CGEN-15001 is our lead program for autoimmune diseases. It is a first-in-class therapeutic candidate of a novel inhibitory checkpoint pathway, with the potential to restore immune tolerance and re-establish immune homeostasis, thus potentially offering patients a durable therapeutic response and a safer treatment profile.
CGEN-15001 is an Fc fusion protein, consisting of the fusion of the extracellular region of CGEN-15001T to an IgG Fc domain. CGEN-15001T is a novel immune checkpoint discovered by Compugen using its broadly applicable predictive discovery infrastructure.
CGEN-15001 has a broad preclinical data package supporting its unique mode-of-action and therapeutic potential. It was previously shown to be effective in treating several autoimmune diseases in animal models, including models of multiple sclerosis, rheumatoid arthritis, type 1 diabetes and psoriasis. In some of these models, a short period of treatment with CGEN-15001 was shown to induce a durable long-term response suggestive of an immune tolerance mechanism. Additional studies demonstrated that CGEN-15001 has a dual immuno-modulatory function manifested in attenuating inflammatory responses and promoting regulatory and anti-inflammatory activities, including the differentiation of regulatory T cells (Tregs), a population of immune cells that plays a pivotal role in induction and maintenance of immune tolerance. Importantly, the long term therapeutic effect of CGEN-15001 appears to be associated with its ability to enhance the differentiation of Tregs. CGEN-15001 demonstrated anti-inflammatory effects in translational studies both in healthy donors’ cells as well as in cells from RA patients, thereby confirming that the CGEN-15001 pathway is functional and responsive in these autoimmune patients.
In January 2017, we announced new animal model results demonstrating restoration of immune tolerance by CGEN-15001. This data demonstrated that immune tolerance can be transferred from diseased donor mice treated with CGEN-15001 to recipient naïve mice. More importantly, this immune tolerance was shown to be antigen-specific, as the transfer of T cells from diseased donor mice treated with CGEN-15001 resulted in protection of the recipient mice from developing the disease in response to the specific antigen driving the disease at the time of treatment with CGEN-15001. In comparison to current therapeutic approaches that generally suppress the immune system, tolerance induction has the potential to provide a sustained resolution of the disease without compromising the immune system’s capacity to fight infections and malignancies.
We have further shown that the durable therapeutic response to CGEN-15001 treatment is potentially maintained via Tregs. The promise of this class of therapeutic candidates based on immune checkpoints is to potentially affect immunological processes underlying autoimmunity, thereby potentially providing long-term therapeutic solutions for patients. CGEN-15001 represents a paradigm shift from standard-of-care drugs and has the potential to be effective in patients with inadequate response to current treatments across autoimmune therapeutic indications.