Taysha Gene Therapies, Inc. (TSHA) Earnings

Management highlights

- Clinical Development Milestones * Completed dosing in both the over-enrolled REVEAL Pivotal trial (17 total patients dosed) and the ASPIRE safety trial, with a balanced age distribution across pediatric, adolescent, and adult patients matching the broader Rett Syndrome population * Presented longer-term follow-up data from REVEAL Part A at the 2026 IRSF Rett Syndrome Scientific Meeting: all 12 treated patients had ≥12 months of follow-up, with a 100% response rate (meeting the FDA-aligned 33% threshold for the pivotal trial endpoint) at 12 months, and treatment effects continued to deepen with no plateau observed * Confirmed a favorable, consistent safety profile: across 33 total treated patients as of August 2026, no severe treatment-related serious adverse events (SAEs) or dose-limiting toxicities have been observed in over three years of clinical testing * Presented supporting data at IRSF confirming the REVEAL Pivotal trial design: natural history data shows developmental milestone gain probability drops to <6.7% for patients over 6 years of age, validating the trial's inclusion criteria and endpoint; the Developmental Milestone Assessment (DMA) primary endpoint was confirmed as psychometrically valid and FDA-aligned - Manufacturing and Commercial Readiness * Expanded the long-standing partnership with Catalent to make Catalent the primary commercial manufacturing partner for Tayshia-102, securing scalable long-term manufacturing capacity at Catalent's FDA-licensed Maryland gene therapy campus, with BLA-enabling PPQ activities currently underway * Completed payer market research that demonstrated strong payer support for Tayshia-102's value proposition, driven by its one-time, minimally invasive intrathecal outpatient administration, favorable safety profile, and potential for durable transformative disease modification; payers identified durable functional improvements as the top determinant of coverage and reimbursement * Strengthened leadership with the appointment of a new Chief Legal Officer with 30+ years of gene therapy industry experience, supporting the company's next phase of growth toward commercialization - Finances * Completed a successful follow-on financing in June 2026 that raised $230 million in gross proceeds, strengthening the company's balance sheet

Guidance

- Completion of the BLA-enabling PPQ manufacturing campaign remains on track for Q4 2026 - Top-line data from the REVEAL Pivotal six-month interim analysis, plus FDA feedback on the BLA submission pathway, is expected to be reported in the first half of 2027 - The interim analysis could support an earlier BLA submission, accelerating the timeline by at least two quarters compared to submission based on 12-month data - Current cash resources are expected to fund all planned operating activities and capital requirements into the second half of 2028, through potential BLA approval

Segment performance

Tayshia Gene Therapies is a clinical-stage biotech focused exclusively on the development of Tayshia-102 for Rett Syndrome, with no other commercial product segments. For Q2 2026, the company reported total research and development expenses of $38.6 million, an increase of $18.5 million from $20.1 million in Q2 2025, driven by BLA-enabling process performance qualification (PPQ) manufacturing activities and higher clinical trial costs for the REVEAL Pivotal and ASPIRE trials, plus increased compensation from expanded R&D headcount. General and administrative expenses were $12.1 million in Q2 2026, up $3.5 million from $8.6 million in Q2 2025, primarily due to higher compensation and commercial launch readiness costs. The company reported a net loss of $46.6 million (13 cents per share) in Q2 2026, compared to a net loss of $26.9 million (9 cents per share) in Q2 2025. As of June 30, 2026, Tayshia held $455.4 million in cash and cash equivalents.

Risks & headwinds

- Clinical development and regulatory risk: Final results from the REVEAL Pivotal interim analysis may not match the positive efficacy and safety signals seen in earlier Part A data, and the FDA may not agree to accept an accelerated submission based on the six-month interim data or approve Tayshia-102 based on the submitted data - Safety risk: AAV9-based gene therapies carry a known risk of peripheral sensory neuropathy, which occurred as a Grade 2 treatment-related SAE in one REVEAL Pivotal patient; while the patient recovered quickly, future cases could impact the benefit-risk profile and regulatory approval - Reimbursement risk: Despite positive early payer research, payers may ultimately reject coverage or set unfavorable reimbursement terms if they judge the demonstrated clinical benefit to be insufficient - Manufacturing risk: The company relies on a single third-party manufacturing partner for commercial supply, and unexpected manufacturing issues could delay launch or limit supply after approval

Analyst Q&A

• Q: What specific feedback did payers provide on Tayshia-102's intrathecal outpatient administration, beyond its general value proposition? /

  A: Payers specifically noted that intrathecal administration is far less invasive than alternative direct-to-CNS delivery methods for gene therapy. They also highlighted that outpatient administration supports attractive reimbursement margins for payers and enables broader scalable access to more patients, making the therapy economically attractive relative to other potential gene therapy products for Rett Syndrome. The top factors driving payer support remained durable clinical benefit, strong safety data, and transformative disease modification in a high unmet need population.

• Q: What is the context of the reported Grade 2 peripheral neuropathy SAE, how is it managed, and what mitigation steps are in place? /

  A: This is a known expected risk with AAV9-based gene therapies, and over 50% of Rett Syndrome patients already experience peripheral neuropathy as part of their disease course. The event was moderate Grade 2, the patient was treated with standard immunomodulatory agents, and recovered substantially within 24 hours of discharge. Prophylactic immunomodulatory treatment is already standard in the trial protocol, which reduces the incidence of such events. The event was reported to the FDA and the trial's IDMC, and neither raised concerns or requested protocol changes.

• Q: What is the status of seizure activity data collection, and can seizure benefit be included in the eventual Tayshia-102 label? /

  A: Preliminary Part A data shows an overall reduction in seizure frequency and severity, plus reduced anticonvulsant dosing, but this data is still being analyzed and will likely be presented at a major medical meeting in late 2026 or early 2027. In the REVEAL Pivotal trial, baseline and post-treatment EEG data and seizure history are collected as an exploratory endpoint, not a primary or secondary endpoint. This will generate a signal of potential benefit, but will not provide definitive data for a label claim at this stage. To date, no worsening of seizure activity has been observed.

• Q: What remaining CMC activities are on the critical path to BLA submission, and what does FDA-agreed comparability mean for the regulatory process? /

  A: The FDA has already confirmed that the commercial-scale manufacturing process produces product that is analytically comparable to the clinical material used in the REVEAL Part A trial, which allows the company to use existing Part A efficacy and safety data to support the BLA submission. All major CMC activities including assay validation are complete, with the only remaining critical path item being completion of the PPQ manufacturing runs, which are on track for Q4 2026. The company stated it is in a strong position on CMC with no outstanding major issues.