Solid’s nNOS microdystrophin is a unique 5-repeat construct that includes the neuronal nitric oxide synthase (nNOS) binding domain, responsible for protection against ischemia-induced muscle injury by maintaining nitric oxide (NO) signaling at the muscle sarcolemma. It is intended to act as a functional surrogate for dystrophin when administered to patients with Duchenne muscular dystrophy (DMD). Initial clinical evaluation of nNOS microdystrophin was performed in the IGNITE DMD Phase 1/2 study using a first-generation gene therapy vector, SGT-001, which delivered the transgene using an AAV9 capsid. Nine subjects were administered a single systemic infusion of SGT-001, with the first 3 receiving 5E13 vg/kg and the next 6 dosed at 2E14 vg/kg. Three untreated subjects were also enrolled in the study and analyzed as controls. Safety and efficacy were evaluated throughout the study, with a primary endpoint of 1 year and a 5-year long-term follow up period.
Data previously presented up to 2 years post-treatment in the 2E14 vg/kg cohort subjects demonstrated sustained expression of functional microdystrophin, localization of nNOS to the membrane, and stable or improved function. All AEs and SAEs previously reported to have occurred in the first weeks following dosing resolved without sequalae and no new drug-related safety findings have been reported in any patients.
We now present data up to 3 years post-dosing demonstrating the durability of treatment effect. Subjects receiving 2E14 vg/kg maintained motor function (NSAA, 6MWT), pulmonary function (FVC %predicted), and PROMs (PODCI) compared against expected natural history declines. These results continue to suggest the potential for the expression of Solid’s differentiated nNOS microdystrophin to confer meaningful clinical benefit to patients with DMD. Solid’s next generation gene therapy program, SGT-003, will build on these results to deliver the nNOS microdystrophin construct using a novel capsid designed to enhance muscle-targeted delivery and lower the dose level.