Sanofi & Denali Therapeutics to Develop Multiple Molecules; $125 Million Upfront

Sanofi plans to collaborate with Denali Therapeutics Inc. on the development of multiple molecules with the potential to treat a range of neurological and systemic inflammatory diseases.

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. The companies plan to study DNL747 in multiple sclerosis (MS), Alzheimer’s disease, and amyotrophic lateral sclerosis (ALS), and DNL758 in systemic inflammatory diseases such as rheumatoid arthritis and psoriasis.

Under the terms of the agreement, Sanofi will make an upfront cash payment to Denali of $125 million, with future development and commercial milestone payments that could exceed $1 billion. Sanofi and Denali will share commercial profits and losses from DNL747 in the U.S. and China equally, while Denali will receive a royalty from Sanofi for other territories for DNL747 and worldwide for DNL758.

Phase 1b and 2 clinical development costs for DNL747 will be fully funded by Sanofi for MS, ALS, and other neurological indications, except in Alzheimer’s disease, which will be funded by Denali. Phase 3 trials for all neurological indications will be jointly funded by Sanofi (70%) and Denali (30%). Sanofi will fully fund the clinical development costs for DNL758 in systemic inflammatory diseases.

 “This collaboration with Denali is yet another example of Sanofi’s commitment to accelerate the development of transformative and best-in-class treatments for patients living with serious illnesses,” said Rita Balice-Gordon, PhD, Global Head of Rare and Neurologic Diseases Research at Sanofi. “We look forward to working with Denali on the RIPK1 program as we explore the potential of this mechanism in neurologic and inflammatory diseases.”

 “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. We are very excited to partner with Sanofi and expand our RIPK1 program into new indications,” added Ryan Watts, PhD, CEO of Denali. “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.”

 RIPK1 Molecules

-DNL747, a brain-penetrant small molecule, is currently being evaluated in early clinical stage trials, known as Phase 1. Phase 1b studies in Alzheimer’s disease and ALS patients are expected to commence in the near-term and will inform the subsequent clinical development. Denali will lead the Phase 2 clinical trials in Alzheimer’s disease while Sanofi will lead the Phase 2 clinical trials in MS and ALS, as well as future Phase 3 trials in all neurological indications.
-DNL758 is a small molecule that does not penetrate the brain. Sanofi will lead clinical development activities for all systemic inflammatory diseases. The clinical trials are expected to begin in 2019.

The collaboration also includes additional pre-clinical RIPK1 inhibitor molecules.  The transaction is expected to close in the coming months in accordance with customary regulatory approvals.