Novartis AG (NVS) 2021 Q1 法說會逐字稿

Good morning and good afternoon, and welcome to the Novartis Q1 2021 Results Release Conference Call and Live Audio Webcast. (Operator Instructions). The conference is being recorded. (Operator Instructions)

早上好，下午好，歡迎來到諾華 2021 年第一季度業績電話會議和現場音頻網絡直播。 （操作員說明）。會議正在錄製中。 （操作員說明）

With that, I would like to hand over to Mr. Samir Shah, Global Head of Investor Relations. Please go ahead, sir.

至此，我想向投資者關係全球主管 Samir Shah 先生匯報。請繼續，先生。

Thank you very much, and good morning and good afternoon, everybody. Thank you for taking the time to join us on the Q1 results conference call. We appreciate that you are taking this time.

非常感謝大家，大家早上好，下午好。感謝您抽出寶貴時間參加第一季度業績電話會議。感謝您抽出這段時間。

Before we start, I just want to go through the safe harbor statement. 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.

在我們開始之前，我只想通過安全港聲明。今天提供的信息包含涉及已知和未知風險、不確定性和其他因素的前瞻性陳述。這些可能導致實際結果與此類陳述所表達或暗示的任何未來結果、業績或成就存在重大差異。有關其中一些因素的描述，請參閱公司的 20-F 表格及其最近的 6-K 表格季度業績，這些業績分別提交給美國證券交易委員會並提供給美國證券交易委員會。

And with that, I'll now hand across to Vas.

有了這個，我現在將交給 Vas。

Thank you, Samir, and thanks, again, for everyone for joining today's conference call. With me today I have Harry Kirsch, our Chief Financial Officer; Marie-France Tschudin, our President, Novartis Pharmaceuticals; Susanne Schaffert, our President, Novartis Oncology; John Tsai, our Head of Global Drug Development and Chief Medical Officer; Richard Saynor, our Head of Sandoz; Tom Kendris, who is our Chief Legal Officer ad interim; and Samir, who you've just heard from.

謝謝你，薩米爾，再次感謝大家參加今天的電話會議。今天和我在一起的是我們的首席財務官 Harry Kirsch； Marie-France Tschudin，我們的諾華製藥總裁； Susanne Schaffert，諾華腫瘤學總裁；我們的全球藥物開發主管兼首席醫療官 John Tsai；山德士負責人 Richard Saynor； Tom Kendris，我們的臨時首席法務官；還有薩米爾，你剛剛聽到他的消息。

So moving to the next slide. What I'd like to do is give you an overview of our performance and then dive a little bit deeper into the 4 key areas as part of the overview section before handing it over to our business leaders.

所以轉到下一張幻燈片。我想做的是讓您對我們的表現進行概述，然後在將其移交給我們的業務領導之前，作為概述部分的一部分，更深入地研究 4 個關鍵領域。

First and foremost, we feel confident in the growth outlook of the company, particularly given the momentum we're seeing in Innovative Medicines and the expected stabilization we foresee in the Sandoz business. From a productivity standpoint, when you control for our forward purchasing, we continued our expansion of our core margin, and I'll say more about that in a moment.

首先，我們對公司的增長前景充滿信心，特別是考慮到我們在創新藥物方面看到的勢頭以及我們對 Sandoz 業務的預期穩定。從生產力的角度來看，當您控制我們的遠期採購時，我們會繼續擴大我們的核心利潤，我稍後會詳細說明。

We had multiple important milestones from an innovation standpoint. And I'll go into a little more depth as to some of the upcoming milestones and some of the updates we have in our Phase II and Phase III pipeline, which we view as one of the leading pipelines in the industry. And lastly, in ESG, we continued to our march to being a sector leader within the pharmaceutical and biopharmaceutical sector as well as being a leader across sectors, ranked #2 in the Access to Medicines Index and #1 in Sustainalytics, and I'll talk a little bit more about that in a moment.

從創新的角度來看，我們有多個重要的里程碑。我將更深入地介紹一些即將到來的里程碑以及我們在第二階段和第三階段管道中的一些更新，我們認為這是業內領先的管道之一。最後，在 ESG 方面，我們繼續努力成為製藥和生物製藥行業的行業領導者以及跨行業的領導者，在藥品獲取指數中排名第二，在 Sustainalytics 中排名第一，我將稍後再談一談。

So going to the next slide, starting with the growth outlook. Our key growth drivers really demonstrated that they're returning to momentum over Q1. We had strong performance in brands such as Entresto, Zolgensma and Cosentyx on the Pharmaceutical side as well as a very good performance from brands like Lutathera, Kymriah and solid performance from Kisqali in the Oncology side. In addition, Kesimpta is off to a very strong start, and Marie-France will talk more about the Kesimpta launch.

所以轉到下一張幻燈片，從增長前景開始。我們的主要增長動力確實表明它們在第一季度恢復了勢頭。我們在製藥方面的 Entresto、Zolgensma 和 Cosentyx 等品牌表現強勁，在 Lutathera、Kymriah 等品牌表現非常出色，在腫瘤學方面表現穩健。此外，Kesimpta 的開局非常強勁，Marie-France 將更多地談論 Kesimpta 的推出。

Now when you take it together, our key growth drivers and launches now are growing 20% and amounting to 48% of our total sales. And we expect this number to continue to climb over the coming years, enabling us to deliver the midterm growth we outlined in the Meet Novartis Management presentation we had last November. As a proof point, when you exclude forward purchasing, our Innovative Medicines business grew 3% in the quarter in constant currencies.

現在，當你把它放在一起時，我們的主要增長動力和發布現在正在增長 20%，占我們總銷售額的 48%。我們預計這一數字將在未來幾年繼續攀升，使我們能夠實現我們在去年 11 月舉行的與諾華管理層見面會上概述的中期增長。作為一個證據，當您排除遠期採購時，我們的創新藥物業務在本季度以固定匯率計算增長了 3%。

Now moving to the next slide. We're also confident that we can continue to deliver the core margin expansion that we've committed to. In the near term, that would be in the mid- to high-30s. In the near term -- excuse me, and in the midterm, it would be in the high 30s. And when you look at our Q1 underlying performance when, again, you take into account forward purchasing that we saw last year, you had core operating growth of plus 6% and core margin growth of 1 point, bringing us to 36.3%, well on our way to getting to that high 30s goal.

現在轉到下一張幻燈片。我們也有信心，我們可以繼續實現我們承諾的核心利潤率擴張。在短期內，這將是在 30 多歲的中高點。在短期內 - 對不起，在中期，它將在 30 多歲。當您再次查看我們第一季度的基本業績時，再次考慮到我們去年看到的遠期採購，您的核心運營增長率為 6%，核心利潤率增長 1 個百分點，使我們達到 36.3%，很好我們實現 30 多歲目標的方式。

The drivers of that expansion were sales momentum on our key products as well as the continued productivity program in Novartis Technical Operations where our goal is to deliver $2 billion in savings in the next few years. And we continue to evolve our ways of working, delivering savings from our newly created Customer & Technology Solutions organization, which integrates data and digital as well as Novartis Business Services to even accelerate the overall way of working inside of Novartis.

這種擴張的驅動力是我們關鍵產品的銷售勢頭以及諾華技術運營部門的持續生產力計劃，我們的目標是在未來幾年內節省 20 億美元。我們繼續改進我們的工作方式，從我們新創建的客戶和技術解決方案組織中節省開支，該組織整合了數據和數字以及諾華商業服務，甚至加速了諾華內部的整體工作方式。

Now moving to Slide 8. Sandoz did have a difficult quarter, which was impacted by price erosion and forward purchasing and a historically low cough and cold season. The first thing to note is we were cycling an exceptionally strong prior year quarter. And you can see some of the figures here. But for example, the total sales of Sandoz was up 11% Q1 2020 and, of course, this quarter were down 13%.

現在轉到幻燈片 8。山德士確實有一個艱難的季度，受到價格侵蝕和提前購買以及歷史上低咳嗽和感冒季節的影響。首先要注意的是，我們在上一季度的表現異常強勁。你可以在這裡看到一些數字。但例如，山德士的總銷售額在 2020 年第一季度增長了 11%，當然，本季度下降了 13%。

Now some of the underlying factors that we see impacting this, many of them are sector-wide, so price erosion of 10%, which we saw across Europe and U.S. in our key markets. I mentioned the forward purchasing as well as weak demand in cough and cold retail as well as some of the impacts of the retention of the Aurobindo business in oral solids in the U.S.

現在我們看到影響這一點的一些潛在因素，其中許多是整個行業的，因此價格下跌了 10%，我們在歐洲和美國的主要市場看到了這種情況。我提到了遠期採購以及咳嗽和感冒零售的疲軟需求，以及保留 Aurobindo 業務在美國口服固體中的一些影響。

On a positive note, our biopharma business continues to grow and continues to be a leader in many regions around the world. We expect business -- the business to stabilize in the second half as the pandemic eases. We expect our biosimilars to outperform in the competitive European market. We expect to see our retail European business rebound. And we also have an increasing number of launches, both across biosimilars in geographies outside of the U.S. and Europe as well as in small molecules in the second half. So that will be a key area of focus for us as we continue to get Sandoz back to growth.

積極的一面是，我們的生物製藥業務繼續增長，並繼續成為全球許多地區的領導者。我們預計業務——隨著大流行的緩解，業務將在下半年企穩。我們預計我們的生物仿製藥將在競爭激烈的歐洲市場表現出色。我們預計我們的歐洲零售業務將出現反彈。而且我們也有越來越多的產品發布，包括美國和歐洲以外地區的生物仿製藥以及下半年的小分子藥物。因此，隨著我們繼續讓山德士恢復增長，這將是我們關注的一個關鍵領域。

So moving to Slide 9. From a pipeline and innovation standpoint, it was a busy quarter. You're well aware of the approval of Entresto in patients with a below-normal left ventricular ejection fraction, updates to Cosentyx label and approvals in Kesimpta.

所以轉到幻燈片 9。從管道和創新的角度來看，這是一個繁忙的季度。您很清楚 Entresto 在左心室射血分數低於正常值的患者中的批准、對 Cosentyx 標籤的更新以及在 Kesimpta 的批准。

In terms of readouts, the VISION study read out positive on both PFS -- rPFS as well as on overall survival. And we look forward to presenting that impressive data in an upcoming medical congress. We had the positive readout of Cosentyx in juvenile idiopathic arthritis, which we now are moving towards filing and will continue to enable us to expand Cosentyx indication, where we have a goal of getting to 9 indications or formulations to enable Cosentyx to continue to drive dynamic growth over this decade.

在讀數方面，VISION 研究在 PFS - rPFS 以及總體存活率方面均顯示為陽性。我們期待在即將召開的醫學大會上展示這些令人印象深刻的數據。我們在幼年特發性關節炎中獲得了 Cosentyx 的積極讀數，我們現在正著手提交並將繼續使我們能夠擴大 Cosentyx 適應症，我們的目標是達到 9 種適應症或配方，使 Cosentyx 能夠繼續推動動態這十年的增長。

LNP, iptacopan, had a positive readout in IgA nephropathy, and we'll look forward to presenting that data in an upcoming congress, and we have already initiated the Phase III program. You'll remember that IgA nephropathy is one of the larger indications we have for this medicine. We also had the positive readout, which we've already stated in PNH, and the phase III started there. And we're expecting additional readouts, which I'll talk about in a moment.

LNP iptacopan 在 IgA 腎病中的讀數呈陽性，我們期待在即將召開的大會上展示該數據，我們已經啟動了 III 期計劃。您會記得 IgA 腎病是我們對這種藥物的較大適應症之一。我們也有正面的讀數，我們已經在 PNH 中說明了這一點，並且第三階段從那裡開始。我們期待更多的讀數，我稍後會談到。

We did have the results of Entresto in the post-AMI setting, where it had a high hurdle, trying to demonstrate superiority to ramipril in a very fragile patient population. These are patients who have recently had a myocardial infarction. Entresto had a consistent positive trend across all the primary and secondary end points, but did not meet statistical significance for superiority. It did demonstrate a very strong safety profile, and we'll look forward to discussing the data further with regulators in the months to come. And lastly, you're aware of the canakinumab second-line readout.

我們確實在 AMI 後環境中獲得了 Entresto 的結果，它有一個很高的障礙，試圖在非常脆弱的患者群體中證明其優於雷米普利。這些是最近患有心肌梗塞的患者。 Entresto 在所有主要和次要終點都有一致的積極趨勢，但沒有達到統計學上的優勢。它確實展示了非常強大的安全性，我們期待在未來幾個月與監管機構進一步討論數據。最後，您知道 canakinumab 二線讀數。

So some other designations and submissions on the bottom of the slide, but I'd like to move to the next slide and take a little bit of time to go through some of the updates on our expected milestones across our key programs in life cycle management, Pharmaceuticals and Oncology. I already mentioned the Entresto and Cosentyx information. On Cosentyx, we are on track for the hidradenitis suppurativa Phase III readout in the second half of 2021.

幻燈片底部還有一些其他的名稱和意見，但我想轉到下一張幻燈片，花一點時間來了解我們在生命週期管理的關鍵項目中的預期里程碑的一些更新、藥物和腫瘤學。我已經提到了 Entresto 和 Cosentyx 信息。在 Cosentyx 上，我們有望在 2021 年下半年進行化膿性汗腺炎 III 期讀數。

In Kisqali, importantly, we have completed enrollment of the adjuvant study in medium- and high-risk patients, and Susanne will say a bit more about that, but a readout in 2022.

在 Kisqali，重要的是，我們已經完成了對中高風險患者的輔助研究的招募，Susanne 會對此多說一些，但會在 2022 年公佈。

With respect to Leqvio we remain on track for a CRL response to be submitted in the Q2, Q3 time frame. We've also completed a tech transfer into our Schaftenau facility at our -- in Austria and are evaluating the best way to submit that response now with the FDA. And I think those are some of the key highlights on life cycle management.

對於 Leqvio，我們將繼續按計劃在第二季度和第三季度提交 CRL 響應。我們還完成了一項技術轉移到我們位於奧地利的 Schaftenau 工廠，並正在評估現在向 FDA 提交該響應的最佳方式。我認為這些是生命週期管理的一些關鍵亮點。

Now turning to Pharmaceuticals, the portfolio. I've already mentioned on LNP023 some of the key milestones. But I think the key thing here is that we're continuing to rapidly move across a broad range of indications into Phase III.

現在轉向藥物組合。我已經在 LNP023 上提到了一些關鍵的里程碑。但我認為這裡的關鍵是我們正在繼續快速進入第三階段。

The other highlight I wanted to mention is branaplam, where we have completed the Phase I study, and we look forward to providing that information in an upcoming medical congress. We have also completed discussions with the regulators to finalize the Phase IIb study design and plan to start that study in the second half of 2021.

我想提到的另一個亮點是 branaplam，我們已經完成了第一階段的研究，我們期待在即將舉行的醫學大會上提供這些信息。我們還完成了與監管機構的討論，以最終確定 IIb 期研究設計，併計劃在 2021 年下半年開始該研究。

And then moving to Oncology. I think very important, the canakinumab studies remain on track in first line and adjuvant. But as important in many ways now, the Lu-PSMA studies in the early lines of therapy in hormone-sensitive prostate cancer is -- have begun, and we look forward to enrolling those studies rapidly with a planned readout in 2024.

然後轉到腫瘤學。我認為非常重要的是，canakinumab 的研究在一線和輔助治療方面仍處於正軌。但現在在許多方面同樣重要的是，在激素敏感性前列腺癌的早期治療線中的 Lu-PSMA 研究已經開始，我們期待著在 2024 年迅速招募這些研究併計劃讀出。

Now moving to the next slide. You probably will have seen that we've completed our in-licensing agreement for tislelizumab with BeiGene. And we did have the readout of 2 important readout -- studies that will enable submissions over the course of this year, first- and second-line non-small cell lung cancer at AACR. You can see the data here on the right with solid overall survival data.

現在轉到下一張幻燈片。您可能已經看到，我們已經與百濟神州完成了 tislelizumab 的許可協議。我們確實獲得了 2 個重要讀數的讀數——將在今年提交的研究，AACR 的一線和二線非小細胞肺癌。您可以在右側看到數據，其中包含可靠的總體生存數據。

And then also in esophageal cancer, where the studies have met its primary end point, prolonging OSs versus chemo. And we'll provide that data release as well in an upcoming congress. So these studies will enable ex-China filings, which are on track for 2021. And we have 15 potential registration-enabling studies ongoing as well as a broad range of combination studies in the program.

然後在食道癌中，研究已經達到其主要終點，與化療相比延長了 OS。我們還將在即將召開的大會上提供該數據發布。因此，這些研究將使中國以外的申請成為可能，這些申請有望在 2021 年進行。我們正在進行 15 項潛在的註冊授權研究，以及該計劃中的廣泛組合研究。

Now moving to the next slide. I wanted to close just by noting our commitment across the company in areas of high materiality for Novartis to advance our efforts in ESG and returning -- and building trust with society. I mentioned the ranking we have now in Sustainalytics. We're the only company amongst our peer set now ranked with a low risk in the Sustainalytics ranking.

現在轉到下一張幻燈片。最後，我想通過指出我們在整個公司對諾華（Novartis）高重要性領域的承諾來推進我們在 ESG 和回報方面的努力——以及與社會建立信任。我提到了我們現在在 Sustainalytics 中的排名。我們是同行中唯一一家在 Sustainalytics 排名中風險較低的公司。

Also in Access to Medicines Index, a #2 ranking. But we were very proud of our #1 ranking in product delivery, our ability to bring our innovative medicines to patients most to need in low and low and middle income countries. Other highlights include an agreement with Bill & Melinda Gates Foundation on bringing transformative therapies to patients in sickle cell disease as well as being included in the Bloomberg Gender-Equality Index. And of course, you're aware of our ongoing efforts in COVID-19 to provide our manufacturing capacity as well as to collaborate with molecular partners as well as our own in-house oral program for a pan-COVID oral protease inhibitor to hopefully bring therapeutics over time to help with the long-term control of COVID-19.

同樣在獲得藥品指數中，排名第二。但我們對我們在產品交付方面的排名第一感到非常自豪，我們有能力將我們的創新藥物帶給中低收入國家最需要的患者。其他亮點包括與比爾和梅琳達蓋茨基金會就為鐮狀細胞病患者提供變革性療法以及被納入彭博性別平等指數的協議。當然，您知道我們在 COVID-19 方面的持續努力，以提供我們的製造能力，並與分子合作夥伴合作，以及我們自己的內部口服計劃，希望能帶來泛 COVID 口服蛋白酶抑製劑隨著時間的推移，治療有助於長期控制 COVID-19。

So that gives you a little bit of an overview. And I'd like to hand it over now to Marie-France to dive a little bit deeper into Pharmaceuticals. Marie-France?

因此，這為您提供了一些概述。我現在想把它交給 Marie-France 來更深入地研究製藥業。瑪麗-法蘭西？

Thank you, Vas. Good morning, good afternoon. I'm pleased to update you on our Q1 performance for pharma. We had revenues of $6.3 billion this quarter, And while the overall growth rate was affected versus Q1 2020, our growth drivers and launches are showing excellent momentum with 23% growth versus prior year. What is noteworthy is that half of our revenues are now coming from our growth drivers and launches. This is a result of clear portfolio prioritization and a relentless focus on commercial execution. We've also doubled down on early launch preparation and our investments reflect that.

謝謝你，瓦斯。早上好，下午好。我很高興向您介紹我們第一季度製藥業的表現。我們本季度的收入為 63 億美元，雖然與 2020 年第一季度相比，整體增長率受到了影響，但我們的增長動力和發布表現出極好的勢頭，與去年相比增長了 23%。值得注意的是，我們現在一半的收入來自我們的增長動力和發布。這是明確的投資組合優先級和對商業執行的不懈關注的結果。我們還在早期發布準備方面加倍投入，我們的投資反映了這一點。

If we move to Slide 15, Cosentyx, our largest brand, delivered double-digit growth. As we said in Q4, we've seen an access change in one U.S. account, which has impacted volume. Although the shares were affected, we will continue to deliver double-digit growth in the U.S. based on the rebate upside realized and the volume growth over time. Our overall access remains strong in the U.S. and continues to be a key pillar of our strategy.

如果我們轉到幻燈片 15，我們最大的品牌 Cosentyx 實現了兩位數的增長。正如我們在第四季度所說，我們看到一個美國賬戶的訪問權限發生了變化，這影響了交易量。儘管股價受到影響，但我們將繼續在美國實現兩位數的增長，這取決於實現的回扣上行空間和隨著時間的推移的銷量增長。我們在美國的整體訪問能力仍然很強，並且仍然是我們戰略的關鍵支柱。

The other constant is that customers continue to experience Cosentyx as a tried and trusted complete treatment. Now that the shares have adjusted to the new access levels, we are back to our position that we will grow with the market in dermatology and outgrow the market in rheumatology.

另一個不變的是，客戶繼續體驗 Cosentyx 作為一種久經考驗且值得信賴的完整治療方法。既然股票已經調整到新的准入水平，我們又回到了我們將與皮膚病學市場一起成長並超越風濕病學市場的立場。

Ex U.S., our focus is on accelerating volume growth. We're off to a great start in China following our NRDL listing in March. In Europe, Cosentyx continues to be the leading originator biologic across all 3 indications. As we bring the newer indications to market, we expect some pricing concessions in Europe, and that will only further enable volume-driven growth. Full year, we're confident that the Cosentyx team can deliver double-digit growth based on our strategic pillars: focus on strong access globally, geographic expansion and our leading industry approach to data. Beyond 2021, our ambitious life cycle program provides further upside opportunities for the future.

除美國外，我們的重點是加速銷量增長。繼 3 月 NRDL 上市後，我們在中國有了一個良好的開端。在歐洲， Cosentyx 繼續是所有 3 種適應症的領先生物製劑。隨著我們將新的跡象推向市場，我們預計歐洲會出現一些定價讓步，而這只會進一步推動銷量驅動的增長。全年，我們相信 Cosentyx 團隊可以基於我們的戰略支柱實現兩位數的增長：專注於強大的全球訪問、地理擴張和我們領先的行業數據方法。 2021 年之後，我們雄心勃勃的生命週期計劃為未來提供了進一步的上行機會。

Slide 16. The Entresto is doing extremely well with strong growth across the globe. In the U.S., we're seeing a convergence of events. Physicians are adopting the ACC Expert Consensus recommendations for Entresto in first line. We're seeing recovery from COVID and enthusiasm around the expanded indication. It's great to see the growing confidence to go direct to ARNI, which is reflective of the strong evidence behind Entresto.

幻燈片 16。Entresto 在全球範圍內的強勁增長表現非常出色。在美國，我們看到了事件的趨同。醫生在一線採用 ACC 專家共識建議 Entresto。我們看到了 COVID 的複蘇以及對擴大適應症的熱情。很高興看到直接使用 ARNI 的信心越來越大，這反映了 Entresto 背後的有力證據。

We're seeing all-time highs in NBRxs. The label in the U.S. now covers 5 out of 6 patients with chronic heart failure, and this makes it easy for physicians to initiate appropriate patients. We now estimate that about 3.2 million patients are being treated with Entresto today. This is a big achievement and is testament to the exquisite execution of the teams in the field.

我們看到 NBRxs 的歷史新高。在美國，該標籤現在涵蓋了 6 名慢性心力衰竭患者中的 5 名，這使得醫生可以輕鬆找到合適的患者。我們現在估計，今天約有 320 萬患者正在接受 Entresto 治療。這是一項了不起的成就，也證明了該領域團隊的精湛執行力。

We now have 30% share of the HFrEF patients in the U.S., so there remains significant room to grow as 70% of rEF patients are still on prior standard of care. And we've only just started to promote in the pEF population.

我們現在在美國擁有 30% 的 HFrEF 患者份額，因此仍有很大的增長空間，因為 70% 的 rEF 患者仍在接受先前的護理標準。我們才剛剛開始在 pEF 人群中進行推廣。

If I move to Slide 17, Zolgensma had a strong quarter, which was driven by reimbursement wins in a number of European markets, while the U.S. continued its steady trend. As every new country initially adds a bolus of patients and then moves into a steady state, you can expect to see some volatility in the quarterly sales pattern. We have new compelling data on Zolgensma's efficacy in presymptomatic patients. We're also initiating a new Phase III trial, called SMART, to strengthen the confidence for children up to 21 kilograms in the EU.

如果我轉到第 17 張幻燈片，Zolgensma 的季度表現強勁，這是由許多歐洲市場的報銷勝利推動的，而美國則繼續保持穩定的趨勢。由於每個新國家最初都會增加一批患者，然後進入穩定狀態，因此您可以預期季度銷售模式會出現一些波動。我們有關於 Zolgensma 對症狀前患者療效的令人信服的新數據。我們還啟動了一項名為 SMART 的新 III 期試驗，以增強歐盟 21 公斤以下兒童的信心。

We're on track with our preclinical studies for the IT formulation, which would also allow us to bring Zolgensma to older children. Our 5-year durability data confirms what is -- this medicine can offer in 1 single treatment. And this is what really sets Zolgensma apart and why we are relentlessly progressing our gene therapy agenda with 2 more INDs planned this year.

我們正在對 IT 製劑進行臨床前研究，這也將使我們能夠將 Zolgensma 帶給年齡較大的兒童。我們的 5 年耐用性數據證實了這一點——這種藥物可以在 1 次單一治療中提供。這就是真正讓 Zolgensma 與眾不同的原因，也是為什麼我們正在不懈地推進我們的基因治療議程，今年計劃再進行 2 項 IND。

If we move to Slide 18. With Kesimpta, we're bringing a high-efficacy B-cell therapy to patients early in their disease. Our new PIRA data builds on the strong efficacy profile already shown in our pivotal trials. Kesimpta can reduce disease progression that happens independent of relapses by up to 60% when used early. We believe this is incredibly meaningful data for patients because PIRA actually accounts for the majority of progression. This data is unique in this early patient population.

如果我們轉到幻燈片 18。有了 Kesimpta，我們將為處於疾病早期的患者帶來高效的 B 細胞療法。我們的新 PIRA 數據建立在我們的關鍵試驗中已經顯示的強大功效概況之上。早期使用 Kesimpta 可以將與復發無關的疾病進展減少多達 60%。我們相信這對患者來說是非常有意義的數據，因為 PIRA 實際上佔進展的大部分。該數據在這一早期患者群體中是獨一無二的。

While the pandemic is still impacting the dynamic market and the prescribing behavior, all the metrics that are in our control are tracking positively. We're seeing more than 50% use in first line for switch, which is exactly aligned to our value proposition. The team has also done a great job on access. In fact, the conversion from free to paid product is ahead of plan. This is reflected in the Q1 numbers, which also include a $9 million revenue adjustment relating to Q4 2020 and why we now expect 65% of sales in the second half of the year.

儘管大流行仍在影響動態市場和處方行為，但我們控制的所有指標都在積極跟踪。我們看到超過 50% 的交換機用於第一行，這與我們的價值主張完全一致。該團隊在訪問方面也做得很好。事實上，從免費產品到付費產品的轉變是超前的。這反映在第一季度的數據中，其中還包括與 2020 年第四季度相關的 900 萬美元的收入調整，以及我們現在預計下半年銷售額的 65% 的原因。

Recent data also shows that the IgG levels of patients on Kesimpta are maintained over time, which is important to fight infections including COVID and reinforces our safety profile. Once the market bounces back, we expect strong uptake for this product based on the compelling product profile, and the growing evidence base behind the brand.

最近的數據還顯示， Kesimpta 患者的 IgG 水平隨著時間的推移而保持不變，這對於對抗包括 COVID 在內的感染很重要，並加強了我們的安全性。一旦市場反彈，我們預計基於引人注目的產品簡介和品牌背後不斷增長的證據基礎，該產品將被強勁吸收。

Remember that we designed this brand specifically for multiple sclerosis. As you can see from the data, we are achieving sustained depletion with a monthly dosing, and we're not seeing a rebound between doses. With the high and sustained efficacy and the opportunity for at-home treatment, Kesimpta has what it takes to fundamentally change how we treat multiple sclerosis.

請記住，我們專門為多發性硬化症設計了這個品牌。正如您從數據中看到的那樣，我們正在通過每月給藥實現持續消耗，並且我們沒有看到劑量之間的反彈。憑藉高效和持續的療效以及在家治療的機會，Kesimpta 擁有從根本上改變我們治療多發性硬化症的方法。

Slide 19. Leqvio was launched in Germany and Austria in February in a limited population of patients at very high cardiovascular risk. Physicians seem happy with the immediate drop they see in LDL-C levels and with the ability to have the sustained effect with only 2 injections per year.

Slide 19. Leqvio 於 2 月在德國和奧地利推出，用於心血管風險極高的有限患者。醫生們似乎對他們看到的 LDL-C 水平的立即下降感到滿意，並且每年只需注射 2 次就能產生持續的效果。

In Europe, we need the outcomes data, which we expect in 2026. So in the meantime, we want to advance discussions on population health approaches as our goal is to bring this medicine to a broad population as quickly as possible, and this way, significantly lower the burden of ASCVD on patients and systems. The U.K. NHS agreement is our first such agreement and is on track for launch in Q3. More to come.

在歐洲，我們需要我們預計在 2026 年獲得的結果數據。因此，與此同時，我們希望推進關於人口健康方法的討論，因為我們的目標是盡快將這種藥物帶給廣大人群，這樣，顯著降低 ASCVD 對患者和系統的負擔。英國 NHS 協議是我們的第一個此類協議，並有望在第三季度推出。更多即將到來。

In the U.S., we're on track to resubmit our filing in Q2, Q3. While we're preparing our filing, we're also actively engaging with a large number of U.S. health care systems to lay the foundation for broad uptake.

在美國，我們有望在第二季度和第三季度重新提交我們的申請。在我們準備申報的同時，我們也在積極與大量美國醫療保健系統合作，為廣泛採用奠定基礎。

In summary, we continue to focus on executing our strategy, maximizing our growth drivers, delivering our launches, preparing our next big bets. Our growth drivers are doing very well. Our launches are gaining momentum, and now these accounts for half our sales. As we see a more dynamic market environment, we'll continue to accelerate our portfolio shift and double down on patient, HCP and health care system engagement in order to enable access to more patients faster. I want to thank the teams around the world who worked so hard to achieve this every day.

總之，我們將繼續專注於執行我們的戰略，最大化我們的增長動力，交付我們的產品，準備我們的下一個大賭注。我們的增長動力做得很好。我們的產品發布勢頭強勁，現在這些產品占我們銷售額的一半。隨著我們看到一個更加動態的市場環境，我們將繼續加快我們的產品組合轉變，並加倍加強患者、HCP 和醫療保健系統的參與，以便更快地獲得更多患者。我要感謝每天為實現這一目標而努力工作的世界各地的團隊。

Over to Susanne.

交給蘇珊。

Thank you, Marie-France. So let's move to Slide 21. Our Oncology business has delivered solid performance in the first quarter with net sales of $3.8 billion, broadly in line with previous year. Our key growth drivers continue to perform well, including Kymriah, Kisqali, Promacta/Revolade and Jakavi.

謝謝你，瑪麗-法蘭西。因此，讓我們轉到幻燈片 21。我們的腫瘤業務在第一季度取得了穩健的業績，淨銷售額為 38 億美元，與去年基本持平。我們的主要增長動力繼續表現良好，包括 Kymriah、Kisqali、Promacta/Revolade 和 Jakavi。

Both our growth brands and recent launches together grew 15% versus previous year and contributed to almost half of the overall Oncology sales. allowing us to more than compensate for the continued generic erosion of Afinitor and Exjade/Jadenu in the U.S. and Sandostatin LAR in the EU.

我們的成長型品牌和近期推出的產品與去年相比增長了 15%，佔腫瘤學總銷售額的近一半。使我們能夠補償美國 Afinitor 和 Exjade/Jadenu 以及歐盟 Sandostatin LAR 的持續通用侵蝕。

The first quarter was marked by the continued impact of the pandemic on certain segments of our portfolio with a more pronounced effect on hospital-initiated therapies, our breast cancer portfolio and recent launches. Due to the pandemic, patients did not see their physicians at the same frequency, and diagnosis and treatment initiations remained below pre-pandemic levels. However, we remain confident that patient visits to hospitals will resume and treatment patterns will normalize, leading to acceleration of growth in these segments.

第一季度的特點是大流行對我們產品組合的某些部分的持續影響，對醫院啟動的療法、我們的乳腺癌產品組合和最近推出的產品產生了更明顯的影響。由於大流行，患者看醫生的頻率不同，診斷和治療開始率仍低於大流行前的水平。然而，我們仍然相信患者到醫院就診將恢復，治療模式將正常化，從而加速這些領域的增長。

Moving to Slide 22. Just to remind you that we are the only pharmaceutical company which is pursuing 4 different cancer treatment platforms. These include radioligand therapy, cell and gene therapy, targeted therapy and immunotherapy with an opportunity to combine these platforms for better outcomes.

轉到幻燈片 22。提醒您，我們是唯一一家追求 4 種不同癌症治療平台的製藥公司。這些包括放射配體療法、細胞和基因療法、靶向療法和免疫療法，並有機會將這些平台結合起來以獲得更好的結果。

Today, I wanted to especially reflect on our progress with radioligand therapies. Since the acquisition of AAA in 2018, we have established strong global expertise in commercializing radioligand therapies supported by a specialized supply chain, manufacturing capabilities across 4 radioligand therapy production sites.

今天，我想特別回顧一下我們在放射配體療法方面取得的進展。自 2018 年收購 AAA 以來，我們在放射配體療法商業化方面建立了強大的全球專業知識，並得到了專業供應鏈的支持，並在 4 個放射配體療法生產基地擁有製造能力。

With Lutathera, our radioligand therapy for neuroendocrine tumors, we have gained a lot of momentum. And in partnership with now 400 centers, we are able to deliver this life-saving treatment to more than 9,000 patients since launch. We have generated a unique skill set and experience in manufacturing, supply and commercialization of radioligand therapies. And we will leverage these to maximize the potential of our future launches in this space.

Lutathera 是我們用於神經內分泌腫瘤的放射配體療法，我們獲得了很大的動力。自推出以來，我們與現在 400 個中心合作，能夠為 9,000 多名患者提供這種挽救生命的治療。我們在放射配體療法的製造、供應和商業化方面產生了獨特的技能和經驗。我們將利用這些來最大限度地發揮我們未來在該領域推出的潛力。

On the development side, we are advancing 4 clinical programs and around 11 preclinical and discovery programs to identify the next wave of radioligand therapies for cancer. We continue to invest in our radioligand pipeline through the in-licenses of a library of fibroblast activating protein, or FAP, targeting agents. The investment into Aktis Oncology for development of alpha-based radioligand therapies and our most recent collaboration with Artios Pharma to discover and identify novel combinations of DNA Damage Response inhibitors with RLTs.

在開發方面，我們正在推進 4 個臨床項目和大約 11 個臨床前和發現項目，以確定下一波癌症放射配體療法。我們通過成纖維細胞激活蛋白或 FAP 靶向劑庫的許可繼續投資於我們的放射性配體管道。對 Aktis Oncology 的投資以開發基於 α 的放射性配體療法，以及我們最近與 Artios Pharma 的合作，以發現和識別 DNA 損傷反應抑製劑與 RLT 的新組合。

Moving to Slide 23. Earlier in March, we were excited to share with you data from the VISION study with lutetium -PSMA in metastatic, castration-resistant prostate cancer. And the trial met both primary end points of improved overall survival and radiographic progression-free survival versus standard of care.

轉到幻燈片 23。3 月初，我們很高興與您分享 VISION 研究的數據，該研究使用镥-PSMA 治療轉移性、去勢抵抗性前列腺癌。並且該試驗達到了改善總生存期和影像學無進展生存期與護理標準相比的主要終點。

Just to remind you, prostate cancer is the second most diagnosed cancer globally. And in the majority of cases, patients unfortunately develop metastases by the time of castration-resistant prostate cancer diagnosis. There is significant unmet medical need in this population with a 5-year survival rate of approximately 15%, and there are very limited treatment options.

提醒您一下，前列腺癌是全球第二大確診癌症。在大多數情況下，不幸的是，患者在診斷出去勢抵抗性前列腺癌時會發生轉移。該人群存在大量未滿足的醫療需求，5 年生存率約為 15%，治療選擇非常有限。

The VISION study findings confirm that lutetium-PSMA has the potential to become the targeted treatment for more than 80% of men with late-stage advanced prostate cancer. We intend to initiate discussions with regulatory authorities and prepare submissions to the FDA and EMA by the end of this year.

VISION 研究結果證實，镥-PSMA 有可能成為超過 80% 的晚期晚期前列腺癌男性的靶向治療。我們打算在今年年底前與監管機構展開討論，並準備向 FDA 和 EMA 提交文件。

On the commercial side, we are effectively preparing for the upcoming launch with a focus on hospital and community centers. More than 70% of prostate cancer patients are treated here.

在商業方面，我們正在有效地為即將推出的產品做準備，重點是醫院和社區中心。超過 70% 的前列腺癌患者在這裡接受治療。

Given the prevalence of the disease, we are working with treatment centers to better understand their operational needs for capacity expansion in order to administer targeted radioligand therapies. Additionally, we are raising awareness on the clinical relevance of PSMA and the potential value of targeted RLTs as a new mechanism of action in advanced prostate cancer.

鑑於這種疾病的普遍性，我們正在與治療中心合作，以更好地了解他們對產能擴張的運營需求，以便進行有針對性的放射配體治療。此外，我們正在提高人們對 PSMA 的臨床相關性以及靶向 RLT 作為晚期前列腺癌新作用機制的潛在價值的認識。

On the development side, the VISION trial findings are supporting our confidence in moving into earlier lines of advanced prostate cancer. We are planning a Phase III study with lutetium-PSMA in the pre-taxane, metastatic, castration-resistant prostate cancer setting and in the metastatic hormone-sensitive setting. We anticipate that both of these studies will start in the first half of 2021.

在開發方面，VISION 試驗結果支持我們對進入晚期前列腺癌早期線的信心。我們正計劃在紫杉烷前、轉移性、去勢抵抗性前列腺癌環境和轉移性激素敏感環境中使用镥-PSMA 進行 III 期研究。我們預計這兩項研究都將在 2021 年上半年開始。

Moving to Slide 24. Kisqali delivered solid performance in the first quarter with sales up 19%, reaching $195 million, driven by unprecedented overall survival benefit from 2 pivotal Phase III trials. We are very pleased to see Kisqali continued to grow strongly and gaining market share ex U.S. especially on European markets.

轉到幻燈片 24。 Kisqali 在第一季度實現了穩健的業績，銷售額增長了 19%，達到 1.95 億美元，這得益於 2 項關鍵 III 期試驗帶來的前所未有的總體生存收益。我們很高興看到 Kisqali 繼續強勁增長並獲得除美國以外的市場份額，尤其是在歐洲市場。

In the U.S., Kisqali maintained share despite the overall slowdown of the CDK4/6 market, driven by the suppressed diagnostics rate and overall decrease in new patient starts. We believe Kisqali has a unique profile supported by the longest reported median OS among all Phase III trials in advanced breast cancer, reaching around 5 years in premenopausal patients. Therefore, we remain confident in the longer-term potential of Kisqali.

在美國，儘管 CDK4/6 市場總體放緩，但由於診斷率受到抑制和新患者開始總體下降，Kisqali 仍保持份額。我們相信 Kisqali 具有獨特的特徵，在所有晚期乳腺癌 III 期試驗中報告的中位 OS 最長，在絕經前患者中達到約 5 年。因此，我們對 Kisqali 的長期潛力充滿信心。

On the development side, NATALEE adjuvant study in intermediate and high-risk populations has completed enrollment ahead of plan, and we are on track for final readout in 2022. So overall, we are confident with Kisqali resilient performance in what continues to be a challenging market environment.

在開發方面，針對中高風險人群的 NATALEE 輔助研究已提前完成註冊，我們有望在 2022 年進行最終讀數。因此，總體而言，我們對 Kisqali 的彈性表現充滿信心，這仍然是一個挑戰市場環境。

And with that, let me hand over to Harry.

有了這個，讓我交給哈利。

Yes. Thank you, Susanne. Good morning, and good afternoon, everyone. I'm now going to walk you through some of the financials for the first quarter as well as provide you with an update on our '21 guidance. As always, my comments refer to growth rates in constant currencies, unless otherwise noted.

是的。謝謝你，蘇珊。大家早上好，下午好。我現在將向您介紹第一季度的一些財務狀況，並為您提供我們 21 年指導的最新信息。與往常一樣，除非另有說明，否則我的評論指的是固定貨幣增長率。

So Slide 26 shows the summary of our operational performance for the first quarter. As we indicated at the start of the year, quarter 1 growth was negatively impacted by prior year quarter 1 forward purchasing, which amounted to around minus 3 points on sales and minus 7 points on core operating income. This quarter also still had continued demand impact from COVID-19, particularly in dermatology, ophthalmology, our breast cancer portfolio and for the Sandoz retail and anti-infectives businesses. Free cash flow was impacted this quarter by the $650 million upfront payment for tislelizumab in-licensing from BeiGene. I will give more detail about free cash flow later in the presentation. With these caveats, you can see the changes in net sales and core operating income, minus 2 points and minus 8 points, respectively, which flowed down into EPS and free cash flow.

因此，幻燈片 26 顯示了我們第一季度的運營業績摘要。正如我們在年初指出的那樣，第一季度的增長受到上一年第一季度遠期採購的負面影響，銷售額約為負 3 個百分點，核心營業收入為負 7 個百分點。本季度 COVID-19 仍對需求產生持續影響，特別是在皮膚科、眼科、我們的乳腺癌產品組合以及山德士零售和抗感染業務方面。本季度自由現金流受到百濟神州 tislelizumab 6.5 億美元預付款的影響。我將在演示文稿的後面部分詳細介紹自由現金流。有了這些警告，您可以看到淨銷售額和核心營業收入的變化分別為負 2 點和負 8 點，這些變化流入了每股收益和自由現金流。

Turning to Slide 27. We have shown the change versus prior year for sales, core operating income and core margins in the first quarter as reported on the left-hand side of this table. On the right-hand side, as we did similar chart last year quarter 1, we have illustrated what the underlying operational performance looks like if we excluded the prior year forward purchasing. Innovative Medicines had a solid underlying performance. Sales grew plus 3%; core operating income, plus 6%; and core margin was up plus 1% point. Innovative Medicines performance was driven by continued strong double-digit growth of our key growth drivers, like Entresto, Zolgensma, Cosentyx, and our Oncology growth drivers, partly offset by mature product declines and generic erosion.

轉到幻燈片 27。我們已經顯示了第一季度銷售額、核心營業收入和核心利潤率與上一年相比的變化，如本表左側所示。在右側，正如我們在去年第一季度所做的類似圖表一樣，我們已經說明瞭如果我們排除了上一年的遠期採購，潛在的運營績效會是什麼樣子。創新藥物的潛在表現穩健。銷售額增長了 3%；核心營業收入，加6%；核心利潤率上升 1%。創新藥物的業績受到我們關鍵增長驅動因素（如 Entresto、Zolgensma、Cosentyx）和我們的腫瘤學增長驅動因素持續強勁兩位數增長的推動，部分被成熟產品下降和仿製藥侵蝕所抵消。

For Sandoz, we would still have seen a challenging quarter. Excluding prior year forward purchasing, Sandoz sales were still down minus 9% and core operating income was down minus 29%. As Vas explained earlier, some of the key challenges for Sandoz were the pricing impact and historically low cough and cold season and softer retail demand as a result of COVID. At the group level, underlying performance added up to plus 1% of sales, and core operating income declined minus 1%.

對於山德士來說，我們仍然會看到一個充滿挑戰的季度。不包括上一年的遠期採購，山德士的銷售額仍然下降了-9%，核心營業收入下降了-29%。正如 Vas 之前解釋的那樣，山德士面臨的一些主要挑戰是價格影響、咳嗽和感冒季節的歷史低位以及 COVID 導致的零售需求疲軟。在集團層面，基本業績加起來佔銷售額的 1%，核心營業收入下降了負 1%。

Let's now go to Slide 28. One way of better understanding underlying performance given the distortions caused by COVID over the last year is to compare to what you could call a normal first quarter in 2019 with the quarter 1 2021. On this slide, we have shown what happens to group and Innovative Medicines over the last 3 quarter 1s for both top and bottom line. We show the CAGR for both, and you can see that for group sales, CAGR was a solid plus 5% and core operating income CAGR was plus 11%. This is clearly driven by Innovative Medicines with the top line growing at a 7% CAGR and the bottom line even at 13% CAGR, which shows the strong operational performance of our Innovative Medicines division. Innovative Medicines' core margin increased by 300 basis points over the 2 years, which is the result of our good top line growth, combined with very good progress on productivity programs.

現在讓我們轉到幻燈片 28。鑑於去年 COVID 造成的扭曲，更好地理解潛在績效的一種方法是將 2019 年第一季度的正常情況與 2021 年第一季度進行比較。在這張幻燈片上，我們有顯示了過去 3 個季度 1 中集團和創新藥物的頂線和底線發生了什麼。我們展示了兩者的複合年增長率，你可以看到，對於集團銷售，複合年增長率是穩定的 5%，核心營業收入的複合年增長率是 11%。這顯然是由創新藥物推動的，收入以 7% 的複合年增長率增長，底線甚至以 13% 的複合年增長率增長，這表明我們創新藥物部門的強勁運營業績。創新藥物的核心利潤率在 2 年內增加了 300 個基點，這是我們良好的收入增長以及生產力計劃取得非常好的進展的結果。

On Slide 29, you can see that free cash flow for the quarter was $1.6 billion. The most significant reason, as mentioned, for this decrease was the USD 650 million upfront payment to in-license tislelizumab from BeiGene and lower operating income adjusted for noncash items, partly offset by favorable changes in working capital.

在幻燈片 29 上，您可以看到本季度的自由現金流為 16 億美元。如前所述，最重要的原因是百濟神州向許可 tislelizumab 支付了 6.5 億美元的預付款以及根據非現金項目調整後的營業收入下降，部分被營運資金的有利變化所抵消。

Now turning to our full year 2021 guidance on Slide 30. We confirm full year guidance, both for group and Innovative Medicines for sales and core operating income. For Innovative Medicines, we continue to expect mid-single-digit sales growth in 2021. For Sandoz, reflecting the start of the year, we now expect sales to decline low to mid-single digit revised downwards from the prior broadly in line guidance for Sandoz.

現在轉向我們在幻燈片 30 上的 2021 年全年指導。我們確認全年指導，包括集團和創新藥物的銷售和核心營業收入。對於創新藥物，我們繼續預計 2021 年銷售額將實現中個位數增長。對於山德士，反映今年年初，我們現在預計銷售額將下降至中個位數，從之前大致一致的指導下調山德士。

Now as an exception to our regular guidance format and due to the impact COVID had on Sandoz quarter 1 results, we are also going to provide for this year the breakdown of core operating income guidance by division. We expect Innovative Medicines' core operating income to grow mid- to high single digits ahead of sales. And for Sandoz, we expect core operating income to decline low to mid-teens. The key assumption for this guidance remains that we see a return to normal global health care systems and prescribing dynamics by mid of 2021. And in addition, we continue to assume that no Gilenya and no Sandostatin LAR generics enter in 2021 in the U.S.

現在，作為我們常規指導格式的一個例外，並且由於 COVID 對 Sandoz 第一季度業績的影響，我們還將提供今年按部門劃分的核心營業收入指導明細。我們預計創新藥物的核心營業收入將在銷售之前增長中高個位數。對於山德士，我們預計核心營業收入將下降到十幾歲左右。該指南的關鍵假設仍然是，我們將看到到 2021 年年中恢復正常的全球醫療保健系統和處方動態。此外，我們繼續假設 Gilenya 和 Sandostatin LAR 仿製藥在 2021 年不會進入美國。

Turning now to my last slide. Several of you asked for a bit more detail on quarterly phasing. On Slide 31, I've tried to explain the dynamics that we expect to see in quarter 2 and for the full year, given the impact on COVID -- of COVID, both in 2020 and '21. As you recall, at the start of the year, we guided to expect quarter 1 sales to decline low to mid-single digits, and underlying sales, excluding prior year forward purchasing, to be broadly in line with prior year. This was the case and as already explained, sales, excluding prior year forward purchasing grew plus 1% in quarter 1.

現在轉到我的最後一張幻燈片。你們中的一些人要求提供有關季度分階段的更多細節。在幻燈片 31 上，鑑於 2020 年和 21 年對 COVID 的影響，我試圖解釋我們預計在第二季度和全年看到的動態。您還記得，在今年年初，我們預計第一季度的銷售額將下降到中個位數，而基礎銷售額（不包括上一年的遠期採購）將與上一年大體保持一致。情況確實如此，正如已經解釋的那樣，第一季度銷售額（不包括上一年的遠期採購）增長了 1%。

For quarter 2, we expect sales to grow mid-single digits, benefiting from approximately plus 3% points of prior year forward purchasing reversal. For core operating income, in the first half of 2021, we expect it to decline low single digits due to prior year lower cost base and investments in quarter 2 of 2021 to support the second half growth.

對於第 2 季度，我們預計銷售額將增長中個位數，受益於上一年前向採購逆轉增加約 3 個百分點。對於核心營業收入，我們預計 2021 年上半年的核心營業收入將下降低個位數，原因是上一年成本基數較低，以及 2021 年第二季度的投資以支持下半年的增長。

In summary, quarter 1 showed a solid underlying performance for Innovative Medicines, challenging for Sandoz, but allowed us to reconfirm our full year guidance. In quarter 2, we expect to benefit from the reversal of forward purchasing and some improved momentum in the U.S. given the speed of vaccinations in that key market. Our current and expected performance also allows us to reiterate our confidence that we will grow top and bottom line every year to 2025 and meet external expectations.

總而言之，第一季度創新藥物表現出穩健的基本表現，對山德士來說具有挑戰性，但讓我們能夠重新確認我們的全年指導。在第二季度，鑑於該關鍵市場的疫苗接種速度，我們預計將受益於遠期採購的逆轉和美國的一些改善勢頭。我們當前和預期的表現也使我們能夠重申我們的信心，即到 2025 年，我們將每年增加收入和利潤，並滿足外部預期。

And with that, I hand it back to Vas.

有了這個，我把它交還給 Vas。

Perfect. Thank you, Harry. I wanted to highlight before closing that we do have a catalyst-rich period coming up for the remainder of this year. A number of submissions, as you see here on the chart, a number of important readouts that would enable submissions either this year or next year. So we'll look forward to keeping you up-to-date on these readouts as they happen over the course of this year and also present the data at major congresses.

完美的。謝謝你，哈利。在結束之前，我想強調一下，今年剩下的時間裡，我們確實會有一個催化劑豐富的時期。正如您在圖表上看到的，許多提交的內容，一些重要的讀數將使今年或明年的提交成為可能。因此，我們期待在今年的過程中讓您了解這些讀數的最新信息，並在主要會議上展示這些數據。

So moving to the next slide and in closing, I think you've heard now from all of us that we have confidence in our growth drivers and launches to continue their strong momentum. You've seen that underlying performance starting to come through and momentum is picking up. Solid IM top and bottom line performance. And even when you take into account the prior year purchasing, you really see underlying the performance come through. Our broad pipeline of novel medicines in Phase II and Phase III continue to progress well. And we're confident in delivering our 2021 and more importantly, our longer-term top and bottom line growth outlook.

因此，轉到下一張幻燈片並結束，我想你們現在已經從我們所有人那裡聽到，我們對我們的增長動力和發布充滿信心，以繼續保持強勁勢頭。您已經看到潛在的表現開始顯現並且勢頭正在回升。穩定的 IM 頂線和底線性能。即使考慮到上一年的購買情況，您也確實看到了潛在的表現。我們在 II 期和 III 期的廣泛的新藥管道繼續取得良好進展。我們有信心實現我們的 2021 年，更重要的是，我們的長期頂線和底線增長前景。

So with that, operator, we can open the line for questions. (Operator Instructions) Operator?

因此，接線員，我們可以打開問題線。 （操作員說明）操作員？

(Operator Instructions) Your first question today comes from the line of Mark Purcell from Morgan Stanley.

（操作員說明）您今天的第一個問題來自摩根士丹利的 Mark Purcell。

So one on cardiovascular outcome studies, one on Kesimpta, please. In terms of the ORION-4 study, I just wondered if there's anything more you can say about the delay from December '24 to 2026. And whether, given you're still recruiting patients, this study I think is run by Oxford University, whether there's the option to add more patients to try and expedite the readout. The reason why I ask is that there's been a recent update for TQJ230, and the HORIZON study is still on track to complete in March 2024. So I'm not sure what's unusual or otherwise about ORION-4.

所以請一份關於心血管結果研究，一份關於 Kesimpta。關於 ORION-4 研究，我只是想知道您是否可以對從 12 月 24 日到 2026 年的延遲說更多的話。鑑於您仍在招募患者，我認為這項研究是否由牛津大學開展，是否可以選擇添加更多患者以嘗試加快讀數。我問的原因是 TQJ230 最近有更新，而 HORIZON 研究仍有望在 2024 年 3 月完成。所以我不確定 ORION-4 有什麼不尋常或其他方面。

And then secondly, on Kesimpta, Marie-France, one for you. Could you help us understand the latest NBRx share trends in the United States? And as the sort of patient flow comes back and your promotion responds in kind, where you feel the NBRx share should evolve during the course of this year.

其次，在 Kesimpta，Marie-France，為您準備了一份。您能幫助我們了解美國最新的 NBRx 股票趨勢嗎？隨著患者流量的恢復和您的促銷以實物形式回應，您認為 NBRx 份額應該在今年內發展。

Great. Thanks, Mark. So John, you want to take the CV outcome study?

偉大的。謝謝，馬克。那麼約翰，你想參加簡歷結果研究嗎？

Sure. Will do. Thanks, Mark. Thanks for the question on Leqvio. As we noted in Meet Novartis Management last year at the end of the year that our expectations for Leqvio at that time was conclusion in 2025. We've seen a pretty significant impact. As you know, we're doing the study with the Oxford group, where the majority of our patients are recruited from the U.K. And as we've seen, both with COVID and then the additional variance with the impact of COVID in the U.K., recruitment has been challenging. Initially in December, as we saw, there was an uptick in COVID cases in the U.K. And then subsequently, throughout the first quarter of the year in the U.K., there was significant impact of COVID.

當然。會做。謝謝，馬克。感謝關於 Leqvio 的問題。正如我們去年年底在與諾華管理層會面中指出的那樣，我們當時對 Leqvio 的預期是在 2025 年結束。我們已經看到了相當大的影響。如您所知，我們正在與牛津小組進行研究，我們的大多數患者都是從英國招募的，正如我們所見，無論是 COVID 還是 COVID 在英國的影響的額外差異，招聘一直充滿挑戰。正如我們所見，最初在 12 月，英國的 COVID 病例有所上升。隨後，在英國的整個第一季度，COVID 產生了重大影響。

So based on the recruitment time lines, we actually have deferred the study results to 2026 because during that time, I think the health care systems were overwhelmed with taking care of COVID patients. So it was very difficult to recruit these patients. As we've had discussions with the Oxford group, I think recruitment is starting to tick back on track, and we're working very closely in terms of report out of the results in 2026.

因此，根據招募時間線，我們實際上已將研究結果推遲到 2026 年，因為在那段時間裡，我認為醫療保健系統不堪重負照顧 COVID 患者。因此，招募這些患者非常困難。隨著我們與牛津集團的討論，我認為招聘開始回到正軌，我們正在密切合作，以報告 2026 年的結果。

Yes. Thanks, John. And just one additional note. Across other studies like TQJ230, where we had a global footprint, we've been able to flex our recruitment around the world to maintain time lines. In this particular study, given the high proportion of patients from the U.K. NHS, there just was a bigger impact. We, of course, look at all ways to expedite the study in the meantime.

是的。謝謝，約翰。只有一個附加說明。在我們擁有全球足蹟的 TQJ230 等其他研究中，我們已經能夠在全球範圍內靈活招聘以保持時間線。在這項特殊的研究中，鑑於英國 NHS 的患者比例很高，因此產生了更大的影響。當然，在此期間，我們會考慮各種加快研究的方法。

On Kesimpta, Marie-France?

在 Kesimpta，Marie-France？

Yes. So thanks for the question. The first thing to note is that our U.S. launch is progressing really well. And as I said in my opening remarks, the areas that are under our control are progressing really well. We talked about positioning. We talked about the first-line first switch at 50%; ease of initiation, which was very important for us; and access where we already have 75% of commercial lives covered. So based on that, we saw that paid product is growing faster than expected. And we're also looking at 65% of sales in the second half of the year. Previously, we had said 75%.

是的。所以謝謝你的問題。首先要注意的是，我們在美國的發射進展非常順利。正如我在開場白中所說，我們控制的領域進展非常順利。我們談到了定位。我們講了50%的一線先切換；易於啟動，這對我們來說非常重要；並進入我們已經覆蓋了 75% 的商業生活的地方。因此，基於此，我們看到付費產品的增長速度快於預期。我們還預計下半年的銷售額將達到 65%。以前，我們說的是 75%。

If I pivot to the NBRx, we're currently at 10%. But as you know, the dynamic market's still suppressed. And we see hesitation to switch patients or to initiate patients on B-cell therapies prior to vaccinations. As the market bounces back, and as we see vaccination campaigns progress, I believe that we'll see a significant uplift in the NBRxs for Kesimpta.

如果我轉向 NBRx，我們目前為 10%。但如你所知，充滿活力的市場仍然受到壓制。我們看到在接種疫苗之前猶豫是否更換患者或讓患者接受 B 細胞療法。隨著市場反彈，以及我們看到疫苗接種活動取得進展，我相信我們將看到 Kesimpta 的 NBRxs 顯著提升。

We're also bringing additional markets -- or Kesimpta to additional markets, and we can also expect strong uptake based on the efficacy. As we said, we talk about 1 relapse every 9 to 10 patient years. And now, we've got additional evidence that shows that Kesimpta reduces risk of progression independent of relapses by up to 60% in naive patients. So all of this points to a tremendous opportunity for patients and for this product.

我們還為其他市場帶來了更多的市場——或 Kesimpta，我們還可以期待基於療效的強勁吸收。正如我們所說，我們談論每 9 到 10 個患者年 1 次復發。現在，我們有更多的證據表明 Kesimpta 可將與復發無關的進展風險降低高達 60% 的幼稚患者。因此，所有這些都為患者和該產品提供了巨大的機會。

We're also very confident that we'll see a big expansion in the B-cell market. So currently, we see around 30% in the U.S., and we expect that number to get to 50% over the next couple of years.

我們也非常有信心看到 B 細胞市場的大幅擴張。所以目前，我們在美國看到大約 30%，我們預計這個數字將在未來幾年達到 50%。

Thanks, Marie-France.

謝謝，瑪麗-法蘭西。

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

您的下一個問題來自美國銀行的 Graham Parry。

So another one on Kesimpta actually and the free versus paid for Rx. I think you previously said it was around 30% paid for and you're aiming to get that to 70% by the end of the year. So if you could just give us an update on where you are now and where you expect that to be at the end of the year that drives the 65% number?

所以實際上是 Kesimpta 上的另一個，免費與付費的 Rx。我想你之前說過大約是 30% 的費用，而你的目標是到今年年底達到 70%。因此，如果您可以向我們提供有關您現在的最新情況以及您預計在今年年底將達到的位置，從而推動 65% 的數字？

And then secondly, on Sandoz, just -- you talked about stabilization in the second half of the year. But if margins are down largely because of price, is there a risk that this just doesn't reverse thereafter? So perhaps help us to understand what happens into 2022. And where are you in terms of the separation of Sandoz into a fully autonomous unit inside Novartis? I think you'd said it was probably around middle of this year that would be complete. And is that the point at which you then decide whether Novartis remains the best owner of Sandoz?

其次，關於 Sandoz，您剛剛談到了下半年的穩定。但是，如果利潤率下降主要是因為價格，那麼這種情況是否存在此後不會逆轉的風險？因此，也許可以幫助我們了解 2022 年會發生什麼。在將 Sandoz 分離成諾華內部的一個完全自主的單元方面，你在哪裡？我想你說過這可能會在今年年中左右完成。那是你決定諾華是否仍然是山德士最好的所有者的時候嗎？

Thanks, Graham. On -- first, on Kesimpta, back to you Marie-France.

謝謝，格雷厄姆。關於——首先，在 Kesimpta，回到你 Marie-France。

Yes. So currently, we have about 2,400 patients treated on Kesimpta. And as you pointed out, we have a 12-month bridging program. When we discussed this at the end of Q4, we were actually looking at 30% paid with 70% free. That has radically changed. So it looks like we flipped those numbers, and we're currently at 70% paid product. We expect that to get up to 80% for the rest of the year, and that's why we've changed our percentage sales for the second half of the year from 75% to 65%.

是的。所以目前，我們有大約 2,400 名患者接受 Kesimpta 治療。正如你所指出的，我們有一個為期 12 個月的過渡計劃。當我們在第四季度末討論這個問題時，我們實際上是在考慮 30% 的付費和 70% 的免費。這已經發生了根本性的變化。所以看起來我們顛倒了這些數字，我們目前有 70% 的付費產品。我們預計今年剩餘時間這一比例將達到 80%，這就是我們將下半年的銷售額百分比從 75% 更改為 65% 的原因。

Great. And then on Sandoz stabilization and dynamics, Richard?

偉大的。然後是 Sandoz 的穩定性和動態性，Richard？

Thank you, Graham. We've already assumed the level of price erosion going through the rest of the year. You got to remember, a lot of that's been driven because of volume declines we saw in Q1. And with volume declines, you saw a stabilization in the market, service levels go up. And invariably, that means that the competition for price goes up as well.

謝謝你，格雷厄姆。我們已經假設了今年剩餘時間的價格侵蝕水平。您必須記住，其中很大一部分是由於我們在第一季度看到的銷量下降所致。隨著銷量下降，您看到市場趨於穩定，服務水平上升。這總是意味著價格競爭也會加劇。

We assume that will start to wash through and wash out as we go to the second half. We also assume there will be a normalization in demand, patients start returning back to hospital, elective surgery. And we also anticipate a slightly stronger cough and cold season, given it really had very little this season with social distancing. So there's a number of drivers, and we've already assumed the level of price erosion going on through the rest of the year.

我們假設隨著我們進入下半場，這將開始洗刷和洗刷。我們還假設需求將正常化，患者開始返回醫院，進行擇期手術。而且我們還預計咳嗽和感冒的季節會稍微強一些，因為這個季節實際上很少有社交距離。因此，有許多驅動因素，我們已經假設了今年剩餘時間的價格侵蝕程度。

And I'll let Vas comment on the Sandoz in autonomy.

我會讓 Vas 在自治方面評論 Sandoz。

Yes. Thanks, Richard. So -- and thanks, Graham. On Sandoz, we've now successfully separated the manufacturing unit with links to our global manufacturing. And I think in most of the relevant areas, Sandoz is now enabled to compete at the relevant cost structure and flexibility to be successful as the leading generics player.

是的。謝謝，理查德。所以——謝謝，格雷厄姆。在山德士，我們現在已經成功地將製造單元與我們的全球製造聯繫起來。我認為在大多數相關領域，山德士現在能夠以相關成本結構和靈活性競爭，成為領先的仿製藥廠商。

Our focus now is to get Sandoz, as we've stated consistently, to a consistent mid-single-digit sales growth and core operating margins that are in line with the top end of the peer set, which would be in the high 20s. And that's where our energy and focus is. A lot of that is getting to world-class launches and biosimilars, getting our oral solids business and launches back on track in the U.S. as well as being at market formation for key launches in Europe. And that's what we're really focused on at the moment. Thanks, Graham.

正如我們一直所說的那樣，我們現在的重點是讓山德士保持一致的中個位數銷售增長和核心營業利潤率，與同行的最高端一致，這將是 20 多歲的高點。這就是我們的精力和重點所在。其中很大一部分是用於世界級的發布和生物仿製藥，使我們的口服固體業務和在美國的發布重回正軌，以及在歐洲的主要發布中處於市場形成階段。這就是我們目前真正關注的內容。謝謝，格雷厄姆。

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

下一個問題來自花旗的 Andrew Baum。

A couple of questions, please. With inclisiran, you attained a pre-approval agreement with the U.K. I'm wondering whether you have or will be entering into similar agreements with European territories for your PD-1 license from BeiGene? That's the first question.

有幾個問題，請。通過 inclisiran，您與英國達成了預先批准協議。我想知道您是否已經或將要與歐洲地區就百濟神州的 PD-1 許可達成類似協議？這是第一個問題。

Second question is, could you talk to which subpopulations, VA, [internal medicine] health, within the U.S. where you may be able to get entry with tislelizumab.

第二個問題是，您能否談談在美國哪些亞群、VA、[內科]健康方面您可以使用 tislelizumab。

And then finally, if you have a second to comment on how you look at the competitive outlook for Lucentis given we've been surprised by ophthalmologists feedback on faricimab ahead of anticipated approval.

最後，如果您有時間評論一下您如何看待 Lucentis 的競爭前景，因為我們對眼科醫生在預期批准之前對 faricimab 的反饋感到驚訝。

Great. Thanks, Andrew. So both PD-1 questions in Europe and U.S., Susanne?

偉大的。謝謝，安德魯。那麼歐洲和美國的 PD-1 問題，Susanne？

Yes, sure. Andrew. So our ambition is to provide global access to tislelizumab is in the broad array of indications. As you know, BeiGene is running a very broad development program, and that is really our first ambition. We really want to establish tislelizumab in key indications where PD-1s are currently marked and also pursue novel combinations with our portfolio. So really short term, the focus is on getting first indications filed. We plan to file in non-small cell lung cell cancer and esophageal cancer. And we expect these to be submitted in the second half of 2021.

是的，當然。安德魯。因此，我們的目標是在廣泛的適應症中提供對 tislelizumab 的全球訪問。如您所知，百濟神州正在開展一個非常廣泛的發展計劃，這確實是我們的第一個目標。我們真的希望在目前標記 PD-1 的關鍵適應症中建立 tislelizumab，並尋求與我們的產品組合的新組合。所以真的很短期，重點是獲得第一個跡象。我們計劃申報非小細胞肺癌和食道癌。我們預計這些將在 2021 年下半年提交。

On specific agreements, I don't want to comment. You have seen the data. We have very solid OS data presented at AACR. And we believe that tislelizumab is a very differentiated PD-1.

關於具體協議，我不想發表評論。你已經看到數據了。我們在 AACR 上展示了非常可靠的操作系統數據。而且我們認為，tislelizumab 是一種非常差異化的 PD-1。

So in terms of subpopulations, we, of course, want to make sure that we focus on the areas where tislelizumab is differentiated. And I think the 2 data readouts show that I think there is still space for a strong PD-1. So that's for now, and then we work through reimbursement agreements while we then prepare for launch.

因此，就亞群而言，我們當然希望確保我們專注於 tislelizumab 的差異化領域。而且我認為 2 個數據讀數表明我認為強大的 PD-1 仍有空間。所以這就是現在，然後我們通過報銷協議工作，然後我們準備發布。

Thanks, Susanne. And then on Lucentis, Marie-France?

謝謝，蘇珊。然後在Lucentis，Marie-France？

Yes. So Lucentis did really well in Q1. It's growing 4% due to the steady performance in Europe. So there is some rebound. We can expect to see that to continue and also the strong NRDL-driven momentum in China, which is definitely where we're looking to see a good chunk of our growth this year. So for the remainder of the year, we expect to see Lucentis grow at low single digits and again, with China being a major driver.

是的。所以 Lucentis 在第一季度的表現非常好。由於歐洲的穩定表現，它增長了 4%。所以有一些反彈。我們可以期待看到這種情況繼續下去，以及中國國家醫保目錄驅動的強勁勢頭，這絕對是我們今年希望看到很大一部分增長的地方。因此，在今年餘下的時間裡，我們預計 Lucentis 將再次以低個位數增長，中國將成為主要驅動力。

In terms of the competition, just remind you that Lucentis is really established in the market, and we believe we'll continue to do well. One of the key drivers is just a very complete indication portfolio that Lucentis has and that newer products will not bring to market immediately.

在競爭方面，提醒您，Lucentis 確實在市場上站穩腳跟，我們相信我們會繼續做得很好。關鍵驅動因素之一是 Lucentis 擁有非常完整的適應症產品組合，並且新產品不會立即推向市場。

Thanks, Marie-France. Thank you, Andrew.

謝謝，瑪麗-法蘭西。謝謝你，安德魯。

Your next question comes from the line -- I'm sorry. Your next question comes from the line of Keyur Parekh from Goldman Sachs.

你的下一個問題來自這條線——對不起。您的下一個問題來自高盛的 Keyur Parekh。

Two, please. One, Vas, I know you kind of suggested that the Sandoz separation is kind of -- or the independent company is kind of on group. But can you just remind us conceptually the positive, the negatives from a Novartis perspective of keeping Sandoz in-house. Kind of it's been a drag on your growth as long as one can remember. So just conceptually, why does it belong within the Novartis equity story would be great.

兩個，請。一，Vas，我知道你暗示 Sandoz 的分離有點——或者獨立公司有點像集團。但是，您能否在概念上提醒我們，從諾華（Novartis）的角度來看，將山德士保留在內部是積極的、消極的。只要人們記得，它就一直在拖累你的成長。所以從概念上講，為什麼它屬於諾華股票故事會很棒。

And then separately, for Marie-France on Zolgensma. As we think about kind of the next few quarters, can you just remind us of the incremental countries you're going to be launching the product in and the size of the bolus opportunity in those countries?

然後分別為 Zolgensma 上的 Marie-France。當我們考慮接下來的幾個季度時，您能否提醒我們您將在哪些國家/地區推出該產品以及這些國家/地區的推注機會的規模？

Yes. Thanks, Keyur. So on Sandoz, there's I think a few considerations. One, historically, and we continue to believe, in certain markets, there is commercial synergies in having a broad portfolio across generics and Innovative Medicines. We, of course, continue to challenge ourselves and evaluate that, but we do have those agreements in certain markets. And that depending on how health care systems evolve in the future, it could be an advantage to have one of the largest, if not the largest by volume generics company in the world.

是的。謝謝，凱爾。所以在 Sandoz 上，我認為有一些考慮因素。一，從歷史上看，我們繼續相信，在某些市場上，在仿製藥和創新藥物之間擁有廣泛的產品組合具有商業協同效應。當然，我們會繼續挑戰自己並對此進行評估，但我們確實在某些市場上達成了這些協議。這取決於未來醫療保健系統的發展方式，擁有世界上規模最大的仿製藥公司之一可能是一種優勢，如果不是最大的仿製藥公司的話。

The other part of the story, of course, is biosimilars, where our manufacturing scale and know-how enables us -- as well as our development expertise, enables us to enable Sandoz to build a leading biosimilars portfolio. And then, of course, the company will benefit over time. And we're hopeful that the Sandoz biosimilars portfolio can help us get Sandoz to that mid-single-digit growth, up on the margin spectrum and then contribute to the growth of the overall company.

當然，故事的另一部分是生物仿製藥，我們的製造規模和專業知識使我們能夠——以及我們的開發專業知識，使山德士能夠建立領先的生物仿製藥產品組合。然後，當然，公司將隨著時間的推移而受益。我們希望 Sandoz 生物仿製藥產品組合能夠幫助我們讓 Sandoz 實現中個位數的增長，提高利潤率，然後為整個公司的增長做出貢獻。

Those, I think, are the 2 key considerations. There is, of course, the broader software consideration that Sandoz serves hundreds of millions of patients and provides billions of doses to humanity, which is consistent with the overall purpose of the company to reimagine medicine. So on Zolgensma, Marie-France?

我認為，這是兩個關鍵的考慮因素。當然，還有更廣泛的軟件考慮，山德士為數億患者服務並為人類提供數十億劑，這與公司重新構想醫學的總體目標是一致的。那麼關於 Zolgensma，Marie-France？

Yes. So in the U.S., our business is driven by the incident patients. So the growth ex U.S. is coming from these recent reimbursement wins in Europe. For the rest of 2021, we expect the U.S. business to remain stable and to be -- continue to be driven by the incident patients.

是的。所以在美國，我們的業務是由事件患者驅動的。因此，美國以外的增長來自歐洲最近的這些報銷勝利。在 2021 年剩下的時間裡，我們預計美國業務將保持穩定，並將繼續受到事件患者的推動。

In Europe, we're working on securing reimbursement in additional countries. Right now, we've seen good uptake in Germany and recent reimbursement and acceleration in smaller markets, such as Czech Republic or UAE. If we look at the nature of the European markets, we also expect to see reimbursement on a rolling basis.

在歐洲，我們正在努力確保在其他國家/地區獲得報銷。目前，我們已經看到德國的良好吸收以及最近在捷克共和國或阿聯酋等較小市場的報銷和加速。如果我們看看歐洲市場的性質，我們還希望看到滾動報銷。

What you can expect going forward is the U.K. and Italy, where we've now secured reimbursement, and that will bring Zolgensma to additional patients. As we've said before, the initial source of business in all of the launches comes from previously treated patients. And over time, that patient mix shifts to the incident population. Overall, for 2021, we expect blockbuster status with Zolgensma.

你可以期待的是英國和意大利，我們現在已經獲得了報銷，這將把 Zolgensma 帶到更多的患者身上。正如我們之前所說，所有發布的最初業務來源都來自之前接受過治療的患者。隨著時間的推移，這種患者組合會轉移到事件人群中。總體而言，對於 2021 年，我們預計 Zolgensma 將成為重磅炸彈。

Thanks, Marie-France. Thanks, Keyur.

謝謝，瑪麗-法蘭西。謝謝，凱爾。

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。

Emmanuel Papadakis from Deutsche Bank. Maybe a couple of products, specific ones. Just on iptacopan, the Phase 2, we're going to see the IgAN relatively soon, obviously, perhaps you could give us any commentary around the conference.

德意志銀行的 Emmanuel Papadakis。也許是幾個產品，具體的。就在 iptacopan，第 2 階段，我們將很快看到 IgAN，顯然，也許您可以就會議給我們任何評論。

And just -- I mean, in terms of data itself, have you hit primary -- if I recall, the end point was UPCR. Should we expect to see a consistent benefit on the key secondaries like eGFR? And what would you regard as a clinically meaningful improvement on the primary and any key secondaries?

只是 - 我的意思是，就數據本身而言，你是否達到了初級 - 如果我記得，終點是 UPCR。我們是否應該期望看到像 eGFR 這樣的關鍵二級數據持續受益？您認為對原發性和任何關鍵繼發性有臨床意義的改進是什麼？

And then maybe a question on the shift to TNO155. Just your take on any ramifications from some competition data we saw at AACR. Can you just remind us your confidence on that program's potential and when we should be looking to see the first KRAS combination data? Or if you no longer believe that is the most promising combination, what we should be particularly anticipating in terms of the various combination studies you have ongoing with that molecule.

然後可能是關於轉向 TNO155 的問題。只是您對我們在 AACR 上看到的一些競爭數據的任何影響的看法。您能否提醒我們您對該計劃潛力的信心，以及我們何時應該看到第一個 KRAS 組合數據？或者，如果您不再認為這是最有希望的組合，那麼我們應該特別期待您對該分子正在進行的各種組合研究。

Thanks, Emmanuel. So John, you want to start on IgA nephropathy.

謝謝，伊曼紐爾。所以約翰，你想從 IgA 腎病開始。

Sure. Thanks for the question, Emmanuel. As you know, for iptacopan, we're looking across a number of indications, including IgA nephropathy, also C3 glomerulopathy as well as PNH. Specifically in IgA nephropathy, we do have the Phase II dose range finding study, which is ongoing. We've had an interim readout, and based on that interim readout, we've already decided to advance into the Phase III studies. Those results will be coming out before the half of the year. The specific conference, we -- the posters and abstracts have not been released. So we've refrained from telling you exactly, but we are confident that those results will be presented before the first half of the year.

當然。謝謝你的問題，伊曼紐爾。如您所知，對於 iptacopan，我們正在研究多種適應症，包括 IgA 腎病、C3 腎小球病以及 PNH。特別是在 IgA 腎病方面，我們確實進行了 II 期劑量範圍研究，該研究正在進行中。我們有一個臨時讀數，基於該臨時讀數，我們已經決定進入 III 期研究。這些結果將在今年上半年之前公佈。具體的會議，我們——海報和摘要還沒有發布。所以我們沒有確切地告訴你，但我們相信這些結果將在今年上半年之前公佈。

And as I said, the Phase III has advanced as we move forward in IgA nephropathy and the expected filing is based on conditional approval for proteinuria reduction at 9 months. So these are the same results in the Phase II, which we have in the Phase III study. And as you asked about the secondary end point, these are the same secondary endpoints that we have in our Phase III study. The final approval, which is expected to be in 2025, is based on the eGFR slope. And this was the Phase II study that we had in place and also is the end point also for a full approval expectation in 2025 based on results.

正如我所說，隨著我們在 IgA 腎病方面的進展，第三階段已經推進，預期的備案是基於在 9 個月時有條件地批准減少蛋白尿。所以這些與我們在第三階段研究中的第二階段結果相同。正如您所問的次要終點，這些與我們在 III 期研究中的次要終點相同。最終批准預計在 2025 年進行，基於 eGFR 斜率。這是我們進行的第二階段研究，也是基於結果的 2025 年全面批准預期的終點。

So I think the second question that you had was around the SHP2 inhibitor, and how should we be thinking about the SHP2 inhibitor as we move forward. As you know, SHP2 is as tyrosine phosphatase and acts at a really important node as we look at the RAS/MAP kinase pathway. And in preclinical studies, what we saw was not only single-agent activity, but also in combination with other agents.

所以我認為你提出的第二個問題是關於 SHP2 抑製劑，以及在我們前進的過程中我們應該如何考慮 SHP2 抑製劑。如您所知，SHP2 就像酪氨酸磷酸酶一樣，在我們研究 RAS/MAP 激酶通路時作用於一個非常重要的節點。在臨床前研究中，我們看到的不僅是單藥活性，還包括與其他藥物聯合使用。

Our strategy for our SHP2 inhibitor is that we expect to go broadly in terms of a number of combinations. And as we look at the approach that we're taking, there's 4 potential areas that we're currently looking at. First is in combination with our own eGFR agent. This would be our third-generation EGRF agent -- eGFR agent, and this would be our first consideration for combination with our SHP2 inhibitor. Secondly is looking at the role of SHP2 in immune cells. And so that consideration would be with PD-1, and we have a study ongoing with spartalizumab.

我們對 SHP2 抑製劑的策略是，我們希望廣泛地採用多種組合。當我們審視我們正在採取的方法時，我們目前正在研究 4 個潛在領域。首先是與我們自己的 eGFR 代理相結合。這將是我們的第三代 EGRF 劑——eGFR 劑，這將是我們與 SHP2 抑製劑聯合使用的首要考慮因素。其次是研究 SHP2 在免疫細胞中的作用。因此，考慮將與 PD-1 相關，我們正在進行一項與斯巴達珠單抗相關的研究。

Thirdly, would be looking at the MAP kinase/RAS pathway as we look at the combination with potentially KRAS G12C. And also, we have a study in place with Kisqali. And then fourth would be -- we currently have an early study in combination with dabrafenib, trametinib as we look at the treatment for BRAF V600 mutant CRC patients. So we have high expectations in combination with our SHP2 inhibitor looking broadly, in addition to the KRAS G12C pathway.

第三，當我們研究與潛在的 KRAS G12C 的組合時，將研究 MAP 激酶/RAS 途徑。而且，我們與 Kisqali 進行了一項研究。然後第四個是——我們目前有一項與 dabrafenib、trametinib 聯合的早期研究，因為我們正在研究 BRAF V600 突變 CRC 患者的治療方法。因此，除了 KRAS G12C 通路外，我們對 SHP2 抑製劑的廣泛應用抱有很高的期望。

Thanks, John. And maybe just to highlight again, we're not focused here on single agent. I couldn't hear your question, Emmanuel. We really think the opportunity for SHP2 will be in combination and hopefully, in combination with a range of agents. And that data should come out over the coming 18 months.

謝謝，約翰。也許只是為了再次強調，我們在這裡並不專注於單一代理。我聽不見你的問題，伊曼紐爾。我們真的認為 SHP2 的機會將結合併希望與一系列代理結合。這些數據應該會在未來 18 個月內公佈。

Your next question comes from the line of Matthew Weston from Credit Suisse.

您的下一個問題來自瑞士信貸的 Matthew Weston。

Two questions, please. The first on U.S. tax reform. So Novartis, like many in the pharma industry, is a major beneficiary of transfer pricing. I'd be very interested in Harry's view of the long-term tax rate given the discussions that are being had or proposed by President Biden about changing the way multinational tax is calculated with minimum revenue-based metrics on a national approach. And I -- also in the shorter term, if you could just give us some update as to the likely nearer-term impact of anything we've learned from the near-term U.S. domestic Biden tax changes. That would be extremely interesting.

請教兩個問題。第一個是關於美國稅制改革的。因此，與製藥行業的許多人一樣，諾華是轉讓定價的主要受益者。鑑於拜登總統正在討論或提出的關於改變跨國稅收計算方式的討論，我會對哈里對長期稅率的看法非常感興趣，並在全國范圍內使用基於最低收入的指標。我 - 也是在短期內，如果你能給我們一些關於我們從近期美國國內拜登稅收變化中學到的任何東西可能產生的近期影響的最新信息。那將是非常有趣的。

And then secondly, a product-specific question regarding the DARPin collaboration in COVID. Can you just give us an update on the project, both in terms of the early clinical data that we've seen on the first DARPin, how the tech transfer is progressing to Sandoz and your thinking as to when we might have something to file from that program?

其次，關於 COVID 中 DARPin 合作的產品特定問題。您能否向我們介紹一下該項目的最新情況，包括我們在第一個 DARPin 上看到的早期臨床數據、技術轉移到 Sandoz 的進展情況以及您對我們何時可以提交文件的想法那個程序？

Yes. Thanks, Matthew. So first on tax reform, Harry?

是的。謝謝，馬修。那麼首先是稅收改革，哈利？

So as you know, this year, we guide to about 16% core tax rate. Last year, it was 15.4%. We saw -- see in the midterm the 16% to 17%, given the current tax laws. Now of course, the Biden proposal, the U.S. part would not be a positive for anybody, if you will, right, from a tax rate standpoint. But our exposure to the U.S., if you will, is relatively low given that the majority of our IP and a lot of substance is in Switzerland.

如您所知，今年我們將核心稅率引導至 16% 左右。去年，這一比例為 15.4%。鑑於當前的稅法，我們看到 - 在中期看到 16% 到 17%。當然，拜登的提議，如果你願意的話，從稅率的角度來看，美國部分對任何人都不是積極的。但是，如果您願意的話，我們在美國的曝光率相對較低，因為我們的大部分知識產權和大量內容都在瑞士。

And the other issue with all of this is, of course, that not many details are available. And therefore, I don't want to go into any speculations because we don't know if and what will be and implemented. We don't see anything changing for this year or any time soon. And the moment we have details, of course, we would come up with the respective scenarios.

當然，所有這一切的另一個問題是沒有多少細節可用。因此，我不想進行任何猜測，因為我們不知道是否以及將會實施什麼。我們認為今年或近期內沒有任何變化。當然，一旦我們有了細節，我們就會想出各自的場景。

Great. Thanks, Harry. And then on the Molecular Partners collaboration, just to remind the group, the idea here was to pursue the DARPin technology, which is a naturally occurring technology -- a naturally occurring protein-based molecule that acts in a completely different way to monoclonal antibody, but with a similar effect. The first DARPin -- set of DARPins for COVID showed very strong preclinical efficacy in preclinical models, also against the variant at the Molecular Partners-Novartis collaboration.

偉大的。謝謝，哈利。然後在 Molecular Partners 的合作中，提醒小組，這裡的想法是追求 DARPin 技術，這是一種天然存在的技術——一種天然存在的基於蛋白質的分子，其作用方式與單克隆抗體完全不同，但具有類似的效果。第一個 DARPin——一組用於 COVID 的 DARPin 在臨床前模型中顯示出非常強的臨床前療效，也針對 Molecular Partners-Novartis 合作的變體。

We've completed the Phase I study, which will enable a Phase II/III start shortly. We target a readout in the Q3 time frame, which we expect to enable an emergency use authorization, the -- if positive. The benefits of this approach would be: one, the potential for a subcu injection versus IV; and two, because this technology can be produced in bacterial fermentation -- or use fermentation, I should say, much lower COGS for the medicine, which would enable hopefully, broad-scale use. Also much higher volumes could be produced versus mammalian cell monoclonal antibodies. So a lot to still work through and figure out, but we're working through it now and hopefully, with the study start and then the ultimate readout over the course of the summer. Thank you, Matthew.

我們已經完成了 I 期研究，這將使 II/III 期很快開始。我們的目標是在第三季度的時間範圍內進行讀數，我們希望能夠啟用緊急使用授權，如果是肯定的。這種方法的好處是：一，subcu 注射與 IV 相比的潛力；第二，因為這項技術可以在細菌發酵中生產——或者使用發酵，我應該說，藥物的 COGS 低得多，這有望實現大規模使用。與哺乳動物細胞單克隆抗體相比，還可以產生更高的體積。所以還有很多工作要做，但我們現在正在努力，希望隨著研究的開始，然後是整個夏天的最終結果。謝謝你，馬修。

Next question comes from the line of Richard Parkes from Exane BNP.

下一個問題來自 Exane BNP 的 Richard Parkes。

Firstly, on Zolgensma, just in the U.S., I just wondered if you could talk a little bit more about where you are in terms of penetration of the incident SMA patient population. It looks like it's just 60%, but I wondered what room there was for that to move higher based on screening improvements. And maybe you could discuss that and where you are in terms of share amongst the various treatment options in that population, whether that's been impacted by the Evrysdi launch. Also, I remember you talking about seeing physicians delaying starts due to COVID. I'm just wondering whether that's no longer the case.

首先，關於 Zolgensma，就在美國，我只是想知道您是否可以多談談您在 SMA 患者人群中的滲透率。看起來只有 60%，但我想知道基於篩選改進還有什麼空間可以提高。也許您可以討論這一點以及您在該人群中各種治療方案中的份額，無論這是否受到 Evrysdi 推出的影響。另外，我記得您談到看到醫生因 COVID 而推遲開始。我只是想知道是否不再是這種情況。

Then second question is we've heard from some other management teams that seem to be expressing some optimism that a compromised solution on U.S. drug pricing could be achievable given the current balance of power in the Senate? And I just wondered what Novartis' perspective on that was and your thoughts on what might happen medium term.

然後第二個問題是，我們從其他一些管理團隊那裡聽到，他們似乎表示樂觀地認為，鑑於參議院目前的權力平衡，可以實現對美國藥品定價的妥協解決方案？我只是想知道諾華對此的看法是什麼，以及你對中期可能發生的事情的看法。

Yes. Thanks, Richard. So I'll just quickly take the Zolgensma U.S. question. For Zolgensma right now, the principal driver of business is the newborn screening programs around the country, which in those screening programs, a very high -- nearly all patients tend to get Zolgensma. Right now, newborn screening is covering about 70% of newborn lives. We hope to get that number up to 82% before the end of the year. And that would be then the steady-state driver for Zolgensma. And then we continue to see some utilization in switch patients who are in the so-called prevalent pool or on an alternative therapy and then switch to Zolgensma.

是的。謝謝，理查德。所以我會很快回答 Zolgensma 美國的問題。對於 Zolgensma 來說，目前業務的主要驅動力是全國各地的新生兒篩查項目，在這些篩查項目中，這一比例非常高——幾乎所有患者都傾向於得到 Zolgensma。目前，新生兒篩查覆蓋了大約 70% 的新生兒生命。我們希望在今年年底前將這一數字提高到 82%。這將是 Zolgensma 的穩態驅動因素。然後我們繼續看到在所謂的流行池或替代療法中的轉換患者中的一些使用，然後轉換到 Zolgensma。

So we do believe we're at a steady state in the U.S. with some potential growth as newborn screening continues to expand over the coming years. And that's kind of how we think about the U.S. Zolgensma opportunity.

因此，我們相信隨著新生兒篩查在未來幾年繼續擴大，我們在美國處於穩定狀態，並有一些潛在的增長。這就是我們對美國 Zolgensma 機會的看法。

As we stated in the presentation, we continue to work through the nonhuman primate studies to enable AVXS-101 intrathecal to be lifted off of clinical hold, and then we would rapidly want to advance that program through Phase III studies. We have agreement with FDA on the design of that Phase III clinical trial.

正如我們在演講中所說，我們將繼續開展非人類靈長類動物研究，以使 AVXS-101鞘內註射劑脫離臨床擱置狀態，然後我們將迅速希望通過 III 期研究推進該計劃。我們已與 FDA 就 III 期臨床試驗的設計達成協議。

Now in terms of U.S. drug pricing, we're absolutely supportive of finding a path forward to enable broader and more affordable patient access at the pharmacy counter, which would likely include reforms to the benefit design in Part D as well as elements of the design in Part B. I think we saw the outlines of that potential agreement in the Grassley-Wyden bill last year. But we are cautiously optimistic that we might be able to come to a thoughtful agreement that preserves the industry's ability to invest in innovation and then also enables broader patient access. But as you know, there are multiple moving parts. The situation is quite fluid. I think the big shift is that the industry is working to be part of the solution here, working actively with the relevant stakeholders to try to find a sensible set of legislations. Thank you, Richard.

現在就美國藥品定價而言，我們絕對支持找到一條前進的道路，讓患者能夠在藥房櫃檯獲得更廣泛、更實惠的服務，這可能包括對 D 部分中的福利設計以及設計要素進行改革在 B 部分。我認為我們在去年的格拉斯利-懷登法案中看到了該潛在協議的輪廓。但我們謹慎樂觀地認為，我們可能能夠達成一項深思熟慮的協議，以保持該行業投資於創新的能力，然後也使更廣泛的患者獲得機會。但如您所知，有多個活動部件。情況非常不穩定。我認為最大的轉變是該行業正在努力成為解決方案的一部分，與相關利益相關者積極合作，試圖找到一套合理的立法。謝謝你，理查德。

Your next question comes from the line of Laura Sutcliffe from UBS.

您的下一個問題來自瑞銀的 Laura Sutcliffe。

Firstly, excluding the impact of forward purchasing, you had both operating income growth and margin expansion this quarter. And I realize this could be difficult to pick apart. But how much were you still benefiting from cost savings that you might not ultimately get to keep in the first quarter? And secondly, for the 2 ex China filings you're expecting to make for tislelizumab this year, could you confirm whether or not you expect those to include the U.S.

首先，排除遠期採購的影響，本季度您的營業收入和利潤率都有增長。我意識到這可能很難分開。但是，您仍然從第一季度可能無法最終保留的成本節約中受益多少？其次，對於您預計今年將為 tislelizumab 提交的 2 份除中國以外的申請，您能否確認您是否希望這些申請包括美國。

So I think quickly on the second point, yes, they would include the U.S. And then on the question on cost savings, and we'll give it to Harry. Harry?

所以我很快想到第二點，是的，他們將包括美國。然後關於成本節約的問題，我們將把它交給哈利。哈利？

Yes. Thank you, Laura. So of course, we had still some lower activity in quarter 1. But when you look at the cost levels, they are pretty much in line even with prior year quarter 1 when the shutdown came mainly only in the second half of March.

是的。謝謝你，勞拉。因此，當然，我們在第一季度仍有一些較低的活動。但是當您查看成本水平時，即使關閉主要是在 3 月下半月，它們也與去年第一季度的情況基本一致。

So -- and then secondly, we are, of course, also driving new ways of working to keep the good things, if you will, of the situation to run the company more effectively. And of course, also our customer-facing colleagues have a mix of tools where face-to-face is most effective and wanted. Of course, that happens, but also the virtual and other interactions. So I would say most of the cost savings we can keep. On the other hand, some increased investments will happen in quarter 2. And of course, all of that is part of our full year guidance.

所以 - 其次，我們當然也在推動新的工作方式，以保持良好的狀態，如果你願意的話，可以更有效地運營公司。當然，我們面向客戶的同事也有多種工具，其中面對面是最有效和最需要的。當然，這種情況會發生，而且虛擬和其他交互也會發生。所以我想說我們可以保留的大部分成本節約。另一方面，第二季度將增加一些投資。當然，所有這些都是我們全年指導的一部分。

Thanks, Harry. Thanks, Laura.

謝謝，哈利。謝謝，勞拉。

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

您的下一個問題來自 Redburn 的 Simon Baker。

Two please, if I may. Firstly, on Zolgensma, going back to the European situation. Could you give us a little bit more color on where the growth was coming from in the quarter. From what you've said, it sounds like it's still the prevalent population in Germany given the timing of the U.K. and Italian reimbursement. But any color on that would be useful.

如果可以的話，請給我兩個。首先，關於佐爾根斯馬，回到歐洲局勢。您能否就本季度的增長來源向我們提供更多信息。從你所說的來看，考慮到英國和意大利的報銷時間，聽起來它仍然是德國的普遍人口。但是上面的任何顏色都會很有用。

And on to Cosentyx, perhaps you could give us your thoughts on the competitive landscape within psoriasis of Cosentyx in light of the bimekizumab data a few days ago? And secondly, on Cosentyx, also your thoughts on the Cigna debit card initiative to try and move people off Cosentyx and onto alternative products?

關於 Cosentyx，也許您可以根據幾天前的 bimekizumab 數據，談談您對 Cosentyx 銀屑病競爭格局的看法？其次，關於 Cosentyx，您對 Cigna 借記卡計劃的看法，該計劃試圖將人們從 Cosentyx 轉移到替代產品上？

Thank you, Simon. So first on Zolgensma growth, Marie-France?

謝謝你，西蒙。那麼首先是關於 Zolgensma 的增長，Marie-France？

Yes. So when we look at the European business, the incremental uptake has been mainly in Germany. And as I mentioned before, we've seen acceleration in some of the smaller markets, so Czech Republic, U.A.E. and Qatar. We have not yet seen the uptake in the U.K. and Italy, and that's what you can expect to see towards the end of the year. So as we said before, we will be moving from incident segments to additional countries where you'll see this initial bolus of patients. And then they'll transition to an incident population, as what you see in the U.S.

是的。因此，當我們查看歐洲業務時，增量吸收主要在德國。正如我之前提到的，我們已經看到一些較小的市場加速發展，例如捷克共和國、阿聯酋。和卡塔爾。我們還沒有看到英國和意大利的吸收，這就是你可以期待在今年年底看到的。因此，正如我們之前所說，我們將從事件部分轉移到其他國家/地區，您將在這些國家/地區看到最初的患者推注。然後他們將過渡到事件人群，就像你在美國看到的那樣。

So you can expect some volatility in the quarterly sales pattern because, of course, it's a onetime treatment. So every quarter, we start again from scratch, but that's what you can expect to see. We're bringing in new countries. We have a number of countries that have day 1 access agreements. And we hope to bring about 15 countries with full reimbursement by the end of 2022. And then going...

因此，您可以預期季度銷售模式會出現一些波動，因為當然，這是一次性處理。所以每個季度，我們都會從頭開始，但這就是你可以期待看到的。我們正在引進新的國家。我們有許多國家簽訂了第一天訪問協議。我們希望在 2022 年底之前為 15 個國家帶來全額報銷。然後……

And then on -- yes, Cosentyx, yes.

然後——是的，Cosentyx，是的。

Yes. So on Cosentyx, your 2 questions. So on the competitive overview, the first thing that I'd say is that we have to remember in this marketplace -- so you referred to psoriasis. The biologic penetration remains really low. In fact, when we look at psoriasis, we're talking about 15% of biologic penetration. And if we think about Cosentyx, we know that there are a lot of competitors out there, but we've shown efficacy across 4 indications.

是的。所以在 Cosentyx 上，你的 2 個問題。所以在競爭概述中，我要說的第一件事是我們必須記住這個市場 - 所以你提到了牛皮癬。生物滲透率仍然很低。事實上，當我們研究牛皮癬時，我們談論的是 15% 的生物滲透。如果我們考慮 Cosentyx，我們知道那裡有很多競爭對手，但我們已經在 4 個適應症中顯示出療效。

In psoriasis, our data shows that we clear skin in 8 out of 10 patients. And that we have strong efficacy across the axSpA spectrum. Remember that 2/3 of patients are going to have some of these manifestations.

在銀屑病中，我們的數據顯示，我們清除了 10 名患者中的 8 名的皮膚。並且我們在 axSpA 範圍內具有強大的功效。請記住，2/3 的患者會出現其中一些表現。

One other point I wanted to make is that we have 5 year-plus safety data. And the bar is very high right now on safety, especially now. So what Cosentyx offers is a tried and trusted complete treatment. In addition to that, we have strong access, not only in the U.S. but across the globe. And so I keep talking about our 3 pillars in our strategy, and it's exactly that: It's strong access, early line access that's going to allow us to grow volume and revenue in the U.S. and in the EU. We've got the geographic expansion in China with the NRDL that just came in March, so you'll see more of that in the rest of the year. Then we've got our complete profile, and we continue to have strong resonance in the marketplace with the data that we have and of course, in the future, our life cycle management program. So we've shown that we can do well despite multiple competitive entries in the psoriasis space and beyond the psoriasis space. And we're confident we can deliver double-digit growth in the year.

我想說的另一點是我們有 5 年以上的安全數據。現在的安全標準非常高，尤其是現在。因此，Cosentyx 提供的是一種久經考驗且值得信賴的完整治療方法。除此之外，我們擁有強大的訪問權限，不僅在美國，而且在全球範圍內。因此，我一直在談論我們戰略中的 3 個支柱，正是如此：強大的准入、早期的准入將使我們能夠在美國和歐盟增加銷量和收入。我們已經通過 3 月份剛剛出台的 NRDL 在中國進行了地域擴張，因此您將在今年餘下的時間裡看到更多。然後我們有了完整的檔案，我們繼續在市場上與我們擁有的數據產生強烈的共鳴，當然，在未來，我們的生命週期管理計劃。因此，我們已經證明，儘管在銀屑病領域和銀屑病領域之外有多個競爭性條目，我們仍然可以做得很好。我們有信心在今年實現兩位數的增長。

If I take your question on Cigna, yes. So the next question was on Cigna. Yes.

如果我接受你關於 Cigna 的問題，是的。所以下一個問題是關於 Cigna 的。是的。

Thanks, Marie-France. Oh yes, Cigna, yes. Please go ahead.

謝謝，瑪麗-法蘭西。哦，是的，信諾，是的。請繼續。

Yes. So I think that's a question for Cigna. But what I'll say is that we're not going to change our commitment to physicians and patients. We believe that access should enable a clinical decision between a physician and a patient. And that's why broad access is going to stay a core pillar of our strategy. But we'll always balance that with the long-term value of the brand. We have 6 potential upcoming indications, so it's our obligation to think about what drives value today, but also what drives value in our future.

是的。所以我認為這是 Cigna 的問題。但我要說的是，我們不會改變對醫生和患者的承諾。我們認為，訪問應該能夠在醫生和患者之間做出臨床決定。這就是為什麼廣泛的訪問將成為我們戰略的核心支柱。但我們將始終平衡品牌的長期價值。我們有 6 個潛在的即將出現的跡象，因此我們有義務考慮是什麼推動了今天的價值，以及什麼推動了我們未來的價值。

Your next question comes from the line of Wimal Kapadia from Bernstein.

您的下一個問題來自 Bernstein 的 Wimal Kapadia。

Wimal Kapadia from Bernstein. So can we first ask about the PSMA-617 in the VISION study following the positive headlines in March. Just given the continued changing in the standard of care in prostate cancer, I just wanted to get your thoughts on the trial design and the implications for commercial potential. Should the real comparator for VISION have been cabazitaxel in order to be of real clinical importance rather than with the best standard of care given the likes of Zytiga and Xtandi are no longer recommended in that setting. So I appreciate it's quite a fluid situation when it makes -- when it comes to trial design, but just your thoughts on commercial impact would be great.

來自伯恩斯坦的 Wimal Kapadia。那麼，在 3 月份的積極頭條新聞之後，我們能否首先詢問 VISION 研究中的 PSMA-617。鑑於前列腺癌護理標準的持續變化，我只是想了解您對試驗設計及其對商業潛力的影響的看法。 VISION 的真正比較器是否應該是卡巴他賽，以便具有真正的臨床重要性，而不是提供最佳護理標準，因為在這種情況下不再推薦 Zytiga 和 Xtandi 之類的藥物。因此，我很欣賞它在試驗設計方面的非常不穩定的情況，但是您對商業影響的想法會很棒。

And then my second question is just on ligelizumab and the upcoming Phase III readout in CSU. Just curious on your thoughts on your level of confidence for that readout later this year. How quickly could we actually see switching from Xolair should we see positive data. And can you just provide some context on what proportion of Xolair sales come from CSU today?

然後我的第二個問題是關於 ligelizumab 和即將在 CSU 中進行的 III 期讀數。只是好奇您對今年晚些時候對該讀數的信心水平的想法。如果我們看到積極的數據，我們實際上能多快看到從 Xolair 轉換。您能否提供一些關於今天 Xolair 銷售額中來自 CSU 的比例的背景信息？

Yes. Thanks, Wimal. And thanks also for your initiation of coverage and your very comprehensive report a few weeks back. So first on PSMA-617, I'll move to Susanne on the commercial potential on the trial design.

是的。謝謝，維馬爾。還要感謝您在幾週前發起的報導和非常全面的報告。所以首先在 PSMA-617 上，我將轉向 Susanne，討論試驗設計的商業潛力。

Yes. So maybe let me start with the trial design. So just to remind you what the setting was for the VISION trial, so it was in progressive metastatic castration-resistant prostate cancer with at least one line of prior androgen therapy and at least one but not more than 2 lines of taxane-based chemotherapy. And we felt in this setting standard of care is the best comparator. It's really a setting where there is limited options and this setting of very high unmet medical need. So we believe it is very strong data. And I think the fact that we were really showing positive data on both radiographic PFS and OS I think is demonstrating that.

是的。所以也許讓我從試驗設計開始。所以只是提醒你 VISION 試驗的設置是什麼，所以它是在進行性轉移性去勢抵抗性前列腺癌中，至少接受過一種雄激素治療和至少一種但不超過 2 種基於紫杉烷的化療。我們覺得在這個設置中，護理標準是最好的比較器。這確實是一個選擇有限且醫療需求未得到滿足的環境。所以我們認為這是非常強大的數據。而且我認為我們確實在放射學 PFS 和 OS 上都顯示出積極的數據這一事實證明了這一點。

And as I said, the commercial potential in this area is still significant as prostate cancer is the second-largest cancer indication. This setting, of course, is in late lines, but we still believe there's very high medical need and lutetium-PSMA way will offer a very, very attractive treatment option. And when you just look into the setting, think again that the majority of these patients will be metastatic, have a very low survival -- 5-year survival rate. So therefore, it is a significant pool of patients.

正如我所說，該領域的商業潛力仍然很大，因為前列腺癌是第二大癌症適應症。當然，這種設置處於後期階段，但我們仍然相信醫療需求非常高，镥-PSMA 方式將提供非常非常有吸引力的治療選擇。當你只看環境時，再想想這些患者中的大多數將是轉移性的，存活率非常低——5年存活率。因此，它是一個重要的患者群體。

Maybe I'll just add, as we noted in the presentation, we've already initiated or will soon initiate a range of earlier stage prostate cancer studies, which will enable us, if successful, to rapidly broaden the indication base for PSMA-617.

也許我會補充一下，正如我們在演示文稿中所指出的，我們已經或將很快啟動一系列早期前列腺癌研究，如果成功，這將使我們能夠迅速擴大 PSMA-617 的適應症基礎.

So on ligelizumab, on the clinical program and our confidence, maybe John. And then maybe Marie-France on the contribution of CSU and the ability to switch from Xolair. So John?

所以關於ligelizumab，關於臨床項目和我們的信心，也許是約翰。然後也許 Marie-France 關於 CSU 的貢獻以及從 Xolair 轉換的能力。那麼約翰?

Sure. Yes. Thanks. Thanks for the question. As you know, we moved into the Phase III program based on the Phase II head-to-head study that we had against Xolair, which was published in the New England Journal. Based on that Phase II study, what we saw was 42% symptom-free with ligelizumab versus 26% in omalizumab, which was a significant difference. And scientifically, as we think about that, ligelizumab recognizes a different epitope on the IgE molecule for Xolair, and that's the confidence that we have, and more specifically binds on the FcepsilonRI effector cells. And based on the stack, we've moved into the 2 PEARL -- 2 studies, PEARL 1 and PEARL 2. We expect to get those readouts by the end of the year and the early part of next year as we continue to accrue the end points.

當然。是的。謝謝。謝謝你的問題。如您所知，我們基於針對 Xolair 的 II 期頭對頭研究進入了 III 期計劃，該研究發表在《新英格蘭雜誌》上。根據那項 II 期研究，我們看到 ligelizumab 組 42% 無症狀，而 omalizumab 組為 26%，這是一個顯著差異。從科學上講，當我們考慮到這一點時，ligelizumab 識別 Xolair 的 IgE 分子上的不同表位，這就是我們的信心，並且更具體地與 FcepsilonRI 效應細胞結合。根據堆棧，我們進入了 2 PEARL - 2 項研究，PEARL 1 和 PEARL 2。隨著我們繼續積累終點。

On the population and opportunity, maybe turn it...

關於人口和機會，也許可以轉...

Yes, we can go to Marie-France. Marie-France?

是的，我們可以去瑪麗-法蘭西。瑪麗-法蘭西？

So the first thing to point out is that the biologic penetration in this market space is also really low. We currently estimate that less than 30% of patients are on Xolair, and that's probably optimistic. And what we know is that we've got about 1.3 million CSU patients in the top 11 countries that are still not adequately controlled. So this is a big opportunity This product is showing to differentiate itself significantly and an opportunity for us to bring this product to a much broader population, which right now is really underserved with antihistamines.

所以首先要指出的是，這個市場空間的生物滲透率也很低。我們目前估計只有不到 30% 的患者使用 Xolair，這可能是樂觀的。我們所知道的是，在前 11 個國家中，我們有大約 130 萬 CSU 患者仍未得到充分控制。所以這是一個巨大的機會 該產品顯示出顯著的差異化，也是我們將這種產品推廣到更廣泛的人群的機會，而這些人群目前確實缺乏抗組胺藥。

Terrific. Thanks, Marie-France. So for the remaining questions, if I could ask if we could limit yourself to one question, that would be great as we have a number of people in the queue. So next question, operator?

了不起。謝謝，瑪麗-法蘭西。所以對於剩下的問題，如果我可以問我們是否可以將自己限制在一個問題上，那將是很好的，因為我們有很多人在排隊。那麼下一個問題，運營商？

Your next question comes from the line of Florent Cespedes from Société Générale.

您的下一個問題來自 Société Générale 的 Florent Cespedes。

For Susanne on Kisqali, how would you explain the difference on the dynamic of the U.S. versus Europe markets? And why Europe is much more dynamic than the U.S.? And how do you see the U.S. market, breast cancer market dynamic going forward?

對於 Kisqali 上的 Susanne，您如何解釋美國與歐洲市場動態的差異？為什麼歐洲比美國更有活力？您如何看待美國市場、乳腺癌市場的未來動態？

Susanne?

蘇珊？

Yes. Thank you, Florent. So as I said, Kisqali globally was growing 19%. And as you rightly point out, there was very strong growth ex U.S., especially in the EU, while the sales were more or less flattish or slightly declining in the U.S. And I think the reason is really very different market dynamics. That in the U.S., the market certainly is already quite penetrated with CDK4/6 inhibitors. And when you look at the impact of COVID, you saw that NBRx, for example, in February was down 16%, and this has continued now since the pandemic started. And this is now already impacting TRx, going down minus 4%.

是的。謝謝你，弗洛倫特。正如我所說，Kisqali 全球增長了 19%。正如您正確指出的那樣，美國以外的市場增長非常強勁，尤其是在歐盟，而美國的銷售額或多或少持平或略有下降。我認為原因確實是非常不同的市場動態。在美國，CDK4/6 抑製劑的市場肯定已經相當普及。例如，當您查看 COVID 的影響時，您會看到 NBRx 在 2 月份下降了 16%，並且自大流行開始以來這種情況一直在持續。現在這已經影響了 TRx，下降了負 4%。

So of course, our growth would come from new patients, and that's hard to get if less new patients coming in. While in Europe, overall penetration of CDK4/6 is much slower, so dynamics there are more active and, therefore, we could capture more patients there.

因此，當然，我們的增長將來自新患者，如果新患者減少，這將很難實現。雖然在歐洲，CDK4/6 的整體滲透要慢得多，因此那裡的動態更加活躍，因此，我們可以在那裡捕獲更多的患者。

So overall, as I said, Kisqali, with the strong OS data, we feel is very well differentiated. We keep on focusing executing our growth brands. And we remain confident also for the U.S. that when patients will come back and things will open up more, that we capture again strong growth.

所以總的來說，正如我所說，Kisqali 擁有強大的操作系統數據，我們覺得差異化非常好。我們繼續專注於執行我們的增長品牌。我們也對美國充滿信心，當患者回來並且事情會更加開放時，我們會再次獲得強勁的增長。

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 Richard Vosser。

Just a question on the ophtha brand erosion and just when we should think about that bottoming out and the growth of the ophthalmology franchise going forward.

只是關於 ophtha 品牌侵蝕的問題，以及我們何時應該考慮觸底反彈以及眼科特許經營權的未來增長。

Thank you, Richard. So on ophthalmology dynamics, Marie-France? I guess also referring to front of the eye as well. I would note Xiidra -- a strong Xiidra performance as well really on the quarter. So...

謝謝你，理查德。那麼關於眼科動力學，Marie-France？我想也指眼前。我會注意到 Xiidra——Xiidra 在本季度的表現也很強勁。所以...

Right. I was going to mention that. So we do see -- obviously, we've seen a huge impact in this space because of COVID. So there's a combination of factors. So we have seen some loss of exclusivity, which is obviously something that we anticipated over our strat plan period. And then, of course, there was the COVID impact, which really hit the entire ophtha portfolio, as you know, starting with the anti-VGEFs, which nicely recuperated during the year. And you see them off to solid performance across the board in 2021.

正確的。我正要提到這一點。所以我們確實看到了——顯然，由於 COVID，我們已經看到了這個領域的巨大影響。所以有多種因素的組合。因此，我們已經看到排他性有所喪失，這顯然是我們在戰略計劃期間所預期的。然後，當然，還有 COVID 的影響，它確實影響了整個 ophtha 產品組合，如您所知，從抗 VGEF 開始，在這一年中得到了很好的恢復。您會看到它們在 2021 年全面實現穩健表現。

We still see a suppression in the marketplace although that's starting to pick up. And what I will point out is our front of the eye portfolio, or namely in Xiidra, we do see very encouraging data. I mean we had to relaunch that brand, as you know. But we also know it's a big market, right? 32 million people with dry eye disease, and only 1.6 million of them are on a prescription drug. So we had a good quarter with Xiidra, 28% of NBRx share. And it just shows that if you have the share of voice, if you have the right campaign, then it's worth investing in this space.

儘管這種情況開始回升，但我們仍然看到市場受到抑制。我要指出的是我們的眼前投資組合，或者在 Xiidra，我們確實看到了非常令人鼓舞的數據。我的意思是我們不得不重新推出那個品牌，你知道的。但我們也知道這是一個很大的市場，對吧？ 3200 萬人患有乾眼症，其中只有 160 萬人服用處方藥。所以我們在 Xiidra 的季度表現不錯，佔 NBRx 份額的 28%。它只是表明，如果你有發言權，如果你有正確的活動，那麼在這個領域投資是值得的。

Terrific. Thank you, Marie-France and Richard.

了不起。謝謝你，瑪麗-法蘭西和理查德。

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

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

Yes. This is [Richard Wagner] on behalf of Tim at Wolfe Research. It's a question on Kisqali. Could you speak about what you're seeing in the U.S. in terms of rebating in this oral oncologic category. Our understanding is that the rebates are stepping up. Presumably, that is driven by Pfizer trying to hang on to market share. What's the outlook for the net price trends in this category? And where -- how would those trends, in particular, impact Kisqali, which does not have the volume of eye brands and does not yet have the adjuvant data.

是的。我是 [Richard Wagner] 代表 Wolfe Research 的 Tim。這是關於 Kisqali 的問題。您能否談談您在美國看到的關於口腔腫瘤學類別的回扣的情況。我們的理解是回扣正在增加。據推測，這是由輝瑞公司試圖保住市場份額所推動的。該類別的淨價格趨勢前景如何？以及在哪裡——這些趨勢將如何影響 Kisqali，它沒有眼部品牌的數量，也沒有輔助數據。

Thanks, [Richard]. So Susanne, on Kisqali -- or CDK4/6 rebating trends.

謝謝，[理查德]。所以 Susanne，關於 Kisqali 或 CDK4/6 回扣趨勢。

Yes, sure. So I wouldn't want to comment on that. Maybe let me just reemphasize what is our strategy. Certainly, we see that Kisqali has the best OS data and also has demonstrated now longest OS combining all the Phase III trials. And that keeps us confident that if we focus continued on execution, we will also see continued momentum.

是的，當然。所以我不想對此發表評論。也許讓我再強調一下我們的策略是什麼。當然，我們看到 Kisqali 擁有最好的 OS 數據，並且還展示了現在最長的 OS，結合了所有 III 期試驗。這讓我們有信心，如果我們繼續專注於執行，我們也會看到持續的動力。

We get very positive feedback from HCPs, and we see that they are changing now their treatment patterns, that more and more are willing to list Kisqali. So I believe our focus needs to be on differentiation, on continued execution of our growth brands. And therefore, I still believe Kisqali is an important growth driver for us, and I remain very confident in the brand.

我們從 HCP 那裡得到了非常積極的反饋，我們看到他們現在正在改變他們的治療模式，越來越多的人願意列出 Kisqali。因此，我認為我們的重點需要放在差異化上，繼續執行我們的成長品牌。因此，我仍然相信 Kisqali 是我們重要的增長動力，我對這個品牌仍然非常有信心。

Thank you, Susanne.

謝謝你，蘇珊。

Your next question comes from the line of Mike Nedelcovych from Cowen.

您的下一個問題來自 Cowen 的 Mike Nedelcovych。

I'm curious on Entresto. It looks like the data in the post-MI setting trended toward improvement despite missing the primary end point, but the readout is listed as neutral on the slide. So I'm just wondering, should we take that to mean that filing in that indication might still be on the table?

我對Entresto很好奇。儘管缺少主要終點，但 MI 後設置中的數據似乎趨於改善，但讀數在幻燈片上列為中性。所以我只是想知道，我們是否應該認為這意味著該指示中的文件可能仍然在桌面上？

Yes. I'll just quickly take that. We need to discuss with the regulatory authorities, and we'll present the full data in ACC where you can see both the primary and secondary end points. But then the question on the table, of course, is we demonstrated a positive trend versus an established standard of care in ramipril. But it was a superiority study. So I think we'll need to work through with the regulators what's possible in terms of any sort of indication in the label or any data in the label. But we'll take those steps and we'll present the data at ACC.

是的。我會很快接受的。我們需要與監管機構討論，我們將在 ACC 中提供完整的數據，您可以在其中看到主要和次要終點。但是，當然，擺在桌面上的問題是，與雷米普利的既定護理標準相比，我們表現出積極的趨勢。但這是一項優越性研究。因此，我認為我們需要與監管機構就標籤中的任何類型的指示或標籤中的任何數據進行合作。但我們會採取這些步驟，我們會在 ACC 上展示數據。

And the final question comes from the line of Peter Welford from Jefferies.

最後一個問題來自 Jefferies 的 Peter Welford。

A quick question on Sandoz again. I wonder if it's possible for you to quantify the impact of the termination of your oral solids partnerships, which I guess is somewhat of a one-off. And just thinking about then the Sandoz business and getting it back to growth and margins, how should we think about the potential for disposing parts of that business or slimming the portfolio down? I know you've tried this before, but clearly to return to growth and margins, the other way is to slim down the sales line. Is that even viable with the business portfolio that you have?

又是一個關於 Sandoz 的快速問題。我想知道您是否有可能量化終止您的口服固體合作夥伴關係的影響，我想這有點一次性。想想山德士的業務並讓它恢復增長和利潤率，我們應該如何考慮出售部分業務或縮減投資組合的潛力？我知道你以前嘗試過，但顯然是為了恢復增長和利潤，另一種方法是縮小銷售線。這對您擁有的業務組合是否可行？

Thanks, Peter. And Richard Saynor on the Sandoz U.S. business and the legacy -- well, the oral solids and dermatology business.

謝謝，彼得。還有 Richard Saynor 談山德士美國業務和遺產——嗯，口服固體和皮膚科業務。

Yes. Thank you. Thank you, Peter. So yes, you're right. I mean clearly, we've terminated or ended a number of the partnership relationships, and that's really washing through from the end of last year really pretty much to the end of this year. So a lot of the decline that you see in the oral solids business is really related to that. But hopefully, that will wash out by the end of this year.

是的。謝謝你。謝謝你，彼得。所以，是的，你是對的。我的意思很清楚，我們已經終止或結束了一些合作關係，從去年年底到今年年底，這真的很明顯。因此，您在口服固體藥物業務中看到的很多下滑確實與此有關。但希望這將在今年年底前消失。

And then really, I see the U.S. business in sort of 3 district chunks: you have the core business, the injectables, the biologics and the ophtha business, which really has a strong momentum and potential for growth as we launch new products going into the end of '22 and '23. We're currently looking at how we strengthen and stabilize the oral solids business once that washout phase has cleared with both in-house development and rebuilding that capability and then looking at also BD and M&A to strengthen it.

然後真的，我看到美國業務分為 3 個區域塊：你有核心業務、注射劑、生物製劑和 ophtha 業務，隨著我們推出新產品進入'22 和 '23 結束。我們目前正在研究如何通過內部開發和重建能力來加強和穩定口服固體藥物業務，然後再考慮通過 BD 和併購來加強它。

And then the derma piece, already, we've cleaned up a lot of the derma business. We divested some of those elements over the last month, and the remaining is relatively stable and accretive to the overall business. So yes, a lot of moving pieces, but we've got a clear plan going forward.

然後是真皮片，我們已經清理了很多真皮業務。我們在上個月剝離了其中一些元素，其餘元素相對穩定且對整體業務具有增值作用。所以，是的，有很多動人的部分，但我們有一個明確的計劃。

Terrific. Thanks, Richard. And thanks, everyone, for your questions today. Maybe just to take a step back, I think it's worth noting when you look at the longer-term growth profile of the company, our key, again, drivers, Cosentyx, Entresto, Zolgensma, Kesimpta are all demonstrating they have the outlook and the potential to really enable us to grow consistently through 2025, as Harry outlined.

了不起。謝謝，理查德。感謝大家今天提出的問題。也許只是退後一步，我認為當您查看公司的長期增長概況時值得注意的是，我們的關鍵，再次，驅動程序，Cosentyx，Entresto，Zolgensma，Kesimpta 都證明了他們有前景和正如哈利所概述的那樣，有潛力真正使我們能夠在 2025 年持續增長。

On top of that, we continue to expect to be able to bring inclisiran to broad groups of patients in the U.K. and the U.S. well ahead of the outcomes study, giving inclisiran significant potential even ahead of the outcomes data, which we now expect in '26. With the Kisqali adjuvant and our continued efforts in Beovu, you have a broad range of products in hand to drive that growth for the next few years.

最重要的是，我們繼續期望能夠在結果研究之前將 inclisiran 帶給英國和美國的廣泛患者群體，甚至在我們現在預計的結果數據之前賦予 inclisiran 巨大的潛力。 26.借助 Kisqali 佐劑和我們在 Beovu 的持續努力，您將擁有廣泛的產品來推動未來幾年的增長。

Then on top of that, you have a deep mid-stage pipeline, where we continue to show progress, multiple assets that could be multibillion-dollar potential assets to drive our longer-term growth. You see already the first possibilities with Lu-PSMA, and we hope to demonstrate with further readouts over the course of this year, the potential of that pipeline. Continued margin progression and aspiration and demonstration of leadership in ESG.

然後最重要的是，你有一個很深的中期管道，我們繼續展示進展，多種資產可能是數十億美元的潛在資產，以推動我們的長期增長。您已經看到了 Lu-PSMA 的第一個可能性，我們希望在今年進一步展示該管道的潛力。持續的利潤增長和願望以及在 ESG 方面的領導力展示。

So I think the story is taking shape, and we look forward to continuing to attract long-term investors to our company, to our stock and our overall vision to reimagine medicine. So thank you all very much for joining the call, and we'll look forward to speaking again soon.

所以我認為這個故事正在形成，我們期待繼續吸引長期投資者到我們的公司、我們的股票和我們重新構想醫學的總體願景。非常感謝大家加入電話會議，我們期待很快再次發言。

Thank you. That does conclude your call and webcast for today. Thank you all for participating. And you may now disconnect.

謝謝你。這確實結束了您今天的電話和網絡廣播。謝謝大家的參與。您現在可以斷開連接。