Taysha Gene Therapies, Inc. (TSHA)·Q4 2024 Earnings Summary

Executive Summary

• Completed dosing of all 10 Part A patients (high dose n=6; low dose n=4) across both REVEAL Phase 1/2 trials; TSHA-102 remained generally well tolerated with no treatment‑related SAEs or DLTs as of the February 2025 cutoff .
• Regulatory path continued to progress: ongoing RMAT-enabled FDA dialogue with an update on pivotal Part B design and primary endpoint planned for 1H 2025; management emphasized objective functional gains as the core of the pivotal strategy .
• Financially, FY 2024 revenue was $8.33M vs. $15.45M in FY 2023, net loss improved to $89.30M vs. $111.57M in 2023, and year-end cash was $139.04M with runway into 4Q26 (maintained) .
• Near-term stock catalysts: (1) pivotal Part B design/endpoints alignment with FDA, (2) Part A high- and low-dose clinical data updates (adolescent/adult and pediatric) in 1H 2025, (3) clarity on immunosuppression for Part B (potential to simplify to short-course steroids) .

What Went Well and What Went Wrong

What Went Well

• Clean safety/tolerability across both dose levels: “no treatment‑related serious adverse events (SAEs) or dose‑limiting toxicities (DLTs)” (n=10) and recent IDMC review supportive; management reiterated typical IT gene therapy LFT elevations are mild and controlled with steroids .
• Regulatory engagement constructive and consistent; FDA has encouraged continued dataset maturation and use of natural history to contextualize functional gains; pivotal design update targeted for 1H 2025 .
• CMC readiness remains a relative strength (from prior quarter): FDA previously endorsed commercially intended process; pivotal product released for use in trials based on analytical comparability, supporting readiness for Part B .

Quotes

• “TSHA-102 continues to be well tolerated… With dosing of the 10 patients in Part A… we have a strong, maturing dataset in hand to further solidify the regulatory pathway…” — Sean P. Nolan, CEO .
• “We intend to focus on objective measures that clinically capture improvements in the core features of Rett Syndrome in Part B…” — Management on pivotal approach .

What Went Wrong

• Topline still largely non-commercial: FY revenue declined to $8.33M from $15.45M in FY 2023, reflecting dependency on collaboration/deferral mechanics; quarterly revenue lens shows modest variability (see Financial Results) .
• Operating spend increased y/y on R&D (GMP/commercial process and clinical activities), with an impairment charge; although net loss improved y/y, burn remains meaningful pre-pivotal .
• Regulatory endpoint specifics not yet finalized; while FDA dialogue is positive, investors remain focused on endpoint choice/thresholds and competitor read‑throughs; company will disclose once alignment is achieved .

Financial Results

Quarterly performance (selected P&L items)

Note: TSHA reports full-year results for Q4; Q4 2024 revenue and net loss are derived from FY and 9M data (see citations).

• Q4 2024 vs. Q3 2024: Revenue +13.1% q/q; Net loss improved q/q (smaller loss) on a derived basis .
• Q4 2024 vs. Q4 2023: Company did not provide Q4 2023 standalone; FY comps below provide context .

Full-year comparison

KPIs and clinical execution indicators

Guidance Changes

Note: No quantitative revenue, margin, tax rate, or OpEx guidance was provided; cadence relates to clinical/regulatory milestones and liquidity runway .

Earnings Call Themes & Trends

Management Commentary

• “Our goal is to advance TSHA‑102 toward a pivotal trial design that objectively assesses functional gains across key clinical domains impacted in Rett syndrome…” — CEO .
• “TSHA‑102 was generally well tolerated with no treatment related serious adverse events or dose limiting toxicities in the 10… patients dosed across our two REVEAL trials…” — CEO .
• “The FDA has been very… open‑minded to the data… [CGI/CGI‑S] can be informative, but… are also very subjective… you wouldn’t set up a single arm trial… to use those as a primary endpoint.” — CEO .
• “We recently shared our natural history data assessments with the FDA and that is part of the ongoing discussion.” — CEO .
• “From a CMC perspective, we’re very comfortable… the FDA has effectively endorsed our commercially intended process. We’ve got product in the freezer that we can utilize.” — CEO .

Q&A Highlights

• FDA alignment and endpoint choice: Management aims to couple pivotal design disclosure with data in 1H25; FDA consistent and constructive, favoring objective, clinically meaningful functional gains; no hierarchy among domains (communication/socialization, fine/gross motor, seizures) .
• Safety window/context: Most gene therapy acute AEs occur in first 2–6 weeks; recent IDMC review across 10 patients; IT approach generally mild LFT elevations controlled with steroids .
• Competitive differentiation: Self‑complementary construct expected to drive faster protein expression and earlier functional gains; minimally invasive IT administration highlighted .
• Disclosure cadence: Expect longer‑term low‑dose data (≥1 year on therapy) and majority of high‑dose patients with ≥6 months follow‑up in 1H25; natural history contextualization to be included .
• Immunosuppression: Currently steroids + sirolimus (~6‑month taper); Part B may drop sirolimus and use short‑course steroids only, pending internal assessment .

Estimates Context

• Wall Street consensus (S&P Global) for Q4 2024 EPS and revenue was unavailable at time of analysis due to access limits. We attempted to retrieve via S&P Global GetEstimates but hit a daily request limit. If needed, we can refresh and add an estimates vs. actuals comparison upon availability [GetEstimates error: Daily Request Limit Exceeded].

Key Takeaways for Investors

• Safety/tolerability profile through Part A (n=10) is a core de‑risking event ahead of pivotal; no treatment‑related SAEs/DLTs supports dose selection and Part B readiness .
• Regulatory path hinges on objective functional gains with natural history corroboration; clarity on primary endpoint and design in 1H25 is the key near‑term catalyst .
• CMC validation and pivotal product availability mitigate a frequent gene therapy bottleneck; supports smoother transition into pivotal execution .
• Potential simplification of immunosuppression in Part B (steroid‑only) could improve risk/benefit and operational ease if adopted .
• Financial runway into 4Q26 provides time to execute pivotal transition, but operating intensity will remain elevated; no commercial revenue yet, with FY revenue down y/y and ongoing losses typical of clinical stage .
• Competitive dynamics remain in focus; management positions TSHA‑102 as potentially faster‑onset and broadly active across severities with minimally invasive delivery—pivotal endpoint selection will be central to differentiation .
• Trading setup: Expect event‑driven volatility around the 1H25 pivotal design and data updates; confirmation of endpoints and magnitude of functional gains will likely drive estimate revisions and rerating.

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Appendix: Additional Context and Cross-Checks

• Full‑year 2024 results communicated via press release (Ex. 99.1) furnished under Item 2.02 of the 8‑K; CFO remarks on the call matched the reported figures (R&D $66.0M; G&A $29.0M; net loss $89.3M; cash $139.0M; runway into 4Q26) .
• Quarterly derivations: Q4 2024 revenue ($2.022M) = FY revenue ($8.333M) − 9M revenue ($6.311M); Q4 2024 net loss ($18.785M) = FY net loss ($89.298M) − 9M net loss ($70.513M) .