CGEN-15029 is the internal designation for PVRIG, a novel B7/CD28-like immune checkpoint target candidate discovered by Compugen.
Initial validation studies show that expression of CGEN-15029/PVRIG in T cells inhibits their activation by melanoma cells, consistent with an immune suppressive role of the target in the tumor microenvironment. The target possesses signature immune-checkpoint receptor characteristics, including expression in relevant subsets of T- and NK-cells, with particularly high expression in lymphocytes that populate the tumor microenvironment (known as tumor infiltrating lymphocytes or TILs). A binding partner for CGEN-15029/PVRIG has also been identified, which enables a clear path towards selection of inhibitory antibodies and their therapeutic development. CGEN-15029/PVRIG is our highest priority mAb program and was selected to be advanced toward clinical testing.
In June 2016, COM701 was selected as the lead therapeutic candidate for CGEN-15029/PVRIG. COM701 is undergoing preclinical development activities in preparation for advancement to clinical trials. The selected humanized lead antibody demonstrated potent, reproducible enhancement of T cell activation, consistent with the desired mechanism of action of activating T cells in the tumor microenvironment to generate anti-tumor immune responses.
CGEN-15029/PVRIG immune checkpoint represents a new inhibitory component of the known TIGIT axis. Consistent with the placement of PVRIG in the TIGIT axis, antibody blockade of both TIGIT and PVRIG had an additive effect on human T cell stimulation, indicating the potential of the two to generate enhanced immune response against the cancer. Moreover, antibodies targeting the mouse PVRIG developed by the Company were assessed in vivo for effects on tumor growth inhibition in mouse models, commonly used to study immune checkpoint inhibitors. In these studies, antibodies that block the mouse PVRIG/PVRL2 interaction, similar to those generated against the human target, were shown to inhibit tumor growth when used in combination with PD1 pathway blockade. These results were further reinforced when tumor growth was tested in knock-out (KO) mice. Tumor growth was significantly reduced in KO mice, where the PVRIG gene was removed. Consistent with the antibody combination data, this effect was even further enhanced in the KO mice when they were treated with anti-PDL1 blocking antibodies.
The Company plans to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration towards the end of the first quarter of 2018.