Taysha Gene Therapies Inc 2024年度报告

2024 ANNUAL REPORT Letter FromThe CEO Chairman and Chief Executive Officer Dear Stockholders, 2024 was an exciting year for Taysha, marked by progress in the advancement of our leadgene therapy candidate, TSHA-102, in clinical evaluation for pediatric, adolescent andadult patients with Rett syndrome. During the past year, we generated critical longer-term clinical data across a broad range of ages and stages of patients in our two ongoingREVEAL Phase 1/2 trials to further elucidate the therapeutic potential of TSHA-102 andinform the development plan for the pivotal phase of the trials. We achieved several key milestones, including the completion of dosing of the 10patients in the Part A dose escalation phase of the REVEAL Phase 1/2 adolescent/adulttrial and the REVEAL Phase 1/2 pediatric trial. Additionally, we advanced discussionswith the United States (U.S.) Food and Drug Administration (FDA) on the regulatorypathway for TSHA-102 and received FDA permission to use our pivotal TSHA-102 productin our REVEAL trials based on the successful demonstration of analytical comparabilitybetween the clinical product and the product derived from the final commercialmanufacturing process. We also strengthened our balance sheet and extended our cashrunway into the fourth quarter of 2026, supporting the continued advancement ofTSHA-102. We believe the progress we have made has set the stage for a highlyimpactful 2025 as we focus on advancing TSHA-102 toward the pivotal phase of theREVEAL trials. Our mission and work are driven by the high unmet medical need that exists in theRett syndrome community. Rett syndrome is a devastating, rare and progressiveneurodevelopmental disease that leads to complications in fine and gross motorfunction, socialization and communication, autonomic function and seizures. Thefunctional impairments and disease features often necessitate 24/7 care and lifelongassistance, leading to a significant caregiver burden and impact on quality of life. There are no approved disease-modifying therapies that treat the genetic root cause ofRett syndrome, which affects an estimated 15,000 to 20,000 patients in the U.S., Europe, and the United Kingdom (U.K.). We believe our differentiated TSHA-102 gene therapycandidate, designed as a one-time treatment that aims to address underlying cause ofthe disease, has the potential to provide meaningful benefit to a broad population ofpatients with Rett syndrome. Encouraging Clinical Data Across Broad Patient Population TSHA-102 is being evaluated in our REVEAL Phase 1/2 adolescent and adult trial takingplace in the U.S. and Canada and our REVEAL Phase 1/2 pediatric trial taking place inthe U.S., Canada and the U.K. We completed dosing of the 10 patients in Part A, the doseescalation portion, of both REVEAL trials. This includes six patients in cohort two, whichis evaluating the high dose of TSHA-102 of 1x1015total vector genomes (vg), and fourpatients in cohort one, which is evaluating the low dose of TSHA-102 of 5.7x1014total vg. Both the high and low dose of TSHA-102 have demonstrated an encouraging safetyprofile. TSHA-102 has been generally well-tolerated with no treatment-related seriousadverse events or dose-limiting toxicities in the 10 pediatric, adolescent and adultpatients dosed as of the February 2025 data cutoff. In June 2024, we presented preliminary clinical data from the adult and pediatricpatients with varying genotypes and disease severity treated in the low dose cohortat the 2024 International Rett Syndrome Foundation (IRSF) Rett Syndrome ScientificMeeting. The data demonstrated early clinical improvements and functional gainsacross multiple domains post-treatment that persisted and strengthened over time. Thisincluded improvements and functional gains across the domains of fine motor, grossmotor, socialization and communication, autonomic function, and seizures. The functional gains consistently achieved following treatment with TSHA-102 are notexpected to occur in the untreated population of patients in the post-regression stageand directly represent improvements in activities of daily living that are meaningful tocaregivers. As such, these outcomes have shaped our interactions with the FDA regardingthe optimal regulatory pathway for TSHA-102. Progress to Solidify Regulatory Pathway From the outset, our strategy has been to utilize Part A of the trials to generate a datasetthat informs our development plan for the pivotal Part B phase of the trials. With dosingof the 10 patients in Part A complete, we believe we have a strong, maturing dataset inhand to further solidify the regulatory pathway for TSHA-102 with the FDA. Based on our ongoing discussions with the FDA and the totality of clinical data generatedto date, our goal is to advance TSHA-102 toward a pivotal trial design that objectivelyassesses functional gains across the key clinical domains impacted in Rett syndrome. InNovember 2024, we announced that following interactions