Solid’s Pipeline consists of three different capsid gene therapy programs designed to advance our rationally designed microdystrophin construct, uniquely inclusive of the neuronal nitric oxide synthase (nNOS) binding domain, to treat Duchenne Muscular Dystrophy.
Mechanism In Duchenne: The absence or near-absence of the protein dystrophin leads to muscle membrane instability and disruption of the dystrophin glycoprotein complex (DGC). Microdystrophin is a synthetic version of the dystrophin gene that is believed to retain its key components and functionality. In preclinical models, therapeutic administration of microdystrophin by adeno-associated virus (AAV) has been shown to stabilize the DGC and restore muscle function.
Impact on Duchenne: The large size of the dystrophin gene has historically prevented direct replacement as a therapeutic strategy. Preclinical studies have shown that microdystrophin AAV-mediated gene transfer enables systemic delivery of the truncated gene and has the potential to slow or halt disease progression, regardless of the type of dystrophin gene mutation.
Solid’s SGT-001 is a novel adeno-associated viral (AAV) vector-mediated gene transfer therapy designed to address the underlying genetic cause of Duchenne. SGT-001 is a systemically administered candidate that delivers microdystrophin to the body. This microdystrophin encodes for a functional protein surrogate that is expressed in muscles and stabilizes essential associated proteins, including nNOS. Data from Solid’s clinical program suggests that SGT-001 has the potential to slow or stop the progression of Duchenne.
SGT-001 is based on pioneering research in dystrophin biology by Dr. Jeffrey Chamberlain of the University of Washington and Dr. Dongsheng Duan of the University of Missouri. SGT-001 has been granted Rare Pediatric Disease Designation, or RPDD, and Fast Track Designation in the United States and Orphan Drug Designations in both the United States and European Union.
The safety and efficacy of SGT-001 are currently being evaluated in IGNITE-DMD, a Phase I/II clinical trial. For more information on this clinical trial, please visit www.clinicaltrials.gov and look for the study ID number: NCT03368742.
Solid’s SGT-003 is a rationally designed next generation adeno-associated virus (AAV) gene transfer therapy leveraging a novel, internally developed capsid with improved muscle-tropic properties. In preclinical studies, SGT-003 shows enhanced muscle tropism and microdystrophin expression. Biodistribution data show increased vector genomes in muscle and heart as well as decreased vector genomes in liver with SGT-003 compared to AAV9 in various in vitro and in vivo models. This biodistribution profile has the potential to increase efficiency and specifically target muscle cells, which could potentially allow for a reduced total viral load.
Solid Biosciences’ collaboration with Ultragenyx is designed to advance a next generation Duchenne muscular dystrophy construct comprised of Solid’s proprietary nNOS-binding microdystrophin construct and Ultragenyx’s HeLa PCL manufacturing platform for use with AAV8 and variants thereof.