11 October 2018 - - US-based biopharmaceutical company Bristol-Myers Squibb Company (NYSE: BMY) and Israel-based therapeutic discovery and development company Compugen (NASDAQ: CGEN) have entered into a clinical trial collaboration to evaluate the safety and tolerability of Compugen's COM701, an investigational anti-PVRIG antibody, in combination with Bristol-Myers Squibb's programmed death-1 immune checkpoint inhibitor Opdivo (nivolumab), in patients with advanced solid tumors, the companies said.

In conjunction with this collaboration, Bristol-Myers Squibb will make a USD 12m equity investment in Compugen.

Compugen will sponsor the ongoing two-part Phase 1 trial, which includes the evaluation of the combination of COM701 and Opdivo in four tumor types, including non-small cell lung, ovarian, breast and endometrial cancer.

This collaboration is also designed to address potential future combinations, including trials sponsored by Bristol-Myers Squibb to investigate combined inhibition of checkpoint mechanisms, such as PVRIG and TIGIT.

The clinical combination of multiple immune checkpoint inhibition is designed to test the biological rationale of the PVRIG pathway and the synergistic activity demonstrated in preclinical models.

Under the terms of the share purchase agreement, Bristol-Myers Squibb will make a USD 12m investment in Compugen comprised of 2,424,243 shares of Compugen stock purchased at USD 4.95 per share, representing a 33% premium over the average closing price on the last 20 NASDAQ trading days.

The investment is expected to close on or about October 12, 2018, subject to closing conditions.
Specific terms of the agreement can be found here.

COM701 is a humanised antibody that binds with high affinity to PVRIG, a novel B7/CD28-like immune checkpoint target candidate discovered by Compugen, blocking the interaction with its ligand, PVRL2.

Blockade of PVRIG by COM701 has demonstrated potent, reproducible enhancement of T cell activation, consistent with the desired mechanism of action of activating T cells in the tumor microenvironment to generate anti-tumor immune responses.

In addition, COM701 combined with antagonist anti-PD-1 antibodies has demonstrated synergistic effects on human T cell stimulation, indicating an intersection of the PVRIG and PD-1 inhibitory pathways and the potential of these combinations to further enhance immune response against tumors.

PVRIG and TIGIT constitute parallel immune checkpoint pathways that counteract DNAM-1, a costimulatory molecule on T cells and NK cells. Preclinical data for COM701 suggest that PVRIG may be a dominant checkpoint in diverse patient populations with tumors that express elevated PVRL2 as compared to expression of the TIGIT ligand PVR.

This include patients with breast, endometrial, and ovarian cancers. In addition, expression studies show that PVRIG, TIGIT, and their respective ligands, are expressed in a broad variety of tumor types, such as those noted above, as well as lung, kidney, and head and neck cancers.

In these tumors the blockade of both TIGIT and PVRIG may be required to sufficiently stimulate an anti-tumor immune response, with or without additional PD-1 pathway blockade.

Opdivo is a programmed death-1 immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response.

By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo's global development programme is based on Bristol-Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a range of tumor types.

To date, the Opdivo clinical development programme has enrolled more than 25,000 patients.

The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union, and Japan.

In October 2015, the company's Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.