Denali, Sanofi together developing RIPK1 inhibitors for treating neurological and inflammatory diseases

Denali Therapeutics will work with Sanofi on its multiple RIPK1 inhibitor molecules that could treat a range of neurological and systemic inflammatory diseases.

In an announcement on Thursday, Denali noted that the two lead molecules DNL747 and DNL758 target a critical signaling protein known as the receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in the TNF receptor pathway, which regulates inflammation and cell death in tissues throughout the body. As Denali pointed out, the two companies plan to study DNL747 in Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis, and DNL758 in systemic inflammatory diseases such as rheumatoid arthritis and psoriasis.

According to Denali’s press release, the terms of the agreement say that Sanofi will pay to Denali $125 million upfront, and in future, along with  development and commercial milestones, payments could exceed $1 billion. Sanofi and Denali will split the profits and losses from DNL747 in the U.S. and Chinaequally, while Denali will receive a royalty from Sanofi for other territories for DNL747 and worldwide for DNL758.

Furthermore, Sanofi will pay for the first pahase, 1b and 2 clinical development costs for DNL747 for MS, ALS, and other neurological indications, while Denali will fund Alzheimer’s. Both companies will jointly split the funding of Phase 3 trials for all neurological indications, Sanofi (70%) and Denali (30%). Sanofi will fully fund the clinical development costs for DNL758 in systemic inflammatory diseases.

Rita Balice-Gordon, from Sanofi sees this collaboration as another example of “Sanofi’s commitment to accelerate the development of transformative and best-in-class treatments for patients living with serious illnesses.” 

Ryan Watts, CEO of Denali, said that  RIPK1 is a promising target with the potential to bring disease modifying medicines to patients suffering from neurodegenerative diseases as well as systemic inflammatory diseases. He said “We are very excited to partner with Sanofiand expand our RIPK1 program into new indications. With its considerable infrastructure and experience in both clinical development and commercial functions, Sanofi is an ideal partner for Denali to maximize the clinical and commercial success of our RIPK1 program.”