Bristol-Myers Squibb Accesses Small Molecules For Immunotherapy

Bristol-Myers Squibb, a pioneer in the development of monoclonal antibodies for use in cancer immunotherapy, added small-molecule capabilities last week with an acquisition and a research collaboration.

BMS will pay $800 million to acquire Flexus Biosciences, a privately held cancer drug discovery and development firm. The deal includes a drug candidate—an IDO1 inhibitor called F001287—and Flexus’s IDO/TDO discovery program. IDO and TDO are enzymes expressed by tumor cells to suppress the function of disease-fighting T cells, thus preventing the immune system from destroying certain types of tumors. Flexus shareholders could receive an additional $450 million in development milestones.

BMS also announced a research pact with Rigel Pharmaceuticals, a clinical-stage small-molecule specialist. The companies have agreed to pool research on the discovery, development, and commercialization of cancer immunotherapies based on Rigel’s portfolio of TGF-beta receptor kinase inhibitors. These molecules are designed to interfere with signaling from TGF kinases, which can undermine tumor-fighting immune responses.

The collaboration will focus on developing a new class of therapeutics aimed at increasing the immune system’s activity against various cancers, either as monotherapy or in combination with immune checkpoint inhibitors, including BMS’s Opdivo and Yervoy antibodies.

Under the terms of the agreement, BMS will obtain exclusive rights to develop and commercialize small-molecule drugs derived from Rigel’s library for cancer and other indications. BMS will pay $30 million up front, and Rigel will be eligible for milestone payments that could total more than $309 million for a successful compound approved in multiple indications.

Colin White, lead oncology analyst at Datamonitor Healthcare, says BMS will most likely pursue combination therapies, matching checkpoint-inhibiting antibodies that reactivate the immune system with small-molecule agents that inhibit cancer growth. “It would be difficult for these small molecules used as monotherapies to achieve the kind of efficacy results they are hoping for,” White says.

Other companies are pursuing similar combination immunotherapies. Last year, for example, Merck & Co. announced a collaboration with Incyte Corp. in which it will combine its anti-PD-1 checkpoint inhibitor with Incyte’s IDO1 inhibitor to treat advanced metastatic cancers.