AstraZeneca PLC (AZN) 2023 Q4 法說會逐字稿

Well, a warm welcome, everybody, to AstraZeneca's Fourth quarter and full year '23 results presentation conference call and webcast for investors and analysts. I'm Andy Barnett, Head of Investor Relations. And before I hand over to Pascal and members of the executive team, I'd like to cover some important housekeeping points.

熱烈歡迎大家參加阿斯特捷利康 23 年第四季和全年業績發表會以及為投資者和分析師舉辦的網路直播。我是投資者關係主管安迪·巴尼特。在我向帕斯卡和執行團隊成員移交之前，我想先介紹一些重要的內務要點。

Firstly, as I'm probably sure you realize all the materials are already on our website for your review. Here is our forward-looking statement, which I'd encourage you to take the time to read. We'll be making comments on our performance using constant exchange rates, or CER, core financial numbers and other non-GAAP measures and non-GAAP to GAAP reconciliation is contained within the results announcement that you all have seen. All numbers quoted are in millions of U.S. dollars unless otherwise stated.

首先，我可能確信您已經意識到所有資料都已在我們的網站上供您審查。這是我們的前瞻性聲明，我鼓勵您花時間閱讀。我們將使用固定匯率（CER）、核心財務數據和其他非 GAAP 指標對我們的業績做出評論，非 GAAP 與 GAAP 的調整包含在你們都看到的結果公告中。除非另有說明，所有引用的數字均以百萬美元為單位。

This slide shows the agenda for today's call. Following our prepared remarks, we'll open the line for questions. Of course, if you want to raise a -- ask a question in the room, you raise your hands, there'll be roving mics. For those online, please use the zoom function to raise your hand. As usual, we'll try and get through as many questions as we can through the course of the call. But if you limit the number of questions you ask it once, it will give others a fair chance to participate. And with that, Pascal, I'm going to hand over to you.

這張投影片顯示了今天電話會議的議程。在我們準備好的發言之後，我們將開通提問熱線。當然，如果你想在房間裡提出問題，你舉手，就會有流動麥克風。線上的請使用縮放功能舉手。像往常一樣，我們將在通話過程中嘗試解決盡可能多的問題。但如果你限制一次提出的問題數量，就會給其他人一個公平的參與機會。帕斯卡，接下來我就把任務交給你了。

Thank you, Andy. Good morning, everybody, and welcome to this London Stock Exchange, where we are celebrating our 25th anniversary as a company merging us from Sweden and Zeneca from the U.K. quite a number of years ago. But I want to start my talk with this slide. And this slide is important because I want to recognize or celebrate the fact that not only it's our 25th anniversary, but importantly, we actually did achieve the goal we set ourselves 10 years ago to reach $45 billion sales in 2023. .

謝謝你，安迪。大家早安，歡迎來到倫敦證券交易所，我們正在慶祝多年前瑞典公司和英國捷利康公司合併後的公司成立 25 週年。但我想從這張投影片開始我的演講。這張投影片很重要，因為我想承認或慶祝這樣一個事實：這不僅是我們的25 週年紀念日，而且重要的是，我們實際上實現了10 年前設定的目標，即2023 年銷售額達到450 億美元。

And in fact, I could argue, we overachieved it because at the current exchange rates, our $20 billion -- $45 billion goal probably is closer to $40 billion. And I don't want to say just to kind of pat ourselves in the back, even though, I'd like to do this and celebrate our team's effort. But I want to mention it because we always did this with our eyes on the long-term growth. And we are embarking on another 10-year cycle. And we have announced an R&D Day because we want to refresh our strategy and show you what we are planning to do over the next 10 years. But we got this $45 billion through ups and downs, and I have to say often a lot of skepticism, but always with our eye on the long-term growth rate. And that's what we're going to do.

事實上，我可以說，我們超額實現了這個目標，因為以目前的匯率，我們 200 億至 450 億美元的目標可能更接近 400 億美元。我並不是想說只是為了拍拍自己的背，儘管如此，我還是想這樣做並慶祝我們團隊的努力。但我想提一下，因為我們這樣做總是著眼於長期成長。我們正在開始另一個十年周期。我們宣佈設立研發日，因為我們想更新我們的策略並向您展示我們在未來 10 年計劃做什麼。但我們經歷了風風雨雨才獲得了這 450 億美元，我不得不說經常持很多懷疑態度，但我們始終著眼於長期增長率。這就是我們要做的。

We believe we can grow, and we believe over the next 10 years, we will deliver superior growth. And that's, of course, going to drive our profitability as a result of it. But our growth and sustainable strong growth is really what we are after.

我們相信我們能夠成長，而且我們相信在未來 10 年裡，我們將實現卓越的成長。當然，這將提高我們的獲利能力。但我們的成長和可持續的強勁成長才是我們真正追求的。

And we've done this whole following the science. And again, we are embarking on a new cycle, and we are investing in new science that will shape the future of medicine and shape the future of this company, and we can talk more about this.

我們是按照科學來完成這一切的。再說一次，我們正在開始一個新的週期，我們正在投資新的科學，這將塑造醫學的未來，塑造這家公司的未來，我們可以更多地談論這一點。

We have achieved this whole disciplined investment, even though we often have extensive debate inside the company and I know it's challenging everybody to be even more disciplined in terms of our investment. But we've constantly focused our investment on where we can deliver the most growth and also continuously focusing on oncology, cardiovascular disease, prosperity disease more recently increasing our high -- increasing our investment and keeping our eye on immune diseases and finally, rare diseases.

儘管我們經常在公司內部進行廣泛的辯論，但我們已經實現了整個嚴格的投資，我知道這對每個人來說都是一個挑戰，要求我們在投資方面更加嚴格。但我們持續將投資集中在能夠實現最大成長的領域，並持續關注腫瘤學、心血管疾病、繁榮疾病，最近增加了我們的投資，並密切關注免疫疾病，最後是罕見疾病。

And the company we have today and the team we have today is very different from what it was 10 years ago. And it's really rewarding to see the progress we've made and the strengths we have developed in our portfolio, but also in the strength of the talent in the company. The way we operate in oncology today, and the same in the other TAs is very, very different. And it gives me confidence we can actually deliver another cycle of very strong growth over the next 10 years.

我們今天的公司和團隊與 10 年前有很大不同。看到我們所取得的進步和我們在產品組合中發展的優勢，以及公司人才的實力，真的很值得。我們今天在腫瘤學領域的運作方式與其他助教的運作方式非常非常不同。這讓我充滿信心，我們實際上可以在未來 10 年實現另一個非常強勁的成長週期。

So importantly, we delivered our upgraded guidance for the year, a 15% growth, excluding COVID, we had guided to increasing to low teens. So 15% is slightly better. On the EPS front, we grew by 15%, which is also slightly better than our upgraded guidance for the year. And in the quarter 4, we saw an opportunity because we had a tax benefit. We saw an opportunity to invest to drive further growth and stronger growth next year and the years after as we are launching new products and expanding our footprint.

重要的是，我們發布了今年升級的指導意見，即成長 15%（不包括新冠疫情），我們的指導意見是增加到十幾歲以下。所以15%稍微好一點。在每股盈餘方面，我們成長了 15%，這也略好於我們今年升級的指引。在第四季度，我們看到了機會，因為我們有稅收優惠。隨著我們推出新產品並擴大我們的足跡，我們看到了投資的機會，以推動明年和未來幾年的進一步成長和更強勁的成長。

You saw that the emerging markets out of China grew by 35%. China itself is rebounding and growing again. So China is back again on the growth trajectory and this year should be another good year. We've been improving our operating margin. You see a drop in '21, but that was -- it's a bit of an artifact because it's driven by the very large COVID sales we experienced. And of course, those were at no profit. So it dilutes our operating margin.

你看到中國以外的新興市場成長了35%。中國本身正在再次反彈和成長。因此，中國又回到了成長軌道，今年應該又是個好年。我們一直在提高營業利潤率。你會看到 21 年有所下降，但那是——這有點人為因素，因為它是由我們經歷的巨大的新冠病毒銷售推動的。當然，這些都是沒有利潤的。所以它稀釋了我們的營業利潤。

But essentially, you can see our continuous progress. And I wanted to say today that we are committed to our goals of mid-30s by -- in the midterm. And of course, long term, will be depending on our growth opportunities and our pipeline in particular. So we are doing 3 things. As I've said before, we are driving -- we are focusing on today. We're driving growth -- top line growth and operating margin. So we deliver our financial goals and that now is 2024 really.

但本質上，你可以看到我們不斷進步。今天我想說的是，我們致力於在中期實現 30 歲左右的目標。當然，從長遠來看，這將取決於我們的成長機會，特別是我們的管道。所以我們正在做三件事。正如我之前所說，我們正在前進——我們專注於今天。我們正在推動成長——收入成長和營業利潤率。所以我們實現了我們的財務目標，現在是 2024 年。

We're building the pipeline -- continuously building the pipeline so that we drive growth tomorrow, which is '25 to 2030. And we are investing in new technologies and new products to shape the future of medicine and drive long-term growth. And what I call long-term growth is what I often refer to as being the day after tomorrow, and it's '28, '29 and beyond. Ultimately, our goal is to remain a high-growth company for the next period of time, 10 years and beyond.

我們正在建造管道——不斷地建造管道，以便我們推動明天的成長，即「25年到2030年」。我們正在投資新技術和新產品，以塑造醫藥的未來並推動長期成長。我所說的長期成長就是我常所說的後天，也就是「28」、「29」及以後。最終，我們的目標是在未來十年及更長時間內保持高成長公司的地位。

You can see here that our revenue is spread across variety of therapy areas, but oncology, as you know, very well, biopharma, as you know very well and rare disease. And we had growth across all therapy areas. Oncology 21%, CVRM 18%, R&I 10%. Of course, V&I declined because we had a massive decline in COVID sales and rare disease grew by 12%, which is more than most people affected and actually more than we as expected. If you remember, we guided that we could grow by high single digit this rare disease business, but in fact, we're delivering low double-digit growth rate. And Mark will talk more about this.

您可以在這裡看到，我們的收入分佈在各個治療領域，但腫瘤學（如您所知）、生物製藥（如您所知）和罕見疾病。我們在所有治療領域都取得了成長。腫瘤學 21%，CVRM 18%，R&I 10%。當然，V&I 下降是因為我們的新冠肺炎銷售額大幅下降，而罕見疾病增長了 12%，這超過了大多數受影響的人，實際上也超過了我們的預期。如果你還記得的話，我們預計這個罕見疾病業務可以實現高個位數成長，但事實上，我們正​​在實現較低的兩位數成長率。馬克將更多地談論這一點。

All geographies did very well, 14% in the U.S., 20% in the emerging market, which is 35% ex China and 8% in China. And you can see here the growing importance of the emerging markets outside of China. In Europe, we grew by 17% and established rest of the world, 8%. Japan is starting to be impacted by the loss of exclusivity on Nexium, of course, but still 8% growth is a pretty nice number there. So again, well diversified growth across geographies and across our disease areas.

所有地區都表現出色，美國佔 14%，新興市場佔 20%，其中中國以外地區佔 35%，中國佔 8%。您可以在這裡看到中國以外的新興市場的重要性日益增長。在歐洲，我們成長了 17%，而世界其他地區則成長了 8%。當然，日本開始受到 Nexium 獨家經營權喪失的影響，但 8% 的成長仍然是一個相當不錯的數字。同樣，跨地域和跨疾病領域的多元化成長。

So tomorrow. So this is day after -- this is today and tomorrow is really the pipeline driving the pipeline. We guided earlier this year that we had a goal of 30 new Phase III. We've achieved 27, which is short by 3 that are a little bit delayed and starting in the early '24 instead of '23, but '27 is a very large number of Phase III starts. Importantly, 10 of those have a potential to be blockbusters either new products or new indications, blockbuster, of course, being more than $1 billion. So we have 10 of these Phase III trials that if they are successful, we'll deliver $1 billion sales or more each.

那麼明天。所以這是後天——這是今天，明天才是真正的管道驅動管道。今年早些時候，我們制定了 30 個新的 III 期目標。我們已經實現了 27 項，比 24 年初啟動的 3 個項目少了一些，而不是 23 年，但 27 年是第三階段啟動的一個非常大的數量。重要的是，其中 10 個有潛力成為重磅新產品或新適應症，當然，重磅產品的價值超過 10 億美元。因此，我們進行了 10 項 III 期試驗，如果它們成功，我們將為每項試驗帶來 10 億美元或更多的銷售額。

We also achieved 24 regulatory market -- regulatory approval across major markets. And finally, we got approval for 4 new medicines, and we are on track to deliver 15 new molecular entities, launches by 2030. And as you can see on this slide, those approvals, those new medicines range from biopharma with the Airsupra to oncology, with Truqap. Again, back to biopharm with Wainua, eplontersen and also rare diseases, Alexion with danicopan's Voydeya approval in PNH. So across the whole pipeline, we are launching new medicines.

我們還獲得了 24 個監管市場——跨主要市場的監管批准。最後，我們獲得了4 種新藥的批准，我們預計在2030 年之前推出15 種新分子實體。正如您在這張幻燈片上看到的，這些批准、這些新藥的範圍從Airsupra 的生物製藥到腫瘤學，與特魯卡普。再次回到生物製藥領域，Wainua、eplontersen 以及罕見疾病藥物 Alexion 和 danicopan 的 Voydeya 在 PNH 獲得批准。因此，在整個管道中，我們正在推出新藥。

And finally, what I call the day after tomorrow is really this new technologies built new platforms. And so what are we trying to do here? First of all, we have, we believe, a tremendous opportunity to leverage our growing pipeline of antibody drug conjugates with our IO bispecifics. So in the ADC space, we started with this collaboration with Daiichi Sankyo that you know very well. We've now built our own internal portfolio of ADCs. We have 6 ADCs that are totally owned by AstraZeneca with unique targets and unique warheads. And there's more to come. We can talk about it later, but we are working on multiple targets and warheads.

最後，我所說的後天其實是新技術建構的新平台。那我們在這裡想做什麼呢？首先，我們相信，我們有一個巨大的機會來利用我們不斷增長的抗體藥物偶聯物管道和 IO 雙特異性藥物。因此，在 ADC 領域，我們從與您非常了解的第一三共 (Daiichi Sankyo) 的合作開始。我們現在已經建立了自己的內部 ADC 產品組合。我們擁有阿斯特捷利康完全擁有的 6 個 ADC，具有獨特的目標和獨特的彈頭。還有更多的事情即將發生。我們可以稍後再討論，但我們正在研究多個目標和彈頭。

And finally, and importantly, we can combine those with our bispecifics, and we have 3 of those 2 that are more advanced and are very exciting products. And we believe in oncology, this ADC combination with IO can totally transform the way cancer is treated and position us as 1 of the few companies that has the potential to leverage this combinations.

最後，也是重要的是，我們可以將它們與我們的雙特異性產品結合起來，我們擁有這 2 種中的 3 種，它們更先進，是非常令人興奮的產品。我們相信，在腫瘤學領域，這種 ADC 與 IO 的組合可以完全改變癌症的治療方式，並使我們成為少數有潛力利用這種組合的公司之一。

We work on cell therapy because we believe cell therapy will be an important technology for the future. Today, those are mostly CAR-Ts in hematology. We want to take this into solid tumors, we want to take this into allogenic of the cell therapy. And we also want to take this into immune diseases, and we started working on this. So what we have been doing is leveraging our own internal efforts and our own internal technologies and combining this with putting together a series of technologies and platforms that has really the potential for us now to deliver what I was just talking about, which is moving into solid tumors, moving into allogeneic cell therapy and moving into immune diseases, and we now have a complete set of what we need. Now it's a question of integration and execution, but we have the technology that are required to achieve what our long-term goal is in cell therapy.

我們致力於細胞治療，因為我們相信細胞治療將成為未來的重要技術。如今，這些主要是血液學領域的 CAR-T。我們希望將其應用於實體腫瘤，我們希望將其應用於細胞療法的異體治療中。我們也想將其納入免疫疾病領域，我們開始研究這一點。因此，我們一直在做的是利用我們自己的內部努力和我們自己的內部技術，並將其與一系列技術和平台相結合，這些技術和平台現在確實有潛力讓我們實現我剛才所說的，這正在進入實體瘤，進入同種異體細胞療法並進入免疫疾病，我們現在擁有一整套我們需要的東西。現在是整合和執行的問題，但我們擁有實現細胞治療長期目標所需的技術。

And you've got listed here on Neogene, Quell, Cellectis, Gracell. And all of those together will enable us to build what we want to do in oncology and Biopharm. Another technology that we believe will shape the long-term is T cell engagers. And again, we've done that with our own internal effort and complemented with BD. The BD we do is not a random BD. It's always with a view to build a strong presence in some of the technologies we've identified, and we've done this with DC. We're doing it with cell therapy. We're doing it with T cell engagers. And finally, we do it in gene therapy with a focus on rare diseases.

您已在 Neogene、Quell、Cellectis、Gracell 上列出。所有這些共同將使我們能夠在腫瘤學和生物製藥領域實現我們想要做的事情。我們認為將影響長期發展的另一項技術是 T 細胞接合器。我們再次透過自己的內在努力做到了這一點，並輔以 BD。我們做的BD不是隨機的BD。我們始終致力於在我們已確定的一些技術中建立強大的影響力，我們已經透過 DC 做到了這一點。我們正在透過細胞療法來做到這一點。我們正在用 T 細胞接合者來做這件事。最後，我們在基因治療中進行這種治療，並專注於罕見疾病。

If you are in rare diseases, you really have to have a gene therapy approach complementing your portfolio. And of course, here, you know well, the Pfizer gene therapy portfolio acquisition and complemented with the Cellectis collaboration.

如果您患有罕見疾病，您確實必須有基因治療方法來補充您的投資組合。當然，在這裡，您很清楚，輝瑞收購了基因治療產品組合，並與 Cellectis 合作進行了補充。

So this is really what we believe is going to drive a little bit of midterm growth with Daiichi Sankyo's collaboration in some of the ADCs, but mostly looking at driving growth, '28, '29 and beyond, so we can deliver growth today, tomorrow and the day after.

因此，我們確實相信，透過第一三共在一些 ADC 中的合作，將推動一定程度的中期增長，但主要著眼於推動 28 年、29 年及以後的增長，因此我們可以在今天、明天實現增長以及後天。

So with this, I'll hand over to Aradhana, who's going to take you through the financials. Over to you.

因此，接下來我將把工作交給 Aradhana，他將帶您了解財務狀況。交給你了。

Thank you, Pascal. As usual, I will start with our reported P&L. As Pascal mentioned in his opening comments, total revenue increased 6% in 2023, which was at the top end of our updated guidance range. Product sales increased by 4% despite a decline of $3.8 billion in COVID-19 product sales in the year. Alliance revenue increased by 89%, driven by higher and HER2 sales in regions where Daiichi Sankyo books product sales.

謝謝你，帕斯卡。像往常一樣，我將從我們報告的損益表開始。正如 Pascal 在開場白中提到的那樣，2023 年總收入增長了 6%，這是我們更新的指導範圍的上限。儘管今年 COVID-19 產品銷售額下降了 38 億美元，但產品銷售額仍成長了 4%。受第一三共 (Daiichi Sankyo) 產品銷售地區的 HER2 銷量增加的推動，聯盟收入增加了 89%。

Turning to the core P&L. Our core product sales -- sorry. Our core product sales gross margins increased by 2 percentage points to 81.7%. This step-up in gross margin was driven by lower COVID-19 revenues in 2023. In 2024, we anticipate a slightly lower product sales gross margin percentage driven by higher sales in emerging markets increased before this product supply, higher production costs in certain facilities as well as higher product sales for partnered products and regions where we book sales and then pay out a profit share to our partners through cost of sales.

轉向核心損益表。我們的核心產品銷售—抱歉。核心產品銷售毛利率成長2個百分點至81.7%。毛利率的上升是由於2023 年COVID-19 收入下降所致。到2024 年，我們預計產品銷售毛利率將略有下降，原因是在此產品供應之前新興市場銷售額增加、某些設施的生產成本增加以及合作產品和地區的更高產品銷量，我們在這些地區預訂銷售，然後透過銷售成本向合作夥伴支付利潤分成。

Core operating costs increased by 9% in 2023. R&D costs increased by 9%, driven by 27 new Phase III starts in last year including multiple trials of our PD-1 CTLA-4 bispecific [more rustamic] and our oral SERD camizestrant. R&D cost as a percentage of total revenue was 22%, in line with our ambition. As expected, poor SG&A stepped up in the fourth quarter relative to the third quarter in 2023. We increased our investment in new launches behind Wainua, Truqap and Airsupra and continue to invest behind indications, expansions such as Farxiga in CKD and heart failure and Imfinzi across tumor types.

2023 年，核心營運成本增加了9%。研發成本增加了9%，這是由去年27 個新的III 期專案啟動推動的，其中包括我們的PD-1 CTLA-4 雙特異性[更rustamic]和我們的口服SERD 卡米司群的多項試驗。研發成本佔總收入的比例為 22%，符合我們的目標。正如預期的那樣，第四季度的SG&A 較2023 年第三季的表現較差。我們增加了對Wainua、Truqap 和Airsupra 背後的新產品的投資，並繼續投資於適應症、擴張，例如針對CKD 和心臟衰竭的Farxiga 和Imfinzi跨腫瘤類型。

Our full year core tax rate of 17% came in slightly below our guidance. The fourth quarter tax rate benefited from an adjustment to deferred taxes following an intra-group purchase of certain intellectual property, offset by unfavorable tax ruling in certain jurisdictions. Overall, our P&L allowed us to increase investments in both R&D and SG&A in the fourth quarter. Core EPS for the full year 2023 was $7.26, a growth of 15% versus the prior year.

我們的全年核心稅率為 17%，略低於我們的指引。第四季稅率受益於集團內部購買某些智慧財產權後對遞延稅項的調整，但被某些司法管轄區不利的稅務裁決所抵銷。總體而言，我們的損益表使我們能夠在第四季度增加研發和銷售、管理及管理方面的投資。 2023 年全年核心每股收益為 7.26 美元，較上年增長 15%。

As Pascal stated earlier, we have made good progress on both top and bottom line delivery in recent years, and we remain on track to deliver both industry-leading growth and improve operating margin to the mid-30s in the midterm, balanced by the need for continued investment to drive top line growth in both the near term and midterm and long term.

正如帕斯卡早些時候所說，近年來，我們在營收和利潤交付方面都取得了良好進展，並且我們仍然有望實現行業領先的增長，並在中期將營業利潤率提高到30 多歲，並根據需求進行平衡持續投資以推動近期、中長期收入成長。

Today, we are pleased to announce our 2024 full year guidance. We anticipate our total revenue of low double-digit to low teens percentage increase and our core EPS of low double digits to low teen percentage increase as well. Collaboration revenue is expected to increase substantially driven by success-based milestones and certain anticipated transactions. Other operating income, on the other hand, is anticipated to decrease substantially.

今天，我們很高興宣布 2024 年全年指引。我們預計我們的總收入將實現低兩位數至低青少年百分比的成長，我們的核心每股盈餘也將實現低兩位數至低青少年百分比的成長。在基於成功的里程碑和某些預期交易的推動下，協作收入預計將大幅成長。另一方面，其他營業收入預計將大幅下降。

Recall that in 2023, it included a one-off gain of around $700 million related to the renegotiated before test agreement and another $240 million related to the sale of [from the] court in the U.S. If FX rates for February to December were to remain at average rates seen in 2024 January, we anticipate a low single-digit adverse FX impact on both revenue and core EPS in 2024.

回想一下，2023 年，它包括與測試前重新談判協議相關的約 7 億美元一次性收益，以及與美國法院出售相關的另外 2.4 億美元收益（如果 2 月至 12 月的匯率保持不變）按照2024 年1 月的平均值計算，我們預期2024 年外匯對營收和核心每股盈餘的不利影響將僅為個位數。

Cash flow from operating activities increased by $537 million in 2023. We continue to focus on improving our cash conversion and have already made significant progress in this area. Deal payments amounted to approximately $4 billion, of which, nearly half related to past business development payments, including milestone payments to Daiichi Sankyo.

2023 年，經營活動產生的現金流量增加了 5.37 億美元。我們繼續專注於改善現金轉換，並已在該領域取得了重大進展。交易付款額約為 40 億美元，其中近一半與過去的業務開發付款有關，包括對第一三共的里程碑付款。

For this year, we again anticipate about $2 billion in deal payments relating to historical transactions. CapEx in 2023 was around $1.4 billion. In 2024, we anticipate a significant step-up in CapEx potentially in the 50% range, driven by investments in new manufacturing capabilities such as API, inhaled products and cell therapy. Our net debt at the end of 2023 was $22.5 billion, and given very recent BD transactions, totaling about $2 billion, we anticipate this to remain at about the same level in 2024.

今年，我們再次預計與歷史交易相關的交易付款約為 20 億美元。 2023 年的資本支出約為 14 億美元。到 2024 年，我們預計，在 API、吸入產品和細胞療法等新製造能力投資的推動下，資本支出可能大幅增加 50%。截至 2023 年底，我們的淨債務為 225 億美元，考慮到最近的 BD 交易總額約為 20 億美元，我們預計這一數字到 2024 年將保持在大致相同的水平。

With this in mind, our finance expense is expected to increase given the current interest rate environment. Our net debt to adjusted EBITDA ratio is 1.6x on the last 12-month basis. Our capital allocation priorities remain unchanged with our #1 priority to reinvest in the business, both in the pipeline and behind new launches. We remain committed to keeping a strong investment-grade rating and we'll continue to pursue value-enhancing business development transactions. Towards the end of last year, we announced a license agreement with Eccogene and the proposed acquisitions of Icosavax and Gracell. Finally, we maintain our progressive dividend policy defined as either a stable or increasing dividend.

考慮到這一點，考慮到當前的利率環境，我們的財務費用預計會增加。在過去 12 個月的基礎上，我們的淨負債與調整後 EBITDA 的比率為 1.6 倍。我們的資本配置優先事項保持不變，我們的第一優先事項是對業務進行再投資，無論是在管道中還是在新產品推出後。我們仍致力於維持強勁的投資等級評級，並將繼續尋求增值業務發展交易。去年年底，我們宣布與 Eccogene 達成授權協議，並擬收購 Icosavax 和 Gracell。最後，我們維持漸進式股利政策，定義為穩定或增加股利。

With that, I will hand over to Dave.

這樣，我將把工作交給戴夫。

Thanks, Aradhana. Really appreciate that. So oncology total revenues of $18.4 billion in the full year period grew 21% versus the prior year, and that was driven by strong global demand of our key medicines. Tagrisso global revenues grew 6% in the fourth quarter, reflecting strong double-digit growth for the U.S. and Europe.

謝謝，阿拉達納。真的很感激。因此，全年腫瘤學總收入為 184 億美元，比上年增長 21%，這是由全球對我們的關鍵藥物的強勁需求推動的。泰瑞沙第四季全球營收成長 6%，反映出美國和歐洲的強勁兩位數成長。

Performance in the quarter was partially offset by continued impact from the June 2023 mandatory price reduction in Japan, as well as expected impact from hospital ordering dynamics in China and a rebate reclassification in Australia.

本季的業績被日本 2023 年 6 月強制降價的持續影響、中國醫院訂購動態和澳洲回扣重新分類的預期影響所部分抵消。

In the fourth quarter, Lynparza delivered 8% product sales growth and remains the leading PARP inhibitor globally despite ongoing class challenges. In the period, we recognized $245 million in regulatory milestones from Merck, following the U.S. [PROPEL] approval and BRCA-mutated prostate cancer. Imfinzi, inclusive of Imjudo grew 52% in the fourth quarter, fueled by further global demand growth in gastrointestinal tumors.

儘管面臨持續的類別挑戰，奧拉帕尼第四季的產品銷售額成長了 8%，仍然是全球領先的 PARP 抑制劑。在此期間，在美國 [PROPEL] 批准和 BRCA 突變前列腺癌治療之後，我們認識到默克公司在監管方面取得了 2.45 億美元的里程碑。在全球胃腸道腫瘤需求進一步增長的推動下，包括 Imjudo 在內的 Imfinzi 在第四季度增長了 52%。

In 2024, we expect continued progress with TOPAZ-1 and HIMALAYA although TOPAZ-1 demand in the U.S. will moderate as the regimen is now established as the clear standard of care. In Japan, a 25% price reduction based on sales took effect in February of this year. An additional mandatory price reduction is anticipated later this year based on recent fixed dosing approvals.

到 2024 年，我們預計 TOPAZ-1 和 HIMALAYA 將繼續取得進展，儘管隨著該方案現已被確立為明確的護理標準，美國對 TOPAZ-1 的需求將會放緩。在日本，今年 2 月開始根據銷售降價 25%。根據最近固定劑量的批准，預計今年稍後將進一步強制降價。

Calquence total revenues increased 14% in the fourth quarter, driven by continued new patient share gains across both frontline and relapsed/refractory CLL. In HER2 total revenues of $364 million in the fourth quarter increased 68% year-on-year. In the U.S. and Germany, we're very encouraged by new patient share gains in the HER2-positive setting firmly establishing in HER2 is the undisputed standard of care across HER2-positive and HER2 low metastatic breast cancer.

在第一線和復發/難治性 CLL 的新患者份額持續增長的推動下，Calquence 第四季度總收入增長了 14%。 HER2第四季總營收為3.64億美元，年增68%。在美國和德國，我們對 HER2 陽性環境中新患者份額的增加感到非常鼓舞，因為 HER2 是 HER2 陽性和 HER2 低轉移性乳癌無可爭議的護理標準。

In November of last year, we received approval for Truqap, our novel AKT inhibitor in the U.S. and for Imfinzi TOPAZ-1 in China. Importantly, we received a priority review designation for an HER2 and HER2-expressing tumors an adjuvant use of Tagrisso was added for the first time to the NRDL in China at no discount.

去年 11 月，我們的新型 AKT 抑制劑 Truqap 在美國獲得批准，Imfinzi TOPAZ-1 在中國獲得批准。重要的是，我們獲得了針對 HER2 和 HER2 表達腫瘤的優先審查資格，Tagrisso 的輔助用藥首次被無折扣地納入中國國家醫保目錄。

With the exciting approval of Truqap, we have the opportunity to further extend our leadership in breast cancer, including in the hormone receptor positive landscape. And HER2 is the established standard of care in late-line HER2 low, and we look forward to the results of the DESTINY-Breast06 trial in the first half of this year and the opportunity to bring in HER2 1 line earlier and expand into HER2 ultra-low tumors. Data from the TROPION-Breast01 trial of Dato-DXd in hormone receptor positive HER2 low breast cancer was presented at ESMO last year during the presidential symposium. Discussions with health authorities and prelaunch planning activities are already well underway.

隨著 Truqap 獲得令人興奮的批准，我們有機會進一步擴大我們在乳癌領域的領導地位，包括在荷爾蒙受體陽性領域。而 HER2 是晚期 HER2 low 的既定護理標準，我們期待今年上半年 DESTINY-Breast06 試驗的結果，以及更早引入 HER2 1 線並擴展到 HER2 ultra 的機會-低腫瘤。去年在 ESMO 主席研討會上公佈了 Dato-DXd 治療荷爾蒙受體陽性 HER2 低乳癌的 TROPION-Breast01 試驗數據。與衛生當局的討論和啟動前的規劃活動已經在順利進行。

Finally, inline with our ambition to establish a new endocrine therapy backbone, we now have several pivotal trials ongoing in the frontline for our next-generation oral SERD camizestrant, including in combination with CDK4/6 inhibitors and Truqap. Truqap is being very well received by the clinical community in the United States, and we are already seeing rapid adoption with the majority of new starts in patients with biomarker altered tumors, who have previously received a CDK4/6 inhibitor, which is consistent with our views of the addressable population. We see potential for Truqap to become the new standard of care in second line for endocrine treated patients with PIK3CA, AKT1 or PTEN altered tumors. And with that, we'll advance to the next slide, and I'll hand over to Susan to cover R&D highlights in the quarter.

最後，為了符合我們建立新的內分泌治療支柱的雄心，我們現在正在一線進行下一代口服 SERD camizestrant 的幾項關鍵試驗，包括與 CDK4/6 抑製劑和 Truqap 的組合。 Truqap 受到美國臨床界的廣泛好評，我們已經看到大多數生物標記改變的腫瘤患者在新開始治療時得到了快速採用，這些患者之前接受過CDK4/6 抑製劑，這與我們的研究結果一致。可尋址人群的觀點。我們認為 Truqap 有潛力成為接受內分泌治療的 PIK3CA、AKT1 或 PTEN 改變腫瘤患者二線治療的新標準。接下來，我們將進入下一張投影片，我將交給 Susan 介紹本季的研發亮點。

Thank you, Dave. In December, we entered into a definitive agreement to acquire Gracell Technologies, which furthers our cell therapy ambition across oncology and autoimmune diseases. Gracell has a proprietary cell therapy manufacturing platform called FasTCAR. The FasTCAR platform has several key benefits. First, it significantly reduces the manufacturing time from between 1 and 3 weeks to 22 to 36 hours, with the opportunity to improve medium turnaround time, and also enable increased manufacturing capacity as well as predictability of CAR-T delivery.

謝謝你，戴夫。 12 月，我們達成了收購 Gracell Technologies 的最終協議，進一步推進了我們在腫瘤學和自體免疫疾病領域的細胞治療雄心。 Gracell 擁有名為 FasTCAR 的專有細胞治療製造平台。 FasTCAR 平台有幾個關鍵優勢。首先，它將製造時間從 1 至 3 週顯著縮短至 22 至 36 小時，從而有機會縮短中期週轉時間，並提高製造能力以及 CAR-T 交付的可預測性。

Second, a lower dose of cells need to be manufactured for each patient, which reduces the risk of cytokine release syndrome, and that can improve the safety profile. And third, the shorter manufacturing time delivers fitter T cells, and this potentially improves the efficacy of this CAR-T. This proposed acquisition also enriches our growing pipeline of cell therapies with GC012F, a novel clinical stage dual BCMA and CD19 targeting autologous CAR-T.

其次，需要為每位患者生產較低劑量的細胞，這降低了細胞激素釋放症候群的風險，並且可以提高安全性。第三，更短的製造時間可以提供更適合的 T 細胞，這可能會提高 CAR-T 的功效。此次擬議的收購也豐富了我們不斷成長的 GC012F 細胞療法產品線，GC012F 是一種新型臨床階段雙 BCMA 和 CD19 靶向自體 CAR-T。

Phase I data presented at the ASH meeting in December. In 22 patients with newly diagnosed high-risk multiple myeloma, the objective response rate was 100%, and we saw a minimal residual disease negativity rate between 95% and 100%, 6 to 12 months after infusion.

第一階段數據在 12 月的 ASH 會議上公佈。在 22 名新診斷的高風險多發性骨髓瘤患者中，客觀緩解率為 100%，輸注後 6 至 12 個月，微小殘留疾病陰性率在 95% 至 100% 之間。

This demonstrates the promise of this potential therapy when you move it into an earlier line setting. Safety was also favorable with only 27% of patients experiencing either grade 1 or 2 cytokine release syndrome and no grade 3 or above events. Additionally, we did not see any neurological toxicity, which can be associated with this type of therapy. With a median follow-up time of 18.8 months median PFS and median duration of response had not been reached also highlighting the durability of the response.

這證明了當您將其轉移到較早的生產線設定時，這種潛在療法的前景。安全性也很好，只有 27% 的患者經歷 1 級或 2 級細胞激素釋放綜合徵，並且沒有 3 級或以上事件。此外，我們沒有發現任何與此類治療相關的神經毒性。中位追蹤時間為 18.8 個月，中位 PFS 和中位緩解持續時間尚未達到，也凸顯了緩解的持久性。

We believe that GC012F has potential applications across hematologic malignancies, including multiple myeloma and will further bolster our hematology pipeline, adding to Calquence AZD0486, our CD19 CD3 next-generation bispecific T cell engager and AZD0305, our GPRC5D targeting antibody drug conjugate.

我們相信，GC012F 在包括多發性骨髓瘤在內的血液系統惡性腫瘤中具有潛在的應用前景，並將進一步增強我們的血液學產品線，加入我們的CD19 CD3 下一代雙特異性T 細胞接合劑Calquence AZD0486 和我們的GPRC5D 標靶抗體藥物偶聯物AZD0305 中。

We also have 2 further homegrown hematology molecules, which have just entered the clinic. A CD123 antibody drug conjugate, AZD9829 and a PRMT5 inhibitor AZD3470. We look forward to updating you on our exciting hematology pipeline over the course of this year. And with that, can you please advance to the next slide, and I'll pass over to Ruud to cover bio-pharmaceuticals performance.

我們還有另外兩種本土血液學分子，剛進入臨床。 CD123 抗體藥物綴合物 AZD9829 和 PRMT5 抑制劑 AZD3470。我們期待今年向您介紹我們令人興奮的血液學產品線的最新情況。那麼，請您轉到下一張投影片，我將由 Ruud 介紹生物製藥的業績。

Thank you so much, Susan. Bio-pharmaceuticals delivered total revenue of $18.4 billion in 2023, driven by growth of 18% in CVRM and 10% in R&I. Key highlights for the year included Farxiga nearing $6 billion in total revenue and R&I returning to double-digit growth.

非常感謝你，蘇珊。在 CVRM 成長 18% 和 R&I 成長 10% 的推動下，生物製藥在 2023 年實現總收入 184 億美元。今年的主要亮點包括 Farxiga 總營收接近 60 億美元，研發與創新恢復兩位數成長。

Turning now to the fourth quarter, where within R&I, nearly half of the total revenue came from Fasenra, Tezspire, Saphnelo and Breztri. These medicines grew by a combined 40% more than offsetting the impact of Symbicort generic entry. And in V&I, Beyfortus continued to see strong demand in its first RSV season, generating $95 million of product sales and alliance revenue for AstraZeneca in the quarter. Lastly, we received our first sales related milestone payments from Sanofi totaling $27 million.

現在轉向第四季度，在 R&I 內部，總收入的近一半來自 Fasenra、Tezspire、Saphnelo 和 Breztri。這些藥物的成長總計 40%，超過了 Symbicort 仿製藥進入市場的影響。在 V&I 中，Beyfortus 在其第一個 RSV 季節中繼續看到強勁的需求，本季為阿斯特捷利康創造了 9,500 萬美元的產品銷售額和聯盟收入。最後，我們從賽諾菲收到了第一筆與銷售相關的里程碑付款，總額為 2700 萬美元。

We have recently launched 3 innovative new medicines within biopharmaceuticals. Launches in new areas of science and medicine require us to raise awareness among patients and practitioners and often to build additional sales forces, maximizing early momentum for these launch brands is critical to delivering on their full potential. Eplontersen is an amyloidosis treatment that we are developing in partnership with Ionis. In January, it launched with the brand-new Wainua for patients with ATTR polyneuropathy, a debilitating ultra rare disease, which is generally fatal within a decade if left and treated.

我們最近推出了 3 種生物製藥領域的創新新藥。在新的科學和醫學領域推出產品需要我們提高患者和從業者的意識，並經常建立額外的銷售隊伍，最大限度地提高這些推出品牌的早期動力對於充分發揮其潛力至關重要。 Eplontersen 是我們與 Ionis 合作開發的一種澱粉樣變性治療方法。一月份，該公司推出了全新的 Wainua，用於治療 ATTR 多發性神經病患者，這是一種使人衰弱的極其罕見的疾病，如果不治療並接受治療，通常會在十年內致命。

Airsupra is the first rescue medicine to reduce exacerbation and treat the underlying inflammation. And we have shown with the MANDALA trial, a 28% reduction in the risk of severe asthma exacerbations in adult patients compared to albuterol. We formally launched Airsupra last month for adult patients. And over time, we hope to see primary care physicians in the United States changed 50 years of prescribing habits. As mentioned, we are off to a strong start and are only halfway through the first RSV season that Beyfortus has been available for infants.

Airsupra 是第一種減少病情惡化和治療潛在發炎的救援藥物。我們透過 MANDALA 試驗證明，與沙丁胺醇相比，成年患者氣喘嚴重發作的風險降低了 28%。上個月，我們正式為成年患者推出了 Airsupra。隨著時間的推移，我們希望看到美國的初級保健醫生改變 50 年來的處方習慣。如前所述，我們有了一個良好的開端，而 Beyfortus 可供嬰兒使用的第一個 RSV 季節才剛剛過半。

Following continued strong demand and the recent approval in China, we are planning for a substantial increase in capacity in 2024. We continue to invest behind the Farxiga brands with growth being driven across the global -- across the globe by recent launches in heart failure and chronic kidney disease.

鑑於持續強勁的需求以及最近在中國獲得批准，我們計劃在 2024 年大幅增加產能。我們將繼續投資 Farxiga 品牌，並透過最近推出的心臟衰竭和心臟衰竭藥物在全球範圍內推動增長。慢性腎病。

In the coming years, we aim to continue to build on this franchise with new combination medicines in development that address unmet needs in hypertension, heart failure and CKD, and with additional enemies in our late-stage and early-stage pipeline. Our CVRM portfolio is set to expand and evolve over the mid- to long term.

未來幾年，我們的目標是繼續在這項特許經營權的基礎上開發新的組合藥物，解決高血壓、心臟衰竭和慢性腎臟病方面未滿足的需求，並在我們的後期和早期管道中增加更多的敵人。我們的 CVRM 產品組合將在中長期內擴展和發展。

We recently commenced a Phase III trials for baxdrostat in uncontrolled and resistant hypertension as well as for zibotentan, combined with dapagliflozin, addressing patients with CKD and high proteinuria. Eplontersen is also being evaluated for the treatment of ATTR cardiomyopathy, which is estimated to affect up to 0.5 million patients worldwide. Our Phase III cardio transform trial is the largest of its kinds and is powered to show a cardiovascular mortality benefit, and we are very pleased to share today that we have obtained Fast Track designation from the FDA for our cardiomyopathy regulatory file.

我們最近開始了一項 III 期試驗，baxdrostat 治療不受控制的頑固性高血壓，以及 zibotentan 與達格列淨聯合治療 CKD 和高蛋白尿患者。 Eplontersen 也正在評估 ATTR 心肌病變的治療效果，估計該疾病影響全球多達 50 萬名患者。我們的 III 期心臟轉化試驗是同類試驗中規模最大的，能夠顯示心血管死亡率方面的益處，今天我們非常高興地與大家分享，我們的心肌病監管文件已獲得 FDA 的快速通道指定。

I will now hand over to Sharon to present the latest development from the biopharma pipeline.

現在我將請 Sharon 介紹生物製藥管道的最新進展。

Thank you so much, Ruud. I wanted to take this opportunity to highlight our current portfolio in immunology as well as provide more color on our recent business development deals focused on immune-mediated disease. In Saphnelo's, pivotal Phase III TULIP trials in systemic lucerathermatosis, we saw positive changes in cutaneous lupus. We are building on this and expanding into new indications. We have started enrolling patients in our Phase III DAISY trial of Saphnelo in patients with systemic sclerosis, a chronic disease characterized by diffuse fibrosis and vascular abnormalities in the skin, joints and internal organs, which can be fatal.

非常感謝你，路德。我想藉此機會強調我們目前在免疫學方面的產品組合，並為我們最近專注於免疫介導疾病的業務開發交易提供更多資訊。在 Saphnelo 針對系統性 lucerathermatosis 的關鍵 III 期 TULIP 試驗中，我們看到了皮膚狼瘡的正面變化。我們正在以此為基礎並擴展到新的適應症。我們已經開始在 Saphnelo 的 III 期 DAISY 試驗中招募患有系統性硬化症的患者，這是一種以皮膚、關節和內臟器官瀰漫性纖維化和血管異常為特徵的慢性疾病，可能是致命的。

We also have plans to initiate 2 other Saphnelo Phase III trials this year in cutaneous lupus and myositis. Our recent business development deals have accelerated our ambitions in immune-mediated diseases. Emerging data from Dr. [Seth's] academic group has shown the potential for long-term relation with CAR-Ts in systemic lupus erythematosus. Part of our definitive agreement to acquire Gracell includes autologous CAR-Ts with an ongoing Phase I investigator-initiated trial with GC012S, the C19 and BCMA CAR-T in 15 Chinese patients with SLA. We look forward to sharing the Phase I data at an upcoming conference.

我們也計劃今年啟動另外 2 項 Saphnelo III 期試驗，用於治療皮膚狼瘡和肌炎。我們最近的業務發展交易加速了我們在免疫介導疾病領域的雄心壯志。 [Seth] 博士學術小組的最新數據表明，CAR-T 在系統性紅斑狼瘡治療中具有長期關係的潛力。我們收購亙喜生物的最終協議的一部分包括自體 CAR-T，以及正在進行的 I 期研究者發起的 GC012S、C19 和 BCMA CAR-T 試驗，試驗對象為 15 名中國 SLA 患者。我們期待在即將舉行的會議上分享第一階段的數據。

Our collaboration with Quell is designed to develop multiple engineered T regulatory cell therapies, which have the potential to be transformative in type 1 diabetes and inflammatory bowel diseases. TReg cell therapies have a unique approach of modulating the immune system to reduce inflammation and prevent immune-mediated damage to tissues. Quell's innovative platform of armored TReg's could enable sustained clinical benefit.

我們與 Quell 的合作旨在開發多種工程 T 調節細胞療法，這些療法有可能為第 1 型糖尿病和發炎性腸道疾病帶來變革。 TReg 細胞療法具有獨特的調節免疫系統的方法，以減少發炎並防止免疫介導的組織損傷。 Quell 的裝甲 TReg 創新平台可實現持續的臨床效益。

And finally, our collaboration with Cellectis allows us to explore the potential of an allogeneic CAR-T platform. Off-the-shelf availability from allogeneic CAR-T cells is expected to reduce the time and cost associated with manufacturing. With these innovative transformational cell therapies as well as our internal capabilities, we are building a platform for a pipeline in immune-mediated diseases with transformative potential. I will now hand over to Marc, who will cover our rare disease portfolio.

最後，我們與 Cellectis 的合作使我們能夠探索同種異體 CAR-T 平台的潛力。同種異體 CAR-T 細胞的現成可用性預計將減少與製造相關的時間和成本。憑藉這些創新的轉化細胞療法以及我們的內部能力，我們正在建立一個平台，用於具有轉化潛力的免疫介導疾病的管道。現在我將把工作交給 Marc，他將負責我們的罕見疾病投資組合。

So thank you, Sharon. And for rare disease, the total revenue achieved $7.8 billion in 2023, up 12% year-over-year driven by growth in neurology indications, increased patient demand and launches in new markets. In the quarter, Ultomiris grew 38% and plus 52% for the full year, driven by neurology indication with the vast majority of growth coming from generalized mastenagravis patients were naive to branded treatments. As previously indicated, Ultomiris revenues were broadly in line with Soliris for the year. But if you look at the fourth quarter, Ultomiris revenues exceeded Soliris. .

謝謝你，莎倫。對於罕見疾病，由於神經學適應症的增長、患者需求的增加以及新市場的推出，2023 年總收入達到 78 億美元，年增 12%。在神經病學適應症的推動下，Ultomiris 在本季度增長了 38%，全年增長了 52%，其中絕大多數增長來自對品牌治療不熟悉的全身性乳房重症患者。如前所述，Ultomiris 今年的收入與 Soliris 基本一致。但如果你看看第四季度，Ultomiris 的收入超過了 Soliris。 。

Our conversion strategy is progressing well with the majority of patients already converted across PHN, a typical haemolytic uraemic syndrome and gMG in our major markets. We continue to launch both medicines globally and expect the C5 franchise, Soliris and Ultomiris revenues to remain sustainable and durable. Beyond complement, both Strensiq and Koselugo grew 13% and 48%, respectively, driven by continued patient demand.

我們的轉換策略進展順利，大多數患者已經在我們的主要市場中完成了 PHN（一種典型的溶血性尿毒症候群和 gMG）的轉換。我們將繼續在全球推出這兩種藥物，並預計 C5 特許經營權、Soliris 和 Ultomiris 收入將保持可持續和持久。除了補充之外，在患者持續需求的推動下，Strensiq 和 Koselugo 分別成長了 13% 和 48%。

I'm also delighted to announce that we have started enrolling patients in our Phase III trials for translating amyloid cardiomyopathy as well as for hypophosphatasia. ALXN2220 is a monoclonal antibody designed to deplete toxic amyloid fibrils in the heart with the potential to treat TTR cardiomyopathy in combination with standard of care stabilizes or silences.

我還很高興地宣布，我們已經開始招募患者參加轉化澱粉樣心肌病變和低磷酸酯酶症的 III 期試驗。 ALXN2220 是一種單株抗體，旨在消除心臟中有毒的澱粉樣原纖維，與穩定或沉默標準護理相結合，有可能治療 TTR 心肌病變。

Our Phase III trial is recruiting a broad range of patients with moderate and severe disease. It has been designed with hard cardiovascular endpoints all-cause mortality and cardiovascular events, which are extremely important for patients and clinicians as well as for regulators and payers.

我們的 III 期試驗正在招募廣泛的中度和重度疾病患者。它的設計考慮了硬心血管終點全因死亡率和心血管事件，這對於患者和臨床醫生以及監管機構和付款人來說極為重要。

We have begun enrollment in our Phase III program, with efzimfotasealfa, (inaudible) including 2 trials in the pediatric setting, investing both naive and switch patients as well as a larger trial in naive adults and adolescents. These trials represent a broad set of hypophosphatasia patients, including those with both skeletal and functional improvements. We believe that this product with every 2-week dosing and lower volume injections, coupled with improved manufacturing creates a significant opportunity to increase the addressable population by 3x as compared to Strensiq. We have made great progress in our late-stage pipeline with 9 Phase III programs underway and our 10th program, Ultomiris in IgAN is initiating soon.

我們已經開始註冊 efzimfotasealfa 的 III 期計畫（聽不清楚），其中包括 2 項兒科試驗，投資於初治患者和轉換患者，以及一項針對初治成人和青少年的更大規模試驗。這些試驗代表了廣泛的低磷酸酯酶症患者，包括骨骼和功能都有改善的患者。我們相信，與 Strensiq 相比，該產品每 2 週給藥一次並減少注射量，再加上製造的改進，創造了將目標族群增加 3 倍的重大機會。我們的後期研發管線取得了巨大進展，9 個 III 期計畫正在進行中，第 10 個計畫 Ultomiris in IgAN 即將啟動。

With that, I'm please announce -- will get to Pascal.

說到這裡，我請宣布——我將聯繫帕斯卡。

Thank you, Marc. If I move to the last slide. This is really to show you that over the next few months, we have quite a number of catalysts that are going to drive us across oncology, biopharm, but also rare diseases. And you have a few here that are listed. Of course, a number are missing. We also have FLAURA2 that will deliver updated OS data in the course of 2024.

謝謝你，馬克。如果我轉到最後一張投影片。這實際上是為了向您表明，在接下來的幾個月裡，我們有相當多的催化劑將推動我們跨越腫瘤學、生物製藥以及罕見疾病。這裡列出了一些。當然，還有一些數字缺失了。我們還有 FLAURA2，將在 2024 年提供更新的作業系統資料。

But some of the most important once they are going to drive the growth of several of our important products, LAURA for Tagrisso, DESTINY-Breast06 driving an HER2, TROPION-Breast02 with Dato-DXd, the WAYPOINT study, studying Tezspire and Chronic Rhinosinusitis with Nasal Polyps, and finally, EMERALD-2 Imfinzi. But there is, of course, a lot more than this.

但其中一些最重要的一旦它們將推動我們幾個重要產品的增長，LAURA for Tagrisso、驅動 HER2 的 DESTINY-Breast06、TROPION-Breast02 與 Dato-DXd、WAYPOINT 研究、研究 Tezspire 和慢性鼻竇炎鼻息肉，最後是EMERALD-2 Imfinzi。但當然，還有更多的事情。

The other point I wanted to make in conclusion is that the midterm pipeline is actually emerging very rapidly. We have some very good data coming up out of our bispecifics portfolio, and there will be more data points communicated in the course of this year. Our ADCs will have more data also to share about our ADCs and how this pipeline is shaping up. We have an emerging metabolism portfolio that we don't talk much yet, but is actually progressing very nicely. We have a very exciting old PCSK9 that is making good progress.

我想總結的另一點是，中期管道實際上正在非常迅速地出現。我們從雙特異性藥物組合中獲得了一些非常好的數據，今年也將傳達更多數據點。我們的 ADC 也將分享更多有關我們的 ADC 以及該管道如何形成的數據。我們有一個新興的新陳代謝產品組合，我們還沒有談論太多，但實際上進展得非常好。我們有一個非常令人興奮的舊 PCSK9，它正在取得良好的進展。

Baxdrostat is for hypertension is in Phase III. And finally, we have, of course, the oral GLP-1 agent, we license then and the beauty about those agents is that they can be combined. They can be combined with ADC, they come be combined between themselves. And so we have here a metabolism portfolio that is really starting to take good shape. And beyond the products as I mentioned, there's more to come, of course, in obesity but also in cardiovascular -- in heart disease and in renal disease.

Baxdrostat 用於治療高血壓，目前處於 III 期階段。最後，當然，我們還有口服 GLP-1 藥物，我們隨後獲得許可，這些藥物的優點在於它們可以組合使用。它們可以與ADC組合，它們之間可以組合。所以我們這裡的新陳代謝組合確實開始形成良好的狀態。除了我提到的產品之外，當然還有更多的產品，不僅針對肥胖，而且還針對心血管疾病——心臟病和腎臟疾病。

Cell therapy, we will -- this year, communicate some of the results of mid-stage studies progression. And finally, we will also be communicating information about our new DDA pipeline, and in particular, the PARP1 selective. So as you can see here, quite a lot of new data coming up, both from the Phase III pipeline but also from mid-stage pipeline that will give you a sense for what is coming up and why we believe -- why we are so excited, why we believe we can continue to drive top line growth over the next 10 years. And drive improvement in profitability as a result of this. Finally, I want to invite you all to our R&D Day. This will be in Cambridge at the DISC, our new R&D center.

細胞療法，我們將在今年公佈中期研究進展的一些結果。最後，我們也將傳達有關新 DDA 管道的訊息，特別是 PARP1 選擇性的訊息。正如您在這裡看到的，大量新數據即將出現，既有來自第三階段管道的數據，也有來自中期管道的數據，這將使您了解即將發生的事情以及我們為何相信——為什麼我們如此很興奮，為什麼我們相信我們可以在未來10 年繼續推動營收成長。並由此推動獲利能力的提升。最後，我想邀請大家參加我們的研發日。這將在劍橋的 DISC，我們的新研發中心進行。

You will see, as you -- for those of you who join us on the 21st of May, you will see this is a fantastic site, and our teams are very excited to be there, and I'm sure it will drive further momentum in our R&D productivity. The reason we do this R&D day is, as I said before, we've just completed our 10-year journey that we started in 2014. We're engaging in the next phase of our journey in the next 10 years. And we thought it's a good time to sit back and update our strategy and show you why we are so confident that the future is bright for AstraZeneca.

您將會看到，對於 5 月 21 日加入我們的人來說，您會發現這是一個很棒的網站，我們的團隊非常高興能夠來到這裡，我相信這將推動進一步的發展勢頭我們的研發生產力。我們舉辦這個研發日的原因是，正如我之前所說，我們剛剛完成了從 2014 年開始的 10 年旅程。我們將在未來 10 年中進入下一階段的旅程。我們認為現在是坐下來更新我們策略的好時機，並向您展示為什麼我們對阿斯特捷利康的未來充滿信心。

So with this, I'll stop here and then open the floor for questions.

因此，我就講到這裡，然後開始提問。

James Gordon from JPMorgan. I'll do just 2 questions, please. The first 1 was on revenues for this year. So the guidance, low double-digit or low teens as a revenue target, but I think bears are worried that lots of that is collaboration revenues growing and product sales slowing. So can you just say, is that fair? Do you also think that you can sustain the same sort of pace of product sales growth? Or is it really about collaboration revenues taking over from product sales. That's the first question, please.

摩根大通的詹姆斯戈登。我只回答 2 個問題。第一個是今年的收入。因此，指導方針將低兩位數或低十幾歲的收入目標作為收入目標，但我認為空頭擔心其中很大一部分是合作收入成長和產品銷售放緩。那你能說，這公平嗎？您是否也認為您可以維持同樣的產品銷售成長速度？或者這真的是關於從產品銷售中接手協作收​​入嗎？這是第一個問題，請。

And then I think the second question, the other thing that some bears have said today is that the top line guidance is about the same pace as the bottom line guidance. So that would imply then that margins might be about flat. And then I've seen, I think in Slide 6, you said that the -- in the medium-term margins will get to the mid-30s. But does that mean margins will be flat this year and then have to have a big inflection in '25 and '26 to get there? So thoughts on that and whether there is going to be a lot more OpEx and how that's going to work, please?

然後我認為第二個問題，一些空頭今天所說的另一件事是，頂線指導與底線指導的步伐大致相同。因此，這意味著利潤率可能會持平。然後我看到，我想在幻燈片 6 中，您說過中期利潤率將達到 30 多歲。但這是否意味著今年的利潤率將持平，然後必須在 25 年和 26 年出現大幅變化才能實現這一目標？那麼對此有何想法，是否會有更多的營運支出以及如何運作？

Thank you, James. Great questions. And I know you will open the floor, I'm sure. But let me just be very categorical here. Our product sales are going to grow very strongly. So the collaboration revenue, of course, are adding to that growth. But certainly, product sales are very much on track to deliver the kind of growth that is included in the guidance range that we are communicating.

謝謝你，詹姆斯。很好的問題。我確信您會發言。但讓我在這裡非常明確地說。我們的產品銷售將會非常強勁地成長。因此，合作收入當然會促進這種成長。但可以肯定的是，產品銷售非常有望實現我們正在溝通的指導範圍內的成長。

Yes. I mean if you look at just, for example, the growth in 2023 across the franchises, right, with oncology growing 21%, rare disease, 12, 18% in CVRM. So we -- again and all of that is from current products. So we expect that that momentum to continue into the coming year. Obviously, different products have different sort of dynamics and so forth. So the growth will come in product sales from both current products as well as some of the new launches that we have, though, again, they're early in their launch trajectory.

是的。我的意思是，例如，如果你看一下 2023 年各特許經營業務的增長，對吧，腫瘤學增長 21%，罕見疾病增長 12%，CVRM 增長 18%。所以我們再次強調，所有這些都來自當前的產品。因此，我們預計這種勢頭將持續到明年。顯然，不同的產品有不同的動態等等。因此，成長將來自當前產品以及我們推出的一些新產品的產品銷售，儘管它們再次處於發布軌蹟的早期。

I think on your second question, so when we have given obviously a range on both top line and bottom line. But some of the other elements that I mentioned in my prepared remarks. One was, for example, the finance expense that we expect slightly to go up given the transactions that we did towards the end of last year and so forth and refinancing for some of the debt that we have. The second element is we obviously benefited a little bit from the tax rate last year. So that tax rate benefit will also not be there.

我想關於你的第二個問題，所以當我們在頂線和底線上顯然給出了一個範圍時。但我在準備好的發言中提到了一些其他要素。例如，考慮到我們去年年底等進行的交易以及我們所擁有的一些債務的再融資，我們預計財務費用會略有上升。第二個因素是我們去年顯然從稅率中受益了一些。因此，稅率優惠也不會存在。

So if you look at the totality of the P&L, those will also be elements and we get to the range that we have on EPS. And when you take that into account, obviously, we expect the revenue growth to, we be pretty strong, but the operating expense growth to be lagging the revenue growth. And that's what's operating leverage.

因此，如果你看一下損益表的整體情況，這些也將是要素，我們就會得到每股盈餘的範圍。考慮到這一點，顯然，我們預計收入成長將相當強勁，但營運費用成長將落後於收入成長。這就是經營槓桿。

Emily Field from Barclays. I have a couple of questions on oncology. The first on Dato-DXd or AVANZAR study must have enrolled pretty quickly to be having a readout in 2025. Is that what you were to be positive, would you file based on that study? I know it's designed somewhat differently to TL07 and 08? And then on HER2 for DESTINY-Breast06, how much does the inclusion of the ultra low population expand the addressable patient set? I think you've said before that HER2 low is about 50% of breast cancers. How much bigger does that get with HER2 ultra-low?

巴克萊銀行的艾米麗·菲爾德。我有幾個關於腫瘤學的問題。第一項關於 Dato-DXd 或 AVANZAR 的研究肯定已經很快註冊，以便在 2025 年進行讀數。這就是您所肯定的，您會根據該研究提交文件嗎？我知道它的設計與 TL07 和 08 有所不同？然後，在 DESTINY-Breast06 的 HER2 上，納入超低族群會在多大程度上擴大可尋址患者群體？我想您之前曾說過，大約 50% 的乳癌是由於 HER2 水平低所致。 HER2超低值會增加多少？

Susan?

蘇珊？

Yes. So for AVANZAR -- Michel, do you have it? Yes, accrual has gone very well, which just I think demonstrates the interest and the potential, not just of data Dato-DXd, but the combination in particular with Dato-DXd plus immune checkpoint inhibition. As you know, we've seen exciting data in a couple of different settings from the TROPION-Lung02 and 04 data sets as well as the BEGONIA study in triple-negative breast cancer. I think investigators are very interested in that the potential that this has to further improve the outcomes for patients with first-line non-small cell lung cancer.

是的。 AVANZAR－米歇爾，你有嗎？是的，應計進展非常順利，我認為這表明了人們的興趣和潛力，不僅是數據 Dato-DXd，而且特別是與 Dato-DXd 加上免疫檢查點抑制的組合。如您所知，我們從 TROPION-Lung02 和 04 資料集以及三陰性乳癌 BEGONIA 研究中的幾個不同設定中看到了令人興奮的數據。我認為研究人員對此非常感興趣，因為這有可能進一步改善第一線非小細胞肺癌患者的治療結果。

The study is progressing very quickly in recruitment, as you pointed out. The second 1 is DB06 and the low maybe for you, Dave?

正如您所指出的，這項研究在招募方面進展非常快。第二個 1 是 DB06，低也許適合你，戴夫？

Yes. So Thanks, Emily, for the question on that. So I think as we -- 2 things that I think are important about DB06. The first 1 is, is that it expands the opportunity if it's positive, like you highlighted to move into the ultra low specifically on that question, just to lay this out. So if we look at hormone receptor positive metastatic breast cancer, within the 60% are the IHC 1+ and 2+. So that's the HER2 low that's covered by DB04. Then we've got 25% that we estimate that's in this 0 to 1 category. So that's how much it adds within this. And then you've got about 15% that are the true zeros.

是的。謝謝艾米麗提出這個問題。所以我認為，對於 DB06，我認為有兩件事很重要。第一個是，如果它是積極的，它會擴大機會，就像你強調的那樣，專門針對這個問題進入超低水平，只是為了說明這一點。因此，如果我們觀察到荷爾蒙受體陽性轉移性乳癌，60% 的患者 IHC 為 1+ 和 2+。這就是 DB04 涵蓋的 HER2 低點。那我們估計有 25% 屬於這個 0 到 1 類。這就是它在其中添加的內容。然後大約有 15% 是真正的零。

So first is that expansion outside of the 1+s into the ultra lows, and then also it's moving a line earlier. And so by moving the line earlier, there's 2 opportunities to see growth, and it will be data dependent, but 1 of those is, of course, a longer duration of therapy you'd hope to get as you move earlier.

因此，首先是從 1+ 之外擴展到超低點，然後它也在更早地移動一條線。因此，透過提前移動生產線，有兩個機會看到成長，這將取決於數據，但其中之一當然是，當您提前移動時，您希望獲得更長的治療持續時間。

The other is, is that if the data are really compelling, you could see that, that puts some pressure on what we see as a lot of endocrine recycling that takes place within these patients. So again, that will be data dependent. We'll have to see what the magnitude of benefit is. But there's 3 different opportunities for 06 to contribute to growth moving forward.

另一個是，如果數據確實令人信服，你可以看到，這會對我們所看到的這些患者體內發生的大量內分泌循環帶來一些壓力。再說一遍，這將取決於數據。我們必須看看好處有多大。但 06 有 3 個不同的機會為未來的成長做出貢獻。

It's Matthew Weston from UBS. 2 Questions. And if the first 1 I can stick with in HER2 as well. I think 4Q U.S. sales probably were a little bit light in terms of growth of what people were expecting when Daiichi reported them. So total end-user sales. And at the time, I think Daiichi commented that penetration was reaching plateau in some of the U.S. markets, but with the data expansion coming, there was going to be much more opportunity. .

我是瑞銀集團的馬修‧韋斯頓。 2 個問題。如果第一個我也可以在 HER2 中堅持使用。我認為，就第一季報告時人們的預期成長而言，美國第四季的銷售額可能有點低。最終用戶銷售總額。當時，我認為 Daiichi 評論說，美國一些市場的滲透率已達到穩定水平，但隨著數據擴展的到來，將會有更多的機會。 。

I think a lot of investors felt that HER2 low was significantly bigger than suggesting it [already] plateaued. So I'd love to understand what's happening there. But also, Dave, if you can touch on HER2 PAM tumor. It seems to fly under the radar, may will actually be quite a significant indication.

我認為很多投資者都認為 HER2 低點明顯高於其[已經]趨於穩定的水平。所以我很想了解那裡發生了什麼事。而且，Dave，您能否談談 HER2 PAM 腫瘤。它似乎在雷達下飛行，實際上可能是一個相當重要的跡象。

And then if I rather on the second question, you added into guidance that there's essentially pointing to a onetime asset sale being something to take into account for 2024. I don't remember you're doing that for quite some time, suggesting it might be of a significant size. Is there any way you can help frame it?

然後，如果我更願意回答第二個問題，您在指導中補充說，基本上指出一次性資產出售是2024 年需要考慮的事情。我不記得您這樣做已經有一段時間了，這表明它可能會具有很大的規模。有什麼辦法可以幫助框起來嗎？

You want to start?

你想開始嗎？

Matthew, on in HER2, and I made this comment in my prepared remarks, and I think that it's an important piece, which is I had been commenting in quarters past that we had found, that we had hit a 50% really kind of threshold that we were running into in both HER2-positive and HER2 low. But that we knew that there was opportunity to drive continued growth beyond that. And I was really pleased to see, and we've been really pleased to see that we've been putting more effort against our promotional efforts within the U.S. and large markets within Europe.

馬修，在HER2 中，我在準備好的發言中發表了這一評論，我認為這是一篇重要的文章，我在過去的幾個季度中一直在評論我們發現，我們已經達到了50%的真正閾值我們在 HER2 陽性和 HER2 低的情況下都遇到了這種情況。但我們知道，除此之外還有機會推動持續成長。我真的很高興看到，我們真的很高興看到我們在美國和歐洲大型市場的促銷工作上投入了更多的努力。

We've done that in conjunction with the Truqap launch to really make sure that we've got the promotional muscle that we need out there, and we're seeing movement in the HER2-positive new patient starts. And so that's moving in the right direction and going the right level. Now if you think about where we were, basically, Matthew, what I think happened was we had replaced a lot, if not almost all of the Kadcyla use.

我們在 Truqap 推出的同時做到了這一點，以真正確保我們擁有所需的宣傳力量，並且我們看到 HER2 陽性新患者開始出現變化。因此，這正在朝著正確的方向前進，並達到正確的水平。現在，如果你想想我們的情況，基本上，馬修，我認為發生的事情是我們已經更換了很多（如果不是幾乎全部）Kadcyla 使用。

And now we're moving into some harder yards, but we're getting traction against it. We turn to HER2 low, HER2-low is again an opportunity for continued growth beyond where we've gotten to. It is, in many respects, a more complicated discussion to be able to have because we're talking about multiple therapeutic alternatives that exist within the hormone receptor positive space. We're obviously working on testing efforts.

現在我們正在進入一些更困難的場地，但我們正在獲得阻力。我們轉向 HER2 low，HER2-low 再次成為我們持續成長的機會。從許多方面來看，這是一個更複雜的討論，因為我們正在討論存在於荷爾蒙受體正空間內的多種治療替代方案。顯然我們正在努力進行測試。

All of this, though, I think that again, I've got optimism that we've got an opportunity to continue to grow. I think that in HER2 has a lot of growth in front of it with 03 and 04 still in the U.S., still in Europe, and I think that 06, which Emily just asked about, would be further tailwinds to add to that.

儘管如此，我再次認為，我對我們有機會繼續發展持樂觀態度。我認為 HER2 前面還有很多增長，03 和 04 仍然在美國，仍然在歐洲，而且我認為 Emily 剛剛問到的 06 將是進一步的推動力。

PAM tumor?

PAM腫瘤？

PAM tumor. PAM tumor is a spot where right now, we've got breakthrough therapy designation in later lines in the highest of over expressors. And so I think that when you take a look at that population, you've got several thousands of patients across multiple tumor types that could be addressable for this. And while our early label might be relatively modest compared to, for example, the 03 and 04 opportunities. I think that the more evidence generation that takes place, the more that we continue to do work in this space. And if we can demonstrate in the lower levels of expression, I think PAM tumor is exactly that third leg of the stool that Susan and I were talking about to add to HER2-positive breast and HER2 low to be a good growth driver in the midterm for in HER2.

PAM 腫瘤。 PAM 腫瘤是目前我們在最高過度表現者的後續系列中獲得突破性治療指定的地方。所以我認為，當你觀察這個族群時，你會發現數千名跨多種腫瘤類型的患者可以解決這個問題。雖然我們早期的標籤可能相對溫和，例如與 03 和 04 的機會相比。我認為產生的證據越多，我們在這個領域繼續做的工作就越多。如果我們能夠證明較低的表達水平，我認為 PAM 腫瘤正是 Susan 和我正在討論的第三條腿，將其添加到 HER2 陽性乳房和 HER2 低水平中，成為中期良好的生長驅動力對於HER2 來說。

So before Aradhana, do you want to take up...

所以在 Aradhana 之前，你想接受...

Yes, Matthew. So we talked about the other income, which we expect to decline substantially. And again, last year, remember, there were 2 particular transactions that contributed a large amount. So we've not signaled any asset sales. We do expect collaboration revenue to increase substantially. And we've talked about milestones and potential transactions we're contemplating, but we're not in a position to give more details today, and we'll see how the year unfolds.

是的，馬修。所以我們談到了其他收入，我們預計會大幅下降。再說一次，請記住，去年有兩筆特定交易貢獻了大量資金。所以我們還沒有發出任何資產出售的訊號。我們確實預期協作收入將大幅增加。我們已經討論了我們正在考慮的里程碑和潛在交易，但我們今天無法提供更多細節，我們將看看這一年的進展。

Pascal, super briefly, 1 thing that I forgot to mention on this. NCCN guidelines have included now endometrial, cervical and ovarian for and HER2 within the population that we got the priority review for. So I do think that, that's an acknowledgment that the clinical community is seeing the benefit of that study.

帕斯卡，非常簡單，我忘了提到這一點。 NCCN 指南現已將子宮內膜、子宮頸和卵巢以及 HER2 納入我們優先審查的人群中。所以我確實認為，這是對臨床界正在看到這項研究的好處的認可。

It's Andrew Baum with Citi. Staying with in HER2. And PAM tumor trial. So you have HER2 low as part of that trial, and there's been very clear signals and many malignancies that HER2 is active.

我是花旗銀行的安德魯·鮑姆。留在 HER2 中。以及PAM腫瘤試驗。因此，作為該試驗的一部分，HER2 較低，並且有非常明顯的信號和許多惡性腫瘤表明 HER2 處於活躍狀態。

And obviously, you have the manufacturing, it's been derisked. So my question is, are you leaving money on the table by not seeking to expedite development for individual HER2 low indications because it looks like you're not going to get approval for PAM tumor in HER2 low? So you're going to need to set trials. There are competitors with HER2 assets, we've initiated trials in those HER2-low settings. So have you just left white space for a competitor to come in when you've got an asset that you could be monetizing in that setting?

顯然，你擁有製造能力，它已經消除了風險。所以我的問題是，由於看起來您不會獲得針對 HER2 低的 PAM 腫瘤的批准，因此您不尋求加快個別 HER2 低適應症的開發，是否會浪費金錢？所以你需要設定試驗。有些競爭對手擁有 HER2 資產，我們已經在 HER2 低的環境中啟動了試驗。那麼，當您擁有可以在這種情況下貨幣化的資產時，您是否只是為競爭對手的介入留下了空白？

And then the second question is in relation to Truqap. I'm curious what you think of the enabolosib data? And how that's going to impact the use of Truqap, given you're hitting the same PI3K-AKT pathway?

第二個問題與 Truqap 有關。我很好奇您對 enabolosib 數據有何看法？鑑於您正在使用相同的 PI3K-AKT 途徑，這將如何影響 Truqap 的使用？

Susan?

蘇珊？

Yes. So for the white space question, when you got a brand like in HER2, which has really exceptional activity across. I think the philosophy is to make sure that we develop it to the maximum of its potential. So again, not everything that we're planning to do is currently visible, but you'd expect to see other trials. So I do think that we can build on what we've actually seen with PAM tumor, and I think it creates a lot of opportunity there. So we intend to leave this little white space as possible.

是的。因此，對於空白問題，當您擁有像 HER2 這樣的品牌時，它的活動確實非常出色。我認為我們的理念是確保我們最大限度地發揮它的潛力。再說一遍，目前我們計劃做的並不是所有事情都是可見的，但您預計會看到其他試驗。因此，我確實認為我們可以在 PAM 腫瘤的實際觀察基礎上進行研究，我認為這創造了許多機會。所以我們打算盡可能地留下這個小空白。

And in terms of the...

就...而言

You want to address the market size for this.

您想要解決這個問題的市場規模。

Yes, sure. I mean look, I think that what I would comment on most, Andrew, is that we're seeing very positive receptivity to Truqap. We've seen strong uptake in terms of number of new patients that are being started on therapy. We're actually hearing an awful lot of desire among the community to have seen a broader label based upon the data sets that were presented and what we've seen. And obviously, within the context of the competitive landscape, the Truqap data will ultimately be looked at within that context, but I think it really is showing favorably within that context. And we anticipate that we'll continue to have a strong launch for the medicine through the year and look forward to the additional life cycle readouts that we're going to have on the heels of, obviously, the 291.

是的，當然。我的意思是，安德魯，我想我最想評論的是，我們看到了對 Truqap 非常積極的接受度。我們看到開始接受治療的新患者數量強勁。實際上，我們聽到社區中非常強烈的願望，希望根據所提供的數據集和我們所看到的內容看到更廣泛的標籤。顯然，在競爭格局的背景下，Truqap 數據最終將在這種背景下進行研究，但我認為它確實在這種背景下表現出了有利的表現。我們預計，今年我們將繼續大力推出該藥物，並期待在 291 之後我們將獲得更多的生命週期讀數。

So again, there are other opportunities, I would just say with capivasertib for combination, but also remember that it treats a broader group of patients than just the PI3 kinase of a mutant group. You've got [P term] and you've got the AKT activation as well. So there's multiple ways in which it is different. But I think that the first-line space is also something that is of interest.

所以再說一遍，還有其他機會，我只想說與 capivasertib 進行組合，但也要記住，它治療的患者群體更廣泛，而不僅僅是突變組的 PI3 激酶。您已經獲得了 [P 術語]，並且還獲得了 AKT 激活。因此，它有多種不同之處。但我認為一線空間也是令人感興趣的東西。

Andrew, I mean, I think that the pace on this and maybe I skipped over because I thought it was kind of without saying, but Truqap is post CDK4/6 and the [invos] is not. So we are looking at different populations and different spots.

Andrew，我的意思是，我認為這方面的節奏，也許我跳過了，因為我認為這是不言而喻的，但 Truqap 是 CDK4/6 後的版本，而 [invos] 不是。所以我們正在研究不同的人群和不同的地點。

It is a different population. So they're taking into that first-line setting, fast progresses. So it's not -- even if you take the same population that went into 291 and look at them in the first line, they don't completely overlap with the [anabolism] patient population. I hope that's clear.

這是一個不同的人群。所以他們正在進入第一線，進展很快。所以事實並非如此——即使你選取進入 291 的相同人群並在第一行查看它們，它們也不會與[合成代謝]患者人群完全重疊。我希望這是清楚的。

It's Peter Welford with Jefferies. Two questions sticking to the norm. So first question is on the investor event on the 21st of May. I think it was called after it's an R&D event. I guess curious, can you outline, is this going to be a event very much focused on the midterm pipeline? Or will you also be giving that 10-year vision?

我是彼得·韋爾福德和傑弗里斯。有兩個問題符合規範。第一個問題是關於 5 月 21 日的投資者活動。我認為這是在研發活動之後命名的。我想很好奇，您能概述一下，這將是一個非常關注中期管道的活動嗎？或者您也會給出十年願景嗎？

And on that, is this going to be a 10-year vision setting another 10-year revenue aim? And I guess, what sort of granularity should we anticipate when we look forward to how you're going to set the aim for the next period?

就此而言，這是否會成為設定另一個 10 年收入目標的 10 年願景？我想，當我們期待您將如何設定下一個時期的目標時，我們應該預期什麼樣的粒度？

And then the second one is on Airsupra. So you mentioned obviously that the 2023 was very much a year of building access, building awareness, building this. I guess curious now in 2024, you -- the comment made, I think, was over time, we expect U.S. PCPs to change 50 years of habit. I mean that sounds there's still a lot of slog to go. So you just talk about how [the paid] discussions gone? Was that successful? Is the barrier now the doctors? Or should 2024 be a year where we got anything in the model? Or is this another year where we should be really thinking about the inflections yet to come?

第二個是 Airsupra。所以你顯然提到，2023 年很大程度上是建立准入、建立意識、建立這一點的一年。我想現在很好奇，在 2024 年，您所做的評論，我認為，隨著時間的推移，我們預計美國 PCP 會改變 50 年的習慣。我的意思是，聽起來還有很多困難要做。所以你只是談論[付費]討論怎麼樣了？那成功了嗎？現在的障礙是醫生嗎？或者說 2024 年我們應該在模型中得到任何東西？或者說，今年是我們應該真正思考即將到來的變化的一年嗎？

So 2 great questions, Peter. Let me just cover the first 1 and Ruud, you could cover Airsupra. So the R&D Day, really what we want to do, as I explained earlier is, explained what our strategy is and why we think we can grow strongly over the next 10 years.

這是兩個很好的問題，彼得。讓我只介紹第一個 1 和 Ruud，你可以介紹 Airsupra。因此，正如我之前解釋的那樣，研發日實際上是我們想要做的事情，解釋了我們的策略是什麼以及為什麼我們認為我們可以在未來 10 年強勁成長。

So we are, of course, going to look at our midterm pipeline, but also we want to look at the investments we're making in new technologies, new platforms, that will actually deliver growth from '28, '29 and beyond. So we actually give you a good understanding of not only the near term but also the midterm and the long term. As it relates to whether we're going to set up a long-term revenue ambition we may, but we haven't decided this.

因此，我們當然會關注我們的中期管道，但我們也想關注我們在新技術、新平台方面的投資，這些投資實際上將在 28 年、29 年及以後帶來成長。因此，我們實際上不僅讓您對近期，而且對中期和長期都有很好的了解。因為這關係到我們是否要訂定長期的收入目標，我們可能會這樣做，但我們還沒有決定。

But I can tell you that we are very, very confident that we can actually grow very strongly over the next few years and work through some of the issues that have been mentioned by some, for instance, Medicare (inaudible) reform, we can work through that. In the end, the impact of this is there, but it's relatively limited. I hesitate to use the word marginal, but it's quite limited in the context of our global sales. So we can walk through this. We can walk through the patent expiries that we have that are limited and continue to deliver very strong growth.

但我可以告訴你，我們非常非常有信心，我們實際上可以在未來幾年內實現非常強勁的成長，並解決一些人提到的一些問題，例如醫療保險（聽不清楚）改革，我們可以努力解決透過那。歸根結底，這個影響是有的，但相對有限。我不太願意使用「邊際」這個詞，但在我們的全球銷售背景下，這個詞相當有限。所以我們可以逐步了解這一點。我們可以度過有限的專利到期，並繼續實現非常強勁的成長。

And of course, it's not going to be the same gross number every year. But if you look at it over the next 5 years and then 10 years, we certainly can grow, and that's what we actually want to hopefully convince you as we share our strategy and we'll see whether we come up with a number or not. Go on.

當然，每年的總數量不會相同。但如果你看看未來 5 年和 10 年，我們當然可以成長，這就是我們真正想要說服你的，因為我們分享我們的策略，我們將看看我們是否能提出一個數字。繼續。

Yes. Let me first rearticulate, let's say, the excitement we have regarding Airsupra. First of all, this is a very substantial market. Its in the United States alone, there are roughly 15 million to 18 million scripts only for submitral in the asthma 18 plus indication. Having said that, we started our journeys in order to gain access last year. So the good news is, we have now formulary listings in 3 of the largest commercial PBMs. Based on the registration, we were just too late in order to get Part D. So we are bidding for Part D in the course of 2024. So hopefully, that will create more access moving forward. Many patients anyway are in commercial are younger patients. What we have seen in the first few weeks, it's still very early days, is a very nice number of trialists already thousands of GPs, but also specialists are prescribing as Airsupra.

是的。讓我先重申一下我們對 Airsupra 的興奮之情。首先，這是一個非常龐大的市場。光是在美國，就有大約 1500 萬至 1800 萬份僅用於 18 歲以上氣喘適應症的藥物提交。話雖如此，我們去年就開始了獲得訪問權限的旅程。好消息是，我們現在已在 3 個最大的商業 PBM 中進行了處方清單。根據註冊情況，我們來得太晚了，無法獲得 D 部分。因此，我們將在 2024 年競標 D 部分。因此，希望這將創造更多的機會。無論如何，商業中的許多患者都是年輕患者。我們在最初幾週看到的情況還處於早期階段，試驗者數量非常多，已經有數千名全科醫生，專家們也開出 Airsupra 的處方。

Having said that, access is still, let's say, an issue we are working through. So we need to buy down the course, the scripts, the course per scripts quite substantially. So my clear stay is we are off of a very strong start in the United States. But equally, of course, it will take time to get enough access in order to switch off the now conversion and hence, then the sales will follow. And it's more or less the pattern we have seen with Breztri. You've seen in the announcement, Breztri is growing over 70%. It's on its way to become a blockbuster hopefully very soon. And I think we are expecting the same pattern also for Airsupra moving forward.

話雖如此，可以說，訪問仍然是我們正在解決的問題。因此，我們需要大量購買課程、腳本、每個腳本的課程。因此，我的明確看法是，我們在美國有一個非常強勁的開局。但同樣，當然，需要時間才能獲得足夠的訪問權限才能關閉當前的轉換，因此銷售才會隨之而來。這或多或少就是我們在 Breztri 身上看到的模式。您在公告中看到，Breztri 的成長率超過 70%。希望它很快就會成為轟動一時的作品。我認為我們預期 Airsupra 的未來也會出現同樣的模式。

I think really the important point, as Ruud said, is really to expect that this is not an oncology new indication that really addresses a big unmet need with a very fast sales ramp up. It's more progressive. But the beauty of this kind of inhaled products is that when you are established, you have a very durable asset. I mean look at Symbicort, it's been around for a long, long time. And it's still out there and it's still a very good product with good sales, very good profitability.

正如 Ruud 所說，我認為真正重要的一點是，真正期望這不是一個腫瘤學新適應症，能夠透過非常快速的銷售成長來真正解決巨大的未滿足需求。這是更進步的。但這種吸入產品的美妙之處在於，當你建立起來時，你就擁有了非常持久的資產。我的意思是看看 Symbicort，它已經存在了很長很長時間了。它仍然存在，並且仍然是一個非常好的產品，銷量良好，盈利能力非常好。

So we have to have the resilience to get it to the right level, and then it will stay at a good level for a long time to come because there's not a huge amount of competition, and there is a clear unmet need there.

因此，我們必須有韌性，使其達到正確的水平，然後在未來很長一段時間內保持在良好的水平，因為競爭並不激烈，而且存在明顯的未滿足的需求。

It's Mark Purcell from Morgan Stanley. Two questions. The first one for Aradhana. I guess what some people have been concerned by this morning is the certain anticipated transactions part of your CR guidance, which you expect to increase substantially in 2024. I guess they're triangulate that with a Part 1 selected moving forward.

我是摩根士丹利的馬克‧珀塞爾。兩個問題。第一個是阿拉達納。我想今天早上有些人擔心的是CR 指導中的某些預期交易部分，您預計這些交易將在2024 年大幅增加。我想他們正在對這一問題進行三角測量，並選擇向前推進的第1部分。

And the last time you move forward with a PARP inhibitor, you had a 1.6 billion up from milestone from a partner. So can you confirm that R&D as a potential revenue is still in the low 20s, I presume it is. But more importantly, could you give us some qualitative guidance on SG&A, which obviously stepped up a lot in Q4 and just where that will land for the full year '24?

上次您推進 PARP 抑制劑時，您從合作夥伴處獲得了 16 億美元的里程碑資金。那麼您能否確認研發作為潛在收入仍處於 20 多歲以下，我認為是這樣。但更重要的是，您能否給我們一些有關 SG&A 的定性指導，該指導在第四季度明顯提高了很多，以及 24 年全年的具體情況如何？

And then the second question is on your TKM syndrome pipeline. I guess this is all about going after symptomatic diseases like obesity and [detection] heart failure to capture (inaudible) diseases like CKD.

第二個問題是關於您的 TKM 綜合症管道。我想這一切都是為了追蹤肥胖和[檢測]心臟衰竭等症狀性疾病，以捕捉（聽不清楚）慢性腎臟病等疾病。

So could you help us understand the opportunity here and the level of investment you're going to put behind this combination of assets, this franchise. And then specifically on the Eccogene drug. We're getting a lot of questions around manufacturing. If you can help us understand how many CMC steps this product has given that with (inaudible) is estimated to be over 30% and therefore, incredibly difficult to scale.

那麼您能否幫助我們了解這裡的機會以及您將在該資產組合、該特許經營權背後投入的投資水平。然後是專門針對 Eccogene 藥物。我們收到了很多有關製造的問題。如果您能幫助我們了解產品提供了多少 CMC 步驟（聽不清楚），估計會超過 30%，因此難以擴展。

Aradhana?

阿拉達納？

Sure. So on the SG&A front, if you look at fourth quarter last year, which I think you mentioned is a concern in terms of the step-up. If you look at the last several years, the fourth quarter is always 1 of our largest quarter in terms of SG&A. That does not mean that's the run rate sort of obviously going forward. And then when you look at 2023 and our updated guidance and some of these -- some of the tax transactions and net tax changes that we were -- we had in mind. And we manage the whole P&L. So we chose to invest in certain areas, including some of the launches that you heard about from Ruud and so forth.

當然。因此，在SG&A方面，如果你看看去年第四季度，我認為你提到的這是一個關於升級的問題。如果你看看過去幾年，第四季始終是我們 SG&A 最大的季度之一。這並不意味著運行率明顯向前推進。然後，當您查看 2023 年和我們更新的指南以及其中的一些內容（我們的一些稅收交易和淨稅收變化）時，我們就想到了。我們管理整個損益表。所以我們選擇投資某些領域，包括你從范尼那裡聽說的一些產品等等。

So that sort of explains the fourth quarter of 2023. I think on looking on 2024, we've obviously given guidance on top line and bottom line. I've talked about some of the increase you'll have in finance expenses. I've talked a little bit about the gross margin expectations. And so you can sort of consider that and see where the SG&A growth will be. We are obviously committed to operating leverage, and we do expect that given those puts and takes that the SG&A growth will be lower than the total revenue growth.

這可以解釋 2023 年第四季的情況。我認為展望 2024 年，我們顯然已經就營收和利潤給出了指導。我已經談到了財務費用的一些增加。我已經談過一些關於毛利率的預期。因此，您可以考慮這一點，看看 SG&A 的成長情況。我們顯然致力於營運槓桿，並且我們確實預計，考慮到這些看跌期權和期權，SG&A 成長將低於總收入成長。

Maybe Emmanuel just to add to this. I understand the question also the concern that you mentioned and connecting to James earlier questions. I think it's important to keep in mind that we believe the product sales -- in our guidance, product sales will grow strongly. I mean the guidance is low double digit to low teens, right? So that's a range.

也許伊曼紐爾只是為了補充這一點。我理解這個問題，也理解你提到的問題以及與詹姆斯之前的問題的連結。我認為重要的是要記住，我們相信產品銷售——在我們的指導下，產品銷售將強勁成長。我的意思是指引是低兩位數到低十幾歲，對吧？所以這是一個範圍。

And product sales will be in that range. So message is, our top line revenue growth is not driven. I mean it's not dependent on this one-off, as you said. Rudd?

產品銷售也將在這個範圍內。因此，我們傳達的訊息是，我們的營收成長並未受到推動。我的意思是，正如你所說，這並不依賴這一次性的事情。路德？

Yes. So let me first phrase that the opportunity in CKD market. There are more than 800 million patients around the world suffering from CKD. And despite the progress we have seen in the last few years, especially the SGLT2 class, including our on Farxiga, there's still a huge unmet medical need. And hence, our -- let's say, excitement also the products we have in development. Clearly, 1 is the combination of dapagliflozin placebo tenant. And of course, Sharon can talk about that as well, makes us quite bullish about this opportunity.

是的。首先我要說的是 CKD 市場的機會。全球有超過 8 億患者患有 CKD。儘管我們在過去幾年中取得了進步，特別是 SGLT2 級，包括我們的 Farxiga，但仍然存在巨大的未滿足的醫療需求。因此，我們對正在開發的產品也感到興奮。顯然，1是達格列淨安慰劑租戶的組合。當然，莎倫也可以談論這一點，這讓我們非常看好這個機會。

Now equally, Marc is developing a [Alexion] potential IgAN molecule. This is a space where many companies have left the field. So the kidney space, while we believe that there are huge opportunities based on our pipeline in order to really build a very strong pipeline. So I don't know whether you want to talk a little bit about 1 of the combinations, Sharon.

現在，Marc 正在開發一種 [Alexion] 潛在的 IgAN 分子。這是許多公司已經退出的領域。因此，腎臟空間，雖然我們相信基於我們的管道存在巨大的機會，以便真正建立一個非常強大的管道。所以我不知道你是否想談談其中一種組合，莎倫。

Sure, Rudd. So you asked us about the scope of our investment, and then I'll also address your question about our space, our focus on metabolism. So to reframe what Ruud said, there are 20 million people living with CKD and hypertension in the U.S. alone. So clearly, this is a very large market, and it speaks to the interrelatedness of cardio renal and cardiometabolic disease. So thinking about how we can address the different flavors of CKD with our portfolio. We are advancing the baxtro Dato combination. It's in Phase III for CKD. We have Boston Renan combined with dapagliflozin, the miracle Phase II study in CKD with heart failure achieved high-level results at the end of last year.

當然，路德。所以你問了我們投資的範圍，然後我也會回答你關於我們的空間、我們對新陳代謝的關注的問題。因此，根據 Ruud 的說法，光在美國就有 2000 萬人患有 CKD 和高血壓。顯然，這是一個非常大的市場，它說明了心臟和腎臟疾病和心臟代謝疾病的相互關聯性。因此，請思考如何透過我們的產品組合來應對不同類型的 CKD。我們正在推進 baxtro Dato 組合。目前正處於 CKD 的第三階段。我們在去年年底波士頓瑞南聯合達格列淨治療慢性腎臟病心臟衰竭的奇蹟二期研究取得了高水準的結果。

And we really look forward to sharing those at an upcoming conference, and we are in the deck of Phase III planning at this point. And then the combination of zibotentan, with dapagliflozin allows us to address CKD with high proteinuria, and we have initiated the ZENITH Phase III trial. So clearly, we're heavily invested in this space, and we view this as an opportunity to manage the complexity of cardiorenal disease and to help people manage their overall health.

我們真的很期待在即將舉行的會議上分享這些內容，目前我們正在製定第三階段的計畫。然後，zibotentan 與 dapagliflozin 的組合使我們能夠解決高蛋白尿的 CKD，並且我們已經啟動了 ZENITH III 期試驗。顯然，我們在這個領域投入了大量資金，我們認為這是一個管理心腎疾病複雜性並幫助人們管理整體健康的機會。

With that in mind, we do think that our metabolism portfolio dovetails very nicely with these efforts to achieve organ protection while managing health because we understand that these diseases are highly interconnected.

考慮到這一點，我們確實認為我們的新陳代謝組合與這些在管理健康的同時實現器官保護的努力非常吻合，因為我們知道這些疾病是高度相互關聯的。

So if we think that there are 64 million people with heart failure worldwide, 15 million alone in Europe -- in Europe alone. And we know that 50% of those patients have renal impairment and 42% have some interrelated metabolic disease. It makes sense that we want to continue to expand our portfolio in the metabolism space. We have been, I think, very open about the acquisition and our interest in the 5004 program. Also this is not our only program. This is 1 piece of our overall focus on metabolic disease.

因此，如果我們認為全世界有 6400 萬人患有心臟衰竭，其中僅歐洲就有 1500 萬人——僅在歐洲。我們知道，其中 50% 的患者患有腎功能損害，42% 的患者患有一些相關的代謝疾病。我們希望繼續擴大我們在新陳代謝領域的產品組合，這是有道理的。我認為，我們對於此次收購以及我們對 5004 計劃的興趣一直非常開放。而且這不是我們唯一的計劃。這是我們對代謝疾病的整體關注的一部分。

Moving along at pace. We also have a long-acting amylin as well as a GLP-1 glucagon dual agonist. Speaking briefly to 5004, we are excited about this asset. We are encouraged to see it move forward into 2 Phase IIb trials this year.

沿著步伐前進。我們還有長效型胰島澱粉樣多勝肽和 GLP-1 胰高血糖素雙重激動劑。簡單談談 5004，我們對這項資產感到興奮。我們很高興看到它今年進入 2 項 IIb 期試驗。

You want to say a few words about the manufacturing steps.

您想談談製造步驟。

Actually, I'll say 2 things. The first is that, 1 key focus for 5004 is being able to simplify our manufacturing process and come up with a simpler synthetic route. And together with our collaborators at Eccogene, I think we're making substantial progress on that front. The second thing that I will say continues to speak to the interconnectedness of disease, which is that 5004 as an orally bioavailable molecule is very well suited to potential combinations with other oral molecules in our portfolio. And so I would include in that list, Farxiga as well as our oral PCSK9 inhibitor.

其實我想說兩點。首先，5004 的一個重點是能夠簡化我們的製造流程並提出更簡單的合成路線。我認為我們與 Eccogene 的合作者一起在這方面取得了實質進展。我要說的第二件事繼續談到疾病的相互關聯性，即 5004 作為一種口服生物利用分子非常適合與我們產品組合中其他口服分子的潛在組合。因此，我將 Farxiga 以及我們的口服 PCSK9 抑制劑納入該清單。

And so we look forward to sharing results of our Phase I trial, which only recently wrapped up. This was a highly controlled 4-week inpatient trial that was piloted by Eccogen. We achieved database lock at the end of December, and we look forward to sharing the data at an upcoming medical conference.

因此，我們期待分享最近剛結束的第一階段試驗的結果。這是一項由 Eccogen 主導的高度對照的為期 4 週的住院試驗。我們在 12 月底實現了資料庫鎖定，我們期待在即將召開的醫學會議上共享資料。

Maybe 1 quick point is that every focuses on obesity, because there is this big segment of people are not [obesed] their overweight. So they don't need to lose 25% weight. They need to lose a bit of weight and they have metabolic disease sometimes with organ damage as well. And in that segment, which is extremely large and where the payers are more likely to pay managing the various dimensions of the metabolic syndrome with the PCSK9 with Dato, with baxdrostat and being able to combine is going to be a substantial advantage if you have this portfolio that we have in.

也許有一個要點是，每個人都關注肥胖，因為有很大一部分人的體重並未[肥胖]。所以他們不需要減掉25%的體重。他們需要減輕一些體重，而且他們患有代謝疾病，有時還伴隨器官損傷。在這個非常大的細分市場中，付款人更有可能支付與 Dato 的 PCSK9 和 baxdrostat 來管理代謝症候群的各個方面的費用，並且如果您擁有以下功能，那麼能夠結合起來將是一個巨大的優勢我們擁有的投資組合。

Simon Baker from Redburn Atlantic. Two for me, please. Firstly, on Tezspire and Saphnelo. Now they've both been on the market for a while. I wonder if you could give us an update on the characteristics of the prescribers and patients so far for both drugs? Question on Gracell and FasTCAR. If you could just give us an idea of how easily scalable that manufacturing technology is?

雷德本大西洋公司的西蒙貝克。請給我兩個。首先是 Tezspire 和 Saphnelo。現在它們都已上市一段時間了。我想知道您能否向我們介紹迄今為止這兩種藥物的處方者和患者特徵的最新情況？關於 Gracell 和 FasTCAR 的問題。您能否讓我們了解一下該製造技術的可擴充性如何？

And also, a bit more color on the comment that Gracell have made in the past that there was a substantial manufacturing cost advantage here, which sounds like it could be quite significant as you move into autoimmune areas. Any color on that would be very much appreciated.

此外，Gracell 過去發表的評論也有更多色彩，即這裡具有巨大的製造成本優勢，這聽起來當你進入自體免疫領域時可能會非常重要。任何顏色都將非常感激。

Yes. Let me first start with your question about Tezspire. The product is doing very well, not only in the United States but also equally in the markets we have just launched. We have leading NBRx, or new-to-brand market shares in countries like Spain and Germany. The patient population is a very interesting one. It's primarily the patients who have, let's say, a moderate or normal is in the full count but are allergic. So the low T2 patient population is highly dominant in what we see so far. But equally, we also know from our clinical studies that Tezspire0 is also very well established in the highest in the fills in the United States. So the broad utility of the products and no need for a biomarker, no need for phenotyping, makes it a highly attractive choice for especially allergies and more and more pulmonologists as well.

是的。讓我先回答你關於 Tezspire 的問題。該產品不僅在美國，而且在我們剛推出的市場上表現都非常好。我們在西班牙和德國等國家擁有領先的 NBRx 或新品牌市場份額。患者群體是一個非常有趣的群體。主要是那些患有中度或正常過敏但過敏的患者。因此，到目前為止，低 T2 患者群體在我們所看到的情況中占主導地位。但同樣，我們也從我們的臨床研究中得知，Tezspire0 在美國的填充率中也處於領先地位。因此，該產品的廣泛實用性以及不需要生物標記、不需要表型分析，使其成為特別是過敏症患者和越來越多的肺科醫生的極具吸引力的選擇。

So we have high expectations and together with our partner MG and I think it's fair to say that the product is on its way to become a blockbuster anytime soon. So that's one. Saphnelo is another very nice story. It's the only interferon receptor antagonist. It has blown our lupus is a disease with multiple manifestations and multiple organ manifestations. It's particularly very impactful on skin disease, and we have seen very, very strong feedback from rheumatologists that patients primarily with skin manifestations are reacting very well on Saphnelo. Equally, only operating in the [inter veneous] markets as we speak.

因此，我們與我們的合作夥伴 MG 抱有很高的期望，我認為可以公平地說，該產品很快就會成為一款重磅產品。這就是其中之一。 Saphnelo 是另一個非常好的故事。它是唯一的干擾素受體拮抗劑。吹響了我們狼瘡是一種多表現、多重器官表現的疾病。它對皮膚疾病的影響特別大，我們已經看到風濕病專家非常非常強烈的回饋，主要有皮膚症狀的患者對 Saphnelo 反應非常好。同樣，正如我們所說，僅在[靜脈]市場中運作。

So we are doing for the last 1.5, 2 years, relatively large study for subcutaneous formulation. And I truly believe, hopefully next year, that study will read out, and we have a positive readout as we'll provide another clear opportunity. And as Sharon mentioned in her remarks, we are very keen to move Saphnelo also in multiple other indications in order to further grow the brand to also equally a blockbuster brands in the next few years.

因此，我們在過去的 1.5 年、2 年裡對皮下製劑進行了相對較大的研究。我堅信，希望明年這項研究將會公佈，我們將獲得積極的結果，因為我們將提供另一個明確的機會。正如 Sharon 在她的演講中提到的，我們非常熱衷於將 Saphnelo 轉移到多個其他適應症中，以便在未來幾年內進一步發展該品牌，使其成為同樣的重磅品牌。

Thanks, So Susan, do you want to comment on (inaudible)?

謝謝，蘇珊，您想發表評論嗎（聽不清楚）？

So as I mentioned in my prepared remarks. The actual time that you need to manufacture the [Fasco] is substantially shorter than for some other currently commercially available CAR-T therapies. That's 1 component of the turnaround time, obviously. So it's 1 component also of the manufacturing cost. I think it does help with scalability because the amount of time that you need to process each individual patient's batch is also shorter within the manufacturing facility. So what that means is that you do get increased capacity for a given size of the manufacturing building that you've created.

正如我在準備好的演講中所提到的。製造 [Fasco] 所需的實際時間比目前其他一些市售 CAR-T 療法要短得多。顯然，這是周轉時間的一部分。所以它也是製造成本的組成部分之一。我認為它確實有助於提高可擴展性，因為在製造工廠內處理每個患者批次所需的時間也更短。因此，這意味著對於您所創建的給定規模的製造建築，您確實獲得了更大的產能。

So that's important. But also, it means that you can be more predictable about the delivery. And because you are actually generating a smaller total number of the cells that have to be delivered to the patient the likelihood of success of each of those is higher. So all of these things, I think, contribute to the overall benefit that we see from the Fasco process.

所以這很重要。而且，這也意味著您可以更加可預測交付。而且，由於實際產生的需要輸送給患者的細胞總數較少，因此每種細胞成功的可能性較高。因此，我認為所有這些都有助於我們從 Fasco 流程中看到的整體效益。

Thanks, Susan. Maybe we could take 1 online question. Tim Anderson of Wolfe Research. Tim, over to you.

謝謝，蘇珊。也許我們可以回答 1 個線上問題。沃爾夫研究中心的蒂姆·安德森。提姆，交給你了。

Any headwinds to revenue growth for individual key brands in 2024 that you'd like to call out relative to where you see consensus. So in rare diseases, you're facing some new competition? In oncology, you talked about in HER2, but what about Tagrisso or Calquence. Calquence in the U.S. seems to be stalling out, for example? .

您想要指出的與您所看到的共識相關的各個關鍵品牌 2024 年收入成長的任何阻力。那麼在罕見疾病領域，您面臨一些新的競爭嗎？在腫瘤學方面，您在 HER2 中談到了，那麼 Tagrisso 或 Calquence 呢？例如，美國的 Calquence 似乎陷入了停滯？ 。

And then second question on Dato. Any risk to approval in the U.S. in lung and nonsquamous based on what you have today? To me, the regulatory precedents as it should be low risk, and you should get approved, but that's not necessarily the consensus view. So what's your confidence here? And what happens if OS misses and non-screamers remain supportive, but doesn't formally hit?

然後是關於拿督的第二個問題。根據您今天的情況，在美國批准用於肺部和非鱗狀細胞癌的藥物是否有風險？對我來說，監管先例應該是低風險的，你應該獲得批准，但這不一定是共識。那麼你對此有什麼信心呢？如果作業系統失誤並且非尖叫者仍然支持但沒有正式擊中，會發生什麼？

Tim, I'm going to propose Marc, you cover (inaudible) and the general competitive environment. Dave, you could cover Calquence and Tagrisso. And Tagrisso maybe also talk about not only the headwinds but also the potential upsides. And then Susan, you cover Dato.

提姆，我要推薦馬克，你負責（聽不清楚）和整體競爭環境。戴夫，你可以報道卡爾昆斯和塔格里索。泰格里索也許不僅談論了不利因素，還談論了潛在的好處。然後蘇珊，你負責報道拿督。

Yes.

是的。

So let me start with (inaudible). So basically, the headwind that we can anticipate is the introduction of biosimilars in the PNH indication. Two competitors have started to gain approval in 2023. The impact on '23 is still very limited, but obviously, this could increase over time. The way we counteract this headwind is by converting as fast as possible from Soliris to Ultomiris and in the main indications both neurology indication as well as PNH the conversion is very high. It's in the magnitude of 80%. That's the first thing.

讓我從（聽不清楚）開始。所以基本上，我們可以預見的阻力是在 PNH 適應症中引入生物相似藥。兩個競爭對手已開始在 2023 年獲得批准。對 '23 的影響仍然非常有限，但顯然，隨著時間的推移，這種影響可能會增加。我們應對這一不利因素的方法是盡快從 Soliris 轉換為 Ultomiris，並且在神經病學適應症和 PNH 的主要適應症中，轉換率非常高。其幅度為 80%。這是第一件事。

The -- where we're also sustaining the growth of the complement franchise is buying -- expanding our regional presence. And we have augmented significantly in 2023. We still have more work to do in '24. We are increasing the number of approval and reimbursement for Soliris as well as for Ultomiris.

我們也正在維持補充特許經營權的成長，即購買—擴大我們的區域業務。到 2023 年，我們的規模已顯著擴大。24 年我們還有更多工作要做。我們正在增加 Soliris 和 Ultomiris 的批准和報銷數量。

And lastly, this is a long-term work that we have been doing to make this franchise sustainable, we are continuing to develop new indications. We have anymore that has been approved recently in Europe and Japan with very rapid uptake. We are soon to get the U.S. approval, but we will also continue with other indications, which are presently in Phase III. So not only on the C5. And then we have also -- I forgot to buttify. We have the nobody bispecific 1720 givilimab that is well advanced in Phase III and should be coming to the market in (inaudible) very soon. So there is a future -- a very bright future for the C5 franchise and the complement franchise overall.

最後，這是我們為使該特許經營權可持續發展而一直在做的一項長期工作，我們正在繼續開發新的適應症。我們最近在歐洲和日本獲得了批准，而且應用非常迅速。我們很快就會獲得美國的批准，但我們也將繼續研究目前處於第三階段的其他適應症。所以不只在C5上。然後我們還有——我忘了​​反駁。我們擁有無人雙特異性 1720 givilimab，該藥物在 III 期試驗中進展順利，應該很快就會進入市場（聽不清楚）。因此，C5 特許經營權和整個補充特許經營權都有一個非常光明的未來。

Turning to oncology and Tim, on your question. So very directly on your first question, which is, are there any places where there's headwinds relative to consensus? I commented in my prepared remarks on the only 1 that I would call out, but I think it's important, which is that in Japan, in February, we had repricing on Imfinzi that I'm not sure is built into all of the models moving ahead, and we do anticipate because of some changes from weight-based to fixed dosing that we will see another in Japan, Imfinzi price adjustment.

關於你的問題，轉向腫瘤學和提姆。那麼，非常直接地回答你的第一個問題，即是否存在相對於共識而言有阻力的地方？我在準備好的評論中評論了我唯一要指出的一點，但我認為這很重要，那就是在日本，二月份，我們對Imfinzi 進行了重新定價，我不確定是否已將其內置於所有移動模型中未來，我們確實預計，由於從基於體重到固定劑量的一些變化，我們將在日本看到另一次 Imfinzi 價格調整。

With that said, on the specific question about Tagrisso. I'm enthusiastic about where Tagrisso ends the year and where it comes into next year. As I mentioned, we're seeing good underlying demand growth sequentially within the U.S. and within Europe. And I think that is coming on the heels of ADAURA and FLAURA performing well. We've got an opportunity in China despite the competition that we're seeing there to move out of this anticorruption shadow that I think has affected the ability to be able to really take advantage of a leadership position that we have, all doing the right thing, but just in terms of access in general to oncologists has been more limited.

話雖如此，關於 Tagrisso 的具體問題。我對 Tagrisso 的年末和明年的表現充滿熱情。正如我所提到的，我們看到美國和歐洲的潛在需求連續良好成長。我認為這是在 ADAURA 和 FLAURA 表現良好之後出現的。儘管我們看到那裡存在競爭，但我們在中國有機會擺脫反腐敗的陰影，我認為這影響了我們真正利用我們所擁有的領導地位的能力，一切都在做正確的事事情，但就一般而言，腫瘤學家的接觸機會更加有限。

We've got FLAURA2, which, knock on wood, we'll see an approval on here sometime within the year, we've got LAURA, which I think is a really important catalyst that will read out again here within the first half. So I look at the outset on this. And I think also on a competitive landscape basis, FLAURA2 positions us pretty nicely. On Calquence, no question that we've got a competitive environment, and we've got a direct competition. But I also like what our U.S. and European teams have been able to do in the face stack competition.

我們有 FLAURA2，敲敲木頭，我們將在今年的某個時候在這裡看到批准，我們有 LAURA，我認為這是一個非常重要的催化劑，將在上半年再次在這裡宣讀。所以我從一開始就看這個問題。我認為，從競爭格局的角度來看，FLAURA2 也為我們提供了相當不錯的定位。在卡爾昆斯，毫無疑問我們有一個競爭環境，而且我們有直接的競爭。但我也喜歡我們的美國和歐洲隊伍在面堆比賽中所取得的成績。

I think that within that, we've got a leadership position within frontline CLL that we've been able to maintain. I think if you take some of the months or the quarterly phasing out of the situation, we've seen really good, strong underlying demand growth on Calquence throughout the entirety of the year.

我認為，我們在 CLL 一線中保持了領導地位。我認為，如果你把某些月份或季度的情況逐步取消，我們會發現卡爾昆斯全年的潛在需求成長非常好、強勁。

I'm hopeful and optimistic that as co-pay within the U.S. is lowered. Pascal talked about this in his remarks, and we see affordability go from patients having to pay 5% of the catastrophic to 0, and therefore, a co-pay cap that is $2,000 that this is going to give patients the ability to be able to stay on and have greater adherence to continuous treatment to progression on BTK therapy.

我對美國自付費用的降低充滿希望和樂觀。帕斯卡在他的演講中談到了這一點，我們看到患者的負擔能力從必須支付 5% 的災難性費用變為 0，因此，共同支付上限為 2,000 美元，這將使患者有能力繼續堅持並更好地堅持連續治療直至BTK 治療出現進展。

So again, we have to see that play out. We have to see how that works through. But I think that these are elements that give me enthusiasm about the oncology portfolio and the opportunities in front of us.

所以，我們必須再次看到這結果。我們必須看看它是如何運作的。但我認為這些因素讓我對腫瘤學產品組合和眼前的機會充滿熱情。

I think this co-pay cap, it should really not be underestimated because if you look at the U.S. system on the Medicare side, it is going to be a very, very good system. I mean, many countries have co-pays. I mean Australia has co-pay, Switzerland had co-pay, many countries have co-pays. And here in the United States, people, patients are going to be able to say, "I'm not going to pay more than $2,000 a year, regardless of how many drugs are received, regardless of how much they cost $2,000".

我認為這個共同支付上限確實不應該被低估，因為如果你看看美國醫療保險方面的製度，這將是一個非常非常好的製度。我的意思是，許多國家都有自付額。我的意思是澳洲有自付費用，瑞士有自付費用，許多國家都有自付費用。在美國，人們、患者將能夠說，「我每年不會支付超過 2,000 美元，無論收到多少藥物，無論它們花費多少 2,000 美元」。

Now you might say $2,000 is a fair amount of money. But if you have a car insurance or house insurance, that's going to cost you at least that and many people can afford this.

現在你可能會說 2,000 美元是一筆相當可觀的錢。但如果你有汽車保險或房屋保險，那你至少要花這麼多錢，而且很多人都能負擔得起。

And it's a great level of reassurance in terms of taking your medicines and being adherent to them. And for us, it will mean a reduction of free goods, we have to give, which has been increasing substantially in the last few years as people -- more and more people cannot afford to cover the co-pays.

就服藥和堅持服藥而言，這是一個很大的保證。對我們來說，這將意味著我們必須提供的免費物品的減少，而在過去幾年裡，隨著人們——越來越多的人無法支付自付費用，免費物品一直在大幅增加。

It's Luisa Hector from Berenberg.

我是來自貝倫貝格的路易莎·赫克托。

Next question on Dato.

下一個問題是關於拿督的。

No, no, no. Sorry.

不不不。對不起。

So, can I answer? Okay. So first of all, thanks for the questions. We're confident that Dato-DXd is going to be important medicine in the treatment of non-small cell lung cancer. Obviously, we've been having ongoing discussions with the regulatory authorities. TL01 is a trial with a dual primary end point.

那麼，我可以回答嗎？好的。首先，感謝您提出的問題。我們相信 Dato-DXd 將成為治療非小細胞肺癌的重要藥物。顯然，我們一直在與監管機構進行持續的討論。 TL01 是一項具有雙重主要終點的試驗。

Obviously, we met PFS as one of those primaries, but OS is going to be important in the second to third line setting. When you think historically other than checkpoint inhibitors no medicines have demonstrated OS benefit and doses tax will currently remains the standard of care.

顯然，我們將 PFS 作為主要因素之一，但 OS 在第二到第三線設定中將很重要。從歷史上看，除了檢查點抑制劑之外，沒有任何藥物顯示出對 OS 的益處，且劑量稅目前仍將是護理標準。

I'll remind you that in the non-squamous population, the data that we presented at ASCO, we showed that the hazard ratio in the non-squamous for OS was 0.77 with a confidence interval that only just overlapped once. So it was 1.01 at the upper end.

我要提醒您的是，在非鱗狀細胞群體中，我們在 ASCO 上提供的數據表明，非鱗狀細胞群體中 OS 的風險比為 0.77，置信區間僅重疊一次。所以上限為 1.01。

So I think that shows that we're not just seeing a progression-free survival benefit, but there's a strong trend to OS within that patient population. So quite often as is normal as the OS events mature, we'll often have an update of the OS during a period of review, and we'd anticipate that during the period of review for TL01, we can update the OS.

因此，我認為這表明我們不僅看到了無惡化存活獲益，而且在該患者群體中存在強烈的 OS 趨勢。因此，隨著作業系統事件的成熟，我們經常在審查期間對作業系統進行更新，這是正常的，我們預計在 TL01 的審查期間，我們可以更新作業系統。

Luisa at Berenberg. I would like to ask is it correct to comment on the Icosavax deal and just the attractions of the assets there and the opportunity to enter the RSV market?

路易莎在貝倫貝格。我想問一下，僅評論 Icosavax 交易以及那裡資產的吸引力以及進入 RSV 市場的機會是否正確？

And then also maybe to pivot from that slightly bigger picture question. But essentially a margin question, sorry. You've shown us the fabulous pipeline progress, the breadth and depth. We see the entry into new therapeutic areas, the modalities, vaccines, DC T cell therapies, et cetera. So it's really bubbling. So really, it's about how you can be so confident in some margin expansion midterm. How can that happen? Is there a point where selling costs, the infrastructure stabilizes? How do these fabulous products compete for R&D budget? Is it about strict almost attrition, making sure absolutely the best projects are moving forward? So just any color on that so that you can give us confidence in the ability to raise margins given all the excitement within the pipeline?

然後也許還可以從那個稍微大一點的問題出發。但本質上是保證金問題，抱歉。你們向我們展示了令人驚嘆的管道進展、廣度和深度。我們看到新的治療領域、治療方式、疫苗、DC T 細胞療法等的進入。所以它真的很冒泡。所以實際上，這是關於如何對中期利潤擴張充滿信心的。怎麼會這樣呢？銷售成本和基礎建設是否有穩定點？這些出色的產品如何爭取研發預算？是關於嚴格的幾乎消耗，確保絕對最好的專案正在推進嗎？那麼，考慮到管道中的所有令人興奮的情況，只要有任何顏色，這樣您就可以讓我們對提高利潤的能力充滿信心嗎？

Thanks Lisa, for the question, for your interest. So the proposed acquisition of Icosavax really strenghthened our lead stage pipeline in vaccine and immune therapies. Because the Icosavax lead asset is the combination RSV and PV vaccine. That is Phase III ready.

謝謝麗莎提出這個問題，謝謝你的興趣。因此，擬議收購 Icosavax 確實加強了我們在疫苗和免疫療法方面的領先階段管道。因為 Icosavax 的主導資產是 RSV 和 PV 疫苗的組合。第三階段已經準備好了。

And that is important to us for 2 different perspective and one side, this is a next-generation vaccine technology within the respiratory vaccines because it's a protein virus like particle vaccine and importance of that vaccine is that they have a potential to be better, more effective and more safe than a non-VLP vaccine.

從兩個不同的角度和一方面來說，這對我們來說很重要，這是呼吸道疫苗中的下一代疫苗技術，因為它是一種類似顆粒疫苗的蛋白質病毒，該疫苗的重要性在於它們有可能變得更好、更多比非 VLP 疫苗更有效且更安全。

So basically, what you can expect to see from those vaccine is to have a higher efficacy and a longer durability of the fact and, at the same time, better safety profile. The second important aspect of this is that this is a combination of RSV and HMPV vaccine. And although there are a number -- you can argue that there are a number of RSV vaccines for the other population available in the market. There are no -- neither preventative or therapeutic options for HMPV. And maybe that's the virus that many of you even never heard about, but I can tell you that the RSV and HMPV are basically among leading causes of the severe respiratory infections. And if you look at the numbers of the hospitalization and infections are basically in the similar rate between HMPV, RSV and flu. And therefore, we feel excited to use this vaccines on 1 side, accelerate and bring it to patients as soon as possible.

因此，基本上，您可以從這些疫苗中看到的是具有更高的功效和更長的持久性，同時具有更好的安全性。第二個重要方面是，這是 RSV 和 HMPV 疫苗的組合。儘管有很多，但您可以爭辯說，市場上有許多針對其他人群的 RSV 疫苗。 HMPV 沒有預防或治療的選擇。也許你們中的許多人甚至從未聽說過這種病毒，但我可以告訴您，RSV 和 HMPV 基本上是嚴重呼吸道感染的主要原因。如果你看住院人數和感染率，HMPV、RSV 和流感的比率基本上相似。因此，我們對一方面使用這種疫苗感到興奮，並加速將其盡快帶給患者。

On the other side, it's a great strategic fit because it really builds on AztraZeneca experience in RSV as well as builds on our therapeutic leverage and serving the patients that are at risk of respiratory diseases. And just at the end, I need to mention that deal is still subject to closing.

另一方面，這是一個很好的策略契合，因為它確實建立在阿茲利康在RSV 方面的經驗基礎上，也建立在我們的治療槓桿和為有呼吸系統疾病風險的患者提供服務的基礎上。最後，我需要提到的是，交易仍有待完成。

So Lisa, your second question, the R&D spend, as we've said before, we expect to keep in the low 20s percentage as a percentage of revenue. And our improvement will come from SG&A. And so we are very committed to achieving this margin expansion in the midterm, as we've communicated for now quite some time. We are on track and we're committed to this and really is about leveraging the critical mass and some of these products that have required sorry, a lot of promotion at scale in terms of promotional efforts.

麗莎，你的第二個問題，正如我們之前所說，研發支出佔收入的百分比預計將保持在 20 左右。我們的改進將來自SG&A。因此，我們非常致力於在中期實現利潤率擴張，正如我們已經溝通了一段時間的那樣。我們正在走上正軌，我們致力於這一點，實際上是為了利用臨界質量和其中一些產品，抱歉，在促銷工作方面需要進行大量的大規模促銷。

If you look at the Breztri, look at -- I mean, Farxiga will be even potentially declining in promotion. So we can manage with this large SG&A spend. We have to manage, I should say, so that we can actually deliver this midterm ambition.

如果你看看 Breztri，看看——我的意思是，Farxiga 的晉級甚至可能會下降。因此我們可以管理如此大的銷售、管理及行政費用。我應該說，我們必須進行管理，以便我們可以真正實現這個中期目標。

Now the long-term ambition in operating margin is something we will define over the next couple of years as we see the progression of the pipeline. Because quite honestly, what we've seen in the last 2 to 3 years is an expansion of our pipeline.

現在，隨著我們看到管道的進展，我們將在未來幾年內定義營業利潤率的長期目標。因為老實說，我們在過去 2 到 3 年裡看到的是我們的管道的擴張。

We have a number of products now in the pipeline, the PCSK9, the (inaudible) of course, baxdrostat that we believe can drive a lot more top line growth than could have been anticipated, say, a couple of years ago. So depending on how the pipeline shapes up. We'll have to decide what our percentage margin ambition is, but I've said many times before, and I want to be clear, what we focus on is the absolute dollar value and the cash flow we deliver.

我們現在有許多產品正在開發中，PCSK9，當然還有（聽不清楚）baxdrostat，我們相信它可以推動比幾年前預期更多的營收成長。所以取決於管道的形狀。我們必須決定我們的利潤率目標是多少，但我之前已經說過很多次了，我想明確的是，我們關注的是絕對美元價值和我們提供的現金流。

So if we had -- and I'm not saying we would, but if we had to compromise on the further future progression of operating margin beyond the mid-30s, we had to comprise on the percentage, it will be because we deliver more top line. And the same or more absolute dollar value in operating profit and cash flow. Becasue ultimately as I keep saying we deliver value to shareholders with dollars not percentage, right? And so really, if we can deliver even more growth than we had anticipated 2 years ago, it will drive more profit.

因此，如果我們有——我並不是說我們會這樣做，但如果我們必須在30 多歲中期之後的營業利潤率的進一步發展上做出妥協，我們就必須在百分比上做出妥協，這將是因為我們提供了更多頂線。營業利潤和現金流的絕對美元價值相同或更高。因為最終正如我一直說的，我們用美元而不是百分比為股東提供價值，對吧？事實上，如果我們能夠實現比兩年前預期更高的成長，就會帶來更多利潤。

And so we'll have to adjust this over the next couple of years based on our pipeline. But with the firm commitment that in absolute value, we will deliver a substantial growth in top line but also in bottom line growth.

因此，我們必須在未來幾年內根據我們的管道進行調整。但憑藉絕對價值的堅定承諾，我們將實現營收和利潤的大幅成長。

Eric Le Berrigaud, Stifel. Two questions. First for Aradhana. Coming back on 1 of your comment before on CapEx. So CapEx anticipated to grow by maybe as much as 50%. How should we think about this going forward? Is it a 1-year sharp increase? Or should we think about CapEx staying around $2 billion for the next few years or thinking percentage of revenues? Or how should we model this?

埃里克·勒貝里戈，斯蒂菲爾。兩個問題。首先是阿拉達納。回到您之前關於資本支出的評論之一。因此，資本支出預計成長可能高達 50%。未來我們該如何思考這個問題？是1年大幅成長嗎？或者我們應該考慮未來幾年資本支出維持在 20 億美元左右，還是考慮佔收入的百分比？或者我們應該如何建模？

And maybe the second question for you, Ruud and Sharon, about maybe the next wave of innovation into the biologics in respiratory. We see 1 competition coming with long-acting [IO size] We see more interest for the TSLP targeting in -- also with long acting, but also combining with other targets. How -- what is AstraZeneca doing for the next wave and to build on the existing franchise?

Ruud 和 Sharon，也許第二個問題是關於呼吸系統生物製劑的下一波創新浪潮。我們看到 1 個長效 [IO 大小] 競爭即將到來。我們看到人們對 TSLP 的更多興趣——也具有長效，但也與其他目標相結合。阿斯特捷利康如何為下一波浪潮以及在現有特許經營的基礎上做些什麼？

Aradhana?

阿拉達納？

Sure. Thank you for the question. On CapEx, if you look over the last several years and you benchmark us against our peers, we've actually underinvested in CapEx substantially. And that's also because we had other opportunities to invest and so forth. But when you look forward, and especially this year, we've given guidance on specifically, we're investing behind a number of products that we're bringing forward, right? So we just announced the cell therapy facility in Rockwell. So again, Susan talked about the whole cell therapy ambition. That requires upfront investment in CapEx. And again, some of that is at risk, obviously. We're investing in our own API plant in Dublin. And that's also because we're trying to become more self-sufficient as it relates to API.

當然。感謝你的提問。在資本支出方面，如果你回顧過去幾年，並將我們與同行進行比較，你會發現我們實際上在資本支出上的投資嚴重不足。這也是因為我們有其他投資機會等等。但當你展望未來時，尤其是今年，我們已經給出了具體的指導，我們正在投資我們正在推出的許多產品，對嗎？所以我們剛剛宣佈在羅克韋爾建立細胞治療設施。蘇珊再次談到了整個細胞療法的雄心。這需要對資本支出進行前期投資。顯然，其中一些存在風險。我們正在都柏林投資建造自己的 API 工廠。這也是因為我們正在努力在 API 方面變得更加自給自足。

We announced a inhaled facility in Qingdao, and that's to fulfill the demand that we expect for breast free for example, to come out of China. And in addition, we are investing in our ERP systems, which as I would say, for many, many years being under invested in. So there are a number of these investments that we're making behind our pipeline. And you've seen from recent transactions and other investments that some of our peers are doing and have done that it has become increasingly important to have more and more self-reliant supply chains. And oftentimes, you see companies not being able to fulfill their growth ambition because of underinvestment in supply. So we're sort of getting ahead of this curve for the pipeline and the new opportunities.

我們宣佈在青島建立吸入設施，這是為了滿足我們預期的無母乳需求，例如來自中國的需求。此外，我們正在投資我們的 ERP 系統，正如我所說，多年來，該系統的投資一直不足。因此，我們正在我們的管道背後進行大量此類投資。從我們的一些同行正在做和已經做的最近的交易和其他投資中你可以看到，擁有越來越多的自力更生的供應鏈變得越來越重要。通常，您會看到公司由於供應投資不足而無法實現其成長目標。因此，我們在通路和新機會方面走在了這條曲線的前面。

One of the things that this plant in Qingdao, will support this our growth ambition in the respiratory market in China. If you look at COPD in China is totally underdeveloped. I mean the treatment is -- the disease is extremely prevalent, pollution, smoking, aging. So there's a lot of COPD, but the market is totally underdeveloped. Today, we have 65 or more percent market share with Breztri in the triple segment in China. And as the market develops, we're working very hard and expanding it as we market develop and we have local manufacturing, there's enormous potential for products like Breztri and that is really why we decided to make this investment.

青島工廠的其中一件事將支持我們在中國呼吸市場的成長野心。如果你看看慢性阻塞性肺病在中國是完全不發達的。我的意思是治療方法是──這種疾病非常普遍，污染、抽菸、老化。所以慢性阻塞性肺病很多，但市場完全不發達。如今，我們與 Breztri 在中國三重細分市場中擁有 65% 或更多的市場份額。隨著市場的發展，我們正在非常努力地工作並隨著市場的發展而擴大規模，並且我們擁有本地製造，像 Breztri 這樣的產品具有巨大的潛力，這就是我們決定進行這項投資的真正原因。

Quickly regarding, let's say, the future of the biologics, and Sharon will comment on the science in a moment. So despite the progress we have seen in the last few years was like Tezspire and Fasenra. It's also a fact of life that there's still a high unmet medical need and that remains. So still patients are suffering from multiple exacerbations in the severe asthma segment as well as COPD.

快速談論生物製品的未來，莎倫稍後將對科學進行評論。因此，儘管我們在過去幾年中看到了 Tezspire 和 Fasenra 等進步。生活中的一個事實是，仍然存在大量未滿足的醫療需求。因此，患者仍患有嚴重氣喘和慢性阻塞性肺病的多重惡化。

So we're going to bet on new mode of actions, [TNT] IL-33 is clearly 1 of the examples I'm sure Sharon will say a little bit more about that. But also, we have an anti-tSip in development. And it will be quite spectacular to have an inhaled biologic in order to help those patients suffering from a very severe disease. So new mode of actions, hopefully will unlock the power of those medicines and this indication. And you will see, I think, a lot of studies in the next few years, both in asthma and COPD in order to -- yes, to generate the evidence that it can work.

因此，我們將押注於新的行動模式，[TNT] IL-33 顯然是其中之一，我相信沙龍會對此多說一些。而且，我們正在開發一種反 tSip 技術。如果能有一種吸入性生物製劑來幫助那些患有非常嚴重疾病的患者，那將是相當壯觀的。因此，新的行動模式有望釋放這些藥物和這種適應症的功效。我想，在接下來的幾年裡，你會看到很多關於氣喘和慢性阻塞性肺病的研究，目的是——是的，產生它可以發揮作用的證據。

So I'll build on that and really continue forward with Ruud's message, in which we are proud of both following the science and thinking about patient needs as we create our next wave of therapeutics. So we're aware that patients with respiratory disease with asthma and COPD, are first treated in the community and then progressed to specialty care. And so we're creating a range of therapeutics that are able to meet the needs of their care providers, but also building on the science that we increasingly understand about these diseases.

因此，我將在此基礎上繼續推進 Ruud 的訊息，我們為在創造下一波治療方法時遵循科學並考慮患者需求感到自豪。因此，我們知道患有氣喘和慢性阻塞性肺病的呼吸系統疾病患者首先在社區接受治療，然後再接受專業護理。因此，我們正在創造一系列能夠滿足護理人員需求的治療方法，同時也建立在我們對這些疾病越來越了解的科學基礎上。

So in asthma, building on our success with Fasenra and Tezspire, we're moving forward to thinking about how tozorakimab can be effective there. Tozorakimab is a differentiated therapeutic in that this anti-IL-33 is hitting both the ST2 and the [RAGE ETFI] pathways. So it's able to address the inflammatory piece of the disease as well as mucus production and tissue remodeling, which we think is going to be very powerful for patients.

因此，在氣喘領域，在 Fasenra 和 Tezspire 取得成功的基礎上，我們正​​在繼續思考 tozorakimab 如何在氣喘領域中發揮作用。 Tozorakimab 是一種差異化治療藥物，因為這種抗 IL-33 同時作用於 ST2 和 [RAGE ETFI] 路徑。因此，它能夠解決疾病的發炎部分以及黏液產生和組織重塑，我們認為這對患者來說非常有效。

And thinking about how patients are accessing their care, moving into the prebiologic space with an inhaled T-slip which we think is a very novel mode of delivery and will allow us to broaden this modality to a larger number of patients as well as an inhaled JAK inhibitor and an oral FLAP inhibitor. So really expanding our science in the pre-biologic space.

並思考患者如何獲得護理，透過吸入 T 形片進入預生物空間，我們認為這是一種非常新穎的輸送方式，將使我們能夠將這種方式擴展到更多患者以及吸入式 T 形片。JAK抑制劑和口服FLAP​​ 抑制劑。所以真正在前生物領域擴展了我們的科學。

Thinking about COPD, which is still a major unmet medical need worldwide, building on our success with Breztri and again, thinking about how we're delivering an inhaled T-slip in the prebiologic space, offering patients those options as well as an IRAK4 inhibitor, and again, evaluating midiparstat in that space. So we are offering patients a number of different opportunities to address their disease with their general practitioners and then also to access biologics and different mechanisms as they're moving into specialty care. I hope that answers your question.

考慮 COPD，這仍然是全球未滿足的主要醫療需求，在 Breztri 的成功基礎上，考慮我們如何在益生元領域提供吸入 T-slip，為患者提供這些選擇以及 IRAK4 抑製劑，並再次評估該領域的midiparstat。因此，我們為患者提供許多不同的機會，讓他們與全科醫生一起解決他們的疾病，然後在他們進入專科護理時獲得生物製劑和不同的機制。我希望這能回答你的問題。

So again to add on the IL-33, it looks like even physicians have seen less data than -- from Saphnelo and from Roche from the Phase II, you're already into Phase III. Should we think about getting more Phase II this year or when are you planning to give more?

因此，再次添加 IL-33，看起來甚至醫生看到的數據也比來自 Saphnelo 和羅氏的 II 期數據要少，而您已經進入了 III 期。我們是否應該考慮今年獲得更多的第二階段資金，或者您計劃何時提供更多資金？

Yes, as you know we're so encourage by our data. We moved right to Phase III in that program and we'll look forward to sharing our Phase II data as it becomes available in our coming medical conference.

是的，如您所知，我們的數據讓我們深受鼓舞。我們已進入該計劃的第三階段，我們將期待在即將舉行的醫學會議上分享我們的第二階段數據。

So I've got two big ones ongoing. One is, the [INTL-33]. So in acute respiratory (inaudible) and hopefully we will see data after the next season. So somewhere in the next year. And if at all still fingers crossed, it will be the first than anti-IL33 in a complete new segment where there's a very big unmet medical need. The second one clearly our Phase III trial in the COPD space. We've added an additional arm, a high dose and that trial is ongoing and we'll read out in the next 2 years.

所以我有兩個大的事情正在進行中。其一是[INTL-33]。因此，在急性呼吸道疾病（聽不清楚）方面，希望我們能在下個賽季後看到數據。所以在明年的某個時候。如果仍然祈禱的話，它將成為一個全新領域中第一個比抗IL33更好的藥物，該領域存在著巨大的未滿足的醫療需求。第二個顯然是我們在慢性阻塞性肺病領域的第三階段試驗。我們增加了一個額外的手臂，一個高劑量，該試驗正在進行中，我們將在未來兩年內公佈結果。

Maybe we take the last question. Is that okay, Andy? So Gonzalo -- question on Gonzalo, at ABG.

也許我們回答最後一個問題。可以嗎，安迪？ Gonzalo——關於 ABG 的 Gonzalo 的問題。

Can you hear me?

你聽得到我嗎？

Yes.

是的。

Gonzalo from ABG Sundal Collier. I have a couple of questions. The first one is on Airsupra. It follows the previous question from the audience. And how big is the expected sales force and commercial team for Airsupra? And what is the current level of awareness of this drug from doctors today? Also in '23, you have been preparing for the launch of the drug. So what is the biggest challenge based on your experience through the year to penetrate the market that one could expect it to be quite conservative?

來自 ABG Sundal Collier 的貢薩洛。我有一些問題。第一個是 Airsupra。這是繼觀眾之前提出的問題之後的。 Airsupra 的預期銷售團隊和商業團隊有多大？目前醫生對這種藥物的認識程度如何？同樣在23年，你們一直在為該藥物的上市做準備。那麼，根據您一年來的經驗，進入市場所面臨的最大挑戰是什麼？人們可能會認為它是相當保守的？

And the second question is on Tagrisso. It seems from your report today that the demand in China had some issues with the hospital ordering dynamics. So could you give us some color on that? And how much is expected to affect 2024? And the same for the Australian government rebates looking also into '24 and beyond?

第二個問題是關於Tagrisso。從你今天的報告來看，中國的需求與醫院的訂購動態存在一些問題。那麼您能給我們一些說明嗎？預計對 2024 年影響有多大？澳洲政府的回饋也同樣適用於 24 世紀及以後的情況嗎？

Let me try to answer all the questions in a concise way. First of all, the field force, I'm not going to let's say, give you complete numbers, but it's a very substantial field for us. It's substantial for 2 reasons. We're detailing on the allergists as well as pulmonologists as well as we are detailing on a very large number of primary care physicians. Now the good news is that field force is a shared field force with Breztri. So we try to be very economically savvy in order to make sure that we're not going over the top.

讓我嘗試以簡潔的方式回答所有問題。首先，我不會說，現場人員給你完整的數字，但這對我們來說是一個非常重要的領域。它的重要性有兩個原因。我們正在詳細介紹過敏症專家和肺科醫師，以及我們正在詳細介紹大量初級保健醫生。現在好消息是，Field Force 與 Breztri 是共享的 Field Force。因此，我們努力在經濟上非常精明，以確保我們不會做得太過分。

The awareness, we have used 2023 to create a very substantial amount of awareness, the awareness is over 80% at the level of both the allergists and pulmonologists and especially allergists are the first prescribers. We started in a soft way in the last quarter. And last quarter, we had already 5,000 trialists, especially at the specialist level for Airsupra. Once again, the biggest challenge and that's the last question you were asking, what is not the headwind, but what is the biggest challenge?

意識，我們在 2023 年建立了非常大量的意識，過敏科醫生和肺科醫生的意識水平超過 80%，尤其是過敏科醫生是第一批處方者。我們在上個季度以溫和的方式開始。上個季度，我們已經有 5,000 名試用者，尤其是 Airsupra 的專家級試用者。再說一遍，最大的挑戰，這就是你問的最後一個問題，什麼不是逆風，但最大的挑戰是什麼？

The biggest challenge is we are very happy that the 3 large commercial PBMs have now listed Airsupra but there are multiple down streams, PBMs, and we still need to gain access there. There's nothing specific to Airsupra. It's just a fact of life of the U.S. environment. So we are working very diligently with our market access teams to -- or in order to create that access. And equally, we're going to bid for Part D in the course of this year as well.

最大的挑戰是我們很高興三大商業 PBM 現已上市 Airsupra，但還有多個下游 PBM，我們仍然需要在那裡獲得訪問權限。 Airsupra 沒有什麼特別之處。這只是美國環境的現實。因此，我們正在與我們的市場准入團隊非常努力地合作，以創造這種准入。同樣，我們也將在今年投標 D 部分。

Dave, Tagrisso.

戴夫，塔格里索。

Yes. So on Tagrisso within China, the fourth quarter hospital ordering dynamics we've seen for the last several years, and it just really has to do with hospitals managing their budgets as they come to the end of the calendar year, which is also the fiscal year. So it doesn't, for me, carry any weight into outlook for 2024. In fact, as I think about how we enter into 2024. Certainly, we continue to face competition, but where we don't face nearly as much competition is in the adjuvant setting.

是的。因此，就中國的泰瑞沙而言，我們在過去幾年中看到了第四季度的醫院訂單動態，這確實與醫院在日曆年末管理預算有關，這也是財政年度年。因此，對我來說，這對 2024 年的前景沒有任何影響。事實上，當我思考我們如何進入 2024 年。當然，我們繼續面臨競爭，但我們面臨的競爭沒有那麼激烈的是在輔助設置中。

I think it's important to remind that there's a sizable eGFR population within China. 30% to 40%. Also thoracic surgeons do have the ability to prescribe systemic therapies.

我認為有必要提醒大家，中國有相當多的 eGFR 族群。 30%到40%。胸腔外科醫師也有能力製定全身性治療方案。

So therefore, there's a relatively high adjuvant treatment rate, and we had ADAURA added into the NRDL with no discount. So I think that we come into the year with an opportunity to see growth in these really real demand side of things. And there are many fewer competitors that are playing within that adjuvant space. And our data, I think, stands as being the most impressive there.

所以輔助治療率比較高，我們把ADAURA無折扣的納入健保了。因此，我認為今年我們有機會看到這些真正需求的成長。而且在這個輔助空間中參與競爭的競爭對手要少得多。我認為我們的數據是最令人印象深刻的。

The Australia rebate reclassification is almost a direct offset between what you see on the Zoladex established Rest of World Beat and the Tagrisso Rest of World Beat, it's a -- mostly a onetime event. And I'd say mostly just because there's some carry on through the year, but I don't anticipate talking about it ever again.

澳洲回扣重新分類幾乎是您在 Zoladex 建立的世界其他地區節拍和 Tagrisso 世界其他地區節拍上看到的直接抵消，這是一個 - 大部分是一次性事件。我之所以這麼說，主要是因為今年有一些進展，但我預計不會再談論它。

Thank you, Dave. So thank you so much for your interest and your great questions. Maybe a few messages to close this meeting. .

謝謝你，戴夫。非常感謝您的興趣和提出的好問題。也許有幾條訊息可以結束這次會議。 。

The first one is just kind of taking into account all the questions asked today. First one is product sales in 2024. We will still have very strong product sales and the product sales will grow. I mean the growth of product sales in -- is coherent with the guidance we gave for top line revenue. So the clear message is, we are not dependent on collaboration revenue to grow in 2024. Our portfolio is doing very well, and all our geographies are doing very, very well.

第一個只是考慮到今天提出的所有問題。第一個是2024年的產品銷售。我們的產品銷售仍然非常強勁，產品銷售將會成長。我的意思是，產品銷售的成長與我們對營收的指導是一致的。因此，明確的訊息是，我們在 2024 年的成長並不依賴協作收入。我們的產品組合表現非常好，而且我們所有的地區都表現得非常非常好。

The second message is we are committed to this midterm operating margin, and it is, of course, challenging because as you've said, we have a very big portfolio and we have to invest in this growth, but we will get there. We are committed to this, and we are working towards this, making good progress. You saw the margin expansion in one of the slides, and we'll continue in that direction.

第二個訊息是我們致力於實現中期營業利潤率，這當然具有挑戰性，因為正如您所說，我們擁有非常大的投資組合，我們必須投資於這種成長，但我們會實現這一目標。我們致力於此，並正在為此努力，並取得良好進展。您在其中一張投影片中看到了利潤率的擴張，我們將繼續朝這個方向發展。

The third message maybe is, we believe we can manage through the Part D reform, and I mentioned it because I know some people have speculated this is going to be a big problem. It is a small headwinds. I mean, headwinds, we have headwinds constantly in one market or another, one product or another. The beauty of our pipeline and our footprint geographically is when 1 product face a headwind and other product picks up, remember, we have 13 products that are blockbuster status today. And 1 geography is struggling a bit another 1 is doing better, and that's really the model as we have it. But overall, Part D and we spent a lot of time, our teams have spent a lot of time working on modeling this.

第三個訊息可能是，我們相信我們可以透過 D 部分改革，我提到它是因為我知道有些人猜測這將是一個大問題。這是一個小逆風。我的意思是，逆風，我們在一個市場或另一個市場、一種產品或另一種產品上不斷遇到逆風。我們的產品線和我們的地理足跡的美妙之處在於，當一種產品面臨逆風而其他產品回升時，請記住，我們今天有 13 種產品處於重磅地位。 1 個地理區域正在掙扎，而另外 1 個地理區域則做得更好，這確實是我們擁有的模型。但總的來說，D 部分和我們花了很多時間，我們的團隊花了很多時間對此進行建模。

The incremental rebates that we will have to deal with is, first of all, in part compensated by the reduction of free goods, which is substantial for some of our oncology medicines. And overall, the net effect is certainly a negative, but it's really totally manageable in the context of our total global sales and the growth rate we are experiencing.

首先，我們必須處理的增量回饋部分是透過免費商品的減少來補償的，這對我們的一些腫瘤藥物來說意義重大。總的來說，淨效應肯定是負面的，但就我們的全球總銷售額和我們正在經歷的成長率而言，它確實是完全可以控制的。

And finally, but importantly, we are absolutely confident we can deliver a very strong long-term growth. And that's really what we want to show you and hopefully convince you at this R&D day, and I hope many of you will join us in the beautiful DISC, where we have tremendously talented teams that are doing a great job.

最後但重要的是，我們絕對有信心能夠實現非常強勁的長期成長。這確實是我們想要向您展示的內容，並希望在這個研發日說服您，我希望你們中的許多人能夠加入我們美麗的DISC，在那裡我們擁有非常有才華的團隊，並且做得非常出色。

We have today a huge number of collaborations in the Cambridge area, and this is really leading to very good productivity from our R&D efforts. With this, thank you very much. And again, thanks for your great questions.

今天，我們在劍橋地區進行了大量的合作，這確實為我們的研發工作帶來了非常好的生產力。在此，非常感謝。再次感謝您提出的好問題。