uniQure N.V. (QURE) May 19, 2026 Conference Transcript

Well, great. Thanks. Hello, everybody. Luca Isis, Senior Biotech Analyst here at RBC Capital Market. And today's our great privilege to have Unicure as part of the 2026 Global Healthcare Conference, representing the company we have Matt Capusta, Chief Executive Officer. Matt, thanks so much for joining us. How are you doing today? Doing great. Thanks for having us, Luca. Very, very great. We have a very long list of questions here, Matt, but maybe before we go into the specifics, it would be fantastic if you can start maybe a little bit high level, maybe give us a few of the highlights of what progress has the organization made over the last few months, and most importantly, what's ahead here for Unicure.

Yeah, so we're in the middle of May already, and it's been a busy year. We have had a Type A meeting with the FDA on our lead program in Huntington's disease and have a Type B meeting coming up later this quarter. We had additional data that we presented on our Fabry disease gene therapy that shows continued therapeutic benefit for those patients across multiple doses. We can get into that a little bit later. We have data coming up on our temporal lobe epilepsy program towards the end of this quarter, where we'll have six-month follow-up data on patients from the first dose cohort. So we continue to execute, keep our head down, and do everything we can to try to advance our programs in the best interest of the patients that we serve.

Maybe just jumping into Huntington, you know, the perception from the outside is that maybe Prasad and, you know, Macari were a little skeptical about your data set, given some of the limitations that we know about your data set. They're obviously no longer, you know, at the FDA. Have you had any interactions with the FDA after their departures, maybe in formal conversations, emails and whatnot? Do you feel that there is a shift in the way they're perceiving the data sets or too early to comment or any thoughts?

Yeah, I think we have not had any formal interaction with the FDA since our Type A meeting at the end of January. So, you know, it's very difficult for us to get into the mind's eye of the FDA. I do think that the, you know, the criticism, I think, that we received in the last couple of interactions was largely around the lack of pre-specification associated with the analysis that we've done, which, of course, was challenging for us given that we started the study in 2018 and we're on the frontier of medicine as it relates to Huntington's disease. It is very important that we look at the FDA as a partner. I mean, it is very important that we collaborate with the FDA and we partner with the FDA. And we're obviously very much looking forward to our next interaction with them. And, you know, we believe in our data. That's probably the most important thing as well, is we have a deep, deep conviction around our data and around the potential benefit that it can provide to Huntington's disease patients. And we'll be doing everything possible to bring this to patients as quickly as we can. And that means continuing our interaction with the FDA as well as regulatory authorities outside the FDA. And I'll just say, you know, we're committed to the HD community, and we will continue to do everything that's possible.

Yeah, no, that makes sense. I know I want to talk about the upcoming Type B meeting, but maybe can we look back at a Type A meeting that happened in January? Maybe just walk us through, you already mentioned some of the limitations around pre-specifications, and obviously the data is single arm, so there's obviously some limitations there, but just Maybe walk us through what was the kind of main pushback that you were getting from the regulators. And related to it, were you under the impression that everybody was on the same page or were you under the impression that maybe the lower level staffers and reviewers versus the senior leadership had some sort of different views on that data set? Again, in the context of now the senior leadership being gone, was everybody on the same page or there was some sort of friction between the reviewers and senior leadership or how should you think about that?

Yeah, maybe the last part first. We don't know, obviously, everybody's individual view. That's just impossible for anybody to figure out. But what we do know is that there's been general consistency of the review team. So many of the people that we're interacting with were certainly in the room back in some of our earlier discussions around the accelerated approval pathway. So we know that these people understand the trajectory of the discussions, although we don't know anybody's individual view. The feedback from the Type A meeting and the pre-BLA meeting largely revolved around two aspects. One I mentioned previously, which was the lack of pre-specification. And we talked about, you know, that when we started this Phase I-II study back in 2018, being on the cutting edge, and that would have been incredibly difficult for us to pre-specify. In fact, in 2018, these registries were simply not where they are today, so it would have been nearly impossible to have pre-specified and had the foresight to be able to do that at the beginning of the study. Having said that, this is an analysis that we started doing even when just a few patients had crossed the two-year mark, and we had started to construct a propensity, score-adjusted methodology, an external control comparator back in 2023 and shared that analysis with the FDA in early 2024. So this approach has been something that we've consistently done, and we certainly had very little data and had conducted very little analysis at that point in time. The second part of the feedback was really a focus on the one-year U.S. study results. And just as a reminder, in the United States, we did a limited sham-controlled study with 10 sham patients and a blinding period that was only 12 months. So very, very different design. And the truth is that with enrolling patients with early manifest HD, there's just a limit of what you can be able to assess in a 12-month period of time. So even the even the untreated subjects didn't really show any meaningful signs of progression. So trying to trying to generate evidence that shows slowing of disease progression with that as a basis is is impossible. And quite frankly, any KOL in the space would tell you that it's just not enough of a follow-up period with a relatively slow-progressing disease. But nevertheless, I think there was a focus on that in the type A meeting, and that was the second part of the feedback.

Gotcha. That's awful. Maybe let's pivot to the type B meeting, which is obviously upcoming. It feels to me that in that Type B meeting, there's going to be two items on the agenda, again, from the outside. One, to talk about the confirmatory trial and how to design the confirmatory trial. And two, to talk about whether the data that is available today could potentially be approvable and lead to an accelerated approval. So one, is that correct? And then two, what percentage of your time are you going to spend on the confirmatory trial versus try to go back and persuade the regulators around the data that you already have in hands?

Yeah, so let me just start off with, you know, the strategy around the Type-E meeting. Again, you know, we, the H-Deep community is at the center of everything we do. We deeply believe in the data, and our sole mission is to bring this to patients as quickly as possible. Secondly, it is very important that we interact with the FDA around the four-year analysis. So the four-year analysis is going to have a data cutoff as of June 30th. We've told the FDA that we are doing this analysis, so we have to begin that process. We have to lock the database, and it's very important to us that we share the statistical analysis plan and the control protocol with the FDA as we did last year with the sole purpose of making sure that that analysis is as robust and interpretable as possible. So we have to meet with the FDA. We want to be on record and we want to get their constructive feedback. The second part of this is that the FDA in our type A meeting made a strong recommendation that we conduct a double blinded sham controlled study. We have never had any formal interaction with the FDA around the design, the appropriate design of a next study, whether that's confirmatory or a registrational study. And we think there are some important considerations that need to be evaluated in terms of feasibility and potential ethical matters. There have been statements made, You know, going back now a number of months that were not accurate, quite frankly, about the way in which a sham control protocol has been designed, could be designed. So we want to have a discussion with the review team and get an understanding of their perspective on this and where there might be design elements where there could be more flexibility.

Gotcha. Gotcha. That's helpful. So maybe in the context of everything you just said, and I appreciate it, this is a completely different approach, completely different molecules, a neural spell molecule, and works very differently from the molecule in the approach that you're using. Obviously, yours is intracranial delivery versus PTC and neural spell molecule. However, what was your reaction to their phase three trial that they're planning to run? I mean, they're planning to run a very, very large trial with 800 patients and I think primary endpoint in three years and placebo control, which I don't know if it would be feasible for your approach. Where do we draw the line between that versus a feasible trial that you can run that can substantiate the evidence that your drug is actually working in the context of a full approval that requires a placebo control trial here? Yeah.

I mean, it's obviously hard for me and maybe inappropriate for me to comment on their clinical development strategy. But what I will just say, because it's the elephant in the room, that when you have an oral, the patient risk, patient burden, and ethics around doing a randomized placebo study are just completely different than when you're doing a one-time administered, surgically infused therapy that, you know, currently requires 10 to 12 hours of anesthesia. So they are completely different. And we need to take those things very seriously, because in the end, you know, you have to, the patient and the impact on the patient should be front and center. The thing that you have to, so we have to look at that, right? Patient risk, patient burden, feasibility concerns, and that has to be coupled with the availability of clinical grade natural history data, right? I mean, there's multiple natural history databases, the largest of which is EnrollHD that currently has 30,000 participants and growing. It's a contemporaneous natural history registry. It is looking at the same endpoints that we would be using to evaluate therapeutic benefit. It is legitimately clinical grade, regulatory grade quality. It's required CHDI to be making hundreds of millions of dollars of investment. These are patients and family members that have put all of their time and effort for the sole purpose of exactly this, to gather evidence, to evaluate for regulatory purposes, and to have a one-time surgically administered therapy and the availability of this and then to say the only path forward is to do a sham-controlled study, I think that needs to be debated and discussed further than it has been thus far.

Sure, certainly in contrast with many other indications in CNS where we don't have the benefit of such a large data set, here we do, and so maybe there's an argument to be made that we should leverage that knowledge to compare data to natural history. Maybe if I I can go back to the four-year data coming, I believe, in Q3. What are you hoping to see there? I mean, at the end of the day, probably the most important endpoint here is still CUHDRS. And every time I look at your data, it looks to me that maybe like in one year, there's a half a point improvement in CUHDRS, maybe two years close to one, and maybe three years close to one and a half, right? So should we anticipate that the four-year data is going to be two, Or are you hoping to see maybe something better than that? Because maybe if your therapy is truly disease-modifying, you can see kind of an acceleration of that separation. It's like, how should we think about the data set in Q3?

Yeah, I mean, at the highest level, we want to see consistent findings, you know, from three years to four years. You know, I think our data at three years was generally considered to be, you know, best case or towards best case scenario. You know, we saw statistically significant, meaningful slowing of disease progression on the composite UHDRS. I think unexpectedly we even saw statistically significant slowing of disease on total functional capacity, which is, you know, I think probably one of the more important subdomains of CUHDRS for regulatory purposes. We saw evidence of dose-dependent slowing when you compared the low dose to the high dose. We saw general consistency across subdomain measures, and we also saw biomarker evidence of slowing of neurodegeneration, where we had NFL at three years kind of below baseline or at baseline. So I think, you know, while I won't put out a specific number that we want to hit, I think we generally want to see consistent findings that provides evidence of therapeutic benefit. And, of course, you know, every year that you provide in follow-up, there is the potential that the gap between treated patients and untreated patients becomes more clinically meaningful. So I think that is something that we'll be interested in seeing when we do the four-year evaluation.

That's super helpful. Maybe pivoting to ex-US, sounds like you had productive recent discussions with the regulators in the UK. What's the best way for us to rationalize why the U.K. regulators were more receptive than U.S. regulators?

Yeah, I mean, again, it's difficult for me to get into the mind's eye. But what I will tell you is, you know, there was a tremendous appreciation of the significant critical unmet medical need in Huntington's disease patients. You know, this is a rare, genetically defined disease, 100% penetrant. There's no debate about how devastating it is. And there's no disease-modifying treatments for these patients. And I think that the MHRA greatly understands that need and also understands the need to exercise regulatory flexibility in evaluating medicines. And, you know, while, you know, again, I don't want to put words in their mouth. I think it was it was very clear to them that that the evidence that we've provided is worthy of a review. And again, as to why, you know, the FDA has not come to that conclusion, at least historically, you know, we debate vigorously and obviously are very much hoping that perspective changes going forward. But it was a very, very different kind of discussion. We really applaud the regulators there for their forward thinking and very much looking forward to making that submission in the third quarter of this year. Gotcha.

Gotcha. That's helpful. Maybe walk us through the mechanics of, again, submission in the third quarter. What are the mechanics of unlocking some of the patients in the U.K., and what are the mechanics to unlock patients beyond the U.K. via the NAME Patients Program? You know, you guys have talked about Middle East and other pockets of the world. So, like, how should we think about the broader opportunity for Huntington outside the United States?

So I know the focus, a lot of the focus has been on the United States, but we really have, our commitment goes, it extends to the global Huntington's disease community. And there are, this is a global disease, and there's, you know, many, many patients, maybe even hundreds of thousands of patients in countries outside of the United States that also don't have access to any disease-modifying treatments. In the U.K. alone, I think the prevalence numbers are about 7,000 patients with Huntington's disease. There are pathways that can be leveraged, both including named patient programs and early access pathways. And then, of course, there's going to be more deliberate discussion that need to happen with the the ministries of health in those various countries there are some countries that can leverage the process or a potential approval in the united kingdom there are countries in the gulf that can leverage that there's also countries in the commonwealth the british commonwealth that can leverage that both in terms of name patient programs and in early access, and we're going to be doing everything we can to identify those opportunities and at the same time preserving the global value of AMT-130 in a careful way.

Got you. Got you. Makes sense. You mentioned 7,000 patients in the UK. Is that the TAM, like the actual patients you can potentially address, or is that a subset of that? Again, there's some pretty stringent inclusion criteria in your trial, like patients having preserved interventricular volumes and whatnot. So is 7,000 all of the patients out there, or the patients you think you can address with your therapy?

No, that's the prevalence number. And we're still in all these geographies working through exactly what the total addressable market is. But I would tell you that it is a meaningful opportunity in aggregate, even with the UK and the other countries that can be leveraging, even on a name patient and early access pathway. I mean, it is the ramping in some of these countries can take a little bit longer than it can in the United States, but nevertheless, in terms of peak total addressable market, it is meaningful. Sure.

Probably pushing my luck here, but how meaningful is meaningful? Outside the United States, again, I think we've seen Roche for Elevitas. They were actually able to do close to $100 million a quarter before, obviously, the program ran into talks and safety issues and whatnot. So is that a ballpark number that would be reasonable? Again, we don't know price. We don't know a lot of things yet. But is that a reasonable comp?

I think there is meaningful opportunities to maintain global value in terms of pricing. and I think there is a plethora of patients. I mean, I would say that even in the countries that we could be looking at, these are kind of tier one, tier two countries in the UK, the Gulf, Commonwealth, Latin America. These are tens of thousands of patients.

Gotcha, gotcha. Maybe in the last few minutes, let's pivot to TLE. Maybe just give us a little bit of a preview of the data that you're going to share, I think an upcoming medical meeting, June 18th and 19th, Epilepsy Foundation Conference. How many more patients' worth of data are we going to see? And what are some of the kind of key endpoints that we should be focused on?

Yeah, so we're going to be doing a presentation at an academic meeting later in the second quarter. It's going to include six months of follow-up on all six patients that were treated in the first dose cohort. Obviously, there will be a focus on safety and tolerability. but we'll also be looking at seizure frequency over the course of that six-month period of time from the first dose cohort. We're underway in dosing the second dose cohort. The data's early there, and so that data will be in a subsequent presentation.

Okay, that's helpful. Can you maybe remind us the route of administration here? I believe you're delivering the therapy to the hippocampus, so can you just maybe talk about what's the route of administrations and how easy would it be for a skilled neurosurgeon to actually deliver this? Like, just maybe walk us through the right administration here.

Yeah, so these are patients that have generally lesions that are specific to the mesial temporal lobe. The idea is to do a targeted, direct, precision-based administration directly into that structure of the brain. This is a single catheter infusion, small amount of material. It is a procedure that is easy. I do quote-unquote easy for a neurosurgeon to do and takes, I would say, meaningfully less time than it does in HD where you have to hit both the caudate and the putamen. So that's the route of administration.

Is there any biomarker that we can track for disindications? I know we're obviously focused on reduction in seizure, which is obviously very meaningful, and for better or for worse, these patients have seizures all the time, so a reduction in seizures should be relatively easy to capture in a relatively short period of time. Is there any biomarker that we can track to make sure that the drug is doing what it's supposed to do?

Yeah, it's hard. I think with doing a, you know, a single infusion deep within the hippocampus of less than 500 microliters, it's going to be difficult to evaluate any, you know, kinate reduction or suppression. um nfl which is a great biomarker in hd is really not a a biomarker in an epilepsy or validated one it's really looking at neuronal injury or death so it's not really an epilepsy biomarker uh you can do you can evaluate things like eeg but you know you would have to you know we're not doing continuous monitoring of eeg so there's not a lot of great biomarkers but as you pointed out

you know the the measuring of seizures and the evidence of that should be something that you can evaluate pretty closely and pretty accurately within a 12-month period of time yeah gotcha makes sense uh i know we're already out of time here maybe last questions on fabry just give us an update on that program maybe just remind us differentiations versus sangamore and then maybe remind us where you stand on dozing again my understanding is that mid-dose and the high dose has been paused for now, given the liver signal, but maybe just give us an update on that program.

Yeah, so on the, yeah, there are two patients that had significant adverse events. These are completely asymptomatic elevations of LFTs. You know, we've seen these actually before in our clinical evaluation of hemgenics. By protocol, they were designated as a dose-limiting tox where we would pause the study in order to evaluate and adjudicate those. I think we're confident that that will be adjudicated and dosing will resume relatively shortly. The study and the 11 patients that we've treated are actually going quite well. All of them are off of enzyme replacement therapy. We're seeing super physiological epidemiological elevations in alpha-gal that have never before been seen in a clinical study. We're seeing stable lyso-GB3, and we're looking forward to completing the dose escalation part of the study and then engaging with regulators about the potential for an accelerated pathway. Gotcha.

That's super helpful. Matt, I have a lot more questions, but no more time, so appreciate you joining us thanks everyone for joining us here at the rbc conference um all the best friends through your conference we'll talk soon thank you luca appreciate it