Taysha Doses First Patient in Pivotal Trial for Rett Syndrome Gene Therapy TSHA-102, Aligns With FDA on BLA Plans

Taysha Gene Therapies has announced its dosing of the first patient in the pivotal phase 3 portion (Part B) of the REVEAL clinical trial (NCT05606614), which is evaluating investigational adeno-associated virus vector-based gene therapy TSHA-102 for the treatment of Rett syndrome.¹

According to Taysha, the first patient’s dosing took place in the fourth quarter of 2025. Enrollment is ongoing, and the trial is expected to enroll 15 female patients, aged 6 to less than 22 years, in total. The multicenter study will treat patients with a single, intrathecal dose of the gene therapy at 1x10¹⁵ total vector genomes (vg).

Alongside the announcement, Taysha also stated that it has obtained written alignment from the FDA regarding certain plans for a potential biologics license application (BLA) for TSHA-102. Specifically, the alignment relates to the separate, planned clinical trial referred to as ASPIRE (NCT identifier pending). ASPIRE will evaluate TSHA-102 in 3 girls aged 2 to less than 4 years with the same single 1x10¹⁵ total vg dose, scaled for lower brain volume in the included age group, with a focus on safety. Taysha has aligned with the FDA on the use of at least 3 months of data from this trial to support a BLA submission for the gene therapy aimed at an indication including patients aged 2 years and older.

"Dosing the first patient in our REVEAL pivotal trial last quarter represents a significant milestone in the development of TSHA-102 for Rett syndrome, and enrollment is further advancing across multiple sites,” Sean P. Nolan, BS, the chairman and chief executive officer of Taysha, said in a statement.¹ “As we progress pivotal development, we continue to maintain consistent and productive dialogue with the FDA. Importantly, we recently reached written alignment with the FDA that our planned BLA submission will include at least 3 months of safety data from 3 patients aged 2 to under 4 years in the ASPIRE trial to support a broad label for patients aged 2 years and older with Rett syndrome. We believe this recent alignment on ASPIRE, together with the alignment on a 6-month interim analysis for our REVEAL pivotal trial, streamlines our path toward BLA submission for TSHA-102. We expect to complete dosing across our REVEAL and ASPIRE trials in the second quarter of 2026. With an estimated 15,000 to 20,000 patients affected by Rett syndrome across the United States, European Union, and United Kingdom and compelling REVEAL Part A clinical data, we see a significant opportunity to redefine the treatment paradigm for this devastating disease with high unmet need.”

Part A of REVEAL, which includes an adolescent and adult (NCT05606614) and pediatric (NCT06152237) phase 1/2 study for TSHA-102, is ongoing, with an estimated primary completion date of November 2, 2028 for the pediatric study. Taysha noted that it expects to announce new data from Part A before the end of the first half of 2026.

Notably, previously announced data from Part A of the adolescent and adult study with a data cut off in May 2025 showed that patients treated with TSHA-102 achieved a 100% response rate with regard to gain or regain of 1 or more defined developmental milestones, which constitutes the pivotal trial’s primary end point.² Taysha noted that based on natural history data, there is a less than 6.7% likelihood of such developmental milestones being gained or regained without treatment. The company characterized TSHA-102's safety profile as “well tolerated” in part A. Also of note, in October 2025, Taysha announced that TSHA-102 had received breakthrough therapy designation from the FDA.

“Breakthrough therapy designation highlights the FDA’s recognition of both the significant unmet medical need across the estimated 10,000 patients suffering from Rett syndrome in the United States and the potential of TSHA-102 to redefine the treatment paradigm for this devastating disease,” Rumana Haque-Ahmed, the chief regulatory officer of Taysha, said in an October 2025 statement.² “This designation was granted following the FDA’s review of available clinical data from the 12 patients treated in part A of our REVEAL trials, which support the potential of TSHA-102 to improve function and enable achievement of developmental milestones across core areas of disease that may significantly impact patient and caregiver lives. The disease burden in Rett syndrome continues to be significant, and we are encouraged by the potential of TSHA-102 to address its underlying cause. We look forward to continued collaboration with the FDA as we advance toward potential registration.”

REFERENCES
1. Taysha Gene Therapies announces progress across TSHA-102 pivotal gene therapy program in Rett syndrome. News release. Taysha Gene Therapies, Inc. January 6, 2026. Accessed January 30, 2026. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-progress-across-tsha-102-pivotal
2. Taysha Gene Therapies announces FDA breakthrough therapy designation and provides positive regulatory update on TSHA-102 in Rett syndrome. News release. Taysha Gene Therapies Inc. October 2, 2025. Accessed January 30, 2026. https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-fda-breakthrough-therapy