Taysha Gene Therapies (TSHA) Corporate presentation summary

Disease background and unmet need

• Rett syndrome is a rare, progressive neurodevelopmental disorder primarily affecting females, caused by mutations in the MECP2 gene, leading to multisystem complications and severe impairment in daily living activities.

• Hallmark symptoms include loss of motor and communication skills, epilepsy, autonomic dysfunction, and high caregiver burden.

• No approved therapies address the genetic root cause; current care is symptomatic, with significant unmet medical need and a patient population of 15,000–20,000 in major markets.

TSHA-102 gene therapy overview

• TSHA-102 is a one-time, intrathecally delivered gene therapy using an AAV9 capsid and miRARE technology to regulate MECP2 expression, aiming to correct deficiency without toxic overexpression.

• miRARE enables cell-specific control, silencing transgene in healthy cells and activating it in deficient ones, minimizing risks of over- or under-expression.

• Intrathecal administration achieves broad CNS biodistribution with a minimally invasive, outpatient-friendly procedure.

Clinical development and trial design

• REVEAL Phase 1/2 and pivotal trials enrolled females aged 2–22 years, with dosing complete in both pivotal (N=17) and ASPIRE (N=4) trials.

• Primary endpoint: gain/regain of ≥1 developmental milestone from a validated list of 28, assessed by independent, blinded raters.

• FDA alignment allows for BLA submission based on 6-month interim pivotal data and inclusion of ≥3 months ASPIRE safety data for a broad ≥2 years label.