Compugen Ltd. (NASDAQ: CGEN), announced today the discovery and
initial validation of two new drug target candidates for monoclonal
antibody (mAb) cancer therapy. These new candidates have been shown
to be expressed in multiple types of tumors and were shown to have
an immunomodulatory activity in affecting both innate and adaptive
immune responses, thus providing the potential for an efficient and
targeted approach in cancer treatment. By offering a different mode
of action from Compugen's other immune checkpoint candidates, these
molecules further broaden the scope of the Company's Pipeline
Program for monoclonal antibody treatment of cancer.
In recent in vitro studies, both of these immune checkpoint
molecules have shown distinct activity inhibiting two key subtypes
of immune cells, Natural Killer (NK) cells and T cells. These key
immune cell subtypes act to recognize and kill tumor cells and have
critical roles in the response of the immune system to tumor
development. Antibodies directed against and blocking each of these
immune checkpoints could remove their inhibitory effect on T cells
and NK cells, thus enhancing the anti-tumor activity of these
pivotal immune cell subsets. Therefore, agents targeting these
checkpoint molecules hold great promise for efficient cancer
immunotherapy and long-lived tumor destruction.
Recent protein expression studies for these two
Compugen-discovered molecules indicate enhanced expression in a
wide variety of cancers with high unmet medical need. These include
lung, ovarian, breast, colorectal, gastric and liver cancer. Hence,
in addition to their potential utility in cancer immunotherapy,
which aims to stimulate the patient’s own immune system to
eliminate cancer cells, these two molecules also have therapeutic
potential as drug targets for direct cancer mAb therapy, whereby
monoclonal antibodies directed against these targets would directly
destroy the cancer cells.
Dr. Anat Cohen-Dayag, President and CEO of Compugen, stated, “It
is increasingly evident that the blockade of immune checkpoints is
among the most promising approaches to activate therapeutic
anti-tumor immunity. Therefore, we are very pleased with the
addition of the two immune checkpoint targets being disclosed
today, each of which acts on both arms of the immune system."
Dr. Cohen-Dayag continued, "These two molecules broaden
Compugen's oncology pipeline, thus potentially providing
differentiated and effective solutions for multiple forms of
cancer. In this respect, we recently reported that CGEN-15001, an
Fc fusion protein based on the Compugen-discovered CGEN-15001T
immune checkpoint target, promotes inducible regulatory T cells
(iTregs) in addition to its inhibitory effect on T cells.
Therefore, an antibody directed against and blocking CGEN-15001T
has the potential to eliminate the inhibitory effect of this
molecule on T cells and, in parallel, to inhibit iTregs'
pro-tumorigenic effects. Given the current scientific understanding
that multiple modes of action will be required for effective cancer
treatments, our pipeline now includes a number of distinct oncology
product candidates, including the two being disclosed today,
further attesting to the predictive strength of our in silico
approach to drug discovery."
About Immune Cells, Checkpoint Proteins and CancerNatural
Killer cells, T cells, and iTregs, are key immune cells in the
innate and adaptive immune responses, and all are modulated by
immune checkpoint proteins. The innate immune response provides the
body with a general first line of defense against pathogens, while
the adaptive immune response endows the immune system with
long-lasting and protective memory in preparation for future
assaults by the same antigen.
NK cells are the front line troops of the innate immune system,
constantly on patrol for pathogens or tumor cells. NK cells aim to
recognize and kill tumor cells, and as such have become a subject
of intensive investigation in the field of tumor immunology. NK
cell-mediated killing of tumor cells depends on the balance between
stimulatory and inhibitory pathways. Thus, antibody blockade of NK
inhibitory pathways is a promising strategy to enhance NK cell
activity and is an emerging treatment modality for cancer
immunotherapy.
T cells are major players in the potent adaptive immune response
to detect and destroy tumor cells. However, negative costimulatory
immune checkpoint proteins expressed by the cancer cells often are
responsible for the suppression of the anti-tumor activity of these
T cells. As such, T-cell based immunotherapy, which aims to
initiate or augment T cell responses against tumor cells, is an
attractive new approach in cancer treatment.
iTregs are immunosuppressive cells accumulating in the tumor
microenvironment and in the circulation of patients with cancer,
and are responsible for the suppression of the anti-tumor capacity
of the immune system. Tumor progression thus benefits from the
immunosuppressive effects mediated by iTregs. Inhibition of these
cells is also considered one of the most promising approaches for
cancer treatment, as it would enhance anti-tumor immunity and
increase the efficacy of cancer immunotherapy.
Tumors develop specific immune resistance mechanisms. An
important immune resistance mechanism involves immune-inhibitory
pathways, termed immune checkpoints, which are expressed on immune
cells, mainly activated by T cells and iTregs, and also NK cells.
Clinical studies employing mAb blockade of immune checkpoints, such
as PD-1 and CTLA4, have shown unprecedented durable responses and a
possible cure of metastatic disease. Antibodies targeting immune
checkpoints have been thus termed “the next frontier" in the
treatment of cancer.
About CompugenCompugen is a leading therapeutic product
discovery company focused on therapeutic proteins and monoclonal
antibodies to address important unmet needs in the fields of
immunology and oncology. Unlike traditional high throughput trial
and error experimental based discovery, Compugen utilizes a broad
and continuously growing integrated infrastructure of proprietary
scientific understandings and predictive platforms, algorithms,
machine learning systems and other computational biology
capabilities for the in silico (by computer) prediction and
selection of product candidates, which are then advanced in its
Pipeline Program to the pre-IND stage. The Company's business model
primarily involves collaborations covering the further development
and commercialization of product candidates from its Pipeline
Program and various forms of research and discovery agreements, in
both cases providing Compugen with potential milestone payments and
royalties on product sales or other forms of revenue sharing. In
2012, Compugen established operations in California for the
development of oncology and immunology monoclonal antibody
therapeutic candidates against Compugen-discovered drug targets. In
2002, Compugen established an affiliate, Evogene Ltd.,
(www.evogene.com) (TASE: EVGN.TA), to utilize certain of the
Company's in silico predictive discovery capabilities in
agricultural biotechnology. For additional information, please
visit Compugen's corporate website at www.cgen.com.
This press release may contain “forward-looking statements”
within the meaning of the Private Securities Litigation Reform Act
of 1995. These statements include words such as “may,” “expects,”
“projects,” “anticipates,” “believes” and “intends,” and describe
opinions about future events. Forward-looking statements in this
press release include, but are not limited to, that agents
targeting the two Compugen-discovered checkpoint molecules hold
great promise for efficient and long-lived tumor destruction, that
these two molecules also have therapeutic potential as drug targets
for direct cancer mAb therapy, and that an antibody directed
against and blocking CGEN-15001T has the potential to eliminate the
inhibitory effect of this molecule on T cells and, in parallel, to
inhibit iTregs pro-tumorigenic effects. 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. Some of these risks are: changes in
relationships with collaborators, including, without limitation,
corporate partners or licensees; the impact of competitive products
and technological changes; risks relating to the development of new
products in general; risks relating to the research, development,
regulatory approval, manufacturing or marketing of new therapeutic
or diagnostic products; the ability to implement technological
improvements; and risks related to obtaining necessary resources,
including, without limitation, capital. These and other factors are
discussed in the "Risk Factors" section of Compugen’s Annual Report
on Form 20-F for the year ended December 31, 2011 as filed 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.
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