Denali Therapeutics Announces Positive Clinical Results With Its Lead RIPK1 Inhibitor Molecule

Denali Therapeutics (NASDAQ:DNLI), a biopharmaceutical company developing a broad portfolio of product candidates for neurodegenerative diseases, today announced positive results from its Phase 1 healthy volunteer study of DNL747, a brain penetrant small molecule inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). RIPK1 is a critical signaling protein in the tumor necrosis factor receptor pathway and is a regulator of inflammation and cell death in tissues throughout the body.

As quoted in the press release:

In a randomized, double blind, placebo-controlled, oral dose study in 56 healthy subjects who received either single or multiple ascending doses or placebo, DNL747 achieved its safety, pharmacokinetic, and pharmacodynamic objectives. DNL747 was generally well tolerated with no serious adverse events at doses that achieved high levels of brain exposure and robust target engagement as measured by a blood-based biomarker of RIPK1 activity.

Denali recently announced a broad collaboration with Sanofi on the development of multiple RIPK1 inhibitor molecules, including DNL747, to study their potential to treat a range of neurological and systemic inflammatory diseases.

“The data generated in this study provides a solid foundation for rational dose selection for future clinical trials. We are excited that we are able to achieve near complete inhibition of RIPK1 activity at doses that are well tolerated in healthy subjects.  We look forward to working with our partner Sanofi to initiate patient studies in Alzheimer’s disease, ALS, and MS shortly,” said Carole Ho, M.D., Chief Medical Officer.

Click here to read the full press release.