Q3 2025 UniQure NV Earnings Call

Speaker #1: To ask a question at this time, you'll need to press star followed by the number one on your telephone keypad. As a reminder, this conference call is being recorded.

Speaker #1: I would now like to turn the call over to Chiara Russo, Senior Director of Investor Relations. Thank you. Please go ahead.

Speaker #2: Good morning and thank you for joining us for uniQure's third quarter of 2025 earnings call. Earlier this morning, uniQure released its financial results for the third quarter of 2025, and our press release is available on the investors and media section of our website at uniQure.com.

Speaker #2: Our 10Q was also filed with the SEC earlier today. Joining me on the call this morning, are Matt Kapusta, Chief Executive Officer, Dr. Walid Abi, Chief Medical Officer, Kylie O'Keefe, Chief Customer and Strategy Officer, and Christian Klemt, Chief Financial Officer.

Speaker #2: After our formal remarks, we'll open the call up for Q&A. Before we begin, please know that we will be making forward-looking statements during this investor call.

Speaker #2: All statements other than statements of historical fact are forward-looking statements. They are based on management's beliefs and assumptions and information available to management only as of the date of this conference call.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: Now, let me introduce Matt Kapusta. UniQure's CEO.

Speaker #3: Thanks, Chiara. Good morning, everyone. Thank you for joining today's third quarter conference call. As you know, in the third quarter, we announced positive top-line data from our pivotal phase one two study, of AMT 130 and Huntington's disease.

Speaker #3: The first gene therapy to demonstrate statistically significant slowing of disease progression in Huntington's disease. These groundbreaking results represent an important milestone not only for uniQure, but also for patients and families who have long awaited a potential disease-modifying therapy.

Speaker #3: As previously disclosed, we met with the FDA in late October to review our data and discuss the potential submission of a BLA for AMT 130.

Speaker #3: Based on discussions at the meeting, we believe the FDA currently no longer agrees that the data from the Phase 1/2 studies of AMT-130, in comparison to an external control, may be adequate to provide primary evidence in support of a BLA submission.

Speaker #3: Consequently, the timing of a BLA submission for AMT 130 is now uncertain. This feedback represents a notable shift from prior communications with the FDA during multiple type B meetings over the past year.

Speaker #3: We plan to urgently engage with the FDA to discuss next steps, and we expect to receive the formal meeting minutes within the next 30 days.

Speaker #3: While the latest FDA feedback is certainly surprising and disappointing, we continue to strongly believe that AMT-130 has the potential to provide significant benefit to patients.

Speaker #3: We believe the data presented to date widely recognized as the most compelling ever generated in Huntington's disease, provides substantial evidence of therapeutic effect. Every year, thousands of Americans die because of Huntington's disease, and thousands more are newly diagnosed.

Speaker #3: We believe AMT 130 has the potential to significantly slow disease progression and exemplifies the type of transformative innovation in rare diseases the FDA has pledged to support.

Speaker #3: We remain fully committed to our partners, investigators, and most importantly, to Huntington's patients and their families and to work in collaboratively with the FDA to bring this therapy to Huntington's patients in the US as rapidly as possible.

Speaker #3: We will continue to act with urgency, transparency, and discipline as we work to deliver on the promise of gene therapy to transform lives. I will now turn the call over to Walid.

Speaker #4: Thank you, Matt. Good morning and good afternoon, everyone. I would like to start by reiterating that the recent feedback from discussions at our pre-BLA meeting does not change our belief in the data.

Speaker #4: We continue to believe that AMT 130 represents the most compelling therapeutic data set generated in Huntington's disease to date. The true highlight of the third quarter was the positive top-line data from our pivotal phase one two studies of AMT 130 and Huntington's disease.

Speaker #4: Before I go on, I want to thank our employees, investigators, partners, and especially the patients and families who have been participating in the CHCI Natural History Studies in our clinical studies.

Speaker #4: It is thanks to their deep commitment and efforts that we have been able to achieve such progress. In September, we reported top-line data of the high dose of AMT 130 demonstrated a statistically significant 75% slowing of disease progression as measured by the composite unified Huntington's disease rating scale, or CUHRS, at the three years compared to a propensity score matched external control derived from the enrolled HD natural data set leading the pivotal studies pre-specified primary endpoint.

Speaker #4: Equally important, patients treated with high-dose AMT-130 demonstrated a statistically significant 60% slowing of disease progression at three years, as measured by the total functional capacity at key secondary endpoints.

Speaker #4: Moreover, serial responder fluid neurofilament light chain is a well-characterized and supportive biomarker measuring neurodegeneration was below baseline at 36 months in patients treated with high dose AMT 130.

Speaker #4: The top-line data from the high dose were supported by consistent results in multiple sensitivity analyses, demonstrating the robustness of these findings. We believe these results provide the first clinical evidence that gene therapy can potentially alter the course of Huntington's disease.

Speaker #4: In keeping with the spirit of full transparency, for the scientific and medical communities, we are working diligently on a comprehensive publication strategy starting with publishing our full data results in a well-respected peer-reviewed medical journal.

Speaker #4: As Matt noted earlier, we met with the FDA for a pre-BLA meeting in October, and based on discussions at the meeting, we believe that the FDA currently no longer agrees that data from the phase one two studies of AMT 130 in comparison to an external control may be adequate to provide primary evidence and support of a BLA submission.

Speaker #4: This feedback was unexpected. We believe AMT 130 has the potential to significantly slow disease progression, and we plan to urgently interact with the FDA and are fully committed to working with the agency to find an expeditious path forward.

Speaker #4: Turning now to AMT 260 for mesial temporal lobe epilepsy. In May, we announced initial data from the first treated patients with five months of follow-up.

Speaker #4: At that time, we observed promising reduction in seizure frequency over the first five months of follow-up with no serious adverse events. This data generated enthusiasm among investigators, and potential patients.

Speaker #4: We have now activated 17 recruiting sites in the United States and completed enrollment of the first three patients in the first cohort. Following a favorable review by the independent data monitoring committee, recruitment has now expanded to mesial temporal lobe epilepsy in the dominant hemisphere, and the initiation of a second cohort at a higher dose for the protocol.

Speaker #4: We expect to provide updated data from the study in the first half of 2026. Moving to Fabry disease, in September, we also reported encouraging results from the ongoing phase one two A trial of AMT 191, which were presented at the International Congress of Inborn Errors of Metabolism in Kyoto.

Speaker #4: Across the four patients treated in the first cohort, we observed supraphysiological alpha-gal A enzyme activity below patients successfully withdrawn from enzyme replacement therapy while maintaining stable plasma lysoGB3 levels through the July 24, 2025, data cutoff date.

Speaker #4: These results, together with a manageable safety and tolerability profile, reinforce the potential of AMT-191 to be a one-time dose gene therapy for Fabry disease.

Speaker #4: Enrollment in the second lower dose cohort has been completed, with a third cohort currently enrolling. We expect to share updated data in the first half of 2026.

Speaker #4: I will now touch on some additional pipeline updates. We have voluntarily paused enrollment in the phase one two episode one trial of AMT 162 for SOD1 ALS based on the recommendation of the independent data monitoring committee following a September 2025 review of the preliminary data related to the safety and efficacy of AMT 162 in the context of a dose-limiting toxicity that was observed in one patient in the second cohort.

Speaker #4: This event resulted in a serious adverse event determined to be related to AMT 162. At this time, we will continue to collect and evaluate data from the patients treated with AMT 162.

Speaker #4: To summarize, the third quarter marked a milestone for AMT 130 with a positive top-line data from our pivotal phase one two studies. The recent feedback from the FDA has introduced uncertainty into the path forward, but we believe in our data and we are focused on working with the agency to define the next steps.

Speaker #4: Now, I will turn the call over to Kylie to discuss our recent patient advocacy work. Kylie?

Speaker #2: Thank you, Wilead. As both Matt and Wilead have said, our commitment to the HD community remains unwavering. Following our September data announcement, we experienced a groundswell of hope and support from patients, patient advocacy groups, clinicians, and scientists alike.

Speaker #2: We understand and deeply appreciate the concern and disappointment expressed by the community following our announcement last week, regarding the pre-BLA meeting with the FDA.

Speaker #2: We are reminded, however, that every step of this journey—including moments like this—reflects the seriousness of our mission and the importance of getting this right for HD patients.

Speaker #2: During this period, commercial and medical teams continue to thoughtfully plan and execute with discipline and focus. Our primary focus continues to be on stakeholder engagement and education, including treatment centers of excellence, payers, and patient advocacy, to best position us to be fully prepared for a strong and informed potential launch of AMT 130.

Speaker #2: Concurrently, as we have a focus on building the foundational strategy for the US market for a potential launch of AMT 130, we are also looking to additional potential markets outside of the US, such as the EU and the UK.

Speaker #2: The feedback we are receiving from the physician and patient community reinforces both the high level of unmet need and the enthusiasm for the potential of AMT 130.

Speaker #2: Their support continues to motivate our team, and we remain committed to maintaining open communication and collaborating with the community as we plan next steps.

Speaker #2: We believe deeply in our science. The data we have generated to date and the impact of the therapy could have for HD patients. Now, I will turn the call over to Christian for a financial update.

Speaker #2: Christian?

Speaker #3: Thank you, Kylie. I'll now be sharing financial highlights of the third quarter of 2025. Please refer to the earnings press release issued this morning and our quarterly filing of the SEC first additional detail.

Speaker #3: Revenue for the three months ended September 30, 2025, was $3.7 million, compared to $2.3 million in the same period in 2024. The increase of $1.4 million in revenue resulted from a $1.5 million increase in license revenues and a decrease of $0.1 million from collaboration revenues.

Speaker #3: Cost of contract manufacturing revenues were nil for the three months ended September 30, 2025, compared to $0.8 million for the same period in 2024.

Speaker #3: Following the divestment of the Lexic facility in July 2024, cost of contract manufacturing revenues are recorded net of revenue within our expenses. Research and development expenses were $34.4 million for the three months ended September 30, 2025, compared to $30.6 million during the same period in 2024.

Speaker #3: The $3.8 million increase was driven by an increase of $10.1 million in direct research and development expenses of which $6.6 million related to the preparation for the BLA submission of AMT 130, offset by a decrease of $3.4 million in severance costs and the $3 million decrease in costs related to disposables, facilities, and other expenses.

Speaker #3: Selling in general and administrative expenses were $19.4 million for the three months ended September 30, 2025, compared to $11.6 million during the same period in 2024.

Speaker #3: The $7.8 million increase was primarily related to $2.4 million increase in employee relief-related expenses and the $4.9 million increase in professional fees including $3 million in clinical care to support the preparation of potential conversation of AMT 130 in the United States.

Speaker #3: Cash, cash equivalents, and investment securities totaled $649.2 million as of September 30, 2025, compared to $376.5 million as of December 31, 2024. The increase is primarily related to the net proceeds of $404.2 million from our public offerings this year.

Speaker #3: With this strong balance sheet, we believe UniQure is well positioned to execute its clinical and operational priorities. We expect cash, cash equivalents, and investment securities will be sufficient to fund operations into 2029.

Speaker #3: I'll now turn the call back over to Matt.

Speaker #4: Thank you, Christian. As you've heard today, the third quarter of 2025 was a pivotal one for UniQure, and we continue to have strong conviction in both the compelling data set and therapeutic potential for AMT 130.

Speaker #4: Our focus now is on working with the FDA to clarify next steps and determine the most expeditious path to bring AMT 130 to patients in the US.

Speaker #4: In parallel, we will plan to advance discussions with other regulatory agencies including those in the European Union and the United Kingdom. As we move forward, we do so with confidence in our science, clarity in our mission, and a deep determination to make a meaningful difference for patients and families affected by Huntington's disease.

Um and and um, and that's why we we have really strong confidence, uh, in in the results that we've seen and but but regardless, if you also look at the numerical change from Baseline in our patient population and compare it to a number of data that's being published by uh, a number of studies that are run in that space. And in comp comparable patients, you see that the magnitude of the change from Baseline at 3 years is very small compared to 1 with expect and, uh, and Placebo or untreated subjects.

Our next question comes from UEI ear from mizuho. Please go ahead. Your line is open.

Hey guys. Yeah, thanks for taking the question, maybe. Um, just help us understand a little bit about what happened in AMT 162? Could you kind of remind us, um, what whether this was the ve, what the vectors was and whether of a similar to the other um, pipeline studies and um, along with that, uh, what was the dose difference between the first cohort and the second cohort, thanks.

A known address event, particularly for, uh, this route of administration.

And uh, we knew and we were monitoring very carefully with this. Unfortunately, we've seen that at the middle dose which I can tell you is about 3 fold higher than the low dose and and as a result uh we back down. Uh but now we're monitoring uh, the data and to see over time how this will evolve and we will have a discussion with the experts and the idmc to determine the uh the next steps for this program. Uh we should be able to come back in the first half of next year with some answers on this.

And and just to be clear, you're, this is a, a, a totally different capsid than what we use in our other programs and a and a and a different, uh, mode of administration.

Our next question comes from salvian Richter from Goldman Sachs. Please go ahead. Your line is open

Hi good morning. This is Lydia on for Saline. Thanks so much for taking our question. Um could you just talk to what details? You hope to learn from the final meeting minutes here in the next 30 days. Thanks so much.

Yeah, I think um, what I would say is we don't want to speculate on what will be in the minutes. We assume that they'll reflect um.

Um, mostly the conversation that we had, uh, uh, in Washington DC, um, but but most importantly, you know, we hope it'll give a sense of, uh, the concerns that the FDA has, um, and, uh, and give us an outline for how to address those concerns in the subsequent meeting with the FDA.

Trauma. Joseph Holmes, from TD Cowen, please go ahead. Your line is open.

Hi there. Good morning. And thank you for taking my question. Um, I guess, are you able to kind of confirm that prior meeting minute documents did confirm the ability to file for accelerated approval based on the CDRs? Maybe like the meeting minutes from the RAT meeting at the end of 2024. Was that officially documented in what they sent to you? And maybe how much detail do they go into in these meeting minute documents around the definition of the Cisco analysis plan and the external comparator? Thank you.

Yes. So, I can confirm that in our, in our November 2024, multidisciplinary meeting with the FDA and the written comments that we received, uh, the FDA stated that the data from The Phase 1, 2 study in comparison to an external control, may serve as the primary basis of a bla submission. Uh, they also confirmed that the composite, uh, DRS, uh, would be considered an acceptable intermediate clinical endpoint to support accelerated approval, um, in that particular meeting. Uh, the, the they didn't get into specifics on the statistical analysis plan, uh, but had recommended that, we prespecified, stats plan, and that was discussed in detail, as well as the Natural History protocol in our April, 2025 meeting with the FDA.

Our next question.

comes from Luca EC from

Oh great. Yeah, thanks so much for taking a question.

Maybe Matt, I got to appreciate the situation and still fluid here. But can you just talk about what needs to happen from here? Over the next few weeks, in order for you to continue to invest capital in Huntington? I guess what? I'm trying to ask here is, where do you draw the line between continued to fight this versus, just give up like any call their much appreciated.

Yeah, I wouldn't characterize this as a fight. Um, I think that we are um 100% committed to continuing to collaborate and partner with the FDA to determine an expedited path.

Uh, uh, to submit a bla. Um, I think we strongly believe that AMT-130 can meaningfully benefit patients.

I think feel that we have um what is considered to be the most compelling data set in the field of Huntington's uh with 3 years of clinical outcomes data showing a meaningful slowing of disease progression

Um, and we think that, you know, if there are, uh, concerns or issues, uh, that they ought to be addressed in a, uh, in, in a proper review. And so, you know, we will continue to work with the FDA to address any concerns they have

Uh that we're going to be focused on and we are committed. Uh we we believe we have a drug that works. We have a a patient

We are a group that has an urgent need, and we're committed to doing everything we can to bring this to them as quickly as possible.

Our next question comes from Janet.

Fargo, please.

Great. Thanks for uh, taking our questions. Uh, just uh, first a quick clarification for the um ALS program is it uh, interesting delivery. Um, and is the if so is the AE. Uh, the dorsal. Root gangling AE, uh, previously known to this route. Um, then maybe just on the uh, uh, the Hockinson program just wondering, uh, can you characterize how motivated or mobilized? The patient and Doctor Community is uh honestly the issue and how that could uh uh help remove the issue around. Thank you.

Okay. Well do you want to answer the first 1 and then I'll kick it? I'll kick it to Kylie to do the second.

Thanks much. Yeah. Um, the first question, the answer is yes to both. So it's interesting call delivery and its dorsal, root ganglia toxicity. Uh, which again, as I said, uh unfortunately the associated with this mode of administration and and uh, and we we know this with a risk. So yes.

Over to you Kylie.

Thanks Wy. Yeah, as as I just said, the patient and physician Community are

Very motivated. They have a huge unmet medical need and uh,

Collaboratively working together to look at how to how to move this forward. I think 1 of the things that's important is we received a big

expression of Hope and excitement coming out of the data. And then to, to have this disappointment, a few weeks later is, is a bit of an emotional roller coaster for the community, but I think they're they're working together to look forward and say, how do we bring this therapy to patients?

Our next question comes from Patrick tukio from HC Wayne Wright. Please go ahead, your line is open.

Hi, this is Arabella on for Patrick. I was just wondering if you could clarify, if you've received any EMA or um, mhra preliminary feedback on accepting the same data set in external control for AMT 130, as primary evidence and could you see X, us submissions, preceding ahead of FDA approval,

Only do you want to answer that?

Sure, um, so we have not yet engaged in in the UK or EMA we mhra or, or EMA, uh, that is the plan uh, to go next to your prioritizing the FDA. But I will say that we, we are committed to work with uh, the FDA also to continue to, to find a path forward. And and also with with other Regulatory Agencies and um, we will advance as quickly as possible on all these fronts to bring, uh, the therapy to patients as quickly as possible.

For any additional questions.

Paul Matthias from Stifel, please go ahead. Your line is open.

Uh, great thanks for putting me in, um, as it relates to the meeting again, answer, whatever you're comfortable with. But, you know, given that your dialogue here, I guess, as I understand it has been with a relatively similar group of people across, um, the spring meeting and then last November last year when they came out and told you that they didn't think this path was no longer supportive, uh, of a bla. Did you ask them why and what exactly had changed and then just separately, can you clarify for us what specific data Have you shared with the FDA at this point? And have they seen more data from this 3 year analysis than we have? Thank you so much.

Yeah, Paul. Um, you know, unfortunately we're not going to be able to comment on the details of the specific meeting. Um, but uh, you know, we we we do hope for clarity. Once we do receive minutes and to the extent that there are material updates, we will uh, we will endeavor to update, uh, investors and analysts.

um,

so I think that's the answer to your first question. And then the second question,

Oh okay. Yeah, on the data. Uh know the data that was submitted to the FDA was was consistent with the data that that we've shared publicly a number of weeks ago. Obviously there's

Some additional data, like sensitivity analyses, that that haven't been presented. Uh, but there was no new follow-up or or additional data, uh, that was provided to the agency.

We have no further questions. This will conclude today's question and answer session and today's call. You may now disconnect.