TSHA-102 / Taysha Gene Therapies - LARVOL DELTA

ASPIRE: Safety and Preliminary Efficacy of TSHA-102 Gene Therapy in Pediatric Females Aged >2 to <4 Years With Rett Syndrome (clinicaltrials.gov) - P3 | N=4 | Active, not recruiting | Sponsor: Taysha Gene Therapies, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Developmental Disorders • Gene Therapies • Movement Disorders • Pediatrics

A Phase 1/2/3 Study of TSHA-102 Gene Therapy in Females With Rett Syndrome (REVEAL Pivotal Study) (clinicaltrials.gov) - P3 | N=17 | Active, not recruiting | Sponsor: Taysha Gene Therapies, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Developmental Disorders • Gene Therapies • Movement Disorders

Taysha Gene Therapies, Inc. announced multiple presentations highlighting its TSHA-102 program for Rett syndrome at the 2026 International Rett Syndrome Foundation (IRSF) Rett Syndrome Scientific Meeting held in Prior Lake, MN, from June 29 to July 1, 2026. (Scanx) - "The presentations included safety and efficacy results from the REVEAL Part A Phase 1/2 trial in pediatric and adolescent/adult cohorts, delivered by Principal Investigator Elsa Rossignol, M.D. New data supported the Rett Syndrome Developmental Milestone Assessment (RS-DMA) as a psychometrically valid, FDA-supported primary endpoint for single-arm interventional studies. Preclinical findings demonstrated superior MeCP2 expression of self-complementary AAV9 compared to single-stranded vectors, supporting effective central nervous system delivery via intrathecal administration."

P1/2 data • Preclinical • CNS Disorders

ASPIRE: Safety and Preliminary Efficacy of TSHA-102 Gene Therapy in Pediatric Females Aged >2 to <4 Years With Rett Syndrome (clinicaltrials.gov) - P3 | N=3 | Recruiting | Sponsor: Taysha Gene Therapies, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Developmental Disorders • Gene Therapies • Movement Disorders • Pediatrics

Superior expression of self-complementary AAV and comparable functionality of mini and full-length MECP2 support the design of TSHA-102 gene therapy for Rett syndrome (ASGCT 2026) - "Conclusion These data demonstrate that self-complementary AAV9 enables markedly superior MeCP2 expression compared to single-stranded AAV9, and that mini-MeCP2 is a fully functional miniMeCP2 gene payload that retains the core molecular and biochemical functions of full-length MeCP2. Together, these results provide strong mechanistic support for the selection of scAAV9 and miniMeCP2 in the design of the TSHA-102 vector and the corresponding clinical outcomes observed in Taysha’s ongoing clinical studies."

Gene therapy • Developmental Disorders • Gene Therapies • Movement Disorders • DNMT3A

rAAV9 vector biodistribution in nonhuman primate brain and spinal cord following lumbar intrathecal infusion. (PubMed, Front Med (Lausanne)) - "A total of 48 animals were followed across five studies: four lumbar IT infusion studies with four recombinant adeno-associated virus serotype 9 vectors (TSHA-101, -102, -105, and -120); and one ICM infusion study (TSHA-102 only). At comparable doses and times, IT and ICM delivery led to widespread and consistent distribution of vector genomes, approximating 1 vg/diploid host genome throughout the brain at the higher doses tested. These findings support IT administration as an effective, minimally invasive approach to central nervous system-directed gene therapy."

Journal • CNS Disorders • Gene Therapies • Genetic Disorders

From Gene to Hope: Rett Syndrome and the Rise of Molecular Therapies. (PubMed, Mol Diagn Ther) - "We discuss clinical-stage adeno-associated virus gene replacement programs, including TSHA-102 and NGN-401, highlighting their vector designs, regulatory elements, delivery approaches, and emerging clinical data. Beyond gene supplementation, we explore approaches that restore endogenous MECP2 regulation, such as reactivation of the inactive X chromosome, as well as DNA and RNA editing strategies. Collectively, these advances reflect a shift toward precision-regulated therapies for Rett syndrome that may provide a model for treating other dosage-sensitive neurodevelopmental disorders."

Journal • Review • CNS Disorders • Developmental Disorders • Movement Disorders • Psychiatry

ASPIRE: Safety and Preliminary Efficacy of TSHA-102 Gene Therapy in Pediatric Females Aged >2 to <4 Years With Rett Syndrome (clinicaltrials.gov) - P3 | N=3 | Not yet recruiting | Sponsor: Taysha Gene Therapies, Inc.

New P3 trial • Developmental Disorders • Gene Therapies • Movement Disorders • Pediatrics

Disease-modifying therapies for Rett syndrome: a review for neurologists. (PubMed, Front Neurol) - "Until the recent approval of trofinetide, management relied exclusively on symptomatic treatment and multidisciplinary supportive care...TSHA-102 uses an intrathecally delivered miniMECP2 transgene regulated by a microRNA-based autoregulatory system, whereas NGN-401 delivers full-length MECP2 via intracerebroventricular administration using a synthetic expression-feedback circuit...Finally, we address key translational considerations such as optimal timing of intervention, dosing constraints, outcome measurement in severely impaired populations, long-term safety surveillance, and barriers to broad and equitable access. The RTT gene therapy experience serves as a model for precision medicine in other monogenic neurodevelopmental disorders, illustrating both the transformative promise and the substantial complexities of translating genetic science into meaningful clinical benefit."

Journal • Review • CNS Disorders • Developmental Disorders • Gene Therapies • Movement Disorders • Pediatrics • Psychiatry • ADAR

A Phase 1/2/3 Study of TSHA-102 Gene Therapy in Females With Rett Syndrome (REVEAL Pivotal Study) (clinicaltrials.gov) - P3 | N=15 | Recruiting | Sponsor: Taysha Gene Therapies, Inc. | Phase classification: P1/2 ➔ P3 | Trial completion date: Jan 2032 ➔ Jun 2031 | Trial primary completion date: Nov 2028 ➔ Jun 2031

Phase classification • Trial completion date • Trial primary completion date • Developmental Disorders • Gene Therapies • Movement Disorders

Broad CNS Biodistribution of AAV9-based Gene Therapies Delivered by Intrathecal Lumbar Puncture in Non-Human Primates (ESGCT 2024) - "During preclinical characterization of investigational gene therapies, biodistribution in NHPs of TSHA-101, TSHA-102, TSHA-105 and TSHA-120 was evaluated after administration by the IT (all products) or ICM (TSHA-102 only) routes. Overall, biodistribution analysis in Taysha’s NHP studies showed that both the IT and ICM routes led to comparable widespread AAV9 distribution throughout the CNS, achieving brain levels of ∼3 – 5 × 105 vg/µg at comparable doses and timing. These findings support the use of lumbar IT administration as an effective, procedurally simple approach for rAAV9 dosing of the CNS."

Gene therapy • Gene Therapies

Taysha Gene Therapies Regains Full Rights to Lead TSHA-102 Program in Clinical Evaluation for the Treatment of Rett Syndrome (GlobeNewswire) - "The 2022 Option Agreement between Astellas and Taysha, which had granted Astellas the exclusive option to enter a negotiation period to obtain an exclusive license to TSHA-102 in Rett syndrome and certain rights with respect to change in control transactions involving Taysha, has expired....Following the expiration of the Option Agreement, Taysha now holds unencumbered rights to the TSHA-102 program."

Commercial • CNS Disorders • Developmental Disorders

Taysha Gene Therapies Announces FDA Breakthrough Therapy Designation and Provides Positive Regulatory Update on TSHA-102 in Rett Syndrome (The Manila Times) - "Breakthrough Therapy designation granted based on FDA’s review of available clinical evidence of safety and efficacy from all 12 patients treated in Part A of the REVEAL Phase 1/2 trials...the Company announced that it has finalized alignment with the FDA on the REVEAL pivotal trial protocol and statistical analysis plan (SAP) that are intended to support the planned Biologics License Application (BLA) submission for TSHA-102, following the resolution of remaining clinical and statistical queries...'We remain on track to initiate patient enrollment for our REVEAL pivotal trial in the fourth quarter of 2025.'"

Breakthrough therapy • FDA event • New trial • CNS Disorders

Safety and Efficacy of TSHA-102 in Adolescent and Adult Females With Rett Syndrome (REVEAL Adult Study) (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Taysha Gene Therapies, Inc. | Trial primary completion date: Jan 2025 ➔ Nov 2028

Trial primary completion date • Developmental Disorders • Gene Therapies • Movement Disorders

Taysha Gene Therapies Announces Details for Oral Presentations at the 2025 IRSF Rett Syndrome Scientific Meeting Reviewing Recent Updates from the TSHA-102 Clinical Program - "Taysha Gene Therapies, Inc...announced details for three oral presentations reviewing recent updates supporting its TSHA-102 program in clinical evaluation for Rett syndrome, and a Taysha-hosted symposium on the Company’s analysis of the natural history study data at the 2025 International Rett Syndrome Foundation (IRSF) Rett Syndrome Scientific Meeting, taking place in Boston from June 9-11, 2025. The three presentations will also be presented during a poster session on Monday, June 9, 2025, from 5:00-7:00 PM EST."

Clinical data • Preclinical • CNS Disorders • Developmental Disorders

Taysha Gene Therapies Reports Full-Year 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Update on the pivotal trial design for TSHA-102 expected in the first half of 2025; REVEAL Adolescent and Adult Trial: Safety and efficacy data in cohort two (high dose; n=3) and an update on safety and efficacy data in cohort one (low dose; n=2) expected in the first half of 2025; REVEAL Pediatric Trial: Safety and efficacy data in cohort two (high dose; n=3) and an update on safety and efficacy data in cohort one (low dose; n=2) expected in the first half of 2025."

Clinical protocol • P1/2 data • CNS Disorders

Safety and Efficacy of TSHA-102 in Pediatric Females With Rett Syndrome (REVEAL Pediatric Study) (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: Taysha Gene Therapies, Inc. | Phase classification: P1 ➔ P1/2

Phase classification • Developmental Disorders • Gene Therapies • Movement Disorders • Pediatrics

Early safety and efficacy observations following the first use of TSHA‐102 gene therapy in a patient with Rett Syndrome (ESGCT 2023) - P1/2 | "They are generally well-controlled with clobazam and phenytoin, despite occasional breakthrough seizures during viral infections or when her blood phenytoin declines to <100 mmol/L. Ongoing medical challenges include persistent constipation, recurrent pneumonia, scoliosis, osteopenia, and a benign thyroid nodule identified in January 2023.Following sirolimus and prednisolone initiation at Day -7, TSHA-102 was injected intrathecally on Day 0...However, the participant started being able to sit unassisted for a few minutes by Day 35. Finally, whereas two seizures were recorded in the 10-day run-up to therapy, none occurred between Days 0 and +35, despite low blood phenytoin.Because Participant 1 experienced no dose-limiting toxicities, and considering the rapid clinical benefit she appears to be experiencing, the IDMC approved continuation of the REVEAL Adult study, with Participants 2 and 3 to receive the same dose of TSHA-102 as Participant 1, later in this..."

Clinical • Gene therapy • CNS Disorders • Constipation • Developmental Disorders • Epilepsy • Gastroenterology • Gastrointestinal Disorder • Gene Therapies • Hematological Disorders • Infectious Disease • Movement Disorders • Pneumonia • Respiratory Diseases

The microRNA‐responsive autoregulatory element from TSHA‐102 for Rett Syndrome modulates therapeutic transgene expression in response to cellular MeCP2 in mouse and human cell lines (ESGCT 2023) - "As hypothesized, miRARE-mediated modulation of miniMeCP2 expression appears to require cellular MeCP2 function. Further experiments are ongoing to characterize miRARE function and explore the relevance of cellular MeCP2 background for transgene expression in this system."

Preclinical • CNS Disorders • Developmental Disorders • Gene Therapies • Infectious Disease • Movement Disorders • Psychiatry

Taysha Gene Therapies Announces Regenerative Medicine Advanced Therapy (RMAT) Designation Granted by U.S. FDA for TSHA-102 in Rett Syndrome (GlobeNewswire) - "Taysha Gene Therapies, Inc...announced the United States Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to TSHA-102, a self-complementary intrathecally delivered AAV9 gene transfer therapy in clinical evaluation for Rett syndrome. RMAT designation was granted following the FDA’s review of clinical data supporting the potential of TSHA-102 to address the unmet medical need for patients with Rett syndrome....RMAT designation follows the FDA’s review of available safety and efficacy data from the first three patients with Rett syndrome dosed with the low dose of TSHA-102 (5.7x10¹⁴ total vg) across the REVEAL Phase 1/2 adolescent and adult trial and the REVEAL Phase 1/2 pediatric trial."

FDA event • CNS Disorders

The Efficacy of a Human-Ready miniMECP2 Gene Therapy in a Pre-Clinical Model of Rett Syndrome. (PubMed, Genes (Basel)) - P1/2 | "In female mice, TSHA-102 permitted survivals that were similar to those of vehicle-treated controls. In all, these pivotal data helped to support the regulatory approval to initiate a clinical trial for TSHA-102 in RTT patients (clinical trial identifier number NCT05606614)."

Gene therapy • Journal • Preclinical • Developmental Disorders • Gene Therapies • Movement Disorders

Safety and Efficacy of TSHA-102 in Pediatric Females With Rett Syndrome (REVEAL Pediatric Study) (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: Taysha Gene Therapies, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gene therapy • Developmental Disorders • Gene Therapies • Movement Disorders • Pediatrics

Safety and Efficacy of TSHA-102 in Pediatric Females With Rett Syndrome (REVEAL Pediatric Study) (clinicaltrials.gov) - P1 | N=6 | Not yet recruiting | Sponsor: Taysha Gene Therapies, Inc.

New P1 trial • Developmental Disorders • Gene Therapies • Movement Disorders • Pediatrics

Safety and Efficacy of TSHA-102 in Adult Females With Rett Syndrome (REVEAL Adult Study) (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Taysha Gene Therapies, Inc. | N=12 ➔ 18

Enrollment change • Developmental Disorders • Gene Therapies • Movement Disorders

Taysha Gene Therapies Announces Fast Track Designation Granted by U.S. FDA for TSHA-102 in Rett Syndrome (GlobeNewswire) - "Taysha Gene Therapies, Inc...today announced the U.S. FDA has granted Fast Track Designation (FTD) to TSHA-102, a self-complementary intrathecally delivered AAV9 gene transfer therapy in clinical evaluation for Rett syndrome. TSHA-102 utilizes the novel miRNA-Responsive Auto-Regulatory Element (miRARE) technology designed to mediate levels of MECP2 in the CNS on a cell-by-cell basis without risk of overexpression....The U.S. FDA cleared the IND application for TSHA-102 in pediatric patients with Rett syndrome, and the Company expects to dose the first pediatric patient in the first quarter of 2024."

Fast track designation • Trial status • CNS Disorders • Developmental Disorders