Good day, ladies and gentlemen, and thank you for standing by. Welcome to the regulatory update on AMT-130 for Huntington's disease. At this time, all participants are in a listen-only mode. After the speakers' opening remarks, there will be a Q&A session. To ask a question at that time, you will need to press star 11 on your telephone keypad. At this time, I would like to turn the conference over to Chiara Russo, Senior Director of Investor Relations. Ms. Russo, please begin.
Thank you. Good morning, and thank you for joining us. This morning, uniQure announced alignment with the Food and Drug Administration on key elements of the accelerated approval pathway for our investigational gene therapy AMT- 130 for the treatment of Huntington's disease. On this call, we will walk through the key elements we have reached alignment on with the agency, as well as our anticipated next steps. Joining me for this webcast are Matt Kapusta, our Chief Executive Officer, and Dr. Walid Abi-Saab, our Chief Medical Officer. Please know that we will be making forward-looking statements during this investor call. All statements, other than statements of historical facts, are forward-looking statements. They are based on management's beliefs and assumptions and on information available to management only as of the day of this conference call.
Our 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.
Thank you, Chiara, and good morning, everyone. We're truly thrilled today to announce that following our Type B Meeting with the FDA in late November, we have reached alignment on key elements of an Accelerated Approval pathway for AMT-130, our wholly-owned investigational gene therapy for the treatment of Huntington's disease. This milestone represents a significant step forward for the Huntington's disease community and an incredible achievement for uniQure. The FDA's feedback, which was based on a thorough review of our most recent clinical data and discussions with our medical team, underscores the potential for AMT-130 to address unmet medical needs for the treatment of Huntington's disease. We're very grateful for the agency's guidance and commitment toward helping those people who live with this debilitating disease.
The accelerated approval pathway avoids the need for an additional lengthy and costly pre-submission study, thereby reducing our time to potential licensure by approximately five years. We've already begun BLA readiness activities, including accelerating our CMC preparations, and very much welcome the opportunity to bring this potentially transformative treatment to patients as quickly as possible. With approximately 70,000 people diagnosed in the U.S. and Europe and hundreds of thousands more at risk of inheriting this devastating disease, Huntington's represents one of the world's largest genetically defined unmet needs. As such, AMT-130 has generated significant interest from patients, clinicians, investors, and strategic parties alike.
We're confident that our existing cash resources, alongside the significant cost reduction initiatives implemented earlier this year, provide the resources needed to swiftly advance AMT-130 to a BLA submission, and we look forward to providing more granularity on timelines and updated financial guidance in the new year. Now, I'd like to turn the call over to Dr. Walid Abi-Saab, who will provide more detail on the data presented, the regulatory path ahead, and next steps for the program. Walid?
Thank you, Matt. Good morning and good afternoon, everybody. As you can imagine, I'm extremely excited that we have reached alignment on an accelerated approval pathway with the FDA. This is excellent news for the Huntington's disease community, including investigators and advocates whose unwavering support have made this update possible. In fact, without the tremendous work that was done in this field for decades to further our understanding of the biology, as well as the clinical course of the disease and associated biomarkers, and most importantly, without the invaluable contributions, commitment, and generosity of people living with Huntington's disease and their loved ones, we would not be where we are today. So, to all of you, a deep, heartfelt thank you. First, I will share a regulatory update on our Huntington's disease program.
I'd like to briefly review the progress we've made this year with our ongoing phase I/II studies of AMT-130 and the data they have produced. In May of this year, AMT-130 became the first Huntington's disease investigational drug to receive Regenerative Medicine Advanced Therapy, or RMAT, designation, which allows for more frequent interactions and discussions with regulators. In applying for the designation, we submitted promising results that we shared with you last December, which included data from eight patients at 24-month follow-up compared to an external natural history control using propensity score matching. Those analyses provided preliminary clinical evidence that AMT-130 has the potential to address unmet medical needs for the treatment of Huntington's disease. Thus, the designation was granted.
In July, we expanded on this analysis with data from 21 patients at 24-month follow-up, demonstrating for the first time a statistically significant, dose-dependent, and potential durable slowing of disease progression based on cUHDRS compared to an external propensity score-weighted natural history control. Additionally, the data showed a statistically significant reduction from baseline in cerebrospinal fluid neurofilament light chain levels at 24 months, further supporting AMT-130's potential therapeutic effects. Building on this progress, the uniQure team prepared a comprehensive briefing book with both substantial non-clinical, CMC, and clinical data, as well as specific questions for an initial multidisciplinary Type B meeting with the FDA. Additional data from three high-dose patients having crossed the 24-month duration were also included with the updated data from July. So, in total, 24 subjects with two-year data, 12 on the high dose and 12 on the low dose, were submitted in the briefing book.
We went into the meeting looking for clarity on two important topics. One, that the potential therapeutic benefits of AMT-130 may be demonstrated relative to a natural history external control group in the ongoing phase I/II studies. And two, that data from the ongoing phase I/II studies may serve as the primary basis for an accelerated approval application of AMT-130. During this meeting, the FDA provided us with important guidance that allows us the opportunity to submit a BLA using the accelerated approval pathway for AMT-130. First, data from the ongoing phase I/II studies compared to a natural history external control may serve as the primary basis for a BLA application for accelerated approval. This means that an additional registration trial for accelerated approval will not be required. Second, the cUHDRS may be used as an intermediate clinical endpoint to support an accelerated approval application.
lLastly, reduction in CSF and NfL levels may serve as supportive evidence of therapeutic benefit. We are very pleased that the agency provided us with this important clarity on a path forward. In terms of next steps, we plan to engage with the FDA in the H1 of 2025 to finalize our statistical analysis plan and technical CMC requirements. In the meantime, enrollment in Cohort 3, which aims to evaluate the effects of immunosuppression on perioperative safety, is almost complete. We expect the last of the 12 patients to be dosed in the Q1 of 2025, at which time a total of 45 patients would have been dosed with AMT-130.
We expect to provide an initial safety update from Cohort 3 in the H1 of 2025 and remain on track to deliver a three-year update on 21 patients from Cohorts 1 and 2 in 2025, similar to the analysis shared in July. With that, I'll turn the call back over to Matt.
Thanks, Walid. As we close out 2024, uniQure stands on a markedly different value-creating trajectory compared to when we began this year. We now have a clear and accelerated path to potential approval for AMT-130 in Huntington's disease, avoiding the need for an additional pre-submission study and significantly expediting the registration of this potentially first and best-in-class therapy. Our decisive cost containment measures, combined with our strong financial position, position us to advance AMT-130 as aggressively as possible. At the same time, we've initiated three new clinical studies over the past six months, each of which provides additional opportunities to create value in 2025 and beyond. With that, we will open the call to take questions. Operator, please proceed.
Ladies and gentlemen, if you have a question or comment at this time, please press star 11 on your telephone keypad. If your question has been answered or you wish to remove yourself from the queue, simply press star 11 again. Again, if you have a question or comment at this time, please press star 11 on your telephone keypad. Please stand by while we compile the Q&A roster. Our first question or comment comes from the line of Salveen Richter from Goldman Sachs. Mr. Richter, your line is open.
Hi, it is Lydia on for Salveen. Thanks so much for taking our question. Just on the path forward, would you still consider exploring an external partnership now that you have an accelerated approval path? Thanks so much.
T hanks for the question. Right now, we are focused on driving AMT-130 to a BLA submission. That, we have the financial resources and made the significant decisions to reduce our burn rate earlier this year, that really put us in a position to be aggressive with moving this program forward. So our first order of business is taking AMT-130, advancing it, and that's really what we're focused on right now.
Got it. Thank you.
Thank you. Our next question or comment comes from the line of Debjit Chattopadhyay from Guggenheim. Sir, your line is now open.
Hey, good morning and congrats on the update here. Matt, I just wanted to confirm one thing. The filing is on the two-year data, and the FDA does not require the three-year follow-up for the submission. And if the FDA does require the three-year follow-up, is there a threshold on the cUHDRS that the agency wants to see?
Debjit, there was something wrong with the audio. Can you just repeat that?
So just wondering if the filing is gated only on the two-year data, and you wouldn't need the three-year follow-up data for the submission. And if you need the three-year data, does the FDA have any threshold on the cUHDRS?
T hanks, Debjit, for the question. So two things on this. One is keep in mind that just given the cadence of enrollment, right, we already have patients at this point in time. We're going to have a bolus of patients that have three years of follow-up. In fact, next year, I agreed it. The other thing that I would mention is that we expect to have discussions specifically about the statistical analysis plan, which will be pre-specified in the H1 of next year. So we expect to provide some additional guidance in that regard early in the new year.
Thank you.
Thank you. Our next question or comment comes from the line of Paul Matteis from Stifel. Mr. Matteis, your line is open.
This is James on for Paul Matteis. Thanks for taking our question. And I actually had a follow-up there on kind of the timelines here. I guess, is there going to be a kind of set timeline, you think, in terms of when this analysis will be done in the sense of everyone will be at three years, or is it going to be kind of a mix just given where patients are? And then kind of two, on that kind of designing an SAP, just kind of curious what sort of effect size you think you're powered for, I guess, in a sense, in terms of showing statistical significance. And in the two-year cut, we saw a very large implied kind of effect size versus natural history. So kind of just curious how that informs what the SAP may ultimately look like. Thanks so much and congrats.
Sorry, Paul. Could you repeat that question?
This is James on for Paul. Can you hear me?
Ladies and gentlemen, please stand by.
I think so.
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Hello?
Can you hear me?
We can hear you better now.
Okay. Great. This is James on for Paul. Sorry, I think we've been having some audio issues. Just kind of wanted to have a quick follow-up on sort of that timeline question in the sense of, do you think everyone needs to be at three years? Is there kind of a set threshold in terms of when this analysis is going to be done, or is it kind of just a mix of where patients are kind of just at in terms of their follow-up? And then two, on the designing of the SAP, what sort of effect size do you think you are powered for in terms of showing statistical significance? Obviously, we saw statistical significance at two years. So just kind of curious what you think that how that informs kind of your designing of the SAP. Thanks so much.
Ladies and gentlemen, please stand by. Ms. Russo, your line, we cannot hear you. Ms. Russo, if you can hear my line, you may need to disconnect and reconnect.
No.
Okay. We can hear you now. It's cutting in and out. Ladies and gentlemen, please stand by.
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The PIN you entered is not valid. Please enter your dial-in PIN and press pound.
I think so.
Okay. You're connected. Can you hear us?
Yes, we can hear you now.
Okay. You're back on.
Great. Sorry. Paul, you'll have to repeat your question.
No worries. This is James on for Paul. Thanks for taking our question and congrats on the alignment here. I did want to follow up on kind of that last question in terms of timelines in the sense of, is there a certain threshold or certain timeline that all patients need to get to in terms of doing this analysis? Could it be all three-year data? And then two, in terms of kind of designing the SAP, I'm just kind of curious what sort of effect size you think you're powered for in terms of showing a statistical significant benefit. Obviously, we saw in the two-year cut a stat-sig benefit and a pretty large implied effect size versus natural history. So just kind of curious how that informs how you're thinking about the SAP. Thanks so much.
So apologies, by the way. We just had a major internet crash, so we're back on at least. So just to answer those questions, at this juncture, there is no specific guidance that we've received in terms of a particular number of patients that have to reach a specific amount of follow-up. And we'll obviously provide more guidance as we have future discussions with the FDA. The second part of your question is, in the end, we demonstrated in our July data presentation that we had statistical significance even with 12 patients that had achieved two years of follow-up. So I think we feel really encouraged by the data that we have thus far and our ability to achieve a prospectively defined endpoint with the FDA.
Okay. Thanks.
Thank you. Our next question or comment comes from the line of Joe Schwartz from Leerink Partners. Mr. Schwartz, your line is now open.
Hi. Jenny on for Joe. Congrats on the progress, and thank you for sharing. Can you give us some more details on how you're accelerating your CMC activities, what still needs to be done, and how many doses do you think you'll be able to supply the market by the time the FDA completes the review? Thank you.
So I mean, the major things that have to be done, which are all standard, is to finalize the process validation and to do our PPQ consistency runs. We think we're going to be in a very good position. There's no tech transfer that's going to be required. The process that we're utilizing is highly comparable with the process that we used for Hemgenix, and the material is being made in a facility that is already licensed by the FDA to produce gene therapy. So we feel like we're going to be in a good position in that regard to complete our CMC activities. In terms of the readiness for commercial launch, just keep in mind this is not an IV-administered product, so the quantities that are actually administered are relatively small.
So we feel like we'll be in an excellent position to produce the material that we need for launch of the product.
Thank you.
Thank you. Our next question or comment comes from the line of Luca Issi from RBC Capital Markets. Your line is now open.
Oh, great. Thanks so much for taking my question. And obviously, congrats on your alignment with the FDA here. Maybe two quick ones. Maybe Walid, just kind of stepping back, can you just talk about endpoints here? I find it fascinating that you're talking about cUHDRS and NfL versus Wave is talking about imaging and PTC is talking about mutant huntingtin. Again, I appreciate these are different approaches. And obviously, there's some complexities around CBER versus CDER. What's the best way to rationalize why the FDA is asking different companies different endpoints there? So again, any color there'd be much appreciated. And then maybe Matt. Can you just talk about Europe? What is the next interaction with the EMA, and how should we think about the path for approval there? Thanks so much.
All right. Thanks, Luca. This is Walid. I'll take both questions, actually. On the first one, on the endpoints, I mean, I think it's very difficult to speculate. The FDA feedback is often given based on the questions that are asked, honestly, and it's very difficult to speculate how these discussions with other companies are turning out. We've always indicated that changes in, for example, mutant huntingtin is unlikely to serve a basis because simply there's a very large trial with tominersen that showed dose-dependent reductions. At the same time, patients did not get better. If anything, they got worse, unfortunately, in that trial. So what I can comment is on our discussions with the FDA, we made a case that cUHDRS is a likely endpoint to be able to predict potential for benefit, and as such, could serve as an intermediate clinical endpoint.
It is something that's been actually used often. There's a lot of new data now have accumulated to a great extent, also thanks to the tominersen data set that is very large. I think the agency is feeling comfortable with it to serve as an intermediate clinical endpoint, which is reasonably likely to predict the future potential benefit. On the NfL, I think it's also there's increasing evidence that NFL, although not specific for Huntington's disease, is very specific for neuronal injury and actually leaks out of the cells when they are injured or degenerating. For us to have data that we've shared with you previously that robustly show a reduction from baseline at two years when you would expect a significant increase from baseline as the disease progresses also serves as a very solid foundation for this. We're very happy.
We feel the FDA is actually reacting to data that we presented. This data is getting more and more mature, as Matt said. What we included in the briefing book are data from 24 subjects who have crossed the two-year time point, 12 on the low dose and 12 on the high dose. But again, at that time, we also had a number of subjects, particularly on the low dose, that have been for whom we have more data. On the EMA, the plan is to engage with the EMA with a series of meetings starting early in 2025. So our aim is to align with them on a path, which we hope would be very much in line with what the FDA is charting for us and agreeing for us on a way forward. So we'll keep you posted. Thank you.
Fantastic. Very clear. Thanks so much.
Thank you. Our next question or comment comes from the line of Eliana Merle from UBS. Ms. Merle, your line is open.
Hey, guys. Thanks for taking the question and congratulations on the update. Just want to clarify a little bit. What's your expectation for when you plan to file the BLA? Is it that you're waiting for the three-year data and the safety from cohort three, and then you could file towards the end of next year? Or just help us think through that. And then just a second question. In terms of the clinical endpoints, I guess, what does the FDA view as a clinically meaningful difference on cUHDRS? And I guess, should we interpret this as the FDA viewing your data reported as already showing a meaningful difference since they're reaching sort of alignment with you on that endpoint? Thanks.
Ellie, I guess I can take the first question, and Walid, you can take the second question. What I can tell you is, internally, we are going to be aggressively moving forward to put us in a position to submit a BLA as quickly as possible. We've had one meeting with the FDA, and it was an extremely productive meeting that we're very excited about. We expect to have some additional discussions with the FDA beginning in the Q1 of next year, and once we have those discussions, we'll provide more color on the specific timing of a BLA submission.
Thanks. And I'll take the second question. Again, I think it's also same color as what Matt said. This was the first meeting whose purpose was actually to have a high-level agreement with the FDA on the development plan across multiple disciplines. Now, in addition, we asked specific questions for which we got specific answers, as we shared in the PR and also in the call earlier today. There's not been any more detailed discussions. The question of clinically meaningful difference did not come up at all in our discussions. So that doesn't mean it's not what's on the table, but it didn't come up. And I think the purpose of the subsequent meetings, as Matt said, would be to nail down, from a clinical perspective, the statistical analysis plan, the protocol for the external cohorts, and how we're going to be comparing those.
But the meaningful clinical difference did not come up. And to me, I'm not necessarily worried about it. I think the agency has seen the initial data as supportive for a potential accelerated approval and engaged with us in a very constructive discussion to help us achieve their goal, which is also their goal to bring medicines to patients as quickly as possible in a safe way.
Great. Thanks. Congrats again.
Thank you. Our next question or comment comes from the line of Danielle Brill from Raymond James. Ms. Brill, your line is open.
Thank you. Good morning and congrats on the progress here. I guess I'm just curious why you can't pursue a traditional approval with cUHDRS versus natural history. What additional evidence does the agency want, or how much additional follow-up are they looking for to confirm benefits? And then as a follow-up, what are your expectations at this point for confirmatory trial requirements? Thank you.
Maybe I'll take a stab at that while leading. You can jump in. I think that the—I mean, just keep in mind the progress that's being made from a regulatory perspective. I think what we're excited is that the agency has recognized cUHDRS as an intermediate clinical endpoint. And this is not just in Huntington's disease, but I think the agency often takes a skeptical approach of composites because composites are a mixture of different variables. But there's been a tremendous amount of independent data that has shown that the composite cUHDRS is actually highly correlated with progression of disease and, if anything, more sensitive than some of its individual components. The FDA does seem to be focused on total functional capacity, which is a strong measure of the quality of life and the impact of the disease on patients.
So that's something that the agency perhaps may be looking at and thinking about full approval. But it's not clear. In all honesty, the requirements for full approval are still on the table. And even for what would constitute confirmatory evidence are still on the table and whether or not a new study would even be required. So those are things that we need to discuss further with the agency in the H1 of next year, and we'll provide input or feedback once we have those conversations.
Thank you. Our next question or comment comes from the line of Uy Ear from Mizuho. Mr. Ear, your line is now open.
Thanks. Thanks, guys. Congrats on the progress. So just a couple of quick questions. So you indicated in the press release that there were staff and senior staff members at the FDA meeting. Just maybe provide some colors on who was there and what was sort of your read of their impression on the data, the briefing books that you saw, and why is it, I guess I'm just going back to a little earlier where you kind of told us not to get too excited because of other companies, FDA more favorable to biomarkers. And essentially, you told us to not get too excited. Just wondering what was different in terms of your expectations going into it and coming out of this with these alignments.
Second question is, on CMC, can you remind us whether the current product, I guess, do you need to do anything? Was there a bridging study to get to commercial products? Thanks.
I mean, maybe again, I can chime in, and Walid, I think you should also discuss the kind of tenor or tone of the meeting. But I think that the. I'm not going to comment specifically on who attended the meeting. What I can tell you is that there were, I think, over 30 people. This was an in-person meeting, but also hybrid, of course, with people dialing in, but it was a multidisciplinary meeting with, I think, over 30 people that had attended, and there were senior FDA officials at the meeting, and that's obviously one of the benefits of being under RMAT designation. I think that obviously, everybody's interactions on different programs are all nuanced and different. We have a lot of insight into other companies going through this process and understand that it was a journey to achieve alignment with the FDA.
And so we were really pleasantly surprised while we believed in the adequacy of an accelerated approval pathway. We're really pleasantly surprised by our ability to align in the initial RMAT meeting. But honestly, we think this is a testament to the strength of our data and the long-term outcomes that we have. And the FDA, in my mind, leaning in to really try to work with sponsors to find expedited pathways of bringing these transformational therapies to patients. Just lastly, on the CMC piece, we do not require any material changes to the process that we use to make the material that is being utilized in our phase 1/2 study compared to what we expect would be utilized commercially.
We don't expect there to be any bridging studies that are required because of the fact that the process is going to be largely consistent with what we have used in our clinical testing.
Thank you. Our next question or comment comes from Sami Corwin from William Blair. Your line is now open.
Hi there. Congrats on the alignment, and thank you for taking my questions. I guess I was curious as you're kind of thinking in the future about labeling what the included population might look like given the requirement for cUHDRS stage and disease severity in the trial and if you think you'll need to conduct additional studies in the future in order to expand this? And then I was wondering if you could also remind us how many centers or doctors are currently equipped to do this surgical procedure in the U.S.? Thank you.
Thanks, Sami. Just Walid. So I think this is really premature. There's been no specific discussion talking about labeling and indication. But very simply, we set out to test the hypothesis that blocking a mutant huntington protein, lowering it, and particularly lowering the HTT, which is now becoming more and more clear that this plays an important role, is a way to be able to change the course of the disease. And I think now we're starting to generate data to show that, and that's why we are where we are today. So I think we will be discussing with the FDA what this study that we have would allow us in terms of label.
But I would imagine if this is a therapy that will affect the fundamental underlying biology of the disease, I think there will be a lot of collaboration with the agency to see how best to make it available to the most appropriate patients and what additional work potentially could be done to enlarge this to even an earlier stage of the disease. So in terms of these centers, I think currently we have a number of centers in the U.S. and some in the U.K. But we are, of course, as part of our preparation for the future, would be planning to increase those. I mean, this would not be very different than any of the highly sophisticated type of therapies that you will get at very specific centers who are equipped to do these types of surgeries, equipped also with MRI-guided technology to be able to do this.
As a one-time therapy, I think that will be also compatible with administering the therapy going forward. But again, we are in the early stages of this. We're all hands on deck preparing for this. And we will be providing more comments as we further articulate that story.
Great. Thank you. Congrats again.
Thank you.
Thank you. Our next question or comment comes from the line of Peyton Bohnsack from TD Cowen. Mr. Bohnsack, your line is open.
Hey, good morning, guys. This is Peyton on for Joe. First off, congratulations on appearing to be a very productive meeting. I guess looking forward to the safety data from Cohort 3, would you need to have that before you would submit? And if you saw benefit from the perioperative immunosuppression, how would you incorporate that overall into the BLA submission? Thanks.
What I would say is we believe, based on data from the phase 1/2 study, in particular, the first two cohorts, that both doses are generally safe and well tolerated with a manageable safety profile. So that's even with the initial immunosuppression regimen that we had. I think we view that the third cohort is really in order to optimize the immunosuppression, and we don't necessarily view it as a long pole in the tent or a prerequisite.
Great. Thank you.
Thank you. Our next question or comment comes from the line of Kristen Kluska from Cantor Fitzgerald. Ms. Kluska, your line is now open.
Hi, good morning, everybody, and congrats on these updates. So originally, you had guided to the street that it may take a few discussions to get some concrete feedback on the path forward. But it appears with today's update that one meeting alone gave you a really good sense. So I was hoping you can maybe speak on anything from a macro perspective that may have changed this. I know the FDA has been heavily involved in this. They recently attended an event hosted by HDSA. So curious if that or just anything from a macro perspective gave them the ability to give you more concrete feedback on this first meeting versus a series of them.
No. I mean, I think I know what you mean when you talk about macro, and did that create some kind of urgency, the political landscape? Honestly, we just don't buy that. We don't see that. We think that this is not. The FDA is not acting as a political animal. The FDA is focused on data and focused on executing their mission, and if anything, our view is that the speed of which that we've been able to align with them is really more of a testament to the substantial amount of data and follow-up, including clinical outcomes that we've been able to demonstrate and not something unrelated or macro or political in nature.
Thank you. Our next question or comment comes from the line of Yanan Zhu from Wells Fargo Securities. Ms. Zhu, your line is open.
Great. Thanks so much for taking our questions and congrats on the alignment. Three questions, if we may. So first, on the safety database for the original surgical procedure and route, is there a sense of the size of safety database required for the filing? And could that be more gating than the efficacy cohort size? And second question on the size of the natural history control or the leeway of selecting those natural history patients. Do you have a sense that FDA is granting more or less leeway of how to select those natural history patients compared with what you presented in the July presentation? And thirdly, on the magnitude of neurofilament light chain reduction at year two from baseline, do you think for the BLA, the number of patients from the high-dose cohort may not be the same as what you were presenting in July.
I was wondering, given that this will be a supportive endpoint, is there a requirement that a certain degree similar to what you presented has to be achieved at year two? Or could it be even an increase potentially? Still, this could support approval. Sorry for the multitude of questions.
Okay. Thanks for the questions. Let me just try to kick them off. And again, I'll encourage Walid to join in. So in terms of the safety base, let me just repeat that very shortly. We're going to have 45 patients in total treated with AMT-130, with the first patient achieving, I believe, five years of follow-up next year, and an increasing number of patients with more than three years, and everybody from the first two cohorts with at least two years of follow-up next year. So I mean, our view is that this represents a substantial safety database that I think should give the agency comfort that this is generally safe and well tolerated. Obviously, we need to have additional conversations with the FDA, but that's our perspective. On the natural history, again, the details have to be discussed at later meetings.
I think the most important point is that the FDA understands the difficulty in administering a properly internally controlled blinded study and has accepted that the natural history, given how much is available in Huntington's disease, can potentially provide accelerated approval or support of an accelerated approval. To me, that's the most important thing. And there's obviously some details that have to be discussed, but those we can get to in the next year or the new year. And then in terms of NfL reductions, I think the important thing here there was no conversation about specific requirements of what number it had to be at or what the flexibility was.
I think what was clear is that the FDA understands NfL, understands that it is generally a very well-characterized marker for neurodegeneration, and appreciates the fact that reductions in CSF NfL indicate lower levels of neurodegeneration happening, which is clearly not expected as Huntington's disease progresses, so I think all of these things are, I think, incredible progress that we've made in a singular meeting and will provide some additional details as we have additional meetings with the FDA next year.
Great. Thanks for the answers, and congrats again.
Thank you. Again, ladies and gentlemen, if you have a question or comment at this time, please press star 11 on your telephone keypad. I'm sure no additional questions in the queue at this time. I'd like to turn the conference back over to management for any closing remarks.
Okay. Thank you, everybody, for joining us today. I'd also like to give a special thanks to the uniQure team for their unwavering dedication to our mission in the Huntington's disease community, for all of your support and partnership over the years. We deeply appreciate the FDA's recognition of the urgency to address the unmet medical need clearly present in Huntington's, and we very much look forward to providing additional program updates in the new year. Thank you very much, and have a great day.
Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone, have a wonderful day. Speaker standby.