Voyager Therapeutics Inc (VYGR) 2024 Q3 法說會逐字稿

Good afternoon and welcome to the Voyager Therapeutics third-quarter 2024 financial results conference call. (Operator Instructions) Please note that today's call is being recorded. A replay of today's call will be available on the Investors section of the company website approximately two hours after completion of this call.

下午好，歡迎參加 Voyager Therapeutics 2024 年第三季財務業績電話會議。（操作員指示）請注意，今天的通話正在錄音。本次電話會議結束後約兩小時，公司網站的「投資者」部分將提供今天電話會議的重播。

I would now like to turn the call over to Trista Morrison, Chief Corporate Affairs Officer at Voyager.

現在我想將電話轉給 Voyager 首席企業事務官 Trista Morrison。

Thank you, and good afternoon. We issued our third-quarter 2024 financial results press release this afternoon. The press release and 10-Q are available on our website. Joining me on today's call are Dr. Al Sandrock, our Chief Executive Officer; and Dr. Todd Carter, our Chief Scientific Officer. We will also be joined for the Q&A portion of the call by Nathan Jorgensen, our Chief Financial Officer.

謝謝，下午好。我們今天下午發布了 2024 年第三季財務業績新聞稿。新聞稿和 10-Q 可在我們的網站上查閱。參加今天電話會議的還有我們的執行長 Al Sandrock 博士；以及我們的首席科學官 Todd Carter 博士。我們的財務長 Nathan Jorgensen 也將參與本次電話會議的問答環節。

Before we get started, I would like to remind everyone that during this call, Voyager representatives may make forward-looking statements as noted in slide 2 of today's deck. These statements are based on our current expectations and beliefs. They are subject to risks and uncertainties and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings which are available on our website for additional detail.

在我們開始之前，我想提醒大家，在這次電話會議中，Voyager 代表可能會做出前瞻性陳述，如今天的簡報第 2 張投影片中所述。這些陳述是基於我們目前的期望和信念。它們受風險和不確定性的影響，我們的實際結果可能存在重大差異。我鼓勵您查閱我們網站上的美國證券交易委員會文件中討論的風險因素，以獲取更多詳細資訊。

Now I will turn the call over to Al.

現在我將電話轉給 Al。

Good afternoon, everyone, and thank you for joining us. Please turn to slide 3. At Voyager, we are leveraging the power of human genetics to discover and deliver transformative medicines that address the root cause of neurological diseases.

大家下午好，感謝大家的參與。請翻到幻燈片 3。在 Voyager，我們利用人類遺傳學的力量來發現和提供解決神經系統疾病根本原因的變革性藥物。

Our four pillars of value include first, our pipeline of four wholly owned and 14 partnered programs. During the third quarter, we completed enrollment and dosing in the single ascending dose trial of VY7523, our anti-tau antibody for Alzheimer's disease. We also recently saw encouraging third-party clinical data with another anti-tau antibody for Alzheimer's disease, which Toby will talk about shortly.

我們的四大價值支柱包括：第一，我們的四個全資項目和 14 個合作項目。在第三季度，我們完成了對阿茲海默症的抗 tau 抗體 VY7523 的單次遞增劑量試驗的招募和給藥。我們最近也看到了另一種針對阿茲海默症的抗 tau 抗體的令人鼓舞的第三方臨床數據，Toby 稍後將對此進行討論。

Our second pillar of value is our industry-leading TRACER platform for the discovery of novel AAV capsids to enable CNS gene therapy. These IV-delivered CNS targeted capsids underlie all of our wholly owned and partner gene therapy programs, and we expect IMDs for three of these programs next year.

我們的第二個價值支柱是業界領先的 TRACER 平台，用於發現新型 AAV 衣殼，實現 CNS 基因治療。這些透過靜脈注射 (IV) 遞送的中樞神經系統 (CNS) 標靶衣殼是我們所有全資和合作基因治療計畫的基礎，我們預計明年其中三個計畫將採用 IMD。

Third, we have blue-chip partnerships with some of the world's experts in neurology and gene therapy including Neurocrine, Novartis, and Alexion. We continue to progress these partnerships through the third quarter with Novartis signing on for a fifth partner -- program partnership and Neurocrine nominating a third development candidate.

第三，我們與一些世界神經病學和基因治療領域的專家建立了良好的合作關係，包括 Neurocrine、Novartis 和 Alexion。我們在第三季繼續推進這些合作，諾華簽約了第五個合作夥伴——專案合作夥伴，而 Neurocrine 提名了第三個開發候選人。

Finally, we continue to explore the potential to leverage receptors we have identified to shuttle non-viral genetic medicines into the brain. Ultimately, we aim to expand from gene therapy and antibodies into other modalities of neurogenetic medicine, broadening our impact.

最後，我們繼續探索利用已鑑定的受體將非病毒基因藥物運送到大腦的潛力。最終，我們的目標是從基因治療和抗體擴展到神經遺傳醫學的其他方式，擴大我們的影響力。

With that, I'll turn the call over to Toby to talk more about our anti-tau antibody and some of the recent third-party data in the space.

接下來，我將把電話轉給托比，進一步討論我們的抗 tau 抗體以及該領域的一些最新第三方數據。

Thanks, Al, and good afternoon. Please turn to slide 4. This slide summarizes the four wholly owned programs and 14 partner programs that Al mentioned earlier. Today, we are going to focus on our tau-targeting programs for Alzheimer's disease.

謝謝，艾爾，下午好。請翻到幻燈片 4。這張投影片總結了 Al 之前提到的四個全資項目和 14 個合作夥伴項目。今天，我們將重點介紹阿茲海默症的 tau 靶向計劃。

Turning to slide 5, the point I want to make here is that we view tau as a critically important target for the treatment of Alzheimer's disease. As you can see an image on the left of this slide, the spread of pathological tau as identified on tau PET imaging correlates closely to Alzheimer's disease progression as measured by Braak clinical pathologic staging. Additionally, exploratory clinical data from Biogen's BIIB080 tau knockdown program showed a reduction in pathological tau as well as potentially greater slowing of clinical disease progression than seen with anti-amyloid antibodies.

轉到幻燈片 5，我在這裡想要說明的一點是，我們認為 tau 是治療阿茲海默症的至關重要的目標。正如您在這張幻燈片左側看到的，tau PET 成像中發現的病理性 tau 的擴散與 Braak 臨床病理分期測量的阿茲海默症進展密切相關。此外，Biogen 的 BIIB080 tau 敲低計畫的探索性臨床數據顯示，與抗澱粉樣蛋白抗體相比，病理性 tau 減少，且臨床疾病進展可能進一步減緩。

So, in short, we think targeting tau has the potential to impact Alzheimer's disease progression and do so in a significant way. This is why Voyager is pursuing two approaches to targeting tau: our anti-tau antibody VY7523 and our tau-silencing gene therapy.

簡而言之，我們認為針對 tau 有可能對阿茲海默症的進展產生重大影響。這就是為什麼 Voyager 正在採取兩種針對 tau 的方法：我們的抗 tau 抗體 VY7523 和我們的 tau 沉默基因療法。

On slide 6, I want to highlight how the team selected our anti-tau antibody. We started with more than 700 antibodies across the mid-domain and C-terminus of tau. We first focused on antibodies targeting pathological tau. This was important with the anti-amyloid antibodies. Several that failed such as solanezumab or bapineuzumab were shown to have insufficient target engagement with aggregated forms of amyloid beta, while the approved anti-amyloid antibodies all target the aggregated species.

在第 6 張投影片上，我想重點介紹團隊如何選擇我們的抗 tau 抗體。我們從 tau 中段和 C 端的 700 多種抗體開始。我們首先關注針對病理性 tau 的抗體。這對於抗澱粉樣蛋白抗體來說很重要。一些失敗的藥物如 solanezumab 和 bapineuzumab 被證明與聚集形式的澱粉樣β蛋白的標靶作用不足，而已核准的抗澱粉樣蛋白抗體都以聚集物種為目標。

We narrowed the funnel through further in vitro and in vivo studies. We evaluated antibodies targeting various epitopes across tau including in the mid-domain and the C-terminus of tau. In a mouse seeding model of human pathological tau spread, the C-terminal-targeted antibody Ab01, the mirror inversion of VY7523 decreased the spread of injected pathological human tau by approximately 70%. Based on these data and the specificity for pathological tau, we selected VY7523 as our clinical candidate.

我們透過進一步的體外和體內研究縮小了漏斗範圍。我們評估了針對 tau 中不同抗原決定位點的抗體，包括 tau 的中間域和 C 端。在人類病理性 tau 擴散的小鼠接種模型中，C 端靶向抗體 Ab01，VY7523 的鏡像反轉使注射的病理性人類 tau 的擴散減少了約 70%。根據這些數據和對病理性 tau 的特異性，我們選擇 VY7523 作為我們的臨床候選藥物。

We also conducted a series of head-to-head studies in the same model against other antibodies. These data are summarized on slide 7.

我們也在同一模型中針對其他抗體進行了一系列頭對頭研究。這些數據已在第 7 張投影片中進行了總結。

In the first head-to-head study, we evaluated murine 7523 against murine versions of Biogen’s gosuranemab and Lilly's zagotenemab. These antibodies both targeted the N-terminus of tau and both failed their primary end points in clinical trials. Both were ineffective at reducing tau spread in the model, while our C-terminal targeted antibody again blocked tau spread. This gave us confidence that the model had negative predictive value.

在第一次頭對頭研究中，我們評估了小鼠 7523 與 Biogen 的 gosuranemab 和 Lilly 的 zagotenemab 的小鼠版本。這些抗體均以 tau 的 N 端為目標，且均在臨床試驗中未能達到其主要終點。兩者均無法減少模型中的 tau 擴散，而我們的 C 端靶向抗體再次阻斷了 tau 擴散。這使我們相信該模型具有陰性預測值。

In the second head-to-head study, we compared our C-terminal targeted antibody to UCB's bepranemab, which targets the mid-domain. In our models, both antibodies inhibited tau spread. Based on these data, we were eager to see the results from the bepranemab clinical trial, because we thought that if this antibody could impact tau in a clinical trial, then our model might also have positive predictive value.

在第二次頭對頭研究中，我們將我們的 C 端靶向抗體與 UCB 的靶向中域的 bepranemab 進行了比較。在我們的模型中，兩種抗體都抑制了 tau 擴散。基於這些數據，我們迫切希望看到 bepranemab 臨床試驗的結果，因為我們認為，如果這種抗體能夠在臨床試驗中影響 tau，那麼我們的模型也可能具有積極的預測值。

Turning to slide 8, I want to summarize the recent bepranemab data shared at the 2024 CTAD meeting. I want to start by noting that the primary endpoint CDR sum of boxes was not met in the full study population. This is important to acknowledge.

前往第 8 張投影片，我想總結一下 2024 年 CTAD 會議上分享的最新 bepranemab 數據。首先我想指出的是，整個研究族群的主要終點 CDR 框總和並未達到。承認這一點很重要。

Now, I would like to note that bepranemab inhibited the accumulation of tau in human brain by 33% to 58%. We saw this as establishing that an antibody can be used to inhibit the spread of pathological tau in the brain. This finding should not be underestimated as I think that after the failure of the N-terminal anti-tau antibodies, there was uncertainty in the industry as to whether an antibody approach could impact tau accumulation. As it turns out, it can.

現在，我想指出的是，bepranemab 抑制了人類大腦中 tau 的累積 33% 到 58%。我們認為這證實了抗體可用於抑制腦內病理性 tau 的擴散。這項發現不容小覷，因為我認為在 N 端抗 tau 抗體失敗後，業界對於抗體方法是否會影響 tau 累積存在不確定性。事實證明，是可以的。

I also want to note that bepranemab slowed cognitive decline by 21% to 25% versus placebo per ADAS-Cog 14. Additionally, in sub-group analyses, it seems that patients with the greatest reduction in tau burden had more consistent clinical benefit, although we will need to see more detailed PK/PD and PD clinical correlation analysis.

我還想指出的是，根據 ADAS-Cog 14，與安慰劑相比，bepranemab 可將認知能力下降減緩 21% 至 25%。此外，在亞組分析中，tau 負擔減少最多的患者似乎具有更一致的臨床益處，儘管我們需要看到更詳細的 PK/PD 和 PD 臨床相關性分析。

Finally, bepranemab demonstrated an acceptable safety profile with brain hemorrhagic and inflammatory changes similar to placebo. What does this mean for Voyager's VY7523? I would say that these data give us increasing confidence that antibody targeting the appropriate epitope of tau can slow the accumulation of tau in the brain of Alzheimer's patients. And that this slowing may offer a clinically significant benefit in some patients. This was a top-line data presentation, and there is certainly more work to be done here. And we look forward to seeing the additional data.

最後，bepranemab 表現出了可接受的安全性，其腦出血和發炎變化與安慰劑相似。這對 Voyager 的 VY7523 意味著什麼？我想說，這些數據讓我們越來越相信，針對 tau 適當表位的抗體可以減緩阿茲海默症患者大腦中 tau 的累積。這種減緩可能為某些患者帶來具有臨床意義的益處。這是一份頂線數據展示，這裡肯定還有更多的工作要做。我們期待看到更多數據。

Slide 9 provides an overview of our Phase 1 clinical development plan for VY7523. During the third quarter, we completed enrollment and dosing of healthy volunteers in our single ascending dose trial. We expect to report top-line safety and pharmacokinetic data in the first half of next year. We expect to initiate a multiple ascending dose trial in patients with early Alzheimer's disease next year and generate initial tau PET imaging data in the second half of 2026.

投影片 9 概述了我們針對 VY7523 的第 1 階段臨床開發計畫。在第三季度，我們在單次遞增劑量試驗中完成了健康志願者的招募和給藥。我們預計在明年上半年報告頂級安全性和藥物動力學數據。我們預計明年將對早期阿茲海默症患者啟動多次遞增劑量試驗，並在 2026 年下半年產生初始 tau PET 影像數據。

At this point, we don't see anything in the bepranemab data that would shift our thinking here. If anything, the data reaffirmed that tau PET imaging is the critical outcome we want to focus on, and we have planned a very efficient trial focused on that outcome. We found the safety profile of bepranemab encouraging and look forward to exploring the full range of dosing possibilities.

到目前為止，我們還沒有在 bepranemab 數據中看到任何可以改變我們想法的東西。無論如何，數據再次證實了 tau PET 成像是我們想要關注的關鍵結果，我們已經計劃針對該結果進行非常有效的試驗。我們發現 bepranemab 的安全性令人鼓舞，並期待探索全方位的給藥可能性。

I mentioned earlier that we are advancing two approaches to targeting tau for Alzheimer's disease. We focused a lot on the antibody approach today in light of the recent third-party data.

我之前提到過，我們正在推進兩種針對 tau 治療阿茲海默症的方法。根據最近的第三方數據，我們今天將重點放在抗體方法上。

But I will now turn the call over to Todd to touch on our other approach.

但現在我將把電話轉給托德，談談我們的另一種方法。

Thanks, Toby, please turn to slide 10. In addition to our antibody-based approach, we are also advancing the tau-silencing gene therapy program. This program deploys a tau-targeted siRNA, packaged in an IV-administered TRACER capsid. Using this approach, we have demonstrated robust productions in human tau in mRNA and protein across the brain following a IV single administration in mice that express human tau as shown on the slide.

謝謝，托比，請翻到第 10 張投影片。除了基於抗體的方法外，我們還在推進 tau 沉默基因療法計劃。該程序部署了 tau 靶向 siRNA，包裝在透過 IV 注射的 TRACER 衣殼中。利用這種方法，我們已證明，在對錶達人類 tau 的小鼠進行單次靜脈注射後，整個大腦中人類 tau 的 mRNA 和蛋白質含量會大幅增加，如幻燈片所示。

It is also important to note that the recent data that Toby mentioned showed that reducing tau expression was associated with favorable trends on clinical outcomes and pathological tau as measured by PET imaging. We view these data as supportive for a knockdown approach and believe that the one-time IV gene therapy could provide benefits over repeated [physical] therapy.

同樣值得注意的是，托比提到的最新數據表明，降低 tau 表達與臨床結果和 PET 成像測量的病理 tau 的良好趨勢相關。我們認為這些數據支持敲除方法，並相信一次性靜脈基因治療比重複[物理]治療更有益處。

This program remains on track for US IND and Health Canada CTA filings in 2026. I will now turn the call back over to Al.

該計劃仍有望在 2026 年完成美國 IND 和加拿大衛生部 CTA 申請。我現在將電話轉回給 Al。

Thanks, Todd. As you can see on slide 11, there continues to deliver on expectations for 2024. We have advanced the pipeline, our platform, and our partnerships. Our strong cash position of $345 million at the end of the third quarter is expected to provide runway into 2027, enabling multiple data readouts. This cash figure doesn't include the recent payments from Novartis or Neurocrine, which were received in October, nor does it calculate any future potential milestones from our 14 partnered programs.

謝謝，托德。正如您在第 11 張投影片上看到的，我們繼續實現對 2024 年的期望。我們已經推進了通路、平台和合作夥伴關係。截至第三季末，我們的強勁現金狀況為 3.45 億美元，預計將為 2027 年提供支撐，實現多次數據讀取。該現金數字不包括 10 月收到的來自諾華或 Neurocrine 的最新付款，也不包括計算我們 14 個合作項目的任何未來潛在里程碑。

With a robust slate of clinical milestones expected into the next 12 to 24 months, a maturing partnership portfolio with top-tier collaborators and cash runway into 2027, we believe Voyager is poised to drive significant value creation over both the near and long term.

預計未來 12 至 24 個月內將實現一系列臨床里程碑，與頂級合作夥伴建立日趨成熟的合作夥伴關係，並擁有持續至 2027 年的現金流，我們相信 Voyager 將在近期和長期內推動實現重大價值創造。

Finally, I'd like to thank all of our employees for their hard work and dedication to improving the lives of patients. With that, we will open the call for questions.

最後，我要感謝我們所有員工為改善患者生活所付出的辛勤工作和奉獻精神。現在，我們將開始提問。

Thank you. At this time, we will conduct the question-and-answer session. (Operator Instructions)

謝謝。現在，我們將進行問答環節。（操作員指令）

(technical difficulty)

（技術難度）

Good afternoon. Thanks for taking our questions, and congrats on the progress. First, a follow-up to your comments on the tau PET imaging. We're curious whether you have more insight as to how to translate the tau PET imaging results like we saw from Roche's B into cognitive improvements. Any additional thoughts now that you've had a bit more time to let the CTAD data set in?

午安.感謝您回答我們的問題，並祝賀您的進展。首先，我會跟進您對 tau PET 成像的評論。我們很好奇，您是否對如何將羅氏 B 所見的 tau PET 成像結果轉化為認知改善有更多的見解。現在您有更多的時間來設定 CTAD 數據，還有其他想法嗎？

Do you think it's a question of selecting the right patients, selecting the right endpoint, and any thoughts on how to get that tau PET imaging data to translate into a clinical improvement and cognitive benefits?

您是否認為這是一個選擇正確的患者、選擇正確的終點的問題，以及如何將 tau PET 成像數據轉化為臨床改善和認知益處的想法？

So maybe I'll start that question, Toby. So I think fundamentally, I think that -- I'll reset the point that the -- where the tau PET imaging, we saw clear data in the whole population that you did not -- you slow the accumulation of tau.

所以也許我應該開始回答這個問題，托比。因此我認為從根本上來說，我認為——我將重新設定這一點——透過 tau PET 成像，我們在整個人群中看到了清晰的數據，而你沒有——你減緩了 tau 的積累。

And then I think the other point to make is that when you looked in some of the other populations, particularly the lower tau populations, you saw perhaps a slightly greater lesson of accumulation in that context. So do you think as we move forward, really understanding the population will be critical in the terms of perhaps tau burden, which seems to be the main point. And then I think the -- the other point I think is we'll look forward to understanding the full dose response in terms of sort of the tau reduction in the context of PK/PD. We look forward to that data from UCB moving forward. Those are my initial faults.

然後我認為要提出的另一點是，當你觀察一些其他種群，特別是 tau 含量較低的種群時，你可能會看到在這種背景下積累的教訓略多一些。那麼您是否認為，隨著我們不斷前進，真正了解人口對於 tau 負擔來說至關重要，這似乎是重點。然後我認為——另一點是，我們期待從 PK/PD 背景下 tau 減少的角度了解完整的劑量反應。我們期待 UCB 的數據能夠進一步進步。這些都是我最初的錯誤。

And I would just add that this relationship between how PET effects and disease effects on clinical outcomes are agnostic to the drug or to the approach, right? So there are more than one -- there's more than one drug-targeting tau over the next couple of years. I think we'll learn this relationship better, what degree of tau PET imaging translates to what clinical outcome. And I agree with Toby that selecting the right patients, particularly with respect to tau burden, for example, may be very important.

我只想補充一點，PET 效應和疾病對臨床結果的影響之間的關係與藥物或方法無關，對嗎？因此，未來幾年將有許多針對 tau 的藥物問世。我認為我們會更了解這種關係，什麼程度的 tau PET 成像會轉化為什麼樣的臨床結果。我同意托比的觀點，選擇正確的患者，特別是在 tau 負擔方面，可能非常重要。

Perfect. That's helpful. Then a follow-up on the SOD1 silencing gene therapy for ALS. You note in the press release in your prepared remarks that the initial trial could generate proof of concept based on biomarkers. Is that something that we could possibly see in 2026? Is that something that's within 12 months of the US IND?

完美的。這很有幫助。然後對 ALS 的 SOD1 沉默基因療法進行後續追蹤。您在新聞稿中準備好的發言中指出，初步試驗可以根據生物標記產生概念證明。我們在 2026 年有可能看到這種事情嗎？這是距離美國 IND 12 個月之內的事嗎？

So we haven't guided to timing of the biomarker results. The points I can make is that one will go into the silent population, of course, and two will start in -- populate in -- at doses with potentially applications given the severity of the disease. In that context, we do think results would be [reasonably brough up].

因此，我們沒有指導生物標誌物結果的時間。我可以指出的是，其中一種當然會進入沉默人群，另外兩種會根據疾病的嚴重程度，以可能應用的劑量開始進入人群。在這種情況下，我們確實認為結果將是[合理提出]。

And maybe I could add that certainly in the case of the person clinical development plan and the trials that have been published in the New England Journal, you can start to see effects on SOD1 levels in spinal fluid. And about -- is it 12 week?

也許我可以補充一點，在個人臨床發展計劃和《新英格蘭醫學雜誌》上發表的試驗中，您可以開始看到對脊髓液中 SOD1 水平的影響。大約是 12 週嗎？

12 weeks.

12 週。

And then effects on plasma neurofilament, which is a surrogate outcome that's reasonably likely to predict clinical outcomes and was the basis of approval by FDA of the person, that measurement should also yield data in the first say six months or so. So if that's any precedent, that gives you an idea of the timing that it takes to see both logical effect and the outcomes on clinically relevant surrogate outcomes like NFL.

然後對血漿神經絲的影響，這是一種替代結果，可以合理地預測臨床結果，也是 FDA 批准該人的基礎，該測量也應該在前六個月左右產生數據。因此，如果這是先例，那麼您就可以了解看到邏輯效果和臨床相關替代結果（如 NFL）的結果所需的時間。

That's very helpful. And last question, an accounting question from us. The $15 million from Novartis, the $3 million from Neurocrine, how will those be booked? Are those going to be booked in the fourth quarter of this year or will they be spread out over the life of those agreements?

這非常有幫助。最後一個問題，是我們的會計問題。諾華公司提供的 1500 萬美元和 Neurocrine 提供的 300 萬美元，這些資金將如何入帳？這些是否會在今年第四季預訂，還是會分散在這些協議的有效期內？

It will be booked in the fourth quarter.

將於第四季預訂。

Perfect. Thanks for taking our questions. Congrats again on the progress.

完美的。感謝您回答我們的問題。再次恭喜您的進展。

Jack Allen, Baird.

傑克艾倫、貝爾德。

Great. Thanks so much for taking the questions and congrats on the progress. I wanted to ask about an aspect of the Voyager story that's more in its infancy and that being the blood brain shuttle programs. I was hoping you could just provide some context as to where those programs sit and when you maybe you could look to bring an asset into the clinic. I know there's been a lot of activity in the space with AbbVie 's acquisition of Aliada and then also Roche providing some initial proof of concept data from their beta amyloid asset there as well.

偉大的。非常感謝您回答這些問題，並對所取得的進展表示祝賀。我想問一下航海家號故事中還處於起步階段的一個面向，就是血腦穿梭計畫。我希望您能提供一些背景信息，說明這些項目的進展情況，以及您何時可以考慮將資產引入診所。我知道這個領域有很多活動，AbbVie 收購了 Aliada，而羅氏也從他們的 β 澱粉樣蛋白資產中提供了一些初步的概念驗證數據。

Well, Jack, I'll start and I'll ask Todd to provide more color, but I would say that we're very excited about the potential of leveraging the receptors we identify through our capsid shuttle other macromolecules across the BBB. And as you pointed out, trontinemab -- the data with trontinemab, which leverages transparent receptor is looking very promising as an approach to get anti-amyloid antibodies into the brain.

好吧，傑克，我先開始了，我會讓托德提供更多的細節，但我想說的是，我們對利用我們通過衣殼穿梭於 BBB 中的其他大分子所識別的受體的潛力感到非常興奮。正如您所指出的，trontinemab —— 利用透明受體的 trontinemab 數據看起來非常有前景，可以作為一種將抗澱粉樣蛋白抗體注入大腦的方法。

And so we're very excited about that. We're still in the preclinical stages. We haven't been -- we're not close enough to the clinic yet to guide on when we would enter the clinic. Todd. Do you want to provide more color on that?

因此我們對此感到非常興奮。我們仍處於臨床前階段。我們還沒有去過——我們距離診所還不夠近，因此無法指導我們何時進入診所。托德。您想對此提供更多詳細資訊嗎？

Thanks, Al. So Jack, as you do point out, we are excited by it, and we know that these acceptors -- and we do have different receptors in different capsid families. They can mediate transcytosis or delivery across the blood brain barrier or a large molecule, the AAV capsid. So there's reason to believe that they should be able to deliver other things. But hopefully in the future, we'll be able to share data on that.

謝謝，艾爾。所以傑克，正如你所指出的，我們對此感到興奮，我們知道這些受體——我們在不同的衣殼家族中確實有不同的受體。它們可以介導跨血腦屏障或大分子 AAV 衣殼的轉胞吞或運送。因此有理由相信他們能夠實現其他目標。但希望未來我們能夠分享這方面的數據。

I think the other aspect is that we're seeing with receptors such as transferrin that there's the opportunity for additional receptors to have an impact, because we expect that each receptor could have its own profile, both for pharmacokinetics and safety that could really give an opportunity for different receptors for different diseases and indications.

我認為另一個方面是，我們看到，對於轉鐵蛋白等受體，其他受體也有可能產生影響，因為我們預計每種受體都有自己的特性，無論是藥物動力學還是安全性，這實際上可以為不同受體治療不同的疾病和適應症提供機會。

Great. That's great context. Maybe just one brief follow-up, you've been incredibly successful in partnering your gene therapy library of capsids, even in the context of these pre-clinical assets. Any comments as it relates to potential partnerships around the blood brain shuttle programs? And is that something you have an appetite for before moving this into the clinic?

偉大的。這是非常棒的背景。也許只是一個簡短的後續問題，您在合作衣殼基因治療庫方面取得了令人難以置信的成功，即使在這些臨床前資產的背景下。對血腦穿梭計畫的潛在合作有何評論？在將其應用於臨床之前，您是否對此有興趣？

Well, Jack. This is Al. Yeah, I'm always interested and willing to talk to potential partners. This is exactly the kind of thing where there could be expertise in other companies that could really be very complementary to our shuttle program. So always opening -- always open to talking to potential partners about these kinds of things and really accelerate the program.

好吧，傑克。這是艾爾。是的，我一直很感興趣並且願意與潛在的合作夥伴交談。這正是其他公司可以利用的專業知識，這些專業知識可以對我們的太空梭計畫起到很好的補充作用。因此，我們始終保持開放態度——始終願意與潛在合作夥伴討論這類事情，並真正加速該計劃的實施。

Joon Lee, Truist Securities.

Joon Lee，Truist Securities。

Hey. Congrats on the progress and thanks for taking our questions. Your plans for 7523 MAD study in 2025 imply that you may be -- maybe you've seen something positive in SAD study or am I being too liberal with my interpretation? And for the SAD study due in the first half of '25, in addition to safety, what are you tracking that could give us some incremental conviction on the drug? Thank you.

嘿。恭喜您的進展，並感謝您回答我們的問題。您對 2025 年 7523 MAD 研究的計劃是否意味著您可能——也許您在 SAD 研究中看到了一些積極的東西，或者我的解釋是否過於寬泛？對於將於 25 年上半年進行的 SAD 研究，除了安全性之外，您還在追蹤哪些因素可以讓我們對該藥物更有信心？謝謝。

Joon, this is Toby. Thank you for the question. Just to remind, the SAD study is in healthy volunteers. And so really the data we're looking from the SAD study is PK initially [in the just disease] and do we have the appropriate exposures to pick doses for the MAD study and some initial read on safety? So really, it's not a -- it's not in patient. That's the key point.

俊，這是托比。感謝您的提問。需要提醒的是，SAD 研究是在健康志願者中進行的。那麼，我們從 SAD 研究中看到的數據實際上最初是 PK（在單純的疾病中），我們是否有適當的暴露來為 MAD 研究選擇劑量以及一些關於安全性的初步讀數？所以實際上，它不是——它不是耐心的。這才是關鍵所在。

Jay Olson, Oppenheimer.

傑伊奧爾森、奧本海默。

Hey. Congrats on the progress and thanks for providing this update. We have a few questions. Based on the bepranemab data that you saw, what's your latest thinking on the potential read across to your own 7523 program? And is there any additional data from UCB that you would be interested in seeing? And then I have a follow-up.

嘿。恭喜您的進展並感謝您提供此更新。我們有幾個問題。根據您看到的 bepranemab 數據，您對於其對您自己的 7523 計劃的潛在影響有何最新想法？您是否有興趣查看 UCB 的其他數據？然後我有一個後續問題。

Well, look, I think -- Jay, this is Al. I mean, this is the first time we've seen that an antibody could have biological effects in the brain in humans, right? And so that's -- I look on that as positive, right, that an antibody approach could affect the biology of tau spreading in the brain.

嗯，看，我想──傑伊，這是艾爾。我的意思是，這是我們第一次看到抗體能夠對人類大腦產生生物效應，對嗎？所以 — — 我認為這是正面的，對吧，抗體方法可以影響 tau 在大腦中擴散的生物學。

Even before we knew about the bepranemab data, we did say that there could be readthrough, because we had tested the UCB antibody, which binds to a mid-domain region versus our antibody, which binds to the C-terminal region in an animal where we look for this -- we look at the spread of pathological tau in a mouse expressing human tau, where we inject pathological tau from Alzheimer's brains into the animal.

甚至在我們了解 bepranemab 數據之前，我們就說過可能會有讀通，因為我們已經測試了 UCB 抗體，它與中間結構域區域結合，而我們的抗體與動物的 C 末端區域結合，我們在那裡尋找這種抗體——我們觀察表達人類 tau 的小鼠中病理性 tau 的擴散，我們將來自阿茲海默症患者大腦的病理性 tau 體內。

And we said before the CTAD, before we knew anything about the bepranemab data that the UCB antibody was pretty comparable to our antibody in blocking the spread and actually distinguishable from the N-terminal-directed antibodies that did not block the spread in that same model and which also failed in the clinic. And so we still believe that there could be read-through, and we also expect that the safety perhaps would also be similar in the sense that the antibody is binding to extracellular tau.

在 CTAD 之前，在了解 bepranemab 的數據之前，我們說過，UCB 抗體在阻止擴散方面與我們的抗體相當，並且實際上可以與在同一模型中無法阻止擴散且在臨床上失敗的 N 端定向抗體區分開來。因此，我們仍然相信可能會有讀通現象，我們也預計，在抗體與細胞外 tau 結合的意義上，安全性也許也會相似。

I would say the other differentiating feature of our antibody relative to the UCB antibody is the fact that our antibody is specific for pathological forms of tau. We don't know how important that is; we'll find out. But that is another feature. So that's where we stand, Jay.

我想說，我們的抗體相對於 UCB 抗體的另一個區別特徵是我們的抗體針對病理形式的 tau 具有特異性。我們不知道這有多重要；我們會找到答案。但那是另一個特點。這就是我們的立場，傑伊。

Todd, do you want to add anything?

托德，你還有什麼要補充嗎？

I agree with everything you said, Al. The other thing to mention, there was a question about additional data from UCB, and I think it will be important for us to see what additional data come out on some of the PK and PD -- that PK/PD relationship.

我同意你說的一切，艾爾。另一件要提的事情是，有一個關於 UCB 的附加數據的問題，我認為，了解關於一些 PK 和 PD （即 PK/PD 關係）的附加數據對我們來說很重要。

As Al has pointed out, the relationship between reduction of tau accumulation and potential cognitive benefit that it appears is pretty interesting, and we see that as very encouraging. Those are in some groups. I think seeing more detail about target engagement and that relationship will really be important to interpret the results.

正如 Al 所指出的，減少 tau 累積和潛在的認知益處之間的關係似乎非常有趣，我們認為這非常令人鼓舞。這些都是屬於某些群體的。我認為了解目標參與度和這種關係的更多細節對於解釋結果非常重要。

Great. Thank you for that. And then maybe just as a follow-on, how are you thinking about prioritizing 7523 versus your tau-silencing gene therapy, and then the potential for combining either of your anti-tau approaches with anti-amyloid antibodies?

偉大的。謝謝你。然後也許只是作為後續問題，您如何考慮優先考慮 7523 與您的 tau 沉默基因療法，然後將您的抗 tau 方法與抗澱粉樣蛋白抗體相結合的可能性？

Well, I would say that they're both high priorities. Am I allowed to say that two things are both high priorities? And look, we've always said that tau was a pretty -- very important target that we think it's the next step in helping Alzheimer's patients that the anti-amyloid treatments got us started, but we need to do better for patients.

嗯，我想說它們都是高優先級的。我可以說有兩件事都是高度優先的嗎？我們一直說，tau 是一個非常重要的靶點，我們認為這是幫助阿茲海默症患者的下一步，抗澱粉樣蛋白治療是我們開始的，但我們需要為患者做得更好。

And so I think they're both high priorities. They're very different approaches in many ways. And so we'll find out which is the better approach.

因此我認為它們都是高度優先的。他們在許多方面採取了截然不同的方法。因此我們會找出哪種方法比較好。

In terms of combining or with the anti-amyloid antibodies, I do think that there could be a place for combining. I would say that it would be in those patients that seem to have a partial response to the anti-amyloid antibodies. If they have no response to the anti-amyloid antibodies, there's no sense in continuing the drug. If they've had a full response to anti-amyloid antibodies, which may be the case in some patients -- if you're not progressing or at all in your disease on anti-amyloid antibodies, there'd be no reason to add anything else.

就結合或與抗澱粉樣蛋白抗體而言，我確實認為可以有結合的空間。我想說的是，這些患者似乎對抗澱粉樣蛋白抗體有部分反應。如果他們對抗澱粉樣蛋白抗體沒有反應，繼續服用藥物就沒有意義了。如果患者對抗澱粉樣蛋白抗體產生了完全反應（某些患者可能確實如此），而如果您的抗澱粉樣蛋白抗體疾病沒有進展或根本沒有進展，那麼就沒有理由添加任何其他藥物。

So I think time will help us. Time will tell what the heterogeneity of the treatment response is to the anti-amyloid antibody therapies in humans as we see the drugs being rolled out. And then by the time we're ready to think about that combination approach, I think we'll have more data on how many patients respond fully, how many respond not at all and how many respond partially.

所以我認為時間會幫助我們。隨著藥物的推出，時間將告訴我們人類對抗澱粉樣蛋白抗體療法的治療反應的異質性。然後，當我們準備考慮這種組合療法時，我認為我們將獲得更多關於有多少患者完全有反應、有多少患者根本沒有反應以及有多少患者有部分反應的數據。

But I would say that we would want data initially as monotherapy too, first, to see that -- make sure that our drug is active and then have some understanding of the doses that we would want to use.

但我想說，我們最初也希望獲得單一療法的數據，首先要確保我們的藥物是有效的，然後了解我們想要使用的劑量。

Lili Nsongo, Leerink.

Lili Nsongo，Leerink。

Hi, good afternoon, and thank you for taking our question. So I guess the question for me. So the first one, as we await for in-patient data -- so in 2026 for the tau-targeted antibodies, are there any plans to potentially test previously developed C-terminal antibodies in preclinical models to try to further confirm the negative predictive values of the model you use in a more region-specific approach.

大家下午好，感謝您回答我們的問題。所以我想這個問題是針對我而言的。因此第一個問題，當我們等待住院數據時 - 對於 2026 年的 tau 靶向抗體，是否有計劃在臨床前模型中測試之前開發的 C 端抗體，以嘗試進一步確認您使用的模型的陰性預測值在更具區域針對性的方法中。

Well, if we -- if there's another neg antibody that's negative, I think that would be a pretty interesting study to do, particularly if it's not internal, right? So I'm not sure doing any more N-terminal-directed antibodies would add much. But if there's an antibody targeting a different epitope that fails, then it might be interesting to do that experiment that you're proposing, Lili.

好吧，如果我們 - 如果有另一個陰性抗體，我認為這將是一個非常有趣的研究，特別是如果它不是內部的，對嗎？所以我不確定再做任何 N 端定向抗體是否會有很大幫助。但是如果針對不同表位的抗體失敗了，那麼做你建議的那個實驗可能會很有趣，莉莉。

Yes, because it was my that both Hoffmann-La Roche and then Ljungberg had some see feature in [limbic antibody]. I think it could be really interesting technical data as we await.

是的，因為我認為 Hoffmann-La Roche 和 Ljunberg 都有一些共同點[邊緣抗體]。我認為這可能是我們所等待的非常有趣的技術數據。

And I guess maybe segue into my second question, so regarding the UCB data and the challenges that they've had in the overall population, would that compel you to potentially start the development in-patient in maybe a smaller, more targeted patient population? So I guess my question is, does the results of the study compel you to maybe have more stringent inclusion criteria in the initial in-patient study for the antibody?

我想這也許可以過渡到我的第二個問題，那麼關於 UCB 數據以及他們在總體人群中面臨的挑戰，這是否會迫使您在可能更小、更有針對性的患者群體中開始開發住院治療？所以我想我的問題是，研究結果是否迫使您在抗體的初始住院研究中建立更嚴格的納入標準？

Yeah. Hi, Lili. This is Al. And I'll start and I'll ask Toby to add his comments, but I would say that we would be very open to that idea. We would like to see if we can differentiate from bepranemab, if at all possible. And it could be that the choice of patient population could be a way to boost the efficacy that we see, particularly on the clinical outcome measures and get more clarity.

是的。你好，莉莉。這是艾爾。首先，我會請托比發表他的評論，但我想說，我們非常樂意接受這個想法。如果可能的話，我們想看看是否能夠將其與 bepranemab 區分開來。選擇患者族群可能是提高我們所看到的療效的一種方法，特別是在臨床結果測量方面，並獲得更清晰的結論。

Toby noted in his comments, there were sub-groups, particularly those that were pre-specified -- I think it was the APOE4 non-carrier, low-tau-burden patients who seem to do better. And those are exactly the patients where the effect on tau accumulation was more pronounced. So I'd be open to that.

托比在他的評論中指出，存在一些亞群體，特別是那些預先指定的亞群體——我認為 APOE4 非攜帶者、低 tau 負擔的患者似乎表現更好。而這些患者中 tau 累積的影響恰恰更為明顯。因此我對此持開放態度。

Even though it's a smaller population, we're talking about a gigantic population overall, the Alzheimer's disease patients and to have a targeted treatment for a smaller population that's still quite large, by the way, would be of interest. Toby?

儘管人數較少，但我們談論的是阿茲海默症患者總體數量龐大，因此針對這一較小但仍然相當龐大的人群進行有針對性的治療將會引起人們的興趣。托比？

So, I think, Al, you captured it nicely. I think the only other comment I'd make is that when we did look at the bepranemab data, they had segregated their low and high tau populations. There really weren't that many low tau patients in the study overall, about a 80-20 ratio approximately. And so I think more data there, that is suggestive data, but we look forward to the breakdown of those data.

所以，我認為，Al，你捕捉到了很好的效果。我認為我唯一要說的另一條評論是，當我們查看 bepranemab 數據時，他們已經將低 tau 和高 tau 群體分開。整體而言，研究中低 tau 患者的數量確實不多，大約是 80-20 的比例。因此我認為那裡有更多的數據，這是有啟發性的數據，但我們期待這些數據的細分。

Appreciate it. Maybe just a follow-up. So we will be waiting for initial safety and PK data in healthy volunteers in the first half of 2025. But I was wondering maybe if you could give a little more granularity in terms of when we should expect an update on the potential design of the in-patient study?

非常感謝。也許只是後續行動。因此，我們將等待 2025 年上半年健康志工的初步安全性和 PK 數據。但我想知道您是否可以提供更詳細的信息，說明我們何時可以獲得住院研究潛在設計的更新？

I think she's interested in the design of the multiple ascending dose study.

我認為她對多次遞增劑量研究的設計很感興趣。

Yes, thanks, Lili. So I think as we -- once we get closer to the start, which will start next year, we'll share the details of the design.

是的，謝謝，莉莉。所以我認為，一旦我們接近開始，也就是明年開始，我們就會分享設計的細節。

Patrick Trucchio, H.C. Wainwright & Co.

帕特里克·特魯基奧，H.C.溫賴特公司

Good afternoon. Thanks very much. Just a couple of questions for me. The first is just a follow-up on the earlier comment regarding the appropriate patient population for the tau program for the antibody program. Can you discuss what level of tau PET burden do you think could be appropriate of baseline based on this -- learnings from this recent data and particularly as we approach that Phase 1b trial with 7523.

午安.非常感謝。我只想問幾個問題。第一個只是先前關於抗體計劃的 tau 計劃適當患者人群的評論的後續。您能否基於從最新數據中了解到的情況，特別是當我們接近 7523 的 1b 期試驗時，討論一下您認為什麼水平的 tau PET 負擔適合基線。

And then separately as we think about or as we look ahead to the tau-silencing gene therapy, I'm wondering if you can talk about the advantages or differences we should expect from the tau-silencing gene therapy as compared to these tau-targeting antibodies.

然後，當我們分別思考或展望 tau 沉默基因療法時，我想知道您是否可以談談與這些 tau 靶向抗體相比，我們應該從 tau 沉默基因療法中期待哪些優勢或差異。

And then secondly, what remains to be completed to ensure that the 2026 IND and CTA filings remain on track for the tau-silencing gene therapy? And then lastly, if you could, just talk about the anticipated capsid and advantages of the Voyager platform as compared to some of these others in the field developing a similar approach?

其次，還有哪些工作要做，才能確保 2026 年 IND 和 CTA 申請能順利完成 tau 沉默基因療法？最後，如果可以的話，您能談談預期的 Voyager 平台的特點以及與該領域其他開發類似方法的平台相比的優勢嗎？

Well, that's a lot of questions, Patrick, but we'll knock them off one by one here. So I'll take the first one, and then maybe Toby can take the second. And Todd, you can take the third one.

好吧，帕特里克，問題有很多，但我們會在這裡一一解答。因此我會選擇第一個，然後也許托比可以選擇第二個。托德，你可以選擇第三個。

But anyway, on the appropriate patients, the cut off that UCB shared data with us was a pre-specified cutoff, but it was not the median. In fact, there were many fewer patients, I think, in the low tau burden subgroup versus the high tau. I think that was because it was pre-specified.

但無論如何，對於合適的患者，UCB 與我們共享資料的截止值是預先指定的截止值，但不是中位數。事實上，我認為，低 tau 負擔亞組的患者數量比高 tau 負擔亞組的患者數量要少得多。我認為那是因為它是預先指定的。

Hopefully, we'll see more data on the full range of tau burden. All we have is that one piece of data to go on. I think we would need more to be more specific about the tau burden. Toby, you can let me know if you disagree with that.

希望我們能夠看到有關 tau 負擔全方位的更多數據。我們擁有的只是那一份數據。我認為我們需要更具體地了解 tau 負擔。托比，如果你不同意的話，你可以告訴我。

Okay. And then on the tau KD, I think you were asking, how do we make sure that we stay like -- I'll be on track. And so maybe Toby and Todd, do you want to help me with those questions?

好的。然後關於 tau KD，我想你會問，我們如何確保我們保持——我會走在正軌上。那麼 Toby 和 Todd，你們願意幫我解答這些問題嗎？

So maybe I'll start and ask Todd to fill in. So the pre-clinical development is proceeding. I think the key next steps are sort of pivotal step of doing the toxicology studies.

因此也許我會開始並讓托德填寫。因此臨床前開發正在進行中。我認為接下來的關鍵步驟是進行毒理學研究的關鍵一步。

All right. So the standard ID-enabling studies would be part of the process. You also asked about differentiation for the tau knockdown versus the antibody approach, I believe. And I think the BIIB080 data, which is an ASO-delivered that has shown some really interesting clinical data to date versus the antibody approaches. But what we've seen in the BIIB080 data are not only signs that you could reduce the accumulation of tau, but you may be able to reduce tau burden -- pathological tau burden as measured by PET in some cases below starting burden, which is a pretty remarkable finding.

好的。因此，標準的 ID 支援研究將成為該過程的一部分。我相信您也詢問了 tau 敲除與抗體方法的差異。我認為 BIIB080 數據是由 ASO 提供的，與抗體方法相比，它迄今為止顯示出一些非常有趣的臨床數據。但是，我們在 BIIB080 數據中看到的不僅僅是可以減少 tau 積累的跡象，而且還可能能夠減輕 tau 負擔——在某些情況下，用 PET 測量的病理性 tau 負擔低於起始負擔，這是一個非常了不起的發現。

When you look at those sorts of data and even with the recent bepranemab data, that also seem to suggest that an impact on tau PET imaging results can impact clinically, I think there is a accumulating evidence in a clinical benefit with the gene therapy approach, of course.

當您查看這些數據，甚至是最近的 bepranemab 數據時，它們似乎也表明對 tau PET 成像結果的影響會對臨床產生影響，我認為，當然，有越來越多的證據表明基因治療方法具有臨床益處。

Here we're talking about a once and done approach. We can dose once. We know that our vectors -- and this gets into a little bit of the Voyager platform question as well -- that our capsids can deliver quite broadly throughout the CNS. We can get delivery not only to the -- I'll call it the shallower regions of the brain, but also the deeper structures with that single dose.

這裡我們討論的是一次完成的方法。我們可以服用一次。我們知道我們的載體——這也涉及旅行者平台的問題——我們的衣殼可以廣泛地運送到整個中樞神經系統。我們不僅可以將藥物輸送到——我稱之為大腦的較淺區域，而且可以透過單一劑量將藥物輸送到大腦的較深結構。

And so we think there could be some substantial benefits for a tau knockdown approach. It is also an intercellular effect. The antibody has an impact presumably based on the prion spreading hypothesis as the pathological tau spreads from cell to cell. So an intercellular reduction of tau could have an impact not only in reducing that cell-to-cell spread, but also in an intercellular way.

因此我們認為 tau 敲除方法可能會帶來一些實質的好處。這也是一種細胞間效應。抗體產生影響，大概是基於朊病毒擴散假說，因為病理性 tau 會在細胞之間擴散。因此，細胞間 tau 的減少不僅可以減少細胞間的傳播，還可以減少細胞間的傳播。

So those two approaches, I think, are both interesting. There are signs of for both those mechanisms that they could work. And in the end, it's even possible there could be combination approaches.

因此我認為這兩種方法都很有趣。有跡象表明這兩種機制都可以發揮作用。最後，甚至有可能採用組合方法。

So Toby, do you want to add on potential clinical outcomes?

那麼托比，你想補充一下潛在的臨床結果嗎？

So there, I think the BIIB080 data, in particular, really emphasized along with the recent bepranemab data, the importance of tau PET. And to Todd's PowerPoint in the BIIB080 knockdown-based approach or a knockdown-based approach, you can see the removal of both pre-existing pathological tau and prevention of further accumulation and in somewhat earlier timeframes, six months or so, which is distinct from slowing accumulation. This is particular to the tau knockdown approach.

因此，我認為 BIIB080 數據與最近的 bepranemab 數據一起特別強調了 tau PET 的重要性。在 Todd 的 PowerPoint 中，透過基於 BIIB080 敲低的方法或基於敲低的方法，您可以看到預先存在的病理性 tau 被去除，並且進一步積累被防止，並且在稍早的時間範圍內，大約六個月，這與減緩積累不同。這對於 tau 敲除方法來說尤其如此。

In addition, you can also see clear signals in the CSF biomarkers. And so there is a chance based on biomarkers to get a relative quick read on how the molecule is performing.

此外，您還可以在腦脊髓液生物標記中看到清晰的訊號。因此，我們有機會根據生物標記相對快速地了解分子的性能。

And what about the -- do you think the effect size? I mean, it's hard --

那麼—您認為效果如何？我的意思是，這很難--

It's early data that the -- I mean, if you look at the propensity score matching that Biogen performed, they looked at a comparison to other study called TANGO, they looked at the natural history study and there, that effect size was 2 to 2.5 points on CDR sum of boxes as a reminder of the effects on the [amyloid] 0.4 to 0.9 points what's approximately on CDR sum of boxes. So potentially, larger effect size as well, which gives you an additional opportunity to potentially (technical difficulty) signal with smaller sample size.

這是早期數據 — — 我的意思是，如果你看看 Biogen 所進行的傾向得分匹配，他們會將其與另一項名為 TANGO 的研究進行比較，他們還會查看自然歷史研究，並且會發現效果大小在 CDR 框總和上為 2 到 2.5 分，這提醒我們，對 [澱粉樣蛋白] 的效果在 CDR 框上大約為 0.4 到總完成。因此，潛在的效果尺寸也更大，這為您提供了額外的機會（技術難度）以較小的樣本量發出訊號。

I'm showing no further questions at this time. I would now like to turn it back to Al for closing remarks.

我目前沒有其他問題。現在我想請 Al 作最後發言。

Thank you, everyone, for joining us today, and we look forward to speaking with you again soon.

感謝大家今天的加入我們，我們期待很快能再次與你們交談。

Thank you for your participation in today's conference. This does include the program. You may now disconnect.

感謝大家參加今天的會議。這確實包括該程式。您現在可以斷開連線。