Adeno-associated virus (AAV) vectors are a promising tool for gene therapy due to their ability to deliver genetic material with high precision. However, high systemic doses currently required to achieve widespread therapeutic benefit for neuromuscular indications can pose potential safety risks, including acute serious liver injury. To address this issue, capsids can be engineered to refine and enhance their tropism to tissues of interest, while de-targeting the liver. AAV-SLB101, Solid Biosciences’ proprietary, rationally designed capsid, has shown increased skeletal and cardiac muscle tropism and decreased biodistribution to the liver in preclinical studies. Solid’s next-generation, investigational gene therapy, SGT-003, developed for the treatment of Duchenne muscular dystrophy, utilizes the AAV-SLB101 capsid to better target muscle using a lower dose with the goal of improving upon the liver toxicity profile observed in products using other AAV vectors.
As of December 15, 2025, SGT-003 has been generally well tolerated, demonstrating a favorable safety profile with no findings of drug-induced liver injury, across the 32 total participants who have received SGT-003 in the Phase 1/2 INSPIRE DUCHENNE trial (NCT06138639). Importantly, ALT and AST have generally remained below their normally high baseline levels, due to impaired muscle membrane integrity, post-treatment and have remained low over time. GGT, an important marker of liver injury, remained stable across participants through at least 90 days post-treatment.
These findings suggest that the positive liver safety profile observed following SGT-003 administration may be attributed to AAV-SLB101’s reduced liver biodistribution and may represent a differentiated profile compared to other systemic gene therapies that have resulted in more frequent liver injury and liver failure.