Novartis AG (NVS) 2024 Q1 法說會逐字稿

Good morning and good afternoon, and welcome to the Novartis Q1 2024 Results Release Conference Call and live webcast. (Operator Instructions) The conference is being recorded. (Operator Instructions) A recording of the conference call, including the Q&A session, will be available on our website shortly after the call ends.

早上好，下午好，歡迎來到諾華 2024 年第一季業績發布電話會議和網路直播。 （操作員指示）會議正在錄音。 （操作員說明）電話會議的錄音（包括問答環節）將在通話結束後不久在我們的網站上提供。

With that, I would like to hand over to Ms. Sloan Simpson, Head of Investor Relations. Please go ahead, Madam.

接下來，我想將會議交給投資人關係主管 Sloan Simpson 女士。請繼續，女士。

Thank you so much, operator. Good morning, and good afternoon, everyone. Thank you for joining our first quarter 2024 earnings call. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. For a description of some of these factors, please refer to the company's Form 20-F and its most recent quarterly results on Form 6-K that respectively were filed with and furnished to the U.S. Securities and Exchange Commission.

非常感謝你，接線生。大家早安，下午好。感謝您參加我們的 2024 年第一季財報電話會議。今天提供的資訊包含前瞻性陳述，涉及已知和未知的風險、不確定性和其他因素。這些可能導致實際結果與此類陳述明示或暗示的任何未來結果、績效或成就有重大差異。有關其中一些因素的描述，請參閱該公司分別向美國證券交易委員會提交和提供的 20-F 表和 6-K 表中的最新季度業績。

And with that, I will hand across to Vas.

接下來，我將把工作交給瓦斯。

Thank you, Sloan. I'd like to open today's call by first thanking Samir Shah for his incredible tenure as our Head of Investor Relations for over a decade. We're grateful for all of his contributions. We look forward to his continued contributions in the new role at Novartis. And I want to welcome Sloan Simpson, I think Sloan will do an absolutely outstanding job serving all of you as our Head of Investor Relations. I've worked with her for many, many years. I think we're really pleased and grateful to have her on board.

謝謝你，斯隆。在今天的電話會議開始時，我首先要感謝薩米爾·沙阿 (Samir Shah) 十多年來擔任我們投資者關係主管的出色任期。我們感謝他的所有貢獻。我們期待他在諾華的新職位上繼續做出貢獻。我想歡迎斯隆辛普森 (Sloan Simpson)，我認為作為我們的投資者關係主管，斯隆將出色地為大家服務。我和她一起工作了很多很多年。我想我們真的很高興也很感激她的加入。

So let's turn to the quarter. Novartis delivered a really strong start to the year with double-digit sales growth, core margin expansion, which enabled us to upgrade our guidance, and Harry will go through the guidance in more detail. Sales were up 11% in constant currency. Core operating income was up 22%. Our core margin reached 38.4% as we steadily march to our goal of 40% plus by 2027.

那麼讓我們轉向本季。諾華公司以兩位數的銷售額成長和核心利潤率擴張，在今年取得了非常強勁的開局，這使我們能夠升級我們的指導意見，哈利將更詳細地介紹該指導意見。以固定匯率計算，銷售額成長了 11%。核心營業收入成長 22%。我們的核心利潤率達到 38.4%，穩步向 2027 年 40% 以上的目標邁進。

In addition, we had a number of important innovation milestones in the quarter, which I'll go through over the course of the call. But a few I'd want to particularly highlight, the Fabhalta positive opinion enables us to launch Fabhalta in Europe. Scemblix first-line readout, we think will be very important for a major medicine for the company. And we also had the updated PSMAfore OS results, which will enable us now to move forward with the filing of Pluvicto in the United States.

此外，我們在本季實現了許多重要的創新里程碑，我將在電話會議中介紹這些里程碑。但我想特別強調的是，Fabhalta 的積極意見使我們能夠在歐洲推出 Fabhalta。我們認為 Scemblix 第一線讀數對於公司的主要藥品來說非常重要。我們還獲得了更新的 PSMAfore OS 結果，這將使我們現在能夠推進 Pluvicto 在美國的申請。

Now moving to Slide 5. Now our growth in the quarter was broad-based, and we had strong contributions from many of our key growth drivers, including Entresto, Kesimpta, Cosentyx, which had a very strong quarter as well as Kisqali. I would also say geographically, our performance was broad-based with strong growth across U.S., Europe, China with very strong growth and Japan.

現在轉到幻燈片 5。我還想說，從地理來看，我們的業績基礎廣泛，在美國、歐洲、中國和日本都有強勁成長。

As you can see on the chart, the strong growth was indicated by 41% constant currency growth, and we expect this growth to continue over the course of the year, which is what gives us confidence to do the upgraded guidance that we've outlined this morning.

正如您在圖表中看到的那樣，41％的恆定貨幣增長率表明了強勁的增長，我們預計這種增長將在今年持續下去，這讓我們有信心執行我們概述的升級指導今天早上。

Now moving to Slide 6, and we'll walk through the brands 1 by 1 as we always do. First, with Entresto, we had double-digit growth, up 36% in quarter 1. That was, again, geographically broad-based, U.S. and ex-U.S. In the U.S., our weekly TRx continue to reach new highs. We had 38% constant currency growth outside of the U.S. And we continue to see momentum for this brand. We're in a strong guideline position both in the U.S. and in Europe. We have further penetration opportunities in heart failure globally and specifically in hypertension in China, in Japan and in Japan, we have protection into the early 2030s with this medicine.

現在轉到幻燈片 6，我們將像往常一樣一一介紹品牌。首先，Entresto 實現了兩位數的成長，第一季成長了 36%。在美國，我們的每週 TRx 繼續創下新高。我們在美國以外的地區實現了 38% 的持續貨幣成長，並且我們繼續看到該品牌的發展勢頭。我們在美國和歐洲都處於強而有力的指導地位。我們在全球心臟衰竭方面有進一步滲透的機會，特別是在中國和日本的高血壓方面，我們在 2030 年代初期可以用這種藥物提供保護。

For forecasting purposes, no change in our Entresto LoE outlook, continue to guide to a mid-2025 LoE while continuing to aggressively defend our various patents. And then in terms of the EU, we continue to guide to RDP in November 2026 benefiting from our pediatric extension.

出於預測目的，我們的 Entresto LoE 前景沒有變化，繼續指導 2025 年中期 LoE，同時繼續積極捍衛我們的各種專利。然後就歐盟而言，我們將繼續指導 2026 年 11 月的 RDP，受益於我們的兒科擴展。

Now moving to Slide 7. Cosentyx grew 25% in the quarter, and I think really got back to the dynamic growth we expect for this medicine. This was fueled both by our core indications, but also some strong launches, and I'll go through that in a bit more detail. U.S. was up 25% in constant currency, ex-U.S., 24%. We had highly -- we're highly competitive in our core indications. And so we saw a return to market share improvement in psoriasis and in the rheumatology indications both in the U.S. and in Europe. And we're now the leading originator biologic in the IL-17 class in EU and China.

現在轉到幻燈片 7。這既是由我們的核心指標推動的，也是由一些強勁的發布推動的，我將更詳細地介紹這一點。以固定匯率計算，美國上漲 25%，不包括美國則上漲 24%。我們在核心適應症方面具有很強的競爭力。因此，我們看到美國和歐洲牛皮癬和風濕病適應症的市佔率有所回升。我們現在是歐盟和中國 IL-17 類生物製劑的領先創始者。

Now in terms of our new launches, we saw very strong performance in HS, hidradenitis suppurativa, where we have over 50% now NBRx share versus adalimumab in U.S. and Germany. When we compare our launch on a comparable basis to the adalimumab launch in this indication, we currently see ourselves at nearly 3x the performance of that previous launch. I think really highlighting how strong the uptake for Cosentyx has been in this new indication.

現在就我們的新產品而言，我們在 HS、化膿性汗腺炎方面看到了非常強勁的表現，在美國和德國，與阿達木單抗相比，我們目前 NBRx 的市佔率超過 50%。當我們在可比較的基礎上將我們的發布與阿達木單抗在該適應症中的發布進行比較時，我們目前認為我們的性能是之前發布的近 3 倍。我認為真正強調了 Cosentyx 在這一新適應症中的接受程度有多強烈。

We also had very strong performance in the intravenous indication ahead of the J-code, which we expect in July. I think, again, that indicates there is strong interest in having an IV option for patients with Cosentyx in the rheumatology indications. So we'll look forward to further acceleration in the back half of the year once we have that J-code in place.

我們在 J 代碼之前的靜脈注射適應症方面也取得了非常強勁的表現，我們預計將在 7 月推出 J 代碼。我認為，這再次表明人們對風濕病適應症患者採用 Cosentyx 靜脈注射有濃厚的興趣。因此，一旦 J 代碼就位，我們將期待在今年下半年進一步加速。

Now moving to Slide 8. Kesimpta delivered 66% growth on the quarter, and this was again global U.S. and ex-U.S. driven. We have over 100,000 patients treated worldwide on the medicine, and the majority of these patients are either naive or first switch, which reflects the strategy we have for this brand.

現在轉到幻燈片 8。驅動的。我們在全球範圍內有超過 10 萬名患者接受該藥物治療，其中大多數患者要么是初次使用該藥物，要么是首次使用該藥物，這反映了我們對該品牌的策略。

In the U.S., we saw a very strong demand-driven growth with NBRx volume at plus 26% versus prior quarter. And one of our key priorities now in the U.S. is to increase our B-cell market share over the coming quarters. Outside of the U.S., we have leadership now in 7 out of 10 major markets, and we look forward to continuing to drive the convenience and high efficacy story that Kesimpta presents in these markets.

在美國，我們看到需求驅動的成長非常強勁，NBRx 銷量比上一季成長了 26%。我們現在在美國的首要任務之一是在未來幾季增加我們的 B 細胞市場份額。在美國以外，我們目前在十分之七的主要市場中處於領先地位，我們期待繼續推動 Kesimpta 在這些市場中呈現的便利性和高效性。

In the quarter as well, we announced the ALITHIOS 6-year long-term data, which demonstrated sustained efficacy and the consistent safety profile for Kesimpta. In this study, 9 out of 10 patients were free on the NEDA-3 score of disease activity. And we also saw treatment-naive patients derive substantial benefits across multiple markers of disease activity. So even in the face of some competitor launches, we feel very confident about the 1 minute a month self-administered dosing, high efficacy, strong safety profile of Kesimpta.

在本季度，我們也公佈了 ALITHIOS 6 年長期數據，證明了 Kesimpta 的持續療效和一致的安全性。在這項研究中，10 名患者中有 9 名的疾病活動度 NEDA-3 評分沒有問題。我們也看到未經治療的患者在多種疾病活動標記方面獲得了實質的益處。因此，即使面對一些競爭對手的上市，我們對 Kesimpta 每月 1 分鐘自行給藥、高效、安全的特性非常有信心。

Now moving to Slide 9. Kisqali grew 54% in metastatic breast cancer with now continued leading share in new patient starts. U.S. was up 72%. And I think there's increasing recognition of the unique profile that Kisqali offers given its broad data set of OS across 3 different studies in metastatic breast cancer. We have leading NBRx share at 45%. And we see a steady growth in writers. We're also working to increase depth as well as improve our market access position across key accounts ahead of the early breast cancer launch.

現在轉到幻燈片 9。美國上漲72%。我認為，鑑於 Kisqali 在 3 項不同的轉移性乳癌研究中提供的廣泛 OS 資料集，人們越來越認識到其獨特的概況。我們擁有 45% 的領先 NBRx 份額。我們看到作家的數量正在穩步增長。在早期乳癌推出之前，我們也致力於增加深度並改善我們在關鍵客戶中的市場准入地位。

Now outside of the United States, 39% growth. We're the fastest-growing CDK4/6 in Europe and a market leader in the pre-menopausal indication. We also successfully entered the NRDL list in China in quarter 1, and it's early days in China, but given the strength of our China operations, we're hopeful we can draw dynamic growth for Kisqali in China over time. The regulatory review in early breast cancer is ongoing. We're filed in the U.S. and EU and currently expect regulatory review to proceed as planned.

現在美國以外的地區成長了 39%。我們是歐洲成長最快的 CDK4/6，也是停經前適應症的市場領導者。我們還在第一季成功進入了中國的國家醫保目錄，目前在中國還處於早期階段，但鑑於我們在中國業務的實力，我們希望隨著時間的推移，我們能夠為Kisqali 在中國帶來強勁的增長。早期乳癌的監管審查正在進行中。我們已在美國和歐盟提交申請，目前預計監管審查將按計劃進行。

Our manufacturing adjustments, which we disclosed a few weeks ago are on track to ensure alignment with the latest regulatory standards in early breast cancer by the end of Q2, and we continue to expect to be able to launch this medicine in the second half of this year.

我們幾週前披露的生產調整預計將確保在第二季末符合早期乳癌的最新監管標準，我們仍然期望能夠在今年下半年推出該藥物年。

Now moving to Slide 10. Pluvicto had strong growth of 47% in the quarter, driven by new patient starts and very early beginnings of growth as well outside of the U.S. We have 400 treatment sites now up and running in the U.S., on a steady progress to our goal to get well over 500 sites fully certified for the use of Pluvicto. Also, our supply performance is now consistently at a very high level with over 99.5% of injections administered on the planned day. So ample supply, Indianapolis facility up and running, continued expansion of our manufacturing network. So we really feel like we're now in a position to fully supply the market consistently globally for this medicine.

現在轉到幻燈片 10。目標正在取得進展，即讓超過500 個站點獲得使用Pluvicto 的全面認證。此外，我們的供應績效目前一直處於非常高的水平，超過 99.5% 的注射是在計劃日進行的。供應充足，印第安納波利斯工廠投入運行，我們的製造網路持續擴張。因此，我們確實覺得我們現在能夠在全球範圍內持續全面供應這種藥物的市場。

Now over the course of 2024, we're going to focus on share expansion within existing sites and particularly expanding the referral network of medical oncologists who can refer into a Pluvicto-treating center, we feel like this will be the key now in the post-taxane setting. We also want to build our business outside of the United States with some important launches in Europe as we also build towards launches -- planned launches in Japan and China, both countries where we have planned new manufacturing facilities to support the Pluvicto and Lutathera business.

現在，在 2024 年，我們將重點關注現有站點內的份額擴張，特別是擴大可以轉診至 Pluvicto 治療中心的腫瘤內科醫生的轉診網絡，我們認為這將是現在的關鍵-紫杉烷設置。我們也希望在美國以外建立我們的業務，在歐洲推出一些重要產品，同時我們也計劃在日本和中國推出產品，我們在這兩個國家都計劃了新的製造設施來支持 Pluvicto 和 Lutathera 業務。

Our existing indications are also on track. We announced earlier this quarter that the PSMAfore submission-enabling OS readout was achieved. And this will put us in a position to file Pluvicto early in the second half, so a midyear filing for this medicine. And then PSMAddition also on track as well as the PSMA delayed castration localized oligometastatic program as well.

我們現有的跡像也已步入正軌。我們在本季稍早宣布，已實現支援 PSMAfore 提交的作業系統讀出。這將使我們能夠在下半年早些時候提交 Pluvicto 申請，即年中提交該藥物的申請。然後 PSMAddition 以及 PSMA 延遲去勢局部寡轉移計畫也步入正軌。

Now a little more detail on the PSMAfore submission-enabling OS readout. We had a primary endpoint that we read out last year where we met the primary endpoints as well as really strong data across all of the secondary and exploratory endpoints, a very impressive relative risk reduction for rPFS, strong profile across the patient-reported outcomes as well as the various response, ORR, DCR, and DOR. What we announced earlier in the quarter was the updated third interim, which gave us a higher proportion of OS events. The OS hazard ratio was less than 1, which puts us in a position to file midyear.

現在詳細介紹一下支援 PSMAfore 提交的作業系統讀數。我們去年讀出了一個主要終點，我們達到了主要終點，以及所有次要和探索性終點的非常強大的數據，rPFS 的相對風險降低非常令人印象深刻，患者報告的結果的強大特徵以及各種響應、ORR、DCR 和DOR。我們在本季早些時候宣布的是更新的第三個中期報告，這為我們提供了更高比例的作業系統事件。作業系統風險比小於 1，這使我們能夠在年中提交報告。

And other secondary endpoints were consistent with the previous results as was the rPFS. And what we feel and see is with the additional 8 months of follow-up, we have high confidence in the safety profile of Pluvicto. And so these results will be presented at an upcoming medical congress. And of course, we're working as quickly as we can to get this filed in.

其他次要終點與先前的結果一致，rPFS 也是如此。我們感受到和看到的是，透過額外 8 個月的隨訪，我們對 Pluvicto 的安全性充滿信心。因此，這些結果將在即將召開的醫學大會上公佈。當然，我們正在盡快將其歸檔。

Now moving to Slide 12. Leqvio also had a really strong quarter. Adoption expanded steadily in the U.S., but also outside of the United States, as you can see here, on the left-hand chart, very strong performance, both in the U.S. and outside the U.S. Taking the U.S. first, we had growth outpacing the advanced lipid-lowering market. We have now nearly 3,900 facilities that are ordering Leqvio, increased breadth and depth across our key accounts. We continue to see buy and bill as the key driver overall of the business. But we do see also the use of other channels as well.

現在轉到投影片 12。在美國和美國以外的地區，採用率穩步擴大，正如您在左側圖表中看到的那樣，無論是在美國還是在美國以外的地區，其表現都非常強勁。成長速度超過了美國先進的降脂市場。目前，我們有近 3,900 家工廠正在訂購 Leqvio，這增加了我們主要客戶的廣度和深度。我們仍然將購買和計費視為整體業務的關鍵驅動力。但我們也確實看到了其他管道的使用。

Outside of the U.S., we have a consistent rollout. Now we have 29 countries where Leqvio is publicly reimbursed and an additional 39 with private commercial coverage. This puts us in a strong position with our top 3 European markets contributing 50% of international sales, but really strong growth across the international region. And strong early uptake in China in the self-pay setting with over 200 new patients a day ahead of our planned NRDL listing in the first half -- first part of next year.

在美國以外，我們持續推出。現在，我們有 29 個國家提供 Leqvio 公開報銷，另外 39 個國家提供私人商業保險。這使我們處於有利地位，我們的三大歐洲市場貢獻了國際銷售額的 50%，而且整個國際地區的成長確實強勁。在中國，自費醫療的早期普及率很高，在我們計劃於上半年（即明年上半年）列入國家醫療保健目錄之前，每天新增患者超過 200 名。

Lastly, we had new data at ACC and a publication as well, which supported the early initiation of Leqvio, demonstrating that starting Leqvio early in patients requiring secondary prevention for a cardiovascular event, a lot of these patients do achieve their LDL-C goals earlier.

最後，我們在ACC 和一份出版物中獲得了新數據，支持早期開始使用Leqvio，表明在需要心血管事件二級預防的患者中儘早開始使用Leqvio，其中許多患者確實更早地實現了LDL- C 目標。

Now moving to the next slide, Slide 14. Scemblix, grew 83% in the quarter again, primarily driven by the third-line indication with our first-line submission on track to be completed in the coming months. We had continued momentum in the core third-line indication, over 40% NBRx share. Outside of the U.S., we're at a 32% total market share driven by our key markets, Japan, France and Germany. And here in the third-line setting, we primarily focus on early identification of patients who could benefit from a switch to Scemblix post 2 TKIs.

現在轉到下一張投影片，即投影片 14。我們在核心三線適應症方面繼續保持勢頭，NBRx 份額超過 40%。在美國以外的市場，我們的總市佔率為 32%，主要市場包括日本、法國和德國。在三線環境中，我們主要關注早期識別可以從 2 次 TKI 後改用 Scemblix 中受益的患者。

As a reminder, our ASC4FIRST study enabled first-in-line submission -- first-line submission in half 1. Primary endpoints were met versus all standard of care TKIs and versus Gleevec as well, favorable safety and tolerability profile, and we can confirm that the full data will be presented at ASCO in 2024.

提醒一下，我們的 ASC4FIRST 研究實現了一線提交——一線提交減半 1。將於2024 年在ASCO 上公佈。

Now turning to Fabhalta. We're at the early stages of the PNH launch, and we didn't expect really to see significant sales at this very early stage, given the complexity of this launch. But we are very pleased with the early launch indicators, we've had a rapid increase in the number of HCPs who are certified under the REMS program, an increase in new writers and patient starts, which are exceeding our internal expectations, we see uptake across naive and switch patients for this medicine.

現在轉向 Fabhalta。我們正處於 PNH 發布的早期階段，考慮到此次發布的複雜性，我們並沒有期望在這個非常早期的階段真正看到顯著的銷量。但我們對早期啟動指標感到非常滿意，通過 REMS 計劃認證的 HCP 數量迅速增加，新作者和患者開始增加，這超出了我們的內部預期，我們看到了採用情況跨越初次使用這種藥物的患者和轉換患者。

And we also are really happy to see HCPs willing to work through the medical exception process to get patients on this medicine. So we've also have the positive CHMP opinion for PNH, and we expect that full approval to happen in the coming few months. And we'll consistently work to launch this medicine across the globe as well as drive rapid uptake in the United States.

我們也很高興看到 HCP 願意透過醫療例外流程讓病人接受這種藥物。因此，我們對 PNH 也有積極的 CHMP 意見，我們預計在未來幾個月內將獲得完全批准。我們將持續努力在全球推出這種藥物，並推動美國的快速普及。

Now turning to Slide 15. We also announced our Phase III APPLAUSE-IgAN study, full results earlier in the quarter, where we demonstrated 38% proteinuria reduction relative to placebo. In this study, we randomized patients to iptacopan versus placebo. The results we read out was the 9-month interim proteinuria analysis. These patients will be -- continue to be followed out to month 24 for the full eGFR analysis.

現在轉向幻燈片 15。在這項研究中，我們將患者隨機分配到伊普塔考潘組和安慰劑組。我們讀出的結果是 9 個月的中期蛋白尿分析。這些患者將繼續追蹤至第 24 個月，以進行完整的 eGFR 分析。

You can see on the right-hand panel, very impressive proteinuria reduction of 43.8% versus placebo at 9%, clinically meaningful and statistically significant. We know that complement activation is a key driver of inflammation in IgAN. And importantly, the overall safety profile was consistent with data we've previously reported. We've submitted this data to FDA. And just one clarification, we did not use a priority review voucher for this medicine. The FDA granted us priority review based on the data set that we provided. So this study continues as well for its eGFR readout in 2025, and we look forward to really getting a full approval very shortly -- or getting the initial approval in the coming period.

您可以在右側面板上看到，與安慰劑相比，蛋白尿降低了 43.8%，令人印象深刻，具有臨床意義和統計意義。我們知道補體活化是 IgAN 發炎的關鍵驅動因素。重要的是，整體安全狀況與我們先前報告的數據一致。我們已將此數據提交給 FDA。需要澄清的是，我們沒有對這種藥物使用優先審查券。 FDA 根據我們提供的數據集授予我們優先審查權。因此，這項研究也將在 2025 年繼續進行 eGFR 讀數，我們期待很快就能真正獲得全面批准，或在未來一段時間內獲得初步批准。

Moving to Slide 16. Now remibrutinib demonstrated -- had already demonstrated in an earlier study at 12 weeks, robust efficacy and safety. But we needed to wait for the 52-week data to be in a position to file in chronic spontaneous urticaria. And this data came out positive, enabling us now to move forward toward this important filing.

轉到幻燈片 16。但我們需要等待 52 週的數據才能歸檔慢性自發性蕁麻疹。這些數據的結果是正面的，使我們現在能夠朝著這項重要的申請邁進。

As a reminder, there's about 400,000 CSU patients in the U.S. not controlled or refractory to antihistamines. And only less than 20% of these patients are currently on biologics. So there's a large opportunity for a high-efficacy oral medicine. The previous primary endpoint data at week 12 as shown here, where we very consistently showed improvements versus placebo at the week 12 on the UAS7 score. And so we'll look forward to presenting the full data set in the second quarter for this medicine out to 52 weeks. And with the consistent favorable safety profile we've demonstrated with overall rates of AE comparable to placebo and balanced liver function test as well as the clear efficacy data, we'll look forward to global submissions in the second half of remibrutinib.

提醒一下，美國大約有 40 萬名 CSU 患者未得到控製或對抗組織胺藥物無效。這些患者中目前只有不到 20% 正在服用生物製劑。因此，高效口服藥物有很大的機會。先前第 12 週的主要終點數據如下所示，我們在第 12 週的 UAS7 評分上始終顯示出與安慰劑相比的改善。因此，我們期待在第二季度提供該藥物長達 52 週的完整數據集。憑藉我們已經證明的一致良好的安全性、與安慰劑和平衡肝功能測試相當的 AE 總體發生率以及明確的療效數據，我們將期待瑞米布替尼下半年的全球提交。

So all taken together, we're on track across our innovation goals for the year. I did want to highlight that we have shifted our iptacopan C3G U.S. submission to the second half. There is no great correlate for efficacy in C3G, given the ultra-rare nature of this disease. We provided the FDA our 6-month data. While certainly, we believe that 6-month data was very compelling. The FDA wanted to see the additional 6-month follow-up for these patients after all patients had rolled over on to active. The first 6-month period was randomized, second 6-month period, all patients are on active. So we will complete that 6-month follow-up and then file in the second half. And we remain very excited about the opportunity to bring Fabhalta as well to patients with C3G.

總而言之，我們正在實現今年的創新目標。我確實想強調，我們已將 iptacopan C3G 美國提交移至下半年。鑑於這種疾病極為罕見，因此 C3G 的療效沒有很大的相關性。我們向 FDA 提供了 6 個月的數據。當然，我們相信 6 個月的數據非常引人注目。 FDA 希望在所有患者轉為活躍狀態後對這些患者進行額外 6 個月的追蹤。在第一個 6 個月期間是隨機的，第二個 6 個月期間，所有患者都處於活躍狀態。因此，我們將完成 6 個月的跟進，然後在下半年歸檔。我們仍然對有機會將 Fabhalta 帶給 C3G 患者感到非常興奮。

So moving to the next slide. We also are on track for our range of submissions, '24, '25 and '26 to '28. So we'll continue to keep you abreast of how data sets unfold as well as potential readout timelines as we understand those readout timelines better and really excited about the catalyst-rich profile that we have out -- through the coming years.

現在轉到下一張投影片。我們也正在按計劃提交 '24、'25 和 '26 至 '28 的提交內容。因此，我們將繼續讓您了解資料集如何展開以及潛在的讀出時間線，因為我們更好地理解了這些讀出時間線，並且對我們在未來幾年中獲得的富含催化劑的資料感到非常興奮。

So moving to Slide 19, I'll hand it over to Harry.

現在轉到幻燈片 19，我將把它交給 Harry。

Yes. Thank you very much, Vas. Good morning, good afternoon, everyone. I'm now going to walk you through some of the financials for the first quarter. And as always, my comments refer to growth rates in constant currencies unless otherwise noted. Also, throughout the presentation, I refer to continuing operations. And as you see from the numbers, it has been a very strong start to the year.

是的。非常感謝你，瓦斯。大家早安，下午好。我現在將向您介紹第一季的一些財務數據。像往常一樣，除非另有說明，我的評論指的是按固定貨幣計算的增長率。此外，在整個演示中，我提到了持續經營。正如您從數字中看到的那樣，今年的開局非常強勁。

So on Slide 20, you see a summary of our financial performance with net sales up 11% and core operating income up 22%. Our core margin grew 340 basis points to reach 38.4%, showing that we are very well on track to achieve our midterm margin guidance of 40% plus by 2027. Core EPS was $1.80 for the first quarter, growing 23%, a bit ahead of (inaudible) through the share buyback program. Free cash flow was $2 billion, declining versus quarter 1 of 2023, but that was due to a prior year one-timer and the timing of some tax payments this year. However, and importantly, for the full year 2024, free cash flow is expected to grow approximately in line with core operating income. So in summary, very strong start to the year as our efforts to focus and streamline the business continue to pay off.

在投影片 20 上，您可以看到我們的財務表現摘要，淨銷售額成長 11%，核心營業收入成長 22%。我們的核心利潤率成長了340 個基點，達到38.4%，這表明我們正在順利實現到2027 年實現40% 以上的中期利潤率指導目標。略高於去年同期（聽不清楚）透過股票回購計畫。自由現金流為 20 億美元，較 2023 年第一季有所下降，但這是由於上一年的一次性現金流和今年部分納稅的時間安排所致。然而，重要的是，2024 年全年，自由現金流預計將大致與核心營業收入成長一致。總而言之，今年的開局非常強勁，我們專注於和簡化業務的努力不斷得到回報。

This brings us already to our full year guidance on Slide 21. So the strong momentum in our business across our in-market growth brands and launches, both in the U.S. and international markets give us the confidence to upgrade both top and bottom-line guidance. We have also a favorable update on generic entry assumptions in U.S., but that's actually a smaller element of the analysis driving our 2024 guidance upgrade. We now expect net sales to grow in the range of high single-digit to low double-digit and core operating income to grow in the range of low double-digit to mid-teens.

這讓我們已經看到了幻燈片 21 上的全年指導。我們也對美國的一般進入假設進行了有利的更新，但這實際上只是推動我們 2024 年指導升級的分析中的一個較小因素。我們現在預期淨銷售額將在高個位數到低兩位數的範圍內成長，核心營業收入將在低兩位數到中雙位數的範圍內成長。

Underpinning our guidance are 2 key assumptions that no Entresto and no Promacta generics will launch in 2024 in U.S. And to complete our '24 full year guidance, please know that we continue to expect core net financial expenses to be in the range of $0.6 billion to $0.7 billion. Our core tax rate to be around 16.5%.

支持我們指導的是兩個關鍵假設，即2024 年不會在美國推出Entresto 和Promacta 仿製藥。 6 億美元之間7億美元。我們的核心稅率約為16.5%。

Now moving to Slide 22. I'm very pleased with the quality of our quarter 1 sales growth driven by our key in-market brands, which grew as Vas showed also on the prior slide, 41% in the quarter. And the vast majority of these brands still have many years of patent protection ahead of them. So their continued momentum strongly supports our midterm growth outlook of 5% CAGR through 2028.

現在轉到投影片 22。而這些品牌中的絕大多數仍然有多年的專利保護。因此，他們的持續成長勢頭有力地支持了我們在 2028 年複合年增長率 5% 的中期成長前景。

Slide 23, please. Just to highlight that we continue our shareholder-friendly capital allocation strategy in quarter 1, of course, investing in the business alongside returning capital to shareholders. Notably, in Q1, we announced 2 value-creating bolt-ons in our core therapeutic areas, the proposed acquisition of MorphoSys and the licensing deal of Arvinas, both of which align with our strategic focus in oncology. In terms of returning capital to our shareholders, we paid $7.6 billion of our growing dividend in quarter 1. And we also continue our up to $15 billion share buyback program and we still have $11.7 billion remaining to be executed by the end of 2025.

請投影片 23。只是想強調一下，我們在第一季繼續實行有利於股東的資本配置策略，當然，在向股東返還資本的同時投資業務。值得注意的是，在第一季度，我們宣布了在核心治療領域的兩項創造價值的補充計劃，即擬議收購 MorphoSys 和 Arvinas 的許可協議，兩者都符合我們在腫瘤學方面的戰略重點。在向股東返還資本方面，我們在第一季支付了 76 億美元不斷增長的股息。 我們還繼續執行高達 150 億美元的股票回購計劃，到 2025 年底我們仍有 117 億美元需要執行。

Already to my final slide, 24, we have outlined some of the details regarding the FX impact. And as you see, in quarter 1, FX had a 1% negative impact on sales and 6 points negative on core operating income, the latter driven by the strong Swiss francs. And if late-April rates prevail, including the most recent strengthening of the U.S. dollar, we expect the full year impact of currency still to be less than it was in '23 on a top line negative 2%, bottom line, a negative 4%. As a reminder, as this is hard to forecast from the outside and moving all the time, we are updating our -- the expected FX impact on our website on a monthly basis. And with that, I hand back to Vas.

在我的最後一張投影片 24 中，我們已經概述了有關外匯影響的一些細節。正如您所看到的，在第一季度，外匯對銷售產生了 1% 的負面影響，對核心營業收入產生了 6 個百分點的負面影響，後者是由強勢瑞士法郎推動的。如果 4 月下旬的利率佔上風，包括最近美元走強，我們預計貨幣對全年的影響仍將小於 23 年，頂線負 2%，底線負 4%。提醒一下，由於這很難從外部預測並且一直在變化，因此我們每月都會在我們的網站上更新預期的外匯影響。說完，我把話交還給瓦斯。

Great. Thanks, Harry. So as you heard, a strong start to the year with double-digit sales growth, strong core margin expansion. And with the strong momentum we see in the business, we're able to raise our guidance for the year. We saw this momentum across all of our key growth brands and across geographies, I think, indicating the high quality of the performance that we're seeing in the company.

偉大的。謝謝，哈利。正如您所聽到的，今年開局強勁，銷售額實現兩位數成長，核心利潤率強勁擴張。憑藉我們在業務中看到的強勁勢頭，我們能夠提高今年的指導。我認為，我們在所有主要成長品牌和各個地區都看到了這種勢頭，這表明我們在公司看到了高品質的表現。

Our pipeline continues to advance with multiple submissions and submission-enabling readouts as we outlined. And we continue to have confidence in our midterm guidance of 5% constant currency sales growth, '23 to '28, and 40% plus core operating income margin by 2027.

正如我們所概述的，我們的管道繼續推進多次提交和支援提交的讀數。我們仍然對 23 年至 28 年期間 5% 的固定匯率銷售成長以及到 2027 年核心營業收入利潤率 40% 以上的中期指導充滿信心。

So with that, I'll hand it back to Sloan, who will outline some of our upcoming investor events.

因此，我將把它交還給斯隆，他將概述我們即將舉行的一些投資者活動。

Thank you, Vas. Before we open up for questions, I just wanted to flag a few investor events that we're planning to hold this year. First, we'll have an in-person event at ASCO in Chicago on June 2, highlighting Scemblix ASC4FIRST data, which Vas mentioned. We'll also have a virtual event on our renal pipeline in the second half of the year. and we'll be having our annual Meet Novartis Management event in London on November 20 to 21. We hope to see many of you at these events.

謝謝你，瓦斯。在我們開始提問之前，我只想介紹一下我們今年計劃舉辦的一些投資者活動。首先，我們將於 6 月 2 日在芝加哥的 ASCO 舉辦現場活動，重點介紹 Vas 提到的 Scemblix ASC4FIRST 數據。今年下半年，我們還將舉辦一場有關腎臟管道的虛擬活動。我們將於 11 月 20 日至 21 日在倫敦舉辦一年一度的諾華管理層見面會。

And with that, operator, let's open the line for questions, please.

那麼，接線員，請讓我們開通提問線路。

(Operator Instructions) And your first question comes from the line of Matthew Weston, UBS.

（操作員說明）您的第一個問題來自瑞銀集團 (UBS) Matthew Weston 的電話。

It's going to be on Pluvicto. And so Vas, you set out some of the metrics in terms of improving revenue. I think there's definitely an expectation amongst investors that we might see an inflection as supply comes online and physicians get more comfortable with your ability to supply and add nurses and chairs into their networks. I wanted to understand whether you thought that was a realistic assumption or whether or not investors should get more comfortable with a kind of continuous grind in the growth of Pluvicto over the coming quarters?

它將在 Pluvicto 上播出。 Vas，您制定了一些關於提高收入的指標。我認為投資者肯定有這樣的預期：隨著供應上線，醫生對您提供護士和椅子並將其添加到他們的網絡中的能力更加滿意，我們可能會看到變化。我想了解您是否認為這是一個現實的假設，或者投資者是否應該對 Pluvicto 在未來幾季的持續成長感到更加滿意？

Yes. Thanks, Matthew. So first, on Pluvicto, we have resolved our supply issue, but we are still working through, I think, the remnants of the base of patients that were a bit lower in quarter 4, given that we were still working through things then. And when you think about the growth of Pluvicto medium-to-long term, first, we have this post-taxane indication, where you can see we're already annualizing at a pretty healthy blockbuster, $1 billion-plus sales range.

是的。謝謝，馬修。首先，在 Pluvicto 上，我們已經解決了供應問題，但我認為，我們仍在解決第四季度略低的剩餘患者基礎，因為當時我們仍在解決問題。當你考慮 Pluvicto 的中長期成長時，首先，我們有這個後紫杉烷指標，你可以看到我們已經在一個相當健康的重磅炸彈，銷售範圍超過 10 億美元的年化。

And we expect that to steadily grow, and we guided to that indication to being a multibillion dollar, so a $2 billion-plus indication. So we expect it to steadily grow over the coming quarters in that post-taxane setting. And this will be primarily driven by, as I mentioned, expanding the base of medical oncologists who are able to refer into the existing centers. We don't see the opportunity at this point in terms of expanding the number of centers for this indication.

我們預計這一數字將穩定成長，我們將該指標引導至數十億美元，即超過 20 億美元。因此，我們預計在後紫杉烷環境下，未來幾季它將穩定成長。正如我所提到的，這主要是由於擴大能夠參考現有中心的腫瘤內科醫生的基礎而推動的。目前我們沒有看到擴大該適應症中心數量的機會。

So that will steadily grow over the course of 2024 to get us steadily marching up towards that multibillion-dollar guidance, $2 billion-plus guidance that we've given in the vision indication. Then we expect the PSMAfore pre-taxane indication to be the next catalyst, and we do expect an inflection on that launch which will then -- I should also mention in Pluvicto outside of the U.S. as well, we will get additional momentum as we bring on board Germany, France, other countries in Europe. And then in the coming years, we do expect a substantial inflection from China and Japan. We're building dedicated manufacturing facilities for those countries in order to drive further growth, both in the pre-taxane and the post-taxane indication.

因此，這一數字將在 2024 年穩步增長，使我們穩步邁向我們在願景指示中給出的數十億美元的指導，即超過 20 億美元的指導。然後，我們預計PSMAfore 紫杉烷前指示將成為下一個催化劑，並且我們確實預計該發布將出現變化——我還應該在美國以外的Pluvicto 中提到，我們將獲得額外的動力，因為我們帶來了德國、法國和歐洲其他國家的船上。在未來幾年，我們確實預計中國和日本將發生重大變化。我們正在為這些國家建造專門的生產設施，以推動紫杉烷前和紫杉烷後適應症的進一步成長。

Next catalyst will be the pre-taxane approval, which we hope to have in the first half of next year. Then the hormone-sensitive indication than the oligometastatic. And then we also have 2 programs advancing with actinium PSMA as well to also further bolster the overall portfolio. So I think a steady growth in the VISION indication within catalysts coming from ex-U.S. expansion and the indication expansions for the brand.

下一個催化劑將是紫杉烷前的批准，我們希望在明年上半年獲得批准。那麼激素敏感的指徵比寡轉移多。此外，我們還有 2 個與錒 PSMA 一起推進的項目，以進一步增強整體產品組合。因此，我認為 VISION 指標的穩定成長來自美國以外的催化劑。品牌的擴張和適應症的擴張。

Your next question comes from the line of Steve Scala from TD Cowen.

您的下一個問題來自 TD Cowen 的 Steve Scala。

Vas, you noted in the prepared remarks that the Kisqali review was on track, but how confident is Novartis that FDA will meet the priority review regulatory deadline for Kisqali with a broad label? There seems to be a number of things that could give FDA pause, including the nitrosamine issue as well as liver tox. So what is your level of confidence?

Vas，您在準備好的發言中指出，Kisqali 審查已步入正軌，但諾華公司對 FDA 滿足寬標籤 Kisqali 優先審查監管期限的信心有多大？似乎有很多事情可能會讓 FDA 暫停，包括亞硝胺問題和肝臟毒性。那麼您的信心程度是多少呢？

Yes, Steve, we're very confident on the broad label. I think on the timeline, we currently guide to the current timeline that we have as we implement these manufacturing shifts. We of course, are discussing these manufacturing adjustments and they're minor adjustments, but they do require discussions with FDA. And so once we have a better clarity on -- if at all, if there was any shift in timeline, we would, of course, let the markets know. But we think this will be still a second-half launch for this medicine, and we feel very good about that guidance. And so while we talk here about minor shifts, we're not talking about anything significant. And again, expect the broad label.

是的，史蒂夫，我們對廣泛的標籤非常有信心。我認為在時間表上，我們目前在實施這些製造轉變時遵循當前的時間表。當然，我們正在討論這些生產調整，它們是微小的調整，但它們確實需要與 FDA 進行討論。因此，一旦我們更清楚地了解——如果有的話，如果時間表有任何變化，我們當然會讓市場知道。但我們認為該藥物仍將在下半年推出，我們對這項指導感到非常滿意。因此，當我們在這裡談論微小的轉變時，我們並不是在談論任何重大的事情。再次，期待廣泛的標籤。

We don't have concerns about liver. This is something that's well known with Kisqali, LFTs are currently monitored in the metastatic breast cancer setting. No change in monitoring requirements is what we expect. So overall, we feel good with the ability to launch this medicine in the second half of the year.

我們不擔心肝臟。 Kisqali 眾所周知，目前在轉移性乳癌環境中監測 LFT。我們期望監控要求不會改變。總的來說，我們對今年下半年推出這種藥物的能力感到滿意。

Your next question comes from the line of Graham Parry, Bank of America.

您的下一個問題來自美國銀行格雷厄姆·帕里。

Another one on Kisqali, just -- could you just explain just what the process amendment needed for Kisqali is in early breast cancer? So is that something in the actual reaction? Is it purification? And do you know at the moment whether you do or don't need an inspection by FDA? And if there is one, do you think that would still be completed within the second quarter time frame and therefore, not delay the NATALEE PDUFA timeline.

另一項關於 Kisqali 的問題，您能否解釋一下 Kisqali 治療早期乳癌所需的流程修正是什麼？那麼這是實際反應中的事情嗎？是淨化嗎？現在您知道是否需要 FDA 檢查嗎？如果有的話，您是否認為仍會在第二季度的時間範圍內完成，因此不會延遲 NATALEE PDUFA 的時間表。

Graham. So first on the manufacturing adjustments that we talked about here. Just as a reminder, Kisqali already meets the requirements in metastatic breast cancer. So these are just additional requirements given that early breast cancer is an asymptomatic population. The adjustments we talked about here are primarily how we source material from third parties. We want to go to higher quality sourcing of third-party material, which is something we believe we can implement in a very straightforward way. And then also just some additional adjustments within our supply chain for the management of Kisqali prior to actually leaving our supply chain to go to physicians.

格雷厄姆.首先是我們在這裡討論的製造調整。提醒一下，Kisqali 已經符合轉移性乳癌的要求。因此，鑑於早期乳癌是無症狀人群，這些只是額外的要求。我們在這裡討論的調整主要是我們如何從第三方取得材料。我們希望採購更高品質的第三方材料，我們相信我們可以以非常簡單的方式實現這一目標。然後，在真正離開我們的供應鏈去看醫生之前，我們的供應鏈中還需要對 Kisqali 的管理進行一些額外的調整。

So these are we believe relatively minor changes. Nonetheless, changes we do need to review with the regulators. In terms of inspection, we don't believe there would be any inspection required for this. And so that's what I think overall gives us confidence in the guidance to launch the medicine in the second half.

所以這些是我們認為相對較小的變化。儘管如此，我們確實需要與監管機構一起審查這些變化。在檢查方面，我們認為不需要對此進行任何檢查。因此，我認為這總體上讓我們對下半年推出該藥物的指導充滿信心。

Your next question comes from the line of Emily Field from Barclays.

您的下一個問題來自巴克萊銀行的艾米麗·菲爾德。

I just want to ask a question on Cosentyx. I know you mentioned you're expecting the J-code, but are you currently generating much sales from the IV formulation just in that context, if you could frame the current pricing environment in the U.S. specifically?

我只是想問一個關於Cosentyx的問題。我知道您提到您正在期待 J 代碼，但是如果您能具體說明美國當前的定價環境，您目前是否在這種情況下從 IV 配方中獲得了大量銷售？

Yes. Thanks, Emily. So Cosentyx IV, I'd say better-than-expected uptake than what we had thought prior to the J-code. But when you look at Cosentyx current outperformance in the quarter, it was driven primarily by the strong hidradenitis suppurativa launch as well as that leading to stronger performance as well in psoriasis globally. So the IV launch is still, I think, in the midst of kicking up.

是的。謝謝，艾米麗。因此，我想說 Cosentyx IV 的採用率比我們在 J 程式碼之前的預期要好。但當你看看 Cosentyx 當前季度的優異表現時，你會發現它主要是由於化膿性汗腺炎的強勁上市以及全球牛皮癬領域的強勁表現所推動的。因此，我認為 IV 的發布仍在進行中。

What I would say is we are having a -- we have reached already the vast majority of accounts that we expected to order Cosentyx IV. They're already at least in the process of ordering the medicine ahead of the J-code, trying to use an exceptional code to use the medicine. So in terms of account reach, we're already in a very good position. And we think we'll be able to then drive a strong depth once we actually get the J-code in place. So we feel very good. So this could be another, I think, good driver for Cosentyx growth in the second half post that J-code being rolled out.

我想說的是，我們已經接觸到了我們預計訂購 Cosentyx IV 的絕大多數客戶。他們至少已經在 J 代碼之前訂購藥物，嘗試使用特殊代碼來使用藥物。因此，就客戶覆蓋範圍而言，我們已經處於非常有利的位置。我們認為，一旦 J 程式碼真正到位，我們就能夠推動更深入的發展。所以我們感覺很好。因此，我認為，這可能是 J-code 推出後下半年 Cosentyx 成長的另一個好動力。

Your next question comes from the line of Simon Baker, Redburn Atlantic.

您的下一個問題來自 Redburn Atlantic 的 Simon Baker。

It's a broad question on the commercial performance. Vas, you've highlighted a few specific reasons for strength in the quarter like the Cosentyx HS launch but to what extent is the broad-based performance we've seen in this quarter, a result of the changes to the commercial organization that have been underway over the last couple of years? I wonder to what extent that is responsible if you could give any color on where it's impacting? And how much is there left to come from that initiative?

這是一個關於商業表現的廣泛問題。 Vas，您強調了本季表現強勁的一些具體原因，例如 Cosentyx HS 的推出，但我們在本季度看到的廣泛表現在多大程度上是由於商業組織發生變化而造成的？ ？我想知道這在多大程度上負責，如果你能對它的影響給出任何顏色嗎？該倡議還剩下多少成果？

Yes. Thanks, Simon. We do believe that probably the biggest -- big picture driver for our strong performance over the recent quarters has been the reorganization and focus of the -- focusing of the company. And as a reminder for investors, a few things we did, we elevated the U.S. and we went to a geographic model, U.S., international; we focused down the portfolio to 4 key therapeutic areas; we focus the commercial area on 9 key drugs; we shifted our investments in most places, over 75% of the M&S investments go to the growth drivers; a heavy focus on U.S., China, Japan and Germany. And taken together, that I think is compounding to show the broad-based performance you see across the U.S. and international and particularly in some markets like China, very, very strong performance.

是的。謝謝，西蒙。我們確實相信，最近幾季我們強勁業績的最大推動因素可能是公司的重組和重點。作為對投資者的提醒，我們做了一些事情，我們提升了美國，我們進入了地理模型，美國，國際；我們將產品組合集中到 4 個關鍵治療領域；我們將商業領域聚焦於9個重點藥品；我們在大部分地方都進行了投資轉移，馬莎投資75%以上投向了成長動力；重點關注美國、中國、日本和德國。總而言之，我認為這一點複合了你在美國和國際上看到的廣泛表現，特別是在中國等一些市場，表現非常非常強勁。

So that is, I think, the biggest sustainable driver. In terms of specifics in the quarter, clearly, Cosentyx performed extremely well. Putting aside consensus, if you look at the growth rates of Kisqali and Kesimpta, Leqvio, Scemblix these were all very, very strong, even Pluvicto, if we put aside on -- quarter-on-quarter growth. These were all very strong growth rates. And I think that also, I think, gives us confidence to raise the guidance for the full year.

所以我認為這是最大的永續驅動力。就本季的具體情況而言，顯然 Cosentyx 的表現非常出色。撇開共識不談，如果你看看 Kisqali 和 Kesimpta、Leqvio、Scemblix 的成長率，如果我們拋開季度環比成長的話，這些公司都非常非常強勁，甚至 Pluvicto 也是如此。這些都是非常強勁的成長率。我認為這也讓我們有信心提升全年的指導。

Your next question comes from the line of Emmanuel Papadakis from Deutsche Bank.

您的下一個問題來自德意志銀行的 Emmanuel Papadakis。

Since you flagged it will be forthcoming at ASCO, perhaps just a question on Scemblix ASC4FIRST data details. The primary end point was MMR so we're going to be very interested to see how that fares, obviously, to physician standard or physician's choice, standard care control arm versus the potential comparators in particular, (inaudible) there, can you talk a little bit about what we could expect to see in terms of some of the standard-of-care competitors on that primary endpoint? And indeed, any secondaries you're willing to provide thoughts would be helpful as well.

既然您標記它將在 ASCO 上發布，也許只是關於 Scemblix ASC4FIRST 數據詳細資訊的問題。主要終點是 MMR，因此我們非常有興趣了解其對醫生標準或醫生選擇、標準護理對照組與潛在比較器的影響，尤其是（聽不清楚），您能談談嗎？在該主要終點方面我們可以期望看到什麼？事實上，您願意提供的任何次要想法也會有所幫助。

Yes. Let me outline how the Scemblix study was designed and then hopefully give you some perspective. So this was a first-line study, and this is, of course, our third medicine in the world of chronic myelogenous leukemia, so a long history in the company.

是的。讓我概述一下 Scemblix 研究的設計方式，希望能給您一些看法。所以這是一項一線研究，當然，這是我們在慢性骨髓性白血病領域的第三種藥物，因此公司歷史悠久。

The primary endpoint was Scemblix versus investigator choice TKI with a goal that over 50 -- roughly 50% of patients would be on imatinib or Gleevec. And the primary endpoint was Scemblix versus the overall pool of patients' intention to treat regardless of TKI. So that's first primary endpoint. And the co-primary endpoint was Scemblix versus Gleevec. And we hit both of those primary endpoints with clinically meaningful, highly statistically significant improvements in MMR.

主要終點是 Scemblix 與研究者選擇的 TKI 對比，目標是超過 50%（約 50%）的患者將服用伊馬替尼或格列衛。主要終點是 Scemblix 與整體患者的治療意圖（無論是否使用 TKI）。這是第一個主要終點。共同主要終點是 Scemblix 與 Gleevec 的比較。我們達到了這兩個主要終點，並在 MMR 方面取得了具有臨床意義且具有高度統計顯著性的改善。

Then we had a descriptive secondary endpoint of Scemblix versus the 2 second-gen TKIs. And again, there, we will disclose the full data at ASCO, but we feel very good about the profile of the medicine. And then on safety, which I think is one of the key elements of Scemblix story already in the third-line setting, we saw outstanding safety profile. So I think that's the other thing to look out for at the ASCO presentation is the overall safety profile of Scemblix because clearly, to move into that frontline setting, physicians will want to see both strong efficacy and a clean safety profile.

然後我們獲得了 Scemblix 與 2 個第二代 TKI 的描述性次要終點。再次強調，我們將在 ASCO 中披露完整數據，但我們對該藥物的概況感到非常滿意。然後在安全性方面，我認為這是 Scemblix 故事的關鍵要素之一，已經在三線環境中，我們看到了出色的安全性。因此，我認為 ASCO 演示中需要注意的另一件事是 Scemblix 的整體安全性概況，因為顯然，要進入一線環境，醫生將希望看到強大的功效和乾淨的安全性概況。

Now it's important to note that once we get to the point of filing the medicine shortly and then ultimately launch the medicine, in the U.S., we believe there's a portion of the market where we can drive very rapid uptake. These are patients who are currently on second-gen TKIs or in physician practices that are very open to switching.

現在重要的是要注意，一旦我們很快就達到藥物備案並最終在美國推出該藥物，我們相信我們可以推動非常快速的市場吸收。這些患者目前正在接受第二代 TKI 治療，或正在接受治療的患者非常願意更換治療。

We do know that there is an element of the CML market that's contracted and that tends to use generic imatinib, that will take us longer to -- overall to move through. But I think one of the exciting things about Scemblix is that this has a long LoE and based on targeting a rare disease, it's not part of IRA negotiations. So we have here a medicine that can drive Novartis growth through this decade and well into next decade, both U.S. and around the globe. And we, of course, are one of the global leaders in CML. So I think that positions us well overall.

我們確實知道 CML 市場的一部分已經收縮，並且傾向於使用仿製藥伊馬替尼，這將需要我們更長的時間才能完成。但我認為 Scemblix 令人興奮的事情之一是，它有很長的 LoE，並且基於針對罕見疾病，它不是 IRA 談判的一部分。因此，我們這裡有一種藥物可以推動諾華在本十年乃至下一個十年在美國和全球範圍內的成長。當然，我們是 CML 領域的全球領導者之一。所以我認為這使我們總體上處於有利地位。

Your next question comes from the line of Richard Vosser from JPMorgan.

您的下一個問題來自摩根大通的理查德·沃瑟（Richard Vosser）。

Can I return to Cosentyx? And you mentioned the launch in HS being sort of 3x Humira. How do you see the sizing of the indication of HS now? Is that a $2 billion to $3 billion indication for Cosentyx? And thus, do you see continued potential double-digit growth over the next few years for the product?

我可以返回蘇金單抗嗎？您提到 HS 的推出類似於 3x Humira。您現在如何看待HS指示的尺寸？這是 Cosentyx 的 20 億至 30 億美元適應症嗎？因此，您認為該產品在未來幾年內是否有持續兩位數成長的潛力？

And I suppose one just clarification just to -- any quantification on the HS -- size of the HS contribution at this stage? And I don't think there was any pricing or stocking in the first quarter, but just to clarify that as well.

我想需要澄清一下——對 HS 的任何量化——現階段 HS 貢獻的大小？我認為第一季沒有任何定價或庫存，但這只是為了澄清這一點。

Yes. Thanks, Richard. So just as context, we estimate as best we can from public information that adalimumab had over $1 billion in sales in HS historically. We do think that the market is significantly underserved. There's a large number of patients who are not on biologics in this indication. So it could be a substantial market.

是的。謝謝，理查。因此，正如上下文一樣，我們根據公開資訊盡可能估計阿達木單抗在 HS 領域的銷售額歷史上超過 10 億美元。我們確實認為市場服務嚴重不足。有大量患者未使用此適應症的生物製劑。所以這可能是一個巨大的市場。

I don't think we've given yet guidance on specifically the overall size of the market. But certainly, there's a potential of a multibillion-dollar market here. So we think Cosentyx has the opportunity to drive very significant growth for the brand as we try to reach $7 billion, probably not in a position yet to give specific indication-based guidance on Cosentyx, but we think with the combination of HS, of IV, giant cell arteritis Phase II, which is ongoing, the Polymyalgia Rheumatica indication that we also have as well as the strong performance we have in China that just gives us even more conviction that we can get to that $7 billion peak sales by the end of the decade.

我認為我們還沒有就市場的整體規模給出具體的指導。但可以肯定的是，這裡蘊藏著數十億美元的市場潛力。因此，我們認為 Cosentyx 有機會推動品牌非常顯著的成長，因為我們試圖達到 70 億美元，可能還無法對 Cosentyx 提供基於具體適應症的指導，但我們認為透過 HS 和 IV 的結合，鉅細胞動脈炎第二期，正在進行中，風濕性多肌痛表明我們也有，以及我們在中國的強勁表現，這讓我們更有信心，我們可以在年底前達到70 億美元的峰值銷售額十年。

Your next question comes from the line of Tim Anderson, Wolfe Research.

您的下一個問題來自沃爾夫研究中心的蒂姆·安德森。

I have a couple of questions on Entresto and just timing of generic entry. So in the U.S., can you map out for us what we should be tracking from here in terms of events and news flow that will help inform whether mid-'25 is a good assumption. And as we've conceived well that sometime in '24, you'll have a different point of view.

我有幾個關於 Entresto 和通用進入時間的問題。那麼在美國，您能否為我們規劃我們應該從這裡追蹤的事件和新聞流，這將有助於判斷 25 年中期是否是一個好的假設。正如我們所設想的那樣，在 24 年的某個時候，您將會有不同的觀點。

And then ex-U.S. and the timing of generic entry, you guide for later '26, is there a similar level of uncertainty on that and then if you could wrap-in China as part of that discussion on generic timing as well.

然後是美國以外的地方以及通用進入的時機，您將在 26 年晚些時候進行指導，是否存在類似程度的不確定性，然後您是否也可以將中國納入通用時機討論的一部分。

Yes. Thanks, Tim. So on Entresto right now, we do have an appeal ongoing to the Circuit Court on the combination patent, which we believe will be heard and ruled on in the second half of this year. It's important to note that there have been no Entresto generics approved as of yet, and we have 2 citizen's petitions pending at the FDA on the basis for approval and also the labeling for any potential product with respect to Entresto.

是的。謝謝，蒂姆。因此，目前就 Entresto 而言，我們確實正在向巡迴法院就組合專利提出上訴，我們相信上訴將在今年下半年進行審理和裁決。值得注意的是，到目前為止還沒有 Entresto 仿製藥獲得批准，我們有 2 份公民請願書正在 FDA 等待批准，以及任何與 Entresto 相關的潛在產品的標籤。

So based on that fact that we don't expect any generics to launch this year that we can never exclude, of course, somebody trying to do something at risk. And then separate from that, we have a number of other patents that are currently being litigated towards the end of this year and then towards the -- all through the coming period, which is what overall makes us have the best estimate in the U.S. of mid-2025. And of course, as we get better resolution on that, we can, of course, provide further color.

因此，基於這樣一個事實，我們預計今年不會推出任何仿製藥，當然，我們永遠不能排除有人試圖做一些有風險的事情。除此之外，我們還有許多其他專利目前正在進行訴訟，這些專利將在今年年底以及接下來的整個時期內進行訴訟，這總體上使我們對美國的專利進行了最佳估計2025 年中期。當然，當我們獲得更好的解析度時，我們當然可以提供更多的顏色。

I would also say that Entresto is on the IRA negotiation list so that we would expect in Jan 2026 to our best understanding, at least in the Medicare population that IRA pricing would hold, and we would get a better read on how that looks in September. Outside of the United States, we already include our pediatric exclusivity. So we think our current guide of end of 2026 is reasonable. Of course, we're always looking for ways to adequately defend all of our patents, but we think that's a very reasonable assumption at this point in time.

我還想說，Entresto 已在 IRA 談判名單上，因此我們期望在 2026 年 1 月能夠最好地了解 IRA 定價將保持不變的醫療保險人群，並且我們將在 9 月更好地了解情況。在美國以外的地區，我們已經納入了我們的兒科獨家產品。所以我們認為我們目前對 2026 年底的指導是合理的。當然，我們一直在尋找充分保護我們所有專利的方法，但我們認為目前這是一個非常合理的假設。

In China, at the moment, we currently have, I think, a number of different approaches, but the key there will be the number of generics and when they get approved. And so I think we could reasonably expect potential entry of Chinese generics sometime in the course of 2025. But the question in China was when we will enter the VBP list. And that, of course, is something we're monitoring. And once we have a better understanding of the number of generics and their status legally when we enter the VBP list, we'll be able to provide further clarity.

我認為，目前在中國，我們有多種不同的方法，但關鍵在於仿製藥的數量以及它們何時獲得批准。因此，我認為我們可以合理地預期中國仿製藥可能會在 2025 年的某個時候進入。當然，這是我們正在監控的事情。當我們進入 VBP 清單時，一旦我們更好地了解仿製藥的數量及其合法狀態，我們將能夠提供進一步的清晰度。

And lastly, in Japan, we currently outlook 2031, I believe -- 2031 or 2032. Our team will get back to you exactly. But certainly into the 2030s for Japan at the current point in time. So hopefully, that's helpful, Tim. Thank you for the question.

最後，在日本，我們目前展望 2031 年，我相信是 2031 年或 2032 年。但目前日本肯定會進入 2030 年代。希望這對您有所幫助，蒂姆。感謝你的提問。

Your next question comes from the line of Richard Parkes, BNP Paribas.

您的下一個問題來自法國巴黎銀行的理查德帕克斯。

Just wondered if you could help us with cost phasing. I think guidance is implying a lower margin improvement than the very strong margin improvement you saw in Q1. And I know that was slightly mismodeled last year going into Q4, extrapolating the margin. So can you just help us understand the phasing in terms of costs over this year? That would be very helpful.

只是想知道您是否可以幫助我們進行成本分階段。我認為指引意味著利潤率改善幅度低於您在第一季看到的非常強勁的利潤率改善幅度。我知道去年進入第四季時，推斷利潤率的模型略有錯誤。那麼您能否幫助我們了解今年成本的分階段情況？這將非常有幫助。

Thanks, Richard. I'll hand that to Harry. Harry?

謝謝，理查。我會把它交給哈利。哈利？

Thank you, Richard. So overall, as you have seen, our quarter 1 costs were growing in constant currency, roughly 2%, which was driven by R&D right up -- roughly 6%, whilst SG&A was basically flat. That's a consequence also of the full implementation of transformation for growth, restructuring programs, leaning out, going to 1 organization locally between pharma, onco and leaning out above country and customer-facing functions, our organizational structures and leaning our processes. So we see some continued benefits from that.

謝謝你，理查。因此，總體而言，正如您所看到的，我們第一季的成本以固定匯率計算增長了大約 2%，這是由研發推動的——大約 6%，而 SG&A 基本上持平。這也是全面實施成長轉型、重組計劃、精實化、在製藥、腫瘤領域建立本地組織、超越國家和麵向客戶的職能、我們的組織結構和精益我們的流程的結果。所以我們看到了一些持續的好處。

Of course, we will continue to leverage new technologies, leaner processes to keep driving the multiple launches. But all within our 4 therapeutic areas where we have significant commercial infrastructures and medical infrastructures. So I would expect that SG&A continues to be quite flattish. Maybe here or there a bit more investment, but certainly significantly below sales growth.

當然，我們將繼續利用新技術、更精簡的流程來繼續推動多次發布。但在我們的 4 個治療領域內，我們都擁有重要的商業基礎設施和醫療基礎設施。因此，我預計 SG&A 繼續相當平淡。也許這裡或那裡有更多的投資，但肯定大大低於銷售成長。

And then the level of especially development spend depends also a bit on the M&A, in-licensing agenda. So clearly, we have some placeholder for that in the second half of the year as well. And then we will update you after Q2, of course, how things are going, when we have a clear visibility. But overall, very good focus on cost consciousness. As Vas mentioned, excellent resource allocation to our top 9 brands and pre-launches. And with that, as always, outlook. The key contribution to our margin growth is expected to come from SG&A as we expect very dynamic sales growth this year and on a 5-year basis and very limited SG&A growth.

然後，特別是開發支出的水平也有點取決於併購、授權議程。很明顯，我們在下半年也有一些佔位符。當然，當我們有清晰的了解時，我們將在第二季度之後向您更新情況，當然，事情進展如何。但總的來說，非常注重成本意識。正如 Vas 所提到的，我們為我們的 9 大品牌和預發布產品進行了出色的資源分配。並一如既往地展望未來。我們的利潤成長的主要貢獻預計將來自銷售及管理費用，因為我們預計今年和五年內的銷售成長將非常活躍，而銷售及管理費用成長非常有限。

Your next question comes from the line of Mark Purcell from Morgan Stanley.

您的下一個問題來自摩根士丹利的馬克·珀塞爾。

It's on Scemblix. I wonder, Vas, if you could help us understand the level of uptake you anticipate in the first-line setting. The slide shows 40% NBRx share in the third-line setting, and you talked about the sort of potential ease of identifying specific patients who might most likely benefit from Scemblix versus the current standard TKIs.

它在 Scemblix 上。我想知道，Vas，您是否可以幫助我們了解您在一線環境中預期的吸收程度。這張投影片顯示了 NBRx 在三線環境中的份額為 40%，您談到了識別最有可能從 Scemblix 與當前標準 TKI 中受益的特定患者的潛在便利性。

And I also wondered on Scemblix. Have you seen any early impacts of the Part D redesign when it comes to treatment initiations and volumes? Any sort of comment there for Scemblix and across your business would be great.

我也對 Scemblix 感到好奇。您是否看到 D 部分重新設計對治療啟動和治療量的任何早期影響？對於 Scemblix 和您的企業的任何評論都會很棒。

Yes. Thanks, Mark. I think on Scemblix, we would expect, I would say, a modest early uptake because we would have to work through -- CML is one of the few cancer areas that's currently contracted. And so we would need to work through the access in the first couple of quarters from launch. But then after that, we believe that given the overall data set that we'll share at ASCO, that it should be able to drive very strong uptake.

是的。謝謝，馬克。我認為在 Scemblix 上，我們預計會得到適度的早期採用，因為我們必須克服 CML 是目前感染的少數癌症領域之一。因此，我們需要在發布後的前幾個季度內解決存取問題。但在那之後，我們相信，考慮到我們將在 ASCO 上分享的整體數據集，它應該能夠推動非常強勁的採用。

And of course, you all know well that the second-gen TKIs were on the order of $2 billion medicines. Gleevec was a $4 billion-plus global medicine. And so certainly, our goal is to make this over time, the leading CML treatment in the world. we wouldn't face any competition, at least branded competition and given that we will have demonstrated MMR superiority over the pooled group of Gleevec and the second-gen TKIs. It should put us in a very good position over time to make this into a significant medicine.

當然，大家都知道，第二代 TKI 的藥品價值約為 20 億美元。格列衛是一種價值超過 40 億美元的全球藥品。當然，我們的目標是隨著時間的推移使其成為世界領先的 CML 治療方法。我們不會面臨任何競爭，至少不會面臨品牌競爭，並考慮到我們將展示相對於格列衛和第二代 TKI 聯合組的 MMR 優勢。隨著時間的推移，它應該使我們處於非常有利的位置，使其成為重要的藥物。

I think on Part D redesign, it's really early days for us to have a strong sense of the impact. And so we're monitoring this very closely, also reading all of your reports on how you're monitoring it to really understand what is the impact of out-of-pocket caps and some of the other shifts that are happening in the system on patients taking up their medicines.

我認為在 D 部分的重新設計中，我們對影響的強烈感知還為時過早。因此，我們正在非常密切地監控這一點，並閱讀你們關於如何監控它的所有報告，以真正了解自付費用上限以及系統中正在發生的一些其他變化的影響。

I think certainly, as we move down from a $3,500 cap to a $2,000 cap, I would expect, in general, to see more patients' ability to fulfill their medicines to improve as the cost becomes lower at the pharmacy counter. But we need to see that, I think, in the data before we can really provide you more color.

我當然認為，當我們將上限從 3,500 美元下調至 2,000 美元上限時，我預計，隨著藥房櫃檯成本的降低，更多患者購買藥品的能力會得到改善。但我認為，我們需要在數據中看到這一點，然後才能真正為您提供更多顏色。

Your next question comes from the line of Peter Welford from Jefferies.

您的下一個問題來自 Jefferies 的 Peter Welford。

It's on the planned proposed MorphoSys transaction. I wonder if you can just outline when you did that, how much of the acquisition price that you're considering was based on getting broad, both geographical and same to the market approval for pelabresib.

這是計劃中的 MorphoSys 交易。我想知道您是否可以概述一下您何時這樣做，您正在考慮的收購價格中有多少是基於廣泛的地理範圍和與 pelabresib 的市場批准相同的情況。

And versus, on the other hand, how much of the transaction is described to what you're thinking with regards to the EZH2 and also the ianalumab royalties that you would potentially owe and how we should think about, I guess, that deal, the potential -- fitting that into the -- for Novartis cost structure, business as it is today.

另一方面，有多少交易描述了您對 EZH2 的想法以及您可能欠下的 ianalumab 特許權使用費，以及我們應該如何考慮該交易，我想，潛力 - 將其納入諾華成本結構和當今的業務。

Yes. Thanks, Peter. Probably, I can't say more than what we've already said, given that we have an ongoing share tender offer out in the market. So what we previously outlined is we believe there is an opportunity globally for pelabresib in both Europe and in the United States, and that's an exciting opportunity given our Jakavi business and the opportunity that we have to leverage our long history in myelofibrosis, and position in myelofibrosis outside the United States and our strong hematology footprint inside the United States.

是的。謝謝，彼得。考慮到我們在市場上正在進行的股票要約收購，我可能不能說的比我們已經說過的更多了。因此，我們之前概述的是，我們相信pelabresib 在歐洲和美國在全球範圍內都有機會，考慮到我們的Jakavi 業務，以及我們必須利用我們在骨髓纖維化方面的悠久歷史和在骨髓纖維化領域的地位，這是一個令人興奮的機會。

So we would see pelabresib as fitting nicely within that global infrastructure that we have. And yes, we would also benefit from the historical royalties, particularly on ianalumab, where we see the opportunity of a significant medicine, both in immunology and in cancer. And so I think that's a pretty exciting opportunity for us to get those royalties back and then hopefully drive very significant medicine with -- a significant medicine in a royalty-free way.

因此，我們認為 pelabresib 非常適合我們擁有的全球基礎設施。是的，我們還將受益於歷史特許權使用費，特別是ianalumab，我們看到了一種重要藥物的機會，無論是在免疫學還是在癌症方面。因此，我認為這對我們來說是一個非常令人興奮的機會，可以收回這些版稅，然後希望以免版稅的方式推動非常重要的藥物的發展。

And then lastly, the company does have an EZH1/2 inhibitor in prostate cancer that we think could also be very interesting for us going forward. So those are the 3 components of why we saw value in the deal.

最後，該公司確實有一種治療前列腺癌的 EZH1/2 抑制劑，我們認為這對我們的未來也非常有趣。這些就是我們看到這筆交易價值的三個組成部分。

Your next question comes from the line of Andrew Baum from Citi.

您的下一個問題來自花旗銀行的安德魯·鮑姆 (Andrew Baum)。

Apologies. Just going back to the ASC4FIRST trial with Scemblix. Could you just expand your previous comments, Vas, on the dynamics of the CNL market, particularly the current market shares in first line, generically versus others, the Medicare versus non-Medicare segmentation, just to help us think about the barriers to entry in a different segment in terms of authorization, step edits.

道歉。回到 Scemblix 的 ASC4FIRST 試驗。 Vas，您能否擴展您先前對 CNL 市場動態的評論，特別是當前一線市場份額、一般與其他市場份額、醫療保險與非醫療保​​險細分，只是為了幫助我們思考進入市場的壁壘授權、步驟編輯方面的不同部分。

Yes. So Andrew, a couple of things. I think, one, we see this is a market that on the order of 40% -- 35% to 40% imatinib so Gleevec generics and 60% TKIs. And then in terms of commercial and Medicare, we can come back to you with the exact data. But my recollection is it's largely evenly split between Medicare and private commercial plans.

是的。安德魯，有幾件事。我認為，第一，我們看到這個市場大約有 40% - 35% 到 40% 的伊馬替尼、格列衛仿製藥和 60% 的 TKI。然後在商業和醫療保險方面，我們可以向您提供準確的數據。但我的記憶是，醫療保險和私人商業計劃基本上各佔一半。

So the way we look at the overall market opportunity in that 60% or so of patients who are on second-gen TKIs, this is an opportunity as this class goes generic to certainly -- and for commercial plans as well, given that we won't have to compete against a rebate from those players, we would certainly have the opportunity to educate physicians on the great profile that we have here particularly around the safety profile, also the efficacy profile and then hopefully drive switches.

因此，從我們看待 60% 左右服用第二代 TKI 的患者的整體市場機會的角度來看，這是一個機會，因為此類藥物肯定會通用，對於商業計劃也是如此，因為我們贏了不必與這些參與者的回扣競爭，我們當然有機會向醫生介紹我們在這裡擁有的良好概況，特別是在安全概況和功效概況方面，然後希望推動開關。

And we see that's the early opportunity for the medicine in that second-gen TKI, particularly second-gen TKI commercial and then eventually the Medicare. We find that patients who are currently on imatinib tend to be in community oncology and tend to be with physicians who have a long history of using imatinib and therefore, might be more resistant to change. And that will take us longer to eventually, I think -- we think, move though. We do think we have good strategies to get there. That segment of the market will be a longer lift for us to eventually move through. So that's in the ex-U.S.

我們看到這是第二代 TKI 藥物的早期機會，特別是第二代 TKI 商業，然後最終是醫療保險。我們發現目前正在使用伊馬替尼的患者往往在社區腫瘤科工作，並且往往與有長期使用伊馬替尼歷史的醫生一起工作，因此可能更抵制改變。不過，我認為，我們認為，這將需要更長的時間才能最終採取行動。我們確實認為我們有很好的策略來實現這一目標。對於我們最終來說，這部分市場將是一個更長的提升。這是在美國以外的地方。

In the U.S. setting, I think ex-U.S. will really vary by geography. Certainly, in Europe, it will be critical for us to demonstrate differentiation with imatinib from a payer standpoint to justify what we think is a fair price for the medicine.

在美國環境中，我認為除美國外確實會因地理位置而異。當然，在歐洲，從付款人的角度證明伊馬替尼的差異化以證明我們認為該藥物的公平價格是合理的，這對我們來說至關重要。

We would expect in Japan, in China, the opportunity for strong uptake. These are markets where we do think we can get reimbursed. And certainly in Japan, there's a very well-educated CML physician community. So that's, I think, a relatively large opportunity as well.

我們預計在日本和中國將有機會大力採用。我們確實認為這些市場是可以得到補償的。當然，在日本，有一個受過良好教育的 CML 醫生群體。所以我認為這也是一個相對較大的機會。

So that's kind of the high-level dynamics. But I think at the ASCO presentation in June, we can provide more insights into the overall market structure and how we're seeing the opportunity to launch the medicine.

這就是高層動態。但我認為在 6 月的 ASCO 演講中，我們可以提供有關整體市場結構以及我們如何看待推出該藥物的機會的更多見解。

Your next question comes from the line of Seamus Fernandez from Guggenheim Securities.

您的下一個問題來自古根漢證券公司的 Seamus Fernandez。

So really, I just wanted to focus in on IgAN and some of the activity that we're seeing from a competitive perspective there and acquisitions in the space. So I just wanted to get your thoughts on the acquisitions that you've made in IgAN and the opportunity that you see in that space, whether it be for iptacopan or for the acquisitions that you've made? I know you specified a lot of opportunity there. But interested to sort of see if you view this as a validation of the IgAN market opportunity and how you're thinking about the competitive landscape going forward?

所以實際上，我只是想專注於 IgAN 以及我們從競爭角度看到的一些活動以及該領域的收購。所以我只是想了解您對 IgAN 收購的想法以及您在該領域看到的機會，無論是 iptacopan 還是您進行的收購？我知道你在那裡指定了很多機會。但有興趣了解您是否認為這是 IgAN 市場機會的驗證以及您如何看待未來的競爭格局？

Yes. Thanks, Seamus. So in general, I mean, IgAN is, we believe, a significant market opportunity. These patients don't have -- historically have not had great medicines. They do progress at a relatively high rate in the 10-year period towards needing transplantation or going on to dialysis. And we're talking about a segment here that's over 130,000 patients in the U.S. alone. So we think it is a sizable opportunity.

是的。謝謝，西莫。所以總的來說，我的意思是，我們相信 IgAN 是一個重要的市場機會。這些患者在歷史上沒有得到很好的藥物。在 10 年期間，他們確實以相對較高的速度進展到需要移植或繼續透析。我們在這裡討論的是僅在美國就有超過 13 萬名患者的細分市場。所以我們認為這是一個相當大的機會。

When we think about the treatment paradigm, you -- of course, you start out -- you want to -- historically, this has been a steroid-driven treatment paradigm, but we think this will shift to wanting to somehow manage the hemodynamic component of the medicine -- of these patients where we have atrasentan.

當我們考慮治療模式時，你——當然，你開始——你想要——從歷史上看，這是一種類固醇驅動的治療模式，但我們認為這將轉變為想要以某種方式管理血流動力學部分藥物－我們使用阿曲生坦的這些病人。

You want to manage then the inflammatory component for these patients along 2 dimensions, complement inhibition and APRIL inhibition as well. Now we're in a position where we will have atrasentan for hemodynamic inhibition. We'll have iptacopan for complement inhibition, and we'll have Zigakibart also acquired in our Chinook acquisition for the anti-APRIL component. We acknowledge there will be competitors, particularly on the anti-APRIL side of things where we're going to have a few other competitors enter.

然後，您需要從兩個維度管理這些患者的發炎成分，即補體抑制和 APRIL 抑制。現在我們將使用阿曲生坦來抑制血流動力學。我們將使用 iptacopan 來抑制補體，並且我們還將在 Chinook 收購中獲得 Zigakibart，用於抗 APRIL 成分。我們承認會有競爭對手，特別是在反四月方面，我們將有一些其他競爭對手進入。

We believe we'll be the only company positioned with really the full range of hemodynamic, complement, ANTI-April. I should note as well, of course, upstream the SGLT2 inhibitors, which are also going generic will also be part of that early-treatment paradigm. But post SGLT2 inhibitors and perhaps generic hypertensives, you're going to want to move down this paradigm of really more potent hemodynamic control and then also trying to get to the inflammatory component.

我們相信，我們將成為唯一一家真正擁有全方位血流動力學、補體、ANTI-April 的公司。當然，我還應該指出，SGLT2 抑制劑的上游也將成為早期治療範例的一部分，這些抑制劑也將成為通用藥物。但在 SGLT2 抑制劑和普通高血壓治療之後，您將需要放棄這種真正更有效的血流動力學控制模式，然後嘗試解決發炎問題。

And we think having 3 medicines will allow us to be well positioned with patients, physicians, contracting the various elements of the U.S. supply chain and also globally. So that's how we're approaching it. I do think the recent acquisitions do point to that anti-APRIL and this whole area is exciting, right? And we have an asset there, others now are also coming but certainly something we're looking at very carefully to also see can you expand APRIL inhibition with or without BAFF inhibition for other indications as well.

我們認為，擁有 3 種藥物將使我們能夠與患者、醫生建立良好的關係，並與美國乃至全球供應鏈的各個要素簽訂合約。這就是我們的處理方式。我確實認為最近的收購確實表明了反四月的趨勢，整個領域都令人興奮，對吧？我們在那裡有一個資產，其他人現在也來了，但我們肯定正在非常仔細地研究，看看你是否可以在有或沒有 BAFF 抑制的情況下擴大 APRIL 抑制用於其他適應症。

Your next question comes from the line of Eric Le Berrigaud from Stifel.

您的下一個問題來自 Stifel 的 Eric Le Berrigaud。

We saw the split in sales by geography on Leqvio being significantly different from the past and now ex-U.S. being more significant than U.S. Could you maybe elaborate a little bit on the kind of agreements you reached in ex-U.S. territories, maybe the main 3 markets in Europe and China, how the drug is delivered? How are you billing for the drug in those geographies?

我們發現 Leqvio 上按地理位置劃分的銷售分佈與過去和現在的美國以外地區有顯著差異。比美國更重要 您能否詳細說明您在美國以外地區達成的協議類型地區，也許是歐洲和中國這三個主要市場，藥物是如何交付的？您在這些地區的藥物費用如何？

Yes. Thanks, Eric. We're pleased to see Leqvio now getting to a steady march upward in terms of its overall sales growth. Outside of the United States, there have been a few key dynamics. So first is China self-pay, where I mentioned over 250 patients a day, steady growth as well in terms of the number of patients that were being able to get on treatment in China. And that's ahead of where we hope to get listed -- full listing on the NRDL in the first part of next year. And given the strength of our cardiovascular operations in China with Entresto, we believe we can drive pretty significant uptake of Leqvio over time in China.

是的。謝謝，埃里克。我們很高興看到 Leqvio 現在的整體銷售額成長穩定上升。在美國以外，也出現了一些關鍵動態。首先是中國的自費，我提到每天超過250名患者，能夠在中國接受治療的患者數量也穩定成長。這比我們希望在明年上半年在國家健保目錄全面上市的目標還要早。考慮到我們在中國的 Entresto 心血管業務的實力，我們相信隨著時間的推移，我們可以推動 Leqvio 在中國的大量使用。

We also have reimbursement in Japan, and we're in the very early days of launching in Japan. So Japan was not a significant contributor in Q1, but we expect consistently now in the coming quarters, Japan to be a more significant contribution.

我們在日本也有報銷服務，而且我們正處於在日本推出的早期階段。因此，日本在第一季並不是一個重要的貢獻者，但我們一致地預計，在未來幾個季度，日本將做出更重要的貢獻。

In Europe, we've had very steady uptake in the commercial market in Germany as well as improving performance in Italy and the U.K. And so I mean, the U.K. has been a disappointment relative to where we hoped it would be, but nonetheless, it's steadily moving up as well. And then interestingly, while it's a smaller contributor, given the number of countries around the globe, we have reimbursement, we do have public health agreements in places like the Gulf Coast countries as well as other markets in our international business that's also contributing.

在歐洲，我們在德國商業市場的佔有率非常穩定，在義大利和英國的表現也有所改善。也穩定上升。有趣的是，雖然它的貢獻較小，但考慮到全球國家的數量，我們有報銷，我們在墨西哥灣沿岸國家等地以及我們國際業務中的其他市場也確實有公共衛生協議。

So step by step, all of this comes together to drive the performance that you saw in quarter 1. And we'll see. We hope we can continue that now in the coming quarters and steadily get Leqvio up to that multibillion-dollar outlook that we've given.

因此，所有這些一步一步地共同推動您在第一季看到的業績。我們希望我們能夠在接下來的幾個季度繼續這樣做，並穩步讓 Leqvio 達到我們給出的數十億美元的前景。

Your next question comes from the line of Steve Scala from TD Cowen.

您的下一個問題來自 TD Cowen 的 Steve Scala。

On Entresto, were there any onetime factors driving Q1 sales such as rebates and/or inventory? If not, then what in your opinion led to it not tracking prescriptions in the quarter?

在 Entresto 上，是否有任何一次性因素推動第一季的銷售，例如折扣和/或庫存？如果不是，那麼您認為是什麼導致它沒有追蹤本季的處方？

Yes, Steve, we're not aware of any one-timers on Entresto. We saw strong TRx growth. We saw outstanding growth in China. And I think that was a big driver of the performance you saw in the quarter, also steady uptake in Japan. But no one-timers that we're aware of. Looking at Harry, yes. So no one-timers that we see. This was just underlying performance, and I think driven both in the U.S. but also China and Japan.

是的，史蒂夫，我們不知道有任何一次性使用 Entresto 的人。我們看到了 TRx 的強勁成長。我們在中國看到了出色的成長。我認為這是本季業績的重要推手，也是日本市場穩定成長的推手。但據我們所知，沒有一次性的。看著哈利，是的。所以我們沒有看到一次性的人。這只是基本表現，我認為這不僅是美國的推動，也是中國和日本的推動。

Your next question comes from the line of Graham Parry, Bank of America.

您的下一個問題來自美國銀行格雷厄姆·帕里。

Just wondering in terms of the NATALEE [charges] that we were talking about timing earlier, just what's assumed in your guidance for adjuvant breast cancer for Kisqali for this year? So there's any significant contribution in there, or is that de minimis at this point?

只是想知道就 NATALEE [指控] 而言，我們之前討論過時間安排，您今年對 Kisqali 的輔助乳癌治療指南中的假設是什麼？那麼其中有什麼重大貢獻嗎？

And then just I'll flip in the second one, just at the ASCO event, on Scemblix. So I was wondering if you're going to be in a position to give some sort of updated peak sales guidance for that asset? There's obviously a lot of questions on the call about market [appetite] that's -- what everyone's fishing for.

然後我會在 Scemblix 的 ASCO 活動上翻出第二個。所以我想知道您是否能夠為該資產提供某種更新的高峰銷售指導？顯然，電話會議上有很多關於市場[胃口]的問題，這就是每個人都在尋找的東西。

Yes. Thanks, Graham. On NATALEE, not a material contribution or really any contribution in this year. So I don't think that's something that needs to be factored in, in terms of our guidance. On Scemblix, we'll take it under advisement. I can't commit one way or another, but we'll certainly take the feedback on trying to guide.

是的。謝謝，格雷厄姆。在 NATALEE 上，今年沒有實質貢獻或實際上有任何貢獻。因此，我認為就我們的指導而言，這不是需要考慮的因素。對於 Scemblix，我們會給予建議。我不能以一種或另一種方式做出承諾，但我們肯定會接受嘗試指導的回饋。

It's always tough, of course, before we've even got an approval or launched a medicine to really know the outlook. But I think we've got reasonable benchmarks in the CML market with Gleevec and the second-gen TKIs. And as I outlined, we really believe, but we'll see as we present the data that this can be really the best-in-class medicine to treat CML that's been launched in this industry. So we hope we can live up to that profile.

當然，在我們獲得批准或推出一種藥物來真正了解前景之前，這總是很困難的。但我認為我們在 CML 市場上已經透過格列衛和第二代 TKI 獲得了合理的基準。正如我所概述的，我們確實相信，但當我們提供數據時，我們會發現這確實是該行業推出的治療 CML 的最佳藥物。因此，我們希望我們能夠達到這一目標。

And your final question today comes from the line of Emily Field, Barclays.

今天你的最後一個問題來自巴克萊銀行艾米麗·菲爾德。

Question on ianalumab, given that this morning, we did see Phase III success in ITP from a competitor BTK inhibitor. So I was just wondering given that you also have a BTK inhibitor of your own, why you're pursuing ITP with the BAFF inhibition and you think that, that's the right mechanism of action? And while you're also prioritizing second line or first line, I believe that's what it says, the lead indication in the slides.

關於ianalumab 的問題，鑑於今天早上，我們確實看到競爭對手 BTK 抑制劑在 ITP 中取得了 III 期成功。所以我只是想知道，既然您也有自己的 BTK 抑制劑，為什麼您要透過 BAFF 抑制來追求 ITP，並且您認為這是正確的作用機制？雖然您還優先考慮第二行或第一行，但我相信這就是它所說的，幻燈片中的主要指示。

Yes. So first, on BTK inhibition, we really tried to focus our BTK inhibitor outside of the oncology indications. I mean we look at the indication range we're pursuing, it's immunology, the full range, HS, food allergy, CSU. We have also ideas to pursue remibrutinib in other immunology indications and multiple sclerosis.

是的。因此，首先，在 BTK 抑制方面，我們確實嘗試將 BTK 抑制劑的重點放在腫瘤學適應症之外。我的意思是，我們看看我們正在追求的適應症範圍，它是免疫學、全範圍、HS、食物過敏、CSU。我們也有想法在其他免疫學適應症和多發性硬化症中尋求瑞米魯替尼。

So we've tried to steer clear of the oncology setting overall and really focus ianalumab in both oncology but also in more hard-to-treat immunology indications. Based on our best guidance from FDA and the agreements on the Phase III study, we think this was a stepwise approach in ITP, especially for a subcu medicine like ianalumab. And then, yes, we'll see if we can move into the frontline setting.

因此，我們試圖整體上避開腫瘤學背景，真正將ianalumab 專注於腫瘤學和更難治療的免疫學適應症。根據 FDA 的最佳指導和 III 期研究協議，我們認為這是 ITP 的逐步方法，特別是像 ianalumab 這樣的 subcu 藥物。然後，是的，我們將看看是否可以進入前線環境。

So I think that's probably the best guidance I can give. I'm trying to recall if we looked at remibrutinib in ITP, but we'd have to get back to you, Emily, I just can't recall if we looked at it in our Phase IIa programs. So we can come back to you if we have studied our BTK inhibitor in those indications.

所以我認為這可能是我能提供的最好指導。我試著回憶起我們是否在 ITP 中研究過瑞​​米魯替尼，但我們必須回覆您，艾米麗，我只是不記得我們是否在 IIa 期專案中研究過它。因此，如果我們研究了我們的 BTK 抑制劑在這些適應症中的情況，我們可以回覆您。

So thanks very much. I think that was the last question. So I really appreciate everybody's time today. We look forward to keeping you updated, and we will see you all at our event at ASCO. So thank you and have a great quarter season and wish you a great spring.

非常感謝。我認為這是最後一個問題。所以我非常感謝大家今天抽出時間。我們期待為您提供最新消息，我們將在 ASCO 的活動中與您見面。謝謝您，祝您有個愉快的季度，並祝您度過一個愉快的春天。

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

謝謝。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。