Denali Therapeutics Initiates a Phase 2 Study for the RIPK1 Inhibitor DNL758 (SAR443122) in Patients with Cutaneous Lupus Erythematosus (CLE)

Denali Therapeutics partners with Sanofi.

FREMONT, CA: Denali Therapeutics Inc. (NASDAQ: DNLI), a biopharmaceutical company developing a broad pipeline of product candidates engineered to cross the blood-brain barrier (BBB) for neurodegenerative diseases, collaborates with Sanofi. Their partnership begins dosing patients with cutaneous lupus erythematosus in a Phase 2 study of DNL758 (SAR443122), a peripherally restricted small molecule inhibitor of RIPK1 (CLE).

“We are delighted that our collaborators at Sanofi are advancing DNL758 into a Phase 2 study in patients with CLE and are excited about the potential of bringing a life-changing therapy to patients through our partnership,” says Ryan Watts Ph.D., Denalis Chief Executive Officer.

In October 2018, Denali and Sanofi announced a broad collaboration for the global development and commercialization of RIPK1 inhibitors. 

This includes peripherally restricted molecules such as DNL758 and CNS-permeable molecules such as DNL788 (SAR443820), which is currently being evaluated in healthy volunteers in a Phase 1 study for the potential development of neurological indications such as amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's disease. Denali will receive a $15 million milestone payment from Sanofi in connection with the Phase 2 study with DNL758. Sanofi is responsible for the development and commercialization of DNL758 and is financially responsible for all associated costs. Denali is entitled to receive milestone payments for product development, regulatory approval, and sales, as well as royalties on product sales.

RIPK1 is an essential signaling protein in the tumor necrosis factor (TNF) receptor pathway that plays a role in inflammation and cell death regulation. CLE is a type of interface dermatitis characterized by immune cell infiltration, and inhibiting RIPK1 activity is a novel strategy for modulating CLE pathophysiology. Additional information about the Phase 2 clinical study of DNL758 for CLE (NCT04781816) can be found on the ClinicalTrials.gov website.