NEW YORK – Taysha Gene Therapies on Wednesday shared new data on its adeno-associated virus serotype 9 (AAV9)-based gene therapy candidates, TSHA-120 for giant axonal neuropathy (GAN) and TSHA-102 for Rett syndrome, and outlined regulatory plans for each drug.
TSHA-120 is an AAV9 self-complementary viral vector that delivers a functional copy of the GAN gene to drive expression of the protein it encodes. TSHA-102 is a gene transfer therapy that uses a novel miRNA-Responsive Auto-Regulatory Element platform to modulate cellular MECP2 expression.
Taysha received feedback from the US Food and Drug Administration on TSHA-120 last year that it needed to address patient heterogeneity in terms of disease progression in giant axonal neuropathy and concerns about using motor function measure 32 (MFM32) as an endpoint. After the agency signaled it would be open to alternative study designs, Taysha analyzed the available data on TSHA-120 to identify a regulatory path forward for the drug.
In a Phase I trial, Taysha investigators tested an escalating single dose of TSHA-120 administered intrathecally in patients with genetically confirmed GAN. In January 2022, the Dallas-based company reported positive clinical efficacy and safety data in the high-dose patient cohort based on a change in the rate of decline in MFM32.
In the new analysis, Taysha developed a disease progression model using functional, electrophysiological, and biological endpoints that show a clinically meaningful treatment effect. "Our newly developed disease progression model demonstrates predictable and homogenous disease progression in classic GAN, which in our view supports the use of natural history data as an external control," Taysha CEO Sean Nolan said in a statement. According to Nolan, the company has requested a formal meeting with the FDA to discuss these new developments and solidify regulatory plans for TSHA-120; the company expects to meet with the agency in Q3.
For TSHA-102, Taysha said it has dosed the first patient in the REVEAL Phase I/II trial and identified a second patient for treatment in the study. Sukumar Nagendran, Taysha president and head of R&D, said in a statement that the company is "encouraged" by initial clinical observations of that first patient and that the firm is on track to submit a clinical trial application to the UK Medicines and Healthcare Products Regulatory Agency to study TSHA-102 in pediatric patients in mid-2023 and file an investigational new drug application with the FDA in the second half of 2023.