GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - UNIQURE NV

Financial Performance:

• No specific financial metrics (revenue, earnings, margins, cash flow, or debt) were disclosed as the company is in the clinical development phase prior to commercialization.
• The transcript focuses entirely on clinical trial progress, regulatory strategy, and operational readiness rather than financial reporting.

Guidance and Future Outlook:

• Regulatory Timeline: Awaiting FDA Advisory Committee (AdCom) decision; PDUFA date (May 1st) is the target for completing enrollment and demonstrating progress to the FDA.
• Confirmatory Study: Launching a 200-patient, sham-controlled, double-blinded study with a 36-month endpoint; enrollment is prioritized as the "number one clinical priority."
• Commercial Launch: Anticipates product availability around the middle of the following year if approved, with a strategy to prioritize existing HD treatment center patients over newly diagnosed individuals initially.
• Global Expansion: Plans to emphasize international enrollment for the confirmatory study post-approval due to the lack of alternative treatments and clear regulatory pathways outside the US.

Business Segments and Product Lines:

• Core Asset: AMT-130, a gene therapy for Huntington's disease (HD), targeting the largest unmet need in the genetically defined rare disease space.
• Clinical Data: 51 patients treated in the Phase 1-2 program across two dose cohorts; high-dose patients showed durability of effect out to 48 months.
• Endpoints: Total Functional Capacity (TFC) is identified as the robust primary clinical measure and primary endpoint for the confirmatory study; UHDRS showed a stable trend over 48 months despite annual variability in the CUHDRS sub-component.
• Operational Infrastructure: Identified approximately 100 sites in the US equipped with ClearPoint MRI-guided stereotactic systems, with ~60 recognized as HD Centers of Excellence capable of administration.

Market and Competitive Landscape:

• Market Need: Describes HD as a "ferociously devastating disease" with a patient community highly motivated to accept risks for transformational therapy.
• Competition: No commercially available treatments exist for HD currently, creating an environment of high patient enthusiasm and demand for AMT-130.
• Patient Engagement: The Huntington's disease community is vocal; management expects the patient voice to be represented at FDA AdComs to emphasize risk-benefit perceptions.

Risks and Challenges:

• Regulatory Uncertainty: Market sentiment is heavily focused on regulatory risk regarding the BLA submission and the shift from the original to the EnrollHDA dataset.
• Screening Failure: Historically experienced a 50-60% screening failure rate for the study, driven by the need for specific volumetric MRI assessments.
• Site Infrastructure: Potential hurdle regarding the availability of ClearPoint apparatus and volumetric MRI capabilities at all sites, though management expects this to be manageable with existing infrastructure.
• Data Interpretation: Risk of over-interpreting short-term variability in the CUHDRS sub-component, necessitating a focus on longer-term TFC trends.

Management Commentary and Tone:

• Confidence Level: Management expressed strong confidence in the scientific validity of switching to the EnrollHDA dataset, citing it as the most contemporaneous and comprehensive data available.
• Tone: Defensive yet optimistic regarding regulatory hurdles; emphasized the durability of clinical effects and the critical nature of the unmet need.
• Strategic Focus: Reiterated commitment to expeditious execution of the confirmatory study to satisfy FDA requirements for post-approval safety monitoring.

Analyst Questions and Answers:

• Q: Rationale for switching to EnrollHDA?
  • A: Scientifically necessary to use the most recent data (Sept 2025, 25,000+ participants) for better contemporaneity with the clinical trial; FDA was expected to prioritize this "clean" pre-specified analysis.
• Q: TFC vs. CUHDRS discrepancy?
  • A: TFC is the most critical, stable, and "rock solid" metric (0.1 point loss/year for treated vs. >1 point for untreated); CUHDRS variability is expected due to its performance-based nature and is less predictive of long-term functional decline than TFC.
• Q: Patient enrollment in the confirmatory study?
  • A: High enthusiasm expected; randomization ensures patients receive treatment (either drug or open-label) if the investigator deems it safe; no specific enrollment number mandated by FDA, but "plethora" of sites and patients in screening are being mobilized.
• Q: MHRA regulatory path compared to FDA?
  • A: MHRA process is longer (3+ months beyond FDA) and lacks a fixed PDUFA date, utilizing "clock stops" for question resolution rather than a single deadline.
• Q: Commercial launch volume and site capacity?
  • A: Site throughput will vary (1/month to 1/week); ClearPoint availability is not a primary bottleneck given ~100 equipped sites exist; volume MRI requirement can be managed through site partnerships.

Other Key Points:

• The BLA submission is based on the January 2023 EnrollHD data cut presented in September 2025, which included ~19,000 participants.
• Management clarified that the FDA recommended a sham-controlled double-blinded study due to previous concerns about lack of pre-specification in earlier analyses.
• The company is committed to ensuring volumetric MRI availability for all approved treatment centers if mandated by the label.
• The confirmatory study is viewed not just as a regulatory requirement but as a pathway for patients to access treatment immediately if they cannot wait for commercial launch.