Targeting TIGIT

At the recent Annual Meeting of the Society for Immunotherapy of Cancer, the company disclosed data demonstrating that the CGEN-15029/PVRIG immune checkpoint discovered by Compugen represents a new inhibitory component of the known TIGIT axis. Data was also presented that strongly support combining the company’s COM701 anti-PVRIG antibody, which is now in preclinical studies, with an anti-TIGIT antibody.

Compugen hypothesized that dual blockade of the two negative costimulatory arms of the axis— TIGIT and PVRIG—should result in a more robust T cell response, and therefore possibly a better anti-tumor immune response. To support this, in-vitro studies were conducted which show that dual blockade of both TIGIT and PVRIG increases the activity of tumor-infiltrating T cells beyond the level achieved by blocking each alone.

Leveraging its knowledge, Compugen initiated a therapeutic antibody program targeting TIGIT to complement its CGEN-15029 program.

Dr. Anat Cohen-Dayag, president and CEO of Compugen, stated, “We are excited to disclose our therapeutic program for TIGIT, an immuno-oncology target of high industry interest. Our efforts to date have demonstrated the potential enhanced efficacy of a combination treatment of a TIGIT antibody together with COM701. TIGIT and PVRIG represent two distinct arms of the same biological pathway. Based on this and our experimental data demonstrating synergistic activation of T cells, we believe there is a significant added value to developing both arms of this potential combination therapy. Currently, we are in the process of developing a therapeutic antibody for CGEN-15137/TIGIT, and expect to select the lead antibody for this target by end of the first quarter of 2017.”

“It is becoming clearer that more closely tailored combination therapies will be able to address, in the future, a higher percentage of cancer patients.” he continued. “We therefore have high expectations for our diversified portfolio of novel immune checkpoint candidates.”

Internally designated as CGEN-15137, TIGIT was discovered by Compugen utilizing its in-silico predictive discovery infrastructure and experimentally validated as an immune checkpoint. The findings were published by Compugen in the October 2009 issue of the Proceedings of National Academy of Sciences. In the same year, two other groups also published papers disclosing the same checkpoint. Antibodies targeting TIGIT being developed by others have entered Phase 1 clinical testing in recent months.