Compugen Announces Initial Validation Results for Two Novel Immunomodulatory Proteins and Further Results for CGEN-15001
- Category: Proteins and Peptides
- Published on Tuesday, 24 April 2012 18:29
- Hits: 249
- CGEN-15031 and CGEN-15051 demonstrate therapeutic potential in animal models of autoimmune diseases
- Further results substantiate CGEN-15001's immunomodulatory activity and potential for additional utility in the treatment of inflammatory bowel diseases
TEL AVIV, Israel I April 24, 2012 I Compugen Ltd. (NASDAQ: CGEN - News) today reported the initial validation of two additional therapeutic product candidates, CGEN-15031 and CGEN-15051, in animal models of autoimmune diseases. These two novel molecules are soluble proteins based on two B7/CD28-like proteins discovered by Compugen, with each fusion protein combining the extracellular domain of one of the membrane proteins and an Fc antibody fragment. The results being announced today relate to the recently completed evaluation of the potential therapeutic activity of CGEN-15031 in an animal disease model of multiple sclerosis and of CGEN-15051 in a model of rheumatoid arthritis. The Compugen fusion proteins significantly ameliorated disease symptoms in these models and are predicted to have a potential use as protein therapeutics for multiple autoimmune diseases. The study of CGEN-15031 in the EAE model of multiple sclerosis was carried out in the laboratory of Prof. Stephen Miller at Northwestern University. CGEN-15051 was tested using the CIA model of rheumatoid arthritis at a commercial lab specializing in animal models of autoimmune diseases.
Compugen also announced today that results from additional studies relating to CGEN-15001, the first of the Compugen-discovered B7/CD28-like based fusion proteins to undergo experimental validation, continue to support its immunomodulatory role and potential use in the treatment of multiple autoimmune diseases. Using an adoptive transfer EAE model, administration of CGEN-15001 to mice with established disease induced by transfer of CNS-autoaggressive immune cells, displayed robust inhibition of disease symptoms and abolishment of further relapses. Moreover, amelioration of disease symptoms was accompanied by up-regulation of the anti-inflammatory cytokines, IL-10 and IL-4, and potent reduction in the secretion of pro-inflammatory cytokines.
Furthermore, CGEN-15001T, the membrane protein that CGEN-15001 is based on, was recently shown to be expressed in samples from the gastrointestinal tracts of patients diagnosed with Crohn's disease and ulcerative colitis, the two major types of inflammatory bowel disease. CGEN-15001T was shown to be specifically over expressed on both the epithelium and immune cells in diseased tissues, compared with the respective normal tissues. These findings further support CGEN-15001's immunomodulatory role and indicate CGEN-15001’s additional potential utility in the treatment of these inflammatory bowel diseases, which also represents a major unmet medical need for new, more effective therapies.
Dr. Anat Cohen-Dayag, President and CEO of Compugen Ltd., stated, "We are extremely encouraged by the progress of our therapeutic protein product candidates, which comprise one of the two arms of our Pipeline Program, with the second being monoclonal antibody therapeutics. Our therapeutic protein candidates, at present primarily fusion proteins based on Compugen-discovered B7/CD28-like membrane molecules, continue to demonstrate significant therapeutic potential for a large number of unmet medical needs in the fields of immunology."
Dr. Cohen-Dayag continued, “In addition to demonstrating areas of potential superiority for our novel product candidates compared with products in the market or under development by others, Compugen is currently undertaking significant efforts to differentiate between our multiple immunomodulatory product candidates in terms of their modes of action, and the specific medical condition which each of them should target. These differentiation activities are required in order to maximize the medical and commercial value of our unique ability to discover multiple product candidates for clinical unmet needs.”
About novel CGEN immunomodulators 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 have B7/CD28-like characteristics, fused to an antibody Fc domain. CGEN-15001T was discovered using Compugen's Protein Family Members Discovery Platform, and was predicted to have an immunomodulatory function using an algorithm-based determination and identification of previously unknown family characteristics. CGEN-15001 was the first protein drug candidate from this discovery platform validated experimentally by Compugen in animal models of autoimmune diseases. To date, utilization of this discovery platform by Compugen has resulted in the prediction of nine membrane B7/CD28-like proteins, which include CGEN-15001T and four additional membrane proteins that are the basis of the soluble fusion proteins CGEN-15021, CGEN-15031, CGEN-15051 and CGEN-15091.
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 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 drug candidates against Compugen-discovered 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 http://www.cgen.com.