Novartis AG (NVS) 2022 Q3 法說會逐字稿

Good morning and good afternoon, and welcome to the Novartis Q3 2022 Results Release Conference Call and Live Webcast. (Operator Instructions) And the conference is being recorded. (Operator Instructions) A recording of the conference call, including the Q&A session, will be available on our website shortly after the call.

早上好，下午好，歡迎來到諾華 2022 年第三季度業績電話會議和網絡直播。 （操作員說明）會議正在錄製中。 （操作員說明）電話會議的錄音，包括問答環節，將在電話會議結束後不久在我們的網站上提供。

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

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

Thank you very much, and good morning and good afternoon, everybody. Thank you again for taking the time to participate in Novartis' quarter 3 conference call.

非常感謝大家，大家早上好，下午好。再次感謝您抽出寶貴時間參加諾華第三季度的電話會議。

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

在我們開始之前，只是快速提醒一下安全港。今天提供的信息包含涉及已知和未知風險、不確定性和其他因素的前瞻性陳述。這些可能導致實際結果與此類陳述所表達或暗示的任何未來結果、業績或成就存在重大差異。有關其中一些因素的描述，請參閱公司的 20-F 表格，該公司在表格 6-K 上的最新季度業績分別提交給美國證券交易委員會並提供給美國證券交易委員會。

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

有了這個，我將交給 Vas。

Thank you, Samir, and thanks, everyone, for joining on today's conference call.

謝謝你，薩米爾，謝謝大家參加今天的電話會議。

Moving to the first slide, we take a couple of slides forward. Novartis delivered solid quarter 3 performance really across all of our core value drivers. From a growth standpoint, group sales were up 4% in constant currencies. That was driven both by solid performance in IM at 4% as well as in Sandoz. U.S. IM sales were up 8%, consistent with our strategy to continue to improve our position in the U.S. market.

轉到第一張幻燈片，我們向前看幾張幻燈片。諾華在我們所有的核心價值驅動因素中都實現了穩健的第三季度業績。從增長的角度來看，集團銷售額按固定匯率計算增長了 4%。這得益於 4% 的 IM 和 Sandoz 的穩健表現。美國 IM 銷售額增長了 8%，這與我們繼續提高在美國市場地位的戰略一致。

From a productivity standpoint, group core operating income was up 5%, again driven by IM, which was up 7%. We also had continued our margin progression with a 1 percentage point improvement. Our savings from our SG&A program are on track, and Harry will cover that in a bit more detail.

從生產力的角度來看，集團核心營業收入增長了 5%，再次受到 IM 的推動，增長了 7%。我們還繼續提高利潤率，提高了 1 個百分點。我們從 SG&A 計劃中節省下來的資金正在按計劃進行，Harry 將更詳細地介紹這一點。

From an innovation standpoint, we had some important events, particularly the approval of Pluvicto with a positive opinion in Europe from the CHMP. And the readout we had and announced earlier this week of Iptacopan in PNH across 2 superiority endpoints versus anti-C5, and I'll go through that in a bit more detail.

從創新的角度來看，我們有一些重要的事件，特別是 Pluvicto 的批准以及 CHMP 在歐洲的積極評價。以及我們本週早些時候在 PNH 中獲得併宣布的 Iptacopan 在 2 個優勢終點與抗 C5 的讀數，我將更詳細地介紹這一點。

Lastly, on an ESG front, we had an important announcement with respect to our work with the Medicines Patent Pool as well as 2 -- additional important milestones for 2 development programs with hydroxyurea in sickle cell disease as well as in malaria.

最後，在 ESG 方面，我們發布了一項關於我們與藥品專利池以及 2 項合作的重要公告——另外兩個關於羥基脲在鐮狀細胞病和瘧疾中的開發項目的重要里程碑。

Moving to the next slide. The performance in the quarter was really driven by Entresto, Kesimpta, Kisqali and Pluvicto. And you can see the growth here for each of these brands. Entresto continues its strong trajectory. Kesimpta and Kisqali performing well. And Pluvicto in its first full quarter in the launch, also performing very well in its early days. We also saw good performance across some of the other brands, and we'll come to that brand by brand in the upcoming section.

轉到下一張幻燈片。本季度的業績真正受到 Entresto、Kesimpta、Kisqali 和 Pluvicto 的推動。您可以在這裡看到每個品牌的增長。 Entresto 繼續其強勁的發展軌跡。 Kesimpta 和 Kisqali 表現出色。而 Pluvicto 在其首個完整季度的發布中，在其早期表現也非常出色。我們還看到了其他一些品牌的良好表現，我們將在接下來的部分逐個品牌介紹該品牌。

Moving to Slide 6. One important element of our story is our ability to make our 6 key in-market growth drivers into multibillion-dollar medicines. And we stayed on track with respect to that, to really continue our confidence in our midterm growth outlook. Those 6 brands now account for 33% of IM sales, and they were growing 23% in the quarter. And as noted, both Scemblix and Pluvicto now are off to a good start and could one day be added to that list of 6 brands to also be potential multibillion dollar brands in the future, depending on how readouts go in the earlier lines.

轉到幻燈片 6。我們故事的一個重要元素是我們有能力將 6 個關鍵的市場增長驅動因素轉化為價值數十億美元的藥物。我們在這方面保持在正軌上，以真正繼續我們對中期增長前景的信心。這 6 個品牌現在佔 IM 銷售額的 33%，並且在本季度增長了 23%。如前所述，Scemblix 和 Pluvicto 現在都有一個良好的開端，有朝一日可能會被添加到這 6 個品牌的名單中，未來也可能成為價值數十億美元的品牌，這取決於早期產品線的讀數如何。

Moving to the next slide. Now we'll just take a walk through each of the individual brands, and I'll give you some of the key highlights from the quarter.

轉到下一張幻燈片。現在我們將瀏覽每個單獨的品牌，我將為您提供本季度的一些關鍵亮點。

Cosentyx showed steady growth in the quarter. You can see 7% growth in quarter 3. We were maintaining our competitive position in our 3 core geographies. We have over 875,000 patients now treated. In the U.S., we saw solid volume growth, but we also saw the impact of increased revenue deductions, particularly in Medicaid and 340B segments, relative to a previous uplift we saw in revenue deductions in the previous year. That's something we'll continue -- we expect to continue in quarter 4.

Cosentyx 在本季度呈現穩定增長。您可以在第三季度看到 7% 的增長。我們在三個核心地區保持了競爭地位。我們現在有超過 875,000 名患者接受治療。在美國，我們看到了穩健的銷量增長，但我們也看到了收入扣除增加的影響，特別是在醫療補助和 340B 領域，相對於我們在上一年的收入扣除中看到的先前提升。這是我們將繼續的事情——我們預計將在第 4 季度繼續。

Now with respect to Europe, we maintain our leadership position amongst originator biologics in psoriasis and spondyloarthritis.

現在，就歐洲而言，我們在銀屑病和脊柱關節炎的原始生物製劑中保持領先地位。

Future growth drivers for Cosentyx to get to that $7 billion peak sales will be driven by our continued expansion in China. Notably, in China, at the moment, we do face headwinds with the ongoing lockdowns, but we continue to expect China to be an important part of our story.

Cosentyx 達到 70 億美元峰值銷售額的未來增長動力將來自我們在中國的持續擴張。值得注意的是，目前在中國，我們確實面臨著持續封鎖的不利因素，但我們仍然希望中國成為我們故事的重要組成部分。

Hidradenitis suppurativa has now been filed -- submitted, filed in both FDA and EMA. I'll tell you a little bit more about why we feel like we have a good opportunity with this indication.

化膿性汗腺炎現已提交——提交，提交給 FDA 和 EMA。我會告訴你更多關於為什麼我們覺得我們有這個跡象的好機會。

We expect to submit our IV regulatory file in quarter 4. And we also continue to advance our life cycle management program across additional indications, including giant cell arteritis where we saw pretty solid Phase IIb data.

我們預計在第 4 季度提交我們的 IV 監管文件。我們還將繼續推進我們的生命週期管理計劃，涵蓋其他適應症，包括我們看到相當可靠的 IIb 期數據的鉅細胞動脈炎。

Now moving to Slide 8. Entresto continues strongly across all geographies, 31% growth in the quarter. You can see here the weekly TRx has continued to set record after record, really strong performance in the U.S., but also around the world. We now have over 8 million patients on therapy. Accelerating momentum in the U.S., strong demand in Europe.

現在轉到幻燈片 8。Entresto 在所有地區繼續強勁增長，本季度增長 31%。您可以在這裡看到每週的 TRx 繼續創下又一個記錄，在美國和世界各地的表現都非常強勁。我們現在有超過 800 萬患者正在接受治療。美國增長勢頭加快，歐洲需求強勁。

When you look at the future growth drivers of the brand, it's worth noting that only 1/3 of eligible HFrEF patients are currently on treatment in the G7. And there's a strong profile we continue to build in clinical and real real-world settings in heart failure. We have guidelines that continue to support the use of Entresto and HFrEF and also support its use in HFpEF. And we're also seeing good demand from the hypertension indications we were able to secure in Japan and in China.

當您查看該品牌的未來增長動力時，值得注意的是，目前只有 1/3 的符合條件的 HFrEF 患者正在接受 G7 治療。我們繼續在心力衰竭的臨床和真實世界環境中建立強大的形象。我們的指導方針繼續支持 Entresto 和 HFrEF 的使用，也支持其在 HFpEF 中的使用。我們還看到我們能夠在日本和中國獲得的高血壓適應症的良好需求。

Now moving to Slide 9. Zolgensma had a little bit of a challenged quarter. We now are predominantly seeing -- we're seeing demand from the incident population. Both U.S. and ex U.S. have shifted to an incident patient population. Year-to-date, we still have double-digit growth in incident patients treated, and we've exceeded 2,500 patients treated worldwide.

現在轉到幻燈片 9。 Zolgensma 有一點挑戰的季度。我們現在主要看到 - 我們看到事件人群的需求。美國和前美國都已轉移到事故患者群體。年初至今，我們治療的意外患者人數仍保持兩位數增長，我們在全球接受治療的患者已超過 2,500 人。

Going forward, what will be key for us is to continue to expand into new markets. It's a foundational treatment, as you all know, for Type 1 in newborns. We are approved in 45 countries, and we have access negotiations ongoing now in 10-plus markets, including some important markets, such as Brazil. We also continue to work to increase newborn screening rates to 35 -- above 35% in Europe and hopefully get over time to the rates that we see in the U.S., where we're close to 98% of newborn screened.

展望未來，我們的關鍵是繼續拓展新市場。眾所周知，這是針對新生兒 1 型的基礎治療。我們在 45 個國家/地區獲得批准，目前我們正在 10 多個市場進行准入談判，其中包括巴西等一些重要市場。我們還繼續努力將新生兒篩查率提高到 35 - 在歐洲超過 35%，並希望隨著時間的推移達到我們在美國看到的比率，在那裡我們接近 98% 的新生兒篩查率。

Taken together, we expect Zolgensma to -- we continue to expect Zolgensma to reach the $1.5 billion to $2 billion sales level in the IV indication alone. But getting beyond that sales level will require expansion into the intrathecal indication in the 2- to 18-year-old patient segment, where the STEER study is continuing to enroll, and we also have the STRENGTH study looking at the IV utilization in that indication starting in Q4 2022.

總而言之，我們預計 Zolgensma 將——我們繼續預計 Zolgensma 僅在 IV 適應症中就達到 15 億至 20 億美元的銷售額水平。但是，要超越這個銷售水平，就需要擴大到 2 至 18 歲患者群體的鞘內適應症，STEER 研究仍在繼續招募，我們也有 STRENGTH 研究著眼於該適應症中的 IV 利用率從 2022 年第四季度開始。

Now moving to Slide 10. Kisqali had a really strong quarter across all regions, with 49% growth on the quarter. You can see, importantly, in the middle panel of the slide, the trend break we've had with respect to NBRx share in the U.S. in the metastatic population, where we've been able to climb over the course of this year from 12% to 13% to now 26% exiting in August. That's really on the back of the strong data that we have with respect to OS across all of the metastatic lines. It's the only CDK4/6 with overall survival benefit across 3 Phase III studies. We also have a strong data with respect to quality of life.

現在轉到幻燈片 10。 Kisqali 在所有地區都有一個非常強勁的季度，本季度增長了 49%。重要的是，您可以在幻燈片的中間面板中看到我們在 NBRx 在美國轉移性人群中所佔份額的趨勢突破，我們在今年的過程中已經能夠從 12 % 到 13% 到現在 26% 在 8 月退出。這實際上是基於我們在所有轉移線上擁有的關於操作系統的強大數據的支持。它是唯一一個在 3 項 III 期研究中具有總體生存獲益的 CDK4/6。我們還擁有關於生活質量的強大數據。

We've launched a head-to-head study, the HARMONIA study versus Ibrance to further solidify that profile. And the NATALEE study continues. We have not had any feedback yet from the steering committee with respect to the first interim analysis. And when that feedback becomes available, if it indicates any action on our part, we'll, of course, inform the market.

我們發起了一項面對面的研究，即 HARMONIA 研究與 Ibrance 的對比，以進一步鞏固這一形象。 NATALEE 研究仍在繼續。我們尚未收到指導委員會對第一次中期分析的任何反饋。當該反饋可用時，如果它表明我們採取了任何行動，我們當然會通知市場。

Moving to Slide 11. Now Kesimpta had strong sales growth as well in the quarter, driven by its U.S. launch momentum, 172% you can see here on its launch trajectory. Really, all of the key metrics are trending in a favorable direction. TRx, 131%. NBRx, 47% versus a market notably that's declining 20%. We are up to 30% NBRx share in B-cell -- amongst B-cell therapies in MS in the U.S. with a goal to reach 50% share. We're adding 100 new writers per month. Our initiation programs with our patient hub are performing extremely well.

轉到幻燈片 11。現在 Kesimpta 在本季度也有強勁的銷售增長，這得益於其在美國的發布勢頭，您可以在此處看到其發布軌蹟的 172%。確實，所有關鍵指標都朝著有利的方向發展。 TRx，131%。 NBRx 為 47%，而市場明顯下降了 20%。我們在 B 細胞中的 NBRx 份額高達 30%——在美國 MS 的 B 細胞療法中，我們的目標是達到 50% 的份額。我們每月增加 100 位新作家。我們與患者中心的啟動計劃表現非常好。

And we also released new 4-year data in recently diagnosed and treatment-naive Kesimpta patients that support its use in earlier stages in RMS disease. So really good trajectory here and an opportunity for us now to also accelerate our efforts outside of the United States to bring this medicine to more multiple sclerosis patients around the world.

我們還發布了最近診斷和未經治療的 Kesimpta 患者的新 4 年數據，支持其在 RMS 疾病早期階段的使用。因此，這裡的發展軌跡非常好，我們現在有機會加快我們在美國以外的努力，將這種藥物帶給世界各地更多的多發性硬化症患者。

Now moving to the next slide. Now with Leqvio, as we've noted, this is a steady build over the course of 2023 and the first half of 2024. Last quarter, we highlighted that we have good data or good positioning right now with respect to market access with 70% of lives covered at or near the full label. The vast majority of patients are able to access the medicine with a low co-pay. And now what we're doing is step-by-step expanding HCP adoption with now 4,800 or so physicians that have been able to initiate a patient on Leqvio. What is critical now for us is to guide these physicians through the process so that they're able to get their patients on board, they're able to see how buy and bill work. And importantly, they're also able to see the impact of the medicine on lowering LDL for their patients.

現在轉到下一張幻燈片。正如我們所指出的，現在有了 Leqvio，這是 2023 年和 2024 年上半年的穩定增長。上個季度，我們強調我們目前在市場准入方面擁有良好的數據或良好的定位，佔 70%在完整標籤處或附近覆蓋的生命。絕大多數患者能夠以較低的共付額獲得藥物。現在我們正在做的是逐步擴大 HCP 的採用，現在有 4,800 名左右的醫生能夠在 Leqvio 上啟動患者。現在對我們來說至關重要的是指導這些醫生完成整個過程，以便他們能夠讓他們的患者參與進來，他們能夠了解購買和計費的工作方式。重要的是，他們還能夠看到藥物對降低患者低密度脂蛋白的影響。

What we find is in physicians that have gone through that process and have ultimately seen the impact on their patients, over 80% of patient -- physicians are pleased by the process and are pleased by the clinical and safety profile of the medicine. We just need to get more physicians through that process. So you can see some of the other data on the right-hand side. We have a free trial offer as well that's launched has seen strong uptake.

我們發現，在經歷過這一過程並最終看到對患者的影響的醫生中，超過 80% 的患者——醫生對這一過程感到滿意，並對藥物的臨床和安全狀況感到滿意。我們只需要讓更多的醫生通過這個過程。因此，您可以在右側看到一些其他數據。我們還提供免費試用優惠，該優惠已推出並受到強烈歡迎。

So we'll continue to work through the hurdle step-by-step. I think the right things are happening. But again, this is going to take time. And we really think it's midyear next year before you would expect to see any further acceleration beyond the linear path that we're on at the moment.

因此，我們將繼續逐步克服障礙。我認為正確的事情正在發生。但同樣，這需要時間。我們真的認為在明年年中之前，你會期望看到我們目前所走的線性路徑之外的任何進一步加速。

Now moving to the next slide. Pluvicto, as I noted in my opening comments, is off to a strong start in the U.S. We're seeing very rapid launch uptake for this brand in the third, fourth line castrate-resistant prostate cancer, metastatic prostate cancer segment. $80 million in share, we're already up to 14% NBRx share in the post-taxane setting. We have 120 centers actively ordering, and we're really focused on servicing those centers in an outstanding way. 75% of insured lives are covered, and we have a permanent A code now in effect as of October.

現在轉到下一張幻燈片。正如我在開場評論中指出的那樣，Pluvicto 在美國的開局強勁。我們看到該品牌在第三、四線去勢抵抗性前列腺癌、轉移性前列腺癌領域的推出速度非常快。 8000 萬美元的份額，我們在紫杉烷後的環境中已經擁有高達 14% 的 NBRx 份額。我們有 120 個中心正在積極訂購，我們真正專注於以出色的方式為這些中心提供服務。 75% 的被保險人都得到保障，我們的永久 A 代碼自 10 月起生效。

Now looking ahead, as we prepare for additional data and potential expansion of the indications for this medicine, we're expanding the number of treatment centers. We expect to, over time, get to 350 to 400 centers. We're significantly increasing our manufacturing capacity. And we have our Italian site at Ivrea online and Millburn and Indianapolis are planned for 2023.

現在展望未來，隨著我們準備更多數據和該藥物適應症的潛在擴展，我們正在擴大治療中心的數量。隨著時間的推移，我們預計將達到 350 到 400 個中心。我們正在顯著提高我們的製造能力。我們在 Ivrea 有我們的意大利網站在線，米爾本和印第安納波利斯計劃在 2023 年推出。

I mentioned already the positive CHMP opinion, and we're on track for the readout of PSMAfore before the end of this year and PSMAddition. And of note, PSMAfore, our current assessment is this would cover all pre-taxane metastatic patients, eliminating the need for one of the additional studies we had previously expected to be running in that setting. And in PSMAddition, in the hormone sensitive setting, we would expect to read out in 2024. So more to come, but overall, a solid launch so far with Pluvicto.

我已經提到了 CHMP 的積極意見，我們有望在今年年底之前公佈 PSMAfore 和 PSMAddition。值得注意的是，PSMAfore，我們目前的評估是這將涵蓋所有紫杉烷前轉移患者，從而無需我們之前預計在該環境中進行的一項額外研究。在 PSMAddition 中，在激素敏感的環境中，我們預計將在 2024 年讀出。所以會有更多，但總的來說，到目前為止，Pluvicto 的推出是可靠的。

Now moving to the next slide, looking at Scemblix. Scemblix, also continuing a solid launch momentum through quarter 3. You can see $41 million in sales, 13% total overall patient share in the third-line setting and 39% third line new patient share. That new patient share growth has slowed a bit, as we would have expected, as we need patients to switch off of therapies that they're currently in line to be typically moved to Scemblix.

現在轉到下一張幻燈片，查看 Scemblix。 Scemblix 也在第三季度繼續保持強勁的發布勢頭。您可以看到 4100 萬美元的銷售額，13% 的三線患者總患者份額和 39% 的三線新患者份額。正如我們所預料的那樣，新患者份額的增長有所放緩，因為我們需要患者關閉他們目前排隊的治療方法，以便通常轉移到 Scemblix。

Looking ahead, we've had the accelerated approval converted to a regular approval based on 96-week data. The global rollout is ongoing. And importantly, our Phase III study is enrolling ahead of plan. Right now, we forecast the readout expected on this first...

展望未來，我們已根據 96 週的數據將加速審批轉換為常規審批。全球推廣正在進行中。重要的是，我們的 III 期研究提前入組。現在，我們首先預測預期的讀數……

(technical difficulty)

（技術難度）

Thank you for your patience. Please continue to standby, your conference will begin shortly.

感謝您的耐心等待。請繼續待機，您的會議即將開始。

Hi, operator, this is Vas, we're back.

嗨，接線員，我是 Vas，我們回來了。

Thank you, sir. You are live.

謝謝你，先生。你是活的。

I think we were trying to (inaudible)

我想我們試圖（聽不清）

So I think I'll just step back, operator, to one slide previously. So when I talk about moving to (inaudible) Scemblix, which would be on Slide 14. We continue to see strong launch momentum where we have Q3 sales driven in part by -- Q3 sales were $41 million, and we had a 13% patient share in the third-line setting. NBRx is at 39%. And overall, we expect Scemblix, the critical element now, will be moving forward our ability to move into the earlier line. The study is enrolling ahead of plan, and we'll provide further updates. But right now, we forecast the second half 2024 outlook for Scemblix.

因此，我想我會退後一步，操作員，回到之前的一張幻燈片。因此，當我談到轉移到（聽不清）Scemblix 時，這將在幻燈片 14 上。我們繼續看到強勁的發布勢頭，我們第三季度的銷售額部分是由第三季度的銷售額為 4100 萬美元推動的，我們有 13% 的患者分享三線設置。 NBRx 為 39%。總體而言，我們預計現在的關鍵要素 Scemblix 將推動我們進入早期生產線的能力。該研究正在提前註冊，我們將提供進一步的更新。但現在，我們預測 Scemblix 2024 年下半年的前景。

Now turning to some of the clinical data we had in the quarter. Cosentyx, we had previously top line data, 16-week data in hidradenitis suppurativa. Now we have the 52-week data in-house. And just to remind everyone that it's a high unmet need patient population, one of the more common dermatological conditions that dermatologists see. 95% of eligible patients are not on a biologic today and 50% of biologic-treated patients lose the response over time. So there's definitely a need for a better therapy that can sustain its efficacy over time.

現在轉向我們在本季度獲得的一些臨床數據。 Cosentyx，我們之前有一線數據，化膿性汗腺炎的 16 週數據。現在我們擁有內部 52 週的數據。並且只是提醒大家，這是一個高度未滿足的患者群體，這是皮膚科醫生看到的更常見的皮膚病之一。 95% 的符合條件的患者今天沒有使用生物製劑，50% 的接受生物製劑治療的患者隨著時間的推移失去反應。因此，肯定需要一種更好的療法，可以隨著時間的推移維持其療效。

With the SUNSHINE and SUNRISE data set, we were able to collect data both at the 16-week and 52-week time period. We've already demonstrated data that showed a rapid relief from pain flares and lesion, but now we have data in-house to suggest that we have a unique benefit to sustain the response over 52 weeks, along with a favorable safety profile. So we look forward to sharing that data. We have filed, as I mentioned already, with the regulators. And overall, we're hopeful that this can be a key growth driver for Cosentyx over the coming years.

使用 SUNSHINE 和 SUNRISE 數據集，我們能夠收集 16 周和 52 週時間段的數據。我們已經展示了顯示疼痛發作和損傷迅速緩解的數據，但現在我們有內部數據表明我們有一個獨特的好處來維持超過 52 週的反應，以及良好的安全性。因此，我們期待分享這些數據。正如我已經提到的，我們已經向監管機構提交了申請。總體而言，我們希望這可以成為 Cosentyx 在未來幾年的主要增長動力。

Now moving to the next slide. Earlier this week, we announced the release of the Iptacopan Phase III data in PNH, and this is a medicine we believe can become a pipeline in a pill over time with the range of indications we're currently developing the medicine for. As a reminder, we are in -- we read out the PNH Phase III with an additional Phase III upcoming, the APPOINT-PNH study. We're in Phase III studies in IgAN, C3G and atypical hemolytic uremic syndrome. And we have a range of additional indications currently ongoing.

現在轉到下一張幻燈片。本週早些時候，我們宣佈在 PNH 中發布 Iptacopan III 期數據，我們認為隨著時間的推移，隨著我們目前正在開發該藥物的適應症範圍，這種藥物可以成為藥丸中的一種藥物。提醒一下，我們正在 - 我們宣讀了 PNH 第三階段以及即將到來的第三階段，即 APPOINT-PNH 研究。我們正在進行 IgAN、C3G 和非典型溶血性尿毒症綜合徵的 III 期研究。我們目前還有一系列額外的跡象。

As a reminder, the APPLY-PNH study related to the treatment of patients who had refractory anemia after treatment with an anti-C5 and the APPOINT study is in treatment-naive patients to anti-C5 antibodies, also expected to read out in 2022.

提醒一下，APPLY-PNH 研究與抗 C5 治療後難治性貧血患者的治療有關，而 APPOINT 研究是針對未接受抗 C5 抗體治療的患者，預計也將在 2022 年公佈。

Now looking on the next slide, Slide 17, to the APPLY-PNH study specifically. This is a study, as I mentioned, patients were on C5 therapy for up to 8 weeks. They then switched to -- if they had refractory anemia that demonstrated hemoglobin levels of less than 10 grams per deciliter, they were randomized to either receive Iptacopan or an anti-C5 therapy for 24 weeks. And after that period of time, they would continue on Iptacopan for the extension period. We demonstrated superiority for both endpoints, and I would say clinically meaningful superiority on both endpoints in terms of proportion of patients at greater than 2 grams and greater than 12 grams per dl.

現在看下一張幻燈片，幻燈片 17，專門針對 APPLY-PNH 研究。正如我所提到的，這是一項研究，患者接受 C5 治療長達 8 週。然後他們改用——如果他們患有頑固性貧血，顯示血紅蛋白水平低於每分升 10 克，他們被隨機分配接受 Iptacopan 或抗 C5 治療 24 週。在那段時間之後，他們將在延長期內繼續使用 Iptacopan。我們證明了這兩個終點的優勢，我會說這兩個終點的臨床意義優勢在於大於 2 克和大於 12 克/dl 的患者比例。

We have submitted this data or plan to submit this data to an upcoming medical congress, where we would share not only the magnitude of the effect in the primary endpoint, but also secondary endpoints, which cover -- secondary endpoints, including transfusion independence, quality of life, overall response rate as well as other measures.

我們已經提交了這些數據或計劃將這些數據提交給即將召開的醫學大會，屆時我們不僅會分享主要終點的影響程度，還會分享次要終點，包括次要終點，包括輸血獨立性、質量生命、總體反應率以及其他措施。

So moving to the next slide. Just as a reminder, our goal with this medicine is to be a first-line therapy for all patients with PNH. And that is the positioning that we plan to achieve both through our labeling and through the launch process. 10 to 20 cases per million is the current estimate of PNH with a current prevalence in the United States of 4,000 to 6,000. In the population of the current study that we just read out, about 40% of patients remain anemic with hemoglobin less than 10 grams per deciliter on anti-C5 therapies.

所以轉到下一張幻燈片。提醒一下，我們使用這種藥物的目標是成為所有 PNH 患者的一線治療。這就是我們計劃通過標籤和發布過程實現的定位。目前估計每百萬人中有 10 至 20 例 PNH，目前在美國的患病率為 4,000 至 6,000。在我們剛剛宣讀的當前研究人群中，大約 40% 的患者在接受抗 C5 治療時仍然存在貧血，血紅蛋白低於 10 克/分升。

It's also worth noting that a higher proportion of patients have some level of anemia, some level of fatigue or other clinical manifestations of the disease. So the unmet need is significant even in the case of anti-C5 treatments. And 50% of patients -- of these patients receive transfusions. We believe Iptacopan presents a unique opportunity to address both intra and extravascular hemolysis, potential for lower transfusion requirements and improvements in the quality of life. We think the oral administration in this setting makes a lot of sense, and then we can talk more about that in the Q&A. And we believe that this -- there is a potential for this medicine to have a broad first-line label.

還值得注意的是，較高比例的患者有某種程度的貧血、某種程度的疲勞或該疾病的其他臨床表現。因此，即使在抗 C5 治療的情況下，未滿足的需求也很重要。 50% 的患者——這些患者中接受了輸血。我們相信 Iptacopan 提供了一個獨特的機會來解決血管內和血管外溶血、降低輸血需求和改善生活質量的潛力。我們認為這種情況下的口服給藥很有意義，然後我們可以在問答中討論更多。我們相信，這種藥物有可能擁有廣泛的一線標籤。

Moving to the next slide. Lastly, before handing it over to Harry, Sandoz has delivered another solid quarter of growth. And you can see the growth rates here where we once again had a 4% sales growth. This was driven in part by Europe, but particularly by our performance in the rest of world markets, where we had double-digit growth. This is the fourth consecutive quarter of solid top line growth for Sandoz despite having to overcome the impact of Russia and Ukraine and absorbing inflation and other headwinds. We've revised the full year guidance upwards, and Harry will speak more about that.

轉到下一張幻燈片。最後，在將其移交給 Harry 之前，Sandoz 實現了又一個穩健的季度增長。您可以在這裡看到我們再次實現 4% 的銷售額增長的增長率。這部分是由歐洲推動的，尤其是我們在世界其他市場的表現，我們在這些市場實現了兩位數的增長。這是山德士連續第四個季度實現穩健的收入增長，儘管必須克服俄羅斯和烏克蘭的影響並吸收通貨膨脹和其他不利因素。我們已經向上修訂了全年指導，Harry 將對此進行更多討論。

And we want to just remind again that biosimilars are the key future growth driver of the business. We had the file acceptance of adalimumab high concentration and natalizumab in the quarter as well as a positive Phase III result for denosumab as well from the biosimilars unit. So with that, I will -- and we're on track, I should say, as well for the spin -- planned spin in the second half of next year.

我們想再次提醒一下，生物仿製藥是該業務未來的關鍵增長動力。我們在本季度獲得了高濃度阿達木單抗和那他珠單抗的文件接受，以及來自生物仿製藥部門的狄諾塞麥的積極 III 期結果。因此，我將 - 我應該說，我們正在按計劃進行旋轉，計劃在明年下半年進行旋轉。

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

所以有了這個，我會把它交給哈利。

Yes. Thank you, Vas. Good morning, good afternoon, everyone. I'm now going to walk you through some of the financials for the third quarter and the first 9 months of the year. And as always, my comments refer to growth rates in constant currencies. This is, of course, particularly important given the significant currency fluctuations we all see, and so we believe it offers a better view of the underlying operational performance.

是的。謝謝你，瓦斯。大家早上好，下午好。我現在將向您介紹第三季度和今年前 9 個月的一些財務狀況。和往常一樣，我的評論指的是固定貨幣的增長率。當然，鑑於我們都看到的重大貨幣波動，這一點尤其重要，因此我們相信它可以更好地了解潛在的運營績效。

On Slide 21, this shows the usual summary of our operational performance for the third quarter and the first 9 months. We have also provided growth rates with and without the impact of the prior year Roche income to allow a better understanding of the underlying business. As you can see, we maintained our growth momentum in the quarter, with quarter 3 sales growing plus 4% and core operating income plus 5%, with sales growth driven by our major Innovative Medicines brands, in particular Entresto, Kesimpta and Kisqali. Higher sales were also reflected in higher core operating income growth and inflationary headwinds have been offset by productivity efforts.

在幻燈片 21 上，這顯示了我們第三季度和前 9 個月的運營業績的常規摘要。我們還提供了有和沒有上一年羅氏收入影響的增長率，以便更好地了解基礎業務。如您所見，我們在本季度保持了增長勢頭，第三季度銷售額增長了 4%，核心營業收入增長了 5%，銷售額增長由我們的主要創新藥物品牌推動，特別是 Entresto、Kesimpta 和 Kisqali。更高的銷售額也反映在更高的核心營業收入增長中，而通貨膨脹的不利因素已被生產力努力所抵消。

Operating and net income declined in the quarter, mainly due to higher impairments of about $0.5 billion and higher restructuring costs of about $0.4 billion versus prior year, which were mainly due to the implementation of our previously announced streamlined organizational model. Core EPS grew 1%. However, if you exclude the impact of the prior year Roche income, core EPS would have grown 10%. Free cash flow in the quarter was strong with $4.2 billion, but declined 6% in U.S. dollars versus prior year with a significant impact from currencies.

本季度營業收入和淨收入下降，主要是由於減值增加約 5 億美元，重組成本較上年增加約 4 億美元，這主要是由於實施了我們先前宣布的精簡組織模式。核心每股收益增長 1%。但是，如果排除上一年羅氏收入的影響，核心每股收益將增長 10%。本季度的自由現金流強勁，達到 42 億美元，但以美元計較上年下降 6%，主要受匯率影響。

Turning to the first 9 months. We delivered a stronger -- a slightly stronger growth year-to-date, with sales growing 5% and core operating income growing 6%. Core EPS in the first 9 months grew 11%, excluding the Roche stake impact.

回到前 9 個月。今年迄今為止，我們實現了更強勁的增長，銷售額增長了 5%，核心營業收入增長了 6%。前 9 個月的核心每股收益增長了 11%，不包括羅氏股份的影響。

On the next slide, I would like to drill down, as usual, into the performance by division. So for Q3, Innovative Medicines top line grew 4%, and the bottom line, 7%, resulting in an improvement of the core margin of 100 basis points to 38.1%. Sandoz net sales also grew 4%, although core operating income decreased 5%, mainly due to increased M&S investments versus a quite low prior year base and prior year small divestment gains. This was reflected in the core margin, which decreased to approximately 22% of sales, which is also in line with the year-to-date core margin for Sandoz.

在下一張幻燈片上，我想像往常一樣深入了解按部門劃分的表現。因此，對於第三季度，創新藥物的收入增長 4%，利潤增長 7%，導致核心利潤率提高 100 個基點至 38.1%。山德士的淨銷售額也增長了 4%，儘管核心營業收入下降了 5%，這主要是由於 M&S 投資增加，而去年基數很低，而且去年的撤資收益很小。這反映在核心利潤率上，佔銷售額的比例下降到約 22%，這也與山德士年初至今的核心利潤率一致。

Overall, for the first 9 months, we saw a slightly stronger sales performance for both divisions. IM sales grew 5% and core operating income, 6%. And for Sandoz, sales grew 6% and 5% on the bottom line, benefiting from a strong cough and cold season, return towards normal business dynamics and a low prior year base in the first half of the year. Our year-to-date core margin improved by 50 basis points for IM, which drove then also the 50 basis points improvement for the group.

總體而言，在前 9 個月，我們看到這兩個部門的銷售業績略強。 IM 銷售額增長 5%，核心營業收入增長 6%。對於山德士來說，銷售額增長了 6% 和 5%，這得益於強勁的咳嗽和感冒季節，恢復了正常的業務動態以及上半年的低上年基數。我們年初至今的 IM 核心利潤率提高了 50 個基點，這也推動了集團的 50 個基點的提高。

Now on to Slide 23. On the next slide, a reminder of the cost impacts of our simplified organizational model. We continue to expect to deliver USD 1.5 billion in structural cost savings to be fully embedded by 2024. And as a reminder, we also expect onetime restructuring costs to be 1 to 1.2x this annual structural savings. And for year-to-date this year, we have around $0.8 billion in restructuring costs related to the new streamlined model and expect approximately a total of $1 billion for the full year of restructuring costs on this topic. The rest of the onetime restructuring costs we anticipate will largely fall into 2023.

現在轉到幻燈片 23。在下一張幻燈片上，提醒我們簡化組織模型的成本影響。我們繼續預計到 2024 年將完全實現 15 億美元的結構性成本節約。提醒一下，我們還預計一次性重組成本將是每年結構性節約成本的 1 到 1.2 倍。今年迄今為止，我們有大約 8 億美元與新的精簡模型相關的重組成本，預計全年在這一主題上的重組成本總計約為 10 億美元。我們預計其餘的一次性重組成本將在很大程度上落入 2023 年。

This year, we do expect to see some savings. As you can see here illustrative on the chart. But the overall impact will be minimal as this will offset higher energy cost inflationary pressures. All of these elements are, of course, part of our 2022 guidance. As a reminder, part of the $1.5 billion savings we expect to be reinvested into our pipeline and a significant part will contribute to achieve our approximately 40% plus margin target in the 2027 plus time frame.

今年，我們確實希望看到一些節省。正如您在圖表上看到的那樣。但整體影響將微乎其微，因為這將抵消更高的能源成本通脹壓力。當然，所有這些元素都是我們 2022 年指導方針的一部分。提醒一下，我們預計節省的 15 億美元中的一部分將重新投資到我們的管道中，其中很大一部分將有助於實現我們在 2027 年以上的時間框架內實現約 40% 以上的利潤率目標。

Now turning to Page 24. Within the divisions, we expect Innovative Medicine sales growing mid-single digit and core operating income growing mid- to high single digits ahead of sales. The anticipated Innovative Medicines' core margin increase should be driven by the expected continued good top line momentum and the continuation of our productivity programs, including the new streamlined organization model.

現在轉到第 24 頁。在各部門內，我們預計創新藥物銷售額將增長中個位數，核心營業收入將在銷售額之前增長中高個位數。預期創新藥物的核心利潤增長應該受到預期持續良好的頂線勢頭和我們生產力計劃的延續（包括新的精簡組織模式）的推動。

For Sandoz, the performance year-to-date allows us to upgrade sales and core operating income guidance, and sales are now expected to grow low to mid-single digit, revised upward from low single digit. And core operating income is now expected to grow low single digit, revised upward from broadly in line.

對於山德士來說，年初至今的業績使我們能夠上調銷售和核心營業收入指導，現在預計銷售額將從低個位數向上修正至低個位數至中個位數。現在預計核心營業收入將增長低個位數，從大致一致向上修正。

For the group, we confirm our overall guidance. We continue to expect both top and bottom line to grow mid-single digit in 2022. And as you have seen from our year-to-date results, we are quite on track -- very much on track to deliver on that guidance. The key assumption for this guidance is that we see continuing return to normal global prescribing behavior and health care systems and that no Sandostatin LAR generics would enter in the U.S. in 2022. The guidance also takes into account the entry of Gilenya generics that have now launched in the U.S. For your information, Gilenya U.S. sales in quarter 3 were $326 million.

對於該小組，我們確認了我們的總體指導。我們繼續預計 2022 年的收入和利潤都將增長中個位數。正如你從我們年初至今的業績中看到的那樣，我們已經步入正軌——非常有望實現這一指導。該指南的關鍵假設是，我們看到全球處方行為和醫療保健系統將繼續恢復正常，並且 Sandostatin LAR 仿製藥將在 2022 年進入美國。該指南還考慮了現已推出的 Gilenya 仿製藥的進入在美國。據您所知，Gilenya 第三季度在美國的銷售額為 3.26 億美元。

On Slide 25, I would like to provide an update on the other key financial elements of our expected core net income performance. As indicated on the Q2 call, we expect core net financial expenses to be slightly lower than in 2021, around $100 million to $150 million favorable versus 2021, revised from broadly in line versus 2021. And this change is mainly due to the higher financial income from reinvesting the proceeds of the Roche divestment and increased interest income for deposits. And the 2022 core tax rate is now expected to be around 16.5%, revised from the 17% to 17.5% range. This is mainly driven by a favorable change in the geographical profit mix.

在幻燈片 25 上，我想提供有關我們預期核心淨收入表現的其他關鍵財務要素的最新信息。如第二季度電話會議所示，我們預計核心淨財務費用將略低於 2021 年，與 2021 年相比有利約 1 億美元至 1.5 億美元，與 2021 年大致一致。這一變化主要是由於財務收入增加將羅氏撤資的收益進行再投資並增加存款的利息收入。現在預計 2022 年的核心稅率約為 16.5%，從 17% 修正為 17.5%。這主要是由於地域利潤組合的有利變化。

On Slide 26, I want to provide an update on expected currency impacts if currencies stay at current levels. Obviously, currency impacts are significant this year given the strength in U.S. dollar against many, if not all, currencies. For quarter 4, if currencies stay as they are now, we expect sales to be impacted by negative 9% and core operating income by negative 11% points. For the full year, we estimate the impact on the top line to be negative 7 points, on the bottom line, negative 8 points. Now into '23, we would expect the sales to be impacted by negative 4% and the bottom line negative 5% versus 2022. As a reminder, as currencies move quite dynamically, we update currency impacts every month on our website.

在幻燈片 26 上，如果貨幣保持在當前水平，我想提供有關預期貨幣影響的最新信息。顯然，鑑於美元兌許多（如果不是全部）貨幣走強，今年的貨幣影響很大。對於第四季度，如果貨幣保持現狀，我們預計銷售額將受到負 9% 的影響，核心營業收入將受到負 11% 的影響。對於全年，我們估計對頂線的影響為負 7 點，對底線的影響為負 8 點。現在到 23 年，我們預計與 2022 年相比，銷售額將受到負 4% 的影響，底線為負 5%。提醒一下，隨著貨幣的動態變化，我們每個月都會在我們的網站上更新貨幣影響。

And with that, I hand back to Vas.

有了這個，我交還給 Vas。

Thank you, Harry. So moving to Slide 28. Just as a reminder, at our recent meet the management, we articulated our new Novartis strategy, high-value medicines, greatest disease burdens through technology, leadership in R&D and novel access approaches, a focused therapeutic area mindset across 5 core therapeutic areas, 2 plus 3 technology platforms in 4 priority geographies and a renewed focus on high-value medicines, not necessarily volume of medicines, but delivering truly high-value medicines, along with the other elements of our strategy on delivering returns and strengthening the foundation.

謝謝你，哈利。所以轉到幻燈片 28。提醒一下，在我們最近的管理層會議上，我們闡述了我們的新諾華戰略、高價值藥物、通過技術帶來的最大疾病負擔、研發領導力和新的獲取方法、專注於治療領域的思維方式5 個核心治療領域，4 個優先地區的 2 + 3 個技術平台，重新關注高價值藥物，不一定是藥物數量，而是提供真正的高價值藥物，以及我們提供回報和戰略的其他要素加強基礎。

And translating that into this year's priorities on to Slide 29. We continue to maintain our growth momentum, and we confirm our 2022 guidance. Our top 22 priorities remain on track across launches and growth momentum on our 6 key brands. The pipeline is progressing per plan. I think the focused strategy, as I mentioned, has been executed against, and we're on track with the spin of Sandoz planned for next year. We continue our productivity plans through our new organizational model, delivering $1.5 billion of additional savings. And we continue to strengthen the foundations of the company, culture driving performance, data science to drive value and working towards ESG leadership.

並將其轉化為今年幻燈片 29 的優先事項。我們繼續保持增長勢頭，並確認我們的 2022 年指導。我們的 22 大優先事項在我們 6 個主要品牌的發布和增長勢頭中保持正常。管道正在按計劃進行。我認為，正如我所提到的，重點戰略已經被執行，我們正在按計劃在明年推出 Sandoz。我們通過新的組織模式繼續我們的生產力計劃，額外節省了 15 億美元。我們將繼續加強公司的基礎、文化推動績效、數據科學推動價值並努力實現 ESG 領導地位。

So with that, I will open the line for questions. I would ask that questioners please limit yourself to 1 question, and then we'll try to move through the queue as many rounds as we can in the call. Thank you.

因此，我將打開問題線。我會要求提問者將自己限制在 1 個問題上，然後我們將嘗試在電話中盡可能多地通過隊列。謝謝你。

(Operator Instructions) We will now take our first question. And your first question comes from Graham Parry from Bank of America.

（操作員說明）我們現在將回答第一個問題。您的第一個問題來自美國銀行的 Graham Parry。

So it's on Pluvicto. So very strong launch. Obviously, that's not inventory because you can't build inventory on Pluvicto. So I was wondering actually, has this caused any capacity constraints given you're only supplying from the Italian facility at the moment? And therefore, could we expect actually sales to (inaudible) quarter until you see new capacity come online? If you could just give us an update on the timing of the New Jersey and Indianapolis plants next year, are they still second quarter in the second half? Anything you can do to bring those online faster?

所以它在 Pluvicto 上。所以非常強大的發射。顯然，這不是庫存，因為您無法在 Pluvicto 上建立庫存。所以我實際上想知道，鑑於您目前僅從意大利工廠供應，這是否會導致任何產能限制？因此，在您看到新產能上線之前，我們能否預計實際銷售額將達到（聽不清）季度？如果你能告訴我們明年新澤西和印第安納波利斯工廠的時間更新，他們在下半年仍然是第二季度嗎？您可以做些什麼來讓這些網站更快上線？

Yes. Thanks, Graham. So with respect to Pluvicto, we're able to supply the U.S. demand across the 150 -- 125-plus centers now we have currently set up. And we would expect demand growth to continue in quarter 4. So we're able to make that supply. What's critical for us is as we move into the period where we hope to have a positive readout in the earlier lines of PSMAfore study, we would need additional capacity to be able to service that earlier, large indication.

是的。謝謝，格雷厄姆。因此，就 Pluvicto 而言，我們現在已經建立了 150 至 125 多個中心，能夠滿足美國的需求。我們預計需求將在第四季度繼續增長。所以我們能夠提供這種供應。對我們來說至關重要的是，當我們進入希望在 PSMAfore 研究的早期階段獲得積極讀數的時期時，我們需要額外的能力來服務於更早的大型指示。

Right now, we hope to be able to file the Millburn facility back to the Pluvicto file before the end of this year, and hope to have that online in the first part of next year. And we're on track for the Indianapolis facility to come online in the middle of next year. So once the Millburn facility comes online, we've invested in that facility to have additional capacity, we would be well positioned already for that new indication and the demand surge. And then once Indianapolis comes online, we would be in a position where we can service the U.S. from 2 manufacturing plants in the U.S., dedicate our European facilities to Europe and ex U.S., and then look at adding additional capacity in Asia and other markets over time. Thank you, Graham.

目前，我們希望能夠在今年年底之前將 Millburn 設施重新歸檔到 Pluvicto 文件中，並希望在明年上半年將其上線。我們有望在明年年中讓印第安納波利斯工廠上線。因此，一旦 Millburn 設施上線，我們已經對該設施進行了投資以增加產能，我們已經為新的適應症和需求激增做好了準備。然後，一旦印第安納波利斯上線，我們將能夠從美國的 2 家製造工廠為美國提供服務，將我們的歐洲工廠專用於歐洲和美國以外的地區，然後考慮在亞洲和其他市場增加額外的產能時間。謝謝你，格雷厄姆。

Your next question comes from the line of Wimal Kapadia from Bernstein.

您的下一個問題來自 Bernstein 的 Wimal Kapadia。

Can I just ask about Zolgensma, please. So some of your commentary, Vas, now suggests you've penetrated a large part of the bonus pool, and it's really about the incident population moving forward. I think it's probably fair to say, or please correct me, it's not that previously the $2 billion peak sales guide ex the intrathecal was a fair estimate. That's you are now saying $1.5 billion to $2 billion. So I just want to be clear, is that a change in expectations? And particularly given we're going to get close to $1.5 billion this year alone. And then just maybe, you mentioned Brazil, which are the key countries and maybe some timing on those countries would be great.

我能問一下 Zolgensma 的事嗎？所以你的一些評論，Vas，現在表明你已經滲透了大部分獎金池，這真的是關於事件人口的前進。我認為這可能是公平的，或者請糾正我，這並不是說以前 20 億美元的鞘內銷售高峰指南是一個公平的估計。那就是你現在說的 15 億到 20 億美元。所以我只想說清楚，這是期望的變化嗎？尤其是考慮到我們僅今年一年就將接近 15 億美元。然後也許，你提到了巴西，它們是關鍵國家，也許這些國家的一些時機會很好。

Yes, absolutely. So the dynamics on Zolgensma, as you all well know, we just to go through them, is that we -- as we add markets, we initially penetrate a bolus of patients in the under 2 age group, and then we move back to the incident patient population. And in the incident patient population, the demand is driven by expanding newborn screening, particularly outside of the United States.

是的，一點沒錯。所以大家都知道，Zolgensma 的動態是，我們只是通過它們——當我們增加市場時，我們最初會滲透到 2 歲以下年齡段的患者，然後我們回到事件患者人群。在事故患者群體中，需求是由擴大新生兒篩查推動的，特別是在美國以外的地區。

Right now, the key for us is to add those additional markets. So those markets range from Saudi Arabia and Brazil to Turkey and India. So there's a number of markets and other markets around the world where we're currently in active negotiation. And our hope is by adding those markets online, we'll be able to build that overall pool, not only of prevalent patients, which will increase sales for a period of time, but also build up the base of incident patients who are receiving Zolgensma on an ongoing basis.

現在，我們的關鍵是增加這些額外的市場。因此，這些市場範圍從沙特阿拉伯和巴西到土耳其和印度。因此，我們目前正在積極談判世界各地的許多市場和其他市場。我們希望通過在線添加這些市場，我們將能夠建立整體池，不僅是流行患者，這將在一段時間內增加銷售額，而且還建立正在接受 Zolgensma 的事件患者的基礎在現有基礎上。

I think as we now look at the trajectory, we're ranging just because we -- it's hard for us to predict exactly as we learn more when exactly these markets will come online. So we think it's prudent to say $1.5 billion to $2 billion. We certainly have the aspiration to get to $2 billion, but it's going to depend on how many more markets we're actually able to get on to national programs. And of course, our teams are working very hard to do that.

我認為，當我們現在查看軌跡時，我們之所以進行測距只是因為我們 - 當我們了解更多這些市場何時上線時，我們很難準確預測。因此，我們認為謹慎的說法是 15 億至 20 億美元。我們當然有達到 20 億美元的願望，但這將取決於我們實際上能夠進入多少國家項目的市場。當然，我們的團隊正在努力做到這一點。

We're currently enrolling the intrathecal indication for a 2- to 18-year olds, as I mentioned, both to generate additional data for IV, where we do have a broader label in certain markets, including the EU, up to 5 years of age. We want to generate additional data for the IV and the pivotal study and 2 to 18 year olds.

正如我所提到的，我們目前正在為 2 至 18 歲的兒童招募鞘內適應症，以生成更多的 IV 數據，我們在某些市場（包括歐盟）確實擁有更廣泛的標籤，最長可達 5 年年齡。我們希望為 IV 和關鍵研究以及 2 至 18 歲的兒童生成更多數據。

And we remain on track. We hope to have that filing in 2024 and then approved in the first part of 2025. And that would give us the momentum to make the medicine beyond $2 billion over time. And I think we'll have a better sense of how large it could be depending on the magnitude of the effect we see in those indications. Thanks for the question, Wimal.

我們仍然在軌道上。我們希望在 2024 年提交該申請，然後在 2025 年上半年獲得批准。這將使我們有動力隨著時間的推移使藥物超過 20 億美元。而且我認為我們會更好地了解它可能有多大，這取決於我們在這些跡像中看到的影響程度。謝謝你的問題，維馬爾。

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

您的下一個問題來自法國巴黎銀行的 Richard Parkes。

Just a question on Iptacopan in PNH. You've outlined the data for us on measures of extravascular hemolysis, but I wondered if you could give us any indication on how data on measures of intravascular hemolysis, such as LDH and rate of breakthrough hemolysis were trending. I know you'll present the data, but just wondering if you've got confidence there's at least no deterioration in those measures when switching from standard of care. And maybe you could just give us a sense of how you think about the launch uptake in that indication given we have standard of care with long-term outcomes data beyond control of anemia.

只是一個關於 PNH 中 Iptacopan 的問題。您已經為我們概述了有關血管外溶血測量的數據，但我想知道您是否可以向我們說明有關血管內溶血測量數據（例如 LDH 和突破性溶血率）的趨勢。我知道您會提供數據，但只是想知道您是否有信心從標準護理轉換時這些措施至少沒有惡化。也許您可以讓我們了解您如何看待該適應症中的啟動吸收，因為我們擁有超出控制貧血的長期結果數據的護理標準。

Yes. Thanks, Richard. So first, I think it's worth remembering that in Phase IIb as -- in the Phase IIb data sets for Iptacopan, Iptacopan demonstrated strong LDH lowering and a very favorable safety profile also with respect to breakthrough hemolysis. Given that we are in the midst of filing this data or submitting this data for congresses, I don't want to...

是的。謝謝，理查德。因此，首先，我認為值得記住的是，在 IIb 期中，在 Iptacopan 的 IIb 期數據集中，Iptacopan 表現出強烈的 LDH 降低以及在突破性溶血方面也非常有利的安全性。鑑於我們正在提交這些數據或向大會提交這些數據，我不想......

(technical difficulty)

（技術難度）

Update on the secondary endpoints. We'll present all of that as soon as possible in an upcoming medical meeting. But we feel very confident about the overall safety profile of Iptacopan with respect to the various other elements that one would want to measure across intravascular and extravascular hemolysis. Importantly as well, what will be important is an upcoming data set in the frontline setting in treatment-naive patients to demonstrate that the profile holds up.

次要終點的更新。我們將在即將召開的醫學會議上盡快介紹所有這些。但我們對 Iptacopan 的整體安全性非常有信心，因為人們希望在血管內和血管外溶血中測量其他各種因素。同樣重要的是，重要的是即將在未接受治療的患者的前線設置中的數據集，以證明該概況成立。

Taken together, based on everything that we've seen thus far, we -- our aspiration remains to be a medicine that can be used in naive patients, in patients -- to switch patients off of anti-C5s on to what we believe could be a more beneficial therapy. And then if desired, it can also be used as an add-on therapy to really cover the full range of potential indications with this medicine, a twice-a-day oral medicine, that we think can be really an attractive option, not only in the U.S., but would also when you consider that half of the PNH market is currently an ex U.S. market, a twice-a-day oral could be highly, highly attractive.

綜上所述，基於我們迄今為止所看到的一切，我們——我們的願望仍然是成為一種可用於天真患者、患者的藥物——將患者從抗 C5 切換到我們認為可以成為一種更有益的療法。然後，如果需要，它也可以用作附加療法，以真正涵蓋這種藥物的全部潛在適應症，一種每天兩次的口服藥物，我們認為這確實是一個有吸引力的選擇，不僅在美國，但當您考慮到 PNH 市場的一半目前是美國以外的市場時，一天兩次的口頭可能會非常非常有吸引力。

So all things to work through. We look forward to presenting the data in more detail shortly. Thanks, Richard.

所以所有事情都要解決。我們期待盡快提供更詳細的數據。謝謝，理查德。

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

您的下一個問題來自德意志銀行的 Emmanuel Papadakis。

Perhaps I could take one on Leqvio. We don't seem to see much of an impact from the first of July J-code award. So just your latest perspective on how things are trending and what confidence on what actually drives that mid-'23 inflection? Is there something that in your view is going to capitalize a step change in the middle of next year? Or is it more really a build through the course of 2023 and your confidence that we'll still get to blockbuster status pre-outcomes data in '26?

也許我可以在 Leqvio 上拿一個。我們似乎沒有看到 7 月第一屆 J-code 獎的影響很大。那麼，您對事物趨勢的最新看法以及對實際推動 23 世紀中期拐點的因素有什麼信心？在您看來，是否有什麼東西可以利用明年年中的一步變化？還是說它是 2023 年整個過程的真正構建，以及您對我們仍將在 26 年獲得重磅成果前結果數據的信心？

Thanks, Emmanuel. The key here is to get enough physicians who have gone through the process of getting a patient on therapy, both then seeing the LDL reduction after the first and second dose. Second dose is at the 3-month time point, and having successfully been reimbursed in the Part B program. When those things happen, we see physicians, 80% plus of physicians, at least that we've internally surveyed, have a positive experience, both from a clinical standpoint and from a Part B reimbursement standpoint, regardless of whether they used an alternative injection center or used their own clinic.

謝謝，伊曼紐爾。這裡的關鍵是讓足夠多的醫生經歷過讓患者接受治療的過程，然後在第一次和第二次給藥後看到 LDL 降低。第二劑是在 3 個月的時間點，並且已在 B 部分計劃中成功報銷。當這些事情發生時，我們看到醫生，80% 以上的醫生，至少在我們內部調查過的醫生中，無論從臨床角度還是從 B 部分報銷的角度來看，都有積極的體驗，無論他們是否使用替代注射劑中心或使用他們自己的診所。

So that's all the positive data that we have, but we need to move physicians through that process. So the reason we highlight 4,000 physicians now have initiated shows that we have that kind of -- in the early part of the funnel physicians moving through the process, they probably trialed a few patients. We now had to get them through that entire process. And if they presumably have that positive overall experience, they will add additional patients on to the therapy.

這就是我們擁有的所有積極數據，但我們需要讓醫生完成這個過程。因此，我們強調現在已經啟動的 4,000 名醫生的原因表明，我們有這種情況——在漏斗醫生的早期階段，他們可能對一些患者進行了試驗。我們現在必須讓他們完成整個過程。如果他們大概有這種積極的整體體驗，他們將增加更多的患者進行治療。

And so this is going to be a build. But as we build that base, we hope then to convert entire practices over to using Leqvio over time. And that would hopefully then lead to a compounding effect and an acceleration. Overall, we remain confident that we will get to the blockbuster status ahead of outcomes data, that's for certain. And a lot of work to do, but it absolutely remains our goal. Thanks, Emmanuel.

所以這將是一個構建。但隨著我們建立這個基礎，我們希望隨著時間的推移將整個實踐轉變為使用 Leqvio。這有望導致複合效應和加速。總體而言，我們仍然有信心在結果數據之前達到重磅炸彈狀態，這是肯定的。還有很多工作要做，但這絕對是我們的目標。謝謝，伊曼紐爾。

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

您的下一個問題來自瑞士信貸的 Matthew Weston。

I am going on follow on with Emmanuel's question, again touching on Leqvio. So Vas, as you pointed out, the market inflection not until 18 months into launch. As I recall, going back to Diovan and Entresto, I thought they took 4 years to breakeven as products. And now we have the risk of the IRA potentially limiting small molecule life to 9 years. Can you just lay out whether or not you feel that Leqvio will breakeven before that 4-year level we saw with large cardiovascular medicines? And if so, why?

我將繼續回答 Emmanuel 的問題，再次談到 Leqvio。因此，正如您所指出的，Vas 市場在推出 18 個月後才會出現拐點。我記得，回到 Diovan 和 Entresto，我認為他們需要 4 年的時間才能實現收支平衡。現在我們面臨 IRA 可能將小分子壽命限制為 9 年的風險。您能否說明您是否認為 Leqvio 會在我們看到的大型心血管藥物達到 4 年水平之前實現盈虧平衡？如果是這樣，為什麼？

And then I guess the other question is whether having invested so heavily in buy and bill, are there other cardiovascular assets that you hope to bring on board or have in the pipeline that you can put through the similar channel to give doctors the comfort that investing in all the practice infrastructure isn't just a single product with Leqvio, but there's a stream of products that they can capitalize on.

然後我想另一個問題是，是否在購買和賬單上投入瞭如此多的資金，是否還有其他心血管資產你希望引入或正在籌備中，你可以通過類似的渠道讓醫生放心投資在所有實踐中，基礎設施不僅僅是 Leqvio 的單一產品，而是他們可以利用的一系列產品。

Yes. Thanks, Matthew. So first, on the payback period, I'll have Harry comment, and I'll come back on the second part of your question.

是的。謝謝，馬修。所以首先，關於投資回收期，我會讓 Harry 發表評論，然後我會回到你問題的第二部分。

Matthew, I think we -- as we discussed before, these cardiovascular launches, in my experience, like GP primary care launches, and of course all of them are different depending on the product and the category and so on, but in my experience, usually then the breakeven happens roughly in year 4 plus/minus. While, of course, high-priced specialty launches sometimes have a breakeven in year 1 or at least in year 2.

馬修，我認為我們 - 正如我們之前討論的那樣，根據我的經驗，這些心血管產品的推出，就像 GP 初級保健產品的推出一樣，當然，它們都因產品和類別等而有所不同，但根據我的經驗，通常，盈虧平衡大約發生在第 4 年加/減。當然，高價推出的專業產品有時會在第一年或至少在第二年實現盈虧平衡。

So clearly, 9 years versus 13 years is not a positive, right? That's why I think also there will be initiatives to move those closer to the 13 years, both of them. But at the moment, it's 9 years. But of course, in any of these launches, one wants to have the uptake to be as fast as possible, just cardiovascular is slow. And I would expect the usually breakeven in year 4.

很明顯，9 年對 13 年不是積極的，對吧？這就是為什麼我認為還會有一些舉措讓它們更接近 13 年，兩者都是。但目前，已經9年了。但是，當然，在任何這些發布中，人們都希望盡可能快地吸收，只是心血管疾病的速度很慢。我預計通常會在第 4 年實現盈虧平衡。

I think, Matthew, in terms of having -- it is on our mind to build a broader portfolio of medicines. So both in-house, we have efforts ongoing both in terms of life cycle management of Leqvio as well as other novel therapeutics, which are still moving through the research pathway or research labs to try to accelerate now to make sure we have a stream of medicines. I also say broadly in the industry, there are other medicines as well that I think would also fit in terms -- into the buy-and-bill model.

我認為，馬修，就擁有 - 我們的想法是建立更廣泛的藥物組合。因此，無論是在內部，我們都在 Leqvio 的生命週期管理以及其他新療法方面正在進行努力，這些新療法仍在研究途徑或研究實驗室中，以嘗試加速，以確保我們擁有源源不斷的藥物。我還廣泛地說，在該行業中，我認為還有其他藥物也適合 - 購買和賬單模型。

But on a stand-alone basis, for most practices that we've analyzed, the number of cholesterol patients in a practice, it is favorable for cardiologists once they have the setup and have it moving to do it just for Leqvio. So I think it's an important point that it's not a requirement that you have multiple medicines. Even this one medicine alone, where you have also the certainty that you know the patient is on therapy, you see the result on the cholesterol lowering. It's highly attractive from that point clinically. And also the practice has the cost reimbursement elements as well. It's pretty attractive, we find with most practices that have gone through the process.

但在獨立的基礎上，對於我們分析過的大多數實踐，一個實踐中的膽固醇患者數量，一旦心髒病專家有了設置並讓它為 Leqvio 做這件事，這對他們來說是有利的。所以我認為重要的一點是，你不需要擁有多種藥物。即使只有這一種藥物，您也可以確定您知道患者正在接受治療，您會看到降低膽固醇的結果。從那時起，它在臨床上非常有吸引力。而且這種做法也有費用報銷的要素。它非常有吸引力，我們發現大多數實踐都經歷了這個過程。

So we'll not only focus on Leqvio, but also build a pipeline behind it. And as Harry mentioned, I think a top priority has to be to ensure small molecules and related technologies are not penalized relative to large molecules. So that, of course, will take time to shape public policy. Thanks, Matthew.

因此，我們不僅會關注 Leqvio，還會在其背後建立一個管道。正如哈里所說，我認為當務之急是確保小分子和相關技術相對於大分子不會受到懲罰。當然，這需要時間來塑造公共政策。謝謝，馬修。

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

您的下一個問題來自 Redburn 的 Simon Baker。

And the risk of being boring, I'm going to follow Matthew and Emmanuel on Leqvio. Vas, just on this -- your expectation of a linear trend to the middle of next year, with the 2 drivers of more doctors being set up to administer the drug and more patients per physician, I mean that does sound a little conservative because, I mean, that in itself should -- if both of those are increasing, that should drive more than linear growth. So I'm just trying to understand a little bit more about that.

還有無聊的風險，我將在 Leqvio 上關注 Matthew 和 Emmanuel。 Vas，就在這一點上——你對明年年中的線性趨勢的預期，隨著更多醫生的兩個驅動因素被設置來管理藥物，每個醫生有更多的病人，我的意思是這聽起來有點保守，因為，我的意思是，這本身應該 - 如果兩者都在增加，那應該推動的不僅僅是線性增長。所以我只是想多了解一點。

And also related to that, you are running a DTC campaign with 2 adverts at the moment in the U.S. for Leqvio. Do you have any sense of how patient demand is exceeding the billing capabilities of physicians at the moment? It's not really the case of unfilled scripts, but unsatisfied patient demand. Is there any indication you can give us on that?

與此相關的是，您目前正在美國為 Leqvio 投放包含 2 個廣告的 DTC 廣告系列。您是否知道目前患者的需求如何超過了醫生的計費能力？這不是未填寫的腳本的情況，而是未滿足的患者需求。你有什麼跡象可以告訴我們嗎？

Yes, Simon. I think on the first question, I think it's just -- we've learned over the years, it's prudent on cardiovascular launches to be appropriately cautious until we see evidence that in the sales line, we see a trend break. And I think at the moment, all of the inputs look positive, as you say. We have the number of physicians that we have that have initiated some action on Leqvio, the feedback we get from physicians going through the process. We're starting to see improvements, so we'd like to see more improvements in depth per practice that are on, that are using Leqvio already.

是的，西蒙。我認為關於第一個問題，我認為這只是 - 我們多年來了解到，在我們看到銷售線出現趨勢突破的證據之前，心血管產品的發布要謹慎謹慎。正如你所說，我認為目前所有的輸入看起來都是積極的。我們有很多醫生已經對 Leqvio 採取了一些行動，我們從經歷過這個過程的醫生那裡得到了反饋。我們開始看到改進，所以我們希望看到每個練習的深度改進，這些改進已經在使用 Leqvio。

So all of the things are in the right direction. Reimbursement is at higher levels than PCSK9s achieved in year 5. We've said high levels of patients don't have to pay any co-pay to access the medicine. So again, all in the right direction. But I think we would feel better if we actually saw a trend break before we start promising anything bigger than a linear trend. So that's kind of our mindset at the moment. And if it happens, that would be terrific and we, of course, share that with all of you as soon as it does.

所以所有的事情都朝著正確的方向發展。報銷水平高於第 5 年達到的 PCSK9。我們已經說過，高水平的患者無需支付任何共付額即可獲得藥物。再說一次，一切都朝著正確的方向發展。但我認為，如果我們在開始承諾比線性趨勢更大的東西之前真正看到趨勢突破，我們會感覺更好。所以這就是我們目前的心態。如果它發生了，那就太棒了，我們當然會盡快與大家分享。

We do have a very active DTC campaign to activate patients on the benefits of a twice-a-year therapy that can deliver up to 60% lowering on LDL cholesterol. We do see the beginnings of increased patient demand. I would note that, actually, we don't see capacity as an issue because we are able to use the AIC networks, which are continuing to expand to absorb any excess patient volume. So if a practice is not able to set a buy and bill immediately, we're able to educate practices about AICs, which are available in the community that are set up. And we've worked very closely with that expanding network of alternative injection centers to make Leqvio available.

我們確實開展了一項非常積極的 DTC 活動，以使患者受益於每年兩次治療的好處，這種治療可以降低 60% 的低密度脂蛋白膽固醇。我們確實看到了患者需求增加的開始。我要指出的是，實際上，我們並不認為容量是一個問題，因為我們能夠使用 AIC 網絡，該網絡正在繼續擴大以吸收任何多餘的患者數量。因此，如果一個實踐不能立即設置購買和計費，我們能夠教育有關 AIC 的實踐，這些實踐在已建立的社區中可用。我們與不斷擴大的替代注射中心網絡密切合作，以提供 Leqvio。

One of the things we've learned that we need to get much smoother at is that transition of helping a practice that send the patient to the AIC and then back to the practice. We're working on smoothing that out. But that AIC creates a pretty big surge capacity. But what we do hear from practices in general is, over time, they would like to set up the buy-and-build capacity within their own practice. It's just a matter of can they do that immediately? Or would they like to do that in the future? Thanks, Simon.

我們了解到，我們需要更順利地完成的一件事是幫助將患者送到 AIC 然後返回實踐的實踐的過渡。我們正在努力解決這個問題。但該 AIC 創造了相當大的浪湧能力。但我們從實踐中聽到的一般情況是，隨著時間的推移，他們希望在自己的實踐中建立購買和構建能力。只是他們能立即做到嗎？或者他們將來願意這樣做嗎？謝謝，西蒙。

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

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

This is Richard Wagner, on behalf of Tim with Wolfe Research. It's about Cosentyx. And could we get an update on the competitive landscape in the U.S. as AbbVie works to lock in formulary positioning for its various I&I products in 2023 onwards as Humira biosimilars approach. What would be the impact or could be the impact on net pricing and formulary placement?

我是 Richard Wagner，代表 Tim with Wolfe Research。這是關於 Cosentyx 的。我們能否獲得美國競爭格局的最新信息，因為隨著 Humira 生物仿製藥的接近，艾伯維（AbbVie）致力於在 2023 年鎖定其各種 I&I 產品的處方定位。會對淨定價和處方集產生什麼影響或可能產生什麼影響？

Yes. Thanks, Richard. When you look at Cosentyx, we're still in the midst of the formulary negotiations at this time. But our best belief in indication, given that formularies want to have an IL-17A available for patients, that we'll be able to maintain our formulary position at roughly equivalent position in terms of our gross to net as we have this year.

是的。謝謝，理查德。當您查看 Cosentyx 時，我們此時仍處於處方談判中。但是，鑑於處方集希望為患者提供 IL-17A，我們對指示的最佳信念是，就我們今年的總淨額而言，我們將能夠將處方集位置保持在大致相當的位置。

I think looking forward, what will be absolutely critical for us to continue Cosentyx's growth dynamics and really maximize the medicine is the approval of additional indications in hidradenitis. We have the IV indication as well. As I mentioned, we plan to file -- we have a 2 ml syringe, which we're also in the midst of filing. Those would be the next big 3. And then beyond that, indications, as I mentioned, giant cell arteritis, tendinitis, amongst others. That's going to be the next wave we're going to need to maintain strong position on formularies, but also to enable the brand to continue to grow.

我認為展望未來，對於我們繼續 Cosentyx 的增長動力並真正最大限度地利用藥物而言，絕對關鍵的是批准更多的汗腺炎適應症。我們也有 IV 適應症。正如我所提到的，我們計劃提交——我們有一個 2 毫升的注射器，我們也在提交中。那些將是下一個大 3。然後除此之外，還有適應症，正如我提到的，鉅細胞動脈炎、肌腱炎等。這將是我們需要保持在處方集上的強勢地位的下一波浪潮，同時也使品牌能夠繼續發展。

But for 2023, based on our negotiations to date and reviews we've had with our managed market teams, we feel comfortable with where we'll be on formularies for next year.

但是對於 2023 年，根據我們迄今為止的談判以及與我們管理的市場團隊進行的審查，我們對明年的處方集感到滿意。

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

您的下一個問題來自 Cowen 的 Stephen Scala。

First, an observation, then a question. So the observation is that in response to the Pluvicto question, it makes it sound as though Q4 sales will be appreciably above Q3. And I guess you must have some visibility since Q4 is about 1/3 over already. The question is, Vas, in the past, you have been cautious on the use of A-beta antibodies for the treatment of Alzheimer's disease. Given recent news, do you have any reason to change your view? And if yes, then how will Novartis gain a position in A-beta antibodies or some other approach in Alzheimer's?

首先是觀察，然後是問題。因此，觀察結果是，在回答 Pluvicto 問題時，聽起來好像第四季度的銷售額將明顯高於第三季度。而且我想您一定有一定的知名度，因為第四季度已經超過了 1/3。問題是，Vas，過去，您對使用 A-β 抗體治療阿爾茨海默病一直持謹慎態度。鑑於最近的消息，你有什麼理由改變你的看法嗎？如果是的話，那麼諾華將如何在 A-beta 抗體或其他阿爾茨海默病治療方法中獲得一席之地？

Yes. Thanks, Steve. On the A-beta antibodies, I think what's most important, particularly given the amount of investment that would need to be made by health care systems for therapies, and we of course are active in Alzheimer's disease research, is the benefit that we're seeing not only statistically significant, but clinically meaningful. And I think with the various measures that are currently used, it's hard to judge what is clinically meaningful ultimately for a patient. And I think that's going to be the question for payers, advisers, et cetera, in the U.S. markets. Is this clinically meaningful enough? A very -- the 0.4, 0.45 or whatever the number is, on the ADAS, [ECOG] scores.

是的。謝謝，史蒂夫。關於 A-beta 抗體，我認為最重要的是，特別是考慮到醫療保健系統需要為治療進行大量投資，而且我們當然積極參與阿爾茨海默病研究，這是我們獲得的好處不僅具有統計學意義，而且具有臨床意義。而且我認為，根據目前使用的各種措施，很難判斷什麼最終對患者俱有臨床意義。我認為這將是美國市場上付款人、顧問等的問題。這在臨床上是否足夠有意義？在 ADAS 上，非常 - 0.4、0.45 或任何數字，[ECOG] 分數。

So I think we'll have to see. That will be for others to judge. Our focus is on other mechanisms of action. I mean we think -- we don't know, but certainly, our labs are working on other approaches across the full range of neurodegenerative diseases, where we have programs in the clinic, as you know, on Huntington's and Parkinson's, and continue to also look at various targets in Alzheimer's. But I wouldn't expect us to take any action on A beta, and none of the data that I've seen thus far would trigger us to make a shift at this point in time.

所以我想我們必須看看。這將由其他人來判斷。我們的重點是其他作用機制。我的意思是我們認為——我們不知道，但可以肯定的是，我們的實驗室正在研究各種神經退行性疾病的其他方法，如你所知，我們在臨床上有針對亨廷頓氏症和帕金森氏症的項目，並繼續也看看阿爾茨海默氏症的各種目標。但我不希望我們對 A beta 採取任何行動，而且到目前為止我看到的任何數據都不會觸發我們在這個時間點做出改變。

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

您的下一個問題來自 Berenberg 的 Kerry Holford。

Question for Harry. Just looking at the UNR844 termination, that product that you acquired by the Encore Vision acquisition. Was there an asset impairment taken in the quarter? And if not, is that coming next quarter? I wonder if you can quantify how big that might be.

哈利的問題。只需查看 UNR844 終端，即您通過 Encore Vision 收購獲得的產品。本季度是否發生資產減值？如果沒有，那是下個季度嗎？我想知道你是否可以量化這可能有多大。

Yes. Thank you, Kerry. Actually, the majority of our impairment recorded in quarter 3 was UNR. The potential presbyopia drops of roughly net impact of $0.5 billion. So we immediately, when we stopped the program, we immediately booked it. So that has happened in quarter 3.

是的。謝謝你，克里。實際上，我們在第三季度記錄的大部分減值是 UNR。潛在的老花眼減少了大約 5 億美元的淨影響。所以我們立即，當我們停止該計劃時，我們立即預訂了它。所以這發生在第三季度。

Great. Thank you, Kerry.

偉大的。謝謝你，克里。

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

您的下一個問題來自摩根大通的 Richard Vosser。

Maybe we could talk about NATALEE. And maybe you could give us an update where we are in terms of the interim analysis. Is it still the case that the 70% interim should be expected at the end of the year? And then, of course, the final analysis within the second half of next year? Just some thoughts there would be great.

也許我們可以談談娜塔莉。也許您可以向我們提供中期分析方面的最新信息。 70%的中期還是應該在年底預期嗎？然後，當然是明年下半年內的最終分析？只是一些想法會很棒。

Yes. Thanks, Richard. So we continue to expect the first interim to read out before the end of this year. But we have not heard back from the DMC at this point in time. And our approach will be that if the DMC advises us to make a change, we'll let the markets know. And if you don't hear from us, that means the DMC told us that the study should continue as planned. We expect the second interim to happen in the first half of next year and the final study should complete at the second half of next year.

是的。謝謝，理查德。因此，我們繼續預計第一個中期將在今年年底之前宣讀。但我們目前還沒有收到 DMC 的回复。我們的做法是，如果 DMC 建議我們做出改變，我們會讓市場知道。如果您沒有收到我們的消息，這意味著 DMC 告訴我們，研究應該按計劃繼續進行。我們預計第二個中期將在明年上半年進行，最終研究應在明年下半年完成。

Another study that -- another question that often comes up is related to how we'll approach OS in these various settings. And the FDA has confirmed to us that as long as there is no detriment to OS at any of these time points, that would be sufficient for them to consider the data set as pivotal for a potential approval. Thanks, Richard.

另一項研究——另一個經常出現的問題與我們將如何在這些不同的環境中處理操作系統有關。 FDA 已經向我們確認，只要在任何這些時間點都沒有對 OS 造成損害，就足以讓他們將數據集視為潛在批准的關鍵。謝謝，理查德。

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

您的下一個問題來自巴克萊銀行的 Emily Field。

Just on MS. On Gilenya, I know your prior guidance assumed no launches in the U.S. So good to maintain that. Just the impact on core operating margin, should we think of that as a pretty straight drop down given that it's probably a pretty high-margin product? And then just on Kesimpta, your share assumptions in the class going forward, do you expect those to be impacted by the potential launch of subcutaneous Ocrevus?

就在MS上。在 Gilenya 上，我知道您之前的指導假設在美國沒有發射，所以很好地保持這一點。只是對核心營業利潤率的影響，鑑於它可能是一個利潤率相當高的產品，我們是否應該將其視為相當直接的下降？然後在 Kesimpta 上，你在課堂上的分享假設，你是否預計這些假設會受到皮下 Ocrevus 潛在推出的影響？

So first on Gilenya, Harry?

那麼首先在Gilenya，Harry？

Yes. Thank you, Emily. Yes, this is very -- it's a very high gross margin product. There's some royalty on it, but it's, of course, also small molecule, high priced. So the product margin is quite high. As you can imagine, at the end of the life cycle, there is not much M&S on it. So it's pretty much a straight drop down to the bottom line. But of course, we have mitigating actions and productivity plans, and it's fully embedded in our guidance this year.

是的。謝謝你，艾米麗。是的，這是非常 - 這是一個非常高的毛利率產品。它有一些版稅，但它當然也是小分子，價格高。所以產品利潤率相當高。可以想像，在生命週期結束時，它上面並沒有多少 M&S。因此，這幾乎是直接下降到底線。但是，當然，我們有緩解行動和生產力計劃，它完全嵌入我們今年的指導中。

And then with respect to Kesimpta, Kesimpta has really been successful as a first line for switch medicine in the neurology settings that are not currently participating in infusions, as is the case with our competitor product. I think first, we need to see if a high dose subcu can be delivered without any sort of reactions and other complications. I don't think that's a given. I mean, of course, data will have to bear that out.

然後就 Kesimpta 而言，Kesimpta 作為目前未參與輸液的神經病學環境中的開關藥物的一線藥物，確實是成功的，就像我們的競爭對手產品一樣。我認為首先，我們需要看看是否可以在沒有任何反應和其他並發症的情況下交付高劑量 subcu。我不認為這是給定的。我的意思是，當然，數據必須證明這一點。

And then it's worth remembering our positioning will be for patients who want a monthly injection at home and don't want to go into the infusion center. Clearly, the subcu might reduce the time of the infusion center, but it remains to be seen how will steroid pretreatment need to be happened. Will it need to be continued to be IV? Can it -- is it sufficient for it to be oral? What kind of monitoring requirements FDA will require?

然後值得記住的是，我們的定位將是針對希望在家中每月注射一次並且不想進入輸液中心的患者。顯然，subcu 可能會減少輸液中心的時間，但類固醇預處理需要如何進行仍有待觀察。是否需要繼續IV？它可以——它是口頭的就足夠了嗎？ FDA 將要求什麼樣的監測要求？

So I think it still remains that there is a segment of the market that will want to use IV infusion or subcu infusion therapies. And there's a segment where Novartis and Kesimpta, we hope to become the clear leader amongst patients first class -- first treatment or first switch who want a very convenient, at-home, highly safe, high efficacious B-cell therapy, and that's our focus. And Harry has a point.

因此，我認為仍有一部分市場希望使用 IV 輸液或 subcu 輸液療法。在諾華和 Kesimpta 的細分市場中，我們希望成為一流患者的明確領導者——第一次治療或第一次轉換，他們想要一種非常方便、在家中、高度安全、高效的 B 細胞治療，這就是我們的重點。哈利說得有道理。

Yes. Just Emily, a follow-on clarification also on Gilenya. I mentioned that this is fully in our guidance for 2022. I just want to mention also that this has no impact to our mid- to long-term guidance. Prior to this turn of the U.S. courts, if you will, we were expecting to lose U.S. exclusivity, if you will, or have generic entries in the middle of '24 roughly, right? From that standpoint, our 40% plus margin goal in 2027 plus was already fully assuming that generics would have ended several years before that.

是的。只是艾米麗，對 Gilenya 的後續澄清。我提到這完全包含在我們對 2022 年的指導中。我只想提一下，這對我們的中長期指導沒有影響。在美國法院輪換之前，如果您願意，我們預計會失去美國的排他性，或者在 24 年中期大致有通用條目，對吧？從這個角度來看，我們在 2027 年 40% 以上的利潤率目標已經完全假設仿製藥會在此之前幾年結束。

Great. Thanks, Harry. And so we still have a number of questions in the queue. (Operator Instructions).

偉大的。謝謝，哈利。因此，我們仍有許多問題待在隊列中。 （操作員說明）。

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

您的下一個問題來自高盛的 Keyur Parekh。

Vas, you mentioned that you would like for Iptacopan to be the therapy of choice kind of in the frontline setting. What data do you think you would need to see kind of from the frontline study to allow for Iptacopan to be in that position given the head start that the Alexion products already have in that market?

Vas，您提到您希望 Iptacopan 成為前線環境中的首選療法。鑑於 Alexion 產品已經在該市場佔據領先地位，您認為您需要從一線研究中看到哪些數據才能使 Iptacopan 處於該位置？

Yes. Thanks, Keyur. I think what will be important is if we can demonstrate we can generate clear control of the disease. And of course, across the various parameters, LDH, safety, et cetera, that we have a compelling profile. I think when you look broadly, first, if you think first principle, the biology of this disease, this is an alternative complement pathway-driven disease. And factor B is a relatively unique component of this, in that it's not as abundant as C3 and C5, and an oral agent can get to both to extravascular and intravascular sources of factor B and inhibit those. And those include tissues that go beyond the liver, which is an important consideration when you consider ASOs and siRNAs, and oral therapy presents a unique profile in being able to reach the full broad range of tissues.

是的。謝謝，凱爾。我認為重要的是，如果我們能夠證明我們可以明確控制這種疾病。當然，在各種參數、LDH、安全性等方面，我們都有令人信服的概況。我認為，如果您從廣義上看，首先，如果您首先考慮這種疾病的生物學原理，這是一種替代補體途徑驅動的疾病。而 B 因子是其中一個相對獨特的成分，因為它不如 C3 和 C5 豐富，並且口服劑可以同時到達血管外和血管內的 B 因子來源並抑制它們。其中包括肝臟以外的組織，當您考慮 ASO 和 siRNA 時，這是一個重要的考慮因素，而口服療法在能夠到達所有廣泛的組織方面呈現出獨特的特徵。

So overall, we think factor B for these alternative complement-driven diseases, including PNH, is an ideal target. And overall, the PK/PD we see for this medicine, the preclinical and clinical safety we see, has been very good. That's been borne out now in the APPLY-PNH study that we've already headlined. And we hope to continue to see that in the frontline study. And then next year in C3G, in particular, but also in IgAN. And then in other alternative complement pathway-driven diseases, including aHUS, (inaudible) gluten disease, [MC PGN].

因此，總的來說，我們認為這些替代補體驅動疾病（包括 PNH）的因子 B 是一個理想的目標。總的來說，我們看到的這種藥物的 PK/PD，我們看到的臨床前和臨床安全性非常好。這已經在我們已經成為頭條新聞的 APPLY-PNH 研究中得到證實。我們希望在一線研究中繼續看到這一點。然後是明年的 C3G，尤其是 IgAN。然後在其他替代補體途徑驅動的疾病中，包括 aHUS、（聽不清）麩質病、[MC PGN]。

So there's a range of diseases where we believe the medicine is well suited. And I think we're excited that the medicine has, so far in its first pivotal readout, borne out the clinical and preclinical hypotheses that we set forward. So we'll look forward to providing the data in an upcoming medical congress as I outlined. And then the second study as well will read out before the end of this year.

因此，我們認為該藥非常適合多種疾病。而且我認為我們很高興該藥物迄今為止在其第一次關鍵讀數中證實了我們提出的臨床和臨床前假設。因此，正如我所概述的，我們期待在即將召開的醫學大會上提供數據。然後第二項研究也將在今年年底之前宣讀。

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

您的下一個問題來自摩根士丹利的 Mark Purcell。

First, just returning to NATALEE, the interim analysis. Is that based on all comers? Or do you need to see a significant benefit specifically in the intermediate-risk patients, which may be, I guess, as low as 25%, 30% of the events?

首先，回到 NATALEE，中期分析。這是基於所有來者？或者您是否需要在中等風險患者中看到顯著的益處，我猜這可能低至 25%、30% 的事件？

Yes. So Mark, I think it's important to note that we're looking at both grade 2, grade 3 patients in the study. And the way we're powered is across the entire population. And we've relooked at powering many times now, and we feel very comfortable based on the study design and what we've seen from other competitors and the fact that we power it up by 1,000 additional patients. And so the results, the IDFS results, will be based on the overall population, and that's how the endpoints are designed.

是的。所以馬克，我認為重要的是要注意我們正在研究中的 2 級和 3 級患者。我們獲得動力的方式遍及整個人口。而且我們現在已經多次重新考慮供電，基於研究設計和我們從其他競爭對手那裡看到的情況以及我們通過增加 1,000 名患者為其供電的事實，我們感到非常自在。因此，IDFS 結果將基於總體人口，這就是端點的設計方式。

As a separate point, and just to be clear, the FDA, can, at any point in time, decide that they want to take cuts between stage 2 and stage 3 patients. But our focus for our primary analysis is stage IIa, stage IIb and stage III patients as defined in the protocol, and the endpoint will be driven off of that entire patient population.

作為一個單獨的點，並且需要明確的是，FDA 可以在任何時間點決定他們想要在第 2 階段和第 3 階段患者之間進行削減。但我們主要分析的重點是方案中定義的 IIa 期、IIb 期和 III 期患者，終點將被排除在整個患者群體之外。

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

您的下一個問題來自古根海姆證券公司的 Seamus Fernandez。

I guess one quick question just on Leqvio. Can you just help us understand where those patients are coming from? Are they predominantly switched patients from existing PCSK9 therapy? Or is this a new patient pool? And then just very quickly, second question. Vas, as we look towards potential business development becoming increasingly critical as the years progress, just wondering where your particular focus is given the commentary around primary care cardiovascular product launches and the ability to launch into those efficiently.

我想一個關於 Leqvio 的快速問題。你能幫我們了解這些病人來自哪裡嗎？他們是否主要將患者從現有的 PCSK9 療法中轉換出來？或者這是一個新的患者庫？然後很快，第二個問題。 Vas，隨著時間的推移，我們期待潛在的業務發展變得越來越重要，只是想知道您對初級保健心血管產品推出的評論以及有效推出這些產品的能力的特別關注點在哪裡。

Yes. Thanks, Seamus. So first, on Leqvio source of business. Just as a reminder, the target patient population in the U.S. is 18 million patients. And across all of the core markets, EU plus the top markets around the world, is around 70 million patients. These are patients who have had a prior cardiovascular event and are not reaching 70 milligrams per deciliter on their LDL score. And that is the guideline directed, that is the goal. So it's a big, big patient population.

是的。謝謝，西莫。首先，關於 Leqvio 的業務來源。提醒一下，美國的目標患者群體是 1800 萬患者。在所有核心市場中，歐盟以及全球頂級市場約有 7000 萬患者。這些患者既往有過心血管事件，且 LDL 評分未達到 70 毫克/分升。這就是指導方針，這就是目標。所以這是一個龐大的患者群體。

Right now, I think what we can say is that the primary prescribers that we see are prescribers who also have experience with PCSK9 monoclonal antibodies. That could be low experience, it could be high experience, harder for us to say given that this is a Part B medicine, the source of business from a patient standpoint. But I presume then we're either getting switch patients on PCSK9 monoclonal antibodies, or we're at least getting a broader share of physicians that are open to the PCSK9 class.

現在，我認為我們可以說的是，我們看到的主要處方者是也有使用 PCSK9 單克隆抗體經驗的處方者。這可能是低經驗，也可能是高經驗，鑑於這是 B 部分藥物，從患者的角度來看，這是業務的來源，我們很難說。但我想我們要么讓轉換患者使用 PCSK9 單克隆抗體，要么我們至少得到更廣泛的對 PCSK9 類別持開放態度的醫生。

And so our focus right now is to really say how can we get broad adoption within, let's call it, PCSK9-minded physicians. And then over time, try to expand further and further through our work with systems of care, population health agreements, et cetera, into the broader patient population of 18 million patients.

因此，我們現在的重點是真正說明我們如何在具有 PCSK9 意識的醫生內部得到廣泛採用。然後隨著時間的推移，嘗試通過我們與護理系統、人口健康協議等方面的合作，進一步擴大到更廣泛的 1800 萬患者群體。

Clearly, we don't need that bigger share of that 18 million patients to reach our overall financial goals. From a public health standpoint, we would, of course, want to [reset] many of those patients as possible, because right now, the odds of a patient having a subsequent event go up quite dramatically if they're not at that 70 goal. So that's kind of overall how we approach it.

顯然，我們不需要這 1800 萬患者中更大的份額來實現我們的整體財務目標。從公共衛生的角度來看，我們當然希望盡可能多地[重置]這些患者，因為現在，如果患者沒有達到 70 的目標，他們發生後續事件的機率會大大增加.這就是我們處理它的整體方式。

There's no updates with respect to M&A and BD. We continue to focus on, let's call them, sub-$3 billion, $4 billion M&A deal, broad range licensing opportunities, focused primarily on science and does the science work? Is it fitting in our core therapeutic areas? Does it fit in our 2 plus 3 technology areas as we've outlined that to meet the management. And we continue to assess. Then if we find something that's attractive, where we have a differentiated view that would justify the premium and generate, we believe, value creation for our shareholders, we'll, of course, pursue it.

沒有關於併購和 BD 的更新。我們繼續關注（我們稱之為）低於 30 億美元、40 億美元的併購交易、廣泛的許可機會，主要關注科學，科學是否有效？它適合我們的核心治療領域嗎？它是否符合我們為滿足管理層而概述的 2 加 3 技術領域。我們繼續評估。然後，如果我們發現一些有吸引力的東西，我們有不同的觀點來證明溢價是合理的，並且我們相信，為我們的股東創造價值，我們當然會追求它。

Other than that, we're also willing to be patient. We believe in our pipeline. We believe with our new leadership within R&D and the addition of a Strategy and Growth Officer, we can unlock the full potential of Novartis research and development and then have a steady stream of medicines going forward. And so we're going to remain disciplined as we move ahead.

除此之外，我們也願意耐心等待。我們相信我們的管道。我們相信，憑藉我們在研發領域的新領導以及戰略和增長官的加入，我們可以釋放諾華研發的全部潛力，然後擁有源源不斷的藥物。因此，在我們前進的過程中，我們將保持自律。

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

您的下一個問題來自法國興業銀行的 Florent Cespedes。

Vas, a quick one on China, please. As China is a key country for you, could you please elaborate on the dynamic there for your key products and if there is any, let's say, impact from lockdowns? And could you refresh our memories and please remind us the current contribution and your ambition on this country?

Vas，請快速介紹一下中國。由於中國對您來說是一個關鍵國家，您能否詳細說明您的關鍵產品的動態，如果有任何影響，比如說，封鎖的影響？您能否喚醒我們的記憶，並請提醒我們當前的貢獻和您對這個國家的抱負？

Yes. With respect -- thanks, Florent. For China, we've outlined our aspiration to become a top 3 player by 2024, which would be a player that exceeds $4 billion in sales in the market. We've had really a record performance in terms of number of approvals over recent years. And then also moving forward, I think, we'll lead the industry as well in terms of NRDL listings. Key drivers for us has been our oncology portfolio, Entresto, Cosentyx, Lucentis, amongst others.

是的。尊重 - 謝謝，弗洛倫特。對於中國，我們已經概述了到 2024 年成為前 3 名玩家的願望，這將是一個市場銷售額超過 40 億美元的玩家。近年來，我們在批准數量方面確實取得了創紀錄的成績。然後，我認為，我們也將在 NRDL 列表方面引領行業。我們的主要驅動力是我們的腫瘤產品組合，Entresto、Cosentyx、Lucentis 等。

Now we were growing in the high teens from a sales growth standpoint before the lockdowns. And I think the lockdown -- we continue to grow, but we're growing more in the high single-digit frame at the moment. And we would expect that to continue until we would see a shift in the overall ability for patients to access medical care in more normal dynamics. That's part of the reason why you see the slowdown in Cosentyx that we saw.

現在，從鎖定之前的銷售增長的角度來看，我們正處於青少年時期。而且我認為鎖定-我們繼續增長，但目前我們在高個位數框架內增長更多。我們預計這種情況會持續下去，直到我們看到患者在更正常的情況下獲得醫療服務的整體能力發生轉變。這就是你看到我們看到的 Cosentyx 放緩的部分原因。

With Entresto, given the strength of our overall performance globally, it doesn't really move the needle on that particular brand. So the key brand where it has an impact is Cosentyx and, to a smaller extent, in some of the other brands.

有了 Entresto，考慮到我們在全球範圍內的整體表現實力，它並沒有真正推動那個特定品牌的發展。因此，它產生影響的關鍵品牌是 Cosentyx，在較小程度上，還有其他一些品牌。

Nonetheless, we continue to believe, given that there's over 1 billion patients -- 1 billion people we can serve with our portfolio of medicines, we have to continue to find ways to continue to reach patients in the framework that is currently in place. And then also be ready that if there's a further opening up, to continue to expand our growth in the market. And importantly, we believe Leqvio and some of our other medicines, Pluvicto, Leqvio, amongst others, could be significant medicines in China over time.

儘管如此，我們仍然相信，鑑於有超過 10 億患者——我們可以使用我們的藥物組合為 10 億人提供服務，我們必須繼續尋找方法在目前的框架內繼續接觸患者。然後也準備好，如果有進一步的開放，繼續擴大我們在市場上的增長。重要的是，我們相信 Leqvio 和我們的其他一些藥物，如 Pluvicto、Leqvio 等，隨著時間的推移可能成為中國的重要藥物。

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

您的下一個問題來自花旗銀行的 Andrew Baum。

A question on the IRA impact on catastrophic coverage and the burden on PBMs and managed care. A significant part of Kisqali goes through the Medicare channel. Ibrance seems to be available at a much lower price post genericization. To what extent -- to what extent, excuse me, do you see deflation of the price of Kisqali within the Medicare segment because there'll be prior authorization, step edits within Medicare prior to gaining access to Kisqali? And do you see any risk of spillover of that, assuming that thesis is correct, to the commercial book of business?

關於 IRA 對災難性保險的影響以及 PBM 和管理式醫療的負擔的問題。 Kisqali 的很大一部分通過醫療保險渠道。 Ibrance 似乎可以在通用化後以低得多的價格獲得。在多大程度上 - 對不起，您是否看到醫療保險領域內的 Kisqali 價格通縮，因為在獲得 Kisqali 訪問權之前，醫療保險內部會有事先授權和步驟編輯？假設論文是正確的，您是否看到任何溢出到商業商業賬簿的風險？

That's a good question, Andrew. I think in general I'd say we're doing a lot of scenario planning on how the IRA could impact various brands. And I think certainly on our minds is how the increased exposure of PBMs in the catastrophic, how that will get transferred or translated into actions against some of our medicines. I think the key for us to differentiate versus a generic in a class, like in the CDK4/6, will be having a broader indication -- set of indications relative to the existing medicine.

這是個好問題，安德魯。我認為總的來說，我會說我們正在做很多關於 IRA 如何影響各種品牌的情景規劃。我認為我們當然會想到 PBM 在災難性事件中的暴露程度如何增加，這將如何轉移或轉化為針對我們的某些藥物的行動。我認為我們區分一個類中的仿製藥的關鍵，比如在 CDK4/6 中，將有一個更廣泛的適應症——相對於現有藥物的一組適應症。

So I think that's going to be absolutely critical for us in this class to hopefully have the opportunity to expand into, as I mentioned earlier, stage IIa, stage IIb and stage III patients. Otherwise, I think there could certainly be spillover from -- in the metastatic setting if there aren't broad indications for the other 2 players. So we'll have to see how this plays out.

所以我認為這對於我們這個班的學生來說絕對至關重要，希望有機會擴展到，正如我之前提到的，IIa 期、IIb 期和 III 期患者。否則，如果其他 2 名球員沒有廣泛的跡象，我認為肯定會在轉移性環境中產生溢出效應。所以我們必須看看它是如何發揮作用的。

I would also say, in general, in some of these cancer classes, such as the CDK4/6, you do see contracting and you do see the opportunity for commercial insurers to get rebates from branded products. So that would be the, I think, tension there in the system, is they would have to give up their commercial rebates to potentially utilize the generic. So we'll have to see ultimately how all of this plays out. Thank you, Andrew.

我還要說，一般而言，在其中一些癌症類別中，例如 CDK4/6，您確實看到了合同，並且您確實看到了商業保險公司從品牌產品中獲得回扣的機會。因此，我認為，這將是系統中的緊張局勢，他們將不得不放棄商業回扣以潛在地利用仿製藥。所以我們必須看看這一切最終會如何發展。謝謝你，安德魯。

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

您的下一個問題來自 Jefferies 的 Peter Welford。

I just wanted to return to Pluvicto. I wonder if you could give us any more color at all in the centers that are currently using it. Are these generally academic centers? Are these generally centers that are using via the radiation oncologist? Or is it more nuclear medicine physicians? And particularly with regards to then the diagnostic. Just wondering, is it largely use your own [Locomet]? Or are you seeing use of other diagnostics before treatment? And is that potentially a source of revenue for you in the future, the diagnostics? Or should we think of this as largely a wash for Novartis as the focus has been he therapy?

我只是想回到 Pluvicto。我想知道您是否可以在當前使用它的中心為我們提供更多顏色。這些通常是學術中心嗎？這些通常是通過放射腫瘤學家使用的中心嗎？還是更多的核醫學醫師？尤其是關於當時的診斷。只是想知道，它主要使用您自己的[Locomet]嗎？或者您是否在治療前看到使用其他診斷方法？診斷是不是你未來的潛在收入來源？還是我們應該認為這在很大程度上是對諾華的洗禮，因為他的重點是治療？

Yes. Thanks, Peter. Overall, I'd say it's a mix. You have high academic centers. You also have large-scale centers, which are, in the case of prostate cancer, a combination of urology and nuclear medicine working in conjunction with medical oncology. We see that in some very large centers. And then we also see some nuclear radiology as well. That's -- and we generally are focused right now on larger volume centers in this first phase of launch.

是的。謝謝，彼得。總的來說，我會說這是一個混合體。你有很高的學術中心。您還擁有大型中心，就前列腺癌而言，這些中心是泌尿科和核醫學與醫學腫瘤學的結合。我們在一些非常大的中心看到了這一點。然後我們也看到了一些核放射學。那是 - 我們現在通常在第一階段的發布中專注於更大容量的中心。

I would note that if we were able to open it up even further in terms of the number of centers, we would expect even higher volumes for this medicine given the overall demand that we're seeing. But we're taking it stepwise, making sure we can service this first level of centers absolutely fully. And now we're in the process of adding additional centers step by step.

我要指出，如果我們能夠在中心數量方面進一步開放，鑑於我們看到的總體需求，我們預計這種藥物的銷量會更高。但我們正在逐步採取措施，確保我們可以完全為第一級中心提供服務。現在我們正在逐步增加更多的中心。

So it's a very different situation than with Lutathera, where because of the lower volumes and also neuroendocrine tumors being treated by certain specialists, there's a very relatively limited number of centers that were interested. Whereas here, we have more demand from centers, and then within the centers we're in very high demand that we're seeing at the moment. So those are all the dynamics we're seeing.

所以這是一個與 Lutathera 非常不同的情況，因為 Lutathera 的數量較少，而且某些專家正在治療神經內分泌腫瘤，因此感興趣的中心數量相對有限。而在這裡，我們對中心有更多的需求，然後在中心內，我們目前看到的需求非常高。所以這些就是我們看到的所有動態。

Overall, I would say, from a diagnostic standpoint, there is, of course, a preference for gallium, though we do see other PET ligands also used. We wouldn't view our [Locomet's] business as a driver for Novartis or something that can materially impact. It's kind of -- as you said, kind of a wash, it's much more about identifying patients.

總的來說，我想說，從診斷的角度來看，當然，人們更喜歡鎵，儘管我們確實看到其他 PET 配體也被使用。我們不會將我們 [Locomet 的] 業務視為諾華的驅動力或可以產生重大影響的事物。這有點像你說的，有點像洗頭，更多的是關於識別病人。

One of the dynamics, however, that's very important to understand, as you think about Pluvicto in across all lines of metastatic prostate cancer with the PSMAfore study that still needs to read out, is the broadening use of PET imaging for identifying patients who have an elevated PSA and to determine the extent of the metastases for their cancer. That is a dynamic that works very much in the favor of Pluvicto because if you identify these patients through the PET ligand, you're more likely to use a radioligand because you've seen the tumor and now you know the therapy can target what you see. And that, I think, is an important dynamic for the brand in the longer run.

然而，當您在 PSMAfore 研究中考慮 Pluvicto 在所有轉移性前列腺癌中的應用時，了解其中一個非常重要的動態是擴大使用 PET 成像來識別患有前列腺癌的患者。 PSA升高並確定其癌症的轉移程度。這是一個非常有利於 Pluvicto 的動態，因為如果您通過 PET 配體識別這些患者，您更有可能使用放射性配體，因為您已經看到了腫瘤並且現在您知道該療法可以針對您的目標看。我認為，從長遠來看，這對品牌來說是一個重要的動力。

Please switch to the backup feeds. Please continue to standby, your conference will resume shortly.

請切換到備用供稿。請繼續待機，您的會議將很快恢復。

(technical difficulty)

（技術難度）

Hello again. You are now live again.

再一次問好。你現在又活了。

Yes, sorry, I don't know what's going on today.

是的，對不起，我不知道今天發生了什麼。

Your next question comes from the line of Wimal Kapadia from Bernstein.

您的下一個問題來自 Bernstein 的 Wimal Kapadia。

Great. Thank you for the second question. Vas, you mentioned oral being quite important for Iptacopan. So I'm just curious how you think about the issue of adherence with an oral therapy in the real world setting. And then maybe you could talk here about the potential for breakthrough hemolysis as a result of potentially lower adherence.

偉大的。謝謝你的第二個問題。 Vas，您提到口語對 Iptacopan 非常重要。所以我只是好奇你如何看待在現實世界中堅持口服治療的問題。然後也許你可以在這裡談論由於潛在的較低依從性而導致突破性溶血的可能性。

Yes. Thanks, Wimal. I mean I think there's a couple of topics that we'll have to work through. So there's always the risk of compliance and how we manage that. We can certainly share as we have more data the experience we have in clinical -- in the controlled clinical trial setting. And as I mentioned earlier, we're confident in the profile we see with respect to breakthrough hemolysis.

是的。謝謝，維馬爾。我的意思是，我認為我們必須解決幾個主題。因此，始終存在合規風險以及我們如何管理該風險。隨著我們擁有更多數據，我們當然可以分享我們在臨床方面的經驗——在受控臨床試驗環境中。正如我之前提到的，我們對我們看到的突破性溶血情況充滿信心。

I think for many patients, having either regular infusions, weekly infusions, biweekly, subcu infusions, all these are quite burdensome. And at least our experience has been in severe diseases that patients are highly compliant with their oral therapies given that they know these are absolutely critical for their health and well-being.

我認為對於許多患者來說，要么定期輸液，要么每週輸液，要么每兩週輸一次，再輸一次，所有這些都是相當繁重的。至少我們的經驗是，患者對口服治療的依從性很高，因為他們知道這些對他們的健康和福祉至關重要。

So we believe that the compliance topic can be handled in an ultrarare population that is extremely well informed about their condition, and of course, we'll take the steps necessary. And that the benefits of what we believe and hope the clinical trial data will ultimately bear out, is improved efficacy, improved safety, improved overall control, improved secondary endpoints to be highlighted in the upcoming disclosures, will motivate patients to want to get on the best therapy for the management of their disease. And that's, I think, the case we'll have to make.

因此，我們相信合規主題可以在非常了解其狀況的極少數人群中處理，當然，我們將採取必要的步驟。我們相信並希望臨床試驗數據最終證實的好處是提高療效、提高安全性、改進整體控制、改進次要終點，這些將在即將發布的披露中突出顯示，這將激勵患者想要加入治療其疾病的最佳療法。我認為，這就是我們必須提出的情況。

Alongside that, of course, comes up the question on if you're competing against Part B medicines, how will that impact? Our assessment is that, in general, most of the hematologists who use this medicine are very low volume with respect to given that there's only 4,000 to 6,000 patients in the U.S. And that can be managed given that this is likely not a large cost recovery driver for those physicians.

當然，除此之外，如果您要與 B 部分藥物競爭，這將產生什麼影響？我們的評估是，總的來說，鑑於美國祇有 4,000 到 6,000 名患者，大多數使用這種藥物的血液學家的數量都非常少。鑑於這可能不是一個很大的成本回收驅動因素，這可以管理對於那些醫生。

Outside of the U.S., we would expect our ability to use an oral therapy to reduce the burden on health care systems as well as hopefully reach many of the patients who can't afford the currently approved therapies would allow us to, again, treat the majority, I hope, the majority of patients with these complement-driven diseases, including [TNH], over time.

在美國以外，我們希望我們能夠使用口服療法來減輕醫療保健系統的負擔，並希望能夠惠及許多無法負擔目前批准的療法的患者，這將使我們能夠再次治療大多數，我希望，隨著時間的推移，大多數患有這些補體驅動疾病的患者，包括 [TNH]。

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

您的下一個問題來自美國銀行的 Graham Parry。

So just following up again on Pluvicto, just to reiterate on Steve's point. So are you at capacity now though in Q3? Or should fourth quarter be higher than third quarter before you bring on next level of supply? And then in the pre-taxane setting, can you help us understand the proportion of patients in that first-line metastatic indication that goes through a large center, such as the ones you're targeting at the moment, versus community oncology and community urology centers?

所以只是再次跟進 Pluvicto，只是為了重申史蒂夫的觀點。那麼你現在在第三季度滿負荷嗎？或者在您帶來下一個供應水平之前，第四季度是否應該高於第三季度？然後在紫杉烷前環境中，您能否幫助我們了解通過大型中心（例如您目前針對的那些）的一線轉移適應症與社區腫瘤學和社區泌尿科的患者比例中心？

And on that last group, how do you stop them from just using taxane upfront anyway? Because if they refer a patient, they'll essentially lose the income from that patient, at least for the treatment portion of the disease. And then just lastly, a question we've had a few times this morning, just why the conservatism in the guidance if Innovative Medicines is growing mid- to high-single digits and Sandoz also now growing? You've upgraded Sandoz twice now without upgrading the group guidance. So just what's sort of the difference, the bridge between IM, mid- to high, and then group guidance (inaudible).

在最後一組，你如何阻止他們只是預先使用紫杉烷？因為如果他們轉診病人，他們基本上會失去該病人的收入，至少對於疾病的治療部分。最後，我們今天早上已經多次提出一個問題，如果創新藥物正在增長中高個位數，而山德士現在也在增長，為什麼指南中的保守主義？您現在已經升級了 Sandoz 兩次，而沒有升級組指導。那麼究竟有什麼區別，IM 之間的橋樑，中到高，然後是小組指導（聽不清）。

Yes. Thanks, Graham. First, on supply, to reiterate, we have adequate supply to meet the demand for the post-taxane vision population for Pluvicto. We see very high levels of demand, and we expect continued growth of the brand in the coming quarters, in that third, fourth line -- third, fourth line setting. And we allocate all capacity that is available in our network to the United States launch. If anything, we'll -- if we needed, we would prioritize launches in other markets to assume that the -- to ensure that the U.S. is at full demand.

是的。謝謝，格雷厄姆。首先，在供應方面，重申一下，我們有足夠的供應來滿足 Pluvicto 對紫杉烷後視力人群的需求。我們看到了非常高的需求水平，我們預計該品牌在未來幾個季度將在第三、四線——第三、四線設置中繼續增長。我們將網絡中可用的所有容量分配給美國的發射。如果有的話，我們會——如果需要，我們會優先考慮在其他市場推出產品，以確保美國的需求充足。

I guess what I was trying to indicate is we -- even with respect to the higher demand and higher volumes we expect to see in quarter 4, those volumes could be even higher if we were to completely unconstrain the number of centers that would want to bring this medicine on board. So all on the right trajectory.

我想我想表明的是我們——即使我們預計在第 4 季度看到更高的需求和更高的銷量，如果我們完全不限制想要的中心數量，這些銷量可能會更高。把這種藥帶上飛機。所以一切都在正確的軌道上。

With respect to the pre-taxane setting, we would roughly expect the new data, if positive, to triple, to quadruple the number of patients that would be eligible for -- so basically the broad range of patients in the metastatic setting, first, second, third line, but the full range of metastatic prostate cancer patients who have the key constrainer who have a PET scan. So once they have a PET scan, we would expect them to be eligible for our medicine. I think it's much more of PET scan availability that will drive a lot of the movement towards radioligand therapy perhaps versus taxanes or other available therapeutics.

關於紫杉烷前環境，我們粗略地預計，如果新數據為陽性，將增加三倍，使符合條件的患者數量增加四倍——所以基本上是轉移性環境中的廣泛患者，首先，二、三線，但全系列轉移性前列腺癌患者有關鍵制約者，有PET掃描。因此，一旦他們進行了 PET 掃描，我們希望他們有資格獲得我們的藥物。我認為，與紫杉烷類或其他可用療法相比，更多的是 PET 掃描的可用性將推動放射配體療法的發展。

And I guess what I'd say is it's really going to be in terms of referral patterns from community oncology to larger centers. Two dynamics there. One, how fast can we move out, because we believe that if we get to 400 or so centers, we can cover the full range of the population, the acceptability would be there. And then second, the quality of the data, so that physicians feel compelled to refer even if there's a risk that the patient has moved to another center. I think, in general, oncologists want what's best for their patients in all cases. And so I think that's going to be the other part of the story.

而且我想我想說的是，這實際上將是從社區腫瘤學到更大的中心的轉診模式。有兩種動力。一，我們能以多快的速度搬出，因為我們相信，如果我們到達 400 個左右的中心，我們可以覆蓋全範圍的人口，可接受性就會在那裡。其次，數據的質量，即使患者有轉移到另一個中心的風險，醫生也會感到有必要進行轉診。我認為，總的來說，腫瘤學家希望在所有情況下都對他們的患者最好。所以我認為這將是故事的另一部分。

For more specific data, let us come back to you. We have to probably do some more work in terms of the specifics of community oncology versus large-scale centers and where the patients are in that broad metastatic population.

如需更具體的數據，請讓我們回复您。在社區腫瘤學與大型中心的具體情況以及患者在廣泛的轉移人群中的位置方面，我們可能需要做更多的工作。

In terms of the guidance, Harry?

在指導方面，Harry?

Graham, I was expecting that question, of course. But I would say we are guiding for the total company mid-single-digit, top line and bottom line on our core sales and core [bank]. We have delivered on the company for the first 9 months 5% and 6%. And I expect, without getting into a very detailed quarter 4 guidance, that we are roughly in that range again in quarter 4. But of course, you have to take into account that U.S. Gilenya now has a generic entry, so maybe the top line a little bit less than the year-to-date, but a good mid- to high single digit on the bottom line. So overall, I think you see on the first 9 months that we are very much on track for the guidance. If it's a little bit stronger on the bottom line, so be it. But I think it is roughly in line with what you have seen so far.

格雷厄姆，我當然期待這個問題。但我想說，我們正在指導整個公司在我們的核心銷售和核心 [銀行] 上處於中個位數、頂線和底線。我們在前 9 個月向公司交付了 5% 和 6%。而且我預計，在沒有進入非常詳細的第 4 季度指導的情況下，我們在第 4 季度再次大致處於該範圍內。但當然，你必須考慮到美國 Gilenya 現在有一個通用條目，所以也許是頂線比年初至今略少，但在底線上是一個很好的中高個位數。所以總的來說，我認為你在前 9 個月看到我們在指導方面非常順利。如果它的底線更強一點，那就這樣吧。但我認為這與你目前所看到的大致一致。

Thanks, Graham.

謝謝，格雷厄姆。

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

您的下一個問題來自瑞士信貸的 Matthew Weston。

It's a simple question for Harry on tax. Obviously, you've changed guidance for full year '22 with a reduced tax rate and you highlighted the change in geographic mix. Harry, I wondered if that new lower tax rate is the best indication for 2023 or whether or not you see any meaningful changes that mean it's not a good indicator for the midterm?

對哈利來說，這是一個關於稅收的簡單問題。顯然，您更改了 22 年全年的指導並降低了稅率，並強調了地理組合的變化。哈利，我想知道新的較低稅率是否是 2023 年的最佳指標，或者您是否看到任何有意義的變化，這意味著它不是一個好的中期指標？

Yes. Thank you, Matthew. So overall, there is always a bit of volatility on geographic profit mix. Then we adjust, if you will, to each quarter to what we believe is our full year estimate on the core and reported taxes. So basically, we moved our full year estimate from 16.9%, as we had in the first 6 months, to 16.5%. Now I would -- again, we give detailed guidance, of course, for '23 then when we have our full year results in January or early February actually. And then -- but I would expect the tax rate to be in that range of 16.5% to 17.5%. We will update you with that than early February.

是的。謝謝你，馬修。因此，總體而言，地域利潤組合總是存在一些波動。然後，如果您願意，我們會調整每個季度，以我們認為是我們對核心稅和報告稅的全年估計。因此，基本上，我們將全年預期從前 6 個月的 16.9% 上調至 16.5%。現在我會 - 當然，我們會提供詳細的指導，當然，當我們在 1 月或 2 月初獲得全年業績時。然後 - 但我預計稅率將在 16.5% 至 17.5% 的範圍內。我們將在 2 月初之前向您更新。

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

您的下一個問題來自貝倫貝格的 Kerry Holford。

A follow-up question on Pluvicto. Just looking at Slide 33, it highlights a change to your approach in the non-metastatic setting. So could you confirm why you're now moving to start Phase II next year rather than a Phase III this year? Can you just clarify those changes and perhaps the opportunity in that setting as well, please?

關於 Pluvicto 的後續問題。只看幻燈片 33，它突出了您在非轉移性環境中方法的變化。那麼你能確認一下為什麼你現在要在明年開始第二階段而不是今年的第三階段嗎？你能澄清一下這些變化，也許還有那個環境中的機會，好嗎？

Yes. Thanks, Kerry. In the non-metastatic setting, the way our previous study was designed and based on feedback from the various investigators and the FDA, we believe the PSMAfore study covers the population that we had previously believed we needed to do an additional study for. So we redesigned our program to generate additional data in a different -- I don't have the detail at hand, but a different population within the non-metastatic setting. I would also say we're evaluating now Pluvicto as well in earlier lines of therapy to see if we can delay progression as well as evaluating combination therapies as well given the overall interest we've seen on the medicine and the clinical profile that we're seeing. So that's the reason we made that switch, based on the understanding from the regulators and experts in the United States.

是的。謝謝，克里。在非轉移性環境中，我們之前研究的設計方式以及基於各種研究人員和 FDA 的反饋，我們相信 PSMAfore 研究涵蓋了我們之前認為需要進行額外研究的人群。所以我們重新設計了我們的程序以在不同的環境中生成額外的數據——我手頭沒有詳細信息，但在非轉移性環境中是不同的人群。我還要說，我們現在正在評估 Pluvicto 以及早期治療線，看看我們是否可以延緩進展以及評估聯合療法以及考慮到我們對藥物和臨床概況的整體興趣。重看。這就是我們根據美國監管機構和專家的理解做出這種轉變的原因。

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

您的下一個問題來自摩根大通的 Richard Vosser。

When I look at the latest prescriptions for Tafinlar and Mekinist, they seem to have gone more into a decline in Q4. Is there anything that we should think about in terms of the dynamics you're seeing in the melanoma market, perhaps likely approval impacting those 2 brands that we should not think of the strong growth we've seen thus far continuing beyond for the brand?

當我查看 Tafinlar 和 Mekinist 的最新處方時，它們似乎在第四季度出現了更多的下降。就您在黑色素瘤市場中看到的動態而言，我們是否應該考慮任何事情，也許批准會影響這兩個品牌，我們不應該考慮迄今為止我們看到的強勁增長繼續超越該品牌？

Yes. Thanks, Richard. I mean, overall, I think we didn't note any significant change, at least wasn't flagged to us any significant competitive issues with respect to Taf-Mek in the U.S. or in our other key markets. But I think it's a good question and let us do some homework and get back to you. I don't think we have the answers straight in hand.

是的。謝謝，理查德。我的意思是，總的來說，我認為我們沒有註意到任何重大變化，至少在美國或我們其他主要市場上沒有向我們標記任何關於 Taf-Mek 的重大競爭問題。但我認為這是一個很好的問題，讓我們做一些功課，然後回复你。我認為我們沒有直接的答案。

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

您的下一個問題來自摩根士丹利的 Mark Purcell。

Vas, could you help us understand the scope of the free trial offer on Leqvio when it comes to patient initiation and what -- and how that might influence increase in ACP adoption? And then secondly, on the interest of LOE in China, what's the latest situation there in terms of your best guess?

Vas，您能否幫助我們了解 Leqvio 免費試用優惠的範圍，涉及到患者啟動以及什麼 - 以及這可能如何影響 ACP 採用率的增加？其次，關於LOE在中國的利益，您的最佳猜測是什麼？

So on the free trial offer, Mark, really, the idea was to -- while we already provide payment terms that allow physicians to stock doses and have time to get reimbursed before they would have to ultimately pay for the doses, we also noted that for some physicians, there was a need to provide an alternative option to get them comfortable to start, to stop the medicine. So in July, we rolled out a free trial offer program that provides a dose -- first dose for a patient free and then -- so the physician can get comfortable, use those doses and then hopefully then pull through to follow, keep the patient on therapy as they also get comfortable with the buy and bill process.

所以關於免費試用優惠，馬克，真的，這個想法是——雖然我們已經提供了付款條款，允許醫生儲存劑量並有時間在他們最終不得不支付劑量之前獲得報銷，但我們還注意到對於一些醫生來說，需要提供一種替代選擇，讓他們在開始用藥時感到舒適，然後停止用藥。所以在 7 月，我們推出了一項免費試用計劃，該計劃提供一劑 - 第一次免費為患者服用，然後 - 這樣醫生就可以感到舒服，使用這些劑量，然後希望能夠繼續跟進，留住病人接受治療，因為他們也對購買和賬單流程感到滿意。

We've had a very strong uptake of that program. And so I think over 1,000 physicians plus have signed up for the free trial offer program at the last look, which was still a month ago. So that's been a very positive step, I think, to get more physicians to stock Leqvio in the offices so that ultimately they can provide it to patients and then hopefully get more comfortable with an ongoing procedure to start the medicine, provide the medicine and get reimbursement.

我們對該計劃的接受度非常高。因此，我認為在最後一次查看時，已有超過 1,000 名醫生註冊了免費試用優惠計劃，那是一個月前的事了。所以我認為這是一個非常積極的步驟，讓更多的醫生在辦公室儲存 Leqvio，以便最終他們可以將它提供給患者，然後希望對正在進行的啟動藥物、提供藥物並獲得報銷。

Now with respect to Entresto in China, we currently are continuing our discussions with the -- our, I guess, our litigations with the -- in China against the various generics. I mean at this point in time, we would expect Entresto to be fully on -- protected through '23 and '24 and then impacts in '25 and beyond. But that's something we'll have to continue to look at because it's an evolving landscape with respect to data protection and the ongoing litigations that we have in the country. So we'll keep you updated accordingly.

現在關於 Entresto 在中國，我們目前正在繼續討論——我猜，我們與中國的訴訟——針對各種仿製藥。我的意思是，在這個時間點上，我們預計 Entresto 將完全開啟——在 23 年和 24 年受到保護，然後在 25 年及以後產生影響。但這是我們必須繼續關注的事情，因為在數據保護和我們在該國正在進行的訴訟方面，這是一個不斷發展的格局。因此，我們會為您提供相應的更新。

And I believe with that, we've cleared the entire question queue. I want to thank everyone, and apologies for the 2 technical disruptions. And we'll look forward to keep you up to date over the course of the remainder of this year.

我相信，我們已經清除了整個問題隊列。我要感謝大家，並對兩次技術中斷表示歉意。我們期待在今年剩下的時間里為您提供最新信息。

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

謝謝你。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。