Triplet Therapeutics Announces Participation in Natural History Study of Myotonic Dystrophy Type 1

END-DM1 will advance understanding of disease and enable development of new biomarkers and clinical endpoints for therapeutic development

Aug. 18, 2020 10:00 UTC

END-DM1 will advance understanding of disease and enable development of new biomarkers and clinical endpoints for therapeutic development

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Triplet Therapeutics, Inc., a biotechnology company leveraging insights from the human genetics of repeat expansion disorders (REDs), today announced its participation in END-DM1 (Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1), a large international natural history study designed to advance understanding of myotonic dystrophy type 1 (DM1) and ultimately support the development of new clinical approaches to address this unmet medical need.

DM1 is one of a group of more than 50 known REDs, genetic diseases associated with expanded DNA nucleotide repeats. There are currently no available therapies that change the course of DM1 or target its underlying genetic cause. However, a significant body of human genetic evidence has revealed the key role of the DNA Damage Response (DDR) pathway, which Triplet is targeting, in driving the disease process in DM1 and other REDs. DM1, along with Huntington’s disease (HD), is a near-term focus of Triplet’s therapeutic efforts, and the first of several REDs affecting muscle that Triplet is pursuing.

“In recent years the DDR pathway has been identified as a primary driver of DM1. We are interested in learning which biomarkers change most dramatically when DNA repeats expand over time, and the clinical implications this has for patients,” said Nessan Bermingham, Ph.D., Triplet’s chief executive officer, president, and co-founder. “Understanding the answers to these questions will be beneficial in developing disease-modifying therapies that patients urgently need.”

END-DM1 is designed to:

  • Enhance understanding of patient heterogeneity by characterizing baseline status and disease progression through selected functional tests and patient-reported outcomes
  • Develop reliable biomarkers of disease severity using optimized muscle biopsy collection and analysis among a subset of patients

END-DM1 is led by Nicholas Johnson, M.D., Vice Chair of Research and Associate Professor of Neurology at Virginia Commonwealth University (VCU), and Charles Thornton, M.D., University of Rochester. The study is sponsored by VCU and the University of Rochester, and supported by the Myotonic Dystrophy Clinical Research Network (DMCRN), a network of medical centers with significant proficiency in myotonic dystrophy clinical care and research that aims to support future clinical trials of potential therapies for DM1. Other supporters include the U.S. Food and Drug Administration, the Myotonic Dystrophy Foundation, the Wyck Foundation, the Muscular Dystrophy Association, and Dyne Therapeutics.

Over the next four years, END-DM1 will enroll approximately 700 patients with DM1 aged 18-70 across eleven study sites in the U.S. and five sites in Europe.

Financial support from Triplet will facilitate overall patient enrollment and investigation of additional potential biomarkers for DM1.

Triplet also recently launched SHIELD HD ( identifier NCT04406636), an international natural history study of HD. Like END-DM1, it is designed to deepen understanding of disease progression and assess biomarkers and clinical outcomes that can support the development of new therapeutic approaches.

Studies of patient genetics have already had a dramatic impact in helping us identify the underlying causes of REDs such as DM1 and HD,” said Irina Antonijevic, M.D., Ph.D., Triplet’s chief medical officer. “We are grateful to all the patients, families, and researchers participating in END-DM1 and SHIELD HD. Both studies will be important next steps in deepening our understanding of REDs and informing future intervention trials.”

For more information about END-DM1, including study requirements and a list of participating sites, please see, identifier NCT03981575.

About Myotonic Dystrophy Type 1

Myotonic dystrophy type 1 (DM1) is a genetic disorder linked to a mutation in the DMPK gene and characterized by an increase in the number of CTG nucleotide repeats in the gene. The presence of these repeats, beyond a certain threshold, can cause a wide range of symptoms including skeletal muscle weakness and myotonia (difficulty relaxing muscles after use), cardiac dysfunction, cataracts, and other abnormalities. Thanks to the contributions of thousands of patients – whose participation in genetic research has built a fundamentally new understanding of the cause of repeat expansion disorders – it is now known that the number of CTG repeat sequences can expand over time in patients, increasing the toxic impact on cells. The DNA Damage Response (DDR) pathway plays a central role in driving this process.

About Triplet Therapeutics

Triplet Therapeutics is a biotechnology company developing transformational treatments for patients with repeat expansion disorders (REDs) – a group of more than 50 known genetic diseases including myotonic dystrophy type 1 (DM1), Huntington’s disease (HD), spinocerebellar ataxias (SCAs), fragile X syndrome, and familial amyotrophic lateral sclerosis (ALS) – leveraging insights from patient genetics. Triplet designs and develops potential therapeutics for REDs using its proprietary thRED Engine, which enables the Company to develop a single oligonucleotide targeting the DNA Damage Response (DDR) pathway to potentially treat multiple REDs.

Triplet is headquartered in Cambridge, Mass. For more information, please visit

About VCU and VCU Health

Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 30,000 students in 233 degree and certificate programs in the arts, sciences and humanities. Twenty-two of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 11 schools and three colleges. The VCU Health brand represents the VCU health sciences academic programs, the VCU Massey Cancer Center and the VCU Health System, which comprises VCU Medical Center (the only academic medical center in the region), Community Memorial Hospital, Children’s Hospital of Richmond at VCU, MCV Physicians and Virginia Premier Health Plan. For more, please visit and

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Mary Carmichael
Ten Bridge Communications

Source: Triplet Therapeutics, Inc.