The companies will also jointly work on the development of a separate possible therapy, DNL758, for systemic inflammatory diseases such as rheumatoid arthritis and psoriasis.
Both DNL747 and DNL758 are small molecule inhibitors of a protein known as RIPK1 (receptor-interacting serine/threonine-protein kinase 1), which is involved in the tumor necrosis factor (TNF) receptor pathway that is implicated in inflammation, immunity, and cell death. DNL747 and DNL758 are the lead investigative molecules of the company’s RIPK1 inhibitor program.
DNL747 is able to cross the blood-brain barrier (BBB) and reach the brain. It is now being studied in Phase 1 trials, with Phase 1b studies in amyotrophic lateral sclerosis (ALS) and Alzheimer’s set to start soon. Denali will head and fund Phase 2 trials in Alzheimer’s, with Sanofi leading and fully funding Phase 2 studies in MS and ALS. All potential Phase 3 studies will be funded by both Sanofi (70%) and Denali (30%).
In turn, clinical studies with DNL758 (which does not penetrate the BBB) will be wholly funded and led by Sanofi, and are expected to begin in 2019.
“We look forward to working with Denali on the RIPK1 program as we explore the potential of this mechanism in neurologic and inflammatory diseases,” Rita Balice-Gordon, PhD, Sanofi’s global head of rare and neurologic diseases research, said in a press release.
According to Balice-Gordon, the collaboration with Denali illustrates Sanofi’s commitment “to accelerate the development of transformative and best-in-class treatments for patients living with serious illnesses.”
Ryan Watts, PhD, Denali’s CEO, added: “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.”
Watts believes that Sanofi’s infrastructure and experience makes it an ideal partner in advancing Denali’s RIPK1 program.
The agreement also includes an upfront cash payment from Sanofi to Denali of $125 million, and potential future development and commercial milestone payments that could surpass $1 billion. Distribution of profits or losses, as well as royalties, by Sanofi to Denali were also defined. The transaction is expected to be finalized in the coming months.