Novartis AG (NVS) 2023 Q1 法說會逐字稿

Good morning and good afternoon, and welcome to the Novartis Q1 2023 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.

早上好，下午好，歡迎來到諾華 2023 年第一季度業績發布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。

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

就此，我想請投資者關係全球主管 Samir Shah 先生髮言。請繼續，先生。

Thank you very much, and good morning and good afternoon, everybody. Thank you once again for all the participants on the call and the webcast for taking the time to listen to our quarterly conference call.

非常感謝，大家早上好，下午好。再次感謝電話和網絡廣播中的所有參與者抽出時間收聽我們的季度電話會議。

Before I start, just a safe harbor statement. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements.

在我開始之前，只是一個安全港聲明。今天提供的信息包含前瞻性陳述，涉及已知和未知的風險、不確定性和其他因素。這些可能導致實際結果與此類陳述明示或暗示的任何未來結果、業績或成就存在重大差異。

For a description of some of these factors, please refer to the company's Form 20-F, its most recent quarterly results on Form 6-K that respectively were filed with and furnished to the U.S. Securities and Exchange Commission.

有關其中一些因素的說明，請參閱公司的 20-F 表格，以及分別向美國證券交易委員會備案和提供的 6-K 表格的最新季度業績。

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

然後，我將交給 Vas。

Thank you, Samir, and thanks everyone for joining today's call. If we move to Slide 4, Novartis delivered a strong first quarter to start the year. We had strong sales growth, robust margin expansion. We hit our key innovation milestones and we're raising our full year 2023 guidance, which Harry will go through in more detail.

謝謝 Samir，也感謝大家參加今天的電話會議。如果我們轉到幻燈片 4，諾華公司在今年年初的第一季度表現強勁。我們有強勁的銷售增長，強勁的利潤增長。我們達到了關鍵的創新里程碑，我們正在提高 2023 年全年的指導方針，Harry 將對此進行更詳細的介紹。

As you saw in this morning's press release, sales were up 8%. Core operating income was up 15% in constant currencies. In Innovative Medicines, sales were up 7%, and core operating income was up 18%, we achieved a core margin of 38.7% in IM, and Sandoz was up 8% with core operating income up 3%. I'll go through some of the innovation milestones in the subsequent slides as well as an update on our recent approvals of our Millburn and Zaragoza manufacturing facilities.

正如您在今天上午的新聞稿中看到的那樣，銷售額增長了 8%。按固定匯率計算，核心營業收入增長了 15%。在創新藥物方面，銷售額增長了 7%，核心營業收入增長了 18%，我們在 IM 中實現了 38.7% 的核心利潤率，Sandoz 增長了 8%，核心營業收入增長了 3%。我將在隨後的幻燈片中介紹一些創新里程碑，以及我們最近批准我們的 Millburn 和 Zaragoza 製造設施的最新情況。

Now moving to Slide 5. Our key 2023 readouts for our upcoming high-value medicines remain on track. You surely saw earlier in the quarter, our Phase III NATALEE trial in adjuvant breast cancer testing this medicine in a broad patient population and had it met primary endpoint at its second interim analysis. Pluvicto is continues to stay on track with the PSMA 4 trial in metastatic castration-resistant prostate cancer having a positive top line readout, we expect to achieve the OS endpoints over the course of the summer with a detailed data presentation in the second half of the year and plan for regulatory submissions in the second half of 2023.

現在轉到幻燈片 5。我們對即將推出的高價值藥物的 2023 年關鍵讀數仍在進行中。您肯定在本季度早些時候看到，我們在輔助乳腺癌中進行的 III 期 NATALEE 試驗在廣泛的患者群體中測試了該藥物，並在第二次中期分析中達到了主要終點。 Pluvicto 繼續保持在轉移性去勢抵抗性前列腺癌的 PSMA 4 試驗的正軌上，該試驗具有積極的頂線讀數，我們預計在夏季的過程中實現 OS 終點，並在下半年提供詳細的數據2023 年下半年提交監管文件的年度和計劃。

And iptacopan continues to stay on track as well. Tomorrow, we will read out the data from the APPOINT-PNH trial in treatment-naive patients. I'll speak more about that in a moment. and we're on track with both the IgAN and C3G readouts.

iptacopan 也繼續保持在正軌上。明天，我們將宣讀在初治患者中進行的 APPOINT-PNH 試驗的數據。稍後我會詳細說明這一點。我們正在跟踪 IgAN 和 C3G 讀數。

Now moving to Slide 6. Our submission-enabling readouts are expected to increase in the '24 and '25 time frame with a number of, we think, potentially exciting assets if the data continues to hold. Remibrutinib will achieve its primary analysis in CSU for efficacy in the second half of 2023, and the final analysis, which would include additional safety follow-up alongside potential submission in 2024. We've accelerated our assemblies timing in first-line CML with a readout and submission now expected in 2024. Also of note, we remain on track with our SMA IT readout for OAV-101 for 2024 and I also wanted to highlight that ianalumab across a broad range of indications has began -- begun Phase III clinical starts, including in first and second-line ITP as well as in SLE and lupus nephritis.

現在轉到幻燈片 6。我們認為，如果數據繼續保持下去，我們認為支持提交的讀數將在 24 和 25 年的時間範圍內增加，我們認為，這些資產可能會令人興奮。 Remibrutinib 將於 2023 年下半年在 CSU 完成初步療效分析，最終分析將包括額外的安全跟進以及 2024 年的潛在提交。我們已經加快了一線 CML 的組裝時間現在預計在 2024 年進行讀出和提交。另外值得注意的是，我們仍在按計劃進行 2024 年 OAV-101 的 SMA IT 讀出，我還想強調指出，ianalumab 已經開始廣泛適應症——開始 III 期臨床，包括一線和二線 ITP 以及 SLE 和狼瘡性腎炎。

Now moving to the next slide, Slide 7 and turning to a little bit more detail on some of these innovation highlights. The NATALEE study met its primary endpoint, demonstrating clinically meaningful IDSS in a broad early breast cancer population. This study looked at Kisqali plus endocrine therapy with a 400-milligram dose and it significantly reduced the risk of disease recurrence for standard endocrine therapy alone. The benefit was consistent in a broad population of stage II and III early best breast cancer patients -- we expect to present this data at an upcoming medical meeting, and we're on track for worldwide regulatory submissions in the second half of 2023.

現在轉到下一張幻燈片，即幻燈片 7，並詳細介紹其中一些創新亮點。 NATALEE 研究達到了其主要終點，在廣泛的早期乳腺癌人群中證明了具有臨床意義的 IDSS。這項研究考察了 Kisqali 加上 400 毫克劑量的內分泌治療，它顯著降低了單獨使用標準內分泌治療的疾病復發風險。該益處在廣泛的 II 期和 III 期早期最佳乳腺癌患者群體中是一致的——我們希望在即將召開的醫學會議上展示這些數據，並且我們有望在 2023 年下半年提交全球監管文件。

As a reminder, 30% to 60% of patients with Stage II and III early breast cancer treated with endocrine therapy alone remain at risk of breast cancer recurrence. And I also wanted to highlight that our 400-milligram dose was used specifically to reduce dose-dependent AEs given the importance of a good tolerability profile in treating early breast cancer.

提醒一下，僅接受內分泌治療的 II 期和 III 期早期乳腺癌患者中有 30% 至 60% 仍有乳腺癌復發的風險。我還想強調，鑑於良好的耐受性在治療早期乳腺癌中的重要性，我們的 400 毫克劑量專門用於減少劑量依賴性 AE。

Now moving to Slide 8. I wanted to get into a little bit more detail on the patient population addressed by the Kisqali NATALEE study. We've previously guided that this is a multibillion-dollar opportunity for Kisqali in addition to the multibillion-dollar opportunity we have in the metastatic setting. You can see here on the left-hand side of the slide, the incidents that we now estimate based on updated data sets that we've been able to identify, the NATALEE population covers 70% of Stage 2 and 100% of Stage 3 patients, and it's approximately 2 to 3x the size of the competitor study.

現在轉到幻燈片 8。我想更詳細地了解 Kisqali NATALEE 研究針對的患者群體。我們之前曾指導過，除了我們在轉移性環境中擁有的數十億美元機會之外，這對 Kisqali 來說也是一個數十億美元的機會。您可以在幻燈片的左側看到，我們現在根據我們能夠識別的更新數據集估計的事件，NATALEE 人群覆蓋了 70% 的第 2 階段患者和 100% 的第 3 階段患者，大約是競爭對手研究規模的 2 到 3 倍。

You can see the profile in a bit more detail on the right-hand side of the slide. You can see that in the Stage 2 population, we have unique tonally and a total population across the Stage 3 as well that's unique to NATALEE. So it gives you a good sense of the comparison across the NATALEE and MonarchE profiles.

您可以在幻燈片的右側更詳細地查看配置文件。您可以看到，在第 2 階段人口中，我們擁有獨特的音調和整個第 3 階段的總人口，這也是 NATALEE 所獨有的。因此，它可以讓您很好地了解 NATALEE 和 MonarchE 配置文件之間的比較。

Now moving to Slide 9 and turning to iptacopan. Our APPOINT-PNH data showed clinically meaningful increases in hemoglobin, and we top lined this data in the quarter 4 of last year. This was a single arm Phase III study in adult patients with PNH with hemolysis and anemia. They were naive to complement inhibitors and complements the already -- the data we've already demonstrated in patients who were not adequately controlled by C5 inhibitors. The study met its primary endpoint had a strong safety profile. And as I already mentioned, the data will be presented tomorrow, and we look forward to using that data alongside our already completed previous trials as part of our regulatory package. We have completed the submission of iptacopan in the U.S., and we are awaiting regulatory acceptance, which we hope will happen soon.

現在轉到幻燈片 9 並轉向 iptacopan。我們的 APPOINT-PNH 數據顯示血紅蛋白有臨床意義的增加，我們在去年第 4 季度將這一數據排在首位。這是一項針對伴有溶血和貧血的 PNH 成年患者的單臂 III 期研究。他們天真地補充抑製劑和補充已經 - 我們已經在 C5 抑製劑沒有充分控制的患者中證明的數據。該研究達到了其主要終點，具有很強的安全性。正如我已經提到的，數據將於明天公佈，我們期待將這些數據與我們已經完成的先前試驗一起用作我們監管方案的一部分。我們已經在美國完成了 iptacopan 的提交，我們正在等待監管機構的接受，我們希望這會很快發生。

Now moving to Slide 10. We strengthened our radioligand therapy pipeline with multiple deals over the course of the quarter. Some of the recent business development activities included a discovery collaboration with Bicycle Therapeutics, which employs cyclic peptides and that allows us to target additional interesting targets from a radioligand therapy perspective and it supplements our existing discovery platform.

現在轉到幻燈片 10。我們在本季度通過多項交易加強了我們的放射配體治療管道。最近的一些業務發展活動包括與 Bicycle Therapeutics 的發現合作，它使用環肽，使我們能夠從放射配體治療的角度瞄準更多有趣的目標，並補充我們現有的發現平台。

In addition, we completed an acquisition of FAP-2286 from Clovis Oncology, which is a fibroblast activation protein, and we believe it represents a promising RLT target in a range of solid tumors you see listed here. The asset is in Phase I/II development, it's shown for signs of efficacy. And it complements the growing clinical stage pipeline we have outlined on the right-hand side of the slide, which includes taking Lutathera into multiple different solid tumors, the continued expansion of Pluvicto, as I've already outlined, as well as the progress we're making on NeoB and now the acquisition of FAP-2286. So we look forward to keeping you updated as we continue to progress our radioligand therapy portfolio.

此外，我們完成了對 Clovis Oncology 的 FAP-2286 的收購，這是一種成纖維細胞活化蛋白，我們相信它代表了您在此處看到的一系列實體瘤中有前途的 RLT 靶點。該資產處於 I/II 期開發階段，已顯示出療效跡象。它補充了我們在幻燈片右側概述的不斷增長的臨床階段管道，其中包括將 Lutathera 用於多種不同的實體瘤、Pluvicto 的持續擴張，正如我已經概述的那樣，以及我們取得的進展正在製作 NeoB，現在收購 FAP-2286。因此，隨著我們繼續推進我們的放射配體治療產品組合，我們期待著讓您了解最新情況。

Now moving to Slide 11 and turning to our growth in the quarter and growth drivers. Our key growth drivers delivered 67% growth in constant currencies, and we expect that growth to continue. This growth was highlighted by performance from Entresto, Pluvicto, Kesimpta and Kisqali.

現在轉到幻燈片 11 並轉向我們在本季度的增長和增長動力。我們的主要增長動力以固定匯率計算實現了 67% 的增長，我們預計這種增長將繼續下去。 Entresto、Pluvicto、Kesimpta 和 Kisqali 的業績突顯了這一增長。

Now turning to these brands, each one in turn on Slide 12. Entresto delivered strong double-digit growth across geographies. You can see a growth rate of 32% with growth across ex U.S. and U.S. a strong weekly TRx trend, which is continuing the trend we've seen now for multiple years with this medicine. The momentum is outpacing the market with the U.S. NBRx now up 30%, we continue to see growth in the EU with HFrEF patients. And importantly, in China and Japan, we're not only seeing expansion in heart failure patients, but also a significant contribution from our indications in these geographies in hypertension.

現在轉向這些品牌，每個品牌依次出現在幻燈片 12 上。Entresto 在各個地區實現了強勁的兩位數增長。你可以看到 32% 的增長率，除美國外和美國都有強勁的每週 TRx 趨勢，這延續了我們多年來使用這種藥物所看到的趨勢。這一勢頭超過了市場，美國 NBRx 現在上漲了 30%，我們繼續看到歐盟 HFrEF 患者的增長。重要的是，在中國和日本，我們不僅看到心力衰竭患者的增加，而且我們在這些地區的高血壓適應症也做出了重大貢獻。

We remain confident in the future growth profile. We expect further penetration across half breast robust guideline positions to support our overall growth. And importantly, we received CHMP positive opinion for pediatric heart failure, which, if ultimately approved by the European Commission, will extend the loss of exclusivity in the EU until the end of 2026.

我們對未來的增長前景充滿信心。我們預計將進一步滲透到半乳穩健的指導位置，以支持我們的整體增長。重要的是，我們收到了 CHMP 對兒科心力衰竭的積極意見，如果最終獲得歐盟委員會的批准，將把歐盟的獨占權喪失期限延長至 2026 年底。

Now moving to the next slide, Slide 13. Cosentyx ex U.S. growth offset our U.S. declines. And as we've guided to, we continue to believe that global full year sales will be broadly in line with the prior year. Getting into a little bit more on these dynamics. In the U.S., we saw demand growth, which was solid, offset by revenue deductions, about half of the decline that we saw was due to prior year base effects where the revenue deductions that we disclosed in quarter 4 were not in Q1 of last year.

現在轉到下一張幻燈片，幻燈片 13。Cosentyx 在美國以外的增長抵消了我們在美國的下滑。正如我們所指導的那樣，我們仍然相信全球全年銷售額將與上一年大致持平。深入了解這些動態。在美國，我們看到需求增長穩健，被收入扣除所抵消，我們看到的下降中約有一半是由於去年的基數效應，我們在第四季度披露的收入扣除不在去年第一季度.

In addition, we did have some inventory movements. So overall, we do see in the U.S. approximately a high sum-single-digit decline in Cosentyx performance, which is in line with what our expectations were. Ex U.S., we see strong growth in our core indications. Importantly, in China, we're outperforming the market with our NRDL listing with Cosentyx double-digit growth now post COVID.

此外，我們確實有一些庫存變動。因此，總的來說，我們確實看到 Cosentyx 在美國的表現出現了大約一個位數的高額下滑，這符合我們的預期。除美國外，我們看到核心適應症出現強勁增長。重要的是，在中國，我們的 NRDL 上市表現優於市場，Cosentyx 現在在 COVID 後實現兩位數增長。

As I mentioned, we expect our sales to be broadly in line, and our future growth will be driven by life cycle management. We have the CHMP opinion for hidradenitis expected in quarter 2, we're expecting approvals in the U.S. for both hidradenitis and our IV formulation in the second half, we're on track with our lupus nephritis and GCA studies, and we've initiated 2 additional studies in Polymyalgia Rheumatica and Rotator cuff tendinopathy.

正如我所提到的，我們預計我們的銷售額將大致保持一致，我們未來的增長將由生命週期管理驅動。我們預計在第二季度獲得 CHMP 對汗腺炎的意見，我們預計下半年在美國批准汗腺炎和我們的 IV 製劑，我們正在進行狼瘡性腎炎和 GCA 研究，並且我們已經啟動2 項關於風濕性多肌痛和肩袖肌腱病的額外研究。

Moving to Slide 14, just to highlight some of the data we released in Cosentyx in the quarter. In hidradenitis, we had demonstrated durable efficacy sustained up to 1 year. This is a disease that's characterized by lesions and abscesses, patients really suffer from the disease. So really, what is critical is that we can address pain and address some of the more problematic manifestations of the disease. On the right-hand side, our data demonstrate durable efficacy, which is sustained out to 1 year across the various patient populations, greater than 70% of patients were flare fee, greater than 65% had solid pain control. And we saw a fast and lasting quality of life improvement.

轉到幻燈片 14，只是為了突出我們本季度在 Cosentyx 中發布的一些數據。在汗腺炎中，我們已經證明了持續長達 1 年的持久療效。這是一種以病變和膿腫為特徵的疾病，患者確實患有這種疾病。所以說真的，關鍵是我們可以解決疼痛并解決該疾病的一些更有問題的表現。在右側，我們的數據證明了持久的療效，在不同的患者群體中持續長達 1 年，超過 70% 的患者出現耀斑，超過 65% 的患者疼痛得到有效控制。我們看到了快速而持久的生活質量改善。

So taken together, we think the medicine is well positioned in what could be a sizable market as more and more therapies become available to treat these patients with the biologics that they likely need.

因此，綜上所述，我們認為隨著越來越多的療法可用於治療這些患者可能需要的生物製劑，該藥物在一個可能相當大的市場中處於有利地位。

Now moving to the next slide, Slide 15. Kesimpta continued its strong launch trajectory, doubling sales versus prior year. You can see the 100% growth on the chart, this was driven by strong TRx growth were up 89% versus prior year, strong NBRx growth were up 60% versus prior year. Importantly, the B-cell NBRx show that we -- is currently about 50% of the MS market. So there continues to be room for further B-cell expansion.

現在轉到下一張幻燈片，即幻燈片 15。Kesimpta 繼續其強勁的發布軌跡，銷售額比上一年翻了一番。您可以在圖表上看到 100% 的增長，這是由 TRx 的強勁增長推動的，與去年相比增長了 89%，NBRx 的增長與去年相比增長了 60%。重要的是，B 細胞 NBRx 表明我們目前約佔 MS 市場的 50%。因此，B 細胞的進一步擴增仍有空間。

In Europe, there was strong launch momentum as well with now 65% of the population with access to Kesimpta. We're confident in the continued growth of this medicine. We think there's significant room to grow the B-cell market share in the U.S. And we also have a compelling product profile, 1 minute a month dosing from home or anywhere strong 5-year efficacy and safety data. So we'll continue to drive strong performance with Kesimpta over the course of this year.

在歐洲，也有強勁的啟動勢頭，現在有 65% 的人口可以使用 Kesimpta。我們對這種藥物的持續增長充滿信心。我們認為美國的 B 細胞市場份額有很大的增長空間，而且我們也有引人注目的產品概況，每月 1 分鐘在家或任何地方給藥，5 年療效和安全性數據強勁。因此，我們將在今年繼續推動 Kesimpta 的強勁表現。

Now you likely saw on Slide 16 that Kisqali had an outstanding quarter, and we're gaining momentum globally with increasing recognition of its differentiated profile supported by strong Phase III outcomes data. You see a growth of 81% on the sales line are metastatic breast cancer market share. NBRx share is now at 28% in the U.S. In the EU 5, our NBRx share is up to now 38%. We have the favorable NCCN guidelines as the only Category 1 treatment for first-line metastatic breast cancer with an aromatase inhibitor and the positive readout as we've already discussed for the Phase III NATALEE study. So we expect continued momentum for Kisqali as it achieved its multibillion-dollar potential in the metastatic setting.

現在你可能在幻燈片 16 上看到 Kisqali 有一個出色的季度，我們正在全球範圍內獲得動力，越來越多的人認識到它在強大的 III 期結果數據的支持下的差異化形象。你看到銷售線上 81% 的增長是轉移性乳腺癌的市場份額。 NBRx 在美國的份額目前為 28%。在歐盟 5 國，我們的 NBRx 份額目前高達 38%。我們擁有有利的 NCCN 指南，這是唯一一種使用芳香化酶抑製劑治療轉移性乳腺癌的第一類藥物，並且正如我們已經在 III 期 NATALEE 研究中討論過的那樣，結果是積極的。因此，我們預計 Kisqali 將繼續保持增長勢頭，因為它在轉移性環境中實現了數十億美元的潛力。

Now moving to Slide 17, with Leqvio, our adoption is continuing to expand as we steadily progress this launch. What we wanted to highlight here is when you look at adoption, the number of facilities that are now ordering Leqvio, we're up to 2,200 facilities. Our number of physicians that have experience now with Leqvio is up to 9,600 and our focus now is to drive greater depth in these accounts as these accounts get more comfortable with buy and bill, which will absolutely be critical for the long-term success of this product.

現在轉到幻燈片 17，隨著 Leqvio 的穩步推進，我們的採用率將繼續擴大。我們想在這裡強調的是，當您查看採用情況時，現在訂購 Leqvio 的設施數量多達 2,200 家。我們現在擁有 Leqvio 經驗的醫生人數高達 9,600 人，我們現在的重點是進一步深入這些客戶，因為這些客戶對購買和賬單更加滿意，這對於長期成功絕對至關重要產品。

Our access rate is at 76% adherence now to the second dose within 95 days to 75%. So the foundations are getting put in place for this medicine, and we continue to track well against the Entresto launch curve, which I think is -- gives you an indication of how we expect the launch to progress in the U.S. Globally, we're also seeing now the beginning of an acceleration as we continue to expand in Europe, and also wait for further acceleration in the U.K. with the NHS national program.

我們的訪問率是 76%，現在在 95 天內對第二劑的依從性達到 75%。因此，這種藥物的基礎已經到位，我們將繼續很好地跟踪 Entresto 的發射曲線，我認為這表明我們預計該藥物在美國的發射進展如何。在全球範圍內，我們隨著我們繼續在歐洲擴張，現在也看到了加速的開始，同時也在等待英國 NHS 國家計劃的進一步加速。

Now turning to Slide 18. Pluvicto is continuing to see outstanding demand and a strong benefit driven by a strong run of benefit risk profile and the unmet need in the post-taxane metastatic castrate-resistant prostate cancer setting. You saw the sales evolution now up to $211 million on the quarter. We do expect Q2 sales to be broadly in line with Q1 as we continue to ramp up the Millburn and Zaragoza facilities. We have 200 unique accounts, but importantly, have over 100 additional accounts were prepared to add on as supply continues to ramp, moving towards our goal to estimated 500 accounts in the U.S. as we move into broader and broader settings.

現在轉到幻燈片 18。Pluvicto 繼續看到巨大的需求和強大的收益，這是由強大的收益風險狀況和紫杉烷後轉移性去勢抵抗性前列腺癌環境中未滿足的需求驅動的。你看到本季度的銷售額現在高達 2.11 億美元。隨著我們繼續擴大 Millburn 和 Zaragoza 設施，我們確實預計第二季度的銷售額將與第一季度大致持平。我們有 200 個獨特的賬戶，但重要的是，隨著供應量的持續增加，我們準備增加 100 多個額外賬戶，隨著我們進入越來越廣泛的環境，朝著我們估計在美國擁有 500 個賬戶的目標邁進。

Our FDA submission for PSMAfore, including the OS data is on track, as I previously mentioned, and to get into a little bit more detail on the supply, turning to Slide 19. As you saw in our announcement last week, Millburn is approved for Pluvicto commercial supply in the U.S., and we already have started production in this facility. We also have Zaragoza approved in the EU, and we expect that facility to start producing for EU patients over the course of the coming weeks.

正如我之前提到的，我們向 FDA 提交的 PSMAfore（包括 OS 數據）正在按計劃進行，並且要更詳細地了解供應情況，請轉到幻燈片 19。正如您在我們上週的公告中看到的那樣，Millburn 被批准用於Pluvicto 在美國的商業供應，我們已經開始在這個工廠生產。我們還在歐盟批准了 Zaragoza，我們預計該設施將在未來幾週內開始為歐盟患者生產。

As we continue to add additional lines and bring additional lines operational in Millburn over the course of the coming months, we will expect to see in the second half of the year, a significant expansion in capacity, which will allow us to accelerate the launch as we move into the end of 2024 and 2025. Importantly, our Indianapolis facility as well as now in preparation for FDA filing, we hope to have that facility approved before the end of this year. And the last element of our story on production is the building of automated production lines, which allowed substantial capacity. We continue to target a capacity of at least 250,000 doses in 2024.

隨著我們在接下來的幾個月中繼續增加更多的線路並在 Millburn 運營更多的線路，我們預計將在今年下半年看到產能的顯著擴張，這將使我們能夠加速啟動，因為我們將進入 2024 年底和 2025 年底。重要的是，我們的印第安納波利斯工廠以及現在正在準備 FDA 備案，我們希望該工廠在今年年底前獲得批准。我們關於生產的故事的最後一個要素是自動化生產線的建設，這允許大量產能。我們的目標是在 2024 年至少達到 250,000 劑的產能。

Now lastly, turning to Scemblix. Scemblix continues to do well in the third-line setting for CML. Q1 sales were $76 million. Our global rollout is ongoing with approval in 46 countries. We have access pathways in 19. And I think there's a strong recognition of the efficacy and tolerability benefit of this medicine, and that's indicated by the rapid enrollment of the (inaudible) study with completed enrollment ahead of plan with a readout and filing now expected in 2024. So a strong start to the year, a strong first quarter.

最後，轉向 Scemblix。 Scemblix 在 CML 的三線環境中繼續表現出色。第一季度銷售額為 7600 萬美元。我們的全球推廣正在進行中，並在 46 個國家/地區獲得批准。我們在 19 年有了訪問途徑。而且我認為人們對這種藥物的療效和耐受性的好處有很強的認識，這通過（聽不清）研究的快速註冊表明了這一點，該研究提前完成了計劃的註冊，現在預計將進行讀出和歸檔2024 年。今年開局強勁，第一季度表現強勁。

And to give you more perspective on the financial performance in Q1, I'll hand it over to Harry. Harry?

為了讓您對第一季度的財務表現有更多的了解，我將把它交給哈利。哈利？

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

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數據。和往常一樣，除非另有說明，否則我的評論指的是固定匯率的增長率。正如您將從數字中看到的那樣，今年確實是一個非常強勁的開端。

Now on Slide 23. We detailed the strength of the top and bottom line performance during the quarter. Overall, we really have excellent business momentum, and our efforts to focus and streamline the business are starting to pay off on both the top and the bottom line. Sales grew 8%, benefiting from the strong performance of our in-market brands, in particular, Entresto, Pluvicto, Kesimpta, Kisqali, as Vas already laid out.

現在在幻燈片 23 上。我們詳細介紹了本季度頂線和底線表現的實力。總的來說，我們的業務發展勢頭非常好，我們集中精力和精簡業務的努力開始在收入和利潤方面得到回報。銷售額增長了 8%，這得益於我們市場品牌的強勁表現，尤其是 Vas 已經佈局的 Entresto、Pluvicto、Kesimpta、Kisqali。

Core operating income growth was up 15%, driven mainly by higher sales and core EPS even grew 25% to $1.71, faster than core operating income, benefiting from a lower weighted average number of shares outstanding. Free cash flow was [2.7] billion, growing 95%, mainly driven by higher income, favorable changes in working capital and some onetime legal matter. In summary, as I said, a very strong start to the year.

核心營業收入增長 15%，主要受銷售額增加的推動，核心每股收益甚至增長 25% 至 1.71 美元，快於核心營業收入，這得益於較低的已發行股票加權平均數。自由現金流為 [27] 億，增長 95%，主要受收入增加、營運資本的有利變化和一些一次性法律事務的推動。總之，正如我所說，今年開局非常強勁。

Next slide, please. Details here due to the performance of Innovative Medicines and Sandoz. Overall, the picture is quite cream above the board. And on the back of the strong sales performance of our growth drivers, IM sales grew 7%, which drove an increase in IM core operating income of 18% and the core margin reached 38.7%, up, I would say, an impressive 360 basis points increase versus prior year.

請換下一張幻燈片。由於 Innovative Medicines 和 Sandoz 的表現，此處提供了詳細信息。總的來說，這幅畫非常漂亮。在我們增長動力強勁的銷售業績的支持下，IM 銷售額增長了 7%，這推動 IM 核心營業收入增長了 18%，核心利潤率達到了 38.7%，我想說，360 度基礎上的增長令人印象深刻點比上年增加。

Sandoz net sales grew 8% this quarter, mainly driven by Europe, which benefited from continued momentum of prior year launches and a very strong cough and cold season. Sandoz core op inc was up 3% lower than sales, mainly due to some prior year divestment income and Sandoz core margin was 21%.

山德士本季度淨銷售額增長 8%，主要受歐洲推動，歐洲受益於去年推出產品的持續勢頭以及非常強勁的咳嗽和感冒季節。 Sandoz core op inc 比銷售額增長了 3%，這主要是由於前一年的一些撤資收入和 Sandoz 核心利潤率為 21%。

Next slide, please. The strong start of the year and confidence in our future growth allows us to raise both top and bottom line guidance for the full year of 2023. As you recall, we usually don't do that in quarter 1, but we really do have good momentum, and we don't think that will change as we go forward. For Innovative Medicines and Novartis excluding Sandoz, we now expect sales to grow mid-single digit and core operating income to grow high single to low double digits.

請換下一張幻燈片。今年的強勁開局和對我們未來增長的信心使我們能夠提高 2023 年全年的頂線和底線指導。您還記得，我們通常不會在第一季度這樣做，但我們確實有很好的勢頭，我們認為這不會隨著我們的前進而改變。對於 Innovative Medicines 和 Novartis（不包括 Sandoz），我們現在預計銷售額將增長中個位數，核心營業收入將增長高個位數到低兩位數。

For Novartis, including Sandoz, which is based on the group guidance and assuming for the forecasting numbers that Sandoz would remain within the group for the entire full year of 2023, we now expect sales to grow mid-single digit and core operating income to grow high single digit. Our key assumption is that no Sandoz [generics] would enter in the U.S. in 2023.

對於 Novartis，包括 Sandoz，它基於集團指導並假設 Sandoz 將在 2023 年全年留在集團內的預測數字，我們現在預計銷售額將增長中個位數，核心營業收入將增長高個位數。我們的關鍵假設是 Sandoz [仿製藥] 不會在 2023 年進入美國。

As you will note from next slide, Sandoz guidance also rates for the top line. For 2023, we now expect Sandoz top line to grow mid-single digit. We are maintaining Sandoz core operating income guidance as expected to decline low double digit for now. This is mainly related to the investments to transition to a separate Sandoz and expected continued inflationary pressures.

正如您將從下一張幻燈片中註意到的那樣，Sandoz 指南也對頂線進行了評級。對於 2023 年，我們現在預計 Sandoz 的收入將增長到中個位數。我們維持 Sandoz 的核心營業收入指引，預計目前將下降兩位數。這主要與過渡到單獨的 Sandoz 的投資和預期的持續通脹壓力有關。

As you can imagine, bottom line performance for business during the separation is a bit more difficult to predict. Therefore, we want to see quarter 2 before considering a guidance upgrade also on the bottom line. Midterm, we expect Sandoz sales to grow low to mid-single-digit CAGR and core operating income margin is expected to expand to the mid-20s driven by continued sales growth and operational efficiencies.

可以想像，分離期間業務的底線績效更難以預測。因此，我們希望在考慮對底線的指導升級之前看到第二季度。中期，我們預計 Sandoz 的銷售額將以低至中個位數的複合年增長率增長，並且在持續的銷售增長和運營效率的推動下，核心營業收入利潤率預計將擴大至 20 年代中期。

On the next slide, I would like to detail some of the important news flow and milestones for the Sandoz business. As mentioned, Sandoz had a good start with 8% sales up, sales in Europe were particularly strong, up 16% and biopharma growth was also very strong at 17%. Sandoz continuing to progress by a similar pipeline, biosimilar adalimumab was approved in both U.S. and Europe, denosumab biosimilar filings -- filing was accepted in the U.S. and we expect the Phase III readout of aflibercept biosimilar in the second half of '23.

在下一張幻燈片中，我想詳細介紹 Sandoz 業務的一些重要新聞流和里程碑。如前所述，Sandoz 開局良好，銷售額增長 8%，歐洲的銷售額尤為強勁，增長 16%，生物製藥增長也非常強勁，達到 17%。 Sandoz 繼續通過類似的管道取得進展，生物仿製藥阿達木單抗在美國和歐洲均獲得批准，denosumab 生物仿製藥申請——申請在美國被接受，我們預計 aflibercept 生物仿製藥的 III 期讀出將在 23 年下半年進行。

The planned spinoff is well on track for the second half of this year. The Capital Market Days are planned in early June in both New York and London. We also announced that Gilbert Ghostine has been appointed as Sandoz Chairman Designate.

計劃中的分拆在今年下半年進展順利。資本市場日計劃於 6 月初在紐約和倫敦舉行。我們還宣布 Gilbert Ghostine 已被任命為 Sandoz 候任董事長。

Just for your information, Novartis implemented a couple of small transfers of certain manufacturing services and our malaria drug Coartem between Sandoz IM it's around $200 million of sales. So it's a very minor impact on segment reporting and the financials related to those. To help your modeling for the future, we will publish these small changes on our website tomorrow, should there be any questions, our Investor Relations team is always ready to help.

僅供參考，諾華公司在 Sandoz IM 之間實施了某些製造服務和我們的瘧疾藥物 Coartem 的一些小額轉移，銷售額約為 2 億美元。因此，這對分部報告和與之相關的財務影響非常小。為了幫助您為未來建模，我們明天將在我們的網站上發布這些小改動，如果有任何問題，我們的投資者關係團隊隨時準備提供幫助。

On the next slide, I'd like to outline again, as I did 3 months ago, the key drivers of core operating income growth for the rest of the year. Expected core operating income growth drivers include the continued strong sales performance of our in-market growth brands and acceleration of recent launches. Pluvicto growth, mainly as of quarter 3 is now also well supported after the just announced FDA approval for our Millburn manufacturing site for the U.S. We expect China growth to accelerate, particularly in the second half of the year. We saw a good quarter 1 of 5%, but not to the usual growth rates we would expect and our team is ready to execute in the reopened market in China.

在下一張幻燈片上，我想再次概述今年剩餘時間核心營業收入增長的主要驅動因素，就像我 3 個月前所做的那樣。預期的核心營業收入增長動力包括我們市場增長品牌的持續強勁銷售業績和近期推出的加速。在剛剛宣布 FDA 批准我們在美國的 Millburn 製造基地後，Pluvicto 的增長（主要是第三季度）現在也得到了很好的支持。我們預計中國的增長將加速，尤其是在今年下半年。我們在第一季度看到了 5% 的良好增長，但沒有達到我們預期的通常增長率，我們的團隊已準備好在中國重新開放的市場中執行。

Our simplified organizational structure and productivity programs are expected to continue delivering SG&A savings and the core operating income growth, if you go to the right side, of course, there are a few headwinds, which we like inflation would expect to continue throughout the year. Of course, we monitor that. If there's any change, we would update you as always.

我們簡化的組織結構和生產力計劃預計將繼續提供 SG&A 節省和核心營業收入增長，如果你走到正確的一邊，當然會有一些不利因素，我們希望通貨膨脹預計將在全年持續。當然，我們對此進行監控。如果有任何變化，我們會一如既往地為您更新。

And also some headwinds from generic erosion as we still continue to have Gilenya generics erosion U.S., Lucentis in Europe. And of course, then the further acceleration of standup investments to transition Sandoz to a standalone company. We had relatively little of the standup investments in quarter 1, but it's also one of the reasons for the expected Core Op Inc decline at Sandoz.

還有一些來自仿製藥侵蝕的不利因素，因為我們仍然繼續讓 Gilenya 仿製藥侵蝕美國，歐洲的 Lucentis。當然，還有進一步加速獨立投資，將 Sandoz 轉變為一家獨立公司。我們在第一季度的獨立投資相對較少，但這也是 Sandoz 預期 Core Op Inc 下滑的原因之一。

In short, I'm convinced we are very well set up to continue our business momentum and are confident in our short-, mid- and long-term growth objectives on both top and bottom line. Last but not least, on the next slide, a few words on the currency impact, noting the constantly changing currencies. In Q1, currency had a negative 5% point impact on net sales and a negative 7-point impact on core operating income.

簡而言之，我相信我們已經做好了繼續保持業務發展勢頭的準備，並對我們的短期、中期和長期增長目標充滿信心。最後但並非最不重要的是，在下一張幻燈片上，就貨幣影響談幾句，注意不斷變化的貨幣。第一季度，貨幣對淨銷售額產生了 5 個百分點的負面影響，對核心營業收入產生了 7 個百分點的負面影響。

Looking forward, if late April rates prevail for the remainder of '23, we expect the full year impact of currencies on the top line to be neutral. And in the bottom line to be negative 3% to negative 4% points, that has mainly to do with the Swiss franc actually strengthening also versus the euro as overall, the dollar has weakened a bit again, but still better than what we had before, and we see a bit of positives on the currencies.

展望未來，如果 4 月底的利率在 23 年的剩餘時間內占主導地位，我們預計貨幣對收入的全年影響將是中性的。底線是負 3% 到負 4%，這主要與瑞士法郎實際上對歐元整體走強有關，美元再次走軟，但仍好於我們之前的水平，我們看到了貨幣的一些積極因素。

As a reminder, in order to help you model these impacts, which is never easy from the outside in, we update the currency impacts expected on our website monthly.

提醒一下，為了幫助您模擬這些從外到內絕非易事的影響，我們每月都會在我們的網站上更新預期的貨幣影響。

And with that, I hand back to Vas.

就這樣，我交還給 Vas。

Thank you, Harry. So moving to Slide 30. Just in conclusion, we had a strong start to 2023, as you heard throughout the call, particularly with Entresto, Kisqali and Kesimpta with broad-based. Our launches are performing well, Pluvicto and Scemblix continue on a strong trajectory and Leqvio is progressing steadily. We're confident in our midterm growth outlook. NATALEE had its positive Phase III readout looking forward to presenting that data. We had positive top line of iptacopan data and consistently not presenting additional data as we move to C3G and IgAN. Pluvicto reading out in earlier lines of therapy, we'll have readouts upcoming with Scemblix, remibrutinib, SMA, (inaudible), amongst others. And with all of that momentum, we're raising our full year guidance, and we'll look forward to continuing the strong operational performance over the course of this year.

謝謝你，哈利。所以轉向幻燈片 30。總而言之，正如您在整個電話會議中所聽到的那樣，我們在 2023 年開局良好，尤其是 Entresto 、 Kisqali 和 Kesimpta 具有廣泛的基礎。我們的發布表現良好，Pluvicto 和 Scemblix 繼續保持強勁勢頭，而 Leqvio 正在穩步發展。我們對中期增長前景充滿信心。 NATALEE 有其積極的 III 期讀數，期待展示該數據。我們有正面的 iptacopan 數據，並且在我們轉向 C3G 和 IgAN 時始終沒有提供額外的數據。 Pluvicto 在早期治療系列中的讀數，我們將在 Scemblix、remibrutinib、SMA（聽不清）等方面進行讀數。憑藉所有這些勢頭，我們正在提高全年指導，我們期待在今年繼續保持強勁的運營業績。

So with that, I'll open the line to questions. I would ask each of the questioners to limit themselves to one question. In addition, because our presentation was a bit shorter today, we'll aim to end the questioning period at 3:15 Central European Time. So operator, you can open the line for questions.

因此，我將開始提問。我會要求每個提問者將自己限制在一個問題上。此外，由於我們今天的演講時間稍短，我們的目標是在歐洲中部時間 3:15 結束提問期。接線員，您可以打開問題熱線。

(Operator Instructions) And your first question comes from the line of Graham Parry, Bank of America.

（操作員說明）您的第一個問題來自美國銀行的 Graham Parry。

So predictably on Kisqali naturally, you've spoken in the past to about the adjuvant and early breast cancer opportunity being around a $6 billion addressable market. And I know you don't want to share too much more of the data, but do you think that your data is consistent with that sort of market opportunity?

所以在 Kisqali 上自然可以預見，你過去曾談到輔助和早期乳腺癌的機會是一個大約 60 億美元的潛在市場。我知道你不想分享太多的數據，但你認為你的數據與那種市場機會一致嗎？

Yes. Thanks, Graham. I think the opportunity would continue to be in that range based on the data or the key driver will be how much uptake we can drive in the Stage 2 patient population, so those with node-negative patients given that there is more reluctance, I think, amongst physicians to start patients on additional lines of therapy. But -- we believe that the data is strong enough overall that there should be broad use across both Phase II/III patients at risk with breast cancer, including node-negative patients. Next question, operator.

是的。謝謝，格雷厄姆。我認為，根據數據，機會將繼續處於該範圍內，或者關鍵驅動因素將是我們可以在第 2 階段患者人群中推動多少吸收，因此我認為那些淋巴結陰性患者更不願意, 在醫生中開始患者接受額外的治療。但是——我們認為數據總體上足夠強大，應該廣泛用於有乳腺癌風險的 II/III 期患者，包括淋巴結陰性患者。下一個問題，接線員。

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

你的下一個問題來自瑞士信貸的 Matthew Weston。

My question is about the R&D pipeline. It's quite notable that in the quarter, I think 20 Phase I and Phase II trials were removed from your pipeline roster and you only added 2, in particular, it looks like a deep prune in oncology. I'd be very interested if it's a change in strategy, whether it's a clean out and we should expect a refresh of new projects in the coming quarters or whether it's a key focus of reducing cost in early stage to concentrate on some of those new Phase III trials that you set out in your opening comments, Vas.

我的問題是關於研發渠道的。值得注意的是，在本季度，我認為 20 項 I 期和 II 期試驗已從您的管道名冊中刪除，您只添加了 2 項，特別是，它看起來像是腫瘤學的深度修剪。如果它是戰略上的變化，我會非常感興趣，無論是清理還是我們應該期待在未來幾個季度更新新項目，或者它是否是早期降低成本以專注於其中一些新項目的關鍵重點Vas，您在開場白中提出的 III 期試驗。

Yes. Thanks, Matthew. So I think there are a couple of dynamics here. First, as we've outlined, starting with our Capital Markets Day last year, we have a clear strategy in 5 therapeutic areas plus TAX where we house our renal and ophthalmology gene therapy programs. And what we did is we systematically looked at the pipeline to identify projects that were outside the scope of those core therapeutic areas or in the case of oncology, we're addressing tumors that are no longer priority tumors for the company and we wanted to stop those projects.

是的。謝謝，馬修。所以我認為這裡有一些動態。首先，正如我們所概述的那樣，從去年的資本市場日開始，我們在 5 個治療領域以及我們負責腎臟和眼科基因治療項目的 TAX 制定了明確的戰略。我們所做的是，我們系統地研究了管道，以確定那些核心治療領域範圍之外的項目，或者在腫瘤學的情況下，我們正在解決不再是公司優先腫瘤的腫瘤，我們想停止那些項目。

And so I think that was probably the biggest driver of the shift you see. However, also when we benchmarked ourselves versus the peer set, we thought that we had more projects than our peers, which led to us had less investment per project versus the peer set. And we think that's important because I think having strong investment in the early stage preclinically or an early clinical can also help us go faster, go broader into more lines of therapy, more indications. So we want to get up on that -- those metrics also with the goal of having more high-value medicines generated from the pipeline. So I think that was the second shift that was on our minds as we made this clean -- "cleanup" of the portfolio.

所以我認為這可能是你所看到的轉變的最大驅動力。然而，當我們將自己與同行進行基準比較時，我們認為我們的項目比同行多，這導致我們每個項目的投資比同行少。我們認為這很重要，因為我認為在早期臨床前階段或早期臨床階段進行大量投資也可以幫助我們走得更快，更廣泛地進入更多的治療領域，更多的適應症。因此，我們希望在這一點上取得進展——這些指標的目標也是從管道中產生更多高價值的藥物。所以我認為這是我們在清理投資組合時想到的第二個轉變。

Now I think looking forward to your specific question in oncology, we have identified 5 tumor types we're particularly interested in, and we're trying to focus our energy there. We also want to pivot much harder to RLT-based therapies where we see the strong performance of Pluvicto and Lutathera, so I think that was also on our mind. So I would hope that you will see -- I don't know about a higher number of projects but higher quality projects in our oncology portfolio going forward. Thanks for the question, Matthew. Next question, operator?

現在我想期待你在腫瘤學方面的具體問題，我們已經確定了 5 種我們特別感興趣的腫瘤類型，我們正在努力將我們的精力集中在那裡。我們還希望更加努力地轉向基於 RLT 的療法，我們看到 Pluvicto 和 Lutathera 的強勁表現，所以我認為這也在我們的腦海中。所以我希望你會看到——我不知道我們的腫瘤組合中的項目數量會更多，但質量會更高。謝謝你的問題，馬修。下一個問題，運營商？

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

你的下一個問題來自法國巴黎銀行的理查德帕克斯。

Congratulations on a great quarter. The question is on remibrutinib, you brought forward the readout in CSU to next year. Obviously, there's been more news on the liver toxicity profile of the class recently. So I just wondered if you could update us on what you've seen so far in the clinical program, what monitoring you have in place? And any reason to believe that remibrutinib could have a differentiated profile there?

祝賀一個偉大的季度。問題是關於 remibrutinib，你將 CSU 的讀數提前到明年。顯然，最近有更多關於該類藥物肝毒性的新聞。所以我只是想知道你是否可以向我們更新你到目前為止在臨床計劃中看到的情況，你有什麼監控？有什麼理由相信 remibrutinib 可以在那裡具有差異化特徵？

Yes. Thanks, Richard. So just to clarify, the CSU readout that we would expect over the course of the summer is a 12-week efficacy readout. The relevant regulatory authorities have asked us for additional safety follow-up. So the study, we would top line the study if positive or negative. And then if positive, the study would continue and we would monitor for safety prior to a regulatory filing in 2024 in CSU.

是的。謝謝，理查德。因此，澄清一下，我們預計整個夏季的 CSU 讀數是 12 週的療效讀數。相關監管機構已要求我們進行額外的安全跟進。所以這項研究，無論是積極的還是消極的，我們都會將這項研究放在首位。然後，如果結果是肯定的，該研究將繼續進行，我們將在 2024 年向 CSU 提交監管文件之前監控安全性。

Overall, now we have 1,600 patients exposed to the medicine across a range of doses. And we have yet to see any signs of liver toxicities, LFT, problematic LFT elevations. Our best hypothesis at the moment is that given that the BTK receptor is not expressed in the liver, that this is -- that the toxicities our competitors are seeing are primarily compound-related, and our hope is that our chemistry has avoided that. But there's no guarantees. We foresee to fully run these studies both in CSU and in multiple sclerosis where we have 2 studies ongoing in RMS. If the current profile holds, we have the opportunity to, hopefully, to have a unique profile versus our compare set. It's our position that this should not be considered a cost effect given that it seems to be compound specific and not mechanistically driven, but that's obviously something we'll also have to take up with the regulators as the data continues to unfold. Next question, opeator?

總體而言，現在我們有 1,600 名患者接觸了各種劑量的藥物。我們還沒有看到任何肝毒性、LFT、有問題的 LFT 升高的跡象。我們目前最好的假設是，鑑於 BTK 受體不在肝臟中表達，這是——我們的競爭對手看到的毒性主要與化合物相關，我們希望我們的化學避免了這種情況。但沒有任何保證。我們預計將在 CSU 和多發性硬化症中全面開展這些研究，我們在 RMS 中正在進行 2 項研究。如果當前配置文件成立，我們有希望擁有一個獨特的配置文件與我們的比較集。我們的立場是，這不應被視為成本效應，因為它似乎是化合物特定的而不是機械驅動的，但這顯然是我們還必須隨著數據的繼續展開而與監管機構討論的問題。下一個問題，接線員？

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。

Question on Leqvio, if I may. As you showed on Slide 17, you are tracking nicely, if not slightly above the Entresto launch, but I'm guessing at some point, we should still expect it to be an inflection. And I just wanted to get an update on, on how close we are. When one looks at the numbers of facilities that have ordered, the HCPs with like experience, presumably at some point, that linear trend starts to move up. And I just wonder if you could give us any update on how far you think you are from a point when the trend starts to exceed interesting?

如果可以的話，關於 Leqvio 的問題。正如你在幻燈片 17 上展示的那樣，你的跟踪很好，即使不是略高於 Entresto 發布，但我猜在某個時候，我們仍然應該期望它是一個拐點。我只是想了解我們的進展情況。當人們查看已訂購的設施數量時，具有類似經驗的 HCP 可能在某個時候，這種線性趨勢開始上升。我只是想知道您是否可以向我們提供任何最新信息，說明您認為您離趨勢開始變得有趣的時間點還有多遠？

Yes. Thanks, Simon. So as I said, I think the adoption now is very broad-based, and that's a positive, positive trend. The biggest topic for us is to getting more depth per physician office that orders. And that's something we're very focused on. It primarily has to do with comfort with the buy-and-bill process, understanding the reimbursement process. Also, to add additional patients in buying bills, in some instances, that means may mean more administrative capacity in the relevant ordering facility.

是的。謝謝，西蒙。所以正如我所說，我認為現在的採用非常廣泛，這是一個積極的趨勢。對我們來說最大的話題是讓每個醫生辦公室獲得更多的深度。這是我們非常關注的事情。它主要與購買和賬單流程的舒適度有關，了解報銷流程。此外，在某些情況下，在購買賬單時增加更多患者，這可能意味著相關訂購設施的管理能力更強。

So it's difficult to predict exactly, but we continue to hope that over the course of the next 6 months, we'll start to see increasing depth, which then should compound over the course of next year to lead us to maintain or, I mean, ideally beat the Entresto curve. But I think at this point, our aspiration is to stay on that Entresto curve, which has driven, I think, pretty impressive overall sales for Entresto over time. And so that's where we're tracking at the moment. As we see anything shift in the marketplace, we'll, of course, let you know. Next question, operator?

所以很難準確預測，但我們仍然希望在接下來的 6 個月裡，我們會開始看到深度增加，然後在明年的過程中應該會復合，讓我們保持，或者，我的意思是，理想情況下擊敗 Entresto 曲線。但我認為在這一點上，我們的願望是保持在 Entresto 曲線上，我認為隨著時間的推移，它推動了 Entresto 的整體銷售。這就是我們目前正在追踪的地方。當我們看到市場發生任何變化時，我們當然會通知您。下一個問題，運營商？

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

你的下一個問題來自摩根士丹利的 Mark Purcell。

Vas, I hope you could give us some insights into how you feel the prostate cancer space is going to be treated going forward. As you move from the post-taxane to the pre-taxane setting. Obviously, there's Pluvicto and there's other radio therapies, which are going to hopefully help the uptick of that category, thinking of, for example, Point Biopharma's PMC2002 where we're going to get pipette in the same setting -- in the Q4 period, but there's also ADCs entering this space as well. So I just wanted to help us understand logistical and other challenges of radioligand therapy versus ADCs, for example, and where you think this is going to go in the pre-taxane setting?

Vas，我希望你能給我們一些見解，讓我們了解你對前列腺癌領域未來治療的看法。當您從紫杉烷後設置轉移到紫杉烷前設置時。顯然，有 Pluvicto 和其他放射療法，它們有望幫助該類別的增長，例如，考慮 Point Biopharma 的 PMC2002，我們將在相同的設置下使用移液器——在第四季度，但也有 ADC 進入這個領域。因此，我只是想幫助我們了解放射配體療法與 ADC 相比的後勤和其他挑戰，例如，您認為這將在紫杉烷前環境中走向何方？

Yes. Thanks, Mark. When you look at Pluvicto and why you've seen such a strong uptake, I think it's a couple of things. One is surely the strong overall benefit risk profile. You have a solid efficacy profile, a very good safety profile, probably better in practice than we had expected, and the opportunity to cycle patients to 6 doses or 4 to 6 doses, depending on the situation and not have them be on chronic therapy. That's led to a significant increase, at least as we've seen in capacity for radioligand therapies at centers across the United States, given that also there already is very good capacity for F-18 diagnostics for looking at these patients.

是的。謝謝，馬克。當你看 Pluvicto 以及為什麼你看到如此強烈的吸收時，我認為這是兩件事。其中之一肯定是強大的整體收益風險狀況。你有可靠的療效，非常好的安全性，在實踐中可能比我們預期的要好，並且有機會根據情況將患者循環至 6 劑或 4 至 6 劑，而不是讓他們接受長期治療。這導致顯著增加，至少正如我們在美國各地的中心看到的放射配體治療能力一樣，考慮到 F-18 已經有很好的診斷能力來觀察這些患者。

So I think right now, the capacity increase is quite substantial, at least what we're seeing to enable us to move into the pre-taxane setting and not have logistics be a topic. We also believe our expertise that we've now developed over the last year in terms of supply chain, having now 3 full-scale manufacturing sites, we hope by the end of the year, servicing the U.S. population, but also the global population with plans to add additional capacity would make us the clear leader in terms of being able to reliably supply these medicines to patients across the globe and across the United States.

所以我認為現在，產能的增加是相當可觀的，至少我們所看到的使我們能夠進入紫杉醇前的環境，而不是讓物流成為一個話題。我們也相信我們在過去一年中在供應鏈方面發展起來的專業知識，現在擁有 3 個全面的製造基地，我們希望到今年年底，為美國人口以及全球人口提供服務增加額外產能的計劃將使我們成為能夠向全球和美國各地的患者可靠地供應這些藥物的明確領導者。

So I feel pretty comfortable that, of course, there's always going to be different options. You have the ARDT. As you mentioned, you have ADCs, you have many different options. But I think -- given the profile of Pluvicto and if the data continues to demonstrate its benefit, there will be a solid significant proportion of patients in the metastatic setting in the pre-taxane setting that will choose to use Pluvicto with their providers. And I don't think logistics constraints will be the issue.

所以我覺得很舒服，當然，總會有不同的選擇。你有 ARDT。正如你提到的，你有 ADC，你有很多不同的選擇。但我認為——考慮到 Pluvicto 的概況，如果數據繼續證明它的好處，在紫杉烷前環境中的轉移環境中，將有相當大比例的患者選擇與他們的提供者一起使用 Pluvicto。而且我認為後勤限制不會成為問題。

Now as we move into earlier lines of therapy and we look at delayed castration or other settings, that's another ball game. And there, I think we would have to find ways to expand the ability to administer radioligand therapies further into the community. There, I do think we would need to do some additional -- quite a bit of additional work to expand that capacity. But we, of course, have time for that. Those readouts are still 3 years plus out. And by that time, I hope we would have better solutions for community oncologists to be able to administer radioligand therapies. So bottom line is I think these can all coexist and I think it still supports multibillion-dollar potential for each of the Pluvicto indications, if ultimately successful. Next question, operator?

現在，當我們進入更早的治療線，並研究延遲閹割或其他設置時，那是另一場球賽。在那裡，我認為我們必須找到方法將放射配體療法的管理能力進一步擴展到社區。在那裡，我確實認為我們需要做一些額外的——相當多的額外工作來擴大這種能力。但是，我們當然有時間。那些讀數仍然超過 3 年。到那時，我希望我們能為社區腫瘤學家提供更好的解決方案，使他們能夠進行放射配體治療。所以底線是我認為這些都可以共存，我認為如果最終成功，它仍然支持每個 Pluvicto 適應症的數十億美元潛力。下一個問題，運營商？

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

你的下一個問題來自摩根大通的 Richard Vosser。

I just wanted to follow up on Pluvicto as well. And just thinking about your supply into the second half as you ramp up the Millburn facility. So just some thoughts on the proportion of the '24 target you might be for doses you might be able to have available in Q3 and by the end of the year, just to give us some idea of how that supply is going to phase as we go forward in the second half?

我也想跟進 Pluvicto。當你擴大米爾本工廠時，想想你下半年的供應。因此，關於您可能在第三季度和年底之前可以獲得的劑量在 24 年目標中所佔比例的一些想法，只是為了讓我們了解供應將如何分階段進行下半場繼續前進？

Yes. Thanks, Richard. I'd say, broadly, we believe we're comfortable that Pluvicto will exceed $1 billion in sales over the course of this year. And by how much will largely be dependent on when the additional lines are operational in Millburn, which we're working very hard on to file those lines with FDA. And because this is an approved facility, that review is a relatively short review. And then ultimately, the Indianapolis facility, which we're also raising now to file as well, which would lead to a further unlock. So difficult at this moment to dimensionalize the scale above that $1 billion mark. And I think as we get those lines operational, I think by Q2, we can provide some better color on the scale of the supply increase. Next question, operator?

是的。謝謝，理查德。我想說，從廣義上講，我們相信我們對 Pluvicto 今年的銷售額將超過 10 億美元感到滿意。多少將在很大程度上取決於額外生產線何時在 Millburn 投入運營，我們正在努力向 FDA 提交這些生產線。因為這是一個批准的設施，所以該審查是一個相對較短的審查。然後最終，印第安納波利斯設施，我們現在也提出申請，這將導致進一步解鎖。目前很難確定超過 10 億美元大關的規模。而且我認為，當我們讓這些生產線投入運營時，我認為到第二季度，我們可以在供應增加的規模上提供一些更好的顏色。下一個問題，運營商？

Your next question comes from the line of Emmanuel Papadakis from DB.

您的下一個問題來自 DB 的 Emmanuel Papadakis。

Perhaps I would take one on the longer-term implications of (inaudible) financial outlook. So on the one hand, your previous margin guidance, getting above 40% from 2027. Does this reaffirm that outlook? Or does it actually potentially tip the probabilities to the upside of that. And then on the other hand, your best estimate at the timing of potential IRA inclusion, price negotiation if the commercial opportunity proceeds as we hope it may.

也許我會考慮（聽不清）財務前景的長期影響。因此，一方面，你之前的利潤率指導，從 2027 年開始超過 40%。這是否重申了這一前景？或者它實際上是否有可能將概率推高。另一方面，如果商業機會如我們希望的那樣進行，您對可能包含 IRA 的時間、價格談判的最佳估計。

Yes. Thanks, Emmanuel. So first on the margin, I'll give it to Harry. Harry?

是的。謝謝，伊曼紐爾。因此，首先，我將把它交給哈利。哈利？

Yes. Emmanuel, thank you for your question. I mean, overall, of course, as we do our 5- to 10- to 15-year forecast on which we base our guidance to you all. There's, of course, a portfolio with certain probabilities and all of that. We had, I would say, the NATALEE trial as an appropriate Phase III high probability. I would say, as we always mentioned, that was one of the disconnects of the consensus to our 4% CAGR.

是的。伊曼紐爾，謝謝你的提問。我的意思是，總體而言，當然，當我們進行 5 到 10 到 15 年的預測時，我們將根據這些預測為大家提供指導。當然，有一個具有一定概率的投資組合等等。我想說，我們有 NATALEE 試驗作為適當的 III 期高概率試驗。我會說，正如我們一直提到的那樣，這是與我們 4% 的複合年增長率達成共識的脫節之一。

As I think when I looked at the consensus, there was almost nothing in the consensus for NATALEE, which I always find a bit strange, but in the end, everybody makes the estimates. So that is certainly -- we increased our own, of course, modeling now from a Phase III, call it, 70%, 80% probability, to 100%, right, if you will, of course, approval still have to happen. But we are close to that. So it's positive. It's certainly supporting our case. And I think that the confidence levels go up.

我看共識的時候覺得，NATALEE的共識幾乎什麼都沒有，我總覺得有點奇怪，但最後大家還是做了預估。所以這當然是——我們當然增加了我們自己的模型，現在從第三階段開始，稱之為 70%，80% 的概率，到 100%，對，如果你願意，當然，批准仍然必鬚髮生。但我們已經接近了。所以這是積極的。它肯定支持我們的情況。我認為信心水平會上升。

Now on the other hand, the 40%, I mean we always had very strong plans for 40% to hit that margin in '27. Again, when the top line is great on high-margin products, that is always helpful, often I get the question and what beyond the 40%. I think let's first get to the 40%. And recall that 40% is for the new Novartis after the Sandoz spin. So it also includes roughly 1.3 points of corporate costs, right, which was back then when we gave guidance basically in inherent upgrade. And then beyond that really depends on the product mix. But let's first get to the 40%. Once we get closer, we will have more visibility on the mix beyond. But I think it's anyway important that we and you are confident in our top line growth, right, which is always the most important and the pipeline.

現在另一方面，40%，我的意思是我們一直有非常強大的計劃，讓 40% 的人在 27 年達到這個利潤率。同樣，當高利潤產品的收入很高時，這總是有幫助的，我經常會問這個問題，以及超出 40% 的是什麼。我想讓我們先達到 40%。回想一下，在 Sandoz 旋轉之後，40% 用於新諾華。所以它還包括大約 1.3 個點的企業成本，對，這是當時我們基本上在固有升級方面給出指導的時候。然後除此之外真的取決於產品組合。但讓我們先來看看 40%。一旦我們走近了，我們將對遠處的混合有更多的了解。但我認為無論如何重要的是我們和你對我們的收入增長充滿信心，對，這始終是最重要的和管道。

And then I think, Emmanuel, on IRA, the Kisqali today roughly about 1/3 of the patients are Medicare patients. So I think it's early days for us to forecast when exactly it would fall within the IRA. I think that we've previously stated we would expect it to be at the end of the decade, given that Kisqali's LOE would be in the early 2030s. We think it would roughly coincide. But obviously, with the NATALEE data, now we'd have to obviously observe that over the coming years to get a better estimate of when we might qualify in our Medicare sales and also depending on how CMS ultimately measures the sales. As you know, that's an ongoing topic. And one -- certainly, the industry is planning to provide a full opposition to maybe some of the unfair approaches that are currently being taken by CMS at least in our view. Next question, operator?

然後我認為，Emmanuel，在 IRA 上，Kisqali 今天大約有 1/3 的患者是 Medicare 患者。所以我認為我們現在預測它何時會落入 IRA 還為時過早。我認為我們之前已經說過，我們預計它會在本世紀末出現，因為 Kisqali 的 LOE 將在 2030 年代初出現。我們認為這將大致重合。但很明顯，有了 NATALEE 數據，現在我們必須在未來幾年明顯觀察到這一點，以便更好地估計我們何時可能符合 Medicare 銷售的條件，並取決於 CMS 最終如何衡量銷售。如您所知，這是一個持續的話題。一個 - 當然，至少在我們看來，該行業正計劃全面反對 CMS 目前正在採取的一些不公平的方法。下一個問題，運營商？

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

您的下一個問題來自 Cowen 的 Stephen Scala。

As noted earlier, when describing NATALEE results, Novartis refers to the benefit as consistent. When using the word consistent, we assume Novartis is referring to a consistent hazard ratio across and among all the relevant groups depicted on Slide 8. Is that the expectation you want investors to have heading into the readout? Or should that expectation be modified?

如前所述，在描述 NATALEE 結果時，諾華稱其益處是一致的。當使用一致這個詞時，我們假設諾華公司指的是幻燈片 8 中描述的所有相關組之間的一致風險比。這是您希望投資者進入讀數的期望嗎？還是應該修改這種期望？

Yes. Thanks, Steven. Thanks, Stephen. So we don't want to provide excess data here, given that we have committed to present the data at upcoming medical Congress. We want to preserve that and also preserve our ability to publish the data in a major medical journal. But certainly, when we say consistent benefit in a -- when we say consistent benefit in a broad population of patients with Stage 2 and 3 early breast cancer at risk of recurrence, we're referring to the primary endpoint in the study. And I think that is always what we're referring to when we look at that data. And I think then you can interpret that as you will, it will be hopefully soon that you'll be able to see the full data set and understand better the specifics, both from the primary endpoint, but also the trends in OS as well. Next question, operator.

是的。謝謝，史蒂文。謝謝，斯蒂芬。所以我們不想在這裡提供過多的數據，因為我們已經承諾在即將召開的醫學大會上展示這些數據。我們希望保留這一點，並保留我們在主要醫學期刊上發表數據的能力。但可以肯定的是，當我們說持續受益時——當我們說對有復發風險的 2 期和 3 期早期乳腺癌患者的廣泛人群持續受益時，我們指的是研究中的主要終點。我認為，當我們查看這些數據時，這始終是我們所指的。我認為你可以隨心所欲地解釋它，希望很快你就能看到完整的數據集並更好地理解細節，既有主要終點，也有操作系統的趨勢。下一個問題，接線員。

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

你的下一個問題來自巴克萊銀行的 Emily Field。

I had another question on Kisqali. I believe you discussed earlier today about developing potential partner assets for Kisqali. And I was just wondering if you could give any insights just into how you're thinking about that. Obviously, the oral third class in combination with CDK4/6 has been a focus of some competitors. So would that be an idea? Or just any insights you can provide there would be helpful.

我還有一個關於 Kisqali 的問題。我相信您今天早些時候討論過為 Kisqali 開發潛在的合作夥伴資產。我只是想知道您是否可以就您的想法給出任何見解。顯然，與CDK4/6組合的口試三等已經成為部分參賽者關注的焦點。那會是個主意嗎？或者您可以提供的任何見解都會有所幫助。

Yes. Thanks, Emily. I think my comments earlier today were mostly referring to our internal programs to develop additional mechanisms that we think would be relevant for the breast cancer setting. So that would include, of course, the CDK2 class perhaps a stronger CDK4, CDK2/4. So we have a number of projects ongoing within the research unit with -- in NIBR to look at additional oral agents that can target the various elements of the cyclin-dependent kinase cascades. So that's, I think, a big area of focus.

是的。謝謝，艾米麗。我想我今天早些時候的評論主要是指我們的內部計劃，以開發我們認為與乳腺癌相關的其他機制。所以這當然包括 CDK2 類，也許是更強的 CDK4，CDK2/4。因此，我們在研究部門內正在進行許多項目——在 NIBR 中，研究可以針對細胞週期蛋白依賴性激酶級聯的各種元素的其他口服藥物。所以我認為這是一個很大的重點領域。

We also continue to evaluate in-house if there is a role for any of our radioligand therapies as well as our own in-house ADC programs as well. It is a priority for us to build a deeper breast cancer portfolio behind Kisqali, but it's all very early. And I think it's something we want to address now given the probably a very strong decade we expect to see with Kisqali in the position we'll build in breast cancer to make sure we have a steady portfolio. So I think more to come on how we progress those internal assets as we get more preclinical than hopefully clinical data. Next question, operator?

我們還將繼續在內部評估我們的任何放射配體療法以及我們自己的內部 ADC 程序是否有作用。在 Kisqali 背後建立更深入的乳腺癌產品組合是我們的首要任務，但這一切還為時過早。我認為這是我們現在想要解決的問題，因為我們預計可能會看到 Kisqali 處於我們將在乳腺癌中建立的位置，以確保我們擁有穩定的投資組合。因此，隨著我們獲得更多的臨床前數據而不是希望的臨床數據，我認為更多的是關於我們如何發展這些內部資產。下一個問題，運營商？

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

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

Thank you. On NATALEE, we obviously don't have the data, but in high-risk patients on side-by-side analysis, what can you say for how it compares to Lilly's Verzenio even just a qualitative description efficacy and tolerability? And then you mentioned in intermediate patients and especially no negative it might be more challenging to drive uptake. And I'm wondering why is that focused primarily on tolerability and NATALEE use a lower dose, of course, to mitigate tolerability what can you say about the tolerability in NATALEE at that lower dose in general?

謝謝。關於 NATALEE，我們顯然沒有數據，但在並排分析的高危患者中，你能說說它與禮來的 Verzenio 相比如何，即使只是定性描述療效和耐受性？然後你提到在中間患者中，尤其是沒有消極的情況下，推動吸收可能更具挑戰性。我想知道為什麼這主要集中在耐受性上，而 NATALEE 使用較低的劑量，當然，為了減輕耐受性，你能說說 NATALEE 在一般較低劑量下的耐受性嗎？

Yes. Thanks, Tim. So I won't repeat what I said to Steve. Obviously, we don't want to, in any way, impact our ability to present and publish the data set in the upcoming periods. So not much more I can say the data is consistent. We believe clinically compelling and we said that it's clinically meaningful and I think it's been well described in all of your reports as to what it requires to be clinically meaningful. In fact, I probably can't characterize it any further than what I've already said.

是的。謝謝，蒂姆。所以我不會重複我對史蒂夫說過的話。顯然，我們不想以任何方式影響我們在未來一段時間內展示和發布數據集的能力。所以我只能說數據是一致的。我們相信在臨床上具有說服力，我們說它具有臨床意義，我認為在你們所有的報告中都很好地描述了它需要什麼才能具有臨床意義。事實上，除了我已經說過的，我可能無法進一步描述它的特徵。

Now with respect to node-negative patients that's not related to our tolerability profile. That's more just clinical practice where we need to now educate physicians that there -- it remains risk for recurrence in node-negative patients, and that those patients also would benefit from CDK4/6 on top of endocrine therapy. So it's much more of a, I think, a patient -- physician education and changing clinical practice nothing to do with the safety profile that we've seen.

現在關於與我們的耐受性概況無關的淋巴結陰性患者。這更只是臨床實踐，我們現在需要教育醫生——淋巴結陰性患者仍有復發的風險，而且這些患者在內分泌治療之外也將從 CDK4/6 中獲益。因此，我認為，它更像是一個病人——醫生教育和不斷變化的臨床實踐與我們所看到的安全狀況無關。

As you noted, we took it down to 400 -- we took it slowly down to 400 milligrams based on our belief that this would give us a better safety profile and there has been a Phase II study, the AMELI study, which looked at that clinical profile to show you, at least give you an indication of how the drug performs at the 400-milligram dose level. Next question, operator?

正如您所指出的，我們將其降至 400 毫克——我們將其緩慢降至 400 毫克，因為我們相信這會給我們帶來更好的安全性，並且已經進行了一項 II 期研究，即 AMELI 研究，該研究著眼於向您展示的臨床概況，至少讓您了解藥物在 400 毫克劑量水平下的表現。下一個問題，運營商？

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

你的下一個問題來自 Berenberg 的 Kerry Holford。

A question please on business development. I'd just love to here your latest thoughts here. What is your appetite for external R&D opportunities either in the form of partnerships, acquisitions. And I guess [Otis] has been reasonably quiet on BD over the past year or so. And clearly, many of your peers picking up the pace here now. Has Novartis tried and failed to secure some deals in this recent planning pre? Yes, I'd just love to hear your latest thoughts with regard to appetite or the size of deal tertiary focus.

請問一個關於業務發展的問題。我只是想把你最新的想法放在這裡。您對合作、收購等形式的外部研發機會有何興趣？我想 [Otis] 在過去一年左右的時間裡對 BD 一直相當安靜。很明顯，你們的許多同行現在都在加快步伐。 Novartis 是否在最近的計劃中嘗試並未能獲得一些交易？是的，我很想听聽您對胃口或交易規模的最新看法。

Yes. Thanks, Kerry. There's no change in our strategic thinking on how we approach BD and M&A. I would agree we've been relatively quiet over the last year, but we've also had a major transformation program ongoing and also focused on accelerating our internal assets. And I think that's borne fruit with the positive readouts of Pluvicto, iptacopan, Kisqali as well as the additional assets I outlined on the call. But we are very actively looking across a range of both partnering, licensing and of course, bolt-on M&A. And we continue to focus primarily in the sub-$5 billion range, as we've outlined. We, of course, look at all deals and deal sizes given our strength of our balance sheet, but we want to stay extremely financially disciplined. I mean I think one thing that's a priority for us as a management team, if you look at the signs, is it compelling strategically, but importantly, is there a clear and compelling case for value creation given the premiums that are paid.

是的。謝謝，克里。我們對如何處理 BD 和 M&A 的戰略思考沒有改變。我同意我們在過去一年相對平靜，但我們也正在進行一項重大轉型計劃，並且還專注於加速我們的內部資產。我認為 Pluvicto 、 iptacopan 、 Kisqali 的積極讀數以及我在電話會議上概述的其他資產已經結出果實。但我們正在非常積極地尋找一系列合作、許可，當然還有補強併購。正如我們概述的那樣，我們繼續主要關注低於 50 億美元的範圍。鑑於我們的資產負債表實力，我們當然會考慮所有交易和交易規模，但我們希望在財務上保持高度紀律。我的意思是，我認為作為一個管理團隊，我們優先考慮的一件事是，如果你看一下這些跡象，它在戰略上是否具有吸引力，但重要的是，考慮到所支付的溢價，是否有一個明確且令人信服的價值創造案例。

And we don't want to get into the situation where we pay out so much value that in the end, we're not able to generate value for the company or our shareholders. So that's, I think, a high priority on our mind as we look at the external environment.

我們不想陷入這樣的境地：我們付出了太多的價值，以至於最終無法為公司或我們的股東創造價值。因此，我認為，當我們審視外部環境時，這是我們頭腦中的一個高度優先事項。

So we hope to, of course, execute some additional deals in our core therapeutic areas over the coming year. But I think given our positive readouts, we also don't feel pressured to do that. We'll do it if it makes sense scientifically and strategically. Next question, operator?

因此，我們當然希望在來年在我們的核心治療領域執行一些額外的交易。但我認為，鑑於我們的積極讀數，我們也不會感到有這樣做的壓力。如果它在科學和戰略上有意義，我們就會這樣做。下一個問題，運營商？

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

你的下一個問題來自 Jefferies 的 Peter Welford。

Just a sort of broad question in terms of -- we've obviously been very strong commercial performance during the first quarter that I think surpass certainly most people's expectations, but at the same time, we're obviously undergoing a pretty big strategic review and also obviously a lot of changes in the commercial organization. So just curious, is it that there hasn't really been an impact to or any disruption from this? And I wonder if you could sort of update us how far you are through now sort of acting in terms of the headcount reductions and some of the changes that have done with that review. And therefore, should we, in fact, anticipate that actually some of the commercial focus and performance could improve during the rest of the year? Or are we just, I guess, just wrong in assuming that there was any disruption in the first place, and this has all been managed. And in fact, you've seen with the greater focus actually already the benefits of the change in the structure that we see with the company.

只是一個廣泛的問題——我們在第一季度的商業表現顯然非常強勁，我認為這肯定超出了大多數人的預期，但與此同時，我們顯然正在進行相當大的戰略審查，並且商業組織也明顯發生了很多變化。所以很好奇，是否真的沒有影響或任何干擾？我想知道你是否可以告訴我們你現在在裁員和通過審查所做的一些改變方面採取了多遠的行動。因此，事實上，我們是否應該預計在今年剩餘時間裡，一些商業重點和業績可能會有所改善？或者我們只是，我猜，只是錯誤地假設首先有任何中斷，而這一切都得到了管理。事實上，你已經更加關注我們在公司中看到的結構變化帶來的好處。

Thanks, Peter, and I appreciate the question. So to be clear, we believe the performance we're seeing in Q1 is a result of the focused strategy we implemented over the course of last year which is largely executed other than a few countries in Europe. It's largely in place. And there were a few key drivers. One, the simplification of the organizational structure as well as the focus on the United States as a key market. Second, identifying the 9 key brands and putting all -- most of our M&S focus on those 9 key brands to drive outstanding growth, which also created a higher degree of organizational focus on those brands. I think also ensuring that all of the incentives and all of the various elements are focused on driving the performance of those brands as a pure-play innovative medicine company. I believe all of that has led to, I think, a very strong performance in Q1, which we expect to continue. But Harry, anything you'd want to add?

謝謝，彼得，我很欣賞這個問題。所以要明確一點，我們認為我們在第一季度看到的表現是我們在去年實施的重點戰略的結果，該戰略主要在歐洲的幾個國家以外執行。它基本上就位。還有一些關鍵驅動因素。一是精簡組織架構，聚焦美國作為重點市場。其次，確定 9 個關鍵品牌並將所有 - 我們的大部分 M&S 都集中在這 9 個關鍵品牌上以推動顯著增長，這也使組織更加關注這些品牌。我認為還要確保所有激勵措施和所有各種要素都集中在推動這些品牌作為一家純粹的創新醫藥公司的業績。我相信所有這些都導致了第一季度的強勁表現，我們預計這種情況會繼續下去。但是哈利，你有什麼想補充的嗎？

I think you said it all. And I think what people always were a bit concerned when we did the transformation for growth program, which probably many people understood there's only a restructuring it's actually not the case was about focus. Yes, there was also given the internal merger mainly between pharma and Onco, restructuring elements. But in the end, that led to more focus. And of course, still, we are working on some things fine tuning, but I think that focus on the commercial side as well as on the key assets has led to a lot of clarity, and therefore, good uptake that we see. And as Vas mentioned, we do not expect that to slow down much.

我想你都說了。而且我認為當我們進行增長計劃轉型時，人們總是有點擔心，這可能很多人都知道這只是重組，但實際上並非如此，重點是重點。是的，還有主要是製藥公司和 Onco 之間的內部合併，重組因素。但最終，這導致了更多的關注。當然，我們仍在努力進行一些微調，但我認為，對商業方面和關鍵資產的關注已經帶來了很多清晰度，因此，我們看到了良好的接受度。正如 Vas 所提到的，我們預計這不會放緩太多。

And one of the last element, the efficiency and productivity you're seeing, the leverage, it's in part because of the streamlining of the organization from a headcount, but also that focus leads to much more efficient resource allocation and the elimination of unnecessary spend in many areas. And I think that additional productivity is what you're seeing flow through the pipeline when you look at the core operating income performance and the margin expansion within the Innovative Medicines business. Next question, operator?

最後一個要素，你所看到的效率和生產力，槓桿，部分是因為組織從人數上精簡，而且這種專注導致更有效的資源分配和消除不必要的支出在許多領域。而且我認為，當您查看創新藥物業務的核心營業收入表現和利潤率擴張時，您會看到流經管道的額外生產力。下一個問題，運營商？

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

你的下一個問題來自古根海姆證券公司的 Seamus Fernandez。

So just hoping that we could get a little bit of color on one of your key assets, your BTK for CSU and which is studying NMS as well. Vas, maybe if you could just tell us how confident you are that your asset can avoid the liver safety pitfalls that have plagued this class of agents in MS at a minimum, have we seen enough patients exposures to kind of move past that seemingly 70-day time point that FDA has been raising concerns about against 2 other assets?

因此，希望我們能對您的一項關鍵資產，即 CSU 的 BTK 以及也在研究 NMS 的 BTK 有所了解。 Vas，也許如果你能告訴我們你有多大信心你的資產至少可以避免困擾 MS 這類藥物的肝臟安全隱患，我們是否已經看到足夠多的患者接觸超過看似 70- FDA 一直在對其他 2 項資產提出擔憂的時間點？

Yes. Thanks, Seamus. So we have the detailed monitoring in place, which FDA has asked for. We have 1,600 patients exposed across dose levels. We have not seen to deliver toxicity or liver signals that others have seen, I think coming back to the science, again, BTK is not expressed in the liver. Importantly, patients who genetically don't express BTK also don't have liver abnormalities.

是的。謝謝，西默斯。因此，我們進行了詳細的監控，這是 FDA 要求的。我們有 1,600 名不同劑量水平的患者。我們還沒有看到傳遞其他人看到的毒性或肝臟信號，我認為回到科學，再次，BTK 不在肝臟中表達。重要的是，基因上不表達 BTK 的患者也沒有肝臟異常。

And from what everything we could see in our preclinical work, the structure of our molecule didn't generate any metabolites or other off-target liver effects within preclinical models. So we believe this is related to the structures of the medicines, not actually the BTK as a target. And our hope is we can demonstrate that through the CSU 2 ongoing studies and the 2 MS studies. But ultimately, this will, of course, be data-driven.

從我們在臨床前工作中看到的一切來看，我們的分子結構在臨床前模型中沒有產生任何代謝物或其他脫靶肝臟效應。所以我們認為這與藥物的結構有關，實際上與作為靶標的 BTK 無關。我們希望我們可以通過 CSU 2 正在進行的研究和 2 MS 研究證明這一點。但最終，這當然是數據驅動的。

But I believe that if we can demonstrate that there's strong mechanistic reasons why there should not be class labeling and really specific to the individual molecules. And I believe in prior slides, we've -- my [recollection] is we showed the structures of the 4 BTK inhibitors and prior R&D days. And you would notice that our BTK inhibitor has a very unique structure relative to the other 3. Our hope is that it can drive a better safety profile, but we'll ultimately see based on the clinical data that we generate. Next question, operator?

但我相信，如果我們能夠證明有很強的機械原因為什麼不應該有類別標籤並且真正針對單個分子。我相信在之前的幻燈片中，我們已經——我的[回憶]是我們展示了 4 種 BTK 抑製劑的結構和之前的研發日。你會注意到我們的 BTK 抑製劑相對於其他 3 種抑製劑具有非常獨特的結構。我們希望它能夠帶來更好的安全性，但我們最終會根據我們生成的臨床數據看到。下一個問題，運營商？

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

您的下一個問題來自 Stifel 的 Eric Le Berrigaud。

Two questions, Pluvicto related, please. The first on your slide, Vas, the footnote says that the [250,000] doses per annum will be achieved across all RLTs is then included, could you mention how many doses currently are supplied for Lutathera today so that we can deduct how much is left for Pluvicto. And the second question, in terms of capacities yet to come and the split between the different sites, would it be a great and a fair assumption to say that Millburn once all lines are approved and operational will be of the same size of the Brio in Italy and that Indianapolis will be maybe the largest one, representing more than 50%. And also, could you repeat that Asia is not part of the 250,000 doses and we'll have to come on top.

有兩個問題，Pluvicto 相關，請。 Vas，你幻燈片上的第一個，腳註說所有 RLT 每年將達到 [250,000] 劑，然後包括在內，你能否提及目前為 Lutathera 提供了多少劑，以便我們可以扣除剩餘的劑量對於 Pluvicto。第二個問題，就即將到來的產能和不同站點之間的分配而言，如果說 Millburn 一旦所有生產線都獲得批准並投入運營，其規模將與 Brio 在意大利和印第安納波利斯可能是最大的一個，佔 50% 以上。另外，你能否重複一遍，亞洲不在 250,000 劑疫苗之列，我們必須排在首位。

So a multipart question, I'll try to take them off one by one. So Lutathera is a very small volume product. So it's not a meaningful contributor. So I don't think it would have a big -- I don't know the exact number, but I don't think it will have a meaningful impact on the 250,000 dose target. Roughly speaking, when Millburn is fully online, it would more than double the capacity over Ivrea standalone. And as we, of course, get that site fully ramped up, it could do potentially even more. But I think as a base case assumption, Millburn doubles our capacity versus Ivrea. Indianapolis is a much larger scale facility with those semi-automated and automated lines, which when running at full scale a few years from now would have significant capacity but it would add significant -- it would be a larger site than either Millburn or Ivrea in terms of the capacity it could generate.

所以這是一個多部分的問題，我將嘗試將它們一一解開。所以 Lutathera 是一種體積非常小的產品。所以它不是一個有意義的貢獻者。所以我認為它不會有很大的——我不知道確切的數字，但我認為它不會對 250,000 劑量目標產生有意義的影響。粗略地說，當 Millburn 完全在線時，它的容量將比獨立的 Ivrea 增加一倍以上。當然，隨著我們全面提升該站點，它可能會做得更多。但我認為，作為一個基本案例假設，與伊夫雷亞相比，米爾本的產能翻了一番。印第安納波利斯是一個規模大得多的設施，擁有那些半自動和自動生產線，當這些生產線在幾年後全面運行時將具有顯著的容量，但它會顯著增加——它將比米爾本或伊夫雷亞的站點更大就其可以產生的能力而言。

So taken together, those 3 sites, obviously, have a lot of production capacity for Pluvicto and, of course, Lutathera. Lutathera is not a production issue for us. Now in terms of the ex U.S., we currently would plan to supply the ex U.S. from Ivrea and Zaragoza outside of Europe, outside of the U.S. So Asian markets, but we have plans in place to put up greenfield facilities in Asian markets. We've not disclosed exactly. But certainly, Japan is high in our mind amongst others to put forward those greenfield facilities to add capacity in Asia, particularly given the strong interest we've seen in Japan, Singapore and other markets for Pluvicto. Next question, operator?

因此，這三個地點加在一起，顯然對 Pluvicto 和 Lutathera 都有很大的生產能力。 Lutathera 對我們來說不是生產問題。現在就前美國而言，我們目前計劃從歐洲以外的伊夫雷亞和薩拉戈薩、美國以外的亞洲市場供應前美國，但我們計劃在亞洲市場建立綠地設施。具體我們沒有透露。但可以肯定的是，日本非常希望在其他國家中提出這些綠地設施以增加亞洲的產能，特別是考慮到我們在日本、新加坡和其他市場對 Pluvicto 表現出濃厚的興趣。下一個問題，運營商？

Your next question comes from the line of Michael Leuchten from UBS.

你的下一個問題來自瑞銀的 Michael Leuchten。

Question for Harry, please. Going back to Slide 27. There's a lot of pluses and not that many minuses and obviously, Q1, the performance was very good. But your guidance increase seems a little bit modest in relative -- in relation to that. So just wondering, as we think about phasing over the quarters, like what is it in the rest of the year that we should keep an eye on beyond the integration costs or the separation costs for Sandoz?

請向哈利提問。回到幻燈片 27。優點很多，缺點不多，顯然，Q1 的表現非常好。但相對於此，你的指導增加似乎有點適度。所以只是想知道，當我們考慮分階段結束這些季度時，除了 Sandoz 的整合成本或分離成本之外，我們應該關註今年剩餘時間的什麼？

Yes. Thank you, Michael. I mean, we do have to note that on the bottom line, we upgraded to notches. So I think that's not too small for quarter 1 update, clearly shows our confidence in the future. Now the one thing we have to watch a bit is inflation. That's where we have to see. When you think about it, right, the inflation on the cost of goods, actually, the products we sell now are from an inventory produced in the second half of last year, right? So the products we produce now will be sold in the second half of this year, right, with a huge standard cost approach and so on.

是的。謝謝你，邁克爾。我的意思是，我們確實必須注意到，在底線，我們升級到了缺口。所以我認為這對於第一季度的更新來說並不算太小，清楚地表明了我們對未來的信心。現在我們必須注意的一件事是通貨膨脹。這就是我們必須看到的地方。你想一想，對吧，商品成本的膨脹，其實我們現在賣的產品，是去年下半年生產的存貨，對不對？所以我們現在生產的產品，今年下半年要賣，對吧，用巨額的標準成本法等等。

It's not a super big deal, but overall, we expect another $500 million of inflation after having $350 million last year. Again, our productivity efforts are expected to much more than offset. But given the large part of the Sandoz as part of the total COGS, right? That hits them a bit over proportionately. But it's something we have to watch as we go forward. And that's why it's the first of the 3 negatives, if you will.

這不是什麼大不了的事，但總的來說，我們預計在去年有 3.5 億美元之後還會有 5 億美元的通貨膨脹。同樣，我們的生產力努力預計將遠遠超過抵消。但是考慮到 Sandoz 的很大一部分是總 COGS 的一部分，對嗎？這對他們的打擊有點過分了。但這是我們前進時必須注意的事情。這就是為什麼它是 3 個底片中的第一個，如果你願意的話。

I mean when you look at our top line, you feel like there's no generics, there is generic impact as we speak, right? (inaudible) some of you pointed out, there's a miss on Gilenya. I mean we take -- I would always assume normal modeling on the small molecule generics, right? It goes extremely fast in U.S. and still outside of U.S., a bit slower. And of course, we are holding some of the IP in Europe, in some European countries, but still no centers in Europe, we haven't seen the most massive effect. But I think I don't want to overtalk it too much. I mean, we are upgrading to high single digits, low double digits, right? So certainly, the green plus is by far outweigh the red minuses.

我的意思是，當您查看我們的頂線時，您會覺得沒有仿製藥，就像我們所說的那樣具有仿製藥的影響，對嗎？ （聽不清）你們中的一些人指出，Gilenya 有失誤。我的意思是我們採取 - 我總是假設對小分子仿製藥進行正常建模，對嗎？它在美國的速度非常快，但在美國以外的地方，速度要慢一些。當然，我們在歐洲，在一些歐洲國家擁有一些知識產權，但在歐洲仍然沒有中心，我們還沒有看到最巨大的影響。但我想我不想說太多。我的意思是，我們正在升級到高個位數，低兩位數，對嗎？所以可以肯定的是，綠色加號遠遠超過紅色減號。

Next question, operator?

下一個問題，運營商？

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

你的下一個問題來自花旗銀行的 Andrew Baum。

Please forgive the voice. I'm struggling with COVID. A question for Vas, suspect you remember, historically, I've described the (inaudible) syndrome in always being the early adopter and taking a less risk relative to peers. We're going to completely contradict myself. The early data from SET with CAR T CD-19 in refractory autoimmune is remarkable. The biology is strong, patient access node patients is much easier in oncology. We understand that Bristol is about to open a very large program with their CAR T in lupus and multiple other autoimmune diseases. When I look at Novartis, the trial that's posted that's just opened has got a sum of 12 patients. So this 12 patients just to start, and it's materially going to expand? Or is there some risk that the pendulum is overcorrected and Novartis risk missing out on a major commercial opportunity.

請原諒聲音。我正在與 COVID 作鬥爭。 Vas 的一個問題，懷疑你還記得，從歷史上看，我已經描述了（聽不清）綜合症，即始終是早期採用者並且相對於同齡人承擔的風險較小。我們將完全自相矛盾。使用 CAR T CD-19 治療難治性自身免疫的早期數據非常顯著。生物學性強，患者進入結點患者在腫瘤學中要容易得多。我們知道 Bristol 即將啟動一個非常大的項目，用他們的 CAR T 治療狼瘡和其他多種自身免疫性疾病。當我看諾華公司時，剛剛發布的試驗有 12 名患者。那麼這 12 名患者才剛剛開始，它會在實質上擴大嗎？或者是否存在鐘擺矯枉過正的風險，諾華（Novartis）可能會錯失重要的商業機會。

Yes. Thanks, Andrew. So we're very excited about the potential of CAR therapy in immunology. We believe with YCB, perhaps unlike our competitors, we have a low-cost rapid manufacturing process with hopefully better safety profile and much more scalable, particularly for the immunology indications. I don't know where the competitive set is on that technology. We've opened up an initial program in SLE. We plan to expand that across a range of other immunology indications. Once we have the initial data set that regulators have asked for us before safety data, before we can make an expansion cohort across multiple immunology. So those protocols are all written I -- this is our top priority for CAR therapy.

是的。謝謝，安德魯。所以我們對 CAR 療法在免疫學中的潛力感到非常興奮。我們相信，與 YCB 相比，也許與我們的競爭對手不同，我們擁有低成本的快速製造工藝，希望具有更好的安全性和更具可擴展性，特別是對於免疫學適應症。我不知道該技術的競爭格局在哪裡。我們已經在 SLE 中打開了一個初始程序。我們計劃將其擴展到一系列其他免疫學適應症。一旦我們獲得了監管機構在安全數據之前要求我們提供的初始數據集，我們就可以跨多種免疫學進行擴展隊列。所以這些協議都是我寫的——這是我們 CAR 治療的首要任務。

I mean we are putting immunology ahead of DLBCL and multiple myeloma, our CAR teams are working around the clock now to expand as fast as we can given the very powerful case reports that we've seen out of Germany and other jurisdictions. I've read those case reports myself, and I would agree with you, it's pretty remarkable to see what you can do with a full reset of the B-cell compartment, B cells come back, but you don't have B-cell lineages that seems to target these self-antigens that lead to these diseases. So full team ahead, it's going to be a race, we accept that, but we want to go as big and broad as we can given our long history in immunology. And we believe versus the 2 peers, given our experience running trials in immunology that should give us an advantage if we execute well. Next question, operator?

我的意思是我們將免疫學置於 DLBCL 和多發性骨髓瘤之前，我們的 CAR 團隊現在正在全天候工作，以盡可能快地擴大我們在德國和其他司法管轄區看到的非常強大的案例報告。我自己讀過那些病例報告，我同意你的看法，看到完全重置 B 細胞隔室可以做什麼，B 細胞回來，但你沒有 B 細胞，這是非常了不起的譜系似乎以導致這些疾病的這些自身抗原為目標。如此完整的團隊領先，這將是一場比賽，我們接受這一點，但鑑於我們在免疫學領域的悠久歷史，我們希望盡可能大和廣泛。我們相信與 2 個同行相比，鑑於我們在免疫學方面進行試驗的經驗，如果我們執行得好，這應該會給我們帶來優勢。下一個問題，運營商？

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

你的下一個問題來自美國銀行的 Graham Parry。

I just wanted to just follow up on conference presentation. So naturally, I think you haven't ruled out ASCO, but I think the headline -- or the release -- the titles will be released tomorrow. So if it's not in those cycles, is it possible still that it could be at ASCO? And I notice you are going to do an ASCO event, is that with the intent to discuss NATALEE. And then for Pluvicto, he PSMAfore, do you think you'll be able to hit the ESMO conference? Or can you confirm now that you wouldn't make that conference with that data?

我只想跟進會議介紹。所以很自然地，我認為你沒有排除 ASCO，但我認為標題——或發布——標題將在明天發布。因此，如果它不在那些週期中，它是否還有可能出現在 ASCO 中？我注意到您將要舉辦 ASCO 活動，目的是討論 NATALEE。然後對於 Pluvicto，他 PSMAfore，你認為你能參加 ESMO 會議嗎？或者你現在可以確認你不會用這些數據召開會議嗎？

Yes. So I think on NATALEE, I'd say I can't comment on the specific conferences that we are putting forward. But we're obviously moving as fast as we can to get NATALEE out into the public. So it can be obviously reviewed by investigators, clinicians and of course, the investment community. So I'll leave it at that on that, NATALEE.

是的。所以我認為關於 NATALEE，我想說我不能對我們提出的具體會議發表評論。但我們顯然正在盡可能快地讓 NATALEE 進入公眾視野。因此，研究人員、臨床醫生，當然還有投資界顯然可以對其進行審查。所以我就此打住，NATALEE。

On Pluvicto, it's too soon to say. We have had discussions with FDA, and FDA has made clear the information fraction that they want in terms of the number of OS events. So we're just waiting to hit that, that number will lock. And then as soon as we lock and have the data, we'll move forward to a Congress as fast as we can. We're hopeful that can happen in the first part of the summer, but it's all data dependent. And until we have the events, we obviously can't make the lock at FDA. But I would say the guidance we received from FDA is fully in line with the guidance that our competitors received as well in December. AstraZenica received, I think, very similar guidance for their prostate cancer medicine. Next question, operator.

關於 Pluvicto，現在下結論還為時過早。我們已經與 FDA 進行了討論，並且 FDA 已經明確了他們在 OS 事件數量方面想要的信息部分。所以我們只是在等待擊中那個數字，這個數字將被鎖定。然後，一旦我們鎖定並獲得數據，我們就會盡快召開國會。我們希望這能在夏季的第一部分發生，但這完全取決於數據。在我們有這些事件之前，我們顯然無法在 FDA 鎖定。但我要說的是，我們從 FDA 收到的指南與我們的競爭對手在 12 月份收到的指南完全一致。我認為，阿斯利康 (AstraZenica) 對其前列腺癌藥物的指導非常相似。下一個問題，接線員。

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

你的下一個問題來自法國巴黎銀行的理查德帕克斯。

And just to follow on from Michael's question over the guidance. It's obviously a very impressive margin performance in IM in Q1, but guidance doesn't seem to suggest that's not sustained at that level of year-on-year basis point improvement through the year. So I just wondered if you could talk again about phasing benefits that might have been in Q1 how Innovative Medicine margins should evolve or I know you talked about inflationary impacts on COGS, but that sounds like that's more impacting Sandoz. So yes, any insight helpful.

只是為了繼續邁克爾關於指導的問題。顯然，第一季度 IM 的利潤率表現令人印象深刻，但指引似乎並未表明這一點在全年的同比基點改善水平上沒有持續。所以我只是想知道你是否可以再次談論第一季度創新醫學利潤率應該如何演變的分階段收益，或者我知道你談到了通貨膨脹對 COGS 的影響，但這聽起來對 Sandoz 的影響更大。所以是的，任何見解都有幫助。

Thank you, Richard. Actually, I don't think I can say so much more. I mean, quarterly margins, as you know, they are not as linear, right? You have the improvement in Q1. We cannot just multiply that or assume that is happening each quarter now. But overall, we are, of course, highly confident in margin improvement on the year. It's actually also quite significant if you model it out, and then the inflation we have to watch altogether, right? I mean that's not -- it's not only hitting on bundles. It's also hitting on innovative medicines. It's just not as big there for the overall P&L, right?

謝謝你，理查德。其實，我想我不能說那麼多了。我的意思是，如你所知，季度利潤率不是線性的，對吧？你在第一季度有了改進。我們不能只是乘以它或假設現在每個季度都在發生這種情況。但總的來說，我們當然對今年的利潤率改善充滿信心。如果你把它建模出來，它實際上也很重要，然後我們必須一起觀察通貨膨脹，對吧？我的意思是那不是 - 它不僅是捆綁銷售。它也在打擊創新藥物。對於整體損益而言，它並沒有那麼大，對吧？

So I would just -- let's be a little bit cautious after 3 months, I would continue to expect good productivity in top line, how exactly the margin by, we also -- I don't believe in quarterly guidance, be it on sales or margin, right, it is too much. We have dynamics. We always want to ensure we do the right investments on everything. And -- but I would expect a very good further dynamic margin development as we go forward. As I also expect the top line and productivity programs to further positively develop. But this is a very high margin improvement in 1 quarter and I would not suggest to simply assume that for the rest of the year.

所以我只是 - 讓我們在 3 個月後有點謹慎，我會繼續期待良好的生產率，利潤率究竟如何，我們也 - 我不相信季度指導，無論是在銷售方面或保證金，對，太多了。我們有動力。我們始終希望確保我們對所有事情都進行了正確的投資。而且 - 但我希望隨著我們的前進，會有一個非常好的動態利潤率發展。正如我還期望的那樣，頂線和生產力計劃將進一步積極發展。但這是 1 個季度的非常高的利潤率改善，我不建議在今年餘下時間簡單地假設這一點。

Next question, operator?

下一個問題，運營商？

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

您的下一個問題來自 Cowen 的 Stephen Scala。

I'm curious if Novartis has any more visibility on the profile of MBL-949 for obesity, on the Q4 call, you said that you would have greater visibility on dosing schedule in the second quarter. I'm curious if the data is in-house, and I'm wondering why Novartis rarely mentions this product, particularly given the global focus on obesity.

我很好奇 Novartis 是否對 MBL-949 的肥胖概況有更多的了解，在第四季度的電話會議上，你說你會在第二季度對給藥時間表有更大的了解。我很好奇數據是否在內部，我想知道為什麼諾華公司很少提及該產品，特別是考慮到全球都在關注肥胖問題。

Yes. Thanks, Steve. Just looking at my colleagues. So the answer is we don't have the data set yet, but we will have it in the coming period. And then we'll update accordingly. I think our reluctance is just to -- we want to be sure we have a real medicine here because I think given the overall euphoria, I guess, around obesity, we don't want to create any some of false, so we want to make sure that this is -- if it is a real drug and if not, we'll close to disclose it that way as well. So as soon as we have a clear understanding of did we adequately navigate the safety and efficacy profile for this medicine. We'll update you accordingly. Next question, operator?

是的。謝謝，史蒂夫。只是看著我的同事。所以答案是我們還沒有數據集，但我們將在未來一段時間內擁有它。然後我們會相應地更新。我認為我們的不情願只是——我們想確保我們在這裡有一種真正的藥物，因為我認為鑑於整體的欣快感，我想，圍繞肥胖，我們不想製造任何虛假的東西，所以我們想確保這是 - 如果它是一種真正的藥物，如果不是，我們也會以這種方式關閉它。因此，一旦我們清楚地了解了我們是否充分了解了該藥物的安全性和有效性概況。我們會相應地更新你。下一個問題，運營商？

We will now take our last question for today. And the question comes from the line of Matthew Weston from Credit Suisse. Matthew. Are you on mute?

我們現在將回答今天的最後一個問題。問題來自瑞士信貸的 Matthew Weston。馬修。你在靜音嗎？

Can you hear me? I apologize. You'd have thought for a couple of years of COVID, I would have figured it out. It's a slightly odd question about contract manufacturing, actually. You've now taken the biologics contract manufacturing out of Sandoz, and it's a relatively meaningful quarterly revenue number growing strongly. I also noted that you recently took on, I think, a contract manufacturing contract for CAR T from Bristol and Legend. I'd just be very interested to understand whether it's a strategic part of the Novartis business and you're trying to fill excess capacity across the network that you have or whether it remains more just sort of an ad hoc and opportunistic affair? And how big could it be, Harry? Could it be a $1 billion business for Novartis over time or more?

你能聽到我嗎？我道歉。你會考慮 COVID 幾年，我會想出來的。實際上，這是一個關於合同製造的有點奇怪的問題。你現在已經將生物製劑合同製造從 Sandoz 中剝離出來，這是一個相對有意義的季度收入增長強勁的數字。我還注意到，我認為你最近從 Bristol 和 Legend 獲得了 CAR T 的合同製造合同。我只是很想知道它是否是諾華公司業務的戰略部分，你正試圖填補你擁有的網絡中的過剩產能，還是它仍然更像是一種臨時和機會主義的事情？它有多大，哈利？隨著時間的推移或更長時間，這對諾華公司來說可能是一項價值 10 億美元的業務嗎？

So I'll start with the strategic side, and then Harry can comment on the financial outlook. It is strategic. When you look at our investments over the last 5 years in advanced therapy platforms, we built up quite a bit of know-how. We believe we're one of the largest producers of AAV gene therapies in the world. One of the largest producers of CAR therapies using lentiviral technologies in the world through the pandemic. We began a major producer of plasmids, also a producer of mRNA through Leqvio, we will soon be the largest producer of siRNAs through our facility here in Switzerland through the capacity expenses, particularly with automated lines with RLT, we will likely or surely be the largest producer of RLTs in the world. And so the opportunity exists when appropriate competitively to leverage that manufacturing base to generate a high-margin business for the company, and that's why we moved it over. It will build over time, not overnight, but it certainly was a strategic consideration to move it in this direction. Harry?

所以我將從戰略方面開始，然後 Harry 可以評論財務前景。這是戰略性的。看看過去 5 年我們在先進治療平台上的投資，我們積累了相當多的專業知識。我們相信我們是世界上最大的 AAV 基因療法生產商之一。通過大流行，世界上使用慢病毒技術的 CAR 療法的最大生產商之一。我們開始成為質粒的主要生產商，也是通過 Leqvio 生產 mRNA 的主要生產商，我們很快將通過我們在瑞士的設施成為最大的 siRNA 生產商，通過產能支出，特別是帶有 RLT 的自動化生產線，我們很可能或肯定會成為最大的 siRNA 生產商世界上最大的 RLT 生產商。因此，在適當的時候存在機會，可以利用該製造基地為公司創造高利潤業務，這就是我們將其轉移的原因。它會隨著時間的推移而建立，而不是一夜之間，但將其朝這個方向發展肯定是一種戰略考慮。哈利？

Yes, Matthew, I would call it, it's a mix of strategic and opportunistic. We have very good capacities, our production manufacturing teams are doing a great job increasing yields. So also, our cost of goods are very competitive. Of course, in terms of priority first is the Innovative Medicine strategy as well as the Sandoz biosimilars, right, with which the future Sandoz will have very clear contractual obligations.

是的，馬修，我會這樣稱呼它，它是戰略性和機會主義的結合。我們有很好的能力，我們的生產製造團隊在提高產量方面做得很好。因此，我們的商品成本也非常有競爭力。當然，就優先級而言，首先是創新醫學戰略以及山德士生物仿製藥，對，未來山德士將與之有非常明確的合同義務。

And then, of course, if there's capacity available, again, with contractual obligations, we will leverage further. And we do have further capacities. And that's -- so at the moment, when you look at it, we had a run rate $0.5 billion, if I recall correctly, right, it's growing. So your $1 billion is not too far away over the years. right? So that could be a meaningful contribution. Of course, not like a big product, a big brand, but very important in terms of further maximizing our capacity as well as nice delivery to the bottom line.

然後，當然，如果有可用的能力，同樣，有合同義務，我們將進一步利用。我們確實有更多的能力。那就是 - 所以目前，當你看它時，我們的運行率為 5 億美元，如果我沒記錯的話，它正在增長。因此，這些年來您的 10 億美元並不算太遠。正確的？所以這可能是一個有意義的貢獻。當然，這不像一個大產品、一個大品牌，但在進一步最大化我們的能力以及良好的交付至底線方面非常重要。

Very good. So thank you all for joining today's conference call. I really appreciate the interest in Novartis. We look forward to continuing to deliver over the course of this year and keeping you all updated as we progress. And we wish you a great week. Thank you.

非常好。感謝大家參加今天的電話會議。我非常感謝對諾華的興趣。我們期待在今年繼續交付，並隨著我們的進展讓大家了解最新情況。我們祝你度過愉快的一周。謝謝。

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

謝謝。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。