Lilly takes a chance on Rip kinase inhibition

Lilly has become the latest group to make a bet on Rip kinase inhibitors for autoimmune and inflammatory diseases, today licensing Rigel’s portfolio for $125m up front. The deal covers Rigel’s phase II-ready asset R552, as well as preclinical brain-penetrating Rip1 kinase inhibitors. However, the track record of other companies targeting this mechanism does not bode well. Glaxosmithkline has abandoned two projects, the Rip1-targeting GSK3145095, which had been in development for solid tumours, and the Rip2 kinase inhibitor GSK2983559, whose phase I study in inflammatory bowel disease was terminated owing to toxicology findings. Glaxo still has one shot left here with GSK2982772, in phase I for psoriasis. The other main contenders in Rip kinase inhibition are Denali and Sanofi, which are working together on the brain-penetrating project DNL788 and the peripherally acting DNL758; however, the groups discontinued their lead asset, DNL747, last June after having trouble finding a therapeutic window. Amgen also gained a Rip1 kinase inhibitor through its 2019 purchase of Nuevolution, although this does not appear to have progressed into the clinic.