Biogen Inc (BIIB) 2024 Q4 法說會逐字稿

Good morning.

早安.

My name is Jennifer, and I will be your conference operator today.

我叫詹妮弗，今天我將擔任您的會議主持人。

At this time, I'd like to welcome everyone to the Biogen fourth-quarter and full-year 2024 earnings call and business update.

現在，我歡迎大家參加 Biogen 第四季和 2024 年全年財報電話會議和業務更新。

(Operator Instructions) Today's conference is being recorded.

（操作員指示）今天的會議正在錄音。

Thank you.

謝謝。

I would now like to turn the conference over to Mr. Tim Power, Head of Investor Relations.

現在，我想將會議交給投資者關係主管 Tim Power 先生。

Mr. Power, you may begin your conference.

鮑爾先生，您可以開始您的會議了。

Thanks, Jennifer, and good morning, and welcome to Biogen's fourth-quarter and full-year 2024 earnings call.

謝謝，詹妮弗，早上好，歡迎參加 Biogen 2024 年第四季和全年財報電話會議。

During this call, we'll make forward-looking statements, which involve risks and uncertainties that may cause actual results to differ materially from our forward-looking statements.

在本次電話會議中，我們將做出前瞻性陳述，其中涉及風險和不確定性，可能導致實際結果與我們的前瞻性陳述有重大差異。

We provide a comprehensive list of risk factors in our SEC filings, which I encourage you to review.

我們在美國證券交易委員會 (SEC) 文件中提供了全面的風險因素列表，我鼓勵您查看。

Our earnings release and other documents related to our results as well as reconciliations between GAAP and non-GAAP results discussed on this call can be found in the Investors section of biogen.com. We've also posted slides on our website that we will be using during the call.

我們的收益報告和與我們的業績相關的其他文件以及本次電話會議討論的 GAAP 和非 GAAP 結果之間的對帳可在 biogen.com 的投資者部分找到。我們還在我們的網站上發布了我們將在通話期間使用的幻燈片。

On today's call, I'm joined by our President and Chief Executive Officer, Chris Viehbacher; Dr. Priya Singhal, Head of Development; and Mike McDonnell, Chief Financial Officer.

在今天的電話會議上，我與我們的總裁兼執行長 Chris Viehbacher 一起出席； Priya Singhal 博士，開發主管；以及財務長 Mike McDonnell。

We'll make some opening comments and then move to Q&A.

我們將做一些開場評論，然後進入問答環節。

And to allow us to get through as many questions as possible, we'll kindly ask that you limit yourself to just one question.

為了讓我們能夠解答盡可能多的問題，我們懇請您將問題限制在一個範圍內。

And with that, I'll hand over to Chris.

現在我將把麥克風交給克里斯。

Thank you, Tim.

謝謝你，提姆。

Good morning, everybody.

大家早安。

Perhaps before we get started, I'd just like to note that this is Mike McDonnell's last quarterly presentation as CFO of Biogen.

在我們開始之前，我可能想指出這是 Mike McDonnell 作為 Biogen 財務長的最後一次季度報告。

Mike, I believe this is your 97th quarter as a publicly quoted CFO.

麥克，我相信這是您擔任上市公司財務長的第 97 季。

So congratulations on that amazing career and I'll just take the opportunity to thank you.

所以恭喜你擁有如此出色的職業生涯，並藉此機會向你表示感謝。

You've been a terrific partner and team member, and it's been great working with you, and we will miss you.

您是一位出色的合作夥伴和團隊成員，與您共事非常愉快，我們會想念您的。

And we of course are joined here also by Robin Kramer.

當然，我們還有羅賓克萊默 (Robin Kramer) 的參與。

I'm also proud to say that we've been able to promote from within, and it's a great source of pride that we have that level of talent within the organization.

我還自豪地說，我們能夠從內部提拔人才，我們組織內擁有如此水準的人才，這是我們最大的自豪。

So let's turn to Q4.

那麼讓我們轉到 Q4。

As you all know, we have been faced with increased competition for our multiple sclerosis franchise.

眾所周知，我們的多發性硬化症特許經營面臨日益激烈的競爭。

And really, all of our priorities are thinking about how do we now build a new Biogen, how do we build a new phase of growth.

事實上，我們所有的首要任務都是思考如何打造一個新的 Biogen，如何建構一個新的成長階段。

And we are focused really around three core priorities.

我們真正關注的是三個核心重點。

The first are clearly the four products that we launched last year in Alzheimer's, Friedreich's ataxia, depression, and ALS.

首先顯然是我們去年推出的針對阿茲海默症、弗里德賴希共濟失調、憂鬱症和 ALS 的四種產品。

Each of those products is not only first-in-class, but first disease-modifying agent in each of these diseases.

這些產品不僅是同類產品中的首創，也是針對每種疾病的首個疾病改良劑。

Now that's a source of pride in the level of innovation that Biogen is capable of.

這就是 Biogen 創新水準值得驕傲的地方。

But equally, from a commercial point of view, this is a significant challenge since the level of education when you're a pioneer in an area is so much greater, and we'll come back and talk a little bit more about that.

但同樣，從商業角度來看，這是一個重大挑戰，因為當你作為某個領域的先驅者時，所受的教育水平要高得多，我們將回過頭來進一步討論這一點。

The next is we have really reprioritized the pipeline.

接下來我們確實重新調整了管道的優先順序。

It's certainly been my experience over the years that focusing on a number of key projects is core to business success.

根據我多年的經驗，專注於一些關鍵項目是企業成功的核心。

And I'm pretty grateful to both Priya Singhal and Jane Grogan because they have both really, I think, cleaned out the pipeline for development in Priya's case; in research, in Jane's case.

我非常感謝 Priya Singhal 和 Jane Grogan，因為我認為她們確實為 Priya 的案例清理了發展渠道；就簡的情況而言，這是在研究中。

And we're actually excited now by the products that are in there.

我們現在確實對裡面的產品感到非常興奮。

We've got a number of key developments that will start reading out in 2026.

我們有許多關鍵進展將於 2026 年開始公佈。

We think this is a multibillion-dollar portfolio.

我們認為這是一個價值數十億美元的投資組合。

And we're probably one of the few companies that can look at a pipeline that could be more than our current biopharmaceutical business when it gets to peak sales if it all, obviously, comes to market.

而且，我們可能是為數不多的能夠考慮在產品線中增加更多產品線的公司之一，如果所有產品都進入市場，當銷售達到高峰時，我們的產品線可能會比目前的生物製藥業務還要大。

The third point, of course, is we have redesigned the company with a reduction of operating expenses, not just saving costs for the sake of cost but the ability to release resources for investing in growth, and that's what we're continuing to do.

第三點當然是我們對公司進行了重新設計，降低了營運費用，不僅是為了成本而節省成本，而且能夠釋放資源用於投資成長，這也是我們正在繼續做的事情。

We're excited about our pipeline, but we've also freed up an awful lot of cash flow, as you'll see later.

我們對我們的管道感到非常興奮，但我們也釋放了大量的現金流，正如您稍後將看到的那樣。

And that cash flow, we're investing for more substrate in growth.

我們將利用這些現金流來為成長提供更多的基礎。

So yes, now, Dan, please next slide.

是的，現在，丹，請看下一張投影片。

So the rates really that we are faced with is seeing the erosion of our multiple sclerosis product revenue but I'm particularly happy to see in 2024 that the revenue from our launch products really more than offset the decline in our multiple sclerosis product revenue.

因此，我們面臨的實際問題是多發性硬化症產品收入的下降，但我特別高興地看到，在 2024 年，我們推出的產品的收入確實超過了多發性硬化症產品收入的下降。

And indeed, when you actually look that total revenue declined by $160 million.

事實上，如果你仔細觀察就會發現，總收入下降了 1.6 億美元。

And you note that contract manufacturing declined by $247 million, it meant that really our core pharma business actually grew, and that's for the first time in four years.

您會注意到合約製造業務下降了 2.47 億美元，這意味著我們的核心製藥業務實際上實現了成長，這是四年來的首次成長。

And that's really what we're all about in the near term is trying to make sure that the revenue can exceed the multiple sclerosis product decline.

而這確實是我們近期要做的，就是努力確保收入能夠超過多發性硬化症產品的下降。

Multiple sclerosis product decline is obviously driven by a number of factors going forward, including the timing of the TYSABRI biosimilar in the US and timing of TECFIDERA generics in Europe.

多發性硬化症產品的衰退顯然受到未來多種因素的影響，包括 TYSABRI 生物相似藥在美國上市的時間安排以及 TECFIDERA 仿製藥在歐洲上市的時間安排。

Go to the next slide, please, Dan.

丹，請翻到下一張投影片。

So as I said, we've got actually four very innovative pioneering products.

正如我所說，我們實際上有四款非常創新的先鋒產品。

LEQEMBI will come on and talk about it in some detail.

LEQEMBI 將會詳細談論這一點。

SKYCLARYS in Friedreich's ataxia, again, very first treatment for Friedreich's ataxia.

SKYCLARYS 治療弗里德賴希共濟失調，這也是弗里德賴希共濟失調的首個治療方法。

We have been able to determine from basically medical claims data that there are approximately 4,800 patients in the US.

我們已經能夠根據基本醫療索賠數據確定美國約有 4,800 名患者。

That's about what we thought.

我們也是這麼想的。

One of the complexities is that it's harder to find these patients because you could have a primary care physician in a rural setting that has one single patient and you have to go find them.

其中一個複雜之處在於，要找到這些病人比較困難，因為農村地區的初級保健醫生可能只有一個病人，你必須去找他們。

And we're talking to primary care physicians, talking to cardiologists, talking to pediatricians.

我們正在與初級保健醫生、心臟科醫生和兒科醫生進行交談。

So it's quite a large prescriber base for a very narrow patient population.

因此，對於非常狹窄的患者群體來說，這是一個相當大的處方群體。

But that, of course, is the core of what rare diseases is.

但這當然是罕見疾病的核心。

I remember years ago, when we acquired Genzyme when I was at Sanofi and the marketing folks are saying, our marketing strategy is looking for needles and haystacks.

我記得幾年前，當我在賽諾菲任職時，我們收購了健贊（Genzyme），當時行銷人員說，我們的行銷策略就像是在尋找針和大海撈針。

And that is exactly what rare disease is all about, and it's what Biogen is also very good at.

這正是罕見疾病的意義所在，也是 Biogen 所擅長的。

And of course, today, we've got a lot more technology.

當然，今天我們擁有更多的技術。

We can use tools such as AI and genetic testing to help find those patients.

我們可以使用人工智慧和基因檢測等工具來幫助找到這些患者。

But by its very nature, it is unfortunately not going to be the nice smooth progression quarter on quarter.

但就其本質而言，不幸的是，它不會是逐季度順利進展的。

That said, we are particularly proud to say that we have been able to double the number of patients on treatment in the past year.

儘管如此，我們還是特別自豪地說，在過去的一年裡，接受治療的患者數量增加了一倍。

Not all of those are yet being reimbursed.

但並非所有這些款項都已償還。

We are able to get a lot of patients on drug and then negotiate with governments, particularly in Europe, to get the reimbursement.

我們能夠讓許多患者使用藥物，然後與政府（特別是歐洲的政府）進行談判，以獲得報銷。

And once we do that, the patients flip from being free goods patients to actually revenue-generating treatments.

一旦我們做到這一點，患者就從接受免費治療的患者變成了真正能產生收入的治療者。

There's always a bit of a -- in each country, a number of patients who are diagnosed, who have been waiting for treatment and you can get those quite easily.

每個國家都總是會有一些被診斷出患有某種疾病的病人，他們一直在等待治療，而這些病人很容易就能得到治療。

There are a number of older patients who actually have lived with this disease for 30, 40 years.

實際上，許多老年患者已經患上這種疾病 30 至 40 年了。

And they are the ones we actually have to go hunt for.

他們才是我們真正要去追捕的對象。

We will see another growth driver this year and that we expect to get approval for SKYCLARYS in Latin America.

我們今年將看到另一個成長動力，我們預計 SKYCLARYS 將獲得拉丁美洲的批准。

I was in Brazil last year and there are quite a number of patients in Latin America.

我去年去過巴西，拉丁美洲有相當多的病人。

So as we started with the US, we moved to Europe and then we're moving to South America and indeed areas of the Middle East.

因此，我們從美國開始，然後轉向歐洲，接著轉向南美，最後是中東地區。

We expect to see continued steady growth out of SKYCLARYS.

我們預計 SKYCLARYS 將繼續穩定成長。

But again, I appreciate that it's going to be hard for some of you to model on a quarterly basis.

但我再次意識到，對於某些人來說，按季度進行建模會很困難。

It was a very nice launch last year and certainly exceeded our expectations.

去年的發表會非常成功，確實超出了我們的預期。

One of the things that was different from our expectations was that the main prescriber's actually an OB/GYN.

與我們的預期不同的是，主要開處方的實際上是一名婦產科醫生。

We had actually been targeting originally high-prescribing psychiatrists.

我們原本的目標客戶其實是開藥量很大的精神科醫生。

We still see some of those, but as you can see, 80% of the prescriptions are driven by OB/GYNs.

我們仍然看到一些這樣的情況，但正如你所看到的，80％的處方是由婦產科醫生開的。

This is also an area where you could have potentially more people who have ever prescribed for PPD than you actually have patients.

在這個領域，開出 PPD 處方的人數可能比實際患者人數還要多。

And again, targeting and thinking about multichannel marketing and commercial approaches are extremely important.

再次強調，定位和思考多通路行銷和商業方法極為重要。

We have filed in Europe and would hope to see an approval sometime later this year.

我們已經在歐洲提交了申請，希望在今年稍後獲得批准。

QALSODY is not necessarily a big revenue generator, but this is really a breakthrough treatment in ALS.

QALSODY 不一定能帶來很大的收入，但它確實是 ALS 治療領域的突破。

This is the first time we've been able to demonstrate that neurofilament can really help predict drugs early in development as to whether or not they are likely to work or not.

這是我們第一次能夠證明神經絲確實可以幫助在開發早期預測藥物是否有效。

And that allows just the whole research and development in ALS to be accelerated.

這使得 ALS 的整個研究和發展得以加速。

So we're particularly proud of that.

因此我們對此特別自豪。

The impact on patients is absolutely extraordinary.

它對患者的影響絕對是非凡的。

And so while we may not be making a big impact on revenue, we're certainly making a big impact on patients' lives.

因此，雖然我們可能不會對收入產生重大影響，但我們肯定會對患者的生活產生重大影響。

Go to the next slide, please, Dan?

請翻到下一張投影片，丹？

Now I showed this slide at JPMorgan.

現在我在摩根大通展示了這張投影片。

And there were several investors who looked at that chart and said, this is not the chart of a small product.

有幾位投資人看了那張圖表後說，這不是小商品的圖表。

And we've all been in this business and looked at a lot of launch curves, and we all know that we like to see an acceleration in the curve.

我們都從事這個行業，觀察過很多發布曲線，我們都知道，我們希望看到曲線加速。

But any curve that goes from bottom left to upper right is, in my books, good unless we talk about operating expenses.

但在我看來，任何從左下角到右上角的曲線都是好的，除非我們談論營運費用。

And this is good, steady quarter-on-quarter progress.

這是良好且穩定的季度環比進展。

We have seen some questions on the ex US launch.

我們看到了一些關於美國以外發布的疑問。

Clearly, the ex US launch is contributing more than we have seen in prior launches in other areas.

顯然，這次美國以外的發射貢獻比我們之前在其他地區看到的要大。

I think part of that is -- first, I think Eisai is extremely strong in Asia and they are leading that launch there.

我認為部分原因是——首先，我認為衛材在亞洲非常強大，並且他們在那裡處於領先地位。

But second, I think the single-payer system removes a lot of the obstacles that we're dealing with in the US.

其次，我認為單一支付系統消除了我們在美國面臨的許多障礙。

When you have a single payer, you're not having to negotiate quite so much in terms of PET scans and MRIs and infusion beds, and that has facilitated the progress.

當你有一個單一的付款人時，你不需要在 PET 掃描、MRI 和輸液床方面進行那麼多的談判，這促進了進步。

And it's as strong in China as it is in Japan, not necessarily patient numbers, but we're seeing very strong growth in China, and that is a cash pay market.

中國和日本的現金支付市場同樣強勁，雖然不一定是患者數量，但我們看到中國的成長非常強勁，這是一個現金支付市場。

And those [two really are] a demonstration of how people value the importance of LEQEMBI.

這兩個例子確實顯示了人們如何重視 LEQEMBI 的重要性。

So we'll go to the next chart, please.

請讓我們看下一張圖表。

Now I talked about some of those obstacles and we certainly see that making this easier for both patients and physicians is going to accelerate the launch.

現在我談到了其中的一些障礙，我們當然看到，讓患者和醫生都更容易做到這一點將會加速這一進程。

And we have a number of these catalysts.

我們有許多這樣的催化劑。

The first one has already been achieved.

第一個目標已經實現。

So we have the LEQEMBI IV maintenance that's now FDA-approved.

因此，我們有了現在已獲得 FDA 批准的 LEQEMBI IV 維護。

We now have the first patients who are hitting that 18-month mark.

現在，我們迎來了第一批達到 18 個月存活期的患者。

They've cleared their plaque.

他們已經清除了牌匾。

But as the data have demonstrated, you've got to stay on treatment otherwise some forms of the plaque actually come back.

但正如數據所顯示的那樣，你必須堅持治療，否則某些形式的斑塊實際上會復發。

And we have demonstrated three-year data to show that actually staying on treatment, patients do better than those who stop treatment.

而且我們已經提供了三年的數據來表明，實際上堅持治療的患者比停止治療的患者表現更好。

And that's an important message because our competition is actually not able to say that.

這是一個重要的訊息，因為我們的競爭對手實際上還不能這麼說。

And so this is also important for the education of the disease.

所以這對疾病的教育也很重要。

It's not just about plaque clearance; it's about maintaining that clearance.

這不僅關乎清除牙菌斑；這是為了維持這種許可。

The second is really the introduction of blood-based diagnostics.

第二是真正引入基於血液的診斷方法。

Certainly, LabCorp and Quest continue to see rising sales of these diagnostics.

毫無疑問，LabCorp 和 Quest 持續見證著這些診斷產品的銷售上升。

What I think will really make a difference is getting FDA approval for some of these diagnostics with an evidence base that will give physicians the confidence to be able to confirm diagnosis without the need for a PET scan or a lumbar puncture.

我認為真正起作用的是讓 FDA 批准部分具有證據基礎的診斷方法，讓醫生有信心無需進行 PET 掃描或腰椎穿刺就能確診。

And so again, this is something that could not only facilitate the work of the neurologist, but we might also be able to see this being used increasingly to triage patients.

因此，這不僅可以方便神經科醫生的工作，而且我們還可以看到它在對患者進行分類方面的應用越來越廣泛。

Something like 50% of patients who actually managed to get into a neurologist are actually not eligible for treatment because they're too far advanced in their disease.

大約有 50% 的真正得到神經科醫生治療的患者實際上沒有資格接受治療，因為他們的病情已經到了晚期。

So if we could actually triage some of these patients, particularly at the primary care level, then we can actually get a higher quotient of patients who visit neurologists actually being eligible for treatment.

因此，如果我們實際上可以對其中一些患者進行分類，特別是在初級保健層面，那麼我們實際上可以讓更高比例的去看神經科醫生的患者真正有資格接受治療。

The subcutaneous form for maintenance, we would expect now.

我們現在期望的是皮下形式的維護。

We have a PDUFA date on August 31.

我們的 PDUFA 日期是 8 月 31 日。

That, again, will really facilitate the journey, both for the patient as well as for the physician, no longer needing the infusion beds and patients can actually take the drug from the comfort of their own home.

這再次真正方便了病人和醫生的用藥過程，不再需要輸液床，病人可以在自己舒適的家中服用藥物。

A major game changer we see as the subcutaneous for initiation, which we expect to have in the first half of next year.

我們認為一個重大的遊戲規則改變者是皮下注射的啟動，我們預計它將在明年上半年實現。

And that obviously would also facilitate that for the same reasons of not having to deal with infusion beds and patients can have that in the comfort of their own home.

顯然，出於同樣的原因，這也會促進這一點：患者不必處理輸液床，並且可以在自己舒適的家中接受治療。

The AHEAD 3-45 study is fully recruited.

AHEAD 3-45 研究已全面招募完畢。

We expect to read out in 2028.

我們預計在 2028 年讀完。

This is a landmark study because this is where we could see the promise of potentially prevention of Alzheimer's.

這是一項具有里程碑意義的研究，因為我們可以從中看到預防阿茲海默症的潛在前景。

We know that before patients actually exhibit symptoms, they've been accumulating plaques in their brains for many, many years.

我們知道，在患者真正出現症狀之前，他們的大腦中已經累積了許多年的斑塊。

And unfortunately, a lot of damage is done already by the time patients actually exhibit symptoms.

不幸的是，當患者真正出現症狀時，已經造成了極大的傷害。

So if we can get patients earlier, we think that we can actually have even better efficacy.

因此，如果我們能夠更早接收患者，我們認為我們實際上可以獲得更好的療效。

And in fact, Priya is going to show shortly, again, the low tau patients, which is a marker for earlier-stage patients.

事實上，Priya 很快就會再次展示低 tau 患者，這是早期患者的標誌。

And there, we see dramatically improved efficacy versus just the 27% on the CDR sum of boxes that was demonstrated in the CLARITY study.

我們看到了顯著的提高，而 CLARITY 研究表明 CDR 總和僅為 27%。

So next slide, please.

請看下一張投影片。

So those are the four products.

這就是四種產品。

Clearly, we're also looking at our pipeline.

顯然，我們也在關注我們的管道。

And I think there are three key areas in this to look at.

我認為有三個關鍵領域需要關注。

The first is continued investment and commitment to Alzheimer's.

首先是對阿茲海默症的持續投入和承諾。

We gather some of the top leading experts in Alzheimer's from around the world.

我們聚集了來自世界各地的一些阿茲海默症領域的頂尖專家。

They're the ones who are telling us, one, that nobody is really doing so much research in a broad area of modalities as Biogen, but the other is they are extremely excited about the opportunity to reduce tau and the impact that that could have on Alzheimer's.

他們告訴我們，一方面，沒有人真正像 Biogen 一樣在廣泛的治療領域進行如此多的研究，另一方面，他們對減少 tau 的機會以及這可能對阿茲海默症產生的影響感到非常興奮。

So Alzheimer's is going to be a core franchise for Biogen for decades to come.

因此，未來幾十年，阿茲海默症將成為 Biogen 的核心業務之一。

We had very positive data on dapirolizumab back in September.

早在九月份，我們就獲得了有關達匹羅珠單抗的非常積極的數據。

And we've already initiated the second Phase III.

我們已經啟動了第二階段的第三階段。

But we also have litifilimab in both CLE and SLE, so we got a nice lupus portfolio of assets coming along.

但是我們在 CLE 和 SLE 中也有利替利單抗，因此我們獲得了良好的狼瘡資產組合。

I'd remind everybody, yes, people are looking at a lot of potential competitors in Phase I, Phase II.

我想提醒大家，是的，人們正在關注第一階段和第二階段的許多潛在競爭對手。

But out of the dozens and dozens and dozens of molecules that entered the clinic, only three molecules have ever demonstrated a positive Phase III result, two are already in the market and the pirolizumab is the third.

但進入臨床的數十種分子中，只有三種分子在 III 期臨床試驗中取得了積極的成果，兩種分子已經上市，而吡羅珠單抗是第三種。

So we know that you can get excited about a lot of things, but it's not until you actually see Phase III results that you can really have conviction.

所以我們知道你會對很多事情感到興奮，但是直到你真正看到第三階段的結果，你才能真正確信。

But that's a potentially significant market and fits nicely with Biogen because we can take a lot of the learnings from MS and apply that to lupus.

但這是一個潛在的重要市場，並且與 Biogen 非常契合，因為我們可以藉鑑許多從 MS 中學到的經驗並將其應用於狼瘡。

And of course, the third area are really these auto antibodies.

當然，第三個領域其實是這些自身抗體。

We have our anti-CD38.

我們有抗CD38。

We expect to enter into three Phase III trials in three separate indications with antibody-mediated resistance, IgAN, the PMN, and we have very compelling Phase II results here.

我們預計將針對抗體介導抗藥性、IgAN 和 PMN 三種不同適應症進行三項 III 期試驗，並且我們在此獲得了非常令人信服的 II 期結果。

There are no guarantees any time in research and development, but I think we feel particularly excited about felzartamab and the potential that this could have in rare kidney disease.

在研發過程中任何時候都沒有任何保證，但我認為我們對 felzartamab 以及它在治療罕見腎臟病方面的潛力感到特別興奮。

And of course, then we have a whole phase of readouts coming along and I think that will become the story of Biogen as we get increasingly more data and people can gain increasing confidence and excitement -- share our excitement in our pipeline.

當然，接下來我們將迎來整個讀數階段，我認為這將成為 Biogen 的故事，因為我們獲得越來越多的數據，人們可以獲得越來越多的信心和興奮 - 分享我們對我們管道的興奮。

And so with that, I think I'm going to -- let's continue the story on R&D.

因此，我想我要──讓我們繼續講述研發的故事。

Priya, I'll turn it over to you.

普里婭，我將把它交給你。

Thank you, Chris.

謝謝你，克里斯。

Biogen's development organization had another very productive quarter.

Biogen 的開發組織又度過了一個非常有成效的季度。

We achieved several important milestones across key strategic areas for the company.

我們在公司的關鍵策略領域實現了幾個重要的里程碑。

I would like to begin with immunology where, in collaboration with UCB, as Chris mentioned, we initiated the second Phase III study for dapi-pegol in SLE.

我想從免疫學開始，正如克里斯所提到的，我們與 UCB 合作啟動了 dapi-pegol 治療 SLE 的第二階段 III 期研究。

This follows the positive readout of the first Phase III study and sharing of detailed study results as a late breaker at the ACR Annual Meeting last year.

此前，在去年的 ACR 年會上，第一階段 III 期研究取得了積極的成果，並作為最新消息分享了詳細的研究結果。

Dapi-pegol, as Chris mentioned, is only the third agent with a positive global Phase III study in SLE.

正如克里斯所提到的，Dapi-pegol 是治療 SLE 的全球 III 期研究中僅有的第三種藥物。

Additionally, felzatumab was granted orphan drug designation in the EU for both solid organ transplantation and IgA nephropathy.

此外，felzatumab 也被歐盟授予用於治療實體器官移植和 IgA 腎臟病的孤兒藥資格。

We believe this designation, which is intended to support development of treatments with significant unmet medical need, underscores the potential for felzartamab to become a meaningful new therapy for serious immune-mediated diseases like AMR, IgAN, and PMN globally.

我們相信，這項指定旨在支持開發具有重大未滿足醫療需求的治療方法，強調了 felzartamab 成為全球治療 AMR、IgAN 和 PMN 等嚴重免疫介導疾病的有意義的新療法的潛力。

In rare disease, we continued unlocking new geographies for SKYCLARYS in Friedrich's ataxia and QALSODY in SOD1-ALS.

在罕見疾病方面，我們繼續為弗里德里希共濟失調症中的 SKYCLARYS 和 SOD1-ALS 中的 QALSODY 解鎖新的地理位置。

Leveraging the results of the SKYCLARYS positive MOXIe trial, we obtained approval in Chile and currently have 13 additional regulatory filings under review.

利用 SKYCLARYS 積極的 MOXIe 試驗結果，我們在智利獲得了批准，目前還有 13 份另外的監管文件正在審查中。

This includes additional filings in Latin America, where we expect regulatory decisions this year in countries such as Brazil and Argentina as we continue our global rollout.

這包括在拉丁美洲的額外申請，隨著我們繼續全球推廣，我們預計今年巴西和阿根廷等國家將做出監管決定。

Importantly, we also took significant steps towards expanding the value of key portfolio products for patients.

重要的是，我們也採取了重要措施，擴大主要產品組合對患者的價值。

In SMA, regulatory filings for high-dose nusinersen have now been accepted in the US and EU, and we expect an FDA decision in September of this year.

在 SMA 中，美國和歐盟現在已經接受了高劑量 nusinersen 的監管備案，我們預計 FDA 將在今年 9 月做出決定。

And in Alzheimer's disease, we recently received FDA approval for LEQEMBI less frequent IV maintenance dosing.

在阿茲海默症方面，我們最近獲得了 FDA 批准，可使用 LEQEMBI 較低頻率的靜脈維持劑量治療。

This is both a significant step for LEQEMBI and a meaningful advancement in the evolution of Alzheimer's treatment more broadly.

這既是 LEQEMBI 邁出的重要一步，也是阿茲海默症治療領域更廣泛發展的重大進步。

I would like to briefly review why there is an urgency to treat now and why maintenance is important based on LEQEMBI data that we have obtained to date.

我想根據我們迄今為止獲得的 LEQEMBI 數據，簡要回顧為什麼現在需要緊急治療以及為什麼維護很重要。

First, the CLARITY AD study is unique in that it did not exclude patients based upon tau brain pathology.

首先，CLARITY AD 研究的獨特之處在於它沒有根據 tau 腦部病理排除患者。

Therefore, we have placebo-controlled clinical trial data across the full early Alzheimer's disease population, including individuals with no and low tau, which represents the earlier stages of AD. In this population, 76% of patients showed no decline and 60% showed clinical improvement at 18 months as assessed by CDR sum of boxes.

因此，我們擁有針對整個早期阿茲海默症族群的安慰劑對照臨床試驗數據，包括沒有 tau 或 tau 水平較低的個體，這代表了阿茲海默症的早期階段。在該族群中，根據 CDR 總和框架評估，76% 的患者沒有表現出衰退，60% 的患者在 18 個月時表現出臨床改善。

What this means is that in over three-fourths of early AD patients, their disease was stabilized and more than half the patients showed improved symptoms when treated with LEQEMBI.

這意味著超過四分之三的早期 AD 患者在接受 LEQEMBI 治療後病情穩定，超過一半的患者症狀得到改善。

The reason why this is important is that this data suggests that patients treated early in their disease can see a profound benefit, which underscores the importance of initiating treatment early.

這之所以很重要，是因為這些數據表明，早期治療的患者可以獲得巨大的益處，這強調了早期開始治療的重要性。

Furthermore, this data also supports the potential of our ongoing presymptomatic AHEAD 3-45 trial.

此外，這些數據也支持我們正在進行的症狀前 AHEAD 3-45 試驗的潛力。

And now that I've shown you why early treatment initiation is important, let me remind you why the new maintenance IV approval is also very critical.

現在我已經向您說明了為什麼早期開始治療很重要，讓我提醒您為什麼新的維持性靜脈注射批准也非常關鍵。

And that is because data shows that Alzheimer's does not stop after plaque removal.

這是因為數據顯示，阿茲海默症不會在清除斑塊後停止。

Importantly, prior data from the LEQEMBI Phase II study and its open-label extension show that discontinuation of treatment is associated with re-accumulation of Alzheimer's biomarkers, including amyloid blocks and importantly a reversion back to the placebo rate of clinical decline.

重要的是，LEQEMBI 第二階段研究及其開放標籤擴展的先前數據表明，停止治療與阿茲海默症生物標記的重新積累有關，包括澱粉樣蛋白阻滯，重要的是恢復到安慰劑組的臨床衰退率。

With its differentiated mechanism of action, we believe LEQEMBI is uniquely positioned as it is the only disease-modifying therapy in Alzheimer's today to show additional benefit with continued treatment after plaque reduction.

憑藉其差異化的作用機制，我們相信 LEQEMBI 具有獨特的優勢，因為它是當今阿茲海默症中唯一一種在減少斑塊後繼續治療可顯示出額外益處的疾病改良療法。

As you can see from this slide, the three-year data from the CLARITY AD study and its open-label extension support the potential for long-term benefit to patients by showing that continued LEQEMBI treatment resulted in a doubling of the clinical benefit observed at 18 months as compared to a matched natural history cohort.

從這張投影片中您可以看到，CLARITY AD 研究及其開放標籤擴展的三年數據支持了患者長期受益的潛力，表明與匹配的自然史隊列相比，持續的 LEQEMBI 治療可使 18 個月時觀察到的臨床益處翻倍。

With these findings in mind, we are working with Eisai to deliver additional options for patients with the aim of maximizing both the convenience and the clinical benefit of LEQEMBI.

考慮到這些發現，我們正在與 Eisai 合作，為患者提供更多選擇，旨在最大限度地提高 LEQEMBI 的便利性和臨床益處。

This includes a subcutaneous formulation with the potential for at-home administration to further add to patient optionality and convenience.

其中包括一種皮下製劑，可在家中給藥，進一步增加患者的選擇性和便利性。

For subcutaneous maintenance dosing, we now have a PDUFA date of August 2025.

對於皮下維持劑量，我們現在的 PDUFA 日期是 2025 年 8 月。

Next year, in 2026, we aim to introduce subcutaneous dosing for treatment initiation, which we believe will allow even more patients to get started on therapy.

明年，也就是 2026 年，我們的目標是引入皮下給藥來開始治療，我們相信這將使更多的患者能夠開始接受治療。

And building upon the encouraging results we obtained in the no or low tau population in Clarity AD, we continue to advance evaluating the AHEAD 3-45, evaluating LEQEMBI individuals who have amyloid plaque pathology in the brain, but before the onset of symptoms, which has the potential to further expand the use of LEQEMBI.

基於我們在 Clarity AD 中在無 tau 或低 tau 人群中獲得的令人鼓舞的結果，我們繼續推進對 AHEAD 3-45 的評估，評估腦部有澱粉樣斑塊病理但在症狀出現之前的 LEQEMBI 個體，這有可能進一步擴大 LEQEMBI 的使用範圍。

Turning now to the pipeline.

現在轉向管道。

We have previously discussed our efforts to augment our pipeline with the objective of rebalancing the risk profile and investing to win in key areas of expected future growth.

我們之前曾討論過擴大產品線的努力，目的是重新平衡風險狀況並投資於預期未來成長的關鍵領域。

As a result, we have focused our development efforts on a smaller set of clinical stage programs that we believe are high conviction and well positioned to deliver a regular cadence of pivotal readouts and potential launches.

因此，我們將開發工作重點放在一小部分臨床階段項目上，我們認為這些項目具有很高的可信度，並且能夠定期發布關鍵讀數和潛在的發布。

This includes key late-stage programs that have the potential, as you see on this slide, to deliver innovation to benefit patients across Alzheimer's and immunology.

正如您在這張投影片上看到的，這包括一些關鍵的後期項目，這些項目有潛力帶來創新，使阿茲海默症和免疫學患者受益。

We will continue to remain disciplined in our approach as we continue to assess inflection points for our internal development pipeline but also as we evaluate potential external innovation opportunities that we believe can help support Biogen's goal of sustainable growth.

我們將繼續嚴謹地評估我們內部開發管道的轉折點，同時也評估我們認為可以幫助支持 Biogen 實現永續成長目標的潛在外部創新機會。

With that, I would now like to hand the call over to Mike for a financial update.

說完這些，我現在想把電話交給麥克來報告一下財務最新情況。

Thank you, Priya.

謝謝你，普里婭。

Good morning to everyone.

大家早安。

I'd like to begin by providing some highlights from the reported results.

首先，我想介紹一下報告結果中的一些亮點。

Total revenue for the quarter was $2.5 billion, which represents 3% growth from the fourth quarter of 2023.

本季總營收為 25 億美元，較 2023 年第四季成長 3%。

Fourth-quarter non-GAAP diluted EPS was $3.44 and that's 17% higher than the fourth quarter of 2023.

第四季非 GAAP 稀釋每股收益為 3.44 美元，比 2023 年第四季高出 17%。

For the full year of 2024, total revenue of $9.7 billion represents a decline of 2% from 2023, consistent with our most recent guidance of a low single-digit decline.

2024 年全年總收入為 97 億美元，較 2023 年下降 2%，與我們最近預測的低個位數降幅一致。

And full-year 2024 non-GAAP diluted EPS was $16.47 and that's 12% higher than the full-year 2023, also consistent with our most recent guidance range of $16.10 to $16.60.

2024 年全年非 GAAP 稀釋每股收益為 16.47 美元，比 2023 年全年高出 12%，也與我們最近的 16.10 美元至 16.60 美元的指導範圍一致。

EPS growth and operating income expansion in both the fourth quarter and full year was supported by our Fit for Growth and R&D prioritization initiatives.

我們的「適應成長」和「研發優先」措施推動了第四季度和全年每股收益和營業收入的擴大。

We are pleased that this performance allowed us to generate $722 million of free cash flow in the quarter, which brought us to $2.7 billion for the full year and that's an improvement of $1.4 billion from $1.3 billion generated in 2023.

我們很高興，這一業績使我們在本季度產生了 7.22 億美元的自由現金流，這使我們全年的自由現金流達到 27 億美元，比 2023 年的 13 億美元增加了 14 億美元。

Now I'll turn to a few comments on revenue and commercial dynamics from the fourth quarter.

現在我將就第四季的營收和商業動態談幾點評論。

Our MS product revenue declined roughly 8% at actual currency and 9% at constant currency as compared to the fourth quarter of 2023.

與 2023 年第四季相比，我們的 MS 產品收入以實際貨幣計算下降約 8%，以固定匯率計算下降約 9%。

And that was driven primarily by competition in the space, partially offset by some seasonal channel dynamics.

這主要是由該領域的競爭所驅動，但部分被一些季節性通路動態所抵消。

Interferons continued to be impacted by competition as patients transition to higher efficacy therapies and TECFIDERA continued to be impacted by generic competition globally.

隨著患者轉向更有效率的治療方法，幹擾素繼續受到競爭的影響，而 TECFIDERA 繼續受到全球仿製藥競爭的影響。

TYSABRI has seen some impacts from a biosimilar entrant in Europe.

TYSABRI 已經感受到了來自歐洲生物相似藥廠商的一些影響。

And although a biosimilar has not yet launched in the US, we continue to see competition increasing in the high-efficacy class. [Plumerity] saw an increase in demand in the quarter and also benefited from some seasonal channel dynamics.

儘管生物相似藥尚未在美國上市，但我們仍然看到高效藥物領域的競爭日益激烈。 [Plumerity] 本季需求增加，同時也受惠於一些季節性通路動態。

Next, our rare disease franchise produced revenue of $535 million in the fourth quarter and that represented a growth of 13% at actual currency and 15% at constant currency from the fourth quarter of 2023.

其次，我們的罕見疾病特許經營權在第四季度實現了 5.35 億美元的收入，與 2023 年第四季度相比，按實際貨幣計算增長了 13%，按固定匯率計算增長了 15%。

Global SKYCLARYS revenue in the fourth quarter was $102 million, an increase of 83% versus the fourth quarter of 2023 with nearly double the number of patients on therapy.

SKYCLARYS 第四季全球營收為 1.02 億美元，較 2023 年第四季成長 83%，接受治療的患者數量幾乎增加了一倍。

US SKYCLARYS revenue in the fourth quarter was $71 million.

美國SKYCLARYS第四季營收為7,100萬美元。

We continued to add patients in the quarter, but revenue was sequentially impacted by an inventory build in the third quarter that was drawn down in the fourth quarter as well as some Medicare discount dynamics.

我們在本季繼續增加患者，但收入受到了第三季庫存增加（第四季度庫存減少）以及一些醫療保險折扣動態的影響。

Global SPINRAZA revenue of $421 million in the fourth quarter grew 2% year over year, including growth in the US, up 6% year over year.

SPINRAZA第四季全球營收為4.21億美元，年增2%，其中美國市場成長6%。

We are encouraged by the performance here and look forward to a potential future launch of the high-dose option.

我們對此處的表現感到鼓舞，並期待未來可能推出高劑量選項。

ZURZUVAE delivered approximately $23 million of revenue in the quarter, and that was driven by an increase in demand, partially offset by channel dynamics.

ZURZUVAE 本季實現了約 2,300 萬美元的收入，這主要得益於需求的成長，但部分抵消了通路動態的影響。

And we again saw steady sequential growth for LEQEMBI with fourth-quarter global in-market sales booked by Eisai of approximately $87 million and that's up approximately 30% sequentially from the third quarter of 2024.

我們再次看到 LEQEMBI 實現穩定的連續成長，衛材第四季全球市場銷售額約為 8,700 萬美元，比 2024 年第三季環比成長約 30%。

LEQEMBI fourth-quarter end market sales in the US were $50 million and that's up roughly 28% sequentially from the third quarter of 2024.

LEQEMBI 第四季在美國終端市場銷售額為 5,000 萬美元，較上季 2024 年第三季成長約 28%。

I'll now turn to a few comments on dynamics from a few key expense lines.

現在，我將針對幾項關鍵支出的動態發表幾點評論。

Non-GAAP cost of sales as a percentage of revenue improved 300 basis points in the fourth quarter as compared to the fourth quarter of 2023, and that was driven primarily by lower idle capacity charges.

與 2023 年第四季相比，第四季非 GAAP 銷售成本佔收入的百分比提高了 300 個基點，這主要得益於閒置容量費用的降低。

Fourth-quarter non-GAAP core operating expense or R&D plus SG&A expense increased 4% year over year as the benefits from our R&D prioritization and Fit for Growth initiatives allowed us to mostly absorb incremental spend associated with our launches.

第四季非公認會計準則核心營運費用或研發加銷售、一般及行政費用年增 4%，因為我們的研發優先順序和「適合成長」計畫帶來的好處使我們能夠主要吸收與產品發布相關的增量支出。

Non-GAAP other expense was $72 million in the quarter, and that was driven primarily by net interest expense.

本季度非公認會計準則其他支出為 7,200 萬美元，主要由於淨利息支出。

Non-GAAP diluted EPS was $3.44 in the fourth quarter, representing growth of 17% versus the fourth quarter of 2023.

第四季非公認會計準則稀釋每股收益為 3.44 美元，較 2023 年第四季成長 17%。

Now a brief update on our balance sheet.

現在簡單更新一下我們的資產負債表。

We generated $2.7 billion of free cash flow in 2024 due to strong operating income.

由於強勁的營業收入，我們在 2024 年創造了 27 億美元的自由現金流。

Please note that the timing of certain cash tax payments in 2024 also benefited free cash flow.

請注意，2024 年某些現金稅支付的時間也有利於自由現金流。

We ended 2024 with $2.4 billion of cash and roughly $3.9 billion of net debt and continue to believe that our balance sheet remains strong and allows us to continue to invest in both internal and external growth opportunities.

截至 2024 年，我們的現金餘額為 24 億美元，淨債務約為 39 億美元，我們仍然相信我們的資產負債表仍然強勁，並使我們能夠繼續投資於內部和外部成長機會。

Turning now to our full-year 2025 guidance ranges and assumptions.

現在來談談我們的 2025 年全年指導範圍和假設。

We expect full-year 2025 non-GAAP diluted earnings per share of between $15.25 and $16.25. This guidance range, which is based upon FX rates on February 7, 2025, includes a $0.35 EPS headwind from foreign exchange when compared to average exchange rates in 2024.

我們預計 2025 年全年非 GAAP 攤薄每股收益在 15.25 美元至 16.25 美元之間。該指引範圍基於 2025 年 2 月 7 日的外匯匯率，與 2024 年的平均匯率相比，外匯帶來的每股盈餘阻力為 0.35 美元。

Total revenue for 2025 is expected to decline by a mid-single-digit percentage.

預計 2025 年總收入將下降中位數個位數百分比。

This is driven primarily by an increased decline in our MS business as compared to 2024.

這主要是因為與 2024 年相比，我們的 MS 業務下滑幅度加大。

The pressure on our MS business is expected to be driven by potential biosimilar entry for TYSABRI in the US this year and potential generic entry for TECFIDERA in certain European markets.

預計我們 MS 業務面臨的壓力將來自今年 TYSABRI 生物相似藥可能進入美國市場以及 TECFIDERA 仿製藥可能進入某些歐洲市場。

We expect this decline to be partially offset by continued strong and increasing revenue growth from our new product launches.

我們預計，新產品發布帶來的持續強勁且不斷增長的收入將部分抵消這一下降。

Please note this revenue range also includes a roughly 1% headwind from foreign exchange.

請注意，該收入範圍還包括約 1% 的外匯逆風。

In 2025, we expect an impact from Medicare Part D redesign at the total company level to be limited approximately $50 million to $100 million.

到 2025 年，我們預計 Medicare Part D 重新設計對整個公司層面的影響將限制在約 5,000 萬至 1 億美元之間。

We expect approximately one-third of this impact to be related to SKYCLARYS with the remainder coming from MS.

我們預計約三分之一的影響與 SKYCLARYS 有關，其餘影響則來自 MS。

On operating expenses, we remain on track to deliver the $1 billion of gross and $800 million of net savings from our Fit for Growth initiative by the end of this year.

在營運費用方面，我們仍有望在今年年底前透過「適合成長」計畫實現 10 億美元的總節約和 8 億美元的淨節約。

With this in mind, we expect full-year 2025 combined non-GAAP R&D and SG&A expense to total approximately $3.9 billion.

考慮到這一點，我們預計 2025 年全年非 GAAP 研發和銷售、一般及行政費用總計約為 39 億美元。

And as it will take time for the savings to crystallize, we expect to see higher OpEx in the beginning of the year.

由於節省的成本需要時間才能反映出來，我們預計年初的營運支出將會更高。

We expect non-GAAP operating margin percentage to remain relatively flat in 2025 as compared to 2024.

我們預計，2025 年非 GAAP 營業利潤率百分比與 2024 年相比將保持相對穩定。

And on the nonoperating side of expenses, I would highlight the components of our non-GAAP other income and expense line.

在非營業費用方面，我想重點介紹非公認會計準則其他收入和支出的組成部分。

This line includes interest expense on our debt and some other expenses, partially offset by interest income on our cash balances.

此行包括我們的債務利息支出和一些其他支出，部分由我們的現金餘額的利息收入抵銷。

For full-year 2025, we expect other income and expense to be a net expense of approximately $180 million to $220 million.

就 2025 年全年而言，我們預計其他收入和支出的淨支出約為 1.8 億美元至 2.2 億美元。

And finally, some additional considerations as you think about your models.

最後，當您思考您的模型時，還需要考慮一些其他因素。

As has been the case in previous years, we expect the first quarter to be pressured due to seasonality, driven by higher discounts and allowances as well as channel dynamics in the US, and that will mostly impact our MS business.

與往年一樣，我們預計第一季將受到季節性壓力，受折扣和配額增加以及美國通路動態的影響，這將對我們的 MS 業務產生最大影響。

I would also note with regard to [FAMPYRA] that we terminated the license and collaboration agreement effective January 1, 2025.

我還要指出的是，關於 [FAMPYRA]，我們已於 2025 年 1 月 1 日起終止許可和合作協議。

And as I just mentioned, our current year guidance takes account of the stronger dollar today compared with the same time last year.

正如我剛才提到的，我們今年的指引考慮到了目前美元較去年同期走強的趨勢。

For modeling purposes, each cent change in the euro versus the US dollar impacts revenue by approximately $15 million.

出於建模目的，歐元兌美元每變化一分錢就會對收入產生約 1500 萬美元的影響。

I would also refer you to the current slide as well as our press release for other important guidance assumptions.

我還請您參閱當前幻燈片以及我們的新聞稿，以了解其他重要的指導假設。

And in closing, we welcome Robin Kramer, as Biogen's CFO, following my retirement later this quarter.

最後，我們歡迎 Robin Kramer 擔任 Biogen 的財務官，我將在本季稍後退休。

This orderly transition plan has been in process for some time now, and I have full confidence that Robin will be a great CFO.

這個有序的過渡計劃已經進行了一段時間，我完全相信羅賓會成為一名出色的財務長。

I'm excited about Biogen's future and will remain a supporter and shareholder of Biogen in the years to come.

我對 Biogen 的未來感到興奮，並將在未來幾年繼續成為 Biogen 的支持者和股東。

And with that, we will now open the call up for questions.

現在，我們將開始回答問題。

Thanks, Mike.

謝謝，麥克。

Jennifer, can we go to the first question, please?

詹妮弗，我們可以開始第一個問題嗎？

(Operator Instructions) Salveen Richter, Goldman Sachs.

（操作員指示） Salveen Richter，高盛。

What is your latest thinking on the capacity preference and potential time lines for external BD?

您對外部 BD 的容量偏好和潛在時間表的最新想法是什麼？

And in terms of your growth outlook, just help us understand the balance between the existing pipeline and the assets you could bring in?

就您的成長前景而言，您能幫助我們了解現有管道和您可以引入的資產之間的平衡嗎？

Thanks, Salveen.

謝謝，薩爾文。

I mean, I think we'll get Mike to give you an update on capacity.

我的意思是，我想我們會讓麥克向您報告容量的最新情況。

As I said, we are very excited about the pipeline that we have.

正如我所說，我們對我們擁有的管道感到非常興奮。

But I think one of the things that we'd like to do is continue to reinforce that pipeline.

但我認為我們想做的事情之一是繼續加強這個管道。

Over the years, I've come to the conclusion that you can never have enough pipeline.

多年來，我得出的結論是，管道永遠不會太多。

First element is we've done a major restructuring of research because I think as companies in our industry, it's very expensive to bring in late-stage assets.

首先，我們對研究進行了重大重組，因為我認為，對於我們這個行業中的公司來說，引入後期資產的成本非常高。

And we would like to have research be our primary source of innovation, obviously internally but also externally.

我們希望研究成為我們創新的主要來源，顯然不僅是內部創新，也是外部創新。

And so I think we have completely restructured research to create the financial capacity as well as the talent capacity to do more collaborations and bring assets in, particularly pre GLP tox.

因此，我認為我們已經完全重組了研究，以創造財務能力和人才能力，以進行更多合作並引入資產，特別是 GLP 前毒性。

Beyond that, we are looking at virtually every phase, the early phase development.

除此之外，我們幾乎正在關注每個階段，也就是早期發展階段。

Right now, I would say, Priya would probably agree with me, that our early-stage development pipeline is still relatively thin.

現在，我想說，Priya 可能會同意我的觀點，即我們的早期開發管道仍然相對較薄弱。

But even if we can find things in Phase III, if it's got a really solid Phase II, I'm not big on taking a lot of risk on Phase III clinical trials because that gets expensive.

但即使我們能夠在第三階段找到一些東西，如果它有一個非常穩固的第二階段，我也不太願意在第三階段臨床試驗中承擔太多風險，因為那樣成本會很高。

And in terms of acquisitions, we have been migrating in new areas such as immunology and rare diseases.

在收購方面，我們一直在向免疫學和罕見疾病等新領域邁進。

And if we can find acquisitions that can bolster our positions in that, we will do so.

如果我們可以找到能夠鞏固我們地位的收購，我們就會這樣做。

We don't have a particular size that we're looking for.

我們沒有想要的特定尺寸。

It could be late stage development.

這可能是後期開發。

It could be early stage commercial.

它可能還處於早期商業階段。

The one thing it has to do is make financial sense.

它必須做的一件事就是具有財務意義。

I think where we are as a company, we don't need to be taking a huge amount of risk on acquisitions.

我認為，作為一家公司，我們不需要在收購上承擔巨大的風險。

That said, we are always looking.

話雖如此，我們一直在尋找。

We always have about at least 15 to 20 different projects that we're looking at at any one time.

我們總是同時專注於至少 15 至 20 個不同的項目。

But as you know, you kind of have to look at 100 things before you find something that is of interest.

但如你所知，你必須研究 100 件事物才能找到感興趣的東西。

And Mike, maybe you want to talk about capacity?

麥克，也許你想談談容量？

Yes.

是的。

And Salveen, on capacity, the balance sheet remains in excellent shape.

就產能而言，Salveen 的資產負債表仍保持良好的狀態。

As we mentioned in the prepared remarks, we ended the year with $2.4 billion of cash on hand.

正如我們在準備好的評論中提到的那樣，到今年年底，我們的現金餘額為 24 億美元。

The EBITDA run rate is north of $3 billion a year.

EBITDA 運作率每年超過 30 億美元。

So with $6.3 billion of gross debt and $3.9 billion of net debt, you're in the ZIP code of maybe 2 turns gross and 1.5 turns net.

因此，在總債務為 63 億美元、淨債務為 39 億美元的情況下，您所在的郵遞區號區域的總債務可能為 2 倍，淨債務為 1.5 倍。

And we were very pleased with the free cash flow results this year -- or last year, I should say, 2024, $2.7 billion.

我們對今年（或去年，也就是 2024 年）的自由現金流結果感到非常滿意，為 27 億美元。

So that cash balance will continue to grow.

因此現金餘額將繼續增長。

So when you look at the modest amount of leverage, the $2.4 billion of cash on hand and the growing free cash flow, the balance sheet is in an excellent position.

因此，當您看到適度的槓桿、24 億美元的庫存現金以及不斷增長的自由現金流時，您會發現資產負債表處於極佳的狀態。

As Chris said, the plan will be to stay very disciplined and only do things that make good financial sense, but we've got significant capacity to do a series of smaller things or perhaps a larger thing if it does make good financial sense.

正如克里斯所說，我們的計劃是保持高度自律，只做那些具有良好財務意義的事情，但我們也有足夠的能力去做一系列較小的事情，或者如果具有良好的財務意義的話，去做一件較大的事情。

Michael Yee, Jefferies.

傑富瑞 (Jefferies) 的麥可餘 (Michael Yee)。

Priya, you mentioned on the LEQEMBI slide that one of the important developments is the potential for blood-based diagnostics.

Priya，您在 LEQEMBI 幻燈片上提到，其中一項重要發展是基於血液的診斷的潛力。

And my understanding is that that's coming this year.

據我了解，這將在今年實現。

Can you walk through how important that is in terms of any bottlenecks and specifically whether that totally would be able to replace PET or how that actually works since diagnostics are a little bit complicated?

您能否說明一下這在瓶頸方面的重要性，特別是它是否完全能夠取代 PET，或者它實際上是如何運作的，因為診斷有點複雜？

Yes.

是的。

Thanks, Mike.

謝謝，麥克。

So overall, I think that accurate diagnosis of Alzheimer's disease and confirmation of amyloid remains very important.

所以總的來說，我認為準確診斷阿茲海默症和確認澱粉樣蛋白仍然非常重要。

And it is the entry point for the kind of care pathway here.

這是此類護理途徑的切入點。

So it's important.

所以這很重要。

I think with the advent of the anti-amyloid therapy, we've seen amazing momentum there.

我認為隨著抗澱粉樣蛋白療法的出現，我們已經看到了驚人的發展勢頭。

And as Chris mentioned, we have tests available today that are at triage sort of level.

正如克里斯所提到的，我們今天提供的測試已經達到了分類等級。

The question here is what is going to be the availability in the near term for an in vitro diagnostic approved by the FDA that can be used widely and can also be reimbursed and give physicians and neurologists confidence that they can actually trust that outcome and that result versus a PET.

這裡的問題是，短期內是否有一種體外診斷方法能夠獲得 FDA 批准，並且可以廣泛使用，還可以報銷，並且讓醫生和神經病學家有信心他們可以真正信任該結果，而不是 PET。

And we think that this is likely going to happen in the near term.

我們認為這很可能在短期內發生。

FujireBio is already filed.

FujireBio 已提交申請。

We know there are a couple of others like C2N and Roche that are sort of working on these IVDs or in vitro diagnostics.

我們知道還有其他幾家公司，例如 C2N 和羅氏，也致力於 IVD 或體外診斷的研究。

And one was already filed -- FujireBio filed last year.

其中一家已經提交了申請書——FujireBio 去年提交了申請。

We believe that usually the time frame is about six months.

我們認為通常時間範圍約為六個月。

I think the next stage will be generating data so that payers and others are confident that it can adequately represent the Medicare population, which tends to be the broader population.

我認為下一階段將是產生數據，以便付款人和其他人相信它能夠充分代表醫療保險人群，而這往往是更廣泛的人群。

So I think concordance is important as is reimbursement.

所以我認為一致性和報銷同樣重要。

But we think this is moving really fast, and we think we'll see quite a few milestones occur in the near term.

但我們認為這一進程確實很快，而且我們認為我們將在短期內看到不少里程碑事件。

Tim Anderson, Bank of America.

美國銀行的蒂姆·安德森。

On your spend guidance, you're saying $3.9 billion combined R&D and SG&A, which is about $200 million lower than consensus.

在您的支出指引中，您說研發和銷售、一般及行政開支總計為 39 億美元，比普遍預期低約 2 億美元。

Revenues are also a little bit lower than consensus so it offsets each other.

收入也比普遍預期略低，因此相互抵消。

My question is how much does the Royalty Pharma deal take out of the R&D line in 2025, specifically?

我的問題是，到 2025 年，Royalty Pharma 交易將從研發線中拿出多少錢？

I know it's $250 million in aggregate that they'll fund, but what's that relief to 2025 R&D?

我知道他們總共提供 2.5 億美元的資金，但這對 2025 年的研發有什麼幫助呢？

And then on Royalty Pharma, can we expect Biogen to do more of these off-balance sheet types of transactions with pipeline programs over the next one to two years?

那麼就 Royalty Pharma 而言，我們是否可以預期 Biogen 在未來一到兩年內會透過管道項目進行更多此類表外交易？

So Tim, Mike speaking.

提姆，我是麥克。

On the Royalty Pharma transaction, our current expectation is that the $200 million that we would receive in 2025 from Royalty Pharma would be accounted for as a reduction to R&D expense.

關於 Royalty Pharma 交易，我們目前預計，2025 年從 Royalty Pharma 獲得的 2 億美元將作為研發費用的減少。

So that would be a dollar-for-dollar reduction that's in the mix of our guidance.

所以這將是一美元一美元的減少，符合我們的指導範圍。

Well, just in terms of other deals, the remuneration to those providing the financing is usually through royalties.

嗯，就其他交易而言，對提供融資的人的報酬通常是透過特許權使用費。

And it's not easy to make work for every product.

但要讓每種產品發揮作用並不容易。

So I think at the moment, we look at this as a one-off transaction.

因此我認為目前我們將其視為一次性交易。

But it is a useful model to take risk off the table and be able to spread the investment across more assets.

但這是一個有用的模型，可以消除風險並將投資分散到更多資產。

I mean, it's essentially a way of getting more shots on goal.

我的意思是，這本質上是一種獲得更多射門機會的方法。

Brian Abrahams, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Brian Abrahams。

On SKYCLARYS, can you elaborate a little bit more on the dynamics you're seeing in the US?

關於 SKYCLARYS，您能否進一步詳細說明您在美國看到的動態？

Are there ways to accelerate patient identification to meaningfully grow revenue there?

有什麼方法可以加速患者識別，從而顯著增加收入？

Should we be expecting this to more be an ex US international growth product?

我們是否應該期待它更多地成為一種非美國國際成長產品？

And how are the hurdles in terms of reimbursement outside the US?

那麼在美國境外報銷方面的障礙有哪些呢？

So in the US, I think there have been already a number of creative approaches.

因此我認為在美國已經出現了許多富有創意的方法。

One is using AI and looking across social media to be able to identify where patients are.

一是使用人工智慧並查看社交媒體以確定患者的位置。

As I said before, there's quite a large number of potential prescribers you could go to.

正如我之前所說，你可以諮詢很多潛在的處方醫生。

So the question is how do you zero that down to a geography and a type of physician that makes the visit efficient.

所以問題是如何將其歸結為地理位置和醫生類型，以使就診更有效率。

And so we say we've used the AI.

所以我們說我們使用了人工智慧。

Obviously, whenever you develop a treatment for a disease, there's a greater interest in diagnosing it.

顯然，每當你開發出疾病的治療方法時，人們對診斷疾病的興趣就會更大。

And so I think one of the things that we're seeing is a much greater use of genetic testing.

所以我認為我們看到的事情之一就是基因檢測的使用越來越廣泛。

Genetic testing does have a cost and physicians have not always been interested in using it if it wasn't going to lead to a treatment.

基因檢測確實需要花費一些成本，而且如果不能起到治療作用的話，醫生並不總是願意使用它。

But now that SKYCLARYS is there, we are seeing that increased utilization.

但現在有了 SKYCLARYS，我們看到利用率提高。

The final thing is using multi omnichannel marketing to be able to reach physicians just to educate them about what is Friedreich's ataxia.

最後一件事是使用多全通路行銷來接觸醫生，以便向他們介紹什麼是弗里德賴希共濟失調。

There are also multiple ataxias out there.

還有多種共濟失調症。

And so that's where the genetic testing can become important.

所以這就是基因檢測變得重要的原因。

But when you listen to the patient journeys, it can take often three, four years before a patient gets a definitive diagnosis.

但當你傾聽患者的病情變化時，你會發現，通常需要三、四年的時間，患者才能得到明確的診斷。

A lot of particularly younger people are just kind of thought to be clumsy for a period of time and then progressively lose mobility.

許多年輕人在一段時間內都會被認為行動笨拙，然後逐漸喪失行動能力。

And it takes a while because there are a lot of physicians who've never even heard of, as I said, Friedrich's ataxia, and so that's why the education is needed.

這需要一段時間，因為很多醫生甚至從未聽說過，正如我所說的，弗里德里希共濟失調，所以這就是為什麼需要教育。

I would say today with the technology we have, we have a lot of tools that we didn't have even 15 years ago.

我想說，今天憑藉我們現有的技術，我們擁有很多 15 年前所沒有的工具。

But it is still finding patient by patient.

但仍在不斷尋找每一個患者。

We look at how many patients we found every week.

我們查看每週發現了多少名患者。

And then the reimbursement isn't really an issue in the US.

那麼報銷在美國其實不是問題。

There are hurdles to it.

但其中仍存在一些障礙。

This is where Biogen is particularly good.

這正是 Biogen 尤其擅長的地方。

We have a very adept group that can help patients navigate the reimbursement system.

我們擁有一支非常熟練的團隊，可以幫助患者了解報銷系統。

In Europe, I don't think we're necessarily seeing any -- going to find any issues of reimbursement.

在歐洲，我認為我們不一定會發現任何報銷問題。

It's mostly getting through the whole process, presenting the cost-effectiveness data, but we are very encouraged by the uptake.

它主要是貫穿整個過程，呈現成本效益數據，但我們對這種採用感到非常鼓舞。

And once you have uptake, then that's a good demonstration of the value of the medicine when it comes to discussing things with reimbursing countries.

一旦獲得了認可，那麼在與償付國進行討論時，這將很好地體現出該藥品的價值。

So it will be progressive.

因此它將是進步的。

I think there are 10 countries today in Europe, which reimburse.

我認為目前歐洲有 10 個國家實施償還政策。

And every quarter, we'll be adding more countries.

每個季度我們都會增加更多的國家。

And the same will be true ex Europe and in Latin America, for example.

同樣的情況也將發生在歐洲和拉丁美洲以外地區。

Marc Goodman, Leerink Partners.

馬克古德曼（Marc Goodman），Leerink Partners。

Could you give us a little more flavor on what's happening with SPINRAZA in the US?

您能否向我們詳細介紹 SPINRAZA 在美國的發展？

And the US dynamics and how much inventory is mattering, what's happening with pricing?

那麼美國的動態和庫存量有多重要，定價情況如何？

Just a little more color there.

那裡顏色稍微豐富了一點。

Mike, take the inventory question.

麥克，回答一下庫存問題。

SPINRAZA, so this is a very competitive market with a very limited number of patients.

SPINRAZA，因此這是一個競爭非常激烈的市場，患者數量非常有限。

So you've got a gene therapy, an oral therapy, and an intrathecal therapy, all competing for a relatively small patient number.

因此，有基因療法、口服療法和鞘內療法，所有這些療法都在爭奪相對較少的患者數量。

There are actually quite a number of patients who have not been diagnosed or treated.

實際上有相當多的病人尚未得到診斷或治療。

So we tend to be in younger patients, but there is actually a much larger adult patient population.

因此，我們傾向於針對較年輕的患者，但實際上成年患者群體要大得多。

And getting at those is a lot like the same process that I just described for Friedreich's ataxia.

獲得這些的過程與我剛才描述的弗里德賴希共濟失調的過程非常相似。

So we are doing that.

所以我們正這麼做。

So the interesting thing is how do you compete in the market like that.

所以有趣的是你如何在這樣的市場上競爭。

And we've all grown up in this business and we say, okay, one pill a day beats two pills a day; a pill beats an injection.

我們都在這個行業中長大，我們說，好吧，每天吃一粒藥總比每天吃兩粒藥好；吃藥勝過注射。

But the actual reality is, in a lot of these devastating diseases, efficacy that matters.

但實際情況是，對於許多毀滅性疾病來說，療效才是最重要的。

And that's really the story of SPINRAZA.

這就是 SPINRAZA 的真實故事。

The high dose, I think, will be important because you can get to the therapeutic levels of drug that you need much faster.

我認為高劑量很重要，因為你可以更快達到所需的治療藥物水平。

And in a neurodegenerative disease, that's extremely important.

對於神經退化性疾病來說，這一點極為重要。

So we will be able to cut the number of loading doses, if you like, from four to two, and then you go to three injections per year.

因此，如果您願意，我們可以將負荷劑量的次數從四次減少到兩次，然後每年註射三次。

One of the things that I think will be important is we are developing a device that hopefully will hit the market about, I think, 2026, Priya.

我認為重要的一件事是我們正在開發一種設備，希望能夠在 2026 年左右上市，Priya。

And it's a port that you can insert under the skin pretty much anywhere on the body, but certainly around the abdomen as an example, and has tiny catheters that lead to the spinal column.

它是一個可以插入到身體任何部位皮下的端口，但肯定是腹部周圍的例子，並且有微小的導管通向脊柱。

And that means that you can actually just do the injection directly under the skin.

這意味著您實際上可以直接在皮下注射。

That has had huge patient positive response, and that could actually make intrathecal injections a whole lot more patient friendly, not just in SMA, but pretty much for all of the intrathecal products that we're developing.

此舉得到了患者的積極回應，實際上可以使鞘內注射更加方便患者，不僅限於 SMA，幾乎適用於我們正在開發的所有鞘內注射產品。

So I think that one will also be a game changer going forward.

所以我認為這也將成為未來的遊戲規則改變者。

And Mike, do you want to talk about the inventory dynamic?

麥克，你想談談庫存動態嗎？

Yes.

是的。

Mark, nothing to call out on inventory.

馬克，庫存方面沒什麼好說的。

We did see some lumpiness in SPINRAZA revenue throughout 2024 due to some shipment timing and so forth outside of the US.

由於美國以外的一些發貨時間等原因，我們確實看到 2024 年 SPINRAZA 的收入出現一些波動。

But the fourth quarter, the global 2% growth and the 6% in the US, nothing material to call out in terms of inventory or channel dynamics.

但第四季度，全球成長 2%，美國成長 6%，在庫存或通路動態方面沒有什麼實質的值得關注的。

Paul Matteis, Stifel.

保羅·馬泰斯（Paul Matteis），Stifel。

Chris, if you take a step back now, you got to be at a point, I would think, with ZURZUVAE, SKYCLARYS, LEQEMBI, to some degree, although maybe the variance of outcomes there is a little bit wider.

克里斯，如果你現在退一步想一想，我想，你一定已經與 ZURZUVAE、SKYCLARYS、LEQEMBI 處於同一水平，儘管那裡的結果差異可能更大一些。

Or at least for the next couple of years, you probably have a pretty good window into the range of outcomes for these products.

或者至少在接下來的幾年裡，您可能會很好地了解這些產品的一系列結果。

So I guess taking a step back, do you feel like you can get back to sustainable revenue growth based on what you have internally and what you have high visibility into?

所以我想退一步來說，您是否覺得您可以根據您內部擁有的資源和您所高度關注的事物恢復可持續的收入增長？

Or how important, I guess, is getting a big upside win from the pipeline or buying growth externally via BD?

或者，我猜，從管道中獲得巨大的上行收益或透過 BD 從外部購買成長有多重要？

Right.

正確的。

Well, we've got about -- if you add in everything, there's probably about $4.5 billion of revenue in MS left and probably about $3 billion of profit.

好吧，如果把所有錢加起來，微軟大概還剩下 45 億美元的收入，大約 30 億美元的利潤。

So that's going to be the headwind over the next 5 to 10 years because actually, some of these products are actually quite sticky with patients because patients do well on these products and tend to stay on them.

因此，這將成為未來 5 到 10 年的阻力，因為實際上，其中一些產品對患者來說實際上相當具有黏性，因為患者對這些產品反應良好並且傾向於繼續使用它們。

So it's a slower decline.

因此下降速度比較慢。

So that's the problem we're solving for.

這就是我們要解決的問題。

When you look at it, the number one product that has the most potential to offset is clearly LEQEMBI.

看看它，最具抵消潛力的頭號產品顯然是 LEQEMBI。

And there, I think we are encouraged by the more recent results, and I think we feel pretty confident that these catalysts could offer the potential to see some acceleration of growth.

我認為，最近的結果令我們感到鼓舞，我們非常有信心，這些催化劑可能帶來加速成長的潛力。

So we do believe that there's a tremendous unmet need in Alzheimer's.

因此我們確實相信，阿茲海默症的治療需求還有很大的未滿足空間。

People forget that this is a fatal disease.

人們忘記了這是一種致命的疾病。

And when you look at the data that Priya showed, if you could get 76% of patients stabilized on this, this is data that I think we really need to do more of in demonstrating the value proposition of LEQEMBI.

當您查看 Priya 展示的數據時，如果您可以讓 76% 的患者病情穩定下來，那麼我認為我們確實需要做更多這樣的數據來證明 LEQEMBI 的價值主張。

So we have a number of different approaches.

因此，我們有許多不同的方法。

We've, I think, had extremely productive discussions with our partner, Eisai, on the commercial approach.

我認為，我們與合作夥伴衛材就商業方法進行了非常有成效的討論。

And there was an awful lot of effort at the start just to explain care pathways and the side effects and the reimbursement.

一開始就花費了大量精力來解釋護理途徑、副作用和報銷。

And I think now we can actually focus a lot more on the value proposition and why treating patients.

我認為現在我們實際上可以更多地關注價值主張以及治療患者的原因。

I think there's a huge opportunity in expanding the prescriber base.

我認為擴大處方人員基礎存在巨大機會。

We have focused on a smaller number just because of the effort involved by the neurologist.

由於神經科醫生付出的努力，我們只關注了較少的數量。

But I think with things like the subcutaneous formulations and the maintenance, we have an opportunity to go broader.

但我認為，透過皮下製劑和維護等方面的改進，我們有機會走得更遠。

There's about 13,000 physicians who are targets, and we have a small fraction of those today we're actually prescribing.

大約有 13,000 名醫生是目標，而我們今天實際開處方的只是其中的一小部分。

So there's a lot there, and SKYCLARYS will continue to grow, as we said.

所以這裡有很多東西，而且正如我們所說的，SKYCLARYS 將繼續發展。

ZURZUVAE is certainly an interesting, I'd call it, kind of a two-base hit in baseball terms in the US.

ZURZUVAE 確實是一種有趣的運動，我稱它為美國棒球術語中的兩壘安打。

Europe will probably be a more limited set of markets that will actually be able to reimburse this product.

歐洲可能只是少數真正能夠報銷該產品費用的市場。

I think we've got a lot that we can be doing.

我認為我們可以做很多事。

I think the real growth story is when you start to see the pipeline coming through, because as the MS portfolio declines and the new products become a bigger part of the equation, then suddenly you add a pipeline product on top of that.

我認為真正的成長故事是當你開始看到管道出現的時候，因為隨著 MS 產品組合的下降和新產品成為方程式中更重要的一部分，然後你突然在其上添加了一個管道產品。

And the nice thing about Biogen is that $1 billion really moves the needle.

而 Biogen 的優點在於，10 億美元確實扮演了推動作用。

So we don't need a lot here to really have a meaningful impact on our growth.

因此，我們不需要做太多的事情就能對我們的成長產生真正的有意義的影響。

And so I think it's a combination of all of the above, Paul.

所以我認為這是以上所有因素的結合，保羅。

We will see an increasing percentage of our business coming from these new products, and the pipeline can only augment that.

我們將看到越來越多的業務來自這些新產品，而產品線只會增強這一比例。

Umer Raffat, Evercore.

烏默·拉法特（Umer Raffat），Evercore。

I want to say thank you to Mike for all your help over time, and welcome to Tim.

我想對 Mike 一直以來的幫助表示感謝，並歡迎 Tim。

I have two questions today, if I may.

如果可以的話，我今天有兩個問題。

First, maybe for Priya.

首先，也許對於 Priya 來說。

Priya, in a scenario where Lilly hits Trailblazer Alzheimer's 3 in preclinical on the progression endpoint, how does that factor into your thinking around how you could accelerate time lines for AHEAD 3-45?

Priya，如果禮來公司在臨床前進展終點上達到 Trailblazer Alzheimer's 3，這對您如何加速 AHEAD 3-45 時間表的思考有何影響？

And also your comfort with the endpoint being used there.

以及您對在那裡使用的端點的舒適度。

And secondly, Chris, maybe a big picture question.

其次，克里斯，這可能是一個大問題。

It seems like where the valuation stands today around $20 billion in market cap relative to the amount paid for Reata as well as the amount of balance sheet available for an additional deal coming up, I guess, market is almost reflecting somewhat of a view that the M&A choices in the last couple of years may not have been what market was expecting, or perhaps the expectations were higher.

相對於為 Reata 支付的金額以及即將進行的額外交易的資產負債表金額，目前的估值似乎約為 200 億美元，我猜，市場幾乎反映出這樣一種觀點，即過去幾年的併購選擇可能不是市場所預期的，或者預期可能更高。

I guess, how do you think about all of that?

我想，您對這一切有什麼看法？

And what learnings are you taking from that into additional capital deployment?

您從中得到了哪些經驗教訓，可以用於額外資本的部署？

Because it will be a very significant move if there were to be a $10 billion deal again.

因為如果再次達成 100 億美元的交易，這將是一個非常重大的舉措。

I can get started.

我可以開始了。

Thanks, Umer.

謝謝，烏默爾。

So I think, overall, we remain excited, as I shared in my prepared remarks about the potential for AHEAD 3-45.

因此我認為，總的來說，我們仍然感到興奮，正如我在準備好的演講中所分享的 AHEAD 3-45 的潛力一樣。

Just a reminder is that we completed enrollment last year.

需要提醒的是，我們去年已經完成招生了。

It's a four-year therapy.

這是一個為期四年的治療。

And so we expect -- and Eisai has recently actually reiterated the outcome expected in 2028.

因此我們預計——衛材最近實際上重申了 2028 年的預期結果。

Now that said, we always retain and we always continue to evaluate optionality for earlier readouts and earlier cuts, and we continue to engage with regulators like the FDA very closely on this, and all of that is progressing well.

話雖如此，我們始終保留並始終繼續評估早期讀數和早期削減的可選性，並且我們將繼續與 FDA 等監管機構就此事保持密切合作，所有這一切進展順利。

So that's kind of the acceleration piece.

這是一種加速度部分。

I think the important piece here is the way we've designed the trial.

我認為這裡最重要的是我們設計試驗的方式。

It is quite specific for amyloid load.

它對澱粉樣蛋白負荷有很強的特異性。

And as you know, it's two sister trials, one with a lower amyloid load that's AHEAD-3; and then 4, 5, which is a higher amyloid load.

如您所知，這是兩項姊妹試驗，一項是澱粉樣蛋白含量較低的試驗，即 AHEAD-3；然後是 4、5，這是更高的澱粉樣蛋白負荷。

Now in the AHEAD 3, we have a biomarker outcome, which is amyloid clearance essentially.

現在在 AHEAD 3 中，我們有一個生物標記結果，本質上是澱粉樣蛋白清除率。

But in the 4, 5, where patients have a higher load of amyloid, we are looking at a very important endpoint that's called the PACC5, which is the preclinical Alzheimer's cognition composite.

但在 4、5 中，患者的澱粉樣蛋白負荷量較高，我們正在研究一個非常重要的終點，稱為 PACC5，即臨床前阿茲海默症認知綜合指標。

This comprises elements of memory, the intelligence test, MMSE, and other components.

這包括記憶、智力測驗、MMSE 和其他組成部分。

And it is supposed to be quite sensitive and specific for preclinical AD. Trailblazer 3 has different outcomes like CDR global score and is also doing a time to event.

並且它對於臨床前 AD 應該具有相當高的敏感性和特異性。 Trailblazer 3 有不同的結果，例如 CDR 全球得分，並且還會安排活動時間。

So I think we'll wait to see more on how that unfolds.

因此我認為我們應該拭目以待，看看事情將如何發展。

But I think we feel very confident about the design of this trial and what it can actually tell us about preventing or slowing down onset of Alzheimer's disease.

但我認為我們對這次試驗的設計以及它實際上如何預防或減緩阿茲海默症的發病非常有信心。

Over to you, Chris.

交給你了，克里斯。

Yes.

是的。

I mean, Umer, look, there's a human factor here, right?

我的意思是，烏梅爾，你看，這裡有人為因素，對吧？

One of the things I have seen over the years is that your interest in doing significant acquisitions is kind of inversely proportional to your level of confidence in what you've already got in your pipeline.

多年來我發現，你對進行重大收購的興趣與你對已有業務的信心程度成反比。

So if you don't think you have a lot in your pipeline, you're more likely to be interested in spending more externally.

因此，如果您認為自己沒有太多儲備，那麼您更有可能在外部投入更多資金。

And whether that's logical or not, it is tended to be where you are.

並且不管這是否合乎邏輯，它都傾向於存在於你所在的地方。

And I have to say coming into Biogen, we tend to go after the hardest problems to solve, where we didn't understand the underlying disease biology, where we didn't really have Phase II data that could really predict where we were in Phase III.

我必須說，來到 Biogen 後，我們傾向於解決最困難的問題，我們不了解潛在的疾病生物學，也沒有可以真正預測我們處於第三階段的 II 期數據。

And at that point, you sort of say, well, if you don't know what you've got, you're more interested in looking at things.

到了那個時候，你就會說，如果你不知道自己得到了什麼，你會更有興趣看看一些東西。

I would say where we are now two years down the road is, I think, Priya with her steely-eye has really taken a lot of the stuff out of our pipeline that either was never going to make it to market; or if it did make it to market, was never going to have much impact.

我想說，兩年後我們的情況是，我認為，Priya 用她堅定的目光確實從我們的管道中剔除了很多原本永遠不會進入市場的東西；或者即使它確實進入了市場，也不會產生太大的影響。

And what we do have, and we've got more data now, gives us a whole lot more confidence.

我們現在擁有的以及更多的數據給了我們更多的信心。

I mean, when you got a dapirolizumab now with a Phase III, I mean, litifilimab has advanced -- the HI-Bio acquisition, we see as pretty transformative for our pipeline because that is exactly what we would like to see more of, is data in Phase II that really gives you a sense of some level of conviction into Phase III, recognizing that there are never any guarantees in R&D.

我的意思是，當你獲得目前處於 III 期的達匹羅珠單抗時，我的意思是，利替利單抗已經取得了進展——HI-Bio 的收購，我們認為對我們的產品線來說具有相當大的變革性，因為這正是我們希望看到的，II 期的數據確實讓你對 III 期有一定程度的信心，認識到研發中永遠沒有任何保證。

So I think where we are is we could continue to do more of the HI-Bio type transactions.

因此我認為我們可以繼續進行更多 HI-Bio 類型的交易。

We actually like the Reata transaction.

我們確實喜歡 Reata 交易。

Maybe the Street had a different view, but I don't think the Street really completely understand how some of these rare diseases really work.

也許華爾街有不同的看法，但我認為華爾街並沒有真正完全了解這些罕見疾病的具體發病機制。

For us, over time, we believe that SKYCLARYS is going to be a significant product.

對我們來說，隨著時間的推移，我們相信 SKYCLARYS 將成為一款重要的產品。

I think it is already a significant product.

我覺得它已經是一個很有意義的產品了。

If we found another Reata where we -- you've got a product that is about to be launched on the market, and you could buy it for a price that generates a return for our shareholders, then we would do it.

如果我們發現另一個領域——您擁有即將推出市場的產品，並且您可以以能為我們的股東帶來回報的價格購買它，那麼我們就會這樣做。

But I think part of the problem is I don't think the people who are selling companies have quite integrated a lot of the pressures that are on this industry.

但我認為問題的一部分在於，我認為出售公司的人還沒有完全整合該行業面臨的許多壓力。

The IRA is a de facto reduction in patent life for our industry, and there's a lot of pricing pressure from around the world.

IRA 事實上縮短了我們行業的專利壽命，而且來自世界各地的定價壓力也很大。

So the total commercial return for any one molecule today is not what it was even five years ago.

因此，今天任何一種分子的總商業回報都不如五年前。

And yet, I don't see really any shift in the premiums being paid or the price being paid.

然而，我並沒有看到支付的保費或支付的價格有任何變化。

And there's always an asymmetry between the products that you know and the products that you're going to buy.

您所了解的產品和您要購買的產品之間總是存在不對稱。

And so I think right now, we will look.

所以我認為現在我們就來看一下。

If we could find another Reata, we would probably do it.

如果我們能找到另一個 Reata，我們可能會這樣做。

We don't particularly want to do one deal that takes all of our cash flow because I think there is an interest in building the pipeline with multiple assets.

我們並不特別想做一筆耗費我們所有現金流的交易，因為我認為人們對建造包含多項資產的管道感興趣。

If we could do more HI-Bios, that's probably a nice sweet spot for us.

如果我們可以做更多的 HI-Bios，這對我們來說可能是個不錯的選擇。

We've kind of concluded that, actually, we can probably manage quite nicely until the pipeline matures even further.

我們實際上已經得出結論，在管道進一步成熟之前，我們或許能夠管理得相當好。

So we don't feel any particular pressure to do things, but I do think it's a job of every leadership person in this business to constantly look outside if we can find other sources of innovation.

因此，我們並沒有感受到任何特殊的壓力，但我確實認為，這個行業中每個領導者的職責就是不斷向外尋找其他創新來源。

But I'm actually feeling very good about where Biogen is.

但實際上，我對 ​​Biogen 的現狀感到非常滿意。

Our share price may or may not reflect it, but I'm certainly not alone in this interest in thinking that the share price doesn't reflect where we are.

我們的股價或許能夠反映這一點，也或許不能，但我絕對不是唯一一個認為股價不能反映我們現狀的人。

And I think that's a function of a lot of the uncertainty around our industry.

我認為這是由於我們行業存在許多不確定性所造成的。

But we are just keeping our heads down and executing on our launches and making sure these products get to market and finding if there are shareholder value-enhancing transactions that can be done at pretty much any stage of the value chain.

但我們只是埋頭苦幹，執行我們的產品發布，確保這些產品進入市場，並尋找是否有可以在價值鏈的幾乎任何階段進行的股東價值提升交易。

Chris Schott, JPMorgan.

摩根大通的克里斯·肖特 (Chris Schott)。

I want to come back to the OpEx space.

我想回到 OpEx 領域。

I know the company is wrapping up its Fit for Growth program and there's some moving pieces here with the Royalty Pharma deal.

我知道該公司正在完成其「適合成長」計劃，並且與 Royalty Pharma 的交易有一些變動。

But as we think about the P&L going forward, is this kind of $3.9 billion or so OpEx space a good rough number to think about for Biogen going forward?

但是，當我們考慮未來的損益時，這種 39 億美元左右的營運支出空間對於 Biogen 未來而言是一個值得考慮的粗略數字嗎？

Or is there any other color about how to think about margin progression as we think about the next few years?

或者，當我們思考未來幾年時，對於利潤率的成長還有其他看法嗎？

Yes, Chris, I think that's right.

是的，克里斯，我認為是對的。

The Fit for Growth program was designed to take our OpEx to a level that supports our revenue expectations.

「適合成長」計畫旨在將我們的營運支出提升到支持我們收入預期的水平。

And I think that as we exit 2025 and go into future years, obviously, if we have launches to support and other things, we'll need to invest in those appropriately.

我認為，當我們走出 2025 年並進入未來幾年時，顯然，如果我們需要支持發布會和其他事情，我們就需要對它們進行適當的投資。

But I think the way that you described it is correct.

但我認為您描述的方式是正確的。

The program will be completed at the end of this year, and the $3.9 billion base rate is a good number to use as your baseline model.

該計劃將於今年底完成，39 億美元的基準利率是一個可以作為基準模型的數字。

Yes.

是的。

And clearly, business development, every time you do a deal, you bring in potentially new R&D expense.

顯然，在業務發展方面，你每次做一筆交易，都會帶來潛在的新的研發費用。

But I think what you've seen us do is prioritize.

但我想，您已經看到我們所做的是分清輕重緩急。

We've actually stopped a number of internal programs, which actually creates the financial capacity to bring other assets in.

我們實際上已經停止了一些內部項目，這實際上創造了引入其他資產的財務能力。

One of the biggest problems of business development typically has been is that the R&D budget is full, and there isn't any room to bring in new things.

企業發展面臨的最大問題之一通常是研發預算已經用盡，沒有空間引進新產品。

Well, we are actually making some of those difficult choices.

嗯，我們實際上正在做出一些艱難的選擇。

And the same is true on research.

研究上也是如此。

We have dramatically reduced our research budget, but the idea was not necessarily to just save cost.

我們大幅削減了研究預算，但這不一定只是為了節省成本。

The idea was that we wanted a different mix in there.

我們的想法是，想要在其中加入不同的混合。

And by prioritizing, we can actually do business development without having to increase our overall expenditure, at least that's what we've been able to do so far.

透過確定優先順序，我們實際上可以進行業務開發，而不必增加整體支出，至少到目前為止我們已經能夠做到這一點。

And then we're running short on time.

然後我們的時間就不多了。

Maybe get to squeeze one or two last ones in and let's go to the next one.

也許可以擠出最後一兩個時間，然後我們再去看下一個。

Evan Seigerman, BMO Capital Markets.

埃文·塞格曼 (Evan Seigerman)，BMO 資本市場。

Mike, congrats on your retirement.

麥克，祝賀你退休。

You will be missed.

我們將會想念你。

Robin, I'm really looking forward to working with you.

羅賓，我非常期待與您合作。

And Tim, congrats on your first [bite] in the earnings call; I got that all in.

提姆，祝賀你在財報電話會議上首次亮相；我全都明白了。

I want to touch very briefly on the use of GLP-1s in Alzheimer's disease.

我想簡單談談 GLP-1 在阿茲海默症的應用。

Novo Nordisk has talked a lot about the evoke trial, high risk, high reward.

諾和諾德已經多次談論 Evoke 試驗，高風險，高回報。

What happens if that hits and this could evolve the standard of care for the kind of prevention of Alzheimer's disease?

如果這結果成真，將會產生怎樣的結果？

Priya, maybe would love your thoughts there.

Priya，也許我會喜歡你的想法。

Yes.

是的。

Thank you, Evan.

謝謝你，埃文。

It's a very interesting hypothesis, and it's supported by some preclinical data as well as meta analysis that was looking at all-cause dementia and then some subsets, which also had Alzheimer's disease.

這是一個非常有趣的假設，它得到了一些臨床前數據和薈萃分析的支持，這些分析研究了全因癡呆症以及一些患有阿茲海默症的亞群。

And really, the scientific hypothesis behind it is thinking through about how glucose metabolism or regulation of that can impact neuro inflammation, vascular health, all of that and contribute to kind of more brain health situation.

實際上，背後的科學假設是思考葡萄糖代謝或其調節如何影響神經發炎、血管健康等，以及如何促進大腦健康狀況。

And I think that it's worthy of exploring.

我認為這值得探索。

I think we need to remember that some randomized controlled trials have failed in the space.

我認為我們需要記住，一些隨機對照試驗在該領域已經失敗。

Takeda with pioglitazone, and then actually Novo with liraglutide, small trial, 72 subjects.

武田公司使用吡格列酮，然後實際上是諾和諾德使用利拉魯肽，小規模試驗，共 72 名受試者。

The ELAD trial, they didn't meet their primary endpoints.

ELAD 試驗未能達到其主要終點。

That said, I think we look forward to seeing the outcomes.

話雖如此，我想我們期待看到結果。

What I think is really important to continue to remember is that when you're tackling something like Alzheimer's disease, you need to tackle the central pathology.

我認為真正需要牢記的是，當你治療阿茲海默症之類的疾病時，你需要治療核心病理。

We also note that the central pathology is not an overnight buildup, but build up over years.

我們也注意到，中心病理不是一夜之間形成的，而是經過多年的累積形成。

So for that reason, we continue to believe that an anti-amyloid agent like LEQEMBI that really addresses plaque but continues to address soluble toxic species after plaque clearance will have an important role to play.

因此，我們仍然相信，像 LEQEMBI 這樣的抗澱粉樣蛋白藥物不僅能真正解決斑塊問題，而且在斑塊清除後還能繼續解決可溶性毒性物質，將發揮重要作用。

So I think we're looking forward to the results of evoke and evoke+ just like everybody.

所以我認為我們和大家一樣期待 evoke 和 evoke+ 的結果。

But I think we continue to believe that this is going to be -- LEQEMBI is going to play and continue to play an important role.

但我認為我們仍然相信——LEQEMBI 將發揮並繼續發揮重要作用。

Phil Nadeau, Cowen.

菲爾‧納多 (Phil Nadeau)，考恩。

Let me add our congratulations to Mike, Robin, and Tim on their transitions.

我要向麥克、羅賓和提姆的轉變表示祝賀。

Just to drill down on the LEQEMBI short-term trajectory a little bit more closely.

只是為了更深入地研究 LEQEMBI 的短期軌跡。

In Q4, revenue was up 30%, but the revenue recognized was only up $1 million.

第四季度，營收成長了 30%，但確認的收入僅成長了 100 萬美元。

Can you talk about the dynamics behind that?

能談談這背後的動態嗎？

Were there onetime issues?

是否存在一次性問題？

Or is there an increase in spend that we should project into 2025?

或者我們應該預測到 2025 年支出將會增加？

And looking at 2025 trends, growth in 2024 was largely driven -- not entirely driven, but largely driven by ex US.

展望 2025 年的趨勢，2024 年的成長很大程度上受到——並非完全受到——美國以外地區的推動。

Is that replicable in 2025?

這在 2025 年還能複製嗎？

Or are the low-hanging fruit of those markets already picked?

還是這些市場唾手可得的果實已經被採摘了？

Well, I think LEQEMBI in the US was certainly up 200% Q4 on Q1.

嗯，我認為美國的 LEQEMBI 第四季環比成長了 200%。

And so we are seeing significant growth in the US.

因此我們看到美國出現了顯著的成長。

Yes, the ex US has certainly been strong as well.

是的，美國以外的國家當然也很強大。

But I think it's both.

但我認為兩者兼具。

So I think for 2025, in the absence of anything else, we see pretty much continuing trends would be our best guess at this.

因此我認為，對於 2025 年而言，在沒有其他任何因素的情況下，我們看到的持續趨勢是我們對此的最佳猜測。

There may be some acceleration with the IV maintenance, but we're not going to get the subcutaneous for maintenance until really in the last part of the year.

靜脈注射維持治療可能會加速，但直到今年年底我們才會真正開始使用皮下注射進行維持治療。

Blood-based diagnostics could play a role, but we all know that it takes a while to get diagnostics to be actually accepted and reimbursed.

基於血液的診斷可以發揮作用，但我們都知道，診斷要真正被接受和報銷需要一段時間。

So I think we're going to just see good, steady progress quarter on quarter.

因此我認為我們將看到季度環比良好、穩定的進展。

There hasn't been that much impact yet of donanemab; that could have a role at some point, but I think they're dealing with the same issues that we are.

donanemab 的影響力目前還沒有那麼大；這在某種程度上可能會發揮作用，但我認為他們面臨的問題與我們是一樣的。

I think the big thing is really to, as I say, to expand the prescriber base.

我認為，正如我所說，真正重要的是擴大處方人員基礎。

I think really focus on the benefit of treatment and roll out these new formulations.

我認為真正關注的是治療的好處並推出這些新配方。

So I think it's going to be continued progress.

所以我認為這將會持續進步。

We obviously continue to believe that Alzheimer's can be a significant market, and that's why we're investing not only in tau, but in other modalities.

我們顯然仍然相信阿茲海默症可能是一個重要的市場，這就是為什麼我們不僅投資 tau，還投資其他方式。

The unmet need is incredible, 500,000 new patients every year.

未滿足的醫療需求令人難以置信，每年有 50 萬名新患者。

It's one of the leading causes of death, certainly amongst over 65 year olds, but it's even a top 10 cause of death just in the general population.

它是導致死亡的主要原因之一，尤其是對於 65 歲以上的人群而言，但它甚至是死亡的十大原因之一。

So not to mention the devastation that this causes to family.

更不用說這對家庭造成的破壞了。

So the unmet need is huge.

因此，未滿足的需求是巨大的。

It is clear that, in the short term, we have a lot of capacity constraints, but I think we've made a lot of progress in relieving some of those.

顯然，短期內我們面臨許多產能限制，但我認為我們在緩解其中一些限制方面已經取得了很大進展。

And so I think now with these new formulations such as subcu and with the blood-based diagnosis, we have an opportunity to accelerate our growth, I would say, over the next two to three years.

所以我認為現在有了皮下注射等新配方和基於血液的診斷，我們有機會在未來兩到三年內加速我們的成長。

Yes.

是的。

And Phil, on the numbers, just to reiterate something we said in the prepared remarks, the LEQEMBI fourth-quarter end market revenue was $87 million globally.

菲爾，關於數字，我只想重申我們在準備好的評論中所說的內容，LEQEMBI 第四季度的全球終端市場收入為 8700 萬美元。

That's up about 30% sequentially from the third quarter of 2024.

這比 2024 年第三季環比成長約 30%。

In the US, it was -- of the $87 million, $50 million in the US, and that's up about 28% sequentially.

在美國，8,700 萬美元中的 5,000 萬美元來自美國，比上一季成長了約 28%。

Thanks, Mike, and thanks, everybody, for your time today.

謝謝，麥克，也謝謝大家今天抽出時間。

The IR team is available if you've got questions later today.

如果您今天晚些時候有疑問，IR 團隊將隨時為您提供協助。

Thank you.

謝謝。

This does conclude today's conference.

今天的會議到此結束。

We thank you for your participation.

我們感謝您的參與。