Compugen Publishes Paper on PVRIG's Unique Biology and Therapeutic Potential

Compugen Ltd., a clinical-stage company specializing in cancer immunotherapy and computational target discovery, has announced the online publication of a peer-reviewed paper in the journal Cancer Immunology Research. The paper, titled "PVRIG is expressed on stem-like T cells in dendritic cell-rich niches in tumors and its blockade may induce immune infiltration in non-inflamed tumors," explores the role of PVRIG in cancer and presents new insights into how its inhibition could enhance anti-tumor immune responses.

Anat Cohen-Dayag, Ph.D., President, and CEO of Compugen, emphasized the significance of adding another component to optimize the anti-tumor response when combining anti-TIGIT and anti-PD-(L)1 therapies. She highlighted that Compugen was the first to identify the novel immune checkpoint PVRIG through its computational discovery platform. Preclinical data suggested potential synergy in blocking PVRIG, TIGIT, and PD-1 pathways. Phase 1 studies demonstrated that the triple blockade involving PVRIG, using Compugen's antibody COM701 in combination with anti-TIGIT and anti-PD-1 therapies, led to durable clinical responses and favorable safety profiles in cases that typically do not respond to immunotherapy. These responses were linked to the infiltration and proliferation of T cells in the tumor microenvironment, a rare occurrence in less inflamed tumors.

Eran Ophir, Ph.D., Chief Scientific Officer at Compugen, added that the published paper provides an advanced understanding of PVRIG's unique biology and its role in cancer. Using single-cell RNA sequencing and spatial transcriptomic analysis, the study demonstrated differentiated expression of PVRIG and its ligand PVRL2 on early differentiated stem-like memory T cells and dendritic cells, respectively. This interaction plays a crucial role in inhibiting the recruitment and proliferation of T cells within the tumor microenvironment. The unique biology of PVRIG suggests a novel approach for potentially overcoming resistance to immunotherapy by sensitizing tumors to other immune checkpoint inhibitors.

Compugen is recognized for its predictive computational discovery capabilities, which it leverages to identify new drug targets and biological pathways for cancer immunotherapies. The company has developed two proprietary product candidates: COM701, a potential first-in-class anti-PVRIG antibody, and COM902, a potential best-in-class antibody targeting TIGIT for treating solid tumors. Compugen also has a clinical stage partnered program, rilvegostomig (previously AZD2936), a PD-1/TIGIT bispecific antibody being developed by AstraZeneca under a license agreement. Additionally, Compugen's pipeline includes various early-stage immuno-oncology programs, the most advanced being COM503, a potential first-in-class high-affinity antibody that is in IND enabling studies and licensed to Gilead. This antibody aims to block the interaction between IL-18 binding protein and IL-18, freeing natural IL-18 in the tumor microenvironment to inhibit cancer growth.

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