施貴寶 (BMY) 2020 Q3 法說會逐字稿

Good day, and welcome to the Bristol-Myers Squibb 2020 Third Quarter Results Conference Call. Today's conference is being recorded. At this time, I would like to turn the conference over to Mr. Tim Power, Vice President, Investor Relations. Please go ahead, sir.

美好的一天，歡迎參加百時美施貴寶 2020 年第三季度業績電話會議。今天的會議正在錄製中。現在，我想將會議交給投資者關係副總裁 Tim Power 先生。請繼續，先生。

Thanks, Kevin, and good morning, everyone. Thanks for joining us this morning for our third quarter 2020 earnings call.

謝謝，凱文，大家早上好。感謝您今天早上參加我們的 2020 年第三季度財報電話會議。

Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. And also participating in today's call are Chris Boerner, our Chief Commercialization Officer; Nadim Ahmed, President, Hematology; and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development. As you note, we've posted slides to bms.com that you can follow along with Giovanni and David's remarks.

今天早上與我一起發表準備好的講話的是我們的董事會主席兼首席執行官喬瓦尼·卡福里奧 (Giovanni Caforio)；和我們的首席財務官大衛埃爾金斯。參加今天電話會議的還有我們的首席商業化官 Chris Boerner； Nadim Ahmed，血液學總裁；以及我們的首席醫療官兼全球藥物開發主管 Samit Hirawat。正如您所注意到的，我們已將幻燈片發佈到 bms.com，您可以關注喬瓦尼和大衛的評論。

And before we get going, I'll read our forward-looking statements. During this call, we'll make statements about the company's future plans and prospects that constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the company's SEC filings. These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date. We specifically disclaim any obligation to update forward-looking statements even if our estimates change.

在我們開始之前，我將閱讀我們的前瞻性聲明。在本次電話會議中，我們將就公司的未來計劃和前景發表前瞻性聲明。由於各種重要因素（包括公司提交給美國證券交易委員會的文件中討論的因素），實際結果可能與這些前瞻性陳述所示的結果存在重大差異。這些前瞻性陳述代表了我們截至目前的估計，不應被視為代表我們截至未來任何日期的估計。即使我們的估計發生變化，我們特別不承擔更新前瞻性陳述的義務。

We'll also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items. Reconciliations of those non-GAAP financial measures to the most comparable GAAP measures are available at bms.com.

我們還將重點關注我們的非公認會計準則財務指標，這些指標經過調整以排除某些特定項目。這些非 GAAP 財務指標與最具可比性的 GAAP 指標的調節表可在 bms.com 上找到。

With that, I'll hand over to Giovanni.

這樣，我就把任務交給喬瓦尼了。

Thank you, Tim, and good morning, everyone. I hope that you and your families are safe and healthy. Q3 was a very strong quarter across the company, adding to great performance over the past year. I will go into more details about the quarter in a few moments, but recognizing that it has been almost a year since we established our new company, I would first like to give you my perspective on the company overall.

謝謝蒂姆，大家早上好。我希望您和您的家人安全健康。第三季度是整個公司非常強勁的季度，為過去一年的出色業績增添了色彩。我稍後將詳細介紹本季度的情況，但考慮到我們成立新公司已經快一年了，我首先想向您介紹我對公司整體的看法。

Turning to Slide 4. A year ago, we transformed our company with the goal of positioning us for growth in the near, medium and long term. I am very pleased with our ability to consistently deliver on that promise across multiple dimensions, starting with integration, where we continue to make great progress. The strength of our execution as a combined company is a testament to our successful integration so far. The culture of our company has been shaped by our values, including a focus on innovation, collaboration and a great sense of urgency.

轉向幻燈片 4。一年前，我們對公司進行了轉型，目標是實現近期、中期和長期的增長。我對我們能夠在多個方面持續兌現這一承諾感到非常高興，從整合開始，我們繼續取得巨大進展。作為合併後的公司，我們的執行力證明了我們迄今為止的成功整合。我們公司的文化是由我們的價值觀塑造的，包括注重創新、協作和緊迫感。

Our synergy capture is ahead of our original expectations. From a commercial perspective, we have driven strong performance from our in-line brands. We have launched 4 new medicines, including Inrebic, REBLOZYL, ZEPOSIA and Onureg. We have entered the first-line lung cancer market with Opdivo and Yervoy.

我們的協同效應超出了我們最初的預期。從商業角度來看，我們的同線品牌取得了強勁的業績。我們推出了 4 個新藥，包括 Inrebic、REBLOZYL、ZEPOSIA 和 Onureg。我們以Opdivo和Yervoy進入一線肺癌市場。

In the past year, we've also delivered strongly on the potential of our pipeline, starting with immuno-oncology, where we have seen successful trials across both the metastatic and the adjuvant settings, which further supports the growth opportunity for Opdivo. Specifically, in adjuvant, Opdivo is well-positioned as a leading medicine with results in 4 different tumor types.

在過去的一年裡，我們還大力發揮了我們的產品線的潛力，從免疫腫瘤學開始，我們在轉移性和輔助治療方面都取得了成功的試驗，這進一步支持了 Opdivo 的增長機會。具體來說，在輔助治療方面，Opdivo 處於領先地位，在 4 種不同的腫瘤類型中取得了成果。

Beyond immuno-oncology, we are continuing to strengthen our presence in immunology with very encouraging data from a number of assets and programs. These include Phase III data for ZEPOSIA in ulcerative colitis, the decision to move to registrational trials for cendakimab in eosinophilic esophagitis and Phase II data for our TYK2 inhibitor, deucravacitinib in psoriatic arthritis. Most importantly, we now have top line data from our first Phase III trial for deucravacitinib in psoriasis.

除了免疫腫瘤學之外，我們還通過來自許多資產和項目的非常令人鼓舞的數據繼續加強我們在免疫學方面的影響力。其中包括 ZEPOSIA 治療潰瘍性結腸炎的 III 期數據、決定轉向 cendakimab 治療嗜酸性食管炎的註冊試驗，以及我們的 TYK2 抑製劑 deucravacitinib 治療銀屑病關節炎的 II 期數據。最重要的是，我們現在擁有 deucravacitinib 治療銀屑病的第一個 III 期試驗的主要數據。

Let me take a moment to talk about deucravacitinib. Based on the top line data that we have seen so far, we are very encouraged by the potential for this asset to be the best oral option for patients with psoriasis, with potential broad applicability across multiple diseases, including psoriatic arthritis, lupus, ulcerative colitis and Crohn's disease.

讓我花點時間談談 deucravacitinib。根據我們迄今為止看到的主要數據，我們對該資產成為銀屑病患者最佳口服選擇的潛力感到非常鼓舞，並具有在多種疾病中的潛在廣泛適用性，包括銀屑病關節炎、狼瘡、潰瘍性結腸炎和克羅恩病。

And finally, we strengthened our IP position for Revlimid and Eliquis, delivered strong financial results and continue to invest in the future with a number of important business development transactions, including 2 early-stage assets through Forbius and Dragonfly as well as the announced acquisition of MyoKardia.

最後，我們加強了 Revlimid 和 Eliquis 的知識產權地位，取得了強勁的財務業績，並通過多項重要的業務發展交易繼續投資未來，包括通過 Forbius 和 Dragonfly 進行的 2 項早期資產以及宣布收購心肌病。

Now turning to Slide 5. Through the planned acquisition of MyoKardia, we're gaining mavacamten, a potential first-in-class medicine for the treatment of obstructive hypertrophic cardiomyopathy, which is a chronic heart disease with high morbidity and patient impact.

現在轉向幻燈片 5。通過計劃收購 MyoKardia，我們將獲得 mavacamten，這是一種潛在的一流藥物，用於治療梗阻性肥厚性心肌病，這是一種發病率高、對患者影響較大的慢性心髒病。

We believe mavacamten has multibillion-dollar potential with further potential value drivers from additional indications and the MyoKardia pipeline. We look forward to closing the transaction during Q4 and welcoming our new colleagues from MyoKardia to the Bristol-Myers Squibb team.

我們相信 mavacamten 具有數十億美元的潛力，並具有來自其他適應症和 MyoKardia 管道的進一步潛在價值驅動因素。我們期待在第四季度完成交易，並歡迎來自 MyoKardia 的新同事加入百時美施貴寶團隊。

Turning to Slide 6. I am optimistic about the strategic position of our company and how we are well-positioned for growth and to navigate through the balanced cycle. Today, Bristol-Myers Squibb has significant strength and breadth in all 4 of our current therapeutic areas. Across oncology, hematology, immunology and CV, we have robust in-line businesses, exciting near-term launches as well as long-term pipeline opportunities.

轉向幻燈片 6。我對我們​​公司的戰略地位以及我們如何為增長和平衡週期做好準備持樂觀態度。如今，百時美施貴寶在我們當前的所有 4 個治療領域都擁有顯著的實力和廣度。在腫瘤學、血液學、免疫學和心血管領域，我們擁有強大的內線業務、令人興奮的近期發布以及長期管道機會。

Across all 4 areas, we are successfully building our portfolio of new medicines through a combination of short-term launches, the advancement of significant late-stage pipeline opportunities and disciplined business development.

在所有 4 個領域，我們通過短期上市、推進重要的後期管道機會和嚴格的業務發展相結合，成功構建了新藥組合。

To be more specific, Eliquis and Opdivo are assets with significant growth potential. We have 8 new medicines that are launching now or have the potential to launch over the next year. And most of these have important expansion opportunities beyond just their initial indication.

更具體地說，Eliquis 和 Opdivo 是具有巨大增長潛力的資產。我們有 8 種新藥正在上市或有可能在明年上市。其中大多數都有重要的擴展機會，超出了最初的預期。

We have gained clear line of sight to our next set of registrational assets, with 7 in or close to registrational development, including relatlimab, our 2 multiple myeloma CELMoDs, Iberdomide and CC-92480 as well as cendakimab and our Factor XIa inhibitor. And our early pipeline will continue to advance, with more than 20 assets with the potential to transition to full development over the next 3 years. Given the strength of our portfolio and pipeline, together with the talent of our people, we are focused on delivering on our full potential.

我們對下一批註冊資產有了清晰的認識，其中 7 個已處於或接近註冊開發階段，包括 relatlimab、我們的 2 種多發性骨髓瘤 CELMoD、伊貝多胺和 CC-92480 以及 cendakimab 和我們的 XIa 因子抑製劑。我們的早期開發項目將繼續推進，其中 20 多個資產有可能在未來 3 年內過渡到全面開發。鑑於我們的產品組合和產品線的實力以及我們員工的才華，我們致力於充分發揮我們的潛力。

Within that context, let me turn briefly to the strength of the quarter on Slide 7. David will provide more details, but let me discuss a few highlights from my perspective.

在此背景下，讓我簡要介紹一下幻燈片 7 中本季度的優勢。David 將提供更多詳細信息，但讓我從我的角度討論一些亮點。

First, we continue to execute very well in highly competitive markets, with sales increasing 6% compared to the same period last year on a pro forma basis. In addition, we are making good progress across our launches. And during the quarter, we have seen significant clinical progress, including multiple positive trials in I-O as well as the first Phase III trial for deucravacitinib.

首先，我們在競爭激烈的市場中繼續表現出色，預計銷售額比去年同期增長了 6%。此外，我們的產品發布也取得了良好進展。在本季度，我們看到了重大的臨床進展，包括 I-O 的多項積極試驗以及 deucravacitinib 的第一個 III 期試驗。

Based on the strength of the business, we are increasing our EPS guidance for this year and continue to be very encouraged about the earnings growth opportunity ahead as captured by our non-GAAP EPS guidance for next year, which we are reaffirming.

基於業務實力，我們正在提高今年的每股收益指引，並對明年的非公認會計原則每股收益指引所體現的未來盈利增長機會繼續感到非常鼓舞，我們正在重申這一點。

Before I hand it over to David, I want to reiterate that I'm more encouraged today than ever before about our future prospects. I can say with confidence that our company has never been stronger. Bristol-Myers Squibb is well positioned to launch multiple new medicines, new indications and benefit more patients in the very short term.

在將其交給大衛之前，我想重申，今天我對我們的未來前景比以往任何時候都更加受到鼓舞。我可以自信地說，我們的公司從未如此強大。百時美施貴寶完全有能力推出多種新藥、新適應症，並在短期內造福更多患者。

And as we look to the future, our pipeline and financial flexibility, combined with the strength and critical mass we have built across all key areas, provide us with tremendous opportunity. I'm extremely optimistic about what is to come.

展望未來，我們的渠道和財務靈活性，加上我們在所有關鍵領域建立的實力和臨界質量，為我們提供了巨大的機會。我對即將發生的事情非常樂觀。

And with that, I'll hand it over to David.

這樣，我就把它交給大衛了。

Thank you, Giovanni. Hello, everyone, and thanks again for joining our call today. I'm very pleased by the execution of our teams, delivering very strong quarterly and year-to-date results, while operating in this global pandemic.

謝謝你，喬瓦尼。大家好，再次感謝您今天加入我們的電話會議。我對我們團隊的執行力感到非常高興，在這場全球大流行的情況下，我們交付了非常強勁的季度和年初至今的業績。

Let's turn to Slide 9 and discuss our top line performance. Third quarter and year-to-date revenues continue to reflect our strong execution, growing 6% versus prior year on a pro forma basis. As you can see, a vast majority of our brands demonstrated robust growth.

讓我們轉向幻燈片 9 並討論我們的營收表現。第三季度和年初至今的收入繼續反映了我們強大的執行力，預計收入比上一年增長了 6%。正如您所看到的，我們絕大多數品牌都表現出強勁的增長。

Now let me provide additional commentary on the underlying performance of our key brands and new launches. Starting with Eliquis on Slide 10. Demand trends continue to be robust with double-digit TRx growth of 18% in the U.S. versus prior year. This demonstrates strong execution of our teams and best-in-class profile brand.

現在讓我對我們的主要品牌和新產品的基本表現進行補充評論。從幻燈片 10 上的 Eliquis 開始。需求趨勢繼續強勁，美國的 TRx 與去年相比增長了 18% 的兩位數。這體現了我們團隊的強大執行力和一流的形象品牌。

As we discussed previously, we accrue our liability related to the coverage gap as patients enter it, which affects our second half gross to net results. This is more pronounced this year as the size of the coverage gap per patient increased in 2020, and Medicare component is a larger component of our mix. This impact is in line with our expectations for Q3, and you should expect this to be a factor in the fourth quarter.

正如我們之前討論的，當患者進入保險範圍時，我們會累積與保險缺口相關的責任，這會影響我們下半年的毛淨結果。今年這種情況更加明顯，因為 2020 年每位患者的承保缺口規模有所擴大，而醫療保險部分在我們的組合中佔據了更大的組成部分。這種影響符合我們對第三季度的預期，您應該預計這將成為第四季度的一個因素。

Internationally, sales remained strong with revenue growth of approximately $1 billion, growing 22% versus prior year. Eliquis continues to be the #1 NOAC in many key markets internationally, including Germany, France and the United Kingdom. Both in the U.S. and globally, we continue to see very strong outlook for Eliquis, resulting from the strength of its profile, enabling increasing share within a growing class.

在國際範圍內，銷售依然強勁，收入增長約 10 億美元，比上年增長 22%。 Eliquis 仍然是國際許多主要市場（包括德國、法國和英國）排名第一的 NOAC。無論是在美國還是在全球範圍內，我們繼續看到 Eliquis 的前景非常強勁，這得益於其強大的形象，使其在不斷增長的類別中的份額不斷增加。

Turning to Opdivo on Slide 11. In the U.S., the teams have been executing very well. We continue to see strong shares across key indications. We now have high single-digit share in first-line lung cancer with more patients benefiting from the approvals of -227 and -9LA. And you can see that the adoption of first-line lung is reflected in the acceleration of Yervoy.

轉向幻燈片 11 上的 Opdivo。在美國，這些團隊的執行情況非常好。我們繼續看到各個關鍵指標的強勁股票。目前，我們在一線肺癌治療中所佔的比例高達個位數，更多患者受益於 -227 和 -9LA 的批准。並且可以看到一線肺的採用體現在Yervoy的加速上。

What we are really encouraged by is the return to sequential underlying growth for Opdivo. Underlying demand growth from Q2 to Q3 was approximately 2%. Sales grew 6% versus quarter 2, driven by growing underlying demand as well as the favorable customer buying patterns. We expect the impact from these buying patterns to reverse in the fourth quarter but sequential demand growth to continue, supporting our return to annual year-over-year growth for Opdivo in 2021.

我們真正感到鼓舞的是 Opdivo 恢復了連續的基本增長。第二季度至第三季度的基礎需求增長約為 2%。在潛在需求增長以及有利的客戶購買模式的推動下，銷售額比第二季度增長了 6%。我們預計這些購買模式的影響將在第四季度逆轉，但需求連續增長將繼續，支持 Opdivo 在 2021 年恢復同比增長。

Internationally, we've seen strong commercial execution across the board, with sales up 5% versus prior year. Sequentially, we saw a rebound to a stronger demand driven primarily by the European and Japanese markets as the markets continue to gain reimbursement for new indications and first-line RCC in melanoma.

在國際上，我們看到了全面強勁的商業執行力，銷售額比去年增長了 5%。隨後，我們看到主要由歐洲和日本市場推動的需求反彈至更強勁，因為市場繼續獲得黑色素瘤新適應症和一線腎細胞癌的報銷。

While there continues to be some softness in new patient starts across tumors but most notably in melanoma, we generally saw good recovery of the impact of COVID in Q3. And we also look forward to bringing Opdivo + Yervoy and limited chemotherapy to the first-line lung cancer patients in Europe this quarter.

雖然各腫瘤新患者的開始治療仍然存在一些疲軟，但最明顯的是黑色素瘤，但我們總體上看到第三季度新冠病毒的影響得到了良好的恢復。我們也期待本季度將 Opdivo + Yervoy 和有限化療帶給歐洲的一線肺癌患者。

As we look forward, we expect several additional near-term launches in 2021, including the potential for first-line gastric and several adjuvant indications such as esophageal and muscle invasive bladder cancer. And Opdivo + cabo in first-line RCC, for which we will grant a priority review. To sum things up, the teams have executed well, both commercially and clinically, which shows the continued promise for Opdivo and Yervoy and makes us even more confident in our expectations for the annual year-over-year growth in 2021.

展望未來，我們預計 2021 年還會有幾項近期上市，包括一線胃癌和食管癌和肌肉浸潤性膀胱癌等多種輔助適應症的潛力。一線RCC中的Opdivo + cabo，我們將給予優先審查。總而言之，這些團隊在商業和臨床上都表現良好，這表明 Opdivo 和 Yervoy 的持續前景，並使我們對 2021 年同比增長的預期更加充滿信心。

Moving on to our in-line multiple myeloma portfolio on Slide 12. Revlimid and Pomalyst continue to perform very well with strong double-digit growth on a pro forma basis. Revlimid grew 10% primarily driven on increased treatment duration and Pomalyst grew 17%, driven by growth in earlier lines of treatment and increased treatment duration.

接下來是幻燈片 12 上我們的多發性骨髓瘤內線產品組合。Revlimid 和 Pomalyst 繼續表現出色，預計實現強勁的兩位數增長。 Revlimid 增長了 10%，主要是由於治療持續時間的增加，Pomalyst 增長了 17%，主要是由於早期治療線的增長和治療持續時間的增加。

In the U.S., we experienced some temporary softness due to new to brand share during COVID, which is now recovering. And this is being offset by better adherence and longer duration of therapy for existing patients.

在美國，由於新冠疫情期間品牌份額出現新變化，我們經歷了一些暫時的疲軟，但目前正在恢復。而現有患者更好的依從性和更長的治療時間正在抵消這一影響。

Ex-U.S. performance sales for Revlimid increased 11%, while ex-U.S. per forma sales for Pomalyst increased 19%. This strong performance was driven by increased use of triple base therapies and treatment duration in major European markets. COVID had a minimal impact on ongoing patient treatments with a small impact observed in new patient starts. We are seeing strong signs of new patients returning to prior treatment patterns.

前美國Revlimid 的業績銷售額增長了 11%，而美國除外Pomalyst 的平均銷售額增長了 19%。這種強勁的業績得益於歐洲主要市場三基療法的使用增加和治療持續時間的增加。新冠肺炎對正在進行的患者治療的影響很小，在新患者開始治療時觀察到的影響也很小。我們看到新患者恢復先前治療模式的強烈跡象。

Now moving on to our recent launches on Slide 13. REBLOZYL has been off to a robust start with the approval of RS-positive MDS-associated anemia. Global sales in the quarter were $96 million, representing 75% sequential growth over quarter 2.

現在轉到幻燈片 13 上我們最近推出的產品。隨著 RS 陽性 MDS 相關貧血症的批准，REBLOZYL 已經有了一個強勁的開端。該季度的全球銷售額為 9600 萬美元，比第二季度環比增長 75%。

In the U.S., physician feedback remained positive with a significant awareness of the brand. While still early, we continue to be pleased with the launch, including new patient uptake and patient retention on the product, where the majority of patients have adhered to their treatment.

在美國，醫生的反饋仍然積極，對該品牌的認知度很高。雖然還為時過早，但我們仍然對產品的推出感到滿意，包括新患者的吸收和患者對產品的保留，其中大多數患者堅持了治療。

As a reminder, a significant proportion of early uptick is driven by the initial bolus of patients waiting for a new treatment option. We remain very encouraged by the underlying demand for the product in patients with beta thalassemia as well as MDS-associated anemia.

提醒一下，早期發病率上升的很大一部分是由等待新治療方案的患者的初始推注引起的。 β 地中海貧血和 MDS 相關貧血患者對該產品的潛在需求仍然令我們深受鼓舞。

Internationally, recent launches in Germany and Austria are going well although very early in the launch. We also received approval for beta thalassemia-associated anemia in Canada, and we look forward to launching in various markets globally in the course of 2021 as we receive reimbursement.

在國際上，最近在德國和奧地利的發布進展順利，儘管還處於發布初期。我們還在加拿大獲得了治療 β 地中海貧血相關貧血的批准，並期待在 2021 年在全球各個市場推出，因為我們收到了報銷。

Turning to ZEPOSIA. We're encouraged by what we are seeing through the first few months of ZEPOSIA's launch. We are focused on driving demand and establishing ZEPOSIA as the leading S1P modulator in multiple sclerosis.

轉向ZEPOSIA。我們對 ZEPOSIA 推出前幾個月所看到的情況感到鼓舞。我們致力於推動需求並將 ZEPOSIA 打造成多發性硬化症領域領先的 S1P 調節劑。

We have secured strong commercial access, and our commercial teams are executing well. We're pleased with the physician receptivity and prescription initiation we've seen thus far.

我們已經獲得了強大的商業准入，並且我們的商業團隊執行良好。我們對迄今為止所看到的醫生的接受度和處方啟動感到滿意。

Now moving on to our newest launch, Onureg, which was granted approval for first-line AML maintenance by the FDA on September 1. While very early in the launch, feedback from physicians has been promising. The message that Onureg is the first and only medicine to demonstrate overall survival in the maintenance setting with a convenient oral route of administration is resonating well. This is a market that is largely underdeveloped as there were previously no FDA-approved options for patients in the maintenance setting after intensive chemotherapy.

現在我們最新推出的 Onureg 已於 9 月 1 日獲得 FDA 批准用於一線 AML 維持治療。雖然在推出初期，醫生的反饋一直很有希望。 Onureg 是第一個也是唯一一個在維持環境中通過方便的口服給藥途徑證明總體生存率的藥物，這一信息引起了廣泛的共鳴。這是一個很大程度上尚未開發的市場，因為此前沒有 FDA 批准的針對強化化療後維持治療的患者的選擇。

And like many other medicines in the maintenance setting, it will take some time to educate prescribers about the use of new treatment for our patients. An MMA is under review in Europe, and we expect approval in 2021.

與維持環境中的許多其他藥物一樣，需要一些時間來教育處方者如何為我們的患者使用新的治療方法。歐洲正在審查 MMA，我們預計將於 2021 年獲得批准。

Now moving on to our balance sheet and capital allocation on Slide 14. We continue to generate significant amount of cash flow from operations in the third quarter. We ended the quarter in a strong liquidity position with approximately $22 billion in cash and marketable securities. That's after tax payments of approximately $1.7 billion for debt paydown and large cash payments, including tax payments associated with the gain on Otezla.

現在轉到幻燈片 14 上的資產負債表和資本配置。第三季度我們繼續從運營中產生大量現金流。本季度結束時，我們的流動性狀況良好，擁有約 220 億美元的現金和有價證券。這是扣除約 17 億美元的債務償還稅款和大筆現金支付（包括與 Otezla 收益相關的稅款）之後的結果。

Our capital allocation priorities remain unchanged, delevering and achieving less than 1.5x debt-to-EBITDA ratio, which is now expected by the end of 2024. We continued our commitment to our dividend and investing in future innovation through business development.

我們的資本配置優先事項保持不變，去槓桿化並實現債務與 EBITDA 比率低於 1.5 倍，目前預計到 2024 年底。我們繼續致力於股息並通過業務發展投資於未來創新。

To touch on our business development activities, as Giovanni discussed, we have not waivered against our priorities. We have executed some important deals over the third quarter, including our acquisition of Forbius, the license agreement with Dragonfly as well as our recently announced pending acquisition of MyoKardia. Each of these transactions is in line with our criteria for business development: strategically aligned, scientifically sound and financially attractive.

至於我們的業務發展活動，正如喬瓦尼所討論的那樣，我們並沒有放棄我們的優先事項。我們在第三季度執行了一些重要交易，包括收購 Forbius、與 Dragonfly 的許可協議以及我們最近宣布的即將收購的 MyoKardia。這些交易中的每一項都符合我們的業務發展標準：戰略一致、科學合理且具有財務吸引力。

We will continue to be active in business development, searching for additional opportunities to further strengthen our growth profile for the company for the long term and creating value for our shareholders.

我們將繼續積極發展業務，尋找更多機會，進一步增強公司的長期增長前景，並為股東創造價值。

Now let's turn to guidance on Slide 15. Based on the strength of our results year-to-date, we are updating our full year 2020 outlook. We are narrowing our revenue range to between $41.5 billion and $42 billion based upon the strong performance year-to-date. And we do expect sales to be at the higher end of the range.

現在讓我們轉向幻燈片 15 的指導。根據我們今年迄今的強勁業績，我們正在更新 2020 年全年展望。基於今年迄今為止的強勁業績，我們將收入範圍縮小至 415 億美元至 420 億美元之間。我們確實預計銷售額將處於該範圍的高端。

Turning to operating expenses. We expect total spend to be generally in line with our expectations. We do have some slight shifts in spend related to our MS&A and R&D lines. For MS&A, we decided to make additional onetime investment such as accelerating DTC advertising to support the business as we close out the year, and we now expect to spend approximately $6.9 billion. This is being offset by lower R&D expense, now expected to be approximately $9.2 billion.

轉向運營費用。我們預計總支出將基本符合我們的預期。我們確實在與 MS&A 和研發線相關的支出方面發生了一些細微的變化。對於 MS&A，我們決定進行額外的一次性投資，例如在年底時加速 DTC 廣告以支持業務，我們現在預計支出約 69 億美元。這被較低的研發費用所抵消，目前預計約為 92 億美元。

At the same time, we remain very pleased with our synergy capture, which, as Giovanni mentioned, is tracking ahead of our original expectations. We now expect our tax rate to be approximately 16% for the full year. And taking all this together, we are increasing our full year adjusted EPS range to be between $6.25 and $6.35 per share.

與此同時，我們仍然對我們的協同效應感到非常滿意，正如喬瓦尼所提到的，這超出了我們最初的預期。我們現在預計全年稅率約為 16%。綜合考慮所有這些因素，我們將全年調整後每股收益範圍提高到每股 6.25 美元至 6.35 美元之間。

Our revenue guidance takes into account (inaudible), which continues to affect Eliquis in the fourth quarter, as I mentioned earlier as well as continued competitive dynamics associated with some of our established brands. Now as it relates to our 2021 guidance, we are reaffirming our non-GAAP EPS guidance of $7.15 to $7.45, which absorbs the dilution associated with the MyoKardia acquisition. We look forward to providing more color on 2021 during our fourth quarter call as we normally do.

正如我之前提到的，我們的收入指引考慮了（聽不清），這將繼續影響第四季度的 Eliquis，以及與我們一些知名品牌相關的持續競爭動態。現在，由於與我們的 2021 年指導相關，我們重申我們的非 GAAP 每股收益指導為 7.15 美元至 7.45 美元，這吸收了與 MyoKardia 收購相關的稀釋。我們期待像往常一樣在第四季度電話會議上提供有關 2021 年的更多信息。

Before we move to question-and-answer, I want to thank all of our teams around the world for delivering such outstanding results year-to-date. These results allow me to remain confident in the long-term outlook for the company.

在我們開始問答之前，我要感謝我們世界各地的所有團隊今年迄今為止取得瞭如此出色的成果。這些結果讓我對公司的長期前景保持信心。

I'll now turn the call back over to Tim and Giovanni for Q&A.

我現在將把電話轉回蒂姆和喬瓦尼進行問答。

Great. Thanks very much, David. Kevin, can we go to our first question, please?

偉大的。非常感謝，大衛。凱文，我們可以回答第一個問題嗎？

(Operator Instructions) Our first question today comes from Chris Schott of JPMorgan.

（操作員指令）我們今天的第一個問題來自摩根大通的 Chris Schott。

Congrats on all the progress you've made this year. I guess just 2 here. Maybe first on the TYK2. Can you just elaborate a little bit more on the safety profile? I think there's still some lingering questions out there. Will we see any of maybe some of the JAK-like safety issues? I know you've talked a lot about that in the past.

祝賀您今年取得的所有進步。我猜這裡只有 2 個。也許首先是 TYK2。您能詳細說明一下安全性嗎？我認為仍然存在一些揮之不去的問題。我們會看到任何類似 JAK 的安全問題嗎？我知道你過去已經談論過很多這個問題。

But just to confirm, did you see any imbalance at all, small or not, on thrombotic events from the POETYK study? And just help us a little bit in terms of what the profile is shaping up like on the safety there.

但我想確認一下，您在 POETYK 研究中是否發現血栓事件存在任何不平衡，無論大小？請幫助我們了解那裡的安全狀況。

And then my second question was on Opdivo. You're launching a number of adjuvant indications next year. Can you remind us on those, do you expect these will have fast uptake like we're seeing in some of the metastatic settings? Or are these indications that maybe take a little bit longer to build out over time?

我的第二個問題是關於 Opdivo 的。你們明年將推出多種輔助適應症。您能否提醒我們，您是否期望這些藥物會像我們在某些​​轉移性環境中看到的那樣快速被吸收？或者這些跡像是否可能需要更長的時間才能隨著時間的推移而顯現出來？

Chris, thank you. I think I'll start off and then Chris, I'll pass it on to you for Opdivo-related question. From a TYK2 perspective, first of all, we are very happy with what we've seen from the results perspective. It is the first of the 2 Phase III trials for TYK1 that has read out. And we have seen not only topical as well as clinical meaningfulness versus placebo, but also the superiority versus apremilast or Otezla in moderate to severe psoriasis.

克里斯，謝謝你。我想我會開始，然後克里斯，我會將與 Opdivo 相關的問題轉交給您。從 TYK2 的角度來看，首先，我們對所看到的結果感到非常滿意。這是 TYK1 的 2 項 III 期試驗中的第一項。我們不僅看到了與安慰劑相比的局部和臨床意義，而且還看到了在中度至重度銀屑病中相對於阿普斯特或 Otezla 的優越性。

From what we have seen before from the Phase II studies and we've talked about the safety profile, we continue to believe in that. There is a differentiated mechanism of action that we believe in. We do think that the TYK2 inhibition, which has a specific downstream effect on IL-12, IL-23 as well as interferon alpha has played out, and we continue to believe in that.

從我們之前從二期研究中看到的情況以及我們討論過的安全性來看，我們仍然相信這一點。我們相信存在一種差異化的作用機制。我們確實認為 TYK2 抑製作用（對 IL-12、IL-23 以及乾擾素 α 具有特定的下游作用）已經發揮作用，並且我們仍然相信。

Of course, I can't go into the specifics of the data. They will be presented in the future in the macro meeting. But overall, we are very happy where we are, and I look forward to the readout of the second Phase III in the first quarter of 2021. So hopefully, that answers your question, and let me pass it on to Chris to talk about Opdivo from here on.

當然，我不能透露具體的數據。它們將在未來的宏觀會議上呈現。但總的來說，我們對目前的情況感到非常滿意，我期待著 2021 年第一季度第二個 III 期試驗的結果。希望這能回答您的問題，讓我將其轉交給 Chris 來談談 Opdivo從現在開始。

Sure. Thanks for the question, Chris. We do have a number of exciting opportunities in the adjuvant setting, and maybe I'll just highlight gastric and bladder, specifically. As we talked about a few months ago with respect to gastric cancer, we're excited about the opportunity coming out of CheckMate -577. This is a space where there's significant unmet need as very little in the way of systemic therapy that's used here. And as Samit has previously talked about, those patients who are getting neoadjuvant chemo radiotherapy, about 3/4 of those patients don't get a PAT CR. So really, there are no great options for those patients. And we've seen very good efficacy coming out of -577, with the doubling of DFS at a manageable safety profile. And there's relative clean air here from a competitive standpoint as we'll be the first I-O in the setting for a number of years.

當然。謝謝你的提問，克里斯。我們在輔助治療方面確實有許多令人興奮的機會，也許我會特別強調胃和膀胱。正如我們幾個月前談到的有關胃癌的內容，我們對 CheckMate -577 帶來的機會感到興奮。這是一個存在大量未滿足需求的領域，因為這裡使用的系統治療方式很少。正如 Samit 之前談到的，那些接受新輔助化療放療的患者中，大約有 3/4 的患者沒有獲得 PAT CR。所以說實話，對於這些患者來說沒有什麼好的選擇。我們已經看到 -577 具有非常好的功效，DFS 在可控的安全性下增加了一倍。從競爭的角度來看，這裡的空氣相對乾淨，因為我們將成為多年來該地區的第一個 I-O。

With respect to bladder, again, happy with the results that we saw with -274. This is a space with about 6,000 to 7,000 treated patients in the U.S. Again, not a lot in the way of great systemic therapies here. And as we've said, we met the primary end point for Opdivo and very much look forward to launching in the space. And this is, again, another space where there's relative clean air. So we would expect a reasonably aggressive uptake in both of these indications.

關於膀胱，再次對我們看到的 -274 的結果感到滿意。在美國，這個領域約有 6,000 至 7,000 名接受治療的患者。同樣，這裡的系統治療方法並不多。正如我們所說，我們已經達到了 Opdivo 的主要終點，並且非常期待在該領域推出。這又是另一個空氣相對乾淨的空間。因此，我們預計這兩個適應症都會得到相當積極的採用。

The next question today comes from Seamus Fernandez of Guggenheim.

今天的下一個問題來自古根海姆的謝默斯·費爾南德斯。

Congrats on the quarter and all the progress as well. Samit, my question is actually on the higher dose, the 12-milligram dose, that we're going to see next week in psoriatic arthritis. Can you just give us -- that's really where we've seen problems with other JAKs. Just trying to get your sense of what we should be looking for in those data. Obviously, they're about to be presented, but I think that's something that investors are interested in.

祝賀本季度和所有進展。 Samit，我的問題實際上是關於下週我們將在銀屑病關節炎中看到的更高劑量，即 12 毫克劑量。您能否告訴我們——這確實是我們在其他 JAK 中看到的問題所在。只是想讓您了解我們應該在這些數據中尋找什麼。顯然，它們即將被展示，但我認為這是投資者感興趣的事情。

And then incremental to that, as we think about the opportunity in areas like ulcerative colitis, you've really emphasized this IL-23 -- -12, -23 profile, is that really where your enthusiasm for the product is in ulcerative colitis in particular?

然後增量，當我們考慮潰瘍性結腸炎等領域的機會時，您確實強調了 IL-23 -- -12、-23 概況，這正是您對潰瘍性結腸炎產品的熱情所在特別的？

Thank you, Seamus, for the question and quite appropriate, in fact. When we look at the POETYK 1 readout as we said in the press release, the dose used in the Phase III trial is the 6-milligram dose. And what you have in the abstract and the poster at the ACR for ulcerative colitis, as we mentioned, are both 6 and the 12 milligrams dose.

謝謝謝莫斯提出這個問題，事實上，這個問題非常恰當。正如我們在新聞稿中所說，當我們查看 POETYK 1 讀數時，III 期試驗中使用的劑量是 6 毫克劑量。正如我們提到的，摘要和 ACR 上針對潰瘍性結腸炎的海報都是 6 毫克和 12 毫克劑量。

We do see a profile from a safety perspective of the 6-milligram dose as we talked about. Also in looking at the older Phase II study, generally very good in that dose, and that's the efficacy we have now seen in the Phase III study as well.

正如我們所討論的，我們確實從安全角度看到了 6 毫克劑量的概況。另外，從較早的 II 期研究來看，該劑量通常非常好，這也是我們現在在 III 期研究中看到的功效。

At the 12-milligram dose, we do see a dose response. But then you have to keep in mind as you very correctly said, the overall safety management results. So we'll continue to dig deeper into the data as we plan Phase III study in the ulcerative colitis space. But overall, we are very happy with the dose that we have tested in the Phase II study. And of course, as I said earlier, we’ll look at it again, in the Phase III -- the second readout in the first quarter of next year as we move forward.

在 12 毫克劑量下，我們確實看到了劑量反應。但是，正如您所說，您必須牢記整體安全管理結果。因此，當我們計劃在潰瘍性結腸炎領域進行 III 期研究時，我們將繼續深入挖掘數據。但總的來說，我們對 II 期研究中測試的劑量非常滿意。當然，正如我之前所說，我們將在第三階段再次審視它——隨著我們的前進，明年第一季度的第二次讀數。

So that's, I think, the differentiation that it's not just about efficacy. We have to balance the benefit risk. And that's why the 6-milligram dose is quite reasonable for us from a safety and efficacy combined benefit ratio. As it relates to the ulcerative colitis, the mechanism as we very well said, I think the differentiation, the oral administration, the convenience of treatment, we've talked about ulcerative colitis with ZEPOSIA already, and now we are looking towards readout in the future for the TYK2 program.

所以，我認為，這就是區別，它不僅僅是功效。我們必須平衡利益風險。這就是為什麼從安全性和有效性綜合效益比來看，6 毫克劑量對我們來說是相當合理的。因為它與潰瘍性結腸炎有關，正如我們說得很好的機制，我認為分化、口服給藥、治療的便利性，我們已經用 ZEPOSIA 討論了潰瘍性結腸炎，現在我們正在尋找在TYK2 計劃的未來。

And bringing that differentiated mechanism once again and hopefully, be able to show the efficacy and safety for patients with ulcerative colitis with TYK2 will be important. And yes, IL-12 and IL-23, in addition to mechanism, is going to play a big role both in ulcerative colitis and then in the future in Crohn's disease as well.

再次帶來這種差異化機制，希望能夠證明 TYK2 對潰瘍性結腸炎患者的有效性和安全性將非常重要。是的，除了機制之外，IL-12 和 IL-23 將在潰瘍性結腸炎以及未來的克羅恩病中發揮重要作用。

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

你的下一個問題來自美國銀行的傑夫·米查姆。

Great. Just had a couple, I think both of them for Chris. So when you look at the first-line lung trend for Opdivo, Chris, you guys have gained some share, I think, 5% or so in the U.S., but I don't see much of a trend break this quarter. Was there already reasonable share in first-line lung before the label expansion? And maybe just help us to what's been the feedback from the ground so far?

偉大的。剛剛喝了幾個，我想他們都是克里斯的。所以，克里斯，當你看看 Opdivo 的一線肺部趨勢時，你們在美國獲得了一些份額，我認為是 5% 左右，但我認為本季度趨勢不會有太大突破。在標籤擴展之前，一線肺部藥物是否已經有合理的份額？也許只是幫助我們了解到目前為止來自地面的反饋是什麼？

And the second one on REBLOZYL, the sequential trends have been really strong. I know obviously it's early. But what can you say about the distribution between MDS and beta thal and maybe just the cadence of uptick between the 2 indications?

REBLOZYL 的第二個趨勢非常強勁。我知道顯然還早。但是，您對 MDS 和 beta thal 之間的分佈以及這兩種適應症之間的上升節奏有何看法？

Maybe I'll start, and then I'll turn it over to Nadim to address the second part of your question. So with respect to Opdivo, let me just first give you the dynamics for the quarter. So obviously happy with the sequential growth that we saw for the quarter. On that, in the U.S., is a function of favorable demand, and I'll talk about first-line lung, specifically in a second.

也許我會開始，然後我會將其交給納迪姆來解決你問題的第二部分。因此，關於 Opdivo，讓我首先向您介紹本季度的動態。顯然我們對本季度的連續增長感到滿意。在美國，這是有利需求的函數，我將討論一線肺，特別是在第二線。

We also, as David had noted, saw some inventory build. This was partially offset by the impact that we've seen with the decline in I-O eligibility that we've been discussing previously. That's mainly in the second-line thoracic indications. And that still is a drag on Opdivo currently.

正如大衛所指出的，我們還看到了一些庫存的增加。我們之前討論過的 I-O 資格下降帶來的影響部分抵消了這一影響。這主要是二線胸部適應症。目前，這仍然是 Opdivo 的一個拖累。

That said, we were happy to see that we got sequential growth for the quarter, and that was, in part, a function of first-line lung. And with respect to first-line lung, we're very happy with what we're seeing with the launches so far in the U.S. The uptake continues to increase steadily.

也就是說，我們很高興看到本季度實現連續增長，這在一定程度上是一線肺的功能。就一線肺治療而言，我們對迄今為止在美國的上市情況感到非常滿意，其使用量繼續穩步增長。

As we noted earlier, the market share is currently in the high single digits. The execution here continues to be very good. So for example, we have a leading share of voice in first-line lung.

正如我們之前指出的，市場份額目前處於較高的個位數。這裡的執行仍然非常好。例如，我們在一線肺部擁有領先的話語權。

And importantly, at this stage of the launch, we're seeing a nice steady growth in the number of new trials week-over-week. So overall, we're happy with the uptake that we've seen. We knew as we discussed previously that this was going to be a different set of launches just given the entrenched dynamics from a competitive standpoint in first-line lung, but we continue to be very pleased with the team's performance here. So maybe I'll turn it over to Nadim for the second part of your question.

重要的是，在發布的這個階段，我們看到新試驗的數量每週都在穩步增長。總的來說，我們對所看到的採用率感到滿意。正如我們之前討論的那樣，我們知道這將是一組不同的發布，只是考慮到從一線肺的競爭角度來看根深蒂固的動態，但我們仍然對團隊在這裡的表現感到非常滿意。所以也許我會把它交給納迪姆來回答你問題的第二部分。

Great. Thanks, Geoff, for your question. So regarding the REBLOZYL launch, maybe I'll just make a couple of points. So as David said, very pleased with the launch so far, high demand, very good brand awareness. Field team is doing really well.

偉大的。謝謝杰夫提出的問題。關於 REBLOZYL 的發布，也許我只想說幾點。正如大衛所說，到目前為止，我們對產品的推出感到非常滿意，需求量很大，品牌知名度非常高。現場團隊做得非常好。

And if you remember, we had always said that the predominant use, at least in the U.S., would be MDS, and it's playing out exactly that same way. So today, the majority use in the U.S. is on MDS patients. And the interesting thing is we've seen a little bit of a halo effect on beta thal in that we've seen a little bit more uptake with beta thal since the MDS launch, but the predominant use is still MDS.

如果您還記得的話，我們一直說過，至少在美國，主要用途是 MDS，而且情況也是如此。因此，目前在美國，該藥物的主要治療對像是骨髓增生異常綜合徵 (MDS) 患者。有趣的是，自 MDS 推出以來，我們看到了 beta thal 的一些光環效應，因為我們看到了 beta thal 的使用量有所增加，但主要用途仍然是 MDS。

Now globally, as we launch across the world, there will be different regions where you see a different prevalence profile, beta thalassemia, where it's higher, for example, in Asia, the Mediterranean. But today in the U.S., Geoff, the predominant use is still MDS, exactly as we had anticipated. Thanks for your question.

現在在全球範圍內，當我們在世界各地推出時，您會在不同的地區看到不同的患病率，β地中海貧血的患病率較高，例如在亞洲、地中海。但傑夫，今天在美國，主要用途仍然是 MDS，正如我們所預期的那樣。謝謝你的提問。

The next question comes from Terence Flynn of Goldman Sachs.

下一個問題來自高盛的特倫斯·弗林。

I was just wondering first, on Opdivo for neoadjuvant lung. If you can give us any update on the regulatory path and when you might know more there and if you're confident that you could get approval on the PCR endpoint alone.

我首先想知道 Opdivo 用於新輔助肺治療。如果您可以向我們提供有關監管路徑的任何最新信息，以及您何時可能了解更多信息，以及您是否有信心僅在 PCR 終點上就能獲得批准。

And then the second question, you mentioned that the synergies are tracking ahead of your expectations. I guess just trying to understand how much of the spend is synergies, and how much is kind of from a COVID environment? And so how much of that should we expect to carry forward into 2021?

第二個問題，您提到協同效應的進展超出了您的預期。我想只是想了解有多少支出是協同效應，有多少支出是來自新冠疫情環境？那麼我們應該期望將其中多少延續到 2021 年呢？

Thank you, Terence, for the question. Samit here. As Chris mentioned earlier, there is still obviously a much required need for new medicines in patients with early disease to be able to get into a complete response because that may signal for the long-term benefit for these patients.

謝謝特倫斯提出的問題。薩米特在這裡。正如克里斯之前提到的，早期疾病患者顯然仍然非常需要新藥才能獲得完全緩解，因為這可能預示著這些患者的長期受益。

Now of course, this is not a validated regulatory endpoint as you very well said. So what we are looking forward to now, of course, continuing our dialogue with the regulatory agency, especially with the FDA, as we also continue to follow these patients for the first data for event-free survival as well. So we will obviously keep you posted in the future as we make progress.

當然，正如您所說，這並不是一個經過驗證的監管終點。當然，我們現在期待的是繼續與監管機構，特別是 FDA 的對話，因為我們還將繼續跟踪這些患者，以獲得無事件生存的第一個數據。因此，隨著我們取得進展，我們顯然會在未來隨時向您通報情況。

At the current time, we continue our dialogue and continue with the patient follow-up to generate more data. I don't think we can give a clear guidance today in terms of approvability based on the endpoint. And for synergies, I think David or…

目前，我們繼續對話並繼續對患者進行隨訪以生成更多數據。我認為我們今天無法在基於端點的可批准性方面給出明確的指導。為了協同作用，我認為大衛或......

Yes. I can. Thanks for the question. Look, we've been very pleased with our ability to capture synergies so far this year, and we're really encouraged to see that our synergy capture is actually tracking ahead of our original expectations for this year. So we'll provide further insight to that on our expectations of the overall synergy achievement after we close the year, but things are going very well.

是的。我可以。謝謝你的提問。看，我們對今年迄今為止獲得協同效應的能力感到非常滿意，並且我們真的很高興看到我們的協同效應實際上超出了我們今年的最初預期。因此，我們將在年底後進一步深入了解我們對整體協同效應成就的期望，但事情進展順利。

The next question comes from Tim Anderson of Wolfe Research.

下一個問題來自沃爾夫研究中心的蒂姆·安德森。

I have a question on going back to TYK2. So I think most investors view the value proposition in psoriasis relative to Otezla as being better efficacy. But we've wondered if better tolerability could also be a differentiator because with Otezla, there's GI side effects that require dose titration, and your drug doesn't require dose titration. At least in Phase II, there were no GI side effects. So when we see the full Phase III results, might we also see better tolerability as yet another area of differentiation beyond just oral dosing and beyond better efficacy?

我有一個關於回到 TYK2 的問題。因此，我認為大多數投資者認為牛皮癬相對於 Otezla 的價值主張具有更好的功效。但我們想知道更好的耐受性是否也可能是一個差異化因素，因為 Otezla 存在胃腸道副作用，需要劑量滴定，而您的藥物不需要劑量滴定。至少在第二階段，沒有出現胃腸道副作用。因此，當我們看到完整的 III 期結果時，我們是否還會看到更好的耐受性，作為除了口服給藥和更好的療效之外的另一個差異化領域？

Thank you, Tim, for the question. As we said, if you look at the overall trial design for this one as well as for the next study to be followed, the good news is that there is a comparison not only versus placebo but also the comparison versus Otezla. And so there will certainly be an opportunity to contrast and compare not only the efficacy, but also the tolerability or safety as we talk about. And those are going to be very important from a patient perspective and physician perspective, from a convenience perspective. Certainly, these will have implications from a commercial perspective, and let me pass it on to Chris to comment on that.

謝謝蒂姆提出的問題。正如我們所說，如果您查看本次試驗的總體試驗設計以及接下來的下一項研究，好消息是不僅與安慰劑進行比較，還與 Otezla 進行比較。因此，肯定會有機會對比和比較我們所討論的不僅是療效，還有耐受性或安全性。從患者和醫生的角度以及便利的角度來看，這些都將非常重要。當然，從商業角度來看，這些都會產生影響，讓我將其轉告克里斯對此發表評論。

Yes. Thanks for the question, Tim. I mean, I think as we've said previously, we're excited with the opportunity that we have here. Based on the data that we see coming out of POETYK, I think we have a real opportunity to establish TYK as the frontline branded oral of choice for these moderate to severe patients.

是的。謝謝你的提問，蒂姆。我的意思是，我認為正如我們之前所說，我們對這裡擁有的機會感到興奮。根據我們從 POETYK 獲得的數據，我認為我們確實有機會將 TYK 打造成這些中度至重度患者首選的一線品牌口服藥物。

What I would say just to build on what Samit mentioned is that this is a market where in spite of new biologics coming into the space, dermatologists continue to believe in an ascending treatment algorithm. So they typically start with topical, they move to orals, then they go to injectables.

在薩米特提到的基礎上，我想說的是，儘管有新的生物製劑進入該領域，但皮膚科醫生仍然相信不斷進步的治療算法。因此，他們通常從局部用藥開始，然後轉向口服，然後再轉向注射。

And it is also a market, as I think you point out, where patient preference drives choice. So you do see a very strong focus on safety concerns, needle phobia is an issue here. And we think these dynamics really play to the profile that we have with TYK2, very strong efficacy in an oral formulation, a novel MOA and a favorable tolerability and safety profile. And so we think we've got real opportunity here to establish TYK as the leading oral in the space.

正如我認為你指出的那樣，這也是一個患者偏好驅動選擇的市場。所以你確實看到了人們對安全問題的強烈關注，針頭恐懼症是這裡的一個問題。我們認為這些動態確實符合 TYK2 的特點，口服製劑具有很強的功效、新穎的 MOA 以及良好的耐受性和安全性。因此，我們認為我們有真正的機會將 TYK 打造為該領域領先的口頭表達者。

The next question comes from Andrew Baum of Citi.

下一個問題來自花旗銀行的安德魯·鮑姆。

Couple of questions, please. First on Otezla. As you think about marketing, is it positioned to displace Otezla as the oral agent of choice, given the efficacy tolerability? Or to what extent can you actually seek to slow or defer the initiation of therapy with biologics? And then second, perhaps you could just give us the market shares in non-small cell for -227, -9LA in the U.S. in the first-line setting.

請教幾個問題。首先是奧特茲拉。當您考慮營銷時，考慮到功效耐受性，它是否能夠取代 Otezla 成為首選口服藥物？或者您實際上可以在多大程度上減緩或推遲生物製劑治療的開始？其次，也許您可以向我們提供美國一線環境中-227、-9LA 非小型基站的市場份額。

Chris?

克里斯？

Sure. Sure. Andrew, thanks for the question. With respect to Otezla and how we are looking at the TYK opportunity in psoriasis, I mean I think the way I answered the previous question is probably what I would go back to. We think based on these data that TYK has the opportunity to be the branded oral of choice for moderate-to-severe patients writ large in this space.

當然。當然。安德魯，謝謝你的提問。關於 Otezla 以及我們如何看待 TYK 在牛皮癬領域的機會，我的意思是，我認為我回答前一個問題的方式可能是我會回去的。我們認為，基於這些數據，TYK 有機會成為該領域中中重度患者的首選品牌口服產品。

And we think that's a reflection of the fact that this is a market where dermatologists typically are going to try to treat with less burdensome routes of administration. They're going to go for the activity that -- the best activity they can find.

我們認為這反映了這樣一個事實：皮膚科醫生通常會嘗試用不太繁瑣的給藥途徑來治療這個市場。他們會去參加他們能找到的最好的活動。

However, safety is a prominent concern here. And so I think that we have the opportunity to displace existing therapy with respect to orals prebiologic. And we also believe that we have the opportunity to potentially provide more of an opportunity before patients move on to biologics.

然而，安全是這裡的一個突出問題。因此，我認為我們有機會取代口服益生元方面的現有療法。我們還相信，在患者轉向生物製劑之前，我們有機會提供更多的機會。

And remember, this is a space where only about 15% of patients ultimately ever get to biologics, and that's in spite of a number of new biologics coming into the market. So we think we actually have an opportunity to do both.

請記住，儘管有許多新的生物製劑進入市場，但只有約 15% 的患者最終會使用生物製劑。所以我們認為我們實際上有機會做到這兩點。

As it relates to the first-line lung market share, as we said previously and as David mentioned, we have current first-line market share in the high single digits. The -227 regimen is mainly being used in the PD-L1 to -49 as expected. And then we're seeing recent uptake of the -9LA regimen, and that's mainly in the PD-L1 less than 1 and PD-L1 negatives.

由於它與一線肺臟市場份額有關，正如我們之前所說和大衛提到的，我們目前的一線市場份額處於高個位數。正如預期的那樣，-227方案主要用於PD-L1至-49。然後我們看到最近 -9LA 方案的採用，主要是 PD-L1 小於 1 和 PD-L1 陰性。

The next question comes from Luisa Hector of Berenberg.

下一個問題來自貝倫貝格的路易莎·赫克托。

I wonder now we have the ASH abstract, whether there's anything you'd like to point out from the various data sets you're presenting and any particular update from durability of response? And then ide-cel and liso-cel, any update you can give us on the FDA review?

我想知道現在我們有了 ASH 摘要，您是否想從您提供的各種數據集中指出任何內容，以及響應持久性的任何特定更新？然後是 ide-cel 和 liso-cel，您能給我們提供有關 FDA 審查的任何更新嗎？

Sure. Thank you. So let me start with ASH first, and then I'll go to the liso-cel, ide-cel. And then certainly, if Nadim wants to comment also that will be wonderful.

當然。謝謝。所以讓我先從 ASH 開始，然後再講 liso-cel、ide-cel。當然，如果納迪姆也想發表評論，那就太好了。

So for ASH perspective, over the last few years, certainly, both Celgene and (inaudible) as well as the (inaudible) had beta presence. And based on the data that have been presented in the past, so obviously these medicines have now moved on to late-stage development, and we are continuing to gather more data.

因此，從 ASH 的角度來看，在過去幾年中，Celgene 和（聽不清）以及（聽不清）都存在測試版。根據過去提供的數據，顯然這些藥物現在已經進入後期開發，我們正在繼續收集更多數據。

Having said that, there are a few abstracts that are very important that are being presented. So number one, the activity of liso-cel, the single therapy as well as in combination where the patients who received guided (inaudible), both in CLL, are quite important and interesting.

話雖如此，有一些非常重要的摘要正在呈現。因此，第一，liso-cel 的活性、單一療法以及接受指導（聽不清）的 CLL 患者的聯合療法，都是非常重要和有趣的。

If you look at the overall response rate positivity as well as durability in these patients, that continue to evolve, especially as you think of the future where the population with CLL where patients with CLL have been treated with ibrutinib and venetoclax, there will be a need for subsequent therapy that will rescue them if the disease has a recurrence or relapse.

如果您觀察這些患者的整體緩解率積極性以及持續發展，尤其是當您考慮到未來 CLL 患者接受依魯替尼和維奈托克治療的 CLL 人群時，將會有如果疾病復發，則需要後續治療來挽救他們。

Another data set will be presented as you might have seen in the abstracts will be the triple combination of Iberdomide with daratumumab as well as dexamethasone and then VELCADE and dexamethasone. And those are evolutions in the data set, and we'll continue to see how that comes through, but certainly, response rates are going to be important as we look forward to moving Iberdomide into the earlier settings as these data will then start dictating how we proceed further.

正如您可能在摘要中看到的那樣，將呈現的另一個數據集是伊貝多胺與達雷妥尤單抗、地塞米松以及 VELCADE 和地塞米鬆的三聯組合。這些是數據集中的演變，我們將繼續看到它是如何實現的，但當然，響應率將很重要，因為我們期待將伊貝多米德轉移到早期設置，因為這些數據將開始決定如何我們繼續前進。

So very happy with these. We'll continue to look deeper into it and next year will be big from a CELMoDs perspective as we look to the completion of the trials for Iberdomide and then, of course, progressing other CELMoDs as you heard from Giovanni in his opening comments.

對這些非常滿意。我們將繼續深入研究它，從 CELMoD 的角度來看，明年將是重要的一年，因為我們期待完成 Iberdomide 的試驗，然後，當然，正如您在 Giovanni 的開場評論中聽到的那樣，也將推進其他 CELMoD。

From liso-cel perspective, not much to share except for the fact that we've already communicated. We continue our dialogue with the regulatory agencies. We've had the inspection done for the facility in Washington. And as we have communicated earlier that we don't have any scheduled inspections for the second facility, which is one -- which is independent of the other facility.

從 liso-cel 的角度來看，除了我們已經溝通過的事實之外，沒有什麼可分享的。我們繼續與監管機構對話。我們已經對華盛頓的設施進行了檢查。正如我們之前所傳達的，我們沒有對第二個設施進行任何計劃檢查，這是一個獨立於另一個設施的設施。

For liso-cel, we do have a PDUFA date on 16th of November. For ide-cel, same thing, we are continuing our dialogue and that we have PDUFA date of March 27, 2021. That's where we are. I don't know, Nadim, if you want to add something or Giovanni?

對於 liso-cel，我們的 PDUFA 日期是 11 月 16 日。對於 ide-cel，同樣的事情，我們正在繼續對話，我們的 PDUFA 日期為 2021 年 3 月 27 日。這就是我們現在的情況。我不知道，納迪姆，你是否想補充一些東西，或者喬瓦尼？

No. I think you covered it well, Samit. Thanks.

不，我認為你講得很好，薩米特。謝謝。

The only thing I would add is -- this is Giovanni. The only thing I would add is just to close on what Samit mentioned with respect to liso-cel. As always obviously we will update you as our discussion with the regulatory authorities progress.

我唯一要補充的是——這是喬瓦尼。我唯一要補充的就是結束 Samit 提到的有關 liso-cel 的內容。與往常一樣，隨著我們與監管機構的討論取得進展，我們將向您通報最新情況。

Next question comes from Dane Leone of Raymond James.

下一個問題來自 Raymond James 的 Dane Leone。

Congratulations on all the progress. Just some quick ones for me. When do you think you would be able to disclose the actual pathologic complete response rate for the 816 study? And if that would still be a nondisclosure item for you until regulatory discussions are complete.

祝賀所有的進展。對我來說只是一些快速的。您認為什麼時候能夠披露 816 研究的實際病理完全緩解率？在監管討論完成之前，這對您來說是否仍然是一個保密項目。

Could you at least give us how the study was powered on that endpoint, so we can make our own assumptions on how the chemo arm would perform and then how the combo arm probably would have performed to (inaudible).

您能否至少告訴我們該研究是如何在該終點上進行的，以便我們可以對化療臂的表現以及組合臂可能的表現做出自己的假設（聽不清）。

And then in terms of Iberdomide, do you have a longer time line now in terms of path to pivotal studies and when that could actually get to market? I think a lot of us in the clinical community as well are thinking about this as an offset to Revlimid and the patent expirations there. So any kind of longer-term insight you might be able -- given the development path would be super helpful.

那麼就伊貝多胺而言，您現在在關鍵研究路徑方面是否有更長的時間線以及何時可以真正進入市場？我認為臨床界的很多人也都認為這是對 Revlimid 和專利到期的補償。因此，考慮到發展路徑，您可能擁有的任何長期洞察力都會非常有幫助。

Thank you for the question. So let me start with the PCR part. So certainly, we're going to look for an opportunity for a tougher presentation of the data at a future medical meeting. That is not dependent on the regulatory aspects because it's an independent endpoint that can certainly be discussed. So we're looking to that.

感謝你的提問。那麼讓我從 PCR 部分開始。因此，當然，我們將尋找機會在未來的醫學會議上更嚴格地展示數據。這不依賴於監管方面，因為它是一個當然可以討論的獨立終點。所以我們正在尋找這一點。

I think the trial details, we have not shared the statistical analysis plan per se in terms of the assumptions made for the calculation at this time. So we'll not be able to share that. But certainly, there is a previous data that had been presented and published for chemotherapy leading to PCR responses so we can assume with that.

我認為試驗細節，我們目前還沒有就計算假設來分享統計分析計劃本身。所以我們無法分享這一點。但當然，之前已經提出並發表了化療導致 PCR 反應的數據，因此我們可以對此進行假設。

Now what differences will be important in terms of the delta between chemotherapy and then the combination of nivolumab? Those are the types of discussions we'll need to continue to have with the regulatory agency as to what becomes meaningful. So as the dialogue evolves and once the decisions are made, we'll certainly communicate that with you.

現在，化療與納武單抗聯合治療之間的差異有哪些重要？這些是我們需要繼續與監管機構進行的討論，以了解什麼是有意義的。因此，隨著對話的進展以及一旦做出決定，我們一定會與您溝通。

From the Iberdomide perspective, the fourth-line cost study is already ongoing as we said. And as I've just mentioned previously, as the data continues to evolve and we'll have the data readout sometime next year, those will be a trigger point for us to discuss that single agent combination dexamethasone, discussions with the regulatory agencies to see if the data would suffice for the regulatory dialogue in the fourth-line plus setting.

從 Iberdomide 的角度來看，正如我們所說，四線成本研究已經在進行中。正如我之前提到的，隨著數據的不斷發展，我們將在明年某個時候讀出數據，這將成為我們討論單藥組合地塞米鬆的觸發點，與監管機構進行討論數據是否足以進行第四線+環境中的監管對話。

And then as the data evolves for the doublets and the triplets in the earlier setting, then we launch the later line trials as well in the earlier settings. Nadim, do you want to add something to that?

然後，隨著早期設置中雙聯體和三聯體的數據不斷變化，我們也會在早期設置中啟動後續的生產線試驗。 Nadim，您想添加一些內容嗎？

Sure. I would just add a couple of points maybe. So thanks, Dane, for your question. The point that Samit had made, our plan had always been to move from the doublet to the triplet, which is, as you know, very important, especially in relapsed and newly diagnosed disease.

當然。也許我只想補充幾點。謝謝丹恩提出的問題。薩米特提出的觀點是，我們的計劃一直是從二聯體轉向三聯體，正如你所知，這非常重要，特別是在復發和新診斷的疾病中。

So having these data at ASH will be an important foundation on how we move the treatment up, from the late-line setting then to the early relapse setting and then ultimately, newly diagnosed setting since you had asked the question about Revlimid and impact in the future. So we have a very clear development plan.

因此，ASH 中的這些數據將成為我們如何升級治療的重要基礎，從晚期治療到早期復發治療，最後是新診斷的治療，因為您提出了有關來那度胺 (Revlimid) 及其對治療的影響的問題。未來。所以我們有一個非常明確的發展計劃。

As Samit says, of course, we have to pass all the clinical gates as we go through but the starting point is the triplet data that we're seeing at ASH now. So we're excited about the opportunity moving forward. Thanks for your question.

正如薩米特所說，當然，我們必須通過所有臨床關卡，但起點是我們現在在 ASH 看到的三聯體數據。因此，我們對未來的機會感到興奮。謝謝你的提問。

The next question comes from David Risinger of Morgan Stanley.

下一個問題來自摩根士丹利的大衛·瑞辛格。

Yes. So I have 2 questions, please. First, could you provide more color on what you need to discuss with the FDA on liso-cel? It seemed to me that discussion should be over by this point.

是的。所以我有兩個問題。首先，您能否提供更多關於您需要與 FDA 就 liso-cel 進行討論的內容？在我看來，討論到此應該結束了。

And a follow-on to that is, are there any issues with the recent manufacturing inspections? Or do you have confidence following those manufacturing inspections?

接下來是，最近的製造檢查是否存在任何問題？或者您對這些製造檢查有信心嗎？

And then the second question is other BCMA ADCs have been associated with ocular tox in multiple myeloma. Do you expect a differentiated profile for your BCMA CC-99712? And when should we expect to see data?

第二個問題是其他 BCMA ADC 與多發性骨髓瘤的眼部毒性有關。您希望 BCMA CC-99712 具有差異化的配置嗎？我們什麼時候應該看到數據？

Thank you for the question. For liso-cel, as we mentioned earlier, as we disclosed in the past, FDA has informed the company that both our plants in Washington as well as the one in Texas need to be inspected. They've been able to inspect our plant in Bothell, Washington, at this time but has not scheduled any inspection of the second plant.

感謝你的提問。對於liso-cel，正如我們之前提到的，正如我們過去所披露的那樣，FDA已通知該公司，我們在華盛頓的工廠以及在德克薩斯州的工廠都需要接受檢查。他們目前已經能夠檢查我們位於華盛頓州博塞爾的工廠，但尚未安排對第二家工廠進行任何檢查。

As you know, as we are doing what they can to ensure that the staff are kept safe in this COVID pandemic. And because of the travel restrictions, we have to obviously honor their desire as to where they go and when they go.

如您所知，我們正在盡一切努力確保員工在新冠疫情期間的安全。由於旅行限制，我們顯然必須尊重他們關於去哪里和何時去的願望。

As we've said in the past, that the conversations with the agencies are going well, and we look forward to seeing the -- hopefully, the approval at some point to be able to bring it to the patients as soon as possible. We'll obviously let you know as soon as we get the decision.

正如我們過去所說，與各機構的對話進展順利，我們期待看到——希望在某個時候獲得批准，以便能夠盡快將其帶給患者。一旦我們做出決定，我們顯然會立即通知您。

We are not going to comment obviously specifically about the dialogue around inspections, et cetera. We're generally very happy with the dialogue that has been happening.

我們不會明確具體評論圍繞檢查等的對話。總的來說，我們對正在進行的對話非常滿意。

On the ADC front, for multiple myeloma, we are in the Phase I. It's early time to comment whether we'll be able to differentiate or not, but we absolutely are aware of the ocular toxicity. And certainly, we'll keep that in mind as we go along. We continue to evaluate the patients for that.

在 ADC 方面，對於多發性骨髓瘤，我們正處於 I 期。現在評論我們是否能夠區分還為時過早，但我們絕對意識到眼部毒性。當然，我們在進行過程中會牢記這一點。我們將繼續對此進行評估。

I think the first data we would see would be sometime late next year because we are still in the dose escalation phase. And so certainly, as soon as the data are mature enough to be presented, we'll be able to bring it to the medical conference and share that with you.

我認為我們將在明年晚些時候看到第一個數據，因為我們仍處於劑量遞增階段。因此，當然，一旦數據足夠成熟可以呈現，我們就能夠將其帶到醫學會議上並與您分享。

Next question comes from Greg Gilbert of Truist.

下一個問題來自 Truist 的格雷格·吉爾伯特。

Giovanni, you've made it very clear that cardiovascular is a core franchise for the company. On Factor XIa, what do you think you have to deliver in terms of clinical profile to enable that asset to add value in what will potentially be a generic environment? And then maybe more strategically, in cardiovascular, it looks like you have at one end of the spectrum, kind of a mass market, Eliquis and Factor XIa approach, and on the other hand, a more specialized approach with MyoKardia. So I assume your strategic vision in cardiovascular spans across that. But curious if you want to be more focused in one end or the other as you consider additional BD and cardiovascular.

喬瓦尼，你已經說得很清楚了，心血管是公司的核心業務。關於因子 XIa，您認為您必須在臨床概況方面提供什麼，才能使該資產在潛在的通用環境中增加價值？然後，也許更具戰略性的是，在心血管領域，看起來你處於一個極端，一種大眾市場，Eliquis 和 Factor XIa 方法，而另一方面，MyoKardia 是一種更專業的方法。因此，我認為您在心血管領域的戰略願景涵蓋了這一點。但很好奇，當您考慮額外的雙相情感障礙和心血管疾病時，您是否想更加專注於一端或另一端。

And then a follow-up for David. How would you describe the LOE step-down for Revlimid in the coming years? And do you think The Street has that right, at least in general in terms of how it's being modeled? We obviously have imperfect information.

然後是大衛的後續行動。您如何描述來那度胺 (Revlimid) 未來幾年 LOE 的降低？您認為《華爾街日報》是否有這種權利，至少在其建模方式方面是這樣？顯然我們的信息不完善。

Thank you, Greg. Let me start, and then maybe I'll ask on -- specifically on cardiovascular and Factor XIa, Samit and Chris to add. And then David will cover your question about the Revlimid LOE.

謝謝你，格雷格。讓我開始吧，然後也許我會問——特別是關於心血管和 XIa 因子的問題，Samit 和 Chris 補充一下。然後 David 將回答您關於 Revlimid LOE 的問題。

So first of all, let me say, yes. To answer your question, cardiovascular is a strategic importance to us, and it has been consistently for the company. And when you look at what we've done with Eliquis, I'm really proud of our ability to develop differentiated assets in cardiovascular, take a very different approach to establishing the value of those assets in the case of Eliquis through real or relevance as an example and maximize the value of the medicine.

首先，我要說，是的。回答你的問題，心血管對我們來說具有戰略重要性，對於公司來說也一直如此。當你看到我們在 Eliquis 上所做的事情時，我真的為我們在心血管領域開發差異化資產的能力感到自豪，在 Eliquis 的情況下，通過實際或相關性，採取一種非常不同的方法來確定這些資產的價值，例如一個例子，最大限度地發揮藥物的價值。

And so whether you look at Eliquis, you look at mavacamten and a Factor XIa inhibitor, we feel really good about our ability to execute in cardiovascular and our commitment to cardiovascular.

因此，無論您考慮 Eliquis、mavacamten 和 XIa 因子抑製劑，我們都對我們在心血管領域的執行能力以及我們對心血管的承諾感到非常滿意。

I think the approaches are different between a broader asset like Eliquis or Factor XIa could be. In those cases, as you know, we made a choice to partner those assets because we want to be working with another company that together, enables us to have a broader reach into a primary care market and support the development of assets that require very large investments in the development of the asset across multiple indications.

我認為 Eliquis 或 Factor XIa 等更廣泛的資產之間的方法可能有所不同。在這些情況下，如您所知，我們選擇與這些資產合作，因為我們希望與另一家公司合作，共同使我們能夠更廣泛地進入初級保健市場，並支持需要大量資產的開發。跨多種適應症的資產開發投資。

I think when you look at mavacamten, it's much more about a precision approach to cardiovascular, which fits really nicely with our R&D strategy. And actually, very consistent with the early pipeline we have in heart failure in cardiovascular. So I don't think it's necessarily, one approach versus the other. But it's really looking at cardiovascular as one of the areas where the unmet need continues to be really high.

我認為當你看到 mavacamten 時，它更多的是關於心血管的精確方法，這非常適合我們的研發策略。事實上，這與我們在心血管心力衰竭方面的早期研究非常一致。所以我認為這不一定是一種方法與另一種方法的對立。但它確實將心血管視為未滿足需求仍然很高的領域之一。

The company has demonstrated ability to execute, which is excellent. And then we take a different approach depending on what an asset needs in order for its value to be maximized, and when we [at best] -- have the best capability. So as we think about it, and actually MyoKardia is a really, really interesting asset because -- an acquisition because the precision approach is really consistent with the way we look at things. Let me just ask Samit, if he wants to add anything on Factor XIa, specifically in differentiation and our development strategy, and then we will move to your question on Revlimid.

該公司表現出了出色的執行能力。然後，我們根據資產需要什麼來實現其價值最大化，以及我們何時（最好）擁有最好的能力，採取不同的方法。因此，當我們思考這一點時，實際上 MyoKardia 是一項非常非常有趣的資產，因為——一次收購，因為精確的方法與我們看待事物的方式非常一致。讓我問 Samit，他是否想在因子 XIa 上添加任何內容，特別是在差異化和我們的開發策略方面，然後我們將轉向您關於 Revlimid 的問題。

Thank you, Giovanni. The one thing that I would also have on mavacamten to remember, patients with obstructive hypertrophic empathy, the ones that are symptomatic, the ones that we are talking about from a treatment perspective, also have arrhythmia , especially atrial fibrillation that they experience. So Eliquis is used there as well, and many cardiologists are very well aware of need of Eliquis. And certainly in the future, when mavacamten potentially might be available, would be very helpful for these patients.

謝謝你，喬瓦尼。關於mavacamten，我還要記住一件事，患有阻塞性肥厚性同理心的患者，那些有症狀的患者，我們從治療角度討論的患者，也有心律失常，尤其是他們經歷的心房顫動。所以 Eliquis 也在那裡使用，許多心髒病專家都非常清楚 Eliquis 的需要。當然，在未來，當 mavacamten 可能上市時，將對這些患者非常有幫助。

Coming back again then on to the anticoagulation and Factor XIa. I think certainly very happy that we are in that stage and the Eliquis, what we have done. The 2 things that are going to be important to remember is, number one, there are still bleeding risk. And patients don't necessarily get treated with full doses of the currently available treatments, and some patients are not even treated because of the bleeding risk.

然後再回到抗凝和 XIa 因子。我認為我們非常高興我們處於這個階段以及 Eliquis，我們所做的一切。需要記住的兩件事是，第一，仍然存在出血風險。而且患者不一定會接受目前可用治療的全劑量治療，有些患者甚至因為出血風險而沒有接受治療。

The second unmet medical need is that patients cannot be treated on top of their background [and late] therapies for indications such as the secondary strokes. And that is a very high unmet medical need and patients who have had a first stroke are at very high risk of experiencing a second stroke, maybe even 50% to 60% probability.

第二個未滿足的醫療需求是，患者無法在其背景[和晚期]治療基礎上接受繼發性中風等適應症的治療。這是一個非常高的未滿足的醫療需求，第一次中風的患者發生第二次中風的風險非常高，甚至可能有 50% 到 60% 的可能性。

And therefore, what we're looking for in the Factor XIa development program as we look at the Phase II studies that are currently ongoing, is the -- is number one, the decrease in the bleeding probabilities. And second is the combined ability, where that background therapy of (inaudible) in the secondary stroke prevention study that is currently ongoing in terms of its enrollment.

因此，當我們查看目前正在進行的 II 期研究時，我們在因子 XIa 開發計劃中尋找的是——第一，出血概率的降低。其次是綜合能力，即目前正在進行的二級中風預防研究中的背景治療（聽不清）。

So those are the important aspects that will make us go into the Phase III development program once the data are available. Let me pass it on to David and to comment further on the Revlimid side.

因此，一旦數據可用，這些都是使我們進入第三階段開發計劃的重要方面。讓我將其轉告 David 並進一步評論 Revlimid 方面。

Yes. Thanks, and Greg, thank you for the question. We made great progress this year on the IP front, both with Revlimid as well as with Eliquis. And as you know, we settled with Dr. Reddy's. We have the settlement with (inaudible), which just to remind you, remember, the macro agreement is a single-digit volume entry in 2022, which grows to about 1/3 by 2025. And we have some other sentiments, which aren't public with Dr. Reddy's and Alvogen.

是的。謝謝，格雷格，謝謝你的提問。今年我們在知識產權方面取得了巨大進展，包括 Revlimid 和 Eliquis。如你所知，我們與雷迪博士達成了和解。我們與（聽不清）達成了和解，這只是為了提醒您，請記住，宏觀協議在 2022 年的交易量為個位數，到 2025 年將增長到約 1/3。我們還有其他一些情緒，與 Dr. Reddy's 和 Alvogen 一起公開。

But as you -- we clearly see it more as a slope, not as a cliff starting in 2022 with full generic entry coming in '26. And at the time we did the acquisition, all I'd say is that we took a more conservative view on Revlimid than the sell-side equity analyst did at that time. So with that said, we still believe Revlimid will add potential significant cash flow for the business over that period from '22 through '25.

但正如您一樣，我們顯然更多地將其視為斜坡，而不是從 2022 年開始的懸崖，完整的通用條目將於 26 年推出。在我們進行收購時，我想說的是，我們對 Revlimid 的看法比當時賣方股票分析師的看法更為保守。話雖如此，我們仍然相信 Revlimid 將為該業務在 22 年至 25 年期間增加潛在的大量現金流。

Yes. Thank you, David. Let me just reiterate. I think specifically to your question, when we look at the period during which over time, the slope of Revlimid will take place between 2022 to -- sorry, 2022 to 2026.

是的。謝謝你，大衛。讓我重申一下。我想具體針對你的問題，當我們考慮隨著時間的推移，Revlimid 的斜率將在 2022 年至 - 對不起，2022 年至 2026 年之間發生。

First of all, I think it is playing out the way we had modeled it to be a slope, and it starts at a point where the overall performance of the brand has been really strong. And our view of IP and the strength of IP has been validated by the IPRs that were not granted and the 2 settlements that David mentioned.

首先，我認為它正在以我們將其建模為斜坡的方式發揮作用，並且它始於該品牌的整體表現非常強勁的點。我們對知識產權和知識產權強度的看法已經被未授予的知識產權和大衛提到的兩項和解所證實。

At the same time, the strength of our business beyond Revlimid has continued to be really, really good. The progress we've made with the pipeline has given us real confidence in our ability as a company to continue to renew the portfolio.

與此同時，除了來那度胺（Revlimid）之外，我們的業務實力仍然非常非常好。我們在管道方面取得的進展使我們對公司繼續更新產品組合的能力充滿信心。

So as I mentioned at the beginning, I feel really good about our ability to continue to perform very strongly as we renew our portfolio during the time in which over time, Revlimid will lose exclusivity. That's what we set out to do from the very beginning. And I think execution so far has been really strong, which makes me confident in our ability to continue to be successful during that time.

因此，正如我在一開始提到的，我對我們在更新產品組合時繼續表現強勁的能力感到非常滿意，隨著時間的推移，來那度胺將失去排他性。這就是我們從一開始就打算做的事情。我認為到目前為止的執行力非常強大，這讓我對我們在此期間繼續取得成功的能力充滿信心。

The next question comes from Matt Phipps of William Blair.

下一個問題來自威廉·布萊爾的馬特·菲普斯。

Congrats on a nice quarter. Wondering if after the positive POETYK study, if you're going to look at moving this asset into a more mild patient setting, similar to the recent Otezla ADVANCE study. And then also a second quick question on the Forbius acquisition. Just wondering if you could compare and contrast maybe moving a TGF-beta monoclonal antibody plus something like Opdivo versus a bispecific molecule like (inaudible) alpha that you do it for the trial kind of combined with the PD-L1 antibody.

恭喜您度過了一個美好的季度。想知道在 POETYK 研究取得積極成果後，您是否打算考慮將這項資產轉移到更溫和的患者環境中，類似於最近的 Otezla ADVANCE 研究。然後是關於 Forbius 收購的第二個快速問題。只是想知道您是否可以將 TGF-β 單克隆抗體加上 Opdivo 等藥物與雙特異性分子（例如（聽不清）α）進行比較和對比，您可以將其與 PD-L1 抗體結合進行試驗。

Thank you for the questions, Matt. First of all, on the TYK2 aspect, so you know that we are very happy with the results from the POETYK 1 study. We also know that there is a broad program already underway where we have the evaluation ongoing in ulcerative colitis and lupus, SLE as well as the inflammatory bowel disease. Mild psoriasis, we certainly have an eye on it. We obviously think about this as we evolve with the data on the psoriasis. We have to look at the overall efficacy and safety profile when the second study also reads out, and that will dictate where we go next in terms of evaluation of deucravacitinib in psoriasis and other indications related to psoriasis.

謝謝你的提問，馬特。首先，在 TYK2 方面，我們對 POETYK 1 研究的結果非常滿意。我們還知道，一項廣泛的計劃已經在進行中，我們正在對潰瘍性結腸炎和狼瘡、系統性紅斑狼瘡以及炎症性腸病進行評估。輕度牛皮癬，我們當然要關注它。隨著銀屑病數據的不斷發展，我們顯然會考慮這一點。當第二項研究也公佈時，我們必須考慮總體療效和安全性，這將決定我們在評估 deucravacitinib 治療銀屑病和與銀屑病相關的其他適應症方面下一步的發展方向。

On the TGF-beta front, we are, of course, aware of the bispecific TGF-beta PD-1 that the competitors have. When we look at TGF data, the specificity of the inhibition caused by this particular antibody is very important. And we certainly will look at the combinations with our own pipeline, not only with nivolumab, but we also have relatlimab, as you know, in development. So we'll be looking at all those combinations as the Phase I study data evolves.

在 TGF-β 方面，我們當然知道競爭對手擁有雙特異性 TGF-β PD-1。當我們查看 TGF 數據時，這種特定抗體引起的抑制的特異性非常重要。我們當然會研究與我們自己的管道的組合，不僅是納武單抗，而且如您所知，我們還有正在開發的 relatlimab。因此，隨著第一階段研究數據的發展，我們將研究所有這些組合。

And we get to see what the dose and the schedule will be for dosing patients with oncologic indications and that will pave the way for the combination strategies looking forward. I think having the ability to give 2 drugs separately will give us more opportunities for combination strategies looking forward.

我們將了解有腫瘤適應症的患者的給藥劑量和時間表，這將為未來的聯合策略鋪平道路。我認為，能夠分別給予兩種藥物將為我們提供更多的機會來製定聯合策略。

The last question today comes from Carter Gould of Barclays.

今天的最後一個問題來自巴克萊銀行的卡特·古爾德。

Great. Congrats on the quarter. I guess, first, a competitor in the TGF space that was perceived to be most closely related to you with also an FC-mutated region discontinued their program recently. In the past, you've been relatively sort of balanced language on the outlook for this program. Any change or updates on how you see there?

偉大的。恭喜本季度。我想，首先，TGF 領域的一個競爭對手被認為與您關係最密切，並且也有 FC 突變區域，最近停止了他們的計劃。過去，您對這個項目的前景一直持相對平衡的語言。您對那裡的看法有什麼變化或更新嗎？

Any commentary on that discontinuation or differentiation that maybe The Street doesn't appreciate between those 2 programs?

對於這兩個項目之間的終止或區別，華爾街可能不欣賞，有什麼評論嗎？

And then maybe coming back to the CELMoDs again. Should we think about the Iberdomide decision sort of running independent to -92480? Or is there going to be a decision to be made at some point next year where you need to sort of pick a winner or can they coexist?

然後也許會再次回到 CELMoD。我們是否應該考慮獨立於 -92480 運行的 Iberdomide 決策？或者明年某個時候你是否會做出決定，需要選出一個獲勝者，或者他們可以共存？

Sure. Thank you, Carter. I think great questions. First of all, on the TULIP side, we certainly have seen the announcement from the competitor from discontinuation of the program on the TULIP side. And we don't know the details and the structure of their molecule, et cetera.

當然。謝謝你，卡特。我認為這是很好的問題。首先，在TULIP方面，我們當然已經看到競爭對手宣布TULIP方面停止該計劃。我們不知道它們分子的細節和結構等等。

But certainly, we have our own molecule, which is in Phase I study. We also have been looking at -- to see where we go with the combination, very early on, to be able to define the path forward.

但當然，我們有自己的分子，目前正處於第一階段研究中。我們也一直在關注——很早就知道我們的合併將走向何方，以便能夠確定前進的道路。

As the data evolves, we'll certainly update you and others in terms of where we go or what the fate of the program will be. But too early to say from our own perspective. The specificity of inert FC portion or an active FC portion, I think still needs to be further investigated before a decisive decision can be made on that side. So more to follow on to in the future.

隨著數據的發展，我們肯定會向您和其他人通報我們的進展或該計劃的命運。但從我們自己的角度來看還為時過早。惰性FC部分或活性FC部分的特異性，我認為在做出決定性決定之前仍需要進一步研究。因此，未來還有更多值得關注的事情。

On the CELMoDs and Iberdomide side. As we said, both of our programs are in development. Iberdomide runs a little bit further because it started earlier. -480 is a very potent molecule. We shared the data of 50-plus percent of overall response rate with -480 plus dexamethasone in the late line setting. Both of those studies are in the development in the full time class setting.

在 CELMoD 和 Iberdomide 方面。正如我們所說，我們的兩個項目都在開發中。伊貝多米德跑得更遠一點，因為它開始得更早。 -480 是一種非常有效的分子。我們分享了在後期線設置中使用 -480 加地塞米鬆的總體緩解率超過 50% 的數據。這兩項研究都在全日制班級環境中進行。

But if you recall, the overall development of [it] in the past, Revlimid and pomalidomide how they were developed in the HER2 Celgene organization, how Revlimid then got set up in the upfront setting and pomalidomide became a preferred molecule for the second third-line patient population.

但如果你還記得它過去的整體發展，來那度胺和泊馬度胺是如何在 HER2 Celgene 組織中開發的，來那度胺是如何在前期設置中建立的，以及泊馬度胺如何成為第二個三分之一的首選分子——線患者群體。

So we have to keep that in mind as we continue to evolve. And we also have the good position that we have a lot of data available from multiple perspective that we can actually investigate to see what is the mechanism, where these drugs will fit the best; what opportunities we may be able to avail in terms of combination strategies with our own pipeline; looking at the platforms that we already have, not only with CELMoDs, but also from the T-cell engager from CAR-T cell therapy as well as the evolving ADC platform.

因此，在我們不斷發展的過程中，我們必須牢記這一點。我們還擁有一個有利的地位，我們從多個角度擁有大量數據，我們可以實際研究這些數據的機制是什麼，這些藥物最適合哪些地方；在與我們自己的管道的組合策略方面，我們可以利用哪些機會；看看我們已經擁有的平台，不僅有 CELMoD，還有來自 CAR-T 細胞療法的 T 細胞接合器以及不斷發展的 ADC 平台。

So those opportunities, because of the T-cells we have in our hand, can certainly be further investigated in a broadest way rather than limiting ourselves to a singular CELMoD. But let me ask Nadim to add anything if he wants to further elaborate on this. Thank you.

因此，由於我們手中有 T 細胞，這些機會當然可以以最廣泛的方式進一步研究，而不是將我們局限於單一的 CELMoD。但是，如果納迪姆想進一步詳細說明這一點，請讓我補充一些內容。謝謝。

Sure. Thanks, Samit, and thanks, Carter, for your question. So I think right now, we're very pleased with the early data we're seeing for both. And as Samit said, we've done the same with Revlimid and Pomalyst in the past. So there are discrete patient segments with very different clinical needs, where you could potentially see the coexistence of both CELMoDs.

當然。謝謝薩米特，也謝謝卡特提出的問題。所以我認為現在我們對兩者的早期數據感到非常滿意。正如 Samit 所說，我們過去對 Revlimid 和 Pomalyst 也做過同樣的事情。因此，不同的患者群體具有截然不同的臨床需求，您可能會看到兩種 CELMoD 共存。

So for example, the maintenance setting, a CELMoD with a better tolerability profile. In a relapse setting with high-risk disease, you could see a more potent CELMoD come through. So I think we're going to continue to look at the data, but we're pleased with how both are progressing.

例如，維護設置是具有更好耐受性的 CELMoD。在高風險疾病復發的情況下，您可能會看到更有效的 CELMoD。因此，我認為我們將繼續關注數據，但我們對兩者的進展感到滿意。

And then as Samit said, one of our key objectives is to come up with this multi-modality combination approach. So you can envisage a CELMoD plus BCMA through multiple lines of therapy as patients progress from newly diagnosed disease to late-stage disease.

正如薩米特所說，我們的主要目標之一是提出這種多模態組合方法。因此，當患者從新診斷的疾病發展到晚期疾病時，您可以設想通過多線治療進行 CELMoD 加 BCMA。

And we've already seen the use of sequential treatment through the current CELMoDs, or even I should say, with Revlimid and Pomalyst. So we do think that the combination of BCMA and CELMoDs, across lines of therapies for different patient segments, could be really important, both clinically and commercially. So thanks for your question.

我們已經看到了通過當前的 CELMoD 序貫治療的使用，或者甚至我應該說，使用 Revlimid 和 Pomalyst。因此，我們確實認為 BCMA 和 CELMoD 的組合，針對不同患者群體的跨系列療法，無論在臨床還是商業上都可能非常重要。謝謝你的提問。

Thank you. Thank you, Nadim, and thanks to all of you for joining our call today. We had a lot to discuss, and I think that speaks to the breadth and depth of our business and importantly, of our pipeline.

謝謝。謝謝你，納迪姆，也感謝大家今天加入我們的電話會議。我們有很多東西要討論，我認為這說明了我們業務的廣度和深度，更重要的是，我們的管道。

So as we discussed, it's been a really active year and a very, very exciting first year for our new company. And I can say with confidence that Bristol-Myers Squibb today is in a really strong position with significant near-term launch opportunities and a substantial pipeline to address unmet needs of patients that will position us very strongly and very well for the future.

正如我們所討論的，對於我們的新公司來說，這是非常活躍的一年，也是非常非常令人興奮的第一年。我可以充滿信心地說，百時美施貴寶今天處於非常有利的地位，擁有重要的近期推出機會和大量管道來滿足患者未滿足的需求，這將使我們在未來處於非常有利和良好的位置。

So thanks again for joining us. And as always, our team will be able to answer further questions you may have. Have a good day. Thanks, everyone.

再次感謝您加入我們。與往常一樣，我們的團隊將能夠回答您可能有的進一步問題。祝你有美好的一天。感謝大家。

Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect.

女士們先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。