San Francisco — Epicrispr Biotechnologies announced interim results from an ongoing Phase 1/2 clinical trial showing increased lean muscle volume in the first three evaluable patients with facioscapulohumeral muscular dystrophy treated with its investigational therapy EPI-321.
The company said the findings represent the first reported clinical evidence of increased muscle volume following treatment in patients with FSHD, a progressive neuromuscular disease that causes ongoing muscle degeneration and weakness. There are currently no approved therapies for the condition.
As of the May 12 data cutoff, nine patients had received a single intravenous infusion of EPI-321 across two dose cohorts. Six patients were treated at a dose of 2×10¹³ vg/kg, while three received 4×10¹³ vg/kg.
Epicrispr said the therapy demonstrated a positive safety profile, with no serious adverse events reported.
All three evaluable patients in the first cohort showed gains in lean muscle volume six months after treatment compared with baseline. The average increase was about 370 milliliters, equivalent to approximately 0.8 pounds of muscle mass. Individual gains ranged from about 0.5 to 1.3 pounds, with some muscles showing increases of 15%.
“These results represent a major scientific breakthrough for both the FSHD community and the field of epigenetic medicine,” said Amber Salzman, Ph.D., Chief Executive Officer, Epicrispr Biotechnologies. “For the first time, we are seeing clinical evidence that a therapy may suppress the genetic driver of FSHD and increase muscle volume. The alignment between imaging, biomarker, and functional data strengthens our confidence in the potential of EPI-321 to meaningfully alter the course of disease.”
EPI-321 is designed to silence DUX4, the genetic driver of FSHD, using Epicrispr’s Gene Expression Modulation System platform. The single-dose therapy is intended to regulate disease-causing gene expression without changing the underlying DNA sequence.
The company said MRI findings were supported by reductions in a circulating cell-free DNA biomarker associated with DUX4 pathway activity. The results were also consistent with previously reported favorable trends in strength and functional measures at three months.
“Patients with FSHD face a lifelong, progressive loss of muscle that can affect nearly every aspect of daily living, from walking and climbing stairs to maintaining independence,” said Russell Butterfield, M.D., Principal Study Investigator and Associate Professor in Pediatrics & Neurology, University of Utah. “Historically, we have had very limited ability to alter the course of the disease. Although these are early results and additional follow-up is needed, the observed changes in lean muscle volume are encouraging and suggest EPI-321 may be addressing the underlying drivers of disease in a way that could ultimately translate into meaningful benefit for patients.”
MRI analyses were conducted with Springbok Analytics, whose artificial intelligence-powered platform measures muscle volume and other biomarkers from whole-body MRI scans.
“The consistency of the MRI findings across all evaluable patients was remarkable, particularly in a disease where muscle deterioration is expected over time,” said Silvia Blemker, Ph.D., Chief Scientific Officer, Springbok Analytics. “Our quantitative whole-body MRI and AI-powered muscle analysis, enabled objective assessment of changes in lean muscle volume across up to 140 individual muscles throughout the body. While these are early results, the data highlight the value of advanced imaging in capturing treatment-related changes that may not be apparent through traditional clinical assessments.”
The ongoing study is evaluating the safety, tolerability, biological activity and preliminary efficacy of EPI-321 in adults with FSHD. Epicrispr expects to present additional data at the World Muscle Society Annual Congress in September and complete the primary portion of the trial in mid-2027.
