Denali Therapeutics, a neurodegenerative diseases specialist, on Tuesday brought to public 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), which 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.
Denali said that DNL747 met safety, pharmacokinetic, and pharmacodynamic goals in the study.
Denali is collaborating 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.
Carole Ho, Chief Medical Officer at Denali said that 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,”she said.
In addition to DNL747, Denali Therapeutics in its press release reminded that, together with Sanofi, it is pursuing several other compounds, including DNL758, a RIPK1 inhibitor acting peripherally without meaningful blood-brain barrier penetration, for systemic inflammatory diseases. The San Francisco based company added that Sanofi plans to initiate clinical trials with DNL758 in 2019.