Cuộc họp báo cáo kết quả kinh doanh Quý 3/2026 của uniQure (QURE): Xem xét ưu tiên đối với AMT-130 và dòng tiền hoạt động đến năm 2030

Điểm tin chính

• FDA đã chấp thuận đơn xin cấp phép sinh học (BLA) cho AMT-130 của uniQure để xem xét ưu tiên, với ngày mục tiêu PDUFA là ngày 1 tháng 5 năm 2027. Cơ quan Quản lý Sản phẩm Y tế và Chăm sóc Sức khỏe Vương quốc Anh (MHRA) cũng đã phê duyệt đơn xin cấp phép lưu hành.
• Tại thời điểm 36 tháng, liều cao AMT-130 làm giảm 75% tiến triển của bệnh Huntington theo thang cUHDRS và giảm 60% theo thang TFC so với nhóm đối chứng bên ngoài ghép cặp điểm xu hướng. Cả hai kết quả đều có ý nghĩa thống kê.
• Nghiên cứu xác nhận theo kế hoạch sẽ tuyển chọn khoảng 200 bệnh nhân, phân bổ ngẫu nhiên theo tỷ lệ 2:1 giữa liều cao AMT-130 và chăm sóc tiêu chuẩn. Tiêu chí đánh giá chính là chỉ số TFC tại thời điểm 36 tháng, và việc sàng lọc bệnh nhân dự kiến bắt đầu vào cuối năm 2026.
• Doanh thu quý 3 năm 2026 tăng 1,5 triệu USD so với cùng kỳ năm ngoái lên 5,2 triệu USD, nhờ doanh thu từ cấp phép tăng. Chi phí R&D là 35,5 triệu USD, trong khi chi phí SG&A tăng lên 23,9 triệu USD do mở rộng các hoạt động chuẩn bị thương mại hóa.
• Tiền, các khoản tương đương tiền và chứng khoán đầu tư đạt tổng cộng 768,4 triệu USD vào ngày 30 tháng 9 năm 2026. Ban lãnh đạo dự kiến các nguồn lực này sẽ tài trợ cho các hoạt động đến năm 2030.
• Đối với khả năng ra mắt tại Mỹ, uniQure dự kiến ban đầu sẽ có hơn 15 trung tâm điều trị sẵn sàng, mặc dù con số cuối cùng có thể đạt 25 hoặc 30. Ban lãnh đạo kỳ vọng mức độ tiếp nhận ban đầu chủ yếu bị hạn chế bởi công suất của trung tâm điều trị hơn là nhu cầu.

Dữ liệu tài chính chính

Chi phí R&D bao gồm khoản giảm 4,1 triệu USD chi phí thẩm định quy trình AMT-130, được bù đắp một phần bởi khoản tăng 1,5 triệu USD cho AMT-260 và 1,7 triệu USD cho các hoạt động tiền lâm sàng và đổi mới công nghệ.

Kết quả kinh doanh và hoạt động

Tiến trình pháp lý và lâm sàng của AMT-130

Đơn xin cấp phép sinh học (BLA) của AMT-130 tại Mỹ đang trong quá trình xem xét ưu tiên tích cực. FDA đã thông báo sơ bộ rằng cơ quan này có thể thảo luận về đơn nộp tại một cuộc họp ủy ban cố vấn, mặc dù việc sắp xếp lịch trình vẫn do cơ quan này quyết định.

Các hồ sơ nộp lên cơ quan quản lý dựa trên phân tích 36 tháng của AMT-130. Trong suốt các nghiên cứu Giai đoạn I/II, các bệnh nhân dùng liều cao ghi nhận mức giảm TFC hàng năm dưới 0,1 điểm, và kết quả này được duy trì qua 4 năm sau khi điều trị. Ban lãnh đạo thừa nhận rằng tập dữ liệu này liên quan đến một số lượng bệnh nhân tương đối nhỏ.

uniQure đã đạt được sự thống nhất với FDA về các yếu tố then chốt của thử nghiệm xác nhận. Nghiên cứu toàn cầu này sẽ bao gồm các điểm thử nghiệm tại Bắc Mỹ, Châu Âu và Mỹ Latinh. Sau 36 tháng, những người tham gia nhóm chăm sóc tiêu chuẩn sẽ được cho sử dụng AMT-130 thông qua một nghiên cứu mở riêng biệt.

Công tác chuẩn bị thương mại hóa

Công ty đang xây dựng đội ngũ y tế, tiếp cận thị trường, quản lý khách hàng chiến lược và đội ngũ địa bàn trước đợt ra mắt tiềm năng tại Mỹ vào năm 2027. Chiến lược trung tâm điều trị của công ty tập trung vào các cơ sở kết hợp chuyên môn về bệnh Huntington, khả năng phẫu thuật thần kinh dưới sự hướng dẫn của hình ảnh và hạ tầng cần thiết cho việc xử lý sản phẩm cũng như theo dõi bệnh nhân.

Ban lãnh đạo cho biết công suất điều trị có sự chênh lệch đáng kể giữa các trung tâm, dao động từ khoảng hai ca thủ thuật mỗi tuần đến một ca mỗi tháng. Sự phê duyệt của cơ quan/tổ chức, khả năng tiếp cận của bên thanh toán và mức độ sẵn sàng của trung tâm có thể ảnh hưởng đến tốc độ điều trị ban đầu.

Tại Vương quốc Anh, uniQure đã bắt đầu làm việc với NICE và NHS England. Sau khi nhận được sự phê duyệt tiềm năng từ MHRA, việc hoàn trả chi phí sẽ cần sự đánh giá của NICE và việc đưa vào sử dụng trong các hệ thống y tế liên quan của Vương quốc Anh.

Các chương trình phát triển sản phẩm khác

Khâu tuyển chọn đã hoàn tất ở nhóm 7 bệnh nhân dùng liều cao hơn trong nghiên cứu Giai đoạn I/IIa của AMT-260 đối với bệnh động kinh thùy thái dương trong kháng thuốc. Ban lãnh đạo dự kiến cập nhật kết quả từ cả hai nhóm liều trong nửa đầu năm 2027. Ở nhóm 6 bệnh nhân dùng liều thấp, khoảng một nửa cho thấy kết quả khả quan, trong khi các bệnh nhân còn lại phản ứng kém hơn.

Việc tuyển chọn bệnh nhân cho các nhóm liều trung bình và liều cao trong nghiên cứu bệnh Fabry của AMT-191 đã được khởi động lại vào tháng 8. Việc dùng thuốc từng bị tạm dừng theo đề cương thử nghiệm sau khi xuất hiện tình trạng tăng enzym gan không triệu chứng, tình trạng này đã thuyên giảm hoàn toàn sau khi điều trị bằng thuốc ức chế miễn dịch. Dữ liệu cập nhật từ cả ba nhóm liều dự kiến sẽ có trong nửa đầu năm 2027.

Hướng dẫn của Ban lãnh đạo

• Tiền, các khoản tương đương tiền và chứng khoán đầu tư dự kiến sẽ tài trợ cho các hoạt động đến năm 2030, bao gồm các chương trình lâm sàng và công tác chuẩn bị ra mắt AMT-130.
• Chi tiêu SG&A dự kiến sẽ tăng khi công ty xây dựng các năng lực thương mại, mặc dù ban lãnh đạo không đưa ra hướng dẫn chi phí cụ thể.
• Đội ngũ ra mắt AMT-130 nòng cốt dự kiến sẽ hoàn thiện vào đầu năm 2027, trước ngày PDUFA là ngày 1 tháng 5 năm 2027.
• Dữ liệu lâm sàng cập nhật của AMT-260 và AMT-191 dự kiến sẽ có trong nửa đầu năm 2027.

Rủi ro và yếu tố cần theo dõi

• FDA có thể triệu tập một ủy ban cố vấn để xem xét AMT-130. Ủy ban, thời gian và các chủ đề thảo luận vẫn chưa được xác định.
• Yêu cầu cung cấp dữ liệu 4 năm của AMT-130 có thể trở thành một sự điều chỉnh lớn và làm chậm ngày PDUFA nếu FDA phân loại như vậy. Ban lãnh đạo cho biết tính đến thời điểm cuộc gọi, cơ quan này vẫn chưa yêu cầu dữ liệu đó.
• Sự sẵn có trên thị trường thương mại có thể làm tăng rủi ro bỏ cuộc ở nhóm chăm sóc tiêu chuẩn của nghiên cứu xác nhận. uniQure lên kế hoạch tuyển chọn bệnh nhân trên toàn cầu, bao gồm cả các khu vực mà AMT-130 có thể chưa có sẵn thương mại trong thời gian thử nghiệm, và đã điều chỉnh quy mô mẫu cũng như kế hoạch phân tích cho sự sụt giảm số lượng bệnh nhân tiềm năng.
• Nhãn sản phẩm cuối cùng của AMT-130 vẫn tùy thuộc vào sự xem xét của FDA. Kế hoạch thị trường có thể tiếp cận hiện tại của ban lãnh đạo giả định các yêu cầu về thể tích thể vân.
• Năng lực thương mại ban đầu có thể bị giới hạn bởi công suất phẫu thuật thần kinh, sự phê duyệt của viện/tổ chức, việc hoàn trả chi phí và thời gian cần thiết để đưa các trung tâm điều trị vào hoạt động.

Điểm tin hỏi đáp của chuyên viên phân tích

• Triển khai nghiên cứu xác nhận: Ban lãnh đạo không đưa ra mục tiêu tuyển chọn bệnh nhân cho đến ngày PDUFA nhưng cho biết nghiên cứu sẽ diễn ra thuận lợi vào thời điểm đó. Công ty ban đầu sẽ ưu tiên tuyển chọn tại Mỹ trước khi mở rộng sang các điểm thử nghiệm toàn cầu.
• Thiết kế và sự biến động của nghiên cứu: Tiêu chuẩn chọn bệnh nhân dự kiến sẽ tương tự như chương trình Giai đoạn I/II, bao gồm các yêu cầu về thể tích thể vân. Việc đào tạo tại điểm thử nghiệm và sự hợp tác với Nhóm Nghiên cứu Bệnh Huntington nhằm mục đích chuẩn hóa việc đánh giá TFC.
• Sản xuất: Ban lãnh đạo không kỳ vọng năng lực sản xuất sẽ hạn chế việc ra mắt. AMT-130 sử dụng khoảng 500 microliter cho mỗi lần truyền, cho phép điều trị cho nhiều bệnh nhân hơn trên mỗi lô sản xuất so với liệu pháp tiêm truyền tĩnh mạch.
• Quy trình điều trị: Công ty đang đánh giá các điều chỉnh quy trình có thể làm giảm thời gian và độ phức tạp của phẫu thuật thần kinh sau khi được phê duyệt.
• Khả năng không được phê duyệt: Ban lãnh đạo cho biết uniQure vẫn cam kết hoàn thành nghiên cứu AMT-130 ngay cả khi sản phẩm không được phê duyệt trước ngày PDUFA, trong trường hợp đó thử nghiệm có thể hoạt động như một nghiên cứu đăng ký Giai đoạn III thay vì một nghiên cứu xác nhận sau phê duyệt.

Toàn văn bản ghi cuộc gọi báo cáo kết quả kinh doanh

Toàn văn cuộc gọi công bố kết quả kinh doanh

Phần trình bày của ban lãnh đạo

Operator

Hello, and thank you for standing by. My name is John, and I will be your conference operator today. At this time, I would like to welcome everyone to the uniQure Third Quarter 2026 Earnings Call. [Operator Instructions]

I would now like to turn the call over to Chiara Russo, Senior Director of Investor Relations.

Chiara Russo

Thank you. Good morning and thank you for joining us for uniQure's third quarter of 2026 earnings call. Earlier this morning, uniQure released its financial results for the third quarter of 2026, and our press release is available on the Investors and Media section of our website at unicure.com. Our 10-Q was also filed with the SEC earlier 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 up for an analyst Q&A.

Before we begin, please note that we'll be making forward-looking statements during this investor call. All statements other than statements of historical fact are forward-looking statements. They are based on management's beliefs and assumptions and on information available to management only as of the date of this conference call. 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 information becomes available in the future.

Now let me introduce Matt Kapusta, uniQure's CEO.

Matthew Kapusta

Good morning, and thank you for joining us on today's call. For the families who have waited generations for treatment for Huntington's disease, this quarter brought meaningful progress. As we announced on Monday, the FDA has accepted our biologics license application for AMT-130 and granted priority review with a target PDUFA date of May 1, 2027. In the United Kingdom, the MHRA has also validated our marketing authorization application.

These are the first such marketing applications for a disease-modifying therapy for Huntington's disease, and it brings patients and families one step closer to a treatment option. We greatly appreciate the engagement of both the FDA and the MHRA and their focus on the critical need for new therapies in Huntington's disease.

I also want to acknowledge the commitment of our clinical, regulatory and CMC teams who prepared and submitted both applications in record time. And to every HD patient, family member and investigator who has trusted us with their hope, thank you.

In September, we shared additional data from our ongoing Phase I/II studies, including updated 36-month data from all 27 evaluable patients across the low- and high-dose cohorts and for the first time, 48 months of follow-up after a single administration of AMT-130. These data continue to show meaningful dose-dependent slowing of disease progression and reinforce our strong belief that AMT-130 has the potential to deliver treatment benefit to patients.

We are also pleased to have aligned with the FDA on the key elements of the confirmatory study design, and we are making significant progress getting the trial up and running. We are fully committed to the timely execution of this study, and our priority is to have it well underway at the time of an approval decision. Walid will provide more detail on the confirmatory study later in the call.

Regarding commercial preparations, we are making excellent progress ahead of potential U.S. launch in 2027. We continue to build out our field, medical, market access and strategic account teams in a disciplined way and our financial strength provides the runway needed to execute this build-out. Kylie and Christian will provide more details on our commercial readiness and financial position later on the call.

Beyond AMT-130, we continue to advance our broader pipeline. We have completed enrollment in the second dose cohort of our Phase I/IIa study of AMT-260 in refractory mesial temporal lobe epilepsy and have resumed enrollment in the Phase I/II study of AMT-191 in Fabry disease. For both programs, we expect to present new and updated data in the first half of 2027.

In summary, we are heading into the end of 2026 with strong momentum. Our priorities are clear, working closely with regulators as the application reviews proceed, executing our confirmatory study, advancing our pipeline and building the organization to prepare for the planned launch of AMT-130.

With that, I will turn the call over to Walid to provide additional detail on AMT-130 and our pipeline. Walid?

Walid Abi-Saab

Thank you, Matt. Good morning and good afternoon, everyone. I'll start with AMT-130 in Huntington's disease, or HD. As Matt noted, the BLA is under priority review with the PDUFA date of May 1, 2027, and the MAA has been validated by the MHRA. Both submissions are based on the 36-month analysis we presented in September 2025. In that analysis, the high dose of AMT-130 showed a 75% slowing of disease progression on the composite Unified Huntington's Disease Rating Scale, or cUHDRS, and a 60% slowing on total function capacity or TFC, compared with the propensity score matched external control. Both results were statistically significant.

With the BLA now accepted and under active review, going forward, we will not be commenting on specific information requests made by the FDA, including questions regarding a potential AdCom. The FDA indicated that they are tentatively planning to discuss our application at an AdCom. As you're aware, scheduling an AdCom is within the sole discretion of the agency.

In September 2026, we presented detailed analysis of a recent data cutoff. I will not repeat that today. Instead, I would like to focus on the progress we've made towards initiating the confirmatory study. Earlier this year, we reached alignment with the FDA on key elements of the design. Specifically, this will be a randomized study with a 2:1 ratio of AMT-130 high dose to standard of care. It will include approximately 200 patients. The primary endpoint is TFC at 36-month. After 36-month, all standard of care participants will be offered AMT-130 in a separate open-label study.

uniQure is fully committed to completing the study in a timely manner. Preparations started at the beginning of this year and have accelerated following alignment with the FDA. This will be a global study with sites across North America, Europe and Latin America. The protocol has already been submitted to institutional review boards or IRBs in the U.S., and we expect to begin patient screening by the end of this year.

I would like to take a moment to talk about TFC, the primary endpoint in the confirmatory study. This is a clinical endpoint that is very important, not only for regulators but also for people living with HD.

Why is TFC important? TFC captures whether a person can keep working, manage their finances, handle household responsibilities, take care of themselves day-to-day and live without full-time care. For patients and families, these are not abstract measures. They are the difference between maintaining and losing independence, and they are directly related to quality of life.

This is what patients and families care about. In fact, it is what we heard from HD specialists at the 2 most recent scientific meetings we attended, the International Parkinson and Movement Disorder Society meeting in Seoul and the European Huntington's Disease Network meeting in Krakow. These specialists describe TSC as the endpoint they find most meaningful when talking with patients.

Across our Phase I/II studies, TFC declined by less than 1/10 point per year in patients who received a high dose of AMT-130. This remarkably slow decline was consistent across all analyses and maintained through 4 years following treatment. Although these results come from a relatively small number of patients, they have never been seen before in HD.

Moving on to our other clinical programs, starting with AMT-260 for refractory mesial temporal lobe epilepsy. Following the initial 6-month data of the first low-dose cohort of 6 patients, which was presented in June, early in this quarter, we completed enrollment of the second cohort of 7 higher dose patients. We expect to present updated results from both cohorts in the Phase I/IIa study in the first half of 2027.

Turning to AMT-191 for Fabry disease. In August, enrollment resumed in the mid- and high-dose cohorts. As a reminder, dosing has been paused per protocol in these 2 cohorts after asymptomatic liver enzyme elevations, which fully resolved following a course of immunosuppression. We presented updated results in June from the March 15 cutoff, and we expect to share updated results from all 3 dosing cohorts in the first half of 2027.

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

Kylie O'Keefe

Thanks, Walid. With a known PDUFA date ahead of us, the question for our customer-facing team is no longer when. It's how. How do we make sure every piece of this patient journey is in place and well supported by the PDUFA date. So if approval is granted, we are ready to launch. For AMT-130, that journey runs from identifying an eligible patient through evaluation, surgery, follow-up and reimbursement. It involves many critical stakeholders.

Our job is to ensure a smooth process for patients, families and the clinicians who care for them. For many of these families, the patient journey already runs through a familiar place, a specialty HD clinic they have relied on for years. That is an important feature of this market as HD care is concentrated. A large share of diagnosed patients are seen at a number of specialty centers, many of them HDSA Centers of Excellence. That concentration will allow for a focused launch footprint.

We continue to see strong enthusiasm from the physician and patient community. This quarter, our team spent significant time with the Huntington's disease clinical and patient communities. That included the International Congress of Parkinson's Disease and Movement Disorders, or MDS, and the EHDN Clinical Research Congress. These meetings came shortly after we submitted our BLA and U.K. MAA and shared our recent data. That gave us a timely chance to hear directly from the physicians who care for HD patients every day.

Our ongoing interactions tell us that physicians and families place great weight on preserving function and independence. And that is why the total functional capacity data Walid described resonates so strongly. We expect uptake to be shaped mainly by treatment center capacity in the early launch period, not by demand. That's why center readiness is our top operational priority and preparing to allow them to be operational as quickly as possible after a potential approval.

Moving on to identifying treatment centers. AMT 130 is a one-time administered therapy through a neurosurgical procedure. Each treatment center, therefore, needs 3 capabilities working together. HD neurology expertise to identify and evaluate patients, neurosurgical teams experienced in image-guided delivery and the ancillary infrastructure to support the procedure and product handling.

We have identified priority centers in the U.S. and the U.K. Our readiness work at these centers covers 3 key areas: first, neurosurgical training and procedural support; second, product handling; and third, patient evaluation and referral pathways. Our goal is for a meaningful number of centers to be ready to treat eligible patients soon after a potential approval.

Finally, access and our ongoing work with payers. We have been engaging with access stakeholders through appropriate preapproval information exchange. These initial conversations cover the burden of Huntington's disease, the clinical data package and the economic profile of a onetime therapy. From early discussions, payers recognize the high unmet need in HD and the lack of any approved disease-modifying therapies. And there is a strong interest in learning more about AMT-130.

In the U.K., we have begun engaging with NICE NHS England and are planning for health technology assessments so that access can follow as closely as possible after any potential MHRA decision.

Finally, we continue to build the team that will make this launch a success. We expect to have our core team fully in place by early next year ahead of the PDUFA date. We're hiring with care, bringing in people with deep experience in rare disease gene therapy and neurology launches.

To summarize, we are preparing with urgency and discipline. Our goal is that if AMT-130 is approved, patients can move from referral to treatment as efficiently as possible.

With that, I'll turn the call over to Christian for a financial update. Christian?

Christian Klemt

Thank you, Kylie. I'll now be sharing the financial highlights of the third quarter of 2026. Please refer to the earnings press release issued this morning and our quarterly filings with the SEC for additional detail.

Revenue for the 3 months ended September 30, 2026, was $5.2 million compared to $3.7 million in the same period in 2025. The increase of $1.5 million is due to an increase in license revenue compared to the prior period.

Research and development expenses were $35.5 million for the 3 months ended September 30, 2026, compared to $34.4 million during the same period in 2025. The $1.1 million increase was primarily driven by $3.6 million increase in employee contractor-related expenses, including share-based compensation, which was partially offset by a $2.3 million decrease in direct research and development expenses. The decrease in direct research and development expenses resulted from a $4.1 million reduction in process validation expenses related to AMT-130, a $1.5 million increase in expenses related to AMT-260 and a $1.7 million increase in expenses related to preclinical activities and technology innovation projects.

Selling, general and administrative expenses were $23.9 million for the 3 months ended September 30, 2026, compared to $19.4 million during the same period 2025. The $4.5 million increase was primarily related to a $3 million increase in employee and contractor-related expenses, including share-based compensation, mainly as a result of the recruitment efforts over the last 12 to 15 months, a $0.7 million increase in professional fees and a $0.7 million increase in information technology costs to support the potential commercial launches of AMT-130.

Cash, cash equivalents and investment securities totaled $768.4 million as of September 30, 2026, compared to $622.5 million as of December 31, 2025. We believe that uniQure continues to be well positioned to execute on its clinical and operational priorities. We expect that cash, cash equivalents and investment securities will be sufficient to fund operations into 2030.

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

Matthew Kapusta

Thank you, Christian. As you've heard today, the third quarter of 2026 was an important one for uniQure and for people impacted by Huntington's disease. We believe that AMT-130 has demonstrated a meaningful slowing of disease progression and has the potential to provide treatment benefit for people living with Huntington's disease. We now look forward to working with the regulatory agencies to bring AMT-130 to patients as soon as possible.

With that, operator, please go ahead and open the call for questions.

Operator

[Operator Instructions] So our first question comes from the line of Debjit Chattopadhyay with Guggenheim Securities.

Phần hỏi đáp

Debjit Chattopadhyay

I have a couple. First on AMT-130, if it becomes commercially available in the U.S. next year, how are you modeling potential dropouts from the standard of care cohort in the confirmatory study?

And number two, are you evaluating any alternative delivery approaches to potentially expedite the procedure times?

Matthew Kapusta

Debjit, it's Matt here. Walid, do you want to take the first question on the confirmatory study?

Walid Abi-Saab

Sure. I'd love to. Yes. So Debjit, this is going to be a global clinical study. Early on, we're going to be prioritizing recruitment in the U.S. to get us up and running and be meaningfully recruited, but the reach will be global such that during the conduct of the study, we will be -- we will go to places where we will not be having AMT-130 on the market during the conduct of the study, and that will reduce this.

In addition to this, we're doing a number of simulation, and we have adjusted our sample size to match this. So this eventuality as well, as well as sort of analysis plans to deal with dropouts whenever they happen in the SOC. I turn it over to you, Matt.

Matthew Kapusta

Yes, Debjit, on the second question, there is actually a significant amount of work that's going on now looking at procedural adaptations. And these would be things that would potentially be implemented post approval. But a number of these things have the potential to meaningfully reduce procedural time and complexity.

Operator

Next question comes from the line of Paul Matteis with Stifel.

Matthew Ryan Tan

This is Matthew on for Paul. Congrats on the progress. I guess maybe a question for Kylie. How quickly would you anticipate patients will be able to get therapy, assuming the positive outcome from the PDUFA? And what would be the gating factor there? Would it be access?

And then another quick follow-up. For the confirmatory study, would the eligibility criteria be similar to the Phase I/II, including the stage of the disease and maybe the striata volume requirements?

Kylie O'Keefe

Thank you very much for the first question. So with regards to what could potentially be gating factors, I think there's 2 elements to this. Access is, of course, one of them as well as ensuring that we have P&T approvals in the individual institutions to ensure that patients can get access to the therapy and that the institutions can get paid for that.

However, what I would say, while these are traditional gating factors, the team is working very hard to ensure that we do as much preparation as possible ahead of a potential launch to ensure that this is streamlined in the best possible way. So there's a lot of work going on in all the institutions to map the P&T processes, understand how often do they meet what are the requirements that are needed to secure approval and ensure that we're working with the institutions to provide as much information in advance so that it's streamlined at the point of launch.

In addition to that, as I mentioned in the prepared remarks, the team is also working with payers on educating across both the unmet need in Huntington's disease as well as the AMT-130 data package to ensure that we're able to move as quick as possible post launch.

Walid Abi-Saab

So regarding the eligibility for the confirmatory study, that will be similar to the -- what we did report the Phase I/II, including the striatal volume as well.

Operator

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

Joseph Schwartz

Congrats on all the progress. Given the FDA expects the confirmatory study to be well underway and potentially fully enrolled at the time of accelerated approval, and screening starts by year-end and the decision date is about 4 months later on May 1. We were wondering how many patients do you expect to have randomized or dosed by then?

And then for the advisory committee, how do you keep the discussion on the 36-month analysis, which the FDA agreed supports the BLA rather than rearguing the 48-month primary analysis? And then any sense yet of timing or which committee?

Matthew Kapusta

Joe, thanks for the questions. Walid, do you want to take them one by one?

Walid Abi-Saab

Sure, happy to. So the FDA's fundamental intent for the confirmatory studies based on their January 25 guidance is that to make sure that they can be completed in a timely manner after approval. And we are confident we can demonstrate that. We've been starting -- we started to prepare for the study before we engaged fully with the FDA. And after we aligned with them, we accelerated that.

Our goal is to run the study globally, as I indicated, across the U.S., Canada, North America, Latin America and Europe. And we intend also to run it in places where there will not be access during the trial so that there will be lower risk of dropout, which is when the agency is, to a great extent, worried about it if we cannot complete the study.

So with all of these elements in place and making sure that we demonstrate to the agency the full engagement and all the sites across the world that we've engaged with and the momentum for enrollment, we believe that we can present a credible path that would satisfy the agency.

Regarding the AdCom and 48 versus 36-month, it's premature for us to position this. We will be ready to discuss any action. But to a great extent, that will be depending on the agency's briefing book. As you know, in preparation for the AdCom, we are -- we will be preparing for any possible scenario. And we will have to gauge this based on what our specific questions are going to be raising for the AdCom and the briefing book supporting that. So we will get a chance to adjust in due course.

And regarding the committee, I do not have any more information on this, definitely not from the FDA, but I would imagine it will be the typical committee that reviews cell and gene therapy and advanced therapies.

Operator

Next question comes from the line of Luca Issi with RBC Capital Markets.

Luca Issi

Congrats on the progress. Maybe, Walid can you confirm that you have yet to receive the day 74 letter? And then maybe bigger picture, can you just maybe educate us on what is usually included in that letter? Do you think the FDA will share some of their preliminary concerns in the context of the letter? I guess what I'm trying to ask here is whether there could be anything material in the letter that you need to disclose to the Street as well or not?

And then maybe super quickly, SG&A obviously went up a little bit versus last year, you obviously preparing for the launch. How should we think about the line item going forward maybe before and after the PDUFA?

Walid Abi-Saab

Yes. Thanks, Luca. Look, as we have indicated that since now, we are in active review process, we will not be providing any updates based on request for information or any other communication with the FDA. Of course, we will respond to them in due course. But unless things are material, we will not be communicating externally.

In terms of usually comes at day 74, that would be one example. If the agency has -- they list their areas of concern and areas that they're focused on, that's usually part of that day 74.

Matthew Kapusta

Christian, do you want to answer the SG&A question?

Christian Klemt

Sure, happy to. Look, as you know, we don't give specific guidance. It shouldn't be surprised that SG&A spend will go up, but we'll maintain our disciplined approach. And it's all built into the runway guidance that we are capable of funding all our products into 2030.

Operator

Next question comes from the line of Joon Lee with UBS.

Joon Lee

Upon approval in May, how many patients would you be ready to dose in the U.S. and U.K. depending on the approval in U.K., obviously? And what is your manufacturing capacity?

And last question, in the unlikely scenario where the FDA does not end up approving AMT-130, are you still obligated to complete the confirmatory trial?

Matthew Kapusta

Kylie, do you want to answer the first question on launch?

Kylie O'Keefe

Yes, absolutely. I think across the board from a patient perspective, it's a bit premature to provide specific patient estimates. I think what the team is working on extensively is ensuring that we're able to understand what the capacity is at each of the different centers, both in the U.S. and in the U.K. to understand what we think is a reasonable number of centers that need to be operationalized at launch to be able to try and meet the demand as quickly as possible.

So the team is working on that at the moment, and we're targeting a number of institutions that have both HDSA Centers of Excellence as well as ClearPoint in the same institution to ensure that patients are able to be evaluated, move to surgery and then back to neurology very seamlessly. And that is the work that's been ongoing. So while we are not quite there yet to give specific patient estimates, I think a reasonable analog is other gene therapies that have launched recently.

Matthew Kapusta

Yes. And maybe I'll answer the next 2 questions. Yes, on manufacturing capacity, we do not expect that to be a constraint. Remember, these are relatively small volumes that we're administering in a targeted and precise way per infusion, this is approximately 500 microliters. So the yields that we get in terms of number of patients that can be treated per batch is meaningfully higher than an IV administered medicine.

On the third question regarding the confirmatory study, obviously, if we're not approved at the PDUFA date, we have to understand the reasons why and what our next steps are going to be. If you're asking more about the obligations related to the confirmatory study, I mean, I certainly think we have a commitment to this patient community, and there would be an ethical obligation to continue with that study. I don't know if it's a legal obligation, but we're absolutely committed to the HD community and completing that study, whether or not the drug is approved and it's a confirmatory study or if it's a Phase III registrational study.

Operator

Next question comes from the line of Peyton Bohnsack with TD Cowen.

John Peyton Bohnsack

This is Peyton on for Joe. I guess, can you talk a little bit about the Phase III protocol or trial design and anything that's included to decrease any variability in the TFC measure or make sure that there is the highest chance to detect the difference between the 2 groups?

Matthew Kapusta

Sure. I assume you meant the confirmatory study, but Walid, why don't you answer that one?

Walid Abi-Saab

Yes. Thanks, Matt. Yes, I assume it was on the confirmatory study. So look, we take very good care to try and train the sites and do regular training to make sure that the measurement is really accurate. We're collaborating with HSG, where they are trying to standardize also the administration of the question for TFC. I mean TFC tends to be a bit less noisy. I mean, because this is not like subjective as much in terms of like to what degree you have an abnormal movement in various parts of your body like TMS, which has been shown to be excessively variable. TFC talks about like really crude measures. Can you work full-time? Can you work part time? Can you take care of yourself? And those tend to be a bit much more consistent, I should say. And so we will be doing -- was there another part of the question that I'm missing?

Matthew Kapusta

No. I think he asked about...

Walid Abi-Saab

[indiscernible] Yes. And I wanted to mention also in powering the study, we also were careful. Of course, we don't want to be skating too close to the edge. We base it on information that we have from our ongoing study and took the necessary precautions to make sure that we will have enough power also considering potential dropout in the standard of care patients in the event that happens.

Operator

Next question comes from the line of Salveen Richter with Goldman Sachs.

Salveen Richter

On the launch here, how many certified neurosurgical centers do you expect to be fully trained and operationally prepared to dose commercial patients at approval? And what is the target throughput capacity here?

And then maybe you could just also speak to how you're thinking about the label and whether it will reflect the broad Phase I/II inclusion criteria or whether it's restricted to specific striatal volume thresholds?

Kylie O'Keefe

Absolutely. So starting with the first question on number of neurosurgical centers and capacity. I think one of the things that is important to note is neurosurgical capacity differs quite dramatically from center to center. And so again, this has been a lot of the work that the team has been doing to understand how many functional neurosurgeons would be able to perform the procedure, how many operating rooms are in place that could be used and then calculating capacity based on those discussions with the centers.

And so you see sometimes something from 2 a week to one a month, and it varies center to center. So the team has been really thinking through what is the capacity at each institution. And as you look across the institutions, how does that scale up on a national level. We're still working through the number that we think will be available at launch. We're certainly going to be north of 15 centers. Could it be 30? Could it be 25? We're still working through that to understand what that could look like and how quickly we can operationalize these centers.

But we're looking at centers with the highest potential capacity initially and then also adding additional centers from there. With regards to the second part of the question associated with the label, I think it's a bit premature for us to comment on that. We're not at the stage of discussing the label with the FDA. However, the way we've thought about the addressable market is assuming stratal volume requirements. And then obviously, if that's not the case, then we would adjust that accordingly.

Operator

Moving on to our next question. It comes from the line of Yanan Zhu with Wells Fargo.

Matthew Kapusta

I think we should go to the next question, operator.

Operator

Next question comes from the line Ellie Merle with Barclays.

Eliana Merle

Just a follow-up to the earlier question on the number of patients that you anticipate having dosed in the confirmatory trial at the time of like potential approval. I guess, do you have plans to submit additional safety data to the FDA prior to accelerated approval after some of the patients in the confirmatory study have received the initial procedures?

And then just a follow-up question on kind of like additional submissions to the FDA. I guess, if the FDA asked for the 4-year data, would that potentially warrant a major amendment as part of the review and how you're thinking about that as a potential scenario?

Matthew Kapusta

Thanks, Ellie. Walid, do you want to answer those?

Walid Abi-Saab

Sure. Regarding the number of patients, we're -- we are confident that we will be well underway by the time we reach PDUFA. And as I mentioned before, we have a lot of measures in place to be able to complete the study in a timely manner across the world. So pretty comfortable with that.

In terms of the safety data, we will be providing a day 120 safety update, which is typical in this situation. And of course, if there's any patients that have been dosed in the confirmatory trial by that cutoff date, those would be included, should be any patient available by that time.

Regarding the 4-year data, there's been no discussion with the FDA to date regarding the 4-year data in terms of requesting it. But as I mentioned before, if this were to happen during the course of the review, we will not be communicating on this because during the process, unless something is material, we will not be communicating on this. Now as you mentioned, in the event they ask for it, we submit it and they consider that a major amendment and there will be a delay to PDUFA. Of course, that will become material, and we will be sharing that information with you.

Operator

Our next question comes from the line of Patrick Trucchio with H.C. Wainwright.

Luis Santos

Luis Santos in for Patrick. The question is focused on trying to understand a little bit what could happen in the U.K. and what steps need to happen assuming MHRA approval for fully funded?

And then I would like to also ask a question on your epilepsy data coming up. And I was thinking if you could tell us a little bit more about how do you expect consistency in the patients that were treated with lower dose to inform the expectations for the higher dose?

Matthew Kapusta

Thanks for the questions. Do you want to answer the first question, Kylie, on the U.K.?

Kylie O'Keefe

Absolutely. Thanks, Matt. So with regard to your question around what happens from an access point of view to ensure that AMT-130 can be available for patients in the U.K. What would happen is we would undergo a NICE review. And from there, assuming success, we would begin NHS commissioning, NHS England, NHS Wales and so on and so forth, we would be commissioning with each of the individual countries in the U.K.

So what we have done is begun engaging from an early scientific point of view with both NICE and NHS England to ensure that we're able to understand how they're viewing Huntington's disease, how they're viewing the AMT-130 package. And then ultimately, we'll be in a position next year to be submitting the dossier to ensure that we're starting that process immediately upon approval.

Walid Abi-Saab

So for the AMT-260 question in MTLE, the really Phase I studies are there to learn. We dosed 6 patients in the low-dose cohort. We had great results in probably half the patients, and the others did not respond as well. We continue to follow them, and we will provide you also an update during the first half of next year on those patients.

In addition, we now fully dosed 7 more patients in the higher dose cohort. And depending on the results, we will be able to interpret the data, one possibility. If we find very consistently positive results, then there would be one interpretation. If that's not the case, then we need to figure out what would be the next step. So those would be part of the evaluation that we will do, and we will be sharing that information with you in the first half of next year.

Another element we do in the Phase I study is to look at safety. And in the first cohort, that profile was fairly good at this stage of development. So we were encouraged by that, and that allowed us to go to the higher dose cohort. And again, we will be sharing with you the results in the first half of the year.

Operator

Next question comes from the line of Rudy Li with Wolfe Research.

Unknown Analyst

This is Devin on for Rudy. Just had a question on AMT-260. Can you talk about the differentiation versus Neurona and RTX-1001? And what is the bar for a no-go versus a go decision for the ongoing study?

Matthew Kapusta

Walid, do you want to take that?

Walid Abi-Saab

Sure. Well, again, we're early in development. So our goal right now is to evaluate the risk benefit and -- of this product and see whether there's clear evidence of activity. Our goal in the end would be to be best-in-class, and that will determine -- but that will be determined after an appropriately well-controlled trial that we can do. At this point, we are still in the signal detection mode. And as always, we are very careful in making a go/no-go decision. So we're still gathering that information. We will share with you an update early next year. And based on that, we will tell you which direction based on these data, we will be going next.

Operator

Next question comes from the line of Lachlan Hanbury-Brown with William Blair Chicago.

Lachlan Hanbury-Brown

I wanted to follow up on one of the prior questions about the confirmatory trial. You mentioned FDA guidance about having to be sort of well underway at the time of accelerated approval. But I feel like we've kind of seen apply that standard differently across programs. So I was just wondering if you had any sort of explicit discussions with them on how they're thinking about that stand and what well underway means in this instance.

Matthew Kapusta

Yes. I think I'll maybe just -- I think it's really the same answer to the question that Walid has mentioned previously. The FDA does have a wide discretion to determine what is meaningfully underway. The spirit of this, which applies to really all accelerated approvals, is that they want to ensure that the execution of confirmatory evidence generation is done in a timely manner.

We -- they obviously are aware that we just are starting the confirmatory study. We've shared with them approximate time lines as part of our communication. The progress that we're making in getting the study up and running is accelerating. We will have an initial focus on enrolling patients in the United States and centers that are already up and running. And we plan to have numerous centers outside the United States assuming the product is approved.

So we're very confident and very committed to the study that we can complete it in a timely manner and then generate the data that is sufficient to support full approval.

Operator

Now our final question comes from the line of Sushila Hernandez with VLK.

Sushila Hernandez

So for the confirmatory study, could you expand on the primary analysis being assessed at 36 months, what is supporting this time point?

And secondly, how many U.S. centers do you expect could administrate AMT-130 in the first 12 months after approval? How do you look at this development during the initial launch period?

Matthew Kapusta

Walid, do you want to take the first one? And then, Kylie, you can take the second?

Walid Abi-Saab

Sure. Yes. The primary analysis is essentially at 36 months TFC comparing our treated subjects to the standard of care control. Not sure if there's any need to elaborate more. This would be an MMRM analysis, which is typical of these types of studies. Kylie?

Kylie O'Keefe

Thanks, Walid. And with the second question, across the U.S., there's more than 60 HDSA Centers of Excellence. And then when you layer over the top of that centers that also have ClearPoint capabilities, you get to north of 100. This is obviously not what we're targeting in the first 12 months. And as I said earlier, that number has not been locked down yet. We're working through understanding the capacity at each of the different institutions in the U.S. and then trying to look at demand in the first 12 months and saying, what do we think is needed to be ready to go on day 1? And then ultimately, how do we build that up over the first 6 months, 12 months, 18 months and so on.

So we're going to be having a certain number of capacity at launch, which, as I said, is going to be north of 15 centers, whether it's 25, whether it's 30, that number has not been defined yet, and then we will build from there.

Operator

So this concludes the question-and-answer session and our call today. Thank you all for joining. You may now disconnect.