SAN DIEGO–(BUSINESS WIRE)–Speaking today at the
4th Immunotherapeutics Immunomonitoring Conference in San
Diego, Dr. Galit Rotman, Chief Scientist of Therapeutics at Compugen
Ltd. (NASDAQ:
CGEN), presented data demonstrating the therapeutic efficacy of
CGEN-15001, CGEN-15021 and CGEN-15091 in animal models of multiple
sclerosis (MS), and the therapeutic efficacy of CGEN-15001 and
CGEN-15021 in animal models of rheumatoid arthritis (RA). CGEN-15001,
CGEN-15021 and CGEN-15091 are predicted B7/CD28-like proteins discovered
using Compugen’s Protein Family Members Discovery Platform.
“These and other previously disclosed
preclinical results for our novel B7/CD28-like proteins, the first
protein family upon which we have chosen to focus our Protein Family
Members Discovery Platform, highlight the potential of this unique
platform, a potential we are only beginning to tap.”
Dr. Rotman reported that in the collagen induced arthritis model of RA,
treatments with either CGEN-15001 or CGEN-15021 in animals with
established disease resulted in dramatic amelioration of clinical
symptoms. Also, both treatments resulted in reduced damage to the
joints, as evidenced by a histological analysis that supports the
disease modifying potential of these treatments. In the experimental
autoimmune encephalitis mouse model of MS, short term treatments with
CGEN-15001, CGEN-15021 or CGEN-15091 all resulted in a long term
dramatic improvement of disease symptoms. Specifically for CGEN-15001,
results demonstrated inhibition of pathological immune responses and of
epitope spreading, which underlie the relapsing remitting nature of the
disease. Overall, these results indicate that CGEN-15001 may prevent
disease progression by immune tolerance induction, a process whereby the
immune system no longer attacks the self-antigens that cause the
disease. Modifying such diseases through immune tolerance induction is a
promising mode of action that may result in effective drugs for
autoimmune diseases.
In her talk, Dr. Rotman presented data demonstrating that the effects of
CGEN-15001 include modulating the activity of a sub-group of white blood
cells called T helper cells, which are known to provide signals for
orchestrating the immune response. CGEN-15001 has been shown to inhibit
the pro-inflammatory T helper cells, Th1 and Th17, while at the same
time promoting anti-inflammatory Th2 responses, a phenomenon known as
Th1/Th2 shift. T cell modulation can be therapeutically beneficial in
the treatment of T cell mediated autoimmune diseases such as MS, RA,
diabetes type 1, psoriasis and others. These encouraging results were
demonstrated both by in vitro and in vivo based test
systems. The research involving CGEN-15001 in MS animal models suggests
that it exerts its beneficial therapeutic effect by modulating the
immune system through the Th1/Th2 shift, inhibiting epitope spreading
and preventing infiltration of reactive immune T cells into the central
nervous system.”
Dr. Rotman concluded, “An efficient treatment for autoimmune diseases
with minimal side effects is a major therapeutic need. Currently, many
of the approved drugs act via global immune suppression, which involves
multiple, potentially serious side effects and expose the body to
opportunistic pathogenic attacks. CGEN-15001, CGEN-15021 and CGEN-15091
offer the opportunity to regulate the immune response in a specific
manner potentially providing significant therapeutic benefits with fewer
side effects.”
Dr. Anat Cohen-Dayag, Compugen’s president and CEO added, “The
CGEN-15001, CGEN-15021 and CGEN-15091 product candidates are based on
three of the nine novel B7/CD28-like proteins predicted and selected in
silico using our Protein Family Members Discovery Platform. This
platform, which utilizes the integration of multiple data sources and
algorithms modeling biological phenomena, was designed to predict and
select unknown members of protein families of high industry interest,
such as the B7/CD28 family. Members of this protein family are important
regulators of the immune system and thus can be targets for treatment of
autoimmune diseases as well as cancer immunotherapy.”
Dr. Cohen-Dayag concluded, “These and other previously disclosed
preclinical results for our novel B7/CD28-like proteins, the first
protein family upon which we have chosen to focus our Protein Family
Members Discovery Platform, highlight the potential of this unique
platform, a potential we are only beginning to tap.”
About CGEN-15001, CGEN-15021, CGEN-15091 and the B7/CD28
protein family
Members of the B7/CD28 protein family have been
intensively studied over the past decade as positive and negative
regulators of the immune response. A growing body of evidence indicates
that dysfunction of immune regulation contributes to the development of
autoimmune diseases.
Positive and negative co-stimulatory pathways play critical roles in
immune regulation and are considered potential targets for modulating
chronic inflammation in autoimmune diseases. To date, one soluble
recombinant fusion protein that selectively blocks the co-stimulatory
signal mediated by the prototype B7/CD28 pathway has been cleared for
marketing in the U.S. for the treatment of moderate to severe rheumatoid
arthritis, and is in clinical trials for other autoimmune indications.
In addition, a number of clinical and preclinical studies for
therapeutic agents targeting these protein families are underway at
various companies.
CGEN-15001 is a novel protein drug candidate consisting of the
extracellular region of CGEN-15001T, a previously unknown membrane
protein predicted by Compugen to be a member of the B7/CD28 family,
fused to a mouse antibody Fc domain. CGEN-15001T was discovered using
Compugen’s Protein Family Members Discovery Platform, and was predicted
to have an immunomodulatory function based on its bioinformatic
characteristics. To date, utilization of this predictive platform by
Compugen has resulted in the discovery of nine proteins predicted to
serve as novel members of this family, including CGEN-15001T and the two
proteins that are the basis of CGEN-15021 and CGEN-15091.
CGEN-15021 and CGEN-15091 are also soluble fusion proteins, each
combining the extracellular domain of one of the new B7/CD28-like proteins
discovered by Compugen, and an Fc antibody fragment. The therapeutic
potential of CGEN-15021 was recently validated in animal disease models
of both multiple sclerosis and rheumatoid arthritis, and that of
CGEN-15091 in an animal disease model of multiple sclerosis. In each of
these disease models, the Compugen fusion proteins demonstrated dramatic
therapeutic effects in ameliorating disease symptoms. In addition, in
earlier in vitro experiments, CGEN-15021 and CGEN-15091 exhibited
inhibition of T cell activation, confirming their predicted role in the
modulation of the immune system.
About Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune
disease that affects the central nervous system, and is caused by
damage to the myelin sheath, the protective covering that surrounds
nerve cells. When this nerve covering is damaged, nerve impulses are
slowed down or stopped. The nerve damage is caused by inflammation,
which occurs when the body’s own immune cells attack the nervous system.
In MS, the immune response is primarily mediated by T cells, that gain
entry into the brain via the blood–brain barrier, but the trigger to
this inflammatory process remains unknown. It is common for the disease
to return (relapse). However, the disease may continue to get worse
without periods of remission. Currently there is no cure for MS, but
several drugs are used for controlling and managing the disease.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a
chronic, systemic inflammatory disorder that affects about 1% of the
world population, and is three times more prevalent in women compared
with men. The disease affects mainly joints, but may also affect other
tissues and organs. Although the cause of rheumatoid arthritis is
unknown, autoimmunity plays a pivotal role in both its chronicity and
progression, and RA is considered a systemic autoimmune disease. RA can
be a disabling and painful condition, which can lead to substantial loss
of functioning and mobility if not adequately treated. Currently
available pharmacological treatments include anti-inflammatory drugs,
such as steroids and disease-modifying anti-rheumatic drugs (DMARDs).
Due to side effects associated with current therapies, efforts are being
made to develop a newer group of biologics to increase treatment options.
About Compugen
Compugen 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, either for Compugen or its partners. Unlike traditional
high throughput trial and error experimental based drug candidate
discovery, Compugen’s discovery efforts are based on systematic and
continuously improving in silico (by computer) product candidate
prediction and selection followed by experimental validation, with
selected product candidates being advanced in its Pipeline Program to
the pre-IND stage. Compugen’s in silico predictive models utilize
a broad and continuously growing infrastructure of proprietary
scientific understandings and predictive platforms, algorithms, machine
learning systems and other computational biology capabilities. The
Company’s business model primarily involves collaborations covering the
further development and commercialization of Compugen-discovered product
candidates and various forms of “discovery on demand” arrangements, in
both cases providing Compugen with potential milestone payments and
royalties on product sales or other forms of revenue sharing. 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”, “anticipates”,
“believes”, and “intends”, and describe opinions about future events.
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; the impact of competitive products and
technological changes; risks relating to the development of new
products; and the ability to implement technological improvements. 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,
2010 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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