Taysha Gene Therapies, Inc.

Good afternoon and welcome to the Taser Gene Therapy's third quarter 2023 earnings call. At this time all participants are in 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 and then zero on your telephone keypad. Please note that this call is being recorded. I'd now like to turn the call over to Haley Collins, the Director, Head of Corporate Communications and Investor Relations. Thank you, and you may proceed, Haley.

Thank you. Good afternoon, and welcome to Taysha's third quarter 2023 Financial Results and Corporate Update conference call. Earlier today, Taysha issued a press release announcing financial results for the third quarter 2023. 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 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 Tayshia-102 including the reproducibility and durability of any favorable results initially seen in our first and second patients dosed in the reveal trial, and including our preclinical product candidates to positively impact quality of life and also the course of disease in the patients we seek to treat in our research, development, and regulatory plans for our product candidates. These statements may include the expected timing and results of clinical trials for our product candidates and other clinical and regulatory plans. and the market opportunity for those 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. 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 that we have filed with the Securities and Exchange Commission, including our annual report on Form 10-K for the year ended December 31st, 2022, and our quarterly report on Form 10-Q for the quarter ended September 30th, 2023 that we filed today. The conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, November 14th, 2023. HACIA 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 2023 Third Quarter Financial Results and Corporate Update Conference Call. Today, I will begin with a brief update on our corporate and clinical activities. Then Dr. Sukhu Nagandran, president and head of R&D of Tayshia, will provide an update on the clinical development of our Tayshia 102 program. 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. This quarter, we continue to advance the clinical development of our lead gene therapy program in Rett Syndrome. including generating new clinical data in our adult trial in Canada and further engaging in regulatory discussions on our planned pediatric trials in the United States and United Kingdom. As a reminder, the REVEAL Phase 1-2 adult trial is a first in human study that was designed primarily to evaluate safety. Recall when we initiated the REVEAL trial in Canada, there was low expectation of efficacy for the stage four adult population among the KOLs in the Rett syndrome community due to the advanced and relentless progression of the disease. The focus was placed primarily on safety. Therefore, it was very exciting when we announced the encouraging initial impact that Tayshia-102 appeared to have across multiple clinical domains in the first adult patient treated. Today, we are pleased to share that as of the week 12 assessment, Patient 1 has demonstrated a sustained response in key efficacy measures and new improvements in several areas, including hand function, which is a hallmark manifestation of Rett syndrome. Additionally, the second adult patient treated also demonstrated a consistent early response across multiple clinical domains four weeks following treatment. The two patients have quite different genetic mutations. with the first patient's ME-CP2 mutation manifesting in a more severe disease phenotype than the second patient's mutation. Interestingly, while baseline characteristics and related assessments are very different between the two patients, for example, patient one was completely non-ambulatory, and patient two could walk with prompting. Both patients demonstrated an improvement across key clinical domains and presented similarly in a number of efficacy measures as early as week four following treatment. The principal investigator observed that both patients demonstrated improvements across clinical domains, including autonomic function, socialization, and gross and fine motor skills, with sustained and new improvements in the first patient at 12 weeks and initial improvements in the second patient four weeks following treatment. We believe these early improvements in both patients, coupled with the sustained response through week 12 in the first patient, support the transformational potential of TASHA-102 across multiple genotypes of Rett syndrome and further validate our construct. Sukhu will discuss the clinical observations and data in more detail. In addition to the positive clinical outcomes data, we are encouraged by the initial safety profile of TASHA-102. The data from the first adult patient showed TASHA-102 was well tolerated with no treatment emergent serious adverse events as of the 20-week assessment. And initial data from the second patient showed that TASHA-102 was well tolerated with no treatment emergent serious adverse events as of a six-week assessment. The Independent Data Monitoring Committee, or IDMC, recently convened to review the initial clinical data from the second patient dose with TASHA-102 following the patient's required 42-day evaluation period, as well as the 20-week clinical data from the first patient. Based on the encouraging clinical data, the IDMC recommended the continuation of the Reveal Phase 1-2 Adult Trial and provided clearance to dose the third patient in the first cohort, evaluating the low dose of TASHA-102. Looking ahead, we remain focused on further exploring the initial therapeutic potential of TASHA-102 across different ages and geographies. We expect to dose the third adult patient and complete dosing in the low dose cohort in either the fourth quarter of 2023 or the first quarter of 2024. Expansion of the TASHA-102 into earlier stages of the disease remains on track, with dosing of the first pediatric patient in our planned U.S. trial anticipated in the first quarter of 2024. Additionally, we expect to receive a response from the UK MHRA on our clinical trial application submission for TASHA-102 in pediatric patients with Rett syndrome by the end of this year. We recently entered into a loan and security agreement with Trinity Capital that includes no financial covenants or warrants and terminated our existing loan and security agreement with Silicon Valley Bank. This has extended our cash runway by one quarter into 2026, which will further support the clinical development of TASHA 102. Cameron will provide more details on the agreement. With the extension of our runway and encouraging clinical data in TASHA 102, we believe we are well-positioned to execute across our key value-creating milestones. Moving forward, we plan to continue to advance TASHA 102 program in an effort to bring a potentially transformational treatment to patients living with this devastating disease. I will now turn the call over to Sukhu to provide a more in-depth discussion on our clinical program in Rett syndrome.