Novartis AG (NVS) 2023 Q3 法說會逐字稿

Good morning, and good afternoon, and welcome to the Novartis Q3 2023 Results Release Conference Call and Live Webcast. (Operator Instructions) The conference is being recorded. (Operator Instructions) A recording of the conference call, including the Q&A session, will be available on our website shortly after the call ends.

早上好，下午好，歡迎來到諾華 2023 年第三季業績發布電話會議和網路直播。 （操作員指示）會議正在錄音。 （操作員說明）電話會議的錄音（包括問答環節）將在通話結束後不久在我們的網站上提供。

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

接下來，我想將會議交給投資者關係全球主管 Samir Shah 先生。請繼續，先生。

Thank you very much, everybody, for joining once again. Just before we start, I'll just read you the safe harbor statement. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause 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.

非常感謝大家再次加入。在我們開始之前，我將向您宣讀安全港聲明。今天提供的資訊包含前瞻性陳述，涉及已知和未知的風險、不確定性和其他因素。這些可能導致實際結果與此類陳述明示或暗示的任何未來結果、績效或成就有重大差異。有關其中一些因素的說明，請參閱該公司的 20-F 表格以及 6-K 表格中的最新季度業績，該表格分別已提交給美國證券交易委員會。

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

這樣，我就把電話轉給瓦斯。

Thank you, Samir, and thanks, everyone, for joining today's conference call. As you saw, we had some really strong results. But I wanted to also take a step back and note that this is an important moment for the company after many years of focusing the organization to become a pure-play medicines company. With the spin of Sandoz, we've completed that multiyear journey.

謝謝薩米爾，也謝謝大家參加今天的電話會議。正如您所看到的，我們取得了一些非常出色的成果。但我也想退一步指出，在公司多年來專注於成為純粹的藥品公司之後，這是一個重要的時刻。隨著山德士的推動，我們完成了多年的旅程。

Along the way, we've been able to create multiple important companies for the world in consumer health and eye care devices and now Sandoz in generics, alongside exiting our Roche stake and taking a number of shareholder-friendly actions, which we'll talk more about on the call. But I think this quarter demonstrates that Novartis is well positioned as a pure-play innovative medicines company to consistently drive top and bottom line growth for the years to come.

一路走來，我們已經能夠在消費者健康和眼保健設備領域為世界創建多家重要的公司，現在又在仿製藥領域創建了山德士，同時我們還退出了羅氏股份，並採取了一些有利於股東的行動，我們將討論這些行動有關通話的更多資訊。但我認為本季顯示諾華作為一家純粹的創新藥物公司處於有利地位，能夠在未來幾年持續推動營收和利潤的成長。

So coming to the first slide. As you saw earlier this morning, we delivered strong sales growth, margin expansion, and we were able to raise our guidance for the third time this year, along with the successful spin of Sandoz. Sales grew 12% and core operating income grows up 21% on the quarter. On the 9 months, sales were up 10%, core operating income grow 19%, all in constant currencies. And this allowed us to raise our guidance, which Harry will go through in more detail.

現在來看第一張投影片。正如您今天早上早些時候看到的，我們實現了強勁的銷售成長和利潤擴張，隨著山德士的成功轉型，我們今年第三次提高了我們的指導。本季銷售額成長 12%，核心營業收入成長 21%。前 9 個月，銷售額成長 10%，核心營業收入成長 19%（全部以固定匯率計算）。這使我們能夠提高我們的指導，哈利將更詳細地介紹這一點。

We also had a number of important innovation milestones, and I know many of you were on the call earlier with respect to Pluvicto's data presentation at ESMO as well as other results and milestones over the course of the quarter, which I'll go through the presentation.

我們還有許多重要的創新里程碑，我知道你們中的許多人早些時候都參加了電話會議，了解 Pluvicto 在 ESMO 上的數據演示以及本季度的其他結果和里程碑，我將詳細介紹這些推介會。

Now moving to Slide 5. That growth that you saw was driven by our key growth drivers and really a broad-based performance across the company, which I think is reflecting the focus that we have in the organization now on 4 key TAs, 9 key brands, a simplified organization and really a focus on execution. This portfolio grew 41% in constant currencies, and we expect that growth to continue. We also saw the normalization of health care systems in many of our key markets, which also buoyed many of our established brands and older patented brands.

現在轉到幻燈片 5。您看到的成長是由我們的關鍵成長動力以及整個公司的廣泛績效推動的，我認為這反映了我們現在在組織中對 4 個關鍵 TA、9 個關鍵 TA 的關注品牌、簡化的組織、真正注重執行力。以固定匯率計算，該投資組合成長了 41%，我們預計這種成長將持續下去。我們也看到許多關鍵市場的醫療保健系統正常化，這也提振了我們許多知名的品牌和較早的專利品牌。

Now moving to Slide 6. In going through each brand in turn, starting with Entresto. Entresto delivered 31% growth on the quarter, reaching $1.5 billion. That growth was driven by performance both in the U.S. and in the ex-U.S. market. You can see in the center panel, our weekly TRx in the U.S. continues to reach new highs every week.

現在轉到投影片 6。依序瀏覽每個品牌，從 Entresto 開始。 Entresto 本季成長 31%，達到 15 億美元。這一增長是由美國和美國以外地區的業績推動的。市場。您可以在中間面板中看到，我們在美國的每週 TRx 每週都繼續創下新高。

With respect to some more of the details, the U.S. growth was driven by 28% -- U.S. at 28% constant currency growth, 1.4 million TRxs in the quarter. Ex-U.S. sales were up 34%, and I think importantly, we're seeing strong performance in China and Japan from the hypertension indications that we've been able to achieve in these 2 markets.

至於更多細節，美國的成長是由 28% 推動的——美國以 28% 的恆定匯率成長，本季有 140 萬個 TRx。前美國銷售額成長了 34%，我認為重要的是，我們在中國和日本的高血壓適應症方面看到了強勁的表現，我們已經在這兩個市場實現了這一目標。

Importantly, in Japan, we have protection for Entresto out into the early 2030s. So we're confident in the continued growth of this medicine. We have a strong guidelines position in the U.S. and the EU. We expect further penetration in heart failure and hypertension. As a reminder, our pediatric approval in EU confirms our RDP to November 2026. And we continue to prosecute our appeal in the U.S. to the recent patent rulings as well as filed to uphold our existing patents, and we continue to guide to a mid-2025 loss of exclusivity in the U.S. as we continue to prosecute that patent portfolio.

重要的是，在日本，我們對 Entresto 提供保護直至 2030 年代初期。因此，我們對這種藥物的持續增長充滿信心。我們在美國和歐盟擁有強而有力的指導地位。我們預計在心臟衰竭和高血壓領域將進一步滲透。提醒一下，我們在歐盟的兒科批准確認了我們的 RDP 將於 2026 年 11 月生效。我們將繼續在美國對最近的專利裁決提出上訴，並提出維持我們現有專利的請求，我們將繼續指導中期隨著我們繼續起訴該專利組合，到2025 年將失去在美國的獨佔性。

We have no generics approved to date by the FDA.

到目前為止，我們還沒有獲得 FDA 批准的仿製藥。

Moving to the next slide, Slide 7. Cosentyx returned to growth, and we expect a stronger quarter 4 as we start to lap some of the revenue adjustments that we had in the prior year. You can see this growth was driven both by a stabilization in the U.S. as well as strong performance outside the U.S. U.S. sales were down 3%. But when you adjust for the revenue adjustment items, they were broadly flat, supported by volume growth. And then ex-U.S. sales were up 15% as we were able to grow in each of our core indications. We expect stronger growth in quarter 4, continued volume growth, lower prior year base effects from the RD true-ups. In addition, in Europe, our hidradenitis suppurativa indication has been approved, and the launch is on track, and we're beginning to already see early signs of uptake from this new indication.

轉到下一張投影片，即投影片 7。Cosentyx 恢復成長，我們預計第四季將表現強勁，因為我們開始完成去年的一些收入調整。您可以看到，這一成長是由美國市場穩定以及美國以外地區的強勁表現推動的。美國銷售額下降了 3%。但當你調整收入調整項目時，在銷售成長的支撐下，它們基本上持平。然後是美國以外的地方由於我們能夠在每個核心適應症上成長，銷售額成長了 15%。我們預期第四季的成長將更加強勁，銷售量將持續成長，RD 調整帶來的上年基數效應將降低。此外，在歐洲，我們的化膿性汗腺炎適應症已獲得批准，並且上市已步入正軌，我們已經開始看到這一新適應症的早期跡象。

From a life cycle management standpoint, we've received approval in the U.S. for our IV formulation, which allows us now to bring this medicine to patients and providers who prefer to take advanced medicines for rheumatological indications in an IV setting. We're the first non-TNF so novel agent that's now approved with an IV formulation, and we look forward now to bring that medicine to those health care practitioners.

從生命週期管理的角度來看，我們的靜脈注射製劑已在美國獲得批准，這使我們現在可以將這種藥物帶給那些喜歡在靜脈注射環境中服用先進藥物治療風濕病適應症的患者和提供者。我們是第一個非腫瘤壞死因子如此新穎的藥物，現已批准採用靜脈注射製劑，我們現在期待將該藥物帶給那些醫療保健從業者。

In addition, we're on track for the hidradenitis approval in the U.S. in quarter 4. Three Phase III studies ongoing, giant cell arteritis, PMR and rotator cuff tendinopathies that also remain on track. So overall, solid performance for Cosentyx setting us up well for the coming years.

此外，我們預計在第四季度在美國批准汗腺炎治療。三項 III 期研究正在進行中，鉅細胞動脈炎、PMR 和肩袖肌腱病變也仍在按計劃進行。總的來說，Cosentyx 的穩健表現為我們未來幾年奠定了良好的基礎。

Moving to Slide 8. Kesimpta continued its strong launch trajectory across regions. We did have a onetime revenue adjustment in the EU, which accounted for some of this growth, but it's important to note that our underlying sales growth was still 86% for this brand. In the U.S., we're growing faster than the market. TRxs were up 75%, NBRxs were up 30%. And I would note that the B-cell NBRx share is still only 56% of the MS market, TRx is much lower, showing that the whole B-cell class has a long room to grow to get as many patients as possible with the most effective therapy.

轉到幻燈片 8。Kesimpta 繼續在各個地區保持強勁的發布軌跡。我們確實在歐盟進行了一次收入調整，這在一定程度上促成了這一增長，但值得注意的是，我們該品牌的基本銷售額增長仍然為 86%。在美國，我們的成長速度快於市場。 TRx 上漲 75%，NBRx 上漲 30%。我要指出的是，B 細胞NBRx 的份額仍然僅為MS 市場的56%，TRx 則低得多，這表明整個B 細胞類別還有很長的成長空間，以便為盡可能多的患者提供最優質的服務。有效的治療。

In Europe, we're seeing a solid launch momentum, 29,000 patients now treated. Most of those patients are naive or first switch. Our Q3 sales included that revenue deduction adjustment. And importantly, we're also seeing solid performance in Asia as well with this brand. So we're confident in the continued future growth of Kesimpta. Only about 1/3 of MS patients are on B cell therapies and will continue to drive that growth of the B-cell class as well as Cosentyx share within the B-cell class. We have NBRx leadership in multiple key markets such as Germany, and we have a compelling product profile that I think you know well, 1-minute-a-month dosing from home or anywhere, 5-year efficacy, strong safety and tolerability and a very attractive profile from a local adverse event profile when the medicine is given unlike the recently approved subcu IV formulation of a competitor product.

在歐洲，我們看到了強勁的啟動勢頭，現在已有 29,000 名患者接受治療。這些患者中的大多數是天真的或第一次轉換。我們第三季的銷售額包括收入扣除調整。重要的是，我們也看到該品牌在亞洲的穩健表現。因此，我們對 Kesimpta 未來的持續成長充滿信心。只有約 1/3 的 MS 患者接受 B 細胞治療，並將繼續推動 B 細胞類別以及 Cosentyx 在 B 細胞類別中所佔份額的成長。我們在德國等多個關鍵市場擁有NBRx 領導地位，我們擁有令人信服的產品概況，我想您很了解，每月1 分鐘在家或任何地方給藥，5 年療效，強大的安全性和耐受性以及與最近批准的競爭對手產品的 subcu IV 配方不同，給藥時的局部不良事件概況非常有吸引力。

Now moving to Slide 9. Kisqali sales grew 76% to $562 million in the quarter. And I think this is really a reflection of the increasing recognition of the differentiated benefit risk profile we have with this medicine. You can see the growth is broad-based across geographies on the left-hand panel. In the middle, our NBRx share has now reached 46%. Clear leadership from a metastatic breast cancer setting as we continue to gain in this setting based on the strong data that we show here on the right-hand panel data, you all know well. Three OS wins in MONALEESA-2, 7 and 3, NCCN guidelines supporting the use of the medicine. The Right Choice data, which recently showed a benefit versus doublet chemo in aggressive metastatic breast cancer. And of course, an adverse event profile that is increasingly understood and well managed by practitioners around the globe. So in the metastatic setting, we continue to believe Kisqali has a multibillion-dollar potential and is now demonstrating that with its strong growth.

現在轉到投影片 9。Kisqali 本季銷售額成長 76%，達到 5.62 億美元。我認為這確實反映了我們對這種藥物的差異化效益風險狀況的日益認識。您可以在左側面板上看到跨地區的廣泛增長。中間，我們的 NBRx 份額現在已經達到 46%。眾所周知，我們在右側面板數據上顯示的強有力的數據基礎上，在轉移性乳癌領域取得了明顯的領先地位，我們在這一領域繼續取得進展。三個 OS 在 MONALEESA-2、7 和 3 中獲勝，NCCN 指南支持該藥物的使用。 Right Choice 數據最近顯示，在侵襲性轉移性乳癌中，化療相對於雙藥化療具有益處。當然，全球從業人員越來越了解並妥善管理不良事件概況。因此，在轉移環境中，我們仍然相信 Kisqali 具有數十億美元的潛力，並且現在以其強勁的成長證明了這一點。

Now moving to the next slide. In the quarter, we also completed the Phase III NATALEE iDFS analysis with 500 events now complete and are on track for a submission in quarter 4. In addition, in quarter 3, we did submit in the EU. As a reminder, on the left-hand side of the panel, you see the data that we showed at ASCO, which demonstrated a consistent profile for Kisqali across all of the various subgroups that you see here listed as well as RFS and DDFS.

現在轉到下一張投影片。在本季度，我們還完成了第三階段 NATALEE iDFS 分析，現在已完成 500 個事件，並預計在第四季度提交。此外，在第三季度，我們確實在歐盟提交了。提醒一下，在面板的左側，您可以看到我們在 ASCO 上展示的數據，這些數據顯示了 Kisqali 在此處列出的所有各個子組以及 RFS 和 DDFS 中的一致概況。

At ESMO 2023, early this week, actually yesterday, we also put forward data that showed the consistent iDFS benefit across subgroups regardless of stage, menopausal status, age or nodal status, as well as a good tolerability profile for the medicine. So as mentioned, we filed in Europe, 500 iDFS event milestone reached. The data was consistent with what we've already seen at the ASCO data set and we will be presenting that data at an upcoming medical congress in quarter 4, and our U.S. submission is planned for quarter 4 as well.

在本周初（實際上是昨天）的ESMO 2023 上，我們也提出了數據，顯示無論階段、停經狀態、年齡或淋巴結狀態如何，各個亞組的iDFS 均具有一致的益處，以及藥物良好的耐受性。如前所述，我們在歐洲提交的 iDFS 活動達到了 500 個里程碑。這些數據與我們在 ASCO 數據集中看到的數據一致，我們將在第四季度即將召開的醫學大會上展示該數據，我們也計劃在第四季度向美國提交數據。

Now moving to the next slide. Now Pluvicto grew to $256 million. And it's important to note that our supply now is fully unconstrained as our Millburn facility is fully up and running with multiple lines approved. Our Indianapolis facility is now filed, and we're focused on initiating new patients.

現在轉到下一張投影片。現在 Pluvicto 的銷售額已增至 2.56 億美元。值得注意的是，我們的供應現在完全不受限制，因為我們的米爾本工廠已全面啟動並運行，多條生產線已獲得批准。我們印第安納波利斯的設施現已備案，我們的重點是接收新患者。

Now I wanted to say a word on the quarter-on-quarter growth that we saw with Pluvicto. It's important to note that for this medicine, it is provided in 6 doses, 6 weeks apart. So this is a 36-week medicine, so over 9 months. Earlier this year, when we experienced our supply disruption, we had 2 factors that impacted our sales in quarter 3 of this year. One, we had sicker patients being put on the therapy given that practitioners wanted to provide the therapy to the patients most in need. Many of these patients only completed 2 to 4 cycles of Pluvicto.

現在我想談談我們在 Pluvicto 上看到的季度環比增長。值得注意的是，該藥分 6 劑提供，間隔 6 週。所以這是一個 36 週的藥物，所以超過 9 個月。今年早些時候，當我們經歷供應中斷時，有兩個因素影響了今年第三季的銷售。第一，考慮到醫生希望為最需要的患者提供治療，我們讓病情較重的患者接受治療。其中許多患者僅完成 2 至 4 個週期的 Pluvicto。

Then separate from that, we also had much fewer patient starts through quarter 2, which limited the base of patients receiving Pluvicto for their third, fourth, fifth, sixth doses through quarter 3. Now what I would want to highlight is we're seeing 50% -- already 50% patient growth in quarter 3 over quarter 2, and we expect that growth to continue. We're seeing solid bookings into next year. So as we rebuild the base of patients that are ongoing on Pluvicto and adding new patients above, we would expect then growth to get back to where we expect it to be.

除此之外，到第二季度開始的患者數量也少得多，這限制了到第三季度接受第三、第四、第五、第六劑Pluvicto 的患者基數。現在我想強調的是，我們正在看到50%——第三季度的患者數量比第二季度已經增長了 50%，我們預計這種增長將持續下去。我們看到明年的預訂量很大。因此，當我們重建 Pluvicto 上正在進行的患者基礎並增加上述新患者時，我們預計成長將回到我們預期的水平。

We continue to be on track for around $1 billion of sales for this year for Pluvicto as we previously guided. And you can see here some of the other elements of the story, 200 active centers ordering in the U.S. and onboarding another 130 centers. Ex-U.S. reimbursement is continuing to progress well. And as I mentioned, our capacity is now unconstrained and we look forward to bringing online the Indianapolis site to really provide us enough capacity to fully meet the U.S. market. We're also in the process now of adding additional facilities in Asia as we prepare to launch the medicine across multiple geographies in the Asian landscape as well.

正如我們之前的指導，今年 Pluvicto 的銷售額仍有望達到 10 億美元左右。您可以在這裡看到故事的其他一些元素，200 個活躍的中心在美國訂購，並在另外 130 個中心入駐。前美國報銷工作持續進展順利。正如我所提到的，我們的產能現在不受限制，我們期待印第安納波利斯站點上線，真正為我們提供足夠的產能來完全滿足美國市場的需求。我們現在也在亞洲增加更多設施，準備在亞洲多個地區推出該藥物。

Now moving to the next slide, Slide 12. Now as you saw already with the presentation earlier today as well as at ESMO yesterday, the PSMA study -- PSMAfore study showed robust efficacy and favorable safety, and I won't go through all of the data again, so I believe many of you were on the call. But I think the data set is compelling. We believe that it had clearly demonstrated the benefit of this medicine. We presented it at ESMO, and there was, I think, a strong positive vibe. I was at the Congress myself and really felt like practitioners really excited about bringing this medicine to more patients. Our submission for FDA is now planned. Our current plan is to submit the medicine to FDA when we reach a 75% information fraction at OS because we believe that will provide us an adequate data set, both for crossover adjusted, unadjusted OS as well as all of the excellent data that you see on the slide.

現在轉到下一張投影片，即投影片12。正如您在今天早些時候的演示以及昨天在ESMO 上看到的那樣，PSMA 研究-- PSMAfore 研究顯示出強大的功效和良好的安全性，我不會詳細介紹所有這些再次提供數據，所以我相信你們中的許多人都參加了電話會議。但我認為數據集很有說服力。我們相信它已經清楚地證明了這種藥物的益處。我們在 ESMO 上展示了它，我認為當時有一種強烈的積極氛圍。我自己也參加了大會，我真的感到從業者對於將這種藥物帶給更多患者感到非常興奮。我們現在正在計劃向 F​​DA 提交申請。我們目前的計劃是，當 OS 資訊分數達到 75% 時，將藥物提交給 FDA，因為我們相信這將為我們提供足夠的數據集，包括交叉調整、未調整的 OS 以及您看到的所有優秀數據在幻燈片上。

Now moving to Slide 13. Scemblix sales grew across all regions, and I think that demonstrated the high unmet need for CML. Now a few things to note when you look at the Scemblix sales. While the sales reflected continued demand from patients for Philadelphia positive CML, CP-resistant or patients who are intolerant to 2 or more TKIs, really later-line therapy, and we continue to have a strong third line market share. We did also see a slowing of some of the patients with specific mutations that are indicated for Scemblix, which did lead to some of the slowdown as well as some revenue and inventory adjustments in the quarter.

現在轉到投影片 13。Scemblix 銷售額在所有地區都在成長，我認為這表明 CML 的需求尚未得到滿足。現在，當您查看 Scemblix 銷售情況時需要注意一些事項。雖然銷售反映了費城陽性 CML、CP 抗藥性患者或對 2 種或更多 TKI 不耐受的患者的持續需求，但我們仍然擁有強大的三線市場份額。我們確實也看到一些患有 Scemblix 特定突變的患者的治療速度放緩，這確實導致了一些放緩以及本季度的一些收入和庫存調整。

I think really now the key for Scemblix is to continue to drive strong growth in the third-line setting. But for the medicine to become a very significant part of our portfolio, what will be critical is moving into earlier line. We are on track for the readout of the preferred first-line registrational study in the first part of next year with a filing, if positive, expected in 2024, as well as Phase IV studies in the second-line setting as well. If those studies are positive, we do believe this medicine has the potential to be a multibillion-dollar medicine to continue to support Novartis growth and importantly, provides CML patients with an improved next-generation therapy following our legacy of Gleevec and Tasigna.

我認為現在 Scemblix 的關鍵是繼續推動三線領域的強勁成長。但要使該藥物成為我們產品組合中非常重要的一部分，至關重要的是進入早期產品線。我們預計在明年上半年公佈首選的第一線註冊研究，如果結果積極，預計將於 2024 年提交申請，此外還將進行二線治療的 IV 期研究。如果這些研究結果是正面的，我們確實相信這種藥物有潛力成為一種價值數十億美元的藥物，以繼續支持諾華的成長，更重要的是，繼我們的格列衛和塔西尼亞傳統之後，為CML 患者提供改進的下一代治療方法。

Now moving to Slide 14. Leqvio continued to expand steadily in the quarter as we've guided. This will be a long build as we continue to build out the buy-and-bill pathway and educate physicians. We think this performance benchmarks well versus other PCSK9 launches. And interestingly, also benchmarks well against other asymptomatic Part B therapies that have been launched over the last 2 decades. So I think we're on a solid trajectory, but this will be the long haul to get to the full potential multibillion-dollar potential for this medicine.

現在轉到投影片 14。Leqvio 按照我們的指導，在本季繼續穩步擴張。這將是一個長期的過程，因為我們將繼續建立購買和計費途徑並教育醫生。我們認為此效能基準與其他 PCSK9 發布產品相比表現良好。有趣的是，它與過去 20 年推出的其他無症狀 B 部分療法也有很好的基準。因此，我認為我們正走在堅實的軌道上，但要充分發揮這種藥物數十億美元的潛力，這將是一個漫長的過程。

Our adoption was now at 3,100 facilities, which is about 16% up from quarter 2, 55% of the business is now from buy and bill, and we continue to expand that. And our enablers for future growth really haven't changed. It's to drive depth in our key accounts. We know that once key accounts get up to 8 to 10 patients on Leqvio that really drives higher -- even higher utilization in those accounts. We need to continue to educate and expand buy and bill across the entire landscape of cardiology offices, and we're looking now to hyper target physician groups that we think are most likely to have urgency to treat patients with elevated risk following a cardiovascular event.

目前我們的採用率已達到 3,100 個設施，比第二季度增長了約 16%，現在 55% 的業務來自購買和計費，我們將繼續擴大這一規模。我們未來成長的推動因素確實沒有改變。這是為了提高我們關鍵客戶的深度。我們知道，一旦 Leqvio 的關鍵客戶達到 8 到 10 名患者，這些客戶的使用率就會真正提高，甚至更高。我們需要繼續在整個心臟病學辦公室中進行教育和擴大購買和計費，我們現在正在尋找我們認為最有可能緊急治療心血管事件後高風險患者的超級目標醫生群體。

Importantly as well, we have a rollout now with the medicine approved in China and Japan. And thus far, we are seeing strong early uptake in China and hopeful that we can expand that utilization with NRDL listing in the coming years in China as well.

同樣重要的是，我們現在已經推出了該藥物在中國和日本獲得批准的產品。到目前為止，我們看到中國的早期應用強勁，並希望未來幾年我們也能透過將其納入國家醫保目錄來擴大其在中國的使用。

Now moving to Slide 15. Now turning to the pipeline readouts in 2023. We've covered most of the Kisqali and Pluvicto milestones already. I would note as well that iptacopan, we'll cover the PNH as well as -- PNH, I should say that we're on track for the FDA and EMA, and those problems are continuing to be reviewed, and we're on track with those. The APPLAUSE-IgAN study, I'll go through in a few slides, and the APPEAR-rC3G Phase III readout remains on track as well for quarter 4. As well after our recent acquisition that we've closed for Chinook, our atrasentan readout for IgAN is also -- continues to be expected in quarter 4 of this year.

現在轉到幻燈片 15。現在轉到 2023 年的管道讀數。我們已經介紹了 Kisqali 和 Pluvicto 的大部分里程碑。我還要指出的是，iptacopan，我們將涵蓋 PNH 以及 - PNH，我應該說我們正在 FDA 和 EMA 的軌道上，這些問題正在繼續審查，我們正在努力跟踪那些。 APPLAUSE-IgAN 研究，我將在幾張投影片中介紹，而APPEAR-rC3G 第三階段讀數也將在第四季度保持在正軌上。在我們最近完成對Chinook 的收購之後，我們的atrasentan 讀數也保持在正軌上。 IgAN 預計將在今年第四季發布。

Now moving to Slide 16 and turning to our '24 to '25 time frame. I'll cover remibrutinib in a few slides. I've already mentioned that Scemblix remains on track. Our Pluvicto hormone-sensitive prostate cancer readout is also on track for 2024, and we continue to pursue Pluvicto in full range of earlier lines of prostate cancer therapy. I would note as well our OAV-101 SMA intrathecal study is now with a readout expected in '24, with the submission planned in 2025. Pelacarsen and ianalumab, all the studies also remain on track. And we have a number of additional indications for iptacopan, which you'll see in a few slides.

現在轉到投影片 16，並轉向我們的「24 至 25」時間範圍。我將在幾張投影片中介紹瑞米魯替尼。我已經提到 Scemblix 仍處於正軌。我們的 Pluvicto 荷爾蒙敏感型前列腺癌讀數也有望在 2024 年實現，我們將繼續在全系列早期前列腺癌治療中追求 Pluvicto。我還要指出的是，我們的 OAV-101 SMA 鞘內研究目前預計將於 24 年公佈結果，計劃於 2025 年提交。Pelacarsen 和 ianalumab，所有研究也仍在按計劃進行。我們還提供了 iptacopan 的許多其他適應症，您將在幾張幻燈片中看到。

Now moving to Slide 17. Now turning to remibrutinib, where we read out 2 studies in the quarter, both demonstrated consistent, clinically meaningful and statistically significant benefit in CSU. As a reminder, the REMIX 1 and 2 studies randomized 450 patients to remibrutinib or placebo with a primary endpoint at week 12. At week 24, patients on the placebo group rolled over on to remibrutinib for an additional follow-up out to 52 weeks, which then enabled for the final submission in that -- with the safety data collected during that open-label treatment period.

現在轉到投影片 17。現在轉到瑞米魯替尼，我們讀出了本季度的 2 項研究，兩項研究都證明了 CSU 具有一致的、具有臨床意義和統計顯著性的益處。提醒一下，REMIX 1 和2 研究將450 名患者隨機分配至瑞布替尼組或安慰劑組，並在第12 週達到主要終點。在第24 週，安慰劑組的患者轉而使用瑞布替尼組，進行為期52 週的額外追蹤。然後就可以最終提交在該開放標籤治療期間收集的安全數據。

Of note, all participants were on a stable and locally-label approved dose of a second-generation H1 antihistamine throughout the entire study. Remibrutinib met all primary and secondary endpoints at 12 weeks. There was a clinically meaningful and statistically significant reduction in urticaria activity. We saw a very fast symptom improvement as early as 2 weeks. The medicine was well tolerated, good safety profile, balanced liver function test, which I think is really critical for this class, and an oral medicine. And this allows us to bring remibrutinib forward. We hope, with a filing in 2024, the data will be fully presented at ACAAI in 2023. And all of us to bring this medicine for a well ahead of our multiple sclerosis readout. And we continue to also explore it now in other indications given the strength of the readout that we saw here, other autoimmune indications that could also be addressed by remibrutinib.

值得注意的是，在整個研究過程中，所有參與者都服用穩定且當地標籤核准劑量的第二代 H1 抗組織胺。瑞米布替尼在 12 週時達到了所有主要和次要終點。蕁麻疹活動性有臨床意義及統計學顯著性降低。早在兩週內我們就看到症狀改善速度非常快。該藥物耐受性良好，安全性良好，肝功能測試平衡，我認為這對於此類藥物非常重要，並且是口服藥物。這使我們能夠推進瑞米魯替尼的發展。我們希望，在 2024 年提交文件後，這些數據將在 2023 年的 ACAAI 上完整呈現。我們所有人都能在我們的多發性硬化症讀數之前儘早提供這種藥物。鑑於我們在這裡看到的讀數的強度，我們現在還在其他適應症中繼續探索它，其他自體免疫適應症也可以透過瑞米替尼解決。

Now moving to Slide 18. When you think about how we're going to position remibrutinib, it's an opportunity for an efficacious oral therapy with a fast onset of action in between the use of antihistamines and biologics. There is a CSU treatment gap. There's about 400,000 patients that are not controlled with standard of care. They have a high unmet need after antihistamines, and that's where we'd like to position this medicine. And given the data that we've seen with efficacy that is in the range of biologics, that gives us the opportunity, we believe, to position this medicine successfully in the future.

現在轉到投影片 18。當您考慮我們將如何定位瑞布替尼時，這是一個在使用抗組織胺和生物製劑之間快速起效的有效口服療法的機會。 CSU 存在治療差距。大約有 40 萬名患者沒有受到標準護理的控制。他們在抗組織胺之後有很高的未滿足需求，這就是我們想要定位這種藥物的地方。鑑於我們在生物製劑範圍內看到的療效數據，我們相信，這為我們提供了在未來成功定位這種藥物的機會。

Now moving to Slide 19. Iptacopan or oral selective factor B inhibitor, we read out the APPLAUD study. I think you all well know, we had positive data both in APPLY and APPOINT in PNH. That data is now filed. C3G is on track. We also have a who is have IC-MPGN as well as other Phase IIb and Phase III readouts that are ongoing, including lupus nephritis.

現在轉到投影片 19。Iptacopan 或口服選擇性因子 B 抑制劑，我們宣讀 APPLAUD 研究。我想你們都知道，我們在 PNH 的 APPLY 和 APPOINT 方面都有正面的數據。該資料現已歸檔。 C3G已步入正軌。我們還有 IC-MPGN 以及正在進行的其他 IIb 期和 III 期讀數，包括狼瘡性腎炎。

And so if you go to the next slide, I wanted to just say a word about the APPLAUSE study. Iptacopan the study demonstrated clinically meaningful, highly statistically significant proteinuria reduction in the study. For -- as a reminder, this is the study of biopsy confirmed patients with IgA nephropathy, who are at risk of progression. They had an elevated proteinuria of over 1 gram per gram despite stable background therapy. They were randomized 1:1 placebo to iptacopan.

因此，如果您轉到下一張投影片，我只想簡單介紹一下 APPLAUSE 研究。 Iptacopan 研究證明了具有臨床意義、高度統計顯著性的蛋白尿減少。提醒一下，這是對活檢證實患有 IgA 腎病的患者進行的研究，這些患者有進展的風險。儘管背景治療穩定，但他們的蛋白尿仍高於每克 1 克。他們按照 1:1 的比例隨機分配到 iptacopan 和 iptacopan。

This is the data from the interim analysis at 9 months, looking only at proteinuria. The end of study resolved once all patients are enrolled and are fallout fully would occur in 2025, and that would look at eGFR. The positive top line results at this interim analysis showed superiority versus placebo and proteinuria reduction, and this is on top of optimized supportive care. This result is clinically meaningful, highly statistically significant. I think very, very pleased with the results that we saw.

這是 9 個月時的中期分析數據，僅關注蛋白尿。一旦所有患者都入組並完全結束，研究就結束了，這將在 2025 年發生，這將關注 eGFR。此次中期分析的正面頂線結果表明，與安慰劑相比，在減少蛋白尿方面具有優越性，而這是在優化支持性治療的基礎上實現的。這個結果具有臨床意義，具有高度的統計意義。我認為對我們所看到的結果非常非常滿意。

Safety profile was consistent with what we've previously shown, and again, as you know, in oral medicine. So we're in discussions with FDA now to submit the medicine for accelerated approval. The study continues to a blind ed to assess superiority in eGFR slope.

安全性與我們之前所展示的一致，正如您所知，在口腔醫學領域也是如此。因此，我們現在正在與 FDA 討論提交該藥物以加速批准。研究繼續進行盲法評估 eGFR 斜率的優越性。

Next slide, please. Now turning to Lutathera. This was a positive surprise that we had in the quarter, which is the Phase III NETTER-2 results, which highlighted the potential for radioligand therapy in earlier disease settings. And this is consistent with what we've reviewed earlier with Pluvicto. It does appear as we move these radioligand therapies into earlier lines, we're seeing stronger results than we saw even in the later lines. We also saw strong results.

請下一張投影片。現在轉向盧塔瑟拉。這是我們在本季度獲得的一個積極的驚喜，即 III 期 NETTER-2 結果，它強調了放射配體治療在早期疾病環境中的潛力。這與我們之前與 Pluvicto 的評論一致。當我們將這些放射性配體療法轉移到早期產品線時，我們確實看到了比後期產品線更強的結果。我們也看到了強勁的成果。

In this study, we demonstrated a clinically meaningful significant benefit. We met the primary endpoint for PFS, the secondary endpoints for overall response rate. The safety was consistent. This study randomized 2:1 Lutathera over octreotide LAR versus high-dose octreotide LAR. And we followed up every 6 months for 3 years. So what this allows us to do, and important to note that Lutathera technically already has this indication within its U.S. label, but without data to support its widespread use.

在這項研究中，我們證明了具有臨床意義的顯著益處。我們達到了 PFS 的主要終點和整體緩解率的次要終點。安全性是一致的。本研究以 2:1 的比例將 Lutathera 與奧曲肽 LAR 和高劑量奧曲肽 LAR 進行隨機化。我們每 6 個月進行一次隨訪，持續了 3 年。那麼這讓我們能夠做什麼，重要的是要注意，從技術上來說，Lutathera 已經在其美國標籤中包含了這種適應症，但沒有數據可以支持其廣泛使用。

This data would allow us to move Lutathera from the second, third line, which covers about 30% to 45% of patients into the frontline setting where over 50% of patients with GEP-NET are treated currently with various SSAs. This would allow us then to add Lutathera on top and really, I think, benefit these patients in a really meaningful way. So we plan to present this data in the first part of next year. And in the case of the U.S., we wouldn't need further label expansion and we plan to really move forward and educating the community on the importance of this data to move Lutathera into the frontline setting and in other jurisdictions around the world will now evaluate how to further expand the label from a regulatory standpoint.

這些數據將使我們能夠將 Lutathera 從覆蓋約 30% 至 45% 患者的二線、三線轉移到一線環境，其中超過 50% 的 GEP-NET 患者目前正在接受各種 SSA 治療。這將使我們能夠在上面添加 Lutathera，我認為，這確實會以一種非常有意義的方式使這些患者受益。因此，我們計劃在明年上半年提供這些數據。就美國而言，我們不需要進一步擴展標籤，我們計劃真正向前推進，教育社區了解這些數據的重要性，以將 Lutathera 推向一線環境，而世界其他司法管轄區現在將評估如何從監管角度進一步擴大標籤範圍。

So moving to the next slide. With that, I'll hand it over to Harry.

現在轉到下一張投影片。這樣，我就把它交給哈利了。

Yes. Thank you very much, Vas. Good morning, good afternoon, everybody. I'm now going to walk you through some of the financials for the third quarter and the first 9 months. As always, my comments refer to growth rates in constant currencies, unless otherwise noted. Also, throughout the presentation, I'm only going to talk about continuing operations. Just as a reminder, that continuing operations include the retained business activities of Novartis comprising of the Innovative Medicines Division and the continuing corporate activities, which is, of course, the majority of them.

是的。非常感謝你，瓦斯。大家早安，下午好。現在我將向您介紹第三季和前 9 個月的一些財務數據。像往常一樣，除非另有說明，我的評論指的是按固定貨幣計算的增長率。此外，在整個演示過程中，我只會談論持續營運。需要提醒的是，持續經營業務包括諾華保留的業務活動（包括創新藥物部門）和持續的企業活動，當然，這是其中的大部分。

Discontinued operations include Sandoz and selected smaller parts of corporate activities attributable to the Sandoz business, as well as certain expenses related to the spin-off.

終止的業務包括山德士和山德士業務中選定的較小部分的企業活動，以及與分拆相關的某些費用。

Let's go to the next slide, please. Before I go into the details of our robust performance in quarter 3 and year-to-date, I wanted to show you this slide with restated numbers post the Sandoz spin so that you can have a like-for-like comparison. We published these restated numbers also a couple of weeks ago on our website in order to help you with your modeling. In due course, we will also provide continued operations numbers for years before '22.

請轉到下一張投影片。在詳細介紹我們在第三季和今年迄今的強勁業績之前，我想向您展示這張投影片，其中包含山德士重組後重述的數字，以便您可以進行同類比較。幾週前，我們也在我們的網站上發布了這些重述的數字，以幫助您進行建模。在適當的時候，我們還將提供 22 年之前的持續營運數據。

On this slide, we want to illustrate a strong continuing operations performance throughout 2023. And for the net sales and core operating income, as you can see, we had strong consistent growth, we have also tried of course, our margin improvement. And in addition to the sales growth, the cost savings related to our ongoing productivity programs that we started last year also contributed to our significant core margin expansion.

在這張投影片上，我們希望展現整個2023 年強勁的持續營運績效。對於淨銷售額和核心營業收入，正如您所看到的，我們有強勁的持續成長，當然，我們也嘗試了利潤率的提高。除了銷售成長之外，我們去年啟動的持續生產力計畫帶來的成本節約也促進了我們核心利潤率的大幅成長。

Next slide, please. So Slide 24 details the robust double-digit top and bottom line performance during quarter 3 and for the first 9 months. The top line grew 12% in the quarter and 10% year-to-date, with broad-based performance across our core therapeutic areas and key geographies. Core operating income was up 21% in quarter 3 and 19% in the first 9 months, again, mainly driven by higher sales and savings from the ongoing productivity despite a bit of inflation, which is very much in line with what we outlooked earlier this year.

請下一張投影片。因此，投影片 24 詳細介紹了第三季和前 9 個月強勁的兩位數頂線和底線業績。本季營收成長 12%，年初至今成長 10%，在我們的核心治療領域和關鍵地區都有廣泛的業績。儘管存在一定的通貨膨脹，但第三季度的核心營業收入增長了21%，前9 個月的核心營業收入增長了19%，這主要是由於銷售額的增加和持續生產力帶來的節省，這與我們今年早些時候的預期非常一致年。

Core EPS grew 29% to $1.74 in the quarter and 28% to $4.95 in the first 9 months. Core EPS grew, as you can see, a bit faster than core operating income, helped by our ongoing share buyback program.

本季核心每股收益成長 29%，至 1.74 美元，前 9 個月成長 28%，至 4.95 美元。正如您所看到的，核心每股盈餘的成長速度比核心營業收入的成長速度要快一些，這得益於我們正在進行的股票回購計畫。

We also delivered very healthy free cash flow with $5 billion in the quarter, which, as we look back, is the highest quarter in over 5 years for us, and $11 billion in the first 9 months. To note, quarter 3 net sales growth of 12% benefited from about 2 points from one-off items that are unlikely to recur in the future, including Kesimpta revenue reduction adjustment in Europe, which Vas mentioned when he reviewed the Kesimpta slide. As well as in there, we have in our net sales now that Sandoz is a third-party, separate company. We have also our contract manufacturing to Sandoz in our contract manufacturing sales line, you see that actually also in our interim financial report as a separate line.

我們也提供了非常健康的自由現金流，本季為 50 億美元，回顧過去，這是我們 5 年來最高的季度，前 9 個月為 110 億美元。需要注意的是，第三季淨銷售額成長12%，得益於未來不太可能重複出現的一次性項目約2 個百分點，其中包括Vas 在審查Kesimpta 幻燈片時提到的歐洲Kesimpta 收入削減調整。此外，由於山德士是第三方獨立公司，我們的淨銷售額也有所增加。我們的合約製造銷售線中還有山德士的合約製造，您實際上也在我們的中期財務報告中看到了這一點，作為一個單獨的線。

And in the quarter, we had around $100 million, $150 million higher sales to Sandoz as some inventory buildup as part of the spinoff happened, right? Sure, we can talk about it later. But operationally, the underlying growth was more in line with 10% in the quarter versus the reported of 12%.

在本季度，我們對 Sandoz 的銷售額增加了約 1 億美元，比分拆過程中庫存增加了 1.5 億美元，對嗎？當然，我們可以稍後再討論。但從營運角度來看，本季的基本成長更接近 10%，而不是報告的 12%。

But still, in summary, a very strong first 9 months of the year as our efforts to focus and streamline the business continue to pay off.

但總而言之，今年前 9 個月的表現仍然非常強勁，因為我們專注於和簡化業務的努力繼續得到回報。

On the next slide, Page 25. Yes, this chart becomes -- gets less and less rows. Those of you who are with us a long time, right, we started with 6 or 7 rows now we basically have 1 left. And of course, we do show the first 9 months of discontinued operation. But the full focus is on our new shape as a focused innovative medicines company, sort of continuing operations. So again, you see the net sales growth and all of that, which I explained beforehand, and Vas, but certainly, Kesimpta, Entresto, Kisqali and Pluvicto once again stood out as growth contributed in the quarter.

在下一張投影片上，第 25 頁。是的，該圖表變得——行數越來越少。跟我們在一起很久的人對吧，我們一開始有6、7排，現在基本上只剩下1排了。當然，我們確實顯示了停止營運的前 9 個月。但重點是我們作為一家專注於創新的藥品公司的新形態，即持續經營。所以，你再次看到淨銷售額的成長和所有這些，我之前解釋過，還有 Vas，但當然，Kesimpta、Entresto、Kisqali 和 Pluvicto 再次脫穎而出，為本季的成長做出了貢獻。

And with that, of course, our increase in core operating income and margin to 37.4% in the quarter, which is quite similar to our year-to-date 36.9% core margin. And more importantly, even as we are tracking very well to reach our 40% target for margins in the midterm. And to note, our margin is now calculated on net sales, which includes sales to discontinued operations and future Sandoz contract manufacturing.

當然，我們本季的核心營業收入和利潤率也隨之增加至 37.4%，這與我們年初至今 36.9% 的核心利潤率非常相似。更重要的是，儘管我們正在順利實現中期 40% 的利潤率目標。值得注意的是，我們的利潤率現在是根據淨銷售額計算的，其中包括對已終止經營業務和未來山德士合約製造的銷售額。

Slide 26, please. Yes. Guidance also becomes a bit simpler, right? So here is our guidance. We continue to expect sales to grow high single digit. However, we raised the guidance for core operating income by 2 notches to grow mid- to high teens, up from the low double digit to mid-teens. We do expect to see continuing strong sales growth in quarter 4 and likely expect to be at the high end of the sales range guidance. It's even possible we might just hit the 10% growth on revenue for the full year given we have delivered 10% in the first 9 months.

請投影片 26。是的。指導也變得簡單了一些吧？這是我們的指導。我們繼續預期銷售額將成長高個位數。然而，我們將核心營業收入指引提高了兩個檔次，從低兩位數上升到中雙位數。我們確實預計第四季度的銷售將持續強勁成長，並可能達到銷售指引範圍的高端。鑑於我們在前 9 個月實現了 10% 的成長，我們甚至有可能實現全年營收成長 10%。

Our key assumption continues to be that there are no Entresto generics, nor Sandostatin LAR generics entering in the U.S. in 2023.

我們的主要假設仍然是，2023 年不會有 Entresto 仿製藥或 Sandostatin LAR 仿製藥進入美國。

Next slide, please. So we are committed, of course, to create value for our shareholders. I've tried to summarize this here on 1 page, some of the corporate actions we have taken over the years, if you will. And that, of course, is there to bolster our future growth as well in our replacement power. And we have, as you know, a substantial cash generation from our operations, which allows us to do both, invest optimally in our organic business and bolt-on M&A and BD&L deals, as well as returning capital back to our shareholders.

請下一張投影片。因此，我們當然致力於為股東創造價值。如果你願意的話，我試著在一頁上總結我們多年來採取的一些企業行動。當然，這也是為了支持我們未來的成長以及我們的替代能力。如您所知，我們的營運產生了大量現金，這使我們能夠兩件事都做到：對我們的有機業務以及補充併購和 BD&L 交易進行最佳投資，並將資本返還給我們的股東。

The majority of the reinvested capital funds R&D, and we have spent over $45 billion in the past 5 years in R&D. Of course, we supplement this with business development in the form of bolt-on acquisitions in our core therapeutic areas. The other side of the equation is what we return to our shareholders with a strong and growing dividend in Swiss franc over many years since the company creation and that will be continuing so in the future, including through the spin-offs of Alcon and Sandoz, for which we never have and will rebase.

大部分再投資資本用於研發，過去 5 年我們在研發上的支出超過 450 億美元。當然，我們透過在核心治療領域進行補強收購的形式進行業務發展來補充這一點。等式的另一邊是，自公司創建以來的許多年裡，我們以強勁且不斷增長的瑞士法郎股息回報股東，並且在未來將繼續如此，包括通過分拆愛爾康和山德士，我們從來沒有也將為此重新設定基礎。

In addition, we have also completed over $30 billion of share buybacks during the past 5 years, and we just initiated, as you know, a new share buyback of up to $15 billion in July this year. Not to be forgotten is that we have also created value via major strategic actions, which you see here at the bottom. As Vas mentioned, we have created new businesses, in a tax-efficient way with Alcon and most recent Sandoz spin-offs to become the global leader in eye care and generic sector. Alongside this, we have exited the Roche stake at an attractive valuation. And of course, we divested the Consumer joint venture stake in 2018. With that, I'll hand it back to Vas.

此外，過去5年我們也完成了超過300億美元的股票回購，如你所知，我們今年7月剛啟動了高達150億美元的新股票回購。不要忘記，我們也透過重大策略行動創造了價值，您可以在底部看到這一點。正如 Vas 所提到的，我們以節稅的方式與愛爾康和最近的山德士分拆公司一起創建了新業務，成為眼保健和仿製藥領域的全球領導者。除此之外，我們還以有吸引力的估值退出了羅氏股份。當然，我們在 2018 年剝離了消費者合資企業的股份。這樣，我會將其交還給 Vas。

Great. Thanks, Harry. Thanks, Harry. In summary, if we go over to Slide 29, we had a very strong quarter 3 as you saw a 12% growth, 21% core operating income growth, which really demonstrates that the transformed Novartis with our focused strategy is delivering growth drivers are continuing to perform well, and we'll continue to work hard to accelerate them further. A lot of pipeline milestones, and we look forward to additional data that will be generated over the coming quarters and years.

偉大的。謝謝，哈利。謝謝，哈利。總而言之，如果我們看投影片 29，我們的第三季表現非常強勁，成長了 12%，核心營業收入成長了 21%，這真正表明轉型後的諾華和我們的重點策略正在持續提供成長動力表現良好，我們將繼續努力進一步加速它們。許多管道里程碑，我們期待在未來幾季和幾年內產生更多數據。

As Harry highlighted, the completion -- completed the spin of Sandoz, and now we've raised our 2023 guidance. And with that, I want to hand it to Samir to highlight our Capital Markets day...

正如 Harry 所強調的那樣，山德士的轉型已經完成，現在我們提高了 2023 年的指導。說到這裡，我想把它交給薩米爾來強調我們的資本市場日...

Yes. Just a quick plug for our Capital Markets Day, which will be in person as well as webcast at the end of November from London. Obviously, we're going to focus on our key R&D assets, which would include Kisqali, Pluvicto, Scemblix, iptacopan and remibrutinib. In addition, there will be a short update on strategy from Vas.

是的。簡單介紹一下我們的資本市場日，將於 11 月底在倫敦舉行現場直播和網路直播。顯然，我們將專注於我們的關鍵研發資產，其中包括 Kisqali、Pluvicto、Scemblix、iptacopan 和 remibrutinib。此外，Vas 也將發布簡短的策略更新。

And with that, we'll hand the course for the Q&A.

至此，我們將提交問答課程。

Yes. (Operator Instructions) Operator?

是的。 （操作員指示）操作員？

(Operator Instructions) And the first question comes from the line of Andrew Baum from Citi.

（操作員說明） 第一個問題來自花旗銀行的 Andrew Baum。

Has the probability that you unblind ORION-4, your cardiovascular outcome trial at an interim next year materially increased. The reason for the question is the IRA has obviously increased the urgency to accelerate Leqvio in the U.S. ORION-4 is a very well-powered trial. If you unblind next year, you know you're going to get significance with the magnitude of MACE way higher than the 15% of the monoclonals, though perhaps less than 30% if you waited until 2026.

如果您解除了 ORION-4 的盲法，明年中期的心血管結果試驗將大幅增加。提出這個問題的原因是，IRA 顯然增加了在美國加速 Leqvio 的緊迫性。ORION-4 是一項非常強大的試驗。如果明年揭盲，您就會知道 MACE 的嚴重程度將遠高於單株抗體的 15%，但如果等到 2026 年，這一數字可能還不到 30%。

You've got your Victorian-2P second outcome trial to show a significant reduction in MACE and likely CV death in '27. So it would seem to me that this is a very viable opportunity. Alternatively, do you think you need to have a 30% MACE reduction because of the competition from -- in the near term Amsterdam and then Merck with their [role] at the end of the decade?

您的 Victorian-2P 第二結果試驗顯示，27 年 MACE 和可能的 CV 死亡顯著減少。所以在我看來，這是一個非常可行的機會。或者，您是否認為您需要將 MACE 減少 30%，因為短期內有來自阿姆斯特丹的競爭，然後是本世紀末默克的[角色]？

Thanks, Andrew. Great question. So first on ORION-4, the study is fully enrolled. And I think we've been able to manage the study well with the NHS and the U.K. teams that we're working with. And so the study is very much on track.

謝謝，安德魯。很好的問題。因此，首先在 ORION-4 上，該研究已全部入組。我認為我們已經能夠與 NHS 和我們合作的英國團隊很好地管理這項研究。所以這項研究已經步入正軌。

We currently continue to plan to follow these patients out for the -- this was -- rather than doing an event-based study, we're doing a time-based study because of the data sets that you obviously know well that indicated that with further follow-up in these studies, you can get on the order of 30% CVRR. And that continues to be our strategy, of course, with Victorian-2 Prevent and in Victoria-1 Prevent also now running as well. Of course, we'll continue to assess as we move forward. We don't have any plants on unblind.

我們目前繼續計劃追蹤這些患者，而不是進行基於事件的研究，而是進行基於時間的研究，因為您顯然很了解的數據集表明，在這些研究的進一步跟進中，可以獲得30% CVRR 的量級。當然，這仍然是我們的策略，維多利亞-2 Prevent 和 Victoria-1 Prevent 也正在運作。當然，我們將在前進的過程中繼續評估。我們沒有任何植物處於開啟狀態。

Now with -- and the reason for that is we believe that having a very compelling data set on the order of significant -- with that sort of significant CVRR will set us up well, not only for Leqvio, but our subsequent portfolio of SiRNAs, which we continue to advance, including, of course, longer-acting SiRNAs that hopefully can be administered once a year, combination SiRNAs, that are all currently being worked on within our research labs.

現在——原因是我們相信，擁有一個非常引人注目的、具有顯著 CVRR 的數據集，將為我們做好準備，不僅對 Leqvio，而且對我們後續的 SiRNA 產品組合，我們將繼續推進這些技術，當然包括有望每年施用一次的長效SiRNA、組合SiRNA，這些目前都在我們的研究實驗室中進行研究。

I would also say we're very focused and determined on trying to address the IRA in total to get to 9 to 13 for the all small molecule and NDA drugs, but also specifically to address the issue of genetically targeted drugs, siRNAs and ASOs, where there has been bipartisan legislation tables and we're hoping (technical difficulty).

我還想說，我們非常專注並決心努力解決 IRA 問題，使所有小分子和 NDA 藥物的 IRA 總數達到 9 到 13，而且還專門解決基因靶向藥物、siRNA 和 ASO 的問題，我們希望有兩黨立法表（技術難度）。

And 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。

A question on Pluvicto, please. So from the slides that we see, your peak sales target remains unchanged over USD 2 billion. And I recall previously, you noted success in the first-line setting to significantly expand the target patient population. So I wonder if you could just walk us through your -- what your peak sales guidance assumes with regard to indications approved? And whether there's a specific reason why you've not raised that target post PSMAfore readout?

請教一個關於 Pluvicto 的問題。因此，從我們看到的幻燈片來看，你們的高峰銷售目標保持在 20 億美元以上不變。我記得之前，您注意到在一線環境中取得了成功，顯著擴大了目標患者群體。所以我想知道您是否可以向我們介紹一下您的峰值銷售指導對已批准的適應症的假設？ PSMAfore 公佈後您沒有提高該目標是否有具體原因？

Yes. Thanks, Kerry. So we continue to believe Pluvicto is going to be a multibillion-dollar medicine. We're guiding to the rounded $1 billion on VISION in its first full year of launch, and we continue to see runway in the VISION population on its own to continue to grow at a healthy clip into next year. PSMAfore will obviously significantly expand depending on the final population 2 to 3x from where we are today with VISION. And it's important to know, we still haven't really launched Pluvicto outside of the United States in a really meaningful way. So there's opportunity for global expansion as well.

是的。謝謝，凱瑞。因此，我們仍然相信 Pluvicto 將成為一種價值數十億美元的藥物。我們預計 VISION 在推出的第一年全年將達到 10 億美元，我們繼續看到 VISION 群體在明年繼續健康成長。 PSMAfore 顯然將顯著擴大，具體取決於最終人口數量，是我們今天 VISION 的 2 到 3 倍。重要的是要知道，我們還沒有真正以真正有意義的方式在美國境外推出 Pluvicto。因此，也存在全球擴張的機會。

Then stepwise from there, the PSMA EDITION study, which moves us into the hormone-sensitive setting with a readout in 2024, also has the potential of a further expansion on the level of what we would get from PSMAfore, so a similar expansion in patient population that's addressable. We've also launched additional studies in biochemical recurrence in oligometastatic prostate cancer moving into even earlier lines. Certainly, the potential is here for the medicine to be a very significant medicine. And so that will, of course, depend on the data sets and the timings of approval.

然後從那裡逐步開始，PSMA EDITION 研究將我們帶入激素敏感環境，並在 2024 年公佈結果，也有可能進一步擴大我們從 PSMAfore 獲得的水平，因此患者的類似擴展可尋址的人口。我們也針對寡轉移性攝護腺癌的生化復發進行了更多研究，進入更早的階段。當然，這種藥物有可能成為一種非常重要的藥物。當然，這將取決於資料集和批准的時間。

We don't plan to provide any sort of peak sales guidance at the moment beyond what we've already provided on Cosentyx and Entresto. We will do that as the product gets more mature, additional data sets come out, and we'll be in a better position to guide you as to how large the medicine could be.

除了我們已經對 Cosentyx 和 Entresto 提供的指導外，我們目前不打算提供任何形式的高峰銷售指導。隨著產品變得更加成熟，更多資料集出現，我們將這樣做，我們將能夠更好地指導您了解藥物的大小。

Your next question comes from the line of Emmanuel Papadakis from DB.

您的下一個問題來自 DB 的 Emmanuel Papadakis。

Perhaps I can start with Pluvicto and 'try and squeeze in a question I didn't get the chance to ask on the call beforehand. The question is really just relating to the trial design. In your estimation, what percent of patients are typically eligible for a switch of ARPI rather than being moved to chemotherapy?

也許我可以從 Pluvicto 開始，「試著擠進一個我事先沒有機會在電話中問的問題」。問題其實只是與試驗設計有關。根據您的估計，有多少百分比的患者通常適合更換 ARPI 而不是轉為化療？

And do you think adoption will be restricted to that switch subgroup based on the data? I'm asking because you've emphasized it will triple the eligible patient population with PSMAfore result. But obviously, you do not have any head-to-head chemotherapy data. So do you think physicians are going to extrapolate this beyond just confidence in use in that ARPI switch up group? Or is it really going to be restricted to that subgroup in its own or anyway...

您認為根據數據，採用將僅限於該交換器子組嗎？我問這個問題是因為您強調過，這將使符合 PSMAfore 結果的合格患者人數增加兩倍。但顯然，您沒有任何頭對頭化療數據。那麼，您認為醫生是否會在 ARPI 切換組的使用信心之外推斷出這一點？或者它真的會被限制在該子組中嗎？

Yes. Thanks, Emmanuel. So I think one of the things to note is it's much more -- we like to think of these things as linear, but it's much more fluid and very dependent on how you assess patients. I think there's going to be a few dynamics that will determine when Pluvicto is approved in the PSMAfore population, how it will be utilized. One, we know there's a large number of patients who, in the end -- a large proportion of patients who are chemo ineligible for a variety of reasons. And those patients, of course, would be patients you would want to use an alternative therapy like Pluvicto in.

是的。謝謝，伊曼紐。因此，我認為需要注意的一件事是，我們喜歡將這些事情視為線性的，但它更加流動，並且非常依賴您如何評估患者。我認為，將有一些動態因素決定 Pluvicto 何時在 PSMAfore 人群中獲得批准以及如何使用。第一，我們知道有大量患者最終——很大一部分患者由於各種原因不符合化療資格。當然，這些患者是您想要使用 Pluvicto 等替代療法的患者。

We also know that there is a rapid expansion of F-18 PET scans that are being used in the metastatic population. And if you have an F-18 PET that's positive for PSMA, you might opt to use Pluvicto because obviously, you can treat to the scan, and you might use that ahead or after ARPI depending on the clinician's decision.

我們也知道，F-18 PET 掃描在轉移人群中的應用正在迅速擴大。如果您的 F-18 PET 對 PSMA 呈陽性，您可能會選擇使用 Pluvicto，因為顯然，您可以對掃描進行治療，並且您可以在 ARPI 之前或之後使用，具體取決於臨床醫生的決定。

So I think there's going to be a very fluid nature in this pre-chemo setting where there's going to be ARPIs, there's going to be Pluvicto, maybe some physicians want to cycle ARPIs. But I think what we can say is that versus what we currently address in the VISION population, and we still have a significant opportunity just to expand within the VISION population. We would expect a significant increase with the move into that pre-taxane setting.

因此，我認為在化療前的環境中將會存在非常多變的性質，其中將會有 ARPI，將會有 Pluvicto，也許有些醫生想要循環 ARPI。但我認為我們可以說的是，與我們目前在 VISION 人群中解決的問題相比，我們仍然有很大的機會在 VISION 人群中進行擴展。我們預計，隨著進入紫杉烷前環境，該值將顯著增加。

As Jeff also highlighted, we do have Phase II data that was generated as well in a head-to-head versus chemos, of course, not fully powered, but I think it did also indicate that Pluvicto compares favorably to so-called therapy study favorably versus chemo as well.

正如 Jeff 也強調的那樣，我們確實有在頭對頭與化療對比中產生的 II 期數據，當然，這些數據並不完全有效，但我認為這也表明 Pluvicto 與所謂的治療研究相比具有優勢也優於化療。

So I think a lot of data there that physicians can utilize. And speaking to at least my own conversations, I'm sure all of you will have your own interviews with them at ESMO, I think there's a lot of excitement. And I think the excitement is driven both by the efficacy of Pluvicto, but as important is the safety. And I think one of the things that's a shift in cancer care right now is that patients are demanding therapies that maintain or at least enable them to have a reasonable quality of life.

所以我認為醫生可以利用很多數據。至少就我自己的對話而言，我相信你們所有人都會在 ESMO 接受他們自己的採訪，我認為這很令人興奮。我認為這種興奮既是由 Pluvicto 的功效驅動的，但同樣重要的是安全性。我認為目前癌症護理的轉變之一是患者需要維持或至少使他們能夠擁有合理生活品質的治療。

And one of the reasons we see -- we believe we see some strong uptake of Pluvicto in the VISION population is Pluvicto is very well tolerated. We certainly have some issues with the xerostomia and some mild issues as well with bone marrow, but overall, well managed and much better tolerated than some of the alternative therapies.

我們認為，我們看到 VISION 族群對 Pluvicto 的強烈吸收的原因之一是 Pluvicto 的耐受性非常好。我們當然存在一些口乾症問題和一些輕微的骨髓問題，但總體而言，與某些替代療法相比，管理良好且耐受性更好。

If you looked at the data that Jeff presented, even versus a switch ARPI, you saw lower rates of severe adverse events as well as Grade 3/4 adverse events, which again indicates that this is end of quality of life indicators. This is a well-tolerated therapy for patients. And I think there will be patient demand to avoid having to be on heavier loads of either ARPI or chemo if they can have a safe, highly-effective therapy. So I think all of those are favorable. But of course, there will be patients who physicians choose to cycle through ARPI as well.

如果您查看 Jeff 提供的數據，即使與轉換 ARPI 相比，您也會發現嚴重不良事件以及 3/4 級不良事件的發生率較低，這再次表明這是生活品質指標的終結。這是一種患者耐受性良好的療法。我認為，如果患者能夠獲得安全、高效的治療，他們就會要求避免承受更大的 ARPI 或化療負荷。所以我認為所有這些都是有利的。當然，醫生也會選擇對某些患者進行 ARPI 循環。

So not a direct answer, but I hope that gives you some of the dynamics that we'll certainly be working on over the coming years.

所以這不是一個直接的答案，但我希望這能給你一些我們在未來幾年肯定會努力的動力。

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。

On emerging markets, you delivered pretty consistent growth quarter-over-quarter. I was just wondering how confident are you to continue to deliver such growth? Or is there any loss of exclusivity to come in certain countries, notably in China that could impact this trajectory?

在新興市場，您實現了季度環比相當穩定的成長。我只是想知道您對繼續實現這樣的成長有多大信心？或者某些國家（尤其是中國）的獨家經營權是否會喪失，進而影響這一發展軌跡？

Yes. Thanks, Florent. I mean so we have, I think, very good growth in our international markets. In Europe, of course, we're currently working on overcoming a number of expiries that we have. You have -- certainly Lucentis has recently gone off. You have other medicines that have recently gone off as well. And so the European growth has moderated and then we expect Europe to come back now over the coming years as new medicines launch to replace those expiring therapies.

是的。謝謝，弗洛倫特。我的意思是，我認為我們在國際市場上有非常好的成長。當然，在歐洲，我們目前正在努力克服一些到期問題。當然，Lucentis 最近已經離開了。您還有其他藥物最近也失效了。因此，歐洲的成長已經放緩，然後我們預計歐洲將在未來幾年內捲土重來，因為新藥的推出將取代那些即將到期的療法。

China is seeing very robust growth, double-digit growth, which we continue to see in that market. We will, of course, come up against Entresto inclusion in the BBP framework, but we expect we'll be able to manage that. And then with the launches of other medicines, including Cosentyx, Leqvio, to continue the strong growth in China. Japan is growing double-digit at the moment on the back of the Entresto launch, and we'll soon be launching Leqvio as well in Japan. So very dynamic performance in the Japanese market.

中國正在經歷非常強勁的成長，兩位數的成長，我們在該市場上繼續看到這種成長。當然，我們會反對將 Entresto 納入 BBP 框架，但我們希望我們能夠解決這個問題。然後隨著包括 Cosentyx、Leqvio 在內的其他藥物的上市，繼續在中國的強勁成長。在 Entresto 推出後，日本目前正在實現兩位數的成長，我們很快也將在日本推出 Leqvio。日本市場的表現非常活躍。

So with all of those dynamics, we expect the international markets to continue to have very solid growth over the coming years. And that's driven primarily by the new launches.

因此，鑑於所有這些動態，我們預計國際市場在未來幾年將繼續保持非常穩健的成長。這主要是由新產品的推出所推動的。

We will now take the next question and the question comes from the line of Seamus Fernandez from Guggenheim Securities.

我們現在將提出下一個問題，該問題來自古根漢證券公司的 Seamus Fernandez。

So just to -- can you quantify the magnitude of contribution from Kesimpta in the quarter? And also just give us a sense of the directional trajectory? And then just a second question we've been getting from investors repeatedly on PSMAfore relative to the FDA, just wondering, relative to the Lumakras questions that were raised around that study and trial design, how confident are you that PSMAfore is on track for approval? And can you just update us on the timing of the filing?

那麼，您能否量化 Kesimpta 在本季的貢獻程度？並且也只是讓我們了解方向軌跡？然後，我們反覆從投資者那裡收到關於 PSMAfore 相對於 FDA 的第二個問題，只是想知道，相對於圍繞該研究和試驗設計提出的 Lumakras 問題，您對 PSMAfore 有望獲得批准有多大信心？您能否向我們介紹一下提交時間的最新情況？

Yes. Thanks, Seamus. So on Kesimpta, Harry?

是的。謝謝，西莫。那麼關於 Kesimpta 嗎，哈利？

As I assume the onetime contribution from the revenue deduction, right? So as you have seen, Kesimpta overall contributed $368 million as growth to the quarter, right, being now close to $660 million total sales. And of that, roughly $110 million is from this revenue deduction true-up. So if you take that out, still significant contribution of roughly $250 million, $260 million and also still a growth of 86%. Is that answering your question?

正如我假設的一次性貢獻來自收入扣除，對吧？正如您所看到的，Kesimpta 本季的成長總體貢獻了 3.68 億美元，目前總銷售額接近 6.6 億美元。其中，約 1.1 億美元來自此項收入扣除調整。因此，如果去掉這一點，仍然有大約 2.5 億美元、2.6 億美元的重大貢獻，而且仍然成長 86%。這是回答你的問題嗎？

Yes.

是的。

Yes. On -- I will allow the second question this time, Seamus. So on PSMAfore, so as I stated, our plan is to file with -- when we get to a 75% information fraction. And we do feel confident that given the overall data set that we have generated with respect to all of the data, you hopefully saw at ESMO and in the earlier presentation that we have a very compelling benefit/risk profile, and we'll have to then navigate that with the agency with respect to the adjusted OS and the unadjusted OS as well.

是的。關於——這次我允許提出第二個問題，Seamus。因此，在 PSMAfore 上，正如我所說，我們的計劃是，當我們達到 75% 的資訊比例時進行歸檔。我們確實有信心，考慮到我們生成的所有數據的總體數據集，您希望在 ESMO 和之前的演示中看到我們擁有非常引人注目的收益/風險概況，我們必須然後與該機構一起就調整後的作業系統和未調整的作業系統進行導航。

We're a little bit in new territory. And so far as the FDA, I think, has made a significant shift affecting all cancer drugs with respect to the expectations of OS at the filing with PFS. But I think this is a really unique situation from the other situations that you mentioned. One, this study was extremely well designed and well conducted.

我們有點進入新領域了。我認為，到目前為止，FDA 在向 PFS 提交的 OS 預期方面已經做出了重大轉變，影響所有癌症藥物。但我認為與你提到的其他情況相比，這是一個非常獨特的情況。第一，這項研究設計得非常好並且進行得很好。

And you look at the dropout rates, which were very low because we allow crossover. You look at the time frame with which we're collecting the data. If you look at the rigor with which we collected the data, and you look at the size of the PFS benefit, where you have a doubling of the PFS benefit, significant gains in ORR, significant gains in patient-reported outcomes, a very clear safe, clean safety profile. I think taken together, that is a very different profile than maybe what you were referring to.

你看看輟學率，因為我們允許交叉，所以輟學率非常低。您可以查看我們收集資料的時間範圍。如果你看看我們收集資料的嚴格程度，再看看 PFS 獲益的大小，你會發現 PFS 獲益翻倍，ORR 顯著提高，病人報告的結果顯著提高，這是一個非常明確的結果。安全、乾淨的安全設定檔。我認為綜合起來，這與您所指的可能非常不同。

In addition, we have demonstrated OS in another study as well, which I think is an important factor as well when you think about this. Our belief is that with a 75% information fraction, we'll have collected adequate data to demonstrate the overall profile of the medicine. We'll, of course, file it. We'll deal with the review questions and then manage it from there. But I think based on all of the feedback we've heard from physicians and experts very clear that this is an important medicine that needs to eventually get approved and get out to patients.

此外，我們還在另一項研究中展示了作業系統，我認為當你考慮這一點時，這也是一個重要因素。我們相信，憑藉 75% 的資訊分數，我們將收集足夠的數據來展示該藥物的整體概況。當然，我們會將其歸檔。我們將處理審核問題，然後從那裡進行管理。但我認為，根據我們從醫生和專家那裡聽到的所有回饋，非常清楚這是一種重要的藥物，需要最終獲得批准並提供給患者。

(Operator Instructions) The next question comes from the line of Simon Baker from Redburn.

（操作員說明）下一個問題來自 Redburn 的 Simon Baker。

A slightly bigger picture question. Back in early September, you announced that NIBR was changing its name. I wonder if you could update us on what else is changing beyond the name at NIBR?

一個稍微大一點的問題。早在九月初，你們就宣布 NIBR 將更名。我想知道您能否向我們介紹一下除了 NIBR 名稱之外還有哪些變化？

Yes. Thanks, Simon. We're excited about the outlook now for what we call now biomedical research within the company. We've made a number of changes in our overall R&D strategy. One, we're focusing very clearly now on 4 TAs, cardiorenal, neuroscience, oncology and immunology. And you've seen also, I hope, in our filings that we've had a significant pruning of the portfolio down to what we believe is now approaching peer median in terms of the size of the portfolio, but that allows us to increase the number of scientists that we have on each one of our projects, which we hope will accelerate the prosecution of those projects, get us to data and readouts quicker, and hopefully get us to more and higher-value medicines overall.

是的。謝謝，西蒙。我們對公司內部現在所謂的生物醫學研究的前景感到興奮。我們對整體研發策略做出了一些改變。第一，我們現在非常明確地關注 4 個 TA：心臟腎臟、神經科學、腫瘤學和免疫學。我希望您在我們的文件中也看到，我們對投資組合進行了大幅削減，我們認為就投資組合規模而言，目前已接近同行中位數，但這使我們能夠增加我們每個項目都有大量的科學家，我們希望這將加速這些計畫的實施，讓我們更快地獲得數據和讀數，並希望讓我們整體上獲得更多、更高價值的藥物。

So we've focused the portfolio and focused our R&D operations. Second, we've really created a system now where there's early commercial input even into research, something that Novartis had not really had between 2002 and last year. So now we have an integrated approach. We call it the RDC continuum, research, development and commercialization.

因此，我們專注於產品組合併專注於我們的研發業務。其次，我們現在確實創建了一個系統，其中甚至有早期的商業投入甚至研究，這是諾華在 2002 年到去年之間真正沒有的。所以現在我們有了一個綜合的方法。我們稱之為 RDC 連續體，即研究、開發和商業化。

When we enter -- when we have a new project that's going to enter into the portfolio of research, that is reviewed by our executive leadership team to make sure we're all aligned that this is a medicine we want to pursue, it has significant potential, we do allow, of course, the appropriate amount of experimentation within biomedical research, but we want that early commercial input to ensure we're developing medicines that will matter for the world and matter for Novartis.

當我們進入——當我們有一個新項目將進入研究組合時，我們的執行領導團隊會對其進行審查，以確保我們都一致認為這是我們想要追求的藥物，它具有重大意義當然，我們確實允許在生物醫學研究中進行適當數量的實驗，但我們希望儘早進行商業投入，以確保我們正在開發對世界和諾華都重要的藥物。

So there is also improved integration between research, development and commercial. And then, in addition, we're trying to make research and development as seamless as possible. So now we are increasingly having integrated teams. So if you CART and immunology, if you look at radioligand therapies, and some of our key areas, we're having integrated research and development teams to ensure that projects move seamlessly Phase I, Phase II, no big handoffs, which I think will also enable us to move much faster.

因此，研究、開發和商業之間的整合也得到了改善。此外，我們也努力使研發盡可能無縫。所以現在我們越來越多擁有一體化的團隊。因此，如果你研究CART 和免疫學，如果你研究放射性配體療法，以及我們的一些關鍵領域，我們擁有整合的研發團隊，以確保計畫無縫地進行第一階段、第二階段，沒有大的交接，我認為這將也使我們能夠更快地採取行動。

And lastly, we're changing how we measure ourselves. We're measuring ourselves solely on do we generate medicines in research that advance into late-stage development. If we generate data that's interesting, but not advancing, if we generate data that's ultimately leading to out-licensed drugs, that's not the goal of our company. Our company has to be to use our research dollars to develop medicines and ultimately get to market, and that's what we're very much focused on as well.

最後，我們正在改變衡量自己的方式。我們衡量自己的唯一標準是我們是否能在研究中生產出可進入後期開發的藥物。如果我們產生的數據很有趣，但沒有進步，如果我們產生的數據最終導致藥物被超越許可，那麼這不是我們公司的目標。我們公司必須利用我們的研究資金來開發藥物並最終進入市場，這也是我們非常關注的。

So I'm very grateful for the NIBR team, or the research, I should say, biomedical research team doing a really good job with this new strategy and look forward to higher productivity from research in the years to come.

因此，我非常感謝 NIBR 團隊，或生物醫學研究團隊，他們在這項新策略方面做得非常出色，並期待在未來幾年的研究中取得更高的生產力。

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

您的下一個問題來自摩根大通的理查德·沃瑟（Richard Vosser）。

One on Cosentyx, please. Could you talk about your submission on HS? There's some discussion around in the market around potential label changes with regard to suicidal ideation, and I think one of your competitors has had placed on their IL-17 AF label. So just your thoughts on the submission time line, how that's going for HS? And also your thoughts on the emerging competition given that differential or different label that they have in terms of the warning?

請服用一份 Cosentyx 藥物。您能談談您對 HS 的提交嗎？市場上有一些關於自殺意念的潛在標籤變化的討論，我認為你們的競爭對手之一已經貼上了他們的 IL-17 AF 標籤。那麼您對提交時間軸的看法是，HS 的進展如何？鑑於他們在警告方面所具有的差異或不同標籤，您對新興競爭有何看法？

Yes. Thanks, Richard. So for the recent approval of Cosentyx and IV as well as our ongoing assessments of Cosentyx HS, we've had no indications of any changes to our safety labeling from what has already been established based on the 10 years of experience we have with Cosentyx in the market. Many hundreds of thousands of patients treated, many millions of patients -- ultimate patient years that we have on the medicine. So we have no indication, and we're in advanced discussions as well on the HS label right now for any labeling shifts. And that's based on the data that we've consistently generated with respect to all safety signals and the clean profile that I think Cosentyx has demonstrated consistently over time.

是的。謝謝，理查。因此，對於最近 Cosentyx 和 IV 的批准以及我們對 Cosentyx HS 的持續評估，我們沒有任何跡象表明我們的安全標籤與基於我們 10 年 Cosentyx 經驗所建立的安全標籤有任何變化。市場。數十萬名患者得到了治療，數百萬患者得到了治療——我們在藥物方面的最終患者年數。因此，我們沒有任何跡象表明，我們目前也在就 HS 標籤進行深入討論，以了解任何標籤變化。這是基於我們一直生成的關於所有安全信號的數據以及我認為 Cosentyx 隨著時間的推移始終如一地表現出的清潔特徵。

Now with respect to the competitiveness, given that Cosentyx does not have suicidal ideation, the need for liver enzyme monitoring and very low rates of candidiasis, we believe that Cosentyx is positively differentiated versus the competitor product. Our strong reimbursement positions in the U.S. as well as outside the U.S. markets puts us in a very strong footing against any entrant, especially an entrant that has to overcome some safety liabilities. So I think we're very well positioned in that regard.

現在就競爭力而言，鑑於Cosentyx沒有自殺意念、不需要肝臟酵素監測以及極低的念珠菌病發生率，我們認為Cosentyx與競爭對手產品相比具有積極的差異化優勢。我們在美國以及美國以外市場的強大報銷地位使我們在對抗任何進入者時都具有非常強大的基礎，尤其是必須克服一些安全責任的進入者。所以我認為我們在這方面處於非常有利的位置。

I would close by saying it's important to note that IL-17A inhibitors are distinct from IL-17AF inhibitors. Previously, as you all well know, brodalumab in 20 -- I think it was 2016, already has demonstrated that with IL-17F inhibition, you can have some of these adverse consequences for that medicine.

最後我想說的是，值得注意的是 IL-17A 抑制劑與 IL-17AF 抑制劑不同。先前，眾所周知，brodalumab 在 20 年（我想是 2016 年）已經證明，透過 IL-17F 抑制，您可能會對該藥物產生一些不良後果。

So I think mechanistically, it's also important to treat these medicines fundamentally different, and that's certainly what our position is as well. So looking forward for Cosentyx. The focus is continuing to drive and get back to growth in the U.S. behind the IV launch, as well as the upcoming HS approval in Europe, maintained a strong position in PSA, AS and psoriasis, but then also now drive the HS approval and then continue to complete the additional indications that we have ongoing to eventually reach the $7 billion peak sales that we've guided to.

因此，我認為從機制上講，對這些藥物進行根本不同的治療也很重要，這當然也是我們的立場。所以很期待Cosentyx。重點是繼續推動並恢復 IV 上市背後的美國成長，以及即將在歐洲獲得 HS 批准，在 PSA、AS 和牛皮癬方面保持強勢地位，但現在也推動 HS 批准，然後繼續完成額外的跡象，表明我們最終將達到我們所指導的70 億美元的峰值銷售額。

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

您的下一個問題來自美國銀行的格雷厄姆·帕里（Graham Parry）。

This one for Harry. So 3 this year. You've had positive NATALEE data, PSMAfore, iptacopan for C3, IgAN I should say, since your last midterm guidance. So just wondering when is the right time to update that midterm guidance and how conservative that's looking now? And does the PSMAfore OS data still pending actually push out when you might provide the market with an update on midterm?

這是給哈利的。所以今年3個。自上次中期指導以來，您已經獲得了積極的 NATALEE 數據、PSMAfore、C3 的 iptacopan、IgAN。所以只是想知道什麼時候是更新中期指導的合適時間以及現在看起來有多保守？當您向市場提供中期更新時，仍在等待中的 PSMAfore OS 數據是否真的會推出？

And then actually, I'll just (inaudible) follow up on about the market comparison as well. I think one of the issues that's being raised in the market valves is the fact that there were some issues around the conduct of VISION and the early dropout that we saw in that study around the PFS analysis. So then you actually have that data on label. So if perhaps you can just compare and contrast the conduct of PSMAfore with VISION on the PFS endpoint? And any concerns the FDA might have there would be useful.

實際上，我也會（聽不清楚）跟進市場比較。我認為市場閥門中提出的問題之一是 VISION 的實施存在一些問題，以及我們在圍繞 PFS 分析的研究中看到的早期退出。那麼標籤上其實就有了這些數據。那麼，您是否可以在 PFS 端點上比較和對比 PSMAfore 與 VISION 的行為？ FDA 可能存在的任何擔憂都是有用的。

Thanks, Harry, on the guidance.

謝謝哈利的指導。

I think those were 4 questions.

我認為這是 4 個問題。

Graham has about the same...

葛拉漢也有同樣的...

Graham, thank you. So I think overall, you nicely mentioned that we have taken up 3x the guidance this year, absolutely on top line 2x, now bottom line twice. I think in the end, of course, I don't think I've done it in my 10 years before, and it's not on purpose ever, right? Each moment of time, of course, we try to give you a very balanced picture.

格雷厄姆，謝謝你。所以我認為總的來說，你很好地提到，我們今年已經採用了 3 倍的指導，絕對是頂線的 2 倍，現在是底線的兩倍。我想，當然，我認為我在過去的十年裡並沒有這樣做過，而且這也不是故意的，對吧？當然，我們每時每刻都盡力為您提供非常平衡的畫面。

You would say it's, of course, a little bit prudent, yes, but not to this extent. And I think we have seen, I think Vas mentioned from the beginning, we have been positively surprised how well the whole -- entire Novartis team, we are now 76,000 colleagues, right, after the Sandoz's spin, have responded to our transformation for growth program and the focus as a single innovative medicines company.

當然，你會說這有點謹慎，是的，但還沒到這種程度。我想我們已經看到，瓦斯從一開始就提到，整個諾華團隊，我們現在有76,000 名同事，在山德士轉型之後，我們對我們的成長轉型做出瞭如此好的反應，這讓我們感到非常驚訝計劃和作為單一創新藥品公司的重點。

Of course, including some harder action, which in some countries depending on unit work, and so that took a bit longer of uncertainty, unfortunately. But now that we are through that, the majority is still here or there, some things to implement, we have seen that this gives us more agility, faster decision-making and better impact in the market. That's one thing.

當然，包括一些更嚴厲的行動，這在某些國家取決於單位工作，因此不幸的是，這需要更長的不確定性。但現在我們已經完成了這個過程，大多數人仍然在這裡或那裡，有些事情需要實施，我們已經看到這給了我們更多的靈活性，更快的決策和更好的市場影響力。這是一回事。

And on the bottom line, we do execute slightly ahead of plan that helps, right? But of course, the most important in any pharma company is, the top line growth that has been done so well. There's a little bit of market expansion by probably 1 or 2 points. IQVIA global market has grown faster in the end versus initial estimates beginning of the year, but it doesn't explain 2x top line upgrade.

最重要的是，我們確實稍微提前了計劃執行，這會有所幫助，對嗎？但當然，對於任何製藥公司來說，最重要的是表現出色的營收成長。市場有一點點擴張，可能有 1 或 2 個百分點。與年初的初步估計相比，IQVIA 全球市場最終的成長速度更快，但這並不能解釋 2 倍的營收升級。

So it's really the vast majority of that I contribute to our new leaner way of operating in the company. So from that standpoint, very confident that we continue to drive good growth. There's, of course, we have the LOEs, smaller points, but attractive growth. And then Vas will give an outlook on the midterm growth potential of the company at the R&D Day.

因此，這實際上是我為公司新的更精簡的營運方式做出的貢獻。因此，從這個角度來看，我們非常有信心繼續推動良好的成長。當然，我們有 LOE，較小的點，但具有吸引力的成長。然後Vas會在研發日對公司的中期成長潛力進行展望。

Absolutely. So we continue to hold to the 4% and 40% margin, '22 to '27, and then we'll update further in the R&D day, Graham. Now with respect to the VISION versus PSMAfore, it's very different situations. The VISION study was partially inherited. There was no crossover allowed in the VISION study, so you had a high dropout rate, which was one of the things that we had to navigate with the FDA.

絕對地。因此，我們將繼續保持 4% 和 40% 的利潤率，從 22 年到 27 年，然後我們將在研發日進一步更新，Graham。現在就 VISION 與 PSMAfore 而言，情況非常不同。 VISION研究是部分遺傳的。 VISION 研究中不允許交叉，因此退出率很高，這是我們必須與 FDA 合作解決的問題之一。

But ultimately, the compelling data set, both for rPFS, which then was not included in the label because of the dropout issue, but OS, which was in the outstanding safety profile, we were able to bring the medicine to patients without going to an advisory committee.

但最終，令人信服的數據集，無論是 rPFS（由於退出問題而未包含在標籤中），還是 OS（具有出色的安全性），我們能夠將藥物帶給患者，而無需去醫院就診。諮詢委員會。

Contrast that to PSMAfore, where it was a very patient-friendly study, highly -- well-conducted, low dropout rate. I think when you look at the conduct of the study, very highly -- high integrity study that was conducted. And so really a very different situation and one where we really followed the guidance that FDA has given, which they encourage crossover for cancer studies because they want patients -- patient-friendly studies supported by the patient community so when a patient progresses, they should be able to cross over onto the experimental therapy to achieve the full benefit.

與 PSMAfore 形成鮮明對比的是，這是一項對患者非常友善的研究，實施良好，退出率低。我認為，當你觀察這項研究的進行時，你會發現這項研究的完整性非常高。因此，這確實是一種非常不同的情況，我們確實遵循了FDA 給出的指導，他們鼓勵癌症研究的交叉，因為他們想要患者——患者社區支持的患者友好型研究，因此當患者病情進展時，他們應該能夠跨入實驗療法以實現全部益處。

Now what we have to navigate is, on the one hand, FDA encouraging us to do crossover, but then on the other hand, not letting us adjust for the crossover when we do the OS analysis. So now we're in -- I think companies across the industry are in a little bit of a conundrum as to how to manage that, and we're certainly planning on navigating that. So VISION is fully in the label. PSMAfore, a really well-conducted study that we're going to now take forward at the 75% information fraction.

現在我們必須處理的是，一方面，FDA 鼓勵我們進行交叉，但另一方面，在我們進行 OS 分析時，又不允許我們針對交叉進行調整。所以現在我們正處於——我認為整個行業的公司在如何管理這個問題上都遇到了一些難題，我們當然計劃解決這個問題。因此，VISION 完全體現在標籤中。 PSMAfore，這是一項進行得非常好的研究，我們現在將以 75% 的資訊比例推進該研究。

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馬克·珀塞爾。

It's a question on Kisqali and the outlook. My understanding is that from early next year, there's going to have to be prioritizations behind Ibrance and Kisqali is in the pole position to take hold of that business with the NCCN 1 guideline recommendation.

這是一個關於基斯卡利和前景的問題。我的理解是，從明年初開始，Ibrance 背後必須有優先事項，而 Kisqali 在 NCCN 1 指南建議的支持下處於領先地位，可以掌控該業務。

So your NBRx share on a 3-month rolling basis was 46% in the presentation. How high do you believe that could go given that my understanding is about 1/3 of physicians are still only prescribing Ibrance.

因此，您在簡報中的 3 個月滾動 NBRx 份額為 46%。鑑於我的了解，大約 1/3 的醫生仍然只開 Ibrance 處方，您認為這個數字能達到多高？

And then just a housekeeping question, sticking on Kisqali. You've now hit 500 iDFS events. I was just wondering whether you could communicate if the upper confidence in for an overall survival is fallen below 1.0, it was 1.07 at the 46 iDFS events stage? And if not, your confidence in that reaching scale significance?

然後只是一個內務問題，繼續問基斯卡利。您現在已達到 500 個 iDFS 事件。我只是想知道如果整體存活率的上限置信度低於 1.0（在 46 個 iDFS 事件階段為 1.07），您是否可以溝通？如果沒有，您對達到規模重要性有信心嗎？

Yes. Thanks, Mark. So first, on Kisqali and [NBRx], obviously, it's hard to predict. And we certainly know that the MonarchE program will also read out in OS at some point in time. But nonetheless, we see very strong trends across the board on Kisqali. We think the -- given our superiority the -- or I should say, given their strong OS data across 3 lines versus 1 competitor and the other competitors largely positioned as a second-line therapy after CDK4/6 failure, we're seeing very strong uptake. And we continue to believe we can become the leading -- consistently the leading NBRx player. And most importantly, that to start to translate consistently on TRx share which, of course, is the long term what was going to drive the sales potential.

是的。謝謝，馬克。首先，對於 Kisqali 和 [NBRx]，顯然很難預測。我們當然知道MonarchE程式也會在某個時間點在作業系統中讀出。但儘管如此，我們在 Kisqali 上看到了非常強勁的全面趨勢。我們認為——考慮到我們的優勢——或者我應該說，考慮到他們在3 個系列中與1 個競爭對手相比的強大OS 數據，而其他競爭對手主要定位為CDK4/6 失敗後的二線治療，我們看到非常強烈的吸收。我們仍然相信我們能夠成為領先的——始終是領先的 NBRx 參與者。最重要的是，開始一致地轉換 TRx 份額，當然，從長遠來看，這將推動銷售潛力。

So we don't see any signs at the moment of a slowdown on the trajectory that we -- you saw on that slide. And I would note that we see that trajectory not only in the U.S., but Kisqali now is achieving market leadership for NBRx in our key markets in Europe as well as elsewhere around the world, which I think really demonstrates that the -- in the metastatic setting, we're extremely well positioned for this medicine.

因此，我們目前沒有看到任何放緩跡象，正如您在幻燈片上看到的那樣。我要指出的是，我們不僅在美國看到了這一軌跡，而且 Kisqali 現在正在歐洲以及世界其他地方的關鍵市場中實現 NBRx 的市場領導地位，我認為這確實表明——在轉移性在這種情況下，我們在這種藥物方面處於非常有利的位置。

And as I noted, we believe in the metastatic setting alone you have a multibillion dollar potential. And then, of course, the adjuvant early breast cancer settings would come on top. I can't comment on the details of the -- of course, on the data that will be presented later this year on the full 500 iDFS event. But we're really confident on the data set that we've seen. It's consistent, and I think only continues to support our case that this medicine should be approved in both the intermediate and high-risk settings, and that's what we tend to follow for.

正如我所指出的，我們相信僅在轉移環境中就有數十億美元的潛力。當然，早期乳癌的輔助治療將是最重要的。當然，我無法評論今年稍後將在完整 500 iDFS 活動中提供的數據的細節。但我們對所看到的數據集非常有信心。這是一致的，我認為這只會繼續支持我們的觀點，即這種藥物應該在中危和高風險環境中獲得批准，而這正是我們傾向於遵循的。

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

您的下一個問題來自 TD Cowen 的 Stephen Scala。

There's a lot of momentum in the Novartis business as evidenced in the guidance raises. There's no reason why the momentum would suddenly stall as we begin 2024, yet consensus does show a bit of a slowdown. I assume you think consensus is underestimating the outlook in 2024. So where do you think consensus is misunderstanding the outlook for next year?

正如指導意見的提高所證明的那樣，諾華業務發展勢頭強勁。 2024 年伊始，這股勢頭沒有理由會突然停滯，但共識確實顯示出一些放緩。我認為您認為共識低估了 2024 年的前景。那麼您認為共識在哪裡誤解了明年的前景？

Yes. Thanks, Steve. So we won't provide, of course, any guidance at the moment on 2024. I mean if you just go through some of our key brands, and I actually am not up to speed on the precise numbers for 2024 consensus. As I've learned, it's better to focus on driving the medicines and not to pay too much attention to where consensus is.

是的。謝謝，史蒂夫。當然，我們目前不會提供 2024 年的任何指導。我的意思是，如果您只瀏覽我們的一些主要品牌，實際上我還不太了解 2024 年共識的準確數字。據我所知，最好專注於推動藥物的發展，而不是過度關注共識。

But you look -- look, Entresto has continued momentum. We expect it to continue to grow across our key markets as we outlined. We think Cosentyx being back to growth on the back globally on the back of the HS -- a stronger growth than the back of the HS in IV indications. Kisqali is really on a strong growth trajectory, and we see no indications of that slowing down in the metastatic setting. And it is our intention to use a priority review voucher, assuming that the FDA agrees to accept it and get the early breast cancer indication moving with respect to Kisqali as soon as possible.

但你看，Entresto 的勢頭仍在持續。正如我們所概述的那樣，我們預計它將在我們的主要市場中繼續成長。我們認為，在 HS 的支持下，Cosentyx 在全球範圍內恢復了增長——在靜脈注射適應症方面，其增長比 HS 的增長更強勁。 Kisqali 確實處於強勁的成長軌道上，我們沒有看到轉移環境中成長放緩的跡象。我們打算使用優先審查憑證，假設 FDA 同意接受它，並儘快讓 Kisqali 的早期乳癌適應症轉移。

You've seen Kesimpta with really strong growth. And Kesimpta independent of the revenue adjustment item, very dynamic, 86% growth. And we see, again, no reason for that not to continue as the B-cell class share growth in Kesimpta's share of the B-cell class also grows over time.

您已經看到 Kesimpta 的成長非常強勁。而Kesimpta獨立於營收調整項目，非常有活力，成長86%。我們再次看到，沒有理由不繼續這種情況，因為 Kesimpta 的 B 細胞類別份額的增長也會隨著時間的推移而增長。

Pluvicto, given the patient growth numbers that we see and getting the supply now fully unconstrained and getting the centers back up and running, adding more centers, focusing on demand generation, I think that's an exciting opportunity. And then we'll see, I think Lutathera in the frontline setting. This all just builds our radioligand therapy portfolio for the longer term to drive growth also in next year.

Pluvicto，考慮到我們看到的患者數量增長，現在供應完全不受限制，讓中心恢復運行，增加更多中心，專注於需求的產生，我認為這是一個令人興奮的機會。然後我們就會看到，我認為 Lutathera 處於前線。這一切只是為我們的長期放射配體治療組合奠定了基礎，以推動明年的成長。

And then, of course, Leqvio, Scemblix, iptacopan all have the potential to make meaningful contributions as well. Scemblix, I think it's going to moderate the growth given that the third line setting is starting to get tapped out, but we eventually hope to be able to move it into earlier lines.

當然，Leqvio、Scemblix、iptacopan 也有潛力做出有意義的貢獻。 Scemblix，我認為考慮到第三條線的設置已經開始被淘汰，我認為它的增長將會放緩，但我們最終希望能夠將其轉移到更早的線路中。

Leqvio will be slow and steady, but climbing that cardiovascular curve, which we've proven we know how to do over the years with Diovan, Entresto, Exforge, Lotrel. So we'll keep climbing that curve. And then the opportunity to launch iptacopan in PNH. I would say that launch will be a tougher launch initially, but we believe over time, we can drive iptacopan to be the standard of care in PNH. And then hopefully get the approvals in C3G and IgAN in the later part of the year. So I think that's the profile on those 9 key brands. Harry, anything you wanted to add?

Leqvio 將緩慢而穩定地進行，但會攀登心血管曲線，多年來我們已經透過 Diovan、Entresto、Exforge、Lotrel 證明我們知道如何做到這一點。所以我們將繼續攀登這條曲線。然後有機會在 PNH 推出 iptacopan。我想說，最初的發布將是一個艱難的發布，但我們相信隨著時間的推移，我們可以推動 iptacopan 成為 PNH 的護理標準。然後希望在今年下半年獲得 C3G 和 IgAN 的批准。我認為這就是這 9 個主要品牌的概況。哈利，你還有什麼要補充的嗎？

Yes. Just one comment, of course. One thing we have to watch here together for is, of course, how the currencies are moving. I have mentioned this in my prepared remarks. But as we have outlined on Page 40 of the IR deck, and as you know, we update this every month on our website.

是的。當然，只有一則評論。當然，我們必須共同關注的一件事是貨幣的走勢。我在準備好的發言中已經提到了這一點。但正如我們在 IR 平台第 40 頁上概述的那樣，並且如您所知，我們每個月都會在我們的網站上更新此內容。

In '24, when you look at consensus at the moment, what we see on the in-house, right, is 3% on the top line roughly and then 7% on the bottom line. The FX is at the moment seen as a minus 1% to minus 2% on the top line impact if the currency stay where they are, and minus 3% on the bottom line, given that in the recent weeks and months, the dollar has strengthened.

在 24 年，當你看看目前的共識時，我們在內部看到的，右圖，頂線大致為 3%，底線為 7%。目前，如果貨幣保持在當前水平，匯價將被視為對營收產生負1% 至負2% 的影響，而考慮到最近幾週和幾個月美元的貶值，對營收的影響將是負3%。加強了。

So just 1 element as you model, right, and watch this. And of course, on top of that, we see a little increasing generic and LOE impacts and [excite our] divestment. Again, I don't want to talk down 2024, but we have to carefully model these things. I do expect that we have a continued excellent momentum on our growth drivers, of course.

因此，在建模時只需 1 個元素，對吧，然後觀看這一點。當然，最重要的是，我們看到通用和 LOE 影響有所增加，並[刺激我們]撤資。再說一次，我不想貶低 2024 年，但我們必須仔細模擬這些事情。當然，我確實預計我們的成長動力將繼續保持良好的勢頭。

Go ahead. I think it's one more question.

前進。我認為這還有一個問題。

We will now take our last question for today. And the question comes from Peter Welford from Jefferies.

現在我們將回答今天的最後一個問題。這個問題來自 Jefferies 的 Peter Welford。

A quick, more broader one on radioligand therapies, given we've seen some big competitors potentially trying to get into this area. I'm curious if you can remind us of the barriers to entry that you see you build in this space? And also what your thoughts are in terms of presenting data internally from both the actinium and also potentially using antibodies together with your radioligand rather than just some of the peptides that are currently used in the portfolio.

鑑於我們已經看到一些大型競爭對手可能試圖進入這一領域，這是關於放射性配體療法的快速、更廣泛的療法。我很好奇您能否提醒我們您在這個領域建立的進入障礙？還有您的想法是在內部呈現來自錒的數據，並且還可能將抗體與您的放射性配體一起使用，而不僅僅是目前組合中使用的一些勝肽。

Yes. Thanks, Peter. The first thing, of course, is building up the supply chain. And here, you've got to be able to source the upstream source materials, be able to produce the lutetium and then have the ability to do the manufacturing of a radioligand in a sterile environment. And then have the ability to run that supply chain with 5 days to get it -- or less, actually, it's really 3 days, you have to get it to the physician in their office to be able to administer -- or in their centers to be able to administer.

是的。謝謝，彼得。首先，當然是打造供應鏈。在這裡，您必須能夠取得上游原料，能夠生產镥，然後能夠在無菌環境中製造放射性配體。然後有能力在 5 天的時間內運行該供應鏈 - 或更短，實際上，實際上需要 3 天，你必須將其交給醫生在他們的辦公室或他們的中心進行管理以便能夠進行管理。

This is a major logistical challenge. We've worked on it now for many, many years. We've built up the global supply chain to have really unconstrained supply between our sites in Europe and our 2 sites in the U.S. with plans to add additional sites in Asia and potentially add additional capacity in Europe and the U.S.

這是一個重大的後勤挑戰。我們已經為此努力了很多很多年。我們已經建立了全球供應鏈，以便在我們的歐洲工廠和美國的兩個工廠之間實現真正不受限制的供應，併計劃在亞洲增加更多工廠，並可能在歐洲和美國增加額外產能。

I would also say on the supply side of things, we've invested heavily in semi-automated and automated lines, which puts us at the forefront, we believe, technologically in the industry to produce high volumes of radioligand therapy. So I think that's one piece of the puzzle is really solving that supply chain topic. We've had our bumps along the way. But I think it's not straightforward for a biotech or pharma company that lives in the world of inventories and not -- and having the luxury of having 6 months of inventory on hand to having a medicine that has 0 inventory in which patients and physicians expect the medicine to be delivered on time every time.

我還想說，在供應方面，我們在半自動化和自動化生產線上投入了大量資金，我們相信，這使我們在技術上處於行業的最前沿，可以生產大量的放射性配體治療。所以我認為真正解決供應鏈問題才是難題的一部分。一路走來，我們也曾經有過坎坷。但我認為，對於一家生活在庫存世界中的生物技術或製藥公司來說，這並不是一件容易的事——手頭有 6 個月的庫存，而患者和醫生期望的藥品庫存為零。每次都按時送藥。

So really just-in-time delivery. Second is to build up the expertise to have a broad RLT pipeline. Right now, we have a broad number of agents. We'll be covering that in the upcoming R&D day. We've really built up the clinical trial network and the internal research and technical development expertise to have a portfolio of radioligand therapies.

所以確實是準時交貨。其次是累積專業知識以擁有廣泛的 RLT 管道。目前，我們擁有眾多的代理商。我們將在即將到來的研發日中介紹這一點。我們確實建立了臨床試驗網絡以及內部研究和技術開發專業知識，以擁有放射配體療法的組合。

Of course, we life cycle managed Pluvicto, we've life cycle managed Lutathera. We have our FAPi currently in Phase II studies. We have our (inaudible) in Phase II studies. We have an Integrin. We're moving forward to folate as well as, as you mentioned, working on peptide -- other peptide fab fragment and antibody-based technologies that would allow us to use radioligand with these antibodies, including, I would say, established ADC targets, where if we can get the biology right, there could be the opportunity that radioligand therapies have an improved therapeutic index given the safety profile that we've seen for RLTs versus ADCs.

當然，我們有生命週期管理的 Pluvicto，我們有生命週期管理的 Lutathera。我們的 FAPi 目前處於 II 期研究中。我們有（聽不清楚）第二階段研究。我們有一個整合素。正如您所提到的，我們正在推進葉酸研究，並致力於研究勝肽——其他肽fab 片段和基於抗體的技術，這些技術將使我們能夠將放射性配體與這些抗體一起使用，我想說的是，包括已建立的ADC 目標，如果我們能夠獲得正確的生物學結果，考慮到我們所看到的 RLT 與 ADC 的安全性，放射性配體療法可能有機會提高治療指數。

That's to be proven, but certainly, you have that opportunity when you build out that development portfolio. And then I think third is having the commercial infrastructure to actually be able to deliver this, manage this. It takes IT systems, patient flows and expertise on the ground that we've really consistently now built up around the world. So I think together, these 3 things consistently built with years now of investment and effort give us a substantial lead versus any competitor. But that said, we take competition very seriously. We agree that there are many people now looking at the space, and we have to continue to raise the bar on how we execute to ensure that we remain the leaders in radioligand therapy in the long run.

這有待證明，但當然，當您建立開發組合時，您就有這樣的機會。然後我認為第三是擁有真正能夠交付和管理這一點的商業基礎設施。它需要我們在世界各地持續建立的 IT 系統、病患流程和專業知識。因此，我認為，經過多年的投資和努力，這三件事始終如一地建立起來，使我們相對於任何競爭對手都具有顯著的領先優勢。但話雖如此，我們非常重視競爭。我們同意，現在有很多人正在關注這個領域，我們必須繼續提高我們的執行標準，以確保我們從長遠來看仍然是放射配體治療領域的領導者。

And I think that's the last question. So I appreciate everybody's time today, and we look forward to giving you an update again at the R&D Day. I hope everyone will be able to join and thank you again for your interest in the company. We'll continue to work hard every day to keep delivering value for all of you, our shareholders. All the best.

我認為這是最後一個問題。感謝大家今天抽出時間，我們期待在研發日再次向您提供最新消息。希望大家能夠加入並再次感謝您對公司的關注。我們將繼續每天努力工作，繼續為我們的股東創造價值。一切順利。

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

謝謝。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。