NGN-401 Clinical Development and Trial Design - NGN-401 is being developed as a potential one-time, best-in-class gene therapy for Rett syndrome, showing durable multidomain improvements across the disease spectrum[8] - The Embolden registrational trial, aligned with the FDA, is a single trial for ages ≥ 3 years, with multiple participants dosed in 4Q'25[8] - The Embolden trial is a single-arm, baseline-controlled, open-label trial of NGN-401 in females with Rett Syndrome, using a one-time 1E15 vg dose in patients ≥ 3 years[30, 31] - The primary endpoint for the Embolden trial at 12 months is a responder-based composite endpoint, requiring a 35% response rate (7 of 20 participants) for success[32] Market Opportunity and Commercial Readiness - Rett syndrome presents a multi-billion-dollar market opportunity for disease-modifying gene therapy, with an estimated prevalence of ~15,000 – 20,000 patients in major markets (US, EU, and UK)[9, 13] - Payors are receptive to reimbursement for Rett syndrome treatments, valuing functional changes that are clinically meaningful and show improvements in activities of daily living[13] - Early commercial-readiness activities are underway, including positioning Embolden clinical trial sites for rapid conversion to commercial sites at launch[9, 42] Phase 1/2 Clinical Trial Data - Interim Phase 1/2 data showed 100% of participants demonstrated functional improvements across core disease domains (fine motor/hand function, gross motor/ambulation, and communication)[24] - A total of 35 developmental milestones were gained in the Phase 1/2 trial, with no plateau observed out to 24 months[24] - In the Phase 1/2 trial, 88% of participants achieved an improved CGI-I score[24] Upcoming Milestones and Financial Position - Complete dosing of the Embolden trial is expected in 2Q'26, with presentation of 12+ months Phase 1/2 data for all 10 participants planned for mid-2026[10] - The company has a strong cash balance expected to fund operations through Embolden data readout, BLA submission, and key pre-launch activities (as of 1Q'28)[49]

EVERY BREAKTHROUGH BEGINS WITH BELIEF January 2026 Corporate Presentation Disclaimer Forward Looking Statements This communication contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current expectations and beliefs of the management of Neurogene, as well as assumptions made by, and ...

Core Insights - Taysha Gene Therapies has initiated dosing in the REVEAL pivotal trial for TSHA-102, a gene therapy for Rett syndrome, with the first patient dosed in Q4 2025 and enrollment progressing across multiple sites [1][2] - The company has reached written alignment with the FDA regarding the inclusion of at least three months of safety data from the ASPIRE trial in the planned Biologics License Application (BLA) submission, aiming for a broad label for patients aged two years and older with Rett syndrome [2][5] - Completion of dosing in both the REVEAL and ASPIRE trials is anticipated by Q2 2026, with longer-term safety and efficacy data updates expected in H1 2026 [1][6] Company Overview - Taysha Gene Therapies is a clinical-stage biotechnology company focused on developing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases affecting the central nervous system [9] - The lead program, TSHA-102, is designed as a one-time treatment targeting the genetic root cause of Rett syndrome by delivering a functional form of the MECP2 gene [7] - The company has received multiple designations from the FDA, including Breakthrough Therapy and Fast Track, indicating its potential significance in addressing unmet medical needs [7] Disease Context - Rett syndrome is a rare neurodevelopmental disorder primarily affecting females, characterized by severe developmental regression and loss of motor and communication skills [8] - It is estimated that between 15,000 and 20,000 patients in the U.S., EU, and U.K. are affected by Rett syndrome, highlighting a significant market opportunity for effective treatments [2][8]

Core Insights - Taysha Gene Therapies announced a 100% response rate in a pivotal trial for TSHA-102, with all 10 patients gaining or regaining at least one developmental milestone as defined by natural history data [1][3] - A supplemental analysis revealed that 100% of patients demonstrated multiple skill gains beyond the predefined milestones, indicating broad functional improvements [1][3] - The findings highlight significant functional gains across 22 developmental milestones and 165 additional skills, impacting daily living activities [1][3] Company Overview - Taysha Gene Therapies is a clinical-stage biotechnology company focused on AAV-based gene therapies for severe monogenic diseases of the CNS, with TSHA-102 being developed for Rett syndrome [5][7] - TSHA-102 is designed as a one-time treatment to address the genetic root cause of Rett syndrome by delivering a functional form of MECP2 to CNS cells [5] - The company has received multiple designations from the FDA, including Breakthrough Therapy and Fast Track, indicating its potential significance in treating Rett syndrome [5] Disease Context - Rett syndrome is a rare neurodevelopmental disorder primarily affecting females, characterized by loss of communication and motor functions, and is caused by mutations in the MECP2 gene [6] - The disorder affects an estimated 15,000 to 20,000 patients in the U.S., EU, and U.K., with no approved therapies targeting the genetic cause [6]

Core Insights - Taysha Gene Therapies has commenced site activation for the REVEAL pivotal trial, with patient enrollment expected to begin in Q4 2025 following regulatory feedback from Health Canada and the FDA [1][3][4] - The TSHA-102 treatment has shown a 100% response rate in the primary endpoint of gaining or regaining developmental milestones in the Phase 1/2 trials, indicating strong therapeutic potential [1][5][10] - The company has successfully raised $230 million through a public follow-on offering, extending its cash runway into 2028 [1][8] Company Updates - Taysha Gene Therapies is focused on advancing AAV-based gene therapies for severe monogenic diseases, particularly targeting Rett syndrome with its lead product TSHA-102 [2][12] - The REVEAL pivotal trial is designed as a single-arm, open-label study, with a primary endpoint assessing the percentage of patients who gain or regain developmental milestones [4][5] - The company has received various designations from the FDA, including Regenerative Medicine Advanced Therapy and Fast Track, which facilitate the development of TSHA-102 [10][12] Financial Performance - For Q2 2025, Taysha reported a net loss of $26.9 million, compared to a net loss of $20.9 million in Q2 2024, with research and development expenses increasing to $20.1 million [7][15] - Cash and cash equivalents as of June 30, 2025, were $312.8 million, bolstered by the recent follow-on offering [8][16] - General and administrative expenses rose to $8.6 million in Q2 2025, primarily due to higher legal and professional fees [6][15]

Core Insights - Taysha Gene Therapies is advancing its TSHA-102 program for Rett syndrome, focusing on the potential to improve developmental milestones and quality of life for patients [2][3] - The company will present recent updates on TSHA-102 at the 2025 International Rett Syndrome Foundation Scientific Meeting in Boston [2][4] - TSHA-102 is a gene therapy designed to address the genetic root cause of Rett syndrome by delivering a functional form of the MECP2 gene [5] Company Overview - Taysha Gene Therapies is a clinical-stage biotechnology company specializing in AAV-based gene therapies for severe monogenic diseases of the central nervous system [7] - The company has received multiple designations from the FDA for TSHA-102, including Regenerative Medicine Advanced Therapy and Fast Track designations [5] - Taysha aims to address significant unmet medical needs in the field of gene therapy, leveraging its experienced management team and proven AAV9 capsid technology [7] Disease Context - Rett syndrome is a rare neurodevelopmental disorder primarily affecting females, characterized by loss of communication, motor function, and intellectual disabilities [6] - The disorder is caused by mutations in the MECP2 gene, with an estimated 15,000 to 20,000 patients affected in the U.S., EU, and U.K. [6] - Currently, there are no approved therapies that modify the disease's genetic root cause, highlighting the importance of TSHA-102 [6]

Core Insights - Taysha Gene Therapies announced positive clinical data for TSHA-102, a gene therapy for Rett syndrome, showing a 100% responder rate in patients aged 6-21 years, with all patients gaining or regaining at least one developmental milestone post-treatment [1][2][5] - The FDA has provided written alignment on the pivotal Part B trial design for TSHA-102, which is expected to begin in Q3 2025 [1][4][12] - The analysis of natural history data indicates that patients aged six years and older are in a developmental plateau, with a likelihood of gaining new milestones being exceedingly low without treatment [1][6] Company Overview - Taysha Gene Therapies is a clinical-stage biotechnology company focused on AAV-based gene therapies for severe monogenic diseases of the CNS, with TSHA-102 as its lead program targeting Rett syndrome [8][10] - TSHA-102 is designed as a one-time treatment that delivers a functional form of the MECP2 gene to address the genetic root cause of Rett syndrome [8][9] Clinical Trial Details - The pivotal Part B trial will be a single-arm, open-label study with an intended enrollment of 15 patients, assessing developmental milestone gain/regain [1][6] - The primary endpoint of the trial is the gain or regain of at least one defined developmental milestone, with independent central raters evaluating outcomes based on video evidence [6] - Safety data from the ongoing REVEAL Phase 1/2 trials indicated no treatment-related serious adverse events or dose-limiting toxicities [1][5][6] Efficacy and Safety Findings - In the REVEAL Part A trial, 100% of patients treated with TSHA-102 achieved developmental milestones, with high-dose cohorts showing faster and more pronounced improvements compared to low-dose cohorts [1][5][6] - Improvements were observed across multiple clinician-assessed outcome measures, including the Revised Motor Behavior Assessment and Clinician Global Impression – Improvement [6] Future Plans - The company plans to submit the pivotal trial protocol and statistical analysis plan as an amendment to the IND application within the current quarter [2][12] - Taysha anticipates initiating pivotal trial activities in Q3 2025, following FDA guidance [1][12]

Core Insights - Taysha Gene Therapies has made significant regulatory and clinical progress with its TSHA-102 program for Rett syndrome, having reached alignment with the FDA on key elements of the pivotal Part B trial design [3][4] - The FDA has advised the company to submit the pivotal Part B trial protocol and statistical analysis plan as an amendment to the IND application, which is expected to expedite study initiation and registration [3][4] - TSHA-102 has shown to be generally well tolerated in patients, with no treatment-related serious adverse events or dose-limiting toxicities reported in the initial cohorts [4] Regulatory Progress - The company achieved alignment with the FDA on the pivotal Part B trial design for TSHA-102, following discussions under the Regenerative Medicine Advanced Therapy (RMAT) pathway [4] - The FDA's guidance allows Taysha to submit the trial protocol directly as an IND amendment, eliminating the need for a formal end-of-phase meeting, which may accelerate the process [3][4] Clinical Data - As of April 10, 2025, TSHA-102 has been administered to 10 patients (6 in the high dose cohort and 4 in the low dose cohort) across two REVEAL Phase 1/2 trials, with no serious adverse events or dose-limiting toxicities reported [4] - A comprehensive update on the pivotal trial design, natural history data analysis, and clinical data from the REVEAL trials is anticipated in Q2 2025 [4][13] Financial Highlights - For Q1 2025, research and development expenses were $15.6 million, down from $20.7 million in Q1 2024, primarily due to reduced manufacturing activities [7] - General and administrative expenses increased to $8.2 million in Q1 2025 from $7.1 million in Q1 2024, attributed to higher compensation and legal fees [8] - The net loss for Q1 2025 was $21.5 million, or $0.08 per share, compared to a net loss of $24.1 million, or $0.10 per share, in Q1 2024 [9][17] Cash Position - As of March 31, 2025, Taysha had $116.6 million in cash and cash equivalents, which is expected to support operations into Q4 2026 [9][19] Upcoming Events - Taysha will present three abstracts related to TSHA-102 at the 2025 International Rett Syndrome Foundation Scientific Meeting scheduled for June 9-11, 2025 [4][5]