Data published in Cancer Immunology Research indicate monotherapy and combination opportunities for COM701, a first-in-class cancer immunotherapy antibody targeting PVRIG
CompuGen (CGEN) announced the online publication of preclinical data demonstrating the role of PVRIG as a novel immune checkpoint and the potential of its first-in-class inhibitory antibody product COM701 targeting PVRIG, to serve as an effective cancer immunotherapy.
The findings were published in two peer-reviewed papers in Cancer Immunology Research, an American Association for Cancer Research publication. Both papers were co-authored by CompuGen’s scientists in collaboration with scientists from Johns Hopkins University School of Medicine. Headed by Drew Pardoll, M.D., Ph.D., Abeloff Professor of Oncology, Medicine, Pathology, and Molecular Biology and Genetics at Johns Hopkins University School of Medicine and Director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy and Co-Director of the Cancer Immunology Program at the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, and Chairman of CompuGen’s Scientific Advisory Board.
Explaining the significance of PVRIG, the immune checkpoint targeted by CompuGen drug COM710 in cancer immunotherapy, the President and CEO of CompuGen Anat Cohen-Dayag, Ph.D., said, “These are our first scientific publications discussing PVRIG, a new immune checkpoint we discovered computationally, and its inhibitory role within what we have termed the DNAM axis. The publication of these two peer-reviewed papers further validates our understanding of the PVRIG pathway and its importance in cancer immunotherapy. These preclinical data strongly support the rationale underlying our clinical development plan for COM701 and reinforces our expectation that targeting the PVRIG pathway will be foundational in expanding options for cancer patients non-responsive to other immunotherapies. The distinct position we hold in the immuno-oncology field as our Phase 1 study of COM701 in patients with advanced solid tumors continues to progress and the potential of COM701 as a treatment solution for cancer immunotherapy are strengthened by the recent clinical collaboration we announced with Bristol-Myers Squibb.” Dr. Cohen-Dayag added, “The paper entitled PVRIG and PVRL2 are induced in cancer and inhibit CD8+ T cell function demonstrates increased expression of PVRIG and its ligand, PVRL2, in multiple tumor types, including in tumors that are PD-L1 negative and therefore less likely to respond to PD-1 pathway inhibition.”
“PVRIG pathway expression appears to be dominant in ovarian, endometrial, and breast cancers. The study further demonstrates the parallel inhibitory roles of PVRIG and TIGIT in the DNAM signaling axis, and that dual targeting of the two results in synergistic activation of CD8+ effector T cells, suggesting an opportunity for effective clinical combinations of COM701 with anti-TIGIT antibodies.”
The findings have also demonstrated the potential of combining CompuGen product COM701 with Bristol-Myers (BMY) PD-1 inhibitors, which served as a key component in designing CompuGen’s ongoing Phase 1 study combination of COM701 with Opdivo®.
These results were further supported by mouse data showing that mice lacking PVRIG have increased anti-tumor T cell activity, and that tumor growth in these mice is reduced relative to wild-type mice. This tumor growth reduction is further enhanced in combination with TIGIT blockade, demonstrating in vivo the parallel inhibitory roles of PVRIG and TIGIT in the DNAM signaling axis.
Consistent with the finding in human systems, blocking both the PVRIG and the PD-1 pathways in mice also reduces tumor growth, providing an additional line of evidence for the therapeutic potential of the clinical combination of COM701 with Opdivo®.
CompuGen might have taken long in demonstrating the value of the sophisticated science it used in discovering and understanding the pathways of diseases at their molecular levels. In this peer-review publication, CompuGen scientists, together with Johns Hopkins University School of Medicine researchers and physicians ,explained the significance of CompuGen’s checkpoint protein inhibitor antibody COM701’s target, which makes the case for the firm’s product.