BI-770371

Boehringer Ingelheim is giving up on a Phase 2 MASH program using an experimental cancer drug that goes after the CD47 pathway, one of oncology’s most alluring and troublesome therapeutic approaches. The candidate, an anti-SIRPα monoclonal antibody called BI 770371, is designed to block the CD47 “don’t eat me” signal that cancer cells use to shield themselves from the immune system. For years, drugmakers have tried ways of drugging CD47, but have been thwarted by disappointing readouts and safety concerns. In patients with MASH, Boehringer and its partner OSE Immunotherapeutics had hoped the drug could help improve fibrosis of the liver. But a Phase 2 trial “did not show efficacy supporting further development in this indication,” a Boehringer spokesperson told Endpoints News. Unlike other drugs that target CD47 directly, BI 770371 is designed to target a receptor called SIRPα on the cell surface, blocking its interaction with CD47. Boehringer and OSE said the MASH failure won’t impact BI 770371’s development in cancer, which was the original basis for a 2018 collaboration deal that gave OSE €15 million upfront. The companies later expanded the partnership to cardiovascular-renal-metabolic diseases. Boehringer said multiple Phase 1 programs are ongoing in cancer. It didn’t share any further details about those programs or the MASH failure, except to say that the drug was well-tolerated and the safety profile was “manageable.” It’s also not the only drugmaker to hit a roadblock with the CD47 approach outside of cancer. Bitterroot Bio, which was founded by some of the researchers who helped pioneer CD47, appears to have returned to discovery work after an attempt to take forward a CD47 drug for atherosclerosis. The company had begun dosing patients in a Phase 2a study for atherosclerosis. But last month, former Bitterroot CEO Pavan Cheruvu revealed that the company was refocusing on “discovery biology and translational research.” Cheruvu said in a January LinkedIn post announcing his departure that “even with flawless execution, biology doesn’t always go according to plan.” He said the company is still in pursuit of CD47, however, and the company has said it remains confident “in the potential of the CD47 pathway to treat atherosclerosis.” Bitterroot didn’t immediately respond to requests for comment on Monday and Tuesday. Editor’s note: This story has been updated to clarify 770371’s mechanism of action.

After AbbVie handed early-stage development rights for a mAb back to OSE Immunotherapeutics, the immunology-focused drug developer is pausing the programme's development. AbbVie paid $48 million upfront in 2024 for an exclusive global license to OSE-230 and is on the hook for up to $665 million in milestones. The mAb, designed to activate the GPCR target ChemR23 and modulate both macrophages and neutrophils, was in development for chronic and inflammatory diseases. However, OSE disclosed in December that, under an amendment to the licensing deal, it will be responsible for preclinical and Phase I development of OSE-230, noting that such development is "contingent upon securing adequate funding." If OSE successfully completes Phase I testing, AbbVie, which still holds an exclusive license to the asset, would resume full development and commercialisation rights.Now it's looking like OSE doesn't have the capital to commit towards OSE-230's early development right now. The company said Monday it will pause development of the programme and instead focus on a pair of late-stage assets: Tedopi, a T-cell epitope-based cancer vaccine in Phase III testing for non–small-cell lung cancer (NSCLC) and lusvertikimab (OSE-127), a mAb directed against CD127 being explored for chronic pouchitis and hidradenitis suppurativa. Another asset affected by the reprioritisation is OSE's CLEC‑1 programme in oncology, for which the company will discontinue all exploratory research activities. While OSE called the programme "scientifically promising," it noted that the early myeloid checkpoint target "does not fall within…immediate clinical or partnership priorities.""By stepping away from selected early‑stage programmes which were not expected to generate meaningful value inflection points over our three-year strategic programme, we are concentrating our resources where OSE can create the greatest value in the near term," said CEO Marc Le Bozec. "This strengthened focus enhances our ability to deliver late‑stage clinical progress, secure meaningful partnerships, and accelerate Tedopi and lusvertikimab."Boehringer mAb's MASH dudAlong with the pipeline reshuffle, OSE also shared that another partnered programme has hit a bump in the road.The biotech first linked up with Boehringer Ingelheim in 2018 to jointly develop an anti-SIRPα antibody for cancer; in 2024, the German pharma elected to expand the development programme for BI 770371 to include cardiovascular-renal-metabolic (CRM) diseases, paying a one-time "partial royalty buy-out" of €25.3 million ($27.4 million).However, the play doesn't seem to have paid off. OSE said that Boehringer has discontinued development of BI 770371 in metabolic dysfunction-associated steatohepatitis (MASH) after it "did not demonstrate efficacy" in an exploratory Phase II study. OSE emphasised that the candidate's development in oncology is unaffected, with multiple Phase I studies underway.