Solid’s Next-Generation DMD Gene Therapy Cleared for First-in-Human Trial

January 4, 2024

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The AAV-SLB101 capsid used in SGT-003 may yield increased transgene expression and improved safety compared with first-generation AAV gene therapies.

The FDA has cleared Solid Biosciences’ investigational new drug clearance (IND) for a phase 1/2 trial of its Duchenne muscular dystrophy gene therapy SGT-003.¹

“We are pleased to have the FDA’s clearance to proceed into the clinic with SGT-003, a new, innovative gene therapy candidate for Duchenne,” Bo Cumbo, president and chief executive officer, Solid Biosciences, said in a statement.¹ “SGT-003 combines our differentiated microdystrophin transgene with a next generation muscle-tropic capsid and a transient transfection manufacturing process that may help address the unmet needs for the Duchenne community.”

Solid is expecting to soon submit the planned SGT-003-101 trial for institutional review board approval at the clinical trial sites and then commence patient screening. The trial will be a first-in-human, multicenter, open-label trial that will assess the safety and tolerability of a single, 1E14 vg/kg dose of SGT-003 in pediatric patients with DMD. The trial has 2 planned cohorts of at least 3 patients each; patients will be aged at least 4 and under 6 years in cohort 1. Patients will be evaluated for long-term safety and efficacy for 5 years after treatment in the trial.

“We appreciate the FDA’s review of the IND and look forward to continuing to work in collaboration with the agency when we initiate dosing of DMD patients,” Jessie Hanrahan, PhD, chief regulatory officer, added to the statement.¹

SGT-003 uses the company’s proprietary AAV-SLB101 capsid to deliver an encoded microdystrophin protein containing the R16 and R17 nNos binding protein domains. Preclinical data in mouse models of DMD demonstrated rapid transduction, robust microdystrophin expression levels in the heart, quadriceps, and diaphragm by day 4 post-gene therapy treatment. In nonhuman primates, SGT-003 showed promising data, including increased biodistribution to cardiac and skeletal muscle, including the diaphragm, compared with first generation microdystrophin AAV9 gene therapies, suggesting increased transgene expression and an improved safety profile.

Solid Biosciences receives FDA clearance for SGT-003, an investigational gene therapy for treating Duchenne muscular dystrophy.
SGT-003 combines the microdystrophin transgene with a next-generation capsid, and unique manufacturing to address unmet needs.
The phase 1/2 trial, SGT-003-101, aims to assess safety and tolerability, with a 1E14 vg/kg dose in pediatric DMD patients.

“IND clearance for SGT-003 is a critical step in bringing a potential next generation gene therapy to the clinic and making a meaningful impact on the lives of those living with Duchenne. We are working closely with clinical sites to dose the first participants, driven by the belief that better therapies are urgently required to treat this devastating disease,” Gabriel Brooks, MD, chief medical officer, Solid Bio, added.¹

A month prior to the IND clearance, in October 2023, Solid announced that it was deprioritizing its earlier-generation lead candidate gene therapy SGT-001, which was also being developed for the treatment of DMD, in favor of advancing SGT-003.²

“The Solid team has done incredible work in advancing Duchenne gene therapy, and its commitment to the Duchenne community aligns with AavantiBio’s patient-centric mission of bringing new therapies that can positively improve the quality of life of rare disease patients and their families. I also look forward to advancing our library of next generation cardiac and skeletal muscle capsids to extend our opportunities to bring treatment options to more people in need,” Cumbo said in an earlier statement.²