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)

早安.我叫詹妮弗，今天我將擔任您的會議主持人。現在，我歡迎大家參加 Biogen 2022 年第三季財報電話會議和業務更新。 （操作員指令）

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。現在，我想將會議交給投資者關係主管 Mike Hencke 先生。亨克先生，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，歡迎參加 Biogen 2022 年第三季財報電話會議。在我們開始之前，我鼓勵大家去 biogen.com 的投資者部分查找收益報告和相關財務表，包括我們的 GAAP 財務指標以及我們今天將討論的 GAAP 與非 GAAP 財務指標的對帳。我們的 GAAP 財務資料在表 1 和表 2 中提供，表 4 包括我們的 GAAP 與非 GAAP 財務結果的對帳。

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.

我們相信非公認會計準則財務結果能更能反映我們業務的持續經濟狀況並反映我們如何進行內部業務管理。我們也在我們的網站上發布了有關本次電話會議討論的幻燈片。我想指出的是，我們將做出前瞻性的陳述，這些陳述是基於我們目前的預期和信念。這些聲明受某些風險和不確定性的影響，我們的實際結果可能存在重大差異。我鼓勵您查閱我們提交給美國證券交易委員會的文件中討論的風險因素，以獲取更多詳細資訊。

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，我們的執行長 Michel Vounatsos 也與我一起出席； Priya Singhal 博士，臨時研究與發展主管；以及我們的財務長 Mike McDonnell。 （操作員指示）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.

大家早安，感謝大家的收看。對於 Biogen 來說，這是一個令人興奮的時刻。除了我們整個產品線的關鍵進展（包括處於第三階段或已提交的 12 個項目）之外，我們還將繼續推進進展，並且很高興能夠提高全年財務指導。

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.

首先，我想回顧一下我們本季取得的重要進展以及我們認為它們對 Biogen 的意義。然後，Priya 將回顧我們在研發方面的最新進展，Mike 將討論我們第三季的業績。首先，我們與衛材一起高興地宣布 lecanemab 治療早期阿茲海默症的 III 期研究 CLARITY AD 取得了積極成果。 15 年來，Biogen 一直不懈地致力於開發阿茲海默症的新治療方法，結合疾病生物學和臨床試驗設計的新見解。

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 CLARITY AD 的積極讀數，這是阿茲海默症治療領域的重大成就。 Clarity AD 的結果說明了 lecanemab 臨床特徵的幾個關鍵方面，我們相信這可以為患者帶來有意義的益處。首先，lecanemab 治療早在 6 個月內就顯示出臨床衰退的高度統計學顯著減少，並且在 18 個月的研究期內絕對值擴大，與疾病改良作用一致。

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，該研究對所有關鍵次要終點均表現出正面結果。這包括認知能力的測量以及日常生活活動，例如管理個人財務、執行家務和獨立出門旅行。第三，Clarity AD 內的 ARIA 率符合預期。預計 FDA 將於明年 1 月 6 日做出加速批准決定，而衛材計劃於 2023 年第一季末在美國、歐盟和日本提交傳統批准，因此 lecanemab 有可能成為全球首個獲批的減緩阿茲海默症進展的治療方法。

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，繼續與監管機構和 CMS 合作，以確保阿茲海默症患者能夠獲得重要的新治療方法。我們相信 Clarity AD 的結果強調了我們在對抗阿茲海默症方面的進展。但 Biogen 不會就此止步。我們計劃在現有知識的基礎上繼續推進多樣化的潛在阿茲海默症治療管道。這包括兩種針對 tau 病理的臨床階段資產，BIIB080（我們已準備好進入 II 期的反義寡核苷酸）和 BIIB113（一種 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.

除了阿茲海默症之外，Biogen 在其他治療領域也擁有重要機會，這些領域尚未滿足的醫療需求仍然很大。這包括憂鬱症，我們將與 Sage 一起繼續推進 zuranolone 在重度憂鬱症和產後憂鬱症方面的監管備案。由於其具有新穎的作用機制、最早在 3 天內觀察到的療效以及 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，zuranolone 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 已根據加速審批途徑接受了我們關於 SOD1-ALS 藥物 tofersen 的申請，並給予優先審查。雖然研究在 6 個月時沒有達到主要終點，但更長的追蹤顯示，繼續使用 tofersen 的患者的肺功能、肌肉力量和生活品質等關鍵臨床指標的下降速度緩慢。對於這種使人衰弱和致命的疾病，這些結果確實讓我們感到鼓舞，我們期待 FDA 於明年 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，這些短期機會以及生物相似藥的新推出，有可能推動新的成長，並使我們在 2025 年前擁有 5 個關鍵特許經營權。總的來說，我們相信我們正處於中樞神經系統藥物發現和開發的轉折點。這些最新發展體現了神經科學領域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，Biogen 一直致力於拓展我們在該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先地位，因為我們致力於迎接中樞神經系統治療的新浪潮，同時推進我們在專門免疫學領域的產品組合，我們在狼瘡領域有 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.

現在，我將把電話轉給 Priya，讓她更詳細地介紹我們最近在研發方面的進展。

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，大家早安。正如米歇爾所提到的，我們上個季度取得了幾項令人興奮的研發成果，這些成果極大地提升了我們產品線的潛力，其中包括 30 個項目，其中 12 個項目處於 III 期或已提交申請，旨在為患者提供新的有效治療方法並推動公司新的增長。

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%.

從阿茲海默症開始。我們與衛材一起非常高興地宣布了 Clarity AD 研究的積極成果，該研究評估了 lecanemab 在早期阿茲海默症中的應用。研究的主要終點是 CDR-Sum of Boxes 相對於基線的變化，CDR-Sum of Boxes 是阿茲海默症的認知和功能完善的測量方法。該研究達到了主要終點，與 18 個月時的安慰劑相比，lecanemab 將 CDR-Sum of Boxes 的臨床下降減少了 0.45，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.

我們也觀察到，與安慰劑相比，早在 6 個月時，CDR-Sum of Boxes 就出現了具有高度統計意義的顯著下降。我們相信這表明療效迅速顯現，並且與安慰劑相比，CDR-Sum of Boxes 發生了顯著變化。此外，在 18 個月的研究期內，對 CDR-Sum of Boxes 的影響在絕對基礎上擴大，顯示 lecanemab 正在發揮改善疾病的作用。

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.

研究也滿足了所有關鍵的次要終點，強化了 lecanemab 對認知和功能的影響。這包括腦內澱粉樣蛋白斑塊的統計顯著減少，以及其他臨床評估，如 ADCS-MCI-ADL，這是相對於安慰劑的護理人員評估的日常生活活動評估。我們相信，這些療效結果與觀察到的約 21% 的 ARIA 總體發病率相結合，凸顯了 lecanemab 成為阿茲海默症的主要疾病改良治療方法的潛力。

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 的研究結果，並打算在同行評審的醫學期刊上發表研究結果。加速審批途徑下的 lecanemab 申請目前正在審查中，PDUFA 日期為 2023 年 1 月 6 日。 FDA 也同意 Clarity AD 可以作為確認性研究，以驗證 lecanemab 的臨床益處。因此，我們預計，在 FDA 做出加速批准的積極決定後，衛材將盡快在美國申請 lecanemab 的傳統批准。預計該文件將於 2023 年第一季末提交，同時歐盟和日本的營銷授權申請也預計將於 2023 年第一季末提交。

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.

衛材也一直與醫療保險和醫療補助服務中心合作，致力於最大限度地為患者提供醫療服務。除了這些監管和准入合作之外，我們還與衛材一起推進了 lecanemab 的全面開發計劃，其中包括首先，正在進行的 AHEAD 3-45 臨床前研究，以評估在疾病早期（即出現澱粉樣蛋白病理但在認知障礙出現之前）使用 lecanemab 的效果。

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。以及lecanemab皮下製劑的開發。今年早些時候，衛材在 AAIC 上展示了 I 期研究的生物利用度數據，該研究比較了靜脈注射和皮下注射給藥，以及建模和模擬數據，表明每週固定皮下劑量 720 毫克可能產生與當前靜脈注射製劑相當的暴露量和療效，同時可能降低 ARIA 的發病率。

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.

有了這些成果，我們現在專注於長期保持我們在阿茲海默症領域的領導地位。我們擁有業界領先的針對澱粉樣蛋白和 tau 病理的產品組合，以及針對廣泛阿茲海默症生物學的多目標、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 提供了新的數據，支持 zuranolone（如果獲得批准）作為重度憂鬱症和產後憂鬱症的新治療方法的潛力。這包括對 MDD 中正在進行的開放標籤縱向 SHORELINE 研究的最新分析，該顯示，首次發病的中位數時間——對不起，對於對最初的 14 天治療有反應的患者，首次重複治療的中位數時間為 30 毫克組 135 天，50 毫克組 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了 zuranolone 作為憂鬱症患者一種潛在且有意義的新治療方法。我們將繼續與 Sage 合作，推動 zuranolone 在 MDD 和 PPD 治療領域的單一美國監管備案，預計今年年底完成。

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.

繼續討論我們的神經肌肉組合。 《新英格蘭醫學雜誌》最近發表了 III 期 VALOR 研究及其開放標籤擴展研究的 12 個月數據，該研究評估了 tofersen 對 SOD1-ALS 的療效，SOD1-ALS 是一種漸進性和罕見的遺傳性 ALS，目前尚無針對性治療方法。已發表的數據顯示，與 6 個月後開放標籤擴展開始時從安慰劑轉為使用 tofersen 的患者相比，在 VALOR 中開始使用 tofersen 的患者在功能、肌肉力量和生活品質等關鍵指標方面的下降速度較慢。

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（神經元損傷和神經退化的標誌）強烈且持續地減少。 7月份，tofersen的申請根據優先審查的加速審批途徑被FDA接受。隨後，我們提交了對FDA資訊請求的回應，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，FDA 預計將於 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 合作啟動了小分子 LRRK2 抑制劑 BIIB122 的第二次後期臨床試驗。第三階段 LIGHTHOUSE 研究將評估 BIIB122 對確診致病 LRRK2 突變個體的作用。鑑於 LRRK2 活性被認為可以調節溶小體功能和與帕金森氏症有關的潛在生物學途徑，我們也正在推進今年稍早啟動的特發性帕金森氏症 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.

轉向專門的免疫學。我們很高興地宣布啟動利替利單抗或 BIIB059 治療皮膚紅斑狼瘡 (CLE) 的 II/III 期研究。先前進行的利替利單抗 II 期 LILAC 研究達到了研究兩個部分的主要終點，評估了該藥物對 CLE 和系統性紅斑狼瘡 (SLE) 患者的安全性和有效性。第二階段的詳細結果最近作為兩份獨立的手稿發表在《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 期研究建立在我們專門免疫學的中後期管線之上，其中還包括 3 項 SLE 的 III 期研究，其中 2 項為利替利單抗，1 項為達匹羅珠單抗，這些研究都是我們與 UCB 合作開發的。

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，我們也面臨許多令人興奮的機會。這包括在阿茲海默症、憂鬱症和 SOD1-ALS 方面提供新療法的潛力、啟動阿茲海默症和中風的中後期計畫以及在廣泛的 ALS 中進行概念驗證研究。

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，我們相信我們最近的進展體現了 Biogen 更廣泛的研發方法的重要組成部分。這包括專注於經過基因驗證的標靶和生物學、使用新型生物標記來更好地表徵疾病生物學和標靶參與，以及我們針對特定疾病區域或標靶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.

總之，我們相信，這些原則加上我們正在進行的優先排序努力，有可能提高在存在重大未滿足需求的疾病領域取得成功的機率。我現在將電話轉給麥克。

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，大家早安。我將介紹我們第三季的財務業績亮點以及 2022 年全年指引的最新情況。請注意，所有財務比較均與 2021 年第三季進行比較。

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.

第三季總營收為 25 億美元，以實際匯率計算下降 10%，以固定匯率計算下降 8%。 第三季非 GAAP 攤薄每股收益為 4.77 美元，與 2021 年第三季持平。

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 全球營收為 3.39 億美元，以實際匯率計算下降 32%，以固定匯率計算下降 30%。我們看到 TECFIDERA 在美國市場因仿製藥而持續下滑，也受到美國以外地區（主要是德國）仿製藥的影響。我們不斷看到歐盟推出新的仿製藥。本月初，歐洲法院總檢察長發表了一份不具約束力的諮詢意見。如果法院採納該諮詢意見，我們預計 TECFIDERA 至少在 2024 年 2 月之前將受到法定市場保護。法院發布最終裁決沒有最後期限，但我們了解到，通常在總檢察長意見發布後約 3 至 5 個月內做出裁決。

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，我們正在採取行動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。 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.

VUMERITY 全球營收為 1.38 億美元，以實際匯率計算成長 14%，以固定匯率計算成長 15%。美國 VUMERITY 收入因銷量增加而增長 6%，但折扣和配額的增加部分抵消了這一增長。 VUMERITY 受到付款人壓力和美國口服藥物市場萎縮的雙重影響。我們繼續與我們的合約製造供應商合作，以解決 VUMERITY 的潛在供應限制。我們已經找到了根本原因，實施了解決問題所需的製造變更，目前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 年重新啟動新國家的上市。折扣和配額增加以及銷售下降對美國 TYSABRI 的收入產生了負面影響。在美國以外，我們很高興看到患者數量持續增長以及歐盟對皮下製劑的良好接受度，該製劑目前已在超過 25 個市場推出，平均轉換率約為 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 的物質成分專利已過期，但我們擁有與 TYSABRI 的製造和使用相關的其他專利，包括我們 10-K 中列出的專利。我們將繼續執行這項智慧財產權，包括在美國對山德士提起訴訟。全球幹擾素營收為 3.36 億美元，以實際匯率計算下降 13%，以固定匯率計算下降 12%，受到從注射平台持續轉變為口服或高效療法的影響。

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.

移至 SMA。 SPINRAZA 全球營收為 4.31 億美元，以實際匯率計算下降 3%，以固定匯率計算成長 2%。在美國，SPINRAZA 的收入與上年持平，我們相信我們可能在美國看到穩定的跡象。總體而言，我們仍然相信 SPINRAZA 具有隨著時間的推移而成長的潛力。

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.

轉向我們的生物相似藥業務。營收為 1.88 億美元，以實際匯率計算下降 7%，以固定匯率計算下降 4%。我們的銷售量有所增長，但是由於不利的定價和負面的貨幣影響而被抵消。我們繼續期待 BYOOVIZ 的逐步推出，並預計在 2023 年開始帶來更有意義的收入貢獻。

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 總營收為 4.17 億美元，與前一年持平。 OCREVUS 特許權使用費收入成長了 6%，但被 RITUXAN 因生物相似藥競爭而持續下滑所抵銷。

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.

現在來討論資產負債表中的費用。第三季非公認會計準則銷售成本為 4.7 億美元，其中包括 1,200 萬美元的閒置產能費用。展望未來，我們預計，由於產品結構的變化和潛在的閒置產能費用（主要由於 ADUHELM 藥品生產的暫停），毛利率將面臨進一步的壓力。第三季非公認會計準則研發費用為 5.49 億美元。相較之下，2021 年第三季的支出為 7.02 億美元，其中包括與業務發展交易相關的約 1.65 億美元預付款以及臨床試驗結算成本。

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.

非公認會計準則銷售、一般及行政開支為 5.62 億美元。相較之下，2021 年第三季為 6.51 億美元。第三季合作利潤分享淨支出為 4,500 萬美元，主要得益於與三星 Bioepis 的合作。非公認會計準則其他費用為 5,500 萬美元，主要由利息費用構成。

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 億美元的營運現金流。資本支出為 5,900 萬美元，自由現金流為 6.02 億美元。我們在本季以 2.5 億美元的價格回購了 120 萬股公司普通股，平均價格為每股 214 美元。截至本季末，我們的現金和有價證券為 58 億美元，債務為 63 億美元，淨債務約 5 億美元。

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，第三季度，作為辦公室佔地面積優化計劃的一部分，我們透過出售位於劍橋的一棟建築獲得了 5.83 億美元的淨收益。此外，10月份，我們支付了9億美元以上的費用和開支來解決先前披露的公益訴訟。提醒一下，我們預計未來 1.5 年內將透過出售我們在三星 Bioepis 的股權獲得額外的 12.5 億美元，其中包括明年 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 億美元未使用的循環信貸額度，可用於長期投資業務成長。在介紹我們的最新指南之前，我想先談談 lecanemab。我們很高興能夠在全球 50-50 利潤分享協議下與 Eisai 合作進行這項重要合作。

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.

需要提醒的是，Biogen 有權與 Eisai 共同商業化和共同推廣 lecanemab，而 Eisai 擁有最終決策權。經批准後，我們的利潤或損失份額將作為其他收入的一部分入帳。在推出後的最初幾個季度，其他收入中的 lecanemab 部分可能為負數。請參閱我們的收益報告中的第 26 張投影片，以了解其他會計考量。

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，我來討論我們更新的 2022 年全年指引。我們將全年營收預期從先前的 99 億美元至 101 億美元上調至 100 億美元至 101.5 億美元，並將全年非 GAAP 稀釋每股收益預期從先前的 15.25 美元至 16.75 美元上調至 16.50 美元至 17.15 美元。此次指引上調主要得益於好於預期的營收表現和持續的成本管理。

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.

我們對非公認會計準則研發費用、非公認會計準則銷售、一般及行政費用和非公認會計準則稅率的指導範圍均與先前的指導相比沒有變化。提醒一下，我們通常會看到第四季的銷售、一般及行政費用 (SG&A) 支出出現季節性成長。本指南假設 9 月 30 日的外匯匯率在扣除對沖活動後將在今年剩餘時間內保持有效。本財務指引也假設，由於生物相似藥的競爭， RITUXAN 的收入將繼續下滑，而由於仿製藥的進入， TECFIDERA 的收入也將持續受到侵蝕。請參閱我們的新聞稿，以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導。我們對最近的 lecanemab 數據感到非常興奮，並相信隨著我們繼續建立多特許經營組合，我們在神經科學、專業免疫學和生物仿製藥領域的多元化管道有潛力隨著時間的推移使 Biogen 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.

像往常一樣，我們始終致力於為股東創造長期價值。現在，我們可以開始提問了。

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

（操作員指示）您的第一個問題來自 Evercore 的 Umer Raffat。

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?

我對您與衛材的關係狀況有疑問。許多投資者對此有疑問。我真的很好奇，您能否談談雙方合作關係的現狀，您是否預計衛材會允許您進行共同商業化，並且不存在任何合約糾紛或類似情況？

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?

謝謝你的提問，Umer。我可以告訴你，多年來，我們之間的關係一直非常牢固。我有機會定期與我們的同行會面並進行協調。在接下來的日子裡我還會再做一次這樣的事。該團隊正在非常緊密地合作。我們目前正在討論聯合商業化和聯合行銷事宜，但尚未確定。而且——但總體而言，這種關係是健全和牢固的。麥克，你還有什麼要補充嗎？

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，我想這就涵蓋了。我想說的是，當我們共同製定商業化策略時，衛材顯然擁有最終決策權，但利潤分成是 50-50。我們都非常期待即將舉行的 CTAD 演示，屆時我們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.

我們將討論來自 RBC Capital Markets 的 Brian Abrahams 提出的下一個問題。

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.

恭喜本季和 lecanemab 數據取得佳績。我很好奇，您如何設想透過加速批准而不是完全批准來獲得 lecanemab 的報銷管道？並且我想知道，根據您和您的合作夥伴正在進行的 CMS 討論，您對 Clarity AD 的頂線結果是否能夠滿足 CMS 的高級證據要求以支持在加速批准的情況下對 NCD 重新考慮的最新看法是什麼。

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的問題。我認為這一切都取決於證據的強度。我們對初選和複選的最高結果感到非常滿意。我們都期待 CTAD 和即將出版的出版物，以便評估 CMS 將考慮的證據等級並指明前進的道路。普里婭？

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。完全正確。我還要補充一點，NCD 中概述了幾種情況。因此，對於加速審批方案而言，它本質上只是在隨機對照試驗的情況下才被覆蓋，而這本質上是不被覆蓋的。但對於傳統的批准，我認為 NCD 指出了一系列的選擇，即它可以包含在 CMS 批准的前瞻性比較研究中，包括註冊中心。

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獲得最終傳統批准的隨機對照試驗的強度和嚴謹性。因此從這個意義上來說，我們對證據的力道非常有信心。如您所知，我們達到了主要終點，治療差異為 0.45，與安慰劑相比，使用 lecanemab 的差異為 27%。並且所有次要終點均以高度統計顯著的方式滿足。此外，我想補充一點，我們還有大約 25% 的人口代表性不足。

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.

因此我們認為它的設計非常好，而且結果非常令人鼓舞。其餘情況仍有待觀察，衛材已與 CMS 接洽討論此事。您特別詢問了重新考慮的問題，因此我只想補充一點，在 NCD 提出的最終方案中——NCD 最終提出的方案是 CMS 將採取緊急行動，並且可能會考慮重新考慮。從歷史先例來看，這可能需要 9 到 12 個月的時間。但我認為，從這個意義上來說，他們已經表示將採取緊急行動。這將是全面的覆蓋，而不需要前瞻性的比較研究。因此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.

您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?

基於 lecanemab 數據，您能否向我們介紹您對業務發展和投資組合優先順序的看法？

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，我們確實在 BD 上保持著非常活躍的狀態——評估 BD。顯然，該投資組合非常強勁。正如我們在準備好的演講中所說的那樣，我們有 12 個已提交 III 期申請的產品，並且正在為 AD、ALS、MDD 和 PPD 做準備。所以我們都很忙。儘管如此，我們仍考慮 BD，因為產品組合總是可以改進。我們每週都在評估前景，並且正在取得進展。我們在過去幾年裡達成了 30 多筆交易，但我們仍然非常活躍。 Priya 和 Mike？

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.

我認為這是一個很好的問題。退一步來說，正如米歇爾在演講中提到的，我們將自己視為阿茲海默症領域的領導者。我們相信我們已經對科學假設和生物學做了許多評估。我們已經建立了自己的投資組合，以便能夠解決從生物學角度來看的問題以及時間問題。因此我認為從生物學角度來看，我們現在在 lecanemab 方面已經取得了成功。之前，我們也看到了 aducanumab 的結果，這就是 Abeta 假設。

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，我們自己也針對 tau 進行了單株抗體的研究，但沒有效果。因此，我們確實用細胞外 tau 測試了這個假設，現在我們準備用 BIIB080 啟動第二階段的試驗，BIIB080 是一種反義寡核苷酸，可以解決所有翻譯後形式的 tau。因此我們相信（聽不清楚）我們相信我們擁有領先的反義寡核苷酸。此外，我們在第一階段推出了 BIIB113，它解決了 tau 聚集問題，並解決了 tau 聚集的酶抑制問題。

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.

因此，我們正嘗試從澱粉樣蛋白和 tau 病理學基礎等各個方面來解決這個問題。除此之外，在臨床前領域，我們也正在非常仔細地研究其他幾種生物學製劑的目標和方式。所以我認為我們有一個非常全面的方法。至於時間，我很高興我們已經在臨床前阿茲海默症中對 lecanemab 進行了測試。這是一項正在進行的研究，它將解決當你之前進行抗澱粉樣蛋白治療時會發生什麼情況——當你確實有澱粉樣蛋白聚集但沒有症狀時。

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.

所以我認為這是一種非常全面的方法。我們不會就此止步。我們繼續關注非常有吸引力的目標。我認為 BD 和內部發展將繼續發揮重要作用。最後，透過 lecanemab，我們正在測試開發計劃中的兩個非常重要的方面。衛材顯然在這方面處於領先地位。在第二階段開放標籤擴展中，我們正在研究維持劑量。那麼，繼續維持臨床衰退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.

我們正在研究第三階段開放標籤擴展中的皮下開發。所以我認為總的來說，它非常非常全面。我認為，我們將在這個領域繼續投資，以贏得勝利。謝謝。

Mike, do you want to add anything to BD?

麥克，你想為 BD 添加一些內容嗎？

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，我只想快速補充一點——我想你已經說完了，但我只想快速補充一點。您沒有看到本季 BD 以新的合作或併購的方式進行活動，您不應該對此進行任何解讀。我們繼續擁有非常強大的管道，並繼續關注各種交易。它確實趨於不穩定，你應該充分預料到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.

正如 Priya 所言，神經退化性疾病在我們的產品化過程中佔據更重要的地位。我們在 AD 領域處於領先地位，我們正在積極尋找所有我們可以收購的目標和資產，甚至更多。

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

我們將由 Wolfe Research 的 Tim Anderson 來回答您的下一個問題。

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.

我實際上對 ADUHELM 有一個疑問。這與您之前關於您在 lecanemab 中所扮演的角色仍在考慮中的評論有點相關。我想很多人都以為你們幾乎洗手不干，並沒有用 ADUHELM 做任何事。但據我所知，事實可能並非如此。您仍在尋求該產品的子版本。聽起來您可能仍在試圖尋找一種方法來讓 APOE4 攜帶者獲得 CMS 報銷。我想知道這是否屬實，以及這是否會成為與衛材之間關係緊張的根源？我只是不明白為什麼你不全力投入 lecanemab，以及為什麼你仍可能積極使用 ADUHELM。

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（聽不清楚），與我們優秀的合作夥伴一起，竭盡全力確保患者能夠在監管程序完成後獲得該產品。儘管如此，Clarity AD 強化了這項發現：去除大腦中的聚集形式 Abeta 可能與減緩認知能力下降有關。這非常重要，這也是我們透過 ADU 所展示的。目前，我們已有患者正在接受 EMBARK 研究的給藥治療。而 Priya 還會這麼說。

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。事實上——我沒有什麼好補充的。我想說的是，我們正在繼續研究 aducanumab，但尚未做出任何決定。目前，我們相信 EMBARK 資料集對科學界來說將非常有價值。這些患者已經接受 aducanumab 和抗澱粉樣蛋白治療多年。此外，鑑於 aducanumab 是第一個獲得加速批准的產品，我們還有一個上市後要求，這被稱為 ENVISION 研究。因此目前，ENVISION 和 EMBARK 都將繼續進行。

Your next question comes from Chris Raymond with Piper Sandler.

您的下一個問題來自 Piper Sandler 的 Chris Raymond。

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?

這也許只是與上一個問題相關的問題。那麼，由於 ADUHELM 的商業基礎設施已基本結束，我們應該如何考慮在 1 月份增加 lecanemab 基礎設施的支出？也許您可以談談從 ADUHELM 學到的經驗教訓，並向我們介紹一下在從潛在的加速批准轉向全面批准的過程中，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?

謝謝你的提問。我先開始，Mike 再補充。根據時間表以及 ADU NCD 決定與 lecanemab 讀數以及監管流程之間的差距，保持大量人員加入是不合理的。這本來是不合理的。所以我們別無選擇，只能採取這些行動。現在有一個新頁面。我們正在與合作夥伴一起進行評估，考慮各個公司在各大洲的實力和相對實力，因為我們打算大約同時在美國、歐洲和日本申請全面批准，以便在今年年初獲得加速批准。我們正在規劃投資，但尚未完全完成。因此，我們會以非常有節奏和可控的方式來進行這項工作，並從這裡開始。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。我想補充一點，隨著我們繼續與衛材討論商業化策略，利潤分成是 50-50。正如我們所說，他們擁有最終的決定權。顯然，我們都公開分享了從 ADUHELM 事件中學到的經驗教訓。我想說的是，我確實非常有信心——你會看到商業支出的成長與收入的接近程度將遠遠高於 ADUHELM，顯然，ADUHELM 上的許多事情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，我們能夠以某種方式衡量它——而且衛材也將能夠以某種方式衡量它，即支出的增長將比你在 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.

我要說──如果可以的話，我要說我們面臨一個新的進程。幾年前我們認為加速意味著產品發布，但事實並非如此。所以現在，我們有一個概述的新流程，然後我們將嚴格控制公司資源擴大規模的方式。

Your next question comes from Matthew Harrison with Morgan Stanley.

您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。我想回答另一個問題，我認為我們從投資者那裡得到了很多，即關於某些亞群或人群是否有潛力表現出色並推動 lecanemab 頂線結果的很大一部分。所以，您能否確認一下，如果情況確實如此，例如，如果某個特定子群體是導致該反應的主要驅動因素，您會在第一行就指出這一點嗎？或者我們在進入 CTAD 時應該如何思考這個問題？

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.

我可以回答這個問題。謝謝你的提問，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-Sum of Boxes，其 p 值為 0.00005。所以這非常非常重要。這是一場大型審判。因此，大約有 1,800 名參與者，其中包括代表性不足的人群。並且它滿足了所有次要終點，即認知和功能獨立的領域。

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.

因此總的來說，我們認為結果非常非常積極而且非常令人鼓舞。目前，衛材尚未分享亞組分析的細節，我認為我們需要等待 CTAD 才能看到有關主要終點和次要終點的更多細節。但在這一點上，我想說，總的來說，我們相信我們只需要等待，我們對所看到的營收感到非常鼓舞。我無法評論您可能看到或看不到的具體內容。我認為我們必須等待 CTAD。

Your next question comes from Brian Skorney with Baird.

您的下一個問題來自貝爾德 (Baird) 的布萊恩·斯科尼 (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?

我想知道您是否可以概述一下皮下注射 lecanemab 的大致時間表。只是想知道該途徑是什麼樣的，然後也許您正在尋求初始和慢性劑量的批准？或者這更像是最初的一個標籤，可以讓一段時間內開始靜脈注射的患者轉換使用？當我們思考這條路徑向前​​發展時，您認為您與 FDA 在 SABRE 亞臨床治療的互動中，有哪些經驗可以藉鏡？

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。而皮下製劑的開發已經在第三階段開放標籤擴展中進行。我們也 — Eisai 也正在與 FDA 合作。因此，有很多討論正在進行中。我只想說第一階段的生物利用度數據已經公開分享。所以我已經分享了這個。正如我在評論中提到的，他們目前正在研究每週 720 毫克的固定劑量，並正在進行評估。

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.

但該計劃的時間表和其他可能還需要什麼細節尚未公佈。所以我想說，我們只需等待它被分享，我們會在適當的時候分享它。但這是一項非常重要的努力並且正在持續進行。

Your next question comes from Michael Yee with Jefferies.

您的下一個問題來自 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 報銷和必須等待 CTAD 數據的評論，我想也許您可以談談有什麼途徑或什麼類型的互動（如果有的話），或者您可以採取什麼方法與 CMS 一起推動緊迫性，無論是患者倡導團體，無論你們是否正在努力做到這一點，或者他們是否只是看到與一年前 ADUHELM 的情況相比發生了明顯變化，他們會迅速採取行動。

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，衛材在吸引監管機構和付款人方面處於領先地位。據我們所知，衛材已開始與 CMS 合作。所以他們負責這項活動。目前我不會提供更多細節。但雙方的參與度是存在的，這是最重要的。

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

接下來我們來談談 Truist Securities 的 Robyn Karnauskas。

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.

我的問題有兩個面向。因此，我們經常聽到說禮來公司目前在該領域的影響力非常大，並且佔據了醫生的注意力。麥克，你提到，你傾向於——你認為我們會有更多——我試圖解讀你所說的話，即你將根據收入增加支出。能稍微詳細說明一下嗎？因為你在這個領域會有競爭對手。還有一個小問題想問 Priya。我們也聽說，您可能不想在已經存在 tau β 斑塊的患者身上進行 tau 病理學試驗，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。我只是想澄清我之前提出的觀點。當衛材與我們一起制定商業化策略時，顯然，首要目標就是正確發布產品，並建立支援最佳發布的基礎設施，然後我們就能夠做好準備。顯然，在 2021 年 6 月獲得 ADUHELM 批准時，我們已經建立了大型基礎設施並隨時投入使用。然後顯然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.

我想說的是，我們希望這不會是重演，並且我們將擁有適當的基礎設施來支援成功發射。這是首要任務。希望我們不會遇到這樣的延誤。因此，您會看到支出會在收入之前增加，但不會有像 ADUHELM 那樣的差距。

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.

我還可以補充一點，羅賓。謝謝，麥克。我可以補充一點。就醫生和心智份額而言，我認為，從科學角度來看，這顯然是一個發展非常迅速的領域，我認為 lecanemab 已經證明去除斑塊可以產生臨床影響。這確實非常重要。我還想補充一點，安全性在這裡非常非常重要。例如，對於 lecanemab，我們的 ARIA 發生率約為 21%。我們發現這符合預期。

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醫生來說都是值得重視的。因此總的來說，雖然我認為問題可能更多地與發布有關，但我想說的是，人們的心態將取決於數據。我認為，我們需要先了解其他抗澱粉樣蛋白療法的數據，然後才能決定什麼療法是有意義的。我認為的另一點是，我們將自己視為先驅者。我們得到了這些非常令人鼓舞的數據。我們認為這是一個非常廣泛和複雜的患者群體，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.

因此我們認為這是一個非常重要的地方，在這裡我們可以真正為患者帶來幫助。然後 Robyn，關於第二個問題，您能澄清一下嗎？我沒太聽懂。最後你們還是分手了。

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，抱歉。因此對於 tau 病理學，一些科學家認為在註射 tau 之前需要清除斑塊。換句話說，tau 可能無法單獨發揮作用。現在我們了解了生物學原理，您可能需要將它與 lecanemab 結合。對所有正在進行的這些試驗（包括 080）的想法，例如——您是否認為它們可能不起作用，因為您實際上需要使用像 lecanemab 這樣的 Abeta 藥物來清除斑塊？

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。所以我想我會退一步來說，顯然澱粉樣蛋白病理學非常關鍵。我們也相信它可能位於 tau 病理的上游。透過 aducanumab 的數據，我們確實顯示了它對磷酸化 tau 等的影響。因此，我們認為整體而言，這種級聯非常重要。

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，也許阿茲海默症的未來取決於幹預的時機，我已經談到了這一點，這是一個非常不同的問題。但也有可能一種方法並不夠充分。這裡的問題是，我們試圖以系統化和有條不紊的方式處理這個問題。因此，我們現在已經證明 lecanemab 確實可以去除聚集的斑塊，從而產生臨床影響。我認為衛材在今年早些時候也曾分享過這一結果，基於 IIb 期和建模的數據，這可以使患者在病情發展到更為嚴重的阿茲海默症階段之前保留大約 2 到 3 年的時間。這是基於第二階段的建模和數據。我知道他們已經公開表示他們也將對第三階段的數據進行此類分析。

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，我們正在單獨研究 BIIB080，我們在 Ib 期試驗中獲得了非常令人鼓舞的結果，結果顯示 tau 呈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 問題。現在我們正處於啟動第二階段的進程。但你完全正確。我們將研究多種不同的方法，以盡最大努力使患者受益。所以是的，所有生物學都需要考慮，但我們需要逐步進行，並且我們需要有系統地進行。

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.

如果我可以補充一下思想分享的話。流行病學規模如此之大。基礎設施方面有太多需要建設，因此我們都歡迎其他公司的努力。具體來說，關於 lecanemab，我知道你們已經與你們中的一些人進行了交流。我們已經與科學領袖和臨床醫生進行了接觸。從我們所聽到的來看，我認為反饋非常積極。最終，6 個月內的療效以及 18 個月研究期內的療效和安全性將成為這些化合物之間的差異。但在現階段，我們歡迎一切為有需要的患者準備市場的努力。

Your next question comes from Jay Olson with Oppenheimer.

您的下一個問題來自奧本海默公司的傑伊·奧爾森。

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?

恭喜您獲得 Clarity AD 成果。我很好奇您與 Denali 合作的可能性，以及您計劃如何利用他們的電視平台推廣 Abeta 抗體，包括 lecanemab 和 ADUHELM。既然我們有了明確的 DAD 結果，您是否認為更好的腦滲透性可以改善 Abeta 抗體的治療效果？那麼，從電視節目中提名候選人的時間表是怎樣的呢？

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。這是一個非常好的問題。我可以與你們分享的是，我們正在審視我們的投資組合，我們正在研究我們現有的幾個合作夥伴關係，以了解我們如何能夠真正地利用這些數據的力量以及我們所看到的生物學假設的力量。我無法對 Denali 電視平台發表更具體地評論。但是是的，一切都擺在桌面上。我們將仔細研究所有事情，並在其變得相關且適當時發佈公告。謝謝。

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

接下來我們去拜訪 Cowen and Company 公司的 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​​獲得的經驗的後續問題。 Biogen 最近對 lecanemab 的價格有何看法？您是否認為，由於數據更好，其價格會高於 ADUHELM，還是會因為阻力而打折？並且認識到 Eisai 對所有商業化決策擁有最終決定權，Biogen 將在製定 lecanemab 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.

正如您所預料的，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.

接下來我們訪問的是 SVB 證券公司的馬克古德曼 (Marc Goodman)。

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?

您能否向我們詳細介紹一下 OUS SPINRAZA，其動態如何？那裡有什麼關於價格上漲或積極的定價動態嗎？然後，Priya，您能否確認一下，每週的皮下注射劑量是 720 毫克，這是我們要使用的劑量嗎？還是我們還在研究給藥方案？

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，歐洲的發展勢頭正因 risdiplam 的推出而放緩。但我們正在分享患者轉換的數據，美國患者出於療效原因從 risdiplam 重新轉換回 SPINRAZA。所以我認為——我們正在向美國學習。我們正在向美國學習。我們相信這將成為其他大洲學習的典範。除歐洲核心地區外，我們看到銷售成長非常迅速，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。麥克，你想添加嗎？

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，馬克，根據你問題的精神，更多的是針對 OUS。我們提到美國表現平平。還有 OUS。整體來看，下降幅度不大。但是，如果以固定匯率計算剔除外匯，實際上是有所增長的，而且這種增長與我們在準備好的評論中提到的要點一致，銷量略有下降，這主要是由於德國、加拿大和日本等地的競爭，而且我們還有一些時間因素，比如俄羅斯、巴西和其他一些國家，但這被中國銷量的增長部分抵消了。

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.

但我們在歐洲一些市場的價格確實有所上漲，但漲幅超過了銷售量。因此，具體來說，交易量略有下降，但價格上漲略有抵消，而且外匯走勢與 OUS 背道而馳。

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.

我將很快總結第二點。我認為您—您的第二個問題，衛材已經表示，每週 720 毫克的固定劑量是相當於每兩週每公斤 10 毫克靜脈注射的劑量。事實上，它也已被列入最近宣布的自動注射器研究名單。我想這就是問題所在。如果您有不同的想法，請糾正我。謝謝。

We'll go next to Chris Schott with JPMorgan.

接下來我們參觀的是摩根大通的 Chris Schott。

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?

在我們等待皮下注射和維持計劃期間，您能否再稍微談談 lecanemab 兩週靜脈注射療法的動態？我想，除了報銷之外，您認為從商業和基礎設施的角度來看這將有多大挑戰？我知道您不是在談論時間，但您設想的這個相對較短的時間窗口是否將使用當前的劑量模式，或者是否可以在較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。因此我認為總體而言，我們看到了每公斤每兩週 10 毫克劑量的非常好的數據。我認為這裡非常非常相關的要點是在 6 個月時就出現了分離，早在 6 個月時，就沒有滴定，並且絕對範圍擴大，直到 Clarity AD 中 18 個月的主要終點讀數。所以這是非常令人鼓舞的數據。

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.

我想說，隨著阿茲海默症等相關疾病的治療基礎設施的建成，患者得到醫生的診治實際上變得非常重要。因此，如果這是問題的話，我們並不認為這一定是缺點。我們不認為這是缺點。但話雖如此，我們正在盡一切努力。衛材正在領導這項工作，我們正在努力確保將患者的便利性放在心上，這是皮下注射發展的前提。因此我無法評論靜脈注射需要多長時間以及何時轉為皮下注射。但我們在製定臨床開發計劃時，會從高層次和細節層面非常仔細地研究所有這些方面，並考慮到所有這些主題。

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.

因此總的來說，我們認為在早期階段，患者每兩週去診所就診一次其實非常重要。

Your next question comes from Paul Matteis with Stifel.

您的下一個問題來自 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，您如何描述 lecanemab 推出之前目前神經病學診所的輸液能力？今天它在哪裡？您認為需要進行多少提升才能隨著時間的推移實現更廣泛的訪問？

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，我們看到 ADUHELM 系統表現出一定的適應性，如果有報銷的話，它會將一些現有的輸液中心轉移到潛在的 ADUHELM。我們從未得到退款，所以這種事從未發生過。總的來說，我認為有必要擴大規模，提高產能。但從我們的學習中，我們可以看到該系統具有靈活性，並且可根據當前容量進行調整。

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

您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.

這只是 lecanemab 發布支出的後續報導。在你們今年早些時候進行重組之後，您能否談談可以重新部署的製造資產，或者您為 ADUHELM 進行的一些商業投資，這些投資可以重新分配給 lecanemab 的發布？我只是想要了解明年的支出規模與採用規模之間的關係。

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。所以，傑夫，我有幾點評論。謝謝你的提問。首先我想說的是，在製造方面，我們在北卡羅來納州羅利市擁有一個重要的工廠，然後在瑞士索洛圖恩擁有一個相對較新的工廠。位於瑞士索洛圖恩的工廠將主要用於生產阿茲海默症產品，目前該工廠主要致力於增加庫存，為 lecanemab 的上市做好準備。我認為截至本季末我們手頭上的庫存略高於 1 億美元。可以這麼說，該設施的效率與 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.

隨著 ADUHELM 變得更具市場價值，我們也可以利用該設施。這就是那裡的現狀。將會有一些閒置產能。本季的營收約為 1200 萬美元。隨著產品產量的增加，我們將不得不承擔一些閒置產能費用。我想說，在商業基礎設施方面，沒有太多東西能夠或將被從 ADUHELM 中重新利用。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 2022 年 4 月我們收到 NCD 到 lecanemab 完全商業化以維持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，我們承諾的 10 億美元成本節約計畫中，大部分成本已被消除。因此，在很大程度上，lecanemab 的商業化將是一個新的平台和新的基礎設施的建設。

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

今天早上的通話到此結束。感謝大家加入我們。

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。您現在可以斷開連線。