A new target, a longer partnership
HOLON, Israel—Preclinical work has yielded some encouraging results for Compugen Ltd., who reported this week on data showcasing CGEN-15032's potential as a target for the development of first-in-class cancer therapies. The data came out of work performed under Compugen's research collaboration with the Johns Hopkins University School of Medicine, under the direction of Dr. Drew Pardoll, director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins and chairman of Compugen's Scientific Advisory Board.
Compugen discovered CGEN-15032 thanks to its immune checkpoint discovery platform. As noted on the company's website, “CGEN-15032 is a novel myeloid and epithelial immuno-oncology target. CGEN-15032 is expressed on cancer cells and subsets of myeloid cells within the tumor microenvironment. In-vitro checkpoint activity for CGEN-15032 was demonstrated in human and mouse experimental systems.” Tumor growth in knock-out mice that are CGEN-15032-deficient was found to be reduced compared to that of wild-type mice, and treating the knock-out mice with an anti-PD-L1 antibody led to additional reduction in tumor growth compared to wild-type mice treated with the same kind of antibody. Based on these results, Compugen noted in a press release that CGEN-15032 might be an immuno-suppressive component of the tumor microenvironment, and drugs that inhibit it—either alone or together with checkpoint inhibitors—could activate anti-cancer immune responses.
The collaboration between Compugen and JHU was originally announced on Dec. 18, 2014, with a focus on “further evaluation of selected novel B7/CD28-like immune checkpoint candidates discovered by Compugen for the potential treatment of cancer. This evaluation will include the candidates’ differentiation profile with respect to known checkpoints and their potential to serve either for monotherapy or in combination with other cancer treatments.” In conjunction with the news about CGEN-15032, Compugen also reported the extension of their collaboration with JHU to include new targets.
“The data we achieved with CGEN-15032, together with JHU, exemplifies the tremendous value of our collaboration, providing us with access to world-class immuno-oncology knowledge and expertise to successfully develop our immuno-oncology programs, and accelerate their path towards future human testing,” Dr. Anat Cohen-Dayag, president and CEO of Compugen said in a press release.
CGEN-15032 got some time in the spotlight at the recent 3rd annual CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, in Mainz/Frankfurt, Germany. Data was presented in an oral and a poster presentation, the latter of which was titled “Computational discovery and experimental validation of CGEN-15032 as a novel target for cancer immunotherapy.” Among other discoveries, Compugen reported that CGEN-15032 RNA is similarly expressed in normal and cancerous human tissues, noting also that expression of CGEN-15032 at the protein level was found to be higher in non-small cell lung cancer tissue compared to normal lung tissue. In addition, CGEN-15032 appears to inhibit tumor infiltrating lymphocyte activity similar to PDL1.
Compugen's discovery platform also enabled the identification of TIGIT and PVRIG, two novel immune checkpoints that Compugen is currently advancing through preclinical development. PVRIG, also known as CGEN-15029, is a novel B7/CD28-like immune checkpoint target candidate. According to Compugen, initial validation studies have demonstrated 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.”
Compugen notes on its website that “CGEN-15029/PVRIG is our highest priority mAb program and was selected to be advanced toward clinical testing.” Last June, the company chose COM701 as the lead therapeutic candidate for CGEN-15029/PVRIG.