Taysha Gene Therapies reports initial data from REVEAL Phase 1/2 trial

TSHA-102 in Rett syndrome: a self-complementary intrathecally delivered AAV9 gene transfer therapy in clinical evaluation for Rett syndrome, a rare genetic neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene. TSHA-102 utilizes a novel miRARE platform designed to mediate levels of MECP2 in the CNS on a cell-by-cell basis without risk of overexpression. TSHA-102 has received Orphan Drug and Rare Pediatric Disease designations from the FDA and has been granted Orphan Drug designation from the European Commission. TSHA-102 is being evaluated in the REVEAL Phase 1/2 trial, a first-in-human, open-label, randomized, dose-escalation and dose-expansion study evaluating the safety and preliminary efficacy of TSHA-102 in adult females with Rett syndrome due to MECP2 loss-of-function mutation. Primary efficacy endpoints are patient assessments by clinicians using the Clinical Global Impressions Scale – Improvement, Rett Syndrome Hand Function Scale, and Revised Motor Behavior Assessment. Secondary endpoints include patient assessments by clinicians and caregivers using the Clinical Global Impressions Scale – Severity, the Rett Syndrome Behavior Questionnaire and other clinical assessment scales. Results from the first adult patient dosed in cohort one with TSHA-102 in the REVEAL Phase 1/2 trial: Well-tolerated safety profile with no treatment-emergent SAEs as of six-week assessment post-treatment. The following were demonstrated in key efficacy measures four weeks post-treatment: Clinical Global Impressions – Improvement scale adapted to Rett syndrome, a clinician-reported assessment of overall improvement using a seven-point scale, demonstrated a score of two indicating “much improved”; Clinical Global Impressions – Severity scale, a clinician-reported assessment of overall severity of a patient’s illness using a seven-point scale, demonstrated a one-point improvement from the baseline score of six to a score of five; Rett Syndrome Behavior Questionnaire, a 45-item questionnaire to assess Rett syndrome characteristics, demonstrated a total score improvement of 23 points from the baseline score of 52 to a score of 29; Seizure diary demonstrated no quantifiable seizure events through week five post-treatment; No marked changes observed four weeks post-treatment in the Revised Motor Behavior Assessment, a 24-question clinician-reported scale measuring disease behaviors of Rett syndrome; Initial efficacy data and clinical observations supported by video evidence from PI six-weeks post-treatment indicate clinical improvements in multiple domains, including: Autonomic function with improvements in breathing patterns and sleep quality/duration, including the normalization of night-time behavior; Vocalization with increased social interest; Gross motor skills with the gained ability to sit unassisted for three minutes; Fine motor skills and hand function with the gained ability to hold an object, unclasp her hands and use her fingers to touch a screen; Further updates on available clinical data expected quarterly; Dosing of second patient cleared by the Independent Data Monitoring Committee and expected in Q3 2023, with continued dosing of adult patients in second half of 2023; U.S. FDA cleared the IND application for TSHA-102 in pediatric patients with Rett syndrome; CTA submitted to U.K. MHRA for TSHA-102 in pediatric patients with Rett syndrome