お知らせ • Mar 12
Solid Biosciences Inc. Provides Interim Positive Clinical Update on Phase 1/2 Inspire Duchenne Trial
Solid Biosciences Inc. reported updated positive interim data from the ongoing Phase 1/2 INSPIRE DUCHENNE clinical trial of SGT-003. The new data, including additional muscle biopsy, serum biomarker, cardiac function, and safety analyses, add to a growing dataset that suggests the potential of the biological activity of SGT-003 microdystrophin therapy. INSPIRE DUCHENNE is a Phase 1/2 first-in-human, open-label, single-dose, multicenter trial designed to evaluate the safety, tolerability and efficacy of SGT-003 in pediatric participants with Duchenne at a dose level of 1E14vg/kg. SGT-003 is administered as a one-time intravenous infusion. The interim clinical data reported in this release are as of a February 23, 2026, data cutoff date. SGT-003 has been generally well tolerated in the 40 participants dosed as of March 11, 2026. The safety and tolerability profile observed in the INSPIRE DUCHENNE trial continued to be promising; SGT-003 is administered using a low-burden, steroid-only prophylactic immunomodulation regimen. The trial is being conducted at 15 clinical sites across the US, Canada, Italy and the United Kingdom and participant dosing remains ongoing. Microdystrophin transduction and expression levels, beta-sarcoglycan localization and nNOS activity were evaluated by biopsy in 20 participants (ages 1-10 years) at Day 90 and in 3 participants at Day 360. Results demonstrated robust mean vector copies per nucleus and microdystrophin expression as well as properly localized and restored beta-sarcoglycan-positive fibers and nNOS activity-positive fibers. Beta-sarcoglycan and nNOS are critical components of the dystrophin-associated protein complex (DAPC). In Duchenne, the absence of dystrophin destabilizes the DAPC, triggering a cascade of structural, signaling and metabolic defects that impair muscle integrity. Reconstituting critical components of the DAPC, including beta-sarcoglycan and nNOS, could suggest biologic correlation of SGT-003’s treatment effect. Solid’s microdystrophin construct is the only microdystrophin gene therapy, approved or investigational, that contains the R16/R17 binding domain, which uniquely localizes nNOS to the muscle. Table 1: 90- and 360-day biopsy results: Day 90 (n=20 unless noted), Day 360 (n=3). Mean vector copies per nucleus: 11 (Day 90), 12 (Day 360). Mean microdystrophin expression by western blot (%): 60% (n=19) (Day 90), 91% (Day 360). Mean microdystrophin expression by mass spectroscopy (%): 52% (n=17) (Day 90), 86% (Day 360). Mean microdystrophin-positive fibers by immunofluorescence (%): 63% (Day 90), 69% (Day 360). Properly localized and restored beta-sarcoglycan-positive fibers (%): 60% (Day 90), 69% (Day 360). nNOS activity-positive fibers (%): 35% (Day 90), 33% (Day 360). Western blot and mass spectrometry baselines were 0% mean normal dystrophin, microdystrophin-positive fibers by immunofluorescence was based on a manual count, as are beta-sarcoglycan and nNOS-positive fibers. These assays are conducted by multiple external vendors; at the time of analysis, one western blot sample and three mass spectrometry samples had not been received. Additionally, Solid has identified an extensive biomarker panel to comprehensively evaluate treatment effect on muscle integrity. Collectively, these observed biomarker improvements at Day 90 and Day 360 suggest improved muscle fiber health and stability, reduced ongoing muscle damage, and an interruption of the chronic degeneration/regeneration cycle that is characteristic of Duchenne. In particular, embryonic myosin heavy chain (eMHC) is an informative predictor of disease progression. eMHC is typically expressed during fetal development but is also expressed when muscle satellite cells differentiate into muscle fibers, which in Duchenne occurs in response to muscle fiber damage. In the absence of functional dystrophin, newly generated muscle fibers also fail, leading to continued but ultimately futile satellite cell activation. A mean 44% observed reduction in eMHC positive fibers seen at Day 90 (n=20) suggests that SGT-003 treatment has potentially disrupted this chronic and futile degeneration-regeneration cycle, stabilizing muscle fibers and preserving the reservoir of satellite cells. Table 2: Improvements in multiple biomarkers of muscle integrity observed at Day 90 and Day 360. Serum Biomarkers: Day 90 Mean Reductions (n=24 unless noted), Day 360 Mean Reductions (n=7 unless noted). Serum creatine kinase (CK): 38% (Day 90), 37% (Day 360). Serum alanine transaminase (ALT): 43% (Day 90), 27% (Day 360). Serum aspartate aminotransferase (AST): 30% (Day 90), 32% (Day 360). Serum lactate dehydrogenase (LDH): 46% (n=21) (Day 90), 38% (n=6) (Day 360). Serum titin: 22% (n=11) (Day 90), 25% (n=2) (Day 360). Certain data from a subset of participants were not available at the time of analysis. While cardiac assessments were initially included as safety evaluations, stabilization-to-improvement in systolic function continues to be observed as of the data cutoff date, as measured by left ventricular ejection fraction (LVEF). Observed improvements were driven largely by participants with low-normal baseline LVEF (defined as = 60%). Cardiomyopathy is a leading cause of death in Duchenne, with 25% of individuals displaying evidence of cardiomyopathy by six years of age, increasing to 59% by 10 years of age. SGT-003 is an investigational gene therapy containing a differentiated microdystrophin construct and a proprietary, next-generation capsid, POLARIS-101™ (formerly known as AAV-SLB101), which was rationally designed to target integrin receptors, and has shown enhanced cardiac and skeletal muscle transduction with decreased liver targeting in data from the Phase 1/2 INSPIRE DUCHENNE clinical trial and in nonclinical studies. SGT-003’s microdystrophin construct uniquely includes the R16/17 domains, which localize nNOS to the muscle. Nonclinical studies have shown that nNOS can improve blood flow to the muscle thereby reducing muscle breakdown from ischemia and muscle fatigue. Together, these design features suggest that SGT-003 could be a potential best-in-class investigational gene therapy for the treatment of Duchenne. INSPIRE DUCHENNE is a first-in-human, open-label, single-dose, multicenter Phase 1/2 clinical trial to evaluate the safety, tolerability and efficacy of SGT-003 in pediatric participants with a genetically confirmed Duchenne diagnosis with a documented dystrophin gene mutation. INSPIRE DUCHENNE is a multinational trial designed to enroll participants in the United States, Canada, the United Kingdom and Italy. IMPACT DUCHENNE is a Phase 3 randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of SGT-003 in ambulatory participants aged 7 to less than 12 with a genetically confirmed Duchenne diagnosis. IMPACT DUCHENNE is a multinational trial intended to support potential regulatory authorizations.