Denali Therapeutics to present DNL343 Phase 1b data at AAN annual meeting

Denali Therapeutics announced that new data from the 28-day treatment period of the Phase 1b study of DNL343 in participants with amyotrophic lateral sclerosis will be presented at the 75th Annual Meeting of the American Academy of Neurology, which will be held April 22-27, 2023, in Boston, Massachusetts. DNL343 is an investigational, small molecule eIF2B activator designed to cross the BBB with the potential of preventing or slowing ALS disease progression. The DNL343 abstract is available here on the AAN conference website. A PDF of the poster presentation will be made available on Denali’s website under the Events section here after the AAN poster session begins at 11:45 a.m. EDT on April 25, 2023. As previously announced, DNL343 has been selected to enter the Phase 2/3 HEALEY ALS Platform Trial; Denali expects that recruiting will begin in mid 2023. Denali previously announced initial interim Phase 1b results after 20 participants who had been randomized to receive DNL343 or placebo had completed the double-blind period of the study. The data demonstrated that once-daily oral dosing with DNL343 for 28 days was generally well-tolerated and was associated with extensive distribution in the cerebrospinal fluid as well as robust inhibition of biomarkers associated with the integrated stress response as measured by CHAC1 gene expression and ATF4 protein levels in blood samples from study participants. The Phase 1b pharmacokinetic profile along with preclinical in vivo data are consistent with extensive distribution of DNL343 in the central nervous system. The upcoming presentation at AAN will include data from all 29 participants with ALS from the randomized, placebo-controlled, 28-day treatment period of the Phase 1b study. The results remain consistent with those previously reported as described above.