By Connor Lynch

Pictured: FDA sign in its headquarters/iStock, Grandbrothers
Taysha Gene Therapies has decided to drop its lead experimental AAV-based gene therapy candidate after the FDA reiterated calls for the company to put the treatment through a randomized, double-blind placebo-controlled trial.
The Dallas-based company announced on Tuesday that it would no longer be developing its TSHA-120 treatment for giant axonal neuropathy (GAN) based on the FDA’s Type C meeting feedback regarding the therapy’s potential pathway.
“FDA continues to recommend a randomized, double-blind, placebo-controlled trial as the optimal path to demonstrate efficacy in TSHA-120,” the company said in a statement.
Taysha noted in the announcement that the FDA “provided a potential path for a single-arm trial with an external control group matched with to-be treated patients by multiple prognostic factors and recommended longer term follow up to account for potential bias.”
CEO Sean Nolan said in a statement that the company plans “to pursue external strategic options for TSHA-120 that may enable further development of TSHA-120 and help patients with this devastating disease.”
GAN is an ultra-rare autosomal recessive disease of the central and peripheral nervous systems characterized by numbness and muscle weakness, which progress to seizures, loss of control over the body and gradual mental decline.
The company initially submitted Phase I/II data for the FDA’s review in 2022, with the agency coming back noting the need “to address the heterogeneity of disease progression in GAN and the effort-dependent nature of MFM32 as a primary endpoint in an unblinded study.”
Taysha followed up with a new comprehensive analysis that it presented in June 2023, with the FDA ultimately reiterating its previous feedback.
Meanwhile, Taysha is shifting gears after having to significantly trim its development pipeline since its initial public offering in September 2020, having gone from listing 18 programs in development across its portfolio down to just one—with another three including TSHA-120 available for external strategic deals. The remaining candidate, TSHA-102, is a potential treatment for Rett syndrome, a rare genetic neurological and developmental disorder.
“This strategic program prioritization is expected to extend our cash runway into the fourth quarter of 2025 to support the continued clinical development of TSHA-102 in Rett syndrome,” Nolan said. “We remain focused on continuing to evaluate the therapeutic potential of TSHA-102 in our ongoing REVEAL Phase 1/2 trial in adults and our planned pediatric trial.”
Tuesday’s announcement also noted that Astellas will not be exercising its option to obtain an exclusive license to the therapy. In October 2022, Astellas bought 15% of Taysha’s outstanding common stock for $50 million with the exclusive option to license TSHA-120 and TSHA-102.
“While Astellas has declined to exercise its option for the GAN program, we remain focused on the needs of patients impacted by devastating diseases and look forward to continuing our relationship with Taysha,” Richard Wilson, Astellas’ senior vice president and primary focus lead of genetic regulation, said in a statement.