GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - UNIQURE NV

Explicit Guidance:

• No financial guidance (revenue, earnings, margins, capex, or operating metrics) provided for any period.

Business-Segment Outlook:

• Confirmatory Study (200-patient): Enrollment to proceed expeditiously with inclusion criteria nearly identical to Phase 1-2; study design includes built-in statistical margins for a 36-month Total Functional Capacity (TFC) endpoint.
• Target Population: CEO estimates up to 30% of patients under care at leading centers may be eligible based on striatal volume criteria, pending final labeling; screen failure rate anticipated at 50–60%.
• Launch & Commercialization: Anticipates product availability ("middle of the year" assumption); high patient demand expected in the US and significant emphasis on non-US enrollment post-approval due to lack of alternative treatments and standard of care in those regions.
• Treatment Capacity: Identifying ~60 HD Centers of Excellence with ClearPoint apparatus; expects ~100 US sites total possess the necessary equipment; throughput at individual sites expected to increase over time.

Market and Competitive Outlook:

• Demand: Describes the unmet need in genetically defined Huntington's disease (HD) as "one of the largest" with "ferociously devastating" patient impact; predicts extraordinary patient enthusiasm and lack of competing treatment options.
• Market Positioning: Aims to be successful in both product launch and long-term market presence; expects patients to accept risk-benefit profiles of transformational medicines.
• Advisory Committee: Anticipates patient voice representation at FDA Advisory Committee meetings (if convened) to reflect community sentiment and risk perception.

Macro / Industry Outlook:

• Regulatory (FDA): FDA will review the BLA submission based on the "EnrollHDA cut" data (January 2023 data from CHDI, updated Sept 2025); FDA previously recommended a sham-controlled, double-blinded study to address pre-specification concerns.
• Regulatory (MHRA): UK MHRA process expected to take "three-plus months more than the FDA process" due to lack of a fixed PDUFA date and potential clock stops for question response.
• Competitive Landscape: Emphasizes the absence of commercially available treatments for HD currently, with no alternatives expected "anytime soon" outside the US.

Strategic Initiatives:

• Site Expansion: Commitment to open a "plethora" of sites to demonstrate to the FDA that post-approval study completion will be timely; focused on sites with highest volume throughput capability in Year 1.
• Data Strategy: Utilized the most contemporaneous natural history data (EnrollHDA cut) from CHDI for analysis to ensure scientific robustness and alignment with FDA expectations regarding pre-specification.
• Study Execution: 51 patients already enrolled in Phase 1-2; proceeding with confirmatory study design to demonstrate interpretable results over a 36-month horizon.

Risks and Headwinds to Outlook:

• Regulatory Risk: Primary concern for the market is potential regulatory hurdles or refusal of approval despite clinical data; outcome of FDA Advisory Committee is not guaranteed.
• Operational Execution: Potential screen failure rates of 50–60% and variability in site efficiency throughput (1 procedure/month vs. 1/week); reliance on ClearPoint availability and MRI volumetric assessment capabilities at treatment centers.
• Data Interpretation: Potential for over-interpretation of year-over-year fluctuations in composite UHDRS measures; variability in performance-based tests versus the more stable Total Functional Capacity (TFC).
• Commercial Rollout: Delay in treatment access post-launch due to prioritization of existing patients; logistical challenges in expanding treatment centers to meet demand.

Management Tone on the Future:

• Confidence: High confidence in the scientific validity of the EnrollHDA cut decision and the durability of clinical effects (TFC remaining "rock solid" with <0.1 point loss/year in high-dose group through 48 months).
• Commitment: "100% committed" to expeditious execution of the confirmatory study; proactive in addressing FDA concerns regarding pre-specification and data cleanliness.
• Optimism: Views the current market focus on regulatory risk as a "disconnect" from the actual commercial opportunity and patient need; expects high demand and successful long-term adoption.

Miscellaneous:

• Timeline References: Data presented in September 2025 (EnrollHD update); PDUFA date referenced as May 1st (implied 2026 context); Confirmatory study endpoint at 36 months.
• Clinical Metrics: High-dose AMT-130 showed >1 point favorable composite UHDRS vs. low-dose at 48 months; untreated patients lose >1 point/year in TFC vs. <0.1 point/year for treated patients.
• Geography: Distinction made between US (high demand, existing standards of care) and non-US (zero commercial availability, prioritized enrollment source).