTITUTES OF HEALTH
Deciphering the language of gene regulation
Five research institutions stand to get a combined $28 million-plus in grants as part of the
Genomics of Gene Regulation program of the National Human Genome Research Institute,
which is part of the National Institutes of Health (the clinical center of which is pictured here).
PATENT
CONTINUED FROM PAGE 36
all the different-sized molecules in the
mixture while giving heavier molecules a
weight-related bonus when doing so). The
trial court decided that the term meant the
peak average molecular weight, and thus
that the claim was sufficiently definite that
it was not invalid. The Federal Circuit construed the claim without regard to the trial
court’s determination and found the claim
invalid for indefiniteness.
The Supreme Court reversed, holding
that the Federal Circuit must give deference to trial court decisions related to “subsidiary” facts upon which the court bases its
legal construction of patent claims. No such
deference is required when the trial court
restricts it consideration to the “intrinsic”
evidence (the claim language, the specification and the written record before the Patent Office), but any factual determinations
by the trial court based on evidence outside that record (e.g., treatises, dictionaries,
expert testimony) must be given deference
by the appellate court and reversed only if
the reviewing court finds clear error (i.e.,
actual mistake) in the factual findings.
The Court’s asserted rationale was that
standards for review of patent claim construction practice should be consistent with
how other appellate courts review mixed
questions of law and fact like claim construction (specifically, construing deeds and contracts). This standard of review was based on
a trial court’s “greater opportunity to engage
its capabilities of assessing the credibility of
the witnesses and its capacity to immerse
itself in the technical minutiae attendant
upon construing claims in the first place.”
The decision settled a question in the law
that has bedeviled the Federal Circuit since
the Cybor decision, being criticized by the
patent bar, academics and even members
of that court; much of this dissent related
to the practice’s encouragement of every
patent decision (because they all involve
claim construction by the trial court) and
the relatively high frequency of reversal
because the Federal Circuit came to a different conclusion on the facts. However,
applying the Supreme Court’s mandated
standard raises the risk that U.S. patent practice will lose some of the harmonizing effect
that was the principal motivation for and
the primary benefit of having a specialized
appellate court for patents. This is because
matters of claim construction are often very
dependent on the types of “factual” evidence
for which the Federal Circuit must now give
deference. Parties in patent litigation can be
expected to try to make as much of the claim
construction process before the trial court as
possible dependent on expert testimony and
other “subsidiary” fact-finding, to reduce the
likelihood of having the trial court decision
overturned on appeal. It is also possible that
patentees (at least for patent applications
filed after Teva) will try to limit the opportunity for such fact-finding by providing
explicit definitions in their specifications.
For highly complex technologies including biotechnology and pharmaceutical patents, it is likely that trial court judges will
need expert or other testimony to understand the language of the claims even in
the face of such express definitions. Thus,
the Teva decision is likely to shift the center of patent claim construction towards
the trial courts and away from the Federal
Circuit. This can be expected to influence
both how patents for pharmaceuticals are
drafted, prosecuted and litigated in ways
that are in some ways predictable and in
others are beyond prediction. n
EDITCONNECT: E031526
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/.
For more information, visit www.DDN-News.com
HOSPIRA
CONTINUED FROM PAGE 1
According to Pfizer, the global marketplace value for generic sterile injectables is
estimated to be $70 billion in 2020, and the
marketplace for biosimilars is estimated to be
approximately $20 billion in 2020.
“The Pfizer-Hospira combination is an
excellent strategic fit, presenting a unique
opportunity to leverage the complementary
strengths of our robust portfolios and rich pipelines,” said F. Michael Ball, CEO of Hospira.
Despite having helped engineer the offer
from Pfizer, which is valued at nearly 40 percent more per share for Hospira’s stock than
it was worth just a day before the deal was
announced, early speculation from analysts
say Ball is not likely to stick around. “I would
be really shocked to see him stay on at Hospira,”
Michael Waterhouse, an analyst at Chicagobased Morningstar, told Crain’s Chicago Business.
And he may be very far from the only one
leaving, too, once the deal is done. Pfizer
anticipates the transaction will deliver $800
million in annual cost savings by 2018. Market-watchers seem to think that can only come
with layoffs, among them Ronny Gal, a senior
research analyst at Sanford Bernstein, who
told Crain’s, “I don’t see how they do that without firing [people]…Some of it will come from
their business, presumably, but I don’t see how
they would do that without taking out a lot of
the cost structure of Hospira.” Kevin Kedra, an
analyst at Gabelli & Co., agreed that “there will
obviously be some degree of layoffs.”
Pfizer dodged the question of the potential scale of layoffs at Hospira, which has
around 19,000 employees globally, when it
conducted its conference call with investors
after announcing the M&A deal. But Pfizer’s
Ian Read did say during the call, “We are very
well aware that Hospira has a lot of talented
individuals and have been very successful, as
our organization has been successful, so we
look to create a combined organization that
has the best talent from both organizations,”
which certainly seems to suggest a significant
number of pink slips are on the way.
“It remains to be seen what Pfizer will
do with its GEP business after the integration of Hospira. The Hospira deal will add
significant value to Pfizer’s GEP segment, a
vertical which has been rumored to be sold
or spun-off as a separate entity,” according to
Adam Dion, GlobalData’s healthcare industry analyst. “This somewhat mirrors Pfizer’s
strategic objective to focus on core growth
platforms in the branded drug market while
divesting its ancillary operations, similar to
when it carved out its Animal Health business (Zoetis) and brought it public. The
Zoetis initial public offering was preceded by
Pfizer selling its Nutrition business and Capsugel pill unit, mobilizing significant capital
for investment in its core growth areas. However, given Pfizer’s desire to retain its pharma
leadership and move into biosimilars, it may
decide against a split in favor of maintaining
a level of operational independence between
its innovative and mature portfolios.”
Dion also notes that while Hospira’s generic specialty injectables product line will be
seamlessly integrated into Pfizer’s GEP business, the newly acquired company’s biosimilar activities will also be of key importance
to Pfizer’s strategic objective.
“Hospira currently markets three biosimilars in Europe—Retacrit (erythropoietin zeta),
Nivestim (filgrastim) and Inflectra (infliximab), the first biosimilar monoclonal antibody
to be approved in Europe. Meanwhile, Hospira
BUSINESS & GOVERNMENT POLICY
“Hospira’s business aligns well with
our new commercial structure and is
an excellent strategic fit for our Global
Established Pharmaceutical (GEP)
business, which will benefit from a
significantly enhanced product
portfolio in growing markets.”
Ian Read, chairman and CEO of Pfizer
also has a number of biosimilars in its latestage pipeline, including trastuzumab, currently in Phase 3, which is being evaluated for
breast cancer. This is hugely complementary
to Pfizer’s own ongoing activities in biosimilar
development, with biosimilars of Herceptin, Rituxan and Remicade currently in the
pipeline,” Dion says.
Right after the announcement of the M&A
deal, Seamus Fernandez and Aneesh Kapur
of Leerink Partners wrote that “Compared
to recent pro-formas we have evaluated
(among them Pfizer/AstraZeneca, Pfizer/
Shire and Pfizer/Bristol-Myers Squibb),
Hospira is more accretive in the near term
and ought to drive a higher valuation on a
DCF [discounted cash flow] basis.”
Just a day before that, the two Leerink
analysts had also written positively about
Pfizer and hinted at M&A possibilities, noting, “Ibrance’s early approval and disclosed
$9,850/month pricing supports our expectations of a $3-billion to $5-billion market
opportunity for CDK4/6 inhibitors in firstline advanced ER+/HER2- breast cancer.
We expect brisk uptake with the potential
for Ibrance (palbo) to exceed our $150 million 2015 estimate … We continue to expect
Ibrance’s expansion into the recurrent disease
and early breast cancer setting, building up to
our $4 billion-plus forecasts in 2020. Despite
an important Ibrance readout in recurrent
breast cancer in 2015, we are more intrigued
by building strength across Pfizer’s mid-stage
vaccines, immunology and immuno-oncology
pipeline and/or accretive M&A.” n
EDITCONNECT: E031501
MARCH 2015 | | DDNEWS 41
EDGE
practice genomically enhanced medicine,
launched in late January a cloud-based
system for conducting patient-centered
translational research. Appistry CloudDx
Translational is said to meet a critical need
in clinical research centers: centralizing
and coordinating data, processes and
communication to leverage institutional
expertise and deliver high-quality results
to patients and the research community.
CloudDx Translational enables clinical
research centers engaged in the study of
human disease to build a personalized medicine framework for organizing research
activities. All project information is tied
to individual patients—including clinical
observations, research activities, reporting
of results and deposition of appropriate
findings into the public domain. CloudDx
Translational integrates the various tasks
needed to perform translational research,
provides expert systems to facilitate the
work of project team members and ensures
that valuable data and insights are searchable and shareable to inform hypothesis
generation and decision-making, while
holding patient identifiable information
secure in accordance with ethical practices
of human-subject research.
“CloudDx solutions have at their core
a keen understanding of the complex
workflows that must be managed and
facilitated to put patients at the center
of care, whether it be a research project
or a genomic test,” said Kevin Haar, CEO
of Appistry. “CloudDx Translational and
CloudDx Clinical are very different products, because they are designed to meet
the needs of different users. Yet they
share a connection to using the cloud to
minimize overhead and help institutions
gain the capabilities they need to deliver
value-added services based on genomics—what we call genomically enhanced
medicine.” n
CONTINUED FROM PAGE 38
ciate professor for the City of Hope Lung
Cancer and Thoracic Oncology Program.
“We look forward to evaluating Trovagene’s
molecular diagnostics for the monitoring
of circulating tumor DNA found in both
urine and blood, with the goal of delivering highly personalized cancer treatment
to improve patient outcomes.”
The clinical study is expected to enroll 75
patients with lung cancer. Primary objectives of the study include evaluating concordance between urinary circulating tumor
DNA (ctDNA), blood ctDNA and tumor
tissue for determining EGFR mutational
status. Additionally, the study investigators
will evaluate the quantitative and qualitative
performance of longitudinal EGFR mutation
monitoring using both urine and blood specimens, as they relate to response to therapy
over time. Exploratory objectives include
evaluating the feasibility of identifying the
TKI-resistant mutation, T790M, in urinary
and blood ctDNA at the time of progression.
“Enabling physicians to detect the
emergence of problematic mutations in
real-time is a key benefit of our Precision
Cancer Monitoring platform, and one
such mutation is EGFR T790M, which
drives treatment resistance in non-small
cell lung cancer patients,” said Dr. Mark
Erlander, chief scientific officer of Trovagene. “This is an important part of our
strategy to realize the full potential of our
platform, as we partner with major cancer
treatment centers in the U.S. to obtain
clinical utility data and to integrate our
technology into clinical practice.”
Appistry launches cloud-based
system for patient-centered
translational research
MOUNTAIN VIEW, Calif.—Appistry Inc.,
a provider of tools, software and services
that enable healthcare institutions to
EDITCONNECT: E031528
APRIL 18-22, 2015
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42 DDNEWS | | MARCH 2015
LATE-BREAKING NEWS
For more information, visit www.DDN-News.com
Late-Breaking News
Three M&A deals combine for about
$16 billion in dealmaking in February
HREE PARTICULARLY NOTABLE merger and acquisition (M&A) deals came
together during the late stages of producing this issue. We’ve covered them
in more detail online at our www.ddn-news.com
website in the Daily News section, but here are
some highlights for you.
Valeant to acquire Salix
Pharmaceuticals in $14.5 billion deal
LAVAL, Quebec—While it isn’t anywhere near what
Valeant Pharmaceuticals International Inc. tried
to buy Allergan Inc. for last year ($54 billion in an
unsolicited and ultimately failed takeover bid), Valeant
just made its biggest acquisition deal ever this
month, announcing a $158-per-share offer for Salix
Pharmaceuticals, a major player in the growing U.S.
gastrointestinal (GI) market, that has been accepted
by the boards of both companies. That’s an all-cash
deal for $10.1 billion, plus the assumption of more
than $4 billion in debt, for a total enterprise value of
$14.5 billion, the two companies announced Feb. 22.
That clearly trumps Valeant’s acquisition of eyecare company Bausch & Lomb in 2013 for $8.7 billion.
Salix is best known for its irritable bowel syndrome
drug Xifaxan. However, the company’s portfolio of
22 total products also includes such prescription
brands as Uceris, Relistor and Apriso, “as well
as a strong near-term pipeline of innovative, new
assets,” according to Valeant.
“Salix’s market-leading gastrointestinal franchise
is an ideal strategic fit for Valeant’s diversified
portfolio of specialty products,” according to J.
Michael Pearson, Valeant’s chairman and CEO. “The
growing GI market has attractive fundamentals, and
Salix has a portfolio of terrific products that are
outpacing the market in terms of volume growth
and a promising near-term pipeline of innovative
products. With strong brand recognition among
specialist GI prescribers, a highly rated specialty
sales force and a significant product and commercial
presence across the undertreated and underserved
gastrointestinal market, this acquisition offers a
compelling opportunity for Valeant to create a strong
platform for growth and business development.”
The combination is expected to yield more than
$500 million in annual cost savings from the cost base
of the combined company. Synergies are expected to
be achieved within six months of close, primarily from
reductions in corporate overhead and research and
development rationalization, with the cost to achieve
these synergies said to be approximately 65 percent.
“We are pleased to have reached an agreement
with Valeant, which is a logical partner and, importantly, creates immediate value for our shareholders.
Combining Salix’s leading market position in gastroenterology with Valeant’s scale and resources
will create a stronger and more diverse business
committed to providing better health solutions to
healthcare providers and their patients,” said Thomas
W. D’Alonzo, chairman and acting CEO of Salix.
On Nov. 6, 2014, Salix reported five- to nine-month
wholesaler inventory levels for its top four products. Valeant says it has conducted extensive due
diligence on Salix’s standalone wholesaler inven-
tory levels, standalone inventory work-down plan
and associated potential litigation and regulatory
exposure. Valeant expects to work down wholesale
inventory and plans to target two months or less of
wholesale inventory by the end of this year. The net
impact of the excess inventory on 2015 revenues is
expected to be greater than $500 million.
The all-cash offer for all of the outstanding shares
of Salix common stock will be financed through a
combination of bank debt and bonds. As a result of
the need to draw down inventories, Valeant says
that earnings before interest, taxes, depreciation
and amortization will be artificially low in 2014 and
2015, resulting in the initial net leverage ratio of
approximately 5.6. Valeant says it is committed
to reducing its net leverage ratio to be below 4.0
by the second half of 2016. As a result of the plan
to reduce wholesaler inventory levels in 2015, the
transaction is expected to be modestly accretive
to 2015 cash earnings per share, but more than
20-percent accretive to 2016 cash earnings per share.
For the full version of this story online, search for
Editconnect code E02251502 on our website. Also,
we will have additional coverage of this deal in
our April issue of DDNews, examining some of the
implications of the acquisition and its market impact.
Immediately following a deal to acquire NPS Pharma for $5.2 billion, announced January of this
year, Shire has now acquired Meritage Pharma, a developer of drugs for gastrointestinal and
rare diseases, for $70 million up front and as much as $175 million in milestone fees.
Bristol-Myers Squibb to pay up to
$1.25 billion for Flexus
CREDIT: NYSE
T
BY JEFFREY BOULEY & KELSEY KAUSTINEN
NEW YORK & SAN CARLOS, Calif.—Bristol-Myers Squibb
Co. and Flexus Biosciences Inc. have struck a
definitive agreement by which Bristol-Myers Squibb
will acquire all of Flexus’ outstanding capital stock
in a deal with a potential total consideration of
$1.25 billion, which includes $800 million up front
and up to $450 million in development milestone
payments. Both companies’ boards of directors
have approved the transaction, as have Flexus’
stockholders, and the deal was expected to close
in the first quarter of this year.
“Bristol-Myers Squibb is a recognized leader in
the cancer immunotherapy field, and we are delighted with the opportunity to have their organization
advance the development of our potentially best-inclass IDO/TDO inhibitors and to bring more innovative cancer immunotherapies to patients,” said Dr.
Terry Rosen, CEO of Flexus. “With the consummation
of this acquisition, we will continue to advance our
oncology and immuno-oncology pipeline of Agents
for Reversal of Tumor Immunosuppression in the
newly created spin-off, with the strong support of
our committed group of investors.”
IDO and TDO are enzymes expressed by a number
of tumor cells and cells in the tumor microenvironment, and these enzymes suppress T cell function
through the production of kynurenine, a potent
immunosuppressive factor that prevents the immune
system from identifying and destroying the tumors.
IDO/TDO inhibitors reduce the production of kynurenine, freeing up the immune system to better
attack tumors. With this acquisition, Bristol-Myers
Squibb gains full rights to F001287, Flexus’ lead
preclinical small-molecule IDO1-inhibitor, which
is aiming for Investigational New Drug filing in the
second half of this year. Bristol-Myers Squibb also
gets Flexus’ IDO/TDO discovery program, which
Representatives of Valeant ring in the closing bell for the New York Stock Exchange on Oct. 10,
2013, on World Sight Day. In May of that year, Valeant’s acquisition of Bausch and Lomb at
nearly $8.6 billion was the company’s largest acquisition to date. That has been eclipsed now
by the $14.5-billion deal to acquire Salix.
includes the company’s IDO-selective, IDO/TDO
dual and TDO-selective compound libraries.
Per the terms of the agreement, a newly formed
entity established by Flexus’ current shareholders
will retain all non-IDO/TDO Flexus assets, including
those related to Flexus’ Phase 1 FLT3 and CDK4/6
inhibitor, its earlier-stage small-molecule Treg
cancer immunotherapy programs and its current
personnel and facilities.
“Bristol-Myers Squibb is committed to leading
scientific advances in immuno-oncology, and our
acquisition of Flexus will expand our innovative
pipeline with an important approach to enhancing
immune responses in cancer,” said Francis Cuss,
MB BChir, FRCP, executive vice president and
chief scientific officer at Bristol-Myers Squibb.
“With the addition of a potentially best-in-class
IDO1 inhibitor and the broad IDO/TDO programs,
Bristol-Myers Squibb will accelerate its ability to
explore numerous immunotherapeutic approaches
across tumor types, including combinations with
our biologic checkpoint and co-stimulatory agents
that target different and complementary pathways.”
For the full version of this story, which also
addresses a collaboration made at the same time
as the M&A deal, search for Editconnect code
E02241501 on our website.
Shire to pay up to $245 million
in Meritage acquisition
LEXINGTON, Mass. & SAN DIEGO—Shire
plc has
announced the acquisition of privately held Meritage
Pharma Inc., which specializes in developing prescription products for the treatment of gastrointestinal and atopic diseases, for $70 million up front
and as much as $175 million in milestone fees.
With this deal, Shire gains the global rights to Oral
Budesonide Suspension (OBS), Meritage’s Phase
3-ready compound for the treatment of adolescents
and adults with eosinophilic esophagitis (EoE), a
rare, chronic inflammatory gastrointestinal disease.
OBS has received Orphan Drug designation from
the U.S. Food and Drug Administration for the
treatment of patients with EoE.
Shire obtained the rights to acquire Meritage
last year, in connection with its acquisition of
ViroPharma. Shire closed the deal with ViroPharma
in early 2014, announcing on Jan. 24 that it had
successfully completed its tender offer for all
outstanding shares of ViroPharma stock. Shire does
not expect the Meritage transaction to affect its
previously published earnings guidance for the year.
“Shire’s pipeline and strategic focus on rare
diseases is further strengthened with the acquisition of Meritage, which also complements our
strong GI capabilities. Adding this Phase 3-ready
compound to our late-stage portfolio will allow us
to leverage our expertise to further develop this
important therapy that, if approved, will give hope
to patients living with eosinophilic esophagitis,” Dr.
Philip J. Vickers, head of research and development
at Shire, commented in a statement.
For the full version of this story, search for
Editconnect code E02261501 on our website. n
For more information, visit www.DDN-News.com
AWARDS & HONORS
MARCH 2015 | | DDNEWS 43
Awards & Honors
WITec’s RISE microscope wins Prism Award 2015
SAN FRANCISCO—WITec
and Tescan have been
recognized with a 2015 Photonics Prism Award
for their RISE microscope. The award is given for
top innovations in the field of photonics, granted
by Photonics Media and sponsored by the international Society for Optics and Photonics (SPIE).
The winners were chosen from more than 130
applicants and were announced during SPIE
Photonics West on Feb. 11.
RISE microscopy is a novel correlative
microscopy technique that combines confocal
Raman imaging and scanning electron (hence
the acronym RISE) microscopy within one integrated microscope system. This combination is
said to enable the most comprehensive sample
characterization, as electron microscopy is an
excellent technique for visualizing sample surface
structures in the nanometer range and confocal
Raman imaging is an established spectroscopic
method used for the detection of the chemical
and molecular components of a sample.
It can also generate 2D- and 3D-images and
depth profiles to visualize the distribution of the
molecular compounds within a sample.
“The RISE Microscope is another striking
example of WITec’s enormous innovative strength.
We are proud to once again receive a Prism
Award, the second after being recognized in 2011
for WITec’s TrueSurface microscopy technology,”
said Dr. Olaf Hollricher, WITec’s managing director
of research and development.
The microscope’s development was a joint
effort of WITec and Tescan within the UNIVSem
project, funded by the European Union. n
Dr. Klaus Weishaupt (left), WITec managing director of marketing and sales, and the WITec/
Tescan team accept the Prism Award 2015. From left to right of Weishaupt are Jeff Streger of
Tescan USA Inc., Radomír Koprˇiva of Tescan Orsay Holding and Steve Rapp of WITec.
EMD Millipore, the Life Science division of Merck KGaA (pictured here), recently announced
NGM Biopharmaceuticals Inc. as the recipient of its 2014 Emerging Biotech Grant Program.
From left to right are Drs. Yutaka Takahasi, Alain Fischer and Theodore Friedmann, winners of
the 2015 Japan Prize.
EMD Millipore announces Emerging
Biotech Grant Program winner
Horizon Discovery CEO wins
Entrepreneur of the Year award
BILLERICA, Mass.—EMD Millipore, the life-sciences
division of Merck KGaA in Darmstadt, Germany,
announced in January that NGM Biopharmaceuticals
Inc. is the recipient of its 2014 Emerging Biotech
Grant Program.
Committed to helping advance lifesaving drugs
to market, EMD Millipore hosted its first emerging
biotech grant program, in which the winner receives
products and services from EMD Millipore to help
develop their molecule. More than 300 entries
were accepted from Sept. 3 through Nov. 30, 2014.
The winning entry was selected based on objective criteria of equal weight: the scientific and
societal merit of the therapy being developed
and the process challenges and expertise gaps
associated with the development of the therapy.
NGM Biopharmaceuticals is an innovative drug
discovery company located in San Francisco that is
engaged in identifying and developing biologics for
the treatment of cardiometabolic conditions, bile
acid-related disease and potentially other diseases
resulting from manifestations of cardiometabolic
abnormalities and metabolic-related cancers.
2015 Japan Prize honors pair of gene
therapy pioneers
TOKYO—The
Japan Prize Foundation recently
announced that it has selected three distinguished
scientists as winners of the Japan Prize, now in its
31st year, which is awarded annually to scientists
and researchers in two categories who, regard-
less of nationality, made substantial contributions
to their fields and advancement of science and
technology as well as serving the cause of peace
and prosperity of mankind. This year’s winners
were Drs. Theodore Friedmann, Alain Fischer and
Yutaka Takahasi.
Friedmann and Fischer were honored in the field
of Medical Science and Medicinal Science as the
world’s first researchers to propose and clinically
prove a gene therapy concept.
Friedmann, currently professor of pediatrics at
the medical school of the University of California,
San Diego, proposed the concept of gene therapy
in the 1970s and pioneered the early phase of basic
research in the field. Regarded internationally as
the “father of gene therapy,” he has also been at
the vanguard of ethical issues surrounding this
field as an opinion leader for the past 40 years.
For his part, Fischer used hematopoietic stem cell
gene therapy to treat children with a fatal genetic
disorder called X-linked severe combined immunodeficiency and clinically demonstrated efficacy
of gene therapy with dramatic effectiveness for
the first time. Fischer has been director of Institut
Imagine in Paris, a leading research institute on
genetic diseases, since 2007 and a professor at
Collège de France since 2014.
Takahasi, a professor emeritus of the University
of Tokyo, won in the field of Resources, Energy
and Social Infrastructure for his contribution to
development of an innovative concept on river
basin management and reduction of water-related
disasters.
CAMBRIDGE, U.K.—Horizon
Discovery Group plc
an international life-sciences company supplying research tools and services to organizations
engaged in genomics research and the development
of personalized medicines, announced in January
that the company’s CEO, Dr. Darrin Disley, had been
awarded Entrepreneur of the Year at the Quoted
Company Awards 2015 in London.
Disley has overseen a transformational year for
Horizon, during which the company transitioned from
a private life-sciences business employing 85 staff
on a single 18,000-square-foot site in Cambridge to
a publicly listed international life-sciences group
employing 200 staff across over 85,000 square feet
of facilities located in the United Kingdom, Austria
and the United States.
Under his leadership, Horizon listed on AIM market of the London Stock Exchange in March 2014,
when the company was able to raise £68.6 million,
nearly three times the initial target for its initial public
offering. Since then, Disley has driven Horizon’s
growth through a series of targeted acquisitions
into high-value areas of the personalized medicines
space: CombinatoRx based in Cambridge, Mass.;
SAGE Labs based in St. Louis and Boyertown, Penn.;
and most recently, Haplogen Genomics located in
Vienna, Austria. He has also expanded the suite
of products and services available to Horizon’s
customers, bolstered the company’s intellectual
property position and delivered high-value contracts
with leading life-sciences companies.
“To be recognized as an innovator and leader
by my peers is a tremendous honor,” said Disley.
“This has been an incredibly dynamic and exciting
year for me and my colleagues at Horizon, and it
is a testament to them that we have been able to
be as successful as we have and to be as well
positioned as we are for the future.”
Prosensa wins Scrip Biotech
Company of the Year award
LEIDEN, The Netherlands—Late
last year, Prosensa
Holding N.V., a biopharmaceutical company focusing on RNA-modulating therapeutics for rare diseases with a high unmet medical need, won the
Scrip Biotech Company of the Year award for 2014,
announced in London.
The Scrip Awards provide an opportunity to
acknowledge and applaud the highest achievers
across the biotechnology and pharmaceutical
industry, recognizing both corporate and individual
accomplishments. The award for Biotech Company
of the Year is given to the company which has demonstrated the greatest achievements for the year.
Hans Schikan, CEO of Prosensa, said, “Winning
Scrip’s Biotech Company of the Year award is a great
honor and a testament to the dedication and hard
work of the Prosensa team. Our drive to succeed is
fueled by patients and their families, who continue
to inspire us to make innovative therapies available
as quickly and efficiently as possible.”
The other five finalists were Ablynx, Horizon
Discovery, Isis Pharmaceuticals, Mesoblast and
Silence Therapeutics. n
PRODUCTS & SERVICES
44 DDNEWS | | MARCH 2015
Thermo Scientific Q
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Fisher
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ATCC
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Seahorse
Bioscience
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ReproCELL
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Crown Bioscience Inc.
Crown Bioscience now offers in-vivograde isotype control antibodies
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•Suitable for in-vivo studies and
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[email protected]
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‘Think Possible’ with BioTek
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PRODUCTS & SERVICES
For more information, visit www.DDN-News.com
MARCH 2015 | | DDNEWS 45
ADVERTISER ’S INDEX
The Simplicity-888 Controlled
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OncoSignature
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PLAS-LABS Inc.
Horizon Discovery
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Eppendorf announces new
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AACR Conference.......................................................41
Affymetrix.....................................................................29
ATCC..............................................................................15
Bio-Rad Laboratories, Inc.........................................48
Biosearch Technologies, Inc...................................47
BioTek Instruments, Inc............................................31
Cell Signaling Technology, Inc................................23
ChemBridge Corporation..........................................30
Cisbio US, Inc................................................................ 7
Crown Bioscience, Inc..............................................21
Drummond Scientific Company................................. 9
eBioscience .................................................................. 3
Eppendorf North America........................................... 5
Horizon Discovery Ltd................................................27
INDIGO Biosciences..................................................20
ISSCR Conference......................................................39
Kiyatec, Inc..................................................................18
Kuraray Co. Ltd............................................................32
OriGene Technologies, Inc................................ Cover
PerkinElmer.............................................................2, 19
Plas-Labs,Inc...............................................................37
R&D Systems, Inc. .....................................................13
Rockland Immunochemicals, Inc...........................16
Seahorse Bioscience................................................25
Stemgent, Inc...............................................................35
Thermo Fisher Scientific............................................. 8
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People & Promotions
Vaccinogen makes significant moves in early 2015
FREDERICK, Md.—A trio of news items
marked the early part of this year for
Vaccinogen Inc., a cancer vaccine company
that is clinically testing OncoVAX, a treatment designed to prevent the recurrence
of colon cancer and potentially other solid
tumors—two of them related to people
being placed in important positions and
one of them arguably attributable to all
of the people involved with the company.
On Jan. 12 came the news that Dr. Peter
Morsing, a 20-year pharmaceutical industry
veteran whose most recent jobs were roles of
increasing responsibility with AstraZeneca, had
joined the company as head of business development. Morsing says of his new job, “I am eager
to apply my decades of experience in licensing and pharmaceutical development to help
the Vaccinogen team establish a first-in-class
monoclonal antibody library using immune cells
collected during the upcoming OncoVAX clinical study. This will be a significant milestone for
advancing personalized medicine, and we hope
to bring more optimal cancer therapies to the
broader patient population by partnering with leading pharmaceutical and genomics companies.”
Just under a month later, the company
announced that Håkan Edström, a healthcare
industry veteran with more than 40 years of
experience, had been elected to the company’s
board of directors and would chair the company’s
Compensation Committee as well as serve on the
Audit Committee. Edstrom was recently named
CEO of MannKind Corp., following his 14-year
tenure as president and chief operating officer of
the company. He previously held leadership roles
Sanofi
SNBL USA Ltd.
Olivier Brandicourt, M.D.
Tina Rogers, Ph.D.
Chief Executive Officer
Director of Safety Assessment
Mark Page
PARIS—On Feb.
19, Sanofi appointed Dr. Olivier
Brandicourt as
CEO, with the plan
for him to begin
his duties officially
on April 2. He has
28 years of global
experience in the
pharmaceutical
industry, most
recently as chairman of the board
of management of
Bayer HealthCare AG and member of the executive
council of Bayer AG. Previously, Brandicourt held
numerous positions of increasing responsibility within
major global pharmaceutical groups, such as ParkeDavis/Warner-Lambert and Pfizer. Notably, Brandicourt
served as a member of Pfizer’s global executive leadership team from 2010 to 2013. As the head of various key
healthcare divisions, he has a broad range of expertise
and knowledge of the pharmaceutical industry and has
led the launch of numerous new medicines and the
completion of strategic acquisitions and integrations.
E V E R E T T,
Wash.—On Feb.
12, SNBL USA
announced the
appointment of Dr.
Tina Rogers as the
director of safety
assessment. In
this position, she
will manage dayto-day operations
of the department
to ensure continued operational
and scientific
excellence and help direct strategic plans, objectives and policies to support sponsors with the
highest level of compliance and efficiency. Over
her 20 years of industry experience, Rogers has
provided preclinical drug development services to
biopharma, the U.S. National Institutes of Health
and the U.S. Department of Defense. SNBL USA
offers programs ranging from regulatory toxicology to customized study designs in multiple drug
classes (biologics, small molecules, oligonucleotides and vaccines).
Chief Financial Officer
PETACH TIKVA, Israel—Macrocure, a clinicalstage biopharmaceutical company focused on
developing a novel therapeutic platform to address
chronic and hard-to-heal wounds, announced
recently that Mark Page would join the company
as chief financial officer, effective Feb 10, 2015.
Page joins Macrocure from Credit Suisse’s Global
Healthcare Investment Banking Group, where he
led the firm’s medical device franchise since 2010,
adding to his healthcare-dedicated corporate
finance and strategic background that spans
20 years of experience.
Macrocure Ltd.
SCYNEXIS Inc.
Marco Taglietti, M.D.
Chief Executive Officer
RESEARCH TRIANGLE PARK, N.C.— In February, drug
discovery and development company SCYNEXIS
named Dr. Marco Taglietti as CEO, effective April
1. Taglietti, a member of the SCYNEXIS board of
directors, will succeed Dr. Yves Ribeill, who will
remain the company’s president and continue
to serve on the SCYNEXIS board. Taglietti was
appointed to the SCYNEXIS board in December
2014. He previously served as executive vice
with Bausch & Lomb, serving as vice president and
president of the Global Surgical Division and senior
corporate vice president of the Americas Region.
In between those two pieces of news came
word from Vaccinogen on the closing of the second $10-million tranche of a $80-million financing
announced August 2014. This second tranche
brings the total amount closed to $20 million of the
$80 million committed at $5.50 per share or unit.
The capital will be used to fund further company
expansion and ACTIVE, a confirmatory Phase 3b
study of OncoVAX.
president of research and development and chief
medical officer of Forest Laboratories Inc. and
also as president of the Forest Research Institute
until the company was acquired by Actavis plc.
Prior to joining Forest Labs, Taglietti was senior
vice president and head of global research and
development at Stiefel Laboratories Inc. In an
unrelated matter, Dr. Carole Sable, the chief
medical officer at SCYNEXIS, stepped down,
effective Feb. 20.
Rexahn Pharmaceuticals Inc.
Ely Benaim, M.D.
Chief Medical Officer
ROCKVILLE, Md.—Rexahn Pharmaceuticals, a
clinical-stage biopharmaceutical company
focused on therapeutics for the treatment of
cancer, recently announced the appointment
of Dr. Ely Benaim, as chief medical officer. In
this role, Benaim will be responsible for leading Rexahn’s clinical development programs
and providing strategic and clinical guidance
for the company. Benaim has more than 25
years of experience in healthcare, including
15 years of clinical research experience in
academia, government and pharmaceutical
industry, as well as extensive experience in
global regulatory affairs.
Q&A: Nissim Mashiach
Q&A of Macrocure
46 DDNEWS | | MARCH 2015
For more information, visit www.DDN-News.com
Macrocure and the wound-care market
C
BY LLOYD DUNLAP
HRONIC AND HARD-TO-HEAL wounds are a serious
and growing $5.3-billion problem affecting more
than 2 million people in the United States, European Union and Japan. Common results of chronic wounds include comorbidities and mortality,
lengthened hospital stays and a significant increase in the cost
of care, all of which have a negative impact on the quality of life
of both the patients and caregivers. DDNews recently explored
possible remedies with Nissim Mashiach, president and CEO
of the Israeli company Macrocure Ltd.
DDNews: Nissim, could you explain to our readers
your company’s track record in regenerative
medicine, wound care and the development and
commercialization of biologics?
Nissim Mashiach: Founded in 2008, Macro-
cure is focused on developing a novel therapeutic platform to address chronic and hardto-heal wounds, such as diabetic foot ulcers
(DFUs) and venous leg ulcers (VLUs). My
company’s lead product candidate, CureXcell, is a monthly injectable of living, human,
activated white blood cells. More than 5,000
patients have been treated in Israel to date,
where it has been approved for commercialization for the past 17 years. We are currently
in two pivotal double-blind Phase 3 clinical
trials in the U.S., with data expected in the
second half of 2015. My management team
has a wide range of experience in developing
and commercializing biologics. For example,
I have worked at Ethicon (Johnson & Johnson) and Omrix Biopharmaceuticals.
DDNews: How does your product’s contact with
the injured person’s wound bed trigger a body’s
endogenous healing process?
The healing process can be triggered by the injection of a mixture of activated
white blood cells obtained from young healthy
donor blood into the wound bed. The mixture
can replenish the imbalanced inflammatory
environment in the nonhealing wound with
functionally active immune cells that release
the necessary growth factors and are capable
of phagocytosis of bacteria and dead cells in
the wound bed. Recent findings from our
mechanism of action study confirmed that
CureXcell has over 55 growth factors and cytokines that participate in all stages of wound
healing. The amplification of the cytokines
and growth factors found in CureXcell assures
a very high concentration of these activated
Mashiach:
growth factors, which can explain the high
closure rate our product has demonstrated
versus standard of care in our previous clinical studies. By recreating the natural environment for wound healing, the appropriate cell
activities and factor secretions are maintained
as required during wound healing.
DDNews: Will CureXcell have applications
beyond chronic and hard-to-heal wounds such as
DFUs and VLUs?
Mashiach: Yes, CureXcell has potential mar-
ket applications in a wider range of regenerative medicine applications, including
aesthetic surgery, orthopedic surgery and
reconstructive surgery. One of the reasons
why we are doing robust clinical studies is
that we see CureXcell as a platform technology that may be applicable in many indications beyond wound healing.
DDNews: Would you explain to our readers the
important commercial potential of your company
and its products?
Chronic, hard-to-heal wounds
represent one of the largest, fastest-growing
segments of the wound-care market. The
worldwide advanced wound-care market
has existing sales of approximately $5.3 billion; there are approximately 800,000 new
DFU patients and approximately 1,300,000
new VLU patients each year in the U.S., EU
and Japan. Twenty-five percent of diabetes
patients will develop a foot ulcer; currently,
15 percent of hard-to-heal wounds result
in amputations. In fact, 80 percent of all
amputations in the U.S. are the result of nonhealing DFUs. Overall, the problem places
a $25-billion burden on the U.S. healthcare
system, which we believe we can help alleviate. In addition to this high unmet medical
need, there is an existing desire on the part
of physicians for alternate treatment options
Mashiach:
The amplification of the cytokines and growth factors
found in CureXcell assures a very high concentration of
these activated growth factors, which can explain the
high closure rate our product has demonstrated versus
standard of care in our previous clinical studies. By
recreating the natural environment for wound healing,
the appropriate cell activities and factor secretions are
maintained as required during wound healing.
Macrocure’s lead product is CureXcell, a cell-based therapy for hard-to-heal wounds that is
designed to restore the wound-healing process. It is currently only available for sale in Israel.
that are backed by strong clinical data and
favorable reimbursement. We believe that
CureXcell can address these unmet medical
needs and become an attractive solution for
physicians and patients.
data in the second half of 2015, file our
BLA in the second half of 2016 and obtain
approval in late 2017). We are seeking a
broad-label indication for CureXcell for all
wounds below the knee.
DDNews: Please explain the Macrocure process,
i.e., how it functions to heal wounds.
DDNews: What have been the results of clinical
studies thus far?
Mashiach: CureXcell is an injectable suspension of living white blood cells, including
macrophages, neutrophils and lymphocytes,
which are crucial to initiating, promoting and
completing the process of cellular regeneration and wound healing. Macrocure activates
the white blood cells via its proprietary hypoosmotic shock cell activation technology, a
process that changes the concentration and
pH of the suspension surrounding the cells.
Once activated, these cells undergo a change
in gene expression that results in an increase
in the cells’ secretion of numerous growth
factors and other biochemical factors.
A physician draws CureXcell from its sterile package using a standard syringe for injection into a patient’s wound. A direct application into the wound bed is a major advantage,
in that it allows the treatment to bypass the
biofilm and contaminated environment and
promote healing from the inside out. And as
a major boon to patients, the therapy involves
only one injection per month.
Mashiach: An Israeli clinical trial harnessing
DDNews: What are the regulatory hurdles you
may still face in the U.S. to obtain FDA approval
for this unique product?
Mashiach: FDA approval is contingent upon
meeting the DFU and VLU clinical trial endpoints (we expect to report full and interim
CureXcell has shown that after only approximately three injections directly into the
wound bed, there was a 64-percent closure
rate in DFU and over 80 percent in VLU. The
current clinical trials in the U.S. are designed
similarly to the Israeli trial in terms of inclusion/exclusion criteria. The trial is enrolling
the worst of the worst and includes patients
with low ABI and infection, and can include
patients post-amputation. n
EDITCONNECT: E031530
Nissim Mashiach has served as president and
CEO of Macrocure Ltd. since June 2012. Before
joining Macrocure, he served as general
manager at Ethicon, a Johnson & Johnson
company, from 2009 to 2012. Prior to that,
he served as president and CEO at Omrix
Biopharmaceuticals Inc., a company acquired
by Johnson & Johnson in 2008. Prior to Omrix,
Mashiach held various leadership positions at
several pharmaceutical companies. He holds
an MBA from the University of Manchester
in England, a master of pharmaceutical
science degree from the Hebrew University in
Jerusalem and a bachelor’s degree in chemical
engineering from the Technion-Israel Institute
of Technology in Haifa, Israel.
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