NEW YORK & CAMBRIDGE, Mass.—Often the news of breakthroughs or trials in cancer therapeutic discovery and development is about a specific type of cancer or closely related group of them, but recent news from Bristol-Myers Squibb Co. (BMS) and Vedanta Biosciences Inc. involves something more broad: advanced and metastatic cancers, and whether a combination of programmed death-1 (PD-1) immune checkpoint inhibitor Opdivo (nivolumab) from BMS and Vedanta’s immuno-oncology candidate VE800, described as “a rationally defined human bacterial consortium,” can make progress in treating such cancers.
According to the two companies, VE800 has been shown in research thus far to induce CD8+ T cells, potentiate the immune system’s attack of tumor cells and significantly amplify the effects of anti-PD-1 therapy in a range of preclinical models of cancer, including those sensitive and resistant to checkpoint inhibition. And these models, they say, support clinical research to explore whether modulating the microbiome with VE800 has the potential to broaden the efficacy of checkpoint inhibitors.
“Our lead, microbiome-based immuno-oncology candidate, VE800, is based on work conducted in collaboration with our co-founder, Dr. Kenya Honda, showing in preclinical models that certain gut-dwelling bacterial strains potentiate cytotoxic CD8+ T cells and enhance infiltration into tumors,” said Dr. Bernat Olle, co-founder and CEO of Vedanta Biosciences. “Through this collaboration our goal is to determine whether VE800 in combination with Opdivo can improve outcomes for patients with advanced or metastatic cancers.”
For BMS, the collaboration is an opportunity to explore the novel mechanisms of potential new assets that can work well with drugs in its own portfolio, said Dr. Fouad Namouni, head of development in the oncology division of Bristol-Myers Squibb, who added: “Vedanta Biosciences is a leading company focused on the characterization of immunomodulatory human gut commensals and the development of live bacterial products for the potential treatment of human diseases. Our collaboration with Vedanta Biosciences will allow us to gain a deeper understanding about the emerging microbiome landscape, its role in oncology and the potential to improve outcomes for patients with advanced or metastatic cancer.”
And BMS is willing to do more than just share data and work together with its partner. In conjunction with this collaboration—and subject to the completion of due diligence, the negotiation by the parties of definitive transaction agreements and the receipt by BMS of all requisite approvals—Bristol-Myers Squibb has indicated that it intends to make an equity investment in Vedanta Biosciences. Should the investment go through, Vedanta would still maintain control of its VE800 program, including global R&D and commercial rights.
“Checkpoint inhibitors, particularly PD-1 antibodies, have been a major advance in cancer therapy; however, a large proportion of patients either do not respond or have response of brief duration to those new therapies,” remarked Dr. Jeffrey Weber, deputy director of the Laura and Isaac Perlmutter Cancer Center and Professor of Medicine at NYU Langone Health in the news release issued by BMS and Vedanta. “Alteration of the gut microbiome could play a significant role in enhancing the effectiveness of checkpoint inhibitors and, with increased understanding, may also be used to select for patients who would benefit most from these immunotherapies.”
This news of the BMS-Vedanta collaboration comes just a couple weeks after less-stellar news from Bristol-Myers Squibb that the Phase 3 CheckMate-451 study did not meet its primary endpoint of overall survival with Opdivo 1 mg/kg in combination with Yervoy (ipilimumab) 3 mg/kg vs. placebo as a maintenance therapy for patients with extensive-stage small cell lung cancer without disease progression after completion of first-line platinum-based chemotherapy.
On the other hand, just before that news, BMS announced that the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion recommending approval of the Opdivo plus low-dose Yervoy combination to include first-line treatment for patients with intermediate- and poor-risk advanced renal cell carcinoma.