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PHARMA, BIOTECH & LIFE SCIENCE
RESEARCH & DEVELOPMENT
14
PRECLINICAL18
CLINICAL TRIALS
27
DIAGNOSTICS32
CONTRACT SERVICES
36
BUSINESS & GOVERNMENT POLICY
40
TOOLS & TECHNOLOGY
Strategically going digital...................................................14
Identification key to reproducibility..................................14
Looking ahead with PepSee..............................................15
Rheonix scores ‘positive’ with fast HIV test...................32
On the cutting edge.............................................................42
MARKET NEWS
3
EDITORIAL/COMMENTARY10
AWARDS & HONORS
44
PRODUCTS & SERVICES
45
LATE-BREAKING NEWS
46
SHOW PREVIEW:
Stem cells
in San Francisco
22
ISSCR 2016 Annual Meeting
comes to Bay Area in June
Biggest pharma combo becomes biggest bust
Rule changes by Treasury
Department mean trouble
for any U.S. companies
attempting inversion deals
in near term
BY JEFFREY BOULEY
NEW YORK & DUBLIN—Whether or not it
was the intent of the U.S. Department of
Treasury to scuttle the intended merger
plans between Pfizer Inc. and Allergan plc
with new rules about inversion deals—and,
let’s be honest, that was likely a big goal of
the Treasury Department—the deal is indeed
now a dead one. It could also mean the death
of hopes for other companies who want to
do inversions, at least for some time until
enterprising folks find the right loopholes.
We already reported the fact of the “Pfizergan” demise in our online article “Pfizer ends
plans to merge with Allergan” (which you can
find at www.ddn-news.com by searching for
the code E04131601), noting that, first off,
Pfizer and Allergan had planned to become
the biggest phama of them all in a $160-billion merger and acquisition (M&A) deal that
would, in part, have allowed U.S.-based Pfizer to reduce its tax burden by re-domiciling
in Ireland. Instead, Pfizer ultimately called
A new PATH for
eliminating
tropical diseases
PATH, SD/Alere
announce commercial
availability of diagnostic
tools for two neglected
tropical diseases
BY KELSEY KAUSTINEN
SEATTLE & SEOUL—Two new rapid diag-
nostic tools are now commercially available for lymphatic filariasis (LF) and
onchocerciasis, both of which are neglected tropical diseases (NTDs). PATH and
Standard Diagnostics (SD)/Alere partnered to make these tests available.
“We are pleased to have developed two
more rapid tests with PATH,” Byung-Ki
Cho, vice president of Asia Pacific operations and R&D at SD/Alere, remarked in
a statement. “The collaboration between
SD/Alere and PATH is designed to help
PATH CONTINUED ON PAGE 35
05.16
Among the neglected tropical diseases in
the crosshairs of PATH and Standard
Diagnostics/Alere are lymphatic filariasis,
spread by mosquitoes, and onchocerciasis
(river blindness), which is caused by a
parasitic worm transmitted to humans
through the bite of the blackfly.
CREDIT: ALLERGAN
DISCOVERY6
PUBLISHED SINCE 2005
Although Allergan had apparently been as eager as Pfizer to make a merger happen, it began
making new acquisition deals for itself almost immediately after the deal between it and Pfizer
was scuttled. Pictured here is an Allergan R&D site in California.
off the deal and gave Allergan $150 million
to help pay for the Irish company’s expenses
and trouble.
The second big thing we noted in that
article was that the Treasury Department
had twice made rule changes for M&As that
failed to dissuade Pfizer and Allergan and
then, finally, on April 4, the Treasury Department and the U.S. Internal Revenue Service
managed to spur Pfizer to kill the M&A plans
when they issued temporary and proposed
regulations to further reduce the benefits of
and limit the number of corporate tax inversions, in part by addressing what is called
earnings stripping.
As U.S. Treasury Secretary Jacob J. Lew
said in the April 4 news release about those
PFIZERGAN CONTINUED ON PAGE 43
Insulin with the quickness
Adocia and Lilly
announce positive Phase
1b results for ultra-rapid
BioChaperone Lispro
BY JEFFREY BOULEY
LYON, France & INDIANAPOLIS—Adocia and
Eli Lilly and Co. announced in late April positive top-line results from a Phase 1b clinical
trial under the Adocia-Lilly partnership evaluating BioChaperone Lispro, an ultra-rapid
formulation of insulin lispro licensed to Lilly.
This formulation uses Adocia’s proprietary
technology BioChaperone, designed to accelerate insulin absorption.
This study was the first to evaluate BioChaperone Lispro in people with type 2 diabetes (T2D), who, unlike people with type
1 diabetes (T1D), may show various degrees
of disease progression, endogenous insulin
production and insulin resistance. The 14-day
outpatient study aimed to compare the effect
of multiple daily injections of BioChaperone
Lispro and Humalog (insulin lispro rDNA origin) on postprandial glycemic control relative
to solid standardized meals, when injected at
the time of the meal, in 51 people with T2D.
“We are delighted to also observe in people with type 2 diabetes a significantly faster
insulin absorption with BioChaperone Lispro
compared to Humalog, as was the case in our
CREDIT: ELI LILLY AND CO.
WHAT’S INSIDE
MAY 2016 : VOLUME 12 : NUMBER 5
Dr. Thomas Hardy, senior medical director of
endocrinology at Lilly (pictured here), has
been pleased with Phase 1b study results for
BioChaperone Lispro in patients with type 1
and type 2 diabetes, and says Lilly is “pleased
with the expeditious progress of our joint
program with Adocia.”
previous studies in people with type 1 diabetes,” said Dr. Simon Bruce, Adocia’s chief
medical officer. “This acceleration translated,
across more than 200 meal tests, into a significant reduction in postprandial glucose
excursion over the first two hours. These
results underscore that BioChaperone Lispro delivers a similar performance in people
with type 1 or type 2 diabetes. This study also
reinforces comparability in the BioChaperone Lispro safety profile to that of Humalog.”
Based on a post-hoc analysis, BioChaperone Lispro demonstrated a statistically
LISPRO CONTINUED ON PAGE 31
Copyright © 2016 PerkinElmer, Inc. 400341_10 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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MARKET NEWS
MAY 2016 | | DDNEWS 3
Aranca says nano-size will loom large in cancer care
MUMBAI, India—Holding to the age-old
theme that sometimes good things come in
small packages, global research, analytics
and advisory company Aranca, in its recent
report “Nanoparticle Drug Delivery Systems
for Cancer Treatment,” says that “at just one
to 100 nanometres in size, nanoparticles are
the next big thing in cancer treatment.”
Designed to enter tissues at a molecular
level, the firm notes, they can help therapeutic agents pass through biologic barriers,
mediate molecular interactions and identify
molecular changes. Aranca calls it a “bold
new platform for cancer diagnostics and
therapy,” adding that these particles can be
used as carriers in a targeted drug delivery
approach, minimizing drug-originated systemic toxic effects.
“The development and application of engineered nanoparticles to more effectively treat
cancer have witnessed significant advancement over the past several decades,” said
Anup Patwa, an associate for technology and
patent research at Aranca. “Nanotechnology
is a rapidly evolving domain solving various
issues associated with conventional drug
therapeutics, including poor water solubility, lack of targeting capability, non-specific
distribution, systemic toxicity and low therapeutic index.”
However, since their advent in the late
1960s, several nanoparticle-based drugs
are now being clinically used in innovative
therapeutic approaches with notable success. Several nano-formulations of liposomal and PEG-conjugated liposomal, polymeric micelles anticancer drugs have made
the grade, Aranca notes, with some already
approved for clinical use and others undergoing Phase 2 and 3 clinical trials.
As the report says: “Nanoparticles have
promising applications in diagnostic,
therapeutic and drug delivery systems for
cancer, as they can enter the tissues at the
molecular level; these particles have given
platforms for cancer therapy and diagnostics. Nanoparticles provide a new mode for
cancer drug delivery as a carrier for entry
through fenestrations in tumor vasculature,
allowing direct cell access. The modified
nanoparticles allow binding to cancer cell
membranes, microenvironment or cytoplasmic or nuclear receptor sites. This initiates
the delivery of high drug concentrations to
the targeted cancer cell with reduced toxicity of normal tissues. Over the past several
decades, the development and application
of engineered nanoparticles to more effectively treat cancer have witnessed significant
advancement.”
And, while nanoparticles are currently
in an early stage of development, Aranca
asserts: “We expect precisely engineered
nanoparticles to emerge as the next-generation platform for site-specific cancer therapy
and several other biomedical applications. Of
the various nanoparticle cancer drug delivery
systems, liposomes, polymer nanoparticles
and AuNPs would drive cancer drug delivery. Thus, the development of nanoparticle
drug delivery strategies that deliver multiple
drugs using both active and passive targeting approaches to multiple cancer cell sites is
expected to be extremely beneficial.” n
PhRMA addresses delivery of
innovative treatments to patients
WASHINGTON, D.C.—At the Pharmaceuti-
cal Research and Manufacturers of America
(PhRMA) 2016 Annual Meeting in March,
PhRMA President and CEO Stephen J. Ubl
announced the association’s policy solutions for
delivering innovative treatments to patients.
“I am a passionate believer in the power of
biomedical innovation to save and improve
lives,” Ubl said. “We are on the cusp of a
golden era in medical discovery and have
the potential to revolutionize the treatment
of costly and debilitating diseases. But we
can’t take this progress for granted. Now
is the time for PhRMA to play a leadership
role in advancing pragmatic, pro-consumer
policies that enhance the private market and
address costs holistically.”
The proposals in the policy framework are
aimed at modernizing the drug discovery
in drug development and discovery and help
hold down costs for payers and consumers.”
The group had three area of focus in this
area of concern:
ized medicine and regenerative medicine,
hold the promise of treating debilitating diseases such as Alzheimer’s, cancer, diabetes
and many rare disorders.
Encourage use of 21st century tools for
drug evaluation, review and approval—Sci-
Reduce the generic backlog and incentivize competition where needed—A generic
■■
and development process, promoting valuedriven healthcare, engaging and empowering consumers and addressing market
distortions.
While all of those are important, it is the
issue of modernizing the drug discovery and
development process that is most relevant
here at DDNews, and on that front, PhRMA
says that “Pro-patient, pro-science, pro-market
reforms at the Food and Drug Administration
would enhance the competitive market for
biopharmaceuticals, drive greater efficiency
entific advances are reshaping the understanding of the causes of disease, creating
new avenues of research, exploration and
discovery. New and powerful tools emphasize individual patient characteristics and
include innovative clinical trial design,
advanced statistical methods and use of realworld evidence.
■■ Ensure FDA drug approval is scientifically sound and efficient—Medical and
basic science is advancing at a breathtaking
rate. New developments, including those in
immunologic and cell therapies, personal-
“We are on the cusp of a golden era in medical
discovery and have the potential to revolutionize the
treatment of costly and debilitating diseases.
But we can’t take this progress for granted.”
Stephen J. Ubl, president and CEO of PhRMA
■■
drug enters the market at the end of an innovative medication’s lifecycle. When it does,
the FDA allows the manufacturer to submit an Abbreviated New Drug Application
(ANDA), which does not require repetition
of time-consuming and costly clinical trials
the innovative biopharmaceutical company
conducted. As a result, generics can enter the
market at a fraction of the price of an innovator medicine. With nearly 90 percent of all
U.S. retail prescriptions filled with generics,
their timely approval is critical to patient
access and the long-term sustainability of
our healthcare system.
Such issues are critical, PhRMA points out,
because developing an innovative medicine
is a lengthy and complex process, taking an
average of 10 or more years. The clinical trial
component alone takes roughly six to seven
years. With just 12 percent of drugs that enter
clinical trials resulting in an approved medicine, the average research and development
cost for each successful drug is estimated at
$2.6 billion (including the cost of failures). n
MARKET NEWS
Aesica comments on API
manufacturing trends
NEWCASTLE UPON TYNE, U.K.—Aesica
Pharmaceuticals, a leading provider of
contract development and manufacturing
services for active pharmaceutical ingredients (APIs) and finished dosage products
to the pharmaceutical industry, sees the
high levels of regulation, coupled with the
continued evolution of the field, which has
created challenges in the API manufacturing industry, as actually being a great
opportunity to exhibit high quality and
regulatory compliance best practice, and
to continually increase confidence within
the marketplace.
“Competition with low-cost suppliers is
challenging, yet ... represents an opportunity for Western suppliers to continue to drive
operational efficiency through continuous
improvement activities within a controlled
and regulated environment in order to be
competitive,” commented Ian Muir, managing director of Aesica Pharmaceuticals.
“Overall consolidation of contract partners
expands capabilities and allows for greater
control of the supply chain.”
Some pharma ingredient manufacturers
have observed a trend toward companies
preferring to have ingredients manufactured at locations in the West, because of
quality issues in some low-cost markets
recently and the rising costs of production
there. This trend varies according to the
phase of development.
“When introducing new products to the
market, companies tend to favor Western
suppliers in order to mitigate risk. This
trend differs in relation to compounds
which are more advanced in the product life
cycle, such as generic compounds, where
there is more evidence of healthy competition between the East and the West,” Muir
said.
Healthcare firm Consort Medical in
Hemel Hempstead, U.K., acquired Aesica
in November 2014. Consort Medical develops and manufactures medical devices for
drug delivery, including inhaled, nasal and
injectable products through its operating
division Bespak.
“In addition, Aesica offers a contract
manufacturing organization management
service whereby third-party contractors are
managed by Aesica on behalf of a client, creating a single point of contact for the customer, improving visibility and decreasing
supply chain complexity,” explained Muir.
The services that the group now provides
includes finished dose manufacturing, formulation development, API development
and manufacture for drugs, together with
pilot to high-volume manufacturing, prototype development and design for manufacture and concept generation for devices.
“We see growth in API as we continue to
expand upon our current product portfolio through new process introductions and
expansion of our potent manufacturing
capabilities,” Muir concluded. n
MARKET INDICES
Pharmaceutical Index
587
15/May
580
17/Jun
602
16/Jul
593
14/Aug
556
15/Sep
547
16/Oct
540
539
19/Nov
15/Dec
3731
3672
506
15/Jan
482
495
12/Feb
14/Mar
2750
2813
524
22/Apr
Biotechnology Index
4413
4039
4091
4030
4001
3457
15/May
17/Jun
16/Jul
14/Aug
15/Sep
16/Oct
3279
3205
19/Nov 15/Dec
15/Jan
12/Feb 14/Mar
22/Apr
Smoking and drinking reign
over substance abuse pipeline
NEW YORK—The substance abuse treatment pipeline is dominated by therapies for
nicotine and alcohol addiction, with 34 and
32 products, respectively, in active development. Combined, those two markets are
more than half of the total pipeline. Despite
this, there are several promising candidates
in development targeting a range of other
indications, including opioid and cocaine
addiction, according to business intelligence provider GBI Research.
In one of the company’s latest reports,
“The poor understanding
of the brain mechanisms
of addiction represents a
significant challenge in
terms of developing a
highly effective drug, or
combination drugs, for
treating addiction.”
Rodrigo Gutierrez
Gamboa, managing
analyst for GBI Research
it states that various new approaches currently under investigation will see novel
and first-in-class treatments—including
vaccines—redefine the current arena.
A growing treatment pipeline and continued research and investment in this field
reflect the fact that current therapies for
those suffering from various drug addictions remain insufficient, according to GBI.
More than 27 million people worldwide are
currently classified as problem drug users
under the Nations Office on Drugs and
Crime’s guidelines. Of these, only one in six
has access to therapy, while many countries
still have no adequate services for treating
substance abuse.
“One of the main reasons why substance abuse remains high and is so difficult to treat is that there is not yet a
complete understanding of the various
aspects encompassing this global issue,”
said Rodrigo Gutierrez Gamboa, managing
analyst for GBI Research. “Several molecular targets have been identified and have
furthered drug development, but there are
various other targets that are not clearly
understood. The poor understanding of the
brain mechanisms of addiction represents
a significant challenge in terms of developing a highly effective drug, or combination
drugs, for treating addiction.”
Gutierrez Gamboa continues: “The competitive landscape is comprised of both large
pharmaceutical companies and specialized
companies focusing solely on developing
substance abuse treatments, with the top
eight companies comprising Teva, Allergan,
Mylan, Sun Pharma, Sanofi, Psyco Remedies, Rusan Pharma and Aspen Pharmacare.
“Despite the current market focused so
heavily on alcohol abuse, there are significant numbers of products in development
for the treatment of other addictions and
associated withdrawal syndromes. Emerging product segments include cocaine and
opioid addictions, with 26 and 21 pipeline
drugs, respectively, while the cannabinoids
and methamphetamine treatment segments also have several promising drugs
in active development.” n
SOURCE: NYSE ARCA
4 DDNEWS | | MAY 2016
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DISCOVERY
CAMBRIDGE, U.K.—New research published in
the Journal of Biomedical Semantics shows
how clinical knowledge can be incorporated
into bioinformatics software for the task of drug
target discovery. Traditionally, bioinformaticians
derive data from laboratory experiments, but this
research shows that it is possible to include clinical expertise alongside experimental data. A team
from the European Bioinformatics Institute and
the Centre for Therapeutic Target Validation interviewed expert clinicians with the aim of capturing
and including their experience in how phenotypes
were related to autoimmune disorders such as
inflammatory bowel disease. This knowledge was
then mapped into the ontologies used for bioinformatics alongside other relevant data such as
genetic variations studies.
Dr. James Malone, CEO of FactBio and senior
author of the research, said that “This new
approach will allow us to move from the laboratory into the clinic, using not just data but also
the knowledge of those working in the clinic to
improve our understanding of biology.”
CIRM issues grant for
Canavan disease
DURATE, Calif.— The California Institute for
Regenerative Medicine (CIRM) recently made a
$7.38-million grant to City of Hope to support a
research team led by Dr. Yanhong Shi, director
of the Division of Stem Cell Biology Research, in
their efforts to develop a novel treatment for Canavan disease, a rare, fatal neurological disease
that affects infants. Previous work by Shi on this
disease, also funded by a CIRM grant, took stem
cells from Canavan patients and corrected the
genetic defect that causes the disorder. The corrected cells were found to reduce disease impact
when transplanted into mice with Canavan disease. Moving forward, research will be focused
on developing a process that leads to an in-human
clinical trial including stem cell transplantation in
patients using their own reconfigured stem cells.
IN THIS SECTION
Alzheimer’s/Diabetes
Insulin signaling could
link Alzheimer’s and diabetes................... 6
Bioinformatics
Bioinformatics and drug discovery............ 6
Genomics
A first for CRISPR?..................................... 6
CRISPR for the liver................................... 8
Inflammation
Protein p62 puts the brakes on
inflammation.............................................. 6
Neurology
CIRM issues grant for Canavan disease... 6
Insulin signaling could link
Alzheimer’s and diabetes
Mouse models of
Alzheimer’s disease
were found to have
impaired insulin
signaling and insulin
resistance, a
precursor of diabetes
BY KELSEY KAUSTINEN
NEW YORK— While it’s well
known that obesity, high blood
sugar levels and genetics are risk
factors for diabetes, a new factor is
now being brought into the spotlight: Alzheimer’s disease (AD).
Recent research from the Icahn
School of Medicine at Mount
Sinai has found that Alzheimer’s
disease impairs insulin signaling
in the brain, which increases the
risk of developing diabetes.
These results were published
in the paper “Increased susceptibility to metabolic dysregulation
in a mouse model of Alzheimer’s disease is associated with
impaired hypothalamic insulin
signaling and elevated BCAA levels,” which appeared in Alzheimer’s and Dementia. Dr. Christoph
Buettner, associate professor of
medicine, endocrinology, diabetes, bone disease and neuroscience at Icahn School of Medicine
at Mount Sinai, was lead author
of the study. Dr. Henry Ruiz,
a postdoctoral fellow in the
Buettner lab, also collaborated
in the study. This work is part of
ongoing research funded by the
National Institutes of Health.
The most obvious effects of
CREDIT: HOMIEG340, CC BY-SA 3.0
Bioinformatics and
drug discovery
Researchers at the Icahn School of Medicine at Mount Sinai have
found a possible link between Alzheimer’s disease and diabetes.
Pictured here is the Mount Sinai Medical Center.
Alzheimer’s are its degradation
of memory and autonomy, but as
noted in the 2015 article “Metabolic and Non-Cognitive Manifestations of Alzheimer’s Disease:
The Hypothalamus as Both Culprit and Target of Pathology” in
Cell Metabolism: “metabolic and
non-cognitive abnormalities,
SINAI CONTINUED ON PAGE 7
Protein p62
puts the brakes
on inflammation
CREDIT: UC SAN DIEGO
BR IEFS
Pictured here is a cell carrying an RNA-targeted Cas9 system that
reveals beta-actin mRNA distribution in the cytoplasm.
BY MEL J. YEATES
SAN DIEGO—With the rise of
genomics, scientists have been
motivated to sequence the
human genome and develop
ways to DNA; however, many
BY MEL J. YEATES
diseases are linked to RNA. As
RNA is the intermediary genetic
material that carries the genetic
code from the cell’s nucleus, a
challenge has been to find an
efficient method for targeting
RNA in living cells. In a study
published March 17 in Cell,
researchers at the University of
California, San Diego (UCSD),
School of Medicine say they have
SAN DIEGO—As researchers at the University of California,
San Diego (UCSD), School of Medicine note, inflammation
is a catch-22. On the one hand, it is an essential part of eliminating invasive organisms and foreign irritants. On the other
hand, too much inflammation is harmful to healthy cells and
can lead to organ failure and death.
In their efforts to learn to better understand and control the
process of inflammation, those researchers recently discovered
that a protein known as p62 acts as a “molecular brake” to keep
inflammation in check and avoid collateral damage.
The implications of this finding are wide-ranging, notes Dr.
Michael Karin, Distinguished Professor of Pharmacology and
Pathology at the UCSD School of Medicine, who led the study—
published in Cell—with Dr. Zhenyu Zhong, a postdoctoral
researcher in his lab, and collaborators at Sanford Burnham
Prebys Medical Discovery Institute. Among the other study
authors were colleagues from Kyoto Prefectural University of
CRISPR CONTINUED ON PAGE 8
BRAKES CONTINUED ON PAGE 9
A
first
for
CRISPR?
Scientists use
CRISPR-Cas9 to
target RNA in
live cells
Findings could have implications for gout,
atherosclerosis, type 2 diabetes, macular
degeneration, Alzheimer’s disease and cancer
DISCOVERY
SINAI
CONTINUED FROM PAGE 6
such as alterations in body weight
and neuroendocrine functions, are
also present, often preceding the
cognitive decline. Furthermore,
hypothalamic dysfunction can also
be a driver of AD pathology.”
As noted in the recent Alzheimer’s and Dementia paper’s abstract,
“Insulin signaling within the brain,
in particular within the hypothalamus, regulates carbohydrate, lipid
and branched chain amino acid
(BCAA) metabolism in peripheral
organs such as the liver and adipose
tissue.” The team’s hypothesis was
that “cerebral amyloidosis impairs
central nervous system control of
metabolism through disruption of
insulin signaling in the hypothalamus, which dysregulates glucose
and BCAA homeostasis, resulting in
increased susceptibility to diabetes.”
The study was conducted in
mice, and was the first to show that
mice with AD present with insulin
resistance, a precursor to type 2
diabetes, in the hypothalamus. In
the mouse models, the researchers
found that “APP/PS1 mice were
more susceptible to high-fat feeding and aging-induced metabolic
dysregulation including disrupted
BCAA homeostasis and exhibited
impaired hypothalamic insulin signaling.” Elevated levels of branched
chain amino acids (BCAA) in the
blood were also found in these
mouse models, and a previous study
from the Mount Sinai researchers
show that brain insulin signaling
regulates BCAA levels in the blood.
This could denote BCAAs as a biomarker for monitoring insulin signaling in AD patients, though its
potential applicability has yet to be
confirmed in humans.
“Our findings represent a turning
point in the understanding of the
relationship between Alzheimer’s
disease, type 2 diabetes and insulin
resistance,” said Dr. Sam Gandy,
professor of neurology and psychiatry, associate director of the
Mount Sinai Alzheimer’s Disease
Research Center and co-author of
the study. “Compelling and unexpected results such as Dr. Buettner’s
are driving a complete re-evaluation of how these diseases interact.
Now that we have disease genes for
dementia and diabetes, those genes
are our ground zero, and the challenge is to work out all the steps and
missteps between the gene and the
patient and then to find interventions that cure those missteps.”
In other recent work from
Mount Sinai, scientists from the
Icahn School of Medicine and Sage
Bionetworks reported on their collaboration to conduct the largest
genome study to date, consisting
of more than 589,000 genomes.
The team reported their first systematic search across hundreds of
Mendelian disorders in individuals
apparently not inflicted with any of
the disorders to find people carrying disease-protective factors. The
“Now that we have disease genes for dementia and
diabetes, those genes are our ground zero, and the
challenge is to work out all the steps and missteps
between the gene and the patient and then to find
interventions that cure those missteps.”
Dr. Sam Gandy, associate director of the Mount
Sinai Alzheimer’s Disease Research Center
retrospective study was a first step
of the Resilience Project, and was
conducted with scientists from
23andMe, BGI, the Ontario Insti-
tute for Cancer Research and other
institutions.
The team studied DNA from
12 previously collected data sets
using a newly developed targeted
sequencing panel to screen 874
genes for 584 distinct genetic diseases. Those diseases consisted
primarily of metabolic conditions,
neurological diseases or developmental disorders, and all of them
are known to present in childhood
with severe symptoms. All of the
studied genomes came from adults
that had never been diagnosed with
any of the diseases, and the analysis identified 13 healthy individuals with genetic variants associated
WE WROTE
THE BOOK
ON HTRF
Copyright Cisbio Bioassays. All rights reserved. All trademarks are property of Cisbio Bioassays.
with eight diseases.
However, there were roadblocks
with identifying promising individuals. Of the original list of almost
16,000 candidates, more than 75
percent were eliminated due to
inaccurate or low-confidence variant calls in the existing data. Additionally, none of the 13 final candidates could be contacted to confirm
if they were truly resistant to disease
in light of limitations in the original
studies’ informed consent policies. n
EDITCONNECT: E051604
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DISCOVERY
CRISPR for the liver
TARRYTOWN, N.Y. & CAMBRIDGE, Mass.—
With a focus on the liver as the starting point,
Regeneron Pharmaceuticals Inc. and Intellia
Therapeutics Inc. recently announced they
had inked a six-year licensing and collaboration agreement to advance CRISPR/Cas
gene-editing technology for in-vivo therapeutic development.
Under this deal, Regeneron has the exclusive right to discover and develop CRISPRbased products against as many as 10 targets,
focused primarily on therapies for a broad
range of diseases that may be treated by
editing genes in the liver. Of the 10 targets,
Regeneron can select up to five non-liver targets. Non-liver targets from Intellia’s ongo-
“Regeneron’s focus on advancing science to
medicine is an excellent fit with Intellia’s
approach, and together, we aim to bring potential
cures to patients who are suffering from lifethreatening rare diseases and genetic diseases.”
Dr. Nessan Bermingham, CEO and founder of
Intellia Therapeutics
CRISPR
achieved this by applying the popular DNAediting technique CRISPR-Cas9 to RNA.
“This work is the first example, to our
knowledge, of targeting RNA in living cells
with CRISPR-Cas9,” said senior author Dr.
Gene Yeo, associate professor of cellular
and molecular medicine. “Our current work
focuses on tracking the movement of RNA
inside the cell, but future developments could
enable researchers to measure other RNA features or advance therapeutic approaches to
correct disease-causing RNA behaviors.”
David Nelles is a UCSD Jacobs School
of Engineering graduate student in Yeo’s
lab and first author of the study. Study coauthors also include Dr. Jennifer Doudna
and Mitchell R. O’Connell of the University
of California, Berkeley, and Mark Fang, Jia
L. Xu and Sebastian J. Markmiller of UCSD.
RNA’s location in a cell—and how and
when it gets there—can influence whether
proteins are produced in the right location
and at the appropriate time. For instance,
proteins important to neuronal connections in the brain, known as synapses, are
produced from RNAs located at these contacts. Defective RNA transport is linked to
conditions ranging from autism to cancer,
and researchers need ways to measure RNA
movement in order to develop treatments for
these conditions.
Efforts to edit and measure DNA got a
boost a few years ago when researchers
discovered they could take CRISPR-Cas9,
a naturally occurring defense mechanism
bacteria use to fend off other invading bacteria, and use it to edit genes in mammalian systems. Normally with CRISPR-Cas9,
researchers design a “guide” RNA to match
the sequence of a specific target gene. The
RNA directs the Cas9 enzyme to the desired
spot in the genome, where it cuts the DNA.
As Nelles tells DDNews, “CRISPR-Cas9 is a
type of adaptive bacterial immune system
that allows cells to remember viral DNA
sequences so that they can be recognized
and destroyed to prevent infection.”
“This is a great example of an elegant solution in the natural world: bacteria remember
past viral infections by incorporating viral
DNA directly into their own genome, and
then using this DNA to guide Cas9, a scissorlike protein, to cut viral DNA at a later time,”
he continues. “Since CRISPR-Cas9 is specific
enough to recognize specific DNA sequences,
scientists can now cut and correct diseasecausing DNA sequences in human cells.”
Until now, CRISPR-Cas9 could only be
used to manipulate DNA. Yeo and colleagues,
“Our current work focuses on tracking the movement
of RNA inside the cell, but future developments could
enable researchers to measure other RNA features or
advance therapeutic approaches to correct diseasecausing RNA behaviors.”
Dr. Gene Yeo, a professor at UCSD
been historically difficult to address, and
expands our ability to help patients where
antibody-based therapies may not be the
optimal solution.”
Intellia will receive a $75 million upfront
payment and is eligible to receive significant milestone and royalty payments on
potential Regeneron products. Intellia and
Regeneron have agreed to co-develop and cocommercialize a certain number of targets
that are generated during the collaboration.
Transthyretin amyloidosis is the first target
to be jointly developed and potentially commercialized by the companies. Regeneron
has also agreed to invest up to $50 million
in Intellia’s next equity financing.
“We are excited to be partnering with
Regeneron, an industry leader in human
genetics research,” said Dr. Nessan Bermingham, CEO and founder of Intellia Therapeutics. “Regeneron’s focus on advancing
science to medicine is an excellent fit with
Intellia’s approach, and together, we aim to
bring potential cures to patients who are suffering from life-threatening rare diseases and
genetic diseases.”
Intellia is also using the relationship with
such a big biotech player—along with the
Novartis connection—as part of its efforts to
launch a $120-million initial public offering.
As for Regeneron, Zacks Investment
Research noted of the deal: “We remind
investors that Regeneron has been pursuing
strategic collaboration in order to develop
CREDIT: REGENERON
BY JEFFREY BOULEY
ing and planned research, as well as targets
included in another Intellia collaboration, are
excluded from this collaboration. That “other
collaboration” would almost certainly be a
deal forged with Novartis last year that focuses on ex-vivo development of new CRISPR/
Cas9-based therapies using chimeric antigen
receptor T cells and hematopoetic stem cells.
Regeneron and Intellia, in addition to pursuing the discovery, development and commercialization of new therapies, will also put
major effort behind technology development
of the CRISPR/Cas platform itself.
“Our industry-leading human genetics
research with the Regeneron Genetics Center is already identifying important genetic
targets, building on our longstanding expertise in genetic engineering,” said Dr. George
D. Yancopoulos, chief scientific officer of
Regeneron and president of Regeneron
Laboratories. “We believe combining these
capabilities with Intellia’s technology holds
real promise for serious diseases that have
Dr. George D. Yancopoulos, chief scientific
officer of Regeneron and president of
Regeneron Laboratories, foresees the
combination of his companies human
genetics research expertise with Intellia’s
technology as holding “real promise for
serious diseases that have been historically
difficult to address, and expands our ability to
help patients where antibody-based therapies
may not be the optimal solution.”
the candidates in its pipeline. Earlier this
month, the company entered into a licensing agreement with MedImmune, the global
biologics research and development arm of
AstraZeneca plc, to produce antibody drug
conjugates, using MedImmune’s pyrrolobenzodiazepine-based warhead and linker technology for the treatment of cancer.” n
Regeneron and Intellia
announce collaboration to
discover and develop
CRISPR/Cas therapeutics
Researchers at the University of California,
San Diego (pictured here), along with
colleagues at the University of California,
Berkeley, have found a way to use CRISPR
technology to target RNA in live cells.
though, developed a flexible means of targeting RNA in live cells, also called RNAtargeted Cas9 (RCas9). In order to target
RNA instead of DNA, the researchers altered
several features of the CRISPR-Cas9 system.
Building upon previous work by Doudna,
they designed a short nucleic acid called the
PAMmer that, along with the guide RNA,
directs RCas9 to an RNA molecule.
Says Nelles: “The PAMmer is an important
feature of the RCas9 system—it allows strong
recognition of cellular RNA while avoiding
the DNA that encodes it. Cas9 requires two
things to bind a nucleic acid sequence: a
short DNA sequence known as the PAM
(protospacer adjacent motif) and an adjacent
sequence that complements the single guide
RNA. The PAMmer is a short DNA fragment
(with some chemical modifications) that
carries the PAM and hybridizes to the target RNA. By placing a PAM sequence on the
RNA, the PAMmer then allows Cas9 and its
single guide RNA to bind the RNA.”
To test the system, Yeo’s team targeted the
RNA that encodes the proteins ACTB, TFRC
and CCNA2. Then they watched as Cas9,
fused with a fluorescent protein, revealed
the movement of RNA into stress granules,
a cluster of proteins and RNAs that form in
a cell’s cytosol when the cell is under stress.
This system allowed the team to track RNA
over time, in live cells, without the need for
artificial tags commonly used in other RNAtracking techniques—an approach that can
interfere with normal cellular processes.
“To measure RNA distribution in cells,
researchers have to kill cells and treat
them with fluorescent probes, or add extra
sequences to RNAs which can be used to
tag the RNA with fluorescent proteins,” says
Nelles. “While powerful, these techniques
are limited by the fact that either cells must
be killed, or the RNAs need to be genetically
modified. RNA is constantly being produced
and trafficked around cells and genetic modification can be laborious, so a way to track
RNA in living cells without genetic tagging
would be ideal. By fusing a version of Cas9
that does not cut RNA to a fluorescent protein, we were able to track RNA movement
in living cells using RCas9.”
RCas9 could allow researchers to measure
and manipulate a wide range of RNA processing features like RNA transport, splicing,
and turnover—neurogenerative diseases and
certain types of autism are linked to dysfunctional RNA transport in neurons. According
to Nelles, one potential application of this
technique would be tracking RNA transport
in diseased neurons over time, in order to
identify the molecular features of diseases
and support the development of therapies. n
DISCOVERY
Launch of The Hive project
to promote innovation
in early drug discovery
and development
NEW YORK—Elsevier, a global provider
of scientific, technical and medical information products and services, announced
in late April that The Hive, its incubator
project for biotech and pharmaceutical
start-up firms, is now open for nominations and applications.
The Hive is an Elsevier R&D Solutions
collaboration with a select group of biotech and pharmaceutical start-up companies. It aims to showcase the importance
of empowering early-stage drug discovery
and development and demonstrate how
research teams can overcome R&D bottlenecks and challenges.
With up to five firms to be chosen in
2016, participants will benefit, Elsevier
says, from increased visibility of their
work across the pharma R&D community,
as well as enhanced research productivity via complimentary access to Elsevier’s
suite of information solutions, including
user training and support.
“We’ve seen in recent years that over
60 percent of drug discoveries originate
outside the walls of the traditional pharma companies, and almost half of the
industry’s R&D pipelines are externally
sourced—from open-innovation initiatives, from academia or from small bio-
tech start-ups,” commented Alexander Van
Boetzelaer, managing director of Elsevier
R&D Solutions. “The Hive will not only
help highlight innovative start-ups and
give them a platform to promote their
innovation, but also enable the wider pharma R&D ecosystem to learn from these
very young and nimble organizations.”
In addition to providing successful
applicants with increased exposure to the
life-sciences community and complimentary access to Elsevier resources, The Hive
will engage the wider pharma R&D community via case studies and other digital
content featuring the participants, which
will be widely promoted throughout Elsevier’s online and social networks. Individuals and companies following The Hive will
have the chance to hear directly from the
participating companies, while supporting
and learning from their research projects. n
The best candidates for The Hive are
biotech and pharmaceutical start-ups and
other small companies actively engaged
in advancing early-stage research, with
a minimum of three scientists on staff.
Candidate companies may apply or
be nominated for The Hive, and rolling
admissions began in April.
Johnson Matthey and Domainex
collaborate to enhance discovery
and development services
WEST DEPTFORD, N.J. & CAMBRIDGE,
U.K —Johnson Matthey, a provider of
pharmaceutical services, active pharmaceutical ingredients (APIs) and catalyst
technologies, and Domainex Ltd., a smallmolecule drug discovery company, have
announced a collaboration to provide
integrated small-molecule pharmaceutical discovery and development services.
The focus will be on providing academic
institutes, biotechnology and pharmaceutical companies across the United Kingdom
and beyond with effective, simplified,
rapid and reduced-risk target-to-lead identification, optimization, safety/toxicology,
preclinical and clinical API supply services.
Domainex is a leading provider of smallmolecule drug discovery services that
complement the preclinical to commercial range of services provided by Johnson
Matthey Fine Chemicals’ Custom Pharma
Solutions offering in Europe, the companies note. Through an integrated offering
co-located in the Cambridge region, customers will be able to access Domainex’s
target-to-lead identification and optimization capabilities, and will then be able to
transfer their projects directly to Johnson
Matthey, utilizing its Pharmorphix solid-
state services for effective salt form and
polymorph identification through to process development, scale-up and non-GMP
toxicology manufacture. With all activities co-located in the Cambridge area, discovery and development time and risk can
be greatly minimized.
“Johnson Matthey and Domainex have
together recognized there is customer
demand for simplified and effective drug
discovery and development services. With
our combined expertise and facilities
based in Cambridge, we are now able to
offer customers significant value through
this joint service offering,” said Antoine
Bordet, European managing director at
Johnson Matthey Fine Chemicals.
“The transition from drug discovery
and candidate nomination into polymorph
screening, preclinical toxicology and Phase
1 clinical development is a critical phase
in the drug development process,” added
Tom Mander, chief operating officer of
Domainex. “We’re bringing together the
necessary complementary people, skills
and facilities with Johnson Matthey so that
together we can offer an integrated and simplified solution spanning pharmaceutical
discovery through to clinical development.” n
BRAKES
a role in a rare form of Parkinson’s disease.”
“In terms of therapeutic potential, we think
that drugs that could increase the mitophagy/
autophagy pathway (in which p62 and Parkin
play critical roles) would be beneficial for a
number of human inflammatory diseases,
such as gout, atherosclerosis, type 2 diabetes,
macular degeneration, Alzheimer’s disease
and cancers, because these disorders are all
associated with hyper-activation of the NLRP3
inflammasome,” adds Zhong. “Testing the
effect of autophagy-enhancing drugs would
be a good direction to go in the future.” n
Medicine and Cedars-Sinai Medical Center.
Macrophages play a major role in
inflammation—they detect and swallow
invading microbes and foreign particles.
Activated macrophages release cytokines,
small proteins that serve as signals to recruit
and activate other immune cells for assistance.
To produce and secrete one major inflammatory
cytokine, interleukin-1beta (IL-1beta),
macrophages employ molecular machines called
inflammasomes. One of the most functionally
diverse inflammasomes is the NLRP3
inflammasome, which releases IL-1beta when
stimulated by toxins and microparticles such
as silica, asbestos or cholesterol microcrystals.
One thing Karin and colleagues found
was that foreign particles don’t act directly
on the NLRP3 inflammasome, but instead
damage the macrophage’s mitochondria.
These damaged mitochondria then respond
by releasing signals that activate the NLRP3
Pictured is a macrophage (yellow, center) in
the liver. Macrophages play a major role in
inflammation, and researchers at UCSD have
begun to understand how to put the brakes
on destructive inflammatory processes.
inflammasome and its production of IL-1beta.
In the short run, that’s beneficial for the
body, but continuous production of IL-1beta
can lead to a chain reaction that results in
multi-organ failure, septic shock and death.
And this is where p62 comes into the
picture, because as Karin’s team discovered,
to turn off IL-1beta production by NLRP3
inflammasomes, macrophages responding
to foreign microbes and irritants also begin
production of p62.
Zhong tells DDNews that p62 inhibits
IL-1beta production, functioning as an
autophagy adaptor that binds to damaged
mitochondria, thereby promoting autophagic
clearance of these mitochondria. Once
these damaged mitochondria are removed,
the NLRP3 inflammasome deactivates and
IL-1beta production ceases.
The damaged mitochondria also activates
Parkin—a protein that in humans is encoded
by the PARK2 gene—which is required
for p62 recruitment onto the damaged
mitochondria. The Parkin ubiquitinates
multiple mitochondrial outer membrane
proteins. Then p62 is recruited to the
damaged mitochondria by binding to these
ubiquitinated mitochondrial proteins.
Thus, p62 functions as an adaptor that
delivers the damaged mitochondria to
autophagosome/lysosome, where they
are eventually degraded, says Zhong, who
continues: “We’ve suspected for quite some
time that damage to mitochondria caused by
either genetic or environmental factors is the
root cause of many age-related diseases, all of
which are associated with chronic, low-grade
inflammation. Therefore, p62—and its part in
eliminating damaged mitochondria—could
provide a new target for preventing such
diseases. We already know that Parkin plays
MTI-GlobalStem
EDITORIAL
The ironic agonies of pain relief
O
Spray, a non-steroidal anti-inflammatory drug
F ALL THE MANY emails and news for short-term management of pain that requires
releases I receive about poten- analgesia at the opioid level.
Along with that, a news release in my inbox
tial therapeutics, from discovery
through clinical trials, what strikes from Collegium Pharmaceutical Inc. announced
FDA approcal of Xtampza ER (oxyme at times isn’t so
codone) extended-release capmuch what I see, but what I don’t see.
sules which use the proprietary
Sure, there are innumerable
DETERx technology platform for
announcements and news tidbits
abuse-deterrence.
about cancer treatments and neuroThese and products like them from
logical disorders and many others,
other companies are important, I
but what I don’t see much of is word
know. Pain is a condition that needs
about pain relief.
to be managed for the good of patients,
Or rather, I don’t see much new
and opioids play a necessary role. But
on that front.
why, I wonder, do I see so little of
This was brought home to me this Jeffrey Bouley,
DDNews Chief Editor
research on new pathways for pain
month with an email from Elliot Fox,
director of media and engagement for Egalet management compared to other therapeutic areas?
There are hints of hope, however, that make
Corp, which is working to develop treatment
alternatives to the commonly abused pain medi- me feel I may see more of that in the future.
cations currently available. As Fox wrote, “As Another email I received recently spoke about
we all have seen, there is a rise in the abuse of presentations by leading scientific experts who
opioid medications, and something needs to be will be at Pain Therapeutics 2016, with several
done. Egalet is strategically working to provide exclusive presentations on key evolving theraa solution by developing an abuse deterrent—or pies, among them updates on the preclinical
an ‘indestructible’— pill that provides patients and clinical development of selective sodium
suffering with pain a safer treatment option.” channel blockers, clinical translation success in
Among its products on the market now are trials for capsaicin-based remedies and smallOxaydo tablets for oral use only that are formu- molecule Nav1.7 inhibitors, among other things.
For now, the relative dearth of pain relief
lated to deter abuse via snorting and Sprix Nasal
BY JEFFREY BOULEY
news continues, but I hope to see a shift soon
in my inbox.
By way of awkward transition, let me conclude by telling you about the commentaries
on the following few pages and the “pains” they
involve—or don’t. For one, just below this editorial, DDNews Features editor (and bi-monthly columnist) Randall C Willis speaks of the discomfort
of anecdotes vs. evidence, when so often people
latch on to highly touted “remedies” in the news
and social media feeds that are often more rumor
or hype than actual promise. However, even in
the anecdotes, he notes, we sometimes find the
beginning of wisdom that leads to development
and clinical testing of potential therapeutics.
On page 11, a guest commentary about dealing
with the pains of processing massive amounts of
information through data visualization.
Finally, on page 12, something far from pain.
Spurred on by my editorial a couple issues ago,
titled “A cancer cavalcade for March,” Dr. Joe
Olechno, a senior research fellow with LabCyte,
sent me a thorough breakdown of an alternative
to the personalized medicine model for cancer. I
can say it is a genuine pleasure to have provoked
such a lengthy response—essentially a commentary in itself. I can’t say I’ve ever received feedback that came complete with lengthy references.
May your reading of this issue be filled with
insights and encouragement—and no pain. n
www.DDN-News.com
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OUT OF ORDER: A STORY
ABOUT ANECDOTES
BY RANDALL C WILLIS
“The plural of anecdote
is not evidence.”
I
T IS an adage that is quoted often in medi-
cal and drug development circles as a stalwart against crackpots, snake-oil salesmen
and patients desperate for a Hail Mary
miracle when all of the standard options
have failed to alleviate their suffering. It has all
the hallmarks of the parental comeback: “And
if your friend Billy decided to jump off a bridge,
you’d jump off, too?”
As a recidivist biochemist and long-time
science and medicine writer, I spend an inordinate amount of time repeating this adage to
friends who post the craziest things on Facebook or Twitter. Rarely, on deeper scrutiny, do
these medical miracles show signs of scientific
thinking or investigative rigor. More often
than not, the evidence of success is a series of
undocumented testimonials about how much
weight someone lost or the renewed joy of
playing piano or traveling with a loved one.
(Not unlike most advertising by pharmaceutical companies.)
In some ways, it
seems, it is less about
making lemonade out
of lemons so much as
making lemonade out
of quartz crystals.
cer activity over the years,” Marcus
By the same token, on rare occarecounts, “but about 10 or 15 years
sions, the lack of a clinical trial does
ago, the University of Utah discovnot necessarily mean a lack of cliniered that if you combine disulfiram
cal relevance.
with heavy metals, it chelates the
This morning, I watched a news
heavy metals and that the chelate has
item about a young girl who suffered
very potent anticancer properties.”
an extreme form of epilepsy, a form
Subsequent studies showed that
that sent her into seizures every few
when combined with copper, disulminutes. From birth, this poor girl
firam has very potent activity in gliowas crushed by hundreds of seizures
blastoma (GBM). Having purchased
every day, and none of the typical Randall C Willis
the IP from the University of Utah,
medications given for epilepsy or
pain seemed to work for very long, if at all. Her Cantex is now working with Washington University in St. Louis and has initiated trials in
mother was desperate.
For reasons not clearly explained in the news recurrent GBM.
“The wonderful thing about this is that it will
item, the mother decided to try her daughter on
oils extracted from medicinal marijuana (infused not be a $100,000 drug,” he enthuses. “We’re
into coconut oil). It worked. The daughter’s sei- repurposing an old drug, and it will be more
zures ceased within hours and have continued to affordable than most things.”
Marcus is the first to admit, however, that
be controlled for two years and running.
Is this evidence of a new treatment for her despite having some ideas of what the drug
condition? No. It is an anecdote of one patient’s does in the cell (e.g., proteasome inhibition and
induction of reactive oxygen radicals), they do
experience.
But for at least this one patient, it is a clini- not have a clear mechanism of action, which he
says puts it on par with most chemotherapeutics.
cally relevant anecdote.
“For many of the chemotherapy drugs, the
Back in the 1920s, a compound used in the
vulcanization of rubber was also found to induce mechanism of action is unclear,” he explains.
an intense sensitivity to alcohol consumption in “Sometimes people will cite a mechanism of
factory workers; an instant hangover. Eventu- action, but then others will say then why would
ally, the compound was identified as disulfiram, it work in Cancer A but not Cancer B.”
“So there’s a lot that’s unknown; it’s just
and by the 1960s, it was marketed as an aversion
empirical,” he continues. “I think empiricism
therapy to treat alcoholism.
But the anecdotal echoes didn’t stop there, is going to play a big role in future cancer drug
according to Stephen Marcus, CEO of Cantex development; finding something that works or
Pharmaceuticals, with whom I spoke at AACR somebody who has an unusual way of looking
at something.”
2016 in New Orleans.
“There were scattered reports about anticanORDER CONTINUED ON PAGE 11
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EDITORIAL
COMMENTARY:
Data
visualization
New directions or just
familiar routes?
BY EDMUND J. CHAMPNESS, CHIEF
D
SCIENTIFIC OFFICER OF OPTIBRIUM
ATA VISUALIZATION tools make
it very easy to represent our data
graphically and present it in a
way that clearly communicates
patterns and trends. But, there
is a risk that visualizations may be used,
in practice, to confirm or justify our own
hypotheses and biases. Instead, can data visualizations bring to light patterns in our data,
drive new hypotheses and show us things we
weren’t expecting?
Given the efficiency with which we can process visual information, it is easy to explain
the appeal of data visualization. At its best,
a visualization can highlight patterns which
numerical analyzes might otherwise miss.
Anscombe’s quartet (Anscombe, 1973) is a
good example of four data sets which are statistically very similar, but which when visualized
show very different relationships. This sanity
check can be invaluable, and yet it should be
remembered that inappropriate choices of plot
type, axis scales or directions and color can
result in visualizations which might be uninformative or misleading at first glance. Our
ability to spot visual patterns quickly can work
against us when an inappropriate visualization
is presented, whether or not the creator was
attempting to mislead us deliberately.
If we consider a drug discovery project
for which we have measured potency data, a
common question to ask might be “On which
compounds should I focus my attention?” We
will illustrate this using an example set of 264
compounds, representing six different chemical series, for which 5-HT1A activities have
been measured. The examples in Figure 1 show
the importance of choosing an appropriate way
to represent the range of potencies across the
chemistries. The simple histogram shown in
A gives a good overview but tells us nothing
about how the potencies are distributed across
the chemical series, until we introduce some
color, as in B. This still isn’t very clear, given
the different number of compounds in each
chemical series, whereas using a two-dimensional histogram in C and D the height of each
bar shows the average potency of a chemical
series. The choice of y-axis scale also influences
our view of the data, and in C the chemical
series look almost identical, whereas in D there
appear to be significant differences—but what
is the “right” range? In E, having chosen a range
based on a potency level we might consider as
“inactive to very active,” we can also see the
importance of adding error bars to give some
indication as to the distribution of potencies.
This highlights the value of representing these
data using a box plot instead, as in F. Now it
becomes clear that each series contains some
potent compounds, but the indole-3-alkylamines certainly appear to be the most active.
Of course, potency is just one of the properties we would need to consider in order to
identify a high-quality lead compound, and in
our data set we also have predicted values for
a number of typical absorption, distribution,
metabolism and excretion and physicochemical properties. While we could create a box
plot for each property of interest, this would
require us to look at and, most importantly,
make sense of a large number of visualizations. We could attempt to put many dimensions of data into single a scatter plot—three
dimensions plotted with others represented
by color, size, transparency, etc.—but unless
there are some very obvious outliers, it is
likely to be very hard to interpret.
It is worth considering, therefore, the kind
of information with which we typically make
decisions in drug discovery. All of the proper-
Figure 2. Plot of compound scores ordered from left to right with errors shown. The chemical
series highlighted above dominate the top scoring compounds.
ORDER
In some ways, it seems, it is less about
making lemonade out of lemons so much
as making lemonade out of quartz crystals.
Just because we don’t understand why
something works in an unexpected application, we shouldn’t automatically dismiss
Figure 1. Different ways to visualize the potencies for a small library of compounds highlighting
the value of choosing appropriate plot type, axis scales and color.
ties used to analyze and select compounds are
derived from models of the ultimate human
patient in which we are interested, whether
those models are in vivo, in vitro or in silico. All
measured data, however accurate, will contain
some degree of uncertainty due to experimental
variability, while in-silico models will contain
some statistical error. As an example, a good
root-mean-square error for an aqueous solubility
prediction represented as logS(µM) is approximately 0.6. In practice, this means that a logS
value of 1 (corresponding to 10µM) represents
a fairly soluble compound but which we only
know with 95-percent confidence has an actual
aqueous solubility somewhere between 630mM
and 0.16nM. Knowing that the real value lies
towards one end of the range or the other might
have a significant impact upon a decision we
make about selecting this compound.
And this is just a single property. It is
common to base compound selection decisions on criteria for multiple properties. At
their simplest, these criteria might just be
cutoffs when we believe that an acceptable
compound will have a property value on the
“right” side of a threshold. When we consider
the uncertainty around our data points, even
a value on the “right” side of the threshold
might have some probability of being unacceptable. In some cases, poor property values
with high uncertainties may even represent
better opportunities for optimization than
On rare occasions, the lack of a clinical
trial does not necessarily mean a lack of
clinical relevance.
any suggestions that it does.
Ironically, it is who we are, as much of
what we know as the modern pharmaceutical industry was built on such serendipitous
observations and anecdotal folklore.
So, while it remains true that the plural
of anecdotes is not evidence, it can be a
good starting point. And because, in so
very accurate values which fall just short of
the necessary criteria.
Adding this information about uncertainty
into any data visualization will improve its
representation of the true nature of the data,
but this comes at the cost of interpretability.
Just adding error bars to our plots isn’t likely
to solve this problem.
One approach to dealing with this is to use
multiparameter optimization (MPO) to generate a score that encapsulates multiple properties. There are several approaches to MPO
(Segall, 2012), but by using one that explicitly considers the uncertainty, we can significantly reduce the number of dimensions we
need to visualize. Applying this to the set of
5-HT1A compounds, a single visualization can
now represent all of the underlying data, giving a more comprehensive picture of which
chemical series have the greatest potential. In Figure 2, the compounds have been
scored and plotted from left to right in order
of descending score. We can see error bars
which indicate when we can select between
compounds with confidence, but the two
highlighted series (arylpiperazines and aminotetralines) are represented by green and
pink points, which dominate the left-hand
side of the plot where the highest scores lie.
This is despite these series not including the
most potent compounds, as shown in the
DATA CONTINUED ON PAGE 13
many ways, the outcome is more important than the process in healthcare, we
have a duty to at least considering that
these stories might be simply the first
superficial signs of a mountain of undiscovered evidence. n
Randall C Willis can be reached by email at
willis@ddn-news.com
The opinions expressed in guest commentaries do not necessarily represent those of DDNews and/or its owners, editors or other staff.
EDITORIAL
COMMENTARY: Individualized
medicine vs. precision medicine
inates this problem and reproducibly generates
the best therapy for a patient’s particular cells.
BY DR. JOE OLECHNO, SENIOR RESEARCH
T
FELLOW, LABCYTE INC.
HERE ARE PEOPLE who will die of
cancer this week even though there
are drugs that could help them.
At the same time, hundreds
of patients will undergo cancer
chemotherapy that, while debilitating and
expensive, will not cure them of their disease.
While cancer is a formidable foe, there is
a way to improve patient care and prognosis
immediately.
Researchers in Finland, Sweden and Spain
have modified ex-vivo testing of cancer cells
with significant results. Their approach is far
more “personalized” than traditional precision
medicine. Their results are striking. They provide a missing link between genomics-based
mutation determination and clinical efficacy.
Precision medicine (also referred to as
“personalized medicine” or PM) appears to
many patients, doctors and researchers to be
a golden highway from disease identification
to cure. The idea of interrogating the genome
of a particular cancer to determine its Achilles
heel is intuitively satisfying and understandable. There are, however, significant problems.1,2,3 First, PM is neither personalized nor
precise. PM strives to identify the appropriate
biomarker (usually a DNA mutation but proteins, peptides and metabolites can stand as
biomarkers as well) to categorize the patient
as a member of a specific group of patients. The
patient is treated with a drug that has shown
positive results on previous members of the
group. In other words, personalized medicine
is actually population-based medicine.
In contrast, the method described by
researchers at the Institute of Molecular Medicine, Finland, determines empirically the best
treatment with what they call “individualized”
medicine to differentiate it from PM. They
follow the determination of the appropriate
therapy with detailed genomics-based analyses of the patient and the cancer to develop
an understanding of the mode of action of
the therapy. By integrating the cure with an
understanding of the genetic mutation, they
have changed the existing paradigm and created “individualized system medicine.” The
power of the individualized system medicine
approach includes the ability to more quickly
look at mechanisms of action, assess drug
combinations, understand drug resistance,
position and de-risk drug candidates and
provide more rapid drug repositioning in a
way that has not been previously achievable.4
There are three critical problems with
genomics-based PM. Two of these problems are
intrinsic to the biology. Genomics-based science
has identified exciting new methods of treatment and I do not call for its abandonment, but
rather adding to the process the critical step of
ex-vivo testing to mitigate some of the deficiencies inherent with genomics approach alone.
Problem 1—Mutations in DNA are
not clear signs of the cause of the
cancer (or disease)
Typically, genomic analysis is used to determine what mutation causes the cancer.
Sometimes the therapy works and at other
times, the patient goes through debilitating
chemotherapy only to find that there was
no impact on the cancer. In fact, the cancer
may have grown and further mutated during the time of the treatment, gaining both
mass and genetic changes so that it is even
harder to treat with supplementary rounds
of chemotherapy.
While it may seem obvious that if you
sequence the tumor and find the genetic
flaw that causes the cancer, addressing that
flaw specifically should result in remission.
In fact, this desired outcome is sometimes
achieved. Yet despite the apparent causal
relationship between mutation and cancer,
clinicians often do not see a good correlation
between the identification of the genomic
mutation and successful treatment.
Researchers at the Wellcome Trust Sanger
Institute and their colleagues have observed
that healthy skin tissue—tissue that appeared
normal by any measure—was full of somatic DNA mutations. DNA mutations in the
apparently healthy skin were found at the
same level as the mutations in tumor cells.5
Not only did a quarter of all the healthy skin
cells carry a cancer-causing mutation, but
the researchers found that these mutations
were under strong positive selection—that is,
the number of cells carrying the mutations
tended to increase even though there was no
evidence of cancer.
This means that when an oncologist finds
a cancer-causing mutation, it may not be the
cause of the cancer jeopardizing the health
of the patient. It may just be along for the
ride. But giving a drug targeted to the harmless mutation delays getting the drug that
will actually stop the cancer. All the while,
the initial cancer drug may cause damage to
healthy cells.
Similarly, researchers at Johns Hopkins
showed that DNA analysis of tumor cells
tended to produce many false positives.6
They suggest that comparing the mutations
in apparently healthy tissue with that of the
tumor will determine the true, cancer-causing genes. Unfortunately, the data from the
Wellcome Trust Sanger Institute mentioned
above suggests that healthy tissue contains
many different mutations, and it is unlikely
that there is a single healthy genotype to use
for comparison.
Simply put, evidence of the existence of a
mutation is not evidence of a cause for cancer.
Treating a patient based on a latent mutation
may harm the patient and delay helpful
treatment.
Problem 2—Inability to reconcile
genomic data and phenotypic results
Two extremely good labs, the Cancer Genome
Project and the Cancer Cell Line Encyclopedia, analyzed the DNA of hundreds of different cell-lines. They also tested the cell lines
against many different drugs to see how they
responded. The data from both labs was analyzed by Quackenbush and colleagues7 who
found that their genomic results were spoton. Both labs obtained very similar results
when they analyzed the DNA from the same
cell lines. However, when these labs tested
identical drugs against these cell lines, they
obtained dramatically different results. If one
lab found that a particular drug was effective
against a target in a cell line, the same analysis in the other lab, more frequently than not,
gave contradictory results.
This means that even if finding DNA mutations meant that you could choose a particular target or enzyme to block in the treatment
of a cancer, you might not be able to choose
the right drug. Each lab could end up choosing a different treatment due to the difficulty
in determining the correlation between drug
and response.
It is important that the two labs obtained
almost identical results in their DNA analyses. This shows that they both use consistent
scientific methods that others can replicate.
One assumes that if they can match results
analyzing DNA, they should also be able to
get equivalent results in drug response experiments. The fact that they do not suggests
that the problem is not something as simple
as competence in scientific technique.
A recent publication in Nature Biotechnology8 highlighting that certain individuals are
resilient to Mendelian childhood diseases
despite clear genomic evidence of the presence of the specific mutation is just another
example of DNA sequence alone not providing sufficient proof of disease. This paper
amplifies the impact of problems 1 and 2.
By adding critical information, the ex-vivo
individualized systems medicine approach elim-
Problem 3—Personalized medicine falls
back to guessing if no drug has
previously been found effective against
a cancer associated with a new
genomic mutation
Assuming that you correctly determine the
mutation causing the cancer among all the
other somatic mutations in the sample, you
may find a mutation for which no chemotherapy has been determined. The pharmacogenomic process can point you only to treatments that have already been verified. That
means that the drug of choice has been tested
in double-blind experiments and has gone
through the required government licensing
procedures for that particular cancer. While
the number of therapies continues to grow,
the personalized medicine pathway would
miss (and would never even look to try) that
some cancers can be cured by drugs not associated with a particular cancer. In essence, you
would need to test all drugs against all cancers,
a herculean feat with most existing protocols.
Personalized medicine would not have pointed a doctor to using thalidomide9 or methotrexate10 against particular cancers, but individualized systems medicine can help uncover
new uses for existing drugs in an orderly way.
For example, researchers at the Institute for
Molecular Medicine, Finland (FIMM) have
shown that the antiangiogenic renal cancer
drug axitinib11 can be repurposed against
T315I-mutant BCR–ABL1-driven leukemia.
Guessing is still just guessing even if there is
genomic data. Having phenotypic results that
show which drug or drug combinations kill a
patient’s particular cancer is a significant advance.
A Reasonable, Cost-Effective
Complement to Genomics-Driven Testing
Finding a mutation does not necessarily
mean finding the cause of the cancer. And
even if the cause of the cancer is identified
correctly, it is not easy to determine which
drug will be effective against that mutation.
What is the alternative?
Researchers at FIMM12,13,14,15,16,17 and
elsewhere have turned the question on its
head. Instead of trying to identify a mutation
in the DNA and then trying to find a drug
that addresses that mutation, they isolate
cancerous cells from the patient. They then
test those cancerous cells against hundreds of
possible drugs to see which drugs are effective
against the cancer. In some cases, they use
cocktails of drugs to see if the combinations
are more efficacious than single drugs. They
frequently test the drugs at many different
concentrations to better understand the
potential dosing aspects.
Just because a drug works against isolated
cancer cells ex vivo does not necessarily mean
that it will work inside the body. However,
the inverse of that statement, that if it does
not work on cells ex vivo it is unlikely to work
in the patient, is most likely true. This is what
the researchers found. By screening the drugs
against the patient’s cancer cells, they found
DNA CONTINUED ON PAGE 13
DNA
other cancer drugs that were able to drive
the cancer to remission while saving patients
from ineffective treatments. Most significantly,
this was true even in patients who had already
failed multiple rounds of chemotherapy.
Chemotherapy has both monetary and
health costs whether or not it leads to a cure.
First-line treatments can fail and force the
patient to alternatives. Every new round of
treatment eats away at the window of opportunity to cure the disease.
The researchers at FIMM have developed an empirical, individualized test that
can screen hundreds to thousands of drugs
against a patient’s particular cancer quickly
and at low cost. The test can eliminate chemotherapy that is highly likely to fail and
it informs the clinician of the best options.
With DNA analyses, as they describe in their
papers, individualized systems medicine can
help expand the understanding of cancers
and guide future drug discovery.
While labs in Finland, Sweden18 ,19,20 and
Spain21 are already investigating the technique, more labs should be moving this forward. As a member of a family that has been
struck multiple times by cancer, I hate to think
that I would need to book a flight to Finland in
order to get the best options for chemotherapy.
Testing drugs for efficacy before starting
chemotherapy will reduce costly but futile
rounds of therapy. It would also identify
active drugs and let the patient and doctor
make secondary decisions on price. This
REFERENCES
1. Joyner MJ. Moonshot medicine will let us down. New
York Times. 2015 Jan 29:A27.
2. Van Driest SL, Wells QS, Stallings S, Bush WS, Gordon
A, Nickerson DA, Kim JH, Crosslin DR, Jarvik GP, Carrell
DS, Ralston JD. Association of arrhythmia-related genetic
variants with phenotypes documented in electronic medical
records. JAMA. 2016 Jan 5;315(1):47-57.
3. Husten L. Precision Medicine, Stuck In Second Grade,
Flunks Test Of Clinical Utility, CardioBrief, 2016 January 5,
http://cardiobrief.org/2016/01/05/jama-study-precisionmedicine-flunks-test-gets-left-back-in-second-grade
4. Pemovska T, Östling P, Heckman C, Kallioniemi O,
Wennerberg K. INDIVIDUALISED SYSTEMS MEDICINE.
Drug Discovery. 2015:47.
5. Martincorena I, Roshan A, Gerstung M, Ellis P, Van Loo P,
McLaren S, Wedge DC, Fullam A, Alexandrov LB, Tubio JM,
Stebbings L. High burden and pervasive positive selection
of somatic mutations in normal human skin. Science. 2015
May 22;348(6237):880-6.
6. Jones S, Anagnostou V, Lytle K, Parpart-Li S, Nesselbush
M, Riley DR, Shukla M, Chesnick B, Kadan M, Papp E,
Galens KG. Personalized genomic analyses for cancer
mutation discovery and interpretation. Science translational
medicine. 2015 Apr 15;7(283):283ra53-.
7. Haibe-Kains B, El-Hachem N, Birkbak NJ, Jin AC,
Beck AH, Aerts HJ, Quackenbush J. Inconsistency in
large pharmacogenomic studies. Nature. 2013 Dec
19;504(7480):389-93.
8. Chen R, Shi L, Hakenberg J, Naughton B, Sklar P, Zhang
J, Zhou H, Tian L, Prakash O, Lemire M, Sleiman P. Analysis
of 589,306 genomes identifies individuals resilient to severe
Mendelian childhood diseases. Nature Biotechnology. 2016
Apr 11. doi:10.1038/nbt.3514
9. Richardson P, Hideshima T, Anderson K. Thalidomide:
emerging role in cancer medicine. Annual review of
medicine. 2002 Feb;53(1):629-57.
10. Thomas S, Fisher KH, Snowden JA, Danson SJ, Brown
S, Zeidler MP. Methotrexate is a JAK/STAT pathway
inhibitor. PloS one. 2015 Jul 1;10(7):e0130078.
11. Pemovska T, Johnson E, Kontro M, Repasky GA, Chen
J, Wells P, Cronin CN, McTigue M, Kallioniemi O, Porkka K,
Murray BW. Axitinib effectively inhibits BCR-ABL1 (T315I)
with a distinct binding conformation. Nature. 2015 Mar
5;519(7541):102-5.
12. Pemovska T, Kontro M, Yadav B, Edgren H, Eldfors S,
Szwajda A, Almusa H, Bespalov MM, Ellonen P, Elonen E,
Gjertsen BT. Individualized systems medicine strategy to tailor
treatments for patients with chemorefractory acute myeloid
leukemia. Cancer discovery. 2013 Dec 1;3(12):1416-29.
EDITORIAL
could increase competition and drive down
prices, especially on those drugs that show
little if any efficacy.
While PM may give lip service to nongenomic assays, by far the greatest effort
and the largest number of dollars are being
directed towards using genomic markers to
determine healthcare. In part, this is because
the success of the Human Genome Project.
Excellent scientists from the NIH, NCI,
academia and private industry combined to
provide the first full human DNA sequence.
The question then was, “What’s next?”
With hundreds of sequencers purchased
and thousands of molecular biologists now
trained, how could all these resources be
put to good (and desired by the public) use?
Healthcare was the obvious choice. But to
the hammer, everything is a nail.
I believe that there is a role for genomic
analyses in healthcare, I just do not think that
it will be the panacea that many suggest. I
am especially concerned that excellent tools,
like those developed by FIMM, are not being
used by researchers locked into solely the
genomic pathway.
I urge clinicians and researchers to explore
the work begun in Finland. The procedures
are straightforward and the results can be
rapidly available. The technique offers the
promise of increased remissions, reduced
failure of chemotherapy and decreased
healthcare expense. A multilevel winning
strategy uniting ex-vivo testing with
genomics-based analyses appears within our
grasps, and we need to take hold. n
13. Tang J, Karhinen L, Xu T, Szwajda A, Yadav B,
Wennerberg K, Aittokallio T. Target inhibition networks:
predicting selective combinations of druggable targets to
block cancer survival pathways. PLoS Comput Biol. 2013
Sep 12;9(9):e1003226.
14. Yadav B, Pemovska T, Szwajda A, Kulesskiy E, Kontro
M, Karjalainen R, Majumder MM, Malani D, Murumägi A,
Knowles J, Porkka K. Quantitative scoring of differential
drug sensitivity for individually optimized anticancer
therapies. Scientific reports. 2014 Jun 5;4.
15. Pietiainen V, Saarela J, von Schantz C, Turunen L,
Ostling P, Wennerberg K. The High Throughput Biomedicine
Unit at the Institute for Molecular Medicine Finland:
High Throughput Screening Meets Precision Medicine.
Combinatorial chemistry & high throughput screening. 2014
May 1;17(4):377-86.
16. Pietarinen PO, Pemovska T, Kontro M, Yadav B,
Mpindi JP, Andersson EI, Majumder MM, Kuusanmäki H,
Koskenvesa P, Kallioniemi O, Wennerberg K. Novel drug
candidates for blast phase chronic myeloid leukemia from
high-throughput drug sensitivity and resistance testing.
Blood cancer journal. 2015 May 1;5(5):e309.
17. Kulesskiy E, Saarela J, Turunen L, Wennerberg K.
Precision Cancer Medicine in the Acoustic Dispensing Era
Ex Vivo Primary Cell Drug Sensitivity Testing. Journal of
laboratory automation. 2016 Feb 1;21(1):27-36.
18. Blom K, Nygren P, Alvarsson J, Larsson R, Andersson CR.
Ex Vivo Assessment of Drug Activity in Patient Tumor Cells
as a Basis for Tailored Cancer Therapy. Journal of laboratory
automation. 2015 Aug 5:2211068215598117.
19. Eriksson A, Österroos A, Hassan S, Gullbo J, Rickardson
L, Jarvius M, Nygren P, Fryknäs M, Höglund M, Larsson
R. Drug screen in patient cells suggests quinacrine to be
repositioned for treatment of acute myeloid leukemia. Blood
cancer journal. 2015 Apr 1;5(4):e307.
20. Sylvan SE, Skribek H, Norin S, Muhari O, Österborg
A, Szekely L. Sensitivity of chronic lymphocytic leukemia
cells to small targeted therapeutic molecules: An in vitro
comparative study. Experimental hematology. 2016 Jan
31;44(1):38-49.
21. Bennett TA, Montesinos P, Moscardo F, MartinezCuadron D, Martinez J, Sierra J, García R, de Oteyza JP,
Fernandez P, Serrano J, Fernandez A. Pharmacological
profiles of acute myeloid leukemia treatments in patient
samples by automated flow cytometry: a bridge to
individualized medicine. Clinical Lymphoma Myeloma and
Leukemia. 2014 Aug 31;14(4):305-18.
Figure 3. Comparison between SAR tables and activity neighborhood for optimizing
potency and stability.
DATA
histograms below the representative compound displayed for each series.
The visualization of any complex data
set is problematic, but even much smaller
sets can present challenges. If we consider
a subset of the 5-HT1A compounds, comprised of the drug Buspirone and a small
number of analogs, we might hope to
determine relationships between their
structures and two important properties,
potency and metabolic stability. The goal
in this case is to identify structure-activity
relationships (SAR) to design a potent, stable compound. Carrying out an R-group
analysis and creating an SAR table for each
property (Figure 3 A and B), we can quickly see that the combinations of R-groups
which result in the highest potency do not
give the best stability, and vice-versa (in
both cases, the greenest circles represent
the best values). On the other hand, if
we create an activity neighborhood diagram, Figure 3 C, we can visualize the
relationships between the compounds in
a different way. Choosing a representative
compound with average potency and stability values to be at the centre, the other
compounds are organised in a spiral with
the most structurally similar closest to
the middle. The cards are colored by their
metabolic stabilities, with green being the
highest. The links show the difference in
potency, with green showing the greatest difference and the arrow showing the
direction in which the potency increases.
Therefore, a green arrow pointing towards
a green card, indicating a more potent and
stable compound, easily stands out. Using
this approach quickly highlights the original problem, that simply moving a single
functional group can modify a compound
from being “stable and not potent” to
“unstable and potent.” The compound that
stands out, however, which is both potent
and stable, but not easily apparent from
the SAR table, results from a combination
of changes—an important point that may
otherwise have been overlooked.
At each decision point, the choice of
visualization can be pivotal. The way we
perceive our compounds depends upon
those around it: Have we explored the
surrounding chemical space thoroughly
enough to adequately evaluate a series? Do
we have data of sufficient quality to confidently distinguish the good compounds
from the rest? When it comes to making
decisions about compounds, it is often the
relationships between compounds that will
influence the way we choose the next compound. Any visualizations which simplify
or hide these relationships have the potential to bias our perception of the data. n
Edmund J. Champness is chief scientific
officer of Optibrium Ltd. With a background
in Mathematics, he joined GlaxoWellcome
in 1995 working as part of a pioneering
team building predictive pharmaceutical
tools. He developed the first graphical
user-interfaces for working with predictive
models, which were adopted globally
within GlaxoWellcome. He was a core
member of the team which established
the U.K. operation of Camitro in 2001 and
remained with that company through a
series of mergers and acquisitions (ArQule,
Inpharmatica and BioFocus DPI) until
2008. During this time, he designed and
built the StarDrop software and, in 2009,
co-founded Optibrium.
REFERENCES
1. Anscombe, F. (1973). Graphs in Statistical Analysis.
American Statistician, 27(1), 17-21.
2. Segall, M. (2012). Multi-Parameter Optimization:
Identifying high quality compounds with a balance of
properties. Current Pharmaceutical Design, 18(9), 1292-1310.
Inovio, Wistar Institute ink
deal for DNA-based products
PLYMOUTH MEETING, Pa.—A series of collabora-
tive research agreements have been announced
between Inovio Pharmaceuticals Inc. and the
Wistar Institute focused on preventive and
therapeutic DNA-based immunotherapy applications and products for cancers and infectious
diseases developed by Dr. David B. Weiner and
his lab at Wistar. Inovio will gain the exclusive
right to in-license new intellectual property developed under this collaboration. This deal will not
affacted Inovio’s license agreements for intellectual property developed at UPenn.
“This new agreement with Wistar starts a
whole new chapter of Inovio’s R&D leadership
in one of the most important emerging medical
technologies: DNA-based immunotherapies. We
congratulate Dr. Weiner with respect to his multiple new roles at Wistar and the significantly
expanded lab and resources available to him
to continue pursuing his life’s passion. We look
forward to a long and fruitful relationship with
this eminent institution to continue advancing
cutting-edge DNA-based immunotherapies and
DNA-based monoclonal antibody technology,”
said Inovio President and CEO Dr. J. Joseph Kim.
INFORS HT to distribute
Cell Growth Quantifier
BOTTMINGEN, Switzerland—INFORS HT has assumed
sole responsibility for the global distribution of
aquila biolabs’ Cell Growth Quantifier (CGQ),
which enables non-invasive online monitoring of
biomass in shake flasks. The CGQ can determine
biomass concentration automatically, optically
and non-invasively through the vessel wall using
a patented sensor and provide detailed microbial
growth kinetics in up to 16 shake flasks simultaneously and in real time. In addition, it is compatible
with all INFORS HT shakers and clamps as well as
with “Sticky Stuff” products and all common types
of glass and transparent single use flasks in the
sizes 250, 300, 500, 1000 and 2000ml can be used.
IN THIS SECTION
Antibodies
Identification key to reproducibility......... 14
Biomass monitoring
INFORS HT to distribute
Cell Growth Quantifier............................. 14
Immunotherapy
Inovio, Wistar Institute ink deal
for DNA-based products.......................... 14
Oncology
Shooting for three strikes not to be out..... 16
Peptide drug design
Looking ahead with PepSee.................... 15
Virtual collaboration
Strategically going digital ...................... 14
Strategically going digital
Collaboration
between Dassault
and Inserm is
designed to
advance the use
of ‘virtual trials’
BY ILENE SCHNEIDER
PARIS — A joint agreement
between Dassault Systèmes
a n d t h e Fre n c h
National Institute of
Health and Medical
Research (Inserm)
will use a “virtual collaborative platform”
to advance research
in the areas of cancer, aging,
genomics and microbiota and to
advance the use of “virtual clinical trials.” At the core of these
initiatives is an integrated virtual
environment for open collaborative research, unified laboratory
management and biological and
chemical modeling and simulation from Dassault Systèmes’
flagship brand BIOVIA.
Inserm, the only French public research institute to focus
entirely on human health, had a
need for a scientific platform to
validate its scientific models in
the process of the development
of new clinical trial technologies,
according to Reza Sadeghi, BIOVIA’s chief strategy
officer, a member of
the U.S. Department
of Energy National
Review Board and
an adjunct professor
at University of California, San Diego. Inserm will
work with Dassault Systèmes to
offer new perspectives on how
to best address today’s scientific
and health challenges.
Created in 1964, Inserm is a
TOOLS &
TECHNOLOGY
INSERM CONTINUED ON PAGE 17
CREDIT: INSERM
BRIEFS
Inserm (a researcher of which is pictured here) will rely on Dassault
Systèmes for all software to help manage its labs and perform
biological and chemical modeling and simulation. Dassault Systèmes
will also pull in information from Inserm research programs to help
calibrate and validate scientific models it sees supporting the
development of new technologies.
Identification key to reproducibility
Antibody Registry project gains
momentum, new commercial partners
BY ZACK ANCHORS
SAN DIEGO—A project aimed at
establishing a single, standard
format to identify all antibodies has a new ally:
ImmunoStar, a supplier of primary antibodies for neuroscience research. The
Hudson, Wis.-based
company is one of
the first antibody manufacturers
to fully sign on to the Antibody
Registry’s effort to improve identifiability and reproducibility in
research papers by attaching a
unique and persistent code to
each antibody.
The Antibody Registry assigns
a unique and persistent identifier called an Research Resource
Identifier (RRID) to each antibody so that it can be referenced
within publications. ImmunoStar has committed to attaching
RRIDs to each of its antibodies
to ensure those antibodies can
be traced and identified when
they are used in research. For
example, ImmunoStar’s 5-HT
(Serotonin) Rabbit Antibody
#20080 is identified
as RRID:AB_572263.
The registry is one
facet of a broader
NIH-funded project
launched in 2014
called the Resource
Identification Initiative (RII).
The program is pushing for the
use of RRIDs for citations of
antibodies as well as for two
other categories of research
resources: model organisms and
tools, including software and
databases.
Anita Bandrowski, specialist
at the University of California,
San Diego, and group leader of
RII, says the goal of the project
is to partner with research journals and vendors to attach RRIDs
to as many research resources
as possible. “It works like a
TOOLS &
TECHNOLOGY
“It works like a social security
number,” says Anita Bandrowski,
group leader of the Resource
Identification Initiative, of
Research Resource Identifiers.
“RRIDs allow us to track a
resource even if the company the
produced it changes name or if
the product changes hands.”
Such a process could, among
other things improve and
reproducibility in research papers.
social security number,” she
says. “RRIDs allow us to track a
resource even if the company the
produced it changes name or if
the product changes hands.”
The potential for RRIDs to
effectively track antibodies
regardless of company renaming
and reselling is a main reason for
ImmunoStar’s support of the registry. ImmunoStar has changed
its name during its 35-year history and has a product line that
includes numerous antibodies
that were previously associated
with other company names.
RII is also intended to tackle
other widely recognized problems in biomedical research
stemming from the lack of consistent and detailed citations. It
is often difficult to identify which
resources were used in a given
study, a challenge that undermines the reproducibility of the
research and that prevents others
from reusing the same resource.
RII cites as an example of the
problem infrequent reporting of
the catalog numbers for antibody
reagents and the omission of the
version numbers for software
programs used for data analysis.
The use of RRIDs appears to be
RRID CONTINUED ON PAGE 16
LOOKING AHEAD WITH PEPSEE
Zealand, BioSolveIT
unveil software tool
for therapeutic
peptide research
and development
BY KELSEY KAUSTINEN
COPENHAGEN, Denmark & SANKT
AUGUSTIN, Germany—A European
team-up between Zealand Pharma
A/S and BioSolveIT has resulted
in the creation of a novel, unique
software tool designed to enhance
and advance the design, research
and development of therapeutic
peptides. By combining Zealand’s
experience in peptide design and
BioSolveIT’s chemical informatics
software capabilities, the companies have produced PepSee. With
regard to PepSee, BioSolveIT will
own the software while Zealand
will hold a free user license for its
application and integration into
Zealand’s design skills and peptide
knowledge database.
The first version of PepSee has
already been launched at Zealand,
and the completion of a second
version is expected within 18
months, the company says. The
ultimate goal is for this tool to
combine visual computational peptide modeling, design and modality
prediction capabilities with biological and physio-chemical data to
“PepSee is a perfect
example of
BioSolveIT’s core
expertise: creating
fast, visual and
user-friendly
software tools which
have the potential to
deliver rapid
improvements to
scientific innovation.”
Dr. Marcus
Gastreich, director
of application
science at BioSolveIT
support faster and more advanced
therapeutic peptide research and
development.
“PepSee is a perfect example of
BioSolveIT’s core expertise: creating fast, visual and user-friendly
software tools which have the
potential to deliver rapid improvements to scientific innovation,” Dr.
Marcus Gastreich, director of application science at BioSolveIT, said in
a press release. “We are delighted
that Zealand, with its world-recognized excellence in therapeutic
peptide research and design, has
chosen to work with us to shape
the most relevant tool possible. We
believe that this tool will add new
dimensions to advanced
peptide design.”
Peptides, chains of
amino acids, play a variety of essential roles in
numerous physiological
processes. Medicinal
peptide research uses pattern recognition and structural optimization of peptides to aid in the design
of novel compounds with promis-
ing properties for therapeutic use. Despite the
promise of this branch
of research, however,
software support for the
field is limited.
“We are delighted
to work with BioSolveIT on this
unique project. It is part of our
strategy to continuously expand
TOOLS &
TECHNOLOGY
PEPTIDE CONTINUED ON PAGE 17
Zealand Pharma teamed up with BioSolveIT in the creation of a software
tool called PepSee that is designed to enhance and advance the design,
research and development of therapeutic peptides.
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Shooting for three
strikes not to be out
SRI and Stanford to explore new molecular target
for treatment of triple negative breast cancer
MENLO PARK, Calif.—Triple-negative breast
ImmunoStar, a supplier of primary antibodies for neuroscience research, is one of the first
antibody manufacturers to fully sign on to an effort to improve identifiability and
reproducibility in research papers by attaching a unique and persistent code to each antibody.
RRID
gaining ground. Thousands of articles using
RRIDs can be found in research databases
and 100 journals have agreed to encourage authors to use them. “Not all the participating journals are enforcing at the same
level, but an increasing number are asking
authors to use them,” says Bandrowski. “The
more partners we can get on board—both
on the manufacturers side and the journal
side—the more valuable the whole project
becomes for everyone involved, including
the antibody companies, which are very
interested in research validating or invalidating their products.”
Bandrowski tells DDNews that she anticipates many more antibody manufacturers to
begin actively supporting the use of RRIDs
as they learn more about the advantages.
She cited BioLegend, the San Diego-based
antibody and reagent manufacturer, as one
company that will soon be joining Immuno-
CREDIT: STANFORD HEALTH
cancer is a particular problem, as it represents some 20 percent of such cancer cases,
and its tumors are unresponsive to hormone
therapy or drugs targeting the three most
common receptors that tend to drive breast
cancer progression. A new collaborative project between scientists at SRI International
and physician-researchers from the Stanford
Cancer Institute aims to solve—or at least
reduce—that problem through efforts that
will support development of novel drugs for
treatment of triple-negative breast cancer.
The research collaboration will explore
the use of a preclinical drug known as sudemycin D6 that targets, as the collaborators
put it, a “molecular machine” called the
spliceosome. The spliceosome is critical to
the basic biological transformation of DNA
to RNA to proteins, they say, as it “edits”
raw RNA transcribed from DNA, cutting
and piecing together stretches of code to
form the instructions for creating various
functional proteins.
SRI and Stanford liken the process to
that of a film editor producing a finished
movie from raw footage. If this biological
editor complex is defective, proteins that
ultimately result from its actions can be dysfunctional and lead to various forms of cancer, including triple-negative breast cancer.
And that’s where the research team—led by
Dr. Thomas R. Webb, director of medicinal
thing wonderful for patients with cancer:
new treatments that are more effective and
less toxic,” said Dr. Sledge.
Webb’s research group designed sudemycin D6 to neutralize the SF3B1 protein of the
spliceosome with enhanced activity and duration of action as well as less toxicity than previous spliceosome targeting agents. The team
has also developed a marker tumor cell line
that fluorescently glows when treated with
sudemycin D6. This advance enables realtime monitoring of the drug’s activity, which
will support translation to the clinical setting.
The SRI Biosciences and Stanford Cancer
Institute collaboration is the first step in determining whether sudemycin D6 may be effective against triple-negative breast cancer.
This work is an expansion of efforts already
ongoing between the two organizations. It
was just a few months ago, in early January, that SRI and Stanford announced they
would team up to enhance drug development
efforts in response to a lack of innovative new
treatments for cancer and other diseases.
And even that partnership built on previous collaborations between the two institutions. For example, the development of Tirapazamine, an experimental cancer therapy,
was made possible by the teamwork of SRI
and SCI researchers.
The Drug Discovery and Development
Program formed in January is coordinated
by Sanjay V. Malhotra, associate professor of
radiation oncology at Stanford, and Nathan
CREDIT: IMMUNOSTAR
BY JEFFREY BOULEY
A newly announced effort by SRI International and Stanford Health to tackle triple-negative
breast cancer builds off a partnership announced in January, the debut of which is pictured here.
chemistry at SRI Biosciences, a division of
SRI International, and Dr. George Sledge,
professor and chief of the Division of Oncology at Stanford University Medical Center—
is directing its attention.
“As both a medicinal chemist and cancer
survivor, I know that new treatments are desperately needed for cancer,” said Webb. “It is
my greatest hope that we can combine the
unique strengths of SRI Biosciences and the
Stanford Cancer Institute to make long-lasting impact in the treatment of triple-negative
breast cancer, where unfortunately there are
currently few effective therapeutic options.
The strategy may also work for a range of
other cancers, including lymphoma, melanoma, and certain brain and colon cancers.”
“Stanford and SRI both have unique
strengths, and together we can create some-
Collins, executive director of the Pharmaceutical and Chemical Technologies Section
in SRI Biosciences.
“The SCI-SRI Biosciences collaboration
provides a fully integrated engine for taking
ideas to the investigational new drug stage
and beyond,” Collins said. “Our focus is on
developing ‘first-in-class’ drugs and delivering improved outcomes for patients.”
SRI Biosciences integrates basic biomedical research with drug and diagnostics discovery and preclinical and clinical
development. For its part, SCI is a National
Cancer Institute-designated Cancer Center
advancing understanding of cancer and
rapidly translate research discoveries into
improved prevention strategies, diagnostics
and therapies. n
Star as a fully participating vendor.
One of the first researchers to include
RRIDs in published research was Dorota
Skowronska-Krawczyk with the Department
of Ophthalmology at the University of California, San Diego. She also says she uses the
registry when searching for new antibodies
to use in her research. “It gives me confidence that people are using [the antibody]
and citing it,” she explained in a press release
issued by ImmunoStar.
RRIDs are designed to be convenient
and easy to use for both authors and those
trying to identify cited resources. RII has
created an online Resource Identification
Portal that provides access to a range of
databases, including The Antibody Registry.
When a researcher finds the resource they
need to cite, they can click on a button that
enables the proper citation to be inserted
into their paper. They also have the ability
to create an RRID for a new resource using
the portal. n
Certara launches new
e-learning platform for
biosimulation education
PRINCETON, N.J.—Certara, a global biosimulation
technology-enabled drug development company,
recently launched an e-learning platform through
Certara University to satisfy the increased need
for education in the burgeoning field of biosimulation, or model-based drug development. With
the addition of this new on-demand content, scientists from all over the world, with differing skill
levels in biosimulation, will be able to access
the educational assets developed by Certara’s
scientific leaders, the company says.
“The use of biosimulation in drug development has evolved from being a research nicety
to a regulatory necessity,” said Certara CEO
Dr. Edmundo Muniz. “In fact, the U.S. Food and
Drug Administration and European Medicines
Agency have recommended biosimulation in
more than a dozen draft regulatory guidance
documents and its use is now expected by
regulators. As sponsor companies increase
their use of biosimulation to inform pivotal
drug development decisions and interact with
regulators, ongoing education is becoming of
paramount importance to ensure they optimize
their application of this technology.”
“Biosimulation’s rapid adoption has created
a growing global demand for education in pharmacometrics theory and technologies,” added
Nathan Teuscher, Certara’s vice president of scientific training. “We are proud to be expanding
Certara University’s reach by providing e-learning
classes so we can continue to share our knowledge and experience with drug development
researchers around the world in the most effective formats available.”
In addition to the recognized advantages of
being able to take a class at the most convenient
time with no travel involved, the biosimulation
e-learning courses also allow participants to gain
access to world-class trainers and learn at their
own pace, Certara says, citing data from Applied
Cognitive Psychology magazine indicating that
deeper learning occurs when participants can
control the rate at which they move through
segmented content. In addition, Certara notes,
the Research Institute of America reports that
e-learning increases information retention rates
by up to 60 percent. n
INSERM
public institution with a scientific and
technical mission under the dual auspices of the French Ministry of Health and
the Ministry of Research. It was created
as a successor to the French National
Institute of Health. Inserm consists of
339 research units, run by 6,500 permanent staff members. Eighty percent of
Inserm research units are embedded in
research hospitals of French universities.
With a budget of €989 million in 2014,
Inserm supports more than 300 laboratories across France.
BIOVIA’s systems are designed to integrate the diversity of science, experimental processes and information requirements across research, development,
QA/QC and manufacturing, according to
Sadeghi. Capabilities include scientific
data management; biological, chemical
and materials modeling and simulation;
open collaborative discovery; scientific
pipelining; enterprise laboratory management; enterprise quality management; environmental health and safety;
and operations intelligence.
Per the terms of the agreement,
Inserm will rely on Dassault Systèmes for
all software to help manage its laborato-
Inserm is a public institution with a
scientific and technical mission under
the dual auspices of the French Ministry
of Health and the Ministry of Research. It
was created as a successor to the French
National Institute of Health and consists
of 339 research units, run by 6,500
permanent staff members.
ries and perform biological and chemical
modeling and simulation, Sadeghi says.
Data will flow in the opposite direction,
with Dassault Systèmes pulling in information from Inserm research programs
to help calibrate and validate scientific
models it sees supporting the development of new technologies.
By utilizing the 3DEXPERIENCE platform, which uses Microsoft technology,
Inserm will conduct strategic biomedical
research programs for cancer, genomics,
aging and microbiota. The 3DEXPERIENCE platform will offer an integrated
virtual environment for collaborative
research, as well as unified laboratory
management and biological and chemical modeling and simulation.
Dassault Systèmes plans to use Big
Data from Inserm’s research programs
“[We] will establish open collaboration on a social
scientific platform and address the strategic
scientific challenges of Inserm. Expected benefits are
in the area of clinical solutions, with access to patient
clinical and omics data and scientific challenges.”
Reza Sadeghi, chief strategy officer for Dassault
Systèmes BIOVIA brand
PEPTIDE
Zealand’s peptide competencies, and
the first version of PepSee has already
demonstrated its potential to support
innovation and enhance our efficiency
in the design of novel peptide therapeutics. More importantly, as more
features are added, we will push further the boundaries of peptide discovery and development. BioSolveIT has
a strong reputation for innovation,
usability, and quality of service and we
look forward to finalizing the development of this unique peptide research
software tool,” Britt Meelby Jensen,
president and CEO at Zealand, commented in a statement.
In other recent product news
from BioSolveIT, the company has
announced that SeeSAR 4.2 for SAR
and lead optimization is now available. This software tool offers “interactive, visual compound prioritization as well as compound evolution.
Structure-based design work ideally
supports a multi-parameter optimization to maximize the likelihood of success, rather than affinity alone. Having the relevant parameters at hand
in combination with real-time visual
computer assistance in 3D is one of
the strengths of SeeSAR,” BioSolveIT
notes on its website.
The new release offers a variety of
features, including updated covalent
binder handling, in which ligands
to calibrate and validate scientific models that can be applied to future technologies in clinical research. Because of
this data and the scientific models, Dassault Systèmes will be able to develop
industry solution experiences that target clinical trials, helping to accelerate
decision-making.
In the words of Yves Lévy, chairman
and CEO of Inserm, “We seek out technologies that further our mission to
observe and understand mechanisms of
the living body and ultimately transfer
this knowledge to therapeutic solutions
for new and mutating diseases that are
affecting the world’s growing population. We lead long-term, competitive
scientific programs in human health and
medicine and the Dassault Systèmes’
3DEXPERIENCE platform will help us
support collaboration, project management, data, resources, traceability and
other processes.”
“A virtual collaboration platform
works by catalyzing scientific research
through patient-centric numerical
models, leveraging information intelligence and translational medicine Big
Data informatics,” Sadeghi says. “In this
collaboration we will establish open collaboration on a social scientific platform
and address the strategic scientific challenges of Inserm.”
“Expected benefits are in the area of
clinical solutions, with access to patient
clinical and omics data and scientific
challenges,” Sadeghi adds. “Other benefits include linking biosystems behavior
knowledge and understanding the clinical outcome of therapeutics.” n
“It is part of our strategy to
continuously expand Zealand’s peptide
competencies, and the first version of
PepSee has already demonstrated its
potential to support innovation and
enhance our efficiency in the design
of novel peptide therapeutics.”
Britt Meelby Jensen, president and
CEO at Zealand
are not static but optimized in the
HYDE Visual Affinities framework;
the ability to process protein-ligand
PDB files automatically, with ligands
carved out and assessed with HYDE;
augmented platform support with
an MS Windows 64bit version; control over when HYDE Affinities are
computed; and enhanced filtering as
well as more space for loading in SD
properties.
Zealand Pharma posted its full year
2015 financial results mid-March,
reporting a fourth quarter with revenue of €22 million and a net result
of €9 million. For the full year 2015,
the company’s net result was a loss
of €15 million, compared to a loss
of €9 million for full year 2014, and
revenues of €25 million, compared
to €21 million in 2014.
“2015 was one of the best years
in the history of Zealand. Financial
results were as expected with considerable financing from milestone payments, and our business and portfolio have substantially progressed.
Under our agreement with Sanofi,
both lixisenatide and LixiLan have
been filed for approvals in the U.S.
with regulatory decisions expected
in July and August, respectively …
We have also advanced and expanded our own proprietary pipeline,
including the initiation of Phase 2a
trials with two new lead drug candidates, a glucagon analogue for hypoglycemia and a GLP-2 analogue for
short bowel syndrome,” said Britt
Meelby Jensen, president and CEO
of Zealand. n
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PRECLINICAL
PDS releases turnkey
solution for SEND datasets
Paratek makes
headway towards
new broadspectrum antibiotic
MOUNT ARLINGTON, N.J.— PDS Life Sciences
recently announced the launch of SEND Express,
a turnkey solution for the generation of Standard
for Exchange of Nonclinical Data (SEND) datasets.
The launch is tied to the FDA deadline for standardized electronic data submissions. By Dec. 17,
2016, all datasets from studies supporting new
drug applications, biologics license applications
and abbreviated new drug applications must be
submitted to the FDA in SEND format. PDS SEND
Express enables pharmaceutical companies and
contract research organizations to meet FDA
SEND requirements without having to invest
in software and staff training. PDS’ preclinical
scientists and data analysts use TranSEND to
accelerate data integration and harmonization
into SEND-compliant datasets.
BY ZACK ANCHORS
BOSTON—Paratek Pharmaceuticals has announced positive data
from two preclinical trials that
bode well for its 15-year-long quest
to develop a broad-spectrum antibiotic. The Boston-based company, which became publicly traded
last year after a reverse merger
with Transcept Pharmaceuticals,
released preclinical data in April
suggesting that its compound
omadacycline was less likely than
other broad-spectrum antibiotics
to induce serious gastrointestinal
Preclinical data supports further
development of ALD1613
bacterial infections such as Clostridium difficile.
Omadacycline, the first in a
new class of tetracyclines known
as aminomethylcyclines, is currently undergoing two Phase
3 trials, one for acute bacterial
skin and skin structure infections (ABSSSI) and another
for community-acquired bacterial pneumonia (CABP). Paratek
expects data from the ABSSSI
trial to be announced in the next
several months and data from the
CABP trial to be available in the
second half of 2017.
Paratek Chief Medical Officer and President Evan Loh tells
DDNews that the company is
well positioned to move omaPARATEK CONTINUED ON PAGE 19
CREDIT: PARATEK
End in sight for omadacycline
BR IEFS
It’s been a 15-year-long quest for the broad-spectrum antibiotic
omadocycline, but Paratek Chief Medical Officer and President Evan
Loh says, “Transitioning from a private company to a publicly traded
company listed on NASDAQ has allowed us to bring an amount of
capital that the company has never had access to previously,” and
that, along with some new preclinical data, is pushing the compound
forward in Phase 3 trials.
BOTHELL, Wash.—Alder BioPharmaceuticals Inc.
recently presented preclinical data for ALD1613, an
anti-adrenocorticotropic hormone (ACTH) antibody
for the treatment of congenital adrenal hyperplasia and Cushing’s disease. ALD1613 was found to
inhibit ACTH-induced cortisol secretion in a mouse
adrenal cell line in vitro, and administration in rats
with artificially elevated ACTH and corticosterone
levels let to a rapid, durable reduction of plasma
corticosterone levels. In non-human primates,
ALD1613 demonstrated stable, durable reductions
in plasma cortisol levels by more than 50 percent.
“Existing therapeutic options for patients with
congenital adrenal hyperplasia and Cushing’s
disease comprise treatments that provide limited disease control and involve significant side
effects. We believe these limitations indicate a
clear need for new therapies such as ALD1613,
which targets ACTH to diminish the overproduction of cortisol,” said Dr. Randall C. Schatzman,
Alder’s president and CEO.
Preclinical positivity for Prothena
Antibodies against misfolded transthyretin
successfully bind misfolded proteins,
recognize amyloid deposits in vitro
BY KELSEY KAUSTINEN
DUBLIN, Ireland—Clinical bio-
technology company Prothena
Corporation plc recently published preclinical data showing
that its conformation-specific
antibodies developed against
misfolded transthyretin (TTR)
bind to and facilitate in-vitro
cellular uptake of amyloidogenic
forms of TTR. The paper, titled
“Novel conformation-specific
monoclonal antibodies against
amyloidogenic forms of transthyretin,” appeared online in the
journal Amyloid.
Transthyretin-mediated amyloidosis (ATTR amyloidosis) is a
rare, progressive disease characterized by the deposit of aggregates of misfolded protein, or
Age-related disease
Mitochondria-based therapeutics
against aging........................................... 21
Amyloidosis
Preclinical positivity for Prothena........... 18
Antibiotics
End in sight for omadacycline................. 18
Datasets/FDA
PDS releases turnkey
solution for SEND datasets..................... 18
Disease models
Bioprinting frontier.................................. 20
Hyperplasia/Cushing’s disease
Preclinical data supports
further development of ALD1613............ 18
CREDIT: PROTHENA
IN THIS SECTION
amyloid. There are three types of
ATTR amyloidosis: familial amyloid polyneuropathy, familial amyloid cardiomyopathy and wildtype (or senile systemic) ATTR.
The first two are hereditary and
can occur concurrently, but wildtype ATTR is not hereditary.
TTR protein is produced primarily in the liver. In its normal
tetrameric form, it serves as a
carrier for thyroxin and vitamin
A. In hereditary familial amyloid polyneuropathy and familial amyloid cardiomyopathy, the
body produces a mutant form
of the TTR protein. Wild-type
ATTR is similar to hereditary
ATTR, except that the deposited protein is a misfolded, nonmutated transthyretin protein.
“Our preclinical data demonstrate that
these antibodies are highly selective for
the misfolded form of TTR, can prevent
fibril formation and can potentially
recruit immune cells to clear amyloid
fibrils from tissue,” says Dr. Gene Kinney,
chief scientific officer and head of R&D at
Prothena, of his company’s
conformation-specific antibodies.
Recent Prothena preclinical data demonstrate that its antibodies are
highly selective for the misfolded form of TTR and could offer an important
complement to other therapies for TTR amyloidosis in development.
“One of the fundamental challenges of developing an effective
treatment for many amyloid diseases, including ATTR amyloidosis, is creating a therapeutic
that not only reduces circulating
levels of the misfolded protein,
but one that can also prevent
the formation of new fibrils and
facilitate the elimination of fibrils
that have deposited in tissue and
cause progressive organ failure,”
said Dr. Gene Kinney, chief scientific officer and head of research
and development at Prothena.
“Our preclinical data demonstrate that these antibodies are
highly selective for the misfolded
form of TTR, can prevent fibril
formation and can potentially
recruit immune cells to clear
amyloid fibrils from tissue. This
could offer an important complement to other therapies for TTR
amyloidosis in development.”
The work focuses on monoclonal antibodies that specifically
PROTHENA CONTINUED ON PAGE 20
PRECLINICAL
PARATEK
dacycline through the final stages
of development after many years
of delay.
“Transitioning from a private
company to a publicly traded
company listed on NASDAQ has
allowed us to bring an amount of
capital that the company has never
had access to previously, and that
has allowed us to go forward with
Phase 3 development for omadocycline,” he says.
Loh notes that a primary reason for the delayed development
of omadacycline has been past
regulatory uncertainty caused by
unclear FDA guidelines regarding
how new antibiotics are evaluated. Regulatory hurdles for Paratek
were somewhat alleviated in 2012
when Congress passed the Generating Antibiotic Incentives Now Act
(GAIN), which clarified the drug
approval process in an effort to
address the need for new drugs to
“All the big pharma
companies had
rotated out of
developing new
antibiotics because
of various regulatory
uncertainties, and
Paratek lost nearly
five years of work
time developing
this compound due
to regulatory
uncertainty. But now
we are working
tirelessly and
energetically to
move this
compound forward.”
Evan Loh, president
and chief medical
officer of Paratek
fight antibiotic-resistant bacteria.
“All the big pharma companies
had rotated out of developing new
antibiotics because of various regulatory uncertainties, and Paratek
lost nearly five years of work time
developing this compound due to
regulatory uncertainty,” Loh tells
DDNews. “But now we are working
tirelessly and energetically to move
this compound forward.”
One of the risks of using broadspectrum antibiotics is that most
commonly used classes of these
drugs have a strong potential to
increase a patient’s risk for superinfections like C. difficile. This risk
has caused many hospitals and
physicians to scale back use of
antibiotics.
“Even though antibiotics may
cure a patient’s infection, they
may present one to four weeks
later with C. difficile, which can be
debilitating, and in some high-risk
populations it can be life-threatening,” says Loh.
Paratek announced data from
two preclinical trials at the European Congress of Clinical Microbiology and Infectious Diseases
in Amsterdam that addressed the
risk of bacterial infection. One
study, which evaluated the impact
of omadacycline on gastrointestinal
flora, showed that the compound,
despite extensively disrupting the
gut microbiome, has a low propensity to induce C. difficile infection.
A separate study found that omadacycline exhibited potent in-vitro
activity against C. difficile. Both
studies were led by Mark Wilcox,
a professor of medical microbiology
at the University of Leeds.
The new preclinical findings
support Paratek’s predictions that
omadacycline could have an advantage over other broad-spectrum
antibiotics due to a lower pro-
pensity to cause gastrointestinal
infections. Risk of infection has
historically been low in patients
treated with the class of antibiotics known as tetracyclines, and the
new study provides new evidence
that this is specifically the case with
omadacycline.
“Similar to other tetracyclines,
it appears that the aminomethylcycline omadacycline has a low
potential risk of inducing C. difficile infection, suggesting that it
may offer an advantage for patients
who need treatment with a broadspectrum antibiotic in serious community-acquired infections where
resistance is of concern,” said Loh
in a news release.
Omadacycline is being developed as a once-daily oral and
intravenous antibiotic. In addition to its efforts to develop the
compound for ABSSSI and CABP,
Paratek is also pursuing its development for urinary tract infection
and sinusitis. n
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PRECLINICAL
BIOPRINTING FRONTIER
SAN DIEGO—Organovo Holdings Inc. pre-
CREDIT: ORGANOVO
sented five sessions at the Society of Toxicology’s (SOT) 55th Annual Meeting and
ToxExpo, March 13 to 17, in New Orleans
to demonstrate the broad applicability of its
exVive3D Human Liver Model for the assessment of drug safety and the detection of clinically relevant modes of liver injury, including
steatosis and fibrosis.
Organovo, which is “a marriage of engineering and biology,” uses 3D bioprinting
technology to develop three-dimensional
human tissues aimed at “delivering scientific and medical breakthroughs,” according to
Paul Gallant, general manager. The result is
better models for preclinical testing, he said,
adding that “There is a need in drug discovery for preclinical models that translate into
the human condition better than rodents.”
Organovo’s exVive3D portfolio began
with the recent launch of the exVive3D
Human Liver Tissue for use in
toxicology and other preclinical drug
testing. Additional products are in the
pipeline, with the anticipated release
of the exVive3D Human Kidney Tissue
scheduled for the third quarter of 2016.
CREDIT: ORGANOVO
BY ILENE SCHNEIDER
“Current methods of preclinical using invitro assays in a test tube or in-vivo assays with
animals fall short,” he explains. “Using complex human tissue, we can do experiments
we were never able to do before.”
Organovo, which began in 2007 with technology licensed from the University of Missouri, has compiled validation data over the
past year to research compounds known to
be toxic and drugs that are toxic to the liver.
According to Gallant, “No in-vitro models could
have detected could have detected this data.
This is the only tissue model where researchers
can induce fibrotic disease and detect disease
and toxicity by using human tissues.”
The exVive3D Human Liver Model is created by taking primary cells, putting them
into bio ink and putting them on a 3D printer in spatially controlled matter. As Gallant
explains, “For instance, the liver has three
different cell types. We build a physical piece
of tissue and measure metabolic, genomic
and biochemical endpoints.”
The model “provides an accurate, predictive and reproducible model of human
liver biology for preclinical toxicity testing,”
Gallant adds. At the SOT Annual Meeting,
Organovo, with its 3D bioprinting technology to develop three-dimensional human tissues, is
“a marriage of engineering and biology.” Pictured here is one of its bioprinters in action.
PROTHENA
bind to misfolded forms of the TTR protein but
don’t affect the normal form. The antibodies
interrupt the in-vitro formation of TTR fibrils
and recognize TTR amyloid deposits in cardiac
tissue from ATTR patients. Once bonded to
the misfolded proteins, the antibodies’ ability
to promote the clearance of misfolded TTR
suggests it could have in-vivo potential to
prompt the immune system to remove misfolded TTR amyloid deposits from tissue.
As described in the paper’s abstract, “Antibody clones were generated by immunizing
mice with an antigenic peptide comprising
a cryptotope within the TTR sequence and
screened for specific binding to non-native
Organovo and its pharmaceutical customers—including Bristol-Myers Squibb, Astellas, Merck and L’Oreal—highlighted recent
results that showed how the 3D bioprinted
human liver tissue “effectively models in-vivo
tissue composition and physiology.” The company currently offers the liver model as a service to customers including four of the top 25
global pharmaceutical companies, but hopes
to deliver it as a product, Gallant comments.
According to Dr. Sharon Presnell, Organovo’s chief technology officer and executive
vice president of research and development, “Drug-induced liver injury remains
a major cause of late-stage clinical failures
and market withdrawal, often due to poor
translation from preclinical animal studies
to clinical outcomes. Organovo’s exVive3D
human liver model replicates complex cellcell interactions and key elements of native
tissue architecture to enable the detection of
multiple clinically relevant modes of tissue
injury, including necrosis, immune-mediated
tissue damage, steatosis and fibrosis. When
a preclinical or clinical-stage asset presents a challenging safety or efficacy signal,
exVive3D provides the unique resolving
power of a controlled human tissue microenvironment to investigate mechanism and
develop solutions.”
Organovo’s 3D human tissues have the
“One of the fundamental challenges of developing an
effective treatment for many amyloid diseases, including
ATTR amyloidosis, is creating a therapeutic that not only
reduces circulating levels of the misfolded protein, but
one that can also prevent the formation of new fibrils
and facilitate the elimination of fibrils that have
deposited in tissue and cause progressive organ failure.”
Dr. Gene Kinney, CSO and head of R&D at Prothena
TTR conformations, suppression of in-vitro
TTR fibrillogenesis, promotion of antibodydependent phagocytic uptake of mis-folded
TTR and specific immunolabeling of ATTR
amyloidosis patient-derived tissue.”
Kinney notes that there are no FDAapproved medical treatments for ATTR,
though common unapproved options
“include use of the nonsteroidal anti-inflammatory drug Diflunisal, supportive care that
CREDIT: ORGANOVO
Organovo offers
human tissue with 3D
printing to enable
complex experiments
“There is a need in drug discovery for
preclinical models that translate into the
human condition better than rodents,” says
Paul Gallant, general manager of Organovo, of
his company’s 3D bioprinting technology.
potential to accelerate the drug discovery
process, enabling treatments to be developed faster and at lower cost, according to
Gallant. The exVive3D platform technology
portfolio began with the recent launch of
the exVive3D Human Liver Tissue for use in
toxicology and other preclinical drug testing. Additional products are in the pipeline,
with the anticipated release of the exVive3D
Human Kidney Tissue scheduled for the third
quarter of 2016. n
addresses organ damage and/or, in some
cases, liver transplant. Tafamidis (trade name
Vyndaqel) is approved for use in Europe and
Japan, but not the United States, for the treatment of TTR amyloidosis with polyneuropathy involvement (known as FAP).”
“Antibodies that specifically target the amyloid, such as those described by Prothena, are
not yet in clinical development, but could be
envisioned to be used to directly target amyloid and clear these accumulated forms of the
protein either as a single agent treatment or
in combination with therapies designed to
reduce new production of the TTR protein.
There are no currently approved treatments
that target amyloid to clear the accumulated
forms of TTR,” he adds. n
PRECLINICAL
Mitochondria-based
therapeutics against aging
CohBar announces
preclinical proof-ofprinciple publication for
SHLP mitochondrialderived peptides
MENLO PARK, Calif.—CohBar Inc., a bio-
technology company focused on developing mitochondria-based therapeutics
(MBTs) to treat diseases associated with
aging, announced in mid-April that
researchers at the University of Southern California (USC), in collaboration
with investigators at the Institute for
Aging Research at the Albert Einstein
College of Medicine of Yeshiva University (Einstein), have demonstrated the
ability of small humanin-like peptides
(SHLPs), a novel family of six peptide
hormones discovered by the group, to
regulate metabolism and cell viability in
preclinical studies.
The research, “Naturally Occurring
Mitochondrial-derived Peptides are
Age-dependent Regulators of Apoptosis,
Insulin Sensitivity, and Inflammatory
Markers,” appeared online and in the
May 2016 issue of Aging. CohBar has the
exclusive license for the development of
SHLPs into therapeutics.
SHLPs are encoded in the mitochondria, which are small components of the
cell responsible for converting food into
energy. In the newly published study, the
SHLP hormones demonstrated unique
activities, suggesting therapeutic potential for a number of diseases associated
with aging. Specifically, SHLP2, which
declines with age, has shown characteristics that could be beneficial in the
treatment of Alzheimer’s disease as
well as diabetes, both subjects of ongoing studies by teams at Einstein and
USC. SHLP6 has shown activity in the
promotion of cancer cell apoptosis, a
According to preclinical studies, small humanin-like peptides to regulate metabolism
and cell viability could become a new weapons against many age-related diseases.
mechanism that could be useful in the
treatment of malignancies.
“Together with the previously
described mitochondrial-derived peptides humanin and MOTS-c, the SHLP
family expands our understanding
of the role that these peptides play in
intracellular signaling throughout the
body to regulate both metabolism and
cell survival,” said Dr. Pinchas Cohen,
dean of the USC Leonard Davis School
of Gerontology, founder and director of
CohBar and the senior author on the
study. “These findings further illustrate
the enormous potential that mitochondria-based therapeutics could have on
treating age-associated diseases like
Alzheimer’s and cancer.”
“The preclinical evidence continues
to confirm that these peptides represent a new class of naturally occurring
metabolic regulators,” said CohBar CEO
Simon Allen. “They form the foundation of our pipeline of first-in-class
treatments for age-related diseases, and
we are committed to rapidly advancing
them though preclinical and clinical
activities as we move forward.”
Until recently, according to CohBar,
the mitochondrial genome was believed
to contain only 37 genes and remained
relatively unexplored as a focus of drug
discovery efforts. Research by CohBar
founders and their academic collaborators has revealed that the mitochondrial genome has dozens of potential
new genes that may encode peptides
capable of influencing cellular activities by acting as messengers between
cells, the company adds. In models of
diseases associated with aging, these
peptides have shown disease-modifying
metabolic, neuroprotective, cytoprotective and anti-inflammatory effects. CohBar’s efforts are focused on optimizing
mitochondrial-derived peptides into
MBT drug candidates. MBTs are being
developed for the treatment of diseases
associated with aging, such as obesity,
type 2 diabetes, cancer, atherosclerosis
and neurodegenerative disorders. n
DBV announces data on targeted
regulatory T cell induction during
epicutaneous immunotherapy
MONTROUGE, France—DBV Technologies, a
clinical-stage specialty biopharmaceutical
company, today announced the publication
of experimental data in mice in Cellular &
Molecular Immunology characterizing the
response of regulatory T cell (Tregs) to allergen-specific immunotherapy intended for the
treatment of food allergies.
The study characterized Tregs activity during epicutaneous immunotherapy (EPIT), oral
immunotherapy (OIT) and sublingual immunotherapy (SLIT), and showed that all methods
of treatment desensitized peanut-sensitized
mice, but only EPIT-induced Tregs continued
to show suppressive abilities after treatment
discontinuation.
DBV Technologies is developing Viaskin, a
proprietary technology that uses EPIT to deliver allergenic compounds targeting the immune
system through the immune cells of intact skin,
the Langerhans cells in the epidermis.
“Knowing that maintaining suppression
ability after treatment may lead to the induction of long-term tolerance, we are now working to confirm these experimental data through
our ongoing clinical trials with Viaskin,”
explained Dr. Lucie Mondoulet, deputy chief
scientific officer of DBV Technologies.
The study, “Differences in Phenotype, homing properties and suppressive activities of
Regulatory T cells induced by Epicutaneous,
Oral or Sublingual Immunotherapy in Mice
Sensitized to Peanut,” showed that peanut
desensitization with EPIT, OIT, and SLIT induce
different Tregs subsets with differing homing properties, consequently inducing distinct
long-term efficacy and maintenance ability
in vivo. Tregs observed during OIT and SLIT
showed only an effector/memory cell profile,
while Tregs during EPIT showed both effector/
memory and naive cell profiles. These “naive”
Tregs appear to induce sustained suppression
after discontinuation of treatment, suggesting the induction of a longer-lasting allergen
tolerance in a mouse model. n
SHOW
International
Society for Stem
Cell Research
Moscone Center West San Francisco, California
n
Stem cells in San Francisco
Following a couple of gatherings outside
the United States, ISSCR brings its
annual meeting on stem cell research
to Northern California’s Bay Area
BY JEFFREY BOULEY
SAN FRANCISCO— The Inter-
ers from around the world with
the science most relevant to their
work and foster collaboration that
will drive new breakthroughs and
advances in the field,” says ISSCR
President Dr. Sean J. Morrison.
“The world of stem cells has
changed significantly since 2010,
when the ISSCR last held the
annual meeting in San Francisco,”
he continues. “Meeting attendees
will be treated to a snapshot of the
field and will hear about the most
innovative research in 2016. The
meeting’s plenary sessions will
showcase our basic understanding of stem cell biology and how
we are using that foundation for
understanding disease to create
therapies.”
Opening up the meeting on June
22 at San Francisco’s Moscone Center West will be the Presidential
Symposium, featuring an emphasis
CREDIT: ISSCR
national Society for Stem Cell
Research (ISSCR) is based in the
Greater Chicago area, but it’s done
a good job of living up to the “international” in its name over the years,
with seven of the past 13 annual
meetings taking place outside the
United States—three times in
Canada and also in Sweden, Japan,
Spain and Australia. Now, for the
14th annual meeting, ISSCR 2016
brings the show for a third goround in San Francisco, the site of
its third and eighth meetings.
“There is a great deal of excitement around stem cells in California, and together with our cosponsor, the California Institute for
Regenerative Medicine (CIRM),
we look forward to sharing this
excitement with attendees. The
meeting will connect research-
ISSCR 2016 brings the International Society for
Stem Cell Research’s annual meeting back to San
Francisco for the third time in the event’s 14-year
history. Pictured here is one of the city’s most
iconic landmarks—the Golden Gate Bridge.
Attendees of ISSCR 2015 in Stockholm, Sweden, watch a presentation.
ISSCR 2016 expects to bring together approximately 4,000 stem cell
scientists, bioethicists, clinicians and industry professionals from over 50
countries to present and discuss the latest discoveries and technologies
within the field.
on stem cells and cancer. Speakers
at this symposium will include John
Dick, who is credited with formulating a breakthrough theory of
the role of stem cells in leukemia,
and Pier Paolo Pandolfi, who will
address the issue of the molecular
mechanisms and genetic underpinnings of cancer and targeted
therapeutic strategies coming out
of that.
Other Presidential Symposium
speakers will be Dr. Irving L. Weissman of Stanford University and
Dr. Elaine Fuchs of Rockefeller
University.
The Presidential Symposium will
also include the formal recognition
of the winners of ISSCR’s McEwen
Award for Innovation and an award
lecture presented by Austin Smith,
one of the honorees. Attendees will
hear from the winner of the ISSCR
Dr. Susan Lim Outstanding Young
Investigator Award, and there will
also be the ISSCR Tobias Award
Lecture—new this year—supported by the Tobias Foundation to
recognize original and promising
basic hematology research field as
well as direct translational or clinical research related to cell therapy
in hematological disorders. More
on the awards and awardees can be
found in the article “ISSCR gives
out trio of prestigious awards” on
page 24.
This year, the ISSCR is expanding its scientific program offerings
so that attendees have the opportu-
nity to delve into a greater breadth
of topics. The meeting will include
28 concurrent sessions with 56
invited and 112 abstract-selected
oral presentations. In addition,
three poster sessions will provide
additional opportunities to present and discuss work with fellow
scientists and leaders in the field.
Expanded Focus Session programming on Wednesday morning is organized by different stakeholders to offer an in-depth look at
different aspects of stem cell biology and opportunities in the field,
NEXT YEAR’S EVENT
ISSCR 2017 Annual Meeting
June 14-17, 2017
Boston
Co-sponsored by the Harvard Stem Cell Institute
ISSCR 2016
ISSCR tells DDNews, and it is open
to all registered attendees.
Again this year, ISSCR is offering
a Workshop on Clinical Translation
the day before the meeting, though
separate registration is required for
this event.
In addition to an expanded scientific program, the ISSCR has added
additional networking opportunities: two Attendee Orientations
that help registrants navigate the
meeting and a new Career Fair that
allows attendees to interact with
companies looking to hire in the
stem cell field.
ISSCR notes that its leadership is
always looking for ways to “enhance
the scientific program and maximize opportunities to interact
around the latest breakthroughs
and advances in science,” and notes
that the meeting next year will be
held in Boston, co-sponsored by the
Harvard Stem Cell Institute, with
ISSCR looking forward to drawing
“The meeting will
connect researchers
from around the
world with the
science most relevant
to their work and
foster collaboration
that will drive new
breakthroughs and
advances in the field.”
ISSCR President Dr.
Sean J. Morrison
from the rich scientific backdrop
that Boston offers in terms of academia and industry.
Next year, ISSCR expects to offer
a Physicians Education Program,
which will likely be an independent
event aimed at a clinical audience.
Getting back to this year, though,
Morrison tells DDNews, “The meeting features the most innovative
research in 2016. The plenary sessions showcase our basic understanding of stem cell biology and
how we are using that foundation
for understanding disease to create
therapies.”
One of the plenary sessions at
the meeting, “Cellular Plasticity and Reprogramming,” features
Nobel laureate Shinya Yamanaka of
the Center for iPS Cell Research,
whose work focuses on cell reprogramming. Other plenary sessions
throughout the meeting include
“Tissue Growth and Morphogenesis,” “Gene Networks and
Epigenetics,” “Gene Therapy and
Stem Cells” and “Disease Modeling Using Stem Cells.”
The closing plenary on June 25,
“Cell Therapy in Clinical Trials,”
focuses on the advancement of
stem cell discovery into the clinic
and represents ISSCR’s international breadth with its three
speakers. It features Roger Barker
of the University of Cambridge in
the United Kingdom, whose work
focuses on therapies for neurodegenerative disorders; Koji Eto of
Kyoto University in Japan, who
studies the generation of blood
cells for clinical application; and
Edwin Stone of the University of
Iowa in the United States, whose
focus is the study and treatment of
a wide variety of inherited retinal
diseases.
There is also a symposium for a
public audience called “The Multitalented Stem Cell: Unlocking the
Clinical Potential.” It will highlight
how researchers are developing
cutting-edge stem cell treatments
across a range of disease areas.
All in all, the ISSCR expects to
bring together approximately 4,000
stem cell scientists, bioethicists, clinicians and industry professionals
from over 50 countries to present
and discuss the latest discoveries
and technologies within the field.
“The ISSCR annual meeting is
the definitive international conference for stem cell research, focus-
ing on discoveries and innovations
that are moving the field forward,”
Morrison tells DDNews. “Whether
you are a scientist at the bench,
in industry or in a clinical setting,
the meeting provides invaluable
opportunities to learn and discuss
the science most relevant to your
work. Opportunities to meet and
collaborate with scientists from
around the world can lead to breakthroughs that advance the field for
years to come.” n
CREDIT: ISSCR
Poster sessions like this one from
the 2015 annual meeting provide, as
ISSCR says, “the ultimate
networking experience. Learn more
about research across the breadth
of topics in stem cell science and
present your own research.”
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ISSCR 2016
T
HE ANNOUNCEMENT
about ISSCR’s four
winners for three
awards came out in
February, but the
formal recognition takes place at
ISSCR 2016. Those awards are the
McEwen Award for Innovation,
going jointly to Dr. Austin Smith
of the Wellcome Trust Centre for
Stem Cell Research and Institute for
Stem Cell Biology and Dr. Qi-Long
Ying of the University of Southern
California; the ISSCR Dr. Susan
Lim Outstanding Young Investigator Award, going to Dr. Fernando
Camargo of Boston Children’s Hospital; and the ISSCR Tobias Award
Lecture, which honors Dr. Leonard
Zon of Boston Children’s Hospital.
The McEwen Award for Innovation, supported by the McEwen
Centre for Regenerative Medicine,
recognizes original thinking and
groundbreaking research pertaining to stem cells or regenerative
medicine that opens new avenues
of exploration toward the understanding or treatment of human
disease or affliction. The winner
receives $100,000. Past winners
include Irving Weissman and Hans
Clevers, Azim Surani, James Thomson, Rudolf Jaenisch, and Kazutoshi
Takahashi and Shinya Yamanaka.
According to ISSCR, award recipient Smith has shaped our understanding of embryo stem cell biology
for more than 25 years, and the discoveries of Smith and co-winner Ying
have had important conceptual and
practical impact on stem cell biology.
Smith’s research has largely focused
on embryonic stem (ES) cells and
their relationship to the unspecialized cells resident in the mammalian
embryo that go on to seed the many
tissues and organs of the body.
In 2003, he and Ying showed
that mouse ES cells can be sustained in culture by a specific
combination of growth factors, leukemia inhibitory factor and bone
morphogenetic protein. They proposed that these cytokines act by
inhibiting their differentiation to
specialized cells and, in a landmark
2008 paper, confirmed this hypothesis by using small molecules to
mimic this effect. This research
revealed a “ground state” of pluripotency. These findings enabled
new ES cell lines to be developed
from refractory mouse strains and
paved the way for the extension of
ES cell-directed genetic engineering into the rat, an important tool
for exploring human disease.
ISSCR President Dr. Sean Morrison describes award recipients
Smith and Ying as having “made
enormous contributions to our
fundamental understanding of
pluripotency and how this knowledge can be leveraged to develop
new tools that advance our understanding and treatment of human
disease.”
The ISSCR Dr. Susan Lim Outstanding Young Investigator Award
recognizes exceptional achievements by an ISSCR member and
investigator in the early part of
his or her independent career in
stem cell research. The winner
receives a $15,000 personal award
and an opportunity to present at
the ISSCR Annual Meeting. Past
winners include Paul Tesar, Valentina Greco, Marius Wernig, Cédric
Blanpain, Robert Blelloch, Joanna
Wysocka and Konrad Hochedlinger.
Award recipient Camargo’s
innovative research on adult stem
cells, regulation of organ size and
cancer, together with the development of a paradigm-shifting stem
cell tracking technique, has greatly
CREDIT: ISSCR
ISSCR gives out trio of prestigious awards
The scientific program of ISSCR 2016 has been expanded compared to previous years, with 28 concurrent sessions that
include 56 invited and 112 abstract-selected oral presentations. Pictured here is a panel discussion from ISSCR 2015.
impacted our understanding of
stem cell biology and disease, and
opens new avenues in regenerative
medicine, ISSCR says. His research
on the Hippo signaling pathway
in stem cells has provided a new
understanding of the connection
between the regulation of stem
cells, organ growth and tumorigenesis, with implications for treating
cancer and regenerative disorders.
Camargo’s development of a
novel method of tracking and
monitoring individual blood stem
cells—and their offspring in their
natural environment—opens multiple lines of scientific enquiry
previously not possible, and has
the potential to change our understanding of the blood system and
beyond.
“The ISSCR is delighted to present our Outstanding Young Investigator Award to Fernando Camargo,”
says ISSCR CEO Nancy Witty. “Dr.
Camargo is an innovative young
ISSCR announces RFP for
European co-sponsorship
of the 2021 annual meeting
T
HE ISSCR ANNUAL MEETING is a cornerstone of the society. It provides a core forum
for dissemination of groundbreaking research in all areas of stem cell science and
translation, with participants from academic, industry, ethics and government settings
worldwide. One of the society’s objectives is to choose venues for the annual meeting
that reflect its international character, as well as allowing the ISSCR to highlight the
contributions of the scientific community in the host region.
Currently, the practice is to hold annual meetings at venues outside of North
America every third year and to alternate these meeting sites between Europe and
Asia. The ISSCR board of directors has expressed the desire to hold the annual meeting in Europe in
June 2021 with the support of co-sponsorship from a prominent regional stem cell community. The
board has invited proposals from a local bid committee.
IMPORTANT DEADLINES:
Letter of intent received by July 15, 2016
Full proposals will be received until Oct. 1, 2016
The location will be selected by the board of directors in early 2017
■■
■■
■■
scientist, and we look forward to
watching as his research transforms
our knowledge of stem cell biology,
disease and regeneration and to
involving him in ISSCR leadership
activities.”
This year marks the inaugural
ISSCR Tobias Award Lecture. Supported by the Tobias Foundation,
the award recognizes original
and promising basic hematology research field as well as direct
translational or clinical research
related to cell therapy in hematological disorders. The winner
receives a $15,000 personal award
and presents the Tobias Lecture at
the ISSCR Annual Meeting.
Inaugural award winner Zon
has demonstrated longstanding
scientific leadership in the fields
of hematology, stem cell biology
and zebrafish biology, ISSCR notes,
and he has pioneered the use of
zebrafish for the study of human
blood formation, to identify the
underpinnings of blood disorders
such as leukemia and to find factors that influence blood stem cell
transplantation. To probe blood
stem cell biology in the zebrafish,
he developed many of the techniques that are widely used today,
including transplantation assays
and genetic approaches, providing
the basis of influential discoveries
in the field by himself and others.
His research has also reached into
the clinic, with the discovery and
development of two novel therapeutics that are now being evaluated in clinical trials for patients
with leukemia and melanoma.
“Dr. Zon’s research epitomizes
the bench-to-bedside impact that
we strive for. His research using
zebrafish demonstrates the power
of model organisms to understand
fundamental aspects of hematopoiesis and the ability to translate
those discoveries into new therapies,” says Morrison. n
About the ISSCR
The International Society for Stem Cell Research
is an independent, nonprofit membership organization
established to promote and foster the exchange
and dissemination of information and ideas relating
to stem cells, to encourage the general field of
research involving stem cells and to promote
professional and public education in all areas of stem
cell research and application.
ISSCR 2016 Career Fair
Thursday, June 23
Friday, June 24
9 a.m. to 5 pm.
New this year, attendees can take part in this two-day
event and meet face-to-face with companies looking
to hire for positions within the stem cell community.
The career fair is, ISSCR says, a must-attend for
those seeking career advancement opportunities,
professional development resources and access to
the industry’s top employers.
ISSCR 2016
ISSCR endorses fetal tissue research as essential
research into maternal health, premature births and infant health as
“irreplaceable.” Premature infants
often show delays in neural development, affecting memory, thought
and language. Using fetal brain tissue, researchers have discovered that
the production of new brain cells,
which normally continues throughout fetal development, is impaired
by premature birth. This discovery
makes it possible to explore new
approaches to promote normal
brain cell development in premature
babies. Our understanding of the
causes of retinopathy of prematurity,
a leading cause of blindness in premature infants, has been advanced
by fetal tissue research.
Fetal tissue has also allowed
researchers to test cell-based
approaches to a variety of neuro-
degenerative diseases that do not
have any other effective treatment.
Clinical trials of these fetal tissuederived cells are currently ongoing
for amyotrophic lateral sclerosis
(ALS or Lou Gehrig’s disease),
spinal cord injury, stroke and agerelated macular degeneration.
In closing, fetal tissue research
has led to many new insights into
human development as well as
A MAJOR LEAP FORWARD
Determine the functional impact of genes, proteins,
therapies that have saved millions
of lives. Ongoing access to human
fetal tissue that has been obtained
legally and with donor consent is
required to address many important
questions in biomedical research
and for the development of new
therapies. The ISSCR endorses fetal
tissue research as essential to the
prevention and treatment of lifethreatening diseases. n
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Society for Stem Cell
Research (ISSCR) is
the world’s leading
professional organization of stem cell scientists. The
ISSCR is opposed to recent efforts
to inappropriately limit or prohibit
biomedical research using fetal tissue. These proposals, if enacted,
would obstruct critical biomedical research and inhibit efforts to
improve human health. If enacted
in the past, such limits would have
delayed or prevented the development of therapies that have saved
millions of lives.
Research using donated fetal tissue has been underway since the
1930s and has made major contributions to our understanding of
biology and the development of
new medical technologies. Fetal tissue is obtained from spontaneous
miscarriages and legal abortions. In
each case, the fetal tissue would be
discarded if not donated by patients
for medical research. With the consent of donors, this unique and valuable tissue can be used for research
into basic biological processes and
human development, as well as
creating new treatments for lifethreatening diseases.
Fetal tissue is an essential “goldstandard” resource that enables
laboratory-based research into how
human tissues and organs develop.
While other approaches, such as
using animal models and cells from
adults, can be helpful, for some congenital and developmental conditions it is necessary to study human
fetal tissues. For example, without
fetal tissue research, it would not
be possible to fully understand
congenital defects in the heart or
nervous system, and new therapies
for diseases that affect these tissues
would be delayed or prevented.
Further, some of the most
important fetal tissue research has
involved the use of fetal cell lines in
developing vaccines for many diseases. Millions of lives have been
saved as a result of this research.
The development of the polio vaccine, which relied on the use of
cultured cells from fetal tissue, has
prevented hundreds of thousands of
cases of polio each year and was recognized with a Nobel Prize in 1954.
The April 25, 2014 U.S. Center for
Disease Control and Prevention’s
Morbidity and Mortality Report estimated that as a result of childhood
immunizations, there were 322 million fewer illnesses, 21 million fewer
hospitalizations and 732,000 fewer
deaths among children born in the
United States between 1994 and
2013. A great many of these lives
were saved as the result of research
using fetal tissue.
In addition to their historical
role in vaccine development, the
U.S. National Institutes of Health
recognizes the use of fetal tissue in
Oxygen Consumption Rate (OCR)
T
HE INTERNATIONAL
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Po
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Stressed
Phenotype
Baseline
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Quiescent
Glycolytic
Glycolysis
Extracellular Acidification Rate (ECAR)
ISSCR 2016
Stem Cell Roundup
IN KEEPING WITH THE SUBJECT MATTER OF ISSCR 2016, HERE’S SOME RECENT STEM CELL NEWS
Interim results from
Phase 2 Pathway
study in cervical
spinal cord injury
Researchers at TSRI’s Florida campus say they can now predict how a specific type of stem
cell will act against different diseases.
Scripps Florida scientists
find way to predict
activity of stem cells
Method could help evaluate
potential stem cell therapies
for different diseases
JUPITER, Fla.—Scientists from the Florida
campus of The Scripps Research Institute
(TSRI) have for the first time developed a
way to predict how a specific type of stem
cell will act against different diseases. With
more than 500 stem cell-based therapies
currently in clinical trials, the findings could
have an impact on evaluating these therapies
and developing new ones.
The new study, published recently by the
journal EBioMedicine, was led by Prof. Donald G. Phinney, acting chair of Scripps Florida’s Department of Molecular Therapeutics.
In some respects, stem cells are like
coins—they have two sides. One side is
their shape-shifting ability to differentiate
into other types of cells; the flip side is their
function, the effect they have on health and
disease that underscores their therapeutic
potential. For many years, Phinney noted,
stem cell experts have believed that these
two sides were separate and unrelated.
These new results, however, challenge
that view.
“We found a coordinated link between
stem cell properties and their functions,”
Phinney said. “With this new information,
we can begin to predict how these functions
can be manipulated to make the cells more
therapeutically relevant.”
Using mesenchymal stem cells, Phinney
and his colleagues examined levels of a molecule known as TWIST1 in different human
donor populations. They found higher levels of TWIST1 produced more angiogenic
effects—boosting new blood vessel growth—
while lower levels produced more anti-inflammatory and immuno-suppressive effects.
Moreover, team members were able to show
that manipulating levels of TWIST1 in both
cells and animal models resulted in a predictable change in stem cells’ functional attributes.
Based on their findings, the scientists developed a clinical indications prediction, or CLIP
scale, which predicts the therapeutic potential
of mesenchymal stem cells for a given disease
indication based on their levels of TWIST1.
“There are a number of clinical trials testing mesenchymal stem cells to treat arthritis,” said Siddaraju V. Boregowda, the first
author of the study and a member of the
Phinney lab. “Since angiogenesis is a key
part of the disease process, stem cells with
high levels of TWIST1 (indicating they are
more angiogenic) would not be beneficial.
These cells might be helpful instead for indications such as peripheral vascular disease,
where new vascularization is beneficial. The
proposed CLIP scale accurately predicts
these indications and contra-indications.”
In addition to Phinney and Boregowda,
other authors of “A Clinical Indications Prediction Scale Based on TWIST1 for Human
Mesenchymal Stem Cells” are Veena Krishnappa and Christopher L Haga of TSRI and
Luis A. Ortiz of the University of Pittsburgh. n
company in the research and development
of cell-based therapeutics for the treatment of central nervous system disorders,
announced recently that Dr. Stephen Huhn,
the company’s chief medical officer and vice
president of clinical research, presented
additional details on its ongoing Phase 2
Pathway Study of HuCNS-SC cells (the
company’s proprietary human neural stem
cells) for the treatment of chronic cervical
spinal cord injuries.
The presentation, which took place at
the 2016 American Spinal Injury Association annual meeting in Philadelphia on
April 15, included a top-line update for the
six patients enrolled in open-label Cohort
I from the Pathway Study. The six-month
results from Cohort I showed that muscle
strength had improved in five of the six
patients, with four of these five patients
also demonstrating improved performance
on functional tasks assessing dexterity and
fine motor skills. In addition, four of the
six patients had improvement in the level
of cord injury as measured by International
Standards for Neurological Classification of
Spinal Cord Injury assessment. The company expects to release detailed final 12-month
results on this first open-label cohort later
this quarter.
“The emerging data continue to be very
encouraging,” said Huhn. “We believe that
these types of motor changes will improve
the independence and quality of life of
CREDIT: STEMCELLS INC.
CREDIT: TSRI
NEWARK, Calif.—StemCells Inc., a leading
StemCells Inc. clinicians and scientists
believe that HuCNS-SC cells may have broad
therapeutic application for many diseases
and disorders of the central nervous system.
patients and are the first demonstration that
a cellular therapy has the ability to impact
recovery in chronic spinal cord injury. We
currently have 13 sites in the United States
and Canada that are actively recruiting
patients. We have enrolled and randomized
19 of the 40 total patients in the statistically
powered, single-blind, randomized controlled Cohort II. We are projecting to complete enrollment by the end of September
so that we can have final results in 2017.” n
Pluristem makes patent strides in Japan
CHAIFA, Israel—In mid-April, Pluristem Therapeutics
Inc., a leading developer of placenta-derived cell
therapy products, announced that it has entered into
a licensing agreement with TES Holdings Co. Ltd., a
venture company derived from the University of Tokyo,
to obtain a key patent in Japan to cover the treatment of
ischemic diseases with placental cell therapy rounding
out the company’s intellectual property coverage.
The patent covers use of all placenta-derived
mesenchymal cells that are able to produce VEGF, a
signaling protein that promotes the growth of new
blood vessels, which the body needs to address the
damage in ischemic tissue in the heart, brain, skeletal
muscle, or elsewhere in the body. The patent is valid
through 2023 and may be eligible for up to five years
of patent term extension.
“The University of Tokyo is well known in for its cut-
ting edge research in the field of cell therapy, and we
are happy to expand our cooperation with this world
class academic institution. As we prepare to initiate
a clinical trial in critical limb ischemia targeting conditional marketing approval via Japan’s new accelerated
regulatory pathway for regenerative medicine, our patents addressing placental cell therapies remain a core
asset and important to our current negotiations with
large pharmaceutical companies regarding potential
partnerships in Japan,” stated Pluristem Chairman and
CEO Zami Aberman.
This license news follows Pluristem’s recent
announcement that the Japan Patent Office granted
the company two key patents addressing three-dimensional methods for expanding placental and adipose
cells, and specified cell therapies produced from placental tissue using these methods. n
CLINICAL TRIALS
Global use of ClinCard continues
KING OF PRUSSIA, Pa.—Greenphire, a leader in
clinical payment solutions, reported that it has
issued more than three million patient reimbursements through its ClinCard solution, automating
more than $200 million in payments to clinical
trial participants worldwide. ClinCard provides a
complete audit trail of all global payments while
maintaining blinded patient identities. The ClinCard portal enables reminders for participants
of upcoming trial-related appointments, and the
ClinCard Travel Module helps participants travel
for studies without facing out-of-pocket costs.
“Our ClinCard solution was designed with
the unique perspective that automating patient
reimbursement can bring a significant improvement to the clinical trial experience for everyone
involved—from the sponsor to the patient,” commented Jim Murphy, CEO of Greenphire. “This
focus on optimizing the clinical trial experience
through automated payment solutions has resulted in long-term strategic partnerships with CROs,
sponsors and research sites around the world.”
WCG forms advisory board for
gene therapy research
PRINCETON, N.J.—WIRB-Copernicus Group (WCG)
Prader-Willi progress Depression
deterrent
Pivotal Phase 3 study
examines safety and efficacy
of novel obesity therapeutic
Minerva-Janssen joint
development drug for
MDD gets high marks
in clinical trials
BY JIM CIRIGLIANO
BOSTON—Biopharmaceutical company Zaf-
gen Inc. in April announced new data from
its bestPWS ZAF-311 study—a pivotal, double-blind, placebo-controlled Phase 3 trial
evaluating the safety and efficacy of the company’s lead product candidate beloranib—in
patients with Prader-Willi syndrome (PWS)
during the six-month randomized treatment
period. Beloranib, a MetAP2 inhibitor, is a
novel, first-in-class, twice-weekly subcutaneous injection being developed for the
treatment of multiple indications, including severe obesity in PWS; obesity caused
by hypothalamic injury, including craniopharyngioma-associated obesity; and severe
obesity in the general population.
In the bestPWS ZAF-311 study, patients
received twice-weekly subcutaneous injections of either 2.4 mg or 1.8 mg of beloranib
or placebo. The trial included patients whose
average age was 20 years. Patients in the
trial were markedly obese at baseline; at the
CREDIT: NASDAQ
BRIEFS
Zafgen is developing beloranib, a MetAP2
inhibitor, as a novel, first-in-class, twice-weekly
subcutaneous injection for severe obesity in
PWS, obesity caused by hypothalamic injury
and severe obesity in the general population.
Pictured here are Zafgen representatives at the
closing bell of NASDAQ in 2014, shortly after
the company’s initial public offering.
beginning of randomized treatment, patients
had an average BMI of 40 kg/m2, an average
body weight of 100 kg, an average fat mass of
51 kg and an average hyperphagia total score
of 16.9 (consistent with moderate to severe
hyperphagia).
ZAFGEN CONTINUED ON PAGE 28
CREDIT: BIOLINERX
recently convened the WCG Gene Therapy Advisory Board to advise the company on the latest
advances in gene therapy research. The board will
offer guidance and strategic counsel for WCG’s
oversight of human gene transfer research, which
involves coordinating institutional review board
and institutional biosafety committee reviews. In
addition, this group will also aid WCG in prepping
clients to manage increasing volumes of gene
therapy research.
IN THIS SECTION
Early trial info/Trial starts
Out of the starting gate........................... 30
Depression/Insomnia
Depression deterrent............................... 27
Diabetes
Insulin with the quickness
(LISPRO from cover)................................. 31
Infectious disease
Genocea shares data on
GEN-003 for genital herpes..................... 28
Genomics
WCG forms advisory board
for gene therapy research....................... 27
Obesity/Metabolic
Prader-Willi progress............................... 27
Oncology
BL-8040 clears Phase 2 safety trial......... 27
Trial reimbursement
Global use of ClinCard continues............ 27
In addition to the AML study just reported on, BioLineRx in March announced the initiation of a
Phase 2 trial for BL-8040 as a novel approach for the mobilization and collection of bone
marrow stem cells from peripheral blood circulation.
BL-8040 clears
Phase 2 safety trial
BioLineRx shares topline results for its AML
drug candidate
BY LORI LESKO
TEL AVIV, Israel—Aimed at developing an
effective treatment—and eventual cure—
for relapsed or refractory acute myeloid
leukemia (r/r AML), a cancer of the blood
and bone marrow, clinical-stage biopharma-
BY ILENE SCHNEIDER
WALTHAM, Mass.—Minerva Neurosciences Inc. achieved positive top-line
results in a Phase 1b clinical trial in
major depressive disorder (MDD)
with MIN-202 (JNJ-42847922). The
selective orexin-2 receptor antagonist
is under joint development between
Minerva and Janssen Pharmaceutica
NV. A clinical-stage biopharmaceutical company that develops therapies
for central nervous system (CNS)
disorders, Minerva’s proprietary compounds include: MIN-101, in Phase 2b
development for schizophrenia; MIN202 (JNJ-42847922), in Phase 2a and
“Treatment with MIN202 was observed to
result in consistent
improvements in the
symptoms of depression
in MDD patients in
this trial ... These
improvements support
the potential of MIN-202
to have a direct effect on
mood independent from
its effect on sleep.”
Dr. Remy Luthringer,
president and
CEO of Minerva
ceutical BioLineRx has reported successful
positive top-line results following the Phase
2 clinical trial of the drug BL-8040. Detailed
results will be presented at an upcoming scientific conference.
Approximately 19,000 new cases of AML
were diagnosed in the United States in 2014,
with the median age of onset at 67, according to the American Cancer Society. The
first treatment line for patients with AML
Phase 1b development for insomnia
and adjunctive treatment of MDD,
respectively; MIN-117, in Phase 2a
development for MDD; and MIN-301,
in preclinical development for Parkinson’s disease.
According to Dr. Remy Luthringer,
president and CEO of Minerva, “Treatment with MIN-202 was observed to
result in consistent improvements in
the symptoms of depression in MDD
patients in this trial. The results pave
the way to initiate a Phase 2b trial in
patients suffering from MDD. These
improvements support the potential
of MIN-202 to have a direct effect on
mood independent from its effect on
BL-8040 CONTINUED ON PAGE 29
MIN-202 CONTINUED ON PAGE 30
CLINICAL TRIALS
Genocea shares data on GEN-003 for genital herpes
Immunotherapy shows
sustained reduction of viral
shedding rate and durable
impact on clinical disease 12
months post-dosing
CAMBRIDGE, Mass.—Genocea Biosciences
Inc., a biopharmaceutical company developing T cell-directed vaccines and immunotherapies, announced recently positive
12-month efficacy data from its Phase 2 dose
optimization trial evaluating GEN-003 for
the treatment of genital herpes.
GEN-003 demonstrated sustained and
statistically significant reductions compared to baseline in the rate of viral shedding 12 months after dosing across multiple
dose groups, as well as sustained efficacy at
multiple dose levels across secondary endpoints measuring the impact on clinical disease. GEN-003 was safe and well tolerated
by patients, with no serious adverse events
related to the vaccine in the trial.
“We are very pleased with these data,
which show that GEN-003 has strong and
durable effects on both HSV-2 viral activity
and genital herpes clinical disease, supporting our belief that GEN-003 could become a
cornerstone treatment for patients affected
ZAFGEN
Of the 107 patients in the study, 74 completed the full 26-week treatment per the
study protocol, and 27 patients completed
at least 75 percent of the treatment period
prior to the suspension of dosing in the trial
in October 2015.
The trial had two primary efficacy endpoints: improvement in hyperphagia-related behaviors and reduction in body weight.
Patients treated with both the 1.8 mg and
2.4 mg doses of beloranib demonstrated a
significant reduction in total body mass and
fat mass, with approximately 90 percent of
the total body mass lost being from body fat
reduction, indicating preferential loss of fat
rather than lean mass.
The control group of patients receiving
placebo experienced a substantial (4.15
percent) increase in body weight over the
six-month course of randomized treatment,
which is expected in this patient population that typically experiences weight gain
throughout life without effective treatment
for managing obesity. By contrast, patients
treated with beloranib experienced a reduction in weight as high as a 5.3-percent reduction from baseline in the group treated with
the larger (2.4 mg beoranib) dosage, with a
placebo-adjusted weight loss of 9.45 percent.
Secondary endpoints in the study included improvement in total body fat mass and
improvement in lipids and markers of cardiometabolic risk (TC and LDL). The results
showed beloranib to be associated with
improvements in total and LDL cholesterol
and with the other markers of cardiometabolic risk, compared to placebo, while the
mean change in HDL cholesterol and triglycerides showed no significant change
from baseline for each treatment group.
The reduction in leptin levels and increase
in adiponectin levels observed in patients
at both beloranib dosages in the study are
by this serious disease. Specifically, a single
course of treatment of GEN-003 may offer
benefits similar to a full year of daily administration of oral antivirals—but with greatly
improved convenience,” said Chip Clark,
president and CEO of Genocea. “We anticipate reporting virologic efficacy data for
GEN-003 from our recently initiated Phase
2b study in the third quarter of 2016, clinical efficacy data at six months post-dosing
around the end of 2016 and conducting our
end of Phase 2 meeting with the FDA in the
first quarter of 2017.”
“These 12-month data highlight the potential of GEN-003 to significantly enhance the
genital herpes treatment landscape,” said
Dr. Lori A. Panther, an infectious diseases
specialist at Beth Israel Deaconess Medical
Center and assistant professor of medicine
at Harvard Medical School. “Because of the
physical and psychological impact of this disease, both patients and treating physicians
would be eager to use an effective treatment
that more conveniently improves control of
outbreaks. The reduction in viral shedding,
which is thought to cause the epidemic
spread of genital herpes, is also encouraging.”
This Phase 2 study enrolled 310 subjects
from 17 institutions in the United States. Subjects were randomized to one of six dosing
consistent with altered fatty acid mobilization and lipid utilization.
At the end of the randomized treatment
period, there were no clinically significant
abnormal patterns regarding laboratory
values, vital signs or electrocardiography
findings. Six patients in the study, however,
withdrew due to adverse effects; a total of
five serious adverse events were reported
during the trial. The most common adverse
events encountered during the study were
injection site bruising, aggression and
hyperphagia; these occurrences were generally mild and temporary. Of these, only
injection site bruising was reported notably
more frequently in patients taking beloranib
compared to placebo.
Serious adverse events that occurred during the study include aggression (placebo,
2.4 mg beloranib), ankle fracture (placebo),
mental status change (1.8 mg beloranib) and
pulmonary embolism (1.8 mg beloranib). The
study’s authors note, however, that many of
these—specifically psychiatric disorders—
are commonly observed as background
comorbidities in PWS patients.
Zafgen has previously disclosed an association of venous thromboembolic events
reported in patients treated with beloranib
vs. placebo, including one fatal case of pulmonary embolism (1.8 mg beloranib) during the randomized portion of the bestPWS
study that was reported in October 2015. No
other venous thromboembolic events were
reported during the blinded randomized
portion of the bestPWS study. Also previously reported was a second patient death
associated with pulmonary embolism (2.4
mg beloranib) and two cases of deep vein
thrombosis (1.8 mg and 2.4 mg beloranib),
which occurred during the open-label extension portion of the bestPWS study; no other
deaths have occurred over the course of the
beloranib program.
“The ZAF-311 study demonstrated that
beloranib has a clear efficacy benefit in PWS
“These 12-month data
highlight the potential of
GEN-003 to significantly
enhance the genital herpes
treatment landscape.”
Dr. Lori A. Panther of
Harvard Medical School
groups of either 30 µg or 60 µg per protein
paired with one of three adjuvant doses (25
µg, 50 µg or 75 µg). A seventh group received
placebo. Subjects received three doses of
GEN-003 or placebo at 21-day intervals.
Baseline viral shedding and genital lesion
rates were established for each subject in a
28-day observation period prior to the commencement of dosing by collecting 56 genital
swab samples (two per day), which were analyzed for the presence of HSV-2 DNA, and by
recording the days on which genital lesions
were present.
This 28-day observation period was repeated
immediately after the completion of dosing
and at six and 12 months following dosing.
No booster doses were given. After the 28-day
observation period immediately following dosing, patients in the placebo arm were rolled
Zafgen has previously disclosed an
association of venous thromboembolic events
reported in patients treated with beloranib vs.
placebo and is trying to better understand the
benefit/risk relationship of beloranib to
develop a strategy for risk mitigation.
patients,” says Dr. Thomas Hughes, CEO of
Zafgen. “We are actively working to better
understand the mechanisms and incidence of
underlying thromboembolic disease in PWS,
as well as the potential impact of beloranib
treatment on thrombosis in order to better
understand the benefit/risk relationship of
beloranib and develop a strategy for risk mitigation in this high-risk patient population.”
In an effort to resolve the full clinical
hold the FDA placed on the beloranib IND
in December 2015, Zafgen plans to present
the data from the ZAF-311 clinical trial, along
with previously reported data from the ZAF203 Phase 2b clinical trial of beloranib in obesity complicated by type 2 diabetes, as well as
a proposal for a risk-mitigation strategy for
beloranib in PWS.
“We look forward to identifying a path forward for beloranib in PWS and providing an
update from our discussions with the FDA,”
says Hughes.
In other recent PWS news unrelated to
Zafgen, Lyon, France-based Alizé Pharma
SAS, an Alizé Pharma group company specialized in the development of biopharmaceuticals to treat metabolic disorders and
rare diseases, announced top-line results of
a Phase 2 clinical trial of AZP-531, its unacylated ghrelin analog, in patients with PWS.
This randomized, double-blind, placebocontrolled, European multicenter study was
aimed at evaluating the safety, tolerability
and efficacy of AZP-531 administered daily
subcutaneously for 14 days on food-related
behavior vs. placebo. The trial was conducted
over across the six active combinations of GEN003 and Matrix-M2 under a separate protocol.
GEN-003 is a first-in-class T cell-directed immunotherapy designed to elicit both
a T cell and B cell immune response. The
immunotherapy was designed using Genocea’s ATLAS platform, which profiles the
comprehensive spectrum of actual T cell
responses mounted by humans in response
to disease, to identify antigen targets that
drive T cell response. GEN-003 includes the
antigens ICP4 and gD2 along with MatrixM2TM adjuvant, which Genocea licenses
from Novavax Inc.
Genital herpes affects more than 400 million people worldwide and causes recurrent,
painful genital lesions. It can be transmitted
to sexual partners, even when the disease is
asymptomatic. Current genital herpes therapies only partially control clinical symptoms
and viral shedding, a process which drives
disease transmission. Incomplete control of
genital lesions and transmission risk, expense
and the perceived inconvenience of taking a
daily medication are hurdles for long-term
disease management. Immunity through T
cells is believed to be particularly critical to
the control and possible prevention of genital
herpes infections. n
across seven centers in France, Spain and
Italy. It enrolled a total of 47 patients with
genetically diagnosed PWS and evidence of
hyperphagia.
The results showed a significant improvement in food-related behavior in patients
treated with AZP-531, as assessed by the
Hyperphagia Questionnaire (HQ), the most
widely used tool for assessing efficacy in
clinical trials in PWS. The results showed
a particular improvement in the Hyperphagic Severity domain score of the HQ. These
findings were supported by a reduction in
appetite following breakfast for patients
treated with AZP-531, as assessed by a newly
developed patient-reported outcome scale.
Glucose control improved with AZP-531
treatment, with a greater effect observed in
patients with higher fasting or postprandial
glucose levels at baseline. Body weight did
not change significantly in either group,
which is not unexpected following shortterm treatment in a study population with
a highly variable weight. However, a significant reduction in waist circumference
was noted in the AZP-531 group, which
was not observed in the placebo group.
AZP-531 was well tolerated with no serious
or severe adverse events and no clinically
significant changes with respect to safety
laboratory tests.
“Hyperphagia is a devastating feature of
Prader-Willi syndrome as it dramatically
impairs the quality of life of the patients and
their families and may also lead to morbid
obesity and related cardiovascular complications. In this regard, the impact of AZP-531
on food-related behavior in this trial is clinically relevant, highly promising and calls for
the implementation of longer-term clinical
trials,” said Prof Maïthé Tauber, a pediatric
endocrinologist at the Hospital of Toulouse,
coordinator of the Reference Center for Prader-Willi Syndrome in France and the coordinating principal investigator of the study. n
S
R
R
CLINICAL TRIALS
BL-8040
includes a combination of chemotherapy
drugs, rendering patients weak and sick and
significantly impacting their quality of life.
Scientists discovered that patients’ median
outcome after chemo was less than two years.
However, the addition of BL-8040 to the
treatment resulted in another story.
The Phase 2 trial was a multicenter, openlabel study to assess safety, efficacy pharmacodynamics and pharmacokinetic parameters of
BL-8040 in combination with Cytarabine (AraC) for the treatment of adult r/r AML patients.
Forty-two patients with r/r AML were enrolled
in the study, which included a dose-escalation
stage followed by an expansion stage. Each
patient received a once-daily dose of BL-8040
monotherapy on days one and two, followed by
the same dose of BL-8040 plus Ara-C on days
three to seven. Clinical response to treatment
was evaluated by bone marrow biopsy on day
30. Results indicated that BL-8040, as a single
agent and in combination with Ara-C, was safe
and well tolerated at all doses tested, up to and
including the highest dose level of 2 mg/kg,
with no major adverse events.
“We are very enthusiastic about the
positive results from the Phase 2 trial with
BL-8040 for the treatment of relapsed or
refractory AML,” Dr. Kinneret Savitsky,
CEO of BioLineRx, stated in a press release.
“We are especially excited that for the first
time, we see a direct correlation between
clinical response and a specific subset of the
study patient population. Given that AML
is a heterogeneous disease, the ability to
predefine the population that may benefit
CREDIT: BIOLINERX
Recent trial results suggest that BioLineRx’s BL-8040 for AML significantly induces mobilization
of leukemic cells from the protective microenvironment of the bone marrow into the peripheral
blood and also directly leads to apoptosis of leukemic progenitor cells. Leukemic stem cells are
thought to be a major reason for AML relapse.
from CXCR4 inhibition is very important
for future development.”
“The majority of high-risk AML patients
achieved first complete remission relapse
within one year, despite the current standard consolidation therapy,” Savitsky added.
“Patients with AML relapse have a poor
prognosis despite further therapy, and less
than 10 percent of these patients are cured
by conventional therapy.”
The results showed that BL-8040 “not
only significantly induces mobilization of
leukemic cells from the protective microenvironment of the bone marrow into the
peripheral blood, but also directly leads to
apoptosis of leukemic progenitor cells and
triggers terminal differentiation of the cells
into granulocytes,” he said.
Leukemic stem cells that are “dormant in
Smart assays KNOW INDIGO!
the bone marrow are presumed to be a major
reason for AML relapse,” Savitsky noted.
“Based on the preclinical and clinical data
accumulated to date, BL-8040 is anticipated
to boost the efficacy of consolidation therapy
due to its dual mechanism of action,” which
first “induces mobilization of leukemic cells
from the bone marrow, which enhances the
cytotoxic effects of chemotherapy, and secondly, it possesses antileukemic pro-apoptotic properties that help eliminate AML cells
directly.”
“Combined with the impressive remission rate reported from subjects receiving
BL-8040 doses of 1 mg/kg or higher, the
results strongly suggest that BL-8040 has
potent antileukemic activity and, in combination with Cytarabine, may improve the
response typically achieved in this advanced
AML population,” he remarked. “These successful results also reinforce our excitement
about BL-8040’s overall potential in the AML
space, including as an AML consolidation
treatment that is currently being investigated
in a large Phase 2b study at approximately
25 sites in Germany. Given these positive
results, we now plan to meet with the regulatory authorities to discuss the next steps in
the development of this promising program.”
Dr. Arnon Aharon, vice president of Medical Affairs at BioLineRx, tells DDNews, “With
regard to the durability of the response to
treatment, we are following our patients for
overall survival (OS) and will publish that
data once we complete the patients’ followup. We plan to continue development
of BL-8040 for the treatment of AML, with
an emphasis on the consolidation treatment
line for which we are currently conducting
a Phase 2b trial. In addition, we recently
entered into an immuno-oncology collaboration with Merck under which we plan to
initiate a Phase 2 clinical study to investigate
BL-8040 in combination with Keytruda for
the treatment of pancreative cancer.”
On March 23, BioLineRx announced the
initiation of a Phase 2 trial for BL-8040 as
a novel approach for the mobilization and
collection of bone marrow stem cells from
peripheral blood circulation. The study
will be conducted in collaboration with the
Washington University School of Medicine
Division of Oncology and Hematology, and is
designed to evaluate the ability of BL-8040 as
a single agent to promote stem cell mobilization for allogeneic transplantation. n
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CLINICAL TRIALS
OUT OF THE STARTING GATE
A roundup of clinical
trial startups and initial
breakthroughs
BY JEFFREY BOULEY
BURLINGTON, Mass.—Flexion Therapeutics
Inc. in late April reported it had enrolled the
first patient in a clinical trial to assess the
effects of its lead drug candidate, Zilretta
(FX006), on blood glucose levels in approximately 36 adults with osteoarthritis (OA)
of the knee who also have type 2 diabetes.
“This clinical trial in patients with OA
of the knee will assess whether Zilretta, an
investigational intra-articular sustainedrelease steroid (triamcinolone acetonide,
or TCA) treatment, can avoid the substantial elevations in blood glucose levels that
often occur in diabetic patients treated with
immediate-release TCA,” said Dr. Michael
Clayman, Flexion Therapeutics’ president
and CEO. “Following an IA injection of
immediate-release TCA, plasma concentrations of TCA rise rapidly to levels that may
cause hyperglycemia in this patient population. Because peak plasma concentrations
after a Zilretta injection, as demonstrated
in clinical trials, are more than an order
of magnitude lower than with immediaterelease TCA, we believe it’s reasonable to
expect that injections of Zilretta may avoid
these increases in blood sugar. If the data
support this expectation, Zilretta could
confer an important safety advantage for
the 750,000 people in the U.S. with knee
OA who have diabetes and receive IA corticosteroid injections annually.”
Zilretta was designed using proprietary
microsphere technology and is intended to
provide localized and long-lasting pain relief
over a period of months while minimizing
systemic exposure and avoiding serious side
effects common to oral therapies prescribed
for OA pain.
Following is news of other companies
reporting trial starts and very early trial
information:
Loxo Oncology announces first
pediatric response to LOXO-101
STAMFORD, Conn.—Loxo Oncology Inc., a
biopharmaceutical company innovating the
development of highly selective medicines
for patients with genetically defined cancers,
in mid-April announced the publication of
a manuscript in the online edition of the
journal Pediatric Blood and Cancer describing a confirmed RECIST partial response
in the first patient enrolled in the recently
opened pediatric Phase 1 dose-escalation
trial of LOXO-101.
The peer-reviewed manuscript describes a
16-month old female patient with advanced
infantile fibrosarcoma (IFS), a rare pediatric
cancer. Genetic testing revealed an ETV6NTRK3 fusion, which is frequently found
in IFS. Following multiple unsuccessful
surgeries and courses of chemotherapy, the
patient was enrolled in the pediatric Phase
1 trial of LOXO-101, which employs a liquid
formulation of the drug designed specifically for pediatric patients unable to swallow capsules.
“Most infants and children with infantile
fibrosarcoma can be cured through surgery
and chemotherapy. When our patient’s disease progressed in spite of these treatments,
the only other viable treatment option was
radiation therapy, which posed devastating
long-term consequences for our patient,”
said Dr. Ramamoorthy Nagasubramanian,
first author of the manuscript and division
chief of pediatric hematology-oncology at
Nemours Children’s Hospital, as well as an
assistant professor of pediatrics at the University of Central Florida College of Medicine.
“The rapid, dramatic reduction in tumor size
shows early but promising evidence of the
potential for LOXO-101 to provide signifi-
MIN-202
cant benefit for pediatric patients harboring
NTRK gene fusions.”
Phase 3 trial of enzalutamide initiated in
hormone-sensitive prostate cancer
SAN FRANCISCO & TOKYO—Medivation
Inc. and Astellas Pharma Inc. in late March
announced that the ARCHES Phase 3 registrational trial, which will evaluate the efficacy and safety of enzalutamide with androgen deprivation therapy (ADT) vs. placebo
with ADT in metastatic hormone-sensitive
prostate cancer (mHSPC) patients, has
been initiated and the first patient has been
randomized.
Androgen deprivation therapy, which
reduces the levels of male hormones, is the
standard of care for patients with mHSPC.
The ARCHES trial will investigate whether
the addition of enzalutamide to ADT may
benefit this patient population compared to
ADT alone.
Celldex initiates Phase 1/2 study
of glembatumumab vedotin
HAMPTON, N.J.—Celldex Therapeutics Inc.
announced April 12 that it had initiated an
open-label Phase 1/2 safety and tolerability
study of glembatumumab vedotin in patients
with unresectable stage IIIB or IV, gpNMBexpressing, advanced or metastatic squamous cell carcinoma (SCC) of the lung, who
have progressed on prior platinum-based
chemotherapy.
Glembatumumab vedotin is a fully human
monoclonal antibody-drug conjugate (ADC)
that targets gpNMB, a protein overexpressed
by multiple tumor types, including SCC of
MIN-202, a selective orexin-2
receptor antagonist under joint
development between Minerva
and Janssen Pharmaceutica,
recently showed promise in a
Phase 1b clinical trial in major
depressive disorder.
sleep. We previously observed that MIN-202
had a significant effect on sleep in our Phase
2a trial in patients suffering from insomnia
disorder.”
MIN-202 seeks to inhibit the activity
of the neurons that promote wakefulness
by selectively blocking the orexin 2 receptor. The orexin system is involved in the
control of several key functions, including
metabolism and wakefulness. Blocking the
orexin 2 receptor reduces the level of neurotransmitter traffic that signals the brain to
maintain vigilance and wakefulness, which
can be helpful for patients with insomnia.
This is a completely different mechanism
from products that work as GABA (gammaaminobutyric acid) agonists, which induce
sleep via sedation.
Minerva entered into a co-development
and license agreement with Janssen in February 2014 that covered MIN-202 and any
other orexin 2 compounds. Under this agreement, Minerva has an exclusive license to
these compounds in the European Union,
Switzerland, Liechtenstein, Iceland and
Norway, while Janssen has exclusive rights
to these compounds worldwide outside of
those territories. During its 2015 Pharma-
“Zilretta could confer an important safety advantage for
the 750,000 people with knee OA who have diabetes and
receive IA corticosteroid injections annually.”
Dr. Michael Clayman, president and CEO of Flexion
ceutical Pipeline update, Janssen reported
that it plans to file the insomnia disorder
indication by 2019.
According to the company, the Phase 1b
trial was a randomized, multicenter, doubleblind, parallel group, diphenhydramine- and
placebo-controlled study to evaluate the
effect of MIN-202 in MDD outpatients 18
to 65 years of age. Forty-eight participants
were enrolled in three groups that received
doses of 20 mg of MIN-202 daily, 25 mg of
diphenhydramine daily (used as a positive
control to induce sedation) or placebo over
four weeks. MIN-202 was well tolerated by
study participants over a one-month treatment period, with no new safety problems
or adverse events.
There were consistently greater improve-
the lung, where approximately 85 percent of
patients overexpress the marker.
“While checkpoint inhibitor therapy has
been an important development for patients
with squamous cell lung cancer, the majority of patients still require new, effective
treatment options—especially targeted
therapies,” said Dr. Thomas Davis, executive
vice president and chief medical officer of
Celldex. “gpNMB, the target of glembatumumab vedotin, is strongly expressed in the
vast majority of squamous cell lung cancers.
Glembatumumab vedotin has consistently
induced notable response rates in other
difficult-to-treat cancers that overexpress
gpNMB. We hope to elicit similar activity in
squamous cell carcinoma and look forward
to completing this study.”
Inovio partners will begin hepatitis C trial
PLYMOUTH MEETING, Pa.—Inovio Pharmaceuticals Inc. announced recently its
immunotherapy for hepatitis C (INO-8000)
will be evaluated in a Phase 1 trial in chronically infected patients who are not receiving
other hepatitis C virus (HCV) treatments.
The study will enroll patients who are in
the early stages of chronic HCV infection to
determine the therapy’s ability to decrease
and potentially eliminate HCV viral load,
measure HCV-specific immune responses
and durability of these immune responses,
and evaluate safety and tolerability. In this
dose-escalation study INO-8000 will be combined with increasing doses of DNA-based
IL-12 (INO-9012), an immune activator,
which in previous studies has been shown
START CONTINUED ON PAGE 31
ments in depressive symptomatology in
patients randomized to receive MIN-202, as
compared with those randomized to receive
placebo or diphenhydramine. These were
measured by clinician-administered rating
scales, including the Hamilton Depression
Rating Scale (HDRS17). Core symptoms of
depression (as measured by the HAM-D6)
were significantly improved in the MIN-202
arm when compared with the placebo arm.
The primary endpoint was safety and tolerability, and secondary endpoints included
assessments of depressive symptomatology,
cognition and sleep. The trial was conducted
at seven clinical sites in Europe.
MIN-202 is also under development to
treat primary insomnia disorder. Top-line
data from a Phase 2a trial in this indication
included statistically significant improvements in sleep efficiency as measured by
objective polysomnography, the primary
endpoint of the trial. This was observed in
study patients treated with MIN-202, with
an acceptable safety and tolerability profile,
compared to patients treated with placebo.
“It is premature to discuss the commercial
potential of this product,” Luthringer commented. “Such potential will be defined significantly by data from advanced clinical trials
in insomnia disorder and mood disorders.” n
CLINICAL TRIALS
LISPRO
significant 22-percent reduction in
blood glucose excursion over the first
two hours compared to Humalog. The
pharmacokinetic profile of BioChaperone Lispro U100 was consistent
with that observed in previous studies in people with T1D, demonstrating
a statistically significant 83-percent
increase in exposure to insulin lispro
over the first 30 minutes compared to
Humalog.
“We are encouraged by the results of
this trial,” said Dr. Thomas Hardy, senior
medical director of endocrinology at
Lilly. “In addition, we are pleased with
the expeditious progress of our joint
program with Adocia.”
Just a little over a month before, the
two companies had announced positive
topline results from a Phase 1b clinical
trial for BioChaperone Lispro, which
was the first outpatient 14-day study
comparing the effect of multiple daily
injections of BioChaperone Lispro and
Humalog on postprandial glycemic control relative to solid standardized meals
in 36 patients with T1D.
At the beginning of the study, when
injected at the time of meal, BioChaperone Lispro demonstrated a statistically
significant 31-percent reduction in blood
glucose excursion over the first two hours
compared to Humalog. After 14 days of
treatment for each treatment, BioChaperone Lispro also demonstrated a statistically significant 42-percent reduction
in blood glucose excursion over the first
two hours compared to Humalog, when
injected at the time of the meal. This last
result demonstrates the robustness of the
performance of BioChaperone Lispro on
a two-week period.
“This was an important study and
provides our first experience with repeat
doses of this ultra-rapid insulin formulation in an outpatient setting,” said
Hardy. “We are encouraged by these
results and look forward to seeing the
results of additional, ongoing studies.”
In the T2D and the T1D studies, both
BioChaperone Lispro and Humalog
were similarly well tolerated throughout the 14 days. No new or unexpected
safety findings were observed and no
local reactions were seen on the site of
administration for either treatment.
The news regarding BioChaparone
Lispro could be a particularly good thing,
given some weakness on the Humalog
START
to increase the therapeutic immune
response to DNA immunotherapies.
ABIVAX cleared in Spain for
Phase 2a clinical trial of ABX464
PARIS—ABIVAX announced in April
that its second Phase 2a study with
ABX464, a first-in-class drug candidate
for the treatment of patients with HIV/
AIDS, has been approved by regulatory
and ethics committees in Spain. Additional approvals in Belgium and France
are expected in the near future.
ABX464 is an orally available smallmolecule therapeutic candidate that is
currently in mid-stage clinical testing
CREDIT: ADOCIA
Adocia’s BioChaparone technology is designed to accelerate insulin absorption, and
has shown its mettle in allowing BioChaperone Lispro to beat out Lilly’s Humalog for
speed and effectiveness—a big reason why Lilly is partnered with Adocia in
developing BioChaperone Lispro.
front. In analyzing Lilly’s recent Q1
financial report, Leerink Partners noted
that total revenue of $4.87 billion was in
line with consensus ($4.84 billion), but
$125 million below Leerink’s forecast
($4.99 billion), with Seamus Fernandez
and colleagues at Leerink writing: “The
biggest surprise in sales figure was a significant drop in Humalog sales ($606
million vs. consensus $722 million and
Leerink estimate of $745 million).”
Not that Lilly is doing bad on the
diabetes front, Leerink noted. Sales of
Trulicity (a once-weekly GLP 1 for T2D
that helps activate the body’s ability to
release its own insulin) “came in $34
million above our forecast, and this
agent is tracking to become a blockbuster product.” In addition, Jardiance (an
oral T2D medicine that helps control
blood sugar levels by helping the kidneys
get rid of glucose from the bloodstream)
sales “beat our estimate by $13 million,
which is encouraging.”
Leerink also acknowledged that Lilly’s
profitability “was clearly dragged down
by government rebate volatility, which
significantly dragged down Humalog
growth.”
The Adocia-Lilly story has had its own
ups and downs over the years. Lilly made
a deal with Adocia in 2011 to co-develop
a rapid-uptake insulin, and then about
18 months later, despite a successful
Phase 1 trial, Lilly walked away from
the deal without any real explanation.
Forging ahead on its own, Adocia turned
that insulin into what became known
as BioChaperone Lispro and showed in
a Phase 2a study that the insulin took
effect faster than Lilly’s Humalog.
So, in 2014, Lilly came back to the
table with a collaboration deal worth
up to $570 million, under which Lilly
would pay its French partner $50 million up front for the exclusive rights
to BioChaperone Lispro, which is a
synthetic insulin tied to Adocia’s proprietary delivery system, plus $280
million more in payments attached to
development and regulatory milestones
and another $240 million contingent on
product sales. n
in HIV patients. It works by inhibiting
HIV replication through a novel mechanism (i.e. the modulation of RNA splicing) that may not be vulnerable to the
development of resistance by the HIV
virus, and may have a sustained effect
in patients.
failure and reduced ejection fraction.
Omecamtiv mecarbil, a novel investigational cardiac myosin activator that
increases cardiac contractility, is being
developed by Amgen in collaboration
with Cytokinetics for the potential treatment of heart failure.
“Advancing the clinical investigation
of omecamtiv mecarbil in Japan represents an important step for our novel
cardiac myosin activator program,” said
Dr. Fady I. Malik, Cytokinetics’ executive vice president of research and development. “Omecamtiv mecarbil holds
promise as a potential new treatment
for patients with heart failure, and we
look forward to learning about its clinical application in Japanese patients.” n
Cytokinetics begins Phase 2
trial of omecamtiv mecarbil in
Japanese subjects
SOUTH SAN FRANCISCO, Calif.—Early
April saw Cytokinetics Inc. announce
the start of a double-blind, randomized,
placebo-controlled, multicenter Phase 2
clinical trial to evaluate the safety, pharmacokinetics and efficacy of omecamtiv
mecarbil in Japanese subjects with heart
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DIAGNOSTICS
SANTA CLARA & CARLSBAD, Calif.—Agilent Technolo-
gies Inc. and Applied Spectral Imaging (ASI) opened
April with the announcement of an agreement to
jointly market ASI’s most advanced GenASIs imaging platforms, which offer advanced diagnostic
aids for pathologists and cytogeneticists, and
Agilent’s fluorescence in-situ hybridization (FISH)
products and solutions, including its Dako Omnis
instrument for automated FISH sample processing.
“Difficulty of fluorescence-based molecular
analysis has always been a major pain point for
our customers,” said Herman Verrelst, vice president and general manager of Agilent’s Genomics
Solutions Division and Clinical Applications Division. “We anticipate that Agilent’s broad portfolio of FISH reagents and instruments, and ASI’s
industry-leading computer-aided imaging solutions, will address such critical customer needs
and enable laboratories to have a standardized,
efficient and high-quality FISH workflow.”
White paper addresses breast
cancer diagnostic practices
CARPINTERIA, Calif.—Agilent Technologies Inc.
recently published a white paper on the role of
immunohistochemistry in diagnosing and treating
breast cancer, titled “Breast Cancer Diagnosis:
Past, Present and Future.” It is an overview of best
practices and covers how clinically meaningful
biomarkers and ancillary tests for breast cancer
have been established, as well as the potential
and shortcomings of using the biomarkers.
“By uniting morphological, immunohistochemical and molecular methods, pathologists can provide a comprehensive diagnosis that supports
individualized therapy for breast cancer patients,”
said Dr. Ping Tang, one of the co-authors from the
University of Rochester. “By covering useful antibodies and molecular tests in one comprehensive
source, we think this article will be a valuable
educational resource for breast pathologists.”
IN THIS SECTION
HIV/AIDS
Rheonix scores ‘positive’
with fast HIV test.................................... 32
Neglected tropical diseases
A new PATH for eliminating
tropical diseases (PATH from cover)........35
Oncology
Protagen identifies biomarkers
in prostate cancer.................................... 32
Translating signatures............................. 32
White paper addresses breast cancer
diagnostic practices................................ 32
Sample processing
Agilent teams with ASI
to co-market FISH solutions.................... 32
Translating signatures
Protagen
identifies
biomarkers in
prostate cancer
HalioDx, NanoString
Technologies to collaborate
on novel gene expression
assays in immuno-oncology
BY ILENE SCHNEIDER
MARSEILLE, France & SEATTLE—HalioDx
SAS, an immuno-oncology diagnostic company, and NanoString Technologies Inc., a
provider of life-science tools for translational
research and molecular diagnostic products,
have entered into an agreement to jointly
develop and commercialize advanced gene
expression assays for assessing the response
to immunotherapies.
The immune gene expression signatures
under this collaboration were discovered by
Dr. Jérôme Galon and his team at the Institut
National de la Santé et de la Recherche Médicale (Inserm). Galon has been a long-term
advisor of NanoString. HalioDx in-licensed
the signature patent portfolio from Inserm
and has selected the NanoString platform to
translate these signatures into a commercial
product for translational research and clinical use. HalioDx and NanoString have been
CREDIT: HALIODX
Agilent teams with ASI to
co-market FISH solutions
“At HalioDx, we want to develop diagnostic
solutions that can be easily used in routine
clinical practice settings, and we selected the
nCounter platform because of its robustness,
turnaround time and compatibility with
formalin-fixed, paraffin-embedded tissue
samples,” says Vincent Fert, co-founder and CEO
of HalioDx, pictured here on the right with other
HalioDx employees at a HalioDx exhibit booth.
engaged in collaboration discussions since
2015, and entered into a definitive agreement
this April.
NanoString and HalioDx will jointly develop assays based on the immune gene expression signatures on the nCounter platform.
GENE CONTINUED ON PAGE 33
Rheonix scores ‘positive’
with fast HIV test
Microfluidic system and assay can simultaneously
detect HIV antibodies and viral RNA
BY LORI LESKO
ITHACA, N.Y.—Global biotech and diagnostic
guru Rheonix Inc. has developed and tested
its microfluidic system and assay’s ability to—for the first time—simultaneously
detect host anti-HIV antibodies and viral
RNA, thus removing the anxiety of waiting
CREDIT: RHEONIX
BRIEFS
A promising new HIV assay is performed on
the Rheonix CARD (Chemistry and Reagent
Device), which is pictured here.
Findings represent
potential drug targets
supporting novel strategies
in precision medicine
BY JEFFREY BOULEY
DORTMUND, Germany—Protagen AG,
which describes itself as “a technology
leader in the development of novel
molecular diagnostic and companion diagnostic tests for autoimmune
diseases and oncological indications,”
announced recently the identification
of novel protein biomarkers in prostate cancer, which are potential drug
targets supporting novel strategies in
precision medicine.
Using the proprietary Protagen
SeroTag technology, the discovery
“[It] is really exciting
to learn more about
the links to the
immune system and
the appearance of
SPOP-specific
autoantibodies in
patient sera.”
Prof. Mark Rubin of
Cornell University
a month before the tested individuals find out
whether they actually test positive for HIV.
The researchers’ findings are outlined in
the Journal of AIDS & Clinical Research, in an
article entitled “A Rapid, Self-confirming
Assay for HIV: Simultaneous Detection of
Anti-HIV Antibodies and Viral RNA.”
The rapid Rheonix system improves HIV
testing by detecting early, acute HIV infection and addressing the well-known “seroconversion window” when antibodies are
not yet detectable, thus eliminating the
need for multiple patient visits to healthcare
providers.
The assay is performed on the Rheonix
CARD (Chemistry and Reagent Device).
Once a raw sample is placed on the Rheonix
CARD, the automated platform runs through
the process of sample extraction, purification, amplification and detection, Rheonix
reports. This eliminates the need for multiple pieces of existing equipment, helping
to make the testing process quicker, more
was made in close collaboration with
Prof. Helmut Klocker, of the Medical
University of Innsbruck in Austria and
the Oncotyrol Center for Personalized
Cancer Medicine in Innsbruck, and
Prof. Mark Rubin of Cornell University and Targos Molecular Pathology
GmbH in Kassel, Germany.
Measuring serum autoantibodies
in a liquid biopsy of prostate cancer
patients, the team was able to successfully confirm tissue specific biomarkers via immunohistochemistry.
“This is a novel route to new and
more specific biomarkers to allow for
better detection of prostate cancer
inflammation,” according to Klocker.
“In cooperation with Protagen, we
were not only able to identify new relevant prostate specific autoantigens—
RHEONIX CONTINUED ON PAGE 34
PROTAGEN CONTINUED ON PAGE 35
DIAGNOSTICS
GENE
fixed, paraffin-embedded tissue samples. Our co-developed
immune gene expression assays
will complement the breakthrough
Immunoscore IHC assay to foster
the development of more precise
immunotherapies.”
The products and services to be
developed under this agreement are
expected to enable researchers and
drug developers to use the assays to
assess responses to immunotherapies and select patients most likely
to benefit from the therapies. As
This could facilitate a wide variety
of basic research and translational
medicine applications, including
biomarker discovery and validation, according to Brad Gray, president and CEO of NanoString.
Vincent Fert, co-founder and
CEO of HalioDx, explained that by
precisely measuring the immune
reaction in and around the tumor,
HalioDx tests enable clinicians to
determine the degree of severity of
a patient’s disease and predict the
response to treatment, regardless
of the cancer stage or the molecular
class. Both companies will jointly
offer products and associated services to academic, pharmaceutical and
biotechnology customers worldwide.
NanoString and HalioDx are initiating the co-development efforts
for the research-use-only (RUO)
version of the immune gene expression signatures on the nCounter
platform. Both companies will
Fert explained, “We expect that the
co-developed immune gene expression assays will be increasingly
adopted in translational research
and clinical trials to develop clinically validated predictive biomarkers for cancer immunotherapies.
The assays have the potential to be
developed into CDx for immunotherapies in collaboration with biopharma companies in the future.”
While the companies said that
the commercial opportunity for
research assays is relatively mod-
est, it could become substantial
and closely correlated to the need
of predictive biomarkers for immunotherapies, depending on the
extent the gene signatures become
part of CDx products for use with
important new cancer treatments.
For a significant cancer indication,
hundreds of thousands of patients
might be tested each year.
“This collaboration with HalioDx
adds another powerful tool to the
nCounter immuno-oncology toolkit
to support our customers’ efforts in
Setting the stage for
the great minds of
diagnostics to
advance medicine
together
developing clinically validated predictive biomarkers for cancer immunotherapies. With the ability to process small tissue samples with minimal hands-on time, NanoString’s
nCounter technology provides a
powerful solution to researchers and
drug developers who are in search of
biomarkers for precision oncology,
and is ideally suited to answering
complex questions in translational
research in the field of immunooncology,” Gray concluded. n
PLENARY KEYNOTE
Implementing President
Obama’s Precision
Medicine Plan at the FDA,
and Changing the Current
Paradigm to Make Use of
Targeted Studies Involving
a Patient’s Specific Genetics, Health
History and Lifestyle
CREDIT: NANOSTRING
Elizabeth A. Mansfield, Ph.D., Director, Personalized
Medicine, Office of In Vitro Diagnostics &
Radiological Health, FDA CDRH
“This collaboration with HalioDx
adds another powerful tool to the
nCounter immuno-oncology toolkit
to support our customers’ efforts in
developing clinically validated
predictive biomarkers for cancer
immunotherapies,” says Brad Gray,
president and CEO of NanoString.
make “commercially reasonable”
efforts to make the initial RUO
product available for sale in the
second half of this year. Additional
RUO, investigational-use-only or
in-vitro diagnostic products incorporating the immune gene expression signatures may be developed
and made available at a later point
in time. Potential companion
diagnostics (CDx) may be developed and commercialized following execution of a CDx partnering
arrangement with a biopharmaceutical company in the future, according to the companies.
“We are excited to jointly develop our innovative predictive and
prognostic immune gene expression signatures on the nCounter
platform, one of the best multianalyte testing platforms for translating gene expression signatures to
routine diagnostic use,” Fert said.
“At HalioDx, we want to develop
diagnostic solutions that can be
easily used in routine clinical
practice settings, and we selected
the nCounter platform because of
its robustness, turnaround time
and compatibility with formalin-
Next Generation
SUMMIT
EIGHTH ANNUAL
MOVING ASSAYS
TO THE CLINIC
AUGUST 23-26, 2016 | GRAND HYATT, WASHINGTON, DC
CONFERENCE PROGRAMS (August 23-24)
Enabling Point-of-Care Diagnostics
Circulating Tumor Cells
Companion Diagnostics: Strategy & Partnerships
Coverage and Reimbursement of Advanced Diagnostics
DNA Forensics
Clinical NGS Assays
Hospital Laboratory Design and Renovation
NextGenerationDx.com
Cambridge Healthtech Institute,
250 First Avenue, Suite 300,
Needham, MA 02494
www.healthtech.com
CONFERENCE PROGRAMS (August 24-25)
Molecular Diagnostics for Infectious Disease
Clinical Application of Cell-Free DNA
Diagnostics to Guide Cancer Immunotherapy
Commercialization of Molecular Diagnostics
Leveraging Pharmacies for Rapid Diagnostics
NGS Diagnostics: Data Considerations, Annotation and Interpretation
SYMPOSIA (August 26)
Advances in Microbiome Diagnostics
Predictive Cancer Biomarkers
Non-Invasive Prenatal Testing
Health and Wellness Genomic Screening
The Business of Telemedicine
Digital PCR
DIAGNOSTICS
Avant and Amarantus Diagnostics to combine
operations with Theranostics Health
Avant Diagnostics Inc., a biotechnology
company focused on the development of
oncology-based diagnostics, and Amarantus
Diagnostics Inc., a wholly owned subsidiary
of Amarantus BioScience Holdings Inc.,
recently announced that the companies
have jointly entered into a letter of intent
for Avant to acquire assets and certain liabilities of Theranostics Health Inc. (THI),
adding key CLIA laboratory and intellectual
property capabilities to Avant’s previously
announced letter of intent to merge with
Amarantus Diagnostics.
THI currently generates over $1.5 million
in services revenue from some of the world’s
leading biopharmaceutical companies,
including seven of the top 10 pharmaceutical companies by revenue.
Under the terms of the letter of intent,
Avant shall issue to THI 25 million shares
of its common stock upon the closing. Amarantus BioScience has provided a convertible note of $400,000 to THI to facilitate the
transaction that will be assumed by Avant
upon closing of the transactions. As previously disclosed, Avant plans to issue 80 million shares of its common stock to Amarantus
Biosciences upon completion of its merger
RHEONIX
vices revenue base and sales channel in the
area of cell signaling biology,” said Gregg
Linn, president and CEO of Avant Diagnostics. “In addition to this, THI’s CLIA
laboratory provides the combined company
with the infrastructure to launch OvaDx,
MSPrecise and LymPro Test in a regulatory-compliant environment that has been
vetted by some of the world’s top pharmaceutical companies. THI’s laboratory meets
the highest-quality standards under CLIA/
CAP, which should give both our pharmaceutical and commercial customers great
confidence in the information generated in
THI’s laboratory.”
THI’s core business is centered on providing pharmaceutical and biotechnical companies access to its technology for quantitatively measuring the activation status of
key proteins and signal transduction pathways that are dysregulated in multiple disease processes via its Reverse-phase Protein
Array (RPPA) platform. THI is experienced
in running CAP-accredited assays in its CLIA
laboratory for predicting response to therapies in difficult to treat cancers. THI believes
that, while genomic approaches may identify
potential activating mutations in diseased tissues, measuring the actual activation status
simple “dipstick-like” tests that lack sensitivity and specificity.
“Our technology meets the needs of settings with limited resources,” Gregory J.
Gavin, Rheonix CEO and chairman, stated
in a press release. “The assays are rapid,
sensitive, specific, easy to perform and inexpensive. This combined HIV screening and
confirmatory test will have a significant commercial and social impact that we’re excited
to see materialize.”
Principal investigator Richard Montagna,
Rheonix’s senior vice president for scientific and clinical affairs, stated, “In collaboration with scientists at NYU, we were able
to demonstrate how our system can detect
both the HIV antibodies and the actual viral
RNA, even in the earliest stages of the disease, to immediately confirm whether or
not a patient is infected. The fully automated testing system will allow resource-
limited regions of the world to have their
first-ever opportunity to perform simultaneous serological testing and molecular
confirmation for HIV.”
“The well-known ‘seronegative window’
period is caused by the fact that the body’s
immune system doesn’t produce antibodies against HIV until weeks or months after
infection, but the viral RNA is essentially
present immediately after infection,” Montagna told DDNews. “The ability to detect that
viral RNA causes the ‘window period’ to be
dramatically shortened. Theoretically, that
period can be shortened to a few days.”
“Our goal was to develop a test for ‘pointof-care’ use in the developing world, and since
the technical resources are limited in such
settings, most current testing relies on less
accurate testing methods,” Montagna continued. “Therefore, once we have approval to sell
our dual assay in these settings, healthcare
workers will have access to more accurate test
results and be able to establish the infection
status of individuals seeking care.”
In addition, “since the majority of rapid
tests rely on detecting the presence of antibodies, any individuals who may have been
recently infected and have not yet produced
detectable antibodies, would be scored as
‘negative,’” he said.
This is complicated by the fact that many
would-be HIV-positive patients fail to return to
the clinic for that crucial second visit and accurate HIV test results, healthcare officials report.
Rheonix’ ability to simultaneously detect
the presence of both antibodies and viral
RNA will allow individuals who have been
recently infected by HIV to be scored as “positive” in a day or two. Therefore, individuals
who may have been unaware of their infection status may be more accurately scored as
“positive” for HIV during that first visit, and
thus be more amenable to accepting thera-
CREDIT: RHEONIX
efficient, less expensive and less likely to
result in human error.
The global HIV/AIDS epidemic continues to be fueled by the large number
of individuals who are unaware they are
infected, or who have limited access to
advanced diagnostics. Governments and
nongovernmental organizations around the
world support various programs to reduce
the impact of the disease by encouraging
more frequent testing. Current technologies require confirmation of a positive test
result by a second, more sensitive and more
specific test, according to Rheonix. However, low-resource settings often lack the
sophisticated equipment, trained personnel and facilities required to effectively test
clinical specimens, and they often rely on
with Amarantus Diagnostics. The transactions are expected to close in the first half of
2016, and are subject to customary closing
conditions.
“THI is a leader in the area of signal transduction biology, where they have been able
to attract an A-list of pharmaceutical customers collaborating with the company to
evaluate the therapeutic benefit and potential of their drug candidates using THI’s
proprietary assays,” said Gerald E. Commissiong, president and CEO of Amarantus. “In
addition, THI has a CLIA lab where Amarantus Diagnostics has established operations
over the course of the first quarter that will
allow for CLIA validation and commercial
launch of the combined company’s suite of
high-value, proprietary diagnostics in the
areas of oncology and neurology. THI’s sales
channel into the pharmaceutical industry
will provide important leverage for the combined company to market the LymPro Test
for Alzheimer’s disease. We could not have
picked a better partner to bring Avant and
Amarantus Diagnostics’ leading-edge intellectual property in diagnostics and biomarkers to the market.”
“Key to the business case for the merged
company is THI’s impressive pharma ser-
Other Rheonix technology in addition to the Rheonix CARD includes the EncompassMDx
Workstation pictured here. The company’s focus is on “making molecular diagnostics available
to more people, in more places, more often.”
of the protein drug targets and the signal
transduction pathways that they regulate
provides physicians with much-needed evidence that a particular therapeutic strategy
can provide benefits to the patient.
THI has launched tests, TheraLink Assays,
for guiding therapeutic decisions in breast
and colorectal cancer. The post-merger Avant
Diagnostics will further build on its recognized scientific expertise in the area of cell
cycle biology to increase its pharma services
revenues and provide therapy-guiding diagnostics in difficult-to-treat conditions.
“After an extensive evaluation of the diagnostics market, we believe that we have
found the best potential partners in Avant
and Amarantus,” commented Dr. Glenn
Hoke, CEO of THI. “It is clear that we will
be expanding our CLIA offerings with muchneeded tests, such as OvaDx in cancer and
MSPrecise in neurology, while also providing significant additional pharma services
business development opportunities with
the LymPro Test. With platforms in microarray proteomics, ELISA, flow cytometry
and ‘next-gen’ sequencing, the combined
company’s capabilities will allow it to add
cross-platform diagnostics as we grow into
the future.” n
CREDIT: RHEONIX
SCOTTSDALE, Ariz. & SAN FRANCISCO—
“In collaboration with scientists at NYU, we
were able to demonstrate how our system
can detect both the HIV antibodies and the
actual viral RNA, even in the earliest stages of
the disease, to immediately confirm whether
or not a patient is infected,” says Richard
Montagna, Rheonix’s senior vice president for
scientific and clinical affairs.
peutic intervention.
The Rheonix “smart” CARD was invented
in 2005 by Peng Zhou, chief scientific officer and senior vice president of research and
development at Rheonix, and Lincoln Young,
an engineer at Rheonix, Montagna said, adding, efforts by a “myriad of people have further
advanced the technology to its current state.”
Rheonix plans to “initiate clinical studies
in the United States this year for its instrument and CARD test for the presence of three
sexually transmitted infections,” according to
Montagna. “The development efforts for the
HIV ‘dual assay’ are currently being funded
by the National Institute of Dental and Craniofacial Research of the National Institutes
of Health, and those efforts will continue
for at least six more months as we strive to
further reduce the total time required to perform the assays.” n
DIAGNOSTICS
PROTAGEN
e.g. SPOP, SPAST, STX 18—but also
show the orthogonal validation of this
serum marker on tissue microarrays
with our partners at Targos.”
“We’ve been working on the role of
SPOP and its mutations in prostate
cancer for quite some time. It is really
exciting to learn more about the links
to the immune system and the appearance of SPOP-specific autoantibodies
in patient sera,” Rubin added.
“It is always a good cross-validation
when two independent methods yield
the same result. Validated biomarkers
in immune oncology and other immune
diseases are a valuable asset. We are very
excited to work with Protagen together
in this emerging field,” commented Dr.
Thomas Henkel, CEO of Targos.
Added Stefan Müllner, CEO of Protagen: “There’s an unmet diagnostic need
in prostate cancer diagnostics, and the
commercial value of novel, more reliable options that don’t involve biopsies
and improve follow-up of patients are
very attractive.” He also expressed pleasure that a study published recently in
PLOS ONE, “Serum autoantibodies in
chronic prostate inflammation in prostate cancer patients,” in collaboration
with his company’s partners “underscores that SeroTag technology can
significantly speed up diagnostic developments. Furthermore, SPOP plays a
key role in the function of E3 ubiquitin
ligase, which is a novel and interesting
pathway for therapeutic intervention in
cancer. Thus, the data presented in this
paper also introduce a novel concept for
drug target identification for stratified
therapy and personalized medicine.”
Protagen specializes in the development of novel diagnostic and companion diagnostic tests to provide better
and earlier diagnosis of autoimmune
diseases and oncological indications.
The diagnostics are very much
intended to help drive drug discovery
efforts, with Protagens’s chief business
offer, Dr. Georg Lautscham, telling
DDNews, “SeroTag is the immune system’s guide to novel drug targets. The
generation of autoantibodies implies
that these proteins are important in
the disease process and therefore
pinpoint to relevant cellular pathways and potential drug targets. The
interlink between these targets and
the presence of autoantibodies in
human serum enables the selection
of appropriate patient populations
for more targeted and more efficient
therapies, i.e. a true precision medicine approach.”
Currently, Lautscham says, Protagen is looking for pharma cooperation
partners, especially in autoimmune diseases, but the research shows that applications in other areas, like oncology,
generate relevant and attractive results.
“This is a new business opportunity for Protagen we are following,” he
adds. “Our unique data repository from
around 14.000 patients from more than
20 indications offers excellent opportunities for our cooperation partners and
licensing options for Protagen.” n
PATH
eliminate these NTDs and will contribute
to surveillance programs and public health
management with qualified products.”
The first of the two new diagnostic tools
is an onchocerciasis and LF dual-detection,
or “biplex” test. It is designed to close holes
in surveillance data for both diseases’ control
programs in parts of Africa where they are coendemic. This could help reduce the cost to
control programs, simplify use and logistics
and improve coordination of decision-making among control programs. The biplex test
can support such programs as they move to
the disease elimination phase by monitoring
post-control areas and detecting cases in lowprevalence areas. The SD BIOLINE Onchocerciasis and Lymphatic Filariasis IgG4 rapid
test is based on the detection of antibodies
to parasite antigens Ov16 for onchocerciasis
and Wb123 for LF. Those antigens were identified and characterized by scientists at the
National Institute of Allergy and Infectious
Diseases at the National Institutes of Health.
The second test is an LF monoplex test that
can also be used in endemic areas where mass
drug administration (MDA) has been ongoing for several years. Using antibody-detection
tests in such areas can provide important
information about recent transmission rates,
and data from surveillance studies can be
used to support decisions to continue, halt or
reinstate MDA efforts. The SD BIOLINE Lymphatic Filariasis IgG4 rapid test is based on the
detection of antibodies to Wb123 for LF alone.
Funding for the development of these tests
came from the Bill & Melinda Gates Foundation. PATH is actively seeking partners to
undertake demonstration and operations
research studies using the new tests, and
will offer technical assistance and training
materials to implementation partners.
Jeffrey Wellhausen, commercialization
officer at PATH, says that several NTDs,
including onchocerciasis and LF, can be
treated with MDA, and over time, disease
This is the scene many people associate with tropical locales, but many of them are also home
to a host of neglected diseases, including lymphatic filariasis and onchocerciasis—both of
which now have rapid diagnostic tools thanks to PATH and Standard Diagnostics/Alere.
levels will drop. While obviously that is the
goal, it also makes disease detection more difficult, “because the very low levels of parasites
remaining are much more difficult to detect,
particularly when people don’t show signs of
active disease.” Detecting those low levels are
important, he notes, because stopping MDA
too soon could allow the disease to return.
“Because the new tests that PATH and SD/
Alere have launched detect prior disease, they
can be used in regions that have undergone
years of MDA, where almost no one will have
active infections … In the case of onchocerciasis, if children under the age of 10 show
no evidence of exposure when tested, this
indicates that transmission has been halted
for 10 years, and stopping MDA can be considered (which corresponds to the WHO’s
recommendations). In regions where MDA
has been halted, any new infection would also
be found through periodic testing,” he adds.
“Funding to fill the market need for these
diagnostics is not assured, but one of the
important aspects of these rapid tests is that
they are standalone surveillance tools requir-
ing no infrastructure, and they are low-cost
(the Ov16 test costs $1.20),” says Wellhausen.
“This makes the product suitable for largescale uptake in the resource-poor environments where they are needed.”
Onchocerciasis, also known as river blindness, is caused by a parasitic worm transmitted to humans through the bite of the blackfly. It is thought that worldwide, 169 million
people are at risk for river blindness and 37
million are infected. Of those at risk, 99 percent live in Africa.
LF, the major cause of elephantiasis, is
spread via mosquitoes. The disease damages
the lymphatic system, resulting in serious disability, disfigurement and low quality of life
across Africa and parts of Asia. Approximately
120 million people are infected with LF worldwide, with some 1.23 billion at risk. Wuchereria bancrofti is one of three species of parasitic
worms responsible for LF and accounts for 90
percent of the infections globally, including all
cases on the African continent. These diseases
are commonly seen in the same communities. n
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CONTRACT SERVICES
Envigo gains AAALAC ccreditation
HUNTINGDON, U.K.—Envigo has announced that
its Horst, Netherlands, site has received full
accreditation from the Association for Assessment and Accreditation of Laboratory Animal
Care (AAALAC) International Council. In addition
to this accreditation, the Horst facility is also
ISO certified. The site is one of the company’s
largest European research models and services
facilities, with five barrier units and a transport
hub for distributing Envigo research models and
Teklad laboratory animal diets to over 700 customers across Europe and Asia. In conjunction
with seeking the AAALAC accreditation, Envigo
has renovated two major barrier units, improving
building maintenance and biosafety, and ensuring compliance with new EU/2010/63 guidelines
regarding cage densities. Further renovations are
planned for two additional Horst barriers.
AMPAC boosts capacity
RANCHO CORDOVA, Calif.—Thanks to its ongoing
expansion of facilities in Rancho Cordova and in
La Porte, Texas, AMPAC Fine Chemicals LLC (AFC)
has increased its total capacities by 50 percent
since 2013, the company announced recently.
Its most recent High Potency facility “SemiWorks#4” is fully operational, and construction
has begun on a large-scale site that will come
online late this year.
“AFC is witnessing robust customer demand
for our core technologies combined with our
development and manufacturing expertise to
support drug candidate maturation from clinical
trials into commercial production,” Dr. Aslam
Malik, CEO of AFC, said in a press release. “To
meet this demand, we are investing over $40
million in 2016 for capacity expansion and infrastructure enhancements. AFC’s plant expansion is
supported by the financial backing of H.I.G. Capital, a major international investment firm with
$19 billion under management.”
IN THIS SECTION
Accreditation
Envigo gains AAALAC accreditation....... 36
Antibodies/Proteins
LakePharma showcases antibody
discovery and protein engineering
expertise at PEGS Boston 2016............... 38
Expansion/Strategy
AMPAC boosts capacity.......................... 36
Robust rebuilding.................................... 36
Immuno-oncology/
M&A activity
Crown makes oncology,
cardiovascular and metabolic strides..... 36
Structural biology
and analysis
A ‘triple win’............................................ 36
A ‘triple win’
NovAliX and FEI partner up to
provide Cryo-EM to biopharma
BY LORI LESKO
ILLKIRCH, France— Taking a
giant step toward developing
more powerful drugs in less time
and at cheaper costs, French
contract research organization
(CRO) NovAliX has partnered
up with Hillsboro, Ore.-based
FEI to bring commercial cryoelectron microscopy (EM)-based
structural analysis services to
its global pharmaceutical and
biotech clients. Having access
to cryo-EM gives customers
an edge on the market with its
three-dimensional view of structures under conditions much
closer to the native intracellular
environment, the companies say.
Cryo-EM has quickly become
one of the most important techniques used by structural biolo-
gists today to obtain 3D information about protein structures, the
partners add. When combined
with traditional methods for
structure determination, such as
X-ray crystallography and nuclear magnetic resonance (NMR)
spectroscopy, the resulting
models can reveal the structure
of complex, dynamic molecular
assemblies down to the scale of
individual atoms.
The collaboration combines
NovAliX’s integrated cryo-EM
workflow based on a transmission electron microscope (TEM)
and FEI’s combined application,
training and support with onsite
personnel.
“There is a growing demand
for structural studies from the
pharmaceutical industry, driven
Cryo-EM is an important technique for structural biologists to obtain
3D information about protein structures, FEI and NovAliX note.
Pictured here is a rendering of the SARS virus.
by the need for a deeper scientific understanding and because of
stronger regulatory constraints,”
Denis Zeyer, CEO of NovAliX,
stated in a news release.
In the field of biologics, EM
analysis has proven to be capable
of delivering critical information
for antibody selection, epitope
TRIPLE CONTINUED ON PAGE 38
Robust rebuilding Crown makes oncology,
Vetter groundbreaking is a major
cardiovascular and
element of investment strategy
metabolic strides
BY ILENE SCHNEIDER
RAVENSBURG, Germany— Vetter recently held a groundbreaking for the construction of a
new building at its Ravensburg
Schuetzenstrasse site. The company expects to complete the
building in the first quarter of
2018 and begin operations there
in early 2019.
Projecting a cost of about €70
million (about $79 million),
Vetter described the building
as “part of the total investment
strategy announced in September 2015” and “an important
element in the overall Schuetzenstrasse facility rebuilding
concept for modernization and
expansion.” Vetter, a contract
development and manufacturing organization (CDMO) for
the development, commercial
manufacturing and final packaging of aseptically prefilled drugdelivery systems, plans to invest
about €300 million to expand
Crown strengthens immuno-oncology
capabilities with HuGEMM and acquires
PreClinOmics to expand cardio and
metabolic disease portfolio
BY JEFFREY BOULEY
CREDIT: VETTER
BRIEFS
SANTA CLARA, Calif.—April and March were good months for
and upgrade its manufacturing
facilities over an estimated fiveyear period.
“We are continuously monitoring and reacting to a changing
Crown Bioscience, a wholly owned subsidiary of Crown Bioscience International, in terms of expanding the capabilities of
the global drug discovery and development services company,
which provides translational platforms to advance oncology
and metabolic disease research.
The most recent news came in the form of an announcement
that Crown Bioscience had developed and validated a unique
set of models for immuno-oncology called HuGEMM.
“Up until now, the lack of models available to test the in-vivo
efficacy of new antibody-based immunotherapies and combination therapies has hindered the research process,” according to Dr. Jean-Pierre Wery, president of Crown Bioscience.
“With HuGEMM, there is now a robust model system in place
to enable scientists to assess the efficacy of human biologic
therapeutics directly without resorting to mouse surrogates.”
Syngeneic mouse tumor models, commonly used for test-
VETTER CONTINUED ON PAGE 39
CROWN CONTINUED ON PAGE 38
In addition to the Ravensburg
Schuetzenstrasse expansion, two
other Vetter facility expansions are
already ongoing, at its Ravensburg
Vetter West and Ravensburg
Vetter South locations. Pictured
here is the groundbreaking for
the new Ravensburg
Schuetzenstrasse building.
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OF NEWS
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new marketed therapeutics is an
on-going challenge. In DDNews, you
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CONTRACT SERVICES
LakePharma showcases antibody
discovery and protein engineering
expertise at PEGS Boston 2016
Company celebrates the combination of LakePharma with
Blue Sky BioServices to create largest dedicated biologics CRO
BELMONT, Calif.—LakePharma, a leading pro-
tein engineering contract research organization (CRO) dedicated to providing integrated
biologics discovery and development services,
presented key data at the PEGS 2016 Protein
Engineering Summit in the form of several
case studies highlighting the challenges that
arise from the multiple domain nature of
fusion protein therapeutics. Specifically, Dr.
Hua Tu, LakePharma’s chairman and CEO,
shared data for the design, engineering, bioanalytical characterization and manufacturability assessment of Fc fusions and bispecific
antibodies.
Company scientists also presented a poster
detailing a tandem mass spectrometry approach
to proteomic sequencing that enables the
accurate determination of an antibody’s primary sequence when the source hybridoma
is unavailable. In addition to revealing the
full sequence of an important antibody, their
approach enabled the engineering of the antibody to improve its production by CHO cells, as
well as its performance as a purification reagent.
Details on Presentation
Overcoming Multiple Domain Challenges
of Fc Fusions and Fab Fusion Bispecific
Antibodies
Speaker: Hua Tu, Chairman and CEO, Lake
Pharma, Inc.
Track: Fusion Protein Therapeutics: Engi-
neering Enzymes
Authors: Natalie Castellana, Digital
Proteomics; Kexin Huang and Hua Tu,
LakePharma
“As specialists in antibody discovery and
protein engineering, our bicoastal team is
well positioned to offer pharmaceutical and
biotechnology companies the most comprehensive continuum of services to enhance
the quality and speed of their biologics discovery and development,” said Tu.
TRIPLE
mapping and formulation, Zeyer said. With
small-molecule research programs, cryo-EM
can be uniquely valuable to obtain structural
information on multiprotein complexes or
membrane proteins, which is key to understanding the structure-function relationship.
“During the latest NovAliX conference, we
have witnessed the interest and the relevance
of biophysical tools in drug discovery,” Zeyer
said, “so this new offering will nicely complement our structural biology and biophysical
platform that includes X-ray, NMR, surface
plasmon resonance and native mass spectrometry. Now with cryo-EM available, NovAliX
scientists are able to deliver critical insights
into the biology of protein complexes. Indeed,
we will be able to fit X-ray structural results
of individual proteins with a global structural
view of the complex obtained by cryo-EM,
which is otherwise not easily accessible.”
Zeyer tells DDNews, “Cryo-TEM now can
be used for the structure determination of
Celebration of Merger with
Blue Sky BioServices
The company invited all PEGS Boston attendees to join the LakePharma team at a cocktail
party celebrating LakePharma’s acquisition of
Blue Sky BioServices.
“The joining of LakePharma and Blue Sky
BioServices at the end of March has created the U.S. biotech and pharmaceutical
industry’s largest CRO dedicated to biologics,” said Tu. “Together, our comprehensive capabilities in antibody development,
protein expression and characterization,
molecular biology and protein analytics
provide a full continuum of services for discovery and early-stage biotherapeutic development. Moreover, with four facilities in
the San Francisco Bay Area and Cambridge/
Boston areas, we’re based right where our
clients are—in the nation’s greatest biotech
hubs.”
About LakePharma
LakePharma is a CRO dedicated to serving
the discovery research and protein engineering needs of companies engaged in the development of biotherapeutics. The company has
assembled what it says are the United States’
most comprehensive suite of technologies
and expertise to offer a large continuum of
services for antibody and protein discovery
and engineering, cell line creation and protein analytics.
Clients can access the company’s services
individually or as a fully integrated “soup to
nuts” solution for all of their molecular biology, protein chemistry, cell line, assay and
production scale-up needs.
Moreover, LakePharma provides what it
says are “superior client services and sophisticated software to provide real-time access to
project data via a secure cloud-based portal,
Datasystems.” n
membrane bound proteins like ion channels
up to near atomic resolution, revealing the
side-chain arrangements required to understand their gating mechanisms. Hence, cryoTEM is seen by NovAliX as a powerful alternative for doing structure-based drug design
on this protein family.
X-ray crystallography “is the gold standard
for structural studies, but is limited for the
analysis of complex molecular target like
membrane bound proteins or large molecular
assemblies as the crystallization of such proteins is highly challenging,” Zeyer said. “Integration of the cryo-TEM in our technology
portfolio and workflow will enable us to work
on such targets and allow us to provide invaluable structural information for the successful
development of novel clinical candidates.”
Peter Fruhstorfer, vice president and general manager of the Life Sciences business
at FEI, also speaks positively of the benefits
of cryo-EM models. He stated that cryo-EM
3D models “allow us to see and understand
the workings of protein-based molecular
machines that we could not analyze before
CROWN
record and scientific reputation in the
CVMD research and pharmaceutical
ing surrogate anti-mouse PD-1 antibodies, industry,” noted Dr. Jim Wang, senior vice
cannot serve as models for human-specific president of CVMD research at Crown
therapeutics, according to CrownBio, and Bioscience.
PreClinOmics was incorporated in
its HuGEMM platform, which was developed by directly replacing the murine PD-1 Indianapolis in 2001. It is an AAALACaccredited solutions provider
protein with its human counto the pharmaceutical industry
terpart, can be used to evaluate
in areas that include discovery
human therapeutics for checkservices, analytical services,
point inhibitors including but
ADME/PK services, safety/
not limited to antihuman PD1,
non-GLP toxicology services
antihuman PDL-1 and antihuand genetic models. The comman CTLA-4 antibodies.
pany works with clients in the
With the inclusion of the
pharma industry from large
HuGEMM models, CrownBio
corporations all the way down
believes it has solidified its role “With HuGEMM,
to virtual start-ups.
as a leader in the preclinical there is now a
“The drug development
immuno-oncology space, and robust model
notes that HuGEMM joins a system in place to industry will now have a single
source that offers the best modportfolio of well-established enable scientists
to assess the
els available in both cardiovastranslational model platforms, efficacy of human
cular and metabolic diseases,”
including the collection of biologic
said Joseph Pesek, CEO and
HuPrime cancer models avail- therapeutics
co-founder of PreClinOmics.
able through the company’s directly without
resorting to
With this acquisition,
HuBase annotated database.
CrownBio says it is demonThe HuGEMM models were mouse
says
strating its commitment to
developed along with Crown- surrogates,”
Dr. Jean-Pierre
Bio’s partner, Nanjing Galaxy Wery, president of expanding its global reach as
an end-to-end solution for
Biopharmaceutical Co. Ltd.
Crown Bioscience.
CVDM research, in addition
And, a bit more than a
month earlier, CrownBio announced that to its existing oncology franchise, notits capabilities in two other therapeutic ing that PreClinOmics has cutting-edge
areas grew with the acquisition of PreCli- technologies that support a broad range
nOmics Inc., an in-vivo preclinical compa- of study designs, including metabolic synny specializing in early research in cardio- drome, obesity, diabetes, cardiovascular,
vascular and metabolic diseases (CVMD) renal and neurology.
CrownBio notes in particular that,
as well as renal disease. With this acquisition, CrownBio adds to its portfolio what unlike other commercially available
it calls “some of the most relevant CVMD models, the models in the PreClinOmics
product line develop adult onset type 2
models to replicate human disease.”
CrownBio’s president adds: “The acqui- diabetes and all the diabetic complicasition of PreClinOmics will allow Crown- tions without relying on mutations in
Bio to create a center of excellence in the leptin signaling. This is important,
global translational drug development spe- according to CrownBio, because mutacifically for cardiovascular and metabolic tions in the leptin gene/receptor have
disease,” and Wery further goes on to say, never been identified as relevant to the
“We are confident that the acquisition will onset of the human disease.
PreClinOmics’ name will not dissolve
ultimately result in greater success in clinical trials and lower the cost of drug devel- after the acquisition. Instead, the comopment for diseases that produce some of pany will be referred to as “PreClinOmics,
the highest economic costs in the world.” a Crown Bioscience company.” n
“PreClinOmics has an excellent track EDITCONNECT: E051626
CREDIT: CROWN BIOSCIENCE
because they were too large and complex or
were resistant to the preparations required
for other techniques.”
“The power and value of cryo-EM based
structural analysis is evident from the quality of recent publications by academic and
industry researchers,” according to Fruhstorfer. “This collaboration with NovAliX is an
important step in the broader commercialization and industrialization of the technology.”
The recent advances in cryo-EM “put this
method at the forefront of life sciences, and
now enables scientists to look into large protein complexes at near atomic resolution,”
Fruhstorfer tells DDNews. “It opens a new
perspective in the field of drug discovery.”
For the first time, “therapeutic relevant
protein complexes can be studied in their
native state,” he adds. “The partnership
between NovAliX and FEI helps to make
cryo-EM structural studies accessible for
the pharmaceutical industry in order to gain
higher success rates and effectiveness.”
In addition, “single-particle cryo-TEM
can be used to map epitopes at intermedi-
ate resolution to understand precisely how
therapeutic antibodies bind their targets,
allowing researchers to only focus X-ray
studies on the most promising antibodies
for high-resolution studies as that approach
is time consuming,” Fruhstorfer said.
This is the first partnership between FEI
and any CRO company, according to Fruhstorfer, who notes that this model of partnership
“makes cryo-EM accessible and more affordable to larger number of NovAliX clients.”
“At present, the role of CROs is critical
because of a strong increase of outsourcing
in the global pharmaceutical industry in an
effort to access novel technology, increase the
critical capacities and shorten the time of the
drug development process,” Fruhstorfer says.
“FEI is in the unique position to develop its
technology and expertise while enabling our
CRO partner, NovAliX, in serving better its
pharmaceutical customers.”
“This is indeed a triple-win combination
for FEI, NovAliX and our clients,” he concludes. n
VETTER
marketplace and are pleased that we are in
the position to be able to make these strategic investments to further develop our sites
and meet these challenges,” Vetter Managing Director Peter Soelkner tells DDNews.
“Individually and collectively, they will help
us keep pace with the market and allow us
to continue to build a successful future for
Vetter and our customers.”
Other Vetter facility expansions are already
ongoing at several of the company’s German
locations, including its Ravensburg Vetter
West center for visual inspection and logistics. Structural work for the facility enlargement, which will offer more than double of
its current capacity, is completed, and the
site is expected to become fully operational
in 2017. In addition, the Ravensburg Vetter
South production site has also been designated for significant enlargements as is the
Ravensburg Schuetzenstrasse facility where
initial construction activities began in 2013.
All three site expansions will result in additional capacities for drug product manufacturing and logistic services.
Thomas Otto, also a Vetter managing
director, says that the CDMO is “continuously developing its manufacturing sites and
techniques to prepare them for future needs
and requirements.” The upgrades are “being
driven by a changing healthcare market
that is affected by issues such as ever-more
complex molecules, smaller batch sizes and
increasing regulatory requirements,” he adds.
When finished, the seven-story Ravensburg Schuetzenstrasse building will cover a
total of 8,000 square meters (86,000 square
feet) and include a cleanroom with supportive media systems. In addition, it will contain
the site’s central material preparation, office
space for the production staff and a staff canteen with roof garden.
The applied technology of the cleanroom
will be “dedicated to the filling of bulk
syringes and designed to be compatible for
the filling of sensitive drugs such as biologics
and opthalmics,” Otto explains, adding that
syringes prepared in the bulk process offer
a number of customization options that are
tailored to substance and primary packaging
material components. They offer customizable low silicone levels and, thus, process
flexibility.
Another key technological aspect of the
cleanroom will be the implementation of
an improved restricted access barrier system (RABS) concept to combine the advantages of isolator and RABS technology. For
decades, Vetter has relied on RABS as one
of the two distinct technologies available
today for its aseptic filling processes, the
other being isolators. RABS achieves the
sterility assurance level required by regulatory authorities, and allows for rapid product change-over coupled with high safety. To
better meet future industry trends in quality,
safety and flexibility, a corporate project team
has evolved this “improved RABS concept”
by combining the advantages of isolator and
RABS technology.
“The core of this innovative approach is a
uniquely fast, by today’s standards—a threehour cycle and fully automated decontamination of the cleanroom using hydrogen peroxide (H2O2),” Otto says.
Vetter works with the top 10 biopharmaceutical companies, as well as small
and midsize companies, on state-of-the-art
manufacturing from early clinical develop-
ment through commercial filling and final
packaging of parenteral drugs. The company
covers a broad range of complex compounds
including monoclonal antibodies, peptides
and interferons.
“This addition to our Schuetzenstrasse
site is an exciting chapter in our company’s
history and will again support Vetter’s target to offer its customers high manufacturing quality for their high-value drugs,” noted
Otto in the news release about the expansion.
“Attaining this high level of quality is of particular significance to Vetter.” n
CREDIT: VETTER
CONTRACT SERVICES
Vetter is expanding it Ravensburg Schuetzenstrasse site with a new building at a projected
cost of around $79 million.
Paying too much for too little?
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BUSINESS &
GOVERNMENT POLICY
EMERYVILLE, Calif.—Industrial bioscience company
Amyris Inc. has inked a stock purchase agreement
with the Bill & Melinda Gates Foundation for a
$5-million equity investment. Per the agreement,
the Gates Foundation will purchase roughly $5 million of Amyris common stock at $1.14 per share,
the average daily closing share price for the 20
days prior to the signing. The closing was expected
to occur on or about April 29, subject to customary closing conditions. This investment will fund
a program aimed at further reducing the cost of
one of the world’s leading malaria treatments,
with a focus on the continued production of highquality, secure supplies of artemisinic acid and
amorphadiene to be converted to artemisinin for
use in artemisinin combination therapies, which
are recommended by the World Health Organization as the primary first-line treatment for malaria.
iCardiac renames
respiratory service line
ROCHESTER, N.Y.—iCardiac Technologies Inc. has
announced the launch of “PFT Global,” the new
name of its respiratory testing service line, the end
result of its efforts to integrate the clinical trials
division of nSpire Health, which iCardiac acquired
in July 2015, into the company. iCardiac’s respiratory service line supports clinical trials in Phase
2 and 3, covering studies of all sizes, from those
with few sites and participants to multi-center
global studies with participants in the thousands.
“This renaming was the culmination of our comprehensive efforts to integrate our acquired respiratory services into iCardiac,” said John Sage, senior
vice president of Respiratory and ePRO at iCardiac.
“As a result of the integration, our sponsors will benefit from various enhanced capabilities, including our
broader capacity and resources in relation to project
management, site support and global logistics.”
IN THIS SECTION
Business/Strategy
Change on the way for GSK.................... 40
iCardiac renames
respiratory service line............................ 40
Health policy/Innovation
Innovation impact.................................... 40
Infectious disease
Gates Foundation to invest
$5M in malaria effort.............................. 40
M&A activity
Biggest pharma combo becomes
biggest bust (PFIZERGAN from cover)..... 43
Pharmacovigilance
Bioclinica and ArisGlobal seek to
transform pharmacovigilance.................. 40
Tools and technology
On the cutting edge................................. 42
Innovation impact
Bioclinica and
ArisGlobal seek to
transform
pharmacovigilance
U.S. ranks first in ITIF
analysis of policy impact on
life-sciences innovation
BY KELSEY KAUSTINEN
WASHINGTON, D.C.—The Information Tech-
nology and Innovation Foundation, (ITIF), a
global technology policy think tank, marked
this year’s World Health Day with an analysis of how different countries’ domestic
policies affect life-sciences innovation on
a global scale. The report, “How National
Policies Impact Global Biopharma Innovation: A Worldwide Ranking,” found that of
56 countries comprising nearly 90 percent
of the world’s economy, the United States
ranks first in terms of the impact of its scientific research, drug pricing and intellectual
property policies on global biopharmaceutical innovation.
The study focused on three policy areas
that support life-sciences innovation domestically and also have positive spillover effects
globally: governments’ R&D expenditures on
health, the extent of price controls on biopharmaceutical drugs and intellectual property protections for life-science innovations.
CREDIT: ITIF
Gates Foundation to
invest $5M in malaria effort
“As long as countries continue to put the right
conditions in place—robust investment in lifesciences R&D, strong intellectual property
protections and drug pricing policies that
balance access to medicines with financial
returns for innovators—we should expect to
continue to see robust rates of biomedical
innovation,” says Stephen Ezell, ITIF vice
president for global innovation policy.
watchers are hoping for a whiff of change
in the air between now and March 31, 2017,
when Witty will retire from GSK.
Sir Philip Hampton, who officially stepped
into the role of GSK’s chairman in May 2015,
said: “Andrew’s retirement next year will represent the culmination of 32 years of service
and leadership to GSK and the industry. We
will thank Andrew more formally for his
tremendous dedication and contribution
next year. In the meantime, we will now
start a formal process to appoint his successor, whilst also ensuring the group remains
focused on execution of its strategy to drive
growth and performance.”
All formality and politeness aside, there
have almost no doubt been significant tensions in the executive offices and boardroom
from at least the time that Hampton began
heading up the board of directors. As Stephen Bailey, a fund manager at Liontrust
Asset Management Plc in London, noted in
an interview with Bloomberg in early 2015,
just before Hampton began his chairmanship, “Mr. Witty is running out of time. He’s
either got to deliver in the next 12 months
or step aside.”
“The announcement that Sir Andrew Witty
is to retire is no surprise, and if anything, may
have happened earlier. GSK has not in recent
WITTY CONTINUED ON PAGE 42
CLOUD CONTINUED ON PAGE 43
ITIF CONTINUED ON PAGE 41
Change on the way for GSK
BY JEFFREY BOULEY
LONDON—GlaxoSmithKline (GSK) is, of
course, a huge name in pharma—its CEO, Sir
Andrew Witty, is also a big name, not just for
successes that GSK enjoyed during his tenure
at the top, but also for a number of scandals
and bad press that have rocked the company
over his near-decade as CEO—among them
charges and fines for bribing doctors to prescribe GSK drugs and for marketing a number of top-selling drugs for unapproved uses.
However, many investors and other market-
Market-watchers and analysts weren’t
surprised by the upcoming retirement of CEO
Andrew Witty, but many are pleased with some
of the recent financial directions of the GSK.
In an effort to improve
the pharmacovigilance
model, they look to
comprehensive cloud
solutions to help lower
costs, raise quality
DOYLESTOWN, Pa.—Bioclinica Inc.,
a specialty clinical trials technology
and services provider, announced in
April the selection of ArisGlobal’s
Safety Cloud as the preferred safety
platform for its pharmacovigilance
services. Under this partnership, Bioclinica becomes the preferred partner
for ArisGlobal in business process
consulting and change management
as sponsors implement or upgrade
ARISg. Together, the partnership
reportedly brings a flexible delivery model that fits any organization
regardless of size or case volume.
A top-20 pharmaceutical company
has already selected Bioclinica to standardize its safety case processing service on the ArisGlobal platform, while
two other companies are making the
switch from competing platforms.
“Early adoption speaks to the
strength and value of our joint solution
in addressing industry’s long-wanted
desire for such a safety offering,” said
Bioclinica’s president of eHealth Solutions, Mukhtar Ahmed.
ArisGlobal Vice President of Safety
George Philips added: “Through our
partnership with Bioclinica, we are
able to provide the pharmaceutical
industry with an unprecedented level
of streamlined and cost-efficient endto-end pharmacovigilance services.”
The cloud-based solution replaces
traditional on-premise safety systems
unpopular with many organizations
due to burdensome management,
maintenance and fiscal challenges,
he noted, saying, “By utilizing these
services, resources within an organization can now be shifted to address
other pressing needs.”
ArisGlobal, and Bioclinica’s Safety
and Regulatory Solutions division
(formerly known as Synowledge), formulated this comprehensive partner
strategy to deliver cost-effective and
The coauthors, J. John Wu and Stephen Ezell,
ITIF vice president for global innovation policy, found that the United States, Switzerland,
Taiwan, Singapore and Sweden have enacted
CREDIT: GLAXOSMITHKLINE
BR IEFS
ITIF
policies that, on a per-GDP basis,
contribute the most to global lifesciences innovation, while India,
South Africa, Thailand, the Philippines and Australia have policies
that contribute the least.
“It is, on the one hand, understandable that policymakers tend
to focus first and foremost on the
short-term interests of their own
citizens, but too many ignore the
fact that this comes at the expense
of less innovation of new drugs,”
said Robert D. Atkinson, ITIF
president. “The bottom line is that
all nations need to do their part to
support robust global biopharma
innovation.”
This was ITIF’s first study of this
nature, says Ezell.
On the financial side, in the past
decade the United States has led
the pack in terms of government
funding, with Ezell noting that
“From 2007 to 2012, European gov-
“All nations need to do
their part to support
robust global
biopharma innovation.”
Robert D. Atkinson,
president of ITIF
ernments invested just 60 percent
the amount the U.S. government
invested in biomedical R&D expenditures, while the governments of
China, Japan, Korea, India and
Australia invested just 25 percent
as much, even though the GDP of
both regions is larger.”
“Robust federal investment in
basic scientific research in the
life sciences has long been a distinguishing feature, along with
strong intellectual property rights,
of the U.S. life-sciences innovation
ecosystem. And while the United
States has and continues to lead the
world in federal investment in basic
life-sciences research, to remain
a leader into the future, the U.S.
government should restore federal
investment in life-sciences research
to the levels attained in the early
2000s,” he remarks, adding that
“ITIF has called for Congress to
maintain NIH funding at a level
commensurate with at least one
quarter of one percent (0.25 percent) of national GDP or higher.”
According to Ezell, one U.S. policy that has significantly and positively impacted global innovation
is the 12 years of data exclusivity
protection afforded for novel biologic drugs.
“In recent years, a growing number of nations have sought to introduce policies to bolster their lifesciences sectors,” he adds. “Nations
such as the United Kingdom, Singapore, China and Sweden have
not only significantly expanded
their financial support for biomedical research, they have also
implemented a range of policies
designed to enhance their biomedical innovation ecosystems, such
as tax incentives through “patent
boxes,” regulatory reforms to speed
drug approvals and immigration
and education policies designed to
attract and to educate the best lifesciences talent.
In particular, Ezell points out,
“Singapore’s government has provided direct funding for life-sciences industry R&D, investing nearly
five times as much in the industry
as did the United States in 2009, on
a share of GDP basis.”
Ezell says innovation in the biopharmaceutical and life-sciences
industries has generally trended
upward in the past 10 years, highlighting 2014 as the best year for
the industry since 1996 in terms of
drug approvals.
“One thing to note here is that
we really only finished mapping the
human genome in the early 2000s,
and given that it takes at least a
dozen or more years for new drugs
to work their way through the devel-
opment pipeline, we really should
only be starting to see the fruits of
the Human Genome Mapping Project now. So new insights derived
from better understanding of the
human genome should put us on the
cusp of more discoveries,” says Ezell.
“Moreover, biopharma research
has started and will continue to
leverage technological advances of
the fourth industrial revolution,
such as big data analytics, supercomputers, smart manufacturing
and so forth, to improve R&D and
health outcomes. There have also
been breakthroughs in other areas,
such as personalized medicine and
gene editing. As long as countries
continue to put the right conditions in place—robust investment
in life-sciences R&D, strong intellectual property protections and drug
pricing policies that balance access
to medicines with financial returns
for innovators—we should expect to
continue to see robust rates of biomedical innovation,” he concludes. n
www.ddncancer.com
CANCER
RESEARCH
NEWS
A website
for the latest
oncology
news, trends
and resources
■
■
■
■
■
Top cancer-related news
and opinion stories
Archive of all of DDNews
cancer-related news stories
Interviews with key
oncology leaders
Links to various companies,
research centers and
organizations involved
in the field of oncology
and much more!
On the cutting edge
A roundup of
instrumentation,
software and other tools
and technology news
W
BY JEFFREY BOULEY
E DIDN’ T BRING you
any May flowers, but
how about new protein
sequencers, cloud-based
R&D, correlative RamanSEM imaging, a newly compliant handheld
Raman analyzer and cloud-based monitoring
and analysis of clinical trials?
Protein sequencers offer enhanced
sensitivity and better compliance
COLUMBIA, Md.— Shimadzu Scientific
Instruments recently released the new
PPSQ-51A single-reactor and PPSQ-53A
triple-reactor protein sequencers. The new
PPSQ-51A/53A protein sequencers employ
Shimadzu’s SPD-M30A photodiode array
detector for higher sensitivity. The detector features a capillary cell that is 8.5 times
longer than standard cells, which increases
sensitivity and enables the study of longer
protein sequences.
New PPSQ software can be configured
to meet a laboratory’s needs whether it is
regulated, research and development or academic. The software enables compliance with
FDA 21 CFR Part 11 guidelines with regard
to security, user management and audit
trail requirements. Easy-to-use data analysis
functions simplify operation, data processing and reporting. These functions allow the
reprocessing of chromatograms, the overlaying of multiple chromatograms, chromatogram subtraction and automatic estimation
of amino acid sequences. Additionally, the
PPSQ-51A/53A sequencers provide customized reports and yield graph display for a
quick and comprehensive view of data.
PPSQ series protein sequencers separate
PTH-amino acids isocratically. Isocratic
sequence analysis provides more stable
retention times. That means peaks detected
in previous cycles can be cancelled using
chromatogram subtraction, Shimadzu says,
making it easier for users to identify the correct amino acid. Performing PTH-amino acid
analysis in isocratic mode also enables laboratories to reduce liquid waste and running
costs through mobile phase recycling.
Cloud is ‘the future of R&D,’
says IDBS at Bio-IT World
BOSTON & LONDON—April 5, at the Bio
IT World Conference & Expo 2016, IDBS
signaled its commitment to delivering its
enterprise research and development (R&D)
platform in the cloud. The strategic move sees
E-WorkBook, a leading R&D platform created by scientists for scientists, available via
software-as-a-service (SaaS) for organizations
globally. According to IDBS, the “agile, adaptable SaaS offering” supports growing laboratory demands for automation, collaboration
and data sharing, as well as robust IP security.
“As the R&D landscape continues to
change rapidly, labs are increasingly realizing
the benefits the cloud can deliver, especially
with regards to reducing costs and ensuring
flexibility in an era of externalization and
collaborative partnerships,” said Laurence
Painell, vice president of product management and marketing at IDBS.
The company says it sees rapid adoption
of cloud-based services by small
and mid-tier pharmas, notes that
the majority of large enterprise
accounts are planning migration
to IDBS-hosted cloud services
over next three years and boasts
that more than 50,000 researchers and 80 percent of the top 20 pharma
firms worldwide now use IDBS software.
Rigaku complies with new Raman
calibration standards
WILMINGTON, Mass.— New regulations
came into effect recently that set acceptable
Raman wavelength shifts and associated tolerances for benchtop and handheld Raman
instruments for pharmaceutical applications.
Rigaku Analytical Devices’ Progeny 1064 nm
handheld Raman analyzer is said to be fully
compliant with the new calibration standards, which were published by the European
WITTY
BMS picks Medidata Clinical Cloud
NEW YORK—Medidata, a global provider of
cloud-based solutions for clinical research
in life sciences, announced in April that
Bristol-Myers Squibb (BMS) has selected
the Medidata Clinical Cloud to help manage,
monitor and analyze its clinical trials. Medidata’s technology platform will support BMS’
research capabilities in immuno-oncology,
oncology, immunoscience, virology, cardiovascular, fibrotic diseases, genetically modified diseases and metabolics.
The platform has been used by more than
630 customers around the world, supporting
more than 11,000 clinical studies, 420,000
investigational sites and more than 3.1 million trial volunteers, Medidata notes.
BMS will integrate Medidata’s data management, data analytics and risk-based monitoring capabilities into all stages of its drug
development process.
“Our agreement with Bristol-Myers
Squibb is a great example of how the world’s
best clinical researchers are increasingly relying on Medidata technology to help support
advances in treatments for patients,” said
Medidata’s CEO, Tarek Sherif. “Medidata
has developed the most comprehensive cloud
platform dedicated to clinical research, powered by the world’s largest data repository.
With our powerful and flexible SaaS solution, we are helping our customers achieve
meaningful time-to-market results, as well as
giving them the data and actionable insights
they need to innovate successfully.” n
years returned the results that many
investors were hoping for and, along
with its challenge in China, appears
sleepy,” says John Lyon, a professor of
practice at Warwick Business School.
“The search for a new CEO has been
afforded due time, and there is certainly a lot for a new CEO to get their
teeth into.”
Getting a bit more specific and
perhaps telegraphing what he’d like
to see Witty’s successor tackle, Lyon
continued: “Relationships between
large pharma and the outsourcing of
its medicine development through
contract research organizations has
matured in the past couple of decades
and more strategic links may be possible going forward.”
And while analysts are generally
happy with GSK at the moment, earnings-wise, the company having reported a good first quarter in its quarterly
financial report at the beginning of
May, the desire for change is clear.
Writing for Forbes about Witty’s
departure, attorney Erika Kelton bluntly stated that “Corruption, bribery, illegal marketing, contaminated drugs and
collusion are some of the ‘highlights’
of Glaxo’s business practices that were
revealed during Witty’s nine years at the
helm,” adding that the company made
headlines for all the wrong reasons
when he was in charge, and arguing
against the hiring of any internal prospects at the company to succeed him.
But, again, the news isn’t all bad.
Past problems aside and whatever
tarnish Witty’s armor may bear at the
moment, Seamus Fernandez and fellow analysts at Leerink Partners said
of the Q1 earnings: “We are encouraged by GSK’s strong 1Q sales across
its business units and geographies,”
and noted that, boosted in large part
by an improving consumer healthcare business, “GSK should deliver
on its updated FY guidance of 10 to
12 percent core EPS growth at constant exchange rates.” Leerink is particularly encouraged by the respiratory
and HIV directions at GSK right now.
Still, Fernandez and colleagues
can’t get away from Witty’s legacy and
departure, either—and there remain
some long-term concerns.
“With GSK’s base business stabilizing but a largely absent near- to medium-term pipeline, investor interest
is growing around CEO succession
plans,” they wrote in April. “In our
view, GSK’s leadership position in
consumer healthcare (CHC) and the
need to efficiently and effectively operate this business as a source of upside
suggests that at least one direction
could be toward a CEO with management expertise in CHC. Further, we
believe the mixed results coming out
of the various research ‘DPUs’ suggests
strong and more centralized R&D leadership may be necessary to drive GSK’s
culture toward one of more effective
risk-taking that includes M&A if the
company is going to deliver significant
new biopharma innovations.” n
Pharmacopeia in Supplement 8.7, Chapter
2.2.48 in October 2015.
The need to manufacture pharmaceutical
products faster and more safely combined
with the pressure to reduce the
costs and comply with rigorous
regulatory requirements has contributed to the increasing adoption of handheld Raman for raw
material identification, Rigaku
notes. The rise in popularity of
the technique resulted in the updates to
the standards for acceptable tolerances for
handheld Raman instrumentation to ensure
a set industry standard for instrument
performance.
Unlike other handheld Raman analyzers,
Progeny successfully overcomes sampleinduced fluorescence interference with the
use of a unique 1064 nm excitation laser
which also enables measurements to be taken
through packaging. The device facilitates regulatory compliance by providing a complete
IQ/OQ/PQ protocol package, compliant 21
CFR Part 11 digital signatures and an integrated camera for barcode reading to ensure
error-free data entry.
“The introduction of the new regulations
demonstrate the increased awareness and
popularity of handheld Raman as a solution
for rapid, accurate and reliable raw material identification,” commented Bree Allen,
general manager and vice president of the
Molecular business for Rigaku Analytical
Devices. “We are committed to supporting
our customers in ensuring compliance with
the new standards as well as further educating the pharmaceutical industry on the benefits handheld Raman can deliver.”
TOOLS &
TECHNOLOGY
RISE correlative microscopy
now compatible with ZEISS SEM
ULM, Germany—The WITec RISE microscopy mode for correlative Raman-SEM
(scanning electron microscopy) imaging is
now compatible with the scanning electron
microscope ZEISS MERLIN. The new hybrid
system was jointly developed by the two
German microscope manufacturers, bringing together a wealth of expertise in Raman
spectroscopic imaging and advanced ultrastructural analysis. Customers benefit from
both high-quality and sophisticated system
components for state-of-the-art research in
the fields of nanotechnology, life sciences,
geosciences, pharmaceutics, materials
research and others. The first system of this
kind was at the time of the announcement
being installed at one of the largest research
institutions in South Korea.
According to WITec, Raman microscopy—
as a label-free, non-destructive technology
for the identification and imaging of the
molecular composition of a sample—is the
perfect complement to SEM, which visualizes the surface structure of a sample, and
the often-associated EDX (energy-dispersive
X-ray spectroscopy) that can only identify
elemental constituents.
The integration of both techniques into
one system greatly improves ease of use and
accelerates the experimental workflow. It
places both the objective and sample stage
required for Raman microscopy within the
SEM’s vacuum chamber; thus, the sample
can remain under vacuum for both measurements and is simply transferred between the
Raman and SEM measuring positions by a
software-driven push-button mechanism
using an extremely precise scan stage.
“We believe that correlative RISE microscopy will be of immediate benefit in answering many scientific questions, with the integrated whole providing insight far greater
than the sum of its already exceptional parts,”
said Dr. Olaf Hollricher, CEO and director of
R&D at WITec. “The development of RISE
microscopy ... fulfills the promise of correlative microscopy for both the Raman as well
as the SEM communities.”
PFIZERGAN
newest of the anti-inversion rules: “Treasury
has taken action twice to make it harder for
companies to invert. These actions took away
some of the economic benefits of inverting
and helped slow the pace of these transactions,
but we know companies will continue to seek
new and creative ways to relocate their tax
residence to avoid paying taxes here at home.
“Today, we are announcing additional
actions to further rein in inversions and
reduce the ability of companies to avoid taxes
through earnings stripping. This will have an
important effect, but we cannot stop these
transactions without new legislation. I urge
Congress to move forward with anti-inversion
legislation this year. Ultimately, the best way
to address inversions is to reform our business
tax system, which is why Treasury is releasing
an updated framework on business tax reform,
outlining the administration’s proposals to
date as a guide for future reform. While that
work goes on, Congress should not wait to act
as inversions continue to erode our tax base.”
So what does this mean for Allergan, Pfizer
and the wider range of companies out there
considering M&As?
Well, Allergan held a conference call to
discuss its strategy and maintained that its
growth profile is the same as it ever was.
So, as Arpita Dutt pointed out in a Zacks
Investment Research note shortly after the
deal collapsed, the company—which has
about 70 mid- to late-stage programs in its
pipeline—will continue focusing on driving sales of products like Botox, Restasis,
Viibryd, Linzess and others, and it will continue to research and develop new products
like Viberzi, Kybella, Vraylar and Dalvance
to drive long-term growth.
“The company also has the divestiture of
its generics business to Teva Pharmaceutical
Industries Limited coming up in a deal slated
to close in June,” Dutt noted. “The after-tax
cash and equity proceeds of $36 billion from
the Teva transaction can be used by Allergan
to pay down debt or pursue business deals or
to buy back shares.”
As for Pfizer, speculations about the company pursuing other non-U.S. based companies had already begun while the ashes of the
Pfizergan deal were still smoldering. And, as
Dutt wrote, “at one point of time, Pfizer had
failed in its efforts to acquire AstraZeneca.
CREDIT: BUSINESSWIRE
Rumors are that Pfizer is already looking for
other big pharmas to acquire, though it is
unclear if it will do so for tax purposes or
solely to boost its pipeline and portfolio.
Currently, names of other U.K.-based firms
like GlaxoSmithKline plc are being considered as being on Pfizer’s radar. In addition to
a desire to lower its tax rate, Pfizer needs to
boost its product portfolio as well as pipeline.”
Also, still of interest to investors in Pfizer
is the actual future shape of the Big Pharma
itself, irrespective of any M&As. As Ian Read,
chairman and CEO of Pfizer, said recently,
“We [still] plan to make a decision about
whether to pursue a potential separation of
our innovative and established businesses
by no later than the end of 2016, consistent
with our original timeframe for the decision
prior to the announcement of the potential
Allergan transaction. As always, we remain
committed to enhancing shareholder value.”
And that might mean an end for now to
looking for M&A deals that would reduce taxes,
speculated Sanford C. Bernstein & Co. analyst
Timothy Anderson, saying: “The fact that the
company is talking about the original split-up
decision timeline of late 2016 almost seems
to suggest they have given up on inversion.”
Meanwhile, Sean Williams, writing at the
Motley Fool, said flatly: “Both companies will
be just fine over the long run. Most importantly, I believe shareholders can take solace
in the fact that both companies should be
just fine operating as separate entities for
many years to come,” though he did admit
that while “the two companies will put their
break-up scars in the rearview mirror pretty
quickly,” investors “may be less forgiving.”
Williams also noted that tax inversions
in the United States are as good as dead for
the short run at the very least, writing, “we
learned that the government is done beating around the bush when it comes to U.S.
companies taking advantage of tax inversion
opportunities. The new regulations all but
ensure that tax inversions of the magnitude we’ve witnessed in recent years (e.g.,
Medtronic-Covidien) are likely dead. It’s possible that smaller-case inversions may still be
sought, but the tax benefits of relocating to an
overseas market have been severely crimped.”
It wasn’t a surprise to many analysts that
the Pfizergan merger would fall apart with
the most recent rule changes, among them
John Colley, a professor of practice in the
Strategy and International Business Group of
Warwick Business School, who wrote (after
Treasury made the changes but before Pfizer
pulled the plug): “The move to limit tax inversions by the U.S. government has wiped $20
billion off the share price of Allergan, which
broadly equates to the tax benefit arising from
Pfizer merging with Allergan ... Other than
the tax benefits, it was never clear what other
benefits really existed in the deal. Pfizer does
need growth prospects and Allergan did offer
some better prospects than Pfizer, as Pfizer is
struggling for significant new drugs and has
large cash piles which cannot be repatriated
to the U.S. and shareholders for tax reasons.”
In a later statement, after Pfizergan was
history, Colley wrote: “In effect this is a major
success for the Obama administration, while
for Pfizer it is bad news as tax matters have
dominated its strategy for more than three
years,” but added on a more encouraging-yetchiding note that “Perhaps now Pfizer and
other pharmaceutical businesses can focus
on drug development rather than financial
engineering. In 2015, around $600 billion
of acquisition activity occurred in the pharmaceutical industry, a significant proportion
was driven by U.S. tax rules and avoiding tax.”
Sangeetha Prabakaran, a research manager
in Frost & Sullivan’s Transformational Health
practice, largely agrees with many of the points
both Williams and Colley made, writing: “Pfizer’s reliance on Allergan was more on the tax
sops and less Botox or Restasis sales, since Pfizer’s own breast cancer drug Ibrance has picked
up strongly. Its pipeline of hypolipidemic drugs
is strong and Pfizer needs to stay focused on
bringing the next Lipitor to market. Allergan
off-late has been more focused on Teva to hive
off its generics and reduce its debt. Allergan
may continue to scout for generics partners
while consolidating its position with Botox and
building on a strong pipeline on age-related
macular degeneration and depression.” n
EDITCONNECT
Online-only extras
Two online-only extras run on
our website this month for the
May issue: A new Q&A and a
new Patent Docs column.
Interference will
decide CRISPR
patent rights
Given the commercial potential
of CRISPR, patenting is an
obvious concern and more
than one group of inventors
has filed patent applications
on the reagents, methods
and cells produced or used,
notes DDNews columnist
Kevin Noonan. He says a U.S.
Patent Office process called
“interference” will play a key role
in sorting out patent rights. To
read it, search for Editconnect
code E051631 at www.ddnnews.com
Q&A: Geert
Cauwenbergh
The head of RXi Pharmaceuticals
tells DDNews about RNA
interference’s place in drug
discovery and development,
shares details about RXI-109 for
fibrosis and scar formation in the
skin and eye and looks to the
company’s future. To read it, do
a search for the code E051633
at www.ddn-news.com
CLOUD
regulatory-compliant services. Bioclinica’s
Global Consulting group provides organizations with business and change management
expertise when implementing or upgrading
to new versions of ARISg, including return
on investment optimization, standard operating procedure creation, system validation and
development of agile database conventions.
“The formation of this partnership addresses the full continuum of pharmacovigilance
as a service,” Ahmed remarked. “Together
Bioclinica and ArisGlobal provide the most
comprehensive solution, whether an organization wants to handle safety internally or
outsource it to our team of safety experts.”
Looking toward the next wave of innovation, the partners are already working closely
to develop ArisGlobal’s next generation of
products, which combine medical knowledge
with innovative technologies derived from
such areas as artificial intelligence, machine
CREDIT: BIOCLINICA
Bioclinica recently selected ArisGlobal’s Safety Cloud as the preferred safety platform for its
pharmacovigilance services. Pictured here is a BioClinica imaging location in Newark, Calif.
learning and natural language processing.
Bioclinica’s president of Safety and Regulatory Solutions, Sankesh Abbhi, said, “We are
creating solutions that remove the struggle
involved in assembling the required safety
reports, which can be especially difficult in
studies where therapies carry intense safety
monitoring requirements. ArisGlobal currently has an extraordinarily high customer
satisfaction rating, and our investment in
innovation and automation demonstrates, in
return, our commitment to our customers.”
ArisGlobal’s cloud-based solutions facilitate global drug development and regulatory compliance within the life-sciences
and healthcare industries. Its cloud platform supports the entire product life cycle,
including clinical development, regulatory affairs, pharmacovigilance and medical
communications.
Bioclinica is a specialty services provider
that utilizes expertise and technology to
create clarity in the clinical trial process.
Bioclinica is organized by separate business
segments to deliver focused service supporting multifaceted technologies. The Medical
Imaging and Biomarkers segment provides
medical imaging and cardiac safety services
and includes a molecular marker laboratory.
The eHealth Solutions segment comprises
the eClinical Solutions platform, Clinverse
Financial Lifecycle Solutions, Safety and
Regulatory Solutions, Strategic Consulting
Services, App xChange Alliances and eHealth
Cloud Services. n
AWARDS & HONORS
Awards & Honors
SANTA CLARA, Calif.—Late
April saw Agilent
Technologies Inc. announce that it had bestowed
an Agilent Thought Leader Award on Dr. Shilin
Chen in support of his groundbreaking herbal
genomics research using multiomics techniques.
Chen directs the Institute of Chinese Materia
Medica at the China Academy of Chinese Medical
Sciences in Beijing. The institute strives to identify the active ingredients in traditional Chinese
medicines and make new drugs.
The award will fund the use of integrated biology—including various multiomic solutions from
Agilent—to generate important biological data sets
related to the biosynthesis of bioactive compounds
from herbs, artemisinin and glycyrrhizin among them.
Through his research, Chen hopes to deepen
understanding of the mechanism by which herbal
medicines disrupt diseases and identify relevant
biomarkers, which could then point the way to
new drug discovery.
AIME takes top honors in Pistoia
Alliance Mini Start Up Challenge
WILMINGTON, Del.—AIME
has won the inaugural
Pistoia Alliance Mini Start-Up Challenge following
a closely fought contest. Alongside this, xRapid
was also voted as the audience winner at the
Pistoia Alliance European conference in London.
The Pistoia Alliance, an organization dedicated
to improving global life-sciences research and
development, established the challenge to support innovative new start-ups with the potential
to improve life-sciences R&D.
AIME was announced the winner of the overall
contest and will receive a prize of €10,000 and
three months mentorship from a senior member
of the Pistoia Alliance. Meanwhile, xRapid, the
winner of the audience vote, will receive $5,000
while the other finalists will each receive $1,000.
AIME, a mobile app, can be used to predict disease outbreaks three months in advance using artificial intelligence, epidemiology and public health
expertise. The app is currently at 88.62-percent
accuracy, and can be used to provide information
to public health officers, saving lives and money,
the Pistoia Alliance says.
“It is time we revolutionize public health by
moving from a reactive approach to a proactive
one. It’s time we stop deadly outbreaks in advance
and save more lives,” said Dr. Dhesi Raja of AIME,
upon receiving the award. “Today, the Pistoia
Alliance demonstrated that the path towards better
health resides in preventive medicine, validating
our motto of ‘Predicting Diseases, Saving Lives.’”
For their part, the people at xRapid are developing
a digital diagnostic test for tuberculosis. Current
diagnostic techniques take up to six weeks, but
using a combination of digital image processing
and artificial intelligence, the xRapid mobile app
aims to be able to diagnose tuberculosis quicker
and more cheaply—and as accurately as an expert
microscopist.
Jean Viry-Babel, CEO of xRapid, said: “At xRapid, we are thrilled to have won the public vote.
We are pleased that the members of the Pistoia
Alliance were able to see the potential of the
XRapid Automated Diagnostic App. This event has
been a great platform to showcase our innovative
technology in front of the pharmaceutical industry.”
“We are delighted to receive an Agilent Thought
Leader Award. It will allow us to incorporate
integrated experimental and bioinformatics
approaches to traditional Chinese medicine,”
said Chen. “Our group is focusing on dissecting
and understanding the biosynthesis and regulatory
mechanisms responsible for specific metabolic
processes generated by natural herbs. We have
initiated the herbal genomic project, and Agilent’s
innovative technologies and unique solutions
can provide new tools and approaches to help
us combine metabolomics and genomics in the
study of traditional Chinese medicine. We are
looking forward to working collaboratively with
Agilent scientists to accelerate the discovery and
characterization of new medicines.”
“We are pleased to support Dr. Chen’s efforts
in the systems-level analysis of herbal metabolic
processes using integrated omics approaches,”
said Dr. Teng Chai Hock, vice president and general
“Supporting start-up companies is a crucial
component of the Pistoia Alliance’s future strategy.
Start-ups are one of the best sources for innovation,
and I am delighted to say our finalists this year did
not disappoint,” said Steve Arlington, president of
the Pistoia Alliance. “We have had an incredible
range of companies enter, with new techniques in
medicine, research, public health and agriculture
all competing.”
Exco InTouch wins at
Northern Tech Awards
NOTTINGHAM, U.K.—Exco InTouch, a provider
of digital patient engagement and data capture
solutions for clinical research and healthcare
providers, was in late March recognized as the
sixth-fastest growing technology company in the
North of England and Scotland in the 2016 Northern
Tech Awards. Exco InTouch was also presented
with the Judges’ Award for International Success.
The award ceremony took place at the Titanic
Hotel in Liverpool with the “Top-50 Fastest Growing
Technology Companies” ranked by revenue growth
over the last three years. Tim Davis, CEO and
founder of Exco InTouch, was asked to present to
the panel of judges, which included Sir Terry Leahy,
former CEO of Tesco, and Richard Faulkner, head
of technology, media and telecoms at Barclays.
Out of the 50 companies, only five were selected
for a special Judges’ Award.
Commenting on securing the accolade, Davis
remarked: “We are honored to have won this award
in recognition of our continued high growth and
international achievement and are proud to be
making a strong and sustained contribution towards
the North’s business success story. Indeed, our
sales have more than tripled over the course of
the last three years, and since then, we have seen
revenues continue to advance rapidly into 2016.”
“Innovation in our field lies at the heart of our
success,” he continued. “Our robust offering has
led to modernization and optimized performance in
patient engagement and data capture solutions for
global clinical trials and digital health programs.
We have established strong partnerships with
pharmaceutical companies both in the U.S. and
throughout Europe and have taken full advantage of
the rapid expansion and demand for technological
CREDIT: AGILENT TECHNOLOGIES
Agilent gives out an honor...and gets one, too
Agilent recently honored a Chinese
researcher for his work in identifying active
ingredients in traditional Chinese medicines
to make new drugs, and itself was honored
for outstanding customer service.
manager of Agilent’s Life Sciences and Applied
Markets Group in Greater China. “Dr. Chen’s
research is a prime example of continued innovation in traditional Chinese medicine through the
application of advanced analytical methods.”
The Agilent Thought Leader Award promotes
solutions in these clinical and healthcare markets.
Consequently, we look forward with confidence to
sustaining the exponential growth that we have
secured to date.”
Sarcoma foundation honors
Advaxis for advancements in
immunotherapy
PRINCETON, N.J.—Advaxis
Inc., a clinical-stage
biotechnology company developing cancer immunotherapies, announced in mid-April that the
Sarcoma Foundation of America had awarded
Advaxis the 2016 Vision of Hope Award for the
company’s efforts to advance an immunotherapy
platform to fight osteosarcoma.
“The Sarcoma Foundation of America is proud
to present the Vision of Hope Award to Advaxis
Immunotherapies, a trailblazer in the osteosarcoma space,” said Dr. Bert Thomas IV, CEO of the
Sarcoma Foundation of America. “Their innovative
technology gives hope to sarcoma patients in
critical need of new treatments and paves the way
for additional immunotherapies to offer patients
a brighter future.”
Advaxis is the first biotechnology company to
ever receive the award, and was so honored for
its work in the development of ADXS-HER2, an
Lm Technology that has received an Orphan Drug
designation from the FDA and EMA for treatment of
osteosarcoma. In a study examining canine osteosarcoma, 18 dogs received either 2x108, 5x108, 1x109
or 3.3x109 CFU of ADXS–HER2 post-completion of
surgery and adjuvant chemotherapy, with 15 dogs
showing an induced antigen-specific response
within six months of immunotherapy administration.
Additionally, treatment with ADXS-HER2 reduced
the incidence of metastatic disease and prolonged
survival relative to a historical control group with
only low-grade, transient side effects.
Osteosarcoma is the most common bone cancer
in children and teens. It is the third-most common
cancer in teens alone after lymphomas and brain
tumors. HER2 is expressed in approximately 40
to 60 percent of pediatric osteosarcomas and in
pulmonary metastatic disease, providing a strong
rationale for HER2-targeted immunotherapy in
these cancers.
“We are honored to be chosen as a recipi-
fundamental scientific advances by contributing
financial support, products and expertise to the
research of influential thought leaders in the life sciences, diagnostics and applied chemical markets.
A little over a month earlier, Agilent itself was
honored, receiving the 2016 Reviewers’ Choice
Award for Customer Service from SelectScience, an
independent, expert-led scientific review. This is the
second year in a row Agilent has been so honored
by the group for outstanding customer service.
“Our customers’ opinions are our greatest
measure of success,” said Doug McDougall,
vice president and general manager, Agilent
CrossLab Services and Support Division. “It’s
an honor to have customers cast their vote for
Agilent. Our focus is to continue to deliver the
insights customers need to achieve even better
outcomes in their labs. This award tells us our
commitment to this mission is making a real difference for our customers.” n
ent of this prestigious Award from the Sarcoma
Foundation of America,” said Daniel J. O’Connor,
president and CEO of Advaxis. “We recognize the
serious unmet need to treat children and young
adults battling this life-threatening disease and are
proud to work towards developing immunotherapies
that may help change the course of osteosarcoma
patients’ lives.”
Clinical microbiology and
infectious diseases contribution
recognized at ECCMID
AMSTERDAM—The
European Society of Clinical
Microbiology and Infectious Diseases (ESCMID)
announced the winner of its 2016 excellence award
at its annual congress, the 26th European Congress
of Clinical Microbiology and Infectious Diseases
(ECCMID) in April.
Prof. Robert A. Bonomo, chief of medical service at the Cleveland Veteran Affairs Medical
Center in Ohio, director of the Geriatric Research
Education & Clinical Center of the Veterans
Integrated Service Network, co-chair of the GramNegative Committee of the Antibiotic Resistance
Leadership Group and vice chairman of veterans
affairs of University Hospitals Case Medical Center,
received the ESCMID Award for Excellence in
Clinical Microbiology and Infectious Diseases 2016.
This award is the most prestigious prize given at
the annual congress each year and recognizes
an outstanding lifetime contribution to the field
of antimicrobial resistance.
Bonomo is being recognized by ESCMID for
his research, teaching, mentoring and over 340
publications, all of which have greatly enhanced
science, particularly in the field of antibiotic
resistance. His primary research efforts focus
on structure-function relationships of clinically
important beta-lactamases using microbiological
and biochemical testing, medicinal chemistry,
structural biology, pharmacological analyses,
genetics and molecular epidemiology. Bonomo
and his team have participated in the evaluation
of many preclinical and clinical drug candidates,
including the testing of four novel antimicrobial
agents which progressed to Phase 3 clinical trials and won regulatory approval, as well as over
100 other beta-lactamase inhibitor candidates. n
F E AT U R E D P R O D U C T
PRODUCTS & SERVICES
Quick volume
adjustment pipette
ADVERTISER ’S INDEX
INTEGRA Biosciences
CellSimple Cell Analyzer:
Benchtop cellular analysis on demand
Cell Signaling Technology
Complex cell- and
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instrument relies on
disposable cassettes
for sample handling, which alleviates the need for flow cell cleaning and
fluidics maintenance. And, the instrument is small enough to be portable
between the lab bench and the hood.
Cell Signaling Technology
www.cellsignal.com/CS
New uniflow fume
hood catalog
HEMCO
Features the
AireStream
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hoods (“SE,”
“LE,” and “CE”
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HEMCO
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BaseSpace informatics suite
to accelerate genomic data
analysis for sequence labs
Illumina
Inc.
BaseSpace
Suite is the most
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Illumina Inc.
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Unlike traditional
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INTEGRA Biosciences
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American Society for Cell Biology (ASCB)..........35 www.ascb.org
Asterand Bioscience.................................................21 www.asterand.com
Bio-Rad Laboratories, Inc.........................................48 www.bio-rad.com
BioTek Instruments, Inc............................................19 www.biotek.com
Cambridge Healthtech Institute..............................33 www.healthtech.com
Cayman Chemical Co.................................................31 www.caymanchem.com
Cell Signaling Technology, Inc................................23 www.cellsignal.com
ChemBridge Corporation..........................................17 www.chembridge.com
Cisbio US, Inc................................................................ 7 www.cisbio.com
Eppendorf North America........................................... 5 www.eppendorf.com
INDIGO Biosciences..................................................29 www.indigobiosciences.com
MTI-GlobalStem............................................................ 9 www.mti-globalstem.com
Offenberger & White, Inc..........................................39 www.offwhite.com
OriGene Technologies, Inc................................ Cover www.origene.com
PerkinElmer Corporation............................................ 2 www.perkinelmer.com
R&D Systems, Inc.......................................................15 www.RnDSystems.com
Seahorse Bioscience................................................25 www.seahorsebio.com
New system allows
label-free, long time course,
live-cell imaging
New high-throughput platform
for immuno-oncology research
Phasefocus
Introducing
Livecyte, a
new complete
live-cell
imaging system for kinetic cytometry.
This product will enable cell biology
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plates, this intuitive system delivers
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Phasefocus
www.phasefocus.com
Horizon
Discovery has
introduced a
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for immunooncology
research.
The platform consists of several
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increase their ability to kill tumors.
The platform includes high-throughput
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Horizon Discovery
www.horizondiscovery.com
New 2X At Taq Master Mix
SmartCapture Technology
Vivantis
Aplegen
The new 2X
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Vivantis
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SmartCapture
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This can all be set up as a protocol
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Aplegen offers a range of gel
documentation systems including the
Omega Fluor and the Omega Lum series.
All have a range of exciting features
and high specifications but at prices to
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Aplegen
www.gelcompany.com
A new range of
non-human FISH probes
Horizon Discovery
Oxford
Gene
Technology
The probes
were developed
as part of an
Innovate UK
knowledge transfer partnershipfunded project in collaboration with
the University of Kent. The probes use
proprietary Chromoprobe technology
which effectively simplifies the
fluorescence in-situ hybridization (FISH)
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Oxford Gene Technology
www.cytocell.com
Bio-Rad expands ddPCR
multiplex mutation
screening kit portfolio for
cancer research
High-speed closed tube sorter
HCTS2000 MK2
Advanced genomics and
cancer research, drug
development and NGS
Sarstedt Inc.
Formerly
from m-u-t,
the Sarstedt
HCTS2000 MK2
accessions and
sorts closed
primary sample tubes rapidly and
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bins. Optional extension modules add
five bins each for up to 22 targets. The
instrument can process up to 2,000
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Users can select 10 different sets of
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It is compatible with a broad range of
tubes, regardless of manufacturer.
Sarstedt Inc.
(800) 257-5101
www.sarstedt.com
Bio-Rad Laboratories Inc.
Bio-Rad Laboratories Inc. has
launched five new ddPCR Mutliplex
Mutation Screening Kits. The kits
screen for multiple key actionable
cancer mutations and wild type in a
single reaction from both formalinfixed, paraffin-embedded (FFPE) and
liquid biopsy sources. The new ddPCR
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detect mutations in BRAF, KRAS and
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ovarian, thyroid, melanoma, breast and
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Bio-Rad Laboratories Inc.
http://www.bio-rad.com/en-us/product/
digital-pcr-assays?tab=Kits+%26+Reag
ents&source_wt=MultiplexKits_surl
PerkinElmer Inc.
Using PerkinElmer’s LabChip platform
and the NGS 3K assay, researchers
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which is especially important for rare
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sequencing is not an option. The
technology is designed to save time
and allows for enhanced data analysis
for simplified archiving and sharing.
The NGS 3K assay provides a highthroughput means to measure smear
and fragment size distribution within the
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PerkinElmer Inc.
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LATE-BREAKING NEWS
Late-Breaking News
NEWS ITEMS THAT ARRIVED TOWARD THE TAIL END OF THIS ISSUE’S PLANNING AND PRODUCTION PROCESS
A tale of two deals for Abbott: Alere and St. Jude
BY JEFFREY BOULEY
ABBOTT PARK, Ill.—April 28 was
probably what one might call a
“weird day” for Abbott Laboratories. Here it was, announcing a
$25-billion deal to acquire Minnesota-based St. Jude Medical so that
it could gain ground in high-growth
cardiovascular markets, including
atrial fibrillation and neuromodulation...then Alere let the cat out of
the bag later that day that Abbott
had attempted to terminate its
pending $5.8-billion merger deal
with Alere—and that Alere’s board
promptly rejected that idea and
the proposed termination fee of as
much as $50 million.
Since the Alere deal was first in
line, let’s tackle that first to give you
some perspective.
First off, while Abbott seems to
have lined up financing with an eye
toward going through with both
deals, it seems to be less than smitten with Alere lately. In an April 20
Q1 earnings call with investors and
analysts, Abbott had a distinctly
noncommittal tone about the Alere
deal even before the revelation
eight days later that it had actually
tried to end the merger plans.
Why? Well, it hasn’t helped that
Alere has delayed filing its earnings
report twice, which lead Abbott to
inform the company’s board that
“it has serious concerns about,
among other things, the accuracy
of various representations, warranties and covenants made by Alere
CREDIT: ABBOTT LABORATORIES
Abbott may be stuck buying diagnostic
player Alere, even as it finances a deal to
acquire St. Jude for CVD devices
Abbott is in the process of deals to acquire both Alere and St. Jude Medical,
for point-of-care testing and cardiovascular disease treating devices,
respectively—both deals totaling more than $30 billion in value combined.
call—”I’m going to be careful how
I answer any questions about Alere,
because as you know they’ve had
delays filing their 10-K. We don’t
know when they will file their
proxy. We don’t know when they
are going to have a shareholder
in the parties’ merger agreement.”
Among those concerns are government investigations involving Alere
over its sales practices.
Abbott CEO Miles White’s uninspiring comments regarding Alere
during his company’s Q1 earnings
vote. So right now I’d say it’s not
appropriate for me to comment on
Alere.”
Alere has said that it is confident that “there is no basis for the
termination of the merger agreement” and expects the deal to be
completed according to its terms.
It also noted that it had received
approval from its lenders for an
extension to file its annual report
pending an accounting review.
However, that may not be all the
lenders—one or more may have
filed default notices, according to
certain sources.
Alere was very much in need of
a financial lifeline when Abbott
came around, so its motivations for
keeping the deal alive are clear. For
Abbott, the appeal of the merger
seems largely to give it a stronger
foothold in point-of-care testing—
Alere makes tests for infections
ABBOTT CONTINUED ON PAGE 47
TSRI scientists reveal secrets of a deadly virus family
LA JOLLA, Calif.—For the first time,
scientists at The Scripps Research
Institute (TSRI) have solved the
structure of the biological machinery used by a common virus to recognize and attack human host cells.
Their findings were published April
25, 2016, in the journal Nature
Structural & Molecular Biology.
The new structure gives scientists the first view of the glycoprotein of lymphocytic choriomeningitis virus (LCMV), a virus present on
every continent except Antarctica.
Not only does the research reveal
important traits in LCMV, it also
points to possible drug targets on
LCMV’s close relative: Lassa virus.
“LCMV has been a beacon that
has illuminated immunology and
virology for decades,” said Erica
Ollmann Saphire, a TSRI professor.
“This structure provides the missing roadmap to understand how to
defend against its extremely lethal
cousin, Lassa virus.”
LCMV is a rodent-borne virus
that rarely causes noticeable symptoms in people, although it can
progress to cause dangerous swelling in the brain and spinal cord of
immunocompromised patients and
birth defects when contracted during pregnancy.
Over the years, the virus has
served as a tool for understanding how the body responds to viral
infections. “LCMV was the experimental virus that has illuminated
much of what we understand about
immunology and virology,” said
Saphire.
Another TSRI professor, Michael
Oldstone, co-author of the new
study, did much of the foundational
work on LCMV and has long recognized LCMV’s similarity to Lassa
virus, which looks identical under
an electron microscope and shares
65 percent identity in the glycoprotein gene. Lassa is a much more
deadly disease, however, causing
thousands of deaths every year.
While LCMV is a critical
research tool, in the past 80 years
scientists have been missing an
important piece of the puzzle: a
structural understanding of the
proteins LCMV uses to initiate
infection.
Solving that structure took 10
years and has led to interesting
insights into members of the arenavirus family—and how to stop
them.
For the study, researchers in
Saphire’s lab used X-ray crystallography to build three-dimensional
models of the viral machinery,
called the surface glycoprotein,
CREDIT: TSRI
Findings could guide development of
treatments for Lassa fever
A new structure revealed by TSRI
researchers gives scientists a new
view of lymphocytic choriomeningitis
virus, which is present on every
continent except Antarctica.
which LCMV uses to fuse with host
cells. Building the models required
the scientists to screen hundreds of
crystals until they found one that
was stable enough to yield the necessary data.
When the team finally solved the
structure, it showed that the surface
glycoprotein is made up of a twopart “dimer.” The dimer is made of
two identical complexes that point
opposite directions—”It’s like a yin
and yang,” said Saphire.
Two protein subunits make
up each complex. One subunit,
termed GP1, attaches onto the cell
to be infected. The other subunit,
called GP2, serves as the infection
machinery, launching the process by which the virus fuses into
the cell and hijacks it for its own
purposes.
The researchers compared each
complex to an ice cream cone: GP1
forms the scoop of ice cream and
GP2 forms a cone that cradles the
scoop. Then there’s a long drip (the
N-terminal strand of GP1) running
down the side of the cone.
“This structure is extremely
important scientifically because
it’s the first pre-fusion structure for
any arenavirus glycoprotein,” said
a TSRI senior research associate,
Kathryn Hastie, who was co-first
author of the study with Sébastien
Igonet, formerly of TSRI, now at
CALIXAR.
The new view of the virus came
with some surprises. For one thing,
the dimer suggested that LCMV’s
structure is a sort of “missing link”
between two classes of viruses.
Class I viruses, such as HIV, have
a three-part “trimer” structure
forming their fusion machinery,
while class II viruses, such as dengue, have a more rounded protein
coat covering the whole virus.
LCMV’s dimer lies flat, like class
II proteins, but it likely brings in a
third subunit later, creating a class
I-like trimer.
“It has moving parts,” explained
Saphire. She added that LCMV
now looks like it sits between class
I and class II viruses, making this
structure a possible “fossil” of an
intermediate evolutionary process.
In work spearheaded by TSRI
biologist Brian Sullivan, the
researchers studied how LCMV
assembles and interacts with cells.
By adding individual mutations to
the genes for LCMV’s surface glycoprotein, the researchers identified
five protein “residues” necessary
for the virus to bind to host cells.
These experiments also showed
that, although the dimer is just a
stage in the LCMV life cycle, it is a
particularly critical stage. Disruption of the dimeric structure prevents viral growth.
The researchers said these findings shed light on how this viral
machine moves and rotates during
infection, an action that could be
blocked by drugs and antibodies.
The new study also raises questions as to the degree of similarity
between Lassa and LCMV. Could
the dimer structure be particular
to LCMV or is it a shared feature?
“That information, and the fold
of the GP1-GP2 complex, will be
critical in the design of antibody
cocktails for the treatment of Lassa
fever,” said Hastie. n
LATE-BREAKING NEWS
Merck KGaA (pictured here)
believes that Unisys’ approach to
global IT services for the company
will allow it to significantly reduce
the number of service providers
and gain a much better overview of
end-user IT infrastructure, services
and performance.
pharmaceutical industry, its wealth of
experience in delivering global transformation projects and its service delivery capabilities, Unisys is an obvious
partner for us,” said Dr. David Revish,
global head of vendor management,
end-user services and service integration at Merck KGaA. “Unisys’ approach
will allow us to significantly reduce the
number of service providers and gain a
much better overview of our end-user
IT infrastructure, services and performance. Ultimately Unisys will support us
in becoming a more efficient, productive,
end-user-centered service organization.”
Sanofi still looking to
acquire Medivation
PARIS—Sanofi revealed April 28
that it had made an offer to acquire
Medivation for $52.50 per share in cash,
or approximately $9.3 billion, as part of
the company’s strategy to rebuild its
oncology franchise—the offer, however,
was promptly rejected soon after the
announcement. The very next day, Sanofi
reiterated its commitment to consummating the transaction.
The company stated: “Combining
Sanofi and Medivation represents a compelling strategic and financial opportunity
to drive immediate and certain value
for Medivation’s shareholders while
benefiting patients and both companies’
respective stakeholders. Sanofi’s all-cash
proposal represents over a 50-percent
premium to Medivation’s two-month
volume weighted average trading price
prior to takeover rumors.
“Sanofi is a disciplined acquirer and
has a strong acquisition track-record.
While to date Medivation has chosen
ABBOTT
such as HIV, tuberculosis, malaria and
dengue.
So, it’s entirely possible the deal might
yet go through and that Abbott may not
have a compelling reason—or a convincing excuse—to back out.
Leerink Partners analysts Dan Leonard, Kevin Chen and Michael Sarcone
had this take on the situation with Alere
(ALR) and Abbott (ABT): “There is a never
a dull moment with this stock. We think
the lender process manageable, but the
stakes heightened in the ABT/ALR story
otherwise. If ABT no longer feels ALR the
‘perfect fit’ for its business, it could press
the Department of Justice investigation
and 10-K delay in a Material Adverse Event
clause argument in court. ALR can defend,
assuming the historical revisions are imma-
not to enter into discussions regarding
this value-creating transaction, Sanofi
remains committed to the combination
and looks forward to engaging directly
with Medivation shareholders with
regard to our proposal.”
Medivation currently markets Xtandi
(enzalutamide), which is approved in the
United States and Europe for metastatic
castration-resistant prostate cancer, a
product it markets in collaboration with
Astellas. Medivation also has two other
oncology drugs in clinical development:
pidilizumab for hematologic cancers and
talazoparib for breast cancer.
The rejection wasn’t a surprise to
Canaccord biotechnology analyst John
CREDIT: SANOFI
LONDON—Unisys Corp. announced in
late April that its subsidiary in Germany
has won a new five-year contract to
provide Merck KGaA with end-user IT
services for its 48,000 employees worldwide. Under the new contract, Unisys
will provide the global pharmaceutical,
chemical and life-sciences company
with global service desk, unified endpoint management and on-site services.
Merck has made acquisitions and
divestitures totaling €38 billion (S$42
billion) in the past decade, including
its latest acquisition of Sigma-Aldrich
in November 2015. In order to continue
on this growth trajectory, the company
needs to provide the scalability and flexibility in end-user IT services required
to keep employees as productive as
possible, the companies note.
Unisys will provide Merck with a global
service desk spanning 90 countries, with
Unisys professionals managing all service
requests and incidents in 11 languages.
Unisys will also deliver global field services
across all 90 countries to handle requests
that cannot be resolved remotely, assist
technology rollouts and provide additional
service lines and support to company
leadership and senior executives.
The solution for Merck follows Unisys’
People Computing approach, which is
a user-friendly approach that provides
a client’s employees with the tools they
need to be successful in their jobs. As
part of this approach, Unisys will deliver
personalized end-user services tailored
to each employee’s “persona,” a profile
tied to the individual’s specific role within
the organization. Structuring the service
model in this way gives each employee
the specific support they need to improve
availability of the technology they rely on
daily and enjoy the most consistent, satisfactory end-user experience possible.
Unisys also plans to provide walk-in
kiosks to amplify the cost savings and
operational efficiencies that its unified
end-point management is designed to
deliver. Based on a self-help approach,
the kiosks are intended to enable Merck
users to receive software help, swap
hardware, request education and training
and test new devices without making an
appointment.
“With its strong knowledge of the
CREDIT: ARMIN KÜBELBECK_CC BY-SA 3.0
Merck KGaA selects Unisys
for global end-user IT services
Sanofi made a play for Medivation
to give new life to its oncology
portfolio, but the initial $9.3-billion
offer was rejected.
Newman, who wrote in a note to investors right after the Sanofi announcement:
“We believe Sanofi’s $52.50 offer for
MDVN shares is likely to be pushed
higher, especially as we see near-term
value drivers in prostate and breast
cancer for Xtandi. Sanofi utilized the
weakness in the overall biotech sector
and NASDAQ to offer a ‘premium of over
50% to the two- month volume weighted
average price’ in a letter sent to MDVN
on April 15. Medivation is concluding a
meeting regarding Sanofi’s proposal,
which we expect will be rejected today.”
As it turns out, he was right, and we
shall see whether further negotiations
and actions bear fruit for Sanofi or bring
out rival bids.
Hunting for medicines
targeting rare diseases
PALO ALTO, Calif.—On April 28, twoXAR
Inc., a company dedicated to improving
health through computation, announced
a collaboration with Dr. Joyce Teng of the
Department of Dermatology at Stanford
University to support research focused
on the identification of drug candidates
targeting rare disorders such as lymphatic malformation and epidermolysis
terial. ALR’s stock will trade off on this
news of course, but we continue to believe
the odds of Abbott’s (ABT, MP) consummation of its proposed acquisition of ALR
are overly discounted in the market, and
think the upside outweighs the downside.”
Meanwhile, we have what Abbott is
calling on its website its “next big step”
in the notion that combining cardiovascular disease (CVD) device company St.
Jude Medical with Abbott, which itself is
a major player in vascular care with stents,
related products and mitral valve repair,
“will result in one of the world’s premier
medical-device companies.”
St. Jude is focused on several key areas
in medical devices: heart failure, arrhythmias, vascular disease, structural heart and
chronic pain. Its product portfolio is highly
complementary, according to Abbott, and
brings Abbott leading positions in areas
bullosa simplex (EBS). As part of this
collaboration, twoXAR will help fund
some of the collection and analysis of
disease-specific gene expression data,
which will be made available to the global
research community and used to power
disease-to-candidate predictions using
the company’s discovery platform.
Teng, director of pediatric dermatology, is leading research aimed at improving treatment options and care outcomes
for rare diseases. A significant challenge
faced by the rare disease community
is access to sufficient data to power
meaningful investigations into disease
mechanisms and new therapies. Through
their study of diseases like lymphatic
malformation and EBS, Teng’s team will
compile the most comprehensive compendiums of biomedical data available
for these disorders.
“As is the case with many rare diseases, EBS and lymphatic malformation
have no FDA-approved medications
and our best current treatment options
consist of supportive care or surgeries
to improve symptoms,” said Teng. “We
are pleased to be working with twoXAR
in this preclinical study collaboration
as we strive to change the outcome
for people living with rare and often
incredibly painful and disabling diseases
like lymphatic malformation and EBS.”
In its work, twoXAR has developed
patent-pending algorithms that it says
enable it to find unanticipated associations between disease and drug
candidates orders of magnitudes faster
than wet lab-based approaches. The
company’s integrative biomedical software platform rapidly evaluates massive public and proprietary datasets
to identify and rank high probability
disease-to-candidate matches. These
matches can then be used to prioritize
existing candidates, perform targeted
searches and identify novel drug candidates for further preclinical and clinical
testing. The platform is disease-agnostic
and has been tested on more than 40
conditions to date.
“This is an exciting opportunity to
support patients and demonstrate how
our technology can be used to identify potential new treatments faster
and more cost-effectively than previous approaches,” said Andrew A.
Radin, co-founder and CEO of twoXAR.
such as atrial fibrillation, cardiac rhythm
management and heart failure, among
other cardiovascular and neurological
specialties.
Abbott notes that CVD is one of the
most important health challenges worldwide, and that St. Jude brings strengths
across the spectrum of cardiovascular care
technologies.
“Bringing together these two great companies will create a premier medical device
business and immediately advance Abbott’s
strategic and competitive position,” said
White. “The combined business will have
a powerful pipeline ready to deliver nextgeneration medical technologies and offer
improved efficiencies for healthcare systems around the world.”
As Frost & Sullivan analyst Venkat Rajan
notes: “Abbott’s $25-billion acquisition of
St. Jude Medical continues a recent indus-
“Through our work with Dr. Teng, we
hope to develop additional expertise
that will pave the way for investigating
treatments using novel bioinformatics
approaches for orphan diseases with
unmet needs.”
PacBio and
Advanced Analytical
Technologies announce
co-marketing agreement
MENLO PARK, Calif. & ANKENY, Iowa—
Late April saw Pacific Biosciences of
California Inc. (PacBio) and Advanced
Analytical Technologies Inc. (AATI)
announce an agreement to jointly promote their technology solutions for longread DNA sequencing.
The PacBio RS II and Sequel Systems
are based on PacBio’s proven Single
Molecule, Real-Time (SMRT) technology and are used to sequence small or
large genomes, as well as to perform
targeted sequencing, complex population
analysis and RNA sequencing. SMRT
sequencing provides characterization
of many types of genomic variation,
including those in complex regions not
accessible with short-read or synthetic
long-read sequencing technologies. It
also reveals epigenetic information.
AATI’s Fragment Analyzer quantifies
and qualifies nucleic acid samples in
one step with accurate sizing to ~50
kilobases in length. The method takes
~1 hour (as opposed to ~16 hours with
pulse field gel electrophoresis) and can
process up to 96 samples in parallel.
“We are excited to team with Advanced
Analytical. Their Fragment Analyzer will
help streamline our large-insert library
workflow for de-novo assemblies, where
it is important to know the size of the
libraries before and after size selection,”
said Kevin Corcoran, senior vice president
of market development at PacBio. “Use
of the Fragment Analyzer for accurate
sizing will significantly speed the time it
takes to make a library and improve the
likelihood of project success.”
Dr. Jonathan Hagopian, director of
business development at AATI, added:
“We are proud that we have met PacBio’s
high standards for data quality and performance with our Fragment Analyzer
system. Our collaboration will accelerate
discoveries based on their powerful
long-read sequencing technology.” n
try trend of mega-mergers and consolidation. The combined cardiovascular product
portfolio of both organizations positions
Abbott as one of the most comprehensive
medical technology solution providers
for all types of cardiovascular diseases. By
virtue of St. Jude Medical’s acquisition of
left ventricular assist device manufacturer
Thoratec in 2015, Abbott now has access
to a billion-dollar treatment segment that
even cardiovascular device market leader
Medtronic doesn’t participate in.”
Leerink Partners analysts Danielle Antalffy and Puneet Souda called the Abbott-St.
Jude deal “a strategically positive acquisition” and predicted it would be immediately accretive to Abbott, whose “device
business has been under-scaled, driving
underperformance over the last few years
vs. the mid-single-digit growth of the broader [medical technology] market.” n
BIO-RAD’S DROPLET DIGITAL™ PCR SYSTEMS
Over 400 Peer-Reviewed Droplet Digital PCR (ddPCR™ ) Publications*
From detection of rare mutations and cancer biomarkers to quantification of gene editing events
and miniscule viral loads, the QX100™ and QX200™ Droplet Digital PCR Systems have been used to
redefine the limits of absolute nucleic acid quantification. With over 400 peer-reviewed publications,
ddPCR platforms have outperformed other digital PCR systems by several orders of magnitude. The
third-generation QX200™ AutoDG™ System now brings automation and scalability to digital PCR.
Visit bio-rad.com/info/400DDN for the publication list and to learn more.
* Based on PubMed data, March 2016.
16-0228_DBC_ddPCR_400Pub_DDN_050116_FINAL.indd 1
3/30/16 3:52 PM

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