HOLON, Israel—In early November, Compugen Ltd., a clinical-stage cancer immunotherapy company and a major player in predictive target discovery, disclosed preclinical results from its COM902 anti-TIGIT program supporting its potential clinical use in various combinations with PD-1 inhibitors and COM701, a first-in-class PVRIG inhibitor.
The findings were presented in a poster titled “COM902, a Novel Therapeutic Antibody Targeting TIGIT Augments T Cell Function and the Activity of PVRIG Pathway Blockade In Vitro and In Vivo” at the 34th Annual Meeting of the Society for Immunotherapy of Cancer in National Harbor, Md., on Nov. 9.
“These new preclinical data further substantiate our theory that TIGIT and PVRIG are part of a foundational immuno-oncology axis, the DNAM axis,” said Dr. Anat Cohen-Dayag, president and CEO of Compugen. “We believe that a combined treatment of COM902 with COM701, our first-in-class PVRIG antibody, has the potential to enhance the clinical impact of cancer immunotherapy in patients unresponsive to approved treatments. We look forward to advancing COM902 to the clinic early next year.”
Key findings in the poster include:
- Broad expression of TIGIT and PVRIG ligands, PVR and PVRL2 in solid tumors
- Superior binding affinity of COM902 to T cells with similar and or greater in-vitro function compared to several clinical anti-TIGIT antibodies
- Increased T cell activation by COM902 on tumor infiltrating lymphocytes, which was further enhanced by combination with COM701
- Reduced mouse melanoma tumor growth in TIGIT and PVRIG knockout mice, with further tumor growth reduction in TIGIT/PVRIG double knockouts
- COM902 inhibited tumor growth and increased survival when combined with anti-PVRIG or anti-PD-L1 antibodies in a mouse model of colon cancer.
COM902, a high-affinity, fully human antibody targeting TIGIT, was developed for combination treatment with COM701. Preclinical data demonstrate that TIGIT inhibition, either alone or in combination with other checkpoint inhibitors, can enhance T cell activation and increase antitumor immune responses. Parallel inhibition of TIGIT and PVRIG, the two coinhibitory arms of the DNAM-1 axis, results in synergistic effects on effector T cell function and tumor growth inhibition in various model systems, which can be further increased with the addition of PD-1 blockade.
Based on preclinical data these combinations may be clinically important for enhancing antitumor immune response and expanding the patient population responsive to checkpoint inhibition. Compugen discovered TIGIT in 2009 by leveraging its immune checkpoint computational discovery platform, through which PVRIG was also discovered.