Biogen Inc (BIIB) 2022 Q2 法說會逐字稿

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

早上好。我叫凱蒂，今天我將成為您的會議接線員。在這個時候，我想歡迎大家參加百健（Biogen）第二季度財報電話會議和財務更新。 （操作員說明）

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

謝謝你。我現在想將電話轉給投資者關係主管 Mike Hencke 先生。 Hencke 先生，你可以開始你的會議了。

Good morning, and welcome to Biogen's Second 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 a reconciliation of the GAAP to non-GAAP financial measures that we will discuss today. Our GAAP financials are provided in Tables 1 and 2, and Table 4 includes a reconciliation of our GAAP to non-GAAP financial results.

早上好，歡迎來到百健（Biogen）公司 2022 年第二季度財報電話會議。在我們開始之前，我鼓勵大家去 biogen.com 的投資者部分查找收益發布和相關財務表格，包括我們的 GAAP 財務指標以及我們今天將討論的 GAAP 與非 GAAP 財務指標的對賬。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.

我們相信非公認會計準則財務業績更好地代表了我們業務的持續經濟狀況，並反映了我們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，以跟踪與此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。

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.

這些陳述受到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 SEC 的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)

在今天的電話會議上，我們的首席執行官 Michel Vounatsos 加入了我的行列； Priya Singhal 博士，研發臨時主管；和我們的首席財務官 Mike McDonnell。 （操作員說明）

I will now turn the call over to Michel.

我現在將把電話轉給米歇爾。

Good morning, everyone, and thank you for joining us. Biogen continued to execute well in the second quarter, and we are pleased to be raising our full year financial guidance. We believe our key achievements this quarter are critical steps on our path to drive renewed value creation for both patients and shareholders over time.

大家早上好，感謝您加入我們。百健（Biogen）在第二季度繼續表現良好，我們很高興提高全年財務指導。我們相信，我們本季度的主要成就是我們為患者和股東推動新價值創造的道路上的關鍵步驟。

First, together with Eisai, we are granted priority review for lecanemab under the accelerated approval pathway in the U.S. for early Alzheimer's disease. We expect an FDA decision by January 6 of next year. And in parallel, we look forward to the upcoming Phase III readout expected in the fall. Additionally, together with Sage, we reported positive data in postpartum depression.

首先，我們與衛材一起，在美國加速批准早期阿爾茨海默病的途徑下，我們獲得了 lecanemab 的優先審評。我們預計 FDA 將在明年 1 月 6 日之前做出決定。與此同時，我們期待著即將在秋季發布的第三階段讀數。此外，我們與 Sage 一起報告了產後抑鬱症的積極數據。

The SKYLARK study is now the second positive Phase III study supporting the potential of zuranolone in PPD with four additional positive randomized controlled trials in major depressive disorders. We believe there is a substantial body of evidence supporting a significant opportunity for zuranolone.

SKYLARK 研究現在是支持 zuranolone 在 PPD 中的潛力的第二項陽性 III 期研究，另外還有四項針對重度抑鬱症的陽性隨機對照試驗。我們相信有大量證據支持 zuranolone 的重大機遇。

Pursuit of innovation, however, does not come without setbacks, and we were disappointed to learn that the BIIB104 Phase II study in schizophrenia was not positive. I will now focus on the near-term operational priorities we outlined in our last call while Priya will review our recent progress in R&D, and Mike will discuss our second quarter performance.

然而，追求創新並非一帆風順，我們很失望地得知 BIIB104 II 期精神分裂症研究並不積極。我現在將專注於我們在上次電話會議中概述的近期運營優先事項，而 Priya 將審查我們最近在研發方面的進展，Mike 將討論我們第二季度的業績。

First, we are continuing to focus our R&D resources on programs where we see the greatest potential while also aiming to rebalance the risk profile across our pipeline. For example, we intend to accelerate the regulatory filing of zuranolone in postpartum depression following the positive SKYLARK study. In addition, we have terminated some R&D programs that we believe lower positive success such as BIIB076, an anti-tau antibody in Alzheimer's disease; and BIIB100, a small molecule XPO1 inhibitor in ALS.

首先，我們將繼續將我們的研發資源集中在我們認為潛力最大的項目上，同時還旨在重新平衡我們管道中的風險狀況。例如，我們打算在積極的 SKYLARK 研究之後加速 zuranolone 在產後抑鬱症中的監管備案。此外，我們已經終止了一些我們認為成功率較低的研發項目，例如用於治療阿爾茨海默病的抗 tau 抗體 BIIB076；和 BIIB100，一種用於 ALS 的小分子 XPO1 抑製劑。

Second, we are on track to implement the cost reduction and productivity measures outlined on our last call in order to further align our costs with our revenue base while maintaining our focus on execution. Third, we are pursuing additional global growth opportunities with a focus on key emerging markets. This includes China, where we are encouraged by the launch of SPINRAZA. Fourth, we are focused on driving renewed growth in our biosimilars business. We just recently launched BYOOVIZ, the first biosimilar referencing LUCENTIS in the U.S., representing Biogen's first entry into the U.S. biosimilars market. We also expect to begin launching BYOOVIZ outside the U.S. early next year.

其次，我們正在實施上次電話會議中概述的降低成本和提高生產力的措施，以進一步使我們的成本與我們的收入基礎保持一致，同時保持我們對執行的關注。第三，我們正在尋求更多的全球增長機會，重點關注主要新興市場。這包括中國，我們對 SPINRAZA 的推出感到鼓舞。第四，我們專注於推動生物仿製藥業務的新增長。我們最近剛剛推出了 BYOOVIZ，這是美國第一個參考 LUCENTIS 的生物仿製藥，代表 Biogen 首次進入美國生物仿製藥市場。我們還預計明年初開始在美國以外地區推出 BYOOVIZ。

With the completion of the sales of our joint venture interest in Samsung Bioepis in the second quarter, we now have an expanded ability to pursue the biosimilars business on our own, as we aim to bring more biosimilars products to more patients in more geographies. We continue to advance our biosimilars pipeline, which includes two Phase III programs referencing Eylea and ACTEMRA.

隨著我們在第二季度完成對三星 Bioepis 合資企業權益的銷售，我們現在擁有更大的自主從事生物仿製藥業務的能力，因為我們的目標是為更多地區的更多患者帶來更多的生物仿製藥產品。我們繼續推進我們的生物仿製藥管道，其中包括兩個參考 Eylea 和 ACTEMRA 的 III 期項目。

Fifth, we remain focused on capital allocation during the quarter. We entered into new collaborations with MedRhythms in MS and Alectos in Parkinson's disease, and we continue to evaluate both internal and excellent value creation opportunities. We also returned approximately $500 million to shareholders during the quarter through share repurchases. We are also pleased with the progress in our collaboration with Genentech for mosunetuzumab, a CD20/CD3 bispecific antibody which was recently approved in the EU for patients with relapsed or refractory follicular lymphoma.

第五，我們在本季度仍然專注於資本配置。我們與 MS 的 MedRhythms 和帕金森病的 Alectos 進行了新的合作，我們將繼續評估內部和卓越的價值創造機會。我們還在本季度通過股票回購向股東返還了大約 5 億美元。我們也很高興與基因泰克合作開發 mosunetuzumab，這是一種 CD20/CD3 雙特異性抗體，最近在歐盟獲批用於復發或難治性濾泡性淋巴瘤患者。

The BLA of mosunetuzumab for the same indication was recently granted priority review by the FDA, and we look forward to a potential approval in the U.S. Our progress across these areas in addition to the recent advancements we have made in R&D have the potential to help drive growth over time. Of course, we know that not all our programs will deliver the results we hope, which is why we are continuing to advance and build a diversified and appropriately balanced pipeline as we work to create and sustain a multi-franchise portfolio over time.

用於同一適應症的 mosunetuzumab 的 BLA 最近獲得了 FDA 的優先審查，我們期待在美國獲得潛在批准。除了我們在研發方面取得的最新進展外，我們在這些領域取得的進展有可能幫助推動隨著時間的推移而增長。當然，我們知道並非我們所有的計劃都能實現我們希望的結果，這就是為什麼我們在努力創建和維持多特許經營組合的過程中繼續推進和建立多元化和適當平衡的渠道。

This includes near-term opportunities in Alzheimer's disease and depression followed by other areas such as Parkinson's disease, lupus and stroke in the mid- to late 2020s. We remain committed to taking advantage of all the strengths of the company: our talent, our commercial portfolio, our manufacturing capabilities, our pipeline, which includes 10 programs in Phase III or filed and our strong balance sheet to deliver results for both the patients we serve and our shareholders.

這包括阿爾茨海默病和抑鬱症的近期機會，然後是 2020 年代中後期的帕金森病、狼瘡和中風等其他領域。我們仍然致力於利用公司的所有優勢：我們的人才、我們的商業組合、我們的製造能力、我們的管道，其中包括 10 個處於 III 期或已提交的項目，以及我們強大的資產負債表，為我們的患者提供結果服務和我們的股東。

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

我現在將把電話轉給 Priya，以了解我們最近在研發方面取得的進展。

Thank you, Michel, and good morning, everyone. I would like to start by thanking the Biogen team for their focus and dedication as we continued to advance a robust and diversified R&D pipeline. As Michel mentioned, we had several exciting R&D achievements this past quarter that I believe are key steps toward advancing our pursuit of meaningful new therapies for patients.

謝謝你，米歇爾，大家早上好。首先，我要感謝 Biogen 團隊在我們繼續推進強大和多元化的研發管道時的專注和奉獻。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，我相信這是推動我們為患者尋求有意義的新療法的關鍵步驟。

Starting with Alzheimer's disease. As Michel mentioned, the FDA has accepted and granted priority review for the BLA for lecanemab in early Alzheimer's disease under the accelerated approval pathway. Eisai is also continuing to progress the lecanemab Phase III Clarity study with an expected readout this fall. The Clarity AD study was designed to build upon the results of the prior Phase II study and utilizes clinically validated assessments designed to evaluate various aspects of cognition and function. Given the robust trial design, we believe that the totality of the Clarity AD results should allow us to further understand the effect of amyloid removal on different clinical domains of Alzheimer's disease.

從阿爾茨海默病開始。正如 Michel 所提到的，在加速批准途徑下，FDA 已接受並授予對 lecanemab 用於早期阿爾茨海默病的 BLA 的優先審查。衛材還在繼續推進 lecanemab III 期 Clarity 研究，預計將於今年秋季公佈。 Clarity AD 研究旨在建立在先前 II 期研究的結果的基礎上，並利用旨在評估認知和功能的各個方面的臨床驗證評估。鑑於穩健的試驗設計，我們認為 Clarity AD 結果的整體應該使我們能夠進一步了解澱粉樣蛋白去除對阿爾茨海默病不同臨床領域的影響。

The FDA has agreed that Clarity AD, when completed, can serve as a confirmatory study to verify the clinical benefit of lecanemab. Pending the results of the Clarity AD study, Eisai plans to file for traditional approval of lecanemab in the U.S., EU and Japan by the end of Q1 2023. This timing may allow for lecanemab, if approved, to become the first anti-amyloid antibody for Alzheimer's disease with traditional approval.

FDA 已同意 Clarity AD 完成後可作為驗證性研究來驗證 lecanemab 的臨床益處。在 Clarity AD 研究的結果出來之前，衛材計劃在 2023 年第一季度末之前在美國、歐盟和日本申請 lecanemab 的傳統批准。如果獲得批准，這個時間可能允許 lecanemab 成為第一個抗澱粉樣蛋白抗體傳統批准用於阿爾茨海默病。

Last quarter, using simulation modeling based on the lecanemab Phase II results, Eisai also published an analysis estimating the potential long-term health outcomes of treatment with lecanemab. The results of this analysis suggests that compared to standard of care alone, individuals treated with lecanemab in addition to standard of care may potentially experience slower disease progression to mild, moderate and severe Alzheimer's disease from baseline by 2.51, 3.13 and 2.34 years on average, respectively. These preliminary results could possibly translate into additional quality-adjusted life years and reduction in formal and informal cost of this disease. Beyond lecanemab, we continue to advance (inaudible) pipeline that is diversified across molecular targets and modalities. This includes BIIB080, our ASO targeting tau, where we expect to initiate a Phase II study later this year.

上個季度，衛材使用基於 lecanemab II 期結果的模擬建模，還發布了一項分析，估計了 lecanemab 治療的潛在長期健康結果。該分析的結果表明，與單獨的護理標準相比，除了標準護理外，接受萊卡尼單抗治療的個體可能會從基線平均延遲 2.51 年、3.13 年和 2.34 年疾病進展為輕度、中度和重度阿爾茨海默病，分別。這些初步結果可能會轉化為額外的質量調整生命年，並降低這種疾病的正式和非正式成本。除了 lecanemab，我們繼續推進（聽不清）跨分子靶點和模式多樣化的管道。這包括 BIIB080，我們針對 tau 的 ASO，我們預計將在今年晚些時候啟動 II 期研究。

Moving to neuropsychiatry. Together with Sage, we were very excited to announce positive results from the SKYLARK Phase III study of zuranolone in postpartum depression. The SKYLARK study met its primary endpoint and all key secondary endpoints with a 2-week course of 50 milligrams zuranolone, demonstrating a statistically significant improvement in depressive symptoms at day 15 as compared to placebo, the primary endpoint and at day 3, day 28 and 45. This is the second positive Phase III study of zuranolone in postpartum depression and further reinforces the clinical profile of zuranolone that has been observed to date.

轉向神經精神病學。我們與 Sage 一起非常高興地宣布 SKYLARK 三期研究 zuranolone 在產後抑鬱症中的積極結果。 SKYLARK 研究達到了其主要終點和所有關鍵次要終點，為期 2 週的 50 毫克 zuranolone 療程，與安慰劑、主要終點和第 3 天、第 28 天和45. 這是 zuranolone 在產後抑鬱症中的第二項陽性 III 期研究，進一步強化了迄今為止觀察到的 zuranolone 的臨床特徵。

Postpartum depression is one of the most common medical complications occurring during and after pregnancy, affecting an estimated 1 in 8 mothers or approximately 500,000 women in the United States each year. Depression, sadness, anxiety, thoughts of hurting oneself or one's infant and thoughts of suicide are common signs associated with PPD. This is an area of significant unmet need where new treatment options are desperately needed.

產後抑鬱症是在懷孕期間和之後發生的最常見的醫學並發症之一，在美國每年影響大約八分之一的母親或大約 500,000 名婦女。抑鬱、悲傷、焦慮、傷害自己或嬰兒的想法以及自殺想法是與 PPD 相關的常見跡象。這是一個嚴重需求未得到滿足的領域，迫切需要新的治療方案。

With the SKYLARK study results now in hand, we are working with Sage to advance a single regulatory filing for zuranolone in MDD and PPD in the U.S., which we expect to complete in the second half of this year. Last quarter, Sage also presented the results of the zuranolone human abuse liability potential study at the College on Problems of Drug Dependence Annual Meeting. The results of this study showed that 30 and 60 milligrams of zuranolone demonstrated lower abuse potential as compared with alprazolam 1.5 milligrams and 3 milligrams in recreational users of CNS depressants. 90 milligrams of zuranolone was comparable to alprazolam 1.5 milligrams and 3 milligrams. As a reminder, the zuranolone doses studied in the MDD and PPD trials were between 20 to 50 milligrams.

隨著 SKYLARK 研究結果的掌握，我們正在與 Sage 合作推進 zuranolone 在美國 MDD 和 PPD 的單一監管備案，我們預計將在今年下半年完成。上個季度，Sage 還在藥物依賴問題學院年會上展示了 zuranolone 人類濫用責任潛在研究的結果。這項研究的結果表明，與 1.5 毫克和 3 毫克的阿普唑侖相比，在中樞神經系統抑製劑的娛樂性使用者中，30 和 60 毫克的 zuranolone 顯示出較低的濫用潛力。 90 毫克的 zuranolone 與 1.5 毫克和 3 毫克的阿普唑侖相當。提醒一下，在 MDD 和 PPD 試驗中研究的 zuranolone 劑量在 20 到 50 毫克之間。

Also in neuropsychiatry, we were disappointed to learn that the TALLY Phase II study of BIIB104 in cognitive impairment associated with schizophrenia, or CIAS, did not meet its primary or secondary efficacy endpoints. Most adverse events in the BIIB104 treatment arms were mild to moderate in severity. Given the consistent lack of efficacy observed across the primary and secondary measures of cognition and functioning, while demonstrating expected drug exposure levels during the entire 12-week evaluation period, we have decided to discontinue the BIIB104 program in CIAS. We are continuing to analyze the data and plan to present detailed results at an upcoming scientific forum.

同樣在神經精神病學中，我們失望地得知 BIIB104 在與精神分裂症相關的認知障礙或 CIAS 中的 TALLY II 期研究沒有達到其主要或次要療效終點。 BIIB104治療組中的大多數不良事件的嚴重程度為輕度至中度。鑑於在認知和功能的主要和次要測量中觀察到的療效始終缺乏，同時在整個 12 週的評估期內展示了預期的藥物暴露水平，我們決定停止 CIAS 的 BIIB104 計劃。我們將繼續分析數據，併計劃在即將舉行的科學論壇上展示詳細結果。

Moving to our neuromuscular portfolio. Last month, we presented new 12-month data from the VALOR Phase III study and its open-label extension of tofersen in SOD1-ALS, a progressive and rare genetic form of ALS. This analysis was designed to evaluate participants who initiated tofersen during the 6-month placebo-controlled period in VALOR, versus individuals originally on placebo, who had a delayed start of tofersen treatment during the study's open-label extension. The results of the new 12-month analysis showed that initial -- earlier initiation of tofersen slowed decline across measures of clinical and respiratory function, strength and quality of life. Furthermore, tofersen led to robust and sustained reductions in neurofilament, a marker of axonal injury and neurodegeneration.

轉向我們的神經肌肉產品組合。上個月，我們展示了 VALOR III 期研究的 12 個月新數據及其在 SOD1-ALS（一種漸進和罕見的 ALS 遺傳形式）中 tofersen 的開放標籤擴展。該分析旨在評估在 VALOR 的 6 個月安慰劑對照期間開始使用 tofersen 的參與者，以及在研究的開放標籤擴展期間延遲開始使用 tofersen 治療的最初使用安慰劑的個體。新的 12 個月分析結果表明，最初 - 早期開始使用 tofersen 減緩了臨床和呼吸功能、力量和生活質量指標的下降。此外，tofersen 導致神經絲（軸突損傷和神經退行性變的標誌物）的持續減少。

We believe that these results build upon the encouraging trends [of reduced] disease progression originally observed in the VALOR 6-month randomized study and further support the potential for tofersen to slow disease progression in SOD1-ALS. We continue to engage global regulators with these data, and we will provide updates when appropriate.

我們相信，這些結果建立在最初在 VALOR 6 個月隨機研究中觀察到的令人鼓舞的 [減少] 疾病進展趨勢的基礎上，並進一步支持了 tofersen 減緩 SOD1-ALS 疾病進展的潛力。我們將繼續與全球監管機構合作處理這些數據，並將在適當時提供更新。

In movement disorders, we initiated the Phase IIb LUMA study in Parkinson's disease for BIIB122, a small molecule LRRK2 inhibitor that we are developing in collaboration with Denali Therapeutics. LRRK2 mutations result in hyperactivation of the kinase and are estimated to account for roughly 5% of familial and 2% of sporadic Parkinson's disease. By inhibiting LRRK2, BIIB122 is designed to target an underlying biological pathway implicated in Parkinson's disease, lysosomal function.

在運動障礙方面，我們啟動了針對 BIIB122 的帕金森病 IIb 期 LUMA 研究，BIIB122是我們與 Denali Therapeutics 合作開發的一種小分子 LRRK2 抑製劑。 LRRK2 突變導致激酶過度活化，估計約佔家族性帕金森病的 5% 和散發性帕金森病的 2%。通過抑制 LRRK2，BIIB122 旨在靶向與帕金森病有關的潛在生物學途徑，即溶酶體功能。

For this reason, we believe BIIB122 may have therapeutic potential in Parkinson's disease more broadly, both in people with and without pathogenic LRRK2 mutations.

出於這個原因，我們認為 BIIB122 可能在更廣泛的帕金森病中具有治療潛力，無論是在有和沒有致病性 LRRK2 突變的人中。

The LUMA study is designed to evaluate whether once-daily oral BIIB122 administration can slow clinical worsening versus placebo in Parkinson's disease patients without a pathogenic LRRK2 variant. We also anticipate initiating the Phase III LIGHTHOUSE study later this year designed to evaluate the safety and efficacy of BIIB122 in Parkinson's disease patients with a confirmed LRRK2 pathogenic variant.

LUMA 研究旨在評估在沒有致病性 LRRK2 變異的帕金森病患者中，與安慰劑相比，每日一次口服 BIIB122 是否可以減緩臨床惡化。我們還預計在今年晚些時候啟動 III 期 LIGHTHOUSE 研究，旨在評估 BIIB122在已確認 LRRK2致病性變異的帕金森病患者中的安全性和有效性。

There are roughly 10 million people suffering from Parkinson's disease worldwide and no approved treatments set slow disease progression. By inhibiting LRRK2, we have the potential to deliver a first-in-class therapy that may significantly alter the course of disease.

全世界大約有 1000 萬人患有帕金森病，並且沒有批准的治療方法可以減緩疾病的進展。通過抑制 LRRK2，我們有可能提供一流的治療方法，可以顯著改變疾病的進程。

In conclusion, we executed well against our R&D objectives in the second quarter and continue to prioritize our efforts across both therapeutic areas and programs. As Michel mentioned, we have already made several decisions resulting from this prioritization effort. And this is an ongoing process that will be driven by both scientific insights and internal inflection points.

總之，我們在第二季度的研發目標上執行得很好，並繼續優先考慮我們在治療領域和項目上的努力。正如 Michel 所提到的，我們已經做出了一些基於優先級排序的決定。這是一個持續的過程，將由科學見解和內部拐點驅動。

Looking toward the remainder of 2022, we anticipate several exciting milestones. These include the zuranolone regulatory filings for both MDD and PPD in the U.S., the Phase III readout of lecanemab in Alzheimer's disease and the initiation of mid- to late-stage studies in Alzheimer's, Parkinson's and lupus. These are therapeutic areas characterized by significant unmet need and where Biogen has an opportunity to deliver first-in-class and best-in-class therapies to patients.

展望 2022 年剩餘時間，我們預計會有幾個激動人心的里程碑。其中包括美國 MDD 和 PPD 的 zuranolone 監管文件，lecanemab 在阿爾茨海默病中的 III 期讀數以及阿爾茨海默病、帕金森病和狼瘡中晚期研究的啟動。這些治療領域的特點是需求未得到滿足，百健（Biogen）有機會為患者提供一流和一流的治療。

I will now pass the call over to Mike.

我現在將把電話轉給邁克。

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

謝謝你，普里亞，大家早上好。我將提供我們第二季度財務業績的一些亮點，並更新我們的 2022 年全年指導。請注意，除非另有說明，否則所有財務比較均與 2021 年第二季度進行比較。

Total revenue for the second quarter was $2.6 billion, which was a decrease of 7% at actual currency and 5% at constant currency. Non-GAAP diluted earnings per share in the second quarter was $5.25, a decrease of 6%. Total MS revenue inclusive of OCREVUS royalties was $1.7 billion, a decrease of 4% at actual currency and 3% at constant currency.

第二季度總收入為 26 億美元，按實際匯率計算下降 7%，按固定匯率計算下降 5%。第二季度非 GAAP 攤薄後每股收益為 5.25 美元，下降 6%。包括 OCREVUS 版稅在內的 MS 總收入為 17 億美元，按實際貨幣計算下降 4%，按固定貨幣計算下降 3%。

Global TECFIDERA revenue of $398 million decreased 18% at actual currency and 17% at constant currency. TECFIDERA revenue in the U.S. increased versus the prior quarter. However, this was primarily due to channel dynamics and we do expect TECFIDERA in the U.S. to decline throughout the remainder of 2022. Outside the U.S., TECFIDERA was modestly impacted by generic competition in markets such as Canada and Germany.

全球 TECFIDERA 收入為 3.98 億美元，按實際貨幣計算下降 18%，按固定貨幣計算下降 17%。 TECFIDERA 在美國的收入與上一季度相比有所增加。然而，這主要是由於渠道動態，我們預計美國的 TECFIDERA 將在 2022 年剩餘時間內下降。在美國以外，TECFIDERA 受到加拿大和德國等市場的仿製藥競爭的適度影響。

At this point, we are aware of several generic applications that have been approved in Europe, and we will be monitoring the situation closely. Importantly, we were pleased to be granted a new patent in the EU and reserve all rights to assert the patent against infringing generics, but it is possible that generics may still launch at risk.

目前，我們知道有幾個仿製藥申請已在歐洲獲得批准，我們將密切關注情況。重要的是，我們很高興在歐盟獲得一項新專利，並保留所有權利來主張該專利反對侵權仿製藥，但仿製藥仍有可能面臨風險。

Global VUMERITY revenue of $137 million increased 51% at actual currency and 52% at constant currency. VUMERITY continued to grow in the U.S. We are pleased with the trajectory. Outside the U.S., VUMERITY is now launched in 14 markets. We are currently working with our contract manufacturing suppliers to address potential supply constraints, and have therefore delayed any additional country launches.

全球 VUMERITY 收入為 1.37 億美元，按實際貨幣計算增長 51%，按固定貨幣計算增長 52%。 VUMERITY 在美國繼續增長。我們對這一發展軌跡感到滿意。在美國以外，VUMERITY 現已在 14 個市場推出。我們目前正在與我們的合同製造供應商合作，以解決潛在的供應限制，因此推遲了任何其他國家/地區的發布。

Global TYSABRI revenue of $516 million decreased 2% at actual currency and was flat at constant currency. In the United States, TYSABRI revenue was negatively impacted by modest volume declines, partially offset by favorable pricing. Outside the U.S., we were pleased to see continued patient growth. We are aware that regulatory filings for a biosimilar referencing TYSABRI have been submitted to both the FDA and the EMA. We will continue to enforce our IP, but a biosimilar could launch upon approval in the U.S. and EU, which could occur next year.

全球 TYSABRI 收入為 5.16 億美元，按實際貨幣計算下降 2%，按固定貨幣計算持平。在美國，TYSABRI 的收入受到銷量溫和下降的負面影響，部分被有利的定價所抵消。在美國以外，我們很高興看到患者持續增長。我們知道，引用 TYSABRI 的生物類似藥的監管文件已提交給 FDA 和 EMA。我們將繼續執行我們的知識產權，但生物仿製藥可能會在美國和歐盟獲得批准後推出，這可能會在明年發生。

Global Interferon revenue of $350 million decreased 13% at actual currency and 11% at constant currency and was impacted by the continued shift from the injectable platforms to oral or high-efficacy therapies. Versus the prior quarter, Interferon revenue increased 13% at actual currency and 14% at constant currency, primarily due to seasonality and channel dynamics in the U.S.

全球干擾素收入為 3.5 億美元，按實際匯率計算下降 13%，按固定匯率計算下降 11%，並受到從注射平台持續向口服或高效療法轉變的影響。與上一季度相比，干擾素收入按實際匯率計算增長 13%，按固定匯率計算增長 14%，主要是由於美國的季節性和渠道動態。

Moving to SMA. Global SPINRAZA revenue of $431 million declined 14% at actual currency and 11% at constant currency. In the U.S., we were encouraged to see fewer SPINRAZA discontinuations during the quarter. Outside the U.S., the revenue decline was primarily driven by competition, along with the timing of shipments in certain markets, pricing dynamics and negative currency impacts.

轉移到 SMA。全球 SPINRAZA 收入為 4.31 億美元，按實際貨幣計算下降 14%，按固定貨幣計算下降 11%。在美國，我們很高興看到本季度停止使用 SPINRAZA 的人數減少。在美國以外，收入下降的主要原因是競爭、某些市場的發貨時間、定價動態和負面貨幣影響。

Global SPINRAZA revenue decreased 9% versus the first quarter of 2022 at actual currency and 8% at constant currency, driven by competition and negative currency impacts outside the U.S. as well as some seasonality dynamics in the U.S.

由於美國以外的競爭和負面貨幣影響以及美國的一些季節性動態，全球 SPINRAZA 收入按實際貨幣計算與 2022 年第一季度相比下降了 9%，按固定匯率計算下降了 8%。

Moving to our biosimilars business. Revenue of $194 million declined 4% at actual currency and increased 3% at constant currency. Biosimilars volume increases were more than offset by negative currency impacts and pricing pressure. We continued to expect full year biosimilars revenue to decrease versus 2021.

轉向我們的生物仿製藥業務。收入為 1.94 億美元，按實際匯率計算下降 4%，按固定匯率計算增長 3%。生物仿製藥銷量的增長被負面的貨幣影響和定價壓力所抵消。我們繼續預計全年生物仿製藥收入將比 2021 年下降。

We are pleased to have launched BYOOVIZ this quarter in the U.S., and we recorded some modest initial revenue due to channel stocking. As a reminder, we expect a gradual launch of BYOOVIZ, with more meaningful revenue contribution starting in 2023. Total anti-CD20 revenue of $436 million decreased 1%. Revenue from OCREVUS royalties increased 14%, which was more than offset by continued RITUXAN declines due to biosimilar competition.

我們很高興本季度在美國推出了 BYOOVIZ，由於渠道庫存，我們錄得一些適度的初始收入。提醒一下，我們預計 BYOOVIZ 將逐步推出，從 2023 年開始有更有意義的收入貢獻。反 CD20 總收入為 4.36 億美元，下降 1%。來自 OCREVUS 特許權使用費的收入增長了 14%，這被生物仿製藥競爭導致的 RITUXAN 持續下降所抵消。

Now moving on to expenses and the balance sheet. Second quarter non-GAAP R&D expense was $529 million, including $18 million in upfront payments related to collaborations with MedRhythms and Alectos Therapeutics. This is compared to $585 million in the second quarter of 2021, which included approximately $50 million in upfront payments. Non-GAAP SG&A was $570 million, including approximately $29 million related to ADUHELM. This is compared to $635 million in the second quarter of 2021. Second quarter collaboration profit sharing was a net expense of $29 million, which includes $58 million of net profit sharing expense related to the collaboration with Samsung Bioepis, partially offset by reimbursement of $29 million from Eisai related to the commercialization of ADUHELM in the U.S. Non-GAAP other expense was $79 million, primarily driven by interest expense. GAAP other income was $429 million, which included two items of note.

現在轉到費用和資產負債表。第二季度非 GAAP 研發費用為 5.29 億美元，其中包括與 MedRhythms 和 Alectos Therapeutics 合作相關的 1800 萬美元預付款。相比之下，2021 年第二季度為 5.85 億美元，其中包括約 5000 萬美元的預付款。 Non-GAAP SG&A 為 5.7 億美元，包括與 ADUHELM 相關的約 2900 萬美元。相比之下，2021 年第二季度為 6.35 億美元。第二季度的合作利潤分成淨支出為 2900 萬美元，其中包括與三星 Bioepis 合作相關的 5800 萬美元的淨利潤分成費用，部分被 2900 萬美元的報銷所抵消衛材與 ADUHELM 在美國的商業化相關的非 GAAP 其他費用為 7900 萬美元，主要由利息費用驅動。 GAAP 其他收入為 4.29 億美元，其中包括兩個值得注意的項目。

First, we recorded an approximately $1.5 billion gain on the sale of our equity stake in the Samsung Bioepis joint venture. In addition, we recorded $900 million plus estimated fees and expenses related to an agreement in principle to resolve previously disclosed qui tam litigation relating to conduct prior to 2015. This agreement in principle does not include any admission of liability and is subject to the negotiation of final settlement agreements and documents. We expect to make the payment shortly after the agreements are finalized, which we expect to be as soon as possible and within the next 12 months.

首先，我們通過出售我們在三星 Bioepis 合資企業的股權獲得了大約 15 億美元的收益。此外，我們記錄了 9 億美元以及與一項原則上解決先前披露的與 2015 年之前的行為有關的 qui tam 訴訟的協議相關的估計費用和支出。該協議原則上不包括任何責任承認，並受制於最終和解協議和文件。我們預計在協議敲定後不久付款，我們預計將在未來 12 個月內盡快付款。

In the second quarter, we generated $737 million in cash flow from operations. Capital expenditures were $37 million and free cash flow was $700 million. We repurchased 2.4 million shares of the company's common stock during the quarter for $500 million. As of June 30, we ended the quarter with $7.3 billion in debt, $5.9 billion in cash and marketable securities and $1.4 billion in net debt. In July, we repaid our senior notes due September 2022, with an aggregate principal amount of $1 billion. Of note, as of June 30, we have capitalized approximately $71 million of work-in-process inventory related to lecanemab. We plan to continue building inventory over the coming months and we are also procuring raw materials associated with this production.

在第二季度，我們從運營中產生了 7.37 億美元的現金流。資本支出為 3700 萬美元，自由現金流為 7 億美元。我們在本季度以 5 億美元回購了 240 萬股公司普通股。截至 6 月 30 日，我們以 73 億美元的債務、59 億美元的現金和有價證券以及 14 億美元的淨債務結束了本季度。 7 月，我們償還了 2022 年 9 月到期的優先票據，本金總額為 10 億美元。值得注意的是，截至 6 月 30 日，我們已將大約 7100 萬美元的與 lecanemab 相關的在製品庫存資本化。我們計劃在未來幾個月內繼續建立庫存，並且我們還在採購與此生產相關的原材料。

If the lecanemab Phase III study is negative or if lecanemab does not receive regulatory approval, we would expect to expense inventory on hand at that time as research and development expense subject to cost sharing with Eisai. 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.

如果 lecanemab III 期研究是否定的，或者如果 lecanemab 沒有獲得監管部門的批准，我們預計當時手頭的庫存費用作為研發費用，需要與衛材分攤成本。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，其中包括 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。

Let me now turn to our updated full year 2022 guidance. We are increasing our full year revenue guidance from our previous range of $9.7 billion to $10 billion to a new range of $9.9 billion to $10.1 billion and increasing our full year non-GAAP diluted EPS guidance from our previous range of $14.25 to $16 to a new range of $15.25 to $16.75. This guidance increase is primarily a result of better-than-expected top line performance and continued cost management. This guidance assumes that foreign exchange rates as of July 15 will remain in effect for the remainder of the year, net of hedging activities.

現在讓我談談我們更新的 2022 年全年指南。我們將全年收入指引從之前的 97 億美元至 100 億美元提高到新的 99 億美元至 101 億美元，並將全年非公認會計準則攤薄後每股收益指引從之前的 14.25 美元至 16 美元提高到新的範圍範圍為 15.25 美元至 16.75 美元。這一指導增加主要是由於好於預期的頂線業績和持續的成本管理。該指引假設截至 7 月 15 日的匯率在扣除對沖活動後將在今年剩餘時間內保持有效。

Importantly, we are raising our revenue and EPS guidance ranges despite some meaningful currency headwinds, which were not included in our guidance at the beginning of the year. Specifically, subsequent to issuing our most recent guidance on May 3, we have experienced a headwind of approximately $55 million to revenue and $0.20 to EPS due to currency fluctuations from April 29 through July 15. This is in addition to a headwind of approximately $120 million to revenue and $0.35 to EPS due to currency fluctuations between January 1 and April 29. These currency headwinds are primarily due to strengthening of the U.S. dollar relative to other currencies in which we transact.

重要的是，儘管存在一些有意義的貨幣逆風，但我們正在提高我們的收入和每股收益指導範圍，而這些逆風並未包括在我們年初的指導中。具體來說，在 5 月 3 日發布我們最近的指導之後，由於 4 月 29 日至 7 月 15 日的貨幣波動，我們的收入和每股收益都受到了約 5500 萬美元的逆風和 0.20 美元的逆風。這是除了約 1.2 億美元的逆風之外由於 1 月 1 日至 4 月 29 日期間的貨幣波動，收入和每股收益 0.35 美元。這些貨幣逆風主要是由於美元相對於我們交易的其他貨幣走強。

This financial guidance assumes continued declines in RITUXAN revenue due to biosimilar competition as well as continued erosion of TECFIDERA revenue in the U.S. due to generic entry. Further, this guidance reflects a range of scenarios for the impact of TECFIDERA generics in the EU, which is difficult to predict. We are aware of a small number of generics that have launched to date, and we are monitoring the situation. We assume we will utilize a portion of the remaining share repurchase authorization of $2.3 billion throughout the remainder of the year. Please see our press release for other important guidance assumptions.

本財務指導假設 RITUXAN 收入由於生物仿製藥競爭而持續下降，以及由於仿製藥進入美國 TECFIDERA 收入持續下降。此外，該指南反映了 TECFIDERA 仿製藥在歐盟的影響的一系列情景，這是難以預測的。我們知道迄今為止已經推出了少數仿製藥，我們正在監控情況。我們假設我們將在今年剩餘時間內利用剩餘的 23 億美元股票回購授權的一部分。請參閱我們的新聞稿了解其他重要的指導假設。

In summary, we continued to execute well across our core business and are pleased to be raising our financial guidance for the year. We remain focused on delivering results and are optimistic about the potential opportunities ahead of us that we believe can create long-term value for shareholders. We will now open the call for questions.

總而言之，我們繼續在我們的核心業務中表現良好，並很高興提高我們今年的財務指導。我們仍然專注於取得成果，並對我們面前的潛在機會持樂觀態度，我們相信這些機會可以為股東創造長期價值。我們現在將打開問題的電話。

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

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

Congratulations on the nice quarter. So we noticed that -- and you discussed this a bit that you have been discontinuing pipeline programs maybe a little bit earlier on, including 104, 100 and 076. Just wondering if you could maybe comment on that, whether this reflects any change in your philosophy on risk assumption and go/no-go decision with respect to pipeline prioritization. And maybe how -- if that might imply anything for your bar to pursue approval of lecanemab if the Phase III study misses on its primary endpoint.

祝賀這個美好的季度。所以我們注意到 - 你討論了一點，你可能早些時候停止了管道項目，包括 104、100 和 076。只是想知道你是否可以對此發表評論，這是否反映了你的任何變化關於管道優先級的風險承擔和通過/不通過決策的理念。如果 III 期研究錯過了主要終點，這可能意味著你的酒吧尋求 lecanemab 的批准。

Priya will give some color.

Priya會給一些顏色。

Thank you, Brian, for that question. So as we've mentioned last quarter, we've embarked upon a very focused and disciplined prioritization of the R&D portfolio. But it is dependent on internal inflection points as well as external scientific insights. So I want to specifically pick up on the points that you made about BIIB104. We just shared that we will be discontinuing development of BIIB104, which is an AMPA potentiator in CIAS, which is cognitive impairment with -- associated with schizophrenia. And that is because we had a readout from TALLY where we saw expected pharmacological exposure, but we did not meet the primary or secondary endpoints. So we believe that we have tested the hypothesis really well here and that it's time to reconsider the data, look at it very carefully, think about other applications, but ensure that we allocate resources to the programs with higher probability of success. So that addresses that question.

謝謝你，布賴恩，這個問題。因此，正如我們上個季度所提到的，我們已經開始對研發組合進行非常專注和嚴格的優先排序。但這取決於內部拐點以及外部科學見解。所以我想具體談談你對 BIIB104 的看法。我們剛剛分享了我們將停止開發 BIIB104，它是 CIAS 中的一種 AMPA 增強劑，它是與精神分裂症相關的認知障礙。那是因為我們從 TALLY 讀取了預期的藥理暴露，但我們沒有達到主要或次要終點。所以我們相信我們已經很好地測試了這個假設，現在是時候重新考慮數據了，非常仔細地查看數據，考慮其他應用程序，但要確保我們將資源分配給成功概率更高的程序。所以這就解決了這個問題。

With BIIB076 that you also mentioned, it's an anti-tau antibody with our partnership with Neurimmune. And we did announce that we are closing down development at Biogen for it. So I would ask that you direct further questions of next steps on BIIB076 to Neurimmune. But from our perspective, we are focusing, for example, on BIIB080, which is our antisense oligonucleotide that affects all post-translational forms of tau. And we will be starting a Phase II late-stage, mid-stage trial later this year. So that's how we're thinking about our prioritization.

您還提到了 BIIB076，它是一種抗 tau 抗體，我們與 Neurimmune 合作。我們確實宣布我們正在關閉 Biogen 的開發。因此，我想請您將有關 BIIB076 的後續步驟的進一步問題直接提交給 Neurimmune。但從我們的角度來看，我們正在關注例如 BIIB080，這是我們的反義寡核苷酸，影響所有翻譯後形式的 tau。我們將在今年晚些時候開始第二階段的後期、中期試驗。這就是我們考慮優先級的方式。

And finally, to address what it does for our bar on Alzheimer's, I'll just say that we look forward to the results of Clarity AD for lecanemab. It is a well-powered, well-designed trial. It has, we believe, the right primary endpoint in CDR-Sum of Boxes. And we think that a statistically significant difference versus placebo would be clinically meaningful because of the instrument that's being utilized as a primary endpoint and also all the secondary endpoints.

最後，為了解決它對我們的阿爾茨海默病酒吧的作用，我只想說我們期待 Clarity AD 對 lecanemab 的結果。這是一項功能強大、設計精良的試驗。我們相信，它在 CDR-Sum of Boxes 中具有正確的主要終點。我們認為，與安慰劑相比，統計學上的顯著差異將具有臨床意義，因為該儀器被用作主要終點以及所有次要終點。

And in addition, we have a whole comprehensive program around lecanemab, which addresses presymptomatic patients as well as we're looking at maintenance along with Eisai and Phase II open-label extension and subcutaneous. So I think we will just wait for the data. As we have said, we expect to complete the filing, along with Clarity AD, should it be positive by Q1 2023. So I hope that answers the question.

此外，我們圍繞 lecanemab 制定了一個完整的綜合計劃，該計劃針對出現症狀前的患者，我們正在研究維護以及衛材和 II 期開放標籤擴展和皮下。所以我認為我們將等待數據。正如我們所說，如果到 2023 年第一季度呈陽性，我們希望與 Clarity AD 一起完成備案。所以我希望能回答這個問題。

And if I may add, we are delighted to be progressing with the filing of zuranolone and leca and waiting more data also for adu. For the earlier pipeline, we have expanded materially our pipeline. It's natural that, first of all, there is inherent risk with neuroscience, and it's natural that we always try to increase probability of success and select based on trigger point and science inside. And this is what Priya is doing.

如果我可以補充一下，我們很高興在提交 zuranolone 和 leca 方面取得進展，並等待 adu 的更多數據。對於早期的管道，我們已經大大擴展了我們的管道。很自然，首先，神經科學存在固有的風險，我們總是試圖增加成功的概率，並根據觸發點和內部的科學進行選擇，這是很自然的。這就是 Priya 正在做的事情。

We'll take our next question from Matthew Harrison with Morgan Stanley.

我們將向摩根士丹利的馬修哈里森提出下一個問題。

Great. I just wanted to follow up on lecanemab. So I guess the key question that I've been getting a lot is, in the discussions with the FDA around using a single confirmatory study here, do you have explicit feedback from the regulators on the p-value necessary here? Or is that going to be a review issue?

偉大的。我只是想跟進 lecanemab。所以我想我得到很多的關鍵問題是，在與 FDA 討論在這裡使用單一的確認性研究時，你是否有監管機構對這裡必要的 p 值的明確反饋？或者這將是一個審查問題？

Priya?

普里亞？

Thank you, Matthew. So just to step back, lecanemab has completed -- is in the filing for accelerated approval pathway using the Phase II study, which is the 201 study, and we are expecting results for Clarity AD, which is the Phase III study. This is a study with 1,795 subjects. It's a global study. We believe it's well powered. There is no interim or futility analysis. It will be just a primary readout sometime in the fall of this year, 2022. And currently, this has an underrepresented population also quite similar to the CMS population of about 25% included.

謝謝你，馬修。因此，退一步說，lecanemab 已經完成——正在申請使用 II 期研究的加速批准途徑，這是 201 研究，我們期待 Clarity AD 的結果，這是 III 期研究。這是一項涉及 1,795 名受試者的研究。這是一項全球研究。我們相信它的動力很好。沒有臨時或無效分析。這將只是 2022 年秋季某個時候的主要讀數。目前，這部分人口的代表性不足也與 CMS 人口非常相似，包括約 25%。

Now with regards to whether it can be a confirmatory study for traditional approval, yes. We do believe we have this agreement that should it read out positive, it can be the confirmatory study. So I do believe that, that is exactly what we believe. In addition, I'll just remind us that in the aducanumab briefing document, the FDA had stated that they would accept a statistically significant change on an inherently meaningful instrument such as the CDR-Sum of Boxes as evidence of a clinically meaningful effect.

現在關於它是否可以作為傳統批准的驗證性研究，是的。我們確實相信我們有這樣的協議，如果它的結果是積極的，它可以是驗證性研究。所以我確實相信，這正是我們所相信的。此外，我只想提醒我們，在 aducanumab 簡報文件中，FDA 曾表示，他們將接受對固有意義的工具（如 CDR-Sum of Boxes）進行統計學上顯著的變化，作為臨床意義效應的證據。

So this is really important. And we feel quite confident that CDR-Sum of Boxes is the right primary endpoint. It is clinically validated, and it combines both cognition and function and is widely accepted as a registrational endpoint. So we are at that point. We feel quite good about the fact that it's well powered. Of course, we have to wait to see the results. I hope that answers the question.

所以這真的很重要。我們非常有信心 CDR-Sum of Boxes 是正確的主要終點。它經過臨床驗證，結合了認知和功能，被廣泛接受為註冊終點。所以我們就在那個時候。我們對它功能強大的事實感到非常滿意。當然，我們還得等著看結果。我希望這能回答這個問題。

We'll take our next question from Colin Bristow with UBS.

我們將向瑞銀的 Colin Bristow 提出我們的下一個問題。

Congrats on the quarter. So just on the CEO search, could you give us an update on where you are in this process? And if you're able to now provide a time line. And just within that question, given how important lecanemab is to the company and the trajectory, is it reasonable to expect that a new CEO would not be in place until after the outcome of the trial is known?

祝賀本季度。因此，就 CEO 搜索而言，您能否向我們介紹一下您在此過程中的最新情況？如果您現在能夠提供時間線。就在這個問題中，鑑於 lecanemab 對公司和發展軌蹟的重要性，是否有理由期望在試驗結果公佈之前不會有新的 CEO 上任？

Thanks for the question. From my discussion earlier this week with the Board members and our Chairman, I hear that the search is progressing as planned. But at this stage, there is nothing yet to be reported. And obviously, we'll not speculate on lecanemab, but it's a very important event. But at this stage, nothing more to report.

謝謝你的問題。從我本週早些時候與董事會成員和我們的主席的討論中，我聽說搜索正在按計劃進行。但在現階段，還沒有任何報導。顯然，我們不會推測 lecanemab，但這是一個非常重要的事件。但在這個階段，沒有更多的報告。

We'll take our next question from Michael Yee with Jefferies.

我們將向 Jefferies 的 Michael Yee 提出下一個問題。

I had a question around -- thoughts around investment into SG&A and how that works for lecanemab, and whether there is a decision point as to your commitment to have to reimburse 50-50 and how that works if the drug actually gets to market. And then secondly, as that relates to zuranolone, same thing. Is that a proposed net investment spend for 2023? How do we think about that?

我有一個問題——關於對 SG&A 的投資的想法以及它對 lecanemab 的作用，以及是否有一個決定點來決定你必須償還 50-50 的費用，以及如果藥物真正進入市場，這將如何發揮作用。其次，與 zuranolone 有關，同樣的事情。這是 2023 年擬議的淨投資支出嗎？我們怎麼看？

Yes. So both of those arrangements are 50-50. So you would expect that we certainly will be building infrastructure to support, hopefully, the successful launch of both of those products, and we share costs in both cases, 50-50. So we're very focused on managing our OpEx. Currently, the 2022 guidance implies a midpoint of about $4.6 billion versus $5.2 billion last year, progressing well on the cost measures that we've committed to. And then, of course, the commercial infrastructure around those two products are key items that we're working very closely with both Sage and Eisai on, particularly as it relates to planning for 2023 and beyond.

是的。所以這兩種安排都是50-50。所以你會期望我們肯定會建立基礎設施來支持這兩種產品的成功推出，我們在這兩種情況下分攤成本，50-50。所以我們非常專注於管理我們的運營支出。目前，2022 年的指導意味著中點約為 46 億美元，而去年為 52 億美元，在我們承諾的成本措施方面進展順利。然後，當然，圍繞這兩種產品的商業基礎設施是我們與 Sage 和 Eisai 密切合作的關鍵項目，特別是與 2023 年及以後的規劃有關。

We'll take our next question from Umer Raffat with Evercore.

我們將向 Evercore 的 Umer Raffat 提出我們的下一個問題。

How do you intend to approach the lecanemab Phase III data set if the primary endpoint does not work but a secondary like ADCOMS or ADAS-Cog or perhaps a subgroup like APOE4 carriers is active? And how would that impact your FDA submission?

如果主要終點不起作用但 ADCOMS 或 ADAS-Cog 等次要終點或 APOE4 載體等亞組處於活動狀態，您打算如何處理 lecanemab III 期數據集？這將如何影響您的 FDA 提交？

Thank you, Umer. So maybe I can step back to say that we -- obviously, there are several scenarios of the data readout. And I think at one end, we have potentially a positive primary endpoint outcome with secondary endpoints as well. And we believe that the totality of the data will be really important. And as I said already, we do have -- we have discussed this, and we have agreement with the FDA that a positive readout could serve for a confirmatory study.

謝謝你，烏默爾。所以也許我可以退後一步說我們——顯然，數據讀出有幾種情況。而且我認為一方面，我們可能有一個積極的主要終點結果和次要終點。我們相信數據的整體性將非常重要。正如我已經說過的那樣，我們確實 - 我們已經討論過這個問題，並且我們與 FDA 達成了一致，即積極的讀數可以用於驗證性研究。

And on the other end of the spectrum, it's possible that the study is negative. And in that scenario, we would be looking at also the other readouts because there are two -- these are, obviously, Biogen-Eisai readout, but I will also draw attention to the fact that we have two other anti-amyloid agents reading out in the near term. One is gantenerumab and the other is donanemab, as everyone knows. So really, this is a bigger question about these readouts and what they mean for the anti-amyloid hypothesis in Alzheimer's -- early Alzheimer's disease.

另一方面，這項研究可能是負面的。在那種情況下，我們還會查看其他讀數，因為有兩個——顯然，這些是 Biogen-Eisai 讀數，但我也會提請注意我們還有另外兩種抗澱粉樣蛋白藥物讀數在短期內。一種是gantenerumab，另一種是donanemab，眾所周知。所以說真的，這是關於這些讀數的一個更大的問題，以及它們對阿爾茨海默病（早期阿爾茨海默病）中的抗澱粉樣蛋白假說意味著什麼。

There could be several mixed scenarios, some like you mentioned, and I think it will be very difficult to speculate exactly how that might be perceived. So I would say that the mix scenario, there could be several permutation combinations, but I think that the totality of the data is going to be important.

可能有幾種混合場景，就像你提到的那樣，我認為很難準確推測出這種情況會如何被感知。所以我會說混合場景，可能有幾個排列組合，但我認為數據的整體性很重要。

So at this point, it would be tough for me to speculate on what mix scenario and what outcome it could lead to. But we are considering all of this. And I think currently, our focus is on ensuring that we collect the data, close the study, have a very clear readout and then we will be engaging, of course, with the FDA. Because this product also has breakthrough and Fast Track designation, which allows us to consult the FDA for the guidance. So we will be in close contact, and that's what I can tell you. Thank you.

所以在這一點上，我很難推測什麼混合場景以及它可能導致什麼結果。但我們正在考慮所有這些。我認為目前，我們的重點是確保我們收集數據，結束研究，有一個非常清晰的讀數，然後我們當然會與 FDA 合作。因為該產品還具有突破性和快速通道指定，這使我們可以諮詢 FDA 以獲得指導。所以我們將保持密切聯繫，這就是我可以告訴你的。謝謝你。

We'll take our next question from Marc Goodman with SVB Securities.

我們將向 SVB 證券的 Marc Goodman 提出下一個問題。

You keep referring to the growth opportunity in emerging markets. Can you just help us size how big is the business? How has it been growing? What are the key products that are growing there? What are some products that have yet to launch there that's in the pipeline that can we look forward to growth there? Just give us a sense of where this business is going to be in 3, 4 years.

您一直提到新興市場的增長機會。你能幫我們確定一下業務的規模嗎？它是如何成長的？那裡正在增長的主要產品是什麼？有哪些尚未推出的產品正在籌備中，我們可以期待在那裡的增長？讓我們了解一下這項業務在 3、4 年後的發展方向。

So before Mike gives -- provides more color, the important element is that the epidemiology is pretty similar in this, in the West, in emerging mature markets. So our portfolio is very relevant to this part of the world. The second point is that we see a very strongly emerging middle class that is able to afford, able to co-pay and is willing to access best education and health care. And the experience we have so far with our expanded footprint since a few years in Latin America, in Asia Pac, in the Middle East, is that we see a very good uptake of our MS portfolio even if we thought at the outset that in Asia Pac, it was a bit lower incident. But based on the number of the population, these are very feasible opportunities.

因此，在邁克給出更多色彩之前，重要的一點是，在西方，在新興成熟市場，流行病學非常相似。因此，我們的產品組合與世界的這一地區非常相關。第二點是，我們看到一個非常強大的新興中產階級，他們有能力、有能力共同支付並願意獲得最好的教育和醫療保健。迄今為止，我們在拉丁美洲、亞太地區和中東的擴張足蹟的經驗是，我們看到我們的 MS 產品組合得到了很好的吸收，即使我們一開始就認為在亞洲Pac，這是一個較低的事件。但從人口數量來看，這些都是非常可行的機會。

We see a very good uptake and also for SPINRAZA. So a good opportunity. We have a professional team. Compliance is very important everywhere, but also in this part of the world. So we secure that we have a very good balance between where Biogen is directly and where Biogen is partnered, but we have a very good performance to date with a strong double-digit momentum. Mike?

我們看到了很好的吸收，也看到了 SPINRAZA。所以是個好機會。我們有專業的團隊。合規在任何地方都非常重要，在世界的這個地區也是如此。因此，我們確保我們在 Biogen 的直接位置和 Biogen 的合作夥伴之間取得了很好的平衡，但迄今為止我們的表現非常好，勢頭強勁，兩位數的勢頭強勁。麥克風？

Yes, not a lot to add, Marc. I would say that we're pleased with a couple of markets that I would call out, one being China, the other being Brazil. In particular, China, we're seeing excellent uptake on SPINRAZA. It's not a huge revenue contributor due to pricing dynamics there. But I think overall, the majority of our international growth has been around SMA. But as Michel said, there's opportunity in MS as well. And that's something that's gone from a very small revenue base to a respectable number as we sit here in 2022 and growing in the years beyond. So we're hopeful that we can continue to grow it meaningfully for the next several years.

是的，沒有太多要補充的，馬克。我想說我們對我會提到的幾個市場感到滿意，一個是中國，另一個是巴西。特別是在中國，我們看到了 SPINRAZA 的良好吸收。由於那裡的定價動態，它不是一個巨大的收入貢獻者。但我認為總體而言，我們的大部分國際增長都圍繞著 SMA。但正如 Michel 所說，MS 也有機會。當我們在 2022 年坐在這裡並在以後的幾年裡不斷增長時，這已經從一個非常小的收入基礎變成了一個可觀的數字。所以我們希望在接下來的幾年裡我們可以繼續有意義地發展它。

We'll take our next question from Salveen Richter with Goldman Sachs.

我們將從高盛的 Salveen Richter 那裡得到下一個問題。

Could you provide us any updates on how you're thinking about pricing and branding of zuranolone and thoughts here on how a potential Schedule IV could impact utilization?

您能否向我們提供有關您如何考慮 zuranolone 的定價和品牌以及關於潛在附表 IV 如何影響利用率的想法的任何更新？

So first, we are very encouraged by the data. I'm delighted to see the second study in postpartum for study in major depressive disorders. We had opportunities to meet many constituency. And this disease is affecting so many people, so it's so relevant. If I'm not mistaken, in the U.S., more than 19 million (sic) [10 million] as Priya said, an incident for PPD close to 0.5 million every year. So extremely relevant. We are making a lot of progress on the positioning on understanding the patient journey and the different segments of the market between the naive and the failure to treatment the way we know in this massive market due to side effects or lack of efficacy. I hope that in the near future, we'll be -- we'll have an opportunity together with Sage to have a dedicated session with you to update you on where we stand, and we'll come back to that as soon as we can. Concerning the price, we are not yet there. We are making some our homework, but nothing to add yet at this stage.

首先，我們對數據感到非常鼓舞。我很高興在產後看到第二項研究主要抑鬱症的研究。我們有機會會見許多支持者。這種疾病影響了很多人，所以它是如此相關。如果我沒記錯的話，在美國，正如 Priya 所說，超過 1900 萬（原文如此）[1000 萬]，PPD 每年發生的事件接近 50 萬。所以非常相關。我們在了解患者旅程的定位方面取得了很大進展，以及由於副作用或缺乏療效而在這個龐大的市場中我們所知道的幼稚和未能治療之間的不同市場細分。我希望在不久的將來，我們將 - 我們將有機會與 Sage 一起與您進行一次專門的會議，向您介紹我們的最新情況，我們會盡快回到那個能夠。關於價格，我們還沒有。我們正在做一些功課，但在這個階段還沒有什麼要補充的。

I can address the scheduling question. Thank you, Salveen. So I just wanted to say that if you step back, the DEA process is quite robust, and they will -- this typically takes about 3 months at the end of the approval process, and they will designate a schedule. Now Sage has already completed their human abuse liability potential study, as I mentioned in my opening comments. And there could potentially be 5 schedules that you could get. At present, what we do know is the data that we have, and we also have the background of ZULRESSO, which is a Schedule IV drug. So at this point, we do believe that it is possible for zuranolone to get a Schedule IV. And Schedule IV is typically -- what it means is low potential for abuse and low risk for dependence.

我可以解決調度問題。謝謝你，薩爾文。所以我只想說，如果您退後一步，DEA 流程將非常穩健，他們會-- 這通常需要在批准流程結束時大約 3 個月，他們會指定一個時間表。正如我在開篇評論中提到的那樣，現在 Sage 已經完成了他們的人類虐待責任潛在研究。您可能會獲得 5 個時間表。目前，我們所知道的是我們擁有的數據，我們也有 ZULRESSO 的背景，它是一種附表 IV 藥物。因此，在這一點上，我們確實相信 zuranolone 有可能獲得附表 IV。附表 IV 通常是——這意味著低濫用的可能性和低的依賴風險。

The other drugs in this category are Ativan, Xanax, Darvocet and others. And we believe that this is currently the expected scheduling. Of course, we have to wait to go through the process to see what the outcome will be, but that's what we expect at the moment with the data we have. I hope that addresses it. Thank you.

此類別中的其他藥物是 Ativan、Xanax、Darvocet 等。我們認為這是目前預期的調度。當然，我們必須等待通過這個過程才能看到結果是什麼，但這正是我們目前所擁有的數據所期望的。我希望能解決它。謝謝你。

We'll take our next from Robyn Karnauskas with Truist Securities.

我們將與 Truist Securities 一起從 Robyn Karnauskas 那裡獲得我們的下一個。

Sorry, I'm losing my voice. So I know you've talked a lot about staying within the current pillars of neurology and maybe also immunology. I was just wondering, if you think about derisking the portfolio and maybe going outside those pillars, what are your current thoughts about that now given you've had 3 months to think about it? And then I guess the question that goes along with that is, would you make that decision after you hire the final Head of R&D and CEO?

對不起，我失去了聲音。所以我知道你已經談了很多關於保持在當前神經學甚至免疫學的支柱。我只是想知道，如果您考慮降低投資組合的風險並可能走出這些支柱，鑑於您已經有 3 個月的時間考慮，您目前對此有何想法？然後我想隨之而來的問題是，您會在聘請最終的研發主管兼首席執行官後做出決定嗎？

I can get started. Thank you for the question. So just stepping back, we have -- at Biogen, we've got a vision towards a multi-franchise portfolio. And R&D, our pipeline, I believe, is quite strong and diversified and robust. We have 29 programs in the clinic, many more in our discovery and exploratory portfolio, where we look at the diseases that we want to be leaders in and we think about the targets and biological pathways that we may want to address with our platform actually of multiple modalities. So that's the other strength we have. We could be agnostic to modality because we have access to biologics, small molecules, antisense oligonucleotides as well as gene therapy. So that's sort of at a high level. That's how we think about our R&D portfolio.

我可以開始了。感謝你的提問。所以退一步說，我們有——在百健，我們有一個多特許經營組合的願景。我相信，我們的研發線非常強大、多元化和穩健。我們在臨床上有 29 個項目，還有更多在我們的發現和探索組合中，我們著眼於我們希望成為領導者的疾病，並考慮我們可能希望通過我們的平台實際解決的目標和生物學途徑多種方式。這就是我們擁有的另一個優勢。我們可能對模態不可知論，因為我們可以獲得生物製劑、小分子、反義寡核苷酸以及基因療法。所以這有點高水平。這就是我們對研發組合的看法。

Now within that, you spoke about neuroscience. This is an absolute core strength that we have. It's a very hard space, I would acknowledge. I think we would all acknowledge it. But we've had a lot of success in this space, both with multiple sclerosis as well as with spinal muscular atrophy. And potentially, we could have success with Alzheimer's. And certainly, we have zuranolone in depression. So we are thinking about this as neuroscience, potentially increasing our focus in neuropsychiatry where we've got now a product that is in filing for both MDD and PPD with a large high unmet need, and we are looking at other potential indications for the GABAA pathway that zuranolone addresses. So zuranolone could really be much more than just MDD and PPD, and we're looking at that as well in our portfolio prioritization.

現在，你談到了神經科學。這是我們擁有的絕對核心力量。這是一個非常艱難的空間，我承認。我想我們都會承認這一點。但是我們在這個領域取得了很多成功，包括多發性硬化症和脊髓性肌萎縮症。並且潛在地，我們可以在阿爾茨海默氏症方面取得成功。當然，我們有抑鬱症患者的 zuranolone。因此，我們將其視為神經科學，可能會增加我們對神經精神病學的關注，我們現在已經獲得了一種產品，該產品正在申請 MDD 和 PPD 且具有很大的未滿足需求，我們正在尋找 GABAA 的其他潛在適應症zuranolone 解決的途徑。所以 zuranolone 可能真的不僅僅是 MDD 和 PPD，我們也在考慮我們的投資組合優先級。

Shifting over to specialized immunology. We have three Phase III trials, and this is really important with two products. So we have our homegrown BIIB059, which where we understand the biology and the pathway really well. We think it could be first-in-class, best-in-class for CLE, cutaneous lupus erythematosus, but also for SLE. And then we have dapi with our collaboration with UCB, also in Phase III. So this is a comprehensive sort of portfolio just in SLE and CLE. There, again, we are thinking about where else do we understand the type 1 interferon signature, where else could we have potential indications with BIIB059, for example, in other specialized immunology indications? That's our core focus currently.

轉向專門的免疫學。我們進行了三個 III 期試驗，這對於兩種產品來說非常重要。所以我們有我們本土的 BIIB059，我們非常了解生物學和途徑。我們認為它可能是 CLE、皮膚紅斑狼瘡和 SLE 的一流、一流的。然後我們與 UCB 合作，在第三階段也有 dapi。因此，這是 SLE 和 CLE 中的綜合性投資組合。再一次，我們正在考慮我們在哪裡了解 1 型乾擾素特徵，我們還能在哪裡獲得 BIIB059 的潛在適應症，例如，在其他專門的免疫學適應症中？這是我們目前的核心重點。

And then finally, I'll say that within neuroscience, we think we can be leaders in Alzheimer's, depression and retain our leadership in MS and SPINRAZA. SMA, we have already discussed externally our opt in for BIIB115, which is a follow-on ASO with potentially a once-a-year dosing. So that could really be very, very important. We are accelerating that as much as we can. And we have MS, where we continue to think of BTK inhibitors. So we have a peripheral BTK inhibitor. We also have a central BTK inhibitor, and we will continue to look at the emerging data and make decisions.

最後，我要說的是，在神經科學領域，我們認為我們可以成為阿爾茨海默氏症、抑鬱症的領導者，並保持我們在 MS 和 SPINRAZA 方面的領導地位。 SMA，我們已經在外部討論了我們對 BIIB115 的選擇，這是一個後續的 ASO，可能每年一次給藥。所以這真的非常非常重要。我們正在盡可能地加速這一進程。我們有 MS，我們繼續考慮 BTK 抑製劑。所以我們有一個外周BTK抑製劑。我們還有一個中央 BTK 抑製劑，我們將繼續關注新出現的數據並做出決策。

Beyond this core R&D portfolio, as Michel mentioned, we also have our biosimilars and our digital therapeutics. We've just made a foray with MedRhythms. And I think that this -- to get altogether is a very diversified portfolio. The area that we've increased a lot of focus is as soon as we have, for example, we had the BIIB104 readout. We're now thinking of what else we would do with that glutamatergic pathway and the data that we will gather from there. Similarly, with BIIB059 and zuranolone, as I mentioned, how would we allocate resources to that? What would we prioritize? So we are doing this in a very systematic fashion, and it's a call-out to the R&D and the entire One Biogen team to really be doing this very well. I hope that gives you a flavor of how we are approaching it.

正如 Michel 所提到的，除了這個核心研發組合之外，我們還擁有我們的生物仿製藥和數字療法。我們剛剛嘗試了 MedRhythms。我認為這 - 完全是一個非常多元化的投資組合。我們已經增加了很多關注的領域，例如，我們有 BIIB104 讀數。我們現在正在考慮如何處理谷氨酸能通路以及我們將從那裡收集的數據。同樣，正如我提到的，對於 BIIB059 和 zuranolone，我們將如何分配資源？我們會優先考慮什麼？所以我們正在以一種非常系統的方式來做這件事，這是對研發和整個 One Biogen 團隊的呼籲，要真正做好這件事。我希望這能讓您了解我們是如何處理它的。

Thank you, Priya. And to bring that together, what is very important for us to set the strategic direction is to clearly understand the key capabilities that we have within the company throughout the value chain, from the early research, clinical development throughout to commercialization and customer engagement. And as Priya said, today, we believe that we are pretty well diversified compared where we were 6 years ago in neuroscience, in specialized immuno, in biosimilars and emerging digital therapeutics capability. We have now 29 programs, 10 in Phase III of filed products. The question is how do we derisk in addition? And this is what Priya started to work on.

謝謝你，普里亞。將這些結合在一起，對我們設定戰略方向非常重要的是清楚地了解我們在整個價值鏈中公司擁有的關鍵能力，從早期研究、臨床開發到商業化和客戶參與。正如 Priya 所說，今天，我們相信與 6 年前相比，我們在神經科學、專業免疫、生物仿製藥和新興的數字治療能力方面已經相當多元化。我們現在有29個項目，其中10個處於三期備案產品中。問題是我們如何除風險？這就是 Priya 開始著手的工作。

Obviously, a new CEO and a permanent Head of R&D, will have an opportunity to revisit the strategy together with the Board.

顯然，新任 CEO 和常任研發主管將有機會與董事會一起重新審視該戰略。

We'll take our next question from Cory Kasimov with JPMorgan.

我們將向摩根大通的 Cory Kasimov 提出下一個問題。

Going back to Alzheimer's for a minute. So in the face of the recent NCD and with the CLARITY study obviously pending, how do you think about the relative importance of the January PDUFA for lecanemab for accelerated approval that's based primarily on Phase II data? And has the FDA given any indication if they convene an ADCOM for this initial application?

回到阿爾茨海默氏症一分鐘。因此，面對最近的 NCD 和 CLARITY 研究顯然懸而未決，您如何看待主要基於 II 期數據的 lecanemab 加速批准的 1 月份 PDUFA 的相對重要性？如果他們為這個初始申請召集 ADCOM，FDA 是否給出了任何指示？

Priya?

普里亞？

Thank you, Cory. So first -- firstly, I think that just to step back, we have filed according to the accelerated approval pathway with the Phase II data, as you mentioned, Cory, and the PDUFA date for that is January 6, 2023. Now Clarity AD will readout in the fall of this year. And should it be positive, it will be -- the filing for traditional approval will be completed by what Eisai has communicated, by the end of the first quarter of 2023. In addition, I think that the totality of the information and the data will matter for the outcome. At the moment, we have -- we do not have an indication that there will be an advisory committee. At this moment, we do not have that indication. So that's what I can tell you on -- about that. I hope I addressed all the aspects of your question.

謝謝你，科里。所以首先——首先，我認為只是退後一步，我們已經根據加速批准途徑提交了第二階段數據，正如你提到的，Cory，PDUFA 日期是 2023 年 1 月 6 日。現在 Clarity AD將於今年秋季公佈。如果它是積極的，它將是 - 傳統批准的申請將由衛材傳達的信息，到 2023 年第一季度末完成。此外，我認為信息和數據的整體將事關結果。目前，我們有——我們沒有跡象表明會有一個諮詢委員會。目前，我們沒有那個跡象。所以這就是我可以告訴你的——關於那個。我希望我解決了你問題的所有方面。

We'll take our next question from Jay Olson with Oppenheimer.

我們將向奧本海默的傑伊奧爾森提出我們的下一個問題。

Can you talk about why BIIB104 did not meet the primary or secondary endpoints in the Phase II TALLY trial? And would you consider BIIB104 for a study in other indications?

您能談談為什麼 BIIB104 在 II 期 TALLY 試驗中沒有達到主要或次要終點嗎？您會考慮將 BIIB104 用於其他適應症的研究嗎？

Thank you, Jay. Great question. So yes, we are very disappointed with the negative readout for BIIB104. And just to step back, the hypothesis that we were testing was that AMPA potentiation can impact NMDA hypofunction -- NMDA receptor hypofunction and thereby, increase synaptic connectivity and increase the working memory domain -- impact the working memory domain positively in cognitive impairment that's associated with schizophrenia. So that was the hypothesis. And we were looking forward to the results. Of course, it has not met primary or secondary endpoints.

謝謝你，傑。好問題。所以是的，我們對 BIIB104 的負讀數非常失望。退一步說，我們正在測試的假設是 AMPA 增強會影響 NMDA 功能減退 - NMDA 受體功能減退，從而增加突觸連接並增加工作記憶域 - 在相關的認知障礙中對工作記憶域產生積極影響患有精神分裂症。這就是假設。我們期待著結果。當然，它還沒有達到主要或次要終點。

Now in neuropsychiatry trials, sometimes you don't have the right adherence and compliance during the trial. So we have looked very carefully at the PK exposures and such. And this was a 12-week readout. So we have looked at that, and we have quite -- we feel quite confident that this was a very high -- highly compliant trial where we have expected exposures for BIIB104 throughout the 12-week duration. So we believe that we have tested the hypothesis of AMPA potentiation leading to NMDA potentiation as well.

現在在神經精神病學試驗中，有時您在試驗期間沒有正確的依從性和依從性。因此，我們非常仔細地查看了 PK 曝光等。這是一個為期 12 週的讀數。所以我們已經研究過了，我們非常 - 我們非常有信心這是一個非常高 - 高度合規的試驗，我們預計 BIIB104 在 12 週的持續時間內會暴露。因此，我們相信我們已經檢驗了 AMPA 增強導致 NMDA 增強的假設。

Having said that, we think that this was an extremely well-run trial, and we have collected a very rich data set that can give us leads on how we might want to pursue the glutamatergic pathway in other neuropsychiatry indications. So yes, that is something that we are looking at very carefully, and we will be evaluating this very carefully. We did have early Phase I trials, but that data was unfortunately not replicated. Now these are very small trials. One was in healthy volunteers and the other one was in schizophrenia patients, but they were shorter duration and the subject numbers were 39 and 29, respectively. So very small trials. So yes, to your question, neuropsychiatry remains an area of high focus. We believe we've increased our capabilities and focus in this area, and we'll continue to look at this very high-quality data set, and we'll also be presenting it at upcoming medical meetings.

話雖如此，我們認為這是一個運行得非常好的試驗，我們收集了一個非常豐富的數據集，可以為我們提供有關我們可能希望如何在其他神經精神病學適應症中尋求谷氨酸能途徑的線索。所以是的，這是我們正在非常仔細地研究的東西，我們將非常仔細地評估它。我們確實進行了早期的 I 期試驗，但不幸的是，這些數據沒有被複製。現在這些都是非常小的試驗。一名是健康志願者，另一名是精神分裂症患者，但他們的持續時間較短，受試者人數分別為 39 和 29。所以非常小的試驗。所以是的，對於你的問題，神經精神病學仍然是一個高度關注的領域。我們相信我們已經提高了我們在這一領域的能力和重點，我們將繼續研究這個非常高質量的數據集，我們還將在即將舉行的醫學會議上展示它。

We'll take our next question from Phil Nadeau with Cowen.

我們將與 Cowen 一起回答 Phil Nadeau 的下一個問題。

A follow up to Cory's question but directed specifically at Mike. Mike, how does Biogen feel about putting resources behind the lecanemab launch? What would be the timing of an infrastructure build and the true launch of the product? Would it be after accelerated approval, after full approval? Or it does seem like now there's another step within NCD likely to come at some point. So when would Biogen feel comfortable in really investing in the commercial infrastructure for this program?

對 Cory 問題的跟進，但專門針對 Mike。邁克，百健（Biogen）對將資源用於 lecanemab 的推出有何感想？基礎設施建設和產品真正推出的時間是什麼時候？是在加速批准之後，還是在完全批准之後？或者，現在似乎在 NCD 中可能會在某個時候邁出另一步。那麼，Biogen 什麼時候才能真正為這個項目投資商業基礎設施呢？

So before Mike jumps in, I would like to say that we work in full and close collaboration with our partners at Eisai, that we are approaching a global launch, not suddenly a U.S. launch, and we anticipate the filing in Japan and EMA to take place during the first half of 2023. So this will be a global launch. And obviously, as we know, there is a sequential process here between an accelerated approval and a potentially full approval after that. Mike?

因此，在邁克加入之前，我想說的是，我們與衛材的合作夥伴進行了全面而密切的合作，我們正在接近全球發布，而不是突然在美國發布，我們預計在日本和 EMA 的申請將採取地點在 2023 年上半年。所以這將是全球發布。顯然，正如我們所知，在加速批准和之後可能的完全批准之間有一個連續的過程。麥克風？

Yes. I think Michel covered a lot of it in terms of the question, Phil, but I would just say that as a reminder, that we and Eisai expect the Phase III readout for lecanemab in the fall of 2022. The PDUFA date is in early January of '23. As you know, as currently written, the national coverage determination does significantly limit the market opportunity for antibodies with accelerated approval. And so as Michel said, we will closely align with Eisai to resource appropriately. We'll take learnings from ADUHELM as necessary and as where we can, and we'll resource it at each phase of its commercialization very gradually as lecanemab is launched. I'd say that, obviously, we did make the decision to take down the ADUHELM commercial infrastructure because we felt the time gap was too large to the timing of when we would need it for lecanemab. And I think that, that was the right decision. We feel like we can rebuild the infrastructure in a more gradual fashion and fairly quickly when we're ready. And again, that's something that we'll partner very closely with Eisai on.

是的。我認為 Michel 就這個問題涵蓋了很多，Phil，但我只想提醒一下，我們和衛材預計 2022 年秋季 Lecanemab 的 III 期讀數。PDUFA 日期是 1 月初'23.如您所知，正如目前所寫的那樣，國家覆蓋範圍的確定確實大大限制了加速批准抗體的市場機會。正如 Michel 所說，我們將與衛材密切合作，以適當地提供資源。我們將在必要時和盡可能從 ADUHELM 那裡學習，並且隨著 lecanemab 的推出，我們將在其商業化的每個階段非常逐步地為其提供資源。我想說的是，很明顯，我們確實做出了拆除 ADUHELM 商業基礎設施的決定，因為我們覺得時間差距太大，以至於我們需要它用於 lecanemab 的時間。我認為，這是正確的決定。我們覺得我們可以在準備好後以更漸進的方式和相當快的速度重建基礎設施。再說一次，我們將在這方面與衛材密切合作。

I think that it will very much be dependent on the quality of the data. If the data clarifies and confirms without any ambiguity, that removing the plaque is correlated with the slowing down of a cognitive decline and reinforces the hypothesis, I think [arrows with a line] faster than what we believe.

我認為這在很大程度上取決於數據的質量。如果數據澄清並毫不含糊地證實，去除斑塊與認知衰退的減緩相關並強化了假設，我認為[帶線的箭頭]比我們相信的要快。

Yes. And the other thing to remember here, this is purely from an accounting standpoint, and it ties back a little bit to the question that Mike Yee asked earlier. Just as a reminder, all of the revenue costs, everything will be aggregated and our 50% share will be reflected as a one-line revenue item for lecanemab.

是的。這裡要記住的另一件事，這純粹是從會計的角度來看，它與 Mike Yee 之前提出的問題有點聯繫。提醒一下，所有的收入成本，一切都將被匯總，我們 50% 的份額將反映為 lecanemab 的單行收入項目。

We'll take our next question from Geoff Meacham with Bank of America.

我們將向美國銀行的 Geoff Meacham 提出下一個問題。

Just want to follow up on some previous questions on lecanemab. You guys have talked about the U.S. opportunity already, but how much of a discussion have you had with EU or Japanese regulators just on the risk/benefit bar? I wasn't sure if your prior discussions from adu were able to give you some insight there.

只是想跟進有關 lecanemab 的一些先前問題。你們已經談論過美國的機會，但你們與歐盟或日本監管機構就風險/收益標准進行了多少討論？我不確定您之前與 adu 的討論是否能夠讓您對此有所了解。

Thank you, Geoff. So Eisai has communicated that they will be completing the filing in both Europe as well as in Japan by the end of Q1 2023, very similar to the U.S. time line. This is, of course, post Clarity AD readout should be positive. And in line with that communication, all the communications with regulators around the world, they are in line -- they have been in consultation. In Japan, Eisai actually has communicated and we have communicated previously that they have been part of its prior consultation process.

謝謝你，傑夫。因此，衛材表示，他們將在 2023 年第一季度末之前在歐洲和日本完成申請，這與美國的時間線非常相似。當然，這是後 Clarity AD 讀數應該是積極的。根據這種溝通，與世界各地監管機構的所有溝通，他們都是一致的——他們一直在協商。在日本，衛材實際上已經進行了溝通，我們之前也曾溝通過，他們一直是其事先諮詢過程的一部分。

Now the prior consultation process in Japan has the ability to really expedite the review process, should the data be positive. So that's also taking place. So all the -- everything is on track to complete the submission. Benefit/risk will always drive the discussions, and we believe that the trial is set up, well powered and well designed to give us an answer on a clinically validated instrument. So we believe that it is set up well. We, of course -- the rest will depend on the data.

現在日本的事前諮詢程序有能力真正加快審查過程，如果數據是積極的。所以這也在發生。所以所有-- 一切都在按計劃完成提交。收益/風險將始終推動討論，我們相信該試驗已建立、動力良好且設計良好，可以在臨床驗證的儀器上為我們提供答案。所以我們相信它設置得很好。當然，我們——其餘的將取決於數據。

We'll take our next question from Evan Seigerman with Bank of Montreal.

我們將向蒙特利爾銀行的 Evan Seigerman 提出下一個問題。

Just looking ahead to the Clarity AD trial, what do you think CMS needs to see from that trial to potentially revise the NCD? I know there's a lot of discussion on the call. But I'm wondering, is that sufficient to essentially open up access in the Medicare population.

展望 Clarity AD 試驗，您認為 CMS 需要從該試驗中看到什麼以可能修改 NCD？我知道電話會議上有很多討論。但我想知道，這是否足以從根本上開放醫療保險人群的使用權。

Thank you, Evan. So I think that before we kind of -- before I answer that directly, it would be important for us to kind of reiterate that the final NCD indicated that antibodies with full approval may be covered in CMS-approved prospective comparative studies and -- but that this data could be collected in a registry. Now what is left open to interpretation here is their next point that they made, which is that the degree of rigor in these study designs may depend in good part on the strength of evidence of the initial randomized controlled trial that led to FDA approval. This aspect, we feel quite good about because we think that the trial is well designed and well set up and well powered to give us a readout. So we believe that if the trial reads out positive, that is the Clarity AD, that there would be a chance that it would meet the high level of evidence bar that NCD has put forward from -- that CMS has put forward in the NCD and that they could potentially reconsider for full coverage.

謝謝你，埃文。所以我認為，在我們有點——在我直接回答之前，我們必須重申，最終的非傳染性疾病表明完全批准的抗體可能包含在 CMS 批准的前瞻性比較研究中，並且——但是可以在註冊表中收集此數據。現在有待解釋的是他們提出的下一個觀點，即這些研究設計的嚴謹程度可能在很大程度上取決於導致 FDA 批准的初始隨機對照試驗的證據強度。在這方面，我們感覺很好，因為我們認為試驗設計得很好，設置得很好，動力很好，可以給我們一個讀數。因此，我們認為，如果試驗結果為陽性，即 Clarity AD，那麼它就有可能達到 NCD 提出的高水平證據標準——CMS 在 NCD 中提出的他們可能會重新考慮全面覆蓋。

The other aspect to consider here is that there are two other readouts coming in the same sort of time frame, which could also influence how CMS looks at their guidance and what they designate as a high level of evidence. So it's not clear to us at this point, but it will depend on each molecule. Phase III data is my personal interpretation on this. Now as Eisai has announced, Clarity has a robust design, and they believe that it could meet the high level of evidence set forth by CMS in the NCD memo. So we do think that it could be reconsidered. And I think the high level of evidence would have to include safety, efficacy underrepresented population that mirrors the CMS population. In addition, I would say that the population in the Clarity AD also has comorbidities and concomitant medications not very dissimilar from the CMS population. So I think these things set us up well and they bode well. I think final outcome will depend on the data.

這裡要考慮的另一個方面是，在同一時間範圍內還有另外兩個讀數，這也可能影響 CMS 如何看待他們的指導以及他們指定的高水平證據。所以目前我們還不清楚，但這取決於每個分子。 III期數據是我個人對此的解讀。現在，正如衛材宣布的那樣，Clarity 具有強大的設計，他們相信它可以滿足 CMS 在 NCD 備忘錄中提出的高水平證據。所以我們確實認為可以重新考慮。而且我認為高水平的證據必須包括反映 CMS 人群的安全性、有效性代表性不足的人群。此外，我想說 Clarity AD 中的人群也有合併症和伴隨的藥物，與 CMS 人群並沒有太大的不同。所以我認為這些事情讓我們很好，而且預示著很好。我認為最終結果將取決於數據。

And to add to what Priya said, beyond the solid design, there is an open-label extension that will add some information. There is also a preclinical trial ongoing for the earlier population and life cycle management opportunities with new subcutaneous formulation also on the way.

為了補充 Priya 所說的內容，除了實體設計之外，還有一個開放標籤擴展，可以添加一些信息。還有一項針對早期人群和生命週期管理機會的臨床前試驗正在進行中，新的皮下製劑也在進行中。

And that will conclude our call today. Thank you, everyone, for joining us.

這將結束我們今天的電話會議。謝謝大家加入我們。

That will conclude today's call. We appreciate your participation. You may now disconnect.

這將結束今天的電話會議。我們感謝您的參與。您現在可以斷開連接。