Denali Therapeutics Completes Enrollment for Phase 2/3 ALS Trial of DNL343

SOUTH SAN FRANCISCO, Calif., May 01, 2024 – Denali Therapeutics Inc. (Nasdaq: DNLI), a biopharmaceutical company focused on developing treatments for neurodegenerative and lysosomal storage diseases, has announced the completion of enrollment for Regimen G of the Phase 2/3 HEALEY ALS Platform Trial. This trial is a collaborative effort between the Sean M. Healey & AMG Center and the Northeast ALS Consortium (NEALS) and evaluates the efficacy of Denali’s eIF2B agonist, DNL343.

Dr. Merit Cudkowicz, principal investigator and sponsor of the HEALEY ALS Platform Trial, expressed enthusiasm about progressing to the next phase of Regimen G. Cudkowicz, who also serves as the director of the Sean M. Healey & AMG Center for ALS and chairs the Department of Neurology at Massachusetts General Hospital (MGH), underscored the importance of the community's support and the anticipation of sharing future results.

The leadership of Regimen G features Dr. Suma Babu and Dr. Sabrina Paganoni, both key physician investigators at the Healey & AMG Center for ALS at MGH. They highlighted the completion of enrollment as a significant advancement for the HEALEY ALS Platform Trial and extended their gratitude to Denali, academic collaborators, and supporters.

Carole Ho, MD, Chief Medical Officer of Denali, celebrated this milestone in the development of DNL343. She acknowledged the critical role played by the HEALEY ALS Platform Trial investigators, their sites, and the trial participants and their families, and expressed eagerness to continue collaborating with the ALS community to advance treatment options.

DNL343 is an innovative investigational therapy targeting eIF2B, a crucial enzyme in the integrated stress response (ISR). In ALS, the ISR tends to be overactive, causing the formation of harmful stress granules that include TDP-43, a protein associated with neuronal degeneration. Laboratory studies have shown that DNL343 can inhibit the ISR, dissolve these stress granules, and reduce ISR biomarkers.

The safety and pharmacokinetics of DNL343 were evaluated in a Phase 1 study with 47 healthy participants and a Phase 1b study involving 29 ALS patients, both with up to 28 days of dosing. Results indicated that the once-daily oral administration of DNL343 was generally well tolerated and showed extensive penetration into the cerebrospinal fluid (CSF). Furthermore, a significant inhibition of ISR pathway biomarkers was observed in blood samples from the study participants. It is important to note that DNL343 remains an investigational therapy and has not received regulatory approval for commercial use.

The HEALEY ALS Platform Trial is a major collaborative initiative aimed at expediting the development of new ALS treatments. This effort, led by the Sean M. Healey & AMG Center for ALS at MGH in conjunction with NEALS, involves contributions from patients, families, clinical trial sites, industry partners, and research collaborators. The platform trial is designed to evaluate multiple investigational therapies concurrently, selected by a panel of expert ALS scientists and members of the Healey & AMG Center.

Denali Therapeutics, headquartered in South San Francisco, is a biopharmaceutical company dedicated to developing therapies for neurodegenerative and lysosomal storage diseases. The company focuses on validating genetic targets, engineering delivery mechanisms across the blood-brain barrier, and leveraging biomarkers to guide development.