Taysha Gene Therapies, Inc.

Good day, and thank you for standing by. Welcome to the Tayshia Jean Therapy's full-year 2025 Financial Results Conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Haley Collins, Senior Director of Corporate Communications and Investor Relations. Please go ahead.

Thank you. Good morning and welcome to Tayshia's full year 2025 financial results and corporate update conference call. Earlier today, Tayshia issued a press release announcing financial results for the full year ended December 31st, 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, Tayshia's Chief Executive Officer, Sukumar Nagandran, President and Head of R&D, and Cameron Alam, 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 Tayshia-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 and making regulatory communications with the FDA on the regulatory pathway for Tayshia-102, the potential for the product candidate to receive regulatory approval from the FDA, or equivalent foreign regulatory agencies, our ability to realize the benefits of breakthrough therapy designation for TASHA 102, our ability to drive long-term value for stockholders, and the market opportunity for our programs. This call may also contain forward-looking statements relating to TASHA's growth, forecast 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 TASHA's 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 we have filed with the SEC, including in our annual report on Form 10-K for the full year, December 31, 2025, that we filed today. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, March 19, 2026. Tayshia 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 Nolan.

Thank you, Haley. Welcome to our full year 2025 financial results and corporate update conference call. On today's call, I will begin with a brief update on our recent clinical, regulatory, and commercial readiness activities. Then, Dr. Sukhandran, our president and head of R&D, will provide a clinical update on the TASHA 102 program. Cameron Alam, our chief financial officer, will follow up with a financial update, and I will provide closing remarks and then open the call up for questions. 2025 was a year of significant execution for TASHA. We announced compelling Reveal Phase 1-2 data across pediatric, adolescent, and adult patients with Rett syndrome treated with TASHA-102, received FDA breakthrough therapy designation for TASHA-102, and secured written FDA alignment on our Reveal Pivotal and Aspire trial designs, paving the way for a potentially streamlined path toward BLA submission. This progress has set the stage for what we expect to be a transformative year ahead for TACIA as we focus on completing the pivotal development of TACIA 102 and bolstering our commercial readiness efforts as we advance towards potential registration. We've maintained ongoing, constructive dialogue with the FDA over the past two years, which has enabled alignment on a pathway that we believe reflects the rigorous, systematic data collection and well-controlled study design and endpoint selection required by the FDA for a robust data-driven application. In 2025, we finalized alignment with the FDA on our Reveal Pivotal Trial Protocol and Statistical Analysis Plan in support of our Plan BLA submission. And we were pleased to initiate the pivotal trial in the fourth quarter of 2025 with the dosing of our first patient. Multiple patients have now been dosed in the trial, with enrollment advancing across multiple sites. We remain on track to complete dosing in the second quarter of 2026. Importantly, both high- and low-dose TASIA-102 continues to be generally well-tolerated, with no treatment-related serious adverse events or dose-limiting toxicities observed in the patients treated in both the Reveal Phase 1-2 and Reveal Pivotal Trial as of the March 2026 data cutoff. In addition to initiating our Reveal Pivotal trial, we recently received FDA clearance to initiate the safety-focused ASPIRE trial, following written FDA alignment on the ASPIRE trial design and data for inclusion in our BLA submission to support a broad label for TASHA-102 for patients aged two years and older with Rett syndrome. ASPIRE will enroll three females with Rett syndrome, aged two to less than four years. evaluating the safety and preliminary efficacy of a single intrathecal administration of the high dose of TASHA-102, 1D to the 15 total vector genomes, scaled to account for the lower brain volume in the 2 to less than 4-year-olds. The written alignment we reached with the FDA outlines that our planned PLA submission will include a minimum of three months of Aspire safety data in the two to less than six-year-olds population will be extrapolated from the data collected in the Revealed Pivotal Trial to support the broad label. We are on track to complete dosing for Aspire in the second quarter of 2026. We believe this recent FDA alignment on Aspire, together with the alignment on a six-month interim analysis for a Revealed Pivotal Trial, potentially streamlines our path toward BLA submissions for TASHA-102. In the first quarter of 2026, we attended a Type C meeting with the FDA and reached written alignment on the CMC requirements for our Plan BLA submission. Specifically, we further aligned with FDA on our proposed comparability approach between Tatia 102 material derived from the clinical and final commercial manufacturing processes. The FDA agreed that the approach may support pooling data and the ASPIRE trial for the planned VLA submission. Importantly, we believe this creates flexibility and will further strengthen the overall data set for the VLA package by including longer-term data and enabling a comprehensive assessment of safety and efficacy data that's been generated across the entire development program. Additionally, the FDA endorsed our proposed Process Performance Qualification, or PPQ, campaign strategy to support process validation for the BLA submission. This included the stability data package, the potency assay strategy, and the execution of BLA-enabling PPQ lots using the commercial manufacturing process, which we expect to initiate in the second quarter of 2026. This feedback aligns with the agency's January 2026 guidance aimed at increasing flexibility on requirements for cell and gene therapies to advance innovation. With this alignment, we are confident that our CMC activities are on track to support our planned VLA submission in step with the pivotal data set readout. We truly appreciate the consistent, constructive, and collaborative interaction we have held with the FDA to date and believe our regulatory progress highlights the strength of our data-driven approach and further supports our goal to bring TASHA 102 to patients with Rett syndrome as safely and expeditiously as possible. We will continue to engage with the FDA as we prepare for our planned BLA submission. In addition to our clinical and regulatory progress, we continue to bolster our commercial readiness activities. As a reminder, Rett syndrome is a devastating, rare, and progressive neurodevelopmental disease with high unmet need and a profound lifelong burden for patients and caregivers. It is well characterized clinically defined by impairments across multiple clinical domains, including fine gross motor function, communication, autonomic function, and seizures. While Rett syndrome is a heterogeneous condition that presents with different levels of clinical severity based on each patient's distinct genetic background, natural history data show that patients follow a common trajectory regarding the achievement of functional developmental skills, with the likelihood of spontaneous gain or regain of developmental milestones falling to approximately zero after six years of age. The multi-domain impairments result in loss of independence, with most individuals requiring 24-7 care and lifelong support for daily activities, such as eating or sitting up, severely impacting quality of life for patients and caregivers. This burden and the limitations of currently approved therapies the underlying genetic root cause, have created a strong urgency for new treatment options capable of delivering functional improvements. We believe this urgency, combined with the estimated 15,000 to 20,000 patients with Rett syndrome across the U.S., EU, and U.K., underscores the substantial market opportunity for TASHA-102. Within the U.S. specifically, Patient estimates range from 6,000 to 9,000 patients based on claims data and epidemiology data. Because Rett syndrome is a neurodevelopmental condition, and based on the Phase I-II data we've reported to date across pediatric, adolescent, and adult patients, we believe that most patients with Rett syndrome can meaningfully benefit from treatment. TASHA-102 is uniquely designed to address the root cause of Rett syndrome and, as such, has the potential to meaningfully alter the natural history of disease and offer patients the opportunity to achieve functional milestones that would otherwise not be possible according to natural history. Recently completed market research reinforces this opportunity as it demonstrated high anticipated demand from both clinical The research findings are compelling for two main reasons. First, the research suggests that clinicians anticipate broad adoption of TASHA-102 across pediatric, adolescent, and adult patients with Rett syndrome. Caregivers similarly indicated that they would actively pursue and improve gene therapy with a target product profile consistent with TASHA-102. Caregivers emphasized that improvements in existing function or the achievement of new functional gains would be meaningful for individuals with Rett syndrome as they translate into greater independence in daily living, such as speaking in phrases, walking with support, or finger-feeding, which we have observed in patients treated with TASHA-102 and Reveal Part A. Second, clinical outcomes will be the ultimate driver. However, market research indicated that brain CNS delivery, citing its familiarity, accessibility, and scalability, enabling the potential to safely and efficiently treat patients across institutions, from large centers of excellence to regional and local institutions. This facilitates broad patient access. Specifically, intrathecal administration as it is used to deliver TASHA 102, is a routine, minimally invasive delivery approach that does not require a surgical suite or delivery by a neurosurgery expert. This enables the potential for TASHA 102 to be delivered as an outpatient procedure, which in turn may immediately expand the treatment footprint, given the administration in the commercial setting will not be limited only to centers of excellence. We believe this broader footprint would enable us to reach patients where they are already receiving care and support, and this is a scalable adoption as demand grows. Finally, as we advance towards registration, we are continuing to build out our internal commercial infrastructure. To that end, we recently appointed Brad Martin as Senior Vice President of Market Access and Value, further strengthening our commercial leadership team. Brad brings over two decades of leadership experience in market access and commercial strategy. pre-commercial, and product launch planning, as well as payer and health system engagement within the gene therapy space. He previously held senior roles at Neurotech Pharmaceuticals, Sarepta Therapeutics, and Avexis. At Avexis, he played a crucial role in securing market access for the blockbuster gene therapy Zolgensma for the treatment of spinal muscular atrophy. We plan to continue to build out that commercial capability to prepare for a potential commercialization, and we expect to share additional details on our TASHA 102 commercial strategy in the second half of the year. I would now like to turn the call over to Sukhu to discuss progress on the clinical front in more detail. Sukhu?