The original 2021 agreement had Lilly leading clinical development and potential commercialization of brain-penetrating RIPK1 inhibitors, while Rigel conducted preclinical CNS-penetrant RIPK1 programs at that time.

Despite the CNS-focused termination, the broader collaboration persists because the core asset ocadusertib, a RIPK1 inhibitor, remains part of the deal, with Lilly moving it into a Phase 2 trial for adults with moderately to severely active rheumatoid arthritis, keeping milestone payments within Rigel’s reach.

Lilly has terminated the CNS-focused portion of the $960 million biobucks collaboration with Rigel centered on RIPK1 inhibitors for CNS diseases, effective after notifying Rigel in early October.

RIPK1 inhibitors continue to generate interest given RIPK1’s role in programmed cell death and inflammation, with activity across the field including Novartis taking an option on Sironax’s BBB-crossing platform and Sanofi’s exit from a RIPK1 program after a midphase MS study failure with Denali Therapeutics.

Ocaduzustertib is a phase 2-ready RIPK1 inhibitor and was the key asset of the pact, valued at up to $835 million in milestones in addition to a $125 million upfront.