Eli Lilly and Co. and Rigel Pharmaceuticals, Inc. entered an exclusive global license agreement and strategic collaboration to co-develop and commercialize Rigel’s R552, a receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitor, for all indications including autoimmune and inflammatory diseases. Lilly will also lead all clinical development of brain penetrating RIPK1 inhibitors in central nervous system (CNS) diseases.
 
Rigel’s lead RIPK1 inhibitor, R552, has will begin Phase 2 clinical trials in 2021 as part of the collaboration. Rigel also has ongoing preclinical activities with its lead CNS penetrant RIPK1 inhibitor candidates. In preclinical studies, Rigel’s R552 demonstrated prevention of joint and skin inflammation in a RIPK1-mediated murine model of inflammation and tissue damage.
 
Lilly will pay $125 million upfront and up to $835 million in potential development, regulatory, and commercial milestones, as well as royalties depending on Rigel’s clinical development investment. Lilly and Rigel will co-develop R552 at specified contribution levels. Lilly will be responsible for all costs of global commercialization for R552, and Rigel will have the right to co-commercialize R552 in the U.S. Lilly will be solely responsible for all clinical development and commercialization of brain penetrating RIPK1 inhibitors in CNS indications.
 
RIPK1 is a critical signaling protein implicated in a broad range of key inflammatory cellular processes including necroptosis, a type of regulated cell death, and cytokine production. In necroptosis, cells rupture leading to the dispersion of cell contents which can trigger an immune response and enhance inflammation. Inhibiting RIPK1 may be a new approach to treating various autoimmune, inflammatory, and neurodegenerative disorders.
 
This transaction is subject to customary closing conditions.