Update on the INSPIRE DUCHENNE Phase 1/2 Study of the Next-Generation Microdystrophin Gene Therapy Candidate SGT-003 for Duchenne Muscular Dystrophy

Topic:

Clinical Trials

Poster Number: 441 O

Author(s):

Aravindhan Veerapandiyan, MD, Arkansas Children's Hospital, Kevin Flanigan, MD, Nationwide Children's Hospital, Eugenio M. Mercuri, MD, Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Rome, Italy, Craig McDonald, MD, Department of Physical Medicine and Rehabilitation, University of California Davis, CA, USA, Perry Shieh, MD, University of California Los Angeles, Hernan Gonorazky, MD, SickKids, Crystal Proud, MD, Children’s Hospital of the King’s Daughters, Norfolk, VA, USA, Craig M. Zaidman, MD, Department of Neurology, Washington University in St Louis, St Louis, MO, USA, Alicia Henriquez, MD, Seattle Children's Hospital, Patrick Gonzalez, PhD, Solid Biosciences, Matthew Harmelink, MD, Solid Biosciences, Gabriel Brooks, MD, Solid Biosciences

INSPIRE DUCHENNE is a Phase 1/2, open-label, first-in-human clinical trial evaluating the safety, tolerability, and efficacy of a single intravenous infusion of SGT-003 in patients with Duchenne muscular dystrophy. SGT-003 is Solid’s next-generation AAV-based microdystrophin gene therapy candidate. SGT-003 utilizes the novel AAV-SLB101 muscle-tropic capsid, which has demonstrated more rapid and higher levels of biodistribution and expression in muscle tissues, along with reduced biodistribution to the liver, in non-clinical studies compared to first generation capsids. SGT-003 microdystrophin uniquely includes the R16/R17 binding domain that stabilizes critical signaling proteins, such as nNOS, at the sarcolemma to restore additional full-length dystrophin protein functionality compared to earlier approaches.

As of a December 15, 2025 data cut, SGT-003 has been administered to 32 study participants ranging from 1 to 10 years of age and up to approximately 40 kg in weight. As of the data cut, SGT-003 has generally been well tolerated with the most frequent treatment-related adverse events being nausea, vomiting, and loss of appetite. Thrombocytopenia was observed at a higher frequency in early trial participants but has decreased following updates to the prophylactic steroid regimen. Muscle biopsy analyses from 10 participants reaching the Day 90 timepoint and 2 participants reaching the Day 360 timepoint demonstrated high vector genome copies with robust and durable microdystrophin expression. Biomarkers evaluating muscle integrity showed consistent, sustained improvements at Day 90, Day 180, and Day 360. To date, the safety and biomarker profile of SGT-003 remain encouraging, with improvements in markers of muscle integrity observed out to Day 360 post-dosing.

Additional updates on this study and the SGT-003 program will be provided at the time of presentation.