Taysha Gene Therapies (TSHA) Status Update summary

Program and Clinical Trial Overview

• TSHA-102 is a one-time, intrathecally delivered gene therapy using miRARE technology to regulate MECP2 expression, targeting the genetic root cause of Rett syndrome.

• The REVEAL Phase 1/2 trials are open-label, randomized, dose-escalation and expansion studies in the U.S., Canada, and U.K., enrolling adolescent, adult, and pediatric females with MECP2 loss-of-function mutations.

• Regulatory designations include RMAT, ODD, RPDD, and FTD from the FDA, ODD from EMA, and ILAP from MHRA.

• No approved disease-modifying therapies exist for Rett syndrome, which affects 15,000–20,000 patients in major global markets.

• Significant data from both low and high dose cohorts are expected in the second half of 2024.

Disease Background and Market Opportunity

• Rett syndrome is a rare, progressive neurodevelopmental disorder caused by MECP2 mutations, primarily affecting females.

• Symptoms include impaired brain development, motor and communication deficits, autonomic dysfunction, and seizures.

• High unmet need exists due to lack of disease-modifying therapies.

• Estimated prevalence is 15,000–20,000 patients in the US, EU, and UK.

Efficacy and Clinical Improvements: Adult/Adolescent Cohort

• Two adult patients with different MECP2 mutations (severe and moderate phenotypes) showed sustained improvements in motor skills, communication, socialization, autonomic function, and seizure control up to 52 and 25 weeks post-treatment.

• Patient one regained ability to sit unassisted after a decade, improved hand function, sleep, and had well-controlled seizures at lower medication levels.

• Patient two showed reduced hand stereotypies, improved posture, increased social interest, and was seizure-free for 8.5 months with reduced medication.

• Improvements were reflected in clinician and caregiver assessments across multiple standardized scales (CGI-S, CGI-I, PGI-I, RSBQ, R-MBA).

• No serious adverse events or dose-limiting toxicities related to TSHA-102 observed in adults up to 52 weeks.