Taysha Gene Therapies, Inc.

Ladies and gentlemen, good morning and welcome to the Tayshia Gene Therapy's full year 2024 conference call. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require 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 and Investor Relations. Please go ahead.

Thank you. Good morning and welcome to Tayshia's full year 2024 financial results and corporate update conference call. Earlier today, Tayshia issued a press release announcing financial results for the full year ended December 31st, 2024. 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. Please note that 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 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 initiating additional trials and reporting data from our clinical trials, the potential for the product candidate to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, the clinical potential of intrathecal administration, the market opportunity for our programs, and the 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 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 TACIA'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 Securities and Exchange Commission, including in our annual report on Form 10-K for the full year ended December 31, 2024, that we filed today. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast. February 26, 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 full-year 2024 financial results and corporate update conference call. I will begin with a brief update on our recent activities. Then Dr. Sukhu Nagendran, president and head of R&D of Tayshia, will provide an update on our lead Tayshia 102 gene therapy program and clinical evaluation for Rett syndrome. Cameron Alam, our chief financial officer, will follow up with a financial update. And I will provide closing remarks and open the call up for questions. The past year, has been marked by exceptional execution as we have focused on generating critical, longer-term clinical data across our two Reveal Phase 1-2 trials to further elucidate the therapeutic potential of TASHA-102 and inform the development plan for the next phase of the trials. We are pleased with the pace at which our TASHA-102 program is advancing across a broad range of ages and stages of patients with Rett syndrome. Importantly, We believe the progress we have made has set the stage for a highly impactful 2025 as we focus on advancing TASHA-102 toward the pivotal phase of the reveal trials. I am pleased to share that both the high and low dose of TASHA-102 continue to demonstrate an encouraging safety profile. TASHA-102 was generally well tolerated with no treatment related serious adverse events or dose limiting toxicities in the 10 pediatric, adolescent, and adult patients dosed across our two Reveal trials as of the February 2025 data cutoff. Importantly, we have completed dosing of the 10 patients in Part A, the dose escalation portion of the Reveal Phase 1-2 adolescent, adult, and the Reveal Phase 1-2 pediatric trial. This includes six patients in Cohort 2 evaluating the high dose of TASHA-102 at 1e to the 15 total vector genomes, and four patients in cohort one evaluating the low dose of TASHA-102 of 5.7e to the 14 total vector genomes. This maturing dataset continues to support our advancement toward the pivotal Part B trial as part of our ongoing discussions with the FDA. From the outset, our strategy has been to utilize Part A of our trials to generate a dataset that informs our development plan for Part B, which is the pivotal phase of the trials. With dosing of the 10 patients in Part A complete, we believe we have a strong, maturing data set in hand that enables us to further solidify the regulatory pathway for TASHA 102 with the FDA. Previously, we announced that following regulatory meetings with the FDA regarding our ongoing TASHA 102 development plan, We intend to focus on objective measures that clinically capture improvements in the core features of Rett syndrome in Part B of our revealed trials. Recall, the clinical data presented from the adult and pediatric patients with varying genotypes and disease severity, including those with the most advanced stage of Rett syndrome treated with the low dose of TASHA-102, consistently showed clinical improvements and functional gains across multiple domains, as early as four weeks post-treatment that persisted and strengthened over time. This included improvements in functional gains across the domains of fine and gross motor function, socialization and communication, autonomic function, and seizure events. Importantly, The functional gains consistently seen in the treated patients that we've reported to date directly represent improvements in activities of daily living that are meaningful to caregivers. Since then, to further assess the therapeutic potential of TASHA-102, we have continued to evaluate the four patients in the low-dose cohort and have expanded our data set by completing dosing of the six pediatric, adolescent, and adult patients in the high-dose cohort. We continue to believe that functional outcome are the most relevant, objective, and clinically meaningful assessments of the treatment effect of TASHA-102 in patients with Rett syndrome, where functional gains or restoration of loss in function are not expected to occur in the untreated population. As such, based on our ongoing discussions with the FDA and the totality of the clinical data we have collected, Our goal is to advance TASHA 102 toward a pivotal trial design that objectively assesses functional gains across key clinical domains impacted in Rett syndrome to bring TASHA 102 to patients as expeditiously and as safely as possible. We remain encouraged by our productive, ongoing discussions with the FDA through the Regenerative Medicines Advanced Therapy, or RMAT, mechanism and the strong maturing data set we have in hand that provides us the further ability to solidify the regulatory pathway for TASHA 102. We look forward to providing an update on the pivotal Part P trial design in the first half of 2025. We also expect to provide an update on the clinical data from the low and high dose cohorts across our adolescent adult trial as well as our pediatric trial in the first half of 2025. As we prepare for these critical milestones, we remain highly confident in our differentiated gene therapy candidate, which we believe has the potential to provide meaningful benefit to a broad population of patients with Rett syndrome using a minimally invasive delivery approach. I will now turn the call over to Sukhu to provide more context on these advancements that further support our development approach for TASHA-102. Sukhu?