Taysha Gene Therapies, Inc. · NASDAQ:TSHA
Taysha Gene Therapies — Q1 2026 Earnings Presentation
41 slides from Taysha Gene Therapies's earnings presentation, May 6, 2026
Slide 1: Bringing New Treatments to Life
Bringing New Treatments to Life Corporate Presentation | May 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 Seasoned Commercial Intrathecal Administration Potentially Strong Demand Leadership Team Enables Broad Access and Broad Adoption1 Deep expertise across gene therapy High clinicia
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 Estimated 15,000 and 20,000 patients in symptom management1 major global markets (U.S., EU+U.K.)3 Patie
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: a potentially 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 to potential registration for TSHA-102
FDA aligned pathway to potential registration for TSHA-102 PART A: REVEAL Phase 1/2 Trials PART B: REVEAL Pivotal Trial Potential Registrational Path Adolescent and Adult (females ≥12 years) Developmental Plateau Population (females 6 to <22 years) Patients with Cohort 2 o Evaluate efficacy and safe
Slide 14: Ongoing REVEAL Pivotal Trial for TSHA-102
Ongoing REVEAL Pivotal Trial for TSHA-102 Finalized FDA alignment on study protocol and SAP Study Overview o Study Design: Single-arm, open-label trial, using each patient as own control o Dose: 1x1015 total vg (high dose), administered intrathecally Company Believes REVEAL Part A Data Support Pivot
Slide 15: Primary endpoint: milestone gain is an objective, clinically meaningful 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 probability of milestone gain/regain ~0% after age 6 in the untreated population1 m
Slide 16: 28 developmental milestones included in the primary endpoint
28 developmental milestones from the natural history dataset included in the 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 grasp to retrieve
Slide 17: 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 18: 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 19: Longitudinal natural history data informed key elements of 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 of o N = ~1100 females with confirmed Rett syndrome Developmental Milestone NHS Data1 diagnosis; up to 14 years follow-up o Cumulative in
Slide 20: NHS cumulative incidence models: milestone gain predictable in age ≥6 population
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 21: After age 6, ~0% likelihood of gaining or 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. NHS data analysis Probability of Gaining/Regaining By age 6, there i
Slide 22: REVEAL Part A data supports safety profile and disease-modifying potential of TSHA-102
REVEAL Part A data supports encouraging safety profile and disease-modifying potential of TSHA-1021 Underscores the potential to improve function and enable developmental milestone achievements Generally no treatment-related SAEs or DLTs in all patients treated to date Well-tolerated Developmental i
Slide 23: Part A of REVEAL Phase 1/2 trials of TSHA-102
Part A of REVEAL Phase 1/2 trials of TSHA-102 Dosing complete (N=12, aged 6-21 years) Adolescent and Adult Trial Females aged ≥12 years High dose Study overview: Low dose o Open-label, dose-escalation and dose-expansion Cohort 2 trial in the U.S. and Canada 1x1015 total vg Cohort 1 o Safety and prel
Slide 24: 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 Developmental milestones data was captured via videos, COAs, caregiver assessments and clinician notes in Part A Developmental milestone evaluation criteria: ✓ Base
Slide 25: 100% of patients (N=10) gained/regained ≥ one developmental milestone
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 26: Milestones gained/regained across 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 27: High dose achieved 100% responder result at a faster rate than low dose
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 28: REVEAL caregiver testimonials post-TSHA-102
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 29: Systematic evaluation criteria in Part A demonstrated broad functional impact
Systematic evaluation criteria in Part A demonstrated a broad functional impact of TSHA-102 Primary Evidence of Efficacy Supportive Evidence of Functional Gain Developmental Milestones (DM) Additional Skills and Improvements Functional gain of ≥ one of the 28 DMs defined Functional gain or improveme
Slide 30: 100% of patients achieved multiple skills/improvements outside defined milestones
100% of patients (N=10) achieved multiple skills/improvements outside the natural history defined developmental milestones post-TSHA-102 Reinforce broad, consistent functional gains across the core domains impacting activities of daily living A Total of 165 Additional Skills and Improvements Achieve
Slide 31: Examples of multi-domain functional gains and improvements post-TSHA-102
Examples of multi-domain functional gains and improvements impacting activities of daily living observed post-TSHA-102 Based on developmental milestone gains and additional skills/improvements among the 10 treated patients1 Communication Fine Motor Gross Motor Autonomic / Other Improvements Improvem
Slide 32: Statistically significant mean R-MBA score improvement versus 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 33: Early global improvement with dose-dependent effects 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 34: 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 35: TSHA-102 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 36: Anticipated TSHA-102 program milestones
Anticipated TSHA-102 program milestones Q2 2026 Complete dosing in REVEAL pivotal trial Well-capitalized through key milestones: Q2 2026 Complete dosing in ASPIRE trial o Cash and cash equivalents of $276.6 million as of March 31, 2026 Report longer-term safety and efficacy data from o Cash runway e
Slide 37: Appendix
GENE THERAPIES
Slide 38: 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 39: 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 40: Preclinical safety, pharmacology, toxicology and biodistribution data supported clinical advancement
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 41: Robust preclinical data for TSHA-102 demonstrated 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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