The HEALEY ALS Platform Trial completes enrollment for Regimen G evaluating investigational product DNL343 from Denali Therapeutics

BOSTON – The Sean M. Healey & AMG Center for ALS in collaboration with the Northeast ALS Consortium (NEALS) is thrilled to announce the completion of enrollment for Regimen G of the HEALEY ALS Platform Trial. This marks the  seventh regimen to complete enrollment since the 2020 launch of the first of its kind clinical trial for amyotrophic lateral sclerosis (ALS). The trial is designed to evaluate multiple investigational products simultaneously, thus accelerating the development of effective and breakthrough treatments for people living with ALS.

Regimen G of the HEALEY ALS Platform Trial evaluates investigational product DNL343 from Denali Therapeutics. Denali is a biotechnology company based in South San Francisco, California, and DNL343 is not yet approved for use in any country. 

The conclusion of enrollment for DNL343 signifies a pivotal step forward in our research to find effective treatments for ALS,” said Merit Cudkowicz, MD, MSc, principal investigator and sponsor of the HEALEY ALS Platform Trial, director of the Sean M. Healey & AMG Center for ALS, chair of the Department of Neurology at MGH, and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “We look forward to evaluating the effects of this investigational product and sharing our findings with the ALS community.”

Investigational product candidates that enter the platform trial are selected by a group of expert ALS scientists and members of the Platform Trial Therapy Evaluation Committee.

DNL343 is a novel investigational ALS therapy that targets eIF2B, a central regulator of the integrated stress response (ISR). The ISR appears to be overactive in ALS, leading to the formation of stress granules containing TDP-43. Buildup of TDP-43 is harmful and leads to neuronal degeneration. In the lab, inhibition of the ISR by DNL343 dissolves TDP-43 containing stress granules and decreases ISR biomarkers. The safety, pharmacokinetics, and pharmacodynamics of DNL343 have been characterized in both healthy participants and people with ALS, in a Phase 1 (N=47) and a Phase 1b (N=29) study, respectively, with dosing for up to 28 days. Results from both studies demonstrated that once-daily oral dosing with DNL343 was generally well tolerated and exhibited extensive Cerebrospinal Fluid (CSF) penetration. In addition, robust inhibition of biomarkers associated with the ISR pathway was observed in blood samples from study participants.

Regimen G is co-led by Suma Babu, MBBS, MPH, and Sabrina Paganoni, MD, PhD, physician investigators at the Healey & AMG Center for ALS at MGH.

“We are grateful for our ALS participants and their families for their commitment to research and investigation of DNL343 and other experimental products” said Drs. Paganoni and Babu. “Along with our academic collaborators, founders, industry partners and benefactors of the platform trial, the robust research we conduct would not be possible without the partnership of our patient community.”

For updates on the trial, please join our weekly Healey ALS Platform webinars.

Watch this video for more information on the mechanism of action behind DNL343 from Denali Therapeutics.

About the Sean M. Healey & AMG Center for ALS at Mass General

At the Sean M. Healey & AMG Center for ALS at Mass General, we are committed to bringing together a global network of scientists, physicians, nurses, foundations, federal agencies, and people living with ALS, their loved ones, and caregivers to accelerate the pace of ALS therapy discovery and development.

Launched in November 2018, the Healey & AMG Center, under the leadership of Merit Cudkowicz, MD and a Science Advisory Council of international experts, is reimagining how to develop and test the most promising therapies to treat the disease, identify cures and ultimately prevent it.

With dozens of active clinical trials and lab-based research studies in progress right now, we are ushering in a new phase of ALS treatment and care. Together, we will find the cures.