John Hunter, Ph.D., site head and vice president of Antibody R&D at Compugen USA, a subsidiary of Compugen Ltd., publicly announced the results of CGEN-15029, the lead research program in their immuno-oncology product portfolio. CGEN-15029 is one of multiple novel immune checkpoint target candidates, discovered by a computational modeling approach developed in-house.
Immune checkpoints refer to several inhibitory pathways hardwired into the immune system that are important for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in tissues, minimizing collateral tissue damage. A therapeutic blockade of immune checkpoints triggers anti-tumor immunity, helping the patient’s immune system recognize and attack the tumor cells. This concept provides promising clinical benefits, like long-term survival even for end-stage patients.
Hunter talked about the details of the successful discovery of blocking antibodies, and shared biophysical data about the lead antibodies. He reviewed the expression data for CGEN-15029 in subsets of T-cells and NK-cells, discovering expression in tumor infiltrating lymphocytes (TILs) that populate the tumor microenvironment of several types of cancers.
Particularly, gene expression of CGEN-15029 was demonstrated to be significantly correlated with immune checkpoints such as PD-1, TIM-3, and TIGIT in several solid tumors, supporting the idea that it has a similar role in preventing T-cell response to cancer cells. This emphasized their previous findings, which demonstrated that higher expression of CGEN-15029 inhibits T-cell activation.
Hunter also presented a panel of recently discovered antibodies that can bind to CGEN-15029, disrupting its interaction with ligands and stimulating an immune response in the tumor microenvironment, allowing the immune system to attack tumor cells.
“We are pleased to present today these important results for therapeutic antibodies in our lead internal program CGEN-15029, a novel immune checkpoint target candidate for the treatment of cancer,” Compugen President and CEO Anat Cohen-Dayag, Ph.D., said in a press release. “Our identification of a binding partner during CGEN-15029’s target validation efforts has provided a much clearer path towards discovery and development of therapeutic antibodies against the target.
“Accordingly, we have successfully progressed through antibody discovery and identified antibodies that meet our key selection criteria for therapeutic candidates. We are now at the stage of selecting the therapeutic clinical candidate which we plan to advance to IND enabling studies, and are finalizing work plans for such advancement on various fronts, including manufacturing, preclinical, and regulatory,” Cohen-Dayag said. “We consider CGEN-15029 to be a very promising therapeutic and commercial opportunity, and look forward to disclosing further information regarding the program in the coming months.”
“The accumulating clinical results for the small number of cancer immunotherapy drugs currently available show that while some patients achieve remarkable long-term remissions, the majority of cancer patients experience little, if any, benefit,” Cohen-Dayag said. “This highlights the need for additional checkpoint-based therapies and other immuno-oncology drugs in order to provide a more inclusive solution to cancer.
“Therefore, the continuing demonstration of the potential value for the novel immune checkpoint target candidates discovered by the company, such as CGEN-15029, in a variety of cancers and immune cell sub-types is very exciting from both a medical and commercial standpoint,” Cohen-Dayag said.