[Management View]
Management reported a significant regulatory setback as the FDA no longer considers the Phase 1/2 external control data sufficient to support a BLA submission for AMT-130, introducing immediate uncertainty in the U.S. development timeline and strategy. Statistically significant efficacy was demonstrated for AMT-130 in Huntington's disease with both primary and secondary endpoints met, and biomarker data provided further clinical support. The AMT-191 and AMT-260 programs showed early clinical progress across Fabry disease and epilepsy, respectively, though updated data will not be available until next year.

[Outlook]
Management expects cash resources to be sufficient to fund operations into 2029. They plan to urgently engage with the FDA to discuss next steps for AMT-130 and expect to receive formal meeting minutes within the next 30 days. The company is also preparing for potential U.S. commercialization of AMT-130 and exploring regulatory engagement outside the U.S., including the EU and UK.

[Financial Performance]
Revenue for Q3 2025 was $3.7 million, up from $2.3 million in Q3 2024, driven by a $1.5 million increase in license revenues. R&D expenses increased by $3.8 million to $34.4 million, largely due to preparation for the AMT-130 BLA submission. SG&A expenses rose to $19.4 million from $11.6 million, mainly due to increased employee-related expenses and professional fees. Cash, cash equivalents, and investment securities totaled $649.2 million, up from $376.5 million at year-end 2024.

[Q&A Highlights]
Question 1: So the treatment effect you've reported out to three years is quite large. Could you remind us how you constructed the external control arm to consider whether there were any potential sources of bias?

Answer: We followed a rigorous propensity score matching process with enroll-HD, which provides a robust dataset due to its size. We conducted sensitivity testing using different types of matching and weighting, evaluated regional differences, comorbidities, and alternative statistical methods. Across these analyses, results were consistent, demonstrating robustness. The numerical change from baseline in our patient population was small compared to placebo or untreated subjects.

Question 2: Could you help us understand what happened in AMT-162, including the vector used and dose differences between cohorts?

Answer: We haven't disclosed all dose data, but we observed dorsal root ganglia toxicity at the middle dose, about threefold higher than the low dose. This is a known risk with this administration route. We are monitoring the data and will discuss next steps with the FDA and IDMC. This capsid is different from our other programs.

Question 3: Could you talk about what details you hope to learn from the final meeting minutes with the FDA?

Answer: We hope the minutes will reflect the conversation in Washington, D.C., and provide a sense of the FDA's concerns, outlining how to address them in subsequent meetings.

Question 4: Can you confirm prior meeting minutes documents supported accelerated approval based on CUHDRS?

Answer: Yes, in our November 2024 meeting, the FDA confirmed that Phase 1/2 data compared to an external control could serve as the primary basis for a BLA submission, and CUHDRS was acceptable for accelerated approval.

Question 5: What needs to happen to continue investing in Huntington's, and where do you draw the line between continuing versus giving up?

Answer: We are committed to collaborating with the FDA to expedite a BLA submission. We believe AMT-130 can benefit patients and have compelling data showing disease progression slowing. We will address concerns in a proper review and aim for an expeditious submission.

Question 6: For the ALS program, is it intrathecal delivery, and is the AE known to this route? How motivated is the Huntington's community?

Answer: Yes, it's intrathecal delivery, and dorsal root ganglia toxicity is known to this route. The Huntington's community is highly motivated, with a huge unmet need, working collaboratively to move the therapy forward.

Question 7: Have you received any EMA or MHRA feedback on accepting the external control dataset for AMT-130?

Answer: We haven't engaged with EMA or MHRA yet, prioritizing the FDA. We are committed to finding a path forward with all regulatory agencies.

Question 8: Given the dialogue with the FDA, did you ask why the path was no longer supportive of a BLA, and what data have you shared?

Answer: We can't comment on meeting details but hope for clarity from the minutes. The data shared with the FDA was consistent with publicly disclosed data, with additional sensitivity analyses not presented publicly.

[Sentiment Analysis]
The tone of management was determined and committed, focusing on addressing regulatory challenges and advancing their pipeline. Analysts expressed concern over regulatory setbacks but acknowledged the promising data and potential of AMT-130.

[Quarterly Comparison]
| Metric | Q3 2025 | Q3 2024 |
|---------------------------------|---------|---------|
| Revenue | $3.7M | $2.3M |
| R&D Expenses | $34.4M | $30.6M |
| SG&A Expenses | $19.4M | $11.6M |
| Cash Position | $649.2M | $376.5M |

[Risks and Concerns]
The FDA's shift in position regarding the sufficiency of Phase 1/2 data for AMT-130's BLA submission introduces uncertainty in the U.S. regulatory path. Enrollment in the AMT-162 ALS trial was paused due to dose-limiting toxicity, highlighting risks associated with intrathecal delivery.

[Final Takeaway]
uniQure faces significant regulatory challenges with the FDA's recent feedback on AMT-130, impacting its U.S. development strategy. Despite this, the company remains committed to advancing its pipeline, with promising data in Huntington's disease and other programs. Financially, uniQure is well-positioned with a strong cash balance to support operations into 2029. The company is focused on engaging with the FDA and other regulatory agencies to find a path forward for AMT-130, driven by the urgent need in the Huntington's community and the compelling clinical data supporting its potential.