Novartis AG (NVS) 2022 Q1 法說會逐字稿

Good morning and good afternoon, and welcome to the Novartis Q1 2022 Results Release Conference Call and Live Webcast. (Operator Instructions) And the conference is being recorded. (Operator Instructions) A recording of the conference call, including the Q&A session, will be available on our website shortly after the call ends. (Operator Instructions)

早上好，下午好，歡迎來到諾華 2022 年第一季度業績電話會議和網絡直播。 （操作員說明）會議正在錄製中。 （操作員說明）電話會議的錄音，包括問答環節，將在電話會議結束後不久在我們的網站上提供。 （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, everybody, and good morning and good afternoon to all participants. Thank you for joining us today for Novartis's quarter 1 2022 results.

非常感謝大家，祝所有參與者早上好，下午好。感謝您今天加入我們，了解諾華 2022 年第一季度的業績。

Before we start, just wanted to go through the safe harbor statements. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause the 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，只是想通過安全港聲明。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 hand across to Vas.

有了這個，我將交給 Vas。

Thank you, Samir, and thanks everyone for joining our conference call today. If we could move forward a few slides.

謝謝你，薩米爾，感謝大家今天參加我們的電話會議。如果我們可以向前推幾張幻燈片。

So with me today, I have Harry Kirsch, our Chief Financial Officer; and Karen Hale, our Chief Legal Officer.

所以今天和我在一起的是我們的首席財務官 Harry Kirsch；和我們的首席法律官 Karen Hale。

If we go to Slide 4. Overall, the quarter came out with a solid start for Novartis across all of our 4 key pillars. From a growth standpoint, good sales growth both at the IM and Sandoz and, of course, the overall group level.

如果我們轉到幻燈片 4。總體而言，本季度諾華在我們所有的 4 個關鍵支柱方面都取得了良好的開端。從增長的角度來看，IM 和 Sandoz 的銷售增長良好，當然還有整個集團層面。

Good productivity, group core operating income, up 9% on a constant currency basis as well as a solid result in both IM and Sandoz. Some important innovation milestones, I'll go through those in a bit more detail. And we also continue to advance our ESG agenda in AMR as well as Access to Medicines agreements in Africa. So I think a solid quarter that we can build on over the course of this year.

良好的生產力、集團核心營業收入、按固定匯率計算增長 9%，以及 IM 和 Sandoz 的穩健業績。一些重要的創新里程碑，我將更詳細地介紹這些里程碑。我們還繼續推進我們在 AMR 方面的 ESG 議程以及非洲的藥品獲取協議。因此，我認為我們可以在今年的整個過程中建立一個穩固的季度。

Moving to the next slide. Our Innovative Medicines sales grew across both our U.S. and ex U.S. geographies, 3% in the U.S., 5% ex-U.S. in constant currencies, with growth drivers now accounting for 56% of our IM sales. Growth of those -- growth drivers, up 21% quarter-over-quarter. So a nice demonstration that we continue to replace our sales base with newer and newer products.

轉到下一張幻燈片。我們在美國和美國以外地區的創新藥物銷售額均增長，美國增長 3%，美國以外地區增長 5%。以固定匯率計算，增長驅動因素現在占我們 IM 銷售額的 56%。這些增長——增長驅動因素，環比增長 21%。這是一個很好的證明，我們繼續用更新的產品取代我們的銷售基地。

Now moving to Slide 6. We saw strong performance on our key growth drivers, the 6 brands we've been consistently highlighting, and I'll talk about them in a bit more detail. But you can see really across these key brands growth that ranged from the high single digit to the double-digit range. So again, pleased with the broad-based performance. Of course, there were pockets of weakness, and we can talk more about that. But overall, we're pleased that we're off to this solid start on the key brands.

現在轉到幻燈片 6。我們看到了我們的主要增長驅動力的強勁表現，我們一直強調的 6 個品牌，我將更詳細地討論它們。但是你可以看到這些關鍵品牌的增長從高個位數到兩位數不等。再次，對廣泛的表現感到滿意。當然，也有一些弱點，我們可以談論更多。但總的來說，我們很高興我們在關鍵品牌上取得了良好的開端。

But let's go a bit deeper on the 6 key brands. So moving to the next slide on Slide 7. You see that on Cosentyx, Entresto, Zolgensma, Kisqali, Kesimpta and Leqvio, we had good growth on the major brands that we really believe will drive our midterm sales performance and, of course, continue to maintain our peak sales guidance on these brands.

但是，讓我們更深入地了解 6 個關鍵品牌。因此，轉到幻燈片 7 的下一張幻燈片。您會看到，在 Cosentyx、Entresto、Zolgensma、Kisqali、Kesimpta 和 Leqvio，我們在主要品牌上取得了良好的增長，我們相信這些主要品牌將推動我們的中期銷售業績，當然，還會繼續以維持我們對這些品牌的最高銷售指導。

Importantly as well, Kesimpta has now demonstrated in Q1 the potential we expect of this brand, to really reach that multibillion-dollar potential with very strong growth in the quarter. We'll talk more about that.

同樣重要的是，Kesimpta 現在已經在第一季度展示了我們對該品牌的預期潛力，在該季度實現了非常強勁的增長，真正達到了數十億美元的潛力。我們將對此進行更多討論。

And with Leqvio, continue to build the solid foundation base for what will be a multiyear journey to get to the multibillion-dollar sales potential. But I think the initial foundational elements are starting to come in to play. So again, it will be a longer-term journey for this brand.

借助 Leqvio，繼續為實現數十億美元銷售潛力的多年旅程奠定堅實的基礎。但我認為最初的基礎元素開始發揮作用。因此，對於這個品牌來說，這將是一個長期的旅程。

Moving to Slide 8. And going to each one of these brands, brand-by-brand.

轉到第 8 張幻燈片。逐個品牌地訪問這些品牌中的每一個。

First with respect to Cosentyx, double-digit sales growth, 12% on the quarter, really driven by our ex-U.S. performance. When you look at the specifics on the growth momentum, we saw steady volume growth in the U.S. and EU. We have 700,000 patients now across our 5 indications treated worldwide since launch. Very good performance in rheumatology across geographies.

首先是 Cosentyx，銷售額實現兩位數增長，本季度增長 12%，真正受到我們前美國市場的推動。表現。當您查看增長勢頭的具體細節時，我們看到美國和歐盟的銷量穩步增長。自推出以來，我們在全球範圍內接受了 5 個適應症治療的 700,000 名患者。在各個地區的風濕病學方面表現非常出色。

We expect double-digit growth in '22, driven by our China market expansion. Year-to-date, our China performance has been good. We also will, in the medium term, be driven by our ability to get new indications online. We're on track for our hidradenitis suppurativa submission this year, and we do expect CHMP decision on a couple of additional indications later in quarter 2. So we confirm our $7 billion-plus peak sales expectations for Cosentyx.

在我們中國市場擴張的推動下，我們預計 22 年將實現兩位數的增長。年初至今，我們在中國的表現一直不錯。在中期內，我們還將受到我們在線獲得新適應症的能力的驅動。我們今年有望提交化膿性汗腺炎，我們確實預計 CHMP 將在第二季度晚些時候對幾個額外的適應症做出決定。因此，我們確認了對 Cosentyx 超過 70 億美元的峰值銷售預期。

Moving to the next slide. Entresto had an outstanding first quarter, growing 42% on the quarter, driven by both U.S. and ex-U.S. performance. You can see here the U.S. weekly NBRx showing a nice steep ramp as we come out -- particularly as we come out of the pandemic period.

轉到下一張幻燈片。 Entresto 第一季度表現出色，在美國和美國以外地區的推動下，本季度增長了 42%。表現。你可以在這裡看到美國每週 NBRx 在我們出來時顯示出一個很好的陡峭斜坡 - 特別是當我們走出大流行期時。

This growth has been driven across hospitals, cardiology and primary care, so really broad based in the U.S., primarily driven by reduced ejection fraction, especially with the new guidelines that are now in place, but also supported by the preserved ejection fraction indication. We have strong demand growth in Europe for the brand. And in China as well as Japan, the launch of our hypertension indications and the NRDL listing in China have helped drive this growth.

這種增長是由醫院、心髒病學和初級保健部門推動的，在美國的基礎非常廣泛，主要是由於射血分數降低，特別是在現在實施的新指南的情況下，但也得到了保留射血分數指示的支持。我們在歐洲對該品牌的需求增長強勁。在中國和日本，我們推出的高血壓適應症和在中國的 NRDL 上市幫助推動了這一增長。

So longer term, we expect the continued development of evidence base, the continued drive of the guidelines that place [RNE] as a first choice for physicians treating reduced ejection fraction heart failure as well as for further penetration in China and Japan to drive the momentum for Entresto.

因此，從長遠來看，我們預計證據基礎的持續發展，將 [RNE] 作為醫生治療射血分數降低心力衰竭的首選指南的持續推動，以及在中國和日本的進一步滲透以推動這一勢頭為Entresto。

Moving to the next slide. Zolgensma grew 18% on the quarter, with increasing access outside of the United States. The Q1 highlights were really the ex-U.S., where we had sales growth 32% in constant currency. While, the U.S. remains steady as we continue to drive up the newborn screening rates. So right now, we have over 2,000 patients treated worldwide, which I think demonstrates the profile of this gene therapy and the confidence providers are having using this medicine.

轉到下一張幻燈片。 Zolgensma 本季度增長 18%，美國以外地區的訪問量增加。第一季度的亮點實際上是美國以外的地區，我們的銷售額增長了 32%（按固定匯率計算）。同時，隨著我們繼續提高新生兒篩查率，美國保持穩定。所以現在，我們在全球有超過 2,000 名患者接受治療，我認為這證明了這種基因療法的概況以及提供者使用這種藥物的信心。

In the future, our growth will be driven by continuing to penetrate in the U.S. the under 2, really getting to high market share. We expect to have over 90% of children who are diagnosed in newborn screening receiving Zolgensma, that's our goal, and continuing to drive up that newborn screening in the EU above 25%.

未來，我們的增長將由繼續滲透到美國 2 歲以下兒童，真正獲得高市場份額來推動。我們預計超過 90% 的新生兒篩查被診斷出的兒童接受 Zolgensma，這是我們的目標，並繼續將歐盟的新生兒篩查提高到 25% 以上。

Our next phase of data studies or data generation is on track, the STEER study with intrathecal in older children is currently enrolling. The STRENGTH study to further profile in the IV setting is starting in the second half. We also rolled out some additional data at MDA, which supports the overall profile of Zolgensma IV. So this will be a steady ramp towards our goal to be towards the $2 billion product over time. But overall, the signs and signals are good.

我們下一階段的數據研究或數據生成正在進行中，針對年齡較大的兒童進行鞘內註射的 STEER 研究目前正在招募中。在 IV 設置中進一步分析的 STRENGTH 研究將從下半年開始。我們還在 MDA 推出了一些額外的數據，這些數據支持 Zolgensma IV 的整體概況。因此，隨著時間的推移，這將是我們朝著 20 億美元產品目標穩步邁進的一步。但總的來說，跡象和信號都很好。

Moving to the next slide. Kisqali demonstrated -- delivered 28% growth on the quarter, primarily driven again by ex-U.S. performance. The market trends show a recovery to pre-COVID levels for CDK4/6 TRx, but we continue to see a suppression in the NBRx part of the market. And so we'll have to continue to watch to see that recovery, which will be critical for us because a lot of our growth is dependent on new-to-brand patients.

轉到下一張幻燈片。 Kisqali 展示了——本季度實現了 28% 的增長，這主要是由美國以外地區再次推動的。表現。市場趨勢顯示 CDK4/6 TRx 恢復到 COVID 之前的水平，但我們繼續看到 NBRx 部分市場受到抑制。因此，我們將不得不繼續觀察這種複蘇，這對我們來說至關重要，因為我們的很多增長都依賴於新品牌患者。

Kisqali's growth in the U.S. is in line with market, but in Europe, we continue to grow ahead of market. And I'll speak more about the NATALEE adjuvant study update that we provided today in an upcoming slide.

Kisqali 在美國的增長與市場一致，但在歐洲，我們的增長繼續領先於市場。我將更多地談論我們今天在即將發布的幻燈片中提供的 NATALEE 輔助研究更新。

Moving to Slide 12. Now turning to Kesimpta. Kesimpta really, I think, had a strong quarter. We have 20,000 patients treated. Over 60% are naive or first switch. In the U.S., we see really strong growth dynamics. Despite a suppressed market, you can see in the upper left-hand side of the slide, the U.S. MS market growth remains below its pre-COVID levels. Nonetheless, we see Kesimpta continuing to gain momentum.

轉到幻燈片 12。現在轉到 Kesimpta。我認為 Kesimpta 確實有一個強勁的季度。我們治療了 20,000 名患者。超過 60% 的人天真或第一次轉換。在美國，我們看到了非常強勁的增長動力。儘管市場受到抑制，但您可以在幻燈片的左上角看到，美國 MS 市場的增長仍低於 COVID 之前的水平。儘管如此，我們看到 Kesimpta 繼續獲得動力。

And now outside of the United States, we're approved in 68 countries. So over the course of this year and really starting in 2023, we would expect the ex-U.S. contributions to the brand to start to increase.

現在在美國以外，我們在 68 個國家獲得了批准。因此，在今年和真正從 2023 年開始的過程中，我們預計前美國對品牌的貢獻開始增加。

We again rolled out additional data in the quarter now at 4 years out showing the ability to reduce disability worsening, with stable IgG levels as well as data that supports the use of Kesimpta in patients who need to be treated with COVID-19 vaccination.

我們在本季度再次推出了 4 年的額外數據，顯示了減少殘疾惡化的能力、穩定的 IgG 水平以及支持在需要接受 COVID-19 疫苗接種的患者中使用 Kesimpta 的數據。

So overall, I think a strong start to the quarter, a lot of good momentum with Kesimpta, and we'll look forward to delivering that momentum or accelerating that momentum over the course of the year.

因此，總的來說，我認為本季度開局強勁，Kesimpta 勢頭良好，我們期待在這一年中實現這種勢頭或加速這種勢頭。

Now moving to the next slide, Slide 13. Turning to Leqvio. Again, early days, particularly in the U.S., but I think the leading indicators point to the foundations being put in place to have this brand become a very significant brand for the company.

現在轉到下一張幻燈片，幻燈片 13。轉向 Leqvio。同樣，早期，特別是在美國，但我認為領先指標表明該品牌已成為公司非常重要的品牌。

We reached over 90% of HCPs. We have good unaided brand awareness. Our DTC is now initiated. We've also established access in over -- it's actually over 50 now 200 -- of the 200 prioritized systems. So it's 35 on the slide, but we're up to 50, have ordered Leqvio. Our focus very much is in driving more depth in those accounts. We have 55% of our alternative injection sites accounts now have purchased Leqvio, 30% repeat orders. And importantly, our permanent J-code has been granted and will go into effect on July 1. So all of this to say that the foundations are in place for the second half. In the second half of this year to begin to see more acceleration in growth for Leqvio, going into what we expect to see further acceleration in the coming years.

我們接觸了超過 90% 的 HCP。我們擁有良好的獨立品牌知名度。我們的 DTC 現在已啟動。我們還在 200 個優先系統中建立了超過 50 個現在 200 個的訪問權限。所以幻燈片上有 35 個，但我們最多有 50 個，訂購了 Leqvio。我們的重點是推動這些賬戶的更深入。我們現在有 55% 的替代注射站點帳戶購買了 Leqvio，30% 的重複訂單。重要的是，我們的永久 J 代碼已獲得批准，並將於 7 月 1 日生效。所以所有這一切都表明下半年的基礎已經到位。今年下半年，Leqvio 的增長將開始加速，我們預計未來幾年將進一步加速。

Now moving to the next slide. I just wanted to say a word on our 2 recent launches in the U.S. Scemblix, our BCR-ABL inhibitor, STAMP inhibitor showed nice performance in the quarter in the third-line setting. Here, you can see our NBRx share has reached 20% through February. Still small numbers, but I think it points to the potential of this medicine given its strong efficacy and safety profile. We're up to 49% third-line patient share. And our first line Phase III study is now enrolling ahead of plan. So we remain optimistic that we can deliver an over $500 million brand in the third-line setting, but our focus in the longer term is hopefully with positive data move into the frontline setting.

現在轉到下一張幻燈片。我只想說一下我們最近在美國推出的 2 次 Scemblix，我們的 BCR-ABL 抑製劑 STAMP 抑製劑在本季度的三線設置中表現出色。在這裡，您可以看到我們的 NBRx 份額截至 2 月份已達到 20%。數量仍然很少，但我認為它指出了這種藥物的潛力，因為它具有很強的療效和安全性。我們的三線患者份額高達 49%。我們的一線 III 期研究現在正在提前註冊。因此，我們仍然樂觀地認為我們可以在三線環境中提供價值超過 5 億美元的品牌，但我們長期關注的重點是希望將積極的數據轉移到一線環境中。

Moving to the next slide with Pluvicto. So we at the -- towards the end of the quarter, I received approval for Pluvicto. And I think on the U.S. launch, we're off to a good start and getting again the key elements in place to really drive this launch. As a reminder, the population is metastatic CRPC patients who are post relevant chemotherapies.

使用 Pluvicto 轉到下一張幻燈片。所以我們在 - 在本季度末，我收到了 Pluvicto 的批准。而且我認為在美國的發射中，我們有了一個良好的開端，並再次獲得了真正推動這次發射的關鍵要素。提醒一下，人群是相關化療後的轉移性 CRPC 患者。

Patient selection is driven by a Gallium PSMA-11 agent to identify patients who would benefit from Pluvicto. There was a 38% reduction in the risk of death in these patients. So a lot of physician and KOL interest in the medicine in the prostate cancer space. 6 infusions, 6 -- 6 week -- over 6 weeks, which really gives the opportunity for a onetime therapy over that period of time and then patients derive the benefit.

患者選擇由鎵 PSMA-11 試劑驅動，以確定將從 Pluvicto 中受益的患者。這些患者的死亡風險降低了 38%。因此，很多醫生和 KOL 都對前列腺癌領域的藥物感興趣。 6 次輸注，6 - 6 週 - 超過 6 週，這確實提供了在這段時間內進行一次性治療的機會，然後患者從中受益。

We're building on our Lutathera experience with this medicine. Our commercial field teams are in place. We see high awareness already in the 240 treatment centers that we're targeting initially. 40 RLT centers are already onboarded into the ordering system and many of these centers have experience with us. And we've submitted the application for the permanent A-code for this medicine.

我們正在利用這種藥物的 Lutathera 經驗。我們的商業現場團隊已經到位。我們在最初瞄準的 240 個治療中心中已經看到了很高的認識。 40 個 RLT 中心已加入訂購系統，其中許多中心都有我們的經驗。我們已經提交了該藥永久 A 代碼的申請。

Now in Europe, we expect approval in the second half of '22. And we also are progressing on track with our Phase III studies in the pre-taxane and hormone sensitive setting and we're also -- which would expand the patient population 3 to 4x and allow us to target a patient population to enable this to be a multibillion-dollar brand over time. And we're evaluating additional Phase III studies in the earlier-line setting.

現在在歐洲，我們預計在 22 年下半年獲得批准。我們也正在推進我們在紫杉烷前和激素敏感環境中的 III 期研究，我們也在——這將使患者群體擴大 3 到 4 倍，並允許我們針對患者群體，使其成為隨著時間的推移，一個價值數十億美元的品牌。我們正在評估早期階段的其他 III 期研究。

Now moving to the next slide. Wanted to say a word on Sandoz. Our business dynamics in Sandoz, as you saw, in the quarter have really stabilized. We are benefiting from a lower prior year comparison. Nonetheless, it is a positive time to see now stabilizing Sandoz business, with good growth, 8% overall. It was driven by performance in Europe at 9%. So we do see now moving towards the bottoming out of the U.S. business as we look to get that region back to growth. Very good biopharma performance and retail performance. Core operating income was up quite significantly, but again benefiting from both prior year comps as well as certain one-timers.

現在轉到下一張幻燈片。想對山德士說一句話。如您所見，本季度我們在 Sandoz 的業務動態已經真正穩定下來。我們受益於較低的上一年比較。儘管如此，現在是看到山德士業務穩定的好時機，總體增長 8% 的良好增長。它是由歐洲 9% 的業績推動的。因此，我們確實看到美國業務正在觸底反彈，因為我們希望該地區恢復增長。非常好的生物製藥業績和零售業績。核心營業收入大幅增長，但再次受益於上一年的業績和某些一次性收入。

And so overall, given the geographical uncertainties, price erosion and other inflationary pressure in Sandoz spaces, we're maintaining our guidance for Sandoz on the full year, but we'll, of course, continue to monitor to see how Sandoz performs.

因此，總體而言，鑑於山德士空間的地理不確定性、價格侵蝕和其他通脹壓力，我們將維持對山德士全年的指導，但我們當然會繼續監測山德士的表現。

Just as a reminder, we continue to view Sandoz as having the potential to be the leading generics company in the world driven by its biosimilars' presence and strength as well as key success factors which we reviewed on the previous call. Overall, our strategic review remains on track, and we would plan to provide an update on the strategic review at the latest by the end of this year.

提醒一下，我們繼續認為山德士有潛力成為世界領先的仿製藥公司，這得益於其生物仿製藥的存在和實力以及我們在上次電話會議上審查的關鍵成功因素。總體而言，我們的戰略審查仍在進行中，我們計劃最遲在今年年底之前提供戰略審查的最新信息。

So moving to the next slide. In terms of the pipeline, some important milestones, but I'll really dive in on just a handful.

所以轉到下一張幻燈片。就管道而言，一些重要的里程碑，但我真的會深入探討其中的一小部分。

Pluvicto was our key approval in the quarter that we had some other approvals around the world, as you can see here. In terms of submissions, we are continuing to move forward with Tislelizumab in the EU and our filing is on track in the U.S. as well.

正如您在此處看到的，Pluvicto 是我們在本季度獲得的主要批准，我們在全球範圍內獲得了其他一些批准。在提交方面，我們正在繼續推進在歐盟的替雷利珠單抗，我們的提交也在美國進行。

I'll go through in a little bit more detail, our JDQ data on the subsequent slide.

我將在下一張幻燈片中更詳細地介紹我們的 JDQ 數據。

We continue to see good interest in Iptacopan around the world as we head towards our first Phase III readout in the second half of this year and we're on track. We've already started our T-Charge Phase II study in multiple myeloma and plan to start in Phase III in DLBCL in the second half of the year. And I've already mentioned the Phase III start of Zolgensma.

我們繼續看到世界各地對 Iptacopan 的濃厚興趣，因為我們將在今年下半年進行第一次 III 期讀數，並且我們正在走上正軌。我們已經開始了針對多發性骨髓瘤的 T-Charge II 期研究，併計劃在下半年開始在 DLBCL 的 III 期研究。我已經提到了 Zolgensma 的第三階段開始。

So let's move for a moment to JDQ. So at AACR, on the next slide, so we showed early signs of clinical activity with acceptable safety and tolerability for this KRAS G12C. As a reminder, have a unique structure to this medicine versus the other G12C inhibitors which we believe allows us to optimize the PK/PD for the medicine.

因此，讓我們先看看 JDQ。所以在 AACR，在下一張幻燈片上，我們展示了這種 KRAS G12C 具有可接受的安全性和耐受性的臨床活動的早期跡象。提醒一下，這種藥物與其他 G12C 抑製劑相比具有獨特的結構，我們認為這使我們能夠優化藥物的 PK/PD。

When you look at the data set, we demonstrated a competitive safety and efficacy profile, though, again, with a caveat that this is a small study, 57% ORR at the target dose of 200 milligrams BID. No grade 3 or higher treatment-related AEs, so really nice safety profile.

當您查看數據集時，我們展示了具有競爭力的安全性和有效性概況，不過，再次需要注意的是，這是一項小型研究，目標劑量為 200 毫克 BID 時的 ORR 為 57%。沒有 3 級或更高級別的治療相關 AE，因此安全性非常好。

When we look at the modeling of the overall PK of this medicine, high systemic exposure, high target level occupancy. So we're pleased with how the medicine has performed thus far.

當我們查看該藥物的整體 PK 建模時，高全身暴露，高目標水平佔用。因此，我們對該藥物迄今為止的表現感到滿意。

So we're moving forward rapidly in recruiting our combination study with SHP2 as well as another separate study with anti-PD-1. And so both the studies are moving forward. And we're also preparing to start our monotherapy Phase III program in small cell lung cancer versus chemotherapy which we plan to open shortly.

因此，我們正在快速推進我們與 SHP2 的聯合研究以及另一項與抗 PD-1 的單獨研究。因此，這兩項研究都在向前推進。我們還準備在小細胞肺癌與化療方面啟動我們的單藥治療 III 期項目，我們計劃很快啟動該項目。

Now moving to the next slide. We also wanted to provide an update on NATALEE. So based on our regular update of the number of events that we are accruing, we now forecast the trial to complete in 2023 as the current event rate is lower than our originally forecasted event rate for the study. This is a regular process we go through. And now when we look at these forecast versus -- or look at our actuals versus our forecast, we're currently predicting a 2023 completion of the study.

現在轉到下一張幻燈片。我們還想提供有關 NATALEE 的最新信息。因此，根據我們對我們累積的事件數量的定期更新，我們現在預測試驗將在 2023 年完成，因為當前的事件發生率低於我們最初預測的研究事件發生率。這是我們經歷的一個常規過程。現在，當我們查看這些預測與 - 或查看我們的實際值與我們的預測時，我們目前預測該研究將在 2023 年完成。

On the left-hand side, you see the study design remains unchanged from our previous update, 5,000 patients randomized 1:1 to ribociclib plus estrogen therapy versus estrogen therapy alone. Patients receive Kisqali 400 milligrams per day for 36 months. So a longer treatment duration, a lower dose than the metastatic setting to really try to ensure we keep patients on therapy and keep them on therapy longer to drive the efficacy signal.

在左側，您會看到研究設計與我們之前的更新保持不變，5,000 名患者按 1:1 隨機分配接受 ribociclib 加雌激素治療與單獨使用雌激素治療。患者每天接受 Kisqali 400 毫克，持續 36 個月。因此，更長的治療持續時間，比轉移性設置更低的劑量，以真正嘗試確保我們讓患者繼續接受治療，並讓他們接受更長時間的治療，以驅動療效信號。

So in terms of the recruitment, we completed 5,000 patients in April 2021. Our primary analysis is that 500 events. We have 3 -- approximately 300 events to date. In the quarter, we successfully completed a futility analysis. We have 2 interim analyses planned between now and the end of the study, but neither has occurred yet. And the discontinuation rate remains low in the single-digit percentages, which I think demonstrates the overall profile in terms of safety and tolerability of the medicine.

因此，在招募方面，我們在 2021 年 4 月完成了 5,000 名患者。我們的主要分析是這 500 起事件。迄今為止，我們有 3 - 大約 300 個事件。在本季度，我們成功完成了一項無用分析。從現在到研究結束，我們計劃進行 2 次中期分析，但都沒有發生。而且停藥率在個位數百分比中仍然很低，我認為這表明了藥物在安全性和耐受性方面的總體情況。

So all on track. We'll continue to keep you updated as we progress this important study. As a reminder, the opportunity here is significant. We estimate in 2027 that the market for -- in the adjuvant setting could be $7 billion. And the ability to target both the intermediate and the severe patients is significant in that we estimate there are 3x as many patients in the intermediate risk versus the high-risk patient population. So this would offer us, if successful, a significant medicine for the company.

所以一切都在軌道上。隨著這項重要研究的進展，我們將繼續為您提供最新信息。提醒一下，這裡的機會很重要。我們估計，到 2027 年，輔助治療的市場規模可能達到 70 億美元。同時針對中度和重度患者的能力意義重大，因為我們估計中度風險患者的數量是高風險患者群體的 3 倍。因此，如果成功的話，這將為我們提供對公司而言重要的藥物。

Moving to the next slide. So our overall events are on track. I won't go through the slide in detail. We'll continue to keep you updated as we progress on these events across our regulatory decision, submission, study readouts and study starts.

轉到下一張幻燈片。所以我們的整體活動都在進行中。我不會詳細介紹幻燈片。隨著我們在監管決策、提交、研究讀數和研究開始等方面取得進展，我們將繼續為您提供最新信息。

So moving to the next slide. With that, I'll hand the mic over to Harry. Harry?

所以轉到下一張幻燈片。有了這個，我會把麥克風交給哈利。哈利？

Yes. Thank you, Vas. Good morning, good afternoon, everyone. I'm now going to walk you through some of the financials of the first quarter. And as always, my comments refer to growth rates in constant currencies unless otherwise noted.

是的。謝謝你，瓦斯。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。和往常一樣，除非另有說明，否則我的評論指的是固定貨幣的增長率。

So on the next slide, we present our results for the quarter. Overall, as Vas mentioned, we delivered solid sales and profit growth. I think it's also important to keep in mind that this quarter's results with prior year comparisons are affected by the divestment of our Roche investment and the corresponding loss of income from associated companies, which you see here in the lines below operating income.

因此，在下一張幻燈片中，我們展示了本季度的業績。總體而言，正如 Vas 所說，我們實現了穩健的銷售和利潤增長。我認為同樣重要的是要記住，本季度的業績與上一年的比較受到我們羅氏投資的撤資和關聯公司的相應收入損失的影響，您可以在營業收入下方的行中看到這些損失。

To aid the comparisons, we have published a reconciliation of our 2021 results excluding those impacts on our website, and we have also shown here the growth excluding prior year Roche investment income.

為了幫助進行比較，我們發布了不包括對我們網站的影響的 2021 年業績的對賬，我們還在此處顯示了不包括上一年羅氏投資收入的增長。

In quarter 1, sales and core operating income grew 5% and 9%, respectively, now with the sales benefiting from the strong performance of our in-market brands and core operating income driven by higher sales and increased productivity.

在第一季度，銷售額和核心營業收入分別增長了 5% 和 9%，現在銷售額受益於我們在市場品牌的強勁表現，而核心營業收入則得益於更高的銷售額和生產力的提高。

Net income grew 15%, mainly driven by higher core operating income.

淨收入增長 15%，主要受核心營業收入增加的推動。

And core EPS grew 2%. However, as you can see, if we exclude the impact of the prior year Roche income, net income would have grown 32% and core EPS 12%. Of course, we expect these impacts on EPS and core EPS to be offset over time by our ongoing $15 billion share buyback program which we expect to conclude in the second half of 2023.

核心每股收益增長 2%。但是，如您所見，如果我們排除上一年羅氏收入的影響，淨收入將增長 32%，核心每股收益將增長 12%。當然，我們預計這些對每股收益和核心每股收益的影響將隨著時間的推移被我們正在進行的 150 億美元股票回購計劃所抵消，我們預計該計劃將在 2023 年下半年完成。

Free cash flow was negatively impacted by $0.5 billion due to the loss of gross annual dividend share paid out last year in March. However, important to note, underlying free cash flow is in line with expectations. And operationally, we are on track to reach our full year free cash flow objectives.

由於去年 3 月支付的年度股息總額減少，自由現金流受到了 5 億美元的負面影響。然而，值得注意的是，潛在的自由現金流符合預期。在運營方面，我們有望實現全年自由現金流目標。

In summary, it has been a solid start to the year with the strength of our in-market growth drivers, (inaudible) Entresto, Kesimpta, Cosentyx, Zolgensma and Kisqali and our new launches, including Leqvio and Pluvicto, reinforcing our confidence in our midterm growth expectations.

總而言之，憑藉我們的市場增長驅動力（聽不清）Entresto、Kesimpta、Cosentyx、Zolgensma 和 Kisqali 以及我們的新產品（包括 Leqvio 和 Pluvicto）的實力，今年是一個堅實的開端，增強了我們對我們的信心中期增長預期。

As you can see on the next slide, Innovative Medicines sales grew 4%, benefiting from the strong performance of the in-market brands, partly offset by generic erosion, especially in the Oncology portfolio.

正如您在下一張幻燈片中看到的那樣，創新藥物的銷售額增長了 4%，這得益於市場內品牌的強勁表現，部分被仿製藥侵蝕所抵消，尤其是在腫瘤學產品組合中。

Innovative Medicines bottom line grew 5% and core margin reached 35.9%, up slightly from the prior year in constant currencies.

創新藥物利潤增長 5%，核心利潤率達到 35.9%，按固定匯率計算，較上年略有上升。

Sandoz numbers benefited this year due to a significantly lower prior year base with business dynamics continuing to return to normal with net sales up 8% and core operating income up 20%. And the margin is improving 330 basis points to 22.8% of sales. Overall, the group core margin increased by 111 basis points to 32.6% mainly driven by Sandoz' performance for the quarter.

今年山德士的數據受益，因為上一年的基數顯著降低，業務動態繼續恢復正常，淨銷售額增長 8%，核心營業收入增長 20%。利潤率提高了 330 個基點，達到銷售額的 22.8%。總體而言，集團核心利潤率增長 111 個基點至 32.6%，主要受山德士本季度業績的推動。

Turning now to our guidance slide on Slide 24. We are confirming our guidance for the full year. And as a reminder, within the divisions, we expect another year of Innovative Medicines sales growing mid-single digit and core operating income to grow mids- to high-single digit ahead of sales.

現在轉到幻燈片 24 上的指導幻燈片。我們正在確認全年的指導。提醒一下，在各部門內，我們預計創新藥物銷售額將再增長中個位數，核心營業收入將超過銷售額增長中個位數至高個位數。

The expected Innovative Medicines core margin increase will be driven by good top line momentum and continuation of productivity programs, including the recently announced new organizational structure. These drivers are expected to more than offset the anticipated higher energy cost and inflation pressures in our supply chain.

預期的創新藥物核心利潤率增長將受到良好的頂線勢頭和生產力計劃的持續推動，包括最近宣布的新組織結構。預計這些驅動因素將抵消我們供應鏈中預期的更高能源成本和通脹壓力。

And for Sandoz, it's important to note that the very low quarter 1 prior year base with a weak cough and cold season to COVID and the uncertainty related to currency political -- current geopolitical events.

對於 Sandoz 來說，重要的是要注意，前一年第一季度的基數非常低，COVID 的咳嗽和感冒季節很弱，以及與貨幣政治相關的不確定性——當前的地緣政治事件。

Therefore, we continue to expect the top line to be broadly in line with the prior year and core operating income to decline low to mid-single digit. Of course, we will be monitoring during quarter 2 and given the strong quarter 1 performance to see if we can give an update here.

因此，我們繼續預計收入將與上年基本持平，核心營業收入將下降到中個位數。當然，我們將在第 2 季度進行監控，並鑑於第 1 季度的強勁表現，看看我們是否可以在此處提供更新。

But for now, given that the geopolitical events are likely to hit a bit harder Sandoz, if you will, we remain cautious here. This will be mainly driven by the expected gross margin pressures because also pricing and inflation coming in. And of course, we will have got a clearer picture later in the year.

但就目前而言，鑑於地緣政治事件可能會對 Sandoz 造成更大的打擊，如果你願意的話，我們在這裡保持謹慎。這將主要受到預期的毛利率壓力以及定價和通脹的影響。當然，我們將在今年晚些時候獲得更清晰的畫面。

For the group, we expect both the top and the bottom line to grow mid-single digit. The key assumption for this guidance is that we see continued return to normal global health care systems, including prescribing dynamics and that no Sandoz LAR generics enter in the U.S. in 2022.

對於該集團，我們預計頂線和底線都將增長中個位數。該指南的關鍵假設是，我們看到全球醫療保健系統繼續恢復正常，包括處方動態，並且 2022 年沒有山德士 LAR 仿製藥進入美國。

And then finally, on Slide 25, given the strengthening U.S. dollar and as currencies are constantly changing, I want to bring to your attention the estimated currency impact on our results using current exchange rates.

最後，在幻燈片 25 上，鑑於美元走強以及貨幣不斷變化，我想提請您注意使用當前匯率估算的貨幣對我們業績的影響。

In quarter 1, currency had a negative 4% point impact on net sales and a negative 6% point impact on core operating income. Looking forward, if late April rates prevail for the remainder of '22, we expect the full year impact of currencies on top line to be a negative 4% points and on bottom line a negative 5% points. In quarter 2, the impact on sales would be negative 5% to negative 6% points and on bottom line negative 6% points. And as a reminder, we update these currency impact estimates monthly on our website.

在第一季度，貨幣對淨銷售額產生了 4% 的負面影響，對核心營業收入產生了 6% 的負面影響。展望未來，如果 4 月下旬的利率在 22 年剩餘時間內占主導地位，我們預計全年貨幣對頂線的影響為負 4%，對底線的影響為負 5%。在第 2 季度，對銷售的影響將是負 5% 到負 6%，對底線的影響是負 6%。提醒一下，我們每月都會在我們的網站上更新這些貨幣影響估計值。

And with that, I hand it back to Vas.

有了這個，我把它交還給 Vas。

Thank you, Harry. So if we go to Slide 27. Also today, we announced the appointment of Ronny Gal as our Chief Strategy and Growth Officer. As a reminder, we created the strategy and growth function to enable us to combine corporate strategy, R&D portfolio management and external business development into a single unit to help us drive the near, mid- and long-term growth of the company. So Ronny will report to me as he sits on the executive committee. He brings over 20 years of life sciences experience, both on the analytical side of things, but also deep understanding of the science in the U.S. commercial environment. Previously worked at management consulting as well as business development. So very excited to welcome Ronny to the team no later than August 1 of this year.

謝謝你，哈利。因此，如果我們轉到幻燈片 27。同樣在今天，我們宣布任命 Ronny Gal 為我們的首席戰略和增長官。提醒一下，我們創建了戰略和增長功能，使我們能夠將企業戰略、研發組合管理和外部業務發展結合到一個單元中，以幫助我們推動公司的近期、中期和長期增長。因此，Ronny 將在擔任執行委員會成員時向我匯報。他帶來了 20 多年的生命科學經驗，無論是在事物的分析方面，還是對美國商業環境中的科學的深刻理解。此前曾在管理諮詢和業務發展部門工作。非常高興能在今年 8 月 1 日之前歡迎 Ronny 加入團隊。

So moving to the last slide, 6 key priorities we outlined in January, and they remain on track, successfully launching our key -- driving our key launches Leqvio, Kesimpta, Pluvicto and Scemblix; maintaining the growth momentum across our 6 key growth drivers; progressing our pipeline of over 20 potential significant assets that had the potential to be approved by 2026; optimizing our portfolio with our Sandoz review on track but also remaining disciplined on M&A and business development; delivering returns, and so the recent reorganization with a potential of $1 billion plus productivity that we're committing to has been announced, and we'll continue to work through that over the course of this year; and of course, maintaining the foundations of culture, data science and ESG.

所以轉到最後一張幻燈片，我們在 1 月份概述的 6 個關鍵優先事項，它們仍然在軌道上，成功啟動了我們的關鍵——推動我們的關鍵發布 Leqvio、Kesimpta、Pluvicto 和 Scemblix；保持我們 6 個主要增長動力的增長勢頭；推進我們有可能在 2026 年之前獲得批准的 20 多項潛在重大資產的管道；優化我們的投資組合，讓我們的 Sandoz 審查步入正軌，但同時在併購和業務發展方面保持自律；提供回報，因此最近宣布了我們承諾的 10 億美元和生產力的重組，我們將在今年繼續努力；當然，還要維護文化、數據科學和 ESG 的基礎。

So with that, I'll close and open the line for questions. Operator? (Operator Instructions)

因此，我將關閉並打開問題線。操作員？ （操作員說明）

(Operator Instructions)

（操作員說明）

Sorry, one note I forgot to mention. Please limit yourself to one question and we'll try to do multiple rounds if we have time. Thank you.

對不起，我忘了提到一個註釋。請把自己限制在一個問題上，如果有時間，我們會嘗試做多輪。謝謝你。

(Operator Instructions) Your first question today comes from the line of Graham Parry from Bank of America.

（操作員說明）您今天的第一個問題來自美國銀行的 Graham Parry。

So it's a follow-up on NATALEE. The original trial design, I think, only had 2 interim. So 1 was a futility at 40% of events. And then there was a stop for outstanding efficacy at 70% of events. And I think the total event number you're looking for there was just over 300.

所以這是對 NATALEE 的跟進。我認為最初的試驗設計只有 2 個中間階段。所以 1 在 40% 的事件中是無用的。然後在 70% 的事件中停止了出色的療效。而且我認為您正在尋找的總事件數剛剛超過 300。

But you're highlighting now that you have 2 efficacy interims as well as the futility that's already passed. So can you just help us understand the trial design. So what percentage of events was that futility analysis performed at? And then at what percentage of events are the 2 upcoming efficacy analyses? And just to confirm, those have the potential with the stop for efficacy in them.

但是您現在要強調的是，您有 2 個臨時效力以及已經過去的無效。所以你能不能幫助我們理解試驗設計。那麼，無效性分析執行的事件百分比是多少？然後，即將進行的 2 項療效分析佔事件的百分比是多少？並且只是為了確認，那些有可能停止它們的功效。

Yes. Thanks, Graham. So as you know, we amended the study protocol that increased to 500 events along the way. And with that, we added -- we updated as well the various readouts.

是的。謝謝，格雷厄姆。如您所知，我們修改了研究方案，沿途增加了 500 個事件。有了這個，我們添加了 - 我們還更新了各種讀數。

So the -- I don't have in front of me the readout for the futility endpoint. But I can say that our interim analyses for efficacy are at the 70% and 85% information fractions. So that's when we would expect to have those interim analyses. But of course, it's difficult to predict based on an event-driven study as to when exactly those would occur. And so we'll continue to keep you up to date. And as a reminder, we don't guide to specific time lines on interim analyses, and we'll only provide updates if material information is provided by the DMC. Next question operator.

所以——我面前沒有無效端點的讀數。但我可以說，我們對療效的中期分析是在 70% 和 85% 的信息部分。所以這就是我們期望進行這些中期分析的時候。但是，當然，很難根據事件驅動的研究來預測這些事件何時會發生。因此，我們將繼續為您提供最新信息。提醒一下，我們不會針對中期分析指定具體的時間線，並且我們只會在 DMC 提供重要信息的情況下提供更新。下一個問題運算符。

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。

It's a broader question on multiple sclerosis. It was flagged up on a call yesterday that traditionally Russia and Ukraine is disproportionately involved in MS studies. Since you have, I think, about 30 ongoing MS trials around the order, I just wonder if you could give us an update on the current situation, any potential exposure you have [two] trials in Russia and Ukraine and any effect that could have on trial time lines.

這是關於多發性硬化症的更廣泛的問題。昨天在電話會議上指出，傳統上俄羅斯和烏克蘭不成比例地參與 MS 研究。我認為，由於您在訂單周圍進行了大約 30 次正在進行的 MS 試驗，我只是想知道您是否可以向我們提供有關當前情況的最新信息，您在俄羅斯和烏克蘭進行的 [2] 試驗的任何潛在風險以及可能產生的任何影響在審判時間線上。

Yes. Thanks, Simon. So overall, again, we feel like our trials are manageable in Russia -- in Russia and the Ukraine. We are in the single-digit percentages in terms of the percentage of Russia and Ukraine patients in our -- in our global studies.

是的。謝謝，西蒙。所以總的來說，我們覺得我們的試驗在俄羅斯是可控的——在俄羅斯和烏克蘭。在我們的全球研究中，就俄羅斯和烏克蘭患者的百分比而言，我們處於個位數的百分比。

Now specifically in multiple sclerosis, we're in the roughly low to mid-teens on the studies in terms of the percent of the global patients for our BTK inhibitor multiple sclerosis studies, but we already have plans in place to offset those. And so at the moment, we believe we can fully mitigate the patients required from those 2 countries.

現在特別是在多發性硬化症方面，就我們的 BTK 抑製劑多發性硬化症研究的全球患者百分比而言，我們的研究大約處於低至十幾歲，但我們已經制定了抵消這些的計劃。因此，目前，我們相信我們可以完全減輕這兩個國家所需的患者數量。

No patients in our multiple sclerosis BTK study or LOU studies were -- have been enrolled so far. And so we'll simply reallocate to other markets and we expect to remain on track. We'll, of course, keep you updated if anything were to change in that regard. Next question operator.

到目前為止，我們的多發性硬化症 BTK 研究或 LOU 研究中沒有患者被招募。因此，我們將簡單地重新分配到其他市場，我們預計將保持在正軌上。當然，如果這方面有任何變化，我們會及時通知您。下一個問題運算符。

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。

It's another Russian question, one for Harry, please. The annual report for last year shows that you have just under $0.5 billion of Russian ruble receivables. I'd be interested to understand, how is cash collection today? Are you limiting deliveries to only people who pay you upfront? And then how should we think about impairment testing on that quite sizable amount of money? And then finally, Harry, if you were to have to write some down, would it go through core? Or would it not?

這是另一個俄羅斯問題，請給哈利。去年的年度報告顯示，俄羅斯盧布的應收賬款不到 5 億美元。我很想知道，今天的現金收款怎麼樣？您是否將交付僅限於預先付款的人？那麼我們應該如何考慮對這麼大筆資金進行減值測試呢？最後，哈利，如果你必須寫下一些，它會通過核心嗎？或者不會？

Thanks, Matthew. Harry?

謝謝，馬修。哈利？

Yes. So Matthew, overall, our cash collections and shipments actually are very normal. Cash collections are very good, actually. Now over the past years and, in this role, almost over 9 years, we always had here or there some difficulties with the wholesaler and then we put these wholesaler in the question on a payment plan or potentially prepayment plan. But that's not the case yet with any of them. Of course, we monitor on a daily basis. And the receivables are in ruble. You have seen also ruble returning back, if you were, to strength, and we have not seen difficulties to pay.

是的。所以馬修，總的來說，我們的現金收款和發貨其實很正常。實際上，現金收款非常好。現在在過去的幾年裡，在這個職位上，差不多 9 年多，我們總是在這里或那裡與批發商有一些困難，然後我們把這些批發商放在付款計劃或潛在的預付款計劃的問題上。但他們中的任何一個都不是這種情況。當然，我們每天都會進行監控。應收賬款是盧布。你也看到盧布恢復了實力，如果你是的話，我們還沒有看到支付困難。

Now in terms of impairments, we would have to see, but I don't expect actually impairments on it. We are highly insured. A significant part of these are insured. And from that standpoint, we carefully monitor. We are insured and we don't see issues yet. Again, we monitor should that change, we would inform you. But I see a very stable product flow and a very stable cash collection.

現在就損害而言，我們將不得不看到，但我不認為它實際上會受到損害。我們是高度保險的。其中很大一部分已投保。從這個角度來看，我們會仔細監控。我們有保險，我們還沒有看到問題。同樣，如果發生這種變化，我們會進行監控，我們會通知您。但我看到了非常穩定的產品流和非常穩定的現金回收。

Thanks, Harry. And just one update to Graham's first question. The futility analysis was done at a 40% information fraction. I would also note, it does take us a couple of months between a lot for one of these to actually have the DMC read the data. So next question operator.

謝謝，哈利。格雷厄姆的第一個問題只是一個更新。無用性分析是在 40% 的信息分數下進行的。我還要注意，其中一個確實需要幾個月的時間才能真正讓 DMC 讀取數據。所以下一個問題運算符。

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。

So can I just please ask about Kesimpta life cycle management. So I appreciate you're still early -- in the early stages for the products. But one of your key competitors has started a 6-month subcu trial earlier this year and they also have a high-dose trial ongoing. So do you have any plans to extend the dosing frequency and/or change the dose for Kesimpta in an attempt to really ensure durable share gains? I appreciate it's a bit further down the line, but just curious to hear your thoughts.

那麼我能否請教一下 Kesimpta 生命週期管理。所以我很感激你還早——在產品的早期階段。但是你的一個主要競爭對手今年早些時候已經開始了為期 6 個月的 subcu 試驗，他們也正在進行大劑量試驗。那麼，您是否有任何計劃延長 Kesimpta 的給藥頻率和/或改變劑量，以真正確保持久的份額收益？我很欣賞它有點進一步，但只是想听聽你的想法。

Yes. Thanks, Wimal. So first, I think the key benefit of Kesimpta is that the patient doesn't have to go into the center and have to deal with pretreatment with steroids and additional observation. So our understanding of competitor life cycle management activities would still involve the patient ultimately coming in to the center and of course then going into the various elements involved with that. So our focus remains on providing that flexibility for patients. We find it to be a key value driver, both to outstanding safety, excellent efficacy, but also monthly at-home administration. In terms of total time in the patient's lives, it's significantly, significantly lower.

是的。謝謝，維馬爾。所以首先，我認為 Kesimpta 的主要好處是患者不必進入中心，不必處理類固醇的預處理和額外的觀察。因此，我們對競爭對手生命週期管理活動的理解仍將涉及患者最終進入中心，然後當然會進入與之相關的各種要素。因此，我們的重點仍然是為患者提供這種靈活性。我們發現它是一個關鍵的價值驅動因素，無論是卓越的安全性、卓越的功效，還是每月在家管理。就患者生命中的總時間而言，它明顯非常低。

We are evaluating various life cycle management activities. But at this point in time, we haven't actually instigated, I guess, any new studies. We'll continue to evaluate, and we'll keep you posted. Next, operator? -- Question operator?

我們正在評估各種生命週期管理活動。但在這個時間點上，我猜我們實際上還沒有發起任何新的研究。我們將繼續評估，我們會及時通知您。接下來，運營商？ -- 提問操作員？

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

您的下一個問題來自花旗銀行的 Andrew Baum。

Unusually, across the industry, Novartis has built and is building a large cardiovascular presence. I'm just curious whether you see any role for a Factor XI inhibitor within that space. There's at least a couple of partnered agents (inaudible), Abelacimab which I can barely pronounce but you're familiar with given it came from your own portfolio?

不同尋常的是，在整個行業中，諾華已經建立並正在建立龐大的心血管業務。我只是好奇您是否看到因子 XI 抑製劑在該領域中的任何作用。至少有幾個合作代理（聽不清），Abelacimab，我幾乎不能發音，但你很熟悉，因為它來自你自己的投資組合？

And then second, potentially partnering with Bayer on the Factor XI. I wonder if you had any comments.

其次，可能與拜耳在 Factor XI 上合作。我想知道你是否有任何意見。

Yes. Thanks, Andrew. So in terms of Factor XI, we developed a very attractive Factor XI agent that we ultimately determined at the end of Phase II that it would be better to move forward in other people's hands. So we struck a partnership with Blackstone Life Sciences. They have taken the medicine forward and continue to develop it.

是的。謝謝，安德魯。因此，就因子 XI 而言，我們開發了一種非常有吸引力的因子 XI 代理，我們最終在第二階段結束時確定，在其他人手中前進會更好。因此，我們與 Blackstone Life Sciences 建立了合作夥伴關係。他們已經將藥物向前推進並繼續開發。

So we continue to monitor the progress of the medicine. At the moment, our view is that the focus we have on heart failure and on the various contributors to ASCVD between, of course, PCSK9, Lp(a) as well as other factors, is enough at the moment to take on. But we certainly are monitoring the space with a keen eye to what is the size of studies and the amount of investment that will be required to differentiate on safety given that NOACs will ultimately go generic in the coming years and that will be the standard that we'd have to go up against. But we'll keep you posted if anything were to change. Next question operator.

所以我們繼續監測藥物的進展。目前，我們的觀點是，我們關注心力衰竭和導致 ASCVD 的各種因素，當然，PCSK9、Lp(a) 以及其他因素，目前足以承擔。但是，鑑於 NOAC 最終將在未來幾年通用化，而這將成為我們的標準，我們當然會密切關注研究的規模以及在安全性方面差異化所需的投資金額。 'd不得不去反對。但如果有任何變化，我們會及時通知您。下一個問題運算符。

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 looking at the oncology franchise in general, there seems to be a number of destockings in Q1. So should we anticipate this to reverse in Q2? And also, should we think for the rest of the year about an acceleration as diagnosis improves as we come out of the pandemic? Just thoughts on the overall franchise there.

僅從總體上看腫瘤學專營權，第一季度似乎有一些去庫存。那麼我們是否應該預計這種情況會在第二季度逆轉？而且，我們是否應該在今年餘下的時間裡考慮隨著我們擺脫大流行病而改善診斷的加速？只是對那裡的整體特許經營權的想法。

Yes. Thanks, Richard. In quarter 1, we saw a few dynamics. One, we continue to see in certain cancers that we have a focus, in such as breast cancer, lower diagnosis rates than pre-COVID levels and lower NBRx, as I mentioned, with Kisqali. That combined is we also did see destocking and impacts on some of our, let's call it, more mature brands or mature promoted brands as well as off-patent brands.

是的。謝謝，理查德。在第一季度，我們看到了一些動態。第一，正如我所提到的，Kisqali 繼續在某些癌症中看到我們關注的某些癌症，例如乳腺癌，其診斷率低於 COVID 之前的水平和 NBRx。綜合起來，我們也確實看到了去庫存化和對我們的一些（我們稱之為）更成熟的品牌或成熟的推廣品牌以及非專利品牌的影響。

At the moment, we do expect the trend to stabilize and we expect in the remainder of the year the performance in Oncology to be driven by our newer medicines, of course, Kisqali as well as Pluvicto, Scemblix, et cetera. But of course, continued performance from Promacta/Revolade and Jakavi. And so I think we'll have to monitor it closely, but we're optimistic that things will start to get back to normal over the course of Q2. Next question operator.

目前，我們確實預計這一趨勢會穩定下來，我們預計今年剩餘時間腫瘤學的表現將由我們的新藥推動，當然還有 Kisqali 以及 Pluvicto、Scemblix 等。但當然，Promacta/Revolade 和 Jakavi 的持續表現。所以我認為我們必須密切關注它，但我們樂觀地認為事情將在第二季度開始恢復正常。下一個問題運算符。

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。

Perhaps one on JDQ. Congratulations on the impressive AACR update. Just curious in your strategy to differentiate or catch up there given you're a little late behind the two leaders in that space. I'm particularly interested on the latest perspective as regard to the SHP2 combination. I see you started an internal combination program. Does that signal deprioritization of the Mirati collaboration and when indeed might be seen update of -- clinical update of the combination days from either Mirati study or indeed your own internal efforts?

也許在 JDQ 上一個。祝賀令人印象深刻的 AACR 更新。只是好奇你的策略來區分或趕上那裡，因為你在那個領域落後於兩位領導者有點晚了。我對有關 SHP2 組合的最新觀點特別感興趣。我看到你開始了一個內部組合計劃。這是否表明 Mirati 合作的優先級被取消，以及何時可以看到 Mirati 研究或您自己內部努力的組合天的臨床更新？

Thanks, Emmanuel. One of the things we've observed thus far in very early clinical data is in order to have a good combination agent, we need a pretty clean profile from the G12C agents. So one of the advantages we hope we will have, is given the absence of Grade 3/4 AEs in our studies, but it is a kind of combination agent of choice so that despite us being late we would have the opportunity to combine the medicine with other attractive agents.

謝謝，伊曼紐爾。到目前為止，我們在非常早期的臨床數據中觀察到的一件事是，為了獲得良好的組合藥物，我們需要 G12C 藥物的非常乾淨的概況。因此，我們希望我們擁有的優勢之一是，鑑於我們的研究中沒有 3/4 級 AE，但它是一種選擇的聯合藥物，因此儘管我們遲到了，但我們仍有機會聯合藥物與其他有吸引力的代理商。

With our SHP2, I think that's part of the story. We do have studies ongoing with Mirati and Amgen, but we believe our JDQ molecule is optimized for combination with our SHP2 to really allow us to get to the optimal dosing with limited AEs and hopefully maximize the benefit for patients in our studies.

對於我們的 SHP2，我認為這是故事的一部分。我們確實正在進行與 Mirati 和 Amgen 的研究，但我們相信我們的 JDQ 分子已針對與我們的 SHP2 組合進行了優化，從而真正使我們能夠以有限的 AE 獲得最佳劑量，並希望在我們的研究中最大限度地為患者帶來益處。

So the key to our strategy is having a medicine that can be the combination agent of choice from a G12C standpoint and then hopefully demonstrate, despite us being late in mono, that we'll be able to win the battle in the long run with combinations, PD-1, SHP2 and perhaps others.

因此，我們戰略的關鍵是擁有一種從 G12C 角度來看可以作為首選組合藥物的藥物，然後希望證明，儘管我們在單藥方面遲到了，但從長遠來看，我們將能夠通過組合贏得這場戰鬥, PD-1, SHP2 或許還有其他。

Important to note, we still need to do larger studies. I don't want us to overextend our interpretation of a relatively small clinical study, but at least the early signals are promising. Next question operator.

需要注意的是，我們仍然需要進行更大規模的研究。我不希望我們過度擴展對一項相對較小的臨床研究的解釋，但至少早期的信號是有希望的。下一個問題運算符。

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

您的下一個問題來自 Emily Field Barclays。

I just wanted to ask on the business in China. I know you had a -- Innovative Medicines had a very strong quarter in first quarter. But just if you are seeing any impact as we get into second quarter from lockdowns in some of the major cities or just any impact on the broader business.

我只是想問一下在中國的業務。我知道你有一個 - 創新藥物在第一季度有一個非常強勁的季度。但是，如果您在進入第二季度時看到一些主要城市的封鎖帶來的任何影響，或者只是對更廣泛的業務產生任何影響。

Maybe I'll give the China question to Harry. Harry on China.

也許我會把中國問題交給哈利。哈利談中國。

Yes. Thank you, Emily. So overall, we have seen very limited impact in China, as you say, in quarter 1, not at all. And in quarter 2, of course, we are daily monitoring. When there is a city or an area with a risk of lockdown, usually then wholesalers ship a bit earlier to ensure that pharmacies and hospitals on the ground have product. So we don't see really impact, very marginal only. And of course, we continue to monitor that.

是的。謝謝你，艾米麗。所以總的來說，正如你所說，在第一季度，我們在中國看到的影響非常有限，根本沒有。當然，在第 2 季度，我們會進行日常監控。當某個城市或地區有被封鎖的風險時，批發商通常會提早發貨，以確保當地的藥店和醫院有產品。所以我們看不到真正的影響，只是非常微不足道。當然，我們會繼續對此進行監控。

I mean it's one of the reasons why we also kept our forecast assumptions. Should this spread bigger, there would be likely some impact. But we have kept the forecast assumption that we need to see continuation to return to modern prescribing behaviors and China certainly is one of the focus areas for that forecast assumption.

我的意思是，這也是我們保持預測假設的原因之一。如果這種情況擴大，可能會產生一些影響。但我們保留了我們需要看到繼續恢復現代處方行為的預測假設，而中國當然是該預測假設的重點領域之一。

But again, so far, we don't see or very limited impact of this. And we will continue to monitor and provide you an update in quarter 2.

但同樣，到目前為止，我們沒有看到或非常有限的影響。我們將繼續監控並在第 2 季度為您提供更新。

Thanks Harry. Next question operator?

謝謝哈利。下一個問題運算符？

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

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

A couple of questions on Cosentyx. Q1 in the U.S. was a little bit weaker versus what we're expecting and I'm wondering why?

關於 Cosentyx 的幾個問題。美國的第一季度比我們預期的要弱一些，我想知道為什麼？

And then also, just wondering how to think about that product in 2023 as HUMIRA faces biosimilars and as AbbVie tries to lock in formulary placement for that product for HUMIRA. And then Skyrizi, their goal is to preserve volume with HUMIRA. They'll do that through stepped-up rebating. And I'm imagining that puts a fair amount of new pressure on products like Cosentyx and other brands in the category. Is that a fair assessment? And does that kick in only in 2023 and beyond? And does that at all pose a risk to the $7 billion peak sales guidance?

然後，只是想知道如何在 2023 年考慮該產品，因為 HUMIRA 面臨生物仿製藥，並且 AbbVie 試圖為 HUMIRA 鎖定該產品的處方集。然後是 Skyrizi，他們的目標是使用 HUMIRA 保持音量。他們將通過加強回扣來做到這一點。而且我想像這會給 Cosentyx 和該類別中的其他品牌等產品帶來相當大的新壓力。這是一個公平的評價嗎？這是否僅在 2023 年及以後才生效？這是否會對 70 億美元的峰值銷售指導構成風險？

Yes. Thanks, Tim. I mean we remain confident in the $7 billion-plus peak sales guidance. When you look at the dynamics in quarter 1, this is pretty standard for us when we look at reverifications as well as the other elements in the U.S. to get patients confirmed for the remainder of the year. Within the, I would say, dynamics we've historically seen for the brand, we saw good volume growth overall with Cosentyx, particularly in rheumatology.

是的。謝謝，蒂姆。我的意思是，我們對超過 70 億美元的峰值銷售指導充滿信心。當您查看第一季度的動態時，當我們查看重新驗證以及美國的其他要素以在今年剩餘時間確認患者時，這對我們來說是相當標準的。我想說，在我們歷史上看到的品牌動態中，我們看到 Cosentyx 的整體銷量增長良好，特別是在風濕病領域。

That said, in the U.S., we would expect to be growing in the single-digit range in the next 2 years until we get our new indications and new formulations online, which we then think will give us the next wave of acceleration. Cosentyx' additional growth will be driven by our strength in Europe as well as the China NRDL listing and launches elsewhere around the world. So it's a combination of those factors that will drive the growth in the next 2 years. And then the new indications, new formulations, et cetera, will give us the next boost which we believe to get us over that $7 billion mark.

也就是說，在美國，我們預計未來 2 年將在個位數範圍內增長，直到我們在線獲得我們的新適應症和新配方，然後我們認為這將為我們帶來下一波加速。 Cosentyx 的額外增長將由我們在歐洲的實力以及中國 NRDL 上市和在世界其他地方推出的推動。因此，這些因素的結合將推動未來兩年的增長。然後，新的適應症、新的配方等將給我們帶來下一個推動力，我們相信這將使我們超過 70 億美元的大關。

And in terms of the specifics on the HUMIRA dynamics, et cetera, again, I think that's all built into the forecasted numbers that I gave you right there. We feel confident in our overall contracting position given the volumes we currently have with Cosentyx and the positions we have with the relevant formularies. Next question operator.

就 HUMIRA 動力學等細節而言，我認為這一切都包含在我在那裡給你的預測數字中。鑑於我們目前在 Cosentyx 的交易量以及我們在相關處方集上的職位，我們對我們的整體合同職位充滿信心。下一個問題運算符。

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

您的下一個問題來自 Jefferies 的 Peter Welford。

I wanted to come back to Sandoz. You flagged that there were certain onetimers in the quarter that boosted 1Q. I wonder if you could just talk a little bit about those and what the impact of them was?

我想回到山德士。您指出該季度有某些一次性因素提振了 1Q。我想知道你是否可以談談這些以及它們的影響是什麼？

And also, if you look at the margin of Sandoz, obviously, a lot of that was boosted by some of these onetime effects presumably in the easy comp. But can you give us any sort of idea of that sort of significant year-on-year gross -- sorry, core operating income margin improvement? How much of that do you think is actually sustainable and due to some of the efficiency measures within? And how much of it, on the other hand, is just something we should assume is a 1Q onetime effect to help us guide think about the quarters coming forward.

而且，如果你看一下 Sandoz 的利潤，很明顯，其中很大一部分是由這些一次性效果中的一些可能在簡單組合中推動的。但是你能給我們任何關於同比毛利率顯著提高的想法嗎？抱歉，核心營業收入利潤率的提高？您認為其中有多少實際上是可持續的，並且由於內部的一些效率措施？另一方面，其中有多少只是我們應該假設的第一季度一次性效應，以幫助我們指導考慮未來的季度。

Yes. Thanks, Peter. I'll give that one to Harry. Harry?

是的。謝謝，彼得。我會把那個給哈利。哈利？

Yes, Peter, thank you. As you have seen, Sandoz has improved. The margin was a low base prior year by basically 330 basis points, call it 3 margin points to close to 22.84%. Now roughly 2 points of those come from cost of goods, a little under 1% from SG&A and then 0.6% from OIE, where we would have these little divestment gains. As you know, everything above $25 million divestment gains, we would always co-adjust. Sometimes not too often, we have little divestment gains that are below $25 million and then they would stay within OIE. But the overall OIE bucket went from -- we call, correctly, from a minus $11 million OIE effect, total OIE, prior year quarter 1 to plus $7 million OIE number in '22. So the absolute numbers are small, it's $18 million total OIE impact, which is that 0.6% of margin or 4 points of a 26% improvement.

是的，彼得，謝謝。如您所見，Sandoz 有所改進。上一年的利潤率基數較低，基本上低了 330 個基點，稱其為 3 個利潤率點，接近 22.84%。現在，其中大約 2 個點來自商品成本，略低於 1% 來自 SG&A，然後是 0.6% 來自 OIE，我們將獲得這些小的撤資收益。如您所知，所有超過 2500 萬美元的撤資收益，我們都會共同調整。有時，我們很少有低於 2500 萬美元的撤資收益，然後它們將留在 OIE 內。但是整個 OIE 桶從 - 我們正確地稱為 OIE 效應，即 OIE 總額，上一年第一季度，增加了 22 年的 700 萬美元。所以絕對數字很小，它對 OIE 的總影響為 1800 萬美元，即利潤率的 0.6% 或 26% 的改善 4 個百分點。

So the core margin, if you take that little OIE effect out, it's like 22%. So overall, not significant. But of course, we mention it, when the OIE contributes to the overall improvement. So if you take that out, that is not a bad representation, also a very good representation of the underlying profitability.

所以核心利潤率，如果你把那個小小的 OIE 效應排除在外，它就像 22%。所以總體來說，意義不大。但是，當 OIE 對整體改進做出貢獻時，我們當然會提到它。所以如果你把它拿出來，這並不是一個糟糕的表現，也是對潛在盈利能力的一個很好的表現。

And then we have to see over the next quarters how pricing will do and, of course, how much the cough and cold season will be back to fully normal. And the other thing is, of course, given the larger cost of goods, percent of sales, the energy cost and some of the supply price inflation, how much we offset from productivity. Overall for the company, I'm very confident we do that. Within Sandoz, we have to watch that given the bigger part of the P&L was Innovative Medicines.

然後我們必須看看在接下來的幾個季度定價將如何發揮作用，當然，咳嗽和感冒季節將恢復到完全正常的程度。另一件事當然是考慮到更大的商品成本、銷售百分比、能源成本和一些供應價格通脹，我們從生產力中抵消了多少。總體而言，對於公司而言，我非常有信心做到這一點。在山德士內部，我們必須注意，鑑於損益表的較大部分是創新藥物。

Terrific. Thanks, Harry. Next question operator.

了不起。謝謝，哈利。下一個問題運算符。

Your next question comes from the line of Keyur Parekh from Goldman Sachs.

您的下一個問題來自高盛的 Keyur Parekh。

Vas, if I look at the last 6 months since you reported the third quarter on October 27 -- 26, you've announced the strategic review for Sandoz, you've done the Roche stake sale, you've reorganized the Innovative Medicines business and today announced this new kind of initiative on kind of big growth kind of a new seat on the ECN. Just wondering kind of -- is there a common theme across these 4 initiatives? It seems that you're doing a lot on a very short period of time. So just trying to get a sense for what's driving these measures.

Vas，如果我看一下自您於 10 月 27 日至 26 日報告第三季度以來的過去 6 個月，您已宣布對 Sandoz 進行戰略審查，您已完成羅氏股份出售，您已重組創新藥物業務今天宣布了這種關於在 ECN 上的新席位的大增長的新舉措。只是想知道這 4 項舉措是否有共同的主題？看起來你在很短的時間內做了很多事情。因此，只是想了解推動這些措施的原因。

Yes. Thanks, Keyur. Look, our goal is to drive outstanding company performance for the benefit of our shareholders and benefit of patients and society. And I think all of these moves on the first order are creating value for our shareholders. Clearly, evaluating if Sandoz fits within the group or is better as a stand-alone company, and we've demonstrated with Alcon, we do that in a thoughtful way. In the case of Alcon, we created an outstanding stand-alone company. We'll evaluate the same with Sandoz.

是的。謝謝，凱爾。看，我們的目標是為了股東的利益、患者和社會的利益，推動公司的卓越表現。我認為所有這些一開始的舉措都在為我們的股東創造價值。顯然，評估山德士是否適合該集團或作為一家獨立公司是否更好，我們已經與愛爾康一起證明了這一點，我們以深思熟慮的方式做到了這一點。就愛爾康而言，我們創建了一家出色的獨立公司。我們將對 Sandoz 進行同樣的評估。

The sale of the Roche stake and buying back our own shares in a place where we view our shares are undervalued relative to the potential of the company and the growth that we have confidence in and that our Board has confidence in, again, a value-creating move.

出售羅氏股份並在我們認為我們的股票相對於公司的潛力和我們有信心的增長以及我們的董事會有信心再次被低估的地方回購我們自己的股票價值-創造動作。

Reorganizing so that we become much more agile, efficient, take out costs out of the system, improve our overall operating performance both on the top and bottom line generate differential growth. Again, I think a very logical thing to do to increase shareholder returns and value and improve the performance of the company.

重組使我們變得更加敏捷、高效，從系統中降低成本，提高我們的整體運營績效，無論是在頂線還是底線，都會產生差異化的增長。同樣，我認為增加股東回報和價值並改善公司業績是一件非常合乎邏輯的事情。

And then lastly, you referenced, it was kind of part of the reorganization, but the creation of the strategy and growth function is to create a consistent top-level view of do what is the right things we need actions we need to take on our internal pipeline versus the external opportunities that we have before us in order to keep a consistent growth as we've guided of the mid-single 4% to 5% range in the coming years and then above peer median in the back half of the decade.

最後，您提到，這是重組的一部分，但戰略和增長職能的創建是為了創建一個一致的頂層視圖，即做正確的事情我們需要採取的行動內部管道與擺在我們面前的外部機會的對比，以保持持續增長，因為我們在未來幾年指導了中單 4% 到 5% 的範圍，然後在十年後半期高於同行中位數.

So it's about performance, it's. About creating shareholder returns. And it's about driving more impact of the company on medicine. Thank you, Keyur. Next question operator.

所以這是關於性能的，它是。關於創造股東回報。這是為了推動公司對醫藥產生更大的影響。謝謝你，凱爾。下一個問題運算符。

Your next question comes from the line of Florent Cespedes from Societe Generale.

您的下一個問題來自法國興業銀行的 Florent Cespedes。

A quick follow-up on Sandoz, please. Could you elaborate on the performance of the different businesses, if you see any inflection point, especially in the U.S. where you used to be under pressure from -- strong pricing pressure there. So if you start to see any inflection point could be very helpful.

請快速跟進 Sandoz。如果您看到任何拐點，您能否詳細說明不同業務的表現，特別是在您曾經承受壓力的美國——那裡有強大的定價壓力。因此，如果您開始看到任何拐點可能會非常有幫助。

Yes. Thanks, Florent. So overall, Sandoz had -- is now getting back to growth globally, but particularly, I would say Europe has had strong underlying performance, driven both by biosimilars and small molecules. Also good performance in our international, as we call it, emerging markets plus Japan.

是的。謝謝，弗洛倫特。因此，總體而言，山德士已經 - 現在在全球範圍內恢復增長，但特別是，我想說歐洲在生物仿製藥和小分子藥物的推動下有著強勁的潛在表現。在我們所說的國際新興市場和日本也有良好的表現。

The U.S. still declined in the single-digit range, but we currently have an outlook that we expect in -- over the course of '22 and the first part of '23 to really bottom out on the U.S. oral solids business which will then allow us to build on biosimilars and new launches to get back to growth. And we expect coming out of '23 and then into the mid-2020s, '24, '25, et cetera, for the U.S. business to really grow on the back of biosimilar launches as well as more first to files in the overall injectable and small molecule pipeline.

美國仍然在個位數範圍內下降，但我們目前有一個我們預期的前景——在 22 年和 23 年上半年，美國口服固體藥物業務將真正觸底反彈，屆時將允許我們將在生物仿製藥和新產品發布的基礎上恢復增長。我們預計從 23 年開始，然後進入 2020 年代中期、24 年、25 年等，美國業務將在生物仿製藥的推出以及更多首先提交整體注射劑和小分子管道。

So that's the dynamic we see. But certainly still some ways to go -- a little bit more to go in the U.S. to get to the bottom, but that should be coming and then we get back to growth. Europe is a very solid footing. And in international markets, we generally tend to do well. Next question operator.

這就是我們看到的動態。但肯定還有一些路要走——在美國還有一些路要走才能觸底，但這應該會到來，然後我們就會恢復增長。歐洲是一個非常穩固的基礎。在國際市場上，我們通常會做得很好。下一個問題運算符。

Your next question comes from Sarita Kapila from Morgan Stanley.

您的下一個問題來自摩根士丹利的 Sarita Kapila。

How should we think about the Lu-PSMA opportunity, particularly given there's been a restriction to a Gallium imaging agent versus Gallium and [SAC] that could just limit the number of accessible patients in the overall commercial opportunity.

我們應該如何考慮 Lu-PSMA 的機會，特別是考慮到鎵顯像劑與鎵和 [SAC] 相比存在限制，這可能只會限制整個商業機會中可獲得的患者數量。

Yes. Thanks. For Lu-PSMA, we have currently worked very hard on [locameto], our Gallium agent, where we are -- we've already secured agreements to have this agent distributed widely amongst diagnostic centers. So we expect over the coming months to be able to relieve any constraint on imaging these patients to enable uptake of the medicine. And as I mentioned, we're leveraging the Lutathera footprint, but also beginning to work already in bringing additional centers online in order to fully capture the earlier-line opportunities. We're going to need to move from roughly 250 centers where we currently service RLTs to get to over 500 centers, roughly 550 centers. That's part of a multiyear effort.

是的。謝謝。對於 Lu-PSMA，我們目前非常努力地研究 [locameto]，我們的鎵代理，我們所在的地方——我們已經達成了讓這種代理在診斷中心廣泛分佈的協議。因此，我們預計未來幾個月將能夠解除對這些患者進行成像的任何限制，以使藥物能夠被吸收。正如我所提到的，我們正在利用 Lutathera 的足跡，但也已經開始努力讓更多的中心上線，以充分抓住早期的機會。我們需要從目前為 RLT 提供服務的大約 250 個中心轉移到 500 多個中心，大約 550 個中心。這是多年努力的一部分。

As a reminder, we expect Pluvicto in this later-line, third, fourth line prostate -- metastatic prostate cancer setting to be around $0.5 billion to $750 million opportunity. And really the more significant opportunity would come from the very large patient populations in the earlier-line settings where we have a readout in the second half of this year as well as a readout next year within -- current evaluation ongoing to expand into additional lines of therapy to see if the medicine can be more broadly used.

提醒一下，我們預計 Pluvicto 在這種後線、三線、四線前列腺癌 - 轉移性前列腺癌環境中的機會約為 5 億至 7.5 億美元。實際上，更重要的機會將來自早期設置中的大量患者群體，我們將在今年下半年和明年進行讀數——目前的評估正在進行中，以擴展到其他線治療，看看藥物是否可以更廣泛地使用。

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

您的下一個問題來自 Cowen 的 Steve Scala。

My recollection is that NATALEE readout initially was 2023 but that was moved up to 2022. That may have been announced as early as 2019 due to confidence in an interim look. So what changed since 2019 when things were apparently progressing very quickly? And if the current slow event accumulation is due to delayed visits and therefore delayed event detection as a result of the pandemic, how would that impact the final analysis?

我的回憶是，NATALEE 讀數最初是 2023 年，但後來移到了 2022 年。由於對臨時外觀的信心，這可能早在 2019 年就宣布了。那麼自 2019 年事情顯然進展非常迅速以來發生了什麼變化？如果當前緩慢的事件積累是由於訪問延遲，因此大流行導致事件檢測延遲，這將如何影響最終分析？

Yes. Thanks, Steve; so since 2019, we increased the sample, if my recollection is correct, we increased the sample size of the study up. We certainly increased our overall time line. I don't recall exactly, but I'll look into the point you raised around what we said previously on interim, certainly a very fair challenge. But with the revised 5,000 patients in the study and 500 events, we've been forecasting on an ongoing basis.

是的。謝謝，史蒂夫；所以從2019年開始，我們增加了樣本，如果我沒記錯的話，我們增加了研究的樣本量。我們當然增加了我們的整體時間線。我不記得確切，但我會研究你提出的關於我們之前所說的臨時問題，當然這是一個非常公平的挑戰。但隨著研究中修改後的 5,000 名患者和 500 起事件，我們一直在進行預測。

One thing that is important to note is we did a very detailed look over quarter 1 to ensure that we've collected all events. And to our best assessment, we don't believe this is -- our current event rate is due to delayed reporting of events or over COVID impacts. We believe now we have a clean look at the study and that the event rate is below our projected event rate. Unrelated to operational concerns, but just related to the events accrual rate in the study.

需要注意的重要一件事是，我們對第一季度進行了非常詳細的查看，以確保我們收集了所有事件。根據我們的最佳評估，我們不認為這是 - 我們目前的事件發生率是由於延遲報告事件或超過 COVID 影響。我們相信現在我們對這項研究有了清晰的了解，並且事件發生率低於我們預計的事件發生率。與運營問題無關，而僅與研究中的事件發生率有關。

And of course, we'll keep you updated, but I think our team did a pretty rigorous job over the recent months to really ensure we have all of the best data on hands to provide you this update. Next question operator.

當然，我們會及時通知您，但我認為我們的團隊在最近幾個月做了非常嚴格的工作，以真正確保我們擁有所有最好的數據來為您提供此更新。下一個問題運算符。

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

您的下一個問題來自瑞銀的勞拉·薩特克利夫 (Laura Sutcliffe)。

Just perhaps in the light of your Chief Strategy and Growth Officer appointment, maybe you could touch on some comments you made on your recent call when you announced your business reorg on the idea that you're good at getting your pipeline to market but maybe need to get better at getting very big drugs to market. So as not too many steps to remove from saying that you might want to think about reprioritizing your Innovative Medicines pipeline. So could you maybe just talk about your process for deciding when not to pursue projects and whether you think there's such a thing as too big of a pipeline. And specifically, maybe you could talk about how your colleagues are incentivized to shut projects down rather than keeping them alive.

或許根據您任命的首席戰略和增長官，也許您可以談談您在最近的電話會議上發表的一些評論，當時您宣布進行業務重組，認為您擅長將管道推向市場，但可能需要以便更好地將非常大的藥物推向市場。因此，您可能需要考慮重新確定您的創新藥物管道的優先級，因此無需採取太多步驟。所以你能不能談談你決定什麼時候不追求項目的過程，以及你是否認為管道太大了。具體來說，也許你可以談談你的同事是如何被激勵關閉項目而不是讓它們保持活力的。

Yes. Thanks, Laura. A big question there. So a few points -- few points I'd raise, kind of going step by step.

是的。謝謝，勞拉。那裡有一個大問題。所以有幾點——我要提出幾點，有點循序漸進。

First, we do have, I think, a rigorous approach to prioritizing our pipeline, particularly after proof-of-concept readout, through submission. We not only look at scientific factors, scientific tractability but also look at, of course, NPV, ENPV, peak sales, return on capital employed, probablized return on capital employed. But I think it's important that we have very good analytics to back up those assessments of those molecules and then make sure that, also versus the competitive set, we've looked at them with silver eyes. So I think that's one thing we want to upskill in the organization, to have really outstanding information with which to make those decisions and also evaluate against other external opportunities.

首先，我認為，我們確實有一種嚴格的方法來優先考慮我們的管道，特別是在概念驗證讀出之後，通過提交。我們不僅關注科學因素、科學易處理性，當然還關注 NPV、ENPV、峰值銷售、使用資本回報率、使用資本的可能回報率。但我認為重要的是，我們有非常好的分析來支持對這些分子的評估，然後確保與競爭對手相比，我們已經用銀色的眼睛看著它們。所以我認為這是我們想要在組織中提陞技能的一件事，擁有非常出色的信息來做出這些決定並評估其他外部機會。

Then on top of that, I've previously stated that we've increased the thresholds that we're putting in place at an asset level, not necessarily at an indication level. But we want assets that have the potential to be multibillion-dollar assets. That will mean that by exception we might go after some others when they are strategically -- have a good strategic fit, but it's certainly our goal to find multibillion-dollar assets. And then to have the discipline to say no when assets don't meet those thresholds.

最重要的是，我之前說過我們已經提高了我們在資產級別設置的閾值，而不一定是在指示級別。但我們想要有潛力成為數十億美元資產的資產。這將意味著，在例外情況下，我們可能會在戰略上追逐其他一些人——具有良好的戰略契合度，但我們的目標肯定是找到數十億美元的資產。然後當資產不符合這些門檻時，要有紀律說不。

We've also endeavored over the recent years to focus down on therapeutic areas that we really believe we can build scale in for the long term. Clearly, as Andrew mentioned earlier on the call, cardiovascular is a top priority. Immunology, given all of the various medicines we have in the pipeline on top of Cosentyx, of course, we have our BTK inhibitor. We have VAY as well as other assets now progressing through also a priority.

近年來，我們還努力專注於我們真正相信我們可以長期擴大規模的治療領域。顯然，正如安德魯之前在電話會議上提到的，心血管是重中之重。免疫學，考慮到我們在 Cosentyx 之上的所有各種藥物，當然，我們有我們的 BTK 抑製劑。我們有 VAY 以及其他資產現在也在優先處理中。

Neuroscience, given our presence in multiple sclerosis but also emerging assets we have in neuroscience. And of course, solid tumors and hematology.

神經科學，考慮到我們在多發性硬化症中的存在，以及我們在神經科學領域的新興資產。當然，還有實體瘤和血液學。

So 5 kind of pillar of TAs. Of course, we have some medicines in areas like ophthalmology and respiratory. But we want to have our focus be to build scale in those 5 priority TAs and again have the discipline always to chase anything else that might be around in other therapeutic areas.

所以 5 種 TA 的支柱。當然，我們在眼科和呼吸系統等領域也有一些藥物。但我們希望我們的重點是在這 5 個優先 TA 中建立規模，並再次擁有始終追逐其他治療領域可能存在的任何其他東西的紀律。

So I think with those factors in place, we can, over time, really ensure we have the right pipeline to drive growth for our company. As I mentioned, over 20-plus multibillion dollar assets to our current assessment. But certainly, we'll ask Ronny to reassess that and give us an honest look and to honestly tell us where we're at and what do we need to do and where does the external environment give us opportunity and where maybe doubling down on other internal assets give us an opportunity as well.

所以我認為有了這些因素，隨著時間的推移，我們可以真正確保我們有正確的渠道來推動我們公司的增長。正如我所提到的，我們目前的評估有超過 20 多億美元的資產。但可以肯定的是，我們會要求 Ronny 重新評估這一點，誠實地看待我們，誠實地告訴我們現在所處的位置，我們需要做什麼，外部環境在哪裡給了我們機會，以及在哪些方面可能會加倍下注內部資產也給了我們機會。

So a lot of, of course, ongoing work, but I think we're on the right track. And we're hopeful and optimistic that with Ronny coming onboard, we can even accelerate on that journey. Next question operator.

當然，還有很多正在進行的工作，但我認為我們走在正確的軌道上。我們對羅尼的加入充滿希望和樂觀，我們甚至可以加速這一旅程。下一個問題運算符。

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

您的下一個問題來自古根海姆證券公司的 Seamus Fernandez。

So, Vas, maybe first question is just how you see the PCSK9 environment evolving in the context of Merck's oral PCSK9 where we're seeing some pretty robust data. I'd love to just kind of get your thoughts there and then the evolution of the market as we see it for an injectable therapy.

所以，Vas，也許第一個問題是您如何看待 PCSK9 環境在默克口服 PCSK9 的背景下演變，我們看到了一些非常可靠的數據。我很想听聽你的想法，然後是我們看到的注射療法市場的演變。

And then second, just wanted to get a better sense of the impact of inflation and how -- what levers Novartis has the capability to pull to keep up with inflation? Do you see a pricing environment in the United States that can actually facilitate price increases? Because it appears that, that won't necessarily be available in international markets. But maybe you can just correct us where our thinking might be wrong as it relates to the ability for Novartis and the rest of the pharmaceutical industry to keep up with inflation.

其次，只是想更好地了解通脹的影響以及如何——諾華有能力拉動哪些槓桿來跟上通脹的步伐？您是否看到美國的定價環境實際上可以促進價格上漲？因為看起來，這不一定在國際市場上可用。但也許你可以糾正我們的想法可能是錯誤的，因為它關係到諾華和其他製藥行業跟上通貨膨脹的能力。

Yes. Thanks, Seamus. I think on the PCSK9, first, it's important to take a step back and look at the global unmet need. I mean there's an estimated 16 million-plus patients around the world who have ASCVD that are not adequately controlled with current agents. So big, big opportunity. In the U.S. alone, 18 million to 20 million patients. So there is plenty of space here for many agents. And even if we capture a fraction of that with Leqvio, we have a very sizable -- sizable medicine. That I think, first, is important as context.

是的。謝謝，西莫。我認為在 PCSK9 上，首先，重要的是退後一步，看看全球未滿足的需求。我的意思是，全世界估計有超過 1600 萬患有 ASCVD 的患者無法用當前的藥物進行充分控制。好大好大的機會。僅在美國，就有 1800 萬到 2000 萬患者。所以這裡有足夠的空間供許多代理商使用。即使我們用 Leqvio 捕獲了其中的一小部分，我們也有一個非常可觀的藥物。我認為，首先，作為背景很重要。

It's also important to note with Leqvio, our goal is to access that broader market. I mean if you look at current PCSK9 monoclonal antibodies, they're accessing a fraction of this market. So our goal is to grow the market. And with bringing forward a twice-a-year Part B medicine and then setting up the infrastructure in cardiovascular care with Part B clinics but then also with population health agreements around the world, we think it's a pretty unique value proposition for an asymptomatic disease to have a twice a year therapeutic versus having chronic therapies where we know that patients generally don't comply with their statins or ezetimibe or (inaudible) -related therapies.

同樣重要的是要注意 Leqvio，我們的目標是進入更廣闊的市場。我的意思是，如果您查看當前的 PCSK9 單克隆抗體，它們正在進入這個市場的一小部分。所以我們的目標是擴大市場。通過推出一年兩次的 B 部分藥物，然後通過 B 部分診所建立心血管護理基礎設施，然後還與世界各地的人口健康協議達成一致，我們認為對於無症狀疾病來說，這是一個非常獨特的價值主張一年兩次治療與慢性治療相比，我們知道患者通常不遵守他們的他汀類藥物或依折麥布或（聽不清）相關療法。

So that's the broad strategy. So when I think about orals or monthly injectables, I don't think it changes our strategy and our belief that in the long run, the ability to provide twice-a-year medicines through the physician buy-and-bill and Part B model in the U.S. and population health around the world is a long-term opportunity to address this relatively vast market opportunity.

這就是廣泛的戰略。因此，當我想到口服或每月注射劑時，我認為它不會改變我們的策略和我們的信念，即從長遠來看，通過醫生買單和 B 部分模式提供一年兩次藥物的能力在美國和世界各地的人口健康方面是應對這一相對巨大的市場機會的長期機會。

And I mean, let's see what happens. Of course, as you know, in cardiovascular disease, it's a long journey to get from early clinical data ultimately to the patients at the other side of the long journey. Now in terms of inflation, Harry?

我的意思是，讓我們看看會發生什麼。當然，如您所知，在心血管疾病中，從早期臨床數據最終到達長途旅程另一端的患者是一個漫長的旅程。現在就通貨膨脹而言，哈利？

Yes. Thank you. And thank you, Seamus, for the question. Very important, of course, in the geopolitical environment we are living. I think I would start with that usually also my experience and given our cost structures, inflationary pressures can be usually well balanced with productivity measures. And so we are not very energy-intensive.

是的。謝謝你。謝謝你，Seamus，提出這個問題。當然，在我們所處的地緣政治環境中非常重要。我想我通常也會從我的經驗開始，考慮到我們的成本結構，通脹壓力通常可以與生產力指標很好地平衡。所以我們不是很耗能。

On the other hand, of course, if inflationary measures get into the personnel cost side which over time will happen here or there, I think we have very good productivity programs in place to offset that.

另一方面，當然，如果通貨膨脹措施涉及人員成本方面，隨著時間的推移會在這里或那裡發生，我認為我們有非常好的生產力計劃來抵消這一點。

And of course, also our move transformation for growth which combines, for example, our shared service, together with our manufacturing supply chain, there, our leader, (inaudible) and his team will further strengthen the impact of our procurement organization across our complete external spend. So that's one element. And overall, I think we are very well positioned to fight any potential bottom line effect off with increased productivity measures.

當然，還有我們的增長轉型，例如，我們的共享服務以及我們的製造供應鏈，我們的領導者（聽不清）和他的團隊將進一步加強我們的採購組織在我們整個外部支出。這是一個要素。總體而言，我認為我們已經做好準備，通過提高生產力措施來消除任何潛在的底線影響。

In terms of pricing power, I mean, as you described, it's mainly in the U.S. given our portfolio and business. We have been, within our pricing policies on key brands, increasing in the mid-single to mid- to high single-digit range in list prices. (inaudible) depending on the rebates, we have to get a plus or minus low single-digit environment. Of course, we look at that also from a competitive standpoint. But of course, we would always price with our commitments.

就定價能力而言，我的意思是，正如你所描述的，考慮到我們的投資組合和業務，它主要在美國。在我們對主要品牌的定價政策中，我們一直在標價的中個位數至中個位數至中高個位數範圍內上漲。 （聽不清）根據回扣，我們必須獲得一個正負低個位數的環境。當然，我們也是從競爭的角度來看的。但是，當然，我們總是會以我們的承諾為代價。

And ex-U.S., there is some limited pricing increases potential, but much less and usually more for Sandoz. We have also some OTC elements in the Sandoz business.

在美國以外的地區，價格上漲的潛力有限，但山德士的潛力要小得多，而且通常更多。我們在山德士業務中也有一些場外交易元素。

But I think key is for us that we do not only try to offset (inaudible) pricing, but with significant productivity measures as well as via procurement, ensuring that our suppliers do the same in their productivity efforts and offset inflation as much as possible.

但我認為，對我們而言，關鍵在於我們不僅要嘗試抵消（聽不清）定價，還要採取重要的生產力措施以及通過採購，確保我們的供應商在生產力方面做出同樣的努力並儘可能抵消通貨膨脹。

Thanks, Harry. Next question operator.

謝謝，哈利。下一個問題運算符。

Your next question comes from the line of Kerry Holford from Berenberg.

您的下一個問題來自 Berenberg 的 Kerry Holford。

A question on M&A. Given the recent pullback in valuations and seemingly tough [IPO margins,] I wonder, Vas, if you can give us your latest perspective on the environment. In the context of the broader market moves, are you noting more external interest, greater willingness to discuss potential collaborations and M&A opportunities?

關於併購的問題。鑑於最近估值的回落和看似艱難的 [IPO 利潤率]，我想知道 Vas，您能否向我們提供您對環境的最新看法。在更廣泛的市場變動的背景下，您是否注意到更多的外部利益，更願意討論潛在的合作和併購機會？

Yes. Thanks, Kerry. When you look at, of course, the pullback in the XBI and I think I've heard various data points but many companies trading below their even the cash they have on hand, I think it certainly points to doing the disciplined look. But I think first and foremost, we have to be science-driven and really ask is there science and good data to support an acquisition? And I think there, as we're seeing in the broader biotech market, it's been challenging. And then I think a lot of data readouts have pointed to the fact that it is hard to find novel drugs effectively.

是的。謝謝，克里。當然，當你看到 XBI 的回調時，我想我已經聽到了各種數據點，但許多公司的交易價格甚至低於他們手頭的現金，我認為這肯定指向了謹慎的態度。但我認為首先，我們必須以科學為導向，並真正詢問是否有科學和好的數據來支持收購？而且我認為，正如我們在更廣泛的生物技術市場中看到的那樣，這一直具有挑戰性。然後我認為很多數據讀數都指出了一個事實，即很難有效地找到新藥。

So we continue to look. Our focus remains, as I've guided in recent quarters, into the sub $2 billion space to see if there are attractive methods. And when there are good deals out there, we're, of course, looking to do them.

所以我們繼續看。正如我最近幾個季度所指導的那樣，我們的重點仍然是低於 20 億美元的空間，看看是否有有吸引力的方法。當那裡有好交易時，我們當然會尋求去做。

I do think over the course of this year as well, expectations amongst sellers, so to speak, will adjust. And there may be more openness to think about how partnerships and M&A and business development could be conducted. So there could be more activity certainly in the sector second half of the year. And we'll, of course, be doing our part to diligently keep screening and see what's out there that could be attractive. Next question operator.

我確實認為，在今年的過程中，賣家的期望，可以說，將會調整。並且可能會更加開放地思考如何進行合作夥伴關係、併購和業務發展。因此，今年下半年該行業肯定會有更多活動。當然，我們會儘自己的一份力量努力繼續篩選，看看有什麼可能有吸引力。下一個問題運算符。

Your next question comes from the line of Naresh Chouhan from Intron Health.

您的下一個問題來自 Intron Health 的 Naresh Chouhan。

Just one on the impact of inflation on cost base, following off from Seamus' question. Just a question on the phasing of the impact of inflation on the cost lines. Because I'm guessing you have a bunch of contracts that are longer term and some suppliers may yet have to raise prices. So should we be thinking about inflationary impacts on costs in H2? Or will that be pushed into next year?

在 Seamus 的問題之後，只有一個關於通貨膨脹對成本基礎的影響。只是一個關於通貨膨脹對成本線影響的階段性的問題。因為我猜你有一堆長期的合同，一些供應商可能還不得不提高價格。那麼我們是否應該考慮通脹對下半年成本的影響？還是會推遲到明年？

And then linked to that, when you formulated your guidance earlier on in the year, do you feel the inflationary pressures you're seeing now are, I mean, is fully accounted for?

與此相關的是，當您在今年早些時候制定指導方針時，您是否覺得您現在看到的通脹壓力已被完全考慮在內？

Thanks, Naresh. Harry?

謝謝，納雷什。哈利？

Yes. Thank you, Naresh. Yes, we have seen some in quarter 1 on energy, right, like probably most others. And -- but again, we are not so energy-intensive. And when we basically forecast out the energy part as well as the supplier base, as you say, contracts a bit further out, we see roughly 1 point of (inaudible) as the risk around that. But we have offsetting measures to offset that and be well within our guidance.

是的。謝謝你，納雷什。是的，我們在第一季度看到了一些關於能源的內容，對，可能和大多數其他人一樣。而且——但同樣，我們並不是那麼耗能。當我們基本上預測能源部分以及供應商基礎時，正如你所說，收縮得更遠一點，我們認為大約 1 點（聽不清）作為風險。但我們有抵消措施來抵消這一點，並且完全在我們的指導範圍內。

And then of course, the other question is, of course, will this stay here, this situation, for a long time? Of course, at the moment, we assume, from a forecasting standpoint, it will remain for the rest of the year. And then beyond this year, I would say, again, we have many levers of productivity to offset that so that we are also very confident in our mid- to long-term opt margin guidance which we did together with the announcement of transforming growth initiatives.

然後當然，另一個問題是，當然，這種情況會在這裡停留很長時間嗎？當然，目前，我們假設，從預測的角度來看，它將在今年剩下的時間裡保持不變。然後在今年之後，我要再說一次，我們有許多生產力槓桿來抵消這一點，因此我們對我們的中長期選擇保證金指導也非常有信心，我們在宣布轉型增長計劃時所做的這些指導.

So overall, I would say, given our cost structures, manageable. But of course, we'll ask for some increased efforts to do so, but we are well prepared.

所以總的來說，我想說，考慮到我們的成本結構，是可控的。當然，我們會要求為此付出更大的努力，但我們已經做好了充分的準備。

Thanks Harry. Next question operator.

謝謝哈利。下一個問題運算符。

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

您的下一個問題來自法國巴黎銀行的 Richard Parkes。

Just on your Innovative Medicines, 40% plus margin target, I'm trying to square that with some of your peers. That don't seem to feel that's a sustainable level of profitability. And given that you're a therapeutically diversified business, I would have thought that would lead to structurally slightly lower overall margins. I wondered if you could just highlight us what we're missing or what's unique about Novartis that we're overlooking?

就您的創新藥物，40% 的利潤率目標而言，我正試圖與您的一些同行達成一致。這似乎不是一個可持續的盈利水平。鑑於您是一家治療多元化的企業，我原以為這會導致整體利潤率在結構上略低。我想知道您是否可以只強調我們所缺少的或我們忽略的諾華的獨特之處？

And just following on from that, Keyur mentioned you've been demonstrated willingness to grapple challenges within the business in recent times. And I just wonder if you could update us on your thoughts of your presence in some of your more subscale therapeutic categories like respiratory and ophthalmology. Just wondering whether that might be baked into achievement as that margin target exiting those areas.

緊接著，Keyur 提到你最近表現出了應對業務挑戰的意願。我只是想知道您是否可以向我們更新您對您在一些更小規模的治療類別（如呼吸和眼科）中的存在的看法。只是想知道這是否會隨著利潤目標退出這些領域而成為成就。

Yes. Thanks, Richard. When we look at our approach longer term, and we want to maintain R&D in the 20% range as we've guided, that we're always willing -- 20% of IM sales that, of course, we're always willing to go up based on opportunities if they're highly attractive. And I think you see our peer set moving around some well below that target, some well above that target, but I still think in the long run being in that 20% range is a solid investment level given the size of the company.

是的。謝謝，理查德。當我們從長遠來看我們的方法時，我們希望按照我們的指導將研發保持在 20% 的範圍內，我們總是願意——當然，我們總是願意的 20% 的 IM 銷售額如果機會非常有吸引力，就會根據機會上升。我認為你看到我們的同行在一些遠低於該目標的情況下移動，一些遠高於該目標，但我仍然認為從長遠來看，考慮到公司的規模，在 20% 的範圍內是一個可靠的投資水平。

When you think about our SG&A, we want to be at the median or better in the sector over time. And we certainly see peers who are far more efficient than us in the SG&A areas. So when we take our current IM margin, which is in that 36% to 37% range and we see the opportunities [that] come with technology, with rationalizing our footprint, with the opportunity to hopefully leverage capabilities in market, we think we can get those 4 to 5 points out of SG&A to get us into that 40% range on a sustainable basis. I can't speak to how our peers look at it. Of course, it does require you to rethink your business model. And I think what we're working on right now in IM as part of this new setup is to rethink our country's footprint and our approach to go to market in country to make it much more flexibilized, much more technology-driven, and in the long-run, we hope more sustainable to enable us to launch products highly efficiently. And that's where the opportunity comes from. It's certainly not from cutting R&D and our innovation engine, it's coming from that other part of our P&L and that's how we think about it.

當您考慮我們的 SG&A 時，我們希望隨著時間的推移處於該行業的中位數或更好的水平。我們當然會看到在 SG&A 領域比我們更有效率的同行。因此，當我們採用當前 36% 到 37% 的 IM 利潤率時，我們看到技術帶來的機會，合理化我們的足跡，有機會利用市場能力，我們認為我們可以從 SG&A 中獲得這 4 到 5 分，以使我們在可持續的基礎上進入 40% 的範圍。我無法談論我們的同齡人如何看待它。當然，它確實需要你重新考慮你的商業模式。我認為，作為新設置的一部分，我們現在在 IM 中所做的工作是重新思考我們國家的足跡和我們在國內進入市場的方法，使其更加靈活、更加技術驅動，並且在從長遠來看，我們希望更具可持續性，使我們能夠高效地推出產品。這就是機會的來源。這當然不是來自削減研發和我們的創新引擎，而是來自我們損益表的其他部分，這就是我們的想法。

On the portfolio optimization, nothing new to announce other than I think it's certainly -- we are looking as well as part of this transformation how to optimize our commercial footprint as well as our development footprint based on the new model of a single IM unit. As part of that, of course, we're looking at relevant TAs. And of course, in respiratory, we're largely limited to Xolair, with a small presence in QB in Health Therapeutics. And in ophthalmology, really Lucentis and Beovu. So it's naturally part of our thinking how to optimize these 2 areas. That's certainly something we'll be working on over the course of this year.

在投資組合優化方面，除了我認為肯定的以外，沒有什麼新的要宣布的——我們正在尋找這種轉變的一部分，如何基於單個 IM 單元的新模型優化我們的商業足跡以及我們的開發足跡。當然，作為其中的一部分，我們正在研究相關的助教。當然，在呼吸系統方面，我們主要限於 Xolair，在 Health Therapeutics 的 QB 中存在少量。在眼科領域，真的是 Lucentis 和 Beovu。因此，如何優化這兩個領域自然是我們思考的一部分。這當然是我們將在今年努力的事情。

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

您的下一個問題來自美國銀行的 Graham Parry。

So just a question on Pluvicto. So you talked about the fact that your own gallium-based diagnostic is helping or you hope to help with the uptake. But there is some feedback that the 18x diagnostics are easier to use, easier to manufacture. I noticed that you had done a collaboration deal with an 18x diagnostic manufacturer. So can that be back applied to the label for the vision indication and/or can you add it to PSMA IV and PSMA addition trials? Or would this just be for a front line?

所以只是一個關於 Pluvicto 的問題。所以你談到了你自己的基於鎵的診斷正在幫助或者你希望幫助吸收這一事實。但是有一些反饋說 18x 診斷更容易使用，更容易製造。我注意到您與一家 18x 診斷製造商達成了合作協議。那麼可以將其重新應用於視覺指示標籤和/或您可以將其添加到 PSMA IV 和 PSMA 添加試驗中嗎？或者這只是為了前線？

Yes. Thanks, Graham. So for the current launch, we are limited to the diagnostic on label. But certainly, for the follow-up indications, we're working hard to put together the relevant data package with FDA to hopefully broaden the range of diagnostic agents that can be used. You can imagine that as part of our discussions with the FDA, we put together our best arguments to be as broad as possible on diagnostic options for physicians, but at least for now on this first indication, but we'll be limited to the Gallium agents. But over time, we hope to expand that, especially as we go into the larger market segments in the coming years.

是的。謝謝，格雷厄姆。因此，對於當前的發布，我們僅限於標籤上的診斷。但可以肯定的是，對於後續適應症，我們正在努力與 FDA 一起整理相關數據包，以期擴大可使用的診斷試劑的範圍。您可以想像，作為我們與 FDA 討論的一部分，我們將我們最好的論點放在一起，盡可能廣泛地為醫生提供診斷選擇，但至少目前是第一個適應症，但我們將僅限於鎵代理。但隨著時間的推移，我們希望擴大這一點，尤其是當我們在未來幾年進入更大的細分市場時。

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

您的下一個問題來自瑞士信貸的 Matthew Weston。

Vas, it's a question about buy-and-bill. So since you acquired the Medicines Company, you've educated us all on the advantages of buy-and-bill and how you hope in the U.S. it's going to help with the commercialization of Leqvio. I'm curious how we should think about buy-and-bill when you're up against it yourself in a competitive environment. And in particular, I'm thinking of iptacopan versus Soliris/Ultomiris and other high-value infused drugs but also Kesimpta versus Ocrevus. Does that put a meaningful barrier in the commercialization potential of those molecules?

Vas，這是一個關於買單的問題。因此，自從您收購了 Medicines Company 以來，您已經向我們所有人介紹了購買和賬單的優勢，以及您希望在美國如何幫助 Leqvio 的商業化。我很好奇當你在競爭激烈的環境中自己面對買單時，我們應該如何考慮。特別是，我正在考慮 iptacopan 與 Soliris/Ultomiris 和其他高價值輸注藥物，以及 Kesimpta 與 Ocrevus。這是否對這些分子的商業化潛力設置了有意義的障礙？

Yes, absolutely. Thanks, Matthew. So one -- I think it's very situation-specific. So let's take each one of those in turn.

是的，一點沒錯。謝謝，馬修。所以一個 - 我認為這是非常具體的情況。因此，讓我們依次介紹其中的每一個。

I think in the Cardiovascular segment, when you're trying to displace orals which have low compliance, certainly a twice-a-year injectable that can be used in a subcu setting very rapidly for patients who had previous heart attacks is very attractive to cardiologists and we think will lead to meaningful clinical benefit.

我認為在心血管領域，當你試圖取代依從性低的口服藥物時，一年兩次的注射劑可以非常迅速地用於以前心髒病發作的患者的 subcu 環境中，這對心髒病專家非常有吸引力我們認為這將帶來有意義的臨床益處。

Our expectation is in the rare disease setting, that while there is certainly -- it is certainly a barrier, to be clear, it is certainly a barrier that we have to overcome, that the current agents are used as infused medicines in the buy-and-bill setting, that in this population it's not a big enough driver of the economics that providing patients an oral option to avoid having to go in and out of the hospital could be highly appreciated, particularly given the opportunity to be front line and be used on top of the infused agents. So our expectation is, again, a lot of this does come to economics. And I think in that setting, the oral medicine has a very attractive profile.

我們的期望是在罕見病環境中，雖然肯定存在——這肯定是一個障礙，要明確的是，它肯定是我們必須克服的障礙，目前的藥物在購買中被用作輸注藥物——和賬單設置，在這個人群中，為患者提供口服選擇以避免進出醫院，這並不是一個足夠大的經濟驅動力，這可能會受到高度讚賞，特別是考慮到有機會成為前線並成為在註入的藥劑之上使用。所以我們的期望是，這其中很多確實會涉及到經濟學。而且我認為在這種情況下，口服藥物具有非常有吸引力的特徵。

And then I think in neuroscience, it is very clinic- and situation-specific. We certainly see the highest uptake in Kesimpta in segments of the market that are not highly penetrated by buy-and-bill. And I think in those segments of the market that have high utilization of buy-and-bill, there's less interest in using Kesimpta.

然後我認為在神經科學中，它是非常針對臨床和特定情況的。我們當然看到 Kesimpta 在購買和開票滲透率不高的細分市場中吸收率最高。而且我認為在那些使用買單的市場中，使用 Kesimpta 的興趣不大。

Luckily, in MS, the penetration of B-cell therapies is still relatively low given the efficacy of these B-cell therapies. So there is a vast market opportunity to displace the older agents, the braces, so to speak, and that is a big opportunity, and that's 60% of our source of business. And so we have ample opportunity there to get into the market and be successful.

幸運的是，鑑於這些 B 細胞療法的療效，在 MS 中，B 細胞療法的滲透率仍然相對較低。因此，可以說，有一個巨大的市場機會來取代舊代理，即牙套，這是一個巨大的機會，這是我們 60% 的業務來源。因此，我們有充足的機會進入市場並取得成功。

So you've got to look at the dynamics in each one. But certainly, in certain instances, buy-and-bill can be a formidable obstacle in our market environment. Next question operator.

所以你必須看看每一個的動態。但可以肯定的是，在某些情況下，買單可能是我們市場環境中的一個巨大障礙。下一個問題運算符。

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

您的下一個問題來自花旗銀行的 Andrew Baum。

Just following up from the last question, but staying within the cardiovascular domain. Amgen has a mRNA-based technology which is once every 6 months. It will be buy-and-bill. Thinking about how you are building out the buy-and-bill infrastructure, I'm just thinking about with -- I'm thinking about how that's going to fit in within that environment?

只是跟進上一個問題，但停留在心血管領域。安進有一項基於 mRNA 的技術，每 6 個月一次。這將是購買和賬單。考慮到您如何構建購買和計費基礎設施，我只是在考慮——我在考慮如何適應這種環境？

You mean for Lp(a), Andrew?

你是說Lp(a)，安德魯？

For Lp(a), yes, sorry if I said -- yes, sorry, I misspoke.

對於 Lp(a)，是的，對不起，如果我說 -- 是的，對不起，我說錯了。

Yes, absolutely. So of course, we're watching the Lp(a) evolution as well competitive environment. Certainly, it's an siRNA, which I understood is quarterly, I'll have to double check with my team if it's quarterly or bi-yearly, But certainly, that will be able to be used through the system. And as we think about life cycle managing Leqvio, our goal will be to, of course, also think about ways to continue to leverage the infrastructure that we're building.

是的，一點沒錯。所以當然，我們正在關注 Lp(a) 的演變以及競爭環境。當然，它是一種 siRNA，我知道是每季度一次，如果是每季度一次還是每兩年一次，我必須與我的團隊再次確認，但可以肯定的是，它可以通過系統使用。當我們考慮生命週期管理 Leqvio 時，我們的目標當然是考慮如何繼續利用我們正在構建的基礎設施。

To be clear, and I think that's your point, Andrew, I think our current Lp(a) pelacarsen medicine would not be able to leverage buy-and-bill. But again, the size of these markets are so large, we still think there will be a substantial market opportunity as the first-to-market subcu medicines for these patients. And then, of course, we will -- we are looking, of course, to get to less frequent dosing.

需要明確的是，我認為這就是你的觀點，安德魯，我認為我們目前的 Lp(a) pelacarsen 藥物將無法利用購買和賬單。但同樣，這些市場的規模如此之大，我們仍然認為作為這些患者的首個上市亞cu藥物將有很大的市場機會。然後，當然，我們會 - 當然，我們正在尋求減少給藥頻率。

We do think to be successful in cardiovascular buy-and-bill, you have to be relatively infrequent, even quarterly, we'll have to see. But certainly, twice a year is a winner, we think, in this market segment. Next question operator.

我們確實認為要在心血管購買和賬單方面取得成功，您必須相對不頻繁，甚至每季度一次，我們將不得不看到。但可以肯定的是，我們認為，在這個細分市場中，一年兩次是贏家。下一個問題運算符。

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。

It's on cell therapy. I wonder, firstly, Vas, if you could elaborate on the statement in the press release about lower demand for Kymriah. Is that simply the nature of cell therapies in general in this environment, whether there was anything specific to Kymriah?

這是細胞療法。首先，我想知道 Vas，您能否詳細說明新聞稿中關於 Kymriah 需求下降的聲明。在這種環境下，這僅僅是細胞療法的本質嗎？是否有任何特定於 Kymriah 的東西？

And related to that, I see last week, you pushed back the time lines for your genome-edited stem cell therapy for sickle cell from late '23 to August '25. I just wonder if you could give us any color on why that was.

與此相關，我上週看到，您將鐮狀細胞基因組編輯幹細胞療法的時間線從 23 年末推遲到 25 年 8 月。我只是想知道你是否可以告訴我們為什麼會這樣。

Yes. So on the second part of your question, I'd have to get back to you, Simon, I don't know offhand on the genome editing starts. We'll come back to you on that.

是的。所以關於你問題的第二部分，我必須回复你，西蒙，我不知道基因組編輯開始的時候。我們會在這方面回复您。

Look, I think on Kymriah, just to provide a very realistic perspective, the DLBCL second line, the failure of Kymriah in the second-line DLBCL is beginning to hit demand and I think we will see Kymriah to have less growth over the coming quarters and years and potentially even declines as our 2 competitors build out their second-line DLBCL program.

看，我認為關於 Kymriah，只是為了提供一個非常現實的觀點，DLBCL 二線，Kymriah 在二線 DLBCL 的失敗開始影響需求，我認為我們將看到 Kymriah 在未來幾個季度的增長放緩隨著我們的 2 個競爭對手建立他們的二線 DLBCL 計劃，甚至可能下降。

So realistically for us in cell therapies, of course, Kymriah has the -- is the only medicine indicated in pediatric ALL, has a broad label in later lines across DLBCL and FL, in the longer term, it really comes down to our next-generation T-Charge platform, which we provided data on at the end of last year at ASH, where we demonstrated pretty attractive data in both DLBCL and multiple myeloma.

當然，對於我們在細胞療法中的現實而言，Kymriah 有 - 是兒科 ALL 中唯一適用的藥物，在 DLBCL 和 FL 的後期線中有廣泛的標籤，從長遠來看，它真的歸結為我們的下一個 -一代 T-Charge 平台，我們在去年年底在 ASH 上提供了數據，在那裡我們展示了 DLBCL 和多發性骨髓瘤的非常有吸引力的數據。

And I think in the intervening years, it's really just managing Kymriah to provide it to patients to really focus on that next-wave technology. which we expect to have materially lower COGS, hopefully much higher throughput times, better efficacy and safety and enable the overall business to be significantly more attractive and more in line with other oncology agents in the company.

而且我認為在隨後的幾年中，實際上只是管理 Kymriah 為患者提供它，以真正專注於下一代技術。我們預計其 COGS 將大幅降低，希望有更高的生產時間、更好的療效和安全性，並使整體業務更具吸引力，並與公司的其他腫瘤藥物更加一致。

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

您的下一個問題來自 Cowen 的 Steve Scala。

Kisqali had its first appreciably down quarter, quarter-over-quarter since launch 5 years ago. You noted the weakness in new prescriptions, but even during the pandemic, Kisqali was, at worst, flat. I am wondering what other reasons there could be for the current weakness. It seems it could be deeper than simply new prescription trends.

自 5 年前推出以來，Kisqali 出現了第一個明顯下降的季度，環比下降。您注意到新處方的弱點，但即使在大流行期間，Kisqali 最壞的情況也是持平。我想知道目前的疲軟還有什麼其他原因。似乎它可能比簡單的新處方趨勢更深刻。

Yes. So we did have some stocking movements in the U.S. Harry, you want to say a word on Kisqali U.S., maybe that would help explain Steve's questions.

是的。所以我們在美國確實有一些放養運動。哈利，你想談談美國的 Kisqali，也許這有助於解釋史蒂夫的問題。

Yes. Thank you, Vas. So in the U.S., Steve, there was a slightly higher year-end stocking effects in the U.S. at the end of December. That has been worked through in quarter 1. Totally for the company, there was nothing significant. But -- so there was an effect on that -- and that was basically impacting the U.S. growth in the high single-digit percent point. So that's made a bit worse than what one would expect.

是的。謝謝你，瓦斯。所以在美國，史蒂夫，12 月底美國的年終庫存效應略高。這已經在第一季度完成了。對公司來說，沒有什麼重要的。但是——因此對此產生了影響——這基本上影響了美國高個位數百分點的增長。所以這比人們預期的要糟糕一些。

So -- but overall, of course, we see also we would -- we need to see more NBRx growth. There, we are just flat, if you will. But that was on a single-brand basis, not a small amount, if you will, that impacted, of course, quarter 1 -- this one quarter 1 last year comparison.

所以——但總的來說，當然，我們也看到我們會——我們需要看到更多的 NBRx 增長。在那裡，如果你願意的話，我們只是平坦的。但這是在單一品牌的基礎上，如果你願意的話，數量不小，這當然會影響第一季度——這是去年第一季度的比較。

And we would expect in quarter 2, still at least from where we sit today, to see a return to the historical profile of Kisqali growth. I think we have a few more questions, operator. Next question please.

我們預計在第二季度，至少從我們今天所處的位置來看，將看到 Kisqali 增長的歷史概況。我想我們還有幾個問題，接線員。請下一個問題。

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

您的下一個問題來自瑞士信貸的 Matthew Weston。

Vas, I promise it's my last. It's on (inaudible). And if you could just give us an update. Obviously, COVID is waning hopefully or certainly in everyone's hopes, but we're still seeing government is making very significant purchases to stockpile various treatment agents. So can you tell us where you are in terms of your expectations for the molecule, but specifically your plans for the subcu trial and whether or not we should expect that to start in the near future.

瓦斯，我保證這是我的最後一次。開啟（聽不清）。如果你能給我們一個更新。顯然，COVID 希望或肯定在每個人的希望中都在減弱，但我們仍然看到政府正在大量購買以儲存各種治療劑。那麼你能告訴我們你對分子的期望在哪裡，特別是你對 subcu 試驗的計劃，以及我們是否應該期望它在不久的將來開始。

Yes. Thanks, Matthew. As we note actually in one of the slides, we filed the EUA, and the EUA remains open with the FDA. However, at this point, given the latest feedback that in our discussions with the agency, we would expect the agency to require a Phase III study before granting an EUA approval or a general approval. We're in discussions now to understand the final study design and what the agency would expect. And then we need to make a kind of sober evaluation as to is it a doable study in light of the waning rates of COVID around the world and then we can make an appropriate decision.

是的。謝謝，馬修。正如我們在其中一張幻燈片中實際指出的那樣，我們提交了 EUA，而 EUA 仍然對 FDA 開放。然而，在這一點上，鑑於我們與該機構討論的最新反饋，我們預計該機構在授予 EUA 批准或一般批准之前需要進行 III 期研究。我們現在正在討論以了解最終的研究設計以及該機構的期望。然後我們需要做出一種清醒的評估，根據全球新冠病毒感染率的下降，這是否是一項可行的研究，然後我們才能做出適當的決定。

Certainly, we believe in the profile of the molecule and certainly our discussions with the U.S. government, they're excited about the concept of a onetime subcu therapy.

當然，我們相信分子的概況，當然也相信我們與美國政府的討論，他們對一次性 subcu 療法的概念感到興奮。

Alongside that, we do have a once-a-day oral agent that is currently completing the various preclinical tox in early studies. We should have a read on whether it's developable over the summer. And then we have to have a similar conversation. It's an MPro inhibitor. And we have to have a similar conversation with FDA as to what would be the clinical development requirements. And again, in the context, is it developable and how long would it take to just accrue the events required. Last question operator. I think it's Graham. Graham?

除此之外，我們確實有一種每天一次的口服藥物，目前正在完成早期研究中的各種臨床前毒性。我們應該閱讀一下它是否可以在夏天開發。然後我們必須進行類似的對話。它是一種 MPro 抑製劑。我們必須與 FDA 就臨床開發要求進行類似的對話。同樣，在上下文中，它是否可開發，以及僅累積所需事件需要多長時間。最後一個問題運算符。我認為是格雷厄姆。格雷厄姆？

Graham Parry, Bank of America.

美國銀行格雷厄姆·帕里。

Great. I'll go for round 3. So just first of all, just a quick follow-up to the first question I asked on NATALEE. I just wondered, as you're slipping into 2023, is it just slipping into 2023 or on the event rate that you're looking at, at the moment, is it a first half or second half '23 read?

偉大的。我將參加第 3 輪。所以首先，快速跟進我在 NATALEE 上提出的第一個問題。我只是想知道，當您滑入 2023 年時，它只是滑入 2023 年還是您正在查看的事件率，目前，它是 23 年上半年還是下半年？

And then on Cosentyx is my actual follow-up. You've got the initial plan of Phase II date, I think, this year. It's a large indication, lots of patients. I just wondered if you are thinking about this as a longer-term opportunity. Because on your IP slide, it says Cosentyx passes 2029 plus. I'm wondering, are you looking at additional IP protection strategies for Cosentyx beyond 2029?

然後在 Cosentyx 上是我的實際跟進。我想，今年你已經有了第二階段日期的初步計劃。這是一個很大的跡象，很多病人。我只是想知道你是否認為這是一個長期的機會。因為在你的 IP 幻燈片上，它說 Cosentyx 通過 2029 plus。我想知道，您是否正在考慮 Cosentyx 2029 年以後的其他知識產權保護策略？

Yes. Thanks, Graham. On NATALEE, nothing more I can really say at this point. I think we'll continue to update the event rates and provide more granularity on when we would expect a final readout over the course of this year. But I think we give you the best forecast we have now that it's now pushed into 2023.

是的。謝謝，格雷厄姆。關於 NATALEE，此時我真的無話可說。我認為我們將繼續更新事件發生率，並提供更詳細的信息，說明我們預計在今年的最終讀數的時間。但我認為我們給了你最好的預測，因為它現在被推到了 2023 年。

On Cosentyx, we do have like (inaudible) readout upcoming. And we are looking at, of course, the standard patent extension strategy beyond 2029, also currently to continuing to progress in NIBR efforts to develop an oral IL-17 inhibitor as well as other life cycle management strategies, biologic strategies for Cosentyx. Nothing concrete as of yet but certainly high on our mind to get Cosentyx to move into the 2030 alongside continuing to defend the full patent state of Entresto. We have 10 Orange Book patents now issued and our goal continues to be to defend that, to see how -- to try to keep Entresto protected for as long as possible as well.

在 Cosentyx 上，我們確實有類似（聽不清）的讀數即將發布。當然，我們正在研究 2029 年之後的標準專利延期策略，目前也在繼續推進 NIBR 努力開發口服 IL-17 抑製劑以及其他生命週期管理策略，Cosentyx 的生物策略。目前還沒有什麼具體的東西，但我們肯定很想讓 Cosentyx 進入 2030 年，同時繼續捍衛 Entresto 的完整專利狀態。我們現在已經發布了 10 項橙皮書專利，我們的目標仍然是捍衛這一點，看看如何——盡可能長時間地保護 Entresto。

So thank you, everyone, for the call. I really appreciate it. Great questions from everyone. We'll look forward to speaking to everybody soon. Thank you again for your interest in Novartis.

所以，謝謝大家的來電。對此，我真的非常感激。每個人都提出了很好的問題。我們期待很快與大家交談。再次感謝您對諾華的關注。

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

謝謝你。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。