Novartis AG (NVS) 2021 Q4 法說會逐字稿

Good morning and good afternoon. And welcome to the Novartis Q4 and Full Year 2021 Results Release Conference Call and Live Webcast. (Operator Instructions) The conference is being recorded. (Operator Instructions) A recording of the conference call, including the Q&A session, will be available on our website shortly after the call ends. (Operator Instructions)

早上好，下午好。歡迎來到諾華第四季度和 2021 年全年業績電話會議和網絡直播。 （操作員說明）正在錄製會議。 （操作員說明）電話會議的錄音，包括問答環節，將在電話會議結束後不久在我們的網站上提供。 （操作員說明）

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

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

Thank you very much. And good morning and good afternoon, everybody. A big thank you for joining us today on our Q4 '21 and full year '21 results.

非常感謝你。大家早上好，下午好。非常感謝您今天加入我們，了解我們的 21 年第四季度和 21 年全年業績。

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.

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

With that, I'll now hand the call to Vas.

有了這個，我現在將電話交給 Vas。

Thank you, Samir, and thank you, everyone, for joining today's conference call. Moving to Slide 3. With me today, I have Harry, Marie-France, Susanne, John Richard, Karen and of course you've already heard from Samir.

謝謝你，薩米爾，謝謝大家參加今天的電話會議。轉到幻燈片 3。今天和我在一起的有 Harry、Marie-France、Susanne、John Richard、Karen，當然你已經收到了 Samir 的消息。

Now turning to Slide 5. And before moving into the quarter, I'd like to just make a few overarching statements about the company, our direction and our overall profile. We believe we continue to present an attractive profile for investors, a clear strategy as a focused medicines company, powered by technology and technology platforms which we believe will define the future of our sector and the future of medicine; an attractive growth profile, where we're confident in the 4% plus sales CAGR that we've guided to, and with the goal to be above peer median beyond 2026, and an aspiration to be in the high 30s IM margin, which we're well on our way towards; a strong mid- and late-stage portfolio with over 20 assets with significant peak sales potential; platform leadership, which we continue to work towards across multiple defining platforms in the sector; and a balanced approach to capital allocation, which I'll speak more about in a few slides.

現在轉到幻燈片 5。在進入本季度之前，我想就公司、我們的方向和我們的整體形像做一些總體陳述。我們相信，我們將繼續為投資者展示具有吸引力的形象，作為一家專注的藥品公司的明確戰略，由我們相信將定義我們行業的未來和醫藥未來的技術和技術平台提供支持；具有吸引力的增長概況，我們對我們所指導的 4% 以上的銷售複合年增長率充滿信心，目標是在 2026 年之後高於同行中位數，並且渴望達到 30 多歲的高 IM 利潤率，我們'我們正朝著前進的方向前進；強大的中後期投資組合，擁有超過 20 種資產，具有顯著的峰值銷售潛力；平台領導力，我們將繼續在該領域的多個定義平台上努力實現這一目標；以及平衡的資本配置方法，我將在幾張幻燈片中詳細介紹。

Now moving to Slide 6. We continued to evolve and sharpen our strategy. We are continuing to look at where to play, with a particular focus now on 4 key therapeutic areas with 2 additional therapeutic areas we're selectively participating in; focus on 4 key geographies while always evaluating our geographic footprint; and aspiration to transform Sandoz; 5 key priorities on how we win, which we continue to focus on and believe, will enable us to outperform the sector over time; and a clear aspiration to be a top 3 innovator; be in the high 30s in terms of our IM margin; an attractive return on invested capital; and continuing to be one of the leaders in material ESG factors in the biopharmaceutical sector.

現在轉到幻燈片 6。我們繼續發展和加強我們的戰略。我們將繼續研究在哪裡進行比賽，現在特別關注 4 個關鍵治療領域以及我們選擇性參與的 2 個額外治療領域；專注於 4 個關鍵地區，同時始終評估我們的地理足跡；以及改造山德士的願望；關於我們如何取勝的 5 個關鍵優先事項，我們將繼續關注並相信，這將使我們能夠隨著時間的推移超越該行業；以及成為前三名創新者的明確願望；就我們的 IM 利潤率而言，處於 30 年代的高位；有吸引力的投資回報；並繼續成為生物製藥領域物質 ESG 因素的領導者之一。

Then moving to Slide 7. When you look at our track record on our financial performance, our track record, particularly on IM, has been solid. IM sales in the last 4 years have grown 7%. IM core operating income has grown 13%, which is amongst the highest in the sector. Our IM core margin has now reached 36.2%. And our group free cash flow continues to perform well, and we continue to look at improving our free cash flow generation as a firm. So I think this demonstrates that we are delivering against the goals we set ourselves, and we plan to continue to do that in the years to come.

然後轉到幻燈片 7。當您查看我們在財務業績方面的往績記錄時，我們的往績記錄，特別是在 IM 方面，一直很穩固。過去 4 年的 IM 銷售額增長了 7%。 IM 核心營業收入增長 13%，位居行業前列。我們的 IM 核心利潤率現已達到 36.2%。我們的集團自由現金流繼續表現良好，我們繼續著眼於改善我們作為一家公司的自由現金流產生。所以我認為這表明我們正在實現我們為自己設定的目標，我們計劃在未來幾年繼續這樣做。

Then moving to Slide 8. Just as a reminder, over the coming years, we expect to grow that -- at that 4% or better rate, overcoming the estimated $9 billion of potential generic impact that we could have in this period, with a series of strong growth drivers: 6 major assets which we believe will have multibillion-dollar potential, a strong pipeline which would then be added on top, leading to that 4%. And of course, depending on when the Entresto LOE falls, the potential to do even better.

然後轉到幻燈片 8。提醒一下，在未來幾年，我們預計會以 4% 或更高的速度增長，以克服我們在此期間可能產生的估計 90 億美元的潛在通用影響，一系列強勁的增長動力：我們認為將具有數十億美元潛力的 6 項主要資產，然後將增加一個強大的管道，從而達到 4%。當然，取決於 Entresto LOE 何時下降，有可能做得更好。

So now turning to Q4 and on Slide 9. In Q4, we delivered strong performance across our value drivers. Growth was plus 6% in the quarter, with IM reaching 7% of sales productivity, continued with group core operating up 12%, IM core operating income up 15%. I think demonstrating that productivity power we have within the company. I'll come back to innovation, but we had important innovation milestones in the quarter. And in terms of our progress on ESG, we had improved scores on multiple ESG metrics, including the MSCI, and continued our progress on environment and human rights.

所以現在轉向第四季度和幻燈片 9。在第四季度，我們在價值驅動因素方面表現出色。本季度增長 6%，IM 達到銷售生產力的 7%，集團核心業務繼續增長 12%，IM 核心業務收入增長 15%。我認為證明我們在公司內部擁有的生產力。我會回到創新，但我們在本季度有重要的創新里程碑。在 ESG 方面的進展方面，我們提高了包括 MSCI 在內的多個 ESG 指標的得分，並繼續在環境和人權方面取得進展。

So focusing in on growth and turning to Slide 10. Our key growth drivers grew 24% in the quarter and now represents more than half of the IM sales. We were pleased with the performance on our growth brands, and Marie-France and Susanne will go through that in a bit more detail. And as you can see on the right-hand side of the slide, the steady increase we've had of these growth drivers, constituting more and more of our sales, demonstrating the replacement power of our core sales base that we have within the company.

因此，專注於增長並轉向幻燈片 10。我們的主要增長動力在本季度增長了 24%，現在佔 IM 銷售額的一半以上。我們對增長品牌的表現感到滿意，Marie-France 和 Susanne 將更詳細地介紹這一點。正如您在幻燈片右側看到的那樣，這些增長動力的穩步增長構成了我們越來越多的銷售額，展示了我們在公司內部擁有的核心銷售基礎的替代能力.

Now moving to Slide 11. Across the 6 key brands that we're hyper-focused on, we saw a double-digit growth, Cosentyx growing 17%, Entresto at 40%, Zolgensma 46% and Kisqali at 36%. Kesimpta is off to a very strong start on its first full launch year. Marie-France will go through that in a bit more detail, but we saw a very strong share gain. And Leqvio is in a build year this year. And we expect over the course of this year to consistently build momentum towards an inflection point in the '23 and beyond time period. As you can see and as we highlighted in our R&D Day, these brands are protected, outside of Entresto, into the late 2020s or into the 2030s, forming a strong foundation for the company which we can build on with our pipeline assets.

現在轉到幻燈片 11。在我們高度關注的 6 個關鍵品牌中，我們看到了兩位數的增長，Cosentyx 增長了 17%，Entresto 增長了 40%，Zolgensma 增長了 46%，Kisqali 增長了 36%。 Kesimpta 在其第一個完整的發布年有一個非常強勁的開端。 Marie-France 將更詳細地介紹這一點，但我們看到了非常強勁的份額增長。 Leqvio 今年正處於建設年。我們預計在今年的整個過程中，將始終如一地為 23 年及以後的時間段內的拐點建立動力。正如您所看到的以及我們在研發日中強調的那樣，這些品牌在 Entresto 之外受到保護，直到 2020 年代後期或 2030 年代，為公司奠定了堅實的基礎，我們可以利用我們的管道資產繼續發展。

Now moving to Slide 12. And when you take a geographic view of the business, we had consistent growth across U.S., Europe and China in innovative medicines, driven by different brands in each case. But in the U.S., we continue to show consistent growth, and we have an aspiration to become a top 5 player in the U.S. over time. In Europe, we remain the largest pharmaceuticals company, and again, are looking forward now to launching Kesimpta and Leqvio in the market to continue that growth dynamic.

現在轉到幻燈片 12。當您從業務的地理角度來看，我們在美國、歐洲和中國的創新藥物方面持續增長，這在每種情況下都是由不同的品牌推動的。但在美國，我們繼續保持持續增長，我們渴望隨著時間的推移成為美國前 5 名玩家。在歐洲，我們仍然是最大的製藥公司，現在再次期待在市場上推出 Kesimpta 和 Leqvio 以繼續這種增長動力。

In China, we have been one of the most consistent-growing companies, in the high teens over recent years. And we are confident that we will get to our goal of over $4 billion in sales in China by 2025. And we'll go through a little bit more on some of the dynamics in China in quarter 4. But we've already seen a recovery from some of the slowdown we saw in Q4 due to the buying patterns, the NRDL listings and some of the other considerations that we have. And we'll speak more about that in the conference call.

在中國，我們一直是近年來發展最穩定的公司之一。而且我們有信心，到 2025 年，我們將在中國實現超過 40 億美元的銷售額的目標。我們將在第 4 季度進一步了解中國的一些動態。但我們已經看到由於購買模式、NRDL 列表和我們擁有的其他一些考慮因素，我們在第四季度看到的一些放緩中復蘇。我們將在電話會議中對此進行更多討論。

Now moving to Slide 13 and turning to innovation. We had multiple milestones in the quarter. The approvals of Scemblix in the U.S. and Leqvio in the U.S., importantly, from an approval standpoint. Additional submissions, including Lu-PSMA-617 in Europe, as well as alpelisib in PROS, an opportunity for us to take on a very high unmet need, though small indication.

現在轉到幻燈片 13 並轉向創新。我們在本季度有多個里程碑。重要的是，從批准的角度來看，Scemblix 在美國的批准和 Leqvio 在美國的批准。其他提交，包括歐洲的 Lu-PSMA-617，以及 PROS 中的 alpelisib，我們有機會應對非常高的未滿足需求，儘管跡像很小。

Our readouts. Multiple readouts in the quarter, positive data for Cosentyx in hidradenitis suppurativa as well as with IV administration in psoriatic arthritis. Ligelizumab read out as well, positive versus placebo, non-inferior versus Xolair. We continue to evaluate the path forward for ligelizumab. And YTB and PHE, which I'll speak more about as well, in terms of our novel CAR-T platform. We began our Phase III studies for remibrutinib, both in multiple sclerosis and CSU, as well as with ligelizumab in food allergy and cold-induced urticaria.

我們的讀數。本季度的多次讀數，Cosentyx 在化膿性汗腺炎中的陽性數據以及在銀屑病關節炎中的 IV 給藥。 Ligelizumab 也讀出，陽性與安慰劑相比，非劣效與 Xolair。我們繼續評估 ligelizumab 的前進道路。就我們新穎的 CAR-T 平台而言，還有 YTB 和 PHE，我也會更多地談論它們。我們開始了瑞布替尼的 III 期研究，包括多發性硬化症和 CSU，以及 ligelizumab 治療食物過敏和感冒引起的蕁麻疹。

Now moving to the next slide on Slide 14. Just a few words on some of the data readouts. Ianalumab is active, we're very excited about. This is our anti-BAFF receptor monoclonal antibody. Had very strong data in Sjögren's syndrome in a Phase IIb study. We'll be moving into Sjögren's Phase III later this year. We are all planning as well shortly to initiate studies in Phase III for lupus nephritis. We're advancing in SLE as well as in autoimmune hepatitis and expect additional data over the coming 12 months on these 2 indications. And we're also looking to progress within B-cell malignancies, where we believe an anti-BAFF receptor antibody could provide an additional option for these patients. Taken together, we think this asset has the potential to be the "pipeline" in a single asset. And we look forward to advancing it across a broad range of indications.

現在轉到幻燈片 14 的下一張幻燈片。簡單介紹一些數據讀數。 Ianalumab 很活躍，我們對此感到非常興奮。這是我們的抗 BAFF 受體單克隆抗體。在 IIb 期研究中獲得了非常有力的干燥綜合徵數據。我們將在今年晚些時候進入 Sjögren 的第三階段。我們都計劃在短期內啟動狼瘡腎炎的 III 期研究。我們正在 SLE 和自身免疫性肝炎方面取得進展，並期望在未來 12 個月內獲得關於這兩個適應症的更多數據。我們還希望在 B 細胞惡性腫瘤方面取得進展，我們相信抗 BAFF 受體抗體可以為這些患者提供額外的選擇。綜上所述，我們認為該資產有可能成為單一資產中的“管道”。我們期待著在廣泛的適應症中推進它。

I already mentioned the Cosentyx data in HS. This is a high unmet need area. Hidradenitis suppurativa is a severe, debilitating condition. A good efficacy profile, a strong safety profile. We are keeping the study blinded until the 52-week time point. And following that 52-week safety data, we will then be able to move forward with submissions in the U.S. Submissions in the EU are already under preparation, and we would expect them in the first half.

我已經提到了 HS 中的 Cosentyx 數據。這是一個高度未滿足的需求領域。化膿性汗腺炎是一種嚴重的、使人衰弱的疾病。良好的功效概況，強大的安全性概況。我們將這項研究保持盲態，直到 52 週的時間點。在獲得 52 週的安全數據之後，我們將能夠繼續在美國提交申請。在歐盟提交的申請已經在準備中，我們預計會在上半年提交。

And as I mentioned with ligelizumab, data demonstrated superiority versus placebo, but not superiority versus Xolair. And we'll provide a further update on this asset in terms of its progress in CSU shortly. However, we do believe there's potential for the medicine in food allergy and CIndU, given there is no approved anti-IgE therapy -- [IzE therapy] in this indication.

正如我在使用 ligelizumab 時提到的那樣，數據證明了與安慰劑相比的優勢，但與 Xolair 相比沒有優勢。我們將在不久後就其在 CSU 中的進展提供有關該資產的進一步更新。然而，我們確實相信該藥物在食物過敏和 CIndU 方面具有潛力，因為沒有批准的抗 IgE 療法 - [IzE 療法] 在該適應症中。

Now moving to Slide 15. Just to say a word about the data we recently presented in December. On our T-Charge platform, our next-generation CAR-T platform, which we're excited about, given the potential to provide [rapid] access to therapy, hopefully improved rates of response and longer durability as well as attractive economics in terms of its production and scalability.

現在轉到幻燈片 15。就我們最近在 12 月提供的數據說一下。在我們的 T-Charge 平台上，我們感到興奮的是我們的下一代 CAR-T 平台，因為它有可能提供[快速] 治療，有望提高反應率和更長的耐用性以及有吸引力的經濟性其生產和可擴展性。

YTB, which is indicated for DLBCL, in a small study of 16 patients, demonstrated a 73% CR rate at month 3. And we're looking forward now to reading out the 6-month data over the coming months. And we plan to start a Phase III trial in DLBCL this summer for this asset. And PHE in multiple myeloma, the BCMA-directed CAR-T. Again, early data, but in the first 6 patients, 100% ORR.

YTB 用於 DLBCL，在一項針對 16 名患者的小型研究中，在第 3 個月顯示 73% 的 CR 率。我們現在期待在未來幾個月內讀出 6 個月的數據。我們計劃今年夏天在 DLBCL 開始一項針對這項資產的 III 期試驗。和多發性骨髓瘤中的 PHE，BCMA 指導的 CAR-T。同樣，早期數據，但在前 6 名患者中，ORR 為 100%。

And what's unique about this technology platform is its ability to preserve what's termed as T cell stemness, the ability of T cells to regenerate themselves to hopefully lead to more long and durable responses if a cancer occurrence should occur. Also, it enables a shortened time frame for cells to be out of the patient's body.

該技術平台的獨特之處在於它能夠保持所謂的 T 細胞乾性，即 T 細胞自我再生的能力，如果發生癌症，有望產生更持久的反應。此外，它還可以縮短細胞離開患者身體的時間。

So many things to be excited about. Early days, but we look forward to taking this forward, and hopefully, over time, bringing additional targets onto the T-Charge platform.

有這麼多令人興奮的事情。早期，但我們期待著將其向前推進，並希望隨著時間的推移，將更多目標帶到 T-Charge 平台上。

Then moving to Slide 16. In the quarter as well, we signed 4 additional BD&L deals to strengthen the pipeline. We acquired Gyroscope, which has a onetime subretinal, a Phase II gene therapy, that have the potential to transform the care of geographic atrophy. In early data in 9 patients, rather remarkable results that we saw for this onetime administration. We'll now have to see how those results hold up in larger Phase II studies. But at least the potential to address a very large market and a very large patient unmet need with a onetime therapy.

然後轉到幻燈片 16。在本季度，我們還簽署了 4 項額外的 BD&L 交易以加強管道。我們收購了 Gyroscope，它具有一次性的視網膜下、II 期基因療法，有可能改變地理萎縮的護理。在 9 名患者的早期數據中，我們看到了這一一次性給藥的相當顯著的結果。我們現在必須看看這些結果如何在更大的 II 期研究中成立。但至少有潛力通過一次性治療解決一個非常大的市場和一個非常大的患者未滿足的需求。

We signed an option agreement with BeiGene for ociperlimab, the Phase III TIGIT inhibitor, currently being run by BeiGene in global Phase III studies in solid tumors, particularly in lung cancer, EFCC and cervical cancer. We are looking forward to working with BeiGene to fully build out this program over the course of the year; and then as data continues to materialize, determine if a full opt-in would be warranted.

我們與百濟神州簽署了一項關於 ocperlimab 的期權協議，該 III 期 TIGIT 抑製劑目前由百濟神州在實體瘤的全球 III 期研究中運營，特別是在肺癌、EFCC 和宮頸癌方面。我們期待與百濟神州合作，在這一年裡全面建設這個項目；然後隨著數據的不斷具體化，確定是否需要完全選擇加入。

We signed our opt-in agreement with Molecular Partners for ensovibep, which has the potential to be a broad-spectrum coronavirus therapeutic for patients in the outpatient setting. It has 3 -- target is the spike protein in 3 separate binding domains, opportunity for bacterial production. So much higher yields and a much more efficient production, also higher scales. We are on track in our discussions with the FDA to complete an emergency use authorization filing. And then it would be determined by a review matter if the FDA would ultimately provide an approval. We also continue to be in discussions with the U.S. government as well as other governments around the world regarding this therapeutic as well as advancing the Phase III trial and subcutaneous formulation.

我們與 Molecular Partners 簽署了 ensovibep 的選擇加入協議，該協議有可能成為門診患者的廣譜冠狀病毒治療藥物。它有 3 - 目標是 3 個單獨的結合域中的刺突蛋白，細菌生產的機會。更高的產量和更高效的生產，以及更高的規模。我們正在與 FDA 討論完成緊急使用授權備案。然後，如果 FDA 最終提供批准，將由審查事項決定。我們還將繼續與美國政府以及世界其他政府就該療法以及推進 III 期試驗和皮下製劑進行討論。

And then lastly, we signed an agreement with UCB for the co-development and co-commercialization of an alpha-synuclein small molecule inhibitor, now an opportunity to tackle Parkinson's disease with a small molecule agent against, I think, a very exciting target. Early data, early days, but certainly, the potential to address a major unmet need.

最後，我們與 UCB 簽署了一項共同開發和共同商業化 α-突觸核蛋白小分子抑製劑的協議，現在這是一個用小分子藥物治療帕金森病的機會，我認為這是一個非常令人興奮的目標。早期數據，早期數據，但肯定是解決主要未滿足需求的潛力。

Now turning to Slide 17. Slide 17 and the following slide as well give you an overview, one kind of a snapshot of our portfolio in pharmaceuticals. In cardio-renal, things are on track, and you can see some additional progress we've made on the Leqvio outcome studies. And iptacopan and pelacarsen also remain on track. In neuroscience, Zolgensma, we've initiated the Phase III intrathecal study now. Branaplam has also now initiated in its Phase IIb study of Huntington's disease. I already mentioned remibrutinib and our agent in Parkinson's disease. And across the immunology portfolio, a number of ongoing projects and programs in Phase II and Phase III all largely on track. At the bottom, you see the status of our wild card programs. Later this year, we would have readouts for QBW and UNR. And we continue to also progress the other agents in that box as well.

現在轉到幻燈片 17。幻燈片 17 和下面的幻燈片也為您提供了概述，這是我們在製藥領域的投資組合的一種快照。在心腎領域，事情正在走上正軌，您可以看到我們在 Leqvio 結果研究方面取得的一些額外進展。 iptacopan 和 pelacarsen 也保持在正軌上。在神經科學領域，Zolgensma，我們現在已經啟動了 III 期鞘內研究。 Branaplam 現在也開始了亨廷頓病的 IIb 期研究。我已經提到了瑞布替尼和我們治療帕金森病的藥物。在整個免疫學組合中，許多正在進行的 II 期和 III 期項目和計劃都基本步入正軌。在底部，您可以看到我們的通配符計劃的狀態。今年晚些時候，我們將獲得 QBW 和 UNR 的讀數。我們還將繼續改進該框中的其他代理。

Then turning to Slide 18. In oncology, we also are progressing on track in solid tumors and hematology. The Kisqali NATALEE readout is on track for -- it's an event-driven readout, but we continue to expect it by the end of 2022. If the event rate changes and it slips into '23, we'll of course let the markets know. The CANOPY-A study also is on track for a readout in the second half of this year.

然後轉到幻燈片 18。在腫瘤學方面，我們也在實體瘤和血液學方面取得進展。 Kisqali NATALEE 讀數正按計劃進行——它是一個事件驅動的讀數，但我們仍預計到 2022 年底它會出現。如果事件發生率發生變化並滑入 23 年，我們當然會讓市場知道. CANOPY-A 研究也有望在今年下半年公佈。

Lu-PSMA, Importantly, the additional readout for our PSMAfore study, again, an event-driven study, but we're hopeful to have a readout on that in the earlier lines of prostate cancer by the end of 2022. And the review of Lu-PSMA with the FDA is on track, given its action date later this quarter. And we also progressed JDQ with TNO. We look forward to presenting additional data on the combination, we hope, over the coming 12 months.

Lu-PSMA，重要的是，我們的 PSMAfore 研究的額外讀數，再次，一個事件驅動的研究，但我們希望在 2022 年底之前在前列腺癌的早期線中獲得讀數。鑑於本季度晚些時候的行動日期，與 FDA 合作的 Lu-PSMA 正步入正軌。我們還與 TNO 一起推進了 JDQ。我們期待在未來 12 個月內提供有關該組合的更多數據。

In hematology, the asciminib first-line approval. Third-line approval we've already achieved, and Susanne will speak more about that. And then I've already mentioned some of the other agents here. Sabatolimab, our anti-TIM-3, on track for a PFS readout in the first half of this year. And the various other studies moving towards PFS and OS will come over the coming year as well. So a lot going on.

在血液學方面，阿西米尼一線獲批。我們已經獲得了三線批准，Susanne 將對此進行更多說明。然後我已經在這裡提到了其他一些代理。我們的抗 TIM-3 Sabatolimab 有望在今年上半年進行 PFS 讀數。其他各種轉向 PFS 和 OS 的研究也將在來年進行。所以發生了很多事情。

We expect additional readouts, particularly in the back half of this year and heading into 2023. When you look at Slide 19, you can see the full list of expected events, regulatory decisions, submissions, submission-enabling readouts, additional readouts. And you can also see a large number of pivotal study starts. These studies will be important for us to continue to advance the 20-plus assets that we've been talking about that will drive growth in 2025 and beyond.

我們預計會有更多的讀數，特別是在今年下半年和 2023 年。當您查看幻燈片 19 時，您可以看到預期事件、監管決定、提交、支持提交的讀數、額外讀數的完整列表。而且你還可以看到大量的關鍵研究開始。這些研究對於我們繼續推進我們一直在談論的 20 多種資產將非常重要，這將推動 2025 年及以後的增長。

So moving to Slide 20. Just to say also a word on Sandoz. We saw Sandoz stabilizing in quarter 4. You saw sales growth plus 2% in the quarter as well as biopharma growing 7% in constant currencies. When we think about the outlook for 2022, we forecast sales to be broadly in line. And Harry will talk a little bit more about the specifics on the guidance. We're assuming here that cough and cold reverts to pre-COVID levels, that biosimilars continues to perform, particularly in Europe, where we have a very strong market position. But we also face continued gross margin headwinds due to the price erosion and unfavorable mix, particularly in the U.S., which we expect to fully bottom out in this year and start to move towards a growth dynamic in the back half of next year.

所以轉到第 20 張幻燈片。順便說一下 Sandoz。我們看到山德士在第 4 季度企穩。您看到本季度銷售額增長 2%，生物製藥增長 7%（按固定匯率計算）。當我們考慮 2022 年的前景時，我們預計銷售額將大致符合預期。哈利將更多地談論指導的細節。我們在這裡假設咳嗽和感冒恢復到 COVID 之前的水平，生物仿製藥繼續發揮作用，特別是在我們擁有非常強大的市場地位的歐洲。但由於價格侵蝕和不利的組合，我們也面臨持續的毛利率逆風，尤其是在美國，我們預計今年將完全觸底並在明年下半年開始走向增長動力。

Our biosimilars launches however continue to be on track. And we're expecting these launches to drive material growth in the back half of 2023, into 2024 and beyond. There are $80 billion of originator sales, a large opportunity. We have 15-plus assets somewhere in development. So that will be absolutely critical to move Sandoz into a strong growth dynamic looking ahead.

然而，我們的生物仿製藥的推出繼續走上正軌。我們預計這些發布將推動 2023 年下半年、2024 年及以後的物質增長。有 800 億美元的原創銷售額，這是一個巨大的機會。我們有 15 多種資產正在開發中。因此，這對於使山德士在未來實現強勁增長動力至關重要。

Moving to Slide 21. A word on our capital allocation strategy. We remain disciplined and shareholder-focused and really trying to balance the 4 elements of our strategy. And this is a shift. We're not ranking them, but rather really showing them as a balanced approach. We invest in our organic business. You can see $9 billion in R&D, over $1 billion in capital investments. We also continue to look at value-creating bolt-ons. We've done around $30 billion of acquisitions since 2018. And we also returned value to shareholders through our annual dividend, where we propose this year to increase by 3% Swiss francs and 6% in U.S. dollars. And as announced in the quarter 4, we continue to also return our capital to shareholders where appropriate. Share buybacks of $2.8 billion were executed in 2021, and we're on track with respect to the $15 billion share buyback program that we announced in the back half of last year, which we expect, given the nature of the Swiss second line -- second trading line cancellations, take us until the end of 2023 to fully complete.

轉到幻燈片 21。關於我們的資本配置策略。我們保持紀律嚴明，以股東為中心，並真正努力平衡我們戰略的四個要素。這是一個轉變。我們沒有對它們進行排名，而是真正將它們展示為一種平衡的方法。我們投資於我們的有機業務。你可以看到 90 億美元的研發，超過 10 億美元的資本投資。我們還繼續關注創造價值的附加組件。自 2018 年以來，我們已經完成了大約 300 億美元的收購。我們還通過年度股息向股東回報價值，我們建議今年增加 3% 的瑞士法郎和 6% 的美元。正如第 4 季度所宣布的那樣，我們還將繼續在適當的情況下將資本返還給股東。 2021 年執行了 28 億美元的股票回購，鑑於瑞士二線的性質，我們預計去年下半年宣布的 150 億美元股票回購計劃正在步入正軌——第二條交易線取消，要到2023年底才能完全完成。

So moving to Slide 22. From an ESG standpoint, we continue to make important progress in Sub-Saharan Africa with respect to our human rights commitments, in terms of disability inclusion. Our environmental targets are on track with 34% Scope 1 and 2 reductions, excluding offset waste disposal, also reduce and on track to be at half by 2025, all on track towards our goal of being carbon neutral across Scopes 1 through 3 by 2030 and fully net 0 by 2040. And sooner -- as soon as possible is our aspiration. And this has all led to improved scores from an MSCI. We are no longer having an MSCI controversy red flag, ranked #2 in the Access to Medicine Index and also favorably ranked in the S&P Global ESG Ratings, amongst other ratings that we've had over the course of the year.

所以轉到幻燈片 22。從 ESG 的角度來看，我們繼續在撒哈拉以南非洲地區在殘疾包容方面的人權承諾方面取得重要進展。我們的環境目標步入正軌，範圍 1 和範圍 2 減少 34%，不包括抵消性廢物處理，也將減少並有望在 2025 年減半，所有這些都朝著我們到 2030 年在範圍 1 至範圍 3 中實現碳中和的目標邁進到 2040 年完全淨 0。而且越快——越快是我們的願望。這一切都導致MSCI的分數提高。我們不再有 MSCI 爭議紅旗，在 Access to Medicine Index 中排名第二，在 S&P 全球 ESG 評級中也處於有利地位，以及我們在這一年中獲得的其他評級。

So in closing on Slide 23. Just wanted to highlight the priorities for the company over the course of the year. The successful launches of Leqvio, Kesimpta, Lu-PSMA, which we believe has the potential to be a very significant asset, and Scemblix, where, again, we have the opportunity to build on a third-line approval and hopefully move into earlier lines of therapy. Maintain the growth momentum on our 6 multibillion-dollar assets that are the assets that we believe will drive the company's base level of growth over the coming years; progressing the pipeline of 20-plus potential significant sales assets, with the opportunity that be approved by 2026; optimize our portfolio with the Sandoz review, with a plan to have this updated by the end of 2022; and remain disciplined and thoughtful on our BD and M&A to build the growth profile of the company, but also ensure attractive returns for our shareholders; deliver those returns through our productivity initiatives, especially in manufacturing and business services, as we move towards the high 30s in our margins as well as an attractive return on invested capital profile; and continue to reinforce the foundations of a great company, a strong culture that drives performance, leadership in data science to drive value across the business and being an ESG leader.

因此，在幻燈片 23 結束時。只想強調公司在這一年中的優先事項。 Leqvio、Kesimpta、Lu-PSMA 的成功推出，我們認為這有可能成為一項非常重要的資產，以及 Scemblix，我們再次有機會在三線批准的基礎上進行開發，並有望進入更早的生產線的治療。保持我們數十億美元資產的增長勢頭，我們認為這些資產將推動公司未來幾年的基本增長水平；推進 20 多項潛在重大銷售資產的管道建設，有機會在 2026 年之前獲得批准；通過 Sandoz 審查優化我們的產品組合，併計劃在 2022 年底之前對其進行更新；在我們的業務拓展和併購方面保持紀律和深思熟慮，以建立公司的增長形象，同時確保我們的股東獲得可觀的回報；通過我們的生產力計劃提供這些回報，特別是在製造和商業服務方面，因為我們的利潤率邁向了 30 多歲的高位，投資資本狀況也獲得了有吸引力的回報；並繼續鞏固一家偉大公司的基礎、推動業績的強大文化、推動整個業務價值的數據科學領導力以及成為 ESG 領導者。

So thank you very much. And with that, I'll hand it over to Marie-France.

所以非常感謝。有了這個，我會把它交給 Marie-France。

Good morning, good afternoon to all. On Slide 25, I'm pleased to share the quarter 4 results of the Pharma division with you. Our sales grew 9% this quarter. As you know, we're fully focused on our growth drivers and launches and the rejuvenation of our portfolio. You can expect us to continue to drive this shift in 2022 and beyond.

早上好，大家下午好。在幻燈片 25 上，我很高興與您分享製藥部門第四季度的業績。本季度我們的銷售額增長了 9%。如您所知，我們完全專注於我們的增長動力和發布以及我們產品組合的複興。您可以期待我們在 2022 年及以後繼續推動這一轉變。

So moving on to Slide 26. Cosentyx delivered $1.2 billion in revenues and grew 13% in the quarter. We've seen strong demand for Cosentyx across geographies. We did see some impact in China due to the year-end budget caps. However, we've already seen a strong rebound in Q1. Our life cycle program is starting to deliver, with the positive readout for hidradenitis suppurativa and IV and will start to be a growth driver in 2023.

所以繼續幻燈片 26。Cosentyx 實現了 12 億美元的收入，本季度增長了 13%。我們已經看到各個地區對 Cosentyx 的強勁需求。由於年終預算上限，我們確實在中國看到了一些影響。然而，我們已經看到第一季度的強勁反彈。我們的生命週期計劃開始交付，化膿性汗腺炎和 IV 的讀數呈陽性，並將在 2023 年開始成為增長動力。

If we look to 2022, our focus is on volume growth in all geographies, especially China. In the U.S., our access position is stable and we plan to grow with the market. As we will not benefit from the price favorability we saw last year, volume growth for us is key. You can expect to see the typical quarter-over-quarter decline in Q1, followed by continued double-digit growth for the full year, fully on track to deliver on our $7 billion plus guidance.

如果我們展望 2022 年，我們的重點是所有地區的銷量增長，尤其是中國。在美國，我們的准入地位穩定，我們計劃與市場一起成長。由於我們不會從去年看到的價格優惠中受益，因此銷量增長對我們來說是關鍵。您可以期望看到第一季度典型的季度環比下降，隨後全年繼續保持兩位數增長，完全有望實現我們超過 70 億美元的指導。

If I move on to Slide 27. Entresto grew 34% in the quarter, finishing the year at $3.5 billion in sales. We continue to pull through the first-line recommendations in the U.S. and Europe. And we continue to have good traction with the expanded label in the U.S., which, as you know, includes 5 out of 6 patients with heart failure.

如果我繼續看幻燈片 27。Entresto 在本季度增長了 34%，全年銷售額為 35 億美元。我們繼續採納美國和歐洲的一線建議。我們繼續在美國擴大標籤的吸引力，如您所知，其中包括 6 名心力衰竭患者中的 5 名。

In China, we renewed our NRDL listing for heart failure, and we are thrilled that hypertension is now listed. The dip that you see in the ex U.S. sales column is for China, and that is because of the wholesaler compensation for stock given our new price. But again, this is on the back of very good news. Now that we have the listing, we also have access to a much broader population. And if you think about the fact that only 15% of patients in China -- or hypertensive patients in China are well controlled versus, for example, 52% in the U.S., you can start to see the potential.

在中國，我們更新了心力衰竭國家醫保目錄，我們很高興高血壓現在被列入名單。您在前美國銷售欄中看到的下降是針對中國的，這是因為批發商根據我們的新價格對庫存進行補償。但同樣，這是非常好消息的背後。現在我們有了列表，我們也可以接觸到更廣泛的人群。如果你想想中國祇有 15% 的患者——或者說中國的高血壓患者得到了很好的控制，而美國的這一比例為 52%，你就會開始看到潛力。

For 2022, we are absolutely confident we can maintain Entresto's momentum in the U.S., in Europe, driving broader and earlier adoption, but we're also very excited about our opportunities in Asia.

對於 2022 年，我們絕對有信心保持 Entresto 在美國和歐洲的發展勢頭，推動更廣泛和更早的採用，但我們也對我們在亞洲的機會感到非常興奮。

If I move on to Slide 28. We're now in our third year in the marketplace with Zolgensma, and we've treated 1,800 babies. Because this is a onetime therapy, you will continue to see volatility in the quarters as new markets gain access, as we add the bolus and then move on to an incident population. Our focus is clear. We want to maintain a leading position in the U.S., focusing on the infant population. We want to accelerate newborn screening. We know it's really important to treat SMA as early as possible. And therefore, our plan is to double the rate of newborn screening in Europe. And three, we want to continue on our plan for geographic expansion into emerging markets.

如果我繼續看幻燈片 28。我們現在是 Zolgensma 進入市場的第三個年頭，我們已經治療了 1,800 名嬰兒。因為這是一次性治療，隨著新市場的進入，您將繼續看到季度波動，因為我們添加了推注，然後轉移到事件人群。我們的重點很明確。我們希望保持在美國的領先地位，專注於嬰兒人群。我們希望加快新生兒篩查。我們知道儘早治療 SMA 非常重要。因此，我們的計劃是將歐洲的新生兒篩查率提高一倍。第三，我們希望繼續我們在新興市場的地域擴張計劃。

In parallel, we're progressing with our IT formulation. We're laying the foundation to bring Zolgensma to patients across the full SMA spectrum. Our STEER study has just opened and just recruited its first patient. And we're also conducting a study in pretreated patients who may benefit from Zolgensma's onetime treatment.

與此同時，我們正在推進我們的 IT 制定。我們正在為將 Zolgensma 帶給整個 SMA 譜系的患者奠定基礎。我們的 STEER 研究剛剛開始並招募了第一位患者。我們還在對可能從 Zolgensma 的一次性治療中受益的預治療患者進行研究。

If I move on to Slide 29. With Kesimpta, we finished the year strong with $147 million sales in Q4. We maintain a high share of voice. We now reach a critical mass with multiple sclerosis specialists. We continue to onboard new patients, and the majority of those patients continue to be in first line, first switch. There is no question that B-cell therapy is now the gold standard in efficacy.

如果我繼續幻燈片 29。有了 Kesimpta，我們在第四季度以 1.47 億美元的銷售額完成了強勁的一年。我們保持較高的發言權。我們現在與多發性硬化症專家達成了臨界質量。我們繼續接收新患者，其中大多數患者繼續處於第一線，首先轉換。毫無疑問，B 細胞療法現在是療效的金標準。

We also know that there have been questions on safety in context of COVID. And this has been a priority for us, to provide relevant answers to our customers. With the reassuring vaccination data that we have, we are building additional confidence in Kesimpta's profile and providing further important clinical differentiation in the marketplace. As we drive additional uptake in the U.S. and continue to execute on our launches across the world, you can expect us to continue to do everything to make this Kesimpta story even better.

我們也知道在 COVID 的背景下存在安全問題。這一直是我們的首要任務，為我們的客戶提供相關的答案。憑藉我們擁有的令人放心的疫苗接種數據，我們正在對 Kesimpta 的概況建立額外的信心，並在市場上提供進一步重要的臨床差異化。隨著我們在美國推動更多吸收並繼續在全球範圍內執行我們的發布，您可以期望我們繼續盡一切努力使 Kesimpta 的故事變得更好。

Moving on to Slide 30. As you know, we've received FDA approval in December for Leqvio, and we've been in the field for 2 weeks. On the system side, we are implementing our strategy. Our focus right now is to support the P&T reviews and the implementation of acquisition or referral processes. We started onboarding alternative injection centers, and we continue to broaden our network. We've also filed for a permanent J-Code as we planned.

繼續幻燈片 30。如您所知，我們在 12 月獲得了 FDA 對 Leqvio 的批准，我們已經在該領域工作了 2 週。在系統方面，我們正在實施我們的戰略。我們現在的重點是支持 P&T 審查和收購或推薦流程的實施。我們開始加入替代注射中心，並繼續擴大我們的網絡。我們還按計劃申請了永久 J-Code。

On the health care professional side, we're educating on Leqvio's clinical profile, the twice-yearly dosing and the breadth of the label. We are really excited about the enthusiasm that we're getting from the market on the clinical aspects, but also seeing the high willingness of physicians to discuss the nonclinical support options. As was said before, the first half of the year will be about laying the foundation to drive the uptake in second half of the year and beyond, when some of the larger systems should be ready for buy and bill, and of course, when our permanent J-Code should be issued.

在醫療保健專業方面，我們正在對 Leqvio 的臨床概況、每年兩次的劑量和標籤的廣度進行教育。我們對市場對臨床方面的熱情感到非常興奮，同時也看到醫生討論非臨床支持選項的高度意願。如前所述，今年上半年將為推動下半年及以後的採用奠定基礎，屆時一些較大的系統應該準備好購買和開票，當然，當我們的應頒發永久 J 代碼。

On a separate note, we've also made significant progress with the NHS on the implementation plan and are awaiting the lift on the moratorium of all non-COVID-related communication and initiatives to begin the rollout of the agreement.

另外，我們還與 NHS 在實施計劃方面取得了重大進展，並正在等待取消所有與 COVID 無關的溝通和舉措，以開始推出該協議。

So in summary, on Slide 31. 2021 was a strong year for Pharma. I want to thank the teams for the focus, the bold thinking and the diligence around customer obsession and market metrics to deliver exquisite execution. You will see us continue to build on that strong foundation in 2022, with the right investments, not only in our products, but also in new partnerships, customer engagement and digital tools.

總而言之，在幻燈片 31 上。2021 年對 Pharma 來說是強勁的一年。我要感謝團隊的專注、大膽的思考和圍繞客戶痴迷和市場指標的勤奮，以提供出色的執行。您將看到我們在 2022 年繼續在這個堅實的基礎上再接再厲，進行正確的投資，不僅在我們的產品上，而且在新的合作夥伴關係、客戶參與和數字工具方面。

So thank you very much. And now let me pass it on to Susanne.

所以非常感謝。現在讓我把它轉給 Susanne。

Thank you, Marie-France. And moving to Oncology on Slide 33. You see that the Oncology business grew 4% in 2021, reaching $15.5 billion, with our growth drivers increasing 17% versus prior year. And also Q4 was a solid quarter, growing 3%. As you see, the growth was driven by continued double-digit growth of brands like Kisqali, Promacta/Revolade, Tafinlar + Mekinist and Jakavi. We are very pleased to see a continued strong portfolio rejuvenation, with these growth drivers now representing 54% of the total portfolio.

謝謝你，瑪麗-法蘭西。在幻燈片 33 上轉向腫瘤學。您會看到，腫瘤學業務在 2021 年增長了 4%，達到 155 億美元，我們的增長驅動力比去年增長了 17%。第四季度也是一個穩健的季度，增長了 3%。如您所見，增長是由 Kisqali、Promacta/Revolade、Tafinlar + Mekinist 和 Jakavi 等品牌的持續兩位數增長推動的。我們很高興看到投資組合持續強勁復甦，這些增長驅動因素現在佔總投資組合的 54%。

Moving to Slide 34: Kisqali. We saw a very strong performance, growth of 58% in Q4, reaching now $285 million in sales. We saw increased demand across all region as a reflection of further penetration in the first-line post-menopausal segment. We continue to gain share in the U.S., with NBRx in the metastatic setting reaching 17% in November '21. And in the international markets, we had an impressive growth of 90%, mostly driven by Europe, where we sustained leadership in premenopausal setting, but also increased penetration in the largest postmenopausal setting.

轉到幻燈片 34：Kisqali。我們看到了非常強勁的表現，第四季度增長了 58%，現在銷售額達到了 2.85 億美元。我們看到所有地區的需求增加，反映了一線絕經後細分市場的進一步滲透。我們繼續在美國獲得份額，21 年 11 月 NBRx 在轉移性環境中達到 17%。在國際市場上，我們實現了 90% 的驚人增長，主要是受歐洲推動，我們在絕經前環境中保持領先地位，但在最大的絕經後環境中的滲透率也有所提高。

With the MONALEESA-2 data presented at ESMO, Kisqali demonstrated the longest median overall survival so far in advanced breast cancer, and we now have OS data across all eligible patient populations. And this is why Kisqali is also the only CDK4/6 inhibitor highlighted in the U.S. NCCN guidelines to demonstrate OS benefit in first line. So we are moving forward with confidence in Kisqali. And in collaboration with the SOLTI study group, we have initiated the Phase III HARMONIA trial to evaluate Kisqali versus palbociclib in advanced breast cancer.

借助 ESMO 提供的 MONALEESA-2 數據，Kisqali 證明了迄今為止晚期乳腺癌中位總生存期最長的，我們現在擁有所有符合條件的患者群體的 OS 數據。這就是為什麼 Kisqali 也是美國 NCCN 指南中唯一強調在一線證明 OS 益處的 CDK4/6 抑製劑的原因。因此，我們對 Kisqali 充滿信心地向前邁進。我們與 SOLTI 研究小組合作，啟動了 III 期 HARMONIA 試驗，以評估 Kisqali 與 palbociclib 在晚期乳腺癌中的療效。

In addition, we continue our geographical expansion of Kisqali, with reimbursement achievement in Brazil and regulatory submission in China. As you know, our key development program is the NATALEE trial studying Kisqali in adjuvant setting for both high- and intermediate-risk patients. And this study is fully recruited. And as Vas mentioned, the readout is expected towards the end of 2022. So overall, we very pleased with the Kisqali performance and expect continued momentum.

此外，我們繼續擴大 Kisqali 的地域擴張，在巴西取得報銷，並在中國提交監管申請。如您所知，我們的關鍵開發計劃是 NATALEE 試驗，研究 Kisqali 在高危和中危患者的輔助環境中。而且這項研究是完全招募的。正如 Vas 所提到的，預計將在 2022 年底發布讀數。因此，總的來說，我們對 Kisqali 的表現非常滿意，並期待繼續保持勢頭。

On Slide 35, you see 3 of our blockbusters: Tafinlar + Mekinist, Promacta or Revolade and Jakavi. These brands continue to deliver double-digit growth, driven by strong demand across regions.

在幻燈片 35 上，您會看到我們的 3 部大片：Tafinlar + Mekinist、Promacta 或 Revolade 和 Jakavi。在各地區強勁需求的推動下，這些品牌繼續實現兩位數的增長。

Tafinlar + Mekinist was growing 14%, with strong contribution from Europe. And just to remind ourselves, this is the first and only targeted therapy to achieve both 5-year overall survival in metastatic as well as adjuvant. And Tafinlar + Mekinist continues to sustain leadership in metastatic melanoma as the most used worldwide targeted therapy in the setting. Moving forward, we expect growth will primarily come from adjuvant melanoma and non-small cell lung cancer indication as well as the increased uptake in China.

Tafinlar + Mekinist 增長了 14%，其中來自歐洲的強勁貢獻。提醒我們自己，這是第一個也是唯一一個在轉移性和輔助性治療中實現 5 年總生存期的靶向治療。 Tafinlar + Mekinist 繼續保持在轉移性黑色素瘤領域的領先地位，成為該領域最常用的全球靶向治療。展望未來，我們預計增長將主要來自輔助性黑色素瘤和非小細胞肺癌適應症以及中國市場的增加。

Also, Promacta/Revolade reached very strong growth with 12%. And we saw this growth across all regions with share gains supported by the sustained efficacy and oral administration convenience. And we expect continued growth in ITP and SAA.

此外，Promacta/Revolade 實現了非常強勁的增長，達到 12%。我們在所有地區都看到了這種增長，持續的療效和口服給藥的便利性支持了份額增長。我們預計 ITP 和 SAA 將繼續增長。

And finally, Jakavi, reaching a 12% growth. This growth was driven by earlier usage in myelofibrosis and polycythemia vera. And we continue with our geographical expansion on graft-versus-host disease launches, and we expect further uptake there as well.

最後，Jakavi 實現了 12% 的增長。這種增長是由早期在骨髓纖維化和真性紅細胞增多症中的使用推動的。我們繼續在移植物抗宿主病的推出方面進行地域擴張，我們預計也將進一步吸收那裡。

So moving to Slide 36. Last quarter, as Vas mentioned, we have launched Scemblix in the U.S. And this is a unique STAMP inhibitor with superior clinical profile in late line CML that could potentially change the standard of care. And you see that Scemblix has a very strong clinical profile with a twofold improvement in major molecular response and a 3x reduction and discontinuation due to adverse event.

所以轉到幻燈片 36。上個季度，正如 Vas 所提到的，我們已經在美國推出了 Scemblix。這是一種獨特的 STAMP 抑製劑，在晚期 CML 中具有卓越的臨床特徵，可能會改變護理標準。您會看到 Scemblix 具有非常強大的臨床特徵，主要分子反應提高了兩倍，並且由於不良事件而減少了 3 倍和停藥。

So looking at the patient potential for Scemblix, that views that approximately 25% to 30% of CML patients may be eligible within the approved Scemblix label. And this includes patients experienced resistance or intolerance with previously treated 2 or more TKIs as well as patients with the T315I. And as you know, we have started a first-line registrational trial with filing expected in the first half of 2025.

因此，從 Scemblix 的患者潛力來看，大約 25% 到 30% 的 CML 患者可能符合批准的 Scemblix 標籤的條件。這包括對先前治療過的 2 種或更多 TKI 以及使用 T315I 的患者出現抗藥性或不耐受性的患者。如您所知，我們已經開始了一線註冊試驗，預計在 2025 年上半年提交。

So leveraging decades of experience in CML, Scemblix is off to a solid start in the U.S., with leading share of voice already within the first months. And this is complemented by a robust digital footprint with over 20,000 users and nearly 60,000 patient website visits. We have over 50 patients enrolled in our patient assistant program and have above 150 patients included in our managed access program. Scemblix is also already included in the [NCNN] guidelines. So we are also pursuing global commercialization, and the approvals in Europe and Japan remain on track for 2021.

因此，憑藉在 CML 領域數十年的經驗，Scemblix 在美國取得了良好的開端，在最初的幾個月內就已經佔據了領先的份額。強大的數字足跡補充了這一點，擁有超過 20,000 名用戶和近 60,000 次患者網站訪問。我們有超過 50 名患者參加了我們的患者助理計劃，並且有超過 150 名患者包括在我們的管理訪問計劃中。 Scemblix 也已包含在 [NCNN] 指南中。因此，我們也在追求全球商業化，歐洲和日本的批准在 2021 年保持在軌道上。

Moving to Slide 37. With our radioligand therapy, lutetium-PSMA-617, we have another exciting launch upcoming. Lutetium-PSMA has the potential to address the high unmet need in advanced metastatic castration-resistant prostate cancer. And results of the Phase III VISION trial demonstrated improved radiographic PFS and overall survival.

轉到幻燈片 37。借助我們的放射性配體療法 lutetium-PSMA-617，我們即將推出另一個令人興奮的產品。 Lutetium-PSMA 有可能解決晚期轉移性去勢抵抗性前列腺癌的高未滿足需求。 III 期 VISION 試驗的結果表明，影像學 PFS 和總生存期有所改善。

On the commercial side, we are moving forward with launch preparations. We are targeting 435 treatment sites across U.S. and Europe. We are leveraging our Lutathera footprint combined with an incremental field force dedicated to prostate cancer. In the U.S., that field force is fully recruited and trained. And the same is true for Europe, where we start building that field force. We don't foresee any hospital capacity constraints for the launch in this VISION population.

在商業方面，我們正在推進發布準備工作。我們的目標是在美國和歐洲建立 435 個治療點。我們正在利用我們的 Lutathera 足跡與專用於前列腺癌的增量場力相結合。在美國，這支野戰部隊是完全招募和訓練的。歐洲也是如此，我們開始建立這支野戰部隊。我們預計在這個 VISION 人群中的啟動不會有任何醫院容量限制。

And on the development side, we currently have 2 ongoing Phase III studies in the pre-taxane in the hormone-sensitive setting, with the potential to significantly expand the eligible population by up to 4x.

在開發方面，我們目前在激素敏感環境中對紫杉烷前進行了 2 項正在進行的 III 期研究，有可能將符合條件的人群顯著擴大多達 4 倍。

So in conclusion, moving to Slide 38. I would like to conclude with 3 important messages. First, in 2021, we continued to see solid execution on growth brands and portfolio rejuvenation, with sales from our growth drivers increasing 70% versus prior year. With Kisqali, one of our key brands, we continued to gain share in the CDK4/6 class and we have strong OS data in metastatic setting. And we are looking forward to the NATALEE readout in adjuvant. And we keep our focus on launch execution with Scemblix and lutetium-PSMA preparation and advancing our next wave of assets.

總而言之，轉到幻燈片 38。我想以 3 條重要信息作為結尾。首先，在 2021 年，我們繼續看到增長品牌和產品組合年輕化的穩健執行，我們增長動力的銷售額比上年增長了 70%。憑藉我們的主要品牌之一 Kisqali，我們繼續在 CDK4/6 類別中獲得份額，並且我們在轉移環境中擁有強大的操作系統數據。我們期待著佐劑中的 NATALEE 讀數。我們繼續專注於 Scemblix 和镥-PSMA 準備的啟動執行，並推進我們的下一波資產。

And with that, I'm handing over to Harry.

有了這個，我將交給哈利。

Yes. Thank you very much, Susanne. Good morning and good afternoon, everybody. So I'm now going to walk you through some of the financials for the fourth quarter and the full year as well as provide you with our 2022 guidance. As always, my comments refer to growth rates in constant currencies unless I would note it otherwise.

是的。非常感謝你，蘇珊。大家早上好，下午好。因此，我現在將向您介紹第四季度和全年的一些財務狀況，並為您提供我們的 2022 年指導。與往常一樣，除非我另有說明，否則我的評論指的是不變貨幣的增長率。

Turning to Slide 40. Here, we compare briefly our results with our latest 2021 guidance. As you can see, overall, our full year results were in line with guidance, with a particularly strong Innovative Medicines performance. Innovative Medicines grew the top line by 6%, and the bottom line, even double-digit by 10%. We are pleased that despite a challenging business environment during the year, we were able to deliver on our expectations.

轉到幻燈片 40。在這裡，我們將我們的結果與我們最新的 2021 年指南進行了簡要比較。如您所見，總體而言，我們的全年業績符合指引，創新藥物表現尤為強勁。創新藥物的收入增長了 6%，利潤增長了 10%，甚至達到了兩位數。我們很高興，儘管年內業務環境充滿挑戰，但我們仍能達到我們的預期。

Next slide, please. We finished the year on a strong quarter, with sales and core operating income growing 6% and 12%, respectively. This resulted in full year performance of 4% and 6% growth in top and bottom line. Net income of $24 billion benefited, of course, from the onetime gain from the Roche stake divestment of $14.6 billion. But even if you exclude that effect, and you see that in the lower line below net income, net income grew a healthy 15%, mainly due to higher sales and productivity gains.

請下一張幻燈片。我們以強勁的季度結束了這一年，銷售額和核心營業收入分別增長了 6% 和 12%。這導致全年業績增長 4% 和 6% 的頂線和底線。當然，240 億美元的淨收入受益於羅氏剝離股份的 146 億美元的一次性收益。但即使你排除了這種影響，你會看到在淨收入下方的下一行，淨收入增長了 15%，這主要是由於更高的銷售額和生產力的提高。

Core EPS grew 7%, mainly from a strong core operating income growth, and was slightly impacted by the Roche divestment in quarter 4. Free cash flow was up 14%, reaching $13.3 billion. And I will go a bit into more details about free cash flow a little later. Before we move on, just wanted to highlight that quarter 4 sales growth includes a positive 1 percent point impact from a small reclassification effect of contract manufacturing from other revenues to sales.

核心每股收益增長 7%，主要來自強勁的核心營業收入增長，並受到第四季度羅氏撤資的輕微影響。自由現金流增長 14%，達到 133 億美元。稍後我將詳細介紹自由現金流。在我們繼續之前，只是想強調第四季度的銷售增長包括來自合同製造從其他收入到銷售的小規模重新分類效應帶來的 1% 的積極影響。

Slide 42, please. This slide shows you the performance by division for the quarter and full year. Clearly, innovative Medicines had a strong year, driven by our key growth drivers, Entresto, Cosentyx, Zolgensma and the key oncology brands which also Marie-France and Susanne laid out. The Innovative Medicine sales grew 6%, bottom line, 10%. And margins reaching 36.2% points, up from 32% in 2018, so an increase over the 3-year period of 420 basis points. For the quarter, Innovative Medicines sales grew 7% and core operating income 15%.

請幻燈片 42。這張幻燈片向您展示了按部門劃分的季度和全年業績。顯然，在我們的主要增長驅動力 Entresto、Cosentyx、Zolgensma 以及 Marie-France 和 Susanne 佈局的主要腫瘤品牌的推動下，創新藥物今年表現強勁。創新藥物銷售額增長 6%，底線增長 10%。利潤率達到 36.2%，高於 2018 年的 32%，因此在 3 年期間增加了 420 個基點。本季度，創新藥物銷售額增長 7%，核心營業收入增長 15%。

As Vas mentioned, Sandoz is still facing some challenges, mainly from pricing pressures, especially in the U.S., and COVID-related demand impacts. Although quarter 4 showed signs of stabilization.

正如 Vas 所提到的，山德士仍面臨一些挑戰，主要來自定價壓力，尤其是在美國，以及與 COVID 相關的需求影響。儘管第 4 季度顯示出企穩跡象。

Now let's turn to Slide 43. Free cash flow of the year was mainly driven by the higher operating income and was up 14% to $13.3 billion. There were also lower payments from legal matters in 2021 compared to what we had in 2020. This was offset, as you can see, by the upfront payment for in-licensing of tislelizumab from BeiGene.

現在讓我們轉到幻燈片 43。今年的自由現金流主要受較高的營業收入推動，增長 14% 至 133 億美元。與 2020 年相比，2021 年的法律事務付款也較低。如您所見，這被百濟神州的 tislelizumab 許可預付款所抵消。

On the next slide, I'm very pleased to announce that we will propose our 25th consecutive dividend increase to CHF 3.10 per share from CHF 3 last year. This is an increase of 3.3% in Swiss franc and 6% in U.S. dollars, with our dividend reaching 4%. And fully aligned with our dividend policy of dividend increases every year in Swiss francs.

在下一張幻燈片上，我很高興地宣布，我們將提議連續第 25 次將股息從去年的 3 瑞士法郎增加到每股 3.10 瑞士法郎。瑞士法郎增長 3.3%，美元增長 6%，我們的股息達到 4%。並且完全符合我們每年以瑞士法郎增加股息的股息政策。

Now turning to Slide 45, where we sum up our guidance on top and bottom line. With the divisions, we expect another year of Innovative Medicine sales growing mid-single digits and core operating income to grow mid- to high single digits ahead of sales. The expected Innovative Medicines core margin increase will be driven by the expected good top line momentum and continuation of our productivity programs.

現在轉到幻燈片 45，我們在其中總結了我們對頂線和底線的指導。有了這些部門，我們預計創新藥物銷售額將再增長一年中個位數，核心營業收入將在銷售額之前增長中高個位數。預期的創新藥物核心利潤率增長將受到預期良好的頂線勢頭和我們生產力計劃的延續的推動。

For Sandoz, we expect the top line to be broadly in line with prior year and core operating income to decline low to mid-single digit, mainly driven by gross margin pressures due to pricing and product mix. Also on the top line, it's also due to the fact that we do not expect many launches for Sandoz in 2022.

對於山德士，我們預計收入將與去年基本持平，核心營業收入將下降到中個位數，主要是由於定價和產品組合帶來的毛利率壓力。同樣重要的是，這也是由於我們預計 Sandoz 不會在 2022 年推出很多產品。

With respect to the entire group, we expect both the top and the bottom line to grow mid-single digit. The key assumption for this guidance, as you can see in the bottom box here, is that we are continuing to return to normal global health care systems, including prescription dynamics. And that no Sandostatin LAR generics would enter in the U.S. in 2022.

就整個集團而言，我們預計頂線和底線都將增長中個位數。正如您在此處底部框中所見，本指南的關鍵假設是我們將繼續恢復正常的全球醫療保健系統，包括處方動態。並且沒有 Sandostatin LAR 仿製藥將在 2022 年進入美國。

On Slide 46, I would like to add some perspective on other key financial elements of our expected core net income performance. As you can see, we expect core net financial results to be broadly in line versus 2021. And the 2022 core tax rate is expected to be in the range of 17% to 17.5%. This is higher than the 16% core tax range -- tax rate range we experienced over the last couple of years. However, as you can see, approximately 1 percent point of this increase is due to the mathematical impact of the Roche divestment. And there may also be a slight increase due to geographical profit mix changes, which we will monitor throughout the year.

在幻燈片 46 上，我想就我們預期的核心淨收入表現的其他關鍵財務要素添加一些觀點。如您所見，我們預計核心淨財務業績與 2021 年基本一致。預計 2022 年核心稅率將在 17% 至 17.5% 之間。這高於 16% 的核心稅率範圍——我們在過去幾年中經歷的稅率範圍。但是，如您所見，這一增長中約有 1% 是由於羅氏撤資的數學影響。由於地域利潤組合的變化，也可能會略有增加，我們將在全年進行監控。

Finally on Slide 47. For modeling purposes, we thought it would be very helpful to you to go into some details regarding the currency impact, especially given the recent appreciation of the U.S. dollar. As you saw in quarter 4, currency had a negative impact of 2% on net sales and a negative 3 percent point impact on core operating income. As the U.S. dollar further strengthened, this currency effect, of course, also impacted the sales of our key growth drivers ex U.S. in quarter 4.

最後在幻燈片 47 上。出於建模目的，我們認為深入了解有關貨幣影響的一些細節對您非常有幫助，特別是考慮到最近美元升值。正如您在第 4 季度看到的那樣，貨幣對淨銷售額產生了 2% 的負面影響，對核心營業收入產生了 3% 的負面影響。隨著美元進一步走強，這種貨幣效應當然也影響了我們在第四季度除美國以外的主要增長動力的銷售。

If late January rates prevail for the remainder of 2022, we would expect the full year impact of currencies on top line to be a negative 3 percent points, and on bottom line, negative 4 percent points. In quarter 1, the impact is a bit more pronounced, and sales would be negative 4, and on bottom line, negative 5 points. As currency rates are quite volatile, as we all know, we update this impact estimate every month on our website.

如果 1 月下旬的利率在 2022 年剩餘時間內占主導地位，我們預計全年貨幣對頂線的影響為負 3 個百分點，在底線上為負 4 個百分點。在第一季度，影響更加明顯，銷售額為負 4 分，底線為負 5 分。眾所周知，由於匯率波動很大，我們每個月都會在我們的網站上更新此影響估計值。

And with this, I will hand it over back to Vas.

有了這個，我會把它交還給 Vas。

Terrific. Thank you, Harry. So moving to Slide 49 and briefly in closing. In '21, we delivered on our goal of mid-single -- our guidance of mid-single-digit top line growth, margin expansion and strong free cash flow. We remain confident in our in-market growth drivers, 6 major brands that are performing well across geographies, supporting our confidence in our outlook of 4% plus sales CAGR to 2026. We've continued to deliver important innovation milestones across the portfolio. And we'll work over the coming 12 to 24 months to deliver important milestones on our 20-plus key assets. And we remain balanced in our capital allocation, continuing to invest in innovation, alongside returning capital to our shareholders.

了不起。謝謝你，哈利。所以轉到幻燈片 49 並簡要結束。在 21 年，我們實現了中單的目標——我們對中個位數收入增長、利潤率擴張和強勁自由現金流的指導。我們仍然對我們的市場增長動力充滿信心，6 個主要品牌在各個地區都表現良好，這支持了我們對 4% 以及到 2026 年銷售複合年增長率的前景充滿信心。我們繼續在整個產品組合中實現重要的創新里程碑。我們將在未來 12 到 24 個月內努力實現我們 20 多項關鍵資產的重要里程碑。我們在資本配置方面保持平衡，繼續投資於創新，同時向股東返還資本。

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

有了這個，接線員，我們可以打開問題線。 （操作員說明）謝謝。操作員？

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

（操作員說明）您今天的第一個問題來自美國銀行的 Graham Parry。

So just regarding the Sandoz review. Obviously, you're looking there, you're saying all options are still on the table despite there being some recent speculation, again, about there being some private equity interest. And when you're considering a sale versus spin versus keeping the business, how much consideration are you giving to what multiple do you think the market would value Sandoz at versus what an acquirer might view it at?

所以只是關於山德士的評論。顯然，您正在尋找那裡，您說儘管最近有一些關於存在一些私人股本權益的猜測，但所有選項仍在桌面上。當您考慮出售、轉產和保留業務時，您認為市場對山德士的估值與收購方可能對山德士的估值是多少倍？

And secondly, in the scenario of a sale, what uses of cash would you consider, given that you're already doing a large buyback? So would the intent there to be to return capital to investors? Or to put it back into the business through M&A and organic investment?

其次，在出售的情況下，鑑於您已經在進行大量回購，您會考慮現金的哪些用途？那麼是否有將資本返還給投資者的意圖？還是通過併購和有機投資將其重新投入業務？

Thanks, Graham, for the question. Let me start with where we are on the process. And I think as we guided at the end of last year, the first part of this year is really focused on carving out the financials for Sandoz, being clear on the perimeter, and then being able to provide potential counterparties with the relevant information for them to make concrete formal offers, whether those are private equity or other companies. Alongside that, evaluate the options for a potential spin of the business, and lastly, a potential retention of the business. We are going through the work right now of evaluating those different options. And I expect that to take us to the middle of this year. Before then, we can take the next steps and hopefully come to a decision in the second half of the year.

謝謝，格雷厄姆，這個問題。讓我從我們在這個過程中所處的位置開始。而且我認為，正如我們去年年底所指導的那樣，今年上半年的重點是為山德士制定財務狀況，明確邊界，然後能夠為潛在的交易對手提供相關信息提出具體的正式報價，無論是私募股權還是其他公司。除此之外，評估業務潛在發展的選項，最後，評估業務的潛在保留。我們現在正在評估這些不同的選項。我希望這能把我們帶到今年年中。在此之前，我們可以採取下一步行動，並希望在下半年做出決定。

In terms of considerations. We're of course always looking at a few things. One, how to make Sandoz as successful as possible with -- consistent with the aspiration for Sandoz to become the leading generics company in the world. Second, what is most value-creating and also tax-efficient for our shareholders. We, I think, have proven with the Alcon spin that we're able to think through those considerations in a way that is beneficial to the shareholders and really making sure we're thinking about these things in a shareholder-friendly way.

在考慮方面。當然，我們總是在關註一些事情。一，如何讓山德士盡可能成功——這與山德士成為世界領先的仿製藥公司的願望相一致。其次，對我們的股東來說，什麼是最能創造價值和節稅的。我認為，我們已經通過愛爾康的旋轉證明了我們能夠以對股東有利的方式來考慮這些考慮因素，並真正確保我們以對股東友好的方式來考慮這些事情。

And I think it's really premature for us to speculate, if there were a "sale," how we would use the cash. And I think we're still a long ways away from that point in time. And we would of course be able to determine that at that point in time. But we would stay consistent with the balanced capital allocation approach which I outlined earlier, thinking through investing in the business versus returning value to shareholders. So thanks for the question, Graham.

而且我認為現在推測我們將如何使用現金還為時過早。而且我認為我們距離那個時間點還有很長的路要走。我們當然能夠在那個時間點確定這一點。但我們將與我之前概述的平衡資本分配方法保持一致，考慮投資業務與向股東回報價值。所以謝謝你的問題，格雷厄姆。

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

您的下一個問題來自法國巴黎銀行的 Richard Parkes。

I've got a question on capital allocation. I remember on the last call, you mentioned that you were engaging with investors around the sort of balance of returning the capital from the Roche stake sale between sort of buybacks and M&A. And I just wondered how your thoughts on M&A and business development had evolved based on that feedback. I'm just wondering if more meaningful bolt-ons have moved up or down the priority list, based on that feedback.

我有一個關於資本分配的問題。我記得在最後一次電話會議上，你提到你正在與投資者就羅氏股份出售中的回購和併購之間的資金返還平衡進行接觸。我只是想知道您對併購和業務發展的想法是如何根據這些反饋而演變的。我只是想知道根據該反饋是否有更有意義的附加組件在優先級列表中上移或下移。

Yes, thank you. Thank you, Richard. So I think not much more to say on the feedback. I mean, what I can -- I think we can say is that we know that given the strong cash flow that we generate at Novartis, we have the ability to continue to do bolt-on acquisitions, like we've done in the past, when we find attractive assets that fit with our therapeutic area goals and our platform goals.

是的，謝謝。謝謝你，理查德。所以我認為關於反饋沒有太多可說的了。我的意思是，我能——我想我們可以說的是，我們知道，鑑於我們在諾華產生的強勁現金流，我們有能力繼續進行補強收購，就像我們過去所做的那樣，當我們找到符合我們治療領域目標和平台目標的有吸引力的資產時。

As we evaluated the situation over the course of December, it became clear that at this point in time, we could return significant capital to shareholders through the buyback, while maintaining the ability to also do attractive, accretive M&A if it should materialize.

當我們在 12 月份評估情況時，很明顯在這個時間點，我們可以通過回購將大量資本返還給股東，同時保持進行有吸引力的增值併購的能力，如果它實現的話。

So right now, our focus is, of course, first and foremost, in driving the business and then evaluating the various options that are out there over time. But of course, being very patient to ensure we only do deals where we're confident that we can generate significant returns for the company and also fit with our strategic priorities.

所以現在，我們的重點當然首先是推動業務發展，然後評估隨著時間的推移出現的各種選擇。但是，當然，要非常耐心地確保我們只做我們有信心可以為公司帶來可觀回報並且符合我們的戰略重點的交易。

So I would say there's nothing imminent. And we're going to continue to evaluate the options and watch how valuations move in the sector and then look for opportunity as they arise. We're quite happy to continue to do deals, like the 4 deals that we've done in quarter 4, that enabled us to acquire 4 mid-stage and/or late-stage assets. Did some various deal structures we think at attractive financial terms.

所以我會說沒有什麼迫在眉睫的事情。我們將繼續評估期權並觀察該行業的估值如何變化，然後在出現機會時尋找機會。我們很高興繼續進行交易，例如我們在第四季度完成的 4 筆交易，這使我們能夠獲得 4 項中期和/或後期資產。是否以有吸引力的財務條款進行了一些我們認為的各種交易結構。

Harry, anything else you want to add on that?

哈利，你還有什麼要補充的嗎？

No. I think one element to see, I think, also feedback on the $15 billion share buyback has been quite positive. And also, maybe some analysts and investors are not very familiar with the Swiss system, where we have to buy these on the second line for cancellation. And that takes then unto the middle to the second half of next year, so '23, unlike U.S. situations where you can do this quite quickly. So as we see then -- can monitor the market, we do as much as we can on this $15 billion share buyback as we go forward. So there's a little bit of time to continue to think about the different ways of capital allocation.

不。我認為，我認為還有一個因素是對 150 億美元股票回購的反饋非常積極。而且，也許一些分析師和投資者對瑞士系統不是很熟悉，我們必須在二線購買這些以取消。然後到明年下半年，所以'23，不像美國的情況，你可以很快地做到這一點。因此，正如我們當時看到的那樣——可以監控市場，我們會在接下來的 150 億美元股票回購中盡我們所能。所以還有一點時間來繼續思考不同的資本配置方式。

And then, of course, we have to see, as Vas mentioned, would there be a great opportunistic M&A opportunity here? And otherwise, as we laid out the capital allocation priorities, that's how we're going to allocate continuously our capital.

然後，當然，我們必須看到，正如 Vas 所提到的，這裡是否存在巨大的機會主義併購機會？否則，當我們制定資本分配優先事項時，這就是我們將如何持續分配我們的資本。

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

您的下一個問題來自瑞銀的 Laura Sutcliffe。

A question on Leqvio, please. You talked a lot about the hard work you've done in removing access and reimbursement hurdles in the U.S. But do you think you need any specific guideline inclusions or recommendations to start driving use there? And is there the possibility of sort of trying to protocolize this in any way in your centers of interest to get sales going?

請教一個關於 Leqvio 的問題。你談了很多關於你在美國消除訪問和報銷障礙方面所做的艱苦工作。但你認為你需要任何具體的指南內容或建議來開始在那裡駕駛嗎？是否有可能嘗試在您的興趣中心以任何方式將其協議化以促進銷售？

Yes. Thanks, Laura. Marie-France?

是的。謝謝，勞拉。瑪麗-法蘭西？

Yes. So the first thing I'd say is that LDL lowering is already widespread across the guidelines, and we already have Class 1A in Europe. So when you asked your question, the intent philosophically of us going or concentrating on the 200 systems of care is exactly that. It's around, how do you protocolize the use or the management of lipid lowering within the system?

是的。所以我要說的第一件事是降低低密度脂蛋白已經在整個指南中普遍存在，我們在歐洲已經有了 1A 級。所以當你問你的問題時，我們去或專注於 200 個護理系統的哲學意圖正是如此。問題是，您如何在系統內對降脂的使用或管理進行規範化？

So how that looks like concretely will probably depend system by system. But as you know, we've just launched a cooperation with the AHA, which is around -- it's not necessarily specific to Leqvio, but it is around how do you better monitor and control cholesterol lowering for patients. So the intent is there, it's about making sure that we can identify the care pathways and then also support the centers in how they can specifically identify patients who come in when their LDL is not at the level that it should be or not at goal.

因此，具體看起來如何可能取決於系統。但如您所知，我們剛剛與 AHA 展開了合作，這並不一定是 Leqvio 特有的，而是圍繞著如何更好地監測和控制患者的膽固醇降低。所以目的就在那裡，它是關於確保我們能夠確定護理途徑，然後還支持中心如何具體識別當他們的 LDL 未達到應有或未達到目標水平時進來的患者。

So you're absolutely right. That's the intent. That's the way we're looking at it. Locally, it's going to look very different, country by country, system by system, but that's the goal. And ultimately, we'll change the landscape in ASCVD, because today, even though there are medicines on the marketplace, patients are not being treated and they're not at goal, and therefore, you see 18 million deaths worldwide because of ASCVD.

所以你是絕對正確的。這就是意圖。這就是我們看待它的方式。在本地，它看起來會非常不同，一個國家一個國家，一個系統一個系統，但這就是目標。最終，我們將改變 ASCVD 的格局，因為今天，即使市場上有藥物，患者也沒有得到治療，也沒有達到目標，因此，全世界有 1800 萬人死於 ASCVD。

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

您的下一個問題來自花旗銀行的 Andrew Baum。

Could you just outline for us the differences between this 15,000 VICTORION-2P and the ORION-4 trial for Leqvio? I'm assuming this is just a sort of marketing base Phase III to expand clinician experience, but maybe I've missed something different about the patient populations apart from the subtleties.

您能否為我們概述一下這個 15,000 VICTORION-2P 和用於 Leqvio 的 ORION-4 試驗之間的區別？我假設這只是一種擴大臨床醫生經驗的第三階段營銷基礎，但除了細微之處之外，我可能錯過了關於患者群體的一些不同之處。

And maybe if you have a second, perhaps you could comment on the ligelizumab surprise, given how robust the pretty large Phase IIb data was. Is this that the Xolair arm did better than expected? If you have any insights, it'd be great to hear.

也許如果你有第二個，也許你可以評論一下 ligelizumab 的驚喜，考慮到相當大的 IIb 期數據是多麼強大。這是 Xolair 手臂做得比預期好嗎？如果您有任何見解，很高興聽到。

Yes. Thanks, Andrew. John?

是的。謝謝，安德魯。約翰？

Yes, sure. Thanks for the question, Andrew. Specifically on Leqvio, as you know, the study ORION-4, which is being conducted in the U.K., is more of a population-based approach to looking at secondary prevention. And that is mostly in the U.K., with some patients in the U.S.

是的，當然。謝謝你的問題，安德魯。如您所知，特別是在 Leqvio 上，正在英國進行的 ORION-4 研究更多地是一種基於人群的二級預防方法。這主要發生在英國，也有一些患者在美國。

The V-2P is a broader patient population where we're going globally, not only in the U.S., but across major geographies throughout the world. So -- and we know that there are differences in practice patterns throughout the world. So what we intend to do is ensure we follow these patients and make sure that we have a clear understanding of the treatment for secondary prevention for Leqvio. So those are the approaches that we're taking difference, of ORION-4 versus -- Leqvio.

V-2P 是一個更廣泛的患者群體，我們正在走向全球，不僅在美國，而且在世界各地的主要地區。所以——我們知道世界各地的實踐模式存在差異。所以我們打算做的是確保我們跟踪這些患者，並確保我們對 Leqvio 的二級預防治療有一個清晰的了解。所以這些是我們正在採取不同的方法，ORION-4 與 - Leqvio。

And back on your question for ligelizumab and what we've seen. We started the Phase III study, PEARL 1 and PEARL 2, which were designed against the active comparator, which was omalizumab. These studies were based on primary endpoints that we saw through our Phase IIb study. And those -- that Phase IIb study had 380 patients and 80 patients per arm. And as we've actually demonstrated or showed during the fourth quarter, as we shared at the R&D Day, we did achieve the primary endpoint of superiority versus placebo, but we did not demonstrate superiority versus omalizumab.

回到你對 ligelizumab 的問題和我們所看到的。我們開始了 III 期研究 PEARL 1 和 PEARL 2，它們是針對活性比較藥物奧馬珠單抗設計的。這些研究基於我們通過 IIb 期研究看到的主要終點。而那些——IIb 期研究每組有 380 名患者和 80 名患者。正如我們在第四季度實際展示或展示的那樣，正如我們在研發日分享的那樣，我們確實實現了優於安慰劑的主要終點，但我們沒有展示出與奧馬珠單抗相比的優勢。

We're currently reviewing that data and we're evaluating the best potential for moving that forward. And as Vas stated earlier, we're advancing the studies in CIndU and food allergy, and they're continuing as planned.

我們目前正在審查這些數據，我們正在評估推動這一發展的最佳潛力。正如 Vas 之前所說，我們正在推進 CIndU 和食物過敏的研究，並且它們正在按計劃繼續進行。

And maybe, Andrew, just one additional point to John's comments. To your specific point, we did see omalizumab perform better in the Phase III study versus the Phase II study. So that is a leading hypothesis we have. But I think still more work to do to fully ascertain why we saw the difference between the Phase IIb in the New England Journal and the result that we saw in Phase III. So as soon as we have a better understanding, we'll of course share it. In the meantime, ligelizumab, we continue to develop it in food allergy and CIndU, given the lack of an IgE drug for those indications.

也許，安德魯，約翰的評論只是多一點。就您而言，我們確實看到奧馬珠單抗在 III 期研究中的表現優於 II 期研究。所以這是我們的主要假設。但我認為還需要做更多的工作來完全確定為什麼我們看到了新英格蘭期刊的 IIb 期和我們在 III 期看到的結果之間的差異。所以一旦我們有了更好的理解，我們當然會分享它。與此同時，由於缺乏針對這些適應症的 IgE 藥物，我們繼續在食物過敏和 CIndU 中開發它。

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

您的下一個問題來自 Redburn 的 Simon Baker。

It's a question on the impact of COVID, specifically to -- in 3 areas for you. Firstly, could you give us an update on the dynamic MS market as this affects Kesimpta? And also recruitment into the Phase III remibrutinib study that started in fourth quarter.

這是一個關於 COVID 影響的問題，特別是對您的 3 個方面的影響。首先，您能否向我們介紹一下動態 MS 市場的最新情況，因為這會影響 Kesimpta？並且還招募了從第四季度開始的 III 期 remibrutinib 研究。

And also, for Leqvio in the U.K., Marie-France, you mentioned the NHS non-COVID block is about to be released. But I just wondered how the significant backlogs within the U.K. health care system could potentially impact the rate at which you will accrue the target number of patients over the next few years.

此外，對於英國的 Leqvio，Marie-France，您提到 NHS 的非 COVID 區塊即將發布。但我只是想知道英國醫療保健系統內的大量積壓可能會如何影響未來幾年累積目標患者人數的速度。

Thank you, Simon. So first, Marie-France, on the MS market and Leqvio, NHS.

謝謝你，西蒙。首先是 MS 市場的 Marie-France 和 NHS 的 Leqvio。

Yes. So maybe I'll just start off by saying that we're all getting used to COVID. And I think not only the industry, but also health care systems in general, we're sort of learning to become more and more agile. But it is true that there are areas that are disproportionately impacted. And clearly, the dynamic multiple sclerosis market, if you look at it, it is still below pre-COVID levels. And we are also seeing, as you said, a delay in our Leqvio launch in the U.K. given this moratorium on anything that's not COVID related.

是的。所以也許我會先說我們都習慣了 COVID。而且我認為不僅行業，而且整個醫療保健系統，我們都在學習變得越來越敏捷。但確實有些領域受到了不成比例的影響。很明顯，動態多發性硬化症市場，如果你看一下，它仍然低於 COVID 之前的水平。正如你所說，我們還看到我們在英國推出 Leqvio 的時間有所延遲，因為暫停了與 COVID 無關的任何事情。

So ultimately, yes, it's true. I don't think for Kesimpta, it slowed us down. I can already say, for example, that in the beginning of the year, we already have all of our patients reverified. We've tried as much as possible be out there with physicians. Our share of voice is high. We have absolutely doubled down on patient services to make sure that patients are not left out in the cold in this whole sort of pandemic era. So I do think it's almost allowed us to basically rethink some of the way that we approach the market and do better. However, it's a clear reality on certain areas, and not only those.

所以最終，是的，這是真的。我不認為 Kesimpta，它讓我們慢了下來。例如，我已經可以說，在今年年初，我們已經對所有患者進行了重新驗證。我們已經盡可能多地與醫生在一起。我們的發言權很高。我們絕對加倍提供患者服務，以確保患者在整個大流行時代不會被冷落。因此，我確實認為這幾乎可以讓我們從根本上重新思考我們接近市場並做得更好的一些方式。然而，在某些領域，這是一個明確的現實，而不僅僅是那些領域。

For the U.K., as I said this morning, it hasn't really slowed us down on the implementation. I mean, we've been working really diligently in the background on things that we would have had to do anyway, right? So NHS guidelines, making sure that the communication is ready to go out. Looking at, for example, the patient digital identification. The NHS guidelines have already been written.

對於英國，正如我今天早上所說，它並沒有真正減慢我們的實施速度。我的意思是，我們一直在後台非常努力地處理我們無論如何都必須做的事情，對吧？所以 NHS 指導方針，確保通信準備好出去。例如，查看患者數字標識。 NHS 指南已經編寫完畢。

So I think when this moratorium is lifted -- and of course, yes, remember that this is all in the primary care sector. So our entire plan for the NHS is centered around the primary care physician, and that's where the moratorium is. So we're waiting for that to be lifted. But I do want to reassure the audience that we're not at a standstill. We're doing the things that we would have to do anyway and laying the groundwork for the future.

所以我認為，當這種暫停解除時——當然，是的，請記住，這一切都在初級保健部門。因此，我們對 NHS 的整個計劃都以初級保健醫生為中心，這就是暫停的地方。所以我們正在等待它被解除。但我確實想向觀眾保證，我們並沒有停滯不前。我們正在做我們無論如何都必須做的事情，並為未來奠定基礎。

And with -- maybe a last word on Kesimpta. We're bullish on our ability to double sales in the U.S. We've got approval in 63 countries around the world. We're working through reimbursement. And so we believe it's going to be a good year for Kesimpta despite the local, let's say, lockdowns or pandemic influence that we see across the globe.

還有——也許是關於 Kesimpta 的最後一句話。我們看好我們在美國的銷售額翻番的能力。我們已在全球 63 個國家/地區獲得批准。我們正在通過報銷工作。因此，我們相信這對 Kesimpta 來說將是豐收的一年，儘管我們在全球範圍內看到了當地的，比如說，封鎖或大流行的影響。

And then, John, on remibrutinib recruitment, any insights yet?

然後，約翰，關於瑞布替尼的招募，有什麼見解嗎？

Absolutely. Thanks for the question, Simon. The MS space is one that we know very well from our experience in the studies that we conducted across Gilenya, Mayzent as well as Kesimpta. We announced earlier in the year in 2021 that we were advancing with remibrutinib, which is our selective molecule BTK inhibitor, in the space. We had discussions in the middle of the year to late in the year with regulatory authorities. And we've already started recruiting at the end of the year.

絕對地。謝謝你的問題，西蒙。從我們在 Gilenya、Mayzent 和 Kesimpta 進行的研究中，我們非常了解 MS 空間。我們在 2021 年早些時候宣布，我們正在推進我們在該領域的選擇性分子 BTK 抑製劑瑞布替尼。我們在年中到年末與監管機構進行了討論。我們已經在年底開始招聘。

And we know the space well. We're confident that we can recruit in the MS space. And that we're excited to continue to fulfill the criteria in terms of advancing the recruitment for the MS patients for remibrutinib.

我們非常了解這個空間。我們有信心可以在 MS 領域進行招聘。而且我們很高興能夠繼續滿足標準，以促進招募多發性硬化症患者使用瑞布替尼。

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。

Yes. It's [Richard Wagner], Wolfe Research, for Tim Anderson. My question on M&A, whether you can say definitively that you won't do larger M&A, meaning something that would be, say, $30 billion or larger.

是的。我是 [Richard Wagner]，Wolfe Research，Tim Anderson。我關於併購的問題是，你是否可以明確地說你不會進行更大規模的併購，也就是說，比如 300 億美元或更大的併購。

Yes. Thanks for the question, Richard. We don't have plans to do "larger M&A." Hard to sign up for specific threshold given the dynamics in the market. But our focus is not larger M&A. Our focus is bolt-on. Bolt-on deals, most of the deals we've done, as I mentioned earlier, have been sub-$1 billion upfront with payouts for the total deal value of less than $2 billion, as in recent times, including the 4 deals that we recently signed. And we continue to focus our energies there.

是的。謝謝你的問題，理查德。我們沒有計劃進行“更大的併購”。鑑於市場動態，很難註冊特定的門檻。但我們的重點不是更大的併購。我們的重點是螺栓固定。正如我之前提到的，我們已經完成的大多數交易都是附加交易，預付款低於 10 億美元，而最近支付的總交易價值不到 20 億美元，包括我們最近完成的 4 筆交易最近簽了。我們繼續將精力集中在那裡。

We look at larger assets. Valuations are stretched, expectations remain high. Harder to make the numbers work to create value for shareholders and an attractive profile for Novartis. But we continue to assess those, let's call, the larger bolt-on deals. And then beyond that, we are not looking at large M&A, no, at this time.

我們著眼於更大的資產。估值偏高，預期仍然很高。更難讓這些數字為股東創造價值並為諾華公司創造有吸引力的形象。但我們繼續評估那些，讓我們稱之為更大的附加交易。除此之外，我們目前不考慮大型併購。

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

您的下一個問題來自 Berenberg 的 Kerry Holford。

Question please on Sandoz. In your presentation, Harry, you're speaking of stabilization in Q4. But the 2022 guidance in this division is somewhat disappointing. I wonder if you can walk us through the drivers on your guidance for operating profit decline this year. Is that predominantly price pressure? More of the same? Could be disruption? Or is there some element of more investment required to see the top line of this division return to growth? I guess, specifically, I'm looking what you expect to get more difficult for Sandoz this year since last, given this time stabilization sign you mentioned in Q4.

請向 Sandoz 提問。在你的演講中，Harry，你說的是第四季度的穩定。但該部門的 2022 年指導有些令人失望。我想知道您是否可以向我們介紹您對今年營業利潤下降的指導的驅動因素。主要是價格壓力嗎？更多相同？可能是中斷嗎？或者是否需要更多投資才能看到該部門的收入恢復增長？我想，具體來說，鑑於您在第四季度提到的這個時間穩定跡象，我正在尋找自去年以來山德士今年會變得更加困難的情況。

And then just a very quick follow-up. Can we assume the contract manufacturing revenue reclassification you mentioned in the quarter is a one-off event?

然後只是一個非常快速的跟進。我們可以假設您在本季度提到的合同製造收入重新分類是一次性事件嗎？

Thanks, Kerry. So maybe first on Sandoz. Richard, do you want to start? And then maybe Harry can chime in if anything...

謝謝，克里。所以也許首先在 Sandoz 上。理查德，你想開始嗎？然後也許哈利可以插話……

Yes. Sure. Thank you, Vas. And thank you for the question, Kerry. Yes, as I said, look, Q4, we saw things returning back to a more normal state of affairs and a nice, I guess, solid performance in quarter 4.

是的。當然。謝謝你，瓦斯。謝謝你的問題，克里。是的，正如我所說，看，第四季度，我們看到事情恢復到更正常的狀態，我猜第四季度的表現不錯。

As we go into 2022, I mean, we're seeing good growth from the rest of the world. And really, the challenge continues to be the U.S. And that's slowly -- the impact of price clearly drives the issues in the U.S., but we're slowly stabilizing. And so really I see 2022 is a year where the rate of decline in the U.S. does stay low, but it does drag down the overall business. Price still is a significant impact.

我的意思是，隨著我們進入 2022 年，我們看到來自世界其他地區的良好增長。事實上，挑戰仍然是美國。而且這很緩慢——價格的影響顯然推動了美國的問題，但我們正在慢慢穩定下來。所以我真的認為 2022 年是美國的下降率確實保持在低水平的一年，但它確實拖累了整體業務。價格仍然是一個重大影響。

And also bear in mind, 2022, we don't see many significant launches. It's still a fairly quiet year in terms of LOE launches. So really, the impact on bottom line is really a mixture of price and mix. And we expect that then to slowly start changing as we come out of '23 into '24 as the biologics pipeline starts to kick in again and the U.S. continue at its stabilize journey. And we see accelerated growth then in Europe and the rest of the world.

還要記住，2022 年，我們看不到很多重大的發布。就 LOE 發布而言，這仍然是相當平靜的一年。所以說真的，對底線的影響實際上是價格和組合的混合。我們預計，隨著生物製劑管道再次開始啟動和美國繼續其穩定之旅，隨著我們從 23 年進入 24 年，這種情況會慢慢開始改變。我們看到歐洲和世界其他地區的增長加速。

Thanks, Richard. And then Harry, on contract manufacturing? And I don't know if you have any other comments on Sandoz.

謝謝，理查德。然後哈利，合同製造？我不知道您是否對 Sandoz 有任何其他意見。

No. I think Richard said it all on Sandoz.

不，我認為理查德在 Sandoz 上說了這一切。

In terms, Kerry, of contract manufacturing, we have reported relatively small contract manufacturing business within other revenues. And now that we may increase over the next years a little bit that business, we basically chose to change representation, split up the sales and COGS.

就合同製造而言，我們在其他收入中報告了相對較小的合同製造業務。現在我們可能會在未來幾年增加一點業務，我們基本上選擇改變代表，拆分銷售和 COGS。

And we also transparently show that, actually, on Page 13 of the condensed financial report, in established medicines, you see under the contract manufacturing line, $108 million in quarter 4, which is kind of the full year '21 as we decided in the year that maybe over the next few years, this may increase. So that's why we changed that.

而且我們還透明地表明，實際上，在簡明財務報告的第 13 頁上，在已建立的藥品中，您可以在合同生產線下看到，第 4 季度為 1.08 億美元，這是我們在 21 年全年決定的可能在接下來的幾年中，這可能會增加。所以這就是我們改變它的原因。

It doesn't change the full year number for the company. It changes in the quarter basically by one point on the company and the 2 divisions. And so we will -- you will see that as we go forward, how this is developing. And from that standpoint, we thought it's a better representation as we go forward.

它不會改變公司的全年數字。公司和 2 個部門在本季度基本上變化了 1 個百分點。因此，我們將——你會看到隨著我們前進，這是如何發展的。從這個角度來看，我們認為這是我們前進的更好的代表。

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

您的下一個問題來自高盛的 Keyur Parekh。

Two if I may. First, kind of, Vas, in your introductory comments, you spoke about your aspiration to be a top 3 innovator. I was wondering if you might be able to give us some more details around kind of how do you define a top 3 innovator. Is that in terms of number of new drugs approved? Is that commercial value of the pipeline? Just any -- just your thoughts around kind of how do you define that.

如果可以的話，兩個。首先，Vas，在您的介紹性評論中，您談到了成為前三名創新者的願望。我想知道您是否可以向我們提供更多關於您如何定義前 3 名創新者的詳細信息。是根據批准的新藥數量嗎？這是管道的商業價值嗎？隨便——只是你對如何定義它的想法。

And then secondly, as we look forward to the Phase III study readout for iptacopan, what should be our kind of expectations around the profile for that? Should we be looking at superiority? Should we be looking at something else? Just kind of your confidence around that and where should our expectations be for that molecule.

其次，當我們期待 iptacopan 的 III 期研究結果時，我們應該對此有什麼樣的期望？我們應該看優越感嗎？我們應該看別的東西嗎？只是您對此的信心以及我們對該分子的期望應該在哪裡。

Yes. Thanks, Keyur. On the first one, a few measures on our minds. One is the replacement power and can we be a leader in consistent replacement power of our sales? I think replacement power and/or freshness index are valuable measures of the power of an innovation engine to replace sales within our sector and then ultimately to grow the sales of the company.

是的。謝謝，凱爾。在第一個方面，我們考慮了一些措施。一是替代能力，我們能否成為銷售持續替代能力的領導者？我認為替代能力和/或新鮮度指數是衡量創新引擎在我們行業內替代銷售並最終增加公司銷售額的重要指標。

Second, we're very focused on the value per NME that we are able to deliver. We over the last 5 years, have been the leading company in the sector in the number of NMEs approved, but we'd like to be the leader in the value per NME or peak sales per NME, put in another way, that we're delivering to the market.

其次，我們非常關注我們能夠提供的每個 NME 的價值。在過去的 5 年中，我們在獲批 NME 數量方面一直是該行業的領先公司，但我們希望成為每個 NME 的價值或每個 NME 的峰值銷售額的領導者，換句話說，我們重新投放市場。

And of course, ultimately, this all leads to long-term sales growth and our ability to have an innovation engine that can drive that sales growth where we want to consistently be. But I would say replacement power and value per NME are high measures on our mind.

當然，最終，這一切都會帶來長期的銷售增長，以及我們擁有能夠推動銷售增長的創新引擎的能力。但我想說的是，每個 NME 的替代能力和價值是我們心中的重要衡量標準。

In terms of the Phase III profile of iptacopan, John?

就 iptacopan 的 III 期概況而言，John?

Yes. Thanks, Keyur. As we look at the iptacopan and the way that we're looking at the overall profile, obviously, we're looking at the overall unmet needs of the patient. As you know, this is a factor B that is actually targeting the alternative complement pathway. We're looking at both extravascular and intravascular hemolysis for PNH in this specific indication.

是的。謝謝，凱爾。當我們查看 iptacopan 以及我們查看整體概況的方式時，顯然，我們正在查看患者的整體未滿足需求。如您所知，這是一個實際上針對替代補體途徑的因子 B。在這個特定的適應症中，我們正在研究 PNH 的血管外和血管內溶血。

Also, as we think about the renal indications, we're looking at it from the standpoint of reduction in terms of proteinuria. And it could be in a couple of different ways as we know that these patients have a significant unmet need as, one, that they actually may need something more than what's the current standard of care, which is through ACE inhibitors and ARBs. So this could be a combination approach moving forward.

此外，當我們考慮腎臟適應症時，我們從減少蛋白尿的角度來看待它。可能有幾種不同的方式，因為我們知道這些患者有明顯的未滿足需求，其中一種是，他們實際上可能需要的東西比目前的護理標準更多，即通過 ACE 抑製劑和 ARB。因此，這可能是一種向前發展的組合方法。

The second way of looking at this, not only in terms of unmet medical need, is also the route of administration or in terms of the convenience for the patients. As we think about the approach, many patients actually are requiring the subcu administration, which could take up to 60 minutes. And having an oral administration twice a day would be much easier in terms of the approach.

第二種看待這一點的方式，不僅是在未滿足的醫療需求方面，也是給藥途徑或患者的便利性方面。當我們考慮這種方法時，許多患者實際上需要 subcu 給藥，這可能需要長達 60 分鐘。就方法而言，每天兩次口服給藥會容易得多。

And thirdly is evaluating the safety profile as we look moving forward. And we'll find out more about the safety profile as we read out in our study. So that's the way that we're looking at iptacopan overall across the indications for PNH as well as C3G, IgA and other renal indications.

第三是在我們展望未來時評估安全狀況。正如我們在研究中所宣讀的那樣，我們將了解更多關於安全概況的信息。這就是我們在 PNH 以及 C3G、IgA 和其他腎臟適應症的適應症中整體看待 iptacopan 的方式。

Your next question comes from Wimal Kapadia from Bernstein.

您的下一個問題來自 Bernstein 的 Wimal Kapadia。

So I just want to touch on PSMA. So you have an interesting readout, PSMAfore, potentially late 2022. I mean, how should we be thinking about the incremental efficacy with these current benchmarks? And then, in particular, how should we be thinking about the pre-taxane setting from a potential perspective versus the post-taxane setting?

所以我只想談談 PSMA。所以你有一個有趣的讀數，PSMAfore，可能在 2022 年末。我的意思是，我們應該如何考慮這些當前基準的增量功效？然後，特別是，我們應該如何從潛在的角度考慮紫杉烷前環境與紫杉烷後環境？

And then just tied to that, the launch of -- from the VISION study. Is it fair to assume Lutathera trajectory is a fair benchmark? Or just given prostate is a larger indication, the trajectory should look a little bit different, with more sustained growth beyond the initial ramp from saturation of clinics with capability?

然後就與此相關，推出了——來自 VISION 研究。假設 Lutathera 軌跡是一個公平的基準是否公平？或者只是考慮到前列腺是一個更大的適應症，軌跡應該看起來有點不同，從有能力的診所飽和的最初斜坡開始，會有更持續的增長？

Yes. Thanks, Wimal. So maybe, Susanne, first on the overall story with Lu-PSMA and the launch of the VISION study. And then I'll hand it to John on the specific questions on pre- and post-taxane. Susanne?

是的。謝謝，維馬爾。所以，Susanne，也許首先是關於 Lu-PSMA 的整體故事和 VISION 研究的啟動。然後我將把關於紫杉烷前後的具體問題交給約翰。蘇珊？

Susanne, are you there?

蘇珊，你在嗎？

Sorry, I was on mute. So lutetium-PSMA has demonstrated very strong data in the metastatic castrated-resistant prostate cancer population, as you know, with significant radiographic PFS and OS. So we know in this population, there's basically no alternative and lutetium-PSMA has demonstrated superiority versus the standard of care. So we expect there, quite big interest. And we have started managed access programs where we already see quite high demand.

對不起，我靜音了。因此，如您所知，镥-PSMA 已在轉移性去勢抵抗性前列腺癌人群中證明了非常強大的數據，具有顯著的放射學 PFS 和 OS。所以我們知道，在這個人群中，基本上沒有其他選擇，镥-PSMA 已證明優於護理標準。所以我們期望在那裡，相當大的興趣。我們已經開始了託管訪問計劃，我們已經看到了相當高的需求。

So therefore, when you ask me about the uptake, it will be probably steadily going up. We don't expect a big bolus. This is fourth line prostate cancer patients. But of course, incidence of prostate cancer is much higher than, for example, neuroendocrine tumors. And therefore, I think we see different dynamics in the uptake. Of course, it's a smaller part, it's the last line of prostate cancer. But we expect continued growth, and not like a bolus and then stability. It's a very different population than GEP-NET.

因此，當你問我關於吸收的問題時，它可能會穩步上升。我們預計不會有大的推注。這是四線前列腺癌患者。但當然，前列腺癌的發病率遠高於神經內分泌腫瘤等。因此，我認為我們看到了不同的吸收動態。當然，它是一個較小的部分，它是前列腺癌的最後一道防線。但我們預計會繼續增長，而不是像推注然後穩定。這是一個與 GEP-NET 非常不同的人群。

And maybe just a comment before I hand over to John on the setting. I mean, the current indication that we have filed for would really in last line after androgen therapy and taxane chemotherapy. And therefore, of course, with the profile that we see on lutetium-PSMA, we would aim to go earlier. And certainly, the pre-taxane setting is one of the settings that is significantly bigger than what we have filed for in the current indication.

也許只是在我將設置交給約翰之前的評論。我的意思是，我們目前申請的適應症在雄激素治療和紫杉烷化療之後真的會排在最後一行。因此，當然，根據我們在 lutetium-PSMA 上看到的配置文件，我們的目標是更早進行。當然，紫杉烷前設置是比我們在當前指示中申請的設置要大得多的設置之一。

So with that, John, maybe over to you. Maybe a few words on PSMAfore.

所以，約翰，也許交給你了。也許在 PSMAfore 上說幾句。

Sure. Happy to talk about PSMAfore. Maybe to start off, just to think about prostate cancer. As we know, 80% of prostate cancer is actually express PSMA. So that's a starting point in the pathophysiology. What we saw in the third line, as Susanne expressed, is we saw that they had 38% improvement in overall survival and 60% in terms of radiographic progression-free survival as well as combination of OS. That is the starting point.

當然。很高興談論 PSMAfore。也許開始，只是想想前列腺癌。眾所周知，80% 的前列腺癌實際上是表達 PSMA。所以這是病理生理學的起點。正如 Susanne 所說，我們在第三行中看到的是，我們看到他們的總生存期提高了 38%，在放射學無進展生存期以及 OS 組合方面提高了 60%。那是起點。

We know that there are a number of patients that are in need of additional treatments, whether that's in the pre-taxane setting or in the first-line setting, especially given the toxicity of the taxanes and chemotherapy. And what we know is radioligand therapy has less adverse events than compared to chemotherapy.

我們知道有許多患者需要額外的治療，無論是在紫杉烷治療前還是一線治療，尤其是考慮到紫杉烷和化療的毒性。我們所知道的是，與化療相比，放射性配體治療的不良事件更少。

So we've already started recruitment in the pre-taxane study, and we're hoping to read out before the end of the year for the second line treatment. And then we're also looking at first-line treatment in terms of hormone-sensitive population. And that study is also advancing. And we're -- in addition to those studies, we're also looking at studies in terms of patients who have not had metastases in terms of prostate cancer. So I think this is going to be a very broad program as we move forward for the lutetium-PSMA.

所以我們已經開始在紫杉烷前研究中進行招募，我們希望在年底前宣讀二線治療。然後我們也在關注激素敏感人群的一線治療。這項研究也在推進。而且我們 - 除了這些研究之外，我們還在研究針對沒有前列腺癌轉移的患者的研究。所以我認為隨著我們推進镥-PSMA，這將是一個非常廣泛的計劃。

Thank you, John. Thank you, Wimal.

謝謝你，約翰。謝謝你，維馬爾。

So we have still quite a few people in the queue. (Operator Instructions) Next question, operator?

所以我們還有不少人在排隊。 （操作員說明）下一個問題，操作員？

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

您的下一個問題來自瑞士信貸的 Matt Weston。

My question is on ensovibep. And Harry or vas, I'd be very interested to understand how you've integrated it into guidance. I can see from your slides that you've given it a $1 billion on probability of just peak sales potential. And obviously, if you're able to achieve regulatory emergency use authorization, we could see significant bolus orders. And so I'd love to know what you've taken into account when you set guidance for 2022, too.

我的問題是關於ensovibep。還有 Harry 或 vas，我很想了解您如何將其整合到指導中。我可以從你的幻燈片中看到，你已經為它提供了 10 億美元的銷售潛力。顯然，如果您能夠獲得監管緊急使用授權，我們可以看到大量的推注訂單。因此，我也很想知道您在製定 2022 年指導方針時也考慮了哪些因素。

Yes. Thank you, Matthew, and I can take that. So we've not included ensovibep in our guidance -- any of the guidance that we've provided today. I think as we understand better, as we move through the emergency use authorization application and review process, ultimately, understand the FDA's decision and then the potential contracting we would have with the U.S. as well as other interested parties around the world.

是的。謝謝你，馬修，我可以接受。所以我們沒有在我們的指導中包括 ensovibep——我們今天提供的任何指導。我認為隨著我們更好地理解，隨著我們通過緊急使用授權申請和審查過程，最終了解 FDA 的決定，然後了解我們與美國以及世界各地其他相關方的潛在合同。

We've had discussions with a number of other governments around the world around the medicine. But I would say most of those governments have centered their view on how the FDA ultimately views the EUA application, if they were going to make emergency orders. So we think it's prudent right now not to include it. And then once we understand the dynamics better over the course of Q1, we hope, or into Q2, we would then update accordingly.

我們已經與世界各地的許多其他政府就該藥物進行了討論。但我想說，如果他們要發布緊急命令，大多數政府都將他們的觀點集中在 FDA 最終如何看待 EUA 申請上。所以我們認為現在不包括它是謹慎的。然後，一旦我們更好地了解了第一季度的動態，我們希望，或者進入第二季度，我們會相應地進行更新。

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

您的下一個問題來自摩根大通的 Richard Vosser。

So just a question on price pressure from ex U.S. governments, et cetera. I mean, they've been pretty hit by COVID and COVID expenses. After the great financial crisis, we saw some increased pressure on drug prices. Are we going to see something like that? Are there any murmurings from governments on pricing pressure generally?

所以只是一個關於前美國政府等價格壓力的問題。我的意思是，他們受到 COVID 和 COVID 費用的嚴重打擊。在大金融危機之後，我們看到藥品價格的壓力有所增加。我們會看到類似的東西嗎？政府是否普遍對價格壓力表示不滿？

Well, I can start and say as far as my discussions have gone on with various health officials in Europe, not heard an increased focus or a shift in terms of the support for innovative medicines and enabling medicines that have broad access or improved access. Certainly, that's a priority for President Macron and his European Commission President.

好吧，我可以開始說，就我與歐洲多位衛生官員的討論而言，沒有聽到對創新藥物的支持增加或轉移，以及廣泛使用或改善可及性的使能藥物。當然，這是馬克龍總統和他的歐盟委員會主席的優先事項。

But maybe Marie-France, do you have any thoughts or insights on this?

但也許 Marie-France，你對此有什麼想法或見解嗎？

Yes. I mean, I just think in general, we always have to be prepared. I mean, we do more and more have to make the case, or we see limitations on reimbursement in terms of line of therapy, et cetera, et cetera. Obviously, we have a lot of experience, and we're very used to that in the European landscape. You see a lot of tough negotiations happening in China.

是的。我的意思是，我只是認為總的來說，我們總是必須做好準備。我的意思是，我們要做的事情越來越多，否則我們會看到治療線等方面的報銷限制，等等。顯然，我們有很多經驗，而且我們在歐洲的環境中已經很習慣了。你看到在中國發生了很多艱難的談判。

So I would say it's a little bit almost like the ticket to entry is making sure that the value of our products is recognized, that we're focused on value-based pricing, which I think is something that Novartis has been very diligent about, and making sure that access is really top of mind on any strategy when it comes to product launch or making sure that more patients can reach products faster.

所以我想說這有點像進入的門票是確保我們產品的價值得到認可，我們專注於基於價值的定價，我認為這是諾華一直非常努力的事情，並確保在產品發布或確保更多患者能夠更快地獲得產品時，訪問確實是任何策略的首要考慮因素。

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

您的下一個問題來自德意志銀行的 Emmanuel Papadakis。

Maybe I'll take one on ianalumab and the decision to progress into Phase III. I guess, question around design and timing. You've published data that look, I would say, better in patients with less advanced disease. So have you reached a decision yet about the Phase III design? At what breadth of enrollment is that likely to include in terms of the patient population? And therefore, what proportion of the Sjögren’s population, which is pretty large, that might -- that Phase III trial might apply to?

也許我會接受 ianalumab 和進入 III 期的決定。我想，關於設計和時間的問題。你發表的數據看起來，我想說，在疾病較輕的患者身上效果更好。那麼，您對第三階段的設計做出決定了嗎？就患者群體而言，這可能包括多大範圍的登記？因此，Sjögren 的人口比例相當大，這可能適用於 III 期試驗？

And then just in terms of timing, you, I think, told us at the R&D Day, 2026 was the likely timing for a potential Phase III readout. Is there any way that could be accelerated, for example, an interim surrogate or biomarker data? Since that would imply a pretty long Phase III time line.

然後就時間而言，我認為你在研發日告訴我們，2026 年可能是第三階段讀數的可能時間。有什麼方法可以加速，例如臨時替代或生物標誌物數據？因為這意味著第三階段的時間線相當長。

Thank you, Emmanuel. Very good questions. John, on ianalumab Phase III design for Sjögren’s?

謝謝你，伊曼紐爾。非常好的問題。約翰，關於 Sjögren 的 ianalumab III 期設計？

Yes. As we think about ianalumab, and as Vas said earlier, we're excited about a number of indications in Sjögren’s syndrome, lupus nephritis and SLE. Specifically, as you asked about Sjögren’s syndrome, as you know, we've advanced based on results that we've seen from our Phase II study. These are patients who actually have had high STI scores. And that's the specific population that we're targeting, moving forward in this population. We are going to start recruiting patients in the second half of this year.

是的。當我們想到 ianalumab 時，正如 Vas 之前所說，我們對乾燥綜合徵、狼瘡腎炎和 SLE 的許多適應症感到興奮。具體來說，正如你所問的關於乾燥綜合徵的問題，如你所知，我們已經根據我們從 II 期研究中看到的結果取得了進展。這些患者實際上具有高 STI 評分。這就是我們針對的特定人群，在這個人群中向前發展。我們將在今年下半年開始招募患者。

In terms of advancing, I think the balance here is the largest Sjögren’s syndrome Phase III study that's been conducted -- actually, I should say, the largest study, not Phase III, but the largest study that's been conducted has been conducted by us. And we want to ensure that there is consistency in terms of these patients that we're recruiting because Sjögren’s is a very diverse population of patients.

在推進方面，我認為這裡的平衡是已經進行的最大的干燥綜合徵 III 期研究——實際上，我應該說，最大的研究，不是 III 期，但我們已經進行了最大的研究。我們希望確保我們正在招募的這些患者的一致性，因為 Sjögren 是一個非常多樣化的患者群體。

We've guided the results in 2026, and we will update as we find the patients and how recruitment goes. But we are using strict criteria for inclusion to ensure that we get the best results moving forward. Currently, we are expecting results in '26.

我們已經指導了 2026 年的結果，我們將在找到患者以及招募情況時進行更新。但我們正在使用嚴格的納入標準，以確保我們在前進中獲得最佳結果。目前，我們期待 26 年的結果。

I mean, I think one of the dynamics I've learned is how important it is to have well-trained centers here that really ensure that they apply the STI and some of the other measures in a consistent way. So I think we want to be appropriately cautious on our time line. And then, of course, as we learn more, as John said, we'll provide updates on ianalumab across all of the indications that we take it forward in.

我的意思是，我認為我學到的動態之一是在這裡擁有訓練有素的中心非常重要，以真正確保他們以一致的方式應用 STI 和其他一些措施。所以我認為我們希望在時間線上保持適當的謹慎。然後，當然，隨著我們了解更多，正如約翰所說，我們將提供有關 ianalumab 的更新，涵蓋我們推進它的所有跡象。

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

您的下一個問題來自摩根士丹利的 Mark Purcell。

Entresto China, can you help us understand the size of the opportunity in hypertension? But when the LOE timing is going to kick in? And on the basis of that, the pivot opportunity within the retail pharmacy setting to maintain your momentum in China?

Entresto China，您能幫助我們了解高血壓的機會大小嗎？但是 LOE 時機何時開始？在此基礎上，零售藥店環境中保持您在中國發展勢頭的關鍵機會？

And then just quickly, Vas, in terms of clarification. In terms of the Sandoz considerations for counterparties, what should we expect next in terms of biosimilar data? And what are the key LOE launches coming up in '23 and beyond?

然後很快，Vas，在澄清方面。在山德士對交易對手的考慮方面，我們接下來在生物仿製藥數據方面應該期待什麼？ 23 年及以後推出的關鍵 LOE 是什麼？

Yes. Absolutely, Mark. So first, on the Entresto China, Marie-France?

是的。絕對的，馬克。那麼首先，關於 Entresto China，Marie-France？

Yes. So the opportunity, certainly from a volume perspective, is significant, right? So we're moving the population from 7 million to 8 million heart failure patients to about [240] hypertension patients. And as I said before in my comments, hypertensive patients in China are really not well controlled. So there is a big opportunity. Obviously, there was a significant price concession as we listed NRDL. But we do think that it is a worthwhile proposition just because there's an opportunity to just expand to such a broad, broad population of patients.

是的。所以從數量的角度來看，這個機會很重要，對吧？因此，我們正在將人口從 700 萬到 800 萬心力衰竭患者轉移到大約 [240] 名高血壓患者。而且正如我之前在評論中所說，中國的高血壓患者確實沒有得到很好的控制。所以有很大的機會。顯然，當我們列出國家醫保目錄時，價格有了很大的讓步。但我們確實認為這是一個值得的提議，因為有機會擴展到如此廣泛的患者群體。

So we are -- we have broadened our footprint as well. We're making the necessary investments. We also want to make sure that we have the right digital tools in place. As you know, we have a cooperation with Tencent where we're looking, of course, Entresto-independent, but looking at making sure that heart failure patients can be more in control of their own monitoring. So there are a lot of activities in this space. As you know, in China, CVD is a major -- cardiovascular disease is a major problem with massive costs.

所以我們 - 我們也擴大了我們的足跡。我們正在進行必要的投資。我們還想確保我們擁有正確的數字工具。如您所知，我們與騰訊有合作，當然，我們希望獨立於 Entresto，但希望確保心力衰竭患者能夠更好地控制自己的監測。所以這個空間有很多活動。如您所知，在中國，心血管疾病是一個大問題——心血管疾病是一個需要巨額費用的大問題。

And when it comes to the patent situation in China, China is hard to give a definitive answer. We are obviously working to secure RDP in China, and I think that's an industry-wide initiative. So there are some question marks around until when. And it certainly -- couldn't give you guidance on that here today.

而談到中國的專利情況，中國很難給出明確的答案。我們顯然正在努力在中國確保 RDP，我認為這是一項全行業的舉措。所以直到什麼時候都有一些問號。它當然-- 今天無法在此為您提供指導。

But the opportunity is significant. We're thrilled about it. This was, as we said, a potential upside for us, and could be up to about 1/3 of our, let's say, growth in Entresto for this year.

但機會是巨大的。我們對此感到非常興奮。正如我們所說，這對我們來說是一個潛在的上升空間，並且可能高達我們今年 Entresto 增長的 1/3 左右。

Thanks, Marie-France. And then on Sandoz biosimilars upcoming launches, Richard?

謝謝，瑪麗-法蘭西。然後關於即將推出的 Sandoz 生物仿製藥，Richard？

Thanks, Vas. Really, the next launches are really adalimumab and natalizumab coming in, I guess, late '23, into '24. So as I think I commented earlier, that, that's really the start of the next wave of biosimilars that should start accelerating both our top line and clearly the margin expansion for the business. And clearly, we'll update as we file and move those products forward.

謝謝，瓦斯。真的，下一次發布真的是阿達木單抗和那他珠單抗，我猜是 23 年末到 24 年。因此，正如我之前評論的那樣，這確實是下一波生物仿製藥的開始，應該開始加速我們的收入和業務的利潤率擴張。很明顯，我們將在提交文件並推進這些產品時進行更新。

Thanks, Mark. Thanks, Richard. Thank you, Mark.

謝謝，馬克。謝謝，理查德。謝謝你，馬克。

I think we have time for -- I don't know how many more we have in the queue. But operator, let's take the next question, and we'll keep going till the mid of the hour.

我想我們有時間——我不知道我們還有多少人在排隊。但是接線員，我們來回答下一個問題，我們會一直講到半點。

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

您的下一個問題來自法國興業銀行的 Florent Cespedes。

A quick follow-up on China, please. Could you please elaborate on, beyond Entresto, which are the growth drivers there and potential risk? And how you see the momentum in China?

請快速跟進中國。您能否詳細說明，除了 Entresto，還有哪些增長動力和潛在風險？您如何看待中國的發展勢頭？

Marie-France, do you want to take that on Pharma China?

Marie-France，你想對 Pharma China 採取這種態度嗎？

Yes. So we've got 3 main growth drivers for the Pharma business in China: Cosentyx, Entresto and Lucentis. And all 3 products are showing strong growth. I mean, as we mentioned before, they were all affected in Q4. But Q4 is also normally the lowest quarter in the year for us. So we talked about the budget constraints for Cosentyx. We've seen the rebound in Q1 for Entresto, the NRDL listing and the stock compensation. And Lucentis was due to COVID lockdowns.

是的。因此，我們有 3 個主要的中國醫藥業務增長動力：Cosentyx、Entresto 和 Lucentis。並且所有 3 種產品都呈現出強勁的增長勢頭。我的意思是，正如我們之前提到的，它們在第四季度都受到了影響。但對我們來說，第四季度通常也是一年中最低的季度。所以我們談到了 Cosentyx 的預算限制。我們已經看到 Entresto 在第一季度的反彈、國家醫保目錄的上市和股票補償。 Lucentis 是由於 COVID 封鎖造成的。

But the one thing I'll say about China is that, going forward and giving the fact that the country is now so open to innovation, we are now thinking about China as we think about any other country. So when we look forward at our portfolio, whether that's Leqvio, we just received the launch of -- or the approval for Kesimpta, we are thinking about our portfolio in China in the same way as we're thinking about our portfolio in the U.S. and Europe.

但關於中國，我要說的一件事是，展望未來，考慮到這個國家現在對創新如此開放的事實，我們現在正在考慮中國，就像我們考慮其他任何國家一樣。因此，當我們展望我們的投資組合時，無論是 Leqvio，我們剛剛收到了 - 或 Kesimpta 的批准，我們正在考慮我們在中國的投資組合，就像我們在考慮我們在美國的投資組合一樣和歐洲。

So going forward, that's what you can expect, the 3 growth drivers, maybe the big exception is Lucentis, which continues to be a strong growth driver for us in China. And that's where the focus is, that's where we're investing and that's where our footprint is working.

所以展望未來，這就是你可以期待的三大增長動力，也許最大的例外是 Lucentis，它仍然是我們在中國的強勁增長動力。這就是重點所在，這就是我們投資的地方，也是我們的足跡所在的地方。

Thanks, Marie-France.

謝謝，瑪麗-法蘭西。

So next, we'll go to -- I think we have 2 more first-time questions. Next question, operator?

所以接下來，我們會去——我想我們還有兩個第一次問的問題。下一個問題，接線員？

Your next question comes from Peter Welford from Jefferies.

您的下一個問題來自 Jefferies 的 Peter Welford。

One for Harry, really, the outlook for Innovative Medicines, the outlook for the core operating income, mid- to high single digits is sort of slightly above sales growth. Obviously, this year, you started similar, but you delivered close to 10%. Wondered if You could talk a little bit about what we should be thinking about the greater investments, I guess, you're making this year, which, if you like, constrained perhaps the margin expansion versus the benefit we saw in '21, the result in that mid- to high single-digit growth. Or is it just conservatism on your part?

哈利的一個，真的，創新藥物的前景，核心營業收入的前景，中高個位數略高於銷售增長。很明顯，今年，你們開始的時候也差不多，但交付率接近 10%。想知道你是否可以談談我們應該考慮的更多投資，我猜，你今年所做的，如果你願意，這可能限制了利潤率擴張與我們在 21 年看到的收益，導致中高個位數的增長。還是只是你的保守主義？

Thanks, Peter. Harry?

謝謝，彼得。哈利？

Yes. Thank you, Peter. So of course, always a fine balance, right? As we know, in pharma companies, one can get almost any kind of core margin one would like to have. But it's always this very delicate balance between investing and also driving, of course, productivity as we do.

是的。謝謝你，彼得。所以當然，總是一個很好的平衡，對吧？眾所周知，在製藥公司中，人們幾乎可以獲得任何想要的核心利潤。但是，在投資和推動生產力之間總是存在這種非常微妙的平衡，當然，就像我們所做的那樣。

And so overall, we have made significant strides on the core margin improvement. As Vas shared in one of his earlier charts, the 180 basis point in '19, 220 basis point in '20 and then 130 basis point last year. And a part of that was also some restricted investments, if you will, due to the pandemic situation.

因此，總體而言，我們在提高核心利潤率方面取得了重大進展。正如 Vas 在他早期的一張圖表中所分享的那樣，19 年為 180 個基點，20 年為 220 個基點，然後是去年的 130 個基點。如果你願意的話，由於大流行的情況，其中一部分也是一些受限的投資。

So we always ensure that we invest appropriately in the R&D line, certainly. And we have to ensure that the launches are getting very well supported. And we have fantastic launches that Marie-France, Susanne and her teams -- and their teams are driving. So I would expect each of the next years in Innovative Medicines, some good margin improvement, but of course, not to the level we have seen over the last 2, 3 years. So it's a balance and the investments are clearly in the pipeline and the launches. Thank you.

因此，我們始終確保我們對研發線進行適當投資，當然。我們必須確保發布得到很好的支持。我們有 Marie-France、Susanne 和她的團隊——以及他們的團隊正在推動的精彩發布。因此，我預計創新藥物接下來的每一年都會有一些不錯的利潤率提高，但當然，不會達到我們在過去 2 年、3 年看到的水平。所以這是一個平衡，投資顯然正在籌備和發布中。謝謝你。

Thanks, Harry. And then we have time -- thanks, Peter. Last question, operator?

謝謝，哈利。然後我們有時間-- 謝謝，彼得。最後一個問題，接線員？

Your last question today comes from the line of Seamus Fernandez from Guggenheim.

你今天的最後一個問題來自古根海姆的 Seamus Fernandez。

So just wanted a couple of pipeline questions very quickly. Just in terms of the differentiation, what makes ianalumab unique from other APO or BAFF compounds that have failed in similar type indications, particularly in lupus? I think we've seen a number of challenges there.

所以很快就想要幾個管道問題。就差異而言，是什麼讓ianalumab 與其他在類似類型適應症（尤其是狼瘡）中失敗的APO 或BAFF 化合物不同？我認為我們已經看到了許多挑戰。

And then just separately, on ligelizumab versus remibrutinib in CSU, can you just help us understand the decision points as it relates to ligelizumab for filing? And then how, if you do launch there, you'll trade off your expectations for remibrutinib in a similar setting?

然後，就 CSU 中的 ligelizumab 與 remibrutinib 單獨討論，您能否幫助我們了解與 ligelizumab 備案相關的決策點？然後，如果您確實在那裡推出，您將如何在類似的環境中權衡您對瑞布替尼的期望？

Yes. I think, John, are you still there? Do you want to take the ianalumab?

是的。我想，約翰，你還在嗎？你想服用ianalumab嗎？

Sure. Absolutely. And thanks for the question, Seamus. As we look at ianalumab, this is our anti-BAFF agent. And we really see 2 different modes of action with ianalumab. It's a direct lysis of B cells by ADCC as one path, and the other is BAFF receptor blockade that interrupts the BAFF-mediated signaling for B-cell maturation, proliferation and survival.

當然。絕對地。謝謝你的問題，Seamus。當我們查看 ianalumab 時，這是我們的抗 BAFF 劑。我們確實看到了 ianalumab 的 2 種不同的作用模式。一種是ADCC直接裂解B細胞，另一種是阻斷BAFF受體，阻斷BAFF介導的B細胞成熟、增殖和存活信號。

So the difference here is there are dual modes of mechanisms of action versus what has been seen with previous BAFF receptor blockers. And what we've seen is actually this counterbalance of the 2 mechanisms that allows us to see -- and we've actually seen good responses, as we said earlier, in our Phase II studies, and that's why we're moving forward in these various indications.

因此，這裡的區別在於，與以前的 BAFF 受體阻滯劑相比，有雙重作用機制模式。我們所看到的實際上是這兩種機制的平衡，使我們能夠看到——正如我們之前所說，在我們的 II 期研究中，我們實際上已經看到了良好的反應，這就是我們向前推進的原因這些各種跡象。

On your second question in terms of -- go ahead. Go ahead, Vas.

關於你的第二個問題——繼續。來吧，瓦斯。

I think -- I was just going to chime in on -- I think some of the competitor of historical molecules only targeted the BAFF ligand, and then only in certain subtypes of the BAFF ligand, so not completely comparable to previous results.

我想——我只是想插話——我認為歷史分子的一些競爭對手只針對 BAFF 配體，然後只針對 BAFF 配體的某些亞型，因此與以前的結果不完全可比。

Go ahead, John, on remibrutinib.

繼續，約翰，服用瑞布替尼。

Yes. So in terms of looking at remibrutinib versus ligelizumab. As we look at both combinations, we've seen good results in both. And as you know, for remibrutinib, for the BTK-selective oral inhibitor, what we've seen is also good results in CSU with an oral compound. So as we're moving forward, we're looking at both approaches, and we'll make decisions as we further analyze the results from ligelizumab. And then as we move forward with remibrutinib, we'll continue recruitment in these studies.

是的。因此，就瑞米布替尼與利格珠單抗的比較而言。當我們查看這兩種組合時，我們都看到了兩者的良好結果。如您所知，對於瑞布替尼，對於 BTK 選擇性口服抑製劑，我們所看到的在使用口服化合物的 CSU 中也取得了良好的效果。因此，在我們前進的過程中，我們正在研究這兩種方法，我們將在進一步分析 ligelizumab 的結果時做出決定。然後，隨著我們繼續使用瑞布替尼，我們將繼續在這些研究中進行招募。

I think, Seamus, the idea of ligelizumab, I guess the question, is there value in getting the medicine on the market ahead of the potential future launches in food allergy and CIndU? Or is that not a sensible strategic approach? And we just haven't come to a determination yet.

我認為，Seamus，ligelizumab 的想法，我想問題是，在食物過敏和 CIndU 的潛在未來推出之前將該藥物推向市場是否有價值？或者這不是一個明智的戰略方法？我們只是還沒有下定決心。

Our current view is that we -- with the superiority to placebo, it is potentially fileable. And of course, we'll review it with the FDA. So we're going to make those assessments carefully and then decide what the right approach is to take ahead.

我們目前的觀點是，我們 - 具有優於安慰劑的優勢，它可能是可歸檔的。當然，我們將與 FDA 一起審查它。因此，我們將仔細進行這些評估，然後決定採取什麼正確的方法。

Very good. So thanks, everyone, for joining today's conference call. We hope it was helpful to get a perspective on both the near term, but also the longer-term outlook of the company, the pipeline, the products and the things we're excited about. We're excited about delivering a strong 2022. And we'll look forward to keeping you up to date through various interactions, and then of course in our next quarterly conference call.

非常好。非常感謝大家參加今天的電話會議。我們希望對公司的近期和長期前景、管道、產品和我們感到興奮的事情有幫助。我們很高興能實現強勁的 2022 年。我們期待通過各種互動讓您了解最新情況，當然還有我們的下一個季度電話會議。

We wish you a great year, and we'll look forward to speaking to you soon. Thank you.

我們祝您有一個美好的一年，我們期待很快與您交談。謝謝你。

Thank you. That does conclude today's conference call. Thank you for participating. You may all disconnect.

謝謝你。這確實結束了今天的電話會議。感謝您的參與。你們都可以斷開連接。