Novartis AG (NVS) 2022 Q4 法說會逐字稿

Good morning and good afternoon, and welcome to the Novartis Q4 2022 Results Release Conference Call and Live Webcast. (Operator Instructions) And the conference is being recorded. (Operator Instructions) A recording of the conference, 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 2022 年第四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）電話會議結束後不久，將在我們的網站上提供會議錄音，包括問答環節。

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。

And thank you very much, operator. And thank you to everybody for participating on what is a very busy day for reporting in pharma, European pharma.

非常感謝你，接線員。並感謝大家參加歐洲製藥公司非常忙碌的報告日。

Before we start, just reading the safe harbor statement. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. For a description of some of these factors, please refer to the company's Form 20-F and its most recent quarterly results on Form 6-K that respectively were filed with and furnished to the U.S. Securities and Exchange Commission.

在我們開始之前，請先閱讀安全港聲明。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。有關其中一些因素的說明，請參閱公司分別向美國證券交易委員會備案並提供的 20-F 表及其最近的 6-K 表季度業績。

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

然後，我將交給 Vas。

Thanks, Samir, and thanks, everyone, for joining today's conference call. I really appreciate your interest in the company and our update for the full year 2022.

謝謝薩米爾，也謝謝大家參加今天的電話會議。非常感謝您對公司的關注以及我們 2022 年全年的更新。

If we move to Slide 4, this year, as you saw in our earnings release on 2022, we delivered what we believe is really robust core operating income growth and margin expansion. From a sales standpoint, you saw Q4 sales up 3%, with IM delivering Q4 sales at 3% (inaudible) Sandoz sales.

如果我們今年轉到幻燈片 4，正如您在我們 2022 年的收益發布中看到的那樣，我們實現了我們認為真正強勁的核心營業收入增長和利潤率擴張。從銷售的角度來看，您看到第四季度銷售額增長了 3%，而 IM 提供的第四季度銷售額為 Sandoz 銷售額的 3%（聽不清）。

Productivity standpoint, we had a 15% core operating income growth in quarter 4, and Harry will go a little bit further through the dynamics that drove that.

從生產力的角度來看，我們在第 4 季度的核心營業收入增長了 15%，Harry 將進一步探討推動這一增長的動力。

But for the full year, that led to 8% core operating income growth ahead of our guidance. And that leads us to have now a margin, for IM in quarter 4, of 36.4%, and on the full year, 36.9%. And as a reminder, taken together, inclusive of corporate costs, we are well on our way now towards our 40% core margin guidance for the medium term.

但就全年而言，這導致核心營業收入增長 8%，超出了我們的指導。這導致我們現在的 IM 第 4 季度利潤率為 36.4%，全年為 36.9%。提醒一下，包括企業成本在內，我們現在正朝著中期 40% 的核心利潤率指導目標邁進。

Now in terms of innovation, some important milestones, we'll go through those in a bit more detail. And we continue our journey on ESG sustainability-linked bond. We continue to progress towards our 2025 targets. We had 31 million patients in our Novartis flagship programs, and we continue to have solid ratings across the key ESG rating agencies.

現在，在創新方面，一些重要的里程碑，我們將更詳細地介紹這些。我們將繼續我們的 ESG 可持續發展相關債券之旅。我們繼續朝著 2025 年的目標前進。我們的諾華旗艦項目有 3100 萬患者，我們繼續在主要 ESG 評級機構中獲得可靠的評級。

Now moving to Slide 5. You'll remember that in September at our Meet the Management, we rolled out our new focused strategy, and we've been diligently been implementing this across the company: 5 core therapeutic areas, 2 plus 3 technology platforms, 4 priority geographies, a mindset to really focus on high-value medicines to accelerate growth, delivering the return profile we believe the company can achieve, and you saw that already in quarter 4 and a continued commitment to culture, data science and building trust with society.

現在轉到幻燈片 5。您會記得在 9 月份的管理層會面中，我們推出了新的重點戰略，我們一直在全公司範圍內努力實施這一戰略：5 個核心治療領域，2 加 3 個技術平台, 4 個優先地區，真正專注於高價值藥物以加速增長的心態，提供我們相信公司可以實現的回報狀況，你已經在第四季度看到了這一點，並繼續致力於文化、數據科學和建立信任與社會。

Now moving to Slide 6. And as a reminder, as you all well know, over the last 5 years and really over since 2014, we've been on a journey to really focus Novartis as a pure-play innovative medicines company. And through a number of actions we've taken, most recently with the announced planned spin-off with Sandoz, we're on our way to becoming a 100% innovative medicines company.

現在轉到幻燈片 6。提醒大家，眾所周知，在過去的 5 年中以及自 2014 年以來，我們一直在努力將諾華公司真正定位為一家純粹的創新藥物公司。通過我們採取的一系列行動，最近宣布了與 Sandoz 的分拆計劃，我們正朝著成為 100% 創新藥物公司的方向邁進。

And when you look at the right-hand side of the slide, we believe that a simplified organizational model will allow us to have greater focus, leverage our scale and really uniquely position us as a global pure-play, large-scale innovative pharma company versus our peer set. And over time, hopefully, also re-rate the company given the growth profile we intend to deliver.

當您查看幻燈片的右側時，我們相信簡化的組織模型將使我們能夠更加專注，利用我們的規模並真正將我們定位為一家全球性的大型創新製藥公司與我們的同行相比。隨著時間的推移，希望根據我們打算提供的增長情況重新評估公司。

Now moving to Slide 7. We've also guided to improve financials with this new focused company, with 4% sales growth; a goal of core operating income margin of 40%, as I previously stated; continued improvement on free cash flow; and importantly, an improving and attractive return on invested capital profile. That will allow us to continue to invest across our capital allocation priorities, which Harry will go through in a bit more detail later on in the presentation.

現在轉到幻燈片 7。我們還指導這家新的重點公司改善財務狀況，銷售額增長 4%；正如我之前所說，核心營業利潤率為 40% 的目標；自由現金流持續改善；重要的是，投資資本狀況的改善和有吸引力的回報。這將使我們能夠繼續投資於我們的資本分配優先事項，Harry 將在稍後的演講中更詳細地介紹這一點。

Now moving to Slide 8. In each of the 5 therapeutic areas that we've outlined, we have core large-scale commercial assets and have multiple pipeline assets that are now progressing. And we focused our R&D organization around these 5 areas. We're streamlining the pipeline. I think you'll see over the coming quarters us exiting additional assets as we really try to prune out non-core areas, and put all of our scientific firepower and ingenuity towards building out a deep set of pipeline assets in each of these therapeutic areas. We'll look forward to showing that progress over the coming year.

現在轉到幻燈片 8。在我們概述的 5 個治療領域中的每一個領域，我們都有核心的大型商業資產，並且有多個正在開發中的管道資產。我們將研發組織集中在這 5 個領域。我們正在簡化管道。我想你會在接下來的幾個季度看到我們退出額外的資產，因為我們真的試圖修剪掉非核心領域，並將我們所有的科學火力和獨創性用於在這些治療領域中的每一個領域建立一套深入的管道資產.我們期待在來年展示這一進展。

Then moving to Slide 9. In terms of capital allocation priorities and the strong balance sheet that we have, continue to invest in the organic business and pursue value-creating bolt-on, we look at the full range of M&A possibilities, but our focus is on sub-$5 billion assets, where we believe we have the opportunity to generate strong returns and find the most value when we look at M&A opportunities.

然後轉到幻燈片 9。在資本分配優先事項和我們擁有的強大資產負債表方面，繼續投資於有機業務並追求創造價值的補強，我們著眼於全方位的併購可能性，但我們的重點擁有低於 50 億美元的資產，我們相信我們有機會在尋找併購機會時產生可觀的回報並找到最大的價值。

And we also remain committed to our growing our annual dividend, and Harry will outline that in a little while. But we have paid out $7.5 billion in 2022. Our proposed dividend is another growth in the 3.2% Swiss franc and 3.9% U.S. dollar range. And even after the proposed Sandoz spin-off, there will be no re-basing of that dividend. We'll continue to grow off of the current base. And we're continuing to implement our $15 billion share buyback program. We have $4.9 billion still to be executed. And we'll continue to look at doing additional share buybacks over the coming years when the opportunities present themselves.

我們也將繼續致力於增加我們的年度股息，Harry 將在稍後概述這一點。但我們在 2022 年支付了 75 億美元。我們提議的股息是在 3.2% 瑞士法郎和 3.9% 美元範圍內的又一次增長。即使在擬議的 Sandoz 分拆之後，該股息也不會重新調整。我們將繼續在目前的基礎上發展壯大。我們將繼續實施 150 億美元的股票回購計劃。我們還有 49 億美元需要執行。當機會出現時，我們將繼續考慮在未來幾年進行更多的股票回購。

Now moving to Slide 10. And I want to turn now to our innovation story and where we are and continuing to improve our overall R&D productivity. I think it's been well recognized, we are a leader in terms of generating approvals, the leading company over the last 20-plus years in generating drug approvals in the United States and around the world. Our focus now is to improve the value per asset, identifying assets earlier that have significant potential, investing in those assets more aggressively, pursuing more life cycle management indications.

現在轉到幻燈片 10。現在我想談談我們的創新故事以及我們所處的位置，並繼續提高我們的整體研發生產力。我認為這是公認的，我們在獲得批准方面處於領先地位，是過去 20 多年在美國和世界範圍內獲得藥品批准的領先公司。我們現在的重點是提高每項資產的價值，更早地識別具有巨大潛力的資產，更積極地投資這些資產，尋求更多的生命週期管理指標。

And with that, a goal to increase the success rate and reduce the cycle times and generate larger assets. Maybe not winning the game of generating the most assets, but really focused on high-value, high-impact medicines that could impact patients and the company's financial performance.

因此，目標是提高成功率、縮短週期時間並產生更大的資產。也許沒有贏得產生最多資產的遊戲，但真正專注於可能影響患者和公司財務業績的高價值、高影響力的藥物。

Moving to Slide 11. I wanted to walk through some of the readouts that we have coming up in the near term and then in the midterm. Now I think as you all are well aware, Kisqali continues on track. We'll go through this in a bit more detail in a few slides for a readout in the second half. Iptacopan is progressing nicely, with multiple readouts over the course of this year, a planned FDA submission in PNH and then readouts in both IgAN and C3G.

轉到幻燈片 11。我想瀏覽一下我們在近期和中期提出的一些數據。現在我想你們都很清楚，Kisqali 繼續走上正軌。我們將在幾張幻燈片中更詳細地介紹這一點，以便在下半場進行讀出。 Iptacopan 進展順利，今年有多個讀數，計劃在 PNH 中提交 FDA，然後在 IgAN 和 C3G 中讀數。

And then Pluvicto, where we've already read out the top line in the early prostate cancer, early metastatic setting with a planned regulatory submission in the second half. And I'll give you a bit more detail on each of these 3 in a few slides.

然後是 Pluvicto，我們已經讀出了早期前列腺癌的頂線，早期轉移設置，併計劃在下半年提交監管文件。我將在幾張幻燈片中為您詳細介紹這 3 個方面的每一個。

But going to the next slide. When you look at '24, '25, we expect to have an increased pace of readouts of potential multimillion-dollar medicines. Medicines such as pelacarsen in outpatients with elevated Lp(a) level. Ianalumab, where we have now moved this medicine into multiple hematological indications, first and second-line ITP readouts in 2025. We have additional hematology and immunology indications we're pursuing now with this medicine. So you'll see with ianalumab a broad range of Phase III programs initiating over the coming periods.

但是轉到下一張幻燈片。當您查看 24、25 年時，我們預計潛在價值數百萬美元的藥物的讀取速度會加快。 Lp(a) 水平升高的門診患者的藥物，如 pelacarsen。 Ianalumab，我們現在已經將這種藥物轉移到多种血液學適應症，2025 年的一線和二線 ITP 讀數。我們現在正在尋求使用這種藥物的其他血液學和免疫學適應症。因此，您會看到 ianalumab 在未來一段時間內啟動了範圍廣泛的 III 期項目。

Remibrutinib, we have a CSU readout in 2024 ahead of our planned MS readouts in the coming years. And then we continue to progress with -- at OAV-101, which is our gene therapy for SMA in the intrathecal setting, as well as the first-line Scemblix program with a readout planned in 2024.

Remibrutinib，我們在未來幾年計劃的 MS 讀數之前，於 2024 年獲得了 CSU 讀數。然後我們繼續取得進展——在 OAV-101，這是我們在鞘內環境中對 SMA 的基因治療，以及計劃在 2024 年進行讀出的一線 Scemblix 計劃。

Now moving to Slide 13, and going into a bit more detail. NATALEE continues to progress well following the first interim analysis, and we continue to guide to a final readout in the second half of 2023. As a reminder, this is a broad population, including both Stage 2 and Stage 3 patients, so the broadest population study to date. We have longer duration with which we provide therapeutic to patients, 3 versus 2 years, a lower dose to try to improve the overall tolerability profile.

現在轉到幻燈片 13，並進行更詳細的介紹。 NATALEE 在第一次中期分析後繼續取得良好進展，我們將繼續指導 2023 年下半年的最終讀數。提醒一下，這是一個廣泛的人群，包括 2 期和 3 期患者，因此最廣泛的人群研究至今。我們為患者提供治療的持續時間更長，3 年對 2 年，以較低的劑量嘗試改善整體耐受性。

And when you look at where we are in the study, final analysis is expected with 500 iDFS events at the end of 2023. We've completed the first interim analysis as we noted earlier this month, and study continues unchanged. The second interim analysis would happen after 85% of iDFS spends are complete.

當您查看我們在研究中的位置時，預計到 2023 年底將對 500 個 iDFS 事件進行最終分析。我們已經完成了本月早些時候指出的第一個中期分析，並且研究繼續保持不變。第二次中期分析將在 85% 的 iDFS 支出完成後進行。

Now moving to Slide 14. And turning to Pluvicto, where we announced late last year that we demonstrated statistically significant and clinically meaningful radiographic PFS benefits in this patient population. Now we're continuing to follow these patients with the second -- towards the secondary OS endpoint analysis in 2025. We plan -- are on track to file in the second half of this year.

現在轉到幻燈片 14。轉向 Pluvicto，我們在去年年底宣布，我們在該患者群體中展示了具有統計學意義和臨床意義的放射學 PFS 益處。現在，我們將繼續跟踪這些患者的第二個——到 2025 年的次要 OS 終點分析。我們計劃——有望在今年下半年提交文件。

We have had discussions with the FDA and clarify the OS fraction. The fraction of patients that FDA would like to see has reached an OS endpoint prior to filing. We expect to reach that later around the middle of this year, which would then enable the filing in the second half. Now with that guidance from FDA, we've made the decision to hold the publication or presentation of further data until the second half of this year.

我們已經與 FDA 進行了討論，並澄清了 OS 分數。 FDA 希望看到的患者比例在提交前已達到 OS 終點。我們預計將在今年年中晚些時候達到這一目標，屆時將能夠在下半年提交申請。現在，根據 FDA 的指導，我們決定將進一步數據的發布或展示推遲到今年下半年。

I know some of you have been looking for ASCO GU and some of the other congresses in the first half, we will be presenting this data in the second half after we've reached that next threshold that FDA has outlined for us. We have alignment then consistent with what FDA has told to other companies in the prostate cancer space, to then be able to file in the second half with that data set.

我知道你們中的一些人一直在尋找上半年的 ASCO GU 和其他一些大會，我們將在達到 FDA 為我們概述的下一個閾值後，在下半年展示這些數據。然後，我們與 FDA 告知前列腺癌領域其他公司的內容保持一致，然後能夠在下半年使用該數據集提交文件。

Now moving to Slide 15. And why that's so important is, as I'll talk about that when we get to the commercial section of the presentation. Pluvicto is continuing to demonstrate, I think, really impressive uptake in the United States market. And the opportunity is to move first with the PSMAfore study into the pre-taxane setting, which would expand the patient pool from an estimated 27,000 patients to 42,000 patients. Then with the PSMAddition study, which we expect to read out next year, that would expand us further into the hormone-sensitive setting.

現在轉到幻燈片 15。為什麼這如此重要，因為我將在我們進入演示文稿的商業部分時討論這一點。我認為，Pluvicto 正在繼續展示其在美國市場上令人印象深刻的接受度。機會是首先通過 PSMAfore 研究進入紫杉烷前環境，這將使患者群體從估計的 27,000 名患者擴大到 42,000 名患者。然後通過 PSMAddition 研究，我們預計將在明年宣讀，這將使我們進一步進入激素敏感環境。

And then we continue to evaluate how best to pursue Pluvicto further into the biochemical recurrence setting or the localized prostate cancer setting. So stay tuned as we continue to look at the further expansion. But I think this really demonstrates the possibilities of radioligand therapy, and we look forward to continuing to generate a broad set of data to support Pluvicto's use in as many prostate cancer patients that could potentially benefit from the medicine.

然後我們繼續評估如何最好地將 Pluvicto 進一步研究到生化復發環境或局部前列腺癌環境中。因此，請繼續關注我們繼續關注進一步的擴展。但我認為這確實證明了放射配體治療的可能性，我們期待繼續生成廣泛的數據集，以支持 Pluvicto 在盡可能多的可能受益於該藥物的前列腺癌患者中的使用。

Now moving to Slide 16. Turning to iptacopan, and as I noted in the second half of last year, we first provided an update that -- and provided the full data set at ASH, the APPLY data set, which I think showed really outstanding efficacy for all primary -- for both primary and secondary endpoints, superiority to standard of care in patients with residual anemia.

現在轉到幻燈片 16。轉到 iptacopan，正如我在去年下半年指出的那樣，我們首先提供了一個更新——並在 ASH 上提供了完整的數據集，即 APPLY 數據集，我認為它非常出色所有主要終點的療效——主要終點和次要終點均優於殘餘貧血患者的護理標準。

In the Phase III APPOINT study, where we have demonstrated, again, us really strong results, and we'll be presenting that data at a congress in the first half of this year. And then we continue to progress across a range of indications, IgAN and C3G, which will read out in 2023; atypical hemolytic uremic syndrome, where we expect the submission enabling readout in 2025. And then a number of other indications, IC-MPGN, lupus nephritis, immune thrombocytopenia, amongst others.

在 III 期 APPOINT 研究中，我們再次證明了我們非常強大的結果，我們將在今年上半年的一次大會上展示這些數據。然後我們繼續在一系列適應症上取得進展，IgAN 和 C3G，將於 2023 年宣讀；非典型溶血性尿毒症綜合徵，我們預計提交的報告能夠在 2025 年讀出。然後是許多其他適應症，IC-MPGN、狼瘡性腎炎、免疫性血小板減少症等。

Moving to the next slide. And just as a reminder, when you look at the data set that we showed at ASH, I think very impressive data in these patients with residual anemia, some of the notable data when you look at increase in hemoglobin from baseline 51 out of 60 patients versus 0 out of 35, so 82.3% versus 2% against the control arm. Hemoglobin greater than 12, similarly impressive results, 42 out of 60 versus 0 out of 35. Again, transfusion avoidance, you can see an impressive 70.3% improvement and a tenfold lower rate of annualized clinical breakthrough hemolysis.

移動到下一張幻燈片。提醒一下，當你查看我們在 ASH 上展示的數據集時，我認為這些殘留貧血患者的數據非常令人印象深刻，當你查看 60 名患者中有 51 名患者的血紅蛋白較基線增加時，一些值得注意的數據對比 35 人中的 0 人，因此 82.3% 對比對照組的 2%。血紅蛋白大於 12，同樣令人印象深刻的結果，60 人中有 42 人，而 35 人中有 0 人。同樣，避免輸血，您可以看到令人印象深刻的 70.3% 的改善和每年臨床突破性溶血率降低十倍。

So this is in that refractory setting. We'll present the data in the frontline setting. We've also initiated a study of patients who -- to demonstrate we can switch off of the MPC5 directly on to iptacopan in patients in that frontline setting. So building out a broad data package within PNH.

所以這是在那個難處理的環境中。我們將在前線設置中展示數據。我們還啟動了一項針對患者的研究——以證明我們可以在一線環境中將患者的 MPC5 直接關閉到 iptacopan。因此，在 PNH 內構建了一個廣泛的數據包。

Now moving to Slide 18. We wanted to also provide a little more clarity on our approach within IgA nephropathy. In this -- sorry, this is still in PNH, excuse me. So -- and this is the outline of the data set for a point where we'll present this data shortly. And you can see again the design of the study has the potential to be practice-changing in PNH. And as I said, we'll be looking forward to outlining this primary endpoint and secondary endpoint in an upcoming congress.

現在轉到幻燈片 18。我們還想更清楚地說明我們在 IgA 腎病中的方法。在此 - 抱歉，這仍在 PNH 中，對不起。所以 - 這是數據集的概要，我們將很快展示這些數據。您可以再次看到該研究的設計有可能改變 PNH 的實踐。正如我所說，我們期待在即將召開的大會上概述這個主要終點和次要終點。

Moving to Slide 19. Now turning to the IgAN study APPLAUSE for iptacopan, we wanted to clarify that our current filing plan aligned with the FDA, that's a 9-month analysis, to assess superiority in reduction of proteinuria at 9 months. A statistical plan has been agreed. This would support a U.S. Subpart H approval for accelerated approval. We would then continue to follow these patients to look for the more definitive endpoint and to look at flowing progression for IgAN, which would take to the end of the study in 2025, enabling the approval to convert to a full approval. So that's the approach we'll take with IgAN, and we'll look forward to sharing that data towards the end of this year.

轉到幻燈片 19。現在轉向 IgAN 研究 applause for iptacopan，我們想澄清我們目前的申請計劃與 FDA 一致，這是一項為期 9 個月的分析，以評估在 9 個月時減少蛋白尿的優勢。已商定統計計劃。這將支持美國 Subpart H 批准加速批准。然後我們將繼續跟踪這些患者以尋找更明確的終點並觀察 IgAN 的流動進展，這將在 2025 年研究結束，從而使批准轉換為完全批准。這就是我們將對 IgAN 採取的方法，我們期待在今年年底前分享這些數據。

Now moving to Slide 20. I did want to highlight a couple of earlier-stage assets where we're continuing to progress now really with a focus on large potential assets in the pipeline. These include drugs like XXB in cardiovascular disease. This is an NPR1 agonist given infrequently a monoclonal antibody for resistant hypertension and heart failure. YTB, our T-Charge platform, where we presented additional data at ASH, where we are now pursuing this both in the front line large B-cell lymphoma, but importantly, also in multiple immunology indication on the back of data, suggesting that we can take refractory patients into remission, at least in small-scale studies, and that's something we're looking at more carefully.

現在轉到幻燈片 20。我確實想強調一些早期階段的資產，我們現在正在繼續取得進展，重點是管道中的大量潛在資產。其中包括治療心血管疾病的 XXB 等藥物。這是一種 NPR1 激動劑，不經常給予單克隆抗體治療頑固性高血壓和心力衰竭。 YTB，我們的 T-Charge 平台，我們在 ASH 上展示了額外的數據，我們現在正在大 B 細胞淋巴瘤的前線進行研究，但重要的是，也在數據背後的多種免疫學適應症中進行研究，這表明我們至少在小規模研究中，可以使難治性患者病情緩解，這是我們正在更仔細地研究的事情。

Additional radioligand therapies, including in breast cancer and glioblastoma. PPY, which is our gene therapy in ophthalmology for geographic atrophy, which we acquired as part of the Gyroscope acquisition. And lastly, DLX, the partnered compound analysis, oral a-Synuclein inhibitor for Parkinson's disease. All high-risk projects, as is always the case in the stage of development, but all with the potential if they were to work to be very transformational medicines.

其他放射配體療法，包括乳腺癌和膠質母細胞瘤。 PPY，這是我們在眼科治療地圖樣萎縮的基因療法，我們在收購 Gyroscope 時獲得了它。最後，DLX，合作化合物分析，用於帕金森病的口服α-突觸核蛋白抑製劑。所有高風險項目，在開發階段總是如此，但如果它們能夠成為非常具有變革性的藥物，它們都有潛力。

Now moving to Slide 21. Now turning to the growth profile of the company and why we believe we can deliver that 4% growth. We have these 6 in-line brands, these 3 major launch assets, Pluvicto, Scemblix and iptacopan, and these additional pipeline assets that I've outlined. And that's why we continue to believe that we have the firepower in-house with the assets we have to be able to generate that 4% growth, with that 40% margin and create a very attractive profile in the coming years.

現在轉到幻燈片 21。現在轉向公司的增長概況，以及為什麼我們相信我們可以實現 4% 的增長。我們擁有這 6 個在線品牌、這 3 個主要的啟動資產、Pluvicto、Scemblix 和 iptacopan，以及我概述的這些額外的管道資產。這就是為什麼我們繼續相信我們擁有內部火力和資產，我們必須能夠產生 4% 的增長，40% 的利潤率，並在未來幾年創造一個非常有吸引力的形象。

Now moving to Slide 22. The drivers of our growth in this year or this past year were primarily Entresto, Kesimpta and Kisqali, with major contributions from Pluvicto as well as, to a lesser extent, Scemblix and Leqvio. And we expect that those assets to continue to have robust growth over the coming years. Now importantly, we'll discuss a bit more detailed Cosentyx and some of the dynamics there. But the critical element for our Cosentyx story will be life cycle management and the next wave of indications, as well as continued growth in Europe and China, and I'll go through that in a moment.

現在轉到幻燈片 22。我們今年或過去一年的增長驅動力主要是 Entresto、Kesimpta 和 Kisqali，主要貢獻來自 Pluvicto 以及較小程度上的 Scemblix 和 Leqvio。我們預計這些資產在未來幾年將繼續強勁增長。現在重要的是，我們將討論更詳細的 Cosentyx 和那裡的一些動態。但我們 Cosentyx 故事的關鍵要素將是生命週期管理和下一波適應症，以及歐洲和中國的持續增長，我稍後會詳細介紹。

Now moving to Slide 23. When you look at Entresto, continued strong performance, 44% growth quarter-on-quarter. You can see the U.S. weekly TRx continue to climb, demonstrating that Entresto really now is the treatment of choice for patients with preserved -- with heart failure, meeting the guidelines within the label and the relevant cardiovascular guidelines. You see the NBRx is up 16%. We continue to see strong growth in Europe. In China and Japan, we also have contribution from intrusive use and resistant hypertension.

現在轉到幻燈片 23。當你看 Entresto 時，它繼續表現強勁，環比增長 44%。你可以看到美國每週的 TRx 繼續攀升，表明 Entresto 現在確實是保留心力衰竭患者的治療選擇，符合標籤內的指南和相關的心血管指南。你看 NBRx 上漲了 16%。我們繼續看到歐洲的強勁增長。在中國和日本，我們也有侵入性使用和頑固性高血壓的貢獻。

And we remain confident in the ongoing growth profile as we continue to penetrate in heart failure, continue to generate additional real-world data, and we see that launch momentum in Asia as well.

我們對持續的增長前景充滿信心，因為我們繼續深入研究心力衰竭，繼續產生更多的真實世界數據，我們在亞洲也看到了這種啟動勢頭。

Now moving to Slide 24 and turning to Cosentyx. I think as many of you have already seen, Cosentyx Q4 sales were impacted by a revenue deduction true-up related to prior quarters. This was related to a higher level of Medicaid utilization than we had expected. This is a delayed data that we receive from the various Medicaid channel sources. And that led to a higher revenue deduction for the previous quarters, which we took fully in quarter 4.

現在轉到幻燈片 24 並轉向 Cosentyx。我認為正如你們中的許多人已經看到的那樣，Cosentyx 第 4 季度的銷售額受到與前幾個季度相關的收入扣除調整的影響。這與比我們預期的更高水平的醫療補助利用有關。這是我們從各種醫療補助渠道來源收到的延遲數據。這導致前幾個季度的收入扣除額更高，我們在第 4 季度完全扣除了。

When we fully neutralize for that, we saw the U.S. actually declined 6%. And when we look at all of the puts and takes, we see the U.S. largely being in line right now with respect to Cosentyx performance in 2022 versus the prior year. We would expect, in the U.S. for 2023, to continue to see in line growth. So that's -- when we look at all of the dynamics, you will see in the first half of the year some declines in Cosentyx as we lap the fact that in the previous year you had these deductions, which were not factored in.

當我們完全抵消這一點時，我們看到美國實際下跌了 6%。當我們查看所有看跌期權時，我們看到美國目前在 Cosentyx 2022 年與上一年的表現方面基本一致。我們預計，到 2023 年，美國的銷量將繼續保持增長。所以這就是——當我們查看所有動態時，你會在今年上半年看到 Cosentyx 的一些下降，因為我們承認在前一年你有這些扣除的事實，這些扣除沒有被考慮在內。

But underlying, we expect Cosentyx to be able to hold its current performance in the U.S. And then growth that really enables us to get to that mid-single-digit growth will be driven by Europe and China, where we continue to see strong growth -- double-digit growth in China overall. And that will enable us to be well set up for what will come next, which is primarily the life cycle management of this brand.

但從根本上講，我們預計 Cosentyx 能夠保持其目前在美國的表現。然後真正使我們能夠達到中等個位數增長的增長將由歐洲和中國推動，我們將繼續看到強勁的增長 - - 中國整體實現兩位數增長。這將使我們能夠為接下來的事情做好準備，這主要是該品牌的生命週期管理。

And turning to life cycle management. When you go to the next slide, Slide 25, really for Cosentyx now to continue its trajectory to get to the $7 billion, which we remain confident in, it will be around launching these next wave of indications successfully. For Hidradenitis Suppurativa, we expect the approvals in Europe in the first half of this year and in the U.S. in the second half of this year. This is a large indication where only one competitor product is approved, the TMS. So we'll be first to market as a novel agent in this whole setting. And so it's an exciting opportunity to bring this new therapy to this patient population.

並轉向生命週期管理。當你轉到下一張幻燈片時，幻燈片 25，真正讓 Cosentyx 現在繼續其軌跡以達到 70 億美元，我們仍然對此充滿信心，它將圍繞成功啟動這些下一波適應症展開。對於化膿性汗腺炎，我們預計今年上半年在歐洲獲得批准，今年下半年在美國獲得批准。這是一個很大的跡象，只有一種競爭產品獲得批准，即 TMS。因此，我們將率先在整個環境中作為新型代理上市。因此，將這種新療法帶給這一患者群體是一個令人興奮的機會。

We have the intravenous U.S. launch, where we'd be the first novel post-TNF medicine to be available in an intravenous formulation. We expect that launch in the second half of 2023. A new auto-injector. And then the continued work we have on giant cell arteritis and lupus nephritis, again, indications where Cosentyx has generated, I think, compelling data. So taken together, when we look at this profile for life cycle management, the profile we have ex U.S. and the stabilization of the U.S. business, we feel confident we'll get to that $7 billion peak sales potential over time.

我們在美國推出了靜脈注射藥物，我們將成為第一個以靜脈注射製劑形式提供的新型後 TNF 藥物。我們預計該產品將於 2023 年下半年推出。一種新的自動注射器。然後我們在鉅細胞動脈炎和狼瘡性腎炎方面的持續工作，再次表明 Cosentyx 已經產生了令人信服的數據。因此，綜合來看，當我們查看生命週期管理的概況、我們在美國以外的概況以及美國業務的穩定性時，我們有信心隨著時間的推移達到 70 億美元的銷售峰值。

Then moving to Slide 26. You saw that Kesimpta is continuing its strong growth trajectory with 28% constant currency growth, primarily driven by the U.S., though we now start to see a pickup as well outside the United States. Importantly, the key driver for this is the ongoing utilization of Kesimpta in patients who were previously on braces or were naive to any multiple sclerosis therapy. It's important to note that in the B-cell share of the total market is only about 50%. So half the market continues to receive older therapies.

然後轉到幻燈片 26。你看到 Kesimpta 繼續其強勁的增長軌跡，貨幣增長率保持在 28%，這主要是由美國推動的，儘管我們現在開始看到美國以外的地區也有所回升。重要的是，這的關鍵驅動因素是 Kesimpta 在以前戴過牙套或未接受過任何多發性硬化症治療的患者中的持續使用。值得注意的是，B 細胞在整個市場中的份額僅為 50% 左右。因此，一半的市場繼續接受舊療法。

Our Kesimpta exit share was 30%, and we plan to continue to grow that with a goal to get to 50% share of B-cell patients over time. So really good efficacy profile, strong convenience profile. So we'll continue to look forward to launching Kesimpta around the world and driving that dynamic U.S. performance.

我們的 Kesimpta 退出份額為 30%，我們計劃繼續增長，目標是隨著時間的推移達到 50% 的 B 細胞患者份額。所以真的功效性好，方便性強。因此，我們將繼續期待在全球推出 Kesimpta 並推動美國的動態表現。

Now moving to Slide 27. Kisqali had strong growth across all geographies. And when you look at that 33% growth, that's driven by a recognition that Kisqali really is the agent with the best data sets in the metastatic breast cancer setting today. And that's, I think, been really captured by the NCCN guideline update that happened just a few days ago, where Kisqali was named the only Category 1 treatment for first-line metastatic breast cancer patients with a neuromatase inhibitor, which is the majority of patients in the metastatic setting.

現在轉到幻燈片 27。Kisqali 在所有地區都有強勁增長。當你看到 33% 的增長時，這是由於認識到 Kisqali 確實是當今轉移性乳腺癌環境中擁有最佳數據集的藥物。我認為，幾天前發生的 NCCN 指南更新真正抓住了這一點，其中 Kisqali 被命名為使用神經酶抑製劑的一線轉移性乳腺癌患者的唯一 1 類治療，這是大多數患者在轉移環境中。

So with that NCCN guideline update now and as we continue to communicate that to physicians, this hopefully will give us continued momentum, as you can see with Kisqali now getting to 27% in DRx share. And hopefully, we'll see in that metastatic setting, that continued climb on the back of the data sets that we've presented, NCCN guidelines, broad momentum coming out of the San Antonio Breast Cancer Congress as well.

因此，現在隨著 NCCN 指南的更新以及我們繼續與醫生溝通，這有望給我們帶來持續的動力，正如您所看到的，Kisqali 現在在 DRx 份額中達到 27%。希望我們會在轉移環境中看到，在我們提供的數據集、NCCN 指南以及聖安東尼奧乳腺癌大會產生的廣泛勢頭的支持下繼續攀升。

And then that will flow into, of course, the NATALEE readout, which we've already discussed, and the ongoing HARMONIA head-to-head study we have ongoing versus Ibrance. Notably as well, we did achieve an approval in China for Kisqali, which will be another growth driver for this brand going forward.

然後，當然，這將流入我們已經討論過的 NATALEE 讀數，以及我們正在進行的 HARMONIA 與 Ibrance 的頭對頭研究。同樣值得注意的是，我們確實在中國獲得了 Kisqali 的批准，這將成為該品牌未來的另一個增長動力。

Now moving to Slide 28. Zolgensma maintained the leading share in patients with SMA less than 2 years of age. But Q4 growth was muted, and this was really because we've now penetrated a lot of -- most of the bolus and not the entire bolus, the prevalent patients in most of our key geographies. And growth now is largely dependent on adding additional countries in emerging markets around the world. And so we expect with this brand to stabilize in the $1.5 billion range until we get the readout and hopeful approval in the intrathecal setting.

現在轉到幻燈片 28。Zolgensma 在 2 歲以下的 SMA 患者中保持領先地位。但是第四季度的增長是緩慢的，這真的是因為我們現在已經滲透了很多 - 大部分推注而不是整個推注，我們大多數關鍵地區的流行患者。現在的增長在很大程度上取決於在全球新興市場中增加更多國家。因此，我們預計這個品牌將穩定在 15 億美元的範圍內，直到我們在鞘內環境中獲得讀數和有希望的批准。

We'll continue to work to increase newborn screening. Importantly, in Europe, that's at 45%, and we have the opportunity, we believe, to drive that up further, it could be a source of growth as well as adding on additional markets in Latin America, the Middle East and other parts of the world. But the key next inflection point for Zolgensma will certainly be the readout of the STEER study of intrathecal patients and the STRENGTH study in the use of IV Zolgensma patients in 2 to 5 years of age. Those studies are enrolling on track, and then we'll hopefully have data sets to share in the coming years.

我們將繼續努力增加新生兒篩查。重要的是，在歐洲，這一比例為 45%，我們相信，我們有機會進一步提高這一比例，這可能成為增長的源泉，並增加拉丁美洲、中東和美國其他地區的額外市場世界。但 Zolgensma 的下一個關鍵轉折點肯定是鞘內註射患者的 STEER 研究和 2 至 5 歲患者使用 IV Zolgensma 患者的 STRENGTH 研究的讀數。這些研究正在按計劃進行，然後我們有望在未來幾年內分享數據集。

Moving to Slide 29. I wanted to turn to Leqvio and give you an update on where we are now as we continue to build a strong foundation for this brand to become a significant cardiovascular medicine for the company. With respect to access, we're now at 76% of patients covered at or near label. In terms of adherence, we're seeing 75% of patients today coming in for their second dose. We now have 1,700 centers that have ordered Leqvio. And we've been able to increase between Q3 and Q4 about 50%, the number of HCPs who prescribed Leqvio either through a paid dose or through our free trial offer to now 7,200 physicians.

轉到幻燈片 29。我想轉向 Leqvio 並向您介紹我們現在的最新情況，因為我們繼續為這個品牌打下堅實的基礎，使其成為公司重要的心血管藥物。關於訪問，我們現在有 76% 的患者在標籤上或附近覆蓋。在依從性方面，我們看到今天有 75% 的患者接受了第二次給藥。我們現在有 1,700 個中心訂購了 Leqvio。我們已經能夠在第三季度和第四季度之間增加約 50%，通過付費劑量或通過我們現在的 7,200 名醫生的免費試用提供 Leqvio 處方的 HCP 數量。

So we continue to build that strong base, continue to generate important data. The ORION-3 data was recently published. Our Phase III secondary prevention studies are enrolling well. We've launched now our primary prevention studies, which we'll expect to start in the first half of 2023 and continue to build out a robust data set for this medicine.

因此，我們繼續建立強大的基礎，繼續生成重要數據。 ORION-3 數據最近公佈。我們的 III 期二級預防研究招募情況良好。我們現在已經啟動了初級預防研究，預計將於 2023 年上半年開始，並繼續為該藥物建立強大的數據集。

Now moving to Slide 30. When you look at where Entresto is and compare it to where -- sorry, where Leqvio is and compared to where Entresto was in the U.S., we're largely in line with what we saw in the Entresto launch. A slow ramp as we build up awareness amongst physicians, get all of the various elements in place and really build momentum in the cardiovascular community for use of a new medicine or, in this case, a new approach to controlling cholesterol. So we're on track versus the Entresto ramp, and that's the ramp we would expect to see over the course of the coming months with respect to Leqvio with a goal, of course, to accelerate wherever we can.

現在轉到幻燈片 30。當你查看 Entresto 的位置並將其與哪裡進行比較時——抱歉，Leqvio 的位置以及與 Entresto 在美國的位置相比，我們在很大程度上與我們在 Entresto 發佈時看到的一致。隨著我們在醫生中建立起意識，獲得所有各種要素並真正在心血管社區建立使用新藥或在這種情況下控制膽固醇的新方法的勢頭，緩慢上升。因此，與 Entresto 相比，我們正在走上正軌，這就是我們預計在未來幾個月內看到的關於 Leqvio 的斜坡，當然，我們的目標是盡可能加速。

When you look at the U.S., the key accelerators are going to be new facilities getting more depth in our existing prescribers, and continuing to educate HCPs is on the Part B reimbursement process. We also would expect, over the course of this year, to get additional conversion from the free trial offer that we rolled out in the second half of last year.

當你看看美國時，關鍵的加速器將是新設施，讓我們現有的處方者更深入，繼續教育 HCPs 是關於 B 部分報銷流程。我們還預計，在今年，我們將從去年下半年推出的免費試用優惠中獲得更多轉化。

Outside the United States, a big focus at the NHS is to get a broader prescriber breadth in the U.K. And then we'll have the hopeful approval in the back half of this year in China, which will allow us to have a major geography where we can further accelerate global Leqvio performance.

在美國以外，NHS 的一個重點是在英國擴大處方範圍。然後我們將在今年下半年在中國獲得有希望的批准，這將使我們擁有一個主要的地理區域我們可以進一步加速 Leqvio 的全球性能。

Moving to Slide 31. Pluvicto, I think, as you've all seen, is off to an outstanding start in the United States. And this is reflective of very strong demand we're seeing for this medicine. $179 million in quarter 4, full year sales of $270 million, almost entire -- all of that was in the U.S. We are seeing NBRx share at 18%, and that continues to climb in the post-taxane mCRPC setting, 160 unique accounts. We have very good payer coverage, permanent A code is now in effect. We're approved in Europe.

轉到幻燈片 31。正如你們所見，我認為 Pluvicto 在美國取得了出色的開端。這反映出我們對這種藥物的需求非常強勁。第 4 季度 1.79 億美元，全年銷售額 2.7 億美元，幾乎全部——所有這些都在美國。我們看到 NBRx 的份額為 18%，並且在紫杉烷後 mCRPC 設置中繼續攀升，160 個獨特的賬戶。我們有很好的付款人覆蓋範圍，永久 A 代碼現已生效。我們在歐洲獲得批准。

So this is a story now where we continue to see very strong demand in the U.S., and we see strong demand in Europe, and we're scaling our manufacturing capacity to meet that demand.

所以現在這是一個故事，我們繼續看到美國的強勁需求，我們看到歐洲的強勁需求，我們正在擴大我們的製造能力以滿足這種需求。

And when you look at the next slide, our Pluvicto manufacturing capacity is going to expand over the course of 2023. Our expectations are we'll be able to move across 4 facilities that will have online for this medicine versus a single facility right now that's the primary source areas today. We're working hard to bring Millburn online by the middle of this year, which will allow us for another capacity expansion.

當您查看下一張幻燈片時，我們的 Pluvicto 製造能力將在 2023 年期間擴大。我們的期望是，我們將能夠跨越 4 個在線生產這種藥物的設施，而不是現在只有一個設施今天的主要來源地區。我們正努力在今年年中之前讓 Millburn 上線，這將使我們能夠進行另一次產能擴張。

Then later this year an automated, brand-new facility in Indianapolis with substantial capacity. And then for the rest of the world, Zaragoza facility in Spain, which would then further expand our capacity for Europe. We're also evaluating adding additional manufacturing sites in Asia at this time. With the 4 facilities you have here, we're targeting capacity of over 250,000 doses annually in 2024 and beyond. And then we'll continue to expand that capacity by adding additional facilities if the demand warrants it.

然後在今年晚些時候在印第安納波利斯建立了一個自動化的全新設施，容量很大。然後對於世界其他地區，西班牙的薩拉戈薩工廠將進一步擴大我們在歐洲的產能。我們也在評估此時在亞洲增加額外的製造基地。有了你們這裡的 4 個設施，我們的目標是在 2024 年及以後每年生產超過 250,000 劑疫苗。然後，如果需求允許，我們會通過增加額外的設施來繼續擴大產能。

Now moving to Slide 33. Scemblix is off also to a strong start. You can see the sales here $150 million on the full year, NBRx share at 29%. And probably the most important element here of this story will be the ASH preferred study, which we're enrolling ahead of plan. We expect to read out in 2024, which will enable us to potentially move this medicine in the first-line setting and potentially be used as an alternative to imatinib or some of the other first and second-generation TKIs.

現在轉到幻燈片 33。Scemblix 也有一個良好的開端。你可以在這裡看到全年銷售額為 1.5 億美元，NBRx 的份額為 29%。這個故事中最重要的元素可能是 ASH 首選研究，我們正在提前註冊。我們預計在 2024 年宣讀，這將使我們有可能將這種藥物用於一線治療，並有可能用作伊馬替尼或其他一些第一代和第二代 TKI 的替代品。

Now moving to Slide 34. I'll hand it over to Harry now for the financial review. Harry?

現在轉到幻燈片 34。我現在將它交給 Harry 進行財務審查。哈利？

Yes. Thank you, Vas. Good morning, good afternoon, everyone. I'm now going to talk you through some of the financials for 2022 as well as provide you with our 2023 guidance. As always, my comments refer to growth rates in constant currencies unless otherwise noted. So next slide, please.

是的。謝謝你，瓦斯。大家早上好，下午好。我現在將向您介紹 2022 年的一些財務狀況，並為您提供我們的 2023 年指導。與往常一樣，除非另有說明，否則我的評論指的是固定匯率的增長率。請切換到下一張幻燈片。

I would like to begin by comparing our performance with the latest guidance we provided in October last year. As you can see, we generally met our guidance across the divisions and at group level, with a notable beat for group core operating income, which was largely driven by Innovative Medicines performance. As you can see, Sandoz top line also returned to growth, with core operating income impacted by higher-than-expected inflationary pressures on input costs. Next slide, please.

首先，我想將我們的表現與去年 10 月提供的最新指導進行比較。正如您所看到的，我們在各個部門和集團層面總體上達到了我們的指導，集團核心營業收入顯著增長，這在很大程度上是由創新藥物的業績推動的。如您所見，Sandoz 的收入也恢復增長，其核心營業收入受到高於預期的投入成本通脹壓力的影響。請換下一張幻燈片。

Taking a step back for a moment, you see that our 2022 performance was a continuation of our strong track record for Innovative Medicines. Over the last 3 years, we have delivered a 5% CAGR growth in sales and double of that at 10% CAGR on core operating income. Obviously, this performance has resulted in margin improving from approximately 33% beginning of this time period to now 37%, an increase of 480 basis points in constant currencies over 3 years. In short, we are delivering consistent performance against our financial targets and intend to continue to deliver improved financials, of course.

退後一步，您會發現我們 2022 年的表現延續了我們在創新藥物方面的良好記錄。在過去 3 年中，我們的銷售額實現了 5% 的複合年增長率，核心營業收入以 10% 的複合年增長率翻了一番。顯然，這種表現導致利潤率從這段時間開始時的約 33% 提高到現在的 37%，按固定匯率計算，在 3 年內增長了 480 個基點。簡而言之，我們正在根據我們的財務目標提供一致的業績，當然，我們打算繼續提供更好的財務狀況。

Turning to Slide 37. I will focus on the full year numbers on the right-hand side. For the full year, as Vas has already laid out, sales grew 4% and core operating income 8%. Operating income was down 13% mainly due to the higher restructuring costs related to the implementation of our streamlined organizational model. Net income was $7 billion, with the comparison versus '21 million impacted by the Roche stake divestment income. Recall, we had a onetime gain of $14 billion when we sold the Roche stake in (inaudible) for $21 billion.

轉到幻燈片 37。我將重點關注右側的全年數字。對於全年，正如 Vas 已經規劃的那樣，銷售額增長了 4%，核心營業收入增長了 8%。營業收入下降了 13%，這主要是由於與實施精簡組織模型相關的重組成本較高。淨收入為 70 億美元，而受羅氏股權剝離收入影響的淨收入為 2100 萬美元。回想一下，當我們以 210 億美元的價格出售羅氏（聽不清）的股份時，我們獲得了 140 億美元的一次性收益。

Core EPS was $6.12, growing 14%, excluding the prior year Roche impact. Free cash flow was $12 billion for the full year, of course, also impacted by the currency movements, but overall a solid free cash flow performance.

核心每股收益為 6.12 美元，增長 14%，不包括上一年羅氏的影響。全年自由現金流為 120 億美元，當然，也受到貨幣變動的影響，但總體而言，自由現金流表現穩健。

Speaking of free cash flow, let's talk about the next slide. Of course, one of my favorite year-end slides. Given our solid 22% free cash flow, we are pleased to propose the 26th consecutive dividend increase to CHF 3.20 per share. This is up 3.2% versus the CHF 3.10 last year, a dividend yield of 3.8%. Of course, this increase is fully in line with our policy of increasing our dividend per share every year in Swiss francs.

說到自由現金流，讓我們談談下一張幻燈片。當然，這是我最喜歡的年終幻燈片之一。鑑於我們穩固的 22% 自由現金流，我們很高興提議連續第 26 次將股息提高至每股 3.20 瑞士法郎。這比去年的 3.10 瑞士法郎上漲了 3.2%，股息收益率為 3.8%。當然，這一增長完全符合我們每年增加以瑞士法郎計算的每股股息的政策。

Now to Slide 39, please? Thank you. Now let's get into some further details about our 2022 margin performance by division. Overall, for the full year, core margin for the group increased 130 basis points to 33% of sales, driven by IM margin, which also increased by 130 basis points to 36.9%. And we'll talk about Sandoz in detail on the next slide.

現在轉到幻燈片 39，好嗎？謝謝。現在讓我們按部門詳細了解我們 2022 年的利潤率表現。總體而言，在 IM 利潤率的推動下，集團全年核心利潤率增長 130 個基點至銷售額的 33%，後者也增長 130 個基點至 36.9%。我們將在下一張幻燈片中詳細討論 Sandoz。

So here is the summary of the Sandoz 2022 performance. It was a good year for the division returning to top line, with sales up 4%, driven by the biopharma growth of 9% and retail growing 4%. Core operating income was essentially flat for the full year, disproportionately affected by inflationary pressures on input costs. As we look in the future, we expect continued share gains across geographies and 2 potential biosimilar U.S. approvals in the second half of 2023. With respect to the planned spin-off, we remain on track to complete this in the second half of the year, pending the required approvals. Next page, please.

所以這裡是 Sandoz 2022 性能的總結。今年是該部門重回頂線的好年景，在生物製藥增長 9% 和零售增長 4% 的推動下，銷售額增長 4%。全年核心營業收入基本持平，主要受到投入成本通脹壓力的影響。展望未來，我們預計 2023 年下半年各地區的份額將持續增長，並且 2 種潛在的生物仿製藥將獲得美國批准。關於計劃中的分拆，我們仍有望在今年下半年完成這項工作，等待所需的批准。請翻下一頁。

As we anticipate a spin-off of Sandoz in the second half of the year, we thought it would be useful to give guidance for Innovative Medicines, Novartis excluding Sandoz and Novartis including Sandoz, to allow for the respective modeling that no doubt you will do. So for Innovative Medicines, we expect sales to grow low to mid-single digits, and core operating income to grow mid- to high single digits.

由於我們預計 Sandoz 將在今年下半年分拆，我們認為為 Innovative Medicines，Novartis excluding Sandoz 和 Novartis including Sandoz 提供指導將很有用，以允許您毫無疑問會做的相應建模.因此，對於創新藥物，我們預計銷售額將增長中低個位數，核心營業收入將增長中高個位數。

Novartis, excluding Sandoz, has, of course, exactly the same growth guidance as Innovative Medicines because the only difference between the two are corporate costs. Now Novartis, including Sandoz, which is essentially today's group, the group guidance is assuming here that Sandoz would remain with the group for the entire year, we would expect sales to grow low to mid-single digit and core operating to grow mid-single digit.

諾華（不包括 Sandoz）當然與 Innovative Medicines 有著完全相同的增長指導，因為兩者之間的唯一區別是公司成本。現在諾華，包括山德士，基本上就是今天的集團，集團的指導假設山德士將全年留在集團，我們預計銷售額將增長到中個位數，核心業務將增長到中個位數數字。

On the next slide, I detail a bit more the Sandoz guidance. So for 2023, we expect the top line for Sandoz to grow low to mid-single digit and the core operating income to decline low double digit. Now this core profit decline reflects the required standup investments and transition costs to separate Sandoz and some continued inflationary pressures. Clearly, with this setting, 2023 would be the trough year for Sandoz core margin given the expected added cost to stand up a public company.

在下一張幻燈片中，我將詳細介紹 Sandoz 指南。因此，到 2023 年，我們預計 Sandoz 的收入將增長到中低個位數，核心營業收入將下降低兩位數。現在，這種核心利潤下降反映了分離 Sandoz 所需的固定投資和轉型成本以及一些持續的通脹壓力。顯然，在這種情況下，2023 年將是 Sandoz 核心利潤率的低谷年，因為成立一家上市公司預計會增加成本。

Looking ahead, with respect to Sandoz midterm potential, sales are expected to grow low to mid-single-digit CAGR and the core margin is expected to expand to the mid-20s driven by continued sales growth and operational efficiencies, especially as a standalone lean generic company.

展望未來，就 Sandoz 的中期潛力而言，預計銷售額將以低至中個位數的複合年增長率增長，核心利潤率預計將擴大至 20 年代中期，這主要得益於持續的銷售增長和運營效率，尤其是作為獨立的精益生產通用公司。

On Slide 43, I would like to add some perspectives on the other key financial elements of our expected core net income performance. In short, we expect both core net financial result and core tax rate to be broadly in line with 2022.

在幻燈片 43 上，我想補充一些關於我們預期核心淨收入表現的其他關鍵財務要素的觀點。簡而言之，我們預計核心淨財務業績和核心稅率都將與 2022 年基本持平。

On the next slide, I would like to go into a little more detail about the tailwinds and headwinds facing core operating income growth in 2023. So the expected drivers of future core operating income growth include, of course, continued performance of our end market growth drivers and the acceleration of recent launches, such as Pluvicto and Leqvio. We also expect China growth to accelerate, benefiting from a return to normal in the second half of the year.

在下一張幻燈片中，我想更詳細地介紹一下 2023 年核心營業收入增長面臨的順風和逆風。因此，未來核心營業收入增長的預期驅動力當然包括我們終端市場增長的持續表現驅動程序和最近發布的加速，例如 Pluvicto 和 Leqvio。我們還預計中國經濟增長將加速，受益於下半年恢復正常。

Additionally, our simplified organizational structure is expected to continue delivering SG&A savings. And of course, we will continue our ongoing productivity programs. Growth will be partly offset by inflationary headwinds, which are expected to continue in 2023. On inflation, some further details as we saw it in -- finalizing in 2022. In 2022, the inflation impact you saw was a bit higher than expected in quarter 4. So for the total company, we estimate that the 2022 inflationary impact was approximately $350 million. However, this was, of course, more than offset by cost control and productivity savings.

此外，我們簡化的組織結構有望繼續節省 SG&A。當然，我們將繼續我們正在進行的生產力計劃。增長將部分被通貨膨脹的逆風所抵消，預計通貨膨脹的逆風將在 2023 年繼續存在。關於通貨膨脹，我們在 2022 年完成了一些進一步的細節。在 2022 年，您看到的通貨膨脹影響略高於本季度的預期4. 因此，對於整個公司，我們估計 2022 年的通貨膨脹影響約為 3.5 億美元。然而，這當然被成本控制和生產力節省所抵消。

In 2023, we expect the inflation impact to be slightly higher, also including some above-normal merit increases at approximately $0.5 billion. This has been fully considered in our 2023 bottom line guidance. The other headwinds are generic erosion of Gilenya in U.S. and potentially to Sandoz in the EU, and the standup investments, as discussed, related to the likely Sandoz spin-off. Despite the headwinds, we continue to anticipate further margin expansion in 2023 and beyond due to the expected sales growth and productivity progress.

到 2023 年，我們預計通貨膨脹的影響會略高，其中還包括一些高於正常水平的績效增長，約為 5 億美元。這已在我們的 2023 年底線指南中得到充分考慮。其他不利因素是美國對 Gilenya 的普遍侵蝕，並可能對歐盟的 Sandoz 造成影響，以及所討論的與可能的 Sandoz 分拆相關的單口投資。儘管存在不利因素，但由於預期的銷售增長和生產力進步，我們繼續預計 2023 年及以後的利潤率將進一步擴大。

Finally, on Slide 45. We thought it would be helpful to go into some detail regarding the currency impacts expected, especially given the significant fluctuations of the last months. As you saw in quarter 4, currency had a negative 7% point impact on net sales and a negative 9% impact on core operating. If late January rates prevail for the remainder of 2023, we expect the full year impact in 2023 of currencies to be much lower. On the top line, it would be 0 to positive 1%, and on the bottom line, slightly negative with minus 1%. As a reminder, we update this given the volatility monthly on our website.

最後，在幻燈片 45 上。我們認為詳細介紹預期的貨幣影響會有所幫助，尤其是考慮到過去幾個月的大幅波動。正如您在第 4 季度看到的那樣，貨幣對淨銷售額產生了 7% 的負面影響，對核心運營產生了 9% 的負面影響。如果 1 月底的利率在 2023 年的剩餘時間裡占主導地位，我們預計 2023 年貨幣的全年影響將低得多。在最上面一行，它將是 0 到正 1%，在最下面一行，略微為負，為負 1%。提醒一下，鑑於我們網站上每月的波動，我們會對此進行更新。

And with that, I hand back to Vas.

就這樣，我交還給 Vas。

Great. Thanks, Harry. Moving to Slide 47. I just wanted to make a note that we continue to focus on our goal to be one of the leaders in impact and sustainability and our approach to ESG as well as just delivering on our core purpose. 290 million patients reached with our Innovative Medicines and our global health portfolio, 453 million patients reached with Sandoz, a broad pipeline across various technology areas, numerous new drug approvals and multiple recent innovation highlights.

偉大的。謝謝，哈利。轉到幻燈片 47。我只想指出，我們將繼續專注於我們的目標，成為影響力和可持續性方面的領導者之一，我們的 ESG 方法以及實現我們的核心目標。 2.9 億患者接觸了我們的創新藥物和我們的全球健康產品組合，4.53 億患者接觸了 Sandoz，這是一個跨越各個技術領域的廣泛管道，眾多新藥批准和多個近期創新亮點。

Just to highlight that we think the greatest contribution we make to the world is based on our ability to discover, develop and ultimately scale and launch new medicines to people across the planet.

只是為了強調，我們認為我們對世界做出的最大貢獻是基於我們發現、開發並最終擴大規模並向全球人民推出新藥的能力。

Then moving to Slide 48. In closing, 8 priorities that will really determine our path going forward. We're transforming the company to a pure-play IM company, 5 core TAs, 5 core technology platforms and our core geographic focus is a focus on the U.S., 9 multibillion-dollar potential brands, a real emphasis on improving our R&D productivity towards high-impact assets and high-value assets, a focus on key TGAs and building depth in those TAs, improving our financials, as you've seen with the margin delivery and the ongoing efforts we have to continue to improve the overall financial picture, shareholder-focused capital allocation as we've shown with our dividend increase share buybacks and continued approach to how we dispose or move forward with assets such as Sandoz to our shareholders and continuing to strengthen our foundations with ESG and human capital.

然後轉到幻燈片 48。最後，8 個優先事項將真正決定我們前進的道路。我們正在將公司轉型為一家純粹的 IM 公司，5 個核心 TA，5 個核心技術平台，我們的核心地理重點是美國，9 個價值數十億美元的潛在品牌，真正強調提高我們的研發生產力，以實現高影響力資產和高價值資產，專注於關鍵的 TGA 並在這些 TA 中建立深度，改善我們的財務狀況，正如您在保證金交付和我們必須繼續改善整體財務狀況的持續努力中看到的那樣，以股東為中心的資本分配，正如我們通過股息增加股票回購以及我們如何向股東處置或推進 Sandoz 等資產以及繼續加強 ESG 和人力資本基礎的方式所表明的那樣。

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

因此，我們可以打開問題熱線。 （操作員說明）

(Operator Instructions)

（操作員說明）

And the first question comes from the line of Matthew Weston from Credit Suisse.

第一個問題來自瑞士信貸的 Matthew Weston。

I'm going to go with a big picture question to start with, because I'm sure others will dig into the detail, it's on drug pricing. The incoming chair for pharma in 2023, I'd love your perspectives on whether the industry sees any success in normalizing the 9 versus 13 exclusivity to small molecules versus biologics. And also your thoughts on EU pricing pressures. There seem to be a lot of pressures building in a number of your core markets, in Germany and France and others, and also some worrying legislation in front of the European Commission. I'd very much love your thoughts given the vast exposure there.

我將從一個大問題開始，因為我相信其他人會深入研究細節，這是關於藥品定價的。作為 2023 年即將上任的製藥業主席，我很想听聽您對業界是否成功將小分子與生物製劑的 9 對 13 排他性歸一化的看法。還有你對歐盟定價壓力的看法。在德國、法國和其他國家的一些核心市場似乎存在著很大的壓力，而且歐盟委員會面前還有一些令人擔憂的立法。鑑於那裡的廣泛曝光，我非常喜歡你的想法。

Thanks, Matthew. So first, our guidance already factors in the various headwinds we see in pricing around the world. So that 4%, 40% and then also the guidance in 2023 already factors this in. So that's an important, I think, caveat. Now to your first question on -- in the U.S., there's 3 core priorities that we have as an industry to take forward now. One is to correct the distortion of the 9 versus 13 small molecule, or NDA versus BLA. Second is a focus on PBM reform. And the third is continuing to improve the 340B program so that it can actually deliver on its intended purpose for patients in low-income settings and who benefit from various programs from federally qualified health care clinics.

謝謝，馬修。因此，首先，我們的指導已經考慮到我們在全球定價中看到的各種不利因素。所以 4%、40% 以及 2023 年的指導已經考慮到了這一點。所以我認為這是一個重要的警告。現在回答你的第一個問題——在美國，作為一個行業，我們現在有 3 個核心優先事項需要推進。一種是糾正 9 對 13 小分子或 NDA 對 BLA 的扭曲。二是注重PBM改革。第三是繼續改進 340B 計劃，以便它能夠真正為低收入環境中的患者實現預期目的，並使他們受益於聯邦合格醫療診所的各種計劃。

Now on your specific question on the 9 versus 13, I think we have very good arguments as to why this creates an unintended long-term innovation distortion, which disadvantages small molecule and related medicines for the Medicare population, indication expansions in cancer, medicines that take longer to ramp in cardiovascular disease or in respiratory disease. So all things that need to be considered. I think the key thing will be when, in the coming years, there's a legislative vehicle for us to be able to pursue that. But it's a top priority of the industry.

現在關於你關於 9 和 13 的具體問題，我認為我們有很好的論據來說明為什麼這會造成意想不到的長期創新扭曲，這不利於醫療保險人群的小分子和相關藥物、癌症的適應症擴展、藥物需要更長的時間才能引發心血管疾病或呼吸系統疾病。因此，所有需要考慮的事情。我認為關鍵在於，在未來幾年，我們將有一個立法工具來實現這一目標。但這是行業的重中之重。

And I think, at least my belief is our industry when we come together to really focus on a topic and have a very clear compelling policy case and a relatively small pay for from a congressional standpoint, that we can make it happen, and that's going to be our total focus as a sector in the U.S. Now on the EU pricing pressures, it's a little bit of a mixed bag. Certainly, we are concerned by some of the actions in the U.K., actions -- proposed actions in France. Germany has had some headwinds. But overall, the German environment, we'd say is relatively positive and workable.

而且我認為，至少我相信我們的行業，當我們聚在一起真正專注於一個主題並且有一個非常明確的令人信服的政策案例並且從國會的角度來看支付的費用相對較少時，我們可以實現它，而且這將會發生成為我們作為美國一個部門的全部焦點。現在歐盟的定價壓力，它有點複雜。當然，我們對英國的一些行動、法國的行動——提議的行動感到擔憂。德國遇到了一些不利因素。但總的來說，我們認為德國的環境是相對積極和可行的。

But I'd say, broadly speaking, I think we as a sector need to do a better job clarifying the policymakers that in order to invest in innovation in Europe, we need a pricing environment that rewards innovation, particularly when it improves the outcomes for patients. And this can be seen as a place to constantly cut costs, especially relative to the rest of the world. So that's going to be our focus to try to educate. But for us, I think Germany remains the most attractive market. And therefore, I think from a financial outlook standpoint, we feel comfortable with the guidance that we've given. Thank you, Matthew. Next question, operator?

但我想說，從廣義上講，我認為我們作為一個行業需要做得更好，向政策制定者澄清，為了在歐洲投資創新，我們需要一個獎勵創新的定價環境，特別是當它改善了結果時患者。這可以看作是不斷削減成本的地方，尤其是相對於世界其他地區而言。所以這將是我們嘗試教育的重點。但對我們來說，我認為德國仍然是最具吸引力的市場。因此，我認為從財務前景的角度來看，我們對我們給出的指導感到滿意。謝謝你，馬修。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。

So it's on Pluvicto. So it's now annualizing in over $700 million, which I think was pretty close to your peak guide for the vision-labeled indication. So is that a steady state number? Or can you see growth expanding from this quarter-on-quarter? So have you hit your supply capacity constraints now until you get more supply coming online? And could you just underestimate the vision population here, given it's penetrated so quickly?

所以它在 Pluvicto 上。因此，它現在的年化收入超過 7 億美元，我認為這非常接近視覺標記適應症的峰值指南。那麼這是一個穩態數字嗎？或者你能看到這個季度環比增長嗎？那麼，在獲得更多供應之前，您現在是否已經達到了供應能力限制？你能不能低估這裡的視力人群，因為它滲透得如此之快？

And then on your capacity into next year, you said that the number of doses around 250,000. Correct me if I'm wrong, that would equate to around 50,000 patients, which is over $8 billion of revenue potential at U.S. prices. So perhaps just give us a feel for what you think the top peak numbers for this drug could be in the context of the 2 billion that you've been putting into the slides for PSMAfore and PSMAddition.

然後關於您明年的產能，您說的劑量約為 250,000 劑。如果我錯了，請糾正我，這相當於大約 50,000 名患者，按美國價格計算，這意味著超過 80 億美元的收入潛力。因此，也許只是讓我們了解一下您認為這種藥物的最高峰值數字可能是在您一直在 PSMAfore 和 PSMAddition 幻燈片中放入的 20 億的背景下。

So first, I think from a demand standpoint, I would say our initial estimate of the vision population have underestimated the potential of this population and the demand would suggest to us that there are a greater number of patients and providers interested in this medicine. So we certainly have not fully penetrated the vision population in the United States. And really, it's a question of us continuing to expand our capacity to meet what is the much larger interested population than we initially expected. And so we're working towards that.

因此，首先，我認為從需求的角度來看，我想說我們對視力人群的初步估計低估了這一人群的潛力，需求會向我們表明有更多的患者和提供者對這種藥物感興趣。所以我們當然還沒有完全滲透到美國的視覺人群中。實際上，這是一個問題，我們需要繼續擴大我們的能力，以滿足比我們最初預期更多的感興趣的人群。所以我們正在為此努力。

As I mentioned, we're working with multiple sites to have online over the course of this year. Ideally, and if according to plan by the middle of this year, but that's dependent on regulatory action and then additional sites towards the end of this year as well. So we would expect if we can meet the demand that there will be continued growth from the vision population in and of itself. Now I think beyond that, with the PSMAfore, PSMAddition, we certainly see this medicine becoming a very significant medicine for the company, assuming the data reads out positively over the coming readouts.

正如我所提到的，我們正在與多個網站合作，以便在今年內上線。理想情況下，如果按照今年年中的計劃，但這取決於監管行動，然後是今年年底的額外站點。因此，我們預計，如果我們能夠滿足需求，視力人口本身就會持續增長。現在我認為除此之外，有了 PSMAfore，PSMAddition，我們肯定會看到這種藥物成為公司非常重要的藥物，假設數據在即將到來的讀數中讀出積極的結果。

That will take, of course, the readouts have to come through, but we're preparing from a capacity standpoint to have this be a very large medicine for Novartis. And you see that -- I also mentioned we're preparing as well as to add additional facilities in Asia. We have advanced already planning on those 2 additional facilities. So we'll be ready to make this medicine around the world available to many prostate cancer patients as we can.

當然，這需要通過讀數，但我們正從容量的角度準備讓這成為諾華公司的一種非常大的藥物。你看到了——我還提到我們正在準備並在亞洲增加額外的設施。我們已經提前計劃了這兩個額外的設施。因此，我們已做好準備，盡可能讓世界各地的許多前列腺癌患者都能使用這種藥物。

And so just to be clear, have you reached capacity already? Or is there further capacity that you can still fill with increased demand?

所以要明確一點，你已經達到容量了嗎？或者是否還有更多產能可以滿足需求的增長？

We have further capacity versus Q4, but we certainly need to continue to work -- to further expand the capacity given the size of the opportunity, the size of the demand that we're seeing. We have some limited additional capacity versus Q4, but we need to expand further to fully meet the demand for sure. So I think from how you model this, I think in the first half of this year, it should be modest growth as we work to expand the facilities. And then assuming we get the facilities online, we would hope a ramp up then in the second half as those -- that additional capacity comes online. And then moving into next year, of course, we have the additional capacity, additional geographies and then, hopefully as well, the PSMAddition population as well.

與第四季度相比，我們有更多的產能，但我們當然需要繼續努力——鑑於機會的規模和我們所看到的需求規模，進一步擴大產能。與第四季度相比，我們的額外產能有限，但我們需要進一步擴張才能完全滿足需求。所以我認為從你如何建模來看，我認為在今年上半年，隨著我們努力擴大設施，它應該是溫和的增長。然後假設我們讓設施上線，我們希望在下半年增加這些設施——額外的容量上線。然後進入明年，當然，我們有更多的容量，更多的地理位置，然後，希望還有 PSMAddition 人口。

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。

We noted that the Phase II data for your obesity agent, MBL949, is due in May. I don't believe Novartis has stated the mechanism other than it's not an incretin. Can you confirm that it targets Anti-ACTR3? And is it the same as or similar to the molecule you previously out-licensed? And I'm also curious on the same topic, why you didn't highlight it on Slide 20? Are you not excited about this target? Or are you not excited about obesity?

我們注意到你們的肥胖藥物 MBL949 的 II 期數據將於 5 月到期。我不相信 Novartis 已經說明了除了它不是腸促胰島素之外的機制。你能確認它針對的是Anti-ACTR3嗎？它與您之前授權的分子相同或相似嗎？我也對同一主題很好奇，為什麼您沒有在 Slide 20 上突出顯示它？你對這個目標不感興趣嗎？還是您對肥胖不感興趣？

Yes. I can say definitively, it's not related to BYL, the molecule that we out-licensed. We are not disclosing the mechanism of action. You are correct that we do expect the readout in quarter 2. And the simple reason we didn't highlight on the slide is we view it as a high-risk, high-reward program. Now they're all high risk, high reward, but I think particularly for agents of obesity, the key is can we find a dose and schedule that leads to both profound weight loss and a tolerability profile. And I don't know -- I've not seen the data, so I don't know. But I mean, that's the key question, and that's why we didn't -- chose not to put it on the slide until we have further data, which we'll have in the second quarter. And then, of course, we'll provide an appropriate update at that time.

是的。我可以肯定地說，它與 BYL 無關，BYL 是我們授權的分子。我們沒有透露作用機制。您是正確的，我們確實希望在第二季度進行讀數。我們沒有在幻燈片上突出顯示的簡單原因是我們將其視為高風險、高回報的計劃。現在它們都是高風險、高回報，但我認為特別是對於肥胖症患者而言，關鍵是我們能否找到既能顯著減輕體重又能耐受的劑量和時間表。我不知道——我沒有看到數據，所以我不知道。但我的意思是，這是關鍵問題，這就是為什麼我們沒有——選擇不把它放在幻燈片上，直到我們有更多的數據，我們將在第二季度獲得。然後，當然，我們會在那個時候提供適當的更新。

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

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

On Cosentyx, what's driving the higher Medicaid channel mix? And could that somehow increase further? Or might it actually reverse out as Medicaid enrollment numbers potentially shrink with the U.S. declaring that the pandemic is over? And then an update on formulary positioning in '23 in terms of lives covered and a preferred spot. And also, if you can comment on whether there's any new access restrictions and what the rebating was like in '23 relative to prior periods?

在 Cosentyx 上，是什麼推動了更高的醫療補助渠道組合？這會以某種方式進一步增加嗎？還是隨著美國宣布大流行病結束，醫療補助註冊人數可能會減少，它實際上可能會逆轉嗎？然後根據覆蓋的生命和首選位置更新 23 年的處方定位。而且，您是否可以評論是否有任何新的訪問限制以及 23 年相對於之前期間的回扣情況如何？

Yes. Thanks, Tim. All great questions. So first, on the Medicaid increase. First, it's important to note with a brand like this, $3 billion of net sales, significantly more gross sales, the actual percentage variation here is not huge. Nonetheless, we don't have a great handle on why exactly the Medicaid came up a bit more. But one of the drivers with certainly, we had certain special higher discount agreements with certain Medicaid plans. Those have now expired. And so those would no longer be in play for the coming years.

是的。謝謝，蒂姆。所有偉大的問題。首先，關於醫療補助的增加。首先，重要的是要注意像這樣的品牌，30 億美元的淨銷售額，明顯更多的總銷售額，這裡的實際百分比變化並不大。儘管如此，我們並不能很好地理解為什麼醫療補助會出現更多。但其中一個驅動因素當然是，我們與某些醫療補助計劃簽訂了某些特殊的更高折扣協議。那些現在已經過期了。因此，這些在未來幾年將不再發揮作用。

And so I think overall, we expect to see the mix goes up and down year-to-year. But overall, we expect to see the mix stabilize back to what we've historically seen prior to this situation we had in 2022. In terms of formulary, it's largely in line with what we had in 2022. We see no significant shifts or changes in terms of formulary position, access. Overall, given the overall scheme of things when we look at gross, they're in line with 2022. So that's why we'll feel good in the U.S. that on an annual basis, we will be able to deliver sales that are in line with what we saw -- in 2023 with what we saw in 2022, and then the growth would come from the new indications.

因此，我認為總體而言，我們預計這一組合會逐年上升和下降。但總的來說，我們預計混合會穩定回到我們在 2022 年出現這種情況之前的歷史水平。就處方集而言，它與我們在 2022 年的情況基本一致。我們認為沒有重大轉變或變化在公式位置，訪問方面。總的來說，考慮到總體情況，當我們看總的時候，它們與 2022 年一致。這就是為什麼我們在美國感覺良好，每年我們將能夠實現符合要求的銷售額根據我們所看到的——2023 年我們在 2022 年看到的，然後增長將來自新的適應症。

Again, I just want to highlight that for the first half of this year, because of the fact we took all of that Medicaid charge in Q4, and when you lap the prior years, the base is not fully adjusted. So you are going to see a lower relative Cosentyx sales in Q1 and Q2 because of the base effects of taking all of that Medicaid rebate into quarter 4. But I think the bigger picture on this brand is our ability to deliver new indications, new formulations. That's really where we have to focus. And then the continued expansion in Asia and China as well as in Europe.

同樣，我只想強調今年上半年的情況，因為我們在第四季度承擔了所有的醫療補助費用，而當你把前幾年放在一邊時，基數並沒有完全調整。因此，由於將所有醫療補助回扣計入第 4 季度的基本效應，您將在第一季度和第二季度看到相對較低的 Cosentyx 銷售額。但我認為這個品牌的更大前景是我們提供新適應症、新配方的能力.這確實是我們必須關注的地方。然後在亞洲和中國以及歐洲繼續擴張。

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 系列。

On Slide 30, on Leqvio, there is a chart showing the sales that -- and the Entresto sales as well, the mostly sales. Do we have to understand that the Leqvio should continue to trend with the same pace as Entresto? Or, as you suggested last year, we should see an inflection later this year given the fact that we expand the number of sites that could prescribe the product? So some color on that would be helpful.

在幻燈片 30 上，在 Leqvio 上，有一張圖表顯示了銷售額——以及 Entresto 的銷售額，主要是銷售額。我們是否必須理解 Leqvio 應該繼續以與 Entresto 相同的速度發展趨勢？或者，正如您去年建議的那樣，鑑於我們擴大了可以開出該產品的網站數量，我們應該在今年晚些時候看到一個拐點？所以上面的一些顏色會有所幫助。

Yes. I think we just want to overall indicate that the launch is in line with other major cardiovascular launches, where we've been able to generate very large medicines, and you've seen how Entresto continues to perform. I don't exactly -- we continue to hope for the inflection point certainly in the second half of the year. It's hard to predict exactly when it would happen. There are a few things that give us confidence. We should see some acceleration in the back half of this year. One is the free trial offer program that we had rolled out will expire, and we hope that those patients will convert into paying patients in the second half.

是的。我認為我們只是想總體表明此次發布與其他主要心血管產品的發布一致，我們已經能夠生產非常大的藥物，而且您已經看到 Entresto 如何繼續發揮作用。我不完全是——我們繼續希望在今年下半年出現拐點。很難準確預測它何時會發生。有幾件事給了我們信心。我們應該會在今年下半年看到一些加速。一是我們推出的免費試用計劃將到期，我們希望這些患者在下半年轉為付費患者。

Second, with that 7,000-plus physicians that I mentioned, we expect to get greater depth in those physicians over time, which should also drive greater growth as well. We also see an increasing comfort with buy and bill versus the alternative injection centers. And as that happens as well, we generally see physician sites prescribing more of Leqvio because they can do it in-house without having to refer a patient out. So all of those would be the positive tailwinds we would see towards the second half of the year.

其次，對於我提到的 7,000 多名醫生，我們希望隨著時間的推移對這些醫生有更深入的了解，這也應該會推動更大的增長。與替代注射中心相比，我們還看到購買和賬單越來越舒適。當這種情況發生時，我們通常會看到醫生網站開出更多 Leqvio 的處方，因為他們可以在內部進行，而無需將患者轉診出去。因此，所有這些都將是我們將在今年下半年看到的積極順風。

I think broadly speaking, we feel comfortable with where consensus is on Leqvio for the full year 2023. And then our goal remains to make this into a very significant multibillion-dollar medicine over the coming 5 to 10 years.

我認為，從廣義上講，我們對 2023 年全年 Leqvio 的共識感到滿意。然後我們的目標仍然是在未來 5 到 10 年內將其變成一種非常重要的價值數十億美元的藥物。

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。

I have a question on oncology. Just obviously, there was a lot of emphasis on radioligand therapies, and that was highlighted some of the new and upcoming ones you have as well that are coming through Phase I/II. There are relatively few other sort of priorities in oncology highlighted within the pipeline. And so I wonder if you could still say, first of all, if you just sort of view your KRAS and the opportunity there, given also what we've seen develop in that market, but also ociperzumab, is that now discontinued? Or is it just delayed that you continue to evaluate TIGIT? And sort of more broadly, is this still an area which you could see further business development? Or do you think this is an area obviously less focus from Novartis?

我有一個關於腫瘤學的問題。很明顯，人們非常重視放射配體療法，並且強調了一些新的和即將到來的療法，這些療法也將通過 I / II 期。在管道中強調的腫瘤學其他類型的優先事項相對較少。所以我想知道你是否仍然可以說，首先，如果你只是看看你的 KRAS 和那裡的機會，考慮到我們在那個市場上看到的發展，還有 ociperzumab，它現在已經停產了嗎？還是您繼續評估 TIGIT 只是延遲了？更廣泛地說，這仍然是您可以看到進一步業務發展的領域嗎？或者您認為這是諾華公司明顯不太關注的領域？

Yes. So I think on oncology, I mean, it remains a huge focus for the company. 40% of our R&D budget is focused on developing the next wave of oncology medicine. Within solid tumors in addition to the radioligand therapies, where we have now a growing portfolio across neuroendocrine prostate, we have a range of other indications we're taking Lutathera into -- we have the anti-Integra, the bond basin. We recently are hopefully bringing in a folate as well. So we have a broad portfolio within RLT where we see a significant opportunity.

是的。所以我認為腫瘤學，我的意思是，它仍然是公司的一個巨大焦點。我們 40% 的研發預算專注於開發下一波腫瘤醫學。在實體瘤中，除了放射配體療法外，我們現在在神經內分泌前列腺方面擁有越來越多的產品組合，我們還有一系列其他適應症，我們正在將 Lutathera 納入其中——我們有抗 Integra，結合盆。我們最近也希望引入葉酸。因此，我們在 RLT 中擁有廣泛的投資組合，我們看到了巨大的機會。

We continue to also pursue the TIGIT through the deal we have with BeiGene, and we have that as an option deal. We also are assessing what other lines of therapy to take that TIGIT into given the competitive landscape, that's something we're actively evaluating.

我們還通過與百濟神州的交易繼續追求 TIGIT，我們將其作為一項選擇權交易。考慮到競爭格局，我們還在評估其他哪些治療方法可以將 TIGIT 納入其中，這是我們正在積極評估的事情。

And then in terms of other active programs that are in Phase III, certainly the KRAS and the KRAS G12C are continuing. Our overall perspective is a critical thing now is to demonstrate efficacy in a combination setting. We think we've seen now from the sales performance of the mono G12C inhibitors. While important for a certain group of patients that have the mutation, much more important is can you ultimately demonstrate tolerability and efficacy of the G12C with a PD-1, with a ship to with other agents. And that's something that we're working through to see. And that would really, I think, give us more confidence that this could be a very significant medicine.

然後就第三階段的其他活動項目而言，當然 KRAS 和 KRAS G12C 正在繼續。我們的整體觀點現在很關鍵，是要在組合環境中展示功效。我們認為我們現在已經從單一 G12C 抑製劑的銷售業績中看到了。雖然對於具有突變的特定患者群體很重要，但更重要的是您最終能否證明 G12C 與 PD-1 的耐受性和有效性，以及與其他藥物的合作。這就是我們正在努力看到的東西。我認為，這真的會讓我們更有信心，相信這可能是一種非常重要的藥物。

Now earlier stage within the NIBR portfolio, we have a range of different assets that we're pursuing. We have a few targeted protein degradation agents that are advancing now into Phase I/II, a couple of novel targets in non-small cell lung cancer as well as other solid tumors. So that whole space continues to progress. As you know, oncology has a high level of failure rate. So I don't want to oversell it, but I think we're certainly working to continue to find the next wave of solid tumors.

現在，在 NIBR 投資組合的早期階段，我們擁有一系列我們正在追求的不同資產。我們有一些靶向蛋白質降解劑，現在正進入 I/II 期，這是非小細胞肺癌和其他實體瘤的幾個新靶點。所以整個空間繼續進步。如您所知，腫瘤學的失敗率很高。所以我不想誇大其詞，但我認為我們肯定在努力繼續尋找下一波實體瘤。

And then we active -- are active in the BD&L space. And I think if we could find attractive assets within our core cancers: lung cancer, prostate cancer, the gastric GI cancers, et cetera, those are certainly things we would actively look at. I would say in hematology now between Scemblix, iptacopan, ianilumab, we have some pretty -- building on the legacy, of course, of Glivec, TASIGNA and PROMACTA, REVOLADE. We have a pretty good portfolio in hematology. And then, of course, with now YTV moving into the first-line setting in large B-cell lymphoma, it's a nice portfolio to continue to keep -- maintain our strength in hematology over time.

然後我們活躍——活躍在 BD&L 領域。我認為，如果我們能在我們的核心癌症中找到有吸引力的資產：肺癌、前列腺癌、胃 GI 癌等，這些肯定是我們會積極關注的事情。我想說，在血液學領域，現在在 Scemblix、iptacopan、ianilumab 之間，我們有一些漂亮的——建立在 Glivec、TASIGNA 和 PROMACTA、REVOLADE 的遺產之上。我們在血液學方面有很好的投資組合。然後，當然，隨著現在 YTV 進入大 B 細胞淋巴瘤的一線設置，這是一個很好的組合，可以繼續保持——隨著時間的推移保持我們在血液學方面的實力。

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。

Great. Thanks for the question. So can you maybe just give us a sense of what the team is doing to extend the IL-17 franchise beyond Cosentyx exclusivity in 2029? There's obviously a number of high-value immunology assets out there in development. We're just interested to know what Novartis is doing beyond that. And maybe if you could, would you mind commenting on how you see the HS landscape evolving going forward, given some of the data that we've seen for bimekizumab and then potential competitor moon-like as well.

偉大的。謝謝你的問題。那麼，您能否讓我們了解一下團隊正在做什麼，以在 2029 年將 IL-17 的特許經營權擴展到 Cosentyx 的獨家經營權之外？顯然有許多高價值的免疫學資產正在開發中。我們只是想知道諾華公司在這之外做了什麼。也許如果可以的話，考慮到我們已經看到的 bimekizumab 的一些數據以及潛在的類似月球的競爭者，您是否介意評論一下您如何看待 HS 景觀的發展。

Thanks, Seamus. So first on IL-17A and the Cosentyx portfolio overall, of course, I think we're actively working on and looking at Cosentyx, LOE 2029. We have additional patents that go into the 2030s, which will, of course, actively prosecute as well. We have a range of oral anti-immunological agents we're pursuing in-house. So oral IL-17A and as well as other oral agents. And of course, actively looking at external opportunities as well in that space, if we see compelling data. So I think I think that's going to be really critical for us to look at. But of course, we have time and something we'll work through over the coming years.

謝謝，西默斯。因此，首先是關於 IL-17A 和整個 Cosentyx 產品組合，當然，我認為我們正在積極研究 Cosentyx，LOE 2029。我們還有進入 2030 年代的其他專利，當然，這些專利將作為積極起訴出色地。我們有一系列內部正在研發的口服抗免疫藥物。所以口服 IL-17A 以及其他口服藥物。當然，如果我們看到令人信服的數據，也會積極尋找該領域的外部機會。所以我認為我認為這對我們來說真的很重要。但當然，我們有時間和一些我們將在未來幾年努力完成的事情。

I also would say that in immunology between ianalumab, remibrutinib as well as other programs we have now advancing through the pipeline, we're also prepared to pivot not to be -- not just focused on psoriasis, PSA and AS, but also try to move into -- really be a leader in areas like Sjogren's, SLE and other immunological illnesses, as you mentioned, like HS. For HS, our view is that our 52-week data is very compelling. We think this will really be a space where a long-term data is what really matters. We think our 52-week data relative to the TMS are very good. We're aware of other IL-17A is coming.

我還要說的是，在 ianalumab、remibrutinib 以及我們現在正在推進的其他項目之間的免疫學方面，我們也準備轉向不——不僅專注於牛皮癬、PSA 和 AS，而且還嘗試進入——真正成為 Sjogren 病、SLE 和其他免疫疾病領域的領導者，正如你提到的，如 HS。對於 HS，我們認為我們的 52 週數據非常有說服力。我們認為這真的是一個長期數據才是真正重要的空間。我們認為我們相對於 TMS 的 52 週數據非常好。我們知道其他 IL-17A 即將到來。

I think what's important to note is this is a very, very undertreated patient population. These patients generally have given up and generally are not coming in for therapy. So the real opportunity here is to get these patients to know that there are better therapies available, and that will create, I think, a large market opportunity, where multiple players can be successful Given that these agents are looking like they have better efficacy and safety than the anti-TM.

我認為需要注意的重要一點是，這是一個非常、非常缺乏治療的患者群體。這些患者通常已經放棄並且通常不會接受治療。所以這裡真正的機會是讓這些患者知道有更好的治療方法，我認為這將創造一個巨大的市場機會，多個參與者可以成功鑑於這些藥物看起來有更好的療效和安全性比抗TM。

(technical difficulty) anything to say about other mechanisms at the moment. In-house are pursuing other mechanisms as well against HS to try to make sure that we cover our bases. We have evaluation of our anti-CD40 ligand, we're evaluating remibrutinib, our BTK inhibitor. So we have a range of efforts looking at HS, and of course, we'll see which ones pan out in-house. (Operator Instructions)

（技術難度）目前關於其他機制有什麼要說的。內部也在尋求其他機制來對抗 HS，以確保我們覆蓋我們的基地。我們已經評估了我們的抗 CD40 配體，我們正在評估我們的 BTK 抑製劑瑞布替尼。因此，我們在 HS 方面做出了一系列努力，當然，我們會看看哪些在內部取得成功。 （操作員說明）

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。

Question is on Pluvicto. Looking at your patient access, Vas, demand clearly materially exceeds supply currently for the product in the U.S. Could you just outline your confidence of FDA approval for the mid and end year for the new facilities? Just given the recent track record of Leqvio plus you have a new facility, what is the risk of that dragging on? And connected to that, how should we think about the future competition from POINT and Lantheus with their (inaudible) in prostate?

問題是關於 Pluvicto。查看您的患者訪問，Vas，目前在美國的產品需求明顯超過供應。您能否概述一下您對 FDA 批准新設施年中和年底的信心？鑑於 Leqvio 最近的業績記錄加上你有一個新設施，拖延的風險是什麼？與此相關的是，我們應該如何考慮 POINT 和 Lantheus 與他們（聽不清）在前列腺方面的未來競爭？

Yes. I think with respect to the files we're ready to file, the site and we're in discussions with FDA to have filed the Millburn site. And the time we get the okay to file, there's a 4-month review clock for that additional facility.

是的。我認為關於我們準備提交的文件，網站，我們正在與 FDA 討論提交 Millburn 網站。當我們獲得批准提交時，該額外設施有 4 個月的審查時間。

Our Indianapolis facility with multiple large-scale automated lines, we plan to file in quarter 3 as well to the NDA. And again, it would be an addition of additional sites. So we would expect a 4-month approval time. And so we're doing everything we can to make that a reality. And we plan right now for those sites, our base plan is for those sites to come online this summer and then later on this year. And then we'd have adequate supply to fully meet the demand of the VISION population as well as the PSMAfore population.

我們的印第安納波利斯工廠擁有多條大型自動化生產線，我們計劃在第 3 季度也向 NDA 提交文件。同樣，這將是額外站點的添加。所以我們預計需要 4 個月的批准時間。因此，我們正在盡一切努力使之成為現實。我們現在正在為這些網站做計劃，我們的基本計劃是讓這些網站在今年夏天上線，然後在今年晚些時候上線。然後我們就有足夠的供應來完全滿足 VISION 人群和 PSMAfore 人群的需求。

Now I think in terms of the competition, it's important to note this is extremely difficult manufacturing. This is a just-in-time manufacturing that requires really logistics expertise. We currently source the entire U.S. market out of an Italian site and do it successfully. And we believe we've built up substantial know-how and expertise with the relevant sites to give us a strong competitive position. Now other players, of course, are going to come in and try to launch. The question will be do they have the same scale and expertise that Novartis does to be able to navigate that complexity and really ensure that they can meet the demand.

現在我認為就競爭而言，重要的是要注意這是極其困難的製造。這是一種準時制生產，需要真正的物流專業知識。我們目前從意大利網站採購整個美國市場並取得成功。而且我們相信我們已經在相關網站上積累了大量的專業知識和專業知識，使我們具有強大的競爭地位。當然，現在其他玩家也會進來嘗試推出。問題在於，他們是否擁有與諾華公司相同的規模和專業知識，能夠駕馭這種複雜性並真正確保他們能夠滿足需求。

So that's kind of our outlook right now. We feel good about -- by the middle of this year, we'll be in a very strong position to meet the supply. I would also note for Leqvio, because I noted your comment on that product, I mean, we have a large-scale line now that's up and running in Switzerland, which makes us the largest producer of siRNAs in the world. So I think we're good on gene therapy, RLT and sRNA manufacturing. We feel very good with the approach we've taken. And I think we're in a very good place on all 3 of them.

這就是我們現在的看法。我們感覺很好——到今年年中，我們將處於非常有利的地位來滿足供應。我還要注意 Leqvio，因為我注意到你對該產品的評論，我的意思是，我們現在有一條大規模生產線在瑞士啟動並運行，這使我們成為世界上最大的 siRNA 生產商。所以我認為我們在基因治療、RLT 和 sRNA 製造方面做得很好。我們對所採取的方法感到非常滿意。我認為我們在這三個方面都處於非常好的位置。

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

你的下一個問題來自高盛的 Keyur Parekh。

One big picture one for you've, Vas. With the proposed separation of Sandoz, kind of Novartis will become a focused innovative medicines company. Once that transaction is done, are you done with kind of the process of changing the shape and structure of Novartis? Or do you think there is more kind of you want to do relative to the size and the shape of the Innovative Medicines company that will be left at the end of the Sandoz transaction?

一張大圖，一張給你，瓦斯。隨著山德士的擬議分離，諾華將成為一家專注於創新藥物的公司。一旦交易完成，你是否完成了改變諾華公司的形狀和結構的過程？或者你認為相對於 Sandoz 交易結束時將留下的 Innovative Medicines 公司的規模和形態，你想做的事情更多嗎？

And just kind of linked with that, I know kind of Ronny team has been hiring kind of the higher -- kind of some people like Dr. Yang, et cetera. But just more broadly, how far along the process of building that kind of growth and strategy functions set under Ronny is kind of Novartis today? When do you think that might be done?

與此相關的是，我知道 Ronny 團隊一直在招聘更高級別的人才——比如 Yang 博士等。但更廣泛地說，在羅尼領導下建立的那種增長和戰略職能的過程中，今天的諾華有多遠？你認為什麼時候可以完成？

Yes. Thanks, Keyur. Broadly speaking, our strategy was to get to become a pure-play Innovative Medicines company, design the company in the right way. We started that journey in a principled way 5 years ago. Of course, there was a pandemic for 2.5 years in the middle of that, so it got a little more complex. But I think we have the right set up post the Sandoz spin with a geographic focus on the U.S. and ex U.S. and from a commercial standpoint, really committed and renewed leadership in R&D and then the strategy and growth function to really identify external and internal opportunities that can drive the growth.

是的。謝謝，基爾。從廣義上講，我們的戰略是成為一家純粹的創新藥物公司，以正確的方式設計公司。 5 年前，我們以有原則的方式開始了這一旅程。當然，中間有 2.5 年的大流行，所以它變得有點複雜。但我認為我們在 Sandoz 分拆後的設置是正確的，將地理重點放在美國和美國以外，從商業角度來看，真正致力於並重新領導研發，然後是戰略和增長職能，以真正識別外部和內部機會這可以推動增長。

So I think post that time period and post seeing through the transformation program we announced last year and the relevant restructuring, I think we'd be then in a position to really just focus on execution. We need to execute on our launches, execute on our pipeline, execute on our productivity, continue to generate that mid-single-digit sales growth and that attractive core margin over time. And then that becomes the core of what we do day in and day out, continuing to look at attractive external assets to add on over time.

因此，我認為在那個時間段之後，通過我們去年宣布的轉型計劃和相關重組，我認為我們將能夠真正專注於執行。我們需要執行我們的發布，執行我們的管道，執行我們的生產力，隨著時間的推移繼續產生中個位數的銷售增長和有吸引力的核心利潤率。然後這就成為我們日復一日工作的核心，繼續尋找有吸引力的外部資產以隨著時間的推移增加。

Ronny team is getting built out, I think, off to a strong start. A much more integrated -- the most integrated approach now that we've had that I'm aware of, at least in 20 years, is the R&D portfolio management, it all falls under one roof now in terms of how we look at the R&D portfolio, an integrated approach to taking commercial input into the earlier stages of research, much more focused on key TAs and being much more disciplined in saying no to projects that are of strategy. So I think all of that's coming together, it's been 4 or 5 months for Ronny, it's been 2 months for Fiona Marshall, but I feel really good that this is a great team that can deliver that innovation horsepower we're going to need as a pure-play company.

我認為，Ronny 團隊正在組建，開局良好。一種更加集成的方法——據我所知，至少在 20 年內，我們已經擁有的最集成的方法是研發組合管理，就我們如何看待研發組合，一種將商業投入納入研究早期階段的綜合方法，更加關注關鍵的 TA，並且更加自律地拒絕具有戰略意義的項目。所以我認為所有這些都在一起了，Ronny 已經 4 或 5 個月了，Fiona Marshall 已經 2 個月了，但我感覺非常好，這是一個偉大的團隊，可以提供我們需要的創新能力一家純粹的公司

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

你的下一個問題來自巴克萊銀行的 Emily Field。

I just wanted to ask a question about iptacopan. This U.S. filing in the first half of this year include both PNH trials. And then -- because I know you mentioned that you're running the switch study for the frontline patients as well. Just trying to get a sense of commercialization strategy across the PNH spectrum. And then just I know you have BTD for this asset, just how long of a regulatory review you might be expecting?

我只是想問一個關於 iptacopan 的問題。今年上半年美國提交的這份文件包括兩項 PNH 試驗。然後——因為我知道你提到過你也在為一線患者進行轉換研究。只是想了解 PNH 範圍內的商業化戰略。然後我知道你對這項資產有 BTD，你可能期望監管審查多長時間？

So with iptacopan, yes, we'll be following both studies, both the refractory and frontline study as part of the package, and that's aligned with FDA. We do have used a priority review voucher as well for this asset to really ensure that it's approved in a rapid time frame. Even though we had breakthrough therapy designation, we don't want to take any risks with respect to this particular filing to make sure that it happens as fast as possible.

因此，對於 iptacopan，是的，我們將關注這兩項研究，難治性研究和一線研究都作為一攬子計劃的一部分，並且與 FDA 保持一致。我們確實也為這項資產使用了優先審查憑證，以真正確保它在快速的時間框架內獲得批准。即使我們獲得了突破性療法認定，我們也不想為了確保盡快完成這一特定申請而承擔任何風險。

With respect to our overall strategy with iptacopan, when you look at this market, we believe that it's 60% to 70% of patients who, on current anti-C5 based therapies are not adequately controlled, and those patients could be switched to iptacopan based on the data we presented at ASH and assuming the final label supports it. And so that's a substantial opportunity for the medicine. We know that potentially up to 60% to 70% of diagnosed PNH patients are not on a therapy today. And they come on, I think, in a few different categories. Some are subclinical or not quite clinically severe enough. And the question is with a twice a year safe oral, is there an opportunity to get more of those patients on therapy because it may be physicians or patients were holding off wanting to be on regular infusions. So could an oral therapy open up that market.

關於我們對 iptacopan 的總體戰略，當你審視這個市場時，我們認為 60% 到 70% 的患者在目前的基於抗 C5 的治療中沒有得到充分控制，這些患者可以改用基於 iptacopan 的藥物基於我們在 ASH 上提供的數據，並假設最終標籤支持它。所以這對藥物來說是一個重要的機會。我們知道，今天可能有高達 60% 到 70% 的確診 PNH 患者沒有接受治療。我認為，它們分為幾個不同的類別。有些是亞臨床的或臨床上不夠嚴重。問題是每年兩次安全口服，是否有機會讓更多的患者接受治療，因為可能是醫生或患者不願接受定期輸液。口服療法也能打開這個市場。

I think there's a set of patients also who have gone back to taking transfusions, having now failed prior therapies. That's another opportunity. And then there's probably a set of patients as well that are just in the watch and wait mode. So that will be an opportunity for the medicine as well. So we think there's multiple places. It will take us time to drive this launch. So this will not be fast given the strength of the incumbent position. And then also that this -- a significant group of patients not on therapy has to get mobilized.

我認為還有一些患者已經重新開始接受輸血，現在之前的治療已經失敗了。那是另一個機會。然後可能還有一組患者處於觀察和等待模式。所以這對藥物來說也是一個機會。所以我們認為有多個地方。我們需要時間來推動這次發布。因此，鑑於現任職位的實力，這不會很快。然後還有這個 - 必須動員大量未接受治療的患者。

And we believe over time with the compelling data that we have and the recognition that a twice-a-day oral could be a really compelling option, we can build a very significant medicine on PNH, then expand into C3, IgAN, aHUS, IC-MPGN and then subsequent indications thereafter.

我們相信，隨著時間的推移，我們擁有令人信服的數據，並且認識到每天口服兩次可能是一個真正令人信服的選擇，我們可以在 PNH 上開發一種非常重要的藥物，然後擴展到 C3、IgAN、aHUS、IC -MPGN，然後是隨後的適應症。

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。

Just going back to Kesimpta and obviously, very strong. We're going to see another launch for another CD20 this year and coming around now from TG Therapeutics, obviously an IV, but lower price. How do you see that impacting Kesimpta this year? And maybe also we're going to see subcutaneous data, how do you see that as well in the future around the launch?

剛回到 Kesimpta，顯然非常強大。我們將在今年看到另一個 CD20 的另一次發布，現在來自 TG Therapeutics，顯然是 IV，但價格更低。你如何看待今年對 Kesimpta 的影響？也許我們還會看到皮下數據，您如何看待未來發射前後的數據？

Yes. Thanks, Richard. So the way we look at the MS market, the one, as I mentioned, you have 50% of patients that are not on B-cell therapies and 50% on B-cell therapy. So there's a substantial market opportunity just to get more patients in the first-line, first-switch setting on to high-efficacy B-cell therapy. So there's plenty of room for growth just for Kesimpta and getting some more of those patients.

是的。謝謝，理查德。所以我們看待 MS 市場的方式，正如我提到的，你有 50% 的患者沒有接受 B 細胞療法，50% 的患者接受 B 細胞療法。因此，有大量的市場機會可以讓更多的患者在第一線、第一時間切換到高效 B 細胞療法。因此，僅 Kesimpta 就有足夠的增長空間並吸引更多患者。

The second thing based on our understanding of the market is that there are sets of facilities and health systems that prefer infused medicines, and there are those that prefer providing patients subcu medicines. And we see those as very stable. So really, this market is a split market. You have a market of physicians who want to give infused medicines and there is a large proportion of the market who want to give patients the opportunity to have at-home subcu administration. Within that subcu, we don't see any at-home administration relevant competition for the coming years, and that's very much our focus area.

根據我們對市場的了解，第二件事是有一些設施和衛生系統更喜歡輸液藥物，還有一些更喜歡為患者提供微量藥物。我們認為這些非常穩定。所以說真的，這個市場是一個分裂的市場。你有一個想要輸液藥物的醫生市場，並且有很大一部分市場想要讓患者有機會在家進行亞細胞給藥。在該 subcu 中，未來幾年我們看不到任何與家庭管理相關的競爭，這是我們非常關注的領域。

Within the IV segment, there is now competition and I think that competitive dynamic will be an important one for us to observe. And I think to your point, Richard, will the opportunity of having subcu physician-administered medicines expand the number of centers that might be interested in a physician-administered approach, we don't know. Nonetheless, the market opportunity ahead of us, with the 50% of patients not on B-cell therapies and the substantial number of physicians who prefer providing an at-home administration, that's the opportunity for this medicine, and that will give us plenty of room to grow over the coming period.

在 IV 部分，現在存在競爭，我認為競爭動態將是我們觀察的一個重要方面。我認為，理查德，就你的觀點而言，是否有機會讓 subcu 醫生管理的藥物擴大可能對醫生管理的方法感興趣的中心數量，我們不知道。儘管如此，我們面前的市場機會是，50% 的患者沒有接受 B 細胞療法，而且有大量醫生更喜歡提供在家給藥，這就是這種藥物的機會，這將為我們帶來很多未來一段時期的增長空間。

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。

Just going back to Leqvio. Vas, you briefly touched on buy and bill. I just wonder if you could give us a little bit more detail on the progress you're making there. I ask because, on one hand, there was a fairly negative article earlier in the month on like to (inaudible) but on the other hand, we see in September and December last year, quite a significant uptick in traffic to the Leqvio access website. So I just wonder if you could give us the latest picture there.

剛回到Leqvio。 Vas，您簡要地談到了購買和賬單。我只是想知道您是否可以向我們提供更多關於您在那裡取得的進展的細節。我問是因為，一方面，本月早些時候有一篇關於 like to（聽不清）的相當負面的文章，但另一方面，我們看到去年 9 月和 12 月，Leqvio 訪問網站的流量顯著增加.所以我只是想知道你是否可以給我們那裡的最新照片。

Thanks, Simon. Look, there's no question that buy and bill is a new approach that cardiologists need to understand and get implemented to their office. That said, we know there are many specialties that have successfully done that, ophthalmology, oncology, rheumatology, neurology. So this is something that can be done. Is it -- does it take time? Yes. Do you have to work through many hurdles? Yes. Do you have to get all the staff to understand a new approach? Yes, absolutely, but it can all be done.

謝謝，西蒙。看，毫無疑問，購買和賬單是心髒病專家需要了解並在他們的辦公室實施的一種新方法。也就是說，我們知道有許多專業已經成功地做到了這一點，眼科、腫瘤學、風濕病學、神經病學。所以這是可以做到的。這需要時間嗎？是的。你必須克服許多障礙嗎？是的。您是否必須讓所有員工都了解新方法？是的，絕對可以，但這一切都可以做到。

And as I noted, now that we have over 7,000 physicians that have taken action on Leqvio, 1,800 facilities ordering Leqvio. A steady increase in conversion from facilities that were previously using alternative injection centers to now implementing buy and bill in their facility for Leqvio. I think we're getting to a place now where physicians are getting more and more comfortable with the concept. And what we generally see is once a physician has one patient go through the process and they understand that it is something that's manageable, then it becomes something relatively straightforward for their office and then they take it on relatively quickly.

正如我所指出的，現在我們有超過 7,000 名醫生對 Leqvio 採取了行動，1,800 家機構訂購了 Leqvio。從以前使用替代注射中心的設施到現在在其設施中為 Leqvio 實施購買和計費的轉化率穩步增加。我認為我們現在已經到了一個地步，醫生對這個概念越來越滿意。我們通常看到的是，一旦醫生讓一名患者完成了這個過程，並且他們明白這是可以管理的事情，那麼這對他們的辦公室來說就變得相對簡單，然後他們就會相對迅速地接受它。

So we have to get up that curve, but we're seeing, I think, positive trends. And we'll just keep working through it, keep also hopefully having clinics be able to educate one another about the experience of how buy and bill ultimately works and get that further implemented. So I wouldn't read too much. And you can always find probably a physician to tell you any process is onerous and terrible. But I think broadly, when we look at a large-scale data set, we see steady progress on this front.

所以我們必須走上這條曲線，但我認為我們看到了積極的趨勢。我們將繼續努力，也希望診所能夠就購買和計費最終如何運作的經驗相互教育，並進一步實施。所以我不會讀太多。你總能找到一位醫生告訴你任何過程都是繁重和可怕的。但我認為，從廣義上講，當我們查看大規模數據集時，我們會看到這方面的穩步進展。

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。

A question for Harry, please. Just going back to the Sandoz operating expenses into 2023. I mean that's the biggest delta that your consensus really looking at the composition of numbers for this year. Harry, how much of these expenses are standup costs and how much is sort of prepping for manufacturing shift as well? This just seems a meaningful amount that is coming into the P&L. Is that purely just separation costs? Or is that already including sort of longer-term expenses that already hit 2023?

請問哈利一個問題。回到 Sandoz 到 2023 年的運營支出。我的意思是，這是你的共識真正關註今年數字構成的最大增量。哈里，這些費用中有多少是固定成本，還有多少是為生產轉移做準備的？這似乎是進入損益表的一個有意義的數額。那純粹只是分離成本嗎？還是已經包括了一些已經達到 2023 年的長期支出？

Yes. Thank you, Michael. So overall, I would say, if we take out these standup and transitionary costs, the core operating in Sandoz in '23 would be flat. So it's a low double-digit decline comes from that. If you think about, right, Sandoz delivered $1.9 billion core operating in'22, so we talk about roughly plus/minus $200 million of cost block. Out of that $200 million, about $70 million to $90 million will be real standup costs, corporate costs and so on that Sandoz needs to operate as a separate public company. And the other half, if you will, will go away over time, as the fully transitioned to a public company. That would naturally go away as these transition costs are not any more needed over -- after a couple of years.

是的。謝謝你，邁克爾。所以總的來說，我想說，如果我們去掉這些站立和過渡成本，23 年 Sandoz 的核心業務將持平。因此，這是一個較低的兩位數下降。如果你想一想，山德士在 22 年交付了 19 億美元的核心業務，所以我們談論大約正負 2 億美元的成本塊。在這 2 億美元中，大約 7000 萬至 9000 萬美元將是真正的站立成本、公司成本等，山德士需要作為一家獨立的上市公司運營。而另一半，如果你願意的話，會隨著時間的推移而消失，因為它已經完全過渡到一家上市公司。這自然會消失，因為在幾年之後不再需要這些過渡成本。

Of course, also the corporate cost -- there will be corporate costs. But clearly, Sandoz has plans to reach in the midterm the mid-20s margin by then streamlining the overall operations, SG&A structures as they are a stand-alone company. So I hope that gives you a bit more flavor on that guidance for this year, which really should be a trough year. And then after the separation, relatively quickly come off that, including, of course, taking over transitional service costs, like for IT over time, quite quickly, usually maximum 2 years on such services.

當然，還有公司成本——會有公司成本。但顯然，Sandoz 計劃通過精簡整體運營、SG&A 結構，在中期達到 20 年代中期的利潤率，因為它們是一家獨立的公司。所以我希望這能讓你對今年的指導有更多的了解，這真的應該是低谷的一年。然後在分離之後，相對較快地取消它，當然包括接管過渡服務成本，就像 IT 隨著時間的推移，很快，通常在此類服務上最多 2 年。

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

你的下一個問題來自德意志銀行的 Emmanuel Papadakis。

Perhaps I'll take one on Kisqali. You've reiterated the over $3 billion pre-sales potential for the edge of an indication. So perhaps you could just help us understand how important do you think a clinically meaningful benefit in both of the 2 key subpopulations in the trial as intermediate risk and higher risk in terms of realizing that potential that is positive? And how would you define clinically meaningful in terms of the absolute relative DFS benefit in that population? And indeed, is that something you actually disclose with the headline or have to wait until details are presented?

也許我會在 Kisqali 上拍一張。您重申了適應症邊緣的超過 30 億美元的預售潛力。因此，也許您可以幫助我們了解您認為在實現積極潛力方面，作為中等風險和較高風險的試驗中的兩個關鍵亞群具有臨床意義的獲益有多重要？您如何根據該人群的絕對相對 DFS 獲益來定義臨床意義？事實上，這是您實際在標題中披露的內容還是必須等到詳細信息出現？

Yes. Thanks, Emmanuel. So the trial right now is overall designed for an endpoint across both patient populations. And so there -- in order to hit the primary endpoint, we need to hit across all populations. Now the question would be, would FDA parse the data and say that it was driven by the high-risk population and then potentially take a different approach, we can't judge. But the way designed and powered the study is across the entire group. And so from a prespecified analysis on the primary endpoint, it would be for both the intermediate and the high risk, of course, with the relevant secondary end points.

是的。謝謝，伊曼紐爾。因此，目前的試驗總體上是針對兩個患者群體的終點而設計的。因此——為了達到主要終點，我們需要覆蓋所有人群。現在的問題是，FDA 是否會分析數據並說它是由高風險人群驅動的，然後可能採取不同的方法，我們無法判斷。但是設計和推動研究的方式是在整個團隊中進行的。因此，根據對主要終點的預先指定的分析，這將是針對中等風險和高風險的，當然，還有相關的次要終點。

I'd also note that we've aligned with FDA that key for us is to show no detriment in OS, as long as we can demonstrate no detriment in OS at the time of that readout, that would be the case. So I think you could expect a headline on, whenever it comes, on the IDFS. And then if relevant OS or not relevant the -- we would not say anything on the OS. And then we'd have to have the discussion with the agency to determine how they would like us to cut the data. From our competitor data, there was a threshold that was applied for a certain subpopulation Ki-67 and then later adjusted. So these are all things that we'll have to determine as part of the review process.

我還要指出，我們已經與 FDA 保持一致，我們的關鍵是不顯示對 OS 的損害，只要我們能夠證明在讀出時對 OS 沒有損害，情況就是如此。因此，我認為無論何時，您都可以期待關於 IDFS 的頭條新聞。然後，如果操作系統相關或不相關——我們不會在操作系統上說什麼。然後我們必須與該機構進行討論，以確定他們希望我們如何削減數據。根據我們的競爭對手數據，有一個閾值適用於特定的 Ki-67 亞群，然後進行了調整。因此，這些都是我們在審核過程中必須確定的所有內容。

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。

It's Mark Purcell from Morgan Stanley. On iptacopan, first, could you help us understand, when you say the 9-month analysis could potentially support U.S. Subpart H filing, how should we think about the sort of probability of moving forward at that point versus, obviously, out just of 2025 or so and slowing progression of IgAN before you can approach the FDA with your package?

我是摩根士丹利的 Mark Purcell。關於 iptacopan，首先，您能否幫助我們理解，當您說 9 個月的分析可能支持美國 H 子部分申請時，我們應該如何考慮在那個時候向前推進的可能性，顯然，僅在 2025 年之後左右並減緩 IgAN 的進展，然後才能將您的包裹提交給 FDA？

And then sort of related to that, obviously, a much bigger population in IgAN versus PNH and C3G, aHUS, et cetera, should we think about sort of population of the 185,000 patients you estimate with IgAN, which would be a target hill? Or would you sort of launch this as a completely separate brand? I'm trying to think about what Novartis' broad ambitions might be to build out a portfolio of primary care and rare renal assets given your commercial capabilities across the platform.

然後與此相關，很明顯，IgAN 的人口比 PNH 和 C3G、aHUS 等要大得多，我們是否應該考慮您估計的 185,000 名 IgAN 患者的人口，這將是一個目標山？或者你會把它作為一個完全獨立的品牌推出嗎？考慮到您在整個平台上的商業能力，我正在考慮諾華公司建立初級保健和稀有腎臟資產組合的廣泛抱負。

Yes. Thanks, Mark. So first on the endpoint for IgAN. We saw in the Phase II data, Phase IIb data, I think (technical difficulty)

是的。謝謝，馬克。所以首先是 IgAN 的端點。我們在 II 期數據中看到，IIb 期數據，我認為（技術難度）

Reduction in proteinuria across the very statistical analysis that we've done. And that's the basis for us designing the Phase III study. So we feel good that if we hit the required slope of reduction that we target that, that would allow us to file with the FDA. Though I imagine it will also come down to the totality of the data. But certainly, our base case is that if we hit the primary end point on proteinuria, that should give us the basis to file. And then of course, we would look at eGFR and other endpoints in 2025 that would be more meaningful after further follow-up.

通過我們所做的統計分析，蛋白尿減少。這是我們設計 III 期研究的基礎。因此，我們感覺很好，如果我們達到了我們的目標所需的減少斜率，那將允許我們向 FDA 提交文件。儘管我想這也將歸結為數據的整體性。但可以肯定的是，我們的基本情況是，如果我們達到了蛋白尿的主要終點，那應該為我們提供了提交的依據。然後當然，我們會在 2025 年查看 eGFR 和其他終點，這些終點在進一步跟進後會更有意義。

Broadly speaking, for our Factor B (technical difficulty)

從廣義上講，對於我們的因素 B（技術難度）

focus on PNH, C3G, aHUS, IC-MPGN, called the gluten disease and the related spectrum of illnesses, when we're in a more common illness like IgA nephropathy, our focus is on more severe patients to be able to maintain the ultra-rare pricing. We do have follow-on Factor B inhibitors that we plan to take forward in broader indications. You'll know that we do have a program for iptacopan evaluated in geographic atrophy and related retinal diseases. And if successful, we would actually use the backup compound for those broad indications, and that's how we're thinking about splitting out across the whole factor being enterprise.

專注於 PNH、C3G、aHUS、IC-MPGN，稱為麩質病和相關疾病譜，當我們處於更常見的疾病如 IgA 腎病時，我們的重點是更嚴重的患者，以便能夠維持超-罕見的定價。我們確實有後續的 B 因子抑製劑，我們計劃將其用於更廣泛的適應症。您會知道我們確實有一個針對 iptacopan 的項目，該項目在地圖樣萎縮和相關視網膜疾病中進行了評估。如果成功，我們實際上會使用備用化合物來處理這些廣泛的適應症，這就是我們考慮在整個企業中拆分的方式。

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。

It's just another one on Pluvicto. You've outlined obviously, you'll have manufacturing capacity to allow you to address the majority of the PSMAfore population by 2024. Could you talk about the other hurdles and limitations on your ability to penetrate that population, including referral patents, proportion of patients care in the community and access to nuclear medicine facility, just so that you can help us scope out the opportunity?

這只是 Pluvicto 上的另一個。您已經清楚地概述了，到 2024 年，您將擁有製造能力來解決大多數 PSMAfore 人群的問題。您能否談談您滲透該人群的能力的其他障礙和限制，包括轉診專利、患者比例社區關懷和核醫學設施的使用權，以便您可以幫助我們尋找機會？

Yes. Richard, what we've seen thus far is there's about 500 facilities we believe we would need to be able to provide Pluvicto, at least in the U.S. market, to reach the demand -- the potential basin population across the 3 indications that we have. We're able to -- currently servicing a little over 200 of them, and we expect that to expand over time. I think what's going to be the next challenge because the demand, as we've noted throughout the call, much higher than we expected, and I think folks on the call expected, frankly, is actually having -- the centers have enough infusion chairs to be able to provide the therapy to enough patients.

是的。理查德，到目前為止我們所看到的是，我們認為我們需要能夠提供 Pluvicto 的大約 500 個設施，至少在美國市場，以滿足需求——我們擁有的 3 個跡像中的潛在流域人口.我們能夠——目前為其中的 200 多家提供服務，我們預計隨著時間的推移會擴大。我認為下一個挑戰將是什麼，因為正如我們在整個電話會議中所指出的那樣，需求遠高於我們的預期，而且我認為坦率地說，參加電話會議的人們實際上有 - 中心有足夠的輸液椅能夠為足夠多的患者提供治療。

So that's the next constraint beyond once we believe our supply constraint later in the middle of this year to then work with the centers to have a better estimate of what the number of patients they think they will need to provide radioligand therapy to a day and ensure they have adequate chair or bed capacity to be able to do that. Because I think that will be, as we get into broader and broader patient populations, that will be the next constraint we'll have to then work through. There seems to be a lot of enthusiasm in the urology and nuclear medicine community to do that, so I expect it will happen. But that's something we're going to have to work through over the coming quarters.

因此，這是下一個限制條件，一旦我們認為我們在今年年中晚些時候出現供應限制，然後與中心合作，以更好地估計他們認為每天需要提供放射配體治療的患者人數，並確保他們有足夠的椅子或床位來做到這一點。因為我認為，隨著我們進入越來越廣泛的患者群體，這將是我們必須克服的下一個限制。泌尿外科和核醫學界似乎對此充滿熱情，所以我預計它會發生。但這是我們在未來幾個季度必須解決的問題。

Just opening Steve's line.

剛打開史蒂夫的電話。

I assume you're calling on Steve Scala. So I'm just wondering, what is your specific assumption for the profile of Merck's oral PCSK9 for which data is coming very near term, in terms of both its LDL lowering and its safety? I assume your view is very cautious, which supports your high enthusiasm for Leqvio, but what sort of role do you think an oral PCSK9 ultimately could have in this marketplace? .

我假設您正在拜訪 Steve Scala。所以我只是想知道，就其低密度脂蛋白降低和安全性而言，您對默克口服 PCSK9 的概況有何具體假設，其數據即將到來？我認為您的觀點非常謹慎，這支持了您對 Leqvio 的高度熱情，但您認為口服 PCSK9 最終會在這個市場中發揮什麼樣的作用？ .

Yes. Thanks, Stephen. I'm glad you asked that question. Our view -- and we had an oral PCSK9 program, which we've deprioritized. We are pivoting cardiovascular research into -- in Novartis and to infrequently administered siRNA, ASOs, et cetera, to get to -- first, as you know, we have PCSK9, we have combination programs, of course, we have Lp(a), follow-on programs with various combinations. And the goal would be to say, can you get to combinations at 6 months or long-acting at 1 year, with the belief that over the last 25 years, we've learned that compliance to orals in this market is low. Statins are 30%, other therapeutics are in a similar range.

是的。謝謝，斯蒂芬。很高興你問了這個問題。我們的觀點——我們有一個口頭 PCSK9 程序，我們已經取消了它的優先級。我們正在將心血管研究轉向——在諾華公司和不經常使用的 siRNA、ASO 等，以達到——首先，如你所知，我們有 PCSK9，我們有聯合計劃，當然，我們有 Lp(a) ，具有各種組合的後續程序。目標是說，你能否在 6 個月時獲得聯合用藥或在 1 年時獲得長效藥物，相信在過去 25 年中，我們了解到這個市場對口服藥物的依從性很低。他汀類藥物佔 30%，其他療法也處於相似的範圍內。

And if we really want to tackle cardiovascular disease scale, we need to get to infrequent administration. So we have Leqvio as a starting point. We're going to work very hard to extend past -- not get the 9 to 13. But we're anyway going to have life cycle management working on long-acting Leqvio, working on combinations with Leqvio. And our goal will be very much to have a combination sRNAs that can cover the relevant mechanisms of action for cholesterol lowering, so that patients won't need oral drugs anymore. Because we think that's where medicine is heading and we think that's what sRNAs, long-acting ASOs and similar technologies can deliver. So hence, we deprioritized oral systematically on cardiovascular at Novartis and focus on this next wave of technologies and therapies.

如果我們真的想解決心血管疾病的規模，我們需要減少給藥頻率。所以我們以 Leqvio 作為起點。我們將非常努力地工作以延長過去——而不是朝九晚九。但無論如何，我們將在長效 Leqvio 上進行生命週期管理，與 Leqvio 進行組合。我們的目標將是擁有一種組合 sRNA，它可以涵蓋降低膽固醇的相關作用機制，這樣患者就不再需要口服藥物了。因為我們認為這就是醫學的發展方向，我們認為這就是 sRNA、長效 ASO 和類似技術可以提供的東西。因此，我們在諾華公司係統地取消了心血管方面的口服優先權，並專注於下一波技術和療法。

All right. Very good. Thank you all for joining, and we look forward to updating you further at quarter 1. Take care.

好的。非常好。感謝大家的加入，我們期待在第一季度為您提供進一步的更新。保重。

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。