Solid Biosciences Announces FDA IND Clearance for First-In-Industry Dual Route of Administration Gene Therapy to Treat Both Neurologic and Cardiac Manifestations of Friedreich鈥檚 Ataxia
Solid Biosciences (NASDAQ: SLDB) has received FDA IND clearance for SGT-212, a pioneering dual-route gene therapy designed to treat Friedreich's ataxia (FA). This therapy is unique as it's the only candidate delivering full-length frataxin protein through both systemic intravenous infusion and direct intradentate nuclei infusion into the cerebellum.
The therapy aims to address both neurologic and cardiac manifestations of FA, targeting the insufficient levels of frataxin protein that cause this degenerative disease. Preclinical studies have shown safe transduction and frataxin expression in target tissues, demonstrating significant restoration of neurologic function and reversal of cardiac implications in mice.
The company plans to initiate a Phase 1b clinical trial in the second half of 2025. This first-in-human, open-label, dose-finding study will enroll both non-ambulatory and ambulatory adult FA patients across up to three cohorts, with participants being followed for five years after receiving SGT-212.
Solid Biosciences (NASDAQ: SLDB) ha ricevuto l'autorizzazione IND dalla FDA per SGT-212, una terapia genica innovativa a doppia via progettata per trattare l'Atassia di Friedreich (FA). Questa terapia 猫 unica poich茅 猫 l'unico candidato in grado di somministrare la proteina frataxina a lunghezza completa sia tramite infusione sistemica endovenosa che mediante infusione diretta nei nuclei intradentati nel cervelletto.
Il trattamento mira a affrontare sia le manifestazioni neurologiche che quelle cardiache della FA, mirando ai livelli insufficienti di proteina frataxina che causano questa malattia degenerativa. Gli studi preclinici hanno dimostrato una trasduzione sicura e un'espressione di frataxina nei tessuti target, mostrando un significativo ripristino della funzione neurologica e una reversibilit脿 delle implicazioni cardiache nei topi.
L'azienda prevede di avviare un studio clinico di Fase 1b nella seconda met脿 del 2025. Questo studio di prima applicazione sull'uomo, a etichetta aperta e di ricerca della dose, arruoler脿 sia pazienti adulti FA non deambulatori che deambulatori su un massimo di tre coorti, con i partecipanti seguiti per cinque anni dopo aver ricevuto SGT-212.
Solid Biosciences (NASDAQ: SLDB) ha recibido la autorizaci贸n IND de la FDA para SGT-212, una terapia g茅nica pionera de doble v铆a dise帽ada para tratar la ataxia de Friedreich (FA). Esta terapia es 煤nica, ya que es el 煤nico candidato que entrega la prote铆na frataxina en su forma completa a trav茅s de infusi贸n intravenosa sist茅mica y mediante infusi贸n directa en los n煤cleos intradentados del cerebelo.
El objetivo de la terapia es abordar tanto las manifestaciones neurol贸gicas como card铆acas de la FA, enfoc谩ndose en los niveles insuficientes de prote铆na frataxina que ocasionan esta enfermedad degenerativa. Los estudios precl铆nicos han demostrado una transducci贸n segura y expresi贸n de frataxina en los tejidos objetivo, mostrando una restauraci贸n significativa de la funci贸n neurol贸gica y reversi贸n de las implicaciones card铆acas en ratones.
La empresa planea iniciar un ensayo cl铆nico de Fase 1b en la segunda mitad de 2025. Este estudio de primera administraci贸n en humanos, de etiqueta abierta y de b煤squeda de dosis, incluir谩 tanto a pacientes adultos FA no ambulatorios como ambulatorios en hasta tres cohortes, con seguimiento a los participantes durante cinco a帽os despu茅s de recibir SGT-212.
靻旊Μ霌 氚旍澊鞓れ偓鞚挫柛鞀 (NASDAQ: SLDB)電 頂勲Μ霌滊Μ頌 鞁れ“歃(FA) 旃橂毳 鞙勴暣 靹り硠霅 順侅嫚鞝侅澑 鞚挫 瓴诫 鞙犾爠鞛 鞖旊矔 SGT-212鞐 雽頃 FDA IND 鞀轨澑鞚 氚涭晿鞀惦媹雼. 鞚 旃橂氩曥潃 鞝曤Д 欤检瀰瓿 靻岆噷鞚 旃橃晞頃奠棎 歆侅爲 欤检瀰鞚 韱淀暣 鞝勳泊 旮胳澊鞚 頂勲澕韮侅嫚 雼氨歆堨潉 鞝勲嫭頃橂姅 鞙犾澕頃 頉勲炒鞚搓赴 霑岆鞐 霃呿姽頃╇媹雼.
鞚 旃橂氩曥潃 FA鞚 鞁犼步 氚 鞁槇甏 歃濎儊鞚 氇憪 頃搓舶頃橂姅 瓴冹潉 氇╉憸搿 頃橂┌, 鞚 韲错枆靹 歆堩櫂鞚 鞙犽皽頃橂姅 頂勲澕韮侅嫚 雼氨歆堨潣 攵臁表暅 靾橃鞚 瓴儱頃╇媹雼. 鞝勳瀯靸 鞐瓣惮鞐愳劀電 氇╉憸 臁办鞐愳劀鞚 鞎堨爠頃 鞝勳澊鞕 頂勲澕韮侅嫚 氚滍槃鞚 氤挫棳欤检棃鞙茧┌, 欹愳棎靹 鞁犼步 旮半姤鞚 鞙犾潣氙疙暅 須岆车瓿 鞁灔鞝來暕靹膘潣 鞐爠鞚 雮橅儉雮姷雼堧嫟.
须岇偓电 2025雲 頃橂皹旮办棎 1b靸 鞛勳儊 鞁滍棙鞚 鞁滌瀾頃 瓿勴殟鞛呺媹雼. 鞚 觳 氩堨Ц 靷瀸鞐 雽頃 鞐瓣惮搿, 瓿店皽 霛茧波鞚 臧歆 鞖╇焿 韮愳儔 鞐瓣惮搿, 斓滊寑 靹 臧滌潣 歆戨嫧鞐愳劀 牍勲炒頄 靹膘澑 FA 頇橃瀽鞕 氤错枆 靹膘澑 FA 頇橃瀽毳 氇頃橂┌, SGT-212毳 氚涭潃 頉 5雲 霃欖晥 彀戈皜鞛愲ゼ 於旍爜頃 鞓堨爼鞛呺媹雼.
Solid Biosciences (NASDAQ: SLDB) a re莽u l'autorisation IND de la FDA pour SGT-212, une th茅rapie g茅nique innovante 脿 double voie con莽ue pour traiter l'ataxie de Friedreich (FA). Cette th茅rapie est unique, car elle est le seul candidat 脿 administrer la prot茅ine frataxine en pleine longueur 脿 la fois par infusion intraveineuse syst茅mique et par infusion directe dans les noyaux intradent茅s du cervelet.
La th茅rapie vise 脿 traiter 脿 la fois les manifestations neurologiques et cardiaques de la FA, en ciblant les niveaux insuffisants de la prot茅ine frataxine qui causent cette maladie d茅g茅n茅rative. Des 茅tudes pr茅cliniques ont montr茅 une transduction s没re et une expression de frataxine dans les tissus cibles, d茅montrant une restauration significative de la fonction neurologique et une inversion des implications cardiaques chez les souris.
L'entreprise pr茅voit de lancer un essai clinique de phase 1b dans la deuxi猫me moiti茅 de 2025. Cette 茅tude de premi猫re intention chez l'homme, ouverte et de recherche de dose, recrutera 脿 la fois des patients adultes FA non marchands et marchands au sein de trois cohortes, avec un suivi des participants pendant cinq ans apr猫s avoir re莽u SGT-212.
Solid Biosciences (NASDAQ: SLDB) hat von der FDA die IND-Zulassung f眉r SGT-212 erhalten, eine bahnbrechende duale Gen-Therapie, die zur Behandlung der Friedreich-Ataxie (FA) entwickelt wurde. Diese Therapie ist einzigartig, da sie als einzige Kandidatin das vollst盲ndige Frataxin-Protein sowohl durch systemische intraven枚se Infusion als auch durch direkte Injektion in die intradentaten Kerne des Kleinhirns bereitstellt.
Das Ziel der Therapie ist es, sowohl die neurologischen als auch die kardialen Manifestationen der FA zu bek盲mpfen, indem die unzureichenden Frataxin-Proteinspiegel, die diese degenerative Erkrankung verursachen, angegangen werden. In vorklinischen Studien wurde eine sichere Transduktion und Frataxin-Expression in den Zielgeweben gezeigt, was zu einer signifikanten Wiederherstellung der neurologischen Funktion und zur Umkehr der kardiologischen Auswirkungen bei M盲usen f眉hrte.
Das Unternehmen plant, im zweiten Halbjahr 2025 eine klinische Phase-1b-Studie zu beginnen. Diese erste Studie am Menschen, die offen und dosisfindend ist, wird sowohl nicht gehf盲hige als auch gehf盲hige erwachsene FA-Patienten in bis zu drei Gruppen einschlie脽en, wobei die Teilnehmer f眉nf Jahre nach Erhalt von SGT-212 verfolgt werden.
- First FDA IND clearance for dual-route gene therapy targeting both neurologic and cardiac FA symptoms
- Successful preclinical results showing restoration of neurologic function and cardiac improvement in mice
- Unique market position as the only candidate using dual administration approach
- Phase 1b clinical trial not starting until second half of 2025
- Long five-year follow-up period required for trial participants
- Complex delivery method requiring both systemic and direct brain infusion
Insights
The FDA IND clearance for SGT-212 represents a pivotal milestone in Friedreich's ataxia (FA) treatment. The dual delivery approach - intravenous and intradentate nuclei infusion - is a groundbreaking innovation targeting both cardiac and neurological manifestations simultaneously. This strategic approach addresses two critical challenges: precise frataxin protein expression to prevent cardiac toxicity and targeted cerebellar delivery for neurological benefit.
The preclinical data package demonstrates compelling efficacy, showing restoration of neurologic function and reversal of cardiac symptoms in mouse models. The planned Phase 1b trial structure, incorporating both ambulatory and non-ambulatory patients across multiple cohorts with a 5-year follow-up period, is well-designed to evaluate long-term safety and efficacy. The collaboration with prominent institutions and researchers, including UPenn and Dr. James Wilson, adds significant credibility to the program.
For a
The therapeutic strategy of SGT-212 is particularly noteworthy from a clinical perspective. Friedreich's ataxia's complex pathology requires addressing both cerebellar degeneration and cardiac complications. The direct IDN infusion into the cerebellum is crucial, as this region is central to motor coordination and balance - primary symptoms that severely impact FA patients' quality of life.
The inclusion of both ambulatory and non-ambulatory patients in the upcoming trial is strategically important, as it will help define the therapy's potential across different disease stages. This could potentially expand the addressable patient population and provide valuable insights into optimal treatment timing. The 5-year follow-up period is essential for assessing long-term safety and durability of effect, particularly important for gene therapy approaches.
From a gene therapy development standpoint, SGT-212's approach tackles several critical technical challenges. The AAV-based delivery system combined with dual-route administration represents sophisticated engineering to achieve targeted tissue distribution. The ability to maintain precise frataxin expression levels is crucial, as both under and over-expression can be problematic.
The extensive preclinical work, including year-long non-human primate studies, provides robust safety data supporting the IND clearance. This comprehensive development approach, particularly the focus on controlled protein expression and specific tissue targeting, sets a new standard for gene therapy development in complex multisystem disorders. The timing for Phase 1b initiation in 2H 2025 allows for proper preparation of clinical sites and manufacturing scale-up.
- SGT-212 is the only full-length frataxin replacement gene therapy candidate targeting the CNS and cardiac manifestations of Friedreich鈥檚 ataxia -
- Dual route of administration enables direct delivery of AAV-based gene therapy to the cerebellum and heart to potentially address the most significant symptoms of the disease -
- Phase 1b clinical trial initiation expected in 2H 2025 -
- Company to hold a conference call tomorrow, January 8, 2025, at 8:30 AM ET -
CHARLESTOWN, Mass., Jan. 07, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB) (the 鈥淐ompany鈥 or 鈥淪olid鈥), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today 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鈥檚 ataxia (FA), a degenerative disease caused by insufficient levels of the frataxin protein. SGT-212 is the Company鈥檚 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: 鈥淪GT-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.鈥
Jennifer Farmer, Chief Executive Officer of the Friedreich鈥檚 Ataxia Research Alliance (FARA), added: 鈥淲e 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.鈥
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: 鈥淲e 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.鈥
Conference Call
The Company will host a conference call tomorrow, January 8, 2025, at 8:30 AM ET to discuss the IND clearance for SGT-212 as well as other corporate updates. A live and archived webcast of the call will be available on Solid鈥檚 website at under the 鈥淣ews & Events鈥 tab in the Investor Relations section, or by clicking here.
Participants may also access the live call by dialing 877-409-2291 (toll-free) or 201-389-0925 (international).
About SGT-212
SGT-212 is a recombinant AAV-based gene replacement therapy for Friedreich鈥檚 ataxia (FA) designed to deliver full-length human frataxin (Fxn) via a dual route of administration: intradentate nucleus (IDN) infusion, using an MRI-guided device, followed by an intravenous (IV) infusion to increase therapeutic Fxn levels in the cerebellar dentate nuclei and in the cardiomyocytes, respectively. Restoration of Fxn levels is expected to repair the underlying mitochondrial dysfunction in neurons and cardiomyocytes to address both neurologic and cardiac manifestations of the disease.
SGT-212 was developed by FA212 LLC, a company founded by parents of children living with FA, the University of Pennsylvania, and Solid Biosciences.
University of Pennsylvania Financial Disclosure: The laboratory of Dr. Wilson at the University of Pennsylvania received sponsored research funding from FA212 LLC. Penn owns an equity interest in FA212 LLC. Penn and Dr. Wilson have either received, or may receive in the future, financial consideration related to the licensing of certain Penn intellectual property to Solid Biosciences.
About Friedreich鈥檚 Ataxia (FA)
FA is an inherited, life-threatening, degenerative multisystem disease caused by defects in the frataxin gene that disrupt production of the frataxin protein, a mitochondrial iron-binding protein involved in essential cellular processes, including energy production. FA is known to cause progressive nervous system damage, movement problems, and cardiac dysfunction, with cardiac complications identified as the primary cause of death. FA impacts approximately 5,000 people in the United States and 15,000 in Europe. There are currently no treatments that provide a cure or halt disease progression.
About FARA
The Friedreich鈥檚 Ataxia Research Alliance (FARA) is a national nonprofit organization dedicated to curing Friedreich鈥檚 ataxia (FA) through research. FARA grants and activities provide support for basic and translational FA research, pharmaceutical/biotech drug development, clinical trials, and scientific conferences. FARA also serves as a catalyst, between the public and scientific community, to create worldwide exchanges of information that drive medical advances. For more information about FARA, visit聽.
About Solid Biosciences
Solid Biosciences is a precision genetic medicine company focused on advancing a portfolio of gene therapy candidates including SGT-003 for the treatment of Duchenne muscular dystrophy (Duchenne), SGT-212 for the treatment of Friedreich鈥檚 ataxia, SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), SGT-601 for the treatment of TNNT2-mediated dilated cardiomyopathy, SGT-401 for the treatment of BAG3-mediated dilated cardiomyopathy, and additional assets for the treatment of fatal cardiac diseases. Solid is advancing its diverse pipeline across rare neuromuscular and cardiac diseases, bringing together experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted, Solid鈥檚 mandate is to improve the daily lives of patients living with these devastating diseases. For more information, please visit .
Forward-Looking Statements
This press release contains 鈥渇orward-looking statements鈥 within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding future expectations, plans and prospects for the Company; the ability to successfully achieve and execute on the company鈥檚 goals, priorities and achieve key clinical milestones; the Company鈥檚 pipeline of programs for neuromuscular and cardiac diseases, including its SGT-212 and SGT-003 programs and expectations for CTA filings, site activations, clinical development, initiation and enrollment in clinical trials, dosing, availability of clinical trial data and potential accelerated approval; the sufficiency of the Company鈥檚 cash, cash equivalents, and available-for-sale securities to fund its operations; and other statements containing the words 鈥渁nticipate,鈥 鈥渂elieve,鈥 鈥渃ontinue,鈥 鈥渃ould,鈥 鈥渆stimate,鈥 鈥渆xpect,鈥 鈥渋ntend,鈥 鈥渕ay,鈥 鈥減lan,鈥 鈥減otential,鈥 鈥減redict,鈥 鈥減roject,鈥 鈥渟hould,鈥 鈥渢arget,鈥 鈥渨ould,鈥 鈥渨orking鈥 and similar expressions. Any forward-looking statements are based on management鈥檚 current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the company鈥檚 ability to advance SGT-212, SGT-003, SGT-501, SGT-601, SGT-401 and other preclinical programs and capsid libraries on the timelines expected or at all; obtain and maintain necessary approvals from the FDA and other regulatory authorities; replicate in clinical trials positive results found in preclinical studies and early-stage clinical trials of the company鈥檚 product candidates; obtain, maintain or protect intellectual property rights related to its product candidates; compete successfully with other companies that are seeking to develop Duchenne, Friedreich鈥檚 ataxia and other neuromuscular and cardiac treatments and gene therapies; manage expenses; and raise the substantial additional capital needed, on the timeline necessary, to continue development of SGT-212, SGT-003, SGT-501, SGT-601, SGT-401 and other candidates, achieve its other business objectives and continue as a going concern. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the company鈥檚 actual results to differ from those contained in the forward-looking statements, see the 鈥淩isk Factors鈥 section, as well as discussions of potential risks, uncertainties and other important factors, in the company鈥檚 most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the company鈥檚 views as of the date hereof and should not be relied upon as representing the company鈥檚 views as of any date subsequent to the date hereof. The company anticipates that subsequent events and developments will cause the company's views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so.
Solid Biosciences Investor Contact:
Nicole Anderson
Director, Investor Relations and Corporate Communications
Solid Biosciences Inc.
Media Contact:
Glenn Silver
FINN Partners
FAQ
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