RIPK1

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a critical signaling protein implicated in a broad range of key inflammatory cellular processes.

RIPK1 inhibition has therapeutic potential in treating autoimmune, inflammatory, and neurodegenerative disorders.

Ocadusertib (previously LY3871801/R552), an oral, potent, and selective inhibitor of RIPK1, discovered by Rigel's Research team, is being developed for the treatment of autoimmune and inflammatory disorders by Eli Lilly. In preclinical studies, R552 demonstrated prevention of joint and skin inflammation in a RIPK1-mediated murine model of inflammation and tissue damage.

Pursuant to the collaboration, Lilly is also leading preclinical and clinical development of brain-penetrating RIPK1 inhibitors in central nervous system (CNS) diseases. In early October, Rigel received notification from Lilly that it will terminate the CNS disease program, which will become effective 60 days following notification.

Development of ocadusertib:

• A Phase 2a trial (NCT05848258) in adult patients with active moderately to severely rheumatoid arthritis (RA) is being led by partner Eli Lilly.

Development CNS-penetrating RIPK1 inhibitors:

• Currently in preclinical studies