Taysha Gene Therapies has achieved significant regulatory progress for its lead gene therapy candidate TSHA-102 in Rett syndrome, following productive interactions with the U.S. Food and Drug Administration (FDA). The company announced that it has obtained written alignment from the FDA on key elements of the pivotal Part B trial design and next steps for enabling study initiation.
In a notable regulatory development, the FDA has advised Taysha to submit the pivotal Part B trial protocol and associated statistical analysis plan as an amendment to the existing Investigational New Drug (IND) application. This approach eliminates the need for a formal end-of-phase meeting, potentially accelerating the path to study initiation and registration. The company expects to submit this IND amendment in the second quarter of 2025.
"We are pleased with the significant regulatory and clinical progress across our TSHA-102 program in clinical evaluation for children, adolescents and adults suffering from Rett syndrome. We believe our interactions with the U.S. FDA under the RMAT mechanism have consistently been productive and continue to support a clear path to registration," said Sean P. Nolan, Chairman and Chief Executive Officer of Taysha.
Clinical Safety Update
The company also provided a safety update on its ongoing REVEAL Phase 1/2 trials. As of the April 10, 2025 data cutoff, both the high dose (1x10^15 total vector genomes) and low dose (5.7x10^14 total vector genomes) of TSHA-102 continue to be generally well tolerated. No treatment-related serious adverse events (SAEs) or dose-limiting toxicities (DLTs) have been observed in the 10 pediatric, adolescent, and adult patients treated across both REVEAL trials. This includes six patients in the high dose cohort and four patients in the low dose cohort.
Nolan added, "We believe the progress we've made with the FDA on our registrational pathway supports the strength of our data-driven approach and further enables our goal to bring TSHA-102 to patients with this devastating disease as expeditiously as possible."
Upcoming Data Presentations
Taysha will have a significant presence at the upcoming 2025 International Rett Syndrome Foundation (IRSF) Rett Syndrome Scientific Meeting taking place in Boston from June 9-11, 2025. The company will host three oral presentations related to TSHA-102 at this meeting.
In conjunction with this scientific meeting, Taysha plans to provide comprehensive updates on:
- Pivotal trial design for TSHA-102
- Rett syndrome natural history data analysis
- Safety and efficacy data for cohort two (high dose; n=6) and cohort one (low dose; n=4) from both the REVEAL Phase 1/2 adolescent and adult trial and the REVEAL Phase 1/2 pediatric trial
About TSHA-102 and Rett Syndrome
TSHA-102 is a self-complementary intrathecally delivered AAV9 investigational gene transfer therapy designed as a one-time treatment for Rett syndrome. The therapy aims to address the genetic root cause of the disease by delivering a functional form of MECP2 to cells in the central nervous system (CNS).
What distinguishes TSHA-102 is its 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. This approach is critical given the sensitivity of MECP2 expression levels in the brain.
The therapy has received multiple regulatory designations, including Regenerative Medicine Advanced Therapy, Fast Track, and Orphan Drug and Rare Pediatric Disease designations from the FDA, Orphan Drug designation from the European Commission, and Innovative Licensing and Access Pathway designation from the UK's Medicines and Healthcare products Regulatory Agency.
Rett syndrome is a rare neurodevelopmental disorder primarily affecting females, caused by mutations in the X-linked MECP2 gene. The disorder progresses through four key stages, beginning with early onset stagnation at 6 to 18 months of age, followed by rapid regression, plateau, and late motor deterioration. Patients experience loss of communication and hand function, developmental regression, motor and respiratory impairment, seizures, and intellectual disabilities.
Currently, there are no approved disease-modifying therapies that treat the genetic root cause of Rett syndrome. The condition affects an estimated 15,000 to 20,000 patients in the U.S., EU, and UK.
Financial Position
As of March 31, 2025, Taysha reported $116.6 million in cash and cash equivalents. The company expects its current cash resources to support planned operating expenses and capital requirements into the fourth quarter of 2026, providing runway through key clinical and regulatory milestones.
For the first quarter of 2025, Taysha reported a net loss of $21.5 million, or $0.08 per share, compared to a net loss of $24.1 million, or $0.10 per share, for the first quarter of 2024. Research and development expenses were $15.6 million, down from $20.7 million in the same period last year, primarily due to the completion of Good Manufacturing Practices batch activities for TSHA-102 in the prior year period.
The advancement of TSHA-102 represents a significant opportunity to address the unmet medical need in Rett syndrome with a potentially transformative gene therapy approach. The company's progress with regulatory authorities and ongoing clinical trials positions it to potentially deliver a first-in-class treatment for this devastating condition.
