施貴寶 (BMY) 2020 Q4 法說會逐字稿

Good day, and welcome to the Bristol-Myers Squibb 2020 Fourth 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 年第四季度業績電話會議。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, Lauren, and good morning, everyone. Thanks for joining us today for our fourth quarter 2020 earnings call. Joining me this morning with prepared remarks as usual are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins; our Chief Financial Officer. And also taking part on today's call are Chris Boerner, our Chief Commercialization Officer; and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development. You'll note that we've posted slides to bms.com that you can use to follow along with for Giovanni and David's remarks.

謝謝勞倫，大家早上好。感謝您今天參加我們的 2020 年第四季度財報電話會議。今天早上，我們的董事會主席兼首席執行官喬瓦尼·卡福里奧 (Giovanni Caforio) 像往常一樣與我一起發表了準備好的講話。和大衛·埃爾金斯；我們的首席財務官。參加今天電話會議的還有我們的首席商業化官 Chris Boerner；以及我們的首席醫療官兼全球藥物開發主管 Samit Hirawat。您會注意到，我們已將幻燈片發佈到 bms.com，您可以使用這些幻燈片來了解 Giovanni 和 David 的言論。

But before we get started, let me read our forward-looking statements. During today's 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.

但在我們開始之前，讓我先閱讀一下我們的前瞻性聲明。在今天的電話會議中，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。

And with that, let me hand over to Giovanni.

接下來，讓我把時間交給喬瓦尼。

Thank you, Tim, and good morning, everyone. I hope you all are staying safe and healthy. I want to open by saying I'm really proud of what we accomplished in 2020. Our teams executed well commercially, advanced our pipeline, kept our integration efforts ahead of schedule and executed important business development activities. We did this while managing through the complexities of the pandemic, keeping our teams safe and our patients at the center of everything we do.

謝謝蒂姆，大家早上好。我希望你們都保持安全和健康。首先我想說，我對我們在 2020 年取得的成就感到非常自豪。我們的團隊在商業上執行得很好，推進了我們的管道，使我們的集成工作提前完成，並執行了重要的業務開發活動。我們在做到這一點的同時，還應對了大流行的複雜性，確保我們團隊的安全，並將患者置於我們所做的一切的中心。

Turning to Slide 4. In Q4, we delivered another strong quarter. Commercial performance was strong, with sales increasing 10% compared to pro forma sales for the same period in the prior year, and we made significant progress to advance our pipeline. Of note, we continued to make progress with our launches, including good momentum for Opdivo + Yervoy in first-line lung, which supports our confidence in a return to growth of Opdivo this year; Reblozyl, which has seen a strong launch with rapid adoption in MDS; Zeposia, which is well positioned as the S1P modulator of choice in multiple sclerosis; and Onureg, which is the only oral option with an overall survival benefit in first-line AML response maintenance. We closed the acquisition of MyoKardia, bringing us mavacamten and strengthening our existing presence in cardiovascular.

轉向幻燈片 4。第四季度，我們又實現了強勁的季度業績。商業業績強勁，銷售額比上年同期預計銷售額增長 10%，我們在推進產品線方面取得了重大進展。值得注意的是，我們的產品上市繼續取得進展，包括 Opdivo + Yervoy 在一線肺治療中的良好勢頭，這支持了我們對 Opdivo 今年恢復增長的信心； Reblozyl 的推出勢頭強勁，並在 MDS 中得到快速採用； Zeposia，它被定位為多發性硬化症的首選 S1P 調節劑； Onureg 是唯一一種在維持一線 AML 反應中具有總體生存獲益的口服選擇。我們完成了對 MyoKardia 的收購，為我們帶來了 mavacamten，並加強了我們在心血管領域的現有業務。

During the quarter, we also continued to advance our pipeline, including regulatory filings and approvals in our I-O, immunology and hematology portfolio, most recently with positive top line results for deucravacitinib in psoriasis. We demonstrated strong financial results, enabling an increased non-GAAP earnings per share outlook for 2021.

本季度，我們還繼續推進我們的產品線，包括 I-O、免疫學和血液學產品組合的監管備案和批准，最近 deucravacitinib 在銀屑病治療中取得了積極的頂線結果。我們展示了強勁的財務業績，從而提高了 2021 年非 GAAP 每股收益的前景。

As you would have just seen, we have entered into a licensing arrangement with The Rockefeller University for the development of a dual antibody combination for the treatment of COVID-19. Though early, we believe this treatment could be differentiated with the potential for low-dose subcutaneous administration. We are pleased to partner with Rockefeller University and leverage our expertise in antibody technology and strength in development, manufacturing and distribution to bring this potential option to patients.

正如您剛才所看到的，我們已與洛克菲勒大學達成許可協議，開髮用於治療 COVID-19 的雙抗體組合。雖然還處於早期階段，但我們相信這種治療方法可以與低劑量皮下注射的潛力區分開來。我們很高興與洛克菲勒大學合作，利用我們在抗體技術方面的專業知識以及開發、製造和分銷方面的實力，為患者帶來這種潛在的選擇。

Moving to Slide 5. Let me put the performance from the quarter and full year 2020 into context. Thanks to excellent execution throughout the year, we have continued to deliver on all value drivers of the Celgene acquisition and laid a strong foundation for future growth of our new company. We are well positioned to accelerate the renewal of our portfolio and support the long-term growth of our business.

轉到幻燈片 5。讓我將 2020 年季度和全年的表現放在背景中。得益於全年出色的執行力，我們繼續實現收購 Celgene 的所有價值驅動因素，並為新公司的未來發展奠定了堅實的基礎。我們處於有利地位，可以加速我們的產品組合更新並支持我們業務的長期增長。

Last month at JPMorgan, I shared why I have confidence in the future of Bristol-Myers Squibb. The integration of Celgene has gone very well. Based on progress last year, we now expect total synergies to be close to $3 billion by the end of '22. We have proven commercial capabilities, which enable us to fully realize the opportunities to grow our in-line portfolio and support strong execution of our launches. The breadth and depth of our late-stage pipeline is reflected in the significant number of milestones delivered last year. Finally, our financial strength makes it possible for us to continue to invest in future growth internally and externally through business development.

上個月，我在摩根大通分享了為什麼我對百時美施貴寶的未來充滿信心。 Celgene 的整合進展順利。根據去年的進展，我們現在預計到 22 年底總協同效應將接近 30 億美元。我們擁有經過驗證的商業能力，這使我們能夠充分認識到發展我們的內嵌產品組合的機會，並支持我們產品發布的強有力執行。去年交付的大量里程碑反映了我們後期研發管線的廣度和深度。最後，我們的財務實力使我們能夠通過業務發展繼續投資於內部和外部的未來增長。

Now turning to Slide 6. Overall, we are in a strong position to unlock the potential of the company we planned to build when we acquired Celgene. We're building a company with a younger, more diversified portfolio of medicines, better positioned in the second half of the decade. Let me remind you when we believe we are heading. We are confident we can more than offset the impact of near-term patent expiries, including Revlimid. We expect to grow our revenue and earnings through 2025, with low to mid-single-digit revenue CAGR for 2025 driven by the significant growth potential of our continuing business, which is comprised of our in-line growth drivers and our launch brands. We see strong momentum for this portfolio, which excludes Revlimid and Pomalyst, with low double-digit revenue CAGR during the same period. Looking out to 2025, we expect the continuing business will represent approximately 90% of the company, with 30% of that revenue from our newly launched products.

現在轉向幻燈片 6。總體而言，我們處於有利地位，可以釋放我們收購 Celgene 時計劃建立的公司的潛力。我們正在建立一家擁有更年輕、更多元化的藥品組合的公司，在本世紀後半葉處於更有利的地位。當我們相信我們正在前進時，讓我提醒您。我們有信心能夠抵消近期專利到期的影響，包括來那度胺 (Revlimid)。我們預計到 2025 年我們的收入和盈利將實現增長，2025 年收入複合年增長率將達到低至中個位數，這得益於我們持續業務的巨大增長潛力，該業務由我們的內線增長驅動因素和我們的推出品牌組成。我們看到該投資組合（不包括 Revlimid 和 Pomalyst）強勁勢頭，同期收入複合年增長率較低。展望 2025 年，我們預計持續業務將占公司的約 90%，其中 30% 的收入來自我們新推出的產品。

Importantly, looking out to the second half of the decade on Slide 7. We have multiple sources of portfolio renewal. Our recently launched products will continue to grow. Most have significant expansion opportunities beyond the launch indication. We have a rich mid- to late-stage pipeline, with assets such as our Factor XIa inhibitor and our multiple myeloma CELMoDs, iberdomide and CC-92480. We will continue to advance our diverse early R&D portfolio and further invest in business development opportunities, just as we have done with MyoKardia. We believe we can achieve this while maintaining very strong profitability, with operating margins expected in the low to mid-40s.

重要的是，在幻燈片 7 上展望本世紀的後半葉。我們有多種投資組合更新來源。我們最近推出的產品將繼續增長。大多數都有超出啟動指示的重大擴展機會。我們擁有豐富的中後期產品線，包括因子 XIa 抑製劑和多發性骨髓瘤 CELMoD、伊伯多胺和 CC-92480 等資產。我們將繼續推進多元化的早期研發組合，並進一步投資於業務發展機會，就像我們對 MyoKardia 所做的那樣。我們相信，我們能夠實現這一目標，同時保持非常強勁的盈利能力，營業利潤率預計在 40 多美元到 40 多美元之間。

Turning to our execution scorecard on Slide 8. At JPMorgan, I outlined several important milestones that would support our success. And as mentioned, we've already delivered on a number of those. Opdivo + CABO was recently approved by the FDA for patients with first-line RCC. This week, we delivered the second positive Phase III for deucravacritinib in plaque psoriasis, supporting the filing of this potential new therapy to help authorities in the near term. Zeposia was filed for the treatment of ulcerative colitis in the U.S., and we look forward to launching that indication later this year.

轉向幻燈片 8 上的執行記分卡。在摩根大通，我概述了支持我們成功的幾個重要里程碑。正如前面提到的，我們已經實現了其中的一些目標。 Opdivo + CABO 最近獲得 FDA 批准用於一線 RCC 患者。本週，我們交付了 deucravacritinib 治療斑塊狀銀屑病的第二個陽性 III 期臨床試驗，支持這種潛在新療法的備案，以在短期內為當局提供幫助。 Zeposia 已在美國申請用於治療潰瘍性結腸炎，我們期待在今年晚些時候推出該適應症。

Moving to Slide 9. As we think about this year, based on the strength of our business and the exciting opportunities ahead, we are increasing our non-GAAP earnings per share guidance for '21. David will provide more details on the financials, but let me offer some perspective on key areas of focus in '21. Commercially, we expect revenue growth across key businesses, driven in large part by the continued execution of our recent launches, Opdivo's return to growth and Eliquis.

轉向幻燈片 9。當我們考慮今年時，基於我們的業務實力和未來令人興奮的機會，我們正在提高 21 年的非 GAAP 每股收益指導。 David 將提供有關財務狀況的更多詳細信息，但讓我對 21 年重點關注領域提供一些看法。在商業方面，我們預計關鍵業務的收入將增長，這在很大程度上得益於我們最近推出的產品的持續執行、Opdivo 的恢復增長和 Eliquis。

We will continue to advance our pipeline and have important milestones ahead this year, such as filing mavacamten, Phase II data for Factor XIa, proof-of-concept data for deucravacritinib in ulcerative colitis and initial data for iberdomide in refractory multiple myeloma. We will maintain a balanced approach to capital allocation. Disciplined business development is a top priority and provides an opportunity to further invest in future growth. David will provide more color on our consistent approach to capital allocation in a few minutes.

我們將繼續推進我們的產品線，並在今年取得重要的里程碑，例如提交 mavacamten、因子 XIa 的 II 期數據、deucravacritinib 治療潰瘍性結腸炎的概念驗證數據以及 iberdomide 治療難治性多發性骨髓瘤的初始數據。我們將保持均衡的資本配置。嚴格的業務發展是重中之重，並為進一步投資未來增長提供了機會。幾分鐘後，大衛將就我們一貫的資本配置方法提供更多信息。

This year, we also anticipate the U.S. policy environment will continue to evolve, and I'm confident the diversification of our portfolio will help us navigate potential changes. We agree that patient affordability needs to be improved, and we are supportive of policies that can address this issue. We look forward to working with the new administration and congressional leaders to foster an environment that supports innovation and enhances patient access to medicines.

今年，我們還預計美國的政策環境將繼續發展，我相信我們投資組合的多元化將幫助我們應對潛在的變化。我們同意患者的負擔能力需要提高，並且我們支持可以解決這個問題的政策。我們期待與新政府和國會領導人合作，營造一個支持創新和改善患者獲得藥物的環境。

To close, I am encouraged by the strength and momentum across the company. Across our 4 key therapeutic areas of hematology, oncology, cardiovascular and immunology, we have leading in-line medicines, significant short-term launch opportunities and a rich pipeline. Our diversified portfolio and leading position in each business allows us to be less dependent on any 1 product or business.

最後，我對整個公司的實力和勢頭感到鼓舞。在血液學、腫瘤學、心血管和免疫學這 4 個關鍵治療領域，我們擁有領先的在線藥物、重要的短期上市機會和豐富的產品線。我們多元化的產品組合和在每項業務中的領先地位使我們能夠減少對任何一種產品或業務的依賴。

I'm also immensely proud of our employees. Their talent is second to none and their commitment is inspiring. I feel very good about the future of Bristol-Myers Squibb and the potential that lies before us. I will now hand it over to David to walk you through the financials. David?

我也為我們的員工感到非常自豪。他們的才華是首屈一指的，他們的承諾令人鼓舞。我對百時美施貴寶的未來以及我們面前的潛力感到非常滿意。現在我將把它交給大衛來引導您了解財務狀況。大衛？

Thank you, Giovanni, and hello, everyone, and thanks again for joining our call today. If you turn to Slide 11, I'd like to discuss our robust top line performance for the quarter. Our teams continued to operate well in a virtual environment, delivering very strong quarterly and full year results. For the fourth quarter, revenues grew 10% on a pro forma basis versus prior year, reflecting strong execution across the world. During the quarter, we also saw approximately $250 million of favorable inventory build versus the third quarter, primarily driven by Eliquis and Revlimid as well as a 2% favorable impact from foreign exchange. Full year revenues were equally strong and reflect a pro forma growth of 7%.

謝謝喬瓦尼，大家好，再次感謝您今天加入我們的電話會議。如果您翻到幻燈片 11，我想討論一下我們本季度強勁的營收表現。我們的團隊繼續在虛擬環境中良好運營，交付了非常強勁的季度和全年業績。第四季度的收入預計比去年同期增長 10%，反映出全球範圍內的強勁執行力。在本季度，我們還看到與第三季度相比，庫存增加了約 2.5 億美元，這主要是由 Eliquis 和 Revlimid 以及外匯帶來的 2% 的有利影響推動的。全年收入同樣強勁，預計增長 7%。

I'll now provide additional color on the performance of our key brands and new launches. Now starting with Eliquis on Slide 12. Global sales continued to perform very well, growing double digit for both the fourth quarter and the full year. In the U.S., fourth quarter sales increased 6% versus prior year, driven by robust 17% TRx growth and an inventory build partially offset by expected higher gross to net impact from the coverage gap. Inventory build versus prior quarter was approximately $100 million. Though we saw total new scripts for oral anticoagulants declining during last year due to COVID, we are starting to see naive volumes return to pre COVID levels.

我現在將提供有關我們主要品牌和新產品的表現的更多信息。現在從幻燈片 12 上的 Eliquis 開始。全球銷售額繼續表現出色，第四季度和全年均實現兩位數增長。在美國，第四季度銷售額與去年同期相比增長了 6%，這得益於 17% 的強勁 TRx 增長，以及庫存增加，部分抵消了覆蓋範圍缺口帶來的毛淨比預期上升的影響。與上一季度相比，庫存增加約為 1 億美元。儘管我們看到去年由於新冠疫情，口服抗凝劑的新處方總量有所下降，但我們開始看到初始用量恢復到新冠疫情前的水平。

Internationally, sales remained strong with revenue of approximately $1 billion, growing 19% versus prior year. Eliquis continues to be the #1 NOAC in multiple key markets internationally, including Germany, France and the U.K. Both in the U.S. and internationally, we believe that the growth outlook for Eliquis remains strong as we continue to grow the oral anticoagulant class as well as increasing our share within the class.

在國際上，銷售依然強勁，收入約為 10 億美元，比上年增長 19%。 Eliquis 仍然是國際多個主要市場（包括德國、法國和英國）排名第一的 NOAC。無論是在美國還是在國際上，我們相信，隨著我們繼續發展口服抗凝劑類別和藥物，Eliquis 的增長前景依然強勁。增加我們在班級中的份額。

Turning to Slide 13. Global sales of Opdivo grew 2% in the fourth quarter versus prior year, primarily driven by strong growth in international markets. In the U.S., the teams continued to execute well, largely through remote engagement. During the fourth quarter, we saw an expected unwind of favorable inventory we discussed last quarter. Importantly, our first-line lung cancer continues to go very well with our share now in the low double-digit range. This is visible by the strong 20% sales growth of Yervoy in the quarter versus prior year.

轉向幻燈片 13。第四季度 Opdivo 的全球銷售額與去年同期相比增長了 2%，這主要是由國際市場的強勁增長推動的。在美國，團隊主要通過遠程參與繼續表現良好。在第四季度，我們預計上季度討論的有利庫存將會減少。重要的是，我們的一線肺癌繼續進展順利，目前我們的份額處於較低的兩位數範圍內。從 Yervoy 本季度銷售額較去年同期強勁增長 20% 可以看出這一點。

We continue to work through the pressure of our second-line indication, which is stabilizing and now starting being balanced out by the momentum we are building in first-line lung. We remain very confident in the return to growth for Opdivo in the U.S. this year. We expect continued growth in first-line lung, combined with launches and additional indications, including first-line renal with the recent approval of Opdivo + CABO and the opportunity to be the first I-O agent in first-line gastric as well as several new adjuvant launches.

我們繼續努力克服二線適應症的壓力，該壓力正在穩定，現在開始被我們在一線肺部建立的勢頭所平衡。我們對 Opdivo 今年在美國恢復增長仍然充滿信心。我們預計肺一線業務將持續增長，同時推出新產品和其他適應症，包括最近批准 Opdivo + CABO 的一線腎臟業務，以及有機會成為一線胃病的第一個 I-O 藥物以及幾種新的佐劑發射。

Internationally, we continue to see strong commercial execution, with growth primarily driven by first-line melanoma and RCC as we continue to secure reimbursement around the world. We are pleased with the recent Japanese approvals and the launch in first-line lung with a broad label in all comers as well as the EU approval of 9LA, and will we be working on securing reimbursements in various countries throughout 2021.

在國際上，我們繼續看到強勁的商業執行力，隨著我們繼續在世界各地獲得報銷，增長主要由一線黑色素瘤和腎細胞癌推動。我們對最近日本的批准、在所有領域廣泛標籤的一線肺部產品的推出以及歐盟對 9LA 的批准感到高興，我們將努力確保 2021 年在各個國家獲得報銷。

Now moving to our in-line multiple myeloma portfolio on Slide 14. Revlimid and Pomalyst continue to perform very well with strong double-digit quarterly growth on a pro forma basis. Globally, Revlimid grew 18%, primarily driven by continued increase in treatment duration. In the U.S., fourth quarter revenues increased 15%, primarily driven by solid demand and inventory build compared to prior year. The inventory build versus prior quarter was approximately $100 million, and we expect this inventory build to reverse in the first quarter.

現在轉向幻燈片 14 上的多發性骨髓瘤產品組合。Revlimid 和 Pomalyst 繼續表現出色，預計季度增長率為兩位數。在全球範圍內，來那度胺 (Revlimid) 增長了 18%，主要是由於治療持續時間的持續增加。在美國，與去年相比，第四季度收入增長了 15%，這主要是由強勁的需求和庫存增加推動的。與上一季度相比，庫存增加約為 1 億美元，我們預計這一庫存增加將在第一季度出現逆轉。

Outside the U.S., revenues were strong with growth of 24% in the fourth quarter versus prior year due to growth in ATRIPLA combination, which include new reimbursement for RVD in several countries. We should note that this strong revenue growth included an earlier-than-expected tender of approximately $80 million. Pomalyst global pro forma revenues continue to reflect significant growth, up 21%. In the U.S., pro forma revenues increased 18% and internationally up 27%, driven by increased usage in earlier lines and longer treatment durations. As we look through the first quarter of 2021, our MM portfolio, in addition to the inventory build in the U.S., I would like to remind you of the typical seasonality of Revlimid and Pomalyst experienced due to patients entering the Medicare coverage gap earlier in the year.

在美國以外地區，由於 ATRIPLA 組合的增長（其中包括多個國家的新 RVD 報銷），第四季度收入較上年同期增長 24%，表現強勁。我們應該注意到，這種強勁的收入增長包括提前於預期的約 8000 萬美元的招標。 Pomalyst 全球預計收入繼續顯著增長，增長 21%。在美國，預計收入增長了 18%，在國際上增長了 27%，這主要得益於早期治療線使用量的增加和治療持續時間的延長。當我們回顧 2021 年第一季度時，我們的 MM 投資組合，除了美國的庫存建設之外，我想提醒您，Revlimid 和 Pomalyst 由於患者較早進入醫療保險覆蓋缺口而經歷了典型的季節性。年。

Now moving on to our recent launches on Slide 15. Our new launches contributed just over $300 million in 2020. Reblozyl is off to a great start with global revenues in the year of $274 million. In the U.S., we experienced significant pent-up demand from the MDS launch in Q2 and Q3. And during the fourth quarter, we began to see expected evolution from the original bolus to true underlying demand. We continue to expect growth through new patient starts early in their treatment journey. Internationally, initial launches in Germany and Austria are going very well. We continue our launches in various markets globally over the course of 2021 as we receive reimbursement.

現在轉到幻燈片 15 上我們最近推出的產品。我們的新產品在 2020 年貢獻了 3 億多美元。Reblozyl 開局良好，今年的全球收入為 2.74 億美元。在美國，我們在第二季度和第三季度經歷了 MDS 推出帶來的大量被壓抑的需求。在第四季度，我們開始看到預期的從最初的推注演變為真正的潛在需求。我們繼續期望新患者在治療過程的早期就開始增長。在國際上，德國和奧地利的首次推出進展順利。在收到補償後，我們將在 2021 年繼續在全球各個市場推出產品。

Now turning to Zeposia. Strong commercial access has been secured with greater than 90% of U.S. commercial lives covered. We remain focused on driving demand and establishing Zeposia as the leading S1P modulator in multiple sclerosis. Outside U.S., we have now launched in Germany, Switzerland, Canada, the Netherlands and Norway. And we'll continue to secure reimbursement in other markets throughout the year. In addition to our MS launch, we now have a PDUFA date for Zeposia in UC in May and look forward to building momentum of this differentiated medicine. An MAA has been validated in Europe and we will work with European health authorities to bring this medicine to patients as soon as possible.

現在轉向澤波西婭。商業准入保障有力，覆蓋美國90%以上的商業生活。我們仍然專注於推動需求並將 Zeposia 打造為多發性硬化症領域領先的 S1P 調節劑。在美國之外，我們現已在德國、瑞士、加拿大、荷蘭和挪威推出。我們將繼續確保全年其他市場的報銷。除了 MS 的推出外，我們現在還確定了 5 月份 Zeposia 在 UC 的 PDUFA 日期，並期待為這種差異化藥物建立動力。 MAA 已在歐洲得到驗證，我們將與歐洲衛生當局合作，盡快將這種藥物帶給患者。

Moving on to Onureg. Initial feedback from physicians has been very positive in establishing Onureg as the first and only oral treatment to demonstrate an overall survival benefit for first-line AML maintenance patients. With the data now published in the New England Journal of Medicine, we are focusing on educating physicians on this new maintenance therapy for patients. The MAA remains under review in EU with approval expected this year.

繼續前往奧努雷格。醫生的初步反饋非常積極，將 Onureg 確定為第一個也是唯一一個口服治療藥物，以證明一線 AML 維持治療患者的總體生存獲益。根據目前發表在《新英格蘭醫學雜誌》上的數據，我們致力於向醫生提供關於這種新的患者維持療法的教育。 MAA 仍在歐盟接受審查，預計今年獲得批准。

Now moving to our balance sheet and capital allocation on Slide 16. You'll see we continue to generate a significant amount of cash flow from operations of approximately $3.4 billion in the fourth quarter. We ended the quarter in a strong liquidity position with approximately $16 billion in cash and marketable securities. Our capital allocation priorities are unchanged. Business development remains a top priority. We're committed to reducing our debt and returning capital to shareholders.

現在轉到幻燈片 16 上的資產負債表和資本配置。您會看到我們在第四季度繼續從運營中產生大量現金流，約為 34 億美元。本季度結束時，我們的流動性狀況良好，擁有約 160 億美元的現金和有價證券。我們的資本配置優先順序沒有改變。業務發展仍然是重中之重。我們致力於減少債務並向股東返還資本。

With respect to business development, we plan to focus on strengthening our pipeline on midsized bolt-on deals that further strengthen the company into the second half of the decade. We will remain disciplined with respective deals that we execute and consistent with our criteria of being strategically aligned, scientifically sound and financially attractive.

在業務發展方面，我們計劃重點加強中型補充交易的渠道，以進一步增強公司的實力，進入本世紀下半葉。我們將繼續嚴格執行我們執行的各項交易，並遵守我們的戰略一致、科學合理和財務有吸引力的標準。

As it relates to reducing debt, we will continue to be focused on this, further strengthening our ability to invest for growth. This morning, we announced a debt reduction transaction of up to $4 billion. Based upon the bonds we are targeting, we still expect to see our leverage ratio reduce by 1.5x debt-to-EBITDA in '24. Importantly, we are committed to a strong investment-grade credit rating, which is apparent through our willingness to use excess cash to proactively accelerate debt reduction.

由於這與減少債務有關，我們將繼續關注這一點，進一步加強我們投資促進增長的能力。今天早上，我們宣布了一項高達 40 億美元的債務減免交易。根據我們的目標債券，我們仍然預計 2024 年我們的槓桿率將減少 1.5 倍債務與 EBITDA。重要的是，我們致力於獲得強大的投資級信用評級，這一點從我們願意使用多餘現金積極加速債務削減就可見一斑。

Lastly, we are committed to returning capital to shareholders through continued dividend growth and share repurchases. We have increased our dividend for the 12th consecutive year and recently increased our share repurchase authorization, with plans to execute a total of $3 billion to $4 billion in share repurchases by the end of this year.

最後，我們致力於通過持續的股息增長和股票回購向股東返還資本。我們已連續第 12 年增加股息，最近還增加了股票回購授權，計劃在今年年底前執行總額為 30 億至 40 億美元的股票回購。

Now let's turn to our guidance for 2021 on Slide 17. Let me start by giving a quick update on our synergies. As Giovanni mentioned, the integration has gone very well, and we increased our total expected synergies to approximately $3 billion by the end of '22. We achieved about $1.4 billion in 2020 and expect the remaining synergy capture to be split evenly through this year and in '22. With that in mind and considering the momentum we saw in the business in 2020, we have increased our non-GAAP diluted EPS guidance for 2021.

現在讓我們轉向幻燈片 17 上的 2021 年指導。首先讓我快速介紹一下我們的協同效應。正如 Giovanni 提到的，整合進展順利，到 22 年底，我們將預期協同效應總額增加到約 30 億美元。我們在 2020 年實現了約 14 億美元的目標，預計剩餘的協同效應將在今年和 22 年平均分配。考慮到這一點並考慮到我們在 2020 年業務中看到的勢頭，我們提高了 2021 年非 GAAP 攤薄後每股收益指引。

Now touching on our non-GAAP expectation at constant exchange rates. We expect high single-digit revenue growth over 2020 based on the strength of our in-line products and the launches we are executing. We expect to sustain a high enterprise gross margin of approximately 80.5%.

現在談談我們對固定匯率的非公認會計準則預期。基於我們的系列產品的實力和我們正在執行的產品發布，我們預計 2020 年收入將實現高個位數增長。我們預計企業毛利率將維持在80.5%左右的較高水平。

Now I want to take a moment to touch on MS&A. In 2020, we had the opportunity to make a number of incremental and accelerated investments to support our prioritized brands and product launches. Also, with COVID recovery and higher expenses due to MyoKardia are reflected. For 2021, we expect MS&A to increase in the low single digit as we invest in our launches and include the full year spend for MyoKardia. We expect mid-single-digit increase in R&D as we invest behind a robust pipeline, COVID recovery plans in preclinical and clinical studies and incorporate spend of MyoKardia. We expect our tax rate to remain about 16%. And finally, based on the strength and the momentum in the business, we are now increasing our non-GAAP 2021 diluted EPS to $7.35 to $7.55.

現在我想花點時間談談 MS&A。 2020 年，我們有機會進行多項增量和加速投資，以支持我們的優先品牌和產品發布。此外，隨著新冠病毒的恢復，以及因心肌病導致的更高費用也得到了體現。 2021 年，我們預計 MS&A 將以低個位數增長，因為我們投資於我們的產品發布，並包括 MyoKardia 的全年支出。我們預計研發將實現中個位數增長，因為我們投資了強大的產品線、臨床前和臨床研究中的新冠病毒恢復計劃以及 MyoKardia 的支出。我們預計稅率將保持在 16% 左右。最後，根據業務的實力和勢頭，我們現在將非 GAAP 2021 年攤薄後每股收益提高至 7.35 美元至 7.55 美元。

I would also like to provide some color on OI&E and share count. It's likely we'll see (inaudible) income and net interest expense to roughly offset each other in 2021, resulting in net neutral OI&E. Regarding our share count, we ended 2020 with approximately 2.3 billion shares outstanding, which will decrease based upon the $3 billion to $4 billion repurchase activity we're planning in the year.

我還想提供一些有關 OI&E 和股票數量的信息。我們很可能會看到（聽不清）收入和淨利息支出在 2021 年大致相互抵消，從而產生淨中性 OI&E。就我們的股票數量而言，截至 2020 年，我們已發行的股票數量約為 23 億股，這一數字將根據我們今年計劃的 30 億至 40 億美元的回購活動而減少。

Now before we move on to Q&A session, I want to thank our teams around the world for delivering such outstanding results in 2020. These results demonstrate the resiliency of our portfolio and position us well for strong growth in 2021 and into the future.

現在，在我們進入問答環節之前，我要感謝我們世界各地的團隊在 2020 年取得瞭如此出色的業績。這些結果證明了我們產品組合的彈性，並使我們為 2021 年和未來的強勁增長做好了準備。

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。

Thanks very much, David. Lauren, can we go for our first question, please?

非常感謝，大衛。勞倫，我們可以回答第一個問題嗎？

(Operator Instructions) Our first question comes from Geoff Meacham with Bank of America.

（操作員說明）我們的第一個問題來自美國銀行的 Geoff Meacham。

Just have 2 quick ones. For Chris, when you look at the new launches on Slide 15, obviously, these are a big part of the LOE offset over time. So the question is, where do you see the tipping point in demand for these 3 products? And how should we think about initial adoption for liso-cel and ide-cel later this year?

只要有2個快速的。對於 Chris 來說，當您查看幻燈片 15 上的新發佈時，顯然，這些是隨著時間的推移 LOE 抵消的重要組成部分。那麼問題是，您認為這 3 種產品的需求臨界點在哪裡？我們應該如何考慮今年晚些時候首次採用 liso-cel 和 ide-cel？

And then development question for deucravacritinib. Just want to get your thoughts on safety and tolerability. Not having a black box will obviously be a big commercial driver, but it's possible that recent safety data for Xeljanz and a somewhat related mechanism could directly impact you guys. I want to get your thoughts on that.

然後是 deucravacritinib 的開發問題。只是想了解您對安全性和耐受性的想法。沒有黑匣子顯然會成為一個巨大的商業驅動力，但 Xeljanz 的最新安全數據和某種相關機制可能會直接影響你們。我想听聽你對此的想法。

Sure. Let me start with the question on the tipping point and then also your question with respect to liso-cel. And maybe I'll start with the question on liso-cel and how we're thinking about the launch there. We're obviously very excited about the opportunity to launch liso-cel in DLBCL. We expect that imminently. We are obviously going to be very much focused on ensuring at launch that sites are activated very quickly, that we're able to get patients efficiently moved on to therapy.

當然。讓我從關於臨界點的問題開始，然後是關於 liso-cel 的問題。也許我會從關於 liso-cel 的問題以及我們如何考慮在那裡推出的問題開始。顯然，我們對有機會在 DLBCL 中推出 liso-cel 感到非常興奮。我們預計這一點即將到來。顯然，我們將非常專注於確保在啟動時站點能夠非常快速地激活，以便我們能夠有效地讓患者繼續接受治療。

And then as we stated repeatedly, really, the tipping point with (inaudible) to is going to be our ability to continue to expand the CAR-T market by driving referrals and expanding the site footprint and then ultimately being able to leverage what we believe to be a differentiated product profile in order to drive brand share. And so that's going to be very important.

然後，正如我們反復指出的那樣，（聽不清）的轉折點將是我們通過推動推薦和擴大網站足跡來繼續擴大 CAR-T 市場的能力，然後最終能夠利用我們所相信的東西形成差異化的產品形象，以提高品牌份額。所以這將非常重要。

And a similar story will be for ide-cel, where obviously, we have a very strong position in multiple myeloma to leverage. With respect to staying in hematology of the 3 products that were on the slide, Reblozyl. Obviously, Reblozyl is off to a very good start. We're very pleased with the launch so far. The execution for this probably has gone very well, and we continue to believe Reblozyl is going to play a very important role in both MDS and beta thalassemia. As we look at where the launch is at this point, we think thus far, we've had very good demand. Some of that demand, frankly, has been pent-up. And as we get into the first quarter and certainly into this year, we think we'll be tapping into the true underlying demand.

ide-cel 的情況也類似，顯然，我們在多發性骨髓瘤領域擁有非常強大的地位可以利用。關於幻燈片上 3 種產品的血液學方面，Reblozyl。顯然，Reblozyl 有了一個非常好的開始。到目前為止，我們對發布感到非常滿意。這項工作的執行可能進展順利，我們仍然相信 Reblozyl 將在 MDS 和 β 地中海貧血中發揮非常重要的作用。當我們看看目前的發布情況時，我們認為到目前為止，我們的需求非常好。坦率地說，其中一些需求已被壓抑。當我們進入第一季度，當然還有今年，我們認為我們將挖掘真正的潛在需求。

But we continue to see real opportunity to grow this brand both in its labeled indication as well as potentially to expand into the first-line ESA-naive with the COMMANDS studies and ultimately potentially into (inaudible).

但我們繼續看到真正的機會來發展這個品牌，無論是在其標籤適應症方面，還是通過命令研究擴展到一線 ESA 新手，並最終可能進入（聽不清）。

And then for Onureg, Onureg is obviously off to a very good start. As David mentioned, there remains a very high unmet need for patients in first-line AML who've achieved a CR post-intensive chemo but aren't candidates for stem cell. We believe that really, the opportunity here is going to be to continue to drive the benefit that we see from an overall survival standpoint with Onureg.

然後對於奧努雷格來說，奧努雷格顯然有了一個非常好的開始。正如 David 提到的，一線 AML 患者在強化化療後已達到 CR，但不適合幹細胞治療，但其需求仍未得到滿足。我們相信，實際上，這裡的機會將是繼續推動我們從 Onureg 的整體生存角度看到的利益。

But importantly, this is a market where there is no established treatment approach in AML maintenance. So what we're going to have to do is continue to build that market and convince physicians that it's a new paradigm to treat these patients and that there's a real urgency to treat them.

但重要的是，這個市場在 AML 維持方面尚無既定的治療方法。因此，我們要做的就是繼續建立這個市場，並讓醫生相信這是治療這些患者的新範例，並且治療他們確實緊迫。

And then finally, to pick up on the question on Zeposia, we are very pleased with what we have seen with the opportunity for Zeposia, not only in MS, but particularly in IBD. The MS launch, we think, is going well. In spite of the situation with COVID, we've seen good uptake from physicians in terms of willingness to prescribe. Importantly, the percentage of physicians who now believe that Zeposia is the best S1P is very much on track with what we had hoped for. And given the data that we saw with True North, we think there's considerable opportunity for us to drive business there as well. So very excited about the opportunity with Zeposia. Maybe I'll turn it over to Samit.

最後，關於 Zeposia 的問題，我們對 Zeposia 的機會感到非常高興，不僅在 MS 領域，而且特別是在 IBD 領域。我們認為 MS 的發布進展順利。儘管存在新冠疫情的情況，我們還是看到醫生開藥的意願良好。重要的是，現在認為 Zeposia 是最好的 S1P 的醫生比例非常符合我們的預期。鑑於我們在 True North 看到的數據，我們認為我們也有相當大的機會推動那裡的業務。對於有機會與 Zeposia 合作，我感到非常興奮。也許我會把它交給薩米特。

Thanks, Chris, and thanks, Geoff, for the question (inaudible) And let me just start first by saying that for (inaudible) deucravacitinib, this is not a JAK inhibitor. And the reason I'd say that is because of the specificity and selectivity in terms of targeting TYK2, downstream inhibition of IL-12/23 and intracranial alpha, which leads to a profile that is differentiated. We do not see the signals of lab abnormalities that are generally associated with JAK inhibitors. We do not see the signals for VTEs that are generally associated with JAK inhibitors.

謝謝 Chris，也謝謝 Geoff 提出這個問題（聽不清）首先讓我說，對於（聽不清）deucravacitinib，它不是 JAK 抑製劑。我這麼說的原因是因為針對 TYK2、IL-12/23 下游抑制和顱內 α 的特異性和選擇性，這導致了差異化的概況。我們沒有看到通常與 JAK 抑製劑相關的實驗室異常信號。我們沒有看到通常與 JAK 抑製劑相關的 VTE 信號。

What we have are 2 very well-conducted Phase III trials showing remarkable efficacy. We are very pleased with the data that we've seen, meeting the primary and secondary endpoints. And we are now looking forward to the data evolving, as Giovanni mentioned on one of his slides, in the next generation of trials that are ongoing in IBD, SLE and beyond. So we are looking forward to the readout of those trials and very pleased with where we stand.

我們擁有兩項進行得非常順利的 III 期試驗，顯示出顯著的療效。我們對所看到的數據非常滿意，滿足主要和次要終點。正如 Giovanni 在他的一張幻燈片中提到的那樣，我們現在期待著 IBD、SLE 等正在進行的下一代試驗中的數據不斷發展。因此，我們期待著這些試驗的結果，並對我們的現狀感到非常滿意。

Our next question comes from Terence Flynn with Goldman Sachs.

我們的下一個問題來自高盛的特倫斯·弗林。

Just maybe 2 parts. First, on Opdivo, Chris, was just wondering if you can help us think about the cadence of contribution from some of the new approvals, CheckMate 9ER. And then maybe on the adjuvant side, when we could start seeing some pull-through there? Is this more the growth going to be weighted to the second half of the year? And then on Factor XIa, Samit, maybe you could just opine here on kind of what you're hoping to see on the profile from the initial Phase II trial later this year?

也許只有 2 部分。首先，關於 Opdivo，Chris 只是想知道您是否可以幫助我們考慮一些新批准的 CheckMate 9ER 的貢獻節奏。然後也許在輔助方面，我們什麼時候可以開始看到一些突破？這是否會更多地考慮下半年的增長？然後，關於 XIa 因子，Samit，也許您可以在這裡發表一下您希望在今年晚些時候的初始 II 期試驗的概況中看到的內容？

Let me start, Terence, and then I'll turn it over to Samit. So yes, so we're excited for the outlook for Opdivo. As was mentioned earlier in the call, we do see continued confidence that Opdivo is going to return to growth in 2021 and contribute meaningfully as part of the I-O franchise to company growth beyond that.

讓我開始吧，特倫斯，然後我會把它交給薩米特。所以，是的，我們對 Opdivo 的前景感到興奮。正如之前在電話會議中提到的，我們確實相信 Opdivo 將在 2021 年恢復增長，並作為 I-O 特許經營權的一部分為公司的增長做出有意義的貢獻。

What I would say to answer your question on 9ER is, first of all, 9ER needs to be put within the context of, first of all, a very stable business that we're starting to see in the U.S., a strong business as you saw in the numbers in Q4 ex U.S. And then as David mentioned, we've seen good uptake in the first-line lung launch in the U.S., and it's still very early days outside of the U.S.

要回答您關於 9ER 的問題，我想說的是，首先，9ER 需要置於這樣的背景下：首先，我們開始在美國看到一個非常穩定的業務，一個像您一樣強大的業務。從第四季度（美國除外）的數據中可以看出，正如 David 提到的，我們在美國看到一線肺部產品的推出情況良好，而在美國以外的地區仍處於早期階段。

We do see that there is a nice opportunity with 9ER in first-line renal. Again, as we talked about, we've got an established footprint with Opdivo + Yervoy there, and we think that by giving us the opportunity to combine with what we believe to be a best-in-class TKI with CABO, there's opportunity to grow that business, particularly as we think about getting into the favorable patient population. Still very early days since we were just approved on the 22nd.

我們確實看到 9ER 在一線腎臟治療中有一個很好的機會。再次，正如我們所討論的，我們已經在那裡建立了 Opdivo + Yervoy 的足跡，我們認為，通過給我們機會與我們認為是一流的 TKI 與 CABO 相結合，我們就有機會發展這項業務，特別是當我們考慮進入有利的患者群體時。距離我們 22 日剛剛獲得批准還為時過早。

And then with respect to the additional opportunities, as you know, we have [Opdivo's] launch opportunities with gastric cancer in the first-line metastatic space as well as in the adjuvant space as well as with adjuvant bladder. We do think that those are going to be more indexed to the latter half of this year and then as we get into '22 in terms of their contribution to growth. Maybe with that, I'll turn it over to Samit.

然後，關於額外的機會，如您所知，我們有[Opdivo]在一線轉移性空間、輔助空間以及輔助膀胱中針對胃癌的上市機會。我們確實認為，這些將更多地反映在今年下半年，然後當我們進入 22 世紀時，就它們對增長的貢獻而言。也許這樣，我會把它交給薩米特。

Thanks, Chris, and thanks, Terence, for the question. For Factor XIa, we expect to have the data from the first of the 2 proof-of-concept studies that are ongoing, the first one being in the total knee replacement trial population. And there, we are doing the dose-ranging study and we are evaluating safety and efficacy of the oral factor XIa single agent versus enoxaparin administrated subcutaneously for these subjects.

謝謝克里斯，也謝謝特倫斯提出的問題。對於因子 XIa，我們期望獲得正在進行的兩項概念驗證研究中第一項的數據，第一項是在全膝關節置換試驗人群中。我們正在進行劑量範圍研究，並評估口服因子 XIa 單藥與皮下注射依諾肝素對這些受試者的安全性和有效性。

So what we are trying to see is the profile that emerges from a bleeding perspective, whether we can have a similar or better efficacy with less bleeding. More importantly then, there will be the second study next year looking at a combination to the background therapy of the anti-platelet agents where, again, it is very important to note that, that profile, what impact it will have on bleeding? And if we are able to combine, then it opens up additional indications that we can pursue going forward. So those are the 2 things that we'll be watching out for defining the dose, looking at the safety and, of course, efficacy will also be a point of review.

因此，我們想要看到的是從出血的角度來看，我們是否可以在出血較少的情況下獲得類似或更好的療效。更重要的是，明年將進行第二項研究，著眼於抗血小板藥物背景治療的組合，再次強調，這一點非常重要，它會對出血產生什麼影響？如果我們能夠合併，那麼這就為我們未來的發展提供了更多的線索。因此，我們在確定劑量時要注意兩件事，即考慮安全性，當然，療效也將是審查的一個要點。

Our next question comes from Seamus Fernandez with Guggenheim. We'll take our next question that will come from Steve Scala with Cowen.

我們的下一個問題來自古根海姆的謝默斯·費爾南德斯。我們將回答 Steve Scala 和 Cowen 提出的下一個問題。

I have 2 questions. First, on TYK2. Will Bristol conduct a large long-term cardiovascular outcomes trial to fully convince physicians that there is no CV risk? And if not, why not? Bristol's view is clear but prescribers don't seem convinced. And then on Opdivo, does Bristol see any risk from potential new PD-1 entrants such as Lilly's Tyvyt or Novartis' tislelizumab or now the (inaudible) coherus antibody? I assume their primary angle will be price. So what is the risk from that?

我有 2 個問題。首先是TYK2。布里斯托爾是否會進行大型長期心血管結果試驗，以充分說服醫生不存在心血管風險？如果沒有，為什麼不呢？布里斯托爾的觀點很明確，但處方醫生似乎並不相信。然後，在 Opdivo 上，布里斯托爾是否認為潛在的新 PD-1 進入者（例如禮來公司的 Tyvyt 或諾華公司的 tislelizumab 或現在的（聽不清）coherus 抗體）存在任何風險？我認為他們的主要角度是價格。那麼這樣做的風險是什麼？

Maybe I can start off, Steve, with the first question on deucravacritinib. So we have just had the readout of the first Phase III studies in psoriasis. Certainly, data will continue to evolve as we look at the long-term extension studies from psoriasis. We will continue to follow these. We have additional indications ongoing. We do not see the profile that has been described for JAK inhibitors from a [MACE] perspective, VTE perspective, et cetera.

史蒂夫，也許我可以先問關於 deucravacritinib 的第一個問題。我們剛剛公佈了第一個牛皮癬 III 期研究的結果。當然，隨著我們對銀屑病的長期擴展研究，數據將繼續發展。這些我們將持續關注。我們還有更多跡象正在進行中。我們沒有看到從 [MACE] 角度、VTE 角度等角度描述的 JAK 抑製劑的概況。

We have to continue to evaluate. We'll have the discussions with the prescribers, with the health authorities in order to understand what profile is that we need to further investigate. This is not a commercialized drug yet, so in terms of talking about whether the prescribers are convinced or not, I think that is still -- got to be further evaluated, then we are able to present the data and share that profile fully with the community and their perspective with the data in hand. So I think it's too early to define what additional studies to be conducted and we'll continue to follow them very closely.

我們還得繼續評估。我們將與處方醫生和衛生當局進行討論，以了解我們需要進一步調查的情況。這還不是一種商業化的藥物，所以就談論處方者是否相信而言，我認為仍然需要進一步評估，然後我們才能提供數據並與醫生充分分享該資料社區以及他們對現有數據的看法。因此，我認為現在確定要進行哪些額外研究還為時過早，我們將繼續密切關注它們。

Let me pick up on the question on any risk from new entrants on PD-L1 and particularly the concern about price. So first of all, we watch the competitive dynamics of the PD-L1 marketplace extremely carefully, as you can imagine, and something that we've been looking at considerably has been the question of commoditization. That's been with us really since we were approved with Opdivo.

讓我來談談有關 PD-L1 新進入者的任何風險的問題，特別是對價格的擔憂。因此，首先，正如您可以想像的那樣，我們非常仔細地觀察 PD-L1 市場的競爭動態，而我們一直在關注的問題是商品化問題。自從我們獲得 Opdivo 批准以來，這種情況一直伴隨著我們。

From a U.S. standpoint, we actually don't see considerable risk from these new entrants, in part driven by a number of factors: first, oncology continues to be a very data-driven field in the U.S. And so we've got a wealth of data covering both Opdivo and Yervoy, which gives us confidence; second, we've established a very strong position across tumors and, of course, we built very significant capabilities to operate in the competitive context, and I think we're demonstrating that now in both renal cell and lung cancer, for example.

從美國的角度來看，我們實際上並沒有看到這些新進入者帶來相當大的風險，部分原因是多種因素：首先，腫瘤學在美國仍然是一個非常數據驅動的領域，因此我們擁有豐富的財富涵蓋 Opdivo 和 Yervoy 的數據，這給了我們信心；其次，我們已經在腫瘤領域建立了非常強大的地位，當然，我們也建立了非常重要的在競爭環境中運作的能力，我認為我們現在正在腎細胞癌和肺癌等領域證明這一點。

Ex U.S., again, it's something that we're going to continue to stay very focused on. One see that in some markets, you may see some risk of commoditization but those tend to be relatively small markets for us. But in general, I would say we're very confident with our competitive position. We don't see meaningful risk with respect to commoditization from where we sit today, but it's something we'll continue to monitor.

在美國，我們將繼續高度關注這一點。人們發現，在某些市場中，您可能會看到一些商品化的風險，但這些市場對我們來說往往相對較小。但總的來說，我想說我們對我們的競爭地位非常有信心。從我們今天的情況來看，我們沒有看到商品化方面存在重大風險，但我們將繼續監控這一點。

We'll take our next question from Seamus Fernandez with Guggenheim.

我們將回答古根海姆謝默斯·費爾南德斯提出的下一個問題。

So I wanted to just kind of walk through this strategy in multiple myeloma, given the number of mechanisms that you guys have in play and how you see the market evolving? Chris, I think this is likely falling under your auspices more so than anything. So I was just wondering if you could help us understand how you see the treatment of multiple myeloma evolving amidst the transition away from -- or towards Revlimid generics. Obviously, there's lots of opportunities out there, bispecific cell therapy, your CELMoDs business simply about segmenting the market. Or do you see transformational opportunities for potential internal combinations?

因此，考慮到你們發揮作用的機制數量以及您如何看待市場的發展，我想簡單介紹一下多發性骨髓瘤的這一策略？克里斯，我認為這很可能是在你的主持下進行的。所以我只是想知道您是否可以幫助我們了解您如何看待多發性骨髓瘤治療在從來那度胺仿製藥過渡或轉向來那度胺仿製藥的過程中的演變。顯然，那裡有很多機會，雙特異性細胞療法，您的 CELMoD 業務只是為了細分市場。或者您是否看到潛在內部組合的轉型機會？

And then a bigger picture question for Giovanni. Giovanni, we're continuing to see a lot of activity on the BD front from your team. As we think about the next sort of leg of opportunities, are you most focused on sort of Phase II/III opportunities and again, continuing to build out the pipeline in that regard? Is it more additional legs to the stool? Just trying to more fully understand how you're continuing to focus your efforts on enhancing the pipeline and growing and returning the company or -- not returning the company to growth, but extending the growth profile post 2025?

然後是喬瓦尼的一個更大的問題。 Giovanni，我們繼續看到您的團隊在 BD 方面開展了大量活動。當我們考慮下一階段的機會時，您最關注的是第二/第三階段的機會，並繼續在這方面建立管道嗎？凳子上有更多額外的腿嗎？只是想更全面地了解您如何繼續集中精力加強管道建設以及公司的發展和回報，或者不讓公司恢復增長，而是將增長狀況延長到 2025 年之後？

Thanks, Seamus for the question. This is Samit and let me just start with the R&D aspect of multiple myeloma strategy. And then certainly, Chris can fill in the commercial aspects of it. So as you know, beyond the MS, there are 4 classes of medicines that are being developed in multiple myeloma, primarily: cell therapies; certainly, the ADC that has recently been approved and more to follow; there are the CELMoDs, and then they are going to be the combinations as we have also talked about.

謝謝西莫的提問。我是薩米特，讓我從多發性骨髓瘤策略的研發方面開始。當然，克里斯可以填補它的商業方面。如您所知，除了 MS 之外，還有 4 類針對多發性骨髓瘤的藥物正在開發中，主要是：細胞療法；當然，最近已獲得批准的 ADC 以及更多後續產品；還有 CELMoD，然後它們將成為我們也討論過的組合。

Then right now, what we're trying to do is to get to a stage where this disease, which is incurable and in patients who are heavily pretreated in the [first-line plus] where progression (inaudible) remains very low with response rates of 30% or so. We are trying to transform that disease. So from that perspective, cell therapies are going to play a major role, and that's where ide-cel is coming in to begin with, where we have shown the data. We have shown the overall response rate. We've shown the very durable and deep responses and a very manageable safety profile.

那麼現在，我們正在努力做的是達到這樣一個階段：這種疾病是無法治癒的，並且在[一線+]中接受大量預處理的患者中，進展（聽不清）仍然非常低，且緩解率30%左右。我們正在努力改變這種疾病。因此，從這個角度來看，細胞療法將發揮重要作用，這就是 ide-cel 的初衷，我們已經展示了數據。我們已經顯示了總體響應率。我們展示了非常持久和深入的反應以及非常易於管理的安全狀況。

As we look towards the next generation of molecules where the T cell engagers or CELMoDs (inaudible). T cell engagers are going to be also very important. And as we've spoken about earlier, there could be patients who may not be able to receive cell therapies and would be more appropriate in terms of being treated through the T cell engagers. Of course, there are challenges right now with the formulations that we have available. We've seen data from multiple companies coming up, showing that IV administration is associated -- while with good efficacy, there are challenges in terms of finding the right dose of administration schedule from a safety perspective. So we have to be careful in terms of how we go forward with that.

當我們展望下一代 T 細胞參與分子或 CELMoD（聽不清）時。 T 細胞參與者也將非常重要。正如我們之前談到的，有些患者可能無法接受細胞療法，但通過 T 細胞接合劑進行治療會更合適。當然，我們現有的配方目前面臨著挑戰​​。我們已經看到來自多家公司的數據顯示，靜脈注射給藥具有相關性——雖然療效良好，但從安全角度找到正確的給藥方案劑量方面存在挑戰。因此，我們必須謹慎行事。

And so certainly, many others and we are now investigating subcutaneous formulation, where it seems early data from other presentations that we've seen that the efficacy can be maintained. Of course, safety we'll be continuing to reevaluate it. There are small numbers right now but seems to go in the right direction.

當然，我們和許多其他人現在正在研究皮下製劑，從其他演示中獲得的早期數據似乎表明我們已經看到可以維持功效。當然，我們將繼續重新評估安全性。目前數量很少，但似乎正朝著正確的方向發展。

Third parties of CELMoD. And that's where we will show the first of the expansion data later this year. And depending on what the durability and the magnitude of the response are, we might have an opportunity to convey that to health authorities and have a discussion of how to go forward. But from a strategic point of view, higher level, how to move these forward, the next phase of development is definitely going to be combinations. We've shown some of the data already.

CELMoD 的第三方。這就是我們今年晚些時候將展示第一個擴展數據的地方。根據反應的持續時間和程度，我們可能有機會向衛生當局傳達這一信息，並討論如何繼續前進。但從戰略的角度，更高的層面，如何推進這些，下一階段的發展肯定是組合。我們已經展示了一些數據。

If we talk about iberdomide, for example, data at ASH showed us high response rates when combined with the value-added dexamethasone as well as VELCADE with dexamethasone. So those are the strategies moving forward in the earlier line. We are, in a similar way, going to be investigating combinations with ide-cel. And as the data evolves, the T cell engager, we'll look for combinations. The ultimate goal is to move CELMoDs in much earlier line so that we can have the comparisons versus image to be able to ultimately replace them in the longer run, and then, of course, try to move the other modalities also further up in line. But ultimately, yes, there will be segmentation of patients. Some may receive cell therapy, some may receive T cell engagers and there could still be an opportunity for sequencing of these modalities. Chris, do you want to add something?

例如，如果我們談論伊伯多胺，ASH 的數據顯示，當與增值的地塞米松以及 VELCADE 與地塞米松結合使用時，反應率很高。這些是先前的策略。我們將以類似的方式研究與 ide-cel 的組合。隨著數據的發展，T 細胞參與者，我們將尋找組合。最終目標是將 CELMoD 移至更早的位置，以便我們可以與圖像進行比較，以便能夠從長遠來看最終取代它們，然後，當然，嘗試將其他模式也進一步移至前面。但最終，是的，患者將會被細分。有些可能會接受細胞療法，有些可能會接受 T 細胞接合劑，並且仍然有機會對這些方式進行測序。克里斯，你想補充一下嗎？

Actually, I think, Samit, you covered most of it. The only thing I would add is, obviously, as Revlimid and Pomalyst go generic, our focus is going to continue to be on bringing transformational opportunities forward. As you well know, Seamus, there continues to be considerable unmet need, particularly for patients, as they get into later lines of therapy in multiple myeloma. Ide-cel is going to be an important piece of that innovative pipeline that we bring forward, initially in later line therapy, and then as we've discussed, potentially moving that into earlier lines of therapy in a broader patient population.

事實上，我認為，薩米特，你已經涵蓋了大部分內容。我唯一要補充的是，顯然，隨著 Revlimid 和 Pomalyst 通用化，我們的重點將繼續是帶來轉型機會。正如您所知道的，Seamus，仍然存在大量未滿足的需求，特別是對於患者，因為他們進入了多發性骨髓瘤的後期治療。 Ide-cel 將成為我們提出的創新管道的重要組成部分，最初是在後期治療中，然後正如我們所討論的，有可能將其轉移到更廣泛患者群體的早期治療中。

And then as Samit mentioned, the opportunity to launch the next-generation BCMA targets with T cell engagers and potentially the next-generation of small molecules, which we think have the potential to displace today's backbone. And then over time, you could envision these newer therapies being combined and targeting different patient populations across lines of therapy and then also thinking about targeting (inaudible) specific type of drug to the age, performance status or preference of patients. So we're excited about having all of these promising modalities in our portfolio. We think it gives us a unique opportunity to build on our leadership position.

然後，正如 Samit 提到的，有機會推出帶有 T 細胞接合劑的下一代 BCMA 靶標，以及潛在的下一代小分子，我們認為它們有可能取代今天的骨幹。然後，隨著時間的推移，您可以設想將這些較新的療法結合起來，針對不同的患者群體進行不同的治療，然後還考慮根據患者的年齡、體能狀態或偏好來針對（聽不清）特定類型的藥物。因此，我們很高興能夠在我們的產品組合中擁有所有這些有前途的模式。我們認為這為我們提供了一個獨特的機會來鞏固我們的領導地位。

Thank you, Chris. Seamus, this is Giovanni. Let me just rapidly answer your question on business development. So first of all, I see that continuing to be the central pillar of our capital allocation strategy and continue to be focused on areas that are strategically aligned with our commercial presence and research efforts. Obviously, we'll continue to look at things that are scientifically exciting and compelling. And definitely, we will continue to be disciplined from a financial perspective.

謝謝你，克里斯。西莫，這是喬瓦尼。我簡單回答一下你關於業務發展的問題。首先，我認為這將繼續成為我們資本配置戰略的核心支柱，並繼續關注與我們的商業存在和研究工作戰略一致的領域。顯然，我們將繼續關注科學上令人興奮和引人注目的事物。當然，我們將繼續從財務角度遵守紀律。

There will always be a part of our business development strategy that will be about continuing to strengthen and complement our research pipeline and early-stage efforts. You've seen us doing a number of deals in that space last year. I do see that continuing because it's clearly our strategy. At the same time, I've been very clear, JPMorgan, in my presentation, as an example, that as we continue to assess later-stage opportunities, deals like the MyoKardia deal, given the right assets, the opportunity to generate value and the objective to continue to strengthen the growth outlook of the company in the second half of the decade, these are deals we're always going to be interested in.

我們的業務發展戰略中始終有一部分是繼續加強和補充我們的研究渠道和早期工作。去年，您已經看到我們在該領域進行了許多交易。我確實認為這種情況會持續下去，因為這顯然是我們的戰略。與此同時，我以摩根大通為例，在我的演講中非常明確地表示，當我們繼續評估後期機會、MyoKardia 交易等交易時，只要有合適的資產、創造價值的機會以及我們的目標是繼續增強公司在本世紀下半年的增長前景，這些交易是我們始終感興趣的。

Our next question comes from Chris Schott with JPMorgan.

我們的下一個問題來自摩根大通的克里斯·肖特。

Just building on earlier question regarding the TYK2 commercial dynamics and this kind of balance between what you see as a clearly differentiated profile emerging from the JAKs but there being some perception issue, with at least some physicians, in terms of the profile of the drug. How are you thinking that translates from a commercial standpoint? So on 1 hand, do you think that this gets largely addressed through your data presentations, and we can think about a quicker ramp here, given the superior efficacy you're seeing relative to the oral on the market? Or you're anticipating this could be a bit slower launch and that there's going to be a big education component to getting the product established, given that over time, there seems to be a large opportunity, but more of that first kind of initial stage of the ramp.

只是建立在之前有關 TYK2 商業動態的問題和您所看到的 JAK 中出現的明顯差異化特徵之間的這種平衡的基礎上，但至少在一些醫生看來，在藥物的特徵方面存在一些認知問題。從商業角度來看，您認為這如何轉化？因此，一方面，您認為這個問題在很大程度上可以通過您的數據演示來解決嗎？考慮到您所看到的相對於市場上口服藥物的優越功效，我們可以考慮更快地提高產量嗎？或者你預計這可能會慢一些，並且將有一個很大的教育部分來建立產品，考慮到隨著時間的推移，似乎有很大的機會，但更多的是第一種初始階段坡道的。

And the second question I had was on the Factor XIa. I guess, how much will the data from this first study reporting this year (inaudible) or increase or decrease your confidence in the second study? And do we really need to think about both of these Phase II programs reading out before you'll make a decision on moving the asset forward? Or based on this first study, could we see, at least on the -- if the monotherapy setting, the product moving forward?

我的第二個問題是關於 XIa 因子。我猜，今年第一項研究報告的數據（聽不清）會在多大程度上增加或減少您對第二項研究的信心？在您做出推進資產的決定之前，我們真的需要考慮這兩個第二階段計劃嗎？或者根據第一項研究，我們至少可以看到，如果是單一療法，該產品會向前發展嗎？

Chris, let me -- I'll start, and then I'll turn it over to others to comment on the second part of your question. So with respect to the opportunity that we have with TYK and sort of the pace of the commercial execution, look, I think we're excited about the opportunity that we have here. We think that based on the data we've seen from the Phase II as well as both PSO 1 and 2, we have the opportunity to establish TYK as the frontline branded oral of choice for these patients.

克里斯，讓我——我開始，然後我會把它交給其他人來評論你問題的第二部分。因此，就我們與 TYK 合作的機會以及商業執行的節奏而言，我認為我們對這裡擁有的機會感到興奮。我們認為，根據 II 期以及 PSO 1 和 2 期的數據，我們有機會將 TYK 確立為這些患者首選的一線品牌口服藥物。

Now as it relates to how quickly we'll be able to do that, clearly, this is going to be a market where we've got very compelling data versus the omni world that's in the space now. So we think that there, we're going to have an opportunity to educate physicians relatively quickly. Obviously, we're going to have to work through access and the like, which is part of any new launch and that will typically take a bit of time. But we think with respect to our physician versus the existing oral agent, there, we think we have a relatively quick opportunity with a very, very compelling data set against the only existing player there.

現在，因為它關係到我們能夠以多快的速度做到這一點，顯然，這將是一個我們擁有非常引人注目的數據的市場，與目前該領域的全方位世界相比。所以我們認為，在那裡，我們將有機會相對較快地教育醫生。顯然，我們將必須解決訪問等問題，這是任何新發布的一部分，通常需要一些時間。但我們認為，相對於我們的醫生與現有的口服製劑，我們認為我們有一個相對較快的機會，擁有與那裡唯一現有的玩家相比非常非常引人注目的數據集。

Now as we think about additional opportunities to expand from there, that's probably going to take a bit more time as you have competitors that have been established in this marketplace. But that's certainly the way we've been thinking about it at this point. Samit?

現在，當我們考慮從那裡擴展的其他機會時，這可能需要更多的時間，因為您已經在這個市場上建立了競爭對手。但這肯定是我們目前一直在思考的方式。薩米特？

And Chris, just to be very, very short because we know the time is short here and others also have questions, we do believe that both studies have individually very important role to play: to define the dose and the safety profile. The time difference being the readout of those studies is not too long. So I think we will obviously be able to build development plans based out of the first study. Execution will probably take into account both studies. But as I said, the time difference you can readout is not that long. So execution-wise, both data sets will be important.

克里斯，我要說得非常非常簡短，因為我們知道時間很短，其他人也有疑問，我們確實相信這兩項研究都可以發揮非常重要的作用：確定劑量和安全性。這些研究的讀數的時間差並不太長。因此，我認為我們顯然能夠根據第一項研究制定發展計劃。執行可能會考慮這兩項研究。但正如我所說，你能讀出的時間差並沒有那麼長。因此，從執行角度來看，這兩個數據集都很重要。

Our next question comes from Tim Anderson with Wolfe Research.

我們的下一個問題來自沃爾夫研究公司的蒂姆·安德森。

Going back to PD-1 question about commoditization. I want to ask about China specifically. And Roche today painted a cautious picture on the China opportunity due to NRDL and local manufacturer proliferation. I'd be curious to get your view. Is this ever going to be a market that's meaningful for Bristol or other multinationals? And just as importantly, if it's happening in China in the PD-1 category, why wouldn't it happen in other disease categories, oncology or otherwise?

回到 PD-1 關於商品化的問題。我想具體問一下中國的情況。羅氏今天對由於國家醫保目錄和本地製造商激增而帶來的中國機會持謹慎態度。我很想听聽你的看法。這是否會成為一個對布里斯托爾或其他跨國公司有意義的市場？同樣重要的是，如果這種情況發生在中國的 PD-1 類別中，為什麼它不會發生在其他疾病類別、腫瘤學或其他領域呢？

And then second question on Revlimid. Largest product now for the company, goes off-patent next year. Analysts are guessing how to erode it in the first year. We don't know if it's $1 billion or $3 billion down or what exactly. And it'd be great to have some clarity on how to think about first year erosion.

然後是關於 Revlimid 的第二個問題。該公司目前最大的產品將於明年專利到期。分析師正在猜測如何在第一年削弱它。我們不知道到底是減少了 10 億美元還是 30 億美元，還是具體是什麼。如果能夠清楚地了解如何思考第一年的侵蝕，那就太好了。

Let me start on both questions, and I'll ask Chris and David if they want to have. So on China, let me say, first of all, we have a relatively small business in China that we see an opportunity to continue to strengthen our presence in that market, particularly as our pipeline continues to progress and we have launch opportunities going forward in China.

讓我從這兩個問題開始，我會問克里斯和大衛是否願意。關於中國，我要說的是，首先，我們在中國的業務相對較小，我們看到了繼續加強我們在該市場的影響力的機會，特別是隨著我們的管道不斷取得進展，並且我們在未來有推出機會中國。

I would agree that from a NRDL perspective, it is appropriate to be cautious because of the number of PD-1 agents that have been launched at the same time, including the number of local players. And so I share the perspective that the opportunity in China, I would be cautious about. I do believe, though, in a couple of things. So first of all, there are examples of brands in oncology and other therapeutic areas that recently have had a more differentiated profile with fewer local competitors have been able to be included in NRDL reimbursement and built to be meaningful contributors to growth in the market. So I don't think every therapeutic area is the same and every class of drug is the same.

我同意，從國家醫保局的角度來看，由於同時上市的PD-1製劑數量眾多，包括本土企業的數量，因此保持謹慎是適當的。因此，我認為中國的機會我會持謹慎態度。不過，我確實相信一些事情。首先，腫瘤學和其他治療領域的一些品牌最近具有更加差異化的形象，本地競爭對手較少，能夠納入國家醫保目錄報銷範圍，並成為市場增長的有意義的貢獻者。所以我不認為每個治療領域都是一樣的，每類藥物都是一樣的。

And specifically, in our portfolio, we believe there are truly differentiated medicines that can have a very meaningful presence in China. When you look at the medium and the long term, I think actually, the development opportunities in China will continue to grow not only through the government channel, but also over time, the development of commercial insurance for what is a relatively large population of patients that would have access to that.

具體來說，在我們的產品組合中，我們相信存在真正差異化的藥物，可以在中國發揮非常有意義的作用。從中長期來看，我認為實際上中國的發展機會將繼續增長，不僅通過政府渠道，而且隨著時間的推移，針對相對較多患者群體的商業保險的發展那將有權訪問該內容。

So I do see that in the medium term, the composition, if you want, of the marketplace in China in terms of payer dynamics will be more diversified. And I think that will strengthen opportunities across the board. So we continue to be really committed to China.

因此，我確實認為，從中期來看，如果你願意的話，中國市場的支付動態構成將更加多元化。我認為這將全面加強機會。因此，我們將繼續致力於中國市場。

With respect to your question on Revlimid, you -- as you can imagine, we have a number of discussions ongoing. We have litigations along with players that are continuing. We're not going to be in a position to provide multiple year guidance going into the future. But I think we've been pretty clear in articulating our position on the Revlimid erosion beginning in '22. And as we've mentioned, we see the LOE portfolio of Revlimid and Pomalyst representing no more, in fact, less than 10% of the company by 2025. So the evolution of that business, I think it's pretty clear. And from my perspective, what's more important is to really look at the potential for double-digit growth for our continuing business and the growth of the total company between now and 2025. Chris, do you have anything to add on China?

關於您關於 Revlimid 的問題，您可以想像，我們正在進行一些討論。我們與玩家之間的訴訟仍在繼續。我們無法提供未來的多年指導。但我認為我們從 22 年開始就已經非常明確地闡明了我們對 Revlimid 侵蝕的立場。正如我們所提到的，我們認為到 2025 年，Revlimid 和 Pomalyst 的 LOE 組合將不再占公司的 10%，事實上，不到 10%。因此，我認為該業務的演變非常清楚。從我的角度來看，更重要的是真正關注我們持續業務的兩位數增長潛力以及從現在到 2025 年整個公司的增長。克里斯，您對中國有什麼補充嗎？

Giovanni, I think you covered it. Tim, the only thing is that I agree with Giovanni. In the medium to long term, we see significant opportunity. The NRDL is only 1 of the payer channels that are available. As Giovanni mentioned, there's a rapidly emerging commercial and private health care market there. And we think that's going to continue to be an important opportunity for locals and multinational companies. And I wouldn't over-extrapolate the dynamics from PD-1 to other therapeutic categories, just given the intense level of competition that you see in China with those products.

喬瓦尼，我想你已經涵蓋了。蒂姆，唯一的一點是我同意喬瓦尼的觀點。從中長期來看，我們看到了巨大的機遇。國家醫保目錄只是可用的付款渠道之一。正如喬瓦尼提到的，那裡有一個迅速崛起的商業和私人醫療保健市場。我們認為這將繼續成為當地人和跨國公司的重要機會。考慮到中國這些產品的激烈競爭，我不會過度推斷 PD-1 到其他治療類別的動態。

Our next question comes from David Risinger with Morgan Stanley.

我們的下一個問題來自摩根士丹利的大衛·瑞辛格。

I have 2 questions. First, could you discuss why your BCMA orva-cel was dropped? And second, Bristol's peak expectations for Reblozyl are higher than consensus. What do you think investors underappreciate?

我有 2 個問題。首先，您能討論一下您的 BCMA orva-cel 被丟棄的原因嗎？其次，布里斯托爾對 Reblozyl 的最高期望高於共識。您認為投資者低估了什麼？

Maybe I can start off on orva-cel and then certainly pass it on for Chris to comment on Reblozyl. On orva-cel side, we always look at our portfolio overall and ensure that we are going to develop the best medicines and take that forward. Orva-cel, as you know, was a BCMA-directed cell therapy. We have ide-cel as a front runner, which has the data and has been submitted for review and approval, both in the U.S. as well as in EU.

也許我可以從 orva-cel 開始，然後當然可以將其傳遞給 Chris 來評論 Reblozyl。在 orva-cel 方面，我們始終從整體上審視我們的產品組合，並確保我們將開發出最好的藥物並繼續前進。如您所知，Orva-cel 是一種 BCMA 導向的細胞療法。我們有 ide-cel 作為領跑者，它擁有數據並已提交美國和歐盟審查和批准。

When we look at the orva-cel evolution of the data and we put it in terms of the landscape and the evolution of data from outside as well, we believe that ide-cel fits perfectly in terms of further development. And orva-cel's platform becomes very important for the next generation of CAR cell development rather than the medicine -- that particular medicine itself. So therefore, we have not taken orva-cel forward as in the current form and would use the platform for evolution of the evolution of the cell therapies.

當我們審視數據的 orva-cel 演變，並將其放在外部數據的景觀和演變方面時，我們相信 ide-cel 非常適合進一步發展。 Orva-cel 的平台對於下一代 CAR 細胞的開髮變得非常重要，而不是藥物（特定藥物本身）。因此，我們沒有像目前的形式那樣推進orva-cel，而是使用該平台來推動細胞療法的發展。

David, with respect to Reblozyl in terms of the opportunity, the way I think about it is our initial indication in MDS, remember that a relatively smaller percentage of the overall MDS incidents. So in the U.S., for example, the incidence of MDS is roughly 21,000. The on-label population is a relatively small percentage of that, and that's because the initial indication obviously focuses on those patients who are lower risk, ESA-eligible, RF positive and in the second line.

David，就 Reblozyl 的機會而言，我認為這是我們在 MDS 中的最初跡象，請記住，在整個 MDS 事件中所佔的比例相對較小。例如，在美國，MDS 的發病率約為 21,000 例。標籤上的人群所佔比例相對較小，這是因為最初的適應症顯然集中在那些風險較低、符合 ESA 資格、RF 陽性和二線治療的患者。

So the way we think about it is, first and foremost, we've got to continue to drive utilization in the existing indication we have. We think there's continued opportunity there. Then obviously, there's an opportunity to expand within MDS, and we think that the COMMANDS study gives us a meaningful opportunity to both include those patients who are RF negative and move into earlier lines of therapy. And then obviously, beyond MDS, there are other opportunities, beta thal, which is on label today, but then also we have additional opportunities in areas like myofibrosis.

因此，我們的想法是，首先也是最重要的是，我們必須繼續提高現有適應症的利用率。我們認為那裡還有持續的機會。顯然，MDS 有機會進行擴展，我們認為 COMMANDS 研究為我們提供了一個有意義的機會，既可以納入 RF 陰性患者，又可以進入早期治療階段。顯然，除了 MDS 之外，還有其他機會，β thal，今天已上市，但我們在肌纖維化等領域也有其他機會。

Our next question comes from Ronny Gal with Bernstein.

我們的下一個問題來自伯恩斯坦的羅尼·加爾。

Two questions, if I may? First, about the Part D restructuring, you mentioned your support for isolating patients from paying out of pocket. The last (inaudible) we've seen in Congress discuss 20% to 30% responsibility for pharma and the catastrophic part of the insurance and obviously, for giving your portfolio in oral oncology medicine, it will be material. I was wondering if you can just give us a quick update where you believe the base standing, your concern around that issue heard? And is this part of what we should expect?

有兩個問題可以嗎？首先，關於 D 部分重組，您提到了您對隔離患者自付費用的支持。我們在國會看到的最後一次（聽不清）討論了 20% 到 30% 的製藥責任和保險的災難性部分，顯然，對於您在口腔腫瘤醫學領域的投資組合來說，這將是重要的。我想知道您是否可以給我們一個快速的更新，您認為基礎是站穩腳跟的，您對此問題的擔憂被聽到了？這是我們應該期待的一部分嗎？

And second, as we think about the kind of IL-23 TYK2 mechanism coming to IBD, I was wondering if you were able to compare the kind of the efficacy level you're able to achieve with the oral versus the antibodies. And is the gap there small enough that you can compete head-to-head with the IL-23s, assuming that mechanism becomes as dominant as it could be in those indications?

其次，當我們考慮 IBD 中的 IL-23 TYK2 機制時，我想知道您是否能夠比較口服藥物與抗體能夠達到的功效水平。假設該機制在這些適應症中佔據主導地位，那麼差距是否足夠小，足以與 IL-23 正面競爭？

Thank you. Let me start with your question on Part D redesign. So first of all, there is a real need to think about redesigning benefits in a way that is more aligned with the treatments of today and most importantly, that addresses significant affordability issues that are faced by patients because of inappropriate design of benefits and the high co-pay and the high out-of-pocket exposures that patients have.

謝謝。讓我從你關於 D 部分重新設計的問題開始。因此，首先，確實需要考慮以一種更符合當今治療方法的方式重新設計福利，最重要的是，解決患者因福利設計不當和過高而面臨的重大負擔能力問題。共付額和患者自付費用的高風險。

I think it's premature to say exactly where potential legislation in Congress would evolve. We've been very clear that we are supportive of thinking about the evolution of the design. And I think when you look at our portfolio, there is -- we have a very diversified portfolio. So depending on how the coverage gap contribution of the industry evolves, that's currently 70%, and that may actually have an impact on Eliquis, should that be reduced. On the catastrophic side, you are right, some of the specialty oral medicines would be impacted by changes in that area. So it really depends.

我認為現在確切地說國會潛在的立法將如何發展還為時過早。我們非常明確地表示，我們支持思考設計的演變。我認為當你看看我們的投資組合時，你會發現我們擁有非常多元化的投資組合。因此，根據行業的覆蓋缺口貢獻如何演變，目前為 70%，如果減少的話，這實際上可能會對 Eliquis 產生影響。從災難性的角度來看，你是對的，一些專業口服藥物將受到該領域變化的影響。所以這真的取決於。

And when you have a diversified portfolio that may be areas that are impacted negatively, there are areas potentially impacted positively in terms of patients but also in terms of the contribution we already make. So when we look at concrete proposals, we'll be able to assess the impact on our portfolio better. But I think it's important to remember that different medicines in our portfolio today are impacted differently in the various phases of coverage in Medicare. Chris?

當你擁有多元化的投資組合時，這些領域可能會受到負面影響，但也有一些領域可能會在患者方面以及我們已經做出的貢獻方面受到積極影響。因此，當我們查看具體提案時，我們將能夠更好地評估其對我們投資組合的影響。但我認為重要的是要記住，我們今天的投資組合中的不同藥物在醫療保險承保的不同階段受到不同的影響。克里斯？

Sure. So Ronny, we're obviously very enthusiastic about the opportunity that we have to play with potentially multiple drugs in IBD, initially with Zeposia and then pending the data with TYK, potentially an opportunity with deucravacritinib as well. The thing to keep in mind is that while IBD is a competitive space, there continues to be a need for efficacious drugs that have a manageable safety profile. Ultimately, we believe that the competitive dynamics are going to play out along a few dimensions.

當然。所以，Ronny，我們顯然非常熱衷於在 IBD 中使用多種藥物的機會，最初是 Zeposia，然後等待 TYK 的數據，也有可能是 deucravacritinib 的機會。需要記住的是，雖然 IBD 是一個競爭激烈的領域，但仍然需要具有可控安全性的有效藥物。最終，我們相信競爭動態將在幾個方面發揮作用。

Obviously, efficacy, safety, route of administration is very important here. And because this is a chronic disease where patients are going to cycle through multiple products, we think having a novel mechanism of action is important. And so when you look at the 2 broad categories of treatments that are available today, notably biologics and JAK inhibitors, we think our initial foray into this space with Zeposia is favorably positioned.

顯然，功效、安全性、給藥途徑在這裡非常重要。由於這是一種慢性疾病，患者會循環使用多種產品，因此我們認為擁有一種新穎的作用機制非常重要。因此，當您查看當今可用的兩大類治療方法（尤其是生物製劑和 JAK 抑製劑）時，我們認為我們最初通過 Zeposia 進軍這一領域處於有利地位。

For example, we think Zeposia demonstrates efficacy that is competitive with biologics in an oral formulation with an improved safety profile certainly versus the TNF inhibitors. So we think we play very well there. And similarly, with respect to the JAKs, Zeposia administrates efficacy that's generally competitive with JAKs as well and again, an improved safety profile. And across both of those categories being a novel S1P in the space, we think is going to be important.

例如，我們認為 Zeposia 表現出的功效可與口服製劑中的生物製劑相媲美，並且與 TNF 抑製劑相比，安全性也有所提高。所以我們認為我們在那裡打得很好。同樣，對於 JAK，Zeposia 的功效也與 JAK 相當，而且安全性也得到了改善。我們認為，在這兩個類別中，作為該領域新穎的 S1P，這將非常重要。

Thanks, Chris. I know we're running short on time, but I think we could have a few minutes extra, maybe take it to a few more questions. If we can go to the next one, please, Lauren.

謝謝，克里斯。我知道我們的時間不多了，但我想我們可以多花幾分鐘時間，也許可以再問幾個問題。如果我們可以進入下一個，請勞倫。

Our next question comes from Luisa Hector with Berenberg.

我們的下一個問題來自 Luisa Hector 和 Berenberg。

One, just a clarification on the inventory build. You gave the numbers quarter-on-quarter. Can you confirm the year-on-year impact? And then also on the TYK2, we've seen a very positive headline, press releases in psoriasis. I'm wondering when we might see the data, how soon you could file and whether you expect an FDA panel? And just a quick comment, perhaps because in the press releases, you do mentioned the secondary endpoints. Some were met, which implies, some are not met. And I just wondered how crucial they were with their competitive profile of the drug?

一，只是對庫存建設進行澄清。您提供了季度環比的數據。您能否確認同比影響？然後在 TYK2 上，我們看到了一個非常積極的標題，關於牛皮癬的新聞稿。我想知道我們什麼時候可以看到數據，您多久可以提交以及您是否期望 FDA 小組？只是快速評論一下，也許是因為在新聞稿中，您確實提到了次要終點。有些得到了滿足，這意味著有些沒有得到滿足。我只是想知道他們對藥物的競爭特徵有多重要？

Yes. So on the first question, the year-over-year impact is about $200 million in the fourth quarter of inventory build, and that was mainly related to Eliquis and Revlimid. And we expect all of that to come out in the first quarter.

是的。因此，關於第一個問題，第四季度庫存增加的同比影響約為 2 億美元，這主要與 Eliquis 和 Revlimid 有關。我們預計所有這些都將在第一季度出現。

Great. So David, I can take the second part of the question around deucravacritinib very quickly. In terms of the presentation of the data, we anticipate presenting the first of the 2 studies at (inaudible) later this -- I think it's in the second quarter. It's -- I think, in April. And then the second one, we have to find the appropriate conference in the second half of the year so that we can share the data more broadly. So the investigators can share with the community.

偉大的。大衛，我可以很快回答有關 deucravacritinib 的問題的第二部分。就數據的呈現而言，我們預計將在稍後（聽不清）呈現這兩項研究中的第一項——我認為是在第二季度。我想是四月。然後第二個，我們必須在下半年找到合適的會議，以便我們可以更廣泛地共享數據。因此研究人員可以與社區分享。

Second, about the filing, we are working very diligently and it is a priority for us so we do anticipate filing quite rapidly. And of course, as soon as we have the PDUFA date, we will be broadly communicating that and sharing that information with you and others.

其次，關於申請，我們正在非常努力地工作，這是我們的首要任務，因此我們預計申請會很快。當然，一旦我們獲得 PDUFA 日期，我們將廣泛溝通並與您和其他人分享該信息。

Third about the FDA panel, we obviously can't comment on that. We don't know that. We have to continue to have the dialogue with regulatory agencies and they will ultimately decide where they sit on this. So looking forward to that conversation with the health authorities.

第三，關於 FDA 小組，我們顯然不能對此發表評論。我們不知道這一點。我們必須繼續與監管機構進行對話，他們將最終決定他們對此的立場。因此期待與衛生當局的對話。

And last point around the secondary endpoints. As we've said, we've met the primary endpoint and the secondary endpoints. We are very comfortable with the data that we've seen, showing the superiority not only against placebo, but also against OTEZLA. And we've looked at it from a PASI 75 perspective, (inaudible) perspective, PASI 100 perspective. So we are very comfortable with the data that we've seen thus far from both primary and secondary endpoints.

次要端點周圍的最後一點。正如我們所說，我們已經達到了主要終點和次要終點。我們對所看到的數據感到非常滿意，這些數據不僅顯示出相對於安慰劑的優越性，而且還相對於 OTEZLA 的優越性。我們從 PASI 75 的角度、（聽不清）的角度、PASI 100 的角度來看待它。因此，我們對迄今為止從主要和次要終點看到的數據感到非常滿意。

Our next question comes from Andrew Baum with Citi.

我們的下一個問題來自花旗銀行的安德魯鮑姆。

Two questions on the Factor XIa inhibitor, please. First, I'm interested in how quickly you can initiate a Phase III program. I'm assuming given the high probability that you and I both put on the probability of success in the Phase II, the planning for a Phase III program has already begun, given how lengthy many of these programs are going to be. I just want to confirm if that's the case? I'm assuming you've also identified sites as well, given both the company's previous experience.

請教兩個關於 XIa 因子抑製劑的問題。首先，我對啟動第三階段計劃的速度感興趣。我假設，考慮到你和我都認為第二階段成功的可能性很高，考慮到其中許多項目將持續很長的時間，第三階段項目的規劃已經開始。我只是想確認一下是不是這樣？鑑於這兩家公司之前的經驗，我假設您也已經確定了網站。

And then second, you've previously spoken to Escherichia, E. coli syndrome in some of the areas that you want to go on the arterial side. Do you see any subpopulation of atrial fibrillation where you could go head-to-head versus Eliquis? Or should we disregard the atrial fibrillation population completely from any Phase III trial program?

其次，您之前曾在您想要在動脈側進行的某些區域談到過大腸桿菌綜合症。您是否看到任何心房顫動亞群可以與 Eliquis 進行正面交鋒？或者我們應該從任何 III 期試驗計劃中完全忽略心房顫動人群嗎？

Thanks, Andrew. Let me start with the second question first. I don't think you should disregard atrial fibrillation from any trial further. Those are the discussions that we still need to have. And of course, the conversations will need to be had, both with our collaborator, Janssen, as well as the regulatory authorities. But the appropriate competitor would be in the right population. So more to come on that as we gather the data and the conversations gear up.

謝謝，安德魯。我先從第二個問題開始。我認為您不應該在任何試驗中進一步忽視心房顫動。這些是我們仍然需要進行的討論。當然，需要與我們的合作者楊森以及監管機構進行對話。但合適的競爭對手應該在合適的人群中。隨著我們收集數據和對話的進行，還會有更多的內容出現。

In terms of starting again the Phase III studies, one, we need to see the data first from the first trial of the total knee replacement. Both of the companies, of course, want to proceed as quickly as possible, and we certainly honor the excitement that is around there. And of course, these are a priority molecule that we need to move forward. So we will be able to initiate Phase III trials quite rapidly.

就重新開始第三階段研究而言，第一，我們需要首先查看全膝關節置換術第一次試驗的數據。當然，兩家公司都希望盡快開展工作，我們當然尊重周圍的興奮。當然，這些是我們需要向前推進的優先分子。因此，我們將能夠相當迅速地啟動第三階段試驗。

You very correctly said, both companies have the expertise in conducting these trials and with the prior experiences that we have, we will be able to initiate very quickly. But certainly looking forward to see the first data. I cannot share time lines yet because we have to obviously collaborate with Janssen to be able to define those. But as soon as those are available, those will be shared in due course as well.

您說得非常正確，兩家公司都擁有進行這些試驗的專業知識，並且憑藉我們之前的經驗，我們將能夠非常快速地啟動。但當然期待看到第一個數據。我還不能分享時間表，因為我們顯然必須與楊森合作才能定義這些時間表。但一旦這些可用，它們也將在適當的時候共享。

Thank you, Samit, and thanks, everyone. Let me just make a couple of comments. First of all, let me say, I am excited that 2020 was a really important year for us. It was a great year, the first year for us as a combined company. Our performance was strong during a challenging year with so many different points of view. And we've established a really strong foundation for our new company.

謝謝你，薩米特，謝謝大家。讓我簡單發表幾點評論。首先，我很高興 2020 年對我們來說是非常重要的一年。這是偉大的一年，是我們作為合併公司的第一年。在充滿挑戰的一年裡，我們的表現非常強勁，有很多不同的觀點。我們已經為新公司奠定了堅實的基礎。

There is solid momentum in our business going into 2021, and that's reflected in our outlook for '21 and the guidance we provided today. We feel really good about the company that we're building, the way in which we are executing and delivering on the value drivers of the acquisition of Celgene. We see all significant opportunities for sustained long-term growth ahead and the acceleration of the renewal of our portfolio. And we look forward to continuing to update all of you as we make progress by continuing to remain focused on execution and advancing the many priorities we have as a company. I know the team will be available to answer any additional questions. And I'd like to thank you for participating in our call today. Thank you.

進入 2021 年，我們的業務勢頭強勁，這反映在我們對 21 年的展望以及我們今天提供的指導中。我們對我們正在建立的公司以及我們執行和實現收購 Celgene 的價值驅動因素的方式感到非常滿意。我們看到了未來持續長期增長和加速更新我們的投資組合的所有重大機會。我們期待著通過繼續專注於執行和推進我們作為一家公司的許多優先事項來取得進展，繼續向大家通報最新情況。我知道團隊將可以回答任何其他問題。我要感謝您參加我們今天的電話會議。謝謝。

And that does conclude today's conference. We thank you for your participation. You may now disconnect.

今天的會議到此結束。我們感謝您的參與。您現在可以斷開連接。