uniQure - Earnings Call - Q3 2025

Executive Summary

• Q3 revenue of $3.7M increased by $1.4M y/y on higher license revenue, but operating loss widened and non-operating expense surged, driving a net loss of $80.5M ($1.38/share) versus a $44.4M loss ($0.91/share) in Q3’24.
• Management disclosed a key regulatory setback: preliminary FDA pre-BLA feedback indicates external-control Phase I/II data for AMT-130 may not be adequate as primary BLA evidence, rendering BLA timing unclear; the company plans urgent FDA engagement.
• Balance sheet was fortified by an upsized follow-on (net proceeds ≈$323.7M) and debt refinancing, ending Q3 with $694.2M in cash, cash equivalents and current investment securities, extending cash runway into 2029.
• Key pipeline milestones: AMT-130 high-dose showed statistically significant 75% slowing on cUHDRS and 60% on TFC at 36 months; AMT-260 Phase I/IIa cohort enrollment advanced; AMT-191 initial Phase I/IIa data showed 27–208x α-Gal A increases and ERT withdrawal; AMT-162 enrollment paused after a DLT-related SAE in one patient.
• Stock reaction catalyst: the FDA stance shift on AMT-130’s evidentiary approach and any follow-on FDA minutes/next steps disclosed by management are likely to dominate near-term narrative and positioning.

What Went Well and What Went Wrong

What Went Well

• AMT-130 achieved statistically significant efficacy at 36 months: 75% slowing of disease progression on cUHDRS (p=0.003) and 60% on TFC (p=0.033); NfL −8.2% at 36 months; safety generally manageable with no new drug-related SAEs since December 2022.
• Strengthened liquidity and runway: ~$323.7M net offering proceeds (gross ~$345M) and debt refinancing increased cash and investments to $694.2M at quarter-end; runway now into 2029.
• Management conviction and commercialization readiness: “The third quarter… marked a defining moment… AMT-130… demonstrated statistically significant slowing of disease progression,” while continuing commercial planning in U.S. and exploring EU/UK pathways.

What Went Wrong

• Regulatory surprise: FDA preliminary pre-BLA feedback no longer supports using Phase I/II external-control data as primary BLA evidence; BLA timing now unclear, a shift from prior 2024–H1’25 alignments.
• Financials deteriorated: Non-operating items swung to a $20.9M expense (FX headwinds, warrant liability FV change, issuance costs), contributing to a wider net loss of $80.5M in Q3.
• Pipeline hiccup: AMT-162 (SOD1 ALS) enrollment paused following a dose-limiting toxicity leading to a related SAE in one patient; continued data collection underway.

Transcript

Operator (participant)

Good morning and welcome to UniQure's Third Quarter 2025 Earnings Call. All participants are in a listen-only mode. After the speaker's remarks, we will conduct a question-and-answer session. 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. I would now like to turn the call over to Kiara Russo, Senior Director of Investor Relations. Thank you. Please go ahead.

Chiara Russo (Senior Director of Investor Relations)

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

Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the factors described in uniQure's most recent SEC filings. Given these risks, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these statements even if new information becomes available in the future. Now, let me introduce Matt Kapusta, uniQure's CEO.

Matt Kapusta (CEO)

Thanks, Kiara, and 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 I-II study of AMT-130 in Huntington's disease, 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. 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. Based on discussions at the meeting, we believe the FDA currently no longer agrees that the data from the phase I-II studies of AMT-130, in comparison to an external control, may be adequate to provide primary evidence in support of a BLA submission.

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. 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. 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. 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.

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. We remain fully committed to our partners, investigators, and most importantly, to Huntington's patients and their families, and to working collaboratively with the FDA to bring this therapy to Huntington's patients in the U.S. as rapidly as possible. 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.

Walid Abi-Saab (CMO)

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. 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 I-II studies of AMT-130 in Huntington's disease. Before I go on, I want to thank our employees, investigators, partners, and especially the patients and families who have been participating in the Enroll-HD natural history studies and our clinical studies. 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 that 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 cUHDRS, at three years compared to a propensity score matched external control derived from the Enroll-HD natural data set, meeting the pivotal study's pre-specified primary endpoint. 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, a key secondary endpoint. Moreover, serous bowel fluid, neurofilament light chain, a well-characterized and supportive biomarker measuring neurodegeneration, was below baseline at 36 months in patients treated with high-dose AMT-130. 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. 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. 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 I-II studies of AMT-130 in comparison to an external control may be adequate to provide primary evidence in support of a BLA submission. This feedback was unexpected. We believe AMT-130 has the potential to significantly slow disease progression.

We plan to urgently interact with the FDA and are fully committed to working with the agency to find an expeditious path forward. 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. 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. 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 per the protocol.

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 I-IIA trial of AMT-191, which were presented at the International Congress of Inborn Errors of Metabolism in Kyoto. Across the four patients treated in the first cohort, we observed supra-physiological alpha-galA enzyme activity with all patients successfully withdrawn from enzyme replacement therapy while maintaining stable plasma lyso-Gb3 levels through the July 24, 2025, data cutoff date. 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. 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. I will now touch on some additional pipeline updates.

We have voluntarily paused enrollment in the phase I-II, Episode I 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. 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. To summarize, the third quarter marked a milestone for AMT-130 with the positive top-line data from our pivotal phase I-II 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.

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

Kylie O’Keefe (Chief Customer and Strategy Officer)

Thank you, Walid. As both Matt and Walid 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. 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. 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. 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.

Concurrently, as we have a focus on building the foundational strategy for the U.S. market for a potential launch of AMT-130, we are also looking to additional potential markets outside of the U.S., such as the European Union and the U.K. 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. 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. We believe deeply in our science, the data we have generated to date, and the impact this therapy could have for HD patients. Now, I will turn the call over to Christian for a financial update. Christian?

Christian Klempt (CFO)

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 for additional detail. 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 in a $1.5 million increase in license revenues and a decrease of $0.1 million from collaboration revenues. 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. Following the divestment of the Lexic facility in July 2024, cost of contract manufacturing revenues are recorded net of revenue within other 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. 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 cost and a $3 million decrease in costs related to disposables, facilities, and other expenses. Selling, 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. The $7.8 million increase was primarily related to a $2.4 million increase in employee-related expenses and a $4.9 million increase in professional fees, including $3 million incrementally to support the preparation of potential commercialization of AMT-130 in the United States.

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. 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. I'll now turn the call back over to Matt.

Matt Kapusta (CEO)

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. 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 U.S. 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.

Before we open up for questions, I'd like to note that because we have not yet received the final meeting minutes from our pre-BLA meeting with the FDA, and out of respect for the agency and our shared goal of advancing AMT-130 for patients with Huntington's disease, we will strictly limit our responses about that meeting to the information disclosed in our November 3, 2025, press release. We appreciate your understanding and are happy to address other questions you may have. Operator, please go ahead and open the call.

Operator (participant)

Thank you. As a reminder to ask a question, please press star, followed by the number one on your telephone keypad. In the interest of time, we ask that analysts please limit themselves to one question. Thank you. Our first question today comes from Joe Schwartz from Leerink Partners. Please go ahead. Your line is open.

Joe Schwartz (Senior Research Analyst)

Great. Thanks very much for taking my question. The treatment effect you've reported out to three years is quite large. I'm wondering, to what extent have you stress-tested the results in order to see what a very conservative rendition of the results would look like? For example, could you remind us how you constructed the external control arm to consider whether there were any potential sources of bias?

Matt Kapusta (CEO)

Hey. Thanks, Joe. Walid, do you want to answer that one?

Walid Abi-Saab (CMO)

Hey, guys. Can you hear me?

Matt Kapusta (CEO)

Yep.

Walid Abi-Saab (CMO)

You can. I'm sorry. I wasn't sure if I'm muted or not.

Matt Kapusta (CEO)

Yes, we can.

Walid Abi-Saab (CMO)

Yeah. Thank you. All right. Thanks for the question. Actually, what we have done is essentially follow a rigorous way to do the propensity score matching with Enroll-HD. I think Enroll-HD lends itself to provide fairly robust data because of the size of it. You get very good matches. What we have done in discussion with the FDA is prepared a series of sensitivity testing evaluating propensity score matching using different types of matching with propensity score weighting. We've also looked at a smaller number of variables, which was part of an SAP that we have proposed much earlier in the process during the RMAT application. We looked at regional differences. We looked at comorbidities based on medication and so on and so forth.

Last but not least, we compared to track and predict a sensitivity analysis, again, as part of the pre-agreed types of sensitivity analyses with the agency. Across a variety of these analyses, the results were very consistent, demonstrating the robustness of these findings. That is why we have really strong confidence in the results that we've seen. 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 a number of studies that are run in that space in comparable patients, you see that the magnitude of the change from baseline at three years is very small compared to one we'd expect in placebo or untreated subjects.

Operator (participant)

Our next question comes from Yui Iya from Mizuho. Please go ahead. Your line is open.

Hey, guys. Yeah. Thanks for taking the question. Maybe just help us understand a little bit about what happened in AMT-162. Could you kind of remind us what the vectors were and whether it was similar to the other pipeline studies? Along with that, what was the dose difference between the first cohort and the second cohort? Thanks.

Walid Abi-Saab (CMO)

Yeah. Thanks for the question. We have not quite disclosed all of the data about the dose so far. With this product, we have seen previously in a compassionate use that was the case of dorsal root ganglia toxicity. It is a known adverse event, particularly for this route of administration. We knew and we were monitoring very carefully with this. Unfortunately, we have seen that at the middle dose, which I can tell you is about three-fold higher than the low dose. As a result, we backed down. Now we are monitoring the data to see over time how this will evolve. We will have a discussion with the experts and the IDMC to determine the next steps for this program. We should be able to come back in the first half of next year with some answers on this.

Matt Kapusta (CEO)

Just to be clear, this is a totally different capset than what we use in our other programs and a different mode of administration.

Operator (participant)

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

Hi. Good morning. This is Lydia, on for Salveen. Thanks so much for taking our question. 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.

Matt Kapusta (CEO)

Yeah. I think what I would say is we don't want to speculate on what will be in the minutes. We assume that they'll reflect mostly the conversation that we had in Washington, D.C. Most importantly, we hope it'll give a sense of the concerns that the FDA has and give us an outline for how to address those concerns in a subsequent meeting with the FDA.

Operator (participant)

Our next question comes from Joseph Thome from TD Cowen. Please go ahead. Your line is open.

Joseph Thome (Managing Director and, Senior Biotechnology Equity Research Analyst)

Hi there. Good morning. Thank you for taking my question. 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 cUHDRS, maybe the meeting minutes from the RMAT meeting at the end of 2024? Was that officially documented in what they send to you? Maybe how much detail do they go into in these meeting minute documents around the definition of the statistical analysis plan and the external comparator? Thank you.

Matt Kapusta (CEO)

Yes. Joe, I can confirm that in our November 2024 multidisciplinary meeting with the FDA and the written comments that we received, the FDA stated that the data from the phase I-II study in comparison to an external control may serve as the primary basis of a BLA submission. They also confirmed that the composite UHDRS would be considered an acceptable intermediate clinical endpoint to support accelerated approval. In that particular meeting, they did not get into specifics on the statistical analysis plan but had recommended that we pre-specify a stats plan. That was discussed in detail as well as the natural history protocol in our April 2025 meeting with the FDA.

Operator (participant)

Our next question comes from Luca Issi from RBC Capital Markets. Please go ahead. Your line is open.

Luca Issi (Senior Biotechnology Analyst)

Oh, great. Yeah. Thanks so much for taking the question. Maybe Matt, again, I appreciate the situation is still fluid here. 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 continuing to fight this versus just give up? Any call there? Much appreciated.

Matt Kapusta (CEO)

Yeah. I wouldn't characterize this as a fight. I think that we are 100% committed to continuing to collaborate and partner with the FDA to determine an expedited path to submit a BLA. I think we strongly believe that AMT-130 can meaningfully benefit patients.

I think we feel that we have what is considered to be the most compelling dataset in the field of Huntington's with three years of clinical outcomes data showing a meaningful slowing of disease progression. We think that if there are concerns or issues, that they ought to be addressed in a proper review. We will continue to work with the FDA to address any concerns they have with the hope of having an expeditious submission of a BLA in the near future. That is the pathway that we're going to be focused on. We are committed. We believe we have a drug that works. We have a patient group that has an urgent need. We're committed to doing everything we can to bring this to them as quickly as possible.

Operator (participant)

Our next question comes from Yanan Zhu from Wells Fargo. Please go ahead. Your line is open.

Yanan Zhu (Senior Equity Analyst)

Great. Thanks for taking our questions. Just first, a quick clarification. For the ALS program, is it intrathecal delivery? And if so, is the AE, the dorsal root ganglia AE, previously known to this route? Maybe just on the Huntington's program, just wondering, can you characterize how motivated or mobilized the patient and doctor community is on this issue and how that could help move the issue along? Thank you.

Matt Kapusta (CEO)

Okay. Walid, you want to answer the first one, and then I'll kick it to Kylie to do the second.

Walid Abi-Saab (CMO)

Thanks, Matt. Yeah. On the first question, the answer is yes to both. It is intrathecal delivery and it is dorsal root ganglia toxicity, which, again, as I said, unfortunately, is associated with this mode of administration. We knew this was a risk. Yes. Over to you, Kylie.

Kylie O’Keefe (Chief Customer and Strategy Officer)

Thanks, Walid. Yeah. As I just said, the patient and physician community are very motivated. They have a huge medical need and are collaboratively working together to look at how to move this forward. I think one of the things that's important is we received a big expression of hope and excitement coming out of the data. To have this disappointment a few weeks later is a bit of an emotional roller coaster for the community. I think they're working together to look forward and say, "How do we bring this therapy to patients?

Operator (participant)

Our next question comes from Patrick Trucchio from HC Wainwright. Please go ahead. Your line is open.

Arabella Ng (Biotechnology Equity Research Associate)

Hi. This is Arabella on for Patrick. I was just wondering if you could clarify if you've received any EMA or MHRA preliminary feedback on accepting the same dataset and external control for AMT-130 as primary evidence. Could you see XUS submissions proceeding ahead of FDA approval?

Matt Kapusta (CEO)

Walid, do you want to answer that?

Walid Abi-Saab (CMO)

Sure. We have not yet engaged in the U.K. or EMA or MHRA or EMA. That is the plan to go next to prioritizing the FDA. I will say that we are committed to work with the FDA also to continue to find a path forward and also with other regulatory agencies. We will advance as quickly as possible on all these fronts to bring this therapy to patients as quickly as possible.

Operator (participant)

For any additional questions, please press star followed by one. Our next question comes from Paul Matteis from Stifel. Please go ahead. Your line is open.

Paul Matteis (Head of Biotechnology Research)

Great. Thanks for fitting me in. As it relates to the meeting, again, answer whatever you're comfortable with. Given that your dialogue here, I guess, as I understand it, has been with a relatively similar group of people across 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 of a BLA, did you ask them why and what exactly had changed? Just separately, can you clarify for us what specific data have you shared with the FDA at this point? Have they seen more data from this three-year analysis than we have? Thank you so much.

Matt Kapusta (CEO)

Yeah. Paul, unfortunately, we're not going to be able to comment on the details of the specific meeting. We do hope for clarity once we do receive minutes. To the extent that there are material updates, we will endeavor to update investors and analysts. I think that's the answer to your first question. The second question. Oh, okay. Yeah. On the data, no, the data that was submitted to the FDA was consistent with the data that we shared publicly a number of weeks ago. Obviously, there's some additional data like sensitivity analyses that haven't been presented. There was no new follow-up or additional data that was provided to the agency.

Operator (participant)

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