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Genentech reaches for the stars
March 2012
![]() SHARING OPTIONS:
CAMBRIDGE, Mass.—Gazing eastward toward the
night sky,
Genentech, a member of the Roche Group, has hitched its wagon to a star called
Constellation Pharmaceuticals Inc., forging a major strategic
agreement aimed
at developing cancer treatments based on Constellation's epigenetics expertise.
For this acumen, California-based Genentech has agreed to
pay an unspecified upfront payment and $95 million in research funding over the
course
of three years. Constellation could also receive substantial milestone
payments based on development and commercialization goals, as well as double-digit
royalties on any commercial sales of products by Genentech that come from the
agreement.
Epigenetics is the study of certain types of proteins that
affect chemical modifications on specific sites on DNA or chromosomal proteins.
A key
to the reading of these genetic changes is the substance chromatin, which
is also a target of the research in the collaboration, the companies stated in
a Jan. 17 news release.
Epigenetics research focuses on changes in gene expression
that can be
passed on to the next generation, but do not change underlying gene
sequences. Chromatin is the combination of DNA and proteins in the nucleus of a
cell.
The agreement also calls for the companies to establish a
research collaboration
addressing multiple epigenetic target classes.
Constellation will retain independent strategic direction, operational
management and exclusive rights
to programs outside of the collaboration scope,
including its two most advanced programs that are focused on the development of
inhibitors of the BET
chromatin reader and EZH2 chromatin writer proteins.
Genentech has a future option to acquire all
outstanding
shares of Constellation based on pre-negotiated terms, which include a
significant initial acquisition payment plus contingent value rights
payments
based on the future successful development and commercialization of multiple
products by Genentech. Genentech's option to acquire
Constellation includes the
BET and EZH2 programs as well as other programs outside the collaboration
scope.
"Genentech is a global leader in the research and
development of innovative medicines, and in combination with our class-leading
product
engine and deep expertise in chromatin biology, will create a
powerhouse dedicated to bringing the greatest benefit to patients from drugs
that
modulate epigenetic pathways," states Dr. Mark A. Goldsmith, president and
CEO of Constellation Pharmaceuticals. "This is a groundbreaking partnership
in
terms of the structure, breadth and potential future clinical impact of
products created through our complementary capabilities. The committed
revenue
and post-collaboration economics should provide a highly attractive return for
our investors."
Dr. James Sabry, vice president of Genentech Partnering,
adds, "We believe Constellation is a leading company in chromatin
biology and
epigenetics drug discovery and an excellent partner for Genentech in this area.
With scientists committed to the collaboration at both
Constellation and
Genentech working together in a highly integrated way, our goal is to discover
and ultimately bring to market promising new therapies
for patients with unmet
medical needs in oncology, and potentially other therapeutic areas."
Sabry tells ddn that
the deal "is one of the largest research collaborations we have done, and speaks
to our interest in continuing to
build first-in-class cancer drugs that will
deliver true clinical value to patients, specifically in the rapidly evolving area
of epigenetics and
cancer."
As it turns out, Constellation was never far from
Genentech's radar.
"We were both well aware of each other from the moment
Constellation was formed," Sabry says. "We had been
communicating for years
prior to the collaboration being signed, and when the time was optimal for both
companies, we moved ahead effectively to
structure, negotiate and close the
deal."
Why epigenetics as opposed to more traditional
modalities of
researching and treating cancer?
"Epigenetics describes a body of scientific
mechanisms,
targets and pathways that are involved in basic developmental and cellular
biology," Sabry says. "Recently, a connection of this basic
biology to the
pathophysiology of cancer has been made by many laboratories. We believe that
drugs that modulate epigenetic pathways may represent
novel and highly
effective therapies for a wide variety of cancers. This is one of a handful of
promising new areas for the treatment of cancer."
Drug development in the field of epigenetics is directed
towards the identification of small molecules
that inhibit the activities of
proteins that add, remove or recognize various chemical modifications to
specific sites on DNA or chromosomal
proteins. These marks play a key role in determining whether a gene is
on or off. Epigenetic regulators are often referred to as writers, erasers
and
readers. Research at Constellation and by others has shown that abnormal
epigenetic regulation contributes to many different diseases.
In a study of chromatin readers that appeared recently in
the Proceedings of the National Academy of Sciences, Constellation scientists demonstrated that
transcription of the MYC oncogene can be suppressed using small-molecule
inhibitors of the BET family of chromatin adapters. MYC is a master
regulator
of diverse cellular functions and has long been considered a compelling therapeutic
target because of its role in many human malignancies
including hematologic and
solid tumors. Also, continued research by Constellation on chromatin modifying
enzymes has resulted in significant progress
towards developing small molecule
inhibitors of the histone lysine methyltransferase EZH2. This enzyme functions
as part of a chromatin-associated
protein complex implicated in the repression
of gene expression.
Recent cancer genomic sequencing
studies have identified
recurrent mutations in the EZH2 encoding genomic locus in a subset of human
cancers. In addition, numerous epidemiological data
sets linking increased EZH2
expression to late stage disease with poor prognosis suggest a prominent role
for EZH2 in human malignancies.
Sabry declines to speculate on the specific types of cancer
to be addressed.
"Our goal is to … deliver meaningful clinical value to
patients with a wide variety of cancer," Sabry says. "We have
already begun our
research collaboration and our scientists are working closely with colleagues
at Constellation to identify promising new approaches
and drug candidates in
the field of epigenetics." Code: E031217 Back |
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