(BIIB) 2022 Q4 法說會逐字稿

Good morning. My name is Bettina, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen Fourth Quarter and Full Year 2022 Earnings Call and Business Update. (Operator Instructions) Thank you. I would now like to turn the conference over to Mr. Mike Hencke, Head of Investor Relations. Mr. Hencke, you may begin your conference.

早上好。我叫貝蒂娜，今天我將擔任你們的會議接線員。此時，我想歡迎大家參加百健（Biogen）第四季度和 2022 年全年收益電話會議和業務更新。 （操作員說明）謝謝。我現在想將會議轉交給投資者關係主管 Mike Hencke 先生。 Hencke 先生，您可以開始您的會議了。

Thank you. Good morning, and welcome to Biogen's Fourth Quarter and Full Year 2022 Earnings Call. Before we begin, I encourage everyone to go to the Investors section of biogen.com to find 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.

謝謝。早上好，歡迎來到 Biogen 的第四季度和 2022 年全年收益電話會議。在我們開始之前，我鼓勵大家去 biogen.com 的投資者部分找到收益發布和相關財務表格，包括我們的 GAAP 財務指標和我們今天將討論的 GAAP 與非 GAAP 財務指標的調節。

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 discussions related to this call.

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 財務結果的對賬。我們相信，非 GAAP 財務業績更好地代表了我們業務的持續經濟狀況，並反映了我們如何在內部管理業務。我們還在我們的網站上發布了幻燈片，跟進與本次電話會議相關的討論。

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，我們將根據我們的預期做出前瞻性陳述。這些陳述受某些風險和不確定因素的影響，我們的實際結果可能存在重大差異。我鼓勵您查閱我們在 SEC 文件中討論的風險因素以獲取更多詳細信息。

On today's call, I'm joined by our President and Chief Executive Officer, Christopher Viehbacher, Dr. Priya Singhal, Head of Development; and our CFO, Mike McDonnell. (Operator Instructions) I'll now turn the call over to Chris.

在今天的電話會議上，我們的總裁兼首席執行官 Christopher Viehbacher、開發主管 Priya Singhal 博士和我一起出席了會議；以及我們的首席財務官 Mike McDonnell。 （操作員說明）我現在將電話轉給克里斯。

Thank you, Mike. Good morning, everybody, and thanks for joining us. It's a pleasure to welcome you here today. This is my first earnings call since joining Biogen. Now, clearly, Biogen has a strong legacy as one of the pioneers in biotechnology, and there's clearly a strong foundation to build upon. Equally, there's an urgent need to restore growth to the company.

謝謝你，邁克。大家早上好，感謝您加入我們。很高興今天能在這裡歡迎您。這是我加入 Biogen 後的第一次財報電話會議。現在，很明顯，Biogen 作為生物技術的先驅之一擁有強大的遺產，並且顯然有堅實的基礎可以建立。同樣，迫切需要恢復公司的增長。

We have a great opportunity ahead with a potential launch of 2 important near-term launches with Alzheimer's and depression, and we have several pipeline programs. We'll be covering a lot more about how we intend to return to growth. But first, I'd like to turn this over to Mike and invite Mike to provide an overview of the fourth quarter and full year financial results.

我們有一個很好的機會，可能會推出 2 個重要的近期發射阿爾茨海默氏症和抑鬱症，我們有幾個管道項目。我們將詳細介紹我們打算如何恢復增長。但首先，我想把這個交給邁克，並邀請邁克概述第四季度和全年的財務業績。

Thank you, Chris, and good morning, everyone. So I will provide some highlights of the financial performance for the fourth quarter and any financial comparisons that you hear me make will be versus the fourth quarter of 2021.

謝謝克里斯，大家早上好。因此，我將提供第四季度財務業績的一些亮點，你聽到我所做的任何財務比較都將與 2021 年第四季度進行比較。

Our total revenue for the fourth quarter was $2.5 billion, and that's a decrease of 7% at actual currency and 4% at constant currency. Non-GAAP diluted EPS in the fourth quarter was $4.05, and that's an increase of 19% versus the fourth quarter of 2021.

我們第四季度的總收入為 25 億美元，按實際貨幣計算下降 7%，按固定匯率計算下降 4%。第四季度非美國通用會計準則攤薄後每股收益為 4.05 美元，比 2021 年第四季度增長 19%。

MS product revenue was $1.3 billion, and that's a decrease of 17% at actual currency and 14% at constant currency. And this decline was primarily due to the impact of TECFIDERA generics as well as continued declines in the interferons and some pricing pressure. We have continued to see a number of the TECFIDERA generics launch across multiple European countries, and we expect a decision from the European Court of Justice related to our market protection by March 16 of this year.

MS 產品收入為 13 億美元，按實際貨幣計算下降 17%，按固定匯率計算下降 14%。而這種下降主要是由於TECFIDERA仿製藥的影響以及乾擾素的持續下降和一些定價壓力。我們繼續看到許多 TECFIDERA 仿製藥在多個歐洲國家上市，我們預計歐洲法院將在今年 3 月 16 日之前就我們的市場保護做出裁決。

Separately, we do continue to enforce our recently granted European TECFIDERA dosing patent, which expires in 2028. We also continue to enforce our IP for TYSABRI. We have sued Polpharma and Sandoz to enforce those rights that have moved for a preliminary injunction against the launch of Sandoz and Polpharma's biosimilar in the United States.

另外，我們確實繼續執行我們最近授予的歐洲 TECFIDERA 劑量專利，該專利將於 2028 年到期。我們還繼續執行我們的 TYSABRI 知識產權。我們已起訴 Polpharma 和 Sandoz 以行使這些權利，這些權利已針對 Sandoz 和 Polpharma 的生物仿製藥在美國推出的初步禁令提出申請。

Regarding potential supply constraints for VUMERITY, we believe that we have resolved previously reported manufacturing issues at our contract manufacturer. We're currently in the process of securing regulatory approvals for a secondary source of supply, and we do not anticipate a supply shortage in 2023.

關於 VUMERITY 的潛在供應限制，我們相信我們已經解決了我們的合同製造商之前報告的製造問題。我們目前正在為二級供應來源爭取監管批准，我們預計 2023 年不會出現供應短缺。

Moving now to SMA. Global SPINRAZA revenue was $459 million, and that's a 4% increase in actual currency and 10% at constant currency. In the United States, SPINRAZA revenue increased by 5% versus the prior year, and we continue to believe that we may be seeing signs of stabilization.

現在轉到 SMA。 SPINRAZA 的全球收入為 4.59 億美元，按實際貨幣計算增長 4%，按固定匯率計算增長 10%。在美國，SPINRAZA 的收入比上一年增長了 5%，我們仍然相信我們可能會看到穩定的跡象。

Outside of the U.S., revenue increased 4% at actual currency and 12% at constant currency, with continued growth primarily in our Asian markets, and that was partially offset by competition in Europe.

在美國以外地區，收入按實際貨幣計算增長 4%，按固定匯率計算增長 12%，主要在我們的亞洲市場持續增長，但部分被歐洲的競爭所抵消。

Biosimilars revenue was $175 million, and that's a 21% decline in actual currency and 15% at constant currency. And that's due to continued pricing pressure and some net pricing adjustments during the quarter.

生物仿製藥收入為 1.75 億美元，按實際貨幣計算下降 21%，按固定匯率計算下降 15%。這是由於持續的定價壓力和本季度的一些淨定價調整。

Total anti-CD20 revenue of $448 million was up 8% versus the prior year. Revenue from OCREVUS royalties increased 19%, which was partially offset by a revenue decline of 14% related to our profit share on RITUXAN. The RITUXAN decline was due to biosimilar competition.

抗 CD20 總收入為 4.48 億美元，比上年增長 8%。來自 OCREVUS 特許權使用費的收入增長了 19%，這被與我們在 RITUXAN 上的利潤份額相關的收入下降 14% 所部分抵消。 RITUXAN 的下降是由於生物仿製藥的競爭。

Regarding expenses, for the fourth quarter, non-GAAP cost of sales was $571 million, which is 22% of revenue and that includes $36 million of idle capacity charges. Eisai's share of these charges is reflected as part of the collaboration profit sharing line, and that is not part of cost of sales.

關於費用，第四季度，非美國通用會計準則銷售成本為 5.71 億美元，佔收入的 22%，其中包括 3600 萬美元的閒置產能費用。衛材在這些費用中的份額反映在合作利潤分享線的一部分，而不是銷售成本的一部分。

Fourth quarter non-GAAP R&D expense was $602 million, and this compared to $700 million in the fourth quarter of 2021 and the fourth quarter of 2021 included approximately $110 million in payments related to some business development transactions.

第四季度非 GAAP 研發費用為 6.02 億美元，而 2021 年第四季度為 7 億美元，而 2021 年第四季度包括與某些業務發展交易相關的約 1.1 億美元的付款。

Non-GAAP SG&A was $632 million, and this compared to $785 million in the fourth quarter of 2021, and this decrease in SG&A expense was driven primarily by our previously announced cost savings initiatives.

非 GAAP SG&A 為 6.32 億美元，而 2021 年第四季度為 7.85 億美元，SG&A 費用的減少主要是由我們之前宣布的成本節約計劃推動的。

We remain on track to achieve our previously announced $1 billion in cost savings initiatives, and I'll comment on this a bit further when I discuss our guidance for 2023.

我們仍然有望實現我們之前宣布的 10 億美元的成本節約計劃，我將在討論 2023 年的指導方針時進一步評論這一點。

As for our balance sheet, we ended the quarter with $5.6 billion in cash and marketable securities. We had $6.3 billion in debt and roughly $700 million in net debt. And as a reminder, we expect to receive an additional $1.25 billion over the next 15 months from the sale of our equity stake in Samsung Bioepis and that includes approximately $813 million, which is due in April of this year.

至於我們的資產負債表，我們在本季度結束時擁有 56 億美元的現金和有價證券。我們有 63 億美元的債務和大約 7 億美元的淨債務。提醒一下，我們預計在未來 15 個月內通過出售我們在 Samsung Bioepis 的股權獲得額外的 12.5 億美元，其中包括將於今年 4 月到期的約 8.13 億美元。

So overall, we remain in a very strong financial position with significant cash and financial capacity to invest in growing the business over time. Later in the call, I will discuss our guidance assumptions as well as some important accounting considerations for 2023. But for now, I will turn the call back to Chris.

因此，總的來說，我們的財務狀況仍然非常強勁，擁有大量現金和財務能力，可以隨著時間的推移投資於業務增長。在電話會議的稍後部分，我將討論我們的指導假設以及 2023 年的一些重要會計考慮因素。但現在，我會將電話轉回給克里斯。

Thank you, Mike. Biogen has recently celebrated its 45th anniversary, and this is a company that has really been built on multiple sclerosis. It had some hemophilia products until it was spun-off as Bioverativ, some of you may recall that in the past, and we have SPINRAZA. So now we really need to think about how do we transform the business?

謝謝你，邁克。百健（Biogen）最近慶祝了其成立 45 週年，這是一家真正建立在多發性硬化症基礎上的公司。它有一些血友病產品，直到它被剝離為 Bioverativ，你們中的一些人可能還記得過去，我們有 SPINRAZA。所以現在我們真的需要考慮我們如何轉變業務？

I know firsthand from talking to a number of neurologists that our products in MS are still considered to be the top products. But obviously, this is becoming a much more competitive environment. And therefore, we really need to think about how do we grow the business in the future.

通過與許多神經學家的交談，我了解到我們的 MS 產品仍然被認為是頂級產品。但顯然，這正在成為一個競爭更加激烈的環境。因此，我們真的需要考慮未來如何發展業務。

Now we have an amazing opportunity with 2 new products. And as many of you know, I've been in this business a long time, and it's pretty rare that you have this opportunity to launch not 1 but 2 major products and not just any products, but products that are really quite transformative in their respective therapeutic areas, and that's obviously the LEQEMBI and zuranolone.

現在我們有 2 種新產品的絕佳機會。正如你們中的許多人所知，我在這個行業工作了很長時間，你們很少有機會推出 2 種主要產品，而不是 1 種主要產品，而且不僅僅是任何產品，而是真正具有變革性的產品各自的治療領域，這顯然是 LEQEMBI 和 zuranolone。

We also have existing products. We can still grow VUMERITY. We can still grow SPINRAZA. And I think we need to take a fresh approach to those and try to reinvigorate the growth of those 2 brands. As many of you will point out to me, Biogen has a cost base that is probably higher than most of its peers.

我們也有現有的產品。我們仍然可以發展 VUMERITY。我們仍然可以種植 SPINRAZA。而且我認為我們需要對這些採取新的方法並嘗試重振這兩個品牌的增長。正如你們中的許多人會向我指出的那樣，Biogen 的成本基礎可能高於大多數同行。

And we need to think about that much more systematically. And some of that may require a reduction in cost. Some of it is actually a realignment with the new growth alternatives. And then we also need to look at the R&D pipeline. Now we don't get very much credit for what we have in R&D, and Priya is going to talk to you about a number of different products that we think have an awful lot of potential. Equally, the neurology franchise is (inaudible) slowly progressing diseases.

我們需要更系統地考慮這一點。其中一些可能需要降低成本。其中一些實際上是與新的增長選擇的重新調整。然後我們還需要看看研發管道。現在，我們在研發方面的成果並沒有得到太多讚譽，Priya 將與您討論一些我們認為具有巨大潛力的不同產品。同樣，神經病學專營權是（聽不清）緩慢發展的疾病。

That means you're automatically into long-term and costly clinical studies. And in addition, we have some projects in there where our Phase III studies are essentially proof-of-concept studies. And so that makes them also inherently riskier. And I think we need to think about how do we balance the pipeline in R&D going forward.

這意味著您會自動進入長期且昂貴的臨床研究。此外，我們在那裡還有一些項目，我們的 III 期研究本質上是概念驗證研究。因此，這也使它們在本質上也更具風險。我認為我們需要考慮如何平衡未來的研發渠道。

And finally, I think we should always be -- any company should always be open to thinking about external growth opportunities. This hasn't always been a major thrust of the company in the past. But I do think that as we expand into other areas such as immunology, rare diseases, psychiatry, that there may be opportunities to bolster those franchises through external growth.

最後，我認為我們應該始終——任何公司都應該始終對考慮外部增長機會持開放態度。過去，這並不總是公司的主要推動力。但我確實認為，隨著我們擴展到免疫學、罕見疾病、精神病學等其他領域，可能有機會通過外部增長來加強這些特許經營權。

So as you know, LEQEMBI has received accelerated approval in the United States in early January. We have, on the same day, filed for a full or traditional approval. And I have to also give credit to our partner, Eisai because within a very short period of time, not only did they file for traditional approval on the same day as receiving accelerated approval but also within weeks, they have filed in, in Europe, in Japan and initiated a rolling submission in China.

如您所知，LEQEMBI 已於 1 月初在美國獲得加速批准。我們在同一天申請了全面或傳統的批准。我還必須讚揚我們的合作夥伴衛材，因為在很短的時間內，他們不僅在獲得加速批准的同一天申請傳統批准，而且在幾週內，他們在歐洲提交了申請，在日本，在中國發起滾動提交。

And obviously, in the short term, the launch in the U.S. is really going to be constricted until we get reimbursement, and that's expected to occur once we have a traditional approval. When we get to confirmation of filing from the FDA, at that point, we'll know whether we have a priority review or not.

顯然，在短期內，在我們獲得報銷之前，在美國的推出確實會受到限制，而一旦我們獲得傳統批准，預計就會發生這種情況。當我們得到 FDA 的備案確認時，我們就會知道我們是否有優先審查。

Under the terms of the agreement, Eisai is principally responsible and leads all of the discussions with CMS. As many of you probably have heard, Eisai has said that they are hoping to receive a broader reimbursement once they get traditional approval and that could be as early as this summer.

根據協議條款，衛材主要負責並領導與 CMS 的所有討論。正如你們中的許多人可能聽說的那樣，衛材表示他們希望在獲得傳統批准後獲得更廣泛的報銷，最早可能在今年夏天。

But as you know, this is not a round like pill that we're launching here. You need to have a PET scan or a lumbar puncture to confirm diagnosis. We're going to have infusion capacity restrictions. Neurologists have already been busy treating patients with other conditions.

但如您所知，這不是我們在這裡推出的圓形藥丸。您需要進行 PET 掃描或腰椎穿刺以確認診斷。我們將限制輸液能力。神經學家已經忙於治療患有其他疾病的患者。

So there will be a question about do we have enough neurologists to expand the patient population? And so there's an awful lot to be done in the near term. In terms of the -- one of the questions that comes up is -- and that will be the main discussion for CMS.

所以會有一個問題，我們是否有足夠的神經科醫生來擴大患者人數？因此，近期有很多工作要做。就- 出現的問題之一是- 這將是CMS 的主要討論。

To me, the Sum of Boxes, the CDR-Sum of Boxes is not really how we look at patient benefit here. As I talk to physicians treating Alzheimer's patients, most of them are really asking, can I still drive a car? Can I feed myself? Can I dress myself? Can I enjoy life with my family? And how can I not be a burden to others?

對我來說，盒子的總和，盒子的 CDR 總和並不是我們在這裡看待患者利益的真正方式。當我與治療阿爾茨海默氏症患者的醫生交談時，他們中的大多數人真的在問，我還能開車嗎？我可以養活自己嗎？我可以自己穿衣服嗎？我可以和家人一起享受生活嗎？又怎能不成為別人的負擔？

And when you actually look at the activities of daily life, we actually saw a 37% improvement versus placebo. And to me, that's where the real benefit of this product is. Now as we look at Alzheimer's, the other message I think I would really like to drive home today is that this is not just a product launch, there is a today and there is a tomorrow.

當您實際查看日常生活活動時，我們實際上看到與安慰劑相比有 37% 的改善。對我來說，這就是該產品的真正優勢所在。現在，當我們看阿爾茨海默氏症時，我想我今天真的很想開車回家的另一個信息是，這不僅僅是一個產品發布，有今天，也有明天。

And certainly, today, everybody is going to be focused on the initial sales of LEQEMBI and that's going to be a question of overcoming some of the infrastructure challenges that we just talked about. There's going to be an awful lot of education of physicians around safety, around the diagnosis and the infrastructure has to expand to be able to provide the PET scans or the CSF testing. But this is really opening up a whole new field.

當然，今天，每個人都將關注 LEQEMBI 的初始銷售，這將是克服我們剛剛談到的一些基礎設施挑戰的問題。將會有大量關於安全、診斷的醫生教育，基礎設施必須擴展才能提供 PET 掃描或 CSF 測試。但這確實是開闢了一個全新的領域。

This is a whole new vista, both for patients and physicians. I can remember 10 years ago, where we've had a lot of failures of medicines in development to reduce amyloid. People had given up hope that this was going to be effective. Actually, it was Biogen's PRIME study that was initiated about 10 years ago that actually showed that there was still hope for this. And of course, it's really the CLARITY study that has really demonstrated the importance of removal of plaque and the potential to impact the decline in cognition.

這對患者和醫生來說都是一個全新的前景。我記得 10 年前，我們在開發減少澱粉樣蛋白的藥物時遭遇了很多失敗。人們已經放棄了希望這會有效。實際上，大約 10 年前開始的 Biogen 的 PRIME 研究實際上表明這仍然是有希望的。當然，正是 CLARITY 研究真正證明了清除牙菌斑的重要性以及影響認知能力下降的潛力。

And what I think this is going to do is unleash a whole wave of research and development, but there's going to be other things. I mean just even things that we're doing. Obviously, there's amyloid, but there are going to be other modalities such as tau, and Priya will talk about our own potential solution in terms of tau.

我認為這將引發一波研發浪潮，但還會有其他事情發生。我的意思是我們正在做的事情。顯然，有澱粉樣蛋白，但還會有其他形式，例如 tau，Priya 將討論我們自己在 tau 方面的潛在解決方案。

But we're also looking at this -- the trial really focused on this 18 months of treatment. What happens at the end of the 18 months? And there are actually already data that indicate staying on drug has a continued benefit. And so in fact, Eisai will be filing before the end of Q4 of this year, an indication for the treatment on a maintenance basis. But one of the other most interesting things I learned, and I've been obviously trying to get up to speed on Alzheimer's over the last 90 days, but it turns out that plaque burden is at its maximum just before symptoms arise.

但我們也在關注這一點——該試驗真正關注的是這 18 個月的治療。 18 個月結束時會發生什麼？實際上已經有數據表明繼續服藥有持續的好處。因此事實上，衛材將在今年第四季度末之前提交申請，表明該藥物維持治療。但我學到的其他最有趣的事情之一，在過去的 90 天裡，我顯然一直在努力加快阿爾茨海默氏症的速度，但事實證明，斑塊負荷在症狀出現之前達到了最大值。

So imagine the benefit if we could actually go earlier and in fact, there is a study called AHEAD that is looking at a preclinical or presymptomatic patients that could be quite interesting. But to do that, of course, other things like blood-based biomarkers or another biomarkers are going to be important.

因此，想像一下如果我們真的可以更早進行研究會帶來什麼好處，事實上，有一項名為 AHEAD 的研究正在研究可能非常有趣的臨床前或症狀前患者。但要做到這一點，當然，基於血液的生物標誌物或其他生物標誌物等其他東西將很重要。

We're going to have to make this a lot more convenient as a treatment and there's subcutaneous treatment formulations in progress. And so what I think you're going to see is just a flood of information over the next 3 to 5 years, as new modalities and new ways of treating Alzheimer's patients come up.

我們將不得不使它作為一種治療更加方便，並且皮下治療配方正在進行中。因此，隨著治療阿爾茨海默病患者的新模式和新方法的出現，我認為您將在未來 3 到 5 年內看到大量信息。

So here, you see the AHEAD study that was launched in 2020 looking at presymptomatic. One of the physicians who treat Alzheimer has told me, we used to think about Alzheimer's as a 7- to 8-year timeframe, which was really from the onset of symptoms until sadly death. Now they're looking at this on a 25-year frame because we know that plaque builds up over time. And in fact, what we call early-stage Alzheimer's today or with this mild cognitive improvement, it's really not.

因此，在這裡，您可以看到 2020 年啟動的針對症狀前的 AHEAD 研究。一位治療阿爾茨海默氏症的醫生告訴我，我們曾經將阿爾茨海默氏症視為 7 到 8 年的時間範圍，實際上是從症狀出現到不幸死亡。現在，他們正在以 25 年的框架來看待這個問題，因為我們知道斑塊會隨著時間的推移而累積。事實上，我們今天所說的早期阿爾茨海默氏症或這種輕微的認知改善，實際上並非如此。

It's actually already pretty advanced by the time you have MCI. We already talked about the potential for maintenance dosing and different modalities. So this is going to be quite an exciting area as we go along.

當您擁有 MCI 時，它實際上已經相當先進了。我們已經討論了維持劑量和不同方式的潛力。因此，隨著我們的進展，這將是一個非常令人興奮的領域。

Now the other exciting areas in major depressive disorder. And there are 21 million people who suffer from this. And every day, you're reading about the major concerns around mental health and society. In fact, STAT just had an article yesterday about the number of younger people who are suffering from depression and feeling sad and even suicidal.

現在，重度抑鬱症的其他令人興奮的領域。有 2100 萬人因此而受苦。每天，您都會閱讀有關心理健康和社會的主要關注點。事實上，STAT 昨天剛剛發表了一篇文章，介紹了患有抑鬱症、感到悲傷甚至想自殺的年輕人的數量。

And so there is a clear need for new treatments. There are over 400 million prescriptions written every year for MDD and other medical health. But what we see is an awful lot of switching between therapies. There's a lot of concern around side effects. It takes a long time for these new medicine -- these existing medicines to work.

因此，顯然需要新的治療方法。每年有超過 4 億張處方用於 MDD 和其他醫療健康。但我們看到的是療法之間的大量轉換。人們對副作用有很多擔憂。這些新藥——這些現有的藥物——需要很長時間才能發揮作用。

And so my personal view is there's an awful lot of unmet need. I was at GlaxoSmithKline when we had Paxil and we had (inaudible). So I'm pretty familiar with what the existing treatments can and cannot do.

所以我個人的看法是，有很多未滿足的需求。當我們有 Paxil 並且我們有（聽不清）時，我在葛蘭素史克（GlaxoSmithKline）。所以我非常熟悉現有的治療方法能做什麼和不能做什麼。

Postpartum depression, another significant area of unmet need, 1 in 8 mothers, we just had a tragic case, as many of us in the Boston area following, and it just demonstrates that there is a real need for a new approach and new treatment here.

產後抑鬱症，另一個未滿足需求的重要領域，八分之一的母親，我們剛剛遇到了一個悲慘的案例，就像波士頓地區的許多人一樣，它只是表明這裡確實需要一種新的方法和新的治療方法.

And this is not necessarily where a big commercial opportunity is, but there is a major societal need and I think that zuranolone can make a big change here. So we have had a priority review granted, and we have now a PDUFA date in August.

這不一定是一個巨大的商業機會所在，但有一個主要的社會需求，我認為 zuranolone 可以在這裡做出重大改變。因此，我們獲得了優先審評，現在 PDUFA 日期定在 8 月。

As you know, we can't launch immediately because it will have to be a DAA review of the scheduling of the drug before we can launch. So we're looking to launch more towards the end of the year. One of the interesting things is I see this every now and then in the media about the controversial data of zuranolone because 6 out of 7 trials were positive.

如您所知，我們不能立即啟動，因為在我們啟動之前必須對藥物的調度進行 DAA 審查。因此，我們希望在年底前推出更多產品。一件有趣的事情是，我時常在媒體上看到關於祖蘭諾酮有爭議的數據，因為 7 項試驗中有 6 項呈陽性。

Folks, when we were developing Paxil years ago, we had to do 6 Phase III studies to get to that worked. There's an incredible placebo effect here, which is why so many companies actually abandon mental health. So when I saw 6 out of 7, I said, "Well, this is absolutely terrific." And so I think there is quite an exciting opportunity here.

伙計們，當我們幾年前開發 Paxil 時，我們必須進行 6 項 III 期研究才能取得成功。這裡有一種令人難以置信的安慰劑效應，這就是為什麼這麼多公司實際上放棄了心理健康。所以當我看到 7 個中的 6 個時，我說，“嗯，這太棒了。”所以我認為這裡有一個非常令人興奮的機會。

We're not going to go after every type of patient, and we're doing a lot of mid-market research. Today, we're finishing the SHORELINE study and that will inform us about who's the right patient for this. And obviously, the label will inform who we are interested. But there's a lot of unresolved symptoms of depression out there.

我們不會針對所有類型的患者，我們正在做大量的中端市場研究。今天，我們將完成 SHORELINE 研究，這將告訴我們誰是合適的患者。顯然，標籤會告知我們對誰感興趣。但是那裡有很多未解決的抑鬱症症狀。

MDD patients with elevated anxiety, we won't clearly have an anxiety indication, but that is an area of MDD patients that we're going to be focusing on and those who are adherence-challenged.

焦慮升高的 MDD 患者，我們不會有明顯的焦慮跡象，但這是我們將關注的 MDD 患者和那些依從性受到挑戰的患者的一個領域。

Going back to existing drugs. I'll just say, obviously, Biogen had enormous success with SPINRAZA. But when you look at it, there are still a lot of potential patients that have been treated adult patients as well as pediatric patients. And we're going to have a fresh look at how we can improve the coverage of this product.

回到現有的藥物。我只想說，顯然，Biogen 在 SPINRAZA 方面取得了巨大的成功。但是當你看它時，仍然有很多潛在的患者已經接受過成人患者和兒科患者的治療。我們將重新審視如何提高該產品的覆蓋率。

Obviously, it's an intrathecal product, which is not necessarily the most convenient. You may have seen we've just done a collaboration with Alcyone to have a new device that would make this more convened for patients who are not wanting to go through the numerous lumbar punctures.

顯然，它是一種鞘內註射產品，不一定是最方便的。您可能已經看到我們剛剛與 Alcyone 合作開發了一種新設備，該設備可以讓那些不想經歷多次腰椎穿刺的患者更方便地進行手術。

We are looking at costs, that's looking at the profitability of our MS franchise. Can we shift some of these costs to supporting our new product launches. We have a biosimilars business, an important business. This is part of the way that we create the economies for the health care system to forge new businesses, but we are looking at whether we can do more with that business or maybe whether others could [sit] on this business.

我們正在研究成本，也就是研究我們 MS 特許經營權的盈利能力。我們能否將其中一些成本轉移到支持我們的新產品發布上？我們有生物仿製藥業務，這是一項重要的業務。這是我們為醫療保健系統創造經濟以打造新業務的方式的一部分，但我們正在研究我們是否可以對該業務做更多的事情，或者其他人是否可以 [坐在] 該業務上。

We're prioritizing the near-term opportunities and really looking at our cost base on a systematic basis. Priya is going to talk about the risk profile and productivity of the R&D pipeline. As I mentioned earlier, we have appointed Priya as Head of Development, I'd like to take the opportunity to congratulate her on that.

我們正在優先考慮近期機會，並真正系統地審視我們的成本基礎。 Priya 將談論研發管道的風險狀況和生產力。正如我之前提到的，我們已任命 Priya 為開發主管，我想藉此機會向她表示祝賀。

We're also looking for a new Head of Research. While we have a lot going on, we still continue to evaluate external growth opportunities. And so I think with that, Priya, why don't we talk about R&D?

我們也在尋找新的研究主管。雖然我們有很多事情要做，但我們仍在繼續評估外部增長機會。所以我認為，Priya，我們為什麼不談談研發呢？

Thank you, Chris. We are advancing LEQEMBI with Eisai as a foothold in Alzheimer's disease, as you heard from Chris, and zuranolone with Sage, both as key late-stage assets, but also as growth drivers.

謝謝你，克里斯。我們正在與衛材一起推進 LEQEMBI 作為阿爾茨海默病的立足點，正如你從 Chris 那裡聽說的那樣，以及與 Sage 一起推進 zuranolone，這兩者都是關鍵的後期資產，也是增長動力。

With Sage, we also announced the FDA acceptance of zuranolone in MDD and PPD as priority review. The PDUFA date is August 5. The priority review is granted by FDA to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment diagnosis or prevention of serious conditions. Beyond these developments, we're also making progress across R&D reprioritization, and today, I will share a few highlights from some of our pipeline programs in Alzheimer's disease, lupus and ALS.

對於 Sage，我們還宣布 FDA 接受 MDD 和 PPD 中的紮蘭諾酮作為優先審查。 PDUFA 日期是 8 月 5 日。FDA 將優先審評授予那些如果獲得批准，將顯著改善治療診斷或預防嚴重疾病的有效性或安全性的藥物申請。除了這些發展之外，我們還在重新確定研發優先級方面取得了進展，今天，我將分享我們在阿爾茨海默病、狼瘡和肌萎縮側索硬化方面的一些管道項目中的一些亮點。

We are advancing a broader Alzheimer's disease pipeline, as you heard from Chris, and we have initiated the Phase II CELIA study of BIIB080 in early Alzheimer's disease. Prior clinical results, including those from our own Phase II gantenerumab suggests that targeting extracellular tau alone is insufficient to affect intracellular tau tangle.

正如您從 Chris 那裡聽說的那樣，我們正在推進更廣泛的阿爾茨海默氏病管道，我們已經啟動了 BIIB080 在早期阿爾茨海默氏病中的 II 期 CELIA 研究。先前的臨床結果，包括我們自己的 II 期 gantenerumab 的結果表明，僅靶向細胞外 tau 不足以影響細胞內 tau 纏結。

BIIB080 is targeting tau mRNA to reduce all forms of the tau protein, post translation. In preclinical studies, we've seen that ASO knockdown of the tau in the transgenic mouse model of neurodegenerative tauopathy, reversed tau pathology, prevented hippocampal volume loss and neuronal death.

BIIB080 靶向 tau mRNA 以減少翻譯後所有形式的 tau 蛋白。在臨床前研究中，我們已經看到在神經退行性 tau 病變的轉基因小鼠模型中，ASO 敲低 tau 蛋白，逆轉 tau 蛋白病理學，防止海馬體積減少和神經元死亡。

This year illustrates the Phase Ib study results of BIIB080 in mild AD. BIIB080 was generally well tolerated, and we observed a time and dose-dependent reduction in CSF total and p-tau. Total tau continued to decline 16 weeks following the last dose with a 50% reduction from baseline.

今年說明了 BIIB080 在輕度 AD 中的 Ib 期研究結果。 BIIB080 總體耐受性良好，我們觀察到 CSF 總量和 p-tau 的時間和劑量依賴性降低。在最後一次給藥後 16 週，總 tau 蛋白繼續下降，比基線下降了 50%。

We were encouraged by this early data, and we look forward to sharing data details from this Ib study at ADPD next month.

我們對這一早期數據感到鼓舞，我們期待著在下個月的 ADPD 上分享這項 Ib 研究的數據細節。

As I mentioned, we have initiated our Phase II CELIA study in 2022. It includes several dosing paradigms, 3 doses and every 12 or 24 weeks dosing. And assessments will evaluate multiple aspects of Alzheimer's disease, cognition, function and biomarkers. We believe that CELIA has the potential to generate important learnings regarding the role of tau in Alzheimer's disease.

正如我提到的，我們已經在 2022 年啟動了我們的 II 期 CELIA 研究。它包括幾個給藥範例，3 劑和每 12 或 24 週給藥一次。評估將評估阿爾茨海默病、認知、功能和生物標誌物的多個方面。我們相信 CELIA 有可能產生關於 tau 在阿爾茨海默病中的作用的重要知識。

Moving on. Biogen has leveraged a very strong scientific expertise in immunology, and this is how the MS franchise was born. I'd like to discuss our 2 Phase III lupus programs next.

繼續。百健（Biogen）在免疫學方面利用了非常強大的科學專業知識，這就是 MS 特許經營權的誕生方式。接下來我想討論我們的 2 個 III 期狼瘡項目。

First is dapirolizumab pegol, which we have in collaboration with UCB currently in Phase III. We also have litifilimab or BIIB059, our wholly owned anti-BDCA2 monoclonal antibody. Both are potential first-in-class molecules in SLE. SLE is an autoimmune disease that can affect multiple organs and can lead to severe organ damage and morbidity, especially amongst the non-Caucasian patients.

首先是 dapirolizumab pegol，我們與 UCB 合作，目前處於 III 期。我們還有 litifilimab 或 BIIB059，這是我們全資擁有的抗 BDCA2 單克隆抗體。兩者都是 SLE 中潛在的 first-in-class 分子。 SLE 是一種自身免疫性疾病，可影響多個器官並可導致嚴重的器官損傷和發病，尤其是在非白種人患者中。

Litifilimab also has the potential to be a first-in-class treatment for CLE. CLE or cutaneous lupus erythematosus is a skin-based autoimmune disease and can exist in the absence of systemic manifestations.

Litifilimab 也有可能成為 CLE 的一流治療藥物。 CLE 或皮膚紅斑狼瘡是一種基於皮膚的自身免疫性疾病，可以在沒有全身表現的情況下存在。

Chronic CLE is associated with severe skin damage and impaired quality of life. No new treatment approved specifically for CLE in almost 70 years.

慢性 CLE 與嚴重的皮膚損傷和生活質量受損有關。近 70 年來，沒有專門針對 CLE 批准的新療法。

The CLE part of the Phase II LILAC study met its primary endpoint, and the results were published last summer in the New England Journal of Medicine. Based upon these encouraging results, we initiated the Phase II/III AMETHYST study of litifilimab in CLE. Lupus disproportionately impacts underrepresented populations, and we have set enrollment targets in litifilimab studies to reflect this high prevalence in African-American and Hispanic or Latino community.

II 期 LILAC 研究的 CLE 部分達到了主要終點，結果於去年夏天發表在新英格蘭醫學雜誌上。基於這些令人鼓舞的結果，我們啟動了 litifilimab 在 CLE 中的 II/III 期 AMETHYST 研究。狼瘡對代表性不足的人群的影響尤為嚴重，我們在 litifilimab 研究中設定了招募目標，以反映這種在非裔美國人和西班牙裔或拉丁裔社區中的高患病率。

Next, I will discuss ALS. ALS is a devastating progressive neurodegenerative disease. SOD1-ALS is an ultra-rare genetic form that affects approximately 330 individuals in the U.S. While the VALOR Phase III study of tofersen in SOD1-ALS did not hit the primary endpoint, we have published our 12-month data from both VALOR and its open-label extension in the New England Journal of Medicine last year.

接下來，我將討論 ALS。 ALS 是一種破壞性的進行性神經退行性疾病。 SOD1-ALS 是一種極其罕見的遺傳形式，在美國影響了大約 330 人。雖然在 SOD1-ALS 中對 tofersen 進行的 VALOR III 期研究沒有達到主要終點，但我們已經發布了 VALOR 及其 12 個月的數據去年新英格蘭醫學雜誌的開放標籤擴展。

In these results, we observed a sustained reduction in neurofilament, which is a marker of axonal injury and neurodegeneration in individuals who initiated to [person] earlier. We also observed a slower decline in measures of clinical and respiratory function as well as strength and quality of life.

在這些結果中，我們觀察到神經絲的持續減少，這是較早開始[人]的個體的軸突損傷和神經變性的標誌。我們還觀察到臨床和呼吸功能指標以及體力和生活質量的下降速度較慢。

With the PDUFA action date of April 25, 2023, Biogen has the potential to deliver (inaudible) targeted therapy to people suffering from SOD1-ALS. FDA recently announced the March 22, 2023, date for the advisory committee meeting for tofersen. EMA has accepted the marketing authorization application for tofersen for review in the European Union.

隨著 PDUFA 行動日期為 2023 年 4 月 25 日，Biogen 有可能為患有 SOD1-ALS 的人提供（聽不清）靶向治療。 FDA 最近宣布了 tofersen 諮詢委員會會議的日期為 2023 年 3 月 22 日。 EMA已受理tofersen在歐盟的上市許可申請審查。

Moving on. At a higher level, as Chris mentioned, our goal is to rebalance the R&D pipeline. In this context, we have developed a framework to guide our decision-making and the focus is on the pre-proof-of-concept programs. For example, we are investing to win in programs where we have a high degree of biological confidence, such as BIIB080, while we continue to apply a systemic, systematic data-driven approach in this program to learn and derisk.

繼續。在更高的層面上，正如克里斯提到的，我們的目標是重新平衡研發渠道。在這種情況下，我們制定了一個框架來指導我們的決策，重點是預概念驗證程序。例如，我們在BIIB080等我們有高度生物學信心的項目上投資取勝，同時我們在這個項目中繼續應用系統的、系統的數據驅動的方法來學習和去風險。

We may also choose to discontinue development for some programs based on their regulatory development or commercialization challenges. Examples of recently discontinuous programs include vixotrigine in neuropathic pain and orelabrutinib in MS.

我們也可能會根據某些項目的監管發展或商業化挑戰選擇停止開發。最近中斷項目的例子包括治療神經性疼痛的vixotrigine 和治療MS 的orelabrutinib。

In parallel, we have several focus areas to help increase the productivity of our pipeline and decrease the risk. First is to derisk and improve probability of success in the pre-proof-of-concept portfolio. Second is to enhance the roll-off and capabilities for translational science and importantly, our overall focus on value generation versus achievement of operational milestones alone.

與此同時，我們有幾個重點領域來幫助提高管道的生產率並降低風險。首先是降低風險並提高概念驗證前投資組合的成功概率。其次是加強轉化科學的發展和能力，重要的是，我們的整體重點是價值創造，而不是僅僅實現運營里程碑。

In conclusion, with key assets in Alzheimer's disease, depression and lupus, we believe the Biogen pipeline has potential to deliver significant growth over the medium and long term. I will now pass the call over back to Mike.

總之，憑藉在阿爾茨海默病、抑鬱症和狼瘡方面的關鍵資產，我們相信百健（Biogen）管道有潛力在中長期實現顯著增長。我現在將把電話轉回給邁克。

So thank you, Priya. I will now go through our 2023 guidance ranges and talk about some of the key assumptions and then we'll open it up for questions. We expect a full year 2023 revenue decline in the mid-single-digit percentage range as compared to 2022 reported results and full year 2023 non-GAAP diluted earnings per share of between $15 and $16.

所以謝謝你，普里亞。我現在將通過我們的 2023 年指導範圍並討論一些關鍵假設，然後我們將公開提問。與 2022 年報告的結果相比，我們預計 2023 年全年收入將下降中個位數百分比範圍，2023 年全年非 GAAP 攤薄每股收益在 15 美元至 16 美元之間。

There are several dynamics that we expect in 2023 that I'd like to highlight. First, our guidance assumes a favorable decision by the Court of Justice of the European Union relating to regulatory data protection for TECFIDERA. And that's currently expected to be on March 16, as I mentioned earlier of this year, although we obviously cannot predict the outcome of that.

我想強調一下我們預計 2023 年的幾個動態。首先，我們的指南假設歐盟法院就 TECFIDERA 的監管數據保護做出了有利的決定。正如我今年早些時候提到的那樣，目前預計將在 3 月 16 日舉行，儘管我們顯然無法預測結果。

This guidance also assumes modest in-market revenue for LEQEMBI in 2023, with commercial expenses -- commercialization expenses exceeding revenue, and Biogen will record its share of net commercial profits and losses for LEQEMBI in the U.S. as a component of total revenue, and we do expect this to be a headwind to our revenue in 2023.

本指南還假設 LEQEMBI 在 2023 年的市場收入適度，商業費用——商業化費用超過收入，百健（Biogen）將記錄其在美國 LEQEMBI 的淨商業利潤和損失的份額作為總收入的一部分，我們預計這將成為我們 2023 年收入的不利因素。

Just as a reminder, in 2022, we amended our collaboration agreement with Eisai for ADUHELM. And as a result, we will have sole decision-making and commercialization rights, along with a substantial majority of the economics beginning in 2023. Eisai will receive a royalty and will no longer share in expenses related to ADUHELM, and this does result in 2 important considerations for 2023.

提醒一下，在 2022 年，我們修改了與衛材的 ADUHELM 合作協議。因此，從 2023 年開始，我們將擁有唯一的決策權和商業化權，以及絕大部分經濟收益。Eisai 將獲得特許權使用費，將不再分擔與 ADUHELM 相關的費用，這確實導致 2 2023 年的重要考慮因素。

First, we expect to incur approximately $150 million to $200 million of excess capacity charges in 2023, and all of that will be borne by Biogen. In 2022, we incurred $119 million of idle capacity. And of that amount, $55 million was reimbursed by Eisai.

首先，我們預計 2023 年將產生大約 1.5 億至 2 億美元的產能過剩費用，所有這些都將由百健（Biogen）公司承擔。 2022 年，我們產生了 1.19 億美元的閒置產能。其中，衛材報銷了 5500 萬美元。

Our cost of sales as a percentage of revenue is expected to be higher in 2023 than the 22.4% that we saw in 2022, and that's as a result of product mix as well as the dynamic that I just described. We expect this pressure on cost of goods sold to be particularly pronounced earlier in the year.

我們的銷售成本佔收入的百分比預計在 2023 年將高於我們在 2022 年看到的 22.4%，這是產品組合以及我剛才描述的動態的結果。我們預計今年早些時候銷售商品成本的這種壓力會特別明顯。

The second result of the amended agreement with Eisai is that we will no longer be sharing ADUHELM R&D costs, and this is expected to create an increase of approximately $100 million in R&D expense in 2023 as compared to 2022.

與衛材修訂後的協議的第二個結果是，我們將不再分擔 ADUHELM 研發費用，預計這將使 2023 年的研發費用比 2022 年增加約 1 億美元。

Full year operating expenses, which are comprised of both SG&A and R&D expense will reflect our previously disclosed $1 billion of cost reduction measures, and we expect that approximately $300 million of these cost savings will be reinvested to support the launch of zuranolone and other new products.

包括 SG&A 和研發費用在內的全年運營費用將反映我們之前披露的 10 億美元的成本削減措施，我們預計這些節省的成本中約有 3 億美元將用於再投資以支持 zuranolone 和其他新產品的推出.

So we expect that this will result in $700 million of net operating expense savings relative to full year 2021 operating expenses, which were approximately $5.2 billion. We are continuing to monitor potential supply constraints for IMRALDI, and our guidance does not assume any stock outs, but this does remain a risk. There are also some key seasonality dynamics that we'd like to note.

因此，我們預計，相對於 2021 年全年的運營費用約為 52 億美元，這將節省 7 億美元的淨運營費用。我們正在繼續監測 IMRALDI 的潛在供應限制，我們的指導不假設任何缺貨，但這確實存在風險。我們還想注意一些關鍵的季節性動態。

As a reminder, Q1 tends to be seasonally weaker, a weaker quarter as compared to Q4 for our MS business in the U.S., and that's due to channel dynamics and the higher discounts and allowances. SPINRAZA benefited in Q4 of 2022 in part due to the timing of some shipments.

提醒一下，與我們在美國的 MS 業務的第四季度相比，第一季度往往季節性較弱，這是一個較弱的季度，這是由於渠道動態以及更高的折扣和津貼。 SPINRAZA 在 2022 年第四季度受益，部分原因是一些發貨的時間安排。

And additionally, as a reminder, the royalty rate for OCREVUS resets at the beginning of each year in this rate increases as sales levels increased throughout the year. We also expect that our operating expenses will be higher earlier in the year given that some of our cost savings initiatives will take time to materialize over the course of 2023.

此外，作為提醒，OCREVUS 的特許權使用費率在每年年初重置，隨著全年銷售水平的增加，該比率會增加。鑑於我們的一些成本節約舉措需要時間在 2023 年實現，我們還預計今年早些時候的運營費用會更高。

And of course, as always, we assume that foreign exchange rates as of December 31, 2022, will remain in effect for the year, net of our hedging activities. And I would refer you to our press release for other important guidance assumptions.

當然，一如既往，我們假設截至 2022 年 12 月 31 日的外匯匯率在扣除我們的對沖活動後將在本年度保持有效。我建議您參閱我們的新聞稿，了解其他重要的指導假設。

Before concluding, I want to highlight a few of the key accounting considerations for LEQEMBI and zuranolone. And now that LEQEMBI has received accelerated approval in the United States, Biogen's 50% share of net commercial profits and losses, which includes in-market revenue less cost of goods, royalties and SG&A will be reflected as a component of total revenue. As I mentioned, we expect this to be negative in 2023 as we expect that commercial expenses will exceed revenue.

在結束之前，我想強調 LEQEMBI 和 zuranolone 的一些關鍵會計考慮因素。現在 LEQEMBI 已在美國獲得加速批准，百健（Biogen）50%的淨商業損益（包括市場內收入減去商品成本、特許權使用費和 SG&A ）將反映為總收入的一個組成部分。正如我所提到的，我們預計 2023 年這將是負數，因為我們預計商業支出將超過收入。

Outside the U.S., our 50% share of commercial expenses will continue to be recorded within SG&A expense until LEQEMBI is approved on a region-by-region basis. Separately, Biogen's 50% share of global LEQEMBI R&D expenditures will continue to be reflected within R&D expense, and this is both before and after approval.

在美國以外，我們 50% 的商業費用份額將繼續記錄在 SG&A 費用中，直到 LEQEMBI 在逐個區域的基礎上獲得批准。另外，Biogen 在全球 LEQEMBI 研發支出中所佔份額的 50% 將繼續反映在研發費用中，這在批准之前和之後都是如此。

And finally, on LEQEMBI, Biogen is manufacturing LEQEMBI drug substance in our Solothurn, Switzerland facility, we capitalized inventory until it is sold to Eisai at which point we will recognize contract manufacturing revenue and contract manufacturing cost of goods sold, and that will be at a minimal gross margin.

最後，在 LEQEMBI 上，百健（Biogen）正在我們位於瑞士索洛圖恩的工廠生產 LEQEMBI 原料藥，我們將庫存資本化，直到將其出售給衛材，屆時我們將確認合同製造收入和所售商品的合同製造成本，這將在最低的毛利率。

Zuranolone is also a 50-50 profit share in the U.S. with our partner Sage Therapeutics. Prior to regulatory approval, we will record our share of R&D and SG&A expense in their respective line items net of reimbursement to or from Sage.

Zuranolone 與我們的合作夥伴 Sage Therapeutics 在美國也有 50-50 的利潤分成。在監管部門批准之前，我們將在扣除 Sage 的報銷後，在各自的項目中記錄我們在研發和 SG&A 費用中的份額。

After U.S. approval, Biogen will record 100% of zuranolone product revenue, cost of goods and SG&A., and then we will share Sage's 50% of profits or losses as a component of Biogen's collaboration profit-sharing line. So in closing, our #1 goal is to return Biogen to sustainable growth.

美國批准後，Biogen 將記錄 100% 的 zuranolone 產品收入、商品成本和 SG&A。然後我們將分享 Sage 的 50% 的利潤或損失，作為 Biogen 合作利潤分享線的組成部分。因此，最後，我們的第一目標是讓百健（Biogen）恢復可持續增長。

We believe that the potential launches of LEQEMBI and zuranolone, along with the rest of our pipeline and our strong balance sheet, provide us with the necessary elements to achieve this goal. And we are also working very hard to improve our operating efficiency and remain committed to creating long-term value for our shareholders.

我們相信 LEQEMBI 和 zuranolone 的潛在上市，以及我們的其他管道和我們強大的資產負債表，為我們提供了實現這一目標的必要要素。我們也在努力提高我們的運營效率，並繼續致力於為我們的股東創造長期價值。

And with that, we'll open up the call for questions.

有了這個，我們將打開問題電話。

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

（操作員說明）您的第一個問題來自高盛的 Salveen Richter。

Maybe a question of whether you can lay out potential timelines for the NCD reconsideration for LEQEMBI? Historical precedent suggests this could take about 9 months. But when is the soonest this process could start? Could it start pre-approval? And when will we know when the process has been initiated?

也許是一個問題，你是否可以為 LEQEMBI 的 NCD 重新考慮制定潛在的時間表？歷史先例表明這可能需要大約 9 個月的時間。但是這個過程最快什麼時候開始？能否啟動預批？我們什麼時候才能知道流程何時啟動？

Yes, thanks for the question. Look, I'm not so sure, first of all, that precedent is going to really matter here. I think this is an unusual set of circumstances. And -- so there are negotiations and discussions ongoing between Eisai and CMS today. CMS could decide whatever, but the feeling is, is that they're going to wait until there is a traditional approval and then we'll see.

是的，謝謝你的提問。看，我不太確定，首先，這個先例在這裡真的很重要。我認為這是一組不尋常的情況。而且 - 所以今天衛材和 CMS 之間正在進行談判和討論。 CMS 可以決定任何事情，但感覺是，他們將等到傳統批准，然後我們再看。

Will there be a registry, won't there be a registry, we just don't know at this stage. What I would say is that I think you're seeing a much different tone in the broader community than we had with ADUHELM. You've seen the American Association of Neurologists write to CMS to support reimbursement. You've seen members of Congress, I can tell you that the neurology community look at -- broadly look at the CLARITY data as being very compelling in terms of the impact.

會不會有註冊表，會不會有註冊表，我們現階段還不知道。我想說的是，我認為您在更廣泛的社區中看到的基調與我們在 ADUHELM 上看到的基調大不相同。您已經看到美國神經病學家協會寫信給 CMS 以支持報銷。你見過國會議員，我可以告訴你，神經病學界——廣泛地認為 CLARITY 數據在影響方面非常引人注目。

Obviously, CMS makes its own decisions. But I think there's a growing consensus that this is a medicine that is very much needed by a broad population, and Eisai has guided to their hope that there would be this broader reimbursement once they have traditional approval.

顯然，CMS 自己做決定。但我認為，越來越多的人認為這是一種廣泛人群非常需要的藥物，而衛材已經引導他們希望一旦獲得傳統批准，就會有更廣泛的報銷。

Our next question comes from the line of Mohit Bansal of Wells Fargo.

我們的下一個問題來自富國銀行的 Mohit Bansal。

Maybe a question on expense cuts. So I know earlier this year, you talked about expense cuts. And I mean, if you do the math, it's very clear that for the product portfolio, the expense base is very high. Can you talk about -- I mean have you thought about your target operating margin profile long term? And how much more cuts can you do? And any timelines when we could hear about this? Because you also talked about almost $200 million of spend here. You said that you will probably prioritize and figure out whether you want to keep spending that money or not. So can you talk a little bit about the timelines of that now that you are in the business review more?

也許是關於削減開支的問題。所以我知道今年早些時候，你談到了削減開支。我的意思是，如果你算一下，很明顯，對於產品組合來說，費用基數非常高。你能談談——我的意思是你有沒有考慮過你的長期目標營業利潤率？你還能削減多少？我們什麼時候可以聽到這個消息？因為你還談到了近 2 億美元的支出。你說你可能會優先考慮並弄清楚你是否想繼續花那筆錢。那麼，既然您更多地參與業務審查，您能談談時間表嗎？

In OpEx, you've got 2 big buckets, right? You've got R&D and you've got SG&A. In R&D, we are looking at this whole prioritization exercise. And that means if you want to save money to a degree you have to -- you may have to cut some programs. And that's not something that you want to do quickly. You need to go and look at each program thoroughly, determine probabilities of success, cost to complete, a whole bunch of other things.

在 OpEx 中，您有 2 個大桶，對嗎？你有研發，你有 SG&A。在研發中，我們正在研究整個優先級排序工作。這意味著如果你想把錢省到一定程度——你可能不得不削減一些項目。這不是您想快速完成的事情。您需要仔細查看每個程序，確定成功的概率、完成成本以及一大堆其他事情。

There is an infrastructure element to R&D that we will be looking at as a matter of priority. And then you have SG&A. And within the sales and marketing, obviously, most of that spend is really going to the MS franchise. Now the MS franchise still supports most of our revenue in the business. And so one has to be careful about how much we want to reduce that spend by, but clearly, that's a declining revenue base.

我們將優先考慮研發的基礎設施要素。然後你有 SG&A。顯然，在銷售和營銷方面，大部分支出都用於 MS 特許經營權。現在 MS 特許經營權仍然支撐著我們業務的大部分收入。因此，人們必須謹慎考慮我們希望將支出減少多少，但顯然，這是一個不斷下降的收入基礎。

And so I think what you're really going to see is a shift from some of those resources to supporting the launch. Now there's hundreds of millions of dollars going between Eisai, Sage and Biogen behind the prelaunch activities this year for LEQEMBI and zuranolone. And those are obviously strategic products for all of the companies, and we really need to support the launches.

因此，我認為您真正要看到的是從其中一些資源轉向支持發布。現在，今年 LEQEMBI 和 zuranolone 的上市前活動背後，衛材、Sage 和百健（Biogen）之間投入了數億美元。這些顯然是所有公司的戰略產品，我們確實需要支持這些產品的發布。

But we have to be -- find the right balance and not seeing a decline in MS sales beyond what we already see. And then there is G&A, and we will be taking a close look at that this year. So you're going to see some reductions in cost, but there's also going to be some new investments. And so it's a little hard to say at this point where we're going to end up on margins.

但我們必須——找到合適的平衡點，不要看到 MS 銷量的下降超出我們已經看到的範圍。然後是 G&A，今年我們將仔細研究。所以你會看到成本有所降低，但也會有一些新的投資。因此，在這一點上很難說我們最終會獲得利潤。

But if you strip out the royalty and collaboration income and do the OpEx to sales ratios, we're clearly higher than most of our peer companies. And considering that we have a fairly mature product profile of high volume -- of high-value, low-volume products, we should be more profitable.

但如果你剔除特許權使用費和合作收入併計算運營支出與銷售額的比率，我們顯然高於大多數同行公司。考慮到我們擁有相當成熟的高容量產品配置文件——高價值、低容量的產品，我們應該更有利可圖。

But the company has already taken $1 billion out. So that means more cost savings have to be done thoughtfully. So we'll be giving you updates throughout the year on that. But we are conscious that the cost base needs to be more productive than it is.

但該公司已經拿出了 10 億美元。因此，這意味著必須深思熟慮地節省更多成本。因此，我們將全年為您提供最新信息。但我們意識到成本基礎需要比現在更俱生產力。

On ADUHELM, ADUHELM will see -- we will be looking at the EMBARK data, which is long term, that will give some information about not just for ADUHELM, but also how we think about the longer-term treatment of amyloid-reducing antibodies. There, we also need to see exactly what the landscape is. What I can tell you is, there is no commercial effort behind ADUHELM.

在 ADUHELM 上，ADUHELM 將看到——我們將查看長期的 EMBARK 數據，這些數據不僅會提供有關 ADUHELM 的一些信息，還會提供我們如何考慮澱粉樣蛋白減少抗體的長期治療的信息。在那裡，我們還需要確切地看到風景是什麼。我可以告訴你的是，ADUHELM 背後沒有任何商業努力。

Our focus is on LEQEMBI. We believe that is the product that is most appropriate for patients. We do have a commitment to the FDA to do this confirmatory study. So we have to think through that carefully. But I just want to be clear that from a strategic point of view, LEQEMBI is our absolute priority, and ADUHELM is not being actively commercialized anywhere.

我們的重點是 LEQEMBI。我們相信這是最適合患者的產品。我們確實向 FDA 承諾進行這項驗證性研究。所以我們必須仔細考慮。但我只想明確一點，從戰略角度來看，LEQEMBI 是我們的絕對優先事項，ADUHELM 並未在任何地方積極商業化。

Our next question comes from Colin Bristow of UBS.

我們的下一個問題來自瑞銀的 Colin Bristow。

One for Chris. In terms of your ongoing review of the business and the pipeline, how should we be thinking about timelines just in terms of the potential for strategic actions with ADUHELM? And then just more broadly in terms of business development, when you're sort of clearly identified the targets that would be potentially willing to move forward?

一個給克里斯。就您對業務和管道的持續審查而言，我們應該如何僅根據與 ADUHELM 採取戰略行動的可能性來考慮時間表？然後更廣泛地在業務發展方面，當你清楚地確定了可能願意向前推進的目標時？

And then just within this question, could you just characterize your ongoing interest in biosimilars?

然後就在這個問題中，您能否描述一下您對生物仿製藥的持續興趣？

So on R&D, again, you have a number of projects that have been ongoing for a number of years. We have a number of products actually in Phase III that are actually proof-of-concept studies. There are at least -- not even including ADUHELM, we have 3 products in development where we did not have safety or efficacy data out of a positive Phase II.

因此，在研發方面，您有許多項目已經進行了多年。實際上，我們有許多處於 III 期的產品實際上是概念驗證研究。至少——甚至不包括 ADUHELM，我們有 3 種產品正在開發中，我們沒有來自積極的 II 期的安全性或有效性數據。

So I think we need to think carefully about each of those programs. It does take some time, and there is always a question of, well, how much do we have to spend to the next milestone? And is that really worth it? Can we think about different ways of doing the study?

所以我認為我們需要仔細考慮每一個項目。這確實需要一些時間，而且總是有一個問題，好吧，我們必須花多少錢才能達到下一個里程碑？這真的值得嗎？我們可以考慮不同的研究方法嗎？

Can we derisk these? So that will probably take us through to the summer before I think we can really make too many decisions on that front. Biosimilars, it's an extremely strong team, and they've built a successful business, but I look at Biogen as a company with innovative medicines.

我們可以嘲笑這些嗎？所以這可能會帶我們度過夏天，然後我認為我們真的可以在這方面做出太多決定。 Biosimilars，這是一個非常強大的團隊，他們已經建立了成功的業務，但我將 Biogen 視為一家擁有創新藥物的公司。

We're not a huge company by any means, and there needs to be a focus. So we are looking at what's the right business model for it. It is a successful business. It's an important business for society. But we need to think about where we put our resources.

無論如何，我們都不是一家大公司，需要有一個重點。所以我們正在尋找適合它的商業模式。這是一個成功的企業。這對社會來說是一項重要的業務。但是我們需要考慮我們把資源放在哪裡。

When you look at the cost base, it's not just a question I found in the company about how much we spend, but how we spend it. And there have been a number of pet projects around and other areas where we're spending money.

當你查看成本基礎時，我在公司中發現的問題不僅僅是我們花了多少錢，而是我們如何花錢。周圍有許多寵物項目以及我們正在花錢的其他領域。

And I think one of the things I'm really trying to drive is focus in the company. What really matters, what's going to grow the business and how do we align our resources behind that? And whatever is not one of the major growth drivers, I think we have to look carefully at whether we continue to either to support that business with resources or we think about other options for some of those businesses.

我認為我真正想要推動的事情之一是專注於公司。真正重要的是什麼會促進業務增長，我們如何在這背後調整我們的資源？無論是不是主要的增長動力之一，我認為我們都必須仔細考慮我們是繼續用資源支持該業務，還是為其中一些業務考慮其他選擇。

Our next question comes from the line of Umer Raffat of Evercore.

我們的下一個問題來自 Evercore 的 Umer Rafat。

I wanted to touch up on the infusion capacity a little bit in a little more detail. I feel like we've talked about it several times that infrastructure needs to be built out, but could we quantify, for example, of the 100,000 patients number mentioned in some of the prior press releases for year 3, how much of that exists today? And could you take an interim look in your ongoing EARLY AD study where you have a monthly arm to perhaps update the label towards monthly. Could that happen anytime soon?

我想更詳細地談談輸液能力。我覺得我們已經多次討論過需要建設基礎設施，但我們能否量化，例如，在之前的一些新聞稿中提到的第 3 年的 100,000 名患者人數中，今天有多少？ ？您能否臨時查看正在進行的 EARLY AD 研究，在該研究中您有一個每月一次的手臂，也許可以將標籤更新為每月一次。這會很快發生嗎？

So on the capacity, obviously, Biogen had worked quite -- made quite a bit of progress on that for the launch of ADUHELM. And so I would say we're probably in better shape today than when we were at the launch of ADUHELM.

因此，在能力方面，顯然，百健（Biogen）在推出 ADUHELM 方面取得了相當大的進展。所以我想說我們今天的狀態可能比我們推出 ADUHELM 時更好。

Nonetheless, it's not like there are a lot of empty infusion centers waiting for Alzheimer's patients today. So there is going to have to be continued investment, and it will take time. And I think one of the reasons that we have guided to 100,000 patients is that it's just going to -- they're going to be constraints to the system.

儘管如此，今天並沒有很多空輸液中心在等待阿爾茨海默病患者。因此，將不得不繼續投資，這需要時間。我認為，我們指導 100,000 名患者的原因之一是，他們將成為系統的限制因素。

There's not a lot of point talking about what's the potential, how many Alzheimer's patients out there and how many are eligible, there are natural constraints to this. There's also going to have to be a careful selection of patients as to who's really the best patient to benefit from this treatment and physicians will take their time to understand this new therapy and get experience with the drug.

談論潛力是什麼、那裡有多少阿爾茨海默氏症患者以及有多少人符合條件並沒有太多意義，這有自然的限制。還必須仔細選擇患者，以確定誰是最適合從這種治療中獲益的患者，醫生將花時間了解這種新療法並獲得使用該藥物的經驗。

So it's going to be slow, steady progress. I can't give you -- I wouldn't want to comment today on how many sites, but it is something that is obviously a major part of this launch. That's why I say it's not really a round white tablet as the launch.

所以這將是緩慢而穩定的進展。我不能給你——我今天不想評論有多少網站，但這顯然是這次發布的主要部分。這就是為什麼我說它不是真正的圓形白色平板電腦作為發布。

And I think the other question was around potentially less frequent maintenance dosing the timeline for that. Priya, do you want to comment?

而且我認為另一個問題是可能不太頻繁的維護時間線。 Priya，你想發表評論嗎？

Sure. So yes, exactly right, Chris. I think we've also -- we also think that some of this infusion capacity could be elastic, and we'll have early learnings. So I think as you said, we'll learn as we go.

當然。所以是的，完全正確，克里斯。我認為我們也 - 我們也認為這種注入能力中的一些可能是有彈性的，我們將有早期的學習。所以我認為正如你所說，我們會邊走邊學。

Two points here. One is that Eisai is already leading on developing a maintenance therapy. And this could be either a 4-week or a 12-week dosing paradigm. They have said publicly that they will file for this by Q1 2024. That's important.

這裡有兩點。一是衛材已經在開發一種維持療法方面處於領先地位。這可以是 4 週或 12 週的給藥範例。他們公開表示，他們將在 2024 年第一季度之前提交申請。這很重要。

The other aspect, I think, that is also in development is a subcutaneous formulation. And I think we are -- Eisai and Biogen are thinking about what burden it would -- a product like LEQEMBI have and how do we solve that for patients as well as providers, and that is really the strategy behind the subcutaneous development.

我認為，另一方面也在開發中的是皮下製劑。我認為我們 - 衛材和百健（Biogen）正在考慮它會帶來什麼負擔 - 像 LEQEMBI 這樣的產品以及我們如何為患者和提供者解決這個問題，這實際上是皮下開發背後的戰略。

It's being studied currently in a Phase III sub-study, and it will also be filed by Q1 2024 as Eisai has communicated. So I think we're trying to work from multiple perspectives here, and we'll share more updates as they become relevant.

它目前正在 III 期子研究中進行研究，正如衛材所傳達的那樣，它也將在 2024 年第一季度提交。因此，我認為我們正在嘗試從多個角度開展工作，並且我們將在它們變得相關時分享更多更新。

Our next question comes from Evan Seigerman of BMO.

我們的下一個問題來自 BMO 的 Evan Seigerman。

So Chris, in your remarks, you highlighted a shift in business development, whereas in the past, Biogen may have been more hesitant to acquire, where would you like to focus BD? And what size deals would you be comfortable with?

所以克里斯，在你的發言中，你強調了業務發展的轉變，而在過去，百健（Biogen）可能更猶豫要收購，你想把 BD 的重點放在什麼地方？您願意接受多大的交易？

From a management point of view, you have to think about what is your -- what's your team good at? And what's interesting about Biogen is it's been a very narrowly focused company. They've been very good on what has been done in multiple sclerosis, for example, but you have to think carefully about how broadly you go because we are extremely good at selling high-value, low-volume products.

從管理的角度來看，你必須考慮你的 - 你的團隊擅長什麼？百健（Biogen）的有趣之處在於它一直是一家專注範圍非常狹窄的公司。例如，他們在多發性硬化症方面做得很好，但你必須仔細考慮你的範圍，因為我們非常擅長銷售高價值、小批量的產品。

And even as we contemplate the zuranolone launch, we are going to be going to a much broader population. We're probably going to have a lot more patient outreach. I think Biogen has done exactly on television commercial in its history. And that's something we're going to have to get good at. So as you think about business development, you have to think about, okay, you can potentially look at things on paper, but can you execute well on them?

即使在我們考慮推出 zuranolone 時，我們也將面向更廣泛的人群。我們可能會有更多的耐心外展。我認為百健（Biogen）在其歷史上已經完全在電視廣告上做過。這是我們必須擅長的事情。所以當你考慮業務發展時，你必須考慮，好吧，你可以在紙上看東西，但你能很好地執行它們嗎？

Now when I look at it, I say, I'd like to be a little bit broader than the traditional neurodegenerative diseases because I don't want to abandon them by any means, but if your only business is that, you are really destined to do these long-term studies that are highly costly and often the Phase III becomes the proof of concept because you can't really test these things adequately in Phase II.

現在當我看著它時，我說，我想比傳統的神經退行性疾病更廣泛一點，因為我不想以任何方式放棄它們，但如果你唯一的事情就是那樣，你真的注定進行這些成本高昂的長期研究，通常第三階段成為概念的證明，因為你無法在第二階段真正充分地測試這些東西。

And so if I sort of say, "Well, where could we legitimately go? Where do we have some experience?" Well, we can certainly be in immunology because I would argue that things like lupus, where we already are, even multiple sclerosis is really an autoimmune disease. So I can see us branching out more into immunology.

所以如果我說，“好吧，我們可以合法地去哪裡？我們在哪裡有一些經驗？”好吧，我們當然可以從事免疫學研究，因為我認為像狼瘡這樣的疾病，我們已經身處其中，甚至多發性硬化症也確實是一種自身免疫性疾病。所以我可以看到我們更多地涉足免疫學。

Psychiatry will have one product in the bang with zuranolone, would make sense to expand more into psychiatry. And obviously, with SPINRAZA, when we look at how do we get more out of SPINRAZA? When you're in the rare disease business, it's different than most other businesses. Most other therapeutic areas, you go see a physician because the patients go to the physician.

精神病學將有一種產品與 zuranolone 相得益彰，進一步擴展到精神病學是有意義的。顯然，對於 SPINRAZA，當我們研究如何從 SPINRAZA 中獲得更多收益時？當您從事罕見病業務時，它與大多數其他業務不同。大多數其他治療領域，你去看醫生，因為病人去看醫生。

In rare diseases, you have to go find the patient. I remember at Genzyme, someone in marketing teaching me very early on that the marketing strategy is looking for needles in haystack. And that actually becomes a core competency. And that's one of the areas that we have to go after because it's an awful lot of easier-to-find patients who are more serious and are naturally visiting physicians.

在罕見病中，你必須去找病人。我記得在 Genzyme，營銷人員很早就教我營銷策略是大海撈針。這實際上成為了一項核心競爭力。這是我們必須追求的領域之一，因為有很多更容易找到的病人，他們更嚴重，自然會去看醫生。

But there are, for instance, adult patients who are difficult to diagnose. And so looking at increasing the patient numbers means that we're going to have to be good at rare diseases. And once you have that core competency, in my view, you can be in rare disease and you can be therapy or indication-agnostic in that area.

但是，例如，有些成年患者很難診斷。因此，著眼於增加患者數量意味著我們必須擅長治療罕見病。在我看來，一旦你擁有了這種核心能力，你就可以治療罕見病，並且可以在該領域成為治療或適應症不可知論者。

So that's where we're starting because I think we can execute in those areas. Could that be acquisition, could be late stage in licensing. We could look at all of the above. And I -- look, Biogen hasn't necessarily looked at acquisitions as part of its growth strategy.

這就是我們開始的地方，因為我認為我們可以在這些領域執行。那可能是收購，可能是許可的後期階段。我們可以看看以上所有內容。我——看，百健（Biogen）不一定將收購視為其增長戰略的一部分。

Equally, I tell people, there wasn't a lot of point hiring me if you don't want to go do deals. So not to say we are, but I think there is now an openness within the company to at least look at it.

同樣，我告訴人們，如果你不想做交易，僱用我也沒什麼意義。所以並不是說我們是，但我認為公司內部現在有一種開放的態度，至少可以看看它。

Now as we all know, M&A is hard to execute on and get something that is truly accretive and generates a return on investment. And that's why we are really focused, first and foremost, on driving the most that we can out of organic growth. But I would say that we are open to anything in those 4 areas that I mentioned before.

現在眾所周知，併購很難執行並獲得真正增值並產生投資回報的東西。這就是為什麼我們首先真正專注於最大限度地推動有機增長。但我要說的是，我們對我之前提到的那 4 個領域的任何事情都持開放態度。

And I'll just quickly add, Evan, to your question on size of deals, without commenting on how large a deal we might do or a series of deals just in terms of aggregate capacity. As we mentioned up front, we ended the year with $5.6 billion in cash, we have more coming in from Samsung in the early second quarter of this year, and we have a modest amount of debt. So you can pretty quickly get to a close to better part of $10 billion of capacity number that we can utilize in a variety of ways.

埃文，我會快速補充你關於交易規模的問題，而不會評論我們可能會做多大的交易或僅就總容量而言的一系列交易。正如我們前面提到的，我們在今年年底擁有 56 億美元現金，今年第二季度初我們從三星獲得了更多現金，而且我們的債務數額不大。因此，您可以很快獲得 100 億美元容量中的大部分，我們可以通過多種方式利用這些容量。

Point out the amount of money we're getting still from Samsung on the yet to come in?

指出我們還沒有從三星那裡得到多少錢？

Yes, $800 million that's coming in April and then another $400 million-plus that will come in next year.

是的，4 月份將投入 8 億美元，明年將投入 4 億美元以上。

Firepower is not necessarily the main constraint finding something that's worthwhile doing is the really hard part of this.

火力不一定是主要的製約因素，找到值得做的事情才是真正困難的部分。

We will now move to Tim Anderson of Wolfe Research.

我們現在將轉到 Wolfe Research 的 Tim Anderson。

A couple of questions on LEQEMBI and the subcu. Can you just confirm what the minimum regulatory requirements are for approval of a subcu in terms of what you need to show in the data you're currently capturing? And do you think there's any meaningful risk in gathering that necessary data?

關於 LEQEMBI 和 subcu 的幾個問題。您能否就您需要在當前捕獲的數據中顯示的內容確認批准 subcu 的最低監管要求是什麼？您認為收集必要數據是否存在任何有意義的風險？

To me, the long-term commercial future of the brand really hinges on having a subcu, and I'm trying to gauge whether there's any meaningful risk that we should be cognizant of?

對我來說，該品牌的長期商業未來真的取決於是否有一個 subcu，我正在嘗試衡量是否存在任何我們應該意識到的有意義的風險？

I can take that. Thanks for that question. I think overall, I just want to reiterate that Eisai is studying subcutaneous in the Phase III open-label extension. And actually, details of that substudy are public. You can take a look at that. Eisai has also communicated that they believe that they have had the regulatory discussions to embark upon this pathway.

我可以接受。謝謝你的問題。我認為總的來說，我只想重申，衛材正在 III 期開放標籤擴展中研究皮下注射。實際上，該子研究的細節是公開的。你可以看看那個。衛材還表示，他們相信他們已經進行了監管討論以走上這條道路。

But beyond that, it would be speculative to say what are the minimum requirements. I think we do have regulatory discussions ongoing and a lot, as you know, is always dependent on the data as it gets generated.

但除此之外，說什麼是最低要求將是推測性的。我認為我們確實正在進行監管討論，而且如您所知，很多內容始終取決於生成的數據。

Overall, Eisai has communicated that they will -- they expect to file by Q1 2024. And then stepping back to what is the true potential. We -- I'll just draw us back to the data that we saw from the Clarity AD study, which was, of course, utilizing the intravenous bimonthly dosing regimen.

總體而言，衛材已表示他們將——他們希望在 2024 年第一季度提交申請。然後回到真正的潛力。我們——我只想讓我們回到我們從 Clarity AD 研究中看到的數據，該研究當然是使用靜脈雙月給藥方案。

I think the most important part there was that we saw the amyloid reduction at 6 months expanding over the 18-month period, we had a positive primary endpoint with a highly statistically significant p-value as well as all the secondary end points. So we believe that really Clarity AD is quite clear in its outcome, and we believe that the data are meaningful and can have an impact on the patient population.

我認為最重要的部分是我們看到 6 個月時澱粉樣蛋白的減少在 18 個月期間擴大，我們有一個積極的主要終點，具有高度統計意義的 p 值以及所有次要終點。因此，我們相信 Clarity AD 的結果非常明確，我們相信這些數據是有意義的，可以對患者群體產生影響。

The subcutaneous formulation is really our approach to kind of thinking about this more comprehensively. So we believe as it has a lot of potential and then, of course, we'll continue to build on what is the dosing, maintenance dosing as well as subcutaneous.

皮下製劑確實是我們更全面地思考這個問題的方法。所以我們相信它有很大的潛力，然後，當然，我們將繼續建立劑量、維持劑量以及皮下給藥。

And as Chris mentioned, what is the application of an anti-amyloid therapy in presymptomatic or preclinical Alzheimer's disease.

正如克里斯提到的，抗澱粉樣蛋白療法在症狀前或臨床前阿爾茨海默病中的應用是什麼。

Tim, the way I look at this is, I think what we're going to see over time is that you're going to have a plaque removal phase of treatment and then a maintenance. And in the short term, we can talk about potential for subcu, but really, I would say for the next 2 to 3 years, the demand for the product is probably more limited by capacity of the system to actually diagnose and treat patients.

蒂姆，我對此的看法是，我認為隨著時間的推移我們將看到的是你將進行一個去除斑塊的治療階段，然後是一個維護階段。在短期內，我們可以談論 subcu 的潛力，但實際上，我想說在未來 2 到 3 年內，對該產品的需求可能更多地受到系統實際診斷和治療患者的能力的限制。

So an IV will be a port for the convenience of patients, but I'm not sure that short-term, it's really going to have that much impact on demand. One game-changer, I think, to me is blood biomarkers. If we can eliminate the PET scans and in particular or the lumbar puncture, this will make it a whole lot easier for the whole medical community to at least get the diagnosis, and we can probably reduce the overall treatment cost of a patient.

所以 IV 將成為方便患者的一個端口，但我不確定短期內，它真的會對需求產生那麼大的影響。我認為，對我來說，改變遊戲規則的一個因素是血液生物標誌物。如果我們可以取消 PET 掃描，尤其是腰椎穿刺，這將使整個醫學界至少更容易得到診斷，而且我們可能會降低患者的總體治療成本。

Those blood biomarkers have been around for some time, but until there was a treatment, there wasn't a commercial market for those diagnostics. So to me, the biggest game-changer that could occur is if we can get some of these blood diagnostics to market sooner. It's -- they're probably still a couple of years away. But they're as important, in my mind, commercially as a subcu.

那些血液生物標誌物已經存在了一段時間，但在出現治療之前，這些診斷沒有商業市場。所以對我來說，可能發生的最大的改變遊戲規則的是，如果我們能更快地將其中一些血液診斷產品推向市場。這是——他們可能還需要幾年時間。但在我看來，它們在商業上與 subcu 一樣重要。

We will now take your question from Brian Abrahams of RBC Capital Markets.

我們現在將從 RBC Capital Markets 的 Brian Abrahams 那裡回答你的問題。

On LEQEMBI, as you consider the maintenance therapy, what's the right way we should be thinking about the potential balance of annual per patient price declines versus the potential for market expansion and greater durability for chronic use?

在 LEQEMBI 上，當你考慮維持治療時，我們應該以什麼正確的方式來考慮每年每位患者價格下降與市場擴張潛力和長期使用更持久性之間的潛在平衡？

You mean the price decline related to maintenance, is that what you're saying?

您的意思是與維護相關的價格下降，是您的意思嗎？

Like, I guess, how are you thinking about pricing strategically for a maintenance therapy on an annualized basis relative to the every 2 week, and how should we think about the overall balance?

就像，我想，你如何考慮相對於每 2 週一次的年化維持治療的戰略定價，我們應該如何考慮整體平衡？

Again, I think as -- obviously, we have to wait now and see the data and get approval for these things. But I think you're probably going to be in this plaque removal process, and that's the every 2 weeks. As you get into maintenance, as Priya said, the dosing regimen could change. And obviously, if you were to go from 2 weeks to 1 month, that has an overall per patient cost on an annualized basis that would be lower.

同樣，我認為 - 顯然，我們現在必須等待，查看數據並獲得對這些事情的批准。但我認為您可能會參與這個牙菌斑清除過程，而且是每 2 週一次。正如 Priya 所說，當您進入維護階段時，給藥方案可能會發生變化。顯然，如果您要從 2 週縮短到 1 個月，那麼按年計算，每位患者的總體成本會更低。

So I think you'll see potentially a lower patient cost just because of the different dosing regimen over time. Shorter term, again, I think we probably have more patients out there than the system can manage. And so I don't think there's going to be that much price pressure.

所以我認為你會看到潛在的較低的患者成本只是因為隨著時間的推移不同的給藥方案。從短期來看，我認為我們可能有更多的病人，超出了系統的管理能力。所以我認為不會有那麼大的價格壓力。

Once the system adapts, there may be over time, but I don't really see prices being the main aspect of this. And remember, when you look at this -- I mean, we're talking about $26,500 for the drug cost. But there's a lot more cost to the system for the treatment of the patients. A PET scan, for instance, costs around $7,000 as an example, and you have the MRIs and you have the treatment.

一旦系統適應，可能會隨著時間的推移而變化，但我並不真正認為價格是其中的主要方面。請記住，當你看到這個時——我的意思是，我們談論的是 26,500 美元的藥品費用。但是該系統用於治療患者的成本要高得多。例如，PET 掃描的費用約為 7,000 美元，並且您擁有 MRI 和治療。

And that's why, to me, blood diagnostics could play a bigger role in actually reducing the overall cost. And I think those types of things, and as we move into maintenance dosing regimen, we may find that the average annual cost of a patient goes down, although we're not necessarily touching the price of the drug.

這就是為什麼對我來說，血液診斷可以在實際降低總體成本方面發揮更大的作用。我認為這些類型的事情，當我們進入維持劑量方案時，我們可能會發現患者的平均年度費用下降，儘管我們不一定會觸及藥物的價格。

We will now take a question from Michael Yee of Jefferies.

我們現在將接受 Jefferies 的 Michael Yee 的提問。

You mentioned in the slides that you would like to improve the risk profile and productivity, R&D pipeline, particularly profile. And I recall, in January, you talked about lower-risk-type projects and perhaps Biogen is too high risk, high reward, particularly for this market cap? And then going back to your prior days, you did, I think, the Genzyme deal and the Regeneron deal.

您在幻燈片中提到您希望改善風險狀況和生產力、研發渠道，尤其是概況。我記得，在一月份，你談到了低風險類型的項目，也許百健（Biogen）風險太高，回報太高，尤其是對於這個市值？然後回到你之前的日子，我認為你做了 Genzyme 交易和 Regeneron 交易。

So can you just comment about the philosophy of bringing in products that are perhaps lower risk, more derisked and how you think about bringing those in and acting on those accordingly and with the speed?

那麼，您能否評論一下引入風險較低、風險更高的產品的理念，以及您如何考慮引入這些產品並相應地快速採取行動？

Sure. To me, risk management is something that is part of the day job in a pharma company. You obviously, can't do anything unless you take risk. We develop products in early stage. If you're talking about Phase I, you've got 10% probability of success. I think there's a couple of areas that we would look at.

當然。對我來說，風險管理是製藥公司日常工作的一部分。很明顯，除非你冒險，否則你什麼也做不了。我們在早期開發產品。如果你談論的是第一階段，你有 10% 的成功概率。我認為我們會關注幾個領域。

The first thing is, obviously, if you can do a Phase II study where you get a lot of confidence out of safety and efficacy before you go into a Phase III study, you have essentially, at every stage of development, from Phase I to Phase II, Phase II to Phase III derisk that.

顯然，第一件事是，如果你能進行 II 期研究，在進入 III 期研究之前，你對安全性和有效性有很大的信心，那麼你基本上在從 I 期到第二階段，第二階段到第三階段對此表示懷疑。

We sometimes can't do it. If you look at Alzheimer's and the development of either lecanemab or ADUHELM, you can start to see, for instance, that you're reducing plaque, but one of the problems we -- a lot of companies had is that they didn't reduce the plaque enough, and you're not going to know whether you have reduced the plaque enough until you see a benefit in cognitive function.

我們有時做不到。如果你看看阿爾茨海默氏症和 lecanemab 或 ADUHELM 的開發，你可以開始看到，例如，你正在減少斑塊，但我們 - 許多公司遇到的問題之一是他們沒有減少斑塊減少得足夠多，直到您看到認知功能的益處，您才會知道您是否已經充分減少了斑塊。

But you really can't do that until you go into large studies and take a long time because these diseases progress so slowly. So to me, one of the areas is that we can -- if you go into autoimmune diseases or you're into psychiatry, you can have a more classical drug development where you can derisk more in Phase II, you can get a proof of concept.

但是，除非你進行大規模研究並花費很長時間，否則你真的無法做到這一點，因為這些疾病的進展非常緩慢。所以對我來說，其中一個領域是我們可以——如果你進入自身免疫性疾病或你進入精神病學，你可以進行更經典的藥物開發，你可以在第二階段降低更多風險，你可以獲得證據概念。

As I said earlier, we are sometimes doing proof of concept in Phase III, which is an expensive way to do proof of concept. So just even thinking about moving into some of these other areas allows us to do more classical drug development. The other is, of course, that we can start to license in products and that are a lot closer to market, and you're not taking quite as much risk on those.

正如我之前所說，我們有時會在第三階段進行概念驗證，這是進行概念驗證的一種昂貴方式。因此，即使只是考慮進入其他一些領域，我們也可以進行更多的經典藥物開發。另一個當然是，我們可以開始對產品進行許可，這些產品更接近市場，而且你不會在這些產品上承擔那麼大的風險。

But it's really a function of when you look at it, how much are precedented versus unprecedented mechanism of action? How much are small molecules versus large molecules? Can we do more collaborative-type approaches?

但它實際上是一個功能，當你看它時，有多少先例和前所未有的行動機制？小分子與大分子有多少？我們可以採用更多協作類型的方法嗎？

But this notion of always doing proof of concept in Phase III is a highly expensive, highly risky approach. And I think having a few of those projects in our pipeline is good, having 100% of our pipeline and projects like that is challenging.

但是這種總是在第三階段進行概念驗證的想法是一種非常昂貴、高風險的方法。而且我認為在我們的管道中有一些這樣的項目是好的，擁有我們 100% 的管道和項目是具有挑戰性的。

And if you look at it, we don't really have an approval coming in our pipeline for several years yet here because we're waiting on these long-term studies. So having things that read out on a little bit more frequent basis would be helpful to looking at sustainable growth of the company.

而且，如果您看一下，我們在這裡幾年還沒有真正獲得批准，因為我們正在等待這些長期研究。因此，更頻繁地宣讀一些內容將有助於審視公司的可持續發展。

Operator, I think we have time for 1 final question.

接線員，我想我們有時間問最後一個問題。

Our next question comes from Chris Schott of JPMorgan.

我們的下一個問題來自摩根大通的克里斯肖特。

Just another 1 on BD. Is this something you're going to be looking to do in parallel with your strategic review and cost resizing efforts? Or is this a bit of a longer-term priority once you make whatever changes are necessary for the core business?

BD 上的另一個 1。這是您打算在戰略審查和成本調整工作的同時進行的事情嗎？或者，一旦您對核心業務做出任何必要的改變，這是否是一個更長期的優先事項？

And maybe just a second part of that same question. Given your prior comments of the narrow focus of Biogen, does that point more towards BDs skewed towards either company acquisitions versus partnerships or earlier-stage deals because it seems like you might want to be bringing both products as well as kind of expertise in-house? Just help me a little bit in terms of like the -- how you think about that dynamic?

也許只是同一個問題的第二部分。鑑於您之前對百健（Biogen）關注範圍狹窄的評論，這是否更傾向於 BD 偏向於公司收購與合作夥伴關係或早期交易，因為看起來您可能希望將這兩種產品以及某種專業知識引入內部？請幫我一點點——你如何看待這種動態？

I think certainly for the first half of this year, we're focused on really reorienting the company towards these growth opportunities, looking at the cost base. We should have a new Head of Research in that timeframe.

我認為在今年上半年，我們確實專注於重新調整公司的方向，以迎接這些增長機會，著眼於成本基礎。我們應該在那個時間段內有一個新的研究主管。

We're also in the process of recruiting a Head of BD. So to me, this is sort of something that we start to look at in the second half of the year. As you know, it takes a while to go find things. You've got to look at a lot of things before you do something.

我們也在招聘 BD 負責人。所以對我來說，這是我們在今年下半年開始關注的事情。如您所知，尋找東西需要一段時間。在你做某事之前，你必須看很多東西。

So even if you decide you want to do something next year, you really have to start looking now. In terms of what we're looking at? Look, it could be all of the above. To the degree that we get comfortable with the launch trajectory of LEQEMBI and zuranolone, you could argue that the bankers like to refer to this desperation factor.

因此，即使您決定明年要做某事，您也確實必須現在就開始尋找。就我們正在看的東西而言？看，可能是以上所有情況。就我們對 LEQEMBI 和 zuranolone 的發射軌跡感到滿意的程度而言，你可以爭辯說銀行家喜歡提到這種絕望因素。

I would argue that we don't have a high desperation factor. We actually have a lot that we can do within the company. I think it's healthy to be looking outside and to always have options because in this business, nothing ever goes completely to plan. But we have the time to look and make sure that whatever we do is going to be value-added, and I think it could be all of the things that you've mentioned.

我認為我們沒有很高的絕望因素。實際上，我們在公司內部可以做很多事情。我認為向外看並始終有選擇是健康的，因為在這個行業中，沒有什麼事情會完全按計劃進行。但我們有時間研究並確保我們所做的一切都會增值，我認為這可能是你提到的所有事情。

Okay. With that, I think we're going to conclude the call for today. Thank you, everyone, for joining us.

好的。至此，我想我們將結束今天的電話會議。謝謝大家加入我們。

This concludes today's call. Thank you for your participation. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。