施貴寶 (BMY) 2022 Q4 法說會逐字稿

Good morning. My name is Dennis, and I will be your conference operator today. At this time, I would like to welcome everyone to the Bristol-Myers Squibb Fourth Quarter 2022 Earnings Conference Call. (Operator Instructions)

早安.我叫丹尼斯，今天我將擔任您的會議主持人。現在，我歡迎大家參加百時美施貴寶 2022 年第四季財報電話會議。 （操作員指令）

I would now like to turn the conference over to Tim Power, Vice President of Investor Relations. Please go ahead.

現在，我想將會議交給投資者關係副總裁 Tim Power。請繼續。

Thank you, and good morning, everyone. Thanks for joining us this morning for our fourth quarter 2022 earnings call.

謝謝大家，早安。感謝您今天上午參加我們的 2022 年第四季財報電話會議。

Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. 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發言的還有我們的董事會主席兼首席執行官喬瓦尼·卡福里奧 (Giovanni Caforio)；以及我們的財務長David Elkins。參加今天電話會議的還有我們的首席商業化長 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've posted slides to bms.com that you can follow along with for Giovanni and David's remarks.

正如您所注意到的，我們已將幻燈片發佈到 bms.com，您可以關注 Giovanni 和 David 的演講。

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

在我們開始之前，我將宣讀我們的前瞻性聲明。在本次電話會議中，我們將對公司未來計畫和前景做出一些構成前瞻性陳述的陳述。由於各種重要因素（包括公司向美國證券交易委員會提交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有重大差異。這些前瞻性陳述代表我們截至今天的估計，不應被視為代表我們對任何未來日期的估計。我們明確表示不承擔更新前瞻性聲明的任何義務，即使我們的估計發生變化。

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 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。某些非 GAAP 財務指標與最具可比性的 GAAP 指標的對帳表可在 bms.com 上查閱。

With that, I'll hand it over to Giovanni.

說完這些，我就把它交給喬瓦尼。

Thank you, Tim, and good morning, everyone. Starting on Slide 4. I am pleased to report another strong quarter for Bristol-Myers Squibb, concluding a very successful year.

謝謝你，提姆，大家早安。從第 4 張幻燈片開始。

Last year was an important year for our company, the first with Revlimid generics. Given that, I am very proud to say that in 2022, we grew our business and made tremendous progress advancing our pipeline, including launching 3 new first-in-class medicines and progressing 6 promising programs into registrational development.

去年對我們公司來說是重要的一年，這是我們公司推出 Revlimid 仿製藥的第一年。有鑑於此，我很自豪地說，2022 年，我們的業務成長了，並在推進我們的產品線方面取得了巨大進展，包括推出 3 種新的一流藥物，並將 6 個有前景的項目推進到註冊開發階段。

While David will provide additional details on the financials in a moment, I will point out a few highlights. Last year, we delivered revenue growth of 3%, adjusting for foreign exchange. Importantly, growth was driven by our in-line and new product portfolios. So I am pleased to note that we delivered continued strong growth in the fourth quarter for these assets, up 12% adjusting for foreign exchange.

大衛稍後會提供有關財務狀況的更多細節，但我將指出一些亮點。去年，經外匯調整後，我們的收入成長了 3%。重要的是，成長是由我們的線上和新產品組合所推動的。因此，我很高興地註意到，我們在第四季度這些資產繼續實現了強勁增長，經外匯調整後增長了 12%。

We also grew our earnings, including non-GAAP EPS growth of 8% for the full year. As we start 2023, I am confident we have established a strong foundation for Bristol-Myers Squibb. As you will note from our guidance, we expect to grow both revenue and non-GAAP EPS this year. Importantly, we remain on track to achieve the commitments we have made for 2025. Given increasing confidence in our new product portfolio and continued progress with our broader pipeline, we see multiple paths to growth through 2030.

我們的收益也實現了成長，其中全年非公認會計準則每股收益成長 8%。隨著 2023 年的到來，我相信我們已經為百時美施貴寶奠定了堅實的基礎。正如您從我們的指引中註意到的那樣，我們預計今年的營收和非 GAAP 每股盈餘都將成長。重要的是，我們仍在按計劃實現我們對 2025 年做出的承諾。

Let me now provide some perspective on 2022. On Slide 5, you can see our overall pipeline execution last year. I am very pleased with our progress, which further supports renewal of our portfolio. While we advanced on many fronts, I would like to highlight a few accomplishments.

現在，讓我提供一些關於 2022 年的觀點。我對我們的進展感到非常高興，這進一步支持了我們投資組合的更新。儘管我們在許多方面都取得了進步，但我還是想強調一些成就。

Approval of 3 first-in-class medicines, including Opdualag, Camzyos and Sotyktu, which address areas of high unmet medical need and have significant commercial potential.

核准3種同類首創藥物，包括Opdualag、Camzyos和Sotyktu，這些藥物針對的是尚未滿足的醫療需求領域，具有巨大的商業潛力。

Further progress expanding the reach of our new product portfolio, including an important expansion opportunity for Reblozyl in first-line MDS with COMMANDS, positive top line growth of KarMMa-3 based on which Abecma is the first BCMA CAR-T to have demonstrated superiority to standard regimens in relapsed and refractory multiple myeloma. And initiation of registrational trials for Sotyktu in lupus.

我們新產品組合覆蓋範圍的進一步擴大，包括 Reblozyl 在與 COMMANDS 合作的一線 MDS 中的重要擴展機會，以及 KarMMa-3 的積極營收增長（基於此，Abecma 是第一個在復發和難治性多發性骨髓瘤中證明優於標準方案的 BCMA CAR-T）。並啟動Sotyktu治療狼瘡的註冊試驗。

Remember, in the Phase II study, Sotyktu demonstrated an encouraging profile in this harder-to-treat disease. We believe lupus can be an important expansion opportunity for the brand.

請記住，在第二階段的研究中，Sotyktu 在治療這種難以治療的疾病方面表現出了令人鼓舞的效果。我們相信狼瘡可以成為品牌的重要擴張機會。

Progress with the next generation of medicines includes important proof-of-concept data for Milvexian in secondary stroke prevention, enabling the initiation of the Phase III program this year and a positive trial for our LPA1 asset in lung fibrosis.

下一代藥物的進展包括 Milvexian 在二級中風預防方面的重要概念驗證數據，這使得我們今年能夠啟動 III 期計劃，並對我們的 LPA1 資產在肺纖維化方面進行了積極的試驗。

This asset has come into focus only recently and is a prime example of the optionality that comes from having a broad pipeline. We are looking forward to presenting data and starting Phase III trials for this asset later this year.

這項資產最近才開始受到關注，是擁有廣泛管道所帶來的可選性的典型例子。我們期待在今年稍後展示數據並開始該資產的第三階段試驗。

On Slide 6, you can see how we strengthened the outlook for our new product portfolio, which, as you know, is central to our strategy of renewing our portfolio over the coming years.

在第 6 張投影片上，您可以看到我們如何加強新產品組合的前景，正如您所知，這對於我們未來幾年更新產品組合的策略至關重要。

Our pipeline execution and strong commercial momentum position us well to achieve $10 billion to $13 billion of risk-adjusted revenue in 2025. And as a result of the strong progress with our pipeline, we have significantly derisked the $25 billion plus of long-term non-risk-adjusted revenue potential. As you can also see on this slide, we continue to see exciting catalysts ahead for these assets.

我們的產品線執行力和強勁的商業勢頭使我們預計在 2025 年實現 100 億至 130 億美元的風險調整後收入。正如您在這張投影片上看到的，我們繼續看到這些資產未來令人興奮的催化劑。

So turning to our scorecard for this year on Slide 7. It's encouraging to observe the breadth of catalysts we see ahead as a company in the near term. I'll point out a few highlights.

現在讓我們來看看幻燈片 7 上的今年的記分卡。我將指出幾個亮點。

Just last week, we announced our Phase I/II trial for Breyanzi in relapsed refractory CLL met the primary endpoint. In Europe, we expect to launch Camzyos in obstructive HCM and are pleased to have received positive CHMP opinion for our first and only selective TYK2 inhibitor, Sotyktu. Our ROS1 inhibitor, repotrectinib is expected to be filed in the U.S. in lung cancer.

就在上週，我們宣布 Breyanzi 治療復發難治性 CLL 的 I/II 期試驗達到了主要終點。在歐洲，我們有望推出用於治療阻塞性 HCM 的 Camzyos，並且很高興我們的首個也是唯一一個選擇性 TYK2 抑制劑 Sotyktu 獲得了 CHMP 的正面評價。我們的 ROS1 抑制劑 repotrectinib 預計將在美國提交肺癌治療申請。

We have an important expansion opportunity for Reblozyl in first-line MDS. Along with our partners at Janssen, we have embarked on registrational trials for milvexian, and we expect to move Abecma into earlier lines of therapy.

我們為 Reblozyl 在 MDS 第一線治療領域帶來了重要的擴張機會。我們與楊森的合作夥伴一起，已著手對 milvexian 進行註冊試驗，並希望將 Abecma 推向更早的治療領域。

Finally, we are further advancing our multiple myeloma CELMoD program with a head-to-head study of iberdomide versus Revlimid in the post-transplant maintenance setting. As we have done in the prior years, we look forward to updating you on our progress as we continue to advance our pipeline and further support our portfolio renewal.

最後，我們正在進一步推進多發性骨髓瘤 CELMoD 項目，在移植後維持治療中對伊貝多胺與來那度胺進行頭對頭研究。正如我們前幾年所做的那樣，我們期待向您通報我們的進展，因為我們將繼續推進我們的產品線並進一步支持我們的產品組合更新。

Turning to Slide 8. I'd like to remind you about what we've accomplished in the past few years and how that prepares us well for the near, mid and long term. When we began the transformation of our company 3 years ago, we told you what we believed we could achieve and we have delivered across the board.

翻到第 8 張投影片。三年前，當我們開始公司轉型時，我們就告訴大家我們相信我們能夠實現什麼，而且我們已經全面實現了這個目標。

Financially, we have grown our company, over delivered synergies, reduced our debt and generated significant cash flows. We have launched all 9 new medicines, including 3 first-in-class products that were approved last year. And we've continued to execute disciplined business development to further support our growth profile in the future. Our record of execution further strengthens my confidence in our ability to renew our portfolio and deliver long-term growth.

在財務方面，我們的公司發展壯大、實現了超額的協同效應、減少了債務並產生了大量現金流。我們已經上市了全部9種新藥，其中包括去年核准的3種同類首創產品。我們將繼續執行嚴格的業務發展，以進一步支持我們未來的成長前景。我們的執行記錄進一步增強了我對我們更新投資組合和實現長期成長的能力的信心。

With all of this in mind, let me move to Slide 9 to discuss our outlook for this year and beyond. As you know, we expect to drive growth through 2025 and sustained strong profitability as we transform our portfolio. And that journey continues this year. We delivered growth through Revlimid generics in 2022. And as you can see from our guidance today, we expect to continue to grow this year.

考慮到所有這些，請允許我轉到幻燈片 9 來討論我們對今年及以後的展望。如您所知，我們預計到 2025 年，隨著投資組合的轉變，我們將實現成長並保持強勁的獲利能力。這趟旅程今年也將繼續。我們在 2022 年透過 Revlimid 仿製藥實現了成長。

With the focus turning to the second half of the decade, we continue to see multiple paths to growth, driven by growth of the new products, contribution from our advancing late-stage pipeline, including Milvexian LPA1 and the CELMoDs, and significant optionality from our early pipeline, complemented by flexibility for additional business development. All the while, we are transforming our portfolio to be younger, more diversified and more resilient in the face of an increasingly complex pricing environment in the U.S. and internationally.

隨著焦點轉向下個十年，我們繼續看到多種成長途徑，這些成長途徑由新產品的成長、我們不斷推進的後期產品線（包括 Milvexian LPA1 和 CELMoD）的貢獻、以及我們早期產品線的顯著可選性所推動，並輔以額外業務開發的靈活性。面對美國和國際上日益複雜的定價環境，我們一直以來都在轉變我們的投資組合，使其更加年輕、更加多元、更具彈性。

Before I turn to David, let me express my gratitude to our teams across the globe, starting with our research and development organization, which had a stellar 2022.

在向 David 致謝之前，請允許我向我們遍布全球的團隊表示感謝，首先是我們的研發部門，他們在 2022 年取得了輝煌的成績。

As you will have seen, this week, we announced Dr. Rupert Vessey's decision to retire, effective July 3. I want to thank Rupert for his extraordinary contributions since he joined BMS as a result of the acquisition of Celgene. Rupert led the successful integration of research and the development of a strong pipeline across all stages of development.

正如您所看到的，本週，我們宣布了 Rupert Vessey 博士決定退休，該決定將於 7 月 3 日生效。魯珀特領導了成功整合研究和開發各個開發階段的強大管道的行動。

We are now combining development across early and late stage under Samit's leadership and preparing to transition the research organization to report to Dr. Robert Plenge, who will serve as EVP and Chief Research Officer, when Rupert retires this summer.

目前，我們正在 Samit 的領導下結合早期和後期開發，並準備將研究機構轉交給 Robert Plenge 博士匯報，當 Rupert 今年夏天退休時，Robert Plenge 博士將擔任執行副總裁兼首席研究官。

The focus and the termination of these leaders and all of our teams will enable us to continue to deliver for the patients depending on us.

這些領導和我們所有團隊的關注和終止將使我們能夠繼續為依賴我們的患者提供服務。

I'll now turn it over to David to walk you through the financials. David?

現在我將把話題交給大衛，讓他向大家介紹財務狀況。戴維？

Thank you, Giovanni, and thank you all again for joining our call today. I know this is a busy morning for all of you. .

謝謝你，喬瓦尼，再次感謝大家今天參加我們的電話會議。我知道對你們所有人來說今天早上都是忙碌的。 。

As Giovanni mentioned, 2022 was another solid year of execution for Bristol-Myers Squibb. Let's get started with our top line performance on Slide 11. Unless otherwise stated, all comparisons are made versus the same period in 2021 and sales performance growth rates will be discussed on an underlying basis, which excludes the impact of foreign exchange.

正如喬瓦尼所提到的，2022 年對百時美施貴寶來說又是執行力紮實的一年。讓我們從投影片 11 的營收表現開始。

We delivered on our full year commitments with sales of approximately $46 billion with growth of 3%. Demand for our diversified in-line and new product portfolio was strong, with revenue growth of 13% for the year, more than offsetting the loss of exclusivity for Revlimid in the first year of generic entry.

我們兌現了全年承諾，銷售額約 460 億美元，成長 3%。我們多樣化的在研產品和新產品組合的需求強勁，全年收入增長了 13%，超過了仿製藥進入第一年 Revlimid 獨佔權的損失。

Let me dive deeper now into fourth quarter and full year performance of our new product portfolio on Slide 12. Global revenues in the quarter were $645 million, up 87%. While full year revenues topped over $2 billion, nearly doubling over 2021. With 9 new product approvals and multiple additional indications coming to fruition, we have an increasingly derisked new product portfolio. This provides us confidence that we are on track to deliver the potential of our new product portfolio with $25 billion of non-risk-adjusted revenue expected at the end of the decade.

現在，讓我在第 12 張投影片上更深入地介紹我們新產品組合在第四季和全年的業績。而全年收入突破 20 億美元，幾乎比 2021 年翻了一番。這使我們有信心，我們有望充分發揮我們新產品組合的潛力，並預計到2020年將實現250億美元的非風險調整後收入。

Moving to Slide 13 to discuss our performance of our solid tumor portfolio. Global Opdivo sales reflect strong demand for our newly launched and core indication with double-digit growth in the fourth quarter and the full year. In the U.S., fourth quarter revenue saw full year sales growth strong, growing 13% and 15%, respectively. This growth was primarily driven by demand for our new metastatic and adjuvant indications partially offset by declining second-line eligibility as well as some use of Opdualag in first-line melanoma.

轉到投影片 13，討論我們的實體腫瘤產品組合的表現。 Opdivo 的全球銷售反映了對我們新推出的核心適應症的強勁需求，第四季和全年都實現了兩位數的成長。在美國，第四季營收和全年銷售成長強勁，分別成長13％和15％。這一增長主要得益於對我們新的轉移性和輔助適應症的需求，但二線治療合格率的下降以及 Opdualag 在一線黑色素瘤治療中的部分使用部分抵消了這一增長。

Internationally, revenues grew 20% in the fourth quarter and 14% for the full year. Fourth quarter revenue growth was largely driven equally by demand and timing of shipments. Demand was primarily driven to new indications, particularly first-line lung in upper GI cancers. As we look to this year, we expect growth of Opdivo to continue. This growth will come from an expanded indications in both early and late-stage cancers.

國際方面，第四季營收成長了 20%，全年營收成長了 14%。第四季的營收成長主要受到需求和出貨時間的推動。需求主要源自於新適應症，特別是上消化道癌症的第一線肺癌治療。展望今年，我們預計 Opdivo 將持續成長。這種增長將源於早期和晚期癌症適應症的擴大。

Now turning to our first-in-class LAG-3 inhibitor, Opdualag, which had an impressive first year on the market, approved in the U.S. in late March, Opdualag generated sales of $252 million in 2022. Sales in the fourth quarter had strong sequential growth of 24% versus quarter 3. With first-line melanoma market share now in the high teens, we continue to see room for growth of Opdualag in first-line melanoma, where PD-1 monotherapy share still is approximately 20%. And further potential with pivotal studies in adjuvant melanoma and second-line plus colorectal cancer underway.

現在來看看我們的首創 LAG-3 抑制劑 Opdualag，該藥物上市第一年就取得了令人印象深刻的成績，並於 3 月底在美國獲得批准，Opdualag 在 2022 年的銷售額達到 2.52 億美元。的份額仍約為 20%。並且正在進行的輔助黑色素瘤和二線及大腸癌的關鍵研究具有進一步的潛力。

On Slide 14, let's discuss our growing cardiovascular portfolio, starting with Eliquis, which had another great year. Global revenues in the fourth quarter and the full year grew 6% and 14%, respectively. In the U.S., fourth quarter sales increased 15%, driven primarily by demand and favorable gross to net adjustments.

在幻燈片 14 上，讓我們討論一下我們不斷增長的心血管產品組合，首先是 Eliquis，它又度過了一個輝煌的一年。第四季和全年全球營收分別成長6%和14%。在美國，第四季銷售額成長了 15%，主要原因是需求和有利的毛利與淨利調整。

Internationally, Eliquis is the leading OAC in many countries. Given high market shares across these countries, demand growth has been offset by pricing measures as well as generic entry in Canada, the U.K. and the Netherlands.

在國際上，Eliquis 是許多國家領先的 OAC。鑑於這些國家較高的市場份額，需求成長被定價措施以及加拿大、英國和荷蘭的仿製藥進入所抵消。

Now turning to our first-in-class myosin inhibitor, Camzyos. Sales in the fourth quarter were $16 million. We are pleased with the progress we have made since the launch in May of 2022. We laid a strong foundation of REMS certified over 2,600 health care professionals and enabled key centers to get operationally ready to make Camzyos available to patients. We also significantly increased the number of patients on commercial dispensed drug, which provides strong momentum heading into this year. We look forward to continuing this momentum as well as bringing Camzyos to European patients with approval expected by midyear.

現在來談談我們一流的肌球蛋白抑制劑 Camzyos。第四季的銷售額為1600萬美元。我們對自 2022 年 5 月推出以來所取得的進展感到滿意。我們也大幅增加了使用商業配藥的患者數量，這為今年的發展提供了強勁動力。我們期待繼續保持這一勢頭，並將 Camzyos 帶給歐洲患者，預計今年年中將獲得批准。

Moving to our hematology portfolio on Slide 15, starting with Revlimid. Global sales for the full year were approximately $10 billion, impacted by generic entry. As we noted last year, we expected variability quarter-to-quarter. And in 2022, we saw slower-than-anticipated utilization of generic lenalidomide in the U.S.

轉到幻燈片 15 上的血液學產品組合，首先是 Revlimid。受仿製藥進入的影響，全年全球銷售額約 100 億美元。正如我們去年指出的那樣，我們預計每個季度都會有所變化。 2022 年，我們發現美國仿製藥來那度胺的使用速度低於預期。

With favorability in 2022, an anticipated increase in generic volume this year, we expect Revlimid revenues to be approximately $6.5 billion in 2023. We continue to expect an average $2.5 billion annual step down as a reasonable assumption for 2024 and 2025.

由於 2022 年前景看好，預計今年仿製藥銷量將增加，我們預計 2023 年 Revlimid 的營收將達到約 65 億美元。

Pomalyst global revenues continue to grow in the fourth quarter and for the full year, driven primarily by demand for triple-based regimens in earlier lines of therapy and extending duration of treatment for patients. As usual, in the first quarter, I would like to remind you of the typical seasonality of Revlimid and Pomalyst experience due to patients entering the Medicare coverage scrap early in the year.

Pomalyst 第四季及全年全球營收持續成長，主要受早期療法對三重方案的需求以及延長病患治療時間的推動。像往常一樣，在第一季度，我想提醒您，Revlimid 和 Pomalyst 的典型季節性是由於患者在年初進入醫療保險覆蓋範圍。

Now moving to Reblozyl, our first-in-class EMA. Demand for Reblozyl was strong with fourth quarter and full year sales growing over 30%. In the U.S., revenues grew over 20% in both the fourth quarter and full year. We have made great progress since launch by increasing patient adherence, extending treatment durations and accelerating switches when ESAs fail.

現在轉向 Reblozyl，我們的首創 EMA。 Reblozyl 的需求強勁，第四季和全年銷售額成長超過 30%。在美國，第四季和全年營收均成長超過20％。自推出以來，我們透過提高患者的依從性、延長治療時間和加速 ESA 失效時的轉換取得了巨大進展。

Internationally, Reblozyl continues to launch in different markets across the globe with launches now in 16 markets outside the U.S. Growth continues to be driven by demand in both MDS and beta thalassemia-associated anemia and attaining reimbursement in additional countries.

在國際上，Reblozyl 繼續在全球不同市場推出，目前已在美國以外的 16 個市場推出。

Turning to our differentiated cell therapy portfolio, Abecma and Breyanzi, our first-in-class BCMA cell therapy, Abecma, continued its robust performance. Global revenues for the full year were $388 million versus $164 million in 2021. This represents strong growth year-over-year reflecting significant patient demand and the work the company has done to increase manufacturing capacity. We remain focused on continuing to ramp up capacity and believe this will enable us to get Abecma to more patients with highly refractory myeloma as well as preparing to move into earlier lines of therapy.

談到我們差異化的細胞療法產品組合 Abecma 和 Breyanzi，我們一流的 BCMA 細胞療法 Abecma 繼續保持強勁的表現。全年全球收入為 3.88 億美元，而 2021 年為 1.64 億美元。我們將繼續專注於繼續提高產能，並相信這將使我們能夠將 Abecma 帶給更多高度難治性骨髓瘤患者，並為進入早期治療做好準備。

Lastly, moving to our best-in-class CD19 cell therapy, Breyanzi. Global sales for the year were $182 million, more than doubling over 2021. Sales in the quarter reflect strong demand and hard work of our teams to expand supply. Looking to this year, we continue to expect growth driven by demand for Breyanzi and second-line plus large B-cell lymphoma, and we remain focused on continuing to build manufacturing capacity to further support the uptake and prepare for additional indications.

最後，我們來談談我們一流的 CD19 細胞療法 Breyanzi。本年度全球銷售額為 1.82 億美元，比 2021 年增長了一倍多。展望今年，我們將繼續預期 Breyanzi 和二線以上大型 B 細胞淋巴瘤的需求將推動成長，我們仍將專注於繼續建立製造能力，以進一步支持吸收並為更多適應症做好準備。

Now let's move to our expanded immunology portfolio on Slide 16, starting with our first-in-class S1P agonist, Zeposia. Fourth quarter sales grew 69%, while full year global sales nearly doubled, driven by increased demand in multiple sclerosis and ulcerative colitis. Our strategy to expand volume and to improve commercial access is materializing.

現在讓我們轉到幻燈片 16 上的擴展免疫學產品組合，從我們的同類首創 S1P 激動劑 Zeposia 開始。第四季銷售額成長 69%，而受多發性硬化症和潰瘍性結腸炎需求增加的推動，全年全球銷售額幾乎翻了一番。我們擴大產量和改善商業通路的策略正在實現。

We've made progress with several plans with either 0 or 1 step edit, which will meaningfully expand access as we move in 2023. We expect continued growth of Zeposia to evolve primarily from MS today to UC over time. And remember, as with any new immunology medicine heading into the first quarter, the typical dynamics of co-pays resetting each year tend to impact the first quarter performance as additional co-pay supports -- affects gross to net adjustments. Internationally, we are continuing to focus on securing reimbursement in additional markets to get Zeposia to more patients living with MS and UC.

我們在幾個計劃中取得了進展，這些計劃包括 0 步或 1 步編輯，這將在 2023 年顯著擴大訪問權限。請記住，與進入第一季的任何新型免疫藥物一樣，每年重新設定的共同支付的典型動態往往會影響第一季的業績，因為額外的共同支付支持會影響總的淨調整。在國際上，我們將繼續致力於確保在其他市場的報銷，以便讓更多患有 MS 和 UC 的患者能夠使用 Zeposia。

Finally, turning to our first-in-class TYK2 inhibitor for moderate to severe plaque psoriasis, Sotyktu. We're extremely pleased with the U.S. launch so far. Still early days, but physician feedback has been outstanding. As of December, we had over 2,000 script equivalents on BRIDGE and commercial drug.

最後，讓我們來談談我們針對中度至重度斑塊狀乾癬的首創 TYK2 抑制劑 Sotyktu。到目前為止，我們對美國市場的發布感到非常滿意。雖然還處於早期階段，但醫生的回饋非常出色。截至 12 月，我們在 BRIDGE 和商業藥品上擁有超過 2,000 個劇本等價物。

Since then, we continue to make progress in new scripts and see that the use of Sotyktu is roughly evenly split across systematic naive patients, Otezla switch patients and biologic switch patients. We remain focused on driving demand for this new medicine as the oral choice and ensuring as many patients as possible get Sotyktu to enable broader formulary positions in 2024. Internationally, we are now approved in Japan and Canada with expected European approval by midyear.

從那時起，我們繼續在新的處方方面取得進展，並發現 Sotyktu 的使用在系統性初治患者、Otezla 轉換患者和生物製劑轉換患者中大致平均分配。我們將繼續專注於推動這種口服新藥的需求，並確保盡可能多的患者獲得 Sotyktu，以在 2024 年擴大處方範圍。

Switching gears to our fourth quarter P&L on Slide 17. Having just covered sales performance, let me walk you through a few non-GAAP key line items. As expected, fourth quarter gross margin was impacted primarily by product mix and higher manufacturing costs. For the full year, gross margin was in line with our prior guidance at approximately 79%. Excluding acquired in-process R&D, fourth quarter and full year operating expenses decreased primarily due to reallocation of investments behind our growth opportunities and the impact from foreign exchange and dilution from the Turning Point acquisition.

現在轉到投影片 17 上的第四季損益表。如預期，第四季的毛利率主要受到產品組合和製造成本上升的影響。全年毛利率與我們先前預期的一致，約為 79%。除收購的在研發外，第四季度和全年營業費用下降的主要原因是我們對成長機會的投資重新分配以及外匯影響和 Turning Point 收購的稀釋。

Acquired in-process R&D in the quarter was $52 million, which was partially offset by $16 million of licensing income that benefited OI&E in the quarter. Fourth quarter effective tax rate was approximately 11%, driven by earnings mix and one-time items with the full year tax rate of approximately 15%.

本季收購的在研研發費用為 5,200 萬美元，部分被本季使 OI&E 受益的 1,600 萬美元授權收入所抵銷。第四季有效稅率約為 11%，受獲利組合和一次性項目的影響，全年稅率約為 15%。

Overall, fourth quarter earnings per share was $1.82. From a full year perspective, we ended the year at the upper end of our guidance range at $7.70, representing 8% over previous year.

總體而言，第四季每股收益為 1.82 美元。從全年角度來看，我們以 7.70 美元的預期上限結束了這一年度，比去年同期增長了 8%。

Moving to the balance sheet and capital allocation on Slide 18. Cash flow from operations in the fourth quarter was $3.3 billion. The company's balance sheet remained strong with approximately $9 billion of cash and marketable securities on hand as of December 31.

轉到投影片 18 上的資產負債表和資本配置。該公司的資產負債表依然強勁，截至 12 月 31 日，手頭上有約 90 億美元的現金和有價證券。

Our capital allocation priorities are unchanged. Business development remains a top priority to further renew and diversify our portfolio and strengthen our growth outlook while also focused on balance sheet strength and returning capital to shareholders.

我們的資本配置重點並沒有改變。業務發展仍然是我們的重中之重，旨在進一步更新和多樣化我們的投資組合、加強我們的成長前景，同時也注重資產負債表實力和向股東返還資本。

We have executed several early stage business development deals as well as acquiring Turning Point Therapeutics last year. Our strong balance sheet allows us to be size-agnostic on deals. As it relates to balance sheet strength in 2022, we reduced debt by over $5 billion, and we are committed to maintaining a strong investment-grade credit rating.

我們已經執行了幾項早期業務發展交易，並在去年收購了 Turning Point Therapeutics。我們強大的資產負債表使得我們在交易中不受規模限制。就 2022 年的資產負債表實力而言，我們減少了 50 多億美元的債務，並致力於保持強勁的投資等級信用評級。

And finally, as it relates to returning capital to shareholders, we have a long-standing track record of paying dividend for 91 consecutive years and recently grew the dividend for the 14th consecutive year. We remain committed to growing the dividend, subject to Board approval and continue to be opportunistic on share repurchases, with approximately $7 billion remaining in our share repurchase authorization.

最後，就向股東返還資本而言，我們擁有連續 91 年派發股息的長期記錄，並且最近連續第 14 年增加股息。我們仍致力於增加股息，但須經董事會批准，並繼續掌握股票回購機會，目前我們的股票回購授權餘額約為 70 億美元。

Let me close with our 2023 non-GAAP guidance on Slide 19. Due to unpredictable macroeconomic factors and large swings in foreign exchange last year, we are providing guidance on a reported basis as well as an underlying basis, which assumes currency remains consistent with prior year.

最後，讓我以幻燈片 19 上的 2023 年非 GAAP 指引作為結束。

We expect 2023 revenues to grow approximately 2% on a reported and constant currency basis. This reflects our confidence that our in-line and new product portfolios will more than offset the LOE impact from Revlimid and Abraxane. We expect Revlimid sales to be approximately $6.5 billion, which assumes additional step-up to generic manufacturers later in Q1 as well as continued variability quarter-to-quarter.

我們預計 2023 年營收將以報告和固定匯率計算成長約 2%。這反映了我們的信心，即我們的線上和新產品組合將足以抵消 Revlimid 和 Abraxane 帶來的 LOE 影響。我們預計 Revlimid 的銷售額約為 65 億美元，假設第一季後期仿製藥製造商的銷售額進一步增加，並且各個季度的銷售額繼續保持波動。

With the momentum of our new product portfolio, we expect it to roughly double versus last year and will be approximately $4 billion. As it relates to our line item guidance for the year, we expect our gross margin to be approximately 77%, which reflects a shift in product mix. We do not predict acquired in-process R&D.

隨著我們新產品組合的不斷發展，我們預計其銷售額將比去年翻一番，達到約 40 億美元。與我們今年的專案指導相關，我們預計毛利率約為 77%，這反映了產品結構的變化。我們不預測獲得正在進行的研發。

So excluding this, we expect our total operating expenses to decline in the low single-digit range. This reflects a reallocation of cost and efficiency initiatives in MS&A as we continue to invest in our new launches.

因此，除去這項費用，我們預計總營運費用將下降至個位數的低點。這反映了我們隨著繼續投資新產品而對 MS&A 的成本和效率舉措的重新分配。

R&D expenses are expected to be largely in line with last year due to our dynamic portfolio of studies reading out and new study starts. We project our tax rate to be approximately 17%, reflecting changes to Puerto Rico tax laws and product mix.

由於我們不斷更新的研究成果和新研究的啟動，預計研發費用將與去年基本持平。我們預計稅率約為 17%，這反映了波多黎各稅法和產品結構的變化。

Finally, we expect to grow our non-GAAP earnings per share, with a range of $7.95 to $8.25. This represents growth of approximately 5%. Excluding prior year acquired in-process R&D, adjusted EPS would grow approximately 2%.

最後，我們預計非公認會計準則每股收益將成長至 7.95 美元至 8.25 美元之間。這意味著成長率約為 5%。不包括上年度獲得的在研研發，調整後的每股盈餘將成長約 2%。

So before we move over to Q&A, I want to thank our colleagues around the world for the strong performance in 2022. Our strong execution in 2022 and our commitments for 2023 reflects the resiliency of our business and the renewal of our product portfolio. The performance in the year positions us well for long-term growth.

因此，在我們進入問答環節之前，我想感謝我們世界各地的同事在 2022 年的出色表現。今年的表現為我們實現長期成長奠定了良好的基礎。

I'll now turn the call back over to Tim and Giovanni for questions and answers.

現在我將把電話轉回給蒂姆和喬瓦尼來進行問答。

Thanks very much, David. I know it's a very busy schedule today. So we're going to get into the Q&A. If you could keep questions just to one, that would be very helpful. Dennis, could we go to the first question, please?

非常感謝，大衛。我知道今天的日程非常繁忙。接下來我們將進入問答環節。如果您能只提出一個問題，那將會非常有幫助。丹尼斯，我們可以開始第一個問題嗎？

The first question is from the line of Chris Schott with JPMorgan. I'm sorry. It's from the line of Geoff Meacham with Bank of America.

第一個問題來自摩根大通的 Chris Schott。對不起。這是美國銀行的傑夫‧米查姆 (Geoff Meacham) 發來的訊息。

Okay. I'll keep it to one. So, Sotyktu, I realize it's early days in the launch. But what are the opportunities to improve formulary positioning this year as your market share improves? And do the many biosimilars launching this year, Humira as well as -- across the board have an impact on any of these PBM discussions?

好的。我會保留一個。所以，Sotyktu，我意識到現在還處於發布的早期階段。但是，隨著市場佔有率的提高，今年有哪些機會可以改善處方定位？今年推出的眾多生物相似藥，Humira 以及全面上市的藥物是否會對這些 PBM 討論產生影響？

Sure. Thanks for the question, Geoff. This is Chris. I'll take it. So first, we're very happy with the performance of Sotyktu. It's obviously early days, but as is reflected in the remarks that David just had, the reception for the product has been very, very good. The feedback that we're getting on the profile coming from customers is good.

當然。謝謝你的提問，傑夫。這是克里斯。我要買它。首先，我們對 Sotyktu 的表現非常滿意。顯然，現在還為時過早，但正如大衛剛才的評論所反映的那樣，該產品的反應非常非常好。我們從客戶那裡得到的關於該資料的反饋很好。

We now have over 2,000 scripts as of the end of November our market share for the oral market in moderate-to-severe psoriasis is roughly 35% for new products. And it's roughly 12% if you look at the overall market, and that's just after 2 full months of launch.

截至 11 月底，我們目前擁有超過 2,000 種處方，在中度至重度牛皮癬口服藥物市場，新產品的市佔率約為 35%。如果從整體市場來看，這一比例大約是 12%，而且這僅僅是在推出整整 2 個月之後。

So very happy with what we're seeing in terms of the momentum coming out of Q4. And as it relates to whether we can accelerate the access position, I think the way we would characterize it is the base case continues to be 2024 for moving into a better access position. That said, we're doing everything we can to possibly accelerate that. We're obviously having good discussions with payers. And the strategy that we have for potentially accelerating that remains unchanged, which is continue to drive demand as quickly as possible for this product. And the good news is we have the profile, and we're seeing the feedback from customers that we think will enable us to do that.

我們對第四季度的勢頭感到非常高興。至於我們是否能夠加速訪問位置，我認為我們對其的描述是，基本情況仍然是 2024 年，以進入更好的訪問位置。話雖如此，我們正在盡一切努力加速這一進程。我們顯然正在與付款人進行良好的討論。我們潛在加速這一進程的策略保持不變，那就是繼續盡快推動對該產品的需求。好消息是我們有資料，我們看到了客戶的回饋，我們認為這將使我們能夠做到這一點。

As for the impact of biosimilars, obviously, this is a dynamic environment. And you've seen a number of movements just in the last few weeks. What I would say is that our approach to gaining access really doesn't evolve based on what we know about biosimilars. We think 2023 is going to be a transition year for biosimilars. Clearly, the strategies of companies and PBMs will continue to evolve. So it's something we'll stay on top of. But as we said right now, certainly, the strategy that we have for Sotyktu doesn't change.

至於生物相似藥的影響，顯然，這是一個動態的環境。僅在過去幾週，您就已經看到了許多動向。我想說的是，我們獲取生物相似藥的方法實際上並不是基於我們對生物相似藥的了解而發展的。我們認為 2023 年將成為生物相似藥的過渡年。顯然，公司和 PBM 的策略將繼續發展。因此我們會密切關注此事。但正如我們現在所說的，我們對 Sotyktu 的策略當然不會改變。

The next question is from the line of Chris Shibutani with Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

With Camzyos, that progress of rolling that out, you have previously talked about the different mix of centers of excellence, and you gave us a patient number. Can you give us a sense for what the relative distribution is of those larger centers versus perhaps maybe smaller practices? Are you seeing momentum with the setup of certifications and essentially the patients flow that you are hoping for at the pace so far?

關於 Camzyos 的推出進展，您之前曾談到過不同卓越中心的組合，並且給了我們一個患者編號。您能否向我們介紹一下這些大型中心與小型診所的相對分佈？您是否看到了認證設定方面的發展勢頭，並且基本上看到了您所希望的患者流量到目前為止的速度？

Sure. We're seeing a nice acceleration of both patient and physician dynamics for Camzyos. As I think David mentioned, we now have over 1,800 patients who have been prescribed. Importantly, we're seeing good and increasing conversion of those scripts to commercial drug. You may recall that in the third quarter, we talked about 30% of scripts that converted over to commercial drug. In Q4, that was 50%. So we're gaining momentum there.

當然。我們看到 Camzyos 的患者和醫生動態都得到了良好的加速。正如 David 所說，我們現在有超過 1,800 名患者接受了處方。重要的是，我們看到這些處方藥轉化為商業藥物的情況良好且不斷增加。您可能還記得，在第三季度，我們討論了 30% 的處方轉化為商業藥物。在第四季度，這一比例為 50%。因此，我們在那裡獲得了發展動力。

And the feedback that we're getting from the centers of excellence continues to be very strong. And so we've seen a nice pickup. And what I would say is that, that pickup has accelerated over the course of the fourth quarter. Recall that we are targeting approximately 500 accounts nationally. Those accounts account for roughly 60% of the overall patient volume.

我們從卓越中心獲得的回饋持續非常強烈。所以我們看到了不錯的回升。我想說的是，這種成長在第四季有所加速。回想一下，我們的目標是全國範圍內大約 500 個帳戶。這些帳戶約佔總患者數量的 60%。

And what we've seen over the last quarter is a nice acceleration in the use of Camzyos in those accounts. And importantly, some of the slower accounts that we have been focused on continue to build the infrastructure necessary to get patients on therapy. And so we've seen a nice acceleration with those specific accounts as well. So overall, we feel like we're making good progress as we exit 2022.

我們在上個季度看到這些帳號中 Camzyos 的使用量顯著加速。重要的是，我們一直關注的一些較慢的帳戶繼續建立讓患者接受治療所需的基礎設施。因此我們也看到這些特定帳戶的成長勢頭良好。因此總體而言，我們感覺在 2022 年即將結束時我們正在取得良好的進展。

The next question is from the line of Chris Schott with JPMorgan.

下一個問題來自摩根大通的 Chris Schott。

Just going back to Sotyktu. Does the mild to moderate Otezla label represent a hurdle at all for Sotyktu as you think about competing for frontline share. Obviously, you're seeing some now, but is that a hurdle you guys think about?

剛剛回到索特克圖。當您考慮爭奪一線市場份額時，輕度至中度的 Otezla 標籤是否會對 Sotyktu 構成障礙？顯然，您現在已經看到了一些，但這是您所認為的障礙嗎？

And just maybe I'm going to slip a really quick second one in. Eliquis, you saw favorable gross-to-net in most of the quarters in 2022. Does that continue in '23? Or should we think of growth this year, maybe more aligned with volume growth?

也許我會很快再問第二個問題。或者我們應該考慮今年的成長，也許更符合銷量成長？

Sure. This is Chris. I'll take both of those. Thanks for the questions, Chris. With respect to Sotyktu, we don't see that the Otezla broader market going into the mild category has an impact on us. And in fact, what we're seeing is very strong momentum with Sotyktu in moderate to severe patients. When we talk to customers, what we hear from them, there's excitement to use the product in the full spectrum of our label, which includes not only the severe patients, but importantly, those moderate patients.

當然。這是克里斯。我都要這兩個。謝謝你的提問，克里斯。就 Sotyktu 而言，我們認為 Otezla 進入溫和類別的大盤不會對我們產生影響。事實上，我們看到 Sotyktu 在治療中度至重度患者方面表現出非常強勁的勢頭。當我們與客戶交談時，我們從他們那裡聽到的是，他們很高興在我們的標籤的全部範圍內使用該產品，這不僅包括重症患者，而且重要的是，包括那些中度患者。

And then if you look at the uptake that we're seeing so far, it's reflective of the fact that physicians are going to be willing to use it, really both in moderate to severe. So given the fact that we have 2 Phase III studies that clearly show superiority across that patient population relative to Otezla, we don't see that being a particular barrier with respect to how we think about the uptake of the product.

如果你看看我們目前看到的接受度，它反映了一個事實，即醫生都願意使用它，無論是中度還是重度。因此，鑑於我們已開展兩項 III 期研究，清楚表明該藥物在整個患者群體中相對於 Otezla 具有優勢，我們並不認為這會成為我們對該產品的接受度考慮的特殊障礙。

As for gross-to-net for Eliquis, for 2022, as you know, we did see some favorability due to mainly the source of business and channel mix. But as you well know, this space is a very competitive space. It's heavily managed. So we don't see gross-to-net favorability as we look forward. There will continue to be variability across quarters. As we've talked about many times in the past, you do see late year seasonality with a product like Eliquis and gross-to-net. But on a forward-looking basis, we don't see favorability with gross-to-net with this product.

至於 Eliquis 的 2022 年毛利與淨利，如您所知，我們確實看到了一些有利因素，這主要歸因於業務來源和通路組合。但如你們所知，這個領域競爭非常激烈。它的管理十分嚴格。因此，展望未來，我們並不認為總利潤與淨利潤之間有有利關係。各季度之間仍會存在差異。正如我們過去多次談到的那樣，您確實會看到 Eliquis 等產品和毛利與淨利之間的價格關係在年底出現季節性。但從前瞻性的角度來看，我們並不認為該產品的毛利與淨利比率有利。

The next question is from the line of Seamus Fernandez with Guggenheim.

下一個問題來自古根漢的 Seamus Fernandez。

So my question actually is on IRA and the drugs that are potentially going to be selected for negotiation towards the end of this year. Just wondering how Bristol is going to manage that situation in particular?

所以我的問題實際上是關於 IRA 和今年年底可能被選中進行談判的藥物。只是想知道布里斯托爾將如何具體處理這種情況？

I know that you do have patent expirations that will limit the impact there. But if that is starting in 2026, given Bristol's current product portfolio, Eliquis, one of the top players there. Just interested to know what it is that you feel Bristol can do to temper the impact there? And then also a sort of separate, but related question on IRA.

我知道你們的專利確實已經到期，這會限制其影響。但如果從 2026 年開始，考慮到布里斯托爾目前的產品組合，Eliquis 是其中的頂尖參與者之一。我只是想知道您認為布里斯托爾可以做些什麼來緩和那裡的影響？然後還有一個關於 IRA 的獨立但相關的問題。

We're seeing the sort of free drug launches that are running for at least a full year and maybe not purely free drug, but substantially aided. Trying to just get a better understanding, particularly for oral, it's starting to look like the life cycle there is starting to get truncated to 6 to 7 years. Wondering if you feel comfortable or even confident that there'll be a better alignment of the oral incentives versus biologic incentives inside IRA as well?

我們看到免費藥品的推出至少持續了一年，也許不是純粹的免費藥品，但卻提供了實質的幫助。試圖更好地理解，特別是對於口語來說，它的生命週期似乎開始縮短到 6 到 7 年。想知道您是否感到放心甚至有信心 IRA 內部的口服激勵措施與生物激勵措施也會有更好的結合？

Thanks, Seamus. This is Giovanni. I'll take the question, and I'll ask Chris to comment on your second question about the free goods strategies. So I think when you look at IRA, similar to the discussion we've had before, I would say there is a lot that we still don't know.

謝謝，西莫斯。這是喬瓦尼。我來回答這個問題，並請克里斯對你關於免費商品策略的第二個問題發表評論。因此我認為當你審視 IRA 時，與我們之前討論的類似，我會說還有很多我們不知道的事情。

As you know, CMS is working through the procedural aspects of implementing the legislation and of course, over the course of this year, we'll learn much more. Now when you look at your question about BMS. So first of all, we know that we do not see an impact from IRA until 2026 when some of the government price setting starts. And you are right that it is possible that Eliquis is impacted in 2026. So of course, we need to learn more in order to understand what the degree of impact may be. I'll just remind you that while we book 100% of the revenue for Eliquis, we split, obviously, the profit with Pfizer. So in many ways, it is an important brand, but it's a smaller brand in terms of determining our earnings trajectory versus what you would think about the revenue line.

如您所知，CMS 正在努力落實該立法的程序方面，當然，今年我們將學到更多。現在，當您查看有關 BMS 的問題時。首先，我們知道，直到 2026 年政府開始製定部分價格後，我們才會看到 IRA 的影響。您說得對，Eliquis 有可能在 2026 年受到影響。我只是想提醒你，雖然我們為 Eliquis 預訂了 100% 的收入，但我們顯然與輝瑞分割利潤。因此，從很多方面來看，它是一個重要的品牌，但從決定我們的獲利軌跡而非你所認為的收入線來看，它是一個較小的品牌。

Now what can we do to continue to grow the company through the execution and implementation of IRA. In many ways, it's exactly what we are doing is advancing new medicines to the market in order to accelerate the renewal of our portfolio. So when you look at 2026, given our expectations that new launch brands will be $10 billion to $13 billion in sales. I would say there will be a very dynamic, young portfolio that will drive the company growth for the second half of the year. And of course, those products will have been launched very recently and therefore, won't be a candidate to government by setting for a while.

現在我們可以做些什麼來透過執行和實施 IRA 來繼續發展公司？從很多方面來看，我們正在做的事情就是將新藥推向市場，以加速我們產品組合的更新。因此，展望 2026 年，我們預期新推出的品牌的銷售額將達到 100 億至 130 億美元。我想說，一個非常有活力的年輕投資組合將會推動公司今年下半年的成長。當然，這些產品都是最近才推出的，因此，暫時還不能成為政府的候選產品。

Now the last comment that I would make is, you are right about the challenges associated with the diverging natives as you refer to them, for the 9 years for oral, 13-year for biologics. We obviously are not pleased with that because the science is going very much in terms of enabling us to deliver -- to develop more and more molecules. But obviously, any change there would require legislative changes. Chris, do you want to comment on the launch of dynamics?

現在我要說的最後一點是，您關於不同本土藥物所帶來的挑戰的說法是正確的，口服藥物需要 9 年，生物製劑需要 13 年。我們顯然對此並不滿意，因為科學正在幫助我們開發越來越多的分子。但顯然，任何改變都需要立法改變。克里斯，你想對動態的發布發表評論嗎？

Sure. Seamus, it's an interesting question on the role that free drug programs play in light of IRAs. As I think most of you know, free drug programs are typical, particularly in markets where rebates require that you have a transition period, particularly for new products to make their way into a more favorable access position.

當然。謝默斯，免費藥物計劃在 IRA 背景下發揮的作用是一個有趣的問題。我想大多數人都知道，免費藥品計劃很常見，特別是在回扣需要過渡期的市場，特別是對於新產品進入更有利的准入地位而言。

Now there's a dynamic there in that those free drug programs are typically targeted to commercial payers. I mean, commercial patients and IRA, of course, is focused on Medicare. That dynamic notwithstanding, I think that you're right, though, that to the extent that free drugs and free-drug programs play out for extended periods, it could have a negative impact when you look at the IRA restrictions and price setting coming in, in 9 years.

現在的動態是，這些免費藥物計劃通常針對商業付款人。我的意思是，商業患者和 IRA 當然專注於醫療保險。儘管存在這種動態，但我認為你是對的，如果免費藥物和免費藥物計劃長期實施，當你看到 9 年後 IRA 的限制和價格製定時，它可能會產生負面影響。

I think what that reinforces for us though is the importance of very strong commercial execution because clearly, what you want to do is transition from free drugs into a more favorable access position as quickly as possible. And so as we just discussed, for a product like Sotyktu, that's going to continue to be our focus. But I think it's a very important question. It's something that we're going to have to continue to monitor as we learn more about the rollout of IRA.

我認為這對我們來說更加強調了強大的商業執行力的重要性，因為很明顯，你想要做的是盡快從免費藥品過渡到更有利的獲取地位。正如我們剛才討論的那樣，對於像 Sotyktu 這樣的產品，這將繼續是我們的重點。但我認為這是一個非常重要的問題。隨著我們進一步了解 IRA 的推出情況，我們將不得不繼續關注這一點。

The next question is from the line of Steve Scala with Cowen.

下一個問題來自 Cowen 的 Steve Scala。

We noted that Bristol initiated a milvexian SSP Phase III trial with primary completion in November 2026 and that additional Phase IIIs will be started in the first half of this year. But Bayer's studies are expected to read out a full year earlier. Is this consistent with your perception that Bristol is a year behind Bayer? I should add that you are not first with Eliquis and ended up dominating, but let me -- let you answer the question.

我們注意到，布里斯托啟動了 milvexian SSP 第三階段試驗，並於 2026 年 11 月完成初步研究，並且額外的第三階段試驗將於今年上半年啟動。但拜耳的研究預計將提前一年完成。這與您認為布里斯托落後拜耳一年的看法一致嗎？我應該補充一點，你並不是第一個推出 Eliquis 並最終佔據主導地位，但讓我——讓你回答這個問題。

Samit here. Look, we planned the studies, and we put a timeline with those studies in terms of the enrollment. And then of course, these are event-driven trials. So we'll have to wait for the events to happen before we read out and report the results. So we have to take all of those into accounts, but of course, the clinical trials we can impact them by looking at what the enrollment rates are and how these trials are enrolled.

這裡是薩米特 (Samit)。你看，我們計劃了這些研究，並在招生方面為這些研究制定了時間表。當然，這些都是事件驅動的試驗。因此我們必須等待事件發生後才能宣讀並報告結果。因此，我們必須將所有這些都考慮在內，當然，我們可以透過查看入組率以及這些試驗的入組方式來對臨床試驗產生影響。

So I think what you see on ClinicalTrials.gov is our guesstimate of when the trials are going to be reading out. It is through that we might be reading out earlier. It is possible our competitors will be reading out later. But these are early days, and we'll update you as the trial progresses if the timelines do shift.

所以我認為您在 ClinicalTrials.gov 上看到的是我們對試驗結果公佈時間的估計。透過這種方式我們也許可以更早讀出來。我們的競爭對手有可能稍後會唸出來。但現在還為時過早，如果時間表確實發生變化，我們會隨著審判的進展向您通報。

The next question is from the line of Tim Anderson with Wolfe Research.

下一個問題來自 Wolfe Research 的 Tim Anderson。

A few questions back on Sotyktu. Can you just quantify where you are on market access in '22 in terms of number of lives covered? And where you do have access, are there any step that is requiring Otezla first? And then on your BRIDGE program, will that last all the way through '23? Or will you begin to phase it out before year-end?

關於 Sotyktu 的幾個問題。您能否以涵蓋的人數來量化您在 2022 年的市場准入情況？在您可以訪問的地方，是否有任何步驟需要先使用 Otezla？那麼，您的 BRIDGE 計畫會持續到 23 年嗎？或者你會在年底前開始逐步淘汰它嗎？

So with respect to market access, we think we have about 10% of patients who are in plans that have open or preferred access. And obviously, that's going to continue to increase as we continue to engage with payers. And as we said, our base case for a much more favorable access position at large across the major PBMs is for 2024, but we're doing everything we can to accelerate that.

因此就市場准入而言，我們認為大約有 10% 的患者參與了開放或優先准入計劃。顯然，隨著我們繼續與付款人合作，這一數字將繼續增加。正如我們所說，我們的基本情況是 2024 年在主要 PBM 中獲得更有利的訪問地位，但我們正在盡一切努力來加速這一進程。

As for the BRIDGE programs, BRIDGE programs are typical in this market, and I think we would typically think about keeping those BRIDGE programs open until we find that we are in a position where we've got the volume to negotiate a much faster access or more favorable access with the big PBMs.

至於 BRIDGE 計劃，BRIDGE 計劃在這個市場中很典型，我認為我們通常會考慮保持這些 BRIDGE 計劃開放，直到我們發現我們有足夠的數量來與大型 PBM 協商更快的訪問或更有利的訪問。

The nice thing that we're seeing, Tim, with Sotyktu is that the vast majority of patients are going into our hub. What that enables us to do is monitor the status of those patients with respect to formulary positioning. And so even if that BRIDGE program is open, we have the ability to transition those patients to commercial drug, the moment we certify that their plans are able to take them on commercial drug.

提姆，我們在 Sotyktu 看到的好消息是，絕大多數患者都進入了我們的中心。這使我們能夠監控這些患者在處方定位方面的狀況。因此，即使 BRIDGE 計劃開放，只要我們證明他們的計劃能夠讓他們使用商業藥物，我們就有能力將這些患者轉為使用商業藥物。

And so it's a more dynamic process than might be indicated just in the discussions that we've had. In fact, we have the ability to look at this on a more real-time basis. But we do anticipate that those BRIDGE programs will remain open certainly as we get into 2024.

因此，這是一個比我們討論中所顯示的更動態的過程。事實上，我們有能力以更即時的方式看待這個問題。但我們確實預計，到 2024 年，這些 BRIDGE 計畫肯定會繼續開放。

The next question is from the line of Evan Seigerman with BMO Capital Markets.

下一個問題來自 BMO 資本市場 (BMO Capital Markets) 的 Evan Seigerman。

On Abecma, you went from kind of struggling to meet patient demand in early 2022 to now expanding into earlier lines of therapy. Now how should we think about bridging this gap, really I'm talking about expanding capacity and when we could potentially see more slots come along for both your cell therapies?

關於 Abecma，你們從 2022 年初努力滿足患者需求，到現在擴展到更早期的治療方法。現在我們應該如何考慮彌合這一差距，實際上我在談論擴大產能，以及何時我們有可能看到更多的細胞療法出現？

Yes. Evan, maybe I'll take that one. This is Chris. So we're actually quite happy with the expansion of capacity that we continue to see with Abecma and actually, we saw with both products in the fourth quarter. You may recall that for Breyanzi, we had anticipated the expansion of capacity would wait until we got into this year. We were very happy to see that expansion be accelerated into Q4.

是的。埃文，也許我會選擇這個。這是克里斯。因此，我們對 Abecma 產能的持續擴張感到非常高興，實際上，我們在第四季度就看到了這兩種產品的產能擴張。您可能還記得，對於 Breyanzi，我們預計產能擴張要等到今年。我們非常高興地看到擴張在第四季加速進行。

So I think that as we look forward to this year, we continue to see an expansion of capacity for both cell products, cell therapy products, and that's certainly true with Abecma. And I would say the other thing to keep in mind is we thought about manufacturing, which is going to continue to be an area of focus for us for cell therapy is we have a threefold strategy.

因此，我認為，展望今年，我們將繼續看到細胞產品和細胞治療產品的產能擴大，而 Abecma 的情況也是如此。我想說的另一件要記住的事情是我們考慮了製造業，這將繼續成為我們細胞療法關注的領域，我們有一個三重策略。

First, we continue to stay focused on manufacturing success rates. That's one of the more important elements that frankly affect all the cell therapy products. These are complex drugs, they're living products and you have to stay focused on your manufacturing success rate.

首先，我們繼續關注製造成功率。坦白說，這是影響所有細胞治療產品的更重要的因素之一。這些都是複雜的藥物，它們是活產品，你必須專注於製造成功率。

Second, we've talked at length about vector supply, and we obviously have a number of strategies in play from dual sourcing to increasing the number of suites and ultimately switching to a next-generation suspension vector on that front.

其次，我們已經詳細討論了向量供應，顯然我們採取了多種策略，從雙重來源到增加套件數量，最終轉向下一代懸掛向量。

And then finally, drug product. And there, it's mainly about bringing additional manufacturing sites online, and we've discussed previously our efforts in Devens, Massachusetts enlightened to do just that. So what I would say sort of leveling it up is that manufacturing has to continue to be an area of focus for us. We've got good strategies in place, and we've seen those strategies play out with expanded capacity, not only in Q4 but we anticipate through the remainder of this year.

最後是藥品。我們的主要任務是讓更多的生產基地上線，我們之前已經討論過我們在馬薩諸塞州德文斯的努力就是為了實現這一目標。因此，我想說的是，製造業必須繼續成為我們關注的領域。我們已經制定了良好的策略，我們看到這些策略在擴大產能方面發揮了作用，不僅在第四季度，而且我們預計還將持續今年剩餘時間。

The next question is from the line of Terence Flynn with Morgan Stanley.

下一個問題來自摩根士丹利的特倫斯·弗林（Terence Flynn）。

David, probably for you. Just thinking about the guidance, OpEx, you've guided a low single-digit decline this year, which offsets some of the gross margin pressure. And R&D, you're holding flat. So it looks like most of the decline is going to come on the SG&A side. So just as we look into 2024, I guess we're anticipating additional gross margin pressure given Revlimid rolling off more fully. How should we think about expenses and margins as we think about the cadence into '24?

大衛，也許對你來說是這樣。僅考慮指導方針，營運支出，您指導今年的降幅將達到個位數以下，這抵消了部分毛利率壓力。而研發則維持不變。因此，看起來大部分下降將發生在銷售、一般和行政費用方面。因此，展望 2024 年，我猜我們預計，由於 Revlimid 的全面推出，毛利率將面臨額外的壓力。當我們考慮24年的節奏時，我們應該如何考慮費用和利潤？

Terence, thank you for the question. And you're right as it relates to gross margins, we do anticipate them coming down. And last year was in line with expectations as what we're guiding this year at that 77% due to that product mix as revenue declines.

特倫斯，謝謝你的提問。您說得對，就毛利率而言，我們確實預期毛利率會下降。去年的銷售額與預期相符，由於產品組合原因，我們預計今年的銷售額將達到 77%，而收入則有所下降。

As far as OpEx is concerned, we continue to find efficiencies, operational efficiencies. We learned a lot through COVID, with digital technologies, particularly on how we're engaging with health care professionals. But also on top of that, reallocating resources from the mature brands to our launch products, making sure they're fully funded, we've been able to do that very effectively.

就營運支出 (OpEx) 而言，我們不斷尋求效率，即營運效率。我們透過 COVID 學到了很多東西，包括數位技術，特別是如何與醫療保健專業人士互動。但除此之外，我們將資源從成熟品牌重新分配到我們推出的產品上，確保它們獲得充足的資金，我們已經能夠非常有效地做到這一點。

From an R&D perspective, you may recall, as we talked about the levels of R&D spend, it's really driven by our portfolio. That has the single biggest impact on the level of R&D spend, and we just launched 9 new products. So we had many late-stage programs coming offline. We have some new ones coming online, but some of those are through partnerships. I think milvexian is a great example of that, where we have several Phase III programs that are going to be beginning, but that's shared with our -- those costs are shared with our partners.

從研發的角度來看，您可能還記得，正如我們討論的研發支出水準一樣，它實際上是由我們的投資組合所驅動的。這對研發支出水準產生了最大的影響，我們剛推出了 9 款新產品。因此，我們有許多後期專案下線。我們有一些新的產品上線，但其中一些是透過合作實現的。我認為 milvexian 是一個很好的例子，我們有幾個即將開始的第三階段項目，但這些項目的成本是與我們的合作夥伴分擔的。

So that's why we believe, as we look at our business this year, a low single-digit decline in our overall operating expenses is what we're anticipating. But we feel very confident even with the step down in gross margin. As we look at our base, continue to grow the top line faster than our expense base that gives us the flexibility to maintain those operating margins above 40%.

因此，我們相信，當我們回顧今年的業務時，我們預計整體營運費用將出現個位數的低下降。但即使毛利率下降，我們仍然非常有信心。當我們審視我們的基礎時，我們會發現營收成長速度持續快於支出基礎，這使我們能夠靈活地將營業利潤率維持在 40% 以上。

The next question is from the line of Mohit Bansal with Wells Fargo.

下一個問題來自富國銀行的 Mohit Bansal。

Maybe if I may ask a little bit more on the guidance side. So from our math, it looks like for in-line products, you are looking at another really good year. So after like 11% growth, we calculate, you're expecting about 8% growth again this year, which seems to be the delta between you and consensus. So could you please talk a little bit about puts and takes there? And where do you see the most robust growth in that in-line portfolio, considering Eliquis OUS challenges there as well?

也許我可以在指導方面多問一些問題。因此，從我們的計算來看，對於線上產品而言，我們將迎來另一個非常好的一年。因此，在實現 11% 的成長後，我們計算出，您預計今年的成長幅度將再次達到 8% 左右，這似乎是您與普遍預期之間的差距。那麼您可以稍微談談那裡的放置和獲取嗎？考慮到 Eliquis OUS 面臨的挑戰，您認為該產品線投資組合中最強勁的成長點在哪裡？

Yes. Well, thank you for the question. And you're right. We do see multiple drivers for our growth in '23. As I said, overall, 2% growth with our in-line and new product portfolio, offsetting the declines in our -- in Revlimid and the LOEs. And that's really coming across as we think about the in line. And as we talked about before, we had really strong double-digit growth on Eliquis this past year. We continue to see growth despite some of the headwinds that we see in Europe, good strong growth in the U.S. and Opdivo, Yervoy with our additional tumor indications and adjuvant setting. We continue to see good growth in lung as well as in gastric cancers and continue to see very strong growth continuing on our IO franchise.

是的。嗯，謝謝你的提問。你說得對。我們確實看到了推動我們23年成長的多個驅動因素。正如我所說，總體而言，我們的線上和新產品組合成長了 2%，抵消了 Revlimid 和 LOE 的下滑。當我們思考排隊時，這一點確實出現了。正如我們之前談到的，去年 Eliquis 實現了強勁的兩位數成長。儘管我們在歐洲看到了一些阻力，但我們仍然看到成長，而美國以及 Opdivo 和 Yervoy 都保持了強勁的成長勢頭，因為我們有額外的腫瘤適應症和輔助治療。我們繼續看到肺癌和胃癌的良好成長，並且繼續看到我們的IO特許經營繼續保持非常強勁的成長。

And then the new products, remember, that's a significant growth driver. As I talked about in my earlier remarks, and that doubled last year. And as we said, we see that continuing into this year. So between the in-line business as well as that new product momentum that we have as we exited last year and the guidance we're providing this year, we have multiple ways to continue to grow, and we're very confident in our ability to do that this year.

然後是新產品，請記住，這是一個重要的成長動力。正如我在之前的評論中提到的，去年這個數字翻了一番。正如我們所說，我們認為這種情況將持續到今年。因此，在我們去年退出時擁有的線上業務和新產品勢頭以及我們今年提供的指導之間，我們有多種方式可以繼續成長，我們對今年做到這一點的能力非常有信心。

Your next question is from the line of Carter Gould with Barclays.

您的下一個問題來自巴克萊銀行的卡特古爾德。

Maybe you focus on one of those launch products with Reblozyl here. You alluded to some duration growth. Would love any additional color you can provide there? And then as you think about COMMANDS, how should we think about the Stage 8 to filing and when we might see that data presented? Is that something we might have to wait to, say, late June 4? Or is there the opportunity to potentially share that data ahead of that?

也許您關注的是與 Reblozyl 合作推出的其中一款產品。您提到了一些持續時間的成長。您是否願意提供其他顏色？然後，當您考慮命令時，我們應該如何考慮第 8 階段的歸檔以及何時我們可以看到所呈現的資料？我們是不是要等到 6 月 4 日下旬才能看到這個消息？或者是否有機會在此之前潛在地共享這些數據？

Yes. Maybe I'll start and then switch it over to Samit for your questions on COMMANDS. So with respect to Reblozyl, yes, we continue to see good acquisition of new patients on Reblozyl out of -- coming out of the fourth quarter. And certainly, we would expect to see that continue into this year.

是的。也許我會開始，然後將其轉交給 Samit 來回答您關於命令的問題。因此，就 Reblozyl 而言，是的，我們繼續看到 Reblozyl 在第四季度獲得新患者的良好成長。當然，我們預計這種情況將持續到今年。

But as you note, where we see the potential for the most significant growth with this product is really -- first is increasing dosing and administration and ensuring that we've got the right titration of patients. We have seen some improvements in that regard over the last year.

但正如您所說，我們認為這款產品最顯著的成長潛力實際上在於——首先是增加劑量和給藥方式，並確保我們對患者進行正確的滴定。過去的一年我們在這方面看到了一些進步。

In fact, duration of therapy is up 6% in 2022 versus 2021, and we would expect to continue to see, particularly as patients titrate up over time, consistent with the MEDALIST study that, that duration of therapy would continue to increase this year.

事實上，2022 年的治療持續時間與 2021 年相比增加了 6%，我們預計這種情況將繼續發生，特別是隨著患者的治療時間隨著時間的推移而增加，與 MEDALIST 的研究一致，今年的治療持續時間將繼續增加。

And then the second big area of focus that we have is getting those patients who are no longer responding to ESAs in the first-line setting to move on to Reblozyl. That's been a big area of focus for us.

我們關注的第二個重點領域是讓那些不再對第一線治療的 ESA 有反應的患者轉而使用 Reblozyl。這是我們關注的一個重點領域。

And again, here, two, we've made good progress. The time on ESAs has decreased since our approval from roughly 18 months to now roughly 11 months.

再次，在這一點上，我們取得了良好的進展。自從我們批准以來，ESA 的時間已經從大約 18 個月減少到現在的大約 11 個月。

And so those are the 2 big dimensions that we have as a focus in 2023. And then obviously, the COMMANDS study provides the next large catalyst for growth. And we think that, that indication we'll roughly double the opportunity that we have with Reblozyl. But in terms of timing, I think Samit can speak to that.

因此，這些是我們在 2023 年關注的兩個大面向。我們認為，這表明我們擁有的 Reblozyl 機會將大約增加一倍。但就時間而言，我認為薩米特可以談談這一點。

Thank you, Chris, and thanks, Carter, for the question as well. So we don't have the specifics of our conference right now, where we will be able to share the data. But certainly, we will confirm that as information becomes available.

謝謝克里斯，也謝謝卡特提出這個問題。因此，我們目前還沒有關於會議的具體細節，無法分享數據。當然，一旦有資訊可用，我們將確認這一點。

In terms of the filing, again, we do not comment on that until we have -- we release -- we do a press release after the file is accepted. But certainly pleased with the data, as Chris just mentioned, COMMANDS is an important study for moving our Reblozyl to the front line where we compared against an active control of ESAs and shown the superiority.

關於備案，我們再次聲明，我們不會對此發表評論，直到我們發布——文件被接受後，我們會發布新聞稿。但確實對數據感到滿意，正如克里斯剛才提到的，COMMANDS 是一項重要的研究，它對於將我們的 Reblozyl 推向前線，我們與 ESA 的主動控制進行了比較並顯示出優越性。

The next question is from the line of Matt Phipps with William Blair.

下一個問題來自威廉布萊爾 (William Blair) 的馬特菲普斯 (Matt Phipps)。

You noted in the slides the decision not to move Cendakimab into forward in atopic derm. Is that something specific from the product profile in the Phase II? Or that could maybe read through to the ongoing EoE trial? Or is it just the competitive dynamics in atopic dermatitis?

您在幻燈片中註意到了不將 Cendakimab 移至特應性皮膚病學領域的決定。這是第二階段產品概況中的具體內容嗎？或者也許可以讀到正在進行的 EoE 審判？還是這只是異位性皮膚炎中的競爭動態？

Yes, sure, Matt. I can take that question, Samit here. Thank you for that. Look, remember, we have always said that as we move our programs forward, we always look at the data and we want to see the differentiation of that data and then, of course, look at the landscape and the competitive dynamics as well. In atopic dermatitis, there are several therapies that have recently become available for patients, and they're very effective. And so we had set our threshold quite high in terms of making that difference for the patients for atopic dermatitis.

是的，當然，馬特。我可以回答這個問題，薩米特。謝謝你。記住，我們一直說，在推進專案的過程中，我們總是關注數據，我們希望看到數據的差異化，然後，當然，也要關注格局和競爭動態。對於異位性皮膚炎，最近有幾種可供患者使用的療法，而且非常有效。因此，我們為異位性皮膚炎患者設定的治療門檻相當高。

So we have seen the data. We do meet the primary endpoint, but we don't think that it has a competitive advantage over what is available to the patients at this time. And therefore, we are not moving into the registration trials. But it has nothing to do with what we saw for cendakimab in Eosinophilic Esophagitis, where we not only saw a change in the eosinophil infiltration, but also the dynamics in terms of the outcomes of patients for their dysphagia as well as the fibrosis in the Phase II study. And so that study continues and certainly, we'll share the results when the study is completed.

所以我們已經看到了數據。我們確實達到了主要終點，但我們認為它與目前患者可用的產品相比並不具有競爭優勢。因此，我們不會進入註冊試驗階段。但這與我們在嗜酸性食道炎中看到的 cendakimab 情況無關，我們不僅看到了嗜酸性粒細胞浸潤的變化，還看到了患者吞嚥困難和 II 期研究中纖維化結果的動態變化。這項研究將繼續進行，當然，研究完成後我們將分享結果。

Your next question is from the line of Robyn Karnauskas with Truist Securities.

您的下一個問題來自 Truist Securities 的 Robyn Karnauskas。

Great. Thank you for the question. So you have TYK2 in lupus, Sotyktu in lupus. There's going to be a Phase III reading out with Pfizer and JAK plus TYK2 later this year. Maybe frame it on if that trial fails, like what's your thoughts on the biology and how you'll think about potential success for TYK2?

偉大的。感謝您的提問。因此，狼瘡患者有 TYK2，狼瘡患者有 Sotyktu。今年晚些時候，輝瑞將與 JAK 和 TYK2 合作進行第三階段試驗。也許可以設想一下，如果那次試驗失敗了，您對生物學有什麼看法，以及您如何看待 TYK2 的潛在成功？

And then a food question, if it succeeds, how do we think about from a biology standpoint, if you know anything about how much value adding JAK on top of a TYK2 might be for lupus? I know it could influence the safety profile, but anything you could give us on efficacy, it would be great.

然後是關於食物的問題，如果它成功了，我們從生物學的角度該如何思考，您是否知道在 TYK2 之上添加 JAK 對狼瘡有多大價值？我知道它可能會影響安全性，但如果您能就功效提供任何信息，那就太好了。

Maybe I can take that again. This is Samit. Thank you for the question. If you think about it, today, there is no JAK inhibitor approved for treatment of patients with psoriasis. We demonstrated the benefits of a TYK2 inhibitor, which has very specific downstream effects on IL-12, IL-23 and interferon, which, of course, is important. And throughout the last year or maybe even more, we've been answering that question of differentiation and protecting from a safety perspective, the profile of a TYK2 inhibitor versus a JAK inhibitor.

也許我可以再接受一次。這是薩米特。感謝您的提問。如果你仔細想想，目前還沒有一種JAK抑制劑被批准用於治療牛皮癬患者。我們展示了 TYK2 抑制劑的益處，它對 IL-12、IL-23 和乾擾素具有非常特殊的下游效應，這當然很重要。在過去一年甚至更長的時間裡，我們一直在回答從安全角度進行區分和保護的問題，即 TYK2 抑制劑與 JAK 抑制劑的區別。

So if you just move that fast forward now and think about it that for a patient population for whom we've just shown a superiority versus the prior standard of care that was being used in the oral setting, we've shown 2 trials with that superiority. We've got the data in the Phase II setting for psoriatic arthritis as well as SLE, and we are in the Phase III clinical trials for all of these indications.

因此，如果您現在快轉並想一想，對於我們剛剛展示出優於口腔環境中使用的先前護理標準的患者群體，我們已經在 2 項試驗中展示了這種優越性。我們已經獲得了銀屑病關節炎和 SLE 的 II 期臨床試驗數據，並且正在針對所有這些適應症進行 III 期臨床試驗。

So I think the profile of Sotyktu is well set now, I think, and the confidence that we have on the data and the evolution of the data is making it very promising for physicians to prescribe it, as Chris talked about earlier. So we will rely on that information and the evolution of the data for our own molecule.

所以我認為 Sotyktu 的概況現在已經很好了，而且我們對數據和數據發展的信心使得醫生很有希望開出這種藥物，就像克里斯之前談到的。所以我們將依靠這些資訊和數據的演變來研究我們自己的分子。

I cannot speak to what Pfizer will do when their data reads out. But certainly, I'm pretty sure you will all be asking the question, is a JAK inhibitor right thing to do in psoriasis when there are efficacious safe therapies available for these patients.

我無法說出輝瑞公司在數據讀出後會做什麼。但可以肯定的是，我非常肯定你們都會問這個問題，當有針對牛皮癬患者有效安全療法時，使用 JAK 抑制劑是否正確？

The next question is from the line of Olivia Brayer with Cantor Fitzgerald.

下一個問題來自 Cantor Fitzgerald 的 Olivia Brayer。

Chris, maybe one for you. Is there any update on Revlimid sales expectations looking beyond this year? I know you've talked about a $2 billion plus annual decrease in the past. But any changes to your thinking with respect to the revenue run rate there? And then a quick clarifying question on Sotyktu. Where are you guys at with the high-dose program? And could we see that move into any indications beyond UC at some point?

克里斯，也許有一個適合你。今年以後 Revlimid 的銷售預期有什麼改變嗎？我知道您過去曾談到每年減少20多億美元。但是，對於那裡的收入運行率，您的想法有什麼改變嗎？然後快速澄清一個關於 Sotyktu 的問題。你們的高劑量計畫進行到哪一步了？我們是否可以看到這種趨勢在某個時候超越 UC 的任何跡象？

Great. Olivia, it's David Elkins here. I'll take the Revlimid one. Nothing has really changed in our outlook for Revlimid through 2025. We provide our update for this year, that $6.5 billion, which is a $3.5 billion step down given better performance this -- last year in 2022. As we think about '24 and '25, on average, about a $2.5 billion step-down is how we're thinking about it. Chris or Samit?

偉大的。奧莉維亞，我是大衛艾爾金斯。我想要 Revlimid。我們對 Revlimid 到 2025 年的展望並沒有發生任何變化。克里斯還是薩米特？

Actually, thank you, David. So Olivia, certainly, so TYK2 has 2 studies in IBD that are ongoing. One of them using a higher dose in ulcerative colitis. If you recall, we do not have a proof-of-concept in ulcerative colitis or IBD at this time. And the -- one of the hypothesis that we want to test is the higher dose of Sotyktu in IBD or specifically over here in ulcerative colitis.

事實上，謝謝你，大衛。所以奧利維亞，當然，TYK2 在 IBD 方面有 2 項研究正在進行中。其中一種用於治療潰瘍性結腸炎的藥物使用劑量較高。如果你還記得的話，我們目前還沒有關於潰瘍性結腸炎或 IBD 的概念驗證。我們想要驗證的假設之一是，對於 IBD 患者，或特別是潰瘍性結腸炎患者，Sotyktu 的劑量是否較大。

So we are looking forward to seeing the data in the latter part of this year. And dependent on that data dependent on outcome, then we'll be able to formulate the strategies as to how to move forward in IBD and/or other indications at the higher dose.

所以我們期待看到今年下半年的數據。根據結果數據，我們將能夠制定如何以更高劑量治療 IBD 和/或其他適應症的策略。

You recall, though, that we've also tested higher doses in previous trials and other indications, and our safety profile has been maintained in those clinical trials. So we are not necessarily looking forward to any major signals that could arise at the higher dose, but certainly looking for the efficacy signals.

不過，您還記得，我們​​在先前的試驗和其他適應症中也測試過更高的劑量，而我們的安全性在這些臨床試驗中得到了維持。因此，我們不一定期待在較高劑量下出現任何重大訊號，但肯定會尋找療效訊號。

Our next question is from the line of Andrew Baum with Citi.

我們的下一個問題來自花旗的 Andrew Baum。

A couple of questions on your LPA1 antagonist. Can you just remind us when we might see that Phase II data? And also, given the failure of Roche's Pentraxin today, how you're thinking about the Phase III trial design? And then finally, what are the fibrotic indications aside from IPF you are looking at for that drug?

關於 LPA1 拮抗劑，我有幾個問題。您能提醒我們什麼時候可以看到第二階段的數據嗎？此外，鑑於羅氏 Pentraxin 今天的失敗，您如何考慮 III 期試驗設計？最後，除了特發性肺纖維化 (IPF) 以外，您還在研究該藥物的哪些纖維化適應症？

Thank you, Andrew. So LTA1 certainly, we're looking forward to presentation of the data within this year, within the first half of this year. And certainly, as soon as we have confirmation on the conference, we will be able to share that information.

謝謝你，安德魯。因此，LTA1 當然期待在今年，也就是今年上半年內展示數據。當然，一旦我們確認了會議召開，我們將能夠分享該資訊。

We did see the news from the competitive program, as you're referring to Roche that the Phase III trial was stopped. We do see that our data, the Phase II data that we've seen thus far are very strong. We've talked about the patient population with no background standard of care as well as in combination with the background standard of care therapies, and we are pleased with what we've seen. We are in discussions on the appropriateness of the clinical trial design with the regulatory authorities, and you will get to see that as we launch that and as we make that public. So more to follow on that in appropriate time to come. But really pleased with that.

我們確實看到了來自競爭項目的消息，正如您所提到的，羅氏公司的第三階段試驗已經停止。我們確實看到我們的數據，迄今為止看到的第二階段數據非常強勁。我們討論了沒有背景護理標準的患者群體以及結合背景護理標準療法的患者群體，我們對所看到的結果感到滿意。我們正在與監管機構討論臨床試驗設計的適當性，當我們啟動該試驗並公開結果時，您就會看到這一點。因此，我們將在適當的時候繼續關注此事。但我真的對此感到高興。

And the last question that you had on the additional fibrosis programs, we're looking at LPA1 from 2 perspectives right now. One is the IPF program and the other one is the progressive pulmonary fibrosis. But that Phase II data is going to be reading out later this year. So we're looking at those 2 things for now.

您關於額外纖維化項目的最後一個問題，我們目前從兩個角度來看 LPA1。一個是特發性肺纖維化（IPF）項目，另一個是進行性肺纖維化項目。但第二階段的數據將於今年稍後公佈。因此我們現在正在關注這兩件事。

Today's final question will come from the line of Colin Bristow with UBS.

今天的最後一個問題來自瑞銀的科林布里斯托。

Maybe just a couple of very quick pipeline questions. I see you have another TYK2 inhibitor in Phase I. Could you just give us any color on that and how you'd anticipate it differentiating versus the TYK2? And then just another one on 287, you recently terminated Phase 1 development in non-small cell. This is one of our anti-TIGIT. I think you cited safety issues. I was just wondering if you could specifically say what these issues were.

也許只是幾個非常快速的管道問題。我看到您在 I 期臨床試驗中還有另一種 TYK2 抑制劑。然後還有 287 號，您最近終止了非小型基地台第 1 階段的開發。這是我們的反TIGIT措施之一。我認為您提到了安全問題。我只是想知道您是否可以具體說一下這些問題是什麼。

Sure. Thank you. In terms of your first question around the Phase I that is ongoing with the next TYK2 inhibitor. In general, we always have 1 or 2 programs that we look at in terms of having the next generation of molecules in development. And so this is just a phases of development of general pipeline that we have additional TYK2 inhibitor. We also have a CNS penetrant TYK2 inhibitor that is in Phase I. So there is nothing special at this time to talk about. But certainly, as the data arises, as the data evolves, we will be able to share those data in the future.

當然。謝謝。關於您第一個問題，關於下一個 TYK2 抑制劑正在進行的 I 期研究。一般而言，我們總是會考慮 1 或 2 個正在開發中的下一代分子項目。所以這只是我們有附加 TYK2 抑制劑的一般管道開發的一個階段。我們還有一種中樞神經系統滲透性 TYK2 抑制劑，目前正處於 I 期臨床研究階段。但可以肯定的是，隨著數據的出現和發展，我們將來將能夠分享這些數據。

For the TIGIT program, remember, this is a trial that was being conducted in patients with non-small cell lung cancer looking at a combination with nivolumab and ipilimumab. And what we have seen thus far, I'm not going into the specifics because those data will be presented at some future conference, but we do see that there is a toxicity that is observed when combined with dual I-O therapy for this particular TIGIT inhibitor.

對於 TIGIT 計劃，請記住，這是一項針對非小細胞肺癌患者進行的試驗，研究其與 nivolumab 和 ipilimumab 的聯合治療。至於目前我們看到的情況，我不會詳細描述，因為這些數據將在未來的某個會議上公佈，但我們確實看到，當與這種特定的 TIGIT 抑製劑的雙重 I-O 療法相結合時，會出現毒性。

And so more data to come as we get more insights and more specifics on that and then the presentation will be done. But because of those safety reasons, we have decided to terminate this particular trial at this time.

隨著我們獲得更多見解和更多細節，將會有更多的數據，然後演示就會完成。但出於安全原因，我們決定暫時終止此試驗。

Thank you, Samit, and thanks to all of you for your participation. As you've seen, it's an exciting time for the company. We have another important year ahead, lots of things to talk about. But we know it's a very busy morning for all of you. So we're going to end the call here. And as always, please reach out to our team if you have any additional questions. So thanks, everyone, and have a great day. Thank you.

謝謝你，薩米特，也謝謝大家的參與。正如您所看到的，對於公司來說這是一個令人興奮的時刻。我們將迎來重要的一年，有很多事情要談。但我們知道你們所有人今天早上都非常忙碌。所以我們就到此結束通話。像往常一樣，如果您有任何其他問題，請聯絡我們的團隊。謝謝大家，祝大家有個愉快的一天。謝謝。

This does conclude the Bristol-Myers Squibb's Fourth Quarter 2022 Earnings Conference Call. Thank you for your participation. You may now disconnect.

百時美施貴寶 2022 年第四季財報電話會議到此結束。感謝您的參與。您現在可以斷開連線。