Release Date: August 12, 2024
For the complete transcript of the earnings call, please refer to the full earnings call transcript.
Positive Points
- Encouraging safety and efficacy data from the low-dose cohort in both REVEAL Phase 1/2 trials.
- Initiation of the high-dose cohort and expansion of the pediatric trial into Canada.
- Strengthened balance sheet with $76.8 million in net proceeds from a public follow-on offering.
- TSHA-102 demonstrated a well-tolerated safety profile with no serious adverse events or dose-limiting toxicities.
- Potential transformative therapeutic option for Rett syndrome, addressing a significant unmet medical need.
Negative Points
- Dependence on strategic alliances and third-party relationships for development.
- Uncertainties related to the timing and results of clinical trials and regulatory interactions.
- High costs associated with research and development activities.
- Complexity in treating Rett syndrome due to the heterogeneous nature of the disease.
- Potential challenges in demonstrating a clear dose-response relationship in clinical trials.
Q & A Highlights
Q: When you report the high-dose data next year, what in your opinion is going to be the best way to determine if there is a dose response?
A: Sean Nolan, CEO: We expect to see consistent effects across all clinical domains. The low dose has set a high bar, and we anticipate the high dose will build on that. The preclinical data showed increased survival and improved gait abnormalities at the high dose. We will use the same endpoints and observation mechanisms to capture the data consistently. Suku Nagendran, President and Head of R&D, added that the data will ultimately drive the determination of the ideal dose.
Q: Can you comment on how the dialogue is going with the regulatory authorities?
A: Sean Nolan, CEO: We have an upcoming Type B meeting due to the RMAT designation. Our goal is to align on the cadence of interfacing with the agency and focus on priorities. We aim to share data in real-time and discuss trial design and endpoints for Part B.
Q: What is the time frame for the data you plan to present in the first half of next year?
A: Sean Nolan, CEO: We plan to have a minimum of six months of data for the majority of patients in each cohort. This will provide a more consistent and fulsome update.
Q: How will you handle the variability in patient responses given the heterogeneity of Rett syndrome?
A: Sean Nolan, CEO: We are considering standardized primary or co-primary endpoints while also capturing data on the restoration of function. Suku Nagendran, President and Head of R&D, added that consistent positive clinical impacts have been observed, and natural history data will further support the trial design.
Q: Can you explain the change in your data disclosure strategy?
A: Sean Nolan, CEO: Initially, we reported early data due to the company's financial situation. Now, with a stronger balance sheet, we aim to present data on a cohort-by-cohort basis. We believe this approach provides a more robust and comprehensive view of the data.
Q: Does the timeline change for data impact your timeline for an end of Phase 1 meeting with the FDA?
A: Sean Nolan, CEO: We aim to complete cohort 2 dosing and natural history analysis before the end of Phase 1 meeting. The goal is to have a detailed discussion with the FDA in the first half of 2025, but the exact amount of data needed is still being determined.
Q: Are there any more details on the SAE observed in the pediatric patient related to the immunosuppressive regimen?
A: Sean Nolan, CEO: The SAE was not related to our product and has resolved. The IDMC has allowed us to proceed with dosing.
Q: What are the baseline characteristics of the high-dose patients enrolled in the study?
A: Sukumar Nagendran, President and Head of R&D: The patients fall into a CGI-S range of 4 to 6. Common clinical features include autonomic dysfunction, respiratory abnormalities, seizures, and loss of hand function. The natural history data will further support our understanding.
Q: How do you expect the low-dose data to evolve over time?
A: Sean Nolan, CEO: We hope to see continued improvements in gross motor skills, hand function, and communication over time, especially in younger patients. The data will be reported in the first half of next year.
Q: Could the safety committee accelerate or remove the staggered dosing period?
A: Sean Nolan, CEO: The staggered dosing period is currently 42 days. We are discussing with the IDMC the possibility of changing this based on continued good safety results.
For the complete transcript of the earnings call, please refer to the full earnings call transcript.
