Taysha Gene Therapies, Inc. · NASDAQ:TSHA
Taysha Gene Therapies — Corporate Update (May 2025)
28 slides from Taysha Gene Therapies's corporate update, May 28, 2025
Slide 1: TSHA-102 Rett Syndrome Program Update May 2025
TSHA-102 Rett Syndrome Program Update May 2025 Exhibit 99.2
Slide 2: Legal disclosure: forward-looking statements
This presentation is intended to be viewed by investors in the U.S. only 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 pr
Slide 3: Agenda
Agenda Rett Syndrome Overview and Natural History Data Analysis FDA Alignment on Key Elements of Pivotal Part B Trial TSHA-102 Clinical Data from Part A of REVEAL Phase 1/2 Trials Developmental Milestones R-MBA CGI-I Safety Data
Slide 4: Key investment highlights
Key investment highlights TSHA-102: potential one-time treatment designed to address the root cause of Rett syndrome 1Amir, R E et al. “Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.” Nature genetics vol. 23,2 (1999): 185-8. doi:partners. 10.1038/13810
Slide 5: Rett Syndrome Overview and Natural History Data Analysis
Rett Syndrome Overview and Natural History Data Analysis Natural History Data accessed from the International Rett Syndrome Foundation (IRSF). We thank IRSF and the governance committee for their partnership.
Slide 6: High caregiver burden and unmet medical need in Rett syndrome
High caregiver burden with significant impact on quality of life and activities of daily living2 Current standard of care focused on symptom management1 There are no approved disease-modifying treatments that address the genetic root cause of Rett syndrome High Unmet Medical Need Significant Market
Slide 7: Caregiver research: developmental milestones would improve quality of life
Rett syndrome caregiver research indicates improved function or achievement of developmental milestones would significantly improve quality of life Communication Fine Motor Function Gained or improved communication of basic needs—through eye gaze, gestures, or words—would enable self-advocacy and st
Slide 8: Natural history data informed pivotal trial design
Longitudinal natural history data informed key elements of TSHA-102 pivotal trial design 1Accessed from International Rett Syndrome Foundation (IRSF). ClinicalTrials.gov: NCT02738281: a prospective cohort of individuals with a pathologic mutation in the MECP2 gene, commonly associated with RTT. Cumu
Slide 9: NHS models: likelihood of gaining/regaining 28 milestones
NHS cumulative incidence models showed that the likelihood of gaining/regaining 28 defined developmental milestones is predictable in the age ≥ 6 population1 1Accessed from International Rett Syndrome Foundation (IRSF). ClinicalTrials.gov: NCT02738281: a prospective cohort of individuals with a path
Slide 10: Identified developmental milestones from the NHS dataset
Identified 28 developmental milestones from the NHS dataset that would reflect: 1Accessed from International Rett Syndrome Foundation (IRSF). ClinicalTrials.gov: NCT02738281: a prospective cohort of individuals with a pathologic mutation in the MECP2 gene, commonly associated with RTT. Cumulative in
Slide 11: ~0% probability of gaining/regaining milestones after age 6
~0% AGE: 0 1 2 3 4 5 10 15 20 25 >30 By age 6, there is a ~0% probability that untreated individuals with Rett syndrome: Gain new milestones Regain milestones that were lost after a defined number of years Probability of Gaining/Regaining Developmental Milestones The gain of new skills or restoratio
Slide 12: Pivotal Part B Trial Design for TSHA-102
Pivotal Part B Trial Design for TSHA-102: data-driven assessment of functional gains in a broad Rett syndrome population
Slide 13: Written FDA alignment on key elements of pivotal Part B REVEAL trial
Obtained written alignment from the FDA on key elements of pivotal Part B REVEAL trial design Study Overview Study Design: Single-arm, open-label trial, using patient as own control Dose: Intend 1x1015 total vg (high dose) Sample Size: Intend 15 females with Rett syndrome age ≥6 years (developmental
Slide 14: Primary endpoint: milestone gain in developmental plateau population
Primary endpoint: milestone gain is an objective, clinically meaningful and inherently individualized assessment of function in the developmental plateau population Supported by cumulative incidence models from longitudinal NHS developmental milestone data Fine motor, gross motor, and communication
Slide 15: TSHA-102 Clinical Data from Part A of REVEAL Phase 1/2 Trials
TSHA-102 Clinical Data from Part A of REVEAL Phase 1/2 Trials
Slide 16: Developmental milestones gained post-TSHA-102 by patient
Based on May 19, 2025, data cutoff (N=10). Data presented reflects current data in the Electronic Data Capture System, subject to change. 1Incidence models derived from NHS data; accessed from International Rett Syndrome Foundation (IRSF). ClinicalTrials.gov: NCT02738281: a prospective cohort of ind
Slide 17: Patients gained/regained milestones across core functional domains
Patients gained/regained developmental milestones across the core functional domains of Rett syndrome post-TSHA-102 Based on May 19, 2025, data cutoff (N=10). Developmental milestone gains and regains were assessed by multiple independent central raters through video evidence. 22 developmental miles
Slide 18: REVEAL caregiver testimonials post-TSHA-102
REVEAL caregiver testimonials post-TSHA-102 highlight the impact of functional developmental milestone gains on quality of life Based on documented testimonials from caregivers of participants treated with TSHA-102 in REVEAL Phase 1/2 trials, as of May 19, 2025, data cutoff. “[Standing while holding
Slide 19: High dose achieved 100% responder result 25% faster than low dose
High dose TSHA-102 achieved 100% responder result at a 25% faster rate compared to low dose TSHA-102 Based on May 19, 2025, data cutoff (N=10). Data presented reflects current data in the Electronic Data Capture System, subject to change. Low Dose N=4 across all time points; High Dose N=6 at 1-3 mon
Slide 20: Overview of Revised Motor Behavior Assessment (R-MBA)
Overview of Revised Motor Behavior Assessment (R-MBA) Clinician-reported assessment that measures the onset of disease regression, growth, motor and communication skills, and disease behaviors for individuals with Rett syndrome1 Associated with developmental milestone acquisition and function impact
Slide 21: R-MBA mean change from baseline vs natural history
Statistical analyses are based on May 19, 2025, data cutoff: TSHA-102 R-MBA mean 6 months: N=9 (Low dose cohort: N=4, High dose cohort: N=5). TSHA-102 R-MBA mean 12 months: N=4, Low dose cohort. 1MBA natural history data converted to R-MBA; mean scores reported were calculated from baseline to 6 and
Slide 22: Overview of Clinical Global Impression-Improvement (CGI-I)
Overview of Clinical Global Impression-Improvement (CGI-I) rating with Rett syndrome-specific anchors1 CGI-I: Clinician-rated scale assessing improvement from baseline Designed as a global clinical assessment Factors considered to determine change included duration, onset, durability of change and t
Slide 23: 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 Based on May 19, 2025, data cutoff. Data presented reflects current data in the Electronic Data Capture System, subject to change. CGI-I average scores based on latest assessment for each patient
Slide 24: Consistent dose response 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? Developmental Milestones Responder Rate (%) 100% by 12 months 100% by 9 months Responder R
Slide 25: 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 Number of Events Across 12 Pediatric, Adolescent and Adult Patients Dosed in Part A of REVEAL Phase 1/2 Trials Low Dose 5.7x1014 vg (N=4) High Dose 1x1015 vg (N=8) Total (N=12) N E N E N E TEAE Rela
Slide 26: Thank you
Thank you May 2025
Slide 27: Appendix
Appendix May 2025
Slide 28: Option Agreement with Astellas
Option Agreement with Astellas In October 2022, we granted Astellas an exclusive option to an exclusive license of certain rights related to TSHA-102 (the “Rett Option”). Subject to certain limited extensions, Astellas may exercise the Rett Option, at its sole discretion, through a specified period