Taysha Gene Therapies Inc 2025年度报告

2025 ANNUAL REPORT Letter FromThe CEO Dear Stockholders, 2025 was a year of significant execution for Taysha as we advanced our gene therapycandidate, TSHA-102, for the treatment of Rett syndrome. Throughout the past year,we generated compelling data across Part A of our REVEAL Phase 1/2 trials and madeimportant regulatory progress in defining a streamlined path to a Biologics LicenseApplication (BLA) submission to support a potential broad label for TSHA-102 inindividuals aged two years and older with Rett syndrome. We achieved several important milestones, including Breakthrough Therapy designationfor TSHA-102 from the United States (U.S.) Food and Drug Administration (FDA),initiation of our REVEAL pivotal trial, FDA clearance to initiate our safety-focused ASPIREtrial, and FDA alignment on chemistry, manufacturing, and controls (CMC) requirements,which collectively will support our planned BLA submission for TSHA-102. In parallel, westrengthened our balance sheet and extended our cash runway into 2028, supportingcontinued investment across clinical, regulatory and commercial activities. This progresshas set the stage for what we believe will be a transformative year ahead as we focuson completing the pivotal development of TSHA-102 and bolstering our commercialreadiness efforts as we advance toward potential registration. Rett syndrome is a devastating, rare and progressive neurodevelopmental diseasewith a high unmet need and a profound, lifelong burden for patients and caregivers.It is well-characterized clinically, defined by impairments across multiple clinicaldomains, including fine and gross motor function, communication, autonomic functionand seizures. Our work is driven by the high unmet needs of those impacted by Rettsyndrome. There are currently no approved disease-modifying therapies that treat thegenetic root cause of Rett syndrome, which affects an estimated 15,000 to 20,000patients in the U.S., Europe and the United Kingdom. TSHA 102 is a one-time, intrathecally delivered gene therapy uniquely designed toaddress the genetic root cause of Rett syndrome, with the potential to meaningfully alter the natural history of the disease and offer patients the opportunity to achieve functionalmilestones that would be otherwise impossible, according to natural history data. Basedon the clinical data we’ve reported to date, we believe TSHA-102 may deliver meaningfuland durable functional improvements across a broad population of patients, includingpediatrics, adolescents and adults with varying genotypes and severity of disease. Compelling REVEAL Phase 1/2 Clinical Data Across Broad Patient Population Part A of our REVEAL Phase 1/2 trials is evaluating the safety and preliminary efficacyof TSHA-102 at two dose levels, 5.7×10¹⁴ vector genomes (vg) (low dose) and 1×10¹⁵ vg(high dose), to determine the dose for the pivotal trial. A total of 12 participants, aged6 to 21 years, were treated with TSHA-102 in Part A of the studies. Both doses havedemonstrated an encouraging safety profile, and TSHA-102 has been generally well-tolerated with no treatment-related serious adverse events or dose-limiting toxicities asof the March 2026 data cutoff. In 2025, we presented compelling data from Part A of the trials across pediatric,adolescent and adult patients at the 2025 International Rett Syndrome Foundation(IRSF) Rett Syndrome Scientific Meeting. The data demonstrated that 100% of patientsgained one or more defined developmental milestone across the core functional domainsof fine motor, gross motor and communication post-treatment, with a consistentpattern of early sustained gains and new achievements continuing to emerge over time.In addition to the developmental milestones achieved across the treatment cohort,patients consistently gained multiple additional skills and improvements in core diseasecharacteristics as well as improvements across multiple clinician-assessed outcomemeasures, including the Revised Motor Behavior Assessment (R-MBA) and ClinicianGlobal Impression – Improvement (CGI-I). The high dose of TSHA-102 consistentlyoutperformed the low dose, with dose-dependent effects deepening over time. Based on Taysha’s robust analysis of the National Institutes of Health-funded IRSFnatural history study data, patients six years and older with Rett syndrome have a 0%to less than 6.7% likelihood of spontaneously gaining new or regaining developmentalmilestones that were lost after a defined number of years. We believe the unprecedentedfunctional gains consistently seen post-TSHA-102 reinforce its potentially broadtherapeutic impact on activities of daily living that are most important to caregivers andclinicians. Following FDA review of these data, we were pleased to receive Breakthrough Therapydesignation for TSHA-102, which we believe highlights the FDA’s recognition of both thesignificant unmet medical need and the therapeutic potential of TSHA-102 to redefinethe treatment paradigm for this devast