Taysha Gene Therapies, Inc.

Greetings, and welcome to the Tatia Gene Therapy's first quarter 2025 earnings call. At this time, all participants are in listen-only mode. The question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star then zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Haley Collins, Director, Head of Corporate Communications. Please go ahead.

Thank you. Good morning and welcome to Tayshia's first quarter 2025 financial results and corporate update conference call. Earlier today, Tayshia issued a press release announcing financial results for the first quarter ended March 31st, 2025. A copy of this press release is available on the company's website and through our SEC filing. Joining me on today's call are Sean Nolan, Cassius Chief Executive Officer, Sigmar 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. Please note that on today's call, we will be making forward-looking statements 102, including the reproducibility and durability of any favorable results initially seen in the patient's dose to date in clinical trials 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 additional trials and reporting data from our clinical trials, advice from the FDA on the regulatory pathway for TASHA 102, the potential for the product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, the market opportunity for our programs, and our current cash resources supporting our planned operating expenses and capital requirements into the fourth quarter of 2026. This call may also contain forward-looking statements relating to TASIA'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 TASHA's actual results to differ materially from those stated or implied in such forward-looking statements. on certainties that we face, please see the reports that we have filed with the Securities and Exchange Commission, including in our annual report on Form 10-K for the full year and the December 31, 2024 that we filed on February 26, 2025, and our quarterly report on Form 10-Q for the quarter ended March 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, May 15, 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 Nolan.

Thank you, Haley, and welcome, everyone, to our first quarter 2025 financial results and corporate update conference call. I will begin with a brief update on our recent activities. then Sukha Nagendran, president and the head of R&D of Tayshia, will provide an update on our lead Tayshia 102 gene therapy program and clinical development for Rett syndrome. Cameron Alam, our chief financial officer, will follow up with a financial update. And I will provide closing remarks and open up the call for questions. This year has been marked by strong execution across our Tayshia 102 program and clinical evaluation for pediatric, adolescent, and adult patients suffering from Rett syndrome. We are pleased with the significant regulatory and clinical progress that we believe continue to support a clear path to registration. Importantly, our analysis of the natural history data, coupled with the longer-term clinical data from our low-dose cohort and interim high-dose data that we have collected across a broad range of ages and stages of patients, with Rett syndrome in our two Reveal Phase 1-2 trials have further informed the therapeutic potential of TASHA-102 and supported our alignment with the US FDA on key elements of our development plan for Part B, the pivotal phase of our trials. In February, we shared that we completed dosing of the 10 patients in Part A. the dose escalation portion of the Reveal Phase 1-2 adolescent-adult trial and the Reveal Phase 1-2 pediatric trial, with six patients in Cohort 2 evaluating the high dose of TASHA-102 of 1e to the 15th total vector genomes, and four patients in Cohort 1 evaluating the low dose of TASHA-102 of 5.7e to the 14th total vector genomes. As our data shows, further mature, we're pleased that TASHA-102 continues to be generally well-tolerated across the high- and low-dose cohorts with no treatment-related serious adverse events or dose-limiting toxicities as of the April 10, 2025 data cut-off. Recall, patients being evaluated in our REVEAL Phase 1-2 trials are in the post-regression period of the disease. where functional gains or restoration of loss function are not expected to occur in the untreated population. Previously, we shared clinical data from the low-dose cohort in our reveal trials, where pediatric and adult patients with advanced disease not only showed clinical improvements, but also gained functional skills across the domains of fine motor, gross motor, and socialization and communication which represent improvements in activities of daily living. This included beginning to use eating utensils, sitting independently, standing up from a chair independently, and the ability to use an eye gaze communication device. Each of these functional gains reflect meaningful skills that can significantly improve a patient's quality of life by affording greater independence and autonomy. These functional gains, which are not expected to occur in the untreated population of patients with Rett syndrome based on natural history data and the additional clinical data we have collected since from our reveal trials, have supported our interactions with the FDA regarding the optimal regulatory pathway for TASHA-102. Over the past 18 months, we have maintained frequent ongoing discussions with a broad FDA review team, including senior leadership through the regenerative medicine, advanced therapy, or RMAT mechanism. These discussions, which have been rooted in robust data-driven findings, have been aimed at advancing TASHA 102 toward a pivotal trial design in which clinically meaningful functional gains are assessed in a rigorous and bias-mitigated manner across a broad patient population. To date, we believe our interactions with the FDA have consistently been productive and supportive of our development approach. As such, I'm pleased to share that we have obtained written alignment from the FDA on key elements of our pivotal Part B trial design for TASHA-102 and next steps to enable the initiation of the pivotal trial. Importantly, The FDA advised us to proceed directly to submitting our pivotal trial protocol and associated statistical analysis plan as an amendment to the investigation on new drug or IND application, which we expect to submit in the current quarter. This approach eliminates the need for a formal end of phase meeting, which may expedite study initiation and registration. We truly appreciate the clear, constructive, and collaborative interactions with FDA to date and believe this progress on our registrational pathways support the strength of our data-driven approach and further enables our goal to bring TASHA-102 to patients with this devastating disease as expeditiously as possible. We are focused on finalizing the details of our protocol and statistical analysis plan as we prepare to submit the IND amendment this quarter. In the coming weeks, we plan to provide a fulsome update on our pivotal Part B trial design, our Rett Syndrome natural history data analysis, and the clinical data from Part A of our reveal trials as part of a TASHA 102 program update in conjunction with the International Rett Syndrome Foundation's 2025 Rett Syndrome Scientific Meeting taking place June 9th through the 11th. At the IRSF meeting, we will deliver three oral presentations related to Tayshia-102, including one focused on our clinical data. As we approach these critical milestones, our confidence in our differentiated gene therapy candidate continues to strengthen based on the recent developments highlighted today. We believe Tayshia-102 has the potential to provide meaningful benefit to a broad population of patients with Rett syndrome using a minimally invasive delivery approach with a clear path to registration based on the critical alignment reached with FDA. I will now turn the call over to Sukhu to provide more context on these advancements that further support a clear path to registration. Sukhu.