Denali Therapeutics Inc. announced that its partner Sanofi has commenced dosing in a Phase 2 study of DNL758 (SAR443122), a peripherally-restricted small molecule inhibitor of RIPK1, in patients with cutaneous lupus erythematosus (CLE). Denali and Sanofi entered into a broad collaboration in October 2018 for the global development and commercialization of RIPK1 inhibitors. This includes peripherally restricted molecules such as DNL758 and CNS-penetrant molecules such as DNL788 (SAR443820), which is being evaluated in a Phase 1 study in healthy volunteers with potential development for neurological indications such as amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer's disease.

Under the agreement, Denali will receive a milestone payment of $15 million related to the Phase 2 study with DNL758 from Sanofi. Sanofi is responsible for the development and commercialization of DNL758 and covers all costs related to DNL758. Denali is entitled to receive development, regulatory and sales milestone payments and royalties on product sales.

RIPK1 is a critical signaling protein in the tumor necrosis factor (TNF) receptor pathway and is a regulator of inflammation and cell death. CLE is a type of interface dermatitis characterized by immune cell infiltration, and inhibition of RIPK1 activity is considered a novel approach to modulate the pathophysiology of CLE.