Bristol Myers Squibb catches the SHP2 wave in a new collaboration deal with BridgeBio
Once considered “undruggable,” the phosphatase enzyme SHP2 has seen recent interest from a suite of Big Pharmas, including AstraZeneca, Amgen, Novartis and Merck. Now Bristol Myers Squibb is getting in on the action, with a deal to pair its PD-1 superstar Opdivo with BridgeBio’s SHP2 inhibitor for difficult-to-treat cancers.
BMS and BridgeBio took the wraps off the non-exclusive, co-funded collaboration early Tuesday morning. The “catalyst,” BridgeBio CBO Michael Henderson said, was last year’s virtual JP Morgan conference, where the companies met to discuss early preclinical results they were seeing between SHP2 and immuno-oncology therapies.
SHP2 is a phosphatase that links growth factor, cytokine and integrin signaling with the downstream RAS/ERK MAPK pathway to regulate cellular proliferation and survival. What does that mean? Overexpression of SHP2, for instance, has a downstream signaling effect on tumor cell growth. It’s been suggested that SHP2 has an effect on the tumor microenvironment, and sensitivity to immuno-oncology therapy.
The partners will put Opdivo and BBP-398 — the SHP2 inhibitor BridgeBio licensed from MD Anderson back in 2017 — in a Phase I/II study as a doublet therapy, as well as a triplet therapy along with a KRAS G12C inhibitor in non-small cell lung cancer patients with KRAS mutations.
Henderson declined to say much about the financial terms of the deal, except that BridgeBio will sponsor the study and BMS will provide Opdivo. The partners will share costs for the combo trial.
“Cancers that are driven by hyperactive MAPK signaling, including certain RAS mutations such as KRASG12C, may be sensitive to SHP2 inhibition,” Frank McCormick, chairman of oncology at BridgeBio, said in a statement. “With this collaboration, we hope to better elucidate our SHP2 inhibitor’s ability to enhance immuno-oncology and other targeted therapies to potentially provide options for patients with difficult-to-treat cancers as quickly and safely as possible.”
BridgeBio is also testing the candidate as a monotherapy, and the scientists expect to nail down the recommended Phase II dose in the next six to 12 months.
Revolution Medicines struck a deal back in October to pair its lead SHP2 inhibitor, RMC-4630, with AstraZeneca’s KRAS G12C program. That same candidate attracted Sanofi for a partnership back in 2018 that involved $50 million upfront, 80% of the R&D cost, and a swath of milestones adding up to $520 million. Taiho and Astex granted Merck an exclusive license to their joint SHP2 program in January. And in April, Anavo Therapeutics launched with $24 million in seed funding to bust the doors on phosphatases wide open.
“I think early on in the class, it’s too early to tell where the class is going to end up, especially with such limited data that’s been released,” Henderson said. “We’re very excited to collaborate with BMS on this.”