施貴寶 (BMY) 2023 Q4 法說會逐字稿

Welcome to the Bristol-Myers Squibb Fourth Quarter 2023 Earnings Conference Call. (Operator Instructions) Please note, this event is being recorded. I would now like to turn the conference over to Tim Power, Vice President and Head of Investor Relations. Please go ahead.

歡迎參加百時美施貴寶 2023 年第四季財報電話會議。 （操作員說明）請注意，正在記錄此事件。現在我想將會議交給副總裁兼投資者關係主管 Tim Power。請繼續。

Thank you, and good morning, everyone. Thanks for joining us this morning for our fourth quarter 2023 earnings call. Joining me this morning with prepared remarks are Chris Boerner, our Chief Executive Officer; and David Elkins, our Chief Financial Officer. Also participating in today's call are Adam Lenkowsky, our Chief Commercialization Officer; and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development. As you'll note, we've posted slides to bms.com that you can use to follow along with for Chris and David's remarks.

謝謝大家，大家早安。感謝您今天早上參加我們的 2023 年第四季財報電話會議。今天早上與我一起發表準備好的演講的是我們的執行長 Chris Boerner；和我們的財務長大衛埃爾金斯。參加今天電話會議的還有我們的首席商業化長 Adam Lenkowsky；以及我們的首席醫療官兼全球藥物開發主管 Samit Hirawat。您將注意到，我們已將幻燈片發佈到 bms.com，您可以使用這些幻燈片來了解 Chris 和 David 的演講。

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

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

We'll also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items. Reconciliations of 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 GAAP 指標的調整表可在 bms.com 上找到。

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

有了這個，我會把它交給克里斯。

Thanks, Tim, and good morning to all of you. I'm very pleased to be speaking to you on our earnings call for the first time as CEO, and I'm excited about the opportunity for our company to continue to deliver transformational medicines for patients. Please turn to Slide 4.

謝謝蒂姆，祝大家早安。我很高興第一次以執行長的身份在我們的財報電話會議上與您交談，我對我們公司有機會繼續為患者提供變革性藥物感到興奮。請翻到幻燈片 4。

Q4 2023 was a good quarter, including strong sales momentum in our in-line and new product portfolio with 9% growth and nearly $10 billion in revenue with growth across multiple key brands, including Eliquis, Opdivo, Reblozyl, Opdualag, Breyanzi, Camzyos and Sotyktu. We also continued to generate significant cash flows from operations of $4.3 billion in the quarter. And as you'll hear from David in a few minutes, we expect to grow our business this year.

2023 年第四季是個不錯的季度，包括我們的內嵌產品和新產品組合的強勁銷售勢頭，成長9%，營收近100 億美元，多個主要品牌均實現成長，包括Eliquis、Opdivo、Reblozyl 、Opdualag、Breyanzi、Camzyos 和索提克圖。本季我們也繼續從營運中產生 43 億美元的大量現金流。幾分鐘後您就會聽到 David 的來信，我們預計今年的業務將會成長。

During the fourth quarter, we also achieved important pipeline milestones in several key business development transactions to strengthen our growth profile. This is an important time for BMS. I know that many of you are focused on our strategy to navigate the decade and on the importance of disciplined execution at the company. We are writing the next chapter for BMS and with that, comes an opportunity for change. So let me take a few minutes to tell you about our strategy to navigate our LOEs and be very clear about my focus on execution.

在第四季度，我們還在幾項關鍵業務發展交易中實現了重要的管道里程碑，以增強我們的成長前景。對 BMS 來說，這是一個重要的時刻。我知道你們中的許多人都關注我們這十年的策略以及公司嚴格執行的重要性。我們正在為 BMS 譜寫新篇章，隨之而來的是改變的機會。因此，讓我花幾分鐘向您介紹我們的 LOE 策略，並明確我對執行的關注。

Let's go to Slide 5 and how we see the company today. When we look at our business, it's comprised of 2 portfolios. First, we see a legacy portfolio of well-established products fading headwinds such as IRA. Though this portfolio is declining, it is expected to continue to generate strong cash flows to enable investment in our future growth drivers.

讓我們看投影片 5，看看我們今天如何看待這家公司。當我們審視我們的業務時，它由兩個投資組合組成。首先，我們看到 IRA 等成熟產品的傳統投資組合正在消退。儘管該投資組合正在下降，但預計將繼續產生強勁的現金流，以支持對我們未來成長動力的投資。

Second, we see an expanding portfolio of growth products, many of which are relatively newer to the market and have significant expansion potential. When you look at these portfolios, combined with our exciting pipeline, you can see how it all comes together as depicted on Slide 6. As we think about this decade, we see 3 distinct periods: a near-term growth period, a transition period and potential for sustainable top-tier growth, which we plan to drive in the back end of the decade.

其次，我們看到成長型產品組合不斷擴大，其中許多產品相對較新，具有巨大的擴張潛力。當您查看這些投資組合以及我們令人興奮的管道時，您可以看到它們是如何組合在一起的，如幻燈片6 所示。當我們思考這十年時，我們看到3 個不同的時期：近期成長期、過渡期以及永續頂級成長的潛力，我們計劃在本世紀末推動這一成長。

Between now and the middle of the decade, our focus will be on maximizing the opportunity we have with our growth portfolio. This, along with pipeline execution, can best position the company into the transition period. Then starting around 2026, our exposure is most acute, and our focus will be on shortening the transition period as much as possible by accelerating our R&D programs, executing on product approvals and launches while maintaining P&L discipline.

從現在到本世紀中期，我們的重點將是最大限度地利用我們的成長投資組合所擁有的機會。這與管道執行一起可以使公司最好地進入過渡期。然後從 2026 年左右開始，我們面臨的風險最為嚴重，我們的重點將是透過加快研發計劃、執行產品審批和發布，同時保持損益紀律來盡可能縮短過渡期。

Finally, in the latter part of the decade, around 2028 and beyond, we plan to deliver sustainable top-tier growth, and we have the portfolio, pipeline and financial flexibility to support this opportunity. Many of you recognize the first 2 periods. However, the late decade return to growth phase is less appreciated externally, including a number of important products that are not fully appreciated in consensus models today. What supports our confidence is our expanding pipeline, recent deals and newly launched products. Our strategy is to minimize the transition period coming in a few years while maximizing our growth in the back part of the decade.

最後，在這個十年的後半段，即 2028 年左右及以後，我們計劃實現可持續的頂級增長，並且我們擁有投資組合、管道和財務靈活性來支持這一機會。你們中的許多人都認識前兩個時期。然而，十年後恢復成長階段的外部評價較少，包括許多重要產品在當今共識模型中尚未充分評估。支持我們信心的是我們不斷擴大的產品線、最近的交易和新推出的產品。我們的策略是最大限度地縮短未來幾年的過渡期，同時最大限度地提高我們在十年後的成長。

Turning to Slide 7. My confidence in our strategy is supported by the fact that compared with other companies that successfully navigate at similar periods, we have some clear strengths, an expanding growth portfolio across multiple therapeutic areas, an exciting pipeline, differentiated platforms and continued financial strength to further invest for growth with business development.

轉向幻燈片7。我對我們​​策略的信心得到了以下事實的支持：與在同一時期成功發展的其他公司相比，我們擁有一些明顯的優勢、跨多個治療領域的不斷擴大的增長組合、令人興奮的產品線、差異化的平台和持續的發展。財務實力可進一步投資以促進業務發展。

And the momentum from our most recent quarter to capitalize on these strengths is clear from Slide 8. In October, we told you we would strengthen commercial performance. And during Q4, we've been making progress. We have increased investment behind key growth brands such as Camzyos and Sotyktu. We are reaccelerating growth for Reblozyl by capitalizing on the launch of the COMMANDS indication first-line MDS. Our efforts to further establish Opdualag as the standard of care in first-line melanoma are driving further growth.

從投影片 8 可以清楚地看出我們最近一個季度利用這些優勢的勢頭。10 月份，我們告訴您我們將加強商業業績。在第四季度，我們一直在取得進展。我們增加了對 Camzyos 和 Sotyktu 等關鍵成長品牌的投資。我們利用 COMMANDS 適應症第一線 MDS 的推出，重新加速 Reblozyl 的成長。我們進一步將 Opdualag 確立為一線黑色素瘤治療標準的努力正在推動進一步的成長。

And we have made progress expanding capacity for cell therapies, particularly setting up Breyanzi for significant expansion this year. In R&D, we delivered important milestones, including recharging our early-stage pipeline with 10 INDs as we told you we would do at our R&D Day, delivering the approval of Augtyro in first-line ROS-positive lung cancer, and advancing our key platforms, including initiating our CD19 NEX-T study in multiple sclerosis for our cell therapy program, and showing early but important Phase I data for the AR-LDD prostate [assay] from our targeted protein degradation platform.

我們在擴大細胞療法產能方面取得了進展，特別是今年設立了 Breyanzi 進行大幅擴張。在研發方面，我們實現了重要的里程碑，包括用 10 個 IND 為我們的早期管道充電，正如我們在研發日告訴您的那樣，在一線 ROS 陽性肺癌中批准 Augtyro，以及推進我們的關鍵平台，包括為我們的細胞治療計劃啟動多發性硬化症的CD19 NEX-T 研究，並顯示來自我們的靶向蛋白質降解平台的AR-LDD 前列腺[測定] 的早期但重要的I 期數據。

Importantly, we've been active in business development. Specifically, we further diversified our oncology portfolio with targeted oncology assets such as Krazati and PRMT5 from the recently completed Mirati acquisition, the planned addition of a differentiated bispecific ADC from SystImmune with exciting Phase I data across tumors, including lung and breast cancers, and the planned acquisition of RayzeBio bringing important radiopharmaceutical assets, pipeline and manufacturing capabilities.

重要的是，我們一直積極致力於業務發展。具體來說，我們透過最近完成的Mirati 收購中的Krazati 和PRMT5 等目標腫瘤資產進一步豐富了我們的腫瘤產品組合，計劃增加來自SystImmune 的差異化雙特異性ADC，該產品具有跨腫瘤（包括肺癌和乳癌）的令人興奮的I 期數據，以及計劃收購 RayzeBio，帶來重要的放射性藥物資產、管道和製造能力。

And we announced the planned acquisition of Karuna Therapeutics, bringing KarXT, which we believe will be a transformational medicine for patients with schizophrenia, Alzheimer's psychosis and potentially other indications with multibillion-dollar sales potential. We are looking forward to launching this medicine after closing the transaction later this year. These deals add important growth substrate to our company and diversify our portfolio for the long term.

我們也宣布計劃收購 Karuna Therapeutics，帶來 KarXT，我們相信這將成為治療精神分裂症、阿茲海默症和其他潛在適應症患者的轉化藥物，具有數十億美元的銷售潛力。我們期待在今年稍後完成交易後推出該藥物。這些交易為我們公司增添了重要的成長基礎，並使我們的投資組合長期多元化。

Let's turn to Slide 9. Execution for me is a top priority. Starting with commercial. The focus is on continuing to accelerate performance for key growth drivers. This means ensuring the right resourcing and investment levels across our most important brands, and it means having the best people and driving accountability for delivering results.

讓我們轉向幻燈片 9。執行對我來說是重中之重。從商業開始。重點是持續提高關鍵成長動力的績效。這意味著確保我們最重要的品牌擁有正確的資源和投資水平，也意味著擁有最優秀的人才並推動交付成果的責任。

In R&D, building on the momentum, I described coming out of last quarter. As we highlighted at our R&D Day, we have a strong pipeline with the potential to deliver over 16 NMEs through the late 2020s. And here, we need to accelerate and deliver top-tier productivity. We are also taking a hard look at our pipeline to prioritize investments for projects with higher return opportunities and discontinuing lower priority programs.

在研發方面，我描述了上季的發展動能。正如我們在研發日所強調的那樣，我們擁有強大的研發管線，有潛力在 2020 年代末交付超過 16 個 NME。在這裡，我們需要加速並提供頂級生產力。我們也正在認真審視我們的管道，優先投資回報機會較高的項目，並停止優先順序較低的項目。

And to our OpEx base. As we told you, we are going to absorb the OpEx from Karuna. This means we need to make room for these assets by focusing our OpEx base to increase efficiency and productivity. We have begun executing across all 3 fronts, and look forward to updating you on our progress in future quarters. We plan to grow our business this year as shown on Slide 10. David will provide much more detail on our guidance in a few minutes.

以及我們的營運支出基地。正如我們告訴過你的，我們將吸收卡魯納的營運支出。這意味著我們需要透過專注於營運支出基礎來提高效率和生產力，為這些資產騰出空間。我們已開始在所有三個方面執行，並期待向您通報我們未來幾季的最新進展。我們計劃今年發展我們的業務，如幻燈片 10 所示。David 將在幾分鐘內提供有關我們指導的更多詳細資訊。

But what's important from my perspective is that getting our long-term plan to work requires us to deliver well in the short term. A few weeks ago, I reaffirmed our long-term targets as of that date. At that time, I also said we were going back to our historical practice of providing mainly annual guidance with total company rather than product-level revenue targets. Therefore, we will not be updating those long-term targets moving forward. With that in mind, you can see that our growth portfolio is strengthening and our guidance reflects expected top line growth this year.

但從我的角度來看，重要的是要讓我們的長期計畫發揮作用，我們需要在短期內取得良好的成果。幾週前，我重申了我們截至該日的長期目標。當時，我還表示，我們將回到過去的做法，主要提供公司整體的年度指導，而不是產品層面的收入目標。因此，我們不會更新這些長期目標。考慮到這一點，您可以看到我們的成長投資組合正在加強，我們的指導反映了今年的預期收入成長。

Before I hand the call over to David, I would like to thank my BMS colleagues for their efforts at serving patients during 2023 and for their enthusiasm for embarking on our next chapter as a company. David?

在將電話轉交給 David 之前，我要感謝 BMS 的同事在 2023 年為病患服務所做的努力，以及他們對開啟公司下一個篇章的熱情。大衛？

Thank you, Chris, and thank you all again for joining our call today. As Chris mentioned, this is an important time for BMS as we embark on our next chapter, transforming our portfolio. Our performance in 2023 reflect the continued strong growth of our in-line and new product portfolio, and the ongoing erosion of Revlimid.

謝謝克里斯，並再次感謝大家今天加入我們的電話會議。正如 Chris 所提到的，對於 BMS 來說，這是一個重要的時刻，因為我們將開啟我們的新篇章，轉變我們的產品組合。我們 2023 年的業績反映了我們的內嵌產品和新產品組合的持續強勁增長，以及來那度胺 (Revlimid) 的持續侵蝕。

Let's get started with our top line performance on Slide 12. Unless otherwise stated, all comparisons are made versus the same period in 2022, and sales performance growth rates will be discussed on an underlying basis, which excludes the impact of foreign exchange. We delivered sales of approximately $45 billion in 2023, which reflected 8% growth from our in-line and new product portfolio, offset by unfavorable impact of generic entries.

讓我們從投影片 12 上的營收業績開始。除非另有說明，所有比較均與 2022 年同期進行，並將在基本基礎上討論銷售業績成長率，其中排除了外匯的影響。 2023 年，我們的銷售額約為 450 億美元，反映出我們的內嵌產品和新產品組合成長了 8%，但被仿製藥的不利影響所抵消。

During the year, we saw continued strong demand for our key in-line products such as Eliquis and Opdivo, while new products gained traction in their respective markets. If you turn to Slide 13, you see our 2023 sales split between legacy and growth portfolio that Chris spoke about earlier. This is how we will report our business as we move forward. What I can tell you is the transition of the business is already well underway from our legacy to our growth portfolio.

在這一年中，我們看到對 Eliquis 和 Opdivo 等主要係列產品的需求持續強勁，而新產品在各自市場上獲得了關注。如果您翻到投影片 13，您會看到 Chris 先前談到的 2023 年銷售額在傳統產品組合和成長產品組合之間的分配。這就是我們在前進過程中報告業務的方式。我可以告訴您的是，業務從傳統業務轉變為成長業務的轉型已經順利進行。

For 2023, our growth portfolio delivered approximately 15% growth. This supports our strategy that Chris discussed earlier. We see our legacy portfolio providing a solid foundation for cash flow generation in the near term, while the products within our growth portfolio grow in significance. Let me dive deeper into our fourth quarter and full year sales performance starting with our oncology portfolio on Slide 14.

2023 年，我們的成長投資組合實現了約 15% 的成長。這支持了克里斯之前討論的我們的策略。我們看到我們的傳統投資組合為短期內產生現金流奠定了堅實的基礎，而我們的成長投資組合中的產品的重要性也在不斷增長。讓我從投影片 14 上的腫瘤產品組合開始，更深入地介紹我們第四季和全年的銷售業績。

We are pleased with the robust demand for Opdivo, which achieved strong global sales growth for the year. In the fourth quarter, U.S. sales grew 12%, primarily driven by increased volume in core indications, including first-line lung, upper GI and adjuvant bladder cancer, partially offset by optimized growth in first-line melanoma.

我們對 Opdivo 的強勁需求感到高興，該產品今年實現了強勁的全球銷售成長。第四季度，美國銷售額成長 12%，主要受到核心適應症銷量增加的推動，包括一線肺癌、上消化道癌和輔助膀胱癌，但部分被一線黑色素瘤的優化增長所抵消。

During the quarter, U.S. and international markets each benefited from approximately $50 million of favorable stocking. Internationally, sales grew 4%, led by increased demand for lung and gastric cancer indications and from expanded reimbursement.

本季度，美國和國際市場分別受益於約 5,000 萬美元的有利庫存。在國際上，由於肺癌和胃癌適應症的需求增加以及報銷範圍擴大，銷售額增加了 4%。

Turning to Opdualag, which more than doubled its full year sales in 2023 and it's now a standard of care treatment in first-line melanoma. In the fourth quarter, U.S. sales grew 80% versus the prior year and 15% sequentially, benefiting from its strong market share position. With respect to sales of Augtyro in the fourth quarter, we launched in late November and upon U.S. approval and Q4 sales reflecting initial wholesaler stocking. During 2024, we look forward to bringing this important medicine to more patients.

說到 Opdualag，它的全年銷售額在 2023 年增長了一倍多，現在已成為一線黑色素瘤的護理治療標準。受益於其強勁的市場份額地位，第四季度美國銷售額同比增長 80%，環比增長 15%。關於 Augtyro 第四季的銷售情況，我們於 11 月底在美國批准後推出，第四季度的銷售反映了最初的批發商庫存。 2024年，我們期待將這種重要的藥物帶給更多患者。

Let's turn to our cardiovascular on Slide 15. Eliquis generated over $12 billion in sales in 2023 and continues to be the #1 oral anticoagulant globally. In fourth quarter, sales grew, primarily driven by demand in the U.S. as we continue to gain market share from competitors. Internationally, sales in Q4 were broadly flat, driven by generic entry in several European markets.

讓我們轉向幻燈片 15 上的心血管疾病。Eliquis 在 2023 年的銷售額超過 120 億美元，並且仍然是全球排名第一的口服抗凝血藥物。第四季度，銷售成長，主要受到美國需求的推動，因為我們繼續從競爭對手那裡獲得市場份額。在國際上，受多個歐洲市場仿製藥進入的推動，第四季度的銷售額基本持平。

Sales of Camzyos in the fourth quarter and full year were strong, including $88 million in Q4. As of December 31, we had roughly 4,500 patients on commercial drug. And on average, we have been adding roughly 1,000 patients to commercial drug per quarter. The momentum in the U.S. for Camzyos is expected to continue in 2024. And internationally, we expect modest near-term sales contribution based on timing of reimbursement in newly launched market.

Camzyos 第四季和全年的銷售額強勁，其中第四季為 8,800 萬美元。截至 12 月 31 日，我們約有 4,500 名患者正在服用商業藥物。平均而言，我們每季都會增加約 1,000 名患者使用商業藥物。 Camzyos 在美國的成長動能預計將在 2024 年持續下去。在國際上，我們預計基於新推出市場的報銷時間，近期銷售貢獻不大。

Turning to our hematology portfolio performance on Slide 16, starting with Revlimid. Global sales for the full year were approximately $6 billion. Looking forward, we anticipate continued variability in Revlimid sales quarter-to-quarter based upon historic patterns in specialty pharmacy dispensing. We anticipate an additional volume of U.S. generics to enter the market in March. We continue to forecast a step-down in Revlimid revenues in the range of $1.5 billion to $2 billion this year.

轉向幻燈片 16 上我們的血液學產品組合的表現，從 Revlimid 開始。全年全球銷售額約 60 億美元。展望未來，根據專業藥局配藥的歷史模式，我們預期來那度胺的銷售額每季都會持續變化。我們預計三月將有更多的美國仿製藥進入市場。我們繼續預測今年 Revlimid 的營收將下降 15 億至 20 億美元。

Now moving to Reblozyl. Global sales grew 40% in 2023, surpassing $1 billion on an annualized basis for the first time. For the quarter, Reblozyl generated 60% sales growth driven by strong demand and supported by a broad U.S. first-line label. Sales grew 75% in the U.S. in Q4. Internationally, Reblozyl continues to be launched in different markets across the globe, including recently in Japan.

現在搬到Reblozyl。 2023 年全球銷售額成長 40%，年化銷售額首次超過 10 億美元。在強勁需求的推動和廣泛的美國一線品牌的支持下，Reblozyl 本季銷售額成長了 60%。第四季美國銷售額成長 75%。在國際上，Reblozyl 繼續在全球不同市場推出，包括最近在日本。

Turning to our cell therapy portfolio, starting with sales of Abecma in the U.S., we continue to experience competitive impacts. While ex-U.S., demand remained strong in the quarter. We remain focused on demonstrating the benefits of the product profile to our customers' anticipation of expanded use in the U.S. upon the potential approval of KarMMA-3 data in third line plus setting. Abecma was recently approved in Japan in the third-line setting based on KarMMa-3 data. And last week, we received positive CHMP opinion.

談到我們的細胞治療產品組合，從 Abecma 在美國的銷售開始，我們繼續遭受競爭影響。除美國外，本季需求依然強勁。我們仍然專注於向我們的客戶展示產品簡介的好處，以期在 KarMMA-3 數據在三線及以上環境中獲得潛在批准後在美國擴大使用。 Abecma 最近根據 KarMMa-3 數據在日本獲得批准用於三線治療。上週，我們收到了 CHMP 的正面意見。

Moving to Breyanzi. Global sales doubled year-over-year, reflecting the strength of its clinical profile and an improved manufacturing capacity. We are pleased to have received FDA priority review for all 3 of our expanded indications for Breyanzi and look forward to the PDUFA date in March for chronic lymphocytic leukemia and additional PDUFA dates in May for follicular and mantle cell lymphoma indications. Looking to this year, we expect to see strong sales growth starting in the second quarter, driven by improved supply capacity and the potential for these new additional indications.

搬到布雷揚齊。全球銷售額較去年同期翻了一番，反映出其臨床實力和生產能力的提高。我們很高興獲得 FDA 對 Breyanzi 的所有 3 個擴展適應症的優先審查，並期待 3 月份慢性淋巴細胞白血病的 PDUFA 日期和 5 月份濾泡和套細胞淋巴瘤適應症的額外 PDUFA 日期。展望今年，我們預計在供應能力改善和這些新的附加適應症的潛力的推動下，第二季將出現強勁的銷售成長。

Moving to immunology on Slide 17. Global sales of Zeposia in 2023 grew 72% to $434 million, driven by increased demand in multiple sclerosis and ulcerative colitis. We remain focused on driving growth across both indications. For 2024, keep in mind the typical impact of U.S. Zeposia sales in the first quarter due to copay assistance for commercially insured patients who benefits reset.

轉向幻燈片 17 上的免疫學。由於多發性硬化症和潰瘍性結腸炎的需求增加，Zeposia 的全球銷售額在 2023 年增長了 72%，達到 4.34 億美元。我們仍然專注於推動這兩種適應症的成長。對於 2024 年，請記住美國 Zeposia 第一季銷售的典型影響，這是由於對福利重置的商業保險患者提供共付額援助。

With Sotyktu, our goal continues to be driving demand and broadening access. We made good progress on both fronts in the fourth quarter. Fourth quarter sales in the U.S. also benefited from a clinical supply purchase of $17 million. When you strip out the onetime purchases in Q4 and Q3, we showed strong underlying sequential sales growth of approximately 40%, reflecting good pull-through from CVS and increased demand. Going forward, the way to look at our progress in the U.S. is through commercially paid prescriptions.

對於 Sotyktu，我們的目標仍然是推動需求和擴大覆蓋範圍。第四季我們在兩方面都取得了良好進展。美國第四季的銷售額也受惠於 1700 萬美元的臨床供應採購。當你剔除第四季和第三季的一次性採購時，我們發現潛在的連續銷售成長強勁，約為 40%，反映出 CVS 的良好拉動和需求的增加。展望未來，我們將透過商業付費處方來看待我們在美國的進展。

As we build volume and improve access, we will be subject to higher rebates, which is something to keep in mind as you model Sotyktu for 2024. Of course, Adam can talk more about this in the Q&A portion of our call today. Internationally, we expect Sotyktu to gain additional country regulatory and reimbursement approvals over time.

隨著我們增加銷量並提高訪問量，我們將獲得更高的回扣，這是在為2024 年構建Sotyktu 模型時要記住的事情。當然，Adam 可以在我們今天電話會議的問答部分中詳細討論這一點。在國際上，我們預計 Sotyktu 隨著時間的推移將獲得更多國家監管和報銷批准。

Switching gears to our fourth quarter P&L on Slide 18. Having just covered sales performance, let me walk through a few non-GAAP key line items. Gross margin as a percentage of sales decreased approximately 150 basis points to 76.4% compared to prior year due to product mix and lower hedge settlement gains. Excluding acquired in-process R&D, fourth quarter and full year operating expenses decreased primarily due to timing of expenses in 2022. The fourth quarter decline was partially offset by increased investments in Camzyos, Sotyktu and the timing of pipeline investments. Acquired in-process R&D in the quarter was $600 million, which was partially offset by licensing income, resulting in an unfavorable net impact of $0.20 of EPS. The fourth quarter effective tax rate was approximately 14.9%, driven primarily by earnings mix. Overall, earnings per share was $1.70 in the quarter and $7.51 for the full year.

切換到投影片 18 上的第四季損益表。剛剛介紹了銷售業績，讓我來介紹一下一些非 GAAP 關鍵項目。由於產品組合和避險結算收益下降，毛利率佔銷售額的百分比比上年下降約 150 個基點至 76.4%。不包括收購的正在進行的研發，第四季度和全年營運費用下降主要是由於 2022 年的費用安排。第四季度的下降被 Camzyos、Sotyktu 投資的增加和管道投資的時間安排部分抵消。本季度獲得的正在進行的研發費用為 6 億美元，部分被授權收入抵消，導致每股收益 0.20 美元的不利淨影響。第四季有效稅率約為 14.9%，這主要是由獲利組合推動的。總體而言，本季每股收益為 1.70 美元，全年每股收益為 7.51 美元。

Now moving to the balance sheet and capital allocation on Slide 19. Our financial position remains strong. With approximately $12.6 billion in cash and marketable securities on hand as of December 31, as we generate cash flow from operations of $4.3 billion in the fourth quarter. Through our strong financial discipline, we have been able to invest in our business and further expand our portfolio, maintain strong operating margins, pay down debt and return significant cash to shareholders through share repurchases and dividends.

現在轉向投影片 19 上的資產負債表和資本配置。我們的財務狀況依然強勁。截至 12 月 31 日，我們手頭現金和有價證券約為 126 億美元，第四季度營運產生的現金流為 43 億美元。透過我們強大的財務紀律，我們能夠投資於我們的業務並進一步擴大我們的投資組合，保持強勁的營業利潤率，償還債務並透過股票回購和股息向股東返還大量現金。

Over the past 3 years, we've returned over $30 billion in shareholder distributions, including the dividend, which we've increased annually for 15 years in a row. As you know, we're going to be taking on additional debt this year to finance our planned acquisitions of Karuna and RayzeBio. However, with our strong financial position, we plan to utilize our cash flow to pay down our debt as we demonstrated in the past. Our plan is to repay approximately $10 billion of debt over the next 2 years to improve our leverage profile.

在過去 3 年裡，我們返還了超過 300 億美元的股東分配，其中包括股息，我們連續 15 年每年增加股息。如您所知，我們今年將承擔額外的債務，為我們計劃收購 Karuna 和 RayzeBio 提供資金。然而，憑藉我們強勁的財務狀況，我們計劃利用現金流來償還債務，正如我們過去所展示的那樣。我們的計劃是在未來 2 年內償還約 100 億美元的債務，以改善我們的槓桿狀況。

Before turning to our line item guidance, let me close with our 2024 non-GAAP guidance on Slide 20. We which includes Mirati, but excludes the future impact of pending transactions, SystImmune, Karuna and RayzeBio. As we did in 2023, we were providing revenue guidance on a reported basis as well as on an underlying basis, which assumes currency remains consistent with prior year. We expect 2024 revenues to increase in a low single-digit range, reflecting our confidence in the growing momentum of our growth portfolio. Excluding foreign exchange, we expect revenues to increase in the low single digit as well.

在轉向我們的訂單項目指南之前，讓我以投影片 20 上的 2024 年非 GAAP 指南作為結束語。我們包括 Mirati，但不包括未決交易、SystImmune、Karuna 和 RayzeBio 的未來影響。正如我們在 2023 年所做的那樣，我們在報告的基礎上以及基礎上提供收入指引，假設貨幣與上一年保持一致。我們預計 2024 年營收將在較低的個位數範圍內成長，反映出我們對成長投資組合成長動能的信心。不包括外匯，我們預期收入也將以較低的個位數成長。

Driving our momentum this year, we will be increasing the sales in our growth portfolio from products like Opdivo and our recently launched products. As we said previously, we expect a more modest pace of growth than last year for Opdivo with the potential for acceleration in the back half of the year from new indications. And while our legacy portfolio includes assets that are maturing, we expect strong growth from Eliquis in the U.S. this year. As it relates to quarterly progression of our sales, a few reminders.

為了推動今年的發展勢頭，我們將增加 Opdivo 等產品和我們最近推出的產品的成長產品組合的銷售。正如我們之前所說，我們預計 Opdivo 的成長速度將比去年更為溫和，但新適應症有可能在今年下半年加速成長。雖然我們的傳統投資組合包括正在成熟的資產，但我們預計今年 Eliquis 在美國的強勁成長。由於它與我們銷售的季度進展有關，因此有一些提醒。

For products like Revlimid, Pomalyst and Camzyos, keep in mind the typical impact on sales in the first quarter due to patients entering the Medicare coverage gap early in the year. And for Eliquis, the coverage gap dynamic works in the opposite direction where we expect sales in the first half of the year to be higher than in the second half. As it relates to our line item guidance for the year, we expect gross margin to be approximately 74%, which reflects an evolution of our sales mix and the nonrecurrence of hedging gains from last year.

對於 Revlimid、Pomalyst 和 Camzyos 等產品，請記住，由於患者在年初進入醫療保險覆蓋缺口，對第一季銷售的典型影響。對於 Eliquis 來說，覆蓋範圍差距動態的作用與我們預計上半年的銷售額高於下半年的相反。由於這與我們今年的訂單項目指導相關，我們預計毛利率約為 74%，這反映了我們銷售組合的演變以及去年的對沖收益不再重複。

Excluding in-process R&D, we expect our total operating expenses to increase in a low single-digit range, reflecting the additional cost of Mirati and the reallocation of costs and efficiency initiatives in MS&A as we continue to invest in our new product launches. This aligns with our previous operating margin target of at least 37%. This means we will remain focused on driving operational efficiencies across the organization including portfolio prioritization to enable us to invest for growth while maintaining high productivity.

不包括過程中的研發，我們預計我們的總營運費用將在較低的個位數範圍內增長，反映出隨著我們繼續投資於新產品的推出，Mirati 的額外成本以及MS&A 成本和效率計劃的重新分配。這與我們之前至少 37% 的營業利潤率目標一致。這意味著我們將繼續專注於提高整個組織的營運效率，包括投資組合優先級，以使我們能夠在保持高生產力的同時進行成長投資。

We expect OI&E to be approximately $250 million of income, reflecting the PD-1 (inaudible) step down in January from 6.5% to 2.5%, as well as the financing costs related to the Mirati acquisition. We project our tax rate to be approximately 17.5%, reflecting an increase due to nonrecurrence of onetime tax benefit that occurred in the third quarter of last year, plus the anticipated impact of Pillar 2.

我們預期 OI&E 的營收約為 2.5 億美元，反映出 1 月 PD-1（聽不清楚）從 6.5% 降至 2.5%，以及與 Mirati 收購相關的融資成本。我們預計稅率約為 17.5%，反映了去年第三季發生的一次性稅收優惠不再重複而導致的成長，加上第二支柱的預期影響。

Finally, we expect to deliver non-GAAP earnings per share within the range of $7.10 and $7.40. For clarity, our 2024 guidance excludes the 3 pending transactions. As a reminder, SystImmune is expected to add about $800 million in in-process R&D. Karuna is expected to be about $0.30 dilutive to earnings relating to financing costs as we plan to absorb the OpEx. And RayzeBio would be approximately $0.13 relative to earnings, with half in financing and the other half in OpEx.

最後，我們預計非 GAAP 每股盈餘將在 7.10 美元至 7.40 美元之間。為清楚起見，我們的 2024 年指引不包括 3 筆待處理交易。需要提醒的是，SystImmune 預計將在研發中增加約 8 億美元。由於我們計劃吸收營運支出，預計卡魯納將稀釋與融資成本相關的收益約 0.30 美元。 RayzeBio 的收益約為 0.13 美元，其中一半用於融資，另一半用於營運支出。

When we report in Q1 in April, we will update our guidance to reflect the deals that have closed at that time. Before we move to the question-and-answer session, I want to thank all of our colleagues around the world for their hard work and dedication in 2023. This is an exciting time for BMS as we write a new chapter and maintain a singular focus on improving our growth profile over the course of the decade. I believe that our focused financial discipline, coupled with strong cash flow generation, are key advantages that will enable us to further diversify our portfolio and invest in growth opportunities to deliver for patients and our investors.

當我們在四月的第一季報告時，我們將更新我們的指導，以反映當時已完成的交易。在我們進入問答環節之前，我要感謝世界各地的所有同事在 2023 年的辛勤工作和奉獻精神。對於 BMS 來說，這是一個激動人心的時刻，我們將譜寫新篇章並保持專注改善我們在過去十年中的成長狀況。我相信，我們專注的財務紀律，加上強大的現金流生成，是關鍵優勢，使我們能夠進一步實現投資組合多元化，並投資於成長機會，為患者和投資者提供服務。

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

我現在將把電話轉回蒂姆和克里斯進行問答。

First question, please. But before we do, just a reminder, it's obviously a busy morning for everybody. And to the extent you can keep to just one question so we can get to as many people as possible, we would appreciate that. So let's go to our first rest question, please.

第一個問題，請。但在此之前，先提醒一下，這顯然對每個人來說都是一個忙碌的早晨。如果您能只提出一個問題，以便我們能夠接觸到盡可能多的人，我們將不勝感激。那麼，讓我們來討論第一個休息問題。

The first question will come from Luisa Hector of Berenberg.

第一個問題將由貝倫貝格的路易莎·赫克托提出。

Maybe I'll start with the Abecma because you have the FDA AdCom coming up. So just your level of confidence heading into that. Any comments on how the label changes are impacting or not for all CAR-Ts? And just any pressure that you're seeing from CAR-T4 and how that might evolve in 2024?

也許我會從 Abecma 開始，因為 FDA AdCom 即將到來。所以只是你對此的信心程度。對於標籤變化對所有 CAR-T 有何影響有何評論？您從 CAR-T4 看到的壓力以及 2024 年可能會如何演變？

First, we'll have Samit answer and then go to Adam.

首先，我們讓薩米特回答，然後去找亞當。

Thank you, Luisa, for the question. From Abecma perspective, KarMMa-3 data, we've shared updated data at ASH last year. And as you saw, it was very clear what is driving the overall survival curves. It's because of the crossover that the patients have allowance for the progression of their disease on the standard of care arm. And therefore, that curve does benefit, and therefore, you see much of an impact on that overall survival benefit that these patients are getting.

謝謝你，路易莎的提問。從 Abecma 的角度來看，KarMMa-3 數據，我們去年在 ASH 上分享了更新的數據。正如您所看到的，整體生存曲線的驅動因素非常清楚。由於交叉，患者在標準護理組中可以享受疾病進展的津貼。因此，這條曲線確實有益，因此，您會看到這些患者獲得的整體生存效益受到很大影響。

We are very confident and we are very much looking forward to having that dialogue and discussion with the regulatory authorities and looking forward to getting this product to the patients as soon as possible. So the second part that you asked about, the label updates that the FDA is seeking right now for all CAR-T products around T cell malignancies. Once again, we've treated thousands of patients. And from our perspective, as we look into our data, we do not see a causative relationship to CAR-T cell therapies in terms of Breyanzi and Abecma. So we'll continue to have the dialogue with the regulators on that as well as we look to the final wording that the FDA will decide. With that, let me pass it on to Adam?

我們非常有信心，非常期待與監管機構進行對話和討論，並期待盡快將這個產品送到患者手中。所以你問的第二部分是 FDA 目前正在尋求針對 T 細胞惡性腫瘤的所有 CAR-T 產品的標籤更新。我們再一次治療了數千名患者。從我們的角度來看，當我們研究數據時，我們沒有看到 Breyanzi 和 Abecma 與 CAR-T 細胞療法之間的因果關係。因此，我們將繼續與監管機構就此進行對話，並期待 FDA 決定的最終措辭。那麼，讓我把它轉達給亞當吧？

Thanks, Luisa, for the question. So we do expect growth in 2024 for Abecma. KarMMa-3 is a key catalyst for growth this year. And as Samit said, we do look forward to the ODAC to reinforce the benefits of Abecma in a triple exposed patient population.

謝謝路易莎的提問。因此，我們確實預計 Abecma 將在 2024 年實現成長。 KarMMa-3 是今年成長的關鍵催化劑。正如 Samit 所說，我們確實期待 ODAC 加強 Abecma 在三重暴露患者群體中的益處。

As you can imagine, our commercial teams have been launch-ready for some time, and we're also seeing continued strong international performance. And we'll launch both, Abecma and Breyanzi in a number of new countries this year. We have stated that we've seen continued impact from additional BCMA agents. This is a highly competitive market, putting some pressure on Abecma growth, but our teams are squarely focused on opening new accounts, expanding our site's footprint, not just internationally, but also in the U.S. And quoting the gap on efficacy perceptions, including solidifying any misconceptions around Abecma's efficacy and reinforcing Abecma's safety profile, particularly as it relates to CNS neurotoxicity.

正如您可以想像的那樣，我們的商業團隊已經為發布做好了一段時間的準備，而且我們也看到了持續強勁的國際表現。今年我們將在一些新的國家推出 Abecma 和 Breyanzi。我們已經聲明，我們已經看到其他 BCMA 代理商的持續影響。這是一個競爭激烈的市場，給Abecma 的成長帶來了一些壓力，但我們的團隊專注於開設新帳戶，擴大我們網站的足跡，不僅在國際上，而且在美國。並引用功效認知上的差距，包括鞏固任何對 Abecma 功效和加強 Abecma 安全性的誤解，特別是因為它與 CNS 神經毒性有關。

So taking together, we're confident in Abecma's profile. Looking forward to the ODAC, and I'm confident that we'll be more competitive this year.

綜上所述，我們對 Abecma 的形象充滿信心。期待 ODAC，我相信今年我們會更具競爭力。

The next question comes from Chris Schott of JPMorgan.

下一個問題來自摩根大通的克里斯·肖特。

So maybe a bigger picture question on the new launches. I think those new launches did about $3.6 billion in 2023. And I know you're not giving longer-term targets. But just any just rough framework of how to think about those sales in 2024? I guess is there a target you're providing? If there's not a target, can you maybe just talk a little bit about any areas you see that maybe you're more or less optimistic versus where Street consensus is? I know there's quite a bit of focus on the trajectory of those ramps.

所以也許是關於新產品發布的更大的問題。我認為這些新產品的推出在 2023 年帶來了約 36 億美元的收入。而且我知道你們沒有給出長期目標。但是，有一個關於如何思考 2024 年銷售情況的粗略框架嗎？我想你有提供目標嗎？如果沒有目標，您能否簡單談談您所看到的與華爾街共識相比您或多或少樂觀的領域？我知道人們非常關注這些坡道的軌跡。

Thanks for the question, Chris. Maybe I'll just start very quickly and then I'll turn it over to Adam. As we had mentioned, we're not going to be providing individual product level guidance, and I think we had alluded to that when we met at JPMorgan 3 weeks ago.

謝謝你的提問，克里斯。也許我很快就會開始，然後把它交給亞當。正如我們所提到的，我們不會提供單獨的產品等級指導，我想我們三週前在摩根大通會面時已經提到過這一點。

But we did give and we'll continue to give company line item guidance as we did today. And then you'll see, as we reported today, we're going to be talking additionally about the growth portfolio that we have, which is going to be important as we think about the business going forward. Adam, do you want to talk about the new launches?

但我們確實提供了並將繼續像今天一樣提供公司訂單項指導。然後你會看到，正如我們今天報導的那樣，我們將另外討論我們擁有的成長投資組合，這在我們考慮未來業務時非常重要。 Adam，你想談談新產品的發布嗎？

Yes. So thanks for the question, Chris. I mean, we're coming off a good quarter, and we have a strong foundation for growth to build upon. We're focused on continuing to accelerate our new product portfolio and maximizing the 10 launches that we've had over the last 4 years. We're certainly prioritizing the execution of our new launches and adding investment to accelerate the performance of our growth portfolio for products like Camzyos, Sotyktu and Breyanzi.

是的。謝謝你的提問，克里斯。我的意思是，我們的季度表現不錯，並且我們擁有堅實的成長基礎。我們專注於繼續加速我們的新產品組合，並最大限度地增加過去 4 年來我們發布的 10 次產品。我們當然會優先執行新產品的發布，並增加投資，以加快 Camzyos、Sotyktu 和 Breyanzi 等產品的成長投資組合的表現。

You've also seen strong performance from Reblozyl and Opdualag. We also have some of our growth products like Eliquis and Opdivo, which will continue to contribute significant growth in 2024. And finally, we're readying for the low KarXT in September, which we're excited to launch this product, which will be the first new treatment in decades for schizophrenia and also brings a multibillion-dollar opportunity to the organization. So adding it up, that's why we're excited to continue to drive commercial performance in an important 2024.

您還看到了 Reblozyl 和 Opdualag 的強勁表​​現。我們還有一些成長產品，如Eliquis 和Opdivo，它們將在2024 年繼續貢獻顯著成長。最後，我們正在為9 月的低KarXT 做好準備，我們很高興推出這款產品，該產品將在2024年推出。這是幾十年來第一個針對精神分裂症的新療法，也為該組織帶來了數十億美元的機會。因此，這就是為什麼我們很高興能夠在重要的 2024 年繼續推動商業業績。

The next question comes from Chris Shibutani of Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

This is Charlie on for Chris. We had a question on the subcutaneous Opdivo strategy for a potential launch there. We heard from one of your competitors yesterday out there. Potential for a subcutaneous [CPI] where they were considering what sounded like a careful pricing strategy in the context of potential intravenous biosimilars that could be on the market at the same time. So just wondering how you're thinking about pricing on the potential of subcutaneous Opdivo?

這是查理為克里斯代言的。我們對皮下注射 Opdivo 的潛在上市策略有疑問。昨天我們收到了你們一位競爭對手的來信。皮下注射 [CPI] 的潛力，他們正在考慮在可能同時上市的潛在靜脈注射生物相似藥的背景下採取聽起來謹慎的定價策略。所以想知道您如何考慮皮下注射 Opdivo 的潛力定價？

Adam?

亞當？

Yes. Thanks, Charlie, for the question. So we're not going to comment on the pricing of subcu. But what I can say, we announced positive results of our subcu Opdivo study in the quarter, and we anticipate a launch early next year. As a result, we have the opportunity to potentially benefit thousands of patients well into the next decade with subcu Opdivo.

是的。謝謝查理的提問。所以我們不會對 subcu 的定價發表評論。但我可以說的是，我們在本季宣布了 subcu Opdivo 研究的正面結果，我們預計明年初推出。因此，我們有機會透過 subcu Opdivo 在未來十年內使數千名患者受益。

I think an important thing to keep in mind. Remember, subcu has the potential to address the treatment burden for both patients and physicians due to less than 5-minute infusion time. And we talked about our ability to convert roughly 30% to 40% of the overall U.S. Opdivo business into subcu. And that's why we would expect to see this franchise endure into the next decade. So we certainly look forward to bringing this important formulation, both to patients and physicians.

我認為要記住一件重要的事情。請記住，由於輸注時間不到 5 分鐘，subcu 有可能減輕患者和醫生的治療負擔。我們也談到了我們將美國 Opdivo 業務的大約 30% 至 40% 轉化為 subcu 的能力。這就是為什麼我們希望看到這個特許經營權持續到下一個十年。因此，我們當然期待將這項重要的配方帶給患者和醫生。

The next question comes from Andrew Baum of Citi.

下一個問題來自花旗銀行的安德魯·鮑姆。

A question for Adam. Have you rethought the use of bridge programs for launches in the U.S. following your Sotyktu experience? And then same topic. Realistically, how long do you think it will be before Sotyktu starts printing revenues through the combination of broader coverage as well as just getting these patients off the bridge?

問亞當一個問題。根據您的 Sotyktu 經驗，您是否重新考慮在美國發佈時使用橋樑計劃？然後是同樣的話題。實際上，您認為 Sotyktu 需要多長時間才能開始透過更廣泛的覆蓋範圍以及讓這些患者擺脫困境來增加收入？

Great. Thanks, Andrew. Let me just take the second question first, and then I'll answer as well the bridge question. So Sotyktu is an important brand for the organization, and we are executing against our plan. We shared last year, we're focused on 2 areas. The first is driving demand at the top of the funnel. And the second is securing access and of course, as you mentioned, pulling through those patients from bridge to commercial. And we're making progress against both.

偉大的。謝謝，安德魯。我先回答第二個問題，然後再回答橋接問題。因此，Sotyktu 是該組織的一個重要品牌，我們正在按照我們的計劃執行。我們去年分享過，我們專注於兩個領域。首先是推動漏斗頂部的需求。第二個是確保准入，當然，正如您所提到的，將這些患者從橋樑帶到商業區。我們在這兩方面都取得了進展。

You heard from David. When you normalize sales, excluding clinical trial, orders, net sales increased to about 40% versus Q3 and access is critically important in this highly competitive market to drive commercial sales. So we secured ESI and now Cigna in a one-step position. That adds another 40 million lives approximately to complement CVS which represent zero-step position, will continue to be this year and that's approximately 25 million lives.

你收到大衛的來信了。當銷售正常化時（不包括臨床試驗、訂單），淨銷售額與第三季相比增加至 40% 左右，在這個競爭激烈的市場中，准入對於推動商業銷售至關重要。因此，我們確保了 ESI，現在 Cigna 處於一步到位的位置。這增加了約 4000 萬人的生命，以補充代表零步位置的 CVS，今年將繼續，約 2500 萬人的生命。

And we are actively negotiating with other payers and look forward to updating you on additional progress in due course. This year, it's really important to focus on increased paid commercial prescriptions for Sotyktu. We will continue to build volume in both new patients that are going to move directly on to Sotyktu at the specialty pharmacies, which, quite frankly, becomes easier with the improved access that we have now as well as moving patients out of bridge and onto commercial product.

我們正在積極與其他付款人進行談判，並期待在適當的時候向您通報更多進展。今年，重點關注 Sotyktu 付費商業處方的增加非常重要。我們將繼續增加新患者的數量，這些患者將在專業藥房直接轉移到 Sotyktu，坦率地說，隨著我們現在擁有的通道的改善以及將患者從橋樑轉移到商業藥房，這變得更加容易產品。

David talked about where we are today. But in Q1, we expect to see around 10,000 paid prescriptions for Sotyktu. And he also mentioned there will be an increase in gross net due to broader rebating which was needed to secure improved access that impacts net sales in Q1. But we expect to see good momentum in growing our base of paid prescriptions this year, and we plan to get roughly double that level around 20,000 prescriptions in Q4. And that volume momentum will more than offset the gross to net reset in Q1 as the year progresses.

大衛談到了我們今天的處境。但在第一季度，我們預計 Sotyktu 的付費處方數量約為 10,000 個。他也提到，由於需要更廣泛的回扣，毛淨額將會增加，這是為了確保改善影響第一季淨銷售額的准入。但我們預計今年付費處方數量成長勢頭良好，並計劃在第四季度將處方數量增加一倍，約 20,000 個。隨著今年的進展，這一銷售動能將遠遠抵消第一季總淨值的重置。

As you also asked around conversion. Conversion is going exactly as we expected. We've made very good progress in shifting patients from CVS from the bridge to commercial product. We talked about taking around 2 to 3 months for patients to move from bridge to commercial. And as a result, you saw that 40% sequential growth that excluded the clinical trial purchases. And so we'll continue to drive demand and work to continue to improve moving patients from our bridge with our ESI and Cigna wins in 2024 and also work to secure improved access in 2025 as well, where it makes financial sense to do so.

正如您也詢問了轉換問題。轉換完全按照我們的預期進行。我們在將患者從 CVS 過渡到商業產品方面取得了非常好的進展。我們談到患者從橋樑轉向商業需要大約 2 到 3 個月的時間。結果，您看到了 40% 的環比增長（不包括臨床試驗採購）。因此，我們將繼續推動需求，並努力繼續改善將患者從橋上轉移的情況，並在 2024 年獲得 ESI 和 Cigna 的勝利，並努力確保在 2025 年改善准入，這樣做具有經濟意義。

The next question comes from Seamus Fernandez of Guggenheim Securities.

下一個問題來自古根漢證券公司的謝默斯·費爾南德斯。

So just a quick one here. On Reblozyl, the continued strength of the brand and the acceleration that we're starting to see. Can you just talk about what's driving that incrementally? And maybe give us a little bit of a sense of how we should be thinking about the international opportunity for Reblozyl in particular?

所以這裡只是快速介紹一下。在 Reblozyl 上，我們開始看到品牌的持續實力和加速發展。您能談談是什麼推動了這項成長嗎？也許能讓我們稍微了解一下我們該如何思考 Reblozyl 的國際機會？

Adam?

亞當？

Yes, Seamus, thanks for the question. The first-line MDS launch is progressing very well in the U.S. with strong demand supported by our broad label in an RS-agnostic patient population. Just take you back, we launched in late August. And initially after the launch, we saw rapid switches from ESAs to Reblozyl. But we're now seeing strength in first-line use across RS-positive population, and we're steadily building momentum in the RS-negative patient population, particularly in the community setting where the majority of patients are treated.

是的，謝莫斯，謝謝你的提問。一線 MDS 的上市在美國進展順利，我們在 RS 不可知患者群體中的廣泛標籤支持了強勁的需求。回想一下，我們是在八月下旬推出的。推出後最初，我們看到從 ESA 到 Reblozyl 的快速轉換。但我們現在看到 RS 陽性人群中一線用藥的優勢，並且我們正在 RS 陰性患者人群中穩步建立勢頭，特別是在大多數患者接受治療的社區環境中。

We also have -- after the ASH presentation, we've heard feedback from both academic and community physicians recognizing the durability of response and the ability to remain transfusion independent as key features of the brand. So we're very pleased with the launch as we're seeing strong sales performance, we expect it to continue this year. And Reblozyl was also approved in Japan in mid-January. We're seeing nice uptake there, and we expect European approval in the first half of this year.

在 ASH 演示之後，我們也聽到了學術界和社區醫生的回饋，他們認識到反應的持久性和保持輸血獨立的能力是品牌的關鍵特徵。因此，我們對此次推出感到非常滿意，因為我們看到了強勁的銷售業績，我們預計今年將繼續下去。 Reblozyl 也於 1 月中旬在日本獲得批准。我們看到那裡的應用程式很不錯，我們預計歐洲將在今年上半年獲得批准。

The next question comes from Tim Anderson of Wolfe Research.

下一個問題來自沃爾夫研究中心的蒂姆·安德森。

On Sotyktu, I think it was at Q3, you mentioned it would take longer to get no step edits. So I'm wondering what the current step edits are exactly, what brands do patients have to step through? Is it Otezla primarily? Or is it Humira, either brand or biosimilar or what exactly?

在 Sotyktu 上，我認為是在第三季度，您提到需要更長的時間才能獲得無步驟編輯。所以我想知道目前的步驟編輯到底是什麼，患者必須經歷哪些品牌？主要是奧特茲拉嗎？或是修美樂（Humira），品牌藥還是生物相似藥，或者到底是什麼？

Yes, Tim, thank you. So as I mentioned, we secured additional access at ESI and now Cigna in a one-step position. And so that really is regardless of the product. So that could be a step after Otezla, it could be a step after IL-17s or the IL-23 agents in the market, but what's important is that, that adds another 40 million lives to complement our zero-step adds in CVS. So taking together that's 65 million lives today, and we're continuing to actively negotiate with payers, and we will update you on additional progress over the coming months.

是的，提姆，謝謝你。正如我所提到的，我們在 ESI 獲得了額外的存取權限，現在 Cigna 處於一步到位的狀態。所以這確實與產品無關。因此，這可能是繼Otezla 之後的一步，也可能是繼市場上的IL-17 或IL-23 藥物之後的一步，但重要的是，這又增加了4000 萬人的生命，以補充我們在CVS中的零步驟添加。因此，今天總共有 6500 萬人的生命，我們將繼續積極與付款人談判，我們將在未來幾個月向您通報更多進展。

The next question comes from Trung Hunh of UBS.

下一個問題來自瑞銀的 Trung Hunh。

Just on IRA, I realize there's not much you can say about the negotiation where I think CMS has just sent their initial offer. But I was wondering about more -- how do you think about the impact? So for Eliquis, given the patient mix is largely skewed towards Medicare, do you think there could be a potential uplift that could help offset that pricing erosion? And how do you anticipate the commercial spillover from those pricing impacts?

就 IRA 而言，我意識到您對談判沒有太多可說的，我認為 CMS 剛剛發出了他們的初步報價。但我想知道更多——你如何看待這種影響？因此，對於 Eliquis 來說，考慮到患者結構很大程度上偏向醫療保險，您認為可能存在潛在的提升，有助於抵消價格侵蝕嗎？您如何預測這些定價影響所帶來的商業外溢效應？

Yes. Thanks for the question. I'll take that. So as it relates to IRA, we do expect an improvement in patient affordability as the patient out-of-pocket changes for patients this year and in the next. We will see this more acutely next year as out-of-pocket max is kept at $2,000 and then patients had 0% liability thereafter. So more broadly though, we largely don't expect Medicare-party design changes to impact our portfolio because that will largely take effect in 2026 when branded Revlimid will be fully eroded. As it relates to commercial spillover, I think it's important that we always look at multiple planning scenarios including the risk of spillover, but also the potential opportunity, as I just shared around patient affordability.

是的。謝謝你的提問。我會接受的。因此，就 IRA 而言，隨著今年和明年患者自付費用的變化，我們確實預計患者的負擔能力會有所改善。明年我們會更清楚地看到這一點，因為自付費用最高限額保持在 2,000 美元，此後患者的責任為 0%。但更廣泛地說，我們基本上預計醫療保險方的設計變更不會影響我們的產品組合，因為這將在 2026 年很大程度上生效，屆時 Revlimid 品牌將被完全侵蝕。由於它與商業溢出有關，我認為重要的是我們始終要考慮多種規劃場景，包括溢出風險，但也包括潛在機會，正如我剛剛圍繞患者負擔能力所分享的那樣。

So there are pushes and pulls there with changes in the benefit design. We are going to have to continue to manage potential spillover risk to commercial with the transparency of the MFP price on September 1. But we also do that today as we manage both books of business, and we'll need to continue to remain disciplined across our commercial payers. And at the same time, just because the payer wants to include this in negotiating mix in commercial, it certainly doesn't mean that we have to agree there. So we expect continued strong performance this year for Eliquis in the U.S. and expect significant growth through the end of 2025.

因此，福利設計的改變會帶來推動與拉扯。我們將不得不繼續透過 9 月 1 日 MFP 價格的透明度來管理對商業的潛在溢出風險。但今天，我們在管理兩份業務時也這樣做了，我們需要繼續在整個業務範圍內保持紀律。我們的商業付款人。同時，僅僅因為付款人希望將其納入商業組合談判中，並不意味著我們必須同意這一點。因此，我們預計 Eliquis 今年在美國的業績將繼續強勁，並預計到 2025 年底將顯著成長。

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

下一個問題來自美國銀行的傑夫‧米查姆。

Chris or David, on capital allocation, you guys have some deals closing, obviously, in the first half of this year. But would you say the balance of the year is more of a pause on deals with the focus on integration? Or would bolt-on still be of interest? I'm just trying to get a sense with all the launches operationally and whether newer products or more products and integration could be a distraction to what you're doing commercially?

克里斯或大衛，在資本配置方面，你們顯然在今年上半年完成了一些交易。但您是否認為今年的剩餘時間更多的是暫停交易，並專注於整合？或者螺栓固定仍然會引起人們的興趣嗎？我只是想了解所有營運方面的發布，以及更新的產品或更多的產品和整合是否會幹擾您正在做的商業活動？

Thanks for the question, Geoff. I'll take that one. So as we've discussed previously, as we think about capital allocation, business development continues to be a top priority for us. Obviously, we've just executed a number of deals towards the end of last year, and we've got to stay focused on executing those deals.

謝謝你的提問，傑夫。我會接受那個。正如我們之前討論的，當我們考慮資本配置時，業務發展仍然是我們的首要任務。顯然，我們在去年年底剛剛執行了一些交易，我們必須繼續專注於執行這些交易。

Having said that, we certainly are going to continue to be interested in bringing innovation into the company that makes strategic and financial sense to do so. I would characterize those a bit more as bolt-on opportunities. At this point, we're also, of course, continuing to look at partnerships and licensing deals as well. But that's how I would characterize it. Business development is still a priority.

話雖如此，我們當然會繼續對將創新帶入公司感興趣，這具有戰略和財務意義。我更願意將這些描述為補充性機會。當然，目前我們也持續考慮合作夥伴關係和授權交易。但這就是我對它的描述。業務發展仍是重中之重。

The next question comes from Matt Phipps of William Blair.

下一個問題來自威廉布萊爾的馬特菲普斯。

Samit, I was wondering if you could give us a sense of how many SLE patients do you expect to treat with the NEX-T CAR-T program this year? And is the next step after this Phase I study straight to pivotal? Do you have a sense yet of what that looks like?

Samit，我想知道您能否告訴我們今年您預計將有多少 SLE 患者接受 NEX-T CAR-T 計劃治療？第一階段研究之後的下一步是關鍵嗎？你知道那是什麼樣子嗎？

Yes. Thank you for the question, Matt. Look, we are in the dose escalation phase. As you can recall, we have to go through one patient by one patient in the beginning. But very soon, we'll be able to treat a number of patients at the same time. I can't give you a number in terms of how many patients we intend to treat at this time, but certainly, the trials will remain open as we want to certainly get a good understanding of the efficacy and safety profile at the right dose for patients with SLE who have advanced disease.

是的。謝謝你的提問，馬特。看，我們正處於劑量遞增階段。正如您所記得的，我們一開始必須逐一檢查患者。但很快，我們將能夠同時治療多名患者。我無法告訴您我們目前打算治療多少患者的數字，但可以肯定的是，試驗將保持開放，因為我們希望充分了解正確劑量下的療效和安全性。患有晚期疾病的 SLE 患者。

We do intend to present the data later this year, emerging from the first trial. In terms of what the next steps would be, we will be engaging with some data in hand with the regulatory agencies in terms of defining what the trial should look like. In this particular case, with a single-arm open-label study such as been done with hematological malignancies, will that be the acceptable approach? Or will the regulators require a randomized approach? Those are yet to come. But certainly, looking forward to the emergency of this data and presenting that later in the year.

我們確實打算在今年稍後公佈第一次試驗的數據。至於接下來的步驟，我們將與監管機構合作，利用現有的一些數據來定義試驗的形式。在這種特殊情況下，透過單臂開放標籤研究（例如針對血液惡性腫瘤進行的研究），這會是可接受的方法嗎？或者監管機構會要求採取隨機方法嗎？這些還沒到來。但當然，我們期待這些數據的緊急出現並在今年稍後公佈。

The next question comes from Steve Scala of TD Cowen.

下一個問題來自 TD Cowen 的 Steve Scala。

I believe Milvexian's AFib trial right around now is at the point where Bayer stopped its Factor XI AFib trial. Can you reassure us that events in the Milvexian AFib trial are progressing as expected? And Samit, based on everything you know, are you very confident in Milvexian and AFib. The trial has been underway for approaching a year, so I would imagine some sort of look has already been taken.

我相信 Milvexian 的 AFib 試驗現在正是拜耳停止其 XI AFib 試驗的時候。您能否向我們保證 Milvexian AFib 試驗的進展符合預期？ Samit，根據你所知道的一切，你對 Milvexian 和 AFib 非常有信心嗎？該試驗已經進行了近一年，所以我想已經進行了某種調查。

Samit?

薩米特？

Thank you, Steve, for the question. Very thoughtful, as always. What we can tell you is the trial is continuously progressing. On all 3 trials, AF secondary stroke prevention and ACS, enrollment is going very well. And certainly, the DMC continues to oversee the trials, and we do not have any indication from the DMC otherwise.

謝謝你，史蒂夫，提出這個問題。非常周到，一如既往。我們可以告訴你的是，審判正在不斷取得進展。在所有 3 項試驗（AF 二級中風預防和 ACS）中，入組進展順利。當然，DMC 會繼續監督試驗，我們沒有從 DMC 得到任何其他指示。

We will continue to look at the data from a perspective of safety as well as the DMC will continue to look at the data. There's nothing more to report at this time. I would say one thing, though, that assuming just because a competitor trial failed for whatever reasons and the doses that they picked, we don't have that same philosophy. We actually did conduct 2 very well-designed studies. We picked differential doses between atrial fibrillation versus SSP and ACS, and those are the reasons to believe, and we will certainly be looking forward to the readout of these trials in '26 and '27.

我們將繼續從安全角度審視這些數據，DMC 也將繼續審視這些數據。目前沒有什麼好報告的。不過，我想說一件事，假設僅僅因為競爭對手的試驗因某種原因以及他們選擇的劑量而失敗，我們就沒有同樣的理念。事實上，我們確實進行了兩項精心設計的研究。我們在心房顫動與 SSP 和 ACS 之間選擇了不同的劑量，這些都是我們相信的理由，我們當然會期待在 26 年和 27 年公佈這些試驗的結果。

The next question comes from Terence Flynn of Morgan Stanley.

下一個問題來自摩根士丹利的特倫斯·弗林。

I was just wondering if you could elaborate on your thoughts on Breyanzi commercial potential this year, particularly in the second-line setting and how the final OS data might impact that? And then anything you're seeing with respect to outpatient treatment for Breyanzi here?

我只是想知道您是否可以詳細闡述您對 Breyanzi 今年商業潛力的看法，特別是在二線環境中，以及最終的作業系統資料可能會如何影響這一點？那麼您對 Breyanzi 的門診治療有什麼看法嗎？

Adam and Samit?

亞當和薩米特？

Yes, certainly. Thank you. So I'll start off and then pass it on. R&D comes first before commercial. So I'll start off with Breyanzi. Certainly looking forward to these 3 PDUFA dates that Adam had mentioned earlier as well as David in his remarks for follicular lymphoma, mantle cell lymphoma and CLL. And then, of course, we are planning to do few more trials in these lymphoma patients because that remains a very high unmet medical need.

是的，當然了。謝謝。所以我會開始，然後傳遞它。研發先於商業。我將從 Breyanzi 開始。當然期待 Adam 之前提到的這 3 個 PDUFA 日期，以及 David 在他關於濾泡性淋巴瘤、套細胞淋巴瘤和 CLL 的評論中。當然，我們計劃在這些淋巴瘤患者中進行更多試驗，因為這仍然是一個非常高的未滿足的醫療需求。

And then, of course, there are multiple other cell therapy products that are in development. So we'll be talking more about that. From the out-of-spec or the continuation of those discussions, we continue to engage with the regulatory authorities and we'll update at a later date once we have an inkling in terms of where we are landing on that. Adam?

當然，還有多種其他細胞治療產品正在開發中。所以我們將更多地討論這一點。從不符合規範或繼續進行這些討論的情況來看，我們將繼續與監管機構合作，一旦我們了解了我們的進展情況，我們將在稍後進行更新。亞當？

Yes. Thanks for the question. So we're pleased with Breyanzi's performance in the quarter. We saw double-digit growth quarter-on-quarter. We also expect to continue to make good progress in Breyanzi in 2024, supported by strengthening of our vector supply. In fact, we will see supply materialize even further in Q2 and expand to support our new indications for Breyanzi starting with the planned CLL indication in March, where Breyanzi will be the first and only cell therapy agent to have this indication.

是的。謝謝你的提問。因此，我們對 Breyanzi 本季的表現感到滿意。我們看到季度環比兩位數的成長。我們也預計在加強載體供應的支持下，2024 年 Breyanzi 將繼續取得良好進展。事實上，我們將看到第二季度供應進一步實現，並擴大以支持我們的Breyanzi 新適應症，從3 月份計劃的CLL 適應症開始，Breyanzi 將成為第一個也是唯一一個具有該適應症的細胞治療藥物。

As Samit alluded to, we're making good progress in reducing turnaround time out of spec in drug product capacity. So now as we move through the course of the first half of the year, with this brought label and LBCL, and now with 3 FDA priority reviews in the first half of the year, Breyanzi has the potential to treat the broadest array of B-cell malignancies of any CAR-T. And these indications we believe will double the addressable patient population for Breyanzi. So we're very pleased with what we're seeing and the progress that we're making. We are seeing increases in outpatient use because of the best-in-class safety profile that Breyanzi brings, and we expect strong demand growth this year.

正如薩米特所提到的，我們在減少藥品產能超出規格的周轉時間方面取得了良好進展。因此，現在隨著我們經歷上半年的過程，隨著標籤和 LBCL 的推出，現在上半年 FDA 的 3 項優先審查，Breyanzi 有潛力治療最廣泛的 B-任何 CAR-T 的細胞惡性腫瘤。我們相信這些適應症將使 Breyanzi 的可治療患者人數增加一倍。因此，我們對所看到的情況和所取得的進展感到非常滿意。由於 Breyanzi 帶來了一流的安全性，我們看到門診使用量增加，我們預計今年的需求將強勁成長。

The next question comes from Evan Seigerman of BMO Capital Markets.

下一個問題來自 BMO 資本市場的 Evan Seigerman。

So last week, you presented initial data from your antigen receptor ligand direct integrator at ASCO GU, then hosted an event for the cell side. I'd love for you to speak to why you think it's important for investors and analysts to pay attention to a Phase 1 asset at a company as large as Bristol-Myers? I know you have a lot going on in your pipeline. So why should we be focused on things like this?

上週，您在 ASCO GU 展示了抗原受體配體直接積分器的初始數據，然後為細胞方舉辦了一場活動。我希望您能談談為什麼您認為投資者和分析師關注像百時美施貴寶這樣大的公司的第一階段資產很重要？我知道您的管道中有很多事情要做。那我們為什麼要關注這樣的事情呢？

Samit, we'll start and then we'll turn it to Adam to get some feedback from KOLs on this product.

Samit，我們將開始，然後將其交給 Adam，以獲取 KOL 對該產品的一些反饋。

Thank you, Evan. I think it's a good question. And the reason we believe that it is important for us to be able to highlight this are multifold. Let me start off by saying, remember last year at the R&D Day, we had said that there are 2 platforms that are very critical and we believe in, and we are continuing to progress on them. AR-LDD, the molecule is the first protein degrader from that platform that goes into solid tumors, and we wanted to absolutely be able to demonstrate that it is as we anticipated it progressing well showing efficacy and manageable safety profile in patients with late-line prostate cancer.

謝謝你，埃文。我認為這是一個好問題。我們認為能夠強調這一點對我們來說很重要，原因是多方面的。首先我要說的是，記得去年在研發日，我們說過有兩個非常關鍵的平台，我們相信，我們正在繼續在它們上取得進展。 AR-LDD，該分子是該平台第一個進入實體瘤的蛋白質降解劑，我們希望絕對能夠證明它正如我們預期的那樣，在晚期患者中進展良好，顯示出療效和可控的安全性前列腺癌。

As you saw from the data, the PSA30, PSA50 reductions, the durability of that and those are truly correlated if you look at the data as well as in literature, the correlation of that impacting the overall survival. So we are truly excited about what we've seen thus far. We are, of course, enrolling more patients. We are in the dose optimization phase. We've had interactions with regulatory authorities and now planning for initiating the next phase of development registration trials within the next 6 to 12 months. Let me just pass it over to Adam to comment further from his perspective as well.

正如您從數據中看到的，如果您查看數據和文獻，PSA30、PSA50 的降低、其持久性和這些確實是相關的，它們影響整體生存率的相關性。因此，我們對迄今為止所看到的一切感到非常興奮。當然，我們正在招募更多患者。我們正處於劑量優化階段。我們已與監管機構進行了互動，目前計劃在未來 6 至 12 個月內啟動下一階段的開發註冊試驗。讓我將其轉交給 Adam，以便從他的角度進一步發表評論。

Yes. Thanks, Samit. Evan, thanks for the question. So we're excited about, as Samit said, the platform of protein degradation. And as it relates to AR-LDD, in prostate cancer, this diversifies our IO portfolio even further to complement some of the recent deals.

是的。謝謝，薩米特。埃文，謝謝你的提問。因此，正如薩米特所說，我們對蛋白質降解平台感到興奮。由於它與前列腺癌中的 AR-LDD 相關，這使我們的 IO 產品組合進一步多樣化，以補充最近的一些交易。

We had a number of KOL and community feedback coming out of the ASCO GU presentation and PLs have been enthusiastic about the profile, particularly around the efficacy of the asset, the durability of response. And when we ask community positions, they were reassured around the safety profile as well, stating that it was a manageable safety profile, and they were enthusiastic about moving this into Phase III registrational studies and look forward to have the opportunity to treat patients with late-line prostate cancer.

我們從 ASCO GU 演示中獲得了許多 KOL 和社區的反饋，並且 PL 對該簡介充滿熱情，特別是在資產的功效和響應的持久性方面。當我們詢問社區立場時，他們也對安全性感到放心，表示這是一個可控的安全性，他們熱衷於將其納入 III 期註冊研究，並期待有機會治療晚期患者線前列腺癌。

The next question comes from Carter Gould of Barclays.

下一個問題來自巴克萊銀行的卡特·古爾德。

For Adam, I wanted to come back to Camzyos. You sort of have shown a pretty steady kind of addition of sort of the same number of patients for each quarter. I would expect sort of now that you've gotten your feet under -- with the launch that, that number would be increasing sort of each quarter like we see with most launches, which I guess suggest there's some other sort of gating factor, whether that's logistics or whatnot. Can you maybe elaborate on what you're seeing and whether you disagree or agree with kind of how I frame that there? And to whatever extent you can comment on the trends going forward in '24?

對於 Adam，我想回到 Camzyos。您已經顯示出每個季度相同數量的患者數量相當穩定的增加。我預計現在你已經站穩了腳跟——隨著發布，這個數字每個季度都會增加，就像我們在大多數發布中看到的那樣，我想這表明還有其他一些限制因素，無論是那是物流或其他什麼的。您能否詳細說明您所看到的內容以及您是否同意或不同意我在那裡構建的方式？您能在多大程度上對 24 世紀的趨勢發表評論？

Adam?

亞當？

Sure, Carter. Thanks for the question. So we continue to make very good progress with Camzyos. As we talked about, we're investing further behind the brand in unbranded and branded direct-to-consumer. We do expect to see continued steady and consistent growth. As David mentioned in his opening remarks, we're averaging around 1,000 patients on a quarterly basis. Patient and physician feedback continue to be very positive. Remember, these patients are going to be on treatment for a very long time.

當然，卡特。謝謝你的提問。因此，我們繼續在 Camzyos 方面取得非常好的進展。正如我們所討論的，我們正在對非品牌和品牌直接面向消費者的品牌進行進一步投資。我們確實期望看到持續穩定和持續的成長。正如 David 在開場白中提到的，我們平均每季接待大約 1,000 名患者。患者和醫生的回饋仍然非常積極。請記住，這些患者將接受很長一段時間的治療。

And taking you back to JPMorgan. If you recall, Chris showed an analog where Camzyos is tracking into a very strong CV launch, in this case, ENTRESTO. So this is the way that cardiovascular launches uptake. And we are focused on continuing to drive breadth in our top COEs. We'll continue to expand outside of our top COEs and we're working to increase diagnosis rates by activating patients via our new DTC advertising. So that, coupled with new launches internationally, we are confident that this is going to lead to continued and sustained growth for this important brand.

帶你回到摩根大通。如果你還記得的話，Chris 展示了一個類比，Ca​​mzyos 正在追蹤一個非常強大的 CV 發布，在本例中為 ENTRESTO。這就是心血管啟動攝取的方式。我們致力於繼續擴大我們頂級 COE 的廣度。我們將繼續在頂級 COE 之外進行擴張，並致力於透過新的 DTC 廣告啟動患者來提高診斷率。因此，加上在國際上推出新產品，我們相信這將導致這個重要品牌的持續成長。

The next question comes from Mohit Bansal of Wells Fargo.

下一個問題來自富國銀行的莫希特·班薩爾。

This is Serena on for Mohit Bansal. So I wanted to ask about the Phase II Opdualag readout coming out early this year in first-line lung cancer. I was wondering how meaningful you think this data could be considering that the comparator arm is Opdivo chemo versus Opdivo Yervoy being the approved regimen?

我是小威 (Serena)，替莫希特·班薩爾 (Mohit Bansal) 發言。所以我想詢問今年年初推出的用於一線肺癌的 II 期 Opdualag 讀數。我想知道考慮到比較組是 Opdivo 化療，而 Opdivo Yervoy 是核准的治療方案，您認為這些數據有多有意義？

Samit?

薩米特？

Thank you for the question. Obviously, we're looking forward to seeing the data for Opdualag, a randomized Phase II study looking at the combination of Opdivo relatlimab plus chemotherapy comparing to Opdivo chemo. The intent of doing this is twofold. One, we wanted to get the contribution of component question out right away so that we can show the contribution of relatlimab on top of Opdivo with chemotherapy.

感謝你的提問。顯然，我們期待看到 Opdualag 的數據，這是一項隨機 II 期研究，旨在比較 Opdivo relatlimab 加化療的組合與 Opdivo 化療的比較。這樣做的目的是雙重的。第一，我們希望立即弄清楚成分問題的貢獻，以便我們能夠展示 relatlimab 在 Opdivo 化療基礎上的貢獻。

And number two, we also wanted to plan this study so that we can -- when we do go to Phase III, the appropriate control arm that is most widely used right now is pembro chemo. And therefore, we are set for that, dependent, of course, on the data. So later this quarter and this year, you will be able to hear about the data. And then based on the data, we will be making decisions on where to go with this drug.

第二，我們也想規劃這項研究，以便我們能夠——當我們進入第三階段時，目前最廣泛使用的適當控制臂是 pembro 化療。因此，我們已經做好了準備，當然這取決於數據。因此，本季末和今年，您將能夠聽到有關數據。然後根據數據，我們將決定在哪裡使用這種藥物。

The next question comes from Robyn Karnauskas of Truist Securities.

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

This is (inaudible) for Robyn. I have a follow-up question on Camzyos. Just wondering if you can talk a little bit about how you think the recent data from a competitor might broadly impact the landscape in ACM. Obviously, the drug is not approved yet, but do you see these data improving awareness? And based on that, do you expect to see any sort of inflection points? And also, can you talk a little bit more about your efforts ex U.S. and if we should continue to see steady growth or any sort of inflection point based on the reimbursements that you expect?

這是（聽不清楚）給羅賓的。我有一個關於 Camzyos 的後續問題。只是想知道您是否可以談談您認為競爭對手的最新數據可能如何廣泛影響 ACM 的前景。顯然，該藥物尚未獲得批准，但您認為這些數據是否提高了人們的認識？基於此，您是否期望看到任何類型的拐點？另外，您能否多談談您在美國以外的努力，以及我們是否應該繼續看到穩定增長或基於您期望的報銷的任何拐點？

Samit and Adam?

薩米特和亞當？

Yes. Thank you for the questions. The way we would look at it is that the competitor data actually further strengthens our confidence in Camzyos. And within the Camzyos clinical trials, we now have 3 Phase III trials that are readout with amazing transformational data.

是的。謝謝你的提問。我們認為，競爭對手的數據實際上進一步增強了我們對 Camzyos 的信心。在 Camzyos 臨床試驗中，我們現在有 3 項 III 期試驗，這些試驗具有驚人的轉化數據。

You've seen the data for EXPLORER, you've seen the data from VALOR, and recently, we had the readout of a Phase III trial in Japan as well, which replicates the results that we've already seen for the first 2 trials. As Adam would tell you, we've treated now thousands of patients, and that data also continues to showcase the efficacy of the drug as well as maintains the safety of the drug. As you will see when the data are presented from the real-world setting at ACC, what the overall safety profile of the drug is. So in general, what I would say is profile of the drug is. So in general, what I would say is that Camzyos lives up to its promise of a transformational potential for the patients. And any patient who goes on the drug, usually doesn't want to come off because of the benefit that they are achieving. Adam?

您已經看到了 EXPLORER 的數據，您已經看到了 VALOR 的數據，最近，我們也公佈了日本的 III 期試驗，該試驗複製了我們在前 2 項試驗中已經看到的結果。正如 Adam 告訴您的那樣，我們現在已經治療了數千名患者，這些數據也繼續展示藥物的功效並保持藥物的安全性。當 ACC 的真實環境中提供資料時，您將會看到該藥物的整體安全性狀況如何。所以總的來說，我想說的是藥物的概況。所以總的來說，我想說的是 Camzyos 兌現了為患者帶來變革潛力的承諾。任何繼續服藥的患者通常都不想停藥，因為他們所獲得的益處。亞當？

Yes. Thanks for the question. So certainly, when we look at the top line data from (inaudible) is consistent with our internal expectations. We'll obviously need to see the data set. But ultimately, we don't see any clinically meaningful differences in the data. In fact, when we spoke to many TLs after those data were shared, they have stated that (inaudible) data appears similar and undifferentiated from Camzyos. They also, of course, want to see the broad data set. They also talked about the difference in pVO2 being not a clinically meaningful endpoint and likely those -- any differences are due to differences in patient populations across the 2 studies.

是的。謝謝你的提問。因此，當然，當我們查看（聽不清楚）的頂線數據時，它與我們的內部預期一致。顯然我們需要查看資料集。但最終，我們在數據中沒有看到任何有臨床意義的差異。事實上，當我們在共享這些資料後與許多 TL 交談時，他們表示（聽不清楚）資料與 Camzyos 相似且沒有區別。當然，他們也希望看到廣泛的數據集。他們也談到 pVO2 的差異並不是一個有臨床意義的終點，任何差異都可能是由於兩項研究中患者群體的差異所造成的。

Actually, we will certainly be prepared for (inaudible) when it comes to market with our leading cardiovascular organization. And we have maintained a consistent view that we will remain leaders in this space. I've also said though that important thing to keep in mind with this class is we do see that another competitor, it could be a net positive to help drive awareness for patients with symptomatic oHCM and increased diagnosis rates, which is also really important.

事實上，當我們領先的心血管組織進入市場時，我們肯定會做好準備（聽不清楚）。我們始終堅信，我們將繼續保持這一領域的領導者地位。我還說過，雖然在這個課程中要記住的重要一點是我們確實看到了另一個競爭對手，但它可能是一個淨積極因素，有助於提高對有症狀的oHCM 患者的認識並提高診斷率，這也非常重要。

Finally, as it relates to expansion outside of the U.S., we're just starting to see expansion outside of the U.S. We've launched in Germany. We'll prepare to launch in Japan, in China in midyear and a host of other markets. So we'll start to see those sales manifest in the back end of the year and into 2025.

最後，由於涉及美國以外的擴張，我們剛開始看到美國以外的擴張，我們已經在德國推出了。我們將準備在日本、年中在中國以及許多其他市場推出。因此，我們將在今年年底和 2025 年開始看到這些銷售額。

The next question comes from James Shin of Deutsche Bank.

下一個問題來自德意志銀行的詹姆斯辛（James Shin）。

Just wanted to circle back on Zeposia. Adam, I think you mentioned earlier or late last year, the access was still improving for UC. Is that access going to improve meaningfully this year? Or is it going to take a little bit more time, sort of like a similar situation to Sotyktu and psoriasis?

只是想回到 Zeposia。 Adam，我想你去年早些時候或年底提到過，UC 的訪問仍在改善。今年這種訪問會得到有意義的改善嗎？還是需要更多的時間，有點像 Sotyktu 和牛皮癬的情況？

Yes. Thanks for the question. So overall, we're seeing solid and continued quarterly and year-on-year growth. As David shared, we showed 66% growth versus prior year. I think Zeposia has been really a tale of 2 launches. MS performance amongst the oral competitors is solid. We expect continued share growth there. And we're growing in the face of a declining oral market in favor of B-cell agents.

是的。謝謝你的提問。總體而言，我們看到了穩健且持續的季度和同比增長。正如 David 分享的那樣，我們的成長率比去年提高了 66%。我認為 Zeposia 確實是一個兩次發布的故事。 MS 在口說比賽中的表現非常出色。我們預計該地區的份額將持續成長。面對不斷下滑的口服市場，我們正在不斷成長，而 B 細胞藥物則受到青睞。

We continue to have an opportunity for continued growth in UC, which, as you know, is a very competitive market. We're making progress as volume and share are increasing. We are focused on expanding the breadth of prescribers. We're continuing to position Zeposia earlier in lines of treatment. And the opportunity for additional indications like Crohn's disease, the data readout later this year will also add to the sales for Zeposia. So again, we do expect to see continued growth for Zeposia as patients continue to accumulate and physicians continue to gain experience with the product.

我們在 UC 領域繼續有持續成長的機會，正如您所知，這是一個競爭非常激烈的市場。隨著數量和份額的增加，我們正在取得進展。我們致力於擴大處方者的範圍。我們將繼續將 Zeposia 置於治療的早期位置。今年稍後公佈的克羅恩病等其他適應症的機會也將增加 Zeposia 的銷售額。因此，隨著患者的不斷累積和醫生不斷獲得該產品的經驗，我們確實期望看到 Zeposia 的持續成長。

Great. And maybe time for 1 or 2 more. Maybe we'll go to the next question for now and then 1 after that, Andrea.

偉大的。也許還有時間再做一兩個。安德里亞，也許我們現在會討論下一個問題，然後再討論下一個問題。

Okay. The next question is from Akash Tewari of Jefferies.

好的。下一個問題來自 Jefferies 的 Akash Tewari。

Can you comment on what drives your confidence on the Alzheimer's psychosis reading out positively? Any color on what percent of patients you think will be able to get on the high dose of KarXT? And what percent of dropouts do you think will occur in the treatment arms through these ADEPT trials? Should it be roughly similar to what we've seen in the schizophrenia studies?

您能評論一下是什麼讓您對阿茲海默症精神病產生正面的信心嗎？您認為有多少百分比的患者能夠接受高劑量的 KarXT？您認為透過這些 ADEPT 試驗，治療組的退出率是多少？它應該與我們在精神分裂症研究中看到的大致相似嗎？

Samit?

薩米特？

Thank you for the question, Akash. Look, our confidence in -- remains very high. And the reason for that is if you go back to the first publications of the xanomeline trial, that was a study that was published, I think, in 1997, in fact. And if you look at that data, there was a positive trial, which tells us that M1/M4 muscarinic receptor agonist do work over there. The obvious issue over there was the toxicity due to the peripheral muscarinic agonism that was seen. So that combination with trospium has led to obviously better outcomes as we saw in schizophrenia.

謝謝你的提問，阿卡什。看，我們對——的信心仍然非常高。原因是，如果你回顧 xanomeline 試驗的第一份出版物，我認為事實上這是一項於 1997 年發表的研究。如果你看一下這些數據，你會發現一項積極的試驗，它告訴我們 M1/M4 毒蕈鹼受體激動劑在那裡確實起作用。那裡明顯的問題是由於所觀察到的外周毒蕈鹼激動作用而產生的毒性。因此，與曲司溴銨聯合使用可以帶來明顯更好的結果，正如我們在精神分裂症中所看到的。

The trial in AD psychosis is right now at the beginning stages. So the doses are being tested right now. So it's hard to comment on what the dose utilization would be, where the patients will be on the highest doses, it's too early to tell. We'll have to get into it. But of course, Karuna and us, we continue to operate as separate companies right now. And once the transaction closes, then we'll be able to get deeper into it and look at what the future looks like. So we'll be talking about it at a later date.

AD 精神病的試驗目前正處於開始階段。所以現在正在測試劑量。因此，很難評論劑量利用率是多少，患者將在哪裡接受最高劑量，現在下結論還為時過早。我們必須深入其中。但當然，卡魯納和我們現在繼續作為獨立公司運作。一旦交易完成，我們就能夠更深入地了解它並展望未來。所以我們稍後再討論它。

Let's go to our last one, please, Andrea.

安德里亞，請讓我們看最後一篇。

The next question comes from Rajesh Kumar of HSBC.

下一個問題來自匯豐銀行的 Rajesh Kumar。

I appreciate that you can't obviously give any color on Eliquis price negotiations. But when we look at your margin guidance this year, I'm assuming that you have made an assumption and that is implicit in that guidance an outcome of this negotiation? Or should we expect, as we get more clarity to adjust your guidance from what you lost?

我理解你不能明顯地對 Eliquis 的價格談判給出任何顏色。但是，當我們查看您今年的保證金指導時，我假設您已經做出了一個假設，並且該假設隱含在該指導中是本次談判的結果？或者，當我們變得更加清晰時，我們是否應該期望根據您所失去的情況來調整您的指導？

So Rajesh, thanks for the question. I'll try to start and then I'll turn it over to David to just talk a little bit about how we're thinking about margins, right? We're not going to be able to give any additional discussion around where we sit with IRA on Eliquis. We got the initial offer. We're going to follow the process they have and the price will be public in September, and we won't be providing additional details around that. But maybe David can talk to you a bit about how we think about margins generally.

拉傑什，謝謝你的提問。我會嘗試開始，然後將其交給大衛，讓他談談我們如何考慮利潤率，對嗎？我們無法就 Eliquis 與 IRA 的立場進行任何額外的討論。我們得到了最初的報價。我們將遵循他們的流程，價格將於 9 月公開，我們不會提供更多細節。但也許大衛可以和你談談我們對利潤率的一般看法。

Just overall, as we guided, we anticipate gross margins to be about 74% this year, and that's really driven by the LOE brands coming down. But as the growth portfolio continues to increase, obviously, that will help offset longer term where those gross margins are going. We also said that our operating expenses grew in the mid low single-digit range. And with that, really, there's a lot going on there that as we said on Karuna, we're going to find savings and efficiencies in order to cover those expenses.

總體而言，正如我們所指導的那樣，我們預計今年的毛利率約為 74%，這實際上是由 LOE 品牌的下降所推動的。但顯然，隨著成長投資組合的持續增加，這將有助於抵消這些毛利率的長期走勢。我們也表示，我們的營運費用成長在中低個位數範圍內。事實上，正如我們在卡魯納所說，我們將找到節省和提高效率的方法來支付這些費用。

But also, as Adam indicated, and I said in my opening remarks, we're increasing our investments in Camzyos and Sotyktu. So with that, we're finding from our legacy brands, re-funneling those resources into that. And all of that said, we'll be able to deliver a margin greater than 37% for the year, which we feel very confident about.

而且，正如 Adam 所指出的，以及我在開場白中所說的，我們正在增加對 Camzyos 和 Sotyktu 的投資。因此，我們從我們的傳統品牌中尋找資源，將這些資源重新投入其中。綜上所述，我們今年的利潤率將超過 37%，對此我們非常有信心。

Thanks, David. So I think that was it for the time that we have, but I thank you all for joining on the call today. I know it's a very busy day for all of you. Hopefully, you get a sense from the discussion this morning that we exited 2023 with good momentum to capitalize on the strategy that we have articulated about how we're going to navigate this decade. And of course, we look forward to sharing the progress against that on future calls.

謝謝，大衛。我想我們的時間就到此為止，但我感謝大家參加今天的電話會議。我知道這對你們所有人來說都是非常忙碌的一天。希望您能從今天早上的討論中了解到，我們以良好的勢頭結束了 2023 年，以利用我們闡明的關於如何度過這十年的戰略。當然，我們期待在未來的電話會議上分享相關進展。

And with that, we'll close the call. And as always, the team is available to answer any questions following today's discussion, and I hope all of you have a very good day and a good weekend. Thanks.

至此，我們就結束通話了。像往常一樣，團隊可以回答今天討論後的任何問題，我希望大家度過愉快的一天和愉快的周末。謝謝。

The conference has now concluded. Thank you for attending today's presentation, and you may now disconnect.

會議現已結束。感謝您參加今天的演示，您現在可以斷開連接了。