Biogen Inc (BIIB) 2023 Q2 法說會逐字稿

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

早上好。我叫露絲，今天我將擔任你們的會議操作員。此時此刻，我謹歡迎大家參加百健 (Biogen) 2023 年第二季度收益電話會議和業務更新。 （操作員指示）今天的會議正在錄製。

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

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

Thank you, operator. Good morning, and welcome to Biogen's Second Quarter 2023 Earnings Call. Before we begin, I encourage everyone to go through 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. 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 will follow the discussion related to this call.

謝謝你，接線員。早上好，歡迎參加百健 (Biogen) 2023 年第二季度收益電話會議。在我們開始之前，我鼓勵大家瀏覽 biogen.com 的投資者部分，查找收益發布和相關財務表格，包括我們今天將討論的 GAAP 財務指標以及 GAAP 與非 GAAP 財務指標的調節表。表 1 和表 2 提供了我們的 GAAP 財務數據，表 4 包括我們的 GAAP 與非 GAAP 財務結果的調節表。我們相信非公認會計準則財務業績更好地代表了我們業務的持續經濟狀況，並反映了我們內部管理業務的方式。我們還在我們的網站上發布了幻燈片，這些幻燈片將跟踪與本次電話會議相關的討論。

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

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

On today's call, I'm joined by our President and Chief Executive Officer, Chris Viehbacher, Dr. Priya Singhal, Head of Development; and our CFO, Mike McDonnell. Chris, Priya and Mike will each make some opening comments, and then we'll move to the Q&A session. To allow us to get through as many questions as possible, we kindly ask that you limit yourself to 1 question.

參加今天的電話會議的還有我們的總裁兼首席執行官 Chris Viehbacher、開發主管 Priya Singhal 博士；和我們的首席財務官邁克·麥克唐納。 Chris、Priya 和 Mike 將分別發表一些開場評論，然後我們將進入問答環節。為了讓我們能夠回答盡可能多的問題，我們懇請您將問題限制在 1 個以內。

I will now turn the call over to Chris.

我現在將把電話轉給克里斯。

Thank you, Chuck. Good morning, everybody.

謝謝你，查克。大家早上好。

I'd like to start off with LEQEMBI. And I think before we really get into all the interesting details of commercialization and competitiveness, I just like to pause for a moment. This is an historic moment in health care history. We're talking about the very first disease-modifying treatment that's been approved, full -- has received full approval from the FDA and reimbursement from CMS. And there have been literally dozens of medicines that have failed before this drug ever got to market. And that's important for a couple of reasons.

我想從 LEQEMBI 開始。我認為在我們真正討論商業化和競爭力的所有有趣細節之前，我想暫停一下。這是醫療保健史上的歷史性時刻。我們談論的是第一個獲得批准的疾病緩解治療，已獲得 FDA 的完全批准和 CMS 的報銷。在這種藥物上市之前，實際上已經有數十種藥物失敗了。這很重要，原因有幾個。

The first is that, there's an awful lot we still don't know. We are really at the beginning of a journey to really understand Alzheimer's disease and how we can affect this disease. But it's also going to have a big impact on the practice of medicine. Physicians haven't been able to really help patients very much beyond perhaps prescribing donepezil or products like that. And the treatment that we are proposing here really is going to change an awful lot of how physicians practice and treat these patients. So as we start thinking about intent to prescribe and how physicians are looking at things, we're actually not going to know that until we actually get out there in the marketplace and see how patients respond. ADUHELM did get approved, but as you all know, it never really got out of the blocks and never really got launched. So this is really a first. And whenever you're first, we're going to be discovering an awful lot. And a lot of this is just not that predictable.

首先，我們仍然不知道很多事情。我們確實正處於真正了解阿爾茨海默病以及我們如何影響這種疾病的旅程的開始。但這也將對醫學實踐產生重大影響。除了開多奈哌齊或類似產品之外，醫生無法真正幫助患者。我們在這裡提出的治療方法確實會極大地改變醫生的治療和治療這些患者的方式。因此，當我們開始考慮處方意圖以及醫生如何看待事物時，我們實際上不會知道這一點，直到我們真正進入市場並觀察患者的反應。 ADUHELM 確實獲得了批准，但眾所周知，它從未真正擺脫困境，也從未真正推出。所以這確實是第一次。每當你成為第一個時，我們都會發現很多東西。其中很多都是不可預測的。

I would, again, just call out kudos to our colleagues at Eisai. Within a very short period of time, you were able to get regulatory filings in the EU, Japan, China, Canada, Great Britain and South Korea. So this is going to be truly a global launch.

我想再次向衛材的同事表示敬意。在很短的時間內，您就可以在歐盟、日本、中國、加拿大、英國和韓國獲得監管備案。因此，這將是一次真正的全球發布。

Now we just had the AAIC last week, Priya will cover off a little bit more about that. But one of the things that has become obvious is when we start looking at donanemab and lecanemab. These are 2 very different products. And I don't think most people have actually really looked at that. Most people are looking at, okay, we've got an A-beta antibody and we're removing plaques. But there's a whole lot more to the story. And this is going to evolve over the next months and years. This is a -- these are different products. They have different mechanisms because they have different binding. They've been studied in different populations. They've been studied with different clinical study design approaches. And of course, they have a very different safety profile. And all of these differences are going to play out in the marketplace over the coming months and years. And it will be interesting to see how that is, but I would just caution everybody as we get into this and you see all of the data, there's an awful lot of subtlety to this, and it's going to be quite interesting from a commercial point of view.

上週我們剛剛召開了 AAIC，Priya 將對此進行更多介紹。但當我們開始關注多納奈單抗和樂卡奈單抗時，事情變得顯而易見。這是兩種截然不同的產品。我認為大多數人並沒有真正關注過這一點。大多數人都在關注，好吧，我們已經有了 A-β 抗體，並且正在去除斑塊。但這個故事還有很多其他內容。這將在未來幾個月和幾年內不斷發展。這是——這些是不同的產品。它們具有不同的機制，因為它們具有不同的結合力。他們在不同人群中進行了研究。他們已經用不同的臨床研究設計方法進行了研究。當然，它們的安全性也截然不同。所有這些差異都將在未來幾個月和幾年內在市場上體現出來。看看這是怎麼回事會很有趣，但我想提醒大家，當我們進入這個領域時，你會看到所有的數據，其中有很多微妙之處，從商業角度來看，這將非常有趣看法。

The launch is underway in the U.S. We did get full approval earlier this month and CMS approval, that has significance also for others. This is going to encourage a lot of other companies to be investing in research and blood diagnostics. It's also, as you know, going to be an unusual launch. There's an awful lot that has to be done. We're going to have patient navigators to help navigate the process to understand how treatment will occur, getting reimbursement. We will be working with physician offices, an awful lot of change that will have to occur in the practice -- in their practices on a day-to-day basis. There's an awful lot of education around safety, making sure that the right patients are in place. We have reached out to about 700 centers to date. We're also getting reimbursement beyond CMS. We have Medicaid, for example, in 48 out of the 50 states so far. And we have had very good response from commercial insurers.

該產品正在美國推出。本月早些時候，我們確實獲得了全面批准，並獲得了 CMS 批准，這對其他人也具有重要意義。這將鼓勵許多其他公司投資於研究和血液診斷。如您所知，這也將是一次不同尋常的發布。有很多事情要做。我們將讓患者導航員幫助引導整個過程，以了解如何進行治療並獲得報銷。我們將與醫生辦公室合作，在實踐中——在他們的日常實踐中——必鬚髮生大量的改變。有大量關於安全的教育，以確保合適的患者就位。迄今為止，我們已經聯繫了大約 700 個中心。我們還獲得了 CMS 之外的報銷。例如，到目前為止，我們已在 50 個州中的 48 個州提供醫療補助。我們得到了商業保險公司的良好回應。

So I think the launch of LEQEMBI is off to a very good start, and we'll, of course, keep you up to date as we get further information.

因此，我認為 LEQEMBI 的推出是一個非常好的開始，當然，當我們獲得更多信息時，我們會及時向您通報最新情況。

I'll move on to another slide here. One of the things that we've been doing an awful lot in the past months is really making sure that we are well positioned for growth. And as we looked at the company, there's where we were. As you know, today, we have a relatively mature product profile. Generally, when you have a mature product profile, you'd expect the level of investment to go down. We have actually relatively high operating expenses when we benchmark versus other companies. Part of that is an overinvestment in legacy products, but we also have an extremely centralized governance. We've got many organizational levels. We have a low span of control. On average, we have a span of control of 3 and then as we look at the R&D pipeline, we've had 5 different heads of R&D in 10 years. And that's not good for an R&D organization. And as a result, we ended up with some products that I think were relatively high risk and high cost and not necessarily of the highest value. So we've been through an extensive project to really review those R&D programs.

我將轉到這裡的另一張幻燈片。過去幾個月我們做的很多事情之一就是確保我們為增長做好準備。當我們審視這家公司時，我們發現這就是我們所處的位置。如您所知，今天我們擁有相對成熟的產品體系。一般來說，當您擁有成熟的產品概況時，您預計投資水平會下降。當我們與其他公司進行比較時，我們的運營費用實際上相對較高。部分原因是對遺留產品的過度投資，但我們也有一個極其集中的治理。我們有很多組織級別。我們的控制範圍很小。平均而言，我們的控制跨度為 3，然後當我們查看研發渠道時，我們在 10 年內擁有 5 個不同的研發負責人。這對於研發組織來說並不是好事。結果，我們最終得到了一些我認為風險相對較高、成本較高且不一定具有最高價值的產品。因此，我們已經完成了一個廣泛的項目來真正審查這些研發計劃。

And as we looked at where do we want to be? Well, we want to be making more value-based decisions for existing products. We don't want to just remove the promotional effort tightly. Biogen is still 25% market share in multiple sclerosis. We have the highest market share by a considerable margin. And so there is -- there are an awful lot of patients who depend on Biogen products. But I think we can do that smarter. There's a need, obviously, to have strong investment in our new product launches. It's important clearly to manage costs, but shareholder value will be most optimized if we can really make a success with these launches. We need to get decision-making closer to customers. We want greater agility in the organization and we want to focus on high-value projects in R&D.

當我們思考我們想要成為什麼樣的人時？嗯，我們希望為現有產品做出更多基於價值的決策。我們不想完全取消促銷活動。百健（Biogen）在多發性硬化症領域仍佔據 25% 的市場份額。我們以相當大的優勢擁有最高的市場份額。因此，有大量患者依賴百健（Biogen）產品。但我認為我們可以做得更聰明。顯然，我們需要對新產品的發布進行大力投資。管理成本顯然很重要，但如果我們能夠真正在這些產品發布中取得成功，股東價值將得到最大程度的優化。我們需要讓決策更加貼近客戶。我們希望組織具有更大的敏捷性，並且希望專注於研發中的高價值項目。

External growth will really give us the opportunity to diversify away from rare diseases -- diversify into rare diseases, immunology and neuropsychiatry. So we did this redesign effort. What we did was a bottom-up exercise to look at where do we need to be as a company [who will be] successfully launching new products, what kind of internal governance mechanisms do we want? What kind of metrics do we want? What kind of accountability? And so there's been, as I say, a complete redesign of Biogen and that will lead some cost savings. There are gross cost savings, which will be about $1 billion in annualized savings per year. Of that, we expect to invest at least $300 million in growth opportunities going forward. So this is an opportunity really to make sure in this year before we get into the product launches that we were truly fit for growth.

外部增長確實會給我們帶來遠離罕見疾病的多元化機會，進入罕見疾病、免疫學和神經精神病學領域。所以我們做了這次重新設計工作。我們所做的是自下而上的練習，看看作為一家[將]成功推出新產品的公司，我們需要達到什麼水平，我們需要什麼樣的內部治理機制？我們想要什麼樣的指標？什麼樣的責任？因此，正如我所說，百健（Biogen）公司進行了徹底的重新設計，這將節省一些成本。總成本節省，每年大約可節省 10 億美元。其中，我們預計將投資至少 3 億美元用於未來的增長機會。因此，這是一個真正的機會，可以在今年推出產品之前確保我們真正適合增長。

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

這樣，我就把它交給 Priya。

Thank you, Chris. We believe that the traditional approval of LEQEMBI is a significant milestone for the Alzheimer's field. We also recognize that the pursuit of effective therapies for Alzheimer's is far from over. Biogen and Eisai are continuing to generate data on LEQEMBI across the Alzheimer's disease continuum. Amyloid pathology can begin years before the onset of symptoms. There is the potential to maximize therapeutic effect of LEQEMBI by treating earlier to delay or even prevent the onset of Alzheimer's. Eisai and Biogen initiated the AHEAD 3-45 Trial in 2020 to evaluate this approach. This consists of 2 sister trials in cognitively unimpaired individuals aged 55 to 80 with intermediate or elevated levels of amyloid on PET screening and they will be evaluated over 48 months.

謝謝你，克里斯。我們相信 LEQEMBI 的傳統批准是阿爾茨海默病領域的一個重要里程碑。我們還認識到，對阿爾茨海默病有效療法的追求還遠未結束。百健 (Biogen) 和衛材 (Eisai) 正在繼續生成有關阿爾茨海默病連續體的 LEQEMBI 數據。澱粉樣蛋白病理可以在症狀出現前數年開始。通過早期治療來延緩甚至預防阿爾茨海默病的發作，有可能最大限度地提高 LEQEMBI 的治療效果。衛材和百健 (Biogen) 於 2020 年啟動了 AHEAD 3-45 試驗來評估這種方法。該試驗由 2 項姊妹試驗組成，試驗對象為 55 歲至 80 歲、認知能力未受損且 PET 篩查中澱粉樣蛋白水平中等或升高的個體，將對這些個體進行超過 48 個月的評估。

With the approval of LEQEMBI in the U.S., we also modified our protocol for the AHEAD Trial to allow for open-label LEQEMBI rescue should patients progress to early AD, while being enrolled in the trial. We believe the clinical profile of LEQEMBI is uniquely suited for the early intervention approach, with robust plaque clearance, low incidence of ARIA and optionality of longer duration treatment to potentially maximize clinical benefit. We are working to improve and simplify the patient journey for LEQEMBI in early AD.

隨著 LEQEMBI 在美國獲得批准，我們還修改了 AHEAD 試驗的方案，以便在患者參加試驗時，如果患者進展到早期 AD，則可以進行開放標籤 LEQEMBI 救援。我們相信 LEQEMBI 的臨床特徵特別適合早期干預方法，具有強大的斑塊清除能力、低 ARIA 發生率以及較長持續時間治療的選擇，以潛在地最大化臨床效益。我們正在努力改善和簡化 AD 早期 LEQEMBI 的患者治療歷程。

We have 2 areas of focus: a subcutaneous formulation where the auto-injector to potentially enable at-home administration is underway. Eisai recently presented modeling data at AAIC, suggesting that subcutaneous lecanemab for Biosimilar exposure and amyloid plaque reduction and biweekly IV formulation but with a potential for lower incidence of ARIA. Regulatory filing is expected by the end of Q1 2024. Second is maintenance dosing, evaluating less frequent maintenance dosing in the Phase II open-label extension. Regulatory filing is also expected by the end of Q1 2024. We are also continuing to analyze the Clarity AD data where we have observed consistent reductions in both amyloid and tau PET and improved clinical outcomes as we aim to better inform treatment decisions for patients.

我們有兩個重點領域：皮下製劑，其中自動注射器有望實現家庭給藥。衛材最近在 AAIC 上展示了模型數據，表明皮下注射 Lecanemab 可用於生物仿製藥暴露和澱粉樣斑塊減少以及每兩週一​​次靜脈注射製劑，但有可能降低 ARIA 的發生率。預計將於 2024 年第一季度末提交監管申請。其次是維持劑量，評估第二階段開放標籤擴展中不太頻繁的維持劑量。預計將於 2024 年第一季度末提交監管申請。我們還將繼續分析 Clarity AD 數據，我們觀察到澱粉樣蛋白和 tau PET 持續減少，並改善臨床結果，因為我們的目標是更好地為患者的治療決策提供信息。

Clarity AD study did not use baseline tau PET as an exclusion criteria and enrolled a broad population of early AD patients with varying degrees of tau pathology at baseline. This important aspect of the Clarity AD study allowed the generation of data on individuals with low tau burdens that has not been collected in other Phase III programs. At AAIC, Eisai presented baseline characteristics and a new analysis containing the initial results from the tau PET sub-study of Clarity AD.

Clarity AD 研究沒有使用基線 tau PET 作為排除標準，而是招募了大量基線時具有不同程度 tau 病理學的早期 AD 患者。 Clarity AD 研究的這一重要方面可以生成有關低 tau 負荷個體的數據，而其他 III 期項目尚未收集到這些數據。在 AAIC 上，衛材展示了基線特徵和一項新分析，其中包含 Clarity AD tau PET 子研究的初步結果。

In this analysis, individuals enrolled in the tau PET sub-study were categorized into high, medium and low groups based upon tau burden measured at baseline. Lecanemab administration showed a clinical effect in the overall population of the tau PET sub-study and notably a large effect size was also observed in the low tau population defined in this analysis, which does represent the early phase of AD. We believe this data further supports the clinical benefit observed with LEQEMBI in the broad early AD population and again emphasizes the importance of treating patients early.

在這項分析中，根據基線測量的 tau 蛋白負荷，將參加 tau PET 子研究的個體分為高、中和低組。 Lecanemab 給藥在 tau PET 子研究的總體人群中顯示出臨床效果，值得注意的是，在本分析中定義的低 tau 人群中也觀察到了較大的效應大小，這確實代表了 AD 的早期階段。我們相信這一數據進一步支持了 LEQEMBI 在廣泛的早期 AD 人群中觀察到的臨床益處，並再次強調了早期治療患者的重要性。

Biogen plans to build upon our industry-leading position in therapeutics for A-beta clearance and tau knock down by advancing a multi-target, multi-modality portfolio, inclusive of also other emerging targets in the Alzheimer's disease pathway. This is inclusive of programs targeting tau. BIIB080, a Phase II targeting antisense oligonucleotide and BIIB113, a Phase I small molecule aiming to prevent tau acquisition.

百健 (Biogen) 計劃通過推進多靶點、多模式產品組合（包括阿爾茨海默氏病途徑中的其他新興靶點），鞏固我們在 A-β 清除和 tau 蛋白敲除治療領域的行業領先地位。這包括針對 tau 蛋白的計劃。 BIIB080是一種II期靶向反義寡核苷酸，BIIB113是一種旨在阻止tau獲得的I期小分子。

Turning to SMA. The interim results from the RESPOND study were presented at the Cure SMA conference recently and highlight that most participants and investigator and caregiver reported suboptimal clinical status across multiple domains at baseline following Zolgensma treatment. This included motor function, swallowing or feeding ability and respiratory function. Potentially, we believe this is due to likely incomplete transduction of motor neurons following gene therapy administration.

轉向 SMA。 RESPOND 研究的中期結果最近在 Cure SMA 會議上公佈，並強調大多數參與者、研究者和護理人員在 Zolgensma 治療後報告基線時多個領域的臨床狀態不理想。這包括運動功能、吞嚥或進食能力以及呼吸功能。我們認為這可能是由於基因治療後運動神經元的轉導不完全所致。

The internal results at 6 months show improvements in motor function in most participants as measured by the increased total time to score from baseline with no new emerging safety concerns identified. Overall, we believe these results suggest that there may be potential for additional benefit with SPINRAZA treatment following Zolgensma administration.

6 個月的內部結果顯示，大多數參與者的運動功能有所改善，這是通過從基線開始評分的總時間增加來衡量的，並且沒有發現新出現的安全問題。總體而言，我們相信這些結果表明，在 Zolgensma 給藥後使用 SPINRAZA 治療可能有潛在的額外益處。

The R&D organization, as Chris mentioned, has spent significant time and energy over the last several months in conducting a comprehensive review of Biogen's R&D programs as we aim to improve the risk profile and productivity of the pipeline. We made a number of significant decisions and identified the programs we want to prioritize and others where we assess the challenges resulted in a low probability adjusted return on investment and thus were promptly modified or discontinued. We believe that this has resulted in a leaner pipeline with an overall greater probability of success and a sharper focus on key programs.

正如克里斯提到的，研發組織在過去幾個月中花費了大量時間和精力對百健（Biogen）的研發計劃進行全面審查，因為我們的目標是改善管道的風險狀況和生產力。我們做出了許多重大決定，並確定了我們想要優先考慮的計劃，以及我們評估的其他計劃，這些挑戰導致調整後的投資回報率較低，因此被及時修改或終止。我們相信，這會導致管道更加精簡，整體成功的可能性更大，並且更加關注關鍵項目。

The examples shown here all have data readouts expected over the next few years. BIIB080, a Phase II targeting -- tau targeting ASO, which has Phase Ib data showing a time and dose-dependent reduction in CSF total tau and phospho-tau as well as tau tangles visualized via tau PET.

此處顯示的示例均具有未來幾年預計的數據讀數。 BIIB080，一種 II 期靶向藥物 - tau 靶向 ASO，其 Ib 期數據顯示 CSF 總 tau 和磷酸化 tau 以及通過 tau PET 可視化的 tau 纏結呈時間和劑量依賴性減少。

Litifilimab, a subcutaneous anti-BDCA2 antibody, currently being evaluated in 2 Phase III studies in systemic lupus erythematosus and a Phase II/III study in cutaneous lupus erythematosus.

Litifilimab 是一種皮下抗 BDCA2 抗體，目前正在兩項系統性紅斑狼瘡 III 期研究和一項皮膚紅斑狼瘡 II/III 期研究中進行評估。

BIIB105, an ataxin-2 ASO, being evaluated in a Phase I/II study in broad sporadic ALS, we expect to read out midyear 2024. BIIB122, a LRRK2 ASO being developed in partnership with Denali Therapeutics currently in a Phase IIb study for idiopathic Parkinson's disease and BIIB121, an ASO aiming to increase the expression of paternal UBE3A in Angelman syndrome, and we expect the Phase I to read out midyear 2024.

BIIB105 是一種 ataxin-2 ASO，正在廣泛散發性 ALS 的 I/II 期研究中進行評估，我們預計將於 2024 年年中公佈。BIIB122 是一種 LRRK2 ASO，正在與 Denali Therapeutics 合作開發，目前正在進行特發性 ALS 的 IIb 期研究帕金森病和 BIIB121 是一種 ASO，旨在增加 Angelman 綜合徵中父親 UBE3A 的表達，我們預計 I 期臨床試驗將於 2024 年年中完成。

In summary, this past quarter, we continued to make significant advancements across our pipeline, most notably with the traditional approval of LEQEMBI in early AD. While our initial substantial review of the pipeline is complete, we will continue to evaluate both current and potential new R&D programs using a data-driven approach with a keen eye toward risk balance and value creation.

總之，上個季度，我們繼續在整個產品線中取得重大進展，最引人注目的是 LEQEMBI 在公元早期獲得的傳統批准。雖然我們對管道的初步實質性審查已經完成，但我們將繼續使用數據驅動的方法評估當前和潛在的新研發計劃，並密切關注風險平衡和價值創造。

I will now pass the call over to Mike.

我現在將把電話轉給邁克。

Thank you, Priya, and good morning, everyone. I'll provide some highlights and color regarding our financial performance for the second quarter and all of the financial comparisons that you will hear are versus the second quarter of 2022.

謝謝你，Priya，大家早上好。我將提供有關我們第二季度財務業績的一些亮點和色彩，以及您將聽到的所有財務比較都是與 2022 年第二季度的比較。

Total revenue for the second quarter was $2.5 billion. That's a decrease of 5% at actual currency and 3% at constant currency. Non-GAAP diluted earnings per share in the second quarter was $4.02. Total MS product revenue was $1.2 billion. That's a decrease of 15% at actual currency and 14% at constant currency.

第二季度總收入為25億美元。按實際貨幣計算下降 5%，按固定匯率計算下降 3%。第二季度非 GAAP 稀釋後每股收益為 4.02 美元。 MS 產品總收入為 12 億美元。按實際貨幣計算下降 15%，按固定匯率計算下降 14%。

So a few recent updates to the MS business this quarter. First, the decline in MS in the second quarter was attributable to generic entrants for TECFIDERA and broad competition in the MS market. We did not see much in the way of channel dynamics during the second quarter. Second, as we did announce previously, TECFIDERA's regulatory market protection in the EU was extended by one additional year until February 2, 2025. Some of the TECFIDERA generics have not yet fully exited some of the EU markets and some generic products remain in the channel. The pace of generic withdrawal has been slower than we expected, and we're closely monitoring the situation and working to enforce our legal right to market protection.

本季度微軟業務的一些最新更新。首先，第二季度 MS 業務的下降歸因於 TECFIDERA 仿製藥的進入以及 MS 市場的廣泛競爭。第二季度我們沒有看到太多渠道動態。其次，正如我們之前宣布的那樣，TECFIDERA 在歐盟的監管市場保護再延長一年至 2025 年 2 月 2 日。部分 TECFIDERA 仿製藥尚未完全退出部分歐盟市場，部分仿製藥仍留在渠道中。仿製藥撤回的速度比我們預期的要慢，我們正在密切關注事態發展並努力執行我們的市場保護合法權利。

Regarding TYSABRI, we have previously said that there may be a TYSABRI Biosimilar launch in the U.S. and EU sometime later in 2023. We are aware of the positive CHMP opinion for the TYSABRI Biosimilar in the EU last week. And while we have not seen any Biosimilar launches so far, we could see an approval and launch in the coming months.

關於 TYSABRI，我們之前曾表示，TYSABRI 生物仿製藥可能會在 2023 年晚些時候在美國和歐盟上市。我們知道 CHMP 上週對歐盟的 TYSABRI 生物仿製藥發表了積極的意見。雖然到目前為止我們還沒有看到任何生物仿製藥的上市，但我們可能會在未來幾個月內看到批准和上市。

Moving on now to SMA. Global SPINRAZA revenue of $437 million, increased 1% at actual currency and 5% at constant currency. SPINRAZA growth in the U.S. was 12%, and that was driven by patient growth. We were encouraged by the performance this past quarter and believe we are making good progress against our goal of returning SPINRAZA to consistent growth. Also, as Priya mentioned, we are continuing to generate data to support the efficacy profile of SPINRAZA and we believe that this, along with the expected overall market expansion should help enable continued, improved performance for SPINRAZA.

現在轉向 SMA。全球 SPINRAZA 收入為 4.37 億美元，按實際貨幣計算增長 1%，按固定匯率計算增長 5%。 SPINRAZA 在美國的增長為 12%，這是由患者增長推動的。我們對上個季度的業績感到鼓舞，並相信我們在實現讓 SPINRAZA 恢復持續增長的目標方面取得了良好進展。此外，正如 Priya 提到的，我們正在繼續生成數據來支持 SPINRAZA 的功效概況，我們相信，這一點以及預期的整體市場擴張應有助於使 SPINRAZA 的業績持續改善。

Biosimilars revenue of $195 million, was flat at actual currency and increased 4% at constant currency. We are continuing to manage supply constraints for IMRALDI and BENEPALI and are monitoring this situation very closely. We've referenced previously that we are evaluating whether this business could create more value outside of Biogen and we are engaged with multiple interested parties and will provide further updates on that process as appropriate.

生物仿製藥收入為 1.95 億美元，按實際貨幣計算持平，按固定匯率計算增長 4%。我們正在繼續管理 IMRALDI 和 BENEPALI 的供應限制，並密切監視這一情況。我們之前提到過，我們正在評估這項業務是否可以在百健（Biogen）之外創造更多價值，我們正在與多個感興趣的各方進行接觸，並將酌情提供有關該流程的進一步更新。

Alzheimer's disease revenue, which includes revenue from ADUHELM, and the LEQEMBI collaboration equated to a headwind of $20 million to revenue during the second quarter. As a reminder, LEQEMBI revenue represents our 50% of in-market revenue, less 50% of commercialization expenses. We expect this line to continue to be negative in 2023 as the ramping of LEQEMBI commercialization expenses will exceed initial revenue. Total anti-CD20 revenue of $433 million, was down 1% and included a $12 million operating loss related to LUNSUMIO. As a reminder, starting this quarter, our pretax profit share on RITUXAN, GAZYVA and LENSUMIO decreased from 37.5% to 35% and that's due to the achievement of certain sales targets for GAZYVA as part of our contractual agreement with Genentech.

阿爾茨海默病收入（包括 ADUHELM 的收入）和 LEQEMBI 合作的收入相當於第二季度收入減少了 2000 萬美元。提醒一下，LEQEMBI 收入占我們市場收入的 50%，減去商業化費用的 50%。我們預計該線在 2023 年將繼續為負，因為 LEQEMBI 商業化費用的增加將超過初始收入。抗 CD20 總收入為 4.33 億美元，下降 1%，其中包括與 LUNSUMIO 相關的 1200 萬美元運營虧損。提醒一下，從本季度開始，我們在 RITUXAN、GAZYVA 和 LENSUMIO 上的稅前利潤份額從 37.5% 下降到 35%，這是由於作為我們與 Genentech 的合同協議的一部分，GAZYVA 實現了某些銷售目標。

Contract manufacturing, royalty and other revenue of $198 million was notably higher year-over-year and that was driven mainly by the timing of batches.

合同製造、特許權使用費和其他收入同比顯著增加 1.98 億美元，這主要是由批次時間推動的。

A couple of details regarding Q2 expenses. For the second quarter, non-GAAP cost of sales was 24% of total revenue and that includes $34 million of idle capacity charges. We continue to see higher cost of sales as a percentage of revenue as a result of product mix and idle capacity charges. And in particular, the increases that we are seeing in contract manufacturing revenue increases our overall cost of sales as a percentage of revenue.

有關第二季度支出的一些細節。第二季度，非 GAAP 銷售成本佔總收入的 24%，其中包括 3400 萬美元的閒置產能費用。由於產品組合和閒置產能費用，我們繼續看到銷售成本佔收入的百分比上升。特別是，我們看到合同製造收入的增長增加了我們的總體銷售成本佔收入的百分比。

So in terms of modeling for the remainder of 2023, I'd offer that we believe contract manufacturing revenue will remain strong and will contribute to a higher cost of sales as a percentage of revenue for the remainder of this year as compared to the 24.1% that we saw in the second quarter.

因此，就 2023 年剩餘時間的建模而言，我認為我們相信合同製造收入將保持強勁，並將導致今年剩餘時間的銷售成本佔收入的比例高於 24.1%我們在第二季度看到的。

Second quarter non-GAAP R&D expense includes roughly $13 million in estimated study close-up costs related to BIIB093.

第二季度非 GAAP 研發費用包括大約 1300 萬美元的與 BIIB093 相關的估計研究特寫成本。

As Priya mentioned, we're now substantially complete with our R&D prioritization. We estimate that this will result in gross savings of approximately $250 million next year, though this will be partially offset by natural increases in R&D due to portfolio progression. The decrease in second quarter SG&A expense was attributed to roughly $70 million of savings initiatives, and that was partially offset by approximately $35 million of reinvestments mostly related to launch costs. We continue to expect our operating expenses to be lower in the second half of the year than in the first half as we complete the run rate savings from our previously announced cost initiatives as well as a modest impact from our new Fit for Growth initiative.

正如 Priya 提到的，我們現在已經基本完成了研發優先順序。我們估計，這將在明年帶來約 2.5 億美元的總節省，儘管這將被投資組合進展導致的研發自然增長所部分抵消。第二季度 SG&A 費用的減少歸因於約 7000 萬美元的節約舉措，而這部分被約 3500 萬美元的再投資所部分抵消，這些再投資主要與啟動成本有關。我們仍然預計下半年的運營費用將低於上半年，因為我們完成了之前宣布的成本計劃的運行率節省，以及新的“適應增長”計劃的適度影響。

So now I'd like to take a minute to provide a little bit of additional detail on our new Fit for Growth program. This program will include changes to our operating model with a significant reduction of certain centralized functions. A substantial portion of the $700 million of net annual OpEx savings are expected to come from a net headcount reduction of approximately 1,000, which we expect to rightsize the company with our business plan and enable us to return to sustainable growth. I would reiterate that the OpEx savings shown here are on an annualized basis. We believe that this is an efficient program with 70% of our expected gross OpEx savings to be realized as net savings. All in, we expect a very modest impact on 2023 expenses and believe the net OpEx savings will be split roughly equally between 2024 and 2025, and all of these savings are incremental to any previously announced cost reduction programs.

現在我想花一點時間提供一些有關我們新的“適合成長”計劃的更多細節。該計劃將包括對我們的運營模式的改變，並顯著減少某些集中功能。 7 億美元的年度運營支出淨節省中的很大一部分預計將來自約 1,000 人的淨裁員，我們預計這將根據我們的業務計劃調整公司規模，並使我們能夠恢復可持續增長。我要重申的是，這裡顯示的運營支出節省是按年計算的。我們相信這是一個高效的計劃，我們預計總運營支出節省的 70% 將作為淨節省實現。總而言之，我們預計對 2023 年支出的影響非常溫和，並相信 2024 年和 2025 年之間的淨運營支出節省將大致平均分配，所有這些節省都是之前宣布的成本削減計劃的增量。

A few quick comments on our balance sheet, including the approximately $813 million that we received during the quarter related to the sale of our equity stake in Samsung Bioepis. We ended the quarter with $7.3 billion in cash and marketable securities. On June 30, we had $6.3 billion in debt, and that puts us in a net cash position of roughly $1 billion. We continue to generate steady positive cash flow from operations with free cash flow of $416 million during the second quarter.

關於我們的資產負債表的一些簡短評論，包括我們在本季度收到的與出售 Samsung Bioepis 股權相關的約 8.13 億美元。本季度結束時，我們擁有 73 億美元的現金和有價證券。截至 6 月 30 日，我們的債務為 63 億美元，這使我們的淨現金頭寸約為 10 億美元。我們繼續從運營中產生穩定的正現金流，第二季度自由現金流為 4.16 億美元。

And finally, now let me turn to our financial guidance for full year 2023. The business remains on track with our forecast for the full year. And today, we are reaffirming our full year guidance of 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 and you can refer to our press release for other important guidance assumptions.

最後，現在讓我談談我們 2023 年全年的財務指引。該業務仍符合我們對全年的預測。今天，我們重申我們的全年指引，即與 2022 年報告的結果相比，2023 年全年收入下降幅度在中個位數百分比範圍內。 2023 年全年非 GAAP 攤薄每股收益在 15 美元至 16 美元之間，您可以參閱我們的新聞稿以了解其他重要的指導假設。

So now I'll turn it back over to Chris for a few closing comments.

現在我將把它轉回給克里斯，讓他做一些總結評論。

Thank you, Mike. Well, in addition to reengineering our cost base, we're actually also reengineering the marketed portfolio of products. We've already had 2 approvals this year of QALSODY and LEQEMBI in the United States. As we look forward for the rest of the year and into early next year, we have a number of other important milestones for our portfolio. We are expecting a decision by the PMDA in Japan in the third quarter, by the EMA in Europe in the first quarter of next year and in the first quarter of next year also in China. We also are expecting a decision by the FDA on Zuranolone actually next week potentially. And then we also are continuing to evolve LEQEMBI. As Priya said, we are expecting to be able to submit the regulatory dossiers for LEQEMBI subcu in Q1 of next year and also a regulatory filing for maintenance dosing next year.

謝謝你，邁克。嗯，除了重新設計我們的成本基礎之外，我們實際上還在重新設計營銷的產品組合。今年我們已經在美國獲得了 2 個 QALSODY 和 LEQEMBI 的批准。當我們展望今年剩餘時間和明年初時，我們的投資組合還有許多其他重要的里程碑。我們預計日本 PMDA 將在第三季度做出決定，歐洲 EMA 將在明年第一季度做出決定，中國也將在明年第一季度做出決定。我們還預計 FDA 可能會在下週就 Zuranolone 做出決定。然後我們還在繼續發展 LEQEMBI。正如 Priya 所說，我們預計能夠在明年第一季度提交 LEQEMBI subcu 的監管檔案，以及明年維持劑量的監管備案。

So in addition to that, with the new product approvals that are expected, we're going to continue, obviously, to look through our external growth opportunities. As I have said before, this is an opportunity to expand the portfolio more into rare diseases, into immunology and neuropsychiatry.

因此除此之外，隨著新產品的預期批准，我們顯然將繼續尋找外部增長機會。正如我之前所說，這是將產品組合更多地擴展到罕見疾病、免疫學和神經精神病學領域的機會。

So with that, Chuck, we'll turn it back and invite questions.

因此，查克，我們將轉回並邀請提問。

Thanks, Chris. Operator, can we please poll for questions?

謝謝，克里斯。接線員，我們可以投票詢問問題嗎？

(Operator Instructions) Your first question comes from the line of Brian Abrahams with RBC Capital Markets.

（操作員說明）您的第一個問題來自 RBC Capital Markets 的 Brian Abrahams。

Congrats on all the developments. So we recently saw some competitor data at a medical conference. And I guess I'm curious, as you've seen things evolve here, what are the most important learnings that you've been taking away on the overall beta amyloid class efficacy and safety profiles? And can you maybe expand a little bit more on your latest views on how you expect the competitive dynamics to play out in the space and the impact to your overall launch strategy?

祝賀所有的進展。所以我們最近在一次醫學會議上看到了一些競爭對手的數據。我想我很好奇，正如您所看到的事情的發展，您在 β 澱粉樣蛋白類的整體功效和安全性方面學到的最重要的知識是什麼？您能否進一步闡述一下您對這一領域競爭動態的預期以及對您整體發布策略的影響的最新看法？

Thanks for the question, Brian. This is going to be super interesting from a commercial point of view because there are an awful lot of different factors at play here. I think as I said, the markets are sort of thinking there's 2 A-beta antibodies here, and they remove plaque and that's it. And the story is actually a whole lot more complex.

謝謝你的提問，布萊恩。從商業角度來看，這將非常有趣，因為這裡有很多不同的因素在起作用。我認為正如我所說，市場認為這裡有 2 種 A-β 抗體，它們可以去除牙菌斑，僅此而已。這個故事實際上要復雜得多。

First, I would say these are 2 products with -- that really go after the problem in a different way. And I think one of the most interesting things that's going to come out of this are the soluble protofibrils. These are the most neurotoxic forms of A-beta. And lecanemab goes after those whereas donanemab doesn't. And these are the soluble forms. And I think that will actually play a factor in our view, which is that this is going to be more of a chronic disease that you can remove the plaque, but the soluble forms and this is judged by what we're seeing in some of the biomarkers could actually still continue to play a role, which is why our belief is that we will need maintenance therapy over time.

首先，我想說，這兩種產品確實以不同的方式解決了問題。我認為最有趣的事情之一就是可溶性原纖維。這些是 A-β 最具神經毒性的形式。 lecanemab 致力於解決這些問題，而 donanemab 則不然。這些是可溶形式。我認為這實際上會在我們的觀點中發揮一個因素，那就是這將更多地是一種慢性疾病，你可以去除斑塊，但可溶性形式，這是根據我們在一些病例中看到的情況來判斷的生物標誌物實際上仍然可以繼續發揮作用，這就是為什麼我們相信隨著時間的推移我們將需要維持治療。

But there's also a difference in how these patients were studied. First, much different patient populations. Lecanemab was studied actually in an earlier patient population, roughly 2/3 were in MCI and 1/3 in mild. And donanemab was the reverse. And this is important because there's different rates of progression amongst these patients. And so actually -- and when Priya talked about these low tau, which have no overlap with the low tau -- low to medium tau that donanemab study, these are patients that would really progress quite slowly. So to actually see an effect like that, I think, really speaks to the efficacy of this product.

但這些患者的研究方式也存在差異。首先，患者群體差異很大。 Lecanemab 實際上是在早期患者群體中進行研究的，大約 2/3 為 MCI，1/3 為輕度。而多納奈單抗則相反。這很重要，因為這些患者的進展速度不同。因此，實際上，當 Priya 談到這些低 tau 蛋白（與多南單抗研究中的低至中 tau 蛋白沒有重疊）時，這些患者的進展確實會相當緩慢。因此，我認為，實際看到這樣的效果確實說明了該產品的功效。

Then there's also all the different end points. Lilly measured their primary endpoint on a Lilly designed end point. Lecanemab used the gold standard, which is the CDR-Sum of Boxes. But when you start looking at activities of daily life, you start to see differences and there are some other markers where we think we can demonstrate where efficacy is going to be. And then, of course, safety will be a big issue. When the most neurologists, if they've seen ARIA before, it's been pretty rare. I mean we do know that ARIA can occur even in the placebo group, but it's not something that'll have seen very often. And so this is going to be a different thing for them first to think about monitoring for safety with the MRIs. But it's one thing to be at a conference and look at safety from a data point of view. It's another thing I think to actually be looking at MRIs and seeing ARIA. And I think the safety benefit of lecanemab will be quite important to physicians as we go forward.

然後還有所有不同的終點。禮來公司在禮來公司設計的終點上測量了他們的主要終點。 Lecanemab 使用黃金標準，即 CDR-Sum of Boxes。但是，當您開始觀察日常生活活動時，您開始看到差異，並且還有一些其他標記，我們認為我們可以證明功效將在哪裡。當然，安全將是一個大問題。對於大多數神經科醫生來說，如果他們以前見過 ARIA，那是相當罕見的。我的意思是，我們確實知道 ARIA 即使在安慰劑組中也可能發生，但這並不是經常看到的情況。因此，對於他們來說，首先考慮使用 MRI 進行安全監測將是另一回事。但參加會議並從數據的角度看待安全是一回事。我認為實際觀察 MRI 和 ARIA 是另一回事。我認為隨著我們的前進，lecanemab 的安全益處對醫生來說非常重要。

So there are a number of dimensions here that I think will be developed over time. There's going to be all the different blood diagnostics that come along. Personally, my belief is that we're going to be seeing treatment progressively over the years in earlier patients before too much neuronal death has occurred. And of course, that's where LEQEMBI's benefit will arise where they have already studied much more of these patients. Generally, I would say Lilly has been focused on looking at subpopulations and trying to say, okay, in this subpopulation, we've got this result, in that subpopulation. But when physicians are dealing with patients in their practice, they don't want to deal with the subpopulation. They want to have a medicine that actually has broad coverage. And I think that's where LEQEMBI will also demonstrate its benefits.

因此，我認為這裡有許多維度將隨著時間的推移而發展。將會出現各種不同的血液診斷。就我個人而言，我相信，在發生過多的神經元死亡之前，我們將在未來幾年內逐步對早期患者進行治療。當然，這就是 LEQEMBI 的優勢所在，因為他們已經對這些患者進行了更多研究。一般來說，我想說禮來公司一直專注於研究亞群，並試圖說，好吧，在這個亞群中，我們在那個亞群中得到了這個結果。但當醫生在實踐中與患者打交道時，他們不想與亞人群打交道。他們想要一種實際上具有廣泛覆蓋範圍的藥物。我認為 LEQEMBI 也將在這裡展示其優勢。

So it's going to be quite interesting. There's lots of data here to pour over that's come out of the AAIC and a lot of that will just become much more tangible over the coming months and years.

所以這將會非常有趣。這裡有大量來自 AAIC 的數據可供參考，其中很多數據將在未來幾個月和幾年內變得更加切實。

Our next question comes from the line of Marc Goodman with Leerink Partners.

我們的下一個問題來自 Marc Goodman 和 Leerink Partners。

Mike, just to make sure we're all aligned here with the numbers and the cost savings. So OpEx, $4.5 billion for 2023. So we should be thinking $3.8 billion in 2025? And then how do we get there with respect to SG&A and R&D? Is this -- are they about even? I mean, is R&D going to move below the $2 billion line? Just help us give us a sense of that and maybe just as you talk about the P&L. Just comment on -- do you expect gross margins to be higher or lower in kind of those years? Just to help us think about how the P&L is going to look?

邁克，只是為了確保我們都與數字和成本節省保持一致。那麼，2023 年運營支出為 45 億美元。那麼我們應該考慮 2025 年為 38 億美元？那麼我們如何在銷售、行政管理和研發方面實現這一目標呢？這是——他們差不多嗎？我的意思是，研發費用會低於 20 億美元嗎？請幫助我們了解這一點，也許就像您談論損益表一樣。只是評論一下——您預計那些年的毛利率會更高還是更低？只是為了幫助我們思考損益表會是什麼樣子？

Yes, Marc, thanks for the question. So your math is correct. Our goal would be to achieve a full run rate of the $700 million net savings in 2025. So on an OpEx base of $4.5 billion, that would take it to the neighborhood of about $3.8 billion. The savings will be both in SG&A and R&D. We've already done quite a bit in R&D, as we talked about, that will yield a lot of savings with our prioritization program, but we'll also be looking at ways of conducting our clinical trials, our existing trials more efficiently.

是的，馬克，謝謝你的提問。所以你的數學是正確的。我們的目標是在 2025 年實現 7 億美元淨節省的全部運行率。因此，在 45 億美元的運營支出基礎上，這將使其達到約 38 億美元。節省的資金將用於銷售、行政管理和研發。正如我們所談到的，我們已經在研發方面做了相當多的工作，這將通過我們的優先計劃節省大量成本，但我們也會尋找更有效地進行臨床試驗和現有試驗的方法。

So the overall savings will be a mix. We're not providing full granularity on whether R&D will be plus or minus the $2 billion number that you threw out, but I would estimate that the savings from here would be probably a little more weighted to the SG&A line and a little less to R&D, but ultimately, the savings will come from both sides.

因此，總體節省將是一個混合。我們沒有提供關於研發是否會加上或減去您拋出的 20 億美元數字的完整詳細信息，但我估計，這裡節省的費用可能會更多地分配給 SG&A 線，而更少地分配給研發，但最終，節省的資金將來自雙方。

The gross margin, that's a trend that we expect will continue at least for the near term. And when you look at the product mix, we obviously have the continuing declines in the -- some of the MS products, which are on the higher margin side and then you have contract manufacturing that's really growing quite a bit year-on-year. So we do expect to see our cost of sales as a percentage of revenue, at least for the near term to be a bit lower than what we've -- or I should say, the cost of sales percentage would be higher, the gross margin would be lower than what we've seen in the past.

毛利率是我們預計至少在短期內將持續的趨勢。當你看看產品組合時，我們顯然會看到一些 MS 產品持續下降，這些產品的利潤率較高，然後你的合同製造確實同比增長了不少。因此，我們確實希望看到我們的銷售成本佔收入的百分比，至少在短期內會比我們現在的水平略低——或者我應該說，銷售成本百分比會更高，總收入利潤率將低於我們過去看到的水平。

And then over time, as LEQEMBI becomes profitable and ramps up, we should hopefully see some recovery up on the gross margin line.

然後隨著時間的推移，隨著 LEQEMBI 開始盈利並實現增長，我們應該有望看到毛利率有所回升。

Our next question comes from the line of Robyn Karnauskas with Truist.

我們的下一個問題來自羅賓·卡瑙斯卡斯 (Robyn Karnauskas) 與 Truist 的對話。

I guess -- I would just be curious, initially, as you're talking to doctors about if there's a difference between the academic and the community setting and interest in using drug and coordinating that. Can you give us more details as to how laborious and how easy the CMS registry now that it's up and running is and what questions they're asking?

我想——一開始我只是好奇，當你和醫生談論學術和社區環境以及對使用藥物和協調的興趣之間是否存在差異時。您能否向我們提供更多詳細信息，說明 CMS 註冊中心啟動並運行後是多麼費力和容易，以及他們提出了哪些問題？

I think first on the registry, all the feedback is this is manageable. I think everybody would prefer not to have a registry, but personally been on it, there's drop-down menus. Most of the data are available from the medical record. So we think that, that part should be okay.

我認為首先在註冊表上，所有反饋都是這是可以管理的。我認為每個人都不願意有註冊表，但就個人而言，有下拉菜單。大多數數據可以從病歷中獲得。所以我們認為這部分應該沒問題。

There's some bumpiness around the PET scan reimbursement that should be clarified in the next 90 days. But I think where we are now, the one PET scan that is included should not be a barrier. I think there's just -- the mechanics actually of seeing patients that will change. There's going to be a need to do more of the cognitive testing, getting the PET scan or the lumbar puncture, figuring out where to go with the infusion centers and then getting the MRIs. There will be a routine that will develop in offices. But to start with, nobody is doing that right now, really. I mean, we obviously have some centers that have been able to start infusing LEQEMBI during the period before full traditional approval. But if we look at the masses, everybody is having to gear up for this.

PET 掃描報銷存在一些障礙，應該在未來 90 天內得到澄清。但我認為我們現在所處的位置，所包含的一次 PET 掃描不應成為障礙。我認為看病人的實際機制將會改變。需要進行更多的認知測試，進行 PET 掃描或腰椎穿刺，確定輸液中心的位置，然後進行 MRI 檢查。辦公室裡將會有一個慣例。但首先，現在確實沒有人這樣做。我的意思是，我們顯然有一些中心能夠在完全傳統批准之前開始注入 LEQEMBI。但如果我們看看大眾，每個人都必須為此做好準備。

I think one of the other things that I would say is there's been so much disappointment in this field over the years. A lot of hope, but a lot of these medicines didn't play out. And so I think there's been an awful lot of wait and see amongst the some of the medical community, are we really going to get full approval? Are we really going to get CMS approval?

我想我要說的另一件事是，多年來這個領域有很多令人失望的事情。人們滿懷希望，但很多藥物並沒有發揮作用。所以我認為醫學界的一些人一直在觀望，我們真的會得到完全批准嗎？我們真的會獲得 CMS 批准嗎？

So I think now that is in place, which is, as I said before, I think is a really seminal moment in health care. We'll see the practicality for this. And we've always said that this is going to be a relatively measured uptake on revenue. I will say that the whole field organization is geared up for this. This is a much more complex field organization than what you would have with a typical launch with the care navigators, with MSLs, with field reps, with regional thought leader professionals. So there are going to be a lot of people actually holding hands with patients, with physician practices, trying to help make sure that this is as seamless as possible. And -- but it is not clearly as simple as just prescribing a pill and going down to your local pharmacy.

所以我認為現在已經到位，正如我之前所說，我認為這是醫療保健領域真正具有開創性的時刻。我們將看到它的實用性。我們一直說，這將是一個相對謹慎的收入增長。我想說的是，整個現場組織都為此做好了準備。這是一個比典型的由護理導航員、MSL、現場代表和區域思想領袖專業人員啟動的現場組織要復雜得多。因此，實際上將會有很多人與患者攜手並進，通過醫生的實踐，試圖幫助確保這一過程盡可能順利。而且——但這顯然並不像開藥方然後去當地藥房那麼簡單。

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

你的下一個問題來自富國銀行的 Mohit Bansal。

And maybe a question for Priya. So when you think about subcutaneous LEQEMBI, and you see the data later this year. But how do you think about positioning it? Is it -- do you think it is more of a maintenance treatment after the IV LEQEMBI versus an induction kind of treatment? And how important is Cmax to get an induction approval here? Super helpful, thank you.

也許還有一個問題要問 Priya。因此，當您考慮皮下 LEQEMBI 時，您會看到今年晚些時候的數據。但您如何看待它的定位呢？您是否認為這更像是 IV LEQEMBI 後的維持治療而不是誘導治療？ Cmax 在這裡獲得入職批准有多重要？超級有幫助，謝謝。

Thank you, Mohit. So it's a great question. I think maybe before I answer that, I'll just say that Biogen and Eisai are really looking to simplify and improve the patient journey and this is a multipronged effort. One is subcutaneous formulation, which can address the infusion capacity and other issues with potential for an auto-injector and self-administration at home. And then the second is really thinking about how LEQEMBI can be positioned to really address the long-term duration question that is still out there. The good news here is that LEQEMBI does have the opportunity to be treated -- to be used with a long duration. And the question is, what is the right maintenance duration for this therapy?

謝謝你，莫希特。所以這是一個很好的問題。我想也許在回答這個問題之前，我只想說百健（Biogen）和衛材（Eisai）確實希望簡化和改善患者的治療過程，這是一項多管齊下的努力。一種是皮下製劑，它可以解決輸注能力和其他可能在家中使用自動注射器和自我給藥的問題。第二個是真正思考 LEQEMBI 如何定位才能真正解決仍然存在的長期持續時間問題。好消息是 LEQEMBI 確實有機會得到治療——長期使用。問題是，這種療法的正確維持時間是多長？

And with regards to subcutaneous, the data that we just presented at AAIC was modeling data to show that really the subcutaneous formulation would be about 720 milligrams administered weekly instead of the intravenous biweekly therapy. Now the important thing here to understand is that really, it is the hope and the data kind of point to the fact that safety could actually be better with the subcutaneous formulation. So we might have lower rates for ARIA. And the filing is expected to be complete by Q1 2024. I also expect that more data, Eisai has communicated this will be released at CTAD this year.

至於皮下注射，我們剛剛在 AAIC 上提供的數據是模型數據，表明皮下注射製劑實際上每週給藥約 720 毫克，而不是每兩周靜脈注射治療。現在要理解的重要一點是，實際上，希望和數據表明皮下製劑的安全性實際上可以更好。因此，我們可能會降低 ARIA 的費率。備案預計將於 2024 年第一季度完成。我還預計衛材已表示將在今年的 CTAD 上發布更多數據。

So I think let's wait for more of that data, which is, I think, forthcoming, and we look forward to the -- hopefully, simplifying the patient journey.

因此，我認為讓我們等待更多的數據，我認為這些數據即將發布，我們期待 - 希望能夠簡化患者的旅程。

Next is Umer Raffat with Evercore.

接下來是 Umer Raffat 和 Evercore。

I feel like there's an elephant in the room, and I do think we should speak to it. And Chris, this one is for you specifically. And the question really is, investors are very curious what was your thought process on 2 specific occasions in the last few weeks? First, when you were first told about the proposed changes to the Board, what was your thought process? And second, what was your thought process in deciding whether or not you needed to put out any disclosures?

我覺得房間裡有一頭大象，我確實認為我們應該和它談談。克里斯，這個是專門為你準備的。問題確實是，投資者很好奇你在過去幾週的兩個特定場合的思考過程是什麼？首先，當您第一次得知董事會的擬議變動時，您的思考過程是什麼？其次，您在決定是否需要披露任何信息時的思考過程是什麼？

So I think if we just step back, I mean there's -- clearly, a lot of people got focused on some of the gossip here. But I think more fundamentally, there's been a significant change with our Board. And anybody who knows anything about Boards is that you only make significant changes to the Board through a consensus of the Board. Now, Board is a college of peers with equal power. And there had been a lot of significant investor outreach. The company is doing an awful lot of change internally at a management level, addressing a lot of the concerns that investors, I think, have been raising for quite a number of years and certainly concerns that I have heard. And the Board actually said, well, we need to think about the governance and are we changing as well.

所以我認為，如果我們退後一步，我的意思是，顯然，很多人都關注這裡的一些八卦。但我認為更根本的是，我們的董事會發生了重大變化。任何對董事會有所了解的人都會知道，只有在董事會達成共識的情況下，才能對董事會做出重大改變。現在，董事會是一個擁有平等權力的同儕學院。並且還進行了很多重要的投資者宣傳活動。該公司正在管理層內部進行大量變革，解決了投資者多年來一直提出的許多擔憂，當然也是我聽到的擔憂。董事會實際上說，我們需要考慮治理以及我們是否也需要改變。

And I can tell you that all of the discussion to which I was a party, all concerned one thing, and that is what is right for Biogen. And I found that very encouraging. But we have a new chair and I have to say I couldn't be happier working with Caroline. She's someone of unimpeachable integrity, extremely smart, analytical but really has a real passion for the mission of the company. And I think the Board is clearly foursquare behind all of the changes that we're making. So I think all of that is good.

我可以告訴你，我參與的所有討論都涉及一件事，這就是百健 (Biogen) 的正確選擇。我發現這非常令人鼓舞。但我們有一把新椅子，我不得不說，與卡羅琳一起工作我感到非常高興。她是一個無可挑剔的正直人，非常聰明，善於分析，但對公司的使命充滿熱情。我認為董事會顯然是我們正在做出的所有變革的堅定支持者。所以我認為這一切都很好。

In terms of disclosure, we look at people. We don't look at their personal relationships. And I would just say that Glass Lewis and ISS recommended Susan Langer and investors voted or under the Board, and I don't think there's really anything more to be -- that needs to be said about that.

在披露方面，我們關注的是人。我們不看他們的私人關係。我只想說，格拉斯·劉易斯和 ISS 推薦了蘇珊·蘭格，投資者投票或在董事會下投票，我認為真的沒有什麼可說的了——對此需要多說。

We have a question from Salveen Richter with Goldman Sachs.

我們有高盛 Salveen Richter 提出的問題。

How is the Fit for Growth in your cost alignment work influenced your thoughts on M&A and BD? And you've noted the 3 disease areas, but can you just provide some thoughts on the value proposition across the areas? Any limits with regard to size of the deal and the use of equity?

您的成本調整工作中的“適合增長”是如何影響您對併購和業務拓展的想法的？您已經註意到了 3 個疾病領域，但您能否就這些領域的價值主張提供一些想法？交易規模和股權使用有什麼限制嗎？

Fit for Growth, remember, is really reflecting the transition of the company. We have been very focused on multiple sclerosis over 45 years. We had some very prosperous times in the more recent history of the company. And as we have seen a reversal of fortunes in some of those products, I don't think we, as a company, have really made the changes in our organizational structure and our cost base to really reflect that transition.

請記住，適合增長確實反映了公司的轉型。 45 年來，我們一直非常關注多發性硬化症。在公司最近的歷史中，我們經歷過一些非常繁榮的時期。正如我們看到其中一些產品的命運逆轉一樣，我認為作為一家公司，我們並沒有真正對我們的組織結構和成本基礎做出改變來真正反映這種轉變。

One of the things I'd like to tell our management teams is that the hardest word in management is And. You have to think about the short term and the long term. But one of the things is you have to be cost efficient and you have to invest for growth. And that's been a very tricky exercise. We didn't have all the product launches, just cost reduction would be fairly easy. What we've had to do is be a lot more thoughtful about what is the best way to position Biogen going forward? And that's why we didn't start with where we were, but we started with where we want to be. What is that organization? How many people? We benchmarked the organization.

我想告訴我們的管理團隊的一件事是，管理中最難的詞是“和”。你必須考慮短期和長期。但其中一件事是你必須具有成本效益，並且必須為增長進行投資。這是一個非常棘手的練習。我們沒有推出所有產品，只是降低成本相當容易。我們必須做的是更加深思熟慮地思考什麼是百健（Biogen）未來定位的最佳方式？這就是為什麼我們不是從我們現在的位置開始，而是從我們想要達到的目標開始。那個組織是什麼？多少人？我們對組織進行了基準測試。

We've looked at the -- making sure we have enough investment in the product launches, have enough investment in those exciting R&D projects that we would want to focus on and then work backwards from there. So I think the company is well positioned now to be oriented towards growth while also managing our historic portfolio. And again, I come back and saying we are still the market leaders in MS, and we have an obligation to both physicians and their patients on that. And so we will be changing the way we -- the promotional mix, but we're not going to just walk away from that either.

我們已經研究過——確保我們對產品發布有足夠的投資，對那些我們想要關注的令人興奮的研發項目有足夠的投資，然後從那裡開始向後工作。因此，我認為該公司現在處於有利位置，可以面向增長，同時管理我們的歷史投資組合。我再說一遍，我們仍然是多發性硬化症的市場領導者，我們對醫生和患者都有義務。因此，我們將改變促銷組合的方式，但我們也不會放棄這一點。

And I think in terms of M&A and external growth, is really what do we do to build on that? And that starts with BD at an earlier stage of the pipeline. Are there things that we want to build on to that? And in particular, as I've said in the past, I think -- we're proud of our position in neuroscience. The neurological conditions are slow progressing diseases and really require very expensive long trials. And they are ones where you can't really derisk them with a Phase II asset. So we're not going to walk away by any means, but we do need to get into portfolio decisions where we can actually get a better read on efficacy and safety in Phase II and I think we can do that with the rare diseases with more of a focus on immunology. If you know -- we've never been far from immunology in the history of the company. And of course, with -- we already are into our psychiatry and can we build that portfolio. But I think we have now a much more nimble structure, a more empowered organization. One of the things that comes out of our culture surveys is that we can take quite a long time to make a decision.

我認為就併購和外部增長而言，我們真的要在此基礎上做些什麼嗎？這從管道早期階段的 BD 開始。我們是否想在此基礎上發展一些東西？特別是，正如我過去所說，我認為——我們對我們在神經科學領域的地位感到自豪。神經系統疾病是進展緩慢的疾病，確實需要非常昂貴的長期試驗。而且你無法用第二階段的資產真正消除它們的風險。因此，我們不會以任何方式放棄，但我們確實需要進行投資組合決策，這樣我們實際上可以更好地了解第二階段的療效和安全性，我認為我們可以用更多的藥物來治療罕見疾病重點關注免疫學。如果你知道的話——在公司的歷史上，我們從未遠離過免疫學。當然，我們已經進入了精神病學領域，我們可以建立這個投資組合嗎？但我認為我們現在擁有更加靈活的結構、更加強大的組織。我們的文化調查得出的結論之一是我們可能需要很長時間才能做出決定。

So in all of those things, when you're dealing with partners and you're dealing with business development, if you want to have that (inaudible) that -- ability to be agile. And so I think Fit for Growth will actually facilitate that. But really, the approach to external growth is more strategic in how we shape the portfolio of the company.

因此，在所有這些事情中，當您與合作夥伴打交道並處理業務開發時，如果您想擁有（聽不清）敏捷的能力。因此，我認為“適合增長”實際上會促進這一點。但實際上，外部增長的方法在我們如何塑造公司的投資組合方面更具戰略意義。

And that limits the size or use of equity? It's part of the question, Chris.

這限制了股權的規模或用途嗎？這是問題的一部分，克里斯。

I think we're really looking at what really makes sense for the company. I don't think we've seen anything that would require use of equity. And Mike, we've got, I think, about $7.3 billion in cash. So as far as I'm concerned, we don't -- everything that we think, we can manage with what we've got.

我認為我們真正在尋找對公司真正有意義的東西。我認為我們還沒有看到任何需要使用股權的事情。邁克，我認為我們擁有大約 73 億美元的現金。因此，就我而言，我們不會——我們認為的一切，我們都可以用我們所擁有的來管理。

The most important thing is to really -- one of the major things we try to do with Fit for Growth is really get a lot more rigorous about how we allocate capital. We've had this very good fortune over the last few years. And when there's a lot of money in the company, don't have the same rigor about how you allocate capital. That is a real focus for us. We really want to make sure that we're putting our investments in the things that make the best returns for the company and our shareholders. And so that part is a cultural shift that's coming out of that, and I think that will affect how we think about business development as well.

最重要的是，我們在“適應增長”計劃中嘗試做的主要事情之一就是更加嚴格地分配資本。過去幾年我們的運氣非常好。當公司有很多錢時，就不必對如何分配資本有同樣嚴格的要求。這是我們真正關注的焦點。我們確實希望確保我們的投資能夠為公司和股東帶來最佳回報。因此，這部分是由此產生的文化轉變，我認為這也會影響我們對業務發展的看法。

We'll go next to Michael Yee with Jefferies.

接下來我們將與 Jefferies 一起前往 Michael Yee。

Just wanted to ask on the Zuranolone program. Obviously, you have PDUFA date coming up. But Chris, you've made some pretty bullish comments on this before. Maybe rightsize your expectations about how to think about that opportunity and whether there could be a split label? And importantly, since you're talking about cost cutting, how a positive approval or maybe some various form of 2 different indications could impact expenses going forward? So just talk a little bit about Zuranolone.

只是想詢問 Zuranolone 計劃。顯然，PDUFA 日期即將到來。但是克里斯，你之前對此發表過一些非常樂觀的評論。也許可以調整您對如何考慮這個機會以及是否可以拆分標籤的期望？重要的是，既然您談論的是成本削減，那麼積極的批准或兩種不同跡象的某種不同形式可能會如何影響未來的支出？那麼就簡單談談 Zuranolone 吧。

Yes. Well, we have a PDUFA date on August 5. So we'll be able to give you a full update once we've had the FDA decision. So I don't really want to talk about that process right now.

是的。嗯，我們的 PDUFA 日期是 8 月 5 日。因此，一旦 FDA 做出決定，我們將能夠為您提供完整的更新。所以我現在不想談論這個過程。

I'll just say there is an enormous unmet need in [mental health]. And that only seems to be rising. You can't look at the news without reading about reports of the rise of mental health conditions. I think that partly got exacerbated by the pandemic. And one of the things is that, that affects that the pandemic did was I think really bring this more out into the open where it belongs. Certainly, PPD is a huge unmet need, massive taboo around that. And that will be quite a heavy lift actually because it's not really -- there isn't really a clarity around who really is responsible for diagnosing and treating mothers at that point. And so we look forward to being able to hopefully contribute to that.

我只想說，[心理健康]方面存在巨大的未滿足需求。而且這個數字似乎還在上升。你不可能在看新聞時不閱讀有關心理健康狀況上升的報導。我認為這種情況在一定程度上因大流行而加劇。其中一件事是，大流行造成的影響是我認為真正將其更多地公開化。當然，產後抑鬱症是一個巨大的未滿足的需求，也是一個巨大的禁忌。實際上，這將是一個相當沉重的負擔，因為當時並沒有真正明確誰真正負責診斷和治療母親。因此，我們期待能夠為此做出貢獻。

But there is a significant unmet need also in the way it's treated. I think something that could act much faster than current treatments, something that's perhaps episodic, could be a great value to patients. So I do think there is an opportunity. But again, we need to wait for the FDA decision, and we'll fully update everybody at that point.

但在治療方式上也存在重大未滿足的需求。我認為一些比目前的治療方法起效更快的方法，可能是間歇性的，對患者來說可能具有很大的價值。所以我認為確實有機會。但同樣，我們需要等待 FDA 的決定，屆時我們將向所有人全面通報最新情況。

Our next question comes from Tim Anderson with Wolfe Research.

我們的下一個問題來自沃爾夫研究公司的蒂姆·安德森。

I know that Biogen and Eisai continue to talk up the need to dose Alzheimer's drugs or LEQEMBI specifically chronically and not just for a finite period and you're talking about protofibrils and how they're the most neurotoxic species and that sort of thing. From what I understand, the science is really thin that says you need to dose chronically and the soluble forms of A-beta really make a difference in terms of continued disease progression. And empirically, if we just look at what came out of AAIC, we see a similar level of reduction and improvement in cognition with finite dosing with donanemab and we see continued curve separation with Lilly's product and your product. So doesn't that potentially call in the question the need for chronic dosing? And isn't that possibly a risk with LEQEMBI that docs actually only use it until plaque is cleared and then they stop, which would lead to a very different revenue opportunity for LEQEMBI?

我知道百健（Biogen）和衛材（Eisai）繼續談論需要長期服用阿爾茨海默氏症藥物或 LEQEMBI，而不僅僅是在有限的時間內服用，你們談論的是原纖維以及它們如何成為最具神經毒性的物種等等。據我了解，科學表明您需要長期服用藥物，而且可溶形式的 A-β 確實對疾病的持續進展產生影響，這一點確實很薄弱。從經驗上看，如果我們只看 AAIC 的結果，我們會發現有限劑量的多南單抗在認知方面有類似水平的降低和改善，並且我們看到禮來公司的產品和你們的產品的曲線持續分離。那麼這是否可能會引發一個問題：是否需要長期給藥？難道 LEQEMBI 可能存在風險嗎？醫生實際上只使用它，直到牙菌斑被清除，然後停止使用，這將為 LEQEMBI 帶來非常不同的收入機會？

Thank you for the question. Yes. So this is a very important area of query and scientific hypothesis. So maybe before I really talk about LEQEMBI or donanemab, we can agree that Alzheimer's disease is really a progressive and eventually fatal condition with obviously neurodegeneration involved along the way.

感謝你的提問。是的。所以這是一個非常重要的詢問和科學假設領域。因此，也許在我真正談論 LEQEMBI 或 donanemab 之前，我們可以同意阿爾茨海默病確實是一種進行性並最終致命的疾病，在此過程中明顯涉及神經退行性變。

And what we've seen with LEQEMBI and actually multiple lines of evidence outside of LEQEMBI also with aducanumab in the past, is that when you clear plaque, it does not re-accumulate that easily. But what you do see is progression of disease and you see an impact on the fluid biomarkers. So with LEQEMBI and with the gap period that we had in Phase II, we saw an increasing -- a reversal of the A-beta 42:40 ratio, implying that disease continues to progress. We saw very similar evidence with aducanumab. And I think what we see now with the plasma p-tau levels, in the past, we saw with aducanumab sort of decreasing with the EMERGE data set. And with LEQEMBI, what we've seen with p-tau181 is a stabilization.

我們在 LEQEMBI 中看到的情況以及 LEQEMBI 之外的多線證據以及阿杜卡單抗過去的實際情況是，當您清除牙菌斑時，它不會輕易重新積累。但您確實看到的是疾病的進展，並且您看到了對液體生物標誌物的影響。因此，通過 LEQEMBI 以及我們在第二階段的間隙期，我們看到 A-β 42:40 比例出現逆轉，這意味著疾病繼續進展。我們在 aducanumab 方面看到了非常相似的證據。我認為我們現在看到的血漿 p-tau 水平，在過去，我們看到阿杜卡單抗隨著 EMERGE 數據集的增加而下降。通過 LEQEMBI，我們在 p-tau181 中看到了穩定性。

And actually, if you saw the donanemab data on p-217, which was the plasma tau biomarker they use, and these track really quite closely, is that you see a slight increase.

實際上，如果您看到 p-217（他們使用的血漿 tau 生物標記物）上的 donanemab 數據，並且這些跟踪非常接近，您會看到略有增加。

So I think we still need to understand with more data transparency, the donanemab data of what really happens to patients who stopped at 6 months or stopped at 1 year. And we hope we'll see more of that data from their open-label extension and be able to draw conclusion. But when you look at the substrate for donanemab, it really does not make sense to continue to dose, one, because of substrate exhaustion and two, because of the presence of antidrug antibodies, close to about 84% to 87%. Whereas with LEQEMBI, you have the opportunity to have an individualized treatment duration discussion between the patient and the doctor because actually, it continues to impact soluble substrate, as Chris mentioned, and we are going to be generating data to actually look at this in a very systematic way with the Phase II open-label extension.

因此，我認為我們仍然需要以更高的數據透明度來了解在 6 個月或 1 歲時停止治療的患者的真實情況的 donanemab 數據。我們希望我們能從他們的開放標籤擴展中看到更多數據並能夠得出結論。但當你觀察多南單抗的底物時，繼續給藥確實沒有意義，一是因為底物耗盡，二是因為抗藥物抗體的存在，接近約 84% 至 87%。而使用 LEQEMBI，您有機會在患者和醫生之間進行個性化的治療持續時間討論，因為實際上，正如克里斯提到的，它會繼續影響可溶性底物，我們將生成數據來實際研究這一點II 期開放標籤擴展的非常系統的方法。

So I think that the jury is out but the multiple lines of evidence do not seem to indicate that you can stop and reverse Alzheimer's disease. So that's where I'll leave it.

因此，我認為目前還沒有定論，但多重證據似乎並不表明你可以阻止和逆轉阿爾茨海默病。所以這就是我要離開的地方。

We'll go next to Evan Seigerman with BMO.

接下來我們將與 BMO 的 Evan Seigerman 進行交流。

So now that you've talked through some of the right size that you plan on doing and now you're focusing on BD on the back half of the year. Can you talk about how you think about the value that still exists for BD in the market today? And are you focused on really near-term revenue opportunities to grow the business or earlier-stage development items?

現在您已經討論了計劃要做的一些合適的規模，現在您將在下半年重點關注 BD。您能談談您如何看待 BD 在當今市場上仍然存在的價值嗎？您是否專注於真正的短期收入機會來發展業務或早期開發項目？

Well, it's quite interesting. You say today, when I talk to bankers, it's interesting. I think if you've got something that has really good data that there tends to be a price for that, and that price is more or less constant. I was asking bankers, do you think Merck would have had to pay even more for Prometheus, for instance, 2 -- 2 years ago when kind of the go-go days of biotech, and their view was no.

嗯，這很有趣。你說今天我和銀行家談話很有趣。我認為，如果你有一些擁有非常好的數據的東西，那麼往往會有一個價格，而且這個價格或多或少是恆定的。我問銀行家，你認為默克公司是否需要為普羅米修斯支付更多費用，例如，兩兩年前生物技術的繁榮時期，他們的觀點是否定的。

And so I think if you find quality assets out there and that really doesn't vary that much. What does vary is all the other stuff, right? We got a little bit more interest in more speculative things and that's what really sort of says, well, are things relatively expensive or not. And as a company, I think -- I always like to say, our investors (inaudible) to make them rich and not someone else's shareholders. So if you're going to do a deal, you have to make sure that there is value creation for Biogen and its shareholders. And that's a hard thing. And we all know that a lot of BD doesn't do that.

所以我認為，如果你發現那裡有優質資產，那其實差別不大。唯一不同的是所有其他的東西，對吧？我們對更具投機性的事物產生了更多的興趣，這實際上就是說，東西是否相對昂貴。作為一家公司，我認為——我總是喜歡說，是我們的投資者（聽不清）讓他們變得富有，而不是其他人的股東。因此，如果你要進行交易，你必須確保為百健（Biogen）及其股東創造價值。這是一件很難的事情。我們都知道很多 BD 並不這樣做。

The way I look at Biogen, we've had now the decision on LEQEMBI. We have a pending decision at the FDA for Zuranolone. We've got pending decisions for LEQEMBI around the [world]. If you look at Biogen over the next 2, 3 years, there's an opportunity for a return to growth over that time frame. I think we are making some bold moves here to address our cost base and really reposition our resources in the company. And we have, I think, some super interesting products in our research and development pipeline that Priya mentioned. So if you look at it, we already have a value creation story. So anything that we're going to do has to be accretive to that picture.

以我對百健（Biogen）的看法，我們現在已經做出了 LEQEMBI 的決定。我們正在等待 FDA 對 Zuranolone 的決定。我們對[世界]各地的 LEQEMBI 有待決定。如果你看看百健（Biogen）未來兩三年的情況，你會發現在這段時間內有機會恢復增長。我認為我們正在採取一些大膽的舉措來解決我們的成本基礎並真正重新配置我們在公司的資源。我認為，Priya 提到的我們的研發渠道中有一些超級有趣的產品。所以如果你看一下，我們已經有了一個價值創造的故事。因此，我們要做的任何事情都必須促進這幅圖畫的發展。

And you do have to go look, and you're going to have to go look at hundred things before you find something that really works, and that's what our teams are doing. The worst thing you can do is fall in love with something because then you lose your objectivity. I can tell you that we are laser focused on changing the trajectory of our share price. As I've heard from so many investors, our share price hasn't really moved in 10 years. So that's where we are focused on really driving -- being much more focused on shareholder value, and that means allocating capital in a way that's commensurate with that.

你確實必須去看看，在找到真正有效的東西之前，你必須去看看數百件事，而這就是我們團隊正在做的事情。你能做的最糟糕的事情就是愛上某件事，因為這樣你就失去了客觀性。我可以告訴你，我們正專注於改變我們股價的軌跡。正如我從很多投資者那裡聽到的那樣，我們的股價已經十年沒有真正變動過。因此，這就是我們真正關注的地方——更加關注股東價值，這意味著以與之相稱的方式分配資本。

The next question comes from Ami Fadia with Needham.

下一個問題來自 Ami Fadia 和 Needham。

Maybe a bit of a follow-up on the last topic. It sounds like -- in the context of the Fit for Growth initiative, does it mean that from a BD perspective, you're unlikely to do a deal that's a significant lift from an R&D perspective over the next couple of years? And also, if you could provide some color on how you anticipate gross margin to evolve between 2023 and 2025? That would be helpful.

也許是上一個主題的後續內容。聽起來——在“適合增長”計劃的背景下，這是否意味著從業務拓展的角度來看，您不太可能在未來幾年內達成一項對研發角度有重大提升的交易？另外，您是否可以提供一些關於您預計 2023 年至 2025 年毛利率將如何變化的信息？那會有幫助的。

I missed part of that sentence out, does that mean on the BD that we would not do something I couldn't -- I didn't. Could you repeat the question?

我漏掉了那句話的一部分，這是否意味著在 BD 上我們不會做我做不到的事情——我沒有。你能重複一下這個問題嗎？

Sure. Does it mean that you would not do a deal? Yes, that you would not do a deal that is a significant heavy lift from an R&D perspective over the next couple of years?

當然。這是否意味著您不會達成協議？是的，您不會在未來幾年內進行一項從研發角度來看意義重大的交易嗎？

Well, I think we have enough heavy lifting from R&D to be honest. So I'm certainly looking at things that I think -- to me, it's less around the expenditure as how much risk you're taking. What I find hard is when we have a multiyear, 5-year type Phase III study that's essentially a proof of concept. That's, I think, what we're really trying to move away from.

嗯，說實話，我認為我們在研發方面的工作量已經夠大了。所以我當然會考慮我認為的事情——對我來說，支出的問題不在於你承擔了多少風險。我發現困難的是，我們進行了一項為期多年、為期 5 年的 III 期研究，這本質上是一個概念驗證。我認為這才是我們真正想要擺脫的。

Now what I would say though is we are clearly benchmarking. And I really want us to be rigorous on G&A. I want us to be competitive on the sales and marketing. On R&D, I want us to be super disciplined on capital. But I would say all the benchmarking we've done is that Biogen has actually been better than average on productivity. And I do believe greatly in a lot of the capability within Biogen. And so I do think if there are things that really make sense, I actually have higher degree of trust in our R&D organization that -- I think that we should continue to invest in R&D.

現在我要說的是，我們顯然正在進行基準測試。我真的希望我們能夠嚴格管理一般行政費用。我希望我們在銷售和營銷方面具有競爭力。在研發方面，我希望我們對資本非常嚴格。但我想說的是，我們所做的所有基準測試表明百健（Biogen）在生產力方面實際上優於平均水平。我確實非常相信百健（Biogen）公司的很多能力。所以我確實認為，如果有一些事情確實有意義，我實際上對我們的研發組織有更高程度的信任——我認為我們應該繼續投資於研發。

The really important thing is that you really -- the secret about R&D is you have to design a killer experiment, define what the criteria are for moving into the next stage and don't allocate capital unless you really meet those data. The problem in a lot of organizations is we fall in love with something. The data aren't quite clear, but we'll go and keep going because we have it. And I think the discipline to kill stuff that doesn't meet its milestones is something that is probably more important than anything else to managing R&D investments. And that's why I'm grateful to have Priya because I think Priya is extremely objective on this. We all are.

真正重要的是，研發的秘訣在於，你必須設計一個殺手級實驗，定義進入下一階段的標準，除非你真正滿足這些數據，否則不要分配資金。許多組織的問題是我們愛上了某些東西。數據還不太清楚，但我們會繼續前進，因為我們有數據。我認為，對於管理研發投資來說，淘汰那些不符合其里程碑的東西的紀律可能比其他任何事情都更重要。這就是為什麼我很感激 Priya，因為我認為 Priya 在這方面非常客觀。我們都是。

But again, I do think that we are an innovative company. And I wouldn't want to restrict too much Biogen's ability to invest in R&D over time but we're going to be extremely tough on what it is that we're going to choose to develop.

但我再次強調，我們是一家創新型公司。我不想過多地限制百健（Biogen）隨著時間的推移投資於研發的能力，但我們將對我們選擇開發的產品採取極其嚴格的態度。

And then maybe, Ami, on the gross margin line in terms of how we expect that to evolve, we said in our prepared remarks that we do expect to see our cost of sales as a percentage of revenue to continue to increase throughout the rest of 2023, and that's pretty heavily tied to the outsized contract manufacturing revenue that we're seeing this year. And without guiding beyond 2023, I can just say, trend-wise, when you look at some of our bigger ticket items, we've got the anti-CD20s, which are highly profitable. They're kind of flat to somewhat declining, has kind of been the trend there. You've got TECFIDERA, where you've got generic competition in the U.S. Obviously, we do have legal protection through the early part of 2025, but that's a high-margin product, as you know.

然後，阿米，就我們預期如何發展的毛利率而言，我們在準備好的評論中表示，我們確實預計我們的銷售成本佔收入的百分比將在剩下的時間裡繼續增加。 2023 年，這與我們今年看到的巨額合同製造收入密切相關。在沒有 2023 年之後的指導的情況下，我只能說，從趨勢角度來看，當你看看我們的一些更大的門票項目時，我們有反 CD20，它們利潤很高。它們有點持平甚至有所下降，這已經成為那裡的趨勢。你有 TECFIDERA，你在美國有仿製藥競爭。顯然，到 2025 年初我們確實有法律保護，但正如你所知，這是一種高利潤產品。

And so when you look at the growth trajectory of those products versus the contract manufacturing, and we will continue to be aggressive in pursuing contract manufacturing opportunities if we can utilize them to fill space that we otherwise wouldn't use. You would expect that we would continue to see some pressure on the gross margin percentage. That's something that we'll manage. We are seeing. We did have $34 million of idle capacity charges during the quarter. That is something that we hope will abate over time as LEQEMBI ramps up and we're able to fully utilize our facility in solid turns so that would be potentially an offset. But we don't see real material increases in our gross margin percentage, and that's something we're going to have to manage. And that's part of the reason why we put such a keen focus on our operating expenses and introduce such a meaningful cost reduction program.

因此，當你看看這些產品與合同製造的增長軌跡時，如果我們能夠利用它們來填補我們不會使用的空間，我們將繼續積極尋求合同製造機會。您可能會預計我們的毛利率將繼續面臨一些壓力。這是我們會處理的事情。我們正在看到。本季度我們確實有 3400 萬美元的閒置產能費用。我們希望隨著 LEQEMBI 的發展，這種情況會隨著時間的推移而減弱，並且我們能夠充分利用我們的設施，因此這可能是一種抵消。但我們的毛利率並沒有出現真正的實質性增長，這是我們必須應對的問題。這就是我們如此關注運營支出並推出如此有意義的成本削減計劃的部分原因。

We'll go next to Brian Skorney with Baird.

我們將和貝爾德一起去布萊恩·斯科尼旁邊。

Really just one, you guys had a role in developing both LEQEMBI and ADUHELM. And one of the things that seems to be jumping out as sort of the differential profile of these drugs in terms of ARIA rates. But seeing that those differences despite a very similar plaque removal. So I guess there's a lot of speculation and maybe remains a lot of uncertainty as to the underlying mechanism. But anything you can say in terms of sort of your thought process about how much of this may be sort of subspecies, target driven? How much of it may just be sort of a matter of [PK]? I mean, it seems like the comments on subcu indicates -- at least some of it may be Cmax-driven, but just how are you guys currently thinking about the mechanism underpinning ARIA?

實際上只有一個，你們在 LEQEMBI 和 ADUHELM 的開發中發揮了作用。其中一件事似乎是這些藥物在 ARIA 率方面的差異。但儘管去除的牙菌斑非常相似，但還是看到了這些差異。所以我想有很多猜測，而且對於潛在的機制可能仍然存在很多不確定性。但你能說一下你的思維過程嗎？其中有多少可能是亞種、目標驅動的？其中有多少可能只是[PK]的問題？我的意思是，似乎 subcu 上的評論表明——至少其中一些可能是 Cmax 驅動的，但你們目前如何考慮支撐 ARIA 的機制？

Yes. Thank you, Brian. So overall, I think we don't fully understand the mechanism of ARIA, but the data have been replicated for LEQEMBI in terms of a low incidence of ARIA, in the sense that when you compare it with some of the other anti-amyloid -- anti-beta amyloid antibodies, it is significantly lower and replicated twice.

是的。謝謝你，布萊恩。因此，總的來說，我認為我們並不完全了解 ARIA 的機制，但就 ARIA 的低發生率而言，LEQEMBI 的數據已得到重複，從某種意義上說，當您將其與其他一些抗澱粉樣蛋白進行比較時 - - 抗β澱粉樣蛋白抗體，其顯著降低並重複兩次。

So for example, in the Clarity AD study, we had an ARIA-E rate of about 12.6%, but with donanemab, we see an ARIA-E rate of 24%, a very similar sort of proportions with ARIA-H. So I think that it also depends on the population that has been recruited. And as Chris mentioned, these populations have been slightly different with MCI being -- and the early population because we really believe that patients need to be treated earlier. So that could be playing a role. But I think overall, it's very hard to assess exactly what may be driving the differential dates.

例如，在 Clarity AD 研究中，我們的 ARIA-E 率為約 12.6%，但對於 donanemab，我們看到 ARIA-E 率為 24%，與 ARIA-H 的比例非常相似。所以我認為這也取決於招募的人口。正如 Chris 提到的，這些人群與 MCI 以及早期人群略有不同，因為我們確實相信患者需要更早接受治療。所以這可能會發揮作用。但我認為總體而言，很難準確評估是什麼導致了差異日期。

What I think we can say is that the observation that the incidence is significantly different. And therefore, I believe that the benefit risk is also different. And that, I think, is what doctors should be looking at. Couple that with the efforts that we do have a very clear window of susceptibility with ARIA and LEQEMBI that we see, we know that it's really pretty much circumscribed to the first 6 months. There's no titration. So we see the rates that we do. And then it really (inaudible) and recurrence is very, very low. This helps us because we can help physicians really get on board, stay on the monitoring plan, and that is really the focus of Eisai with better understanding ARIA program.

我想我們可以說的是，觀察到的發生率是顯著不同的。因此，我認為收益風險也是不同的。我認為這才是醫生應該關注的。再加上我們所做的努力，我們看到 ARIA 和 LEQEMBI 具有非常清晰的易感性窗口，我們知道它實際上幾乎僅限於前 6 個月。沒有滴定。所以我們看到了我們所做的費率。然後它真的（聽不清）並且複發率非常非常低。這對我們很有幫助，因為我們可以幫助醫生真正參與進來，堅持監測計劃，這確實是衛材的重點，可以更好地了解 ARIA 計劃。

So I think overall, we have to look at the benefit risk. We've got the broad AD population that did not recruit via tau sub-stratification for LEQEMBI, and we have the results right up to tau PET because everybody, as you know, amyloid kind of progresses into the neurofibrillary tangles. And so it's really helpful to understand that there is a broad application with LEQEMBI and then there's a risk profile that's also in the broader population.

所以我認為總的來說，我們必須考慮利益風險。我們已經獲得了廣泛的 AD 人群，這些人群並未通過 tau 亞分層進行 LEQEMBI 招募，並且我們得到了 tau PET 的結果，因為如您所知，每個人的澱粉樣蛋白都會進展為神經原纖維纏結。因此，了解 LEQEMBI 的廣泛應用以及更廣泛人群中的風險狀況確實很有幫助。

I think with -- we do have a box warning, as you know, with the APOE4 patients who do have a higher rate of ARIA. And this, again, is really what we see across the different molecules.

我認為，如您所知，我們確實對 APOE4 患者的 ARIA 發生率較高進行了方框警告。這又是我們在不同分子中看到的真實情況。

One of the things, Priya, that was -- so (inaudible) and Priya over the weekend after this super interesting paper all that happened at AAIC and the differences. And the thing that struck me is just really how complex this is and how much there is to really analyze and understand. But one of the things that struck me was that there is a difference in safety not just in the broad population, but we see that in every subgroup, too.

其中一件事，Priya，就是——所以（聽不清）Priya 在這篇超級有趣的論文之後的周末在 AAIC 發生了所有事情以及差異。令我震驚的是，這確實是多麼複雜，需要真正分析和理解的東西有多少。但令我震驚的一件事是，安全性不僅存在於廣大人群中，而且在每個亞群體中也存在差異。

Yes. Every subgroup.

是的。每個子組。

I mean, if you're looking at the APOE group, heterozygous, homozygous is a difference. And if these drugs were similar, you wouldn't expect such a dramatic difference. I mean we're talking about -- in some subgroups, it can be as much as 3:1 ratio on the safety. And that's why I think we're going to spend an awful lot more time analyzing what's really going on here. And that's what I said at the outset. We're really just at the start of this. There's still so much we don't know, but this is going to generate an awful lot of research and we're going to start digging into this and understanding all of these different subtleties that are there.

我的意思是，如果你觀察 APOE 群體，雜合子和純合子是有區別的。如果這些藥物相似，你就不會想到會有如此巨大的差異。我的意思是，我們正在討論 - 在某些子組中，安全性比例可能高達 3:1。這就是為什麼我認為我們將花費更多時間來分析這裡到底發生了什麼。這就是我一開始所說的。我們真的才剛剛開始。我們還有很多不知道的事情，但這將產生大量的研究，我們將開始深入研究並理解其中存在的所有這些不同的微妙之處。

But I think these differences are going to be quite important. As Priya said, the jury is still out on that, but we have an awful lot of signs about what's really going on here. And that's why as a company, at Biogen, we don't see the launch of LEQEMBI as the end to our commitment to Alzheimer's. As Priya pointed out, we have other programs in Alzheimer's and we're going to be continuing to do research because it is really our ambition to be along with our partners at Eisai, the absolute leader in what we think is going to be an extremely significant market.

但我認為這些差異將非常重要。正如 Priya 所說，對此還沒有定論，但我們有很多跡象表明這裡到底發生了什麼。這就是為什麼作為百健（Biogen）公司，我們並不認為 LEQEMBI 的推出意味著我們對阿爾茨海默病的承諾的結束。正如 Priya 指出的那樣，我們在阿爾茨海默氏症方面還有其他項目，我們將繼續進行研究，因為我們的雄心是與衛材 (Eisai) 的合作夥伴合作，衛材 (Eisai) 是我們認為這將是一個極其重要的領域的絕對領導者。重要的市場。

Next question comes from Chris Schott with JPMorgan.

下一個問題來自摩根大通的克里斯·肖特。

I just wanted to -- I appreciate all the color on the call, but I just want to come back to the LEQEMBI and kind of the ramp from here. I know you've talked about this being kind of a gradual process. But based on the early feedback you've had from the market with the launch, I guess any incremental color of -- is this going faster or slower than you might have anticipated? And maybe just as part of that, what have been the biggest kind of positives or negatives on the rollout so far as you just try to kind of better assess? How to think about these next few quarters and years from here?

我只是想——我很欣賞通話中的所有色彩，但我只想回到 LEQEMBI，從這裡開始。我知道你說過這是一個漸進的過程。但根據您在發佈時從市場獲得的早期反饋，我猜想任何增量顏色 - 這會比您預期的更快還是更慢？也許只是其中的一部分，就您試圖更好地評估而言，推出過程中最大的積極或消極因素是什麼？如何思考接下來的幾個季度和幾年？

Well, as to what you anticipate it's kind of hard, as I say, this is only the second time in my career where I've actually seen a brand-new therapeutic area actually open up. And so when you think about Alzheimer's patients and visiting neurologists, beyond cognitive tests and as I say, perhaps prescribing the anti-cholinergic like donepezil hasn't really been much to do. And now we do have a treatment. And this is going to upend a lot of the processes within Neurology practices. It's extremely exciting. But really, the uptake is geared on how prepared are the sites. And this is variable around the country. You've had some sites. Obviously, they've been involved in clinical trials. Some of them have different patient populations and we see that some sites are quite advanced and are ready to go. Some sites have been more in a wait-and-see mode, but I think are all ramping up.

好吧，至於你的預期，這有點困難，正如我所說，這只是我職業生涯中第二次真正看到一個全新的治療領域真正開放。因此，當你想到阿爾茨海默病患者和拜訪神經科醫生時，除了認知測試之外，正如我所說，也許開多奈哌齊等抗膽鹼能藥物並沒有多大作用。現在我們確實有了治療方法。這將顛覆神經病學實踐中的許多流程。這非常令人興奮。但實際上，採用率取決於網站的準備程度。全國各地的情況各不相同。您已經有一些網站了。顯然，他們已經參與了臨床試驗。其中一些有不同的患者群體，我們看到一些站點非常先進並且已經準備就緒。一些網站一直處於觀望狀態，但我認為它們都在加速發展。

One of the things that we have been doing is -- is really trying to figure out where are the sites that are really ready and actually deploying our resources to those sites with -- then a secondary type of approach to sites that aren't quite ready and helping them. So it all depends on really how advanced the sites are, how ready they are that it's really going to define the uptake. And that's how we have to target our resources to that and really assess the site activation, if you like.

我們一直在做的事情之一是 - 真正試圖找出真正準備好的站點在哪裡，並實際將我們的資源部署到這些站點 - 然後對尚未完全準備好的站點採取第二種方法準備好並幫助他們。因此，這完全取決於網站的先進程度，以及它們是否準備好，從而真正定義吸收率。如果您願意的話，這就是我們必須將資源定位到此並真正評估站點激活的方式。

But so far, we're getting a lot of positive feedback. Physicians are getting a lot of inquiries from patients. I think they will have to figure out exactly what's the right patient for this, and that's where we have to do a lot of education. And we have these online programs and other programs to help educate physicians. There's a significant amount. I mean you just talk about -- what we've been talking about in terms of these protofibrils, about the different patient populations, all of those things are going to engage the whole Neurology community here. But so far, everything is -- as far as we're concerned, the launch is going to plan.

但到目前為止，我們收到了很多積極的反饋。醫生收到了大量患者的詢問。我認為他們必須弄清楚什麼才是最適合的患者，這就是我們必須進行大量教育的地方。我們有這些在線計劃和其他計劃來幫助教育醫生。數量很大。我的意思是你只是談論——我們一直在談論這些原纖維，關於不同的患者群體，所有這些事情都將吸引整個神經病學界的參與。但到目前為止，就我們而言，一切都在按計劃進行。

Our last question comes from Paul Matteis with Stifel.

我們的最後一個問題來自保羅·馬蒂斯和斯蒂菲爾。

I wanted to just briefly come back to Zuranolone. I've been really surprised by the lack of discussion on the call in the prepared remarks compared to prior calls. And can you just -- am I overly reading into this? I guess you're gearing up for potentially a new antidepressant approval. And Chris, at one point, you called this your most undervalued asset. So are you as bullish on this drug as you were before? And I guess if you didn't get the MDD approval, but that only got PPD. How would Biogen execute on that opportunity? Thank you.

我想簡單地回顧一下 Zuranolone。與之前的電話會議相比，準備好的講話中缺乏對這次電話會議的討論，這讓我感到非常驚訝。你能不能——我是不是過度解讀了這一點？我猜你正在為新的抗抑鬱藥物的批准做準備。克里斯，您曾一度將其稱為您最被低估的資產。那麼您還像以前一樣看好這種藥物嗎？我想如果你沒有獲得 MDD 批准，那麼只會獲得 PPD。百健（Biogen）將如何利用這個機會？謝謝。

Look, we're in late-stage review. So I think it's pretty normal that we don't want to disturb that process. And we obviously don't want to say anything that affects the FDA. I have to confess to a little bit of superstitiousness on my side. And I just -- I'd like to see the FDA decision, and then we'll be happy to talk lots about it. But the opportunity is huge out there, Paul.

看，我們正處於後期審查階段。所以我認為我們不想打擾這個過程是很正常的。我們顯然不想說任何影響 FDA 的事情。我不得不承認我有一點迷信。我只是 - 我希望看到 FDA 的決定，然後我們會很樂意談論它。但保羅，機會是巨大的。

Great. Thanks, Chris and thanks to everybody today for joining.

偉大的。謝謝克里斯，也感謝今天大家的加入。

This does conclude today's conference 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。