Clinical Trial Application (CTA) approved by
TSHA-102, which utilizes novel miRARE platform to regulate transgene expression genotypically on a cell-by-cell basis, is the first-and-only gene therapy in clinical development for Rett syndrome
TSHA-102 improved survival, respiratory and motor function assessments in mouse models of Rett syndrome; biodistribution in non-human primates (NHP) supports miRARE mechanism of action; six-month NHP GLP toxicology data support the favorable safety and tolerability profile of TSHA-102
Preliminary Phase 1/2 clinical data for TSHA-102 expected by year-end 2022
“Initiation of clinical development is a significant milestone for the TSHA-102 program and Rett syndrome community,” said
Pharmacologic activity of TSHA-102 following intrathecal (IT) administration was assessed in the MECP2 knockout mouse model of Rett syndrome across three dose levels and three age groups (n=252). A one-time IT injection of TSHA-102 significantly increased survival at all dose levels, with the mid to high doses improving survival across all age groups compared to vehicle-treated controls. Treatment with TSHA-102 significantly improved body weight, motor function and respiratory assessments in MECP2 knockout mice. An additional study in neonatal mice is ongoing, and preliminary data suggest normalization of survival.
An IND/CTA-enabling 6-month GLP toxicology study (n=24) examined the biodistribution, toxicological effects and mechanism of action of TSHA-102 when intrathecally administered to NHPs across three dose levels. Biodistribution, as reflected by DNA copy number, was observed in multiple areas of the brain, sections of spinal cord and the dorsal root ganglion (DRG). Importantly, mRNA levels across multiple tissues were low, indicating miRARE regulation is minimizing transgene expression from the construct in the presence of endogenous MECP2 as expected, despite the high levels of DNA that were delivered. No toxicity from transgene overexpression was observed, confirmed by functional and histopathologic evaluations demonstrating no detrimental change in neurobehavioral assessments and no adverse tissue findings on necropsy.
These preclinical safety and efficacy data will be presented at the
About TSHA-102 and miRARE
TSHA-102 is a self-complementary intrathecally delivered AAV9 gene replacement therapy under development for the treatment of Rett syndrome. TSHA-102 utilizes the novel miRNA-Responsive Auto-Regulatory Element (miRARE) platform to regulate transgene expression genotypically on a cell-by-cell basis. The miRARE technology is designed to prevent toxicity associated with transgene overexpression and can be potentially utilized across other indications.
About Rett Syndrome
Rett syndrome is a severe genetic neurodevelopmental disorder caused by a mutation in the X-linked MECP2 gene essential for neuronal and synaptic function in the brain. Primarily occurring in females, Rett syndrome is one of the most common genetic causes of severe intellectual disability worldwide, with a prevalence of over 350,000 patients worldwide2. Patients have normal early development, with symptom onset typically beginning between 6 to 18 months of age. Rett syndrome is characterized by rapid developmental regression that leads to intellectual disabilities, loss of speech, loss of purposeful use of hands, loss of mobility, seizures, cardiac impairments and breathing issues. Currently, there are no approved therapies that treat the underlying cause of this progressive disease.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates,” “believes,” “expects,” “intends,” “projects,” and “future” or similar expressions are intended to identify forward-looking statements. Forward-looking statements include statements concerning the potential of our product candidates, including the TSHA-102 in Rett syndrome, to positively impact quality of life and alter the course of disease in the patients we seek to treat, our research, development and regulatory plans for our product candidates, the potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, these product candidates will be successfully distributed and marketed, and the potential market opportunity for these product candidates. Forward-looking statements are based on management’s current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our
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Chief Corporate Affairs Officer