Acumen Pharmaceuticals Inc (ABOS) 2025 Q2 法說會逐字稿

Good day and welcome to the Acumen Pharmaceuticals second-quarter 2025 conference call and webcast. (Operator Instructions) As a reminder, this call may be recorded.

大家好，歡迎參加 Acumen Pharmaceuticals 2025 年第二季電話會議和網路廣播。（操作員指示）提醒一下，此通話可能會被錄音。

I would like to turn the call over to Alex Braun, Head of Investor Relations. Please go ahead.

我想將電話轉給投資者關係主管 Alex Braun。請繼續。

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, 2025.

謝謝，米歇爾。早安，歡迎參加 Acumen 電話會議，討論我們的業務更新和截至 2025 年 6 月 30 日的季度財務業績。

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

今天與我一起的有我們的首席執行官丹·奧康奈爾 (Dan O'Connell)、我們的首席開發官吉姆·多赫蒂博士 (Dr. Jim Doherty) 和我們的首席財務官兼首席商務官馬特·祖加 (Matt Zuga)。達娜（聽不清楚）準備好一些發言，然後我們將開始提問。我們的首席醫療官 Eric Siemers 博士也參加了問答環節。

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. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements.

在我們開始之前，我們鼓勵聽眾訪問 Acumen 網站的投資者部分，查看我們今天早上發布的新聞稿，我們將在今天討論該新聞稿。請注意，在今天的電話會議中，我們可能會根據聯邦證券法做出前瞻性陳述，包括有關我們的財務前景和預期業務計劃的陳述。這些聲明受風險和不確定性的影響，可能導致實際結果與前瞻性聲明中所述的結果有重大差異。

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.

請參閱我們公司介紹的第 2 張投影片、我們今天早上發布的新聞稿以及我們向美國證券交易委員會提交的最新年度和季度報告，以了解可能導致我們的實際結果與前瞻性陳述中表達或暗示的結果存在重大差異的重要風險因素。我們不承擔根據新資訊或未來結果或發展更新或修改本次電話會議或隨附簡報中提供的資訊的義務。

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

說完這些，我會把電話轉給丹。

Great. Thanks, Alex. Good morning, everyone, and thanks for joining us today. I have a few remarks to make before handing the call over to Jim to provide some details about our recently announced enhanced brain delivery or EBD program, then Matt will detail our quarterly financial results before we open the call for questions.

偉大的。謝謝，亞歷克斯。大家早安，感謝大家今天加入我們。在將電話交給 Jim 之前，我想說幾句話，讓他提供有關我們最近宣布的增強型腦輸送或 EBD 計劃的一些細節，然後 Matt 將在我們開始提問之前詳細介紹我們的季度財務業績。

The second quarter was a productive one for Acumen marked by steady operational progress and an important strategic partnership to expand our portfolio. Following the rapid completion of enrollment in our Phase 2 altitude AD study in the first quarter, we continue to make great progress with the study.

第二季度對於 Acumen 來說是富有成效的，其特點是營運穩步進展，並建立了重要的策略合作夥伴關係以擴大我們的產品組合。在第一季迅速完成第二階段高原性 AD 研究的招募工作後，我們繼續在研究上取得重大進展。

At the recent AAIC conference in Toronto, we received positive feedback from site investigators about the study design, patient retention, and our team's engagement. Based on this strong execution, we continue to expect topline results in late 2026 inclusive of the key efficacy and safety measures.

在最近於多倫多舉行的 AAIC 會議上，我們收到了現場研究人員對研究設計、患者保留率以及我們團隊參與度的正面回饋。基於這項強而有力的執行，我們繼續預期 2026 年底將出現包括關鍵功效和安全措施在內的頂線結果。

Altitude is investigating Sabirnetug, our monoclonal antibody with high selectivity for toxic Amyloid Beta oligomers. This selectivity is key to why we believe Sabirnetug could unlock potentially greater clinical efficacy and improved safety relative to antibodies targeting amyloid plaques.

Altitude 正在研究 Sabirnetug，這是我們對有毒澱粉樣蛋白 β 寡聚體具有高選擇性的單株抗體。這種選擇性是我們相信 Sabirnetug 能夠比針對澱粉樣蛋白斑塊的抗體帶來更大的臨床療效和更高的安全性的關鍵。

At AIC we also presented data showing Sabirnetug achieved the highest selectivity for Amyloid Beta over monomeric Sabirnetug when compared to [Acomanumab and Adrianumab]. The reason why this is important is that AβOs monomer levels are approximately 7,000 fold higher than the low abundance toxic ligaer levels found in the diseased Alzheimer's brain.

在 AIC 上，我們也展示了數據，顯示與單體 Sabirnetug 相比，Sabirnetug 對澱粉樣蛋白 β 的選擇性最高[阿可馬努單抗和阿德里安努單抗]。這一點很重要，因為 AβOs 單體水平比患病阿茲海默症患者大腦中發現的低豐度毒性連接蛋白水平高出約 7,000 倍。

So lower affinity for monomeric AβOs, what's demonstrates is going to increase functional selectivity because less of the antibody will be binding to monomer. I'd also like to mention that we are encouraged by the recent comments from commercial players in the space, highlighting the growth of the clinical infrastructure for diagnosing and treating people with Alzheimer's disease.

因此，對單體 AβO 的親和力較低，這表明功能選擇性會增加，因為與單體結合的抗體較少。我還想提一下，我們對該領域商業參與者最近的評論感到鼓舞，強調了診斷和治療阿茲海默症患者的臨床基礎設施的成長。

Feedback from KOLs and others in the field also have noted greater easing of clinical bottlenecks. Real-world long-term data from the currently marketed products reported at AAIC demonstrate the clinical benefit of these products growing over time, further supporting their adoption.

來自關鍵意見領袖和該領域其他人士的回饋也表明，臨床瓶頸得到了更大的緩解。AAIC 報告的當前上市產品的真實長期數據表明，這些產品的臨床益處隨著時間的推移而增長，進一步支持了它們的採用。

In addition, the first blood-based biomarker has been approved by the FDA and others are being developed. We believe blood-based biomarkers will revolutionize the field by making an accurate and potentially earlier diagnosis much more efficient. We also believe they will help expand the demand for anti amyloid treatments.

此外，首個基於血液的生物標記已獲得FDA批准，其他生物標記也正在開發中。我們相信，基於血液的生物標記將使診斷更加準確，並且可能更早，從而徹底改變該領域。我們也相信它們將有助於擴大對抗澱粉樣蛋白治療的需求。

It's terrific to see the field moving forward and the clinical infrastructure coming online as well as the increased blood-based diagnostic options for the benefit of patients and their families. This momentum we believe sets the stage for Sabirnetug and potential next-generation EBD products in the future, as there remains a very significant untreated patient population interested in receiving anti-amyloid therapy. We're excited about the potential of Sabirnetug to provide a differentiated benefit to risk treatment option for patients and the future possibility of building on that with an EBD product or products.

很高興看到該領域不斷進步，臨床基礎設施不斷上線，血液診斷選項不斷增加，為患者及其家人帶來益處。我們相信，這一勢頭為 Sabirnetug 和未來潛在的下一代 EBD 產品奠定了基礎，因為仍有大量未經治療的患者對接受抗澱粉樣蛋白治療感興趣。我們對 Sabirnetug 為患者提供差異化風險治療方案的潛力以及未來在此基礎上開發 EBD 產品的可能性感到非常興奮。

Moving to EBD in July, we announced a strategic collaboration optional license agreement with JCR Pharmaceuticals based in Japan. This collaboration is to develop an Alzheimer's disease product combining our AβO oligomer selective antibody expertise with JCR's transferrin receptor targeting blood-brain barrier penetrating technology.

7 月轉向 EBD 後，我們宣布與日本的 JCR Pharmaceuticals 達成策略合作可選許可協議。此次合作旨在將我們的 AβO 寡聚體選擇性抗體專業知識與 JCR 的轉鐵蛋白受體靶向血腦屏障穿透技術相結合，開發一種阿茲海默症產品。

We chose to partner with JCR as their established leader in the BBB space. Importantly, the partnership extends our portfolio and builds on our confidence in the potential treatment benefit of targeting toxic Aβ Oligomers

我們選擇與 JCR 合作，因為他們是 BBB 領域的領導者。重要的是，此次合作擴展了我們的產品組合，並增強了我們對針對毒性 Aβ 低聚物的潛在治療益處的信心

We've been working closely with JCR for more than a year, and I'm very excited at the potential to develop a differentiated next generation treatment option for patients and shareholders alike. We expect to make a development decision for up to two product candidates in early 2026 based on non-clinical data.

我們與 JCR 密切合作已有一年多，我對為患者和股東開發差異化的下一代治療方案的潛力感到非常興奮。我們預計在 2026 年初根據非臨床數據對最多兩種候選產品做出開發決策。

I'll now turn the call over to Jim to expand on our progress and our EBD strategy.

現在我將把電話轉給吉姆，以詳細說明我們的進展和 EBD 策略。

Thanks, Dan, and good morning everyone. Thanks for joining us today. I'd first like to build on Dan's comments about AAIC and the positive sentiment surrounding current Alzheimer's disease therapies and the potential for next generation treatments.

謝謝，丹，大家早安。感謝您今天加入我們。首先，我想基於丹對 AAIC 的評論以及對當前阿茲海默症療法和下一代療法潛力的正面情緒。

A number of KOLs have recently commented to us that if a patient is appropriate for one of the available monoclonal antibodies and makes the decision to begin treatment, compliance with the IV infusions and MR monitoring is very high.

許多關鍵意見領袖最近向我們表示，如果患者適合使用現有的單株抗體之一併決定開始治療，那麼對靜脈輸液和 MR 監測的依從性非常高。

When used in clinical practice, the safety profile of amyloid targeting antibodies appears similar to what's been reported from placebo controlled clinical trials. That said, additional improvements in the modest efficacy and reduced need for safety monitoring with the current drugs would be welcomed.

在臨床實務中使用時，針對澱粉樣蛋白的抗體的安全性與安慰劑對照臨床試驗所報告的相似。話雖如此，如果能進一步提高現有藥物的適度療效並減少安全監測的需要，我們將受到歡迎。

One of the major challenges for treating neurological disorders like Alzheimer's disease is the restriction of many therapeutic agents from entering the brain in high enough concentrations to provide therapeutic efficacy.

治療阿茲海默症等神經系統疾病的主要挑戰之一是限制許多治療藥物以足夠高的濃度進入大腦以提供治療效果。

The blood vein barrier or BBV is a system of epithelial cells that line the blood vessels in the brain that very effectively limit entry into the brain from many therapeutic agents. Selectively leveraging a process called receptor-mediated transcytosis has become an exciting technology to improve delivery of therapeutic macromolecules from the bloodstream into the brain.

血靜脈屏障或 BBV 是大腦血管內壁的上皮細胞系統，可以非常有效地限制許多治療劑進入腦部。選擇性地利用受體介導的胞吞作用已成為一種令人興奮的技術，可以改善治療性大分子從血液到大腦的傳遞。

Receptor-mediated transcytosis takes advantage of natural systems that selectively transport specific proteins into the brain, thereby delivering substantially higher amounts of enzymes or antibodies to where they need to be.

受體介導的轉胞吞作用利用自然系統選擇性地將特定蛋白質運送到大腦中，從而將大量酵素或抗體運送到需要的地方。

We have recognized for some time that this approach could benefit our program at Acumen by delivering a oligomers targeted therapeutics to the brain in a safe and effective manner. Although a number of receptors have been identified that can serve as access points for RMT technology, we have chosen the transferrin receptor as the appropriate carrier for our program based on clinical experience and the potential to mitigate the risk of ARIA associated with amyloid targeting therapeutic approaches.

我們早就認識到，這種方法可以透過以安全有效的方式向大腦提供低聚物標靶治療藥物，使 Acumen 的計畫受益。儘管已經確定了許多可作為 RMT 技術接入點的受體，但根據臨床經驗以及減輕與澱粉樣蛋白靶向治療方法相關的 ARIA 風險的潛力，我們選擇了轉鐵蛋白受體作為我們計劃的合適載體。

We conducted an extensive search and evaluation process to assess many technologies, and we're drawn to JCR because they are an established leader in the blood-brain barrier space with an approved therapy in Japan using their technology that is associated with low rates of anemia.

我們進行了廣泛的搜尋和評估過程來評估許多技術，我們之所以選擇 JCR，是因為他們是血腦屏障領域的領先者，並且在日本使用他們的技術獲得了批准，而且這種療法與低貧血率有關。

J-Brain Cargo Technology is a proprietary JCR drug delivery system that efficiently delivers drugs to target tissues, including the central nervous system through receptor mediated transatosis. It's applicable to the various modalities including antibodies, enzymes, oligonucleotides, lipid nanoparticles, gene and cell therapy, peptide and decoy receptors.

J-Brain Cargo 技術是一種專有的 JCR 藥物輸送系統，可透過受體介導的轉運有效地將藥物輸送到目標組織，包括中樞神經系統。它適用於各種方式，包括抗體、酶、寡核苷酸、脂質奈米顆粒、基因和細胞治療、勝肽和誘餌受體。

The first drug developed based on this technology is approved in Japan for the treatment of (inaudible) storage disorder exhibits an established safety profile. We have worked with JCR for more than a year on feasibility studies, and in July we announced a collaboration license and option agreement to investigate the combination of our ligament targeted antibodies with their transferrin targeted blood brain barrier technology.

基於該技術開發的第一種藥物已在日本獲得批准，用於治療（聽不清楚）儲存障礙，並表現出了既定的安全性。我們與 JCR 合作進行了一年多的可行性研究，並於 7 月宣布了一項合作許可和選擇權協議，以研究我們的韌帶靶向抗體與其轉鐵蛋白靶向血腦屏障技術的結合。

As you heard Dan discuss, we believe selectivity for synetotoxic AβO oligomers is a key opportunity for both safe and effective next generation disease modifying antibody therapy. Pairing this differentiated cargo with JCR's validated carrier technology may offer an attractive next generation product candidate for Alzheimer's patients.

正如您聽到丹所討論的，我們相信對合成毒性 AβO 寡聚體的選擇性是安全有效的下一代疾病修飾抗體療法的關鍵機會。將這種差異化的貨物與 JCR 經過驗證的載體技術相結合，可能會為阿茲海默症患者提供有吸引力的下一代產品候選。

We're investigating both Sabirnetug and other oligomer selective antibodies from our library and exploring both single chain and variable heavy domain antibody constructs with JCR, which we consider cutting edge approaches in the blood brain barrier space.

我們正在研究我們庫中的 Sabirnetug 和其他寡聚體選擇性抗體，並使用 JCR 探索單鍊和可變重域抗體構建體，我們認為這是血腦屏障領域的前沿方法。

A non-clinical candidate data package inclusive of a non-human primate study is expected in early 2026, at which point Acumen has an exclusive right to exercise our options to deliver up to two development candidates.

預計在 2026 年初將推出包含非人靈長類動物研究的非臨床候選資料包，屆時 Acumen 將擁有獨家權利行使我們的選擇權，提供最多兩種開發候選藥物。

And now I'll hand the call over to Matt.

現在我將把電話交給馬特。

Thank you, Jim. As a reminder, our second quarter of 2025 financial results are available in the press release we issued this morning and in our 10-Q, we will file later today. As of June 30, we had $166.2 million in cash and marketable securities on our balance sheet, which is expected to support our current clinical and operational activities in the early 2027. R&D expenses were $37.1 million in the first quarter, apologies in the second quarter.

謝謝你，吉姆。提醒一下，我們 2025 年第二季的財務業績可在我們今天上午發布的新聞稿和我們將在今天晚些時候提交的 10-Q 中查看。截至 6 月 30 日，我們的資產負債表上有 1.662 億美元的現金和有價證券，預計將在 2027 年初支持我們目前的臨床和營運活動。第一季研發費用為 3,710 萬美元，第二季則為 3,710 萬美元。

The increase over the prior year was primarily due to an increase for manufacturing of materials for the ALTITUDE AD clinical trial, as well as an increase in clinical expenses now that we are fully enrolled. G&A expenses were $4.6 million in the quarter, roughly flat to the same period in the prior year. This led to a loss from operations of $41.7 million and a net loss of $41 million in the quarter.

與前一年相比有所增加，主要是因為 ALTITUDE AD 臨床試驗的材料製造費用增加，以及現在我們已完全入組，臨床費用也增加了。本季的一般及行政費用為 460 萬美元，與去年同期基本持平。這導致本季營業虧損 4,170 萬美元，淨虧損 4,100 萬美元。

Finally, I would like to note that our collaboration with JCR Pharmaceuticals is a highly capital efficient way to expand our portfolio of ligamer targeted candidates. Under the terms of the agreement we announced in July, in addition to an upfront payment that JCR received, if Acumen exercises our exclusive option to develop up to two development candidates, JCR will receive an additional option payment of $9.25 million.

最後，我想指出的是，我們與 JCR Pharmaceuticals 的合作是一種高度資本有效的方式，可以擴大我們的針對連接體候選藥物組合。根據我們 7 月宣布的協議條款，除了 JCR 收到的預付款外，如果 Acumen 行使我們的獨家選擇權，開發最多兩名開發候選人，JCR 將獲得 925 萬美元的額外選擇權付款。

JCR will also be eligible to receive future milestone payments of up to $40 million related to development and up to $515 million related to sales for a total of up to $555 million, as well as single digit percentage royalties on sales of any products that emerge from the collaboration.

JCR還將有資格獲得未來與開發相關的最高 4000 萬美元里程碑付款和與銷售相關的最高 5.15 億美元里程碑付款，總計最高 5.55 億美元，以及合作中產生的任何產品銷售額的個位數百分比特許權使用費。

We are excited for the optionality and potential value this deal provides and await pre-clinical candidate data in early 2026. We are also confident in our strong execution about the (inaudible) and look forward to sharing top line results which are expected in late 2026. We remain dedicated to delivering potential next generation treatment options for the benefit of patients, caregivers, and shareholders.

我們對這筆交易提供的可選性和潛在價值感到興奮，並期待 2026 年初的臨床前候選數據。我們也對我們在（聽不清楚）方面的強大執行力充滿信心，並期待分享預計在 2026 年底實現的營收業績。我們始終致力於提供潛在的下一代治療方案，造福患者、照護者和股東。

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

這樣，我們就可以開始問答環節了。操作員？

(Operator Instructions)

（操作員指示）

Jason Zamanski, Bank of America.

賈森·扎曼斯基，美國銀行。

Morning. Thanks so much for taking our question and congrats on the progress. wanted to talk to you a little bit about AAIC. Specifically, if you look at Roche's similar sort of brain shuttling technology, the (inaudible) initial results there and how to benchmark a potential brain shuttling technology around Subernatug? And then, I guess, secondarily, given the overall plaque reduction seen in those patients, what does that mean for your epitope, given kind of the focus on the oligomers. Thanks.

早晨。非常感謝您回答我們的問題，並祝賀您的進展。想和您談談 AAIC。具體來說，如果你看一下羅氏類似的腦穿梭技術，那裡的（聽不清楚）初步結果以及如何對 Subernatug 周圍的潛在腦穿梭技術進行基準測試？其次，我想，考慮到這些患者體內斑塊總體減少的情況，考慮到對寡聚體的關注，這對您的表位意味著什麼。謝謝。

Thanks, Jason. Great question. I guess I'd like to direct that to Jim initially and Eric, you may have some comments as well.

謝謝，傑森。好問題。我想我首先想把這個問題轉給吉姆和艾瑞克，你們可能也有一些意見。

Yeah, absolutely. So yes, thanks, Jason. We've obviously been paying close attention to this entire space, including Roselli program. And I think where I'd start is where we see the opportunity for this technology is significantly enhance the ability to deliver your therapeutic target to the targeted areas in the brain.

是的，絕對是。是的，謝謝，傑森。我們顯然一直密切關注整個領域，包括羅塞利計劃。我認為我要說的是，我們看到了這項技術的機會，它顯著增強了將治療目標傳遞到大腦目標區域的能力。

And you see that certainly with the trentinimab, they see a significant change in the overall profile of the molecule from the days of delivering it directly at gantenerumab to what they're seeing now when combined with a shuttle to allow them to increase the in concentrations.

而且你可以看到，使用 trentinimab 後，他們看到分子的整體概況發生了顯著變化，從直接透過 gantenerumab 遞送到現在與穿梭機結合後，分子的濃度有所提高。

And I think we see the same kind of opportunity with Sabirnetug where, of course, their difference is in the fundamental targeting of the molecules. So -- we believe very much that these toxic naptha -- toxic oligomers are directly toxic within the brain during the pression of Alzheimer's disease.

我認為我們在 Sabirnetug 上看到了同樣的機會，當然，它們的不同之處在於分子的根本目標。因此，我們堅信這些有毒的石腦油——有毒的低聚物在阿茲海默症發作期間會直接對大腦產生毒性。

And so being able to robustly target that, we think is a mechanism that's going to lead to improvement for patients. Of course, we also see some effect on plaques, and there's a complex biology there. The amyloid biology, although we -- we all refer to amyloid as the target, and it certainly is.

因此，我們認為，能夠強而有力地實現這一目標是一種能夠改善患者病情的機制。當然，我們也看到了對斑塊的一些影響，其中存在著複雜的生物學原理。澱粉樣蛋白生物學，雖然我們都將澱粉樣蛋白稱為目標，但事實確實如此。

Amylybiology is pretty complex. And so there are ligamers associated with plaques and that's a much longer discussion. But I think where it really lands is that we see technology as enhancing the ability of Subarnatag to really effectively access silicas and we think that, that is going to be a mechanism that will be beneficial to patients.

澱粉生物學相當複雜。因此存在與斑塊相關的連接體，這是一個更長的討論。但我認為，真正的意義在於，我們認為科技增強了 Subarnatag 真正有效地獲得二氧化矽的能力，我們認為，這將是對患者有益的機制。

Eric, I don't know if you want to add anything to that?

艾瑞克，我不知道你是否想補充一點？

Yes. The only thing I might add to that is just in terms of where we are in development, I mean, Roche has done a great job in terms of their Phase 1 study, and they're obviously starting two Phase 3 studies which will take a lot to read out.

是的。我唯一想補充的是，就我們所處的開發階段而言，羅氏在第一階段研究中做得非常出色，而且他們顯然正在啟動兩項第三階段研究，這需要花費大量時間來解讀。

On the other hand, we're really looking forward to our altitude AD study with over well with 542 patients that will read out at the end of next year. And so -- but they're doing a great job with their development plan, but it's early. They're in Phase 1 right now, and we're looking forward to the results of our Phase 2 altitude study.

另一方面，我們非常期待明年年底對 542 名患者進行的高原性 AD 研究。所以——他們的開發計劃做得很好，但還為時過早。他們現在處於第一階段，我們期待第二階段海拔研究的結果。

Got it. Thanks so much for the color.

知道了。非常感謝這個顏色。

Geoff Meacham, Citi.

花旗銀行的傑夫‧米查姆。

Hi guys, It's Ross on for Jeff. I guess I just wanted to understand a little bit more kind of what you guys are hearing about the PTL 27 testing used in the screen process. Just kind of what you're hearing or any feedback or color on that from physicians in the practicing end?

大家好，我是羅斯，代替傑夫。我想我只是想進一步了解你們聽到的有關篩選過程中使用的 PTL 27 測試的資訊。您聽到了什麼，或執業醫師對此有何回饋或看法？

Thanks, Ross. -- you want to handle that maybe mention the AIC poster and some of the traction that we were getting from how we use that assay in altitude.

謝謝，羅斯。 ——你想處理這個問題，也許可以提到 AIC 海報以及我們如何在高海拔地區使用該分析方法所獲得的一些啟發。

Yeah, sure. Thanks. A great question. I really appreciate that. We as you probably know, use that as part of the screening process in our Phase 2 altitude study, and it overkill well, I think.

是的，當然。謝謝。一個很好的問題。我真的很感激。您可能知道，我們將其用作第二階段海拔研究的篩選過程的一部分，但我認為它有些過度了。

We actually in our Phase 1 study when that wasn't available over 60% of the pet scans that we obtained as part of the screening process were negative for amyloid. But when we use the screening process, and got a T2017 level first and then allowed people to go on the pet 17% of the sands were negative.

實際上，在我們第一階段的研究中，當該技術尚未普及時，作為篩檢過程的一部分，我們獲得的 60% 以上的 PET 掃描結果都未檢測到澱粉樣蛋白。但是，當我們使用篩選流程，首先獲得 T2017 級別，然後允許人們繼續使用寵物時，17% 的沙子都是陰性的。

So we didn't really want to have 0% negative because then you were too conservative in your set point. But in the poster that we had, we actually showed that as part of the screening process that actually reduced the cost by about 40%. And I think equally important, it reduces the burden for patients and their families because -- now you have our new patients going on to unnecessary pet forms and lumber countries for spinal fluid, so it worked very, very well when we're studying.

所以我們其實並不希望出現 0% 的負值，因為這樣你的設定點就太保守了。但在我們的海報中，我們實際上表明，作為篩選過程的一部分，這實際上將成本降低了約 40%。我認為同樣重要的是，它減輕了患者及其家人的負擔，因為——現在我們的新患者要去不必要的寵物醫院和木材醫院接受脊髓液檢查，所以在我們研究時，它非常非常有效。

We're pleased with those results. But more broadly kind of in your question, we're hearing a lot of positive comments from clinicians in terms of the utility of this podcast, and there will be probably other blood tests that will become available, but this is the first one to potentially get FDA approval.

我們對這些結果感到滿意。但從更廣泛的角度來看，就您的問題而言，我們聽到了很多臨床醫生對這個播客的實用性的積極評價，並且可能會有其他血液測試可用，但這是第一個可能獲得 FDA 批准的測試。

So in the future, I think you'll see a lot of clinicians applying these blood chest business screening procedure -- and that even includes primary care physicians and we're starting to see now. So certainly, the specialists that we don't talk to KOLs, they will use this, but I believe the utility of this method will become much more broad, which will get more people into the pipeline to get to these disease-modifying therapies. I'll leave it at that.

因此，在未來，我認為你會看到很多臨床醫生應用這些血液胸腔業務篩檢程序——甚至包括初級保健醫生，我們現在開始看到。因此，當然，我們沒有與 KOL 交談過的專家會使用這種方法，但我相信這種方法的用途將變得更加廣泛，這將使更多的人有機會獲得這些改善疾病的療法。我就不多說了。

Thank you.

謝謝。

Paul Matties, Stifel.

保羅馬蒂斯 (Paul Matties)，Stifel。

This is Julian on for Paul. Thanks so much for taking our question. Yeah, just again, just thinking about comparisons of CR technology to what Roche has shown. Just curious how you think you guys could potentially be differentiated particularly even on the safety side, if you have any commentary on that?

這是朱利安 (Julian) 代替保羅 (Paul)。非常感謝您回答我們的問題。是的，再次思考 CR 技術與羅氏所展示的技術的比較。只是好奇您認為您之間可能會有何區別，特別是在安全方面，您對此有什麼評論嗎？

And then just on the same topic, just wondering what you think -- I know it's early, but what the Phase 2 development could potentially look like and then sort of separately, just a broader question. There's been a lot of attention in the investor community on the early Alzheimer's studies, presymptomatic studies being conducted by Lilly and Novo. I'm just curious what you guys think of these trials? And if you have any commentary there. I'm sorry, Lilly and Eisai is what I meant there. Thanks.

然後就同一主題，只是想知道您的想法——我知道現在還為時過早，但第二階段的發展可能會是什麼樣子，然後再單獨討論，這只是一個更廣泛的問題。投資者群體對禮來公司和諾和諾德公司進行的早期阿茲海默症研究和症狀前研究給予了極大關注。我只是好奇你們對這些試驗有何看法？如果您有任何評論的話。抱歉，我指的是 Lilly 和 Eisai。謝謝。

Thanks, Jon. Yes. So I think I'll lead out, maybe, Jim, you want to comment a little bit more on the safety differentiation. And then Eric, you can comment on what we sort of talk thinking about from a clinical development standpoint. I think as we envision the JCR collaboration, there are 2 points of differentiation.

謝謝，喬恩。是的。所以我想我會帶頭，也許，吉姆，你想對安全差異發表更多評論。然後 Eric，你可以從臨床開發的角度評論我們所談論的內容。我認為，當我們設想 JCR 合作時，有兩點差異。

It's principally both on the carrier element and the way the JCR transferrin binding carrier technology may lead to better safety relative to other transferring mediated delivery modalities that actually induce a level of anemia, so I think that's one area of interest to us to exploit and potentially validate.

這主要取決於載體元素以及 JCR 轉鐵蛋白結合載體技術相對於其他實際上會引起一定程度貧血的轉鐵介導遞送方式而言可能具有更好的安全性，因此我認為這是我們感興趣的一個領域，值得我們去探索和潛在驗證。

The other is -- and Jim mentioned this in his prior comments around the cargo. And the preference of alignum-or-directed antibodies to avert even further reduce ARIA or other safety elements. So those are kind of the two primary modes of differentiation we see based on the synergistic partnership we've established with JCR.

另一個是——吉姆在之前有關貨物的評論中提到了這一點。並且優先使用定向抗體來避免進一步降低 ARIA 或其他安全因素。因此，根據我們與 JCR 建立的協同合作關係，我們看到了兩種主要的差異化模式。

Jim, I don't know if you have more comments to make. And I think we probably should talk a little bit about reference kind of the potential future clinical design for an EVD directed product.

吉姆，我不知道您是否還有其他評論。我認為我們應該稍微討論一下針對 EVD 指導產品的潛在未來臨床設計的參考類型。

Yeah, absolutely, happy to. And I think there are a number of elements that could impact a safety profile that we think -- and it's part of the reason we're excited about this approach. And I think at a high level, we see the opportunity to really lower the delivered dose because you're going to get a higher fraction of circulating dose into the brain if the technology works as it's intended, which I think is overall a good thing.

是的，非常樂意。我認為有許多因素可能會影響我們的安全狀況——這也是我們對這種方法感到興奮的原因之一。我認為，從高層次來看，我們看到了真正降低輸送劑量的機會，因為如果技術按預期運行，你將獲得更高比例的循環劑量進入大腦，我認為這總體上是一件好事。

I think when you think about safety profiles, you can look at it from the perspective of target associated things like ARIA. So that's obviously something that's top of mind for anyone developing an amyloid-based antibody approach. We're overall pleased with the profile we see for Siburnatag when it comes to REA rates, and that comes from our Phase 1 study, which we talked about a number of times.

我認為當您考慮安全設定檔時，您可以從目標相關事物（例如 ARIA）的角度來看待它。因此，對於任何開發基於澱粉樣蛋白的抗體方法的人來說，這顯然是首要考慮的事情。就 REA 利率而言，我們對西伯利亞節的概況總體感到滿意，這來自我們第一階段的研究，我們已經多次討論過該研究。

But it is interesting when you look at the work coming from the Roche Group that in their case, their antibody, the ARIA rates are much, much lower when you convert gasierimabto (inaudible) and there's scientific hypothesis around that based on where the transferrin receptors are localized, which can change the entry points for where the antibody is getting across the blood brain barrier.

但有趣的是，當您查看羅氏集團的研究成果時，就他們的抗體而言，當您將加西利馬布（聽不清楚）轉化為加西利馬佈時，ARIA 率要低得多，並且有基於轉鐵蛋白受體定位位置的科學假設，這可以改變抗體穿過血腦屏障的入口點。

So that's an interesting hypothesis and offers the opportunity to even further enhance what we think is an already attractive profile for the potential for RA risk (inaudible) and then as Dan mentioned, there are the transferrin related risks associated with things like anemia and that's certainly an element that's been reported in the Roche program to date.

所以這是一個有趣的假設，並提供了進一步增強我們認為已經很有吸引力的 RA 風險潛在特徵的機會（聽不清楚），然後正如 Dan 提到的，轉鐵蛋白相關風險與貧血等有關，這肯定是迄今為止羅氏計劃中報告的一個因素。

It's also been seen in other programs targeting the transferrin receptor, something we've thought a lot about and obviously went into our evaluation process. And we've landed with JCR because we believe that based on their clinical evidence, they've seen very low amounts of anemia with their marketed products.

在其他針對轉鐵蛋白受體的計畫中也發現了這一點，我們對此進行了大量的思考，並且顯然將其納入了我們的評估過程。我們與 JCR 合作是因為我們相信，根據他們的臨床證據，他們所銷售的產品導致貧血的幾率非常低。

And the reasons for why that might be. I think there are a number of different things we can get into, like affinity ranges for the transferrin receptor. But I think also importantly, a number of different shuttles target the transparent receptor, but they don't all necessarily target the same epitope.

以及可能的原因。我認為我們可以研究許多不同的事情，例如轉鐵蛋白受體的親和力範圍。但我認為同樣重要的是，許多不同的穿梭機都以透明受體為目標，但它們不一定都以相同的抗原決定基為目標。

And so I think -- we're learning a lot about how this technology works, but we see opportunity here to really significantly alter and improve the safety profile that we see with Siburnatag and by the way, it's a profile we're already pretty proud of. So we think there's opportunity there.

所以我認為——我們正在學習很多關於這項技術如何運作的知識，但我們也看到了機會，可以真正顯著地改變和提高西伯利亞節的安全性，順便說一句，我們已經對這個安全性感到非常自豪。所以我們認為那裡有機會。

And I think we can talk about Phase 2 study design. It is early days, as you say. The one thing I would point out there is that Eric and the team really did a fantastic job in putting together a progressive study design for some [burnatuk]-in Phase 1.

我認為我們可以討論第二階段的研究設計。正如您所說，現在還為時過早。我想指出的一點是，埃里克和他的團隊在第一階段為一些[burnatuk]制定了漸進式研究設計，確實做得非常出色。

And I think we can benefit from the approach that we took looking at both fluid and imaging-based biomarkers in AD patients with an EBD products. So I think beyond that, we'll have to see. We've got plenty of work to do before we get to that stage, but we're very proud of the work that the team did in Phase 1, and we think that, that's -- there are some insights that came out of that design that we can apply to the next program in the chain.

我認為，我們可以從使用 EBD 產品觀察 AD 患者的液體和基於成像的生物標記的方法中受益。所以我認為除此之外我們還得拭目以待。在進入該階段之前，我們還有很多工作要做，但我們對團隊在第一階段所做的工作感到非常自豪，我們認為，從該設計中得出的一些見解可以應用到鏈中的下一個程序中。

And I'll leave Eric to address your question around what we think about the preclinical studies that are ongoing right now.

我會讓艾瑞克來回答你的問題，關於我們對目前正在進行的臨床前研究的看法。

Yeah. Thanks, Jim. I think, yeah, definitely for shuttle technology, the Phase 1 even would be in patients and take some learnings from Siburnatag. But to get to your question about the clinical studies. That's something that's under active discussion.

是的。謝謝，吉姆。我認為，是的，對於太空梭技術來說，第一階段甚至會用於患者身上，並從西伯利亞節中吸取一些經驗。但要回答你關於臨床研究的問題。這是正在積極討論的事情。

I think based on our Phase 1 data, Siburnatag would be a good candidate for a preclinical trial given it's relatively low rates in our Phase 1 study. And so we're having active discussions about how that might be done. I think you could take the approach that you could use a blood-based biomarker and that's all you would need to get into a preclinical study.

我認為，根據我們的第一階段數據，Siburnatag 將是臨床前試驗的良好候選藥物，因為它在我們的第一階段研究中的發生率相對較低。因此，我們正在積極討論如何實現這一目標。我認為您可以採用基於血液的生物標記的方法，這就是進行臨床前研究所所需的全部內容。

I'm not sure that might be just a little bit too aggressive, but sort of the things we've talked about. The other thing is rather than just going straight to a pet scan, you could do essentially what we did in the Altitude study where you use the screening test, a blood test first and then depending on the apron to either spinal fluid or a pet scan.

我不確定這是否有點太過激進，但這就是我們討論過的事情。另一件事是，您不僅可以直接進行 PET 掃描，還可以像我們在 Altitude 研究中所做的那樣，先進行篩檢測試，先進行血液測試，然後根據圍裙進行脊髓液或 PET 掃描。

The other piece to this that is really evolving nicely, I think, is using -- maybe doing sort of a Phase 2 study for preclinical patients and win at biomarkers. So you look at things like PTG17 but also GFAP and a number of other measures and before you get a very large and very long Phase 3 clinical studies, you got some good evidence that your biomarkers are going the right direction, you're having the kind of effective work in a smaller Phase 2 study. And then based on that, make a decision to be a much larger Phase 3 study, which would be a (inaudible) trial. So it's something that's under active discussion are asking right now.

我認為，另一個進展順利的部分是使用——也許針對臨床前患者進行某種 2 期研究並在生物標記方面取得勝利。因此，您要查看 PTG17 之類的指標，還要查看 GFAP 和其他一些指標，在進行非常大規模和長期的 3 期臨床研究之前，您會得到一些很好的證據表明您的生物標誌物正朝著正確的方向發展，您正在進行規模較小的 2 期研究，並取得成效。然後在此基礎上，決定進行更大規模的第三階段研究，這將是一次（聽不清楚）試驗。所以這是目前正在積極討論的問題。

Thanks, Eric. And I'll just comment, Julian, that I think the rationale for oligomer directed agent in that preclinical population is very strong given the sort of the elevated levels of ligamers that sort of present and persist in that early preclinical phase of disease progression. So we're excited about that future opportunity.

謝謝，埃里克。朱利安，我只想評論一下，我認為在臨床前人群中使用寡聚體導向藥物的理由非常充分，因為在疾病進展的早期臨床前階段，連接體水平會升高，並且會持續存在。因此，我們對未來的機會感到非常興奮。

Thanks very much for the detailed responses and congrats on the progress, guys.

非常感謝大家的詳細回复，並祝賀你們的進展。

Thank you.

謝謝。

Trung Huynh, UBS.

Trung Huynh，瑞銀。

Morning, guys. Thanks for taking the question. Just following up on the asymptomatic question. And you touched upon the blood-based markers identifying this population. Just how do you see that being integrated into trying to find patients? And then just how do you see it being covered by payers. Is this something that you'll see covered readily along with pecans? Thank you.

早安，大家。感謝您回答這個問題。只是跟進無症狀問題。您也提到了識別這一人群的血液標記。您如何看待將其融入尋找患者的過程中？那麼，您認為付款人將如何承擔這筆費用？您會看到這是與山核桃一起輕易覆蓋的東西嗎？謝謝。

Thanks, Jon. Eric, do you want to take a first cut at that.

謝謝，喬恩。艾瑞克，你想先嘗試嗎？

Sure. Yeah. So there's a lot actually baked into that question. It's a good one. When you think about payers, now you're talking first about something that's available commercially and (inaudible) pace of these things. What we're hearing anecdotally is that payers are reimbursing for this L17 blood test that on this FDA approved now.

當然。是的。所以這個問題其實包含了很多內容。這是個好主意。當您考慮付款人時，您首先談論的是商業上可用的東西以及（聽不清楚）這些東西的速度。我們聽到的傳聞是，付款人正在報銷目前已獲得 FDA 批准的 L17 血液檢測費用。

And I would expect that, that would continue to be the once you have a drug that you know has a positive clinical effect in this preclinical population. In other words, you were to delay the onset of symptoms. So it is a different study design. It's not slowing the rate of decline because these people are impaired.

我希望，一旦你研發出一種你知道對臨床前族群有正面臨床效果的藥物，這種情況就會持續下去。換句話說，你應該延遲症狀的出現。所以這是一個不同的研究設計。由於這些人身體有缺陷，衰退速度並沒有減緩。

It done start to have cots decline. But I think from a payer standpoint, and this will require some discussion, but from a payer standpoint, it's there benefit within the Medicare population, let's say, but it's the benefit to be way the onset of cognitive decline because that's where health care costs start going up. So I think there's a lot of potential for this to play out clinically. But the first step, obviously, is we've got to do the study to show you that this strategy actually works. But I think it's got a lot of potential.

它確實開始出現嬰兒床下降的情況。但我認為從付款人的角度來看，這需要一些討論，但從付款人的角度來看，這對醫療保險人群來說是有好處的，但是這種好處是可以預防認知能力下降的，因為那是醫療保健成本開始上升的地方。所以我認為這在臨床上具有很大的潛力。但顯然，第一步是我們必須進行研究，以向您證明策略確實有效。但我認為它有很大的潛力。

Great, thanks.

太好了，謝謝。

Pete Stavropoulos, Cantor Fitzgerald.

皮特·斯塔夫羅普洛斯，康托·菲茨傑拉德。

Hi Dan and team congrats on progress and thank you for taking our questions. As you were mentioning before, there was a lot of excitement around biomarkers, some of which show change in biomarkers start to appear for in advance of symptoms as well as some of the underlying pathology like various pause species out of these updates, including new biomarker data at AAIC, inform your approach and assumptions about clinical studies.

嗨，丹和團隊，祝賀你們取得的進展，感謝你們回答我們的問題。正如您之前提到的，人們對生物標記非常感興趣，其中一些表明生物標記的變化在症狀出現之前就開始出現，以及一些潛在的病理，如各種暫停物種，這些更新，包括 AAIC 的新生物標誌物數據，為您的臨床研究方法和假設提供資訊。

Are there any that stand out to you? -- as ones you may look at with samples at altitude studies that you have in disclose before or incorporated into a Phase 3 study? And also curious to know if you're seeing RU rates from the Altitude study on a blinded basis. And if so, any commentary around that?

有哪些讓您印象深刻的事？ ——例如您可能在先前披露過的或納入第三階段研究的高海拔研究中看到的樣本？並且也好奇地想知道您是否在盲法基礎上看到了 Altitude 研究中 RU 率。如果是的話，對此有何評論？

Thanks, Pete. A lot in that question. I'm going to direct it to Eric for a quick comment on biomarkers of the AIC and future development opportunities.

謝謝，皮特。這個問題有很多內容。我將請 Eric 對 AIC 的生物標記和未來的發展機會發表簡短評論。

Yeah, sure. Let me just talk about the biomarker question first. I mean, as much as we all are impressed by pTau217, there's a lot of additional work going on with additional is one of the ones that is getting a lot of attention right now. So we continue to just watch that field very, very closely. Again, the results that we've had with pTau217 were, I think, quite good.

是的，當然。我先來談談生物標誌物的問題。我的意思是，儘管 pTau217 給我們留下了深刻的印象，但還有很多額外的工作正在進行中，其中額外的工作是目前受到廣泛關注的工作之一。因此，我們將繼續密切關注該領域。再次，我認為我們使用 pTau217 所取得的結果相當不錯。

And we, as you know, in our Phase 1 study, we also looked at pTau181, we look at [GFT]. We looked at the beta 42 over 40 ratio. I retire a whole series of these biomarkers that you can look at. And one of the strengths of doing that actually is when directionally, they're all going in the direction you want them to move. I think that's good evidence that you're having the right effect on the biology of the disease.

如你所知，在我們的第一階段研究中，我們也研究了 pTau181，我們研究了[GFT]。我們查看了 42 與 40 的 beta 比率。我公佈了一系列生物標誌物，供大家參考。而這樣做的好處之一就是，當它們定向時，它們都會朝著你希望的方向移動。我認為這很好地證明了你對這種疾病的生物學產生了正確的影響。

So to get to your question about ARIA, I mean we're obviously in the midst of an ongoing blinded Phase 2 study. But what I can tell you is that we've not seen any data that are inconsistent with what we reported for our Phase 1 study. So that's what I can tell you at this point.

所以回到你關於 ARIA 的問題，我的意思是我們顯然正處於一項正在進行的盲法第 2 階段研究中。但我可以告訴你的是，我們沒有看到任何與我們第一階段研究報告不一致的數據。這就是我現在能告訴你的。

Maybe I can layer a little bit on the BioMark as Eric was saying, I think there are more and more biomarkers that are coming out. And at a fairly high level, what I see is improving resolution to be able to understand disease progression.

也許我可以像 Eric 所說的那樣對 BioMark 進行一些分層，我認為會出現越來越多的生物標記。在相當高的層面上，我看到的是解析度的提高，以便能夠了解疾病的進展。

We know that Alzheimer's disease is a progressive disorder, patients progress over time. And existing diagnostics can sort of help do that diagnosis, but it's a relatively low resolution. So as more and more markers are being studied, of course, they're all peaking at different points in the disease course. And over time, multiple groups work is going to pull together, I believe, a much more high-resolution ability to understand where a given patient is in their progression of disease.

我們知道，阿茲海默症是一種進行性疾病，患者的病情會隨著時間的推移而惡化。現有的診斷方法可以在一定程度上幫助診斷，但解析度相對較低。因此，隨著越來越多的標記物被研究，當然，它們都在疾病過程的不同階段達到高峰。我相信，隨著時間的推移，多個團隊的合作將會增強，從而能夠更準確地了解特定患者的病情進展。

And hopefully, that leads to more differentiated treatment. But I think that's the long-term opportunity that I'm seeing in the blood-based biomarkers coming along. Of course, it goes without saying you've also got the benefits of convenience and cost savings and things that go along with that. But it is that ability to sort of understand disease progression at a much higher resolution that I think ultimately is going to be the biggest impact.

希望這能帶來更差異化的治療。但我認為這是我在血液生物標記中看到的長期機會。當然，不用說，您還可以享受便利、節省成本等好處。但我認為，以更高的分辨率了解疾病進展的能力最終將產生最大的影響。

All right. Thank you for that color. Just one more question, if you don't mind, on the blood-brain barrier technology. Any commentary around optionality in terms of like the design to find an optimized candidate? Will you be grafting subunits FAB fragment onto JCR's Fc backbone -- or will the graph you grab the transferrin receptor binding domain onto your antibody. Any details would be helpful. And what were some of the nonclinical data from -- or data from the feasibility studies that you sort of found encouraging and influence the decision to enter the agreement.

好的。謝謝你的顏色。如果您不介意的話，我再問一個關於血腦障壁技術的問題。對於如何透過設計找到優化候選人，您有什麼評論嗎？您是否會將亞基 FAB 片段嫁接到 JCR 的 Fc 主鏈上 - 或者您是否會將轉鐵蛋白受體結合域抓取到您的抗體上。任何細節都會有幫助。您認為哪些非臨床數據或可行性研究數據令人鼓舞並影響了您簽署協議的決定。

Go ahead. I think that's for you, Jim.

前進。我想這就是給你的，吉姆。

Yeah. Thanks, Dan. Absolutely. Yeah, Pete, so I think the opportunity here that we see and it's why we talk about it in terms of combining the cargo from the Accumen side of things with the carrier from the JCR side of things, and JCR's technology is somewhat flexible. So it allows us to investigate coupling different carrier molecules are going to have different properties. And so we're looking at things like the overall PK profile that is generated, the rates at which the drug enters into the brain, things like that.

是的。謝謝，丹。絕對地。是的，皮特，所以我認為我們看到了這裡的機會，這就是我們談論它的原因，將 Accumen 方面的貨物與 JCR 方面的承運人結合起來，而 JCR 的技術有一定的靈活性。因此，它使我們能夠研究耦合不同的載體分子將具有不同的特性。因此，我們正在研究諸如生成的整體 PK 概況、藥物進入大腦的速率等。

And I think, obviously, you're always interested in understanding safety profile. And then on the part side of things, Sabirnetugis, of course, our flagship antibody, but we do also have other antibodies in the library that Supernus came from that all have their own properties that we've characterized over time. And so you can imagine at this stage in the collaboration, we're looking at what are the best components to put together.

我認為，顯然您總是對了解安全性感興趣。然後從部分方面來看，Sabirnetugis 當然是我們的旗艦抗體，但 Supernus 所來自的抗體庫中還有其他抗體，它們都具有我們隨著時間的推移而表徵的自身特性。因此，你可以想像，在合作的這個階段，我們正在研究將哪些組件組合在一起是最好的。

And so that -- we've talked about looking at single chain variable fragment. We've talked about looking at VHHs, -- and I think combining numerous different flavors of carriers with a couple of different possible cargoes is the exercise that we're going through. And it's a really very interesting exercise because it really offers lots of different optionality. So that will be the process we need to finish up to make some decisions about which if any molecules to take forward.

因此——我們已經討論了查看單鏈變數片段。我們已經討論過 VHH 的問題——我認為將多種不同類型的運輸工具與幾種不同的可能貨物結合起來是我們正在進行的練習。這確實是一個非常有趣的練習，因為它確實提供了許多不同的選擇。因此，我們需要完成這個過程，以決定是否要繼續前進哪些分子。

And then from a little bit of color around the types of studies, we're obviously interested in ensuring that we haven't altered the properties of the cargo by coupling to the carrier. We also want to make sure that the carrier is giving us the right targeting when it comes to PK and to brain penetration. So there are a number of studies that are ongoing in preclinical species that will include a primate study to really kind of give us the characterization of the different possible combinations to pick the best ones.

然後從研究類型的一些細節來看，我們顯然有興趣確保我們沒有透過與運載工具結合而改變貨物的屬性。我們也希望確保載體在 PK 和腦穿透方面為我們提供正確的目標。因此，目前有許多針對臨床前物種的研究正在進行中，其中包括一項靈長類動物研究，以便真正讓我們了解不同可能的組合的特徵，從而選出最佳的組合。

All right. Thank you very much for taking our questions and congrats once again.

好的。非常感謝您回答我們的問題，再次表示祝賀。

(Operator Instructions)

（操作員指示）

Tom Shrader, BTIG.

BTIG 的湯姆·施拉德 (Tom Shrader)。

Good morning. This is Jenny on for Tom. And I want to ask a couple of questions on your trial. Will there be any data on the range of MMSEs in your trial? And how often are cognition tests given? Is it every six months? Or is it more often than that. Thank you.

早安.我是珍妮，代替湯姆。我想就你的審判問幾個問題。您的試驗中是否會有關於 MMSE 範圍的數據？認知測驗多久進行一次？每六個月一次嗎？或更頻繁。謝謝。

It's Eric, do you want me to go ahead and take that. Yeah. So yes, we will have MMSE as a secondary outcome. As you may know, our primary outcome is the state called the Iris which combines a cognitive measure and a functional measure.

我是艾瑞克，你想讓我繼續拍攝嗎？是的。所以是的，我們將把 MMSE 作為次要結果。您可能知道，我們的主要成果是稱為虹膜的狀態，它結合了認知測量和功能測量。

And we'll also be looking at the CDR sum of boxes that's frequently used in trials and we have a number of other secondary outcomes that affect things like quality of life and that sort of thing. Most of the mainly cognitive assessments are done every three months in the study.

我們還將研究試驗中經常使用的 CDR 總和，並且我們還有許多其他影響生活品質等的次要結果。研究中，大部分主要的認知評估每三個月進行一次。

And then, of course, we'll also have a lot of biomarker native just to take that out too. And so we're looking forward to really looking at a package data -- the one thing I might mention in terms of our data readout at the end of next year, all the data don't become available at exactly the same time. especially some of the biomarker data, it takes a while to run those assays.

當然，我們也會有很多原生的生物標記來取出。因此，我們期待真正看到一攬子數據——就明年年底的數據讀數而言，我可能會提到的一件事是，所有數據不會同時可用。特別是一些生物標記數據，運行這些分析需要一段時間。

And so our top line results will include top line efficacy and safety but some of the other more detailed biomarker results may take a little more time to become available. So when we do have our top line results, again, we'll have top line efficacy and safety, but we'll also have some additional especially biomarker results that we'll be rolling out in the subsequent view. I hope that answers your question.

因此，我們的頂級結果將包括頂級功效和安全性，但其他一些更詳細的生物標記結果可能需要更多時間才能公佈。因此，當我們確實獲得最重要的結果時，我們將再次獲得最重要的功效和安全性，但我們還將獲得一些額外的特別是生物標記的結果，我們將在後續的視圖中推出這些結果。我希望這能回答你的問題。

That does. Thank you very much.

確實如此。非常感謝。

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

謝謝。我目前沒有其他問題。我想將電話轉回給亞歷克斯·布朗，請他做最後發言。

Thanks, Michelle, and thanks to everyone for joining us today and taking the time to listen in. If you have any further questions, we are always available at the company. So please contact us. Have a great day.

謝謝，米歇爾，也謝謝大家今天加入我們並抽出時間收聽。如果您有任何其他問題，我們隨時為您服務。因此請聯繫我們。祝你有美好的一天。

Thank you for your participation. This does conclude the program. You may now disconnect.

感謝您的參與。該計劃確實就此結束。您現在可以斷開連線。