Denali Therapeutics announces DNL343 interim Phase 1b data in ALS

Denali Therapeutics announced interim results from a Phase 1b study of its eIF2B agonist, DNL343, in participants with amyotrophic lateral sclerosis. Once-daily oral dosing with DNL343 for 28 days was generally well tolerated and demonstrated extensive BBB penetration as well as robust inhibition of biomarkers associated with the integrated stress response in blood samples from study participants. By inhibiting the ISR pathway, DNL343 is intended to prevent or slow disease progression associated with stress granule formation and TDP-43 aggregation, a hallmark pathology present in nearly all individuals with ALS. Denali also announced initiation of the design phase of a Phase 2/3 study for entry into the HEALEY ALS Platform Trial led by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital in collaboration with the Northeast ALS Consortium. "These initial Phase 1b results with DNL343 in ALS are consistent with our previously reported Phase 1 healthy volunteer data and are an important milestone for the program," said Carole Ho, M.D., Chief Medical Officer at Denali. "The data continue to support late-stage development plans for DNL343, and we are excited to be collaborating with the HEALEY ALS Platform Trial team in our unified effort to advance potential treatment options for people living with ALS."