Taysha Gene Therapies, Inc.

Greetings and welcome to the Tayshia Gene Therapy's second quarter 2024 earnings call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star 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 and Head of Corporate Communications and Investor Relations. Thank you. You may begin.

Thank you. Good morning and welcome to Tayshia's second quarter 2024 financial results and corporate update conference call. Earlier today, Tayshia issued a press release announcing financial results for the second quarter ended June 30th, 2024. 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, Tayshia's CEO, 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 relating to the therapeutic and commercial potential of TASHA-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 the 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 timelines for our clinical trials and reporting results therefrom, and our current cash resources supporting our planned operating expenses and capital requirements into the fourth quarter of 2026. These statements may include, but are not limited to, the expected timing and results of clinical trials for our product candidates and other clinical and regulatory plans, and the market opportunities for those programs. This call may also contain forward-looking statements relating to Tayshia'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 Tayshia's actual results to differ materially from those stated or implied in such forward-looking statements. These risks include uncertainties related to the timing, and results of clinical trials of and regulatory interactions for our product candidates, our dependence upon strategic alliances and other third-party relationships, our ability to obtain patent protection for our discoveries, limitations imposed by patents owned or controlled by third parties, and the requirements of substantial funding to conduct our research and development activities. 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 the Form 10Q, the full year ended December 31st, 2023, in our quarterly report on Form 10Q for the quarter ended June 30th, 2024 that we filed today. This conference call contains time sensitive information that is accurate only as of the date of this live broadcast, August 12th, 2024. TASHA 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 second quarter 2024 Financial Results and Corporate Update conference call. Today, I will begin with a brief update on our recent activities and then, Sukku, Our president and head of R&D will provide an update on our lead TASHA 102 program in 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. In the second quarter of 2024, we made strong progress across the TASHA 102 program in clinical evaluation for pediatric, adolescent, and adult patients with Rett syndrome. This included reporting encouraging safety and efficacy data from the low-dose cohort in both our Reveal Phase 1-2 trials, initiating the high-dose cohort, expanding our pediatric trial into Canada, and strengthening our balance sheet. With this progress, we believe we are well-positioned to execute across key value-creating milestones in our CASIA 102 program. Our goal is to develop potentially transformative therapy options for all patients suffering from Rett syndrome. We remain steadfast and focused on clinical trial execution and data collection across a broad range of ages and stages of patients with Rett syndrome, which will further inform our discussions with regulatory authorities on the development plan for the next phase of our studies. As a reminder, Rett syndrome is a rare neurodevelopmental disorder that afflicts an estimated 15 to 20,000 patients in the United States, European Union, and United Kingdom. Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease, and there is significant unmet need. Rett syndrome is caused by mutations in the X-linked ME-CP2 gene, which results in the neural network dysfunction and leads to multi-system complications. It's characterized by loss of communication and hand function, slowing and or regression of development, motor and respiratory impairment, seizures, intellectual disabilities, and shortened life expectancy. Individuals with Rett syndrome typically require 24-7 care and lifelong assistance with daily activities, resulting in high caregiver burden, and significant impact on quality of life. Artesia 102 gene therapy candidate is a one-time intrathecally delivered treatment designed to address the underlying cause of the disease. Rett syndrome is challenging to treat with traditional small molecule and gene therapy approaches due to the random X inactivation and subsequent mosaic expression pattern of MECP2 that results in a mixture of cells that are either deficient in MECP2 or express MECP2 normally. We believe TASHA-102, equipped with the novel MI Rare technology, has the potential to appropriately address this challenge by mediating MECP2 expression in the central nervous system on a cell-by-cell basis to overcome the risks associated with both under- and overexpression of MECP2. Recall, we have two ongoing Phase 1-2 reveal trials evaluating TASHA-102, an adolescent and adult trial taking place in Canada and the U.S. for patients 12 and older with stage 4 RUT syndrome, which is the most advanced stage of the disease, and a pediatric trial taking place in the U.S. and U.K. with recent clearance in Canada for patients 5 to 8 years of age with stage 3 Rett syndrome. We are currently enrolling patients in Part A, the dose escalation portion of both trials, which is evaluating two dose levels of TASHA-102. Part B of the pediatric trial, the dose expansion portion, will evaluate TASHA-102 in two age cohorts, an expanded five to eight years of age cohort and a three to five years of age cohort. Two patients have been dosed in cohort one, which is evaluating the low dose of TASIA-102, 5.7 e to the 14 total vector genomes in each trial. At the 2024 Rett Syndrome Foundation Rett Syndrome Scientific Meeting in June, we reported encouraging preliminary data from cohort one in our pediatric trial and longer-term data from cohort one in our adolescent and adult trials. which demonstrated a well-tolerated safety profile and improvements across consistent clinical domains impacting daily activities in the adult and the pediatric patients treated with the low dose of TASHA-102. We are pleased by the consistent clinical response demonstrated across multiple areas of disease, including autonomic function, seizures, gross motor skills, fine motor skills and hand function, and communication and socialization in both adult and pediatric patients with different genetic mutation severity. We look forward to continuing to evaluate the clinical impact of the low dose of TASHA-102 over time. Following review of these data, the Independent Data Monitoring Committee, or IDMC, approved our request to dose escalate early in both reveal trials. Therefore, dosing in cohort one of both trials is complete. Expediting dose escalation is an important step in our development plan as advancing earlier to the high dose accelerates our ability to further inform our clinical development and regulatory strategy for the next phase of our studies. With cohort one complete, we've turned our focus to dosing patients in the high dose cohort across both are reveal trials, and building on our promising preliminary low-dose data set from both adult and pediatric populations. We dose the first patient in cohort two of our adolescent and adult trial, which is evaluating the high dose of TASHA-102, which is 1E to 15 total vector genomes. We are pleased to share that the high dose of TASHA-102 was generally well-tolerated with no serious adverse events for dose-limiting toxicities as of the patient's initial six weeks assessment. Following review of these data, the IDMC provided clearance to proceed with the dosing the second patient in cohort two of the adolescent and adult trial and the first patient in cohort two of the pediatric trial earlier than planned. Subsequently, we enrolled the second adolescent adult patient and the first pediatric patient in cohort two across both trials. Dosing of both patients is scheduled to occur in the third quarter of 2024. Lastly, we strengthened our balance sheet with the recent completion of a public follow-on offering that resulted in total net proceeds of $76.8 million. We expect the net proceeds to extend our anticipated cash runway into the fourth quarter of 2026 to support the continued development of our TASHA 102 program. Importantly, this capital infusion allows us to build on our preliminary TASHA 102 clinical data set in the adult and pediatric patients and enables us to focus on execution as we endeavor to deliver on key value-creating milestones. We are moving forward reporting cohort-based updates with more mature data sets in order to provide more fulsome updates on our clinical data. In line with this decision, we plan to report safety and efficacy data from the high-dose cohorts and an update on the safety and efficacy from the low-dose cohorts in both our adolescent and adult trial and our pediatric trial in the first half of 2025. With our balance sheet strengthened and cash runway extended, we believe we are in excellent position to execute on our key upcoming milestones. I will now turn the call over to Sukhu to provide a more in-depth discussion of our TASHA-102 program.