The company is focused on developing and commercializing adeno-associated virus (AAV)-based gene therapies, including TSHA-118, to treat monogenic diseases of the central nervous system in both rare and large patient populations.

TSHA-118 is a self-complementary AAV9 gene replacement therapy designed to express a human codon-optimized CLN1 transgene. The global trial is a single-arm, open-label, phase I/II trial evaluating TSHA-118 for the treatment of CLN1 disease using commercial-grade material. Preliminary clinical safety and PPT1 enzyme activity data in the serum and cerebrospinal fluid (which correlates with disease severity) are expected in the first half of 2022.

There is an open investigational new drug application in the U.S. for TSHA-118 in CLN1 disease. TSHA-118 has been granted an orphan drug designation, a rare pediatric disease designation, and a fast-track designation from the U.S. Food and Drug Administration, as well as an orphan drug designation from the European Commission to treat CLN1 disease.

Preclinical data have demonstrated that intrathecal treatment with TSHA-118 significantly extended survival of CLN1 knockout mice and improved behavior, according to Taysha.

TSHA-118-treated mice showed persistent supraphysiological levels of active PPT1 and sustained preservation of motor function. In CLN1 knockout mice, TSHA-118 was safe and well-tolerated with no associated adverse events, suggesting a wide therapeutic window for clinical dosing, the company said.