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.

Rip1 kinase inhibitors in clinical development 
Project Company Note
R552 Rigel Pharmaceuticals/ Lilly "Ph2 ready" for autoimmune diseases
GSK2982772 Glaxosmithkline Ph1 in psoriasis, completes Sep 2021
DNL788/SAR443820 Denali Therapeutics/ Sanofi Ph1 healthy volunteer data due H2 2021, intended for ALS, Alzheimer's & MS
DNL758/SAR443122 Denali Therapeutics/ Sanofi Ph1 in Covid-19; ph2 in cutaneous lupus erythematosus to start early 2021
Source: EvaluatePharma &

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