Sean M. Healey & AMG Center for ALS Announces Design of TPN-101 for the Treatment of ALS in HEALEY ALS Platform Trial

The Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH) is pleased to announce the initiation of a new HEALEY ALS Platform Trial regimen design for TPN-101 in collaboration with Transposon Therapeutics, Inc.

TPN-101 was selected for inclusion in the HEALEY ALS Platform Trial by the Therapy Evaluation Committee. The HEALEY ALS Platform Trial is a multicenter, double-blind, placebo-controlled, adaptive trial for ALS. The trial's innovative design allows for efficient evaluation of multiple products simultaneously and ongoing adaptation based on emerging data. In partnership with the Northeast ALS Consortium (NEALS), the goal of the HEALEY ALS Platform trial is to accelerate the development of potential ALS therapies by testing multiple drug candidates in parallel, sharing infrastructure and improving start up and enrollment efficiencies.

TPN-101, a potent nucleoside reverse transcriptase inhibitor (NRTI), specifically inhibits the LINE-1 reverse transcriptase. Abnormal tau and TDP-43 proteins that lead to neurodegenerative diseases can increase the expression of LINE-1 transposable elements, the only retrotransposons in our genome that can become active. Increased LINE-1 expression initiates a cascade of events in the neuron that leads to neuronal dysfunction and ultimately death. In a Phase 2 clinical trial involving 42 patients with C9orf72-mutation ALS and/or frontotemporal dementia, in which the ALS population is further enriched for increased LINE-1 expression, treatment with TPN-101 was associated with reductions in key biomarkers of neuroinflammation and neurodegeneration in the ALS group. After 24 weeks of treatment, patients in the TPN-101-treated group had a 50% reduction in the rate of decline in slow vital capacity (SVC) compared with participants treated with placebo. These results provide proof-of-concept for TPN-101 in all forms of ALS associated with TDP-43 pathology.

Transposon Therapeutics, Inc., located in San Diego, Calif., is developing treatments for LINE-1 associated neurodegenerative diseases, including ALS and Alzheimer’s disease.

"We are excited to collaborate with Transposon leadership to develop their regimen for investigating TPN-101 in all people with ALS," said Merit Cudkowicz, MD, principal investigator and sponsor of the HEALEY ALS Platform Trial, director of the Sean M. Healey & AMG Center for ALS, and executive director of the Neuroscience Institute at Mass General Brigham. "We appreciate the Therapy Evaluation Committee's careful review of potential therapies for inclusion in the HEALEY ALS Platform Trial."

“We extend our gratitude to our industry partners, research collaborators, clinical trial sites and people living with ALS and their families who contribute to this rigorous and dynamic trial,” said Sabrina Paganoni, MD, PhD, co-principal investigator of the trial, physician scientist at the Healey & AMG Center, Co-Director of the Neurological Clinical Research Institute (NCRI) at MGH and Associate Professor at Harvard Medical School.

For further information about the HEALEY ALS Platform Trial please visit: HEALEY ALS Platform Trial

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 many 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.