Taysha Gene Therapies, Inc.

Ladies and gentlemen, good morning and welcome to Taysha Jean Therapy's second quarter 2025 earnings conference call. At this time, all participants are in listen-only mode. A brief question and answer session will follow the formal presentation. If anyone requires operator assistance during the conference, please signal the operator by pressing star and zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Haley Collins, Director, Head of Corporate Communications. Please go ahead.

Thank you. Good morning and welcome to our second quarter 2025 financial results and corporate update conference call. Earlier today, Tayshia issued a press release announcing financial results for the second quarter ended June 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, Tayshia's Chief Executive Officer, Dukumar Nagandran, President and Head of R&D, Cameron Alam, Chief Financial Officer, and Dr. Elsa Rosignol, Director of the Integrated Rett Syndrome Clinic at St. Justine in Montreal and Principal Investigator of the Reveal Phase 1-2 Trials. We will be presenting slides to accompany our prepared remarks today, which will be available on our website after the call. We will host a question and answer session following our prepared remarks. Please note that Dr. Rosignol will be available to take questions until 9.20 a.m. Eastern Time, after which she will be stepping away for her clinic commitments. 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 in clinical trials, including with respect to functional milestones, and to our other product candidates 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 or outcomes of communications with the FDA and Health Canada on the regulatory pathway for TASHA-102, the potential for product candidates, to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and a market opportunity for our programs. This call may also contain forward-looking statements relating to Tayshia'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 Tayshia'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 we face, please see the reports we filed with the SEC, including in our annual report on Form 10-K for the full year ended December 31st, 2024, we filed February 26th, 2025. In our quarterly report on Form 10-Q for the quarter ended June 30th, 2025, we filed today. This conference call contains time-sensitive information that's accurate only as of the date of this live broadcast, August 12th, 2025. Tayshia undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this 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 second quarter conference call. I will begin with an update on our recent activities and regulatory progress for our lead TASHA 102 Rett Syndrome Program, including new details of our FDA-aligned pivotal trial design and our registrational pathway. Next, Suku will discuss our natural history data analysis, which underpins our reveal pivotal trial designs. I've invited Dr. Elsa Rosenahl, Director of the Integrated Rett Syndrome Clinic at St. Justine in Montreal, and a principal investigator of the REVEAL trials, to present the previously disclosed Part A clinical data from our REVEAL Phase 1-2 trials that she presented at the International Rett Syndrome Foundation Scientific Meeting in June. Those who attended may recall how impactful her presentation was to the audience. Today we're excited to expand its reach to the broader community as these data have been central to our clinical discussions with regulators in preparation for our pivotal trial. Cameron will then follow up with a financial update and I will provide closing remarks before opening the call to questions. We have continued to make strong progress supporting the advancement of our TASHA 102 program. This included obtaining alignment with the FDA and Health Canada to proceed with initiating our Reveal Pivotal Trial, reporting positive clinical data supporting the therapeutic potential of TASHA-102, and strengthening our balance sheet. We believe this meaningful progress sets us on a clear and efficient path towards the potential registration of TASHA-102. In May, we announced that we had reached alignment with FDA on key design elements of our Reveal Pivotal Trial and next steps for enabling study initiation. Subsequently, we submitted our IND application amendment to the FDA and CTA amendment to Health Canada. I am now pleased to report that we have officially commenced site activation for our Reveal Pivotal Trial. In accordance with the key design elements we previously previously aligned on with FDA following receipt of no objection letter from Health Canada and feedback from the FDA. As a result of this progress, we anticipate beginning patient enrollment for our pivotal trial in the fourth quarter of this year. Our frequent and constructive dialogue with the FDA through the RMAT mechanism has been instrumental in enabling us to navigate this novel regulatory pathway, which I will discuss in more detail shortly. Rett syndrome is a rare, progressive, and debilitating neurodevelopmental disease affecting an estimated 15,000 to 20,000 patients across the US, Europe, and UK. It often necessitates 24-7 care and lifelong support. Despite the severity, there are no currently approved therapies that treat the underlying genetic root cause of this disease, underscoring the urgency for new therapeutic advancements. TASHA-102 is a highly differentiated gene therapy candidate designed to target the genetic root cause of Rett syndrome. With key attributes that intend to support safety and potential commercial viability, we believe TASHA-102 is poised to redefine the treatment landscape for Rett syndrome. Specifically, it leverages the clinically and commercially proven AAV9 vector which is a well-characterized safety profile that's been demonstrated in studies for other third-party gene therapies across multiple indications. Another important distinction is that TASHA-102 is administered via lumbar intrathecal injection, which is a routine, minimally invasive delivery approach. Commercially, this can be advantageous in that it does not require a surgical suite or neurosurgery expert delivery. and it can be performed as a routine outpatient procedure. Additionally, intrathecal administration delivers the vector directly to the cerebrospinal fluid, which facilitates widespread biodistribution and transduction within the CNS, while limiting systemic circulation. This reduces peripheral tissue exposure that may help lower the risk of off-target effects, including immune responses and systemic toxicities thereby potentially contributing to a more favorable safety profile. From the outset, our clinical development strategy has been deeply data-driven, with a focus on defining the most objective, clinically meaningful way to assess TASIA-102 across a broad patient population. Our robust analysis of the Rett syndrome natural history dataset demonstrated that after the age of six years, the likelihood of achieving defined developmental milestones across the core functional domains of Rett Syndrome is approximately 0%. This established the developmental plateau population. These important findings underpin our FDA-aligned pivotal trial design and allow us to objectively measure the functional aspects of TASHA-102 on essential activities of daily living. As I mentioned, we are pleased to have commenced site activation for our Reveal Pivotal Trial, which will assess the percentage of patients in the developmental plateau population who gain or regain one or more development milestones as part of the primary endpoint, with each patient serving as their own control. Based on the Part A data from our Reveal 1-2 trials, it's encouraging that all 10 patients treated with TASHA 102 gained or regained one or more developmental milestones, corresponding to a 100% response rate for the pivotal trial primary endpoint based on the May 25th data cutoff. With safety at the forefront, we are pleased to share the low and high dose of TASHA-102 continue to be generally well tolerated with no treatment related serious adverse events or dose limiting toxicities in the 12 patients treated as of August 2025 data cutoff. Lastly, We recently completed a public follow-on offering that resulted in total gross proceeds of $230 million, including full exercise of the underwriter's option to purchase additional shares, extending our cash runway into 2028. With our balance sheet strengthened, our pivotal trial underway, and a defined path to registration, we believe we are well-positioned to advance TASHA 102 to benefit patients living with this devastating disease. Our Revealed Clinical Development Program was designed to support the future approval of TASHA-102 for the treatment of females aged two years and older with Rett syndrome. Recall, Part A was our dose escalation phase, where we treated 12 patients aged six to 21 years, and our two Phase I-II Revealed trials with one of the two dose levels. The totality of the Part A data helped inform our discussions with the FDA and Health Canada on the optimal trial design for Part B, the pivotal phase of our trials. Our revealed pivotal Part B trial will evaluate developmental milestone gain and regain in the developmental plateau population. In parallel, we previously announced we aligned with the FDA on an extrapolation approach in a separate safety focus study evaluating Tayshia-102 in the pre-developmental plateau population of females aged two to less than six years. Given the high incidence of spontaneous milestone gains in this population, safety will be the primary focus and efficacy will be extrapolated from the developmental plateau population. Importantly, we believe this two-study approach allows us to generate safety and efficacy data across the broad Rett syndrome population while mitigating disease heterogeneity risk. Leveraging a pivotal trial design focused on targeted enrollment of patients within the developmental plateau population provides high statistical confidence given the approximately 0% likelihood of spontaneous milestone achievement in this population. From a CMC perspective, the Pivotal Tayshia 102 product has been released and cleared for use in our Revealed Pivotal trial. As previously disclosed, the FDA approved the use of the Pivotal lot, which is manufactured from the planned commercial manufacturing process, and agreed that it was comparable with the clinical material used in Part A. This achievement supports product consistency and quality, which are essential pillars of safety. Furthermore, this streamlines our path to initiating the pivotal trial and underscores our CMC readiness to support a future BLA submission. Our revealed pivotal trial for TASHA-102 will reflect a single-arm, open-label pivotal trial design with each patient serving as their own control. The high dose of TASHA-102 of 1e to the 15 total vector genomes will be evaluated, and we will enroll 15 females between the ages of 6 and less than 22 years in the developmental plateau population. As mentioned, the primary endpoint will assess the percentage of patients who gain or regain one or more developmental milestones from the list of 28 milestones across the core functional domains of communication, fine motor, and gross motor. Importantly, this responder definition was supported by the FDA and Health Canada as part of our recent feedback. With this established, we continue to believe Part A of our REVEAL trial supports the pivotal trial as well-powered to establish efficacy. We plan to conduct a six-month interim analysis in addition to a 12-month primary analysis, which could potentially expedite BLA submission by two to three quarters. Key secondary endpoints include the average number of total developmental milestones gained or regained per patient following TASHA 102, as well as clinician-assessed outcomes, including the RMBA and the CGII. These secondary endpoints are designed to capture the broad therapeutic outcomes across the domains of communication, fine motor, gross motor, and autonomic function that are central to the burden of disease. We are focused on site activation, which we anticipate will enable us to begin patient enrollment in the fourth quarter of this year. Importantly, our pivotal trial primary endpoint is an objective, clinically meaningful, and individualized assessment of function in the developmental plateau population. It was supported by caregiver research and natural history and has been aligned on with the FDA. As such, we believe achievement of this endpoint has the potential to redefine expectations and expand the possibilities of gene therapy for patients with Rett syndrome. With the pivotal trial now underway, it is important to understand the data-driven approach we took to defining this novel regulatory pathway, which was informed by the natural history and our revealed Part A clinical data. I will now turn the call over to Sukhu to discuss this. Sukhu?