Compugen Ltd announced the discovery and experimental validation of CGEN-15001 for the treatment of autoimmune disorders. CGEN-15001 is the extracellular region of a previously unknown membrane protein in the B7/CD28 family. The existence and potential utility of the newly discovered parent protein from which CGEN-15001 is derived was predicted in silico utilizing Compugen's LEADS Platform and other proprietary algorithms.
Autoimmune diseases develop when defects in the immune system lead the body to attack its own cells, tissues, and organs and include more than 80 chronic, and often disabling, illnesses. Among the most common autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and type-1 diabetes. Collectively, autoimmune diseases are among the most prevalent diseases, affecting an estimated 25 million people in the US.
CGEN-15001 is a novel soluble recombinant fusion protein corresponding to the extracellular region of the Compugen discovered parent protein. The discovery of the parent protein, which is a membrane protein, was accomplished through the incorporation in Compugen's LEADS Platform of additional algorithms specifically designed to predict novel members of the B7/CD28 family of co-stimulatory proteins. This approach relied on Compugen's proprietary understandings and modelling of genomic structure, gene expression, protein structural domains, and cellular localization. Compugen has filed for patent coverage on both the parent protein, which potentially has other medical uses such as a target for antibody therapeutics, and CGEN-15001.
The in vivo validation of CGEN-15001 utilized a mouse model of multiple sclerosis, relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE). In this model, administration of CGEN-15001 resulted in potent amelioration of the disease state. These results indicate that CGEN-15001 could have therapeutic utility for the treatment of multiple sclerosis and other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and type 1 diabetes. Earlier in vitro studies validated the predicted functional activity of CGEN-15001 as a new member of the B7/CD28 family proteins.
Professor Stephen Miller from Northwestern University, a leading scientist in this field who supervised the studies, stated, "Our studies have indicated robust disease suppressing activity for CGEN-15001 in the SJL R-EAE model, a recognized mouse model for multiple sclerosis. These studies have also demonstrated that CGEN-15001 has the unique ability to inhibit proliferation, differentiation, and cytokine production of pro-inflammatory Th1 and Th17 responses while at the same time sparing or actually promoting regulatory Th2-derived cytokines. As far as I am aware, this potentially very beneficial pattern of inhibiting Th1/Th17 while promoting Th2 responses is unique among the reagents targeting the B7 family of co-stimulatory molecules that have been published to date."
Compugen's VP R&D, Dr Zurit Levine stated, "We are extremely pleased by this further demonstration of the unique discovery capability that has been created at Compugen. In view of its recognized potential in the largely unmet and critical field of immune regulation, the B7/CD28 co-stimulation protein family has been an area of extensive research for a number of years. In our opinion, in addition to providing Compugen with a very attractive product candidate, the predictive discovery and experimental validation of a previously unknown member of this extensively researched protein family represents a major milestone in the transition from experimentally based therapeutic discovery to in silico prediction and selection."
The LEADS platform provides a comprehensive predictive view of the human transcriptome, proteome and peptidome, and serves as a rich infrastructure for the discovery of novel genes, transcripts and proteins.
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 modelling biological processes at the molecular level.