Novartis AG (NVS) 2019 Q3 法說會逐字稿

Good morning, and good afternoon, and welcome to the Novartis Q3 2019 Results Release Conference Call and Live Audio Webcast. (Operator Instructions) And the conference is being recorded. (Operator Instructions) A recording of the conference call, including the Q&A session, will be available on our website shortly after the call ends. (Operator Instructions)

早上好，下午好，歡迎來到諾華 2019 年第三季度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）電話會議的錄音，包括問答環節，將在電話會議結束後不久在我們的網站上提供。（操作員說明）

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

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

Thank you very much, and good morning and good afternoon, everybody. Thank you so much for taking the time to join us for the investor call.

非常感謝，大家早上好，下午好。非常感謝您抽出寶貴時間參加我們的投資者電話會議。

Before we start, I'll just read to you 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.

在我們開始之前，我將向您宣讀安全港聲明。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。

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

然後，我將交給 Vas。

Thank you, Samir, and thanks, everyone, for joining today's conference call. As you saw earlier today, we announced what I think are really excellent results demonstrating the strong operational performance happening at Novartis, our continued progress on our innovation as well as continuing to drive our strategic priorities, which we believe will drive sustainable long-term top and bottom line growth.

謝謝薩米爾，也感謝大家參加今天的電話會議。正如您今天早些時候所看到的，我們宣布了我認為非常出色的結果，展示了諾華公司強勁的運營業績、我們在創新方面的持續進步以及繼續推動我們的戰略重點，我們相信這將推動可持續的長期增長和底線增長。

When you go to slide -- the first slide, Slide 4, just to give a little more color on what you all saw earlier today. We had double-digit top and bottom line growth in the quarter. Sales were up 13%, core operating income up 18% and core margin up 1.4%. Harry will go through these numbers in more detail along with describing in a bit more detail as well our guidance increase where we increased both sales and core operating income guidance for the year.

當您轉到幻燈片時——第一張幻燈片，幻燈片 4，只是為了讓大家今天早些時候看到的內容多一點色彩。我們在本季度實現了兩位數的收入和利潤增長。銷售額增長 13%，核心營業收入增長 18%，核心利潤率增長 1.4%。Harry 將更詳細地介紹這些數字，並更詳細地描述我們的指導增長，我們增加了今年的銷售額和核心營業收入指導。

Equally as important, we had strong innovation performance in the quarter. When you look at it, we're on -- we are on track to potentially have 4 or potentially 5 new molecular entities approved in the United States, which really shows the kind of innovation power we have in the company. Beovu was launched in the U.S., ofatumumab, of course, compelling efficacy in RMS and then a number of other key milestones, many of which we'll go through over the course of this call.

同樣重要的是，我們在本季度的創新表現強勁。當你看它時，我們正在——我們有望在美國批准 4 種或 5 種新的分子實體，這確實顯示了我們公司的創新能力。Beovu 在美國推出，ofatumumab，當然，在 RMS 中具有令人信服的功效，然後是許多其他關鍵里程碑，其中許多我們將在本次電話會議中經歷。

So turning to the next slide. One of the most important trends we want to start highlighting is how our key growth drivers are increasingly contributing to our overall sales performance. When you look at Innovative Medicines sales 9 months to date in 2019, we've grown now to have 28% of our sales coming from our key growth drivers. And many of these key growth drivers have very strong underlying dynamics, as we'll talk about on the next slide.

轉到下一張幻燈片。我們要開始強調的最重要趨勢之一是我們的主要增長動力如何對我們的整體銷售業績做出越來越大的貢獻。當您查看 2019 年迄今為止 9 個月的創新藥物銷售額時，我們現在已經增長到 28% 的銷售額來自我們的主要增長動力。正如我們將在下一張幻燈片中討論的那樣，許多這些關鍵增長驅動因素都具有非常強大的潛在動力。

In addition, our growth contribution is primarily coming from these growth drivers. We do have some, of course, Gx erosion and then some other benefits. But overall, the primary contributor to our growth year-to-date has been these key growth drivers, most of which are recent launches.

此外，我們的增長貢獻主要來自這些增長動力。當然，我們確實有一些 Gx 侵蝕和其他一些好處。但總的來說，我們今年迄今增長的主要貢獻者是這些關鍵的增長動力，其中大部分是最近推出的。

Now if you go to Slide 6, you can see in a bit more detail, we had broad-based strong growth across our growth drivers across the portfolio, whether that was in Pharmaceuticals with Cosentyx, Entresto, Xiidra, Zolgensma in our cell and gene therapies effort and in oncology, where also you see broad-based growth. So I think when you look at it overall, we're firing really on all cylinders as a company in terms of driving our in-line brand and launch brand.

現在，如果你轉到幻燈片 6，你可以更詳細地看到，我們在整個產品組合的增長驅動因素中實現了廣泛的強勁增長，無論是在我們的細胞和基因中使用 Cosentyx、Entresto、Xiidra、Zolgensma 的藥物在治療和腫瘤學方面，您也可以看到基礎廣泛的增長。所以我認為，當你從整體上看時，我們作為一家公司在推動我們的在線品牌和發布品牌方面確實在全力以赴。

Now if you go to the next slide, Slide 7. Diving in deeper into the individual products, let's start with Cosentyx. And in Cosentyx, we once again had a very strong quarter with 27% overall sales growth, driven by both strong ex U.S. and U.S. performance.

現在，如果您轉到下一張幻燈片，即幻燈片 7。深入了解各個產品，讓我們從 Cosentyx 開始。在 Cosentyx 中，我們再次有一個非常強勁的季度，整體銷售額增長了 27%，這得益於強勁的美國和美國業績。

Now I'll first start talking a bit about dermatology. There, we see the market growing at 17% from a TRx standpoint, and Cosentyx continuing to grow ahead of the market at 32% despite intensifying competition. So we believe we're well placed. We also believe we will be well placed next year to maintain our first-line positioning, and we'll be happy to answer more questions about that in the Q&A.

現在我將首先開始談論皮膚病學。在那裡，從 TRx 的角度來看，我們看到市場增長了 17%，儘管競爭加劇，Cosentyx 仍以 32% 的速度繼續領先於市場。所以我們相信我們的位置很好。我們也相信明年我們將有能力保持我們的一線定位，我們很樂意在問答中回答更多相關問題。

And then when you look in rheumatology, we also are continuing to have a strong growth based on our strong underlying data where we grow 36% versus a market that's growing at 15%. We had some positive news as well with an additional CHMP opinion on the higher dose as well as the PREVENT trial meeting primary endpoints at 16 and 52 weeks.

然後當你看風濕病學時，我們也將繼續保持強勁增長，基於我們強大的基礎數據，我們增長了 36%，而市場增長了 15%。我們也有一些積極的消息，以及 CHMP 對更高劑量的額外意見以及 PREVENT 試驗在 16 周和 52 週時達到主要終點。

To go into a little bit more detail on the next slide on where Cosentyx is building further positions in the market, our non-radiographic axial SpA data clearly shows the potential of Cosentyx to move into a broader range of patients with ankylosing spondylitis. When you look at the left-hand side of the chart, you can see there are 3.2 million patients with psoriatic arthritis, 1.7 million patients with ankylosing spondylitis and then an equal number of patients with non-radiographic axial spondyloarthritis.

為了在下一張幻燈片中更詳細地介紹 Cosentyx 在市場上建立更多地位的位置，我們的非放射線軸向 SpA 數據清楚地顯示了 Cosentyx 進入更廣泛的強直性脊柱炎患者的潛力。當您查看圖表的左側時，您可以看到有 320 萬銀屑病關節炎患者、170 萬強直性脊柱炎患者和同樣數量的非放射學中軸型脊柱關節炎患者。

When you look at the biologics penetration in this kind of early SpA group, there's biologics penetration of only 4% to 8%. So this is an exciting opportunity for us now to take forward around the world.

當您查看此類早期 SpA 組的生物製劑滲透率時，生物製劑滲透率僅為 4% 至 8%。因此，這對我們來說是一個激動人心的機會，可以在世界範圍內取得進展。

We're also well positioned beyond just the current rheumatology indications when you look at some of the data readouts we have, but importantly, additional clinical trials we have in Hidradenitis Suppurativa pediatric indications as well as additional new studies starting in rheumatology, including giant cell arteritis. We feel very confident in Cosentyx' longer-term trajectory and we look forward at R&D Day to give you more color on some of those additional indication programs.

當您查看我們擁有的一些數據讀數時，我們也處於超越當前風濕病適應症的有利位置，但重要的是，我們在化膿性汗腺炎兒科適應症方面進行的其他臨床試驗以及風濕病學開始的其他新研究，包括鉅細胞動脈炎。我們對 Cosentyx 的長期發展軌跡非常有信心，我們期待在研發日為您提供一些額外適應症項目的更多信息。

Now moving to the next slide with Entresto. With Entresto, we continue to see strong underlying dynamics. Entresto revenues were up 61%, with growth -- strong growth both in the ex U.S. and U.S. When you look at weekly TRxs, we are up 51% Q3 2018 to Q3 2019. And as you can see from the slope of the line, we just have this continued solid steady uptake in TRx in the U.S. and we see a similar trend in other key markets around the world. Now both PROVE-HF and EVALUATE-HF provided additional mechanistic support for Entresto, and we see that increasingly influencing guideline bodies around the world. FDA also approved a pediatric indication for Entresto in Q4.

現在轉到下一張 Entresto 幻燈片。通過 Entresto，我們繼續看到強大的潛在動力。Entresto 的收入增長了 61%，增長了——在美國以外和美國的強勁增長。當你查看每週的 TRxs 時，我們從 2018 年第三季度到 2019 年第三季度增長了 51%。正如您從直線的斜率中看到的那樣，我們在美國的 TRx 中持續穩步增長，我們在全球其他主要市場也看到了類似的趨勢。現在 PROVE-HF 和 EVALUATE-HF 都為 Entresto 提供了額外的機制支持，我們看到這對全球指南機構的影響越來越大。FDA 還在第四季度批准了 Entresto 的兒科適應症。

Then moving to the next slide. When you look at the PARAGON-HF study, which we read out in Q3, and I think many of you already know these results as described at ESC, the preserved ejection fraction heart failure population is a population that currently is completely unserved. And these patients are looking for some treatment option. We narrowly missed the primary endpoint on the overall population, but we had important subgroups, including the subgroup of patients with an ejection fraction up to 57% as well as female patients in the study with significant benefits.

然後轉到下一張幻燈片。當您查看我們在第 3 季度宣讀的 PARAGON-HF 研究時，我想你們中的許多人已經知道 ESC 上描述的這些結果，射血分數保留的心力衰竭人群是目前完全沒有得到服務的人群。這些患者正在尋找一些治療方案。我們勉強錯過了總體人群的主要終點，但我們有重要的亞組，包括射血分數高達 57% 的患者亞組以及研究中具有顯著益處的女性患者。

So after discussions with the U.S. FDA, we now plan to move forward with a regulatory submission for inclusion of data into the label in Q4 2019. We're continuing to engage in discussions with Europe, EU and other regulators to discuss how best to take forward this data. We are determined to try to find a way to reflect the benefits of Entresto in a broader patient population in an appropriate way.

因此，在與美國 FDA 討論後，我們現在計劃在 2019 年第四季度提交一份監管文件，將數據納入標籤。我們將繼續與歐洲、歐盟和其他監管機構進行討論，討論如何最好地推進這些數據。我們決心嘗試找到一種方法，以適當的方式在更廣泛的患者群體中反映 Entresto 的益處。

Now if you go to Slide 11. Zolgensma, off to a strong start, as you saw year-to-date with sales of $175 million since launch. A few comments on access. I'm very proud of our access efforts within our team in the U.S. They've done an outstanding job. Getting now access is 90% of commercial patients and 30% Medicaid patients with a policy in place. Importantly, we are now still seeing 99% final approval rates for patients that are on label after we go through the appropriate appeals processes. We are seeing solid demand in a broad base of institutions, over 50 treating institutions now in the U.S., including many leading academic centers of excellence have prescribed now Zolgensma. And when you look at the patient profile, we're seeing patients across SMA types, the incident and prevalent populations as well as 50% patients coming from switches from the previous -- currently licensed product, nusinersen.

現在，如果你轉到幻燈片 11。Zolgensma 開局良好，正如你所看到的那樣，自推出以來今年迄今的銷售額為 1.75 億美元。關於訪問的一些評論。我為我們在美國的團隊所做的訪問工作感到非常自豪。他們做得非常出色。現在獲得訪問權的是 90% 的商業患者和 30% 有政策的醫療補助患者。重要的是，在我們通過適當的上訴程序後，我們現在仍然看到標籤上患者的最終批准率為 99%。我們在廣泛的機構基礎上看到了強勁的需求，現在美國有 50 多家治療機構，包括許多領先的卓越學術中心，現在已經規定了 Zolgensma。當你查看患者資料時，我們看到 SMA 類型的患者、事件和流行人群以及 50% 的患者來自以前的開關——目前獲得許可的產品 nusinersen。

So if you go to Slide 12. Looking forward for Zolgensma, I think a general comment I'd say is you can expect -- given that in Q3 we worked up through some of the pent-up demand for the product, much of which we had also addressed through a Managed Access Program, but there was some pent-up demand still we were working through in Q3. We expect Q4 to be broadly in line with Q3 for Zolgensma. But then moving forward, we see opportunities both in the U.S. and outside the United States.

所以如果你轉到幻燈片 12。期待 Zolgensma，我想我想說的一般性評論是你可以期待的——鑑於在第三季度我們解決了對該產品的一些被壓抑的需求，其中大部分我們也通過託管訪問解決了計劃，但我們在第三季度仍有一些被壓抑的需求。我們預計 Zolgensma 的第四季度與第三季度大致一致。但展望未來，我們看到了美國和美國以外的機會。

First, in the U.S. we expect that newborn screening climbs from 30% of newborns to 70% of newborns or higher by the end of 2020. This will be an important additional growth driver for Zolgensma. We also -- and we know that 2/3 of incident patients treated in states with newborn screening are getting Zolgensma. So I think this is an important trend for us. We also expect Medicaid policies to increasingly come into place over the coming 12 months, including in Florida, New Jersey and Michigan. And many of you saw our interim STRONG data, which really showed, I think, the strong profile of Zolgensma in SMA Type 2 patients with impressive scores on the HFMSE scoring for patients 2 to 5 years of age.

首先，在美國，我們預計到 2020 年底，新生兒篩查率將從 30% 上升到 70% 或更高。這將成為 Zolgensma 重要的額外增長動力。我們也——而且我們知道，在接受新生兒篩查的州接受治療的事件患者中有 2/3 正在接受 Zolgensma。所以我認為這對我們來說是一個重要的趨勢。我們還預計，在未來 12 個月內，醫療補助政策將越來越多地實施，包括在佛羅里達州、新澤西州和密歇根州。你們中的許多人都看到了我們的中期 STRONG 數據，我認為，這確實表明了 Zolgensma 在 2 至 5 歲患者的 HFMSE 評分中取得令人印象深刻的分數的 SMA 2 型患者的強大形象。

Right now, from a regulatory standpoint, we're awaiting FDA feedback on the IT filing approach. We have provided FDA with the data set that we recently presented and are discussions with the FDA on the appropriate approach to filing. For Zolgensma in the current IV indication, we expect CHMP opinion in Q1 2020. I know there are questions surrounding that. The primary reason for that were an extensive set of questions with respect to the manufacturing in CMC. We've now submitted those responses, but we need to continue to work through these responses with EMA to get to the final positive opinion.

現在，從監管的角度來看，我們正在等待 FDA 對 IT 備案方法的反饋。我們已向 FDA 提供了我們最近提交的數據集，並正在與 FDA 討論適當的備案方法。對於目前 IV 適應症的 Zolgensma，我們預計 CHMP 將在 2020 年第一季度發表意見。我知道圍繞這一點存在疑問。主要原因是關於 CMC 製造的一系列廣泛問題。我們現在已經提交了這些回复，但我們需要繼續與 EMA 一起處理這些回复，以得出最終的肯定意見。

And then in Japan, we expect a decision in first half 2020. We, importantly, have early access programs now in place in France, Portugal and Germany. So overall, I think Zolgensma, well on track to reach our longer-term aspiration.

然後在日本，我們預計將在 2020 年上半年做出決定。重要的是，我們現在在法國、葡萄牙和德國實施了搶先體驗計劃。因此，總的來說，我認為 Zolgensma 有望實現我們的長期目標。

If you move to Slide 13, Beovu is off to a strong start in the U.S. When you look at the U.S. launch at AAO with a highly competitive label, we're very excited about this medicine. We see it as a medicine that provides benefits both with the possibility for patients to have fewer intravitreal injection but also important data with respect to visual and anatomical measures of the disease. You have longer treatment intervals achievable without compromising efficacy. That's a key differentiator for this medicine. We have supportive label language on visual and anatomical measures, which will enable us to discuss the important data we have both with respect to retinal fluid and central retinal subfield thickness. And we have an overall safety profile in line with comparator products on the market.

如果你轉到幻燈片 13，Beovu 在美國有一個良好的開端。當你看到美國在 AAO 上推出具有高度競爭力的標籤時，我們對這種藥物感到非常興奮。我們將其視為一種藥物，它既可以為患者提供更少的玻璃體內註射的可能性，又可以提供與疾病的視覺和解剖測量有關的重要數據。您可以在不影響療效的情況下實現更長的治療間隔。這是該藥的一個關鍵區別。我們有關於視覺和解剖測量的支持性標籤語言，這將使我們能夠討論我們擁有的關於視網膜液體和中央視網膜子區域厚度的重要數據。我們的整體安全性與市場上的比較產品一致。

So taken together, we think this is a very compelling case. We can say that at least the early signs are very positive on how the launch is already going. So we look forward to keeping you up-to-date on how the Beovu U.S. launch progresses. Now if you go to the next slide, we also have a broad comprehensive clinical trial program ongoing to look both at potential new indications as well as to better profile Beovu in the core AMD indication.

綜上所述，我們認為這是一個非常有說服力的案例。我們可以說，至少早期的跡象表明發射已經進行得非常積極。因此，我們期待讓您了解 Beovu 美國發布的最新進展。現在，如果您轉到下一張幻燈片，我們還有一個廣泛的綜合臨床試驗計劃正在進行中，以研究潛在的新適應症以及更好地描述 Beovu 在核心 AMD 適應症中的表現。

A few things to highlight here -- and of course, we're happy to provide more details in the R&D Day on this overall program -- but when you look at the TALON study, it's a head-to-head superiority study of Beovu versus aflibercept evaluating treatment interval duration in an identical treat-to-control regimen, I think this is a study which shows our confidence in the overall profile of the medicine.

這裡有幾件事要強調——當然，我們很高興在研發日提供關於這個整體計劃的更多細節——但當你看一下 TALON 研究時，它是 Beovu 的頭對頭優勢研究與阿柏西普在相同的治療-對照方案中評估治療間隔持續時間相比，我認為這是一項表明我們對藥物整體概況充滿信心的研究。

We have the MERLIN study, which is a head-to-head noninferiority study to cover the q4week population, which we believe will be a small portion of patients that will need q4 dosing, but nonetheless one patient population we want to address.

我們有 MERLIN 研究，這是一項針對 q4week 人群的頭對頭非劣效性研究，我們認為這將是一小部分需要 q4 給藥的患者，但仍然是我們想要解決的一個患者群體。

We also have a head-to-head superiority study ongoing in PCV, which is another opportunity for us to continue to differentiate the medicine. I think the key message here is we have confidence in Beovu, confidence in the potential of this medicine to be a significant advance for patients with these diseases.

我們還在 PCV 中進行了一項頭對頭優勢研究，這是我們繼續區分藥物的另一個機會。我認為這裡的關鍵信息是我們對 Beovu 有信心，相信這種藥物有可能成為這些疾病患者的重大進步。

Now if you move to Slide 15. Ofatumumab also read out in the quarter with, I think, really extraordinary data. When you look at it, it now can be a high-efficacy disease-modifying therapy. But our goal will be to position it being able to be used early and broadly. We think of this as not a medicine we're focused on competing within the B-cell space. We want patients with RMS to have access to B-cell therapy as early as possible in their disease progression.

現在，如果你轉到幻燈片 15。Ofatumumab 在本季度還讀出了我認為非常出色的數據。當你看它的時候，它現在可以成為一種高效的疾病緩解療法。但我們的目標是將其定位為能夠儘早廣泛使用。我們認為這不是我們專注於在 B 細胞空間內競爭的藥物。我們希望 RMS 患者在疾病進展期間儘早獲得 B 細胞治療。

When you looked at the data, you saw strong efficacy results versus teriflunomide across a range of different endpoints. I think all of you have seen that data. Also a highly competitive overall profile, high efficacy, favorable safety profile, continuous -- convenient subcutaneous injection with an autoinjector and no need for an infusion center. And our plan is to initiate worldwide regulatory submissions starting in Q4 2019.

當您查看數據時，您會發現在一系列不同的終點上與特立氟胺相比具有很強的療效。我想你們都看過那個數據。還有一個極具競爭力的整體概況、高效、良好的安全概況、連續——方便的皮下注射和自動注射器，不需要輸液中心。我們的計劃是從 2019 年第四季度開始在全球範圍內提交監管文件。

One thing I wanted to clarify that may have been misunderstood from our press release, our U.S. filing is a filing. It's not a rolling submission. We only meant to imply that we will be rolling out our submissions around the world over the course of the coming months, but our U.S. filing is a straight filing, complete filing that will happen in Q4 of this year.

我想澄清的一件事可能被我們的新聞稿誤解了，我們的美國申請是一份申請。這不是滾動提交。我們只是想暗示我們將在未來幾個月內在全球範圍內推出我們的提交，但我們的美國提交是直接提交，將在今年第四季度完成提交。

So moving to Slide 16. Now look -- turning to Mayzent. So with Mayzent, I think, as many of you have seen, very strong market feedback, very strong interest from physicians and patients. It has a unique label with unique data, the only medicine ever to be studied successfully in secondary progressive, active secondary progressive MS, with very strong data that we continue to roll out, including recent data on cognitive processing speed as well as a 4-year delay to the need to use a wheelchair. We are seeing strong interest in the medicine, 90% willingness to prescribe, over 2,600 request forms now and 150 million lives with preferred and unrestricted access.

所以轉到幻燈片 16。現在看——轉向 Mayzent。所以對於 Mayzent，我認為，正如你們中的許多人所看到的，非常強烈的市場反饋，以及來自醫生和患者的非常強烈的興趣。它有一個獨特的標籤和獨特的數據，是唯一一種在二次進展、活躍的二次進展 MS 中成功研究的藥物，我們將繼續推出非常強大的數據，包括關於認知處理速度的最新數據以及 4-一年延遲到需要使用輪椅。我們看到人們對這種藥物產生了濃厚的興趣，90% 的人願意開處方，現在有超過 2,600 份申請表，1.5 億人的生命可以優先和不受限制地使用。

Our key goal now is to enable a more rapid onboarding of these patients. We're seeing right now about a 90-day lag between initial interest in the medicine and actually getting patients fully onboard with paid RXs. We expect to work hard to shorten that time line as well as work through the backlog of patients, drive an urgency to treat, simplify the onboarding. And we hope then to be able to demonstrate further sales progress in the coming quarter. But overall, we think we're in a solid place with respect to how the medicine is being perceived with the foundations now put into place. We expect CHMP positive opinion in late Q4 2019.

我們現在的主要目標是使這些患者能夠更快地入職。我們現在看到，從最初對該藥物產生興趣到實際讓患者完全接受付費 RX 之間存在大約 90 天的滯後。我們希望努力縮短時間，並解決患者積壓的問題，推動治療的緊迫性，簡化入職流程。我們希望能夠在下一季度展示進一步的銷售進展。但總的來說，我們認為在現在已經建立的基礎上，我們在如何看待藥物方面處於穩固的地位。我們預計 CHMP 將在 2019 年第四季度末發表積極意見。

Moving to Slide 17, now fevipiprant. Fevipiprant, today, we announced the results of the ZEAL 1 and 2 study, but it's important to note where ZEAL 1 and 2 fits into the overall program. Our core goal with fevipiprant was to study the medicine in severe asthma with a focus on high eosinophil severe asthma as other biologics have studied. That is the core group of the LUSTER 1 and 2 programs, with a further potential to look at patients who are low eosinophils in that study. That is the core of the overall fevipiprant study -- program.

轉到幻燈片 17，現在是 fevipiprant。Fevipiprant，今天，我們公佈了 ZEAL 1 和 2 研究的結果，但重要的是要注意 ZEAL 1 和 2 在整個計劃中的位置。我們與 fevipiprant 的核心目標是研究嚴重哮喘的藥物，重點是高嗜酸性粒細胞嚴重哮喘，正如其他生物製劑所研究的那樣。這是 LUSTER 1 和 2 計劃的核心組，在該研究中有進一步觀察低嗜酸性粒細胞患者的潛力。這是整個 fevipiprant 研究項目的核心。

We also were asked to study, as is often the case with these programs, to study the medicine in less-severe patients using an FEV1 endpoint, and that was the ZEAL 1 and 2 programs in so-called GINA 3/4 patients, the kind of moderate severity asthma patient. And there, we saw no significant improvements in FEV1 on top of the standard ICS/LABA regimen, but we saw a very clean safety profile. It's important to note we only took the 150-milligram dose into this population and we did not stratify for eosinophils as well. So right now, we are continuing to work through the completion of the LUSTER program and look forward to reading out that program in full in Q1 2020.

我們還被要求研究，就像這些項目經常發生的情況一樣，使用 FEV1 終點研究不太嚴重的患者的藥物，這就是所謂的 GINA 3/4 患者的 ZEAL 1 和 2 項目，一種中度嚴重的哮喘患者。在標準 ICS/LABA 方案之上，我們沒有看到 FEV1 有顯著改善，但我們看到了非常乾淨的安全性。重要的是要注意我們只對這個人群服用了 150 毫克的劑量，我們也沒有對嗜酸性粒細胞進行分層。所以現在，我們正在繼續完成 LUSTER 計劃，並期待在 2020 年第一季度全面宣讀該計劃。

Now moving to the next slide. Now switching gears to oncology. While oncology had a broad-based outstanding performance with double-digit sales growth, I wanted to highlight the outstanding performance we had in terms of one of our launches, Piqray. So Piqray was launched as the first and only therapy for advanced breast care -- breast cancer patients with PIK3CA mutation. When you look at the sales growth here, you can see a really strong uptake. 40% of patients with hormone-receptor positive/HER2-negative advanced breast cancer have a PIK3CA mutation. So really, our goal here was to ensure broad-based uptake of testing. And I think our teams in the U.S. have done an outstanding job enabling that testing to be broadly available. We now expect CHMP positive opinion in the first half of -- CHMP opinion in the first half of 2020. And our focus is to take Piqray into additional indications, including programs in HER2-positive breast cancer, triple-negative breast cancer, head and neck cancers and ovarian cancers. So you'll see us continuing to work to expand the utilization of Piqray. And we believe this medicine can be a blockbuster over time.

現在轉到下一張幻燈片。現在轉向腫瘤學。雖然腫瘤學有著廣泛的傑出表現和兩位數的銷售額增長，但我想強調我們在我們推出的產品之一 Piqray 方面的出色表現。因此 Piqray 作為第一個也是唯一一個針對高級乳腺護理的療法——具有 PIK3CA 突變的乳腺癌患者推出。當您查看此處的銷售增長時，您會看到非常強勁的增長。40% 的激素受體陽性/HER2 陰性晚期乳腺癌患者有 PIK3CA 突變。因此，實際上，我們的目標是確保廣泛接受測試。而且我認為我們在美國的團隊做得非常出色，使該測試能夠廣泛使用。我們現在預計 CHMP 將在 2020 年上半年發表積極意見 - CHMP 意見。我們的重點是將 Piqray 用於其他適應症，包括 HER2 陽性乳腺癌、三陰性乳腺癌、頭頸癌和卵巢癌的項目。所以你會看到我們繼續努力擴大 Piqray 的使用範圍。我們相信隨著時間的推移，這種藥物會成為重磅炸彈。

Moving to Slide 19. We also released additional data on Kisqali, demonstrating the overall survival benefit of this medicine, as the only CDK 4/6 inhibitor to demonstrate overall survival in 2 Phase III trials. One important element to remember about Kisqali is we believe that it's unique in its profile and its ability to agonize the CDK 4 part of this pathway. And with that unique profile, we think that really enables us to have a mechanistic differentiation for Kisqali. Now our goal right now is to continue to educate the physician community about the MONALEESA-3 and MONALEESA-7 data, particularly the 28% and 29% reductions in the risk of death. And we'll look forward to further differentiating Kisqali with additional readouts, including the MONALEESA-2 overall survival data, which we'll read out next year.

轉到幻燈片 19。我們還發布了關於 Kisqali 的額外數據，證明了該藥物的總體生存益處，作為唯一在 2 項 III 期試驗中證明總體生存的 CDK 4/6 抑製劑。關於 Kisqali 需要記住的一個重要因素是，我們相信它的獨特之處在於它的獨特之處以及它能夠刺激該途徑的 CDK 4 部分。憑藉這種獨特的形象，我們認為這確實使我們能夠對 Kisqali 進行機械差異化。現在，我們現在的目標是繼續讓醫生社區了解 MONALEESA-3 和 MONALEESA-7 數據，尤其是死亡風險降低 28% 和 29% 的數據。我們期待通過其他讀數進一步區分 Kisqali，包括我們將在明年讀出的 MONALEESA-2 總體生存數據。

Now moving to Slide 20. If you look at our overall 2019 expected milestones, I think we had a great innovation performance year-to-date, and we hope to carry that forward with a strong finish to the year. You can see that we've reached nearly all of our milestones. A few milestones were pushed into the first part of next year. But overall, I think a very strong performance.

現在轉到幻燈片 20。如果你看一下我們 2019 年的總體預期里程碑，我認為我們今年迄今為止的創新表現非常出色，我們希望在今年取得出色的成績。你可以看到我們已經達到了幾乎所有的里程碑。一些里程碑被推遲到明年上半年。但總的來說，我認為表現非常強勁。

When you go to Slide 21, I wanted to just highlight a few of the catalysts. We expect a number of key approvals next year. Importantly, ofatumumab and Cosentyx in non-radiographic axial SpA but also SEG101 in sickle cell disease. A range of key submissions. We've already talked about AveXis and fevipiprant, but we also will have the readout and hopeful submission of the data are positive of Lu-PSMA, one of our radioligand therapies for prostate cancer as well as the submission of our triplet combo with PDR001 in Mekinist + Tafinlar. And lastly, a range of key readouts, we're excited to tell you more about our -- depth of our portfolio in our R&D Day in early December. But a few to highlight, ABL001 in CML, which we also now are planning to use in other lines of therapy. We also will have readouts in Beovu and DME. A range of Phase II readouts: I'll note LNP023, which is our Factor B inhibitor, we'll have data presented at ASH and I think can eventually be a cornerstone therapy for PNH and renal diseases. So a range of things going on, and we'll provide more depth on those milestones in early December.

當你轉到幻燈片 21 時，我只想強調一些催化劑。我們預計明年將獲得多項重要批准。重要的是，ofatumumab 和 Cosentyx 用於非放射學中軸 SpA，還有 SEG101 用於鐮狀細胞病。一系列關鍵提交。我們已經討論過 AveXis 和 fevipiprant，但我們也將獲得 Lu-PSMA 的讀數和希望提交的數據，Lu-PSMA 是我們用於前列腺癌的放射配體療法之一，以及我們與 PDR001 的三重組合的提交曲美替尼+ Tafinlar。最後，一系列關鍵讀數，我們很高興在 12 月初的研發日向您詳細介紹我們的產品組合深度。但有幾點需要強調，CML 中的 ABL001，我們現在也計劃將其用於其他治療線。我們還將在 Beovu 和 DME 中進行讀數。一系列 II 期讀數：我會注意到 LNP023，它是我們的 B 因子抑製劑，我們將在 ASH 上提供數據，我認為最終可以成為 PNH 和腎臟疾病的基石療法。所以發生了一系列事情，我們將在 12 月初提供有關這些里程碑的更多深度。

So with that, I'll hand it over to Harry.

因此，我將把它交給哈利。

Thank you, Vas. Good morning, good afternoon, everyone. As always, my comments refer to the results of the continuing operations and growth rates in constant currencies, unless I note otherwise.

謝謝你，瓦斯。大家早上好，下午好。一如既往，除非另有說明，否則我的評論指的是持續經營的結果和以固定貨幣計算的增長率。

So on Slide 23, you see the summary of our quarter 3 and first 9 months continuing operations performance. As Vas said, our quarter 3 performance was excellent with double-digit sales growth driving core operating income and strong cash flow of $4 billion. Sales grew 13%, mainly driven by continued momentum of key growth drivers, as Vas laid out. We also benefited from the first full quarter of the strong launch of Zolgensma and Piqray as well as the acquisition of Xiidra. Core operating income grew 18%, mainly driven by sales and also productivity program impacts. You see a similar pattern on year-to-date results. Year-to-date sales growth of 9% drove core operating income growth of 18% and resulting in free cash flow of $9.4 billion in the first 9 months.

因此，在幻燈片 23 上，您可以看到我們第 3 季度和前 9 個月的持續運營績效摘要。正如 Vas 所說，我們第三季度的業績非常出色，兩位數的銷售增長推動了核心營業收入和 40 億美元的強勁現金流。正如瓦斯所說，銷售額增長了 13%，主要是受到關鍵增長動力的持續推動。我們還受益於 Zolgensma 和 Piqray 的強勁推出以及對 Xiidra 的收購的第一個完整季度。核心營業收入增長 18%，主要受銷售和生產力計劃影響的推動。您會在年初至今的結果中看到類似的模式。年初至今 9% 的銷售額增長推動了 18% 的核心營業收入增長，並在前 9 個月產生了 94 億美元的自由現金流。

On Slide 24, we have laid out the first 9 months and quarter 3 core margin by division. Continuing operations margin improved by 1.4 percentage points in the quarter and 2.4 percentage points year-to-date. In Innovative Medicines, strong quarter 3 sales growth of 15% enabled core margin improvement to 34% of sales. Sandoz had a particularly strong quarter with 5% sales growth and 18% core operating income growth, resulting in a core margin of almost 25%. The growth in Sandoz was mainly driven by Biopharmaceuticals growing 27% as well as productivity from the ongoing transformation programs falling through to the bottom line. Additionally, quarter 3 at Sandoz was hedged by, first, 3 first-to-file retail launches in the U.S. and a favorable onetime Medicaid revenue deduction adjustment in the quarter. Overall, year-to-date, you see very strong margin expansions in both divisions, with Sandoz margin of 22% almost and Innovative Medicines margin of 34%.

在幻燈片 24 上，我們按部門列出了前 9 個月和第 3 季度的核心利潤率。本季度持續經營利潤率提高了 1.4 個百分點，年初至今提高了 2.4 個百分點。在創新藥物方面，第三季度銷售額強勁增長 15%，核心利潤率提高至銷售額的 34%。山德士的季度表現尤為強勁，銷售額增長 5%，核心營業收入增長 18%，核心利潤率接近 25%。Sandoz 的增長主要受生物製藥業務增長 27% 以及正在進行的轉型計劃的生產力下降所推動。此外，Sandoz 第 3 季度受到美國 3 個首次提交的零售發布和本季度有利的一次性醫療補助收入扣除調整的對沖。總體而言，年初至今，兩個部門的利潤率都出現了非常強勁的增長，山德士的利潤率幾乎達到 22%，創新藥物的利潤率達到 34%。

On the next slide, Slide 25, just to the guidance. So in light of our really strong performance, we are revising upwards our 2019 full year guidance once more. This is clearly driven by the very good performance of our growth drivers and launches. In addition, we saw less generic impacts on our onco mature products than expected in quarter 3, which we discussed as a scenario at the quarter 2 call.

在下一張幻燈片 25 號幻燈片中，只是為了提供指導。因此，鑑於我們非常強勁的表現，我們再次上調了 2019 年的全年指引。這顯然是由我們的增長動力和發布的出色表現推動的。此外，我們在第 3 季度看到對我們成熟產品的一般影響低於預期，我們在第 2 季度電話會議上將其作為一種情況進行了討論。

So for the new focused medicines company, net sales are revised upwards, expected to grow high single digits; and core operating income for the company revised upwards, expected to grow mid- to high teens. From a divisional perspective, we revised Innovative Medicines' sales guidance upwards to grow high single to low double-digit and Sandoz sales guidance is revised upwards to grow low single-digit.

因此，對於新專注的醫藥公司，淨銷售額被向上修正，預計將增長高個位數；公司的核心營業收入向上修正，預計將增長中高位。從部門的角度來看，我們將 Innovative Medicines 的銷售指引上調至高個位數增長至低兩位數，並將 Sandoz 銷售指引上調至低個位數增長。

On Slide 26, I want to walk you through some of the dynamics for the fourth quarter versus the 9 months. Now we are having a very strong 2019 with core operating income growth of 18% year-to-date. As you can see, this is mainly driven by excellent sales momentum of our growth drivers and launches and also the productivity programs we have put in place. But we had also a very moderate generic impact on some of our older Innovative Medicines brands and upside on valsartan from competitor supply shortages. So as we move into quarter 4, we continue to expect our growth drivers and launches to be very successful. We also expect continued benefits from our ongoing productivity programs. However, we also plan to further increase investments in launches and pre-launches, such as Beovu, Mayzent, Piqray, Xiidra and ofatumumab. As of quarter 3, we do lap the valsartan upside in the base and valsartan generics are starting to return to several markets.

在幻燈片 26 上，我想向您介紹第四季度與前 9 個月的一些動態。現在我們有一個非常強勁的 2019 年，核心營業收入今年迄今增長了 18%。正如您所看到的，這主要是由於我們的增長動力和發布的出色銷售勢頭以及我們已經實施的生產力計劃。但我們也對我們的一些較老的創新藥物品牌產生了非常溫和的仿製藥影響，並且競爭對手供應短缺對纈沙坦產生了上行空間。因此，當我們進入第 4 季度時，我們繼續期望我們的增長動力和發布會非常成功。我們還期望從我們正在進行的生產力計劃中持續受益。然而，我們還計劃進一步增加對上市和預上市的投資，例如 Beovu 、 Mayzent 、 Piqray 、 Xiidra 和 ofatumumab 。截至第 3 季度，我們確實將纈沙坦的優勢推向了基數，而纈沙坦仿製藥開始重返多個市場。

In addition, we expect increased generic competition on Afinitor, Exjade, Jadenu and some mature ophtha brands. However, as always in these cases, we do not know exactly when the generics will enter the market. So if generic entries would come again later or would continue to have minimal impact on our results in quarter 4, we would expect to be at the higher end of the full year guidance. As you know, the above-mentioned mature onco and mature ophtha generic entries are a matter of time and you need to consider that also in your modeling for 2020.

此外，我們預計 Afinitor、Exjade、Jadenu 和一些成熟的眼科品牌的仿製藥競爭將會加劇。然而，在這些情況下，我們並不確切知道仿製藥何時會進入市場。因此，如果通用條目稍後再次出現或對我們在第 4 季度的業績影響最小，我們預計將處於全年指導的較高端。如您所知，上述成熟的 onco 和成熟的 optha 仿製藥條目是時間問題，您也需要在 2020 年的建模中考慮到這一點。

On Slide 27, quickly, let's look at how the currencies would impact our results if mid-October rates would prevail for quarter 4 and for 2020. So you see the effect of the strength -- mainly strengthening dollar to diminish over time in quarter 4 already, but the full year 2019 would be a negative 3% on sales and a negative 5% FX impact on core operating income. In 2020, the currency impact would diminish down to a minus 1% for both sales and core operating income. And as you know, currencies fluctuate a lot. We update this on our website every month, so you have hopefully a very transparent picture on currency impacts on our results on a monthly basis.

在幻燈片 27 上，讓我們快速看看如果 10 月中旬的利率在第 4 季度和 2020 年占主導地位，貨幣將如何影響我們的結果。所以你看到了強勢的影響——主要是美元走強，在第四季度已經隨著時間的推移而減少，但 2019 年全年的銷售額將下降 3%，外匯對核心營業收入的影響將下降 5%。到 2020 年，貨幣對銷售額和核心營業收入的影響將降至負 1%。如您所知，貨幣波動很大。我們每個月都會在我們的網站上更新此信息，因此您希望每個月都能非常透明地了解貨幣對我們結果的影響。

And with that, I hand back to Vas.

就這樣，我交還給 Vas。

Thank you, Harry. So just in summary, when you look at the last slide, we continue to see tremendous momentum overall in the company; whether you look at the sales and operating

謝謝你，哈利。因此，總而言之，當您查看最後一張幻燈片時，我們繼續看到公司整體的巨大發展勢頭；你是否看銷售和運營

(technical difficulty)

（技術難度）

very good about where we are. And I think we look forward to taking your questions.

非常了解我們的位置。我想我們期待著回答您的問題。

So with that, I will hand it back to Samir.

因此，我將把它交還給薩米爾。

Operator, we'll be open for Q&A. (Operator Instructions)

接線員，我們將開放問答。（操作員說明）

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

（操作員說明）我們的第一個問題來自美國銀行的 Graham Parry。

So firstly, on Zolgensma, you talked through some of the moving parts and the potential drivers into next year, but I was wondering if you could express any level of comfort with the consensus number of $1.2 billion at the moment, which would seem to assume either very high penetration into the incident patient population or quite a lot of prevalent patients being accessed through the course of the year. So is there enough prevalent penetration left after your bolus to get you to that number?

所以首先，在 Zolgensma 上，你談到了明年的一些活動部分和潛在驅動因素，但我想知道你是否可以對目前 12 億美元的共識數字表示任何程度的安慰，這似乎假設要么非常高地滲透到事件患者群體中，要么在一年中接觸到相當多的流行患者。那麼在你的推注後是否有足夠的普遍滲透率讓你達到那個數字？

And then secondly on Gilenya, it looks like you've settled that with Mylan looking at the court dockets and the stay there. Could you give us any kind of feel for what sort of time frame that would be coming into the market and whether you would expect to be seeking similar settlements with the other generic filers given the rather positive comments in the preliminary injunction from the judge?

其次是關於 Gilenya，看起來你已經和 Mylan 一起解決了這個問題，看著法庭的案卷並留在那裡。考慮到法官在初步禁令中的相當積極的評論，您能否讓我們了解進入市場的時間框架以及您是否希望與其他仿製藥申請者尋求類似的和解？

Thanks, Graham. First, on Zolgensma, as I explained on the dynamics, I think the key drivers here are going to be the continued penetration in the incident population where our goal will be, in the United States, to achieve very high coverage of incident patients, both in newborn screening or those identified later on after newborn screening to continue to drive switches. And it's important to note that while we have covered a portion of the prevalent patients to date, because we haven't reached the highest levels of coverage within the incident population, there will continue to be opportunities for switches for Zolgensma, we expect, in the coming year. And that's a second source of business.

謝謝，格雷厄姆。首先，在 Zolgensma 上，正如我在動態中解釋的那樣，我認為這裡的關鍵驅動因素將是在事件人群中的持續滲透，我們的目標是在美國實現非常高的事件患者覆蓋率，既在新生兒篩查中或在新生兒篩查後確定繼續驅動開關的那些。重要的是要注意，雖然我們迄今為止已經覆蓋了一部分流行患者，但由於我們還沒有達到事件人群中的最高覆蓋水平，我們預計在來年。這是第二個業務來源。

The third will be the global launch, which we hope to achieve in -- to enable us to go into Europe and other markets. You'll, I think, likely note from the competitor sales as well, there are substantial sales opportunities outside the United States. We continue to prepare and develop those markets. I think our ability to launch in Europe, the Middle East, eventually in Latin America and Asia, will provide an important opportunity for Zolgensma IV.

第三個將是全球發布，我們希望實現這一目標——使我們能夠進入歐洲和其他市場。我認為，您可能也會從競爭對手的銷售中註意到，在美國以外也有大量的銷售機會。我們繼續準備和開發這些市場。我認為我們在歐洲、中東、最終在拉丁美洲和亞洲推出的能力將為 Zolgensma IV 提供重要機會。

And then lastly, of course, once we clarify the final filing and time lines, we'll provide further guidance on the intrathecal formulation and when we would expect that launched. So overall, I think a lot of catalysts coming for Zolgensma, a lot of positive momentum and energy around the data, a lot of interest from the physician and patient communities around the world. So we are confident in our longer-term outlook for this medicine.

最後，當然，一旦我們弄清了最終申請和時間表，我們將就鞘內製劑以及我們預計何時推出提供進一步的指導。所以總的來說，我認為 Zolgensma 有很多催化劑，圍繞數據的大量積極勢頭和能量，來自世界各地的醫生和患者社區的很多興趣。因此，我們對這種藥物的長期前景充滿信心。

Now with respect to Gilenya. With respect to the recent court injunction, which now covers all generic manufacturers, I think that's what you're referring to, when you look at any potential settlements, we're not disclosing any details of those settlements. Those discussions, of course, are ongoing. But just to remind everyone, we would expect at some point next year a ruling from the District Court -- or the start of a trial with the District Court, which will be important as well as the ruling on the appeal of the IPR ruling. Those are the next milestones with respect to Gilenya, but we feel very confident with our position, given the language used in the initial IPR ruling, the strength of our recent restraining order that was put in place. And so I think overall, we feel good about where we are in this process.

現在關於 Gilenya。關於最近的法院禁令，現在涵蓋所有仿製藥製造商，我認為這就是你所指的，當你查看任何潛在的和解時，我們不會透露這些和解的任何細節。當然，這些討論正在進行中。但提醒大家，我們預計明年某個時候地方法院會做出裁決——或者開始與地方法院進行審判，這與對知識產權裁決上訴的裁決一樣重要。這些是 Gilenya 的下一個里程碑，但我們對我們的立場非常有信心，考慮到最初的知識產權裁決中使用的語言，以及我們最近實施的限制令的力度。所以我認為總的來說，我們對自己在這個過程中所處的位置感覺良好。

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

我們的下一個問題來自 Jefferies 的 Peter Welford。

Firstly, just with regards to Zolgensma, I guess, following up in terms of the commentary that 4Q will be broadly in line. I guess given that you've seen a roughly similar split of incident versus prevalent patients, if I understand right, in the third quarter, presumably, there's still quite a large prevalent population of less than 2 years old left to be treated in the U.S. So I guess I'm just curious what is it at the moment that's the main factor to getting those patients on drug, given the broad access that you seem to have secured? And can you help us think about perhaps how we should think about that access improving during the course of 2020?

首先，我想就 Zolgensma 而言，根據評論 4Q 將大致一致。我想鑑於你已經看到了大致相似的事件與流行患者的分裂，如果我理解正確的話，在第三季度，大概還有相當多的不到 2 歲的流行人口在美國接受治療。所以我想我很好奇，鑑於您似乎已經獲得了廣泛的使用權，目前讓這些患者服藥的主要因素是什麼？您能否幫助我們思考，也許我們應該如何考慮在 2020 年期間改善訪問？

And then just moving on for a minute to Piqray. Obviously, a pretty impressive second quarter sales number there. I wonder if you can just talk about the testing rates that you're seeing at the moment. And give us some sort of idea in terms of, I guess, the coverage and the type of patients you're getting on Piqray at the moment, whether those patients are sort of last line or whether you're seeing earlier use driven by positive companion diagnostic tests?

然後繼續前進一分鐘到 Piqray。顯然，第二季度的銷售數字令人印象深刻。我想知道你是否可以談談你目前看到的測試率。並給我們一些想法，我猜，你目前在 Piqray 上接受的患者的覆蓋範圍和類型，這些患者是否是最後一線，或者你是否看到早期使用由積極驅動伴隨診斷測試？

Thanks for the questions, Peter. So on Zolgensma, in terms of the -- you're correct that we continue to have a prevalent population available to us. And because again, we are still climbing in our coverage of the incident population, every time we don't capture an incident patient, they become part of a prevalent pool that remains available to us for a period of time. So that dynamic, we think, will continue for some period until we achieve our goals of having very high coverage of the incident population.

謝謝你的問題，彼得。所以在 Zolgensma 上，就——你是正確的，我們繼續有一個普遍的人口可供我們使用。再次因為，我們對事件人群的覆蓋範圍仍在攀升，每當我們沒有捕獲到事件患者時，他們就會成為我們在一段時間內可用的流行池的一部分。因此，我們認為，這種動態將持續一段時間，直到我們實現對事件人口進行高覆蓋率的目標。

Now in terms of the dynamics on the prevalent population in switches, there's a combination of factors. I think, one, it's just continuing to work on the access environment, particularly in Medicaid. We're at 30%. Our goal is to increase that now over the course of next year, and that should enable us, hopefully, to be even more successful in the prevalent population.

現在，就交換機中普遍人口的動態而言，存在多種因素。我認為，第一，它只是繼續在訪問環境上工作，特別是在醫療補助計劃中。我們是 30%。我們的目標是在明年的過程中增加現在的數量，這應該使我們有希望在普遍人群中取得更大的成功。

Second is to continue the journey on patient and physician education, particularly around our long-term data. I think the only reasons we hear any reluctance to make the switch is because typically right now insurers are not covering both medicines. So if you make the switch, you are making the switch on to the gene therapy. And so continuing to educate physicians and patients on it, but we're seeing, I think, very strong uptake with respect to that as well. I think those are the 2 key dynamics, access and the continuing patient advocacy and education.

其次是繼續患者和醫生教育之旅，特別是圍繞我們的長期數據。我認為我們聽到不願進行轉換的唯一原因是因為現在保險公司通常不會同時承保這兩種藥物。所以，如果你做出改變，你就開啟了基因治療。因此，繼續就此對醫生和患者進行教育，但我認為，我們也看到了對此的強烈接受。我認為這是兩個關鍵動力，即獲取和持續的患者宣傳和教育。

And now in terms of the access dynamics, as I think I've already described, we have very good coverage in the private. Public should climb, and our focus right now is to continue to push the uptake of newborn screening.

現在就訪問動態而言，正如我想我已經描述的那樣，我們在私人領域有很好的覆蓋範圍。公眾應該攀升，我們現在的重點是繼續推動新生兒篩查的普及。

Piqray, I'll hand it over to Susanne.

Piqray，我會把它交給 Susanne。

Thank you, Vas. Thank you, Peter, for the questions. Actually, we're very excited about our launch in Piqray. As you know, these patients that have a PIK3CA mutation usually have a very poor prognosis. So we see very high interest, a very positive feedback from physicians. We have reached 49 million year-to-date and have more than 1,000 patients that receive Piqray now. In terms of coverage, we see very broad coverage for the treatment but also for the testing. As you know, Piqray as treatment but also PIK3CA testing is covered in the NCNN (sic) [NCCN] guidelines. And we are very pleased also with the uptake of the testing rates.

謝謝你，瓦斯。彼得，謝謝你提出的問題。實際上，我們對在 Piqray 中的發布感到非常興奮。如您所知，這些具有 PIK3CA 突變的患者通常預後很差。所以我們看到了非常高的興趣，來自醫生的非常積極的反饋。迄今為止，我們已經達到了 4900 萬，現在有超過 1000 名患者接受了 Piqray。在覆蓋範圍方面，我們看到治療的覆蓋範圍非常廣泛，而且測試的覆蓋範圍也非常廣泛。如您所知，NCNN (sic) [NCCN] 指南中涵蓋了 Piqray 作為治療方法以及 PIK3CA 測試的內容。我們也對檢測率的提高感到非常高興。

Specific to your question, what patients are currently treated on Piqray? Well, there might be a few patients that are in later line. But as you know, this is metastatic breast cancer patients with poor prognosis, so we expect that the majority of patients come really from second-line treatment. And we expect continued demand and are very pleased with the performance so far.

具體到您的問題，目前有哪些患者在 Piqray 上接受治療？好吧，可能有一些病人排在後面。但如您所知，這是轉移性乳腺癌患者，預後較差，因此我們預計大多數患者確實來自二線治療。我們預計會有持續的需求，並對迄今為止的表現感到非常滿意。

Thank you, Susanne. And we're very excited about taking Piqray into additional indications over time as well.

謝謝你，蘇珊娜。隨著時間的推移，我們也很高興將 Piqray 用於其他適應症。

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

我們的下一個問題來自高盛的 Keyur Parekh。

Two questions, please. One, Vas, as you talk about the momentum for the business into the 9 months of this year, can you help us think about how you see that momentum developing into 2020? What might be things that might accelerate versus what might be things that might pull you back into next year? That's question number one.

請教兩個問題。第一，瓦斯，當你談到今年 9 個月的業務發展勢頭時，你能幫我們想想你如何看待這種發展到 2020 年的勢頭嗎？哪些事情可能會加速，哪些事情可能會讓你回到明年？這是第一個問題。

And then question number two, coming back to Zolgensma, can you give us a sense for how much of that $160 million was from U.S. versus ex U.S? And how should we think about the reimbursement speed in the ex U.S. markets for next year?

然後是第二個問題，回到 Zolgensma，你能告訴我們這 1.6 億美元中有多少來自美國和美國以外嗎？我們應該如何考慮明年美國以外市場的報銷速度？

Thank you, Keyur. So on 2019 versus 2020 dynamics, as Harry described some of the dynamics for Q4, I think you'll have a similar set of factors that will impact us in 2020. On the one hand, you're going to see our launches, we'll continue to drive with great energy and as well as our growth drivers. We'll continue the strong productivity programs, where our goal has been to deliver $2 billion in absolute savings across NTO, our manufacturing as well as procurement as well as Business Services. But at the same time, we have in oncology a set of potential generics or generics that have already of course launched, primarily Afinitor, Exjade -- Exjade, Jadenu, I think are the ones highest on our mind. So I think we'll just have to see how those dynamics play out, but we think we'll set up well for a strong 2020 as well and we look forward to providing full year guidance in January.

謝謝你，基爾。因此，關於 2019 年與 2020 年的動態，正如 Harry 描述的第四季度的一些動態，我認為您將有一組類似的因素會在 2020 年影響我們。一方面，您將看到我們的發布，我們將繼續以巨大的能量和增長動力驅動。我們將繼續執行強大的生產力計劃，我們的目標是在 NTO、我們的製造、採購以及商業服務部門實現 20 億美元的絕對節省。但與此同時，我們在腫瘤學方面擁有一系列潛在的仿製藥或當然已經推出的仿製藥，主要是 Afinitor 、 Exjade -- Exjade 、 Jadenu ，我認為是我們心中最重要的。所以我認為我們只需要看看這些動態如何發揮作用，但我們認為我們也將為強勁的 2020 年做好準備，我們期待在 1 月份提供全年指導。

Now with respect to Zolgensma, what I can say, I think I would -- probably the accurate thing to say, is the vast majority of sales come from the U.S. We have had paid patients from select European countries that have put already in place programs. Of course, the French ATU is one such program, but there are other countries that have already reimbursed patients, including Portugal and Germany, amongst others. There is broad reimbursement right now for nusinersen in Europe. So we are, of course, endeavoring to have rapid -- as rapid as possible reimbursement uptake as we can. We think there will be strong advocacy for the use of Zolgensma, and we think we can make very compelling cost-effectiveness arguments for payers in Europe and other parts of the world with the medicine that hopefully will enable rapid access and rapid reimbursement.

現在關於 Zolgensma，我能說的，我想我會 - 可能是準確的說法是，絕大多數銷售來自美國。我們已經支付了來自特定歐洲國家的患者，這些國家已經實施了計劃.當然，法國的 ATU 就是這樣一個項目，但還有其他國家已經為患者報銷，包括葡萄牙和德國等。現在歐洲對 nusinersen 有廣泛的報銷。因此，我們當然會努力盡快——盡可能快地接受報銷。我們認為 Zolgensma 的使用將會得到強烈的支持，我們認為我們可以為歐洲和世界其他地區的付款人提出非常有說服力的成本效益論據，希望這種藥物能夠實現快速獲取和快速報銷。

Our next question comes from the line of Andrew Baum from Citigroup.

我們的下一個問題來自花旗集團的 Andrew Baum。

I'm not sure if John Tsai is on the line, but I'd be curious as to his view. Both yourselves with Entresto and Biogen with aducanumab are filing data on subgroups from 2 trials which failed to hit their primary endpoint. In the context of some recent comments from Bob Temple, should we be thinking of this as the beginning of a new paradigm in willingness of the FDA to go further with subgroup analysis than they may have done previously in terms of trials which failed to meet?

我不確定 John Tsai 是否在線，但我很好奇他的觀點。你們自己的 Entresto 和 Biogen 的 aducanumab 都在提交 2 項未能達到主要終點的試驗的亞組數據。在 Bob Temple 最近發表的一些評論的背景下，我們是否應該將此視為 FDA 願意進一步進行亞組分析的新範例的開始，而不是他們之前在未能滿足的試驗方面所做的？

And then second, on Cosentyx, looking at the IQVIA data, the drug seems to have stalled in terms of both NRx and TRx approximately since the launch the launch of Skyrizi. Is there some issue with sampling here? Or is there something else going on to explain the paradoxical outlook?

其次，在 Cosentyx 上，查看 IQVIA 數據，自 Skyrizi 推出以來，該藥物在 NRx 和 TRx 方面似乎都停滯不前。這裡的採樣有問題嗎？還是有其他事情可以解釋這種矛盾的觀點？

Yes. Thank you, Andrew. So on Entresto, John?

是的。謝謝你，安德魯。那麼在 Entresto 上，約翰？

Yes. Thanks for the question, Andrew. I think it's very insightful you picked up some of the deliberations from Bob Temple. I think, one, when we look at Entresto and the results, obviously, we talked about the heart failure with preserved ejection fraction population that currently has no treatment. So given that's the underlying basis, we are having discussions with the agency, and they have expressed interest in seeing the results. So we'll have continued dialogue with them in terms of the best way to move forward. And we'll submit those before the end of the year. That's the approach we'll take for Entresto.

是的。謝謝你的問題，安德魯。我認為你從鮑勃·坦普爾 (Bob Temple) 那裡汲取了一些審議意見，很有見地。我想，第一，當我們看 Entresto 和結果時，很明顯，我們談到了目前沒有治療的射血分數保留的心力衰竭人群。因此，鑑於這是基礎，我們正在與該機構進行討論，他們表示有興趣看到結果。因此，我們將繼續與他們就前進的最佳方式進行對話。我們將在年底前提交這些文件。這就是我們為 Entresto 採取的方法。

And if I could just add, I think one important element -- I can't comment on the other filing you mentioned. But I think on Entresto, one important element is this is an approved medicine in reduced ejection fraction heart failure with a sizable safety database and a patient population that we studied that's adjacent to the original patient population and, I would say, also with unclear boundaries. The 40% ejection fraction versus 60% ejection fraction, where do we cross the line from reduced ejection fraction to preserved ejection fraction? It's notable, 35% used to be the cutoff, and we've moved to 40% for reduced ejection fraction. So we're in a gray zone here. And I think that's part of the reason we believe the regulators encouraged us to file the data and then take the next steps because there may be ways to look at this to enable patients to benefit, particularly building off an approved medicine with a long track record.

如果我可以補充一點，我認為有一個重要因素——我不能對你提到的另一份文件發表評論。但我認為在 Entresto 上，一個重要的因素是這是一種經批准的用於降低射血分數心力衰竭的藥物，具有相當大的安全性數據庫和我們研究的患者群體與原始患者群體相鄰，而且我想說，邊界也不明確.40% 的射血分數與 60% 的射血分數，我們在哪裡越過從減少的射血分數到保留的射血分數的界限？值得注意的是，過去 35% 是臨界值，而我們已經移動到 40% 以降低射血分數。所以我們在這里處於灰色地帶。我認為這就是我們相信監管機構鼓勵我們提交數據然後採取後續步驟的部分原因，因為可能有一些方法可以查看此數據以使患者受益，特別是建立具有長期記錄的已批准藥物.

Now with respect to Cosentyx NRx, Marie-France?

現在關於 Cosentyx NRx，Marie-France？

So actually, we're delighted with our performance with Cosentyx. It's growing strongly, actually faster than the market in dermatology and rheumatology. It's normal for us to see some of these fluctuations in NBRx, but if we look across the year, the NBRx is very solid. In the U.S., we're actually growing twice the market in both derm and rheum. Skyrizi is expanding the market, as other launches have done, but it's taking share from older agents, namely the anti-TNFs. Cosentyx is actually more than just a great dermatology drug, it's a complete treatment. 2/3 of the patients have additional manifestations beyond skin, and given the complete treatment or a strong first-line access, we're confident in the potential of this product going forward.

所以實際上，我們對 Cosentyx 的表現感到滿意。它增長強勁，實際上比皮膚病學和風濕病學市場增長得更快。我們看到 NBRx 出現這些波動是正常的，但如果我們縱觀全年，NBRx 非常穩定。在美國，我們在真皮和大黃方面的市場增長實際上是兩倍。Skyrizi 正在擴大市場，就像其他上市公司所做的那樣，但它正在從老牌藥物（即抗 TNF 藥物）那里奪取市場份額。Cosentyx 實際上不僅僅是一種出色的皮膚病藥物，它還是一種完整的治療方法。2/3 的患者有皮膚以外的其他表現，並且考慮到完整的治療或強大的一線訪問，我們對該產品未來的潛力充滿信心。

Yes. And if I could just highlight again, we've looked, I think, tried to look as carefully as we can about the dynamics. And when we looked at the NBRx data and the TRx data across -- in dermatology, we feel very good about the trend set that we're seeing. And we'll look forward to continuing to demonstrate that in quarter 4 and then into 2020.

是的。如果我可以再次強調，我認為我們已經盡可能仔細地了解動態。當我們在皮膚病學領域查看 NBRx 數據和 TRx 數據時，我們對所看到的趨勢集感到非常滿意。我們期待在第 4 季度和 2020 年繼續證明這一點。

Our next question comes from the line of Eric Le Berrigaud from Bryan Garnier.

我們的下一個問題來自 Bryan Garnier 的 Eric Le Berrigaud。

First question is about amortizations of intangible in pharma. There are some significant swings here. In the third quarter, it was significantly up. Going forward, what should we expect? Is it the first sign of AveXis of a full quarter being fully amortized? And so should we expect $700 million to $750 million per quarter to persist over the coming quarters?

第一個問題是關於製藥業無形資產的攤銷。這裡有一些顯著的波動。在第三季度，它顯著上升。展望未來，我們應該期待什麼？這是 AveXis 一個完整季度被完全攤銷的第一個跡象嗎？那麼我們是否應該期望在接下來的幾個季度中每季度持續 7 億至 7.5 億美元？

And the second question is about Entresto. My understanding is that in the U.S., you suffered from some negative inventory movements. Could you quantify that for the second quarter and maybe give some explanation whether it corresponds to any price increase or some rebate discounts in anticipation for that or these kind of things?

第二個問題是關於 Entresto 的。我的理解是，在美國，你遭受了一些負庫存變動。你能否量化第二季度的情況，並給出一些解釋，說明它是否對應於任何價格上漲或一些預期的回扣折扣？

Thank you, Eric. On amortization of intangibles, Harry?

謝謝你，埃里克。關於無形資產的攤銷，Harry？

Yes. Eric, so amortization of intangibles, of course, what you see is the acquired medicines, so to say, to increase the amortization piece according to the expected [remaining] patent life that we assume in the accounting according to IFRS. So we have AveXis and we have Xiidra coming in which added, of course, then to the amortization. So that's the level of amortization I would expect going forward. Of course, always pending potential M&A actions, right, which then would add to it. And of course, over time some of the older assets would come off, but that's right now roughly the level that we see also going forward.

是的。埃里克，所以無形資產的攤銷，當然，你看到的是收購的藥品，可以說，根據我們根據國際財務報告準則在會計中假設的預期[剩餘]專利壽命增加攤銷。所以我們有 AveXis，我們有 Xiidra 進來，當然，然後加入攤銷。這就是我期望的攤銷水平。當然，總是在等待潛在的併購行動，對吧，然後會增加它。當然，隨著時間的推移，一些較舊的資產會脫落，但現在大致就是我們看到的未來水平。

Thanks, Harry. And then on Entresto dynamics, Marie-France?

謝謝，哈利。然後是關於 Entresto 動態，Marie-France？

So we have seen some seasonal effect in Q3, but this is completely in line with previous years. We'll always see some stock and trade fluctuations and we have seen some revenue reduction true-ups in Q3. However, if we look at demand, it's really strong. Our TRxs are up 50% year-over-year. We are expecting a really strong Q4 and we're comfortable with our full year consensus.

所以我們在第三季度看到了一些季節性影響，但這與往年完全一致。我們總是會看到一些股票和貿易波動，並且我們已經看到第三季度的收入減少了一些。但是，如果我們看一下需求，它確實很強勁。我們的 TRx 同比增長 50%。我們期待一個非常強勁的第四季度，我們對我們的全年共識感到滿意。

And maybe, Harry, you want to just dimensionalize, just a look at the question on inventory versus revenue deduction?

也許，Harry，你只想維度化，看看關於庫存與收入扣除的問題？

Yes. It's roughly half-half. Also, on the inventory, I just want to reassure you, this is sometimes 1 or 2 days of inventory we talk here. Overall, there's hardly any fluctuation on the company or the key brands that would be any cause of concern. It's one of our key control as you know, each quarter, each month to ensure that we see overall sales in line with demand. So when a couple of effects come together, like a bit of revenue reduction and maybe 1 or 2 days less stock in trade, that month you have a bit of an effect, especially as we also have in quarter 3 always a bit lower new scripts on Entresto. So nothing to be concerned about. Very strong underlying demand.

是的。大概是一半一半。另外，關於庫存，我只是想向您保證，這有時是我們在這裡談論的 1 或 2 天的庫存。總體而言，公司或主要品牌幾乎沒有任何值得關注的波動。如您所知，這是我們每個季度、每個月的關鍵控制之一，以確保我們看到整體銷售符合需求。因此，當一些影響結合在一起時，比如收入減少一點，貿易庫存可能減少 1 或 2 天，那個月你會產生一些影響，尤其是我們在第 3 季度也總是有一點點新腳本在 Entresto 上。所以沒有什麼可擔心的。非常強勁的潛在需求。

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

我們的下一個問題來自瑞士信貸的 Matthew Weston。

Two questions, if I can. The first is on Zolgensma and the strong data. Vas, I think you said that after we'd seen the second dose you would discuss with FDA whether that was sufficient for filing or whether or not we had to wait for the highest-dose data. I wonder whether those conversations have now been had post-World Muscle and what the decision was between waiting for that third dose?

兩個問題，如果可以的話。首先是關於 Zolgensma 和強大的數據。Vas，我想你說過，在我們看到第二劑之後，你會與 FDA 討論這是否足以提交，或者我們是否必須等待最高劑量的數據。我想知道這些談話現在是否已經發生在世界肌肉之後，以及等待第三劑之間的決定是什麼？

And then secondly, a question around share buybacks. Clearly, the cash flow remains extraordinarily strong with a very strong earnings growth at the business. Obviously, the Alcon -- or the program associated with limiting the dilution of Alcon is now complete. But I wondered philosophically how you felt about further additional share buybacks.

其次，關於股票回購的問題。顯然，現金流仍然非常強勁，業務盈利增長非常強勁。顯然，愛爾康——或與限制愛爾康稀釋相關的計劃現已完成。但我從哲學上想知道你對進一步額外的股票回購有何看法。

And then if I can cheat a quick third one, Harry. A feature of Q2 was writing back prelaunch inventory and it had a very meaningful impact on margins. I wondered if we were going to see something similar with Beovu in 4Q.

然後，如果我能快速作弊，第三個，哈利。第二季度的一個特點是回寫上市前庫存，它對利潤率產生了非常有意義的影響。我想知道我們是否會在第四季度看到與 Beovu 類似的東西。

Thank you, Matthew. So first on Zolgensma, we submitted the data to FDA with respect to the first 2 doses that we presented at WMS. And we still have not had the conversation yet with FDA. As soon as we have that conversation and can clarify the filing approach, we'll provide that. And I would say as well, we are making progress as well on the high-dose if it is in fact, needed. But our position is that we have data needed and we'll hopefully have that conversation with FDA in a positive way. With respect to share buybacks, Harry?

謝謝你，馬修。因此，首先在 Zolgensma 上，我們向 FDA 提交了我們在 WMS 上展示的前兩劑數據。我們還沒有與 FDA 進行對話。一旦我們進行了對話並且可以澄清歸檔方法，我們就會提供。我還要說的是，如果確實需要的話，我們也在高劑量方面取得了進展。但我們的立場是我們有所需的數據，我們希望以積極的方式與 FDA 進行對話。關於股票回購，Harry？

Thank you, Matthew, and also for noting the strong free cash flow we have which is always of course a key focus area for us and we are doing quite well. Always improvement areas of course, but wonderful $9.4 billion, the first 9 months, so going well there. And overall, share buybacks, I continue -- we continue to see share buybacks as part of our capital allocation priorities, but it's also #4. So after we have completed this one, the $5 billion that we announced last year in June, we completed in quarter 3, we of course continue to look at our capital overall. And just to remind everybody on the phone, after the first priority being organic investment, the second being strong and growing dividend and third being bolt-on up to basically 5% of our market cap, the fourth is share buybacks. And so we will continue to evaluate this as we go forward. In case we would have specific share buyback program to lower the underlying share count, we would make an announcement publicly. We have an ongoing commitment to mitigate any diluting effect from our employee participation programs, so you will see ongoing some share buybacks as we buy back employee shares. So let's see. It will continue to be part of the future capital allocation priorities, but it's #4. And we would always announce when we do a specific one.

謝謝你，Matthew，也感謝你注意到我們擁有強勁的自由現金流，這當然一直是我們關注的重點領域，我們做得很好。當然，總是在改進領域，但前 9 個月的 94 億美元非常可觀，所以進展順利。總的來說，股票回購，我繼續——我們繼續將股票回購視為我們資本配置優先事項的一部分，但它也是#4。因此，在我們完成這一項目後，即我們去年 6 月宣布的 50 億美元，我們在第三季度完成後，我們當然會繼續關注我們的整體資本。只是想在電話中提醒大家，在第一優先是有機投資之後，第二是強勁且不斷增長的股息，第三是補強到我們市值的 5%，第四是股票回購。因此，我們將在前進的過程中繼續對此進行評估。如果我們有特定的股票回購計劃來降低基礎股票數量，我們會公開發佈公告。我們一直致力於減輕員工參與計劃的任何稀釋影響，因此您會在我們回購員工股票時看到持續的一些股票回購。讓我們看看。它將繼續成為未來資本配置優先事項的一部分，但它排在第四位。當我們做一個特定的事情時，我們總是會宣布。

And Harry, inventory movements on Beovu?

Harry，Beovu 上的存貨變動情況？

So this is the launch provision as we, prior to approval, write off any launch inventory according to prudent IFRS accounting rules. There will be some, but I don't see this -- that this would impact as you have seen before. So usually, our prelaunch inventory, the cost of goods are quite low. And therefore, you don't see these effects and they level out over years.

所以這是啟動條款，因為我們在批准之前根據審慎的 IFRS 會計規則註銷任何啟動庫存。會有一些，但我不認為這會像您之前看到的那樣產生影響。所以通常情況下，我們的預售庫存，商品成本非常低。因此，您看不到這些影響，並且它們會隨著時間的推移而趨於平穩。

Maybe I'll take the opportunity, Marie-France, do you want to provide some color of the conversation you had, Beovu at AAO and some of the excitement that you saw on the product?

也許我會抓住機會，Marie-France，你想提供一些關於你在 AAO 的 Beovu 談話的色彩以及你在產品上看到的一些興奮嗎？

Yes. So we're very thrilled about the feedback we got at AAO. We spent some time there and obviously met with some of the top retina specialists in the U.S. I mean what we're hearing from physicians is they really make their decisions on the ability of a medicine to dry better on the dosing interval, on the safety and on the cost. And what we know with Beovu is that we really believe we've got a product that can deliver on these 4 dimensions, providing greater fluid resolution, longer intervals for patients, uncompromised safety. And definitely, what we've heard from AAO is that physicians were very impressed on how we priced the product. We really got great feedback. They're excited to use Beovu and want to treat patients quickly. A lot of them described Beovu, and I'll just use a quote, as a "generational leap." So we're very excited. We believe Beovu will be a major player in the wet AMD space and beyond.

是的。因此，我們對在 AAO 獲得的反饋感到非常興奮。我們在那里呆了一段時間，顯然會見了美國的一些頂級視網膜專家。我的意思是我們從醫生那裡聽到的是，他們真的根據藥物在給藥間隔、安全性方面更好地干燥的能力做出決定和成本。我們對 Beovu 的了解是，我們真的相信我們擁有可以提供這四個維度的產品，提供更高的流體分辨率、更長的患者間隔時間和毫不妥協的安全性。當然，我們從 AAO 那裡聽到的是，醫生對我們為產品定價的方式印象深刻。我們真的得到了很好的反饋。他們對使用 Beovu 感到興奮，並希望快速治療患者。他們中的很多人將 Beovu 描述為“代際飛躍”，我只引用一句。所以我們非常興奮。我們相信 Beovu 將成為濕 AMD 領域及其他領域的主要參與者。

Great, thank you Marie-France. So we'll keep working to demonstrate that in the coming quarters.

太好了，謝謝 Marie-France。因此，我們將在未來幾個季度繼續努力證明這一點。

And our next question comes from the line of Steve Scala from Cowen.

我們的下一個問題來自 Cowen 的 Steve Scala。

Two questions. First, on Zolgensma. It was launched with a pay-for-performance program. What portion of dosed patients have fully achieved the necessary milestones required by the pay-for-performance program so any clawback is now not possible? That's the first question.

兩個問題。首先，關於 Zolgensma。它是通過按績效付費計劃推出的。有多少接受劑量的患者已完全達到按績效付費計劃所需的必要里程碑，因此現在不可能進行任何回扣？這是第一個問題。

Second question is on fevipiprant. What can you say about the performance on FEV1? Was it just inconsistent? Or was it a complete miss? It would seem less likely that a drug that fails on FEV1 hits on exacerbations. [Kalyd] did that just that, but its FEV1 data was inconsistent and not a complete miss.

第二個問題是關於fevipiprant。您對 FEV1 的表現有何看法？只是不一致嗎？還是完全錯過了？一種在 FEV1 上失敗的藥物似乎不太可能出現急性加重。[Kalyd] 就是這樣做的，但它的 FEV1 數據不一致，並非完全失誤。

Thanks, Steve. On Zolgensma pay-for-performance, what I can say is we have that feature and many if not all of our contracts with private insurers. I think very few, if any, have yet met the milestones associated with those contracts. I would say as well, though, that we have now presented data with patients out beyond 5 years, maintaining all motor milestones. The average patient now from the START Study is beyond 4 years of age, and we continue not to see deterioration in the motor milestones gained in those patients treated with Zolgensma.

謝謝，史蒂夫。關於 Zolgensma 按績效付費，我能說的是我們有這個功能，而且我們與私人保險公司簽訂的合同如果不是全部，也有很多。我認為很少有人（如果有的話）達到與這些合同相關的里程碑。不過，我還要說的是，我們現在已經提供了超過 5 年的患者數據，保持所有運動里程碑。現在 START 研究的平均患者年齡超過 4 歲，我們繼續沒有看到接受 Zolgensma 治療的患者獲得的運動里程碑出現惡化。

If I just add, Steve, on the revenue recognition principals, of course, on the very small portion of patients that would be on that pay-for-performance. We ensure that we have appropriate revenue deductions from a statistical model so to say, which initially we have from the clinical trials and which we would update every quarter, according to real-world, which we expect to be close to [clinical] trials. So revenue deductions are already taking this into account and are very prudently managed.

如果我只是補充，史蒂夫，關於收入確認原則，當然，對於極少數按績效付費的患者。我們確保我們從統計模型中有適當的收入扣除，可以說，我們最初從臨床試驗中獲得，並且我們將根據現實世界每季度更新一次，我們預計這將接近 [臨床] 試驗。因此，收入扣除已經考慮到這一點，並且得到了非常謹慎的管理。

John, on the fevipiprant ZEAL?

約翰，關於熱情的 ZEAL？

Thanks for the question, Steve. I'm not going to go into the details of the fevipiprant study results. But what I will say is that we're currently in the process of really analyzing the results. And one bit of color on it is, we're not surprised by the results that we received in the ZEAL 1 and 2 studies. As you know, these studies were conducted in a moderate asthma patient population and that was across a broad unselected population and it was not stratified by eosinophil count. So that was the basis.

謝謝你的問題，史蒂夫。我不打算詳細介紹 fevipiprant 研究結果。但我要說的是，我們目前正在真正分析結果。有點顏色的是，我們對 ZEAL 1 和 2 研究中收到的結果並不感到驚訝。如您所知，這些研究是在中度哮喘患者人群中進行的，並且涵蓋了廣泛的未經選擇的人群，並且沒有根據嗜酸性粒細胞計數進行分層。這就是基礎。

Our original intent in terms of filing was always looking at the severe population and especially looking at the elevated eosinophil count. Given that that's our focus, we'll look forward to sharing the results in the first quarter as well as sharing the results of LUSTER 1 and 2, which will form the basis of our filing in the first quarter of next year.

我們提交申請的初衷一直是關注重症人群，尤其是嗜酸性粒細胞計數升高的人群。鑑於這是我們的重點，我們期待在第一季度分享結果以及分享 LUSTER 1 和 2 的結果，這將構成我們明年第一季度提交申請的基礎。

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

我們的下一個問題來自法國興業銀行的 Florent Cespedes 系列。

Two quick ones. First on respiratory. Could we have your view on the respiratory franchise strategy going forward given the fevipiprant results and the [ENL] products approvals expected next year? And if you can explain the situation in Europe versus the situation and your strategy in the U.S.?

兩個快的。首先是呼吸。鑑於 fevipiprant 結果和預計明年的 [ENL] 產品批准，我們能否對未來的呼吸系統特許經營策略發表看法？如果你能解釋歐洲的情況與美國的情況和你的戰略？

Second question for Harry on the Sandoz margin. How sustainable is the Sandoz operating profit margin improvement? How should we extrapolate the Q3 performance? Or in other words, what is the underlying growth or operating profit improvement for Sandoz this quarter?

關於 Sandoz 邊緣的哈利的第二個問題。Sandoz 營業利潤率提高的可持續性如何？我們應該如何推斷第三季度的表現？或者換句話說，山德士本季度的潛在增長或營業利潤改善情況如何？

Thank you, Florent. I just want to say it's ladies and gentlemen now, at least for Novartis, so we have almost 50-50 representation in the room. So on the respiratory franchise, I think when you look at it, we have positive results now for QVM, the triple in asthma as well as QMS, which would be a LABA ICS in asthma. That would be built on top of Ultibro, which is our LABA/LAMA in COPD. So we have a broad portfolio of inhaled medicines, and we are now looking at the optimal way to launch that entire respiratory portfolio.

謝謝你，弗洛倫特。我只想說現在是女士們先生們，至少對於諾華公司來說是這樣，所以我們在房間裡有近 50-50 名代表。因此，在呼吸專營權方面，我認為當你看它時，我們現在對 QVM、哮喘的三重以及 QMS 取得了積極的結果，這將是哮喘的 LABA ICS。那將建立在 Ultibro 之上，這是我們在 COPD 中的 LABA/LAMA。因此，我們擁有廣泛的吸入藥物組合，我們現在正在尋找推出整個呼吸系統產品組合的最佳方式。

Clearly, the final results from fevipiprant will shape a lot of our thinking. Our overall strategy in respiratory was to move towards more specialty respiratory and severe respiratory, building on our strength from Xolair. And our ideal positioning would be to have Xolair, fevipiprant, then having QVM as an option for patients before they move on to the more advanced therapy. So we'll see how that evolves. We continue to have a research program looking at diseases like IPF, sarcoidosis, pulmonary arterial hypertension as well. I think we'll have a better view on our longer-term outlook in the respiratory franchise in 2020. Now with respect to Sandoz and margins, Richard?

顯然，fevipiprant 的最終結果將影響我們的很多想法。我們在呼吸系統方面的總體戰略是在 Xolair 的優勢基礎上，轉向更專業的呼吸系統和嚴重呼吸系統。我們理想的定位是先使用 Xolair、fevipiprant，然後再將 QVM 作為患者的一種選擇，然後再進行更先進的治療。所以我們將看看它是如何演變的。我們繼續開展一項研究計劃，以研究 IPF、結節病、肺動脈高壓等疾病。我認為我們將對 2020 年呼吸系統特許經營的長期前景有更好的看法。現在關於山德士和利潤率，理查德？

Thank you, Florent. The core op -- I mean, clearly there was exceptionally strong result for the quarter, reflecting good underlying performance, but also a noticeable impact of U.S. onetimers, particularly Medicaid gross-to-net adjustment. The core growth margin, really driven by favorable product mix, strong underlying growth from the Biologics business growing at 27% and the geographic mix, plus the ongoing transformation of productivity improvements as well as the positive impact of the Medicaid gross-to-net, partly offset clearly by the continued price erosion particularly we're seeing in the U.S. Our goal is to continue to drive margin improvements as we drive the operational focus. But clearly, we don't make specific forecasts. And in 2020, we'll give you guidance for going forward.

謝謝你，弗洛倫特。核心業務——我的意思是，顯然本季度的業績異常強勁，反映出良好的基本業績，但也反映了美國一次性產品的顯著影響，尤其是醫療補助計劃的毛淨調整。核心增長利潤率真正受到有利的產品組合、生物製品業務增長 27% 的強勁基礎增長和地域組合的推動，再加上生產率提高的持續轉型以及醫療補助總額對淨額的積極影響，部分被持續的價格侵蝕所抵消，尤其是我們在美國看到的。我們的目標是在推動運營重點的同時繼續推動利潤率的提高。但顯然，我們不做具體預測。在 2020 年，我們將為您提供前進的指導。

Great. Thank you, Richard. And Richard, any early perspectives on Sandoz and how you see things progressing?

偉大的。謝謝你，理查德。理查德，對 Sandoz 的任何早期觀點以及你如何看待事情的進展？

No. I mean clearly, we're on track with the Sandoz transformation. We have seen a very engaged organization that's very growth-orientated with a lot of work going on in terms of our supply chain, our alignment. And we are noting that transformation is really much on track, but this is a multiyear journey in terms of building a generic-focused business, which I look forward to talking to you about later.

不。我的意思是很清楚，我們正在推進 Sandoz 轉型。我們已經看到一個非常敬業的組織，它非常以增長為導向，在我們的供應鍊和我們的聯盟方面正在進行大量工作。我們注意到轉型確實已經步入正軌，但就建立以仿製藥為重點的業務而言，這是一個多年的旅程，我期待稍後與您討論。

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

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

Just going back to fevipiprant. Would you -- I guess you still sound quite bullish on the program. You did hit FEV1 in your Phase II trial. My question to you is, are you saying that the probability of success in hitting results in LUSTER are just as high now as they would have been before you knew the results of ZEAL? It seems to me that not showing an FEV1 benefit has to be a negative harbinger of sorts on what to expect from the next round of trials.

只是回到 fevipiprant。你——我想你聽起來仍然很看好這個項目。您在 II 期試驗中確實達到了 FEV1。我的問題是，您是說現在 LUSTER 取得成功的概率與您知道 ZEAL 的結果之前一樣高嗎？在我看來，沒有顯示出 FEV1 的好處一定是對下一輪試驗的預期結果的某種負面預兆。

And then just a quick question on Zolgensma. Just the number of patients treated, do we just simply take sales in the quarter divided by 2 million? Or can you actually give us the actual number of patients?

然後只是一個關於 Zolgensma 的快速問題。只是接受治療的患者人數，我們只是簡單地將本季度的銷售額除以 200 萬嗎？或者你能給我們實際的患者人數嗎？

Just on fevipiprant just to, I guess, clarify. When you go back to the Phase II studies, the DP2 class has been, I think, well studied also in our hands. When we studied mild-to-moderate patients in various contexts, we didn't see a -- we did see some FEV1 benefit. We didn't see a significant benefit. It was only when we studied patients in a publication we published at ERS a few years ago and that looked at high-use eosinophil patients that we saw the benefit. So I think it's important context. ZEAL 1 and 2, LUSTER 1 and 2 are very separate efforts. ZEAL 1 and 2 is looking at this mild population -- moderate population, I should say, not stratifying for eosinophil. LUSTER is looking at the severe population, looking at the high, primarily hopefully looking at it with a positive result in the high-use eosinophil population, as you've seen with the various Biologics. The ZEAL result is largely in line with what we saw in Phase II. It was requested of us as it's been requested of others to look at a less severe population. I don't think there's a read-through. I can't say we're more or less bullish about LUSTER 1 and 2. LUSTER 1 and 2 is just a different patient population.

就 fevipiprant 而言，我猜想澄清一下。當你回到第二階段的研究時，我認為 DP2 班級在我們手中也得到了很好的研究。當我們在不同情況下研究輕度至中度患者時，我們沒有看到——我們確實看到了 FEV1 的一些好處。我們沒有看到明顯的好處。只有當我們幾年前在 ERS 上發表的一篇出版物中研究患者時，我們才看到了這種益處，該出版物研究了高使用嗜酸性粒細胞患者。所以我認為這是重要的背景。ZEAL 1 和 2、LUSTER 1 和 2 是非常獨立的工作。ZEAL 1 和 2 正在研究這個輕度人群——中度人群，我應該說，不對嗜酸性粒細胞進行分層。LUSTER 正在研究嚴重人群，研究高人群，主要希望在高使用嗜酸性粒細胞人群中取得積極結果，正如您在各種生物製劑中看到的那樣。ZEAL 結果在很大程度上與我們在第二階段看到的一致。我們被要求這樣做，因為其他人也被要求研究不太嚴重的人群。我認為沒有通讀。我不能說我們或多或少看好 LUSTER 1 和 2。LUSTER 1 和 2 只是不同的患者群體。

With respect to Zolgensma, you'd have to divide the total sales by the net pricing that we've achieved and also look at our U.S.-EU mix. But you can think about we're in the range of 100 patients treated that currently under the paid program. We also, of course, have many patients that were previously treated in the Managed Access program as well as the ongoing clinical trials, but I think roughly 100 patients treated to date around the world is a reasonable number, give or take.

關於 Zolgensma，你必須將總銷售額除以我們實現的淨定價，還要查看我們的美國-歐盟組合。但是你可以考慮一下我們目前在付費項目下接受治療的 100 名患者。當然，我們也有許多患者以前在受管訪問計劃中接受過治療以及正在進行的臨床試驗，但我認為迄今為止全世界大約有 100 名患者接受治療是一個合理的數字，無論是給予還是接受。

Our next question comes from the line of Richard Parkes from Deutsche Bank.

我們的下一個問題來自德意志銀行的 Richard Parkes。

Firstly, I'm just trying to understand a little bit better the Mayzent onboarding issue. I'm just trying to understand why Mayzent would be any different from any other MS therapy. It sounds like reimbursement access isn't the issue here. So could you just confirm sort of the specifics there and whether it's a logistical issue rather than reimbursement access. So that's first question.

首先，我只是想更好地理解 Mayzent 入職問題。我只是想了解為什麼 Mayzent 與任何其他 MS 療法有任何不同。聽起來報銷權限不是這裡的問題。那麼你能否確認那裡的一些細節，以及它是否是一個後勤問題而不是報銷問題。這是第一個問題。

Then the second question, just on Cosentyx and non-radiographic axial spondyloarthritis. Obviously, penetration rates are partly low due to the lack of approved therapies in that setting. But I think biologic drugs have been available for a little bit longer in Europe. So can you discuss what experience in Europe tells us about the likely barriers to uptake in that setting and what you might be able to do to go about improving on those levels of penetration?

然後是第二個問題，關於 Cosentyx 和非放射學中軸型脊柱關節炎。顯然，滲透率較低的部分原因是該環境中缺乏批准的療法。但我認為生物藥物在歐洲的使用時間稍長一些。那麼，您能否討論歐洲的哪些經驗告訴我們在該環境中可能存在的吸收障礙，以及您可以做些什麼來提高這些滲透水平？

On Mayzent uptake, Marie-France?

關於 Mayzent 的吸收，Marie-France？

The NBRx that we see shows that physicians see the value in this product. We do see a 90-day lag between start forms and paid scripts and this is due to baseline testing and free drugs. However, now that we've been in the market for a couple of months, we do see opportunities to accelerate this. I think if I go back to what I said in Q2, we have always said that the first 12 months with Mayzent would be about education. Physicians recognize that these patients are progressing. The challenge is that they are not diagnosing SPMS, and that is because there've been no effective therapies until now. So this means we need to change habits, and that takes time. We're very committed to Mayzent because patients need it. It's really the only DMT with proven efficacy in this population, so we just need to work, continue to work on education and continue to work to accelerate the pull-through.

我們看到的 NBRx 表明醫生看到了該產品的價值。我們確實看到啟動表格和付費腳本之間有 90 天的滯後，這是由於基線測試和免費藥物。然而，既然我們已經進入市場幾個月，我們確實看到了加速這一進程的機會。我想如果回到我在第二季度所說的話，我們一直說 Mayzent 的前 12 個月將與教育有關。醫生認識到這些患者正在進步。挑戰在於他們沒有診斷出 SPMS，那是因為直到現在還沒有有效的治療方法。所以這意味著我們需要改變習慣，而這需要時間。我們非常致力於 Mayzent，因為患者需要它。它確實是唯一一種在這一人群中被證明有效的 DMT，所以我們只需要努力，繼續致力於教育，繼續努力加速實現。

I think one element that's specific to Mayzent is the need for a certain genetic testing, which we're now working to accelerate as well. That's just one component. But I think we really view this as a logistical operational challenge. We're seeing strong interest and strong demand from the patient physician community. Now on your question on non-radiographic axial SpA, you are correct there are TNFs that have been approved in the past in this indication in Europe. I think the key things for us are going to be making a strong access argument around the world in the U.S. and in Europe and then improving diagnosis rates. When you look at the diagnostic inclusion criteria, it does involve an MRI. And so I think one of the key things for us is going to be to work through patient -- physicians understanding how to identify patients that might be in what is really an early stage of ankylosing spondylitis, take the appropriate measures to evaluate the patient and then hopefully get them on the medicine.

我認為 Mayzent 特有的一個要素是需要進行某種基因測試，我們現在也在努力加快這一進程。那隻是一個組成部分。但我認為我們確實將其視為後勤運營挑戰。我們看到了來自患者醫師社區的濃厚興趣和強烈需求。現在關於非射線軸 SpA 的問題，你是對的，歐洲過去已經批准了 TNF 用於該適應症。我認為對我們來說關鍵的事情是在美國和歐洲在世界範圍內提出強有力的可及性論據，然後提高診斷率。當您查看診斷納入標準時，它確實涉及 MRI。因此，我認為對我們來說最重要的事情之一就是通過患者工作——醫生了解如何識別可能處於強直性脊柱炎早期階段的患者，採取適當的措施來評估患者和然後希望讓他們服藥。

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

我們的下一個問題來自摩根大通的 Richard Vosser。

So 2, please. First just going back to Sandoz. I wondered if you could give us the contribution from the oral solids business at the 9 months, both on the sales and operating profit, and also give us the idea of the contribution from the lack of depreciation to the margins from that business for the 9 months.

所以 2，請。首先回到山德士。我想知道您是否可以告訴我們口服固體業務在第 9 個月的銷售額和營業利潤的貢獻，並告訴我們沒有折舊對第 9 個月該業務的利潤率的貢獻個月。

Second bit on -- and linked to that is just when do you we think the disposal to Aurobindo will happen now? Is that going to be by the end of the year? Or should we continue to think this contributing to numbers in 2020?

第二點——與此相關的是，我們認為現在什麼時候會處置 Aurobindo？那是要到年底嗎？還是我們應該繼續認為這對 2020 年的數字有所貢獻？

And then second question, just on Sandostatin LAR. I noticed that you are not commenting about that in terms of an impact on generics. Just maybe you could give us some flavor of the impact that you're seeing in Europe, the proportion of the rest of world sales that are from Europe and what's happening ex Europe, what sort of growth are you seeing ex Europe that may be balancing any impact from the generics in Europe?

然後是第二個問題，關於 Sandostatin LAR。我注意到您沒有就對仿製藥的影響發表評論。也許你可以給我們一些關於你在歐洲看到的影響的味道，來自歐洲的世界其他地區銷售額的比例以及歐洲以外發生的事情，你看到歐洲以外的什麼樣的增長可能正在平衡歐洲的仿製藥有什麼影響嗎？

So Richard, on the Sandoz mix from oral solids versus biosimilars and other businesses.

所以理查德，在 Sandoz 混合口服固體與生物仿製藥和其他業務。

Thank you. Clearly, the Biologics business accounts for roughly, I guess, about 20% of the total business within Sandoz, give or take. And clearly, the biologics underlying growth is about 27%. So it's accelerating quickly versus, I guess, a still growing but flattish oral solids business. On your second part to that question, around Aurobindo clearly we are working closely with the authorities and with Aurobindo to close and hopefully we'll get that approved by the authorities within the next month or so.

謝謝。很明顯，我猜生物製品業務大約佔 Sandoz 總業務的 20%，或多或少。顯然，生物製劑的潛在增長約為 27%。所以它正在迅速加速，我猜，一個仍在增長但持平的口服固體業務。關於這個問題的第二部分，圍繞 Aurobindo，我們顯然正在與當局和 Aurobindo 密切合作以關閉，希望我們能在下個月左右獲得當局的批准。

And Harry, I think we also add a question on lack of depreciation. Any comment?

哈里，我想我們還添加了一個關於缺乏折舊的問題。任何意見？

Yes. That's a relatively small amount. We'll get back to you on that one. We have mentioned it before, but it's not very significant.

是的。這是一個相對較小的數額。我們會在那個問題上回复你。我們之前提到過它，但它不是很重要。

And then on Sandostatin [LAR sales], Susanne.

然後是 Sandostatin [LAR 銷售]，Susanne。

Sandostatin sales were broadly in line with last year. And when you put the different markets, there is still growth in the U.S. So the product's holding very well. While in Europe, we see some first erosion from generics. To give a little bit more color, so we know there is one generic company having marketing authorization for Europe, and they are now working through the local or national ratifications. We know that U.K., Spain, France, Switzerland and Germany have approvals. And we see first commercial activities in Germany, where we see first erosion of our product.

Sandostatin 的銷售額與去年基本持平。當你把不同的市場放在一起時，美國仍然有增長，所以該產品的銷量非常好。在歐洲，我們看到了仿製藥的初步侵蝕。為了提供更多顏色，我們知道有一家仿製藥公司獲得了歐洲的營銷授權，他們現在正在通過當地或國家的批准。我們知道英國、西班牙、法國、瑞士和德國已獲得批准。我們在德國看到了第一個商業活動，在那裡我們看到了我們產品的第一次侵蝕。

So going forward, you have to expect very focused erosion in some markets. That's what we expect. For the U.S., we have no news at this point. We continue to monitor the situation closely. But when you ask for how you would model that, we would expect there is only very limited generic entry, probably one company only, so we would see a more gradual erosion if a generic enters.

因此，展望未來，您必須預計某些市場會受到非常集中的侵蝕。這就是我們所期望的。對於美國，我們目前沒有消息。我們繼續密切關注局勢。但是當你問你將如何建模時，我們預計只有非常有限的仿製藥進入，可能只有一家公司，所以如果仿製藥進入，我們會看到更逐漸的侵蝕。

Thank you, Susanne, I just want to highlight this is a very complex manufacturing process. There is, as far as we know, only one potential generic entrant, depending on the market in Europe and the U.S. and not a product that's easy to supply in large volumes as well. So these are all important factors to consider when you think about Sandostatin LAR and the formulation.

謝謝你，Susanne，我只想強調這是一個非常複雜的製造過程。據我們所知，只有一個潛在的仿製藥進入者，這取決於歐洲和美國的市場，而不是一種容易大量供應的產品。因此，當您考慮 Sandostatin LAR 和配方時，這些都是需要考慮的重要因素。

And our next question comes from the line of Emmanuel Papadakis from Barclays.

我們的下一個問題來自巴克萊銀行的 Emmanuel Papadakis。

Maybe one on Aimovig, it seems to have had a somewhat slower start in Europe and it seems to be perhaps slowing somewhat in the U.S. So just your perspectives on market trajectory of development from here and if you're able to give us any update on litigation that will also be helpful. And the second should be relatively quick one, if you could give us any updates on the status of your pegfilgrastim filing in the U.S., that would also be helpful.

也許在 Aimovig 上有一個，它在歐洲的起步似乎有點慢，在美國似乎可能有所放緩所以請談談您對市場發展軌蹟的看法，如果您能向我們提供任何最新信息訴訟也將有所幫助。第二個應該相對較快，如果您能向我們提供有關您在美國的 pegfilgrastim 申請狀態的任何更新，那也會有所幫助。

So on Aimovig, Marie-France?

那麼關於 Aimovig，Marie-France？

So to answer your question on Europe, I mean where we've seen reimbursement, we've seen very strong uptake. If I take Germany as an example, we're doing extremely well in that market. Getting reimbursement in Europe has been difficult as we anticipated, given also the comparator to the product. In the U.S., actually, our performance is very good. We remain well differentiated. We've got 4.5-year data that confirm efficacy and the safety. We've got good access. And since we were first to market, it is a product that is familiar to physicians. We do expect Aimovig's performance to continue. And we will continue to pursue reimbursement outside of the U.S.

所以回答你關於歐洲的問題，我的意思是我們看到了報銷，我們看到了非常強勁的吸收。如果我以德國為例，我們在那個市場上做得非常好。正如我們預期的那樣，在歐洲獲得報銷一直很困難，還考慮到產品的比較。在美國，其實我們的表現非常好。我們保持良好的差異化。我們有 4.5 年的數據證實了療效和安全性。我們有很好的訪問權限。由於我們首先推向市場，因此它是醫生熟悉的產品。我們確實希望 Aimovig 的表現能夠繼續。我們將繼續在美國境外尋求報銷。

And on litigation, we have no material updates on the litigation. We'll of course keep everyone you up-to-date. On pegfilgrastim, Richard?

在訴訟方面，我們沒有關於訴訟的重大更新。我們當然會讓每個人都了解最新信息。在 pegfilgrastim 上，Richard？

Thank you Emmanuel. Clearly, we remain very confident in the quality of our dossier and we expect that the FDA should complete its review very soon.

謝謝伊曼紐爾。顯然，我們對檔案的質量仍然非常有信心，我們希望 FDA 盡快完成審查。

Next question coming from the line of Laura Sutcliffe.

下一個問題來自 Laura Sutcliffe。

Firstly, one on Zolgensma, please. You said that 2/3 of patients on Zolgensma -- incident patients on Zolgensma who have been given Zolgensma where newborn screening is being implemented. Do you have any sense of why it's at that level? Is that just a reflection of current Medicaid access? Or is there anything else at play there?

首先，請介紹 Zolgensma。你說 2/3 的 Zolgensma 患者——接受 Zolgensma 的 Zolgensma 事件患者正在實施新生兒篩查。你知道為什麼它在那個水平嗎？這是否只是當前 Medicaid 訪問的反映？或者那裡還有其他東西在玩嗎？

And then secondly, could you just remind us of your current situation with respect to a biosimilar etanercept at Sandoz? Any thoughts you have on a potential launch down the line there?

其次，您能否提醒我們您目前在 Sandoz 的生物仿製藥依那西普方面的情況？你對在那裡的潛在發射有什麼想法嗎？

So on Zolgensma, I think when there's newborn screening in place, we see, one, a high awareness of the potential of gene therapy to lead to a definitive, hopefully definitive, treatment for these patients. And so I think with gene therapy -- sorry, with newborn screening, there tends to be a high correlation with high degrees of awareness. When patients are identified later on, they tend not to be at specialized centers or we have to then work a little bit harder to get the switches to happen. So I think that's probably why we see that effect. Our aspiration is regardless of whether newborn screening or identified otherwise, we believe Zolgensma should be the first choice for all of those patients. And our aspiration is to be above 90% coverage of all of those early incident patients in SMA. With respect to etanercept, Richard?

所以在 Zolgensma 上，我認為當有新生兒篩查時，我們看到，一個，高度意識到基因治療的潛力，可以為這些患者帶來明確的，希望是明確的治療。所以我認為對於基因療法——抱歉，對於新生兒篩查，往往與高度的意識高度相關。當稍後確定患者時，他們往往不會在專門的中心，否則我們必須更加努力地工作才能實現轉換。所以我認為這可能就是我們看到這種效果的原因。我們的願望是，無論是否進行新生兒篩查或以其他方式確定，我們認為 Zolgensma 應該是所有這些患者的首選。我們的願望是 SMA 中所有早期發病患者的覆蓋率超過 90%。關於依那西普，理查德？

Again, thank you. So first nugget, clearly, Erelzi was approved by the FDA in 2016, but not launched due to the pending patent litigation with Amgen. The U.S. District Court of New Jersey ruled against us in the patent litigation on August 9. Now we respectfully disagree with the ruling. And while valid intellectual property should clearly be respected, we believe patient -- patents in this case are invalid. We've appealed already to the U.S. Court, Federal Circuit, and the parties have agreed to an expedited appeal. And we look forward to bringing Erelzi to U.S. patients as soon as possible. And clearly, we'll update you of any progress.

再次謝謝你。所以第一個金塊，顯然，Erelzi 在 2016 年獲得了 FDA 的批准，但由於與 Amgen 的未決專利訴訟而沒有推出。美國新澤西州地方法院於 8 月 9 日在專利訴訟中裁定我們敗訴。現在，我們謹表示不同意該裁定。雖然有效的知識產權顯然應該受到尊重，但我們相信患者——在這種情況下專利是無效的。我們已經向美國聯邦巡迴法院上訴，雙方同意加速上訴。我們期待盡快將 Erelzi 帶給美國患者。顯然，我們會向您通報任何進展。

And as soon as we have more color on when a potential decision might happen, we'll, of course, update all of you.

一旦我們有更多關於何時可能做出潛在決定的顏色，我們當然會更新你們所有人。

Next question is coming from the line of Seamus Fernandez for Guggenheim.

下一個問題來自古根海姆的 Seamus Fernandez。

So just a couple here. On fevipiprant I don't want to overread into the fevipiprant situation, but as I look at your slide deck, you specifically comment on a planned filing in 2020. And then in your appendix, it says that the LUSTER 2 trial is complete. Just a question here, do you have any data in hand from the LUSTER trials on exacerbation? Or is that review to be completed? It just seems like that there's an implication that in the eosinophil-high patient population, maybe there's an effect but you're waiting for LUSTER 1?

所以這裡只有一對。關於 fevipiprant，我不想過度解讀 fevipiprant 的情況，但當我看你的幻燈片時，你特別評論了 2020 年計劃提交的文件。然後在您的附錄中，它表示 LUSTER 2 試用已完成。這裡只是一個問題，你手頭有 LUSTER 加重試驗的數據嗎？還是要完成審查？這似乎暗示在嗜酸性粒細胞高的患者群體中，也許有效果，但您正在等待 LUSTER 1？

And then the second question, really, is to kind of focus in on the way that you see Beovu ramping. Maybe you could just help us understand the launch trajectory for Beovu and how we're going to see revenue kind of grow -- coming into the model. And maybe you can just metric that for us versus the kind of launch that we saw with Eylea.

然後第二個問題，真的，是有點關注你看到 Beovu 的方式。也許你可以幫助我們了解 Beovu 的發布軌跡，以及我們將如何看到收入增長——進入模型。也許你可以衡量一下我們在 Eylea 上看到的那種發布方式。

Yes. So on fevipiprant, first, it's important to note that in order to file in the severe population, we need both studies, the LUSTER 1 and the LUSTER 2 study. So in order for us to make a determination, we also need to see the pooled analysis across the 2 programs. We have locked -- as you rightly point out, we have locked the LUSTER 2 database. So we do have the initial readout from that study, but we're awaiting now the LUSTER 1 readout to understand where the overall program in the pooled analysis as well sits, all of the elements that would be required for a regulatory filing. We also have an additional study called the SPIRIT study, which is required from a safety standpoint as well. So once we have a clear perspective on all of these studies, we'll be able to provide an update in Q1. On Beovu, Marie-France?

是的。所以關於 fevipiprant，首先，重要的是要注意，為了在嚴重人群中歸檔，我們需要兩項研究，即 LUSTER 1 和 LUSTER 2 研究。因此，為了讓我們做出決定，我們還需要查看 2 個程序的匯總分析。我們已經鎖定——正如您正確指出的那樣，我們已經鎖定了 LUSTER 2 數據庫。因此，我們確實有該研究的初步讀數，但我們現在正在等待 LUSTER 1 讀數，以了解匯總分析中的整體計劃的位置，以及監管備案所需的所有要素。我們還有一項稱為 SPIRIT 研究的額外研究，從安全的角度來看，這也是必需的。因此，一旦我們對所有這些研究有了清晰的認識，我們將能夠在第一季度提供更新。在 Beovu，Marie-France？

Yes. So on Beovu, I will just really reiterate what we're hearing from the marketplace, which is that physicians are very excited to use the product. We know from clinical practice that fluid is the #1 factor for treatment and for switching decisions. We believe that Beovu will convince, given the HAWK and HARRIER data, and no doubt it will convince even more in clinical practice. We've seen a lot of positive feedback from AAO. I think what I would say is Beovu meets physician needs for greater fluid resolution in these patients' needs for greater treatment intervals. And we believe that Beovu will be a major player. I'll also say that I believe we've got a world-class team in place in the U.S. and that we'll see a really strong launch with Beovu.

是的。因此，在 Beovu 上，我將重申我們從市場上聽到的消息，即醫生對使用該產品感到非常興奮。我們從臨床實踐中知道，液體是治療和轉換決定的第一大因素。鑑於 HAWK 和 HARRIER 數據，我們相信 Beovu 將令人信服，而且毫無疑問它將在臨床實踐中更加令人信服。我們從 AAO 那裡看到了很多積極的反饋。我想我要說的是，Beovu 滿足了醫生對更大液體分辨率的需求，滿足了這些患者對更長治療間隔的需求。我們相信 Beovu 將成為主要參與者。我還要說的是，我相信我們在美國擁有一支世界級的團隊，我們將看到 Beovu 的強大發布。

The next question is coming from the line of Simon Baker from Redburn.

下一個問題來自 Redburn 的 Simon Baker。

Two, please. Firstly, on Zolgensma, I wonder if you could give us a little bit more color on the phrase "even distribution of patients by type and age." I'm assuming it's not dead 50-50. So any more color on there will be useful. And then sticking with fevipiprant I wonder if you could give any us thoughts on any potential mechanistic reason for the ZEAL result. Is this due to different implication of Th2 cells in moderate and severe asthma? There have been a few papers suggesting that maybe there could be some possible explanation there. So your thoughts on that will be much appreciated.

兩個，請。首先，關於 Zolgensma，我想知道你是否可以給我們更多關於“按類型和年齡均勻分佈患者”這一短語的顏色。我假設它沒有死 50-50。所以任何更多的顏色都會有用。然後堅持使用 fevipiprant 我想知道您是否可以就 ZEAL 結果的任何潛在機械原因給我們任何想法。這是由於 Th2 細胞在中度和重度哮喘中的不同含義嗎？有幾篇論文表明，也許那裡可能有一些可能的解釋。因此，您對此的想法將不勝感激。

Thanks, Simon. For Zolgensma, we're obviously not providing that granularity of detail, but what I can say is we've seen solid uptake in both patients between the ages of 1 and 2 and patients between the ages of 6 months and 1 year and patients below 6 months. So we've seen, I think, a relatively even distribution across these different age groups. And we've seen an even distribution as well between type 1, type 2 and type 3 patients. But those are the numbers -- those are the groups we're talking about when we say an even distribution. So I'd say, in large part, what we're trying to indicate is we are seeing approvals for the use of the medicine when prescribed when on label and after taking the appropriate steps with insurers.

謝謝，西蒙。對於 Zolgensma，我們顯然沒有提供那麼詳細的細節，但我可以說的是，我們已經看到 1 到 2 歲之間的患者和 6 個月到 1 歲之間的患者以及以下患者的穩定吸收6個月。所以我認為，我們已經看到這些不同年齡組的分佈相對均勻。我們也看到了 1 型、2 型和 3 型患者之間的均勻分佈。但這些就是數字——當我們說均勻分佈時，這些就是我們談論的群體。所以我要說的是，在很大程度上，我們試圖表明的是，我們正在看到在標籤上開處方並在與保險公司採取適當措施後使用該藥物的批准。

Now with respect to this ZEAL results and the mechanism, John?

現在關於這個 ZEAL 結果和機制，約翰？

Thanks for the question. I think you guys all know that fevipiprant is a selective DP2 agent. In that case, it's not a classic bronchodilator. What we know is that DP2 activation increases with disease. So in fact, as you have more disease, you actually would likely get more response from DP2s. Now just one correlation that you probably know in terms of the biologics or IL-5s, in the moderate population, there is not significant improvement in FEV1. So I think, in this respect, we obviously want to see the results of LUSTER 1 and 2 and expect to see better results in the DP2 antagonists for patients with severe population, especially with high eosinophils.

謝謝你的問題。我想你們都知道 fevipiprant 是一種選擇性 DP2 劑。在那種情況下，它不是經典的支氣管擴張劑。我們所知道的是，DP2 激活隨著疾病的增加而增加。所以事實上，當你有更多的疾病時，你實際上可能會從 DP2s 得到更多的反應。現在，就生物製劑或 IL-5 而言，您可能知道一種相關性，在中等人群中，FEV1 沒有顯著改善。所以我認為，在這方面，我們顯然希望看到 LUSTER 1 和 2 的結果，並期望在 DP2 拮抗劑中看到更好的結果，用於重度人群，尤其是高嗜酸性粒細胞患者。

Actually, Harry, you had one clarification.

事實上，Harry，你有一個澄清。

Just for Richard. Richard Vosser, you asked about the divested Sandoz U.S. business-related stock depreciation. It is a small number, is about $10 million per quarter. So $30 million year-to-date, $10 million per quarter is the stock depreciation.

只為理查德。Richard Vosser，你問到與剝離的 Sandoz 美國業務相關的股票貶值。這是一個很小的數字，大約每季度 1000 萬美元。所以年初至今 3000 萬美元，每季度 1000 萬美元是股票貶值。

The next question is coming from the line of Mark Purcell from Morgan Stanley.

下一個問題來自摩根士丹利的 Mark Purcell。

First, on China. Could you please help us understand the outlook for your business in China, framing the opportunities as well as the threats? Clearly very strong growth the more key growth drivers that you highlighted and launches to come as, in terms of Entresto and heart failure and consensus, et cetera. But from the threat perspective, obviously a number of LOEs I presume are coming up, potentially including products such as Galvus. So if you could help us understand the key approval decisions and your [L] decisions and LOE timings, that will be fantastic. There isn't a lot on LOE timings outside the U.S., Europe and Japan in your annual report.

首先，關於中國。您能否幫助我們了解貴公司在中國的業務前景、機遇和威脅？很明顯，非常強勁的增長是您強調和推出的更多關鍵增長驅動因素，如 Entresto 和心力衰竭以及共識等。但從威脅的角度來看，我認為顯然會出現一些 LOE，可能包括 Galvus 等產品。因此，如果您能幫助我們了解關鍵的批准決定以及您的 [L] 決定和 LOE 時間安排，那就太棒了。在你們的年度報告中，美國、歐洲和日本以外的 LOE 時間安排並不多。

And then secondly on canakinumab, I guess this a bit of a wildcard in your pipeline. Could you comment on the -- any interim analyses planned ahead of the primary completion of CANOPY 1 and 2 in the first half of 2021? And then just more broadly, in terms of your ambitions on IL-1 beta as a mechanism following the acquisition of the XOMA product.

然後是 canakinumab，我想這在您的管道中有點通配符。您能否評論 - 在 2021 年上半年初步完成 CANOPY 1 和 2 之前計劃的任何中期分析？然後更廣泛地說，就您在收購 XOMA 產品後將 IL-1 beta 作為一種機制的雄心壯志而言。

Thank you, Mark. On China broadly, we see it as, obviously, a very important opportunity for the company. We publicly stated we have overall business in IM that's over $2 billion. Our goal is to at least double that business over the 5-year term. It's driven entirely by new launches, our ability to launch new medicines. And I'll have John comment a bit more on the number of NRDL -- number of approvals and NDAs we expect and then maybe Marie-France can give more color on how we're doing on some of the launches. John?

謝謝你，馬克。從廣義上講，我們認為這對公司來說顯然是一個非常重要的機會。我們公開表示我們在 IM 方面的整體業務超過 20 億美元。我們的目標是在 5 年內將該業務至少翻一番。它完全由新的發布驅動，我們推出新藥的能力。我會讓 John 對 NRDL 的數量發表更多評論——我們期望的批准和 NDA 的數量，然後也許 Marie-France 可以就我們在某些發布上的表現給出更多的顏色。約翰？

Thanks Vas. As you know, we put a significant effort into China. Already in the last 2 years, we've had 24 NDAs approved. That's across 9 NMEs, new molecular entities. And moving forward over the next -- between now and 2023, we expect to have 50 NDA submissions. So in total, with that combination, it's over 70 NDAs. So a significant effort that we're putting in behind China over the last 2 years and over the next couple of years.

謝謝瓦斯。如您所知，我們在中國投入了大量精力。在過去的兩年裡，我們已經批准了 24 項新藥申請。這是跨越 9 個 NME，新的分子實體。在接下來的時間裡——從現在到 2023 年，我們預計將提交 50 份 NDA。因此，通過這種組合，總共有超過 70 個 NDA。因此，在過去兩年和接下來的幾年裡，我們在中國背後付出了巨大的努力。

And that fits with our overall belief with the 7 plus 4 initiative to take -- expand out of older medicines and free up resources to launch new medicines. We want to be well positioned with all of our portfolio available in China and ready to launch. Marie-France, do you want to give us some more color on how we're doing on some of those products?

這符合我們採取 7 加 4 倡議的總體信念——擴大舊藥並釋放資源以推出新藥。我們希望在中國擁有我們所有的產品組合併準備推出。Marie-France，你想給我們更多關於我們在其中一些產品上的表現的顏色嗎？

Yes. So first of all, I'll just comment and say that our China business is growing really well. Our growth rates are in the high 20s. The innovative portfolio is really what's driving the launch. So if we look at Entresto, Lucentis, Cosentyx, they're among the 5 growth drivers for China. Entresto is actually the best primary launch ever. And we do expect to see NRDL listing in Q4. So that should be a big opportunity for China. Cosentyx is also off to a great start, but obviously maintaining patients on an out-of-pocket setting is a challenge. So it is a priority for us to get NRDL listing also in 2020. We also expect NRDL listing for Lucentis and DME and RVO this year. So all in all, again, it's the innovative portfolio that's driving the growth. We currently have no products on the 4 plus 7 list, although that may change. And again, what we're going to focus on is really this innovative portfolio and expect to continue the strong growth.

是的。所以首先，我只想說我們的中國業務發展得非常好。我們的增長率在 20 多歲左右。創新的產品組合真正推動了發布。因此，如果我們看看 Entresto、Lucentis、Cosentyx，它們是中國的 5 大增長動力之一。Entresto 實際上是有史以來最好的主要發布。我們確實希望看到 NRDL 在第四季度上市。所以這對中國來說應該是一個巨大的機會。Cosentyx 也有一個良好的開端，但顯然讓患者保持自付費用是一項挑戰。因此，我們的當務之急是在 2020 年也將 NRDL 列入清單。我們還預計今年 Lucentis 和 DME 和 RVO 將列入 NRDL。因此，總而言之，推動增長的是創新產品組合。我們目前在 4 加 7 列表中沒有產品，儘管這可能會改變。再說一遍，我們真正要關注的是這個創新的產品組合，並期望繼續保持強勁增長。

On canakinumab, John, any interim expectations?

關於 canakinumab，John，有什麼臨時期望嗎？

Yes, so specifically, obviously, we had the PARAGON results readout. One of the areas that we're looking into is the post-acute...

是的，具體來說，很明顯，我們讀出了 PARAGON 結果。我們正在研究的領域之一是後急性...

No, no, sorry John, not Entresto, canakinumab, the non-small cell lung cancer, first line, second line.

不，不，對不起約翰，不是 Entresto，卡納單抗，非小細胞肺癌，一線，二線。

What we can say about canakinumab, sorry about the confusion there, for CANOPY trials, CANOPY 1 and 2, those are moving forward and recruiting well. We continue to see good results in terms of recruitment. Now what we do see in the adjuvant population is a little bit slower population in terms of recruitment in that study. But I think, balanced what you're seeing in the marketplace, there's just last patients that are actually moving forward in the adjuvant population. For CANOPY 1 and 2, those are moving forward very well in terms of recruitment. And CANOPY A in the adjuvant population is a bit slower than we expected.

關於 canakinumab，我們可以說些什麼，對那裡的混亂感到抱歉，對於 CANOPY 試驗，CANOPY 1 和 2，這些試驗正在向前推進並且招募良好。我們繼續在招聘方面看到良好的結果。現在，我們在佐劑人群中看到的是，在該研究中，就招募而言，人群有點慢。但我認為，平衡你在市場上看到的情況，只有最後一批患者在輔助人群中真正取得進展。對於 CANOPY 1 和 2，它們在招聘方面進展順利。而佐劑群體中的 CANOPY A 比我們預期的要慢一些。

So we do expect CANOPY-2 particularly, potentially CANOPY-1 to read out in 2021. I'd say more broadly, our efforts in IL-1 beta and the inflammasome are -- we are quite bullish on it. Not only did we have the canakinumab program, not only did we bring in a second agent for an IL-1 beta antibody but we've also acquired a company called IFM Tre, which has oral inflammasome inhibitors and we are now -- that molecule as well as an internal program we're taking across a range of autoimmune indications, oncology indications, neurological indications. So we would like to own the inflammasome space for the long term and that's what we are working towards.

因此，我們確實預計 CANOPY-2，特別是 CANOPY-1 可能會在 2021 年宣讀。我想更廣泛地說，我們在 IL-1 beta 和炎性體方面的努力是——我們非常看好它。我們不僅有 canakinumab 項目，不僅引入了 IL-1 β 抗體的第二種藥物，而且我們還收購了一家名為 IFM Tre 的公司，該公司擁有口服炎性體抑製劑，我們現在——那個分子以及我們正在進行的一項內部計劃，涉及一系列自身免疫適應症、腫瘤學適應症、神經系統適應症。因此，我們希望長期擁有炎症空間，這就是我們正在努力的方向。

Our next question comes from the line of Naresh Chouhan from Interim Health (sic) [Intrinsic Health].

我們的下一個問題來自 Interim Health (sic) [Intrinsic Health] 的 Naresh Chouhan。

Firstly, on Tasigna which seems to have returned to growth, at least in the U.S. Is it fair to assume that the impact from the TFR data is now played out and we should see sustained growth in the U.S.? And similarly so, in Europe in the coming quarters? And then secondly, the gross margin of Pharma was impacted by the cell and gene therapy investment. Should we expect that to continue well into 2020? Or is this a short-term impact given the Zolgensma uptake?

首先，Tasigna 似乎已經恢復增長，至少在美國是這樣。假設 TFR 數據的影響現在已經結束，我們應該看到美國的持續增長是否公平？同樣，未來幾個季度在歐洲？其次，製藥公司的毛利率受到細胞和基因治療投資的影響。我們是否應該期望這種情況會持續到 2020 年？還是考慮到 Zolgensma 的吸收，這是短期影響？

So I think both questions for Susanne. First on Tasigna, Susanne?

所以我認為這兩個問題都需要 Susanne。首先是 Tasigna，Susanne？

Yes, on Tasigna we saw indeed very strong growth of 11% in the quarter. So what we can say in the U.S., as you know, since a while we are focusing our messages around efficacy and around targeting new and switch patients. So we believe this strategy is paying off and we see the situation stabilize and expect modest growth going forward. The Q3 effect is an unusual one because it is artificially high because of inventory phasing versus Q3 in the U.S. So that I would not expect to go forward like that. But overall, we are pleased that Tasigna seems to be stabilized, and we'll expect modest growth going forward.

是的，在 Tasigna 上，我們在本季度確實看到了 11% 的非常強勁的增長。因此，正如您所知，我們在美國可以說的是，一段時間以來，我們一直將信息重點放在療效和針對新患者和轉換患者上。因此，我們相信這一戰略正在奏效，我們看到形勢趨於穩定，並預計未來將出現適度增長。第三季度的影響是不尋常的，因為與美國的第三季度相比，由於庫存階段而人為地高，所以我不希望像那樣前進。但總的來說，我們很高興 Tasigna 似乎已經穩定下來，我們預計未來會有適度增長。

And then cell and gene manufacturing investment?

然後是細胞和基因製造投資？

Yes. I say we have a lot of focus on improving our manufacturing process. And we are quite pleased that capacity has been gone up by 60% between Q1 and Q3, so making good progress there. We have started to ship out of (inaudible), which is the sign for cure side and sign for clinical supply and overall making good progress on that.

是的。我說我們非常注重改進我們的製造過程。我們很高興第一季度和第三季度的產能增加了 60%，因此取得了良好的進展。我們已經開始運出（聽不清），這是治愈方面的標誌和臨床供應的標誌，並且總體上在這方面取得了良好進展。

So I'd say our goal is to work back up. I think you were correct, we have with the cell and gene technology had to take some hit on our gross margins, particularly in oncology with CART therapy. Our aspiration is to now start to improve that and get that back up now in the coming year.

所以我想說我們的目標是恢復工作。我認為你是對的，我們的細胞和基因技術不得不對我們的毛利率造成一些影響，特別是在 CART 療法的腫瘤學方面。我們的願望是現在開始改進它，並在來年立即恢復它。

Last question I think, operator.

我想最後一個問題，運營商。

Our last question comes from Mani Foroohar from SVB Leerink.

我們的最後一個問題來自 SVB Leerink 的 Mani Foroohar。

I've got a quick first one on Zolgensma. Obviously, the expanded access and compassionate care dynamics in the U.S. are very different than other markets. When you think about the bolus phenomenon we're seeing in the U.S., could that phenomena actually be more pronounced in some other markets as you roll out in Japan, Europe, et cetera?

我在 Zolgensma 上有一個快速的第一個。顯然，美國擴大的可及性和富有同情心的護理動態與其他市場截然不同。當你想到我們在美國看到的推注現象時，當你在日本、歐洲等地推出時，這種現象實際上是否會在其他一些市場更加明顯？

And regarding sickle-cell for SEG101, it's a little different administration profile and reimbursement profile than the oral generic that's on the market currently but has really impressive clinical data. How do you think about investments in infrastructure and operational expertise that you can bring to bear to commercialize SEG101 across a market that has historically been pretty difficult to penetrate?

關於 SEG101 的鐮狀細胞，它的給藥方式和報銷方式與目前市場上的口服仿製藥略有不同，但臨床數據確實令人印象深刻。您如何看待基礎設施和運營專業知識的投資，您可以利用這些投資將 SEG101 商業化到一個歷史上很難滲透的市場？

Thanks for the questions, Mani. On Zolgensma ex U.S., what we have seen is in certain markets there is a high degree of interest. They've already put in access programs in place to enable use of the medicine in multiple patients. So I think in some countries in Europe as well in the Middle East, there could be very strong demand coming very quickly after approval. Difficult to dimensionalize precisely, given that obviously the rarity of the disease, but we do expect there to be similar, let's call it, pent-up demand effects in overseas markets. Now on SEG101, Susanne?

謝謝你的問題，瑪尼。在 Zolgensma ex U.S.，我們所看到的是在某些市場上有很高的興趣。他們已經實施了准入計劃，以便在多名患者中使用該藥物。因此，我認為在歐洲和中東的一些國家，批准後可能會很快出現非常強勁的需求。鑑於這種疾病顯然很罕見，很難精確衡量，但我們確實預計海外市場也會有類似的需求被壓抑的影響。現在在 SEG101 上，蘇珊娜？

Yes. We are quite diligently preparing for the launch of SEG101, looking forward to getting approval Q1 of next year. And when you ask about our commercial model, there's obviously big focus on access to get access approval very quickly. I'm very confident about the product because it has an impressive impact on patients. As you know, SEG101 is targeting VOCs, which is the hallmark of the disease. And when you talk to patients, how devastating pain crisis is and seeing that SEG101 could halve episodes of VOCs, I think that's impressive. That's also the feedback we get from physicians. So our focus is to work on access, but we're very confident and looking forward to being ready for launch.

是的。我們正在為SEG101的推出做相當認真的準備，期待明年Q1的批复。當您詢問我們的商業模式時，顯然非常關注訪問以非常快地獲得訪問批准。我對該產品非常有信心，因為它對患者產生了令人印象深刻的影響。如您所知，SEG101 以揮發性有機化合物為目標，這是該疾病的標誌。當您與患者交談時，疼痛危機是多麼具有破壞性，並且看到 SEG101 可以將 VOC 發作減半，我認為這令人印象深刻。這也是我們從醫生那裡得到的反饋。所以我們的重點是訪問，但我們非常有信心並期待著為發布做好準備。

Thank you, Susanne. So thank you all for joining today's call. We look forward to seeing you at our R&D day in early December. For those of you who can make it, we'll be focusing on profiling our next wave of innovation coming out of our early Phase III and late Phase II programs, so you'll get a sense of the next wave of important medicines we'll be bringing forward as a company as well as providing more detail on the depth of the programs we have on many of our products, including Cosentyx, Piqray and others that we've profiled over the course of today's call. Thank you for your interest in Novartis, and we'll look forward to speaking with you soon. Thank you.

謝謝你，蘇珊娜。感謝大家參加今天的電話會議。我們期待在 12 月初的研發日見到您。對於那些能夠成功的人，我們將專注於分析來自我們早期 III 期和晚期 II 期計劃的下一波創新浪潮，因此您將了解我們的下一波重要藥物。我們將作為一家公司提出建議，並提供更多關於我們在許多產品上的計劃深度的詳細信息，包括 Cosentyx、Piqray 和我們在今天的電話會議中介紹的其他產品。感謝您對諾華的關注，我們期待盡快與您交談。謝謝。

Thank you. That does conclude our conference for today. Thank you for participating. You may all disconnect.

謝謝。我們今天的會議到此結束。感謝您的參與。你們都可以斷開連接。