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)

早上好。我叫丹尼斯，今天我將擔任你們的會議接線員。此時，我想歡迎大家參加 Bristol-Myers Squibb 2022 年第四季度收益電話會議。 （操作員說明）

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

我現在想將會議轉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，早上好。感謝您今天早上加入我們的 2022 年第四季度財報電話會議。

Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. 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，我們的董事會主席兼首席執行官喬瓦尼·卡福里奧 (Giovanni Caforio) 和我一起發表了準備好的講話；和我們的首席財務官 David Elkins。參加今天電話會議的還有我們的首席商務官 Chris Boerner；和 Samit Hirawat，我們的首席醫療官兼全球藥物開發主管。

As you'll note, we've posted slides to bms.com that you can follow along with for Giovanni and David's remarks.

您會注意到，我們已將幻燈片發佈到 bms.com，您可以跟隨 Giovanni 和 David 的評論。

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，我將閱讀我們的前瞻性聲明。在此次電話會議中，我們將對公司未來的計劃和前景做出某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表明的結果存在重大差異。這些前瞻性陳述代表我們截至今天的估計，不應作為我們對未來任何日期的估計的依據。我們特別聲明不承擔任何更新前瞻性陳述的義務，即使我們的估計發生變化也是如此。

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 GAAP 財務指標，這些指標經過調整以排除某些特定項目。 bms.com 提供了某些非 GAAP 財務指標與最具可比性的 GAAP 指標的對賬。

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

有了這個，我會把它交給喬瓦尼。

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.

謝謝蒂姆，大家早上好。從幻燈片 4 開始。我很高興地報告 Bristol-Myers Squibb 又一個強勁的季度，結束了非常成功的一年。

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 Revlimid 仿製藥的第一年。鑑於此，我可以非常自豪地說，在 2022 年，我們發展了業務並在推進我們的管道方面取得了巨大進展，包括推出 3 種新的一流藥物和將 6 個有前途的項目推進到註冊開發。

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.

雖然 David 稍後會提供有關財務的更多詳細信息，但我會指出一些要點。去年，我們實現了 3% 的收入增長（根據匯率調整）。重要的是，增長是由我們的在線和新產品組合推動的。因此，我很高興地註意到，我們在第四季度實現了這些資產的持續強勁增長，按匯率調整後增長了 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.

我們的收益也有所增長，包括全年 8% 的非 GAAP 每股收益增長。隨著 2023 年的開始，我相信我們已經為百時美施貴寶奠定了堅實的基礎。正如您將從我們的指導中註意到的那樣，我們預計今年的收入和非 GAAP 每股收益都會增長。重要的是，我們仍有望實現我們為 2025 年做出的承諾。鑑於對我們新產品組合的信心增強以及我們更廣泛的產品線不斷取得進展，我們看到了到 2030 年的多種增長途徑。

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。在幻燈片 5 上，您可以看到我們去年的整體管道執行情況。我對我們的進展感到非常滿意，這進一步支持了我們產品組合的更新。雖然我們在許多方面取得了進展，但我想強調一些成就。

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.

批准了 3 種一流藥物，包括 Opdualag、Camzyos 和 Sotyktu，它們解決了醫療需求未得到滿足的領域並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.

擴大我們新產品組合範圍的進一步進展，包括 Rebrozyl 在一線 MDS 和 COMMANDS 中的重要擴展機會，KarMMa-3 的積極收入增長，Abecma 是第一個證明其優越性的 BCMA CAR-T復發難治性多發性骨髓瘤的標準治療方案。並啟動 Sotyktu 在狼瘡中的註冊試驗。

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 II 期研究中，Sotyktu 在這種難以治療的疾病中表現出令人鼓舞的表現。我們相信狼瘡可以成為該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 在中風二級預防方面的重要概念驗證數據，使今年能夠啟動 III 期計劃以及我們的 LPA1資產在肺纖維化方面的積極試驗。

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.

該資產最近才受到關注，是擁有廣泛管道帶來的選擇性的一個典型例子。我們期待在今年晚些時候為該資產提供數據並開始 III 期試驗。

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.

在幻燈片 6 上，您可以看到我們如何加強新產品組合的前景，如您所知，這是我們在未來幾年更新產品組合的戰略的核心。

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.

我們的管道執行和強勁的商業勢頭使我們能夠在 2025 年實現 100 億至 130 億美元的風險調整後收入。由於我們管道的強勁進展，我們大大降低了 250 億美元以上的長期非風險- 風險調整後的收入潛力。正如您在這張幻燈片上還可以看到的那樣，我們繼續看到這些資產的激動人心的催化劑。

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.

因此，請轉到我們今年在幻燈片 7 上的記分卡。令人鼓舞的是，在短期內觀察到我們作為一家公司所看到的催化劑的廣度。我會指出幾個亮點。

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，我們宣布了 Breyanzi 在復發難治性 CLL 中的 I/II 期試驗達到了主要終點。在歐洲，我們希望在阻塞性 HCM 中推出 Camzyos，並且很高興收到 CHMP 對我們第一個也是唯一一個選擇性 TYK2 抑製劑 Sotyktu 的積極意見。我們的 ROS1 抑製劑 repotrectinib 有望在美國申請肺癌治療。

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.

我們在一線 MDS 中為 Rebrozyl 提供了一個重要的擴展機會。我們與我們在 Janssen 的合作夥伴一起，開始了 milvexian 的註冊試驗，我們希望將 Abecma 推向更早的治療線。

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我們的多發性骨髓瘤 CELMoD 計劃，在移植後維持環境中對伊比度胺與 Revlimid 進行面對面的研究。正如我們在前幾年所做的那樣，隨著我們繼續推進我們的管道並進一步支持我們的投資組合更新，我們期待著向您更新我們的進展。

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.

轉到幻燈片 8。我想提醒大家我們在過去幾年取得的成就，以及這些成就如何為我們的近期、中期和長期做好準備。 3 年前，當我們開始對公司進行轉型時，我們告訴過您我們相信我們可以實現的目標，並且我們已經全面交付。

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.

在財務上，我們發展了公司，實現了協同效應，減少了債務並產生了可觀的現金流。 9個新藥全部上市，包括去年獲批的首創產品3個。我們繼續執行有紀律的業務發展，以進一步支持我們未來的增長前景。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增長的能力的信心。

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，讓我轉到幻燈片 9 來討論我們今年及以後的展望。如您所知，隨著我們轉變投資組合，我們預計到 2025 年將推動增長並保持強勁的盈利能力。這一旅程今年仍在繼續。我們在 2022 年通過 Revlimid 仿製藥實現了增長。正如您從我們今天的指導中看到的那樣，我們預計今年將繼續增長。

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.

隨著焦點轉向本世紀下半葉，我們繼續看到多種增長途徑，這得益於新產品的增長、我們先進的後期管線（包括 Milvexian LPA1 和 CELMoD）的貢獻，以及我們的重要可選性早期管道，輔以額外業務開發的靈活性。一直以來，面對美國和國際上日益複雜的定價環境，我們正在轉變我們的投資組合，使其更年輕、更多元化、更有彈性。

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.

在我轉向大衛之前，讓我向我們全球的團隊表示感謝，首先是我們的研發組織，它在 2022 年表現出色。

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.

正如您所見，本週，我們宣布了 Rupert Vessey 博士退休的決定，該決定將於 7 月 3 日生效。我要感謝 Rupert 自收購 Celgene 後加入 BMS 以來所做的非凡貢獻。魯珀特領導了研究的成功整合，並在所有開發階段開發了強大的管道。

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.

我們現在正在 Samit 的領導下將早期和晚期的開發結合起來，並準備將研究組織轉變為向 Robert Plenge 博士報告，他將在 Rupert 今年夏天退休時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.

這些領導者和我們所有團隊的關注和解僱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?

我現在將其轉交給大衛，向您介紹財務狀況。大衛？

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 Giovanni，再次感謝大家今天加入我們的電話會議。我知道這對你們所有人來說都是一個忙碌的早晨。 .

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 Giovanni 所提到的，2022 年對 Bristol-Myers Squibb 來說又是一個堅實的執行年。讓我們從幻燈片 11 的最高業績開始吧。除非另有說明，否則所有比較都是與 2021 年同期進行的，銷售業績增長率將在基本基礎上進行討論，不包括外彙的影響。

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.

我們兌現了全年的承諾，銷售額約為 460 億美元，增長率為 3%。對我們多元化在線和新產品組合的需求強勁，全年收入增長 13%，足以抵消 Revlimid 在仿製藥上市第一年失去的獨占權。

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.

現在讓我更深入地了解幻燈片 12 上我們新產品組合的第四季度和全年業績。本季度全球收入為 6.45 億美元，增長 87%。雖然全年收入超過 20 億美元，比 2021 年幾乎翻了一番。隨著 9 項新產品的批准和多項其他適應症的取得成果，我們的新產品組合的風險越來越低。這使我們相信，我們有望在本十年末實現 250 億美元的非風險調整後收入，從而發揮我們新產品組合的潛力。

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.

轉到幻燈片 13，討論我們實體瘤產品組合的性能。全球 Opdivo 銷售額反映出對我們新推出的核心適應症的強勁需求，第四季度和全年均實現兩位數增長。在美國，第四季度全年銷售額增長強勁，分別增長 13% 和 15%。這種增長主要是由對我們新的轉移和輔助適應症的需求推動的，部分被二線資格下降以及 Opdualag 在一線黑色素瘤中的使用所抵消。

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.

在國際上，第四季度收入增長 20%，全年增長 14%。第四季度收入增長在很大程度上同樣受到需求和發貨時間的推動。需求主要受到新適應症的推動，尤其是上消化道癌症的一線肺癌。展望今年，我們預計 Opdivo 的增長將繼續。這種增長將來自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.

現在轉向我們的一流 LAG-3 抑製劑 Opdualag，它在上市第一年就表現出色，於 3 月下旬在美國獲得批准，Opdualag 在 2022 年實現了 2.52 億美元的銷售額。第四季度的銷售額強勁與第 3 季度相比連續增長 24%。由於一線黑色素瘤市場份額目前處於十幾歲，我們繼續看到 Opdualag 在一線黑色素瘤中的增長空間，其中 PD-1 單藥療法的份額仍約為 20%。以及正在進行的輔助黑色素瘤和二線加結直腸癌的關鍵研究的進一步潛力。

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，讓我們討論我們不斷增長的心血管產品組合，從 Eliquis 開始，它又是一個偉大的一年。第四季度和全年的全球收入分別增長了 6% 和 14%。在美國，第四季度銷售額增長 15%，主要受需求和有利的毛淨調整的推動。

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/地區的高市場份額，需求增長已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.

現在轉向我們一流的肌球蛋白抑製劑 Camzyos。第四季度的銷售額為 1600 萬美元。我們對自 2022 年 5 月推出以來取得的進展感到高興。我們為 REMS 認證的 2,600 多名醫療保健專業人員奠定了堅實的基礎，並使主要中心能夠做好運營準備，為患者提供 Camzyos。我們還顯著增加了使用商業配藥的患者數量，這為進入今年提供了強勁勢頭。我們期待繼續保持這一勢頭，並將 Camzyos 帶給歐洲患者，預計在年中獲得批准。

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，從 Revlimid 開始。受仿製藥進入的影響，全年全球銷售額約為 100 億美元。正如我們去年指出的那樣，我們預計季度之間存在差異。到 2022 年，我們看到仿製藥來那度胺在美國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.

鑑於 2022 年的受歡迎程度以及今年仿製藥銷量的預期增長，我們預計 Revlimid 的收入在 2023 年約為 65 億美元。我們繼續預計，作為 2024 年和 2025 年的合理假設，每年平均減少 25 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 全球收入在第四季度和全年繼續增長，這主要是由於對早期治療線中基於三聯方案的需求和延長患者治療時間的推動。與往常一樣，在第一季度，我想提醒您 Revlimid 和 Pomalyst 的典型季節性，因為患者在年初進入 Medicare 報廢。

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.

現在轉向我們一流的 EMA Rebrozyl。對 Rebrozyl 的需求強勁，第四季度和全年銷售額增長超過 30%。在美國，第四季度和全年的收入都增長了 20% 以上。自推出以來，我們通過提高患者依從性、延長治療持續時間和在 ESA 失敗時加速轉換取得了長足進步。

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， Rebrozyl 繼續在全球不同市場推出，目前在美國以外的 16 個市場推出。增長繼續受到 MDS 和 β 地中海貧血相關貧血需求的推動，並在更多國家獲得報銷。

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.

談到我們的差異化細胞療法產品組合 Abecma 和 Breyanzi，我們一流的 BCMA 細胞療法 Abecma 繼續保持強勁表現。全年全球收入為 3.88 億美元，而 2021 年為 1.64 億美元。這代表了強勁的同比增長，反映了患者的巨大需求以及公司為提高製造能力所做的工作。我們仍然專注於繼續提高產能，並相信這將使我們能夠將 Abecma 用於更多高度難治性骨髓瘤患者，並準備進入更早的治療線。

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，轉向我們一流的 CD19 細胞療法 Breyanzi。全年全球銷售額為 1.82 億美元，比 2021 年翻了一番多。本季度的銷售額反映了強勁的需求和我們團隊為擴大供應所做的努力。展望今年，我們繼續預計對 Breyanzi 和二線加大 B 細胞淋巴瘤的需求將推動增長，我們將繼續專注於繼續建設製造能力，以進一步支持吸收並為更多適應症做準備。

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 上我們擴展的免疫學產品組合，從我們一流的 S1P 激動劑 Zeposia 開始。受多發性硬化症和潰瘍性結腸炎需求增加的推動，第四季度銷售額增長了 69%，而全年全球銷售額幾乎翻了一番。我們擴大規模和改善商業准入的戰略正在實現。

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.

我們已經通過 0 步或 1 步編輯的幾個計劃取得了進展，隨著我們在 2023 年的推進，這將有意義地擴大訪問範圍。我們預計隨著時間的推移，Zeposia 的持續增長將主要從今天的 MS 發展到 UC。請記住，與進入第一季度的任何新免疫學藥物一樣，每年重置共同支付的典型動態往往會影響第一季度的表現，因為額外的共同支付支持——影響毛額對淨額的調整。在國際上，我們將繼續專注於在其他市場獲得報銷，以使 Zeposia 惠及更多 MS 和 UC 患者。

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，轉向我們用於中度至重度斑塊狀銀屑病的一流 TYK2 抑製劑 Sotyktu。到目前為止，我們對美國的發布感到非常滿意。仍處於早期階段，但醫生的反饋非常出色。截至 12 月，我們在 BRIDGE 和商業藥物方面擁有超過 2,000 個等效腳本。

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，我們繼續在新腳本方面取得進展，發現 Sotyktu 的使用大致平均分配給系統性初始患者、Otezla 轉換患者和生物轉換患者。我們仍然專注於推動對這種新藥作為口服選擇的需求，並確保盡可能多的患者在 2024 年獲得 Sotyktu 以實現更廣泛的處方地位。在國際上，我們現在在日本和加拿大獲得批准，預計在年中獲得歐洲批准。

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.

在幻燈片 17 上切換到我們的第四季度損益表。剛剛介紹了銷售業績，讓我帶您了解一些非 GAAP 關鍵項目。正如預期的那樣，第四季度毛利率主要受到產品組合和更高製造成本的影響。全年毛利率約為 79%，符合我們先前的指引。不包括收購的在製品研發，第四季度和全年運營費用下降的主要原因是我們增長機會背後的投資重新分配，以及外彙和轉折點收購稀釋的影響。

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%.

本季度獲得的在製品研發費用為 5200 萬美元，部分被本季度有利於 OI&E 的 1600 萬美元許可收入所抵消。第四季度有效稅率約為 11%，受收益組合和一次性項目的推動，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，第四季度每股收益為 1.82 美元。從全年的角度來看，我們以 7.70 美元的價格在我們的指導範圍的上限結束了這一年，比上一年增長了 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.

轉到幻燈片 18 的資產負債表和資本配置。第四季度的運營現金流為 33 億美元。截至 12 月 31 日，該公司的資產負債表依然強勁，手頭現金和有價證券約為 90 億美元。

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.

我們的資本配置優先順序沒有改變。業務發展仍然是進一步更新和多元化我們的投資組合併加強我們的增長前景的重中之重，同時還關注資產負債表的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開發交易，並於去年收購了 Turning Point Therapeutics。我們強大的資產負債表使我們能夠不受交易規模的影響。由於這與 2022 年的資產負債表實力有關，我們減少了超過 50 億美元的債務，並且我們致力於維持強大的投資級信用評級。

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，由於涉及向股東返還資本，我們擁有連續 91 年支付股息的長期記錄，最近連續第 14 年增加股息。我們仍然致力於增加股息，但須經董事會批准，並繼續在股票回購方面採取機會主義態度，我們的股票回購授權剩餘約 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.

讓我以我們在幻燈片 19 上的 2023 年非公認會計準則指導作為結尾。由於不可預測的宏觀經濟因素和去年外彙的大幅波動，我們在報告基礎和基礎基礎上提供指導，假設貨幣與之前的匯率保持一致年。

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 年收入按報告和固定匯率計算將增長約 2%。這反映出我們有信心，我們的在線和新產品組合將足以抵消 Revlimid 和 Abraxane 的 LOE 影響。我們預計 Revlimid 銷售額約為 65 億美元，假設在第一季度晚些時候向仿製藥製造商進一步升級，以及季度與季度之間的持續變化。

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.

憑藉我們新產品組合的發展勢頭，我們預計它比去年增長一倍左右，約為 40 億美元。由於它與我們今年的項目指導相關，我們預計我們的毛利率約為 77%，這反映了產品組合的轉變。我們不預測收購過程中的研發。

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，排除這一點，我們預計我們的總運營費用將下降到較低的個位數範圍內。這反映了隨著我們繼續投資新產品，MS&A 中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.

由於我們動態的研究組合宣讀和新研究的啟動，預計研發費用將與去年基本持平。我們預計我們的稅率約為 17%，反映了波多黎各稅法和產品組合的變化。

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，我們預計我們的非 GAAP 每股收益將增長至 7.95 美元至 8.25 美元。這代表了大約 5% 的增長。不包括上一年收購的在建研發，調整後的每股收益將增長約 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，我要感謝我們世界各地的同事在 2022 年的強勁表現。我們在 2022 年的強大執行力和我們對 2023 年的承諾反映了我們業務的彈性和我們產品組合的更新。今年的業績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 questions and answers.

我現在將把電話轉回給 Tim 和 Giovanni 來提問和回答。

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。我知道今天很忙。所以我們要進入問答環節。如果您可以只問一個問題，那將非常有幫助。丹尼斯，我們可以轉到第一個問題嗎？

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。它來自美國銀行的 Geoff Meacham 系列。

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。我會把它留給一個。所以，Sotyktu，我意識到現在還處於發布初期。但是，隨著你們市場份額的提高，今年有哪些改善處方定位的機會？今年推出的許多生物仿製藥， Humira 以及 - 全面對這些 PBM 討論中的任何一個產生影響嗎？

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。謝謝你的問題，傑夫。這是克里斯。我要買它。首先，我們對 Sotyktu 的表現非常滿意。現在顯然還處於早期階段，但正如 David 剛才的評論所反映的那樣，該產品的反響非常非常好。我們從客戶那裡得到的關於配置文件的反饋是好的。

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，我們現在擁有 2,000 多個腳本，我們在中度至重度牛皮癬口服市場的新產品市場份額約為 35%。如果你看一下整個市場，它大約是 12%，那是在發布 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.

非常高興我們看到第四季度的勢頭。由於它與我們是否可以加速訪問位置有關，我認為我們描述它的方式是基本情況仍然是 2024 年，以便進入更好的訪問位置。也就是說，我們正在竭盡所能加速這一進程。我們顯然正在與付款人進行良好的討論。我們擁有的潛在加速策略保持不變，即繼續盡快推動對該產品的需求。好消息是我們有資料，我們看到了客戶的反饋，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.

至於生物仿製藥的影響，顯然，這是一個動態的環境。在過去的幾周里，你已經看到了一些動作。我要說的是，我們獲得准入的方法實際上並沒有根據我們對生物仿製藥的了解而發展。我們認為 2023 年將是生物仿製藥的過渡年。顯然，公司和 PBM 的戰略將繼續發展。所以這是我們將保持領先地位的事情。但正如我們現在所說，當然，我們對 Sotyktu 的戰略不會改變。

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?

有了 Camzyos，推出它的進展，你之前已經談到了卓越中心的不同組合，你給了我們一個病人號碼。您能否告訴我們這些較大的中心與較小的實踐的相對分佈是什麼？您是否看到了認證設置的勢頭以及您目前希望的患者流量？

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有很好的加速。正如我想大衛提到的那樣，我們現在有超過 1,800 名患者已經開過處方。重要的是，我們看到這些腳本向商業藥物的轉化良好且不斷增加。您可能還記得，在第三季度，我們談到了 30% 的腳本轉換為商業藥物。在第四季度，這一比例為 50%。所以我們在那裡獲得動力。

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反饋仍然非常強烈。所以我們看到了一個不錯的皮卡。我要說的是，這種回昇在第四季度加速了。回想一下，我們的目標是全國大約 500 個帳戶。這些佔患者總數的大約 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的是在這些賬戶中使用 Camzyos 的速度非常快。重要的是，我們一直關注的一些較慢的賬戶繼續建立必要的基礎設施，讓患者接受治療。因此，我們也看到了這些特定帳戶的良好加速。所以總的來說，我們覺得我們在 2022 年結束時取得了良好的進展。

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?

剛回到Sotyktu。當您考慮競爭一線市場份額時，輕度至中度 Otezla 標籤是否代表了 Sotyktu 的障礙？顯然，你們現在看到了一些，但你們認為這是一個障礙嗎？

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?

也許我會很快地插入第二個。Eliquis，你在 2022 年的大部分季度都看到了有利的毛淨比。這會在 23 年繼續嗎？或者我們應該考慮今年的增長，也許更符合銷量增長？

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。這兩個我都要。謝謝你的問題，克里斯。關於 Sotyktu，我們認為 Otezla 更廣泛的市場進入溫和類別不會對我們產生影響。事實上，我們看到的是 Sotyktu 在中度至重度患者中的強勁勢頭。當我們與客戶交談時，我們從他們那裡聽到的是，我們很高興在我們標籤的所有範圍內使用該產品，其中不僅包括重症患者，而且重要的是，還包括那些中度患者。

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.

然後，如果你看看我們目前看到的吸收情況，它反映了一個事實，即醫生願意使用它，實際上無論是中度還是重度。因此，鑑於我們有 2 項 III 期研究清楚地顯示了相對於 Otezla 在患者人群中的優勢，我們認為這不會成為我們考慮產品吸收的特殊障礙。

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 的毛淨值，如您所知，到 2022 年，我們確實看到了一些有利因素，主要是由於業務來源和渠道組合。但眾所周知，這個領域是一個競爭非常激烈的領域。它的管理很嚴格。所以我們沒有看到我們期待的毛對淨的好感度。各季度將繼續存在差異。正如我們過去多次談到的那樣，您確實會看到像 Eliquis 和 gross-to-net 這樣的產品的年末季節性。但從前瞻性的角度來看，我們看不到該產品對淨利潤的青睞。

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

下一個問題來自古根海姆的 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 和可能在今年年底被選中進行談判的藥物。只是想知道布里斯托爾將如何特別處理這種情況？

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.

我知道你們確實有專利到期會限制那裡的影響。但如果從 2026 年開始，考慮到 Bristol 目前的產品組合，Eliquis 是那裡的頂級玩家之一。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?

我們看到了至少運行了整整一年的免費藥物發布，可能不是純粹的免費藥物，而是大量的幫助。試圖更好地理解，特別是對於口語，它開始看起來像那裡的生命週期開始被縮短到 6 到 7 年。想知道您是否對 IRA 內部的口服激勵與生物激勵更好地結合感到舒服甚至有信心？

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，西默斯。這是喬瓦尼。我來回答這個問題，我會請 Chris 對你關於免費商品策略的第二個問題發表評論。所以我認為當你看 IRA 時，類似於我們之前的討論，我會說有很多我們仍然不知道。

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 正在研究實施立法的程序方面，當然，在今年的過程中，我們會學到更多。現在，當您查看有關 BMS 的問題時。因此，首先，我們知道，直到 2026 年一些政府定價開始時，我們才會看到 IRA 的影響。你是對的，Eliquis 有可能在 2026 年受到影響。因此，當然，我們需要了解更多信息才能了解影響的程度。我只是提醒你，雖然我們為 Eliquis 預訂了 100% 的收入，但顯然，我們與輝瑞公司分享了利潤。因此，在許多方面，它是一個重要的品牌，但就確定我們的收益軌跡與您對收入線的看法而言，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通過 IRA 的執行和實施來繼續發展公司。在許多方面，我們正在做的正是將新藥推向市場，以加速我們產品組合的更新。因此，當您展望 2026 年時，我們預計新發布品牌的銷售額將達到 100 億至 130 億美元。我會說將會有一個非常有活力的年輕投資組合，這將推動公司下半年的增長。當然，這些產品將在最近推出，因此暫時不會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，我要發表的最後一條評論是，您所指的與本土差異相關的挑戰是正確的，口服 9 年，生物製劑 13 年。我們顯然對此並不滿意，因為科學正在使我們能夠交付——開發越來越多的分子。但顯然，那裡的任何變化都需要修改立法。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。 Seamus，這是一個關於免費藥物計劃在 IRA 方面發揮的作用的有趣問題。我想你們大多數人都知道，免費藥物計劃是典型的，特別是在回扣要求您有一個過渡期的市場中，特別是對於新產品進入更有利的准入位置。

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.

現在有一種動態，因為這些免費藥物計劃通常針對商業付款人。我的意思是，商業病人和 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，在某種程度上，免費藥物和免費藥物計劃會長期發揮作用，當你看到 IRA 限制和價格設定時，它可能會產生負面影響, 在 9 年。

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加強的是非常強大的商業執行的重要性，因為很明顯，你想要做的是盡快從免費藥物過渡到更有利的獲取位置。正如我們剛剛討論的那樣，對於像 Sotyktu 這樣的產品，這將繼續成為我們的重點。但我認為這是一個非常重要的問題。隨著我們更多地了解 IRA 的推出，我們將不得不繼續監控這一點。

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

下一個問題來自 Steve Scala 與 Cowen 的對話。

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，Bristol 啟動了 milvexian SSP III 期試驗，並於 2026 年 11 月初步完成，另外的 III 期試驗將在今年上半年開始。但拜耳的研究預計將提前一整年宣讀。這與您認為布里斯托爾落後拜耳一年的看法一致嗎？我應該補充一點，你不是第一個使用 Eliquis 並最終佔據主導地位的人，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.

薩米特在這裡。看，我們計劃了這些研究，並根據入學情況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，然後才能宣讀和報告結果。所以我們必須考慮所有這些因素，當然，我們可以通過查看註冊率以及這些試驗的註冊方式來影響臨床試驗。

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.

所以我認為你在 ClinicalTrials.gov 上看到的是我們對試驗何時結束的猜測。通過我們可能會更早地閱讀。我們的競爭對手可能會在稍後閱讀。但現在還處於早期階段，如果時間線確實發生變化，我們會隨著試驗的進展向您更新。

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。您能否根據覆蓋的生命數量量化 22 年市場准入的位置？在您有權訪問的地方，是否有任何步驟首先需要 Otezla？然後在您的 BRIDGE 計劃中，它會一直持續到 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，關於市場准入，我們認為我們有大約 10% 的患者參與了開放或優先准入的計劃。顯然，隨著我們繼續與付款人接觸，這一數字將繼續增加。正如我們所說，我們在主要 PBM 中獲得更有利的訪問位置的基本情況是 2024 年，但我們正在盡一切努力加快這一進程。

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 程序，BRIDGE 程序在這個市場中很典型，我認為我們通常會考慮保持這些 BRIDGE 程序的開放，直到我們發現我們有能力協商更快的訪問或與大型 PBM 的接觸更有利。

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.

蒂姆，我們在 Sotyktu 看到的一件好事是，絕大多數患者都進入了我們的中心。這使我們能夠做的是監測這些患者在處方定位方面的狀況。因此，即使該 BRIDGE 計劃是開放的，我們也有能力將這些患者轉變為商業藥物，只要我們證明他們的計劃能夠讓他們服用商業藥物。

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，這是一個比我們所進行的討論中所表明的更具活力的過程。事實上，我們有能力更實時地看待這個問題。但我們確實預計，隨著我們進入 2024 年，這些 BRIDGE 計劃肯定會繼續開放。

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

下一個問題來自 BMO 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?

在 Abecma 上，你從 2022 年初努力滿足患者需求到現在擴展到更早的治療線。現在我們應該如何考慮彌合這一差距，我真的在談論擴大產能，以及何時我們可能會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，也許我會拿那個。這是克里斯。因此，我們實際上對 Abecma 繼續看到的產能擴張感到非常滿意，實際上，我們在第四季度看到了這兩種產品。您可能還記得，對於 Breyanzi，我們曾預計產能擴張會等到今年。我們很高興看到擴張加速到第四季度。

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.

所以我認為，正如我們對今年的期待，我們將繼續看到細胞產品、細胞治療產品的產能擴張，這對 Abecma 來說確實如此。我想說的另一件事是我們考慮了製造，這將繼續成為我們細胞治療的重點領域，因為我們有一個三重戰略。

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。坦率地說，這是影響所有細胞治療產品的更重要因素之一。這些是複雜的藥物，它們是活的產品，你必須專注於你的製造成功率。

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矢量供應，我們顯然有許多策略在發揮作用，從雙重採購到增加套件數量，並最終在這方面轉向下一代懸掛矢量。

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。在那裡，它主要是關於使更多的製造站點在線，我們之前已經討論過我們在馬薩諸塞州德文斯的努力，開明了這樣做。所以我想說的是，製造業必須繼續成為我們關注的一個領域。我們已經制定了良好的戰略，而且我們已經看到這些戰略隨著產能的擴大而發揮作用，不僅在第四季度，而且我們預計將在今年剩餘時間內實現。

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

下一個問題來自特倫斯弗林與摩根士丹利的對話。

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，可能適合你。僅考慮指導，OpEx，今年你指導了較低的個位數下降，這抵消了一些毛利率壓力。而研發，你持平。因此，看起來大部分下降將出現在 SG&A 方面。因此，正如我們展望 2024 年一樣，我想我們預計，鑑於 Revlimid 的全面推出，我們將面臨額外的毛利率壓力。當我們考慮進入 24 世紀的節奏時，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。你是對的，因為它與毛利率有關，我們確實預計它們會下降。去年與預期一致，因為我們今年的指導是 77%，因為收入下降時產品組合。

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.

就運營支出而言，我們繼續尋找效率和運營效率。我們通過 COVID 和數字技術學到了很多東西，特別是關於我們如何與醫療保健專業人員打交道。但最重要的是，將成熟品牌的資源重新分配給我們推出的產品，確保它們得到充分的資助，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，當我們談到研發支出水平時，它實際上是由我們的投資組合驅動的。這對研發支出水平的影響最大，我們剛剛推出了 9 種新產品。所以我們有很多後期項目下線了。我們有一些新的上線，但其中一些是通過合作夥伴關係。我認為 milvexian 是一個很好的例子，我們有幾個即將開始的 III 期項目，但與我們共享——這些成本與我們的合作夥伴共享。

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，這就是為什麼我們相信，當我們審視今年的業務時，我們預計整體運營費用將出現低個位數的下降。但即使毛利率下降，我們也非常有信心。當我們審視我們的基礎時，繼續以比我們的費用基礎更快的速度增長收入，這使我們能夠靈活地將這些營業利潤率維持在 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點。所以從我們的數學來看，對於在線產品來說，你正在尋找另一個非常好的年份。因此，在增長了 11% 之後，我們計算得出，您預計今年將再次增長 8%，這似乎是您與共識之間的差值。那麼，您能否談談那裡的 puts 和 takes？考慮到 Eliquis OUS 的挑戰，您認為在線產品組合中哪裡增長最強勁？

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，謝謝你的問題。你是對的。我們確實看到了我們在 23 年增長的多個驅動因素。正如我所說，總體而言，我們的在線和新產品組合增長了 2%，抵消了我們在 Revlimid 和 LOE 中的下降。當我們考慮在線時，這確實發生了。正如我們之前談到的，過去一年我們在 Eliquis 上取得了非常強勁的兩位數增長。儘管我們在歐洲看到了一些不利因素，但我們繼續看到增長，美國和 Opdivo、Yervoy 的良好強勁增長以及我們額外的腫瘤適應症和輔助設置。我們繼續看到肺癌和胃癌的良好增長，並繼續看到我們的 IO 特許經營繼續保持非常強勁的增長。

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，這是一個重要的增長動力。正如我在之前的發言中所說，去年這一數字翻了一番。正如我們所說，我們看到這種情況會持續到今年。因此，在在線業務以及我們去年退出時所擁有的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增長，我們對自己的能力非常有信心今年這樣做。

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

你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?

也許您在這里關注 Rebrozyl 的其中一個發布產品。你提到了一些持續時間的增長。會喜歡您可以在那裡提供的任何其他顏色嗎？然後，當您考慮 COMMANDS 時，我們應該如何考慮第 8 階段的歸檔以及我們何時可以看到該數據？這是我們可能需要等到 6 月 4 日晚些時候的事情嗎？或者是否有機會在此之前共享該數據？

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。也許我會先開始，然後將它切換到 Samit 以回答您關於 COMMANDS 的問題。因此，關於 Rebrozyl，是的，我們繼續看到 Rebrozyl 的新患者從第四季度開始獲得良好的收購。當然，我們希望看到這種情況會持續到今年。

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.

但正如您所注意到的，我們看到該產品最顯著增長的潛力實際上是——首先是增加劑量和給藥，並確保我們對患者進行正確的滴定。去年，我們在這方面看到了一些改進。

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，與 2021 年相比，2022 年的治療持續時間增加了 6%，我們預計會繼續看到，特別是隨著患者隨著時間的推移逐漸增加，這與 MEDALIST 研究一致，即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.

然後我們關注的第二大領域是讓那些在一線環境中不再對 ESAs 做出反應的患者轉向 Rebrozyl。這對我們來說是一個很大的關注領域。

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.

再一次，在這裡，兩個，我們取得了很好的進展。自我們批准以來，ESA 的時間從大約 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 年關注的兩大方面。很明顯，COMMANDS 研究為增長提供了下一個重要催化劑。我們認為，這表明我們將大約有兩倍於 Rebrozyl 的機會。但就時間而言，我認為 Samit 可以說明這一點。

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，也謝謝卡特提出的問題。所以我們現在沒有我們會議的具體細節，我們可以在那里共享數據。但當然，我們會在信息可用時確認這一點。

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.

在提交文件方面，我們不會對此發表評論，直到我們 - 我們發布 - 我們在文件被接受後發布新聞稿。但肯定對數據感到滿意，正如 Chris 剛才提到的那樣，COMMANDS 是一項重要的研究，用於將我們的 Rebrozyl 移至前線，我們將其與 ESA 的主動控制進行比較並顯示出優勢。

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

下一個問題來自馬特菲普斯和威廉布萊爾。

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?

您在幻燈片中指出，決定不將 Cendakimab 推進特應性皮膚。這是第二階段產品概況中的特定內容嗎？還是可以通讀正在進行的 EoE 試驗？或者它只是特應性皮炎的競爭動力？

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。看，記住，我們一直說，在推進我們的計劃時，我們總是查看數據，我們希望看到這些數據的差異，然後，當然，還要查看景觀和競爭動態。對於特應性皮炎，最近有幾種療法可供患者使用，它們非常有效。因此，在為特應性皮炎患者帶來差異方面，我們將門檻設定得相當高。

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可供患者使用的產品相比沒有競爭優勢。因此，我們不會進入註冊試驗階段。但這與我們在嗜酸性粒細胞性食管炎中看到的 cendakimab 無關，在那裡我們不僅看到了嗜酸性粒細胞浸潤的變化，而且還看到了患者吞嚥困難和 Phase 纖維化結果的動態變化二、學習。為了讓研究繼續進行，當然，我們將在研究完成後分享結果。

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

你的下一個問題來自 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。感謝你的提問。所以你在狼瘡中有 TYK2，在狼瘡中有 Sotyktu。今年晚些時候，輝瑞和 JAK 加上 TYK2 將進行 III 期試驗。如果該試驗失敗，也許可以將其框定下來，例如您對生物學有何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.

然後是食物問題，如果它成功了，我們如何從生物學的角度思考，如果你知道在 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，但是您能給我們提供任何有關功效的信息，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。感謝你的提問。如果您考慮一下，今天還沒有 JAK 抑製劑獲批用於治療銀屑病患者。我們證明了 TYK2 抑製劑的好處，它對 IL-12、IL-23 和乾擾素具有非常特殊的下游作用，這當然很重要。在過去一年或什至更長的時間裡，我們一直在回答差異化問題，並從安全角度保護 TYK2 抑製劑與 JAK 抑製劑的概況。

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，如果您現在快進並考慮一下，對於我們剛剛顯示出優於口腔環境中使用的先前護理標準的患者群體，我們已經進行了 2 項試驗優勢。我們已經獲得了銀屑病關節炎和系統性紅斑狼瘡的 II 期數據，並且我們正在進行所有這些適應症的 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.

因此，我認為 Sotyktu 的形象現在已經很好，我認為，我們對數據和數據演變的信心使醫生很有希望開出它，正如克里斯之前談到的那樣。所以我們將依靠這些信息和我們自己的分子數據的演變。

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.

當他們的數據被讀出時，我不能說輝瑞會做什麼。但可以肯定的是，我敢肯定你們都會問這個問題，當這些患者可以使用有效的安全療法時，JAK 抑製劑對銀屑病的治療是否正確。

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

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

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，也許一個給你。今年以後的 Revlimid 銷售預期是否有任何更新？我知道你過去曾談到每年減少 20 億美元以上。但是你對那裡的收入運行率的想法有什麼變化嗎？然後是關於 Sotyktu 的快速澄清問題。你們在哪裡進行高劑量計劃？我們能否看到它在某個時候進入 UC 以外的任何適應症？

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。奧利維亞，我是大衛·埃爾金斯。我會服用 Revlimid 的。我們對 Revlimid 到 2025 年的展望沒有真正改變。我們提供了今年的最新情況，即 65 億美元，鑑於去年 2022 年的更好表現，這減少了 35 億美元。當我們考慮“24 和” 25，平均而言，大約 25 億美元的降級是我們的想法。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.

實際上，謝謝你，大衛。所以 Olivia，當然，所以 TYK2 有 2 項正在進行的 IBD 研究。其中之一在潰瘍性結腸炎中使用了更高的劑量。如果您還記得的話，我們目前還沒有潰瘍性結腸炎或 IBD 的概念驗證。而且 - 我們想要測試的假設之一是在 IBD 中或特別是在潰瘍性結腸炎中使用更高劑量的 Sotyktu。

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.

所以我們很期待看到今年下半年的數據。並根據依賴於結果的數據，然後我們將能夠制定關於如何在 IBD 和/或其他適應症中以更高劑量推進的策略。

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，我們還在之前的試驗和其他適應症中測試了更高的劑量，並且我們的安全性特徵在這些臨床試驗中得到了保持。因此，我們不一定期待在更高劑量下可能出現的任何主要信號，但肯定會尋找療效信號。

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

我們的下一個問題來自花旗銀行的 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 拮抗劑的幾個問題。你能提醒我們什麼時候可以看到第二階段的數據嗎？而且，鑑於羅氏 Pentraxin 今天的失敗，您如何看待 III 期試驗設計？最後，除了 IPF 之外，您正在尋找該藥物的纖維化適應症是什麼？

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。所以 LTA1 當然，我們期待在今年上半年內提供數據。當然，一旦我們對會議進行了確認，我們將能夠分享該信息。

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，因為你指的是羅氏，III 期試驗已經停止。我們確實看到我們的數據，我們迄今為止看到的第二階段數據非常強大。我們已經討論了沒有背景護理標準的患者群體以及與護理治療背景標準相結合的患者群體，我們對所看到的情況感到滿意。我們正在與監管機構討論臨床試驗設計的適當性，你會在我們啟動和公開時看到這一點。因此，將在適當的時候進行更多跟進。但真的很高興。

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.

最後一個關於額外纖維化項目的問題，我們現在從兩個角度來看 LPA1。一個是 IPF 計劃，另一個是進行性肺纖維化。但第二階段的數據將在今年晚些時候公佈。所以我們現在正在研究這兩件事。

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

今天的最後一個問題將來自 Colin Bristow 與 UBS 的對話。

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。我看到你有另一種 TYK2 抑製劑處於 I 期。你能給我們任何顏色嗎？你如何預期它與 TYK2 的區別？然後是 287 上的另一個問題，您最近終止了非小型基站的第一階段開發。這是我們的反TIGIT之一。我認為你提到了安全問題。我只是想知道你是否可以具體說明這些問題是什麼。

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。關於您關於下一個 TYK2 抑製劑正在進行的 I 期的第一個問題。總的來說，我們總是有 1 或 2 個項目在開發下一代分子方面進行研究。所以這只是我們有額外的 TYK2 抑製劑的通用管道開發的一個階段。我們還有一種處於 I 期的 CNS 滲透劑 TYK2 抑製劑。所以現在沒有什麼特別要談的。但可以肯定的是，隨著數據的出現，隨著數據的發展，我們將來將能夠共享這些數據。

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，旨在觀察納武單抗和易普利姆瑪的聯合用藥。到目前為止我們所看到的，我不會詳細說明，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，對於這種特定的 TIGIT 抑製劑，當與雙 I-O 療法聯合使用時會觀察到毒性.

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.

因此，隨著我們獲得更多見解和更多細節，將會有更多數據出現，然後將完成演示。但出於這些安全原因，我們決定此時終止此特定試驗。

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 Samit，也感謝大家的參與。正如您所見，這對公司來說是一個激動人心的時刻。我們又迎來了重要的一年，有很多事情要談。但我們知道，對於你們所有人來說，這是一個非常忙碌的早晨。所以我們要在這裡結束通話。與往常一樣，如果您有任何其他問題，請聯繫我們的團隊。所以謝謝大家，祝你有美好的一天。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.

這確實結束了 Bristol-Myers Squibb 的 2022 年第四季度收益電話會議。感謝您的參與。您現在可以斷開連接。