Taysha Gene Therapies, Inc. Q3 FY2025 earnings call

• Received FDA Breakthrough Therapy designation for TSHA-102 in September, recognizing the significant unmet medical need in Rett syndrome and therapeutic potential of TSHA-102.
• Made progress in REVEAL Phase I/II trials, with 100% response rate in Part A across 10 patients, and new supplemental analysis showing additional skill gains outside the 28 natural history-defined milestones.
• Regained full global rights to the TSHA-102 Rett syndrome program in October following the expiration of the option agreement with Astellas.
• Appointed David McNinch as Chief Commercial Officer to build out commercial leadership team for potential commercialization.
• Scheduled dosing of the first patient in the REVEAL pivotal trial this quarter, with additional enrollment expected across multiple sites.

Taysha primarily focuses on the TSHA-102 Rett syndrome program. No distinct product segments with multiple financial performances to report.

• Expect to dose the first patient in the REVEAL pivotal trial this quarter with additional enrollment at multiple sites.
• Plan to report longer-term clinical data from Part A of the REVEAL Phase I/II trials in the first half of 2026.
• Confident in alignment with FDA on the statistical analysis plan and clinical protocol for the pivotal trial, with goal of accelerating BLA submission.

• Various risks may cause actual results to differ materially from forward-looking statements, as detailed in SEC filings including annual report on Form 10-K and quarterly report on Form 10-Q.

Q: Just curious, this time around in the pivotal trial, you have a lot more evidence going for you. So can you talk about the pipeline of interest and demand for being in this trial and then your thoughts about how long it could take to fully enroll?

A: Sean Nolan and Sukumar Nagendran responded, stating high demand to be in the trial due to safety and efficacy data, multiple sites identified, with potential enrollment of 15 patients in 3-6 months.

Q: I was just wondering if you could touch on expectations for the longer-term data in the first half of next year and also help us understand in the context of your discussions with the FDA what they have signed off on in terms of that minimum threshold for success here that's sufficient for filing.

A: Sean Nolan responded, discussing plans to provide updates on safety and efficacy data in first half of 2026, and detailed alignment with FDA on statistical analysis plan and protocol with threshold of 33% response rate as sufficient for filing.

Q: I wanted to get a little bit more color on how you're thinking about the way we should all be thinking about the data from the younger patients, meaning the 2- to 6-year-olds, relative to the 6-plus-year-olds as it relates to efficacy in particular. And then on safety, should we be expecting to see a staggered release of safety data on that younger population relative to the older population? Basically, when could we expect to see data start to come in from that cohort base?

A: Sean Nolan responded, stating goal to include younger patients in BLA submission, safety-focused study for younger patients with plan to dose them mid-2026 and extrapolate efficacy from 6-plus population.

Q: So maybe just another one on protocols here. How much leeway do you think the agency provides regarding the method of video review and is it fair to assume that all companies in the space receive the same guidance on that?

A: Sean Nolan responded, stating FDA focused on rigor of data collection for primary endpoint, Taysha ran pilot with multiple central raters to bolster case, and FDA expects high fidelity and inter-rater reliability in video review.

Q: Are there any updates on your plans in Europe or discussions with the EMA on the applicability of Part B? And separately, is the bar for the interim analysis similar to that for the final 12-month analysis?

A: Sean Nolan responded, stating focus on U.S. market initially but planning to engage with Europe, and bar for interim analysis tied to statistical plan and aligned with FDA.

Q: Congrats on the progress. Wondering if you'd tell us anything additional about timelines for IRB approval for the additional 2 to 5 sites that you'll need for the pivotal. And just when thinking about enrollment for this study, is there anything more you could say about number of patients you could potentially have enrolled by end of this year? Just helping provide some line of sight to potentially getting to data from the pivotal by the end of next year.

A: Sean Nolan responded, stating need for IRB approval for new protocol, and anticipation of less than 15 patients in younger patient study with plans to provide more info in Q1 2026.

Q: Just a couple of commercial questions here maybe. So you're starting the commercial buildout now with the hiring of a Chief Commercial Officer. Maybe talk about the footprint you'll need, how it will look, and maybe the milestones that we should expect in terms of, I guess, access progress. And then maybe a related question. Of the 28 developmental milestones, are there any that you think matter more, be it communication, fine motor, or gross motor milestones in terms of clinical acceptance among the physician community, or in terms of ease of access that we should be thinking about?

A: Sean Nolan responded, discussing commercial buildout with David McNinch, importance of all 28 milestones, and strong commercial team with experience in gene therapy launches.

Q: Wanted to dig into the statistical plan a little bit. Thanks for all the color so far on the call regarding alignment and the FDA. Given that the trial design is novel and there is not an external control arm, per se, wonder how the p-value is derived. And also in terms of the interim analysis, how unambiguous or subjective the threshold is for triggering filing based on interim? In other words, do you run any risk if you file on interim? Just wondering with regard to the actual data and the p-value in making that decision.

A: Sukumar Nagendran responded, explaining objective evaluation of milestones, 6-month interim analysis tied to statistical plan with minimal impact on p-value, and clear definition of milestone gain and regain.

Q: The question is, I just wanted to ask you to please remind us what is the actual definition of regaining again. And assuming that at the 6-month interim data is positive, how soon you can start filing for BLA?

A: Sukumar Nagendran responded, defining regain as a lost milestone being regained and gain as a new milestone achieved, with clear examples, and plan to file for BLA based on aligned statistical plan and data.