uniQure N.V. Study update

This morning, uniQure announced additional data on patients treated with our investigational gene therapy, ifezuntirgene inilparvovec, or AMT-130, in our ongoing phase I/II clinical trials in Huntington's disease, taking place in the U.S., E.U., and the U.K. This update consists of data on clinical endpoints, an exploratory biomarker, and safety and tolerability. Joining us for this investor event and webcast are Matt Kapusta, our Chief Executive Officer, Dr. Walid Abi-Saab, our Chief Medical Officer, and to provide a clinician's perspective on the experience of patients with Huntington's disease, Dr. Victor Sung, Professor of Neurology at the University of Alabama at Birmingham, UAB, Director of the UAB Huntington's Disease Clinic, and a clinical investigator in this trial of AMT-130. Kylie O'Keefe, our Chief Commercial and Strategy Officer, will be joining us for the analyst Q&A at the end of this presentation.

The slides included in this morning's webcast have been filed with the SEC and will be available on the Events and Presentations page of uniQure's website shortly after the conclusion of this webcast. Please note that we will be making forward-looking statements during this investor call. All statements other than statements of historical fact are forward-looking statements. They are based on management's beliefs and assumptions and on information available to management only as of the date of this webcast. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the factors described in uniQure's quarterly report on Form 10-Q, filed on July 29, 2026, and other security filings. Given these risks, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these statements, even as new information becomes available in the future.

Now, I am pleased to introduce Matt Kapusta, uniQure's CEO.

Thanks, Chiara, and good morning, everyone. Thank you for joining us on today's call. This morning, we announced additional data from our ongoing studies of AMT-130 in Huntington's disease. These results continue to provide evidence of long-term, meaningful slowing of disease progression and support the primary analysis underpinning the license applications we submitted to the FDA and MHRA. To date, no other program in Huntington's disease has demonstrated long-term disease modification after a single administration. AMT-130 does. As pioneers in this space, we are blazing a new trail in HD, learning and deepening our understanding with every data point we generate. At 48 months, we continue to see meaningful treatment effects. Huntington's disease is relentless and progressive. There is nothing available today that changes its course. Our aim now is to bring forward the first disease-modifying treatment for people living with Huntington's.

The data we announced this morning include analyses at two time points. The first is a 48-month analysis based on the first 12 high-dose patients that have reached this time point. The second is a 36-month analysis reflecting all 15 patients, including three additional patients who have reached that time point since last year's update. Starting with the 48-month data, we continue to see treatment benefit across both cUHDRS and Total Functional Capacity, or TFC, with particularly significant effect on TFC demonstrating a 61% slowing of disease progression and stable treatment benefit at 48 months. TFC is the most direct measure we have of what patients and families care about. It captures whether someone can hold a job, manage their own finances, and perform the daily tasks that allow them to live independently. It is also the agreed-upon primary endpoint of our confirmatory study.

While the primary cUHDRS analysis did not reach statistical significance in 48 months, we believe the trends are positive and meaningful for HD patients. HD patients' lives are defined by moments, and a year of meaningful moments is something no patient should have to give up. There is also an important limitation in the new updated external control. 53% of the external control data is missing at 48 months. While missing this is inherent to long-term natural history datasets, the patients who left the control were declining markedly faster than those who remained. So over time, the comparator increasingly reflected a healthier population than at baseline. This bias cuts against AMT-130, not for it. It understates treatment benefit and makes statistical comparisons at the 40-month time point more difficult.

As we advance as leaders in HD, we will continue our collaboration with key stakeholders to assess the most meaningful ways to evaluate long-term treatment benefit. When comparing cUHDRS at 48 months across doses, we do see clear dose dependencies, with the high dose showing a one-point favorable effect on cUHDRS compared to the low dose. Importantly, this is an internal comparison that does not depend on the control and is what you would expect to see if there was a genuine treatment effect. Turning to the updated 36-month data, this is an important time point from a regulatory perspective, as it's consistent with the BLA primary analysis in our planned confirmatory study. Including the three additional patients, the 36-month data demonstrate an even stronger treatment effect. We now see 80% slowing of disease progression on cUHDRS, 67% slowing on TFC, and favorable trends across all other clinical sub-domains.

As a reminder, the three additional patients at 36 months are not included in the 48-month analysis. In summary, we strongly believe AMT-130 has the potential to deliver meaningful long-term benefit to people living with Huntington's disease, and we will continue to work tirelessly to deliver this treatment option to them. Patients and loved ones waited long enough for a therapy that changes what this disease does to them. We firmly believe AMT-130 is that treatment. As we move forward, we remain laser focused in the near term on three areas. First, continued engagement with the FDA and MHRA as their reviews advance. Second, timely execution of our confirmatory study targeting initiation of patient screening before the end of this year. Third, advancing our commercial preparations so that we are ready to deliver this therapy if and when approved.

With that, let me hand it over to Walid to walk you through the data in more detail.

Walid? Thank you, Matt. Good morning, everyone.

Before I go over to the updated analyses, let me set the stage by reviewing the 36 months analysis from last year. This is the study design and statistical analysis plan supporting our recent regulatory submissions to the FDA and MHRA. Our primary endpoint is the Composite Unified Huntington's Disease Rating Scale, or cUHDRS. We compare change from baseline at 36 months against an external natural history cohort, ENROLL-HD, using a propensity score methodology. At the time of last year's analysis, which we presented to you in September of 2025, 12 patients on the high dose had reached 36 months of follow-up as of the data cutoff of June 30, 2025. The main takeaway from this analysis was that AMT-130 high dose showed a statistically significant slowing of disease progression at 36 months.

75% slowing on cUHDRS and 60% slowing on Total Functional Capacity, or TFC. I draw your attention to the decline of the matched natural history cohort after three years. These correspond to an average decline of half a point per year on cUHDRS and 0.3 points per year on TFC. I will come back to these numbers later in my presentation. Today, we are updating you with the results of the analyses based on the data from the June 30, 2026 study data cutoff. 12 patients have now reached 48 months on the high dose, and 12 patients have reached 48 months on the low dose. In addition, three more patients have reached 36 months on the high dose, making the 36-month time point fully representative of all enrolled patients at the high dose, factoring in the two patients who dropped out at 12 and 15 months.

There is an important comparative update that I would like to explain to assist in understanding the interpretation of both the 36-month and the 48-month data. The 48-month protocol and statistical analysis plan, which we submitted earlier this year, pre-specified the most current ENROLL-HD dataset released in September of 2025. We will refer to this as ENROLL-HD B throughout this presentation. Last year's 36-month analysis used the January 2023 released dataset, which we will call ENROLL-HD A. ENROLL-HD B contains everything in ENROLL-HD A, plus more than 2 and a half years of additional follow-up on those same participants and 6,000 additional ones. It is the largest and most contemporaneous longitudinal natural history database available. It also overlaps in time with recruitment and follow-up of High Dose Cohort 2 in our phase I/II studies. Contemporaneous controls are an FDA preference, and that was a significant factor in the choice.