BioCentury Curing cancer trials Product Discovery & Development BioCentury This Week

Transcription

WEEK OF FEBRUARY 28, 2011
BioCentury
THE
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EPORT ON
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IOB USINESS
Volume 19 Number 10 Page A1 of 20
Product Discovery & Development
Curing cancer trials
BioCentury This Week
Cover Story
Emerging Company Profile
Curing Cancer Trials — NCI’s Clinical
Trials Cooperative Groups Program is said to
be “approaching a state of crisis.” But if
there is broad agreement it must be fixed,
the means for overhauling the system are
controversial.
Shushing the Usher — Karyopharm thinks its
molecules that block removal of tumor suppressor proteins and growth regulatory proteins
from the nucleus will target cancer cells without
the risk of tumor resistance./A12
Understanding the Co-ops — IOM's
warning about NCI's Clinical Trials Cooperative Program was not the first, as similar red
flags were raised in 1997 about the system,
which comprises 3,100 institutions and more
than 14,000 investigators./A7
Ebb & Flow
Strategy
Erecting its Pillars — Message in Vertex
jump on VX-770. Clinical Data fantasies. 4SC
goes outside the family. IPOs: Dermagraft
redux. Also: Delcath; Ligand; Salix; ProStrakan;
Quest; Transgene, et al./A15
Cancer Encore — Gilead’s first move into
cancer ended when it sold off its liposomal
chemotherapeutics. This time the biotech is
collecting targeted therapies with potential in
cancer and inflammation, possibly in combination./A9
Virtue in Virtual — Atlas Venture is starting
to invest in assets instead of companies, aiming
to pluck assets from pharma and reduce
capital intensity by outsourcing and having
virtually no dedicated management./A13
Online this week/A19
Stock charts & tables/A21
Company index/A10
BioCentury 100 Indicators
TM
Two for One — By binding GD2 and releasing
IL-2 at the tumor site, Apeiron believes APN301
will be able to deliver a one-two punch in
neuroblastoma while avoiding the toxicities of
systemic IL-2./A11
Week ended 02/25/11
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By Susan Schaeffer
Senior Editor
A study reported this month in the
Journal of the American Medical Association
challenges the standard practice of removing cancerous lymph nodes from the
underarms of women with breast cancer.
For patients, its finding represents the best
of what the NCI’s Clinical Trials Cooperative Groups can be.
The flip side is the snail’s pace at which
the cooperative system works, which means
many trials never finish, or are irrelevant
by the time they do.
There is broad agreement the cooperative groups must start studies faster,
and and NCI already has implemented
changes designed to do just that.
But that is about where the consensus
ends.
Illustrating the best of the cooperative
system, the Z0011 trial published this
month by the American College of Surgeons Oncology Group (ACOSOG)
showed sentinel lymph node dissection
(SLND) is noninferior to complete axillary
lymph node dissection (ALND) on survival in women with some types of breast
cancer.
The study thus could spare thousands
of women each year from the complications of ALND, including infection and
lymphedema, improving quality of life without shortening its length.
See next page
This Week in SciBX
Geography Lesson in Dry AMD — American researchers have identified a
mechanism in the retina that could be responsible for triggering the blindness
associated with advanced dry AMD. Please see Table of Contents on A10.
BioCentury TV This Week
Are Biotech’s Pioneers Disappearing?
Please see the Program Notes on A8.
www.biocenturytv.com
Future Leaders Update
Expanding the slate for both financial and strategic dealmakers. Please see announcement following A20.
BioCentury,
THE
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Product Discovery & Development,
from previous page
For more than 50 years, the cooperative groups have helped define the practice of oncology. Their landmark studies
have directed physicians to the most effective drug combinations, spared patients
unnecessary invasive surgeries, optimized the use of radiation and other
interventions and improved prevention
and diagnosis (see “Understanding the
Co-ops,” A7).
Yet last April, the Institute of Medicine said the cooperative group program
is “approaching a state of crisis.” According to the report, which was commissioned by NCI, inefficiencies and lack of
funding threaten the program’s continued
ability to conduct the kinds of large-scale,
innovative trials needed to advance patient care.
As a result of a complex system of
oversight, the median time required to
design, approve and activate a Phase III
trial is 2.5 years. Because of these delays,
a large proportion of studies go unfinished, often because the questions they
were designed to answer became irrelevant.
Only 60% of trials begun by cooperative groups are completed and published.
Furthermore, between fiscal 2002 and
FY08, funding for the program decreased
by 20% after adjusting for inflation. Meanwhile, knowledge of the molecular changes
underpinning cancer and the use of predictive biomarkers are increasing the complexity and cost of cancer studies.
IOM and NCI say consolidating the
cooperative groups’ operations and requiring them to compete for funding will
make the program more efficient, while
ensuring continued competition for the
best ideas. IOM recommended, and NCI
has agreed, that the nine existing cooperative groups focused on adult cancers must
be reduced in number.
But some clinical researchers, industry
stakeholders and members of the cooperative groups themselves say it’s not
obvious how these efficiencies will be
achieved, and they are concerned that
having fewer cooperatives will result in
fewer innovative ideas being tested.
The debate will take years to play out,
as NCI expects to issue a funding opportunity announcement (FOA) around July
2012, beginning a competition from which
four adult groups and one pediatric group
will emerge victorious after October 2013.
A window into the process will open
on March 21, when the cooperative group
See the Doroshow Interview
“I think in the future we
will have to have a system
beyond what most pharmas
can do, that can screen
thousands of patients,
that has 2,000 sites up,
ready and ongoing, that
will allow us to find the
next ALK inhibitor.”
James Doroshow, NCI
chairs, NCI leadership and stakeholders
from industry, payers and patient groups
meet for a public workshop at the IOM in
Washington.
Time to progression
No one is arguing the cooperative
groups don’t desperately need to reduce
the amount of time it takes to start trials.
Last April, James Doroshow, director of
NCI’s Division of Cancer Treatment and
Diagnosis, implemented new deadlines and
processes aimed at speeding the timelines.
According to a study team led by
David Dilts and including Doroshow, opening a Phase III cooperative group study
requires 769 steps and 36 approvals and
takes a median of 2.5 years.
Dilts is director of clinical research at
Oregon Health & Science University’s
Knight Cancer Institute and professor of
healthcare management in the university’s
Division of Management. He was also a
member of the IOM committee that drafted
the April report.
The lengthy delays are not due to any
one part of the approval process, but
rather because review of a protocol by
one body, such as NCI or an institutional
IRB, can trigger feedback loops as a protocol is passed back and forth between the
investigators, the cooperative group, NCI,
IRBs and FDA, sometimes for the sake of
FEBRUARY 28, 2011
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relatively minor changes.
Most of these reviews are done in
sequence rather than in parallel, and most
of the review questions and comments are
transmitted in writing.
The study, published in Clinical Cancer
Research in November, went on to show
that the longer it takes to launch a trial,
the less likely the study is to reach patient
accrual targets.
“For studies that took more than two
or three years to even open, their success
rate of completion, because the science
had changed, was very low,” Doroshow
said on the Feb. 20 edition of BioCentury
This Week, BioCentury’s public affairs
television program.
Every incomplete study extends false
hope to patients who expect their participation in clinical trials will contribute to
better treatments.
Delays also have discouraged some
industry sponsors from placing important
trials at the cooperative groups. This means
the companies have less access to the
cooperative group’s infrastructure and
expertise, and that the cooperative groups
have less access to novel compounds —
and to supplemental funding from industry.
“Study startup time, which has been
extremely long, has played a role in determining whether a sponsor would place an
important study with cooperative groups,”
said Peter Ho, co-founder and president of
cancer company BeiGene Ltd. “For industry, we’d like to get going in Phase II in
4-6 months.”
Ho was previously VP of oncology development at Johnson & Johnson, SVP of the
Oncology Center of Excellence in Drug
Discovery (CEDD) at GlaxoSmithKline
plc and, in the 1990s, worked as part of
NCI’s Cancer Therapy Evaluation Program (CTEP), a group within the Division
of Cancer Treatment and Diagnosis that
oversees the cooperative groups.
Sean Harper, SVP of global development and CMO at Amgen Inc., agreed
timelines influence decisions to place studies with cooperative groups. “Major factors for deciding are timelines, which can
be very long,” he told BioCentury.
Amgen does many studies with NCI
and its cooperative groups, Harper said,
but generally not studies intended for
registration unless they are measuring
hard endpoints.
“Generally, either we use them as ways
to screen different tumor types, which we
would follow up with Amgen-sponsored
studies, or if measuring survival,” he said.
See next page
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IOMs recommendations for NCI
In an April 2010 report commissioned by the National Cancer Institute and the Institute of Medicine said the structure and processes of the entire
cancer clinical trials system needs to be redesigned to reduce redundancy and improve the effectiveness and efficiency of the studies. Based on input
from oncology experts and the literature, IOM concluded fixing the system will require participation from academia, government, industry and the public.
Its recommendations are summarized below.
Goal
Supporting recommendations
Improve speed and efficiency
NCI should facilitate some consolidation of cooperative group front office operations (scientific
committees and statistical offices) by reviewing and ranking the groups and by linking funding to review
scores
NCI should require consolidation of administration and data management operations of the cooperative
groups, and make process improvement in the operational and organizational management of clinical trials a
priority
HHS should lead a transagency effort to streamline and harmonize government oversight and regulation of
cancer clinical trials
Incorporate innovative science
and trial designs
NCI should mandate submission of annotated biospecimens from cooperative group trials to high-quality,
standardized central biorepositories, and should fund management and use of those resources for
retrospective correlative science
Cooperative groups should lead the development and assessment of innovative designs for clinical trials that
evaluate cancer therapeutics and biomarkers
NCI, in cooperation with other agencies, should establish a consistent, dynamic process to oversee the
development of national unified standards for oncology research
Improve prioritization and
completion of trials
NCI should reevaluate its role in the clinical trials system, including filing more INDs for high-priority trials
and strengthening peer review of trial concepts
NCI, cooperative groups and physicians should take steps to increase the speed, volume, and diversity of
patient accrual and to ensure high-quality performance at all trial sites
Increase funding for cooperative groups and, if necessary, reduce the number of trials to ensure funding for
those of highest priority
Incentivize participation of
patients and physicians
Academic medical centers, community practices, professional societies and NCI should work to ensure that
clinical investigators have adequate training and mentoring, paid protected research time, resources and
recognition for participating
Government and private payers should compensate for care provided to patients in clinical trials
from previous page
“Things that absolutely have to work,
we do ourselves. Things that are more
flexible, or for large studies where you
would compete with cooperative groups
— or big adjuvant studies, for example,
that take seven years to do — make you
lean toward cooperative groups,” he
added.
Ho agreed cooperative groups are ideal
for some kinds of trials, such as studies in
rare tumors. “It takes a lot for a sponsor to
put together a group of investigators and
sites. In the cooperative group, that mechanism, that organization, might be set up
already,” he told BioCentury.
David Parkinson, who has led several
oncology R&D groups and also worked
within CTEP, concurred “there are certain types of trials only cooperative groups
can do.”
As an example he cited adjuvant trials,
“which have been very, very large historically and long because of the endpoints,
and essentially have not been and prob-
ably should not be done by industry.”
Parkinson is now president and CEO
of diagnostic company Nodality Inc.,
and previously was SVP of oncology R&D
at Biogen Idec Inc., VP and head of
oncology development at Amgen, head of
oncology at Novartis AG, chief of NCI’s
Investigational Drug Branch and acting
associate director of CTEP.
While he said the cooperative groups
“involve the leading oncologists of any
era,” Parkinson said he would not likely
entrust a key trial to them — “not if the
trial were integral to the survival of my
company.”
Thus, he told BioCentury, “I would not
put my main registrational trial in a cooperative group. I would consider secondary
indication trials, or trials helping to answer biological questions about which
subgroups of patients are appropriate.”
Response rates
Under Doroshow’s initiatives, the
groups have already reduced the time to
activate and open studies by 60%.
Some of the solutions have been surprisingly simple. One of the biggest
changes, he told BioCentury, was to insist
on deadlines for every step of the process.
He also instituted the use of conference
calls for investigators to respond to IRB
questions about protocols in real time
instead of engaging in back-and-forth
email.
“That saves literally months and costs
nothing. In fact it saves money,” Doroshow
said.
NCI also provided grant supplements
so the groups could hire staff to ensure
deadlines are met.
The deadlines and process changes
went into effect April 1, 2010. Jan. 1 was
the first “drop-dead” date, the point at
which any trial was to be dropped if the
cooperative groups had been working on
it for two years but the study had not yet
been started.
“Only three trials out of hundreds that
could have been terminated were,”
Doroshow said.
The goal is to be consistent with indusSee next page
BioCentury,
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try norms. “Another six months from
now, I’ll know just how well we’re hitting
these early timelines,” Doroshow said.
“It’s been quite a year, and turn-around
time to approval has gone from 120-140
days to 40 days.”
The next part of Doroshow’s plan is
the installation of a clinical trials data
management system that will be used by
all the cooperative groups.
The system will allow Internet-based
patient enrollment and randomization,
replacing a paper-based process that is
both tedious and error prone. It also will
function as a uniform collection system for
clinical data from all sites involved in a
trial, with standardized case report forms.
“One of the most important things is to
make it easy for both patients and for
participating physicians to participate,”
Doroshow said on BioCentury This Week.
“We hope soon to be able to put forward
a national system for clinical trials data
management, an IT system that will be
uniform across the country that will allow
investigators — whether they are in a
private office or at an academic medical
center, no matter what the study is and
who originated the study — to have a
standard approach to electronic data entry.”
Susan Desmond-Hellmann, chancellor
of the University of California, San
Francisco and former president of product development at Genentech Inc.,
said a uniform IT system could improve
both efficiency and data quality, which is
sometimes a bigger issue in cooperative
group trials than in industry trials.
Standardizing the data “is a huge advance,” she told BioCentury.
Antiproliferative effect
IOM says reducing study timelines and
implementing a unified data management
system alone will not be sufficient to improve efficiency and enable the groups to
incorporate more innovative science into
their studies. That, the report said, will
require consolidating the cooperatives into
a smaller number of groups, as well as
increasing their funding (see “IOM’s Recommendations to NCI,” A3).
According to the report, a smaller
number of groups ideally would maintain
strong competition for trial concepts and
help ensure that only the highest-priority
trials are undertaken.
Indeed, according to IOM, there is no
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“Things that absolutely
have to work, we do
ourselves.”
Sean Harper, Amgen
system for prioritizing the most important
studies, or those most likely to succeed.
NCI has 10 disease-specific scientific
steering committees charged with prioritizing and refining concepts for Phase II
and III trials to better allocate resources,
increase scientific quality and reduce duplication.
There are steering committees for gastrointestinal, gynecologic, head and neck,
genitourinary, breast, thoracic and brain
cancers, plus leukemia, lymphoma and
myeloma. Each one is composed of outside cancer experts and NCI senior investigators.
However, the committees do not rank
trial concepts against each other.
While IOM neither specified the ideal
number of groups, nor indicated which
should merge or remain independent, the
report did note: “Groups focused on a
single disease site or modality would likely
need to merge with multidisciplinary
Groups under this system.”
In a presentation to the group chairs in
November, Doroshow said NCI had determined four adult groups and one pediatric group are the right numbers. The
ability to “prioritize molecular characterization resources and develop molecularly
driven trial designs” can “be achieved
more easily with fewer competing research
organizations,” according to slides from
Doroshow’s presentation.
The presentation also said the planned
IT system for clinical data management
and tissue resource management “will
constantly require modification,” which
would be “more manageable with fewer
independent entities.”
The presentation did not say which
groups might be the surviving entities, but
did suggest “scientific interactions around
imaging” would be facilitated by integrating the American College of Radiol-
“I would not put my
main registrational trial in
a cooperative group.”
David Parkinson, Nodality Inc.
FEBRUARY 28, 2011
P AGE A4 OF 20
ogy Imaging Network (ACRIN) into a
“setting with more access to patient resources for investigational studies.”
Minetta Liu, associate professor of
medicine and oncology in the Lombardi
Cancer Center at Georgetown University, is a proponent of consolidation.
“What will be key is how the groups
realign. Not every group is structured in
the same way, and their talents are different. Combining groups with different
strengths may foster better ideas,” she
suggested.
“If you took a surgical group — hypothetically speaking — and merged it with
one of the larger oncology groups, we
could increase the number of meaningful
collaborations between medical oncology,
surgery and radiation medicine,” Liu told
BioCentury.
Liu is the principal investigator for
Cancer and Leukemia Group B
(CALGB) at Georgetown and a member of
CALGB’s breast cancer committee, correlative science subcommittee, executive
committee and data audit committee. She
also was a member of the IOM committee
that drafted the April report.
Doroshow argued that revamping the
system to function as a truly national
network is essential to bolstering the cooperatives’ ability to incorporate modern
tools of molecular oncology.
“I think in the future we will have to
have a system beyond what most pharmas
can do, that can screen thousands of
patients, that has 2,000 sites up, ready
and ongoing, that will allow us to find the
next ALK inhibitor,” he told BioCentury.
About 3-5% of non-small cell lung
cancer (NSCLC) tumors are anaplastic
lymphoma kinase (ALK)-positive.
“If we are going to cure lung cancer 3%
at a time, we need access to sites, science
and systems that can find patients and
pilot these ideas, and to work with pharma
to do it,” Doroshow said.
Nodality’s Parkinson agreed. “Industry is giving lip service to biomarkers,
usually against conventional indications,
because they believe that’s what regulators want to see,” he said. “But there’s no
better way to identify subsets than cooperative group trials, because they have all
the basic science, pharmacology and clinical investigators.”
The problem, Parkinson said, is “the
groups are slow and ponderous and don’t
have the resources to do the biological
characterization that’s necessary for more
appropriate and efficient characterization
of patients.”
See next page
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William Hait, global therapeutic area
head for oncology R&D at J&J, also cautioned that the cooperative groups will
need more than streamlined operations
and additional funding to perform
biomarker research with the rigor that
would be required to support registration.
“It’s a huge education issue at the site
level, how specimens are harvested, annotated, etc. The cooperative groups are
good at rounding up paraffin-embedded
specimens. But for many tests you need
not only paraffin-embedded biopsies, but
biopsy samples that are frozen and handled
in different ways,” he told BioCentury.
Developing resistance
NCI has made it plain it does not
intend to foist a specific consolidation
plan onto the cooperative groups, preferring instead to let the group chairs work it
out. But while the chairs’ initial response
to IOM recommendations was favorable,
resistance has since bubbled up.
In a public comment on the IOM report
issued last September by the Coalition of
Cancer Cooperative Groups, nine of the
group chairs said they have begun to take
steps to improve operational efficiency.
They cited adherence to the new timelines
and the planned adoption of a common
data management system as examples.
Three of the groups, ACOSOG, North
Central Cancer Treatment Group
(NCCTG) and CALGB, were already discussing consolidating their biostatistical
and data management centers before the
IOM report came out, and that consolidation is now well under way.
The chairs added: “An internal dialogue is underway to address the optimal
configuration of our scientific programs
and portfolios, building on our diversity
and strengths.”
The comment was signed by all the
group chairs except Laurence Baker of
SWOG. Baker declined to be interviewed
for this story, but group spokesperson
Frank DeSanto confirmed SWOG is not
currently discussing a merger with any of
the other cooperative groups.
And in January, Gynecologic Oncology Group chair Philip DiSaia issued
a white paper arguing GOG should not be
merged with any other groups.
His argument was predicated on GOG’s
unique focus, its accomplishments in clinical and translational research, and differences in the practice of gynecologic oncol-
ON
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“Should the spirit and
integrity of the GOG be
disrupted by attaching
portions to various large
medical oncology groups,
the outcome will be
repeated failure.”
Philip DiSaia,
Gynecologic Oncology Group
ogy compared with other cancer disciplines.
“The study of gynecologic cancers has
been attempted by Groups other than the
GOG. In point of fact, SWOG has attempted to accomplish this on two occasions without success, and ECOG’s attempt in this area also was unsuccessful,”
the white paper noted.
DiSaia warned: “Should the spirit and
integrity of the GOG be disrupted by
attaching portions to various large medical oncology groups, the outcome will be
repeated failure.”
The Eastern Cooperative Oncology Group (ECOG) and SWOG are the
two largest cooperative groups.
DiSaia told BioCentury he fears merging into a larger group will limit the number of gynecological studies that get approved. “SWOG, for instance, has a quota
on how many protocols the myeloma
committee can develop and how many
leukemia can develop. We believe we
would be compromised on the number of
ideas we could pursue,” he said. “Now, we
go for the important ideas, and when we
don’t have the money, we go get it from
industry.”
Moreover, according to DiSaia, “none
of the big groups want us, and NCI doesn’t
want us to join them anyway. That leaves
the radiation oncology group, NSABP,
ACRIN — it’s like oranges, apples, kum-
“One hopes the number of
ideas and studies goes up
by decreasing the number
of groups, but it’s not
immediately clear how
that will happen.”
John Erban, Tufts Medical Center
FEBRUARY 28, 2011
P AGE A5 OF 20
quats and plums. At least when you merge
banks, they’re both banks,” he said.
DiSaia said he has reached out to the
Radiation Therapy Oncology Group
(RTOG) and the National Surgical
Adjuvant Breast and Bowel Project
(NSABP), to no avail.
“Radiation and NSABP are already
talking about a merger. I have approached
the chairs and said we’d be the third, but
they want to work out their own marriage
before they open the marriage,” he said.
DiSaia added his group is considering
competing for one of the four new cooperative group awards NCI plans to issue in
FY14.
“If we are not chosen, [NCI] will have
to face the political pressure of not studying female gynecological cancers,” he told
BioCentury.
DiSaia also is not moved by the IOM
and NCI arguments that consolidating
and streamlining the groups will better
enable them to engage in the translational
work necessitated by the advent of targeted therapies.
“All the groups have a plethora of
really good science going on that’s not
part of a protocol. You don’t want to
tamper with that,” he said.
DiSaia is not alone in his concerns that
consolidation could result in fewer ideas
reaching the clinic.
“One hopes the number of ideas and
studies goes up by decreasing the number
of groups, but it’s not immediately clear
how that will happen,” said John Erban,
associate director for clinical science and
clinical director of Tufts Medical Center Cancer Center.
The IOM report suggested the merger
that formed the Children’s Oncology
Group (COG) should serve as a template
for the adult groups.
But Erban argued the pediatric groups
had little choice but to merge because of
the scarcity of pediatric patients.
“They have 1,000 patients per year or
2,000 patients per year with particular
diseases and there simply can’t be four
cooperative groups enrolling different trials. One breast cancer trial might require
3,000-5,000 patients, but many, many
more patients are eligible for those trials,”
he said.
Maha Hussain, professor and associate
director for clinical research at the University of Michigan Comprehensive
Cancer Center, also has doubts that
consolidation will result in more and better ideas. Hussain is co-chair of SWOG’s
prostate cancer committee, but said she
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was not speaking on behalf of SWOG.
“The IOM report is legit, and they
brought up very good points. But as an
investigator I am somewhat skeptical that
the changes will actually improve the process,” Hussain said.
Consolidation “may help in that you
are bringing more brains together. But
unless you bring the resources and infrastructure, I don’t see it. We participate in
cooperative groups as volunteers; we don’t
get paid to participate. And volunteers
need resources to accomplish big ideas,”
she said.
Growth factors
But one of IOM’s recommendations —
that funding for the groups be increased
— is unlikely to happen any time soon.
During a town hall meeting for NCI webcast
on Jan. 10, institute Director Harold
Varmus said he did not expect any budget
increase for NIH, and that threats from
Republican leadership in the House to roll
back funding to FY08 levels are “certainly
real for 2012.”
Nevertheless, Varmus named fixing the
cooperative groups as a priority, and said
in the absence of new funding, NCI would
have to find the money elsewhere in its
“commitment base,” the portion of the
budget earmarked for things like salaries
and noncompeting grants.
The details of how the groups will be
ON
B IOB USINESS
FEBRUARY 28, 2011
“We participate in
cooperative groups as
volunteers; we don’t get
paid to participate.
And volunteers need
resources to accomplish
big ideas.”
Maha Hussain,
University of Michigan
funded have not been released. According
to its timeline, NCI will develop and issue
new guidelines for a national clinical trials
network, plus the funding opportunity
announcement, around July 2012.
Applications from groups will be reviewed during 2013, with new awards to
be issued in FY14.
The four surviving adult groups and
COG will undergo competitive review
every five years. All five groups will be
reviewed in the same year “so that the
“The numbers tell the story:
more and more
registration trials are
conducted outside the U.S.”
William Hait, J&J
COMPANIES AND INSTITUTIONS MENTIONED
American College of Radiology Imaging Network (ACRIN), Philadelphia, Pa.
American College of Surgeons Oncology Group (ACOSOG),
Durham, N.C.
Amgen Inc. (NASDAQ:AMGN), Thousand Oaks, Calif.
BeiGene Ltd., Beijing, China
Biogen Idec Inc. (NASDAQ:BIIB), Weston, Mass.
Cancer and Leukemia Group B (CALGB), Chicago, Ill.
Children’s Oncology Group (COG), Arcadia, Calif.
Eastern Cooperative Oncology Group (ECOG), Philadelphia. Pa.
Genentech Inc., South San Francisco, Calif.
Georgetown University, Washington, D.C.
GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K.
Gynecologic Oncology Group (GOG), Philadelphia, Pa.
Institute of Medicine (IOM), Washington, D.C.
P AGE A6 OF 20
Groups can be directly compared and
resources allocated appropriately, based
on the outcome,” according to slides from
Doroshow’s presentation.
Going forward, Doroshow told
BioCentury, the groups will be funded
based on not only their ability to develop
trials, but also whether they work well
with other groups to bring forth novel
ideas and accrue patients to studies that
originate at other groups.
Even if the stakeholders differ on how
to accomplish the restructuring, they agree
it must be done to preserve patient access
to clinical trials and effective therapies.
“Increasingly, if the cooperative group
mechanism does not work, for big, important trials, people will go ex-U.S. That will
decrease access to trials for U.S. patients
and will mean studies are not representative of the U.S. population for approval,”
Desmond-Hellmann said.
Parkinson and Hait both said that’s
already happening.
“The numbers tell the story: more and
more registration trials are conducted
outside the U.S. Clinical research gives
patients early access to the best drugs,
and having these trials exported reduces
access for U.S. patients,” Hait told
BioCentury.
Parkinson added: “If it takes too long,
the groups will lose their relevance. I have
a sense of urgency about this. I think
there’s no excuse. We have the technology. People have been talking about this
for 15 years, and it hasn’t made it better;
it has gotten worse.”
Johnson & Johnson (NYSE:JNJ), New Brunswick, N.J.
National Cancer Institute (NCI), Bethesda, Md.
National Surgical Adjuvant Breast and Bowel Project (NSABP),
Pittsburgh, Pa.
Nodality Inc., South San Francisco, Calif.
North Central Cancer Treatment Group (NCCTG), Rochester,
Minn.
Novartis AG (NYSE:NVS; SIX:NOVN), Basel, Switzerland
Oregon Health & Science University, Portland, Ore.
Radiation Therapy Oncology Group (RTOG), Philadelphia, Pa.
SWOG, Ann Arbor, Mich.
Tufts Medical Center Cancer Center, Boston, Mass.
University of California, San Francisco (UCSF), San Francisco, Calif.
University of Michigan Comprehensive Cancer Center, Ann Arbor,
Mich.
All press releases, news announcements and story inquiries should be submitted to our
news room at pressreleases@biocentury.com. Editorial announcements emailed to the Editor-in-Chief
and/or the Publisher may not receive immediate attention and potential stories will be delayed.
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A7 OF 20
Curing Cancer Trials
Understanding the co-ops
By Susan Schaeffer
groups, the cure rate of childhood cancers has climbed from
Senior Editor
about 10% in the 1950s to nearly 80% today.
Since its inception in the 1950s, the cooperative oncology
Indeed, 90-95% of all children with a newly diagnosed cancer
group system has been instrumental in establishing standards for are seen at an institution that participates in COG. If they qualify
cancer treatment and clinical research.
for a clinical trial, more than half of these children participate; for
NCI’s Clinical Trials Cooperative Group Program is the children less than five years of age, the rate is closer to 90%.
nation’s largest publicly funded clinical trials network, consisting
of nine groups focused on adult cancers, and one focused on
Under scrutiny
pediatric cancers.
There are four main types of groups: some focus on particular
But despite their track record of accomplishment, the coopdiseases, such as the Gynecologic Oncology Group (GOG); erative groups have been under scrutiny almost since day one.
some focus on a particular treatment modality, such as the Indeed, many of the concerns highlighted in an Institute of
Radiation Therapy Oncology Group (RTOG); some focus Medicine report last April were raised in August 1997 in a
on a particular patient population, such as the Children’s report by NCI’s Clinical Trials Program Review Group, now
Oncology Group (COG); and a few are large multimodality known as the “Armitage Report.”
groups such as SWOG.
Armitage concluded the clinical trials
Cooperative groups provide funding,
system had become bogged down by com“This complexity has bred
oversight and data management for trials
plexity arising from collaboration between
conducted by a network of members inmultiple parties including investigators,
inefficiencies and eroded
cluding researchers, cancer centers, and
physicians, industry, academia and NCI.
the ability of the system to
community physicians throughout the U.S.,
“This complexity has bred inefficiencies
Canada and Europe. Each group has an
and eroded the ability of the system to
generate new ideas to
operations center and a statistical center,
generate new ideas to reduce the cancer
reduce the cancer burden.”
scientific committees and data manageburden,” the report said.
ment infrastructure.
At the same time, Armitage noted that
The “Armitage Report”
In total, the program involves more
funding was becoming scarce, even as the
than 3,100 institutions and more than
availability of new therapeutics and tech14,000 individual investigators. The cooperative groups place nologies that needed to be tested was accelerating.
more than 25,000 patients into clinical trials — mostly multicenter
According to David Parkinson, who was acting associate
Phase II or III studies — each year.
director of NCI’s Cancer Therapy Evaluation Program (CTEP) at
Historically, these have been large trials to answer questions the time, the system failed to keep pace with new developments
that are important to oncologists and cancer patients, but are in clinical science and with industry’s growing ability to develop
unlikely to be undertaken by industry, such as effective combi- cancer drugs. CTEP, a group within NCI’s Division of Cancer
nations of approved drugs, or comparisons between different Treatment and Diagnosis, oversees the cooperative groups.
drugs or interventions.
Parkinson is now president and CEO of diagnostic company
A prime example is a study published this month in the Journal Nodality Inc.
of the American Medical Association by the American College of
Little has changed since the Armitage Report was published.
Surgeons Oncology Group (ACOSOG). It compared axillary The review process remains cumbersome and the groups are still
lymph node dissection and sentinel lymph node dissection.
underfunded.
Axillary lymph node dissection (ALND) involves removing
In 2010, the cooperative groups had a budget of just $238
the axillary lymph nodes as a means of staging breast cancer and million. NCI also provides per-patient reimbursement for group
achieving local disease control. The method risks complications trials, but the amount has been set at $2,000 per patient since
such as seroma, infection, and lymphedema, and mounting 1999. In June 2008, NCI began using a rating system to increase
evidence has suggested the procedure produces no benefit on reimbursement for “complex” trials, but the maximum persurvival or disease activity.
patient reimbursement is still just $3,000.
Sentinel lymph node dissection (SLND) was developed as a
According to IOM, in 2004 median per-patient costs for
way to stage cancer with less risk. SLND involves injecting the cancer trials were $3,500 for Phase III trials and $6,000 for Phase
tumor with dye, and then selectively removing only the lymph II trials.
nodes that take up the dye.
As a result, up to half the costs of cooperative group trials are
When the tumor-draining lymph nodes are free of cancer, no borne by the investigators and other care providers who do the
further surgery is performed. However, when the sentinel lymph studies, which IOM noted creates a large disincentive for
nodes (SLNs) are cancerous, subsequent ALND has remained physicians to participate.
standard of care. The ACOSOG study found that SLND alone
“It is not surprising that physician preferences are to treat
was noninferior to ALND on survival and disease-free survival. patients with the standard of care or with a therapeutic agent off
Perhaps the best example of the ways cooperative groups can protocol, rather than being involved in a significantly more costly
change cancer treatment comes from the Children’s Oncology and more burdensome clinical trial,” the report said.
Group. Thanks in large measure to trials conducted by pediatric
See next page
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A8 OF 20
Curing Cancer Trials,
from previous page
BioCentury
THE BERNSTEIN REPORT ON BIOBUSINESS
Editorial & Research
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One consequence of such physician disincentives is low levels of patient participation
in trials. Only 2-3% of adults with cancer participate in clinical trials (see Cover Story).
American College of Surgeons Oncology Group (ACOSOG), Durham, N.C.
Children’s Oncology Group (COG), Arcadia, Calif.
Gynecologic Oncology Group (GOG), Philadelphia, Pa.
Institute of Medicine (IOM), Washington, D.C.
Nodality Inc., South San Francisco, Calif.
Radiation Therapy Oncology Group (RTOG), Philadelphia, Pa.
SWOG, Ann Arbor, Mich.
www.biocentury.com
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See next page
Read the Story, Watch the Show
Read BioCenturys Feb. 21 Cover Story on the
Genzyme-sanofi deal and the future of big biotech
View the entire public affairs TV program now at
www.biocenturytv.com
With the news that French giant sanofi-aventis will acquire Genzyme for
more than $20 billion, BioCentury This Week on Feb. 27 featured an
exclusive interview with former MedImmune CEO David Mott on whether
this second-largest ever takeout of a biotech company is a sign that
biotech pioneers are disappearing, and what the future looks like for the
next generation of big thinking innovators.
Near Death
Former MedImmune CEO David Mott recounts how the company overcame
four years of financial and scientific near death setbacks to create breakthrough
drugs and ultimately be acquired by AstraZeneca.
Headwinds
While Mott sees an abundance of opportunities for new companies, he also
says Americas ability to replenish innovation is slowing down while product
development is moving outside the U.S.
What to Fix
After the Genzyme takeout, Mott cites worries about VCs and CEOs who
think smaller, the urgency to take politics and media out of FDA decisions, and
the need for a new biobanking infrastructure.
The Final Word
BioCenturys Steve Usdin says Washington must learn from the stories of
the biotech pioneers.
Web Exclusive: Investing Now
Now a VC at NEA, Mott says next-generation biologics and new scaffolds
for making better antibodies are set to lead innovation, but has questions about
vaccines, diagnostics.
Charter Sponsorship from BIO, Biogen Idec, and Rodman & Renshaw
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A9 OF 20
Strategy
Gilead’s cancer encore
By Michael Flanagan
should emerge that will be developed for cancer.
Senior Writer
The company also had cgi1842, an angiogenesis inhibitor
Gilead Sciences Inc.’s initial dalliance with cancer ended targeting EPH receptor B2 (EPHB2) and VEGF receptor 2 (KDR/
in 2001 when it sold its portfolio of liposomal chemotherapeu- Flk-1; VEGFR-2) in Phase I testing for cancer. However, this
tics. A decade later, the company is jumping back in, this time by program was out-licensed to Jubilant Innovations Ltd.
acquiring companies with targeted therapies against novel tarFrom Arresto, Gilead gained access to allosteric inhibitors of
gets.
enzymes found in the extracellular matrix, which have potential
Gilead is not detailing its strategy, but all three deals involve for both cancer and fibrotic disorders (see BioCentury, June 28,
programs that address both inflammation and oncology, and 2010).
appear to include compounds that could be paired in combinaArresto’s lead product, AB0024, is a mAb against lysyl
tion regimens.
oxidase-like 2 (LOXL2). The enzyme cross-links collagen, creatGilead’s third transaction in eight months was announced ing a scaffold for fibroblasts to grow on, and is involved in the
last week: a $375 million deal for Calistoga Pharmaceuticals production of growth factors, such as VEGF, connective tissue
Inc., which has a small molecule phosphoinositide 3-kinase growth factor (CTGF), and transforming growth factor (TGF)
(PI3K) delta inhibitor, CAL-101, in Phase II testing for indolent beta.
non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukeAB0024 is in Phase I testing for advanced solid tumors and
mia (CLL).
idiopathic pulmonary fibrosis (IPF).
Gilead acquired Arresto BioSciences
Gilead has suggested Arresto’s antiInc. for $225 million in December, and
fibrosis
programs will fit its efforts to build
“I think they are building a
paid an undisclosed amount for CGI Pharfranchises in liver, pulmonary and cardiopipeline of key mechanisms
maceuticals Inc. last June.
vascular diseases (see BioCentury, Jan. 3).
Gilead’s first foray into cancer drug
The most advanced of the acquired
that could some day be
development was its 1999 acquisition of
programs is Calistoga’s CAL-101. Its tarNeXstar Pharmaceuticals Inc. for $550
get, PI3K delta, is a protein involved with
combinable.”
million in stock.
cell proliferation, survival and trafficking.
At the time, Gilead said the primary
Calistoga has focused on a set of selective
Carol Gallagher, Calistoga
driver was its desire to move into the
inhibitors licensed from Icos Corp. (now
cancer space, where the regulatory envipart of Eli Lilly and Co.).
ronment allowed for rapid drug development (see BioCentury
“The dogma for PI3K in cancer has always been to focus on
Extra, March 2, 1999).
the alpha isoform because it has a number of point mutations
The cancer programs were mostly liposomal formulations of known to be associated with solid tumors,” Calistoga President
chemotherapeutics. They included DaunoXome liposomal and CEO Carol Gallagher told BioCentury.
daunorubicin, which was marketed for AIDS/HIV-related Kaposi’s
However, she noted, PI3K alpha “is ubiquitous in all cells,
sarcoma; NX211, a liposomal camptothecin analog that moved where it controls glucose regulation and insulin signaling located
into Phase II testing for solid tumors; and GS7904L, a preclinical in almost every cell in the body.” Interrupting this can cause
liposomal thymidylate synthase inhibitor. There was also a safety problems.
nucleoside analog, GS7836, in Phase I testing for solid tumors.
“Our founders observed that PI3K delta plays an important
Two years later, Gilead decided to aim for profitability by role in B cell signaling,” which provided the rationale for
focusing on its marketed antiviral portfolio. Most of the cancer evaluating CAL-101 in the B cell malignancies NHL and CLL,
assets were sold to OSI Pharmaceuticals Inc. (now part of Gallagher said. “I believe that we’ve got a three- to four-year
Astellas Pharma Inc.) in 2001. DaunoXome was licensed to head start on the competition as far as PI3K delta inhibitors go.”
Diatos S.A. in 2006.
In separate Phase I trials, NHL patients given CAL-101
Gilead is taking a different approach this time, most notably monotherapy had a 63% response rate, while 80% of CLL patients
by focusing on targeted agents addressing novel pathways.
receiving CAL-101 plus Rituxan rituximab had more than a 50%
Spokesperson Nathan Kaiser told BioCentury the company’s decrease in tumor volume in the lymph nodes.
strategy has evolved in parallel with the field of cancer research.
Calistoga had planned to start Phase III trials of CAL-101 this
“Over the last decade or so, there has been a dramatic increase year as monotherapy for indolent NHL and in combination with
in the understanding of the genetic basis of cancer, which has Rituxan for CLL, but Gallagher said the timing is now up to
allowed for the development of disease-specific targeted thera- Gilead. “We had hoped to be ready to begin commercializing the
pies,” he said.
product in the U.S. by the end of 2013,” she added.
Another difference, Kaiser noted, is that Gilead is particularly
Calistoga also had planned to start Phase I testing this year
interested in finding assets with broad potential in both cancer of two more selective PI3K inhibitors: CAL-129, a PI3K delta
and inflammatory conditions.
inhibitor for inflammatory/autoimmune diseases, and CAL-120,
CGI provided Gilead with a library of Syk tyrosine kinase a dual beta and delta inhibitor for cancer.
(SYK) inhibitors that Kaiser said have shown potential in
Rituxan is marketed by Biogen Idec Inc. and Roche’s
inflammatory diseases and cancer. CGI’s preclinical program is Genentech Inc. unit.
for rheumatoid arthritis (RA), he said, but other molecules
See next page
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A10 OF 20
Strategy,
from previous page
SciBX This Week
ANALYSIS
COVER STORY
Geography lesson in dry AMD
American researchers have identified a mechanism in the
retina that could be responsible for triggering the blindness
associated with advanced dry age-related macular
degeneration, which currently is untreatable. The team will
develop inhibitors for preclinical testing and hopes eventually to submit an IND to FDA.
TARGETS & MECHANISMS
Seeing the light in melanoma
U.S. researchers have shown that UV light induces the
expression of interferon-γ, which may drive the formation
and growth of melanoma. The findings could open a new
therapeutic area for companies now developing IFN-γblocking antibodies for immune disorders.
Inflaming cardiovascular passions
UCSD and Scripps researchers have linked the heart
disease locus 9p21 to aberrant inflammatory responses
that lead to misregulation of nearby genes. The data could
help differentiate patients whose cardiovascular disease is
likely due to inflammation from patients whose disease is
more likely due to dyslipidemia.
A NAC for TTP
U.S. and Canadian researchers have shown that the
generic drug N -acetylcysteine, which is sold over the
counter for some uses, could potentially be repurposed to
treat thrombotic thrombocytopenic purpura, a hematological disorder for which cumbersome plasma exchange
therapy has been the standard of care for nearly two
decades.
THE DISTILLERY
This week in therapeutics
Sensitizing cancers to Akt inhibitors using EEF2 inhibitors;
treating botulism, malaria and ebola with 1,7bis(aminoalkyl)diazachrysene–based derivatives; using
ATP5O inhibitors to reduce GvHD; and more…
This week in techniques
A synthetic platform for tetracycline analogs; a transgenic
mouse model of diabetes; unnatural amino acid–based
multimeric antibody Fab fragments; and more…
FROM THE MAKERS OF
BioCentury AND nature
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Package deals
Although Gilead isn’t discussing its strategy, Gallagher suggested that, based on her view of its recent deals, the big biotech
might be approaching cancer the same way it did HIV.
“I think they are building a pipeline of key mechanisms that
could some day be combinable,” she said. “Gilead is a believer in
the concept that as we better understand the molecular basis for
cancer — just like HIV — you can target the disease with small
molecules with the objective of having a very clean molecule that
has exposure many-fold above the threshold needed to inhibit the
target, and do it with a therapeutic index that allows for good
tolerability.”
Gallagher pointed to Gilead’s Atripla for HIV, a combination of
its Truvada emtricitabine/tenofovir and Sustiva efavirenz from
Bristol-Myers Squibb Co.
“We might even be able to combine mechanisms, much like
Atripla, by combining a PI3K inhibitor, SYK inhibitor, and another
agent into one tablet that is efficacious, tolerable and convenient,
and thereby make cancer a chronic disease,” she said.
Gallagher said combining the mAb from Arresto with a small
molecule from either Calistoga or CGI, or possibly even both, might
make sense.
“By shutting down the chemokine pathways and getting apoptosis
using something like a PI3K [delta] inhibitor, and then also cutting
off the tumor’s support system in the micro-environment” by
adding a mAb against LOXL2, “could prove very effective for not
only shrinking the tumor but also keeping it from coming back,” she
said.
Astellas Pharma Inc. (Tokyo:4503), Tokyo, Japan
Biogen Idec Inc. (NASDAQ:BIIB), Cambridge, Mass.
Bristol-Myers Squibb Co. (NYSE:BMY), New York, N.Y.
Calistoga Pharmaceuticals Inc., Seattle, Wash.
Diatos S.A., Paris, France
Eli Lilly and Co. (NYSE:LLY), Indianapolis, Ind.
Gilead Sciences Inc. (NASDAQ:GILD), Foster City, Calif.
Jubilant Innovations Ltd., Bangalore, India
Roche (SIX:ROG; OTCQX:RHHBY), Basel, Switzerland
BioCentury
Company Index
February 28, 2011
Abbott A20
ACOSOG A1, A7
ACRIN A4
Advanced BioHealing A16
Alnylam A19
Amgen A2
Apeiron A11
ASCO A19
Astellas A9
Bayer A17
BeiGene A2
Biogen Idec A3, A9
Bristol-Myers A10, A12
CALGB A4
Calistoga A9, A17
Charing Cross Hospital A12
Clinical Data A16
COG A5, A7
Cystic Fibrosis Fndtn A15
Delcath Systems A17
Diatos A9
Dyax A19
ECOG A5
Eisai A11
Eli Lilly A9, A20
Epix A12
Eurofins A17
Forest Laboratories A16
4SC A16
Genentech A4, A9
Georgetown U A4
See page A19
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A11 OF 20
Two for one in neuroblastoma
By Erin McCallister
ment (CRADA).
Senior Writer
In 2009, the COG announced Phase III results that showed
By activating multiple elements of the host’s immune system, ImmRx plus isotretinoin produced significantly higher event-free
Apeiron Biologics AG believes its mAb fused to IL-2 will survival vs. isotretinoin alone after median follow-up of 2.1 years
provide a one-two punch to neuroblastoma cells, without the (66% vs. 46%, p=0.0115). Preliminary two-year survival favored
toxic side effects of systemic IL-2 treatment.
ImmRx plus isotretinoin vs. isotretinoin alone (86% vs. 75%,
The biotech this month obtained rights to develop and p=0.023).
commercialize hu14.18-IL2 from Merck KGaA, which had
However, neither the GM-CSF nor the IL-2 proteins are fused
decided not to develop the candidate due to pipeline prioritization, to the GD2 antibody, resulting in systemic delivery of IL-2.
according to Apeiron CFO Lukas Kadawy.
There were 24 cases of vascular leak reported in the ImmRx
hu14.18-IL2, now called APN301, comprises a mAb against arm and one death due to IL-2 related toxicity vs. 0 cases for
GD2 fused to IL-2. It has completed Phase II testing in neuroblas- isotretinoin monotherapy.
toma.
Accutane isotretinoin from Roche is marketed as an acne
Neuroblastoma is a cancer of the sympathetic nervous system treatment.
that occurs in infants and children, with 650-700 new cases
Because GD2 also is present on melanoma cells, Apeiron may
diagnosed each year in the U.S.
explore development in that cancer. But Schuster expects that
According to Manfred Schuster,
the biotech would need a partner due to
Apeiron’s COO, the standard of care is
the size of the melanoma indication.
“With the GD2 antibody,
chemotherapy plus systemic treatment
While financial details of the Merck
with off-label IL-2. However, IL-2 treatdeal were not disclosed, Kadawy said
we can bring IL-2 to
ment is associated with severe side effects
Apeiron was able to in-license APN301
the place where it is
including vascular leak syndrome.
using the revenues from its 2010 deal with
Marketed IL-2 drugs include Proleukin
GlaxoSmithKline plc.
needed with lower
aldesleukin IL-2 from Novartis AG to
Apeiron received £11 million ($17.6
systemic concentrations.”
treat metastatic melanoma and renal cell
million) up front from the deal, which
carcinoma (RCC), and Ontak denileukin
granted GSK exclusive, worldwide rights
Manfred Schuster, Apeiron
diftitox, an IL-2 plus diphtheria toxin futo APN01. The recombinant angiotensinsion protein from Eisai Co. Ltd. The
converting enzyme 2 (ACE2) has comlatter is approved to treat cutaneous T cell lymphoma (CTCL). pleted Phase I testing to treat acute respiratory distress syn“One of the drawbacks to IL-2 is its dose-related toxicity. But drome (ARDS), and Apeiron CEO Hans Loibner said GSK is
with the GD2 antibody, we can bring IL-2 to the place where it preparing for a Phase II study.
is needed with lower systemic concentrations,” Schuster said.
The upfront included cash and an undisclosed equity investGD2 is a disialoganglioside that is expressed in more than ment. Apeiron is eligible for £207 million ($330.9 million) in
99% of neuroblastoma cells. APN301 binds to the GD2 antigen milestones, plus royalties.
and delivers a dose of IL-2. According to Schuster, this action
Apeiron also used a portion of the GSK revenues to finance
triggers multiple elements of the host’s immune system.
an October deal with Polymun Scientific Immunbiologische
“The antigen is captured by the antibody, which elicits Forschung GmbH, under which Apeiron received exclusive,
effector functions like complement activation and ADCC. But it worldwide rights to Polymun’s recombinant human superoxide
also carries IL-2, which activates immune cells and affects dismutase (SOD), APN201.
macrophages, leading to tumor cell lysis,” he said.
Apeiron is developing APN201 as a topical formulation to
In a single-arm Phase II study in 23 evaluable patients treat skin damage resulting from cancer radiation treatment. The
conducted by the National Cancer Institute’s Children’s biotech expects to start Phase Ib testing in 1H12.
Oncology Group (COG), patients treated with APN301 had a
According to Kadawy, Apeiron expects to in-license “one or
21.7% complete response (CR).
two other things” in the near future in cancer or cancer-related
APN301 also interacts with GD2 expressed in CNS tissues indications.
and peripheral nerves. Kadawy said side effects include joint and
muscle pain, which he said can be managed by slowing the COMPANIES AND INSTITUTIONS MENTIONED
infusion time and co-administration of analgesics.
Apeiron Biologics AG, Vienna, Austria
Apeiron expects to take APN301 into Phase II/III testing this
Eisai Co. Ltd. (Tokyo:4523; Osaka:4523), Tokyo, Japan
year. It is evaluating the trial design, including which, if any,
chemotherapies might be tested in combination with APN301.
Merck KGaA (Xetra:MRK), Darmstadt, Germany
NCI also has combined GD2 and IL-2 to treat neuroblastoma.
Its ImmRx immunotherapy includes ch14.18, a chimeric mAb
against GD2, granulocyte macrophage-colony stimulating factor
Polymun Scientific Immunbiologische Forschung GmbH, Wien,
(GM-CSF) and IL-2. NCI is collaborating on the development and
Austria
commercialization of ch14.18 with United Therapeutics Corp.
under a 2010 Cooperative Research and Development AgreeUnited Therapeutics Corp. (NASDAQ:UTHR), Silver Spring, Md.
BioCentury,
THE
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FEBRUARY 28, 2011
P AGE A12 OF 20
Emerging Company Profile
Karyopharm: Shushing the usher
By Michael Flanagan
Senior Writer
In the battle with the human body’s
natural defense mechanisms, one of the
favorite tricks of tumor cells is to use
karyopherins to usher tumor suppressor
proteins outside the nucleus where they
can no longer regulate the cell cycle, thus
paving the way for unchecked growth and
proliferation. Karyopharm Therapeutics Inc. is developing small molecules
that inhibit karyopherins, which it hopes
will prevent cancer cells from hijacking
the normal cell cycle without the risk of
tumor resistance.
Karyopharm’s lead program targets
exportin 1 (XPO1; CRM1). The company
hopes to enter Phase I testing for severe
hematologic malignancies in 12-24 months.
Tumor suppressor proteins like p53
and retinoblastoma 1 (RB1) and growth
regulatory proteins like p21 are activated
in the nucleus to halt the cell cycle under
conditions common to tumor cells, such
as DNA damage or deregulated oncogene
expression. If the damaged DNA cannot
be repaired, then the proteins induce
apoptosis.
Over the past 10 years, researchers
have shown that “virtually every important tumor suppressor protein is transplanted outside of the nucleus by” XPO1,
CEO Michael Kauffman told BioCentury.
Moreover, he noted that research suggests XPO1 overexpression is correlated
with poor prognosis in ovarian, cervical,
pancreatic and liver cancers, as well as
osteosarcoma and gliomas.
According to Kauffman, cancer cells
should have a hard time developing resistance to XPO1 inhibitors because XPO1
is upstream of most targeted therapies and
affects many different pathways.
XPO1 was isolated in 1990, but
Kauffman said identifying inhibitors proved
hard until researchers found one in
leptomycin B, a naturally occurring antibiotic first isolated from Streptomyces. In a
clinical study by researchers at Charing
Cross Hospital published in the British
Karyopharm Therapeutics
Inc.
Location: Natick, Mass.
Technology: Small molecule modulators of nuclear transport
Disease focus: Cancer, inflammation,
infectious disease
Clinical status: Preclinical
Founded: 2008 by Sharon Shacham,
Michael Kauffman, Ronald DePinho
and Giulio Draetta
University collaborators: Multiple academic institutions
Corporate partners: None
Number of employees: 9
Funds raised: $21.5 million
Investors: Chione Ltd. and angel investors
CEO: Michael Kauffman
Patents: None
Journal of Cancer in 1996, the compound
showed some anti-cancer properties, but
off-target effects caused severe diarrhea
and fatigue.
Kauffman said Kosan Biosciences Inc.
was the only company he knew of that had
looked into designing leptomycin B analogs, but the program had been shelved
before Kosan was bought by BristolMyers Squibb Co. in 2008 (see
BioCentury, June 2, 2008).
Karyopharm has taken a different approach. CSO and Head of R&D Sharon
Shacham used in silico modeling to discover drug-like molecules that appeared
to be much more specific for XPO1 than
leptomycin B. “We modified and optimized these, filed some patents, and formed
the company based on them,” Kauffman
said.
Shacham helped invent the discovery
software when she was SVP of drug development at Predix Pharmaceuticals Inc.
(now Epix Pharmaceuticals Inc.).
Predix used the software to identify at
least four small molecules that were taken
into clinical testing.
Karyopharm’s XPO1 inhibitors kill tumor cells rapidly and with high potency
and selectivity in a variety of in vitro cancer
models, according to Kauffman. The company is waiting until its patent applications
have been issued to publish the data, he
said.
Kauffman said that virtually every hematological malignancy has been susceptible within 48 hours of administration —
including myeloma, lymphoma and leukemia. Solid tumor cells also were killed,
though it took 24 hours longer.
“One of the things that we have shown
is that normal cells don’t mind it when you
block the transport of the tumor suppressor
proteins,” he said. Unlike tumor cells, which
have been shown to undergo apoptosis
within 48-72 hours, healthy cells temporarily undergo cell cycle arrest and stop
dividing, but soon return back to normal.
“In mice, we’ve shown that we can
inhibit the growth of a variety of tumors
without any tolerability issues” such as
the severe diarrhea and fatigue caused by
leptomycin B, said Kauffman.
With preclinical data in hand last year,
Karyopharm closed a $20 million series A
round that should last through the completion of the company’s first Phase I trial in
advanced hematological malignancies.
Once a dose range is established in the
initial study, “we are likely to get a solid
tumor study up and running as well,”
Kauffman said.
Karyopharm also has discovery programs focused on other karyopherins,
which Kauffman said may have potential
for inflammatory and infectious diseases.
Bristol-Myers Squibb Co. (NYSE:BMY),
New York, N.Y.
Charing Cross Hospital, London, U.K.
Epix Pharmaceuticals Inc. (Pink:EPIX),
Lexington, Mass.
Karyopharm Therapeutics Inc., Natick,
Mass.
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THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A13 OF 20
Finance
Virtue in virtual
By Stacy Lawrence
entity. Each structure will have a CMO, but no other dedicated
Senior Writer
management. To plan and execute clinical development, AVDC
Atlas Venture is looking to build a pipeline, rather than will rely on direction from a network comprising “every single
companies, with its new Atlas Venture Development Corp. Atlas network contact with information on a particular indicainitiative. Through AVDC, Atlas will develop clinical candidates tion or asset,” he said.
and then sell or partner them without the traditional trappings
Formela said AVCD’s first deal, which is still in progress and
that go with company formation.
is not disclosed, exemplifies the approach. “The target was
The model promotes capital efficiency, a long-standing pursued by 2-4 companies. We’re working with one to farm it
buzzword among VCs that has taken on real meaning in this out,” into a holding structure.
economic climate. Given a listless IPO market, lower returns and
He added: “There are two other people who are no longer
an increasing cost of capital, life science VCs like Atlas are working on the target who are free to help benchmark it across
looking for creative ways to make more of what they’ve got.
all the related assets,” on the same target.
“We’re trying to promote both capital efficiency and velocity
The virtual team will be paid in cash and equity, but will not
with an asset-centric model,” Partner Jean-Francois Formela told work on the project full time. “We are renting, rather than
Ebb & Flow.
buying,” said Formela.
Atlas expects to do two or three AVDC
The firm has negotiated term sheets for
deals this year, starting next quarter. The
two deals and is in transaction discussions
“We believe we can get to
firm has reserved an undisclosed portion
for two or three more candidates. To get
POC for $12-$15 million on
of its eighth fund specifically to invest in
there, Atlas evaluated about 150 proAVDC. The fund closed at $283 million in
grams, entered confidential disclosure
average, all included, if you
2009 (see BioCentury, Feb. 2, 2009).
agreements on 30 and completed due
select the right programs. If
Formela noted VCs have long bandied
diligence on about 15.
about the notion of virtual companies.
Atlas is turning to pharma companies
you can do that, you should
But, he said, when capital was abundant,
because they have assets but can’t afford
the model was suspect.
to move every promising program into full
be able to generate venture
“I had been quoted in the ‘90s as
development.
returns with this model.”
saying, ‘Virtual investments lead to virtual
“Pharma has seen an increase in its
returns’,” Formela said. “Back then, comearly pipeline, pre-IND and Phase I. But
Jean-Francois Formela,
panies typically stayed virtual when they
the cost of late-stage development and
Atlas Venture
couldn’t raise money. Because capital was
commercialization has gone higher and
plentiful, if a company was virtual that
higher, driven in part by rising safety
wasn’t a good sign.”
hurdles,” Formela noted.
But this is clearly not that economy.
In some of the deals, pharmas still may help fund developVenture returns and fundraising remain muted. The closely ment, as Formela noted “companies most interested in
watched 10-year returns for venture capital funds were -4.6% at externalization are willing to allocate some of their budget
Sept. 30, according to Cambridge Associates. That’s worse than toward externalization.”
the performance over the same period of the NASDAQ (-4.3%)
Formela said accounting rule FIN 46(R) from the Financial
and S&P 500 (-0.4%).
Accounting Standards Board (FASB) means companies need to
In the third quarter, Cambridge Associates calculated that be “very careful about consolidation.”
healthcare venture capital generated less than half the returns —
FIN 46(R) requires a company to consolidate a related entity
3.5% — of venture capital invested in software (7.7%), IT (7.3%) onto its balance sheet if the company has a controlling financial
or energy (7.2%).
interest, which is not limited to equity ownership and voting
Last year, 157 U.S. venture firms raised $12.3 billion, accord- rights but may include things like entitlement to residual returns,
ing to Thomson Reuters and the National Venture Capital and obligations to accept losses.
Association. That’s only 39% of the $31.9 billion raised by 235
“Different CFOs will have different levels of tolerance,” said
U.S. firms in 2006. The peak of venture fundraising was in 2000 Formela. “Perhaps the structure of the deal will have to be
at nearly $100 billion.
different based on their sensitivity to consolidation.”
He expects the accounting issues will become easier to
address as companies become more familiar with the AVDC
Advising AVDC
structure.
“The thing we’ve learned is that because the structure is
Beyond the pressures on private and public biotech investors, Formela now sees several factors favoring the virtual model. novel, a lot has to do with mutual understanding and trust,” he
Among these are improved outsourcing capability for everything said. “Once we agree on core intents, it becomes easier to
from trial design to formulation to manufacturing, and budgetary structure the relationship despite potential complexity.”
The venture firm isn’t particularly interested in the candiconstraints and pipeline needs within pharma.
AVDC will take early stage assets from pharma companies dates that a pharma might be “ready and willing to externalize.
See next page
and spin them into individual “structures” within a holding
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A14 OF 20
Finance,
from previous page
We’re interested in the one they have a tough time giving up but
that doesn’t make the budget,” said Formela. “Historically, many
assets that are readily disclosed and offered for out-licensing are
typically the dogs.”
Formela’s also skeptical of the traditional spin-off model, in
which a pharma lops off several candidates to form a newco.
“Historically, venture guys thinking about a spin-off would
have been excited to announce a Pfizer spin-off with many
molecules and $50-$75 million. We’re looking at that today and
scratching our heads,” he said. “To identify more than one
winning asset in one defined pool has essentially been impossible.
I would want to be shown spinouts where every single molecule
and program deserves financing on a stand-alone basis.”
BioCentury
The ROI
Chicago: +1 312-755-0798; Fax: +1 312-755-0658
The anemic IPO market is also a strong impetus behind the
new vehicle. Through AVDC, Atlas is developing assets for M&A.
“We need a different structure to do that,” said Atlas
Managing Director David Grayzel, who is managing director at
AVDC.
Formela added an IPO “is a last resort right now, as investors
will typically take a tremendous haircut that will probably wipe
out returns.”
In contrast, he said it’s possible to get a price range of about
$150-$400 million for an asset with Phase II proof-of-concept
data, depending on the indication.
“A lot of deals are seeing $150-$250 million up front and
another 2X-plus on top of that if you get approval,” he said.
“We believe we can get to POC for $12-$15 million on
average, all included, if you select the right programs. If you can
do that, you should be able to generate venture returns with this
model. Of course not every candidate is going to get to the full
POC I’m describing,” he said.
Atlas is flexible on the types of deals. Some will be structured
as single asset spinouts, while others will include a buyback
option, and still others will allow the pharma to retain the
candidate and simply contract out development.
In the latter scenario, AVDC would function as “almost a
venture service company,” between pre-IND and POC, said
Formela.
“We believe that we can structure success fees and milestones in a way that produces venture returns and yet gives
pharma a more cost-efficient way to access/opt-in on POC
programs,” he added.
The expectations are not limited to the idea that the investment threshold be lower to get to the same POC result. Without
a management team and a corporate structure, it will be much
easier to kill projects that aren’t working.
“Not only can we be more efficient for fully funded programs,
but we can be more rigorous about early kills,” said Grayzel.
“Sometimes the goal of company building can distract you away
from running a killer experiment. And it can be a big challenge
when those don’t have positive data.”
Formela concurred: “In the traditional, old-school model,
attrition costs are piling up. Here attrition is costing less money
because you’re always going for the quick kill.”
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BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A15 OF 20
Ebb & Flow
Vertex erects its pillars
By Stacy Lawrence
regulatory authorities how to move forward on testing the
& Stephen Hansen
compound in patients with those mutations.
Staff Writers
Vertex expects to report data this half from a Phase IIa
Vertex Pharmaceuticals Inc. (NASDAQ:VRTX) gained combination trial of VX-770 and another CF candidate, VX-809.
$1.2 billion in market cap last week on positive Phase III data for The study is in adult patients with the F508del mutation, the most
VX-770 to treat cystic fibrosis. The data sent shorts running for common CF mutation.
cover and gave room for optimists to run.
VX-770 aims to increase the function of defective CFTR
The shares climbed $5.75 (15%) to $43.97 on Wednesday on proteins by increasing the gating activity of CFTR at the cell
the news that the compound met the primary endpoint in the surface — the ability to transport ions across the cell membrane.
STRIVE trial in patients with at least one copy of the G551D VX-809 is a CFTR corrector that aims to increase CFTR function
cystic fibrosis transmembrane conductance regulator mutation. by increasing the trafficking of CFTR to the cell surface.
The CFTR potentiator significantly improved mean absolute
About 48% of CF patients in the U.S. have two copies of the
change in forced expiratory volume in one second (FEV1) from F508del mutation, while another 39% have one copy, according
baseline to week 24.
to the Cystic Fibrosis Foundation.
“We believe that a corrector compound [VX-809] may allow
The price move “was partially short covering,” Sven Borho of
OrbiMed Advisors told Ebb & Flow. “The Street consensus more functioning CFTR to get to the cell surface,” said Mueller,
amongst hedge funds is to short every stock just around the new who said the data for the potentiator VX-770 “may help that
corrective CFTR protein work better once
product launch. But in this case hedge
it reaches the surface.”
funds were also shorting ahead of the CF
Money Raised in 2011
While the combination trial is primadata.”
rily a safety study, Mueller said, “we hope
The short interest in Vertex at Jan. 31
Last week, the biotech industry raised $195
also to see some signal that we are increaswas 13.1 million shares (6.5% of outstandmillion, bringing to $4.3 billion the total raised
ing CFTR function.”
ing shares), up from 11.9 million on Jan.
year-to-date. In 2010, a total of $36.1 billion was
14.
raised, including $1.6 billion in IPOs, $3.5 billion
But, Borho added, “the jump in share
in follow-ons, $5.4 billion in venture capital, and
Doing the math
price was not just short covering. This
$25.6 billion in other fundraising. Totals include
was also a reflection of the new second
The CF population is about 30,000 in
overallotments and warrants, and are rounded to
pillar in the Vertex story.”
the U.S., with about 70,000 patients glothe nearest millions.
Vertex’s telaprevir to treat HCV has a
bally. That would mean about 1,200 U.S.
May 23 PDUFA date.
patients with the G551D mutation and
Vertex expects results mid-year from
about 2,800 globally.
another trial of VX-770, the Phase III
Using 3,000 patients and a $250,000
ENVISION trial in patients ages 6-11 with
price, in line with other ultra-orphan drugs,
at least one copy of the G551D mutation.
Mark Schoenebaum of ISI Group pegs peak
The company plans to submit regulatory
sales for this indication at $550 million.
applications in the U.S. and EU in 2H11 to
He estimated that associated costs
treat CF patients with the G551D mutawould be only $30 million, because it’s a
tion.
small molecule.
That cohort represents about 4% of
Vertex started its CF program in 1998
the CF population in the U.S. But the
as part of a collaboration with CFFT, the
potential to expand the treatment populaSource: BCIQ: BioCentury Online Intelligence
non-profit drug discovery and develoption also caught investor interest.
ment affiliate of the Cystic Fibrosis FounVertex could “hit multiple different
dation. If VX-770 is approved, CFFT will
specific patient populations with one or
receive single-digit royalties from Vertex.
more compound, addressing one of the
“This is a nice example of how patient
most active patient populations of any
groups can impact the development proorphan disease,” said Andrew Bogan of
cess,” said Bogan. “It’s very clear that
Bogan Associates.
Vertex would not have done this without
funding from the Cystic Fibrosis Foundation.”
770 + 809
Vertex shares were up $5.68 (15%) to
$44.84 on the week.
On a conference call about the data,
EVP of Global R&D and CSO Peter Mueller
said the company has in vitro data showing
Not another Savient
that VX-770 may work in other CF mutations with reduced or low channel gating.
Investors who had fantasized about a
Source: BCIQ: BioCentury Online Intelligence
See next page
He said the company would discuss with
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
Ebb & Flow,
from previous page
stratospheric sale price for Clinical Data Inc. (NASDAQ:CLDA)
were brought down to earth last week, as the company said it
would be acquired by Forest Laboratories Inc. (NYSE:FRX)
for $30 per share in cash, plus a contingent value right worth up
to $6 based on sales milestones
of depression drug Viibryd
“The fantasy
vilazodone.
Shares of Clinical Data fell
price for CLDA
$2.69 to $31.21 on Tuesday
was $40-$50.”
and closed the week down
$3.60 (11%) at $30.30.
Sven Borho,
After Viibryd was approved
OrbiMed Advisors
by FDA in February, the company said it was considering
selling the company or finding a partner for Viibryd.
Investors apparently expected the company would be sold,
given that Chairman Randall Kirk had been chairman of New
River Pharmaceuticals Inc. when it was acquired by Shire plc
(LSE:SHP; NASDAQ:SHPGY) for $2.6 billion in cash in 2007.
Clinical Data closed at $15.03 on Jan. 21, the last trading day
before FDA approved Viibryd.
“Everyone was recollecting Kirk’s acumen in selling New
River. The share price ran ahead of itself on M&A rumors,” said
Sven Borho of OrbiMed Advisors. “The fantasy price for CLDA
was $40-$50.”
Once the company said it was potentially for sale, Borho
argued that it was stuck. “What was the alternative? If it had
raised capital and launched the drug, the stock would have been
at $15. Just look at the case of Savient,” he said.
Savient Pharmaceuticals Inc. (NASDAQ:SVNT) lost more
than half its value after it put itself up for sale following approval
of Krystexxa pegloticase for gout, but was unable to find an
acquirer (see BioCentury, Feb. 7).
“I think it’s smart what CLDA did in the end. If any shareholders fault them for it, that’s foolish,” Borho said. “They preserved
a lot of shareholder capital by not being too greedy on the price.”
The upfront portion represents about $928.6 million, based
on 31 million shares outstanding on Feb. 8, and is a 67% premium
to Clinical Data’s close before FDA approved Viibryd.
Forest expects to launch the mixed selective serotonin
reuptake inhibitor (SSRI) and partial serotonin (5-HT1A) receptor agonist next half.
Its shares lost $2.45 to $31.88 on the week.
Outside the family
With important Phase IIb data expected next quarter for lead
compound vidofludimus (4SC-101), 4SC AG (Xetra:VSC) raised
€11.7 million ($16.1 million) last week in a private placement.
CEO Ulrich Dauer said the financing fulfilled two purposes:
diversifying the shareholder base and strengthening the balance
sheet prior to any licensing negotiations.
Dauer said the previous shareholder structure was dominated by two family-based investors who held a combined 64.5%
of the company. 4SC wanted to bring in more institutional life
science players, with an emphasis on U.S.-based investors.
4SC sold 3.5 million shares at €3.40, a 5% discount to the
close of €3.58 on Feb. 23, the day before the deal was proposed.
“A significant portion of this money came from U.S.-based
investors”, Dauer told Ebb & Flow.
FEBRUARY 28, 2011
P AGE A16 OF 20
The deal reduces the stake of 4SC’s largest investor, Santo
Holding, from 48.1% to 44.1%. The stake held by the secondlargest shareholder, FCP Biotech Holding GmbH, moves from
16.4% to 15%.
With data from the Phase IIb COMPONENT trial of
vidofludimus for rheumatoid arthritis (RA) expected next quarter, Dauer said, it was important to strengthen the balance
“A significant
sheet before negotiating to
partner the compound before
portion of this
entering Phase III testing.
“It’s easier to do those kind
money came
of negotiations when you can
from U.S.-based
show some strength on the
balance sheet rather than if
investors.”
you are desperate for cash,” he
said.
Ulrich Dauer, 4SC AG
Vidofludimus is a small
molecule inhibitor of dihydroorotate dehydrogenase (DHODH)
and IL-17.
4SC has a monthly burn rate of about €1.5 million ($2.1
million). The most recently reported cash figure was €22.2
million ($30.2 million) at Sept. 30, putting the company’s current
cash at around €14.7 million ($20.1 million) pre-deal and at
about €26.4 million post-deal.
That’s enough to reach the end of 2012, by which time the
company will have readouts from two Phase II trials of its second
most advanced compound, resminostat (4SC-201), in hepatocellular carcinoma (HCC) and Hodgkin’s lymphoma. Resminostat is
a pan-histone deacetylase (HDAC) inhibitor.
4SC finished the week down €0.46 (12%) to €3.50.
Dermagraft redux
Profitable wound healing play Advanced BioHealing Inc.
proposed late Friday to raise up to $200 million in an IPO.
The company markets Dermagraft, a human fibroblast-derived skin substitute, to treat full-thickness diabetic foot ulcers.
Last November, Advanced BioHealing completed enrollment
in a pivotal trial of Dermagraft in venous leg ulcers. It expects
data this year, and hopes to submit a supplement to the existing
PMA in 1Q12. FDA denied approval for Dermagraft to treat
venous leg ulcers in 2005.
The company’s TransCyte for full and partial thickness burns
was approved by FDA in 1997, but has yet to be marketed.
Advanced BioHealing hopes to create arrangements to market
TransCyte to U.S. state and federal as well as international
government agencies.
The company had $146.7 million in revenue last year, with
operating income of $20.9 million. At Jan. 1, the company had
$22.5 million in cash and $14.2 million in a revolving line of
credit.
Advanced Tissue Sciences Inc. and partner Smith & Nephew
plc (LSE:SN; NYSE:SNN) developed Dermagraft and TransCyte.
When Advanced Tissue declared bankruptcy in 2002, Smith &
Nephew acquired the products and related assets for $7 million.
In 2006, Advanced BioHealing purchased the assets for an
undisclosed amount. Some of the patents have expired and the
remainder are slated to do so from 2012-18.
Advanced BioHealing expects to use part of its IPO proceeds
to in-license or acquire complimentary products.
Investors include Canaan Partners (40.7% pre-IPO stake);
See next page
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A17 OF 20
Earnings on deck
At least three profitable biotechs and pharmas are slated to report earnings this week. Endo Pharmaceuticals Holdings Inc. (NASDAQ:ENDP) is expected
to report a 19% increase in EPS on revenues of $482.8 million. The company, which sells neurology drugs such as Lidoderm lidocaine topical patch
to treat post-herpetic neuralgia (PHN), reported sales of $391.4 million in 4Q09. In January, UCB Group (Euronext:UCB) said it expects FY10 revenue
and core EPS to exceed its prior guidance of at least €3 billion ($4 billion) and €1.76, respectively. (A) FY09 core EPS figure
Company
Date
Pre/post mkt
Bayer AG (Xetra:BAY)
2/28
Pre
€0.95
€ 0.90
6%
Endo Pharmaceuticals Holdings Inc. (NASDAQ:ENDP)
2/28
Post
$0.96
$0.81
19%
UCB Group (Euronext:UCB)
3/2
NA
NA
€1.25 (A)
NA
Ebb & Flow,
from previous page
Safeguard Scientifics Inc. (28.1%); and Wheatley Partners (14.7%).
Underwriters are BofA Merrill Lynch; JPMorgan; Wells Fargo;
William Blair; and Oppenheimer.
Regulatory milestones
Delcath Systems Inc. (NASDAQ:DCTH) fell $4.29 (38%)
to $7.01 on Tuesday after FDA refused to file an NDA for
melphalan delivered using the Delcath Percutaneous Hepatic
Perfusion (PHP) System to treat melanoma metastatic to the liver.
The agency requested information about the timing of manufacturing plant inspections and product and sterilization validations, as well as additional safety information and statistical
analyses. Delcath lost $5.01 (44%) to $6.29 on the week.
Look for shares of Ligand Pharmaceuticals Inc.
(NASDAQ:LGND) to move this week after partner
GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) reported late
Friday that FDA granted full approval for Promacta eltrombopag
to treat chronic idiopathic thrombocytopenic purpura (ITP) in
patients who have an insufficient response to corticosteroids,
immunoglobulins or splenectomy. The drug received accelerated approval from FDA in 2008. GSK has worldwide rights from
Ligand, which gained $0.10 to $10.08 last week.
Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) was
off $0.48 to $37 last week after submitting a BLA to FDA for
VEGF Trap-Eye to treat wet age-related macular degeneration
(AMD). The biotech requested Priority Review. Partner Bayer
AG (Xetra:BAY) plans to submit a regulatory application in
Europe this half.
Salix Pharmaceuticals Ltd. (NASDAQ:SLXP) fell $9.84
(24%) to $31.61 on Thursday after saying it expects to receive
a complete response letter for Xifaxan rifaximin 550 mg tablets
based on a telephone conversation with FDA about the irritable
bowel syndrome (IBS) candidate. Salix attributed the expected
setback to FDA’s “newly expressed need for retreatment information.” The PDUFA date for the sNDA is March 7. Salix was off
$10.18 (23%) to $33.49 on the week.
Sosei Group Corp. (Tokyo:4565) lost ¥12,400 to ¥139,000
last week after Japan approved NorLevo levonorgestrel as an
emergency contraceptive.
Clinical milestones
Medivir AB (SSE:MVIR B) was off SEK0.75 to SEK139.50 last
week after reporting additional data from the Phase IIb PILLAR
(TMC435-C205) trial showing that 76-84% of HCV patients in
4Q10 EPS est
4Q09 EPS
Expected chg
the four TMC435 regimens achieved a sustained virologic
response (SVR). The ongoing, double-blind, placebo-controlled,
international trial enrolled 386 treatment-naive patients with
chronic HCV genotype 1 infection (see B15).
Ebb & Flow
Gilead Sciences Inc. (NASDAQ:GILD) lost $0.29 to
$39.01 last week after saying it plans to acquire cancer and
inflammation company Calistoga Pharmaceuticals Inc. for
$375 million in cash, plus up to $225 million in milestones (see
“Gilead’s Cancer Encore,” A9).
Infectious diseases company Intercell AG (VSE:ICLL;
OTCQX:INRLY) lost €0.45 to €9.25 last week after raising €33
million ($45.2 million) in a bumped-up private placement of 6%
senior unsecured convertible notes due 2014.
ProStrakan Group plc (LSE:PSK) gained 22.60p (21%) to
131.50p on Monday after Kyowa Hakko Kirin Co. Ltd.
(Tokyo:4151) said it will acquire the company for 130p per
share, or about £292 million ($474 million) in cash. Kyowa said
the acquisition will provide an established EU and U.S. sales
force. It also will gain ProStrakan’s specialty pharmaceutical
products, including pain drug Abstral fentanyl. ProStrakan was
up 23.62p (22%) to 132.37p last week.
Quest Diagnostics Inc. (NYSE:DGX) lost $0.89 to $56.67
last week after announcing plans to buy the Athena Diagnostics
Inc. unit of Thermo Fisher Scientific Inc. (NYSE:TMO) for
$740 million. Thermo Fisher also plans to sell its Lancaster
Laboratories Inc. contract testing unit to Eurofins Scientific
S.A. (Euronext:ERF) for $200 million. Eurofins was up €2.63 to
€55.27 on the week.
Theratechnologies Inc. (TSX:TH) was off C$0.23 to C$4.78
last week after the endocrine and pulmonary company announced plans to sell 11 million shares in a listing on NASDAQ.
Transgene S.A. (Euronext:TNG) fell €2.80 (19%) to €12
on Wednesday after Roche (SIX:ROG; OTCQX:RHHBY) terminated a 2007 deal and returned rights to TG4001 (RG3484) for
HPV-mediated diseases. The compound is in Phase IIb testing.
According to Transgene, Roche said the decision was strategic
and not “data-driven.” Transgene was off €2.67 (18%) to €12.18
on the week.
— Staff Writer Andrew Fisher contributed to this week’s Ebb &
Flow
Stay Alert with BioCentury:
A New Custom Publications Alert Service
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A18 OF 20
EPS watch
At least seven profitable biotechs and pharmas reported earnings last week. Antibody play MorphoSys AG (Xetra:MOR) fell 4% last week after reporting
FY10 EPS was unchanged vs. 2009 and announcing that CFO Dave Lemus is stepping down. Lemus will be replaced by Jens Holstein, a regional CFO
for Europe and the Middle East at the Fresenius Kabi AG subsidiary of Fresenius SE (Xetra:FRE). Morphosys also raised its FY11 revenue and operating
profit guidance. Mcap in $M
Company
Bio-Rad Laboratories Inc. (NYSE:BIO)
4Q10
EPS est
4Q10
EPS actual
$1.35
$2.17
Outcome
Beat by $0.82
Growth
from 4Q09
46%
2/25
cls
Wk
chg
% chg
Mcap
chg
2/25
Mcap
$113.47
$3.57
3%
$99.3
$3,155.4
4Q10 revenue for the tool supplier was $533.7M, up 8% from $495.1M. The Street was expecting $514.5M. Sales from the companys clinical diagnostic segment increased 12% in 4Q10 to $336.5M
Merck KGaA (Xetra:MRK)
NA
€1.78
NA
87%
€65.08
€2.38
4%
$708.8 $19,380.9
4Q10 total revenue grew 26% to €2.5B ($3.4B) from €2B in 4Q09. The pharma expects FY11 revenues to grow 13-18% over FY10.
MorphoSys AG (Xetra:MOR)
NA
NA
NA
NA
€19.11
-€0.79
-4%
-$38.3
$570.1
FY10 EPS was €0.40, same as FY09. 4Q10 revenue was €24.3M ($32.4M), up 4% from €23.4M in 4Q09. The company raised its FY11 revenue and
operating profit guidance to €105-€110M from €105M and to €10-€13M from €10M.
Ranbaxy Laboratories Ltd.
(NSE:RANBAXY; BSE:500359)
NA
NA
NA
NA
Rs449.15
-Rs57.15
-11%
-$534.5
$4,200.4
While Ranbaxy did not report 4Q10 figures, the Indian pharmas FY10 net income of Rs15.0B ($333.8M) was less than the Rs15.9B ($355.5M) recorded
for the first nine months of 2010, indicating a loss in 4Q10. Ranbaxy recorded a Rs1.8B ($40.5M) charge in 2010 related to the impairment in goodwill
in its subsidiaries. FY10 global sales were Rs85.5B ($1.9B), up 23% from Rs73.4B ($1.5B) in FY09. U.S. sales rose 80% to Rs27.4B ($600M). The
company expects FY11 base case sales to be about Rs84B ($1.9B).
Talecris Biotherapeutics Inc.
(NASDAQ:TLCR)
$0.38
$0.38
Met
73%
$24.92
-$0.58
-2%
-$72.8
$3,128.2
4Q10 non-GAAP EPS figure excludes a $0.05 per share charge for costs related to Talecris merger agreement with Grifols S.A. (Madrid:GRF) and a
$0.20 per share charge related to a breach of contract lawsuit ruling with Plasma Center of America. 4Q10 revenue was $410.8M, up 5.3% from
$390.1M in 4Q09.
Valeant Pharmaceuticals International Inc.
(NYSE:VRX; TSX:VRX)
$0.45
$0.51
Beat by $0.06
-39%
$40.11
-$0.36
-1%
-$108.7 $12,113.4
4Q09 figures for the company, which was formed from the Sept. 2010 merger between Biovail Corp. and Valeant Pharmaceuticals International, do
not include revenue from Valeant Pharmaceuticals International. Total revenue in 4Q10 was $514.6M, up 113% from $241.1M in 4Q09. The company
increased its FY11 EPS guidance to $2.45-$2.70 from $2.25-$2.50.
ViroPharma Inc. (NASDAQ:VPHM)
$0.31
$0.44
Beat by $0.13
144%
$17.53
$0.23
1%
$18.0
$1,368.2
Net product sales increased 38% in 4Q10 to $121.6M from $87.8M in 4Q09. Sale of hereditary angioedema (HAE) drug Cinryze were $52.5M for the
quarter, up 46% from 4Q09. The biotech reiterated FY11 Cinryze sales guidance of $235-$260M.
Online links this week
Links to the following documents reside online on the BioCentury on
BioBusiness page of www.biocentury.com.
Biosimilars
CHMP draft concept paper for the revision of guidelines for quality
requirements of biosimilar products.
Drug safety
FDA draft guidance on the use of medication guides, which aim to
alleviate the burden of REMS on companies and the agency (see
BioCentury Extra, Friday, Feb. 25).
EMA
— EMA statement of revenue and expenditure for 2011.
— EMA Joint CHMP/CVMP Quality Working Party work plan for
2011.
Geriatrics
EMA strategy for developing medicines for the elderly.
Health reform
Letter from Chairman Fred Upton (R-Mich.) and other Republican
members of the House Committee on Energy and Commerce
seeking information about meetings the White House Office for
Health Reform held with industry groups (see BioCentury Extra,
Wednesday, Feb. 23).
Heparin
Letter to FDA from Chairman Fred Upton (R-Mich.) and other
Republican members of the House Committee on Energy and
Commerce requesting information related to the 2008 heparin
contamination incident (see BioCentury Extra, Thursday, Feb. 24).
HIV
CHMP draft concept paper on guidance for the non-clinical and
clinical development of medicinal products to prevent HIV infection.
See next page
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
FEBRUARY 28, 2011
P AGE A19 OF 20
Analyst picks & changes
Company
Bank
Analyst
Coverage
Opinion
Alnylam Pharmaceuticals Inc.
(NASDAQ:ALNY)
Needham
Alan Carr
Upgrade
Buy (from hold)
Wk chg
2/25 cls
0%
$11.36
Carr upgraded based on newsflow from the companys clinical pipeline in 2011 and low valuation that is only modestly above cash. He
expects final Phase I data for ALN-VSP in liver cancer to be presented at the American Society of Clinical Oncology (ASCO) meeting in June
and Phase I data for ALN-TTR01 to treat transthyretin amyloidosis in 3Q11. ALN-VSP is a lipid nanoparticle formulation of two short
interfering RNAs that target the kinesin spindle protein (KSP) and VEGF genes. ALN-TTR01 is a stable nucleic acid lipid particle (SNALP)formulated RNAi targeting the transthyretin (TTR) gene. Carr also expects four programs to be in the clinic by mid-year.
Dyax Corp. (NASDAQ:DYAX)
Needham
Mark Monane
Price target
Buy
-11%
$1.72
Monane lowered his target to $4 from $8 after Dyax reported $3M in 4Q10 sales for hereditary angioedema (HAE) drug Kalbitor ecallantide, below
his estimate of $4.6M. He remains encouraged by managements strategy to grow the acute HAE market and the continued increase in patients
treated/re-treated with the yeast-derived recombinant plasma kallikrein inhibitor, but has lowered his expectations for the near-term. He lowered his
FY11 and FY12 revenues estimates to $43M and $70M, respectively, from $60M and $112M.
Vertex Pharmaceuticals Inc. (NASDAQ:VRTX)
Baird
Thomas Russo
Price target
Market outperform
Leerink
Howard Liang
Price target
Market outperform
Piper Jaffray
Edward Tenthoff
Price target
Overweight
15%
$44.84
Russo raised his target to $52 from $47 after Vertex reported that oral VX-770 met the primary endpoint in the Phase III STRIVE trial to treat cystic
fibrosis in patients carrying the G551D mutation in cystic fibrosis transmembrane conductance regulator (CFTR) on at least one allele. Vertex plans to
submit regulatory applications in the U.S. and Europe for the small molecule potentiator of CFTR next half (see Vertex Erects its Pillars, A15).
Liang raised his target to $56 from $48 on the VX-770 news. He believes the data supports premium pricing for the ultra orphan indication of G551D
patients, which could be a significant revenue opportunity.
Tenthoff raised his target to $52 from $48 on the VX-770 news. He anticipates a launch in 2012.
Online Links,
from previous page
sible agents included on SPCs for plasma-derived medicinal products.
Orphan drugs
U.S. Supreme Court opinion in Bruesewitz v. Wyeth, which ruled 62 that the National Childhood Vaccine Injury Act of 1986 “preempts all design-defect claims against vaccine manufacturers brought
by plaintiffs seeking compensation for injury or death caused by a
vaccine’s side effects” (see BioCentury Extra, Tuesday, Feb. 22).
Vaccines
— Summary of actions taken at the Feb. 8-9 plenary meeting of
EMA’s COMP.
— Pharmaceutical Research and Manufacturers of America
(PhRMA) report listing 460 products in clinical development to
treat or prevent rare diseases, up from 303 products in 2007 (see
BioCentury Extra, Friday, Feb. 25).
Pharmacogenomics
FDA draft guidance on early phase clinical trial design for evaluating
pharmacogenomics.
Pharmacovigilance
Summary of actions taken at the Feb. 14-16 plenary meeting of
CHMP’s Pharmacovigilance Working Party (PhVWP).
Plasma-derived products
CHMP draft guideline for texts and warning statements on transmisCompany Index,
from page A10
Gilead A9, A17
GlaxoSmithKline A2, A11, A17
GOG A7
Gynecologic Oncology Group A5
Institute of Medicine A2, A7
Intercell A17
J&J A2, A20
Jubilant A9
Karyopharm A12
Kyowa Hakko Kirin A17
Ligand A17
Medivir A17
Merck KGaA A11
National Cancer Inst A11
NCCTG A5
NCI A1, A7
New York U A20
Nodality A3, A7
Novartis A3, A11
NSABP A5
Oregon Health & Science U A2
Product documentation
— Alimta: CHMP revised an EPAR updating SPC to include
information about Stevens-Johnson syndrome, toxic epidermal
necrolysis, sepsis and hemolytic anemia for Alimta pemetrexed to
treat pleural mesothelioma and non-small cell lung cancer (NSCLC);
from Eli Lilly and Co. (NYSE:LLY).
— Humira: U.S. Court of Appeals for the Federal Circuit ruling that
patents co-owned by New York University and Johnson &
Johnson (NYSE:JNJ) covering the use of antibodies against TNF
alpha are invalid and therefore not infringed by autoimmune drug
Humira adalimumab; from Abbott Laboratories (NYSE:ABT)
(see BioCentury Extra, Wednesday, Feb. 23).
Pfizer A14
PhRMA A20
Polymun Scientific A11
ProStrakan A17
Quest Diagnostics A17
Regeneron A17
Roche A9, A11, A17
RTOG A5, A7
Salix A17
Savient A16
Shire A16
Smith & Nephew A16
Sosei A17
SWOG A5, A7
Theratechnologies A17
Thermo Fisher Scientific A17
Transgene A17
Tufts Medical Center Cancer Center A5
United Therap A11
U of California, San Francisco A4
U of Michigan Comprehensive
Cancer Center A5
Vertex A15, A19
BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
BioCentury 100 Price & Volume Trend
Cumulative weekly performance of 100 bioscience stocks. 12-week period.
Line shows Price Level change (Left scale. Index base=1000 on May 10,
1996). Bars show cumulative volume in millions (right scale).
FEBRUARY 28, 2011
P AGE A20 OF 20
Price Gains
Stocks with greatest % price increase in the week ended Feb. 25.
(Priced above $2; 5,000 minimum share volume)
Company
Ticker
$Close
$Chg %Chg Vol(00)
4.520
0.950
27%
20338
Transition Therap1 TTHI
ProStrakan
PSK
132.4p
23.6p
22% 234534
Siga
SIGA
13.400
2.000
18%
34806
Achillion
ACHN
5.850
0.870
17%
13547
Stentys
STNT
€14.050 €2.050
17%
848
Apricus Biosciences APRI
5.130
0.740
17% 113301
Neoprobe
NEOP
4.290
0.610
17%
69086
Vertex
VRTX
44.840
5.680
15% 237397
Trius
TSRX
6.240
0.670
12%
6304
Pacira
PCRX
7.100
0.650
10%
727
Exelixis
EXEL
11.820
1.060
10% 143999
Price Declines
BioCentury tracks 564 issues that report prices and volume daily. The
BioCentury 100 is a subset used to monitor price and volume trends.
BioCentury London Index
Weekly change in the combined market capitalization for 14 bioscience
stocks listed on the LSE or AIM, 12-week period. Index base =1000 on
May 10, 1996.
Feb 25
Stocks with greatest
Company
Delcath
Salix
Protalix 2
OxiGene 3
Transgene
ImmuCell
NicOx
Sanochemia
4SC
NovaBay
Questcor
% price decline (criteria as above).
Ticker
$Close
$Chg %Chg Vol(00)
DCTH
6.290 -5.010
-44% 177991
SLXP
33.490 -10.180
-23% 217517
PLX
7.630 -1.990
-21% 117942
OXGND
2.430 -0.610
-20%
3772
TNG
€12.180 -€2.670
-18%
10065
ICCC
3.070 -0.530
-15%
97
COX
€2.290 -€0.382
-14%
99666
SAC
€3.600 -€0.600
-14%
388
VSC
€3.500 -€0.460
-12%
2838
NBY
2.060 -0.270
-12%
1097
QCOR
12.610 -1.620
-11%
73856
Volume Gains
Greatest changes in volume above 5,000 shares.
Company
Ticker
Vol(00) %Chg
ProStrakan
PSK
234534 12368%
Transgene
TNG
10065 1434%
ASD
7475 1147%
Axis-Shield4
TCM
5457
868%
Tongjitang5
Abcam
ABC
15598
560%
Stentys
STNT
848
522%
MediBIC
2369
176
494%
Protalix 2
PLX
117942
395%
Salix
SLXP
217517
387%
Flamel
FLML
9659
363%
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and 18 years of industry analysis and reporting
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$Close
$Chg
132.4
23.6p
€12.18 -€2.670
316p
6.8p
4.400
0.040
350p
3p
€14.05 €2.050
¥8800 ¥600.00
7.630
-1.990
33.490 -10.180
6.440
-0.460
1 Includes volume from Toronto Stock Exchange
2 Includes volume from Tel Aviv Stock Exchange
3 Reverse split shares 1-for-20. Price and volume adjusted to reflect
split
4 Includes volume from London Stock Exchange and Oslo Bors
5 Volume figure is of ADSs (ADS = 4 shares)
BioCentury 100 Advance-Decline Trend
Week
ended
BC100
Price
level
BC100
Stocks
gaining
Jan 31
Feb 04
Feb 11
Feb 18
Feb 25
2166.44
2203.54
2210.77
2244.34
2215.82
41
70
50
63
34
BC100
Gaining
Stocks
Declining
vol. (00) declining vol. (00)
3092126
4677193
2649582
4987546
2005595
59
30
49
37
66
3717047
4512578
4327042
2544125
4106865
April 15, 2011
Millennium Broadway Hotel
& Conference Center
New York City
ORGANIZED BY
BioCentury
&
Thomson Reuters
Pharma & Investment Professionals
Register Now
The 18th Annual
FUTURE LEADERS
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Now in its 18th year, Future Leaders is firmly established as the longest
running, turf-neutral conference for investors and biopharma
professionals to conduct business. The reason is simple: BioCentury and
Thomson Reuters consistently select public and private companies that
meet the deal-making criteria of investment and pharma BD&L
professionals. The 2011 slate includes investor validated companies with
platform technologies and unpartnered assets approaching the clinic,
as well as commercially minded companies with later stage milestones.
Rodman & Renshaw
THE EXPANDING SLATE OF PRESENTING COMPANIES
with the Special Support of
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Future Leaders
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Acceleron Pharma Inc.
Achillion Pharmaceuticals Inc.
(NASDAQ:ACHN)
Alder Biopharmaceuticals Inc.
Algeta ASA (OSE:ALGETA)
Amarin Corp. plc (NASDAQ:AMRN)
ArQule Inc. (NASDAQ:ARQL)
AVI BioPharma Inc.
(NASDAQ:AVII)
BG Medicine Inc. (NASDAQ:BGMD)
Biolex Therapeutics Inc.
BioSante Pharmaceuticals Inc.
(NASDAQ:BPAX)
Cempra Pharmaceuticals Inc.
Chimerix Inc.
Complete Genomics Inc.
(NASDAQ:GNOM)
Cytori Therapeutics Inc.
(NASDAQ:CYTX; Xetra:XMPA)
Depomed Inc. (NASDAQ:DEPO)
Endoycte Inc. (NASDAQ:ECYT)
Enobia Pharma Inc.
Epigenomics AG (Xetra:ECX)
Epizyme Inc.
Euthymics Bioscience Inc.
Fate Therapeutics Inc.
Invida Group Pte. Ltd.
iPierian Inc.
Omeros Corp. (NASDAQ:OMER)
Pacira Pharmaceuticals Inc.
(NASDAQ:PCRX)
PharmAthene Inc. (NYSE-A:PIP)
Pieris AG
Progenics Pharmaceuticals Inc.
(NASDAQ:PGNX)
Repligen Corp. (NASDAQ:RGEN)
Rib-X Pharmaceuticals Inc.
S*BIO Pte. Ltd.
Threshold Pharmaceuticals Inc.
(NASDAQ:THLD)
Tolerx Inc.
Transcept Pharmaceuticals Inc.
(NASDAQ:TSPT)
Trius Therapeutics Inc.
(NASDAQ:TSRX)
Versartis Inc.
Xoma Ltd. (NASDAQ:XOMA)
Zafgen Inc.
Ziopharm Oncology Inc.
(NASDAQ:ZIOP)
WEEK OF FEBRUARY 28, 2011
BioCentury
WEEK IN REVIEW (FORMERLY BIOCENTURY PART II)
Volume 19 Number 10 Page B1 of 24
BioBusiness for the week ended February 25
COMPANY NEWS
Deals (Page B2)
Alizyme/Pharmagenix
Almirall (Madrid:ALM)/Kyorin (Tokyo:4569)
AlphaRx (OTCBB:ALRX)/Pacific Orient
(TSX-V:AAQ)
Bayer (Xetra:BAY)/Zydus Cadila (NSE:
CADILAHC; BSE:532321)
Benitec (ASX:BLT; Pink:BNIKF)/Biomics
bioMerieux (Euronext:BIM)/Ipsen (Euronext:IPN)
Calistoga/Gilead (NASDAQ:GILD)
Cell Signaling/Astellas (Tokyo:4503)
Cellerix/TiGenix (Euronext:TIG)
Clinical Data (NASDAQ:CLDA)/Forest
(NYSE:FRX)
Clinical Reference/CompanDX
Elan (NYSE:ELN)/PPD (NASDAQ:PPDI)
Eureka/Baylor
Eurofins (Euronext:EUFI)/Thermo Fisher
(NYSE:TMO)
Horizon Discovery/U of Pittsburgh
iBio (NYSE-A:IBIO)/Kentucky Bioprocessing
Isogenica/Phylogica (ASX:PYC; Xetra:PH7)
MorphoSys (Xetra:MOR)/Novartis (NYSE:
NVS; SIX:NOVN)
Naviscan/Neoprobe (NYSE:NEOP)
Nordion (TSX:NDN; NYSE:NDZ)/Best Medical
Omeros (NASDAQ:OMER)/Daiichi Sankyo
(Tokyo:4568; Osaka:4568)
Paladin (TSX:PLB)/ProStrakan (LSE:PSK)
Proacta/Yakult Honsha (Tokyo:2267; Osaka: 2267)
Pronota/Mitsubishi Chemical (Tokyo:4188)
ProStrakan (LSE:PSK)/Kyowa Hakko Kirin
(Tokyo:4151)
Quanterix/Novartis (NYSE:NVS; SIX:NOVN)
Quest (NYSE:DGX)/Thermo Fisher (NYSE:TMO)
Quintiles
Samsung Group (KSE:005930), Seoul, South Korea
Santhera (SIX:SANN)/Valeant
Stemline/U of Pittsburgh
Transgene (Euronext:TNG)/Roche (SIX:ROG;
OTCQX:RHHBY)
Univercell-Biosolutions/Kyoto U
Vical (NASDAQ:VICL)/Naval Med Res
Sales & Marketing (Page B6)
Avacta (LSE:AVCT)/Pall (NYSE:PLL)
Caliper Life Sci (NASDAQ:CALP)/Covaris
Using BioCentury Week in Review
BioCentury Week in Review (formerly
BioCentury Part II) is a comprehensive
compendium of business news for management and investors in bioscience companies. It is organized into three departments: Company News, Clinical News and
Financial News.
The index on this page lists all the
companies covered this week. The news
items in each department are organized
alphabetically by company. When more
than one company is listed, the biotech
company is shown first. Each brief is labeled with one or more applicable business categories from the following list:
ADMET; Agbio/Environmental; Antibodies; Autoimmune; Bioinformatics;
Biomanufacturing; Biopharmaceuticals;
Biosimilars; Cancer; Cardiovascular;
Chemistry; Combinatorial biology; Computational chemistry/biology; Dental; Dermatology; Diagnostic; Drug delivery; Endocrine; Finance; Functional genomics;
Gastrointestinal; Gene/Cell therapy; Generics; Genitourinary; Genomics; Hematology; Hepatic; High throughput screening; Infectious; Inflammation; Metabolic;
Microarrays; Microfluidics; Musculoskeletal; Neurology; Nutraceuticals; Ophthalmic; Other; Pharmaceuticals; Pharmacogenetics; Proteomics; Pulmonary; Renal; Supply/Service; Transplant; Veterinary
Celera (NASDAQ:CRA)/Abbott (NYSE:ABT)
Celgene (NASDAQ:CELG)/Specialised Therap
Australia
Grifols (Madrid:GRF)/Novartis (NYSE:NVS;
SIX:NOVN)
Ikaria
J&J (NYSE:JNJ)
MediGene (Xetra:MDG)/Laboratoires
Pierre Fabre
NanoString
Pharmaxis (ASX:PXS; Pink:PXSLY)
Prasco/Shire (LSE:SHP; NASDAQ:SHPGY)
PreCision Dermatology
Other News (Page B7)
Abbott (NYSE:ABT)/J&J (NYSE:JNJ)/New York U
BioCryst (NASDAQ:BCRX)/U.S. Dpt of Health
and Human Serv
Leo/Perrigo (NASDAQ:PRGO)
Microbix (TSX:MBS)
NicOx (Euronext:COX)
Novo Nordisk (CSE:NVO; NYSE:NVO)
PDL (NASDAQ:PDLI)/AstraZeneca (LSE:
AZN; NYSE:AZN)
Pfizer (NYSE:PFE)
Siga (NASDAQ:SIGA)
Stallergenes (Euronext:GENP)/Ares Life Sci
Management Tracks (Page B8)
Allon (TSX:NPC)
Amicus (NASDAQ:FOLD)
Cantargia
Fate
MorphoSys (Xetra:MOR)
Nexus Dx
Omni Bio (OTCBB:OMBP)
Pearl
QLT (TSX:QLT; NASDAQ:QLTI)
Roche (SIX:ROG; OTCQX:RHHBY)
Royal DSM (Euronext:DSM)
Swedish Orphan (SSE:SOBI)
ViiV Healthcare
CLINICAL NEWS
Regulatory (Page B9)
Abbott (NYSE:ABT)
Bristol-Myers (NYSE:BMY)
BSD Medical (NASDAQ:BSDM)
Cephalon (NASDAQ:CEPH)/InnoPharmax/
SymBio/Astellas/Eisai (Tokyo:4523; Osaka:
4523)/Mundipharma
CSL (ASX:CSL)
Delcath (NASDAQ:DCTH)
Genentech/Roche (SIX:ROG; OTCQX:RHHBY)
GlaxoSmithKline (LSE:GSK; NYSE:GSK)
HRA
Ligand (NASDAQ:LGND)/GlaxoSmithKline
(LSE:GSK; NYSE:GSK)
NicOx (Euronext:COX)
Novartis (NYSE:NVS; SIX:NOVN)
Novo Nordisk (CSE:NVO; NYSE:NVO)/
See next page
BioCentury Week in Review
FEBRUARY 28, 2011
PAGE B2 OF 24
COMPANY NEWS/Deals, Sales & Marketing, Other News, Management Tracks
DEALS
Alizyme plc, Cambridge, U.K.
Pharmagenix AG, Zurich, Switzerland
Business: Endocrine
Grant Thornton U.K. LLP, which is serving as Alizyme’s administrator after the biotech entered administration in 2009, disclosed that
Pharmagenix acquired Alizyme’s ATL-104 for £67,250 ($109,161) last
October. The mucositis candidate is a recombinant plant lectin protein
that stimulates growth of gastrointestinal epithelial cells. Further
terms were not disclosed.
Almirall S.A. (Madrid:ALM), Barcelona Spain
Kyorin Pharmaceutical Co. Ltd. (Tokyo:4569), Tokyo Japan
Business: Pulmonary
Almirall granted Kyorin Pharmaceutical exclusive rights in Japan to
develop and commercialize chronic obstructive pulmonary disease (COPD)
candidate aclidinium bromide. Almirall will receive an upfront payment and
milestones totaling up to €38 million ($52.1 million). Almirall is also
Regulatory,
from previous page
Bristol-Myers (NYSE:BMY)
Orexo (SSE:ORX)/Paladin (TSX:PLB)/
ProStrakan (LSE:PSK)/Kyowa Hakko Kirin
(Tokyo:4151)
Otsuka/Bristol-Myers (NYSE:BMY)
Pfizer (NYSE:PFE)
Protalix(NYSE-A:PLX;TelAviv:PLX)/Pfizer(NYSE:PFE)
Provepharm
R-Biopharm
Regeneron (NASDAQ:REGN)/Bayer (Xetra:BAY)
Salix (NASDAQ:SLXP)
sanofi-aventis (Euronext:SAN; NYSE:SNY)
Sunesis (NASDAQ:SNSSD)
Takeda (Tokyo:4502)
ViroPharma (NASDAQ:VPHM)
Clinical Results (Page B13)
Advancell Advanced In Vitro Cell
Amgen (NASDAQ:AMGN)/Daiichi Sankyo
(Tokyo:4568; Osaka:4568)
Aoxing (NYSE-A:AXN)/QRxPharma (ASX:
QRX; OTCQX:QRXPY)
Aprea
Axcan
Bellicum
Biogen Idec (NASDAQ:BIIB)/Elan (NYSE:ELN)
Chimerix
Dynavax (NASDAQ:DVAX)
Fate
Genzyme (NASDAQ:GENZ)
Iris (NASDAQ:IRIS)
Isis (NASDAQ:ISIS)
Medivir (SSE:MVIR B)/J&J (NYSE:JNJ)
Mitsubishi Tanabe (Tokyo:4508; Osaka:4508)/
Novartis (NYSE:NVS; SIX:NOVN)
eligible for escalating royalties. Further terms were not disclosed.
Last month, Almirall and U.S. partner Forest Laboratories Inc.
(NYSE:FRX, New York, N.Y.) said the inhalable long-acting, selective
M2 and M3 muscarinic receptor antagonist delivered using the Genuair
inhaler met the primary endpoints in the Phase III ATTAIN trial.
Regulatory submissions in the U.S. and EU for aclidinium monotherapy
are planned for mid-year (see BioCentury, Jan. 10).
AlphaRx Inc. (OTCBB:ALRX), Hong Kong, China
Pacific Orient Capital Inc. (TSX-V:AAQ), Toronto, Ontario
Business: Autoimmune
AlphaRx terminated its April 2010 letter of intent with Pacific
Orient for the acquisition of AlphaRx’s AlphaRx Canada Ltd. subsidiary
and ex-U.S., Canada and Europe rights to Indaflex. AlphaRx said the
agreement was terminated because the parties were not able to satisfy
the closing conditions of the proposed transaction. AlphaRx said it will
focus on advancing Indaflex, a topical cream formulation of indomethacin for arthritis, and GAI-122, a caspase inhibitor formulated with
AlphaRx’s nanoparticle drug delivery platform for stroke and traumatic
See next page
Neovacs (Euronext:ALNEV)
Novavax (NASDAQ:NVAX)
PolyMedix (OTCBB:PYMX)
Progenics (NASDAQ:PGNX)
TransPharma
Verona (LSE:VRP)
Vertex (NASDAQ:VRTX)
Preclinical Results (Page B18)
Harbor (OTCBB:HRBR)
Marina Biotech (NASDAQ:MRNA)
Otonomy
Clinical Status (Page B18)
Acacia
Active (SSE:ACTI)
Aestus/Astellas (Tokyo:4503)
Antares (NYSE-A:AIS)/BioSante (NASDAQ:BPAX)
BioCryst (NASDAQ:BCRX)/Green Cross/
Shionogi (Tokyo:4507; Osaka:4507)
Biomoda (OTCBB:BMOD)
Bristol-Myers (NYSE:BMY)/Eli Lilly (NYSE:
LLY)/Merck KGaA (Xetra:MRK) Dynavax
(NASDAQ:DVAX)
DynPort Vaccine
Global Health (OTCBB:GHLV)
Halozyme (NASDAQ:HALO)/Roche (SIX:
ROG; OTCQX:RHHBY)
Infinity (NASDAQ:INFI)/Mundipharma
IQ Therap
KemPharm
Medivir (SSE:MVIR B)/J&J (NYSE:JNJ)
Micell
Neovacs (Euronext:ALNEV)/NicOx (Euronext:
COX)/Grupo Ferrer
Oncolytics (TSX:ONC; NASDAQ:ONCY)
Onyx (NASDAQ:ONXX)/Bayer (Xetra:BAY)
Pharming (Euronext:PHARM)
Regeneron (NASDAQ:REGN)
Regeneron (NASDAQ:REGN)/sanofi-aventis
(Euronext:SAN; NYSE:SNY) Tarix
TcLand
Trevena
FINANCIAL NEWS
Completed Offerings (Page B22)
4SC (Xetra:VSC)
Acetylon
Biofrontera (Xetra:B8F)
Cantargia
FluGen
High Throughput Genomics
ImmunoCellular (OTCBB:IMUC)
Intercell (VSE:ICLL; OTCQX:INRLY)
Palatin (NYSE-A:PTN)
Pharmaron
SymBio
Proposed Offerings (Page B23)
Accentia (OTCQB:ABPI)
Advanced BioHealing
Cellerix
Cell Therap (NASDAQ:CTIC; Milan:CTIC)
RaQualia
Theratechnologies (TSX:TH)
TiGenix (Euronext:TIG)
Other Financial News (Page B23)
Aeterna Zentaris (TSX:AEZ; NASDAQ:AEZS)
Ardea (NASDAQ:RDEA)
Chelsea (NASDAQ:CHTP)
Genta (OTCBB:GNTAD)
Osage
Paladin (TSX:PLB)
Deals,
from previous page
brain injury, into clinical trials in China. AlphaRx granted Gaia BioPharma
Ltd. (Hong Kong, China) exclusive, worldwide rights to GAI-122.
Further terms were not disclosed.
Bayer AG (Xetra:BAY), Leverkusen, Germany
Zydus Cadila Group (NSE:CADILAHC; BSE:532321), Ahmedabad, India
Business: Pharmaceuticals
Bayer’s Bayer HealthCare unit and Zydus formed a JV, Bayer Zydus
Pharma, to market pharmaceuticals in India. Each party will hold 50% of
the JV, which will be headquartered in Mumbai, India. The JV’s portfolio
will include diabetes drug Glucobay acarbose, cardiovascular drug
Xarelto rivaroxaban, cancer drug Nexavar sorafenib, premenstrual
syndrome drug Yaz and contraceptive Yasmin from Bayer. Johnson &
Johnson (NYSE:JNJ, New Brunswick, N.J.) has U.S. rights to Xarelto
from Bayer. Bayer and Onyx Pharmaceuticals Inc. (NASDAQ:ONXX,
Emeryville, Calif.) have a worldwide co-development agreement for
Nexavar outside of Japan, where Bayer owns rights.
Benitec Ltd. (ASX:BLT; Pink:BNIKF), Melbourne, Australia
Biomics Biotechnologies Co. Ltd., Nantong, China
Business: Infectious
Following the successful identification of over 500 RNA sequences
capable of inhibiting viral replication under a 2009 deal to co-develop
and commercialize a DNA directed or vector expressed RNAi to treat
HBV infection, the companies will start an 18-month second stage
consisting of in vitro and in vivo proof-of-principle studies to optimize
a preclinical candidate. The companies will share costs, IP ownership
and commercialization rights based on agreed territories (see BioCentury,
Sept. 14, 2009).
bioMerieux S.A. (Euronext:BIM), Marcy l’Etoile, France
Ipsen Group (Euronext:IPN), Paris, France
Business: Cancer, Pharmacogenetics
bioMerieux and Ipsen partnered to co-develop hormone-dependent cancer therapeutics and companion diagnostics. Ipsen will provide
compounds, while bioMerieux will provide its diagnostic portfolio.
The companies said the partnership will focus on prostate and breast
cancers, neuroendocrine tumors and pituitary tumors. Further terms
were not disclosed.
Calistoga Pharmaceuticals Inc., Seattle, Wash.
Gilead Sciences Inc. (NASDAQ:GILD), Foster City, Calif.
Business: Cancer, Inflammation
Gilead plans to acquire cancer and inflammation company Calistoga
for $375 million in cash, plus up to $225 million in milestones. Calistoga
is developing compounds that target isoforms of phosphoinositide 3kinase (PI3K) for cancer and inflammatory diseases. Calistoga’s lead
candidate is CAL-101, a small molecule inhibitor of PI3K delta in Phase
II testing for chronic lymphocytic leukemia (CLL) and refractory indolent non-Hodgkin’s lymphoma (NHL).
JPMorgan advised Calistoga on the deal, which is expected to close
next quarter. Last month, Gilead acquired Arresto BioSciences Inc.,
whose lead product is a mAb in Phase I testing for idiopathic pulmonary
fibrosis (IPF) and advanced solid tumors (see BioCentury, Jan. 31).
Cell Signaling Technology Inc., Danvers, Mass.
Business: Cancer, Diagnostic
Astellas and Cell Signaling Technology partnered to pool their
respective IP covering the EML4-ALK oncogenic fusion protein. Astellas
FEBRUARY 28, 2011
PAGE B3 OF 24
will have rights to use the IP to develop and commercialize therapeutics,
while Cell Signaling will have rights for diagnostics. Cell Signaling said
it is developing a diagnostic using the IP for non-small cell lung cancer
(NSCLC). Astellas’ ASP3026, an inhibitor of EML4-ALK, is in Phase I
testing for cancer. Further terms were not disclosed.
Cellerix S.A., Madrid, Spain
TiGenix N.V. (Euronext:TIG), Leuven, Belgium
Business: Autoimmune, Gene/Cell therapy, Inflammation
Musculoskeletal company TiGenix will acquire Cellerix in a stock
deal that values Cellerix at €58 million ($79.8 million). TiGenix will
issue 44.8 million new TiGenix shares at €1.30. Prior to the close of
the deal, Cellerix will raise €18 million ($24.7 million) through an
offering to existing investors, while TiGenix will raise about €15
million ($20.5 million) through the sale of 15 million shares at €1 in
a rights issue. Former Cellerix investors will own 49% of the company
with TiGenix investors owning the remaining 51%.
TiGenix said the acquisition is part of its external growth strategy
and strengthens its position in the field of regenerative medicine and
cell therapy. TiGenix’s ChrondoCelect, a cell-based therapy, is approved in the EU to treat cartilage defects of the femoral condoyle of
the knee. The initial focus of the combined group will be damaged and
arthritic joints with future expansion planned for other inflammatory
and autoimmune disorders. Cellerix’s Cx601, which comprises expanded stem cells obtained from allogeneic adipose tissue (eASCs), has
completed Phase IIa testing in complex perianal fistulas in Crohn’s
disease (CD) patients and has Orphan Drug designation in the EU for
anal fistula. The deal, which is expected to close in June, is subject to
shareholder approval from both companies. TiGenix and Cellerix have
scheduled shareholder meetings in April and March, respectively.
Kempen & Co. advised TiGenix, while Piper Jaffray advised Cellerix.
Kempen and KBC Securities are acting as joint bookrunners for the
rights issue (see BioCentury, Feb. 2).
Clinical Data Inc. (NASDAQ:CLDA), Newton, Mass.
Forest Laboratories Inc. (NYSE:FRX), New York, N.Y.
Business: Neurology
Forest will acquire Clinical Data for $30 per share in cash, plus a
contingent value right worth up to $6 based on sales milestones of
Clinical Data’s depression drug Viibryd vilazodone. The upfront portion represents about $928.6 million, based on 31 million shares
outstanding on Feb. 8, and is a 67% premium to Clinical Data’s close of
$15.03 on Jan. 21, the last trading day before FDA approved Viibryd. At
that time, Clinical Data said it was considering a potential takeover of
the company or a deal to partner Viibryd. The boards of both companies
have approved the deal, which is expected to close next quarter. Forest
said Viibryd will enhance its depression portfolio, which includes
Celexa citalopram and Lexapro escitalopram.
Forest expects to launch the mixed selective serotonin reuptake
inhibitor (SSRI) and partial serotonin (5-HT1A) next half. The CVR will
pay $1 if U.S. net sales of Viibryd over four quarters reach or exceed
$800 million within the first five years. It will pay $2 and $3 if sales reach
or exceed $1.1 billion within the first six years and $1.5 billion and
seven years, respectively. Morgan Stanley advised Forest, while JPMorgan
advised Clinical Data.
Lexapro is an allosteric SSRI and Celexa is an orally disintegrating
tablet (ODT) formulation of citalopram hydrobromide serotonin (5HT) reuptake inhibitor.
Clinical Reference Laboratory Inc., Lenexa, Kan.
CompanDX Ltd., Nottingham, U.K.
Business: Diagnostic, Pharmacogenetics
See next page
Deals,
from previous page
The companies will partner to develop biomarker panels and
companion diagnostic tests. Under the deal, CompanDX will continue
to develop its Distiller bioinformatics platform, which aids in the
selection of candidate biomarkers, the generation of biomarker signatures and subsequent functional analysis of these signatures. CompanDX
will derive the biomarker signatures and Clinical Reference’s CLIAcertified labs will develop tests. Ownership of IP will be determined
on a case by case basis. Financial terms were not disclosed.
Elan Corp. plc (NYSE:ELN), Dublin, Ireland
PPD Inc. (NASDAQ:PPDI), Wilmington, N.C.
Business: Supply/Service
Elan and PPD will collaborate to advance Elan’s various therapeutic
programs through clinical testing. The deal makes PPD the preferred
provider of CRO services for the biotech and will allow Elan to leverage
PPD’s strengths in data management, biostatistics, and regulatory,
clinical and medical monitoring to advance compounds in a “parallel
manner.” Elan will retain its focus on in-house discovery and R&D of
therapeutics as well as ownership of compounds, and is responsible for
all developmental decisions. Financial terms were not disclosed.
Eureka Genomics Corp., Hercules, Calif.
Baylor Research Institute, Baylor, Texas
Business: Cancer
The parties will collaborate to confirm the role of the JC virus (JCV)
in colorectal cancer and to identify other possible microbial or genetic
factors of the disease. The institute will provide clinical resources and
IP regarding JCV as a potential causative agent of colorectal cancer.
Eureka will use its bioinformatics technology to screen sequence data
to look for the presence of human and/or non-human sequences
associated with colorectal cancer samples that are absent in other
samples. The parties will jointly own any IP relating to the biology or
etiology of cancer arising from the collaboration, and will share
revenues from the commercialization of any potential diagnostics and
treatments that arise out of the deal.
Eurofins Scientific S.A. (Euronext:EUFI), Kraainem, Belgium
Thermo Fisher Scientific Inc. (NYSE:TMO), Waltham, Mass.
Thermo Fisher plans to sell its contract testing unit, Lancaster
Laboratories Inc., to Eurofins for $200 million. Lancaster had about
$115 million in revenues last year. Eurofins said the unit, based in
Lancaster, Pa., will significantly enlarge its North American presence.
Thermo Fisher, which had $10.8 billion in revenues last year, said the
unit is not part of the company’s core business. The deal is expected
to close next quarter.
Horizon Discovery Ltd., Cambridge, U.K.
University of Pittsburgh, Pittsburg, Pa.
Business: Cancer, Gene/Cell therapy
The university granted Horizon exclusive, worldwide rights to isogenic
cell models, including a model for miRNA21, which the company said is
“implicated in a wide range of cancers.” The cell lines will be added to
Horizon’s X-MAN cell lines. The university will receive an upfront
payment and is eligible for royalties. Further terms were not disclosed.
iBio Inc. (NYSE-A:IBIO), Newark, Del.
Kentucky Bioprocessing LLC, Owensboro, Ky.
Business: Metabolic
iBio acquired rights from Kentucky Bioprocessing to plant-pro-
FEBRUARY 28, 2011
PAGE B4 OF 24
duced human alpha galactosidase A. iBio will use its iBioLaunch plantbased vaccine and therapeutic protein manufacturing platform to further develop the enzyme to treat Fabry’s disease. iBio said it will
collaborate with the not-for-profit Fraunhofer USA Center for Molecular Biotechnology (Newark, Del.) for development of the enzyme,
which is in preclinical testing. Kentucky Bioprocessing will be responsible for manufacturing the enzyme. Further terms were not disclosed.
Isogenica Ltd., Little Chesterford, U.K.
Phylogica Ltd. (ASX:PYC; Xetra:PH7), Subiaco, Australia
Business: Inflammation
The companies successfully completed a proof of concept (POC)
project under a 2010 deal demonstrating the compatibility of Isogenica’s
CIS display technology with Phylogica’s Phylomer drug discovery platform for peptide engineering and drug discovery. Under the deal,
Isogenica is using its CIS display technology to optimize three undisclosed peptides from Phylogica targeting CD40 ligand (CD154) for
inflammatory diseases (see BioCentury, Feb. 8, 2010). Further details
were not disclosed.
MorphoSys AG (Xetra:MOR), Martinsried, Germany
Business: Antibodies
MorphoSys received an undisclosed double-digit million Euro milestone payment from Novartis under a 2007 deal that gave Novartis
preferred exclusive access to MorphoSys’ HuCAL antibody technology.
The payment was triggered by the installation of the HuCAL technology
at a Novartis R&D site in Basel, Switzerland. Last October, MorphoSys
exercised its second option to participate in development of a second
antibody under the deal to treat an inflammatory disease. MorphoSys
said five antibody programs under the deal are currently in clinical
testing, including lead compound BHQ880, an antibody against dickkopf
homolog 1 (DKK1) in Phase II testing to treat multiple myeloma. The
other programs are evaluating antibodies for ophthalmic and musculoskeletal diseases, with three programs in Phase I and one program in
Phase II testing (see BioCentury, Oct. 25, 2010).
Naviscan Inc., San Diego, Calif.
Neoprobe Corp. (NYSE:NEOP), Dublin, Ohio
Business: Diagnostic
Naviscan granted Neoprobe an exclusive, worldwide license to its
gamma imaging technology for surgical applications in cancer. Neoprobe
said the technology could lead to new indications for its Lymphoseek
and RIGScan CR imaging products. Lymphoseek, a Tc99m-labeled
radioactive tracing agent, is in Phase III testing for intraoperative lymph
node mapping in patients with melanoma or breast cancer. Neoprobe
has a pre-IND meeting with FDA to discuss a BLA for its RIGScan CR
technology this quarter. RIGScan is an iodine-labeled mAb fragment
targeting TAG72 cancer antigen. Financial terms were not disclosed.
Nordion Inc. (TSX:NDN; NYSE:NDZ), Ottawa, Ontario
Best Medical International Inc., Springfield, Va.
Business: Supply/Service, Cancer, Diagnostic
Nordion will divest its MDS Nordion S.A. operation in Fleurus,
Belgium, including Nordion’s radiopharmaceutical business, to Best Medical in a stock deal. The parties signed a letter of intent last December. Best
Medical will acquire all of Nordion’s Belgian operations except its
TheraSphere business, which consists of yttrium-90 glass microspheres
used for localized radioembolization therapy. The deal is expected to
close within a few months. Nordion said it will resume its plans to
restructure operations at the Fleurus site after the divestiture. Further
terms were not disclosed (see BioCentury, Dec. 13, 2010).
See next page
Deals,
from previous page
Omeros Corp. (NASDAQ:OMER), Seattle, Wash.
Daiichi Sankyo Co. Ltd. (Tokyo:4568; Osaka:4568), Tokyo, Japan
Business: Neurology
The companies added addiction and compulsive disorders to a 2010
deal under which Daiichi Sankyo’s Asubio Pharma Co. Ltd. subsidiary
granted Omeros an exclusive, worldwide license to undisclosed preclinical compounds for use in Omeros’ phosphodiesterase-7 (PDE-7)
program to treat movement disorders. Daiichi Sankyo is now eligible
for up to $30.2 million in milestones from Omeros, an increase from
the $23.5 million it was eligible for under the original deal. Financial
terms were not disclosed (see BioCentury, March 15, 2010).
Paladin Labs Inc. (TSX:PLB), Montreal, Quebec
ProStrakan Group plc (LSE:PSK), Galashiels, U.K.
Business: Neurology, Gastrointestinal, Endocrine
The companies amended a 2008 deal that was expanded last year
after it was announced that Kyowa Hakko Kirin Co. Ltd. (Tokyo:4151,
Tokyo, Japan) is acquiring ProStrakan for 130p per share, or about £292
million ($474 million) in cash. Paladin agreed to accept repayment of a
secured debt facility of £50 million ($81.2 million) from ProStrakan.
Paladin will also receive a payment equivalent to the balance of interest
payable for the first year plus a £2 million ($3.2 million) break free.
Under the expansion, Paladin received exclusive rights to market
ProStrakan’s products in Canada, Latin America, Sub-Saharan Africa and
Israel. Paladin also acquired the secured debt facility and rights to
license new products acquired or licensed by ProStrakan for the
territories. Paladin will retain the rights to the products in Canada and
select emerging markets from the original deal (see BioCentury, Jan. 5,
2009 & Dec. 20, 2010).
Proacta Inc., La Jolla, Calif.
Yakult Honsha Co. Ltd. (Tokyo:2267; Osaka:2267), Tokyo, Japan
Business: Cancer
Proacta granted Yakult Honsha exclusive rights to cancer candidate
PR509 in Japan. The partners will complete preclinical and Phase I trials
of the compound in the U.S. after which Yakult can exercise the option
to further clinical development and commercialization in Japan. The
hypoxia activated irreversible pan-ebrB inhibitor is currently in preclinical testing to treat erlotinib-resistant non-small cell lung cancer
(NSCLC). Financial details were not disclosed.
Tarceva erlotinib is approved for first-line maintenance and secondline treatment of advanced or metastatic NSCLC and to treat pancreatic
cancer. The small molecule inhibitor of EGRF tyrosine kinase activity
is marketed in the U.S. by OSI Pharmaceuticals Inc., now part of Astellas
Pharma Inc. (Tokyo:4503, Tokyo, Japan), and Genentech Inc., a unit of
Roche (SIX:ROG; OTCQX:RHHBY, Basel, Switzerland), and by Roche
elsewhere.
Pronota N.V., Zwijnaarde, Belgium
Mitsubishi Chemical Holdings Corp. (Tokyo:4188), Tokyo, Japan
Pronota and Mitsubishi Chemical Holdings’ Molecuence Corp.
subsidiary partnered to discover and validate protein biomarkers to
diagnose stroke. Pronota will use its MASStermind protein biomarker
discovery platform and MASSterclass protein biomarker verification
tool. Further terms were not disclosed.
Kyowa Hakko Kirin Co. Ltd. (Tokyo:4151), Tokyo, Japan
Business: Neurology
FEBRUARY 28, 2011
PAGE B5 OF 24
Kyowa Hakko Kirin will acquire ProStrakan for 130p per share, or
about £292 million ($474 million) in cash. The price is a 20% premium
to ProStrakan’s close of 108.90p on Feb. 18, before the deal was
announced. Kyowa said the acquisition will provide an established EU
and U.S. sales force. It also will gain ProStrakan’s specialty pharmaceutical products, including pain drug Abstral fentanyl. ProStrakan, which
has rights to the sublingual mucoadhesive fentanyl in North America and
Europe from Orexo AB (SSE:ORX, Uppsala, Sweden), plans to launch
the product in the U.S. this quarter. In January, ProStrakan said it
expected 2010 revenue of £100 million ($154.9 million).
The boards of both companies have approved the offer, which is
subject to approval by ProStrakan shareholders at a meeting in April.
The deal is expected to close by early June. BofA Merrill Lynch is advising
Kyowa Hakko Kirin, while JPMorgan Cazenove and Numis are advising
ProStrakan.
Quanterix Corp., Cambridge, Mass.
Novartis AG (NYSE:NVS; SIX:NOVN), Basel Switzerland
Quanterix and Novartis’ Novartis Vaccines and Diagnostics Inc.
subsidiary will evaluate the potential use of Quanterix’s single molecule array (SiMoA) technology for developing diagnostics. The evaluation will focus on an undisclosed neuron-specific protein target.
Quest Diagnostics Inc. (NYSE:DGX), Madison, N.J.
Thermo Fisher Scientific Inc. (NYSE:TMO), Waltham, Mass.
Thermo Fisher plans to sell its Athena Diagnostics Inc. unit to Quest
for $740 million. Athena, which had about $110 million in revenues last
year, markets diagnostics for neurological and developmental disorders.
Quest said the acquisition would complement its existing diagnostics in
cancer, infectious diseases and cardiovascular diseases. Thermo Fisher,
which had $10.8 billion in revenues last year, said the unit is not part of
the company’s core business. The deal is expected to close next quarter.
In 2002, Elan Corp. plc (NYSE:ELN, Dublin, Ireland) sold its 80% stake in
Athena to investment group Behrman Capital (New York, N.Y.) for $82
million (see BioCentury, Nov. 25, 2002).
Quintiles Transnational Corp., Research Triangle Park, N.C.
Samsung Group, Seoul, South Korea
Business: Biosimilars
Samsung and Quintiles will form a 90/10 JV to manufacture biosimilars
in South Korea. Quintiles will contribute about $30 million to the JV,
with Samsung contributing the remaining $236 million. The JV plans to
begin building a contract manufacturing facility in May. The facility is
expected to be operational by April 2013. Samsung said this is the first
move under a plan announced last May to invest about $1.8 billion in
biopharmaceuticals.
Santhera Pharmaceuticals Holding AG (SIX:SANN), Liestal, Switzerland
Valeant Pharmaceuticals International Inc. (NYSE:VRX; TSX:VRX),
Mississauga, Ontario
Business: Neurology
Santhera announced the completion of Valeant’s return of U.S. and
Canadian rights to fipamezole (JP-1730). Valeant gained rights to the
program through its merger with Biovail Corp. last year, but decided
not to continue the project after a review of the merged company’s
pipelines, according to Santhera (see BioCentury, Nov. 1, 2010).
Santhera said it will seek to license U.S. and Canadian rights to
fipamezole to a new partner this year. Santhera plans to start Phase III
See next page
Deals,
from previous page
testing for the adrenergic receptor alpha 2 (ADRA2) antagonist to treat
dyskinesia in patients with Parkinson’s disease (PD). Fipamezole is
partnered with Ipsen Group (Euronext:IPN, Paris, France) outside the
U.S., Canada and Japan, where. Santhera retains rights.
Stemline Therapeutics Inc., New York, N.Y.
University of Pittsburgh, Pittsburgh, Pa.
Business: Cancer
The university granted Stemline exclusive, worldwide rights to SL701, a cancer vaccine targeting tumor bulk and cancer stem cells. The
vaccine is in Phase I/II testing to treat glioblastoma multiforme (GBM).
The university will receive an upfront payment and is eligible for
milestones and royalties. Further terms were not disclosed.
Transgene S.A. (Euronext:TNG), Illkirch, France
Roche terminated the partners’ 2007 deal and returned rights to
TG4001 (RG3484) for HPV-mediated diseases. Roche said the decision
was strategic and not “data-driven.” The vaccinia virus vector encoding
HPV type 16 E6 and E7 antigens and an IL-2 coding sequence is in a Phase
IIb trial to treat high grade cervical intraepithelial neoplasia (CIN)
lesions (CIN2/3) caused by HPV infection, with data expected by year
end or early next year. Transgene said that if data from the ongoing trial
are positive, the company plans to begin Phase III testing in late 2012
or early 2013 and look for a co-development partner (see BioCentury,
April 16, 2007).
Univercell-Biosolutions S.A.S., Toulouse, France
Kyoto University, Kyoto, Japan
Business: Gene/Cell therapy
Univercell received a non-exclusive, worldwide license to an
induced pluripotent stem cell (iPSC) patent portfolio from the
university’s technology transfer arm, iPS Academia Japan Inc. Univercell
plans to use the technology to provide cardiac cells without the use of
embryonic stem cells to the pharma industry to aid drug discovery and
to reduce drug failure rates in clinical trials. iPS is eligible for royalties.
Vical Inc. (NASDAQ:VICL), San Diego, Calif.
Naval Medical Research Center, Silver Spring, Md.
The biotech and research center will establish systems and procedures to develop Vical’s DNA delivery technology for the rapid
development and production of vaccines against emerging infectious
diseases for military personnel. Financial terms were not disclosed.
The collaboration is an extension of a 2010 deal under which the U.S.
Department of Defense’s Defense Threat Reduction Agency (DTRA)
and NMRC provided funding to Vical to support development of its
Vaxfectin-formulated DNA vaccine to prevent swine influenza A (H1N1).
The vaccine is expected to complete Phase I testing this quarter.
FEBRUARY 28, 2011
PAGE B6 OF 24
early analysis of compounds to identify the best candidates for development and define the optimal processing conditions. The companies
also said they plan to market additional instruments developed by
Avacta to help companies bring drugs to market. Further terms were
not disclosed.
Caliper Life Sciences Inc. (NASDAQ:CALP), Hopkinton, Mass.
Covaris Inc., Woburn, Mass.
Business: Supply/Service, Microfluidics
The companies will co-promote Covaris’ acoustic DNA shearing
platforms and Caliper’s sequencing and microfluidics technologies to
develop automated workflows for next generation sequencing experiments. Further terms were not disclosed.
Celera Corp. (NASDAQ:CRA), Alameda, Calif.
Abbott Laboratories (NYSE:ABT), Abbott Park Ill.
Abbott launched Celera’s KIF6 Genotyping Assay in Europe as an
aid in determining the risk of coronary heart disease (CHD). Abbott
will market the test to run on its m2000 lab automation system. The
real-time in vitro PCR test detects variants in the 719Arg kinesin-like
protein 6 (KIF6) gene and has CE Mark approval in the EU.
Celgene Corp. (NASDAQ:CELG), Summit, N.J.
Specialised Therapeutics Australia Pty. Ltd., Victoria, Australia
Business: Cancer
Specialised Therapeutics launched Abraxane nab-paclitaxel in New
Zealand to treat metastatic breast cancer. Specialised Therapeutics
received exclusive rights to the albumin stabilized nanoparticle formulation of paclitaxel in New Zealand in 2008. Celgene gained rights to
Abraxane through its 2010 acquisition of Abraxis BioScience Inc. (see
BioCentury, July 5, 2010).
Grifols S.A. (Madrid:GRF), Barcelona, Spain
Business: Diagnostic, Hematology
Novartis’ Novartis Diagnostics Inc. subsidiary will commercialize select Grifols’ diagnostic products in the U.S. The deal covers
semi-automated pre-transfusion diagnostic products from Grifols
subsidiaries, immunohematology instruments, assays and other
products. Novartis will also commercialize Bloodchip molecular
biology products for genotyping blood donors. Grifols has exclusive, worldwide rights to distribute the Bloodchip product line
under a 2010 deal with Progenika Biopharma S.A. (Derio, Spain).
Financial terms were not disclosed.
SALES & MARKETING
Ikaria Inc., Clinton, N.J.
Business: Pulmonary
Ikaria’s Ikaria Canada Inc. subsidiary launched its INOMAX DSIR
drug-delivery system for the administration of INOMAX nitric oxide in
Canada. Ikaria markets INOMAX to treat term and near-term infants
with hypoxic respiratory failure. The system is the next generation of
Ikaria’s INOMAX DS drug-delivery system, which was recalled last year
due to the potential failure of a pressure switch that may affect the
administration of INOMAX. Ikaria plans to launch INOMAX DSIR in
Australia and Canada this half (see BioCentury, Aug. 16, 2010).
Avacta Group plc (LSE:AVCT), Heslington, U.K.
Pall Corp. (NYSE:PLL), Port Washington, N.Y.
Business: ADMET
Avacta and Pall will co-promote Avacta’s Optim 1000 ultra-low
volume biopharmaceutical analysis tool in North America. Optim 1000
was developed to accelerate the speed of drug development through
Johnson & Johnson’s Janssen Biologics B.V. unit recalled 395
Simponi golimumab injector devices, including 230 in Germany and 165
in U.S., due to a potential defect in the injection pens that could result
See next page
Sales & Marketing,
from previous page
in an insufficient dose of the drug. Janssen said it will be able to resupply
the pens to the European market by the end of February, but not all
countries in Europe will have regular supplies until May. J&J’s Centocor
Ortho Biotech Inc. unit plans to resume distribution in the U.S. at the
end of March. The human mAb against tumor necrosis factor (TNF)
alpha is approved to treat moderate to severe rheumatoid arthritis
(RA), psoriatic arthritis and ankylosing spondylitis. J&J manufactures
the pens in Europe and markets the product in the U.S., while Merck
& Co. Inc. (NYSE:MRK, Whitehouse Station, N.J), in a partnership with
J&J, markets the devices in Europe.
MediGene AG (Xetra:MDG), Martinsried, Germany
Laboratoires Pierre Fabre S.A., Castres, France
MediGene granted Pierre Fabre’s Pierre Fabre Medicament exclusive marketing rights to Veregen sinecatechins to treat genital warts in
Mexico, Central America, Venezuela and Columbia. MediGene will
receive an upfront payment and is eligible for milestones. Pierre Fabre
will be responsible for approval in the territories. Further terms were
not disclosed. The product is already approved in Germany and Austria.
The topical formulation of polyphenols extracted from green tea leaves
is approved in the U.S. to treat external genital warts and perianal warts
in immunocompetent patients ≥18 years of age. MediGene has exclusive, worldwide rights to Veregen for genital warts and hyperplasia
caused by papilloma viruses from Epitome Pharmaceuticals Ltd. (Halifax,
Nova Scotia), which licensed rights from Mitsui & Co. Ltd. (Tokyo:8031,
Tokyo, Japan).
NanoString Technologies Inc., Seattle, Wash.
Business: Genomics
NanoString launched its nCounter Human Karyotype Panel in the
U.S. for digital counting of human chromosomes and detection of
aneuploidy. The kit runs on the company’s nCounter Analysis System,
an automated system for digital gene expression analysis. The nCounter
Analysis System and Human Karyotype Panel are available for research
use only.
Pharmaxis Ltd. (ASX:PXS; Pink:PXSLY), Frenchs Forest, Australia
Pharmaxis launched its Aridol mannitol Bronchial Challenge Test
Kit in the U.S. to assess bronchial hyperresponsiveness in patients six
years of age and older who do not have clinically apparent asthma. The
indirect bronchial challenge test comprising dry mannitol powder and
inhaler is approved in Australia, the EU, Switzerland and South Korea
(see BioCentury, Oct. 11, 2010).
Prasco LLC, Mason, Ohio
Shire plc (LSE:SHP; NASDAQ:SHPGY), Dublin, Ireland
Prasco will market an authorized generic formulation of Pentasa
mesalamine capsules to treat ulcerative colitis in the U.S. in a deal with
Shire’s Shire US Manufacturing Inc. unit. Prasco is prepared to launch
the generic mesalamine at Shire’s request once FDA approves an ANDA
for mesalamine. Pentasa had U.S. sales of $235.9 million in 2010.
Financial terms were not disclosed.
Last year, FDA denied Shire’s request in a Citizen’s Petition that
generic formulations of the controlled-release mesalamine be required
to conduct studies with clinical endpoints in order to demonstrate
bioequivalence. Shire acquired Pentasa under its 1999 acquisition of
Roberts Pharmaceutical Corp. (see BioCentury, July 26, 1999 & Aug. 30, 2010).
FEBRUARY 28, 2011
PAGE B7 OF 24
PreCision Dermatology, Cumberland, R.I.
Business: Dermatology
PreCision’s Onset Dermatologics company launched its
HylatopicPlus-Aurstat Kit in the U.S. The kit contains HylatopicPlus
Emollient Foam to manage and relieve burning, itching and pain of skin
dermatoses, and Aurstat Skin and Wound HydroGel to relieve skin
irritation, minor abrasions and lacerations. The wholesale acquisition
price of the kit is $200 for a one month supply.
OTHER NEWS
Abbott Laboratories (NYSE:ABT), Abbott Park, Ill.
New York University, New York, N.Y.
The U.S. Court of Appeals for the Federal Circuit overturned
a 2009 jury verdict that awarded $1.7 billion to Johnson & Johnson’s
Centocor Ortho Biotech Inc. unit and the university after finding
Abbott liable for patent infringement. A three-judge panel at the
CAFC said in its decision that patents co-owned by the university
and Ortho Biotech covering the use of antibodies against tumor
necrosis factor (TNF) alpha are invalid and therefore not infringed
by Abbott’s autoimmune drug Humira adalimumab. Centocor said
in a statement it is considering whether to request a reconsideration of the appeal by the three-judge panel or by the full CAFC.
Humira, a mAb against TNF alpha, had 2010 sales of $6.5 billion (see
BioCryst Pharmaceuticals Inc. (NASDAQ:BCRX), Birmingham, Ala.
U.S. Department of Health and Human Services, Washington, D.C.
BioCryst said HHS awarded the company a two-year $55 million
contract extension through YE13 to fund the completion of Phase III
development of influenza candidate peramivir. BioCryst, which is
developing peramivir under a contract with HHS, has now received a
total of $234.8 million from the agency to fund Phase III development
and an NDA submission for the injectable formulation of a viral
neuraminidase inhibitor. The biotech was originally awarded a fouryear $102.6 million contract in January 2007 and received a one-year
$77.2 million contract extension in September 2009. Late last month,
BioCryst said it was seeking permission and additional funding from
HHS to expand an ongoing Phase III trial (BCX1812-301) of peramivir
(see BioCentury, Sept. 28, 2009 & Jan. 17, 2011).
Peramivir is approved as Rapiacta in Japan. Shionogi & Co. Ltd.
(Tokyo:4507; Osaka:4507, Osaka, Japan) has Japanese and Taiwanese
rights to peramivir from BioCryst, while Green Cross Corp. (YonginSi, South Korea) has South Korean rights.
Leo Pharma A/S, Ballerup, Denmark
Perrigo Co. (NASDAQ:PRGO), Allegan, Mich.
Leo filed suit in the U.S. District Court for the Southern District of
New York alleging that Perrigo infringed U.S. patent No. 6,753,013
covering Leo’s psoriasis drug Taclonex calcipotriene/betamethasone
dipropionate. Perrigo submitted an ANDA to FDA for a generic version
of Taclonex last year. The ANDA contains a Paragraph IV notification
that the ‘013 patent is invalid, unenforceable and/or will not be infringed
by the approval or sale of Perrigo’s generic. Leo is seeking to prevent
the approval and sale of Perrigo’s generic before the ‘013 patent expires
on Jan. 27, 2020.
Healthcare information company Wolters Kluwer Health said sales
of Taclonex were $135 million for the 12-month period ending NovemSee next page
Other News,
from previous page
ber 2010. Taclonex is a combination of topical calcipotriene plus
betamethasone dipropionate.
Microbix Biosystems Inc. (TSX:MBS), Toronto, Ontario
Microbix formed a subsidiary in China called Crucible International
Biotechnologies Corp. to commercialize Microbix’s VIRUSMAX technology. Microbix transferred to the subsidiary its influenza vaccine
assets, including an exclusive, worldwide license to the technology,
which increases the yield of viral vaccines manufactured in chicken eggs.
Crucible will also receive Microbix’s 50% ownership in its Chinese JV
with China’s Hunan Provincial Government. The JV was formed to
produce influenza vaccine using the VIRUSMAS technology. Microbix
will own about 80% of the subsidiary (see BioCentury, June 30, 2008).
NicOx S.A. (Euronext:COX), Sophia-Antipolis, France
Business: Autoimmune, Cardiovascular, Endocrine
NicOx disclosed in its 2010 earnings that it reduced headcount by
50% at its headquarters in France and by 35% at its Bresso, Italy,
subsidiary. The reduction, which represents a decrease in total
headcount by 65 (51%) to 63, is part of the company’s global restructuring announced last year under which the company closed its U.S.
headquarters in Warren, N.J., last August. The restructuring follows
the receipt of a complete response letter from FDA in July for an NDA
for naproxcinod, a cyclooxygenase (COX)-inhibiting nitric oxide donator (CINOD) that releases naproxen and nitric oxide, to treat signs and
symptoms of osteoarthritis (OA). The company said the restructuring
will reduce its FY11 cash burn by about two thirds from 2010 levels. At
Dec. 31, the company had €107.3 million ($143.2 million) in cash and
a 12-month operating loss of €44 million ($58.7 million) (see BioCentury,
Aug. 9, 2010).
Novo Nordisk A/S (CSE:NVO; NYSE:NVO), Bagsvaerd, Denmark
Business: Endocrine
Novo Nordisk received a subpoena from the U.S. Attorney’s Office
for the District of Massachusetts requesting documents related to
potential criminal offenses by the company’s marketing practices of
three diabetes drugs: NovoLog insulin aspart; Levemir insulin detemir;
and Victoza liraglutide. Novo Nordisk said it intends to cooperate with
the investigation. NovoLog and Levemir are rapid- and long-acting
insulin analogs, respectively. Victoza is a long-acting analog of glucagonlike peptide-1 (GLP-1). The company reported 2010 sales of DKK6.9
billion ($1.2 billion) and DKK2.3 billion ($414.5 million) for Levemir
and Victoza, respectively.
FEBRUARY 28, 2011
PAGE B8 OF 24
ever, the court did rule that MedImmune is not entitled to recoup
royalties on sales of Synagis that MedImmune paid to PDL based on
European patent rights that were ultimately revoked.
In 1998, PDL granted the AstraZeneca subsidiary a non-exclusive
license to IP covering humanized antibodies. Synagis, which is a humanized
mAb, had worldwide sales of $1 billion in 2010 (see BioCentury, Jan. 17).
The U.S. Supreme Court ruled 6-2 in Bruesewitz v. Wyeth that the
National Childhood Vaccine Injury Act of 1986 “preempts all designdefect claims against vaccine manufacturers brought by plaintiffs seeking
compensation for injury or death caused by a vaccine’s side effects.” The
ruling upholds a 2009 decision by the U.S. Court of Appeals for the Third
Circuit. The Bruesewitzs originally filed a petition under the vaccine act
in April 1995, alleging that their daughter’s residual seizure disorder
and developmental impairment was caused by Wyeth’s Tri Immunol, a
diphtheria-pertussis-tetanus (DTP) vaccine. Tri Immunol was removed
from the market in 1998 favor of a vaccine with an acellular pertussis
component. Wyeth was acquired by Pfizer in 2009.
Siga Technologies Inc. (NASDAQ:SIGA), New York, N.Y.
Siga said that the HHS’s Biomedical Advanced Research and Development Authority (BARDA) advised that it is issuing a request for
proposal for 1.7 million courses of a smallpox antiviral, with an option
to acquire 12 million more. Siga said it plans to respond to the request.
Responses are due Feb. 28. Earlier this month, Siga announced that the
U.S. Small Business Administration Office of Hearings and Appeals
affirmed a November ruling that Siga was not a small business and
therefore would not be eligible for an HHS small business contract for
a smallpox antiviral that would have been worth up to $2.8 billion. Siga’s
antiviral, ST-246, is in Phase II testing (see BioCentury, Feb. 21).
Stallergenes S.A. (Euronext:GENP), Antony, France
Ares Life Sciences, Geneva, Switzerland
Investment firm Ares re-opened its mandated offer in compliance
with European law for the remaining stake of Stallergenes it does not
own for €59 per share, or €424.5 million ($581.5 million). The price
is a premium to Stallergenes’ close of €58.79 on Jan. 7, the day before
the tender was announced. As of Feb. 21, Ares had increased its stake
in Stallergenes to about 68%. Ares acquired a 45.86% stake in Stallergenes
from investment firm Wendel (Paris, France) for €358.8 million
($491.5 million), or €59 per share in November. The tender offer will
close on March 11 (see BioCentury, Jan. 17).
MANAGEMENT TRACKS
PDL BioPharma Inc. (NASDAQ:PDLI), Incline Village, Nev.
AstraZeneca plc (LSE:AZN; NYSE:AZN), London, U.K.
PDL paid $92.5 million to AstraZeneca’s MedImmune LLC subsidiary to settle a patent dispute related to MedImmune’s respiratory
syncytial virus drug Synagis palivizumab. As part of the settlement,
MedImmune will not make any more payments to PDL for past or future
sales of Synagis, and has agreed not to challenge PDL’s patents.
In January, the U.S. District Court for the Northern District of
California ruled that Synagis did not infringe a PDL patent. The court said
MedImmune did not breach its obligations under a deal with PDL by
failing to pay royalties on sales of Synagis by MedImmune’s ex-U.S.
distributor, Abbott Laboratories (NYSE:ABT, Abbott Park, Ill.). How-
BioCentury Extra: Online every business day.
Boards of Directors
Royal DSM N.V. (Euronext:DSM), Heerlen, the Netherlands
Business: Pharmaceuticals, Biomanufacturing, Supply/Service
Appointed: Rob Routs as chairman, effective after an April 28 general
meeting, formerly a director at Royal Dutch Shell plc; he succeeds Cor
Herkstroter
ViiV Healthcare, Brentford, U.K.
Appointed: David Redfern, chief strategy officer at GlaxoSmithKline
plc, as chairman, effective April 1; he replaces Julian Heslop, who is
retiring; ViiV is a HIV-focused JV between GSK and Pfizer Inc.
See next page
FEBRUARY 28, 2011
PAGE B9 OF 24
CLINICAL NEWS
Clinical activities and selected announcements for the week ended February 25.
REGULATORY
Abbott Laboratories (NYSE:ABT), Abbott Park, Ill.
Product: Humira adalimumab
EMA’s CHMP issued a positive opinion to extend the label of
Humira adalimumab to include the treatment of juvenile idiopathic
arthritis in patients aged 4-12 years. The human mAb against tumor
necrosis factor (TNF) alpha is already approved in the EU to treat
polyarticular juvenile idiopathic arthritis in patients aged 13-17 years,
ankylosing spondylitis, moderate to severe active rheumatoid arthritis
(RA), active and progressive psoriatic arthritis, severe active Crohn’s
disease (CD) and psoriasis in adults.
Product: Zerit stavudine
EMA’s CHMP recommended renewal of marketing authorization
for Bristol-Myers’ HIV drug Zerit stavudine but with restrictions due
to severe side effects. The restrictions include that the product should
be used for as short a time as possible and only when there are no
appropriate alternatives. The agency noted that the side effects, which
include lipoatrophy, lactic acidosis and peripheral neuropathy, were
more commonly seen with Zerit than with other nucleoside analog
reverse transcriptase inhibitors (NRTIs).
BSD Medical Corp. (NASDAQ:BSDM), Salt Lake City, Utah
Product: BSD-2000 Hyperthermia System
Business: Cancer
The National Comprehensive Cancer Network (NCCN) updated
Management Tracks,
from previous page
its clinical practice guidelines in oncology to include hyperthermia and
chemotherapy as a recommended treatment for high-risk soft tissue
sarcoma (STS) based on data from BSD’s Phase III trial of its BSD-2000
Hyperthermia System (see BioCentury, May 10, 2010). A Humanitarian
Device Exemption (HDE) application is under FDA review for the
hyperthermia system using focused electromagnetic energy radiated at
about 100 MHz (radio frequency). The system has CE Mark approval in
Europe and is also approved in China.
Cephalon Inc. (NASDAQ:CEPH), Frazer, Pa.
InnoPharmax Inc., Taipei, Taiwan
SymBio Pharmaceuticals Ltd., Tokyo, Japan
Eisai Co. Ltd. (Tokyo:4523; Osaka:4523), Tokyo, Japan
Mundipharma International Ltd., Cambridge, Mass.
Product: Levact (Ribomustin, Treanda) bendamustine (SDX-105)
Business: Cancer
The U.K.’s NICE issued final guidance recommending the use of
Levact bendamustine from Mundipharma as a first-line treatment for
patients with chronic lymphocytic leukemia (CLL) for whom fludarabine
combination chemotherapy is not appropriate — its approved indication. The guidance is in line with the agency’s December final appraisal
determination (see BioCentury, Jan. 3). The agency did not issue a
preliminary appraisal and said it proceeded straight to the final stage of
guidance development due to the strength of evidence presented for
the drug. The alkylating agent is also approved in the U.K. to treat nonHodgkin’s lymphoma (NHL), CLL and multiple myeloma (MM).
Astellas granted rights for bendamustine to Cephalon in the U.S.,
to Mundipharma in Europe and to SymBio in Japan and certain Asian
countries. Symbio then partnered the compound with Eisai in Japan,
South Korea and Singapore. Cephalon markets bendamustine as Treanda
See next page
Management
regional CFO for Europe and the Middle East at the Fresenius Kabi AG
subsidiary of Fresenius SE and managing director of Fresenius’ Fresenius
Kabi Deutschland GmbH subsidiary; he succeeds Dave Lemus, who is
departing
Allon Therapeutics Inc. (TSX:NPC), Vancouver, B.C.
Business: Neurology
Hired: Michael Gold as VP of clinical development and CMO, formerly
VP of neuroscience medicines at GlaxoSmithKline plc
Nexus Dx Inc., San Diego, Calif.
Hired: Gordon Sangster as VP of finance and CFO, formerly CFO of
Micrus Endovascular Corp., which was acquired by Johnson & Johnson
Amicus Therapeutics Inc. (NASDAQ:FOLD), Cranbury, N.J.
Business: Metabolic
Transitioned: Matthew Patterson to president, while remaining COO
Omni Bio Pharmaceutical Inc. (OTCBB:OMBP), Greenwood Village, Colo.
Business: Infectious, Endocrine, Transplant
Hired: James Crapo as CEO, formerly CEO of Aeolous Pharmaceuticals
Inc.; he replaces acting CEO Charles Dinarello, who will become CSO
and CMO
Cantargia AB, Lund, Sweden
Business: Cancer
Hired: Agneta Svedberg as CEO, formerly a senior advisor at Semcon AB
Fate Therapeutics Inc., San Diego, Calif.
Business: Gene/Cell therapy, Cancer, Musculoskeletal
Departing: Paul Grayson as president and CEO to form a newco
MorphoSys AG (Xetra:MOR), Martinsried, Germany
Business: Antibodies, Autoimmune, Cancer
Hired: Jens Holstein as CFO and a director, effective May 1, currently
Pearl Therapeutics Inc., Redwood City, Calif.
Business: Pulmonary, Inflammation
Hired: Chuck Bramlage as president, CEO and a director, formerly
president of pharmaceutical products of Covidien plc; he replaces
interim CEO Howie Rose, who will remain a director
QLT Inc. (TSX:QLT; NASDAQ:QLTI), Vancouver, B.C.
Business: Ophthalmic, Dermatology, Cancer
Regulatory,
from previous page
in the U.S. to treat CLL and indolent B cell NHL. Mundipharma markets
it as Ribomustin in Germany to treat CLL, NHL and MM.
CSL Ltd. (ASX:CSL), Melbourne, Australia
Product: Hizentra human immune globulin (IgPro20)
Business: Hematology
FDA approved an sBLA from CSL to extend the shelf life of Hizentra
human immune globulin (Ig) to 30 months from 24 months. The onceweekly, subcutaneous Ig replacement therapy is stable at room temperature and marketed to treat primary humoral immunodeficiency.
Delcath Systems Inc. (NASDAQ:DCTH), New York, N.Y.
Product: Melphalan delivered via Delcath’s PHP system
Business: Cancer
Delcath said FDA refused to file an NDA for melphalan delivered
using the Delcath Percutaneous Hepatic Perfusion (PHP) System to
treat melanoma metastatic to the liver. According to the company, the
agency requested information about the timing of manufacturing plant
inspections and product and sterilization validations, as well as additional safety information and statistical analyses. Delcath said it had
already planned to submit the requested safety information to the
agency in April. The biotech plans to request a formal meeting with FDA,
and expects to resubmit the NDA by Sept. 30. The NDA was submitted
under section 505(b)(2) of the Food, Drug and Cosmetic Act, which
allows sponsors to reference data on safety and efficacy from the
scientific literature or from previously approved products.
Product: Avastin bevacizumab (RG435)
Business: Cancer
FDA granted a hearing on June 28-29 to allow Genentech to present
arguments for maintaining accelerated approval of Avastin bevacizumab
for first-line treatment of HER2-negative metastatic breast cancer. The
Roche unit requested a hearing in December after FDA proposed to
remove the indication (see BioCentury, Jan. 3).
In a letter to the company, CBER Director Karen Midthun, who will
be the presiding officer at the hearing, said FDA’s Oncologic Drugs
Advisory Committee will be present at the hearing to review the issues
and provide advice and recommendations to the commissioner’s office.
ODAC has twice voted against Avastin in breast cancer. In 2007, the
panel voted 5-4 against accelerated approval for the indication; the
agency granted accelerated approval in 2008 despite the panel’s recommendations. FDA did, however, heed a 12-1 vote last year from ODAC
BioCentury Week in Review (formerly BioCentury Part II)
BioCentury Week in Review is published by
BIOCENTURY PUBLICATIONS INC.,
PO Box 1246 San Carlos CA 94070-1246. Phone 650-595-5333.
Fax 650-595-5589. David Flores, President & CEO;
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FEBRUARY 28, 2011
P AGE B10 OF 24
recommending removal of the breast cancer indication from Avastin’s
label (see BioCentury, Dec. 10, 2007; Feb. 25, 2008 & July 26, 2010).
Midthun also said the commissioner’s office has decided to observe
a “separation of function” for the proceedings even though such
separation is not required under the applicable regulations. This means
representatives of CDER may not participate or advise in any decision
except as witnesses in the hearing, unless the commissioner designates
such representatives as advisors in writing.
Genentech and CDER must submit a joint statement by March 23
outlining the facts that are not in dispute and the issues that are
disputed. Each party has until April 20 to submit a summary of arguments
it plans to make and its expectations of what the evidence will show.
The U.K.’s NICE issued final guidance recommending against the use
of Avastin bevacizumab from Roche in combination with a taxane for
first-line treatment of metastatic breast cancer. The guidance is in line
with a December final appraisal determination (FAD) (see BioCentury,
Dec. 13, 2010). NICE said the evidence for the effectiveness of Avastin
in prolonging survival was not robust and overall did not show enough
of a demonstrable benefit.
The mAb against VEGF is approved in the EU and U.S. for metastatic
colorectal cancer (mCRC), unresectable or metastatic non-small cell
lung cancer (NSCLC) and renal cell carcinoma (RCC), as well as for
glioblastoma multiforme (GBM) in the U.S. Avastin is also approved in
the EU to treat metastatic breast cancer, while FDA has proposed to
withdraw the indication in the U.S. (see BioCentury, Jan. 24). EMA’s CHMP
began reviewing the benefit-risk profile of Avastin for the indication in
September (see BioCentury, Sept. 27, 2010). Roche’s Genentech Inc. unit
markets Avastin in the U.S., while Roche markets it elsewhere.
Product: Votrient pazopanib
Business: Cancer
The U.K.’s NICE issued final guidance recommending the use of
Votrient pazopanib from GlaxoSmithKline as a first-line treatment for
patients with advanced renal cell carcinoma (RCC) who have not
received prior cytokine therapy. The guidance is in line with the
agency’s December final appraisal determination (FAD) (see BioCentury,
Jan. 3). The agency proceeded straight to the final stage of guidance
development and did not issue a preliminary appraisal for the broadspectrum inhibitor of VEGF and other tyrosine kinases, which has
conditional approval for the first-line treatment of RCC and for patients
who received prior cytokine therapy for advanced disease.
GSK agreed to a 2-part patient access scheme under which the
pharma will offer Votrient at a 12.5% discount along with a possible
undisclosed rebate linked to the outcome of the head-to-head Phase
III COMPARZ trial comparing Votrient with Sutent sunitinib from Pfizer
Inc. (NYSE:PFE, New York, N.Y.). NICE said the 2-part scheme makes
Votrient a cost-effective option for the NHS.
HRA Pharma S.A., Paris, France
Product: NorLevo levonorgestrel (SOH-075)
Business: Endocrine
Japan’s Ministry of Health, Labor and Welfare (MHLW) approved
NorLevo levonorgestrel as an emergency contraceptive. Aska Pharmaceutical Co. Ltd. (Tokyo:4514, Tokyo, Japan) is expected to launch the
contraceptive in Japan in mid-May. Aska has Japanese marketing rights
under a November 2009 deal with Sosei Group Corp. (Tokyo:4565,
Tokyo, Japan), which has exclusive distribution rights in Japan and
Australia from HRA Pharma under a 2001 deal (see BioCentury, Oct. 27,
2008). NorLevo was launched in Europe in 1999 and is approved in about
50 countries.
See next page
Regulatory,
from previous page
Ligand Pharmaceuticals Inc. (NASDAQ:LGND), San Diego, Calif.
Product: Promacta eltrombopag
FDA granted full approval to Promacta eltrombopag from
GlaxoSmithKline to treat chronic idiopathic thrombocytopenic purpura (ITP). In 2008, FDA granted accelerated approval to the small
molecule thrombopoietin (TPO) receptor agonist. Promacta is approved in Europe, Japan, Venezuela, Kuwait, Chile and Russia. GSK has
worldwide rights to the drug from Ligand.
Product: Naproxcinod (HCT 3012)
NicOx said it plans to start the formal dispute resolution process
this quarter to appeal a July complete response letter for an NDA for
naproxcinod to treat signs and symptoms of osteoarthritis (OA).
Further details were not disclosed. In the letter, FDA recommended
NicOx conduct 1 or more long-term controlled studies to assess
cardiovascular and gastrointestinal safety of the compound. The agency
also recommended additional studies to demonstrate a clinically meaningful therapeutic benefit attributable to nitric oxide donation (see
Last May, a joint FDA panel voted 16-1, with 1 abstention, against
approval of naproxcinod (see BioCentury, May 17). Naproxcinod is a
cyclooxygenase (COX)-inhibiting nitric oxide donator (CINOD) that
releases naproxen and nitric oxide.
Product: Rasilamlo (Tekamlo - U.S.) aliskiren/amlodipene
Business: Cardiovascular
EMA’s CHMP issued a positive opinion recommending approval of
an MAA from Novartis for Rasilamlo aliskiren/amlodipine to treat
hypertension in patients not adequately controlled with Novartis’
Tekturna aliskiren or amlodipine alone. Rasilamlo is a single-pill
combination of Tekturna, a renin inhibitor, and amlodipine, a calcium
channel blocker. Rasilamlo is approved as Tekamlo in U.S. for the same
indication. Tekturna is approved in over 80 countries, including the U.S.
and countries of the EU.
Novo Nordisk A/S (CSE:NVO; NYSE:NVO), Bagsvaerd, Denmark
Product: RFXIII (NN1814)
Novo Nordisk submitted a BLA to FDA for rFXIII to treat congenital
Factor XIII deficiency, a bleeding disorder. Novo plans to submit an
MAA for the recombinant Factor XIII in Europe next quarter. Novo has
rights to rFXIII from ZymoGenetics Inc., which was acquired by BristolMyers in October (see BioCentury, Oct. 18, 2010).
Orexo AB (SSE:ORX), Uppsala, Sweden
Paladin Labs Inc. (TSX:PLB), Montreal, Quebec
Kyowa Hakko Kirin Co. Ltd. (Tokyo:4151), Tokyo, Japan
Product: Abstral fentanyl (EN 3267, KW-2246)
Business: Neurology
Paladin said Health Canada approved Abstral fentanyl to treat
breakthrough pain in patients receiving opioid analgesics for underlying
chronic cancer pain. The company plans to launch the sublingual
mucoadhesive fentanyl next quarter. Orexo granted Paladin rights to
FEBRUARY 28, 2011
P AGE B11 OF 24
Abstral in Canada, ProStrakan rights in Europe and the U.S., and Kyowa
rights in Japan. Abstral is already marketed in Europe and was approved
in the U.S. last month.
Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan
Product: Abilify aripiprazole
Business: Neurology
FDA approved Abilify aripiprazole as an adjunct to lithium or
valproate for the maintenance treatment of bipolar I disorder. Abilify
is already approved in the U.S to treat schizophrenia, irritability
associated with autistic disorder, manic and mixed episodes associated
with bipolar I disorder as monotherapy or as an adjunct to lithium or
valproate, as maintenance treatment of bipolar I disorder, and as
adjunctive treatment of major depressive disorder (MDD). Abilify is a
small molecule partial agonist of the dopamine D2 and serotonin (5HT1A) receptors and antagonist of the serotonin (5-HT2A) receptor.
Bristol-Myers co-promotes the drug in the U.S. and EU.
Product: Tygacil tigecycline
EMA’s CHMP recommended updating the label for Pfizer’s Tygacil
tigecycline to include a warning that the glycylcycline antibiotic has been
associated with an increased mortality in clinical studies. CHMP said
Tygacil’s benefits continue to outweigh its risk, but that it should only
be used for its approved indications — complicated skin and skin
structure infections (cSSSIs) and complicated intra-abdominal infections — and only when other antibiotics are not suitable.
Protalix Biotherapeutics Inc. (NYSE-A:PLX; Tel Aviv:PLX), Carmiel,
Israel
Product: Taliglucerase alfa (formerly prGCD)
Business: Metabolic
FDA issued a complete response letter for an NDA from Protalix
for Gaucher’s disease candidate taliglucerase alfa. According to the
company, the agency requested CMC information about testing specifications and assay validation, as well as additional data from ongoing
switchover and extension studies, but did not request additional trials.
Protalix said at the time of the NDA submission full data from those
ongoing trials were not available. Protalix, which plans to request a
meeting with the agency, said it has preliminary data from the trials that
it believes will satisfy FDA’s request. Pfizer has exclusive, worldwide
rights to the plant cell-expressed recombinant form of human
glucocerebrosidase (GCase) outside of Israel.
Provepharm S.A.S., Marseille, France
Product: Proveblue methylthioninium chloride
EMA’s CHMP issued a positive opinion recommending approval of
an MAA from Provepharm for Proveblue methlythioninium chloride for
the acute symptomatic treatment of methemoglobinemia induced by
medicinal and chemical products.
R-Biopharm AG, Darmstadt, Germany
Product: Ridascreen Novovirus ELISA
FDA approved R-Biopharm’s Ridascreen Norovirus ELISA for the
preliminary detection of norovirus in multiple subjects with simultaneously-contracted gastroenteritis when there is a clear avenue of
virus transmission. The third generation, stool-based, anti-norovirus
See next page
Regulatory,
from previous page
mAb ELISA diagnostic was reviewed under a de novo pathway, an
alternative path to market for devices that are lower risk and may not
require a PMA, but are of a new type and would not be cleared in a 510(k)
premarket notification. The agency said that the test is not sensitive
enough for use when only a single person has symptoms and should not
be used for individual diagnoses.
Regeneron Pharmaceuticals Inc. (NASDAQ:REGN), Tarrytown, N.Y.
Product: VEGF Trap-Eye
Business: Ophthalmic
Regeneron submitted a BLA to FDA for VEGF Trap-Eye to treat
wet age-related macular degeneration (AMD). The biotech requested Priority Review for the human fusion protein that binds all
forms of VEGF-A and placental growth factor (PIGF). Bayer plans
to submit a regulatory application in Europe this half. Regeneron
and Bayer share commercialization rights to VEGF Trap-Eye outside the U.S., while Regeneron has exclusive U.S. rights (see
BioCentury, Oct. 23, 2006).
Salix Pharmaceuticals Ltd. (NASDAQ:SLXP), Morrisville, N.C.
Product: Xifaxan rifaximin
Business: Gastrointestinal
Salix said it expects to receive a complete response letter for
Xifaxan rifaximin 550 mg tablets based on a telephone conversation
with the agency about the irritable bowel syndrome (IBS) candidate.
Salix attributed the expected setback to FDA’s “newly expressed need
for retreatment information;” however, the company said it only has
limited information about the letter’s content at this time. The sNDA
is under review to treat non-constipation IBS and IBS-related bloating
with a March 7 PDUFA date.
The non-absorbed broad-spectrum antibiotic is already marketed in the U.S. to reduce the risk of overt hepatic encephalopathy
(HE) recurrence in patients with advanced liver disease. Salix
markets a 200 mg formulation of Xifaxan in the U.S. to treat
travelers’ diarrhea.
sanofi-aventis Group (Euronext:SAN; NYSE:SNY), Paris, France
Product: Apidra insulin glulisine
Business: Endocrine
sanofi-aventis received 2 warning letters from FDA regarding
the company’s failure to adequately address cGMP deficiencies and
postmarketing reporting violations identified during FDA inspections last year. The pharma has 15 days from the receipt of the
letters to respond with specific steps to correct the violations.
FDA said sanofi failed to submit adverse event reports within 15
days of receiving the initial report for several drugs, including atrial
fibrillation (AF) drug Multaq dronedarone. The agency said the
cGMP violations, which include concerns about environmental
contaminants associated with marketed diabetes drug Apidra insulin glulisine, were identified at the company’s manufacturing facility
in Frankfurt am Main, Germany. Multaq is a multichannel blocker
with properties of antiarrhythmics in Vaughan-Williams classes IIV and Apidra is a human insulin analog produced by recombinant
DNA technology.
Product: Multaq dronedarone
sanofi-aventis received 2 warning letters from FDA regarding the
company’s failure to adequately address cGMP deficiencies and
FEBRUARY 28, 2011
P AGE B12 OF 24
postmarketing reporting violations identified during FDA inspections
last year. The pharma has 15 days from the receipt of the letters to
respond with specific steps to correct the violations. FDA said sanofi
failed to submit adverse event reports within 15 days of receiving the
initial report for several drugs, including atrial fibrillation (AF) drug
Multaq dronedarone. The agency said the cGMP violations, which
include concerns about environmental contaminants associated with
marketed diabetes drug Apidra insulin glulisine, were identified at the
company’s manufacturing facility in Frankfurt am Main, Germany. Multaq
is a multichannel blocker with properties of antiarrhythmics in VaughanWilliams classes I-IV and Apidra is a human insulin analog produced by
recombinant DNA technology.
Sunesis Pharmaceuticals Inc. (NASDAQ:SNSSD), South San Francisco,
Calif.
Product: Vosaroxin (formerly SNS-595, voreloxin)
Business: Cancer
FDA granted Fast Track designation for Sunesis’ vosaroxin to treat
relapsed or refractory acute myelogenous leukemia (AML) in combination with cytarabine. The quinolone derivative that intercalates DNA
and inhibits topoisomerase II (TOP2) is in Phase III testing for the
indication and has Orphan Drug designation in the U.S.
Takeda Pharmaceutical Co. Ltd. (Tokyo:4502), Osaka, Japan
Product: Azilsartan medoxomil/chlorthalidone
Takeda submitted an NDA to FDA for a fixed-dose combination
of azilsartan medoxomil (TAK-491) plus chlorthalidone to treat
hypertension. Azilsartan is an angiotensin II type 1 (AT1) receptor
blocker and chlorthalidone is a long-acting oral thiazide-like diuretic. Azilsartan as a single agent is approved by FDA and under
review by EMA for hypertension.
Product: Edarbi azilsartan medoxomil (TAK-491)
FDA approved an NDA from Takeda for Edarbi azilsartan medoxomil
to treat hypertension. The angiotensin II type 1 (AT1) receptor blocker
is also under EMA review.
ViroPharma Inc. (NASDAQ:VPHM), Exton, Pa.
Product: Cinryze (formerly C1-INH)
ViroPharma said it plans to submit a response next quarter to
an October 2010 complete response letter from FDA about the
expansion of industrial scale manufacturing for Cinryze. In the
letter, ViroPharma said FDA requested responses to quality observations during a pre-approval inspection, as well as additional
information and supporting documentation about the technical
processes (see BioCentury, Oct. 25, 2010). The complement 1 (C1)
esterase inhibitor is approved in the U.S. to prevent angioedema
attacks in patients with hereditary angioedema (HAE). An MAA is
under review in the EU for the indication. ViroPharma expects an
opinion from EMA’s CHMP on the application in March.
ViroPharma submitted responses to Day 180 questions from
EMA’s CHMP related to an MAA for Cinryze to prevent angioedema
attacks in patients with hereditary angioedema (HAE). The company expects an opinion from CHMP on the application for the
complement 1 (C1) esterase inhibitor in March. Cinryze has Orphan designation in the EU to treat angioedema caused by C1
inhibitor deficiency and is approved in the U.S. to prevent angioedema attacks in patients with HAE.
See next page
Clinical News,
from previous page
CLINICAL RESULTS
Advancell Advanced In Vitro Cell Technologies S.A., Barcelona,
Spain
Product: Acadra acadesine (ATH001)
Business: Cancer
Molecular target: NA
Description: Small molecule that induces apoptosis independent of p53
status
Indication: Treat chronic lymphocytic leukemia (CLL)
Endpoint: Safety
Status: Phase I/IIa data
Milestone: NA
An open-label, dose-escalation, European Phase I/IIa trial in 24
patients with relapsed or refractory CLL showed that Acadra was well
tolerated and led to reductions in leukemic tumor burden. Additionally,
7 of 9 patients treated with the optimal biologic dose of Acadra had a
reduction in absolute B cell count, a reduction of clinically palpable
lymphadenopathies or both. No grade 3 or 4 adverse events occurred
at the optimal biologic dose of Acadra.
Amgen Inc. (NASDAQ:AMGN), Thousand Oaks, Calif.
Daiichi Sankyo Co. Ltd. (Tokyo:4568; Osaka:4568), Tokyo, Japan
Product: Denosumab (Prolia, Xgeva) (AMG 162)
Business: Cancer
Molecular target: Receptor activator of NF-kappa B ligand (RANKL)
(TNFSF11)
Description: Human mAb targeting receptor activator of NF-kappa B
ligand (RANKL)
Indication: Treat bone metastases in patients with advanced prostate
cancer
Endpoint: Time to first on-study Skeletal Related Event (SRE); delay in
time to first SRE, time to first and subsequent on-study SREs and safety
Status: Additional Phase III data
Milestone: NA
Additional data from a double-blind, head-to-head, international Phase III trial in 1,901 patients with advanced prostate cancer
showed that the median time to first on-study SRE, the primary
endpoint, was 20.7 months for denosumab vs. 17.1 months for
Zometa (p=0.0002 for non-inferiority and p=0.008 for superiority). Patients received 120 mg subcutaneous denosumab or 4 mg
Zometa as a 15-minute infusion every 4 weeks. Data were published in The Lancet. Amgen previously reported that denosumab
met the primary endpoint of non-inferiority to Zometa in time to
the first on-study SRE, and also met the secondary endpoints of
superiority to Zometa in time to first SRE and time to the first and
subsequent on-study SREs (see BioCentury, Feb. 15, 2010).
Last November, FDA approved an sBLA from Amgen for denosumab
as Xgeva to prevent SREs in patients with bone metastases from solid
tumors. Denosumab is also approved in the U.S. and EU as Prolia to treat
osteoporosis in postmenopausal women and in the EU to treat bone loss
associated with hormone ablation in men with prostate cancer.
GlaxoSmithKline plc (LSE:GSK; NYSE:GSK, London, U.K.) has rights to cocommercialize denosumab for postmenopausal osteoporosis in Europe,
Australia, New Zealand and Mexico (see BioCentury, Aug. 3, 2009). Daiichi
Sankyo has Japanese rights to denosumab to treat postmenopausal osteoporosis and bone-metastatic cancers. Novartis AG (NYSE:NVS;
SIX:NOVN, Basel, Switzerland) markets Zometa in the U.S. and EU to treat
bone metastases and bone complications in cancer patients.
FEBRUARY 28, 2011
P AGE B13 OF 24
Aoxing Pharmaceutical Co. Inc. (NYSE-A:AXN), Shijiazhuang, China
QRxPharma Ltd. (ASX:QRX; OTCQX:QRXPY), Sydney, Australia
Product: MoxDuo IR morphine/oxycodone (Q8003IR)
Business: Neurology
Molecular target: Mu opioid receptor (OPRM1) (MOR)
Description: Immediate-release combination of oxycodone and morphine
Indication: Treat moderate to severe post-operative pain following
total knee replacement surgery
Endpoint: Summed pain intensity difference (SPID) from baseline over
48 hours; safety
Status: Phase III data
Milestone: Submit NDA (1H11)
The double-blind, U.S. Phase III Study 009 trial in 142 patients
undergoing total knee replacement surgery showed that a flexible-dose
regimen of MoxDuo IR met the primary endpoint of significantly
improving SPID scores from baseline over 48 hours vs. a fixed, lowdose regimen of MoxDuo IR (p<0.02). The flexible-dose regimen of
MoxDuo IR consisted of 6 mg morphine/4 mg oxycodone up to 24 mg
morphine/16 mg oxycodone every 4 to 6 hours for 48 hours, while the
fixed-dose regimen started with a loading dose of 6 mg morphine/4 mg
oxycodone and was followed by 3 mg morphine/2 mg oxycodone every
4 to 6 hours for 48 hours. All patients received IV morphine for up to
24 hours following surgery. Patients were eligible to continue dosing
after the initial treatment period as an outpatient for up to 10 days.
QRxPharma said a pre-NDA meeting with FDA is scheduled for March
22. Aoxing Pharmaceutical has exclusive rights from QRxPharma to
develop and commercialize MoxDuo IR in China (see BioCentury,
March 1, 2010).
Aprea AB, Stockholm, Sweden
Product: PRIMA-1MET (APR-246)
Business: Cancer
Molecular target: p53
Description: Small molecule quinuclidinone that promotes correct
folding of p53
Indication: Treat refractory hematologic malignancies or prostate
cancer
Endpoint: Dose-limiting toxicities (DLTs); safety and pharmacokinetics
Status: Phase I/II data
Milestone: NA
An open-label, dose-escalation, Swedish Phase I/II trial in 22 patients showed that 2-hour infusions of IV APR-246 were safe and only
produced DLTs at plasma levels above predicted therapeutic levels.
Axcan Pharma Inc., Mont St. Hilaire, Quebec
Product: Pylera
Molecular target: Ribosomal 30S subunit
Description: Triple therapy capsule containing bismuth subcitrate
potassium, metronidazole and tetracycline
Indication: Treat Helicobacter pylori infection
Endpoint: H. Pylori eradication as confirmed by urea breath test at weeks
6 and 10; safety
Milestone: NA
An open-label, European Phase III trial in 440 patients showed that
Pylera plus omeprazole for 10 days was superior to standard of care
(SOC; omeprazole, amoxicillin and clarithromycin) for 7 days on the
primary endpoint of H. Pylori eradication rate as confirmed by a urea
breath test at weeks 6 and 10 (80% vs. 55%, p<0.0001). The safety
profiles for both treatment arms were similar, with gastrointestinal and
See next page
Clinical Results,
from previous page
CNS disorders reported as the main adverse events. Data were
published in The Lancet. Axcan markets Pylera in the U.S. for the
indication.
Bellicum Pharmaceuticals Inc., Houston, Texas
Product: BPX-101 (formerly BP-GMAX-CD1)
Business: Cancer
Description: Genetically-modified autologous dendritic cell-based
cancer vaccine
Indication: Treat metastatic castration-resistant prostate cancer (CRPC)
Endpoint: Safety and maximum tolerated dose (MTD); pharmacokinetics, immune response, clinical response, prostate specific antigen
(PSA) response, circulating tumor cells (CTC), cancer-related pain, pain
medication usage and preliminary antitumor activity
Status: Additional Phase I/II data
Milestone: Start Phase II (2011)
Additional data from an open-label, dose-escalation, U.S. Phase I/
II trial in 12 patients showed that low-, mid- and high-doses of
intradermal BPX-101 given every other week in combination with
AP1903 for 6 doses produced a partial or complete response in 3
patients. Additionally, 2 patients experienced a PSA decline approaching 50% within the first 12 weeks of treatment. Data were presented
at the American Society of Clinical Oncology Genitourinary Cancers
Symposium in Orlando.
Bellicum previously reported interim data from 6 evaluable patients
showing that low- and mid-dose BPX-101 plus AP1903 produced 4 cases
of stable disease at 12 weeks (see BioCentury, April 26, 2010). Ariad
Pharmaceuticals Inc. (NASDAQ:ARIA, Cambridge, Mass.) granted
Bellicum a non-exclusive license to AP1903, a homodimerizing compound that activates genetically engineered receptors on cell therapies,
for use in cancer vaccines in 2006 (see BioCentury, Oct. 16, 2006).
Biogen Idec Inc. (NASDAQ:BIIB), Weston, Mass.
Elan Corp. plc (NYSE:ELN), Dublin, Ireland
Product: Tysabri natalizumab
Molecular target: Integrin alpha(4) (VLA-4 ) (CD49D)
Description: Humanized mAb against integrin alpha(4)
Indication: Treat multiple sclerosis (MS)
Endpoint: NA
Status: Postmarketing study data
Milestone: NA
As of Feb. 2, Biogen Idec said that there have been 95 confirmed
cases of progressive multifocal leukoencephalopathy (PML) in patients
receiving Tysabri monotherapy for MS since the drug was relaunched
in the U.S. and its first international approval in 2006. As of Dec. 31,
2010, Biogen Idec reported that approximately 78,800 patients have
been treated with Tysabri in the post-marketing setting.
In December, Biogen Idec and partner Elan submitted an sBLA to
FDA and a Type II variation to the EMA to update the label of Tysabri
to include anti-JCV antibody status as 1 potential factor to help stratify
the risk of PML. The anti-JCV antibodies are believed to be a risk factor
for developing PML (see BioCentury, Jan. 3).
Last year, FDA updated the label and medication guide for Tysabri
to warn that the risk of developing PML increases with the number of
infusions received (see BioCentury, Feb. 15, 2010). Last July, Biogen Idec
updated the U.S. label for Tysabri to warn that the risk of PML increases
in patients with prior immunosuppressant use and that the increased
risk appears to be independent of Tysabri treatment duration (see
FEBRUARY 28, 2011
P AGE B14 OF 24
BioCentury, July 26, 2010). The companies originally withdrew the drug
in February 2005 because its use was associated with PML. Elan and
Biogen Idec market Tysabri to treat MS in the EU and to treat MS and
Crohn’s disease in the U.S.
Chimerix Inc., Durham, N.C.
Product: CMX001
Description: Oral phospholipid intramembrane microfluidization (PIM)conjugate chemical modification of cidofovir, a dsDNA viral synthesis
inhibitor
Indication: Treat adenovirus infection in immunocompromised transplant patients
Endpoint: NA
Status: NA data
Milestone: NA
Chimerix reported data from a 12-year old severely
immunocompromised bone marrow transplant patient with adenovirus
infection showing that treatment with oral CMX001 under emergency-use
IND provisions reduced viral load to undetectable levels and improved
renal and hepatic function within 5 weeks of starting treatment. Within
8 weeks, the patient was transferred out of intensive care, hemodialysis
was discontinued, and the patient’s GI bleeding and renal impairment were
resolved. CMX001 was well tolerated with no serious adverse events
reported. Data were published in the Journal of Clinical Virology. CMX001
is in Phase II testing to treat or prevent cytomegalovirus (CMV) infection
in hematopoietic stem cell transplant recipients.
Dynavax Technologies Corp. (NASDAQ:DVAX), Berkeley, Calif.
Product: N8295 (formerly M2e/NP-ISS)
Molecular target: Matrix protein 2 extracellular domain (M2e)
Description: Immunostimulatory sequence linked to a nucleoprotein
(NP) and the matrix protein 2 extracellular domain (M2e)
Indication: Vaccinate against influenza virus infection
Endpoint: Safety
Status: Phase Ib data
Milestone: NA
An open-label, U.S. Phase Ib trial in 15 healthy volunteers showed
that 3 doses of N8295 given a month apart plus an undisclosed
investigational H5N1 avian influenza vaccine from Novartis AG
(NYSE:NVS; SIX:NOVN, Basel, Switzerland) were well tolerated with
no serious adverse events reported. Additionally, all N8295 dose
groups produced antibody and cellular immune responses to NP and
antibody responses to M2e. Data were presented at the Evaluation of
Pandemic Influenza Vaccines in Clinical Trials meeting in Geneva. N8295
is a component of Dynavax’s Universal Flu vaccine. Novartis has an
option to negotiate an agreement to develop and commercialize the
universal vaccine (see BioCentury, July 28, 2008).
Fate Therapeutics Inc., San Diego, Calif.
Product: FT1050
Molecular target: Prostaglandin E2 (PGE2) receptor
Description: Small molecule prostaglandin E2 analog
Indication: Hematopoietic stem cell (HSC) support in patients undergoing non-myeloablative therapy
Endpoint: Safety; time to engraftment, rates of acute and chronic graftversus-host disease (GvHD), 30- and 100-day treatment-related mortality, measures of immune reconstitution, and relapse-free and overall
survival (OS) at 1 and 2 years post-transplantation
See next page
Clinical Results,
from previous page
Status: Preliminary Phase Ib data
Milestone: NA
Preliminary data from an open-label, U.S. Phase Ib trial in 15
evaluable patients with hematologic malignancies who have undergone
non-myeloablative conditioning therapy showed that dual umbilical
cord blood transplantation with hematopoietic stem cells treated ex
vivo with FT1050 had a similar safety profile to that of a standard double
umbilical cord blood transplant. In 6 evaluable patients who received
an umbilical cord blood unit using an FT1050-treatment protocol
designed to enhance activity, the average time to engraftment was 18.5
days vs. 21 days for a historical average, and 5 of 6 patients engrafted
with the FT1050-treated cord blood unit. The other 9 patients received
an umbilical cord blood unit using an earlier version of the FT1050treatment protocol that the company said was designed to assess safety.
There was 1 case of ≥grade 2 acute GvHD. Patients received 2 umbilical
cord blood units for hematopoietic reconstitution — 1 treated ex vivo
at the point-of-care with FT1050 and 1 untreated. The trial is enrolling
21 patients. Data were presented at the BMT Tandem Meetings in
Honolulu. FT1050 has Orphan Drug designation in the U.S. for the ex
vivo treatment of human allogeneic stem cells to enhance stem cell
engraftment by treating neutropenia, thrombocytopenia, lymphopenia
and anemia.
Genzyme Corp. (NASDAQ:GENZ), Cambridge, Mass.
Product: Eliglustat tartrate (formerly Genz-112638)
Business: Metabolic
Molecular target: Glucosylceramide synthase (GCS)
Description: Ceramide analog that inhibits glucosylceramide synthase (GCS)
Indication: Treat Type I Gaucher’s disease
Endpoint: Change in hemoglobin levels, platelet levels and spleen
volume; change in liver volume, biomarkers and quality of life
Status: Additional Phase II data
Milestone: NA
Three-year data from an open-label, international Phase II trial in
19 evaluable patients showed that oral eliglustat decreased spleen and
liver volumes from baseline by 61% and 29%, respectively, increased
mean hemoglobin levels by 2.6 g/dL and increased platelet counts by
91%. Data were presented at the Lysosomal Disease Network World
Symposium in Las Vegas.
Genzyme previously reported that eliglustat met the composite
primary endpoint of a clinically meaningful response at 12 months in at
least 2 of 3 endpoints: change in hemoglobin levels, platelet levels and
spleen volume (see BioCentury, Feb. 23, 2009). The company also previously reported 6- and 12-month and 2-year data from the trial (see
BioCentury, May 12, 2008 & Feb. 15, 2010). The Phase III ENGAGE, EDGE
and ENCORE trials of eliglustat for the indication are ongoing.
Iris International Inc. (NASDAQ:IRIS), Chatsworth, Calif.
Product: NADiA ProsVue
Description: Assay designed to detect prostate specific antigen (PSA)
levels using nucleic acid-labeled antibodies and PCR
Indication: Predict risk of prostate cancer recurrence following radical
prostatectomy
Endpoint: Sensitivity, specificity, positive predictive value (PPV) and
negative predictive value (NPV)
Status: Pivotal trial data
Milestone: NA
FEBRUARY 28, 2011
P AGE B15 OF 24
A retrospective U.S. pivotal trial in 392 post-radical prostatectomy patients with PSA levels <100 pg/mL showed that Iris’
NADiA ProsVue test had 75% sensitivity and 96.6% specificity for
detecting patients with a low risk of cancer recurrence. The PPV
and NPV were 81.4% and 95.2%, respectively. Data were presented
at the American Society of Clinical Oncology Genitourinary Cancers Symposium in Orlando. Last April, Iris submitted a 510(k)
application to FDA for the assay to identify patients at low risk of
cancer recurrence post-radical prostatectomy.
Isis Pharmaceuticals Inc. (NASDAQ:ISIS), Carlsbad, Calif.
Product: ISIS-CRPRx (ISIS 353512)
Molecular target: C-reactive protein (CRP)
Description: Second-generation antisense inhibitor that targets Creactive protein (CRP)
Indication: Treat inflammatory diseases
Endpoint: Safety; pharmacokinetics and pharmacodynamics
Status: Phase I data
Milestone: NA
Data from the cohort of 8 subjects with elevated baseline CRP
levels (3 mg/L) in a double-blind, dose-escalation Phase I trial
showed that weekly 600 mg ISIS-CRPRx significantly reduced CRP
levels by >70% vs. placebo after only 3 weeks. Specifically, CRP
levels in subjects receiving ISIS-CRPRx were reduced to a mean of
0.76 mg/L at week 3, whereas CRP levels in subjects receiving
placebo remained elevated above 3 mg/L (p<0.05). Single and
multiple ascending-doses of weekly 50-600 mg ISIS-CRPRx were
well tolerated in all 80 healthy volunteers, and no serious adverse
events were reported. The remaining 72 subjects had normal levels
of CRP (<2 mg/L). Isis said it plans to initially evaluate the compound
for use in multiple myeloma (MM) and rheumatoid arthritis (RA).
Medivir AB (SSE:MVIR B), Huddinge, Sweden
Product: TMC435 (formerly TMC435350)
Molecular target: HCV NS3 protease; Non-structural protein 4A
(NS4A)
Description: HCV NS3/4A protease inhibitor
Indication: Treat HCV infection in treatment-naïve patients
Endpoint: Proportion of patients achieving a sustained virologic response (SVR) defined as undetectable HCV RNA levels (<25 IU/mL) 24
weeks after the end of treatment; antiviral activity and safety
Status: Additional Phase IIb data
Milestone: Additional Phase IIb data (2Q11)
Additional data from the ongoing, double-blind, placebo-controlled,
international Phase IIb PILLAR (TMC435-C205) trial in 386 treatmentnaïve patients with chronic HCV genotype 1 infection showed that
83.6%, 76.1%, 83.1% and 84.4% of patients in each of the 4 TMC435
regimens - 75 mg TMC435 for 12 weeks, 75 mg TMC435 for 24 weeks,
150 mg TMC435 for 12 weeks and 150 mg TMC435 for 24 weeks -,
respectively, achieved an SVR defined as undetectable HCV RNA levels
(<25 IU/mL) 24 weeks after the end of treatment (n=288). Patients in
the placebo arm are continuing to receive standard of care (SOC;
Pegasys peginterferon alfa-2a and Copegus ribavirin) until week 48 and
SVR data from 24 weeks are not yet available. Additionally, 87.2%,
86.5%, 84.9% and 88.5% in each of the 4 TMC435 regimens, respectively,
achieved an SVR 4 weeks after the end of treatment (n=303) vs. 71.2%
for placebo (n=59).
Patients received 75 or 150 mg once-daily TMC435 for 12 or 24
weeks in combination with SOC for 24 weeks, or placebo plus SOC for
See next page
Clinical Results,
from previous page
24 weeks followed by SOC for an additional 24 weeks. TMC435-treated
patients who did not meet the predefined stopping criteria at week 24
continued with SOC for an additional 24 weeks. The partners previously reported that 79-86% of patients receiving TMC435 were able to
stop all therapy at week 24 after meeting predefined response criteria
of achieving undetectable HCV RNA levels at week 4 and at weeks 12,
16 and 20 (see BioCentury, Nov. 8, 2010).
Additional data from the Phase IIb ASPIRE (C206) trial of TMC435
in 462 treatment-experienced patients with HCV genotype 1 infection
are expected in 2Q11. The Phase III QUEST-1, QUEST-2 and PROMISE
trials of TMC435 are also ongoing. J&J’s Tibotec Pharmaceuticals Ltd.
unit has ex-Nordic rights to develop and commercialize TMC435 from
Medivir. Roche (SIX:ROG; OTCQX:RHHBY, Basel, Switzerland) markets Pegasys and Copegus.
Mitsubishi Tanabe Pharma Corp. (Tokyo:4508; Osaka:4508), Osaka,
Japan
Product: Gilenya fingolimod (FTY720)
Molecular target: Sphingosine 1-phosphate (S1P) receptor
Description: Sphingosine 1-phosphate (S1P) receptor agonist
Indication: Treat relapsing multiple sclerosis (MS)
Endpoint: Safety; incidence of macular edema, incidence of
bradyarrhythmic electrocardiograms and patient-reported outcomes
Milestone: NA
Novartis reported that a potential case of toxoplasmosis occurred in
1 patient receiving Gilenya at a German site in an ongoing, open-label,
international Phase III trial to treat relapsing MS. The pharma said that
laboratory testing has not confirmed the toxoplasmosis infection, nor has
a role for Gilenya been confirmed or excluded. Novartis said it does not
plan to issue a “Dear Healthcare Professional” letter regarding the adverse
event at this time, and is currently gathering all of the details of the case.
Last month, EMA’s CHMP issued a positive opinion recommending
approval of an MAA for Gilenya to treat relapsing-remitting multiple
sclerosis (RRMS). The product is already approved in the U.S. for the
indication. Novartis has rights to Gilenya from Mitsubishi Tanabe.
Neovacs S.A. (Euronext:ALNEV), Paris, France
Product: TNF-Kinoid (formerly TNFalpha kinoid)
Molecular target: Tumor necrosis factor (TNF) alpha
Description: Immunotherapy against tumor necrosis factor (TNF) alpha
Indication: Treat Crohn’s disease (CD)
Endpoint: Safety and immunogenicity; disease remission as measured by
Crohn’s Disease Activity Index (CDAI) score
Status: Additional Phase I/II data
Milestone: NA
Additional data from the open-label, dose-escalation, South African
and Swiss Phase I/II TNF-K-001 trial in 21 patients showed that the
presence of TNF antibodies at week 8 that were induced by treatment
with intramuscular TNF-Kinoid was associated with an increased
probability of clinical remission at week 12. Specifically, patients with
TNF antibodies at week 8 (n=14) had a >50% chance of being in clinical
remission at week 12, whereas patients without TNF antibodies at
week 8 (n=7) had a 14% chance of clinical remission at week 12. Neovacs
previously reported that that 60 (n=3), 180 (n=9) and 360 ug (n=9) doses
of TNF-Kinoid on days 0, 7 and 28 induced an anti-TNF antibody
response in 1, 8 and 8 patients, respectively (see BioCentury, Jan. 3).
FEBRUARY 28, 2011
P AGE B16 OF 24
Novavax Inc. (NASDAQ:NVAX), Rockville, Md.
Product: H1N1 VLP influenza vaccine
Description: Swine influenza A (H1N1) virus-like particle (VLP) vaccine
Indication: Vaccinate against swine influenza A (H1N1) infection
Endpoint: Safety and immunogenicity as measured by serum hemagglutinin inhibition (HAI) antibody titer response
Status: Final Phase II data
Milestone: NA
Final data from 1,013 healthy volunteers ages 18-64 in the first stage
of a double-blind, placebo-controlled, Mexican pivotal Phase II trial
showed that 5, 15 and 45 µg doses of Novavax’s 2009 swine influenza
A (H1N1) VLP vaccine produced seroconversion rates, defined as a ≥4fold increase in HAI titer from baseline, of 48.3%, 65% and 74.9%,
respectively, at day 14 vs. 5.9% for placebo. Additionally, low-, mid- and
high-doses of the vaccine produced seroprotection rates, defined as
the proportion of patients who achieved HAI titers ≥1:40 postvaccination, of 81.6%, 90.5% and 91.6%, respectively, at day 14. Data
were presented at the Evaluation of Pandemic Influenza Vaccines in
Clinical Trials meeting in Geneva. The second stage of the trial enrolled
3,547 healthy volunteers to evaluate the safety of a single 15 ug dose
of the vaccine.
Novavax previously reported preliminary data from the first stage
of the trial showing that single doses of 15 and 45 µg of the vaccine met
seroconversion and seroprotection criteria recommended by U.S. and
European regulatory authorities at 14 days post-dose (see BioCentury,
Dec. 7, 2009 & March 29, 2010).
PolyMedix Inc. (OTCBB:PYMX), Radnor, Pa.
Product: PMX-30063
Molecular target: Not available
Description: Synthetic defensin mimetic bactericidal antibiotic
Indication: Treat bacterial infection
Endpoint: Safety and pharmacokinetics
Status: Phase I data
Milestone: NA
A double-blind, U.S. Phase I trial in 20 healthy volunteers showed that
high-dose IV PMX-30063 was safe when administered for >5 days, with
paraesthesia of the lips, face and fingers reported as the most common side
effects. Additionally, the company said “several” subjects were discontinued by the investigator after 9-13 days of dosing due to increased blood
pressure and heart rate. After 9 days of dosing, there was 1 case of atrial
fibrillation (AF) that was fully reversed within a few hours following
treatment. Patients received an initial IV loading dose of PMX-30063
followed by a daily maintenance dose for up to 14 days. A Phase II trial of
PMX-30063 to treat acute bacterial skin and skin structure infections
(ABSSSI) caused by Staphylococcus aureus is ongoing.
Progenics Pharmaceuticals Inc. (NASDAQ:PGNX), Tarrytown, N.Y.
Product: PSMA ADC
Business: Cancer
Molecular target: Prostate-specific membrane antigen (PSMA) (FOLH1)
(GCPII)
Description: Auristatin-conjugated human mAb against prostate-specific membrane antigen (PSMA)
Indication: Treat metastatic hormone-refractory prostate cancer (HRPC)
Endpoint: Safety; maximum tolerated dose (MTD), pharmacokinetics,
pharmacodynamics and antitumor activity
Status: Preliminary Phase I data
Milestone: NA
See next page
Clinical Results,
from previous page
Preliminary data from an ongoing, open-label, dose-escalation, U.S.
Phase I trial in 21 patients with metastatic HRPC previously treated with
taxane-based chemotherapy regimens showed that 4 doses of 0.4-1.8 mg/
kg IV PSMA ADC every 3 weeks for 12 weeks were well tolerated. The
most common adverse events were fatigue, reversible neutropenia and
elevations in liver enzymes. One patient experienced an acute, fatal case
of pancreatitis that was deemed possibly related to treatment. Additionally, 4 of 9 patients receiving 1.8 mg/kg PSMA ADC showed antitumor
activity as measured by a reduction in prostate specific antigen (PSA) levels,
circulating tumor cells (CTC) counts and/or bone pain. The MTD has not
yet been reached and patients are currently being enrolled in the 2 mg/kg
dose cohort. Data were presented at the American Society of Clinical
Oncology Genitourinary Cancers Symposium in Orlando. PSMA ADC uses
antibody-drug conjugate (ADC) technology from Seattle Genetics Inc.
(NASDAQ:SGEN, Bothell, Wash.).
TransPharma Medical Ltd., Lod, Israel
Product: ViaDor-GLP1 agonist (formerly ViaDerm-GLP1 agonist)
Business: Endocrine
Molecular target: Glucagon-like peptide-1 (GLP-1)
Description: Glucagon-like peptide-1 (GLP-1) agonist delivered using
ViaDor transdermal delivery system
Indication: Treat Type II diabetes
Status: Phase Ib data
Milestone: NA
Data from a 4-way crossover Phase Ib trial in 14 Type II diabetics
showed that single doses of 3 patch formulations of once-daily ViaDorGLP1 agonist were well tolerated, with an extended PK profile compared to that of twice-daily subcutaneous Byetta exenatide. Specifically,
transdermal ViaDor-GLP1 agonist resulted in therapeutic GLP-1 blood
levels for about 20 hours vs. 6 hours for Byetta. Amylin Pharmaceuticals
Inc. (NASDAQ:AMLN, San Diego, Calif.) and Eli Lilly and Co. (NYSE:LLY,
Indianapolis, Ind.) market Byetta.
Verona Pharma plc (LSE:VRP), London, U.K.
Product: RPL554
Molecular target: Phosphodiesterase-3 (PDE-3); Phosphodiesterase-4
(PDE-4)
Description: Long-acting phosphodiesterase-3 (PDE-3) and phosphodiesterase-4 (PDE-4) inhibitor
Indication: Treat mild asthma
Endpoint: Safety and recommended dose
Status: NA data
Milestone: NA
A double-blind, placebo-controlled, Dutch trial in 20 patients with
mild asthma showed that single doses of nebulized RPL554 led to
positive bronchodilation as measured by forced expiratory volume at
1 second (FEV1). RPL554 produced no gastrointestinal symptoms and
there were no withdrawals due to adverse events. The trial evaluated
doses that were 2 and 4 times higher than the highest dose tested in a
previous safety study of the RPL554.
Vertex Pharmaceuticals Inc. (NASDAQ:VRTX), Cambridge, Mass.
Product: VX-770
Business: Pulmonary
Molecular target: Cystic fibrosis transmembrane conductance regulator (CFTR)
Description: Small molecule potentiator of cystic fibrosis transmem-
FEBRUARY 28, 2011
P AGE B17 OF 24
brane conductance regulator (CFTR)
Indication: Treat cystic fibrosis (CF)
Endpoint: Absolute change from baseline in percent predicted forced
expiratory volume in 1 second (FEV1) at week 24; sweat chloride levels,
absolute change from baseline in percent predicted FEV1 at week 48,
Cystic Fibrosis Questionnaire-Revised (CFQ-R), rate of weight change,
time to first pulmonary exacerbation and pharmacokinetics
Milestone: Submit MAA (2H11); submit NDA (2H11); Phase III data
(mid-2011)
The double-blind, international Phase III STRIVE trial in 161
patients ages 12 and up carrying the G551D mutation in CFTR on
at least 1 allele showed that twice-daily 150 mg oral VX-770 met the
primary endpoint of significantly improving the mean absolute
change in FEV1 from baseline to week 24 vs. placebo. Specifically,
the mean absolute improvement in FEV1 at week 24 compared to
placebo was 10.6% (p<0.0001). VX-770 also met the secondary
endpoints of significantly improving the mean absolute change in
FEV1 from baseline to week 48 vs. placebo (10.5%, p<0.0001), and
of a significantly greater proportion of patients that were exacerbation-free at week 48 (67% vs. 41%).
Additionally, patients receiving VX-770 gained an average of 6.8
lbs from baseline to week 48 vs. 0.9 lbs for placebo. Compared to
placebo, VX-770 also led to significant reductions in sweat chloride
levels, which Vertex said are a direct result of defective CFTR
activity in epithelial cells in the sweat duct. Furthermore, patients
receiving VX-770 reported significant improvements in respiratory symptoms on the CFQ-R vs. placebo. The most common
reported serious adverse events were pulmonary exacerbation
and hemoptysis. All patients who completed 48 weeks of treatment
(n=144) were eligible to receive VX-770 in the PERSIST extension
study for up to an additional 96 weeks.
Data from the Phase III ENVISION trial of VX-770 in patients ages
6-11 carrying the G551D mutation in CFTR on at least 1 allele are
expected by mid-2011. Vertex plans to submit regulatory applications
in the U.S. and Europe for VX-770 in 2H11. VX-770 has Fast Track
designation for the indication in the U.S.
Indication: Treat cystic fibrosis (CF)
Endpoint: Safety and absolute change from baseline in forced expiratory
volume in 1 second (FEV1) at week 16; sweat chloride levels, Cystic
Fibrosis Questionnaire-Revised (CFQ-R), rate of weight change and
pharmacokinetics
Status: Phase II data
Milestone: Submit NDA (2H11); submit MAA (2H11); Phase III data
(mid-2011)
The double-blind, U.S. Phase II DISCOVER trial in 140 patients with 2
copies of the delta F508 CFTR mutation showed that twice-daily 150 mg
oral VX-770 missed the co-primary endpoint of significantly improving the
mean absolute change in FEV1 from baseline to week 16 vs. placebo.
Specifically, the mean absolute improvement in FEV1 at week 16 compared
to placebo was 1.6% (p=0.25). On the co-primary safety endpoint, adverse
events that occurred more frequently (≥5%) in the VX-770 arm compared
to placebo were cough, nausea, rash and contact dermatitis, and none of
the events were serious or led to discontinuation of treatment. Additionally, VX-770 significantly reduced mean sweat chloride levels by 2.9 mmol/
L compared to placebo at week 16 (p<0.04).
Data from the Phase III ENVISION trial of VX-770 in patients ages
6-11 carrying the G551D mutation in CFTR on at least 1 allele are
expected by mid-2011. Vertex plans to submit regulatory applications
in the U.S. and Europe for VX-770 in 2H11. VX-770 has Fast Track
designation for the indication in the U.S.
See next page
Clinical News,
from previous page
PRECLINICAL RESULTS
Harbor BioSciences Inc. (OTCBB:HRBR), San Diego, Calif.
Product: Triolex (HE3286)
Business: Neurology
Indication: Treat Parkinson’s disease (PD)
In mice, >50% of levels of Triolex measured in plasma were found
in the brains of mice after oral administration, which indicates that the
compound is capable of crossing the blood-brain barrier (BBB). Triolex,
a synthetic analog of an endogenous adrenal steroid hormone, has
completed Phase IIa testing for Type II diabetes.
Marina Biotech Inc. (NASDAQ:MRNA), Bothell, Wash.
Product: CEQ508
Business: Cancer
Indication: Treat familial adenomatous polyposis (FAP)
In cynomolgus monkeys, daily oral CEQ508 led to no treatmentrelated adverse effects after 281 days of treatment. Additionally, monthly
biopsies of colonic mucosa showed no evidence of local immune activation. The oral RNAi targeting beta-catenin (CTNNB1) delivered using
transKingdom RNAi (tkRNAi) technology is in Phase Ib/IIa testing to treat
FAP, for which it has Orphan Drug designation in the U.S.
Otonomy Inc., San Diego, Calif.
Product: OTO-104
Business: Other
Indication: Treat acute hearing loss
In guinea pigs, single intratympanic injections of OTO-104 provided
significant protection against both noise-induced and cisplatin-induced
hearing loss when administered 24 hours prior to trauma vs. an inactive
control. Additionally, OTO-104 promoted recovery from noise-induced hearing loss when administered 2 days post-trauma. Data were
presented at the Association for Research in Otolaryngology meeting
in Baltimore. The sustained-release dexamethasone gel is in Phase Ib
testing to treat Meniere’s disease, a disorder of the inner ear affecting
balance and hearing.
CLINICAL STATUS
Acacia Pharma Ltd., Cambridge, U.K.
Product: APD421 (formerly ACA1421)
Business: Gastrointestinal
Molecular target: Dopamine D2 receptor
Description: IV formulation of an undisclosed marketed dopamine D2
receptor antagonist
Indication: Prevent cisplatin-induced vomiting
Endpoint: Incidence of vomiting and requirement for anti-emetic rescue
medication during the first 24 hours after dosing with cisplatin
Status: Phase IIa started
Milestone: Phase IIa data (mid-2011); start Phase II (2H11)
Acacia began a Danish and U.K. Phase IIa trial to evaluate single
ascending-doses of APD421 in up to 54 cancer patients. Following the
trial, the company plans to begin a Phase II trial of APD421 to prevent
post-operative nausea and vomiting (PONV).
Active Biotech AB (SSE:ACTI), Lund, Sweden
Product: Tasquinimod (TASQ) (ABR-215050)
Business: Cancer
Molecular target: Thrombospondin-1 (TSP-1) (THBS1)
FEBRUARY 28, 2011
P AGE B18 OF 24
Description: Second generation linomide
Indication: Treat metastatic castration-resistant prostate cancer (CRPC)
Endpoint: Progression-free survival (PFS)
Status: Phase III start
Milestone: Start Phase III (1Q11)
This quarter, Active Biotech will begin a double-blind, placebocontrolled, international Phase III trial to evaluate daily 0.25, 0.5 and 1
mg oral TASQ in about 1,200 patients.
Aestus Therapeutics Inc., North Brunswick, N.J.
Product: ATx08-001 (formerly FK614)
Business: Neurology
Molecular target: Peroxisome proliferation activated receptor (PPAR) gamma
Description: Peroxisome proliferation activated receptor (PPAR)
gamma agonist
Indication: Treat post-herpetic neuralgia (PHN)
Endpoint: Safety and analgesic efficacy
Status: Phase II started
Milestone: Phase II data (10/2011)
Aestus began a double-blind, placebo-controlled Phase II trial to
evaluate low- and high-doses of oral ATx08-001 in about 60 patients.
Aestus has exclusive, worldwide rights to ATx08-001 from Astellas
(see BioCentury, July 5, 2010).
Antares Pharma Inc. (NYSE-A:AIS), Ewing, N.J.
BioSante Pharmaceuticals Inc. (NASDAQ:BPAX), Lincolnshire, Ill.
Product: LibiGel testosterone
Business: Genitourinary
Molecular target: Androgen receptor
Description: Transdermal testosterone gel
Indication: Treat hypoactive sexual desire disorder (HSDD) in menopausal women
Endpoint: Increase in the number of satisfying sexual events and
increase in sexual desire; decrease in sexual distress
Status: Completed Phase III enrollment
Milestone: Complete Phase III enrollment (2011)
BioSante completed enrollment of over 500 surgically menopausal
women in the first of 2 double-blind, placebo-controlled, U.S. and
Canadian Phase III trials evaluating transdermal LibiGel. BioSante
expects to complete enrollment of about 500 patients in the second
Phase III trial this year. The company is also conducting a Phase III safety
trial for the product in 2,869 women and has an SPA from FDA for all
3 trials. In 2000, Antares granted BioSante rights to the product in
North America, Australia, China and certain other countries.
BioCryst Pharmaceuticals Inc. (NASDAQ:BCRX), Birmingham, Ala.
Green Cross Corp., Yongin-Si, South Korea
Shionogi & Co. Ltd. (Tokyo:4507; Osaka:4507), Osaka, Japan
Product: Rapiacta (PeramiFlu) peramivir
Molecular target: Neuraminidase (NEU1) (SIAL1)
Description: Injectable formulation of viral neuraminidase inhibitor
Indication: Treat influenza infection
Endpoint: Time to clinical resolution in a subset of patients not treated
with neuraminidase inhibitors as standard of care; reduction in influenza virus titer as measured by log10 tissue culture infective dose
(TCID50)/mL and by RT-PCR
Status: Phase III amended
Milestone: NA
BioCryst amended the primary efficacy endpoint of the ongoing,
double-blind, placebo-controlled Phase III BCX1812-301 trial to evaluate
See next page
Clinical Status,
from previous page
time to clinical resolution in a subset of about 160 patients not treated with
neuraminidase inhibitors as standard of care. According to the biotech, the
endpoint was changed to provide the best opportunity to show a statistically significant peramivir treatment effect. Total enrollment in the trial
was also increased to up to 600 patients from 445, and the number of
clinical sites was expanded by about 45. The trial was amended as part of
a two-year $55 million contract extension BioCryst received from HHS
to fund the completion of Phase III testing of the influenza candidate. The
extension brings the total amount BioCryst has received from the agency
to $234.8 million. Last month, BioCryst said it was seeking permission and
additional funding from HHS to expand the trial (see BioCentury, Jan. 17).
Peramivir is approved as Rapiacta in Japan. Shionogi has Japanese and
Taiwanese rights to peramivir from BioCryst, while Green Cross has
South Korean rights.
Biomoda Inc. (OTCBB:BMOD), Albuquerque, N.M.
Product: CyPath, Tetrakis Carboxy Phenyl Porphine (TCPP)
Business: Cancer
Molecular target: Undisclosed
Description: Porphyrin-based cytology assay that binds to cancer cells
and fluoresces red under ultraviolet light
Indication: Diagnose early lung cancer
Endpoint: Sensitivity and specificity
Status: Completed Phase II enrollment
Milestone: NA
Biomoda completed enrollment in a single-blind, U.S Phase II trial
of CyPath. In October, the company amended the trial to enroll
additional patients after determining that it did not secure sufficient
samples in the control group (see BioCentury, Oct. 25, 2010). The study
includes a larger cohort of high-risk, heavy military veteran smokers
and a smaller, control cohort of patients already diagnosed with lung
cancer but who have not yet begun treatment.
Eli Lilly and Co. (NYSE:LLY), Indianapolis, Ind.
Merck KGaA (Xetra:MRK), Darmstadt, Germany
Product: Erbitux cetuximab
Business: Cancer
Molecular target: Epidermal growth factor receptor 1 (EGFR1) (HER1)
(ErbB1)
Description: Chimeric IgG1 mAb targeting epidermal growth factor
(EGF) receptor
Indication: Treat advanced or metastatic gastric adenocarcinoma
Endpoint: Progression-free survival (PFS); overall survival (OS), overall
response and quality of life
Milestone: NA
Merck KGaA disclosed in its 4Q10 earnings that it completed
enrollment of 870 patients in the open-label, international Phase III
EXPAND trial evaluating Erbitux in combination with cisplatin and
Xeloda capecitabine. Erbitux is marketed to treat metastatic colorectal
cancer (mCRC) and squamous cell carcinoma of the head and neck
(SCCHN) by ImClone Systems Inc., a subsidiary of Eli Lilly, and BristolMyers Squibb in North America. Merck markets the drug elsewhere,
except in Japan where the 3 companies market the drug. Roche
(SIX:ROG; OTCQX:RHHBY, Basel, Switzerland) markets Xeloda.
Dynavax Technologies Corp. (NASDAQ:DVAX), Berkeley, Calif.
Product: Heplisav (V270)
FEBRUARY 28, 2011
P AGE B19 OF 24
Molecular target: Toll-like receptor 9 (TLR9)
Description: Hepatitis B surface antigen (HBsAg) given with
immunostimulatory DNA sequences (ISS) that target toll-like receptor
9 (TLR9)
Indication: Prevent HBV infection in chronic kidney disease (CKD)
patients
Endpoint: Seroprotection rate at 7 months; safety
Status: Phase III ongoing
Milestone: Submit BLA (year end 2011)
Dynavax said an independent DSMB recommended continuation of
a pair of Phase III trials of Heplisav after reviewing safety data from
patients. In September 2009, the company said FDA lifted a clinical hold
that was in place since March 2008 after a single case of Wegener’s
granulomatosis was observed in the Phase III PHAST trial (see BioCentury,
March 24, 2008). The hold was only lifted for patients with CKD, and
not for healthy adults and children. This is the third review by the DSMB
(see BioCentury, June 7).
DynPort Vaccine Co. LLC, Frederick, Md.
Product: Recombinant botulism vaccine, rBV A/B
Molecular target: Not applicable
Description: Recombinant botulinum neurotoxin serotypes A and B
vaccine
Indication: Prevent botulism
Endpoint: Safety and immunogenicity
Milestone: Phase II data (2012)
DynPort completed enrollment of about 440 healthy volunteers in
a double-blind, placebo-controlled, U.S. Phase II trial evaluating intramuscular 0.5 mL recombinant botulism vaccine on days 0, 28 and 182
or days 0, 56 and 182. The vaccine, which has Fast Track designation
from FDA, is being developed under the agency’s Animal Rule, which
allows marketing approval to be granted based on efficacy in relevant
animal models and an acceptable safety risk profile in humans. DynPort
is developing the vaccine under a U.S. Department of Defense contract.
Global Health Ventures Inc. (OTCBB:GHLV), Vancouver, B.C.
Product: X-Excite (GLV-0902)
Business: Genitourinary
Description: Sublingual formulation of sildenafil citrate
Indication: Treat erectile dysfunction (ED)
Endpoint: Bioavailability and efficacy
Status: Phase I started
Milestone: Phase I data (04/2011)
Global Health began an open-label, European Phase I to compare
X-Excite vs. Viagra sildenafil in 24 patients. Pfizer Inc. (NYSE:PFE, New
York, N.Y.) markets Viagra.
Halozyme Therapeutics Inc. (NASDAQ:HALO), San Diego, Calif.
Product: Subcutaneous rituximab (Subcutaneous MabThera)
Business: Cancer
Molecular target: CD20
Description: Subcutaneous formulation of rituximab, a chimeric mAb
against CD20 antigen
Indication: Treat follicular non-Hodgkin’s lymphoma (NHL)
Endpoint: Overall response rate (ORR) and pharmacokinetics; complete response rates, progression-free survival (PFS), event-free survival, overall survival (OS), immunogenicity and safety
Status: Phase III started
See next page
Clinical Status,
from previous page
Milestone: NA
Roche began an open-label, international Phase III trial to evaluate
1,400 mg subcutaneous MabThera vs. 375 mg/m2 IV Rituxan rituximab
in about 530 patients for 24 weeks. The trial start triggered a $5 million
milestone payment to Halozyme under a 2006 deal to use Halozyme’s
Enhanze recombinant human hyaluronidase (rHuPH20) drug delivery
technology with Roche targets (see BioCentury, Dec. 11, 2006).
Biogen Idec Inc. (NASDAQ:BIIB, Weston, Mass.) and Roche’s
Genentech Inc. unit co-market IV rituximab as Rituxan in the U.S., while
Roche markets it as MabThera elsewhere. In Japan, IV rituximab is comarketed as Rituxan by Chugai Pharmaceutical Co. Ltd. (Tokyo:4519,
Tokyo, Japan), which is majority owned by Roche, and Zenyaku Kogyo
Co. Ltd. (Tokyo, Japan). Further details on the partnership status of
subcutaneous rituximab were not disclosed.
Infinity Pharmaceuticals Inc. (NASDAQ:INFI), Cambridge, Mass.
Mundipharma International Ltd., Cambridge, U.K.
Product: IPI-926
Business: Cancer
Molecular target: Smoothened (SMO)
Description: Hedgehog pathway inhibitor derived from cyclopamine
Indication: Treat pancreatic cancer
Endpoint: Overall survival (OS); progression free survival (PFS), time
to progression and overall response rate (ORR)
Milestone: Phase Ib data (2011)
Infinity began the double-blind, placebo-controlled Phase II portion
of an international Phase Ib/II trial to evaluate oral IPI-926 in combination with Gemzar gemcitabine. The Phase II portion will evaluate oncedaily 160 mg IPI-926, which was the selected dose from the doseescalation Phase Ib portion, in about 120 patients with previously
untreated metastatic pancreatic cancer. Mundipharma partnered with
Infinity to co-develop and commercialize IPI-926 in a 2008 cancer deal.
Infinity has rights to commercialize IPI-926 in the U.S., while Mundipharma
has rights elsewhere (see BioCentury, Nov. 24, 2008). Eli Lilly and Co.
(NYSE:LLY, Indianapolis, Ind.) markets Gemzar.
IQ Therapeutics B.V., Groningen, the Netherlands
Product: Dual Antibody Approach (IQ-DAA)
Molecular target: Bacillus anthracis lethal factor; Bacillus anthracis
protective antigen
Description: Combination of human antibodies against Bacillus anthracis
lethal factor and Bacillus anthracis protective antigen
Indication: Treat inhalation anthrax
Milestone: NA
IQ began a double-blind, placebo-controlled, dose-escalation Phase
I trial to evaluate IQ-DAA in up to 32 healthy volunteers.
KemPharm Inc., North Liberty, Iowa
Product: KP201
Business: Neurology
Description: Hydrocodone combined with a ligand
Indication: Treat pain
Endpoint: Safety; pharmacokinetics
Milestone: NA
FEBRUARY 28, 2011
P AGE B20 OF 24
KemPharm began a crossover Phase I trial to evaluate KP201 in 24
healthy volunteers. Subjects will receive a single dose of 5 mg KP201,
10 mg KP201 and 10/325 mg hydrocodone bitartrate/acetaminophen,
each separated by a 7-day washout period.
Medivir AB (SSE:MVIR B), Huddinge, Sweden
Product: TMC435 (formerly TMC435350)
Molecular target: HCV NS3 protease; Non-structural protein 4A (NS4A)
Description: HCV NS3/4A protease inhibitor
Indication: Treat chronic HCV infection
Endpoint: Proportion of patients with a sustained virologic response
(SVR) after 24 weeks
Milestone: NA
Medivir said Johnson & Johnson’s Tibotec Pharmaceuticals Ltd. unit
began the double-blind, placebo-controlled, international Phase III
QUEST-2 trial in 375 treatment-naïve patients with HCV genotype 1 to
evaluate 150 mg oral TMC435 daily for 12 weeks in combination with
either Pegasys peginterferon alfa-2a and Copegus ribavirin or Pegintron
peginterferon alfa-2b and Rebetol ribavirin. Tibotec has ex-Nordic
rights to develop and commercialize TMC435 from Medivir. Merck &
Co. Inc. (NYSE:MRK, Whitehouse Station, N.J) markets Pegintron and
Rebetol, while Roche (SIX:ROG; OTCQX:RHHBY, Basel, Switzerland)
markets Pegasys and Copegus.
Indication: Treat chronic HCV infection
Endpoint: Proportion of patients with a sustained virologic response
(SVR) after 24 weeks
Milestone: NA
Medivir said Johnson & Johnson’s Tibotec Pharmaceuticals Ltd. unit
began the double-blind, placebo-controlled, international Phase III QUEST1 trial in 375 treatment-naïve patients with HCV genotype 1 to evaluate
150 mg oral TMC435 daily for 12 weeks plus Pegasys peginterferon alfa2a and Copegus ribavirin. Tibotec has ex-Nordic rights to develop and
commercialize TMC435 from Medivir. Roche (SIX:ROG; OTCQX:RHHBY,
Basel, Switzerland) markets Pegasys and Copegus.
Micell Technologies Inc., Raleigh, N.C.
Product: MiStent
Description: Sirolimus-eluting coronary stent system with a
bioabsorbable polymer coating
Indication: Treat coronary artery disease (CAD)
Endpoint: In-stent late lumen loss at 9 months; major adverse cardiac
events (MACE), revascularization rates, stent coverage and reendothelialization via optical coherence tomography (OCT) and endothelial function
Milestone: NA
Micell began the single-blind, international Phase II DESSOLVE II
trial to compare MiStent sirolimus-eluting coronary stent vs. Endeavor
zotarolimus-eluting stent in about 270 patients with stable or unstable
angina pectoris or ischemia. Medtronic Inc. (NYSE:MDT, Minneapolis,
Minn.) markets Endeavor.
Neovacs S.A. (Euronext:ALNEV), Paris, France
Product: IFN-alpha kinoid (IFN-K)
See next page
Clinical Status,
from previous page
Molecular target: Interferon (IFN) alpha
Description: Immunotherapy against interferon (IFN) alpha
Indication: Treat systemic lupus erythematosus (SLE)
Endpoint: Safety; immune response, measures of disease, including
disease activity indices and markers for IFN-alpha activity
Status: Completed Phase I/II enrollment
Milestone: Preliminary Phase I/II data (04/08/2011)
Neovacs completed enrollment of 28 patients in the double-blind,
placebo-controlled, dose-escalation, European Phase I/II IFN-K-001
trial evaluating intramuscular IFN-K over 3 months. Data will be
presented at the European Lupus Meeting in Porto in April.
Grupo Ferrer Internacional S.A., Barcelona, Spain
Product: NCX 1047
Description: Nitric oxide (NO)-donating anti-inflammatory compound
Indication: Treat dermatology disorders
Endpoint: NA
Status: Phase I delayed
Milestone: NA
NicOx disclosed in its 2010 earnings that partner Grupo Ferrer will
delay the start of a Phase I trial evaluating NCX 1047. A timeline for the
trial start, which was delayed for internal reasons, has not been
disclosed. Grupo Ferrer had planned to start the trial early this year.
Oncolytics Biotech Inc. (TSX:ONC; NASDAQ:ONCY), Calgary,
Alberta
Product: Reolysin
Business: Cancer
Molecular target: Not applicable
Description: Formulation of human reovirus type 3
Indication: Treat metastatic colorectal cancer (mCRC) prior to surgical
resection of liver metastases
Endpoint: Presence, replication and anti-cancer effects of reovirus
within liver metastases; anti-tumor activity, safety, and humoral and
cellular immune responses
Status: Completed enrollment
Milestone: data (2011)
Oncolytics completed enrollment of 10 patients in the open-label,
U.K. REO 013 trial evaluating IV Reolysin for 5 consecutive days. Last
year, the company reported data from a histological analysis of 6
evaluable patients treated with Reolysin in the trial showing evidence
of tumor cell death in 4 patients, 2 of which had confirmed K-Ras
mutations in codon 12 (see BioCentury, Nov. 15, 2010).
Onyx Pharmaceuticals Inc. (NASDAQ:ONXX), Emeryville, Calif.
Product: Nexavar sorafenib
Business: Cancer
Molecular target: CRAF (RAF1); Vascular endothelial growth factor
(VEGF) receptor
Description: Inhibitor of RAF1 and multiple receptor tyrosine kinases
Indication: Treat locally advanced or metastatic breast cancer
Endpoint: Progression-free survival (PFS); overall survival (OS), time
to progression, overall response rate (ORR), duration of response and
safety
Milestone: Complete Phase III (08/2012)
FEBRUARY 28, 2011
P AGE B21 OF 24
Bayer and Onyx began the double-blind, placebo-controlled, international Phase III RESILIENCE trial to compare twice-daily oral Nexavar
plus Xeloda capecitabine vs. placebo plus Xeloda in 21-day cycles in 519
patients with locally advanced or metastatic HER2-negative breast
cancer. Nexavar is approved in more than 90 countries to treat liver
cancer and in more than 95 countries to treat advanced kidney cancer.
Bayer and Onyx have a worldwide co-development agreement for
Nexavar outside of Japan, where Bayer owns rights. Roche (SIX:ROG;
OTCQX:RHHBY, Basel, Switzerland) markets Xeloda.
Pharming Group N.V. (Euronext:PHARM), Leiden, the Netherlands
Product: Rhucin (Ruconest - EU) conestat alfa (rhC1INH)
Molecular target: Complement 1 (C1) esterase
Description: Recombinant human complement 1 (C1) esterase inhibitor
Indication: Treat acute attacks of hereditary angioedema (HAE)
Endpoint: Time to beginning of relief based on the visual analog scale
(VAS); minimal important difference (MID) of the overall VAS score,
time to beginning of relief based on MID and on the investigator score,
and safety
Status: Phase IIIb started
Milestone: Complete Phase IIIb (2012)
Pharming began a double-blind, placebo-controlled, international
Phase IIIb trial in 50 HAE patients to evaluate IV Rhucin. Patients
weighing <84 kg and ≥84 kg will receive 50 units/kg and 4,200 units of
Rhucin, respectively. The product is approved as Ruconest in the EU to
treat acute attacks of HAE. Last December, Pharming submitted a BLA
to FDA for Rhucin in the indication. Swedish Orphan Biovitrum AB
(SSE:SOBI, Stockholm, Sweden) has rights to distribute Ruconest in 24
countries in the EU plus Norway, Iceland and Switzerland, while
Santarus Inc. (NASDAQ:SNTS, San Diego, Calif.) has exclusive commercialization rights in North America.
Regeneron Pharmaceuticals Inc. (NASDAQ:REGN), Tarrytown, N.Y.
Product: Rilonacept (Arcalyst) (formerly IL-1 Trap)
Business: Metabolic
Molecular target: Interleukin-1 (IL-1)
Description: Recombinant protein with the heterodimeric IL-1 receptor linked to the Fc portion of human IgG
Indication: Prevent gout flares
Endpoint: Safety; number of gout flares at week 16
Milestone: Phase III data (1Q11)
Regeneron disclosed in its 4Q10 earnings that it completed enrollment of about 1,200 patients taking urate-lowering drugs in the doubleblind, international Phase III RE-SURGE trial evaluating an initial 320 mg
subcutaneous injection of Arcalyst followed by once-weekly 160 mg
Arcalyst.
Indication: Prevent gout flares
Endpoint: Number of gout flares; number of modified gout flares,
proportion of patients with ≥1 gout flare during treatment, proportion
of patients with ≥2 gout flares during treatment, mean number of gout
flares days per patient and mean number of days with pain score ≥5
Milestone: Phase III data (1Q11)
Regeneron disclosed in its 4Q10 earnings that it completed enrollment of about 240 patients in the double-blind, international Phase III
PRE-SURGE 2 trial evaluating subcutaneous Arcalyst when given during
the first 16 weeks of allopurinol therapy. Patients will receive either
an initial 160 mg injection of Arcalyst followed by once-weekly 80 mg
See next page
FEBRUARY 28, 2011
P AGE B22 OF 24
OFFERINGS & SECURITIES TRANSACTIONS
Week ended 2/25/11. Shares after
offering refers to shares outstanding.
Proceeds are gross, not net. Shares
offered don’t include overallotments.
Currency rates used in the week:
C$=US$1.0154; €=$1.3699;
SEK=$0.1563; ¥=$0.012
Completed Offerings
4SC AG (Xetra:VSC), PlaneggMartinsried, Germany
Business: Autoimmune, Cancer
Date completed: 2/24/11
Type: Placing
Raised: €11.7 million ($16.1 million)
Shares: 3.5 million
Price: €3.40
Shares after offering: 42 million
Placement agent: Donner &
Reuschel Privatbank
Acetylon Pharmaceuticals Inc.,
Winchester, Mass.
Business: Cancer, Autoimmune
Type: Venture financing
Raised: $12.4 million
Investors: Not disclosed
Note: Acetylon raised $12.4 million
in a first tranche of a series B round.
Clinical Status,
from previous page
Arcalyst, an initial 320 mg injection of Arcalyst followed by once-weekly
160 mg Arcalyst, or placebo.
Regeneron Pharmaceuticals Inc. (NASDAQ:REGN), Tarrytown,
N.Y.
sanofi-aventis Group (Euronext:SAN; NYSE:SNY), Paris, France
Product: Aflibercept (VEGF Trap)
Business: Cancer
Molecular target: Vascular endothelial growth factor (VEGF); Placental
growth factor (PGF) (PlGF)
Description: Fusion protein containing the extracellular domains from
2 VEGF receptors linked to the Fc portion of human IgG
Indication: First-line treatment of metastatic colorectal cancer (mCRC)
Endpoint: Progression-free survival (PFS) at 12 months; overall response rate (ORR) and overall survival (OS)
Milestone: Interim Phase II data (2H11)
Regeneron disclosed in its 4Q10 earnings that partner sanofiaventis completed enrollment of about 230 patients in the open-label
Phase II AFFIRM trial comparing aflibercept in combination with leucovorin, 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX6) vs. FOLFOX6
alone. The companies are co-developing aflibercept to treat cancer
under a 2003 deal.
Tarix Pharmaceuticals Ltd., Brookline, Mass.
Product: TXA127
Description: Peptide that stimulates early hematopoietic precursor
cells in the bone marrow
Indication: Improve engraftment following autologous peripheral blood
stem cell transplant
Endpoint: Platelet recovery; initial neutrophil recovery
Milestone: Complete Phase II (01/2012)
Tarix began a double-blind, placebo-controlled, U.S. Phase II trial
to evaluate daily 300 µg/kg subcutaneous TXA127 for up to 28 days
following autologous peripheral blood stem cell transplant in 74
patients with Hodgkin’s lymphoma, non-Hodgkin’s lymphoma (NHL)
Biofrontera AG (Xetra:B8F),
Leverkusen, Germany
Type: Private placement
Raised: €1.8 million ($2.5 million)
Shares: 880,000
Price: €2.05
Shares after offering: 10.9 million
Cantargia AB, Lund, Sweden
Business: Cancer
Raised: SEK4.3 million ($638,981)
Investor: Lund University Bio-
science AB
Note: The financing was conducted during 4Q10 and 1Q11.
FluGen Inc., Madison, Wis.
Investors: Knox; and other undisclosed investors
High Throughput Genomics
Inc., Tucson, Ariz
Business: Genomics, Supply/SerSee next page
or multiple myeloma (MM) undergoing limited reinfusion of CD34+
cells. TXA127 has Orphan Drug designation in the U.S. to enhance
engraftment in patients receiving a stem cell transplant and to treat
myelodysplastic syndromes (MDS).
TcLand Expression S.A., Nantes, France
Product: RA-INF-Dx blood test
Description: Multigene molecular diagnostic
Indication: Identify rheumatoid arthritis (RA) patients who are unlikely
to respond to infliximab and methotrexate combination therapy
Endpoint: Performance as measured by the relationship of test result
and non-response according to European League Against Rheumatism
(EULAR) criteria to combination therapy; non-response to combination therapy based on American College of Rheumatology (ACR)
criteria
Status: NA started
Milestone: Market launch (2012)
TcLand began the open-label, European PRINT trial to evaluate the
performance of its RA-INF-Dx blood test in 200 RA patients who are
unlikely to show an initial response to infliximab and methotrexate
combination therapy. Johnson & Johnson (NYSE:JNJ, New Brunswick,
N.J.) and Merck & Co. Inc. (NYSE:MRK, Whitehouse Station, N.J.)
market Remicade infliximab.
Trevena Inc., King of Prussia, Pa.
Product: TRV120027
Molecular target: Angiotensin II type 1 (AT1) receptor (AGTR1)
Description: Dual-acting ligand that inhibits angiotensin-mediated Gprotein signaling and stimulates beta arrestin signaling via the angiotensin II type I (ATI) receptor (AGTR1)
Indication: Treat acute heart failure (AHF)
Endpoint: Safety and pulmonary capillary wedge pressure (PCWP);
effects on hemodynamic parameters, neurohormonal activation and
renal markers
Status: Phase IIa started
Milestone: NA
Trevena began a double-blind, placebo-controlled, dose-ranging
Phase IIa trial to evaluate IV TRV120027 in about 32 patients with stable
heart failure.
FEBRUARY 28, 2011
Completed Offerings,
from previous page
chase 0.913 of a share, with each
whole warrant exercisable at $1.
(Euronext:TIG, Leuven, Belgium),
which is expected to close by June.
vice, Diagnostic
Investors: Novo A/S; Fletcher
Spaght Ventures; Merck Capital
Ventures; Solstice Capital; Valley
Ventures
Note: High Throughput Genomics
raised $15.7 million in a first
tranche of a series D round.
Pharmaron Inc., Irvine, Calif.
Raised: $40 million
Investors: DCM; Legend Capital;
GL Capital Management
Note: The company said it raised
“more than $40 million.”
Cell Therapeutics Inc. (NASDAQ:
CTIC; Milan:CTIC), Seattle, Wash.
Business: Cancer
Date announced: 2/18/11
Type: Private placement of preferred stock
To be raised: Up to $25 million
Shares: 24,957
Price prior: $0.34
Shares outstanding prior: 900.8
million
Investors: Institutional investor
Note: The series 10 preferred
stock bears a 10% dividend. The
investor will also receive twoyear warrants to purchase up to
25.9 million common shares at
$0.34. The investor also has a
right to purchase up to $25 million in convertible series 11 preferred stock. The series 11 stock
converts at $0.34.
ImmunoCellular Therapeutics
Ltd. (OTCBB:IMUC), Woodland
Hills, Calif.
Business: Cancer, Neurology
Type: Private placement of units
Units: 5.2 million
Price: $1.55 (unit)
Placement agents: Summer Street
Research Partners; Dawson James
Securities
Investors: Institutional investors
Note: Each unit comprises a share
and a five-year warrant to purchase 0.5 shares, with each whole
warrant exercisable at $2.25.
Intercell AG (VSE:ICLL; OTCQX:
INRLY), Vienna, Austria
Type: Private placement of senior
notes
Raised: €33 million ($45.2 million)
Underwriter: Erste Bank
Investors: Institutional investors
Note: The unsecured notes bear
6% interest, mature on March 15,
2014, and convert at €11.43.
Palatin Technologies Inc.
(NYSE-A:PTN), Princeton, N.J.
Business: Genitourinary, Cardiovascular, Endocrine
Type: Follow-on
Raised: $23 million
Units: 23 million
Price: $1 (unit)
Underwriters: Roth Capital Partners; Madison Williams and Co.
Note: Each unit consists of a share,
a five-year series A warrant to
purchase 0.087 of a share and a
five-year series B warrant to pur-
SymBio Pharmaceuticals Ltd.,
Tokyo, Japan
Business: Cancer
Raised: ¥2 billion ($24 million)
Investors: Cephalon Inc.; JAFCO
Proposed Offerings
Accentia Biopharmaceuticals
Inc. (OTCQB:ABPI), Tampa, Fla.
Business: Inflammation, Cancer,
Infectious
Type: Best efforts offering
Shares: TBD
Price prior: $0.61
million
Note: The offering is a units financing with each unit consisting
of a share and a five-year warrant
to purchase 0.5 of a share.
Advanced BioHealing Inc.,
Westport, Conn.
Type: IPO
Shares: TBD
Price: TBD
Underwriters: BofA Merrill Lynch;
JPMorgan; Wells Fargo; William
Blair; Oppenheimer
Cellerix S.A., Madrid, Spain
Business: Autoimmune, Dermatology, Gene/Cell therapy
To be raised: Up to €18 milllion
($24.7 million)
Investors: Existing investors
Note: Cellerix plans to raise €18
million ($24.7 million) prior to its
acquisition by TiGenix N.V.
RaQualia Pharma Inc., Aichi, Japan
Business: Infectious, Neurology,
Gastrointestinal
Type: IPO
To be raised: TBD
Shares: 3.7 million
Price: TBD
Underwriter: Daiwa Securities
Capital Markets
Note: The offering is also being
underwritten by 11 other securities firms. RaQualia plans to list
the shares on the JASDAQ Growth
Market of the Osaka Securities
Exchange. The shares are expected
to start trading on March 25.
Theratechnologies Inc. (TSX:
TH), Montreal, Quebec
Business: Endocrine, Pulmonary
Type: Follow-on
To be raised: TBD
Shares: 11 million
Price prior: C$4.81
Underwriters: Jefferies; Stifel
Nicolaus Weisel; RBC Capital
Markets; BMO Capital Markets;
Desjardins; NBF Securities Corp.
Overallotment: 1.7 million
Note: Theratechnologies plans to
sell the shares in an initial listing
on NASDAQ.
TiGenix N.V. (Euronext:TIG),
Leuven, Belgium
P AGE B23 OF 24
Business: Musculoskeletal, Gene/
Cell therapy
Type: Rights offering
To be raised: About €15 million
($20.5 million)
Shares: 15 million
Price: €1
Underwriters: Kempen & Co.;
KBC
million
Investors: Existing investors; institutional investors
Note: TiGenix plans to close the
offering prior to its acquisition of
Cellerix S.A. (Madrid, Spain), which
is expected to close by June.
TiGenix said it already received
commitments for €10 million
($13.7 million) from certain existing and new institutional investors.
Other Financial News
Aeterna Zentaris Inc. (TSX:
AEZ; NASDAQ:AEZS), Quebec
City, Quebec
Business: Endocrine, Infectious,
Cancer
Aeterna established a 2-year,
at-the-market program to sell up
to 12.5 million of its common
stock. McNicoll, Lewis & Vlak is
the sales agent. Aeterna, which
closed Friday at $1.81 has 83.1
million shares outstanding.
Ardea Biosciences Inc.
(NASDAQ:RDEA), San Diego, Calif.
Business: Metabolic, Infectious,
Cancer
Ardea raised $10.7 million
through the sale of 412,500 shares
at $26 to cover overallotments from
its Jan. 20 follow-on, bringing the
total raised to $82.2 million. Ardea,
which closed Friday at $27.09, has
26.5 million shares outstanding.
Chelsea Therapeutics International Ltd. (NASDAQ:CHTP),
Charlotte, N.C.
Business: Cardiovascular, Autoimmune, Neurology
Chelsea Therapeutics raised
$5.3 million through the sale of
1.3 million shares at $4 to cover
See next page
Other Financial News,
from previous page
overallotments from its Feb. 18
follow-on, bringing the total
raised to $40.3 million. Chelsea
Therapeutics, which closed Friday at $4.32, has 61.8 million shares
outstanding.
Genta Inc. (OTCBB:GNTAD),
Berkeley Heights, N.J.
Business: Cancer
Genta implemented a 1-for50 reverse stock split and began
trading under the symbol
“GNTAD.” Following the split,
the company has about 13.3 million shares outstanding.
Osage University Partners,
Bala Cynwyd, Pa.
Business: Finance
Osage University Partners
closed its Osage University Partners I fund at $100 million. The fund
will invest in early- and late-stage
companies in a broad range of sectors, including therapeutics and
medical diagnostics, that have licensed technology from universities affiliated with Osage. The fund
FEBRUARY 28, 2011
has already invested in nine companies, including diagnostics company
Avid Radiopharmaceuticals Inc.,
which Eli Lilly & Co. (NYSE:LLY,
Indianapolis, Ind.) acquired last year.
Paladin Labs Inc. (TSX:PLB),
Montreal, Quebec
Business: Genitourinary, Dermatology, Endocrine
Paladin Labs raised C$5.3 million ($5.3 million) through the
sale of 150,000 shares at C$35 to
cover overallotments from its
Feb. 3 follow-on, bringing the total raised to C$40.3 million ($40.3
P AGE B24 OF 24
million). Paladin, which closed
Friday at C$34.09, has 19.7 million shares outstanding.
Thermo Fisher Scientific Inc.
(NYSE:TMO), Waltham, Mass.
Thermo Fisher said its board
authorized a new, one-year, $750
million share repurchase program.
The company has $385 million
remaining under an existing share
repurchase plan, which expires in
September. Thermo Fisher, which
closed Friday at $55.56, has 390.6
million shares outstanding.

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