Eli Lilly and Rigel Pharmaceuticals partnered in February 2021 to advance a pair of RIPK1 blockers, but the pharma in October last year pulled the plug on one of these programs for central nervous system indications.
Eli Lilly is walking away from RIPK1 partner Rigel Pharmaceuticals, turning its back on a pair of investigational assets—and dealing the already-beleaguered modality another blow.
The termination will take effect on June 15, according to an SEC filing from Rigel that is dated April 16 but was posted on Tuesday. After that date, Lilly will hand back rights to two investigational RIPK1 inhibitors and will no longer be on the hook for milestones or other payments to Rigel.
The Delaware biotech has not specified plans for the RIPK assets moving forward. In the SEC document, Rigel said only that the company “expects to regain full rights to the licensed compounds and related programs” after the partnership formally ends. Rigel will also assess the financial impacts of Lilly’s withdrawal.
Lilly and Rigel linked up in February 2021, with the pharma putting forward $125 million to license two RIPK1 blockers, a drug class that works by regulating inflammation and cell death. Rigel was eligible for up to $835 million in milestones plus tiered royalties on any products that reached the market.
The partners’ progress throughout the years has been largely quiet, but in October 2025, Lilly called off their central nervous system program, Rigel announced in its third-quarter 2025 earnings report. The biotech did not reveal Lilly’s reasoning for ending the program, but the pharma’s decision brought the partners down to just one remaining asset: ocadusertib.
Designed to be orally available, ocadusertib is in a mid-stage trial for rheumatoid arthritis. It is unclear how the partnership termination will affect this study, but the trial is listed as “recruiting” on the federal clinical trials database and completion is set for July this year.
Lilly’s decision to step away from Rigel continues the years-long losing streak in the RIPK space, with many of the industry’s biggest players moving away from the modality.
In October 2024, for instance, Sanofi and development partner Denali Therapeutics cut a Phase 2 multiple sclerosis study after the RIPK1 inhibitor oditrasertib failed to significantly improve serum levels of neurofilament light chain, a key disease biomarker. In April that year, Sanofi scrapped another mid-stage study of oditrasertib in amyotrophic lateral sclerosis, likewise due to disappointing results.
Roche also added to the RIPK1 scrap heap last month, terminating a mid-stage study for flizasertib in acute kidney injury patients undergoing cardiac surgery. Early findings “indicated that the study was unlikely to demonstrate a significant clinical benefit,” a spokesperson told Fierce Biotech at the time, prompting the discontinuation.
