Compugen Announces Positive Therapeutic Effects of Novel Peptide in Animal Model of Inflammatory Bowel Disease
23 Junio 2009 - 6:00AM
Business Wire
Compugen Ltd. (NASDAQ:CGEN) announced today that CGEN-25007, a
novel peptide antagonist of gp96 with potent anti-inflammatory
activity, has shown positive therapeutic effects in an animal model
of inflammatory bowel disease (IBD), a commonly used term covering
ulcerative colitis and Crohn's disease.
CGEN-25007 was initially discovered using Compugen�s
Disease-Associated Conformation (DAC) blockers discovery platform.
This platform was designed for the systematic discovery of novel
peptides that block proteins of interest from achieving certain
disease-associated conformations, a capability that represents
immense therapeutic promise in numerous fields. The platform is
based on the integration of methods and ideas varying from
information theory, through machine learning and statistics, to
mathematical analysis for detecting intra-molecular interactions
within the protein of interest.
In a recently completed study of TNBS-induced colitis, which is
a well accepted animal model of inflammatory bowel disease,
administration of CGEN-25007 protected mice from the effects of
lethal colitis. Study data showed an increase in survival rate and
reversal of weight loss, while mice treated with a negative control
showed an irreversible and fatal wasting syndrome. This protective
effect of CGEN-25007 was confirmed by improved endoscopic colitis
scores, which were similar to those obtained with corticosteroids
as a positive control. These results suggest that CGEN-25007 could
have a potential therapeutic utility to treat IBD and other
autoimmune diseases with a strong inflammatory component, such as
rheumatoid arthritis.
Professor Markus F. Neurath, from the University of Erlangen,
Germany, who supervised the study and is a recognized world expert
in this field, stated, �The results achieved with CGEN- 25007 are
very impressive. In the past, we have evaluated numerous molecules
in this model but never saw such dramatic effects. If these results
continue to be confirmed in further studies, this molecule should
represent a very exciting drug candidate for this substantial, and
largely unmet medical need."
Compugen�s discovery of CGEN-25007 through the use of its DAC
Blockers Platform was first announced last year following the
successful completion of various initial in vitro and in vivo
validation studies for acute inflammation. The very high levels of
anti-inflammatory activity observed in these earlier acute studies
led to the decision by Compugen to also evaluate CGEN-25007 for
application in chronic inflammatory conditions.
Dr. Anat Cohen-Dayag, co-CEO at Compugen, said, �We are
extremely pleased by the continuing validation of the potent
anti-inflammatory activity of CGEN-25007. The excellent results
seen in this well accepted disease model for inflammatory bowel
disease further support the therapeutic application of this
molecule in a number of important medical conditions. Of equal
importance is the continuing validation of our unique DAC Blockers
Platform.�
About IBD
Inflammatory bowel disease is a chronic, relapsing and remitting
inflammatory condition, affecting around two million people in the
seven major markets (2007). Due to rising disease rates and
evolving diagnostic methods, the market for intestinal
anti-inflammatories and IBD drugs is forecasted to continue
expanding. The condition is believed to result from the aggregate
effect of genetic variations conferring risk of disease and
environmental factors affecting the immune system, which combined,
lead to an aberrant inflammatory response. In the US, IBD is one of
the most prevalent gastrointestinal disease burdens. Currently,
this chronic condition is without a medical cure and commonly
requires a lifetime of care.
About gp96
The gp96 protein triggers both the innate and adaptive arms of
the immune system and its importance in inflammatory responses has
been demonstrated in recent years. gp96 plays an important role in
the activation of innate immunity through direct action on various
types of immune cells and by promoting the induction of
pro-inflammatory cytokines. Moreover, gp96 is essential for
Toll-like receptors (TLRs); and, its interaction with ligands of
such TLRs amplifies immune responses. Recent findings point to gp96
as a valid target for therapeutic intervention in the treatment of
immune-related disorders, such as rheumatoid arthritis and
inflammatory bowel disease.
About the DAC Blockers
Discovery Platform
Compugen�s Blockers of Disease-Associated Conformation (DAC
Blockers) platform was first disclosed in March 2008, and is one of
ten product candidate discovery platforms validated to date by the
Company. The DAC Blockers Platform is designed for the prediction
and selection of peptides that block proteins from adopting their
disease-associated conformations. This is accomplished through the
use of a series of proprietary algorithms to identify segments in
proteins of interest that, if introduced as synthetic peptides,
would prevent the proteins from adopting disease-associated
conformations and related activities and thus could have
therapeutic benefits. In addition, a key capability of the platform
is that the prediction and selection capability enables
proteome-wide searches for such peptides in proteins of interest
within human, viral and bacterial proteomes. To date, peptide
blockers predicted by this platform have been validated
experimentally in functional assays for 11 out of 12 protein
targets selected for screening. Of these 11 peptides, in addition
to CGEN-25007, two others have demonstrated therapeutic potential.
Additional peptides targeting other important protein targets are
now undergoing experimental validation.
About Compugen
Compugen is a leading drug and diagnostic product candidate
discovery company. Unlike traditional high throughput trial and
error experimental based discovery, Compugen�s discovery efforts
are based on in-silico (by computer) prediction and selection
utilizing a growing number of field focused proprietary discovery
platforms accurately modeling biological processes at the molecular
level. The resulting product candidates are then validated through
in vitro and in vivo experimental studies and out-licensed for
further development and commercialization under various forms of
revenue sharing agreements. Compugen�s current collaborations
include Biosite, Medarex, Inc., Merck & Co., Inc., Merck
Serono, Ortho-Clinical Diagnostics (a Johnson & Johnson
company), Roche, Siemens Healthcare Diagnostics, Inc., and Teva
Pharmaceutical Industries. 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 Web site 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
identified and more fully explained under the heading "Risk
Factors" in Compugen's annual reports filed with the Securities and
Exchange Commission.
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