Benzinga | Oct 7, 2021 06:52AM EDT

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

* Denali Therapeutics Inc (NASDAQ: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 (NASDAQ: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.