Novartis AG (NVS) 2023 Q4 法說會逐字稿

Good morning and Good afternoon and welcome to Novartis Q4 2023 Results Release Conference Call and live webcast. (Operator Instructions) A recording of the conference call including the Q&A session will be available on our website shortly after the call ends. With that, I would like to hand over to Mr. Samir Shah, Head of Investor Relations. Please go ahead sir.

早上好，下午好，歡迎來到諾華 2023 年第四季業績發布電話會議和網路直播。 （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。接下來，我想將會議交給投資者關係主管 Samir Shah 先生。請先生繼續。

Thank you very much. Good morning and good afternoon, everybody. Thank you again for listening to our full year results and Q4 results. 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.

非常感謝。大家早安，下午好。再次感謝您收聽我們的全年業績和第四季業績。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。

For a description of some of these factors, please refer to the company's Form 20-F and its most recent quarterly results on Form 6-K that, respectively, were filed with and furnished to the U.S. Securities and Exchange Commission. And with that, I'll hand the call to vas.

有關其中一些因素的描述，請參閱該公司分別向美國證券交易委員會提交和提供的 20-F 表格和 6-K 表格中的最新季度業績。就這樣，我將把電話轉給 vas。

Thank you, Samir, and thanks, everyone, for joining today's call. I know it's a busy day with many companies reading out, but we hope to provide you some insights into our Q4 2023 results and also some perspective on the outlook for Novartis in 2024 and beyond.

謝謝薩米爾，也謝謝大家參加今天的電話會議。我知道今天是忙碌的一天，許多公司都在宣讀報告，但我們希望為您提供一些有關 2023 年第四季度業績的見解，以及對諾華 2024 年及以後前景的一些看法。

If we move to the first slide, Slide 4, as you saw in our earnings release this morning, we delivered a strong full year performance with margin expansion and strong innovation momentum with 10 positive Phase III readouts over the course of 2023. As a reminder, our full year guidance at the start of the year was quite a bit lower than where we ended up. And we had multiple earnings upgrades over the course of the year, demonstrating, I think, the strong business momentum we have at the company. Q4 sales up 10%, core operating income was up 13%. And on the full year, we were up 10% on sales and core operating income up 18%, all in constant currency, and Harry will go through this in more detail in a few moments.

如果我們轉到第一張投影片，即幻燈片4，正如您在今天早上的收益發布中看到的那樣，我們實現了強勁的全年業績，利潤率擴張和強勁的創新動力，在2023 年期間有10 個積極的第三階段數據。 ，我們年初的全年指引比最終的目標要低很多。我認為，我們在這一年中多次上調盈利，這表明我們公司擁有強勁的業務勢頭。第四季銷售額成長 10%，核心營業收入成長 13%。全年來看，我們的銷售額成長了 10%，核心營業收入成長了 18%（全部以固定匯率計算），哈利稍後將更詳細地介紹這一點。

We also had the successful spin-off of Sandoz as a really value-creating event for Novartis and our shareholders. We provided our updated 2024 guidance, where we expect to grow mid-single digit and [cropping] expected to grow high single digit. And we've chosen to be prudent with this guidance at this point in time. And then looking to our midterm guidance, which I'll also go through in more detail, we've extended our midterm guidance of 5% constant currency CAGR growth to 2023 to 2028 and continue to hold to our core operating income margin guidance of 40% plus by 2027.

我們也成功分拆了山德士，這對諾華和我們的股東來說是真正創造價值的事件。我們提供了更新後的 2024 年指導，我們預計該增長將達到中個位數，[裁剪]預計將增長高個位數。目前我們選擇謹慎對待這項指導。然後看看我們的中期指導（我也將更詳細地介紹這一點），我們已將固定貨幣複合年增長率增長5% 的中期指導延長至2023 年至2028 年，並繼續堅持我們的核心營業收入利潤率指導為40到 2027 年將增加 %。

So moving to Slide 5. This year was a really critical year for the company because we completed the transformation of Novartis. And we believe really laying a strong foundation for our future growth. Since 2014, we have spun off both Alcon and Sandoz in shareholder-friendly ways. We have exited our OTC stake also in a shareholder-friendly approach in exiting -- creating a new OTC company with GSK and also importantly, exited our Roche stake, completing a $15 billion share buyback and then -- continuing $15 billion share buyback, which is ongoing currently, and we expect to complete by mid-2025. That leaves us as a pure-play innovative medicines company with a margin of 36% on its way to the 40% plus strong free cash flow and a strong innovation engine, which we think positions us well for the long run.

那麼轉到幻燈片 5。今年對公司來說是非常關鍵的一年，因為我們完成了諾華的轉型。我們相信這確實為我們未來的成長奠定了堅實的基礎。自 2014 年以來，我們以有利於股東的方式剝離了愛爾康和山德士。我們還以股東友好的退出方式退出了我們的場外交易股權——與葛蘭素史克創建了一家新的場外交易公司，而且重要的是，退出了我們的羅氏股權，完成了150 億美元的股票回購，然後——繼續進行150 億美元的股票回購，目前正在進行中，我們預計將於 2025 年中期完成。這使得我們成為一家純創新藥品公司，利潤率為 36%，正在朝著 40% 以上的強勁自由現金流和強大的創新引擎邁進，我們認為從長遠來看，這使我們處於有利地位。

So moving to Slide 6. When you look at Q4, most importantly with the underlying growth of our key growth drivers, which grew 40% overall on the quarter, and that growth rate, we expect to continue. That underlying growth is what gives us confidence that we can grow mid-single digit in the coming years and then continue that growth in 2028 and beyond in the mid-single-digit plus range. Combination of these growth drivers as well as strong pipeline productivity puts us, I think, in a strong position to be a consistent grower over the next decade.

因此，轉向幻燈片 6。當您查看第四季度時，最重要的是我們的主要成長驅動力的潛在增長，該季度總體增長了 40％，並且我們預計該增長率將持續下去。這種潛在的成長讓我們有信心在未來幾年實現中個位數成長，然後在 2028 年及以後繼續保持中個位數以上成長。我認為，這些成長動力以及強大的管道生產力的結合使我們處於有利地位，可以在未來十年成為持續的成長者。

And moving to Slide 7. And I want to just walk through each of the brands to give you some perspectives and then look forward to taking your questions. So first, Entresto delivered 31% growth with sales reaching $6 billion, and we're well on track to reach our peak sales goal of $7 billion plus. This growth was both in the U.S. and ex-U.S. geographies. You can see on our weekly TRx, we continue to reach record highs. We had constant currency growth of 27% and 26% in U.S. and ex-U.S. and China and Japan contributed strongly with strong performance with our ongoing hypertension launches.

現在轉到投影片 7。我想簡單介紹每個品牌，為您提供一些觀點，然後期待回答您的問題。首先，Entresto 實現了 31% 的成長，銷售額達到 60 億美元，我們正在順利實現 70 億美元以上的高峰銷售目標。這一增長發生在美國和美國以外地區。地理。您可以在我們的每週 TRx 中看到，我們繼續創下歷史新高。我們在美國和美國以外地區的貨幣成長率分別為 27% 和 26%。中國和日本在我們持續推出的高血壓產品中表現強勁，並做出了巨大貢獻。

So going -- looking forward, we expect continued growth for this brand. We maintain our guidance on for forecasting purposes that in Entresto LOE would not occur until 2025. And we also maintain our guidance on EU regulatory data protection to November 2026.

因此，展望未來，我們預計品牌將持續成長。出於預測目的，我們維持對 Entresto LOE 直到 2025 年才會發生的指導。我們也將對歐盟監管資料保護的指導維持至 2026 年 11 月。

So moving to Slide 8. Now, Cosentyx reached $5 billion in 2023. And we expect to see at least mid- to high single-digit growth in 2024 on our way to our guidance of $7 billion peak sales. Going a little deeper into this performance, we saw a 17% growth in the U.S. and 26% outside the U.S. This was in part in the U.S. due to revenue deduction adjustments we had in the prior year leading to a lower [base.] But we are seeing very good momentum on our IV and hidradenitis launches in the U.S. and in [hidradenitis] in Europe, which gives us confidence that Cosentyx can be a dynamic grower over the coming years. We'll continue to keep you updated on how these launches progress over the coming quarters. And then we also will keep you updated as well on the 3 ongoing Phase III studies we are progressing in giant cell arteritis, PMR and rotator cuff tendinopathy.

現在轉到投影片 8。現在，Cosentyx 將於 2023 年達到 50 億美元。我們預計 2024 年至少會出現中高個位數成長，朝著 70 億美元峰值銷售額的目標邁進。更深入研究這一業績，我們發現美國增長了 17%，美國以外增長了 26%。這部分是由於我們在上一年進行的收入扣除調整導致[基數]較低。我們看到我們在美國和歐洲的IV 和hidradenitis 上市勢頭非常好，這讓我們相信Cosentyx 在未來幾年可以成為一個充滿活力的成長者。我們將繼續向您通報未來幾季這些發布的進度。然後，我們也將隨時向您通報我們正在鉅細胞動脈炎、PMR 和肩袖肌腱病變方面正在進行的 3 項 III 期研究的最新情況。

So moving to Slide 9. [Kesimpta] sales in the full year doubled to $2.2 billion. We remain on track to reach our $4 billion peak sales guidance, strong growth in the U.S., but also now increasing growth in Europe and in the ex-U.S. market. We currently see 85,000 patients treated with Kesimpta to date. Our U.S. growth is 48% in constant currencies, ex U.S. at 193%. And we have NBRx leadership now in 7 out of 10 major markets outside of the United States. I think everyone knows well the compelling profile we have in terms of efficacy and convenience as well as the easy-to-use (inaudible) that patients can benefit from with Kesimpta. We have 5 years of efficacy, safety and tolerability, and we'll look forward to continuing to expand this brand, both in terms of the growth of the B-cell class in MS, but also increasing our NBRx share within the B-cell class as a key growth driver.

現在轉到投影片 9。[Kesimpta] 全年銷售額翻了一番，達到 22 億美元。我們仍有望實現 40 億美元的高峰銷售指導，美國市場強勁成長，而且歐洲和美國以外地區的成長也正在加快。市場。迄今為止，我們已有 85,000 名患者接受 Kesimpta 治療。以固定匯率計算，我們在美國的成長率為 48%，美國除外為 193%。目前，我們在美國以外 10 個主要市場中的 7 個都處於 NBRx 領先地位。我想每個人都非常清楚我們在功效和便利性方面的引人注目的特點，以及患者可以從 Kesimpta 中受益的易於使用（聽不清楚）的特點。我們擁有 5 年的功效、安全性和耐受性，我們期待繼續擴大這個品牌，無論是在 MS 中 B 細胞類別的增長方面，還是在 B 細胞中增加我們的 NBRx 份額階級作為關鍵的增長動力。

Moving to Slide 10. Now Kisqali reached $2.1 billion in the metastatic breast cancer setting. We maintained our $4 billion peak sales guidance in the metastatic breast cancer setting alone. You can see this growth again was driven by both the U.S. and our international business. Our rolling NBRx share in the metastatic setting is now up to 46%, and we see continued strong growth in the metastatic setting. This is driven by the statistically significant OS. We have now across 3 pivotal studies, the NCCN Category 1 designation, and the median OS of 5 years we've demonstrated across those 3 pivotal trials. We can confirm that we have filed in the EU, U.S. and China, the adjuvant indication across intermediate and high-risk breast cancer, and we'll look forward to keeping you up to speed as we progress towards hopefully, those approvals and launches over the course of this year.

轉向幻燈片 10。現在，Kisqali 在轉移性乳癌領域的投資達到了 21 億美元。僅在轉移性乳癌領域，我們就維持了 40 億美元的高峰銷售指引。您可以看到這種成長再次受到美國和我們的國際業務的推動。我們在轉移性環境中的滾動 NBRx 份額現已高達 46%，我們看到在轉移性環境中持續強勁增長。這是由統計上顯著的作業系統所驅動的。我們現在擁有 3 項關鍵研究、NCCN 1 類指定，以及我們在這 3 項關鍵試驗中證明的 5 年中位 OS。我們可以確認，我們已經在歐盟、美國和中國提交了針對中高風險乳癌的輔助適應症申請，我們期待著讓您及時了解我們在這些批准和上市方面取得的進展。今年的歷程。

Now moving to Slide 11. (inaudible) our full year sales closed out a near blockbuster status at $980 million. Importantly now, we see unconstrained supply for this brand. We maintain our multibillion-dollar peak sales guidance for the current indication. And I can say we see very strong demand signals and growth dynamics in January, consistent with our expectations, but as we clear the supply constraints and some of the challenges we saw in quarter 4, we would get back to strong robust growth in quarter 1, 2024, and what we would expect is robust quarter-on-quarter growth over the course of this year. Some more details in terms of treatment sites. We have over 300 U.S. sites now that are active and regularly ordering, fully unconstrained supply, we're 99.9% now doses injected on the plan today with a capacity of 250,000 radioligand therapy doses expected in 2024 with the approval now of our Indianapolis site. We have a network expansion ongoing to prepare for launches in Asia with announced investments in both China and Japan. And as I already noted, we expect robust quarter-on-quarter growth over the course of 2024. Our PSMA 4 expected U.S. submission is second half 2024, and we'll keep you updated as we progress towards that. And we also remain on track on our -- both our PSMA addition and PSMA localized oligometastatic disease trials to move [Flavio] into earlier lines of therapy.

現在轉到投影片 11。（聽不清楚）我們的全年銷售額達到了 9.8 億美元，近乎重磅。現在重要的是，我們看到這個品牌的供應不受限制。我們維持當前適應症數十億美元的高峰銷售指引。我可以說，我們在一月份看到了非常強勁的需求訊號和成長動力，這與我們的預期一致，但隨著我們清除供應限制和我們在第四季度看到的一些挑戰，我們將在第一季度恢復強勁成長，2024 年，我們預計今年將出現強勁的季度環比成長。有關治療部位的更多細節。我們現在在美國擁有300 多個站點，這些站點處於活躍狀態，定期訂購，供應完全不受限制，目前計劃中的劑量已註射99.9%，隨著我們印第安納波利斯站點現已獲得批准，預計2024年可容納250,000 劑放射配體治療劑量。我們正在進行網路擴張，為在亞洲推出做準備，並已宣佈在中國和日本進行投資。正如我已經指出的，我們預計 2024 年將出現強勁的季度環比增長。我們的 PSMA 4 預計將於 2024 年下半年在美國提交，隨著我們的進展，我們將隨時向您通報最新情況。我們也繼續進行我們的 PSMA 添加和 PSMA 局部寡轉移疾病試驗，以將 [Flavio] 轉移到早期的治療方案。

Now moving to Slide 12. Scemblix had a strong year and strong quarter, moving up now to $125 million in quarter 4, 2023 and this is in the third line setting where we have leading third line market share, NBRx share of 43%, TRX share of 22%. I think as you all well know, there's high unmet need in the third line setting and over 50% of hematologists really want improvements in quality of life and better management of side effect. And some of it really delivers that. Now we have 4 years of follow-up that really demonstrated differentiated profile in terms of efficacy as well as a very clear and strong safety profile. So the global rollout in the third line setting is ongoing. We have approval in over 60 markets. We have access granted now in over 25 markets and very positive feedback from payers on the clinical benefit.

現在轉到幻燈片12。Scemblix 經歷了強勁的一年和強勁的季度，目前在2023 年第四季度達到1.25 億美元，這是在第三線設置中，我們擁有領先的第三線市場份額，NBRx 份額為43%，TRX佔22%。我想大家都知道，三線治療的需求尚未得到滿足，超過 50% 的血液科醫生確實希望改善生活品質並更好地管理副作用。其中一些確實做到了這一點。現在我們進行了 4 年的隨訪，真正證明了在功效方面的差異化特徵以及非常清晰和強大的安全性。因此，第三線設置的全球推廣正在進行中。我們已獲得 60 多個市場的批准。我們現已在超過 25 個市場獲得准入資格，付款人對臨床效益給予了非常正面的回饋。

Now moving to Slide 13. We read out earlier this month, the ASC4FIRST trial, which met both its primary endpoints with clinically meaningful and statistically significant results in the frontline setting for Scemblix. As a reminder, this study had Scemblix compared to investigator choice TKI. We estimate 50% of the patients were on imatinib and 50% of the patients were on second-gen TKI, [nilotinib or dasatinib or bosutinib.] Both primary endpoints were met. We showed superior major molecular response rates at week 48 for standard of care. And we also had a very favorable safety and tolerability profile with fewer EAEs, treatment discontinuation and and no new safety signals observed. So we're very excited about this data. Importantly, MMR is a good predictor, a reasonable predictor of important endpoints such as PFS, OS and EFS. So this data will be presented at an upcoming medical Congress. We're moving rapidly towards a submission in the first half of 2024, and we'll look forward to sharing this full data set and really providing our conviction that Scemblix can be a multibillion-dollar medicine for Novartis.

現在轉到幻燈片 13。本月早些時候，我們宣讀了 ASC4FIRST 試驗，該試驗在 Scemblix 的一線環境中達到了兩個主要終點，並獲得了具有臨床意義和統計顯著性的結果。提醒一下，本研究將 Scemblix 與研究者選擇的 TKI 進行了比較。我們估計 50% 的患者服用伊馬替尼，50% 的患者服用第二代 TKI，[尼洛替尼或達沙替尼或博舒替尼]。兩個主要終點均已滿足。我們在第 48 週時對標準護理表現出優異的主要分子緩解率。我們還具有非常良好的安全性和耐受性，EAE 較少，治療中斷較少，也沒有觀察到新的安全訊號。所以我們對這些數據感到非常興奮。重要的是，MMR 是一個很好的預測因子，是 PFS、OS 和 EFS 等重要終點的合理預測因子。因此，這些數據將在即將召開的醫學大會上公佈。我們正在迅速爭取在 2024 年上半年提交，我們將期待分享這個完整的數據集，並真正讓我們相信 Scemblix 可以成為諾華價值數十億美元的藥物。

Now moving to Slide 14. Leqvio continued its steady expansion in the U.S. as well as across regions. You can see here, we delivered $123 million on the quarter growth in both our international and our U.S. business. On the U.S. side, we have 3,500 facilities now ordering Leqvio, which is a 13% growth versus quarter 3. 55% of that business now is coming from in-office buy and bill. And we expect to continue to drive growth on this brand by driving depth in our key accounts as well as expanding the buy-and-bill acquisition channel. Ex U.S., our rollout also continues well with 29 countries with public reimbursement, 39 countries with private coverage, and we see very positive solid early signals in China in the self-pay market which we expect to continue over the course of 2024 ahead of a proposed [NRDL] listing in 2025. In terms of the outcome trials, we remain on track for our secondary prevention outcome studies in 2026. And and we also continue to enroll our primary prevention studies as well.

現在轉到投影片 14。Leqvio 繼續在美國以及跨地區穩步擴張。您可以在這裡看到，我們的國際和美國業務本季實現了 1.23 億美元的成長。在美國方面，我們現在有 3,500 家工廠訂購 Leqvio，與第三季相比成長了 13%。目前該業務的 55% 來自辦公室內購買和帳單。我們預計將透過提高關鍵客戶的深度以及擴大購買和帳單獲取管道來繼續推動該品牌的成長。除美國外，我們的推廣工作也在29 個提供公共報銷的國家和39 個提供私人保險的國家中繼續順利開展，我們在中國的自費市場中看到了非常積極、可靠的早期信號，我們預計這一訊號將​​在2024 年持續下去，直到擬於2025 年列入[NRDL]。就結果試驗而言，我們仍將在2026 年進行二級預防結果研究。而且我們也持續招募我們的一級預防研究。

And moving to Slide 15. Fabhalta now has launched in the United States, and we see, I think, very positive early launch signals, but we do expect a modest ramp for this brand given the dynamics within the PNH market. As a reminder, we have very compelling data for this medicine, including improvements in hemoglobin transfusion avoidance, IVH, intravascular and extravascular hemolysis control and a very clean safety profile. Our populations in our label are both -- are adults with PNH, both naive and switch patients which was our target label for this medicine. And with -- as an oral therapy, we think we really provide a unique offering for patients with PNH. There is a REMS requirement, but this is similar to other complement inhibitors. Right now, as we look at our launch, our focus very much is coming out of ASH, getting patients up on our patient support program, getting our REMS up and running. Our first patients have already been initiated. And what we're hearing is positive HCP sentiment and interest from patients and payer groups. And our goal will be initially to focus on newly diagnosed patients as well as patients who are not currently under full control for their hemolysis with their existing therapies. Over time, we would want to certainly expand this market. We estimate half of patients with PNH are currently not on therapy. And with an oral agent, we have the possibility, we hope, over time, to get more patients on therapy to avoid any of the subsequent sequela associated with PNH.

轉到幻燈片 15。Fabhalta 現在已在美國推出，我認為我們看到了非常積極的早期推出信號，但考慮到 PNH 市場的動態，我們確實預計該品牌將出現適度的增長。提醒一下，我們對該藥物有非常令人信服的數據，包括避免血紅蛋白輸血、IVH、血管內和血管外溶血控制以及非常清晰的安全性方面的改善。我們標籤中的人群都是患有 PNH 的成年人，既有初治患者，也有轉換患者，這是我們該藥物的目標標籤。作為一種口服療法，我們認為我們確實為 PNH 患者提供了獨特的產品。有 REMS 要求，但這與其他補體抑制劑類似。現在，當我們看到我們的發佈時，我們的重點是 ASH，讓患者參與我們的患者支援計劃，讓我們的 REMS 啟動並運行。我們的第一批患者已經開始接受治療。我們聽到的是醫護人員的正面情緒以及病人和付款人團體的興趣。我們的目標最初是關注新診斷的患者以及目前無法透過現有療法完全控制溶血的患者。隨著時間的推移，我們肯定希望擴大這個市場。我們估計一半的 PNH 患者目前沒有接受治療。透過口服藥物，我們希望隨著時間的推移，有可能讓更多患者接受治療，以避免任何與 PNH 相關的後續後遺症。

Now moving to Slide 16. As noted in 2023, we had 10 positive Phase III readouts with significant sales potential. You see them listed here. A lot of this data will be presented over the course of 2024. So you'll have a better understanding of the potential of these medicines whether it's medicines like remibrutinib. We've already seen the Lutathera NETTER-2 data, which I think is really outstanding. And hopefully, some of you saw that potential now for Lutathera front line setting. Of course, the data for Atrasentan and Iptacopan and the Scemblix data, which I've already mentioned.

現在轉到投影片 16。正如 2023 年所指出的，我們有 10 個具有巨大銷售潛力的正面的 III 期資料。您會看到它們列在這裡。大量此類數據將在 2024 年期間提供。因此，您將更了解這些藥物的潛力，無論是瑞米替尼等藥物。我們已經看到了 Lutathera NETTER-2 的數據，我認為它非常出色。希望你們中的一些人現在看到了 Lutathera 前線設置的潛力。當然，還有我已經提到的 Atrasentan 和 Iptacopan 的數據以及 Scemblix 的數據。

So moving to Slide 17. I just want to say a word of some of the top line readouts we had in quarter 4. Iptacopan had another -- it's a third Phase III readout with -- a positive Phase III readout with clinically meaningful in statistically significant proteinuria reduction in patients with C3G [Lumara] nephropathy. You see here on the left, the Phase II data, which we previously disclosed in Phase III, we had a study design versus placebo, looking at month 6 before patients crossed over to Iptacopan on both arms. We saw this really important proteinuria reduction and safety profile consistent with what we've seen in previous data, and we're currently engaged with regulatory agencies with a goal for submissions in 2024.

所以轉向幻燈片17。我只想說我們在第四季度獲得的一些最重要的讀數。Iptacopan 還有另一個- 這是第三個III 期讀數- 一個積極的III 期讀數，在統計上具有臨床意義C3G [Lumara] 腎臟病患者的蛋白尿顯著減少。您可以在左側看到 II 期數據，我們之前在 III 期中披露過，我們有一項研究設計與安慰劑對比，觀察患者雙臂交叉使用 Iptacopan 之前的第 6 個月。我們看到這非常重要的蛋白尿減少和安全性與我們在先前的數據中看到的一致，我們目前正在與監管機構合作，目標是在 2024 年提交申請。

And moving to Slide 18. Over the course of the year, we had positive readouts both on iptacopan and our newly acquired atrasentan in IgA nephropathy, clinically meaningful results here as well. Both of these programs have been reviewed with the FDA and we're on track for submissions of these medicines that would really allow us to have, I think, a robust portfolio of medicines to bring to nephrologists in IgA nephropathy and then in the future C3G as we continue to try to build out a nephrology presence around the world. The Zigakibart, our anti-APRIL antibody, also acquired in the (inaudible) acquisition , is also on track in its Phase III study.

轉到幻燈片 18。在這一年中，我們對 iptacopan 和我們新獲得的阿曲生坦治療 IgA 腎病的結果均呈陽性，這也是具有臨床意義的結果。這兩個項目都已經過 FDA 的審查，我們正在按計劃提交這些藥物，我認為這將真正使我們能夠擁有強大的藥物組合，為 IgA 腎病以及未來的 C3G 腎病專家提供服務我們繼續努力在世界各地建立腎臟科基地。 Zigakibart 是我們的抗 APRIL 抗體，也是在（聽不清楚）收購中獲得的，目前也正在進行 III 期研究。

So moving to Slide 19. Now we expect our innovation momentum to continue in 2024. This will be a year of data readouts, full data readouts and submissions primarily for the company. We expect a few Phase III starts, but importantly, as I mentioned, key data readouts and submissions, we'll keep you posted on as we progress. And when you look at Slide 20, this is where -- why we have confidence as well that we'll have a steady stream of innovation to drive the company's growth beyond 2028. With the number of exciting, I think, assets we have, '24, '25 as well as the '26-'28 time frame. This will create a steady flow replacement power and innovation, enabling us to drive that mid-single-digit growth rate beyond.

現在轉到投影片 19。現在我們預計我們的創新動能將在 2024 年繼續下去。這將是主要針對公司的數據讀出、完整數據讀出和提交的一年。我們預計會有一些第三階段啟動，但重要的是，正如我所提到的，關鍵數據讀出和提交，我們將隨時向您通報進度。當你看幻燈片 20 時，這就是為什麼我們也有信心，我們將有源源不斷的創新來推動公司在 2028 年之後的增長。我認為，憑藉我們擁有的令人興奮的資產數量， '24、' 25 以及'26-'28 時間範圍。這將創造穩定的替代動力和創新，使我們能夠推動中個位數的成長率。

Now moving to Slide 21. Over the course of the year, we also signed 15 strategic deals, exits as well as acquisitions totaling over $6 billion. I do want to emphasize our core approach in M&A remains as bolt-on acquisitions in the sub-$5 billion space. Deals such as Chinook, but also many smaller deals you can see across the full landscape. We're very much focused on technologies like exRNA, gene therapy and RLT as well as our key therapeutic areas like -- such as Chinook amongst others. We also continue to invest in artificial intelligence on top of our collaborations with Microsoft and Palantir. We've also signed an agreement now with Isomorphic Labs of Google's DeepMind, which really allows us, I think, to be partnered with some of the most preeminent AI researchers in the world to speed up our drug discovery and drug development.

現在轉到投影片 21。這一年裡，我們還簽署了 15 項策略交易、退出和收購，總金額超過 60 億美元。我確實想強調，我們在併購方面的核心方法仍然是在 50 億美元以下的領域進行補強收購。諸如奇努克之類的交易，以及您在整個景觀中都可以看到的許多較小的交易。我們非常關注 exRNA、基因治療和 RLT 等技術，以及 Chinook 等關鍵治療領域。除了與微軟和 Palantir 的合作之外，我們還繼續投資人工智慧。我們現在也與Google DeepMind 的同構實驗室簽署了一項協議，我認為這確實使我們能夠與世界上一些最傑出的人工智慧研究人員合作，以加快我們的藥物發現和藥物開發。

Now moving to Slide 22. We did also today extend and update our midterm guidance. You'll remember at R&D Day, we had noted '22 to '27, 5% CAGR. And today, given the momentum we're seeing on our growth drivers and the strong pipeline performance we're seeing, we're extending that 5% growth guidance to '23 to '28. Now of course, up until '28, we do have some Gx impact, which I'm sure we can discuss further in the Q&A. But the momentum we're seeing in our in-market growth drivers across our base business across each of the brands, which I've already discussed as well as the positive data that we've seen in (inaudible) remibrutinib and atrasentan gives us confidence now that we can continue that 5% growth up to '28. And as we've already guided mid-single digits beyond that.

現在轉到幻燈片 22。今天我們還擴展並更新了我們的中期指導。您會記得在研發日，我們注意到 22 至 27 年複合年增長率為 5%。今天，鑑於我們看到的成長動力的勢頭以及我們看到的強勁的管道業績，我們將 5% 的成長指引延長至 23 年至 28 年。當然，直到 28 年，我們確實對 Gx 產生了一些影響，我相信我們可以在問答中進一步討論。但我們在每個品牌的基礎業務中看到的市場成長動力的勢頭，我已經討論過，以及我們在（聽不清楚）瑞米布替尼和阿曲生坦中看到的積極數據給了我們現在我們有信心能夠繼續保持 5% 的成長直至 28 年。正如我們已經指導的那樣，這個數字已經超過了中個位數。

So moving to Slide 23. I want to close with just a word on ESG, which remains very much a part of the Novartis' strategy and Novartis' approach. We focus on innovation and access to medicines, human capital in terms of our work on DE&I culture as well as ensuring that we're amongst the leaders in environmental sustainability and ethical standards. When you look at our performance, now we're #1 in Sustainalytics in the Leaders Group in MSCI and also amongst the leaders in important other benchmarks such as access to medicine and CDP. And we plan to continue that, of course in 2024. And so with that, on Slide 24, I'll hand it over to Harry.

現在轉到投影片 23。我想以 ESG 一詞作為結束，它仍然是諾華策略和諾華方法的重要組成部分。我們在 DE&I 文化工作中專注於創新和藥品取得、人力資本，並確保我們在環境永續性和道德標準方面處於領先地位。如果您看看我們的表現，現在我們在 MSCI 領導者組中的 Sustainalytics 方面排名第一，並且在其他重要基準（例如藥物獲取和 CDP）方面也名列前茅。當然，我們計劃在 2024 年繼續這樣做。因此，在幻燈片 24 上，我將把它交給 Harry。

Yes. Thank you very much, Vas. Good morning and good afternoon, everybody. I'm now going to walk you through some of the financials for the fourth quarter and full year as well as provide you with our 2024 guidance. As always, my comments refer to growth rates in constant currencies, unless I would otherwise note that. Also throughout the presentation, I'm only going to talk about continuing operations. And just as a reminder, that continuing operations include retained business activities of Novartis, comprising of our Innovative Medicines business and the continued corporate activities. (inaudible) operations include Sandoz and selected portions of corporate activities attributable to the Sandoz business as well as certain expenses related to the spinoff.

是的。非常感謝你，瓦斯。大家早安，下午好。我現在將向您介紹第四季度和全年的一些財務數據，並向您提供我們的 2024 年指引。像往常一樣，我的評論指的是固定匯率計算的成長率，除非我另外指出。在整個演示過程中，我也只會談論持續營運。提醒一下，持續經營包括諾華保留的業務活動，包括我們的創新藥物業務和持續的企業活動。 （聽不清楚）業務包括 Sandoz 和屬於 Sandoz 業務的選定部分公司活動以及與分拆相關的某些費用。

Next slide, please. This chart shows you the restated comparable numbers post the Sandoz spinoff. I know history doesn't tell the future, but track record is important. And as you can see, since 2018, top line sales growth has been 7% in average; bottom line, even 14% CAGR, and this has resulted in a core margin increase of 990 basis points in constant currency to 36%. So a very clear path also from a margin standpoint to our 40% in 2027. This strong performance has continued in '23, where we met or even slightly exceeded our upgraded full year guidance.

請下一張投影片。這張圖表向您展示了山德士分拆後重述的可比較數字。我知道歷史並不能預示未來，但過往記錄很重要。正如您所看到的，自 2018 年以來，營收平均成長率為 7%；底線，複合年增長率甚至為 14%，這導致核心利潤率以固定匯率計算增加了 990 個基點，達到 36%。因此，從利潤率的角度來看，到2027 年，我們的利潤率將達到40%，這也是一條非常清晰的道路。這種強勁的表現在2023 年持續存在，我們達到甚至略微超過了升級後的全年指導。

On the next slide, yes, just a little comparison here. On the '23 shows the top line growth of 10%. We guided to grow basically high single digits, last one, but we upgraded 3 times through the year and we started with a low to mid-single digit, really a testimony to the excellent business momentum that even strengthened throughout the year. And then core operating income at 18% and again, here, we could -- we were able to upgrade 3 times. And could even slightly exceed the guidance we gave in October of mid- to high teens.

在下一張投影片上，是的，這裡只是進行一些比較。 '23 年的收入成長了 10%。最後一個目標是基本上實現高個位數成長，但我們全年升級了 3 次，並且從低到中個位數開始，這確實證明了全年甚至增強的出色業務勢頭。然後核心營業收入達到 18%，我們可以—我們能夠升級 3 倍。甚至可能略高於我們在 10 月給出的中高青少年的指導值。

On Slide 27, a bit more detail about the 2023 performance, which I will go through by quarter and full year. On the quarter, top line growth was 10%. Core operating income grew 13%. As outlooked in October, quarter 4 of '22 was very high profit quarter to be compared to given that we were in the middle of our restructuring then, and that's why we guided the full year to where we were already assuming that quarter 4 bottom line growth would be a little bit less than the 9-month bottom line growth. But still resulting in a margin improvement of 1 percentage point and core EPS at $1.53. And so a good quarter.

在投影片 27 上，詳細介紹了 2023 年的業績，我將按季度和全年進行介紹。本季營收成長 10%。核心營業收入成長13%。正如 10 月的展望，相比之下，22 年第 4 季的利潤非常高，因為當時我們正處於重組中期，這就是為什麼我們將全年指導方針設定為我們已經假設的第 4 季的底線成長將略低於9 個月的底線成長。但仍導致利潤率提高 1 個百分點，核心每股收益達 1.53 美元。這是一個不錯的季度。

For full year, top line grew 10% and for core operating income, we delivered 18%, leading to a 2.4 percentage points margin increase. Core EPS was $6.47. And the full year cash flow was even more than $13 billion, another significant growth also on the cash flow side. As outlooked, therefore, we were over our guidance and strong full year results with also a strong quarter in absolute but of course, comparable base was a bit higher.

全年營收成長 10%，核心營業收入成長 18%，利潤率提高 2.4 個百分點。核心每股收益為 6.47 美元。全年現金流甚至超過130億美元，現金流方面也出現了顯著成長。因此，正如預期的那樣，我們超越了我們的指導和強勁的全年業績，絕對值也表現強勁，但當然，可比基數略高。

Now Slide 28. So we're continuing to create significant and sustainable shareholder value. As you know, we are a highly cash-generative business, and our strong cash flow allows us to optimize both investing in the business as well as returning capital to shareholders. In terms of investing in the business, of course, R&D is the key focus, in addition to launch and prelaunch investments. And from a business development, M&A perspective, it is value-creative bolt-ons in our core therapeutic areas. In terms of returning capital to our shareholders, the focus has been on a consistent growing annual dividend in Swiss francs which has not been rebased post the [Alcon and the Sandoz] spin-off. And with regards to share buybacks, we continue, of course, our most recent share buyback of up to $15 billion announced in July 2023 with up to $12.7 billion to be executed still by the end of 2025. Now we got some questions as we paused share buyback for a few weeks in January as we had to adjust our trading plan. Just to ensure everybody is clear, we will restart during the next days and it's our full intention to complete that share buyback as mentioned by the end of 2025. Besides all of that, we have, of course, also created shareholder value through numerous strategic actions like divesting the consumer healthcare joint venture stake, spinning off Alcon, and divesting the Roche stake at [CHF 356] and of course, importantly, and most recently, the successful completion of the spin of Sandoz on October 4 last year.

現在看投影片 28。因此，我們將繼續創造重大且可持續的股東價值。如您所知，我們是一家高度產生現金的企業，強大的現金流使我們能夠優化業務投資以及向股東返還資本。在業務投資方面，除了啟動和啟動前的投資外，研發當然是重點。從業務發展、併購的角度來看，它是我們核心治療領域的價值創造補充。在向股東返還資本方面，重點是瑞士法郎年度股息的持續增長，在[愛爾康和山德士]分拆後，該股息並未重新調整。至於股票回購，我們當然會繼續我們在 2023 年 7 月宣布的最近一次股票回購，回購金額高達 150 億美元，到 2025 年底仍將執行高達 127 億美元。現在我們暫停時遇到了一些問題由於我們不得不調整我們的交易計劃，因此在一月份進行了幾週的股票回購。為了確保每個人都清楚，我們將在接下來的幾天內重新啟動，我們完全打算在2025 年底之前完成所提到的股票回購。除此之外，當然，我們還透過眾多策略性舉措創造了股東價值諸如剝離消費者醫療保健合資企業股權、分拆愛爾康以及以[356 瑞士法郎]剝離羅氏股份等行動，當然，最重要的是，最近，去年10 月4 日成功完成了山德士的分拆。

If we go to the next slide, please. Now talking about the successful spin-off of Sandoz. On the day of the spin and subsequently, both Novartis as well as Sandoz share price and the implied market capitalization have increased quite significantly. Since the day of the spin off, October 4 until yesterday, just to have the exact numbers from last night's closing, Novartis market cap has increased by over 11% and Sandoz over 28%. So in total, as a result of the spin-off and of course, (inaudible) market movements, a combined value of over $28 billion has been created for shareholders, continuing to hold Novartis and Sandoz share. Again, as a reminder, we are not rebasing our dividend post the Sandoz spin. Speaking of the dividend, let's go to the next page. Yes, we are pleased to propose the 27th consecutive dividend increase to CHF 3.30 per share and USD even $3.92. And this is based on the CHF 3.20 last year. So an increase of 3% in Swiss francs and 12% in U.S. dollars with a dividend yield reaching close to 4%. And it's fully in line with our policy of increasing our dividend every year in Swiss francs per share without rebasing and post-Sandoz spin.

請轉到下一張投影片。現在談談山德士的成功分拆。分拆當天及隨後，諾華和山德士的股價以及隱含市值均大幅上漲。自分拆之日起，即 10 月 4 日至昨天，僅從昨晚收盤的確切數據來看，諾華的市值已增長超過 11%，山德士的市值已增長超過 28%。因此，總的來說，由於分拆，當然還有（聽不清楚）市場波動，為股東創造了超過 280 億美元的總價值，繼續持有諾華和山德士的股份。再次提醒大家，山德士分拆後我們不會重新調整股利基數。說到股息，我們進入下一頁。是的，我們很高興提議連續 27 次將股息提高至每股 3.30 瑞士法郎，甚至 3.92 美元。這是基於去年的 3.20 瑞士法郎。因此，瑞士法郎上漲 3%，美元上漲 12%，股息殖利率接近 4%。這完全符合我們每年增加每股瑞士法郎股息的政策，而無需重新設定基準和山德士之後的重組。

Now moving to 2024. Our full year guidance is for sales to grow mid-single digit and core operating income to grow high single digit. In terms of the drivers of core OpInc for 2024, pushes and tools are similar to 2023, and we fully expect our positive business momentum to continue. However, this prudent guidance assumes that there will be a higher generic impact in 2024 versus 2023. I'm sure you will discuss this later on in the Q&A. For forecasting purposes, we assume no U.S. Entresto generic entry in 2024. And to complete our full year 2024 guidance, please note that we expect core net financial expenses to be around $0.6 billion to $0.7 billion and the core tax rate to be around 16% to 16.5%.

現在進入 2024 年。我們的全年指引是銷售額實現中個位數成長，核心營業收入實現高個位數成長。就 2024 年核心 OpInc 的驅動因素而言，推動力和工具與 2023 年類似，我們完全預期我們積極的業務動能將持續下去。然而，這項謹慎的指導假設 2024 年將比 2023 年產生更高的一般影響。我相信您稍後會在問答中討論這一點。出於預測目的，我們假設2024 年不會有美國Entresto 仿製藥上市。為了完成我們的2024 年全年指引，請注意，我們預計核心淨財務費用約為6 億至7 億美元，核心稅率約為16%至 16.5%。

Now on to my final slide. There we go. Currencies, yes. So we have outlined some details regarding the currency impact. And as you can see, currencies had a negative 2 points impact on net sales in both quarter 4 and the full year as well as negative 8 points impact on core operating income for the quarter 4 and negative 7 points for the full year, driven by the strong Swiss franc. There was a special effect on core OpInc in quarter 4 by about 2 points due to the mid-December Argentina devaluation and then we have to catch up basically to hyperinflation accounting instructions, IFRS guidelines, the full effect in quarter 4. So it's 2 points worsening due to Argentina in quarter 4. If late January rates prevail for 2024, we expect a full year impact of currencies to be less than ['23.] And on top line would be a negative 1 percent and on the bottom line, would be a negative 3 percentage points currency impact. And as a reminder, we do update this every month on our website as it is hard to forecast from the outside, but you get a monthly update on it. And with that, I hand back to Vas.

現在開始我的最後一張投影片。我們開始吧。貨幣，是的。因此，我們概述了有關貨幣影響的一些細節。正如您所看到的，貨幣對第4 季和全年的淨銷售額產生了2 個百分點的負面影響，對第4 季和全年的核心營業收入產生了8 個百分點的負面影響，對全年產生了7 個百分點的負面影響。堅挺的瑞士法郎。由於12 月中旬阿根廷貨幣貶值，第4 季的核心OpInc 受到了約2 個點的特殊影響，然後我們基本上必須趕上惡性通貨膨脹會計指令、IFRS 指南、第4 季的全部影響。所以是2個點由於第 4 季阿根廷的影響，情況惡化。如果 2024 年 1 月下旬的利率占主導地位，我們預計貨幣對全年的影響將小於 ['23]。頂線將是負 1%，底線是貨幣匯率將受到3 個百分點的負面影響。提醒一下，我們每個月都會在我們的網站上更新此訊息，因為很難從外部預測，但您會收到每月更新。說完，我把話交還給瓦斯。

Great. Thank you, Harry. So in conclusion, if we could go to Slide 34, we had a very strong 2023 multiple guidance increases, double-digit growth for sales and core OpInc. I think really reflecting that our focused strategy as a pure-play innovative medicines company is the right one and really delivering strong operational performance. We met or exceeded our strategic operational and innovation targets, including the successful Sandoz spin-off, 10 positive Phase III readouts, all with significant sales potential. And we're confident for 2024 and in the midterm, where we now guide to 5% constant currency sales, '23 to '28 and a 40%-plus margin in 2027, all building, of course, on the longer-term goal to maintain that mid-single-digit sales growth '28 and beyond.

偉大的。謝謝你，哈利。所以總而言之，如果我們可以看幻燈片 34，我們的 2023 年指導成長非常強勁，銷售額和核心 OpInc 實現兩位數成長。我認為這確實反映出我們作為一家純粹的創新藥品公司的重點策略是正確的，並且真正帶來了強勁的營運績效。我們達到或超越了我們的策略營運和創新目標，包括成功分拆山德士、10 個積極的第三階段讀數，所有這些都具有巨大的銷售潛力。我們對2024 年和中期充滿信心，我們現在的目標是23 年至28 年實現5% 的固定貨幣銷售額，並在2027 年實現40% 以上的利潤率，當然，所有這些都建立在長期目標的基礎上28 年及以後維持中個位數的銷售成長。

So with that, we can open the line for questions, as the operator mentioned, we'll limit to one question for analysts, and then we'll come back through the list again. Thank you very much.

這樣，我們就可以開啟問題佇列，正如操作員所提到的，我們將限制分析師提出一個問題，然後我們將再次瀏覽清單。非常感謝。

(Operator Instructions) We will now go to our first question. And your first question comes from the line of Matthew Weston, UBS.

（操作員說明）我們現在討論第一個問題。你的第一個問題來自瑞銀集團的馬修‧韋斯頓。

It's Matt Weston from UBS. My one question is around the growth in SG&A that we saw in 4Q and what it means for 2024 guidance. So there was a significant step-up in commercial spending. Vas, you mentioned in your opening remarks that you felt that 2024 guidance was prudent. Is the 4Q step-up bringing forward or front-loading launch spend given the exciting opportunities you have in '24? Or is that level of [good] indicator of the cost acceleration we should expect for the full year? Any help gratefully received.

我是瑞銀集團的馬特‧韋斯頓。我的一個問題是關於我們在第四季度看到的 SG&A 成長以及這對 2024 年指引意味著什麼。因此，商業支出大幅增加。 Vas，您在開場白中提到，您認為 2024 年的指引是審慎的。鑑於您在 24 年擁有的令人興奮的機會，第四季度的啟動支出是否會提前或提前加載？或者說，這個水準是我們應該預期的全年成本加速的[良好]指標嗎？非常感謝任何幫助。

Thanks, Matthew. I'll hand it over to Harry. Harry?

謝謝，馬修。我會把它交給哈利。哈利？

Hello, Matthew. Good to have you around. I think quarter 4 came exactly in as we forecasted for the year and outlined our full year guidance in October. So I think we have to keep this a bit in perspective and not overreact to short-term consensus thinking. Because in the end, we increased our function costs in the full year like 3% in constant currencies with a growth of 10% on the top line. I tried to explain, maybe I was not very successful in October, that quarter 4 of '22 was a very low spend quarter because we're in the middle of a big restructuring. Now quarter 4 spend is usual seasonality of higher spend levels versus the first 3 quarters. In '22, that was a bit muted, we are back to that normal pattern. So you should have no worries about our cost development for '24. Our guidance of continued margin improvement is absolutely [base] bulletproof because of our top line growth as well as our productivity programs and everything in '23 came in as planned.

你好，馬修。很高興有你在身邊。我認為第四季度的表現完全符合我們對今年的預測，並在 10 月概述了我們的全年指導。所以我認為我們必須正確看待這一點，不要對短期共識思考反應過度。因為最終，我們全年的功能成本增加了 3%（以固定貨幣計算），營收成長了 10%。我試著解釋一下，也許我在 10 月的表現不是很成功，22 年的第四季是支出非常低的季度，因為我們正在進行大規模重組。現在，第四季的支出通常是季節性的，支出水準高於前三個季度。 22 年，情況有點平靜，我們又回到了正常模式。因此，您不必擔心我們 24 年的成本開發。我們對持續利潤率改善的指導絕對是無懈可擊的，因為我們的收入成長以及我們的生產力計劃以及 23 年的一切都按計劃進行。

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安德魯·鮑姆 (Andrew Baum)。

I'm not sure if Dave is on the call, but someone might like to take this question relating to your cardiovascular outcome trials. I've previously asked about why not unblind the ORION-4 particularly given the pressures from the IRA in the 9 years prior to price negotiation. I'd ask the same question about Horizon. These are very high-risk secondary prevention patients. We know that it's highly atherogenic particle. And again, you've got the same issue for 9 years. So is there any possibility of either of these trials being unblinded before the publicly stated dates? And maybe you could also opine on whether the bipartisan assets to try and reclassify advanced therapies for 13 years rather than 9-year exclusivity is going to start to move. It's obviously very relevant to you given Leqvio (inaudible)

我不確定戴夫是否在通話中，但有人可能想回答這個與您的心血管結果試驗有關的問題。我之前曾問過為什麼不解除 ORION-4 的盲目性，特別是考慮到價格談判前 9 年來自 IRA 的壓力。關於地平線，我也會問同樣的問題。這些是非常高危險的二級預防患者。我們知道它是高度致動脈粥狀硬化的顆粒。再說一遍，同樣的問題已經持續 9 年了。那麼，這兩項試驗是否有可能在公開日期之前被揭盲？也許您還可以就嘗試對先進療法重新分類 13 年而不是 9 年獨家權的兩黨資產是否會開始移動發表意見。鑑於 Leqvio，這顯然與您非常相關（聽不清楚）

Yes. Thank you, Andrew. So right now, there's no plans to adjust our thought process on waiting for these studies to run the completion. I think as Dave outlined in the R&D Day, we continue to believe by having a longer follow-up, we're more likely to deliver very differentiated cardiovascular risk reduction in ORION-4. And I think with respect to horizon, our powering calculations and the approach that we've taken both with very high-risk Lp(a) patients as well as the kind of medium risk patients requires us to follow these patients out through 2025. That said, we're very cognizant of your point, and we do debate and discuss them, especially in light of the IRA. I think a few things we're doing. First, on the policy front, there is bipartisan support for an amendment on I think the 9 to 13 on so-called genetically targeted therapies. However, I think it will still be some time and likely not during this year, given it's an election year for that to really move forward. But we're hopeful that we can progress that over the coming years to enable that to move to 9 to 13, along with our broader policy goal as the industry to move 9 to 13 across all small molecules. We also continue to invest in life cycle management for our entire siRNA portfolio. We struck at least a few deals now that really target annual dosing for siRNAs, most recently with a company called Atlantic Therapeutics. And there, we have multiple targets now that we're pursuing to try to move to annual dosing and/or combinations with other targets that would allow us to life cycle manage in the event that we need to ahead of that 9-year time frame. So those are the approaches we're taking, but we obviously take your feedback seriously and we'll continue to evaluate accordingly. Next question, operator.

是的。謝謝你，安德魯。因此，目前沒有計劃調整我們等待這些研究完成的思考過程。我認為，正如 Dave 在研發日中概述的那樣，我們仍然相信，透過進行更長的隨訪，我們更有可能在 ORION-4 中實現差異化的心血管風險降低。我認為就地平線而言，我們的動力計算以及我們對極高風險 Lp(a) 患者以及中等風險患者採取的方法要求我們對這些患者進行跟踪直至 2025 年。說，我們非常理解你的觀點，我們確實辯論和討論它們，特別是考慮到愛爾蘭共和軍。我認為我們正在做一些事情。首先，在政策方面，兩黨都支持所謂的基因標靶治療的9至13號修正案進行修正案。然而，我認為這還需要一段時間，而且很可能不會在今年，因為今年是選舉年，要真正向前邁進。但我們希望我們能夠在未來幾年內取得進展，使這一數字達到 9 到 13，同時我們更廣泛的政策目標是整個產業將所有小分子的數字從 9 提高到 13。我們也持續投資於整個 siRNA 產品組合的生命週期管理。我們現在至少達成了幾筆真正針對 siRNA 年度劑量的交易，最近一次是與一家名為 Atlantic Therapeutics 的公司達成的。在那裡，我們現在有多個目標，我們正在追求嘗試轉向年度劑量和/或與其他目標的組合，這將使我們能夠在需要提前 9 年時間框架的情況下進行生命週期管理。這些就是我們正在採取的方法，但我們顯然會認真對待您的回饋，並將繼續進行相應的評估。下一個問題，操作員。

Your next question comes from the line of Florent Cespedes from Société Générale.

您的下一個問題來自 Société Générale 的 Florent Cespedes。

A quick one on your mid-term guidance. You have updated this guidance but now starting from a higher base from 2023. I was just wondering if there is anything new versus the last update last year. And if you see, let's say, new drivers that helped you to achieve this midterm guidance.

快速了解您的中期指導。您已經更新了本指南，但現在從 2023 年的更高基數開始。我只是想知道與去年的上次更新相比是否有任何新內容。如果您看到幫助您實現中期指導的新驅動因素。

Yes. Thank you, Florent. I think a few things. So first, in terms of the growth drivers and what we overall saw in the quarter, in quarter 4 and on the full year, you see very dynamic growth for Kesimpta for Kisqali. I think strong growth for Lutathera, Scemblix. And we also saw the return of, as I mentioned, strong demand signals for Pluvicto. All of which gave us confidence in those brands outlook towards our peak sales guidance. In addition, we have now the approval of iptacopan and the iptacopan positive (inaudible) data across PNH C3G and IgAN, which gives us more conviction that this medicine will be a multibillion-dollar medicine as well. So that I think all was on the positive side from in-line brands. And then importantly, with the Scemblix first-line data where we saw, I think, really -- we believe will be potentially practice-changing data. This has an opportunity now as well. There'll be a multibillion-dollar medicine. So taking all of that together, that growth momentum for our in-line brands and strong pipeline performance gave us more conviction in that long-term guide. I would also note, of course, Kisqali now has also filed for medium and high-risk women with early breast cancer. So I think all gives us positive signals and momentum to continue that 5% plus guidance [up to] '28.

是的。謝謝你，弗洛倫特。我想有幾件事。首先，就成長動力以及我們在本季、第四季和全年的整體情況而言，您會看到 Kesimpta 和 Kisqali 的成長非常活躍。我認為 Lutathera 和 Scemblix 的成長強勁。正如我所提到的，我們也看到了對 Pluvicto 的強烈需求訊號的回歸。所有這些都讓我們對這些品牌實現高峰銷售指引的前景充滿信心。此外，我們現在還獲得了 iptacopan 的批准，以及 PNH C3G 和 IgAN 的 iptacopan 陽性（聽不清楚）數據，這讓我們更加確信該藥物也將是一種價值數十億美元的藥物。所以我認為一線品牌的一切都是正面的。然後重要的是，透過我們看到的 Scemblix 一線數據，我認為，我們相信這將是潛在的改變實踐的數據。現在這也有機會。將會有價值數十億美元的藥物。因此，綜合考慮所有這些因素，我們的一線品牌的成長勢頭和強勁的產品線表現讓我們對這一長期指南更有信心。當然，我還要指出的是，Kisqali 現在也為患有早期乳癌的中高風險女性進行了申請。因此，我認為所有這些都給了我們積極的信號和動力，以繼續保持 5% 以上的指導[直到] 28 年。

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格雷厄姆·帕里。

So it's on Pluvicto. So the number in the quarter was a drop off quarter-on-quarter. I think in Q3 that you've actually seen about a 50% increase in patient starts. But also, there was an offsetting factor here of sicker patients not getting the sort of the last 2 doses. So can you just help us with the dynamics of why that increase in patients you saw in Q3 didn't translate into a higher sales number in Q4? And then on sites, I think you'd said 300. So how many are you targeting for 2024 and given your supply unconstrained. is this actually now the rate-limiting step to getting to the multibillion number that you've talked about for the vision indication?

所以它在 Pluvicto 上。因此，本季的數字環比下降。我認為在第三季度，您實際上已經看到患者開始數量增加了約 50%。而且，這裡還有一個抵消因素，就是病情較重的患者沒有接受最後兩劑疫苗的注射。那麼，您能否幫助我們了解為什麼您在第三季度看到的患者數量增加並沒有轉化為第四季度更高的銷售額？然後在網站上，我認為您會說 300 個。那麼考慮到您的供應不受限制，您 2024 年的目標是多少。這實際上是現在達到您所說的視力指示數數十億數字的速率限制步驟嗎？

Yes. Thanks, Graham. So on Pluvicto in quarter 4, we saw a steady rebuild, but I think we do not see yet the full replenishment of the base of patients, given that we still had supply constraints into the August or July-August time line. And so over the course of quarter 4, we saw more patients getting on therapy, which then, of course, gives us the 4 to 6 doses on those patients, which we build that base. I would also say during the holiday period for -- we did see less as we were expecting in the Christmas period and Thanksgiving period, these patients tend not to want to have the therapy given the radiation can lead to -- does lead to a restriction on being around children and other loved ones. So I think those dynamics did play a role. But we did see growth in new patient starts in Q4 versus Q3. But the growth was not, I think, as strong as maybe what the external world predicted. We had tried to guide in quarter 3 to the expectation that we would be to around $1 billion, which is exactly where we are at the $980 million mark. But perhaps we should have been more clear on our outlook and expectation. All of that said, we, of course, can track this on a daily basis, and we see strong growth in demand, strong overall dynamics, and we continue to expect to see robust quarter-on-quarter growth for Pluvicto over the course of this year, getting us back towards that multibillion-dollar outlook that we've guided to in the vision population.

是的。謝謝，格雷厄姆。因此，在第四季度的 Pluvicto 上，我們看到了穩步重建，但我認為我們還沒有看到患者基礎的完全補充，因為我們在 8 月或 7 月至 8 月的時間線中仍然存在供應限制。因此，在第四季度，我們看到更多的患者接受治療，當然，這為我們為這些患者提供了 4 到 6 劑劑量，這是我們建立的基礎。我還要說的是，在假期期間，我們確實看到的情況比我們在聖誕節和感恩節期間預期的要少，這些患者往往不想接受輻射可能導致的治療，這確實會導致限制與孩子和其他親人在一起。所以我認為這些動力確實發揮了作用。但我們確實看到第四季度新患者數量比第三季度有所增長。但我認為，成長並不像外部世界預測的那麼強勁。我們曾試圖將第三季的預期目標定為 10 億美元左右，這正是我們目前 9.8 億美元的目標。但也許我們應該更清楚我們的前景和期望。綜上所述，我們當然可以每天跟踪這一情況，我們看到需求強勁增長，整體動力強勁，我們繼續預計 Pluvicto 在此過程中將出現強勁的季度環比增長今年，讓我們回到我們在有遠見人群中所引導的數十億美元的前景。

And Centers?

還有中心？

And centers -- sorry, Graham. Yes. So our goal is to get to 500 plus centers, and we're expanding now rapidly. I think centers are probably one constraint. And then I think the other in terms of the growth. And so we expect to have (inaudible) at a steady clip over the course of this year. And then we also are encouraging physicians now that supply is unconstrained to treat earlier. So therefore, the average number of patients moves more towards 6 doses per patient which will certainly be our goal over the course of the year. I think both of those dynamics will fuel growth for this brand over the course of 2024.

還有中鋒——對不起，格雷厄姆。是的。所以我們的目標是達到 500 多個中心，而且我們現在正在迅速擴張。我認為中心可能是一個限制因素。然後我認為另一個方面是成長。因此，我們預計今年將維持（聽不清楚）穩定成長。然後，由於供應不受限制，我們也鼓勵醫生儘早治療。因此，平均患者數量朝著每位患者 6 劑的方向發展，這肯定是我們今年的目標。我認為這兩種動力都將推動該品牌在 2024 年的成長。

Your next question comes from the line of [John Plesner] from JPMorgan.

您的下一個問題來自摩根大通的 [John Plesner]。

So you said that the 2024 guidance includes the impact of generics, which we assume is for kind of (inaudible). So what you're thinking behind the actual timings of those generic countries? And Also, you also said that the 2024 guidance could be somewhat prudent. So what are some of the key kind of levers that you could execute on to kind of exceed that guidance?

所以您說 2024 年指南包括仿製藥的影響，我們認為這是針對某種（聽不清楚）的影響。那麼，您在這些通用國家/地區的實際時間安排背後有何想法？此外，您也表示 2024 年的指導可能會有些謹慎。那麼，您可以執行哪些關鍵的槓桿來超越該指導呢？

Yes. Thanks, John. So there are 3 generic entries we would expect over the course of the year, but we're not in a position, I think, to provide specific guidance on when these entries would happen given the, I think, unpredictability, both in terms of our own goals to defend our IP as well as supply for some of these parties. The 3 would be PROMACTA and Tasigna, as you noted, as well as sandostatin LAR where there is no approved generic but no product in the market. We, of course, would provide updates when these would enter over the course of this year. But I think we -- this is our current forecast, and we'll see, of course, how we -- how things evolve. Now in terms of our full year performance, Harry, in terms of the prudent guidance.

是的。謝謝，約翰。因此，我們預計今年會出現 3 個通用條目，但我認為，考慮到不可預測性，我認為我們無法就這些條目何時發生提供具體指導我們自己的目標是保護我們的知識產權以及為其中一些方提供供應。正如您所指出的，這 3 個是 PROMACTA 和 Tasigna，以及 Sandostatin LAR，其中沒有批准的仿製藥，但市場上沒有產品。當然，我們會在今年這些內容進入時提供更新。但我認為，這是我們目前的預測，當然，我們會看到事情如何發展。現在就我們全年的表現而言，哈利，就謹慎的指導而言。

Yes, John, thank you very much. I mean we will not say when we assume (inaudible) financial forecast assumptions. Of course, we do appropriately defend IP when possible. Of course, on Sandostatin LAR, there is no IP anymore. That's more about the ability of the generic producer to produce. It's a very difficult to produce product. On the other hand, we have barely distributed these 3 potential entries for forecast purposes over the quarters. There's a bit of a generic portfolio play, if you will, and now if all of them will come a bit later, then we may have an upside to our guidance. So that's what we meant with that. And of course, overall, we do assume that our key growth drivers continue to perform very well. But it's a bit difficult with these 3 different generics to make assumptions. And so we do them in a prudent way. And there could be changes to this if either one competitor cannot produce or we have some upside on the LOE and patent defense, if you will, on the other 2.

是的，約翰，非常感謝你。我的意思是，我們不會說何時假設（聽不清楚）財務預測假設。當然，我們會盡可能適當地保護智慧財產權。當然，在善寧LAR上，已經沒有IP了。這更多的是關於仿製藥生產商的生產能力。這是一個非常難以生產的產品。另一方面，出於預測目的，我們在這幾個季度中幾乎沒有分發這 3 個潛在條目。如果你願意的話，有一些通用的投資組合遊戲，現在如果所有這些都晚一點出現，那麼我們的指導可能會有好處。這就是我們的意思。當然，總的來說，我們確實認為我們的主要成長動力繼續表現良好。但對這 3 種不同的泛型做出假設有點困難。因此我們會謹慎行事。如果一個競爭對手無法生產，或者我們在 LOE 和專利防禦方面有一些優勢（如果你願意的話），那麼在另外兩個方面，情況可能會改變。

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

您的下一個問題來自沃爾夫研究中心的蒂姆·安德森。

Thank you. On Cosentyx, a question on pricing and market access dynamics in '24, just in the U.S. with multisource biosimilar (inaudible) on the market, now albeit only for 6 to 7 months. Are you seeing any access tightening in '24 such as more step edits given indication overlap? And if not in '24, then do you think it might tighten in 2025? And then also on this topic of just the level of U.S. net price erosion in '24 relative to what it was last year.

謝謝。關於 Cosentyx，一個關於 24 年定價和市場准入動態的問題，就在美國，市場上有多源生物仿製藥（聽不清楚），儘管現在只有 6 到 7 個月。您是否看到 24 年有任何訪問收緊，例如在指示重疊的情況下進行更多步驟編輯？如果不是 24 年，那麼您認為 2025 年可能會收緊嗎？然後還有關於 24 年美國淨價格相對於去年的侵蝕程度的話題。

Yes. Thanks, Tim. In terms of Cosentyx, we actually feel pretty good about overall the access environment for 2024. We've had modest gross-to-net shift overall for the brand, and we have a broader access in some of the major accounts versus what we had in the past. So we haven't seen any, let's call it, increased impact from biosimilar adalimumab. We think this is mostly because we are contracting within the IL-17A class. And given our track record in the class and large position that's enabling us to manage the overall access environment successfully have not seen to my knowledge, any increase in step edits either with respect to Cosentyx access. Now I think looking forward, obviously, always difficult to predict. I think some of the tailwinds we have going for us is the new indications in hidradenitis, which, of course, at least for now, we're only one of few medicines that have that indication, which gives us strength in terms of formulary negotiations. Hopefully, some of the other indications come through as well. Separate from that as well as with Cosentyx, we've launched in the IV setting as well, and that's also another, I think, important growth driver for this medicine over the coming years. So overall, I think a pretty stable position for Cosentyx, at least for 2024 and of course, as we understand better '25 and beyond, we'll keep everybody updated.

是的。謝謝，蒂姆。就 Cosentyx 而言，我們實際上對 2024 年的整體訪問環境感覺非常好。該品牌的總體毛淨值變化不大，並且與我們現有的相比，我們在一些主要帳戶中擁有更廣泛的訪問權限在過去。因此，我們還沒有看到生物相似藥阿達木單抗帶來任何（姑且稱之為）更大的影響。我們認為這主要是因為我們在 IL-17A 級別內簽訂合約。考慮到我們在班級和重要職位中的記錄，使我們能夠成功管理整個訪問環境，據我所知，在 Cosentyx 訪問方面，步驟編輯沒有任何增加。現在我認為展望未來，顯然總是很難預測。我認為我們面臨的一些有利因素是汗腺炎的新適應症，當然，至少目前，我們只是少數具有該適應症的藥物之一，這使我們在處方談判方面具有優勢。希望其他一些跡像也能出現。除此之外，我們還推出了靜脈注射藥物以及 Cosentyx，我認為這也是該藥物未來幾年的另一個重要成長動力。因此，總的來說，我認為 Cosentyx 的地位相當穩定，至少在 2024 年是這樣，當然，隨著我們對 25 年及以後的了解更好，我們將向大家通報最新情況。

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

你的下一個問題來自西蒙貝克（Simon Baker），雷德本（Redburn）。

And it's another one on Cosentyx. I wonder if you could give us your thoughts on the expectation of the uptake for Cosentyx in HS. I've had some clients suggesting it's slower than expected given the quality of the profile and the (inaudible) Competition. How do you see the potential and the uptake there over the course of the next year or so?

這是關於 Cosentyx 的另一項研究。我想知道您是否可以告訴我們您對 HS 中使用 Cosentyx 的預期的想法。我有一些客戶建議，考慮到配置文件的品質和（聽不清楚）競爭，它比預期的要慢。您如何看待未來一年左右的潛力和吸收率？

Yes. Thanks, Simon. I think it's early days. So I think I don't want to, I think, get too far ahead. But so far, we've heard positive feedback overall from clinicians. I mean, Cosentyx has an outstanding long-term safety profile, I think that's been well established now over many, many years, doesn't have some of the safety topics that some of our competitors may have. And so I think that allows us to have a very strong comfort level with dermatologists for treating these patients. And as well, overall, the efficacy, I think, is solid and with the opportunity to give these patients a safe, efficacious option. And as you know, the big challenge in HS is really getting patients to come in to be treated given that it's been so long since there have been new medicines that have been launched since the TNFs were indicated for this condition. So I think solid early start, and we'll certainly see how the quarters unfold, but I think the safety profile and the overall comfort level in dermatologists gives us a very good position for this launch.

是的。謝謝，西蒙。我認為現在還為時過早。所以我想我不想走太遠。但到目前為止，我們從臨床醫生那裡聽到了整體的正面回饋。我的意思是，Cosentyx 具有出色的長期安全性，我認為這一點已經在很多年裡得到了很好的確立，沒有我們的一些競爭對手可能存在的一些安全主題。因此，我認為這使我們能夠對皮膚科醫生治療這些患者感到非常放心。總的來說，我認為療效是可靠的，並且有機會為這些患者提供安全、有效的選擇。如你所知，HS 面臨的巨大挑戰實際上是讓患者前來接受治療，因為自從 TNF 被用於治療這種疾病以來，已經很長時間沒有推出新藥了。因此，我認為早期的起步很紮實，我們肯定會看到各個季度的進展情況，但我認為皮膚科醫生的安全狀況和整體舒適度為我們的這次發布提供了非常好的位置。

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 couple of questions for me, please. Firstly (inaudible) When do you expect that drug to become ineligible for price negotiation under IRA? And given we're moving towards heading up an expiry 2031, can you talk to the life cycle management options available to you here when I look at the Novartis pipeline few breast lands or specific assets, but perhaps [important] feedback you could give there any areas of interest would be greatly received. And then business development. Clearly, you've been somewhat busy over the last 12 months. What's your appetite for deals moving into 2024, size, therapeutic category is RLT still an area of focus for M&A business development. Many banks.

請問我幾個問題。首先（聽不清楚）您預計該藥物何時將不再符合 IRA 下的價格協商資格？考慮到我們正朝著2031 年到期的方向邁進，當我查看諾華的管道時，您能談談可用的生命週期管理選項嗎？一些胸地或特定資產，但也許您可以在那裡提供[重要]反饋任何感興趣的領域都會受到熱烈歡迎。然後是業務發展。顯然，過去 12 個月您有些忙碌。您對進入 2024 年的交易有何興趣、規模、治療類別仍然是 RLT 併購業務發展的重點領域。很多銀行。

Thanks, Kerry. So first on (inaudible) as you know, it's not a precise science to predict IRA for these patients. I'd also note in the early breast cancer population, these patients are younger and tend not to be in the Medicare population. So I'd say we really see this being a topic for Kisqali towards the end of the decade, but importantly, would only affect the portion of our sales that are in the Medicare population. And we'll, of course, as we learn more and understand better how the program will unfold, we'll keep you all updated. But we think we have a very good runway now for this medicine for the coming years, both in metastatic and assuming approval in the early breast cancer space.

謝謝，凱瑞。首先（聽不清楚），如您所知，預測這些患者的 IRA 並不是一門精確的科學。我還想指出，在早期乳癌族群中，這些患者比較年輕，而且往往不屬於醫療保險族群。所以我想說，我們確實認為這是 Kisqali 在本世紀末的一個主題，但重要的是，它只會影響我們在醫療保險人群中的銷售部分。當然，隨著我們了解更多並更好地了解該計劃將如何展開，我們會及時向您通報最新情況。但我們認為，無論是在轉移性乳癌領域，還是在早期乳癌領域，我們認為這種藥物在未來幾年都有一個非常好的跑道。

In terms of life cycle management in breast cancer, of course, the one opportunity is other CDK targets, which we are pursuing in-house, and that's something that we are looking at within our research labs as well as potential for combinations, and that's another topic for us as well. We also continue to advance early stage programs with RLT in breast cancer as well. Not specific life cycle management of Kisqali would give us the opportunity to bring forward radioligand therapies in the breast cancer space and that's an area of high focus for us at the moment. So I think a combination of novel targets in small molecules as well as radioligand therapies in the breast cancer -- overall in the breast cancer space. So in terms of business development, as (inaudible) in the slide, our strategy is very much to focus on our 4 core therapeutic areas and our 3 key technology platforms. So those technology platforms are cell therapy/immune reset, cell and gene therapies immune reset, RLT and RNA therapeutics. And I think that's well known. And in terms of size of deal, no change to our overall approach of smaller than $5 billion bolt-on acquisitions, but the vast majority of those deals being sub-$1 billion deals and no change to our approach there from what we've previously stated. So moving next.

當然，就乳癌的生命週期管理而言，一個機會是我們內部正在追求的其他 CDK 目標，這是我們在研究實驗室中研究的內容以及組合的潛力，這就是我們還有另一個主題。我們也繼續推進乳癌 RLT 的早期計畫。 Kisqali 的非特定生命週期管理將使我們有機會在乳癌領域提出放射性配體療法，這是我們目前高度關注的領域。因此，我認為小分子的新標靶以及乳癌的放射性配體療法的結合——總體而言是在乳癌領域。因此，就業務發展而言，正如幻燈片中的（聽不清楚），我們的策略非常注重我們的 4 個核心治療領域和 3 個關鍵技術平台。這些技術平台包括細胞療法/免疫重置、細胞和基因療法免疫重置、RLT 和 RNA 療法。我認為這是眾所周知的。就交易規模而言，我們對小於 50 億美元的補強收購的總體方法沒有改變，但這些交易中的絕大多數是 10 億美元以下的交易，我們的方法與之前相比沒有改變指出。那麼下一步。

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

您的下一個問題來自古根漢證券公司的 Seamus Fernandez。

So just wanted to ask one particular question in terms of the sort of business development strategy. I know, Vas, you've already talked about this, but I wanted to get a little bit more clarity on specifics around the sort of threshold that you've talked about publicly. Is that sort of $5 billion and below threshold really still kind of the target range? Or given the success that you are seeing in some of the other areas of development. Is there the opportunity to potentially go larger in terms of the potential transactions? Just wanted to get a better sense of if you feel there's more flexibility given the Phase III -- solid Phase III hit rate that you've had or if you're kind of sticking to your guns or to your knitting in the $5 billion in south range?

所以只是想問一個關於業務發展策略的特定問題。我知道，Vas，您已經討論過這一點，但我想更清楚地了解您公開討論的閾值的具體細節。 50 億美元及以下的門檻真的仍然是目標範圍嗎？或考慮到您在其他一些發展領域所看到的成功。就潛在交易而言，是否有機會擴大規模？只是想更好地了解您是否認為第三階段有更大的靈活性——您已經擁有的穩定的第三階段命中率，或者您是否在 50 億美元中堅持自己的立場或編織方式南嶺？

Yes. Thanks, Seamus. So really nothing, I think, to add beyond what I've already stated. I mean we of course, look at the full range, as you would expect a company of our size, a full range of potential opportunities within business development. But what we consistently see is the opportunities we have, where there is the most significant opportunity for value creation as well as a differentiated view versus the market is on the lower end of the range of deal values. I think that's why when you look at the 15-plus deals that we did last year, vast majority are under $1 billion or even under $500 million, we did Chinook at $3.1 billion. And I think that's where we see the best opportunities for us as a company. I will never exclude that we would do anything if it makes sense for our shareholders and makes sense for the long-term profile of Novartis. But our focus is very much on that bolt-on sub-5, sub-$1 billion range programs, and that's where I think will be.

是的。謝謝，西莫。因此，我認為，除了我已經說過的內容之外，沒有什麼可補充的了。我的意思是，我們當然會關注全方位的業務發展中的潛在機會，正如您對我們規模的公司所期望的那樣。但我們始終看到的是我們擁有的機會，其中存在著最重要的價值創造機會，以及與市場處於交易價值範圍下端的差異化觀點。我認為這就是為什麼當你看看我們去年完成的 15 多筆交易時，絕大多數交易金額都在 10 億美元以下，甚至低於 5 億美元，而我們以 31 億美元的價格完成了 Chinook。我認為這對我們公司來說是最好的機會。我永遠不會排除我們會做任何事情，如果這對我們的股東有意義並且對諾華的長期形像有意義的話。但我們的重點主要集中在 5 億美元以下、 10 億美元以下的補充項目上，我認為這就是重點。

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

你的下一個問題來自巴克萊銀行的艾米莉·菲爾德。

Just a question on -- but -- how far along are you in the recruitment of the MS trials, just given we've seen another partial clinical hold in the space? And then if you could just remind us how your molecule is differentiated given the -- we did see that Phase III failure after you're on (inaudible)

只是一個問題，但是，考慮到我們已經看到該領域的另一個部分臨床進展，你們在招募多發性硬化症試驗方面進展到了什麼程度？然後，如果你能提醒我們你的分子是如何區分的——我們確實看到了你進入後的第三階段失敗（聽不清楚）

Yes. Thanks, Emily. So on [REMS Bruce,] let me start with why we think our molecule is differentiated. When you look at the structures and if you go back to some of our slides in R&D Day, you'll see that our molecule as a different overall chemo type structure than some of the other peers, we believe that the liver signals that have been seen thus far in this group of medicines has to do with off-target toxicities related to the structure of the molecule. So we have a highly potent BTK inhibitor, a covalent BTK inhibitor that we think is unique and it's at least so far in the clinical and preclinical work profile in terms of having any of those off-target toxicities. So we, of course, already have read out 2 positive Phase III studies in CSU and plan to file with the 52-week data in the second half of this year. We continue to pursue as well remibrutinib in other immunology indications where we think there is an opportunity given it's a safe profile. And importantly, at that dose range, 25 milligrams BID, we saw no liver signals in those dermatology studies. In terms of the MS trials, we continue to recruit on track. However, we don't expect a filing before 2026, if I'm not mistaken. And we did have a futility analysis looking at futility for noninferiority to our comparator, and we pass that futility analysis. So the program will continue. So we don't see any safety signals. We've passed a futility analysis, which we put in place given some of the data that some of our peers have read out, and we'll continue then to progress the study in multiple sclerosis as well. We do believe remibrutinib has the opportunity to be a significant medicine across a range of indications, particularly as the safety profile continues to hold up because of the structure of the medicine.

是的。謝謝，艾米麗。因此，在 [REMS Bruce] 中，讓我從為什麼我們認為我們的分子是與眾不同的開始。當您查看結構時，如果您回到研發日的一些幻燈片，您會發現我們的分子與其他一些同行相比具有不同的整體化學類型結構，我們相信肝臟信號已被迄今為止，在這組藥物中發現與分子結構相關的脫靶毒性有關。因此，我們有一種高效的 BTK 抑制劑，一種我們認為是獨特的共價 BTK 抑制劑，至少到目前為止在臨床和臨床前工作中它具有任何脫靶毒性。當然，我們已經在科羅拉多州立大學宣讀了兩項積極的 III 期研究，並計劃在今年下半年提交 52 週的數據。我們繼續在其他免疫學適應症中尋求瑞布替尼的治療，我們認為鑑於其安全性，在這些適應症中存在機會。重要的是，在 25 毫克 BID 的劑量範圍內，我們在那些皮膚學研究中沒有看到肝臟訊號。在 MS 試驗方面，我們繼續按計劃進行招募。不過，如果我沒記錯的話，我們預計不會在 2026 年之前提交申請。我們確實進行了無效性分析，著眼於與我們的比較器相比的非劣效性，並且我們通過了無效性分析。因此該計劃將繼續進行。所以我們沒有看到任何安全訊號。我們已經通過了一項無效分析，我們根據一些同行讀出的一些數據進行了分析，然後我們也將繼續推進多發性硬化症的研究。我們確實相信瑞米布替尼有機會成為涵蓋一系列適應症的重要藥物，特別是由於該藥物的結構，其安全性繼續保持不變。

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。

Just curious, I would come back to (inaudible) You sort of had some more cautious commentary perhaps than you might expect it for a new launch I wonder if you could just talk a little bit about does this, as you say, relate very specifically to the PNH market and perhaps why you have more confidence that you potentially can't get into some of those currently untreated patients sooner? Or does it reflect the REMS the initial program and perhaps impediments you're seeing getting this in front of doctors and through the process than perhaps you envisaged? And I guess, how does that and the profile of the drug, if at all, read into the potential rollout for the larger IgAN indication potentially in the future.

只是好奇，我會回來（聽不清楚）你的評論可能比你對新發布的預期更加謹慎，我想知道你是否可以談談這是否如你所說，非常具體也許您對PNH 市場更有信心，認為您可能無法更早接觸一些目前未經治療的患者？或者它是否反映了 REMS 的初始計劃，以及您在醫生面前和整個過程中看到的可能比您預想的障礙？我想，如果有的話，這和藥物的概況如何解讀未來可能推出的更大的 IgAN 適應症。

Yes. Thanks, Peter. So first on P&A, it very much -- the uptake very much has to do with the REMS as well as some of the other elements that need to be placed. So particularly vaccinations. And so this takes time to put in place for this medicine as well as our organization, getting the infrastructure fully up and running. We estimate 7,000 to 8,000 patients with PNH in the United States, roughly 3,000 to 4,000 of them being treated as today. And so in such an ultra-rare patient population as well, you have a relatively high dispersion of physicians who are treating 1 or 2 patients. It also takes time to reach all of these physicians. It doesn't change our long-term belief that this is -- can become the medicine of choice for these patients given it's a twice-a-day safe oral medicine with high efficacy and I think a reasonable safety profile overall. And that will just take time as we get physicians up to speed, either patients in a position where they need to switch because they're uncontrolled, over time, even controlled patients, we would argue would want to be switched and then new starts as well. And then we do make efforts already to try to reach that half of the -- estimated half of the patient population, which is currently untreated. So we just want to set reasonable expectations for the first year that we hope to ramp up thereafter. We do think that given our positioning in C3G and IgAN. C3G, already also being an ultra-rare disease; IgAN, we target refractory patients, again, given that we're targeting a very select patient population, we think we can absolutely manage the patient start process for those patients and then ensure a very strong uptake for the medicine. And then if you look at the future indications for largely also in the ultra-rare space, which will then -- I think as we build that capability, we should be able to get patients on therapy sustainably over time.

是的。謝謝，彼得。首先，關於 P&A，它的吸收很大程度上與 REMS 以及需要放置的其他一些元素有關。特別是疫苗接種。因此，這種藥物以及我們的組織都需要時間來落實到位，使基礎設施全面啟動並運作。我們估計美國有 7,000 至 8,000 名 PNH 患者，其中約 3,000 至 4,000 名患者目前正在接受治療。因此，在如此罕見的患者群體中，治療 1 或 2 名患者的醫生也相對分散。聯繫所有這些醫生也需要時間。它不會改變我們的長期信念，即它可以成為這些患者的首選藥物，因為它是一種每天兩次的安全口服藥物，具有高效能，而且我認為整體安全性合理。這需要時間，因為我們讓醫生跟上進度，要么患者處於需要轉換的位置，因為他們不受控制，隨著時間的推移，即使是受控制的患者，我們認為也會想要轉換，然後新的開始出色地。然後，我們確實已經在努力爭取涵蓋目前尚未接受治療的估計一半的患者群體。因此，我們只想為第一年設定合理的預期，並希望此後能有所提升。考慮到我們在 C3G 和 IgAN 中的定位，我們確實這麼認為。 C3G，也已經是一種極為罕見的疾病； IgAN，我們的目標是難治性患者，考慮到我們的目標是非常精選的患者群體，我們認為我們絕對可以管理這些患者的患者啟動過程，然後確保藥物的強烈吸收。然後，如果你看看未來的適應症，主要也是在極其罕見的領域，那麼我認為，隨著我們建立這種能力，我們應該能夠隨著時間的推移讓患者持續接受治療。

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

您的下一個問題來自法國巴黎銀行的理查德帕克斯。

It's just following up on business development strategy. I mean it's been quite clear the last 18 months, you're now very confident about growth through upcoming LOEs for the business overall, but you still will have to absorb LOEs in specific therapeutic categories and also be thinking about Entresto. So when you look at your cardiovascular franchise, given that [LOEs] maybe been a bit slower and a (inaudible) clinical risk, are you confident you've got enough coming through maintaining a healthy front that had not had any kind of negative leverage post that? Or is that an area where you would look to maybe be more active in terms of business development to bring in later-stage products?

它只是跟進業務發展策略。我的意思是，過去 18 個月的情況已經很清楚了，您現在對透過即將到來的整體業務 LOE 實現成長非常有信心，但您仍然必須吸收特定治療類別中的 LOE，並考慮 Entresto。因此，當您查看您的心血管專營權時，考慮到[LOE] 可能會慢一些並且存在（聽不見的）臨床風險，您是否有信心通過保持健康的前線（沒有任何負面影響）來獲得足夠的收益發布那個？或者您希望在該領域更加積極地進行業務開發以引入後期產品？

Yes. Thanks, Richard. We feel very confident with what we have in-house in cardiovascular disease. When you look at it, we have Leqvio in secondary prevention and then moving to primary prevention as well. we have pelacarsen of the Lp(a) program. We have a program called [XX B,] which we are currently moving forward in mid-stage studies in hypertension and heart failure as well as an oral version of XXP as well NPR1 agonist that we're also bringing forward. And as I've noted, we have an extensive in-house siRNA effort targeting a range of lipid lowering and cardiovascular targets as well as external collaborations that we've also now brought on board, which we think allows us to cover most of the key targets, which would be of interest for siRNAs. And our goal is one, to move to new targets; two, to move to combinations; and three, also to get to annual dosing, which we think is the right strategy in cardiovascular disease in the long run. Of course, other companies are pursuing orals and fully understand that. But we believe that in this space, given the compliance challenge over the long run that's been demonstrated over decades, having infrequently administered siRNAs on validated targets is the right strategy. So given all of that and the efforts that we have ongoing, we feel very comfortable with our internal cardiovascular portfolio and pipeline. Next question, operator?

是的。謝謝，理查。我們對心血管疾病領域的內部技術充滿信心。當你看到它時，我們將 Leqvio 應用於二級預防，然後也轉向一級預防。我們有 Lp(a) 計劃的 pelacarsen。我們有一個名為 [XX B] 的項目，目前正在高血壓和心臟衰竭的中期研究中取得進展，我們也正在推出 XXP 的口服版本以及 NPR1 激動劑。正如我所指出的，我們有廣泛的內部 siRNA 工作，針對一系列降脂和心血管目標，以及我們現在也引入的外部合作，我們認為這使我們能夠涵蓋大部分siRNA 感興趣的關鍵目標。我們的目標是：邁向新目標；二、轉向組合；第三，也要達到每年給藥劑量，我們認為長期來看，這是治療心血管疾病的正確策略。當然，其他公司也在追求口頭，也充分理解這一點。但我們相信，在這個領域，考慮到幾十年來所證明的長期合規性挑戰，在經過驗證的目標上不頻繁地施用 siRNA 是正確的策略。因此，考慮到所有這些以及我們正在進行的努力，我們對我們的內部心血管產品組合和管道感到非常滿意。下一個問題，接線生？

(Operator Instructions) Your next question comes from the line of Mark Purcell from Morgan Stanley.

（操作員指示）您的下一個問題來自摩根士丹利的馬克·珀塞爾（Mark Purcell）。

On Kesimpta, hopefully you can help us understand the growth dynamics here and leadership means, especially in light of the U.S. acceleration. So when you think about B-cell NBRx share, how does the ex U.S. share compared to the U.S. where we get data from Roche? And then when I look to the [MB] leadership footnote in 7 out of 10 markets, just that data on file. So could you help us understand, I guess, where infusions are more of a barrier to treat mix in some ex U.S. markets versus U.S., where your share stands to the alternative infused therapy in this space? And then just a housekeeping on Kisqali and the [NatLi filing,] did you include no negative patients in that filing?

關於 Kesimpta，希望您能幫助我們了解這裡的成長動態和領導力手段，特別是考慮到美國的加速成長。那麼，當您考慮 B 細胞 NBRx 份額時，與我們從羅氏獲得數據的美國相比，美國以外的份額如何？然後，當我查看 10 個市場中有 7 個市場的 [MB] 領導腳註時，只是存檔的數據。那麼，我想，您能否幫助我們了解，與美國相比，輸液在美國以外的一些市場上是混合治療的更大障礙，您在該領域相對於替代輸液療法的份額在哪裡？然後只是對 Kisqali 和 [NatLi 文件] 進行整理，您在該文件中是否未包含陰性患者？

Yes. Thanks, Mark. So Kisqali, yes, no negative patients were included. On Kesimpta, so first on the ex U.S. dynamics, I think, first, it's important to note outside of the U.S., you don't have the same structure as Part B for providing an infused medicine and many of these healthcare systems as there's a preference to move patients out of the medical centers and medical homes and more having at-home therapies. So in those key markets, we really see a dynamic. I don't know that the specific shares off hand, but we see a dynamic where we are being a favored class of medicines in some of the large ex U.S. markets. We have very strong performance in markets like Germany, very strong performance in markets like Japan. And so I think that's really just a reflection of different dynamics in those markets where there's a preference for neurologists to provide patients a medicine that's easy for at-home use. And we hope, over time, as we now move Kesimpta more broadly across Europe and Asia. We have the opportunity to drive significant growth ex U.S. In the U.S., there is different dynamics. Right now, we estimate that the B-cell class share of NBRx is in the mid-50% range, 55%. And over time, we expect that to continue to grow. Kesimpta's share within the B-cell class is in the high 20s, 27% to 30%, depending on when you look. And we right now are growing with the B-cell class overall. But very much our goal over time is to grow our share of the B-cell class, and that's something we're very much focused on. That will take, I think, time for us to achieve, but that's going to be important if we want to get well beyond the $4 billion guidance we've already given. We think we can get to the $4 billion just by the march of the B-cell class. But if we want to do better, we need to improve our B-cell class share in the U.S., and that's something we're definitely focused on.

是的。謝謝，馬克。所以基斯卡利，是的，沒有包括陰性患者。關於 Kesimpta，首先是關於前美國的動態，我認為，首先，重要的是要注意在美國以外的地區，您沒有與 B 部分相同的結構來提供輸液藥物和許多此類醫療保健系統，因為有一個傾向於將患者移出醫療中心和醫療之家，更多地接受家庭治療。因此，在這些關鍵市場中，我們確實看到了活力。我不知道具體的份額，但我們看到了一種動態，即我們在美國以外的一些大型市場中成為受歡迎的藥品類別。我們在德國等市場的表現非常強勁，在日本等市場的表現也非常強勁。因此，我認為這實際上只是這些市場中不同動態的反映，在這些市場中，神經科醫生更傾向於為患者提供容易在家使用的藥物。我們希望隨著時間的推移，我們現在可以將 Kesimpta 推廣到歐洲和亞洲更廣泛的地區。我們有機會推動美國以外地區的顯著成長。在美國，存在著不同的動態。目前，我們估計 NBRx 的 B 細胞類別份額處於 50% 的中間範圍，即 55%。隨著時間的推移，我們預計這一數字將繼續增長。 Kesimpta 在 B 細胞類別中的份額在 20 多歲之間，為 27% 到 30%，具體取決於您觀察的時間。我們現在正在與 B 細胞類別一起成長。但隨著時間的推移，我們的目標是增加 B 細胞類別的份額，這是我們非常關注的事情。我認為，我們需要時間才能實現這一目標，但如果我們想遠遠超出我們已經給出的 40 億美元的指導，這一點就很重要。我們認為，只要 B 細胞類別的進步，我們就能達到 40 億美元。但如果我們想做得更好，我們需要提高我們在美國的 B 細胞類別份額，這絕對是我們關注的重點。

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。

I'm curious what happens with Entresto IRA price negotiation in 2026 when generics can launch in 2025? It would seem that if there were an Entresto generic, then Entresto would not be eligible for a price negotiation. Is that how you see it? And has that come up in price negotiations so far? If yes, then the best case it would seem for Novartis would be limited generic competition, maybe even an authorized, which could turn out to be a plus for Entresto revenue.

我很好奇當仿製藥可以在 2025 年推出時，2026 年 Entresto IRA 價格談判會發生什麼？看起來，如果有 Entresto 仿製藥，那麼 Entresto 將沒有資格進行價格談判。你是這樣看的嗎？到目前為止，這一點在價格談判中是否已提及？如果是的話，那麼對諾華來說最好的情況似乎是有限的仿製藥競爭，甚至可能是授權競爭，這可能會為 Entresto 收入帶來好處。

Yes. Thanks, Steve. So it is a valid point. And our position would be if there is a generic that's launched that a medicine in our portfolio for the current the guidance of the IRA would not be eligible at that point in time. So that would be our view. But I think, as you know, there's many things that are still unfolding with respect to the IRA negotiation. I obviously can't comment on our our approach to the various generic entrants and our approach on how to manage that. I would say that look, for Entresto, even beyond in the U.S., we guide to this 2025 -- mid-2025 LOE and an IRA if we were to move -- not have a generic enter in 2025, we would be IRA eligible in early 2026. So one way or another, we are going to have Entresto being impacted in this period of time. What is important to note is we guide to 5% plus for '23 to '28 growth even with Entresto coming out in the U.S. and also coming out in Europe, given the time line of our RDP in Europe. So I think we feel confident we can grow well beyond the Entresto LOE or IRA. However, it ultimately happens in that period. Next question, operator?

是的。謝謝，史蒂夫。所以這是一個有效的觀點。我們的立場是，如果有一種仿製藥上市，那麼我們投資組合中當前 IRA 指導下的藥物在那時將不符合資格。這就是我們的觀點。但我認為，正如你所知，關於愛爾蘭共和軍的談判還有很多事情正在展開。顯然，我無法評論我們對各種通用進入者的方法以及我們對如何管理它的方法。我想說的是，對於Entresto，甚至在美國之外，我們將指導到2025 年——2025 年中期的LOE 和IRA（如果我們要搬家）——在2025 年沒有通用的輸入，我們將有資格獲得IRA 2026 年初。因此，無論怎樣，我們將在這段時間內讓 Entresto 受到影響。值得注意的是，考慮到我們在歐洲的 RDP 時間表，即使 Entresto 在美國上市，也在歐洲上市，我們仍預計 23 年至 28 年的成長將達到 5% 以上。因此，我認為我們有信心超越 Entresto LOE 或 IRA 的發展。然而，它最終發生在那個時期。下一個問題，接線生？

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

您的下一個問題來自瑞銀集團 (UBS) 的馬修‧韋斯頓 (Matthew Weston)。

It's a follow-up on Pluvicto. Vas, I think it's JPMorgan and at the R&D Day, you highlighted PSMA 4 filing in 2024. Now it's the second half of 2024. So can you give us an update? Has anything changed? And also, can you just give us an update on your discussions with regulators? I know there's been a lot of discussion about the modeled control arm, given the significant crossover, can you give investors comfort that you're still confident that it will be acceptable to FDA and regulators around the world?

這是 Pluvicto 的後續作品。 Vas，我想是摩根大通，在研發日，您強調了 2024 年的 PSMA 4 備案。現在是 2024 年下半年。那麼您能為我們介紹一下最新情況嗎？有什麼改變嗎？另外，您能否向我們介紹一下您與監管機構討論的最新情況？我知道關於建模控制臂已經有很多討論，考慮到顯著的交叉，您能否讓投資者放心，您仍然相信它會被 FDA 和世界各地的監管機構接受？

Yes. Thanks, Matthew. So we don't have any updates. The trial continues to accrue events. I mean based on our our current estimates, we think the second half 2024 filing is the right timeline to provide at this point in time. But of course, this will evolve as the events accrue. In terms of our confidence, nothing has changed. When you look at the overall data set that you saw last year, you saw very impressive gains in our PFS. You saw impressive gains in ORR. You saw a high quality of life improvement, a relatively clean safety profile even versus ARPI comparator arm. So I think a positive safety profile overall. So we think we have a very compelling case. We think it's really a matter of getting to the higher resolution both in terms of the adjusted analysis where we're already below a hazard ratio of as well as a tighter radius around the all-comers analysis as well for the OS. And so this will be, of course, a topic of discussion with the FDA, but we think we can make a very clear and compelling case that this medicine should be offered to patients in the (inaudible) setting, and then we also are continuing, as I mentioned, to move forward rapidly on PSMA addition as well as Pluvicto in the oligometastatic setting, so we can cover all of our bases. I do think, overall, as an industry, we'll learn more with some of the upcoming ADCOMs on -- from other competitor medicines on how the FDA is thinking about OS, crossover and how to manage this. And I'm hopeful that overall patient benefit is what ultimately rules out over some of the statistical -- pure statistical considerations given that we are encouraged to utilize crossover in our studies to be patient-friendly in an appropriate way. I think it's very important we start to be looking at the adjusted analysis, otherwise, this puts the overall the industry in a very challenging position. Next question, operator?

是的。謝謝，馬修。所以我們沒有任何更新。審判繼續發生事件。我的意思是，根據我們目前的估計，我們認為 2024 年下半年提交文件是此時提供的正確時間表。但當然，這會隨著事件的發生而演變。就我們的信心而言，沒有任何改變。當您查看去年看到的整體資料集時，您會發現我們的 PFS 取得了非常令人印象深刻的進步。您看到了 ORR 的顯著提升。您看到了生活品質的提高，甚至與 ARPI 比較臂相比，安全狀況也相對乾淨。所以我認為整體安全狀況是正面的。所以我們認為我們有一個非常有說服力的案例。我們認為這實際上是一個獲得更高解析度的問題，無論是在調整後的分析方面，我們已經低於風險比，還是在所有參與者分析周圍以及操作系統上都有更嚴格的半徑。因此，當然，這將是與FDA 討論的一個話題，但我們認為我們可以提出一個非常明確和令人信服的案例，即這種藥物應該在（聽不清）環境中提供給患者，然後我們也將繼續正如我所提到的，在寡轉移環境中快速推進 PSMA 添加以及 Pluvicto，這樣我們就可以覆蓋所有基礎。我確實認為，總體而言，作為一個行業，我們將透過一些即將推出的 ADCOM 從其他競爭對手的藥品中了解 FDA 如何考慮作業系統、交叉以及如何管理這一點。我希望患者的整體利益最終會排除一些統計因素——純粹的統計考慮因素，因為我們被鼓勵在研究中利用交叉以適當的方式對患者友好。我認為我們開始考慮調整後的分析非常重要，否則，這將使整個產業處於非常具有挑戰性的境地。下一個問題，接線生？

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格雷厄姆·帕里。

Just wanted to dig into some of the moving parts for the guide on generics, you sort of made some sort of high-level comments there. But in terms of the ability to manufacture, I assume that Sandostatin LAR, I think have gotten approval December. But is that restriction a legal one? So is there any litigation around manufacturing, even if there isn't around the approval or is that a tech ops consideration there? And then on Promacta, I believe there's no litigation outstanding, you have a salt pattern in 2026. So what are the moving parts for timing of the launch there? And is 2025 or '26 launch on Promacta even also still a possibility?

只是想深入了解仿製藥指南的一些動態部分，您在那裡發表了一些高級評論。但就生產能力而言，我認為善寧 LAR 已於 12 月獲得批准。但這限制合法嗎？那麼，即使沒有批准，是否存在圍繞製造的任何訴訟，或者這是技術運營的考慮？然後在 Promacta 上，我相信沒有未決的訴訟，2026 年有一個鹽模式。那麼在那裡發佈時間的變化因素是什麼？ 2025 年或 26 年在 Promacta 上發布還有可能嗎？

Yes. Thanks, Graham. On Sandostatin, we -- there is no litigation ongoing. I think -- and I can't comment on other companies' manufacturing capabilities. I think what we did observe in Europe with the launch of generics is there was limited supply available for those launches given the complexity of the manufacturing. And we believe that that's a complexity as well that would still be the case in the U.S. This is a very difficult medicine to consistently make and characterized and release. But obviously, that's for the approved generics to ultimately determined. So we'll be monitoring to see how and when that product comes to market and in what volumes. And in the meantime as well, I mean, we very much are focused on our Lutathera frontline data, where we, I think, presented really compelling data to make Lutathera, the medicine -- frontline medicine of choice. It's already on label. We're already promoting that to physicians, making sure physicians understand the data set that we've now generated with the NETTER-2, that gives us an opportunity as well to maintain our neuroendocrine tumor business. With respect to Promacta, not much more I can add. We, of course, continue to defend our IP, and we'll do so and try to maintain the medicines protection for as long as possible. But at this point in time, I can't provide any further details or guidance on Promacta. For forecasting purposes, we're saying a generic entry in 2024. But as always, we defend our IP to the fullest extent possible. Moving to the last question, operator?

是的。謝謝，格雷厄姆。關於善寧，我們沒有正在進行的訴訟。我認為——而且我無法評論其他公司的製造能力。我認為我們在歐洲推出仿製藥時確實觀察到，鑑於製造的複雜性，這些產品的供應有限。我們相信，這也是一種複雜性，在美國仍然會出現這種情況。這是一種非常難以持續製造、表徵和釋放的藥物。但顯然，這要由核准的仿製藥最終決定。因此，我們將密切關注該產品如何、何時上市以及上市量。同時，我的意思是，我們非常關注 Lutathera 的一線數據，我認為我們提供了真正令人信服的數據，使 Lutathera 這種藥物成為首選的一線藥物。它已經在標籤上了。我們已經向醫生推廣這一點，確保醫生了解我們現在使用 NETTER-2 產生的數據集，這也為我們提供了維持神經內分泌腫瘤業務的機會。關於 Promacta，我無法補充太多。當然，我們將繼續捍衛我們的智慧財產權，我們將這樣做並盡力盡可能長時間地維持藥品保護。但目前，我無法提供有關 Promacta 的任何進一步細節或指導。出於預測目的，我們所說的一般進入時間是 2024 年。但與往常一樣，我們會盡最大努力保護我們的智慧財產權。轉到最後一個問題，操作員？

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

您今天的最後一個問題來自沃爾夫研究中心的蒂姆·安德森。

Thank you so much. Obesity, I think you've been asked this before, but quite possibly the biggest therapeutic category. You guys have a big presence in cardiometabolic, how high of a priority is it to enter the space? There are acquirable assets in clinical development. They fall into that sub-$5 billion range. Why not move on one of them, can't late entrant products still capture revenues or (inaudible) just too far ahead to justify the cost of a competitive development program?

太感謝了。肥胖，我想您以前曾被問過這個問題，但很可能是最大的治療類別。你們在心臟代謝領域佔有重要地位，進入這個領域的優先順序有多高？臨床開發中有可取得的資產。它們屬於 50 億美元以下的範圍。為什麼不繼續其中一個，後來進入的產品不能仍然獲得收入或（聽不清楚）太領先以至於無法證明競爭性開發計劃的成本是合理的？

Yes. Thanks, Tim. So look, when we think about the obesity market, we very much look at it in the lens of our presence in cardiovascular disease and wanting to ensure we have a presence that enables future cardiovascular drugs we have in our pipeline to either be combinable or available to patients with the full range of cardiovascular disease. So it's certainly something we're evaluating and looking at. Our current view is that given the number of companies already pursuing injectable and oral GLP, GIP top assets that we should be focused on differentiated assets that have novel targets or novel approaches, novel profiles, which is what we look at in research. But of course, we evaluate all the opportunities that are currently out there, given the size of this market and the importance for cardiovascular health. So obviously, if we find something of interest, we'll pursue it. But at the moment, I can't really say anything specific about anything we're looking at.

是的。謝謝，蒂姆。所以，當我們考慮肥胖市場時，我們非常從我們在心血管疾病領域的存在角度來看待它，並希望確保我們的存在能夠使我們管道中的未來心血管藥物能夠組合或可用患有各種心血管疾病的患者。所以這肯定是我們正在評估和研究的事情。我們目前的觀點是，考慮到已經有許多公司在追求注射劑和口服GLP、GIP 頂級資產，我們應該專注於具有新目標或新方法、新特徵的差異化資產，這正是我們在研究中關注的內容。當然，考慮到這個市場的規模和對心血管健康的重要性，我們會評估目前存在的所有機會。顯然，如果我們發現感興趣的東西，我們就會追求它。但目前，我無法具體說明我們正在研究的任何內容。

Perfect. Thanks, everyone, for joining. We look forward to keeping you updated over the course of the year and wish everyone (inaudible) 2024.

完美的。謝謝大家的加入。我們期待在這一年中為您提供最新信息，並祝大家（聽不清楚）2024 年一切順利。

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。