uniQure N.V. (QURE) Q2 2026 Earnings Report, Transcript and Summary

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 $0.6 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.

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.

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.

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?

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?

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?

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?

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. 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?

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.