uniQure Q2 2025 Earnings Call Transcript

Quartr
Provided by Quartr
July 29, 2025

Key Takeaways

  • Positive Sentiment: AMT-130 received breakthrough therapy and RMAT designations and achieved FDA alignment on its statistical analysis and CMC requirements for a planned 2026 BLA submission.
  • Positive Sentiment: Top-line pivotal data for AMT-130 and initial AMT-191 Fabry data are expected in September, which could support accelerated approval and commercial launch planning.
  • Positive Sentiment: AMT-260 showed a 92% seizure reduction in the first mesial temporal lobe epilepsy patient over five months with no serious adverse events, spurring strong investigator interest.
  • Negative Sentiment: Q2 revenue fell to $5.3 M from $11.1 M a year ago, driven by lower collaboration and contract manufacturing revenues.
  • Positive Sentiment: Cash and investments totaling $377 M provide runway into 2027 to support clinical programs and the planned AMT-130 launch.
AI Generated. May Contain Errors.
Earnings Conference Call
uniQure Q2 2025
00:00 / 00:00

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Operator

Good day and thank you for standing by. Welcome to the UniCure Second Quarter twenty twenty five Earnings Conference Call. At this time, participants are in a listen only mode. After the speakers' presentation, there will be a question and answer session. To ask a question during the session, you will need to press 11 on your telephone.

Operator

You will then hear an automated message advising your hand is raised. To withdraw your question, please press 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Kiara Roussa, Senior Director of Investor Relations. Please go ahead.

Chiara Russo
Chiara Russo
Senior Director - IR at uniQure

Good morning, and thank you for joining us for Unicare's 2025 earnings call. Earlier this morning, Unicare released its financial results for the 2025, and our press release is available on the Investors and Media section of our website at unicure.com. Our 10 Q was also filed with the SEC earlier this morning. Joining me on the call today are Matt Kavista, Chief Executive Walid Abhisab, Chief Medical Officer and Christian Klempt, Chief Financial Officer.

Chiara Russo
Chiara Russo
Senior Director - IR at uniQure

After our formal remarks, we will open up the call for Q and A. Before we begin, please note that we will be making forward looking statements during this investor call. All statements other than statements of historical fact are forward looking statements. They are based on management's beliefs and assumptions and on information available to management only as of the date of this conference call. Your actual results could differ materially from those anticipated in these forward looking statements for many reasons, including without limitation, the factors described in UniCare's most recent SEC filings.

Chiara Russo
Chiara Russo
Senior Director - IR at uniQure

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 Kavista, Unicur's CEO.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Thanks, Kiara, and good morning, everyone. Thank you for joining today's second quarter conference call. The 2025 has been tremendously productive for the company as we advance AMT-one hundred thirty towards potentially becoming the first disease modifying therapy for Huntington's disease. Our momentum is strong across four key areas: clinical advancement, regulatory alignment, BLA readiness and commercial launch preparation. We also made advancements across our broader clinical pipeline, including AMT-one hundred ninety one for Fabry disease, AMT-two sixty for mesial temporal lobe epilepsy and AMT-one hundred sixty two for SOD1 ALS.

Matt Kapusta
Matt Kapusta
CEO at uniQure

With pivotal top line data from AMT130 and initial clinical data from AMT191 in Fabry, both expected in September, we believe the 2025 is shaping up to be an eventful period for Unicure. Turning to AMT-one hundred thirty. In Q2, we continued to have productive interactions with the FDA, including receipt of breakthrough therapy designation in April and further regulatory alignment. AMT-one hundred thirty remains the only investigational therapy in Huntington's disease to have either breakthrough therapy designation or regenerative medicine advanced therapy or RMAT designation granted by the FDA. In June, we achieved alignment with the FDA on both our statistical analysis plan and CMC requirements for a planned BLA submission in the 2026.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Our primary efficacy analysis will compare the three year change in CUHDRS in high dose patients to a propensity score matched external control arm using data from the ENROL HD natural history study. In addition, the FDA agreed that we can leverage our experience from Hemgenics in validating the AMT-one 130 manufacturing process and that our process performance qualification can be limited to one such batch, supplemented by additional commercial scale GMP batches. Following FDA guidance, we've made significant progress in preparing for the planned BLA submission. Manufacturing of two scale pre PPQ GMP batches is now complete and we've initiated our formal PPQ campaign. We also recently submitted our final statistical analysis plan to the FDA, which Waleed will discuss in more detail shortly.

Matt Kapusta
Matt Kapusta
CEO at uniQure

On the commercial planning front, we continue to make disciplined investments in preparation for a potential 2026 launch. In June, we appointed an experienced leader, Kylie O'Keefe, as Chief Customer and Strategy Officer, and our HR team is actively recruiting key roles across medical affairs, market access, commercial operations, other critical areas. The team is making strong progress on an integrated launch strategy, and we look forward to sharing more details in the future. Now turning to our broader pipeline. In May, we shared encouraging early data from the first patient treated with AMT260 for mesial temporal lobe epilepsy.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Over the first five months of follow-up, the patient experienced a ninety two percent reduction in seizure frequency with no significant adverse events. This early result has sparked strong interest among investigators and the epilepsy community. I'm pleased to say that we have 14 clinical sites in The US that continue to screen patients for this study. During the second quarter, we also continued to advance our Fabry and SOD1 ALS studies and look forward to presenting initial Fabry data at the IC IEM Conference in early September. Overall, I'm incredibly proud of the team's execution and dedication towards advancing these important therapies.

Matt Kapusta
Matt Kapusta
CEO at uniQure

In the 2025, we delivered on several key goals and remain on track for what we believe could be a transformational second half marked by meaningful data updates, regulatory progress and continued momentum towards the plan BLA submission of AMT-one 130. I will now turn the call over to Walid to provide a more detailed clinical update. Walid?

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Thank you, Matt. Good morning and good afternoon, everyone. During the 2025, we continued to make meaningful advancement across our portfolio of clinical stage gene therapies. Let me start with AMT-one hundred thirty. In April, AMT-one hundred thirty was granted breakthrough therapy designation by the FDA.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

This recognition, a first in Huntington's disease, was based on the phase onetwo data showing the potential to slow disease progression and underscored both the urgent need for effective treatments for Huntington's disease and the potential therapeutic benefits of AMT-one hundred thirty. As you know, our recent FDA interactions have been highly productive. Following two Type B meetings in the first and second quarter, we announced in July alignment with the agency on the statistical analysis plan and CMC requirements for AMT130. The FDA agreed that the three year change in CUA CRS measured against the propensity score adjusted external control constructed using ENROLL HD dataset could serve as the registrational endpoint for an accelerated approval BLA. The agency also endorsed our CMC strategy, stating that it should be possible to validate the AMP130 manufacturing process by leveraging prior knowledge and experience from Hemgenics, Unicure's approved commercial gene therapy for hemophilia B.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

This approach supplemented with data from additional full scale GMP batches and a single successful PPQ run may be sufficient to support process validation for the BLA submission. As Matt just mentioned, we have completed those GMP batches and the PPQ campaign is currently underway. As stated in the press release this morning, we have submitted the final SAP using a propensity score matched external control derived from the ENDROL HD data set for the primary analysis. A number of additional analyses, including a propensity score weighted external control will be submitted as sensitivity and supplemental analyses. This update reflects an alignment with the FDA's stated preference and recommendation for propensity score matched natural history controls.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

The FDA will receive both the propensity score matched and propensity score weighted analysis as disclosed previously. Turning now to clinical progress, I'm incredibly pleased to report that the AMT-one hundred thirty clinical team has successfully completed the June 30 cutoff date for the three year data, keeping us on track for the expected September data update. I'm also pleased to announce a fourth cohort in this Phase onetwo trial of ANT-one hundred thirty expected to initiate in the third quarter. This open label single arm US study will evaluate safety of the high dose of ANT-one hundred thirty in at least six patients with lower striatal volumes. Patients who would have previously been excluded based on the criteria of a minimal striatal volume can now be considered potentially expanding access to treatment.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

We expect to have full enrollment by the 2025. Finally, in September, we plan to present top line data of our Phase onetwo of AMT-one hundred thirty. We currently plan to disclose safety and tolerability data through thirty six months follow-up, as well as other top line data, including CUA CRS and TFC at both dose levels compared to a propensity score match natural history control. We also plan on providing CSF NFL data at both doses compared to baseline at thirty six months. Moving on to AMT260 for mesial temporal epilepsy.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

In late May, we shared initial data from the first subject in the gentle phase one2a study at the Epilepsy Therapies and Diagnostic Development Symposium. We observed a ninety two percent reduction in seizure frequency over the first five months of follow-up with no serious adverse events. While additional follow-up on this first trial participant and enrollment of additional participants in this trial are needed, this case study provides an early signal that suggests our miRNA based GRYK2 targeted gene therapy can potentially suppress seizure activity in this type of patients. This early data has generated enthusiasm among investigators and trial sites, as well as interest within the broader epilepsy community, which is eager for differentiated novel treatment options. So trial recruitment remains challenging.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

I'm very proud to say that additional sites have been activated and we expect to have additional patients enrolled before the end of the year. Moving to AMT-one hundred ninety one for Fabry disease, the Phase one2a clinical trial continues to enroll patients and we expect to present initial safety and exploratory efficacy data at the twenty twenty five International Congress of Inborn Errors of Metabolism or ICIEM Conference on September 5 in Kyoto, Japan. Lastly, I'll touch on AMC-one hundred sixty two for SOD1 ALS. We continue to dose patients in the Phase onetwo Episode one clinical trial, and we anticipate sharing the study's initial safety and biomarker data in the 2026. Now, I will turn the call over to Christian for a financial update. Christian?

Christian Klemt
Christian Klemt
CFO at uniQure

Thank you, Molly. I'll start off by sharing the financial highlights of the 2025. Please refer to the earnings press release issued this morning and our quarterly filing for additional details. Revenue for the first quarter was $5,300,000 compared to $11,100,000 in the same period 2024. The decrease of $5,800,000 in revenue resulted from a $3,400,000 increase in license revenue, a decrease of $7,100,000 from collaboration revenue, and a decrease of $2,100,000 from contract manufacturing of allogeneic or CSO bearing.

Christian Klemt
Christian Klemt
CFO at uniQure

As noted in the first quarter, following the divestment of the Lexicon facility in July 2024, revenue from contract manufacturing is recorded net of cost within other expenses. Cost of contract manufacturing revenues were nil for the three months ended 06/30/2025, compared to $7,200,000 for the same period 2024. Again, following the divestment of the Lexington facility in July, cost of contract manufacturing is recorded net of revenue and other expenses. Research and development expenses were $35,400,000 for the three months ended 06/30/2025, compared to $33,700,000 during the same period in '24. The $1,700,000 increase was related to an increase of $6,300,000 in external program spend and the $4,000,000 higher expenses related to an increase in fair value of contingent consideration.

Christian Klemt
Christian Klemt
CFO at uniQure

This was offset by a decrease of $4,700,000 in employee related expenses, a decrease of 2,100,000 in facility expenses, and a $1,800,000 decrease in costs related to preclinical supplies. Selling, general and administrative expenses were $13,500,000 for the three months ended 06/30/2025, compared to $15,800,000 during the same period 2024. The $2,300,000 decrease was primarily related to a $1,600,000 decrease in employee related expenses and a $600,000 decrease in professional fees compared to the prior year period. Cash, cash equivalents and investment securities totaled $377,000,000 as of 06/30/2025, compared to $367,500,000 as of 12/31/2024. The increase is primarily related to the net proceeds of $80,500,000 from our first quarter follow on offering.

Christian Klemt
Christian Klemt
CFO at uniQure

With this strong balance sheet, we believe Unicur is well positioned to execute its clinical and operational priorities, including the planned commercialization of AMG one hundred thirty in The U. S. In 2026. We expect cash, cash equivalents, and investment securities will be sufficient to fund operations into the 2027. I'll now turn the call back over to Matt.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Thanks for the update, Christian. As you've heard today, our strong execution during the 2025 has positioned us for what we believe will be an exciting and pivotal second half of the year. We've achieved regulatory alignment on an accelerated approval pathway for AMT-one hundred thirty, submitted our final statistical analysis plan, initiated our PPQ campaign and continue to advance key BLA preparation activities. We very much look forward to presenting top line pivotal data anticipated in September, which we expect will support a planned BLA submission in the 2026 and if approved, commence a U. S.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Commercial launch later that year. At the same time, we're progressing our broader pipeline with encouraging early data in mesial temporal lobe epilepsy and initial Fabry data on track for September. Our mission remains clear to deliver transformative therapies for patients with serious unmet needs. We are focused, well resourced and energized for the opportunities ahead and we look forward to keeping you updated on our progress in the months to come. With that, we will open the call to take questions from our research analysts. Operator, please proceed.

Operator

Our first question comes from Debjit Chattopadhyay with Guggenheim. Your line is open.

Debjit Chattopadhyay
Senior Managing Director at Guggenheim Partners

Hey, good morning and thanks for taking my question.

Debjit Chattopadhyay
Senior Managing Director at Guggenheim Partners

I have one and a follow-up as well. So number one, does the FDA expect a minimum threshold for clinical benefit versus the enrolled HD on C UHDRS?

Matt Kapusta
Matt Kapusta
CEO at uniQure

Walid, do wanna answer that one?

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Sure. In discussions with the FDA, minimum clinical effect has not been requested, nor has it been included in the SAP plan. You know, having said that, we will be, you know, submitting the three year data, which we expect that will show a substantial level of evidence that would support accelerated approval after the FDA review.

Debjit Chattopadhyay
Senior Managing Director at Guggenheim Partners

Appreciate that. And our understanding is that the company has written feedback. So how certain are you that the FDA senior leadership won't run on what's already been communicated to the company?

Matt Kapusta
Matt Kapusta
CEO at uniQure

Yeah, Debjit, obviously, you know, we were watching what's going on in the space. We know what's publicly available in those situations. Each of these situations are very nuanced. All of our interactions with the FDA have been very encouraging and very supportive. And as we've said in the past numerous times, we have very clear and unambiguous feedback with the FDA.

Matt Kapusta
Matt Kapusta
CEO at uniQure

In terms of our situation, it is different meaningfully in so much that we're moving forward with clinical outcomes data and long term clinical outcomes data as opposed to relying a surrogate biomarker. So we believe this is a robust approach. We're focused on controlling and executing on what we can control, and we're feeling very optimistic about our path forward.

Debjit Chattopadhyay
Senior Managing Director at Guggenheim Partners

Thank you. And I'll

Operator

Thank you. Our next question comes from Joseph Schwartz with Leerink Partners. Your line is open.

Jenny Gonzalez-Armenta
Equity Research Associate at Leerink Partners

Hi guys, this is Jenny on for Joe. Thank you for taking our question. Could you walk us through the AMT one hundred thirty procedure and what this would look like from a patient's perspective, including the time commitment? And how are you thinking about who would be appropriate for the surgery and how should we think about the commercial population? Do you think there's a particular subset of patients who are more likely to be early adopters? Thank you.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Wally, you wanna talk about the procedure?

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Sure. The procedure is really one that is not complicated technically. I mean, if you speak to neurosurgeons who've done any neurosurgical administration to treat, you know, tumors or any deep brain stimulation, this is really a fairly low complexity procedure. At least that's how the neurosurgeons describe it to us. Patients usually get an MRI ahead of time so that we can plan the trajectory.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

The neurosurgeon will plan the trajectory based on the MRI, because of course there's specific anatomical differences for each patient that the surgeon needs to take into consideration. And on the day of the surgery, the patients come in to the hospital in the morning and then they get admitted to neurosurgery and using MRI guided registration, essentially probes are inserted in the brain under direct visualization of the MRI. And the infusion, there will be drilling of a hole in the brain through which the catheter is infused, is introduced. And then through direct visualization, we observe the infusion of the product, which is mixed with the contrast material that is MRI compatible gadolinium. And that way the neurosurgeon can observe live as they're administering the therapy that it's actually reaching its target.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

That's a very important aspect in what we do. Now, the infusion has to occur at a slow rate to make sure that the product diffuses appropriately to the right structure. And that actually is what consumes most of the time. So a lot of the time during the procedure, which has to be done six times because we administer three times on each side of the brain, is what it takes actually most of the time. And usually that takes a number of hours at the end of which essentially the patient wakes up and usually they stay like twenty four hours, I believe, and then they will be discharged.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Often they tend to recover very quickly because again, it's a very minimal, how should I say, very minimally invasive from the perspective of the size of the probe that are introduced and often patients, within a few days, they get back to work. At least that's been our experience in our trial. And I'll go back to you, Matt, for details on the target patient population and commercial question.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Yeah, I mean, I think the reality is there's nothing for these patients. There's no disease modifying therapy. And so I believe that the overwhelming majority of patients that are eligible are going to become informed about it, and I think seriously consider therapy. In terms of our inclusion criteria, we're largely looking at stage two and stage three patients, which are typically patients that are considered early manifest. So they have developed some form of symptomology, and they've been tested and confirmed genetically that they have Huntington's disease that will become 100% penetrant.

Matt Kapusta
Matt Kapusta
CEO at uniQure

So that's definitely going to be our focus. And I think it's going to be, as I said, it's going to be something that now that there is at least a treatment option, that it's hard to imagine that all or a majority of all patients are going to seriously consider and become informed about our therapy.

Jenny Gonzalez-Armenta
Equity Research Associate at Leerink Partners

Thank you. That's really helpful.

Operator

Thank you. Our next question comes from Paul Matteis with Stifel. Your line is open.

Paul Matteis
Paul Matteis
Managing Director, Head of Therapeutics Research at Stifel Financial Corp

Great. Good morning. Thanks for taking my questions. We noticed this morning that you said you're going to be using propensity matched in this analysis, not propensity weighted. Can you just talk about where that comes from?

Paul Matteis
Paul Matteis
Managing Director, Head of Therapeutics Research at Stifel Financial Corp

Is that something that the FDA requested? And then specifically, how does that compare to the data that we saw in the last cut in 2024? If it's a different methodology than what we're going to see here, is this going to be apples and oranges? Is the 80% number for 01/1930 still stand? And then if you don't mind, I just have one follow-up. Thank you.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Walid, do you want go and answer that?

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Thanks. Yeah, thanks, Paul. Yeah, we've indicated previously when we reported back after meeting with the FDA that the FDA's stated preference was for propensity score matching. We've also consulted with our external statistical experts. And when we took all of these into consideration, we decided to submit the SAP that's aligned with the FDA preference using propensity score matching as a primary endpoint.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Having said that, the agency will also continue to receive both the propensity score matching and the propensity score weighting analysis, just as we stated before. Now, in constructing the natural history database, as we were evaluating, excuse me, the most appropriate natural history database to use, we had to construct the annual decline over a period of three years of patients using variety of methodologies, propensity score rating matching, exact matching, number of these. And using the ENDROL database, we found that the propensity score methodology in whichever form is quite robust, leading very similar estimate of decline after three years, regardless of the methodologies. So to answer your question, I will not expect that the results will be materially different if we use propensity score matching propensity score rating and considering the FDA's preference, we decided to go that route, be more aligned with them, But we will be submitting both anyway.

Paul Matteis
Paul Matteis
Managing Director, Head of Therapeutics Research at Stifel Financial Corp

Okay. Thank you. That's super helpful. And then look, I know this is extraordinarily subjective and ultimately in Huntington's right, there's nothing. But how are you guys thinking about the bar on disease slowing in this three year analysis?

Paul Matteis
Paul Matteis
Managing Director, Head of Therapeutics Research at Stifel Financial Corp

Look, again, that Huntington's doesn't have any disease modifying treatments, I would think you'd want the data to hold up to some degree, right? Just first of all, for the best of the drug and second of all, to be confident in your regulatory alignment. So investors and analysts are trying to draw this line. How would you draw this line?

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Sorry, I assume I'm going to continue. I'm just going to give it to you. Apologies.

Matt Kapusta
Matt Kapusta
CEO at uniQure

No, go ahead, Waleed.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Yeah, I mean, I think we're asked that question a lot. It's an important question. Honestly, as you said, there's nothing for these patients. Matt mentioned that before. When we talk to a number of KOLs, what they tell us is, look, anything that would reduce the disease progression by twenty five to thirty percent would be great.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

It would add potentially many years of quality of life to these patients who have nothing. But, you know, from our perspective, you know, just like you said, we would like our data to continue to show a meaningful slowing of disease progression that will be something that the agency will consider appropriate for approval, but also the patients will find clinically meaningful. That is, you know, we believe in our mechanism of action. We saw the data at two years. We feel optimistic that the three year data will continue to show a meaningful improvement that will both satisfy the patients, but also the FDA.

Operator

Thank you. Our next question comes from Joseph Thome with TD Cowen. Your line is open.

Joseph Thome
Managing Director, Senior Biotechnology Analyst at TD Cowen

Hi there. Good morning. Thank you for taking my questions. I have one question and one follow-up if I can. I guess just given the back and forth with Sarepta over the course of this week, has that changed at all your thinking on how you're approaching the launch in any way, whether you want to do a stage launch, just target number of surgeons, be a little bit more cautious at the beginning or how you're thinking about that? Obviously, so many differences between disease states and age and everything like that. But I guess are there any learnings that you've taken from the past week? And then second, do you expect there to be a minimal straddle volume on the label? I only ask because I noticed you're initiating a fourth cohort with smaller volume.

Joseph Thome
Managing Director, Senior Biotechnology Analyst at TD Cowen

So kind of just thinking that that's going be a formal label expansion or if this would be more just a use guideline for clinicians in the field. Thank you.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Yeah, well maybe I'll take the first one, you take the second one. So, I mean, honestly, we've always operated in a way where patient safety is our utmost priority. It's not like anything going on in the sector is going to change that view.

Matt Kapusta
Matt Kapusta
CEO at uniQure

I think we've always thought that for AMT130 that there are going to be, at the time of launch, centers of excellence that have experience with the surgical procedure that conducting these procedures. And it's something that we're going to be continually monitoring as we launch the product. But at the same time, we treated 45 patients. I think we really believe that AMT-one hundred thirty is generally safe and well tolerated. I'll also mention that our administration of AMT-one hundred thirty

Matt Kapusta
Matt Kapusta
CEO at uniQure

So the systemic exposure that occurs when we administer AMT-one hundred thirty is meaningfully less than a gene therapy that is systemically administered. And we have just simply not seen any liver toxicity associated with AMT-one hundred thirty. We're also utilizing an AMD-five vector that has been studied with systemic administration vis a vis hemgenics. And we've also not seen any significant adverse events associated with hemgenics or AAV5 in that context as well, even with systemic administration. So, it's very important to understand these technical differences with administration, but nothing's going to change our view that patient safety is always going to be at the top of our priorities.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Okay. So on the striatal volume, just maybe taking a step back, the way this came to be was, as the study was initially signed some six years ago or so, out of the abundance of caution, we wanted to make sure that we have a serrated volume that would be large enough so we can safely administer the product to these patients. But over the years, and as accumulated a lot of experience with more than 44, total of 45 intraparenchymal administrations to date, the experience that we accumulated with our neurosurgeons and in discussions with them, we've decided that we should be relaxing these criteria and now evaluating an approach where we will use the neurosurgeons clinical judgment, whether they can reach the targeted structure safely without fixing a specific minimum volume. And in order for us to study that, we needed to include patients who have otherwise would have been excluded from a trial, those with lower survival volume to start generating safety data with this. Now, whether this will be in the label or not, those discussions have not taken place with the FDA.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

That would be something that would have to occur later in the review process. Of course, generating these data and depending on the outcome of the safety profile of this, those will be included in the safety update and will be part of our discussions with the agency. But it's premature right now to be able speculate or give guidance as to what we think the label would look like.

Operator

Thank you. Our next question comes from Sushila Hernandez with Van Lanschhoff Kempen.

Sushila Hernandez
Equity Research Analyst at Van Lanschot Kempen Investment Banking

Yes. Thank you for taking my question. Also, just to follow-up on the fourth cohort. So what do you hope to expect to see in the patient population? And then second question, what are the next steps for AMT two sixty? Are you expecting to add more sites? Thank you.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Madam, suppose I'll take both. Right?

Matt Kapusta
Matt Kapusta
CEO at uniQure

Yeah. Go ahead.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

So with the fourth cohort, the expectations in the short term is to document the safety of the procedure that we can administer this safely that the neurosurgeons that we have and the system that we have in place could be able to evaluate whether we can safely administer AMT-one hundred thirty for those who would have otherwise been excluded from our trial because they would have a lower cellular volume. The system is in place, it operates well and we can administer it. And then of course we will be monitoring them for efficacy and so on and so forth. But I personally do not foresee where there would be any difference, you know, once we establish that the AMT-one hundred thirty is actually, you know, effective in slowing disease progression. There's no reason for this to be different based on an arbitrary cutoff of serrano volume.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

In terms of AMT260, yes, indeed, as Matt said, we have increased the number of sites. We now have 14 active. There's a lot of activity since we've disclosed the data on that first patient with the very positive results. They've been received very positively. We've seen a very significant uptick in screening activities and we really do feel quite confident that we will be getting a number of additional patients in the second half of the year.

Operator

Thank you. Our next question comes from Patrick Trucchio with H. C. Wainwright. Your line is open.

Patrick Trucchio
Managing Director at H.C. Wainwright & Co.

Good morning, everyone, and congratulations on the project on the progress. This is Luis in for Patrick. First question, just thinking ahead of any are there any differences? Do you expect any differences from regulatory path to approval in Europe versus The U. S?

Patrick Trucchio
Managing Director at H.C. Wainwright & Co.

And then on the 01/1930? And on 01/1960, how should we think about the planned Phase II portion look like in terms of patients? Will we plan to enroll the same disease stage patients with or also include nonlinearable patients as well? Thank you so much.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Yeah, just I'll maybe take the first one, Walid, and you can address the second one. So, we have not yet met with EMA to solicit scientific advice with respect to the registrational path forward. Our focus right now is on The US, and of course, we'll expect to have the three year data presented, which we think could be also important information to furnish EMA when we have those scientific advice discussions. So, we'll look to have them in the near term. And once we do, we'll make sure we provide an update to the market.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Regarding AMT260, in terms of design of the Phase II study, it's premature to discuss that. The reality is that we do Phase I to learn from it so that that will also dictate the design of the subsequent trial. But in terms of the patient population, we start with those on the non dominant because that way you establish the risk benefit profile and then you start branching out to those with dominant disease. I think the next natural step will be also to look at bilateral. The reality is that it's those with dominant and bilateral is where the high unmet need is because those would be unlikely to benefit from invasive therapy like ablation, laser ablation or resection surgery.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

But that's kind of the thinking that we have around expansion as we advance in the program.

Operator

Thank you. Our next question comes from Eliana Merle with UBS. Your line is open.

Analyst

Hey, this is Jasmine on for Eli. Thank you for taking So first, can you give any color on what you plan to talk about and learn from the pre BLA meeting with the FDA in 4Q? And will we get an update after this meeting? And then secondly, on the Huntington's commercial opportunity, how many sites in The U. S.

Analyst

Are capable of doing the administration procedure? And based on the study enrollment criteria, can you give an estimate of the prevalence of patients that would be eligible in The U. S? Thank you.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Yeah, so I'll answer the last question first, Walid, and then you can answer the first question, if that's okay. So, I mean, in terms of the commercial potential, there's thirty five thousand patients that are currently diagnosed with Huntington's disease. And then there's probably three times as many people that have Huntington's disease but have not been genetically confirmed because there's obviously nothing for those patients. Our view is that there's going to be we'll provide, obviously, more detail on this, but the overwhelming majority of the patients that are diagnosed have stage two and stage three, because typically the diagnosis of Huntington's disease happens once there's symptom onset. So there's going to be many thousands of patients that, in our view, are going to be eligible for the procedure.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Now, the last part of this was the number of sites that are capable of doing the procedure. Just to be very clear, this is not a novel procedure. This is a very standard procedure for a neurosurgeon. There's probably somewhere between fifty and fifty five sites that have the neurosurgical expertise and the imaging equipment to be able to do this procedure. We don't even think we need to be in every one of those centers to address the market.

Matt Kapusta
Matt Kapusta
CEO at uniQure

And certainly at launch, there's going to be a center of excellence strategy. And then I'll hand it over to Waleed to answer the first part of your question.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Yep, thank you. So for the PBLA meeting, we will be meeting with the FDA of course, and sharing with them the top line results from our phase three data and also as well as any updates on CMC activities and discuss with them. There are some elements of the typical technical procedures and tactical questions and logistics that way, whether the data that we have is acceptable to them and whether the totality of the data would support moving forward and submitting the BLA. That's the plan. And as usual, after we have meetings with the regulators, once we receive feedback, we usually have always been communicating back to you guys the outcome of these meetings. So we will do that again.

Operator

Thank you. Our next question comes from Luca Eci with RBC. Your line is open.

Luca Issi
Luca Issi
Senior Biotechnology Analyst at RBC Capital Markets

Great. Thanks so much for taking my question. Maybe circling back on regulatory, have you actually met or maybe had some informal conversations with Vinay Prasad? I think many investors argue that the final decision to approve this drug will ultimately come down from the very senior leadership at CBER similar to Sarepta with Peter Marks. So I was just curious if you already had had interactions with him and if you have any insights that you can share there. And then maybe second, can you just maybe clarify what do you think that the ongoing data for Huntington can lead to full approval given your chasing function? Or is it fair for us to assume that this is gonna lead to accelerated approval that's still the base case scenario? And if so, if it is, it's under approval, can you maybe talk through how you're thinking about the timing of starting a confirmatory trial? Thanks so much.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Yeah, so our last interaction with the FDA occurred in late April. Vinay was appointed he didn't attend our meeting, but he was in charge at that point in time. I was fortunate enough to attend the CEO listening tour with Doctors Makary and Doctor. Prasad in Boston. So I had a chance to meet with him and to understand his perspectives and approaches.

Matt Kapusta
Matt Kapusta
CEO at uniQure

What he made very clear is that he is very interested and willing to evaluate additional data sets other than randomized controlled studies. Doctor. Prasad is epidemiologist by training, and he deeply understands the use of external controls and synthetic cohorts in order to evaluate therapeutic benefit. So I'm confident that given the statements that Doctor. Prasad has made, that he's open and supportive of faster accelerated pathways for cell and gene therapies that are addressing severe unmet needs like Huntington's disease.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Just in terms of the full approval, accelerated approval, our base case, of course, and what we're going to be seeking is accelerated approval. Having said that, the FDA did make it very clear to us that the phase onetwo study results can be used and leveraged to support full approval. So to the extent that additional evidence is going to be required for confirmation associated with full approval, you know, and that data can be incremental, to what we already have established and generated from the Phase III study thus far.

Operator

Thank you. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open.

Lydia Erdman
Lydia Erdman
Biotech Equity Research Analyst at Goldman Sachs

Hi, good morning. This is Lydia on for Salveen. Thanks so much for taking our questions. Just another on AMT-one 100 thirty ahead of the September update. Could you just speak to how consistent the two point five year data has been versus the two year data we saw last year? Thank you so much.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Waleed?

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Yes. Thanks, Tajiya. We have not conducted any formal analysis on the data since the one with the June 30 cutoff of 2024, which served the basis for the November 2024 meeting with the FDA. So we do not have the data that you are describing. The next analysis will be the one at June 30 cutoff of this year, which we will be communicating to you guys in September, the three year data cutoff.

Operator

Thank you. Our next question comes from Yanan Zhu with Wells Fargo Securities. Your line is open.

Yanan Zhu
Yanan Zhu
Senior Analyst, Biotechnology Equity Research at Wells Fargo

Great. Thanks for taking our questions. On the topic of propensity matched versus propensity score weighted analysis methodologies, I was wondering in the data you have submitted to FDA for your SAP proposal, could you comment on whether those two methodologies, data look similar with each other? And I also am wondering whether the approach of which one to use affects the sample size that you can use for the external control arm.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Well, Lee, why don't you go ahead and answer those questions?

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Thanks, Matt. Yeah, very good question. So to be clear, the SAP that we submitted to the agency does not include the results, right? It includes the methodologies. What I was trying to describe earlier is in our, as we are evaluating the natural history protocol, to evaluate which natural history database, enroll, track, HD, predict HD, would be most appropriate to be compared to, we've employed various propensity score methodologies to essentially select the patients that meet the baseline criteria for our subjects in our trial, and observe what is the decline after three years using these various methodologies.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

And what gives us a lot of confidence, both in the methodology itself, the propensity score methodology, is the fact that whether we use propensity score weighting or matching, and by the way, there are multiple ways to match. You can have optimal matching, you can have greedy matching, full matching. I can go on and on, and we can go into a lot of details maybe offline if you want to. Those will generate various different levels of size of control. But at the end, the estimate around the score in CUH CRS or in TFC that the decline after three years tend to be generally very similar and not materially different.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

And that's what gives us confidence that these methodologies will yield similar results once you compare our data and subtract the three year change in our data from the change in the natural history control. But that analysis comparing our theory of data to the has not been done yet. So I need to be very clear on that. In terms of the size of the external control, yes, of course. The propensity score weighting is the one that utilizes essentially all of the controls that you have available that meet the criteria for your trial.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

In the case of a Role HD, it's somewhere around 3,000. That's the propensity score weighting, it uses variety of methodology to be able to allow to include everybody, which contributes to a varying degree based on how closely they resemble your sample. Matching uses a proportion of those patients. And again, there are different types of matching. You can have a very simple matching one to one.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

You have matching one of your patients to maybe twenty, thirty of the control, depending on how large the control group is. And there are many ways that you can tailor this optimal matching or full matching and so on and so forth. And those could lead somewhere around maybe 200, 300, if you want to do a 20 or 30 fold, your patients in your trial to 600, if you want to do full matching. And those are the types of different types of methodologies. I apologize, I might've gone a bit too much into details, but I like that topic so much that I can speak on it for a long time.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

But you should rest assured that the estimate of change after three years tend to be fairly similar regardless of the method you use. And that gives us very good confidence that the results will not be materially different when we compare them to the change in our patients.

Operator

Thank you. Our next question comes from Sami Corwin with William Blair. Your line is open.

Sami Corwin
Research Analyst at William Blair

Good morning. Congrats on the update. Thanks for taking my questions. I guess I was curious if FDA provided any guidance as to what they're looking for with Nf L for it to be used as a supportive biomarker. If they're kind of looking to see if levels return to or below baseline and that'll be sufficient or if there'll need to be some specific magnitude of reduction beyond baseline shown.

Sami Corwin
Research Analyst at William Blair

And then I had a follow-up. Was curious, you know, we've seen with some other gene gene therapy trials, one of the key limiting factors for commercialization seems to be the availability of beds as well as hospital staff. And if you think that may be a limiting factor for the launch of AMP-one 130 as well. Thank you.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Wally, you wanna answer the first one?

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Thanks, Matt. Yeah. So to be clear, NFL topic has not been a topic of discussion with the agency. We were the one who brought it up back in November when we asked the question actually, whether NFL data could be supportive. And the FDA said yes, that the NFL data could be supportive, but there's been no discussion at all about, you know, whether there should be any correlation with the COHCRS or what change should be from baseline or anything.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

The difficulty with this is that, and I think it's a relevant question as well, relevant to the update that we're going have at three years, that when we presented data to you last time, we used two year data because there are data available from an external study looking at longitudinal two year change from baseline in CSF and FL levels. Unfortunately, no such data exists for the three years time point, which will limit interpretation of our upcoming data. So it becomes a little bit difficult to figure out, okay, so what does good look like? We know what bad looks like in NFL, you know, when you have increases and so on and so forth. We know that patients usually go up by about 15% a year.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

And clearly our data at two years show that both doses were below baseline. So we were looking forward to see what our three year data would look like, but it would be a bit difficult because we don't have an external competitor. Going back to your original question, there has been no specific discussions with the FDA about what the Nf L data should look like. But our, we were, I guess our expectations are and we're confident in our data that the Nf L data will continue to support our primary clinical endpoint of serious CRS.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Yeah, and maybe just the second question. We don't think capacity of beds is something that is going to be a significant factor in the launch of our product. I mean, remember, this not cell therapy where patients have to be preconditioned, immunoblated, spend weeks in the hospital. I've often talked about the last patient we treated earlier this year was admitted to the hospital on a Tuesday morning, completed the procedure on Tuesday, and was discharged from the hospital Wednesday morning. So I don't think that's a factor that we think is going to be a material one for our launch.

Operator

Thank you. Our next question comes from Kristen Kluska with Cantor Fitzgerald. Your line is open.

Richard Miller
VP - Biotech Equity Research at Cantor Fitzgerald

Hi, this is Rick Miller on for Kristen. Thanks for taking our question. Just one from us. Can you kind of walk us through the natural history comparators that can sort of inform the external comparator that we could see in the September update? And how should and should we be expecting to see enroll HD comparators at that time or any other analyses? Thank you.

Matt Kapusta
Matt Kapusta
CEO at uniQure

Walid?

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

Thank you. Yes, so as part of our meeting with the FDA back in November, we discussed with the FDA how to proceed to evaluate the various natural history databases that we could use. And we asked whether we should include ENDROL HD because it has a very large database. And the FDA encouraged us to do so, which we did. And the follow-up meeting that we had with them back in April, we walked them through all of our assessments, comparing the natural history for a variety of reasons, which I could perhaps take offline and walk you through this.

Walid Abi-Saab
Walid Abi-Saab
Chief Medical Officer at uniQure

The ENDRAWL HD was deemed the one that's the best fit for us to compare to. We made that proposal and the FDA agreed with us that ENDRAWL HD will be the comparison. So the data that you will see in September will be a comparison of our data to the ENDRAWL HD three year data using propensity score matching as a primary endpoint. As again, as I said before, we will be including a number of other sensitivity analyses, including propensity score weighting as well and submit to the FDA.

Operator

This concludes the question and answer session and today's conference call. Thank you for participating. You may now disconnect.

Executives
Analysts
    • Debjit Chattopadhyay
      Senior Managing Director at Guggenheim Partners
    • Jenny Gonzalez-Armenta
      Equity Research Associate at Leerink Partners
    • Paul Matteis
      Managing Director, Head of Therapeutics Research at Stifel Financial Corp
    • Joseph Thome
      Managing Director, Senior Biotechnology Analyst at TD Cowen
    • Sushila Hernandez
      Equity Research Analyst at Van Lanschot Kempen Investment Banking
    • Patrick Trucchio
      Managing Director at H.C. Wainwright & Co.
    • Analyst
    • Luca Issi
      Senior Biotechnology Analyst at RBC Capital Markets
    • Lydia Erdman
      Biotech Equity Research Analyst at Goldman Sachs
    • Yanan Zhu
      Senior Analyst, Biotechnology Equity Research at Wells Fargo
    • Sami Corwin
      Research Analyst at William Blair
    • Richard Miller
      VP - Biotech Equity Research at Cantor Fitzgerald
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