Sanofi pays $125 million for Denali’s RIPK1 programs

In another sizable deal for Denali Therapeutics, Sanofi is paying $125 million to buy into a series of neuroinflammation compounds called RIPK1 inhibitors. The pact provides key funding for the molecules, which have potential activity across several diseases with large patient populations, including Alzheimer’s, multiple sclerosis, and arthritis.

The deal will allow Denali to expand the therapeutic scope of its RIPK1 inhibitors, which block an enzyme implicated in cell death and inflammation. The biotech firm is wrapping up Phase I studies of DNL747, a brain-penetrating RIPK1 inhibitor, in healthy volunteers and expects to soon test the compound in people with Alzheimer’s disease and amyotrophic lateral sclerosis.

Sanofi will also explore the compound’s use in multiple sclerosis. It will later lead and pay for 70% of the cost of Phase III development across all diseases.

“Our development costs for RIPK1 overall are largely covered,” says Denali Chief Operating Officer Alexander Schuth.

Denali was created by former Genentech executives to reinvigorate the field of neurodegeneration. Since emerging from stealth in May 2015, the biotech has raised buckets of cash—nearly $350 million across two venture rounds, $250 million in a public offering, and $125 million in a deal with Takeda Pharmaceutical—to support that mission. Today the firm has a staff of 175, including 100 discovery scientists

That cash has also allowed Denali to buy interesting assets, such as earlier RIPK1 compounds that came through its 2016 acquisition of Incro Pharmaceuticals, a biotech firm based on discoveries by Harvard Medical School’s Junying Yuan. Yuan found that in addition to unprogrammed apoptosis, cells undergo programmed death via the TNF pathway, which is in part mediated by RIPK1.

Her group later developed a small-molecule inhibitor of the enzyme. Denali discontinued a Phase I study of Yuan’s molecule, DNL104, because of liver toxicity, Schuth says, but its scientists went on to develop DNL747 and DNL758, which was designed for systemic use.