Taysha Gene Therapies, Inc. announced that the first pediatric patient has been dosed with TSHA-102 in the REVEAL Phase 1/2 pediatric trial in the United States (U.S.) evaluating the safety and preliminary efficacy of TSHA-102 in stage three female patients 5-8 years of age with Rett syndrome. The company also announced the United Kingdom (U.K.) Medicines and Healthcare products Regulatory Agency (MHRA) has authorized the Clinical Trial Application (CTA) for TSHA-102 in pediatric patients, enabling expansion of the ongoing U.S. REVEAL pediatric trial into the U.K. TSHA-102 is a self-complementary intrathecally delivered AAV9 investigational gene transfer therapy that utilizes a 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. Initial dosing in the REVEAL Phase1/2 pediatric trial took place at RUSH University Medical Center in Chicago under Principal Investigator Elizabeth Berry-Kravis, M.D., Ph.D., Professor of Pediatrics, Neurology and Anatomy/Cell Biology at RUSH University Medical Center.

The REVEAL Phase 1/2 pediatric trial is an open-label, randomized, dose-escalation and dose-expansion study evaluating the safety and preliminary efficacy of TSHA-102 in pediatric females with Rett syndrome due to MECP2 loss-of-function mutation in the U.S. and U.K. TSHA-102 is administered as a single lumbar intrathecal injection. Part A of the study will focus on determining Maximum Administered Dose (MAD) and Maximum Tolerated Dose (MTD) in at least six patients (three per dose) aged 5-8 years old. Part B will evaluate TSHA-102 at the MAD or MTD in two age cohorts (5-8 years and 3-5 years).

The Company expects to complete dosing in cohort one (low dose) of the pediatric trial and report initial safety and efficacy data in mid-2024. TSHA-102 is also being evaluated in the ongoing first-in-human REVEAL Phase 1/2 adolescent and adult trial in females aged 12 and older with Rett syndrome in Canada. The Company previously reported initial clinical data from the first two adult patients dosed with TSHA-102.

Further updates on available clinical data from the low dose cohort in the REVEAL adolescent and adult trial are expected in the first quarter of 2024. TSHA-102 has received Fast Track designation and Orphan Drug and Rare Pediatric Disease designations from the FDA and has been granted Orphan Drug designation from the European Commission.