Taysha’s AAV Gene Therapy TSHA-102 Granted FDA Breakthrough Designation for Rett Syndrome

DALLAS, Texas – October 02, 2025 – Taysha Gene Therapies, Inc., a clinical-stage biotechnology company specializing in adeno-associated virus (AAV)-based gene therapies for the central nervous system (CNS), today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to TSHA-102.

TSHA-102 is an intrathecally delivered AAV9 gene therapy designed with disease-modifying potential for the treatment of Rett syndrome. The company also confirmed it has finalized the pivotal trial protocol and Statistical Analysis Plan (SAP) for the REVEAL trial, clearing the way for a planned Biologics License Application (BLA) submission.

Breakthrough Status Driven by Unprecedented Clinical Response
The FDA’s decision to grant Breakthrough Therapy designation—which expedites development and review—was based on the agency’s review of positive clinical data from Part A of the Phase 1/2 REVEAL trials.

Clinical evidence supporting the designation included data from 12 treated patients, demonstrating a 100% response rate (as of May 2025 data cutoff) for the primary endpoint: the gain or regain of ≥1 defined developmental milestone. Based on natural history data, the likelihood of this occurring without treatment is less than 6.7%. These findings, along with dose-dependent improvements in measures like the Revised Motor Behavior Assessment (R-MBA), underscored the substantial potential of the AAV therapy.

“Breakthrough Therapy designation highlights the FDA’s recognition of both the significant unmet medical need… and the potential of TSHA-102 to redefine the treatment paradigm for this devastating disease,” said Rumana Haque-Ahmed, Chief Regulatory Officer of Taysha.

Pivotal Trial Protocol Finalized, BLA Submission Expedited
Following the resolution of all remaining clinical and statistical queries with the FDA, Taysha has finalized the protocol for the REVEAL pivotal trial. A key element of this final alignment is the inclusion of a 6-month interim analysis, which could serve as the basis for the BLA submission. This is expected to expedite the BLA submission for the AAV therapy by at least two full quarters.

Key elements of the REVEAL pivotal trial:

Design: Single-arm, open-label trial with each patient serving as their own control.

Treatment: A single intrathecal administration of a high dose of the AAV9 gene therapy TSHA-102 (1×1e15 total vector genomes [vg]).

Patients: 15 females aged 6 to less than 22 years in the developmental plateau population.

Primary Endpoint: Assessing the response rate, defined as the percentage of patients who gain or regain one or more of 28 defined developmental milestones, which have a ≤6.7% likelihood of spontaneous gain/regain in this patient population.

TSHA-102: An AAV Therapy Targeting the Genetic Root Cause
TSHA-102 is a self-complementary, intrathecally delivered AAV9 investigational gene transfer therapy. The one-time AAV treatment is designed to address the genetic root cause of Rett syndrome by delivering a functional copy of the MECP2 gene to CNS cells.

This particular AAV gene therapy uses a novel miRNA-Responsive Auto-Regulatory Element (miRARE) technology. This innovative element is engineered to mediate the levels of the MECP2 protein in the CNS on a cell-by-cell basis, mitigating the risk of protein overexpression which can be toxic.

TSHA-102 has already received multiple expedited designations, including Breakthrough Therapy, RMAT, Fast Track, and Orphan Drug designation from the FDA, underscoring the critical need for an AAV-based disease-modifying therapy.