2 min readPotential Blocking Antibodies Discovered Against Novel Target Candidate in Cancer Immunotherapy
Holon, Israel — Details of recent progress achieved in the CGEN-15029 antibody program by Compugen Ltd., including the successful discovery of blocking antibodies and biophysical information for the lead antibodies, were announced today at the New York Academy of Sciences’ Emerging Approaches to Cancer Immunotherapy conference.
Dr. John Hunter, Site Head and Vice President of Antibody R&D at Compugen USA, Inc., a wholly owned subsidiary of Compugen Ltd., presented results for the lead internal program in the Company’s immuno-oncology therapeutics pipeline. CGEN-15029 is one of the multiple novel immune checkpoint target candidates discovered by the Company through the use of its predictive in silico technology.
Immune checkpoints are inhibitory receptors and their ligands, which are crucial for the maintenance of self-tolerance (that is, the prevention of autoimmunity) and for the protection of tissues from damage when the immune system is responding to pathogenic infection or other injuries.
These immune checkpoints, which are “hijacked” by tumours to block the ability of the immune system to destroy the tumour (immune resistance), have emerged as promising targets for cancer immunotherapy, and have shifted the treatment paradigms for several major cancer types.
Therapeutic blockade of immune checkpoints boosts anti-tumour immunity, enabling the patient’s immune system to recognize and attack the tumour cells, and mount durable anti-tumour responses and tumour destruction.
In his presentation, Dr. Hunter reviewed the expression data for CGEN-15029 in relevant subsets of T and NK cells, demonstrating expression in tumour infiltrating lymphocytes that populate the tumour microenvironment of multiple types of cancers.
Specifically, expression of CGEN-15029 was shown to be highly correlated with the known immune checkpoints PD-1, TIM-3 and TIGIT in various solid tumours, suggesting that it plays a similar role in preventing T-cell response to tumour cells, and consistent with previous experiments in which the Company has demonstrated that increased expression of CGEN-15029 inhibits T-cell activation.
Additional data was presented demonstrating the binding of CGEN-15029 to its ligand (“binding partner”), which was identified during CGEN-15029’s target validation efforts.
Dr. Hunter also disclosed that Compugen has identified a panel of antibodies that bind to CGEN-15029 with very high affinity and disrupt the interaction with its ligand, a mechanism of action common to other antibodies serving as immune checkpoint inhibitors.
Based on the expression data and additional mechanistic results presented for selected antibodies, such antibody therapeutic candidates targeting CGEN-15029 are predicted to exert an immune stimulatory effect in the tumour microenvironment, thus allowing the immune system to attack the cancer 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,” stated Dr. Anat Cohen-Dayag, Compugen’s President and Chief Executive Officer. “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.”
Dr. Gohen-Dayag disclosed that Compugen team is now at the stage of selecting the therapeutic clinical candidate which they plan to advance to IND enabling studies, and are finalizing work plans for such advancement on various fronts, including manufacturing, preclinical and regulatory.
“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. This highlights the need for additional checkpoint-based therapies and other immuno-oncology drugs in order to provide a more inclusive solution to cancer. 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,” added Dr. Gohen-Dayag.
Article adapted from a Compugen news release.
Conference: Emerging Approaches to Cancer Immunotherapy. 29 February, 2016:Click here to view.