Exhibit 99.1
Taysha Gene Therapies Presents Preclinical Data on TSHA-102 for Rett Syndrome Demonstrating Cellular Regulation of MeCP2 Expression in Key Mouse Models at the American Society of Gene and Cell Therapy 26th Annual Meeting
New preclinical data after neonatal administration in wild-type mice showed no detectable impact on survival, neurobehavioral functions and overall health, suggesting TSHA-102, engineered with novel miRARE technology, avoided toxic overexpression of MeCP2 within cells already expressing MeCP2
Data reinforce previous findings in Mecp2–/Y knockout mice demonstrating TSHA-102 regulated cellular MeCP2 levels and significantly improved survival, overall neurobehavioral function and growth
Data in neonatal mouse models highlight the potential of the miRARE technology to enable safe expression levels of MeCP2, which may address the risks associated with both under and overexpression of MeCP2 resulting from the mosaic pattern of MECP2 silencing in females with Rett syndrome
Dosing of the first adult patient with TSHA-102 in the Phase 1/2 REVEAL trial in Rett syndrome is expected in Q2 2023
DALLAS – May 19, 2023 – Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a clinical-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (CNS), today presents preclinical data from neonatal mouse models on TSHA-102 for Rett syndrome, including new data in wild-type mice, at the American Society of Gene and Cell Therapy (ASGCT) 26th Annual Meeting. TSHA-102 utilizes a miniMECP2 gene and a novel miRNA-Responsive Auto-Regulatory Element (miRARE) technology designed to regulate cellular MECP2 expression. In a Taysha-sponsored study, the safety and efficacy of TSHA-102 were explored in both neonatal wild-type and Mecp2–/Y knockout mice, respectively. Preclinical in-life data on early intervention of TSHA-102 in neonatal mice suggest miRARE enables the expression of the MeCP2 protein in deficient CNS cells while preventing toxic overexpression within cells expressing normal levels of MeCP2.
“These encouraging new preclinical data in wild-type mice indicate that TSHA-102, engineered with our miRARE technology, avoided overexpression of MeCP2 within cells already expressing MeCP2, while maintaining normal survival, neurobehavioral function and overall health,” said Sukumar Nagendran, M.D., President, and Head of R&D. “These new data augment previous findings in the Mecp2–/Y knockout mouse model, suggesting that THSA-102 regulated expression of MECP2 in both normal and MECP2 deficient cells, which is critical given that Rett syndrome represents such a challenging case for human gene therapy because the therapeutic window for MECP2 transgene expression is narrow. Either MECP2 deficiency or duplication can lead to serious neurodevelopmental disease. We believe these new data from neonatal wild-type mice support the potential of miRARE to enable the optimal amount of MeCP2. This would be critical to modulating the cellular expression of MeCP2 in an appropriate, clinically relevant manner, given the mosaic pattern of MECP2 silencing characteristic of female patients with Rett syndrome.”
Sarah Sinnett, Ph.D., University of Texas Southwestern Medical Center, Co-Inventor of miRARE technology, added, “TSHA-102 pairs a therapeutic gene with miRARE, all within a single vector genome. The miRARE technology was designed to mitigate the risk of MeCP2 overexpression through a post-transcriptional feedback repression mechanism. We are pleased that miRARE permitted efficacy in Mecp2–/Y mice without compromising safety in wild-type mice. Importantly, these findings could translate into clinical benefits for treating patients with Rett syndrome.”
