Biogen Inc (BIIB) 2022 Q3 法說會逐字稿

Good morning. My name is Jennifer, and I will be your conference operator today. At this time, I'd like to welcome everyone to the Biogen Third Quarter 2022 Earnings Call and Business Update. (Operator Instructions)

早上好。我叫詹妮弗，今天我將擔任你們的會議接線員。此時，我想歡迎大家參加 Biogen 2022 年第三季度收益電話會議和業務更新。 （操作員說明）

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

謝謝你。我現在想將會議轉交給投資者關係主管 Mike Hencke 先生。 Hencke 先生，您可以開始您的會議了。

Good morning, and welcome to Biogen's Third Quarter 2022 Earnings Call. Before we begin, I encourage everyone to go to the Investors section of biogen.com to find the earnings release and related financial tables, including our GAAP financial measures and the 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.

早上好，歡迎來到 Biogen 的 2022 年第三季度財報電話會議。在我們開始之前，我鼓勵大家去 biogen.com 的投資者部分找到收益發布和相關財務表格，包括我們今天將討論的 GAAP 財務指標和 GAAP 與非 GAAP 財務指標的調節。表 1 和表 2 提供了我們的 GAAP 財務數據，表 4 包括我們的 GAAP 與非 GAAP 財務結果的對賬。

We believe non-GAAP financial results better represent the ongoing economics of our business and reflect how we manage the business internally. We have also posted slides on our website that follow the discussions related to this call. I would like to point out that we will be making forward-looking statements, which are based on our current expectations and beliefs. 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.

我們相信，非 GAAP 財務業績更好地代表了我們業務的持續經濟狀況，並反映了我們如何在內部管理業務。我們還在我們的網站上發布了幻燈片，跟進與本次電話會議相關的討論。我想指出，我們將根據我們目前的預期和信念做出前瞻性陳述。這些陳述受某些風險和不確定因素的影響，我們的實際結果可能存在重大差異。我鼓勵您查閱我們在 SEC 文件中討論的風險因素以獲取更多詳細信息。

On today's call, I am joined by our Chief Executive Officer, Michel Vounatsos; Dr. Priya Singhal, Interim Head of Research and Development; and our CFO, Mike McDonnell. (Operator Instructions) I will now turn the call over to Michel.

在今天的電話會議上，我們的首席執行官米歇爾·沃納索斯 (Michel Vounatsos) 也加入了我的行列；研發臨時主管 Priya Singhal 博士；以及我們的首席財務官 Mike McDonnell。 （操作員說明）我現在將電話轉給米歇爾。

Good morning, everyone, and thank you for joining us. This is an exciting time for Biogen. In addition to key developments across our pipeline, which includes 12 programs in Phase III or filed, we continue to execute progress and we are pleased to be raising our full year financial guidance.

大家早上好，感謝您加入我們。這對百健（Biogen）來說是一個激動人心的時刻。除了我們整個管道的關鍵發展（包括 12 個處於 III 期或已備案的項目）之外，我們繼續取得進展，我們很高興提高我們的全年財務指導。

I would like to begin by reviewing the important advances we made this quarter and what we believe they mean for Biogen. Priya will then review our recent progress in R&D and Mike will discuss our third quarter performance. First, together with Eisai, we were excited to announce the positive results from CLARITY AD, the Phase III study of lecanemab in early Alzheimer's disease. For over 15 years, Biogen has been working relentlessly to bring forward new therapeutics in Alzheimer's disease, incorporating both new insights in disease biology and clinical trial design.

我想首先回顧一下我們本季度取得的重要進展以及我們認為它們對百健（Biogen）的意義。然後，Priya 將回顧我們最近的研發進展，Mike 將討論我們第三季度的業績。首先，我們很高興與衛材一起宣布 CLARITY AD 的積極結果，CLARITY AD 是 lecanemab 治療早期阿爾茨海默病的 III 期研究。 15 年來，百健（Biogen）一直堅持不懈地致力於開發阿爾茨海默病的新療法，將疾病生物學和臨床試驗設計方面的新見解結合起來。

And today, we celebrate the positive CLARITY AD readout as a significant achievement in the treatment of Alzheimer's disease. The results from Clarity AD illustrated several key aspects of lecanemab's clinical profile, which we believe could provide a meaningful benefit for patients. First, lecanemab administration showed a highly statistically significant reduction in clinical decline as early as 6 months, which expanded over the 18 months study period on an absolute basis, consistent with the disease-modifying effect.

今天，我們慶祝積極的 CLARITY AD 讀數作為阿爾茨海默病治療的重大成就。 Clarity AD 的結果說明了 lecanemab 臨床概況的幾個關鍵方面，我們認為這可以為患者帶來有意義的好處。首先，早在 6 個月時，lecanemab 給藥就顯示出具有高度統計學意義的臨床衰退減少，這在絕對基礎上在 18 個月的研究期間擴大，與疾病緩解作用一致。

Second, the study was positive on all key secondary endpoints. This includes measure of cognition as well as activities of daily living such as conducting personal finances, performing household tasks and independently traveling out of home. Third, the rate of ARIA within Clarity AD was within expectations. With an FDA decision on accelerated approval expected by January 6 of next year and Eisai's plan to file for traditional approval in the U.S., EU and Japan by the end of Q1 2023, lecanemab has the potential to be the first globally approved treatment to slow the progression of Alzheimer's disease.

其次，該研究在所有關鍵的次要終點上都是積極的。這包括認知測量以及日常生活活動，例如處理個人財務、執行家務和獨立出門旅行。第三，Clarity AD 中的 ARIA 率在預期之內。 FDA 預計將於明年 1 月 6 日做出加速批准的決定，衛材計劃在 2023 年第一季度末在美國、歐盟和日本申請傳統批准，lecanemab 有可能成為第一個全球批准的治療藥物，以減緩阿爾茨海默病的進展。

We look forward to working with Eisai as they continue to engage both regulators and CMS with a goal of ensuring that people with Alzheimer's disease have access to important new treatments. We believe that Clarity AD results underscore the progress we are making in the fight against Alzheimer's. But Biogen will not stop here. We plan to build upon our current learnings as we continue to advance a diversified pipeline of potential Alzheimer's treatment. This includes 2 clinical-stage assets targeting tau pathology, BIIB080, our Phase II-ready antisense oligonucleotide and BIIB113, a Phase I small molecule.

我們期待與衛材合作，因為衛材將繼續與監管機構和 CMS 合作，以確保阿爾茨海默病患者能夠獲得重要的新療法。我們相信 Clarity AD 的結果凸顯了我們在抗擊阿爾茨海默氏症方面取得的進展。但百健不會就此止步。我們計劃在我們目前的學習基礎上繼續推進潛在阿爾茨海默氏症治療的多元化管道。這包括 2 個針對 tau 病理學的臨床階段資產，BIIB080，我們的 II 期準備好的反義寡核苷酸和 BIIB113，一個 I 期小分子。

Beyond Alzheimer's Biogen has important opportunities in other therapeutic areas where the unmet medical need remains significant. This includes depression where, together with Sage, we are continuing to advance the regulatory filing for zuranolone in both major depressive disorders and postpartum depression. With a novel mechanism of action, efficacy observed as early as 3 days and a consistent safety and tolerability profile across 8 clinical studies, we believe that zuranolone, if approved, could be a meaningful new therapy for depression.

超越阿爾茨海默氏症 百健（Biogen）在其他未滿足醫療需求仍然很大的治療領域擁有重要機會。這包括抑鬱症，我們與 Sage 一起繼續推進 zuranolone 在重度抑鬱症和產後抑鬱症方面的監管備案。憑藉全新的作用機制、早在 3 天就觀察到療效以及在 8 項臨床研究中一致的安全性和耐受性，我們相信，如果獲得批准，祖蘭諾酮可能成為一種有意義的抑鬱症新療法。

Second, the FDA has accepted our filing for tofersen in SOD1-ALS under the accelerated approval pathway and granted priority review. While the study did not meet the primary endpoint at 6 months, longer follow-up has shown that patients who remain on tofersen experienced a slow rate of decline in key clinical measures, including lung functions, muscle strength and quality of life. We are truly encouraged by these results in such a debilitating and fatal disease and look forward to an FDA decision expected by April of next year.

其次，FDA 已經接受了我們在 SOD1-ALS 加速審批途徑下提交的 tofersen 申請，並授予優先審評。雖然該研究在 6 個月時未達到主要終點，但更長時間的隨訪表明，繼續使用 tofersen 的患者在關鍵臨床指標（包括肺功能、肌肉力量和生活質量）方面經歷了緩慢的下降。我們對這種使人衰弱和致命的疾病的這些結果感到由衷的鼓舞，並期待 FDA 預計在明年 4 月做出決定。

We believe this near-term opportunities, along with new launches of biosimilars, have the potential to drive renewed growth and position us to have 5 key franchises by 2025. Furthermore, we see the potential for additional growth drivers in the mid to late 2020s in areas such as Parkinson's disease, lupus and stroke, all with programs currently in Phase III. Overall, we believe that we are at an inflection point in CNS drug discovery and development. And these recent developments embody key advancements that are being made in neuroscience.

我們相信，這一近期機會以及新推出的生物仿製藥有可能推動新的增長，並使我們到 2025 年擁有 5 個主要特許經營權。此外，我們認為在 2020 年代中後期可能會出現額外的增長動力帕金森病、狼瘡和中風等領域，所有項目目前都處於 III 期。總的來說，我們認為我們正處於 CNS 藥物發現和開發的轉折點。這些最近的發展體現了神經科學正在取得的重大進展。

For years, Biogen has been expanding our expertise and capabilities in this area. And we believe that we are well positioned to remain a leader in neuroscience as we work to usher in the new next wave of CNS therapeutics while also advancing our portfolio in specialized immunology where we have 4 late-stage studies in lupus.

多年來，百健（Biogen）一直在擴展我們在這一領域的專業知識和能力。我們相信，我們有能力繼續保持神經科學領域的領導者地位，因為我們致力於引領下一波 CNS 療法，同時也推進我們在專業免疫學方面的產品組合，我們在狼瘡方面進行了 4 項後期研究。

I will now turn the call over to Priya for a more detailed update on our recent progress in R&D.

我現在將電話轉給 Priya，以更詳細地了解我們最近的研發進展。

Thank you, Michel, and good morning, everyone. As Michel mentioned, we had several exciting R&D achievements this past quarter that meaningfully advance the potential of our pipeline, which includes 30 programs, 12 of which are in Phase III or filed in order to deliver new impactful therapies for patients and drive renewed growth for the company.

謝謝你，米歇爾，大家早上好。正如 Michel 所提到的，我們在上個季度取得了幾項令人興奮的研發成就，這些成就顯著提升了我們管道的潛力，其中包括 30 個項目，其中 12 個處於 III 期或已備案，旨在為患者提供新的有影響力的療法並推動新的增長公司。

Starting with Alzheimer's disease. Together with Eisai, we were very excited to announce the positive results of the Clarity AD study, evaluating lecanemab in early Alzheimer's disease. The primary endpoint of the study was a change from baseline on CDR-Sum of Boxes, a well-established measure of cognition and function in Alzheimer's disease. The study met the primary endpoint and lecanemab reduced clinical decline on the CDR-Sum of Boxes compared with placebo at 18 months by 0.45, representing a treatment difference of 27%.

從阿爾茨海默病開始。我們很高興與衛材一起宣布 Clarity AD 研究的積極結果，該研究評估了 lecanemab 在早期阿爾茨海默病中的作用。該研究的主要終點是 CDR-Sum of Boxes 相對於基線的變化，這是阿爾茨海默氏病認知和功能的公認衡量標準。該研究達到了主要終點，與 18 個月時的安慰劑相比，lecanemab 使 CDR-Sum of Boxes 的臨床下降減少了 0.45，表示治療差異為 27%。

We also observed a highly statistically significant reduction in CDR-Sum of Boxes versus placebo as early as 6 months. We believe this demonstrates a rapid onset of efficacy and a significant change in CDR-Sum of Boxes versus placebo. Furthermore, the effect on CDR-Sum of Boxes expanded over the 18-month study period on an absolute basis, suggesting that lecanemab was exerting a disease-modifying effect.

早在 6 個月時，我們還觀察到與安慰劑相比，盒的 CDR 總和在統計學上具有高度顯著性降低。我們相信這證明了療效的快速起效以及 CDR-Sum of Boxes 與安慰劑相比的顯著變化。此外，在 18 個月的研究期間，對盒的 CDR 總和的影響在絕對基礎上擴大，表明 lecanemab 正在發揮疾病緩解作用。

The study also met all key secondary endpoints, reinforcing lecanemab's impact on cognition and function. This includes a statistically significant reduction in amyloid plaques in the brain as well as additional clinical assessments such as the ADCS-MCI-ADL, a caregiver-rated assessment of activities of daily living relative to placebo. We believe that these efficacy results, when combined with an observed overall incidence of ARIA of approximately 21%, highlights the potential for lecanemab to be a leading disease-modifying treatment for Alzheimer's disease.

該研究還滿足了所有關鍵的次要終點，加強了 lecanemab 對認知和功能的影響。這包括在統計學上顯著減少大腦中的澱粉樣蛋白斑塊以及其他臨床評估，例如 ADCS-MCI-ADL，這是一種護理人員評估的日常生活活動相對於安慰劑的評估。我們認為，這些療效結果與觀察到的 ARIA 總發生率約為 21% 相結合，突顯了 lecanemab 成為阿爾茨海默病領先疾病緩解療法的潛力。

Eisai will present the Clarity AD study results at CTAD in November and intends to publish the findings in a peer-reviewed medical journal. The lecanemab filing under the accelerated approval pathway is currently under review with a PDUFA date of January 6, 2023. The FDA has also agreed that the Clarity AD could serve as a confirmatory study to verify the clinical benefit of lecanemab. Accordingly, we expect Eisai will file for traditional approval of lecanemab in the U.S. as soon as possible, following a positive FDA decision on accelerated approval. This filing is expected by the end of Q1 2023, along with marketing authorization applications in the EU and Japan expected by the end of Q1 2023 as well.

衛材將於 11 月在 CTAD 上展示 Clarity AD 研究結果，並打算在同行評審的醫學期刊上發表研究結果。加速批准途徑下的 lecanemab 申請目前正在審查中，PDUFA 日期為 2023 年 1 月 6 日。FDA 還同意 Clarity AD 可以作為驗證性研究來驗證 lecanemab 的臨床益處。因此，我們預計衛材將在 FDA 做出加速批准的積極決定後，盡快在美國申請 lecanemab 的傳統批准。該申請預計在 2023 年第一季度末提交，歐盟和日本的上市許可申請也預計在 2023 年第一季度末提交。

Eisai has also been engaging with the Centers of Medicare and Medicaid Services as they work to maximize access for patients. Beyond these regulatory and access engagements, together with Eisai, we are also advancing a comprehensive development program for lecanemab, which includes, first, the ongoing AHEAD 3-45 preclinical study to evaluate lecanemab when administered earlier in disease, when amyloid pathology is present but before the onset of cognitive impairment.

衛材還一直與醫療保險和醫療補助服務中心合作，因為他們致力於最大限度地為患者提供服務。除了這些監管和准入方面的合作，我們還與衛材一起推進了 lecanemab 的綜合開發計劃，其中首先包括正在進行的 AHEAD 3-45 臨床前研究，以評估 lecanemab 在疾病早期給藥時的情況，當澱粉樣蛋白病理存在但在認知障礙發作之前。

Second, investigating a potential maintenance dosing regimen with the goal of reducing the lecanemab dosing frequency over time. And the development of a subcutaneous formulation of lecanemab. At AAIC earlier this year, Eisai presented bioavailability data from a Phase I study comparing IV versus subcutaneous dosing as well as modeling and simulation data illustrating that a fixed subcutaneous dose of 720 milligrams administered weekly may potentially result in comparable exposure and efficacy to the current IV formulation while potentially lowering the incidence of ARIA.

其次，研究潛在的維持給藥方案，目的是隨著時間的推移減少 lecanemab 的給藥頻率。並開發了 lecanemab 的皮下製劑。在今年早些時候的 AAIC 上，衛材展示了一項 I 期研究的生物利用度數據，該研究比較了靜脈給藥與皮下給藥以及建模和模擬數據，這些數據表明每週給予 720 毫克的固定皮下劑量可能會導致與目前靜脈給藥相當的暴露和療效配方同時可能降低 ARIA 的發生率。

With these results in hand, we are focused now on maintaining our leadership position in Alzheimer's disease over the long term. We have an industry-leading portfolio addressing both amyloid and tau pathologies, as well as a multi-target, multi-modality preclinical portfolio targeting a broad range of Alzheimer's disease biology.

有了這些結果，我們現在的重點是長期保持我們在阿爾茨海默病領域的領導地位。我們擁有行業領先的解決澱粉樣蛋白和 tau 病理學的產品組合，以及針對廣泛的阿爾茨海默病生物學的多目標、多模態臨床前產品組合。

Now I will turn to neuropsychiatry, where this quarter, Biogen and Sage presented new data that supports zuranolone's potential, if approved, as a novel treatment for both major depressive disorder and postpartum depression. This includes an updated analysis of the open-label ongoing longitudinal SHORELINE study in MDD, which showed that the medium time to onset first -- I'm sorry, the median time to first repeat treatment for patients who responded to the original 14-day treatment was 135 days for the 30-milligram cohort and 249 days for the 50-milligram cohort.

現在我將轉向神經精神病學，本季度，Biogen 和 Sage 提供了支持 zuranolone 潛力的新數據，如果獲得批准，作為一種治療重度抑鬱症和產後抑鬱症的新方法。這包括對 MDD 中正在進行的開放標籤縱向 SHORELINE 研究的更新分析，該研究表明首次發作的中等時間——對不起，對最初 14 天有反應的患者首次重複治療的中位時間30 毫克隊列的治療時間為 135 天，50 毫克隊列的治療時間為 249 天。

We believe these data further support zuranolone as a potential meaningful new treatment for people suffering from depression. And we are continuing to work with Sage to advance a single U.S. regulatory filing for zuranolone in MDD and PPD expected to be completed by the end of this year.

我們相信這些數據進一步支持扎蘭諾酮作為一種潛在的對抑鬱症患者有意義的新療法。我們將繼續與 Sage 合作，推進 MDD 和 PPD 中祖蘭諾酮的單一美國監管備案，預計將於今年年底完成。

Moving on to our neuromuscular portfolio. The New England Journal of Medicine recently published 12-month data from the Phase III VALOR study and its open-label extension evaluating tofersen in SOD1-ALS, a progressive and rare genetic form of ALS, which currently has no targeted therapy. The published data showed that patients who initiated tofersen in VALOR experienced slower rates of decline across critical measures of function, muscle strength and quality of life versus those who transitioned from placebo to tofersen at the start of the open label extension 6 months later.

繼續我們的神經肌肉組合。 《新英格蘭醫學雜誌》最近公佈了 III 期 VALOR 研究的 12 個月數據及其在 SOD1-ALS 中評估 tofersen 的開放標籤擴展，SOD1-ALS 是一種進行性和罕見的 ALS 遺傳形式，目前尚無靶向治療。已發表的數據顯示，與在 6 個月後開放標籤擴展開始時從安慰劑過渡到托弗森的患者相比，在 VALOR 中開始使用托弗森的患者在功能、肌肉力量和生活質量等關鍵指標上的下降速度較慢。

Furthermore, tofersen led to a robust and sustained reduction in neurofilament, a marker of neuronal injury and neurodegeneration. In July, the tofersen filing was accepted by the FDA under the accelerated approval pathway with priority review. Subsequently, we submitted responses to information request by the FDA, which the FDA considered a major amendment to the application that will require additional time for review. As a result, the review period has been extended by 3 months with an FDA decision now expected by April 25, 2023.

此外，tofersen 導致神經絲的強烈和持續減少，神經絲是神經元損傷和神經變性的標誌。 7 月，FDA 以優先審評的加速審批途徑受理了 tofersen 申請。隨後，我們提交了對 FDA 的信息請求的回复，FDA 認為這是對申請的重大修改，需要額外的時間進行審查。因此，審查期延長了 3 個月，現在預計 FDA 將於 2023 年 4 月 25 日做出決定。

In movement disorders, together with Denali, we initiated our second late-stage clinical trial for BIIB122, a small molecule LRRK2 inhibitor. The Phase III LIGHTHOUSE study will evaluate BIIB122 in individuals with a confirmed pathogenic LRRK2 mutation. Given that LRRK2 activity is believed to regulate lysosomal function and underlying biological pathway implicated in Parkinson's disease, we are also advancing the Phase IIb LUMA study in idiopathic Parkinson's disease, which we initiated earlier this year.

在運動障礙方面，我們與 Denali 一起啟動了 BIIB122（一種小分子 LRRK2 抑製劑）的第二次後期臨床試驗。 III 期 LIGHTHOUSE 研究將在確認致病性 LRRK2 突變的個體中評估 BIIB122。鑑於 LRRK2 活性被認為可以調節帕金森病相關的溶酶體功能和潛在生物學途徑，我們還在推進我們今年早些時候啟動的針對特發性帕金森病的 IIb 期 LUMA 研究。

Moving on to specialized immunology. We were excited to announce the initiation of the Phase II/III study of litifilimab or BIIB059 in cutaneous lupus erythematosus, or CLE. The prior Phase II LILAC study of litifilimab met the primary endpoints in both parts of the study, evaluating safety and efficacy in individuals with CLE and systemic lupus erythematosus or SLE. The detailed Phase II results were recently published as 2 separate manuscripts in the New England Journal of Medicine.

繼續學習專業免疫學。我們很高興地宣布啟動 litifilimab 或 BIIB059 治療皮膚紅斑狼瘡 (CLE) 的 II/III 期研究。 Litifilimab 之前的 II 期 LILAC 研究滿足了研究的兩個部分的主要終點，評估了 CLE 和系統性紅斑狼瘡或 SLE 患者的安全性和有效性。詳細的 II 期結果最近作為 2 篇獨立的手稿發表在《新英格蘭醫學雜誌》上。

The Phase II/III study in CLE builds upon our mid- to late-stage pipeline in specialized immunology, which also includes 3 Phase III studies in SLE, 2 for litifilimab and 1 for dapirolizumab pegol, which we are developing in collaboration with UCB.

CLE 的 II/III 期研究建立在我們在專業免疫學的中後期管道之上，其中還包括 3 項 SLE III 期研究，2 項 litifilimab 和 1 項 dapirolizumab pegol，我們正在與 UCB 合作開發。

Looking ahead, we also have a number of exciting opportunities on the horizon. This includes the potential to deliver new therapies in Alzheimer's, depression and SOD1-ALS, initiation of mid- to late-stage programs in Alzheimer's disease and stroke and a proof-of-concept study readout in broad ALS.

展望未來，我們還有許多激動人心的機會。這包括為阿爾茨海默氏症、抑鬱症和 SOD1-ALS 提供新療法的潛力，啟動阿爾茨海默氏症和中風的中後期項目以及廣泛的 ALS 概念驗證研究讀出。

In conclusion, we believe that our recent progress exemplifies important elements of our broader approach to R&D at Biogen. This includes a focus on genetically validated targets and biology, the use of novel biomarkers to better characterize disease biology and target engagement, as well as our ability to employ the right therapeutic modality for the specific disease area or target.

總之，我們認為我們最近的進展體現了我們在百健（Biogen）更廣泛的研發方法中的重要元素。這包括關注經過基因驗證的目標和生物學、使用新型生物標誌物更好地表徵疾病生物學和目標參與，以及我們為特定疾病領域或目標採用正確治療方式的能力。

Together, we believe these principles, combined with our ongoing prioritization effort, has the potential to increase the probability of success in disease areas with significant unmet need. I will now pass the call over to Mike.

我們相信，這些原則與我們正在進行的優先排序工作相結合，有可能增加在需求未得到滿足的疾病領域取得成功的可能性。我現在將電話轉給邁克。

Thank you, Priya, and good morning, everyone. I will provide some highlights of our financial performance for the third quarter and an update to our full year 2022 guidance. Please note that all financial comparisons are versus the third quarter of 2021.

謝謝你，Priya，大家早上好。我將提供我們第三季度財務業績的一些亮點，以及我們 2022 年全年指引的更新。請注意，所有財務比較均與 2021 年第三季度相比。

Total revenue for the third quarter was $2.5 billion, a decrease of 10% at actual currency and 8% at constant currency. Non-GAAP diluted EPS in the third quarter was $4.77, which was flat versus the third quarter of 2021. Total MS revenue, inclusive of OCREVUS royalties, was $1.6 billion, which was a decrease of 11% at actual currency and 9% at constant currency.

第三季度總收入為 25 億美元，按實際匯率計算下降 10%，按固定匯率計算下降 8%。第三季度非 GAAP 稀釋後每股收益為 4.77 美元，與 2021 年第三季度持平。MS 總收入（包括 OCREVUS 特許權使用費）為 16 億美元，按實際貨幣計算下降 11%，按固定匯率計算下降 9%貨幣。

Global TECFIDERA revenue of $339 million, decreased 32% at actual currency and 30% at constant currency. We saw continued erosion of TECFIDERA in the U.S. due to generics and an impact from generics outside of the U.S., primarily in Germany. We continue to see new generic launches in the EU. Earlier this month, the Advocate General of the European Court of Justice issued a nonbinding advisory opinion. We would expect TECFIDERA to have statutory market protection until at least February of 2024 if the court adopts the advisory opinion. There is no deadline for the court to issue its final decision, but we understand that approximately 3 to 5 months after issuance of the Advocate General's opinion is typical.

TECFIDERA 的全球收入為 3.39 億美元，按實際貨幣計算下降 32%，按固定匯率計算下降 30%。由於仿製藥以及美國以外（主要是德國）仿製藥的影響，我們看到 TECFIDERA 在美國的持續侵蝕。我們繼續在歐盟看到新的仿製藥上市。本月早些時候，歐洲法院總檢察長發表了一份不具約束力的諮詢意見。如果法院採納諮詢意見，我們預計 TECFIDERA 將至少在 2024 年 2 月之前獲得法定市場保護。法院發布最終決定沒有最後期限，但據我們了解，一般情況下，在總檢察長發表意見後大約 3 至 5 個月。

Separately, we are filing actions to enforce our recently granted European TECFIDERA dosing patent, which expires in 2028. We have been successful in obtaining preliminary injunctions in some countries and unsuccessful in others, including Germany and France. Until we either affirm TECFIDERA's entitlement to statutory market protection in the EU or successfully assert our patent, generics can continue to sell in the countries where we do not have preliminary injunctions in place.

另外，我們正在提起訴訟，以強制執行我們最近授予的歐洲 TECFIDERA 劑量專利，該專利將於 2028 年到期。我們已在一些國家成功獲得初步禁令，但在其他國家（包括德國和法國）卻未獲成功。在我們確認 TECFIDERA 在歐盟享有法定市場保護的權利或成功主張我們的專利之前，仿製藥可以繼續在我們沒有初步禁令的國家/地區銷售。

Global VUMERITY revenue of $138 million increased 14% at actual currency and 15% at constant currency. U.S. VUMERITY revenue increased 6% with higher volumes, partially offset by increased discounts and allowances. VUMERITY is being impacted by both payer pressure and a contraction of the oral segment of the market in the United States. We continue to work with our contract manufacturing supplier to address potential supply constraints for VUMERITY. We have identified the root cause, implemented manufacturing changes required to resolve the issue and are now working to secure necessary related regulatory approvals.

全球 VUMERITY 收入為 1.38 億美元，按實際貨幣計算增長 14%，按固定匯率計算增長 15%。美國 VUMERITY 收入增長 6%，銷量增加，部分被折扣和津貼增加所抵消。 VUMERITY 受到付款人壓力和美國口服市場收縮的影響。我們繼續與我們的合同製造供應商合作，以解決 VUMERITY 的潛在供應限制。我們已經確定了根本原因，實施了解決問題所需的製造變更，現在正在努力獲得必要的相關監管批准。

We do not anticipate a supply shortage in 2022 and are currently focused on rebuilding adequate inventory with the goal of assuring supply and reinitiating new country launches in 2023. Global TYSABRI revenue was $505 million, decreased 3% at actual currency and 1% at constant currency. U.S. TYSABRI revenue was negatively impacted by higher discounts and allowances and lower volume. Outside the U.S., we were pleased to see continued patient growth as well as good uptake of the subcutaneous formulation in the EU which has now been launched in over 25 markets with an average conversion rate of approximately 40%.

我們預計 2022 年不會出現供應短缺，目前正專注於重建充足的庫存，目標是確保供應並在 2023 年重新啟動新的國家/地區發布。全球 TYSABRI 收入為 5.05 億美元，按實際貨幣計算下降 3%，按固定匯率計算下降 1% .美國 TYSABRI 收入受到較高折扣和津貼以及較低銷量的負面影響。在美國以外，我們很高興看到患者持續增長以及皮下製劑在歐盟的良好吸收，該製劑現已在超過 25 個市場推出，平均轉化率約為 40%。

Although the composition of matter patents for TYSABRI have expired, we have other patents related to the making and using of TYSABRI, including those listed in our 10-K. We'll continue to enforce this IP, including filing suit against Sandoz in the United States. Global interferon revenue of $336 million, decreased 13% at actual currency and 12% at constant currency and was impacted by the continued shift from the injectable platforms to oral or high efficacy therapies.

雖然 TYSABRI 的物質組成專利已經過期，但我們還有其他與 TYSABRI 的製造和使用相關的專利，包括我們的 10-K 中列出的專利。我們將繼續執行此 IP，包括在美國對 Sandoz 提起訴訟。全球干擾素收入為 3.36 億美元，按實際貨幣計算下降 13%，按固定匯率計算下降 12%，並受到從注射平台向口服或高效療法的持續轉變的影響。

Moving to SMA. Global SPINRAZA revenue of $431 million, declined 3% at actual currency and increased 2% at constant currency. In the United States, SPINRAZA revenue was flat versus the prior year and we believe we may be seeing signs of stabilization in the U.S. Outside the U.S., excluding negative currency impacts, revenue increased due to volume growth in certain Asian markets as well as some positive pricing dynamics, partially offset by competition and the timing of shipments. Overall, we continue to believe that SPINRAZA has the potential to grow over time.

轉向 SMA。 SPINRAZA 的全球收入為 4.31 億美元，按實際貨幣計算下降 3%，按固定匯率計算增長 2%。在美國，SPINRAZA 的收入與上一年持平，我們認為我們可能會看到美國以外的穩定跡象，不包括負面的貨幣影響，由於某些亞洲市場的銷量增長以及一些積極的影響，收入增加定價動態，部分被競爭和發貨時間所抵消。總體而言，我們仍然相信 SPINRAZA 具有隨著時間的推移而增長的潛力。

Moving to our Biosimilars business. Revenue of $188 million, declined 7% at actual currency and 4% at constant currency. We saw an increase in sales volumes, which was offset by unfavorable pricing as well as negative currency impacts. We continue to expect a gradual launch of BYOOVIZ with more meaningful revenue contribution expected to begin in 2023.

轉向我們的生物仿製藥業務。收入為 1.88 億美元，按實際貨幣計算下降 7%，按固定匯率計算下降 4%。我們看到銷量有所增加，但被不利的定價和不利的貨幣影響所抵消。我們繼續預計 BYOOVIZ 將逐步推出，預計將於 2023 年開始貢獻更有意義的收入。

Total anti-CD20 revenue of $417 million was flat versus the prior year. Revenue from OCREVUS royalties increased 6%, which was offset by continued RITUXAN declines due to biosimilar competition.

抗 CD20 總收入為 4.17 億美元，與上年持平。來自 OCREVUS 特許權使用費的收入增長了 6%，這被 RITUXAN 因生物仿製藥競爭而持續下降所抵消。

Now moving on to expenses in the balance sheet. Third quarter non-GAAP cost of sales was $470 million, which includes $12 million of idle capacity charges. Going forward, we expect further pressure on gross margins due to shifts in product mix and potential idle capacity charges largely resulting from the suspension of drug product manufacturing for ADUHELM. Third quarter non-GAAP R&D expense was $549 million. This is compared to $702 million in the third quarter of 2021, which included approximately $165 million in upfront payments related to business development transactions as well as clinical trial closeout costs.

現在轉到資產負債表中的費用。第三季度非 GAAP 銷售成本為 4.7 億美元，其中包括 1200 萬美元的閒置產能費用。展望未來，我們預計，由於產品組合的變化和潛在的閒置產能費用，毛利率將面臨進一步壓力，這主要是由於 ADUHELM 的藥品生產暫停造成的。第三季度非 GAAP 研發費用為 5.49 億美元。相比之下，2021 年第三季度為 7.02 億美元，其中包括約 1.65 億美元的與業務開發交易相關的預付款以及臨床試驗收尾成本。

Non-GAAP SG&A was $562 million. This is compared to $651 million in the third quarter of 2021. The decrease in SG&A expense was driven primarily by cost savings initiatives. Third quarter collaboration profit sharing was a net expense of $45 million, primarily driven by our collaboration with Samsung Bioepis. Non-GAAP other expense was $55 million, primarily driven by interest expense.

非 GAAP SG&A 為 5.62 億美元。相比之下，2021 年第三季度為 6.51 億美元。SG&A 費用的減少主要是由成本節約舉措推動的。第三季度合作利潤分享是 4500 萬美元的淨支出，這主要是由於我們與 Samsung Bioepis 的合作。非 GAAP 其他費用為 5500 萬美元，主要由利息費用驅動。

In the third quarter, we generated $661 million in cash flow from operations. Capital expenditures were $59 million and free cash flow was $602 million. We repurchased 1.2 million shares of the company's common stock during the quarter for $250 million at an average price of $214 per share. We ended the quarter with $5.8 billion in cash and marketable securities, $6.3 billion in debt and approximately $500 million in net debt.

第三季度，我們產生了 6.61 億美元的運營現金流。資本支出為 5900 萬美元，自由現金流為 6.02 億美元。我們在本季度以 2.5 億美元的價格以每股 214 美元的平均價格回購了 120 萬股公司普通股。本季度結束時，我們擁有 58 億美元的現金和有價證券、63 億美元的債務和大約 5 億美元的淨債務。

Of note, in the third quarter, we received net proceeds of $583 million from the sale of one of our buildings in Cambridge as part of our office footprint optimization initiative. Additionally, in October, we paid $900 million plus fees and expenses to resolve the previously disclosed qui tam litigation. As a reminder, we expect to receive an additional $1.25 billion over the next 1.5 years from the sale of our equity stake in Samsung Bioepis, including approximately $813 million due in April of next year.

值得注意的是，在第三季度，作為我們辦公室佔地面積優化計劃的一部分，我們通過出售劍橋的一棟建築獲得了 5.83 億美元的淨收益。此外，在 10 月，我們支付了 9 億美元以及費用和開支來解決之前披露的 qui tam 訴訟。提醒一下，我們預計在未來 1.5 年內通過出售我們在 Samsung Bioepis 的股權獲得額外的 12.5 億美元，其中包括將於明年 4 月到期的約 8.13 億美元。

Overall, we remain in a very strong financial position with significant cash and financial capacity, including a $1 billion undrawn revolving credit facility to invest in growing the business over the long term. Before I turn to our updated guidance, let me say a few words about lecanemab. We are excited to be collaborating with Eisai on this important opportunity under a global 50-50 profit sharing agreement.

總體而言，我們的財務狀況仍然非常強勁，擁有大量現金和財務能力，包括 10 億美元的未提取循環信貸額度，用於投資於長期發展業務。在我轉向我們更新的指南之前，讓我先談談 lecanemab。我們很高興能根據一項全球 50-50 的利潤分享協議，在這個重要機會上與衛材合作。

As a reminder, Biogen has the right to co-commercialize and co-promote lecanemab with Eisai, who has final decision-making authority. After approval, our share of profits or losses will be booked as a component of other revenue. The lecanemab component of other revenue may be negative in the initial quarters of the launch. Please see Slide 26 in our earnings presentation for other accounting considerations.

提醒一下，百健（Biogen）有權與擁有最終決策權的衛材（Eisai）共同商業化和共同推廣lecanemab。經批准後，我們的利潤或虧損份額將作為其他收入的一部分入賬。在發布的最初幾個季度，其他收入的 lecanemab 部分可能為負數。請參閱我們的收益演示文稿中的幻燈片 26，了解其他會計考慮因素。

Let me now discuss our updated full year 2022 guidance. We are increasing our full year revenue guidance from our previous range of $9.9 billion to $10.1 billion to a new range of $10 billion to $10.15 billion and increasing our full year non-GAAP diluted EPS guidance from our previous range of $15.25 to $16.75 to a new range of $16.50 to $17.15. This guidance increase is primarily a result of better-than-expected top line performance and continued cost management.

現在讓我討論一下我們更新的 2022 年全年指南。我們將全年收入指引從之前的 99 億美元至 101 億美元增加到 100 億美元至 101.5 億美元的新範圍，並將我們的全年非 GAAP 稀釋後每股收益指引從之前的 15.25 美元至 16.75 美元增加到新的範圍範圍為 16.50 美元至 17.15 美元。這一指導增長主要是由於頂線業績好於預期和持續的成本管理。

Our guidance ranges for non-GAAP R&D expense, non-GAAP SG&A expense and our non-GAAP tax rate are all unchanged from prior guidance. As a reminder, we typically see a seasonally higher SG&A spend in the fourth quarter. This guidance assumes that foreign exchange rates as of September 30 will remain in effect for the remainder of the year, net of hedging activities. This financial guidance also assumes continued declines in RITUXAN revenue due to biosimilar competition, as well as continued erosion of TECFIDERA revenue due to generic entry. Please see our press release for other important guidance assumptions.

我們對非 GAAP 研發費用、非 GAAP SG&A 費用和我們的非 GAAP 稅率的指導範圍均與之前的指導一致。提醒一下，我們通常會在第四季度看到季節性較高的 SG&A 支出。本指引假設截至 9 月 30 日的外匯匯率將在今年剩餘時間保持有效，扣除對沖活動。該財務指南還假設由於生物仿製藥競爭導致 RITUXAN 收入持續下降，以及由於仿製藥進入而導致 TECFIDERA 收入持續下降。請參閱我們的新聞稿了解其他重要的指導假設。

In summary, we continue to execute well across our core business and are pleased to be raising our financial guidance for the year. We are excited about the recent lecanemab readout and believe our diversified pipeline across neuroscience, specialized immunology and biosimilars has the potential to return Biogen to growth over time as we continue to build a multifranchise portfolio.

總而言之，我們的核心業務繼續表現良好，並很高興提高今年的財務指引。我們對最近的 lecanemab 讀數感到興奮，並相信我們在神經科學、專業免疫學和生物仿製藥方面的多元化管道有可能隨著我們繼續建立多特許經營組合而使 Biogen 隨著時間的推移恢復增長。

As always, we remain focused on creating long-term value for our shareholders. And with that, we will now open the call for questions.

一如既往，我們仍然專注於為股東創造長期價值。有了這個，我們現在將開始提問。

(Operator Instructions) Your first question comes from the line of Umer Raffat with Evercore.

（操作員說明）您的第一個問題來自 Evercore 的 Umer Rafat 系列。

I had a question on the status of your relationship with Eisai. There's a lot of investor questions on it. And I was just really curious if you could speak to sort of the status of the relationship, if you expect Eisai to allow you to co-commercialize and that there's not been any sort of contractual disputes or anything like that?

我有一個關於您與衛材的關係狀況的問題。有很多投資者的問題。我真的很好奇你是否可以談談這種關係的狀態，你是否希望衛材允許你們共同商業化並且沒有任何合同糾紛或類似的事情？

Thanks for the question, Umer. I can tell you that the relationship is very solid since many years. I have the opportunity to meet and to align with our -- my counterpart on a very regular basis. And I will do that once more in the coming days. The team are working together very closely. The co-commercialization, co-marketing is being discussed while we speak and is not yet determined. And -- but overall, the relationship is sound and solid. Mike, do you want to add something?

謝謝你的問題，烏默。我可以告訴你，多年來，這種關係非常牢固。我有機會定期與我們的對手會面並保持一致。在接下來的幾天裡，我會再做一次。團隊緊密合作。我們正在討論共同商業化、共同營銷，但尚未確定。而且——但總的來說，這種關係是健全和穩固的。邁克，你想補充點什麼嗎？

No, I think that covers it. I would say that as we work together on the commercialization strategy, obviously Eisai has final decision-making rights, but it is a 50-50 profit share. And together, we're excited for the upcoming CTAD presentation, where more detailed study results will be shared.

不，我認為這涵蓋了它。我想說的是，在我們共同製定商業化戰略時，顯然衛材擁有最終決定權，但它是 50-50 的利潤分成。我們一起為即將到來的 CTAD 演示感到興奮，屆時將分享更詳細的研究結果。

We'll go to our next question from Brian Abrahams with RBC Capital Markets.

我們將與 RBC Capital Markets 的 Brian Abrahams 一起回答下一個問題。

Congrats on the quarter and on the lecanemab data. I'm curious how you envision reimbursement access for lecanemab with an accelerated versus a full approval? And I guess I'm wondering, based on you and your partner's ongoing CMS discussions, what your latest views are on whether top line results from Clarity AD would satisfy CMS' high-level evidence requirements to support NCD reconsideration in the case of an accelerated approval.

祝賀本季度和 lecanemab 數據。我很好奇您如何設想通過加速批准和完全批准獲得 lecanemab 的報銷途徑？我想我想知道，根據你和你的合作夥伴正在進行的 CMS 討論，你的最新觀點是關於 Clarity AD 的頂級結果是否會滿足 CMS 的高水平證據要求，以在加速的情況下支持 NCD 重新考慮贊同。

Thanks for this important question. I think it all depends to the strength of the evidence. We are very pleased with the top line results on the primary and secondaries. We are all looking forward for CTAD and for a coming publication in order to assess the level of evidence that will be considered by CMS and that will imply the path forward. Priya?

感謝您提出這個重要問題。我認為這完全取決於證據的強度。我們對小學和中學的頂級成績感到非常滿意。我們都期待著 CTAD 和即將出版的出版物，以評估 CMS 將考慮的證據水平，這將暗示前進的道路。普里亞？

Thank you, Michel. That's exactly right. And I'll just add that there is a -- there are a couple of scenarios that are outlined in the NCD. So for the accelerated approval scenario, it's essentially coverage only in the situation of a randomized controlled trial, which is essentially noncoverage. But for traditional approval, there is a range of options, I think, that the NCD indicates, which is that it could be covered in a CMS-approved prospective comparative study, including registries.

謝謝你，米歇爾。這是完全正確的。我只想補充一點——NCD 中概述了幾個場景。因此，對於加速批准方案，它基本上只是在隨機對照試驗的情況下才覆蓋，這基本上是非覆蓋。但是對於傳統的批准，我認為有一系列的選擇，NCD 表明，這可以包括在 CMS 批准的前瞻性比較研究中，包括註冊。

The strength and rigor of that kind of study will depend on the strength and rigor of the randomized controlled trial that affords the final traditional approval. So in that sense, we feel very confident about the strength of evidence. As you know, we met the primary endpoint with a treatment difference of 0.45, which translated to 27% versus placebo with lecanemab. And also all secondary endpoints were met in a highly statistical significant manner. And in addition, I would add that we had about 25% of an underrepresented population.

此類研究的強度和嚴謹性將取決於提供最終傳統批准的隨機對照試驗的強度和嚴謹性。因此，從這個意義上說，我們對證據的強度非常有信心。如您所知，我們達到了主要終點，治療差異為 0.45，與 lecanemab 安慰劑相比為 27%。並且所有次要終點都以高度統計顯著的方式得到滿足。此外，我要補充一點，我們有大約 25% 的未被充分代表的人口。

So we believe that it's very well designed and the results are very encouraging. The rest will remain to be seen, and Eisai is already engaging with CMS to discuss this. You specifically asked about reconsideration, so I'll just add a note there, that in the final scenario that NCD -- the final NCD did put out was that CMS would act with urgency and potentially a reconsideration could be considered. That could take 9 to 12 months from a historic precedent perspective. But I think in this sense, they have said that they would act with urgency. And that would be a full coverage without the need for prospective comparative studies. So I think we need to wait for the CTAD data and continue the engagement.

所以我們相信它的設計非常好，結果非常令人鼓舞。其餘的還有待觀察，衛材已經在與 CMS 進行討論。你特別詢問了關於重新考慮的問題，所以我只是在那裡添加一個註釋，在 NCD 的最終場景中 - 最終的 NCD 確實提出了 CMS 將採取緊急行動，並且可能會考慮重新考慮。從歷史先例的角度來看，這可能需要 9 到 12 個月。但我認為，從這個意義上說，他們已經表示會緊急行動。這將是一個全面的覆蓋範圍，不需要進行前瞻性比較研究。所以我認為我們需要等待 CTAD 數據並繼續參與。

Your next question comes from the line of Salveen Richter with Goldman Sachs.

你的下一個問題來自高盛的 Salveen Richter。

On the back of the lecanemab data, can you just walk us through how you're thinking about business development and portfolio prioritization?

在 lecanemab 數據的背後，你能告訴我們你是如何考慮業務發展和投資組合優先級的嗎？

I can tell you that we do remain very active on BDs -- in evaluating BD. Obviously, the portfolio is strong. And as we said during the prepared remarks, we have 12 Phase IIIs of filed products and we are getting prepared for AD, ALS, MDD and PPD. So we are all very busy. Nevertheless, BD is on the table because the portfolio can always be improved. And we are evaluating every week prospects and we are making progress. We've made more than 30 deals in the past few years, but we continue to be very active. Priya and Mike?

我可以告訴你，我們在 BD 方面仍然非常活躍——在評估 BD 方面。顯然，投資組合很強大。正如我們在準備好的評論中所說，我們有 12 個 III 期產品，我們正在為 AD 、 ALS 、 MDD 和 PPD 做好準備。所以我們都很忙。儘管如此，BD 還是擺在桌面上，因為產品組合總是可以改進的。我們每週都在評估前景，我們正在取得進展。在過去的幾年裡，我們已經完成了 30 多筆交易，但我們仍然非常活躍。普里亞和邁克？

So I think that's a great question. And just stepping back, as Michel mentioned during the remarks, we see ourselves as leaders in the Alzheimer's space. We believe that we've done a lot of evaluation of the scientific hypotheses, the biology. And we have set up our portfolio to be able to address both what in terms of the biology and also the when. So I think in terms of the biology, we've now had success with lecanemab. Previously, we've seen the results also with aducanumab and that's the Abeta hypothesis.

所以我認為這是一個很好的問題。正如米歇爾在講話中提到的那樣，退一步說，我們將自己視為阿爾茨海默氏症領域的領導者。我們相信我們已經對科學假設、生物學進行了大量評估。我們已經建立了我們的投資組合，以便能夠解決生物學方面的問題以及何時。所以我認為就生物學而言，我們現在已經在 lecanemab 上取得了成功。以前，我們也看到了 aducanumab 的結果，這就是 Abeta 假說。

In addition, we had our own study with a monoclonal antibody against tau, which did not work. So we did test that hypothesis with the extracellular tau and now we are positioned to initiate our Phase II with BIIB080, which is an antisense oligonucleotide that will address all post-translational forms of tau. So we believe that (inaudible) we believe we have a leading antisense oligonucleotide. Also, we have BIIB113 in Phase I, which addresses tau aggregation and addresses an enzymatic inhibition of tau aggregation.

此外，我們自己進行了針對 tau 的單克隆抗體的研究，但沒有奏效。所以我們確實用細胞外 tau 檢驗了這個假設，現在我們準備好用 BIIB080 啟動我們的第二階段，這是一種反義寡核苷酸，將解決 tau 的所有翻譯後形式。所以我們相信（聽不清）我們相信我們有領先的反義寡核苷酸。此外，我們在第一階段有 BIIB113，它解決了 tau 聚集並解決了對 tau 聚集的酶促抑制。

So we are really trying to tackle this from all the -- from the amyloid and the tau pathology basis. Behind that, in the preclinical space, we have also several other biologies that we are looking at very carefully in terms of targets and also modalities. So I think we have a very comprehensive approach. And with regards to when, I'm very pleased that we have lecanemab already being tested in preclinical Alzheimer's disease. So that's a study that's already ongoing, which will address what happens when you intervene with an anti-amyloid therapy, prior -- when you do have the amyloid aggregation but you don't have symptoms.

所以我們真的在努力從所有方面解決這個問題——從澱粉樣蛋白和 tau 病理學基礎。在這背後，在臨床前領域，我們還有其他幾種生物學，我們正在非常仔細地研究它們的目標和模式。所以我認為我們有一個非常全面的方法。關於何時，我很高興我們已經在臨床前阿爾茨海默病中對 lecanemab 進行了測試。所以這是一項已經在進行的研究，它將解決當你之前進行抗澱粉樣蛋白治療時會發生什麼——當你確實有澱粉樣蛋白聚集但你沒有症狀時。

So I think it's a very comprehensive approach. We are not going to stop here. We continue to look at very attractive targets. And I think BD and internal development will continue to be important. And finally, with lecanemab, we are testing 2 very important aspects in our development plan. Eisai is obviously the lead on this. In the Phase II open-label extension, we're looking at maintenance dosing. So what's the right frequency to continue to preserve the clinical decline progression stop.

所以我認為這是一個非常全面的方法。我們不會就此止步。我們繼續關注非常有吸引力的目標。而且我認為 BD 和內部開發將繼續很重要。最後，通過 lecanemab，我們正在測試我們開發計劃中的兩個非常重要的方面。衛材顯然是這方面的領頭羊。在 II 期開放標籤擴展中，我們正在研究維持劑量。那麼繼續保持臨床下降進展停止的正確頻率是多少。

And we are looking at subcutaneous development in the Phase III open-label extension. So I think overall, it's very, very comprehensive. And I think this will be a space that we will continue to invest to win. Thank you.

我們正在研究 III 期開放標籤擴展中的皮下開發。所以我認為總體而言，它非常非常全面。我認為這將是一個我們將繼續投資以贏得的空間。謝謝你。

Mike, do you want to add anything to BD?

Mike，你想給 BD 添加什麼嗎？

No, the only thing I would just quickly add is that -- I think you covered it, but I would just quickly add. You did not see BD activity during the quarter in the way of new collaborations or M&A, you should not read anything into that. We continue to have a very robust pipeline and we continue to look at a variety of deals. It does tend to be lumpy and you should fully expect that there will be more transactions in the future.

不，我要快速補充的唯一一件事是——我想你已經涵蓋了它，但我會快速補充。您在本季度沒有以新的合作或併購方式看到 BD 活動，您不應該對此進行任何解讀。我們繼續擁有非常強大的渠道，我們繼續關注各種交易。它確實往往是塊狀的，你應該充分期待未來會有更多的交易。

So as Priya said very eloquently, neurodegeneration takes more prominence in our productization process. And we are in a position to lead in AD and we are looking at actively at all the targets and assets we could acquire, but also beyond.

因此，正如 Priya 非常雄辯地說的那樣，神經變性在我們的產品化過程中更為突出。我們有能力在 AD 領域處於領先地位，我們正在積極尋找我們可以獲得的所有目標和資產，但也有可能超越。

We'll take your next question from Tim Anderson with Wolfe Research.

我們將從 Wolfe Research 的蒂姆安德森那裡回答你的下一個問題。

I have a question actually on ADUHELM. And it kind of relates to your earlier comments about your role with lecanemab still being under contemplation. I think a lot of folks are under the impression you've all but washed your hands and aren't really doing anything with ADUHELM. But from what I hear, that may not be the case. You're still pursuing a subcu version of the product. It sounds like you still may be trying to figure out a path forward to get CMS reimbursement for APOE4 carriers. And I'm wondering if that is true and if that could be a source of tension with Eisai? It's just not intuitive to me why you wouldn't be all-in on lecanemab instead and why you still may be active with ADUHELM.

我實際上有一個關於 ADUHELM 的問題。這與您之前關於您在 lecanemab 中的角色的評論有關，仍在考慮中。我認為很多人的印像是，您幾乎只洗手，並沒有真正使用 ADUHELM 做任何事情。但據我所知，情況可能並非如此。您仍在追求該產品的 subcu 版本。聽起來您可能仍在努力尋找獲得 APOE4 運營商 CMS 報銷的途徑。我想知道這是否屬實，這是否會導致與衛材的緊張關係？對我來說，為什麼你不會全押在 lecanemab 上，以及為什麼你仍然可能活躍於 ADUHELM，這對我來說並不直觀。

So we'll be all in on (inaudible), together with the great partners that we have, and we will do everything we can to secure access of the product to the patients after regulatory process. Nevertheless, the Clarity AD reinforces the finding that removing aggregated form of Abeta in the brain can be associated with the slowing down of the cognitive decline. And this is very important and this is what we have shown with ADU. And we have patients currently being dosed on the EMBARK study. And Priya will say more that.

因此，我們將全力以赴（聽不清），與我們擁有的優秀合作夥伴一起，我們將盡一切努力確保在監管程序後將產品提供給患者。然而，Clarity AD 強化了這樣一個發現，即去除大腦中聚集形式的 Abeta 可能與減緩認知衰退有關。這非常重要，這就是我們用 ADU 展示的內容。我們目前有患者正在接受 EMBARK 研究的給藥。 Priya 會說更多。

Yes. I'll actually -- I don't have a lot to add. What I'll say is that we are continuing to look at aducanumab, and we haven't made any decisions. For now, we believe that EMBARK data set is going to be very valuable to the scientific community. These are patients who have been on aducanumab and an anti-amyloid therapy for many years. In addition, we have a post-marketing requirement given that aducanumab was the first product to get accelerated approval and this is called the ENVISION study. So for now, both ENVISION and EMBARK continue.

是的。實際上，我沒有太多要補充的。我要說的是，我們正在繼續研究 aducanumab，我們還沒有做出任何決定。目前，我們相信 EMBARK 數據集將對科學界非常有價值。這些患者多年來一直接受 aducanumab 和抗澱粉樣蛋白治療。此外，我們有一個上市後要求，因為 aducanumab 是第一個獲得加速批准的產品，這被稱為 ENVISION 研究。所以現在，ENVISION 和 EMBARK 都在繼續。

Your next question comes from Chris Raymond with Piper Sandler.

你的下一個問題來自 Chris Raymond 和 Piper Sandler。

Just maybe a related question to the last one. So with your commercial infrastructure for ADUHELM largely sort of wound down here, how should we think about the ramp maybe in spend on lecanemab infrastructure, come January? And maybe talk about the lessons learned from ADUHELM and walk us through how you'll resource this launch here as you move from a potential accelerated approval to full approval?

也許只是與最後一個相關的問題。因此，隨著您的 ADUHELM 商業基礎設施在很大程度上在這裡逐漸減少，我們應該如何考慮 1 月份在 lecanemab 基礎設施上的支出增加？也許談談從 ADUHELM 中吸取的教訓，並向我們介紹當您從潛在的加速批准轉變為完全批准時，您將如何為此次發布提供資源？

Thanks for the question. I will start and Mike will add on. It was not reasonable based on the timeline and the gap between the ADU NCD decision and the lecanemab readout and then regulatory process to keep a large force on board. This will not have been reasonable. So we had no choice than to take the actions that we took. Now there is a new page. And together with the partners, we are assessing, considering the benefits -- the strength, the relative strength of each company, in each continent since we intend to file for full approval at the same time approximately in the U.S., in Europe and Japan, should we have the accelerated approval early in the year. We are planning the investment but we are not yet completely there. So we'll do that in a very paced and controlled manner and we'll take it from here. Mike?

謝謝你的問題。我會開始，邁克會補充。根據時間安排和 ADU NCD 決定與 lecanemab 讀數之間的差距，以及隨後的監管程序，保持大量人員參與是不合理的。這是不合理的。所以我們別無選擇，只能採取我們採取的行動。現在有一個新頁面。與合作夥伴一起，我們正在評估並考慮收益——實力，每個公司在每個大陸的相對實力，因為我們打算大約同時在美國、歐洲和日本申請全面批准，我們是否應該在今年年初獲得加速批准。我們正在計劃投資，但我們還沒有完全到位。因此，我們將以一種非常有節奏和可控的方式來做到這一點，我們將從這裡開始。麥克風？

Yes. I would just add to that, that as we continue discussions with Eisai on the commercialization strategy, it's a 50-50 profit share. They have the final decision rights, as we've said. There are learnings from the ADUHELM situation that obviously we all share openly. And I would say that I do feel very highly confident that we will -- you'll see a commercial ramp in spend that will have much better proximity to revenue than you saw on ADUHELM and obviously, there were a number of things on ADUHELM that didn't go in the direction that we had anticipated.

是的。我只想補充一點，隨著我們繼續與衛材就商業化戰略進行討論，這是 50-50 的利潤分成。正如我們所說，他們擁有最終決定權。顯然我們都公開分享了從 ADUHELM 情況中學到的東西。我要說的是，我確實非常有信心我們會做到——你會看到商業支出的增長，這將比你在 ADUHELM 上看到的更接近收入，而且顯然，ADUHELM 上有很多東西並沒有朝著我們預期的方向發展。

But I do feel confident that we'll be able to gauge it in a way that -- and Eisai will be able to gauge it in a way that the ramp in spend will have better proximity to revenue than what you saw on ADUHELM.

但我確實有信心，我們將能夠以一種方式來衡量它——衛材將能夠以一種方式來衡量它，即支出的增加將比你在 ADUHELM 上看到的更接近收入。

And I will say -- and if I may, I will say that we have a new process ahead of us. What we thought couple of years ago is that an accelerated will mean product launch and this was not the case. So here now, we have a new process that was outlined and then we'll be very much controlled in the way we spend the company's resource to scale up.

我會說——如果可以的話，我會說我們前面有一個新流程。幾年前我們的想法是，加速將意味著產品發布，但事實並非如此。所以現在在這裡，我們有一個概述的新流程，然後我們將在很大程度上控制我們花費公司資源以擴大規模的方式。

Your next question comes from Matthew Harrison with Morgan Stanley.

你的下一個問題來自摩根士丹利的馬修哈里森。

Great. I wanted to address another question that I think we get a lot from investors, which is about the potential for certain subgroups or populations to outperform and drive a significant part of the lecanemab top line results. So can you just maybe confirm, if that was the case, if for example a certain subgroup was a major driver of the response that you would have called that out in the top line? Or how should we think about that going into CTAD?

偉大的。我想解決另一個問題，我認為我們從投資者那裡得到了很多，這是關於某些子群體或人群表現優於並推動 lecanemab 頂線結果的重要部分的潛力。那麼，您是否可以確認，如果是這樣，例如，如果某個子組是響應的主要驅動力，那麼您會在第一行提到它嗎？或者我們應該如何考慮進入 CTAD？

I can take that question. Thanks for the question, Matthew. So overall, I'll just say that the Clarity AD met its primary endpoint, which was CDR-Sum of Boxes and this was with a p-value of 0.00005. So it was very, very highly significant. And this was a large trial. So it was about 1,800 participants with -- including the underrepresented population. And it met all its secondary endpoints, which were independent domains of cognition and function.

我可以接受這個問題。謝謝你的問題，馬修。所以總的來說，我只想說 Clarity AD 達到了它的主要終點，即 CDR-Boxes 總和，它的 p 值為 0.00005。所以這非常非常重要。這是一個很大的考驗。因此，大約有 1,800 名參與者——包括代表性不足的人群。它滿足了所有次要終點，即獨立的認知和功能領域。

So overall, we feel that the results are very, very positive and that they're very encouraging. Now details of subgroup analyses have not been shared by Eisai, and I think we need to wait for the CTAD to see more details about both the primary and the secondary endpoints. But at this point, I would say that overall, we believe that we just have to wait and we feel very encouraged by what we've seen on the top line. I won't be able to comment on exactly what you may or may not see. I think we have to wait for CTAD for that.

總的來說，我們認為結果非常非常積極，非常令人鼓舞。現在衛材還沒有分享亞組分析的細節，我認為我們需要等待 CTAD 看到更多關於主要和次要終點的細節。但在這一點上，我要說的是，總的來說，我們相信我們只需要等待，我們對我們在頂線看到的情況感到非常鼓舞。我無法準確評論您可能會看到或可能不會看到的內容。我認為我們必須為此等待 CTAD。

Your next question comes from Brian Skorney with Baird.

你的下一個問題來自 Baird 的 Brian Skorney。

I was wondering if you could outline any broad timeline that you have for subcu lecanemab. Just wondering what the pathway looks like and then maybe you're seeking to get an initial and chronic dosing approved? Or would this be more like initially a label where you could have patients switching, who have initiated IV over a period of time? And just any learnings from your interactions with FDA on subcu to SABRE that you think might be applied as we think about this pathway going forward?

我想知道你是否可以概述你對 subcu lecanemab 的任何廣泛時間表。只是想知道途徑是什麼樣的，然後也許您正在尋求獲得批准的初始和長期劑量？或者這更像是最初的標籤，您可以讓患者在一段時間內開始靜脈注射？從你與 FDA 就 subcu 到 SABRE 的互動中學到的任何知識，你認為在我們考慮這條途徑前進時可能會應用嗎？

Thank you, Brian. So overall, what I can tell you is that this is a very important part of the long-term comprehensive clinical development plan for lecanemab. And the subcutaneous formulation development has -- is already being pursued in the Phase III open-label extension. We're also -- Eisai is also engaging with FDA. So there's lots of discussions ongoing. I would just say that the Phase I bioavailability data has already been shared publicly. So I already shared that. And as I mentioned in my remarks, they are currently looking at the 720-milligram weekly fixed dosing and this is being evaluated.

謝謝你，布萊恩。所以總的來說，我可以告訴你的是，這是 lecanemab 長期綜合臨床開發計劃中非常重要的一部分。皮下製劑的開發已經——已經在 III 期開放標籤擴展中進行。我們也是——衛材也在與 FDA 合作。因此，正在進行很多討論。我只想說，第一階段的生物利用度數據已經公開分享。所以我已經分享了。正如我在發言中提到的，他們目前正在研究每週 720 毫克的固定劑量，並且正在對此進行評估。

But the timelines and the details of what else the package might need that has not been shared. And so I would say just let's wait for that to be shared and we will share that when it's appropriate. But it is a very important endeavor and it is ongoing.

但是尚未共享的時間表和軟件包可能還需要什麼的詳細信息。所以我想說讓我們等待共享，我們將在適當的時候共享它。但這是一項非常重要的努力，並且正在進行中。

Your next question comes from Michael Yee with Jefferies.

你的下一個問題來自 Jefferies 的 Michael Yee。

Going back to the comments about CMS reimbursement and having to wait for CTAD data, I guess maybe you could talk about what pathways or what types of interactions, if any, or what approach you can have with CMS to push urgency, whether that'd be patient advocacy groups, whether you guys are working hard to do that or whether they just see that there's a clearly a change from the ADUHELM situation a year ago and they will act fast.

回到關於 CMS 報銷和不得不等待 CTAD 數據的評論，我想也許你可以談談什麼途徑或什麼類型的互動，如果有的話，或者你可以用 CMS 採取什麼方法來推動緊迫性，無論那是倡導團體要有耐心，無論你們是在努力做到這一點，還是他們只是看到與一年前的 ADUHELM 情況相比有了明顯的變化，他們都會迅速採取行動。

So Eisai has the lead in engaging regulators and payers. And from what we know is that Eisai has already initiated engagement with CMS. So they're responsible for this activity. And at this stage, I will not provide more details. But the engagement is there, which is the most important.

因此，衛材在與監管機構和付款人接洽方面處於領先地位。據我們所知，衛材已經開始與 CMS 合作。所以他們負責這項活動。在這個階段，我不會提供更多細節。但參與是存在的，這是最重要的。

We'll go next to Robyn Karnauskas with Truist Securities.

我們將與 Truist Securities 的 Robyn Karnauskas 一起去。

My question is 2-fold. So we're hearing a lot that Lilly has a very big presence right now and mind share of doctors in this space. And you mentioned, Mike, that you tend to be -- that you think that we'll have more -- I'm trying to interpret what you said, is that you're going to ramp up spend in line with revenue. Can you just elaborate a little bit there? Because you will have competitors in this space. And a small question for Priya. We also hear that tau pathology that you may not want to do trials in patients that already have a beta plaque with tau, a couple of questions there.

我的問題是 2 倍。因此，我們經常聽到禮來（Lilly）公司現在擁有非常大的影響力，並且在這個領域的醫生中佔有一席之地。邁克，你提到你傾向於——你認為我們會有更多——我試圖解釋你所說的，你會根據收入增加支出。你能在那裡詳細說明一下嗎？因為在這個領域你會有競爭對手。還有一個小問題要問 Priya。我們還聽說 tau 病理學，你可能不想在已經有 tau β 斑塊的患者身上進行試驗，這裡有幾個問題。

Yes. I'll just clarify the point that I made before. As Eisai develops the commercialization strategy along with us, the goal there, obviously, the first and primary goal will be to get the launch right and put an infrastructure in place that supports the best launch possible and we'll be in position. And obviously, in the situation that we had with ADUHELM when we received approval in June of 2021, we had a large infrastructure that was built up and ready to go. And then obviously, we encountered significant delays.

是的。我只是澄清一下我之前提出的觀點。隨著衛材與我們一起制定商業化戰略，那裡的目標顯然是首要目標，即正確啟動並建立支持最佳啟動的基礎設施，我們將就位。顯然，在我們於 2021 年 6 月獲得批准時與 ADUHELM 的情況下，我們擁有一個已經建立並準備就緒的大型基礎設施。然後很明顯，我們遇到了嚴重的延誤。

And the point that I was making is that we would hope that, that wouldn't be a repeat and that we would have the appropriate infrastructure to support a successful launch. That's priority one. And then hopefully, we wouldn't experience delays like that. And so that you would see a spend that would ramp in front of revenue, but it wouldn't have the gap that it did on ADUHELM.

我要表達的意思是，我們希望這不會重演，並且我們將擁有適當的基礎設施來支持成功發布。這是第一要務。然後希望我們不會遇到這樣的延遲。因此，您會看到支出會在收入之前增加，但不會像在 ADUHELM 上那樣存在差距。

And I can add to that, Robyn. Thanks, Mike. I can add to that. In terms of doctors and mind share, I think that, obviously, this is a very highly rapidly evolving space from a scientific perspective, and I think lecanemab has demonstrated that removal of the plaque can result in a clinical impact. And this is really going to be important. I'd also like to add that the safety profile is going to be really, really important here. For example, with lecanemab, we've got rates of ARIA that are about 21%. We've seen this to be within expectations.

我可以補充一點，羅賓。謝謝，邁克。我可以補充一點。就醫生和思想分享而言，我認為，顯然，從科學的角度來看，這是一個非常快速發展的空間，我認為 lecanemab 已經證明去除斑塊可以產生臨床影響。這真的很重要。我還想補充一點，安全資料在這裡真的非常重要。例如，對於 lecanemab，我們的 ARIA 率約為 21%。我們已經看到這在預期之內。

And I think that this, together with the efficacy results, are going to be important for doctors to consider. So overall, while I think the question was a little bit more maybe about the launch, I would say that the mind share will depend on the data. And I think the data needs to be seen from the other anti-amyloid therapies before we decide what is going to be meaningful. The other piece I think here is, we see ourselves as pioneers. We've got this very encouraging data. We think that this is a very broad and complex patient population and the need and unmet need is very, very high.

我認為，這一點以及療效結果對於醫生來說非常重要。所以總的來說，雖然我認為問題可能更多地與發布有關，但我會說思想分享將取決於數據。而且我認為在我們決定什麼是有意義的之前，需要從其他抗澱粉樣蛋白療法中查看數據。我認為這裡的另一點是，我們將自己視為先驅。我們得到了非常鼓舞人心的數據。我們認為這是一個非常廣泛和復雜的患者群體，需求和未滿足的需求非常非常高。

So we think it's a very important place where we can really make a difference to patients. And then Robyn, on the second question, can you please clarify that? I didn't quite catch it. You broke up towards the end.

所以我們認為這是一個非常重要的地方，我們可以真正為患者帶來改變。然後 Robyn，關於第二個問題，你能澄清一下嗎？我沒聽清楚。你們分手到最後。

Yes, sorry. So for tau pathology, some scientists believe that you want to clear plaque before you give the tau. So in other words, tau may not work alone. You may need to actually combine it with lecanemab, now that we understand the biology. The thoughts on all these trials that are ongoing, including 080, like how -- do you think that there is a chance that they may not work because you actually need to actually clear plaque with an Abeta drug like lecanemab?

是的，對不起。所以對於 tau 病理學，一些科學家認為在給予 tau 之前要清除斑塊。所以換句話說，tau 可能無法單獨工作。既然我們了解了生物學，您可能需要實際將它與 lecanemab 結合起來。關於所有這些正在進行的試驗的想法，包括 080，比如——你認為它們有可能不起作用嗎，因為你實際上需要用像 lecanemab 這樣的 Abeta 藥物來清除牙菌斑？

Got it. So I think I'll just step back to say that obviously, amyloid pathology is very key. We also believe that it's potentially upstream of tau pathology. And with aducanumab with -- our data with aducanumab, we did show the impact on phosphorylated tau and such. So we think that this cascade overall is going to be very important.

知道了。所以我想我會退後一步說，顯然，澱粉樣蛋白病理學非常關鍵。我們還認為它可能是 tau 病理學的上游。對於阿杜卡單抗——我們與阿杜卡單抗的數據，我們確實顯示了對磷酸化 tau 等的影響。所以我們認為整個級聯將非常重要。

Having said that, I think that you're right, that maybe the future of Alzheimer's disease is going to be about the timing of intervention, which I already spoke to, and that's a very different matter. But it could also be that one type of approach may not be adequate. The question here is that we're trying to be very systematic and methodical in how we approach it. So we've now demonstrated with lecanemab that really there is the removal of aggregated plaque, which results in clinical impact. And I think Eisai has also shared earlier this year that this could result, with based on data from Phase IIb and modeling, that this could result in a preservation of about 2 to 3 years before patients progress to significantly more severe stages of Alzheimer's. This is based on modeling and data from Phase II. And I know that they have said publicly that they will also do this type of analysis with the Phase III data.

話雖如此，我認為你是對的，也許阿爾茨海默病的未來將與乾預的時機有關，我已經談過，這是一個非常不同的問題。但也可能是一種方法可能不夠用。這裡的問題是，我們正在努力以非常系統和有條理的方式處理它。所以我們現在已經用 lecanemab 證明了確實可以去除聚集的斑塊，這會產生臨床影響。我認為 Eisai 今年早些時候也曾分享過，根據 IIb 期和建模的數據，這可能會導致在患者進展到更嚴重的阿爾茨海默氏症階段之前保存約 2 至 3 年。這是基於第二階段的模型和數據。我知道他們已經公開表示他們也會對 III 期數據進行此類分析。

So I think that we are making significant progress. And then separately, we are tackling the BIIB080, which we had very encouraging results from our Phase Ib trial where we showed a dose and time-dependent reduction of tau. And we believe it addresses all forms of tau. So now we're in the process of initiating a Phase II. But you're absolutely right. We will be looking at many different approaches in how we can benefit patients in the best way that we can. So yes, all biologies need to be considered, but we need to go step wise, and we need to be systematic about this.

所以我認為我們正在取得重大進展。然後單獨地，我們正在處理 BIIB080，我們從我們的 Ib 期試驗中獲得了非常令人鼓舞的結果，我們顯示了 tau 的劑量和時間依賴性減少。我們相信它可以解決所有形式的 tau 蛋白。所以現在我們正在啟動第二階段。但你是絕對正確的。我們將研究許多不同的方法，以盡我們所能使患者受益。所以是的，所有生物學都需要考慮，但我們需要循序漸進，我們需要對此進行系統化。

And if I may add on the mind share. The epidemiology is so large. There is so much to be built in terms of infrastructure that I -- we all welcome the efforts of other companies. Specifically about lecanemab, and I know that you have engaged with scientific leaders, some of you. We have engaged with scientific leaders and clinicians. I think the feedback is very positive from what we hear. And at the end of the day, it will be the efficacies at 6 months and expanded over a period of 18-month study and the safety that will make the difference between the compounds. But at this stage, we welcome every effort to prepare the market for the patients in need.

如果我可以添加思想份額。流行病學是如此之大。在基礎設施方面有太多需要建設的地方，我們都歡迎其他公司的努力。特別是關於 lecanemab，我知道你已經與科學領導者進行了接觸，你們中的一些人。我們與科學領袖和臨床醫生進行了接觸。我認為從我們聽到的反饋來看，反饋是非常積極的。歸根結底，這將是 6 個月時的功效，以及在 18 個月的研究期間擴展的功效，以及將在化合物之間產生差異的安全性。但現階段，我們歡迎一切努力為有需要的患者準備市場。

Your next question comes from Jay Olson with Oppenheimer.

你的下一個問題來自 Jay Olson 和 Oppenheimer。

Congrats on the Clarity AD results. I'm curious about the potential for your collaboration with Denali and how you plan to leverage their TV platform for Abeta antibodies, including lecanemab and ADUHELM. Now that we have positive clear DAD results, do you think better brain penetration could improve the therapeutic profile of Abeta antibodies? And what is the timeline to nominate a candidate from the TV program?

祝賀 Clarity AD 結果。我很好奇您與 Denali 合作的潛力，以及您計劃如何利用他們的 Abeta 抗體電視平台，包括 lecanemab 和 ADUHELM。既然我們有了明確的 DAD 結果，您認為更好的腦滲透可以改善 Abeta 抗體的治療效果嗎？從電視節目中提名候選人的時間表是什麼時候？

Thank you, Jay. It's a very good question. What I can share with you is that we are looking across our portfolio, and we're looking at several of our existing partnerships to see how we can actually move and build on the strength of these data and the strength of the biological hypothesis that we've seen. I can't comment more specifically on the Denali TV platform. But yes, everything is on the table. We'll be looking at everything very carefully and we'll make announcements as they become relevant and as it's appropriate. Thank you.

謝謝你，傑伊。這是一個很好的問題。我可以與您分享的是，我們正在審視我們的投資組合，我們正在審視我們現有的幾個合作夥伴關係，以了解我們如何才能真正移動和建立這些數據的力量以及我們認為的生物學假設的力量'已經看到。我無法在 Denali TV 平台上更具體地發表評論。但是，是的，一切都擺在桌面上。我們將非常仔細地研究所有內容，並在它們變得相關且適當時發佈公告。謝謝你。

We'll go next to Phil Nadeau with Cowen and Company.

我們將與 Cowen and Company 一起去 Phil Nadeau。

A follow-up question on the learnings from the aducanumab launch. What are Biogen's recent thoughts on lecanemab's price? Would you expect to price at a premium to ADUHELM because of better data, a discount because of the pushback? And appreciating that Eisai has final say on all commercialization decisions, what role will Biogen play in setting the price of lecanemab?

關於從 aducanumab 發布中學到的知識的後續問題。百健（Biogen）最近對 lecanemab 的價格有何看法？您是否會因為更好的數據而以高於 ADUHELM 的價格定價，或者因為阻力而定價？鑑於衛材對所有商業化決策擁有最終決定權，百健（Biogen）將在設定 lecanemab 的價格方面發揮什麼作用？

As you can anticipate, we cannot comment. It's Eisai's decision and we will not interfere with this process.

如您所料，我們無法發表評論。這是衛材的決定，我們不會干涉這個過程。

We'll go next to Marc Goodman with SVB Securities.

我們將與 SVB Securities 一起去 Marc Goodman 旁邊。

Could you give us a little more color on OUS SPINRAZA, just what the dynamics were? Something about price increases or positive pricing dynamics there? And then just, Priya, can you just confirm, is the subcu dose 720 weekly, is that the one that we're going to be using? Or we're still working on the dosing regimen?

你能給我們更多關於 OUS SPINRAZA 的顏色嗎，動態是什麼？關於價格上漲或積極的定價動態？然後，Priya，你能否確認一下，每周亞劑量 720 次，這是我們要使用的嗎？或者我們仍在研究劑量方案？

I think your question was about ex U.S. SPINRAZA. Yes, so we see 2 types of dynamic. We see a European momentum that is being slowed down by the launch of risdiplam. But we are sharing data on the switch from patients, patients from the U.S. from risdiplam back to SPINRAZA for efficacy reason. So I think -- and we are learning from the U.S. So it's a matter of time. We are learning from the U.S. We're delighted by the U.S. results. And we believe that this becomes a model for what other continents should learn from. And ex core Europe, we see a very rapid growth in terms of volume, but the price is not the same.

我認為您的問題是關於前美國 SPINRAZA 的。是的，所以我們看到兩種類型的動態。我們看到 risdiplam 的推出正在減緩歐洲的勢頭。但我們正在分享來自美國的患者出於療效原因從 risdiplam 轉回 SPINRAZA 的數據。所以我認為——我們正在向美國學習，所以這是一個時間問題。我們正在向美國學習。我們對美國的結果感到高興。我們相信，這將成為其他大陸應該學習的榜樣。在核心歐洲之外，我們看到數量增長非常迅速，但價格卻不一樣。

So this is the momentum ex U.S. Overall, we are delighted by the U.S. results where we can see SPINRAZA coming back and we believe the product will resume its momentum to growth gradually. Mike, do you want to add?

所以這是美國以外的勢頭總的來說，我們對美國的結果感到高興，我們可以看到 SPINRAZA 回歸，我們相信該產品將恢復其逐漸增長的勢頭。邁克，你想補充嗎？

Yes. I would just add, and in the spirit of your question, Marc, was directed more at OUS. We mentioned the U.S. was flat. And OUS. overall, there was a modest decline. But if you strip out FX on a constant currency basis, there was actually growth and that growth to the points that we made in our prepared remarks, there was a modest volume decline primarily due to competition in places like Germany and Canada and Japan, and we had some timing items, Russia, Brazil, few others, which was partially offset by volume growth in China.

是的。我只想補充一點，根據您的問題精神，Marc 更多地針對 OUS。我們提到美國持平。還有我們。總體而言，下降幅度不大。但是，如果你在固定匯率的基礎上剔除外匯，實際上是有增長的，而且這種增長達到了我們在準備好的發言中提出的要點，但由於德國、加拿大和日本等地的競爭，交易量略有下降，而且我們有一些時間項目，俄羅斯，巴西，其他一些，這部分被中國的銷量增長所抵消。

But we did have price increases in a few of our markets throughout Europe that, that more than offset the volume. So to kind of unpack it, you had modest volume declines slightly more than offset by price increases and then you had the FX going against OUS.

但我們在整個歐洲的一些市場確實出現了價格上漲，這遠遠抵消了銷量。因此，為了某種程度上打開它，你有適度的成交量下降略微超過價格上漲所抵消的，然後你有 FX 對 OUS。

And I'll just wrap up really quickly on the second point. I think that you -- second question you had, Eisai has communicated that the 720-milligrams weekly fixed dose is the dose that show the equivalence to intravenous dosing, 10-milligram per kg biweekly. And it's also actually now listed for the auto-injector study that was recently announced. I think that was the question. Please correct me if you had a different point in mind. Thank you.

我將很快結束第二點。我認為你——你的第二個問題，Eisai 已經表示，每週 720 毫克的固定劑量是顯示與靜脈給藥等效的劑量，每兩週 10 毫克每公斤。而且它現在實際上也被列為最近宣布的自動注射器研究。我想這就是問題所在。如果您有不同的想法，請糾正我。謝謝你。

We'll go next to Chris Schott with JPMorgan.

我們將與摩根大通的克里斯肖特一起去。

Can you just talk a little bit more around the dynamics about the 2-week IV therapy for lecanemab as we wait for the subcu and maintenance programs? I guess, reimbursement aside, how challenging do you think this is going to be from a commercial and infrastructure standpoint? And I know you're not talking about timing, but is this a relatively short window that you envision that will be using this current dosing paradigm or could be dealing with this for an extended period of time?

在我們等待 subcu 和維護計劃時，你能多談談關於 lecanemab 的 2 週 IV 治療的動態嗎？我想，拋開報銷不談，從商業和基礎設施的角度來看，您認為這將具有多大的挑戰性？而且我知道你不是在談論時間，但這是一個相對較短的窗口，你設想將使用當前的劑量範式，還是可以在更長的時間內處理這個問題？

Okay. So I think overall, we've seen very good data with the 10-milligram per kg biweekly dose. I think the important point that is very, very, I think, relevant here is that the separation is seen at 6 months, as early as 6 months, there's no titration and that expands on an absolute basis until the 18-month primary endpoint readout in Clarity AD. So this is very encouraging data.

好的。所以我認為總的來說，我們已經看到了非常好的每公斤兩週劑量 10 毫克的數據。我認為這裡非常非常重要的一點是，分離在 6 個月時就可以看到，早在 6 個月，沒有滴定，並且在絕對基礎上擴展，直到 18 個月的主要終點讀數在 Clarity AD 中。所以這是一個非常鼓舞人心的數據。

I would say that as the infrastructure around Alzheimer's disease and all of this has been built out, it will actually be quite important for patients to be seen by physicians. So we don't see it necessarily as a disadvantage, if that was the question. We don't see it as a disadvantage. But having said that, we are doing everything. Eisai is leading this effort, and we're trying to make sure that we are keeping patient convenience in mind, which is the premise of the subcutaneous development. So I can't comment beyond that on how long it will be intravenous and when would it transition to subcutaneous. But we're looking at all these aspects very carefully at a high level and also at a granular level as we build out the clinical development program with all these topics in mind.

我要說的是，隨著阿爾茨海默氏病的基礎設施和所有這一切都已經建成，對患者來說，醫生看病實際上非常重要。因此，如果這是個問題，我們並不認為它一定是一個劣勢。我們不認為這是一個缺點。但話雖如此，我們正在做一切。衛材正在領導這項工作，我們正在努力確保牢記患者的便利，這是皮下開發的前提。所以我不能就靜脈注射多長時間以及何時過渡到皮下注射發表評論。但是，當我們在考慮所有這些主題的情況下構建臨床開發計劃時，我們正在從高層次和細粒度層面非常仔細地研究所有這些方面。

So overall, we believe in the early stages, it will actually be really important for patients to be seen in the clinic every 2 weeks.

所以總的來說，我們相信在早期階段，每 2 周到診所看一次患者實際上非常重要。

Your next question comes from Paul Matteis with Stifel.

你的下一個問題來自 Stifel 的 Paul Matteis。

Great. I was wondering, based on your experience in the field with ADUHELM, how would you characterize infusion capacity today in neurology clinics ahead of the lecanemab launch? Where is it today? And how much ramp up do you think needs to happen for there to be materially broader access over time?

偉大的。我想知道，根據您在 ADUHELM 領域的經驗，在 lecanemab 推出之前，您如何描述當今神經病學診所的輸液能力？今天在哪裡？您認為需要增加多少才能隨著時間的推移在實質上更廣泛地訪問？

So what we saw for ADUHELM is that the system has shown some adaptability by shifting some of the existing infusion center to a potentially ADUHELM at that time should there be a reimbursement. We never got reimbursement, so this never happened. And overall, I believe there is a need to upscale and the capacity has to be much larger. But from our learning, we could see that the system was flexible and adaptable based on the current capacity.

因此，對於 ADUHELM，我們看到的是該系統通過將一些現有的輸液中心轉移到潛在的 ADUHELM 而顯示出一定的適應性，當時應該有報銷。我們從未得到報銷，所以這從未發生過。總的來說，我認為需要升級，容量必須大得多。但是從我們的學習中，我們可以看到該系統是靈活的，並且可以根據當前的容量進行調整。

Your next question comes from Geoff Meacham with Bank of America.

你的下一個問題來自美國銀行的 Geoff Meacham。

Just a follow-up on lecanemab launch spending. Post the restructuring that you guys had earlier this year, can you talk a little bit about the manufacturing assets that you can redeploy or maybe some of the commercial investments that you made for ADUHELM that can be reallocated for the lecanemab launch? I'm just trying to get a sense for kind of the magnitude of the spend versus the adoption over the course of next year.

只是對 lecanemab 啟動支出的跟進。在你們今年早些時候進行的重組之後，你們能否談談你們可以重新部署的製造資產，或者你們為 ADUHELM 所做的一些商業投資，這些投資可以重新分配用於 lecanemab 的發布？我只是想了解一下明年的支出規模與採用率之間的關係。

Mike?

麥克風？

Yes. So a couple of comments, Geoff. Thanks for the question. I would say first on manufacturing, we have a significant facility in Raleigh, North Carolina and then we have a relatively new facility in Solothurn, Switzerland. And the Solothurn, Switzerland facility will be largely dedicated to our Alzheimer's disease products, which for now involves a ramp-up of getting inventory ready for launch for lecanemab. I think we had a little over $100 million of inventory on hand as of the end of the quarter. And the -- that facility, its efficiency, so to speak, is heavily tied to the lecanemab launch.

是的。 Geoff，有幾點意見。謝謝你的問題。我首先要說的是製造，我們在北卡羅來納州的羅利有一個重要的工廠，然後我們在瑞士的索洛圖恩有一個相對較新的工廠。瑞士 Solothurn 工廠將主要致力於我們的阿爾茨海默病產品，目前包括增加庫存，為 lecanemab 的發布做好準備。我認為截至本季度末，我們手頭的庫存略多於 1 億美元。而且——那個設施，它的效率，可以說，與 lecanemab 的推出密切相關。

And then to the extent that ADUHELM becomes more marketable, we could utilize that facility as well. So that's the state of play there. There will be some idle capacity. You saw about $12 million this quarter. There'll be some idle capacity charges that we'll have to incur over time as that product ramps. I would say on the commercial infrastructure, there's not a lot that can or will be repurposed from ADUHELM. We did make the decision, as we've said before, to take that infrastructure down. It was just too long of a time gap from the time that we received the NCD in April of 2022 to when lecanemab would become fully commercialized to maintain that infrastructure.

然後，如果 ADUHELM 變得更有市場，我們也可以利用該設施。這就是那裡的遊戲狀態。會有一些閒置產能。本季度您看到了大約 1200 萬美元。隨著時間的推移，隨著產品的增加，我們將不得不承擔一些閒置容量費用。我想說的是，在商業基礎設施方面，ADUHELM 可以或將會重新利用的東西並不多。正如我們之前所說，我們確實做出了拆除該基礎設施的決定。從我們在 2022 年 4 月收到 NCD 到 lecanemab 完全商業化以維護該基礎設施的時間間隔太長了。

So most of that's been eliminated as part of our $1 billion cost savings that we've committed. And so for the most part, the lecanemab commercialization will be a new ramp and a new infrastructure that will be built.

因此，作為我們承諾的 10 億美元成本節約的一部分，其中大部分已被消除。因此，在大多數情況下，lecanemab 的商業化將是一個新的斜坡和一個將要建造的新基礎設施。

And that concludes our call for this morning. Thank you, everyone, for joining us.

我們今天上午的呼籲到此結束。謝謝大家加入我們。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。