Denali Highlights Encouraging Early Data, Update For Amyotrophic Lateral Sclerosis Program

Denali Therapeutics Inc DNLI announced data from the Phase 1 trial evaluating DNL343, eIF2B activator, in 95 healthy volunteers.
DNL343 was generally well tolerated for up to 14 days of dosing, with robust distribution in the central nervous system and predictable dose-related increases in DNL343 exposure with a PK profile supporting once-daily dosing.
Blood samples of healthy volunteers were subjected to stress ex vivo, and robust changes in biomarkers of the ISR were observed.
The integrated stress response (ISR) is a biological pathway implicated in amyotrophic lateral sclerosis (ALS) and other diseases.
Denali also presented preclinical data in a mouse model of vanishing white matter disease.
DNL343 treatment normalized body weight and motor function. ISR gene expression and stress response protein levels were reduced in peripheral tissues and the brain.
The company is conducting Phase 1b trial to evaluate the safety, PK, and PD of DNL343 in approximately 30 participants with ALS.
Denali's partner Sanofi SA SNY plans to initiate a Phase 2 study of RIPK1 inhibitor SAR443820 in ALS participants in Q1 of 2022.
The Phase 2 HIMALAYA trial, followed by an open-label long-term extension, will evaluate the efficacy and safety of SAR443820.
Related: Denali's Brain-Penetrant Enzyme Therapy Shows Durable Effect With CNS Impact In Hunter Syndrome.
Price Action: DNLI stock closed 0.60% lower at $49.98 on Wednesday.