HOLON, Israel—Compugen Ltd., a therapeutic discovery company, in June disclosed new data for COM701, an immuno-oncology therapeutic antibody candidate, which demonstrated potential for dual- and triple-combination therapy with antibodies targeting TIGIT and PD-1. In addition to monotherapy applications, this combination approach may expand the responsive cancer patient population, including those who are partially responsive or refractory to PD-1 inhibitors. Recent expression data in human tumors point to the potential of COM701 to treat cancer patients for whom current PD-1 pathway inhibitors have shown limited efficacy.
The preclinical data was highlighted in a poster presentation at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, entitled “Discovery and Development of COM701, a Therapeutic Antibody Targeting the Novel Immune Checkpoint PVRIG.” The poster presented new in-vivo data demonstrating that PVRIG-blocking antibodies reduced the growth of tumors in TIGIT-deficient mice, providing further support of the rationale for the clinical combination of COM701 with TIGIT blockade.
COM701 targets PVRIG, a novel B7/CD28-like immune checkpoint target candidate. COM701 is a humanized hybridoma antibody that binds to PVRIG with high affinity and blocks its interaction with PVRL2. Blockade of PVRL2 binding by COM701 results in potent, reproducible enhancement of T cell activation, consistent with the desired mechanism of action of activating T cells in the tumor microenvironment to generate antitumor immune responses. COM701 combined with antagonist anti-TIGIT antibodies has an additive effect on human T cell stimulation, indicating the potential of the combination to generate enhanced immune response against cancer.
New in-vitro data demonstrate that COM701 can synergistically increase T cell activation in combination with either anti-TIGIT or anti-PD-1 antibodies. The combination of COM701 with an anti-TIGIT antibody resulted in equal or greater T cell stimulation than either of those antibodies in combination with anti-PD-1. T cell activation was further enhanced by the triple combination of PVRIG/TIGIT/PD-1 blockade when targeting tumor cells with high PD-L1 expression. This suggests a possible treatment path for cancer patients whose tumors express PD-L1, including those who are refractory to anti-PD-1 therapeutics.
Additionally, analysis of multiple human solid tumors—including those of lung, kidney, endometrial and head and neck cancers—identified expression of PVRIG and its ligand PVRL2, suggesting that patients with such cancers could benefit from treatment with COM701. In certain tumors that were negative for PD-L1 expression, analysis revealed high expression of PVRL2. This suggests the potential for COM701 to treat cancers where current PD-1 pathway inhibitors have shown limited efficacy.
Compugen also reported a recent clinical advisory meeting in Chicago, in anticipation of initiating COM701 clinical studies next year. Key clinical physicians in immuno-oncology participated in the meeting, which was led by members of Compugen’s scientific advisory board.
“The promising data presented at ASCO further demonstrate the clinical and commercial potential of COM701 for both mono- and combination therapy, including in combination with our anti-TIGIT drug candidate COM902,” said Dr. Anat Cohen-Dayag, president and CEO of Compugen. “It is our belief that these therapies have the potential to expand the responsive cancer patient population. Also, we were pleased to host our first clinical advisory meeting for COM701 with key oncologists in the immuno-oncology space. The data and discussion further supported the initiation of clinical trials for this potential first-in-class therapy.”