uniQure Stifel 2026 Healthcare Conference

from uniQure. Very topical time to be meeting with the team. Matt, we'll just kick it over to you. Feel free to introduce yourself, any initial comments about uniQure before we just dive into Q&A. Yeah, very excited to have you here, so thanks again.

No, thank you very much for having us here. We're delighted to be here. We are wrapping up a year where we've made substantial progress in our lead program in Huntington's disease, and we're full tilt focused on making 2027 our best year and a very impactful year for Huntington's patients going forward. Looking forward to getting into the discussion.

Terrific. Great. So yeah, you just had some recent news where the BLA for AMT-130 was accepted with priority review. You're also told that there's likely to be an AdCom. Just talk a little bit about that. Is that sort of in line with your expectations? Generally, any sort of high-level comments, then we can dig further?

Yeah, I mean, it's totally in line with our expectations. I think we've been interacting with research analysts and investors, getting asked these questions now for quite some time. We think that for a first disease-modifying treatment for Huntington's, one-time administered gene therapy, our expectations have been all along that we would have an AdCom, and quite frankly, we're delighted to have an opportunity to speak about our data in public and to have perspectives from various stakeholders, including the patient community.

Terrific. Yeah, no, totally makes sense. How do you prepare for an AdCom, and what types of questions are you expecting for the FDA to be bringing up? I guess, any sort of other commentary you can provide about, you've commented in the past about the rigor of the sensitivity analysis you've done with respect to your data in comparison to several natural history datasets. Just talk a little bit about that and sort of how you're preparing for the panel overall.

Yeah, I won't speculate on what kind of questions will be asked. That will obviously be up to the FDA. What I can talk about is just an enormous amount of preparation that we're going through. As I said, this is our base case expectation. We've already started kicking off planning and preparation for the AdCom months ago. We are engaged with one of the leading preparatory advisors to help us through this process. It incorporates a tremendous amount of work from all members of our team. It includes numerous mock panels that we go through. This is pretty standard stuff, but we obviously are taking this very, very seriously.

Yeah, in terms of the data, in our discussions with the FDA, we were very clear that one of the benefits that you have in Huntington's is probably some of the most prolific natural history data that exists. There are multiple different natural history studies, the largest of which is called Enroll-HD. Enroll-HD, at the time that we did our original analysis back in 2025, had more than 30,000 participants. It is a natural history study that has been going on for 10 years. CHDI is the sponsor of the study. They've invested a tremendous amount of money in it. It is clinical-grade quality data. This is not just slapping data together. I mean, this is run almost as a clinical trial. So very high-quality data, very significant amount of subjects. It is concurrent, so it is ongoing. It is still accruing patients.

It was a natural source of data. Having said that, we recognize that in developing an external control, you're making a lot of assumptions. So, as part of our pre-specified sensitivity analyses, we sensitized a number of those assumptions. So that includes looking at other sources of data. We looked at TRACK-HD, which is another natural history dataset that has about one-tenth the number of patients, but we looked at that. We also looked at different covariates. When you develop a propensity score, you baseline patients and you match patients based on what's called covariates. We use eight. We also looked at looking at four different covariates. There's different ways of matching, different assumptions you can make. We sensitize that. So we've done a lot of work on the natural history. We've shared our methodologies with the FDA along the process.

And really, since those discussions that we had in 2025, we tried to keep a lot of those the same going forward.

The data that supports our BLA is based on the data that was reviewed with the FDA back in 2025, and it's in accordance with the statistical analysis plan that was shared with the FDA back earlier that year as well.

Terrific. I think that's a good segue just to touch on, this wasn't sort of a straight path with respect to regulatory. FDA had changed their tone under prior leadership. There's now new leadership. Just talk overall just about how comfortable you are in general, and generally speaking, what was sort of the context of the meeting that got the FDA to turn back and allow you guys to file, or got you comfortable in at least filing the BLA?

Yeah, I mean, what I can do is go through a little bit of the recent history. So we, of course, in January 2026, had our Type A meeting with the FDA after our pre-BLA meeting. In that meeting, the FDA informed us that the data that we had presented thus far, the 36-month data, could not serve as the primary analysis to support a BLA, and they strongly recommended that we move forward with a double-blinded sham-controlled phase III study. We have all along the way felt that that was not in the best interest of patients with HD who have no disease-modifying treatments available. And we were going to continue to try to interact with the FDA to advance the program.

We had a Type B meeting in June of this year, and in that meeting was FDA leadership, and they made it clear to us in that meeting that they do believe that the data that we had presented could support the primary basis of a BLA submission. It is hard for us to get into the mind's eye of what might have changed, but obviously, we have never given up on this. We are completely committed to this patient population, and we very, very rapidly moved. We really never stopped preparing for the BLA, planning for success. We very quickly turned that into a final BLA submission, and just recently, last week, announced the acceptance, so we are delighted.

Terrific. Before that BLA acceptance, you also recently shared some updated data from AMT-130, both four-year data following up the three-year data from last year, as well as a couple additional patients, a three-year data set, right? Can you just talk a little bit about that? What were the results there? And can have some follow-ups too.