QURE

Hello, thank you for standing by. My name is Joy, I will be your conference operator today. At this time, I would like to welcome everyone to the uniQure Second Quarter 2026 Earnings Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number 1 on your telephone keypad. If you would like to withdraw your question, press star 1 again. We kindly ask that you please limit your questions to one and one follow-up. Thank you. I would now like to turn the call over to Chiara Russo, Senior Director of Investor Relations. Please go ahead, ma'am.

Good morning, thank you for joining us for uniQure's second quarter of 2026 earnings call. Earlier this morning, uniQure released financial results second quarter of 2026, 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, Christian Klemt, our Chief Financial Officer. After our formal remarks, we'll open up the call for Q&A. Before we begin, please know 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, 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, 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 on near-term regulatory pathways for AMT-130, announced promising early data from our Fabry disease and refractory temporal lobe epilepsy programs, 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, Christian on the financials. I will 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 three-year data is reasonable. This alignment was later confirmed in the final meeting minutes we recently received. 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 timeframe 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. We are working collaboratively with them on a confirmatory study design. We are on track to submit the BLA this quarter. Walid will provide additional details later in the call. In parallel, after a successful pre-submission 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 four-year AMT-130 data analyses from the Phase I/II studies. We look forward to presenting the four-year data results in September. Beyond AMT-130, we are encouraged by the progress across our broader pipeline.

Early data from our Phase I/II-A 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. 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. 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. 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 and 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 three-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. 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 timeline. 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. 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 30th cutoff date for the four-year data, keeping us on schedule for the expected September update.

We currently plan to disclose safety and tolerability data through four years of follow-up. The update will also include top-line data from 12 high and 12 low-dose patients at four years, with an additional three patients at the high dose for a total of 15 patients now with three 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 four-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 four 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 29th, 2026, data cut off, three of six patients in the first low-dose cohort achieved meaningful reductions in disabling seizures during months four through six, ranging from 79%-100% below baseline. The remaining three patients showed variable outcomes over the same period, ranging from a 33% decrease to a 36% increase from baseline. 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 two 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 a March 15, 2026, cutoff date. Patient follow-up ranged from three 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 three 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 two 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 a course of immunosuppression.

Now I will turn the call over to Kylie to discuss our ongoing effort 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 three-year phase I/II data will be acceptable as the primary basis for a BLA submission represents the regulatory clarity our commercial team has been preparing for. With a BLA submission planned for the third quarter, an MAA submission to the U.K. MHRA on the same timeline, our commercial preparations have taken on renewed focus and urgency across three 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 and 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 three 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 increase in license revenue compared to the prior period. Research and development expenses were $34 million for the three 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 $500,000 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 three months ended June 30, 2026, compared to $13.5 million during the same period in 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 $700,000 increase in intellectual property fees and a $700,000 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 equivalents, and investment securities will be sufficient to fund operations into 2030. I 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 four-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 30th data cutoff passed, we are in a quiet period on the AMT-130 four-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.

We will now begin the question and answer session. If you are dialed in and would like to ask a question, simply press star then the number one on your telephone keypad to raise your hand and enter the queue. We kindly ask that you please limit your questions to one and one follow-up. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Debjit Chattopadhyay with Guggenheim Securities.

Hey, good morning, thank you for taking my questions. Given the strength of the three-year data, what would you consider to be the best outcome for the four-year data? What role do you think the four-year data are going to play in any potential AdCom that one should expect for a first-in-class therapy for Huntington's?

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

Got it. Just one more follow-up here. Given that the complementary study needs to be nearly fully enrolled at the time of any Accelerated Approval, how quickly can the team operationalize this? Any clarity on the number of patients you're likely to enroll in the study would be helpful. Thank you so much, and good luck going forward.

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

Yeah, we got you.

Do you want me to answer this?

Yeah, please go ahead, Walid.

All right. Essentially, it's our belief that the fundamental intent of the FDA is that for all confirmatory studies, is to ensure that they are completed in a timely manner after approval. We are confident we can demonstrate that. You talked about sample size. We haven't yet finalized this with the FDA. It's kind of premature for us to do this. 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. 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. We believe that the way we are taking this approach with a global trial gives us a credible path to get there. Not sure if there were a couple of other little things that you asked, Debjit. 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. Thanks, Debjit.

All right, thank you.

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

Thanks. 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 one throughput per activated center?

Yeah, thanks, Joe. Kylie, you want to answer that one?

Yeah, 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. This has been incredibly important, as you said, to get them to understand these institutional nuances that occur across the different hospitals. One of the things that we have learned is that no hospital is the same. 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. 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.

Hi, this is Matthew for Paul. Thank you so much for taking our question and 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? 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? Thank you so much.

Thanks, Matthew.

As I mentioned

Go ahead, Walid.

Sorry, Matt. 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. This is moving forward, we will be updating you as the data mature. In terms of the shorter surgical, 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. Thanks.

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

Hi, team. This is Shelby on for Luca, and thanks for taking the question. Maybe on the regulatory setup for Huntington's. 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 three-year data agreed upon as the primary basis for the BLA? Any color there, much appreciated. Thanks.

Yeah, thanks for the question. Obviously, we're aware of the AdComs going on this week, and appreciate that those are serious diseases. It's not appropriate for us to comment on those particular AdComs. 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. 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.

Hi, good morning. This is Lydia on for Salveen. Thanks so much for taking our question. 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. Thanks so much

Hey, Walid, do you want to answer that one?

Sure. Thanks, Matt. Yeah, I think, the study design is straightforward. 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 ask in terms of retention. We believe that in our case, there's going to be a couple of items that we're 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 after three 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 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. We will be using statistical techniques and in agreement with the agency about how we will deal with those dropouts. Overall, we do feel very confident that we will be able to recruit the study and execute it in such a way that we can draw conclusions on it.

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 Elli Murrell with Barclays.

Hi, this is Jasmine on for Elli. Thank you for the question. Is your current expectation still that you will get priority review? 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? How long would you potentially expect enrollment in the confirmatory trial to take? Thank you.

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. 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. Given the unmet need here, we think that there's a reasonable chance that that would be accepted by the FDA. Ultimately, that's to the FDA's discretion. On to you, Walid.

Thanks, Matt. Regarding confidence and the study conduct, I think we prepared for this. We're working diligently within ClinOps to be able to do that. 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 implication about the sample size. Once we do that, we will be able to communicate, we will be able to give you a better idea about the timeline it will take us to recruit this trial.

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

Hi, guys. Congrats on all the progress, and thanks for taking our questions. I guess 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 application won't be approved or will be held until it's completed? The second question is, could you maybe just provide, walk us through the assumptions behind your 2030 cash runway? What does that include exactly? Thanks.

Yeah, thanks for the questions. I'll handle the first question and then pass it over to Christian for the second question. 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. 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. The FDA wants to ensure that the study can be completed in a timely manner. 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. We feel very confident that we'll be able to complete this study in a timely manner to address the FDA's priorities as it relates to confirmatory studies. With that, I will pass it on to Christian.

Thanks, Matt. Yeah. The guidance into 2030 includes a number of things. First and foremost, enrolling the confirmatory trial, funding the confirmatory trial into 2030, funding the 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.

Okay. Thank you.

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

Hi there. Good morning. Thank you for taking my question. Can you review with us maybe how the SAP for the three-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? Then maybe relatedly with the June 30th cutoff date and the September data presentation for the four-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? Thank you.

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

Yes.

Okay. Yeah. Walid, why don't you answer? I think the question was have there been any adjustments to the three-year SAP? The second part is questions around the four-year analysis.

Yep. Thanks. Yeah. The three-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. That has not changed. Actually, there should be no reason to change it after the fact. With regard to the four-year analysis, the timelines are generally similar to what we've done for last year. We're on track to be able to share the results with you in September of this year.

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

Just to get back to the history a little bit. We met with the FDA back in April of 2025, a month after we submitted the briefing book for the SAP. 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. We would not expect it. These are the data that form the basis of the analysis, and the FDA is aware of those data. In recent discussion with the FDA in the recent Type B meeting, we aligned with them that the data from the 3-year data cut supports the BLA filing. That is what we're moving forward with.

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

Hi, this is Jeff on for Yanan. Thanks for taking our questions. 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? Separately, I believe I heard that total functional capacity at three 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 three 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 to support full approval? Thanks.

I'll take maybe the first question, then Walid you can talk about the second question, understanding that we haven't completed the alignment around the confirmatory study. Nevertheless, on the first question, we confirmed 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. There was 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.

Thank you. In terms of the magnitude effect of TFC, indeed as you saw in our top line from the three-year data analysis last year, the TFC changes were 60%.

In the confirmatory trial, we will be using that information. It will be complemented with the updated four-year analysis, because if you recall, we have three more patients that would have reached the three years in that analysis. We will have a total of 15 patients instead of the 12 that we reported on last year. We will 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, 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.

Hi, good morning. 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.

Yeah, this is not a surprise to us at all. 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. Our sense is that in discussions that the FDA have 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.

In terms of an Accelerated Approval, the FDA is comfortable that the composite cUHDRS 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 & Co.

Hi, team. Thanks for taking my questions. Maybe assuming approval, looking at the commercial launch, it's a first of its kind, potentially. 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. Thank you.

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

Yeah, absolutely. Thank you very much for the question. I think some of the characteristics that are going to be key launch criteria is focused 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 three 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.

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. 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. Thank you. Maybe just a small follow-up. I know that Huntington's is 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? Thank you.

Yeah. 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 talk about truth-seeking

We try to run the experiments to answer questions. 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 a 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, that's going to be how we continue to make capital allocation decisions going forward.

Again, if you would like to ask a question, press star one on your telephone keypad. Your next question comes from the line of Patrick Trucchio with H.C. Wainwright.

Hi. Thank you so much for taking the question. This is Arabella on for Patrick. I was just wondering, should we expect a pre-specified interim analysis built into the confirmatory study? If that was positive, say, at two years, could that support conversion to full approval prior to the three-year primary? Then also, do you have any other outstanding CMC items to work on before you can submit the BLA?

Yeah, 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. On the CMC, we feel confident that we've completed the activities that are required for the BLA submission. Obviously, 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, regarding the pre-specified 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 it should be part of it, but we haven't yet finalized it, I really cannot discuss more. Hang tight. More to come once we have that clarified.

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

Thanks for taking my question. 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? Secondly, it sounds like we don't expect enrollment of the confirmatory study to be a key limiting factor to get approval. Just want to confirm. Thanks.

Sure. I didn't catch the last part of that. 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. I don't know how helpful that would be there. Then can you just repeat the second part of the question?

Yeah. The second part is really about, do you expect enrollment of the confirmatory study to be a key limiting factor to get approval?

Well, I'll repeat what I said before. Accelerated approvals are conditional approvals. I think the FDA considers that flexibility because of these critically high unmet needs for Huntington's disease and other indications. The confirmatory studies are important. As I said, their fundamental focus is ensuring that they can be completed in a timely manner. The reality is they have wide discretion to do that. 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. I think it'll be a factor, but I think we feel confident that we can get the FDA comfortable on those key elements.

Thanks, 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. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one again. Thank you. I would now like to turn the call over to Chiara Russo, Senior Director of Investor Relations. Please go ahead.

Good morning, 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 know 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, 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 acknowledged the agency's feedback and remain focused on engaging constructively to find a 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 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 U.K. 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 three-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/II-A 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 gal A 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 from AMT-260 in the second quarter, the four-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 a one-time administered therapy. Additionally, we plan to solicit feedback on our statistical analysis plan for the 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 a marketing authorization application for AMT-130 in the third quarter of this year, supported by our three-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 three-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 non-dominant and dominant hemisphere MTLE, and we plan to provide an update later in the second quarter on all six treated patients with at least six 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 8th of this year, the study cutoff date, all 11 patients across three dose cohorts demonstrated elevated alpha-galactosidase A enzyme activity that was dose-dependent and durable over the observed follow-up period, ranging from more than one year in the longest follow-up patient at the high dose to four 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 18th of this year, all 11 dosed patients have discontinued ERT. On safety, as previously reported, two 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 five 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-US 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 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 three 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 7,000-8,000 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 would not only enable access in the U.K. We believe it could also enable early access or name 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 discipline 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 anti-seizure 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 multi-system 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 for 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 three months ended March 31st, 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 three months ended March 31st, 2026, compared to $36.1 million to the same period, 2025.

The $6.9 million decrease was driven by a $2.6 million decrease in fair value of continued 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 Administrative Expenses were $20.1 million for the three months ended March 31, 2026, compared to $10.9 million during the same period, 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 record-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 projects through 2026.

We expect that cash and 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 2026, 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.

At this time, I'd like to remind everyone in order to ask a question, press star then the number one on your telephone keypad. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Moritz Reiterer with Guggenheim Securities. Please go ahead.

Hi, this is Moritz on for David. Thanks so much for taking our question. I have two. The first one is around AMT-260.

Could you just give a little bit more sort of an overview of what the expectations are for the upcoming dataset 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. 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? Thank you.

Thank you. 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, you know, particularly seizure frequencies as measured by a diary in addition to a number of other endpoints. 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 a reduction of seizure frequency. You know, we're targeting at this stage a maybe 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. I will withhold any interpretation on these data.

Thank you.

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

Hi, this is Emily on for Paul. We wanted to ask a little bit more about the U.K. market dynamics, maybe if you could share any color. 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? Thank you.

Absolutely. Thanks, Emily, for the question. Maybe starting with the second part of the question. The vast majority of the patients that we alluded to, the 7,000-8,000, are treated at specialized centers. There is a collection of those patients that are managed by the specialized centers around the U.K., 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. That's work that has already started and is ongoing and will continue through a potential MHRA approval to bring this product to market.

Great. Thank you so much.

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

Thanks. 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?

Okay. Do you wanna start with the first one, Kylie?

Yeah, absolutely. Just talking through ability to secure reimbursement in markets outside of the U.S., Joe, 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 in parallel 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 QALY and ICER considerations. 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. That will be taking reimbursement as a primary consideration into focus.

Thanks.

This is Walid. I'll take the second question. Thanks, Joe. 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 data.

Thank you.

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

Good morning. Thanks for taking my questions. 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? Separately, just frame expectations for the four-year data in the third quarter and what sensitivity analyses these might include. Thank you.

Thanks. In terms of design elements of a new study to evaluate clinical efficacy, we can't really go into details because it depends on these 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 one-time 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. That is truly our goal in the meeting.

Regarding the analysis of the four-year data, in broad terms, they're actually going to be generally similar to the three-year analysis, with the addition, of course, of one more year of follow-up, which will bring the total number of patients at four years to 12 at the high dose and 12 at the low dose. In addition, there will be three patients at the high dose who would have completed three years, so making 15 patients who have reached the three-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 expectation 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 gonna become much more evident when compared to well-matched external controls.

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

Hi. Thanks for taking our question. This is Quan on for Yanan. Also on Huntington's disease, you mentioned that in the Type meeting you'll talk about, design of the new study and data statistical plan. Can you talk about, will you also cover the potential of an alternative regulatory path? Is there still a possibility to file without starting a new study? Thank you.

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 analysis. We do not intend to have a specific discussion about a regulatory path to filing at this point.

Got it. Thank you.

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

Hi. This is Peyton on for Joe. Thanks for taking our questions. I guess I'm 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 changed, planned changes to the surgical procedure in a potential commercial product, specifically any changes in the length of the time of the procedure? Does anything need to be done to validate or approve the cannulas that is used? Thanks.

Thanks, Peyton. 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. There are a number of centers that have already treated AMT-130 patients. This is just a small handful of the number of centers that exist in the U.K. that have neurosurgical stereotactic capabilities. 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.

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. 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.

Great. Thanks.

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

Oh, great. Thanks so much for taking my questions. maybe Matt or Walid, you know, kind of bigger picture, can you just maybe compare and contrast the Type A meeting you had in January, the FDA, versus the pre-submission meeting you had with the MHRA in the U.K.? Again, 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 data with single arm data with, like, historical control? Is that because they have a better appreciation for the unmet medical need? What's driving that dichotomy there? I think any color there much appreciated. Thanks so much.

Luca, it's obviously hard to get into the mind's eye of, you know, each of the regulatory authorities. You know, we've been saying this now for, you know, for 6+ months that we strongly believe in the strength of our data. You know, we've achieved 75% slowing of disease with high statistical significance out to three 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. There's a tremendous unmet need here where there's no disease-modifying treatments for these patients. I think, you know, based on the discussion that we had with the U.K., I think they recognized these elements. Walid, do you wanna chime in?

Yeah, I just wanna 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. 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. You know, at one point, there were more openness and flexibility with us. More recently, it's been a bit more difficult.

Again, we continue to work with the FDA, and at the end of the day, the data that we're gonna be generating will help, hopefully, to get us to where we need to go.

Got it. Thanks so much, guys.

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

Can you elaborate a bit on the range of outcomes for what we could learn from the Type B meeting? Then a second question, do you plan to request another meeting with the FDA after the data to pursue accelerated approval again based on the data? Thanks.

Yeah. I think at this juncture, just with the Type B meeting scheduled, we won't speculate on the range of meetings and on the range of outcomes. Then, you know, based on the discussion that we have, we'll ascertain whether there's 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.

Understood. Thanks.

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

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? A small one on your cash runway guidance into H2 2029. Can you remind us what parts of your business plan are or are not included in that guidance? Thank you.

This is Walid. I'll start with regulatory strategy beyond the U.K. and the U.S. 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.

Absolutely. 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. We're looking at countries that have named patient access and early access programs well-established, which there's 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 six months for a rare disease products. France also has the ATU program or the AAP program, which it has now evolved into. There's a number of other countries, Italy, for example, that has named patient and early access.

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.

Yeah. Yeah. Quickly on the runway, it's kind of the same assumption as for a couple of cues that we complete the ongoing clinical trials for TLE, HD, and Fabry. To get into the second half of 2029 does not allow us to simultaneously take forward all the candidates in kind of the most expedited manner. There will need to be prioritization decisions if we wanna maintain the runway.

All right. Your next question comes from the line of Patrick Trucchio with H.C. Wainwright. Please go ahead.

Thanks. Good morning. 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, you know, steroid prophylaxis or other follow-up criteria are necessary to move forward. 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.

Thanks, Patrick. Great questions. The per protocol, anytime we see a grade 3 increase in the or grade 3 adverse event, that could be potentially a DLT. Per protocol, we stop dosing. There's been very close collaboration with the IDMC informing the FDA. The patients are followed very closely and treated with a steroid as well as steroid sparing therapies. One patient fully recovered. The other one is really within a very close statistically recovering. I'm very pleased with the process. Once that is done, we will submit these data to the FDA for their review and discuss resuming dosing at one of these two doses.

In the meantime, the study is ongoing, we continue to dose with our low dose of 2E13, and we continue to follow the patients. At the end of the day, this is a phase I/II trial, 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 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, you know, data to suggest that there might be autoimmune in nature. We don't see that yet.

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. Based on these, we will be then making a decision about next steps with this program in the, you know, next six to 12 months.

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

Hi, good morning, everyone. Thanks for taking the questions. On AMT-130, of the 7,000-8,000 patients diagnosed today, what percent or number of them do you think would be potentially eligible for therapy at launch? Based on your timelines 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? Thank you.

Hi, Kristen. 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. I think as we sort of understand the market in more detail, we'll be able to share more specifics, more to come on that.

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. Though 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. That also will depend on how many questions, how complicated they are to get answers to. We are, you know, 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 and as I mentioned.

Your next question comes from a line of Daniil Gataulin with Chardan. Please go ahead.

Yes. Hi, good morning, guys. Thank you for taking my question. Quick one, 1:30 in the U.K., what 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 the MHRA decision for their approval, and how many patients could that potentially add?

Great. Thank you very much for the question. On the first part, which is capacity in the U.S., I think, ex-U.S., 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. 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. Obviously we would need to move through the process with NICE and ultimately NHS England to secure a formal recommendation and manage access agreement to be able to open up a larger potential pool.

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. 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's a number of countries that do that open up main 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. That's just to give you an example of some of the markets that are unlocked through a potential MHRA approval.

Thank you. Again, if you would like to ask a question, press star one on your telephone keypad. Your next question comes from the line of Rudy Li with Wolfe Research. Please go ahead.

Thanks for taking my question. I think you mentioned that you're now 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? 'Cause I'm still confused why they would require a sham control phase III instead of a single arm pivotal trial. Thanks.

Yeah. I think, you know, what we know is that we have the guidance that we got from the FDA, right, previously, which is, you know, their recommendation that we conduct another study. You know, that's why obviously we wanna go into the FDA and have a discussion around those design elements. As I say, you know, this upcoming meeting is an interaction with the review team. You know, there are tactical and technical matters that we wanna get through, you know, that include not only what I just described, but also a review of the statistical analysis plan. We're gonna continue to follow these patients.

As I said, you know, 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, you know, 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. You know, on top of that, clinical grade quality longitudinal data.

You know, to the extent that single arm studies and external control comparisons are acceptable for intractable diseases with high unmet need, we think there's a strong rationale, particularly given the slow progressing nature of HD, the one-time administrative nature of AMT-130, and the surgical delivery of the product. I think that's what we would say in that regard.

Very helpful. Thanks.

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.