uniQure N.V. Stock

Hello, and thank you for standing by. My name is John, and I will be your conference operator today. At this time, I would like to welcome everyone to the uniQure Third Quarter 2026 Earnings Call. [Operator Instructions]

I would now like to turn the call over to Chiara Russo, Senior Director of Investor Relations.

Thank you. Good morning and thank you for joining us for uniQure's third quarter of 2026 earnings call. Earlier this morning, uniQure released its financial results for the third quarter of 2026, and our press release is available on the Investors and Media section of our website at unicure.com. Our 10-Q was also filed with the SEC earlier today.

Joining me on the call this morning are Matt Kapusta, Chief Executive Officer; Dr. Walid Abi-Saab, Chief Medical Officer; Kylie O'Keefe, Chief Customer and Strategy Officer; and Christian Klemt, Chief Financial Officer. After our formal remarks, we'll open up for an analyst Q&A.

Before we begin, please note that we'll 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 conference call. 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 most recent SEC 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 if information becomes available in the future.

Now let me introduce Matt Kapusta, uniQure's CEO.

Good morning, and thank you for joining us on today's call. For the families who have waited generations for treatment for Huntington's disease, this quarter brought meaningful progress. As we announced on Monday, the FDA has accepted our biologics license application for AMT-130 and granted priority review with a target PDUFA date of May 1, 2027. In the United Kingdom, the MHRA has also validated our marketing authorization application.

These are the first such marketing applications for a disease-modifying therapy for Huntington's disease, and it brings patients and families one step closer to a treatment option. We greatly appreciate the engagement of both the FDA and the MHRA and their focus on the critical need for new therapies in Huntington's disease.

I also want to acknowledge the commitment of our clinical, regulatory and CMC teams who prepared and submitted both applications in record time. And to every HD patient, family member and investigator who has trusted us with their hope, thank you.

In September, we shared additional data from our ongoing Phase I/II studies, including updated 36-month data from all 27 evaluable patients across the low- and high-dose cohorts and for the first time, 48 months of follow-up after a single administration of AMT-130. These data continue to show meaningful dose-dependent slowing of disease progression and reinforce our strong belief that AMT-130 has the potential to deliver treatment benefit to patients.

We are also pleased to have aligned with the FDA on the key elements of the confirmatory study design, and we are making significant progress getting the trial up and running. We are fully committed to the timely execution of this study, and our priority is to have it well underway at the time of an approval decision. Walid will provide more detail on the confirmatory study later in the call.

Regarding commercial preparations, we are making excellent progress ahead of potential U.S. launch in 2027. We continue to build out our field, medical, market access and strategic account teams in a disciplined way and our financial strength provides the runway needed to execute this build-out. Kylie and Christian will provide more details on our commercial readiness and financial position later on the call.

Beyond AMT-130, we continue to advance our broader pipeline. We have completed enrollment in the second dose cohort of our Phase I/IIa study of AMT-260 in refractory mesial temporal lobe epilepsy and have resumed enrollment in the Phase I/II study of AMT-191 in Fabry disease. For both programs, we expect to present new and updated data in the first half of 2027.

In summary, we are heading into the end of 2026 with strong momentum. Our priorities are clear, working closely with regulators as the application reviews proceed, executing our confirmatory study, advancing our pipeline and building the organization to prepare for the planned launch of AMT-130.

With that, I will turn the call over to Walid to provide additional detail on AMT-130 and our pipeline. Walid?

Thank you, Matt. Good morning and good afternoon, everyone. I'll start with AMT-130 in Huntington's disease, or HD. As Matt noted, the BLA is under priority review with the PDUFA date of May 1, 2027, and the MAA has been validated by the MHRA. Both submissions are based on the 36-month analysis we presented in September 2025. In that analysis, the high dose of AMT-130 showed a 75% slowing of disease progression on the composite Unified Huntington's Disease Rating Scale, or cUHDRS, and a 60% slowing on total function capacity or TFC, compared with the propensity score matched external control. Both results were statistically significant.

With the BLA now accepted and under active review, going forward, we will not be commenting on specific information requests made by the FDA, including questions regarding a potential AdCom. The FDA indicated that they are tentatively planning to discuss our application at an AdCom. As you're aware, scheduling an AdCom is within the sole discretion of the agency.

In September 2026, we presented detailed analysis of a recent data cutoff. I will not repeat that today. Instead, I would like to focus on the progress we've made towards initiating the confirmatory study. Earlier this year, we reached alignment with the FDA on key elements of the design. Specifically, this will be a randomized study with a 2:1 ratio of AMT-130 high dose to standard of care. It will include approximately 200 patients. The primary endpoint is TFC at 36-month. After 36-month, all standard of care participants will be offered AMT-130 in a separate open-label study.

uniQure is fully committed to completing the study in a timely manner. Preparations started at the beginning of this year and have accelerated following alignment with the FDA. This will be a global study with sites across North America, Europe and Latin America. The protocol has already been submitted to institutional review boards or IRBs in the U.S., and we expect to begin patient screening by the end of this year.

I would like to take a moment to talk about TFC, the primary endpoint in the confirmatory study. This is a clinical endpoint that is very important, not only for regulators but also for people living with HD.

Why is TFC important? TFC captures whether a person can keep working, manage their finances, handle household responsibilities, take care of themselves day-to-day and live without full-time care. For patients and families, these are not abstract measures. They are the difference between maintaining and losing independence, and they are directly related to quality of life.

This is what patients and families care about. In fact, it is what we heard from HD specialists at the 2 most recent scientific meetings we attended, the International Parkinson and Movement Disorder Society meeting in Seoul and the European Huntington's Disease Network meeting in Krakow. These specialists describe TSC as the endpoint they find most meaningful when talking with patients.

Across our Phase I/II studies, TFC declined by less than 1/10 point per year in patients who received a high dose of AMT-130. This remarkably slow decline was consistent across all analyses and maintained through 4 years following treatment. Although these results come from a relatively small number of patients, they have never been seen before in HD.

Moving on to our other clinical programs, starting with AMT-260 for refractory mesial temporal lobe epilepsy. Following the initial 6-month data of the first low-dose cohort of 6 patients, which was presented in June, early in this quarter, we completed enrollment of the second cohort of 7 higher dose patients. We expect to present updated results from both cohorts in the Phase I/IIa study in the first half of 2027.

Turning to AMT-191 for Fabry disease. In August, enrollment resumed in the mid- and high-dose cohorts. As a reminder, dosing has been paused per protocol in these 2 cohorts after asymptomatic liver enzyme elevations, which fully resolved following a course of immunosuppression. We presented updated results in June from the March 15 cutoff, and we expect to share updated results from all 3 dosing cohorts in the first half of 2027.

Now I will turn the call over to Kylie to discuss our recent patient advocacy work. Kylie?

Thanks, Walid. With a known PDUFA date ahead of us, the question for our customer-facing team is no longer when. It's how. How do we make sure every piece of this patient journey is in place and well supported by the PDUFA date. So if approval is granted, we are ready to launch. For AMT-130, that journey runs from identifying an eligible patient through evaluation, surgery, follow-up and reimbursement. It involves many critical stakeholders.

Our job is to ensure a smooth process for patients, families and the clinicians who care for them. For many of these families, the patient journey already runs through a familiar place, a specialty HD clinic they have relied on for years. That is an important feature of this market as HD care is concentrated. A large share of diagnosed patients are seen at a number of specialty centers, many of them HDSA Centers of Excellence. That concentration will allow for a focused launch footprint.

We continue to see strong enthusiasm from the physician and patient community. This quarter, our team spent significant time with the Huntington's disease clinical and patient communities. That included the International Congress of Parkinson's Disease and Movement Disorders, or MDS, and the EHDN Clinical Research Congress. These meetings came shortly after we submitted our BLA and U.K. MAA and shared our recent data. That gave us a timely chance to hear directly from the physicians who care for HD patients every day.

Our ongoing interactions tell us that physicians and families place great weight on preserving function and independence. And that is why the total functional capacity data Walid described resonates so strongly. We expect uptake to be shaped mainly by treatment center capacity in the early launch period, not by demand. That's why center readiness is our top operational priority and preparing to allow them to be operational as quickly as possible after a potential approval.

Moving on to identifying treatment centers. AMT 130 is a one-time administered therapy through a neurosurgical procedure. Each treatment center, therefore, needs 3 capabilities working together. HD neurology expertise to identify and evaluate patients, neurosurgical teams experienced in image-guided delivery and the ancillary infrastructure to support the procedure and product handling.

We have identified priority centers in the U.S. and the U.K. Our readiness work at these centers covers 3 key areas: first, neurosurgical training and procedural support; second, product handling; and third, patient evaluation and referral pathways. Our goal is for a meaningful number of centers to be ready to treat eligible patients soon after a potential approval.

Finally, access and our ongoing work with payers. We have been engaging with access stakeholders through appropriate preapproval information exchange. These initial conversations cover the burden of Huntington's disease, the clinical data package and the economic profile of a onetime therapy. From early discussions, payers recognize the high unmet need in HD and the lack of any approved disease-modifying therapies. And there is a strong interest in learning more about AMT-130.

In the U.K., we have begun engaging with NICE NHS England and are planning for health technology assessments so that access can follow as closely as possible after any potential MHRA decision.

Finally, we continue to build the team that will make this launch a success. We expect to have our core team fully in place by early next year ahead of the PDUFA date. We're hiring with care, bringing in people with deep experience in rare disease gene therapy and neurology launches.

To summarize, we are preparing with urgency and discipline. Our goal is that if AMT-130 is approved, patients can move from referral to treatment as efficiently as possible.

With that, I'll turn the call over to Christian for a financial update. Christian?

Thank you, Kylie. I'll now be sharing the financial highlights of the third quarter of 2026. Please refer to the earnings press release issued this morning and our quarterly filings with the SEC for additional detail.

Revenue for the 3 months ended September 30, 2026, was $5.2 million compared to $3.7 million in the same period in 2025. The increase of $1.5 million is due to an increase in license revenue compared to the prior period.

Research and development expenses were $35.5 million for the 3 months ended September 30, 2026, compared to $34.4 million during the same period in 2025. The $1.1 million increase was primarily driven by $3.6 million increase in employee contractor-related expenses, including share-based compensation, which was partially offset by a $2.3 million decrease in direct research and development expenses. The decrease in direct research and development expenses resulted from a $4.1 million reduction in process validation expenses related to AMT-130, a $1.5 million increase in expenses related to AMT-260 and a $1.7 million increase in expenses related to preclinical activities and technology innovation projects.

Selling, general and administrative expenses were $23.9 million for the 3 months ended September 30, 2026, compared to $19.4 million during the same period 2025. The $4.5 million increase was primarily related to a $3 million increase in employee and contractor-related expenses, including share-based compensation, mainly as a result of the recruitment efforts over the last 12 to 15 months, a $0.7 million increase in professional fees and a $0.7 million increase in information technology costs to support the potential commercial launches of AMT-130.

Cash, cash equivalents and investment securities totaled $768.4 million as of September 30, 2026, compared to $622.5 million as of December 31, 2025. We believe that uniQure continues to be well positioned to execute on its clinical and operational priorities. We expect that cash, cash equivalents and investment securities will be sufficient to fund operations into 2030.

I'll now turn the call back over to Matt.

Thank you, Christian. As you've heard today, the third quarter of 2026 was an important one for uniQure and for people impacted by Huntington's disease. We believe that AMT-130 has demonstrated a meaningful slowing of disease progression and has the potential to provide treatment benefit for people living with Huntington's disease. We now look forward to working with the regulatory agencies to bring AMT-130 to patients as soon as possible.

With that, operator, please go ahead and open the call for questions.

[Operator Instructions] So our first question comes from the line of Debjit Chattopadhyay with Guggenheim Securities.

I have a couple. First on AMT-130, if it becomes commercially available in the U.S. next year, how are you modeling potential dropouts from the standard of care cohort in the confirmatory study?

And number two, are you evaluating any alternative delivery approaches to potentially expedite the procedure times?

Debjit, it's Matt here. Walid, do you want to take the first question on the confirmatory study?

Sure. I'd love to. Yes. So Debjit, this is going to be a global clinical study. Early on, we're going to be prioritizing recruitment in the U.S. to get us up and running and be meaningfully recruited, but the reach will be global such that during the conduct of the study, we will be -- we will go to places where we will not be having AMT-130 on the market during the conduct of the study, and that will reduce this.

In addition to this, we're doing a number of simulation, and we have adjusted our sample size to match this. So this eventuality as well, as well as sort of analysis plans to deal with dropouts whenever they happen in the SOC. I turn it over to you, Matt.

Yes, Debjit, on the second question, there is actually a significant amount of work that's going on now looking at procedural adaptations. And these would be things that would potentially be implemented post approval. But a number of these things have the potential to meaningfully reduce procedural time and complexity.

Next question comes from the line of Paul Matteis with Stifel.

This is Matthew on for Paul. Congrats on the progress. I guess maybe a question for Kylie. How quickly would you anticipate patients will be able to get therapy, assuming the positive outcome from the PDUFA? And what would be the gating factor there? Would it be access?

And then another quick follow-up. For the confirmatory study, would the eligibility criteria be similar to the Phase I/II, including the stage of the disease and maybe the striata volume requirements?

Thank you very much for the first question. So with regards to what could potentially be gating factors, I think there's 2 elements to this. Access is, of course, one of them as well as ensuring that we have P&T approvals in the individual institutions to ensure that patients can get access to the therapy and that the institutions can get paid for that.

However, what I would say, while these are traditional gating factors, the team is working very hard to ensure that we do as much preparation as possible ahead of a potential launch to ensure that this is streamlined in the best possible way. So there's a lot of work going on in all the institutions to map the P&T processes, understand how often do they meet what are the requirements that are needed to secure approval and ensure that we're working with the institutions to provide as much information in advance so that it's streamlined at the point of launch.

In addition to that, as I mentioned in the prepared remarks, the team is also working with payers on educating across both the unmet need in Huntington's disease as well as the AMT-130 data package to ensure that we're able to move as quick as possible post launch.

So regarding the eligibility for the confirmatory study, that will be similar to the -- what we did report the Phase I/II, including the striatal volume as well.

Next question comes from the line of Joe Schwartz with Leerink Partners.

Congrats on all the progress. Given the FDA expects the confirmatory study to be well underway and potentially fully enrolled at the time of accelerated approval, and screening starts by year-end and the decision date is about 4 months later on May 1. We were wondering how many patients do you expect to have randomized or dosed by then?

And then for the advisory committee, how do you keep the discussion on the 36-month analysis, which the FDA agreed supports the BLA rather than rearguing the 48-month primary analysis? And then any sense yet of timing or which committee?

Joe, thanks for the questions. Walid, do you want to take them one by one?

Sure, happy to. So the FDA's fundamental intent for the confirmatory studies based on their January 25 guidance is that to make sure that they can be completed in a timely manner after approval. And we are confident we can demonstrate that. We've been starting -- we started to prepare for the study before we engaged fully with the FDA. And after we aligned with them, we accelerated that.

Our goal is to run the study globally, as I indicated, across the U.S., Canada, North America, Latin America and Europe. And we intend also to run it in places where there will not be access during the trial so that there will be lower risk of dropout, which is when the agency is, to a great extent, worried about it if we cannot complete the study.

So with all of these elements in place and making sure that we demonstrate to the agency the full engagement and all the sites across the world that we've engaged with and the momentum for enrollment, we believe that we can present a credible path that would satisfy the agency.

Regarding the AdCom and 48 versus 36-month, it's premature for us to position this. We will be ready to discuss any action. But to a great extent, that will be depending on the agency's briefing book. As you know, in preparation for the AdCom, we are -- we will be preparing for any possible scenario. And we will have to gauge this based on what our specific questions are going to be raising for the AdCom and the briefing book supporting that. So we will get a chance to adjust in due course.

And regarding the committee, I do not have any more information on this, definitely not from the FDA, but I would imagine it will be the typical committee that reviews cell and gene therapy and advanced therapies.

Next question comes from the line of Luca Issi with RBC Capital Markets.

Congrats on the progress. Maybe, Walid can you confirm that you have yet to receive the day 74 letter? And then maybe bigger picture, can you just maybe educate us on what is usually included in that letter? Do you think the FDA will share some of their preliminary concerns in the context of the letter? I guess what I'm trying to ask here is whether there could be anything material in the letter that you need to disclose to the Street as well or not?

And then maybe super quickly, SG&A obviously went up a little bit versus last year, you obviously preparing for the launch. How should we think about the line item going forward maybe before and after the PDUFA?

Yes. Thanks, Luca. Look, as we have indicated that since now, we are in active review process, we will not be providing any updates based on request for information or any other communication with the FDA. Of course, we will respond to them in due course. But unless things are material, we will not be communicating externally.

In terms of usually comes at day 74, that would be one example. If the agency has -- they list their areas of concern and areas that they're focused on, that's usually part of that day 74.

Christian, do you want to answer the SG&A question?

Sure, happy to. Look, as you know, we don't give specific guidance. It shouldn't be surprised that SG&A spend will go up, but we'll maintain our disciplined approach. And it's all built into the runway guidance that we are capable of funding all our products into 2030.

Next question comes from the line of Joon Lee with UBS.

Upon approval in May, how many patients would you be ready to dose in the U.S. and U.K. depending on the approval in U.K., obviously? And what is your manufacturing capacity?

And last question, in the unlikely scenario where the FDA does not end up approving AMT-130, are you still obligated to complete the confirmatory trial?

Kylie, do you want to answer the first question on launch?

Yes, absolutely. I think across the board from a patient perspective, it's a bit premature to provide specific patient estimates. I think what the team is working on extensively is ensuring that we're able to understand what the capacity is at each of the different centers, both in the U.S. and in the U.K. to understand what we think is a reasonable number of centers that need to be operationalized at launch to be able to try and meet the demand as quickly as possible.

So the team is working on that at the moment, and we're targeting a number of institutions that have both HDSA Centers of Excellence as well as ClearPoint in the same institution to ensure that patients are able to be evaluated, move to surgery and then back to neurology very seamlessly. And that is the work that's been ongoing. So while we are not quite there yet to give specific patient estimates, I think a reasonable analog is other gene therapies that have launched recently.

Yes. And maybe I'll answer the next 2 questions. Yes, on manufacturing capacity, we do not expect that to be a constraint. Remember, these are relatively small volumes that we're administering in a targeted and precise way per infusion, this is approximately 500 microliters. So the yields that we get in terms of number of patients that can be treated per batch is meaningfully higher than an IV administered medicine.

On the third question regarding the confirmatory study, obviously, if we're not approved at the PDUFA date, we have to understand the reasons why and what our next steps are going to be. If you're asking more about the obligations related to the confirmatory study, I mean, I certainly think we have a commitment to this patient community, and there would be an ethical obligation to continue with that study. I don't know if it's a legal obligation, but we're absolutely committed to the HD community and completing that study, whether or not the drug is approved and it's a confirmatory study or if it's a Phase III registrational study.

Next question comes from the line of Peyton Bohnsack with TD Cowen.

This is Peyton on for Joe. I guess, can you talk a little bit about the Phase III protocol or trial design and anything that's included to decrease any variability in the TFC measure or make sure that there is the highest chance to detect the difference between the 2 groups?

Sure. I assume you meant the confirmatory study, but Walid, why don't you answer that one?

Yes. Thanks, Matt. Yes, I assume it was on the confirmatory study. So look, we take very good care to try and train the sites and do regular training to make sure that the measurement is really accurate. We're collaborating with HSG, where they are trying to standardize also the administration of the question for TFC. I mean TFC tends to be a bit less noisy. I mean, because this is not like subjective as much in terms of like to what degree you have an abnormal movement in various parts of your body like TMS, which has been shown to be excessively variable. TFC talks about like really crude measures. Can you work full-time? Can you work part time? Can you take care of yourself? And those tend to be a bit much more consistent, I should say. And so we will be doing -- was there another part of the question that I'm missing?

No. I think he asked about...

[indiscernible] Yes. And I wanted to mention also in powering the study, we also were careful. Of course, we don't want to be skating too close to the edge. We base it on information that we have from our ongoing study and took the necessary precautions to make sure that we will have enough power also considering potential dropout in the standard of care patients in the event that happens.

Next question comes from the line of Salveen Richter with Goldman Sachs.

On the launch here, how many certified neurosurgical centers do you expect to be fully trained and operationally prepared to dose commercial patients at approval? And what is the target throughput capacity here?

And then maybe you could just also speak to how you're thinking about the label and whether it will reflect the broad Phase I/II inclusion criteria or whether it's restricted to specific striatal volume thresholds?

Absolutely. So starting with the first question on number of neurosurgical centers and capacity. I think one of the things that is important to note is neurosurgical capacity differs quite dramatically from center to center. And so again, this has been a lot of the work that the team has been doing to understand how many functional neurosurgeons would be able to perform the procedure, how many operating rooms are in place that could be used and then calculating capacity based on those discussions with the centers.

And so you see sometimes something from 2 a week to one a month, and it varies center to center. So the team has been really thinking through what is the capacity at each institution. And as you look across the institutions, how does that scale up on a national level. We're still working through the number that we think will be available at launch. We're certainly going to be north of 15 centers. Could it be 30? Could it be 25? We're still working through that to understand what that could look like and how quickly we can operationalize these centers.

But we're looking at centers with the highest potential capacity initially and then also adding additional centers from there. With regards to the second part of the question associated with the label, I think it's a bit premature for us to comment on that. We're not at the stage of discussing the label with the FDA. However, the way we've thought about the addressable market is assuming stratal volume requirements. And then obviously, if that's not the case, then we would adjust that accordingly.

Moving on to our next question. It comes from the line of Yanan Zhu with Wells Fargo.

I think we should go to the next question, operator.

Next question comes from the line Ellie Merle with Barclays.

Just a follow-up to the earlier question on the number of patients that you anticipate having dosed in the confirmatory trial at the time of like potential approval. I guess, do you have plans to submit additional safety data to the FDA prior to accelerated approval after some of the patients in the confirmatory study have received the initial procedures?

And then just a follow-up question on kind of like additional submissions to the FDA. I guess, if the FDA asked for the 4-year data, would that potentially warrant a major amendment as part of the review and how you're thinking about that as a potential scenario?

Thanks, Ellie. Walid, do you want to answer those?

Sure. Regarding the number of patients, we're -- we are confident that we will be well underway by the time we reach PDUFA. And as I mentioned before, we have a lot of measures in place to be able to complete the study in a timely manner across the world. So pretty comfortable with that.

In terms of the safety data, we will be providing a day 120 safety update, which is typical in this situation. And of course, if there's any patients that have been dosed in the confirmatory trial by that cutoff date, those would be included, should be any patient available by that time.

Regarding the 4-year data, there's been no discussion with the FDA to date regarding the 4-year data in terms of requesting it. But as I mentioned before, if this were to happen during the course of the review, we will not be communicating on this because during the process, unless something is material, we will not be communicating on this. Now as you mentioned, in the event they ask for it, we submit it and they consider that a major amendment and there will be a delay to PDUFA. Of course, that will become material, and we will be sharing that information with you.

Our next question comes from the line of Patrick Trucchio with H.C. Wainwright.

Luis Santos in for Patrick. The question is focused on trying to understand a little bit what could happen in the U.K. and what steps need to happen assuming MHRA approval for fully funded?

And then I would like to also ask a question on your epilepsy data coming up. And I was thinking if you could tell us a little bit more about how do you expect consistency in the patients that were treated with lower dose to inform the expectations for the higher dose?

Thanks for the questions. Do you want to answer the first question, Kylie, on the U.K.?

Absolutely. Thanks, Matt. So with regard to your question around what happens from an access point of view to ensure that AMT-130 can be available for patients in the U.K. What would happen is we would undergo a NICE review. And from there, assuming success, we would begin NHS commissioning, NHS England, NHS Wales and so on and so forth, we would be commissioning with each of the individual countries in the U.K.

So what we have done is begun engaging from an early scientific point of view with both NICE and NHS England to ensure that we're able to understand how they're viewing Huntington's disease, how they're viewing the AMT-130 package. And then ultimately, we'll be in a position next year to be submitting the dossier to ensure that we're starting that process immediately upon approval.

So for the AMT-260 question in MTLE, the really Phase I studies are there to learn. We dosed 6 patients in the low-dose cohort. We had great results in probably half the patients, and the others did not respond as well. We continue to follow them, and we will provide you also an update during the first half of next year on those patients.

In addition, we now fully dosed 7 more patients in the higher dose cohort. And depending on the results, we will be able to interpret the data, one possibility. If we find very consistently positive results, then there would be one interpretation. If that's not the case, then we need to figure out what would be the next step. So those would be part of the evaluation that we will do, and we will be sharing that information with you in the first half of next year.

Another element we do in the Phase I study is to look at safety. And in the first cohort, that profile was fairly good at this stage of development. So we were encouraged by that, and that allowed us to go to the higher dose cohort. And again, we will be sharing with you the results in the first half of the year.

Next question comes from the line of Rudy Li with Wolfe Research.

This is Devin on for Rudy. Just had a question on AMT-260. Can you talk about the differentiation versus Neurona and RTX-1001? And what is the bar for a no-go versus a go decision for the ongoing study?

Walid, do you want to take that?

Sure. Well, again, we're early in development. So our goal right now is to evaluate the risk benefit and -- of this product and see whether there's clear evidence of activity. Our goal in the end would be to be best-in-class, and that will determine -- but that will be determined after an appropriately well-controlled trial that we can do. At this point, we are still in the signal detection mode. And as always, we are very careful in making a go/no-go decision. So we're still gathering that information. We will share with you an update early next year. And based on that, we will tell you which direction based on these data, we will be going next.

Next question comes from the line of Lachlan Hanbury-Brown with William Blair Chicago.

I wanted to follow up on one of the prior questions about the confirmatory trial. You mentioned FDA guidance about having to be sort of well underway at the time of accelerated approval. But I feel like we've kind of seen apply that standard differently across programs. So I was just wondering if you had any sort of explicit discussions with them on how they're thinking about that stand and what well underway means in this instance.

Yes. I think I'll maybe just -- I think it's really the same answer to the question that Walid has mentioned previously. The FDA does have a wide discretion to determine what is meaningfully underway. The spirit of this, which applies to really all accelerated approvals, is that they want to ensure that the execution of confirmatory evidence generation is done in a timely manner.

We -- they obviously are aware that we just are starting the confirmatory study. We've shared with them approximate time lines as part of our communication. The progress that we're making in getting the study up and running is accelerating. We will have an initial focus on enrolling patients in the United States and centers that are already up and running. And we plan to have numerous centers outside the United States assuming the product is approved.

So we're very confident and very committed to the study that we can complete it in a timely manner and then generate the data that is sufficient to support full approval.

Now our final question comes from the line of Sushila Hernandez with VLK.

So for the confirmatory study, could you expand on the primary analysis being assessed at 36 months, what is supporting this time point?

And secondly, how many U.S. centers do you expect could administrate AMT-130 in the first 12 months after approval? How do you look at this development during the initial launch period?

Walid, do you want to take the first one? And then, Kylie, you can take the second?

Sure. Yes. The primary analysis is essentially at 36 months TFC comparing our treated subjects to the standard of care control. Not sure if there's any need to elaborate more. This would be an MMRM analysis, which is typical of these types of studies. Kylie?

Thanks, Walid. And with the second question, across the U.S., there's more than 60 HDSA Centers of Excellence. And then when you layer over the top of that centers that also have ClearPoint capabilities, you get to north of 100. This is obviously not what we're targeting in the first 12 months. And as I said earlier, that number has not been locked down yet. We're working through understanding the capacity at each of the different institutions in the U.S. and then trying to look at demand in the first 12 months and saying, what do we think is needed to be ready to go on day 1? And then ultimately, how do we build that up over the first 6 months, 12 months, 18 months and so on.

So we're going to be having a certain number of capacity at launch, which, as I said, is going to be north of 15 centers, whether it's 25, whether it's 30, that number has not been defined yet, and then we will build from there.

So this concludes the question-and-answer session and our call today. Thank you all for joining. You may now disconnect.

Good morning and thank you for standing by. My name is Jeannie, and I will be your conference operator today. At this time, I would like to welcome everyone to the uniQure Phase I/II AMT-130 Huntington's Disease Program Update. [Operator Instructions] I would now like to turn the conference over to Chiara Russo, Senior Director of Investor Relations.

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., EU and the U.K. This update consists of data on clinical endpoints and 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 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 securities 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 if 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. And 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 2 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 3 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 patients 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 missingness 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 48-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 dependency with the high dose showing a 1 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 3 additional patients, the 36-month data demonstrated 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 subdomains. As a reminder, the 3 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, 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 3 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; and 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-month 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 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 3 years. These correspond to an average decline of 0.5 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 analysis 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, 3 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 2 patients who dropped out at 12 and 15 months. There is an important comparator 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, prespecified the most current ENROLL-HD dataset released in September 2025. We'll refer to this as ENROLL-HD B throughout this presentation. Last year's 36-month analysis used the January 2023 released dataset, which we'll call ENROLL-HD A. ENROLL-HD B contains everything in ENROLL-HD A plus more than 2.5 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 one is significant factor in the choice.

Our primary analysis follows the same plan as the 36-month analysis in 2025 that supported the BLA submission. The primary endpoint compares the change from baseline in cUHDRS at 48 months in the high dose against the propensity score matched control group from ENROLL-HD B. TFC is a key secondary endpoint.

This slide shows the high dose in orange and the low dose in purple across all patients. The panel on the left shows all available data. The panel on the right shows data from the 12 patients at the high dose and the 12 patients at the low dose for whom we have results up to 48 months. Since last year's update, these 24 patients accrued data from month 36 to month 48. There are several key observations worth noting on this slide. First, there is a softening of approximately 0.5 point between month 36 and month 48 on the high dose. Two components of the cUHDRS drive this. SDMT, which declined somewhat after month 36, perhaps a regression to the mean following relative stability between month 34 and 36, and TMS, which was noisy with a few patients showing very large swings between month 36 and month 42.

Second, we see dose dependence across 4 years, suggesting a treatment effect. This observation matters because it does not rely on a matched external control. The high dose, which is 10x higher than the low dose, shows evidence suggestive of disease slowing when compared to the low dose. Third is, after 4 years, the low dose, which can be considered [ an active ] placebo, meaning it's expected to produce a lower therapeutic effect and could serve as an internal reference, shows a decline of approximately 2 points on cUHDRS. That is in line with the 0.5 point decline per year in the matched external control in the 2- and 3-year analysis reported over the last 2 years. Lastly, the results at 48 months are still missing the 3 patients who have not yet reached the 48-month mark in the study and at month 36 showed a slower rate of decline than the 12 patients who reached that time point a year earlier.

As noted, our primary analysis uses ENROLL-HD B. On the left panel, that analysis shows a 44% slowing of disease progression on cUHDRS with AMT-130 high dose compared to the matched controls, not statistically significant at p=0.144. It is noteworthy that the decline of the matched controls at month 48 is 1.61 points, which is only slightly more than the 1.52 points at month 36 that we reported last year using the matched control from ENROLL-HD A. I will address this topic later in my presentation.

On the right panel, we show the results with TFC. TFC is a key functional endpoint. It is the most direct measure available of what patients and families care about. It captures whether someone can hold a job, manage their own finances and live independently. TFC is also favored by regulators and the primary endpoint for our confirmatory study. In this primary analysis, TFC shows 61% slowing compared to the matched external control with a nominal p-value of 0.008. Similar to cUHDRS, the decline in the matched controls from ENROLL-HD B is lower at 0.94 points at 48 months on TFC compared to 0.88 points at 36 months in last year's analysis using ENROLL-HD A. These graphs show the time course for both endpoints.

Again, I'll point out that the 48-month data do not reflect the complete high-dose dataset as the 3 additional patients included in the 36-month data has not yet reached this time point. Both cUHDRS and TFC show continued treatment effect through 48 months. These are the results for the other cUHDRS components, who all show favorable trends relative to external controls. The Stroop test remains strongly positive with significant nominal p-values. As mentioned previously, SDMT shows some softening between month 36 and 48 and Total Motor Score is relatively noisy.

Let us take a closer look at the ENROLL-HD B matched controls. Participants with longer follow-up tend to decline more slowly, which enriches natural history comparators with slower progressors over time, a known phenomenon in natural history studies in many different rare diseases. The graph on the left clearly illustrates this point in the cohort of participants matched the AMT-130 high dose. Participants whose last data point was at year 1 declined 0.91 points per year on cUHDRS. Those who remained through year 4 or beyond declined by 0.41 points per year, less than half the rate. And the effect compounds over time with each additional year of follow-up selecting for slower progressors.

Missingness in ENROLL-HD B was also greater than ENROLL-HD A, exceeding 50% at year 4, which we believe further accentuates the survivor bias in this dataset. The graph on the right shows the consequence. ENROLL-HD B declined 20% less than ENROLL-HD A at 48 months. Notably, ENROLL-HD B begins flattening after year 2, inconsistent with known disease biology, while ENROLL-HD A continues a linear decline consistent with expectations for early manifest patients. We believe these factors understate disease progression in external control and therefore, the treatment effect of AMT-130 and that this bias compounds with longer follow-up.

Given our observations on ENROLL-HD B's underestimation of disease progression, we conducted a post-hoc analysis using ENROLL-HD A, the dataset used in our regulatory submissions to the FDA and MHRA. On the left, this graph shows 54% slowing at 48 months in cUHDRS, nominally significant with a p-value of 0.041. I draw your attention to the fact that in this analysis, the level of missingness is lower than ENROLL-HD B as more than half the patients matched at baseline remained in the study at 48 months.

In addition, the decline in cUHDRS at month 48 in the control group is 1.94 points, which is closer to the 0.5 point per year we have reported in the prior analysis. On the right, we show the results for TFC with a 68% slowing and a nominal p-value of less than 0.001. The data appears to be robust. Patients who received AMT-130 high dose showed very little decline 4 years after dosing on this measure of real-world functional abilities. For many of these patients, that means preserving a greater degree of independence, the ability to work and to care for oneself, which is highly clinically meaningful. This slide shows the time course over the 48 months compared to the matched controls from the ENROLL-HD A and the dashed gray line from the post-hoc analysis. The solid gray line shows the matched controls from the primary analysis for reference.

Let's turn to the results at 36 months, the time point used for our primary BLA submission and pre-agreed with the FDA for the confirmatory trial. These are the data we shared last year, the original 12 high-dose patients through 36 months shown in the orange dotted line. Adding the 3 additional patients who have since reached 36 months shown in the solid orange line, we see they're progressing more slowly than the original 12, favorably affecting the mean change from baseline for both cUHDRS and TFC. The gray line is the matched natural history control from ENROLL-HD B as prespecified in the primary analysis.

These are the results at month 36 from the primary analysis. AMT-130 high dose showed a robust 80% reduction in cUHDRS decline and a 67% reduction in TFC decline with nominal p-values of 0.005 and 0.011, respectively.

Now that the analysis includes every patient who received the high dose in the study, we believe these data further strengthen the September 2025 analysis that form the basis of our regulatory submission. Across the other components of the cUHDRS, AMT-130 high dose showed favorable results ranging from 59% slowing on Total Motor Score to over 120% slowing on the 2 cognitive endpoints, SDMT and Stroop, both with nominally significant p-values.

Turning to neurofilament light chain or NfL. From month 18 onwards, both doses trend near baseline. At the 48-month cutoff, mean change from baseline in CSF NfL was 4% above baseline on high dose and 8% below baseline on low dose. For context, healthy subjects aged 40 to 60, matching our population, typically show a 1% to 3% annual NfL increase, while untreated early manifest HD patients show a 10% to 15% annual increase. Therefore, we believe the baseline NfL levels after 4 years are well below what would be expected absent effective treatment.

Let's look at safety next. AMT-130 was generally well tolerated. The most common adverse events relate to the administration procedure, all of which resolved. Since September 2025, there have been no new treatment-related serious adverse events in Cohort 1 and 2 at either the low or high dose. As previously disclosed, since our September 2025 update, there was one treatment-related serious adverse event in Cohort 4, the low striatal volume cohort. CNS inflammation in high-dose patient fully resolved with a short course of corticosteroids. There was also a suicide in a low-dose patient, approximately 5 years post treatment assessed as unrelated to therapy.

Unfortunately, people with Huntington's disease experience a 9x higher risk of suicide relative to the general population, making it one of the disease's leading causes of death. This table provides the full adverse event data supporting the summary on the prior slide. In summary, AMT-130 continues to demonstrate meaningful slowing of disease progression. With all patients having reached 36 months, we again see a substantial treatment effect, reaffirming the basis of our BLA submission. The 48-month analysis shows continued evidence of meaningful slowing of disease progression as measured by both TFC and cUHDRS. The dose dependence observed between the low and high dose across 48 months supports evidence of biological activity. We believe survivor bias and missingness in the updated external control likely understate both disease progression in this population and the treatment effects observed with AMT-130 at 4 years.

Overall, AMT-130 continues to be generally well tolerated. To conclude, we believe that there is clear evidence that AMT-130 has the potential to slow disease progression and provide people living with Huntington's disease, the opportunity to maintain a higher quality of life for longer, which is incredibly meaningful to this community who have no approved disease-modifying treatment options. Before I turn over this presentation to Dr. Sung, I want to say that these data will be presented at a future scientific meeting. We continue to make progress towards bringing this potential therapy to patients. We have submitted the BLA to the FDA and expect acceptance in the fourth quarter. We also submitted the MAA to the MHRA, which has since validated the submission.

We are committed to a timely execution of the confirmatory study. Preparations are on target. We expect the first patient to be screened before year-end. We're also busy advancing commercial preparations and look forward to providing more color on launch strategy early next year.

With that, let me turn over to Dr. Sung, who will provide his take on these results. Victor?

Thank you, Walid, and good morning, everyone. I'm Dr. Victor Sung, Director of the Huntington's Disease Clinic at the University of Alabama at Birmingham, and I'm pleased to be here today to provide a clinical perspective on this additional data for AMT-130. My comments are based on my own clinical expertise and experience with AMT-130 as a site investigator on this study.

Since the HD gene was first sequenced over 30 years ago, we have been on a quest to find a therapy that can slow the progression of the disease. But today, there is still nothing. There are currently no FDA-approved therapies to slow the progression of Huntington's disease. The biology is one of inevitable progressive decline. With that backdrop, the data from the AMT-130 program remain encouraging to me. On their own, they provide stronger evidence of a clinically meaningful effect over 4 years, a trend that continues to point in the same direction on both cUHDRS and TFC, 4 years after a single administration is a pattern that I want to keep watching closely.

But my impression is that the totality of the data point toward a meaningful treatment. I think it would be helpful to underscore at least 2 factors in my evaluation of the data. First, I think it is worth revisiting and emphasizing that the 3-year point remains the time point that is the grounding for the BLA and confirmatory study for a reason. Three years is long enough to see a measurable difference in disease progression, but short enough to align with an individual patient's research participation window. I certainly welcome uniQure's production of longer-term data to provide additional context, but it is not necessarily the case that longer-term data are more indicative of benefit than 3-year data.

Second, as a clinician working with patients with this disease, I think of the data in terms of its real-world significance. When I look at an external control that appears to decline more slowly in patients with longer follow-up, that would be contrary to my impression and knowledge of how the disease typically progresses. It is also contrary to how I see my patients progress in their disease. This speaks to why TFC matters clinically, and in my assessment of the data at 36 and 48 months, it isn't just another statistical score. It tracks whether a patient can still hold employment, manage finances, perform chores and care for themselves.

In the real world, as opposed to statistics, patients can either do these things or they cannot. The sustained treatment difference on that measure through 4 years suggests to me that the treatment effect may be translating into real functional capacity for these patients despite a less than conclusive primary analysis. I am also encouraged that the confirmatory study will be grounded in a measure that relies on real-world function as an assessment.

A deeper look at the data and an eventual full panel at 48 months may help understand the longitudinal clinical profile a bit better. But it is relatively clear to me that if the performance presented today were reproduced in the wider patient population that would still constitute a meaningful improvement for patients and their families. We will slow this disease before we stop it. And on balance, I believe this data represents a meaningful step toward doing exactly that. And I'm happy to reflect on it with you today.

And now I'll pass it back to CEO, Matt Kapusta, to lead the Q&A.

Thank you very much, Dr. Sung. With that, operator, we're ready to open the call to Q&A. Thanks.

[Operator Instructions] And your first question comes from the line of Moritz Reiterer with Guggenheim Securities.

This is Moritz on for Debjit. So assuming AMT-130 does receive accelerated approval, perhaps for both the uniQure team and for Dr. Sung, what do you think will be the impact of this 4-year data on AMT-130's ability to gain market share? And maybe just one quick follow-up. Could you just clarify which data at this point has actually been submitted to the FDA and MHRA? Is it just the n equal 12 patients? And is it compared to ENROLL-HD A or B?

Yes, Moritz, it's Matt Kapusta. Thanks for the question. Let me take the second question first. So the data that's been provided in the BLA submission is the data that we presented last year. That was the data that was agreed to with the FDA that could be the primary basis of the BLA submission, and that data incorporates 12 patients at the high dose, and it's compared against ENROLL-HD A, which was the ENROLL-HD data cut that we presented last year.

For the second question, I'll pass it over to Kylie.

Thank you very much for the question. I think one of the things that's important is we remain highly confident in the ability of AMT-130 to meaningfully slow disease progression, which is of profound importance to HD patients who currently have no disease-modifying treatments. As Dr. Sung said today, we think the 3-year time point is incredibly important because it balances the ability to show meaningful slowing of disease and also balances the natural history components as well as the elements of research participation for patients. So we think this is -- this 4-year data is additional longer data that helps demonstrate that meaningful slowing of disease.

Yes. And I just -- I want to add one thing. I mean, when you step back and you look at 4 years after a single administration, these patients haven't even lost the full point in cUHDRS. They haven't even lost 0.4 point in Total Functional Capacity. This is clinically meaningful for patients. And I think with the additional follow-up data, we believe that this is -- there's a significant unmet need here that needs to be filled. Dr. Sung, do you want to add any comments?

Yes. I mean my main comment like you were alluding to, Matt, is just that in a setting where we have no approved therapies that can slow the progression of the disease, the 48-month data still offers that we are still slowing the clinical progression of the disease. And from the perspective of my patients that are -- that have been treated and are in the study, they're still holding very stable. So I think that's kind of the lens that I look at it all is we don't have anything else that can slow the progression, and this is still doing that at 4 years, which is still significant.

Your next question comes from the line of Joe Schwartz with Leerink Partners.

It's pretty striking how TFC holds up better than cUHDRS even against the updated control dataset, which is plagued by survival bias. Why do you think that is? And then what led to using the updated ENROLL-HD cut? Was this an FDA request or your own choice? Do you think the FDA will rerun the 36-month analysis and with the updated data set? And do you think that, that could constitute a major amendment?

All right. So this is Walid. I'll take the questions. There was a bunch of them. So look, TFC is the endpoint that matters most to patients, to clinicians and also to regulators. It measures function and any decline there actually has immediate consequences to people's quality of life, whether they're able to hold a full-time job or take care of themselves. And that's why it tends to be much more relevant. It's very impressive that after 4 years, as Matt indicated, we -- the 12 patients that reached that time point only lose 0.3 points.

CUHDRS tends to be a little bit more sensitive. It picks up on some of the cognitive endpoints and the Motor scores. We've had some noise in the Motor Score and the cognitive tests sometimes show variability and performance could change based on what's happening on that given day, whereas TFC is better -- it gives you a much better sense of what's going on overall with the patient. So I think it reflects more how they're doing in general. And I think that's what we are seeing here.

In terms of why did we use the new cut of ENROLL-HD. Well, ENROLL-HD is an ongoing study. CHDI releases data updates as over time, every few years. And they released a data update in September 2025, which was between the last time we did the analysis on the 3 years. At that time, we used the most updated ENROLL-HD data cut. And now when it was time for us to evaluate the 4-year data, we did what was the right thing, which is to use the most recent ENROLL-HD data cut that provides 2.5 more years of follow-up on the existing patients and 6,000 more participants has more contemporaneity compared to our study, and that's really what regulators usually look for.

It's difficult for me to speculate what will the FDA do, whether they will rerun the analysis with the new data cut or not. That is something that we will deal with if the FDA asked us to run it or if they run it themselves.

Yes. I mean I will add that we have rerun the 36-month analysis with ENROLL-HD B, and the results continue to be very meaningful. The divergence between ENROLL-HD A and B really become more striking at 48 months. They're starting to diverge at 36 months, but it's more modest. And so the impact on that analysis, even if it is rerun is not incredibly meaningful.

I noticed there was also a question about major amendments. If we add the data, it's really very difficult for us to speculate. If the FDA asks for the data, we definitely will provide it. And it's at their discretion whether they believe this is a major amendment or not.

Your next question comes from the line of Paul Matteis with Stifel.

In the past, you commented that ENROLL-HD patients at some of the earlier time points like 2 and 3 years performed fairly similarly on these endpoints as compared to some of the other Huntington's disease natural history studies. Is that still the case with ENROLL-HD B? And is that still kind of the case at 4 years? Sort of, I guess, taking a step back, I mean, I guess the reason why I ask is I think many of us are trying to think about what are some of the sensitivity analyses FDA might do.

So one logical one would be to kind of look at other natural history cohorts that are out there and available. So maybe that's one piece. And then really just on that other side of that, like what other sensitivity analyses here do you think might be relevant stress test of the data that the agency could do? And how many of these have you done yourself?

Well, thanks, Paul. First, on ENROLL-HD, and I think I mentioned this a little bit in my presentation. We have started sharing external -- comparison to external control starting with the 2-year time point, if you recall, at that point, we compared to TRACK and PREDICT. And at that point, again, it was equivalent to the matched controls are declining by 0.5 point on cUHDRS and 0.3 points on TFC.

Last year, when we updated on the 3-year analysis, just because over time, there's not enough patients in TRACK and PREDICT to be able to be matched at the 3 years, they suffered from significant level of missingness. We switched to ENROLL-HD A, which is more robust. And again, it showed that at 3 years and actually throughout the year 1, 2 and 3, 0.5 point on cUHDRS and 1/3 of a point on TFC. This is the first time that we see with ENROLL-HD B. And as we showed in the presentation, there's a break between starting to see at year 2, very evident by year 4, where you see a significant break from this linear progression in the end, averaging about 0.4 points on cUHDRS, which is 20% lower.

So we do think that the data overall support the previous analysis. And the other piece that I want to say is that if you look at our internal control itself on the low dose, even if you assume that there's no efficacy whatsoever on that dose, they also declined about 0.5 point on cUHDRS.

So I do think that the overall analysis do support the fact that beyond 3 years, ENROLL B is really suffering from this survivor bias and underestimating the decline in the natural history cohorts.

In terms of sensitivity, we've run a number of sensitivity analysis, more than 10 approximately, which were prespecified and included in the SAP. And across all of those -- across the majority of those, I should say, we have better percent slowing of disease progression, a higher level of decline in the control, getting closer to that 2.0 that we talked about, and we reached statistical significance and more than half of those. In fact, the primary analysis that we shared with you was the more conservative of the group. So I think that, kind of, answers your question.

Your next question comes from the line of Joseph Thome with TD Cowen.

Maybe just the first one, can you talk a little bit about the consistency of response in the high-dose patients? I think Dr. Sung mentioned that overall, his patients seem to be relatively stable. So is the decline between year 3 and year 4 driven by a few patients or any context around that? And then maybe for Dr. Sung, if you could just talk a little bit about if this is approved, maybe what proportion of your patients you think would be good candidates for therapy kind of like within the first year or so of launch?

Thanks, Joe. Yes, the data overall are very consistent. There's little changes from an outlier. Maybe one exception on cUHDRS, which is driven by that TMS that I mentioned. There was some noise in the data, and there was one particular individual that probably was pulling the average down significantly compared to last year. We're following this with the site. But overall, if you look across the remaining patients, they're all showing consistent results and particularly on TFC, they're all continuing to progress or not progress actually at the case it is between year 3 and year 4. And I'll turn it over to Dr. Sung for the second question.

Yes. I think for the first thing, I feel like the TFC is more representative of what I'm seeing in my patients. I really didn't see any drop-off between year 3 and year 4, minor is still holding steady. So I think as Walid said, some of this may be statistical noise by one patient, and I think TFC kind of is more truly representative there of that stability.

As far as if this were to be approved, what percentage of my overall patients do I think would be good candidates? I mean, I think in the -- I mean, it's complicated because who would be -- who I think medically would be good candidates combined with who would necessarily want a brain surgery for it and who would be able to afford it and those kinds of things. But I mean, I think it's going to be in that obviously, this is really better in the early mild stage, so in the kind of 20%, 30% range of my patients, I would consider strongly as a candidate for it, but I think that's still a pretty sizable population overall.

Your next question comes from the line of Ellie Merle with Barclays.

I guess just given the lower interpretability of the external control data from year 4, how should we think about the meaningfulness of even longer follow-up data at 5 years and beyond? And has the FDA given a stance on how they view the quality of external control data at these longer time points? And also, I guess, is there any way to mitigate statistically the survivor bias in the external control?

Thanks, Ellie. Yes, you bring a very good point. I mean, I think there is an optimal point beyond which natural history becomes very difficult to rely on because, again, they lose a lot of patients and you have significant missingness and survivor bias that really underestimates the treatment effect. So we are working with experts to see how best to analyze the data beyond year 3 because in order for us to be able to interpret the results, we need to have a robust methodology.

Now statistically, there are ways by which one can do this. However, those are never really foolproof. And you always -- they can attenuate some of that a little bit, but not to the full extent. So we're going to be working with experts in the field to really use what is accepted as a state-of-the-art way of interpreting these kinds of things, and we will look forward to sharing that with you.

In terms of the regulators, they did not say anything specific about this topic nor was there a reason for them to do so. So I cannot add anything to that point. Maybe I can remind you that the primary analysis is the 3-year, that's the basis of it. And as was mentioned before, we believe that is sort of the sweet spot, so to speak, between having enough decline in the natural history that we can compare to and show that the drug actually is slowing disease progression that this is a length that we can -- that the patient can participate in trials and still find it acceptable to be part of trials.

And this is the optimal length potentially for a natural history like ENROLL-HD beyond which it becomes a bit more difficult. That's why in our confirmatory study, the 3-year time point is the primary analysis. And in that study, of course, we're comparing to a randomized open-label internal control standard of care.

Your next question comes from Luca Issi with RBC Capital Markets.

This is Shelby on for Luca. Maybe for Matt, we've obviously seen that Karim Mikhail will be speaking on Monday as part of the Cell & Gene Therapy Conference by the Alliance for Regenerative Medicine. And we're all eager to hear what he will say more broadly. But what's your take on how he will approach your application specifically? Do you think he'll rely simply on his staff? Or do you think he'll have more of an active role in the ultimate decision similar to what we saw in the past with Peter Marks for DMD? Overall, just curious if you've met with the guy and your thoughts on his regulatory approach. Any color there, much appreciated.

Shelby, Matt here. Thanks for the question. Honestly, I think those are questions that are probably better suited for Dr. Mikhail directly. It's not appropriate for me to answer questions about how we'll interact with the team or behave on our review.

What I will tell you is what I've said now for 1.5 years since some of the organizational changes at the FDA that we are focused on our data. We strongly believe in our data, and we strongly believe that what we've demonstrated at 4 years, quite frankly, is unprecedented, and that this data demonstrates that we can significantly slow disease progression. And it really doesn't matter who's leading CBER, who's the commissioner of the FDA, who's on the review team. What we're relying on is the strength of the data and the incredible unmet need here that exists with HD patients and their families and the lack of options that they have.

Your next question comes from the line of Salveen Richter with Goldman Sachs.

Can you just remind us why there was data missing in the original ENROLL-HD dataset? And why it's believed to be higher in the updated data set? And as you think of rerunning your prior analyses here, how do we think about the 36-month data cut still being stat sig using the new ENROLL-HD?

Thanks, Salveen. Look, data missingness is a well-known phenomenon in any longitudinal natural history. This tends to be biasing against us in this case, of course, because it underestimates the degree to which these controls are progressing. When we looked at the ENROLL-HD previous data cut where we're calling ENROLL-HD A, which was released in January 2023, and we examined the effect of missingness over time, those effects were modest and not as important as what we've seen now with ENROLL-HD B. And as a result, we did not -- we were not concerned about doing the 4-year analysis using an updated dataset from that same study.

Now seeing it the way it is right now, of course, it's an issue, and we need to go back and evaluate what is the best way to analyze the data going forward. Despite that, as you saw and thanks to the results from all the participants, all 17, right? So 15 reached year 3, but the analysis includes also the 2 that dropped out early. All of these data at month 3 with ENROLL-HD B continue to show 80% slowing on cUHDRS and more than 60% slowing on TFC. I think those are driven mostly by the fact that these patients at that time point, our patients who received AMT-130 high dose show remarkable stability. So whether you analyze them with this new data cut of ENROLL-HD, which underestimates the progression at 3 years or the previous data cut, you're having a very robust effect.

Now the question is what do we do going forward, and that's a separate question. But I'm very heartened to see those results. And I do think that they indicate that treatment with AMT-130 is effective at slowing disease progression. The exact percent, there's always error bar around these estimates. But at the end of the day, these people are gaining significantly longer periods of stability, and that's going to translate to meaningful clinical benefit for these patients.

Your next question comes from the line of Yanan Zhu with Wells Fargo Securities.

I was wondering, again, on the ENROLL-HD A and B cuts. Is the missing data at outer years, is that a result of more severe patients dropping out of the study? Or is it the result that more patients simply haven't reached a longer time point and therefore, at longer time point, you will naturally have more missing data? Related to that, I was wondering whether Dr. Sung can comment could the shift between the A cut and the B cut be due to changing standard of care and reflecting that?

And lastly, if I may, TFC is the confirmatory endpoint or proposed confirmatory endpoint. Is there any way that it can be given more consideration for the primary endpoint?

Okay. Thanks for the question. So to answer your question, whether with the new database cut for MHRA, whether the participants would not have had enough time to reach 4 years, that is not possible because we select the patients to have the opportunity to finish 4 years. We call it an effective enrollment period because otherwise, we end up with the situation that you mentioned, and we end up inflating this missingness.

Now these missingness here, well, we don't know exactly why, and we're working with CHDI actually to better understand why is there a difference between the missingness with the previous ENROLL-HD data cut and the new more recent data cut. But what we do know for sure is that those for whom we have data up to 1 year, are progressing much faster than those for whom remain in the trial at 4 years and beyond. And it's the difference is about twofold between these 2 time points. So clearly, those who are having a more severe progression, they are dropping off early, and therefore, they're biasing this.

I'll jump to the TFC bit, and then I'll give the floor to Dr. Sung. The primary analysis that we agreed to support the BLA submission was cUHDRS. But that is an intermediate clinical endpoint that is reasonably likely to predict the meaningful clinical endpoint, which in the eyes of the FDA is TFC.

Now in rare diseases, when you are evaluating the datasets that you have, in general, regulators evaluate the data from all various endpoints that you have in a trial and their prerogative to use the data from TFC even if it's not prespecified as the primary and it's secondary. Even with that, I'll remind you that TFC was specified as a key secondary. And in our hierarchical testing for the 3-year analysis, it was statistically significant following cUHDRS, both in ENROLL-HD A, which was the analysis we submitted to the FDA and in this updated analysis at 3 years.

So from that perspective, I don't think regulators will be constrained to a great extent by what we chose. But regardless, both of them are stat sig. And with that, I'll turn it over to Dr. Sung.

Yes. I wanted to briefly address, I think the tone of your question really is there something with ENROLL-HD where this data is not there between year 3 and year 4. ENROLL-HD has been going on for over 10 years. We've been at site for over 10 years. So there's lots of data in there. But, as Walid has said, there's just this thing with all natural history databases that patients drop out more over time. And as far as why there's a difference between ENROLL-HD A and B as far as missingness in particular, there's things that we speculate about. And as Walid said, we're going to discuss that with CHDI further to get some color there.

I have my own thoughts on that, but I think it's all speculative at this point. And then to address your question, has there been a change in clinical standard of care that could account for the difference between ENROLL-HD A and B? I would say no. I don't think there's any new medications that have come out or treatments that would cause especially in a mild group like this all of a sudden for them to deflect and stabilize between year 3 and year 4. I don't think it's that. I think it really is the missingness of the data as we've discussed.

Your next question comes from the line of Patrick Trucchio with H.C. Wainwright.

This is Cynthia for Patrick. For the same 2 high-dose patients and the same matched control methodology, what is the month 36 to 48 cUHDRS treatment effect bridge? Or what do the individual high doses -- high-dose cUHDRS trajectory show between months 36 and 48?

Cynthia, can you clarify, you mean the 12 subjects who completed the 48 months? How did they look at 36 months versus 48 months? Is that what you're asking?

Yes. basically, for the same 12 high-dose patients using the same matched control methodology, could you maybe walk us through the -- how the cUHDRS treatment effect changed from 36 to month 48, including changes in the treated and control groups?

We have not conducted a statistical analysis model only on the 12 completers. The matching is done on all of our AMT-130 treated subjects. So all I can tell you is that the observed difference from baseline, which we show on our slide, at year 3 for the 12 patients on cUHDRS was 0.38 and at year 4 is 0.9. And that is the difference that we see in those 12 patients. I'm not sure if I'm answering your question correctly, but that's as best I understood it.

[Operator Instructions] And your next question comes from the line of Lachlan Hanbury-Brown with William Blair.

So maybe just, sort of, following up to a degree on that last question on the sort of discordance in progression between cUHDRS and TFC from month 36 to month 48. Walid, I think you were saying earlier that's driven mainly by sort of noise from maybe 1 or 2 patients on other parts of the cUHDRS. Can you maybe just, a, confirm that I heard that correctly, but b, what for those patients, like what does that actually look like clinically? I mean you've highlighted that TFC is sort of what matters. So what does it look like for a patient that's pretty stable on TFC, but declining more on cUHDRS in the real world?

Yes. So let me be very clear. The -- for cUHDRS, we see -- we think that the decline or what we see in the subcomponent mainly driven by 2 of the scales, SDMT, where a number of patients have shown a decline between year 3 and year 4. This is a cognitive test. And TMS, which tended to be noisy with a couple of patients showing really significant change versus their previous one -- previous measure, which is not really consistent with also how they were doing on TFC as well.

What I can tell you is that I believe that, again, TFC measures almost how a patient has been doing and is doing with a little bit of more going back over time, a few weeks or a few months, whereas when you do the cUHDRS, which is an evaluation of cognition, cognitive test and TMS, those are sort of time bound. So what -- however you were feeling that day or they sometimes could depend on the effort that you put in and so on and so forth.

So cUHDRS has to be more sensitive to pick up certain things, but it's also more variable because it doesn't have that what I like to call area under the curve, like how have you been doing in the past few weeks? Because if you're not able -- if you've lost your job or you're not able to function because you're losing performance, then that will be reflected in TFC. If one day, you're a bit off in the way you're performing on a cognitive test, that will be reflected directly on cUHDRS. So that's how I can best respond to this question.

Ladies and gentlemen, this concludes today's conference call. Thank you all for joining. You may now disconnect.

Hello, and thank you for standing by. My name is Joy, and I will be your conference operator today. At this time, I would like to welcome everyone to the uniQure Second Quarter 2026 Earnings Call. [Operator Instructions]

I would now like to turn the call over to Chiara Russo, Senior Director of Investor Relations. Please go ahead, ma'am.

Good morning, and thank you for joining us for uniQure's second quarter of 2026 earnings call. Earlier this morning, uniQure released financial results for the second quarter of 2026, and our press release is available on the Investors and Media section of our website at uniqure.com. Our 10-Q was also filed with the SEC earlier today.

Joining me on the call this morning are Matt Kapusta, Chief Executive Officer; Dr. Walid Abi-Saab, Chief Medical Officer; Kylie O'Keefe, Chief Customer and Strategy Officer; and Christian Klemt, our Chief Financial Officer. After our formal remarks, we'll open up the call for Q&A.

Before we begin, please note that we will be making forward-looking statements during this investor call. All statements other than statements of historical facts 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 conference call. 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 most recent SEC 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 if new information becomes available in the future.

Now let me introduce Matt Kapusta, uniQure's CEO.

Thanks, Chiara. Good morning, and thank you for joining us this morning. The second quarter was an important one for uniQure. We received guidance from both the FDA and MHRA, our near-term regulatory pathways for AMT-130, announced promising early data from our Fabry disease and refractory temporal lobe epilepsy programs and strengthened our balance sheet into 2030 through a follow-on offering. Taken together, these developments meaningfully advance our ability to deliver transformative therapies to patients with serious unmet needs.

On today's call, I will provide a brief overview of the quarter before turning to Walid for an update on our clinical programs, Kylie on commercial readiness and Christian on the financials. I will then offer some closing remarks before opening the call to analyst questions.

I want to start with AMT-130 and the progress we have made with our FDA interactions. In June 2026, we held a Type B meeting with the FDA during which we reached alignment with the FDA that a BLA submission under the accelerated approval pathway for AMT-130 based on the 3-year data is reasonable. This alignment was later confirmed in the final meeting minutes we recently received. The FDA asked to align the confirmatory study design prior to the BLA submission, including the consideration of a randomized standard of control design instead of a sham procedure.

Additionally, consistent with the agency's January 2025 draft published guidance for accelerated approvals, the FDA stated that the confirmatory study should be feasible to conduct within a reasonable time frame and be well underway and potentially fully enrolled at the time of accelerated approval. We are fully committed to initiating the confirmatory trial as soon as possible after alignment has been reached.

The FDA recognizes that HD is a serious disease with a high unmet need for safe and effective therapies, and we are working collaboratively with them on a confirmatory study design. We are on track to submit the BLA this quarter, and Walid will provide additional details later in the call. In parallel, after a successful presubmission meeting with the Medicines and Healthcare products Regulatory Agency or MHRA earlier this year, our U.K. regulatory submission is also on track as planned for the third quarter.

Also in the third quarter, we expect to conduct our 4-year AMT-130 data analyses from the Phase I/II studies. We look forward to presenting the 4-year data results in September. Beyond AMT-130, we are encouraged by the progress across our broader pipeline. Early data from our Phase I/IIa study of AMT-260 in refractory mesial temporal lobe epilepsy and Phase I/II study of AMT-191 in Fabry disease continue to support the potential of both programs, and we look forward to sharing further updates in the first half of next year.

As we prepare for potential commercialization of AMT-130, our team has intensified its focus and execution. We are deeply engaged with the Huntington's disease centers of excellence, payers and the patient community, and we are working diligently to put in place the infrastructure to support what we hope will be a timely and successful product launch.

In summary, we are entering the second half of the year with strong momentum, clear regulatory pathways for AMT-130 in the U.S. and U.K., advancing pipeline programs and a customer-focused commercial organization prepared to deliver. We are grateful to the FDA for their continued engagement and collaboration, to the MHRA for their constructive interactions and above all, to the patients, families, investigators and advocates in the Huntington's disease community whose resilience and trust continue to inspire us every day.

With that, I will turn the call over to Walid to provide additional detail on AMT-130 and our broader pipeline. Walid?

Thank you, Matt. Good morning and good afternoon, everyone. I'll start with AMT-130 in Huntington's disease. As Matt noted, the Type B meeting with the FDA was a pivotal moment for this program and the HD community. At this meeting, the FDA communicated that our 3-year Phase I/II data would be acceptable as the primary basis of a BLA for the accelerated approval of AMT-130.

The FDA also requested that we align on the design of the confirmatory trial to support accelerated approval prior to BLA submission. We're working with the FDA to finalize the design of the confirmatory study. However, the critical point is that the FDA agreed that a randomized study using sham control is no longer required. The agency recommended instead that we run a randomized standard of care controlled study with total functional capacity at 36 months as the primary endpoint.

We are committed to conducting the global confirmatory study and will work diligently to ensure that the study is completed with a reasonable time line. We remain on track for a third quarter BLA submission and look forward to potentially bringing this therapy to patients. On the ex U.S. regulatory strategy, as Matt noted earlier, we are on track with our planned regulatory activities with the MHRA. With our near-term regulatory focus on the U.S. and the U.K., we expect to engage more fully with the European Medicines Agency in 2027 and remain committed to bringing AMT-130 to patients across Europe in due course.

Finally, turning to our clinical progress, I'm very pleased to report that the AMT-130 clinical team is on track with data quality and database lock activities based on the June 30 cutoff date for the 4-year data, keeping us on schedule for the expected September update. We currently plan to disclose safety and tolerability data through 4 years of follow-up. The update will also include top line data from 12 high and 12 low-dose patients at 4 years with an additional 3 patients at the high dose for a total of 15 patients now with 3 years of follow-up.

Clinical data will include cUHDRS and its components such as TFC compared to a propensity score-matched natural history control derived from the Enroll-HD database. We continue to believe Enroll-HD provides a robust and contemporaneous comparator, and we are pleased that CHDI has afforded us the opportunity to incorporate the latest iteration of the Enroll-HD database into the 4-year analysis, which has been recently updated with approximately 6,000 additional HD participants for a total of approximately 26,000 participants to draw from. We also plan on providing CSF NfL change from baseline at 4 years.

Moving on to AMT-260 for refractory mesial temporal lobe epilepsy. This quarter brought the first cohort level readout from the Phase I/II study, which we presented at a medical conference in June. As of May 29, 2026, data cutoff, 3 of 6 patients in the first low-dose cohort achieved meaningful reductions in disabling seizures during months 4 through 6, ranging from 79% to 100% below baseline. The remaining 3 patients showed variable outcomes over the same period, ranging from a 33% decrease to a 36% increase from baseline.

Variability and response at this early stage is not unexpected, and we believe longer-term follow-up and the higher dose cohort data will be important to understanding potential dose response and patient selection. On safety, as of the presentation date, there were no serious adverse events related to AMT-260 or the surgical procedure. All adverse events in the low-dose cohort were mild or moderate, most commonly headache in 2 patients and no immunosuppression was required.

We view this tolerability profile, combined with early signals of biological activity as supportive of continued evaluation at the higher dose. Enrollment in the second higher dose cohort is expected to complete imminently. Updated results for both cohorts are expected in the first half of 2027. Lastly, I will cover AMT-191 for Fabry disease. In June of this year, we presented updated preliminary safety and exploratory efficacy data from the Phase I/II study with the March 15, 2026 cutoff date. Patient follow-up ranged from 3 months to more than 18 months.

Consistent with our disclosure in February, dose-dependent elevations of alpha-Gal A activity were observed in all 11 patients across 3 dose levels, plasma lyso-Gb3 levels remained stable post dose across all cohorts regardless of enzyme replacement therapy or ERT status, and all 11 dosed patients remained withdrawn from ERT. On safety, AMT-191 continued to show a manageable safety profile at all dose levels. Per protocol, additional dosing in the mid- and high-dose cohorts remains paused, pending agreement with the FDA on a monitoring and management plan following the Grade 3 liver enzyme elevations reported in 2 patients from the mid-dose cohort. These events were reviewed and confirmed as dose-limiting toxicity by the Independent Data Monitoring Committee. As of the end of May 2026, these LFT elevations have all resolved following the course of immunosuppression.

Now I will turn the call over to Kylie to discuss our ongoing efforts with the HD community and our U.S. and ex U.S. commercial efforts. Kylie?

Thank you, Walid. I want to begin, as always, by acknowledging the Huntington's disease community, the patients, the families and the caregivers who live with this disease every day, the clinicians who care for them and the advocates who have tirelessly pushed for regulatory flexibility and access. Your trust in us is what drives our sense of urgency and our recent accomplishments are a direct reflection of the work we have all done together. The FDA's communication that our 3-year Phase I/II data would be acceptable as the primary basis for a BLA submission represents the regulatory clarity our commercial team has been preparing for.

With the BLA submission planned for the third quarter and an MAA submission to the U.K. MHRA on the same time line, our commercial preparations have taken on renewed focus and urgency across 3 key priorities. First, treatment center readiness. We have maintained deep and ongoing engagement with Huntington's disease centers of excellence across the United States and the United Kingdom, working closely with the multidisciplinary neurosurgical, neurology and care teams that we believe are critical to a successful launch.

The feedback we continue to receive from the community on the AMT-130 data set and its potential to meaningfully slow disease progression has been consistently strong and continues to reinforce our conviction to have a successful launch. Second, community engagement and education. Ensuring continuity across the care journey, understanding genetic testing and referral pathways and scientific education and communications remains a core focus.

We are actively working to ensure that potentially eligible patients and the providers who care for them remain informed as we continue our commercial preparations. Third, market access readiness. Payer engagement is advancing in both the U.S. and the U.K., underpinned by a robust health economics and outcomes research program that continues to build the evidence base for the potential long-term clinical and societal value of AMT-130. Potential approval in either the U.S. or the U.K. would also unlock the potential for named patient and early access programs in additional geographies, including the Middle East, Latin America and Central and Eastern Europe, extending our potential reach to patients ahead of formal reimbursement decisions locally.

Turning to AMT-260 in refractory temporal lobe epilepsy and AMT-191 in Fabry disease. Our teams continue to deepen center of excellence relationships, refine the patient and provider journey and build the evidence base needed to support potential future development decisions in both indications. We remain energized by the early clinical signals from both programs and are laying the strategic groundwork in parallel with clinical development.

I'll close by saying that we believe the opportunity to potentially deliver the first disease-modifying therapy to patients with Huntington's disease is closer than it has ever been. We are energized by the potential of AMT-130. And as we continue to engage with treatment centers, build pathways for patients and interact with payers, our organization will be ready as the HD community has waited long enough.

Now I will turn the call over to Christian for a financial update. Christian?

Thank you, Kylie. I'll be sharing the financial highlights of the second quarter of 2026. Please refer to the earnings press release issued this morning and our quarterly filing with the SEC for additional details.

Revenue for the 3 months ended June 30, 2026, was $5.8 million compared to $5.3 million in the same period in 2025. The increase of $0.5 million is due to the increase in license revenue compared to the prior period. Research and development expenses were $34 million for the 3 months ended June 30, 2026, compared to $35.4 million during the same period in 2025. The $1.4 million decrease was driven by a $3.2 million decrease in other research and development expenses, partially offset by $1.8 million increase in direct research and development expenses.

The decrease in our research and development expenses primarily reflected a $1.5 million decrease in facility expenses, a $1.3 million decrease in employee and contractor-related expenses, including share-based compensation and a $1 million decrease in the fair value of contingent consideration, partially offset by a $0.5 million (sic) [ $0.6 million ] increase in information technology costs.

The increase in direct research and development expenses reflected higher spend on the AMT-260, AMT-162 and AMT-191 programs, partially offset by lower spend on AMT-130 compared to the prior period. Selling, general and administrative expenses were $17.4 million for the 3 months ended June 30, 2026, compared to $13.5 million during the same period of 2025. The $3.9 million increase was primarily related to a $4.3 million increase in employee and contractor-related expenses, including share-based compensation, mainly as a result of a higher number of employees recruited in the second half of 2025 to support the potential commercial launches of AMT-130, a $0.7 million increase in intellectual property fees and $0.7 million increase in information technology costs and other expenses.

This was partially offset by a $1.8 million decrease in professional fees, primarily as a result of lower costs incurred in support of the potential commercial launches of AMT-130 compared to the prior period. Cash, cash equivalents and investment securities totaled $810.3 million as of June 30, 2026, compared to $622.5 million as of December 31, 2025. We believe that uniQure continues to be well positioned to execute on its clinical and operational priorities through 2026. We expect that cash, cash equivalents and investment securities will be sufficient to fund operations into 2030.

I'll now turn the call back over to Matt.

Thank you, Christian. To summarize, we entered the second half of 2026 with clarity on our regulatory pathway for AMT-130, both in the U.S. and U.K. With the submission of multiple license applications for AMT-130 and the anticipated release of 4-year data, the coming months represent potentially transformational milestones for uniQure and for the HD community we are committed to serving. In parallel, we continue to execute across our pipeline with disciplined capital allocation, supported by a strong balance sheet that we expect to fund operations into 2030.

Before we open to questions, I want to note that with the June 30 data cutoff passed, we are in a quiet period on the AMT-130 4-year data and will not be providing further commentary ahead of our September readout. We very much look forward to sharing those results with you then.

Finally, I want to take a minute to sincerely thank my leadership, regulatory and clinical teams. I am truly motivated by their perseverance and unwavering commitment to the patients and families for whom we aim to deliver potentially life-changing therapies.

With that, operator, please open up the call to questions. Thank you.

[Operator Instructions] Your first question comes from the line of Debjit Chattopadhyay with Guggenheim Securities.

Given the strength of the 3-year data, what would you consider to be the best outcome for the 4-year data? And what role do you think the 4-year data are going to play in any potential AdCom that one should expect for a first-in-class therapy for Huntington's?

Debjit, it's Matt. Thanks for the question. As I mentioned on the call, given that we're in a quiet period, we're not able to comment on the 4-year data. Obviously, with respect to an AdCom, that will be at the discretion of the FDA. The package that we're going to be submitting, if there's alignment that, that package is going to be based on the 3-year data.

The package is considered complete and self-contained. Of course, if the FDA requests the 4-year data, we're delighted to provide that to them, whether it's the context of the review or the advisory committee.

Got it. And just one more follow-up here. Given that the confirmatory study needs to be nearly fully enrolled at the time of any accelerated approval, how quickly can the team operationalize this? And any clarity on the number of patients you are likely to enroll in the study would be helpful. And good luck going forward.

Matt, I'm not sure if you guys can hear me.

Yes, we got you.

Do you want me to answer this?

Yes, please go ahead, Walid.

All right. So essentially, it's our belief that the fundamental intent of the FDA is that for all confirmatory studies is to ensure that they are completely or completed in a timely manner after approval, and we are confident we can demonstrate that. We talked about sample size. We haven't yet finalized this with the FDA. So it's kind of premature for us to do this. But suffice it to say that our team has been working on this and expecting a positive outcome from a discussion with the FDA.

We started all of the preparatory activity for a global study that's going to be conducted. So the idea is that most of the recruitment post approval will occur in countries before the drug becomes available in those countries such that we can complete the study on time. We are confident that we will be able to conduct the study and complete it in a timely manner.

And we believe that the way we are taking this approach with the global trial gives us an incredible path to get there. I'm sure there were a couple of other little things that you asked, Debjit. So I don't know if Matt or anybody wants to point me in the right direction or maybe I've answered all the questions so far.

No, I think that was it.

Your next question comes from the line of Joe Schwartz with Leerink Partners.

Congratulations on the impressive ascent here. In speaking with functional neurosurgeons, our takeaway is that AMT-130 delivery is very feasible at expert centers, but commercial uptake might depend less on surgeon willingness and technical ability and more on institutional workflow. As you prepare for launch, what have you learned from trial sites about operational bottlenecks? What are you doing to help address them? And how should investors think about realistic year 1 throughput for activated center?

Thanks, Joe. Kylie, do you want to answer that one?

Yes, absolutely. Thanks, Joe, for the question. I think one of the things that has been incredibly important while we move forward with regulatory discussions has been that the team has not stopped the preparation and discussions with treatment centers of excellence. And this has been incredibly important, as you said, to get them to understand these institutional [ nuances ] that occur across the different hospitals.

And one of the things that we have learned is that no hospital is the same. And so what we have been doing is mapping each process across each institution, looking at neurology, neurosurgery and a number of other specialties that would be involved in a procedure like this.

I will say that we don't see it as a bottleneck because we're doing everything that we can to work with these institutions ahead of a potential BLA approval to make sure that at the point of that BLA approval, we're able to move forward as quickly as possible. There are a number of centers that are available to do this, and we are working with what we think is the right number in the initial term, and then we will continue to build from there.

From a capacity point of view, it's very challenging to give you one number, and we're still working through that because it depends on the number of neurosurgeons at a particular hospital. It depends on the number of intraoperative OR suites and other competing priorities. But we're working through this, and we will plan to share more details around that in the coming months.

Your next question comes from the line of Paul Matteis with Stifel.

This is [ Matthew ] on for Paul. Congrats on all the progress. I guess based on your interactions with the FDA so far, are you expecting an AdCom meeting for this BLA submission? And then separately, I understand you had some studies on patients' low striatal volume and potentially shorter neurosurgical administration. What's the progress on those? And when might we see data from those cohorts?

Thanks, Matthew.

As I mentioned -- go ahead, Walid.

Sorry, Matt. So regarding the AdCom, I think our expectations is that we most likely will have one. We welcome it, and we are preparing for it. Regarding the low striatal volume cohort, that cohort has been fully recruited, but it's a bit early right now to share any of the efficacy data. We've recently shared some of the safety data. So this is moving forward, we will be updating you as the data mature. In terms of the shorter surgical, there's no -- we don't have an ongoing cohort focusing on that at this point, although this is a key element for us that we're going to be thinking about acutely as we're moving forward.

Your next question comes from the line of Luca Issi with RBC Capital Markets.

Team, this is [ Shelby ] on for Luca. Maybe on the regulatory setup for Huntington's. I appreciate different indications, but the recent FDA briefing documents ahead of AdComs for Capricor and Replimune did raise some pointed questions about the efficacy of both drugs. Does the tone of those documents give you any pause that the FDA could still push back on AMT-130 even with the 3-year data agreed upon as the primary basis for the BLA? Any color there, much appreciated.

Yes. Thanks for the question. I mean, obviously, we're aware of the AdComs going on this week, and appreciate that those are serious diseases. But it's not appropriate for us to comment on those particular AdComs. I mean we -- from our perspective, each program is evaluated on its own merits, on its own data and its own patient population. I think it's possible that the FDA may request an AdCom. This would be the first disease-modifying treatment for Huntington's disease. We continue to feel like our interactions with the FDA have been constructive and productive. And in the end, our view is that the data speaks for itself, and we would very much look forward to the extent that there's an AdCom in participating and having that discussion.

Your next question comes from the line of Salveen Richter with Goldman Sachs.

This is Lydia on for Salveen. Just on the regulatory side, again, if you could provide any more kind of color on the ongoing discussions, particularly around the standard of care control arm and how that might impact recruitment and retention in the study given the somewhat open-label nature of that?

Walid, do you want to answer that one?

Sure. Thanks, Matt. Yes, I think the study design is straightforward. So patients would be randomized to either receive treatment or be on the standard of care arm, where they are allowed to receive whatever is the latest standard of care available to them in their geography. I think it's a fair question that you asked in terms of retention. We believe that in our case, there's going to be a couple of items that are going to be paying attention to. One is that people who would be randomized to standard of care will be eligible to receive AMT-130 at the -- after 3 years.

They don't have to meet the inclusion criteria anymore. As long as it is safe to administer it to them, they will be able to receive it. Now of course, if the AMT-130 becomes available to them earlier because it's commercially available, that's going to also depend on our strategy, which I alluded to earlier. The earlier part of the study, we will be prioritizing the U.S. recruitment. But later in the study, we will be focusing on countries where AMT-130 would not be yet available by the time we complete the study so that we can minimize this.

Last but not least, any long-term study will always have a risk of a dropout rate. And we will be using statistical techniques and in agreement with the agency about how we will deal with those dropouts. So overall, we do feel very confident that we'll be able to recruit the study and execute it in such a way that we can draw conclusions on it. And I think this is bolstered by the fact that patients with Huntington's disease actually are amazingly dedicated to being part of studies and actually generating these data, not just for them, but also for their family and their community. Thank you.

Your next question comes from the line of Ellie Merle with Barclays.

This is [ Jasmine ] on for Ellie. So is your current expectation still that you will get priority review? And just following up on this, can you give some more detail on the ways that you're preparing to move quickly to have the confirmatory trial well underway at the time of approval? And how long would you potentially expect enrollment in the confirmatory trial to take?

Yes. Thanks, Jasmine. I'll take the first part of that question on the priority review and then hand it over to Walid to talk about the confirmatory. So just as a reminder, AMT-130 has breakthrough therapy designation and RMAT designation and Fast Track designation. Normally, the priority review would be requested at the time of the BLA submission and the FDA would grant that or not at the time of the acceptance. But given the unmet need here, we think that there's a reasonable chance that, that would be accepted by the FDA. But ultimately, that's to the FDA's discretion. On to you, Walid.

Thanks, Matt. So regarding confidence in the study conduct, I think we prepared for this. We're working diligently with -- within ClinOps to be able to do that. And I'm very confident that we'll be able to recruit it in time. In terms of the size, it's premature to talk about it. As I mentioned, we are still in discussion with the FDA in terms of finalizing the study design, and that will also have, of course, an indication about the sample size. And so once we do that, we'll be able to communicate and we'll be able to give you a better idea about the time line it will take us to recruit this trial.

Your next question comes from the line of Uy Ear with Mizuho.

Congrats on all the progress. So I guess on my first question, could you just clarify, I just want to make sure I understood correctly, whether the accelerated approval is dependent on completion of enrollment for the confirmatory study? If you don't complete, does that mean you don't get the accelerate -- or the application won't be approved or will be held until it's completed? And the second question is, could you maybe just provide -- walk us through the assumptions behind your 2030 cash [ way ]? Like what does that include exactly?

Yes. Thanks for the questions. I'll handle the first question and then pass it over to Christian for the second question. So I mean, just to understand, the FDA put out draft guidance in January of 2025. That draft guidance is for all accelerated approvals and addresses confirmatory studies. And the FDA's intent for all confirmatory studies is really to make sure that they can be completed in a timely manner post approval, right? Accelerated approval is -- you don't have to complete the study to get accelerated approval.

But the FDA wants to ensure that the study can be completed in a timely manner. And I think as Walid said, we feel very confident that we'll be able to do that. Number one, we feel confident we can operationalize the study very quickly. Number two, we believe that we'll be able to focus on the U.S. and pre-approval and to ensure that we have representation from the U.S. Third, this is going to be a global study where we're going to have sites in a number of different countries where the products are not commercially available. So we feel very confident that we'll be able to complete the study in a timely manner to address the FDA's priorities as it relates to confirmatory studies. And with that, I will pass it on to Christian.

Thanks, Matt. Yes, the guidance into 2030 includes a number of things. So first and foremost, enrolling the confirmatory trial, funding the confirmatory trial into 2030, funding commercial launches as well as the ongoing clinical trials as well as making potential investments to advance certain other pipeline candidates into late-stage development.

Your next question comes from the line of Joseph Thome with TD Cowen.

Can you review with us maybe how the SAP for the 3-year data has changed at all over the past year since we saw the September data from last year and your level of alignment with the FDA on that for the final submission? And then maybe relatedly, with the June 30 cutoff date and the September data presentation for the 4-year data, is that just how long it takes to lock and clean the database? Or is there any SAP alignment that's kind of gating for that readout as well?

Okay. Yes. I'll pass that on to Walid. But just to confirm your first question, you're talking about -- have there been any changes to the 3-year SAP?

Yes.

Okay. Yes. So Walid, why don't you answer? I think the question was, have there been any adjustments to the 3-year SAP? And then the second part is questions around the 4-year analysis.

Yes. So the 3-year SAP has not changed since we submitted it to the FDA in July of 2025. Based on that SAP, we shared with you the data back in September of 2025. So that has not changed. Actually, there should be no reason to change it after the fact.

With regard to the 4-year analysis, the time lines are generally similar to what we've done for the last year -- for last year. So we're on track to be able to share the results with you in September of this year.

Great. Maybe just a related follow-up. I guess, has the FDA signed off on that SAP used last year in the most recent meeting? I guess what level of communication do they give you on, yes, this is the SAP we agree with? Or do they not comment to that level?

So just to get back to the history a little bit. So we met with the FDA back in April of 2025, a month after we submitted the briefing book for the SAP. And the FDA at the time provided comments to us, which we incorporated in the SAP that we ultimately finalized and submitted to the FDA in June of last year. There's been no formal communication with the FDA since on that SAP.

And we would not expect it. And that's -- these are the data that form the basis of the analysis and the FDA is aware of those data. And in the recent discussion with the FDA in the recent Type B meeting, we aligned with them that the data from the 3-year analysis -- from the 3-year data cut supports the BLA filing. So that is what we're moving forward with.

Your next question comes from the line of Yanan Zhu with Wells Fargo.

This is [ Jeff ] on for Yanan. So following receipt of the Type B meeting minutes, how closely did the written feedback align with your interpretation of the discussions? Were there any areas of clarification or any points that differed from your initial takeaways? And separately, I believe I heard that total functional capacity at 3 years could serve as the primary endpoint for the confirmatory trial. Given that AMT-130 had about 60% slowing of TFC in the Phase I/II study at 3 years, could you talk about the efficacy bar for the confirmatory trial? Is there any magnitude of TFC benefit that you believe could be required for -- to support full approval?

Yes. I'll take maybe the first question. And then Walid, you can talk about the second question, understanding that we haven't completed the alignment around the confirmatory study. But nevertheless, on the first question, yes, we confirm that we received the final meeting minutes. And I think really, all I would say is that our disclosures in this press release are complete. And so there is no material differences in our interpretation from the disclosures that we've had today. On the second question, Walid, you can go ahead and answer that one.

Yes. Thank you. So in terms of the magnitude effect of TFC, indeed, as you saw in our top line from the 3-year data analysis last year, the TFC changes were 60%. In the confirmatory trial, we will be using that information. Actually, it will be complemented with the updated 4-year analysis because if you recall, we have 3 more patients that would have reached the 3 years in that analysis. So we will have a total of 15 patients that of the 12 that we reported on last year, and we'll be using those to fine-tune the powering.

There's been no discussion, as Matt indicated, with the FDA yet on the details of that study and the powering specifically. We had a proposal, but it's premature for us to be able to talk about it at this point before we reach agreement with the FDA.

Your next question comes from the line of Kristen Kluska with Cantor.

Just to follow up on that point. Curious why the FDA is considering TFC as the primary endpoint over cUHDRS and if that's going to influence how they're going to review the package coming up while recognizing that you also had positive benefits on that endpoint.

Yes. I think -- I mean, this is not a surprise to us at all. And we disclosed back in 2024 that the FDA views the composite unified Huntington's disease rating scale as an intermediate clinical endpoint that is reasonably likely to predict efficacy. Our sense is that the FDA, just philosophically, they look at composites as a number that in and of itself has value, but it's not as valuable or as pure, for lack of better words, as a functional endpoint.

Total functional capacity is a measure of independence. It has a lot of aspects that are quality of life associated. And our sense is that in discussions that the FDA had with us as well as other sponsors that they tend to lean more towards total functional capacity as a primary endpoint for a confirmatory study. But in terms of an accelerated approval, the FDA is comfortable that the composite UHDRS is an intermediate clinical endpoint that is reasonably likely to predict efficacy or therapeutic benefit.

Your next question comes from the line of Suzanne van Voorthuizen with Kempen & Company.

Maybe assuming approval looking at the commercial launch, it's a first of its kind potentially. So can you elaborate a bit higher level on some key characteristics of this upcoming launch that you believe we should consider when thinking of proxies or example launches, speaking of things like the features of the treatment modality, the specifics of the indication or the setup of care centers, et cetera?

Sure. Thanks for the question. Kylie, do you want to go ahead?

Yes, absolutely. Thank you very much for the question. So I think some of the characteristics that are going to be key launch criteria is on ensuring that we have the right number of treatment centers set up and ready to go and able to treat patients.

I think this is obviously going to be one of the key criteria, which is why we've spent so much time engaging with the treatment centers, understanding the specialties that will be relevant within and ensuring we understand the processes as we were discussing earlier. I think this is something that will be a key priority leading up to launch and then obviously post launch.

I think in addition to that, making sure that we have the right engagement on a payer level, making sure they understand the unmet need in Huntington's and the value that AMT-130 can potentially bring and then also ensuring that we understand the patient care pathways, how they're referred and how they're managed and the patient journey in totality. Understanding these 3 components will be critical to how we see launch success.

You asked a little bit about analogs and other ways that would be consistent from a modality point of view. I think as we think about a treatment that is completed through a hospital procedure, I think ZOLGENSMA is a reasonable analog. Also, if you look at ELEVIDYS from a general understanding of capacity point of view, I think they're reasonable analogs, but I will caution that no analog is perfect.

And I think every disease and every treatment space is a little bit different in the way the dynamics work, and we're looking to really ensure that we have all of our I's dotted and our T's crossed when it comes to launch preparation to bring this therapy to Huntington's patients.

Got it. And maybe just a small follow-up. I know that Huntington's is a core focus, but I'm wondering for epilepsy and Fabry, you've reported some encouraging data for both this year. Can you shed some color on how you balance your prime focus versus how you go about decision-making and resource allocation for the other pipeline programs?

Yes. I think over the years, we've really made it a priority to be very disciplined in how we invest and really to make data-driven decisions. We don't view discontinuing or deprioritizing programs as a failure. We're -- we talk about truth-seeking, and we try to run the experiments to answer questions.

And when the data supports moving a program forward and advancing it, we want to do that and focus on impeccable execution. When data does not support moving the program forward, we're also happy to discontinue or deprioritize. We recently did that with our SOD1-ALS program. We've done that in the past, and that's going to be how we continue to make capital allocation decisions going forward.

[Operator Instructions] Your next question comes from the line of Patrick Trucchio with H.C. Wainwright.

This is Arabella on for Patrick. I was just wondering, should we expect a prespecified interim analysis built into the confirmatory study? And if that was positive, say, at 2 years, could that support conversion to full approval prior to the 3-year primary? And then also, do you have any other outstanding CMC items to work on before you can submit the BLA?

Yes. Maybe I'll answer the first question and hand it over to Walid, understanding that we have not completed our discussions with the FDA on the confirmatory study. But on the CMC, we feel confident that we've completed the activities that are required for the BLA submission. Obviously, there, we need to complete Module 3 for the BLA submission. But the fundamental activities around PPQ, validation of analytics and assays, that work, we feel very comfortable that we've done what's required to be ready for the BLA submission. Walid?

Okay. So regarding the prespecified interim, it's really premature to discuss this. We haven't gone to that level yet with the FDA. I think it's a consideration that we should -- it should be part of it, but we haven't yet finalized it, so I really cannot discuss more. So hang tight, more to come once we have that clarified.

Your next question comes from the line of Rudy Li with Wolfe Research.

Given that you already reached agreement on the filing package, what do you think could be the key questions and the debates to be discussed at the upcoming AdCom meeting? Do you imagine any pushback from FDA? And secondly, it sounds like we don't expect enrollment of the confirmatory study to be a key limiting factor to get approval. So I just want to confirm.

Sure. I didn't catch the last part of that, but just -- yes. I mean, I wouldn't want to speculate on what's going to be the content or the FDA's position of an AdCom meeting that hasn't yet been requested. So I don't know how helpful that would be there. And then can you just repeat the second part of the question?

Yes. Second part is really about do you expect enrollment of the confirmatory study to be a key limiting factor to get approval?

Well, I think, I'll repeat what I said before. I think the FDA -- accelerated approvals are conditional approvals. And I think the FDA considers that flexibility because of these critically high unmet needs for Huntington's disease and other indications. But the confirmatory studies are important. And as I said, their fundamental focus is ensuring that they can be completed in a timely manner. And -- but the reality is they have wide discretion to do that.

I mean this is not the first time that the FDA has contemplated a confirmatory study. And I think we feel very confident that we can operationalize the study expeditiously that we can demonstrate to the FDA that it is well underway and demonstrate to the FDA that we've got the infrastructure to complete it in a timely manner. So I think it will be a factor, but I think we feel confident that we can get the FDA comfortable on those key elements.

Congrats on the progress.

Thank you.

This concludes the question-and-answer session and our call today. Thank you all for joining. You may now disconnect.

Thank you for standing by. My name is Liz, and I'll be your conference operator today. At this time, I would like to welcome everyone to the uniQure First Quarter 2026 Earnings Call.

[Operator Instructions] I would now like to turn the call over to Chiara Russo, Senior Director of Investor Relations. Please go ahead.

Good morning, and thank you for joining us for uniQure's First Quarter of 2026 Earnings Call.

Earlier this morning, uniQure released its financial results for the first quarter of 2026, and our press release is available on the Investors and Media section of our website at uniqure.com. Our 10-Q was also filed with the SEC earlier today.

Joining me on the call this morning are Matt Kapusta, Chief Executive Officer; Dr. Walid Abi-Saab, Chief Medical Officer; Kylie O'Keefe, Chief Customer and Strategy Officer; and Christian Klemt, Chief Financial Officer. After our formal remarks, we'll open the call up for Q&A.

Before we begin, 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 conference call. 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 most recent SEC 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 if new information becomes available in the future.

Now let me introduce Matt Kapusta, uniQure's CEO.

Thanks, Chiara. Good morning, and thank you for joining us today.

During the first quarter of 2026, uniQure remained focused on advancing AMT-130 to patients, while continuing to execute across our broader pipeline. Following our Type A meeting with the FDA in January, we acknowledge the agency's feedback and remain focused on engaging constructively defined feasible path forward. We have since been granted a Type B meeting with the FDA later this quarter, where we plan to discuss our proposed statistical analysis plan for the 4-year data expected in the third quarter and key elements of a new clinical study.

In parallel, we are progressing toward a potential regulatory submission in the United Kingdom. Following a successful pre-submission meeting with the U.K. MHRA, we are preparing to submit a marketing authorization application in the third quarter based on the 3-year data. Taken together, these efforts reflect our commitment to advancing AMT-130 globally with urgency.

Beyond Huntington's disease, we continue to make progress across our pipeline. For AMT-260 in refractory mesial temporal lobe epilepsy, enrollment in our Phase I/IIa study is on track, and we expect to report data from the first cohort in the second quarter.

In Fabry disease, updated data from our AMT-191 program showed sustained and dose-dependent increases in alpha-GalA activity, stable lyso-Gb3 levels and the discontinuation of enzyme replacement therapy in 11 patients, supporting the potential of AMT-191 as a meaningful treatment option.

Regarding AMT-162 in SOD1-ALS, we announced our decision to discontinue development following a comprehensive review of the available data, reflecting our disciplined data-driven approach to capital allocation.

Looking ahead, key milestones include our Type B FDA meeting later in the second quarter, clinical update for AMT-260 in the second quarter, 4-year AMT-130 data analysis in the third quarter and the planned MAA submission for AMT-130 in the U.K. in the third quarter. We believe these milestones represent important opportunities to advance our programs and demonstrate the potential of our platform.

In summary, we are executing with focus, advancing our lead program through important regulatory interactions and managing our strong balance sheet to support our long-term strategy. We remain committed to delivering on the promise of gene therapy for patients and creating durable value for shareholders.

With that, I'll turn the call over to Walid to provide more information on the pipeline.

Thank you, Matt. Good morning and good afternoon, everyone.

I'll start with AMT-130 in Huntington's disease. As Matt noted, we continue to engage with the FDA and have a Type B meeting scheduled for later in the second quarter. Our goal is to work through the key design considerations for a potential new clinical study, addressing the agency's concern for an adequate and well-controlled trial while also ensuring the approach is practical, feasible and appropriate in a rare, slow progressing neurodegenerative disease. Huntington's disease is supported by one of the most robust natural history resources in rare diseases. Enroll-HD includes more than 30,000 participants and provides high-quality, longitudinal clinical data collected over many years through the extraordinary efforts of the Huntington's disease community.

We believe this body of real-world evidence can inform efficient and statistically rigorous study designs, and it should be considered as we evaluate with the agency the appropriate design of an adequate and well-controlled study for a onetime administered therapy. Additionally, we plan to solicit feedback on our statistical analysis plan for the 4-year Phase I/II study data expected in the third quarter.

Turning now to our ex-U.S. regulatory efforts, we held a successful pre-submission meeting with the U.K. MHRA earlier this quarter. Based on this interaction, we plan to submit the marketing authorization application for AMT-130 in the third quarter of this year, supported by our 3-year clinical data analysis. This is an exciting potential milestone for uniQure and the Huntington's disease community as we look to bring AMT-130 to patients around the world. We have also started engaging with regulatory authorities in Europe and are evaluating additional opportunities internationally to potentially bring AMT-130 to patients as quickly and efficiently as possible. Finally, we expect a manuscript for our complete 3-year analysis to be submitted in a peer-reviewed medical journal this year.

Moving on to the rest of our clinical stage pipeline, starting with AMT-260 for temporal lobe epilepsy. We continue to collect data on the fully enrolled first dose cohort, which included those with both nondominant and dominant hemisphere MTLE, and we plan to provide an update later in the second quarter on all 6 treated patients with at least 6 months of safety, tolerability and seizure frequency outcomes. These are expected to be presented at the Epilepsy Foundation Pipeline Conference in Leesburg, Virginia in June of this year.

Turning to AMT-191 for the treatment of Fabry disease. In February, we reported preliminary safety and exploratory efficacy data from 11 patients in the ongoing Phase I/II trial of AMT-191. As of January 8 of this year, the study cutoff date, all 11 patients across 3 dose cohorts demonstrated elevated alpha-GalA enzyme activity that was dose-dependent and durable over the observed follow-up period, ranging from more than 1 year in the longest follow-up patient at the high dose to 4 months in a patient treated at the mid-dose. Stable plasma lyso-Gb3 levels were maintained post dose across all dose cohorts regardless of enzyme replacement therapy status. As of February 18 of this year, all 11 dose patients have discontinued ERT.

On safety, as previously reported, 2 patients in the mid-dose cohort experienced asymptomatic Grade 3 liver enzyme elevations. These events met protocol-defined criteria for potential dose-limiting toxicity and were reviewed and confirmed as such by the independent data monitoring committee. Accordingly, dosing at the mid-dose and high doses were paused per protocol. To-date, no new AMT-191 -related serious adverse events have been observed. The program continues to demonstrate a manageable safety profile.

Lastly, there's AMT-162 for SOD1-ALS. As previously disclosed, the Phase I/II EPISOD1 trial of AMT-162 for SOD1-ALS has been on voluntary recruitment pause based on an independent data monitoring committee recommendation after a serious adverse event of dorsal root ganglia toxicity in one patient in the second cohort. This event was determined to be related to AMT-162.

Following review of the preliminary efficacy and safety data generated from EPISOD1, the decision was made to discontinue development of AMT-162. We will continue to collect follow-up safety from the 5 patients dosed, consistent with applicable safety and regulatory requirements.

Now I will turn the call over to Kylie, to discuss our ongoing work with the HD community and our ex-U.S. commercial efforts. Kylie?

Thank you, Walid. Before I turn to AMT-130, I want to take a moment to acknowledge the Huntington's disease community, the patients, the families and the caregivers who live with this disease every day, and the researchers, clinicians and advocates who have spent decades refusing to accept the status quo. Their resilience and their trust in us is not something we take lightly. It is what holds us accountable to the progress we are here to discuss today. We remain committed to continuing the efforts in the U.S. and globally to advance AMT-130 as responsibly and efficiently as possible.

We are encouraged by the path ahead in the U.K. following our recent engagement with the MHRA and are advancing commercial preparations across several key geographies based on this progress. Our market preparation efforts have centered on 3 near-term priorities. First, ensuring treatment center capacity and readiness and working closely with the multidisciplinary care teams at the centers of excellence that will be critical to success. Secondly, in parallel, ongoing patient engagement is critical to maintain continuity across the care journey, supporting genetic testing and referral pathways. Thirdly, market access readiness is advancing, including proactive payer engagement and development of a clear evidence-based value proposition. This is underpinned by robust health economics and outcomes research, generating data to demonstrate long-term clinical benefit and broader societal impact to support pricing, access and adoption.

We believe the U.K. unlocks a meaningful opportunity for uniQure to deliver a potentially transformational therapy to patients with HD, a community with no approved disease-modifying therapies today. There are between 7,000 to 8,000 patients living with HD in the U.K., with approximately 30,000 at risk. The U.K. has world-renowned neurosurgical capabilities and several leading HD centers of excellence, which we believe will be instrumental partners in making this potential therapy available to patients.

Importantly, an MHRA approval will not only enable access in the U.K., we believe it could also enable early access or named patient programs in other geographies, including the Gulf countries in the Middle East, Latin America, Commonwealth of Independent States and Central and Eastern Europe, enabling access to therapies ahead of formal reimbursement decisions, offering hope to patients and families, while local regulatory and broader market access processes continue. We believe this disciplined approach helps drive building a scalable global strategy to maximize the long-term value of our program for all stakeholders.

Moving to AMT-260, in mesial temporal lobe epilepsy, where many patients remain completely refractory to antiseizure medications, cycling through treatment after treatment with no meaningful seizure control. For those who do progress to surgical intervention, the options currently available are at its core, a tissue destructive procedure. We believe being able to deliver a precisely targeted gene therapy in MTLE without destroying healthy tissue may represent a new treatment paradigm.

Lastly on AMT-191. In Fabry disease patients, they face a relentless multisystem disease burden, all driven by a single genetic defect in GLA. The current standard of care, which is biweekly enzyme replacement therapy requires lifelong intravenous infusions that are logistically burdensome and has an occurrence of high rates of neutralizing antibody development, which limits efficacy over time. A single administration therapy correcting the enzymatic deficiency at the genetic level in Fabry, we believe has the potential to meet this unmet need.

Across our customer-facing functions, we're focused on delivering strong execution while being disciplined in scaling the infrastructure needed to support commercial activities with a focus on strengthening center of excellence relationships, refining the patient and provider journey and continuing to build the evidence required for access and adoption.

As we continue our efforts in the U.S., we're also energized by the potential opportunity ahead in the U.K. and other geographies, and are advancing towards an expected MAA submission and the possibility of bringing the first potential disease-modifying treatment for this devastating disease.

Now I'll turn the call over to Christian for a financial update. Christian?

Thank you, Kylie. I'll be sharing the financial highlights of the first quarter of 2026. Please refer to the earnings press release issued this morning and our quarterly filing with the SEC for additional details.

Revenue for the 3 months ended March 31, 2026, was $3.6 million compared to $1.6 million in the same period 2025. The increase of $2 million is due to an increase in license revenue.

Research and development expenses were $29.2 million for the 3 months ended March 31, 2026, compared to $36.1 million during the same period in 2025. The $6.9 million decrease was driven by a $2.6 million decrease in fair value of contingent consideration, a $1.2 million decrease in costs related to external program spend, a $1.6 million decrease in employee and contractor-related expenses, including share-based compensation, and a $1.6 million decrease in facilities and other expenses compared to the prior period.

Selling, general and administrative expenses were $20.1 million for the 3 months ended March 31, 2026, compared to $10.9 million during the same period in 2025. The $9.2 million increase was primarily related to a $5.5 million increase in employee and contractor-related expenses, including share-based compensation, mainly as a result of employees recruited in 2025 to support commercial planning for AMT-130, $1.8 million increase in professional fees, $0.6 million increase in intellectual property fees, and $1.3 million increase in information technology costs and other expenses compared to the prior period.

Cash, cash equivalents and investment securities totaled $586.6 million as of March 31, 2026, compared to $622.5 million as of December 31, 2025. We believe that uniQure continues to be well positioned to execute on its clinical and operational priorities through 2026. We expect that cash, cash equivalents and investment securities will be sufficient to fund operations into the second half of 2029.

I'll now turn the call back over to Matt.

Thank you, Christian. To summarize, our top priority remains continued engagement in the U.S. and internationally to advance a clear and viable path forward for AMT-130. In parallel, we are executing across our pipeline and maintaining a strong focus on capital allocation to support long-term value creation. With several important milestones ahead in '26, we look forward to updating you on our progress.

With that, we will open the call to take questions from our research analysts. Operator, please proceed.

[Operator Instructions] Your first question comes from the line of Moritz Reiterer with Guggenheim Securities.

This is Moritz on for Debjit. I have 2. The first one is around AMT-260. And could you just give a little bit more sort of an overview of what the expectations are for the upcoming data set in June?

I have a follow-on question about AMT-130, namely around the competitor PTC data that was published last week, we noticed that their natural history control was an order of magnitude smaller than what you used for AMT-130. So just trying to understand a little bit better what was the rationale for choosing such a large control cohort? And what are the potential upsides and downsides of that choice?

So on AMT-260, we are conducting a Phase I/II trial. As you know, the primary objective of that trial is to evaluate safety, of course, we're looking at efficacy endpoints, particularly seizure frequencies as measured by diary, in addition to a number of other endpoints. So what we're looking is to identify a dose that's safe and well tolerated based on these data. And we expect to see a signal on reduction of seizure frequency. We're targeting at this stage, perhaps a 50% reduction in seizure frequency could be a good signal for us to follow-up in subsequent well-controlled studies.

In terms of AMT-130, it's really very difficult to essentially compare or interpret results from competitors. We're not in a position to do that. We don't quite know the details of the analysis plan they've done in using Enroll-HD and why the control numbers are low. So I will withhold any interpretation on these data.

Your next question comes from the line of Paul Matteis with Stifel.

This is [ Emily ] on for Paul. We wanted to ask a little bit more about the U.K. market dynamics. And maybe if you could share any color. And another question would be like of the 7,000 to 8,000 patients in the U.K., how many of those are treated at centers of excellence currently?

So maybe starting with the second part of the question. The vast majority of the patients that we alluded to, the 7,000 to 8,000 are treated at specialized centers. There is a collection of those patients that are managed by the specialized centers around the U.K. So that is the vast majority.

Maybe just some other color from that perspective around U.K. market dynamics, I think, once we are able to secure MHRA approval, we obviously work with NICE and a number of the access bodies, including NHS England, to work through managed access agreements to be able to bring the product to market. So that's work that has already started and is ongoing and we'll continue through a potential MHRA approval to bring this product to market.

Your next question comes from the line of Joe Schwartz with Leerink Partners.

Congrats on your progress and persistence. I'd like to ask a question each about your ex-U.S. and U.S. aspirations. First, how aligned do you expect the U.K. and broader EMA review processes to be? And what is your assessment of your ability to receive adequate reimbursement in these territories outside the U.S., which may be more constructive on approval at this point?

Second, what specific feedback from the FDA are you hoping to clarify or potentially challenge in your Type B meeting? How are you preparing your briefing package to make your case?

Do you want to start with the first one, Kylie?

Yes, absolutely. So just talking through ability to secure reimbursement in markets outside of the U.S. So I think the aim is to start with named patient and early access programs that give us an ability to be able to secure patients very rapidly post approval. We will also progress with formal pricing and reimbursement negotiations.

I think one of the things that we're definitely seeing is the U.K., in particular, is a market at an inflection point. They've really tried to look at how to bring advanced therapies to market, and they've tried to shift their thinking, for example, bringing in the highly specialized technology route and other aspects of raising the QALYs and ISA considerations. And so this is really trying to ensure that they're bringing advanced therapies to patients in the U.K. and not being left behind.

Outside of the U.K., we'll be taking a very specialized approach. We'll be assessing markets on a market-by-market basis, looking at funding pathways, looking at access to therapies and ensuring we're doing this in a step-by-step approach rather than more of a simultaneous approach. And so that will be taking reimbursement as a primary consideration into focus.

Walid, I'll take the second question. Thanks, Joe. So in terms of the meeting with the FDA, we view this as a technical meeting. Our hope is to gain some clarity on key design elements of an additional new study to evaluate the efficacy of AMT-130 and also to get feedback on the statistical analysis plan for the 4-year data.

Next question comes from the line of Salveen Richter with Goldman Sachs.

Can you speak to your base case assumption for the Phase III study design of AMT-130 and whether Novartis' recent study is a precedent here? And then separately, just frame expectations for the 4-year data in the third quarter and what sensitivity analyses these might include.

So in terms of design elements of a new study to evaluate clinical efficacy, we can't really go into details because it depends on the discussions with the agency. We genuinely want to have a constructive discussion with the agency. Our position is that in this rare slowly progressing disease, where we have a onetime therapy administration and when there is a treasure trove of natural history data that we could use, we should be looking at potential flexibility in trying to utilize these resources to minimize the burden on the patient and make these studies rigorous, but still feasible. And then that is truly our goal in the meeting.

Regarding the analysis of the 4-year data, in broad terms, they're actually going to be generally similar to the 3-year analysis with the addition, of course, of 1 more year of follow-up, which will bring the total number of patients at 4 years to 12 at the high dose and 12 at the low dose. In addition, there will be 3 patients at the high dose, who would have completed 3 years, so making 15 patients who have reached a 3-year analysis at the high dose.

We are discussing with the agency whether there could be additional potential analyses that they would want to see in order to increase the level of confidence. Our expectations are that with time, treatment effects will become more and more evident and the absolute difference between those treated with AMT-130, particularly on the high dose, is going to become much more evident when compared to well-matched external controls.

Your next question comes from the line of Yanan Zhu with Wells Fargo.

This is [ Kwan ] on for Yanan. So also on Huntington's disease, you mentioned in the Type meeting, you talked about design of the new study and 4-year data statistical plan. Can you talk about, will you also cover the potential of an alternative regulatory path? And is there still a possibility to file without starting a new study?

The purpose of the meeting, as I said previously, is technical in nature to discuss elements of the design for a new additional study to evaluate the efficacy and also the 4-year analysis. We do not intend to have a specific discussion about a regulatory path to filing at this point.

Your next question comes from the line of Peyton Bohnsack with TD Cowen.

This is Peyton on for Joe. I guess kind of looking at the U.K. commercial opportunity, can you talk about the number of centers that you've identified in the U.K. that are equipped to do the MRI-guided stereotactic surgery? Are there any planned changes to the surgical procedure in a potential commercial product? Specifically, any changes in the length of the time of the procedure? And does anything need to be done to validate or approve the cannula? That'd be it.

I'll unpack. There's a few elements to answer there. Maybe just starting with the number of specialized centers in the U.K., I think, probably you do know this, but we had a number of centers that were incorporated into our European clinical trial, so there are a number of centers that have already treated AMT-130 patients. But this is just a small handful of the number of centers that exist in the U.K. that have neurosurgical stereotactic capabilities. And so we have already identified a number of those and have engaged with them to start to really plan the market in the U.K.

The second aspect of the question was related to changes in the procedure. So from that perspective, we don't anticipate any changes in the procedure transitioning from a clinical program into a commercial program. We expect it to be consistent with what was done in the clinical trials. And so from that perspective, no changes there.

The third part of the question was whether or not we see any challenges in getting the cannula into the U.K. -- and no challenges there. The cannula has been shipped to a number of different countries around the world and the U.K. is no issue there, including through clinical trials and through commercial aspects. We are not the only company that utilizes the cannula. And so there are already commercial companies that are utilizing the cannula in the U.K.

Your next question comes from the line of Luca Issi with RBC Capital Markets.

Maybe Matt or Walid, kind of bigger picture, can you just maybe compare and contrast the Type A meeting you had in January with the FDA versus the pre-submission meeting you had with the MHRA in the U.K. Again, I appreciate that these are different jurisdictions and different regulatory bodies. But why did the U.K. found your data persuasive versus the FDA did not? Is that because they're more willing to compare single-arm data with like historical control? Is that because they have better appreciation for the unmet medical need? What's driving that dichotomy there? I think any color there much appreciated.

Yes, Luca, it's obviously hard to get into the mind's eye of each of the regulatory authorities. But we've been saying this now for 6-plus months, that we strongly believe in the strength of our data. We've achieved 75% slowing of disease with high statistical significance out to 3 years on the composite UHDRS. We achieved statistical significance in a slowing of disease on total functional capacity. We see favorable trends across other clinical measures, we see neurofilament light below baseline and there's a tremendous unmet need here where there's no disease-modifying treatments for these patients. I think based on the discussion that we had with the U.K., I think they recognized these elements.

Walid, do you want to chime in?

I just want to chime in one piece. I think one of the things that also might be a bit different in the U.K. now is that focus on rare disease has been a policy for the current government. So I think this actually meets with a certain agreement within the overall policy of the government there and actually allows for more flexibility to be afforded in rare diseases like this. We hope that this could also be used in other countries as well, of course, in the U.S., and we continue to work constructively with the FDA to achieve that. At one point, there were more openness and flexibility with us. More recently, it's been a bit more difficult. But again, we continue to work with the FDA. And at the end of the day, the data that we're going to be generating will help hopefully to get us to where we need to go.

Your next question comes from the line of Ellie Merle with Barclays.

Can you elaborate a bit on the range of outcomes for what we could learn from the Part B meeting?

Then a second question. Do you plan to request another meeting with the FDA after the 4-year data to pursue accelerated approval again based on the 4-year data?

I think at this juncture, just with the Type B meeting schedule, we won't speculate on the range of meetings and the range of outcomes. And then based on the discussion that we have, we'll ascertain whether there is a need for another follow-up meeting with the FDA, and we'll certainly provide that as part of our update once we receive the minutes.

Your next question comes from the line of Suzanne van Voorthuizen with Kempen.

For the ex-U.S. strategy, can you elaborate on your current thinking on the commercial launch in Europe beyond the U.K., assuming you're also targeting a potential EU approval? For example, for the sequential rollout, which countries are most likely first to target? And what are dynamics that you see that are similar or different from the U.S., which we should consider when launching 130 for Huntington's?

Then a small one on your cash runway guidance into H2 '29. Can you remind us what parts of your business plan are or are not included in that guidance?

So this is Walid. I'll start with the regulatory strategy beyond the U.K. and U.S. So we are evaluating and we've actually started the process of engaging a number of regulatory authorities, including Europe and outside the U.S. We expect to have an update for you in the second half of the year. That's as far as regulatory.

I'll turn it over to Kylie to talk about the commercial strategy.

As mentioned, from a commercial strategy point of view, we're going to be taking each step as a sort of assessment of country by country. So we're looking at countries that have patient access and early access programs well established, which is a number of countries in Europe that would allow us to unlock treating patients early on in the process as we progress with formal pricing and reimbursement. Obviously, Germany has a well-established pathway with regards to free pricing in the first 6 months for rare disease products. France also has the ATU program or the AP program, which it has now evolved into. And there's a number of other countries, Italy, for example, that has named patient in early access.

So we would look at this on a country-by-country basis and assess the funding pathways and the ability to bring this therapy to patients ahead of formal pricing and reimbursement and take the steps from there.

Yes. Quickly on the runway, it's going to be same assumption as for a couple of Qs that we complete the ongoing clinical trials for TLE, HD and Fabry. To get into the second half of '29 does not allow us to simultaneously take forward all the candidates in kind of the most expedited manner. So there will need to be prioritization decisions if we want to maintain the runway.

Your next question comes from the line of Patrick Trucchio with H.C. Wainwright.

My questions are on AMT-191. I'm wondering what the gating criteria are to resume AMT-191 dosing or select a go-forward dose after the mid-dose DLT. Specifically, I'm wondering what IDMC regulatory steroid prophylaxis or other follow-up criteria are necessary to move forward? And separately, now that we have all 11 AMT-191 patients off ERT, I'm wondering what duration and organ level follow-up are needed to define the next development step.

Per protocol, any time we see a Grade 3 adverse event, that could be potentially a DLT. So per protocol, we stopped dosing. There has been very close collaboration with the IDMC, informing the FDA. The patients are followed very closely and treated with steroid as well as steroid sparing therapies. And one patient fully recovered. The other one is really within a very close to fully recovering. So I'm very pleased with the process. Once that is done, we will submit these data to the FDA for the review and discuss resuming dosing at 1 of these 2 doses. In the meantime, the study is ongoing, and we continue to dose with our low dose of 2x10^13, and we continue to follow the patients.

So at the end of the day, this is a Phase I/II trial. And our goal in this trial is to be able to identify a dose that's safe and well tolerated. We're going to be looking at the totality of the data. If we see these changes in LFTs as we see, as we have observed to what degree we can monitor them and manage them with steroids to what degree they're associated with any other types of data to suggest that there might be autoimmune in nature. We don't see that yet. So at the end of the day, we will pick a dose that is safe and well tolerated based on these data and that will generate a significant increase in alpha-Gal activity, especially when these patients are off steroids.

We will be engaging with the FDA in the second half of the year, I should say, to better understand any potential pathway forward, specifically essentially a pathway that would be similar to what was afforded to Sangamo. And based on these, we will be then making a decision about next steps with this program in the next 6 to 12 months.

Your next question comes from the line of Kristen Kluska with Cantor.

On AMT-130, of the 7,000 to 8,000 patients diagnosed today, what percent or number of them do you think would be potentially eligible for therapy at launch? And then based on your time lines for submission and the fact that they really seem to be pressing with this policy for rare diseases, when would you ultimately expect an approval decision?

I can take the first part of the question, and then Walid can take the second one.

From a percent eligible perspective, I think it's a little bit premature for us to put a point on a specific percentage. I think we're working through that at the moment with an understanding of what we think the label could look like because, obviously, that will have a key consideration of percent eligible. But I think as we sort of understand the market in more detail, we'll be able to share more specifics but more to come on that.

So in terms of timing, as you know, for the MHRA, the timing is not as clear as with the FDA in terms of PDUFA date. And that depends because it's variable, that depends on how many rounds of questions you have and the clock stop, which is the time that it will take us to answer those questions. So that also will depend on how many questions, how complicated there are to get answers to.

We will be working, of course, very diligently to move this as quickly as possible. But it's very difficult to give you an exact timing because it all depends on the number, how many rounds of questions as I mentioned.

Your next question comes from the line of Daniil Gataulin with Chardan.

A quick on 130 in the U.K. At launch, if it's approved, what would you expect the capacity to be with all the centers that can administer the procedure?

The second question is, are there countries that recognize MHRA decision for their approval? And how many patients would that potentially add?

So on the first part, which is capacity in the U.K., sorry -- capacity in the U.K., I think, there's a number of centers, as I mentioned earlier, that have the capabilities to be able to do this treatment procedure. So I think it depends on the process that we'll be ensuing from an access point of view. There is the Innovative Medicines Fund that allows you to secure early access and early revenue, and that would unlock some patients. And then obviously, we would need to move through the process with NICE and ultimately NHS England to secure a formal recommendation and managed access agreement to be able to open up a larger potential pool.

So in the near term, I think the capacity is very much where it needs to be. In the longer run, we'll be able to take a deeper look at what does that capacity look like. I think similarly to the U.S., the team is starting to look at the capacity and the pull-through there. And I think from where we stand today, it looks like in the near term, we're in a good position, and then we'll work through what else is needed over the longer run.

From countries outside of the U.K. that reference an MHRA approval, there is a number of countries that do that open up named patient and early access programs. A couple just to highlight from the Gulf countries in the Middle East, Saudi Arabia, UAE as an example, there's a number of countries that we're able to move forward in Latin America, in Commonwealth of Independent States and then also in non-EU, Central and Eastern Europe. So that's just to give you an example of some of the markets that are unlocked through a potential MHRA approval.

[Operator Instructions] Your next question comes from the line of Rudy Li with Wolfe Research.

I think you mentioned that you're not planning to discuss filing at the upcoming Type B meeting. Is it fair to say that the base case scenario will be running a new pivotal trial to support filing?

Secondly, what do you think is the biggest pushback from FDA regarding natural history control? Because I'm still confused why they would require a sham-controlled Phase III instead of a single-arm pivotal trial.

Yes. I think what we know is that -- we have the guidance that we got from the FDA, right, previously, which is their recommendation that we conduct another study. And that's why, obviously, we want to go into the FDA and have a discussion around those design elements.

As I say, this upcoming meeting is an interaction with the review team. And so there are tactical and technical matters that we want to get through that include not only what I just described, but also a review of the 4-year statistical analysis plan. So we're going to continue to follow these patients. And as I said, we believe strongly in the therapeutic potential of AMT-130 and the potential that the data will continue to demonstrate that. I think once we have the data, then we can engage with the FDA and discuss what is the appropriate path forward.

In terms of your question around natural history, again, that's a question for the FDA. I think what we would say is that there's probably no indication that I'm aware of in the rare disease space that has as much natural history data available to leverage. And on top of that, clinical-grade quality, longitudinal data. So to the extent that single-arm studies and external control comparisons are acceptable for intractable diseases with high unmet need, we think there is a strong rationale, particularly given the slow progressing nature of HD, the onetime administrative nature of AMT-130 and the surgical delivery of the product. So I think that's what we would say in that regard.

There are no further questions at this time. Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

Thank you for standing by. My name is Kate, and I will be your conference operator today. At this time, I would like to welcome everyone to the uniQure Fourth Quarter and Year-End 2025 Earnings Call. [Operator Instructions] I would now like to turn the call over to Chiara Russo, Senior Director of Investor Relations. Please go ahead.

Good morning. and thank you for joining us for uniQure's year-end 2025 earnings call. Earlier this morning, uniQure released its financial results for the fourth quarter and year-end of 2025, and our press release is available on the Investors and Media section of our website at uniqure.com. Our 10-K was also filed with the SEC earlier this morning. Joining me on the call this morning are Matt Kapusta, Chief Executive Officer; Dr. Walid Abi-Saab, Chief Medical Officer; Kylie O'Keefe, Chief Customer and Strategy Officer; and Christian Klemt, Chief Financial Officer.

After our formal remarks, we'll open up the call for Q&A. Before we begin, 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 conference call. 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 most recent SEC 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 if new information becomes available in the future. Now let me introduce Matt Kapusta, uniQure's CEO.

Thanks, Chiara. Good morning, everyone, and thank you for joining us on our year-end 2025 conference call. For more than 25 years, uniQure has been driven by a singular mission to deliver transformative medicines to patients living with rare genetic and other debilitating diseases. Along that journey, we have successfully developed 2 approved gene therapies. For the past decade, we have been deeply focused on advancing AMT-130, a novel one-time administered treatment designed to address the underlying cause for Huntington's disease. In September of last year, we reported groundbreaking 3-year data from our Phase I/II study of AMT-130, which were widely embraced by the HD community.

These data demonstrated a statistically significant 75% slowing of disease progression as measured by the composite Unified Huntington's disease Rating Scale, a statistically significant 60% slowing as measured by Total Functional Capacity, a reduction in neurofilament light, a key indicator of neurodegeneration from baseline and supportive trends across other key clinically meaningful endpoints. Importantly, these outcomes were assessed against a carefully and methodically constructed patient-matched external comparator derived from Enroll HD, the largest independent Huntington's Disease natural history data set in existence encompassing longitudinal clinical grade data for more than 30,000 participants that has been rigorously and painstakingly collected over the past 14 years.

While the months since sharing our landmark data have presented certain challenges, they've only strengthened our conviction that AMT-130 has the potential to benefit patients with Huntington's disease and reinforced our unwavering commitment to the HD community. As previously disclosed, during the October 2025 pre-BLA meeting, the FDA conveyed that data submitted from the Phase I/II studies of AMT-130 were unlikely to provide the primary evidence to support a BLA submission. We subsequently held a Type A meeting with the agency on January 30 to discuss next steps. In the meeting minutes we received on Friday, February 27, the FDA explicitly affirmed their commitment to exercising appropriate regulatory flexibility to facilitate the development of safe and effective therapies for HD. Still, the FDA strongly recommended we conduct a Phase III randomized double-blind sham surgery controlled study of AMT-130.

While we respect the agency's perspective and share its commitment to rigorous science, we believe it's appropriate to fully and carefully consider how regulatory flexibility is applied in the context of a rare, monogenic, slow progressive and ultimately fatal neurodegenerative disorder, for which there are no approved disease-modifying treatments. In our view, the totality of evidence generated to date for AMT-130 warrants continued substantive dialogue regarding the most scientifically grounded and feasible regulatory pathways given the severity of the unmet need and the irreversible nature of the disease.

While this was not the feedback we were hoping for, we remain highly confident in the strength and durability of our data. Our focus now is on constructive engagement with the FDA to further define a clear and efficient regulatory path forward. We are actively evaluating the agency's recommendations, including potential Phase III study designs while preserving our commitment to advancing the program responsibly and expeditiously. In addition, we intend to update our Phase I/II statistical analysis plan to incorporate a 4-year analysis that we expect to conduct in the third quarter of 2026. We believe extended follow-up will further inform the durability and magnitude of effect observed to date.

Let me be clear, we remain unwavering in our commitment to the HD community and greatly appreciate their tireless support over the past months and years. The urgency in the community is real, and we strongly believe AMT-130 has the potential to deliver meaningful disease-modifying benefits. Our team is fully engaged in determining the clearest and most efficient regulatory pathways to bring this therapy to patients as quickly as possible around the world, and we look forward to providing further updates as these discussions progress. With that, I will turn the call over to Walid to provide additional color on HD and our other clinical programs. Walid?

Thank you, Matt. Good morning and good afternoon, everyone. I would like to start by reiterating that the recent feedback from discussions with the FDA does not change our mission. We strongly believe that AMT-130 represents the most compelling therapeutic data set generated in Huntington's disease to date and that these results provide the first clinical evidence that gene therapy can potentially alter the course of HD. As Matt noted earlier, we had a meeting where I had a Type A meeting with the FDA in late January. This meeting, we reviewed the previous FDA guidance and discuss key elements of our data package, including the statistical approach, construction of the natural history external control, biomarkers and clinical endpoints.

We also shared with the agency additional sensitivity analyses and discussed additional data generation and considerations regarding the design of a Phase III trial. The official meeting minutes received from the FDA stated they cannot agree that data from the Phase I/II studies compared to an external control are sufficient to provide the primary evidence of effectiveness to support a marketing application. The agency also highlighted the absence of treatment effects relative to sham subjects in the U.S. Phase I/II study after 12 months. We respectfully have a different interpretation of these results than the FDA.

In patients with early HD, 1 year is generally insufficient to reliably detect a meaningful progression of their disease. In the sham controlled portion of our U.S. study, control patients did not show clinical worsening after 1 year, making it virtually impossible to demonstrate any effect over that short period of time for a therapy designed to slow disease progression. To that end, evidence of disease slowing started to emerge in the second year of follow-up and has become even more pronounced in the third year. In rare diseases, where progression is slow, longer observation periods are required to demonstrate an improvement in the disease course. This is often addressed through comparison to well-characterized external controls derived from natural history data sets using statistical methodologies designed specifically for that purpose.

There are multiple precedents where such approaches have supported regulatory approvals. Still, during the recent meeting, the agency strongly recommended we conduct a well-designed Phase III randomized, double-blind sham surgery-controlled study to demonstrate efficacy of AMT-130. We believe that a multiyear sham-controlled study could impose significant risks and burden to patients. Some might even consider it this trial design to be unethical. The HD patient community strongly agree with the sentiment and has communicated directly to the FDA on multiple occasions. These considerations warrant careful evaluation, particularly in the context of a rare, progressive and ultimately fatal neurodegenerative disease.

Importantly, Huntington's disease is supported by 1 of the most comprehensive natural history databases and rare disease. Enroll HD alone includes more than 30,000 participants with high-quality longitudinal clinical data collected over many years through the extraordinary efforts of the HD community. We believe that this body of real-world evidence provides a strong foundation to inform efficient and scientifically rigorous study designs making a long-term sham-controlled study of a one-time administered therapy difficult to justify. We do hope that the FDA will be willing to work with us on ways to leverage this valuable natural history data to design an adequate and well-controlled Phase III study.

We plan to request a Type B meeting in the second quarter of 2026 to further discuss potential Phase III study design in purchase that address the agency's feedback while also considering feasibility and patient risk. Additionally, we intend to amend and submit for review an updated statistical analysis plan for the ongoing Phase I/II study to include 4-year follow-up data compared to an external control. We believe extended observation has the potential to demonstrate continued durability and increased clinical meaningfulness of AMT-130 over time.

Following unsolicited outreach by ex U.S. regulators after our 3-year data disclosure in September 2025, we have initiated regulatory discussions with several agencies. We will continue these discussions throughout the year and we'll provide an update once we have additional clarity on the regulatory pathway. We look forward to the opportunity to potentially bring forward our innovative treatment to patients outside the U.S. in an expedited matter. Meanwhile, we continue to analyze the large body of data we have accumulated with AMT-130. In February of 2026, just recently, we presented at the CHDI meeting in Folgwings, California, a new analysis showing that propensity score methodology using clinical covariants with TRACK HD and PREDICT HD data sets effectively substitutes for baseline stride volume in prediction of Huntington's disease progression.

The Coveris use in these analyses were the same as those used in the 3-year analysis we shared in September 2025 to match AMT-130 patients to their counterparts and the external competitor cohort from the Enroll HD study. We continue to develop a manuscript with the complete results of our 3-year analysis and anticipate publication in the peer-reviewed medical journal later this year. Moving on to Fabry disease. In February, we reported preliminary safety and exploratory efficacy data from 11 patients in the ongoing Phase I/II trial of AMT-191, which was presented at the World Symposium in San Diego, California. As the cutoff date -- as of the cut update on January 8, 2026, all 11 patients in free dose cohorts exhibited elevated alpha-Gal A enzyme activity with 6 patients successfully withdrawn from enzyme replacement therapy.

As of today, I'm pleased to report that all 11 patients have been withdrawn from enzyme replacement therapy. Importantly, dose-dependent elevation in alpha-Gal A enzyme activity were observed across the 3 dose levels. These increases were durable for the measured period of time, ranging from more than 1 year, the longest follow-up patient at the high dose to the shortest follow-up period of 4 months when the patients treated at the middle. Stable plasma lyso-Gb3 levels were maintained those dose across all those cohorts regardless of ART status through the cutoff date. AMT-191 continued to show a manageable safety profile. No serious adverse events related to AMT-191 have been reported in the mid- and low doses. 2 patients at the mid-dose experienced asymptomatic Grade 3 liver enzyme elevation. For protocol, any such grade 3 LFT increases are considered potential dose-limiting toxicity, which require review and confirmation by the independent data monitoring committee.

Following such a review, these events were confirmed as dose limiting toxicity. And per protocol, we have paused dosing at the mid and high doses pending further evaluation. I'm pleased to report that both patients have responded well to corticosteroid therapy and are tapering off steroids with no loss of alpha-Gal A enzyme activity as of today. Turning now to AMT-260 for metal temporal epilepsy. 2025 was a productive year for the program. We shared data from a case study of the first patient treated with MT-160 with up to 6 months of follow-up presented most recently in September 2026 at the International League against epilepsy meeting in Lisbon, Portugal.

Initial data showed a promising reduction in seizure frequency over the first 6 months with no serious adverse events. We have since completed enrollment of 5 more patients in the first cohort and begun enrollment in the second cohort. We expect enrollment to be completed in the second cohort by midyear. Additionally, we plan to provide an update in the second quarter on all 6 treated patients in the first cohort, including those with nondominant and dominant hemisphere lesions with at least 6 months of safety, tolerability and seizure frequency outcomes.

I will now touch base on some additional pipeline updates. Phase I/II episode I trial of AMT-162 for SOD1 ALS remains on voluntary enrollment and treatment hold based on the recommendations of the independent data monitoring committee following a September 2025 review of preliminary data related to the safety and efficacy of AMT-162 in the context of a dose-limiting toxicity that was observed in 1 patient in the second cohort. This event of dorsal root ganglia toxicity resulted in a serious adverse event determined to be related to AMT-162. We will continue to collect data and evaluate data from the patients as they're being accumulated. Now I will turn over the call to Kylie to discuss our ongoing work with the HD community. Kylie?

Thank you, Walid. Starting out with AMT-130 to the Huntington's disease patient community. We want to thank you for your extraordinary strength, resilience and unwavering commitment to advancing disease-modifying therapies for HD. Your courage in the face of daily challenges your willingness to participate in research and your steadfast advocacy are the driving forces behind progress in HD. Importantly, your push for regulatory flexibility for HD through petitions, congressional engagement, direct dialogue with regulators and persistent public advocacy has elevated the urgent needs of families living with HD and we'll continue to do so. .

Your engagement, partnership and determination continue to inspire us here at uniQure. And together, we will keep moving forward. We remain committed to the HD community. And as Matt noted, we remain committed to finding the most expeditious path forward for AMT-130. Over the past quarter, we have significantly expanded our engagement with neurosurgeons, neurologists and multidisciplinary care teams across the U.S. receiving overwhelmingly positive feedback on the AMT-130 data set and its potential to meaningfully impact patients. These discussions have reinforced both the clinical relevance of our data and the strong interest across the HD treatment centers of excellence in advancing this therapy. In parallel, we are actively assessing ex U.S. opportunities, evaluating priority markets based on epidemiology, regulatory pathways, pricing and reimbursement landscape.

In addition, we will be actively pursuing name patient and early access program opportunities in rare disease outside of the U.S. that help enable access to therapies ahead of formal reimbursement decisions, offering hope to patients and families while broader market access processes continue. This disciplined approach ensures we are building a scalable global strategy to maximize the long-term value of our program for all stakeholders.

Moving to AMT-260. We also see significant market opportunity for a potential gene therapy and temporal lobe epilepsy, where a substantial proportion of patients remain drug-resistant despite multiple antiseizure medications and continue to face ongoing unpredictable seizures, that drive injury risk, cognitive decline, psychiatric comorbidities and reduced quality of life. Even with surgical resection or neuromodulation, many patients are not eligible or failed to achieve durable seizure reduction, underscoring the need for innovative disease-modifying approaches that can address the underlying epileptic genetic focus and provide sustained benefit from a one-time intervention.

Similarly, for AMT-191 in Fabry disease, a one-time gene therapy has the potential to address the underlying enzyme deficiency and meaningfully reduce lifelong treatment burden, positioning it to compete in a market currently defined by chronic enzyme replacement therapies and other long-term therapies. Importantly, enzyme replacement therapies require regular lifelong infusions, may be associated with the infusion-related reactions and antidrug antibodies, and often provide incomplete tissue penetration, highlighting the potential advantage of a durable one-time genetic approach.

Overall, our customer-facing team remains intensely focused on disciplined execution today, while thoughtfully building the capabilities, partnerships and evidence base required to drive the long-term success across our full portfolio. Now I will turn the call over to Christian for a financial update.

Thank you, Kylie. I'll be sharing the financial highlights of the full year of 2025. Please refer to the earnings press release issued this morning and our quarterly filings with the SEC for additional details. Revenue for the year ended December 31, 2025, and was $16.1 million compared to $27.1 million in 2024. The decrease of $11 million was primarily driven by a $10.7 million decrease in collaboration revenue and a $6.1 million decrease in contract manufacturing revenues, offset by a $5.8 million increase in license revenues. Cost of contract manufacturing revenues was nil for the year ended December 31, 2025, compared to $17.1 million in 2024.

Following the divestment of the Lex facility in 2024, cost of contract manufacturing revenues are recorded net associated revenue within other expenses. Research and development expenses were $140.7 million for the year ended December 31, 2025, compared to $143.8 million in 2024. A decrease of $3.1 million was primarily driven by a $26 million decrease in total other research and development expenses, $25 million of which related to decreases in employee, contractor related and severance costs as well as facility costs resulting from the 2024 divestiture of the company's Lexington manufacturing operation and organizational restructuring in the same year. This was offset by $22.9 million increase in total direct research and development expenses, of which $19.4 million related to the preparation of a potential BLA submission for AMT-130.

Selling, general and administrative expenses were $65.5 million for the year ended December 31, 2025, compared to $52.7 million in 2024. The $12.8 million increase was primarily driven by a $9.4 million increase in professional fees, including $6.5 million incurred to support the preparation of the planned commercialization of AMT-130 in the United States as well as a $3.6 million increase in employee and contractor-related expenses and a $2.8 million increase in other expenses. This was offset by a $1.8 million decrease in share-based compensation expenses and a $1.2 million decrease in severance costs.

Cash, cash equivalents and investment securities totaled $622.5 million as of December 31, 2025, compared with $367.5 million as of December 31, 2024. The net increase was primarily attributable to proceeds of approximately $404.2 million raised through public offerings of ordinary shares and prefunded loans. With this strong balance sheet, we believe uniQure is well positioned to execute its clinical and operational priorities throughout the coming year. Expect cash, cash equivalents and investment securities will be sufficient to fund operations into the second half of 2026. We I'll now turn the call back over to Matt.

Thank you, Christian. As we look ahead to 2026, our priorities are clear. We are focused on constructively engaging with regulatory authorities inside and outside the United States to define the most appropriate path forward for AMT-130, advancing our pipeline programs with discipline and continuing to generate high-quality data across our portfolio. The strength and durability of our Huntington's disease data set, the progress in Fabry disease and TLE and our strong balance sheet position us well to execute on this strategy.

Most importantly, we remain committed to the patients and families we serve. The urgency in these communities is real, and we believe our gene therapy platform has the potential to meaningfully change the trajectory of devastating diseases. We look forward to updating you as we continue to advance our programs thoughtfully and responsibly. With that, we will open the call to take questions from our research analysts. Operator, please proceed.

[Operator Instructions] Your first question comes from the line of Paul Matteis with Stifel.

This is Julian on for Paul. I guess primarily are there any paths that you can potentially pursue in order to push your agenda beyond just the traditional FDA channels here I'm curious like what other levers you can pull to potentially garner support for registration based on either the existing data or the 4-year data. And then for the 4-year data, can you just confirm whether you plan on submitting that to the agency and whether we can expect the additional handful of patients in the analysis -- in the 3-year analysis as well? Or if you just plan on sharing 12 patients of data at 4 years.

Okay. Yes. I maybe will answer the first part and then Walid can answer the second part. Yes. I mean the other avenues we can pursue are potentially outside the United States, quite frankly. I mean inside the United States, the avenues go through the FDA. I think what we've seen over the last several months is a tremendous amount of advocacy on behalf of the patient community. In my view, that is a critical part of educating and informing elements outside of the FDA around the needs and the sense of urgency within the community. We've also heard from the scientific and clinical community that continue to believe that regulatory flexibility is absolutely required for genetically defined diseases like HD that are neurodegenerative and progress very slowly. .

So to me, that's going to be an essential element of this and then pursuing opportunities where we can bring AMT-130 to patients as soon as possible outside the United States, where there seems to be real interest for regulatory authorities, I think that's what we're going to pursue. On the 4-year data, I can hand it over to Walid.

So on the 4-year data, we informed the FDA that we will be amending the protocol or the SAP specifically to conduct such analysis, and will submit it to them as well. we did not specifically discuss with them what that would mean. Actually, we don't believe that there's any reason we have today to believe that this will change the FDA's position regarding the Phase I/II trials. I need to be clear on that. Having said that, what data will be evaluating it would be essentially presenting the data of the 12 patients at 4 years. but also the -- all the patients who have by then reached would have reached 3 years as well. So we'll be presenting the totality of the data.

I think those data are very important for the HD community and to be able to continue to demonstrate the durability of the effect as well as a potential even a more evident treatment effect of AMT-130.

Your next question comes from the line of Joe Schwartz with Leerink Partners.

So in last week's CNBC interview with Dr. McGarry seemed concerned about the morbidity associated with procedures and involving bur holes, which is what you used with AMT-130. So I'm just wondering, was this a major sticking point? Did it come up in the Type A meeting? Have you done everything possible to educate the FDA on that front? And what is your strategy for the Type B meeting and outside the U.S. to now?

Yes. I mean we don't want to comment directly on what Dr. McGarry said. But just in terms of the interaction with the FDA obviously, they're going to be focused on patient safety. We have, in our view, quite a strong safety profile. We have not seen disease clinical safety events associated with AMT-130 since December of 2022. We obviously saw some safety events that were associated with the procedure. It is a surgical procedure. We also know, as we've disclosed previously that there are some volumetric changes that are as to be expected, those are not associated with any clinical consequences as we've seen, and we see no increases in neurofilament light that would be associated to the extent that those volumetric changes were related to accelerating atrophy. And we've had experts in our recent meetings with the FDA, we've had experts on the call that have talked about volumetric MRI changes.

We've had clinical experts that have seen patients. So we've done everything we can to educate the FDA in this regard.

The strategy for the -- do you want to talk about that?

Sure. So for the Type B meeting, our main goal is going to be to discuss with the agency designs for the Phase III trial. As I said, we believe that we are very fortunate in the space to have a very high grade ongoing contemporaneous natural history, specifically, I'm talking about enrolled HD with more than 30,000 participants. this, what I call a treasure trove that is generally provided to us by CACI and through the hard work of many, many patients and their families and the whole HD community. We think that could deleverage to be able to help us somehow strengthen study designs for Phase III and try to avoid designs that would be difficult and challenging to the patients, so we're looking forward to be working with the FDA on that.

We hope that they will work with us and acknowledge the flexibility they often talk about that should be afforded to rare diseases. That's going to be the key focus of that type of meeting. the second quarter.

Your next question comes from the line of Peyton Bohnsack with TD Collin.

This is Peyton on for Joe. Real quickly, when talking about the Phase III design, how quickly do you think that you would be able to enroll it -- would you be able to use an 18-month endpoint similar to what's been seeing outer in the space? And then has this changed your partnering decisions at RF .

Maybe I'll take the first part and then turn it over to Matt for the partnering piece. I think it's premature for us to talk about the logistics and how easy it will be to recruit or not. Because as you heard, we haven't yet defined the design. The duration is 1 element. The duration often depends on the sample size as well, the level of control, how are we using it? Are we leveraging also external control using patient statistics or other types of techniques. So it's really premature to do that. Having said that, I think we are very comfortable with the interest of patients. We've seen that after we've published the results back at September, and that has also increased through this a lot of the great work that's been done over the past number of months, but our externally facing group in dealing with these various sites across the U.S. predominantly. And I'm not really too worried right now, but we cannot give you more details until we figure that out a bit more of the design.

Yes. On the partnering side, I also think it's a little too early. We need to understand what the Phase III study design and protocol is going to be the number of years and the investment that's required. I mean, we're obviously focused right now. We've got a strong balance sheet, and our strategy has been to take this forward and commercialize it ourselves. We really believe in this product it deserves to be taken forward. It needs to be brought to patients, and we're going to do everything we possibly can to do that. And if partnering plays a role in it, then we'll have to evaluate it at that time, but it's a little premature to weigh in on that right now.

Your next question comes from the line of Ali Merrill with Barclays.

This is Jason on for Elli. So first, can you give some more color on the different scenarios for a potential Phase III design. So what are you going to the FDA within proposing? And has the FDA so far given any guidance on the length of the study or endpoints? And then secondly, across these different scenarios, what would the cost of the Huntington Phase III program look like? And does your cash runway include this?

Thanks, Jasmine. It's really premature to be able to get into those details. I -- whatever I say now would definitely be different after we talk -- so there's been no specific discussions on the length of the trial. As we said, the FDA was very clear about their strong recommendation to do a double-blind sham-controlled trial, that is -- that is adequately powered, which is, again, the right thing to do to be able to evaluate this as the adequately powered part. Now we need to discuss with them whether there is openness to use maybe other designs or how we can leverage the external control. But honestly, whatever I say now, really is not -- it's very high likely to change. So I really would not like to go down that path. And what's the other question? For Christian, regarding the run rate.

Yes. So I mean, same comment a bit as Vale with all the uncertainties around the investments into kind of the various late-stage opportunities we have kind of run scenario analysis with built in development spend, but it's way too early to comment on specifically how much of that would relate to 130 vis-a-vis 260 or 191 .

Your next question comes from the line of Susan Zane with Kempen.

This is Suzanne from Kempen. Maybe 1 clarifying question on the indices program about other jurisdictions. What regions are you talking about? And what's the status of your discussions with regulators outside of the U.S.? And then I have 1 for the program. Did I catch correctly that the update in Q2 will be on 6 patients from the first dose cohort with 6 months follow-up? Or will there also be some early data from the second dose cohort -- and perhaps for seizure specifically, can you give a sense of what reduction in the seizure frequency we should consider as good or what level would be a great result.

Absolutely. So on the first question around ex U.S., I think we're looking at a number of different jurisdictions at the moment. We're taking into consideration a number of factors. We're looking at obviously epidemiology regulatory pathways and then also pricing and reimbursement, looking, as I mentioned, at named patient programs and early access programs that are applicable to rare diseases and really taking that into assessment as we think about the strategy moving forward for ex U.S. regions. We've obviously mentioned that we're going to be in discussions with both MHRA in the U.K. and EMA from a European perspective. And then we're going to be looking at what other opportunities that affords us outside of those 2 jurisdictions. So that's on the first question and then handing over to Walid on the epilepsy question.

Yes. So on the epilepsy, we will be presenting the data on exactly what you said, the first 6 patients, 6-month seizure frequency. Honestly, this is a Phase I study. So we have not yet set an expectation. We're trying to figure out overall safety, tolerability and evidence of pharmacodynamic effect. It's a learning process. So more to come once we share the data.

Your next question comes from the line of Luca Issi with RBC Capital Markets.

Maybe if I can circle back on the ex U.S. opportunity here Matt and Kyle. How should I think about the overall commercial opportunity here? I believe Roche was able to generate close to $100 million a quarter from selling the levies to ex U.S. before the drug obviously run into safety issues. Is that the right comp for us to think about it? Or would you advise against us? .

Absolutely. So I think it's probably a little bit premature to be talking about commercial opportunity because we're truly in the planning and strategy phase around thinking through what opportunities would we be going after. But I do think that what we're bringing into the thinking is exactly that Roche comp around how have they gone after certain regions through named patient and early access programs as well as other cell and gene therapies that have walked this path ahead of us, and we will be taking those learnings on board. So a bit premature on commercial opportunity, but I do think that we will be looking at Roche and other companies for thinking through best practices.

Your next question comes from the line of Salveen Richter with Goldman Sachs.

Can you just help us understand the totality of the sticking points with the FDA here? And why a sham controlled is required versus a prospective natural history comparator?

Thanks, Salveen. Yes, the FDA at the pre-BLA meeting raised the point that those studies were designed as hypothesis-generating studies and any such analysis after we've collected the data and we looked at them would be considered post hoc. And then recently, they reverted to start looking at the double-blind part of the U.S. study and raising questions around absence of any clinical or biomarker signal in that smaller U.S. study, which was sham-controlled. As I said in my comments earlier, we really do not have the same interpretation as the FDA in this type of rare disease where there's slow progression, and we are taking people early in their disease. It's really difficult to detect a meaningful and reliable change after 1 year in a Phase I/II study such as ours.

And as such, you need to start looking at data from a subsequent time point. And what we have seen with AMT-130 that every time we looked at the data, the signal became more and more evident and as such, we believe that this warrants an evaluation compared to an external control, which is the kind of regulatory flexibility that 1 should be affording to diseases such as Huntington, which are monogenetic, progressive and rare. And the also procedure that we do, which is one-time administered gene therapy. So these are the kind of things that we're going to be discussing with the FDA and continue that dialogue because fundamentally, the AMT-130 is doing what we have been expecting it to do, and that effect continues to be stronger and stronger.

And we're going to keep on analyzing these data and accumulating more data. And we're hopeful that we're going to be able to align with the FDA on a study design that would allow us to confirm these findings and then we will take this 1 step at a time as we start getting more clarity with them.

Your next question comes from the line of Uy Ear at Mizuho.

I guess I'm just still don't quite understand why the FDA is requiring a sham study. Like I understand the objection the FDA had previously and it didn't sound that in your Phase I/II study, it didn't sound it like the FDA was objecting to natural history. I guess this time around, what is it about the -- Is there anything about the natural history database that they objected to or the kind of data or the kind of statistical plan that we involved with using natural history that they're not comfortable with. I guess that's the first question. And the second question is, Matt, are you committed to taking this forward even with a sham study?

Yes. I mean, Walid can chime in. But I mean we disclosed that back in November of 2024, that the FDA had stated in writing that we may use the data from the Phase I/II study in comparison to an external control as the primary basis for a BLA submission. And honestly, I'm looking at Walid here, I don't think that they've necessarily had any criticisms of the Enroll HD database. I mean this is a database, again, with more than 30,000 participants. It's been collected over the last 14 years, and it's a clinical-grade natural history. I mean, this is almost -- I mean this is effectively a clinical trial. So -- and moreover, part of the comparison was actually contemporaneous with the patients that we enrolled.

So there's a lot of check boxes there. And it's puzzling to us other than the fact that a sham-controlled study is certainly gold standard science. But -- it's hard to understand why with such a plethora and treasure trove of natural history that not being able to leverage that in a way for a registrational pathway would obviously would be very disappointing.

With respect to your second question, I mean, I believe in my soul that AMT-130 can benefit patients with HD. And over the years, I've gotten to know these patients, know their families and I understand the urgency of this unmet need. And if there is a study that we believe is feasible and ethical, we're going to do everything we can to drive AMT-130 forward.

Your next question comes from the line of Patrick Trucchio with H.C. Wainwright.

This is Louis Santos and Patrick. I just wanted to ask if there was anything in the FDA's feedback that's precluded potential accelerated path with this supposed Phase III study based on an interim analysis, say, of surrogates, including NFL.

Yes, there was no discussion on this with the FDA, but there's no reason to think that. Actually, it was verbally communicated in the previous time that, that would be possible as well. So I do think that, that could be an option if we go down that path. But again, let's first discuss what that phase season would look like, and then what potential accelerated approval or full approval pathway that would be.

Your next question comes from the line of Kristen Kluska with Cantor.

Was part of your discussions with the FDA around a lack of biomarker data? And is there going to be an expectation that you'll be able to show some of this in a sham-controlled study. .

So the FDA, as I said, reverted back to looking at the 12-month data of our U.S. study because that's the only study that had the sham control in it and they raised challenges they don't see biomarker data in that small sample size over 1 year. There was no specific discussion on 3-year data or requirement for what we need to show or not at this point. So it's really premature for me to get into that. But we will provide more details on the Phase III and the FDA expectations after we align with them in the second quarter.

Your next question comes from the line of Yanan Zhu with Wells Fargo.

This is Juan on for Jan. So in previous questions, you mentioned that you were trying to avoid Phase III design that will be too difficult or too challenging to the patients. Can you elaborate on that point? Are you talking about the length of study? And what would be considered too difficult? Is it like a 3-year or longer study? And I have a quick follow-up. .

Yes. I think the concept of having a sham surgery where patients would be essentially anesthetized for an extended period of time 10 to 12 hours where you have to cut through the skin and maybe superficially drill a hole in the skull without really going through the bone. All of these elements represent risk for these patients, especially if the length of the study is 2 or 3 years, and they're going to be spending all this time not knowing that whether they get a drug or not. And then potentially at the end of this period, they might have progressed enough that they cannot benefit from the drug or they will never really get back that level of worsening. I think this is where we find it a bit difficult, particularly with the type of therapy that we provide. And so that's why we're very keen to work with the FDA.

I mean we know that ultimately, we have the same goal. We want to bring safe and effective medicine to patients. We share that. And we know that the FDA definitely cares about patients. They indicated that. We just want to work with them and appeal to their flexibility to be able to design, again, scientifically sound studies to leverage the available data that exists now so that we can minimize the burden to the patient as much as possible.

Got it. And in plan Type B meeting. Is there any additional evidence that you plan to present to FDA or is just a discussion on the Phase III design?

No, it will be only to discuss the Phase III design. We're not doing any additional analyses or anything like that until we update the SAP and the next time we share the data would be in the fourth quarter. .

Your next question comes from the line of Rod Lee with Wolfe search.

Just another quick follow-up to the trial design. So what is the biggest pushback from the FDA? Why do they feel strongly that you need to run the Sham control trial because they seem to be open to a single-arm trial like for stoke therapeutics and practices? Just wondering what are the key differences here?

Well, you're absolutely right. They're certainly precedent for genetic diseases and one-time administrative medicines to be approvable without doing a placebo-controlled study. I mean, it's a theoretical benefit, right? I mean there's a reason why sham controlled or placebo-controlled is gold standard, and that's because it addresses potential bias, whether that's a selection bias or motivational bias. There's no disagreement that a placebo-controlled study is a higher level of robustness. But in our view, it really doesn't reflect regulatory flexibility given the urgency of unmet need here nor does it necessarily take under consideration the tremendous amount of natural history data that can be leveraged in order to provide a very useful and meaningful comparator. So -- but that's what -- based on our understanding, what we think the FDA is seeking is a maximum reduction of potential bias in recommending that we do a sham-controlled study.

Right. Just to be clear, if they really want a SAM controlled trial was still dedicated to move forward to a trial.

Yes. I mean I think we're going to do some feasibility work. I mean we did do a sham controlled portion of our Phase I/II study. It was a 1-year in a much smaller study. But I think if we do our feasibility work, and we think it's feasible and the patient community is supportive of it, I think we're seriously going to consider that. I think we need to. We have to. If this is feasible and the patient community supported, we have a moral obligation given the strength of our data to continue to pursue this. I really feel that very strongly. And again, I understand these things cost money and they take time and that's something we can explore the best way to do that. But I'm here at this company because I want to bring therapies like AMT-130 to patient populations like Huntington's disease patients. .

And again, given the strength of our data, I think this is an endeavor that we continue to be dedicated to.

Ladies and gentlemen, that concludes today's call. Thank you for joining. Have a great day. You may now disconnect.

Good morning, and welcome to uniQure's Third Quarter 2025 Earnings Call. [Operator Instructions] As a reminder, this conference call is being recorded. I would now like to turn the call over to Chiara Russo, Senior Director of Investor Relations. Thank you. Please go ahead.

Good morning, and thank you for joining us for uniQure's Third Quarter of 2025 Earnings Call. Earlier this morning, uniQure released its financial results for the third quarter of 2025, and our press release is available on the Investors and Media section of our website at uniqure.com. Our 10-Q was also filed with the SEC earlier today. Joining me on the call this morning are Matt Kapusta, Chief Executive Officer; Dr. Walid Abi-Saab, Chief Medical Officer; Kylie O'Keefe, Chief Customer and Strategy Officer; and Christian Klemt, Chief Financial Officer. After our formal remarks, we'll open the call up for Q&A.

Before we begin, 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 information available to management only as of the date of this conference call. 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 most recent SEC 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 if new information becomes available in the future. Now let me introduce Matt Kapusta, uniQure's CEO.

Thanks, Chiara, and good morning, everyone. Thank you for joining today's third quarter conference call. As you know, in the third quarter, we announced positive top line data from our pivotal Phase I/II study of AMT-130 in Huntington's disease, the first gene therapy to demonstrate statistically significant slowing of disease progression in Huntington's disease. These groundbreaking results represent an important milestone not only for uniQure, but also for patients and families who have long awaited a potential disease-modifying therapy.

As previously disclosed, we met with the FDA in late October to review our data and discuss the potential submission of a BLA for AMT-130. Based on discussions at the meeting, we believe the FDA currently no longer agrees that the data from the Phase I/II studies of AMT-130 in comparison to an external control may be adequate to provide primary evidence in support of a BLA submission. Consequently, the timing of a BLA submission for AMT-130 is now uncertain. This feedback represents a notable shift from prior communications with the FDA during multiple Type B meetings over the past year. We plan to urgently engage with the FDA to discuss next steps, and we expect to receive the formal meeting minutes within the next 30 days.

While the latest FDA feedback is certainly surprising and disappointing, we continue to strongly believe that AMT-130 has the potential to provide significant benefit to patients. We believe the data presented to date, widely recognized as the most compelling ever generated in Huntington's disease, provides substantial evidence of therapeutic effect. Every year, thousands of Americans die because of Huntington's disease and thousands more are newly diagnosed. We believe AMT-130 has the potential to significantly slow disease progression and exemplifies the type of transformative innovation in rare diseases the FDA has pledged to support.

We remain fully committed to our partners, investigators and most importantly, to Huntington's patients and their families and to working collaboratively with the FDA to bring this therapy to Huntington's patients in the U.S. as rapidly as possible. We will continue to act with urgency, transparency and discipline as we work to deliver on the promise of gene therapy to transform lives. I will now turn the call over to Walid.

Thank you, Matt. Good morning and good afternoon, everyone. I would like to start by reiterating that the recent feedback from discussions at our pre-BLA meeting does not change our belief in the data. We continue to believe that AMT-130 represents the most compelling therapeutic data set generated in Huntington's disease to date. The true highlight of the third quarter was the positive top line data from our pivotal Phase I/II study of AMT-130 in Huntington's disease. Before I go on, I want to thank our employees, investigators, partners and especially the patients and families who have been participating in the CHDI natural history studies and our clinical studies. It's thanks to their deep commitment and efforts that we have been able to achieve such progress.

In September, we reported top line data with the high dose of AMT-130 demonstrated a statistically significant 75% slowing of disease progression as measured by the composite Unified Huntington's Disease Rating Scale (cUHDRS) at the 3 years compared to a propensity score matched external control derived from the Enroll-HD natural data set, meeting the pivotal study prespecified primary endpoint. Equally important, patients treated with high-dose AMT-130 demonstrated a statistically significant 60% slowing of disease progression at 3 years as measured by the total functional capacity, a key secondary endpoint.

Moreover, Cerebrospinal fluid, neurofilament light chain, a well-characterized and supportive biomarker measuring neurodegeneration was below baseline at 36 months in patients treated with high-dose AMT-130. The top line data from the high dose were supported by consistent results in multiple sensitivity analyses demonstrating the robustness of these findings. We believe these results provide the first clinical evidence that gene therapy can potentially alter the course of Huntington's disease. In keeping with the spirit of full transparency for the scientific and medical communities, we are working diligently on a comprehensive publication strategy, starting with publishing our full data results in a well-respected peer-reviewed medical journal.

As Matt noted earlier, we met with the FDA for a pre-BLA meeting in October. And based on discussions of the meeting, we believe that the FDA currently no longer agrees that data from the Phase I/II studies of AMT-130 in comparison to an external control may be adequate to provide primary evidence in support of a BLA submission. This feedback was unexpected. We believe AMT-130 has the potential to significantly slow disease progression. We plan to urgently interact with the FDA and are fully committed to working with the agency to find an expeditious path forward.

Turning now to AMT-260 for mesial temporal lobe epilepsy. In May, we announced initial data from the first treated patients with 5 months of follow-up. At that time, we observed promising reduction in seizure frequency over the first 5 months of follow-up with no serious adverse events. This data generated enthusiasm among investigators and potential patients. We have now activated 17 recruiting sites in the United States and completed enrollment of the first 3 patients in the first cohort. Following a favorable review by the independent data monitoring committee, recruitment has now expanded into mesial temporal lobe epilepsy in the dominant hemisphere and the initiation of a second cohort at a higher dose for the protocol. We expect to provide updated data from the study in the first half of 2026.

Moving to Fabry disease. In September, we also reported encouraging results from the ongoing Phase I/IIa trial of AMT-191, which were presented at the International Congress of Inborn Errors of Metabolism in Kyoto. Across the 4 patients treated in the first cohort, we observed supraphysiological alpha-Gal A enzyme activity with all patients successfully withdrawn from enzyme replacement therapy while maintaining stable plasma lyso-Gb3 levels through the July 24, 2025 data cutoff date. These results, together with a manageable safety and tolerability profile, reinforce the potential of AMT-191 to be a one-time dose gene therapy for Fabry disease. Enrollment in the second lower dose cohort has been completed with a third cohort currently enrolling. We expect to share updated data in the first half of 2026.

I will now touch on some additional pipeline updates. We have voluntarily paused enrollment in the Phase I/II EPISOD1 trial of AMT-162 for SOD1 ALS based on the recommendation of the independent data monitoring committee following a September 2025 review of the preliminary data related to the safety and efficacy of AMT-162 in the context of a dose-limiting toxicity that was observed in 1 patient in the second cohort. This event resulted in a serious adverse event determined to be related to AMT-162. At this time, we will continue to collect and evaluate data from the patients treated with AMT-162. To summarize, the third quarter marked a milestone for AMT-130 with a positive top line data from our pivotal Phase I/II studies. The recent feedback from the FDA has introduced uncertainty into the path forward, but we believe in our data, and we are focused on working with the agency to define the next steps.

Now I will turn the call over to Kylie to discuss our recent patient advocacy work. Kylie?

Thank you, Walid. As both Matt and Walid have said, our commitment to the HD community remains unwavering. Following our September data announcement, we experienced a groundswell of hope and support from patients, patient advocacy groups, clinicians and scientists alike. We understand and deeply appreciate the concern and disappointment expressed by the community following our announcement last week regarding the pre-BLA meeting with the FDA. We are reminded, however, that every step of this journey, including moments like this reflect the seriousness of our mission and the importance of getting this right for HD patients.

During this period, our commercial and medical teams continue to thoughtfully plan and execute with discipline and focus. Our primary focus continues to be on stakeholder engagement and education, including treatment centers of excellence, payers and patient advocacy to best position us to be fully prepared for a strong and informed potential launch of AMT-130. Concurrently, as we have a focus on building the foundational strategy for the U.S. market for a potential launch of AMT-130, we are also looking to additional potential markets outside of the U.S., such as the EU and the U.K.

The feedback we are receiving from the physician and patient community reinforces both the high level of unmet need and the enthusiasm for the potential of AMT-130. Their support continues to motivate our team, and we remain committed to maintaining open communication and collaborating with the community as we plan next steps. We believe deeply in our science, the data we have generated to date and the impact that this therapy could have for HD patients. Now I will turn the call over to Christian for a financial update. Christian?

Thank you, Kylie. I'll now be sharing financial highlights of the third quarter of 2025. Please refer to the earnings press release issued this morning and our quarterly filing with the SEC for additional detail. Revenue for the 3 months ended September 30, 2025, was $3.7 million compared to $2.3 million in the same period in 2024. The increase of $1.4 million in revenue resulted from a $1.5 million increase in license revenues and a decrease of $0.1 million from collaboration revenues. Cost of contract manufacturing revenues were 0 for the 3 months ended September 30, 2025, compared to $0.8 million for the same period in 2024.

Following the divestment of the Lexington facility in July 2024, cost of contract manufacturing revenues are recorded net of revenue within other expenses. Research and development expenses were $34.4 million for the 3 months ended September 30, 2025, compared to $30.6 million during the same period in 2024. The $3.8 million increase was driven by an increase of $10.1 million in direct research and development expenses, of which $6.6 million related to preparation for the BLA submission of AMT-130, offset by a decrease of $3.4 million in severance costs and a $3 million decrease in costs related to disposables, facilities and other expenses.

Selling, general and administrative expenses were $19.4 million for the 3 months ended September 30, 2025, compared to $11.6 million during the same period in 2024. The $7.8 million increase was primarily related to a $2.4 million increase in employee-related expenses and a $4.9 million increase in professional fees, including $3 million incurred to support the preparation of potential commercialization of AMT-130 in the United States. Cash, cash equivalents and investment securities totaled $649.2 million (sic) [ $694.2 million ] as of September 30, 2025, compared to $376.5 million (sic) [ $367.5 million ] as of December 31, 2024. The increase is primarily related to the net proceeds of $404.2 million from our public offerings this year.

With this strong balance sheet, we believe uniQure is well positioned to execute its clinical and operational priorities. We expect cash, cash equivalents and investment securities will be sufficient to fund operations into 2029. I'll now turn the call back over to Matt.

Thank you, Christian. As you've heard today, the third quarter of 2025 was a pivotal one for uniQure, and we continue to have strong conviction in both the compelling data set and therapeutic potential for AMT-130. Our focus now is on working with the FDA to clarify next steps and determine the most expeditious path to bring AMT-130 to patients in the U.S. In parallel, we will plan to advance discussions with other regulatory agencies, including those in the European Union and the United Kingdom. As we move forward, we do so with confidence in our science, clarity in our mission and a deep determination to make a meaningful difference for patients and families affected by Huntington's disease.

Before we open up for questions, I'd like to note that because we have not yet received the final meeting minutes from our pre-BLA meeting with the FDA and out of respect for the agency and our shared goal of advancing AMT-130 for patients with Huntington's disease, we will strictly limit our responses about that meeting to the information disclosed in our November 3, 2025 press release. We appreciate your understanding and are happy to address other questions you may have. Operator, please go ahead and open the call.

[Operator Instructions] Our first question today comes from Joe Schwartz from Leerink Partners.

Great. So the treatment effect you've reported out to 3 years is quite large. So I'm wondering, to what extent have you stress tested the results in order to see what a very conservative rendition of the results would look like? For example, could you remind us how you constructed the external control arm to consider whether there were any potential sources of bias?

Thanks, Joe. Walid, do you want to answer that one?

Can you hear me?

Yes.

You can. I'm sorry, I wasn't sure if I'm muted or not.

Yes, we can.

Yes. Thank you. All right. Thanks for the question. So actually, what we have done is essentially follow a rigorous way to do the propensity score-matching with Enroll-HD. I think Enroll-HD lends itself to provide a fairly robust data because of the size of it, you get very good matches. And what we have done in discussion with the FDA prepared a series of sensitivity testing evaluating propensity score-matching using different types of matching the propensity score-weighting. We've also looked at a smaller number of variables, which was part of an SAP that we have proposed much earlier in the process during the RMAT application.

We looked at regional differences. We looked at comorbidities based on medication and so on and so forth. And last but not least, we compared to TRACK and PREDICT a sensitivity analysis, again, as part of the pre-agreed types of sensitivity analysis with the agency. And across a variety of these analyses, the results were very consistent, demonstrating the robustness of these findings. And that's why we have really strong confidence in the results that we've seen.

But regardless, if you also look at the numerical change from baseline in our patient population and compare it to a number of data that's being published by a number of studies that are run in that space in comparable patients, you see that the magnitude of the change from baseline at 3 years is very small compared to one would expect in placebo or untreated subjects.

Our next question comes from Uy Ear from Mizuho.

Maybe just help us understand a little bit about what happened in AMT-162. Could you kind of remind us what -- whether this -- what the vector was and whether it was similar to the other pipeline studies? And along with that, what was the dose difference between the first cohort and the second cohort?

Yes. Thanks for the question. We haven't quite disclosed all of the data about the dose so far. But with this product, we have seen previously in a compassionate use that was the case of dorsal root ganglion toxicity. It's a known adverse event, particularly for this route of administration. And we knew and we were monitoring very carefully with this. Unfortunately, we've seen that at the middle dose, which I can tell you is about threefold higher than the low dose. And as a result, we backed down. But now we're monitoring the data to see over time how this will evolve, and we will have a discussion with the experts and the IDMC to determine the next steps for this program. We should be able to come back in the first half of next year with some answers on this.

And just to be clear, Uy Ear, this is a totally different capsid than what we use in our other programs and a different mode of administration.

Our next question comes from Salveen Richter from Goldman Sachs.

This is Lydia on for Salveen. Could you just talk to what details you hope to learn from the final meeting minutes here in the next 30 days?

Yes. I think what I would say is we don't want to speculate on what will be in the minutes. We assume that they'll reflect mostly the conversation that we had in Washington, D.C. But most importantly, we hope it will give a sense of the concerns that the FDA has and give us an outline for how to address those concerns in a subsequent meeting with the FDA.

Our next question comes from Joseph Thome from TD Cowen.

I guess, are you able to kind of confirm that prior meeting minute documents did confirm the ability to file for accelerated approval based on the cUHDRS, maybe like the meeting minutes from the RMAT meeting at the end of 2024. Was that officially documented in what they sent to you? And maybe how much detail do they go into in these meeting minute documents around the definition of the statistical analysis plan and the external comparator?

Yes. Joe, I can confirm that in our November 2024 multidisciplinary meeting with the FDA and the written comments that we received, the FDA stated that the data from the Phase I/II study in comparison to an external control may serve as the primary basis of a BLA submission. They also confirmed that the composite UHDRS would be considered an acceptable intermediate clinical endpoint to support accelerated approval. In that particular meeting, they didn't get into specifics on the statistical analysis plan, but had recommended that we prespecified stats plan, and that was discussed in detail as well as the natural history protocol in our April 2025 meeting with the FDA.

Our next question comes from Luca Issi from RBC Capital Markets.

Maybe, Matt, again, I appreciate the situation is still fluid here, but can you just talk about what needs to happen from here over the next few weeks in order for you to continue to invest capital in Huntington? I guess what I'm trying to ask here is, where do you draw the line between continuing to fight this versus just give up? Like any color there much appreciated.

Yes, I wouldn't characterize this as a fight. I think that we are 100% committed to continuing to collaborate and partner with the FDA to determine an expedited path to submit a BLA. I think we strongly believe that AMT-130 can meaningfully benefit patients. I think we feel that we have what is considered to be the most compelling data set in the field of Huntington's with 3 years of clinical outcomes data showing a meaningful slowing of disease progression. And we think that if there are concerns or issues that they ought to be addressed in a proper review.

And so we will continue to work with the FDA to address any concerns they have with the hope of having an expeditious submission of a BLA in the near future. That is the pathway that we're going to be focused on. And we are committed -- we believe we have a drug that works. We have a patient group that is -- that has an urgent need, and we're committed to doing everything we can to bring this to them as quickly as possible.

Our next question comes from Yanan Zhu from Wells Fargo.

Just first, a quick clarification for the ALS program, is it intrathecal delivery? And if so, is the AE, the dorsal root ganglion AE previously known to this route? Then maybe just on the Huntington's program, just wondering, can you characterize how motivated or mobilized the patient and doctor community is on this issue and how that could help move the issue around?

Okay. Walid, do you want to answer the first one, and then I'll kick it to Kylie to do the second.

Thanks, Matt. Yes. On the first question, the answer is yes to both. So intrathecal delivery, and it's dorsal root ganglion toxicity, which, again, as I said, unfortunately, is associated with this mode of administration, and we knew this was a risk. So yes. Over to you, Kylie.

Thanks, Walid. Yes, as I just said, the patient and physician community are very motivated. They have a huge unmet medical need and are collaboratively working together to look at how to move this forward. I think one of the things that's important is we received a big expression of hope and excitement coming out of the data and then to have this disappointment a few weeks later is a bit of an emotional roller coaster for the community. But I think they're working together to look forward and say, "How do we bring this therapy to patients."

Our next question comes from Patrick Trucchio from H.C. Wainwright.

This is [ Erabella ] on for Patrick. I was just wondering if you could clarify if you've received any EMA or MHRA preliminary feedback on accepting the same data set and external control for AMT-130 as primary evidence? And could you see ex U.S. submissions proceeding ahead of FDA approval?

Walid, do you want to answer that?

Sure. So we have not yet engaged in the U.K. or EMA -- MHRA or EMA. That is the plan to go next. We're prioritizing the FDA. But I will say that we are committed to work with the FDA also to continue to find a path forward and also with other regulatory agencies. And we will advance as quickly as possible on all these fronts to bring this therapy to patients as quickly as possible.

[Operator Instructions] Our next question comes from Paul Matteis from Stifel.

As it relates to the meeting, again, answer whatever you're comfortable with. But given that your dialogue here, I guess, as I understand it, has been with a relatively similar group of people across the spring meeting and then last -- November last year, when they came out and told you that they didn't think this path was no longer supportive of a BLA, did you ask them why and what exactly had changed? And then just separately, can you clarify for us what specific data have you shared with the FDA at this point? And have they seen more data from this 3-year analysis than we have?

Yes, Paul, unfortunately, we're not going to be able to comment on the details of the specific meeting. But we do hope for clarity once we do receive minutes. And to the extent that there are material updates, we will endeavor to update investors and analysts. So I think that's the answer to your first question. And then the second question. Okay. Yes. On the data -- no, the data that was submitted to the FDA was consistent with the data that we've shared publicly a number of weeks ago. Obviously, there's some additional data like sensitivity analyses that haven't been presented, but there was no new follow-up or additional data that was provided to the agency.

We have no further questions. This will conclude today's question-and-answer session and today's call. You may now disconnect.