Taysha Gene Therapies, Inc. Q3 FY2024 earnings call

• Continued progress in the TSHA-102 program for Rett Syndrome, including achieving clinical and CMC regulatory milestones, collecting clinical data supporting the safety profile of TSHA-102 across different ages and disease stages, and enrolling additional patients in the high-dose cohort of REVEAL Phase 1/2 trials. - Completed a Type B multidisciplinary meeting with the FDA regarding the RMAT designation for TSHA-102, advancing discussions on trial design, endpoints, and the use of a natural history dataset. - Finished a Type D CMC meeting, obtained FDA approval to use the pivotal TSHA-102 product in REVEAL trials, and received approval from the IDMC to continue enrolling in the high-dose cohort. - Aligned on a meeting cadence with the FDA to expedite TSHA-102 development and determined that RSVQ will not be a primary or secondary endpoint in Part B of the REVEAL trials as per FDA feedback.

Research and development expenses for the three months ended September 30, 2024, were $14.9 million, compared to $11.8 million in the same period of 2023. The increase was driven by a $0.8 million rise in GMP batch activity related to the commercial manufacturing process for TSHA-102 and higher compensation for R&D employees, partially offset by lower consultant and contractor expenses. General and administrative expenses were $7.9 million for the three months ended September 30, 2024, down from $8.6 million in 2023, primarily due to reduced issuance costs from liability-classified 2023 pre-funded warrants. Net loss for the quarter was $25.5 million or $0.10 per share, versus a net loss of $117.1 million or $0.93 per share in the third quarter of 2023. The reduction in net loss in 2024 was mainly because of a non-cash loss of $100.5 million in 2023 from a change in fair value of warrant liability. As of September 30, 2024, Taysha had $157.7 million in cash and cash equivalents, and the company expects its current cash resources to support planned operating expenses and capital requirements into the fourth quarter of 2026.

• Anticipate reporting longer-term data from the low-dose and high-dose cohorts in both REVEAL trials in the first half of 2025. - Plan to continue working closely with the FDA through the RMAT mechanism to solidify the regulatory pathway for TSHA-102. - Current cash resources are expected to support operating expenses and capital requirements into the fourth quarter of 2026.

• Uncertainties related to the timing and results of clinical trials and regulatory interactions for product candidates. - Dependence on strategic alliances and other third-party relationships. - Limitations in obtaining patent protection for discoveries and the need for substantial funding to conduct research and development activities.

Q: Kristen Kluska from Cantor Fitzgerald inquired about regulatory endpoints considering the heterogeneous nature of the disease.

A: Sean Nolan responded that heterogeneity is taken into account, with considerations such as looking at the patient as their own control, analyzing natural history, and focusing on milestones, functional gains, hand function, and gross motor function as objective measures.

Q: Chris Raymond from Piper Sandler asked about natural history analysis and the use of RSVQ.

A: Sean Nolan and Sukumar Nagendran discussed natural history analysis and the high variability of RSVQ, stating it is not a viable endpoint.

Q: Whitney Ijem from Canaccord Genuity asked about the demand for high-dose enrollment and treatment logistics.

A: Sean Nolan and Sukumar Nagendran talked about significant demand for high-dose enrollment and the treatment day logistics, including the immunomodulatory regimen and the timeline of the procedure.

Q: Salveen Richter from Goldman Sachs asked about the specific objective measures in Part B of the REVEAL study.

A: Sean Nolan stated that they are working towards final alignment with the FDA and will provide updates later when fully aligned.

Q: Gil Blum from Needham & Co. asked about synergies from Zolgensma experience in the Type D meeting and pivotal study design.

A: Sean Nolan discussed the comparability between the clinical and commercial processes and the consideration of multiple trial designs.

Q: Maury Raycroft from Jefferies asked about Part A data updates and including younger patients in Part B.

A: Sean Nolan mentioned ongoing alignment with the FDA and the intent to include younger patients in Part B.

Q: Unidentified Analyst from Wolf Fargo asked about Neurogene data and dosing above the high-dose.

A: Sean Nolan and Sukumar Nagendran discussed the comparability of Neurogene data and the potential for higher dosing.

Q: Jack Allen from Baird asked about high-dose patients and the sites where they were dosed.

A: Sean Nolan and Sukumar Nagendran discussed the number of sites and patient dosing in the high-dose cohort.

Q: Joon Lee from Truist Securities asked about RSVQ updates and endpoints in Part A.

A: Sean Nolan stated that RSVQ updates are no longer provided and the focus is on functional gains.

Q: Silvan Tuerkcan from Citizens JMP asked about Neurogene data and biodistribution.

A: Sean Nolan and Sukumar Nagendran discussed the equivalence of biodistribution and alignment of clinical data.

Q: Keith Tapper from BMO Capital Markets asked about the motivation for the high-dose cohort and translatability between pediatric and adult patients.

A: Sean Nolan discussed the benefits of the high-dose, safety margin, and the expected translatability between pediatric and adult patients' responses to treatment