Acumen Pharmaceuticals Inc (ABOS) 2026 Q1 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Acumen Pharma first quarter 2026 conference call and webcast. (Operator Instructions) Please be advised that today's conference is being recorded.

各位好，感謝您稍候。歡迎參加 Acumen Pharma 2026 年第一季財報電話會議與網路直播。（接線員指示）請注意，今日會議將被錄音。

I would now like to hand the conference over to your first speaker today, Alex Braun, Head of Investor Relations. Please go ahead.

現在我想把會議交給今天的第一位講者，投資人關係主管 Alex Braun。請開始。

Thanks, Didi. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended March 31, 2026. With me today are Dan O'Connell, our Chief Executive Officer; and Matt Zuga, our CFO and Chief Business Officer.

謝謝你，Didi。各位早安，歡迎參加 Acumen 電話會議，討論截至 2026 年 3 月 31 日止季度的業務更新與財務結果。今天與我一同出席的有執行長 Dan O'Connell，以及財務長兼首席商務長 Matt Zuga。

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. 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.

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 醫師加入。在開始之前，我們鼓勵聽眾前往 Acumen 官網的投資人專區，查閱我們今早發布、並將於今日討論的新聞稿。

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.

請注意，在今日電話會議中，我們可能會在聯邦證券法的意義下作出前瞻性陳述，包括關於我們的財務展望與預期的業務計畫之陳述。請參閱公司簡報第 2 頁、我們今早發布的新聞稿，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。

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.

其中載有重要風險因素，可能導致我們的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所致，我們不承擔更新或修訂本次電話會議或隨附簡報中所提供資訊的任何義務。

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

接下來，我把電話交給 Dan。

Great. Thanks, Alex. Good morning, everyone, and thanks for joining us today. I ended last quarter's call by emphasizing the progress we've achieved with sabirnetug and our next-generation blood-brain barrier EBD candidates and highlighted the important work and upcoming milestones that lay ahead. That message has not changed.

很好。謝謝你，Alex。各位早安，感謝今天加入我們。我在上一季電話會議結尾時強調了我們在 sabirnetug 以及下一代血腦屏障 EBD 候選項目上所取得的進展，並指出前方重要工作與即將到來的里程碑。這個訊息沒有改變。

In the first quarter, we continued to advance sabirnetug through our Phase 2 ALTITUDE-ad trial, building on the clinical momentum established over the past year. The study remains a critical proving ground for our central scientific thesis that selectively targeting synaptotoxic Abeta oligomers rather than amyloid plaques may constitute a more effective and/or safer path forward in Alzheimer's. Execution has stayed on track. Participants have been transitioning smoothly into the 12-month open label extension study, and the conversion rate remains high.

在第一季，我們持續推進 sabirnetug 的第 2 期 ALTITUDE-ad 試驗，並延續過去一年建立的臨床動能。該研究仍是驗證我們核心科學論點的關鍵試煉場：相較於鎖定類澱粉斑塊，選擇性鎖定具突觸毒性的 Aβ 寡聚體，可能是治療阿茲海默症更有效且／或更安全的前進路徑。執行進度維持在軌道上。受試者正順利轉入為期 12 個月的開放標籤延伸研究，且轉入比例仍維持在高水準。

We see this disciplined progress as bringing us closer to a potentially differentiated treatment option for people living with Alzheimer's. We expect our top-line results for ALTITUDE-ad late this year. As we've described, ALTITUDE is designed as a low-powered study to detect statistically significant difference after 18 months on our primary clinical efficacy endpoint, the amount of slowing as measured by the iADRS.

我們認為這種有紀律的進展，正使我們更接近為阿茲海默症患者提供一個可能具差異化的治療選項。我們預期將於今年稍晚公布 ALTITUDE-ad 的主要（top-line）結果。如我們先前所述，ALTITUDE 的設計為低統計力研究，目標是在 18 個月後於主要臨床療效終點（以 iADRS 衡量的減緩幅度）上偵測統計上顯著差異。

We expect to also report on key secondary endpoints in the top-line results, such as the Clinical Dementia Rating score, Sum of Boxes, certain safety measures such as adverse event rates, including ARIA rates, and key fluid and imaging biomarkers. The study is designed to evaluate safety and efficacy of two dose levels, 35 mg/kg and 50 mg/kg compared to placebo.

我們也預期在主要結果中報告關鍵次要終點，例如臨床失智評分（Clinical Dementia Rating）之盒總分（Sum of Boxes）、某些安全性指標（如不良事件發生率，包括 ARIA 發生率），以及關鍵體液與影像生物標記。該研究旨在評估兩個劑量水準（35 mg/kg 與 50 mg/kg）相較於安慰劑的安全性與療效。

Both of the active doses are within the range of exposures shown to have exhibited pharmacodynamic target engagement in our INTERCEPT-AD Phase 1 trial. Our enhanced brain delivery, EBD program is also advancing nicely. We are conducting additional preclinical work to fully establish candidate profiles and are very pleased with the output. We intend to submit a notice to exercise our option to license two compounds developed as part of our collaboration with JCR Pharma in the second quarter of 2026. This development is imminent.

兩個有效劑量皆落在我們於 INTERCEPT-AD 第 1 期試驗中顯示具有藥效學標的結合（target engagement）的暴露範圍內。我們的增強腦部遞送（EBD）計畫也進展順利。我們正在進行額外的臨床前工作，以完整建立候選項目的特徵輪廓，且對產出結果非常滿意。我們計畫於 2026 年第二季提交通知，行使我們的選擇權，以授權取得與 JCR Pharma 合作開發的兩項化合物。此項進展已迫在眉睫。

We expect to discuss those candidate profiles in greater detail at a future medical meeting and continue to anticipate an IND filing in mid 2027. We view EBD as a way to enhance our antibodies, enabling the potential to develop treatments with increased penetration and distribution in the brain while maintaining a favorable safety profile and allowing for patient-friendly subcutaneous dosing.

我們預期在未來的醫學會議上更詳細地討論這些候選項目的特徵輪廓，並仍預計於 2027 年年中提交 IND。我們將 EBD 視為強化抗體的一種方式，使其在維持良好安全性特徵的同時，可能提升在腦內的穿透與分布，並可採用對病患更友善的皮下注射給藥。

We recognize there is competition in this space. None with an Abeta oligomer-targeted therapeutic cargo. This is where we see the potential to push the therapeutic index even further, attaining efficacy by engaging the soluble toxic species of Abeta throughout the brain. JCR, our collaborator on our EBD program, has clinically validated transferrin targeting blood-brain barrier receptor-mediated transcytosis technology. JCR has an approved therapy in Japan which incorporates their technology and has exhibited little to no anemia. This anemia safety profile offers us further potential for differentiation with our carrier plus cargo EBD product strategy.

我們了解此領域存在競爭，但目前尚無以 Aβ 寡聚體為標的、並搭載治療性載荷（therapeutic cargo）的方案。這正是我們認為可進一步提升治療指數（therapeutic index）的潛力所在：透過在整個大腦中作用於可溶性的毒性 Aβ 物種以達成療效。我們在 EBD 計畫上的合作夥伴 JCR，已在臨床上驗證其以轉鐵蛋白（transferrin）為標的的血腦屏障受體介導跨胞運輸（receptor-mediated transcytosis）技術。JCR 在日本已有一項採用其技術的核准療法，且幾乎未出現貧血或未見貧血。此貧血安全性特徵，為我們以「載體加載荷」的 EBD 產品策略提供了進一步差異化的可能性。

Taken altogether, our EBD program adds optionality to our pipeline as an additional oligomer-targeted therapeutic strategy. While not currently contemplated in our immediate clinical development plans, an anti-Abeta oligomer EBD therapeutic could also potentially be studied in preclinical Alzheimer's, a population earlier in disease course that could benefit greatly from a next-generation oligomer-directed approach.

綜合而言，我們的 EBD 計畫為產品線增添了選擇性，作為另一種以寡聚體為標的的治療策略。雖然目前未納入我們近期的臨床開發計畫，但一項抗 Aβ 寡聚體的 EBD 治療也可能在臨床前阿茲海默症族群中進行研究；該族群處於疾病進程更早期，可能會從下一代、以寡聚體為導向的方法中獲得重大受益。

The progress we've made with sabirnetug and our next-generation EBD candidates reflect the strength of our science and ability to execute and sets a solid foundation for an exciting remainder of the year. I look forward to updating you on the imminent candidate selections in our EBD program and on our ALTITUDE-ad Phase 2 results in late 2026.

我們在 sabirnetug 與下一代 EBD 候選項目上取得的進展，反映了我們科學實力與執行能力，也為今年接下來令人振奮的進程奠定了穩固基礎。我期待向各位更新 EBD 計畫中即將完成的候選項目選定，以及 2026 年稍晚 ALTITUDE-ad 第 2 期結果。

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 first 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 2025 with, excuse me. We ended March 31st with $128.4 million in cash and marketable securities on the balance sheet, which is expected to support our current clinical and operational activities into early 2027. This increase over the prior quarter is due to the private placement we completed in support of our EBD program that grossed $35.75 million, and which we announced in March of this year.

謝謝你，Dan。提醒各位，我們 2026 年第一季財務結果已載於今早發布的新聞稿，以及我們將於今日稍晚提交的 10-Q。我們在 2025 年底，抱歉更正，我們在 3 月 31 日結束時，資產負債表上的現金與有價證券為 1.284 億美元，預期可支持我們目前的臨床與營運活動至 2027 年初。相較前一季的增加，主要來自我們為支持 EBD 計畫而完成的私募增資，募集總額 3,575 萬美元，並已於今年 3 月公告。

R&D expenses were $16.5 million in the first quarter. The decrease over the prior year was primarily due to a reduction in manufacturing and material costs, as well as a reduction in CRO costs associated with our ALTITUDE-ad clinical trial, which completed enrollment in March 2025.

第一季研發費用為 1,650 萬美元。相較去年同期的下降，主要由於製造與材料成本降低，以及與 ALTITUDE-ad 臨床試驗相關的 CRO 成本下降；該試驗已於 2025 年 3 月完成收案。

G&A expenses were $4.7 million in the first quarter. The decrease primarily due to reductions in legal fees, as well as reductions in accounting, consulting, and insurance expenses. This led to a loss from operations of $21.1 million and a net loss of $20.7 million in the first quarter.

第一季一般及行政（G&A）費用為 470 萬美元。下降主要由於法律費用降低，以及會計、顧問與保險費用減少。因此，第一季營運損失為 2,110 萬美元，淨損失為 2,070 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 Abeta oligomer-targeted antibodies for Alzheimer's patients, caregivers, and stakeholders.

在我們朝今年稍晚 ALTITUDE-ad 第 2 期讀出（readout）邁進並推進 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。我們仍致力於透過以 Aβ 寡聚體為標的的抗體產品組合，為阿茲海默症患者、照護者與利害關係人創造價值。

With that, we can open the call for Q&A. Operator?

接下來，我們可以開放問答。接線員？

(Operator Instructions) Pete Stavropoulos, Cantor Fitzgerald.

（接線員指示）Cantor Fitzgerald 的 Pete Stavropoulos。

Congratulations on the continued execution of altitude. A question sort of about altitude is looking at Alzheimer's disease, similar to the approved amyloid beta antibodies. However, there are ongoing studies for preclinical Alzheimer's with a Phase 3 readout starting in 2027, assuming that altitude is positive and you move forward with sabirnetug. Could you just give us your current thoughts on which populations or patient types you would target in Phase 3 studies, what would trigger you to expand the preclinical Alzheimer's?

恭喜 ALTITUDE 持續順利執行。我有一個關於 ALTITUDE 的問題：在阿茲海默症領域，ALTITUDE 類似於已獲核准的類澱粉 β 抗體。不過，目前也有針對臨床前阿茲海默症的研究正在進行，且第 3 期讀出將自 2027 年開始。假設 ALTITUDE 結果為正、且你們推進 sabirnetug，可否談談你們目前對於第 3 期研究將鎖定哪些族群或病患類型的想法？以及什麼因素會促使你們擴展到臨床前阿茲海默症？

I can address that real quickly. In terms of our focus, we remain focused on the early AD population such as we've enrolled in altitude AD see that as the path forward for sabirnetug in a future registration study. I think our interest in the preclinical population remains quite high. And as I mentioned, potentially part of the future opportunities ahead for -- principally for a EBD candidate.

我可以很快回應。就我們的重點而言，我們仍聚焦於早期 AD 族群，也就是我們在 ALTITUDE AD 中所收納的族群；我們認為這是 sabirnetug 未來註冊性研究的前進路徑。我認為我們對臨床前族群的興趣仍然相當高。正如我提到的，這可能是未來機會的一部分——主要是針對 EBD 候選項目。

So that's not an immediate part of our plans. But certainly, I think the science and mechanism neutralizing toxic oligomers in the early course of the pathogenesis of disease is something that is promising on the horizon.

因此，這不是我們近期計畫中的立即項目。但我認為，就科學與機制而言，在疾病致病過程早期中和毒性寡聚體，是一個在地平線上相當有前景的方向。

And another question, please, on the EBD program. You do have different versions of 193 and 234. They have different PK profiles at least which we've shown to date. What are sort of the key properties and preclinical data that will drive you or drive the decision on candidate selection. And with an IND targeted, I believe, mid-2027, could you just walk us through how you're thinking about development plans and trial designs?

另外一個問題，關於 EBD 計畫。你們有不同版本的 193 與 234。至少就目前展示的資料來看，它們具有不同的藥物動力學（PK）特徵。哪些關鍵性質與臨床前數據將驅動、或說決定候選項目的選擇？另外，若 IND 目標是在 2027 年年中，可否帶我們了解你們如何思考開發計畫與試驗設計？

Sure. That's a lot, Pete. So I think, as you know, we've explored a lot of diversity in the EBD program, both from a carrier and cargo perspective, and we like sort of the -- having the ability to evaluate a series of candidates. We are down to the short list. And as I mentioned, we anticipate exercising our option for two candidates in the second quarter and remain confident that we will be filing an IND mid-2027.

當然。Pete，這內容很多。所以我想，如你所知，我們在 EBD 計畫中已經探索了相當多的多樣性，無論是從載體（carrier）或貨物（cargo）的角度來看，而我們也喜歡能夠評估一系列候選項目的能力。我們目前已縮小到短名單。如我先前提到的，我們預期在第二季對其中兩個候選項目行使我們的選擇權，並且仍有信心在 2027 年年中提交 IND。

I don't know that we can go into the details of specific PK properties. But as we have characterized, I mean, the advantages of EBD you really have to do with broad brain distribution, potentially a wider safety margin and the subcutaneous dosing convenience. So those are elements of what we are using as part of the filter for prioritizing candidates in that program.

我不確定我們是否能深入談到特定的 PK 特性細節。但如我們所描述的，EBD 的優勢主要在於更廣泛的腦部分布、可能更寬的安全性邊際，以及皮下給藥的便利性。因此，這些都是我們在該計畫中用來篩選並優先排序候選項目的要素之一。

Jim Doherty, who's on the call. I don't know, Jim, if you want to add some additional color to comment on Pete's question.

通話中有 Jim Doherty。我不知道，Jim，你是否想補充一些內容來回應 Pete 的問題。

Yes. No, I think that sounded great, Dan. I guess, Pete, the only other thing I would add, you asked about clinical program. I mean it's early days. So we're still thinking about what the early phase clinical program is going to look like. But I think we have a huge benefit in having conducted the INTERCEPT study with sabirnetug, it really gave us quite a lot of data, not only the the safety and tolerability and PK data you typically get in the Phase 1 study.

是的。不，我覺得你說得很好，Dan。我想，Pete，我唯一還想補充的是，你問到臨床計畫。我的意思是，現在還在很早期。所以我們仍在思考早期階段的臨床計畫會長什麼樣子。但我認為，我們有一個很大的優勢：我們已經用 sabirnetug 進行了 INTERCEPT 研究，這確實為我們提供了相當多的數據，不僅是你在第一期研究中通常會得到的安全性、耐受性與 PK 數據。

But since we were looking at Alzheimer's patients in the mad phase, we're able to collect data on PET imaging for a beta biochemical biomarkers for a number of different things. And that's really helped us with the sabirnetug program. And so we're actively discussing how to incorporate that kind of thinking into the early clinical studies for the EBD program. So more to come, but we're modeling what we've done on the sabirnetug program as a way to go forward.

但由於我們在 MAD 階段研究的是阿茲海默症患者，我們能夠收集到 PET 影像、β（類澱粉蛋白）生化生物標記，以及多項不同指標的數據。這些確實對 sabirnetug 計畫很有幫助。因此，我們正在積極討論如何把這種思路納入 EBD 計畫的早期臨床研究中。後續還會有更多更新，但我們正以 sabirnetug 計畫的做法作為推進的參考模型。

Jeff Letham, Citi.

Jeff Letham，花旗（Citi）。

This is [Mary Cities] on for Jeff. Just was wondering, could you please walk us through the early physician interest and feedback of sabirnetug, especially given the unmet need in early Alzheimer's and mechanism of the treatment. And then as a follow-up, could you just walk us through the ongoing regulatory interactions in anticipated discussions for the late-stage development of the program.

我是代 Jeff 發言的 [Mary Cities]。我想請問，能否帶我們了解一下醫師對 sabirnetug 的早期興趣與回饋，特別是在早期阿茲海默症仍有未被滿足需求，以及該治療機轉的背景下。接著作為追問，能否也帶我們了解一下目前持續進行的法規互動，以及對於該計畫後期開發所預期的討論。

Thanks, actually, Jim, why don't you take that Jim and Eric, I think on the feedback we've received, we've done a lot of work at meetings and visited with a number of KOLs and other clinicians that have provided a broad set of feedback on the sabirnetug program in particular.

謝謝。其實，Jim，不如你來回答這題；另外 Eric 也可以補充。我想就我們收到的回饋而言，我們在會議上做了很多工作，也拜訪了多位 KOL 與其他臨床醫師，針對 sabirnetug 計畫特別提供了廣泛的回饋。

Yes, happy to do that, Matt. And as Dan says, we've spoken to quite a number of KOLs about the sabirnetug program. And I think there's a lot of interest, obviously. I mean, we're testing a hypothesis that is slightly different than what's been tested so far with the approved therapeutics.

好的，Matt，我很樂意回答。正如 Dan 所說，我們已與相當多的 KOL 討論過 sabirnetug 計畫。我認為顯然有很高的興趣。我的意思是，我們正在驗證一個與目前已核准治療所測試內容略有不同的假說。

And I think we can talk about both what those therapies have been able to do in treating patients and where there's opportunity. And we do think that the sabirnetug approach offers a differentiated opportunity from what's been done to date.

我想我們可以談談這些療法在治療患者方面已能做到什麼，以及仍有哪些機會。我們確實認為，sabirnetug 的方法相較於迄今為止所做的，提供了一個具差異化的機會。

And I think that's generally understood by KOL. So I think everyone is very much looking forward to seeing the data. as we release the results for the altitude trial in late 2026. But I think at this point, there's a level of anticipation to see that potential for a differentiated response.

而我認為 KOL 普遍理解這一點。所以我想大家都非常期待看到數據，尤其是我們在 2026 年底公布 ALTITUDE 試驗結果時。但就目前而言，市場對於可能出現差異化反應仍抱持一定程度的期待。

Yes. And I might just add, we have spent a lot of time thinking about the differentiation of sabirnetug. And I think to sum it -- well, obviously, we don't have the data right now. We're in a [blinded] trial. But when we get the data one of the things that we'll look at, number one, would be efficacy because, again, we target all of themes, which is different than the two approved drugs.

是的。我也想補充，我們花了很多時間思考 sabirnetug 的差異化。我想總結一下——當然，我們現在還沒有數據，因為我們正在進行一項 [盲態] 試驗。但當我們拿到數據時，我們會看的第一件事是療效，因為我們的標的涵蓋所有的（相關）主題，這與兩個已核准藥物不同。

And then the second thing is we'll look to see if we can differentiate on safety because our antibody is an IgG2, the two approved antibodies or IgG1s, IgG1s have more effector function the potential for more ARIA. And so we're going to look at the safety data very carefully when those become available.

第二件事是，我們會看是否能在安全性上做出差異化，因為我們的抗體是 IgG2，而兩個已核准的抗體是 IgG1。IgG1 具有較多的效應功能（effector function），因此可能有較高的 ARIA 風險。所以當這些數據可得時，我們會非常仔細地檢視安全性數據。

Yes. And other question Yes, go ahead.

是的。還有另一個問題——是的，請繼續。

Yes. And to your question around regulatory interactions, the altitude study, of course, is running in multiple countries across multiple jurisdictions. So we're obviously speaking to regulatory agencies in the US and Canada and in Europe as part of all that.

是的。關於你問到的法規互動，ALTITUDE 研究當然是在多個國家、跨多個法域進行。因此，我們顯然也在與美國、加拿大以及歐洲的監管機構溝通，作為整體工作的一部分。

And then thinking strategically about the program or, of course, engaging with regulators about the overall progress of both of our programs, both the sabirnetug program as well as our EBD programs. And so that's that's something we'll continue to do. Obviously, it's quite important to stay in contact and to keep them apprised of progress. And so that's just the fundamental thing that we're always doing.

此外，從計畫的策略角度來看，我們也會就兩個計畫的整體進展與監管單位互動，包括 sabirnetug 計畫以及我們的 EBD 計畫。因此這是我們會持續進行的事情。顯然，保持聯繫並讓他們掌握進度非常重要，所以這就是我們一直在做的基本工作。

Paul Matteis, Stifel.

Paul Matteis，Stifel。

This is [Leon] for Paul. I wanted to say congrats on the quarter and just two quick questions for Les. As it relates to the upcoming Phase 2 readout, what do you think would be a clear win that would prove out sabirnetug to be a unique alternative to denimumab and lecanemab. And do you see kind of different scenarios at the different doses?

我是代 Paul 發言的 [Leon]。先恭喜本季表現，然後有兩個簡短問題想請教 Les。關於即將到來的第二期讀出（readout），你認為什麼樣的結果會是明確的勝利，能證明 sabirnetug 是 denimumab 與 lecanemab 之外一個獨特的替代選項？另外，你是否看到在不同劑量下可能出現不同情境？

And then as a follow-up to that, assuming success in Phase 2, would you be able to incorporate a subcutaneous arm in a Phase 3 program? And maybe any color on the subcutaneous timelines would be helpful, too.

接著追問，假設第二期成功，在第三期計畫中是否能納入皮下給藥組別？另外，如果能提供一些皮下給藥時程的資訊也會很有幫助。

Thanks, Emily. So I think in terms of a clear win in altitude AD would be an efficacy signal, at least a 30% of flow, which is sort of the maximum or the upper end of the bond, I think, for the current approved agents. So we are hopeful and anticipating that by targeting toxic species in a direct to fashion a selected fashion that it will unlock greater efficacy the safety profile,

謝謝你，Emily。我想就 ALTITUDE-AD 的明確勝利而言，會是看到療效訊號，至少達到 30% 的減緩（slowing），這大概是目前已核准藥物的上限或區間上緣。我們希望並預期，透過以更直接、且更選擇性的方式鎖定毒性物種，能解鎖更高的療效與安全性特徵。

I think there's now a real world evidence to sort of suggest what the overall rates of ARIA. And of course, those rates of area differ by genotype. And so those are some of the other elements of what we'll be looking to establish in terms of ARIA. So it's -- I think it will be the totality of the ALTITUDE-ad data and really this sort of the risk-benefit profile sabirnetug with the combination of efficacy and work safety is positioned as the primary means of differentiation relative to the current approved agents.

在安全性方面，我想現在已有真實世界證據（real-world evidence）可用來推估 ARIA 的整體發生率。而且 ARIA 的發生率當然會因基因型而異。因此，這些也是我們在 ARIA 方面要建立與確認的要素。所以——我認為會看 ALTITUDE-AD 數據的整體表現，並且就 sabirnetug 的風險效益（risk-benefit）輪廓來看，結合療效與安全性，將是相對於目前已核准藥物的主要差異化定位。

And in terms of subcu, I think we've previously guided that we will be looking at the Phase 2 data, particularly in respect of the two active doses that are being investigated in altitude to inform precisely where and how we would advance the ongoing work in subcu as part of the Phase 3 program.

至於皮下（subcu），我想我們先前已指引，我們會檢視第二期數據，特別是 ALTITUDE 中正在研究的兩個有效劑量，以精確地決定我們要在第三期計畫中於何處、以及如何推進皮下給藥的相關工作。

And I might add, Emily, I think you asked an interesting question as well around doses. As you know, there are two different doses included in the altitude study. And those doses were chosen to sort of bracket the range oligomer clearance as measured by our target engagement assay in Phase 1.

我也想補充，Emily，我覺得你關於劑量的問題也很有意思。如你所知，ALTITUDE 研究包含兩個不同劑量。這些劑量的選擇，是為了在第一期中以我們的標的結合（target engagement）檢測所量測到的寡聚體清除範圍做出上下界（bracket）。

So we think we've got an interesting range of doses chosen. And it will be -- I'll be very curious to see how that impacts the results both from a point of view of efficacy and safety, as Dan said. And so that's an interesting feature of the attitude study is that we've got both of those doses to investigate.

所以我們認為選了一個很有意思的劑量範圍。我會非常好奇這會如何影響結果，無論是從療效或安全性的角度，正如 Dan 所說。因此，ALTITUDE 研究的一個有趣特點，就是我們同時有這兩個劑量可供評估。

Yes. And just one other point about the ARIA. I think one of the concepts that's across the field now that's being better appreciated is that it's really symptomatic ARIA that you're really concerned about. And even if the symptomatic ARIA it's serious adverse events that you really worry about. So those are nearly as common, but obviously, they have a bigger impact. And so -- that's one of the things that will be benchmarking pretty carefully when we do get our data.

是的。再補充一點關於 ARIA。我想目前整個領域有一個概念正被更好地理解：真正令人擔心的是有症狀的 ARIA。甚至在有症狀的 ARIA 中，你真正擔心的是嚴重不良事件（serious adverse events）。這些並不那麼常見，但顯然影響更大。因此——當我們拿到數據時，這會是我們非常仔細用來做標竿比較（benchmarking）的其中一項。

Jason Zemansky, Bank of America.

Jason Zemansky，美國銀行（Bank of America）。

Congrats on the great progress I wanted to ask a question maybe from a different perspective here. But over the last several weeks, we've seen both the Cochrane report questioning the value of the anti-amyloid class. And I guess, a few days ago, there was an article that detailed that use of the current commercially available anti-amyloid antibodies has been slower than expected.

恭喜取得很大的進展。我想從不同角度問一個問題。在過去幾週，我們看到 Cochrane 報告質疑抗類澱粉蛋白（anti-amyloid）這一類藥物的價值。而且我想，幾天前也有一篇文章提到，目前市面上可取得的抗類澱粉蛋白抗體，其使用速度比預期更慢。

So -- as we kind of take a step back and think about both the overall unmet need and sort of the overall sort of view of the classic itself, what do you think is necessary from altitude and a sort of Phase 3 you do to really demonstrate that there's a level of differentiation here as well as overall efficacy to the point that it sort of turns back some of the skeptism.

所以——當我們稍微退一步，思考整體未被滿足的需求，以及對於這個「經典」本身的整體觀點時，你認為從 ALTITUDE 以及你在第三期（Phase 3）會做的事情來看，究竟需要哪些要素，才能真正證明這裡存在一定程度的差異化，同時也能展現整體療效，進而在某種程度上扭轉部分的懷疑？

Jason -- so I think in terms of the top on the port, I think there's been a good bit of follow-up in terms of the methodology there. And I think there's your question about kind of the merits of the approach from a methodology standpoint, I do think that I'm familiar with the stat article as well.

Jason——我想就「top on the port」而言，我認為在方法學方面已經有相當多的後續追問。我也理解你問的是，從方法學角度來看這種做法的優點。我也確實熟悉那篇 STAT 的文章。

And I think it speaks to sort of two things, the unmet need and the demand for better options and the fact that there is -- the clinical infrastructure is now -- has been established and continues to adopt and progress the make available these first couple of agents and build out essentially the marketplace. I think what the market is looking for is a more clear value proposition in terms of the risk-benefit profile. And that's really where leading ALTITUDE-ad and validating the oligomer hypothesis.

我認為那篇文章其實談到兩件事：未被滿足的需求與對更好選項的需求，以及目前臨床基礎設施已經——已建立，並且持續採用、推進，讓前幾個藥物得以上市並逐步擴建，基本上是在打造市場。我認為市場在尋找的是在風險—效益（risk-benefit）輪廓上更清楚的價值主張。而這正是推進 ALTITUDE-ad 並驗證寡聚體（oligomer）假說的關鍵所在。

I think acumen and sabirnetug really attractive position from a timing perspective sort of reenergized the space and position next-generation treatment options. I think the field has progressed over a number of years to develop better insights into clinical trial design, which patients to treat underlying aspects of the pathophysiology of the disease. And so we view sabirnetug as sort of that next position advancing the field forward on the basis of positive data.

我認為 Acumen 與 sabirnetug 在時機點上處於非常有利、也很吸引人的位置，某種程度上重新點燃了這個領域，並把下一代治療選項擺到更前面。這個領域多年來持續進展，對臨床試驗設計、該治療哪些病人，以及疾病病理生理的底層面向，都有了更好的洞見。因此我們把 sabirnetug 視為在正向數據基礎上，推動領域向前的下一個位置。

And I might just add, I was recently at the American Academy of Neurology meeting in Chicago. And these are practicing neurologists for the most part. There was a great deal of interest and enthusiasm for information concerning the two approved drug, lecanemab and donanemab.

我再補充一下，我最近在芝加哥參加美國神經學學會（American Academy of Neurology, AAN）年會。與會者多半是臨床執業的神經科醫師。大家對兩個已核准藥物——lecanemab 與 donanemab——的相關資訊展現出高度興趣與熱情。

So even though there have been these relatively negative analysis, and again, as Dan mentioned, the comp report was pre flawed and a lot of people's opinions in terms of how they did the analysis. I think if you actually talk to neurologists, they understand that the infrastructure has been rate-limiting but that infrastructure is going to continue to improve. And so there is a lot of interest from neurologists at the AAN meeting.

所以即便有一些相對負面的分析——而且如 Dan 提到的，那份 comp 報告在很多人看來本來就有缺陷，尤其是分析方式——但我認為如果你實際去和神經科醫師交流，他們理解限制因素一直是基礎設施（infrastructure），但那個基礎設施會持續改善。因此在 AAN 年會上，神經科醫師的興趣非常高。

Tom Shrader, BTIG.

Tom Shrader，BTIG。

This is Jenny Kim on for Tom Shrader. At altitude approaches the late 2026 top line readout, could you give us some additional color on the blinded operational metrics are tracking things like protocol deviation rate site level of patterns or any shifts in enrolled patient population profile relative to your original assumptions, more broadly, what distinguishes the quality of the data set relative to prior anti-amyloid trials?

我是代替 Tom Shrader 的 Jenny Kim。隨著 ALTITUDE 逐步接近 2026 年底的主要（top-line）讀出，你們能否就盲態（blinded）的營運指標提供更多說明，例如方案偏離率（protocol deviation rate）、各試驗中心層級的模式，或是相較於你們原先假設，已入組病人族群特徵是否有任何變化？更廣泛地說，相較於先前的抗類澱粉蛋白（anti-amyloid）試驗，你們這套資料集的品質有何不同之處？

Do you want to lead out on that and Eric provide some color?

你要先帶頭回答，然後 Eric 再補充一些細節嗎？

Yes. Jenny, I'll give you a first pass and then ask Eric to weigh in. I think probably the best thing to say is that we, at this point, have been very pleased with the progress of the attitude study. Any of these studies is a 542 subject study.

好的。Jenny，我先簡單回覆，然後請 Eric 再補充。我想最好的說法是：截至目前，我們對 ALTITUDE 研究的進展非常滿意。這類研究都是 542 名受試者的研究。

There's a lot of data and a lot of information flowing in the study. but we've been relatively pleased with the conduct of the study. It's a great team that is working extremely hard across multiple geographies to deliver the data. And I think to date, we have been tracking to the assumptions that we built into our study design. So we are -- we have confidence in our study design as well. And I'll turn it over to Eric to give you any specific commentary.

研究中會有大量數據與資訊持續流入，但我們對研究的執行表現相對滿意。有一個非常優秀的團隊在多個地理區域非常努力地工作，以交付數據。而且截至目前，我們的進度與我們在研究設計中所建立的假設一致。因此我們——也對研究設計本身有信心。接下來我把時間交給 Eric，看看他是否有更具體的補充。

Yes. So thanks for the question. The study is progressing quite well. I think as you know, we completed enrollment in a very short period of time in 10 months. One of the things that we did in our study, which is being done in other studies, that is quite innovative, I think, was to use this plasma PTL 217 test as part of a screening procedure.

好的，謝謝你的問題。研究進展相當順利。如你所知，我們在很短的時間內完成入組——10 個月。研究中我們做的一件事（其他研究也在做），我認為相當創新，就是把血漿 PTL 217 檢測納入篩檢流程的一部分。

So in other words, when we did our Phase 1 study to get into the study, you had to have a positive PET scan and it turned out that about 60% of the time, the PET scans were negative. When we added this blood test, simple blood test as a screening step before you got to PET schemes, the rate of negative pet scans drop from, again, around 60% to under 20%.

換句話說，在我們第一期（Phase 1）研究中，要進入研究你必須有 PET 掃描陽性，但結果大約有 60% 的情況 PET 掃描是陰性。當我們在進行 PET 檢查之前，先加入這個血液檢測（簡單的抽血檢測）作為篩檢步驟後，PET 陰性的比例就從約 60% 降到 20% 以下。

So it made the screening process much better. We heard feedback from the sites that they really like that approach. I think that's something that could be used in clinical practice. And actually at the American Academy of Neurology meeting, there was a lot of discussion about how you would use these plasma biomarkers as part of your screening process for patients.

因此篩檢流程變得更有效率。我們也從各試驗中心收到回饋，他們非常喜歡這種做法。我認為這也可能在臨床實務中使用。事實上，在美國神經學學會年會上，也有很多討論聚焦在如何把這些血漿生物標記（plasma biomarkers）納入病人的篩檢流程。

So we were really very pleased how that worked out in our trial, and we're looking forward to seeing that utilized in clinical practice.

所以我們對它在試驗中的表現非常滿意，也期待未來能在臨床實務中被採用。

Dev Prasad, Lucid Capital Markets.

Dev Prasad，Lucid Capital Markets。

Congrats on the progress. Just following up on the previous question regarding Phase 2 doses how much separation between 35 mg and 50 mg do you expect? And what would you need to see to select a Phase 2 dose -- also on EBD program. Can you provide more detail on 14 to 40x higher brain exposure that you observed in the primates. What differentiated those exposures such as dose, road, brain, distribution, et cetera?

恭喜進展順利。延續上一題關於第二期（Phase 2）劑量的問題，你們預期 35 mg 與 50 mg 之間會有多大的差異？你們需要看到什麼，才會選定第二期劑量？另外關於 EBD 計畫：你們能否更詳細說明在靈長類中觀察到腦部暴露量（brain exposure）提高 14 到 40 倍的結果？造成這些暴露差異的因素是什麼，例如劑量、給藥途徑（route）、腦部分布（distribution）等等？

Thanks, Dev, Jim I'm going to direct put those right to you.

謝謝你，Dev。Jim，我把這些問題直接交給你回答。

Yes, Dev, so happy to take those questions. So when we think about dosing for the altitude study, first. The doses are 35 mg per kg and 50 mg per kg. And I was mentioning earlier, the doses were sort of chosen with the idea in mind that, that is what looks to be a key part of the dynamic range and exposure of Siboligmers, which, of course, is our key primary target. And I think there's the opportunity to see affects differential effects of the 2 doses in a couple of different ways. I mean we'll have to wait and see what the data actually show.

好的，Dev，很樂意回答。先談 ALTITUDE 研究的給藥。劑量是每公斤 35 mg 與每公斤 50 mg。我先前提到，選擇這些劑量的想法是：這看起來涵蓋了 Siboligmers 的動態範圍與暴露量中的關鍵區段，而這當然是我們最主要的首要標的。我認為有機會從幾個不同面向看到兩個劑量的差異效應——當然我們得等實際數據出來才知道。

But one possibility is differences in efficacy. You might expect to see dose-related differences in efficacy. Although I think part of what we're testing there is what the role of the Siboligamers is and how that's different from what you've seen to date with more plaque targeting antibodies. So in some ways, the lower dose may give more of an game specific signal, although we do expect some contribution from other species of a beta even at that dose.

其中一種可能是療效差異。你可能會預期看到與劑量相關的療效差異。不過我認為我們在測試的一部分，是 Siboligamers 的角色，以及它與迄今為止你在較偏向斑塊（plaque）靶向抗體所看到的結果有何不同。某種程度上，較低劑量可能會提供更偏向該機制的特異性訊號，儘管即使在那個劑量下，我們也預期其他 Aβ 物種仍會有一些貢獻。

And then certainly, as you go to a higher dose, you would expect some additional effects on larger species as we've seen in the INTERCEPT study in Phase 1. And I think also, 1 might expect there could be some differences in tolerability, right? I mean that would be again, consistent with the Phase 1 data. So we're very excited to see the study at the end of the year, and we'll be looking at all of these things for differential effects at multiple doses.

而當你提高到更高劑量時，你會預期對較大物種會有一些額外效應，正如我們在第一期 INTERCEPT 研究中所看到的。我也認為，人們可能會預期耐受性（tolerability）上會有一些差異，對吧？這同樣會與第一期數據一致。因此我們非常期待在今年底看到研究結果，並會在多個劑量下檢視所有這些可能的差異效應。

And then I think your other question around the EBD programs. So of course, what we're trying to achieve is both an improvement in brain penetration, but also the brain distribution of our aligner targeting antibodies by coupling with the carrier technology from JCR. And so what we've done is we've investigated multiple candidates is we've been able to vary both sides of that equation.

接著談你關於 EBD 計畫的問題。我們當然希望達成的是：不僅提升腦部穿透（brain penetration），也改善我們寡聚體靶向抗體在腦內的分布（brain distribution），方法是與 JCR 的載體（carrier）技術進行偶聯。因此我們做的是：評估多個候選分子，並能在這個等式的兩端都做變化。

So looking at the changes to the carrier choices from JCR as well as modifications on the cargo side. And really, the quick way to summarize it is what you're seeing is a range of substantial improvements in brand exposure. And that's in both rodent studies in humanized receptor. And then also in primate studies. And so we're looking at multiple brain regions and so in the primate study.

也就是同時觀察 JCR 載體選擇的變更，以及在「貨物端」（cargo side）的修飾。簡單總結，你看到的是腦部暴露量顯著改善的範圍。這些結果來自囓齒類研究（在人源化受體模型中），也來自靈長類研究。我們也在靈長類研究中觀察多個腦區。

And so we're seeing really substantial improvements and you quoted the range between five-fold and 40-fold improvements in exposure. And so we're seeing both that improved brain penetration as well as distribution. And we really think it's both properties that are part of what makes this technology so exciting for the treatment of Alzheimer's and specifically for soluble oligomer approach. So that's what I can say to date. We are keeping a close eye on which are the best candidates to give us the broadest distribution in multiple brain regions.

因此我們看到非常顯著的改善——你提到的暴露提升範圍介於 5 倍到 40 倍。我們同時看到腦部穿透提升以及分布改善。我們確實認為，這兩個特性共同構成了這項技術對阿茲海默症治療、尤其對可溶性寡聚體策略而言如此令人振奮的原因。就目前我能分享的大概是這些。我們也會密切關注哪些候選分子能在多個腦區提供最廣泛的分布。

Thank you, this concludes our question-and-answer session and also today's conference call. Thank you for participating, and you may now disconnect.

謝謝各位，問答環節以及今天的電話會議到此結束。感謝您的參與，您現在可以掛線。