Taysha Gene Therapies, Inc. · NASDAQ:TSHA
Taysha Gene Therapies — Q2 2025 Earnings Presentation
25 slides from Taysha Gene Therapies's earnings presentation, Aug 12, 2025
Slide 1: Second Quarter 2025 Financial Results and Corporate Update
Second Quarter 2025 Financial Results and Corporate Update August 12, 2025
Slide 2: Legal disclosure
Legal disclosure FORWARD LOOKING STATEMENTS This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding the potential of TSHA-102, the
Slide 3: Agenda
Agenda Opening Remarks and TSHA-102 Sean P. Nolan Regulatory Progress Chairman and Chief Executive Officer Rett Syndrome Natural History Data Suku Nagendran, M.D. Supporting Pivotal Trial Design President and Head of R&D Elsa Rossignol, M.D., FRCP, FAAP Previously Disclosed Part A Data Associate Pro
Slide 4: Recent Highlights
Recent Highlights TSHA-102: designed to address root cause of Rett syndrome, with a clear path to registration High Unmet Need and o No approved therapies address genetic root cause of Rett syndrome Significant Market Opportunity o 15,000-20,000 patients (U.S., EU+U.K.); 1 of 10,000 female births wo
Slide 5: Potential registrational pathway for TSHA-102 for the treatment of females aged 2 years and older with Rett syndrome
Potential registrational pathway for TSHA-102 for the treatment of females aged 2 years and older with Rett syndrome PART A: REVEAL Phase 1/2 Trials PART B: REVEAL Pivotal Trial Potential Registrational Path Dosing complete (N=12 patients, 6-21 years) o Developmental Plateau Population (6 to <22 yea
Slide 6: REVEAL Pivotal Trial for TSHA-102
REVEAL Pivotal Trial for TSHA-102 Commenced site activation following FDA and Health Canada feedback Study Overview Company Believes REVEAL Part A Data o Study Design: Single-arm, open-label trial, using patient as own control Continues to Support Advancement to Pivotal Trial o Dose: 1x1015 total vg
Slide 7: Primary endpoint: milestone gain is an objective, clinically meaningful and individualized assessment
Primary endpoint: milestone gain is an objective, clinically meaningful and inherently individualized assessment of function in the developmental plateau population Gain or regain of ≥ one of 28 defined developmental ~0% probability of milestone gain/regain after age 6 in the untreated population1 m
Slide 8: Longitudinal natural history data informed key elements of TSHA-102 pivotal trial design
Longitudinal natural history data informed key elements of TSHA-102 pivotal trial design Natural History Study (NHS) Dataset1 Developed Age- and Time-Based Models o N = ~1100 females with confirmed Rett syndrome of Developmental Milestone NHS Data1 diagnosis; up to 14 years follow-up o Cumulative in
Slide 9: NHS cumulative incidence models showed likelihood of gaining/regaining 28 milestones is predictable in age ≥6
NHS cumulative incidence models showed that the likelihood of gaining/regaining 28 defined developmental milestones is predictable in the age ≥ 6 population1 Communication Milestones Fine Motor Milestones Gross Motor Milestones Ex: of patients who learn to use word(s) with Ex: of patients who learn
Slide 10: Identified developmental milestones from the NHS dataset for inclusion in the primary endpoint
Identified 28 developmental milestones from the NHS dataset1 for inclusion in the primary endpoint that met predefined criteria Communication Fine Motor Gross Motor o Reached for toy o Pointed for something they wanted o Come to sitting o Holds bottle unpropped o Waved “Bye-Bye” o Sat without suppor
Slide 11: Probability of Gaining/Regaining Developmental Milestones
Rett syndrome NHS data analysis demonstrated that after 6 years of age, there is ~0% likelihood of gaining or regaining developmental milestones1 Graph is for illustrative purposes only and is not derived from natural history data. Probability of Gaining/Regaining By age 6, there is a ~0% The gain o
Slide 12: Rigorous developmental milestone evaluation criteria applied to Part A data
Rigorous developmental milestone evaluation criteria applied to Part A data enabled reliable, objective assessment of TSHA-102 efficacy Relevant developmental milestones data was captured via videos, COAs, caregiver assessments and clinician notes in Part A Developmental milestone evaluation criteri
Slide 13: Elsa Rossignol, M.D., FRCP, FAAP
Elsa Rossignol, M.D., FRCP, FAAP Associate Professor in Neuroscience and Pediatrics at the Université de Montréal, Director of the Rett Multidisciplinary Clinic of the CHU Sainte-Justine Principal Investigator of REVEAL Phase 1/2 Trials
Slide 14: 100% of patients (n=10) gained/regained ≥ one defined developmental milestone post-TSHA-102
100% of patients (n=10) gained/regained ≥ one defined developmental milestone post-TSHA-102 with a ~0% likelihood of being achieved without treatment based on NHS data1 Cohort 1: Low Dose Cohort 2: High Dose 5.7x1014 total vg 1x1015 total vg LD:P1 LD:P2 LD:P3 LD:P4 HD:P1 HD:P2 HD:P3 HD:P4 HD:P5 HD:P
Slide 15: Patients gained/regained developmental milestones across the core functional domains of Rett syndrome
Patients gained/regained developmental milestones across the core functional domains of Rett syndrome post-TSHA-102 A total of 22 developmental milestones were achieved across 10 patients treated with TSHA-102 Communication Fine Motor Gross Motor Spoke in phrases (2 words or more) with meaning Holds
Slide 16: REVEAL caregiver testimonials post-TSHA-102 highlight impact on quality of life
REVEAL caregiver testimonials post-TSHA-102 highlight the impact of functional developmental milestone gains on quality of life “All of our days are better. Her improvements “She’s gained multiple words – ‘no,’ ‘yeah,’ ‘mom,’ ‘dad’ are much beyond anything we had expected – makes consistent sounds w
Slide 17: Accelerated functional benefit seen
High dose TSHA-102 achieved 100% responder result at a 25% faster rate compared to low dose TSHA-102 Responder ResponderRate: Rate:Time to to Time Response Response 100% 75% ⚬ Accelerated functional benefit seen with high dose TSHA-102 50% ⚬ Early clinical response may increase the likelihood of rev
Slide 18: Overview of Revised Motor Behavior Assessment (R-MBA)
Overview of Revised Motor Behavior Assessment (R-MBA) R-MBA Questionnaire Scale ⚬ Clinician-reported assessment that measures the Normal or Never Very Severe or Constant onset of disease regression, growth, motor and 0 1 2 3 4 communication skills, and disease behaviors for Moderate or Occasional in
Slide 19: TSHA-102 demonstrated statistically significant mean R-MBA score improvement compared to natural history
TSHA-102 demonstrated a statistically significant mean R-MBA score improvement compared to natural history at both 6 and 12 months Lower score = improvement; R-MBA assessed in Rett syndrome NHS at ~6 months and ~12 months1 R-MBAR-MBA ScoreScore MeanMean ChangeChange From From Baseline: R-MBA R-MBA S
Slide 20: Overview of Clinical Global Impression-Improvement (CGI-I) rating
Overview of Clinical Global Impression-Improvement (CGI-I) rating with Rett syndrome-specific anchors1 Score CGI-I CGI-I: Clinician-rated scale 1 Very much improved assessing improvement from baseline 2 Much improved o Designed as a global clinical assessment 3 Minimally improved o Factors considere
Slide 21: TSHA-102 demonstrated early global improvement, with dose-dependent effects deepening over time in CGI-I
TSHA-102 demonstrated early global improvement, with dose-dependent effects deepening over time in CGI-I Average CGI-I score of 1.0 (very much improved) in high dose cohort vs. average CGI-I score of 2.8 in low dose cohort at ≥9 months post-TSHA-102 Low Dose: Average 3.0 2.3 3.0 3.3 2.0 CGI-I Score
Slide 22: Consistent dose response observed across key measures
Consistent dose response observed across key measures at 6 months post-TSHA-102, with the separation between dose cohorts increasing over time Endpoint Low Dose Cohort High Dose Cohort Dose-Dependent Response? Responder Rate (%) 100% 100% Developmental by 12 months by 9 months Milestones Responder R
Slide 23: TSHA-102 was generally well tolerated with no treatment-related SAEs or DLTs
TSHA-102 was generally well tolerated at the low and high dose with no treatment-related SAEs or DLTs o All TEAEs related to TSHA-102 were mild- Number of Events Across 12 Pediatric, Adolescent and Adult Patients moderate in severity, with the most common Dosed in Part A of REVEAL Phase 1/2 Trials b
Slide 24: Anticipated TSHA-102 program milestones supported by a strengthened financial position
Anticipated TSHA-102 program milestones supported by a strengthened financial position Fourth Quarter Begin patient enrollment for REVEAL pivotal trial Well-capitalized through 2025 key milestones: o Cash runway expected to fund operating expenses and capital requirements into 2028 Fourth Report new
Slide 25: Question and Answer Session
Question and Answer Session
Taysha Gene Therapies — Q2 2025 Earnings Presentation on 6ix