Acumen Pharmaceuticals Inc (ABOS) 2026 Q2 法說會逐字稿

Good day, and welcome to the Acumen Pharmaceuticals second-quarter 2026 conference call and webcast. At this time, all participants are in listen-only mode. (Operator Instructions) Please note this call is being recorded.

大家好，歡迎收聽 Acumen Pharmaceuticals 2026 年第二季財報電話會議與網路直播。目前所有與會者皆為只聽模式。(接線員指示) 請注意，本通話將被錄音。

I'll now turn the call over to Alex Braun, Head of Investor Relations. Please go ahead.

現在我將把電話交給投資人關係主管 Alex Braun。請開始。

Thanks, Michelle. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended June 30, 2026.

謝謝你，Michelle。各位早安，歡迎參加 Acumen 的電話會議，討論截至 2026 年 6 月 30 日止季度的業務更新與財務結果。

With me today are Dan O'Connell, our Chief Executive Officer; and Matt Zuga, our CFO and Chief Business Officer. They will have brief prepared remarks and then we'll open the call for questions. Joining for the Q&A session, we also have Dr. Jim Doherty, our President and Chief Development Officer; and Dr. Eric Siemers, our Chief Medical Officer.

今天與我一同出席的有我們的執行長 Dan O'Connell，以及我們的財務長兼首席商務長 Matt Zuga。他們將先做簡短的準備發言，之後我們會開放提問。在問答環節，我們也邀請到總裁兼首席開發長 Jim Doherty 醫師，以及首席醫療長 Eric Siemers 醫師。

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.

在開始之前，我們建議聽眾前往 Acumen 官網的投資人專區，查閱我們今天早上發布、並將於今日討論的新聞稿。請注意，在今天的電話會議中，我們可能會在聯邦證券法所界定的範圍內作出前瞻性陳述，包括關於我們的財務展望與預期業務計畫的陳述。

Please see slide two 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.

請參閱我們公司簡報的第 2 張投影片、今天早上發布的新聞稿，以及我們最近向美國證券交易委員會（SEC）提交的年度與季度報告，其中載有重要風險因素，可能導致實際結果與前瞻性陳述中明示或暗示者存在重大差異。除非因新資訊或未來結果或發展所致，我們不承擔更新或修訂本通話或隨附簡報中所提供資訊的任何義務。

So with that, I'll turn the call over to Dan.

那麼，接下來我把電話交給 Dan。

Great. Thanks, Alex. Good morning, everyone, and thanks for joining us today.

好的。謝謝你，Alex。各位早安，感謝今天加入我們。

During the second quarter, our focus remained on disciplined execution as we advanced sabirnetug toward the highly anticipated top-line readout from our Phase 2 ALTITUDE-AD trial, which we continue to expect late this year. We believe this will be an important efficacy readout in the Alzheimer's field.

在第二季期間，我們的重點仍放在嚴謹執行，推進 sabirnetug，朝向備受期待的第二期 ALTITUDE-AD 試驗主要結果（top-line）讀出；我們仍預期將於今年稍晚公布。我們相信這將是阿茲海默症領域一項重要的療效讀出。

ALTITUDE-AD remains a critical test of our central scientific thesis that selectively targeting synaptotoxic amyloid beta oligomers may offer a differentiated approach to treating Alzheimer's disease. A substantial body of evidence support this hypothesis, and we're excited by the opportunity to evaluate that thesis in a well-powered randomized Phase 2 study with clinically meaningful endpoints.

ALTITUDE-AD 仍是對我們核心科學論點的關鍵檢驗：選擇性鎖定具突觸毒性的類澱粉蛋白 β（amyloid beta）寡聚體，可能提供治療阿茲海默症的差異化途徑。大量證據支持此一假說，我們也很期待能在一項具足夠統計效力的隨機第二期研究中，以具臨床意義的終點來評估該論點。

Our Phase 2 results have the potential to substantially expand on our Phase 1 results, which include a demonstration of A-beta oligomer target engagement and biomarker changes that we're seeing as early as three months of treatment as we previously reported.

我們的第二期結果有潛力在第一期結果的基礎上大幅延伸；第一期結果包括我們先前所報告的 A-β 寡聚體靶點結合（target engagement）證據，以及在治療早至三個月即觀察到的生物標記變化。

We continue to be encouraged with the engagement of patients, caregivers, investigators, and study sites participating in ALTITUDE-AD, as well as in its 12-month open-label extension study. Their commitment has been instrumental in bringing us to this important inflection point.

我們持續對 ALTITUDE-AD 以及其 12 個月開放標籤延伸研究中，病患、照護者、研究人員與試驗中心的投入感到鼓舞。他們的承諾對於推動我們走到這個重要的轉折點至關重要。

I believe the strong relationships the Acumen team holds with study sites and investigators is particularly supported by Acumen's patient-centric approach. At AAIC last month in London, we presented patient experience data collected from participants and study partners prior to treatment in ALTITUDE-AD.

我認為 Acumen 團隊與試驗中心及研究人員之間的強健關係，特別得益於 Acumen 以病患為中心的作法。在上個月於倫敦舉行的 AAIC 會議上，我們發表了在 ALTITUDE-AD 治療前，向受試者與研究夥伴蒐集的病患體驗資料。

Results illustrate the diverse ways individuals with early Alzheimer's disease experience respond to and cope with cognitive and functional changes, underscoring the importance of capturing patient experience directly to better understand the meaningful benefit at this stage of disease.

結果顯示，早期阿茲海默症患者在面對、回應並因應認知與功能變化時，存在多樣化的方式；這凸顯了直接蒐集病患體驗的重要性，以更好理解在此疾病階段何謂具意義的效益。

As we've previously described, ALTITUDE-AD was designed to detect a statistically significant difference on its primary clinical efficacy endpoint, iADRS, after 18 months of treatment with sabirnetug compared with Placebo. We expect the top-line data set to include results from the primary endpoint, key secondary measures such as the CDR-SB, safety assessments including adverse events and iADRS, as well as important fluid and imaging biomarkers.

如我們先前所述，ALTITUDE-AD 的設計目標是在以 sabirnetug 治療 18 個月後，相較於安慰劑，在其主要臨床療效終點 iADRS 上偵測到具統計顯著性的差異。我們預期主要結果資料集將包含主要終點結果、關鍵次要指標（如 CDR-SB）、安全性評估（包括不良事件與 iADRS），以及重要的體液與影像生物標記。

The study is evaluating two dose levels, 35 milligrams per kilogram and 50 milligrams per kilogram compared with placebo. Both these dose levels are within the exposure range previously shown to achieve pharmacodynamic target engagement.

本研究評估兩個劑量水準：每公斤 35 毫克與每公斤 50 毫克，並與安慰劑比較。這兩個劑量水準皆落在先前已證實可達成藥效學靶點結合的暴露範圍內。

While we remain focused on execution and preparation for the readout, enthusiasm across the organization continues to build as we approach this landmark catalyst. We believe that sabirnetug has the potential to differentiate to demonstrate a differentiated benefit-to-risk profile given its unique product attributes as an anti-A-beta oligomer IgG2 monoclonal. We look forward to sharing the results later this year.

在我們持續專注於執行與為讀出做準備的同時，隨著我們接近這項里程碑式的催化事件，整個組織的熱度也持續升溫。我們相信，鑑於 sabirnetug 作為抗 A-β 寡聚體 IgG2 單株抗體的獨特產品特性，其有潛力展現差異化的效益風險（benefit-to-risk）概況。我們期待在今年稍晚分享結果。

In the second quarter, we announced the nomination of two Enhanced Brain Delivery candidates for the treatment of Alzheimer's disease, representing the only program combining a validated blood-brain barrier penetrating technology with an anti A-beta oligomer-selected therapeutic antibody.

在第二季，我們宣布提名兩項用於治療阿茲海默症的增強腦部遞送（Enhanced Brain Delivery, EBD）候選藥物；這是唯一一個將已驗證的血腦障壁穿透技術與抗 A-β 寡聚體選擇性治療抗體結合的計畫。

Building on robust preclinical data from both in vitro and in vivo studies, we exercised our option with JCR Pharmaceuticals and will advance two candidates, ACU301 and ACU401. ACU301 is a bispecific antibody incorporating sabirnetug and ACU401 incorporates a novel next-generation A-beta oligomers-selective antibody with differentiated properties. This is known as ACU234.

基於來自體外與體內研究的強勁臨床前資料，我們行使與 JCR Pharmaceuticals 的選擇權，並將推進兩個候選項目 ACU301 與 ACU401。ACU301 是一種雙特異性抗體，結合 sabirnetug；ACU401 則納入一種具差異化特性的全新次世代 A-β 寡聚體選擇性抗體。該抗體稱為 ACU234。

We view our EBD program as extending the optionality in our pipeline and will continue to evaluate both candidates in the lead up to support a filing of an IND. Confirming our mouse data in non-human primates is a pivotal step in this work.

我們認為 EBD 計畫可提升我們產品線的選擇性（optionality），並將持續在推進至支持提交 IND 的過程中評估這兩個候選項目。在非人靈長類中確認我們的小鼠資料，是此項工作中的關鍵一步。

At last month's AAIC conference, we presented data showing that after intravenous dosing, all three EBD bispecific antibodies achieved greater brain exposure than unmodified ACU234 alone. ACU401, in particular, achieved up to a 40-fold greater frontal cortex exposure in non-human primates and significant increase in exposures in deep brain regions.

在上個月的 AAIC 會議上，我們發表的資料顯示，在靜脈給藥後，三種 EBD 雙特異性抗體的腦部暴露量皆高於未修飾的 ACU234 單獨使用。其中 ACU401 尤其在非人靈長類中，額葉皮質暴露量最高可提升至 40 倍，且在深部腦區的暴露量亦顯著增加。

The degree of brain penetration reserved in cynomolgus monkeys combined with preserved soluble A-beta oligomer selectivity and a clean hematological profile exceeded our expectations and gives us confidence in the differentiated potential of our EBD program's approach. We continue to anticipate an IND filing for our lead EBD candidate in mid-2027.

在食蟹猴中觀察到的腦部穿透程度，加上可溶性 A-β 寡聚體選擇性得以保留，以及乾淨的血液學特徵，均超出我們的預期，並使我們對 EBD 計畫方法的差異化潛力更具信心。我們仍預期將於 2027 年年中為我們的領先 EBD 候選項目提交 IND。

Coming up, I'd like to flag for investors in anticipating virtual Investor Relations Day to be held on September 16. Please mark your calendars to view live or as a recording as we hope this will be a helpful review for the Acumen investment thesis prior to ALTITUDE's Phase 2 data readout.

接下來，我想提醒投資人，我們預計於 9 月 16 日舉辦線上投資人關係日。請在行事曆上標記日期，屆時可觀看直播或回放；我們希望這將有助於在 ALTITUDE 第二期資料讀出之前，回顧 Acumen 的投資論點。

The events of sabirnetug in our next generation blood-brain barrier EBD candidates underscores the strength of both our scientific platform and our ability to execute, positioning us well for a significant eventful remainder of 2026. I look forward to updating you on our EBD program and on our Phase 2 results for sabirnetug late this year.

sabirnetug 的進展以及我們次世代血腦障壁 EBD 候選項目的推進，凸顯了我們科學平台的實力與執行能力，使我們在 2026 年剩餘期間迎接多項重要里程碑時具備良好定位。我期待在今年稍晚向各位更新我們的 EBD 計畫，以及 sabirnetug 的第二期結果。

And with that, I'll turn the call over to Matt.

接下來，我把電話交給 Matt。

Thank you, Dan. As a reminder, our second-quarter 2026 financial results are available in the press release we issued this morning and in our 10-Q we will file later today.

謝謝你，Dan。提醒各位，我們 2026 年第二季財務結果已載於我們今天早上發布的新聞稿中，並將於今日稍晚提交的 10-Q 中揭露。

We ended the second quarter with $110.2 million in cash and marketable securities on our balance sheet, which is expected to support our current clinical and operational activities into early 2027.

截至第二季末，我們資產負債表上的現金與有價證券為 1.102 億美元，預期可支應我們目前的臨床與營運活動至 2027 年初。

R&D expenses were $27.8 million in the second quarter. The decrease over the prior year was primarily due to reductions in manufacturing and materials costs as well as CRO costs as we get into the final leg of our clinical trial.

第二季研發費用為2,780萬美元。較去年同期下降主要是因為隨著我們進入臨床試驗的最後階段，製造與材料成本以及CRO成本均有所降低。

G&A expenses were $4.7 million in the second quarter, roughly flat for the same period in the prior year. This led to a loss from operations of $32.6 million and a net loss of $32.7 million in the second quarter.

第二季一般及行政（G&A）費用為470萬美元，與去年同期大致持平。因此，第二季營運虧損為3,260萬美元，淨虧損為3,270萬美元。

We are confident in our scientific innovation and strong track record of execution as we work toward our Phase 2 ALTITUDE-AD readout later this year and advance our EBD program. We remain dedicated to building value with our portfolio of A-beta oligomer-targeted antibodies for Alzheimer's patients, caregivers, and stakeholders.

在我們朝向今年稍晚公布第二期ALTITUDE-AD試驗結果並推進EBD計畫之際，我們對自身的科學創新與強勁的執行紀錄充滿信心。我們仍致力於透過我們針對Aβ寡聚體的抗體產品組合，為阿茲海默症患者、照護者與利害關係人創造價值。

And with that, you can open the call for Q&A. Operator?

接下來可以開放問答。接線員？

(Operator Instructions)

（接線員指示）

Paul Matteis, Stifel.

Paul Matteis，Stifel。

I guess another company doing an oligomer-specific approach read out some blinded data recently. Maybe, can you talk about like what are the differences between their approach versus yours and trial design? And how much can we read through on their clean safety to your upcoming data? Thank you so much.

我想最近有另一家公司採用寡聚體特異性策略，讀出了部分盲態資料。也許你們能談談他們的方法與你們的方法及試驗設計之間有哪些差異？另外，他們乾淨的安全性結果，對你們即將公布的資料有多少可供類推的意義？非常感謝。

Yeah, we saw the announcement of the blinded interim assessment. This is really early-stage status, and there's not too much we can conclude from that reporting or that announcement. And we'll be interested to see how that study reads out sometime early next year. We reported Phase 1 results in 2023, which, to our view, established a really robust clinical target engagement of A-beta oligomers.

是的，我們看到了那項盲態期中評估的公告。目前仍屬非常早期階段，從該報導或公告中我們能下的結論不多。我們也會關注該研究在明年年初左右的讀出結果。我們在2023年公布了第一期結果；依我們的看法，該結果確立了對Aβ寡聚體非常扎實的臨床靶點結合（target engagement）。

And with just three doses in that Phase 1 study, we're seeing both effects on both fluid and imaging biomarkers that exceeded our expectations and underpin our confidence in why in a large study, in an efficacy-based study, such as ALTITUDE-AD, sabirnetug is positioned for success.

而且在那項第一期研究中僅給予三次劑量，我們就觀察到體液與影像生物標記皆出現效果，且超出我們的預期；這也支撐了我們的信心：在像ALTITUDE-AD這樣的大型、以療效為導向的研究中，sabirnetug具備成功的條件。

Okay, thank you so much. And maybe a quick follow-up. In the selection of your EBD candidates, what were the parameters that you thought to optimize? And where do you think the second molecule might be better than the bispecific sabirnetug? Thank you so much.

好的，非常感謝。再追問一個簡短問題。在你們選擇EBD候選分子時，你們認為需要最佳化的參數有哪些？你們認為第二個分子在哪些方面可能優於雙特異性sabirnetug？非常感謝。

Thanks. I can quickly comment on that. I think for our EBD program, we envision from a product profile standpoint, subcutaneous administration as a convenient form for delivery as well as preserving the oligomer selectivity, potentially enhancing that selectivity and an efficient transport across the blood-brain barrier using the transparent carrier technology as partner with JCR.

謝謝。我可以簡單回應。就我們的EBD計畫而言，從產品特性（product profile）的角度，我們設想以皮下注射作為便利的給藥方式，同時保留對寡聚體的選擇性，並可能進一步提升該選擇性；此外，透過與JCR合作的透明載體技術（transparent carrier technology），有效穿越血腦屏障。

So I think we're looking at safety, efficacy, and broader exposure in a format that would lend itself to convenient sub-Q dosing. So both of the candidates have at least so far demonstrated all of those attributes and some of that data has been presented at meetings, and we'll continue to report on findings in that program as we march toward an IND filing on a lead sometime in mid-27.

因此，我們著眼於在一種有利於便利皮下（sub-Q）給藥的形式下，兼顧安全性、有效性與更廣泛的暴露。到目前為止，兩個候選分子都已展現上述特性，其中部分資料也已在會議上發表；隨著我們朝向在2027年年中左右就領先候選分子提交IND，我們也會持續更新該計畫的研究發現。

And Matthew, this is Jim. Maybe I can add a little bit to what Dan has been saying. Of course, when you see the candidates that we announced, those represent the sort of culmination of a process. And we had a really robust collaboration with JCR. And what it allowed us to do is really look at a bunch of different parameters for optimizing for the right fit to match the carrier and the cargo to come up with the final product.

Matthew，我是Jim。也許我可以補充Dan剛才所說的一點。當然，當你看到我們公布的候選分子時，那些其實是整個流程的階段性成果。我們與JCR有非常扎實的合作。這讓我們能夠檢視許多不同的參數，去最佳化「合適的匹配」，把載體與貨物（carrier與cargo）配對，最終形成成品。

And so, we looked at a number of things. We looked at affinity for TfR, we looked at valency, monovalent versus divalent. We looked at a bunch of parameters around the potential risk for anemia and things like that. And so, it really represents the culmination of a whole campaign to optimize for what we think is the best fit to deliver these oligomer-targeting antibodies into the CNS.

因此，我們評估了多項因素。我們看了對TfR的親和力，也看了價數（valency），例如單價與雙價。我們也檢視了多個與貧血等潛在風險相關的參數。所以，這些候選分子代表的是一整個最佳化專案的成果，我們認為這是將這些靶向寡聚體的抗體遞送進入中樞神經系統（CNS）的最佳匹配。

Jason Zemansky, Bank of America.

Jason Zemansky，美國銀行（Bank of America）。

You described ALTITUDE, I guess, is designed to detect a statistic difference in iADRS, but with two active doses, can you clarify the framework and whether each dose is independently powered against a placebo? If only one succeeds, under what circumstances would constitute a statistically robust positive study? And then a quick follow-up, please. Thanks.

你們提到ALTITUDE的設計應該是用來偵測iADRS上的統計差異；但由於有兩個有效劑量組，能否釐清其架構，以及每個劑量是否各自相對於安慰劑具備獨立的統計檢定力（powered）？如果只有一個劑量成功，在什麼情況下會構成一項在統計上穩健的陽性研究？然後我還有一個簡短追問。謝謝。

Thanks, Jason. Good question. As we have not specifically provided details on the powering and the analysis. So I think, I don't know that we can go into greater detail on that this morning. Yes, we do have both doses, both of which have demonstrated target engagement. We think both of these doses could emerge as efficacious doses. And we'll be looking forward to providing more information as we get closer to the data readout late this year.

謝謝，Jason。問得很好。由於我們尚未具體提供關於檢定力設定與分析方法的細節，所以我想今天早上我們不便再進一步深入說明。是的，我們確實有兩個劑量，而且兩者都已顯示靶點結合。我們認為這兩個劑量都有可能成為具療效的劑量。隨著我們接近今年稍晚的資料讀出，我們也期待能提供更多資訊。

Got it. And then maybe without getting too much into the efficacy bar, can you speak to the work you're doing now to minimize the interval between the Phase 2 results and the initiation of a Phase 3? Any regulatory engagement, CMC, partner discussions, site planning, which activities are gated until the data?

了解。那麼在不過度談論療效門檻的前提下，你們能否談談目前正在做哪些工作，以縮短第二期結果與啟動第三期之間的時間間隔？例如法規互動、CMC、合作夥伴討論、試驗中心規劃等；哪些活動會等到資料出來才會啟動（gated）？

Well, you can imagine there are elements of everything that you mentioned that are ongoing now, with the exception perhaps of regulatory interactions in terms of establishing the Phase 3 design and so forth. But there's a lot of activity and anticipation to minimizing the white space.

如你所想，你提到的各個面向目前都有一些工作在進行中；或許例外的是，與確立第三期設計等相關的法規互動。但我們確實有大量活動在推進，也在預先規劃，以盡量縮小中間的空窗期。

And we're hopeful for a successful readout in ALTITUDE that really will help facilitate and accelerate our ability to move sabirnetug into a single pivotal Phase 3.

我們也希望ALTITUDE能成功讀出，這將有助於促進並加速我們把sabirnetug推進到單一關鍵性第三期試驗的能力。

Pete Stavropoulos, Cantor Fitzgerald.

Pete Stavropoulos，Cantor Fitzgerald。

My first question is, there are biomarker data that suggests certain tau fragments like p-tau217 can be used as a marker for amyloid pathology while markers like MTBR-tau243 identifies tau tangle pathology in Alzheimer's disease.

我的第一個問題是，有一些生物標記資料顯示，某些tau片段（例如p-tau217）可作為類澱粉樣病理的指標，而像MTBR-tau243這類標記則可辨識阿茲海默症中的tau纏結病理。

I know that you've incorporated and will look at p-tau217 in the altitude study, but can you talk about tau243? Do you plan to look at it in altitude? And how could you incorporate it into a Phase 3? Can it be leveraged to help or expedite patient function?

我知道你們已在ALTITUDE研究中納入並將觀察p-tau217，但能否談談tau243？你們是否計畫在ALTITUDE中觀察它？以及在第三期中要如何納入？它是否能被用來協助或加速患者功能方面的評估？

(multiple speakers)

（多位講者）

Go ahead, Eric.

Eric，你先請。

Yeah, so this is Eric Siemers. Maybe I can take that one. So yeah, the biomarker world in Alzheimer's is moving really quickly, especially with regard to blood-based biomarkers. As I think, you probably know, we use p-tau217 as part of our screening procedure actually for enrollment people into ALTITUDE, but it'll also be an outcome measure that we'll look at after we're unblinded at the end of the study.

好的，我是Eric Siemers。也許我來回答這題。是的，阿茲海默症的生物標記領域進展非常快，特別是血液型生物標記。如你可能知道的，我們在篩選流程中實際上就使用p-tau217，作為將受試者納入ALTITUDE的部分條件；同時，它也會是研究結束解盲後我們將評估的結果指標之一。

MTBR is relatively newer, and so it really wasn't being discussed at the time we designed ALTITUDE. But one of the things that we have talked about is that we have a large number of patients and lot of actually plasma samples that will be stored. And so, we have the opportunity to look at things like MTBR, new biomarkers that, especially the blood-based biomarkers that become interesting after we actually complete the study.

MTBR相對較新，因此在我們設計ALTITUDE時，相關討論還不多。但我們談到的一點是：我們有大量受試者，也會保存許多血漿樣本。因此，在研究完成之後，我們有機會去檢視像MTBR這樣的新型生物標記，特別是那些在事後變得更具意義的血液型生物標記。

So yeah, MTBR is one of the things we talk about. But I think it's not just that, it's any other new blood-based biomarker that may look interesting, we'll have the opportunity to look at.

所以是的，MTBR 是我們會討論的事項之一。但我認為不僅如此，任何其他看起來有意思的新型血液型生物標記，我們也都會有機會去評估。

And Samantha, this is Jim. Maybe just to add a little bit onto what Eric is saying. I think he's totally right that it's really an exciting time in the field for looking at these fluid-based biomarkers. And the reason for that is it really provides a lot of information about patients. And so, I think what we're seeing is people are beginning to measure these multiple markers in a lot of different studies, looking at a lot of different things.

Samantha，我是 Jim。我想在 Eric 所說的基礎上再補充一點。我認為他完全正確，現在確實是評估這些體液型生物標記的一個非常令人振奮的時期。原因在於，這些標記確實能提供大量關於病患的資訊。因此，我們看到的是，人們開始在許多不同研究中測量多種標記，並觀察許多不同面向。

It potentially gives you the opportunity to look at where a person is in their progression with disease. It has the ultimate potential, I think, to start identifying patients who might be better candidates than others. I think we're too early days for those kinds of applications, but I do think that's where the field is going.

這可能讓你有機會了解一個人在疾病進展中的位置。我認為它最終也有潛力開始辨識哪些病患可能比其他人更適合作為候選對象。我認為就這類應用而言，我們還處於非常早期的階段，但我確實認為這就是這個領域的發展方向。

And so, what we'll do, exactly as Eric is saying, as we go along, we'll continue to monitor all this. We'll use these tools as we can in our trials and we have the opportunity to go back and measure some of these things even in a post-hoc fashion. So I think this is going to continue to be an important part of Alzheimer's trials moving forward.

因此，正如 Eric 所說，隨著我們推進，我們會持續監測這一切。我們會在試驗中盡可能使用這些工具，而且我們也有機會在事後（post-hoc）回頭去測量其中一些項目。所以我認為，這將會在未來持續成為阿茲海默症試驗的重要組成部分。

Awesome. Thank you so much. And just one quick follow-up. In July, there was an announcement of a collaboration with Unlearn utilizing digital twins. Can you help us understand what this tool is and how it's incorporated into the Phase 2? And how can you possibly leverage it for Phase 3? Thank you.

太棒了。非常感謝。再追問一個很快的問題。7 月曾宣布與 Unlearn 合作，使用數位分身（digital twins）。你們能幫我們理解這個工具是什麼，以及它如何納入第二期試驗嗎？以及你們可能如何在第三期加以運用？謝謝。

Yeah, absolutely. This is Jim again. I'm happy to take that one. As you say, we have partnered with a company called Unlearn AI to use these digital twins and we see it again as another tool, another emerging tool that potentially provides some value. (technical difficulty)

好的，當然可以。我又是 Jim。我很樂意回答這題。如你所說，我們與一家名為 Unlearn AI 的公司合作使用這些數位分身；我們也把它視為另一項工具、另一項新興工具，可能帶來一些價值。（技術問題）

These are almost individualized digital models relying on the data from thousands and thousands of patients who have been studied for the progression of their disease in clinical trials and in other formats. And so, at this point, there's a tremendous amount of data about how disease progresses over time. And of course, it's incredibly complex and differentiated patient to patient.

這些幾乎是個人化的數位模型，依賴於數以千計、數以萬計病患的資料；這些病患在臨床試驗及其他形式的研究中被追蹤其疾病進展。因此，到目前為止，關於疾病如何隨時間進展，已累積了大量資料。當然，這非常複雜，而且不同病患之間差異很大。

But what these tools do is allow for using baseline data to predict how their individual course of disease will progress over time. It's a model, and I think there have to be lots of questions about how robust the models are, what you can say about them, what you can't say about them.

但這些工具所做的是，允許使用基線資料來預測個別病患的疾病歷程將如何隨時間推進。這是一個模型；我認為必然會有很多問題，例如模型有多穩健、哪些結論可以下、哪些不能下。

But potentially, they have the opportunity to do things like allow you to refine your patient selection. They have the opportunity to do things like be used as a prognostic covariate in analyses following trials. And I think a number of potential applications. But honestly, the only way to really evaluate how much value these things have is to begin to get in there and work with it yourself.

但它們可能有機會做到一些事情，例如協助你精煉病患篩選。它們也可能有機會在試驗後續分析中作為預後協變數（prognostic covariate）使用。我認為還有許多潛在應用。但老實說，真正評估這些工具有多少價值的唯一方法，就是開始親自深入使用並與之合作。

And so, that's effectively what we're doing. We're using this at this point as an exploratory endpoint. We're trying to understand how these tools might be useful to us in the future. And I think, as I was saying, there are several potential ways they can be used. So that's what our evaluation will be to understand which ones are the best ways to apply the technology for Acumen.

因此，這基本上就是我們正在做的事。我們目前把它作為探索性終點（exploratory endpoint）來使用。我們試著了解這些工具未來可能如何對我們有用。而且如我所說，它們有幾種潛在的使用方式。所以我們的評估將是要了解，對 Acumen 而言，哪些才是應用這項技術的最佳方式。

Tom Shrader, BTIG.

Tom Shrader，BTIG。

A little background or next steps on the EBD franchise? Do you anticipate you would take both candidates into humans? Do you have to start with healthy volunteers? And any sense of how many patients or people you would need to get a read on anemia?Thanks.

想請教一下 EBD 產品線的背景或下一步？你們預期會把兩個候選藥物都推進到人體試驗嗎？是否必須先從健康受試者開始？以及你們對於需要多少病患或受試者才能讀出貧血訊號，有沒有概念？謝謝。

Thanks, Tom. Jim, why don't you take that one as well?

謝謝你，Tom。Jim，要不要也請你回答這題？

Yeah, happy to. Some great questions, Tom. These are things that the team is actively working on at this point.

好的，很樂意。問題很棒，Tom。這些都是團隊目前正在積極推進的事項。

So the first question, we have identified and nominated two candidates, ACU401 and ACU301. We're doing work on both molecules, and it really is intended to identify which one offers what we think is the best overall profile. So what we would intend to do is move into clinical development with one molecule, and that will be the one that we think offers the best of possible profiles.

先回答第一個問題：我們已經辨識並提名了兩個候選藥物，ACU401 與 ACU301。我們正在對兩個分子都進行工作，目的確實是要找出哪一個能提供我們認為整體最佳的特性組合。因此，我們的意圖是以其中一個分子進入臨床開發，而那將是我們認為具備最佳可能特性組合的那一個。

As far as additional work that we're doing, there's a tremendous amount of work on CMC and tox study preparation in preparation for our plan to file an IND in mid-2027. And I think we're still working on study design. There's a lot of active discussion around it. We've got a lot of experience from the INTERCEPT study. with sabirnetug, that is going to help us identify what's exactly the best trial design to use.

至於我們正在做的其他工作，在我們計畫於 2027 年年中提交 IND 的準備過程中，CMC 與毒理研究（tox）準備方面有大量工作要做。而且我想我們仍在研究試驗設計。目前有很多積極的討論。我們從 INTERCEPT 研究（使用 sabirnetug）累積了很多經驗，這將幫助我們判斷究竟採用什麼試驗設計才是最佳。

I think what I could say at this point is really going to come down to what's the most efficient design. We are going to try to get as much information as we can as we did in the INTERCEPT study. But we also wanted to move this exciting program forward as quickly as we can. So more details later on what those design choices are going to turn out to be.

我想目前我能說的是，最終會取決於什麼是最有效率的設計。我們會像在 INTERCEPT 研究中一樣，盡可能取得最多資訊。但我們也希望盡可能快速推進這個令人振奮的計畫。因此，關於這些設計選擇最後會如何定案，之後再提供更多細節。

But I can tell you there's a lot of active discussion right now with the program team trying to lend what is going to be the most efficient design.

但我可以告訴你，目前計畫團隊正在非常積極地討論，試圖找出最有效率的設計會是什麼。

And are you going to start in healthy volunteers or are you not saying?

那你們會從健康受試者開始嗎？還是你們不方便說？

So that's one of the things that we're going to see. I think the goal is to transition to patients as quickly as we think is practical, because you get a lot of valuable information from patients, didn't intercept. But I think, exactly when that would be is honestly one of the things that we're still talking about. So yeah, I just -- we haven't really made a final decision yet.

所以這也是我們將要評估的事情之一。我認為目標是，在我們認為可行的情況下，盡快轉到病患身上，因為你能從病患獲得很多有價值的資訊，就像在 INTERCEPT 中一樣。但我認為，具體何時轉換，老實說仍是我們正在討論的事項之一。所以是的，我只是——我們還沒有做出最終決定。

And one quick one for Dan. Do you expect to go radio silent at some point? And any guidance about when?

再給 Dan 一個快問。你們是否預期在某個時間點會進入「不再對外發聲」的狀態？以及大概什麼時候？

So Tom, we continue to be convinced we'll have the top-line results for ALTITUDE-AD late '26, consistent with our guiding for some time now. We have, as I mentioned on the call, we'll have an Investor Relations Day September 16, and that'll be a forward-looking, public-facing discussion. We anticipate participating in some of the early fall activities.

Tom，我們仍然相信 ALTITUDE-AD 的主要結果（top-line results）會在 2026 年底出爐，這與我們一段時間以來的指引一致。如我在電話會議中提到的，我們將在 9 月 16 日舉辦投資人關係日（Investor Relations Day），那將是一場面向未來、對外公開的討論。我們也預期會參與一些初秋的活動。

So we'll be visible and accessible at some point as we get closer to the end of the fourth quarter. I think we will probably have to shut down some of our public-facing engagement in anticipation results. But the timing and specific dates for that are can't comment on.

因此，隨著我們接近第四季末，我們在某些時間點仍會保持可見度並可被接觸。我認為在結果公布前的準備期，我們可能必須暫停部分對外公開的互動。但關於其時間點與具體日期，我無法評論。

Geoff Meacham, Citi.

Geoff Meacham，花旗。

I had two quick ones. The first, I know the focus on oligomers obviously differentiates you from Kisunla and McKenzie. But how would you set expectations on safety and tolerability and the differences there? I guess particularly as we get more real-world experience with these two agents, in the commercially.

我有兩個簡短的問題。第一個，我知道你們對寡聚體的聚焦顯然讓你們與 Kisunla 和 McKenzie 有所區隔。但你會如何設定大家對安全性與耐受性，以及兩者差異的預期？我想特別是隨著我們在商業化環境中，對這兩種藥物累積更多真實世界的使用經驗。

Second question, I want to get your view of the recent competitor tau data. When you think about the post-altitude data, is there a way to fast track perhaps a combo, proof of concept if you think that's a viable strategy? Thank you.

第二個問題，我想聽聽你對近期競品 tau 數據的看法。當你思考 ALTITUDE 之後的數據時，是否有方法可以加速推進、也許做一個聯合用藥的概念驗證（proof of concept），如果你認為那是可行的策略？謝謝。

Thanks, Jeff. Good questions. I think in terms of safety tolerability in sabirnetug, as we described, ALTITUDE with two active doses is intended to demonstrate a clinical efficacy signal and a risk-benefit profile, both inclusive of the clinical efficacy relative to safety that is differentiated from existing treatments. So we're hopeful and enthusiastic about that possibility.

謝謝，Jeff。好問題。我認為就 sabirnetug 的安全性與耐受性而言，如我們所描述的，ALTITUDE 以兩個有效劑量設計，目的是展示臨床療效訊號與風險—效益概況，其中也包含相對於安全性的臨床療效，並且要與現有治療有所區隔。因此我們對這個可能性抱持希望並感到振奮。

And really, just the magnitude of the study, the duration of exposure, we think it's a well-designed study to underpin and validate the oligomer hypothesis as we've positioned it. So that's our expectations for sabirnetug and ALTITUDE.

而且就研究規模與暴露期間的長度而言，我們認為這是一項設計良好的研究，可用來支撐並驗證我們所提出的寡聚體假說。所以這就是我們對 sabirnetug 與 ALTITUDE 的預期。

I think that you mentioned the, I think that you're referring to the Biogen BIIB080 program that was reported at AIC in July, and I think those are interesting data. It looks as though they'll move into a Phase 3 study for that molecule. And I think it's served as, depending on how you view it, the first clinical validation of a tau-directed approach.

我想你提到的應該是指 Biogen 的 BIIB080 計畫，該計畫在 7 月的 AIC 上有報告，我認為那些數據很有意思。看起來他們將把該分子推進到第三期研究。而且我認為，視你如何看待，它可被視為 tau 導向策略的首次臨床驗證。

Ultimately, I think we take the view that Alzheimer's is a disease that will be more adequately addressed with combination strategies. So we'll continue to evaluate ways to leverage not only our portfolio of A-beta-oligomer-directed approaches or treatments with other potentially synergistic combinations, whether it be tau or anti-inflammatory approaches.

最終，我們的觀點是，阿茲海默症將更可能透過聯合策略得到更充分的處理。因此我們會持續評估各種方式，不僅運用我們以 Aβ 寡聚體為導向的方法或治療，也會與其他可能具協同效應的組合搭配，不論是 tau 或抗發炎途徑。

But it just underpins the stage we're at in terms of establishing better treatment options for patients. And we think the future is quite bright for safer, more efficacious and more robust treatment for the early stages of the disease. And as I'm sure folks on the call are aware, the move into the preclinical population, which would be a way to avert or otherwise delay the onset of symptoms.

但這也凸顯了我們目前所處的階段：正在為病患建立更好的治療選項。我們認為未來相當光明，能在疾病早期提供更安全、更有效、且更具穩健性的治療。而且如同我相信與會者都知道的，領域也正朝向前臨床族群推進，這將是一種避免或延後症狀出現的方法。

So it's a really robust innovation ecosystem right now in the space, and we think that will continue to accelerate both commercially, with products being adopted and grown in the marketplace, and then with further research innovations that will continue to build on better options for patients.

所以目前在這個領域有非常強健的創新生態系，我們認為這將持續加速：一方面在商業面，產品會在市場上被採用並成長；另一方面也會有進一步的研究創新，持續為病患建立更好的選項。

Yeah, and then Gerrick, if I could just expand on that a little bit. In terms of safety and tolerability, there's two aspects of that that are differentiated with sabirnetug. So first of all, it's the target. It's ery selective for oligomers rather than plaque, and we think that has some potential benefits in terms of safety. And the other thing that is important to keep in mind, I think, is that this is what's called an IgG2 antibody rather than an IgG1 antibody.

是的，另外 Gerrick，如果我可以再補充一點。就安全性與耐受性而言，sabirnetug 有兩個差異化面向。首先是標的。它對寡聚體具有高度選擇性，而不是對斑塊，我們認為這在安全性方面可能帶來一些好處。另外一點我認為也很重要的是，這是一種所謂的 IgG2 抗體，而不是 IgG1 抗體。

So without going into too many details, the IgG, all the other monoclonal antibodies are IgG1s, and they have more what's called effector function. In other words, they call in your immune system to get rid of things that you don't want there. In the case of these monoclonals, it's typically plaque. And that can lead to problems like ARIA. But for an IgG2, there's less of this effector function, so it's less effect on calling in immune cells.

不深入太多細節，IgG——其他所有單株抗體都是 IgG1，它們具有較多所謂的效應功能（effector function）。換句話說，它們會召集你的免疫系統去清除你不希望存在的東西。在這些單株抗體的情境中，通常是斑塊。而這可能導致像 ARIA 之類的問題。但對 IgG2 而言，這種效應功能較少，因此在召集免疫細胞方面的作用較小。

And for our mechanism targeting oligomers, you really don't need that to happen anyway. So there's two reasons to think that our safety and tolerability could be quite good. One is that we have this differentiated target, oligomers, and the second is that we have an IgG2 antibody with less effector function and less immune system activation. So we're looking forward to seeing the data from ALTITUDE, obviously.

而以我們針對寡聚體的機制來說，其實也不需要那樣的作用發生。所以有兩個理由讓人相信我們的安全性與耐受性可能相當不錯。第一是我們有差異化的標的——寡聚體；第二是我們採用 IgG2 抗體，效應功能較少、免疫系統活化也較低。所以我們也很期待看到 ALTITUDE 的數據，這是當然的。

Dev Prasad, Lucid Capital Markets.

Dev Prasad，Lucid Capital Markets。

Just a couple of follow-up questions. First is to follow-up on the biomarker data question. Will the biomarker data will be in the top-line release, or it will follow later?

再追問兩個問題。第一個是延續生物標記數據的問題。生物標記數據會包含在主要結果（top-line）發布中，還是會在之後才公布？

And the second is, what should we expect from September 16 IRD? Will it include new EBD data or a preview of ALTITUDE analysis plan or a venue to select EBD lead candidate? Thank you.

第二個是，9 月 16 日的 IRD 我們應該期待什麼？會包含新的 EBD 數據、或是 ALTITUDE 分析計畫的預覽、或是作為選定 EBD 領先候選藥物的平台嗎？謝謝。

Thanks, Dev. So for your first question, the top-line results, as I mentioned in the prepared remarks, will include the primary outcome, the iADRS, which is a composite including both cognitive and functional measures involving the ADAS-Cog, as well as theADCS Activities of Daily Living. We'll also have the CDR Sum of Boxes, again another cognitive functional endpoint familiar to the agency and others in the field.

謝謝，Dev。針對第一個問題，如我在事先準備的發言中提到，主要結果將包含主要終點 iADRS，這是一個同時涵蓋認知與功能量測的複合指標，包含 ADAS-Cog，以及 ADCS 日常生活活動量表。我們也會提供 CDR 盒總分（Sum of Boxes），同樣是監管機構與領域內其他人士熟悉的另一個認知—功能終點。

We intentionally will include both fluid and imaging biomarkers as part of those top-line results. We really want the altitude readout to be a robust readout that really determines sabirnetug safety and clinical efficacy as part of the study design. So yes, we do anticipate having both imaging and fluid biomarkers with the top-line results late this year. (multiple speakers)

我們會刻意把體液與影像生物標記納入這些主要結果的一部分。我們非常希望 ALTITUDE 的讀出是強而有力的讀出，能在研究設計中真正判定 sabirnetug 的安全性與臨床療效。所以是的，我們預期在今年稍晚公布主要結果時，會同時提供影像與體液生物標記。（多位講者）

And then, as for IR, yeah, so I would, I mean, I would expect that to be more of a review of the investment thesis of Acumen. So whoever would like to get up to speed on sabirnetug and our EBD program prior to that Phase 2 data, that would be a good event for viewers to tune into. So yeah, please keep it on your calendar.

至於 IR，是的，我的意思是，我會預期那會更偏向回顧 Acumen 的投資論點。所以如果有人希望在第二期數據出來之前，先快速了解 sabirnetug 與我們的 EBD 計畫，那會是一個很適合收看的活動。所以，請把它記在行事曆上。

Thank you. I'm showing no further questions at this time. I'd like to turn the call back over to Alex Braun for closing remarks.

謝謝。目前顯示沒有其他問題。我想把電話會議交回給 Alex Braun 作結語。

Thanks, Michelle, and thanks to everyone for tuning in today. As always, we are at the company for follow-up questions, and I hope everyone has a wonderful day.

謝謝，Michelle，也謝謝各位今天收聽。一如往常，如有後續問題可以聯絡公司，我也祝大家有美好的一天。

Thank you for your participation. You may now disconnect.

感謝各位的參與。您現在可以斷線。