Solid Biosciences Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for SGT-212 for the treatment of Friedreich’s ataxia (FA), a degenerative disease caused by insufficient levels of the frataxin protein. SGT-212 is the Company’s novel, AAV-based FA gene therapy candidate designed to deliver full-length frataxin via systemic intravenous (IV) infusion as well as direct intradentate nuclei (IDN) infusion into the cerebellum. SGT-212 is designed to treat the neurologic and systemic clinical manifestations of FA to address the full spectrum of disease progression.
FA is a highly complex, multisystem disease that presents distinct challenges for drug development, in part because frataxin is a protein that requires: (1) precise expression levels to avoid fatal cardiac toxicities, and (2) on-target tissue localization in the cerebellum to achieve potential neurological clinical benefit. SGT-212 is the only candidate in development using two routes of administration to address the cardiac manifestations of FA while also directly delivering therapy to the dentate nuclei in the cerebellum, the region most affected and implicated in FA-associated neurologic decline.
Bo Cumbo, President and CEO of Solid Biosciences, commented: “SGT-212 has been intentionally designed to enable highly targeted delivery of our gene therapy to both the dentate nuclei and cardiac tissue. The IND was supported by a robust preclinical package demonstrating safe transduction and frataxin expression in these target tissues, with significant restoration of neurologic function and reversal of the cardiac implications of the disorder in mice. Over the years, we have tested several candidates using different methods of administration and have conducted multiple NHP studies, some of which extended out to a year. Based on this research, we believe a dual route of administration targeting multiple systems is the best approach in development to directly address the neurological implications that profoundly impact the everyday life of patients, while simultaneously targeting the cardiac manifestations that play a key role in more progressed disease. SGT-212 offers a truly differentiated approach to addressing FA with the potential to treat the full spectrum of symptoms, and we hope to meet each patient where they are in their FA disease course.”
Jennifer Farmer, Chief Executive Officer of the Friedreich’s Ataxia Research Alliance (FARA), added: “We congratulate Solid Biosciences on reaching this significant milestone. Gene therapy approaches are aimed at the underlying causes of FA, and thus important in the overall strategy to treat and cure this disease. There has been encouraging progress in the FA treatment landscape; however, there is still unmet medical need for our patient community. Through our work with individuals living with FA and their families, we know they seek therapies designed to treat the debilitating neurologic symptoms that people living with FA face day-to-day, such as loss of ambulation and coordination, dysarthria, along with the life-shortening cardiac disease. SGT-212’s unique, precision approach targets both the cerebellum and cardiac tissue using a dual route of administration, and in doing so, aims to address the underlying cause of the disease and the progression of FA. We look forward to continued partnership with the Company as they advance SGT-212 into the clinic later this year.”
In the second half of 2025, the Company expects to initiate a first-in-human, open-label, dose-finding Phase 1b clinical trial of SGT-212. The study will enroll non-ambulatory and ambulatory adult patients living with FA across up to three cohorts and will evaluate the safety and tolerability of contemporaneous systemic and bilateral IDN administration of SGT-212. Participants in the trial will be followed out to five years after receiving SGT-212.
Mr. Cumbo continued: “We are thankful for our strong partnerships with FARA, the FA patient community, FA212 LLC led by Tom Hamilton, the University of Pennsylvania and James Wilson M.D. Ph.D., all of whom contributed to research and development leading to this IND clearance. We would also like to recognize the University of Florida for its commitment to FA and the tireless work conducted on our behalf in support of patients.”