(BIIB) 2023 Q3 法說會逐字稿

Good morning. My name is Ali, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen Third Quarter 2023 Earnings Call and Business Update. (Operator Instructions) Today's conference is being recorded. Thank you.

早安.我叫阿里，今天我將擔任你們的會議操作員。此時，我謹歡迎大家參加百健 (Biogen) 2023 年第三季財報電話會議和業務更新。 （操作員指示）今天的會議正在錄音。謝謝。

I would now like to turn the conference over to Mr. Chuck Triano, Head of Investor Relations. Mr. Triano, you may begin your conference.

現在我想將會議交給投資者關係主管查克·特里亞諾 (Chuck Triano) 先生。特里亞諾先生，您可以開始會議了。

Thank you, Ali. Good morning, and welcome to Biogen's Third Quarter 2023 Earnings Call. Before we begin, I'll remind you that the earnings release and related financial tables, including our GAAP financial measures and a reconciliation of the GAAP to non-GAAP financial measures that we will discuss today are located in the Investors section of biogen.com. Our GAAP financials are provided in Tables 1 and 2, and Table 4 includes a reconciliation of our GAAP to non-GAAP financial results. We believe non-GAAP financial results better represent the ongoing economics of our business and reflect how we manage the business internally. We have also posted slides on our website that follow the discussion related to this call.

謝謝你，阿里。早安，歡迎參加百健 (Biogen) 2023 年第三季財報電話會議。在我們開始之前，我要提醒您，收益發布和相關財務表格，包括我們今天將討論的 GAAP 財務指標以及 GAAP 與非 GAAP 財務指標的調整表，位於 biogen.com 的投資者部分。表 1 和表 2 提供了我們的 GAAP 財務數據，表 4 包括我們的 GAAP 與非 GAAP 財務結果的調整表。我們相信非公認會計準則財務績效更能代表了我們業務的持續經濟狀況，並反映了我們內部管理業務的方式。我們也在我們的網站上發布了與本次電話會議相關的討論的幻燈片。

I'd like to point out that we will be making forward-looking statements, which are based on our expectations. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail.

我想指出的是，我們將根據我們的預期做出前瞻性陳述。這些陳述存在一定的風險和不確定性，我們的實際結果可能有重大差異。我鼓勵您查閱我們向 SEC 提交的文件中討論的風險因素，以了解更多詳細資訊。

So on today's call, I am joined by our President and Chief Executive Officer, Chris Viehbacher; Dr. Priya Singhal, Head of Development; and our CFO, Mike McDonnell. Chris, Priya and Mike will each make some opening comments, and then we'll move to a Q&A session, and to allow us to get through as many questions as possible, we kindly ask that you limit yourself to one question.

我們的總裁兼執行長 Chris Viehbacher 也參加了今天的電話會議。 Priya Singhal 博士，開發主管；和我們的財務長麥克麥克唐納。 Chris、Priya 和 Mike 將分別發表一些開場評論，然後我們將進入問答環節，為了讓我們能夠回答盡可能多的問題，我們懇請您將自己限制在一個問題上。

I'll now turn the call over to Chris.

我現在將把電話轉給克里斯。

Thank you very much, Chuck. Good morning, all. I think we released a very good set of results this morning ahead of expectations. But of course, we're all too consciously aware that really what most of you are interested in is where is Biogen going?

非常感謝你，查克。大家早安。我認為我們今天早上發布了一組非常好的結果，超出了預期。但當然，我們都非常清楚地知道，你們大多數人真正感興趣的是百健（Biogen）將走向何方？

To that end, we outlined 5 priorities that we believe we needed to achieve to put Biogen in a position to be able to grow again sustainably. And I think in the first 9 months of the year, we've made an awful lot of progress. And indeed, I would say the third quarter was a particularly busy quarter.

為此，我們概述了我們認為需要實現的 5 個優先事項，以使 Biogen 能夠再次實現永續成長。我認為今年前 9 個月，我們取得了很大進展。事實上，我想說第三季是一個特別繁忙的季度。

To remind you all what those priorities were really was to focus our teams and our resources on new product launches. And that is a little easier said than done. We're a company that has a long heritage in the treatment of multiple sclerosis. And teams get very passionate about patient outcomes and working with physicians, and to move them to new areas does require a concerted effort.

為了提醒大家這些優先事項的真正意義是將我們的團隊和資源集中在新產品的發布上。這說來容易做來難。我們是一家在多發性硬化症治療方面擁有悠久歷史的公司。團隊對患者的治療結果以及與醫生的合作充滿熱情，將他們轉移到新的領域確實需要共同努力。

The other thing we want to do is to stabilize and grow again those existing products that still have market exclusivity for a significant period of time, notably VUMERITY and SPINRAZA.

我們想做的另一件事是穩定並再次成長那些在相當長一段時間內仍具有市場獨佔性的現有產品，特別是 VUMERITY 和 SPINRAZA。

The third thing was to really look at our cost base. Although we had a relatively mature product portfolio, we had -- one of the higher OpEx to sales ratios in our -- among our peer group, and we needed to address that. But more than that, we needed to really reallocate our resources.

第三件事是真正檢視我們的成本基礎。儘管我們擁有相對成熟的產品組合，但我們是同業中營運支出與銷售比率較高的公司之一，我們需要解決這個問題。但更重要的是，我們需要真正重新分配我們的資源。

Fourth was to really look at our research and development pipeline, particularly for the longer-term growth outlook. We have really taken a deep dive into research and development, looked at those products -- projects that perhaps no longer fulfilled their original target product profile where the practice of medicine has changed, where the probability of success had changed, and we have terminated those programs so that we can focus on those assets that we think have the most promise. And I think we have a number of those, any one of which could actually meaningfully add to our longer-term growth.

第四是真正檢視我們的研發管道，特別是長期成長前景。我們確實深入研究和開發，研究了這些產品——這些項目可能不再滿足其最初的目標產品概況，其中醫學實踐已經改變，成功的可能性已經改變，我們已經終止了這些項目計劃，以便我們能夠專注於那些我們認為最有希望的資產。我認為我們有很多這些，其中任何一項實際上都可以有意義地促進我們的長期成長。

And then the final thing was we said right at the outset, we were interested in external growth. We always knew that the LEQEMBI launch was going to be a gradual launch. We always knew that also even the zuranolone launch was a nonconventional launch. And to derisk that profile, we wanted to look at external growth. And of course, we've been able to do that.

最後一件事是我們一開始就說過，我們對外部成長感興趣。我們一直都知道 LEQEMBI 的發布將是一個漸進的發布。我們一直都知道，即​​使是 zuranolone 的推出也是非常規的推出。為了消除這種情況的風險，我們希望專注於外部成長。當然，我們已經能夠做到這一點。

So as I look at where we are in the third quarter, we actually had LEQEMBI was the first anti-amyloid antibody to receive traditional approval for early Alzheimer's disease. ZURZUVAE was a mixed bag. We got an important indication with postpartum depression. But of course, we missed on the major depressive disorder. As expected, we received schedule IV listing from the DEA, and we also had QALSODY approved for treating a genetic cause of ALS. This is not necessarily a product that is going to be of interest to many of you from the revenue potential, but scientifically, this is a major milestone and validating the biomarker neurofilament, I think will enable so many researchers to find further treatments for ALS and perhaps other diseases.

因此，當我觀察第三季度的情況時，我們實際上發現 LEQEMBI 是第一個獲得傳統批准用於早期阿茲海默症的抗澱粉樣蛋白抗體。 ZURZUVAE 是一個混合體。我們得到了產後憂鬱症的重要跡象。但當然，我們錯過了重度憂鬱症。正如預期的那樣，我們收到了 DEA 的附表 IV 清單，並且 QALSODY 也被批准用於治療遺傳性 ALS。從收入潛力來看，這不一定是你們許多人感興趣的產品，但從科學角度來看，這是一個重要的里程碑，驗證了生物標記神經絲，我認為這將使許多研究人員能夠找到針對ALS 和ALS 的進一步治療方法。也許還有其他疾病。

As I noted, we closed the acquisition of Reata Pharmaceuticals, and that gives us a whole new growth opportunity. SKYCLARYS is off to a very strong launch, and we'll talk about that in a minute. But it also builds out our rare disease portfolio. As you know, we are trying to move into some adjacencies, just given the risk of the neurological conditions that we have tended to focus on, and rare diseases has been a logical place for us to go.

正如我所指出的，我們完成了對 Reata Pharmaceuticals 的收購，這給了我們一個全新的成長機會。 SKYCLARYS 即將推出，我們稍後會討論這一點。但它也建構了我們的罕見疾病組合。如您所知，考慮到我們傾向於關注的神經系統疾病的風險，我們正在嘗試進入一些鄰近領域，而罕見疾病一直是我們的合理選擇。

Biogen has been very successful with the launch of SPINRAZA, and we think we can do the same with SKYCLARYS. And as I mentioned earlier, we had the Fit for Growth program. And this wasn't just about cost reduction, because we do want to reinvest some of that, but we really needed to simplify the organizational structure to empower the organization more and move more of the decision-making closer to markets and customers. We have ended up taking an entire layer enterprise-wide out of the organization and in some parts of the organization, even 2 layers of that.

百健（Biogen）公司透過 SPINRAZA 的推出取得了非常成功，我們認為我們也可以在 SKYCLARYS 上做到同樣的事情。正如我之前提到的，我們有「適合成長」計畫。這不僅僅是為了降低成本，因為我們確實想對其中的一些進行再投資，但我們確實需要簡化組織結構，以賦予組織更多權力，並使更多決策更貼近市場和客戶。我們最終在整個企業範圍內從組織中取消了整個層，在組織的某些部分，甚至是其中的兩層。

So we do think those cost savings will add meaningfully to our earnings per share as we look forward. But I'm also looking forward to a significant change culturally in how we allocate capital and the agility and ability to take decisions in the organization. Could I move to the next slide, please?

因此，我們確實認為，未來這些成本節省將顯著增加我們的每股盈餘。但我也期待在我們如何分配資本以及在組織中做出決策的敏捷性和能力方面發生重大文化變革。我可以轉到下一張投影片嗎？

So let's talk about LEQEMBI. Subject, I'm sure all of you are very interested in. We have always guided that this was going to be a gradual launch. And we know that partly from the ADUHELM experience, but also just from the fundamentals of what we're doing.

那我們來談談 LEQEMBI。我相信大家都很感興趣。我們一直認為這會是個逐步推出的過程。我們知道這一點部分來自 ADUHELM 的經驗，但也來自我們正在做的事情的基本原理。

This is a product that needs to be administered within a treatment process or care network. And those care networks did not exist at the time of the launch. So they have to be built, and doing that requires actually quite a significant change to the work patterns within clinics. And while IDNs and clinics are working really hard to put these in place, it, of course, takes time. And I think a terrific example of that is the announcement recently by the Cleveland Clinic.

這是一種需要在治療過程或護理網絡中管理的產品。這些護理網絡在推出時並不存在。因此必須建造它們，而要做到這一點實際上需要對診所內的工作模式進行相當大的改變。儘管 IDN 和診所正在努力將這些落實到位，但這當然需要時間。我認為克利夫蘭診所最近宣布的一個很好的例子。

We all know that the Cleveland Clinic is one of the most widely respected medical centers anywhere in the world, and they recently announced that they had just infused their first patient with LEQEMBI, months after the approval. And I think that just speaks to the complexity that we're dealing with. And in a lot of ways, we not only are pioneering science, we're pioneering this commercial approach.

我們都知道克利夫蘭診所是世界上最受尊敬的醫療中心之一，他們最近宣布，在獲得批准幾個月後，他們剛剛為第一位患者註射了 LEQEMBI。我認為這恰恰說明了我們正在處理的複雜性。在很多方面，我們不僅開創了科學，也開創了這種商業方法。

So of course, we have an aim of getting to 10,000 patients by the end of March. We're at 800 now. What gives us the confidence that we think we can get there? Well, I think we have a number of green shoots here, signs of progress. The first is, as we look at our internal metrics of intent to treat and patient demand, we are seeing all of those things progress extremely nicely.

當然，我們的目標是在 3 月底之前覆蓋 10,000 名患者。我們現在是800。是什麼讓我們有信心相信我們能夠實現這一目標？嗯，我認為我們已經出現了一些新芽，進步的跡象。首先，當我們查看治療意圖和患者需求的內部指標時，我們看到所有這些事情都進展得非常好。

The FDA not only provided traditional approval, but EMS actually moved very quickly. The day of traditional approval, as they promised, they actually have provided reimbursement, and the patient registry has so far from what we hear from the market has been relatively easy to use.

FDA不僅提供傳統的批准，而且EMS實際上行動得非常快。在傳統審批當天，正如他們所承諾的那樣，他們實際上已經提供了報銷，而且病患登記系統到目前為止與我們從市場上聽到的情況相比相對容易使用。

We had some confusion around the reimbursement of amyloid PET and CMS has clarified that. Now of course, it's going to take a little time for that to flow down through to the MAX. But I think that will also relieve some of the confusion out there.

我們對澱粉樣蛋白 PET 的報銷有些困惑，CMS 已經澄清了這一點。當然，現在需要一些時間才能流到 MAX。但我認為這也會緩解一些混亂。

I think one of the most interesting things is we've got 60% of the top 100 targeted IDNs now having P&T approval. One of the things that really gives me a lot of inspiration is usually, these P&T committees meet twice a year, but a number of them actually have organized special meetings just for LEQEMBI and not wait until the next meeting. And that says to me that there's a recognition of the importance of this treatment and being able to get patients on treatment.

我認為最有趣的事情之一是，前 100 個目標 IDN 中的 60% 現在已獲得 P&T 批准。真正給我很大啟發的一件事是，這些 P&T 委員會通常每年召開兩次會議，但其中一些委員會實際上專門為 LEQEMBI 組織了特別會議，而不是等到下一次會議。這對我來說意味著人們認識到這種治療的重要性以及能夠讓患者接受治療的重要性。

So where we also go from here, remember, a year from -- a year ago from here, there were still skepticism about whether reducing amyloid plaque would really have a benefit. And it wasn't really until the CLARITY study was finally presented at CTAD last year, that we really have, for the first time, clear compelling evidence of the benefit of removing these amyloid plaques.

因此，請記住，從現在開始，一年前，人們仍然懷疑減少澱粉樣蛋白斑是否真的有好處。直到去年 CLARITY 研究最終在 CTAD 上發表，我們才真正第一次獲得了明確、令人信服的證據，證明去除這些澱粉樣蛋白斑塊的益處。

And now, of course, we can go and say, "All right, that's tremendous. But why is that so? Well, for years, we've been trying to develop antibodies, and those antibodies failed. And that was -- that's what gave rise to the skepticism, which were the right patients, which was the right antibody that was going to get the right amount of drug into the brain. And LEQEMBI is really the first one to show that clear compelling evidence that, that has occurred.

當然，現在我們可以說：「好吧，這太棒了。但為什麼會這樣呢？多年來，我們一直在嘗試開發抗體，但這些抗體失敗了。那就是——那就是什麼引起了懷疑，哪些是正確的患者，哪些是正確的抗體，可以將適量的藥物注射到大腦中。而LEQEMBI 確實是第一個證明這種情況已經發生的明確令人信服的證據的人。

Now of course, we don't want to get fancy. And that's where we're going. And we just had CTAD this year and think about what we've just done. We are generating more data to really demonstrate the benefit of this treatment. We've seen, for instance, that the subcutaneous treatment is going to work, that we have comparability with the infusion. And this means so much for the convenience of patients.

當然，現在我們不想變得花哨。這就是我們要去的地方。今年我們剛剛召開了 CTAD，並思考我們剛剛做了什麼。我們正在產生更多數據來真正證明這種治療的好處。例如，我們已經看到皮下治療會起作用，我們與輸液具有可比性。這對患者的便利來說意義重大。

But this is no mean task either. Others have tried to do this. How do you get enough drug through the muscle tissue and into the brain? That has been achieved and is a major milestone. We've been looking at maintenance dosing. What happens when you've cleared the plaque? Does the plaque come back? Well, we have 24 months data now that shows a lot of benefit of staying on treatment.

但這也不是一項艱鉅的任務。其他人已經嘗試這樣做。如何讓足夠的藥物通過肌肉組織進入大腦？這已經實現，並且是一個重要的里程碑。我們一直在研究維持劑量。清除牙菌斑後會發生什麼事？牌匾還能回來嗎？嗯，我們現在有 24 個月的數據，顯示堅持治療有很多好處。

Then the question is still who's the right patient? And data were shown with early -- with early stage patients with low levels of tau. And those are fascinating data. We had 76% of those patients stable over the course of measurement, and very intriguing and very interesting, we actually saw with 60% of those patients that we actually saw some clinical benefit as measured by the CDR sum of boxes, completely unexpected that generated an awful lot of discussion at CTAD.

那麼問題仍然是誰是合適的患者？數據顯示，早期患者的 tau 蛋白量較低。這些都是令人著迷的數據。我們有76% 的患者在測量過程中保持穩定，非常有趣，我們實際上看到其中60% 的患者確實看到了一些臨床獲益（透過CDR 框架總和來衡量），完全出乎意料的是，這產生了CTAD 上進行了大量討論。

So now, of course, we're also looking at executing on geographic expansion. We've had the recent approval of Japan, and I'm traveling to Japan early in the new year to be with my friend and colleague, the CEO of Eisai to launch LEQEMBI in Japan. And of course, we've got global filings under review in the EU, China and 10 other markets. So this is one where we're going to have to be patient, but all the signs are green at this moment. And for us internally, we see a launch that is on track. But as we've always said, there's no real analogs. And every month, we learn something new. If I could move to the next slide, please, Chuck.

當然，現在我們也在考慮執行地域擴張。我們最近獲得了日本的批准，新年伊始我將前往日本，與我的朋友兼同事、衛材 (Eisai) 首席執行官一起在日本推出 LEQEMBI。當然，我們已經在歐盟、中國和其他 10 個市場接受了全球申請的審查。因此，我們必須要有耐心，但目前所有跡像都是綠色的。對於我們內部來說，我們看到產品的發布正在按計劃進行。但正如我們常說的，沒有真正的類似物。每個月我們都會學到一些新東西。請讓我轉到下一張投影片，查克。

Now let's talk about SKYCLARYS, something that is much different. And as you know, we now have 1,180 start forms to date, with about 860 patients actually on drug. When we look at all of the known analogs, we're actually exceeding all of those, including SPINRAZA at the same point in time.

現在讓我們來談談 SKYCLARYS，這是一個非常不同的東西。如您所知，迄今為止我們已有 1,180 份起始表格，其中約 860 名患者實際上正在接受藥物治療。當我們查看所有已知的類似物時，我們實際上超越了所有這些，包括同一時間點的 SPINRAZA。

Now we have to be a little cautious, because we all know that there would likely have been a number of patients ready and waiting by physicians. And I think that was even more of the case because you may recall that the product was actually approved in the spring, but then delayed for a couple of months due to a technical and temporary challenge on supply. And so I think it was an anticipation.

現在我們必須有點謹慎，因為我們都知道可能有很多病人已經準備好等待醫生。我認為情況更是如此，因為您可能還記得該產品實際上是在春季獲得批准的，但後來由於技術和供應方面的臨時挑戰而推遲了幾個月。所以我認為這是一種預期。

Nonetheless, there is a very strong desire to see this product come, and we're actually seeing a lot of requests from countries around the world to make SKYCLARYS available. And that just speaks to, I think, the understanding that this is the very first treatment that has ever been approved for Friedreich's ataxia. This is an incredibly debilitating disease that affects so many young people right in the prime of their life. And so it's extremely important that they benefit from that. We had about $43 million of sales in the third quarter.

儘管如此，人們還是非常渴望看到這款產品的問世，而且我們實際上看到了來自世界各國的大量請求，要求提供 SKYCLARYS。我認為，這只是說明了一種理解，即這是第一個被批准用於弗里德賴希共濟失調的治療方法。這是一種令人難以置信的使人衰弱的疾病，影響著許多正值青春年華的年輕人。因此，讓他們從中受益非常重要。第三季我們的銷售額約為 4,300 萬美元。

One of the things that we are now working on, and I think this is where Biogen can really add value is, why is there 1,180 on start forms and 860 on the drug? Well, there are a number of things, trying to get reimbursement, we need genetic tests, we need to measure your liver enzymes before you go on the product.

我們現在正在研究的事情之一，我認為這就是百健（Biogen）真正可以增加價值的地方，為什麼起始表格上有 1,180 個字，而藥物上有 860 個字？嗯，有很多事情，試圖獲得報銷，我們需要基因測試，我們需要在您使用該產品之前測量您的肝臟酵素。

And one of the differences from SPINRAZA is that they're not all incentives. They could be out there in primary care physician care. And the Biogen is well equipped to do that. We are used to providing genetic tests, we don't worry about the reimbursement, we provide those. We have mobile labs so that we can help patients who are not near to major medical centers to get, for instance, the lab implants done.

與 SPINAZA 的區別之一是它們並不都是激勵措施。他們可能會參與初級保健醫生的照護。百健 (Biogen) 完全有能力做到這一點。我們習慣於提供基因檢測，我們不擔心報銷，我們提供那些。我們擁有行動實驗室，這樣我們就可以幫助那些不靠近主要醫療中心的患者完成實驗室植入等工作。

And also, we know how to pull through these start forms and navigate the difficult reimbursement situation. So I think not only is there an advantage for Biogen in getting this important medicine to patients around the world. But I think even in the United States, we can actually make this more rapidly available to patients.

而且，我們知道如何完成這些啟動表格並應對困難的報銷情況。因此，我認為百健（Biogen）不僅在向世界各地的患者提供這種重要藥物方面具有優勢。但我認為即使在美國，我們實際上也可以更快地為患者提供這種服務。

So with that, I'll turn it over to Priya.

那麼，我會把它交給 Priya。

Thank you, Chris. This was an exciting quarter for Biogen's development organization, with the approval of ZURZUVAE in postpartum depression, as well as important new data presented for LEQEMBI and our tau-targeting ASO, BIIB080. Two programs we believe that are critical to expanding Biogen's leadership in Alzheimer's disease.

謝謝你，克里斯。對於百健 (Biogen) 的開發組織來說，這是一個令人興奮的季度，ZURZUVAE 治療產後憂鬱症獲得批准，以及 LEQEMBI 和我們的 tau 靶向 ASO BIIB080 的重要新數據。我們認為這兩個計畫對於擴大百健（Biogen）在阿茲海默症領域的領導地位至關重要。

Starting with LEQEMBI, at CTAD last month, Eisai presented new data on a subcutaneous formulation of LEQEMBI. We believe the interim results at 6 months showed that subcutaneous LEQEMBI was comparable to the IV formulation on the basis of drug exposure as assessed by area under the drug as well as plaque -- amyloid plaque removal.

從 LEQEMBI 開始，衛材在上個月的 CTAD 上展示了 LEQEMBI 皮下製劑的新數據。我們相信 6 個月的中期結果表明，根據藥物暴露以及斑塊（澱粉樣斑塊去除）評估的藥物暴露，皮下 LEQEMBI 與 IV 製劑相當。

In terms of safety, we believe the timing, frequency and severity of ARIA-E was similar across IV and subcutaneous formulations. Additionally, overall, the incidence rate of systemic reactions with subcutaneous LEQEMBI was also lower with mild symptoms as compared to first-time LEQEMBI IV-treated patients from the CLARITY AD Core Study.

在安全性方面，我們認為 ARIA-E 的時間、頻率和嚴重程度在靜脈注射和皮下注射製劑中是相似的。此外，整體而言，與 CLARITY AD 核心研究中首次接受 LEQEMBI IV 治療的患者相比，皮下注射 LEQEMBI 的全身反應發生率也較低，且症狀較輕。

We believe these results further support the intent to develop subcutaneous formulation of LEQEMBI and if approved, may allow for greater patient access, improved compliance and convenience.

我們相信這些結果進一步支持了開發 LEQEMBI 皮下製劑的意圖，如果獲得批准，可能會允許更多的患者使用，提高依從性和便利性。

We've made significant progress in our understanding of the potential clinical benefit that is associated with amyloid removal in Alzheimer's disease. However, there's still very many key questions remaining on how to maximize the clinical benefit with these agents, including when to begin treatment.

我們在了解阿茲海默症中澱粉樣蛋白去除相關的潛在臨床益處方面取得了重大進展。然而，如何最大限度地提高這些藥物的臨床效益，包括何時開始治療，仍有許多關鍵問題。

We believe the differentiated and straightforward design of the CLARITY AD study, allowing entry of Alzheimer's patients with confirmed amyloid pathology but low tau burden, allows us to gain additional insights into the clinical profile of LEQEMBI across various stages of Alzheimer's disease.

我們相信，CLARITY AD 研究的差異化和直接設計，允許進入已確診澱粉樣蛋白病理學但tau 負荷較低的阿茲海默症患者，使我們能夠進一步了解LEQEMBI 在阿茲海默症各個階段的臨床概況。

The data show that in the low tau subpopulation, which represents the earliest stages of early AD, 76% of patients showed no decline and 60% showed clinical improvement at 18 months, as assessed by CDR sum of boxes compared to 55% and 28% for placebo, respectively. We are very encouraged by these results.

數據顯示，在代表早期AD 最早階段的低tau 亞群中，根據CDR 框架總和評估，76% 的患者在18 個月時沒有出現任何衰退，60% 的患者表現出臨床改善，而這一比例為55% 和28%分別為安慰劑。我們對這些結果感到非常鼓舞。

A second key question for the field is what happens when you continue treating after amyloid plaques have been removed, and why would this be beneficial? We believe that dual-acting LEQEMBI continues to support brain neuron function by also removing soluble highly toxic protofibrils that can cause neuronal injury and death even after plaque removal. Therefore, with LEQEMBI, we believe there is a potential for longer-term treatment to sustain or further the clinical benefit observed within the initial plaque removal phase.

該領域的第二個關鍵問題是，當澱粉樣蛋白斑塊被去除後繼續治療時會發生什麼，為什麼這會是有益的？我們相信，雙重作用的 LEQEMBI 還可以去除可溶性高毒性原纖維，從而繼續支持腦神經元功能，即使在斑塊移除後，這些原纖維也可能導致神經元損傷和死亡。因此，對於 LEQEMBI，我們相信長期治療有可能維持或進一步在初始斑塊移除階段觀察到的臨床益處。

In terms of data supporting this potential benefit, when examining the 24-month data from the CLARITY AD Core Study and the open-label extension, we see a potential clinical benefit from continuing to treat with LEQEMBI. Specifically, the separation in CDR sum of boxes between the group that continued to receive LEQEMBI or the early start group, and the group who switched from placebo to LEQEMBI, the delayed start group was maintained during the 6-month open-label extension following the core study, suggesting a disease-modifying effect.

就支持此潛在益處的數據而言，在檢查 CLARITY AD 核心研究和開放標籤擴展的 24 個月數據時，我們看到繼續使用 LEQEMBI 治療具有潛在的臨床益處。具體而言，繼續接受 LEQEMBI 或早期開始組與從安慰劑轉為 LEQEMBI 的組（延遲開始組）之間的 CDR 總和分離在治療後 6 個月的開放標籤延伸期間保持不變。核心研究表明具有緩解疾病的作用。

The clinical benefit observed in the early start group at 24 months is further supported by the comparison against participants from the ADME observational natural history cohort that was selected to match the baseline demographics and clinical characteristics of the CLARITY AD population.

與 ADME 觀察性自然史隊列的參與者進行比較進一步支持了在 24 個月時早期開始組中觀察到的臨床益處，該隊列是為了匹配 CLARITY AD 人群的基線人口統計和臨床特徵而選擇的。

Additionally, while the delayed start LEQEMBI cohort does not catch up to the early start group, we do believe a potential slowing of decline with 6 months of LEQEMBI treatment as compared to the ADME cohort at the 24-month time point.

此外，雖然延遲開始 LEQEMBI 隊列沒有趕上早期開始組，但我們確實相信，與 24 個月時間點的 ADME 隊列相比，6 個月的 LEQEMBI 治療可能會減緩下降速度。

We believe the totality of these data support both the importance of initiating treatment early, as well as the durability of effect observed with continued LEQEMBI treatment.

我們相信，這些數據的整體支持了早期開始治療的重要性，以及持續 LEQEMBI 治療觀察到的效果的持久性。

As we aim to provide options for patients, Eisai is currently evaluating maintenance dosing or every 4-week LEQEMBI dosing after the removal of plaque and plans to submit a regulatory filing by the end of Q1 2024.

由於我們的目標是為患者提供選擇，衛材目前正在評估維持劑量或去除牙菌斑後每 4 週 LEQEMBI 劑量，併計劃在 2024 年第一季末提交監管文件。

Also at CTAD, Biogen presented new data from the Phase Ib study of our antisense oligonucleotide targeting tau. In the new results in this small study for patients treated with the 2 highest doses of BIIB080, we observed favorable trends on multiple exploratory end points of cognition and function as assessed by the CDR sum of boxes, MMSE and Functional Activities Questionnaire, when compared to the baseline matched external controls at week 100. These findings build upon previously reported results from the BIIB080 Phase Ib, showing strong target engagement in the CSF and a reduction in the brain tau pathology as measured by Tau-PET.

同樣在 CTAD 上，百健 (Biogen) 展示了我們針對 tau 的反義寡核苷酸 Ib 期研究的新數據。在這項針對接受 2 個最高劑量 BIIB080 治療的患者的小型研究的新結果中，我們觀察到透過 CDR 框架總和、MMSE 和功能活動問卷評估的認知和功能多個探索性終點的有利趨勢，與基線與第100 週時的外部對照相匹配。這些發現建立在先前報告的BIIB080 Ib 期結果的基礎上，顯示CSF 中的強大目標參與以及透過Tau-PET 測量的腦tau 病理學的減少。

Biomarker data from the placebo-controlled period and long-term extension phase of this study were just recently published in JAMA Neurology. Viewed as an underlying pathology of Alzheimer's disease, tau has long been an area of focus in Alzheimer's drug development. While many prior attempts using monoclonal antibodies have failed, we now see from the Phase Ib study of an (inaudible) a convergence of evidence across soluble biomarkers, tau PET and exploratory clinical measures, suggesting a link between the reduction in tau pathology and potential clinical benefit.

這項研究的安慰劑對照期和長期延伸期的生物標記數據最近剛發表在《JAMA Neurology》雜誌上。 tau 蛋白被視為阿茲海默症的潛在病理學，長期以來一直是阿茲海默症藥物開發的重點領域。雖然之前許多使用單株抗體的嘗試都失敗了，但我們現在從一項（聽不清）可溶性生物標記、tau PET 和探索性臨床測量證據的Ib 期研究中看到，這表明tau 病理學的減少和潛在的臨床治療之間存在關聯。益處。

As a reminder, our tau targeting ASO is a completely new mechanism, which unlike the antibodies is designed to reduce production of all forms of tau, including both intracellular and extracellular species.

提醒一下，我們的 tau 蛋白靶向 ASO 是一種全新的機制，與抗體不同，它旨在減少所有形式 tau 蛋白的產生，包括細胞內和細胞外種類。

One clear challenge that we saw with antibodies was their inability to target intracellular species. We believe these results, while early, are encouraging, and we are excited to be enrolling the Phase II CELIA study of BIIB080 in early AD.

我們看到抗體面臨的一個明顯挑戰是它們無法靶向細胞內物種。我們相信這些結果雖然早期，但令人鼓舞，我們很高興能夠在 AD 早期參與 BIIB080 的 II 期 CELIA 研究。

Over the last few months, I have spoken about our efforts to reprioritize Biogen's development pipeline in an effort to optimize R&D value and productivity. This presented us with an opportunity to take a fresh look at our pipeline, and identify areas where we believe we have both sufficient expertise and confidence in the science as well as our ability to deliver meaningful new treatments to patients while prioritizing resources accordingly.

在過去的幾個月裡，我談到了我們為重新調整百健（Biogen）開發管道的優先順序所做的努力，以優化研發價值和生產力。這為我們提供了一個機會，讓我們重新審視我們的產品線，並確定我們相信我們在科學上擁有足夠專業知識和信心的領域，以及我們有能力為患者提供有意義的新療法，同時相應地優先考慮資源的領域。

This starts with Alzheimer's, where we believe we have demonstrated scientific leadership and are taking steps to build long-term impact. This includes, first, working with Eisai on several initiatives aimed at differentiating LEQEMBI and providing options to patients.

首先是阿茲海默症，我們相信我們已經展現了科學領導力，並採取措施建立長期影響。首先，這包括與衛材合作進行多項旨在區分 LEQEMBI 並為患者提供選擇的措施。

Second, continuing to advance our ASO targeting tau, as well as preclinical programs that span different molecular targets and approaches across the Alzheimer's disease biology.

其次，繼續推進我們針對 tau 的 ASO，以及涵蓋阿茲海默症生物學不同分子標靶和方法的臨床前項目。

Lastly, continuing to deliver new insights on Alzheimer's disease biology and long-term treatment with anti-amyloid antibodies.

最後，繼續提供阿茲海默症生物學和抗澱粉樣蛋白抗體長期治療的新見解。

On this point, at CTAD, we also presented new data from aducanumab, including new data from the EMERGE long-term extension and the EMBARK redosing study. We believe these findings can help support the field's understanding of the potential long-term treatment benefits associated with anti-amyloid antibodies.

在這一點上，在 CTAD 上，我們也展示了 aducanumab 的新數據，包括 EMERGE 長期擴展和 EMBARK 重劑量研究的新數據。我們相信這些發現可以幫助支持該領域對與抗澱粉樣蛋白抗體相關的潛在長期治療益處的理解。

Beyond Alzheimer's disease, we have multiple near-term inflection points across various programs and therapeutic areas over the next year. This includes regulatory outcomes for LEQEMBI in several geographies as well as regulatory outcomes for other products.

除了阿茲海默症之外，明年我們的各個計畫和治療領域還將出現多個近期轉折點。這包括 LEQEMBI 在多個地區的監管結果以及其他產品的監管結果。

In addition, we have important readouts for BIIB105 in ALS, BIIB121 in Angelman syndrome and dapirolizumab pegol in SLE, all expected midyear 2024.

此外，我們還獲得了治療 ALS 的 BIIB105、治療 Angelman 綜合徵的 BIIB121 以及治療 SLE 的達匹羅利珠單抗（dapirolizumab pegol）的重要數據，預計將於 2024 年年中發布。

Combined with the long-term potential of programs like litifilimab, our homegrown assets currently being evaluated in 2 Phase III studies for SLE and a Phase II/III study for CLE, we believe our pipeline has the potential to support Biogen's return to sustainable growth. And with our partners on the research and business development teams, we continue to evaluate external opportunities.

結合litifilimab等計畫的長期潛力，我們的本土資產目前正在兩項針對SLE的III期研究和一項針對CLE的II/III期研究中進行評估，我們相信我們的產品線有潛力支持Biogen恢復可持續增長。我們與研究和業務開發團隊的合作夥伴一起繼續評估外部機會。

I will now pass the call over to Mike.

我現在將把電話轉給麥克。

Thank you, Priya. Good morning, everyone. I'm going to provide some highlights and color regarding our financial performance for the third quarter of 2023, and all the financial comparisons that you'll hear are versus the third quarter of 2022.

謝謝你，普里亞。大家，早安。我將提供有關我們 2023 年第三季財務業績的一些亮點和色彩，以及您將聽到的所有財務比較都是與 2022 年第三季的比較。

Total revenue for the third quarter was $2.5 billion. That's an increase of 1% at actual currency and 3% at constant currency. Non-GAAP diluted EPS in the third quarter was $4.36.

第三季總營收為25億美元。以實際貨幣計算成長 1%，以固定貨幣計算成長 3%。第三季非 GAAP 攤薄後每股收益為 4.36 美元。

Total MS product revenue was $1.2 billion. That's a decrease of 14% at actual currency and 12% at constant currency. And that decline is primarily attributable to generic entrants for TECFIDERA as well as broad competition in the MS market.

MS 產品總收入為 12 億美元。以實際貨幣計算下降 14%，以固定匯率計算下降 12%。這種下降主要歸因於 TECFIDERA 的仿製藥進入以及 MS 市場的廣泛競爭。

I would like to provide a few updates to the MS business this quarter. First, in Europe, we continue to see that some generics have not yet fully exited some of the EU markets, and we do believe that there may still be some generic product remaining in the channel. The pace of generic withdrawal has been slower than we expected, but we continue to closely monitor the situation and are working to enforce our legal rights to market protection.

我想提供本季度 MS 業務的一些最新情況。首先，在歐洲，我們繼續看到一些仿製藥尚未完全退出部分歐盟市場，我們確實相信可能仍有一些仿製藥產品留在通路中。仿製藥撤回的步伐比我們預期的要慢，但我們將繼續密切關注事態發展，並努力執行我們的市場保護合法權利。

TYSABRI biosimilar was approved in the U.S. and EU, which we had previously assumed. At this point, we are not expecting a launch this year, but we are aware that there are plans to launch a biosimilar in the first half of 2024. Biogen still has patents relating to TYSABRI and we will continue to enforce our IP.

我們先前假設，TYSABRI 生物相似藥已在美國和歐盟獲得批准。目前，我們預計不會在今年推出，但我們知道計劃在 2024 年上半年推出生物相似藥。百健 (Biogen) 仍擁有 TYSABRI 相關專利，我們將繼續執行我們的智慧財產權。

VUMERITY was a bright spot in the third quarter. We did see revenue increase 20%, and that was driven primarily by global patient growth. However, we are seeing continued effects from both pricing pressure and an overall contraction of the oral segment of the market in the United States.

VUMERITY 是第三季的亮點。我們確實看到收入成長了 20%，這主要是由全球患者成長推動的。然而，我們看到價格壓力和美國口腔市場整體收縮的持續影響。

Next, Global SPINRAZA revenue of $448 million increased 4% at actual currency and 7% at constant currency. The 7% growth that we saw included 7% growth in the U.S. as well, and that was driven by patient growth, while outside the U.S., SPINRAZA benefited from the timing of shipments in certain markets.

其次，SPINRAZA 全球營收為 4.48 億美元，以實際貨幣計算成長 4%，以固定匯率計算成長 7%。我們看到的 7% 的增長也包括美國 7% 的增長，這是由患者增長推動的，而在美國之外，SPINRAZA 受益於某些市場的發貨時機。

We continue to be encouraged by the performance of SPINRAZA in the past few quarters and continue to believe that we're making good progress against our goal of returning SPINRAZA to consistent growth over time.

我們繼續對 SPINRAZA 在過去幾個季度的表現感到鼓舞，並繼續相信我們正在朝著使 SPINRAZA 隨著時間的推移恢復持續增長的目標取得良好進展。

Biosimilars. The third quarter revenue of $194 million, increased 4% at actual currency and 7% at constant currency.

生物相似藥。第三季營收為 1.94 億美元，以實際貨幣計算成長 4%，以固定匯率計算成長 7%。

During the third quarter, we updated how we present commercialization expenses incurred within the LEQEMBI collaboration. Our 50% portion of LEQEMBI net product revenue and cost of sales which includes royalties will continue to be classified as a component of revenue. Now Biogen's 50% share of all global commercialization sales and marketing expenses for the LEQEMBI collaboration will be presented in the SG&A expense line and will no longer be presented as a reduction to revenue.

在第三季度，我們更新了 LEQEMBI 合作中產生的商業化費用的列報方式。我們 LEQEMBI 淨產品收入和銷售成本（包括特許權使用費）的 50% 部分將繼續歸類為收入的組成部分。現在，百健 (Biogen) 在 LEQEMBI 合作的所有全球商業化銷售和行銷費用中所佔的 50% 份額將計入 SG&A 費用項目，而不再作為收入減少列示。

During the third quarter of 2023, we reclassified approximately $39 million of commercial collaboration costs from the first and second quarters of 2023 to reflect this change in presentation. These costs were moved out of the revenue line and into the SG&A expense line, resulting in a $39 million increase to both revenue and SG&A for the third quarter, with no bottom line impact.

在 2023 年第三季度，我們對 2023 年第一季和第二季約 3,900 萬美元的商業合作成本進行了重新分類，以反映列報方式的這種變化。這些成本從收入線轉移到 SG&A 支出線，導致第三季的收入和 SG&A 增加了 3,900 萬美元，但沒有對底線產生影響。

This change in presentation does not affect any of our agreements with Eisai, and we continue to share LEQEMBI collaboration revenue and commercialization expenses 50-50. This change will allow us to be more transparent in our reporting and it's consistent with how some others in our industry report collaborations. This change will have no impact to Biogen's bottom line.

這種表述方式的變化不會影響我們與衛材的任何協議，我們將繼續以 50-50 的比例分享 LEQEMBI 合作收入和商業化費用。這項變更將使我們的報告更加透明，並且與我們行業中其他一些人報告合作的方式一致。這項變更不會對百健（Biogen）的利潤產生影響。

As Eisai reported in-market product revenue for LEQEMBI in the third quarter was approximately $2 million. Our anti-CD20 revenue was $421 million, and that included an $11 million operating loss related to LUNSUMIO.

根據衛材報告，第三季 LEQEMBI 的市場產品收入約為 200 萬美元。我們的抗 CD20 收入為 4.21 億美元，其中包括與 LUNSUMIO 相關的 1,100 萬美元營運虧損。

Contract manufacturing royalty and other revenue of $304 million was notably higher year-over-year, and that was driven mainly by the timing of batches, and it also includes the reclassified $39 million, which I just mentioned.

合約製造特許權使用費和其他收入為 3.04 億美元，同比顯著增加，這主要是由批次時間推動的，其中還包括我剛才提到的重新分類的 3900 萬美元。

A couple of things to note regarding the third quarter expenses. Third quarter non-GAAP cost of sales was 26% of total revenue, and that includes $35 million of idle capacity charges. Cost of sales as a percentage of revenue continues to be impacted by product mix and in particular, this quarter, increases in contract manufacturing revenue.

關於第三季支出需要注意的幾點。第三季非 GAAP 銷售成本佔總收入的 26%，其中包括 3,500 萬美元的閒置產能費用。銷售成本佔收入的百分比持續受到產品組合的影響，特別是本季合約製造收入成長的影響。

Third quarter non-GAAP R&D expense includes approximately $44 million related to our portion of the LEQEMBI collaboration, and approximately $37 million in closeout costs related to the EMBARK trial for ADUHELM.

第三季非公認會計原則研發費用包括與我們的 LEQEMBI 合作部分相關的約 4,400 萬美元，以及與 ADUHELM 的 EMBARK 試驗相關的約 3,700 萬美元的收尾成本。

Third quarter non-GAAP SG&A expense includes approximately $82 million related to our portion of the LEQEMBI collaboration, and that includes the previously mentioned reclassification of $39 million in collaboration costs from the first and second quarters of 2023 from revenue to SG&A expense.

第三季非GAAP SG&A 費用包括與我們LEQEMBI 合作部分相關的約8,200 萬美元，其中包括先前提到的從2023 年第一季和第二季開始將3,900 萬美元的合作成本從收入重新分類為SG&A費用。

As compared to the prior year, the decrease in third quarter non-GAAP SG&A expense was driven by approximately $100 million in cost savings initiative, partially offset by an increase in commercialization expense for LEQEMBI and ZURZUVAE as well as the $39 million reclassification that I just mentioned.

與前一年相比，第三季度非GAAP SG&A 費用的減少是由約1 億美元的成本節約計劃推動的，部分被LEQEMBI 和ZURZUVAE 的商業化費用的增加以及我剛剛提到的3900 萬美元的重新分類所抵消。提及。

Next, a few brief comments on our balance sheet. We ended the quarter with $2.3 billion in cash and marketable securities and $7.3 billion in debt, and that puts us in a net debt position of approximately $5 billion. Even though these figures include the majority of the payments related to the close of the Reata transaction, it is important to note that we expect to utilize an additional approximately $1.3 billion of cash for outstanding payment obligations related to the transaction, and that should occur in the fourth quarter. We do continue to generate steady positive cash flow from operations and generated $518 million of free cash flow during the third quarter.

接下來，對我們的資產負債表進行一些簡短的評論。本季結束時，我們擁有 23 億美元的現金和有價證券以及 73 億美元的債務，這使我們的淨債務部位約為 50 億美元。儘管這些數字包括與 Reata 交易結束相關的大部分付款，但值得注意的是，我們預計將額外使用約 13 億美元的現金來支付與交易相關的未償付款義務，這應該發生在第四季度。我們確實繼續從營運中產生穩定的正現金流，並在第三季產生了 5.18 億美元的自由現金流。

In the coming quarters, we will be utilizing a portion of our cash flow to pay down some of the newly acquired $1 billion of short-term debt that we used to partially fund the Reata transaction.

在接下來的幾個季度中，我們將利用部分現金流來償還新收購的 10 億美元短期債務中的一部分，這些債務是我們用於為 Reata 交易提供部分資金的。

And next, I'd like to provide an update to our full year 2023 financial guidance, which takes into consideration 3 key recent events. One is the completed acquisition of Reata. Second is the regulatory approval for ZURZUVAE in postpartum depression. And the third is the modification that we made to our presentation of the LEQEMBI expenses.

接下來，我想提供 2023 年全年財務指引的更新，其中考慮了最近發生的 3 個關鍵事件。一是完成對Reata的收購。其次是 ZURZUVAE 治療產後憂鬱症的監管批准。第三是我們對 LEQEMBI 費用的列報進行的修改。

We're updating our full year 2023 revenue guidance to a low-single-digit percentage decline, and that is an improvement from our previous guidance, which was a mid-single-digit decline. And that's, of course, compared to full year 2022 reported results. This is primarily driven by the update to how we present LEQEMBI commercial expenses, which are no longer presented as a reduction to revenue.

我們將 2023 年全年收入指引更新為低個位數百分比下降，這比我們先前的指引（中個位數下降）有所改善。當然，這是與 2022 年全年報告的結果相比。這主要是由於我們更新了 LEQEMBI 商業費用的呈現方式，這些費用不再作為收入的減少呈現。

We are also updating and narrowing our full year 2023 non-GAAP diluted earnings per share guidance to be between $14.50 and $15. As we have previously noted, the acquisition of Reata will be slightly dilutive to our 2023 non-GAAP EPS, with an expected impact of approximately $0.75. Much of this impact comes from financing the transaction, which affects our operating income and expense line, including incremental interest expense, a significant decrease in interest income. Absent this impact from the Reata transaction, our EPS guidance would be narrowed to $15.25 to $15.75 and that's consistent with the midpoint of our previous guidance.

我們也將更新 2023 年全年非 GAAP 攤薄每股收益指引，並將其縮小至 14.50 美元至 15 美元之間。正如我們之前指出的，收購 Reata 將略微稀釋我們 2023 年非 GAAP 每股收益，預計影響約為 0.75 美元。這種影響很大一部分來自於融資交易，這影響了我們的營業收入和支出線，包括增量利息支出，利息收入大幅下降。如果沒有 Reata 交易的影響，我們的 EPS 指導將縮小至 15.25 美元至 15.75 美元，這與我們先前指導的中點一致。

Further, for 2023, we expect some incremental OpEx associated with the Reata acquisition, and that will be largely offset by decreased spending for ZURZUVAE as we prepare to launch in the PPD indication. We also expect some savings from our Fit for Growth program in 2023.

此外，到 2023 年，我們預計與 Reata 收購相關的營運支出將會增加，而隨著我們準備在 PPD 適應症中推出，這將在很大程度上被 ZURZUVAE 支出的減少所抵消。我們也預計 2023 年我們的 Fit for Growth 計畫將節省一些費用。

Looking forward to 2024, it is very important to note that as a result of the Reata transaction, we will have approximately $6 billion less in cash that was generating interest income at approximately 5%, as well as an incremental $1 billion in debt at a blended rate of approximately 6.7%.

展望 2024 年，值得注意的是，由於 Reata 交易，我們將減少約 60 億美元的現金，而這些現金產生的利息收入約為 5%，且債務增加了 10 億美元。混合率約為6.7%。

I'd also note that for the full year 2023, we've absorbed a headwind of approximately $0.30 to EPS due to currency fluctuations, and this is a dynamic that we're watching very closely for 2024. I'd offer that we estimate every $0.01 change in the euro versus the U.S. dollar has a roughly $18 million impact to our P&L. I'd also refer you to our press release for other important guidance assumptions.

我還想指出的是，在 2023 年全年，由於貨幣波動，我們的每股收益承受了約 0.30 美元的逆風，這是我們正在密切關注的 2024 年動態。我建議我們估計歐元兌美元匯率每變動0.01 美元，就會對我們的損益產生約1800 萬美元的影響。我還建議您參閱我們的新聞稿，以了解其他重要的指導假設。

Finally, a brief update on our Fit for Growth cost savings initiatives. I'd start by reiterating that the program maintains the target of approximately $1 billion in gross savings by 2025 as compared to full year 2023. Since we first announced the program, we have not made any changes to our planned level of reinvestment other than the acquisition of Reata and the regulatory approval for ZURZUVAE in PPD-only, neither of which were included in our original assumption.

最後，簡要介紹我們的「適合成長」成本節約計畫的最新情況。首先我要重申，與 2023 年全年相比，該計劃維持了到 2025 年總節省約 10 億美元的目標。自我們首次宣布該計劃以來，除了收購Reata 以及監管部門批准ZURZUVAE 僅用於PPD，這兩者都不包含在我們最初的假設中。

The expected impact of Reata and ZURZUVAE to the original program is approximately a net decrease in the expected reinvestment of $100 million, or said differently, we now expect an additional $100 million in net savings. So the original $700 million in expected net savings increases to approximately $800 million.

Reata 和 ZURZUVAE 對原始計畫的預期影響大約是預期再投資淨減少 1 億美元，或者換句話說，我們現在預計淨節省將增加 1 億美元。因此，最初預計的 7 億美元淨節省增加到約 8 億美元。

I would also just highlight that these figures do not include the impact of the LEQEMBI commercial spend, which will now be reflected in our SG&A line and will, of course, continue to ramp up as commercial activity and sales increase.

我還想強調的是，這些數字不包括 LEQEMBI 商業支出的影響，這些支出現在將反映在我們的 SG&A 項目中，當然會隨著商業活動和銷售的增加而繼續增加。

I'd also like to point out that as before, the expense estimates presented today did not contemplate any incremental business development or any transactions related to the biosimilars business, and they assume continued R&D spend on ADUHELM through at least 2025.

我還想指出，與之前一樣，今天提出的費用估算並未考慮任何增量業務開發或與生物仿製藥業務相關的任何交易，並且他們假設 ADUHELM 的研發支出至少持續到 2025 年。

I'm going to now turn the call back to Chris for some closing remarks.

我現在將把電話轉回給克里斯，讓他做一些結束語。

Thank you, Mike. So we're already into 2024 in our AOP planning. And as we look to next year, we actually have a number of milestones, which is nice to see.

謝謝你，麥克。因此，我們的 AOP 規劃已進入 2024 年。展望明年，我們實際上有許多里程碑，這是很高興看到的。

As I mentioned earlier, we have an EMA decision on LEQEMBI in the EU and in China. We'll have a decision on SKYCLARYS in the EU and QALSODY in the EU, all in the first half of next year. We intend to have 2 more important regulatory submissions, one for the subcu formulation and also for the IV maintenance dosing, both for LEQEMBI. And then finally, we're actually starting to see some development readouts in the pipeline. We expect dapirolizumab Phase III in SLE in the new year. We have our ASO for sporadic ALS, reading out on a Phase I/II, Phase I in Angelman syndrome. And of course, with Sage, the SAGE-324 program in the essential tremor. So I think we'll have a number of interesting news points for next year.

正如我之前提到的，我們對歐盟和中國的 LEQEMBI 做出了 EMA 決定。我們將在明年上半年就歐盟的 SKYCLARYS 和歐盟的 QALSODY 做出決定。我們打算提交兩份更重要的監管申請，一份針對 subcu 製劑，另一份針對 IV 維持劑量，皆針對 LEQEMBI。最後，我們實際上開始看到一些正在醞釀中的開發成果。我們預計達匹羅珠單抗治療 SLE 的 III 期臨床試驗將在新的一年進行。我們有針對散發性 ALS 的 ASO，讀出 Angelman 症候群的 I/II 期、I 期。當然，還有 Sage、特發性震顫中的 SAGE-324 程序。所以我認為明年我們將會有一些有趣的新聞點。

And with that, Chuck, I think we can turn it over for questions.

查克，我想我們可以把它轉過來提問了。

Thank you, Chris. Ali, can we please poll for questions?

謝謝你，克里斯。 Ali，我們可以投票提問嗎？

(Operator Instructions) And our first question comes from the line of Salveen Richter with Goldman Sachs.

（操作員說明）我們的第一個問題來自高盛的薩爾文·里克特（Salveen Richter）。

Just on the Reata assets here, now with the acquisition closed and the launch progressing well, could you just give us your thoughts around key near-term value drivers, including the launch trajectory, the EMA approval outlook for early next year and then expansion into the pediatric population?

就這裡的 Reata 資產而言，現在收購已完成，啟動進展順利，您能否向我們介紹一下您對近期關鍵價值驅動因素的看法，包括啟動軌跡、明年初 EMA 批准前景以及隨後擴展到兒科人群？

Right. So when -- actually, when you look at SPINRAZA. SPINRAZA is a good analog. One of the nice things about the rare disease space is that we tend not to be so U.S.-centric. So when you look at SPINRAZA sales, it's broadly, not quite, but it's roughly 1/3, 1/3, 1/3 between the U.S., EU and then the international area. And we expect the same really for SKYCLARYS.

正確的。所以當——實際上，當你看到《斯賓拉莎》。 SPINRAZA 是一個很好的類比。罕見疾病領域的好處之一是我們往往不那麼以美國為中心。所以當你看一下 SPINRAZA 的銷售時，你會發現它的銷量很寬泛，但不完全是，但大約是美國、歐盟和國際地區的 1/3、1/3、1/3。我們對 SKYCLARYS 也抱持相同的期望。

So we do expect significant value to come out of both EU but also in Latin America, perhaps some in the Middle East, Turkey. Obviously, for genetic reasons, there is none in the Asia region. But we do know that there are quite a few patients, for instance, in Brazil and in Argentina. So we are accelerating our efforts to file for approval in Latin America.

因此，我們確實預期歐盟和拉丁美洲（也許還有中東和土耳其）都會產生巨大的價值。顯然，由於遺傳原因，亞洲地區沒有。但我們確實知道，例如在巴西和阿根廷，有相當多的患者。因此，我們正在加緊努力在拉丁美洲申請批准。

On the EU, you never want to try to predict entirely the regulators. They have to respect their ability to make a decision until the end. But everything we've seen so far doesn't really change anything in our view of the probability of this being approved in the EU. And that represented, if you may remember at the time of the transaction, we estimate about 1/3 of the value of the transaction.

在歐盟，你永遠不想嘗試完全預測監管機構。他們必須尊重自己做出決定的能力，直到最後。但到目前為止，我們所看到的一切並沒有真正改變我們對歐盟批准法案的可能性的看法。如果您還記得交易時的情況，這表示我們估計交易價值的 1/3 左右。

And then the pediatric study, we are in discussion with regulators. That will be actually quite important, because there are a number of patients who start to become diagnosed as early as 5 or 6 years old, but certainly in that 8- to 10-year-old time frame. So it's quite important that we get the pediatric study underway.

然後是兒科研究，我們正在與監管機構進行討論。這實際上非常重要，因為有許多患者早在 5 或 6 歲時就開始被診斷出來，但肯定是在 8 到 10 歲的時間範圍內。因此，我們進行兒科研究非常重要。

Thank you, Chris. Can we move to our next question, please?

謝謝你，克里斯。我們可以轉到下一個問題嗎？

And our next question comes from Brian Abrahams from RBC Capital.

我們的下一個問題來自 RBC Capital 的 Brian Abrahams。

I'm not hearing you, Brian.

我沒聽見你說話，布萊恩。

We move on next to Geoff Meacham from Bank of America.

我們繼續前行，旁邊是美國銀行的傑夫‧米查姆 (Geoff Meacham)。

Just had one on LEQEMBI maintenance. When we think about the strategy, I guess the question is, do you have regulatory color on a separate maintenance claim, just given the emphasis on plaque reduction initially? And related to that, would there have to be an initial level of evidence when you think about maintenance for -- with respect to CMS reimbursement?

剛剛進行了 LEQEMBI 維護。當我們考慮該策略時，我想問題是，考慮到最初強調減少牙菌斑，您是否對單獨的維護索賠有監管色彩？與此相關的是，當您考慮 CMS 報銷的維護時，是否必須有初步證據？

I'll pass that one, Geoff, to Priya.

傑夫，我會把那個交給普莉亞。

Thank you, Geoff. With regards to maintenance, what I can tell you is that Eisai has communicated that as you know, we are testing it every 4 weeks. This is with the intravenous infusion. And this data is expected to be filed by Q1 2024. I won't be able to comment on what it would lead to in terms of indication and such, but we are preparing the data for a potential filing.

謝謝你，傑夫。關於維護，我可以告訴您的是，衛材已表示，如您所知，我們每 4 週進行一次測試。這是靜脈輸液。該數據預計將於 2024 年第一季提交。我無法評論它會在指示等方面產生什麼結果，但我們正在為潛在的提交準備數據。

Thanks, Priya. Next question please, operator.

謝謝，普里亞。接線員，請下一個問題。

And next, we'll go back to Brian Abrahams with RBC Capital Markets.

接下來，我們將回到加拿大皇家銀行資本市場部門的布萊恩亞伯拉罕斯 (Brian Abrahams)。

Can you hear me now?

你聽得到我嗎？

Yes, we can, Brian.

是的，我們可以，布萊恩。

Okay. Sorry, I don't know what happened there before. Congrats on all the progress. So coming out of CTAD on subcu LEQEMBI. I realize FDA discussions are still to be had there. Can you -- can you maybe help us understand your latest thinking as to what's likely to be required for approval? How much, if any, additional patient data do you think you might need to generate at the dose you might go forward with, might you expect to be able to file for a lower dose based on PK modeling? And maybe you could confirm whether additional patients you're still seeing flows through the trials there are still seeing exposure below the 125% upper bound?

好的。抱歉，我不知道之前發生了什麼事。祝賀所有的進步。所以從 CTAD 上的 subcu LEQEMBI 出來。我意識到 FDA 的討論仍有待進行。您能否幫助我們了解您對批准可能需要哪些內容的最新想法？您認為在您可能繼續使用的劑量下可能需要產生多少（如果有）額外的患者數據，您是否希望能夠根據 PK 模型申請較低的劑量？也許您可以確認您仍在接診的其他患者在進行試驗時是否仍看到暴露低於 125% 上限？

Did you get all that, Priya?

你明白了嗎，普里亞？

Yes. Thank you, Brian. So this is really -- we are encouraged with the subcutaneous interim data that we shared and Eisai shared at CTAD. Just stepping back, the subcutaneous study was a sub-study in the open-label extension for CLARITY AD. The patient population that was treatment naive and where we were really assessing the PK/PD, which is the PK parameters as well as the PD outcome of amyloid plaque reduction was a subset of 72 patients. And in addition, the study was set up to gather safety and tolerability in an additional 324 subjects. So the total study population was 394.

是的。謝謝你，布萊恩。所以這確實是——我們和衛材在 CTAD 上分享的皮下中期數據讓我們深受鼓舞。退一步來說，皮下研究是 CLARITY AD 開放標籤擴展的子研究。未接受治療且我們真正評估 PK/PD（即 PK 參數以及澱粉樣斑塊減少的 PD 結果）的患者群體是 72 名患者的子集。此外，研究的目的是收集另外 324 名受試者的安全性和耐受性。因此，研究總人數為 394 人。

And what we shared was that we believe that the subcutaneous formulation showed comparability and bioequivalents with the intravenous formulation. And it was between the confidence intervals of 80% and 120% -- and 125% of exposure.

我們分享的是，我們相信皮下製劑與靜脈注射製劑具有可比性和生物等效性。它的置信區間介於 80% 和 120% 之間——以及 125% 的暴露程度。

What we also noted was that the overall area under the curve was about 11% higher with subcutaneous, and we also noted that there was a 14% increased plaque reduction at the 6-month time point.

我們也注意到，皮下注射的總曲線下面積增加了約 11%，我們也注意到，在 6 個月的時間點，斑塊減少量增加了 14%。

So these are kind of the observations that we have from the data. We have had prior regulatory discussions, and we're now embarking upon additional meetings with the FDA to share the data with them and discuss next steps.

這些是我們從數據中得到的觀察。我們之前已經進行了監管討論，現在我們正在與 FDA 舉行額外的會議，與他們分享數據並討論後續步驟。

So at this point, that's where we are. The plan is as communicated by Eisai to file for a BLA in Q1 -- by Q1 2024. And that's really the update.

現在，這就是我們所處的位置。衛材 (Eisai) 表示，該計劃將在第一季（即 2024 年第一季）提交 BLA。這就是真正的更新。

When -- Eisai has also commented potentially on a maintenance subcutaneous formulation and filing, but that is much later in the 2025 time frame. So that's where we are right now.

衛材也可能對維持皮下製劑和備案發表評論，但那是在 2025 年的時間範圍內。這就是我們現在的處境。

I hope I answered all your questions. Happy to follow up if not.

我希望我回答了你所有的問題。如果沒有的話很樂意跟進。

Thanks, Priya. Let's go to our next question, please.

謝謝，普里亞。請讓我們進入下一個問題。

(Operator Instructions) So while we do, we're going to take our next question from Terence Flynn from Morgan Stanley.

（操作員說明）因此，在我們這樣做的同時，我們將接受摩根士丹利的特倫斯·弗林提出的下一個問題。

I apologize. We next can now go to Robyn Karnauskas from Truist Securities.

我道歉。接下來我們請來 Truist Securities 的 Robyn Karnauskas。

I just want to get a sense of how you think about duration of therapy, given your maintenance data, how should we think about modeling how long people might be in drug at this time with the knowledge that you have for LEQEMBI?

我只是想了解一下您對治療持續時間的看法，考慮到您的維持數據，我們應該如何根據您對 LEQEMBI 的了解來考慮建模人們此時可能服用藥物的時間？

Why don't you start with that, Priya, and then I can finish maybe from a commercial point of view.

Priya，為什麼不從這個開始，然後我也許可以從商業角度來結束。

Yes. Thank you, Robyn. So just stepping back, as we think about the Alzheimer's disease progression, we know that patients actually have plaque reduction. But we have data from several sources now, LEQEMBI, ADUHELM and others that show that while plaque reaccumulates slowly at the rate of about 3% to 4% based on current understanding annually, the biomarkers actually reflecting disease progression continue to accumulate as soon as patients are off drug at least with LEQEMBI and ADUHELM. And this is based on the A-beta 42/40 ratio but also other pathological biomarkers.

是的。謝謝你，羅賓。因此，退一步來說，當我們思考阿茲海默症的進展時，我們知道患者的斑塊實際上有所減少。但我們現在從LEQEMBI、ADUHELM 等多個來源獲得的數據表明，雖然根據目前的了解，每年斑塊以約3% 至4% 的速度緩慢重新積累，但實際上反映疾病進展的生物標誌物一旦患者出現，就會繼續累積。至少使用 LEQEMBI 和 ADUHELM 已停止用藥。這是基於 A-β 42/40 比率以及其他病理生物標記。

We've also shown most recently at CTAD that actually continuing patients on the 24 months, and we showed data on that, which I also shared in my prepared remarks. We saw that while patients who were on placebo, during CLARITY AD study at 18 months and then transitioned on to drug in the open-label extension, they never really caught up with the what we call the early stage early start cohort. However, they maintained their difference with the early start, which we believe is a disease-modifying effect.

最近，我們也在 CTAD 上展示了 24 個月內持續治療的患者，我們也展示了這方面的數據，我也在我準備好的發言中分享了這些數據。我們發現，雖然在 18 個月的 CLARITY AD 研究期間服用安慰劑的患者，然後在開放標籤擴展中過渡到藥物治療，但他們從未真正趕上我們所說的早期早期啟動隊列。然而，他們在早期開始時保持了差異，我們認為這是一種疾病緩解效應。

And then finally, when we superimpose that with the ADME data and the natural history data, we see that the patients who even start at 18 months, actually maintained some level of stabilization on drug.

最後，當我們將 ADME 數據和自然史數據疊加時，我們發現即使在 18 個月時開始的患者實際上也保持了一定程度的藥物穩定性。

So all these areas of evidence point us to the fact that really continuing drug at this point some level is going to be important.

因此，所有這些領域的證據都向我們指出了這樣一個事實：在這一點上，在某種程度上真正繼續用藥將是很重要的。

You're absolutely right that I think we are still evaluating what is the right frequency and for how long, and that is what the maintenance sub study, which is part of the Phase II open-label extension is evaluating, and that's the data that we are gathering. But we believe that drug will need to be continued for a certain period of time, and patients will need to be monitored.

你說得完全正確，我認為我們仍在評估什麼是正確的頻率以及持續多長時間，這就是維護子研究（第二階段開放標籤擴展的一部分）正在評估的數據，這就是我們正在聚會。但我們認為藥物需要持續一段時間，並且需要對患者進行監測。

I mean more broadly, I would say, I've heard many neurologists say, we used to think of Alzheimer's disease as a 4- to 8-year disease, largely beginning with the onset of symptoms.

我想說的是，更廣泛地說，我聽許多神經科醫生說，我們過去認為阿茲海默症是一種 4 到 8 年的疾病，主要是從症狀出現開始的。

With what we know now, a lot of them are saying, we're thinking about this in 25-year terms. We know that patients start to accumulate plaques long before they have symptoms. And as Priya just said, that even after you remove the plaque, there seems to be some benefit in continuing therapy. And as we think about that commercially, first, we have this AHEAD study that has launched, looking at presymptomatic patients. It also raises the importance of blood-based biomarkers, because that's the only way we're going to be able to detect and diagnose or at least triage patients initially at an earlier stage.

就我們現在所知，很多人都說，我們正在 25 年的時間內考慮這個問題。我們知道，患者早在出現症狀之前就開始積聚斑塊。正如 Priya 剛才所說，即使在去除牙菌斑後，繼續治療似乎也會有一些好處。當我們考慮商業方面時，首先，我們已經啟動了這項針對症狀前患者的 AHEAD 研究。它還提高了基於血液的生物標記的重要性，因為這是我們能夠在早期階段檢測和診斷或至少對患者進行分類的唯一方法。

And of course, that's where the subcu formulation also becomes important, because if we are thinking of people staying on drug for longer and I'm certainly not suggesting 25 years. But this could be a much longer period certainly than the 18 months. And therefore, the convenience of the subcu formulation is even more important.

當然，這也是 subcu 配方變得重要的地方，因為如果我們考慮到人們服用藥物的時間更長，我當然不會建議 25 年。但這肯定比 18 個月長得多。因此，subcu配方的便利性就顯得更加重要。

So we are learning every day. I mean, I think we saw that at CTAD with -- we understand increasingly the importance of early treatment. We're seeing the importance of staying or the benefit of potentially staying on treatment, and so that has all kinds of commercial implications and how we do find -- do more studies and develop different formulations. And it's actually quite exciting.

所以我們每天都在學習。我的意思是，我認為我們在 CTAD 上看到了這一點，我們越來越了解早期治療的重要性。我們看到了繼續治療的重要性或可能繼續治療的好處，因此這具有各種商業意義以及我們如何發現 - 進行更多研究並開發不同的配方。這實際上非常令人興奮。

Thanks, Chris. Let's move to the next question, please.

謝謝，克里斯。請讓我們進入下一個問題。

We're next is going to go to Umer Raffat from Evercore.

我們接下來將從 Evercore 前往 Umer Raffat。

I wanted to focus on lucanumab subcu. And Priya, I think you mentioned 2 things. One, that there's a subcu maintenance filing, which is separate, which could be in '25. Could you confirm if the dose is lower if it's a single shot instead of 2?

我想重點關注 lucanumab subcu。 Priya，我想你提到了兩件事。第一，有一個 subcu 維護文件，它是單獨的，可能是在 25 年。您能否確認如果是單次注射而不是兩次注射，劑量是否會較低？

And also, the FDA interactions on subcu that you mentioned, are they a follow-up to previously agreed upon trial design for subcu? Or do you think you need clarity whether plaque reduction alone will suffice for filing?

另外，您提到的 FDA 對 subcu 的互動，是否是先前商定的 subcu 試驗設計的後續行動？或者您認為您需要澄清僅減少牙菌斑是否足以提交申請？

Thanks, Umer. So first of all, I think on the maintenance subcu that is really a much later potential evaluation and filings. So I won't be able to comment further on that specifically with regards to dose, because we first need to evaluate IV maintenance, and that is really the next milestone that's on the docket here.

謝謝，烏默。首先，我認為關於維護子庫，這實際上是一個更晚的潛在評估和歸檔。因此，我無法進一步評論具體關於劑量的問題，因為我們首先需要評估靜脈注射維持，這實際上是這裡待處理的下一個里程碑。

And then going back to your other question of what is the purpose of the FDA regulatory meetings. So maybe just stepping back, Eisai had a number of meetings with FDA prior to the launch of the subcutaneous open-label extension substudy that I spoke about and from CLARITY AD. And so what we do know is that we do need to show bioequivalence on both PK and then we need to show comparability on plaque reduction.

然後回到你的另一個問題，FDA 監管會議的目的是什麼。因此，也許退一步來說，在我談到的 CLARITY AD 皮下開放標籤擴展子研究啟動之前，衛材與 FDA 進行了多次會議。所以我們所知道的是，我們確實需要在 PK 方面表現出生物等效性，然後我們需要在斑塊減少方面表現出可比性。

And based on the 6-month data that we just shared and Eisai spoke to at CTAD, we believe we have achieved that. And so that's the first part. The second part is with that because we have an 11% increase in overall AUC and area under the curve exposure and 14% increased plaque removal, at the 6-month time point, does that result in a different dose? I think that, that is really a matter of discussion, and we would have to discuss that with the FDA, so I can't really comment more on that. But most importantly, I think the goal here was to show bioequivalence, which we believe we have achieved.

根據我們剛剛分享的 6 個月數據以及衛材在 CTAD 上的發言，我們相信我們已經實現了這一目標。這就是第一部分。第二部分是因為在 6 個月的時間點，我們的總體 AUC 和曲線下面積暴露增加了 11%，斑塊去除增加了 14%，這是否會導致劑量不同？我認為，這確實是一個需要討論的問題，我們必須與 FDA 討論這個問題，所以我不能對此發表更多評論。但最重要的是，我認為這裡的目標是展示生物等效性，我們相信我們已經實現了。

And next, we'll go to Michael Yee with Jefferies.

接下來，我們將與 Jefferies 一起採訪 Michael Yee。

I wanted to come back to a topic on the AHEAD 3-45 study. I believe that your partner recently commented there could be an interim analysis based on 400 patients and biomarkers. I noticed that he's been enrolling for a while, but maybe it's just sort of is picking up steam. Can you just maybe talk a little bit about the progress of that study, how you see that study and the status of patients getting in there?

我想回到 AHEAD 3-45 研究的主題。我相信您的合作夥伴最近評論說可能會基於 400 名患者和生物標記進行中期分析。我注意到他已經註冊有一段時間了，但也許只是正在加速。您能否簡單談談研究的進展，您如何看待研究以及參與研究的患者的狀況？

So what I can tell you is that it's a very important part, the AHEAD 3-45 study is a very important part of the overall development plan for LEQEMBI as an anti-amyloid agent.

所以我可以告訴你的是，這是一個非常重要的部分，AHEAD 3-45研究是LEQEMBI作為抗澱粉樣蛋白藥物整體開發計畫的一個非常重要的部分。

And the reason for this is that I think Chris mentioned it as well, just a few minutes ago. that we know that plaque builds up -- amyloid plaque builds up for many years, and then there's sort of a shift where tau tangles start appearing and then you have the appearance of symptoms.

原因是我認為克里斯幾分鐘前也提到了這一點。我們知道斑塊會累積——澱粉樣蛋白斑塊會累積多年，然後會出現某種轉變，tau蛋白纏結開始出現，然後就會出現症狀。

So over the last several years, there's been a lot of work on clinical staging and such, and we know that the anti-amyloid agents that are currently like -- just like LEQEMBI, which is really the only one with traditional approval is targeting mild cognitive impairment, patients with mild cognitive impairment as well as mild dementia. But these patients already have symptoms and potentially a burden of tau.

因此，在過去的幾年裡，在臨床分期等方面做了很多工作，我們知道目前的抗澱粉樣蛋白藥物就像 LEQEMBI 一樣，它實際上是唯一獲得傳統批准的藥物，針對輕度認知障礙，輕度認知障礙以及輕度失智症患者。但這些患者已經出現症狀，可能有 tau 蛋白負擔。

The purpose of AHEAD 3-45 is to look at different levels of amyloid plaque in patients who do not have symptoms, and see whether the addition of an anti-amyloid agent like LEQEMBI can alter the course of disease. So that's really the overarching aim of a study like AHEAD 3-45. It's a very large study. As you can imagine, it's hard to find the patients, but we are very pleased with the progress that the study is making.

AHEAD 3-45 的目的是觀察無症狀患者的澱粉樣蛋白斑塊的不同水平，並觀察添加 LEQEMBI 等抗澱粉樣蛋白藥物是否可以改變病程。這確實是 AHEAD 3-45 這樣的研究的總體目標。這是一項非常大的研究。正如你可以想像的那樣，找到患者很困難，但我們對研究的進展感到非常滿意。

And as Eisai commented very recently, there is the potential to do an interim analysis and think about whether other regulatory pathways are open with interim data. But we haven't really commented beyond that. These remain possibilities, but I think it will depend on how well we do with the recruitment and what the goals of eventual patient access are. Thank you.

正如衛材最近評論的那樣，有可能進行中期分析，並考慮其他監管途徑是否可以利用中期數據。但除此之外我們還沒有真正發表評論。這些仍然是可能性，但我認為這將取決於我們招募的情況以及最終患者訪問的目標是什麼。謝謝。

And next, we'll go to Terence Flynn with Morgan Stanley.

接下來，我們將採訪摩根士丹利的特倫斯弗林。

Great. Just 2-part for me. Just was wondering if you can provide any more detail on the breadth of prescribing for LEQEMBI? I know you gave us the 800 patient number, but if you look at how many centers that's across, that would be helpful.

偉大的。對我來說只有兩個部分。只是想知道您是否可以提供有關 LEQEMBI 處方範圍的更多詳細資訊？我知道您給了我們 800 名患者的號碼，但如果您看看有多少中心，這將會有所幫助。

And then I know you made some comments on some progress on the MAC coverage. Any more details on the time lines there for when we might get broader coverage at the MAC level? I know there's a couple MAC is already covering, but anything there would be helpful.

然後我知道您對 MAC 覆蓋範圍的一些進展發表了一些評論。關於我們何時可以在 MAC 層面獲得更廣泛覆蓋的時間表，還有更多詳細資訊嗎？我知道有幾個 MAC 已經涵蓋了，但任何內容都會有幫助。

Yes. Terence, I don't have any real update on the MAC. There's, I think, with a dozen of them, and they're at various stages. I think by the time that's more -- that most of them have got there, I think there's an assumption that, that takes anywhere from 60 to 90 days to get through. So towards the end of the year.

是的。 Terence，我沒有關於 MAC 的任何實際更新。我想，有十幾個這樣的人，而且他們處於不同的階段。我認為，當他們中的大多數人都到達那裡時，我認為有一個假設，需要 60 到 90 天才能完成。所以到了年底。

On coverage, it's -- one of the most interesting things is really just the diversity of situations that we see. I talked to some physicians and some major medical centers, they've got the protocol. They've got the treatment. They're putting patients through now on a regular basis. But I've been talking to some major medical centers that you might think that they've got this all handled, and they're still thinking about these protocols.

就報道而言，最有趣的事情之一實際上是我們看到的情況的多樣性。我和一些醫生和一些主要的醫療中心交談過，他們有協議。他們已經接受治療了。他們現在正在定期為患者提供服務。但我一直在與一些主要的醫療中心交談，你可能認為他們已經解決了這一切，而且他們仍在考慮這些協議。

And it's protocols are around what's the right profile of the patient to put in this. There is a teamwork approach on this. And so people have to connect on that. For some of the IDNs, they have all of the elements, but they have to connect internally with their MRI centers with the infusion centers.

它的協議是圍繞著患者的正確概況進行的。在這方面有一個團隊合作的方法。因此人們必須就此建立聯繫。對於某些 IDN，它們擁有所有要素，但它們必須在內部將 MRI 中心與輸液中心連接起來。

So it's a little hard to give you a broad brush. I would say every day, we are finding more and more patients, obviously, getting through the course. We are looking upstream at a number of indicators because really revenue is a lagging indicator between even when we start looking at registry results, it's somewhere between 4 to 6 weeks before we actually see those patients going on drug. But some of those time lines are changing constantly.

所以給你一個大致的範圍有點困難。我想說，每天我們都會發現越來越多的患者顯然正在完成課程。我們正在關注上游的一些指標，因為真正的收入是一個滯後指標，即使我們開始查看登記結果，我們也需要 4 到 6 週才能真正看到這些患者服用藥物。但其中一些時間線正在不斷變化。

So it's a pretty moving process here. It's just, every day it changes. And so that's where, at some point, we get enough momentum, we get enough of these barriers cleared. One of the biggest is still the getting an appointment with a neurologist. And that's where I think we're looking at, what can we do with blood-based biomarkers, which are now available, not obviously to replace PET scans or MRIs, but can we use them to triage patients so that those who actually get into a neurology clinic are the ones who are already eligible.

所以這是一個非常感人的過程。只是，每天都在變化。因此，在某個時刻，我們獲得了足夠的動力，我們清除了足夠的障礙。其中最大的問題之一仍然是預約神經科醫生。我認為這就是我們正在考慮的地方，我們可以用現在可用的基於血液的生物標記做什麼，顯然不能取代 PET 掃描或 MRI，但我們可以使用它們對患者進行分類，以便那些真正進入的人神經內科診所是那些已經符合資格的診所。

So there's an awful lot of thinking right on the fly as we learn from this experience. Again, this is really one where the -- there aren't really great analogs. Some people try to suggest the CAR-T approach. And while that is also a product in a process, the volumes, the scale of this is much different, and we're not obviously anywhere near as complex as a CAR-T approach.

因此，當我們從這次經驗中學習時，我們會立即進行大量思考。再說一次，這確實是一個沒有真正偉大的類似物的地方。有些人嘗試提出 CAR-T 方法。雖然這也是一個過程中的產品，但其數量和規模有很大不同，而且我們顯然沒有 CAR-T 方法那麼複雜。

So for us, there's not really any analogs we can do, and so we're learning on the fly as we go along. But like I say, every day brings progress and all of the indicators are in green so far, and it is really just getting enough critical mass now of all the centers who've got these care networks and Care Pathways in place.

所以對我們來說，我們實際上沒有任何類似的東西可以做，所以我們在前進的過程中不斷學習。但就像我說的，每一天都會帶來進步，到目前為止，所有指標都是綠色的，現在所有擁有這些護理網絡和護理途徑的中心實際上剛剛獲得了足夠的臨界質量。

And next, we're going to go to Paul Matteis from Stifel.

接下來，我們將邀請 Stifel 的 Paul Matteis。

Chris, you just mentioned getting an appointment with neurologists. And then earlier in the call, you talked about the registry requirement not being as much of a challenge. I wanted to ask about the other components of the infrastructure here with LEQEMBI, IVs, PET scans and MRIs. How would you rank order these components of the equation as it relates to most and least challenging percenters to navigate? And how do you envision this kind of whole infrastructure network looking by, say, next summer?

克里斯，你剛剛提到與神經科醫生預約。然後在電話會議的早些時候，您談到註冊要求並不是那麼大的挑戰。我想問這裡基礎設施的其他組成部分，包括 LEQEMBI、IV、PET 掃描和 MRI。當方程式的這些組成部分與導航最具挑戰性和最不具有挑戰性的百分比相關時，您將如何排序？您如何看待明年夏天的這種整體基礎設施網路？

Yes. The situation is a little heterogeneous. I mean it's not quite the same situation in every center. But I would say based on what we know today, I do think there is -- there's clearly, at the moment, the need to get an appointment with the neurologist.

是的。情況有點異質。我的意思是每個中心的情況並不完全相同。但我想說，根據我們今天所知道的情況，我確實認為目前顯然需要與神經科醫生預約。

The reality is that there weren't that many patients already in neurology practices. They tend to be in PCP practices. And the neurology practices -- neurologists were already busy. So -- and we have quite a volume of patients now to put through those neurology practices. And a lot of them are realizing -- and then we have to staff up on here. Do I have enough business to justify staffing up and not necessarily with neurologists, but with nurse practitioners, others who can take on some of the parts of the care pathway.

現實情況是，神經病學實踐中的患者並不多。他們常從事 PCP 實務。神經病學實踐－神經科醫生已經很忙了。因此，我們現在有相當多的患者需要接受這些神經病學實踐。他們中的很多人都意識到了——然後我們必須在這裡增加人員。我是否有足夠的業務來證明人員配備的合理性，不一定是神經科醫生，而是執業護士，以及其他可以承擔護理途徑某些部分的人員。

With some of them, it's going through their internal governance process and determining which patients, I think, appropriately at this stage, there's clearly an awful lot of caution around ARIA. My personal belief is that over time, neurologists will become more accustomed to understanding ARIA. Is there a difference between the asymptomatic and the symptomatic, and they'll have a lot more experience, but they're looking at making sure that the patients who go through are trying to get to have the least risk of ARIA.

對於其中一些公司來說，它正在經歷他們的內部治理流程，並確定哪些患者，我認為，在這個階段，ARIA 顯然非常謹慎。我個人相信，隨著時間的推移，神經科醫生將更習慣理解 ARIA。無症狀和有症狀之間有區別嗎？他們會有更多的經驗，但他們正在考慮確保經歷 ARIA 的患者努力將 ARIA 的風險降到最低。

I don't think the infusion center capacity seems to be a big issue for most centers. PET scans, there are enough PET scans as far as we can tell. It's really been around how do I get reimbursement for it? Is it just one? And it was more of the confusion around it. So I think the clarity of that will just take one of the factors of discussion and time out of the process.

我認為輸液中心的容量對於大多數中心來說似乎不是一個大問題。 PET 掃描，據我們所知，有足夠的 PET 掃描。確實存在這樣的問題：我該如何獲得報銷？難道只有一個嗎？更多的是圍繞它的混亂。因此，我認為這一點的明確性只會消除整個過程中討論和時間的因素之一。

And there is just -- at each stage, if you send someone out to the PET scan, the scans got to come back. It's been interpreted by a PET scan reader there, but sometimes a physician will want to have someone in that practice read that. So -- and it's just connecting, sending the patient to all these different points even if you're in an integrated delivery network.

在每個階段，如果你派人去做 PET 掃描，掃描結果就會回來。它已由 PET 掃描閱讀器解讀，但有時醫生會希望讓從事該實踐的人員閱讀該內容。因此，它只是連接，將患者發送到所有這些不同的點，即使您處於整合的交付網路中。

So I don't think it's necessarily any one thing, although I would say if we can do a better job of getting patients triage even before they can get to the neurologist, that could certainly be helpful. But I think it really is -- this is changing the practice paradigm for a lot of clinics, and they're all having to work through it. And these, of course, are super busy people. They've got other needs and so trying to fit in the time to actually manage all this is actually a challenge.

因此，我認為這不一定是一件事，儘管我想說，如果我們能夠更好地在患者去看神經科醫生之前對他們進行分類，那肯定會有所幫助。但我認為確實如此——這正在改變許多診所的實踐範式，他們都必須克服它。當然，這些人都是超級忙碌的人。他們還有其他需求，因此試圖抽出時間來實際管理這一切實際上是一個挑戰。

So I think it's completely natural and expected that this is progressing slowly. But again, you see some who are racing ahead, and that certainly gives me the confidence that others are going to figure this out, too.

所以我認為這是完全自然的，並且預計進展緩慢。但同樣，你會看到一些人正在領先，這無疑讓我相信其他人也會解決這個問題。

We can go to our last question, and that will be from Phil Nadeau from TD Cowen.

我們可以討論最後一個問題，來自 TD Cowen 的 Phil Nadeau。

I want to ask about the SKYCLARYS EMA review. Could you give a bit more of an update on what the status of that review is? Has there been a need for an oral explanation? And generally, what's Biogen's confidence that a positive CHMP opinion will be secured in the first half of 2024?

我想詢問有關 SKYCLARYS EMA 審核的問題。您能否提供有關該審核狀態的更多最新資訊？是否需要口頭解釋？整體而言，百健 (Biogen) 在 2024 年上半年獲得 CHMP 正面意見的信心有多大？

Priya, do you want to take that one?

Priya，你想拿那個嗎？

Sure. Thanks for the question. So overall, just stepping back during diligence, we reviewed regulatory correspondence and we had a certain level of understanding of the topics. And subsequent to closing the deal, we have had more regulatory interactions and nothing has changed our view, as Chris mentioned. We still expect to see an outcome in early 2024, so that remains on track. With regards to whether or not there will be an oral explanation, that is really something we don't comment on because it's under review, and that's part of the review detail. So I hope that helps.

當然。謝謝你的提問。因此，總的來說，在盡職調查期間，我們回顧了監管信件，並對這些主題有了一定程度的了解。正如克里斯所提到的，在交易完成後，我們進行了更多的監管互動，但我們的觀點並沒有改變。我們仍預計在 2024 年初看到結果，因此一切仍按計劃進行。至於是否會有口頭解釋，這確實是我們不評論的事情，因為它正在審查中，這是審查細節的一部分。所以我希望這會有所幫助。

Thanks, Priya, and this will conclude our call. Thanks, everyone, for joining us today. And the IR team will be available later on, of course, for any other follow-up questions.

謝謝 Priya，我們的通話就到此結束。謝謝大家今天加入我們。當然，IR 團隊稍後將解答任何其他後續問題。

Thank you. And ladies and gentlemen, that does conclude today's conference. We appreciate your participation. Have a wonderful day.

謝謝。女士們、先生們，今天的會議到此結束。我們感謝您的參與。祝你有美好的一天。