HOLON, Israel, November 11, 2016 /PRNewswire/ --
Compugen Ltd. (NASDAQ: CGEN), a leading predictive drug
discovery company, today presented new data for its preclinical
CGEN-15029 program demonstrating the potential for the development
of new cancer immunotherapy treatments for solid tumors, including
the potential for drug combination with current immune checkpoint
blockers. CGEN-15029 is the internal designation for PVRIG, a novel
immune checkpoint identified by Compugen utilizing its in
silico predictive discovery infrastructure. The Company plans
to file an IND in 2017 for COM701, its lead antibody targeting
PVRIG.
Today's presentation, titled "Computational identification,
functional characterization and antibody blockade of a new immune
checkpoint in the TIGIT family of interacting molecules" was made
by John Hunter, Ph.D., Site Head and
Vice President, Antibody R&D, Compugen USA, Inc. The presentation included the
discovery by Compugen of PVRIG and its expression pattern in the
context of cancer, demonstrating that PVRIG is expressed in
infiltrating immune cells in solid tumors, specifically on cells
with potent anti-tumor activity, such as effector T-cells and
natural killer cells. Also disclosed was the identification of
PVRL2 as PVRIG's ligand, and the functional characterization and
anti-tumor in vitro and in vivo efficacy of blocking
antibodies developed by Compugen targeting the interaction of PVRIG
with PVRL2. Binding of PVRIG to PVRL2 is of particular therapeutic
interest, as it links PVRIG to the axis of a second immune
checkpoint, TIGIT, which is recently gaining traction in the field
of immuno-oncology.
In his presentation, Dr. Hunter presented additional data
demonstrating that antibodies developed by Compugen, which block
the interaction between PVRIG and PVRL2, enhance activation of the
immune system by activating both primary CD4+ T-cells and
tumor-derived CD8+ T-cells.
Consistent with the placement of PVRIG in the TIGIT axis,
antibody blockade of both TIGIT and PVRIG had an additive effect on
human T-cell stimulation, indicating the potential of the two to
generate enhanced immune response against the cancer. Moreover,
antibodies targeting the mouse PVRIG developed by the Company were
assessed in vivo for effects on tumor growth inhibition in
mouse models, commonly used to study immune checkpoint inhibitors.
In these studies, antibodies that block the mouse PVRIG/PVRL2
interaction, similar to those generated against the human target,
were shown to inhibit tumor growth when used in combination with
PD1 pathway blockade. These results were further reinforced when
tumor growth was tested in knock-out (KO) mice. Tumor growth was
significantly reduced in KO mice, where the PVRIG gene was removed.
Consistent with the antibody combination data, this effect was even
further enhanced in the KO mice when they were treated with
anti-PDL1 blocking antibodies.
Collectively, the experimental data strongly suggest that PVRIG,
which was initially predicted computationally by the Company to
serve as a novel immune checkpoint target, presents a new
opportunity for the development of cancer immunotherapy treatments,
including the potential for drug combination with current immune
checkpoint blockers.
In June 2016, the Company selected
COM701, a high affinity antagonist antibody against PVRIG, as the
lead therapeutic candidate for the program. COM701, which is
currently in preclinical development by the Company, demonstrates
potent and reproducible enhancement of T-cell activation,
consistent with the desired mechanism-of-action required to
generate anti-tumor immune responses.
Anat Cohen-Dayag,
Ph.D., CEO and President of Compugen, explained,
"While antibody blockade of the CTLA4 and PD1 pathways has emerged
as an effective treatment modality for certain types of cancer, the
majority of patients do not derive long-term benefits, suggesting a
need for additional approaches such as new immune checkpoints
targeting new pathways and providing new mechanisms to activate the
immune response against the tumor. Employing our unique predictive
infrastructure to define new immune checkpoint targets, we
identified PVRIG, among other novel immune checkpoint target
candidates in our target pipeline."
Dr. Cohen-Dayag continued, "We are very pleased to
see the rapidly increasing amount of preclinical data demonstrating
the potential utility of COM701, an antibody targeting PVRIG, as a
new cancer immunotherapy treatment. These results highlight, once
more, the power and uniqueness of our computational predictive
approach - from computer prediction of novel drug targets to
preclinical validation. This capability, along with our
significantly enhanced development infrastructure, allows us now to
pursue and advance a number of novel immuno-oncology programs with
potentially different mechanisms-of-action, thus providing us with
a diversified early-stage internal target pipeline, in addition to
the two programs that are the subject of an ongoing pharma
collaboration."
About PVRIG
PVRIG (designated internally as CGEN-15029) is one of the novel
B7/CD28-like immune checkpoint target candidates discovered by
Compugen utilizing its predictive discovery infrastructure. The
CGEN-15029 target was predicted in silico and experimentally
confirmed to be a receptor-like immune checkpoint protein expressed
on immune cells. In June 2016,
COM701, a high affinity antagonist antibody against CGEN-15029, was
selected as the lead therapeutic candidate for the program.
About Compugen
Compugen is a leading therapeutic discovery company utilizing
its broadly applicable predictive discovery infrastructure to
identify novel drug targets and develop first-in-class biologics.
The primary focus of the Company's current pipeline is on immune
checkpoint target candidates discovered by the Company, potentially
providing the basis for a next wave of therapeutics for cancer
immunotherapy. Compugen's business model is based on selectively
entering into collaborations for its novel target candidates and
drug product candidates at various stages of research and
development under revenue-sharing agreements. The Company is
headquartered in Israel, with
R&D facilities in Israel and
South San Francisco. At the US facilities, monoclonal antibody
therapeutic candidates are discovered and developed against the
Company's novel target candidates. For additional information,
please visit Compugen's corporate website at
http://www.cgen.com.
Forward-Looking Statement
This press release contains "forward-looking statements" within
the meaning of the Private Securities Litigation Reform Act of
1995. Forward-looking statements can be identified by the use of
terminology such as "will," "may," "expects," "anticipates,"
"believes," and "intends," and describe opinions about future
events, and include statements relating to the potential of the
CGEN-15029 program for the development of new cancer immunotherapy
treatments for solid tumors, including the potential for drug
combination with current immune checkpoint blockers and the
potential of COM701 as a new cancer immunotherapy treatment. These
forward-looking statements involve known and unknown risks and
uncertainties that may cause the actual results, performance or
achievements of Compugen to be materially different from any future
results, performance or achievements expressed or implied by such
forward-looking statements. Among these risks: Compugen's business
model is substantially dependent on entering into collaboration
agreements with third parties, and Compugen may not be successful
in generating adequate revenues or commercializing aspects of its
business model. Moreover, the development and commercialization of
therapeutic candidates involve many inherent risks, including
failure to progress to clinical trials or, if they progress to or
enter clinical trials, failure to receive regulatory approval.
These and other factors are more fully discussed in the "Risk
Factors" section of Compugen's most recent Annual Report on Form
20-F as filed with the Securities and Exchange Commission as well
as other documents that may be subsequently filed by Compugen from
time to time with the Securities and Exchange Commission. In
addition, any forward-looking statements represent Compugen's views
only as of the date of this release and should not be relied upon
as representing its views as of any subsequent date. Compugen does
not assume any obligation to update any forward-looking statements
unless required by law.
Company contact:
Tsipi Haitovsky
Global Media Liaison
Compugen Ltd.
Email: tsipih@cgen.com
Tel: +972-52-598-9892
SOURCE Compugen Ltd.