Taysha ends work on gene therapy as Astellas walks away, FDA requests randomized trial

Astellas has turned down the chance to option an asset from Taysha Gene Therapies. And, with Taysha identifying study design feasibility challenges after talking with the FDA, the biotech has stopped internal development of the candidate and added it to a large pile of dropped and deprioritized programs. 

Taysha gave Astellas an option to license its gene therapy candidate TSHA-120 in the neurodegenerative disorder giant axonal neuropathy (GAN) 11 months ago as part of a two-asset agreement. Astellas paid $20 million upfront and invested $30 million in Taysha to secure the two options and agreed to make a decision on the GAN program after seeing the minutes of the end-of-phase 2 meeting with the FDA.

As has happened with several of Astellas’ gene therapy bets, the situation went downhill quickly from then on. The FDA emphasized the need to address the heterogeneity of disease progression in GAN and voiced a concern about the primary endpoint at the meeting, leading Taysha to submit a new analysis.

The new analysis failed to change the FDA’s thinking. After a second meeting, the agency continues to recommend a randomized, double-blind, placebo-controlled trial as “the optimal path” to showing the efficacy of TSHA-120, according to Taysha. The FDA suggested a single-arm trial with an external control group matched with to-be-treated patients with longer-term follow-up as another potential path.

None of the routes to market appealed to Taysha. Citing study design feasibility challenges, the biotech is stopping the development of TSHA-120 in GAN and seeking external strategic options for the program. If Taysha is to find a partner, it will need to identify a company willing to work through challenges that led both it and Astellas to drop the asset. 

The discontinuation of TSHA-120 continues the rapid reduction of Taysha’s once-sprawling pipeline. At the time of its IPO in September 2020, the biotech listed 18 programs across its portfolio. Most of the assets were in the discovery stage, and some targeted undisclosed indications, but the pipeline spoke to the ambition of the newly public biotech.

Today, Taysha’s publicly disclosed pipeline features one priority candidate, the Rett syndrome prospect TSHA-102, and three, including TSHA-120, that are now deprioritized and available for external strategic deals. Stopping development of TSHA-120 extends Taysha’s cash runway into the fourth quarter of 2025, up from the third quarter under the prior plan, and positions it to generate data on TSHA-102 in Rett.