STIFEL 2026 HEALTHCARE CONFERENCE - UNIQURE NV

Financial Performance:

• No specific quarterly revenue, earnings, or margin figures were disclosed for the current reporting period.
• Cash Position: Approximately $780 million in cash on hand.
• Runway: Management estimates sufficient capital to fund launch preparation, advance other pipeline programs, and extend operations into 2030.

Guidance and Future Outlook:

• Primary Goal: 2027 is identified as the target year for a potentially impactful and "best year" performance regarding the Huntington's disease program.
• Regulatory Timeline: PDUFA date is set for May 1st; the BLA has been accepted with priority review status.
• Commercial Readiness: Planning is underway for a minimum of 15 high-throughput treatment centers in the U.S., with potential expansion to 20–30 sites.
• International Expansion: The UK Marketing Authorization Application (MAA) is under review by the MHRA; parallel discussions with NICE and potential access via the Innovative Medicines Fund are in motion.

Business Segments and Product Lines:

• AMT-130 (Huntington's Disease):
  • BLA Submission: Based on September 2025 data (36-month follow-up), utilizing the CUHDRS and Total Functional Capacity (TFC) as key endpoints.
  • Data Highlights: 48-month data shows patients retained total functional capacity (TFC) without loss (<0.1 points) compared to a full point loss in untreated cohorts; evidence of dose-dependency persists.
  • Confirmatory Study Design: A randomized, open-label (treatment vs. standard of care) global study involving ~200 patients is being initiated to support full approval; primary endpoint is TFC at 36 months.
  • Manufacturing/Supply: Delivery relies on the ClearPoint catheter system; target sites must possess functional neurosurgeons and interoperative capabilities.
• Temporal Lobe Epilepsy Program: 13 patients in a dose-ranging study; 12-month data for the first cohort and 6-month data for the second expected in H1 2026.
• Fabry Disease Program: Phase 1/2 dose-ranging study utilizing hemigenics expertise; data expected in H1 2026 (4–18 months follow-up).

Market and Competitive Landscape:

• Market Opportunity: ~30,000–40,000 symptomatic HD patients in the U.S. (estimates vary); UK market contains 7,000–8,000 diagnosed patients with 35,000–40,000 pre-symptomatic.
• Competitive Landscape: No other disease-modifying treatments are currently available for Huntington's disease, creating a significant unmet need.
• Market Dynamics: Demand is not expected to be a constraint; supply-side capacity (surgical centers) is the primary focus.

Risks and Challenges:

• Regulatory Scrutiny: Anticipated FDA Advisory Committee (AdCom) review to stress-test the use of external natural history controls (EnrollHD, Track-HD) rather than a sham-controlled arm.
• Data Limitations: Acknowledged challenges with external control datasets at 48 months due to missing data points and survivorship bias (healthier patients remaining in studies longer).
• Surgical Logistics: Dependence on a specialized network of certified centers (approx. 100 available, targeting 15–30 for launch) capable of precision-targeted gene therapy delivery.

Management Commentary and Tone:

• Confidence: Management expressed high confidence in the data's durability, the robustness of the statistical analysis, and the likelihood of accelerated approval.
• FDA Relations: Described the relationship as "constructive and collaborative"; noted a shift in FDA stance from June 2025 (Type B meeting) which approved the BLA submission based on existing data rather than a new sham-controlled trial.
• Patient Advocacy: Emphasized that the patient community urgently needs a treatment that slows disease progression by 44–60%.

Analyst Questions and Answers:

• AdCom Preparation: Management confirmed active preparation with mock panels and top advisory firms; acknowledged AdCom as a standard expectation for first-in-class disease-modifying therapies.
• External Control Validity: Explained that the comparator selection was based on the EnrollHD study (30,000+ participants, 10-year duration) and validated via sensitivity analyses against other datasets (Track-HD) and multiple covariates.
• FDA Leadership Changes: When asked about the impact of new FDA leadership, management declined to comment on specific personnel but affirmed the consistency of the regulatory interaction leading to the BLA acceptance.
• Confirmatory Study Enrollment: Expected to have multiple sites activated and patients enrolled by May 1st, though no specific enrollment number was mandated by the FDA.
• Labeling & Indication: While the trial focused on early manifest patients (Stage 2/3), specific labeling indications are yet to be finalized with the FDA.

Other Key Points:

• Regulatory Pathway: The BLA was accepted under the Real-Time Oncology Review (RMAT) designation framework discussions from 2024, facilitating the accelerated approval pathway.
• Data Consistency: Despite year-to-year fluctuations in CUHDRS scores (waxing and waning), management asserts long-term trends (comparing years 1–2 vs. 3–4) show consistent treatment effect.
• Pipeline Synergy: Fabry disease program leverages technical expertise from the approved Hemophilia B gene therapy (hemigenics).