Taysha Gene Therapies, Inc. · NASDAQ:TSHA
Taysha Gene Therapies — Technical Presentation (June 2024)
25 slides from Taysha Gene Therapies's technical presentation, Jun 18, 2024
Slide 1: TSHA-102 in clinical evaluation for Rett syndrome: Cohort one data
TSHA-102 in clinical evaluation for Rett syndrome: Cohort one data from the REVEAL Phase 1/2 Adolescent-Adult and Pediatric trials June 18, 2024 Exhibit 99.2
Slide 2: Forward Looking Statements
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 our strategy, future operations, prospects, pla
Slide 3: Key Takeaway: Encouraging safety profile and improvements across clinical domains
Key Takeaway: Encouraging safety profile and improvements across consistent clinical domains in all four patients treated with the low dose of TSHA-102 support the transformative potential of TSHA-102 No serious adverse events (SAEs) related to TSHA-102 or dose-limiting toxicities (DLTs) observed Ea
Slide 4: Rett syndrome: a rare, progressive neurodevelopmental disease with high unmet medical need
Rett syndrome: a rare, progressive neurodevelopmental disease with high unmet medical need Caused by mutations in the X-linked gene encoding MeCP21 Leads to impaired brain development and function Primarily occurs in females Symptoms and severity vary due in part to random X-inactivation2 Significan
Slide 5: TSHA-102: an investigational one-time gene therapy for Rett syndrome
TSHA-102: an investigational one-time gene therapy for Rett syndrome that is designed to regulate MECP2 on a cell-by-cell basis TSHA-102 delivers a functional form of MECP2 to cells in the central nervous system (CNS) Equipped with novel miRNA-responsive target sequence (miRARE) designed to mediate
Slide 6: Adolescent-adult REVEAL trial design for TSHA-102
Open-label, dose-escalation and dose-expansion, randomized, multi-center trial for TSHA-102 Clinical trial: NCT05606614; MAD: maximum administered dose; MTD: maximum tolerated dose Cohort 1 5.7x1014 total vg Cohort 2 1x1015 total vg Cohort 3 MAD/MTD Part A: Dose Escalation Part B: Dose Expansion Ado
Slide 7: Encouraging safety profile and improvements observed through longer-term assessments in adult patients
Encouraging safety profile and improvements across consistent clinical domains observed through longer-term assessments in both adult patients in low dose cohort No SAEs related to TSHA-102 or DLTs as of week 52 assessment (patient one) and week 36 assessment (patient two) Generally well-tolerated I
Slide 8: Both adult patients had stage four Rett syndrome with different mutation severity
Both adult patients dosed in low dose cohort had stage four Rett syndrome with different genetic mutation severity and phenotypic expression Source: Company data | baseline characteristics based on pre-treatment observations, baseline assessments, pre-screening visits and patient’s medical history.
Slide 9: Sustained and new improvements across multiple clinical domains in adult patients
Sustained and new improvements seen across multiple clinical domains in both adult patients based on clinical observations reported by Principal Investigator Clinical Domain Improvements Adult Patient One 52 weeks post-treatment Completed steroid taper week 36 and sirolimus taper week 43 Adult Patie
Slide 10: Sustained and new improvements in adult patients per Principal Investigator
Sustained and new improvements seen across multiple clinical domains in both adult patients based on clinical observations from Principal Investigator Mostly non-verbal Adult Patient One 20-year-old female (large MECP2 deletion; severe phenotype) Seizures Complete loss of ambulation and ability to s
Slide 11: Clinical improvements across multiple efficacy measures in both adult patients
Clinical improvements demonstrated across multiple efficacy measures in both adult patients treated with TSHA-102 (low dose, 5.7x1014 total vg) Data presented reflects current data in the Electronic Data Capture System, subject to change CGI-S CGI-I, with Rett anchors PGI-I RSBQ R-MBA RSHFS RSHFS Sc
Slide 12: Pediatric REVEAL trial design for TSHA-102
Open-label, dose-escalation and dose-expansion, randomized, multi-center trial for TSHA-102 Study Overview Objectives Safety and preliminary efficacy of TSHA-102 Part A: evaluates two dose levels; if possible, establishes the MAD or MTD Part B: evaluates the MAD or MTD in two age cohorts Key inclusi
Slide 13: Encouraging safety and initial clinical improvements in first two pediatric patients
Encouraging safety profiles and initial clinical improvements observed across multiple domains in first two pediatric patients dosed in low dose cohort No SAEs related to TSHA-102 or DLTs as of week 22 assessment (patient one) and week 11 assessment (patient two)* Generally well-tolerated Improvemen
Slide 14: First two pediatric patients with stage three Rett syndrome baseline characteristics
First two pediatric patients with stage three Rett syndrome in low dose cohort had different genetic mutation severity and phenotypic expression Baseline Characteristics Pediatric Patient One Pediatric Patient Two Diagnosed with stage three “pseudo stationary” Rett syndrome 6 year-old female 7 year-
Slide 15: Improvements across multiple clinical domains in both pediatric patients
Clinical observations made by the Principal Investigator are based on post-treatment assessments, pre-treatment observations, baseline assessments, pre-screening visits and patient’s medical history. Subject to change as the trial progresses. Improvements seen across multiple clinical domains in bot
Slide 16: Early evidence of developmental gains in both pediatric patients
Early evidence of developmental gains in both pediatric patients based on clinical data and observations from Principal Investigator Pediatric Patient One 6-year-old female (MECP2 deletion; moderate phenotype) Patient history 12 weeks post-TSHA-102 AUTONOMIC FUNCTION: Improved breathing patterns COM
Slide 17: Pediatric efficacy scales: CGI-S, CGI-I, PGI-I, RSBQ, R-MBA, MSEL-A, RSHFS
CGI-S CGI-I, with Rett anchors PGI-I RSBQ R-MBA MSEL-A RSHFS Scale Description Clinician-reported 7-point assessment of illness severity 1=normal 7=among the most extremely ill Clinician-reported 7-point assessment of overall improvement 1=very much improved 7=very much worse Caregiver-reported 7-po
Slide 18: MSEL-A: Pediatric patient one showed new developmental gains
MSEL-A: Pediatric patient one showed new developmental gains in visual reception, receptive language and fine motor skills at week 12 Adapted Mullen Scales of Early Learning (MSEL-A): Standardized cognitive developmental assessment adapted for patients with Rett syndrome that functionally evaluates
Slide 19: Improvements across consistent clinical domains in all patients treated with low-dose TSHA-102
Improvements across consistent clinical domains in all patients treated with low-dose TSHA-102 based on clinician and caregiver assessments and video evidence
Slide 20: Progress in clinical-stage TSHA-102 program across a broad range of ages and stages
Progress in clinical-stage TSHA-102 program supports clinical evaluation across a broad range of ages and stages of Rett syndrome Completed dosing of Cohort 1 (low dose, n=2); encouraging longer-term safety and efficacy data* Expanded trial to include patients ≥12 years of age Dosed first patient in
Slide 21: Anticipated TSHA-102 2024 program milestones
Third quarter of 2024 Dose first patient in cohort two (high dose, n=3) of 1x1015 total vg in REVEAL Phase 1/2 pediatric trial Second half of 2024 Report initial safety and efficacy data from cohort two (high dose) of 1x1015 in both REVEAL trials Anticipated TSHA-102 2024 program milestones
Slide 22: Q&A
Q&A Taysha
Slide 23: Thank You
Thank You investors@tayshagtx.com
Slide 24: Appendix
Appendix e1etee! GENE THERAPIES
Slide 25: Safety summary and relatedness assessments
Safety summary and relatedness assessments In these clinical trials, TSHA-102 has been well-tolerated, with a total of 34** treatment-emergent adverse events (TEAEs). Of these, 33 were mild or moderate. One serious adverse event (SAE), seizure (severe, grade 3), has been reported, unrelated to TSHA-
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