CGEN-15001/ILDR2-Fc 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/ILDR2-Fc is an Fc fusion protein, consisting of the fusion of the extracellular region of CGEN-15001T to an IgG Fc domain. ILDR2 (internal designation CGEN-15001T) is a novel B7/CD28-like immune checkpoint target candidate discovered by Compugen using its broadly applicable predictive discovery infrastructure and licensed to Bayer in 2013.
CGEN-15001/ILDR2-Fc 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/ILDR2-Fc was shown to induce a durable long-term response suggestive of an immune tolerance mechanism. Additional studies demonstrated that CGEN-15001/ILDR2-Fc has a dual immuno-modulatory function manifested in attenuating inflammatory responses and promoting 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/ILDR2-Fc appears to be associated with its ability to enhance the differentiation of Tregs. CGEN-15001/ILDR2-Fc 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/ILDR2-Fc 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/ILDR2-Fc. This data demonstrated that immune tolerance can be transferred from diseased donor mice treated with CGEN-15001/ILDR2-Fc 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/ILDR2-Fc 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/ILDR2-Fc. 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.
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/ILDR2-Fc 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.
The discovery and validation of the ILDR2 protein as a novel checkpoint and its use as an Fc fusion protein for the treatment of autoimmune diseases were published in two peer-reviewed papers in The Journal of Immunology on February 5, 2018.