施貴寶 (BMY) 2024 Q3 法說會逐字稿

Good day, and welcome to the Bristol-Myers Squibb third-quarter 2024 earnings conference call. (Operator Instructions) Please note this event is being recorded.

美好的一天，歡迎參加百時美施貴寶 2024 年第三季財報電話會議。 （操作員說明）請注意此事件正在被記錄。

I would now like to turn the conference over to Mr. Chuck Triano, Senior Vice President of Investor Relations. Please go ahead, sir.

現在我想將會議交給投資者關係高級副總裁 Chuck Triano 先生主持。請繼續，先生。

Thank you, and good morning, everyone. I'm happy to be here at Bristol-Myers Squibb, and we appreciate you joining our third-quarter 2024 earnings call.

謝謝大家，大家早安。我很高興來到百時美施貴寶，感謝您參加我們的 2024 年第三季財報電話會議。

Joining me this morning with prepared remarks are Chris Boerner, our Board Chair and 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.

今天早上與我一起發表準備好的演講的是我們的董事會主席兼首席執行官 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。

Earlier this morning, we posted our quarterly slide presentation to bms.com that you can use to follow along with Chris and David's remarks. Before we get started, I'll remind everybody that during this call, we will make statements about the company's future plans and prospects that constitute forward-looking statements.

今天早些時候，我們在 bms.com 上發布了季度幻燈片演示文稿，您可以使用它來了解 Chris 和 David 的言論。在開始之前，我要提醒大家，在這次電話會議中，我們將就公司的未來計畫和前景發表前瞻性聲明。

Actual results may differ materially from those indicated by those 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. And we specifically disclaim any obligation to update forward-looking statements even if our estimates change.

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。

Thank you, Chuck, and thank you, all, for joining us this morning. Starting on slide 4. Our third-quarter results reflect our continued focus on near-term execution and building the foundation for long-term sustainable growth. During the quarter, we saw solid demand for key products across our growth and legacy portfolios.

謝謝查克，也謝謝大家今天早上加入我們。從投影片 4 開始。在本季度，我們看到對我們的成長和傳統產品組合中的關鍵產品的強勁需求。

We remained disciplined in managing expenses, and we continue to advance important pipeline programs. Let me highlight a few achievements in the quarter. Growth portfolio revenues increased 20% in Q3 at constant currency and now account for approximately half of total revenues. These are primarily young assets that have exclusivity well into the next decade.

我們在管理開支方面保持嚴格，並繼續推動重要的管道專案。讓我重點介紹本季的一些成就。以固定匯率計算，第三季成長投資組合收入成長了 20%，目前約佔總營收的一半。這些主要是年輕資產，在未來十年內仍具有排他性。

Our legacy portfolio also performed well, generating cash flow that allows us to strategically invest in growth opportunities. During the quarter, we achieved several clinical and regulatory milestones. Notably, we reestablished our presence in neuroscience with the approval of COBENFY, which I'll speak to in a moment.

我們的傳統投資組合也表現良好，產生的現金流使我們能夠對成長機會進行策略性投資。在本季度，我們實現了多個臨床和監管里程碑。值得注意的是，我們在 COBENFY 的批准下重新確立了我們在神經科學領域的地位，我稍後會談到這一點。

We also strengthened our leading oncology portfolio. And earlier this month, we received FDA approval for an OPDIVO-based perioperative treatment regimen in non-small cell lung cancer. Additionally, we continue to advance our innovative pipeline. In oncology, we presented data at ESMO, highlighting eight new registrational opportunities.

我們也加強了領先的腫瘤學產品組合。本月早些時候，我們獲得 FDA 批准基於 OPDIVO 的非小細胞肺癌圍手術期治療方案。此外，我們繼續推進我們的創新管道。在腫瘤學方面，我們在 ESMO 上展示了數據，並重點介紹了八個新的註冊機會。

We shared positive clinical data for our nivolumab plus relatlimab high-dose combination in first-line lung cancer, which is now advancing to Phase 3. And we talked about the progress we're making across other promising assets and modalities, including our bispecific ADC and our radiopharmaceutical pipeline. This past week, at ENA, we also presented promising Phase 1 data for our PRMT5 program across all the tumors.

我們分享了我們的nivolumab 加relatlimab 高劑量組合治療一線肺癌的積極臨床數據，該組合現已進入3 期。性愛ADC以及我們的放射性藥物管路。上週，在 ENA 上，我們也展示了 PRMT5 計畫針對所有腫瘤的有前景的 1 期數據。

Turning to slide 5. The acquisition of Karuna Therapeutics is a key example of how we are strengthening our long-term growth outlook. We're proud to highlight the recent FDA approval of COBENFY, formerly known as KarXT with a strong label that reflects its efficacy and safety profile.

轉向投影片 5。我們很自豪地強調 COBENFY（以前稱為 KarXT）最近獲得 FDA 批准，其強大的標籤反映了其功效和安全性。

This milestone marks significant progress in delivering value from the Karuna acquisition for patients. COBENFY is the first truly novel mechanism approved for adults with schizophrenia in decades, and it addresses one of the most significant unmet needs in mental health. There are approximately 1.6 million people being for schizophrenia in the US alone, many of whom have endured debilitating side effects from older treatments.

這一里程碑標誌著收購 Karuna 為患者帶來價值方面取得了重大進展。 COBENFY 是幾十年來第一個被批准用於成人精神分裂症患者的真正新穎的機制，它解決了心理健康領域最重要的未滿足需求之一。光是在美國就有大約 160 萬人患有精神分裂症，其中許多人忍受著舊療法帶來的令人衰弱的副作用。

COBENFY delivers compelling efficacy without the notable side effects associated with atypicals. The BMS team has been laying the groundwork for a successful launch. We built an experienced sales and medical team engaged with payers to secure access and develop sophisticated patient support services. We have ongoing clinical programs in adjunctive schizophrenia with Phase 3 data expected in 2025.

COBENFY 具有令人信服的功效，且沒有與非典型藥物相關的顯著副作用。 BMS 團隊一直在為成功發布奠定基礎。我們建立了一支經驗豐富的銷售和醫療團隊，與付款人合作，以確保獲得服務並開發複雜的患者支援服務。我們正在進行輔助精神分裂症的臨床項目，預計 2025 年將獲得第 3 期數據。

And we have expanded the ongoing ADEPT program in Alzheimer's disease psychosis with Phase 3 data expected in 2026. We remain on track to start registrational trials next year in Alzheimer's agitation, Alzheimer's cognition, bipolar disorder and autism spectrum disorder. Adam and Samit can speak more to our launch progress in schizophrenia and other potential indications, we are actively assessing for COBENFY in Q&A.

我們也擴大了正在進行的阿茲海默症精神病ADEPT 項目，預計將於2026 年獲得3 期數據。相情感障礙和自閉症譜系障礙的註冊試驗。 Adam 和 Samit 可以更多地談論我們在精神分裂症和其他潛在適應症方面的上市進展，我們正在問答中積極評估 COBENFY。

Turning to slide 6. I'll spend a moment updating you on our progress against our key strategic priorities. First, we're focused on transformational medicines where we have a competitive advantage. We are advancing our mission to serve patients with first or best-in-class treatments across our therapeutic areas. This includes driving leadership in hematology, cardiology and oncology therapeutic areas with products like Reblozyl, Breyanzi, CAMZYOS and Opdualag.

轉向投影片 6。首先，我們專注於我們擁有競爭優勢的轉化藥物。我們正在推進我們的使命，在我們的治療領域為患者提供一流或一流的治療。這包括透過 Reblozyl、Breyanzi、CAMZYOS 和 Opdualag 等產品推動血液學、心臟病學和腫瘤學治療領域的領導地位。

At the same time, we're strengthening our innovative pipeline by prioritizing key programs. One asset that continues to advance well as milvexian. We continue to see considerable unmet need across indications, in particular, AF as well as a large commercial opportunity. Today, we want to share an encouraging update related to our atrial fibrillation Phase 3 trial, which continues to recruit very well. As you'll soon see on clinicaltrials.gov we and our partner, J&J, have approved an increase in patient enrollment side.

同時，我們正在透過優先考慮關鍵項目來加強我們的創新管道。一項與米爾維西安一樣繼續良好發展的資產。我們繼續看到各種適應症的大量未滿足需求，特別是心房顫動，以及巨大的商業機會。今天，我們想分享一個與心房顫動第 3 期試驗相關的令人鼓舞的最新消息，該試驗的招募情況繼續良好。正如您很快就會在 ClinicalTrials.gov 上看到的那樣，我們和我們的合作夥伴強生 (J&J) 已批准增加患者入組人數。

This is because at this time, based on review of event rates, we are seeing a lower rate of strokes and systemic embolism than originally anticipated, and the increased enrollment supports maintaining the planned data readout in 2027.

這是因為，目前，根據對事件發生率的審查，我們發現中風和全身性栓塞的發生率低於最初預期，並且入組人數的增加支持維持 2027 年計劃的數據讀出。

As a reminder, as described in our published study design paper, we indicated that the sample size may be adjusted based on review of event rates. We remain confident in the design and progress of the program. Beyond milvexian, we continue to advance other programs where we have a right to win. This includes our CD19 NEX-T cell therapy, our radiopharmaceutical and protein degradation platforms as well as additional indications for COBENFY.

提醒一下，正如我們發表的研究設計論文中所述，我們指出樣本大小可能會根據事件發生率的審查進行調整。我們對該計劃的設計和進展仍然充滿信心。除了 Milvexian 之外，我們還繼續推進其他我們有權獲勝的項目。這包括我們的 CD19 NEX-T 細胞療法、我們的放射性藥物和蛋白質降解平台以及 COBENFY 的其他適應症。

Our second priority is driving operational excellence. We are reviewing overall spending and prioritizing investments that will deliver the best long-term returns. We remain on track to deliver $1.5 billion in savings by the end of 2025. And -- these savings will be reinvested into high ROI opportunities that serve patients' needs and accelerate growth.

我們的第二要務是推動卓越營運。我們正在審查整體支出並優先考慮能夠帶來最佳長期回報的投資。我們仍有望在 2025 年底之前節省 15 億美元。

We are becoming a more agile company with stronger commercial and pipeline execution. Our progress on this front was demonstrated by the performance of our growth portfolio in Q3, the approval of COBENFY and acceleration of key programs. We see the drive for greater operational excellence as a continuous process. As such, -- we're exploring opportunities to further improve productivity and efficiency over the coming quarters. Our third priority is to strategically allocate capital for long-term growth and returns.

我們正在成為一家更敏捷的公司，具有更強的商業和管道執行力。我們在這方面取得的進展體現在我們第三季成長投資組合的表現、COBENFY 的批准和關鍵項目的加速。我們將追求卓越營運視為一個持續的過程。因此，我們正在探索在未來幾季進一步提高生產力和效率的機會。我們的第三個優先事項是策略性地配置資本以實現長期成長和回報。

We remain focused on our near-term goal of de-levering our balance sheet. We made further progress during Q3 and are on track to pay down our target of $10 billion of debt by the first half of 2026. We're committed to the dividend, and we will continue to invest strategically in growth through our own pipeline as well as sourcing innovation externally.

我們仍然專注於去槓桿化資產負債表的近期目標。我們在第三季度取得了進一步進展，並預計在 2026 年上半年償還 100 億美元債務的目標。

Now turning to upcoming milestones on slide 7. At the American College of Rheumatology's annual meeting in November, we will present promising Phase 1 data for our CD19 NEX-T cell therapy. This is a next-generation immunology asset, leveraging the Breyanzi construct.

現在轉向幻燈片 7 上即將到來的里程碑。這是利用 Breyanzi 構造的下一代免疫學資產。

We are optimistic about its potential to deliver benefits for patients across multiple immunology indications by resetting the immune system. In late December, we expect the FDA's decision on the subcutaneous formulation of nivolumab. We anticipate this launch in early 2025 will provide an important benefit for both patients and physicians while extending our leadership in immuno-oncology into the next decade.

我們對其透過重置免疫系統為多種免疫學適應症患者帶來益處的潛力持樂觀態度。 12 月底，我們預計 FDA 將就納武單抗皮下製劑做出決定。我們預計 2025 年初的這項推出將為患者和醫生帶來重要的好處，同時將我們在免疫腫瘤學領域的領先地位延續到下一個十年。

We're also on track to share top line Phase 3 data from SOTYKTU in psoriatic arthritis by year-end. This data should help strengthen the competitive profile for SOTYKTU as roughly one-third of psoriasis patients also have psoriatic arthritis.

我們也有望在年底前分享 SOTYKTU 治療乾癬性關節炎的 3 期主要數據。這些數據應有助於增強 SOTYKTU 的競爭優勢，因為大約三分之一的乾癬患者也患有乾癬性關節炎。

Turning to our outlook on slide 8. Given the strength of our results year-to-date, we are raising both our full year revenue target and our full year EPS guidance. David will discuss these updates in more detail shortly. Looking ahead, I'm confident in our ability to deliver long-term value for patients and our shareholders.

轉向幻燈片 8 中的展望。大衛將很快更詳細地討論這些更新。展望未來，我對我們為患者和股東創造長期價值的能力充滿信心。

To summarize on slide 9, I'm pleased with our achievements in critical areas. Our overall business mix is beginning to transform as our growth portfolio is becoming a bigger component. The US approval of COBENFY adds another asset with multibillion-dollar potential to serve more patients and accelerate growth.

總結投影片 9，我對我們在關鍵領域的成就感到滿意。隨著我們的成長投資組合成為更大的組成部分，我們的整體業務組合正在開始轉變。 COBENFY 在美國的批准增加了另一項具有數十億美元潛力的資產，可以服務更多患者並加速成長。

Our pipeline continues to advance with additional near-term catalysts and we are maintaining a disciplined focus on expense management, driving initiatives across the company to lower cost. These actions underscore our focus on executing in the near term while laying the groundwork for long-term sustainable growth. We look forward to keeping you updated as we build momentum with important milestones in 2025 and significant data flow in 2026.

我們的產品線在其他近期催化劑的推動下繼續推進，我們一直嚴格關注費用管理，推動整個公司採取降低成本的措施。這些行動強調了我們注重短期執行，同時為長期永續成長奠定基礎。我們期待為您提供最新動態，因為我們將在 2025 年實現重要里程碑，並在 2026 年實現重要資料流，從而打造動力。

Before I close, I want to thank our employees for their dedication and performance in the quarter. Together, we are building a strong future for BMS and the patients we serve. Now I'll turn it over to David.

在結束之前，我要感謝我們的員工在本季度的奉獻和表現。我們正在共同為 BMS 和我們服務的患者創造一個美好的未來。現在我把它交給大衛。

Thank you, Chris, and good morning, everyone. I'm pleased to share our quarterly financial performance. As a reminder, unless otherwise stated, all comparisons are made from the same period in 2023 and sales growth rates will be discussed on an underlying basis which excludes the impact of foreign exchange, all references to our P&L on a non-GAAP basis.

謝謝克里斯，大家早安。我很高興分享我們的季度財務表現。提醒一下，除非另有說明，所有比較均來自 2023 年同期，銷售成長率將在排除外匯影響的基本基礎上進行討論，所有參考均基於非公認會計準則 (Non-GAAP) 基礎上的損益表。

Let's start on slide 10 with some highlights from our third quarter sales. we demonstrated solid commercial performance in the third quarter with higher sales driven primarily by our growth brands. The growth portfolio delivered another quarter of double-digit growth, up 20% with continued progress across key brands, including Reblozyl, Breyanzi.

讓我們從幻燈片 10 開始，介紹我們第三季銷售的一些亮點。我們在第三季展現了穩健的商業業績，主要由我們的成長品牌推動銷售額增加。隨著 Reblozyl、Breyanzi 等主要品牌的持續進步，成長型產品組合又實現了四分之一的兩位數成長，增幅達 20%。

And our legacy portfolio also performed well with US growth led by Eliquis, partially offset by lower sales of Sprycel. As a reminder, the LOE for Sprycel in the US recently occurred on September 1, and the LOE for POMALYST in Europe happened back in August.

我們的傳統產品組合在 Eliquis 引領的美國成長中也表現良好，但部分被 Sprycel 銷售下降所抵消。提醒一下，美國 Sprycel 的 LOE 最近發生在 9 月 1 日，歐洲 POMALYST 的 LOE 發生在 8 月。

Our continued focus on commercial execution enabled us to deliver nearly half of our sales in the third quarter from the growth portfolio. And with the recent US approval and launch of COBENFY, our sales mix will continue to diversify and provide a stronger foundation for growth. Importantly, we will continue to optimize the strong cash flow generated from the legacy portfolio to invest in growth opportunities.

我們對商業執行的持續關注使我們能夠在第三季度實現近一半的銷售額來自成長產品組合。隨著 COBENFY 最近在美國獲得批准和上市，我們的銷售組合將繼續多元化，並為成長提供更堅實的基礎。重要的是，我們將繼續優化遺留投資組合產生的強勁現金流，以投資成長機會。

Before going into key brand performance, it's important to note that third quarter sales were impacted by the reversal of an approximate $150 million inventory build from the second quarter. This tempered growth across several brands, primarily OPDIVO, and as well as Opdualag, CAMZYOS and some immunology products.

在討論關鍵品牌業績之前，需要注意的是，第三季的銷售額受到第二季約 1.5 億美元庫存建設逆轉的影響。這抑制了多個品牌的成長，主要是 OPDIVO，以及 Opdualag、CAMZYOS 和一些免疫學產品。

Let's start with our oncology business on slide 11. Global sales of OPDIVO were higher in the third quarter, reflecting solid demand growth outside the US Looking ahead, we continue to expect global full year sales growth to be in the mid-single-digit range. We remain focused on the anticipated approval and launch of the subcutaneous formulation of nivolumab which, as Chris mentioned, is expected to receive FDA approval by year-end.

讓我們從幻燈片11 上的腫瘤業務開始。範圍內。我們仍然關注納武單抗皮下製劑的預期批准和上市，正如克里斯所提到的，預計該製劑將在年底獲得 FDA 批准。

With this anticipated approval, we will have the potential to extend the durability of our immuno-oncology portfolio into the next decade. Moving to Optolag, we delivered strong double-digit growth in the third quarter, driven primarily by demand. three years post launch, Opdualag has become a standard of care in first-line melanoma in the US with 30% market share.

憑藉這一預期的批准，我們將有可能將我們的免疫腫瘤產品組合的耐用性延長到下一個十年。轉向 Optolag，我們在第三季實現了兩位數的強勁成長，這主要是由需求推動的。推出三年後，Opdualag 已成為美國一線黑色素瘤的治療標準，佔 30% 的市佔率。

Outside the US, third quarter sales benefited from the strong uptake in newly launched markets such as the UK, Brazil and Australia. Moving to our cardiovascular portfolio on slide 12. Eliquis is the leading anticoagulant worldwide and delivered double-digit sales growth in the third quarter. US sales benefited from the higher demand and market share gains.

在美國以外，第三季的銷售額受惠於英國、巴西和澳洲等新推出市場的強勁成長。在投影片 12 上前往我們的心血管產品組合。美國的銷售受益於更高的需求和市場份額的成長。

Sequentially, as we've seen historically, US sales included an unfavorable gross to net impact related to the Medicare coverage gap. Outside the US, sequential sales of Eliquis reflected higher demand across key markets and favorable inventory compared to the prior quarter.

因此，正如我們從歷史上看到的那樣，美國的銷售額包括與醫療保險覆蓋範圍缺口相關的不利的總淨影響。在美國以外，Eliquis 的連續銷售反映了與上一季相比主要市場的需求增加和庫存有利。

Turning to CAMZYOS. Third quarter sales more than doubled, driven by strong US demand for new patient starts and an increasing number of patients on commercial drug. During the third quarter, we saw steady patient adoption with nearly 20% growth in patients on commercial drug, more than doubling the number from a year ago.

轉向 CAMZYOS。由於美國對新患者的強勁需求以及使用商業藥物的患者數量不斷增加，第三季銷售額增加了一倍多。第三季度，我們看到患者的採用率穩定，使用商業藥物的患者數量增加了近 20%，比一年前增加了一倍多。

Outside the US, sequential sales growth reflected higher demand in newly launched markets in Europe. Now let's turn to hematology on slide 13. Sales of Reblozyl grew 81% in the third quarter, with strong double-digit growth, both in the US and international markets. The US sales were driven by continued demand in first-line setting, outside the US, recent first-line reimbursement in Europe and Japan contributed to the strong performance in the quarter.

在美國以外的地區，銷售額的環比成長反映了歐洲新推出市場的需求增加。現在讓我們轉向幻燈片 13 上的血液學。美國的銷售受到一線環境持續需求的推動，在美國以外，歐洲和日本最近的一線報銷也為本季的強勁表現做出了貢獻。

In cell therapy, sales of Breyanzi more than doubled versus prior year, driven by demand in new indications and improved manufacturing capacity and reliability. In the US, sales grew more 40% on a sequential basis driven primarily by pent-up demand in two of our newly approved indications, follicular lymphoma and mantle cell lymphoma. We expect more modest sequential growth from third quarter to fourth quarter as demand normalizes.

在細胞治療領域，受新適應症需求以及生產能力和可靠性提高的推動，Breyanzi 的銷售額比去年增長了一倍多。在美國，銷售額環比增長了 40% 以上，這主要是由於我們新批准的兩個適應症（濾泡性淋巴瘤和套細胞淋巴瘤）被壓抑的需求所推動的。隨著需求正常化，我們預計第三季到第四季的環比成長將更為溫和。

Also in cell therapy, despite a competitive market, bema performed well in the third quarter with solid demand growth in both the US and international markets. Now moving to immunology on slide 14. Sales SOTYKTU nearly doubled when compared to the impact of the $30 million clinical trial purchase in the third quarter of last year.

同樣在細胞治療領域，儘管市場競爭激烈，但 bema 在第三季表現良好，美國和國際市場的需求成長強勁。現在轉向幻燈片 14 上的免疫學。

Outside the US, sales grew year-over-year, benefiting from the launch in a number of international markets. Looking to the fourth quarter, we expect a step-up in gross to net discounts resulting from increased rebating associated with our approved access position. This would result in the fourth quarter sales being similar to this quarter.

在美國以外的地區，得益於在多個國際市場的推出，銷售額逐年成長。展望第四季度，我們預計由於與我們批准的准入位置相關的回扣增加，總折扣與淨折扣將增加。這將導致第四季度的銷售額與本季相似。

As we said previously, we expect that over time, demand growth will offset these pressures. Now turning to the P&L on slide 15. In addition to solid commercial execution, our third quarter performance demonstrated our focus on financial discipline and steady progress against our $1.5 billion cost savings program.

正如我們之前所說，我們預計隨著時間的推移，需求成長將抵消這些壓力。現在轉向幻燈片 15 上的損益表。

As a reminder, we initiated this program to offset incremental OpEx from the recent deals. Savings from across the organization include reductions in direct clinical trial expense, site rationalization, elimination of roles and a reduction in headcount. As we said previously, we expect the majority of the savings to come through this year. As we realize these savings, we are strategically reinvesting in high potential opportunities to fuel long-term growth and innovation in key areas.

提醒一下，我們啟動此計劃是為了抵消最近交易中增量營運支出。整個組織的節省包括直接臨床試驗費用的減少、場地合理化、角色的消除和員工人數的減少。正如我們之前所說，我們預計大部分節省將在今年實現。當我們實現這些節省後，我們正在策略性地對高潛力機會進行再投資，以推動關鍵領域的長期成長和創新。

Moving to gross margin. We saw a decline in the quarter of about 130 basis points, driven primarily by product mix. Operating expenses, excluding in-process R&D were impacted by higher deal-related spend, partially offset by savings from our efficiency initiatives.

轉向毛利率。我們看到本季下降了約 130 個基點，這主要是由產品組合推動的。營運支出（不包括正在進行的研發）受到交易相關支出增加的影響，但部分被我們效率措施節省的成本所抵銷。

Our effective tax rate in the quarter changed from 11.6% in the prior year to 18.5%, impacted by onetime adjustment in 2023 resulting from newly issued IRS guidance. Overall, third quarter earnings per share were $1.80. Now moving to the balance sheet and capital allocation highlights. We ended the quarter with approximately $8.4 billion in cash, cash equivalents and marketable debt securities on hand.

受新發布的國稅局指導方針導致的 2023 年一次性調整的影響，我們本季的有效稅率從上一年的 11.6% 變為 18.5%。總體而言，第三季每股收益為 1.80 美元。現在轉向資產負債表和資本配置重點。本季結束時，我們手頭上持有約 84 億美元的現金、現金等價物和可流通債務證券。

During the third quarter, both our growth and legacy portfolios delivered solid revenue growth, contributing to robust operating cash flow of approximately $5.6 billion. In terms of capital allocation, we remain focused on strengthening our balance sheet. We are executing our plan to pay down approximately $10 billion of debt. And relative to our position at the end of the first quarter, we have reduced it by $5.9 billion. This includes roughly $3 billion of commercial paper and 2.9% of long-term debt.

第三季度，我們的成長和傳統投資組合都實現了穩健的收入成長，帶來約 56 億美元的強勁營運現金流。在資本配置方面，我們仍專注於強化資產負債表。我們正在執行償還約 100 億美元債務的計劃。相對於第一季末的頭寸，我們減少了 59 億美元。其中包括約 30 億美元的商業票據和 2.9% 的長期債務。

As we previously have said, we remain committed to our dividend. Our strong cash flow profile enables us to address these priorities while also strengthening our outlook. Turning to 2024 non-GAAP guidance. As is our practice, we provide revenue guidance on a reported basis as well as on an underlying basis, which assumes currency remains consistent with prior year.

正如我們之前所說，我們仍然致力於派發股息。我們強大的現金流狀況使我們能夠解決這些優先事項，同時也增強了我們的前景。轉向 2024 年非 GAAP 指引。按照我們的慣例，我們在報告的基礎上以及基礎基礎上提供收入指引，假設貨幣與上一年保持一致。

We now expect full year 2024 revenue to increase approximately 5% as reported and approximately 6% at constant currency, primarily due to higher-than-anticipated sales of REVLIMID. We are pleased with the performance of both growth and legacy portfolios. And in legacy, we have updated our full year sales estimate of REVLIMID to approximately $5.5 billion.

我們目前預計 2024 年全年營收將按報告增長約 5%，按固定匯率計算約增長 6%，這主要是由於瑞復美 (REVLIMID) 的銷售額高於預期。我們對成長型投資組合和傳統投資組合的表現感到滿意。在傳統業務方面，我們已將 REVLIMID 的全年銷售額預估更新至約 55 億美元。

As a reminder, for modeling purposes, in addition to REVLIMID, other legacy brands should soften in the fourth quarter due to competition from generics for ABRAXANE in the US and POMALYST in Europe. Turning to gross margin. We now expect a slightly tighter range to reflect the impact of our US sales mix.

提醒一下，出於建模目的，除了 REVLIMID 之外，由於來自美國 ABRAXANE 和歐洲 POMALYST 仿製藥的競爭，其他傳統品牌在第四季度應該會軟化。轉向毛利率。我們現在預計範圍會稍微收緊，以反映我們美國銷售組合的影響。

Excluding acquired impresses R&D, we now expect total operating expenses for the year to increase approximately 4% to 5%. This increase reflects higher fourth quarter spending to support our product portfolio and pipeline and is in line with fourth quarter increases seen in previous years.

除去收購的令人印象深刻的研發費用，我們現在預計今年的總營運費用將增加約 4% 至 5%。這一成長反映了第四季度支持我們的產品組合和管道的支出增加，並且與前幾年第四季度的成長一致。

These costs are partially offset by savings from our productivity initiatives. We remain confident in our ability to achieve our full year operating margin target of at least 37%. For OI&E, we have increased our estimate from approximately $50 million of expense to approximately $125 million of income due to better-than-expected royalty and interest income.

這些成本被我們生產力計劃的節省所部分抵消。我們對實現至少 37% 的全年營業利潤率目標仍然充滿信心。對於 OI&E，由於特許權使用費和利息收入優於預期，我們將預期收入從約 5,000 萬美元上調至約 1.25 億美元。

As a reminder, our tax rate was impacted by the nondeductible charge for acquired in process R&D, primarily from the Karuna acquisition in the first quarter. Excluding the acquired in-process R&D, we continue to expect estimated underlying non-GAAP tax rate for the full year to be approximately 18%. Taking these updates into effect, we are raising our non-GAAP EPS guidance to a range of $0.75 to $0.95.

提醒一下，我們的稅率受到收購過程中研發的不可扣除費用的影響，主要來自第一季收購 Karuna 的費用。不包括收購的正在進行的研發，我們繼續預計全年的非公認會計原則基礎稅率約為 18%。這些更新生效後，我們將非 GAAP 每股盈餘指引提高至 0.75 美元至 0.95 美元。

In closing, our third quarter results were marked by significantly higher sales across key growth brands. robust cash flow generation and continued financial discipline. As we reestablish our presence in neuroscience with the US launch of we are excited about the long-term opportunity of this brand and its potential to serve more patients.

最後，我們第三季業績的特徵是主要成長品牌的銷售額顯著增加。強勁的現金流產生和持續的財務紀律。隨著我們在美國推出，重新確立了在神經科學領域的地位，我們對該品牌的長期機會及其服務更多患者的潛力感到興奮。

We're looking forward to additional near-term catalysts as our pipeline continues to advance, our solid performance year-to-date supports our raised full-year guidance, and our increased confidence in our ability to drive long-term sustainable growth.

隨著我們的管道繼續推進，我們期待著更多的近期催化劑，我們今年迄今的穩健業績支持我們提高的全年指引，以及我們對推動長期可持續增長的能力的信心增強。

And with that, I'll now turn the call back over to Chuck for Q&A.

現在，我將把電話轉回給查克進行問答。

(Operator Instructions) Evan Seigerman, BMO Capital Markets.

（操作員說明）Evan Seigerman，BMO 資本市場。

Guys, thank you so much for taking the question, and congrats on the progress this quarter. So one for Adam, now that you have approved. Can you walk us through what the next year looks like when it comes to access? I know there's a lot of puts and takes when it comes to Medicaid and commercial. But maybe give us some color as to how we should think about it? Thank you so much.

夥計們，非常感謝您提出問題，並祝賀本季度取得的進展。既然你已經批准了，那就為 Adam 準備一份。您能否向我們介紹明年的訪問情況？我知道在醫療補助和商業方面有很多變化。但也許給我們一些關於我們應該如何思考它的顏色？太感謝了。

Morning, Evan. Adam?

早安，埃文。亞當？

Yeah. Thanks, Evan, for the question. We're very excited about the approval of COBENFY. As you heard from Chris, is the first innovative therapy approved in schizophrenia in decades. And we're very pleased with the label does not carry the atypical antipsychotic class warnings and precautions or a box warning.

是的。謝謝埃文提出的問題。我們對 COBENFY 的批准感到非常興奮。正如您從克里斯那裡聽到的，這是幾十年來第一個被批准用於精神分裂症的創新療法。我們對標籤上沒有非典型抗精神病藥物類警告和注意事項或框架警告感到非常滿意。

And so how we think about this addresses a large market. Remember, there are 1.6 million people treated for schizophrenia each year in the US. We do see this as a 2025 launch with the launch picking up after attaining broad access. We expect to see sales ramp in the second half of the year, and I'll describe those dynamics.

因此，我們如何看待這個問題涉及一個巨大的市場。請記住，美國每年有 160 萬人接受精神分裂症治療。我們確實認為這是 2025 年的一次發布，在廣泛訪問後，發布速度將會加快。我們預計下半年銷售量將會上升，我將描述這些動態。

First and foremost, we're really excited that product is available this week. Our field teams are out now selling. They're engaging with customers. And so we'll see stocking this year. Now access is a gating factor to sales uptake as over 80% of patients are either Medicare or Medicaid.

首先也是最重要的是，我們非常高興該產品將於本週上市。我們的現場團隊現在正在銷售。他們正在與客戶互動。所以我們今年會看到庫存。現在，可及性已成為銷售量的限制因素，因為超過 80% 的患者要么享有醫療保險，要么享受醫療補助。

And just remember, schizophrenia is a fundamentally different market than markets that are highly PBM driven. So we expect to take about a year to achieve 80% to 85% access. It could move a bit faster in Medicaid and we're certainly going to work to accelerate that.

請記住，精神分裂症市場與高度 PBM 驅動的市場有著本質上的不同。所以我們預計需要一年左右的時間才能達到80%到85%的接取率。它在醫療補助中的進展可能會更快一些，我們當然會努力加速這一進程。

So the way to think about is really in a step-wise fashion. In Medicaid, recall roughly half of the states have zero to one step access. And so deep Medicaid P&T meetings will take place over the course of the next several months. We've already seen a few states come online this week. Physicians can prescribe once P&T reviews are completed and we are working to expand access across the remaining states.

所以思考的方式其實是逐步的。在醫療補助中，大約有一半的州有零到一步的存取權。因此，深入的醫療補助 P&T 會議將在接下來的幾個月內舉行。本週我們已經看到一些州上線了。一旦 P&T 審查完成，醫生就可以開處方，我們正在努力擴大其餘州的准入範圍。

Now in Medicare, recall, this is a protected class. So payers have 90 days to make a coverage decision, and we expect to see mandatory coverage determinations in Q1. But in the meantime, physicians can push through medical exemptions before any of these formulary reviews take place.

回想一下，現在在醫療保險中，這是一個受保護的階級。因此，付款人有 90 天的時間做出承保決定，我們預計將在第一季看到強制承保決定。但同時，醫生可以在進行任何這些處方審查之前推動醫療豁免。

Our asset teams have been meeting with payers for some time, and our team without immediately post approval with payers to review the approved label and the response has been very, very positive. So again, we know the work that we need to do to maximize this important launch, and we plan to make this a very big product for our company over time.

我們的資產團隊已經與付款人會面一段時間了，我們的團隊沒有立即與付款人進行批准後審查批准的標籤，但反應非常非常積極。再說一次，我們知道我們需要做哪些工作來最大化這一重要的發布，並且我們計劃隨著時間的推移將其打造成我們公司的一個非常大的產品。

Chris Shibutani, Goldman Sachs.

克里斯·澀谷，高盛。

Great. Thank you very much. Certainly, you've been doing a lot to focus the operating expense profile here. And at the same time, you're seeing improving top line -- where are you in that trajectory in terms of what we should expect 2025? Any early commentary on the shape of 2025 top line dynamics as a function of operating expense would be helpful. Thank you.

偉大的。非常感謝。當然，您已經做了很多工作來關注這裡的營運費用。同時，您看到收入有所改善 - 就我們對 2025 年的預期而言，您處於該軌蹟的哪個位置？任何關於 2025 年營收動態作為營運費用函數的早期評論都會有所幫助。謝謝。

Thanks, Chris. I'll ask David to take that one.

謝謝，克里斯。我會請大衛拿那個。

Yeah, Chris, thanks for the question. And look, we feel really good about the progress we're making on our $1.5 billion savings initiatives that we had in place. And you recall -- we're on track to achieve the majority of that this year.

是的，克里斯，謝謝你的提問。看，我們對我們實施的 15 億美元儲蓄計劃所取得的進展感到非常滿意。你還記得嗎——我們今年有望實現其中的大部分目標。

We also feel really good about the operating margin guidance that we provided of at least 37% both this year and for next year as well. So we're continuing to look for efficiencies in our cost base, and you'll continue to hear more about that. But as it relates to '25, we're going to give you full line guidance like we typically do on our fourth quarter earnings call.

我們也對今年和明年提供的至少 37% 的營業利潤率指導感到非常滿意。因此，我們將繼續尋求成本基礎的效率，您將繼續聽到更多有關這方面的資訊。但由於它涉及 25 年，我們將向您提供全面的指導，就像我們通常在第四季度財報電話會議上所做的那樣。

Thanks, David. Operator, next question, please.

謝謝，大衛。接線員，請下一個問題。

Chris Schott, JPMorgan.

克里斯‧肖特，摩根大通。

Great. Thanks. Just maybe a two-parter on COBENFY. Thank you for all the details on the reimbursement piece. Once reimbursement is in place, can you just talk about how you're thinking about the ramp of the drug from there?

偉大的。謝謝。也許只是 COBENFY 上的兩人合作。感謝您提供有關報銷單的所有詳細資訊。一旦報銷到位，您能否談談您如何考慮從那裡開始增加藥物？

I guess, historically, I think we've seen more gradual launches in schizophrenia, but these are largely assets with similar mechanisms to existing products. I'm just wondering in this case, are you anticipating this could be a faster ramp than we've historically seen given the unmet need and your unique mechanism of action?

我想，從歷史上看，我們已經看到了更多針對精神分裂症的逐漸推出的產品，但這些產品很大程度上是與現有產品具有類似機制的資產。我只是想知道在這種情況下，考慮到未滿足的需求和您獨特的行動機制，您是否預計這可能會比我們歷史上看到的更快？

And then just my second part on the same product is just when you think about the additional line extensions here, what's your confidence in the bipolar 1 opportunity? It's obviously a very large market and live data you've seen in schizophrenia, do you view that as a high probability of success study as you start to ramp that one? Thank you.

然後，我關於同一產品的第二部分是，當您考慮這裡的額外產品線擴展時，您對雙極 1 機會的信心是什麼？這顯然是一個非常大的市場和您在精神分裂症方面看到的即時數據，當您開始加強這項研究時，您認為這項研究成功的可能性很高嗎？謝謝。

Thanks, Chris, and good morning. Adam will take the first part, and then Samit can chime in as well.

謝謝克里斯，早安。亞當將承擔第一部分，然後薩米特也可以插話。

Yeah, Chris, thanks for the question. First thing I'd say is there's really no perfect analog here because unlike previous launches, where you've seen multiple success of approvals, for example, schizophrenia and MDD. That's not going to be the case with COBENFY. COBENFY's approval cadence is going to be in schizophrenia, first in monotherapy than adjunctive therapy.

是的，克里斯，謝謝你的提問。首先我要說的是，這裡確實沒有完美的模擬，因為與之前的發布不同，你已經看到了多次成功的批准，例如精神分裂症和MDD。科本菲的情況不會如此。 COBENFY 的核准節奏將針對精神分裂症，首先是單一療法，然後是輔助療法。

As I said, in terms of the -- as we see the launch an access coming online, really, this is going to be a second half ramp. That's how we see it. So physicians can prescribe today push through medical exemptions before formulary reviews, but we expect to see really full access 80%, 85% access within roughly 12 months post approval.

正如我所說，就我們看到的上線訪問而言，實際上，這將是下半年的斜坡。我們就是這樣看的。因此，今天，醫生可以在處方審查之前推動醫療豁免，但我們預計在批准後大約 12 個月內，將真正實現 80%、85% 的全面准入。

Yeah. And thanks for the question, Chris. If you think about bipolar, so if you think about mania in general, bipolar one, that includes symptoms that are excessive activity as well as the psychotic symptoms of delusion, hallucinations and thought disorders.

是的。謝謝你的提問，克里斯。如果你想到雙極性情感障礙，那麼如果你想到一般的躁狂症，雙相情感障礙，包括過度活動的症狀以及妄想、幻覺和思維障礙的精神病症狀。

Then xanomeline and especially as we think about COBENFY, has demonstrated reduction of these agitation symptoms in Alzheimer's disease as well as in schizophrenia, Alzheimer's data, of course, came from the 1997 study that was published for in the past.

Xanomeline，特別是當我們想到 COBENFY 時，已經證明可以減少阿茲海默症和精神分裂症中的這些躁動症狀，當然，阿茲海默症的數據來自過去發表的 1997 年研究。

So these are all predictive of efficacy potential in bipolar mania. There is no evidence thus far in the studies that have been conducted in the EMERGENT program that shows a worsening of the depressive symptoms. So taken together, we are looking forward to initiation of that program in bipolar mania in the middle of 2025.

因此，這些都是雙極躁症療效潛力的預測。迄今為止，在緊急計劃中進行的研究中沒有證據表明憂鬱症狀惡化。綜上所述，我們期待在 2025 年中期針對躁鬱症患者啟動此計畫。

Just to also add to on top of that beyond bipolar in 2025, we are looking forward to the readout of the ARISE trial, which is the schizophrenia trial. And of course, two additional indications that we will be initiating in 2025 will be AD agitation as well as AD cognition.

除了 2025 年雙相情感障礙之外，我們還期待 ARISE 試驗（即精神分裂症試驗）的公佈。當然，我們將在 2025 年啟動的另外兩個指標是 AD 激動和 AD 認知。

Thanks, Amit. Can we go to our next question, please?

謝謝，阿米特。我們可以繼續下一個問題嗎？

Luisa Hector, Berenberg.

路易莎·赫克托，貝倫貝格。

Hello. Thank you for taking my question. On SOTYKTU, you mentioned the price impact in Q4, but could you add a little more color on the outlook for next year and the access and pricing as we roll into next year? And then perhaps just a reminder of the profile that you're looking for in the psoriatic arthritis trial. Thank you.

你好。感謝您回答我的問題。在 SOTYKTU 上，您提到了第四季度的價格影響，但是您能否對明年的前景以及進入明年時的訪問和定價添加更多色彩？然後也許只是提醒您在銀屑病關節炎試驗中尋找的概況。謝謝。

Thanks, Luisa. Adam can take the first one and then, Samit.

謝謝，路易莎。亞當可以拿第一個，然後是薩米特。

Thanks, Luisa. As we said in the past, the TYK2 performance has been slower than we'd like, and we are making progress on executing against our plan. And that's securing favorable access and ultimately improving performance and execution. Recall, we had 25% access in the first half of the year. We more than doubled that in Q3.

謝謝，路易莎。正如我們過去所說，TYK2 的表現比我們希望的要慢，但我們在執行計劃方面正在取得進展。這就是確保有利的訪問並最終提高績效和執行力。回想一下，今年上半年我們的訪問率為 25%。第三季我們的數字增加了一倍以上。

We now have approximately 50% 0 step edits in the market. And I could say we are having productive conversations with the remaining payers and expect to enable broader access and adoption in 2021. But this comes with significant rebating and gross net impact that will be compensated by increased volume over time. It's going to take a few quarters for that to wash out.

我們現在市場上有大約 50% 的 0 步驟編輯。我可以說，我們正在與剩餘的付款人進行富有成效的對話，並期望在2021 年實現更廣泛的訪問和採用。的增加將得到補償。需要幾個季度的時間才能將其消除。

In fact, in Q3, you saw some of this. We saw some of the pull-through delivered both versus prior year and sequentially when you exclude clinical trials. So this is a market that is going to remain highly competitive, and we're going to continue to work to increase more market share as well as paid prescriptions. But as we exit this year, we will be in a better position versus where we started the year, and we're going to work to be more competitive.

事實上，在第三季度，你已經看到了一些這樣的情況。當您排除臨床試驗時，我們看到與去年相比以及按順序實現了一些拉動。因此，這個市場將保持高度競爭，我們將繼續努力增加更多的市場份額和付費處方。但當我們今年退出時，我們將處於比年初更好的位置，我們將努力提高競爭力。

Thanks for the question, Luisa, for the arthritis part. Remember, we have been able to pull and accelerate the readout of the second study as well. So we are looking forward to the readout towards the end of this year for both poetic politic PSAI within 2024.

感謝路易莎提出關於關節炎部分的問題。請記住，我們也能夠拉動並加速第二項研究的讀出。因此，我們期待今年年底 2024 年詩意政治 PSAI 的結果。

Overall, as you can imagine, since a lot of data has now been generated from a safety and efficacy perspective for SOTYKTU in psoriasis the readout of the program will put us in the right footing as we think about the competitor profile versus as well. So looking forward to that, we have no concerns from a safety perspective as we've said, so hopefully, the studies read out positive, that will lead to a filing in 2025.

總體而言，正如您可以想像的那樣，由於現在已經從SOTYKTU 治療銀屑病的安全性和有效性角度生成了大量數據，因此該計劃的讀出將使我們在考慮競爭對手概況時處於正確的地位。因此，我們對此充滿期待，正如我們所說，從安全角度來看，我們並不擔心，因此希望研究結果是正面的，這將導致在 2025 年提交申請。

Great, thank you. Next question, please, operator.

太好了，謝謝。接線員，請下一個問題。

Geoff Meacham, Citibank.

傑夫‧米查姆，花旗銀行。

Morning, everyone. Thanks so much for the question. For Chris or Samit on the milvexian program, I know you guys did talk about the use of -- the potential to upsize the trial previously.

早安，大家。非常感謝您的提問。對於 milvexian 計劃中的 Chris 或 Samit，我知道你們確實談論過使用——之前擴大試驗規模的潛力。

But what would you say is the cause for the lower event rate? Does this change the risk profile? We know that GLP-1s have an impact, for example, in cardiometabolic trials. You think changes there commercially could have changed the event rate in your study? Thank you very much.

但您認為事件發生率較低的原因是什麼？這會改變風險狀況嗎？我們知道 GLP-1 具有影響力，例如在心臟代謝試驗中。您認為商業上的改變可能會改變您研究中的事件發生率？非常感謝。

Thanks, Geoff. I'll start, and then I'll turn it over to Samit. Let me just say at the outset, Geoff, that we're encouraged by what we're seeing with this program. Just a reminder, we're developing milvexian because there remains high unmet need for patients in anti-coagulation. That's particularly true in atrial fibrillation, where as I think you know, this is an area where 40 million individuals worldwide have atrial fibrillation.

謝謝，傑夫。我先開始，然後把它交給薩米特。傑夫，我首先要說的是，我們對這個計劃所看到的一切感到鼓舞。提醒一下，我們正在開發米爾維鮮，因為患者的抗凝血治療需求仍然沒有被滿足。對於心房顫動尤其如此，我想您也知道，在這個領域，全世界有 4000 萬人患有心房顫動。

And that despite the success of Factor Xa like Eliquis, about 40% of those patients remain on or undertreated due to the risk of bleeding. And we believe milvexian has the potential to improve the outcome for these patients. The update that we provided today is really intended to give some context to the decision to increase the sample size given the encouraging blended event rates that we're seeing at this point in the study.

儘管 Xa 因子（如 Eliquis）取得了成功，但由於出血風險，約 40% 的患者仍在接受治療或治療不足。我們相信米爾維鮮有潛力改善這些患者的治療結果。鑑於我們目前在研究中看到的令人鼓舞的混合事件發生率，我們今天提供的更新實際上是為了為增加樣本量的決定提供一些背景資訊。

This is a potentially important medicine. We want to do everything we can to ensure that the program continues to read out in 2027. But before I turn it over to Samit. I want to leave you with, we're encouraged by what we're seeing here, and we look forward to seeing this study come to its outcome in 2027. Samit?

這是一種潛在的重要藥物。我們希望盡一切努力確保該計劃在 2027 年繼續宣讀。留給您的留言是，我們對這裡所看到的情況感到鼓舞，我們期待看到這項研究在 2027 年得出結果。

Yeah. Thanks, Chris. And Geoff, just extending from where Chris left off from an encouraging point of view, remember where we started the program from. What we have seen from trial in AF, it was very clear that one of the key drivers of the outcome was the dose.

是的。謝謝，克里斯。傑夫（Geoff）從克里斯停止的地方出發，從令人鼓舞的角度出發，記住我們從哪裡開始這個計劃。我們從 AF 試驗中看到，很明顯，結果的關鍵驅動因素之一是劑量。

We started the milvexian program with well-designed Phase 2 studies that led us to pick the right doses for our Phase 3 programs in AF as well as in combination with agents in ACS as well as SSP. Secondly, our event rate is lower compared to what we had designed the study for at the current time. And that gives us the reason to increase the sample size, which you will see the numbers when we update centrals.gov.

我們透過精心設計的 2 期研究啟動了 milvexian 項目，這些研究使我們為 AF 的 3 期項目以及與 ACS 和 SSP 藥物的聯合選擇了正確的劑量。其次，與我們目前設計研究的目的相比，我們的事件發生率較低。這給了我們增加樣本量的理由，當我們更新centrals.gov時您將看到這些數字。

Thirdly, as we think about why the study was started, the genic study was stopped because the DMC reviewed the data and saw almost more than -- almost 3 times the event rate on the investigation arm in that study. Our study is periodically reviewed by the DMC.

第三，當我們思考為什麼要開始這項研究時，基因研究被停止了，因為 DMC 審查了數據，發現該研究中調查組的事件發生率幾乎是研究的 3 倍以上。 DMC 會定期檢視我們的研究。

There are no indications from the DMC that we should go any other route and they are supportive of continuing the study at this time. We truly are encouraged by all of this. And as you know, ACS as well as the SSP programs are slated to read out in 2026, and we are on track for that.

DMC 沒有表明我們應該走任何其他路線，他們支持目前繼續進行研究。這一切確實讓我們深受鼓舞。如您所知，ACS 和 SSP 計劃預計於 2026 年公佈，我們正在朝著這個目標邁進。

Great. Thanks for the background. Next question please, operator.

偉大的。謝謝你的背景。接線員，請下一個問題。

Carter Gould, Barclays.

卡特·古爾德，巴克萊銀行。

Great. Thanks for taking the questions in solid print this morning. Maybe I don't mean to hammer on it again, but just wanted to follow up on the prior question for Samit there. With the increased patient enrollment, will there be any shift in the criteria or enrichment of patients away from the of our proximal segments.

偉大的。感謝您今天早上以印刷體形式提出問題。也許我不想再重複這個問題，只是想跟進薩米特之前提出的問題。隨著患者入組人數的增加，患者的標準或豐富程度是否會發生變化，遠離我們的近端區段。

I mean, I appreciate your commentary on what happened to your competitor but at the same conversation at ESC, there was talk about the challenges in those populations given especially what seems to be going on here at the event rate. Any color would be appreciated. Thank you.

我的意思是，我很欣賞你對你的競爭對手所發生的事情的評論，但在ESC 的同一次談話中，人們談論了這些人群面臨的挑戰，特別是考慮到這裡似乎正在發生的事件發生率。任何顏色都會受到讚賞。謝謝。

Yes. Thank you, Carter. There are no plans to change any of these criteria. We will continue to observe them and the study will continue as is, except for the change in the sample size.

是的。謝謝你，卡特。沒有計劃改變任何這些標準。我們將繼續觀察它們，研究將按原樣繼續進行，除了樣本量變化。

Great. Let's move to the next question, please.

偉大的。請讓我們進入下一個問題。

Mohit Bansal, Wells Fargo.

莫希特·班薩爾，富國銀行。

Hi, this is [Serena] on for Mohit. We wanted to dig more into the KarXT development plans as it relates to cognition. Perhaps starting with the AD psychosis trial, I was wondering if it will still have the 3 times in one day dosing and longer titration period.

大家好，我是 Mohit 的 [Serena]。我們希望深入研究與認知相關的 KarXT 開發計劃。也許從AD精神病試驗開始，我想知道它是否還會有一日3次給藥和更長的滴定期。

And then moving on to the cognition trial. Was wondering what this could look like, like would it need to be longer than the EMERGENT studies? And do you plan to enrich for patients cognitively impaired at baseline? Thank you.

然後繼續進行認知試驗。想知道會是什麼樣子，是否需要比緊急研究更長的時間？您是否計劃為基線認知受損的患者提供豐富的服務？謝謝。

Thanks for the question, [Serena]. Samit?

謝謝你的提問，[瑟琳娜]。薩米特？

Yeah. Thank you, Serena, for the question. So we're looking forward to, obviously, the initiation of three Phase 3 programs next year, one in AD agitation, second in bipolar mania, third in the AD cognition program.

是的。謝謝小威的提問。因此，顯然，我們期待明年啟動三個第三階段項目，一個是 AD 躁動項目，第二個是雙相躁症項目，第三個是 AD 認知項目。

The reason for belief of course, is the dual mechanism of action in terms of M1 and M4 direct agonism that is obviously associated with xanomeline, as well as the available data from the old studies that were conducted with xanomeline that already showed the right trend in terms of the cognition improvement in those studies.

當然，相信的原因是 M1 和 M4 直接激動的雙重作用機制，這顯然與 xanomeline 相關，以及使用 xanomeline 進行的舊研究的可用數據，這些數據已經顯示出正確的趨勢這些研究中的認知改善方面。

Your question around the 3 times a day dosing right now that is built into the AD psychosis program. We are working on the BID dosing for these patients. And there will be instituted in the new study that we will start in the three indications that I talked about as well as we are thinking about how we will institute a bridging program so that we can bring it back into the AD psychosis program as well. Overall, in a good track and certainly looking forward now to the readout of the ARISE study next year.

你的問題是關於 AD 精神病計畫中目前每天 3 次給藥的問題。我們正在研究這些患者的 BID 劑量。在新的研究中，我們將從我談到的三個適應症開始，我們正在考慮如何制定一個橋接計劃，以便我們也可以將其帶回 AD 精神病計劃中。總體而言，進展順利，現在當然期待明年 ARISE 研究的結果。

Great, thanks, Samit. Let's take our next question, please.

太好了，謝謝，薩米特。請讓我們回答下一個問題。

Chun Chung, UBS.

春鐘，瑞銀。

Morning, guys. Thanks for taking my question. Just one on the recent data. We saw an ORR of 21% across a bunch of solid tumors. Can you perhaps talk about efficacy as regard to durability that you're seeing here with the product? And what tumor types are you going to be prioritizing? Thank you.

早安，夥計們。感謝您提出我的問題。只是最近的數據之一。我們發現一堆實體瘤的 ORR 為 21%。您能否談談您在這裡看到的產品的耐用性功效？您將優先考慮哪些腫瘤類型？謝謝。

Thanks for the question, Chun. Samit?

謝謝你的提問，春。薩米特？

Thank you for the question. Really, actually, very encouraging data from our perspective. We look at it from a breakdown in terms of the tumor types that were enrolled and the two that stood out from that program thus far.

謝謝你的提問。從我們的角度來看，確實是非常令人鼓舞的數據。我們從入組的腫瘤類型和迄今為止在該計劃中脫穎而出的兩種腫瘤類型的細分來看待它。

Our non-small cell lung cancer, where you -- if you look at just the non-small cell lung cancer cohort, the overall response rate is about 31% with a very good durability. The one thing to note in that program is that responses do occur late -- so it's more of a long-term duration of control of these patients on the drug and most patients actually have disease control for a very long period.

我們的非小細胞肺癌，如果你只看非小細胞肺癌隊列，整體緩解率約為 31%，並且具有非常好的持久性。該計劃中需要注意的一件事是，反應確實發生得很晚，因此這些患者對藥物的控制更多的是長期持續時間，而且大多數患者實際上在很長一段時間內都得到了疾病控制。

As you saw, the duration of response is already 10.5 months. Then if you take about -- talk about the stable diseases as well, that also constitutes about the similar trajectory from our non-small cell lung cancer population. The second thing that was very encouraging was looking at the pancreatic cancer patient population and at the right doses at the 400 and 600-milligram dose, we saw actually increased response rates, again, a very good durability.

正如您所看到的，回應持續時間已經是 10.5 個月。然後，如果你也談論穩定的疾病，這也構成了我們的非小細胞肺癌族群的類似軌跡。第二件非常令人鼓舞的事情是觀察胰臟癌患者群體，在 400 毫克和 600 毫克劑量的正確劑量下，我們看到實際上反應率有所提高，而且具有非常好的持久性。

Some patients now going all the way almost up to a year. And so those two indications look very promising, and we are looking forward to giving you update on next year in terms of the later phase development for this program.

有些患者現在已經持續了將近一年的時間。因此，這兩個跡像看起來非常有希望，我們期待為您提供明年有關該計劃後期開發的最新資訊。

Great, thanks. Let's move to the next question, please.

太好了，謝謝。請讓我們進入下一個問題。

Steve Scala, Cowen.

史蒂夫·斯卡拉，考恩。

Thank you so much. I have two points, and there are really -- two questions. They're just really clarifications but 1 percentage point of Bristol revenue growth is about $500 million. And that's the amount that Bristol is increasing its guidance that's roughly equivalent to what REVLIMID So is the increase solely attributed to REVLIMID?

太感謝了。我有兩點，而且確實有兩個問題。它們只是真正的澄清，但布里斯托營收成長 1 個百分點約為 5 億美元。這就是布里斯托增加其指導的金額，大致相當於瑞復美 (REVLIMID) 那麼，增加的金額僅歸因於瑞復美 (REVLIMID) 嗎？

And then secondly, and I apologize for going back to Asyndexian -- but the AFIP trial had a lower-than-expected event rate and failed. Why is a lower-than-expected event rate in the milvexian trial encouraging? It as easily could be a risk, I would think. I understand the DSMB point. So any clarity would be appreciated.

其次，我為回到 Asyndexian 表示歉意 - 但 AFIP 試驗的事件發生率低於預期並失敗了。為什麼 milvexian 試驗中低於預期的事件發生率令人鼓舞？我認為這很容易成為一種風險。我理解 DSMB 的觀點。因此，如有任何澄清，我們將不勝感激。

Thanks for the question, Steve. I'll ask David to start, and then we'll flip over to Samit.

謝謝你的提問，史蒂夫。我將請大衛開始，然後我們將轉向薩米特。

Yeah, Steve, thanks for the question. And look, we saw a strong performance in our growth portfolio as we talked about. And that's why we also saw good performance and raised the REVLIMID guidance to $5.5 billion, and that caused us to raise the full year outlook 5% growth versus prior year on a reported 6% excluding currency.

是的，史蒂夫，謝謝你的提問。看，正如我們所討論的，我們看到了我們的成長投資組合的強勁表現。這就是為什麼我們也看到了良好的業績，並將 REVLIMID 指引提高至 55 億美元，這導致我們將全年預期增長較上一年提高 5%，據報道，不包括貨幣的增長率為 6%。

The other thing I would note, too, is as I said on the call, we have generic entry coming in on Sprycel Abraxane and POMALYST. The already facing generic as is POMALYST. So we just want to make sure that people update their models for the additional generic erosion in the fourth quarter. But net-net, when we put all that together, as we said, we raised our revenue guidance as a result.

我還要指出的另一件事是，正如我在電話中所說，我們有 Sprycel Abraxane 和 POMALYST 的通用條目。已經面臨的仿製藥是 POMALYST。因此，我們只是想確保人們更新他們的模型，以應對第四季度額外的通用侵蝕。但是，當我們將所有這些放在一起時，正如我們所說，我們因此提高了收入指導。

And Steve, thank you. This is Samit. Great question. Just to recall, if you go back to study and we look at the event rate for then we look at the rate for apixaban. Apixaban was 1.03.

史蒂夫，謝謝你。這是薩米特。很好的問題。回想一下，如果您回去研究，我們會查看事件發生率，然後我們會查看阿哌沙班的發生率。阿哌沙班為 1.03。

Asyndexian was 2.33, if I remember, and even more so. And then if you think about what we have planned in the milvexian study is 1.33.

如果我記得的話，Asyndexian 是 2.33，甚至更高。然後，如果您考慮我們在 milvexian 研究中計劃的值是 1.33。

So overall, if you think about it, we are looking at a blended event rate as Chris mentioned, which is much lower than the planned event rate. So overall, we are encouraged by this and not necessarily thinking that it's an issue. As I said earlier, DMC continues to look at it, and they are okay with us continuing this study, and we are increasing the sample size.

因此，總的來說，如果您考慮一下，我們正在考慮克里斯提到的混合事件發生率，這比計劃的事件發生率低得多。總的來說，我們對此感到鼓舞，但不一定認為這是個問題。正如我之前所說，DMC 會繼續關注這個問題，他們同意我們繼續這項研究，並且我們正在增加樣本量。

Great. Thanks for the added context. Next question, please.

偉大的。感謝您添加的上下文。請下一個問題。

Courtney Breen, Bernstein.

考特尼·布林，伯恩斯坦。

Thank you so much for the question. Another question just on the COBENFY launch. What I wanted to make sure we were able to understand is because some of the practicalities around kind of a patient receiving a script and kind of the doctor choosing that patient to prescribe to.

非常感謝你的提問。另一個關於 COBENFY 發布的問題。我想確保我們能夠理解的是，因為患者收到腳本以及醫生選擇為該患者開處方的一些實際情況。

Can you share some of the context on the warnings and precautions in the label, particularly around liver and how many patients you practically expect to be managed through these challenges. I do note that obviously, there isn't the box label warning, but there are some warnings that require extra physician attention. And so can you just speak to some of those challenges?

您能否分享一下標籤中警告和預防措施的一些背景信息，特別是關於肝臟的警告和預防措施，以及您實際上期望有多少患者能夠應對這些挑戰。我確實注意到，顯然，包裝盒標籤上沒有警告，但有一些警告需要醫生額外注意。那麼您能談談其中一些挑戰嗎？

Thanks, Courtney. Adam?

謝謝，考特尼。亞當？

Yeah. Courtney, thanks for the question. Just as you know, COBENFY offers efficacy that at least as good or better than Zyprexa, without the significant adverse events that have plagued the dyslipidemia, EPS sedation, those are the ones where they lead to the greatest level of discontinuation and why you see patients stop treatment and physicians rechallenge with another agent.

是的。考特尼，謝謝你的提問。如您所知，COBENFY 的療效至少與 Zyprexa 一樣好或更好，並且沒有困擾血脂異常、EPS 鎮靜的重大不良事件，這些不良事件會導致最大程度的停藥，也是您看到患者的原因停止治療，醫生重新使用另一種藥物。

We're very pleased with the label, and we're just at the beginning, but the progress and the feedback that we're hearing have been very, very positive. When you look at some of the monitoring that's in the label, remember, the large majority of patients have had recent lab assessments. So we don't anticipate this to be a barrier.

我們對這個標籤非常滿意，我們才剛開始，但我們聽到的進展和回饋都非常非常積極。當您查看標籤中的一些監測時，請記住，絕大多數患者最近都進行過實驗室評估。因此，我們預計這不會成為障礙。

In the label, this is recommended. It's not a mandated and lab assessments are very common in this patient population. Most antipsychotics today recommend lab assessments. So we don't see it's an issue for adoption. And when you look at renal impairment in patients with schizophrenia, in the mid-single digits.

在標籤上，這是推薦的。這不是強制性的，實驗室評估在該患者群體中很常見。如今大多數抗精神病藥物都建議進行實驗室評估。所以我們不認為這是採用的問題。當你觀察精神分裂症患者的腎功能損害時，其腎功能損害程度為個位數。

So taken together, we are very pleased with the efficacy profile that is unique to COBENFY based on its mechanism of action and its best-in-category safety profile.

綜上所述，我們對 COBENFY 基於其作用機制和同類最佳安全性的獨特功效感到非常滿意。

And just to add to what Adam is saying. You will also see the data on longer-term studies, EMERGENT-4 and EMERGENT-5, hundreds of patients who have been treated through those as well. And the safety profile continues to remain the same, but certainly efficacy maintained. So that, in addition, gives us a lot of confidence in the overall profile for as Adam said.

只是為了補充亞當所說的內容。您還將看到長期研究、EMERGENT-4 和 EMERGENT-5 的數據，以及數百名透過這些研究接受治療的患者。安全性繼續保持不變，但功效肯定保持不變。此外，正如亞當所說，這也讓我們對整體形象充滿信心。

Great, thank you both. Next question, please.

太好了，謝謝你們兩個。請下一個問題。

Seamus Fernandez, Guggenheim Securities.

謝默斯·費爾南德斯，古根漢證券公司。

Thanks very much for the question. So I wanted to just get a sense for your enthusiasm for the upcoming data at ACR for your CD19 asset? And how you see the evolution of a potential market for intensive immunologic treatments like this versus the potential for whether it be T cell engagers or bispecific products with a similar type target profile, but perhaps less efficacy.

非常感謝您的提問。所以我想了解一下您對 ACR 即將發布的 CD19 資產數據的熱情？您如何看待此類強化免疫療法的潛在市場的演變，以及 T 細胞接合劑或具有相似類型靶點特徵但可能療效較差的雙特異性產品的潛力。

And then just the second question is on the 2025 dynamics. Just hoping to get maybe a little bit of a better sense of the sort of pushes and pulls on IRA. I know you've said that you expect it to be largely neutral, but it does seem like there are opportunities to potentially increase volume in that context. And I just wanted to clarify whether or not any volume benefits are incorporated into your assumptions around that neutral assumption? Thanks.

第二個問題是關於 2025 年的動態。只是希望能夠更了解愛爾蘭共和軍的推動和拉動。我知道你說過你預計它在很大程度上是中性的，但在這種情況下似乎確實有機會增加交易量。我只是想澄清一下，您圍繞中性假設的假設是否包含任何數量效益？謝謝。

Thanks for the question, Seamus. Samit, maybe you can start and then turn it over to Adam.

謝謝你的提問，西莫。薩米特，也許你可以開始，然後把它交給亞當。

Thanks, Seamus. Great question. And let me start -- there are two parts on the drug side of things. Let's start with our cell therapies, truly a transformational approach to treatment of autoimmune diseases as we've seen with the emerging data from others -- and now we will have a chance to present our own data.

謝謝，西莫。很好的問題。讓我開始——藥物方面有兩個部分。讓我們從我們的細胞療法開始，這確實是一種治療自體免疫疾病的變革性方法，正如我們從其他人的新數據中看到的那樣，現在我們將有機會展示我們自己的數據。

Just remember one thing. We just -- we started our study at the end of November last year. First patient was actually dosed in November of 2023. And so we are looking forward to presentation of that data -- there are a few things that you may want to notice as we present that data. Number one, who are the patients who are enrolled in these studies and what is the severity of the disease that they have been enrolled with.

只要記住一件事。我們去年 11 月底就開始了我們的研究。第一位患者實際上是在 2023 年 11 月接受了給藥。第一，誰是參加這些研究的患者以及他們所參與的疾病的嚴重程度是什麼。

And then secondly, after treatment, what happens to the B cell dynamics in terms of the loss of B cell or depletion of B cells as well as reemergence? And then what is the impact on their remission in terms of stopping the treatment that they were on for immunomodulators, immunosuppressants. And then, of course, what is the safety profile.

其次，治療後，B 細胞的動態變化（B 細胞流失或耗竭以及重新出現）會發生什麼變化？那麼停止免疫調節劑、免疫抑制劑治療對他們的緩解有何影響。當然，還有什麼是安全性。

Remember, many of these patients will have underlying organ damage. And so that will be important to keep in mind as you look at the data. These are small number of patients, but we will be able to update these data again at ASH with additional patients, longer follow-up and even additional indications.

請記住，這些患者中的許多人會有潛在的器官損傷。因此，在查看數據時記住這一點很重要。這些患者數量很少，但我們將能夠在 ASH 上再次更新這些數據，包括更多患者、更長的追蹤時間甚至更多適應症。

Second part of your question was around -- how do you see these as cost to T cell engagers bispecifics. I think that's an important element that we will need to consider and new publications have recently come out using BCMA-directed therapy, and there is a case report for CD19 directed T-cell engager as well in the past. And they look very promising, encouraging.

你的問題的第二部分是——你如何看待這些 T 細胞接合者雙特異性的成本。我認為這是我們需要考慮的一個重要因素，最近發表了使用 BCMA 定向療法的新出版物，並且過去也有關於 CD19 定向 T 細胞接合器的病例報告。他們看起來非常有前途、令人鼓舞。

We'll have to see which patients should go on to car cell therapies in the future and which patients should go through with a T-cell engager and bispecifics because bispecifics will require repeated administration at a certain point in time, either weekly, by weekly or every four weeks. And we'll have to define then the duration of that treatment. So all of those questions are still to be answered for T cell engagers.

我們必須了解哪些患者將來應該繼續接受汽車細胞療法，哪些患者應該接受 T 細胞接合劑和雙特異性藥物，因為雙特異性藥物需要在某個時間點（每週或每週）重複給藥或每四個星期一次。然後我們必須定義治療的持續時間。因此，所有這些問題仍有待 T 細胞參與者解答。

You recall we have a BCMA T cell engager that we stopped develop in multiple myeloma. But next year, in 2025, you will see a study -- a couple of studies starting in a couple of indications that we will certainly test out the theory for application of BCMA-directed bispecific in those diseases. Adam?

您還記得我們有一個 BCMA T 細胞接合器，我們已停止在多發性骨髓瘤中開發該接合器。但明年，也就是 2025 年，您將看到一項研究——幾項研究，從幾個跡象開始，我們肯定會測試 BCMA 導向的雙特異性在這些疾病中的應用理論。亞當？

Yes. So just the question around the changes to the benefit design as it relates to IRA. So with the elimination of the coverage gap, we expect favorability with Eliquis next year due to redesign with the elimination of the coverage gap.

是的。因此，問題在於與 IRA 相關的福利設計的變化。因此，隨著覆蓋範圍差距的消除，我們預計明年對 Eliquis 的青睞是由於重新設計並消除了覆蓋範圍差距。

But that's going to be offset largely by products like REVLIMID and POMALYST in the catastrophic phase, where we're now responsible for 20%. So there are pushes and pulls with IRA opportunities, including patient affordability, also with changes in the Part D benefit design. But taken together, we see this as essentially net neutral across our portfolio.

但這將在很大程度上被災難性階段的 REVLIMID 和 POMALYST 等產品所抵消，我們現在負責 20%。因此，IRA 機會存在推動和拉動，包括患者的負擔能力，以及 D 部分福利設計的變化。但總的來說，我們認為這在我們的投資組合中基本上是淨中性的。

Thanks, Adam. Thank you. Let's move to the next question, please, operator.

謝謝，亞當。謝謝。接線員，請讓我們進入下一個問題。

Matt Phipps, William Blair.

馬特·菲普斯，威廉·布萊爾。

Good morning. Thanks for taking my question. I was wondering how you all view the market opportunity for the GPRC5D CAR-T maybe relative to Abecma, given you've now moved the 5D program into a second-line Phase 2 trial, do you think the profile is strong enough to really challenge a BCMA CAR-T? Or would it be used after a BCMA CAR-T. And Chris, what type of [candy] are you going with tonight?

早安.感謝您提出我的問題。我想知道你們如何看待 GPRC5D CAR-T 可能相對於 Abecma 的市場機會，考慮到你們現在已經將 5D 項目轉移到二線第 2 期試驗，你們認為這個形像是否足夠強大，足以真正挑戰BCMA CAR-T？或者它會在 BCMA CAR-T 之後使用嗎？克里斯，今晚你要吃什麼類型的[糖果]？

So we'll start with Adam, and Samit, you can chime in as well.

我們將從 Adam 開始，Samit，你也可以插話。

Yeah. So, we started the study with our CPRC5D agent will be moving that quickly into Phase 3 registrational trials. We are very encouraged with what we've seen thus far. Remember, this is going to be an important asset that is going to be used after BCMA CAR-T treatment is a competitive environment we know.

是的。因此，我們開始與 CPRC5D 藥物進行研究，並將迅速進入第 3 階段註冊試驗。我們對迄今為止所看到的情況感到非常鼓舞。請記住，這將成為我們所知的 BCMA CAR-T 治療競爭環境之後將使用的重要資產。

But with a single dose -- and the toxicity profile that we are seeing thus far with GPRC5D we think we have a really great opportunity here with this asset to be another leading cell therapy asset for our company.

但是，透過單劑量以及迄今為止我們在 GPRC5D 中看到的毒性特徵，我們認為我們有一個非常好的機會，使該資產成為我們公司的另一個領先的細胞治療資產。

Thanks, Adam. And Matt, I'm a (inaudible) guy, so -- thanks for that important insight. Next question, please.

謝謝，亞當。馬特，我是一個（聽不清楚）人，所以——感謝您的重要見解。請下一個問題。

David Risinger, Leerink Partners.

大衛‧瑞辛格 (David Risinger)，Leerink 合夥人。

Yes. Thank you very much. So I'll just keep it to one high-level question, please. So Chris, I think you mentioned a few times on the call that you see Bristol-Myers as a sustainable growth company. Could you just provide some more context on that, your sustainable growth expectations in light of 2026 revenue pressures and the end of the diabetes royalty stream. Thanks very much.

是的。非常感謝。因此，我將只討論一個高級問題。克里斯，我想你在電話會議上多次提到你認為百時美施貴寶是一家可持續發展的公司。鑑於 2026 年的收入壓力和糖尿病特許權使用費流的結束，您能否提供更多相關背景資訊、您的永續成長預期。非常感謝。

Thanks for the question, David. Yes. Look, as we have said consistently, our North Star since I took over as CEO in November has been that we execute in the short term and stay focused on building a company that will deliver long-term sustained growth and shareholder value, particularly as we work our way through the middle of the decade exiting with a very strong growth profile towards the end of the decade.

謝謝你的提問，大衛。是的。看，正如我們一直所說的那樣，自從我11 月接任執行長以來，我們的北極星一直是我們在短期內執行並繼續專注於建立一家能夠實現長期持續成長和股東價值的公司，特別是當我們我們將在本世紀中期努力工作，並在本世紀末以非常強勁的成長態勢退出。

And as I think about the way that we continue to build confidence in that, I would say, I'd highlight three things. First, we have a young portfolio of growing assets. You've seen that in the quarterly results. And we're squarely focused on continuing to drive performance in this growth profile. We've got products like COBENFY, which just launched very early in its life cycle.

當我思考我們如何繼續建立信心時，我想說，我要強調三件事。首先，我們擁有不斷成長的年輕資產組合。您已經在季度業績中看到了這一點。我們完全專注於繼續推動這一成長模式的表現。我們有像 COBENFY 這樣的產品，它剛剛在生命週期的早期推出。

Clearly, schizophrenia is important. You're going to see additional indications, notably the adjunctive indication in 2025. Breyanzi continues to show very solid and strong growth in cell therapy. And remember, that's at the tip of a pipeline of assets we've discussed this morning in fact, that look promising, including CD19 and GPRC5D.

顯然，精神分裂症很重要。您將看到更多的適應症，特別是 2025 年的輔助適應症。請記住，事實上，這是我們今天早上討論的一系列資產的尖端，看起來很有希望，包括 CD19 和 GPRC5D。

We saw continued steady growth for Reblozyl and CAMZYOS. We would expect that to continue. Those two products have line extensions coming up in the next 12 months. And of course, we've talked considerably about Opdualag and nivo subcu providing a foundation for our I-O business through the end of this decade and into the next.

我們看到 Reblozyl 和 CAMZYOS 持續穩定成長。我們預計這種情況會持續下去。這兩款產品將在未來 12 個月內進行產品線擴展。當然，我們已經大量討論了 Opdualag 和 nivo subcu，它們為我們的 I-O 業務提供了本十年末和下一個十年的基礎。

And then when you step back from that, the second thing that's encouraging is we continue to see very good progress in our late-stage pipeline. We've talked about milvexian and the encouraging progress of that program in AFib as well as the two other additional indications we're running in parallel.

然後，當你退後一步時，第二件令人鼓舞的事情是我們繼續看到我們的後期管道取得了非常好的進展。我們已經討論了 milvexian 和該專案在 AFib 中令人鼓舞的進展，以及我們正在並行運行的其他兩個附加適應症。

We're excited about LPA1. And remember, we have multiple Phase 2 programs that have demonstrated efficacy and safety for that program. So we're excited to see that play out. Iberdomide and mezigdomide give us opportunities in multiple myeloma. And these are products that have important readouts over the next 12 to 24 months.

我們對 LPA1 感到非常興奮。請記住，我們有多個第二階段計劃，這些計劃已證明該計劃的有效性和安全性。所以我們很高興看到這一結果。伊莎貝拉胺和美齊格多胺為我們治療多發性骨髓瘤提供了機會。這些產品在未來 12 至 24 個月內具有重要的讀數。

So we've got continued excitement in the late-stage pipeline. And then across all of our businesses, we've maintained financial discipline. That gives us the ability to have a solid balance sheet. Our P&L looks good, and that gives us strategic flexibility to continue to invest both in our internal program as well as source innovation externally as we did with the Karuna acquisition, for example, in December.

因此，我們對後期管道持續感到興奮。在我們所有的業務中，我們都保持了財務紀律。這使我們有能力擁有穩健的資產負債表。我們的損益表看起來不錯，這為我們提供了戰略靈活性，可以繼續投資於我們的內部計劃以及外部創新，就像我們在 12 月收購 Karuna 時所做的那樣。

So if I add it up, I think those are the core components of how we continue to build conviction in the sustainable growth that we're looking to drive for the company.

因此，如果我把它加起來，我認為這些是我們如何繼續建立我們希望推動公司可持續成長的信念的核心組成部分。

Great. Thanks, Chris. Let's move to our next question, please.

偉大的。謝謝，克里斯。請讓我們進入下一個問題。

Akash Tewari, Jefferies.

阿卡什·特瓦里，杰弗里斯。

Hey, thanks so much. Given that there's been reports of J&J shutting down their cardiometabolic division, is there any potential for your team to renegotiate your partnership with them around and on subcu OPDIVO, your team doesn't seem to be guiding for branded reps beyond the FDA regulatory protection which is a market contract to what Merck is communicating on subcu KEYTRUDA. Any color on why your team seems to be more conservative here? Thank you.

嘿，非常感謝。鑑於有報道稱強生關閉了其心臟代謝部門，您的團隊是否有可能圍繞 subcu OPDIVO 與他們重新談判合作夥伴關係，您的團隊似乎不會為超出 FDA 監管保護的品牌代表提供指導是默克在subcu KEYTRUDA 上傳達的市場合約。有什麼顏色可以解釋為什麼你的團隊在這裡似乎更保守嗎？謝謝。

So do you mind repeating the second question?

那你介意重複第二個問題嗎？

Yeah. In terms of protections around subcu OPDIVO in terms of the length of duration versus what Merck is communicating on subcu KEYTRUDA?

是的。就 subcu OPDIVO 的保護期限而言，與默克在 subcu KEYTRUDA 上傳達的內容相比？

Got it. Sorry, we just missed that. So with respect to J&J, no change in our partnership with J&J. J&J has communicated, they continue to be squarely supportive and engaged on the milvexian program. And in fact, their work on the ongoing Phase 3 programs continues to be very, very good, and we've got a very good relationship with J&J on that program. And then Adam, I'll ask you to take the second.

知道了。抱歉，我們剛剛錯過了。因此，就強生而言，我們與強生的合作關係並沒有改變。強生公司已表示，他們將繼續堅決支持並參與 milvexian 計畫。事實上，他們在正在進行的第三階段專案上的工作仍然非常非常好，我們在這個專案上與強生公司建立了非常良好的關係。然後亞當，我會請你接受第二個。

Yes. Regarding the subcu. First, we look forward to the PDUFA date for the nivolumab subcu in late December. Launch planning is progressing very well. And we talked about shifting at least 30% to 40% of the total US OPDIVO business, we can do that ahead of the LOE, which is in late 2028.

是的。關於子庫。首先，我們期待 12 月底 nivolumab subcu 的 PDUFA 日期。發射計畫進展順利。我們談到了轉移美國 OPDIVO 業務總量的至少 30% 至 40%，我們可以在 2028 年底 LOE 之前做到這一點。

As far as the extension of the I-O franchise. This is what excites us potentially about this product because not only does subcu address the treatment burden for patients and physicians with a 3- to 5-minute fusion time as well as in opposite injection what this is going to do based on the broad patent state for the subcu, it will allow us to extend our franchise into the next decade.

至於 I-O 特許經營權的擴展。這就是這款產品讓我們興奮的地方，因為 subcu 不僅可以透過 3 到 5 分鐘的整合時間來解決患者和醫生的治療負擔，而且在相反的注射中，根據廣泛的專利狀態，這將起到什麼作用對於subcu 來說，這將使我們能夠將我們的特許經營權擴展到下一個十年。

James Shin, Deutsche Bank.

詹姆斯‧辛，德意志銀行。

Hi, guys. Thanks for taking our question. I just want to go back to milvexian real quick. I really appreciate the update on the stroke and embolism event rates. But was there any separation between the arms? And perhaps even more importantly, do you have any color on bleed rates. Thank you.

嗨，大家好。感謝您提出我們的問題。我只想快點回到米爾維西安。我非常感謝中風和栓塞事件發生率的最新資訊。但手臂之間有分離嗎？也許更重要的是，您對出血率有什麼看法嗎？謝謝。

Thanks for the question, James. Samit?

謝謝你的提問，詹姆斯。薩米特？

Thank you, James, for the question. Obviously, we can't look at those from a by-arm perspective. This is a blinded study. We don't get to see the data that way. It's a blended event rate that we can talk about and we don't get to the specifics of the general profile of the drug at this time.

謝謝詹姆斯提出的問題。顯然，我們不能從手臂的角度來看這些。這是一項盲法研究。我們無法以這種方式查看數據。這是我們可以討論的混合事件發生率，目前我們還沒有了解藥物整體概況的具體細節。

Thanks, Samit. Let's move to the next question.

謝謝，薩米特。讓我們進入下一個問題。

Olivia Brayer, Cantor.

奧利維亞·布雷爾，坎托。

Hi, good morning. Thank you for the question. Can you guys talk through what you're looking to see in that adjunctive because for any data set next year? And when you think about uptake in that setting, are you getting any early feedback around potential off-label use from potential early adopters?

嗨，早安。謝謝你的提問。你們能談談你們希望在明年的任何數據集中看到什麼嗎？當您考慮在這種情況下的採用時，您是否從潛在的早期採用者那裡獲得了有關潛在的標籤外使用的任何早期回饋？

I mean how big of a market do you think that could realistically be just given the focus on making monotherapy use a standard of care. Also, I just wanted to ask a quick clarification on milvexian timelines. I know it's still 2027, but should we assume that it's later in the year considering today's update? Thank you.

我的意思是，您認為只要專注於使單一療法成為護理標準，實際上可以有多大的市場。另外，我只是想快速澄清米爾維西安的時間表。我知道現在還是 2027 年，但考慮到今天的更新，我們是否應該假設現在是今年稍後？謝謝。

Thanks for the questions, Olivia. Maybe we'll ask Samit and Adam to get those questions between the three of them.

謝謝你的提問，奧莉維亞。也許我們會請薩米特和亞當來解答他們三人之間的問題。

Yes. Thank you. Remember, Olivia, how patients are treated today. with the antipsychotics that are available without even having an approval in the label, patients are being treated with combinations of D2 agonist in this space. So it was important from our perspective to generate the data to showcase efficacy as well as the safety profile of combining muscularis with the background therapies that patients are on.

是的。謝謝。記住，奧莉維亞，今天的病人是如何治療的。由於抗精神病藥物甚至未經標籤批准，患者正在接受 D2 激動劑組合治療。因此，從我們的角度來看，產生數據來展示肌層與患者所接受的背景療法相結合的療效和安全性非常重要。

And that's the intent of showing the -- from the ARISE program perspective as an adjunctive therapy, what Coventry can deliver on top of the background therapies. That will be important, and that study will read out in 2025. On milvexian side, from a clarification perspective, the 2027 is an event-driven end point in the trial.

這就是從 ARISE 計畫作為輔助治療的角度來看，考文垂在背景治療的基礎上可以提供什麼的目的。這很重要，該研究將於 2025 年宣讀。

So we can't give you a specific in terms of the timing within 2027. That's why we give you a general guidance for 2027 as before.

因此，我們無法為您提供 2027 年內的具體時間安排。

Olivia, thanks. As it relates to adjunctive commercially today, use to two D2s to get greater efficacy and around 20% to 30% of the patients, even though the D2s are not FDA approved for adjunctive treatment, we do believe that could be an important adjunctive treatment option. Samit talked about the ARISE study, and we're working to generate evidence on this.

奧利維亞，謝謝。由於它與當今的商業輔助治療有關，使用兩種D2 可以獲得更大的療效，並且大約20% 至30% 的患者使用D2，儘管D2 尚未獲得FDA 批准用於輔助治療，但我們確實相信這可能是重要的輔助治療選擇。 Samit 談到了 ARISE 研究，我們正在努力尋找這方面的證據。

And pharmacologically, it makes sense adding an M1 and four on top of a D2 because, again, we think there could be synergistic effects there. So we're excited to see the study readout. Just to be clear, though, our teams are focused on driving on-label use in schizophrenia to make fee standard of care there.

從藥理學角度來看，在 D2 的基礎上添加 M1 和 4 個是有意義的，因為我們再次認為這可能會產生協同效應。因此，我們很高興看到研究結果。不過，需要明確的是，我們的團隊專注於推動精神分裂症的標籤使用，以使那裡的護理收費標準。

And we can't -- it's not going to be our choice, but patients may or may not choose to use COBENFY off-label because of the safety profile of the product. But we're really excited for the data readout next year in Juno schizophrenia as well as some of the other data readout that Samit talked about how phymerpsychosis, these are going to be important accelerators of growth for this product.

我們不能－這不會是我們的選擇，但由於該產品的安全性，患者可能會也可能不會選擇在標籤外使用 COBENFY。但我們對明年朱諾精神分裂症的數據讀出以及薩米特談到的精神分裂症的其他一些數據讀出感到非常興奮，這些將成為該產品增長的重要加速器。

And I would just remind you what Adam ended on is really important, which is that -- this is a product that, obviously, we're super excited about the initial indication in schizophrenia. We've got the adjunctive data coming, but this is a product that will continue to generate new line extensions with a very robust clinical development plan that we put in place for it.

我只想提醒你，亞當最後得出的結論非常重要，那就是——顯然，我們對這款產品在精神分裂症中的初步適應症感到非常興奮。我們已經收到了輔助數據，但這個產品將繼續產生新的產品線擴展，我們為此制定了非常強大的臨床開發計劃。

Great, thanks. Let's move to the next question, please.

太好了，謝謝。請讓我們進入下一個問題。

Sean McCutcheon, Raymond James.

肖恩麥卡琴，雷蒙德詹姆斯。

Hi, guys. Thanks for taking the question. One more on COBENFY. Can you speak to your view on the import of the M1 component for as it relates to potentially driving targeted improvements in particular, what proportion of the population have cognitive deficits. Do you expect these patients to be kind of parsed out in the monotherapy setting or post atypical or in the setting?

嗨，大家好。感謝您提出問題。再來一篇關於 COBENFY 的文章。您能否談談您對 M1 成分導入的看法，因為它與潛在推動有針對性的改善有關，特別是有認知缺陷的人口比例。您是否期望這些患者在單一治療環境中或在非典型治療環境中得到某種程度的解析？

And what are your comments to those that are looking at the BID regimen and GI adverse effects as potential barriers on ease of use in this patient population where compliance or lack thereof is a significant variable when thinking about your competitors that are coming up behind you? Thanks.

對於那些將BID 方案和胃腸道不良反應視為在該患者群體中使用的潛在障礙的人，您有何評論？變數？謝謝。

Good morning, Sean. Samit will take the first part and then Adam.

早安，肖恩。薩米特將擔任第一部分，然後是亞當。

Yes. Thank you. Remember, the differentiating feature for Covent is that it's a dual direct agonist as opposed to some of the other therapies in development that target the M4 to indirect ways because they are allosteric modulators, which require a ligand such as to be present in the brain.

是的。謝謝。請記住，Covent 的與眾不同之處在於，它是一種雙重直接激動劑，而不是其他一些正在開發的以間接方式靶向M4 的療法，因為它們是變構調節劑，需要配體，例如存在於大腦中的配體。

And M1 is a very important component because from a biological perspective, that is associated with cognition function in the brain. And so having a direct impact on M1 as well as M4 gives us that opportunity to really impact the cognition -- and during the overall life cycle, as we think about the Alzheimer's disease patients as they go through it, cognition does become important in terms of the impact on the patient and patient life and quality of life.

M1 是一個非常重要的組成部分，因為從生物學角度來看，它與大腦的認知功能有關。因此，對 M1 和 M4 產生直接影響使我們有機會真正影響認知——在整個生命週期中，當我們考慮阿茲海默症患者時，認知確實變得非常重要對患者以及患者生活和生活品質的影響。

So there's a large proportion of patients who will have cognitive impairment and will be eligible if the data reads out positive to be treated with the drug. So overall, that's why we've developed a program in all three parts of AD that impact from a psychosis perspective, agitation perspective as well as recognition perspective. Adam?

因此，很大一部分患者患有認知障礙，如果數據顯示呈陽性，則有資格接受該藥物治療。總的來說，這就是為什麼我們在AD的所有三個部分都發展了一個項目，從精神病的角度、激動的角度以及認知的角度產生影響。亞當？

Yes. So it relates to the dosing regimen for that step back and just talk about the leading cause of discontinuation. Number one is efficacy and COBENFY delivers unsurpassed efficacy, efficacy that's at least as good as a -- and the other areas of high-level discontinuation include areas like weight gain, include dysfunction, trouble concentrating, excessive sedation. And so now physicians don't need to trade that off. People living with schizophrenia commonly managed multiple medications at significantly higher rates than the general population.

是的。因此，這與退後一步的給藥方案有關，僅談談停藥的主要原因。第一個是功效，COBENFY 提供了無與倫比的功效，功效至少與高水平停藥的其他領域一樣好，包括體重增加、功能障礙、注意力不集中、過度鎮靜等領域。所以現在醫生不需要權衡這一點。精神分裂症患者通常使用多種藥物治療的比例明顯高於一般人。

In fact, when you look at patients with schizophrenia, they're on average seven pills a day which includes our antipsychotic. It could include different psychotropic medications, including anti-depressants, anti-anxiety medications as well as medicines to combat the adverse events of their existing products. So yes, we're going to need to manage this, but we don't believe that this will impact uptake based on the unprecedented efficacy that has shown.

事實上，當您觀察精神分裂症患者時，您會發現他們平均每天服用七片藥物，其中包括我們的抗精神病藥物。它可能包括不同的精神藥物，包括抗憂鬱藥物、抗焦慮藥物以及對抗現有產品不良事件的藥物。所以，是的，我們需要對此進行管理，但基於已顯示的前所未有的功效，我們認為這不會影響採用率。

Last thing I'd mention is we saw very low discontinuation rates in our clinical trial due to the fact that patients that robust efficacy that the product is well tolerated and we will provide support to both patients and caregivers to maximize compliance with this medicine.

我要提到的最後一件事是，我們在臨床試驗中看到非常低的停藥率，因為患者對該產品的強大療效具有良好的耐受性，我們將為患者和護理人員提供支持，以最大限度地提高對該藥物的依從性。

Thanks, Adam. I know you all have a busy morning in the space, so we'll take our last question. And then we'll turn it to Chris for some brief closing remarks.

謝謝，亞當。我知道你們在這個空間度過了一個忙碌的早晨，所以我們將回答最後一個問題。然後我們將請克里斯做一些簡短的結束語。

Kripa Devarakonda, Truist Securities.

Kripa Devarakonda，Truist 證券公司。

Hey, guys. Thank you so much for taking my question, and congrats on the quarter today. I'll switch gears and not ask a question. I want to ask a question about your test program. You've recently published data from a Phase 2 with mavacamten.

嘿，夥計們。非常感謝您提出我的問題，並祝賀今天這個季度。我會換個方向，不再問問題。我想問一個關於你們的測試程序的問題。您最近使用 mavacamten 發布了第 2 階段的資料。

Can you talk about how this translates to two to 4, which I think is the drug you've indicated as the PPAP drug? And what percentage -- like how big of a market do you see? And can you remind us of the time lines for this program? Thank you.

您能否談談這如何轉化為 2 到 4，我認為這就是您指定為 PPAP 藥物的藥物？您認為市場有多大？您能否提醒我們該計劃的時間表？謝謝。

Thank you, Kripa, for the question. HFpEF is an important indication. We've always indicated that as we think about myosin cardiac inhibitors, with the impact that it does have on the cardiac function and remodeling in general, there is an important element that we wanted to test out, which we first tested out with mavacamten in a small number of patients, which gave us an inkling into the -- through the biomarker work that we did over there through NT-proBNP as well as on measurement, which gives us confidence to continue with that program.

謝謝克里帕提出的問題。 HFpEF 是一個重要的指標。我們一直表示，當我們考慮肌球蛋白心臟抑制劑時，考慮到它對心臟功能和整體重塑的影響，我們想要測試一個重要的元素，我們首先用 mavacamten 進行了測試少數患者，這讓我們透過NT-proBNP 所做的生物標記工作以及測量得到了初步了解，這讓我們有信心繼續該計劃。

We switched over to MYK-224, which was the second program that was available to us, and that's the beauty of having two cardiac myosin inhibitors in the programs. And -- that trial is enrolling very well. We are now extending that trial in terms of the Phase 2a study to enroll more patients to generate the data.

我們改用了 MYK-224，這是我們可以使用的第二個程序，這就是程序中包含兩種心肌肌球蛋白抑制劑的好處。而且——該試驗的招募情況非常好。我們現在正在 2a 期研究方面擴展該試驗，以招募更多患者來產生數據。

We anticipate that, that Phase 2 data readout in the next couple of years and then start the Phase 3 program based on the doses that we have identified in that Phase 2 program. And then in the early part of next decade is when we anticipate to really have the Phase 3s reading out. We don't have a time line specifically in terms of the year -- but really excited to see what we have seen thus far and looking forward to initiation.

我們預計，第二階段的數據將在未來幾年內讀出，然後根據我們在第二階段計劃中確定的劑量啟動第三階段計劃。然後在下一個十年初期，我們預計將真正完成第三階段的宣讀。我們沒有具體的年份時間表，但很高興看到迄今為止我們所看到的，並期待著啟動。

Yes. As far as the opportunity, this is a large opportunity where heat affects around three million people in the United States and that is expected to grow significantly over the course of the decade. In fact, the heart failure drugs, the category is valued at over $12 billion in 2022, and we expect this to almost double by 2032. So this is a significant opportunity, and we're really pleased with what we're seeing early on with.

是的。就機會而言，這是一個巨大的機會，高溫影響了美國約 300 萬人，並且預計在十年內將顯著增長。事實上，心臟衰竭藥物這一類別的價值到2022 年將超過120 億美元，我們預計到2032 年這一數字將幾乎翻倍。滿意和。

Thanks, Adam. Well, thanks, everyone, for joining us for the call today and for the very thoughtful questions. Maybe I'll just leave you with a few thoughts on the performance for the quarter.

謝謝，亞當。好的，謝謝大家今天加入我們的電話會議並提出非常深思熟慮的問題。也許我會留給您一些關於本季業績的想法。

First, as you hopefully have gotten from the discussion, we remain very focused on execution. The growth portfolio is now, as David mentioned, contributing nearly half of our total revenue -- and that profile continues to benefit from robust demand for key products, products like Reblozyl, Breyanzi, and Opdualag.

首先，正如您希望從討論中了解到的那樣，我們仍然非常注重執行。正如 David 所提到的，成長型產品組合現在貢獻了我們總收入的近一半，而這一狀況繼續受益於對 Reblozyl、Breyanzi 和 Opdualag 等關鍵產品的強勁需求。

Second, the COBENFY approval is a pivotal achievement. We've been working hard to deliver that since we closed the Karuna transaction. And this is an important medicine for patients, and it's an important growth driver for the portfolio.

其次，COBENFY 的批准是一項關鍵成就。自從我們完成卡魯納交易以來，我們一直在努力實現這一目標。這對患者來說是一種重要的藥物，也是該產品組合的重要成長動力。

Third, we continue to advance our innovative pipeline across therapeutic areas. We've had several important readouts over the course of the year, and we have a few more coming between now and the end of the year as well as beginning of next year.

第三，我們持續推動跨治療領域的創新管道。在這一年中，我們已經發布了一些重要的數據，從現在到年底以及明年初，我們將發布更多數據。

And then finally, again, as you hopefully gathered, our commitment to operational excellence is yielding results, and we're going to remain focused on driving value across the organization. So thanks again for your time today. And as always, the team is available for follow-up questions, and have a great rest of the day.

最後，正如您所希望的那樣，我們對卓越營運的承諾正在產生成果，我們將繼續專注於推動整個組織的價值。再次感謝您今天抽出時間。像往常一樣，團隊可以回答後續問題，並度過愉快的一天。

The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.

會議現已結束。感謝您參加今天的演講。您現在可以斷開連線。