Executive Summary

Q1 2025 beat on both revenue and EPS vs S&P Global consensus: revenue $2.30M vs $1.35M consensus (+71%), EPS ($0.08) vs ($0.09) consensus; beats driven by collaboration/deferred revenue recognition with disciplined OpEx control. Bold beat on both lines [*S&P Global].
Regulatory inflection: Written FDA alignment on key elements of the pivotal Part B design for TSHA-102; FDA advised submitting the protocol/SAP as an IND amendment (no end-of-phase meeting), potentially accelerating initiation; submission expected in Q2 2025 .
Safety/tolerability remains favorable: Across 10 patients (high dose n=6; low dose n=4), no treatment-related SAEs or DLTs as of Apr 10, 2025; management reiterated confidence in high-dose profile and trajectory to pivotal .
Near-term catalysts: Part B protocol/SAP submission (Q2 2025), pivotal initiation activities (Q3 2025), and comprehensive program update (pivotal design, natural history analysis, and REVEAL cohorts) alongside the IRSF Scientific Meeting in Q2 2025 .

What Went Well and What Went Wrong

What Went Well
- FDA alignment: “We obtained written alignment from the FDA on key elements of our pivotal Part B trial design... FDA advised us to proceed directly to submitting our pivotal trial protocol and... SAP as an amendment to the IND... eliminating the need for a formal end-of-phase meeting.” — CEO Sean Nolan .
- Safety maintained at scale: No treatment-related SAEs/DLTs across 10 patients (high n=6; low n=4) in REVEAL; high/low dose generally well tolerated .
- Visibility into pivotal path: Management emphasized objective, non–effort-based primary endpoint with blinded, video-based assessments; single-arm framework with robust bias mitigation discussed on the call .
What Went Wrong
- Year-over-year revenue decline: Q1 revenue fell to $2.30M from $3.41M in Q1 2024 as collaboration/deferred revenue cadence moderated .
- Operating costs up sequentially: Total operating expenses rose to $23.72M from $21.95M in Q4 2024 as programs advanced toward pivotal, though down vs Q3 2024 which included an impairment .
- Continued net losses: Q1 net loss was ($21.53)M; though improved YoY, TSHA remains dependent on external capital over time despite runway into Q4 2026 .

Financial Results

P&L and Cash (oldest → newest)

Metric	Q3 2024	Q4 2024	Q1 2025
Revenue ($USD)	$1.79M	$2.02M	$2.30M
Net Loss ($USD)	($25.52)M	($18.79)M*	($21.53)M
Diluted EPS ($)	($0.10)	($0.07)*	($0.08)
Total Operating Expenses ($USD)	$27.69M	$21.95M	$23.72M
Cash & Cash Equivalents ($USD)	$157.69M	$139.04M	$116.59M

Note: Asterisks indicate values retrieved from S&P Global.*

Operating Expense Mix (oldest → newest)

Metric	Q3 2024	Q4 2024	Q1 2025
R&D Expenses ($USD)	$14.95M	$17.93M*	$15.57M
G&A Expenses ($USD)	$7.90M	$6.63M*	$8.16M
Deferred Revenue ($USD)	$11.80M	$9.77M	$7.47M

Note: Asterisks indicate values retrieved from S&P Global.*

Q1 2025 vs S&P Global Consensus

Metric	Actual	Consensus	Surprise
Revenue ($USD)	$2.30M	$1.35M*	+$0.95M; +71%
EPS ($)	($0.08)	($0.09)*	+$0.01

Note: Consensus values retrieved from S&P Global.*

Context:

YoY: Revenue down ($2.30M vs $3.41M in Q1’24), net loss improved ($21.53M vs $24.06M), reflecting lower R&D vs prior-year GMP/commercial process activities and higher G&A from compensation and legal/professional fees .
QoQ: Revenue up modestly vs Q4’24; OpEx rose as programs approach pivotal; cash decreased as operations continued without product revenues .

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Cash runway	Multi-year	“Into the fourth quarter of 2026” (FY 2024 PR)	“Into the fourth quarter of 2026” (Q1 PR)	Maintained
Pivotal Part B – Regulatory path	2025	“Update on pivotal trial design expected in H1 2025”	Written FDA alignment on key elements; submit protocol/SAP as IND amendment in Q2 2025; no end-of-phase meeting	Clarified/Accelerated
Pivotal trial start	2025	Not specified	Pivotal initiation activities anticipated Q3 2025 (announced post-Q1 in Q2 PR)	New timing disclosed
Program update (design, natural history, clinical)	Q2 2025	H1 2025	Q2 2025 alongside IRSF meeting	Narrowed to event
Safety	Ongoing	Well tolerated (Part A ongoing)	No treatment-related SAEs/DLTs at both doses to date	Maintained

Earnings Call Themes & Trends

Topic	Previous Mentions (Q3 2024, Q4 2024)	Current Period (Q1 2025)	Trend
Regulatory path & endpoint	RMAT Type B; focus on objective functional measures; RSBQ excluded; CMC pivotal product approved	Written FDA alignment; objective, non–effort-based endpoint; blinded video raters; IND amendment replaces end-of-phase meeting	Accelerating/clarified
Safety/tolerability	High-dose generally well tolerated; IDMC cleared continued high-dose enrollment	No treatment-related SAEs/DLTs; confidence building with more high-dose patients dosed	Positive, consistent
Dose strategy (high vs low)	High-dose cohort expanding	Expect faster/more robust responses at high dose; translational support; likely preferred dose	Favoring high dose
Natural history dataset	Discussed to support single-arm design; analysis underway	Central to FDA alignment; upcoming detailed disclosure at IRSF	From preparatory → deployed
CMC readiness	Pivotal product released; commercial process endorsed	Reiterated readiness to support pivotal	Stable, supportive
Global/regulatory expansion	—	EMA groundwork; UK CTA active; potential EU expansion with capital	Laying foundation
Strategic partner (Astellas)	—	Pediatric data package triggers summer opt-in clock per agreement terms	Partner option approaching

Management Commentary

“We obtained written alignment from the FDA on key elements of our pivotal Part B trial design... FDA advised us to proceed directly to submitting our pivotal trial protocol and SAP as an amendment to the IND... eliminating the need for a formal end-of-phase meeting.” — Sean Nolan, CEO .
“It’s not effort-based. It is objective, and it’s very clinically meaningful... with mechanisms in place for bias mitigation... video assessments... appropriately blinded.” — Sean Nolan on the primary endpoint construct .
“Net loss... was $21.5M or $0.08 per share... we continue to expect that our current cash resources will support planned operating expenses and capital requirements into the fourth quarter of 2026.” — Kamran Alam, CFO .
“Rett requires an increase in MECP2... early clinical benefit is a strong indicator that MECP2 protein has reached therapeutic levels... outcomes seen thus far supported our ability to reach alignment with the FDA on key elements of the pivotal trial design.” — Sukumar Nagendran, President & Head of R&D .

Q&A Highlights

Dose response and bar for success: Management expects faster onset and greater magnitude at high dose assuming safety persists; primary endpoint agreed with FDA is objective, non–effort-based, and clinically meaningful; detailed criteria to be disclosed with protocol .
IND amendment and timeline: FDA alignment obviates end-of-phase meeting; submit protocol/SAP in Q2; 30-day clock with potential for rapid site initiation thereafter .
Design specifics: Single-arm approach with patients as their own control, robust bias mitigation (video assessments; blinded raters/adjudicators) .
Global/regulatory: UK sites active; EMA engagement advancing; EU/UK market comparable to U.S. in population size .
Immunosuppression regimen: Prednisone tapered over ~12 weeks; sirolimus taper ~24–25 weeks currently; may simplify in Part B given safety profile .

Estimates Context

Q1 2025 vs S&P Global consensus: Revenue $2.30M vs $1.35M consensus (beat), EPS ($0.08) vs ($0.09) consensus (beat) [*S&P Global].
Implications: The magnitude of the revenue beat (deferred/collaboration-driven) and smaller EPS loss may prompt modest upward revisions to near-term OpEx efficiency assumptions; however, TSHA remains pre-revenue with results driven by collaboration accounting, not product sales.
Forward estimates likely hinge more on pivotal initiation timing (Q3 2025 anticipated) and clarity of the primary endpoint/regulatory path than on quarterly revenue cadence .

Note: Consensus figures are retrieved from S&P Global.*

Key Takeaways for Investors

Regulatory de-risking: Written FDA alignment and IND amendment pathway remove a key gating item, potentially accelerating pivotal initiation to Q3 2025 .
Clinical de-risking: Clean safety to date across dosing cohorts and ages, with early, durable functional gains supporting an objective, clinically meaningful primary endpoint .
Execution catalysts: IRSF program update (Q2 2025), IND amendment filing (Q2), and pivotal start (Q3) serve as material stock catalysts in 2025 .
Competitive positioning: Intrathecal, self-complementary construct and objective, bias-mitigated endpoint strategy may offer differentiation; management expects high dose to drive faster, deeper responses .
Cash runway into Q4 2026 provides line-of-sight to pivotal initiation and interim analyses, though eventual commercialization/regulatory work will require continued capital market access .
Partner optionality: Astellas pediatric data package could trigger opt-in timing this summer, adding potential strategic/financial upside .
Watch list: Detailed endpoint definitions, Site activation pace, and EMA/U.K. expansion steps; any safety signal emergence remains the principal risk in gene therapy development .

Sources:

Q1 2025 press release and financials .
Q1 2025 Form 8-K (Item 2.02; Exhibit 99.1) .
Q1 2025 earnings call transcript (prepared remarks & Q&A) -.
FY 2024 press release (context/prior quarter) -; Q4 2024 call -.
Q3 2024 press release and call (trend analysis) - -.
Pivotal Part B trial design & Part A data (May 28, 2025) -.

Asterisks indicate values retrieved from S&P Global.*

Taysha Gene Therapies, Inc. (TSHA)·Q1 2025 Earnings Summary