Taysha Gene Therapies, Inc. · NASDAQ:TSHA
Taysha Gene Therapies — Investor Presentation (August 2026)
43 slides from Taysha Gene Therapies's investor presentation, August 2026
Slide 1: Bringing New Treatments to Life
Bringing New Treatments to Life Corporate Presentation | August 2026
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: Key investment highlights
Key investment highlights TSHA-102: potential one-time treatment 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., E
Slide 4: TSHA-102 Rett syndrome program strongly positioned for rapid execution toward BLA submission
TSHA-102 Rett syndrome program strongly positioned for rapid execution toward BLA submission Compelling Part A Initiated BLA-enabling Potential for Expedited Potential for Broad Clinical Data PPQ Campaign Path to BLA Submission Potential Label Aged for2+ Years Expedited Path supported FDA Breakthrou
Slide 5: Commercial readiness activities designed to position TSHA-102 for successful launch and adoption
Commercial readiness activities designed to position TSHA-102 for successful launch and adoption Market Research Supports Deep Commercial and Intrathecal Administration Potentially Strong Demand, Manufacturing Expertise Enables Broad Access Access and Broad Adoption Seasoned commercial leadership wi
Slide 6: Rett syndrome: a devastating, rare and progressive X-linked neurodevelopmental disease
Rett syndrome: a devastating, rare and progressive X-linked neurodevelopmental disease Primarily occurs in females Caused by mutations in the X-linked gene encoding MeCP2 protein, which inhibits neuronal developments1 Leads to impaired brain development and function, resulting in multisystem complic
Slide 7: Hallmark characteristics of Rett syndrome appear across multiple clinical domains
Hallmark characteristics of Rett syndrome appear across multiple clinical domains impacting activities of daily living Results in loss of functional abilities and developmental milestones and the emergence of hallmark symptoms by 6 years that progress over time1 Gross Motor Fine Motor Communication
Slide 8: No approved disease-modifying treatments address the genetic root cause of Rett syndrome
There are no approved disease-modifying treatments that address the genetic root cause of Rett syndrome High Unmet Medical Need Significant Market Opportunity Current standard of care focused on o ~15,000 to 20,000 patients in major global symptom management1 markets (U.S., EU+U.K.)3 o >85% of preva
Slide 9: Gene Therapy Treatment Challenge: too much or too little MECP2 expression is harmful
Gene Therapy Treatment Challenge: too much or too little MECP2 expression is harmful in Rett syndrome Rett Syndrome Healthy Individual MECP2 Duplication Syndrome WT WT WT WT WT WT WT WT WT WT MECP2 deficiency Normal MECP2 levels Overexpressed MECP2 occurs due to random X-inactivation, leading to in
Slide 10: TSHA-102: an investigational one-time gene therapy designed to regulate MECP2
TSHA-102: an investigational one-time gene therapy that is designed to regulate MECP2 Strategically designed to enable optimal and controlled transgene expression across the CNS Self-complementary miRARE Technology Intrathecal (IT) Delivery miniMECP2 Transgene Vector Regulates transgene Leads to wid
Slide 11: miRARE: potential best-in-class approach to regulating MECP2 expression
miRARE: potential best-in-class approach to regulating MECP2 expression using RNA interference and binding sites for endogenous microRNA responsive to MeCP21 TSHA-102 TSHA-102 1 1 MeCP2 TSHA-102 TSHA-102 3a MeCP2- protein Healthy, deficient cells MeCP2+ cells do not express 2 2 3a express MeCP2 prot
Slide 12: Intrathecal administration: effective, safe and minimally invasive delivery approach
Intrathecal (IT) Administration: a potentially effective, safe and minimally invasive delivery approach for broad targeting of the CNS1 Biodistribution data comparing IT vs. ICM delivery using the same dose and volume in NHPs1 o IT and ICM administration achieved Frontal ns comparable, consistent an
Slide 13: FDA-aligned pathway supports potential 6-month interim registrational strategy
FDA-aligned pathway supports potential 6-month interim registrational strategy PART A: REVEAL Phase 1/2 Trials PART B: REVEAL Pivotal Trial Potential Registrational Path DOSING COMPLETE DOSING COMPLETE Developmental Plateau Population Adolescent and Adult (females ≥12 years) (females 6 to <22 years)
Slide 14: Completed dosing in REVEAL pivotal trial to support BLA submission
Completed dosing in REVEAL pivotal trial for TSHA-102 to support BLA submission – on track to complete 6-month interim analysis Single-arm, open-label trial, using each patient as ⚬ SAP: 33% response rate is the minimum threshold for success sufficient to reject the null hypothesis of 6.7%2 own cont
Slide 15: Key findings that supported alignment with FDA on the REVEAL pivotal trial
Key findings that supported alignment with FDA on the REVEAL pivotal trial 1 Rett Syndrome Caregiver Research achievement of a developmental milestone would be a meaningful therapeutic outcome 2 Rett Syndrome Natural History Data Analysis by age ≥ 6 years, there is ~0% likelihood of gaining or regai
Slide 16: Rett syndrome caregiver research on developmental milestones and quality of life
Rett syndrome caregiver research indicates improved function or achievement of developmental milestones would significantly improve quality of life “If she can actually tell me what Communication she wants, or make a choice between two things, even if it's just Gained or improved communication of ba
Slide 17: Rigorous analysis of the NHS informed REVEAL pivotal trial design
Rigorous analysis of the NHS informed the inclusion criteria and endpoint design for the REVEAL pivotal trial1 Graph is for illustrative purposes only and is not derived from natural history data. Probability of Gaining/Regaining Developmental Milestones Results support minimum inclusion age of 6 y
Slide 18: 28 developmental milestones included in the pivotal trial primary endpoint
28 developmental milestones from the natural history dataset included in the pivotal trial primary endpoint 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 support o Used raking gras
Slide 19: Longer-term REVEAL Part A data demonstrated broad, consistent functional gains
Longer-term REVEAL Part A data demonstrated broad, consistent functional gains that deepened over time regardless of patient age, disease severity or genotype1 ⚬ 100% of patients (N=12, 6-21 years) in the developmental plateau population of Rett gained/regained ≥1 developmental milestone ⚬ Longer-te
Slide 20: Rigorous evaluation criteria applied to Part A data
Rigorous evaluation criteria applied to Part A data enabled reliable, objective assessment of TSHA-102 efficacy Evaluation of Functional Gains Primary evidence of efficacy Additional evidence of functional gain Developmental Milestones (DM) Additional Skills and Improvements The functional gain of ≥
Slide 21: All 12 patients gained/regained at least one developmental milestone
All 12 pediatric, adolescent and adult patients across a broad range of disease severity gained/regained ≥one developmental milestone post-TSHA-102 with a <6.7% likelihood of being achieved without treatment based on NHS data1 Cohort 1: Low Dose Cohort Cohort 1: 14 Low Dose Cohort 2: 2: High High Do
Slide 22: Rapid and robust response rate in REVEAL Part A
Rapid and robust response rate in REVEAL Part A supports the pivotal trial is well-powered to establish efficacy 100% Response Rate 83% (12/12) 75% Response Rate Response Rate (10/12) (9/12) REVEAL Part A data exceeded 33% FDA-aligned response rate threshold FDA-aligned Minimum for pivotal trial suc
Slide 23: 31 total developmental milestones achieved across core disease domains
31 total developmental milestones achieved across core disease domains post-TSHA-102 reflect meaningful improvements in daily living Communication Fine Motor Gross Motor Spoke in phrases with meaning Used utensils to eat without assistance Walked with support Used word(s) with meaning Used utensils
Slide 24: Consistent treatment benefit across pediatric and adolescent/adult patients
TSHA-102 delivered consistent and clinically meaningful treatment benefit across pediatric and adolescent/adult patients with Rett syndrome Results support the broad treatment potential of TSHA-102 16 15 Total Developmental Total Developmental Milestones Achieved Across Milestones Achieved Across 6
Slide 25: Developmental milestone gains across three core disease domains
TSHA-102 drove early and sustained developmental milestone gains with additional gains over time across the three core disease domains Assessed by multiple independent central raters using video-evidenced review in accordance with the pivotal trial criteria # of Developmental Milestones Achieved Tot
Slide 26: Durable skill gains and improvements accumulated over time
Patients achieved durable, clinically meaningful skill gains and improvements that accumulated over time in addition to developmental milestones Total Functional Gains Achieved Post-TSHA-102 Skills/Improvements Achieved Post-TSHA-102 # of Developmental Milestones and Additional 2Skills and Improveme
Slide 27: REVEAL caregiver testimonials highlight impact on quality of life
REVEAL caregiver testimonials post-TSHA-102 highlight the impact of functional gains on quality of life “ She has lots of interest in the world around her. She says what she wants, and we know what she doesn’t! We can negotiate with her – if I ask her if she wants this or that, she’ll respond, ‘no w
Slide 28: 310 total functional gains achieved post-TSHA-102
310 total functional gains achieved post-TSHA-102 highlight its broad functional impact 31 developmental milestones, 279 skill gains and including:1 Walked with support 310 improvements, including:2 Improved motor skills and hand use Climbed down stairs with support Functional Gains Understood and r
Slide 29: Meet Jane, a 21-year-old woman living with Rett syndrome
Meet Jane, a 21-year-old woman living with Rett syndrome Unable to express her Walked independently Non-verbal wants and needs with slow, unsteady Daily to weekly and rarely made No purposeful hand seizures use and very rarely movements, requiring Low interest in choices close supervision social int
Slide 30: Jane achieved sustained, meaningful functional gains
Jane, 21-years-old at dosing, achieved sustained, meaningful functional gains Points to what she Speaks in phrases wants and Improved gait and with meaning consistently makes Consistently uses her mobility with reduced Monthly seizures choices fingers to self-feed bradykinesia Consistently engaged a
Slide 31: Meet Sarah, a 6-year-old girl living with Rett syndrome
Meet Sarah, a 6-year-old girl living with Rett syndrome Used one word with Takes a few steps with assistance Frequent breath- meaning Constant hand Unable to use eating holding and stereotypies with utensils hyperventilation with Rarely responded to limited hand function Required assistance for posi
Slide 32: Sarah achieved sustained, meaningful functional gains
Sarah, 6-years-old at dosing, achieved sustained, meaningful functional gains Can use multiple Reaches 100% Reduced frequency of words of with meaning the time Reduced frequency breath-holding and Pulls herself to a hyperventilation of hand stereotypies Uses utensils to eat standing position and Use
Slide 33: Durable, multi-domain functional gains that enable activities of daily living
TSHA-102 delivered durable, multi-domain functional gains that enable activities of daily living Examples of functional gains observed across the 12 patients post-TSHA-102 Communication improvements Fine motor improvements Gross motor improvements Autonomic/other improvements Pre-TSHA-102 Post-TSHA-
Slide 34: Statistically significant mean R-MBA score improvement
TSHA-102 demonstrated a statistically significant mean R-MBA score improvement indicating a reversal in the disease trajectory Lower R-MBA score is associated with developmental milestone acquisition and quality of life improvement R-MBA Score Mean Change From Baseline in Patients ≥6 Years: REVEAL l
Slide 35: Early global improvement with dose-dependent effects in CGI-I
TSHA-102 demonstrated early global improvement, with dose-dependent effects that deepened over time in CGI-I 100% of Patients Demonstrated an Improved CGI-I Score of <3 at Multiple Post-treatment Visits CGI-I assesses clinician’s impression of improvement from baseline (1 = Very much improved | 7 =
Slide 36: Robust responses at 6 and ≥12 months support potential for BLA submission
Robust and clinically meaningful responses at 6 and ≥12 months support potential for BLA submission based on the 6-month interim analysis from REVEAL pivotal trial 6 Months Post-TSHA-102 12 Months Post-TSHA-102 ≥18 Months Post TSHA-102 Endpoint n=12 n=12 n=7 % of Patients Gained/Regained ≥1 Developm
Slide 37: TSHA-102 generally well-tolerated with no severe treatment-related SAEs or DLTs
TSHA-102 was generally well-tolerated at low and high doses with no severe treatment-related SAEs or DLTs Events Across the 12 Pediatric, Adolescent and Adult Patients Dosed in Part A of REVEAL Phase 1/2 Trials1 o All TEAEs considered related to TSHA-102 were mild-moderate in severity, with the most
Slide 38: Anticipated TSHA-102 program milestones
Anticipated TSHA-102 program milestones Well-capitalized through key milestones: Q4 2026 Complete BLA-enabling PPQ campaign for TSHA-102 o Cash and cash equivalents of $455.4 million as of June 30, 2026 o Cash runway expected to fund Topline data from REVEAL pivotal trial 6-month interim operating e
Slide 39: Appendix
GENE THERAPIES
Slide 40: 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 41: Overview of Revised Motor Behavior Assessment (R-MBA)
Overview of Revised Motor Behavior Assessment (R-MBA) R-MBA Questionnaire Scale Normal or Never Very Severe or Constant ⚬ Clinician-reported assessment that measures the onset of disease regression, growth, motor and 0 1 2 3 4 communication skills, and disease behaviors for Moderate or Occasional in
Slide 42: Preclinical safety, pharmacology, toxicology and biodistribution data
Compelling preclinical safety, pharmacology, toxicology & biodistribution data supported clinical advancement of TSHA-102 in a broad age range of patients TSHA-102 improved survival, TSHA-102 was well tolerated up Broad biodistribution to brain body weight, motor function to 2x1015 vg and spinal cor
Slide 43: Robust preclinical data for TSHA-102 across age ranges
Robust preclinical data for TSHA-102 demonstrated across age ranges HED Route of Species Animal Model Age Study Size Findings: (vg/participant) Administration o Improvement in survival rate, overall neurobehavioral function and Wild-type and Neonates Mouse n=45 2.9x1014 ICV growth in neonatal KO Ret
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