施貴寶 (BMY) 2021 Q4 法說會逐字稿

Good day, everyone, and welcome to the Bristol-Myers Squibb 2021 Fourth Quarter Results Conference Call. Today's conference is being recorded.

大家好，歡迎參加百時美施貴寶 2021 年第四季度業績電話會議。今天的會議正在錄製中。

At this time, I'd like to turn the call over to Mr. Tim Power, Vice President, Investor Relations. Please go ahead, sir.

現在，我想將電話轉給投資者關係副總裁 Tim Power 先生。請繼續，先生。

Thank you, Alan, and good morning, everyone. Thanks for joining us this morning for our Fourth Quarter 2021 Earnings Call.

謝謝艾倫，大家早上好。感謝您今天早上參加我們的 2021 年第四季度收益電話會議。

Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. Also participating in today's call are Chris Boerner, our Chief Commercialization Officer; and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development.

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；以及我們的首席醫療官兼全球藥物開發主管 Samit Hirawat。

As you'll note, we posted slides to bms.com that you can follow along with for Giovanni and David's remarks. And before we get started, I'll read our forward-looking statement.

您會注意到，我們在 bms.com 上發布了幻燈片，您可以通過這些幻燈片了解 Giovanni 和 David 的言論。在我們開始之前，我將閱讀我們的前瞻性聲明。

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，我們特別不承擔任何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 certain non-GAAP financial measures to the most comparable GAAP measures are available on 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。 bms.com 上提供了某些非 GAAP 財務指標與最具可比性 GAAP 指標的調節表。

And with that, I'll now hand over to Giovanni.

現在，我將把工作交給喬瓦尼。

Thank you, Tim, and good morning, everyone. Let's start with our fourth quarter performance on Slide 4. I'm pleased to report we delivered another strong quarter, building on our very good performance throughout 2021. Our commercial results were strong across the portfolio with robust performance in our continuing business, driven by Eliquis and accelerated growth for Opdivo as well as continued demand growth for our new products.

謝謝蒂姆，大家早上好。讓我們從幻燈片 4 上的第四季度業績開始。我很高興地報告，在 2021 年全年出色業績的基礎上，我們又實現了強勁的季度業績。在整個投資組合中，我們的商業業績強勁，持續業務表現強勁，這得益於Eliquis 和 Opdivo 的加速增長以及我們新產品的持續需求增長。

The launch of Zeposia in ulcerative colitis is progressing well in the U.S., and we obtained European approval during the quarter. We are pleased with continued demand growth for Reblozyl in ESA refractory MDS and transfusion-dependent beta-thal. And our cell therapies, Breyanzi and Abecma, continue to see significant demand while we remain focused on broadening supply and expanding indications over time.

用於治療潰瘍性結腸炎的 Zeposia 在美國的上市進展順利，我們在本季度獲得了歐洲的批准。我們對 Reblozyl 在 ESA 難治性 MDS 和輸血依賴性β-thal 中的需求持續增長感到高興。我們的細胞療法 Breyanzi 和 Abecma 繼續看到巨大的需求，同時我們仍然專注於隨著時間的推移擴大供應和擴大適應症。

We are advancing our strategy and delivered key pipeline milestones in the fourth quarter. This enables us to help more patients, accelerate the renewal of our portfolio and support our growth outlook. Let me highlight some key achievements.

我們正在推進我們的戰略，並在第四季度實現了關鍵的管道里程碑。這使我們能夠幫助更多患者，加速我們產品組合的更新並支持我們的增長前景。讓我強調一些關鍵成就。

We submitted applications for the deucravacitinib in the U.S., EU and Japan, which position us well to grow our presence in immunology. We are excited about the potential of the deucravacitinib as the oral standard of care in moderate to severe psoriasis and various other autoimmune diseases.

我們在美國、歐盟和日本提交了 deucravacitinib 的申請，這使我們能夠很好地擴大我們在免疫學領域的影響力。我們對 deucravacitinib 作為中度至重度牛皮癬和各種其他自身免疫性疾病的口服標準治療的潛力感到興奮。

We are expanding our cardiovascular portfolio and presented exciting data at AHA for Milvexian, which we see as the next-generation anti-thrombotic with a $5 billion-plus non-risk-adjusted revenue opportunity.

我們正在擴大我們的心血管產品組合，並在 AHA 上展示了 Milvexian 的令人興奮的數據，我們認為這是下一代抗血栓藥物，具有超過 50 億美元的非風險調整收入機會。

We presented important updates at ASH on our hematology pipeline. This includes encouraging data for iberdomide and 480, our exciting new multiple myeloma CELMoD agents. These have the potential to replace Revlimid and Pomalyst over time.

我們在 ASH 上展示了我們血液學產品線的重要更新。其中包括伊伯多胺和 480（我們令人興奮的新型多發性骨髓瘤 CELMoD 藥物）的令人鼓舞的數據。隨著時間的推移，這些藥物有可能取代 Revlimid 和 Pomalyst。

Importantly, the TRANSFORM data for Breyanzi in second-line B-cell lymphoma showed practice-changing benefit compared to the current standard of care. We continue to see Breyanzi as one of the key growth drivers for the company with over $3 billion in non-risk-adjusted revenue potential.

重要的是，與當前的護理標準相比，Breyanzi 在二線 B 細胞淋巴瘤中的 TRANSFORM 數據顯示出改變實踐的益處。我們仍然將 Breyanzi 視為該公司的主要增長動力之一，其非風險調整後收入潛力超過 30 億美元。

Our strong execution helped drive solid financial performance in the fourth quarter. We reported 8% sales growth and double-digit non-GAAP EPS growth. Our strong cash flow and financial strength provide us with significant financial flexibility. This enables us to continue prioritizing disciplined business development opportunities while paying down debt and expanding shareholder distributions.

我們強大的執行力幫助推動了第四季度穩健的財務業績。我們報告銷售額增長 8%，非 GAAP 每股收益增長兩位數。我們強大的現金流和財務實力為我們提供了顯著的財務靈活性。這使我們能夠繼續優先考慮嚴格的業務發展機會，同時償還債務和擴大股東分配。

We also introduced our 2022 guidance last month, and I'll let David speak to the details in a moment. What's important is that we are guiding to growth this year, with low double-digit growth from our continuing business, more than offsetting the Revlimid revenue impact from generics in the U.S. and internationally.

上個月我們還介紹了 2022 年指導意見，稍後我將讓 David 詳細介紹。重要的是，我們今年的增長目標是持續業務的兩位數低增長，足以抵消來那度胺對美國和國際仿製藥收入的影響。

Turning to our 2021 execution scorecard on Slide 5. At the beginning of last year, I outlined a number of milestones that we believed would be important to our future, including opportunities to renew our portfolio and grow our business during the decade. I am pleased to report we've made great progress. We returned Opdivo's growth, successfully launched multiple new products and produced key expansion data sets for several assets. This record of execution across the company further strengthens my confidence in our ability to continue to renew our portfolio and grow in the future.

轉向幻燈片 5 上的 2021 年執行記分卡。去年初，我概述了一些我們認為對我們的未來非常重要的里程碑，包括在這十年中更新我們的投資組合和發展我們的業務的機會。我很高興地報告我們已經取得了很大進展。我們回報了 Opdivo 的增長，成功推出了多個新產品，並為多個資產生成了關鍵的擴展數據集。整個公司的執行記錄進一步增強了我對我們繼續更新產品組合併在未來發展的能力的信心。

We know we must remain focused on advancing our pipeline to accelerate the renewal of our portfolio. And on Slide 6, you can see there are multiple catalysts ahead during 2022. The 2022 milestones include expected approvals and launches for 3 exciting first-in-class medicines: Mavacamten, deucravacitinib and relatlimab. We believe that all of this have the potential to further strengthen the commercial opportunity for our new product portfolio and support our growth outlook. We expect that each of these assets has at least $4 billion of revenue potential at the end of the decade on a non-risk-adjusted basis. We look forward to keeping you updated on our progress throughout the year.

我們知道，我們必須繼續專注於推進我們的產品線，以加速我們產品組合的更新。在幻燈片 6 上，您可以看到 2022 年有多種催化劑。2022 年的里程碑包括 3 種令人興奮的一流藥物的預期批准和上市：Mavacamten、deucravacitinib 和 relatlimab。我們相信，所有這些都有可能進一步增強我們新產品組合的商業機會，並支持我們的增長前景。我們預計，在非風險調整的基礎上，到本十年末，這些資產中的每一項都具有至少 40 億美元的收入潛力。我們期待向您通報我們全年的最新進展。

Looking to the future, Slide 7 summarizes our perspective of how all of this comes together to support the growth of the company moving forward. We expect the growth in our continuing business will enable us to more than offset key LOEs through 2025, with continued growth of our in-line brands and $10 billion to $13 billion of additional sales expected from our new product portfolio.

展望未來，幻燈片 7 總結了我們對所有這些如何共同支持公司未來發展的看法。我們預計，我們的持續業務增長將使我們能夠在 2025 年之前抵消主要的 LOE，同時我們的同線品牌將持續增長，新產品組合預計將帶來 100 億至 130 億美元的額外銷售額。

In the second half of the decade, with a broad and expanding product portfolio, we will have multiple paths to achieving our growth objective from 2025 to 2029. As we've said, we expect more than $25 billion in non-risk-adjusted revenue potential from the current new product portfolio in '29, with additional contributions coming from our pipeline, including assets like Milvexian and our exciting CELMoD agents.

在這個十年的後半段，憑藉廣泛且不斷擴大的產品組合，我們將有多種途徑實現 2025 年至 2029 年的增長目標。正如我們所說，我們預計非風險調整收入將超過 250 億美元29 年當前新產品組合的潛力，以及來自我們管道的額外貢獻，包括 Milvexian 等資產和我們令人興奮的 CELMoD 代理。

As we continue our journey to renew our business and grow through the impact of LOEs starting this year, I'm increasingly excited about the future of Bristol-Myers Squibb. With that, I'll turn it over to David to walk you through the financials. David?

從今年開始，隨著我們繼續推進業務更新並通過 LOE 的影響實現增長，我對百時美施貴寶的未來越來越感到興奮。接下來，我將把它交給 David，讓他帶您了解財務狀況。大衛？

Thank you, Giovanni, and thank you all for joining our call today. I'd like to start with our strong top line performance on Slide 9. We closed out the year with another great quarter across our key franchises. Revenues grew high single digits versus prior year, which was driven primarily by increased demand for our in-line and new product portfolios.

謝謝喬瓦尼，也感謝大家今天加入我們的電話會議。我想從幻燈片 9 上我們強勁的營收表現開始。我們的主要特許經營業務又以一個出色的季度結束了這一年。與上一年相比，收入出現高個位數增長，這主要是由於對我們的在線產品和新產品組合的需求增加所致。

Now let's turn to some product specifics, starting with Eliquis on Slide 10. Eliquis continued to deliver extraordinary growth, with global sales up 20% for both the fourth quarter and the full year. In the U.S., fourth quarter sales increased 22% versus prior year, driven primarily by total prescription growth of 13%. Internationally, Eliquis sales growth continues to be driven by increased share across all key markets, and the brand remains the #1 OAC in multiple countries.

現在讓我們來談談一些產品細節，首先從幻燈片 10 上的 Eliquis 開始。Eliquis 繼續實現非凡的增長，第四季度和全年的全球銷售額均增長 20%。在美國，第四季度銷售額較上年同期增長 22%，這主要是由於總處方量增長 13%。在國際上，Eliquis 的銷售增長繼續受到所有主要市場份額增加的推動，並且該品牌仍然是多個國家排名第一的 OAC。

Looking forward, the growth outlook for Eliquis remains strong as we continue to grow the oral anticoagulant class and increase our share within the class. As a reminder, the first quarter of 2021 did experience a onetime favorable true-up in the U.S. of approximately $160 million that will not repeat in Q1 of '22.

展望未來，隨著我們繼續擴大口服抗凝劑類別並增加我們在該類別中的份額，Eliquis 的增長前景仍然強勁。提醒一下，2021 年第一季度美國確實經歷了一次有利的調整，約為 1.6 億美元，但這種情況在 22 年第一季度不會重演。

Moving to Opdivo's performance on Slide 11. We are very pleased with the accelerated momentum, growing 11% globally versus prior year. This is driven by strong demand, particularly for our new launch indications.

轉向幻燈片 11 中 Opdivo 的表現。我們對加速的勢頭感到非常滿意，與去年相比，全球增長了 11%。這是由強勁需求推動的，尤其是對我們新推出的適應症的需求。

In the U.S., fourth quarter revenues were strong, up 16% versus prior year. Growth was primarily attributable to demand in metastatic indications, including first-line lung, first-line renal and first-line gastric cancers as well as adjuvant indications with the approvals of adjuvant esophageal and adjuvant bladder cancers in 2021.

在美國，第四季度收入強勁，比去年同期增長 16%。增長主要歸因於轉移適應症的需求，包括一線肺癌、一線腎癌和一線胃癌以及輔助適應症，其中輔助食管癌和輔助膀胱癌將於2021年獲得批准。

Internationally, fourth quarter revenues grew 5% versus prior year, driven largely by demand for new indications and expanded access primarily in emerging markets. More broadly, we continue to see uptake of our new launches in lung and renal cancer in Germany and Japan. And we secured reimbursement in Italy and Spain in the fourth quarter. As we look forward, we continue to expect further growth for Opdivo as we secure additional reimbursement for recent approvals. We're in a strong position to continue to grow Opdivo and look forward to additional approvals this year and in the years ahead.

在國際上，第四季度收入較去年同期增長 5%，這主要是由於新興市場對新適應症的需求和擴大准入的需求推動的。更廣泛地說，我們繼續看到德國和日本對肺癌和腎癌新產品的採用。我們在第四季度在意大利和西班牙獲得了補償。展望未來，我們繼續預計 Opdivo 會進一步增長，因為我們獲得了最近批准的額外報銷。我們有能力繼續發展 Opdivo，並期待今年和未來幾年獲得更多批准。

Now let's turn to our IMiD portfolio on Slide 12, starting with Revlimid. Fourth quarter revenues grew 1% globally versus prior year and grew 6% for the full year with sales of approximately $12.8 billion. As we enter into the first year of generic entry for Revlimid, I want to remind everyone of our expectations for Revlimid sales in 2022 and beyond. We expect Revlimid sales of $9.5 billion to $10 billion in 2022. Of these sales, we expect roughly 75% to come from the U.S. and the remaining from ex U.S. markets.

現在讓我們轉向幻燈片 12 上的 IMiD 產品組合，從 Revlimid 開始。第四季度全球收入較去年同期增長 1%，全年收入增長 6%，銷售額約為 128 億美元。隨著我們進入來那度胺仿製藥進入的第一年，我想提醒大家我們對來那度胺 2022 年及以後銷售的預期。我們預計 2022 年 Revlimid 銷售額將達到 95 億至 100 億美元。其中，我們預計大約 75% 來自美國，其餘來自美國以外市場。

As we think about generic entry this year, we expect sales variability quarter-to-quarter based on the timing of how generic competitors fulfill their annual volumes. For the first quarter, our best projection for global Revlimid sales is approximately $2.5 billion. Beyond '22 through 2025, although there's still uncertainty due to ongoing litigation, we view an annual stepdown of roughly $2 billion to $2.5 billion per year as a reasonable projection.

當我們考慮今年的仿製藥進入時，我們預計銷售額會根據仿製藥競爭對手完成年度銷量的時間而出現季度與季度的變化。對於第一季度，我們對 Revlimid 全球銷售額的最佳預測約為 25 億美元。從 22 世紀到 2025 年，儘管由於正在進行的訴訟仍然存在不確定性，但我們認為每年大約減少 20 億至 25 億美元是一個合理的預測。

Now on to Pomalyst. Global sales in the fourth quarter were up 2%. Sales were primarily driven by demand for triple-based therapies in ex U.S. markets and fewer selling days in the U.S. We continue to expect growth for Pomalyst as treatments move to earlier lines of therapy and more triplet-based therapies are approved with longer duration of treatment. As it relates to U.S. IP for Pomalyst, we are pleased that there is now no outstanding litigation. At this point, we don't expect generic entry in the U.S. market prior to the first quarter of 2026.

現在談談 Pomalyst。第四季度全球銷售額增長 2%。銷售主要受到美國以外市場對三聯療法的需求以及美國銷售天數減少的推動。隨著治療轉向早期療法以及更多三聯療法獲得批准且治療持續時間更長，我們繼續預計 Pomalyst 的增長。由於它涉及 Pomalyst 的美國知識產權，我們很高興現在沒有未決訴訟。目前，我們預計仿製藥不會在 2026 年第一季度之前進入美國市場。

Now let's move on to our new product portfolio on Slide 13. We are very pleased with the momentum and feedback we're receiving on our new product portfolio. These products contributed over $350 million in the fourth quarter and $1.1 billion for the full year.

現在讓我們繼續討論幻燈片 13 上的新產品組合。我們對新產品組合的勢頭和收到的反饋感到非常滿意。這些產品第四季度貢獻了超過 3.5 億美元，全年貢獻了 11 億美元。

Let me provide some color on each launch individually, starting with Reblozyl, which generated global revenues of just over $550 million in 2021, more than doubling its revenues over last year. In the U.S., full year sales grew 87% versus prior year, primarily due to continued demand in ESA refractory MDS patients.

讓我對每次發布的產品進行一些說明，首先是 Reblozyl，該產品 2021 年的全球收入略高於 5.5 億美元，是去年收入的兩倍多。在美國，全年銷售額較上年增長 87%，這主要是由於 ESA 難治性 MDS 患者的持續需求。

Demand continued to grow in the fourth quarter. Sequentially, revenue was impacted by onetime favorable inventory build in the third quarter of approximately $20 million to $25 million. Our focus remains on treating new patients earlier in their treatment journey upon ESA failure as well as ensuring physicians titrate the patients up to receive the appropriate dose for sustained benefit.

第四季度需求繼續增長。隨後，收入受到第三季度一度有利的庫存建設的影響，約為 2000 萬至 2500 萬美元。我們的重點仍然是在 ESA 失敗的治療過程中早期治療新患者，並確保醫生滴定患者以獲得持續獲益的適當劑量。

Internationally, we continue to launch in additional countries and expect to continue to do so in 2022, helping more patients and driving additional growth for the brand.

在國際上，我們繼續在更多國家推出產品，並預計在 2022 年繼續這樣做，幫助更多患者並推動該品牌的進一步增長。

Now moving to our cell therapy launches, Abecma and Breyanzi. Abecma generated revenues of $164 million since its launch in May of last year. Revenues reflect very strong demand for the first-ever BCMA cell therapy. As noted in the past, demand continues to be very robust, and we're working hard to expand capacity. We expect first quarter revenues to be largely similar to the fourth quarter.

現在轉向我們的細胞療法產品 Abecma 和 Breyanzi。自去年 5 月推出以來，Abecma 創造了 1.64 億美元的收入。收入反映出對首個 BCMA 細胞療法的強勁需求。正如過去所指出的，需求仍然非常強勁，我們正在努力擴大產能。我們預計第一季度的收入將與第四季度基本相似。

Turning to our CD19 cell therapy, Breyanzi. Physicians continue to recognize Breyanzi's best-in-class profile for relapsed/refractory patients. We look forward to moving Breyanzi up the treatment paradigm in the second-line setting with remarkable EFS data presented from our TRANSFORM study at ASH. And we look forward to bringing this treatment to second-line patients in the U.S. this year.

轉向我們的 CD19 細胞療法，Breyanzi。醫生們繼續認可 Breyanzi 對於復發/難治性患者的一流療效。我們期待通過我們在 ASH 的 TRANSFORM 研究中提供的出色的 EFS 數據，將 Breyanzi 提升到二線治療模式。我們期待今年將這種治療方法帶給美國的二線患者。

Now moving to Zeposia. Global sales for the year were $134 million, primarily driven by our multiple sclerosis indication. In the U.S., the MS launch continues to go well. Zeposia remains the leading S1P in written prescriptions, and we remain focused on establishing Zeposia not only as the S1P of choice, but also the oral treatment of choice.

現在搬到澤波西亞。今年的全球銷售額為 1.34 億美元，主要由我們的多發性硬化症適應症推動。在美國，MS 的推出繼續進展順利。 Zeposia 仍然是書面處方中領先的 S1P，我們仍然致力於將 Zeposia 打造為不僅是首選 S1P，而且是首選口服治療藥物。

We continue to be pleased with the progress we have made on patient conversion, with significant decrease in time to commercial therapy.

我們仍然對患者轉化方面取得的進展感到滿意，商業治療的時間顯著縮短。

Our early UC launch is continuing to gain traction with a leading share of voice and increased overall volume. Physicians are responding well to the profile, and we're encouraged by their intent to prescribe. We are working on building volume and growing access and reimbursement. We expect to have increased contribution from UC in the second half of this year and expanding in 2023.

我們早期推出的 UC 憑藉領先的語音份額和不斷增加的整體音量繼續獲得關注。醫生們對這份資料反應良好，我們對他們開處方的意願感到鼓舞。我們正在努力擴大數量並增加獲取和報銷。我們預計 UC 的貢獻將在今年下半年有所增加，並在 2023 年擴大。

Internationally, Zeposia continues to gain momentum in MS as the product gets additional reimbursement in more markets and benefited from certain year-end stocking. We are very pleased with the recent EMA approval of UC in December and look forward to securing access and reimbursement for this indication to drive further growth for the brand.

在國際上，Zeposia 在 MS 領域繼續保持強勁勢頭，因為該產品在更多市場獲得了額外報銷，並受益於某些年終備貨。我們對 UC 在 12 月獲得 EMA 批准感到非常高興，並期待獲得該適應症的使用權和報銷，以推動該品牌的進一步增長。

Lastly, on Onureg the U.S., we continue to make progress on establishing the product for patients with complete remission following intensive chemotherapy. Our focus remains on shaping the maintenance segment and increasing adoption and patient adherence.

最後，在美國Onureg，我們繼續在為強化化療後完全緩解的患者開發產品方面取得進展。我們的重點仍然是塑造維護領域並提高采用率和患者依從性。

Overall, I'm pleased with our new product portfolio performance and look forward to 3 additional approvals expected this year. We are launch-ready for relatlimab and mavacamten with PDUFA dates in March and April, and we're on track for deucravacitinib's launch in September.

總體而言，我對我們的新產品組合表現感到滿意，並期待今年預計將獲得另外 3 項批准。我們已做好 relatlimab 和 mavacamten 的上市準備， PDUFA 日期為 3 月和 4 月，並且 deucravacitinib 有望在 9 月上市。

Now switching gears to our fourth quarter P&L on Slide 14. Having just covered sales performance, let me walk you through a few non-GAAP key line items. Operating expenses increased versus prior quarter due to timing of MS&A investments that shifted from -- to the fourth quarter, as noted in October. MS&A decreased versus prior year due to some incremental and accelerated investments to support our business in 2020. The fourth quarter effective tax rate was impacted by earnings mix. And as a result, the strong performance in the quarter, non-GAAP EPS increased approximately 25% year-over-year.

現在切換到幻燈片 14 上的第四季度損益表。剛剛介紹了銷售業績，讓我帶您了解一些非 GAAP 關鍵項目。正如 10 月份指出的那樣，由於 MS&A 投資的時間從 - 轉移到了第四季度，運營費用較上一季度有所增加。由於 2020 年支持我們業務的一些增量和加速投資，MS&A 較上年有所下降。第四季度有效稅率受到盈利組合的影響。因此，本季度表現強勁，非 GAAP 每股收益同比增長約 25%。

Moving to the balance sheet and capital allocation on Slide 15. We continue to generate a significant amount of cash from operations with approximately $4 billion in the fourth quarter. We ended the quarter in a strong liquidity position with approximately $17 billion in cash and marketable securities. Our capital allocation priorities remain unchanged. Business development remains our top priority to further renew and diversify our portfolio. And we are also focused on reducing debt and returning capital to shareholders.

轉到幻燈片 15 上的資產負債表和資本配置。第四季度我們繼續從運營中產生大量現金，約為 40 億美元。本季度結束時，我們的流動性狀況良好，擁有約 170 億美元的現金和有價證券。我們的資本配置重點保持不變。業務發展仍然是我們進一步更新和多元化投資組合的首要任務。我們還致力於減少債務並向股東返還資本。

We have executed several business development deals last year, bringing in differentiated early stage assets. We have the financial strength to be size-agnostic, but we are particularly interested in early science and midsized bolt-on deals.

去年，我們執行了幾項業務開發交易，引入了差異化的早期資產。我們擁有不分規模的財務實力，但我們對早期科學和中型補充交易特別感興趣。

As it relates to debt. In 2021, we reduced gross debt by over $6 billion and remain committed to maintaining a strong investment-grade credit rating.

因為它與債務有關。 2021 年，我們將總債務減少了超過 60 億美元，並繼續致力於維持強勁的投資級信用評級。

Lastly, as it relates to returning capital to shareholders, we recently grew the dividend by over 10%, which was our 13th consecutive increase. Additionally, we increased our share repurchase authorization by $15 billion and plan to execute a $5 billion ASR this quarter.

最後，由於涉及向股東返還資本，我們最近將股息增加了 10% 以上，這是我們連續 13 次增加股息。此外，我們將股票回購授權增加了 150 億美元，併計劃本季度執行 50 億美元的 ASR。

Now turning to our 2022 non-GAAP guidance at current exchange rates on Slide 16. As announced last month, we expect '22 revenues to be approximately $47 billion, representing low single-digit growth over 2021. Growth from our continuing business will more than offset the revenue impact from Revlimid and Abraxane LOEs. We expect key LOE brand sales to be approximately $10.5 billion. And our continuing business, which represents our in-line and new product portfolios, is expected to grow low-double digit and contribute approximately $36.5 billion.

現在轉向幻燈片 16 上按當前匯率計算的 2022 年非 GAAP 指引。正如上個月宣布的那樣，我們預計 22 年收入約為 470 億美元，比 2021 年實現低個位數增長。我們持續業務的增長將超過抵消 Revlimid 和 Abraxane LOE 的收入影響。我們預計 LOE 主要品牌銷售額約為 105 億美元。我們的持續業務（代表我們的內嵌產品和新產品組合）預計將實現低兩位數增長，貢獻約 365 億美元。

As it relates to our line item guidance for the year. We expect our gross margin to be approximately 78% and our total operating expenses to be in line with 2021 expenses, and we project our tax rate to be approximately 16.5%.

因為它與我們今年的訂單項目指導有關。我們預計我們的毛利率約為 78%，我們的總運營費用將與 2021 年的費用保持一致，我們預計我們的稅率約為 16.5%。

Finally, also communicated earlier this year, we expect non-GAAP EPS to grow faster than sales and be between $7.65 and $7.95. As it relates to our share count, I'd like to provide a little color as we plan to execute the $5 billion ASR. We ended the year with approximately 2.2 billion diluted shares outstanding. We will be executing the ASR later this quarter, which means we will get a majority, but not all of the benefit on diluted share count this year.

最後，我們還在今年早些時候表示，預計非 GAAP 每股收益將快於銷售額增長，在 7.65 美元至 7.95 美元之間。由於這與我們的股份數量有關，因此我想在我們計劃執行 50 億美元的 ASR 時提供一些信息。截至年底，我們的稀釋後流通股數量約為 22 億股。我們將在本季度晚些時候執行 ASR，這意味著我們將獲得今年稀釋後股票數量的大部分（但不是全部）收益。

Lastly, given this is the first quarter of generic entry for Revlimid, we thought it would be helpful to provide some perspective on revenue for the first quarter. In addition to the approximately $2.5 billion of Revlimid sales I mentioned previously, we are projecting total global first quarter sales to range from $11 billion to $11.5 billion.

最後，鑑於這是 Revlimid 仿製藥進入的第一季度，我們認為提供一些有關第一季度收入的觀點將有所幫助。除了我之前提到的 Revlimid 約 25 億美元的銷售額之外，我們預計第一季度全球總銷售額將在 110 億美元至 115 億美元之間。

So before I turn it over to question and answer, I just want to thank our teams around the world for delivering these remarkable results in 2021. These results and our guidance for 2022 demonstrate the financial strength of the business and the renewal of our portfolio, which positions us well for long-term growth.

因此，在我開始問答之前，我只想感謝我們世界各地的團隊在 2021 年取得了這些卓越的成果。這些成果和我們對 2022 年的指導表明了我們業務的財務實力和我們投資組合的更新，這為我們的長期增長奠定了良好的基礎。

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, David. Alan, can we go to our first question, please?

謝謝，大衛。艾倫，我們可以回答第一個問題嗎？

Certainly, sir. We'll go first to Seamus Fernandez with Guggenheim.

當然，先生。我們首先去古根海姆的謝默斯·費爾南德斯 (Seamus Fernandez)。

So first question is just on your factor XI. Just wanted to check in on timing of the potential update from your Phase II study.

所以第一個問題只是關於你的因素 XI。只是想檢查一下您的第二階段研究的潛在更新的時間。

And just wanted to get a sense of where your expectations are. As we've spoken with thought leaders in the space, the hope is that the increase in the dosing or the stepped-up dosing would result in no bleeding increase, but with roughly a 15%, potentially 20% benefit, on stroke. How does that sort of fit with your expectations? And can you guys help us understand a little bit better the opportunity to open up this potentially new market and how you see the size of the opportunity should that profile be achieved? And do you agree with those views?

只是想了解一下您的期望在哪裡。正如我們與該領域的思想領袖交談的那樣，我們希望增加劑量或逐步加大劑量不會導致出血增加，但對中風有大約 15%、可能是 20% 的益處。這與您的期望相符嗎？你們能否幫助我們更好地了解開拓這個潛在新市場的機會，以及您如何看待實現這一目標所帶來的機會的規模？您同意這些觀點嗎？

And then second, just on your -- we just had the filing of the Cytokinetics competitor compound. Can you just talk a little bit about the competitive landscape as you think about the opportunity for mavacamten versus other competitor compounds?

其次，我們剛剛收到了 Cytokinetics 競爭對手化合物的備案。當您考慮 mavacamten 與其他競爭對手化合物相比的機會時，您能簡單談談競爭格局嗎？

Thank you, Seamus. This is Samit. I'll take both of those questions. So for factor XIa, as we have talked about, the second Phase II study, which is in secondary stroke prevention, we expect to have the data in-house around the middle of the year. And at the appropriate conference, we will be able to share that data beyond that. And we're continuing to work with our partner, Janssen, to really execute on the future development of Milvexian.

謝謝你，西莫。這是薩米特。我將回答這兩個問題。因此，對於 XIa 因子，正如我們所討論的，第二項 II 期研究涉及中風二級預防，我們預計將在今年年中左右獲得內部數據。在適當的會議上，我們將能夠分享除此之外的數據。我們將繼續與我們的合作夥伴 Janssen 合作，真正執行 Milvexian 的未來發展。

As your question related to what the data would show and what the acceptance and availability would be and applicability would be from a bleed perspective or efficacy perspective, I think you just have to wait to see the data.

由於您的問題與數據將顯示什麼以及從出血角度或功效角度來看的接受度和可用性以及適用性有關，我認為您只需等待查看數據即可。

The primary goal for these studies is to be able to isolate what the impact is on the bleed as we look to combine it with the background therapies of anti-platelet agents as well as to then progress them further into appropriate indications, either as a single agent or as combinations. So we just have to wait for the data.

這些研究的主要目標是能夠分離出對出血的影響，因為我們希望將其與抗血小板藥物的背景療法相結合，然後將其進一步發展到適當的適應症，或者作為單一的適應症。劑或組合。所以我們只需要等待數據即可。

But as we saw in the TKR study, there was no increase in the bleeds. But we certainly saw increase as a dose -- in a dose-dependent manner from an efficacy perspective. So let's wait for the middle of the year to see the data, and then we'll define the future trajectory for the development of that.

但正如我們在 TKR 研究中看到的那樣，出血沒有增加。但我們確實看到了劑量的增加——從功效的角度來看，以劑量依賴的方式。所以我們還是等年中看數據，然後再定義未來的發展軌跡。

Coming on to the mavacamten and the competitor compound. We remain very focused and very confident in the data for mavacamten. As you know, we are launch-ready, as David spoke earlier, for the PDUFA date coming up soon. And as it relates to the additional data, we are waiting for the readout of the VALOR trial as well in the short time frame.

來到馬瓦卡姆滕和競爭對手大院。我們對 mavacamten 的數據仍然非常專注和充滿信心。如您所知，正如 David 早些時候所說，我們已做好發布準備，即將到來的 PDUFA 日期。由於它涉及到額外的數據，我們也在短時間內等待 VALOR 試驗的結果。

Now of course, we've seen the small amount of data that has been talked about from, I think, 13 patients looking now at a different cohort in combination with disopyramide. Certainly, we, in our EXPLORER trial, have looked at the commonly used background therapies of beta blockers and calcium channel blockers. In the VALOR trial, we do have patients who are going to be receiving the background therapy of disopyramide as well. So we do not see a differentiated profile at this time from a competitor perspective. We certainly are confident that we already have a Phase III trial that has been submitted and the second Phase III trial that is going to read out in the short term.

當然，現在我們已經看到了少量數據，我認為是來自 13 名患者，他們現在正在研究與丙吡胺聯合使用的不同隊列。當然，我們在 EXPLORER 試驗中研究了 β 受體阻滯劑和鈣通道阻滯劑的常用背景療法。在 VALOR 試驗中，我們確實有患者也將接受丙吡胺的背景治療。因此，從競爭對手的角度來看，我們目前沒有看到差異化的形象。我們當然有信心，我們已經提交了一項 III 期試驗，並且將在短期內宣讀第二項 III 期試驗。

The only thing I would add, Seamus, is just on mava. As we've discussed previously, the current standards of care for these patients really aren't focused on targeting the underlying nature of the disease. So we feel good about the competitive environment when we launch. And as Samit mentioned, we don't see any differentiated competition on the horizon.

Seamus，我唯一要補充的是mava。正如我們之前討論的，目前對這些患者的護理標準實際上並沒有專注於針對疾病的根本性質。因此，當我們推出時，我們對競爭環境感覺良好。正如薩米特所提到的，我們看不到任何差異化的競爭即將出現。

And certainly, based on the public data that we've seen thus far from competitors, it's entirely consistent with what would be expected from a myosin inhibitor. And so we feel very good about the competitive position for this agent and look forward to launching.

當然，根據我們迄今為止從競爭對手那裡看到的公開數據，它與肌球蛋白抑製劑的預期完全一致。因此，我們對該代理商的競爭地位感到非常滿意，並期待著推出。

We'll go to Chris Schott with JPMorgan.

我們將請摩根大通的克里斯·肖特 (Chris Schott) 發言。

Just to maybe follow up on mavacamten. Can you just help set some expectations about how we should be thinking about the launch here? I guess, is this a product, given the current standard of care, where there could be kind of a bolus of already identified patients you could go after? Or should we be thinking about maybe a more gradual ramp as you to need get -- we think about reimbursement and familiarizing physicians with whatever REMS program ends up coming out of this one?

只是為了跟進 mavacamten。您能否幫助我們設定一些關於我們應該如何考慮這裡發布的期望？我想，考慮到目前的護理標準，這是一種產品，可以對已經確定的患者進行大劑量注射嗎？或者我們是否應該考慮根據您的需要採取更漸進的方式 - 我們考慮報銷並使醫生熟悉本次 REMS 計劃最終的結果？

And then my second question was just an update on CAR T capacity. Just walk through a little bit about how you're expecting capacity to ramp as we move through 2022. And I guess when will you be in a position where capacity, I guess, is not the rate-limiting factor for the growth of these products?

然後我的第二個問題是關於 CAR T 容量的更新。只需簡單介紹一下您預計 2022 年產能將如何增長。我想您什麼時候會處於這樣的境地：產能不再是這些產品增長的限制因素？

Sure, Chris. I'll take both of those questions. With respect to mava and how we think about the shape of the opportunity, I would think about it as more of a gradual opportunity. When we look at the way this launch will likely progress, it's very much going to be in a stepwise fashion. We expect that there will be strong interest in treating the most severe patients, particularly in the centers of excellence where these patients are being treated today. That's going to be the initial focus. Beyond this, we'll expand our focus to cardiology specialists and into the broader cardiology community, where uptake is just going to be more gradual.

當然，克里斯。我將回答這兩個問題。關於 mava 以及我們如何看待機會的形式，我認為它更像是一個漸進的機會。當我們審視這次發布可能的進展方式時，它很大程度上將是逐步進行的。我們預計，人們會對治療最嚴重的患者產生濃厚的興趣，特別是在今天治療這些患者的卓越中心。這將是最初的焦點。除此之外，我們還將把重點擴大到心髒病學專家和更廣泛的心髒病學界，這些領域的採用將更加漸進。

And one other thing I would say about -- as we think about really all of these segments, we have an educational effort on that will be initiated at launch as to how physicians should initiate and treat these patients. And certainly, there will be a focused effort to get patients on therapy quickly. But just those efforts in and of themselves will take some amount of time.

我要說的另一件事是，當我們真正考慮所有這些細分市場時，我們將在啟動時啟動一項教育工作，以指導醫生應如何啟動和治療這些患者。當然，我們將集中精力讓患者快速接受治療。但僅這些努力本身就需要一些時間。

The good news is we have a very strong team with an established presence in this space. We have a very good drug. So we feel very good about the long-term potential for the asset. And that stepwise approach that I articulated really is in line with the overall opportunity of $4-plus billion that we see for this asset.

好消息是我們擁有一支非常強大的團隊，在這個領域擁有穩固的地位。我們有一種非常好的藥物。因此，我們對該資產的長期潛力感到非常滿意。我所闡述的逐步方法確實符合我們對該資產所看到的 4 億美元以上的總體機會。

Moving to cell therapy supply constraints. As we've said previously, the supply constraints that we're seeing right now are mainly related to Abecma. And our efforts are really focused on working with CMOs to accelerate capacity for vector. And then internally, we're focused on flat capacity. And there are a number of things across both of these efforts that we're focused on, including training and qualifying new staff, increasing our operational efficiency and increasing site capacity.

轉向細胞治療供應限制。正如我們之前所說，我們現在看到的供應限制主要與 Abecma 有關。我們的努力真正集中在與 CMO 合作，以提高載體的產能。然後在內部，我們專注於固定容量。我們重點關注這兩項工作中的許多事情，包括培訓新員工並使其合格，提高我們的運營效率並增加站點容量。

On Abecma, we would anticipate being in a much better position for supply as we get into the middle of this year.

對於 Abecma，我們預計，進入今年年中時，供應狀況會更好。

And then as it relates to Breyanzi, Breyanzi, the big focus there is on vector supply. It's something we continue to stay focused on. And we fully -- we expect to be in a position to support demand as we get later into this year and certainly by the time that we would have any label expansions for that product.

然後，當它與 Breyanzi、Breyanzi 相關時，重點是載體供應。這是我們繼續關注的事情。我們完全希望在今年晚些時候以及我們對該產品進行任何標籤擴展時能夠滿足需求。

So next, we'll go to Geoff Meacham with Bank of America.

接下來，我們將請到美國銀行的傑夫·米查姆 (Geoff Meacham)。

For some of the new launches, are there any metrics you guys can provide that show the wins in access and reimbursement? Mostly talking about cell therapies and Zeposia.

對於一些新推出的產品，你們可以提供任何指標來顯示在訪問和報銷方面的勝利嗎？主要談論細胞療法和 Zeposia。

The bigger picture, is just trying to assess the tipping point for this year potentially for the launches collectively versus what we saw last year, which was a lot of lumpiness on a kind of a sequential basis.

更大的前景只是試圖評估今年可能集體發布的臨界點與我們去年看到的情況相比，去年在連續的基礎上有很多波動。

And then the second question real quick on deucravacitinib. I know there's been a lot of angst about the potential for differentiating labels versus JAKs. I just want -- now that we have clarity on the latter, just wanted to get maybe an updated view from you guys on that.

然後第二個問題是關於 deucravacitinib 的。我知道人們對於區分唱片公司和 JAK 的潛力存在很多擔憂。我只是想——現在我們已經清楚了後者，只是想從你們那裡得到對此的最新看法。

Sure. Maybe I'll start, Geoff. Thanks for the question. So as we look at access really across all of these launches, we feel very good about where we are from an access standpoint.

當然。也許我會開始，傑夫。謝謝你的提問。因此，當我們真正審視所有這些發布的訪問時，從訪問的角度來看，我們對自己所處的位置感到非常滿意。

And I'll start with cell therapy. Cell therapy actually, I think, is a very, very good story. We've seen no issues with respect to access constraints for our cell therapy launches. We've discussed the supply constraints. But the launches have gone off really without a hitch from a supply -- from an access standpoint. And in fact, if you look at the class of agents more generally, if you go back a couple of years, as you well know, access and reimbursement were significant areas of concerns. And I would say largely for the class of agents, we've been trending in the right direction. But we see no issues on our cell therapy assets.

我將從細胞療法開始。我認為細胞療法實際上是一個非常非常好的故事。我們沒有發現細胞治療產品的准入限制存在任何問題。我們已經討論了供應限制。但從訪問的角度來看，這些產品的發布確實沒有受到供應的影響。事實上，如果你更廣泛地審視代理人的類別，如果你回到幾年前，正如你所知，訪問和報銷是重要的關注領域。我想說的是，對於代理類別來說，我們一直在朝著正確的方向發展。但我們認為我們的細胞治療資產沒有任何問題。

As we switch gears and you mentioned Zeposia, obviously, the focus is on UC. But very quickly on MS, I feel very good about the access position there. We have very broad coverage in MS, so really not a significant concern on the MS side.

當我們切換方向時，您提到了 Zeposia，顯然，重點是 UC。但很快在 MS 上，我對那裡的訪問位置感覺非常好。我們在 MS 方面的覆蓋範圍非常廣泛，因此 MS 方面確實不是一個重大問題。

In UC, we've been very clear that we have to execute a diligent effort around access over the course of this year. What I can say coming into 2022 is we have very broad formulary coverage for Zeposia. Now how restrictive that formulary coverage is, it varies by plan. And for the course of this year, for those patients with less restricted access, the focus is going to be on converting those patients from starter or bridge programs to commercial drug, and do so very quickly. For patients with more restricted access, which unsurprisingly for our first full year in the market, most patients have multiple step edits, the focus is going to be on working through those restrictions, and that's going to take more time.

在加州大學，我們非常明確地表示，今年我們必須圍繞訪問做出不懈努力。我可以說，進入 2022 年，我們的 Zeposia 處方覆蓋範圍非常廣泛。現在，處方保險範圍有多麼嚴格，因計劃而異。今年，對於那些獲得較少限制的患者，重點將是將這些患者從起始或過渡方案轉變為商業藥物，並且要非常快地做到這一點。對於訪問受到更多限制的患者來說，這並不奇怪，這是我們進入市場的第一個全年，大多數患者都需要進行多個步驟編輯，重點將是解決這些限制，這將需要更多時間。

What I can say, though, in any case, is that on Zeposia, we're continuing to build volume over the course of this year. The plan has been and continues to be to then leverage that volume to move Zeposia into an earlier access position as we head into 2023, and we're very much on track to do that.

但無論如何，我可以說的是，在 Zeposia 上，我們今年將繼續增加銷量。該計劃一直並將繼續是在進入 2023 年時利用這一數量將 Zeposia 推向更早的訪問位置，而且我們非常有望做到這一點。

And Geoff, I'll take on the question around deucravacitinib. So let me start by saying that we are obviously not going to speculate on the label for what we will see. But we certainly remain very confident in the efficacy and the safety profile that we've talked about before. And we are looking forward to the PDUFA date in September.

傑夫，我將回答有關 deucravacitinib 的問題。首先我要說的是，我們顯然不會根據標籤推測我們將看到什麼。但我們當然對我們之前討論過的功效和安全性仍然非常有信心。我們期待 9 月份的 PDUFA 日期。

Next, we'll go to Steve Scala with Cowen.

接下來，我們將與 Cowen 一起討論 Steve Scala。

I have a couple of questions. Opdivo was a bit weak in Q4, similar to what we've seen from some of your competitors. Diagnoses still appear to be pressured despite fewer COVID-related shutdowns. Are there any other reasons for weak oncology numbers? And what is the outlook for recovery? So that's the first question.

我有一些問題。 Opdivo 在第四季度有點疲軟，類似於我們從一些競爭對手那裡看到的情況。儘管與新冠病毒相關的停工次數有所減少，但診斷似乎仍然面臨壓力。腫瘤學數據疲弱還有其他原因嗎？復甦的前景如何？這是第一個問題。

The second question is for Samit. Samit, do you or anyone else at Bristol know the total number of stroke and bleeding events in the Milvexian stroke study to date. So both arms combined, not each one. And if yes, how are those total stroke and bleeding events trending to what you expected?

第二個問題是問薩米特的。 Samit，您或布里斯托爾的其他人知道迄今為止 Milvexian 中風研究中中風和出血事件的總數嗎？所以兩隻手臂結合在一起，而不是各自一隻。如果是，那麼中風和出血事件總數的趨勢如何符合您的預期？

Maybe I'll start, Steve. With respect to -- let me just say at the outset, with respect to Opdivo, we're actually very happy with the performance we saw for Opdivo in the quarter. As David and Giovanni mentioned, we saw a return to growth for Opdivo and actually saw an acceleration of Opdivo in the latter half of the year.

也許我會開始，史蒂夫。首先，我要說的是，關於 Opdivo，我們實際上對 Opdivo 在本季度看到的表現非常滿意。正如 David 和 Giovanni 提到的，我們看到 Opdivo 恢復增長，並且實際上看到 Opdivo 在下半年加速增長。

As it relates to COVID, we have generally seen some improvement in a number of markets. But as you would imagine, the situation remains quite dynamic. As it relates to I-O specifically, new patient volume has been gradually recovering. Though I would say, where we sit today, we're roughly 5% to 10% below pre-COVID levels in terms of patient volume. There's just a considerable amount of variability across tumor types as well as in academic versus community. But on net, it's about 5% to 10% below where we were pre-COVID.

由於與新冠疫情相關，我們普遍看到許多市場有所改善。但正如你所想像的那樣，情況仍然相當動態。由於與 I-O 特別相關，新患者數量已逐漸恢復。不過我想說的是，就患者數量而言，我們今天的情況比新冠疫情前的水平大約低 5% 到 10%。不同腫瘤類型以及學術界與社區之間存在相當大的差異。但從網上來看，這一數字比新冠疫情爆發前的水平低了約 5% 到 10%。

Our hope in terms of the outlook is that we'll continue to see an improvement over the course of the year. If the pandemic has taught us anything, it's that we're going to have to continue to be flexible and agile.

我們對前景的希望是，我們將在這一年中繼續看到改善。如果說這場大流行教會了我們什麼的話，那就是我們必須繼續保持靈活性和敏捷性。

What I can say definitively is that the impact will likely vary by product and market. From our standpoint, I think we've shown our business is resilient, and our ability to really through the pandemic. And I think we've demonstrated an ability to execute. But sort of if you level it [up], it's still a dynamic situation, and one we'll watch carefully.

我可以肯定地說，影響可能會因產品和市場而異。從我們的角度來看，我認為我們已經表明我們的業務具有彈性，並且我們有能力真正度過這一流行病。我認為我們已經展示了執行能力。但如果你升級它，它仍然是一個動態的情況，我們會仔細觀察。

And on the Milvexian trial, Steve. The study is ongoing, and we will not be talking about data, whether it's a pooled analysis or unblinded. We'll just have to wait for the data. And as I said earlier, we will be presenting the data at the appropriate conference. Really looking forward to it though.

在米爾維西安審判中，史蒂夫。這項研究正在進行中，我們不會談論數據，無論是匯總分析還是非盲分析。我們只需要等待數據即可。正如我之前所說，我們將在適當的會議上展示這些數據。不過真的很期待。

So next, we'll go to Chris Shibutani with Goldman Sachs.

接下來，我們將採訪高盛的 Chris Shibutani。

If I could ask a question about the immuno-oncology franchise, maybe more medium to longer term. There's a couple of dynamics that are happening. One, I think we have a PDUFA coming up in March for the LAG-3 combination fixed dose. Anything that you could share in terms of how you're thinking about positioning this so that you have success commercially, given the anticipation for competition, not just from other players, but also from other regimens, like TIGIT?

如果我可以問一個有關免疫腫瘤學專營權的問題，也許是中長期的問題。有一些動態正在發生。第一，我認為我們將在 3 月份推出針對 LAG-3 組合固定劑量的 PDUFA。考慮到競爭的預期，您是否可以分享一下您如何考慮定位這一點，以便您在商業上取得成功，不僅來自其他玩家，還來自其他療法，如 TIGIT？

Could you also comment, with a combination of data from bempeg plus Opdivo, which I believe could be in the second quarter time frame. The economics are distinct there. However, help us at all with progress and time lines, that would be appreciated.

您能否結合 bempeg 和 Opdivo 的數據發表評論，我相信這可能是在第二季度的時間範圍內。那裡的經濟學是獨特的。但是，如果您能在進度和時間表方面為我們提供幫助，我們將不勝感激。

And then finally, on the I-O, we see potential for the entry of lower-cost checkpoint inhibitors, [PD-1s]. Can you share with us your initial thoughts at this stage about how you see that influencing the market dynamics for checkpoint inhibitors and I-O?

最後，在 I-O 上，我們看到了低成本檢查點抑製劑 [PD-1] 進入市場的潛力。您能否與我們分享您現階段的初步想法，即您如何看待這對檢查點抑製劑和 I-O 市場動態的影響？

Sure. Maybe I'll start and I'll hit your first and third question. We're very pleased with the opportunity to potentially launch relatlimab. As we've said, if you look at the first-line metastatic melanoma market, it's really divided into thirds. You've got 1/3 of patients who are treated with dual I-O, that's Opdivo plus Yervoy. that's a very strong position, given the sustained OS benefit that we have with that population.

當然。也許我會開始回答你的第一個問題和第三個問題。我們對有機會推出 relatlimab 感到非常高興。正如我們所說，如果你看看一線轉移性黑色素瘤市場，你會發現它實際上分為三部分。 1/3 的患者接受雙 I-O 治療，即 Opdivo 加 Yervoy。考慮到我們在這些人群中獲得的持續操作系統優勢，這是一個非常有利的地位。

You have about 1/3 of patients who are treated with I-O monotherapy, roughly split between Opdivo and KEYTRUDA 50-50. And then you have 1/3 of the market which is really focused on targeted therapies.

大約有 1/3 的患者接受 I-O 單藥治療，其中 Opdivo 和 KEYTRUDA 大致各佔 50-50。然後你有 1/3 的市場真正專注於靶向治療。

We see the opportunity for relatlimab to really go after that 1/3 of the market, which is single agent PD-1 therapy. We think that the data are very compelling relative to that population. Remember that relatlimab is 2 products in 1 vial. And so we think the opportunity to offer those patients dual I-O therapy in a fixed-dose combination offers a significant improvement over single-agent monotherapy, and that's going to be the initial focus at launch.

我們看到 relatlimab 有機會真正爭奪那 1/3 的市場，即單藥 PD-1 療法。我們認為，相對於該人群，這些數據非常引人注目。請記住，relatlimab 是 1 瓶 2 種產品。因此，我們認為為這些患者提供固定劑量組合的雙重 I-O 治療的機會比單藥單一治療有顯著改善，這將是啟動時的最初重點。

As it relates to your question on low-cost entries of PD-1 agents. We don't see a significant threat to our business in the near to medium term from these products. We -- in our larger markets, like the U.S., evidence continues to be the most important dimension of choice. Physicians want to see data in a specific tumor and patient type. And so there may be markets where these sort of low-cost me-too drugs are able to piggyback on innovation and drive use, but those historically have not been our larger markets.

因為這涉及到你關於 PD-1 藥物低成本進入的問題。我們認為這些產品在中短期內不會對我們的業務構成重大威脅。我們——在美國等更大的市場中，證據仍然是最重要的選擇維度。醫生希望查看特定腫瘤和患者類型的數據。因此，可能存在一些市場，這些低成本仿製藥能夠借助創新並推動使用，但這些市場在歷史上並不是我們更大的市場。

Obviously, things can evolve and we'll continue to monitor and adjust as necessary. But I think as a sort of put a finer point on it, we shouldn't underestimate the barriers to sort of broad-based commoditization in oncology, particularly for a product like Opdivo, given the breadth of our data and indications.

顯然，事情可能會發生變化，我們將繼續進行監控並根據需要進行調整。但我認為，從某種角度來說，考慮到我們數據和適應症的廣度，我們不應該低估腫瘤學領域廣泛商品化的障礙，特別是像 Opdivo 這樣的產品。

And Chris, on the bempeg side, just as a reminder, there are 3 readouts that we anticipate this year, 1 in melanoma, 1 in renal cancer and 1 in bladder cancer. The first of it, as you very well pointed out, is in melanoma. We are anticipating the data within the first half of this year.

Chris，在 bempeg 方面，提醒一下，我們預計今年會有 3 個讀數，1 個是黑色素瘤，1 個是腎癌，1 個是膀胱癌。正如您所指出的，第一個是黑色素瘤。我們預計今年上半年的數據。

With that said, we are certainly very pleased to have 3 I-O mechanism already, as an PD-1 as well as CTLA-4. And then anticipating the PDUFA and launch for relatlimab, as you also mentioned earlier. And we're looking forward to continuing work with Nektar in progressing the program as the data continues to evolve.

話雖如此，我們當然非常高興已經擁有 3 個 I-O 機制，即 PD-1 和 CTLA-4。然後，正如您之前提到的，預計 PDUFA 和 relatlimab 的啟動。隨著數據的不斷發展，我們期待繼續與 Nektar 合作推進該計劃。

Next, we'll go to Tim Anderson with Wolfe Research.

接下來，我們將前往沃爾夫研究中心的蒂姆·安德森 (Tim Anderson)。

This is [Adam] on behalf of Tim. On mavacamten, you've described this as being a $4 billion-plus product by 2029. It seems that there are 2 main drivers of this. One of which is that the forecast assumes a tripling of diagnosis rates for OHCM, going from about 25% today to 75% in the future. And the second is the mention of NHCM and other indications.

我是[亞當]代表蒂姆。在 mavacamten 上，您將其描述為到 2029 年將成為價值超過 40 億美元的產品。這似乎有兩個主要驅動因素。其中之一是，預測假設 OHCM 的診斷率將增加兩倍，從目前的約 25% 增加到未來的 75%。其次是提到了NHCM和其他適應症。

My question is twofold. How realistic is it to expect a tripling of diagnosis rates?

我的問題是雙重的。預期診斷率增加兩倍有多現實？

And second, what portion of the $4 billion is due to NHCM and other indications that you have not talked about as much?

其次，這 40 億美元中哪一部分是由於 NHCM 和您沒有談論太多的其他跡象？

Separately, can we assume that an FDA Advisory Committee meeting is unlikely with this drug before approval happens?

另外，我們是否可以假設在批准之前不太可能召開 FDA 諮詢委員會會議來討論這種藥物？

Sure. Maybe I'll take both of those questions, and then -- or at least the first 2 questions.

當然。也許我會回答這兩個問題，然後——或者至少回答前兩個問題。

So Adam, with respect to how we thought about mava, first of all, this is a market where we see a fairly well-defined patient population. There are about 80,000 to 100,000 patients in the U.S. and roughly a comparable number ex U.S. We see significant unmet need for this patient population. And the initial focus at launch is going to be focused on treating those patients who are symptomatic, diagnosed, and where there's a real urgency to treat.

Adam，關於我們對 mava 的看法，首先，這是一個我們看到相當明確的患者群體的市場。美國約有 80,000 至 100,000 名患者，美國以外的患者數量大致相當。我們發現該患者群體的需求未得到滿足。啟動時的最初重點將集中於治療那些有症狀、已確診且確實需要緊急治療的患者。

Now what we have said is that, over the longer term with obstructive HCM, the focus will be on increasing the diagnosis rate. What we have said is that we plan on, where we think it's feasible, to double that diagnosis rate. It is currently, as you note, about 25%. And we think, with significant efforts, which we certainly have the skill set in the field to do, we think we can double that over time. So that's how we're looking at it.

現在我們所說的是，從長遠來看，阻塞性 HCM 的重點將是提高診斷率。我們所說的是，我們計劃在我們認為可行的情況下將診斷率提高一倍。正如您所注意到的，目前這一比例約為 25%。我們認為，通過巨大的努力，我們當然擁有該領域的技能，我們認為隨著時間的推移，我們可以將這一數字加倍。這就是我們的看法。

And in terms of the overall opportunity, the majority of the opportunity that we see is in obstructive disease. But certainly, we are looking forward to potentially seeing data in nonobstructive as well.

就總體機會而言，我們看到的大部分機會是在阻塞性疾病領域。但當然，我們也期待著有可能看到無阻礙的數據。

Yes. And on the ADCOM question, Adam, we have not been notified for a potential ADCOM. We do believe in the strong profile of mavacamten and benefit it provides in patients that we have enrolled in clinical trials for obstructive hypertrophic cardiomyopathy. And we are now looking to launch, as you know, in April of 2022, as Chris said.

是的。關於 ADCOM 問題，Adam，我們尚未收到有關潛在 ADCOM 的通知。我們確實相信 mavacamten 的強大功效及其為我們已參加梗阻性肥厚型心肌病臨床試驗的患者帶來的益處。正如克里斯所說，我們現在計劃於 2022 年 4 月推出。

Next, we'll go to Andrew Baum with Citi.

接下來，我們將前往花旗銀行的安德魯·鮑姆 (Andrew Baum)。

A couple of questions. So first on Milvexian. I'm mindful of the dose-dependent interaction of aspirin with Plavix. You have a number of trials ongoing and completed looking at potential drug interactions with Milvexian. Perhaps you could comment on level of reassurance in terms of either interaction with anti-platelets or commonly administered drugs in this patient population.

有幾個問題。首先是米爾維西安。我注意到阿司匹林與波立維之間的劑量依賴性相互作用。您正在進行並已完成多項試驗，研究與 Milvexian 潛在的藥物相互作用。也許您可以評論一下該患者群體中與抗血小板藥物或常用藥物相互作用的保證程度。

And then second, you've already highlighted the Q1 -- inflation in 2021 for Eliquis. Perhaps you could talk more generally to the trends, particularly for U.S. Eliquis growth for 2022. I seem to remember that you've been excluded from 1 of the big 3 formularies. I'm assuming that pricing will offset volume. But if you can talk to what we expect for this year, and that would be helpful.

其次，您已經強調了 Eliquis 2021 年第一季度的通貨膨脹。也許您可以更籠統地談談趨勢，特別是 2022 年美國 Eliquis 的增長。我似乎記得您已被排除在 3 大處方集之一之外。我假設定價將抵消銷量。但如果您能談談我們對今年的期望，那就會有所幫助。

So I will start off, Andrew. Thank you for your questions. And for Milvexian, as you know, that we have, first of all, the study ongoing already with anti-platelet agents in the SSP, so we'll get to see that data when that reads out.

那麼我就開始吧，安德魯。謝謝您的提問。對於 Milvexian 來說，正如你所知，我們首先已經在 SSP 中進行抗血小板藥物的研究，所以當數據讀出時我們將看到這些數據。

In terms of the other drug-drug interaction studies, that is part and parcel of usual clinical pharmacology package that we prepare in anticipation of future filings and NDA. At the current time, we do not see any major impact or anything major in terms of BDI.

就其他藥物相互作用研究而言，這是我們為未來的申請和 NDA 準備的常規臨床藥理學包的重要組成部分。目前，我們沒有看到任何重大影響或 BDI 方面的任何重大影響。

Yes. On the Eliquis questions, first of all, we're very happy with the performance that we saw with Eliquis, obviously, coming out of the fourth quarter. And then this year, we expect continued strong growth for Eliquis. Eliquis is going to likely going to be the key driver of the overall OAC market. We're seeing a nice delta in share between our new-to-brand share and total brand share, which is roughly around 7% now. That gives us confidence in the near-term growth trajectory. And we really do expect to see Eliquis NBRx and TRx share growth this year, both at the expense of warfarin and Xarelto.

是的。關於 Eliquis 問題，首先，我們對 Eliquis 在第四季度的表現非常滿意。今年，我們預計 Eliquis 將繼續強勁增長。 Eliquis 很可能成為整個 OAC 市場的主要驅動力。我們發現新品牌份額與總品牌份額之間存在很大的差異，目前約為 7% 左右。這讓我們對近期增長軌跡充滿信心。我們確實預計今年 Eliquis NBRx 和 TRx 的份額會增長，但華法林和 Xarelto 的份額都會有所下降。

As it relates to the [zinc] situation, we see no meaningful impact on revenue. There are a few things to consider here. First, it's a relatively small part of our overall business. You certainly won't lose all of the volume. What we know in this space is that there's significant risk for nonmedical switching of patients who are on Eliquis. We know also that downstream accounts, in light of that, many of them will not adhere to the change that's been proposed at a macro level. And so we're actually very confident that the impact of revenue will be nonmaterial, if any.

由於它與[鋅]情況有關，我們認為對收入沒有重大影響。這裡有一些事情需要考慮。首先，它只占我們整體業務的一小部分。您當然不會失去所有音量。我們在這個領域所知道的是，使用 Eliquis 的患者進行非醫療轉換存在很大的風險。我們還知道，鑑於此，下游賬戶中的許多人不會遵守宏觀層面提出的變革。因此，我們實際上非常有信心，收入的影響將是非實質性的（如果有的話）。

And the last thing I would say just related to that situation is we've said consistently that we're going to continue to be disciplined on gross to nets and how we manage those, and this is part of that story.

我要說的與這種情況相關的最後一件事是，我們一直表示，我們將繼續在總進球數以及我們如何管理這些方面受到紀律處分，這是故事的一部分。

Next, we'll go to Ronny Gal with Bernstein.

接下來，我們將和伯恩斯坦一起去羅尼·加爾。

First, just following up on Andrew's question. Can you talk a little bit about the benefit from 340 switch, especially from Eliquis? It seems to -- the net prices, Eliquis and 340B was close to nothing. And given the volume estimates that we are seeing, it should be a pretty good benefit for them this year. Can you talk about that?

首先，跟進安德魯的問題。您能談談 340 switch、尤其是 Eliquis 的好處嗎？ Eliquis 和 340B 的淨價似乎幾乎為零。考慮到我們所看到的數量估計，今年對他們來說應該是一個相當不錯的收益。你能談談嗎？

And second, Orencia. It seems to be growing together with the RA market. It seems to be in a position to grow better, given the JAK inhibitor safety issues. Can you talk a little bit about what you're seeing and what's your projection for 2022?

第二個，奧倫西亞。它似乎與 RA 市場一起成長。考慮到 JAK 抑製劑的安全問題，它似乎能夠發展得更好。您能談談您所看到的情況以及您對 2022 年的預測嗎？

Sure. Let me -- Giovanni, do you want to start?

當然。讓我——喬瓦尼，你想開始嗎？

Go ahead, Chris.

繼續吧，克里斯。

Sure. So on 340B, let me just say, at a macro level, we remain committed to ensuring the eligibility of patients for 340B, those patients who can directly benefit from the program. And what I would say, there's really no change in our stance with respect to 340B as it relates to the program. We're committed to it, and we're committed to patients maintaining access to our medicine.

當然。所以關於340B，我只想說，在宏觀層面上，我們仍然致力於確保患者有資格參加340B，即那些可以直接從該計劃中受益的患者。我想說的是，我們對 340B 的立場確實沒有改變，因為它與該計劃有關。我們致力於此，並致力於讓患者能夠繼續獲得我們的藥物。

The change that we announced really was reflective of 2 things: First, BMS and Celgene having different policies around the recognition of contract pharmacies and needing to align those as part of integration; and then second, wanting to ensure that the 340B discounts that we pay are valid and appropriate, and we feel this change in policy allows us to do that. And so that's really been the focus for how we think about the 340B program.

我們宣布的變化實際上反映了兩件事：首先，BMS 和 Celgene 在認可合同藥房方面有不同的政策，需要在整合過程中調整這些政策；其次，希望確保我們支付的 340B 折扣是有效且適當的，我們認為政策的這一變化使我們能夠做到這一點。因此，這確實是我們思考 340B 計劃的重點。

And then do you mind repeating your second question again?

那麼你介意再重複一遍你的第二個問題嗎？

It would be great if you can quantify -- hello? It will be great if you can quantify the 340B impact.

如果你能量化那就太好了——你好？如果您能夠量化 340B 的影響，那就太好了。

And the second question was around Orencia trends and the potential to benefit from the JAK inhibitors black box label.

第二個問題是關於 Orencia 的趨勢以及從 JAK 抑製劑黑盒標籤中受益的潛力。

Sure. We're not going to comment on any impact of 340B. Again, I think we've given the rationale for having made that change.

當然。我們不會評論 340B 的任何影響。我再次強調，我們已經給出了做出這一改變的理由。

As it relates to Orencia, look, Orencia continues to perform well in the RA market. The way we've thought about any potential change from a label update on JAK as it relates to Orencia or, frankly, any of our products, is that those changes will likely continue to push JAKs into later lines of therapy as they are -- as labels are updated and their position continues to evolve. So we think there's potentially opportunity.

與 Orencia 相關的是，Orencia 在 RA 市場上繼續表現良好。我們考慮 JAK 標籤更新帶來的任何潛在變化的方式，因為它與 Orencia 或坦率地說，與我們的任何產品相關，這些變化可能會繼續將 JAK 推入以後的治療系列，因為它們是——隨著標籤的更新及其地位的不斷發展。所以我們認為存在潛在的機會。

That said, I think our focus on, really, all of our products continues to execute against the strategy that we have, for those assets to continue to compete effectively in those markets. And obviously, we'll allow the situation with JAKs to evolve as they do.

也就是說，我認為我們對所有產品的關注實際上都繼續按照我們現有的戰略執行，以便這些資產繼續在這些市場中有效競爭。顯然，我們將允許 JAK 的情況隨著他們的發展而發展。

Next, we'll go to Luisa Hector with Berenberg.

接下來，我們將和貝倫貝格一起去路易莎·赫克托。

Just wanted to discuss a little bit more on the '22 outlook and the impact of Revlimid. So I just wondered if there are any particular risks you would highlight around the delivery of your sales target. Anything, just anything of note. And I guess really to confirm the pace of the Revlimid erosion is pretty predictable, so just checking on levels of uncertainty.

只是想更多地討論 '22 的前景和 Revlimid 的影響。所以我只是想知道在實現銷售目標方面您是否會強調任何特定的風險。任何事情，只是任何值得注意的事情。我想確實要確認來那度胺侵蝕的速度是可以預測的，所以只需檢查不確定性水平即可。

And then specifically around how you are adapting to Revlimid generic entry in terms of your cost base. Any color around that, given that you have the ongoing presence in multiple myeloma. So just trying to understand kind of the cost side of it.

然後具體圍繞您如何根據成本基礎適應來那度胺仿製藥。考慮到您持續存在多發性骨髓瘤，周圍的任何顏色。所以只是想了解它的成本方面。

Yes. thanks for the question, Luisa. As we think about Revlimid, we thought it was important this year, #1, to provide guidance on the full year. And secondly, we thought it was really important to provide guidance on the quarter. And I'd say one thing is that these are -- the contracts are annual volume limitations. So as the generics enter, it's all -- there could be quarter-to-quarter variability based upon how quickly the product makes it to the marketplace. So that's why we thought it was important to provide that.

是的。謝謝你的提問，路易莎。當我們考慮來那度胺時，我們認為今年很重要，#1，為全年提供指導。其次，我們認為提供本季度的指導非常重要。我想說的一件事是，這些合同是年度數量限制。因此，隨著仿製藥的進入，根據產品進入市場的速度，可能會出現季度與季度的變化。這就是為什麼我們認為提供這一點很重要。

The first generic entry is occurring in March, so there could be variability between the first and second quarter. And then the rest -- remainder of the generics will come usually about 180 days later, it's pretty typical in a generic entry scenario, so that would be in the September time frame. But for the full year, we feel very confident in the guidance that we provided for the full year as it relates to Revlimid.

第一個通用條目發生在三月份，因此第一季度和第二季度之間可能存在差異。然後剩下的——其餘的仿製藥通常會在大約 180 天后上市，這在仿製藥進入場景中非常典型，所以那將是在 9 月份的時間範圍內。但對於全年而言，我們對我們為全年提供的與來那度胺相關的指導非常有信心。

As far as the expense base is concerned, I mean, this is a really fortunate thing for us. And the standpoint is, if you think about the 9 products that we're bringing to the marketplace, the 6 that are on the market and the 3 that we're launching this year, we're able to move resources within our therapeutic areas and reallocate the resources to the launch brands. So as you think about our hematology sales force, being able to move those resources out of Revlimid and into like cell therapy with the Breyanzi and Abecma, we're able to use existing resources to support this launch brands and maintain our cost base where we are. So -- and that's why we provided the guidance on operating expenses as we did.

就費用基礎而言，我的意思是，這對我們來說確實是一件幸運的事情。我們的觀點是，如果你考慮一下我們將推向市場的 9 種產品、已上市的 6 種產品以及我們今年推出的 3 種產品，我們能夠在我們的治療領域內轉移資源並將資源重新分配給啟動品牌。因此，當您想到我們的血液學銷售隊伍時，能夠將這些資源從 Revlimid 轉移到 Breyanzi 和 Abecma 等細胞療法中，我們就能夠利用現有資源來支持該推出品牌並維持我們的成本基礎是。因此，這就是我們提供運營費用指導的原因。

Luisa, this is Giovanni. Let me just make another comment there. You mentioned about our level of confidence. David referenced Revlimid. Let me just say this is an important year for us because, obviously, it's the first year in which there will be generics of Revlimid. And what I'm really pleased of is the fact that we've got strong momentum with in-line business. We are making great progress with the launch brands that are already on the market. We're looking forward to 3 important approvals.

路易莎，這是喬瓦尼。讓我再發表一下評論。您提到了我們的信心程度。大衛提到了 Revlimid。我只想說，今年對我們來說是重要的一年，因為顯然，這是來那度胺仿製藥的第一年。我真正感到高興的是，我們的在線業務勢頭強勁。我們在市場上推出的品牌方面取得了巨大進展。我們期待獲得 3 項重要批准。

And this year, as you know, we've guided to growth, both in terms of our revenue base, but also in terms of earnings per share. So I think that's a clear demonstration that we are confident in the ability to grow though the loss of exclusivity of Revlimid this year and over the next few years, just because of the strength and resilience of the underlying business and the fact that we are accelerating the transition of our portfolio into new brands.

正如您所知，今年我們在收入基礎和每股收益方面都實現了增長。因此，我認為這清楚地表明，我們對在今年和未來幾年失去 Revlimid 獨家經營權的情況下實現增長充滿信心，因為基礎業務的實力和彈性以及我們正在加速的事實我們的產品組合轉變為新品牌。

Next, we'll go to Evan Seigerman with BMO.

接下來，我們將拜訪 BMO 的 Evan Seigerman。

I'd like to dive a little bit more on the investigational CELMoDs, understanding Revlimid's going on generic. What do you need to show with these clinical trials to help maybe replace Revlimid and pomalidomide in the treatment landscape?

我想更深入地研究 CELMoD，了解 Revlimid 的通用性。您需要通過這些臨床試驗展示什麼來幫助替代來那度胺和泊馬度胺在治療領域的應用？

And kind of how do you think about progressing those in clinical trials? Understanding that you have the standard of care with your current assets.

您如何看待在臨床試驗中取得進展？了解您對當前資產的管理標準。

Sure. Thank you, Evan, for the question. From a CELMoD perspective, the way we are thinking about development, and as we continue forward, we've generated the data in the late lines looking at the combination of iberdomide plus dexamethasone and CC-480 plus dexamethasone. And we have early data in triplets as well looking at combinations with VELCADE, dexamethasone as well as CD38 antibodies and dexamethasone, et cetera.

當然。謝謝你，埃文，提出這個問題。從 CELMoD 的角度來看，我們考慮開發的方式，並且隨著我們繼續前進，我們在後期生成了有關伊伯多胺加地塞米松和 CC-480 加地塞米松組合的數據。我們有三聯體的早期數據，以及與 VELCADE、地塞米松以及 CD38 抗體和地塞米松等的組合。

As you will see later this year, we are initiating a Phase III trial of iberdomide plus VELCADE plus dexamethasone, comparing to -- sorry, iberdomide, daratumumab, dexamethasone comparing to dexamethasone; as well as VELCADE and CD38 antibody. So that's the first foray into the second-line plus patient population for the CELMoD.

正如您將在今年晚些時候看到的，我們正在啟動伊伯多胺加 VELCADE 加地塞米鬆的 III 期試驗，比較——抱歉，伊伯多胺、達雷木單抗、地塞米鬆與地塞米松進行比較；以及 VELCADE 和 CD38 抗體。這是 CELMoD 首次涉足二線及以上患者群體。

The other trials that you will see in the short while coming up will be the Phase III trials of CC-480 looking to replace pomalidomide, and that would be a head-to-head comparison versus pomalidomide combinations.

您很快就會看到的其他試驗將是 CC-480 的 III 期試驗，旨在取代泊馬度胺，這將是與泊馬度胺組合的頭對頭比較。

And in 2022 -- sorry, 2023 and beyond, you will see trials of iberdomide looking into the post-transplant maintenance head-to-head comparison versus Revlimid; as well as the newly diagnosed patients who are transplant-non-eligible, to again, replace Revlimid in the first line or front setting.

到 2022 年——抱歉，2023 年及以後，您將看到伊伯多胺與來那度胺 (Revlimid) 進行移植後維護的試驗；以及新診斷的不符合移植資格的患者，再次在一線或前線取代 Revlimid。

Those are the ways we are thinking about as we think about replacement of the current image. But let me also ask Chris to comment on the commercial perspective.

這些是我們在考慮替換當前圖像時正在考慮的方式。但我也請克里斯從商業角度發表評論。

Yes, I think you've covered most of it, Samit. It's going to be important, as Samit noted, to generate data that differentiates directly from the IMiDs. There's obviously going to be a focus to address areas of IMiD unmet need, whether it's renal impairment or a look at potentially other populations where IMiDs underperformed. And then ultimately, from a commercial standpoint, we're going to need to establish a strong value proposition versus generic, but all of that will be part of the plan.

是的，我想你已經涵蓋了大部分內容，薩米特。正如 Samit 指出的那樣，生成直接區別於 IMiD 的數據非常重要。顯然，我們將重點解決 IMiD 未滿足需求的領域，無論是腎功能損害還是 IMiD 表現不佳的潛在其他人群。最終，從商業角度來看，我們需要建立一個與仿製藥相比強大的價值主張，但所有這些都將成為計劃的一部分。

Next, we'll go to Carter Gould with Barclays.

接下來，我們將與巴克萊銀行一起拜訪卡特·古爾德。

I wanted to focus a little bit on the GI immunology portfolio. Last year, after the Phase II UC data sort of was disappointing, you guys talked about an additional study in UC. That's no longer sort of on your slide in terms of catalysts for '23 and -- '22 and '23. Are -- just any additional thoughts on that front and how you think about sort of being able to revisit UC? And if we'll be able to get an answer to that question here in '22.

我想稍微關註一下胃腸道免疫學組合。去年，在 UC II 期數據有點令人失望之後，你們談到了 UC 的另一項研究。就“23”以及“22”和“23”的催化劑而言，這不再是你幻燈片上的內容。在這方面您還有什麼其他想法嗎？您對重新訪問加州大學有何看法？如果我們能夠在 22 年在這裡得到這個問題的答案。

And then maybe a little bit off the radar, cendakimab. We seem to sort of expand the development program there and then recently add sort of a Phase III study in Japan, so in eosinophilic gastroenteritis. Wanted to see if there were broader plans to run a pivotal study in the U.S. in that indication, and maybe how some of the other kind of competitor data in the recent history kind of maybe has shaped that viewpoint.

然後也許有點不被關注，cendakimab。我們似乎擴大了那裡的開發計劃，然後最近在日本增加了一項 III 期研究，例如嗜酸性粒細胞性胃腸炎。我想看看是否有更廣泛的計劃在美國針對這一跡像開展一項關鍵研究，以及近代歷史上其他一些競爭對手的數據可能如何塑造了這一觀點。

Sure. Thanks, Carter. This is Samit again. For deucravacitinib, UC as well as Crohn's Disease, both of those Phase II studies are ongoing. As we said earlier, that we do not have a proof of concept based on the first trial that we conducted with deucrava. But there are 2 studies that are ongoing, looking at a higher dose in UC in the ongoing study. And when those data are available, we'll certainly be able to analyze those and take that program forward once we have a proof of concept. So it is not off the charts, but more about looking to generate the data to make decisions as we look forward.

當然。謝謝，卡特。這又是薩米特。對於 deucravacitinib、UC 和克羅恩病，這兩項 II 期研究正在進行中。正如我們之前所說，我們沒有基於 deucrava 進行的第一次試驗進行概念驗證。但有 2 項研究正在進行中，在正在進行的研究中觀察 UC 中較高的劑量。當這些數據可用時，我們肯定能夠分析這些數據，並在獲得概念驗證後繼續推進該計劃。因此，這並不是不可能的，而是更多地希望生成數據來做出我們未來的決策。

For cendakimab, the U.S. study -- or the global study in eosinophilic esophagitis is already ongoing and enrolling patients as we speak. The Japan part is in addition to that, as you have already noted. So overall, the idea is to get the antibody to IL-13 into patients with eosinophilic esophagitis and look for additional indications. As you know, that we have a study ongoing in atopic dermatitis is a Phase II, and that proof of concept can then generate additional indications for further development.

對於 cendakimab，美國研究——或者說全球嗜酸性粒細胞性食管炎研究已經在進行中，並正在招募患者。正如您已經指出的，日本部分是除此之外的。總的來說，我們的想法是將 IL-13 抗體注入嗜酸性食管炎患者體內，並尋找其他適應症。如您所知，我們正在進行一項針對特應性皮炎的研究，該研究處於第二階段，概念驗證可以為進一步開發產生更多跡象。

Next, we'll go next to Matt Phipps with William Blair.

接下來，我們將與威廉·布萊爾一起前往馬特·菲普斯。

You all announced positive TRANSFORM results in June a couple of weeks before a similar announcement from YESCARTA. Yet, they have a PDUFA date in April and we're still kind of waiting on the PDUFA date for Breyanzi. Are there any risks to meeting the 2022 approval milestone there?

你們都在 6 月份宣布了積極的 TRANSFORM 結果，幾週後 YESCARTA 也發布了類似的公告。然而，他們的 PDUFA 日期是四月份，我們仍在等待 Breyanzi 的 PDUFA 日期。實現 2022 年批准里程碑是否存在任何風險？

And then, Samit, some 3 Phase IIIs of bempeg coming up this year. Do you think those have equal probability of success? Or is there one indication you think that's more likely based on where high dose IL-2 has been more effective?

Samit，今年將有 3 個 Bempeg III 期臨床試驗。您認為這些成功的可能性相同嗎？或者是否有一種跡象表明您認為這種情況更有可能是基於高劑量 IL-2 更有效的地方？

Thanks, Matt, for the questions. On Breyanzi, as you know, we don't necessarily declare our filings until we have heard from the FDA from the acceptance perspective. So as time goes, we will certainly be able to share more in terms of the filing and the PDUFA dates, et cetera. And we are certainly very, very pleased with the data that we have.

謝謝馬特提出的問題。關於 Breyanzi，如您所知，在收到 FDA 的受理意見之前，我們不一定會宣布我們的申請。因此，隨著時間的推移，我們肯定能夠在申請和 PDUFA 日期等方面分享更多信息。我們當然對我們擁有的數據非常非常滿意。

As well as that Breyanzi has a large development program. So additional trials are already ongoing in CLL, follicular lymphoma as well as for additional indications in indolent NHL. We're certainly looking forward to launching the second-line indication, as Chris mentioned earlier during the call, in that indication as well, in the second line of BCL.

Breyanzi 還有一個龐大的開發計劃。因此，針對 CLL、濾泡性淋巴瘤以及惰性 NHL 的其他適應症的額外試驗已經在進行中。正如 Chris 之前在電話會議中提到的那樣，我們當然期待在 BCL 的第二行中推出二線指示。

For bempeg, certainly, it is data dependent. We are working with Nektar as well to read out these studies in melanoma as well as in renal cell and bladder cancer. Just as a reminder, these indications were chosen based on those Phase II data that we had seen early on. But each study stands on its own, and the data will dictate how we proceed further in terms of future development.

對於 bempeg 來說，當然，它依賴於數據。我們還與 Nektar 合作，宣讀這些關於黑色素瘤以及腎細胞癌和膀胱癌的研究。提醒一下，這些適應症是根據我們早期看到的 II 期數據選擇的。但每項研究都是獨立的，數據將決定我們如何進一步推進未來的發展。

Next, we'll go to Matthew Harrison with Morgan Stanley.

接下來，我們將採訪摩根士丹利的馬修·哈里森。

This is Charlie Yang on for Matthew. First on Milvexian, can you say what amount of incremental bleeding in the stroke prevention study is acceptable clinically?

我是查理·楊（Charlie Yang）為馬修（Matthew）代言。首先關於Milvexian，您能說一下卒中預防研究中臨床可以接受的增量出血量是多少嗎？

And second, can you provide more details regarding the REMS and what that would look like? So for example, how frequent might patients need to be monitored.

其次，您能否提供有關 REMS 的更多詳細信息以及它會是什麼樣子？例如，患者需要多久接受一次監測。

And lastly, on Abecma, as you kind of walk through the earlier lines of therapy, can you talk about in terms of the prioritization of studies these versus commercial supply? And I guess what are the commercial opportunity relative to kind of current indication?

最後，關於 Abecma，當您回顧早期的治療方案時，您能談談這些研究與商業供應的優先順序嗎？我想相對於當前的跡像有哪些商業機會？

Okay. I'll start off. So first of all, for Milvexian in terms of what amount of bleed is acceptable, look, it is all dependent. And certainly, we don't want to see any increase in bleed compared to the control arm. So that's how you have to compare and contrast. And we certainly have historical data from other therapies as well as how patients are treated today. So we'll have to put that into context as we look at Milvexian program. But there are no numbers that I can share today with you as to how to start looking at or projecting out those numbers.

好的。我就開始吧。所以首先，對於 Milvexian 來說，多少出血量是可以接受的，看，這都是依賴的。當然，與控制臂相比，我們不希望看到出血增加。所以這就是你必須進行比較和對比的方式。我們當然有其他療法的歷史數據以及當今患者的治療方式。因此，當我們研究米爾維先計劃時，我們必須將其置於上下文中。但我今天無法與大家分享如何開始研究或預測這些數字。

From the REMS perspective for mavacamten, once again, we are not going to get into specifics. But as we have spoken before, what we are looking forward to is how patients are really managed in the clinic today.

從 mavacamten 的 REMS 角度來看，我們不會再討論細節。但正如我們之前所說，我們期待的是今天診所如何真正管理患者。

We have to go back to what Chris talked about earlier, the basic mechanism of the drug for mavacamten is myosin inhibition. And we want to ensure that the patients are treated in a safe way so that we don't cause the heart to "relax" too much and decrease the ejection fraction. And that's the intent and the way the patients are currently managed on a continuous or ongoing basis, is periodic echocardiographies. So more to follow on that as we get to the PDUFA date and final approval and full package of REMS and overall NDA approval.

我們要回到Chris之前談到的，mavacamten這個藥物的基本機制是肌球蛋白抑制。我們希望確保患者得到安全的治療，這樣我們就不會導致心臟過度“放鬆”並降低射血分數。這就是目前對患者進行連續或持續管理的目的和方式，即定期超聲心動圖檢查。當我們獲得 PDUFA 日期、最終批准以及完整的 REMS 和總體 NDA 批准時，還有更多後續內容。

From an Abecma perspective, certainly, the continuous progress in looking at the data from KarMMa and then KarMMa-3 and KarMMa-2 proof-of-concept this year will dictate the further evolution in terms of the overall development program. And studies are going to be as important as commercialization.

當然，從 Abecma 的角度來看，今年對 KarMMa 數據以及 KarMMa-3 和 KarMMa-2 概念驗證的持續進展將決定總體開發計劃的進一步發展。研究將與商業化一樣重要。

So certainly, from a supply perspective, Chris has spoken before. But certainly, I'll ask Chris to comment further on Abecma supplies for the clinic as well as commercial.

當然，從供應的角度來看，克里斯之前已經說過了。但當然，我會請 Chris 進一步評論 Abecma 的診所用品和商業用品。

Sure. And maybe I'll just make one comment on the REMS program, Charlie. The way that we have approached the REMS, obviously, we knew a REMS would likely -- would be likely with this asset. We've worked very closely from a commercial standpoint with Samit's team to ensure that the nature of that REMS fits very nicely into how physicians treat patients. And so we don't anticipate that there will be any particular challenges associated with that as we go into the launch.

當然。也許我只會對 REMS 計劃發表一點評論，查理。顯然，我們採用 REMS 的方式，我們知道 REMS 很可能會與該資產一起使用。我們從商業角度與 Samit 團隊密切合作，以確保 REMS 的性質非常適合醫生治療患者的方式。因此，我們預計在發佈時不會遇到任何與此相關的特殊挑戰。

And I think Samit's last point is particularly relevant as it relates to Abecma, which is that the way we've approached looking at clinical and commercial supply, is that, obviously, commercial supply is critically important. But it is equally important that we continue to prosecute our development program. And we're going to continue to make those trade-offs with both of those priorities in mind.

我認為 Samit 的最後一點特別重要，因為它與 Abecma 相關，即我們看待臨床和商業供應的方式，顯然商業供應至關重要。但同樣重要的是，我們繼續執行我們的發展計劃。我們將繼續在考慮到這兩個優先事項的情況下進行權衡。

Next, we'll go to Dane Leone with Raymond James.

接下來，我們將與雷蒙德·詹姆斯一起前往戴恩·萊昂內。

Two quick ones for me. Firstly, on mavacamten. We've seen biomarker data from MAVERICK that suggests the possibility of developing in nonobstructive and HFpEF. When do you think the team would be able to outline plan for plausibility of running a compelling clinical strategy in either of those indications?

對我來說兩個快點。首先，在mavacamten上。我們已經看到來自 MAVERICK 的生物標誌物數據表明存在非梗阻性和 HFpEF 的可能性。您認為團隊什麼時候能夠概述針對這些適應症運行令人信服的臨床策略的合理性計劃？

And then the second question would be, when do you think we might have some emerging data from the Dragonfly collaboration on IL-12 that the oncology community seems to be pretty excited about?

然後第二個問題是，您認為我們什麼時候可以從 Dragonfly 合作中獲得一些腫瘤學界似乎非常興奮的 IL-12 合作新數據？

Sure. I can take both of those, Dane. Thank you. For mavacamten, we are looking forward to initiating the first Phase III study in non-obstructive hypertrophic cardiomyopathy within 2022. And for HFpEF, the Phase II trial is now ongoing and looking forward to that proof-of-concept readout over time. And then that will dictate the future development in Phase III as well.

當然。我可以接受這兩個，丹恩。謝謝。對於 mavacamten，我們期待在 2022 年啟動第一個針對非梗阻性肥厚型心肌病的 III 期研究。對於 HFpEF，II 期試驗目前正在進行中，並期待隨著時間的推移獲得概念驗證結果。這也將決定第三階段的未來發展。

For Dragonfly, once again, it's an early phase development right now in Phase I, looking at single and then combination as well for our I-O platform. And as that data evolves, which we currently don't have in hand, and those will be presented at appropriate conferences as we look to the future.

對於 Dragonfly 來說，現在又處於第一階段的早期開發階段，我們的 I-O 平台正在考慮單一和組合。隨著這些數據的發展，我們目前手頭還沒有這些數據，當我們展望未來時，這些數據將在適當的會議上公佈。

Thanks, Samit. I think we can maybe go to our last question, please, Alan.

謝謝，薩米特。我想我們可以討論最後一個問題了，艾倫。

Our last question will be from Mohit Bansal with Wells Fargo Securities.

我們的最後一個問題將由富國銀行證券公司的 Mohit Bansal 提出。

This is [James] on for Mohit. Just a couple of quick questions. For deucrava, I know we're exploring new doses, but will you be rerunning the lab safety analysis to differentiate or rule out any JAK-like signals?

這是莫希特的[詹姆斯]。只是幾個簡單的問題。對於 deucrava，我知道我們正在探索新劑量，但您會重新運行實驗室安全分析以區分或排除任何類似 JAK 的信號嗎？

And then for the S1Ps, how is BMI -- or BMY expecting the S1P to be positioned relative to JAKs?

那麼對於 S1P，BMI（或 BMY）預計 S1P 相對於 JAK 的定位如何？

And any thoughts on competitiveness of Zeposia relative to etrasimod?

對於 Zeposia 相對於 etrasimod 的競爭力有什麼想法嗎？

So let me start with deucravacitinib. So we've already got 2 Phase III studies that have read out. And those safety data are all the way with a follow-up of 52 weeks, we've already shared. And we'll to continue to evolve as we look forward. We've also looked at the data and will be part of the submissions in China and Japan for studies that have been conducted in China and Japan with longer term, 1 year follow-up.

讓我從 deucravitinib 開始。我們已經讀出了 2 項 III 期研究。我們已經分享了這些安全數據，以及 52 週的隨訪數據。我們將繼續向前發展。我們還研究了這些數據，並將成為在中國和日本提交的研究的一部分，這些研究已在中國和日本進行，並進行了為期一年的長期隨訪。

So those are all in line with the safety profile that we have added. So we certainly do not look forward to doing additional analyses on the same data because we've conducted those. Long-term follow-ups will continue and see additional evolution. And certainly, those similar sorts of exercises of continuing to generate data at higher doses for other indications that we are studying will be evaluated when data are available.

所以這些都符合我們添加的安全配置文件。因此，我們當然不希望對相同的數據進行額外的分析，因為我們已經進行了這些分析。長期的後續行動將繼續進行，並看到更多的進展。當然，當數據可用時，我們將評估那些繼續以更高劑量為我們正在研究的其他適應症生成數據的類似練習。

From an S1P perspective, Chris, do you want...

從 S1P 的角度來看，Chris，你想要……

Sure, I'll take that one. So James, as I said earlier, we do expect that there's going to continue to be an evolution of JAK labeling that could continue to push those assets into later lines of therapy, if you will. From our perspective, we continue to be very happy with the profile from Zeposia, both from an efficacy, given the strong clinical remissions, as well as the clean safety profile.

當然，我會接受那個。因此，詹姆斯，正如我之前所說，我們確實預計 JAK 標籤將繼續發展，如果您願意的話，可以繼續將這些資產推向後續的治療領域。從我們的角度來看，我們仍然對 Zeposia 的概況感到非常滿意，無論是從療效、臨床緩解效果還是良好的安全性來看。

Our focus Continues to be drive awareness and overall volume. There may be opportunities longer term given the evolving JAK situation. But we're going to continue to be disciplined in how we approach this launch and executing against what we need to do in order to build volume.

我們的重點仍然是提高知名度和整體銷量。鑑於 JAK 形勢的不斷變化，從長遠來看可能存在機會。但我們將繼續嚴格遵守本次發布的方式，並根據我們需要做的事情來執行以增加銷量。

And with respect to differentiation against other future S1Ps in that space, again, I would just say that we're very confident in the profile that we have, and it's important that we execute effectively with the launch in UC. And that's where our commercial focus is.

關於與該領域其他未來 S1P 的差異化，我只想說，我們對我們擁有的形象非常有信心，並且重要的是我們在 UC 中有效地執行發布。這就是我們的商業重點所在。

Thank you. Thank you, Chris. Thanks, everyone, and I appreciate you participating in the call.

謝謝。謝謝你，克里斯。謝謝大家，我很感謝你們參與這次電話會議。

Let me just close by saying we're really pleased with our performance in the quarter. And much more broadly, our performance in 2021 positions us really well to deliver growth this year, in 2022, and beyond.

最後我要說的是，我們對本季度的表現非常滿意。更廣泛地說，我們 2021 年的業績使我們能夠在今年、2022 年及以後實現增長。

We have built a solid foundation, and I'm confident that, as our portfolio renewal gains traction this year, our company is well positioned to reach new heights, both for patients and shareholders. And I want to thank our employees for supporting very strong growth.

我們已經建立了堅實的基礎，我相信，隨著今年我們的投資組合更新獲得牽引力，我們公司已做好充分準備，為患者和股東達到新的高度。我要感謝我們的員工支持強勁的增長。

Thanks for being with us for the call. Our team remains available to ask -- to answer any additional questions you may have. And I wish all of you a good day. Thank you.

感謝您接受我們的來電。我們的團隊隨時可以詢問 - 回答您可能有的任何其他問題。祝大家有美好的一天。謝謝。

That does conclude today's conference. We thank everyone again for their participation.

今天的會議到此結束。我們再次感謝大家的參與。