STIFEL 2026 HEALTHCARE CONFERENCE - UNIQURE NV

Explicit Guidance:

• Financial Runway: Management expects the current cash position of approximately $780 million to provide sufficient runway to advance non-HD programs and prepare for commercial launch, extending into 2030.
• Revenue/Earnings: No specific quantitative revenue, earnings, or margin guidance provided.
• Capex/Opex: No specific capital expenditure or operating expense guidance provided.

Business-Segment Outlook:

• Lead Program (AMT-130/Huntington's):
  • 2027 Focus: Management explicitly stated a goal to make 2027 "our best year" and a "very impactful year" for Huntington's patients.
  • Regulatory Milestone: BLA for AMT-130 has been accepted with Priority Review; a Panel (Adcom) is expected as part of the standard process for a first-in-class gene therapy.
  • Confirmatory Study Design: A global, randomized, non-blinded confirmatory study (treatment vs. standard of care) targeting Total Functional Capacity (TFC) is expected to reach 36 months of follow-up.
    • Enrollment Target: Approximately 200 patients total.
    • Timeline: Study design finalized recently; management expects significant enrollment progress and site activations to be "meaningfully underway" by the PDUFA date (Spring 2027) to support the accelerated approval criteria.
    • Geography: Initial focus on the US, with parallel site activation internationally for post-approval recruitment.
  • Commercial Launch (US):
    • Distribution Capacity: Targeting a network of 15 to 30 high-throughput sites (intersection of ~100 ClearPoint catheter-certified sites and 60 HD Centers of Excellence) capable of performing precision-targeted surgical delivery.
    • Team: Commercial team (medical, field, strategic accounts) is currently being built and is expected to be ready for launch execution.
    • Indication: Likely focuses on early manifest patients (Stage 2 or 3), consistent with the Phase 1/2 study population.
  • UK Market:
    • Regulatory Status: Second license application under review by the MHRA (validated recently).
    • Market Size: ~7,000–8,000 diagnosed patients and 35,000–40,000 pre-symptomatic patients.
    • Strategy: Plans to utilize a distributor model.
    • Pricing/Access: Parallel discussions with NICE expected; potential eligibility for the Innovative Medicines Fund within six months of UK approval.

Market and Competitive Outlook:

• Demand vs. Supply: Demand is viewed as "not going to be much of an issue" due to the "tremendous unmet need" and lack of disease-modifying treatments.
• Primary Constraint: The "supply side" (surgical capacity and specialized centers) is the primary commercial bottleneck to be addressed pre-launch.
• Competitive Landscape: AMT-130 is positioned as the first-ever disease-modifying, one-time administered gene therapy for Huntington's disease.

Macro / Industry Outlook:

• Regulatory Environment: Management describes the current FDA leadership interaction as "constructive and collaborative," contrasting with prior tone under previous leadership.
• Data Standard: The company acknowledges the "well-understood" limitations of natural history controls in neurodegenerative studies (e.g., patient dropout bias over time) but asserts that the 48-month durability of the effect (slowing disease progression by 44% on TFC, 60% on clinical scores) remains compelling regardless of these modeling caveats.

Strategic Initiatives:

• Pipeline Expansion:
  • Temporal Lobe Epilepsy: Phase 1/2 dose-ranging study with 13 patients; additional data expected in the first half of next year (12-month follow-up on first dose, 6-month on second).
  • Fabry Disease: Leveraging existing hemophilia B expertise (Hemgenix); Phase 1/2 dose-ranging study in three cohorts; additional data expected in the first half of next year (4 to 18 months follow-up).
• Commercial Build-out: Active hiring and structuring of a dedicated commercial team for AMT-130 launch readiness.

Risks and Headwinds to Outlook:

• Regulatory Risk: The FDA Adcom may "stress test" or "torture" the external control data; potential questions regarding the sensitivity analysis and the robustness of the natural history comparator remain a risk to accelerated approval.
• Study Execution Risk: Accelerated approval is conditional on the confirmatory study demonstrating meaningful progress by the PDUFA date; failure to meet enrollment benchmarks could jeopardize approval or necessitate delays.
• Data Limitations: The external control dataset suffers from increasing data point loss and patient dropout bias after 48 months, which management acknowledges as a known limitation that compounds over time, potentially impacting long-term statistical interpretations.
• Surgical Capacity: Success depends on the ability to recruit and activate sufficient specialized sites (neurosurgeons with interoperative capabilities) to meet patient demand.

Management Tone on the Future:

• Confidence Level: High confidence in the data's ability to support approval ("we believe the drug is approvable," "data continues to be supportive").
• Commitment: Described as "100% committed" to executing the confirmatory study and advancing the program.
• Perspective: Management dismisses skepticism regarding short-term data variance, emphasizing the clinical significance of slowing disease progression in a fatal, untreatable condition. They anticipate a positive outcome from the Adcom and prioritize patient impact.

Miscellaneous:

• Timeline: 2027 identified as the pivotal year for launch and impact.
• PDUFA Date: Anticipated to be in Spring 2027.