Author Interviews, Bristol Myers Squibb, Cancer Research, Pharmaceutical Companies / 19.03.2020 Interview with: Anat Cohen-Dayag, Ph.D. President and CEO Compugen What is the background for this announcement? Would you discuss Compugen’s underlying cancer hypothesis regarding the targeting of multiple checkpoint pathways to enhance tumor response? Response: Cancer immunotherapy has revolutionized the landscape for cancer treatments by providing new drug options leading to lasting benefits for patients. Yet, response rates vary greatly across different cancer indications, leaving a significant unmet medical need for many patients and a continuing challenge to discover new biological pathways that can serve for the development of new cancer immunotherapies for non-responsive and refractory patients. Using a computational approach which is designed to discover new biological pathways and drug targets, we identified PVRIG as a novel immune checkpoint and a newly discovered inhibitory pathway in the DNAM axis. Our hypothesis is that PVRIG and TIGIT (another inhibitory pathway discovered by us and others) are two parallel and complementary inhibitory pathways in the DNAM axis and that in certain tumor types and patient populations, there may be a need to block both PVRIG and TIGIT in order to enhance anti-tumor immune responses. Moreover, reported molecular intersections between the DNAM axis and the PD-1 pathway, the most prevalent pathway targeted by approved immunotherapies, suggest that there is a linkage between these three pathways. As such, our PVRIG inhibitor may work in synergy with PD-1 and TIGIT inhibitors, suggesting that various drug combinations may be required to address these three pathways based on their dominance in different cancer patients and cancer indications. With this recently announced Phase 1/2 triple combination study, we will be directly testing our hypothesis of an intersection between the three parallel immune checkpoint pathways – PVRIG, TIGIT and PD-1 – and that the simultaneous blockade of these pathways has the potential to synergistically enhance anti-tumor immune response and expand the reach of cancer immunotherapy to patients non-responsive or refractory to approved immunotherapies.  (more…)