uniQure N.V. (QURE) Earnings Call Transcript & Summary

Good morning, and thank you for standing by. My name is Jenny, and I will be your conference operator today. At this time, I would like to welcome everyone to the uniQure Phase I/II AMT-130 Huntington's disease Program Update. [Operator Instructions]. I would now like to turn the conference over to Chiara Russo, Senior Director of Investor Relations.

This morning, Unisenounced additional data on patients treated with our investigational gene therapy. ifezuntirgene inilparvovec or AMT-130 in our ongoing Phase I/II clinical trials in Huntington's disease, taking place in the U.S., EU and the U.K. This update consists of data on clinical endpoints and exploratory biomarker and safety and tolerability. Joining us for this investor event and webcast are Matthew Kapusta, our Chief Executive Officer; Dr. Walid Abi-Saab, our Chief Medical Officer; and to provide a clinician's perspective on the experience of patients with Huntington's disease. Dr. [ Vifor Song ], Professor of Neurology at the University of Alabama at Birmingham, UAB, Director of the UAB Huntington's Disease Clinic and a clinical investigator in this trial of AMT-130. Kylie O'Keefe, our Chief Commercial and Strategy Officer, will be joining us for the analyst Q&A at the end of this presentation. The slides included in this morning's webcast have been filed with the SEC and will be available on the Events and Presentations page of uniQure's website shortly after the conclusion of this webcast. 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 webcast. 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 quarterly report on Form 10-Q, filed on July 29, 2026 and other security filings. Given these risks, we 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 I am pleased to introduce Matthew Kapusta, uniQure's CEO.

Thanks, Chiara, and good morning, everyone. Thank you for joining us on today's call. This morning, we announced additional data from our ongoing study of AMT-130 in Huntington's disease. These results continue to provide evidence of long-term meaningful slowing of disease progression and support the primary analysis underpinning the license applications we submitted to the FDA and MHRA. . To date, no other program in Huntington's disease has demonstrated long-term disease modification after a single administration. AMT-130 does. As pioneers in this space, we are blazing a new trail in [ HD ], learning and deepening our understanding with every data point we generate. And at 48 months, we continue to see meaningful treatment effects. Huntington's disease is relentless and progressive there is nothing available today that changes its course. Our aim now is to bring forward the first disease-modifying treatment for people living with Huntington. The data we announced this morning include analyses at two time points. The first is a 48-month analysis based on the first 12 high-dose patients that have reached this time point. The second is a 36-month analysis reflecting all 15 patients, including 3 additional patients who have reached that time point since last year's update. Starting with the 48-month data, we continue to see treatment benefit across both cUHDRS and total functional capacity or TFC, with particularly significant effect on TFC demonstrating a 61% slowing of disease progression and stable treatment benefit at 48 months. TFC is the most direct measure we have of what patients and families care about. It captures whether someone can hold a job, manage their own finances and perform the daily [ tasks ] that allow them to live independently. It is also the agreed upon primary endpoint of our confirmatory study. While the primary [ cUHDRS ] analysis did not reach statistical significance in 48 months, we believe the trends are positive and meaningful for [ HD ] patients. [ HD ] patient lives are defined by moments in a year of meaningful moments is something no patient should have to give up. There is also an important limitation in the new updated external control. 53% of the external control data is missing at 48 months. While [ nice ] is inherent to long-term natural history data set, the patients who left the control were declining markedly faster than those who remained. So over time, the comparator increasingly reflected a healthier population than at baseline. This bias cuts against AMT-130, not for it. It understates treatment benefit and make statistical comparisons at the 40-month time point more difficult. As we advance as leaders in [ HD ], we will continue our collaboration with key stakeholders to assess the most meaningful way to evaluate long-term treatment benefit. When comparing to cUHDRS at 48 months across doses, we do see clear dose dependency, with the high dose showing a 1 point favorable effect on cUHDRS compared to the low dose. Importantly, this is an internal comparison that does not depend on the control and is what you would expect to see if there was a genuine treatment effect. Turning to the updated 36-month data. This is an important from a regulatory perspective as is consistent with the BLA primary analysis in our planned confirmatory study. Including the 3 additional patients, the 36-month data demonstrated an even stronger treatment effect. We now see 80% slowing of disease progression on cUHDRS, 67% slowing on TFC and favorable trends across all other clinical subdomains. As a reminder, the 3 additional patients at 36 months are not included in the 48-month analysis. In summary, we strongly believe AMT-130 has the potential to deliver meaningful long-term benefit to people living with Huntington, and we will continue to work tirelessly to deliver this treatment option to them. Patients and loved ones have waited long enough for a therapy that changes what this disease does to them. We firmly believe AMT-130 is that treatment. As we move forward, we remain laser focused in the near term on three areas: first, continuing to degree with the FDA and MHRA as their reviews advance; second, timely execution of our confirmatory study targeting initiation of patient screening before the end of this year; and third, advancing our commercial preparations so that we are ready to deliver this therapy if and when approved. With that, let me hand it over to Walid to walk you through the data in more detail. Walid?

Thank you, [ Mac ]. Good morning, everyone. Before I go over to the updated analysis, let me set the stage by reviewing the 36-month analysis from last year. This is the study design and statistical analysis plan supporting our recent regulatory submissions to the FDA and MHRA. Our primary endpoint is the compounded unified Huntington's disease rating scale or cUHDRS. We compare a change from baseline at 36 months against an external naturality cohort enrolled ACA using a [ property ] score methodology. At the time of [ last ] years analysis, which we presented to you in September 2025. 12 patients on the high dose has reached 36 months of follow-up as of the data cutoff of June 30, 2025. The main takeaway from this analysis was that AMT-130 high dose showed a statistically significant slowing of disease progression at 36 months. 75% slowing on [ cUHDRS ] and 60% slowing on total functional capacity or TFC. I draw your attention to the decline of the matched naturalist [ recover ] after 3 years. This corresponded to an average decline of 0.5 point per year on [ cUHDRS ] and 0.3 points per year on TFC. I will come back to these numbers later in my presentation. Today, we're updating you with the results of the analysis based on the data from the June 30, 2026 study data cutoff. 12 patients have now reached 48 months on the high dose and 12 patients have reached 40 months on the low dose. In addition, 3 more patients have reached 36 months on the high dose, making the 36-month time point fully representative of all enrolled patients at the high dose factoring in the 2 patients who dropped out at 12 and 15 months. There is an important comparator update that I would like to explain to assist in understanding the interpretation of both the 36 months and the 48 months data. The 48-month protocol and statistical analysis plan, which we submitted earlier this year, respecify the lowest current enrolled [ HD ] data set released in September 2025, We'll refer to this as [ enroll B ] throughout this presentation. Last year's 36-month analysis used the January 2023 release data set, which we'll call [ Andro ]. And on [ HDV ] contains everything [ in a roll HCA ] plus more than 2.5 years of additional follow-up on those same participants and 6,000 additional ones. It is the largest and most contemporaneous longitudinal natural history database available. It also overlaps in time with recruitment and follow-up of high-dose Cohort 2 in our Phase I/II studies. The [ Siphraneous ] controls are an FDA preference, and that was a significant factor in the choice. Our primary analysis follows the same plan as a 36-month analysis in 2025 that supported the BLA public. The primary endpoint compares the change from baseline in [ CVS ] at 28 months in the high dose against a propensity score mass control group from enrolled HCB. TFC is a key secondary endpoint. This slide shows the high dose in orange and the low dose in purple across all patients. The panel on the left shows all available data. The panel on the right show data from the 12 patients at the high dose and the 12 patients at the low dose for whom we have results up to 48 months. Since last year's update, these 24 patients accrued data from month 36 to month 48. There are several key observations worth noting on this slide. First, there is a softening of approximately 0.5 point between month 36 and month 48 on the high dose. Two components of the HRS drive this. [ SDMT ], which declined somewhat after month 36, perhaps a regression to the mean following relative stability between month 34 and 36; and TMS, which was noisy, with a few patients showing very large swings between month 36 and month 42. Second, we see those defendants across 4 years, adjusting a [ chain ] effect. This observation matters because it does not rely on a mass external control. The high dose, which is 10x higher than the low dose shows evidence suggestive of disease slowing when compared to the low dose. Third is, after 4 years, the low dose, which can be considered as some placebo, meaning it's expected to produce a lower therapeutic effect and could serve as an internal reference; shows a decline of approximately 2 points of cUHDRS. That is in line with the 0.5 point decline per year in the [ Maccenecontrol ] in the 2- and 3-year analysis reported over the last 2 years Okay. The results at 48 months are still missing the 3 patients who have not yet reached the 48-month mark in the study and at month 36 showed a slower rate of decline than the 12 patients who reached that time point a year earlier. As noted, our primary analysis uses enroll [ HDD ]. On the left panel, that analysis shows a 44% slowing of disease progression on cUHDRS with AMT-130 high dose compared to the match controls, not statistically significant at [ P 0.144 ]. It is noteworthy that the decline of the match controls at month 48 is 1.6 points which is only slightly more than the 1.5 points at month 36 that we reported last year using the matched control from enrolled [ HTA ]. I will address this topic later in my presentation. On the right panel, we show the results with TFC. TFC is a key functional endpoint. It is the most direct measure available of what patients and families care about. It captures whether someone can hold a job, manage their own finances and live independently. TFC is also favored by regulators and the primary endpoint for our confirmatory study. In this primary analysis, TFC shows 61% slowing compared to the [ Matrix ] under control with a nominal p-value of 0.008. Similar to cUHDRS, the decline in the match controls from enrolled [ HDB ] is lower at 0.94 points at 48 months on TFC compared to 0.88 points at 36 months and last year's analysis using enrolled [ HDA ]. These graphs show the time course for both endpoints. Again, I'll point out that the 48-month data do not reflect the complete high-dose data set as the 3 additional patients included in 36-month data has not yet reached this time point. Both cUHDRS and TFC show continued treatment effect through 48 months. These are the results for the other [ cUHDRS ] components. All show favorable trends relative to external controls. The [ true ] test remains strongly positive with significant nominal P values. As mentioned previously, [ GT ] showed some softening between month 36 and 48 and [ Otomoto ] score is relatively noisy. Let us take a closer look at the enrolled [ HDB Mass ] controls. Participants with longer follow-up tend to decline more slowly, which enrich natural history comparators, with slower progressors over time, a known phenomenon in [ naturals ] studies in many different rare diseases. The graph on the left clearly illustrates this point in the cohort of participants [ matin ] 30 highdose. Participants with last data point was at year 1, declined 0.91 points per year on cUHDRS. Those remain 3 years or beyond, declined by 0.41 point per year, less than half the rate. And the effect compiles over time, with each additional year of follow-up selecting for slower progressors. [indiscernible] roll HDB was also greater than enroll [ HTA ] exceeding 50% at year 4, which we believe further accentuate survivor bias in the data set. The graph on the right shows the consequence. Enroll [ HDD ] declined 20% less than enrolled HTA at 48 months. Notably, enrolled HCV begins flattening after year 2 inconsistent with men disease biology, while enrolled HTA continues a linear decline consistent with expectations for [indiscernible] atients. We believe these factors understate disease progression and tester control and therefore, the treatment effect of AMT-130 and that this bias compiles with longer follow-up. Given our observations on Enroll HDB's underestimation of disease progression, we conducted a post hoc analysis using Enroll HDA, the data set used in our regulatory submissions to the FDA and MHRA. On the left, this graph shows 54% slowing at 48 months in cUHDRS, nominally significant with the p-value of 0.041. I draw your attention to the fact that in this analysis, the level of missingness is lower than enrolled HTV as more than half the patients matched at baseline remained in the study at 2 months. In addition, the decline in cUHDRS at month 48 and the control group is 1.94 points, which is closer to 0.5 point per year we have reported in the prior analysis. On the right, we show the results for TFC with a 68% slowing and a nominal p-value of less than 0.001. The data appears to be robust. Patients who received the AMT-130 high dose showed very little decline 4 years after dosing on this measure of real-world functional abilities. For many of these patients, that means preserving a greater degree of independence, the ability to work and to care for 1 cell, which is highly clinically full. This slide shows the time course over the 48 months compared to the match controls from the enrolled HTA and the dashed gray line from the post-hoc analysis. The solid gray line shows the match controls from the primary analysis for reference. Let's turn to the results at 36 months. the time points used for our primary DNA submission and pre-agreed with the FDA for the confirmatory trial. These are the data we shared last year, the original 12 high-dose patients through 36 months shown in the orange dotted line. Adding the 3 additional patients who have since reached 36 months shown in the solid orders line, we see they're progressing more slowly than the original 12. They will be affecting the mean change from baseline for both cUHDRS and TFC. The gray line is the matched natural site control from enrolled HDD as prespecified in the primary analysis. These are results at month 36 from the primary analyses. AMT-130 high dose showed a robust 80% reduction in cUHDRS decline and a 67% reduction in TFC decline with nominal p-values of 0.005 and 0.011 respectively. Now that the analysis includes every patient who received the high dose in the study, we believe these data further strengthened the September 2025 analysis that form the basis of our regulatory submission. Across the other components of the cUHDRS, AMT-130 high dose showed favorable results ranging from 59% slowing on total [ motor ] score to over 120% slowing on the 2 cognitive endpoints as [ DMT and through ], both with nominally significant p-values. Turning to neurofilament light chain or NFL. From months '18 onwards, both doses trend near baseline. At the 48-month cutoff, mean change from baseline in CSF NFL was 4% above baseline on high dose and 8% below baseline on low dose. For context, healthy subjects aged 40 to 60 matching our population typically show a 1% to 3% annual NFL increase. while untreated early manifest HD patients show a 10% to 15% annual increase. Therefore, we believe the baseline NFL levels after 4 years are well below what would be expected as an effective treatment. Let's look at safety next. AMT-130 was generally well tolerated. The most common adverse events related to the administration procedure, all of which resolved. Since September 2025, there have been no new treatment-related serious adverse events in cohort 1 and 2 at either the low or high dose. As previously disclosed, since our September 2025 update, there was 1 treatment-related serious adverse event in Cohort 4, the lower volume cohort. CNS inflammation in on high-dose patient fully resolved with a short course of corticosteroids. There was also 1 suicide in a low-dose patient, approximately 5 years post-treatment, assessed as unrelated to therapy. Unfortunately, people with Huntington's disease experience a 9x higher risk of suicide [indiscernible] population, making it 1 of the [indiscernible] leading causes of death. This table provides the full adverse event data supporting the summary on the prior slide. In summary, AMT-130 continues to demonstrate meaningful slowing of disease progression. With all patients have reached 36 months, we again see a substantial treatment effect refarming the basis of our BLA submission. The 48-month analysis shows continued evidence of meaningful slowing of disease progression as measured by both TFC and cUHDRS. The dose dependence observed between the low -- high dose across 48 months supports evidence of biological activity. We believe survivor bias and missingness and the updated external control likely understates both disease progression in this population and the treatment effect observed with the AMT-130 at 4 years. Overall, AMT-130 continues to be generally well tolerated. To conclude, we believe that there is clear evidence that AMT-130 has the potential to slow disease progression and provide people living with Hunting's disease, the opportunity to maintain a higher quality of life for longer, which is incredibly meaningful to this community who have no approved disease-modifying treatment options. Before I turn over this presentation to Dr. [ Fong ], I want to say that these data will be presented at a future scientific meeting. We continue to make progress towards bringing this potential therapy to patients. We have submitted the BLA to the FDA and expect acceptance in the fourth quarter. We also submitted the MAA to the MHRA, which has since validated the submission. We are committed to Italian execution of the confirmatory study. Preparations are on target. We expect the first patient to be screened before year-end. We'll also be readvancing commercial preparations and look forward to providing more color on loss strategy early next year. With that, let me turn it over to Dr. [ Strong ], who will provide his take on these results. Victor?

Thank you, Walid, and good morning, everyone. I'm Dr. [ Victor Son ], Director of the Huntington's Disease Clinic at the University of Alabama at Birmingham. And I'm pleased to be here today to provide a clinical perspective on this additional data for AMT-130. My comments are based on my own clinical expertise and experience with AMT-130 as a site investigator on this study. Since the [ HT Gene ] was first sequence over 30 years ago, we have been on a quest to find a therapy that can slow the progression of the disease. But today, there is still nothing. There are currently no FDA-approved therapies to slow the progression of Huntington's disease, the biology is one of inevitable progressive decline. With that backdrop, the data from the AMT-130 program remain encouraging to me. On their own, they provide stronger evidence of a clinically meaningful effect over 4 years. a trend that continues to point in the same direction on both cUHDRS and TFC, 4 years after a single administration is a pattern that I want to keep watching closely. But my impression is that the totality of the data point toward a meaningful treatment. I think it would be helpful to underscore at least two factors in my evaluation of the data. First, I think it is worth revisiting and emphasizing that the 3-year point remains the time point that is the grounding for the BLA and confirmatory study for a reason. Three years is long enough to see a measurable difference in disease progression, but short enough to align with an individual patient's research participation window. I certainly welcome uniQure's production of longer-term data to provide additional context but it is not necessarily the case that longer-term data are more indicative of benefits than 3-year data. Second, as a clinician working with patients with this disease, I think of the data in terms of its real-world significance. When I look at an external control that appears to decline more slowly in patients with longer follow-up, that would be contrary to my impression and knowledge of how the disease typically progresses. It is also contrary to how I see my patients progress in their disease. This speaks to why TFC matters clinically. And in my assessment of the data at 36 and 48 months, it isn't just another statistical score. It tracks whether a patient can still hold employment, manage finances, perform tours and care for themselves. In the real world as opposed to statistics patients can either do these things or they cannot. The sustained treatment difference on that measure through 4 years suggests to me that the treatment effect may be translating into real functional capacity for these patients despite a less than conclusive primary analysis. I'm also encouraged that the confirmatory study will be grounded in measure that relies on real-world function as an assessment. A deeper look at the data and an eventual full panel at 48 months may help understand the longitudinal clinical profile a bit better. but it is relatively clear to me that if the performance presented today were reproduced in the wider patient population that would still constitute a meaningful improvement for patients and their families. We will slow this disease before we stop it. And on balance, I believe this data represents a meaningful step toward doing exactly that, and I'm happy to reflect on it with you today. And now I'll pass it back to CEO, Matthew Kapusta, to lead the Q& A.

Thank you very much, Dr. [ Sun ]. With that, operator, we're ready to open the call to Q&A. .

[Operator Instructions] And your first question comes from the line of Morris Ryder with Guggenheim Securities.

This is [ Marion for Debjit ]. So assuming AMT-130 does receive accelerated approval perhaps for both the UniCare team and for Dr. [ Sun ], what do you think will be the impact of this 4-year data on AMT-130 ability to gain market share? And maybe just one quick follow-up, could you just clarify which data at this point has actually been submitted to the FDA and MHRA? Is it just the unequal 12 patients? And is it compared to [ rural ] HD A or B?

Yes. It's Matthew Kapusta. Thanks for the question. Let me take the second question first. So the data that's been provided in the BLA submission is the data that we presented last year. That was the data that was agreed to with the FDA, that could be the primary basis of the BLA submission. And that data incorporates 12 patients at the high dose, and it's compared against Enroll [ HDA], which was the enrolled HD data cut that we presented last year. For the second question, I'll pass it over to Kylie.

Thank you very much for the question. I think one of the things that's important is we remain highly confident in the ability of AMT-130 to meaningfully slow disease progression, which is a profound importance to [ HD ] patients who currently have no disease-modifying treatments. . As Dr. [ Sung ] said today, we think the 3-year time point is incredibly important because it balances the ability to show meaningful slowing of disease and also balances the natural history components as well as the elements of research participation for patients. So we think this is -- this 4-year data is additional longer data that helps demonstrate that meaningful slowing of disease.

Yes. And I just want to add -- I want to add one thing. I mean, when you step back and you look at 4 years after a single administration, these patients haven't even lost a full point in cUHDRS, they haven't even lost 4 points in total functional capacity. This is clinically meaningful for patients. And I think with the additional follow-up data we believe that this is -- there's a significant unmet need here that needs to be filled. Dr. [ Sung ], do you want to add any comments?

Yes. I mean my main comments like you were alluding to, Matt, is just that in a setting where we have no approved therapies that can slow the progression of the disease the 48-month data still offers that we are still slowing the clinical progression of the disease. And from the perspective of my patients that are that have been treated and are in the study, they're still holding very stable. So I think that's kind of the lens that I look at at all, is we don't have anything else that can slow the progression, and this is still doing that at 4 years, which is still significant.

Your next question comes from the line of Joe Schwartz with Leerink Partners.

Thanks very much. It's pretty striking how TFC holds up better than cUHDRS even against the updated control data set, which is plagued by survival by us. Why do you think that is? And then what led to using the updated enrolled [ HD ] cut? Was this an FDA request or your own choice do you think the FDA will rerun the 36-month analysis and -- with the updated data set? And do you think that, that could constitute a major amendment?

All right. So this is Walid. I'll take the questions or a bunch of them. So look, TFC is the endpoint that matters most to patients, to clinicians and also to regulators. It measures function. And any decline there actually has immediate consequences to people's quality of life, whether they're able to hold a full-time job or take care of themselves. And that's why it tends to be much more relevant. It's very impressive that after 4 years, as Matt indicated, we -- the 12 patients that reached that time point only does 0.3 points. cUHDRS tends to be a little bit more sensitive. It picks up on some of the cognitive endpoints and the motor scores we've had some noise in the motor score. And the cognitive tests sometimes show variability and performance could change based on what's happening on that given day. Whereas TFC is better -- it gives you a much better sense of what's going on overall with the patient. So I think it reflects more how they're doing in general. And I think that's what we're seeing here. In terms of [ flight ] we use the new cutoff enroll HD, well, [ Enroll HD ] is an ongoing study. CHDI releases data updates as over time, every few years. And they released a data update in September 2025, which was between the last time, we did the analysis on the 3 years. At that time, we used the most updated enrolled [ HD ] data cut. And now it was time for us to evaluate the 4-year data. we did what was the right thing, which is to use the most recent enrolled [ HD ] data cut that provides 2.5 more years of follow-up on the existing patients and 6,000 more participants has more contemporaneity compared to our study, and that's really what regulators usually look for. It's difficult for me to speculate what will FDA do, whether they will rerun the analysis with the new data cut or not, that is something that we will deal with if the FDA assets to run it or if they are in themselves.

Yes. I mean, I will add that we have rerun the 36-month analysis with [ Enroll HDB], and the results continue to be very meaningful. The divergence between enrolled HDA and B, really become more striking at 48 months. They're starting to diverge it 36 months, but it's more modest. And so the impact on that analysis, even if it is rerun, is not incredibly meaningful. .

I noticed there was also a question about major amendments. If we add the data, it's really very difficult for us to speculate. If the FDA asked for the data, we definitely will provide it. and it's at their discretion whether they believe this is a major amendment or not.

Your next question comes from the line of Paul Matteis with Stifel.

In the past, you've commented in RollHD patients at some of the earlier time points like 2 and 3 years performed fairly similarly on these endpoints as compared to some of the other Huntington's disease natural history studies. Is that still the case with Enroll HDB? And is that still kind of the case at 4 years? Sort of, I guess, taking a step back, I mean, I guess the reason why I ask is I think many of us are trying to think about what are some of the sensitivity analyses FDA might do. So one logical one would be to kind of look at other natural history cohorts that are out there and available. So maybe that's one piece. And then really just on that other side of that, like what other sensitivity analysis here do you think might be relevant stress test of the data that the agency could do? And how many of these have you done yourself?

Well, thanks, Paul. First, on [indiscernible] HD, and I think I mentioned this a little bit in my presentation. We have started sharing external -- comparison to excel control, starting with the 2-year time point, if you recall, at that point, we compare it to track and predict. And at that point, again, it was equivalent to the match controls are declining by 0.5 point on cUHDRS and 0.3 point of TFC. Last year, when we updated on the 3-year analysis, just because over time, there's not enough patients in track and predict to be able to be matched at the 3 years. They suffer from significant level of [indiscernible] -- we switch to nalHD, which is more robust., And again, it showed that at 3 years and actually throughout the year 1, 2 and 3, 0.5 point of cUHDRS and 1/3 of a point on TFC. This is the first time that we see with enrolled HDD. And as we showed in the presentation, there's a break between starting to see a Tier 2, very evident by year 4, where you see a significant break from this linear progression, In the end, averaging about 0.4 points on cUHDRS, which is 20% lower. So we do think that the data overall support the previous analysis., And the other piece that I want to say is that if you look at our internal control itself on the low dose, even if you assume that there's no efficacy whatsoever on that dose, they also declined about 0.5 point on cUHDRS. So I do think that the overall analysis do support the fact that beyond 3 years, enrolled B is really suffering from this survivor buyers and underestimating the decline in the natural history cohort. In terms of sensitivity, we've run a number of sensitivity analyses ounces, more than 10 approximately, which were prespecified and included in the SAP. And across all of those, across the majority of those, I should say, we have better percent slowing of disease progression, a higher level of decline under control, getting closer to that 2.0 that we talked about, And we reached statistical significance and more than half of those. In fact, the primary announcement that we shared with you was the more conservative of the group. So I think that kind of answers your question.

Your next question comes from the line of Joseph Thome with TD.

Maybe just the first one, can you talk a little bit about the consistency of response in the high-dose patients? I think Dr. [ Sam ] mentioned that overall, his patients seem to be relatively stable. So is a decline between year 3 and year 4 driven by a few patients? Or any context around that? And then maybe for Dr. [ Song ], if you could just talk a little bit about if this is approved, maybe what proportion of your patients you think would be good candidates for therapy kind of like within the first year or so of launch?

Thanks, Joe. Yes, the data overall are very consistent. There's little changes from an outlier. Maybe 1 exception on cUHDRS, which is driven by that [ TMS ] that I mentioned. There was some noise in the data, and there was 1 particular individual that probably was pulling the average down significantly compared to last year. We're following this with the site. But overall, if you look across the remaining patients, they're all showing [indiscernible] results and particularly TFC, they're all continuing to progress or not progress actually the case it is between years 3 and year 4. And I'll turn it over to Dr. [ San ] for the second question.