Cuộc họp báo cáo kết quả kinh doanh Quý 3/2026 của Acumen Pharmaceuticals (ABOS): Dự kiến công bố kết quả ALTITUDE-AD vào tháng 11

Tóm tắt điểm chính

• Acumen Pharmaceuticals dự kiến sẽ báo cáo kết quả sơ bộ từ thử nghiệm Phase II ALTITUDE-AD đối với sabirnetug vào tháng 11 năm 2026.
• Thử nghiệm kéo dài 18 tháng được thiết kế nhằm phát hiện sự khác biệt có ý nghĩa thống kê so với giả dược ở tiêu chí đánh giá chính iADRS. Ban lãnh đạo đã xác định mức làm chậm khoảng 30% trên thang iADRS là ngưỡng thành công lâm sàng rõ ràng để tiếp tục đẩy mạnh chương trình này.
• Bộ dữ liệu sơ bộ dự kiến sẽ bao gồm CDR Sum of Boxes, các biến cố bất lợi, tỷ lệ ARIA, chụp PET mảng xơ amyloid và các chỉ dấu sinh học trong dịch cơ thể bao gồm p-tau217.
• Acumen kết thúc quý 3/2026 với khoảng 79 triệu USD tiền mặt và chứng khoán có giá bán, điều mà ban lãnh đạo kỳ vọng sẽ đủ để tài trợ cho các hoạt động lâm sàng và vận hành hiện tại cho đến đầu năm 2027.
• Chi phí R&D trong quý 3 là 21,1 triệu USD, trong khi lỗ từ hoạt động kinh doanh và lỗ ròng lần lượt là 25,8 triệu USD và 25,4 triệu USD.
• Công ty cũng đang đẩy mạnh phát triển ACU-301 và ACU-401 thuộc chương trình tăng cường phân phối vào脑 bộ, dự kiến sẽ nộp hồ sơ xin phép thử nghiệm lâm sàng (IND) vào giữa năm 2027.

Dữ liệu tài chính trọng yếu

Kết quả hoạt động kinh doanh và vận hành

Sabirnetug tiếp tục là ứng viên lâm sàng chủ lực của Acumen. Kháng thể đơn dòng IgG2 chống lại oligomer A-beta chọn lọc này đang được đánh giá trong thử nghiệm ALTITUDE-AD với các liều 35 mg/kg và 50 mg/kg, truyền tĩnh mạch bốn tuần một lần. Ban lãnh đạo cho biết cả hai mức liều đều được lựa chọn dựa trên mức độ phơi nhiễm trong Phase I, dữ liệu dược lực học và mô hình hóa liều lượng, và cả hai đều có thể nằm trong phạm vi đạt hiệu quả điều trị.

Thử nghiệm Phase II sử dụng iADRS làm tiêu chí đánh giá hiệu quả chính sau 18 tháng điều trị. Acumen thiết kế nghiên cứu này như một thành phần tiềm năng trong hồ sơ đăng ký lưu hành. Nếu kết quả khả quan, công ty dự kiến sẽ thực hiện một thử nghiệm Phase III xác nhận.

Tỷ lệ duy trì bệnh nhân đã vượt kỳ vọng của ban lãnh đạo. Hơn 95% người tham gia đủ điều kiện đã chọn và đồng ý tham gia giai đoạn mở rộng công khai (open-label extension) kéo dài 12 tháng. Dữ liệu từ giai đoạn mở rộng đó dự kiến sẽ có trong năm 2027 và ít có khả năng được đưa vào báo cáo kết quả sơ bộ ban đầu.

Acumen cũng đang phát triển ACU-301 và ACU-401 thông qua chương trình tăng cường phân phối vào não bộ. ACU-301 kết hợp sabirnetug trong một kháng thể đặc hiệu kép, trong khi ACU-401 sử dụng kháng thể ACU-234. Trên động vật linh trưởng không phải người, ACU-401 đạt mức độ phơi nhiễm ở vỏ nền trán cao hơn tới 40 lần so với ACU-234 chưa biến đổi và tăng mức độ phơi nhiễm ở các vùng não sâu.

Định hướng của Ban lãnh đạo

Ban lãnh đạo dự kiến sẽ công bố dữ liệu sơ bộ của ALTITUDE-AD vào tháng 11 năm 2026. Báo cáo dự kiến sẽ bao gồm các kết quả hiệu quả chính và phụ, phát hiện về độ an toàn, tỷ lệ ARIA, cũng như các chỉ dấu sinh học chẩn đoán hình ảnh và dịch cơ thể.

Acumen kỳ vọng lượng tiền mặt khoảng 79 triệu USD sẽ đủ hỗ trợ các hoạt động hiện tại cho đến đầu năm 2027. Công ty đặt mục tiêu nộp hồ sơ xin phép thử nghiệm lâm sàng (IND) cho chương trình tăng cường phân phối vào脑 bộ vào giữa năm 2027.

Công ty có thể đưa dạng bào chế tiêm dưới da vào quá trình phát triển Phase III trong tương lai, nhiều khả năng thông qua giai đoạn mở rộng công khai. Phương án cuối cùng sẽ phụ thuộc một phần vào kết quả Phase II và việc lựa chọn liều lượng.

Rủi ro và Các điểm chính cần theo dõi

Việc công bố kết quả ALTITUDE-AD sắp tới là bài kiểm tra lâm sàng lớn đầu tiên đối với giả thuyết trung tâm của Acumen rằng việc nhắm mục tiêu chọn lọc vào các oligomer A-beta hòa tan có thể làm chậm sự tiến triển của bệnh Alzheimer. Trọng tâm chính sẽ là việc liệu một trong hai mức liều có mang lại lợi ích có ý nghĩa thống kê trên thang iADRS sau 18 tháng hay không.

Mức độ an toàn cũng sẽ là yếu tố trung tâm trong hồ sơ lợi ích - rủi ro của chương trình. Ban lãnh đạo dự báo tỷ lệ ARIA-E tổng thể ở vùng thấp của khoảng hai chữ số và có thể nhất quán giữa các kiểu gen, nhưng nghiên cứu vẫn đang được làm mù và kết quả thực tế vẫn chưa sẵn có.

Nguồn tiền mặt hiện tại chỉ kéo dài đến đầu năm 2027 theo các kế hoạch lâm sàng và vận hành hiện hành. Trong khi đó, thời gian và thiết kế của giai đoạn phát triển Phase III, việc dùng liều tiêm dưới da và các nghiên cứu lâm sàng giai đoạn đầu cho ACU-301 hoặc ACU-401 vẫn phụ thuộc vào bộ dữ liệu từ ALTITUDE-AD.

Những điểm nổi bật trong phiên Hỏi & Đáp với các chuyên gia phân tích

• Ngưỡng thành công lâm sàng: Ban lãnh đạo cho biết mức làm chậm khoảng 30% trên thang iADRS sau 18 tháng sẽ tạo cơ sở để tiếp tục phát triển sabirnetug.
• Sự khác biệt giữa các mức liều: Cả hai mức liều 35 mg/kg và 50 mg/kg đều có thể mang lại hiệu quả. Ban lãnh đạo lưu ý rằng liều 50 mg/kg có tiềm năng tạo ra tác động rõ rệt hơn trên chụp PET mảng xơ amyloid.
• Duy trì sau khi xóa bỏ mảng xơ: Acumen nhận thấy cơ sở khoa học cho việc sử dụng kháng thể chọn lọc oligomer sau khi xóa bỏ mảng xơ vì các tích tụ hòa tan có thể tiếp tục thúc đẩy bệnh lý tiến triển. Tuy nhiên, ALTITUDE-AD đang tập trung vào sabirnetug như một phương pháp điều trị chính.
• Tác động điều trị ở giai đoạn sớm hơn: Thử nghiệm bao gồm các đánh giá nhằm xác định liệu việc trung hòa các oligomer độc hại có thể tạo ra tác động ở các thời điểm sớm hơn hay không. Kết quả có thể cung cấp thông tin giúp các nghiên cứu trong tương lai xác định hoạt tính của thuốc sớm hơn.
• Phát triển thế hệ tiếp theo: Các kết quả của ALTITUDE-AD sẽ giúp định hình việc lựa chọn liều lượng, chiến lược chỉ dấu sinh học và kế hoạch lâm sàng giai đoạn đầu cho các ứng viên tăng cường phân phối vào não bộ.
• Dữ liệu bị thiếu và tỷ lệ duy trì bệnh nhân: Ban lãnh đạo cho biết tỷ lệ duy trì bệnh nhân đã vượt kỳ vọng và các dữ liệu bị thiếu sẽ được xử lý bằng các phương pháp truyền thống theo quy định trong đề cương nghiên cứu.

Toàn văn Biên bản Cuộc họp Báo cáo Kết quả Kinh doanh

Toàn văn cuộc gọi công bố kết quả kinh doanh

Phần trình bày của ban lãnh đạo

Operator

Good day, and welcome to the Acumen Pharmaceuticals Third Quarter 2026 Conference Call and Webcast. [Operator Instructions] Please note, this call may be recorded. I would now like to turn the call over to Alex Braun, Head of Investor Relations. Please go ahead.

Alex Braun

Thanks, Michelle. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended September 30, 2026. With me today are Dan O'Connell, our Chief Executive Officer; and Matt Zuga, our CFO and Chief Business Officer. They'll have a brief prepared remarks, and then we'll open the call for questions. And before we begin, we encourage listeners to go to the Investors section of the Acumen website to find our press release issued this morning that we'll discuss today.

Please note that during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans. Please see Slide 2 of our corporate presentation, our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements. We undertake no obligation to update or revise the information provided on this call or in the accompanying presentation as a result of new information or future results or developments. So, with that, I'll turn the call over to Dan.

Daniel O'Connell

Great. Thanks, Alex. Good morning, everyone, and thanks for joining us today. In the third quarter, our team has been very busy readying for the top line readout from our Phase II ALTITUDE-AD trial investigating our lead product candidate, sabirnetug. If you've been following our company for some time, you're likely well aware that these results are highly anticipated. We are testing our central scientific thesis that arresting the harm done by synaptotoxic amyloid beta oligomers in the brain may offer a differentiated approach to treating Alzheimer's disease. So, today, I'm pleased to confirm that we expect to announce these Phase II results this November.

We are confident that we are fully evaluating the A-beta oligomer hypothesis with this study. ALTITUDE-AD is a large, well-powered Phase II trial with clinically meaningful endpoints. We are testing 2 doses of sabirnetug against placebo, carefully considered based on our Phase I study in Alzheimer's patients, such that either dose may prove efficacious in the Phase II. We have executed the study to a very high operational standard with rapid enrollment, close engagement with study sites and investigators, and high rollover into the open-label extension of the study. As previously mentioned, we envision this study as part of a potential registration package and have conducted the study as such with a single confirmatory Phase III anticipated following positive Phase II results.

As previously outlined, ALTITUDE-AD was designed to detect a statistically significant difference between sabirnetug and placebo on the primary efficacy endpoint, iADRS, following 18 months of treatment. We expect the top line data set to encompass primary endpoint results, key secondary outcomes, including the CDR Sum of Boxes, safety evaluations covering adverse events and ARIA rates, and a range of informative fluid and imaging biomarkers. We believe that sabirnetug has the potential to demonstrate a differentiated benefit-to-risk profile given its unique product attributes as a selective anti-A-beta oligomer IgG2 monoclonal. We look forward to sharing the data in November.

We also continue to advance our enhanced brain delivery program, or EBD, for the treatment of Alzheimer's disease, representing the only program combining a validated blood-brain barrier penetrating technology with an A-beta oligomer selective therapeutic antibody. As a reminder, we are working on 2 candidates in the lead up to an IND filing expected in mid-2027. One candidate, ACU-301, is based on a bispecific antibody incorporating sabirnetug. And ACU-401 incorporates a novel A-beta selective antibody with differentiated properties known as ACU-234. We presented encouraging data at the AAIC meeting in July, showing that after intravenous dosing, all tested EBD bispecific antibodies achieved multifold greater brain exposure than unmodified ACU-234 alone.

ACU-401, in particular, achieved up to a 40-fold greater frontal cortex exposure in nonhuman primates and significant increase in exposures in deep brain regions. The degree of brain penetration we observed in the cynomolgus monkeys combined with the preserved soluble A-beta oligomer selectivity and a clean hematological profile exceeded our expectations and give us confidence in the differentiated potential of our EBD program. The imminent data readout for sabirnetug and the development of our next-generation EBD candidates demonstrate both the robustness of our pipeline and our ability to deliver on key priorities, positioning us for an important period of value-creating milestones ahead, both near and longer term. Again, we look forward to updating you in November. And, with that, I'll turn the call over to Matt.

Matt Zuga

Thanks, Dan. As a reminder, our third quarter 2026 financial results are available in the press release we issued this morning and in our 10-Q we will file later today. We ended the third quarter with approximately $79 million in cash and marketable securities on our balance sheet, which is expected to support our current clinical and operational activities into early 2027. R&D expenses were $21.1 million in the third quarter. The decrease over the prior year was primarily due to reductions in manufacturing and materials costs as well as CRO costs, which are both associated with our ALTITUDE-AD clinical trial.

G&A expenses were $4.7 million in the third quarter, roughly flat to the same period in the prior year. This led to a loss from operations of $25.8 million and a net loss of $25.4 million in the third quarter. We look forward to reporting on our Phase II ALTITUDE-AD study next month and remain committed to maximizing the potential of our portfolio of A-beta oligomer targeted antibodies to generate value for patients living with Alzheimer's disease, their caregivers, and our stakeholders. And, with that, we can open the call for Q&A. Operator?

Operator

[Operator Instructions] Our first question comes from Jason Zemansky with Bank of America.

Phần hỏi đáp

Jason Zemansky

Congratulations on the progress. Looking forward to the results. This may seem like a random question now. But as we think about the evolving treatment paradigm, it looks like Biogen is now positioning LEQEMBI as a follow-on after donanemab clears plaque. And the argument is that soluble species, sort of, keep driving disease after the plaque has gone. So, it seems like a natural place for an oligomer selective antibody. How do you think about sabirnetug in addition to, sort of, a primary role, but as a maintenance after plaque clearance or in combination with a plaque clearer? And could anything in the ALTITUDE-AD data set inform that?

Daniel O'Connell

Thanks, Jason. Great question. So, we've always been advocates for chronic dosing, essentially while patients are stable within an early AD stage of disease as we believe these soluble aggregates are present and persistent in driving disease pathology. So, it would be a logical extension to consider sabirnetug or an oligomer selective antibody as a post-plaque clearance follow-on. But we -- so, in the primary mode, we're focused on the primary outcome for sabirnetug in ALTITUDE-AD with an 18-month primary using the iADRS. So, I think we'll have the first case evidence is really out of that Phase II moving towards Phase III, but the therapeutic rationale for sabirnetug as a follow-on would make sense to us as we sit here today.

Operator

Our next question comes from Paul Matteis with Stifel.

Jo Yi Chudy

This is Emily on for Paul. We were just wondering if you could talk a little bit about your dose selection and what might you expect to see in this upcoming readout that would look different on efficacy and safety between those 2 doses?

Daniel O'Connell

Thanks, Emily. Yes. So, for the Phase II, we chose doses of 35 mg/kg and 50 mg/kg, and this is IV dosing every 4 weeks. So, we arrived at those doses as a consequence of the dose exposure and some of the pharmacodynamic effects we observed in the Phase I. So, a combination of the Phase I results with some dose modeling allowed us to select these 2 doses. And importantly, we think both 35 and 50 each are within the zone that could be efficacious.

It may be that the higher dose of 50 mg/kg may have perhaps more observed effects on the amyloid PET signal, but we will see how that reads out in the weeks ahead. We're getting close to that data set. So, very excited to see it. But important to establish that both of these doses, we think, are within that zone of efficacy in conjunction with the safety profile that we think could offer a benefit-to-risk profile that's attractive to patients.

Operator

Our next question comes from Pete Stavropoulos with Cantor Fitzgerald.

Pete Stavropoulos

Congrats on the execution, looking forward to the data next month. A couple for me. I'm wondering what your current thinking is in terms of the bar or what is the minimum we'd like to, sort of, see out of ALTITUDE-AD to move forward, especially since this is the first time that the oligomer hypothesis is being tested. So, the bar for both clinical scales and biomarker data. And what would we expect any OLE data in the readout?

Daniel O'Connell

Thanks, Pete. So, as you may recall, we've been guiding towards a clear clinical success of 30% slowing on the iADRS after 18 months of placebo-controlled period. We think that's a zone in which that would give us the basis for moving forward. And in terms of the safety profile, I mean, the overall adverse event profile, inclusive of ARIA rates and infusion site reactions and other elements of the safety profile that's going to be part of this top line readout. We would anticipate low double-digit ARIA-E in totality and maybe consistent across the genotypes as part of the support of the oligomer hypothesis and the grounds in which sabirnetug would be moving forward to Phase III. So, that's, kind of, how we're thinking about that.

Sorry, your second question, Pete? OLE data. So, yes, as you are good to point out, our open-label extension is a 12-month open-label extension. We've had high rollover. Essentially greater than 95% of people eligible to participate in the open-label extension have elected and consented to do so. That portion of the study will be reading out over an extended period of time. We do think that, that will generate evidence into 2027 and likely won't be part of the top line results. I think important to establish, however, the top line results, as I just mentioned on the scripted call, will be inclusive of the primary and secondary, both efficacy and safety and include biomarker effects, both imaging and fluid.

In terms of the -- we'll be looking at the amyloid PET as a conventional imaging measure. We'll also be looking at fluid biomarkers, CSF and plasma. I think we'll principally be looking at things such as the p-tau217 as a measure of disease status, potentially progression. And I think that's going to be a complete data set to inform stakeholders on the merits of sabirnetug and provide evidence in support of the oligomer hypothesis.

Pete Stavropoulos

All right. And just a question on EBD. How are you thinking about the other path forward for ACU-301 or 401, the MAD/SAD studies? Are you going to go straight into patients or healthy volunteers first and the length of time you, sort of, aim to have patients on the -- in the MAD study? And what optionality do these candidates offer?

Daniel O'Connell

Yes. Thanks, Pete. Well, yes, so, we think there's a lot of optionality in our EBD program. And I think having both 301 and 401 in the mix is really helpful because it affords us a bit of diversity in terms of the profiles and ways to move the program forward. I think we've learned so much in the development of sabirnetug, both initially with INTERCEPT, which was our Phase I study exclusively in Alzheimer's patients that gave us really solid Phase I proof of mechanism data in support of sabirnetug and that, of course, as I just mentioned, informed dosing strategy and the plan for Phase II.

I think the team is still working on refining precisely what we want to do with EBD in the early phase and translational studies. And we'll be looking at the ALTITUDE results, in particular, to assess dosing strategy as well as biomarker strategy for the EBD program. So, we think one of the advantages we at Acumen have is all of the experience we've undertaken with sabirnetug not only through Phase I, but through a robust Phase II, that really serves as a foundation for our strategy for developing the EBD candidates.

Pete Stavropoulos

Congrats on the progress once again.

Operator

Our next question comes from Tom Shrader with BTIG.

Thomas Shrader

I guess we'll all hold our breath for 30 days. But I think one of the interesting things about sabirnetug is that it might act faster given the monomer binding, things like that. And the question is, how set up are you to capture that? When are you looking at patients? When are you scanning? When are you taking soluble biomarkers? I think a fantastic readout from this might be that your next Phase III could be shorter because the drug works faster. And the question is, how set up are you to catch some sort of readout like that?

Daniel O'Connell

Thanks, Tom. So, with sabirnetug's high selectivity for toxic A-beta oligomers, we do hear the thesis holds that neutralizing those toxic species early in the early course of disease could have not only a slowing of disease, but some other potentially, sort of, symptomatic benefit. I think that's an interesting possibility. I do know that our plans have incorporated elements of observing or essentially capturing that possibility.

So, I think we will know a lot in the coming weeks as the ALTITUDE reads out as to whether, given the mechanism, there is a potential to look at earlier time points for establishing a drug effect going forward. So, yes, it's a really -- as you mentioned, we think ALTITUDE is a robust test of this central scientific hypothesis and are eagerly awaiting the unblinding and the interpretation of those results.

Operator

Our next question comes from Geoff Meacham with Citi.

Mary McKeown

This is Mary Keown on for Geoff. Could you speak to some of the KOL feedback you're receiving on sabirnetug and the ALTITUDE-AD program? Maybe what are physicians looking for in a treatment? And how could sabirnetug address these needs? And then just as another one, maybe what feedback do they have on the mechanism here as well?

Daniel O'Connell

Great. So, in our travels and interactions with KOLs, I mean, they're mostly principally focused on better treatment options for patients. And I think as such, sabirnetug, with a different mechanism, not a plaque-busting agent, but rather something that targets these soluble toxic species, is something of high interest and given that potential.

So, they are keenly -- as is everybody in the field, I think, kind of, looking at ALTITUDE as a differentiated study where sabirnetug could shift some people's thinking on what the primary mode of treatment should be, whether it be oligomers versus plaque and so forth. So, we think there's a lot of anticipation going into next month's readout. And we do think that the study has a mix of data outcomes and readouts that will be very informative as to the merits of sabirnetug and underpin the attractiveness of targeting toxic oligomers in a primary, selective and direct fashion.

Operator

Our next question comes from Dev Prasad with Lucid Capital Markets.

Dev Prasad

Congrats on the progress. A couple of questions. One is, as we approach the readout, can you comment on patient retention? And maybe how should we think about the impact of missing data or discontinuation on primary efficacy analysis? And another one is on subcutaneous. I believe the subcu work was on hold until the dosage chosen. So, wondering, do you plan to initiate that work after the Phase II trial?

Daniel O'Connell

Thanks, Dev. So, in terms of retention in the primary ALTITUDE-AD study, as we mentioned, we've conducted the study to a very high standard. We have -- our retention within the primary portion of the study has exceeded, sort of, our expectations, which is great, and we've had high rollover into the open-label extension. So, just objectively, we think people that are participating in the study like the study and have been inclined to stay in and/or extend their involvement in the study. So, that's encouraging. And yet it's obviously still blinded data.

In respect to your question on missing data, I think we will be addressing those issues in a, kind of, conventional and per protocol basis. So, I don't know that there's more I can offer -- more specifics I can offer on that question.

And thirdly, in terms of the subcu, yes, we completed a healthy volunteer, essentially a bioavailability study back that read out in early '25. We think we have what we need in terms of the contrast between IV dosing, subcutaneous dosing of the sabirnetug formulation. We anticipate using the Phase III in one direction or another to incorporate a subcutaneous advancement. And I think you can look at some predicates out there, if you look at what Eisai and Biogen did with LEQEMBI, incorporating the subcu as part of the open-label extension in Phase III, that could be analogous to how we would be moving forward in the future with a subcutaneous option.

Operator

This concludes the question-and-answer session. Thank you for your participation. You may now disconnect. Good day.