Novartis AG (NVS) 2018 Q4 法說會逐字稿

Good morning and good afternoon. And welcome to the Novartis Q4 and Full Year 2018 Results Release Conference Call and Live Audio Webcast. (Operator Instructions) And the conference is being recorded. (Operator Instructions)

早上好，下午好。歡迎參加諾華第四季度和 2018 年全年業績發布電話會議和現場音頻網絡廣播。（操作員說明）會議正在錄製中。（操作員說明）

A recording of the conference call, including the Q&A session, will be available on our website shortly after the call ends. (Operator Instructions)

電話會議的錄音，包括問答環節，將在電話會議結束後不久發佈在我們的網站上。（操作員說明）

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

有了這個，我現在想把時間交給投資者關係全球主管 Samir Shah 先生。請繼續，先生。

Thank you very much. And good afternoon, everybody, and welcome to the webcast today.

非常感謝。大家下午好，歡迎收看今天的網絡直播。

Before we actually start, I would just like to read the safe harbor statement. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. Please refer to the company's Form 20-F on file with the U.S. Securities and Exchange Commission for a description of some of these factors.

在我們真正開始之前，我只想閱讀安全港聲明。今天提供的信息包含前瞻性陳述，涉及已知和未知的風險、不確定性和其他因素。這些可能導致實際結果與此類陳述明示或暗示的任何未來結果、業績或成就存在重大差異。請參閱公司在美國證券交易委員會備案的 20-F 表格，了解其中一些因素的說明。

Thank you. And with that, I'll hand the call to Vas Narasimhan.

謝謝。有了這個，我會把電話轉給 Vas Narasimhan。

Thank you, Samir, and thanks, everyone, for joining today's call. With me today in the room is Harry Kirsch, our CFO; Shannon Klinger, our General Counsel; John Tsai, our Chief Medical Officer and Head of Global Drug Development; David Endicott, our CEO of Alcon; Paul Hudson, our CEO of Pharma; Richard Francis, our CEO of Sandoz. And I'm proud to welcome Susanne Schaffert, our new CEO of Novartis Oncology.

謝謝薩米爾，也感謝大家參加今天的電話會議。今天和我一起在場的是我們的首席財務官 Harry Kirsch； Shannon Klinger，我們的總法律顧問； John Tsai，我們的首席醫療官兼全球藥物開發負責人；愛爾康首席執行官 David Endicott； Paul Hudson，我們的製藥公司首席執行官； Richard Francis，山德士的首席執行官。我很自豪地歡迎 Susanne Schaffert，我們諾華腫瘤部的新任首席執行官。

Susanne brings with her over 20 years of experience within the company, deep expertise within oncology. She most recently ran our radioligand therapy business post the transaction with AAA. And I have full confidence and really look forward to her great contributions running Oncology.

Susanne 帶來了她在公司超過 20 年的經驗，以及在腫瘤學方面的深厚專業知識。在與 AAA 交易後，她最近負責管理我們的放射配體治療業務。我有充分的信心，也非常期待她在運行腫瘤學方面做出巨大貢獻。

So if we move to Slide 5, through the pictures, you can see that in -- we really laid out, over the course of the last year, a clear aim to become a leading medicines company, powered by advanced therapy platforms and data science. There are 4 pillars to the transformation that we're currently undertaking: focusing the company; driving growth through cutting-edge platforms, which include continuing to drive our leading pipeline as well as building advanced therapy platforms; becoming more consistently passionate about productivity and margins; and building a new culture that will have a lasting impact on society. And over the course of today's presentation, I'll walk you through the progress we're making in every one of these dimensions.

因此，如果我們轉到幻燈片 5，通過圖片，您可以看到——在過去的一年裡，我們確實制定了一個明確的目標，即成為一家領先的醫藥公司，由先進的治療平台和數據科學提供支持.我們目前正在進行的轉型有 4 個支柱：專注於公司；通過尖端平台推動增長，包括繼續推動我們領先的管道以及構建先進的治療平台；對生產力和利潤率更加始終如一地充滿熱情；建立一種將對社會產生持久影響的新文化。在今天的演講過程中，我將向您介紹我們在這些方面的每一個方面所取得的進展。

But before doing that, I'd like to move to Slide 6, where you see our full year numbers, where we delivered strong growth with operating leverage in Q4 and in full year 2018. Harry will go through these numbers in more detail, but I think, most importantly, we've delivered against our guidance. We've delivered strong sales and core operating income growth, and we've delivered the operating leverage which we said we would to start us on a journey to getting to the mid-30s margin in Innovative Medicines. I'll speak more about that in a moment.

但在此之前，我想轉到幻燈片 6，您可以在其中看到我們的全年數據，我們在第四季度和 2018 年全年實現了強勁的運營槓桿增長。Harry 將更詳細地介紹這些數字，但我認為，最重要的是，我們已經違背了我們的指導方針。我們實現了強勁的銷售和核心營業收入增長，我們已經實現了我們所說的運營槓桿，我們將開啟我們在創新藥物領域達到 30 年代中期利潤率的旅程。稍後我會詳細說明這一點。

So moving to Slide 7. Over the course of this year, after assessing the longer-term history and the overall dynamics in the industry, we made a decision to focus Novartis as a leading medicines company. And we've taken principled actions over 2018 to make that a reality.

現在轉到幻燈片 7。在今年的過程中，在評估了該行業的長期歷史和整體動態之後，我們決定將諾華公司作為一家領先的藥品公司。我們在 2018 年採取了原則性行動來實現這一目標。

So if you go to Slide 8, you can see that we took a number of steps to exit -- exits to focus the company. These included, as you all well know, the GSK exit of the consumer JV, the planned sale of our U.S. oral solids business to Aurobindo, the sale of our Boston -- certain elements of our infectious disease portfolio to Boston Pharmaceuticals and importantly our planned spin of Alcon. We can talk more about that in the Q&A, but we are on track, as you saw from our full year earnings release, to make a proposal to our AGM at the end of February and then move towards a spin of Alcon in Q2, with an expectation to be able to do that in April, pending a number of steps that we still need to complete.

因此，如果你轉到幻燈片 8，你會看到我們採取了一些退出步驟——退出以專注於公司。眾所周知，其中包括 GSK 退出消費者合資企業、計劃將我們的美國口服固體業務出售給 Aurobindo、將我們的波士頓出售——我們將傳染病產品組合的某些元素出售給波士頓製藥公司，重要的是我們計劃愛爾康的旋轉。我們可以在問答中更多地討論這個問題，但正如您從我們的全年收益發布中看到的那樣，我們正在按計劃在 2 月底向我們的年度股東大會提出建議，然後在第二季度轉向愛爾康，期望能夠在四月份做到這一點，等待我們仍然需要完成的一些步驟。

We've also made a number of deals to build new platforms over the course of the year. Those include AveXis in gene therapy, along with the in-licensure of Spark in ophthalmology. We've also built out our cell therapy global manufacturing footprint, and Susanne will talk more about that in a moment, and also have built a new platform in radioligand therapy to tackle solid tumors. And again, Susanne will give us more details later on in the presentation.

在這一年中，我們還達成了許多交易來構建新平台。其中包括基因治療領域的 AveXis，以及眼科領域 Spark 的許可。我們還建立了我們的細胞療法全球製造足跡，Susanne 稍後會詳細討論這一點，並且還建立了一個新的放射配體療法平台來應對實體瘤。同樣，Susanne 將在稍後的演示中為我們提供更多詳細信息。

So moving to Slide 9. Along with the planned spin-off, I also wanted to highlight that Alcon continued to deliver solid performance through 2018. You can see on a full year sales basis, we continued to drive solid growth in a growing market. I think Alcon continues to demonstrate its power as a leader in both Vision Care as well as in surgical and as well as building a sustained pipeline of new innovations to build into those businesses. We also saw core margin expansion, as you see, between 2017 and 2018. And the Alcon leadership team, led by David Endicott, really an outstanding leadership team, remains confident that we will be able to, in the medium term, move those margins into the low to mid-20s.

所以轉到幻燈片 9。除了計劃中的分拆，我還想強調愛爾康在 2018 年繼續提供穩健的業績。你可以看到，在全年銷售的基礎上，我們繼續在不斷增長的市場中推動穩健增長。我認為愛爾康繼續展示其作為視力保健和外科領域領導者的實力，以及建立持續的新創新渠道以融入這些業務。如您所見，2017 年至 2018 年間，我們還看到了核心利潤率的擴張。由 David Endicott 領導的 Alcon 領導團隊，真的是一支非常出色的領導團隊，仍然相信我們能夠在中期將這些利潤率提高到 20 年代中期。

We had a Capital Markets Day in Q4 2018, and we plan further investor engagement in Q1 2019. As I mentioned, the vote at the AGM will happen on February 28. And the share ratio will be 5 Novartis shares to 1 Alcon share. You can find more information -- more detailed information in the shareholder brochure available online at the web address that you see on the slide.

我們在 2018 年第四季度舉辦了資本市場日，我們計劃在 2019 年第一季度進一步吸引投資者參與。正如我提到的，年度股東大會的投票將於 2 月 28 日進行。股份比例為5股諾華股份對1股愛爾康股份。您可以在幻燈片上看到的網址上在線找到更多信息——更詳細的信息。

Now moving to Slide 10 and on Sandoz. We've also undertaken a significant strategic pivot in Sandoz, where we're really trying to position Sandoz now from its position as the second-leading generic company in the world to a position where we can grow sustainably in the medium to long term. And there's 3 core elements of the transformation we're currently working on. One is even more heavily reshaping the portfolio towards biosimilars and hard-to-make generics. We had 2 new deals over the course of Q4 and in -- over the course of 2018: Biocon, an Indian manufacturer, to work on next-gen biosimilars; also, a deal with Gan & Lee to work on insulin biosimilars as well. Both will enable us to expand our pipeline of biosimilars in Sandoz.

現在轉到 Slide 10 和 Sandoz。我們還對 Sandoz 進行了重大的戰略調整，我們真的在努力將 Sandoz 從其目前作為世界第二大仿製藥公司的地位轉變為我們可以在中長期內實現可持續發展的地位。我們目前正在進行的轉型有 3 個核心要素。一個是更大幅度地重塑產品組合，轉向生物仿製藥和難以製造的仿製藥。我們在第四季度和 2018 年期間有 2 筆新交易：印度製造商 Biocon 致力於開發下一代生物仿製藥；此外，還與甘李公司就胰島素生物仿製藥的研究達成協議。兩者都將使我們能夠擴大我們在 Sandoz 的生物仿製藥管道。

We also continue to look at value-added medicine deals in an internal portfolio that we believe, over time, will enable us to strengthen our growth profile. We're also now looking at geographic focus. Even beyond the Aurobindo transaction, we'll be looking at other geographies where we may want to focus away from to enable us to really be positioned in markets where we can drive solid performance over the medium to long term.

我們還繼續關注內部投資組合中的增值醫藥交易，我們相信隨著時間的推移，這些交易將使我們能夠加強我們的增長前景。我們現在也在關注地理焦點。甚至在 Aurobindo 交易之外，我們還將關注我們可能希望關注的其他地區，以使我們能夠真正定位於我們可以在中長期內推動穩健業績的市場。

And lastly, we're leaning up the cost structure through SKU rationalization, a heavy focus on manufacturing footprint optimization. And also, the regional consolidation will support that. Taken together, over the next 18 months, we plan to make Sandoz an autonomous unit within Novartis to enable us to compete in what is an increasingly dynamic and challenging global generic environment.

最後，我們正在通過 SKU 合理化來傾斜成本結構，重點關注製造足跡優化。而且，區域整合將支持這一點。總之，在接下來的 18 個月裡，我們計劃讓 Sandoz 成為諾華內部的一個自治部門，使我們能夠在日益充滿活力和挑戰性的全球仿製藥環境中競爭。

So moving to Slide 11. I also wanted to highlight that we remain disciplined in shareholder focus and our capital allocation. This is something, as CEO coming into the role, I took very seriously to reflect hard on how we allocate capital and ensure we do it in a disciplined and consistent way. When you think about how we had invested in our organic businesses, the 100% tax-neutral spin-off of Alcon enables our shareholders to own a leading ophthalmology business, but also enables us as a company to focus our capital and our energy on building our core medicines business.

所以轉到幻燈片 11。我還想強調，我們在股東關注和資本配置方面仍然保持紀律。這是一件事情，作為 CEO 上任後，我非常認真地反思我們如何分配資本並確保我們以有紀律和一致的方式進行。當您想到我們如何投資有機業務時，Alcon 的 100% 稅收中性分拆使我們的股東能夠擁有領先的眼科業務，同時也使我們作為一家公司能夠將我們的資本和精力集中在建設上我們的核心藥品業務。

We continue to grow our dividend, and Harry will go over that in more detail. But for the 22nd consecutive year, we'll have a dividend increase. We're focusing on value-creating bolt-ons. Over the course of 2018, we did $15 billion in M&A bolt-on, and I see us continuing to want to do consistent M&A bolt-ons year-on-year. And lastly, we've had $17 billion of net share buybacks over the past 5 years, including a new $5 billion program. We'll continue to allocate capital to share buybacks when appropriate to increase the value per share for Novartis shareholders.

我們繼續增加股息，哈利將更詳細地討論這一點。但是連續第 22 年，我們將增加股息。我們專注於創造價值的補強。在 2018 年期間，我們進行了 150 億美元的併購補強，我認為我們繼續希望逐年進行一致的併購補強。最後，我們在過去 5 年中進行了 170 億美元的淨股票回購，其中包括一項新的 50 億美元計劃。我們將在適當的時候繼續分配資金進行股票回購，以增加諾華股東的每股價值。

So moving to Slide 12. When you look at the next pillar, it's really about driving that growth through cutting-edge platforms and cutting-edge innovation, ensuring that we build broad depth and breadth in our Innovative Medicines business.

所以轉到幻燈片 12。當你看下一個支柱時，它實際上是通過尖端平台和尖端創新推動增長，確保我們在創新藥物業務中建立廣泛的深度和廣度。

So when you go to Slide 13, you can see that the foundation for this will be our in-line brands, and we have very strong in-line brand performance over the course of 2018. COSENTYX continues to grow. In spite of multiple competitor entries and new competitor data, the COSENTYX momentum continues, and Paul will speak more about that. ENTRESTO is now a blockbuster, and we also feel good about ENTRESTO's long-term outlook. Paul will also mention a bit more about that.

所以當你轉到幻燈片 13 時，你會看到這將是我們的在線品牌的基礎，我們在 2018 年的在線品牌表現非常強勁。COSENTYX 繼續增長。儘管有多個競爭對手參賽和新的競爭對手數據，但 COSENTYX 的勢頭仍在繼續，保羅將更多地談到這一點。ENTRESTO 現在是一鳴驚人，我們也對 ENTRESTO 的長期前景感到樂觀。保羅也會更多地提到這一點。

Our Oncology portfolio, PROMACTA; Tafinlar + Mekinist; JAKAVI; and importantly Lutathera, which continues its strong performance, all give us confidence in these brands for the future in oncology. And even older brands such as XOLAIR continue to perform well with new indications that we added to the XOLAIR portfolio. Now both Kisqali and Kymriah have had slower starts, but we remain confident that with Kisqali, over time, we can build this into a blockbuster medicine with consistent effort and consistent focus on our new datasets. And with Kymriah, Susanne will mention more about where we are, but we feel confident, again, given our manufacturing expansion we have globally, we can drive Kymriah's growth well into the future.

我們的腫瘤產品組合 PROMACTA；他非拉 + 曲美替尼；賈卡維；重要的是，繼續保持強勁表現的 Lutathera 都讓我們對這些品牌在腫瘤學的未來充滿信心。甚至像 XOLAIR 這樣的老品牌也繼續表現良好，我們在 XOLAIR 產品組合中添加了新的適應症。現在 Kisqali 和 Kymriah 的起步都比較慢，但我們仍然相信，隨著時間的推移，有了 Kisqali，我們可以通過不懈的努力和對新數據集的持續關注，將其打造成為一鳴驚人的藥物。對於 Kymriah，Susanne 將更多地提及我們所處的位置，但我們再次充滿信心，鑑於我們在全球範圍內的製造擴張，我們可以推動 Kymriah 的未來發展。

So moving to Slide 14. Importantly also, we have 10 potential blockbuster launches planned over the next 2 years. We have 3 already launched in 2018 with Aimovig, Kymriah and Lutathera. We're on track for 4 more in 2019: BYL in advanced breast cancer; Mayzent, where we continue to have a solid regulatory review progress with FDA towards our action date later this year; RTH, we announced this morning that we will file shortly, plan to use our priority review voucher and continue to expect a launch in 2019; and Zolgensma in SMA Type 1, our breakthrough therapy for SMA with -- post the acquisition with AveXis.

所以轉到幻燈片 14。同樣重要的是，我們計劃在未來 2 年內推出 10 個潛在的重磅炸彈。我們已經在 2018 年推出了 3 款產品，包括 Aimovig、Kymriah 和 Lutathera。我們有望在 2019 年再獲得 4 個：BYL 治療晚期乳腺癌； Mayzent，我們在今年晚些時候的行動日期之前繼續與 FDA 取得穩固的監管審查進展； RTH，我們今天早上宣布我們將很快提交申請，計劃使用我們的優先審查憑證，並繼續期待在 2019 年推出；和 Zolgensma 在 SMA 類型 1 中，我們對 SMA 的突破性療法——在與 AveXis 的收購後。

So moving to Slide 15. We have a number of catalysts in 2019, important catalysts. I'd like to focus on the major late-stage readouts because these will be critical for us in terms of having the next wave of innovation to drive growth at the company. Zolgensma, our SMA Type 2 data package for the intrathecal formulation, will be presented at AAN in May. Fevipiprant, our first-in-class CRTh2 antagonist for eosinophilic asthma, will have its readout in the back half of the year, along with ENTRESTO HFpEF, ofatumumab, COSENTYX in non-radiographic axial SpA and our first PD-1 combination of PDR001 with TAFINLAR and MEKINIST in metastatic melanoma. So a busy year in terms of important readouts, along with, as you can see, many key approvals and major submissions.

所以轉到幻燈片 15。我們在 2019 年有許多催化劑，重要的催化劑。我想重點關注主要的後期數據，因為這些數據對我們進行下一波創新以推動公司增長至關重要。我們用於鞘內製劑的 SMA 2 型數據包 Zolgensma 將於 5 月在 AAN 上展示。Fevipiprant 是我們用於嗜酸性粒細胞性哮喘的一流 CRTh2 拮抗劑，將在今年下半年與 ENTRESTO HFpEF、ofatumumab、COSENTYX 一起用於非放射學軸性 SpA 以及我們的第一個 PD-1 組合 PDR001 和TAFINLAR 和 MEKINIST 在轉移性黑色素瘤中。因此，就重要讀數而言，這是忙碌的一年，正如您所看到的，還有許多關鍵批准和主要提交。

So moving to Slide 16. I also wanted to highlight where we're headed when we think longer term about the company. We are, of course, in 6 major therapeutic areas, and we want to be a diversified Innovative Medicines company. We want to have the diversification and offer investors the opportunity to invest in a company that covers a broad range of innovation across key therapeutic areas but also across key therapeutic platforms that will drive future growth.

所以轉到幻燈片 16。當我們從長遠考慮公司時，我還想強調我們的前進方向。當然，我們在 6 個主要治療領域，我們希望成為一家多元化的創新藥物公司。我們希望實現多元化，並為投資者提供機會，投資於一家涵蓋關鍵治療領域以及推動未來增長的關鍵治療平台的廣泛創新的公司。

In addition to small molecules and large molecules, which have underpinned our industry for decades, we want to be a leader in cell therapy, the reprogramming of cells to impact major diseases; gene therapy, where we have the opportunity to create definitive therapies for debilitating diseases; and radioligand therapy in oncology. And we think each one of these has the opportunity to provide new innovations across a broad range of the therapeutic areas that we're in, particularly the cell and gene therapies. So you can expect for us to continue to invest in these areas, continue to look out for bolt-on acquisitions in these spaces.

除了幾十年來一直支撐著我們行業的小分子和大分子外，我們還想成為細胞治療領域的領導者，細胞重新編程以影響重大疾病；基因療法，我們有機會為衰弱性疾病創造明確的療法；和腫瘤學中的放射配體治療。我們認為每一個都有機會在我們所處的廣泛治療領域提供新的創新，特別是細胞和基因療法。所以你可以期待我們繼續投資這些領域，繼續尋找這些領域的補強收購。

So going to Slide 17. I wanted to just take a moment to highlight the progress we've made post the AveXis acquisition. We now have 7 programs in the clinic over the next -- we expect to have 7 programs in the clinic over the next year across a range of indications, ophthalmology, hearing loss already in the clinic, as well as a range of other indications in neuroscience and a few that are undisclosed. And in parallel, Paul and the team are building out our manufacturing capacity so that we have ample capacity to enable us to manufacture these gene therapies for the world. We're not losing any time. We're continuing to build out our facilities in Chicago and North Carolina and in addition, looking for facilities outside the United States to ensure we have more than ample capacity for these launches.

轉到幻燈片 17。我想花點時間強調我們在收購 AveXis 後取得的進展。我們現在在接下來的診所裡有 7 個項目——我們預計明年在診所裡有 7 個項目，涵蓋一系列適應症、眼科、已經進入臨床的聽力損失，以及一系列其他適應症神經科學和一些未公開的。與此同時，保羅和團隊正在建設我們的製造能力，以便我們有足夠的能力為世界製造這些基因療法。我們不會失去任何時間。我們將繼續在芝加哥和北卡羅來納州建設我們的設施，此外，還在美國以外尋找設施，以確保我們有足夠的能力進行這些發射。

So moving to Slide 18. Now I know one of the narratives about Novartis is we've never delivered on our productivity and never delivered on the margin expansion. And I think what you have now is a leadership team that's deeply committed to it, that believes that the possibilities are there and is determined to show, through principled actions consistent over time, that we drive that productivity and margin expansion.

所以轉到幻燈片 18。現在我知道關於諾華的一個說法是我們從未交付過我們的生產力，也從未交付過利潤擴張。而且我認為你現在擁有的是一個深深致力於它的領導團隊，他們相信可能性是存在的，並且決心通過長期一致的原則行動來表明我們推動了生產力和利潤率的增長。

On Slide 19, I'll just reiterate what I showed all of you earlier last year, which is our commitment to get to the mid-30s with our Innovative Medicines business in terms of our margins and to do so not only with accelerating our growth drivers but through clear productivity programs that makes the company more efficient and fit for the future.

在幻燈片 19 上，我將重申去年早些時候我向大家展示的內容，即我們承諾將我們的創新藥物業務的利潤率提高到 30 年代中期，這樣做不僅要加速我們的增長驅動力，而是通過明確的生產力計劃使公司更有效率並適應未來。

So when you go to Slide 20, I wanted to just take a moment and highlight where we are on that productivity agenda. First, in manufacturing and NTO, over the course of last year, we announced 16 plant transformations, including 8 plant exits. I think it's one of the most -- in Novartis' history, the biggest move -- biggest set of moves we've made on our manufacturing footprint, including a significant restructuring in Switzerland. And we're also working to deploy technology to reduce our inventory level and improve our overall efficiency in manufacturing.

所以當你轉到幻燈片 20 時，我想花點時間強調一下我們在生產力議程上的位置。首先，在製造和 NTO 方面，在去年的過程中，我們宣布了 16 個工廠轉型，其中包括 8 個工廠退出。我認為這是諾華歷史上最多的——最大的舉措之一——我們在製造足跡上採取的最大舉措之一，包括在瑞士的重大重組。我們還致力於部署技術以降低我們的庫存水平並提高我們的整體製造效率。

In Novartis Business Services, we're driving a lot of work through standardization and automation. But we also announced global restructuring plans to build out further our 5 Novartis global service centers to enable us to have a cost-effective footprint and also to speed up the automation in some of our core business service areas. And lastly, we brought on procurement executives from outside of the pharmaceutical industry, including from consumer packaged goods, to lead -- and retail, to lead some of the functions within procurement to really drive a renewed effort to tackle the $16 billion we have in external spend at the company. Taken together, we've set ourselves a goal of $2 billion of savings by 2020, some -- much of which we hope to flow to the bottom line, along with funding our investments and upcoming launches. I also want to highlight we're going to increase our focus on our cash conversion cycle to really ensure we can generate strong free cash flow consistently over time.

在 Novartis Business Services，我們通過標準化和自動化推動了大量工作。但我們還宣布了全球重組計劃，以進一步建設我們的 5 個諾華全球服務中心，使我們能夠擁有具有成本效益的足跡，並加快我們一些核心業務服務領域的自動化。最後，我們聘請了來自製藥行業以外的採購主管，包括來自包裝消費品的採購主管和零售主管，以領導採購中的一些職能，真正推動新的努力來解決我們在全球範圍內擁有的 160 億美元公司的外部支出。總而言之，我們為自己設定了到 2020 年節省 20 億美元的目標，其中一些——我們希望其中大部分能夠用於盈利，同時為我們的投資和即將推出的產品提供資金。我還想強調，我們將更加關注我們的現金轉換週期，以真正確保我們能夠隨著時間的推移持續產生強勁的自由現金流。

So moving to Slide 21. I wanted to just say a word. We continue to advance our enterprise-wide digital transformation. This will, I believe, become a significant pillar for the company in order to help us become much more efficient but also help us in drug discovery, help our sales forces work more efficiently, as well as help our manufacturing and development trial operations. There's a lot on this slide, but I think -- I hope it gives you a sense of the scale and breadth of our efforts in terms of our digital transformation. We have a dedicated organization that's working tirelessly right now to make each one of these projects a reality.

所以轉到幻燈片 21。我只想說一句話。我們繼續推進整個企業的數字化轉型。我相信，這將成為公司的重要支柱，以幫助我們提高效率，同時幫助我們進行藥物發現，幫助我們的銷售人員更有效地工作，以及幫助我們的製造和開發試驗運營。這張幻燈片上有很多內容，但我認為 - 我希望它能讓您了解我們在數字化轉型方面所做努力的規模和廣度。我們有一個專門的組織，現在正在不知疲倦地工作，以實現這些項目中的每一個。

So moving to Slide 22. I just wanted to briefly close by mentioning a bit about where we are in our culture transformation and where we are on our transformation in building trust with society. So on Slide 23, we continue our journey to transform the culture of Novartis into an inspired, curious, unbossed company, a much more empowered organization. I've spoken to many investors about this over the recent year. We believe, in the long run, this will enable us to be the kind of company that can bring breakthrough innovations forward and deploy those innovations to patients efficiently, effectively and with maximum impact. We reshaped our executive committee. We're focused heavily on upscaling our leadership capabilities at all levels of the company. I believe this -- it's something our entire leadership team is focused on, and we'll be able to show, I hope, tangible progress over the coming years.

所以轉到幻燈片 22。最後，我想簡單地提一下我們在文化轉型中所處的位置，以及我們在與社會建立信任方面的轉型中所處的位置。因此，在幻燈片 23 上，我們繼續我們的旅程，將諾華的文化轉變為一家充滿靈感、充滿好奇心、沒有領導的公司，一個更有權力的組織。近年來，我與許多投資者談過這個問題。我們相信，從長遠來看，這將使我們成為能夠帶來突破性創新並將這些創新高效、有效和最大影響地部署到患者身上的公司。我們重組了執行委員會。我們非常注重提升公司各個層級的領導能力。我相信這一點——這是我們整個領導團隊都關注的事情，我希望我們能夠在未來幾年取得切實進展。

And on Slide 24, we've renewed our commitment to build lasting trust with society. Whether that's the ethical standards we take in terms of how we behave in every market that we operate in; our approach to pricing and access and global access to medicine; taking on global health challenges where we make clear principled commitments; corporate citizenship where we've committed on clear environmental goals, human rights goals and as well as goals on diversity; and in how we engage stakeholders around the world. I would want all of our investor community to know we're very committed to this and committed to being a company that shows we're about doing the right things for society as well as the right things for our business.

在幻燈片 24 上，我們重申了與社會建立持久信任的承諾。這是否是我們在我們經營的每個市場中的行為方式所採用的道德標準；我們的定價和獲取方法以及全球獲取藥物的方法；應對全球衛生挑戰，我們做出明確的原則性承諾；企業公民，我們致力於明確的環境目標、人權目標以及多樣性目標；以及我們如何讓世界各地的利益相關者參與進來。我希望我們所有的投資者社區都知道我們非常致力於此，並致力於成為一家表明我們正在為社會做正確的事情以及為我們的業務做正確的事情的公司。

So moving to Slide 25. Just to take it all together, we're well positioned for top and bottom line growth. We have strong in-market growth drivers with 15 in-market blockbusters, 10 potential blockbusters expected to launch in the coming years, a clear savings program. And while we do have patent expiries coming over this period of time, we feel confident that we can grow top and bottom line through this period.

所以轉到幻燈片 25。綜上所述，我們已經做好了頂線和底線增長的準備。我們擁有強大的市場增長動力，包括 15 款市場大片、10 款有望在未來幾年推出的潛在大片，以及一項明確的儲蓄計劃。雖然我們確實有專利在這段時間內到期，但我們相信我們可以在這段時間內增加收入和利潤。

So if you go to the next slide, I'll hand it over to Harry for an update on the financials. Harry?

所以如果你轉到下一張幻燈片，我會把它交給 Harry，讓他了解最新的財務狀況。哈利？

Yes. Thank you, Vas. Good morning, good afternoon, everybody. As usual, my comments will refer to growth rates in constant currencies, unless I say otherwise.

是的。謝謝你，瓦斯。大家早上好，下午好。像往常一樣，除非我另有說明，否則我的評論將參考固定貨幣的增長率。

So on Slide 27, just a quick comparison between the guidance we gave in January last year and the final results. As you can see, we came in exactly on guidance and even a bit at the upper end of -- for sales.

因此，在幻燈片 27 上，我們對去年 1 月給出的指導與最終結果進行了快速比較。如您所見，我們完全按照指導進行了銷售，甚至在銷售的上端也有一點。

Slide 28 shows the summary of our quarter 4 and full year performance. We continued to deliver strong growth in quarter 4 with sales increasing 6%, driving core operating income up 11%. Full year sales up 5%, mainly driven by COSENTYX, AAA and our 4 new additional blockbusters, including ENTRESTO. The sales growth and gross margin expansion drove full year core operating income up 8%.

幻燈片 28 顯示了我們第 4 季度和全年業績的總結。我們在第 4 季度繼續實現強勁增長，銷售額增長 6%，推動核心營業收入增長 11%。全年銷售額增長 5%，主要受 COSENTYX、AAA 和我們的 4 個新的重磅炸彈的推動，包括 ENTRESTO。銷售增長和毛利率擴張推動全年核心營業收入增長 8%。

Operating income declined in both quarter 4 and full year. This was mainly due to M&A transactions, higher restructuring costs for productivity programs and impairment charges. Full year net income increased 64% to $12.6 billion, driven by the gains from the OTC joint venture stake exit in quarter 2 of 2018. Free cash flow grew 12% during 2018 to $11.7 billion. And I'll come back to free cash flow shortly.

第 4 季度和全年的營業收入均有所下降。這主要是由於併購交易、提高生產力計劃的重組成本和減值費用。受 2018 年第二季度 OTC 合資企業股權退出收益的推動，全年淨收入增長 64% 至 126 億美元。2018 年自由現金流增長 12% 至 117 億美元。我很快就會回到自由現金流。

One of our key priorities, as you know, is operational excellence, and of course, this includes margin expansion. And we have delivered on that priority in 2018. So on Slide 29, you see the quarter 4 and full year core margins of the group and each division. Strong sales uptake in Innovative Medicines drove margin expansion up 100 basis points for the year to 32% of sales, on its way to the mid-30s margin goal by 2022. Sandoz had margin at 20% level, despite U.S. pricing pressures, due to gross margin improvements. And Alcon full year margin grew to 18%, mainly driven by higher sales and improved gross margin. So the total group margins improved by 70 basis points for the full year to 26.6% of sales.

如您所知，我們的主要優先事項之一是卓越運營，當然，這包括擴大利潤。我們已在 2018 年實現了這一優先事項。因此，在幻燈片 29 上，您可以看到該集團和每個部門的第 4 季度和全年核心利潤率。創新藥物的強勁銷售推動全年利潤率增長 100 個基點，達到銷售額的 32%，到 2022 年實現 30 年代中期的利潤率目標。儘管美國定價壓力很大，但由於毛利率提高，Sandoz 的利潤率仍保持在 20% 的水平。愛爾康全年利潤率增長至 18%，主要受銷售額增加和毛利率提高的推動。因此，全年集團總利潤率提高了 70 個基點，達到銷售額的 26.6%。

Slide 30 shows the strong free cash flow progression over the last 2 years, growing from $9.5 billion in 2016 to $11.7 billion in 2018. In 2018, the performance was mainly driven by higher cash flows from operations, underpinned by the improved core operating income. As you can expect, we will continue to place a strong focus on cash flow management.

幻燈片 30 顯示了過去兩年自由現金流的強勁增長，從 2016 年的 95 億美元增長到 2018 年的 117 億美元。2018 年，業績主要受核心營業收入改善支撐的運營現金流量增加所推動。如您所料，我們將繼續高度重視現金流管理。

Strong operating cash flow allows us to execute well on our capital allocation strategy, as Vas mentioned before. This includes paying a strong and growing dividend in Swiss francs. As you see on Slide 31, we are proposing the 22nd dividend increase to CHF 2.85 per share, an increase of 2%. This represents a 3% dividend yield and a payout ratio of 57% of free cash flow.

正如 Vas 之前提到的，強勁的經營現金流使我們能夠很好地執行我們的資本配置策略。這包括以瑞士法郎支付強勁且不斷增長的股息。正如您在幻燈片 31 中所見，我們提議將第 22 次股息增加至每股 2.85 瑞士法郎，增幅為 2%。這代表 3% 的股息收益率和 57% 的自由現金流的派息率。

On Slide 32, you see our 2019 full year guidance. As Vas highlighted, we are making a number of changes to focus the company. We know it will be quite complex to model our company results for 2019, so I hope the following information is helpful as forecast assumptions. We expect the Alcon spin to take place in quarter 2, and we expect the Sandoz-Aurobindo deal to close during 2019. A reasonable forecast assumption for that would be in quarter 3. However, exact dates for these 2 events are not certain, so we are providing guidance on both the current group structure and the new focused company.

在幻燈片 32 上，您可以看到我們的 2019 年全年指南。正如 Vas 強調的那樣，我們正在進行一些改變以集中公司的注意力。我們知道，為我們公司 2019 年的業績建模會非常複雜，因此我希望以下信息有助於作為預測假設。我們預計 Alcon 分拆將在第二季度進行，我們預計 Sandoz-Aurobindo 交易將在 2019 年完成。一個合理的預測假設是在第 3 季度。但是，這兩個事件的確切日期不確定，因此我們正在為當前的集團結構和新的重點公司提供指導。

To keep the presentation a bit short, I will comment on our new focused medicines company guidance. Here, we exclude Alcon and the Sandoz U.S. dermatology and oral solids portfolio for the full year in both 2018 and '19. Sales for the new focused medicines company are expected to grow mid-single digit. By division, Innovative Medicines sales are expected to grow mid-single digit and drive, of course, new focused company.

為了使演講簡短一些，我將評論我們新的重點藥品公司指南。在這裡，我們排除了 2018 年和 19 年全年的 Alcon 和 Sandoz 美國皮膚病學和口腔固體產品組合。新的重點藥品公司的銷售額預計將增長中等個位數。按部門劃分，創新藥物的銷售額預計將增長中等個位數，當然還會推動新的重點公司。

Sales growth. Sandoz sales are expected to be broadly in line with prior year. Core operating income is expected to grow ahead of sales, mid- to high-single digit. Overall, we expect 2019 to be another year of good sales growth and margin expansion for the company.

銷售增長。Sandoz 的銷售額預計與上年大致持平。預計核心營業收入增長將超過銷售額，達到中高個位數。總體而言，我們預計 2019 年將是公司銷售增長和利潤率增長良好的又一年。

In addition to the full year guidance, I wanted to comment on expected quarter 1 core operating income dynamics. We expect core operating income growth for the current group structure to be low to mid-single digits in quarter 1. This is due to quarter 1 including the impact from prelaunch investments, mainly for Zolgensma and other key launch products.

除了全年指導外，我還想評論一下預期的第一季度核心營業收入動態。我們預計當前集團結構的核心營業收入增長在第一季度將處於中低個位數。這是由於第一季度包括上市前投資的影響，主要針對 Zolgensma 和其他主要上市產品。

Sales contribution is expected in the future quarters for those. As a reminder, quarter 1 '19 will compare against the last quarter of income from the OTC joint venture recorded in associates' companies in quarter 1 2018.

預計未來幾個季度的銷售貢獻。提醒一下，19 年第一季度將與 2018 年第一季度聯營公司記錄的場外交易合資企業收入的最後一個季度進行比較。

On Slide 33, I would like to add some perspective on other key elements of our expected bottom line performance in 2019 beyond core operating income.

在幻燈片 33 上，我想補充一些關於我們 2019 年預期底線業績的其他關鍵要素的觀點，超出核心營業收入。

For the new focused company, we expect core net financial expenses to be broadly in line with 2018 net financial expenses for the current group structure. On core taxes, we expect the full year rate to increase slightly from 15.7% in 2018 to around 16% in 2019. This is mainly due to the mathematical effect from the loss of income from the OTC joint venture. To assist your modeling, we will provide you also with pro forma numbers at the first earnings release after the recommended Alcon spin.

對於新的重點公司，我們預計核心淨財務費用將與當前集團結構的 2018 年淨財務費用大致一致。在核心稅收方面，我們預計全年稅率將從 2018 年的 15.7% 小幅上升至 2019 年的 16% 左右。這主要是由於 OTC 合資企業收入損失的數學效應。為了幫助您建模，我們還將在建議的愛爾康分拆後的第一個收益發佈時為您提供預估數字。

On Slide 34, you see how currencies would impact our results if late January rates prevail for the remainder of 2019. Due to the stronger U.S. dollar against most currencies, the full year impact on sales would be negative 2%; on core operating income, negative 3%. For quarter 1, the currency impact would be higher as the U.S. dollar strengthened throughout the year last year. The negative effect on sales would be, in quarter 1, 5% and negative 7% on core operating income. As you know, the expected currency impact is updated on our website monthly.

在幻燈片 34 上，您可以看到如果 2019 年剩餘時間採用 1 月下旬的利率，貨幣將如何影響我們的結果。由於美元兌大多數貨幣走強，全年對銷售額的影響將為負 2%；核心營業收入為負 3%。對於第一季度，由於美元去年全年走強，貨幣影響會更大。對銷售的負面影響將在第一季度對核心營業收入產生 5% 和 7% 的負面影響。如您所知，預期的貨幣影響每月都會在我們的網站上更新。

And with that, I hand over to Paul.

然後，我交給保羅。

So thank you, Harry. Maybe we could start with COSENTYX.

所以謝謝你，哈利。也許我們可以從 COSENTYX 開始。

It's been a very impressive 2018, strong growth driven by demand and well positioned across all indications. The year played out pretty much as we predicted in terms of our performance in market share and our growth across the world. I think we have to -- a shout-out for our continued superb growth in the U.S., 29% in TRx in dermatology, close to 50% in rheumatology. So we're really the market leader in the new entrants, defining what will be the future era in immunology in and around these diseases. We've gained share, and we've consolidated our position.

2018 年令人印象深刻，在需求的推動下實現了強勁增長，並且在所有指標上都處於有利地位。就我們在市場份額和全球增長方面的表現而言，這一年的表現與我們預測的差不多。我認為我們必須——大聲疾呼我們在美國的持續高速增長，皮膚病學 TRx 增長 29%，風濕病學增長接近 50%。因此，我們確實是新進入者的市場領導者，定義了這些疾病及其周圍免疫學的未來時代。我們獲得了份額，鞏固了我們的地位。

We've also finessed our access for 2019, much like we predicted last year. We want to make sure that we're available in the first-line setting. We want to make sure that those who need the medicine most can get it. But I think it's really worth being clear, as we go into Q1, our expectation. Our expectation is growth quarter-on-quarter, year-over-year. Our expectation is strong performance year-over-year, 29 (sic) [2019] over 2018. Yes, we have verification, copay resets and other nuances in Q1, but we expect to repeat our successes in terms of increasing demand, as we saw in 2018.

我們還優化了 2019 年的訪問權限，就像我們去年預測的那樣。我們要確保我們在一線設置中可用。我們要確保那些最需要藥物的人能夠得到它。但我認為，當我們進入第一季度時，我們的預期確實值得明確。我們的預期是環比增長，同比增長。我們的預期是同比表現強勁，29 (sic) [2019] 超過 2018 年。是的，我們在第一季度有驗證、共付額重置和其他細微差別，但我們希望在增加需求方面重複我們的成功，就像我們在 2018 年看到的那樣。

We didn't stop there, of course. We have a lot of work to do. And we embarked on the ARROW study, a study designed to advance understanding in dermatology and not just to seek a marketing message. It is a study that is set out to try and help understand the extra manifestations, and difficult-to-treat patients are more prevalent than you realize. And we'll probably be one of the largest groups overall in the disease area. As we say, it takes more than clear skin to win in this area.

當然，我們並沒有就此止步。我們有很多工作要做。我們開始了 ARROW 研究，該研究旨在促進對皮膚病學的理解，而不僅僅是尋求營銷信息。這項研究旨在嘗試幫助理解額外的表現，而難以治療的患者比您意識到的更為普遍。我們可能會成為疾病領域最大的群體之一。正如我們所說，要想在這一領域取勝，光靠皮膚白淨是不夠的。

And then finally, in terms of news flow, PREVENT will read out. The non-radiographic axial SpA population is significant as a stand-alone, but I think it will add to the weight of the data about why COSENTYX is strongly positioned to be one of the winners as we go forward in 2019 and beyond.

最後，就新聞流而言，將宣讀 PREVENT。非放射線軸向 SpA 人口作為一個獨立的群體是重要的，但我認為這將增加數據的權重，說明為什麼 COSENTYX 在我們 2019 年及以後的前進中有能力成為贏家之一。

As we turn to ENTRESTO, it gives me a lot of personal pride and on behalf of the team involved to say that we reached blockbuster status. Whilst it's incredibly important for ENTRESTO and we go into our -- contribute heavily to our margin expansion story going forward, I think it also is a marker for our ability to execute. For 2019, we see launches coming. Our ability to compete hands down in competitive markets like immunology, but our ability to build an established market and go on and reset what standard of care is are critical skills as we go into this unprecedented period of launches.

當我們轉向 ENTRESTO 時，它給了我很多個人自豪感，並代表相關團隊說我們達到了重磅炸彈的地位。雖然這對 ENTRESTO 來說非常重要，而且我們為我們未來的利潤擴張故事做出了重大貢獻，但我認為這也是我們執行能力的標誌。對於 2019 年，我們看到發布即將到來。我們在免疫學等競爭激烈的市場中的競爭能力毋庸置疑，但我們建立一個既定市場並繼續和重新設定護理標準的能力是我們進入這個前所未有的發佈時期的關鍵技能。

So we're delighted with approximately -- just over, in fact, 100% growth 2018 over 2017. Particularly pleased with Q4. And as we go into the year, we'll guide you to think about Q2 and Q4 this year. That's historically where we've seen the major growth. And we're excited about what that could mean, again, to add to the overall performance of Novartis.

所以我們很高興大約 - 事實上，2018 年比 2017 年增長了 100%。對第四季度特別滿意。隨著我們進入這一年，我們將引導您思考今年的第二季度和第四季度。從歷史上看，這是我們看到主要增長的地方。我們對這可能意味著什麼感到興奮，再次增加諾華的整體業績。

Now everybody is sort of excited and waiting for PARAGON. And whilst we are too, the data readout will be a bit later this year.

現在每個人都有些興奮，都在等待 PARAGON。雖然我們也是，但數據讀出將在今年晚些時候進行。

It would be remiss not to mention PIONEER. PIONEER is a definitive bit of work the team did out of the U.S., which really looks at patients who initiated with drug in the acute setting and what you can do in terms of reducing overall readmission, a significant area of priority for health systems across the world, not least in the U.S.

更不用說 PIONEER 了。PIONEER 是團隊在美國以外所做的一項決定性工作，它真正關注在急性環境中開始使用藥物的患者，以及在減少整體再入院方面可以做些什麼，這是整個衛生系統的一個重要優先領域世界，尤其是在美國

The type of performance of ENTRESTO in the PIONEER study is a real marker in the sand to show what's possible. We have seen, although it's going to take some time to update treatment protocols and do different things, as we know, across the world, there are 1 or 2 countries where the performance has changed dramatically and quickly in the acute setting.

PIONEER 研究中 ENTRESTO 的性能類型是一個真實的標記，可以顯示什麼是可能的。我們已經看到，雖然更新治療方案和做不同的事情需要一些時間，但正如我們所知，在世界範圍內，有 1 或 2 個國家在急性環境中的表現發生了巨大而迅速的變化。

Just to give you some indication of what that's worth. As we got close to the end of '18, we had over 280,000 patients currently on treatment with ENTRESTO. The acute setting opportunity, there are over 300,000 opportunities to prescribe a new medicine in that setting annually also. So we know it's a big opportunity. We're well positioned. We're excited about what this means, continued strong news flow and our desire to push on and hopefully get good PARAGON data, too.

只是為了讓你知道它的價值。當我們接近 18 年底時，我們目前有超過 280,000 名患者正在接受 ENTRESTO 治療。急性環境機會，每年也有超過 300,000 次機會在這種情況下開出新藥。所以我們知道這是一個很大的機會。我們的位置很好。我們對這意味著什麼感到興奮，持續強勁的新聞流以及我們繼續前進並希望獲得良好 PARAGON 數據的願望。

Looking ahead to the new launches. It's fantastic for myself, for the team to have 3 really groundbreaking opportunities in 2019, stood on the shoulders of great execution across the board in '18. We will enter secondary progressive MS this year, and this is Mayzent. Sulfonamide is the only medicine that is proven to work in this patient population. To remind you that 50% to 80% of secondary -- of patients with MS will move on through the secondary progressive MS transition.

期待新的發布。這對我自己來說太棒了，對於球隊來說，在 2019 年有 3 個真正具有開創性的機會，站在 18 年全面執行力的肩膀上。今年我們將進入二級進展型 MS，這就是 Mayzent。磺胺類藥物是唯一被證明對這類患者有效的藥物。提醒您，50% 到 80% 的繼發性多發性硬化症患者將繼續經歷繼發性進展性多發性硬化症過渡期。

Why is it important? It's important because they need a real treatment as an option. It's important because, as we enter our regulatory conversations, we can properly characterize for the physician and the patient how we described our patient in the label. And indeed, for the payer and those in charge of reimbursement, they can make sure the patient is covered in terms of their own health system. So we look forward to bringing that to market in the early part of this year.

它為什麼如此重要？這很重要，因為他們需要真正的治療作為一種選擇。這很重要，因為當我們進入我們的監管對話時，我們可以為醫生和患者正確描述我們如何在標籤中描述我們的患者。事實上，對於付款人和負責報銷的人來說，他們可以確保病人在他們自己的醫療系統範圍內。因此，我們期待在今年年初將其推向市場。

For Zolgensma, the excitement of course is clearly building on the launch in the first half of this year. I think it's also worth reiterating that we haven't finalized a price, and we haven't communicated therefore a price, but there are some points of reference out there in the market. And the draft [NICE] report against current best standard of care shows that Zolgensma would be cost-effective up to $5 million. Now again, we haven't reached a conclusion on what we should price it at, but I can assure you that constructive conversations both with regulators and payers have brought us to a position where we feel we will be able to deliver on the scientific and clinical promise and find the best way, either through the price or the ability to pay over a period of time, to give the patients the best possible access.

對於 Zolgensma 來說，興奮當然是建立在今年上半年的發布之上。我認為還值得重申的是，我們還沒有最終確定價格，因此我們還沒有就價格進行溝通，但市場上有一些參考點。根據當前最佳護理標準的 [NICE] 報告草案顯示，Zolgensma 的成本效益高達 500 萬美元。再一次，我們還沒有就我們應該定價多少達成結論，但我可以向你保證，與監管機構和付款人的建設性對話使我們處於一個位置，我們認為我們將能夠實現科學和臨床承諾並找到最好的方法，無論是通過價格還是在一段時間內的支付能力，為患者提供最好的途徑。

In terms of news flow, I'm excited about SMA 2 and the strong data in intrathecal. We're having the conversations with the regulators, John may touch on that, about how broad our label is. But again, everything has been incredibly constructive.

在新聞流方面，我對 SMA 2 和鞘內的強大數據感到興奮。我們正在與監管機構進行對話，約翰可能會談到我們的標籤有多廣泛。但同樣，一切都具有令人難以置信的建設性。

As you may have picked up, this morning in RTH, brolucizumab, there is -- we paid the voucher to make sure that we enter the market before the end of 2019. And although we will only submit in the next few days or a week or so, we feel very confident in our position to be in market before the end of the year. And the last year or so, for me personally, becoming more adept or expert in this area, the HAWK and HARRIER data and our opportunity to dry better and the overall superiority in key secondary endpoints has led us to a point where we know we're probably going to have unmatched benefit both for physician and in terms of their ability to dry the retina and for the patient in terms of fewer injections without compromising on the quality of the vision and expectation.

正如你可能已經註意到的那樣，今天早上在 RTH，brolucizumab，我們支付了代金券以確保我們在 2019 年底之前進入市場。雖然我們只會在接下來的幾天或一周左右提交，但我們對我們在年底前進入市場的地位充滿信心。就我個人而言，在過去一年左右的時間裡，HAWK 和 HARRIER 數據以及我們更好地干燥的機會以及關鍵次要終點的整體優勢使我們達到了我們知道我們的地步就醫生和他們乾燥視網膜的能力而言，以及在不影響視力和期望質量的情況下減少注射次數方面，這可能會給醫生帶來無與倫比的好處。

So overall, fantastic COSENTYX and ENTRESTO. Good work. Well done. But more importantly, we have to pull that forward into the launches, and we're really excited about what's ahead. Susanne?

總的來說，很棒的 COSENTYX 和 ENTRESTO。幹得好。做得好。但更重要的是，我們必須將其推進到發布中，我們對未來的發展感到非常興奮。蘇珊娜？

Thank you, Paul. So actually, on Slide 40, you see that Oncology had a very good year in 2018. We were growing 9%, driven by very strong performance of our growth drivers.

謝謝你，保羅。所以實際上，在幻燈片 40 上，您會看到腫瘤科在 2018 年表現非常好。在我們的增長動力非常強勁的表現推動下，我們增長了 9%。

And as Vas already mentioned, both PROMACTA and Tafinlar + Mekinist were both growing over 30%, both reaching blockbuster status, and we are very confident that these 2 therapies will continue to be clear market leaders in their classes. We are also excited to see data on the combination of Tafinlar + Mekinist with our PD-1 inhibitor later this year. One maybe to mention also is JAKAVI, they have continued with strong double-digit growth and almost made it to blockbuster.

正如 Vas 已經提到的，PROMACTA 和 Tafinlar + Mekinist 都增長了 30% 以上，都達到了重磅炸彈的地位，我們非常有信心這兩種療法將繼續成為同類產品中明顯的市場領導者。我們也很高興在今年晚些時候看到有關 Tafinlar + Mekinist 與我們的 PD-1 抑製劑聯合用藥的數據。值得一提的還有 JAKAVI，他們繼續保持兩位數的強勁增長，幾乎一鳴驚人。

So going to the next slide. I think Vas clearly mentioned that our aim is to build leadership in advanced therapy platforms, and one is clearly our radioligand therapy platform. We are very excited about the performance.

轉到下一張幻燈片。我認為 Vas 明確提到我們的目標是在先進的治療平台中建立領導地位，其中一個顯然是我們的放射配體治療平台。我們對錶演感到非常興奮。

Lutathera continues to exceed our expectations, having reached sales of $160 million in the first year of launch in 2018. We see continued strong launch uptake in the U.S. By now, we have over 100 centers actively prescribing and over 80% of lives covered. We also saw good progress in Europe with the reimbursement. In the U.K., we already have 19 prescribing centers.

Lutathera 繼續超出我們的預期，在 2018 年推出的第一年就達到了 1.6 億美元的銷售額。我們看到在美國持續強勁的發射吸收。到目前為止，我們有超過 100 個中心積極開處方，覆蓋了超過 80% 的生命。我們還看到歐洲在報銷方面取得了良好進展。在英國，我們已經有 19 個處方中心。

It's important to remember that radioligand platform requires managing a highly complex supply chain, from securing a reliable isotope, overcomplex manufacturing steps and shipping with no room for delays, given the very short half-life of the product of only 3 days. We are very proud in AAA that we have vertical integration and really, this resulting in a very high reliability of success, enabling us to deliver the product within 2 weeks from taking the order. We believe this gives us a unique differentiated advantage in a growing transformative space that is difficult to replicate.

重要的是要記住，放射性配體平台需要管理一個高度複雜的供應鏈，從確保可靠的同位素、過於復雜的製造步驟和沒有延遲餘地的運輸，考慮到產品的半衰期非常短，只有 3 天。我們對 AAA 感到非常自豪，因為我們擁有垂直整合，實際上，這導致了非常高的成功可靠性，使我們能夠在接到訂單後的 2 週內交付產品。我們相信，這為我們在不斷增長的難以復制的變革空間中提供了獨特的差異化優勢。

When you move to Slide 42, you see the pipeline that we have built on our radioligand platform. And we are very excited about the potential breadth of this platform across a number of solid tumor types. As you see, we already could build a broad pipeline and have several interesting compounds starting development in 2018.

當您轉到幻燈片 42 時，您會看到我們在我們的放射性配體平台上構建的管道。我們對該平台在多種實體瘤類型中的潛在應用範圍感到非常興奮。如您所見，我們已經可以建立廣泛的管道，並在 2018 年開始開發幾種有趣的化合物。

As you're familiar with, we closed the Endocyte acquisition in Q4, and that gives us access to lead product PSMA-617, which is a radioligand therapy with the potential to be a first-in-class asset in prostate cancer, which is obviously a much larger indication than neuroendocrine tumors. So Phase III trial is underway. We will focus on enrolling this trial quickly, and we look forward to data readout and filing in 2020.

如您所知，我們在第四季度完成了對內細胞的收購，這使我們能夠獲得主導產品 PSMA-617，這是一種放射配體療法，有可能成為前列腺癌的一流資產，它是顯然是比神經內分泌腫瘤大得多的適應症。所以III期試驗正在進行中。我們將專注於快速入組該試驗，期待 2020 年的數據讀出和歸檔。

The other platform we are focused on is our cell therapy platform. And as Vas mentioned, Q4 has been a very important quarter for Kymriah. Sales for the year were $76 million, driven by both pancreatic, ALL and DLBCL, and we accelerated our sales growth in Q4 with $28 million. We have achieved reimbursement for one or both indications in 10 markets ex U.S. within 4 months following regulatory approval, and we continue discussions with payers in the other markets.

我們關注的另一個平台是我們的細胞治療平台。正如 Vas 所提到的，第四季度對 Kymriah 來說是一個非常重要的季度。在胰腺癌、ALL 和 DLBCL 的推動下，全年銷售額為 7600 萬美元，我們在第四季度以 2800 萬美元加速了銷售額增長。在監管部門批准後的 4 個月內，我們已經在美國以外的 10 個市場實現了一項或兩項適應症的報銷，我們將繼續與其他市場的付款人進行討論。

We continue to see very strong demand, driven by the very strong clinical profile that Kymriah has. Very durable responses with very consistent safety profile and the ability to use Kymriah in an outpatient setting is making us very confident of the increased demand for this therapy. As you see, based on this very strong clinical profile, we are now advancing into earlier lines of therapy, and we are also expanding into new hematological malignancies.

在 Kymriah 非常強大的臨床資料的推動下，我們繼續看到非常強勁的需求。非常持久的反應和非常一致的安全性以及在門診環境中使用 Kymriah 的能力使我們對這種療法的需求增加充滿信心。如您所見，基於這種非常強大的臨床特徵，我們現在正在推進早期治療，並且我們也在擴展到新的血液惡性腫瘤。

We also have made significant progress on our manufacturing process. We received approval to expand cell viability specifications in the U.S. We applied for this -- sorry, in Europe. We applied for the same in U.S., and we expect a similar approval there very soon. We also continue to build a global manufacturing footprint with a number of collaborations and regulatory approvals. You saw we have now 2 sites in the EU, but we also have ongoing collaborations in Asia. Altogether, we are working on a significant capacity expansion throughout 2019 and aim for an increase by fourfold in overall capacity. So we remain confident in this platform and very excited about the ongoing progress.

我們在製造過程中也取得了重大進展。我們在美國獲得了擴大細胞活力規格的批准。我們申請了這個 - 抱歉，在歐洲。我們在美國申請了同樣的申請，我們預計很快就會獲得類似的批准。我們還通過一系列合作和監管批准繼續建立全球製造足跡。你看到我們現在在歐盟有 2 個站點，但我們在亞洲也有持續的合作。總而言之，我們正在努力在整個 2019 年實現顯著的產能擴張，目標是將總產能增加四倍。因此，我們對這個平台充滿信心，並對不斷取得的進展感到非常興奮。

When we move to Slide 45 (sic) [Slide 44], there is 2 other compounds that I'm very excited about and where we are preparing for our launches. BYL719 is a potentially first treatment specifically for patients with the PIK3CA mutation. That's a mutation that is present in about 40% of HR+/HER2- advanced breast cancer patients, which is unfortunately associated with very poor prognosis. And BYL719 showed, in combination with fulvestrant, to double median PFS for this patient population compared to fulvestrant alone. So we are excited about this therapy. We have filed at the end of 2018. We are anticipating a launch in the second half of this year in the U.S.

當我們轉到幻燈片 45（原文如此）[幻燈片 44] 時，還有 2 種讓我非常興奮的化合物，我們正在為我們的發布做準備。BYL719 可能是第一個專門針對 PIK3CA 突變患者的治療方法。這種突變存在於大約 40% 的 HR+/HER2- 晚期乳腺癌患者中，不幸的是，這與非常差的預後有關。BYL719 與氟維司群聯合使用時，與單獨使用氟維司群相比，該患者群體的中位 PFS 翻了一番。所以我們對這種療法感到興奮。我們已經在2018年底提交了。我們預計將於今年下半年在美國推出。

The other therapy we are quite excited about is SEG101. That represents an important innovation in sickle cell disease by addressing vaso-occlusive crisis or VOCs. These are the hallmark of the disease and are associated with a decrease in quality of life and increased risk of organ damage and death. And unlike other treatments that are coming out, we have a hard endpoint, and our data shows significant reduction in the frequency of VOCs regardless of genotype or hydroxyurea use.

我們非常興奮的另一種療法是 SEG101。通過解決血管閉塞危機或 VOC，這代表了鐮狀細胞病的一項重要創新。這些是該疾病的標誌，與生活質量下降以及器官損傷和死亡風險增加有關。與即將出現的其他治療方法不同，我們有一個硬終點，我們的數據顯示無論基因型或羥基脲使用如何，揮發性有機化合物的頻率都會顯著降低。

So based on these results, we believe SEG101 will serve an important role for the 60% of the roughly 100,000 U.S. sickle cell disease patients who experience 2 or more VOCs per year. We have received FDA Breakthrough Therapy Designation in December, and we are planning for filing for the U.S. and EU in the first half of this year.

因此，基於這些結果，我們相信 SEG101 將為每年經歷 2 次或更多次 VOC 的大約 100,000 名美國鐮狀細胞病患者中的 60% 發揮重要作用。我們在 12 月獲得了 FDA 的突破性療法認定，我們計劃在今年上半年向美國和歐盟提交申請。

So as you can see, our Oncology business continues to exhibit strong growth. We have a number of unique and differentiated growth drivers, and I'm very excited to be leading this business.

正如您所看到的，我們的腫瘤業務繼續呈現強勁增長。我們擁有許多獨特且差異化的增長動力，我很高興能夠領導這項業務。

With that, over to you, Vas.

就這樣，交給你了，瓦斯。

Thank you, Susanne. So in closing, as you can see on Slide 46, we'll have a busy year in 2019. I won't go through everything on this slide, but as you -- the most important overall message is we're focusing -- as a leading medicines company, we're focusing on driving growth through a dynamic and exciting platform as well as building -- pipeline as well as building new platforms for growth. We're focused on productivity and margins in a way like we've ever been before. And we believe that combination will enable us to have a stronger growth profile and a more attractive business for years to come.

謝謝你，蘇珊娜。最後，正如您在幻燈片 46 中看到的那樣，我們將在 2019 年度過忙碌的一年。我不會詳細介紹這張幻燈片上的所有內容，但正如您 - 最重要的總體信息是我們正在關注 - 作為一家領先的醫藥公司，我們正在專注於通過一個充滿活力和令人興奮的平台以及建設——管道以及建立新的增長平台。我們以前所未有的方式關註生產力和利潤率。我們相信，合併將使我們在未來幾年擁有更強勁的增長前景和更具吸引力的業務。

So with that, I'll hand it over to Samir to lead the question-and-answer session.

因此，我將把它交給 Samir 來主持問答環節。

Okay. Operator, we're ready for the Q&A.

好的。接線員，我們準備好進行問答了。

(Operator Instructions) The first question this afternoon comes from the line of Graham Parry from Bank of America Merrill Lynch.

（操作員說明）今天下午的第一個問題來自美銀美林的格雷厄姆帕里。

So firstly, one for Harry on the guidance. On current business structure, the mid-single-digit core operating income, that's a few points below where consensus was. But when you stripped out Alcon, U.S. generics, it looked a little bit closer. So do you think essentially The Street has just been too optimistic on those businesses for this year? Or is there anything else you'd point to, for example, expectations around launches, for example? Secondly, on Zolgensma, more discussion in the trade press, and you just referred to yourself about being able to spread payments, an innovative payment structure. So could you perhaps dig in a little bit more detail on how far those negotiations have gone? Do you think those sort of payment structures will be in place in time for a midyear launch immediately post approval? Or do you see any reimbursement delay here post launch of the product? Could you also just clarify you comment there about breadth of label? And then, thirdly, on Gilenya, should we read the fact that you're guiding for no generics -- also your base-case scenario doesn't have generic in it this year. And on Slide 25, you seem to have pushed it towards 2020, '21 -- as implying confidence in lack of generic launch. And could you clarify if any of the generics have stated to the court an intent to launch at risk this year? And so should we expect preliminary injunction proceedings from yourselves this year?

所以首先，一個關於哈利的指導。根據當前的業務結構，中等個位數的核心營業收入比共識低幾個點。但是，當你剔除美國仿製藥公司 Alcon 時，它看起來更接近一點。那麼，您是否認為華爾街今年對這些企業過於樂觀了？或者您還有什麼要指出的，例如對發布的期望嗎？其次，關於 Zolgensma，在貿易媒體上進行了更多討論，您只是提到自己能夠分散支付，這是一種創新的支付結構。那麼，您能否更詳細地了解這些談判的進展情況？您認為這種支付結構是否會及時到位，以便在批准後立即推出年中？還是您在產品發布後看到任何報銷延遲？您能否也澄清一下您對標籤廣度的評論？然後，第三，在 Gilenya 上，我們是否應該讀到這樣一個事實，即你正在指導沒有泛型——而且你的基本案例場景今年也沒有泛型。在幻燈片 25 上，您似乎已將其推向 2020 年，即 21 年——這意味著對缺乏仿製藥發布的信心。您能否澄清是否有任何仿製藥已向法院聲明今年有風險推出的意圖？那麼我們應該期待今年你們自己的初步禁令程序嗎？

So first on guidance, Harry?

所以首先是指導，哈利？

Yes. Graham, so on the guidance overall, we see continued, as you see, for our new medicines company, strong growth profile, mid-single-digit growth despite a bit higher expected generic headwind but driven this mid-single digit, in Innovative Medicines and for new focused company, by our strong in-market brands and expected launches, but a bit of a headwind from Exjade and Afinitor expected generics, but I think it's very strong growth here with mid-single digits. And to the bottom line, clearly core operating income growing ahead of sales and driving margin expansion. Now when you go now to the current group structure, a bit at the lower level given that, for example, the U.S. solids business, [as when approached to investing], has a different growth or decline profile clearly. But of course, this guidance also has a certain range. So I would not see a weakness of Alcon, for example, where -- I'm sure David Endicott can comment, where we continue to expect the growth in the low to mid-single digit and also margin expansion. So from that standpoint, we see this as a clear guidance for a strong growth profile of the new focused company. And on the other hand also, I think maybe some of the analysts' work has not fully reflected the currency effect, which are there for 2019, which we are mentioning every month on our website. And this is a minus 3% on the bottom line if currencies stay where they are.

是的。格雷厄姆，所以關於總體指導，我們看到繼續，正如你所看到的，對於我們的新藥公司，強勁的增長前景，中等個位數的增長，儘管預期仿製藥逆風略高，但在創新藥物方面推動了這個中等個位數對於新的重點公司，通過我們強大的市場品牌和預期的推出，但 Exjade 和 Afinitor 預期的仿製藥有點逆風，但我認為這裡的增長非常強勁，中等個位數。最重要的是，核心營業收入的增長明顯領先於銷售額，並推動了利潤率的增長。現在，當你現在進入當前的集團結構時，考慮到例如美國固體業務（在接近投資時）具有明顯不同的增長或下降情況，因此處於較低水平。但當然，這個指導也是有一定範圍的。因此，我不會看到愛爾康的弱點，例如，我相信大衛恩迪科特可以發表評論，我們繼續預計中低個位數的增長以及利潤率的擴張。因此，從這個角度來看，我們認為這是對新重點公司強勁增長前景的明確指導。另一方面，我認為也許一些分析師的工作沒有完全反映 2019 年的貨幣效應，我們每個月都會在我們的網站上提到這一點。如果貨幣保持在原位，這就是負 3% 的底線。

And maybe I would just highlight there, I think strategically, for us, you can see that the new medicines company has just a stronger growth profile. We have a clear ability to grow in the mid-single digits, a clear ability to generate margin expansion and grow bottom line faster than top line, so we feel good. We're headed in the right direction and encourage investors to focus on that new company that we're creating.

也許我會在那裡強調，我認為從戰略上來說，對我們來說，你可以看到這家新藥公司的增長前景更為強勁。我們有明顯的中個位數增長能力，有明顯的利潤擴張能力和比收入增長更快的底線，所以我們感覺很好。我們正朝著正確的方向前進，並鼓勵投資者關注我們正在創建的新公司。

So moving to Zolgensma payment structure. Paul?

所以轉向 Zolgensma 支付結構。保羅？

So as you would imagine, we've been having a lot of detailed conversations with payers and the leading reimbursement. We -- I can tell you unequivocally we'll be ready with alternative payment models at launch. The installment approach has been well received in conversation, but it's not essential for everybody. But we will be with what we think is the most flexible way to come to market for the payers. And again, conversations have been very constructive with payers. Don't see an issue there. As for breadth of label, it's too early to say, to be honest. But I would add the word constructive again. I think we -- you expect the regulators, where they see such an opportunity for a foundational therapy, to try and be as constructive as possible. So we are on track with where we'd hope to be.

所以正如你想像的那樣，我們一直在與付款人和領先的報銷進行大量詳細的對話。我們——我可以明確地告訴你，我們將在發佈時準備好替代支付模式。分期付款的方式在談話中很受歡迎，但並不是每個人都必須這樣做。但我們將採用我們認為最靈活的方式為付款人進入市場。再一次，與付款人的對話非常有建設性。看不到那裡的問題。至於標籤的廣度，老實說，現在說還為時過早。但我要再次加上建設性這個詞。我認為我們 - 你希望監管機構在他們看到基礎療法的機會時嘗試盡可能具有建設性。所以我們正朝著我們希望的方向前進。

Great. So on Gilenya, I'll have Shannon, our Legal Counsel, take that.

偉大的。所以關於 Gilenya，我會讓我們的法律顧問 Shannon 接手。

So Graham, as you know, the compound patent in Gilenya expires in August 2019, so no generic launch prior to that. In July of last year, the Patent and Trademark Office upheld the validity of our 2027 dosage regimen patent, which means generics can't launch against that patent unless they do so at risk. In parallel to the patent office decision, we did file a lawsuit against 23 generics companies, seeking to enforce that 2027 dosage regimen patent. Eleven of those companies have refused to indicate whether they will launch at risk or not, and so we will engage in preliminary injunction proceeding. Just this week, the court has scheduled a June 21 hearing on our preliminary injunction motion, which we hope will give clarity to the status of that preliminary injunction as to the 2027 patent prior to August 2019. The bottom line in all of this is that you can only see generics launch at risk either if they win the preliminary injunction hearing in June or if the patent is declared invalid either through the IPR process, where we expect the appeal to be decided in Q4 of this year or even the first half of next year; or if the patent is invalidated by the district court, where the hearing is currently set for March of 2020. And it's 3 to 6 months, Graham, after that for us to see a decision. And then of course if the decision doesn't go our way, we will appeal. And so we feel good about the guidance we've given and look forward to the arguments in the court.

所以 Graham，正如你所知，Gilenya 的化合物專利將於 2019 年 8 月到期，因此在此之前沒有仿製藥上市。去年 7 月，專利商標局維持了我們 2027 劑量方案專利的有效性，這意味著除非冒著風險，否則仿製藥不能針對該專利上市。在專利局做出決定的同時，我們確實對 23 家仿製藥公司提起訴訟，尋求執行 2027 年劑量方案專利。其中 11 家公司拒絕表明他們是否會冒著風險推出產品，因此我們將進行初步禁令程序。就在本週，法院已安排在 6 月 21 日就我們的初步禁令動議舉行聽證會，我們希望這將在 2019 年 8 月之前澄清關於 2027 年專利的初步禁令的狀態。所有這一切的底線是，如果仿製藥在 6 月贏得初步禁令聽證會，或者專利通過 IPR 程序被宣布無效，那麼您只能看到仿製藥上市面臨風險，我們預計上訴將在第四季度做出決定今年甚至明年上半年；或者如果專利被地方法院宣告無效，聽證會目前定於 2020 年 3 月舉行。格雷厄姆，我們需要 3 到 6 個月才能做出決定。當然，如果決定不符合我們的意願，我們將提出上訴。因此，我們對我們給出的指導感到滿意，並期待在法庭上進行辯論。

Great.

偉大的。

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

下一個問題來自花旗銀行的 Andrew Baum。

Three questions, please. Firstly, Vas, you were quoted at Davos as talking about the danger of reforming U.S. reimbursement system the government plans in an overly hasty (inaudible) consequences. Were you thinking of any particular part of the proposed reform in mind? On the same topic, could you comment on how you're thinking about proposed net pricing shift by removal of the safe harbors? Second, on Sandoz, should we imagine that, once you've divested U.S. solid, the residual of the Sandoz business, albeit pruned and optimized, is going to be a long-term part of the (inaudible) structure? Or is this being improved with a few potential divestments down the track, both core and noncore? And then finally, could you just say something regarding your large but still as yet undisclosed early-stage immuno-oncology assets? There should be a number of combinations with your internal PD-1 with some promising agent. When do we expect the data? Should we expect (inaudible) some time at year-end?

請教三個問題。首先，瓦斯，你在達沃斯被引述為談論改革美國報銷制度的危險政府計劃在過於倉促（聽不清）的後果。您是否想到了擬議改革的任何特定部分？在同一主題上，您能否評論一下您是如何考慮通過移除安全港來改變淨定價的？其次，關於 Sandoz，我們是否應該想像，一旦您剝離了 U.S. solid，Sandoz 業務的剩餘部分（儘管經過修剪和優化）將成為（聽不清）結構的長期組成部分？還是通過一些潛在的核心和非核心資產撤資來改善這種情況？最後，您能否談談您龐大但仍未公開的早期免疫腫瘤學資產？您的內部 PD-1 與一些有前途的藥物應該有多種組合。我們什麼時候需要數據？我們應該期待（聽不清）年底的某個時間嗎？

Andrew, so first, with respect to U.S. reimbursement, I think my comments were really regarding some of the comments that are being made currently in Washington to take I think what could be I think longer-term destructive actions, things like reimportation, reference pricing, et cetera, none of which I expect to have happen. Nonetheless, I would want to be sure that we don't take an action without thinking -- the government doesn't take an action without considering the consequences for the entire system. We've been proponents for looking at how do we ensure rebates and other payments within the supply chain; enable patients to have more affordability at the pharmacy counter; continuing to reform programs that may have distortions in them, including Part B, 340B, et cetera; ensuring that we have a playing field that enables competition after appropriate amount of patent protection, and we need strong IP of course to enable innovation, but then after that, to limit gaming or other elements that prevent generic entry and prevent a robust generic environment, including biosimilars, where I think we continue to see the U.S. lag Europe in terms of the overall uptake of biosimilars. So those are some of the elements. I'm sure there are others. But I think we need a comprehensive approach. Now with respect to the discussions on the safe harbor and removing the safe harbor on rebates, it's difficult still to judge exactly how that will impact our pricing approach until we see the details of what exactly is being proposed and then how the system will react to those changes. I think we've seen assessments that indicate a range of potential outcomes depending on how this is done. So I think until we see more details, it will be difficult to comment. So we'll just keep up with it as the quarters go on.

安德魯，首先，關於美國的報銷，我認為我的評論實際上是關於華盛頓目前正在發表的一些評論，我認為我認為可能是長期的破壞性行動，比如重新進口、參考定價，等等，我希望這些都不會發生。儘管如此，我想確保我們不會在沒有考慮的情況下採取行動——政府不會在沒有考慮對整個系統的後果的情況下採取行動。我們一直支持研究如何確保供應鏈中的回扣和其他付款；使患者在藥房櫃檯有更多的負擔能力；繼續改革可能存在扭曲的計劃，包括 B 部分、340B 等；確保我們有一個競爭環境，在適當的專利保護後能夠進行競爭，我們當然需要強大的知識產權來實現創新，但在那之後，要限制遊戲或其他阻止仿製藥進入並防止強大的仿製藥環境的因素，包括生物仿製藥，我認為我們繼續看到美國在生物仿製藥的整體採用方面落後於歐洲。所以這些是一些要素。我確定還有其他人。但我認為我們需要一個全面的方法。現在關於安全港和取消回扣安全港的討論，仍然很難準確判斷這將如何影響我們的定價方法，直到我們看到具體提議的細節以及系統將如何反應那些變化。我認為我們已經看到評估表明一系列潛在結果取決於如何完成。所以我認為，在我們看到更多細節之前，很難發表評論。所以我們會隨著季度的進行而跟上它。

Now with respect to Sandoz, there's no change in our position. We consider Sandoz an integral part of Novartis. We're focused on transforming the business, making it an autonomous entity over the next 18 months that is able to compete as an independent unit within Novartis. That's where our complete focus is at the moment. That in itself is a major effort, a significant transformation we make in Sandoz, both in terms of cost structure, in terms of geographic focus, in terms of product portfolio, as well as let's call it the de-integration of Sandoz from the rest -- elements of Novartis where it's been integrated will take us 18 months. And I think after we complete all of that, then I think we can have further conversations about where we want to head from there.

現在關於 Sandoz，我們的立場沒有改變。我們認為山德士是諾華不可分割的一部分。我們專注於業務轉型，使其在未來 18 個月內成為一個自治實體，能夠作為諾華內部的一個獨立部門參與競爭。這就是我們目前完全關注的地方。這本身就是一項重大努力，我們在 Sandoz 中進行的一次重大轉變，無論是在成本結構、地理重點、產品組合方面，還是我們稱之為 Sandoz 與其他公司的去整合——整合諾華的元素將花費我們 18 個月的時間。而且我認為在我們完成所有這些之後，我認為我們可以就我們想要從那裡走向何方進行進一步的對話。

And then lastly, in terms of our early-stage I/O portfolio, we continue to explore, I think, the full range of 20-plus I/O assets that we've had. We have a few readouts that we think look exciting, and we're currently working to advance those. And I think as soon as we get to the point of starting the next studies, we'll disclose those publicly. I would say, in general, as has been the case I think for others in the industry, many of these second-generation I/O assets have not proven themselves to add significantly over PD-1. So we've chosen to have a very high bar. You've heard me say that before. But I would say there's -- there are a few that we are looking into in much more depth, and we hope to give you an update as the year progresses. I would expect that -- those updates to happen either in Q1 or Q2.

最後，就我們的早期 I/O 產品組合而言，我認為我們將繼續探索我們擁有的 20 多種 I/O 資產的全部範圍。我們有一些我們認為看起來令人興奮的讀數，我們目前正在努力推進這些。我認為，一旦我們開始下一項研究，我們就會公開披露這些內容。我想說的是，一般來說，正如我認為業內其他人的情況一樣，這些第二代 I/O 資產中的許多都沒有證明自己比 PD-1 有顯著增加。所以我們選擇了一個非常高的標準。你以前聽我說過。但我要說的是 - 我們正在更深入地研究一些問題，我們希望隨著時間的推移向您提供更新。我希望 - 這些更新將在第一季度或第二季度發生。

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

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

A couple of questions. You've done a good and comprehensive job articulating various drivers of revenue growth for Novartis through in-line brands and new pipeline launches. But for the sake of fair balance, I'm hoping you can also talk about what the drags on top line growth are, not just in '19 but maybe in '20 as well, so over a couple-year period. And I'm not talking about systemic headwinds like U.S. price reform, but really company-specific headwinds, whether it's competitive challenges to in-line brands or upcoming generic launches and that sort of thing.

幾個問題。您通過在線品牌和新產品線的推出，很好地闡述了諾華收入增長的各種驅動因素。但為了公平起見，我希望你也能談談對收入增長的拖累，不僅僅是在 19 年，也可能在 20 年，所以在幾年的時間裡。而且我不是在談論像美國價格改革這樣的系統性逆風，而是真正針對公司的逆風，無論是對在線品牌的競爭挑戰還是即將推出的仿製藥等等。

Second question is on emerging markets and your performance. You have one of the larger global footprints among peer companies. If I look at your performance, it's good, it's not great. I'm wondering what could change this versus just how the chips fall in terms of the portfolio of products you sell there. And can you talk about the prospects in China as well and what you see happening in terms of market reform and whether there are pressures that could push growth lower in China specifically?

第二個問題是關於新興市場和你們的表現。在同行公司中，您擁有更大的全球足蹟之一。如果我看你的表現，那很好，不是很好。我想知道什麼可以改變這一點，而不是芯片在您在那裡銷售的產品組合方面的下降情況。您能否也談談中國的前景以及您在市場改革方面看到的情況，以及是否存在可能導致中國經濟增長放緩的壓力？

Great. Thanks, Tim. I think on revenue growth, I'll name I think a few key drivers in my mind, and then I'll look around the room to see if any colleagues who want to pick up anything else. As we said, as Harry said, the generic entries in Exjade and Afinitor -- Exjade later this year, Afinitor in early 2020, I think is something we'll have to overcome. We feel confident we can overcome those 2 generic entries. But I think those will be 2 key ones we'll have to say on top of. In addition, of course, as we've discussed the Gilenya situation, let's say, we feel good now about 2019, and we'll have to see how the events evolve over the coming year to see -- year and year and a half to see when Gilenya might have any generic entrants in the future. Votrient, where we did take an impairment, is broadly related to the slowdown we saw in the back half of 2018, primarily driven by the entrants of PD-1 combinations in renal cell carcinoma. That's one where overall our other GSK -- assets acquired from GSK outperform, like MEKINIST and Tafinlar as well as PROMACTA and Revolade. But with Votrient, we do expect there to be more headwinds in the coming period. And then the other, I think, wildcard out there, which has been out there for us for 15 years, is Sandostatin LAR and any potential generic entrants for Sandostatin LAR. Those are some of the big, top-line headwinds we see. But I think, again, relative to the strength of our in-line brands and the upcoming launches, we feel confident we can grow consistently over the coming period. Harry, anything else you would add?

偉大的。謝謝，蒂姆。我認為在收入增長方面，我會說出我認為的幾個關鍵驅動因素，然後我會環顧房間，看看是否有同事想要拿起其他東西。正如我們所說，正如 Harry 所說，Exjade 和 Afinitor 中的通用條目——今年晚些時候的 Exjade，2020 年初的 Afinitor，我認為這是我們必須克服的問題。我們相信我們可以克服這 2 個通用條目。但我認為這些將是我們不得不說的 2 個關鍵問題。此外，當然，正如我們討論過 Gilenya 的情況，假設我們現在對 2019 年感覺良好，我們將不得不看看事件在來年的發展情況 - 一年和一年半看看 Gilenya 將來什麼時候可能會有任何仿製藥進入者。我們確實受到損害的 Votrient 與我們在 2018 年下半年看到的放緩廣泛相關，這主要是由腎細胞癌中 PD-1 組合的進入者推動的。這是我們其他葛蘭素史克的總體表現——從葛蘭素史克收購的資產，如 MEKINIST 和 Tafinlar 以及 PROMACTA 和 Revolade。但對於 Votrient，我們確實預計在未來一段時間內會有更多的逆風。然後另一個，我認為，已經存在了 15 年的通配符是 Sandostatin LAR 和 Sandostatin LAR 的任何潛在仿製藥。這些是我們看到的一些重大的頂線逆風。但我再次認為，相對於我們在線品牌的實力和即將推出的產品，我們有信心在未來一段時間內持續增長。哈利，你還有什麼要補充的嗎？

No, those are the main ones. Thank you.

不，那些是主要的。謝謝。

So then moving to emerging growth markets, maybe, Paul, do you want to say a word about where we are and then where we are in China, specifically?

那麼接下來轉向新興增長市場，保羅，你想談談我們在中國的位置以及我們在中國的位置嗎？

So I think, Tim, I can see where you get that perception from. Some of it is portfolio-driven. But if I look at the last couple of years of our increasing investment in China, the sort of, I think industry-leading NRDL listing last year, as we transition our portfolio from some of the older medicines and conclude some divestments, we end up with real growth drivers positioned in China with the investments deployed. So we look forward to gathering some momentum and revisiting China as a real growth opportunity with what we have in market. So watch this space is probably what I would say about China.

所以我想，蒂姆，我可以看出你是從哪裡得到這種看法的。其中一些是投資組合驅動的。但如果我回顧過去幾年我們在中國不斷增加的投資，我認為是去年行業領先的 NRDL 上市，因為我們將我們的投資組合從一些老藥中轉移並完成一些撤資，我們最終真正的增長動力位於中國，並部署了投資。因此，我們期待著聚集一些勢頭，並重新訪問中國，將其視為我們在市場上的真正增長機會。所以看這個空間可能就是我要說的中國。

Thank you, Paul. Well, any other comments on emerging growth markets? Paul -- I mean Tim, I'll just make a general comment. I mean, we continue to see strong growth in our established medicines portfolio in emerging growth markets. Actually, we do very well with that portfolio. I think one of the things we're aiming to do through emerging growth brands as well as other strategies to get access to our more innovative medicines more quickly in a broad set of geographies. We don't necessarily see that as a near-term growth driver, but hopefully in the medium term, we can start to build the innovation -- interest in these markets to hopefully drive growth in the future.

謝謝你，保羅。那麼，還有關於新興增長市場的其他評論嗎？保羅——我是說蒂姆，我只是做一個一般性的評論。我的意思是，我們繼續看到我們在新興增長市場的成熟藥物組合的強勁增長。實際上，我們在該投資組合方面做得很好。我認為我們的目標之一是通過新興增長品牌以及其他戰略來在廣泛的地區更快地獲得我們更具創新性的藥物。我們不一定將其視為近期增長動力，但希望在中期，我們可以開始建立創新——對這些市場的興趣，以期推動未來的增長。

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

下一個問題來自瑞士信貸的 Matthew Weston。

Two questions, if I can. The first on AVXS-101 and the data in Type 2 SMA. You've highlighted we'll see the data at AAN in May, but filing not scheduled until 2020. So if you can explain why or what additional we're going to see between AAN and what's required for filing, that would be extremely helpful. And then secondly, just regarding your comments on capital deployment, Vasant, and particularly the comments around bolt-on M&A. Clearly, the dividend has grown for its 22nd year, but only up 2%, which is meaningfully different from where earnings grew and also the earnings guidance outlook. With your comment that you'd like to see a consistent level of bolt-ons, and then you flagged $15 billion, are you suggesting that we should be expecting a relatively meaningful number each year? Or just that bolt-ons remain a key element of the strategy?

兩個問題，如果可以的話。第一個關於 AVXS-101 和 2 型 SMA 中的數據。您已經強調我們將在 5 月份在 AAN 上看到數據，但要到 2020 年才能提交文件。因此，如果您能解釋為什麼或我們將在 AAN 和備案要求之間看到什麼額外內容，那將非常有幫助。其次，關於你對資本部署的評論，Vasant，特別是關於補強併購的評論。顯然，股息已連續第 22 年增長，但僅增長 2%，這與收益增長和收益指導前景大不相同。根據您的評論，您希望看到一致的補強水平，然後您標記了 150 億美元，您是否建議我們每年應該期待一個相對有意義的數字？或者僅僅是補強措施仍然是該戰略的關鍵要素？

Great. So first on AAN. John, do you want to take that?

偉大的。所以首先在 AAN 上。約翰，你要拿那個嗎？

Thanks, Matthew. Regarding AVXS-101, as you know, STRONG is our Phase I study using our intrathecal formulations for Type 2 patients. That study is ongoing. We have 3 different dosages being studied, and the mid-dose is fully recruited. And that study is advancing well. We also know from history that the Type 1 results are predictive of Type 2 and Type 3 patients, so we're looking forward to sharing that information in May with AAN. And based on the results that we get, we will use that information for the filing. So that timeline I think will be really dependent on what the data shows us, and you'll be seeing more of that in May.

謝謝，馬修。關於 AVXS-101，如您所知，STRONG 是我們的 I 期研究，使用我們的鞘內製劑治療 2 型患者。該研究正在進行中。我們正在研究 3 種不同的劑量，中劑量已完全招募。這項研究進展順利。我們還從歷史中了解到，1 型結果可以預測 2 型和 3 型患者，因此我們期待在 5 月份與 AAN 分享該信息。根據我們得到的結果，我們將使用該信息進行備案。因此，我認為該時間表將真正取決於數據向我們展示的內容，您將在 5 月份看到更多這樣的數據。

And so, Harry -- I think Harry wanted to make a comment on the dividend before I take on bolt-on M&A.

因此，Harry——我認為 Harry 想在我進行補強併購之前對股息發表評論。

Yes, just -- Matthew, I just want to make one comment on the dividend. First of all -- actually two. First of all, we have to see this over multiple years. So we also increased the dividend in years where we didn't have earnings growth or free cash flow growth with major patent expirations, as you know. And the other -- and we are quite well placed, I would say, from 1% payout of free cash flow and the dividend yield in the peer group. And second of all, one has to remember, assuming the high likelihood that the Alcon spin gets approved at the AGM, we will not rebase our dividends. So the remaining Novartis dividends is expected to grow from the current base of CHF 2.85. So that, I think, is another important aspect of our dividend policy.

是的，只是 - 馬修，我只想對股息發表評論。首先——實際上是兩個。首先，我們必須在多年後看到這一點。因此，如您所知，我們還增加了在主要專利到期時我們沒有盈利增長或自由現金流增長的年份的股息。另一個 - 我想說，我們處於相當有利的位置，從 1% 的自由現金流支出和同行組的股息收益率。其次，必須記住，假設愛爾康分拆在年度股東大會上獲得批准的可能性很高，我們將不會調整我們的股息。因此，剩餘的諾華股息預計將從目前的 2.85 瑞士法郎基數增長。因此，我認為這是我們股息政策的另一個重要方面。

Great, Harry. And then in terms of bolt-on M&A, the way I think about it, the way we think about it is we want to be consistently trying to do M&A in the range of up to 5% of our market cap, right. Which would really be in that up-to $10 billion range. But I think what drives us is having good assets and assets where we can generate a strong return for the company and build in our core therapeutic areas and in these new technology areas, advanced therapy platforms, where we want to lead. So we want to try to hit a target, so to say, on M&A, but I think we have our minds open to the fact that, in order to build a more and more valuable company over time, bolt-on M&A has to be part of that strategy along with our in-line portfolio. And that's the way we're going to approach it.

太好了，哈利。然後就補強併購而言，我的思考方式，我們的思考方式是，我們希望始終如一地嘗試在我們市值的 5% 範圍內進行併購，對吧。這真的會在高達 100 億美元的範圍內。但我認為推動我們的是擁有良好的資產和資產，我們可以在這些資產和資產中為公司帶來豐厚的回報，並在我們的核心治療領域以及我們希望引領的這些新技術領域、先進的治療平台上進行建設。所以我們想嘗試在併購方面達到一個目標，但我認為我們對這樣一個事實持開放態度，為了隨著時間的推移建立一家越來越有價值的公司，補強併購必須是該戰略的一部分以及我們的在線產品組合。這就是我們處理它的方式。

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

下一個問題來自摩根大通的 Richard Vosser。

First question just on Alcon. The margins were called out a little bit lower than expected due to higher promotional spend. So could you give us some extra color on where the spend was targeted, whether we should extrapolate that going forward or whether there's any element of a pull-through from 2019 into '18? Second question just on COSENTYX. I think you've highlighted, but please, could you just repeat again? That COSENTYX will grow quarter-on-quarter over fourth quarter -- in the first quarter of '19. But secondly, on COSENTYX, could you give us an idea of how you see future competition coming in, I suppose, from AbbVie on 2020 on the COSENTYX product? And also, maybe give us an idea of how the growth is looking in psoriatic arthritis and ank spon, just whether you are seeing any impact from the JAK inhibitors there. And then final question, I suppose, on Sandoz. Clearly, I think there are expectations of biosimilar growth in the market and from you. So when we exclude the oral solids business decline, what other things are leading to sales being broadly in line year-on-year? Is there any -- are there any other pressures that we should think about there?

關於愛爾康的第一個問題。由於促銷支出增加，利潤率略低於預期。那麼，您能否給我們一些關於支出目標的額外顏色，我們是否應該推斷未來的支出，或者是否有從 2019 年到 18 年的任何因素？關於 COSENTYX 的第二個問題。我想你已經強調了，但是請你再重複一遍好嗎？COSENTYX 將在 19 年第一季度的第四季度環比增長。但其次，關於 COSENTYX，你能否告訴我們你如何看待未來的競爭，我想，2020 年來自 AbbVie 的 COSENTYX 產品？而且，也許讓我們了解銀屑病關節炎和踝關節的生長情況，看看你是否看到 JAK 抑製劑的影響。最後一個問題，我想，關於 Sandoz。顯然，我認為市場和您對生物仿製藥的增長抱有期望。那麼，當我們排除口服固體業務下滑時，還有哪些其他因素導致銷售額與去年同期大致持平？有沒有——我們應該考慮其他壓力嗎？

Thanks, Richard. Let's start with David on the margins.

謝謝，理查德。讓我們從邊緣的大衛開始。

Right. Thanks, Richard, for the question. First of all, let me say I'm pleased with another solid quarter, sales growth at 4%. We had a strong turnout in surgical at 6%, continued growth in emerging market. That gives us a really good run from where we started at 5% for the full year. So we're feeling good about the revenue side of it. But on the fourth quarter specifically, we continued our planned investments behind some of our core long-term drivers, PanOptix, DT1 Multifocal, SUSTAIN complete. And we continued spending on operational improvements such as the SAP deployment and some of the proposed spin-off areas. So the fourth quarter margin came in where we had planned it to be. And as Harry indicated, we were pleased with the 80 basis point improvement over what was our trough year of 2017. So going forward, we haven't given specific margin guidance for '19 other than to say we intend for it to be accretive to 2018. And there's really no change to that position. But once we are spun off, we intend to be more granular about the '19 guidance. So we'll go forward from there.

正確的。謝謝理查德提出這個問題。首先，讓我說我對又一個穩健的季度感到滿意，銷售增長率為 4%。我們在外科手術方面的投票率很高，達到 6%，新興市場持續增長。這讓我們從全年 5% 的起點開始有了非常好的表現。所以我們對它的收入方面感覺很好。但特別是在第四季度，我們繼續在我們的一些核心長期驅動因素背後進行計劃投資，PanOptix、DT1 Multifocal、SUSTAIN complete。我們繼續在運營改進方面投入資金，例如 SAP 部署和一些擬議的衍生領域。因此，第四季度的利潤率達到了我們計劃的水平。正如 Harry 所指出的，我們很高興與 2017 年的低谷年度相比提高了 80 個基點。因此，展望未來，我們沒有給出 19 年的具體利潤率指導，只是說我們打算將其增加到 2018 年。而且這個位置真的沒有改變。但是一旦我們被分拆出來，我們打算更細化 19 年的指導方針。所以我們將從那裡繼續前進。

Thanks, David. Moving to Paul.

謝謝，大衛。搬到保羅。

Thanks, Richard. Important to clarify this. I want to be as clear as possible. So what I said was year-on-year growth, we're confident in. I said that Q1 '19 over Q1 '18, again, you should expect significant growth. Now specifically, Q1 '19 over Q4 '18, I think that's what you're asking. We will be broadly in line. There's some benefit reverification, some co-pay reset, some finessing and all those things, but broadly in line. We expect to grow our volume and be close to, if not on what we did in Q4. Is that -- I think that's clear enough. On new entrants, risankizumab is probably the last major entrant to the market and which is why it's so pleasing for us to be at least currently leader of the new entrants. Sets us up for the long term. Whilst not particularly concerned about the clinical profile of risankizumab, I think another IL-23 -- will be another IL-23, I think, AbbVie must be taken somewhat seriously because of the heritage and leverage in the market. So we are hypervigilant about what that could mean, but I can assure you we're well prepared. As for the JAK inhibitors, there's been a little bit of a discussion over the last few days based on a survey, which I think will also contain the disclaimer about what it meant in NWRx. I think the question is PsA and AS. NWRx is not really linked to NBRx. We haven't seen any connection. So I just want to be really clear again. The JAKs have around A 2% new patient share in the U.S. And that is PsA and AS. The JAK safety profile -- the current JAK has maybe a black box warning -- is not in the same -- not -- can't be compared with the newer classes of monoclonal antibodies. So we expect of course promotion as more enter the market, but we think IL-17 and in particular COSENTYX will be the standard of care in AS and PsA, and we've seen nothing to make us think differently at this point.

謝謝，理查德。澄清這一點很重要。我想盡可能清楚。所以我說的是同比增長，我們有信心。我說過，19 年第一季度超過 18 年第一季度，你應該期待顯著增長。現在具體來說，19 年第一季度超過 18 年第四季度，我想這就是你要問的。我們將大體一致。有一些福利重新驗證，一些共同支付重置，一些技巧和所有這些東西，但大致一致。我們希望增加我們的數量並接近，如果不是我們在第四季度所做的。是嗎——我認為這已經足夠清楚了。在新進入者方面，risankizumab 可能是市場上最後一個主要進入者，這就是為什麼我們很高興至少目前成為新進入者的領導者。為我們做好長期準備。雖然不是特別關心 risankizumab 的臨床特徵，但我認為另一種 IL-23——將是另一種 IL-23，我認為，由於市場的傳統和影響力，必須認真對待 AbbVie。所以我們對這可能意味著什麼保持高度警惕，但我可以向你保證我們已經做好了充分的準備。至於 JAK 抑製劑，過去幾天根據一項調查進行了一些討論，我認為這也將包含關於它在 NWRx 中的含義的免責聲明。我認為問題是 PsA 和 AS。NWRx 並沒有真正鏈接到 NBRx。我們沒有看到任何联系。所以我只想再次說清楚。JAK 在美國約有 2% 的新患者份額，即 PsA 和 AS。JAK 安全概況——當前的 JAK 可能有一個黑框警告——不一樣——不——不能與更新的單克隆抗體類別進行比較。因此，我們當然希望隨著更多藥物進入市場而得到推廣，但我們認為 IL-17，尤其是 COSENTYX 將成為 AS 和 PsA 的治療標準，目前我們還沒有看到任何讓我們有不同想法的東西。

Thank you, Paul. And on biosimilars growth dynamics and other growth dynamics in Sandoz, Richard?

謝謝你，保羅。關於山德士生物仿製藥的增長動力和其他增長動力，理查德？

Richard, so yes, to answer your question firstly on the growth dynamics. The aim of the transformation that Vas has outlined in his presentation today is aimed at driving growth on the top and the bottom line. Now I think the growth will be tempered somewhat by the transformation in that we'll be rationalizing our SKUs and stepping out of some geographies, which we don't see as long-term growth drivers of the top and bottom line. So you sort of have to manage that. But the underlying growth is there, and that's primarily driven by the biosimilars. As you've highlighted, we finished quarter 4 with a 29% growth, the full year is 24% growth. We launched adalimumab, pegfilgrastim and infliximab in quarter 4. So I think we have really good momentum there, and we see that continuing. But as we work through that transformation, we are just going to have to deal with that as they -- as those SKUs, as those geographical exits start to have impact. But underlying growth, we're confident and there will be margin expansion as we move forward over the years as we get -- exit that transformation.

理查德，是的，首先回答你關於增長動力的問題。Vas 在今天的演講中概述的轉型目標旨在推動收入和利潤的增長。現在我認為增長會因轉型而有所緩和，因為我們將合理化我們的 SKU 並走出一些地區，我們認為這些地區不是收入和利潤的長期增長動力。所以你有點必須管理它。但潛在的增長是存在的，這主要是由生物仿製藥推動的。正如您強調的那樣，我們在第四季度結束時增長了 29%，全年增長了 24%。我們在第 4 季度推出了阿達木單抗、培非格司亭和英夫利昔單抗。所以我認為我們在那裡的勢頭非常好，而且我們看到這種勢頭還在繼續。但是，當我們完成這種轉變時，我們將不得不處理它們——因為那些 SKU，因為那些地理出口開始產生影響。但潛在的增長，我們有信心，隨著我們在過去幾年中的前進，利潤率將會擴大——退出轉型。

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

下一個問題來自高盛的 Keyur Parekh。

I've got 3 questions, please. The first one on your comments on Sandoz, Vas. I think on your podcast earlier this year, you said about 80% of all medicines that Novartis sell is via Sandoz. As you think about rationalizing or prioritizing certain geographies for Sandoz, can you give us a scope for how much complexity you can take out of the broader Novartis complex over the next 12, 18 months and what that means relative to your ability to refocus on the innovative core? That's question number one. Question number two is, again, kind of capital allocation, whether you've got a reasonably large asset sitting on your balance sheet in sense of the Roche stake. Any updates there on your thoughts? And especially, as you look at financing some of the bolt-on transactions you're talking about, how should we think about your willingness to use that stake? And thirdly, in sense of longer-term margin trajectory, obviously, we'll see some margin upgrade -- kind of broader margin uplift next year. But as you move towards the mid-30s guidance that you provided to, should we think of it as being linear? Or should we think of it as taking a rest in 2020 as you face some of the drags and then reenergizing after that?

我有3個問題，請。第一個關於你對 Sandoz，Vas 的評論。我想在你今年早些時候的播客中，你說諾華公司銷售的所有藥物中約有 80% 是通過 Sandoz 銷售的。當您考慮為 Sandoz 合理化或優先考慮某些地區時，您能否給我們一個範圍，說明您在接下來的 12 個月、18 個月內可以從更廣泛的諾華綜合體中消除多少複雜性，以及這對您重新專注於創新核心？這是第一個問題。第二個問題再次是某種資本配置，你的資產負債表上是否有相當大的資產，就羅氏股份而言。您的想法有任何更新嗎？特別是，當你考慮為你正在談論的一些補強交易提供資金時，我們應該如何考慮你使用這些股份的意願？第三，就長期利潤率軌跡而言，顯然，我們會看到一些利潤率提升——明年會有更廣泛的利潤率提升。但是，當您朝著您提供的 30 年代中期指導前進時，我們是否應該將其視為線性的？或者我們應該把它看作是在 2020 年休息一下，因為你要面對一些阻力，然後重新振作起來？

Thanks for the question. Maybe I'll take the manufacturing question in the broader context. We have multiple things going on right now in our manufacturing footprint. We have significant amount of idles overall in the footprint across all of the different business lines. And so that's why we've taken the actions we've taken over the course of 2018 with the 16 actions I mentioned. And we'll have additional actions planned over the course of this year to really get the idles down. Then the second is with respect to the complexity within our manufacturing footprint. And that's more what Richard was referring to. There, we know that because of the scale and scope of Sandoz, we have -- how many SKUs, Richard?

謝謝你的問題。也許我會在更廣泛的背景下處理製造問題。在我們的製造足跡中，我們現在正在進行多項工作。我們在所有不同業務線的足跡中都有大量閒置。這就是為什麼我們在 2018 年採取了我提到的 16 項行動。我們將在今年計劃採取更多行動，以真正減少閒置。其次是關於我們製造足跡內的複雜性。而這正是理查德所指的。在那裡，我們知道由於 Sandoz 的規模和範圍，我們有多少 SKU，Richard？

25,000.

25,000。

So we have 25,000 SKUs. And our goal over the course of this year geographic focusing is to exit some of the SKUs that we either think are not going to be as valuable and hopefully also reduce the complexity of the overall operation. And so combined, we think both the Sandoz sharpening of focus as well as our overall broader effort to rationalize our footprint will get to us -- get us to a better place in terms of manufacturing costs, gross margins, inventory level, cash conversion cycle, all of the downstream elements were having a more streamlined operation. Now with respect to the Roche stake, there's no change on our status on the Roche stake. As soon as there is a change, we'll of course update the market. We have more than adequate free cash flow as well as strength of the balance sheet to fund our bolt-on acquisition levels that we are currently at for the future. And then lastly, in terms of the long-term margins, we expect our margin accretion to happen in a consistent way over the coming years. We believe we can do that because it's a combination not only of the top line driving this margin expansion, but also the consistent approach we're taking to taking costs out of the various units. So our expectation is not precisely linear, we don't give that kind of guidance, but more a linear, consistent approach to margin expansion over time.

所以我們有 25,000 個 SKU。在今年的地理重點過程中，我們的目標是退出一些我們認為不會那麼有價值的 SKU，並希望還能降低整體運營的複雜性。綜上所述，我們認為 Sandoz 的關注重點以及我們為合理化我們的足跡所做的整體更廣泛的努力都會幫助我們——讓我們在製造成本、毛利率、庫存水平、現金轉換週期方面處於更好的位置，所有下游元素的操作都更加精簡。現在關於羅氏股份，我們在羅氏股份中的地位沒有變化。一旦有變化，我們當然會更新市場。我們有足夠的自由現金流和強大的資產負債表來為我們目前為未來的補強收購水平提供資金。最後，就長期利潤率而言，我們預計我們的利潤率增長將在未來幾年以一致的方式發生。我們相信我們可以做到這一點，因為這不僅是推動利潤率增長的頂線的結合，也是我們為降低各個部門的成本而採取的一貫方法。所以我們的期望不是精確的線性，我們沒有給出那種指導，而是隨著時間的推移，一種線性的、一致的利潤率擴張方法。

Next question comes from the line of Florent Cespedes from Societe Generale.

下一個問題來自法國興業銀行的 Florent Cespedes 系列。

I have 3 product-related questions. First, on cancer for Susanne. First, on BYL. Could you share with us how you will position the product? It's now part of the drugs with a blockbuster potential. Could it be positioned as a second line after CDK just before Afinitor? Some color on this front would be very helpful. Second question still on cancer drugs. On Kisqali, I would think you believe we should think about Kisqali sales trajectory. What should boost the sales and prescriptions? Is it the geographical expansion, market access or any new indications? And last but not least, quick questions on RTH. The filing is a little bit delayed from end of last year to February this year. Do we have to understand that there is anything behind that? Is there any requirement for additional data or whatever? Could you clarify on this point?

我有 3 個與產品相關的問題。首先，關於蘇珊娜的癌症。首先，關於 BYL。你能和我們分享一下你將如何定位產品嗎？它現在是具有重磅炸彈潛力的藥物的一部分。能否將其定位為 CDK 之後 Afinitor 之前的第二行？這方面的一些顏色會非常有幫助。第二個問題還是抗癌藥。關於 Kisqali，我認為您認為我們應該考慮 Kisqali 的銷售軌跡。什麼應該促進銷售和處方？是地域擴張、市場准入還是任何新的跡象？最後但同樣重要的是，關於 RTH 的快速問題。該申請從去年年底推遲到今年 2 月。我們必須明白這背後有什麼嗎？是否需要額外的數據或其他什麼？你能澄清一下嗎？

So first on BYL, Susanne.

首先是 BYL，Susanne。

Thanks, Florent. Thanks for the questions. So BYL, as we said, BYL has a potential to be the (inaudible) mutation patients. I mean, it's very hard to speculate about the label -- sorry, did you hear me or should I repeat? I'll go on. So it's hard to speculate about the label at this point. Obviously, there were data in SOLAR-1 suggesting there is positioning after CDK4. And as you might know, we have the BELIEVE trial running that should collect additional data in this setting. So we wait for the label, and then we can update you further on that. Maybe also on Kisqali. Actually, we are pleased with the uptake in 2018. Actually, Kisqali will remain a growth driver for oncology. And I think you mentioned where the safe trajectory will come from, and probably all 3 of that is correct, Florent. Actually, we saw increased momentum from the expansion of the indications into premenopausal patients, but also combinations with fulvestrant. As you know, we will be further rolling out in Europe and other markets. We see very strong uptake in emerging markets, and we also will see additional reimbursement achievement. So I think you mentioned the right 3 drivers to see increased trajectory.

謝謝，弗洛倫特。感謝您的提問。所以 BYL，正如我們所說，BYL 有可能成為（聽不清）突變患者。我的意思是，很難推測標籤——抱歉，你聽到我說的了嗎？還是我應該重複一遍？我會繼續。所以現在很難推測標籤。很明顯，SOLAR-1中有數據表明CDK4之後有定位。您可能知道，我們正在運行 BELIEVE 試驗，應該在此設置中收集更多數據。所以我們等待標籤，然後我們可以進一步更新你。也許也在 Kisqali 上。實際上，我們對 2018 年的採用情況感到滿意。實際上，Kisqali 仍將是腫瘤學的增長動力。我想你提到了安全軌蹟的來源，可能所有這三個都是正確的，Florent。實際上，我們看到適應症擴大到絕經前患者以及與氟維司群聯合使用的勢頭越來越大。如您所知，我們將在歐洲和其他市場進一步推廣。我們看到新興市場的接受度非常高，我們也將看到額外的報銷成就。所以我認為你提到了正確的 3 個驅動程序來看到增加的軌跡。

And on RTH, there is no new data requests. We are confident in the clinical package, the manufacturing package. And as we said, we plan to file with -- we expect next week with the priority review voucher and expect to launch in 2019. So no change or no new additions to our package.

而在 RTH 上，沒有新的數據請求。我們對臨床包、製造包充滿信心。正如我們所說，我們計劃提交——我們預計下週將提供優先審查憑證，並預計將於 2019 年推出。所以我們的包沒有變化或沒有新的添加。

The next question comes from the line of Seamus Fernandez from Guggenheim.

下一個問題來自古根海姆的 Seamus Fernandez。

Just wanted to get a quick update on some of the events that are coming this year. Wanted to get a little bit of an update on fevipiprant, the timing of data. And then also, just broadly speaking, as you guys are tracking the growth in the severe asthma market, particularly the eosinophil-driven severe asthma market, how is that market developing relative to your expectations? And what does that say for the opportunity for an oral drug in your thought processes? That's my only question.

只是想快速了解一下今年即將舉行的一些活動。想要獲得有關 fevipiprant 的一些更新，數據的時間。然後，從廣義上講，當你們正在追踪嚴重哮喘市場的增長，特別是嗜酸性粒細胞驅動的嚴重哮喘市場時，該市場相對於你們的預期如何發展？在您的思維過程中，這對口服藥物的機會有何影響？這是我唯一的問題。

Great. Thanks, Seamus. On the time lines, John?

偉大的。謝謝，西默斯。在時間線上，約翰？

Yes. As you noted earlier and as you heard through the presentation, we have a number of readouts this year, as you said, in fevipiprant. And we have the last patient in terms of our studies, ZEAL 1 and 2, that's fully recruited. We expect to read out that result in the second half of the year for fevipiprant. In addition to just fevipiprant, we also have COSENTYX for non-radiographic axial spondyloarthropathy on the PREVENT trial as well as ENTRESTO in heart failure with preserved ejection fraction. Not to mention -- in addition to that, also Zolgensma in the Type 2 SMA patients. So 2019 is a year full of data for us as we begin to read out that information throughout the year.

是的。正如您之前提到的以及您通過演示文稿聽到的那樣，正如您所說，我們今年有許多關於 fevipiprant 的讀數。就我們的研究而言，我們有最後一位患者，即 ZEAL 1 和 2，已全部招募。我們希望在今年下半年讀出 fevipiprant 的結果。除了 fevipiprant，在 PREVENT 試驗中我們還有用於非放射學中軸型脊柱關節病的 COSENTYX 以及用於射血分數保留的心力衰竭的 ENTRESTO。更不用說——除此之外，2 型 SMA 患者中的 Zolgensma 也是如此。所以 2019 年對我們來說是充滿數據的一年，因為我們開始全年讀出這些信息。

And I think we can provide greater clarity on time lines as we have a better sense of database locks, et cetera. So we'll keep the market informed. Now in terms of the market potential, Paul?

而且我認為我們可以在時間線上提供更清晰的信息，因為我們對數據庫鎖等有更好的認識。所以我們會隨時通知市場。現在就市場潛力而言，保羅？

So just one quick comment before fevipiprant. XOLAIR participates in that severe asthma population. It became a blockbuster in our territories. It is important to note the IgE approach is an alternate one to the IL-5 and we're very nicely positioned there. Question is really I think about the biologic space in general and what the market opportunity is for that. I think it's worth reminding ourselves that a lot depends on the readout and the tolerability and efficacy profile because if we get the right readout, our efficacy could be close to, if not equal to, the biologics IL-5, in particular. If our tolerability is good, then we would expect to move to the left in the treatment paradigm. And rather than worrying about the size of the severe asthma population, indeed, those treated with biologics, we will be in what we call the silent treatment gap. It's those struggling on high-dose inhaled therapies and not considered ready for biologics. That is about 3 million people we work out. So there is a very nice position, but it's very much going to depend on the profile of the medicine as it reads out, but that would be a good spot for us to be in.

所以在 fevipiprant 之前只有一個快速評論。XOLAIR 參與了該嚴重哮喘人群。它成為我們領土上的重磅炸彈。重要的是要注意 IgE 方法是 IL-5 的替代方法，我們在這方面的定位非常好。問題是我真的在考慮一般的生物空間以及它的市場機會是什麼。我認為值得提醒自己的是，很大程度上取決於讀數、耐受性和療效概況，因為如果我們得到正確的讀數，我們的療效可能接近（如果不等於）生物製劑 IL-5，尤其如此。如果我們的耐受性良好，那麼我們會期望在治療範式中向左移動。而不是擔心嚴重哮喘人口的規模，事實上，那些接受生物製劑治療的人，我們將處於我們所說的沉默治療差距。這是那些在大劑量吸入療法上苦苦掙扎並且尚未準備好使用生物製劑的人。那是我們鍛煉的大約300萬人。所以有一個非常好的位置，但這在很大程度上取決於藥物的概況，因為它讀出，但這對我們來說是一個很好的位置。

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

下一個問題來自 Jefferies 的 Peter Welford。

A couple of questions left, please. Firstly, on Zolgensma just with regard to the potential discussions with the regulators there. I appreciate you don't want to be specific, but just to understand more biologically and mechanistically, given the current administration route that you're following and also manufacturing constraint, are there any caps we should consider in terms of eligible populations that could be viable to get the drug before, obviously, the intrathecal formulation is available? Secondly then just on Sandoz. Curious in the near term, given you're talking obviously about reducing SKUs and making it an autonomous unit, should we be thinking about any dis-synergies potentially near term in the cost base of Sandoz, I guess, to make that an autonomous unit before obviously then we see the benefits through longer term? Or is that not likely to be the trend? And then just finally, just on crizanlizumab, just curious there with regards to the filings of any additional data being obtained in-house prior to this data you presented at the R&D Day? Or has this very much been a case of just compiling the data in a format that serves as applicable to the regulators?

請留下幾個問題。首先，關於 Zolgensma 與那裡監管機構的潛在討論。感謝您不想具體說明，只是為了從生物學和機制上更深入地了解，考慮到您目前遵循的給藥途徑以及製造限制，我們是否應該考慮符合條件的人群的上限明明之前拿藥可行，鞘內製劑可用嗎？其次，就在 Sandoz 上。在短期內很好奇，鑑於你顯然在談論減少 SKU 並使其成為一個自治單位，我想我們是否應該考慮 Sandoz 成本基礎中可能在短期內產生的任何協同效應，以使其成為一個自治單位顯然之前我們看到了長期的好處？或者這不太可能成為趨勢？最後，關於 crizanlizumab，您對在研發日提交的這些數據之前在內部獲得的任何其他數據的備案感到好奇嗎？或者這只是以適用於監管機構的格式編譯數據的情況？

So why don't we start with Sandoz on any dis-synergies or other implications of us moving to an autonomous approach?

那麼，為什麼我們不從 Sandoz 開始研究我們轉向自主方法的任何協同效應或其他影響呢？

I think -- thanks for the question. Peter, I think as -- Vas, you outlined earlier, when we did the integration, we believed there were synergies, and there indeed were. And we also found out as we executed, there were I think things we would call dis-synergies based on the model that we need to compete in a generics marketplace. I think to directly answer your question, we don't see any significant dis-synergies as we become more autonomous within Novartis. I do think we've got to be thoughtful and execute really well on extracting ourselves from that integration. But we've had some good plans. We've seen obviously what Alcon have done. So I think we've got a good methodology that we can follow. So we're not planning for that at this moment. We don't believe that's going to impact us and our ability to grow margins.

我想——謝謝你的提問。彼得，我認為——瓦斯，你之前概述過，當我們進行整合時，我們相信存在協同效應，而且確實存在。我們在執行過程中還發現，根據我們在仿製藥市場中競爭所需的模型，我認為我們會稱之為協同效應。我想直接回答你的問題，隨著我們在諾華內部變得更加自主，我們沒有看到任何重大的協同效應。我確實認為我們必須深思熟慮並執行得非常好，才能從這種整合中解脫出來。但我們有一些好的計劃。我們已經清楚地看到了愛爾康的所作所為。所以我認為我們有一個可以遵循的好方法。所以我們現在不打算這樣做。我們認為這不會影響我們和我們增加利潤的能力。

Great. Thanks, Richard. On Zolgensma and manufacturing capacity, Paul?

偉大的。謝謝，理查德。關於 Zolgensma 和製造能力，保羅？

So of course, we prepared very well for IV. In fact, we've started a significant amount of work in our second site in North Carolina. So we're going to be in very good shape. A little bit depends on the breadth of the label and the readout at AAN. If we can get to IT earlier, presents an opportunity for us both in patient population and of course in the amount of the therapy that we need to give. So we work all scenarios. You should expect it will be a little bit label-dependent, but we're positive that we can be prepared for whatever the need is that presents itself.

所以當然，我們為 IV 準備得很好。事實上，我們已經在北卡羅來納州的第二個站點開展了大量工作。所以我們的狀態會很好。一點點取決於標籤的寬度和 AAN 的讀數。如果我們能更早地接觸到 IT，那麼無論是在患者群體中，還是在我們需要提供的治療量方面，都為我們提供了機會。所以我們處理所有場景。你應該預料到它會有點依賴於標籤，但我們確信我們可以為出現的任何需求做好準備。

Great, Paul. And then crizanlizumab?

太好了，保羅。然後crizanlizumab？

Yes. Lastly, on crizanlizumab, Peter. As you know, we showed the results of our Phase II SUSTAIN trial that showed that we had a reduction of 45% in terms of the annual rate of sickle pain crises or vaso-occlusive crises. And we received the breakthrough designation in December with the FDA. And in fact, that's moving forward, and we intend to file in the first quarter of this year. So that's advancing well.

是的。最後，關於 crizanlizumab，Peter。如您所知，我們展示了我們的 II 期 SUSTAIN 試驗的結果，該試驗表明我們的鐮狀痛危像或血管閉塞性危象的年發生率降低了 45%。我們在 12 月獲得了 FDA 的突破性認定。事實上，這正在向前推進，我們打算在今年第一季度提交文件。所以進展順利。

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

下一個問題來自 Cowen 的 Steve Scala。

I have a few questions. First, is generic Advair still expected to be launched by the end of the year? I ask because it wasn't on Slide 15. Second, do you know the results of the AVXS 101 STRONG and SPRINT studies now? I'm curious how you know that Type 1 predicts Type 2 and 3. And then lastly, what percent of metastatic breast cancer market in the U.S. do you think has already been penetrated by CDK 4/6 inhibitors? I ask because I thought companies had been saying it was 60%, 70% or even more, but yesterday, Pfizer said 50%. So I'm just curious what you think that percentage is.

我有幾個問題。首先，仿製藥 Advair 是否仍有望在年底前推出？我問是因為它不在幻燈片 15 上。第二，你現在知道AVXS 101 STRONG和SPRINT研究的結果了嗎？我很好奇你怎麼知道 1 型預測 2 型和 3 型。最後，你認為美國有多少轉移性乳腺癌市場已經被 CDK 4/6 抑製劑滲透？我問是因為我認為公司一直在說它是 60%、70% 甚至更多，但昨天，輝瑞公司說是 50%。所以我很好奇你認為這個百分比是多少。

So first on generic Advair, Richard?

那麼首先是通用的 Advair，理查德？

Thanks for the question, Steve So we do aim to file the product this year. We are sort of forecasting that we do believe that's going to be in early 2020. As you said, it was 2019, and it still is a possibility based on the time lines of the FDA and the broad window they give. I think we're -- maybe we're looking at that a bit more conservatively, hence the reason why we say 2020 now.

謝謝你的問題，史蒂夫 所以我們的目標是今年提交產品。我們的預測是，我們相信這將在 2020 年初實現。正如您所說，那是 2019 年，根據 FDA 的時間表和他們提供的廣泛窗口，這仍然是一種可能性。我認為我們 - 也許我們正在更保守地看待這個問題，因此我們現在說 2020 年的原因。

So on -- thank you, Richard. On AVXS-101, just briefly, we -- the studies are open-label studies. So there's a group of us that of course are understanding how the results are evolving. But really, our comments were driven by what we overall expect from a biologics standpoint, that is strong performance and SMA Type 1 should enable strong performance in SMA 2, 3. And we look forward to providing the full update at AAN in May. And then, Susanne, on the metastatic breast cancer penetration...

等等——謝謝你，理查德。關於 AVXS-101，簡單地說，我們——這些研究是開放標籤研究。所以我們中有一群人當然正在了解結果是如何演變的。但實際上，我們的評論是由我們從生物製劑角度的總體預期驅動的，即強大的性能和 SMA 1 型應該能夠在 SMA 2、3 中實現強大的性能。我們期待在 5 月份的 AAN 上提供完整的更新。然後，Susanne，關於轉移性乳腺癌的滲透……

(inaudible)

（聽不清）

So 60%, Steve, is what we have -- but we of course defer to our colleagues at Pfizer if they have better figures.

所以 60%，史蒂夫，就是我們所擁有的——但如果輝瑞的同事有更好的數字，我們當然會服從他們。

The next question comes from the line of David Evans from Kepler Cheuvreux.

下一個問題來自 Kepler Cheuvreux 的 David Evans。

Just thinking a little longer term. As you've done your R&D budgeting for year, just amongst your combined new platforms of cell, gene therapy, radioligands, beyond the first wave of marketed on near-term opportunities, can you give us a sense of which other earlier-stage programs you're most optimistic on and perhaps where you're directing increased funding to progress those quicker?

只是考慮更長遠一點。當你完成一年的研發預算時，就在你的細胞、基因治療、放射配體的組合新平台中，除了第一波近期機會營銷之外，你能告訴我們還有哪些其他早期項目嗎您最樂觀的是，也許您將增加資金用於更快地取得進展？

Yes. So Jay is not here, but maybe I'll just give a high level of kind of where we're focused on. On gene therapy, we're focused on actually a pretty broad platform of internal programs as well as looking externally, primarily in neuroscience, in ophthalmology and in nonmalignant hematology, I think are the big areas of focus. But, of course, we're open to other areas. And that's a combination of internal programs in our research unit in NIBR as well as what's happening at AveXis. In cell therapy or in lentiviral-based therapies, we have a big focus on the next wave of innovation in CAR, so trying to get to more rapid manufacturing, more high-affinity CARs, bi-specific CARs. So I'll hold that the next wave of technology, I'd say I'm most interested to see how our rapid manufacturing evolves. That has I think the potential to truly transform our overall approach in the area. And actually on radioligand therapy, Susanne can comment. She ran the unit. But in terms of earlier-stage assets, what would you say, Susanne?

是的。所以傑伊不在這裡，但也許我會高水平地介紹一下我們關注的地方。在基因治療方面，我們實際上專注於一個相當廣泛的內部項目平台，同時也關注外部，主要是神經科學、眼科和非惡性血液學，我認為這是重點關注的領域。但是，當然，我們對其他領域持開放態度。這是我們在 NIBR 研究部門的內部項目以及 AveXis 正在發生的事情的結合。在細胞療法或基於慢病毒的療法中，我們非常關注 CAR 的下一波創新，因此試圖實現更快的製造、更高親和力的 CAR、雙特異性 CAR。所以我認為下一波技術浪潮，我想說我最感興趣的是看看我們的快速製造是如何發展的。我認為這有可能真正改變我們在該領域的整體方法。實際上，關於放射配體療法，Susanne 可以發表評論。她負責這個單位。但就早期資產而言，蘇珊娜，你怎麼看？

Yes. As I said, there's 3 assets that have entered Phase I. But I think what -- the affinity between NIBR and AAA I think would also leave us aspiring that there's new targets that we can define. So we are working on that, and we update you in due course.

是的。正如我所說，有 3 項資產已進入第一階段。但我認為——我認為 NIBR 和 AAA 之間的親和力也會讓我們渴望有我們可以定義的新目標。所以我們正在努力，我們會在適當的時候向您更新。

I mean, the power of the radioligand therapy platform is that if we can find a antigen that is taken up by -- with a high affinity in target tumor types. And then all we need to do -- and if it's got enough specificity, if we can link it then with the radioactive particle, we have a drug. And so we believe this platform is something we can apply to, hopefully, multiple assets we have within our NIBR portfolio to take on a range of solid tumors. So that gives you a little bit of a high level of where we're at.

我的意思是，放射配體治療平台的力量在於，如果我們能夠找到一種被吸收的抗原——在目標腫瘤類型中具有高親和力。然後我們需要做的就是——如果它有足夠的特異性，如果我們可以將它與放射性粒子聯繫起來，我們就有了一種藥物。因此，我們相信這個平台是我們可以應用的東西，希望我們在 NIBR 產品組合中擁有多種資產，以應對一系列實體瘤。所以這讓你對我們所處的位置有了一點了解。

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

下一個問題來自瑞銀的 Michael Leuchten。

One for Harry, one for Susanne and one for Paul, please. Just, Harry, going back to the guidance, I'm trying to square why the guidance, both current group structure and under the new structure, do include one scenario where there isn't any margin guidance. I was wondering how that's possible given the efficiency programs that you're talking about, what's growing, especially in -- under the new structure. Second question for Susanne. On SEG101, do you need additional infrastructure to position a product? Or is the indication or potential indication close enough to the existing infrastructure so you can leverage it? And then question for Paul. I think your punchline previously for COSENTYX was clear is clear, and I think in your remarks you said something like it takes more than clear skin to win. So is there a change in positioning of the product on the ground in the U.S. on the back of the data that we've seen recently? Or is it just a different way to talk about it?

請給哈里一份，給蘇珊娜一份，給保羅一份。只是，哈利，回到指導，我試圖弄清為什麼指導，包括當前的集團結構和新結構，確實包括一個沒有任何保證金指導的場景。我想知道，考慮到您正在談論的效率計劃，以及正在增長的東西，尤其是在新結構下，這怎麼可能。蘇珊娜的第二個問題。在 SEG101 上，您是否需要額外的基礎設施來定位產品？或者指示或潛在指示是否足夠接近現有基礎設施以便您可以利用它？然後向保羅提問。我認為您之前對 COSENTYX 的妙語很明確，而且我認為在您的評論中您說過類似的話，要贏得勝利需要的不僅僅是皮膚清晰。那麼，根據我們最近看到的數據，產品在美國的定位是否發生了變化？或者這只是一種不同的談論方式？

Thank you. So first, Harry, on the guidance.

謝謝。所以首先，哈利，關於指導。

[Let me show you.] We expect to expand core margin in any of the scenarios, either current group structure or new focused company. So that's why I mentioned also in my comments we clearly expect core operating income in constant currency to grow ahead of sales and improve margin. So there's no, from my standpoint, scenario where that wouldn't happen. So strong expectation internally and strong will to drive these productivity programs and strong launches to expand the margin.

[讓我告訴你。]我們希望在任何情況下擴大核心利潤率，無論是當前的集團結構還是新的重點公司。因此，這就是為什麼我在評論中也提到我們明確預計以固定匯率計算的核心營業收入將在銷售額之前增長並提高利潤率。因此，從我的角度來看，不存在這種情況不會發生的情況。如此強烈的內部期望和強烈的意願將推動這些生產力計劃和強大的啟動以擴大利潤率。

Thank you, Harry. Susanne, on SEG101?

謝謝你，哈利。蘇珊娜，在 SEG101 上？

Yes, Michael, thanks for the question. As you know, we have a footprint from Exjade, but that is going off patent. And so therefore, we know the customer base quite well. I mean, for SEG101, this will be a very targeted launch. And there, we need some dedicated resources, but this is based on the current footprint.

是的，邁克爾，謝謝你的提問。如您所知，我們有 Exjade 的足跡，但那是專利過期。因此，我們非常了解客戶群。我的意思是，對於 SEG101，這將是一次非常有針對性的發布。在那裡，我們需要一些專用資源，但這是基於當前的足跡。

Great, Susanne. And then lastly, on skin to win, Paul?

太好了，蘇珊娜。最後，在皮膚上取勝，保羅？

So I'm delighted people listen so intently to my comments. But -- so let's just remind ourselves. I think we said the efficacy bar in psoriasis has been reached, and that we set that standard. And we don't think it needs to go beyond that. It was in specific relation to PASI. We feel very good. My comment on it's more than a skin to win is basically about the extra manifestations. It's about those patients that isn't just skin, that have nail, joint, scalp, et cetera, involvement. And in those patients, we really do need to demonstrate our effectiveness. Now we're out there and doing it with indications on long-term data. We set a high bar there as well, so forgive me for confusing, but psoriasis, we're in a good place. And we think we are perhaps in equally good place in (inaudible).

所以我很高興人們如此專注地傾聽我的評論。但是——讓我們提醒自己。我想我們說過銀屑病的療效標準已經達到，我們設定了這個標準。而且我們認為它不需要超出此範圍。它與 PASI 有特定關係。我們感覺很好。我對它的評論不僅僅是要贏的皮膚，基本上是關於額外的表現形式。這是關於那些不僅僅是皮膚，還有指甲、關節、頭皮等受累的患者。在這些患者身上，我們確實需要證明我們的有效性。現在我們在那裡並根據長期數據的指示來做這件事。我們也在那裡設置了一個高標準，所以請原諒我的混淆，但牛皮癬，我們處在一個好地方。我們認為我們可能在（聽不清）中處於同樣好的位置。

The next question comes from the line of Ronny Gal from Bernstein.

下一個問題來自 Bernstein 的 Ronny Gal。

I have 2, if you don't mind. First, could you give us a little bit update about your Copaxone generic glatiramer acetate in terms of capacity and manufacturing ability to commercialize the product in the United States? And second, now as you're thinking about separation of the -- essentially the generic business unit, how do you think about the operating margin of [kind of like a] biosimilar-focused business long term? So once this unit is stabilized and -- or at least that part of it which is biosimilars long term. Given the current pricing trend in Europe, where should we see the operating margin of business like this?

我有2個，如果你不介意的話。首先，您能否就您的 Copaxone 仿製藥醋酸格拉替雷在美國商業化的能力和製造能力向我們介紹一些最新情況？其次，現在當你考慮分離 - 本質上是通用業務部門時，你如何看待[有點像]以生物仿製藥為重點的業務的長期營業利潤率？因此，一旦這個單位穩定下來，或者至少是長期生物仿製藥的那一部分。鑑於歐洲目前的定價趨勢，我們應該在哪裡看到這樣的業務的營業利潤率？

Thanks, Ronny, and nice to hear from you. On Copaxone, Richard, do you want to provide the update?

謝謝，羅尼，很高興收到你的來信。關於 Copaxone，理查德，你想提供更新嗎？

Yes. Thanks, Vas. Ronny, see, on Copaxone, so let me talk about it both on 20 milligrams and 40 milligrams. I think on 20 milligrams, obviously we saw competition come into it last year. I think I've been very pleased about how we've actually defended our business there with thoughtful pricing, but we pretty much kept our market share slightly stable, so pleased with the team with how they've done that. On the 40 milligrams, as you know, we had a slower start to that last year based on production. And now we've started to go out and actually win some contracts and some business. So I think you'll see that starting to pick up. And we have the production to meet the business we've won and contracted for. And I think you'll see on NRx that we've started to actually grow NRx on the 40 milligrams. I would say, on the 40 milligrams, this is an opportunity, but I think it's one that's going to be similar to 20 when we started out on that journey. It's going to take a bit of time to penetrate, but we still think it's an attractive market, so we are focused on it. With regard to the...

是的。謝謝，瓦斯。羅尼，看，關於 Copaxone，所以讓我談談 20 毫克和 40 毫克。我認為在 20 毫克上，顯然我們去年看到了競爭。我想我對我們如何以周到的定價實際上捍衛我們在那裡的業務感到非常高興，但我們幾乎保持了我們的市場份額略微穩定，對團隊如何做到這一點感到非常滿意。如您所知，在 40 毫克的基礎上，我們去年的起步較慢。現在我們已經開始走出去，實際上贏得了一些合同和一些業務。所以我想你會看到它開始回升。我們的生產可以滿足我們贏得和承包的業務。而且我想你會在 NRx 上看到我們已經開始在 40 毫克上實際種植 NRx。我會說，在 40 毫克上，這是一個機會，但我認為這將與我們開始那段旅程時的 20 毫克相似。滲透需要一些時間，但我們仍然認為這是一個有吸引力的市場，所以我們專注於它。關於...

Biosimilar margins.

生物仿製藥利潤率。

Yes, biosimilar margins. Yes, we're very pleased with the biosimilar margins as they are now. I think your question was more about how do I think these are going to be going forward with the pricing in the market? I mean, there's 2 things I'd say, is if you look at our base business in biosimilars, they -- particularly in Europe, which some of those are 10 years old, those are still growing at double digit on sales. So I think it just shows that if you have the right structure behind them, you can make these assets continue to grow over time. That said, we are very focused on cost of goods and making sure we have a lean TSE structure in the anticipation that the pricing will come down. But all of those things together make me believe that the biosimilar margin will -- and return on sales will continue to grow over the short to midterm. I haven't really looked a lot beyond that because other thing we're doing is adding to our portfolio, obviously the Biocon; our own internal development, which is full; as well as Gan & Lee. So we're going to have a very broad portfolio, which we're going to lay on top of our existing commercial infrastructure, which gives us a nice synergistic play, which makes me believe the margins will stay -- will be growing and stay high.

是的，生物仿製藥利潤率。是的，我們對現在的生物仿製藥利潤率感到非常滿意。我認為您的問題更多是關於我認為這些將如何隨著市場定價而發展？我的意思是，我要說兩件事，如果你看看我們在生物仿製藥方面的基礎業務，它們——特別是在歐洲，其中一些已經有 10 年曆史了，它們的銷售額仍在以兩位數的速度增長。所以我認為這只是表明，如果你在它們背後有正確的結構，你可以讓這些資產隨著時間的推移繼續增長。也就是說，我們非常關注商品成本，並確保我們有一個精簡的 TSE 結構，因為預計價格會下降。但所有這些因素加在一起讓我相信，生物仿製藥的利潤率和銷售回報率將在中短期內繼續增長。除此之外，我並沒有真正看到太多，因為我們正在做的其他事情是增加我們的產品組合，顯然是 Biocon；我們自己的內部發展，這是完整的；以及甘李。所以我們將擁有一個非常廣泛的產品組合，我們將把它放在我們現有的商業基礎設施之上，這給了我們一個很好的協同作用，這讓我相信利潤率會保持——會增長並保持高的。

Next question comes from the line of Mark Purcell from Morgan Stanley.

下一個問題來自摩根士丹利的 Mark Purcell。

Firstly, on the manufacturing network and innovation -- Innovative Medicines. Please could you discuss where you are in respect to capacity across the different divisions? You've given us some color on cellular therapy, less so in terms of gene and radiotherapy. Where you are and where you're aiming to be in terms of capacity? And can you get there organically? Or will bolt-on acquisitions be a key component of your aspirations when it comes to scale? And separately, on Sandoz, could you help us understand the overlap in manufacturing between IM and Sandoz at the moment? Secondly, I'd just like to understand your expectation currently and also the range of expectations for ENTRESTO generic launches in the United States from a timing perspective. Number three, on U.S. net pricing, you've given a top line guidance. But could you help us understand which products are the most important in terms of the drags and how that changes moving into '19 from '18? And then just lastly, for Paul, could the TIK 2 approach in psoriasis be to IL-17s and 23s what you hope fevipiprant could be to the biologic -- injectable biosimilar drugs currently on the market?

首先，關於製造網絡和創新——創新藥物。請您討論一下您在不同部門的產能方面所處的位置？你給了我們一些關於細胞療法的色彩，但在基因和放射療法方面的色彩較少。就能力而言，你在哪里以及你的目標是什麼？你能有機地到達那裡嗎？或者，在擴大規模方面，補強收購是否會成為您實現抱負的關鍵組成部分？另外，關於 Sandoz，您能否幫助我們了解目前 IM 和 Sandoz 在製造方面的重疊？其次，我只想從時間的角度了解您目前的期望以及對 ENTRESTO 仿製藥在美國上市的期望範圍。第三，關於美國淨定價，你已經給出了頂線指導。但是您能否幫助我們了解哪些產品在阻力方面最重要，以及從 18 年到 19 年的變化如何？最後，對 Paul 來說，TIK 2 治療銀屑病的方法對 IL-17s 和 23s 的影響是否與您希望 fevipiprant 對目前市場上的生物注射生物仿製藥的影響一樣？

All right. So first, I'll take the manufacturing questions in the interest of time. And in gene therapy, we have our plant in Chicago, which is our launch facility. We've already invested in a plant in North Carolina, where we've approved doubling the capacity of that facility, and we're currently evaluating building out capacity in Europe. We feel confident that in our AAV platform, AAV9, but also other AAVs, we believe we'll have adequate capacity in the near term and then, over time, we'll have adequate capacity. Given that these indications are not huge numbers of patients, we think we will be well placed. In cell therapy, you heard from Susanne, we have a significant capacity expansion ongoing. And then I think we'll have a substantial global capacity to do cell processing, primarily lentiviral-based cell processing, but also in the future if there are nonviral-based cell processing approaches, we can certainly use those as well. And then in terms of radioligand therapy, AAA has I think a very strong network already in Europe and the U.S., but we are evaluating expanding that network as we prepare for the potential prostate cancer. And then if we were to move into another solid tumors, the solid tumors you saw listed, we would need, of course, a significant capacity expansion. Some of those might involve partnerships or external moves in the case of radioligand therapy, but we're evaluating those currently. Now with respect to the manufacturing overlap today between Innovative Medicines and Sandoz, there's 2 principal places of overlap: one is packaging, where it's also easy to dis-intermediate the overlap, that's the -- a key area of overlap at the moment; and the other is in biologics production, where the same plants do cover COSENTYX, Alaris and other parts of our Innovative Medicines portfolio as cover our biosimilars. And so -- but we believe we can manage that through supply agreement internally once we move to the separated state. So in terms of ENTRESTO generic launches, Paul, any updates on that front?

好的。所以首先，為了節省時間，我將回答製造問題。在基因治療方面，我們在芝加哥設有工廠，這是我們的發射設施。我們已經在北卡羅來納州投資了一家工廠，我們已經批准將該工廠的產能提高一倍，目前我們正在評估在歐洲擴建產能。我們有信心在我們的 AAV 平台 AAV9 以及其他 AAV 中，我們相信我們將在短期內擁有足夠的容量，然後隨著時間的推移，我們將擁有足夠的容量。鑑於這些適應症不是大量的患者，我們認為我們將處於有利地位。在細胞療法方面，您從 Susanne 那裡聽說，我們正在進行顯著的產能擴張。然後我認為我們將擁有強大的全球能力來進行細胞處理，主要是基於慢病毒的細胞處理，但在未來如果有基於非病毒的細胞處理方法，我們當然也可以使用它們。然後在放射配體治療方面，我認為 AAA 在歐洲和美國已經有一個非常強大的網絡，但我們正在評估擴大該網絡，因為我們為潛在的前列腺癌做準備。然後，如果我們要進入另一個實體腫瘤，你看到列出的實體腫瘤，我們當然需要顯著的產能擴張。在放射配體治療的情況下，其中一些可能涉及合作夥伴關係或外部行動，但我們目前正在評估這些。關於今天 Innovative Medicines 和 Sandoz 之間的製造重疊，有兩個主要的重疊地方：一個是包裝，在那裡也很容易消除重疊，這是目前重疊的一個關鍵領域；另一個是生物製劑生產，同樣的工廠也涵蓋了 COSENTYX、Alaris 和我們創新藥物產品組合的其他部分，就像我們的生物仿製藥一樣。所以——但我們相信，一旦我們轉移到分離狀態，我們就可以通過內部供應協議來管理這一點。那麼就 ENTRESTO 仿製藥的推出而言，Paul，這方面有什麼更新嗎？

So -- and I'm not sure I got the question entirely, but I would just make the point that in all major markets, we feel very good about the IP and where we stand. There's always some small bits and pieces around, but nothing that has any material impact to our overall guidance for the long term.

所以——我不確定我是否完全理解了這個問題，但我只想指出，在所有主要市場中，我們對 IP 和我們所處的位置感覺非常好。總會有一些小細節，但不會對我們的長期整體指導產生任何實質性影響。

Yes. So in U.S., no change in our guidance in terms of the patent protection for ENTRESTO or the exclusive -- market exclusivity for ENTRESTO. Now in terms of net pricing, I think your question was are there particular products where we have higher exposure to net pricing dynamics? I think, as you've heard from Paul, we have a stabilizing situation in general with COSENTYX and ENTRESTO. But almost every medicine we have in our Innovative Medicines portfolio has some level of rebating. And overall, we -- as I've said, I think on a few occasions, we expect to see net prices decline in the U.S. for us in our Innovative Medicines portfolio in the low single-digit range. We wouldn't break out individual products per se, but I can say that rebating at this point is broad-based within the pharmaceuticals portfolio, and we do see it starting to come into oncology as well in certain therapy lines. So rebate levels are much lower in oncology, but we do see them happening every year more and more. So that of course is also leading to a dynamic on our overall net pricing. I think the last question was on the TIK 2 approach as an alternative to COSENTYX. So John, do you want to take that? Maybe, John, you'd have...

是的。因此在美國，我們在 ENTRESTO 的專利保護或獨家市場排他性方面的指導沒有變化。現在就淨定價而言，我想你的問題是，是否存在我們對淨定價動態有更高風險的特定產品？我認為，正如你從 Paul 那裡聽到的那樣，我們的 COSENTYX 和 ENTRESTO 總體上處於穩定狀態。但我們的創新藥物組合中幾乎所有藥物都有一定程度的回扣。總的來說，我們 - 正如我所說，我認為有幾次，我們預計我們的創新藥物產品組合在美國的淨價格將下降至低個位數範圍。我們不會單獨列出個別產品，但我可以說，此時的回扣在藥品組合中是廣泛存在的，我們確實看到它開始進入腫瘤學以及某些治療領域。因此，腫瘤學的回扣水平要低得多，但我們確實看到它們每年都在越來越多地發生。因此，這當然也會導致我們整體淨定價的動態變化。我認為最後一個問題是關於 TIK 2 方法作為 COSENTYX 的替代方法。約翰，你想接受嗎？也許，約翰，你會...

Yes. Sure. As you know, for COSENTYX, we have the indications for psoriasis, psoriatic arthritis and ankylosing spondylitis. I think TIK 2 currently is entering into Phase III. They are looking at dermatologic manifestations. So I think it's early, and it's too -- we try not to speculate on other mechanisms.

是的。當然。如您所知，對於 COSENTYX，我們有銀屑病、銀屑病關節炎和強直性脊柱炎的適應症。我認為 TIK 2 目前正在進入第三階段。他們正在研究皮膚病學表現。所以我認為現在還為時過早——我們盡量不去推測其他機制。

And I think Paul also has a...

我認為保羅也有...

Yes, just because it was -- the question was also related to the approach of fevipiprant I think in the original question, we've made some very sensible choices around fevi. So -- and as I alluded to in my answers earlier, we're setting a standard of efficacy up with biologics, but we hope to have a tolerability profile that puts us in this silent treatment gap. Be interested to see choices made by those looking after TIK 2s, whether they go after the efficacy and run the risk of a compromised safety profile or whether they position themselves as less and less. So we're vigilant as always, but we do believe in the end, the monoclonal antibody COSENTYX will come out in the lead.

是的，只是因為它 - 這個問題也與我認為在原始問題中的 fevipiprant 方法有關，我們圍繞 fevi 做出了一些非常明智的選擇。所以——正如我之前在回答中提到的那樣，我們正在製定生物製劑的療效標準，但我們希望有一個耐受性概況，使我們處於這種沉默的治療差距中。有興趣看看那些關注 TIK 2 的人做出的選擇，他們是否追求療效並冒著安全性受損的風險，或者他們是否將自己定位為越來越低。所以我們一如既往地保持警惕，但我們相信最終單克隆抗體COSENTYX會拔得頭籌。

The next question comes from the line of Kerry Holford from Exane BNP Paribas.

下一個問題來自 Exane BNP Paribas 的 Kerry Holford。

Yes, it's Kerry Holford from Exane. Just one question left for me, please, on Aimovig. I wondered if you can just give us an update on the ex U.S. rollout, in which countries have you now launched and secured reimbursement? And in the U.S., we've saw obviously that CVS announced it would not cover Aimovig in favor of Lilly and Teva's products. So I would just like to know whether you played a role in those formulary negotiations in the U.S.? Or was that entirely run by your partner? And if you were involved, what were the sole processes behind those negotiations? Was it simply a question of the highest rebate wins?

是的，我是來自 Exane 的 Kerry Holford。請留給我一個關於 Aimovig 的問題。我想知道您是否可以向我們介紹一下美國前推出的最新情況，您現在在哪些國家/地區推出並獲得了報銷？在美國，我們已經清楚地看到 CVS 宣布它不會覆蓋 Aimovig 以支持 Lilly 和 Teva 的產品。所以我想知道你是否在美國的那些公式化談判中發揮了作用？還是完全由您的合作夥伴經營？如果您參與其中，這些談判背後的唯一流程是什麼？這只是一個最高返利獲勝的問題嗎？

So, Paul, 2 questions on Aimovig EU rollout and reimbursement discussions and then on our role in the formulary discussions in the U.S.

所以，保羅，關於 Aimovig 歐盟推出和報銷討論的 2 個問題，然後是關於我們在美國處方集討論中的作用

So we're pretty much at the beginning in Europe, approval followed by rolling reimbursement. As you know, it takes a bit of time to get all of the major European markets where we hope they would be, and we're in those conversations right now. I can tell you the unprecedented, unmet need for those taking the out-of-pocket route shows the demand that we saw in the U.S. is likely to manifest itself in Europe and the other markets. So we think we'll be equally well positioned there. Amgen of course take the lead on access and pricing in the United States, and so that's perhaps a question better left to them. But in the spirit of -- we work through a lot of things together, we have very good access in the U.S., and we -- I'm not sure it's been shared or whether we shared on the Amgen call, but it's worth noting, given the amount of free drug and no paperwork being offered by competition, we have a slightly artificial environment at the moment that will settle down in terms of NBRx share in Europe -- sorry, in the U.S. But the number of paid prescriptions for Aimovig in the U.S. has climbed in Q3 from 35% to Q4 50%. So the -- so trying to run a sensible business will win the day, and we look forward to things settling down in the U.S.

所以我們在歐洲幾乎處於起步階段，先是批准，然後是滾動報銷。如您所知，要讓所有主要的歐洲市場都達到我們希望的水平需要一些時間，而我們現在正在進行這些對話。我可以告訴你，對於那些採取自付費用的人來說，前所未有的、未滿足的需求表明我們在美國看到的需求很可能會在歐洲和其他市場表現出來。所以我們認為我們在那裡同樣處於有利地位。Amgen 當然在美國的准入和定價方面處於領先地位，所以這個問題最好留給他們。但本著——我們一起完成很多事情的精神，我們在美國有很好的訪問權限，而且我們——我不確定它是否被共享或者我們是否在 Amgen 電話會議上共享，但值得注意的是，考慮到免費藥物的數量並且沒有競爭提供的文書工作，我們目前有一個稍微人為的環境，它將在歐洲的 NBRx 份額方面穩定下來——抱歉，在美國，但是 Aimovig 的付費處方數量在美國，第三季度從 35% 攀升至第四季度的 50%。所以——所以努力經營一個明智的企業將贏得勝利，我們期待在美國安定下來。

The next question comes from the line of Naresh Chouhan from Intrinsic Health.

下一個問題來自 Intrinsic Health 的 Naresh Chouhan。

Just one on ENTRESTO. The scripts look like they are accelerating. So some help in trying to understand what's driving that. Is that the PIONEER data? Or has there been some additional rebates that's driven that volume? And then you've obviously laid out the extent of the manufacturing capacity that's being added based on cell and gene therapy. So how should we think about CapEx over the next few years? And has that [lightness] increased materially? Or are we expecting the similar levels over the next few years?

只有一個在 ENTRESTO 上。腳本看起來正在加速。所以一些幫助試圖理解是什麼在推動它。那是PIONEER的數據嗎？還是有一些額外的回扣推動了這一銷量？然後你顯然已經列出了基於細胞和基因療法而增加的製造能力的範圍。那麼我們應該如何考慮未來幾年的資本支出呢？那[亮度]有沒有實質性地增加？還是我們預計未來幾年會出現類似的水平？

So first, ENTRESTO, Paul?

首先，ENTRESTO，保羅？

So thank you. There has been a modest acceleration. We're not declaring victory because, as I mentioned earlier on, there are some systems in the U.S. and there's 1 or 2 major European markets that have decided to go very quickly based on PIONEER data because of what it means for patients and how it reduces the overall readmission costs frankly in health systems. But we have some work to do to industrialize that, the length and breadth of the major markets. So whilst we're pleased with the effort, we'll continue to climb. That is our expectation through the year and beyond and through PARAGON and beyond.

所以謝謝。出現了適度的加速。我們並沒有宣布勝利，因為正如我之前提到的，美國有一些系統，並且有 1 或 2 個主要歐洲市場決定根據 PIONEER 數據快速發展，因為它對患者意味著什麼以及它如何坦率地說，降低了衛生系統的整體再入院成本。但我們還有一些工作要做，以實現主要市場的長度和廣度的工業化。因此，儘管我們對所做的努力感到滿意，但我們將繼續攀登。這是我們今年及以後以及 PARAGON 及以後的期望。

And in terms of CapEx, Harry?

就資本支出而言，哈利？

Naresh, so on CapEx, as you know, over a few years back, we were at 5% plus of sales. We brought that down via focus and then manufacturing footprint work, capacity utilization increases to a range of 3.5%. So last year 3.5% in 2017; 3.4% of sales in 2018. And we expect the CapEx to be a bit fluctuating, but in the 3% to 4% range. So nothing material due to the new platforms.

Naresh，所以在資本支出方面，如你所知，幾年前，我們的銷售額增加了 5%。我們通過重點和製造足跡工作降低了這一點，產能利用率增加到 3.5% 的範圍。所以去年2017年是3.5%；佔 2018 年銷售額的 3.4%。我們預計資本支出會有所波動，但在 3% 至 4% 的範圍內。因此，由於新平台，沒有什麼實質性的。

Thanks, Harry. Last question. Go ahead, please?

謝謝，哈利。最後一個問題。請繼續，好嗎？

Next question comes from the line of Marietta Miemietz from Primavenue.

下一個問題來自 Primavenue 的 Marietta Miemietz。

I have a couple, please. One is on the midterm margins. How much of the $2 billion in savings targeted by 2020 have been achieved? And how fast do you think you can come up with a new program that will be somewhat similar in scope, maybe another $1 billion to $2 billion in savings? And more importantly, maybe at the Q2 stage, you hinted that you might upgrade your midterm pharma margin target as and when you have more visibility on Gilenya LOE. And now you're basically giving short-term guidance, excluding the Gilenya generic, but the pharma margin target has stayed the same. So I'm just wondering, are you basically looking to update the midterm pharma margin target later this year or early next year when some of the things Shannon mentioned have panned out? Or is there something else that's holding you back? And the second question is on Sandoz. When you say it's becoming autonomous without any dis-synergies, is that literally just talking about in vivo carve-out? Or is there actually more to it operationally? And could you elaborate a little bit please on the strategy for the insulin biosimilars and how big that potentially -- could potentially become? I mean, I was just a little bit surprised to see you enter that space because the previous management team basically said a number of years back that they wouldn't touch insulin biosimilars with a barge pole because it was much lower margins than other biosimilars and you needed massive scale to compete. And I think if anything, the insulin space seems to have become a lot more competitive since then. So what has actually changed? Has the access to the very low-cost insulin by Gan & Lee changed the economics? And can you give us a rough idea of the gross margin? Or is it just that the going in biosimilars and generics is so tough that now insulins are looking better on a relative basis? Or are you simply aiming for -- are you actually aiming for significant market share? Or is that really just something that completes your portfolio of affordable medicines as part of your ESG efforts? So any color there would be helpful.

我有一對，請。一個是中期利潤率。到 2020 年節省 20 億美元的目標中有多少已經實現？您認為您能以多快的速度提出一個在範圍上有些相似的新計劃，也許還能節省 10 億到 20 億美元？更重要的是，也許在第二季度階段，你暗示你可能會在你對 Gilenya LOE 有更多了解時升級你的中期製藥利潤率目標。現在你基本上是在提供短期指導，不包括 Gilenya 仿製藥，但製藥利潤率目標保持不變。所以我只是想知道，當 Shannon 提到的一些事情已經實現時，你是否基本上希望在今年晚些時候或明年初更新中期製藥利潤率目標？還是有其他事情阻礙了你？第二個問題是關於山德士的。當你說它在沒有任何協同作用的情況下變得自主時，這真的只是在談論體內分拆嗎？或者實際上還有更多的操作？您能否詳細說明一下胰島素生物仿製藥的策略以及它的潛力有多大？我的意思是，看到你進入那個領域我有點驚訝，因為之前的管理團隊基本上在幾年前說過他們不會用駁船桿接觸胰島素生物仿製藥，因為它的利潤率比其他生物仿製藥低得多，而且你需要大規模才能競爭。而且我認為，從那時起，胰島素領域似乎變得更具競爭力。那麼究竟發生了什麼變化呢？甘李公司獲得成本極低的胰島素是否改變了經濟學？你能給我們一個大概的毛利率嗎？或者僅僅是因為生物仿製藥和仿製藥的發展如此艱難，以至於現在胰島素在相對基礎上看起來更好？或者你只是想——你真的想獲得顯著的市場份額嗎？或者這真的只是作為 ESG 工作的一部分來完善您的負擔得起的藥物組合的東西嗎？所以那裡的任何顏色都會有所幫助。

Thank you, Marietta. So Harry, on margin dynamics and cost savings.

謝謝你，瑪麗埃塔。所以哈利，關於利潤動態和成本節約。

Yes, I think, overall, Vas laid out 3 major elements of our productivity efforts, one being the network transformation and the other 2 being the business services and procurement. So to -- I would say on the business services and procurement, we are starting. So we have some impact, but the majority is still to come. And on the network transformation, we have already kind of the middle. So I would say kind of we have started kind of 25% there and we keep going. All of this is of course included in our midterm -- in our 2019 margin and the midterm aspiration to go to mid-30s for Innovative Medicines. But we have started, but I would say on especially business services and procurement, still major impact to come. And in terms of Gilenya and the midterm aspiration, grow by 22% of IM margins, I mean, we have several variables which either pushes or pulls that drive headwinds or tailwinds on that. But overall, we clearly see very strong sales growth, growth momentum. Of course, we have some generics exposure, as we discussed earlier. And a single variable would not change for that our aspiration to go to the mid-30s. And then the update as we go. This year or in 2018, we did an increase of 100 basis points in Innovative Medicines from 31% to 32%. So I think that's a good starting point for getting to the mid-30s.

是的，我認為，總的來說，Vas 列出了我們生產力工作的 3 個主要元素，一個是網絡轉型，另一個是業務服務和採購。所以 - 我會說關於商業服務和採購，我們正在開始。所以我們產生了一些影響，但大部分還在後頭。而在網絡改造上，我們已經有點中間了。所以我想說我們已經開始了 25%，我們會繼續前進。所有這些當然都包含在我們的中期——我們 2019 年的利潤率和創新藥物進入 30 年代中期的中期願望中。但是我們已經開始了，但我要說的是，尤其是在商業服務和採購方面，仍然會有重大影響。就 Gilenya 和中期願望而言，IM 利潤率增長 22%，我的意思是，我們有幾個變量可以推動或拉動推動逆風或順風。但總體而言，我們清楚地看到非常強勁的銷售增長和增長勢頭。當然，正如我們之前討論的那樣，我們有一些泛型暴露。一個單一的變量不會改變我們對 30 年代中期的渴望。然後我們進行更新。今年或 2018 年，我們將創新藥物的比例從 31% 提高了 100 個基點至 32%。所以我認為這是進入 30 年代中期的一個很好的起點。

Great. Thanks, Harry. In terms of the Sandoz carve-out, really where we focus on is on business services and manufacturing. It's very early days. Our focus -- real focus in these areas right now is preparing for the Alcon spin. That's where we're going to spend most of our energy for the first half of this year. And then we'll turn to Sandoz and try to enable Sandoz to be an autonomous unit. There will be stand-up costs of course associated with some of these areas within Sandoz. We don't mean to imply otherwise, but we don't expect those stand-up costs to change our expectations of margin improvement from the transformation within Sandoz. I think really that's what we were trying to communicate. And then lastly, on the strategy to enter insulin biosimilars, Richard?

偉大的。謝謝，哈利。就 Sandoz 分拆而言，我們真正關注的是商業服務和製造。現在還很早。我們的重點——目前這些領域的真正重點是為愛爾康的分拆做準備。這就是我們今年上半年將花費大部分精力的地方。然後我們將轉向 Sandoz 並嘗試使 Sandoz 成為一個自治單元。當然，Sandoz 內的某些領域會產生站立費用。我們無意暗示其他情況，但我們預計這些站立成本不會改變我們對 Sandoz 內部轉型帶來的利潤率提高的預期。我認為這確實是我們試圖傳達的內容。最後，關於進入胰島素生物仿製藥的戰略，Richard？

Yes. Thanks for the question. So the way we look at it, we think about our portfolio -- about a couple of things. Firstly, what is the opportunity from a business point of view, what does the access need from a medical point of view and then how do we leverage our current infrastructure? And I think the exciting thing about the insulin market is, one, this is a huge market, over $10 billion net sales and growing in the U.S. We're also seeing the pricing of that market continue to go up. So that market has been growing year-on-year. I think one of the things we've thought about in the past is, firstly, are there are going to be disruptive innovation that's going to come along and change the care that's -- the standard of care that's given to these patients? We don't believe that's the case. And one of the other things we think about is that manufacturing is one of the barriers for this. The volumes required to really enter this market and be successful are huge. And I think that's something that, in the past, I think we probably looked and thought that's not where we want to spend our capital. But the great thing is with the partnership that we have with Gan & Lee is they have a manufacturing capability -- first-rate manufacturing capability. They make insulins in China already and so we have an ability to work and developing a portfolio with them, bringing to market cost effectively because we can leverage our commercial infrastructure and we can leverage their manufacturing capacity. Because there's no innovation coming forward, we actually think this is an attractive market. And I think we've seen over the last year or 2 a number of people actually pull out of this market for whatever strategic reasons they've had, but that even makes it even more attractive. So I think this is more -- we think there's an opportunity. We found a way with good partnership to maximize it. So I think this actually is a good growth driver.

是的。謝謝你的問題。所以我們看待它的方式，我們考慮我們的投資組合——關於幾件事。首先，從商業角度來看機會是什麼，從醫療角度來看訪問需要什麼，然後我們如何利用我們當前的基礎設施？我認為胰島素市場令人興奮的事情是，第一，這是一個巨大的市場，淨銷售額超過 100 億美元，並且在美國不斷增長。我們還看到該市場的定價繼續上漲。所以這個市場一直在逐年增長。我認為我們過去考慮過的一件事是，首先，是否會出現顛覆性創新並改變護理——為這些患者提供的護理標準？我們認為情況並非如此。我們考慮的另一件事是製造是實現這一目標的障礙之一。真正進入這個市場並取得成功所需的數量是巨大的。我認為這是過去的事情，我認為我們可能認為這不是我們想要花錢的地方。但我們與甘李的合作夥伴關係的偉大之處在於他們擁有製造能力——一流的製造能力。他們已經在中國生產胰島素，因此我們有能力與他們合作並開發產品組合，以經濟高效的方式將產品推向市場，因為我們可以利用我們的商業基礎設施，也可以利用他們的製造能力。因為沒有創新，我們實際上認為這是一個有吸引力的市場。而且我認為，在過去一兩年中，我們已經看到許多人實際上出於戰略原因退出了這個市場，但這甚至使它更具吸引力。所以我認為這更多 - 我們認為有機會。我們找到了一種與良好合作夥伴關係最大化的方法。所以我認為這實際上是一個很好的增長動力。

Great. Thanks, everyone, for joining today's call. We went quite a bit over time, but we appreciate everybody's questions. We appreciate our investors' commitment to investing in our company, and we look forward to providing you updates in the months to come.

偉大的。謝謝大家參加今天的電話會議。隨著時間的推移，我們進行了相當多的討論，但我們感謝大家提出的問題。我們感謝投資者對投資我們公司的承諾，我們期待在未來幾個月為您提供最新信息。

Thank you.

謝謝。

Thank you very much for joining today's Novartis' conference call.

非常感謝您參加今天的諾華電話會議。