Executive Summary

Q3 revenue of $3.7M increased by $1.4M y/y on higher license revenue, but operating loss widened and non-operating expense surged, driving a net loss of $80.5M ($1.38/share) versus a $44.4M loss ($0.91/share) in Q3’24 .
Management disclosed a key regulatory setback: preliminary FDA pre-BLA feedback indicates external-control Phase I/II data for AMT-130 may not be adequate as primary BLA evidence, rendering BLA timing unclear; the company plans urgent FDA engagement .
Balance sheet was fortified by an upsized follow-on (net proceeds ≈$323.7M) and debt refinancing, ending Q3 with $694.2M in cash, cash equivalents and current investment securities, extending cash runway into 2029 .
Key pipeline milestones: AMT-130 high-dose showed statistically significant 75% slowing on cUHDRS and 60% on TFC at 36 months; AMT-260 Phase I/IIa cohort enrollment advanced; AMT-191 initial Phase I/IIa data showed 27–208x α-Gal A increases and ERT withdrawal; AMT-162 enrollment paused after a DLT-related SAE in one patient .
Stock reaction catalyst: the FDA stance shift on AMT-130’s evidentiary approach and any follow-on FDA minutes/next steps disclosed by management are likely to dominate near-term narrative and positioning .

What Went Well and What Went Wrong

What Went Well

AMT-130 achieved statistically significant efficacy at 36 months: 75% slowing of disease progression on cUHDRS (p=0.003) and 60% on TFC (p=0.033); NfL −8.2% at 36 months; safety generally manageable with no new drug-related SAEs since December 2022 .
Strengthened liquidity and runway: ~$323.7M net offering proceeds (gross ~$345M) and debt refinancing increased cash and investments to $694.2M at quarter-end; runway now into 2029 .
Management conviction and commercialization readiness: “The third quarter… marked a defining moment… AMT-130… demonstrated statistically significant slowing of disease progression,” while continuing commercial planning in U.S. and exploring EU/UK pathways .

What Went Wrong

Regulatory surprise: FDA preliminary pre-BLA feedback no longer supports using Phase I/II external-control data as primary BLA evidence; BLA timing now unclear, a shift from prior 2024–H1’25 alignments .
Financials deteriorated: Non-operating items swung to a $20.9M expense (FX headwinds, warrant liability FV change, issuance costs), contributing to a wider net loss of $80.5M in Q3 .
Pipeline hiccup: AMT-162 (SOD1 ALS) enrollment paused following a dose-limiting toxicity leading to a related SAE in one patient; continued data collection underway .

Financial Results

Quarterly P&L trend (oldest → newest)

Metric (USD)	Q1 2025	Q2 2025	Q3 2025
Total revenues	$1.567M	$5.262M	$3.701M
Research & development	$(36.140)M	$(35.383)M	$(34.366)M
SG&A	$(10.908)M	$(13.500)M	$(19.438)M
Total operating expenses	$(47.245)M	$(49.539)M	$(54.202)M
Loss from operations	$(39.331)M	$(43.865)M	$(51.035)M
Non-operating items, net	$(3.810)M	$6.571M	$(20.868)M
Net loss	$(43.637)M	$(37.719)M	$(80.529)M
Basic & diluted EPS	$(0.82)	$(0.69)	$(1.38)

Year-over-Year snapshot (Q3 2025 vs Q3 2024)

Metric (USD)	Q3 2025	Q3 2024
Total revenues	$3.701M	$2.287M
Net loss	$(80.529)M	$(44.378)M
Basic & diluted EPS	$(1.38)	$(0.91)

Liquidity (balance sheet items, period-end)

Metric (USD)	Q1 2025 (3/31)	Q2 2025 (6/30)	Q3 2025 (9/30)
Cash & cash equivalents	$217.229M	$253.778M	$597.056M
Current investment securities	$191.782M	$123.196M	$97.189M
Cash runway commentary	Into 2H’27	Into 2H’27	Into 2029

Note: CFO prepared remarks referenced $649.2M in “cash, cash equivalents, and investment securities,” but the 8-K/press release and balance sheet show $694.2M ($597.056M cash + $97.189M current investments) as of 9/30/25 .

Q3 2025 Actual vs Wall Street Consensus (S&P Global)

Metric	Actual	Consensus	Surprise
Revenue	$3.701M	$5.269M*	Miss
EPS (Primary)	$(1.38)	$(0.88)*	Miss
EBITDA	$(45.58)M*	$(40.29)M*	Miss

Values marked with * retrieved from S&P Global.

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
AMT-130 BLA submission	Regulatory timeline	Plan to submit BLA in Q1’26 with SAP/CMC alignment	Timing unclear after FDA pre-BLA feedback; urgent engagement planned	Lowered/Delayed
Cash runway	Multi-year	Fund ops into 2H’27	Fund ops into 2029	Raised runway
AMT-260 data update	Clinical timing	Early patient data shared; sites screening	Additional clinical data expected 1H’26	Maintained timing
AMT-191 data update	Clinical timing	Initial data 2H’25 planned	Updated data expected 1H’26	Pushed to 1H’26
AMT-130 Cohort 4 dosing	Operational	Cohort 4 planned	Initiated and fully recruited; dosing to complete by YE’25	Progressed

Earnings Call Themes & Trends

Topic	Previous Mentions (Q1–Q2 2025)	Current Period (Q3 2025)	Trend
AMT-130 regulatory path	FDA Breakthrough; alignment on SAP/CMC; BLA planned Q1’26	FDA pre-BLA feedback no longer supports external-control data as primary BLA evidence; timing unclear	Negative shift
AMT-130 efficacy	Anticipated 3-yr topline in Sept	75% slowing (cUHDRS), 60% (TFC), NfL −8.2%; generally well-tolerated	Strong positive data
AMT-260 (MTLE)	Early signals; 92% seizure reduction in first patient at 5 months; site activation	Enrollment advanced; more data 1H’26	Steady progress
AMT-191 (Fabry)	Initial data expected 2H’25	Initial data: 27–208x α-Gal A; ERT withdrawal; more data 1H’26	Positive data; timeline to 1H’26
AMT-162 (SOD1 ALS)	Enrollment continued; initial data 1H’26	Enrollment paused after DLT-related SAE at mid dose; continue data collection	Negative safety signal
Commercial readiness	Building plans for potential AMT-130 launch	Continued U.S. planning; exploring EU/UK; stakeholder engagement	Ongoing
Financial runway	Into 2H’27	Into 2029 post financing/refi	Improved

Management Commentary

“The third quarter of 2025 marked a defining moment… topline three-year data of AMT-130… demonstrated statistically significant slowing of disease progression… While the recent FDA feedback was unexpected… we strongly believe that AMT-130 has the potential to bring substantial benefit…” — CEO Matt Kapusta .
“We continue to believe that AMT-130 represents the most compelling therapeutic data set generated in Huntington’s disease to date… results were very consistent across sensitivity analyses…” — CMO Walid Abi‑Saab .
“Cash, cash equivalents, and investment securities totaled $649.2M… with this strong balance sheet, we… expect… sufficient to fund operations into 2029.” — CFO (note discrepancy vs 8-K/PR $694.2M) .

Q&A Highlights

External control robustness: CMO detailed rigorous propensity-score matching and multiple sensitivity analyses (including weighting, regional differences, comorbidities), with consistent results supporting robustness of AMT‑130 data .
FDA stance shift and prior alignment: CEO confirmed November 2024 written FDA comments supported external-control primary basis and cUHDRS as acceptable intermediate endpoint, contrasting with current pre‑BLA feedback; awaiting minutes to address concerns .
AMT-162 safety: Intrathecal route; observed dorsal root ganglia toxicity at mid dose (~3x low dose); different capsid vs other programs; next steps pending IDMC/expert discussions .
Community momentum: Strong patient/physician motivation post-data; disappointment at FDA feedback but ongoing collaboration to move forward .
Ex-US regulatory: No EMA/MHRA feedback yet; plans to engage in parallel with FDA process .

Estimates Context

Q3 2025 results missed consensus on revenue ($3.7M vs $5.3M*) and EPS (−$1.38 vs −$0.88*); EBITDA loss larger than expected (−$45.6M* vs −$40.3M*). Coverage counts: Revenue (11 ests), EPS (9 ests). Target Price Consensus Mean: $58.27* .
Values marked with * retrieved from S&P Global.

KPIs (Clinical)

KPI	Q3 2025 Detail
AMT-130 cUHDRS effect	75% slowing of disease progression at 36 months vs matched external control (p=0.003)
AMT-130 TFC effect	60% slowing at 36 months (p=0.033)
AMT-130 biomarker	CSF NfL −8.2% at 36 months (high-dose)
AMT-191 Fabry	27–208x α‑Gal A vs mean normal; all 4 Cohort A patients off ERT; stable lyso‑Gb3 through cutoff
AMT-260 MTLE	Enrollment advanced; data update expected 1H’26

Key Takeaways for Investors

AMT-130 efficacy is compelling with statistically significant slowing on two clinical endpoints, but the FDA’s preliminary stance on external-control primary evidence introduces material timing uncertainty; near-term narrative hinges on FDA minutes/next steps .
Q3 financials deteriorated primarily due to non-operating items (FX, warrant liability fair value, issuance costs), widening net loss; SG&A stepped up with commercialization preparation, while R&D trended slightly lower q/q .
Liquidity is a clear positive: post-offering/refi, QURE has $694.2M and runway into 2029, reducing financing overhang while it navigates regulatory pathways .
Pipeline breadth provides optionality: AMT-260 (epilepsy) and AMT-191 (Fabry) updates in 1H’26 can diversify catalysts; watch AMT-162 ALS safety update trajectory .
Trading setup: stock likely keys off regulatory updates (FDA minutes, any alignment on confirmatory/Phase 3 or alternative evidentiary strategy) and ex‑US regulatory engagement pace .
Estimate revisions: expect cuts to near-term EPS/EBITDA and pushout of AMT‑130 commercialization assumptions given BLA timing uncertainty; opex trajectory bears watching given commercialization spend .
Cross-check: note the call’s $649.2M cash figure vs 8-K/PR $694.2M; use 8-K/PR as authoritative for modeling .

Appendix: Additional Context

Financing: Sept 29, 2025 underwritten offering grossed ~$345M; net ≈$323.7M .
Q3 2025 YoY drivers: revenue up $1.4M (license), while non-operating expense increased by $16.7M (FX, warrant liability, issuance costs) .
Regulatory: Breakthrough Therapy designation (Apr 2025); prior alignment on cUHDRS intermediate endpoint; now FDA seeks different evidentiary approach; minutes pending .

uniQure N.V. (QURE)·Q3 2025 Earnings Summary