Taysha Gene Therapies, Inc.

Good day, everyone, and welcome to the Tayshia Gene Therapy's third quarter 2025 earnings call. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question and answer session. You may register to ask a question at any time by pressing the star and 1 on your telephone keypad. You may withdraw yourself from the queue by pressing star and 2. Please note, this call may be recorded, and I will be standing by if you should need any assistance. It is now my pleasure to turn the conference over to Haley Collins. Please go ahead.

Thank you. Good morning and welcome to our third quarter 2025 financial results and corporate update call. Earlier today, Tayshia issued a press release announcing financial results for the third quarter ended September 30th, 2025. A copy of this press release is available on the company's website and through our SEC filings. Joining me on today's call are Sean Nolan, TASHA's Chief Executive Officer, Sukumar Nagandran, President and Head of R&D, and Kamra Lam, Chief Financial Officer. We will hold a question and answer session following our prepared remarks. On today's call, we will be making forward-looking statements, including statements concerning the potential of TASHA-102, including the reproducibility and durability of any favorable results initially seen in patients' dose-to-date and clinical trials, including with respect to functional milestones to positively impact quality of life and alter the course of disease in the patients we seek to treat, our research, development, and regulatory plans for our product candidates, including the timing of initiating additional trials, reporting data from our clinical trials and making regulatory submissions, timing our outcomes of communications with the FDA on the regulatory pathway for TASHA-102, the potential for the product candidate to receive regulatory approval from the FDA or equivalent regulatory agencies, our ability to realize the benefits of breakthrough therapy designation for TASHA-102, and the market opportunity for our programs. This call may also contain forward-looking statements relating to TASHA's growth, forecasted cash runway and future operating results, discovery and development of product candidates, strategic alliances and intellectual property, as well as matters that are not historical facts or information. Various risks may cause cautious actual results to differ materially from those stated or implied in such forward-looking statements. For a list and description of the risks and uncertainties that we face, please see the reports that we had filed with the SEC, including in our annual report on Form 10-K for the full year, December 31st, 2024, that we filed February 26th, 2025. In our quarterly report on Form 10-Q, the quarter ended September 30, 2025, that we filed today. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, November 4, 2025. Taysha undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable securities laws. With that, I would now like to turn the call over to our CEO, Sean Mullen.

Thank you, Haley, and welcome everyone to our third quarter conference call. I will begin with an update of our recent corporate activities and progress across our TASHA 102 Rett Syndrome program. Sukhu will then discuss the new supplemental analysis from Part A of our Reveal Phase 1-2 trials. Cameron will follow up with a financial update, and I will provide closing remarks before opening the call to questions. In the quarter, we believe we made meaningful progress that sets the stage for what could be a transformative period ahead for Tayshia. The recent regulatory clarity and progress we've achieved, which was enabled by the strength of our REVEAL Part A data set, rigorous data evaluation methodology, and our natural history data analysis, allows us to focus on executing our REVEAL pivotal trial and advancing towards BLA submission with clarity and confidence. A major milestone was the receipt of FDA breakthrough therapy designation for TASHA-102 at the end of September. This designation is designed to expedite the development and review of therapies for serious conditions that have demonstrated preliminary clinical evidence of substantial improvement over available treatments in one or more clinically meaningful endpoints. TASHA-102 received breakthrough therapy designation based on the FDA's review of available safety and efficacy data from all 12 pediatric, adolescent, and adult patients treated with TASHA-102 in Part A of our Reveal Phase 1-2 trials, including clinical data from the previously disclosed May 2025 data cutoff. Receiving breakthrough designation highlights the FDA's recognition of both the significant unmet medical need among the estimated 10,000 patients suffering from Rett syndrome in the U.S. and the therapeutic potential of TASHA-102 to redefine the treatment paradigm for this devastating disease. Notably, over 80% of programs with breakthrough therapy designation that proceeded to file for approval have ultimately received FDA approval. We look forward to continued engagement with the FDA as we advance toward potential registration. In September, we finalized alignment with FDA on our Revealed Pivotal Trial Protocol and Statistical Analysis Plan in support of our Plan BLA submission for TASHA 102, following resolution of remaining clinical and statistical queries. Importantly, Our previously aligned upon key design elements remain unchanged. In line with FDA's guidance for cell and gene therapy programs that was issued in September, we believe that by prospectively aligning with FDA on the statistical analysis plan for our pivotal trial helps ensure that the data set collected will be considered reliable and suitable for BLA submission. We are enrolling 15 patients in the developmental plateau population of Rett syndrome with a primary endpoint of response rate, which is defined as the percentage of patients who gain or regain one or more of the 28 natural history-defined developmental milestones. A response rate of 33%, equivalent to 5 out of 15 patients, is the minimum threshold for success sufficient to achieve our primary endpoint. Notably, we've observed a 100% response rate across the 10 patients in Part A of our revealed trials. Additionally, we align with the FDA on a six-month interim analysis that may serve as the basis for BLA submission, potentially accelerating our planned BLA submission by at least two quarters. As previously disclosed, the data from Part A of the REVEAL trials demonstrated an 83% response rate at six months post-treatment, with five of the six patients treated with the high-dose TASHA-102 achieving a developmental milestone. We observed a consistent pattern of sustained milestone gains with a deepening of effect or additional milestone gains over time. By nine months post-treatment, the data demonstrated a 100% response rate across the six treated high-dose patients in Part A. We believe these data support both the suitability of the six-month time point to demonstrate clinically meaningful efficacy and that the six-month efficacy data may be representative of treatment effects at 12 months. We believe this enabled our alignment with FDA that a six-month interim analysis may serve as the basis for BLA submission. It's important to understand that we believe we received breakthrough therapy designation and achieved FDA alignment largely due to the results of the rigorous clinical evaluation methodology applied to our video evidence developmental milestone data from Part A of the Reveal Phase 1-2 trials. In Part A, videos were centrally rated by multiple independent reviewers using milestone definitions from the Pivotal Trial Protocol to ensure an objective, consistent evaluation of milestone gain and regain in the developmental plateau population, where these gains are not expected to spontaneously occur. By adhering to rigorous milestone evaluation criteria based on natural history, this approach minimizes bias and avoids overcounting milestones by ensuring the milestones are truly eligible for gain or regain. As a result, this provides a reliable reflection of TASHA 102's disease-modifying therapeutic effect and ensures that the pivotal trial is well-powered to demonstrate efficacy. We will continue to have frequent and consistent interactions with the FDA. We presented our revealed Part A data from the May 2025 data cutoff, including the new supplemental analysis which provides supportive evidence that further reinforced TASHA 102's consistent multi-domain impact on activities of daily living at the Child Neurology Society Annual Meeting in October. Sukhu will discuss these results shortly. With the strength of our Part A clinical data and a clear FDA-aligned path to potential registration, We believe we are strongly positioned to initiate our Revealed Pivotal Trial and accelerate execution towards BLA submission. Dosing of the first patient in our Revealed Pivotal Trial is scheduled and on track for this quarter, with additional patient enrollment expected to continue across multiple sites this quarter. On the heels of our strong clinical and regulatory progress, we are thrilled to have regained full global rights to our TASHA 102 Rett Syndrome programs. We regained these rights in October following the expiration of our 2022 option agreement with Astellas, which had granted Astellas an exclusive option to enter into a negotiation period to license Tayshia 102 and certain rights with respect to change and control transactions. We appreciate the collaborative relationship we've had with Astellas and the unencumbered rights to Tayshia 102 that we now hold enable us to focus on driving long-term value with full strategic flexibility and optionality. We continue to build out our infrastructure to support Advancing Tayshia 102 toward late-stage development and potential commercialization, if approved. This September, we strengthened our commercial leadership team with the appointment of David McNinch as Tayshia's Chief Commercial Officer. David brings over two decades of experience in global commercialization and strategic market development across multiple therapeutic areas. Most recently, he served as chief business officer at Encoded Therapeutics, where he led the commercial and partnering strategy across the company gene therapy portfolio. He previously held senior commercial roles at Prothena as well as Intramune, where he led the launch of Espriot. the first FDA-approved treatment for idiopathic pulmonary fibrosis, and supported the company's acquisition by Roche. David reports to Sean McAuliffe, TASHA's chief business officer. Previously at Avexis, Sean led the development and execution of the commercial launch of Zolgensma for spinal muscular atrophy, the first FDA-approved gene therapy for the treatment of a monogenic CNS disease, which has reached blockbuster status. With an estimated 15,000 to 20,000 patients with Rett syndrome across the US, EU, and UK, compelling clinical data from Part A of our REVEAL trials, and a minimally invasive, commercially advantageous delivery approach, we see a significant opportunity to address a profound unmet medical need and drive long-term value. We believe our strong balance sheet, team with proven gene therapy experience, and the clear path to registration strongly position us to initiate a Reveal Pivotal Trial and accelerate execution toward BLA submission. I will now turn the call over to Sukhu to discuss our clinical progress in more detail. Sukhu?