AstraZeneca PLC (AZN) 2025 Q3 法說會逐字稿

Good afternoon, and welcome to AstraZeneca's nine months and Q3 2025 webinar for investors and analysts. Before I hand over to AstraZeneca, I'd like to read the Safe Harbor statement. The company intends to utilize the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements with respect to the operations and financial performance of AstraZeneca.

下午好，歡迎參加阿斯特捷利康針對投資者和分析師的九個月及2025年第三季展望網路研討會。在將發言權交給阿斯特捷利康之前，我想先宣讀「安全港聲明」。公司擬採用1995年美國《私人證券訴訟改革法案》中的「安全港」條款。本次電話會議的參與者可能會就阿斯特捷利康的營運和財務表現發表前瞻性聲明。

Although we believe our expectations are based on reasonable assumptions, by their very nature, forward-looking statements involve risks and uncertainties and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these forward-looking statements. Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements. Please carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation and webcast. There will be an opportunity to ask questions after today's presentation. (Operator Instructions) And with that, I'd now like to hand the conference over to the Head of Investor Relations at AstraZeneca, Andy Barnett.

儘管我們相信我們的預期是基於合理的假設，但前瞻性陳述本質上涉及風險和不確定性，並可能受到各種因素的影響，導致實際結果與這些前瞻性陳述所明示或暗示的結果有重大差異。本次電話會議中所做的任何前瞻性陳述均反映了截至本次電話會議召開時可獲得的知識和資訊。本公司不承擔更新前瞻性陳述的義務。請仔細閱讀本次簡報和網路直播附帶的幻燈片中的前瞻性陳述免責聲明。今天的演示結束後將安排提問環節。 （操作說明）接下來，我將把會議交給阿斯特捷利康投資者關係主管安迪·巴內特先生。

A very warm welcome to AstraZeneca's year-to-date and third-quarter 2025 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 other members of our executive team, I'd like to cover some important housekeeping items. Firstly, all of the materials presented today are already available on our AstraZeneca Investor Relations website. Next slide, please. This slide contains our cautionary statements regarding forward-looking statements, including the Safe Harbor provision, which I'd encourage you to take the time to read carefully. We will be making comments on our performance is in constant exchange rates, or CER, core financial numbers and other non-GAAP measures.

歡迎各位投資人及分析師參加阿斯特捷利康2025年上半年及第三季業績電話會議及網路直播。我是投資者關係主管安迪·巴內特。在將發言權交給帕斯卡爾和其他高階主管團隊成員之前，我想先說明一些重要事項。首先，今天展示的所有資料都已發佈在阿斯特捷利康投資者關係網站上。請看下一張投影片。這張投影片包含我們關於前瞻性陳述的警示性聲明，包括「安全港」條款，請各位仔細閱讀。我們將以固定匯率（CER）計算的核心財務數據和其他非GAAP指標來闡述我們的業績。

A non-GAAP to GAAP reconciliation is as usual, contained within our results announcement. All numbers quoted are in millions of US dollars unless otherwise stated. And next slide, please. This slide shows the agenda for today's call. And following our prepared remarks, we'll open the line for questions. As usual, we will try and cover as many questions as we can during the allotted time, although please limit the number of questions that you asked to allow others a fair chance to participate in the Q&A. And with that, please advance to the next slide, and I will hand over to Pascal.

如往常一樣，我們的績效公告中包含非GAAP與GAAP的財務報表調節表。除非另有說明，所有數字均以百萬美元為單位。請看下一張投影片。這張投影片展示了今天電話會議的議程。在我們準備好的發言結束後，我們將開放提問環節。像往常一樣，我們會在規定的時間內盡可能多地回答問題，但請盡量減少提問數量，以便其他人也有機會參與問答。接下來，請看下一張投影片，我將把發言權交給帕斯卡爾。

Thank you, Andy, and welcome, everyone. I'm pleased to report that our strong growth momentum and pipeline delivery have continued through the first nine months of 2025. Total revenue grew by 11%, driven by continued demand for our innovative medicines and core EPS increased by 15%. Since our full year results in February, we've achieved 31 regulatory approvals across key regions and the pace at which we are bringing new medicines to patients continues to accelerate. Importantly, we've announced positive results from 16 Phase III trials and six of our data sets were presented in plenary sessions at major conferences, a clear reflection of the importance of this data to the medical community.

謝謝安迪，也歡迎各位。我很高興地報告，我們強勁的成長動能和產品線交付在2025年前九個月得以延續。總收入成長了11%，這主要得益於市場對我們創新藥物的持續需求；核心每股收益成長了15%。自2月發布全年業績以來，我們已在關鍵地區獲得了31項監管批准，並將新藥推向患者的步伐持續加快。更重要的是，我們公佈了16項III期臨床試驗的正面結果，並在重要會議的全體會議上展示了其中6項數據，這充分體現了這些數據對醫學界的重要性。

Please advance to the next slide. Combined, our global reach and diverse sources of revenue have significant strength, ensuring low concentration risk and resilience to regional disruptions. We have continued to deliver strong growth across therapy areas and geographies. In the first nine months, our oncology franchise grew by 16%, reflecting the ongoing demand for our medicines across the globe. Our biopharmaceuticals and Rare Disease franchises were also up 8% and 6%, respectively, with strong growth from our newer medicines more than offsetting the loss of exclusivity of a limited number of mature brands, including Brilinta, Pulmicort and Soliris. Importantly, we continue to see robust growth across all key geographies, particularly in the US and the emerging markets outside of China, where revenues were up 11% and 21%, respectively.

請翻到下一頁。我們遍佈全球的業務網絡和多元化的收入來源構成了強大的優勢，確保了較低的集中風險和抵禦區域性市場波動的能力。我們在各個治療領域和地區都持續實現了強勁成長。前九個月，我們的腫瘤業務成長了16%，反映了全球對我們藥物的持續需求。我們的生技和罕見疾病業務也分別成長了8%和6%，新藥的強勁成長足以彌補少數成熟品牌（包括Brilinta、Pulmicort和Soliris）失去獨家銷售權的影響。重要的是，我們在所有主要地區都持續保持強勁成長，尤其是在美國和中國以外的新興市場，這兩個市場的收入分別成長了11%和21%。

Please move to the next slide. We are in a unique catalyst rich period, one that I'm excited to say, look set to continue well beyond 2026. Shown here are the high-value positive studies we've announced in 2025. And as you can see, we are delivering success across all of our key therapy areas. Since our last quarterly update, we've announced four additional positive Phase III study readouts. DESTINY-Breast05 together with DESTINY-Breast11 that read out earlier this year marks an important advance for patients with early HER2-positive breast cancer that could potentially benefit from a HER2. TROPION-Breast02 has the potential to establish Datroway as a new standard of care in triple-negative breast cancer.

請翻到下一張投影片。我們正處於一個獨特的催化劑豐富的時期，我很高興地宣布，這段時期預計將持續到2026年以後。這裡展示的是我們已宣布將於2025年公佈的高價值積極研究。如您所見，我們在所有關鍵治療領域都取得了成功。自上次季度更新以來，我們又公佈了四項正面的III期研究結果。 DESTINY-Breast05以及今年稍早公佈結果的DESTINY-Breast11，對於可能受益於HER2抑制劑的早期HER2陽性乳癌患者而言，是一項重要的進展。 TROPION-Breast02可望將Datroway確立為三陰性乳癌的新標準療法。

The Bax24 trial results reinforce the best-in-class profile of baxdrostat in treatment-resistant hypertension. And finally, TULIP-Subcu will enable us to bring a more convenient subcutaneous administration of Saphnelo to SLE patients. All these positive Phase III readouts continue to give us confidence towards our $80 billion 2030 ambition. Next slide, please. I'd like to address recent developments for AstraZeneca in the United States. The US remains our largest market and is projected to account for around 50% of our total revenue by 2030. We announced a landmark agreement with the US government which provides greater clarity around pricing and a three-year exemption from tariffs.

Bax24 試驗結果進一步鞏固了巴司特在難治性高血壓治療領域的一流療效。此外，TULIP-Subcu 將使我們能夠為系統性紅斑狼瘡 (SLE) 患者提供更便捷的皮下注射沙菲諾 (Saphnelo) 方案。所有這些正面的 III 期臨床試驗結果都讓我們對實現 2030 年 800 億美元的營收目標充滿信心。請看下一張投影片。我想談談阿斯特捷利康在美國的最新進展。美國仍然是我們最大的市場，預計到 2030 年將占我們總收入的 50% 左右。我們宣布與美國政府達成一項里程碑式的協議，該協議提高了定價的透明度，並提供了為期三年的關稅豁免。

The agreement will lower the cost of many prescription medicines for American patients, while safeguarding Americas cutting-edge for pharmaceutical -- With the administration support, we are now working with others to deliver price equalization across wealthier markets, an approach that offers a more sustainable future for governments, industry and patients. In addition, we continue to focus on clinical trial diversity and further enhancing our clinical trial footprint in the US. To support our growth ambitions, we've been steadily expanding our global manufacturing capacity including broadening our US footprint over the last several years. Last month, I was pleased to break ground on our new Virginia facility joined by Senator, Lutnick; Governor, Youngkin; and Dr. Ross.

該協議將降低美國患者許多處方藥的成本，同時保障美國在製藥領域的領先地位。在政府的支持下，我們正與其他機構合作，在較富裕的市場中實現價格均衡，這項措施將為政府、產業和患者帶來更永續的未來。此外，我們將繼續致力於臨床試驗的多樣性，並進一步擴大我們在美國的臨床試驗規模。為了支持我們的成長目標，過去幾年我們一直在穩步擴大全球生產能力，包括擴大在美國的業務規模。上個月，我很高興與盧特尼克參議員、揚金州長和羅斯博士一起為我們在維吉尼亞州的新工廠舉行了奠基儀式。

And lastly, I'm grateful for our shareholders to voting through our proposal to harmonize our listing structure in London, Stockholm and New York. AstraZeneca's ordinary shares will be listed on the New York Stock Exchange from February next year. This new listing structure will offer flexibility to access the broadest available pool of capital, including in the US and enable more shareholders to participate in AstraZeneca's exciting future. And with that, please advance to the next slide, and I will hand over to Aradhana.

最後，我衷心感謝各位股東投票通過了我們關於統一倫敦、斯德哥爾摩和紐約上市結構的提案。阿斯特捷利康普通股將於明年2月起在紐約證券交易所上市。這個新的上市結構將使我們能夠更靈活地獲得更廣泛的資金，包括來自美國的資金，並使更多股東能夠參與阿斯特捷利康令人振奮的未來發展。接下來，請翻到下一張投影片，我將把發言權交給阿拉德哈娜。

Thank you, Pascal, and good morning, good afternoon, everyone. As usual, I will start with the reported P&L. Next slide, please. Total revenue increased by 11% in the first nine months. Product sales grew by 9% with strong growth seen across the business in key regions. Alliance revenue increased by 41%, driven by continued growth for both Enhertu and Tezspire in regions where our partners book product sales. Next slide, please. This is our core P&L. Our core gross margin in the first nine months was 83%. We continue to anticipate a slight decrease in the core gross margin for the full year versus 2024, due to the Medicare Part D reform, Brilinta LOE, Soliris biosimilars and increased profit sharing from partnered products.

謝謝帕斯卡爾，大家早安，下午好。照例，我先來看損益表。請看下一張投影片。前九個月總收入成長了11%。產品銷售額成長了9%，主要地區的業務整體成長強勁。聯盟營收成長了41%，這主要得益於Enhertu和Tezspire在合作夥伴銷售產品的地區的持續成長。請看下一張投影片。這是我們的核心損益表。前九個月的核心毛利率為83%。由於Medicare Part D改革、Brilinta的研發投入減少、Soliris生物相似藥以及合作產品利潤分成增加等因素，我們預計全年核心毛利率將略低於2024年的水平。

Similar to prior years, we anticipate the core gross margin in the fourth quarter to be lower than in the third quarter, driven by the usual seasonal pattern with more sales from lower-margin products like FluMist and Beyfortus. R&D expenses increased by 16% in the first nine months, driven by sustained high activity, including many clinical trials having enrolled ahead of plan. We've also made significant investments in high-value pipeline opportunities, such as our IO bispecifics, weight management and cell therapy portfolios.

與往年類似，我們預計第四季度核心毛利率將低於第三季度，這主要是受季節性因素影響，低利潤率產品（如FluMist和Beyfortus）的銷售額將增加。前九個月研發支出增加了16%，主要得益於持續高水準的研發活動，包括許多臨床試驗提前完成受試者招募。此外，我們也對高價值的研發管線進行了大量投資，例如我們的免疫腫瘤雙特異性抗體、體重管理和細胞療法產品組合。

As a percentage of total revenue, core R&D costs accounted for 23.3%, and we continue to expect R&D to land at the upper end of the low 20s% percentage range for the full year. We have continued to make progress towards our 2026 margin goal and remain on track, as you can see from our 9-month results with core operating margin at 33.3%. Operating leverage continues to remain a focus internally. And again, as you can see from the first nine months, broad revenue grew at 11% and SG&A grew at 3%. Core EPS of $7.04 represents CER growth of 15%. Next slide, please. We have seen strong cash flow inflow from operating activities in the year-to-date, up by 37% versus the prior year to $12.2 billion, driven by robust underlying business momentum. In the year-to-date, we saw CapEx of $2.1 billion. And as previously stated, we anticipate an increase of around 50% for the full year versus 2024, which implies a step-up in the fourth quarter which also is normal as in prior years.

核心研發成本佔總營收的23.3%，我們預期全年研發成本將維持在20%左右的區間上限。正如您從我們前九個月的業績中所見，我們持續朝著2026年的利潤率目標邁進，並保持著良好的發展勢頭，核心營業利潤率達到33.3%。營運槓桿仍然是我們內部關注的重點。此外，正如您從前九個月的業績中所見，總收入成長了11%，銷售、管理及行政費用成長了3%。核心每股收益為7.04美元，固定匯率成長率為15%。請看下一張投影片。今年迄今，我們經營活動產生的現金流入強勁，較去年同期成長37%至122億美元，主要得益於強勁的業務成長動能。今年迄今為止，我們的資本支出為21億美元。如同先前所述，我們預計全年將比 2024 年成長約 50%，這意味著第四季將出現成長，這與往年一樣正常。

Our capital allocation priorities remain unchanged. We currently have interest-bearing debt of close to $33 billion, which is a level we're comfortable with as we plan to continue making investments to support future growth, build our supply chain globally and further strengthen our R&D pipeline. Our net debt-to-EBITDA ratio currently stands at 1.2 times. Turning to guidance. Today, we are reiterating our full year guidance with total revenue and core EPS anticipated to increase by high single-digit and low double-digit percentage, respectively, at constant exchange rates. We expect our strong revenue momentum in growth brands to continue. I would like to remind you that in the fourth quarter of 2024, we booked more than $800 million in sales-based milestones under collaboration revenue.

我們的資本配置優先事項保持不變。我們目前的計息債務接近330億美元，我們認為這一水平尚可接受，因為我們計劃繼續投資以支持未來的成長，建立全球供應鏈，並進一步加強研發管線。我們目前的淨負債與EBITDA比率為1.2倍。接下來談談業績展望。今天，我們重申全年業績展望，預計總收入和核心每股收益將分別實現高個位數和低兩位數的百分比增長（按固定匯率計算）。我們預計成長型品牌的強勁營收動能將持續。我想提醒各位，在2024年第四季度，我們已確認超過8億美元的基於銷售額的合作收入里程碑。

This year, we do not anticipate any significant milestone revenue in the fourth quarter, which will affect the year-over-year growth rate comparisons for the fourth quarter. In addition, in China, while growth has been strong throughout the year, fourth quarter revenues are anticipated to be affected by VBP associates stock compensation costs for Farxiga, Lynparza and roxadustat and the usual year-end hospital budget capping in addition to tender order variability in emerging markets. Similar to prior years, we also anticipate a sequential step-up in both R&D and SG&A expenses in the fourth quarter versus the third quarter. With that, please advance to the next slide, and I will hand over to Dave, who will take you through the incredible performance of our oncology and hematology business.

今年，我們預計第四季不會有任何重大里程碑式的營收成長，這將影響第四季年增速的比較。此外，在中國，儘管全年成長強勁，但預計第四季度營收將受到VBP員工因Farxiga、Lynparza和roxadustat而產生的股權激勵成本、醫院年末預算上限以及新興市場招標訂單波動的影響。與往年類似，我們預期第四季研發及銷售、管理及行政費用將較第三季有所成長。接下來，請翻到下一張投影片，我將把發言權交給Dave，他將為大家介紹我們腫瘤和血液業務的卓越表現。

Thank you, Aradhana. Next slide, please. Oncology total revenue grew 16% in the first nine months to $18.6 billion with broad-based double-digit growth across US, Europe and emerging markets. The US, in particular, continued to report strong year-over-year growth of 19%, highlighting robust demand for our medicines, which substantially outpaced the increased liabilities resulting from Medicare Part D redesign. Emerging markets also delivered impressive performance with 20% growth during the period. Focusing on third quarter performance, we achieved robust 18% growth for the second quarter in a row. Tagrisso delivered sales of $1.9 billion in the third quarter, representing 10% growth on the prior year.

謝謝Aradhana。請看下一張投影片。腫瘤業務總收入在前九個月成長16%，達到186億美元，美國、歐洲和新興市場均實現了兩位數的全面成長。尤其值得一提的是，美國市場持續保持強勁的同比增長，達到19%，凸顯了市場對我們藥品的旺盛需求，這一增長遠超因聯邦醫療保險D部分改革而增加的負債。新興市場也表現出色，同期成長20%。第三季業績方面，我們連續第二季實現了18%的強勁成長。泰瑞沙（Tagrisso）第三季銷售額達19億美元，年增10%。

Widespread demand across all major regions reinforces Tagrisso's role as the backbone of care for EGFR-mutated lung cancer. The first-line lung cancer combination market continues to expand with FLAURA2 the clear leader in terms of new patient starts and total scripts. The compelling overall survival results presented at the World Congress of Lung Cancer and subsequently published in the New England Journal of Medicine will drive further leadership.

在所有主要地區的廣泛需求鞏固了泰瑞沙作為EGFR突變型肺癌治療基石的地位。第一線肺癌合併用藥市場持續擴張，FLAURA2在新患者起始治療量和處方總量方面均遙遙領先。在世界肺癌大會上公佈並隨後發表於《新英格蘭醫學雜誌》的令人矚目的總生存期結果，將進一步鞏固其領先地位。

Calquence remains the leading BTK inhibitor in first-line CLL across major markets, with total revenues increasing by 11% to $916 million in the third quarter. In the US, we continue to see increased demand more than offset the impact of Part D redesign with improved market share versus the same period last year. We're seeing positive early signs of adoption for AMPLIFY in Europe and expect this trajectory to continue through the remainder of the year with the US launch anticipated in the first half of 2026. Lynparza, which remains the leading PARP inhibitor globally delivered revenues of $837 million in the third quarter, up 5% year-on-year with consistent growth across key regions.

Calquence 仍然是主要市場第一線治療慢性淋巴球白血病 (CLL) 的領先 BTK 抑制劑，第三季總收入成長 11% 至 9.16 億美元。在美國，我們看到需求持續成長，足以抵消 D 部分重新設計的影響，市佔率較去年同期有所提升。 AMPLIFY 在歐洲的早期應用已呈現積極跡象，預計這一增長勢頭將在今年剩餘時間內持續，並預計於 2026 年上半年在美國上市。 Lynparza 仍然是全球領先的 PARP 抑制劑，第三季營收為 8.37 億美元，年成長 5%，並在主要地區保持了持續成長。

TruCap total revenues of $193 million in the third quarter represented 54% growth versus Q3 last year. With the AKT-P10 biomarker altered population almost fully penetrated, growth is now primarily driven by increased uptake of the PIK3CA population and ongoing launches in developed and emerging markets. This was another outstanding quarter for our IO franchise with growth of Imfinzi and Imjudo of 31% and 14%, respectively. We see continued enthusiasm for Imfinzi in the new lung indications, Adriatic and AGN and in bladder cancer with Niagara, alongside further expansion in our more established indications such as HIMALAYA and CASPIAN.

TruCap第三季總營收達1.93億美元，較去年同期成長54%。隨著AKT-P10生物標記突變人群的市場滲透率接近飽和，目前成長主要得益於PIK3CA人群的接受度提高以及在已開發市場和新興市場持續推出新產品。對於我們的免疫腫瘤產品線而言，本季度又是一個卓越的季度，Imfinzi和Imjudo分別實現了31%和14%的成長。我們看到Imfinzi在新的肺癌適應症Adriatic和AGN以及膀胱癌適應症Niagara方面持續受到市場歡迎，同時，HIMALAYA和CASPIAN等成熟適應症也得到了進一步拓展。

We are also starting to see early signs of adoption of MatTEHOn in the US following its Category 1 NCCN guideline inclusion and eagerly await regulatory decisions. ENHERTU total revenues grew 39% in the third quarter with ongoing launches of the DESTINY-Breast06 indication, further strengthening our leadership position in HER2-low metastatic breast cancer. The strong initial uptake in China following NRDL enlistment has persisted through Q3 as we achieve even broader coverage and continue to drive adoption. Positive readouts across HER2-positive breast cancer at ASCO and ESMO are anticipated to further drive growth with data now spanning across the spectrum of HER2-positive disease. And finally, Datroway continues to make inroads in hormone receptor positive breast cancer across the US and Europe.

在MatTEHOn被納入NCCN指南1類適應症後，我們已開始看到其在美國的早期應用跡象，並熱切期待監管機構的最終決定。 ENHERTU第三季總營收成長39%，這得益於DESTINY-Breast06適應症的持續上市，進一步鞏固了我們在HER2低表現轉移性乳癌的領先地位。自從獲批國家藥品上市計畫（NRDL）以來，MatTEHOn在中國市場的強勁初期成長勢頭延續至第三季度，我們進一步擴大了市場覆蓋範圍，並持續推動其應用。 ASCO和ESMO大會上HER2陽性乳癌的積極數據預計將進一步推動成長，目前的數據已涵蓋HER2陽性疾病的各個方面。最後，Datroway在美國和歐洲的荷爾蒙受體陽性乳癌市場也持續取得進展。

And this quarter, we have started to see encouraging early signals of uptake in the previously treated EGFR-mutated lung cancer space following US approval and NCCN guideline inclusion. We are confident in carrying our strong performance from the first nine months through to year-end as we continue to expand the reach of our innovative medicines. With that, please advance to the next slide, and I'll pass over to Susan to cover key R&D highlights from the quarter.

本季度，在美國獲準並納入NCCN指引後，我們已開始看到EGFR突變肺癌患者（先前接受過治療）的早期接受度呈現令人鼓舞的上升趨勢。我們有信心將前九個月的強勁業績延續到年底，並繼續擴大我們創新藥物的覆蓋範圍。接下來，請翻到下一張投影片，我將把麥克風交給Susan，讓她介紹本季研發的主要亮點。

Thank you, Dave. Just over two weeks ago at the European Society of Medical Oncology, AstraZeneca delivered multiple pivotal data sets with the potential to reshape clinical practice, including 2 featured in presidential sessions. This underscores the quality and breadth of our science and reinforces AstraZeneca's leadership in bringing new advances to patients worldwide. DESTINY-Breast11 and 05 advanced ENHERTU into the early treatment setting for HER2-positive breast cancer, highlighting its potential to become a foundational therapy in early disease and ultimately increasing the likelihood that more patients could be cured of breast cancer. In DESTINY-Breast11, treatment with ENHERTU followed by THP prior to surgery resulted in a pathologic complete response rate of 67% in patients with high-risk HER2-positive early-stage breast cancer, the highest ever reported rate in the Phase III registrational trial in this setting.

謝謝戴夫。就在兩週多前，在歐洲腫瘤內科學會（ESMO）年會上，阿斯特捷利康公佈了多項關鍵數據，這些數據有望重塑臨床實踐，其中兩項數據在主席會議上重點介紹。這凸顯了我們科學的品質和廣度，並鞏固了阿斯特捷利康在為全球患者帶來最新進展方面的領先地位。 DESTINY-Breast11 和 05 研究將 ENHERTU 推進到 HER2 陽性乳癌的早期治療領域，凸顯了其成為早期疾病基礎療法的潛力，並最終提高更多乳癌患者的治癒率。在 DESTINY-Breast11 研究中，高風險 HER2 陽性早期乳癌患者接受 ENHERTU 治療後，在手術前接受 THP 方案治療，病理完全緩解率達到 67%，這是該適應症 III 期註冊試驗中報告的最高緩解率。

We also saw an early trend towards an event-free survival benefit with ENHERTU followed by THP. Importantly, this regimen demonstrated a favorable safety profile versus the five-drug ACTHP regimen with lower rates of grade three or higher adverse events, serious adverse events and treatment interruptions. This makes DESTINY-Breast11 the first regimen in over a decade to significantly improve outcomes in the earliest treatment setting for HER2-positive breast cancer, and these data are now under FDA review. In DESTINY-Breast05, ENHERTU reduced the risk of disease recurrence or death by 53% compared to T-DM1 in patients with high-risk HER2-positive early breast cancer following neoadjuvant therapy, with over 92% of patients treated with ENHERTU free of invasive disease at three years. This data set offers a critical second opportunity to reduce recurrence risk in this patient population.

我們也觀察到，ENHERTU 聯合 THP 方案在無事件存活期方面具有早期獲益趨勢。重要的是，與五藥合併 ACTHP 方案相比，此方案展現出良好的安全性，三級以上不良事件、嚴重不良事件和治療中斷的發生率均較低。這使得 DESTINY-Breast11 成為十多年來第一個在 HER2 陽性乳癌早期治療階段顯著改善療效的方案，目前這些數據正在接受 FDA 審查。在 DESTINY-Breast05 研究中，與 T-DM1 相比，ENHERTU 使接受新輔助治療的高風險 HER2 陽性早期乳癌患者的疾病復發或死亡風險降低了 53%，接受 ENHERTU 治療的患者中超過 92% 在三年時未出現侵襲性疾病。該數據集為降低此類患者群體的復發風險提供了至關重要的第二次機會。

Taken together, DESTINY-Breast11 and 05 have the potential to transform early-stage HER2-positive breast cancer by reducing metastatic recurrence and bringing patients closer to cure, and this represents a blockbuster opportunity across the alliance. We also shared data from the TROPION-Breast02 trial, which evaluated Detroay versus chemotherapy as a first-line treatment for patients with locally recurrent inoperable or metastatic triple-negative breast cancer for whom immunotherapy is not an option.

DESTINY-Breast11 和 05 兩項研究結果相結合，有望透過降低轉移復發率、提高治癒率，徹底改變早期 HER2 陽性乳癌的治療格局，這對整個聯盟而言都是一個意義重大的機會。我們也分享了 TROPION-Breast02 試驗的數據，該試驗評估了 Detroay 與化療作為一線治療方案，用於治療局部復發、無法手術或轉移性三陰性乳癌且不適合接受免疫療法的患者。

These patients typically have poor outcomes with the current standard of care and five-year overall survival rates of just 15%. TB02 included those with the poorest prognosis often excluded from clinical trials, such as patients with a short disease-free interval and those presenting with brain metastases at baseline. In TB02, Detroway delivered an unprecedented five-month improvement in median overall survival versus chemotherapy, along with a statistically significant and clinically meaningful 43% reduction in the risk of disease progression or death. In addition, almost two-thirds of patients experienced a complete or partial response to Dataay, double the rate seen with chemotherapy, alongside a manageable safety profile, low rates of discontinuation and no treatment-related deaths. These data clearly differentiate Datroay and together with its convenient three-weekly dosing, position it to reshape the TNBC landscape for the 70% of first-line patients who are not suitable for immune checkpoint inhibitors.

這些患者通常接受現有標準治療後預後不良，五年總存活率僅15%。 TB02研究納入了預後最差的患者，這些患者通常被排除在臨床試驗之外，例如無疾病存活期短的患者以及基線時已出現腦轉移的患者。在TB02研究中，與化療相比，達特羅韋（Datroay）使中位總生存期延長了前所未有的五個月，同時疾病進展或死亡風險降低了43%，這一結果具有統計學意義和臨床意義。此外，近三分之二的患者對達特羅韋有完全或部分緩解，緩解率是化療的兩倍，且安全性良好，停藥率低，無治療相關死亡。這些數據清楚顯示達特羅韋的優勢，加上其便捷的三週一次給藥方案，使其可望重塑三陰性乳癌（TNBC）一線治療格局，惠及70%不適合接受免疫檢查點抑制劑治療的患者。

Our other key Phase III readout at ESMO was POTOMAC. This trial moves Imfinzi into earlier-stage bladder cancer, demonstrating that adding one year of Imfinzi to BCG induction and maintenance therapy delivers both early and sustained disease-free survival benefits with a 32% reduction in risk of recurrence or death compared to BCG alone in high-risk non-muscle invasive bladder cancer. With this Imfinzi regimen, 87% of patients remained alive and disease-free at two years, highlighting its potential to change the trajectory for these patients and further building on ImfIza's impact in muscle-invasive disease as shown in Niagara.

我們在ESMO大會上發表的另一項關鍵III期臨床試驗結果是POTOMAC。該試驗將Imfinzi應用於早期膀胱癌，結果表明，在BCG誘導和維持治療的基礎上加用一年Imfinzi，可顯著延長高危險非肌層浸潤​​性膀胱癌患者的無病生存期，與單獨使用BCG相比，復發或死亡風險降低32%。在使用Imfinzi方案治療的患者中，兩年後仍有87%存活且無病生存，這凸顯了該方案改變患者預後的潛力，並進一步鞏固了Imfinzi在肌層浸潤性膀胱癌治療中的療效，正如Niagara試驗所顯示的那樣。

These results reinforce the strength of our bladder program, and we very much look forward to data from the Volga trial in cisplatin-ineligible muscle invasive bladder cancer, which is now expected in the first half of next year. In addition, we presented Phase III data from CAPTELA-281 for TruCap in combination with abiraterone and androgen deprivation therapy in PTEN-deficient metastatic hormone-sensitive prostate cancer. Taken together, these pivotal data sets strongly support our strategy to advance novel therapies into earlier-stage disease where they have the greatest potential to improve patients' lives.

這些結果進一步鞏固了我們膀胱癌計畫的實力，我們非常期待明年上半年公佈的伏爾加河試驗（Volga trial）的數據，該試驗針對的是不適合順鉑治療的肌層浸潤性膀胱癌。此外，我們也發表了CAPTELA-281 III期臨床試驗的數據，該試驗評估了TruCap合併阿比特龍和雄性素剝奪療法治療PTEN缺陷型轉移性荷爾蒙敏感性前列腺癌的療效。總而言之，這些關鍵數據有力地支持了我們的策略，即推動新型療法在疾病早期階段的研發，因為這些療法在早期階段最有可能改善患者的生活品質。

We also presented significant new data at ESMO across our early programs, including first-in-human results for our folate receptor alpha ADC, AZD5335 or toorvuam in platinum-resistant relapsed ovarian cancer. New data for our PARP1 selective inhibitor, soraparib, in combination with androgen receptor pathway inhibitors in metastatic prostate cancer, updated findings for rilvegostamig in checkpoint inhibitor naive lung cancer, which compares favorably to current PD-1-based therapies and encouraging new results for the combination of rilvegostamig and Dataway in bladder cancer. All these results build our confidence in the long-term strength of our pipeline, positioning us to deliver innovation well beyond 2030.

在ESMO大會上，我們也發表了早期研發計畫的重要新數據，包括葉酸受體α抗體偶聯藥物AZD5335（或稱toorvuam）在鉑類抗藥性復發性卵巢癌中的首次人體試驗結果；PARP1選擇性抑制劑索拉帕尼合併雄激素受體通路抑制劑治療轉移性前列腺癌的新數據；利維戈司他米在未接受過免疫檢查點抑制劑治療的肺癌中的最新研究結果，該結果與目前基於PD-1的療法相比具有優勢；以及利維戈司他米聯合Dataway治療膀胱癌的令人鼓舞的新結果。所有這些結果都增強了我們對研發管線長期實力的信心，使我們能夠在2030年後持續提供創新療法。

Before closing, I want to highlight the upcoming American Society of Hematology Meeting in December, where we will present updates of our CD19/CD3 T-cell engager, suruvatamib, and our CD19 BCMA dual CAR-T AZZD0120. These pipeline assets both have $5 billion-plus non-risk-adjusted peak year revenue potential, and we will build our position in hematologic malignancies with the opportunity to set new standards across this space. And with that, please advance to the next slide, and I'll pass over to Ruud to cover biopharmaceuticals performance.

在結束之前，我想重點介紹即將於12月舉行的美國血液學會年會，屆時我們將報告CD19/CD3 T細胞銜接器suruvatamib和CD19 BCMA雙靶點CAR-T療法AZZD0120的最新進展。這兩個在研產品均具有超過50億美元的非風險調整後高峰年收入潛力，我們將藉此機會鞏固我們在血液系統惡性腫瘤領域的地位，並有望在該領域樹立新的標竿。接下來，請翻到下一張投影片，我將把發言權交給Ruud，他將介紹生物製藥業務的表現。

Thank you so much, Susan. Next slide, please. Our biopharmaceuticals medicines delivered a strong performance in the year-to-date with total revenue reaching $17.1 billion, reflecting growth of 8% -- starting with R&I, we saw growth of 40% in the quarter, driven by strong performances across our inhaled and biologic portfolio. The growth medicines now constitute over 60% of the therapy areas revenue and have grown at an impressive rate of 30% year-to-date. Our products now make up half the new-to-brand prescriptions for the severe asthma biologics segment in several markets. Fasenra continues to lead in eosinophilic asthma. We were pleased to see growth accelerating to 20% in the quarter with Fasenra's product profile being strengthened by uptake in EGPA and our first revenues from China.

非常感謝蘇珊。請看下一張投影片。今年迄今，我們的生物製藥業務表現強勁，總營收達到171億美元，年增8%。其中，研發業務在本季實現了40%的成長，這主要得益於我們吸入製劑和生物製劑產品組合的強勁表現。增長型藥物目前佔治療領域收入的60%以上，今年迄今的成長率高達30%。在多個市場，我們的產品目前佔據了重度氣喘生物製劑新處方量的一半。 Fasenra在嗜酸性粒細胞性氣喘領域繼續保持領先地位。我們很高興看到，隨著Fasenra在嗜酸性粒細胞性肉芽腫性血管炎（EGPA）領域的應用以及我們在中國市場的首次收入，該領域的成長在本季度加速至20%。

TeZpire continued its rapid market share gains in severe asthma with 47% growth in the quarter. Its growth potential has been further enhanced by recent approvals in the United States and the EU for chronic rhinositis with nasal polyps based on the WAPOIN trial, which demonstrated a significant reduction in nasal polyp size and nearly eliminated the need for surgery. Breastri grew at 20%, driven by market share gains in the growing triple class. All revenues today come from COPD patients, and we have now filed regulatory submissions for asthma in all major regions following the positive readouts from the CALOSLOS trials.

TeZpire在重度氣喘領域持續維持快速市佔率成長，本季成長47%。其成長潛力進一步增強，這得益於近期在美國和歐盟獲批用於治療慢性鼻息肉伴鼻息肉，該批准基於WAPOIN試驗，該試驗表明TeZpire能顯著縮小鼻息肉體積，並幾乎完全消除手術需求。 Breastri成長20%，主要得益於其在成長快速的三重氣喘治療領域市佔率的提升。目前所有收入均來自慢性阻塞性肺病（COPD）患者，根據CALOSLOS試驗的正面結果，我們已在所有主要地區提交了氣喘治療的監管申請。

We are pleased to receive a positive CHMP recommendation for our next-generation propellant, which has 99.9% lower global warming potential, a key milestone towards our company's sustainability goals. Breasttri will be the first of our inhaled medicines to transition to the next-generation propellant. SAnelo, our biologic medicine for SLE, continues to win share in the intravenous segment of the market and grew at 44% in the quarter. In September, we announced positive high-level results based on the interim analysis from the TULIP subcutaneous study, which paves the way for Sanela to reach SLE patients who prefer a subcutaneous option.

我們很高興收到人用藥品委員會 (CHMP) 對我們新一代推進劑的積極推薦，該推進劑的全球暖化潛能值降低了 99.9%，這是我們公司實現永續發展目標的重要里程碑。 Breasttri 將成為我們第一個過渡到新一代推進劑的吸入藥物。我們用於治療系統性紅斑狼瘡 (SLE) 的生物製劑 SAnelo 在靜脈注射市場份額持續成長，本季成長率達 44%。 9 月，我們公佈了基於 TULIP 皮下注射研究中期分析的積極高級別結果，這為 SAnelo 惠及偏好皮下注射的 SLE 患者鋪平了道路。

TULIPSC recently received a positive CHMP recommendation in the EU. Total revenue from the CVR therapy area was flat in the quarter, reflecting the loss of exclusivity for Brilinta, which saw a revenue decline of 56%. Farxiga delivered 8% growth despite a slight decline in Europe due to the earlier-than-expected entry of generic competition in the United Kingdom. Lokelma grew 30%, maintaining its leading share in the potassium binder class for chronic kidney disease and heart failure patients. In anticipation of further growth for Lcalma, we were excited to have recently opened an expanded manufacturing facility in Texas. In addition to the strong product performances in the year-to-date, I'm also particularly excited to see the number of high-value biopharma trials due to readout in 2026. And with that, I will now hand over to Sharon to discuss the latest developments for Baxdrostat, the next NME we anticipate to launch in biopharma with more than $5 billion peak year revenue potential.

TULIPSC近期獲得了歐盟人用藥品委員會（CHMP）的積極推薦。本季度，CVR治療領域的總收入持平，這主要反映了Brilinta的專利保護期結束，導致其收入下降了56%。儘管由於仿製藥在英國的上市時間早於預期，導致歐洲市場略有下滑，但Farxiga仍實現了8%的成長。 Lokelma成長了30%，繼續保持其在慢性腎臟病和心臟衰竭患者鉀結合劑領域的領先地位。為了進一步提升Lokelma的銷售量，我們很高興地宣布，近期我們在德州開設了一家擴建後的生產工廠。除了今年迄今強勁的產品表現外，我還特別期待看到許多高價值生物製藥試驗將於2026年公佈結果。接下來，我將把發言權交給Sharon，讓她來介紹Baxdrostat的最新進展。 Baxdrostat是我們預計在生物製藥領域推出的下一個新分子實體，其年收入高峰潛力超過50億美元。

Thank you, Rud. Next slide, please. At AstraZeneca, our ambition is to transform care across interconnected cardiorenal and metabolic diseases where multiple risk drivers and organ systems overlap. Hypertension is a key part of this challenge. And in the past 20 years, there has been very limited innovation. For example, around half of patients currently treated in the US remain uncontrolled while on multiple medicines. Baxdrostat is designed precisely for these patients.

謝謝，魯德。請看下一張投影片。在阿斯特捷利康，我們的目標是革新相互關聯的心臟腎臟和代謝疾病的治療，這些疾病涉及多種風險因素和器官系統重疊。高血壓是這項挑戰的關鍵組成部分。過去20年，這方面的創新非常有限。例如，目前在美國接受治療的患者中，約有一半即使服用多種藥物，血壓仍未控制。 Baxdrostat 正是為這些患者而設計的。

As a reminder, Baxdrostat is a once-daily, highly selective and potent aldosterone synthase inhibitor, targeting the aldosterone pathway at its source. Excess aldosterone is well established as a driver of hypertension and broader cardiorenal disease. By limiting aldosterone production, baxdrostat provides a clean targeted mechanism that has the potential to enable more patients to reach their treatment goals, particularly those with uncontrolled or resistant hypertension.

需要提醒的是，巴克司他是一種每日一次、高選擇性且強效的醛固酮合成酶抑制劑，可從源頭抑制醛固酮路徑。過量的醛固酮已被證實是高血壓和更廣泛的心腎疾病的驅動因素。巴克司他透過限制醛固酮的生成，提供了一種精準的標靶機制，有望幫助更多患者達到治療目標，特別是那些難治性或未控制的高血壓患者。

In the third quarter, we presented the first Phase III data for baxdrostat monotherapy with the BAX-HTN trial at the European Society of Cardiology. We were also delighted to report the positive high-level results for the Phase III VAX-24 trial. Collectively, these readouts reinforce our confidence in baxdrostat's more than $5 billion potential as a franchise. In the BAX-HTN trial for patients with uncontrolled and treatment-resistant hypertension on maximally tolerated background therapy, Baxdrostat delivered the largest systolic blood pressure reduction reported in a primary analysis to date.

第三季度，我們在歐洲心臟學會年會上公佈了baxdrostat單藥治療的首個III期臨床試驗數據—BAX-HTN試驗。同時，我們也欣喜地報告了III期臨床試驗VAX-24試驗的正高階結果。這些結果共同增強了我們對baxdrostat作為一項具有超過50億美元市場潛力的藥物的信心。在BAX-HTN試驗中，對於接受最大耐受劑量背景治療後仍存在難治性高血壓的患者，baxdrostat實現了迄今為止主要分析中報告的最大收縮壓降低幅度。

At 12 weeks, placebo-adjusted reductions were 8.7 and 9.8 millimeters of mercury on the 1 and 2 milligram doses, respectively. Responses were highly consistent across prespecified subgroups, and we saw a powerful target engagement with a 60% to 65% reduction in serum aldosterone at week 12. Importantly, this reduction was sustained over time. Furthermore, in the randomized withdrawal period, patients continuing baxdrostat saw further reductions in blood pressure out to 32 weeks. Baxdrostat also demonstrated a favorable tolerability profile. Adverse events were mostly mild with no off-target hormonal effects and no clinically relevant drug-drug interactions observed. Confirmed hyperkalemia above 6 millimole per liter was 1.1% in both dose arms, and we saw low discontinuation rates of 0.8% and 1.5% for the 1- and 2-milligram doses, respectively. 24-hour control of hypertension matters clinically. Early morning blood pressure variability is strongly correlated to the risk of cardiovascular events, so sustained control of blood pressure between doses is important. Baxdrostat's long half-life is a key differentiator in an ambulatory sub-study of BaxHTN, we saw substantial reductions in 24-hour average and nighttime systolic blood pressure. Building on this, we recently reported positive high-level results from the Phase III Bax24 trial, which was conducted in the most difficult-to-treat patients, those with resistant hypertension.

在第12週，安慰劑校正後的血壓在1毫克和2毫克劑量組分別降低了8.7毫米汞柱和9.8毫米汞柱。預設亞組的療效高度一致，且在第12週時，血清醛固酮濃度顯著降低了60%至65%，顯示藥物標靶作用強勁。重要的是，這種降低效果能夠持續。此外，在隨機停藥期內，繼續服用巴司特（baxdrostat）的患者血壓進一步降低，直到第32週。巴司特也表現出良好的耐受性。不良事件大多為輕度，未觀察到脫靶激素效應和具有臨床意義的藥物交互作用。兩個劑量組中，血鉀濃度高於6毫摩爾/公升的確診高血鉀發生率均為1.1%，1毫克和2毫克劑量組的停藥率分別為0.8%和1.5%。 24小時血壓控制在臨床上至關重要。清晨血壓波動與心血管事件風險密切相關，因此，兩次給藥之間血壓的持續控制非常重要。 Baxdrostat的長半衰期是其關鍵優勢。在BaxHTN的一項動態亞研究中，我們觀察到24小時平均血壓和夜間收縮壓均顯著降低。在此基礎上，我們近期發表了III期Bax24試驗的積極高級別結果，該試驗針對的是最難治療的患者－難治性高血壓患者。

In Bax24, baxdrostat demonstrated a statistically significant and highly clinically meaningful reduction in ambulatory 24-hour average systolic blood pressure. Efficacy was observed across the entire 24-hour period, including early morning. We look forward to sharing you exciting data with the medical community at the American Heart Association this coming weekend. These results solidify baxdrostat's potential as a first and best-in-class option for patients with uncontrolled and resistant hypertension, offering convenient once-a-day dosing with sustained blood pressure control around the clock. We are advancing our regulatory filings and rapidly progressing our robust clinical development program for baxdrostat, both as a monotherapy and in combination with dapagliflozin. And with that, please proceed to the next slide, and I'll pass over to Marc to cover rare disease.

在 Bax24 研究中，baxdrostat 顯著降低了 24 小時動態平均收縮壓，且具有高度臨床意義。療效在整個 24 小時內均有觀察到，包括清晨。我們期待在本週末的美國心臟協會年會上與醫學界分享這些令人振奮的數據。這些結果鞏固了 baxdrostat 作為一線且同類最佳的治療方案的潛力，適用於難治性高血壓患者，每日一次給藥即可實現全天候持續血壓控制。我們正在推進 baxdrostat 的監管申報工作，並快速推進其強大的臨床開發項目，包括單藥治療和與達格列淨聯合用藥。接下來，請看下一張投影片，我會把麥克風交給 Marc，讓他介紹罕見疾病。

Thank you, Sharon. Can I get the next slide, please? Rare Disease medicine grew 6% to $6.8 billion in the first nine months of the year, driven by growth in neurology indications, increased patient demand and continued global expansion. In the third quarter, Ultomiris grew 17%, driven by patient demand growth across indication, including the competitive gMG and PNH markets. Soliris revenues continues to decline due to the successful conversion to Ultomiris as well as biosimilar pressure in Europe. Strensiq grew 28% and Koselugo grew by 79%, respectively, due to strong underlying demand for these medicines. Koselugo's growth also benefited from some tender orders in emerging markets.

謝謝莎倫。請給我下一張投影片好嗎？今年前九個月，罕見疾病藥物銷售額成長6%，達到68億美元，主要得益於神經系統疾病適應症的成長、患者需求的增加以及全球市場的持續擴張。第三季度，Ultomiris成長17%，主要得益於各適應症（包括競爭激烈的重症肌無力和陣發性睡眠性血紅素尿症）的患者需求成長。由於成功轉換為Ultomiris以及歐洲生物相似藥的壓力，Soliris的收入持續下降。 Strensiq和Koselugo分別成長28%和79%，主要得益於市場對這些藥物的強勁需求。 Koselugo的成長也受惠於新興市場的一些招標訂單。

We continue to see great momentum across the rare disease portfolio with recent approval for Koselugo and Ultomiris that further our geographic reach for this medicine. Please advance to the next slide. We presented data from our Phase III PREVAIL trial, investigating gefurulimab on our dual branding nanobody targeting C5 in patients with generalised myasthenia gravis. Gefurulimab demonstrated 1.6 point improvement from baseline, placebo adjusted in myasthenia gravis activities of the living total score at week 26. The MG-ADL total score change from baseline reached 4.2 points at week 26 in the gefurulimab-treated patients.

我們罕見疾病產品組合持續保持強勁勢頭，Koselugo 和 Ultomiris 近期獲準進一步擴大了該類藥物的地域覆蓋範圍。請翻到下一張投影片。我們展示了 III 期 PREVAIL 試驗的數據，該試驗研究了針對 C5 的雙品牌奈米抗體 gefurulimab 在重症肌無力患者中的療效。在第 26 週，與安慰劑組相比，接受 gefurulimab 治療的患者重症肌無力生活活動總評分 (MG-ADL) 較基線改善 1.6 分。接受 gefurulimab 治療的患者在第 26 週的 MG-ADL 總評分較基線改善達 4.2 分。

A clinically meaningful improvement in MG-ADL total score was observed as early as week 1 and was sustained through week 26. Gefurulimab demonstrated rapid, complete and sustained complement inhibition. Gefurulimab also met all secondary endpoints, including quantitative myasthenia gravis total score where gefurulimab demonstrated a 2.1 point improvement at week 26 compared to placebo. A prespecified measurement at week 4 also made statistical significance, again demonstrating the rapid onset of action of gefurulimab in patient with GMG. The PREVAIL trial was conducted in a broader GMG patient population compared with prior trials of C5-targeted therapies. Gefurulimab is a convenient, self-administered subcutaneous once-a-week treatment with the potential for two delivery option, a pre-fill syringe and auto injector, which would be the first in GMG.

在第1週即觀察到MG-ADL總分的臨床意義顯著改善，並持續至第26週。格夫魯利單抗表現出快速、完全且持續的補體抑製作用。格夫魯利單抗也達到了所有次要終點，包括重症肌無力定量總評分，在第26週時，格夫魯利單抗較安慰劑組提高了2.1分。第4週的預設測量值也具有統計意義，再次證明了格夫魯利單抗在GMG患者中起效迅速。與以往C5標靶療法的試驗相比，PREVAIL試驗納入了更廣泛的GMG患者族群。格夫魯利單抗是一種方便的、可自行皮下注射的每週一次的治療方法，並有可能提供兩種給藥方式：預充式註射器和自動注射器，這將是GMG治療領域的首創。

We believe that the strength of this data and convenient administration, gefurulimab has a potential to become a new first-line therapy following immunosuppressive therapies. I also wanted to update on other important Phase III data we had this year. Analysis of the 52 weeks results on the CALYPSO trial to further characterize eneboparatide are ongoing. We will continue monitoring these patients in the open-label extension. For anselamimab, we have shared clinical results from the Phase III CARES program with regulatory authorities.

我們相信，憑藉這些數據的可靠性和便捷的給藥方式，格夫魯利單抗有望成為免疫抑制療法後的新型一線治療方案。我還想向大家報告我們今年獲得的其他一些重要的III期臨床試驗數據。 CALYPSO試驗52週結果的分析正在進行中，以進一步闡明依那帕肽的特性。我們將繼續在開放標籤擴展研究中監測這些患者。關於安塞拉米單抗，我們已將III期CARES計畫的臨床結果提交給監管機構。

Following further discussion, we plan to submit for the pre-specified patient subgroup in which anselamimab demonstrated a highly significant improvement in both time to mortality and frequency of cardiovascular utilization compared to placebo. And finally, efzimfotase alfa, we expect to announce results from all Phase III studies, HICKORY, CHESTNUT and MULBERRY in the first half of next year. Together, these three trials cover patients across pediatric, adolescent and adult hypophosphatasia population. And with that, please advance to the next slide, and I will hand over to Pascal.

經過進一步討論，我們計劃提交針對預先設定的患者亞組的申請，在該亞組中，與安慰劑相比，安塞拉米單抗在延長生存時間和降低心血管治療頻率方面均顯示出顯著改善。最後，關於依非莫他酶α，我們預計明年上半年公佈所有III期研究（HICKORY、CHESTNUT和MULBERRY）的結果。這三項試驗涵蓋了兒童、青少年和成人低磷酸酯酶症患者。接下來，請翻到下一張投影片，我將把發言權交給帕斯卡爾。

Thank you, Marc. Next slide, please. As I mentioned at the start of this call, we are in the midst of an unprecedented catalyst switch period one which is anticipated to extend through 2026 and beyond. We look forward to exciting readouts in each of our key therapy areas in 2026, which on a combined basis represent a risk -- Sorry, risk-adjusted PKR revenue opportunity of more than $10 billion. Our exceptional performance for the first nine months so has delivered a core operating margin of 33.3%. This is a clear demonstration that despite the opportunities to invest in this rich pipeline, we remain committed to driving operating leverage and we remain on track for both our 2026 margin target of mid-30s and our $80 billion 2030 revenue ambition.

謝謝馬克。請看下一張投影片。正如我在本次電話會議開始時提到的，我們正處於前所未有的催化劑轉換期，預計這段時期將持續到2026年及以後。我們期待在2026年獲得各個關鍵治療領域令人振奮的數據，這些領域合計代表著超過100億美元的風險調整後PKR收入機會。我們前九個月的優異表現也帶來了33.3%的核心營業利益率。這清楚地表明，儘管我們擁有豐富的研發管線，但我們仍然致力於提升營運槓桿，並有望實現2026年30%左右的利潤率目標和2030年800億美元的營收目標。

Next slide, please. In closing, I'm very pleased to report that we are making excite growth across our transformative technologies, which have the potential to drive AstraZeneca's growth well beyond 2030. We are moving at pace with our oral PCSK9 inhibitor, laroprovstat. And now we have three Phase III trials ongoing, and we are looking forward to the results from our Phase II trials across our weight management portfolio next year. We're driving forward with our ADC and our radioconjugate portfolio with the first Phase III of our wholly owned ADC sone-vedo reading in the first half of next year.

請看下一張投影片。最後，我非常高興地報告，我們在各項變革性技術方面取得了令人振奮的成長，這些技術有望推動阿斯特捷利康在2030年後持續成長。我們的口服PCSK9抑制劑拉羅普司他(laroprovstat)的研發進展迅速。目前，我們有三個III期臨床試驗正在進行中，並期待明年公佈體重管理產品組合II期臨床試驗的結果。我們的抗體偶聯藥物(ADC)和放射性偶聯藥物產品組合也在穩步推進，我們自主研發的ADC藥物sone-vedo的首個III期臨床試驗結果將於明年上半年公佈。

Supporting our ambition to replace current immune checkpoint inhibitors with next generation bispecifics, we now have 14 Phase III trials underway for rilvegostomig and volrustomig. And we are continuing to strengthen our hematology portfolio with our first Phase III trial already underway for our CD19 CD3 T-cell engager surovatamig, and we are planning to advance CD9, BCMA, CAR-T, AZD0120 into Phase III next year. And lastly, our first gene therapy is now entering the clinic. And with that, please advance to the next slide, and we will move to the Q&A. As Andy mentioned at the start of the call, please limit the number of questions you ask to allow others offer chance to participate. For those online, please use the raise hand function on Zoom, and with that, let's move to the first question.

為了實現以新一代雙特異性抗體取代現有免疫檢查點抑制劑的目標，我們目前正在進行 14 項針對 rilvegostomig 和 volrustomig 的 III 期臨床試驗。同時，我們也持續加強血液疾病產品組合，首個針對 CD19 CD3 T 細胞銜接器 surovatamig 的 III 期臨床試驗已經啟動，併計劃明年將 CD9、BCMA、CAR-T 療法 AZD0120 推進至 III 期臨床試驗。最後，我們的首個基因療法也即將進入臨床階段。接下來，請翻到下一張投影片，我們將進入問答環節。正如 Andy 在會議開始時所提到的，請盡量減少提問數量，以便其他人也有機會參與。線上與會者請使用 Zoom 的舉手功能。現在，讓我們進入第一個問題。

As Andy mentioned at the start of the call, please limit the number of questions you ask to allow others offer chance to participate. For those online, please use the raise hand function on Zoom, and with that, let's move to the first question.

正如安迪在通話開始時提到的，請盡量減少提問數量，以便其他人也有機會發言。線上的各位請使用Zoom的舉手功能。那麼，我們就開始第一個問題吧。

Michael Leuchten, Jefferies.

Michael Leuchten，傑富瑞集團。

Two questions for you, please. One, thank you for the comments around the environment in Washington. Just wondering if you could comment on what is the risk of residual activity coming from the administration? How confident are you that the deal that AstraZeneca has managed to secure removes enough of the overhang? So we don't have to look over our shoulders constantly as we think about R&D productivity and the cost of innovation. And the second question for you, Pascal, the $10 billion number that you just mentioned in terms of the catalyst potential coming out of the '27/'28 period. Is that part of the $80 billion? Or is that incremental potential already on top of that?

請容許我問您兩個問題。第一，感謝您之前對華盛頓環境問題的評論。我想請您談談政府後續政策可能帶來的風險。您對阿斯特捷利康達成的協議能否消除足夠的隱患有多大信心？這樣我們在考慮研發效率和創新成本時，就不必時時提心吊膽了。第二個問題，帕斯卡爾，您剛才提到的2027/2028年期間的100億美元催化劑潛力，是包含在800億美元中嗎？還是說這部分新增潛力已經包含在800億美元了？

So, the first question, what I would say about this is that we have addressed the four points in the President's letter. And the four points, as you know, the covered Medicaid, they cover prospective, equalization, direct to consumer and also returning to the US government, some of the potential price increases for existing products. And so, we've covered all of this. So, now our expectation is that essentially, we have an agreement with the US government, and we don't expect anything more to come. But of course, we are not the government, so we cannot guarantee anything. We can only say that our expectation from the discussions we've had, our expectation is that this agreement is delivering what the President was looking to achieve. On the $10 billion, this is part of our $80 billion.

首先，關於這個問題，我想說的是，我們已經解決了總統信中提到的四點。如您所知，這四點包括：醫療補助計劃（Medicaid）的覆蓋範圍、預期價格調整、均衡化、直接面向消費者以及將部分現有產品的潛在價格上漲返還給美國政府。我們已經處理了所有這些問題。因此，我們預計，我們基本上已經與美國政府達成了協議，並且預計不會再有其他進展。當然，我們不是政府，所以我們無法做出任何保證。我們只能說，根據我們先前的討論，我們預期這項協議能夠實現總統希望達成的目標。至於100億美元，這是我們800億美元計畫的一部分。

This is, by the way, not a 2030 number. It's a peak year revenue number. It's your risk adjusted $10 billion. But certainly, it will contribute to achieving our 2030 ambition. There is more to come. We have a number of readouts next year and we expect from the reader to expect another $10 billion -- actually $11 billion of risk-adjusted sales to come out of these readouts, assuming, of course, they are positive, we could get even more. So, as I said before, it is quite unprecedented for us as a company to have such a rich series of readout across not only oncology but also hematology, cardiovascular

順便一提，這並非2030年的數字，而是高峰年份的營收數字，也就是經過風險調整後的100億美元。當然，這將有助於我們實現2030年的目標。未來還有更多驚喜。明年我們將公佈一系列數據，我們預計這些數據將帶來另外100億美元——實際上是110億美元的風險調整後銷售額。當然，前提是這些數據都是正面的，如果結果積極，我們甚至可能會獲得更多。正如我之前所說，對於我們公司而言，能夠同時在腫瘤學、血液學和心血管領域公佈如此豐富的數據，實屬前所未有。

(technical difficulty) meaningfully treatment guidelines long term? And then also just your thoughts on whether any new simple diagnostic tests are coming soon to potentially expand the cardiomyopathy population? .

（技術難題）長期治療指引是否具有實質意義？另外，您認為近期是否會有新的簡單診斷測試出現，從而有可能擴大心肌病變患者族群？

So Sharon, do you want to cover and Ruud if you have anything to add please jump in.

Sharon，你想補充什麼嗎？ Ruud，如果你有什麼要補充的，請隨時發言。

Sure. So, we look forward to the readout of the Phase III CARDIO-TTRansform study in 2026. Do we have the potential to meaningfully transform that treatment algorithm for patients? I think what we're able to demonstrate with the CARDIO-TTRansform study is both the role of silencers in adequately treating disease and in a planned subset, key secondary endpoint readout will be looking at the effect of iplentresin in patients who have tafamidis. And so that will give us the opportunity to be able to address that key question for patients comparing the effect of silencer plus stabilizer versus silencer, which I think will be very important in guiding patient treatment decisions.

當然。我們期待2026年公佈的III期CARDIO-TTRansform研究結果。我們是否有可能真正改變患者的治療方案？我認為CARDIO-TTRansform研究能夠證明的是，抑制劑在充分治療疾病方面的作用，並且在計劃的子集中，一項關鍵的次要終點指標將考察伊普崙瑞辛對接受他法米地治療的患者的影響。這將使我們有機會解答患者的關鍵問題：抑制劑合併穩定劑與單獨使用抑制劑的效果有何不同？我認為這對於指導患者的治療決策至關重要。

And then finally, AstraZeneca is in a unique position in developing new therapies for patients living with ATTR amyloidosis and that we also have Alexion 2220, the amyloidosis depleter in our portfolio. And we continue to work towards creating a combination approach of a depleter and a silencer, which we think could be truly pivotal for patients living with ATTR amyloidosis. Now with regards to diagnosis, we know that's a key part of the patient journey. And we know that this is not simply a hereditary disease. The hereditary variants are rare, but the disease is not.

最後，阿斯特捷利康在開發ATTR澱粉樣變性患者的新療法方面擁有獨特的優勢，我們產品組合中還包括澱粉樣變性清除劑Alexion 2220。我們正持續致力於研發清除劑和抑制劑的聯合療法，我們認為這對ATTR澱粉樣變性患者至關重要。關於診斷，我們深知這是患者治療過程中的關鍵環節。我們也知道，這並非單純的遺傳性疾病。雖然遺傳變異較為罕見，但這種疾病本身並不罕見。

This is also a disease of the aging. So being able to screen for and detect patients earlier in their disease progression will be really fundamental to offering patients improved outcomes. So to that end, we are exploring a number of different opportunities to be able to more accurately and earlier diagnose ATTR amyloidosis. And those include AI-informed models that allow us to identify patients on screening with echocardiogram or potentially EKG as well as developing new biomarker assays to be able to detect soluble amyloid. So we continue to work on all fronts to be able to drive both earlier detection and earlier treatment.

這也是一種與老化相關的疾病。因此，能夠在疾病早期階段篩檢和檢測患者對於改善患者的治療效果至關重要。為此，我們正在探索多種途徑，以期更準確、更早診斷ATTR澱粉樣變性。這些途徑包括利用人工智慧模型，透過超音波心動圖或心電圖篩檢來識別患者，以及開發新的生物標記檢測方法來檢測可溶性澱粉樣蛋白。我們正持續在各方面努力，以期實現更早的發現和治療。

Thanks, Sharon. Ruud, anything you wanted to add or...

謝謝，莎倫。魯德，你還有什麼要補充的嗎？

No. just like everyone, everyone is eagerly waiting for the results. hasn't mentioned yet by Sharon is that this is the largest CM trial so far in cardiomyopathy -- and if successful, hopefully, we will see a CV mortality benefit, which, of course, is extremely important for treating cardiologists. Now on top of that, we are very pleased to see let's say, the progress we are making in the first indication, the PN indication. So we can only hold for patients and also for the company and other interested that the ATTR-CM trial will be positive, and we will know that in the course of 2026.

不，就像所有人一樣，大家都在熱切地等待結果。莎倫還沒提到的是，這是迄今為止規模最大的心肌病變臨床試驗——如果成功，我們希望能夠看到心血管死亡率的益處，這對心臟科醫生來說當然至關重要。此外，我們也很高興地看到，例如，我們在第一個適應症，即PN適應症方面，取得了進展。因此，我們只能對患者、公司和其他相關人士抱持希望，ATTR-CM試驗將會是正面的，我們將在2026年內得知結果。

Sachin Jain, Bank of America.

Sachin Jain，美國銀行。

I've got one each for Sharon and Susan on Phase III starts you've each referenced. So for Sharon, I wonder if you could just remind us of the obesity portfolio, the oral and amylin as we look for Phase II data next year. How are you thinking about your target competitive profile given the competitive landscape has rapidly changed. Obviously, with oral, we've seen the ortho data since you last presented and with Amylin, we've had the Lilly data out today. And then for Susan, I think you referenced the Phase III start for the BCMA CAR-T, where we see data at ASH of 5 billion peak. Just looking at the abstract, it looks like you've got 100% MRD negativity in almost fourth-line patients. So just wondering how you're thinking about the fastest route to market for that and beyond efficacy, how you're seeing differentiation on safety and administration.

我分別想問Sharon和Susan一個關於你們各自提到的III期臨床試驗啟動的問題。 Sharon，我想請你簡單介紹一下你們的肥胖症產品組合，包括口服藥物和胰淀素，因為我們明年就要看到II期臨床試驗的數據了。鑑於競爭格局的快速變化，你們是如何看待目標競爭格局的？顯然，口服藥物方面，自從你上次報告以來，我們已經看到了骨科的數據；而胰淀素方面，禮來公司今天也公佈了數據。 Susan，我想你提到了BCMA CAR-T療法的III期臨床試驗啟動，我們在ASH會議上看到了峰值達到50億的數據。從摘要來看，你們在幾乎四線治療的患者中實現了100%的微小殘留病灶（MRD）陰性。所以我想知道你們是如何考慮最快上市的，除了療效之外，你們是如何看待安全性和給藥方式的差異化的。

Thank you. Sharon, do you want to start? And then Susan?

謝謝。莎倫，你想先開始嗎？然後是蘇珊？

Sure. So Sachin, as you know, we are moving forward with multiple molecules in our management portfolio. That is AZD5004 that's currently in Phase II for patients with obesity and type 2 diabetes. AZD6234, that's our long-acting amylin peptide, subcutaneous injectable that is also in Phase II for the same patient populations and ACD9550, and that's our dual GLP-1 glucagon receptor agonist, also subcutaneous injectable also in Phase II. As we move all three of these forward at pace, of course, we're looking to have highly competitive molecules that give us reason to believe that these could be valuable treatment options for patients.

當然。薩欽，如你所知，我們正在推動多個分子藥物的研發。其中包括目前處於II期臨床試驗階段的AZD5004，它針對肥胖症和第2型糖尿病患者。 AZD6234是一種長效型胰淀素勝肽，皮下注射劑，也處於II期臨床試驗階段，同樣針對上述患者族群。 ACD9550是一種雙重GLP-1胰高血糖素受體激動劑，也是皮下注射劑，同樣處於II期臨床試驗階段。我們正快速推動這三個項目的研發，當然，我們希望獲得極具競爭力的分子，並相信它們能夠為患者提供有價值的治療選擇。

As we move forward, we're also thinking about the potential for market segmentation, and we know that there will be room for multiple mechanisms. And the bar is high. We've seen the very interesting data from alorlintide today. And so that gives us more reason to believe that a selective amylin receptor agonist similar to 6234 has the potential for efficacy in terms of weight loss and better sugar control for patients with type 2 diabetes. So, we have seen no red flags to date and continue to move forward at pace and expect to enter Phase III pending competitive data and we will be making those decisions in 2026.

展望未來，我們也在考慮市場區隔的可能性，我們知道多種機制都有存在的空間。而且，標準很高。今天我們看到了阿洛林肽非常令人振奮的數據。這讓我們更有理由相信，類似於6234的選擇性胰淀素受體激動劑，在減輕體重和改善第2型糖尿病患者的血糖控制方面具有潛在療效。因此，到目前為止，我們還沒有發現任何危險訊號，並將繼續快速推進，預計將在獲得競爭性數據後進入III期臨床試驗，我們將在2026年做出相關決定。

So, in terms of the 0120, which is the CD19 BCMA dual CAR, thanks for the question, Sachin. We will be presenting data in the later-line patient population at ASH. This includes patients who are triple-class refractory and a substantial proportion that have had prior BCMA CAR-T therapy. So what the data show is that we do have a really impressive response rates and complete response rates in evaluable patients that are also progressing, and they tend to evolve over time. There's a relatively small number of patients that are currently MRD evaluable, but you rightly point out in that small number in the abstract, all of them have achieved MRD negativity.

關於 CD19 BCMA 雙 CAR-T 療法 0120，感謝 Sachin 的提問。我們將在 ASH 會議上公佈後線患者族群的數據。這包括第三線抗藥性患者，以及相當一部分先前接受過 BCMA CAR-T 療法的患者。數據顯示，在可評估的進展期患者中，我們獲得了非常可觀的緩解率和完全緩解率，而且這些緩解率會隨時間推移而變化。目前可進行 MRD 評估的患者數量相對較少，但正如您在摘要中指出的，在這少數患者中，所有患者都已達到 MRD 陰性。

The overall profile of this cell is as dosed is attractive. We have no Grade 3 CRS and no ICANS in the data set that we've presented in the abstract. And I think the -- both the efficacy and the safety profile is related in part to the FasTCAR manufacturing, which Gracell had developed, which is helping to deliver this predictable CRS profile and deep and early responses. So we're very excited about the prospects for this. And we want to reiterate that we're going to start Phase III trials for this next year. And again, we'll be taking this forward in multiple settings in multiple myeloma.

這種細胞的整體特性，無論劑量如何，都非常吸引人。在我們摘要中展示的資料集中，沒有出現3級細胞激素釋放症候群（CRS）或免疫細胞性抗腫瘤反應（ICANS）。我認為，其療效和安全性部分歸功於Gracell公司開發的FasTCAR生產工藝，有助於實現可預測的CRS特徵以及深度和早期緩解。因此，我們對該療法的前景感到非常興奮。我們想重申，我們將在明年啟動該療法的III期臨床試驗。此外，我們將繼續在多發性骨髓瘤的多種治療方案中推進該療法的研究。

Thank you, Susan. The next question is from Richard Vosser at JPM.

謝謝你，蘇珊。下一個問題來自摩根大通的理查德·沃瑟。

Two questions, please. Firstly, one, just following up on the TB02HAHA data at ESMO. Maybe you could talk about the read across from the better tolerability you showed relative to competing products there, both to your DAA trials, but also more importantly, across the other ADC programs, what can we learn from that? And then secondly, maybe a more commercial rollout question. Just the Imfinzi or Imfinzi sales were very, very strong this quarter. I wonder if you could give a little bit more color on the rollouts. You highlighted bladder and lung, but how should we think about the runway of growth from here for Imfinzi?

請容許我問兩個問題。首先，我想跟進ESMO大會上公佈的TB02HAHA資料。您能否談談，您在ESMO大會上展現出的優於競爭產品的耐受性，對於您的DAA試驗以及更重要的ADC項目，我們能從中汲取哪些經驗教訓？其次，我想問一個關於商業推廣的問題。本季Imfinzi的銷售業績非常強勁。能否詳細介紹一下Imfinzi的推廣情況？您重點提到了膀胱癌和肺癌，那麼我們該如何看待Imfinzi未來的成長前景？

Susan, do you want to cover the first one? And David, the Imfinzi rollouts question?

蘇珊，你想負責第一個問題嗎？還有大衛，關於Imfinzi的推廣問題？

Sure. Thanks for the question. So yes, we're delighted with the TROPION-Breast02 data that was presented at ESMO. And I think this does speak to the actual design of this ADC, which similar to the Enhertu design is based on linker stability. So it's really important to have linker stability so that you're actually delivering a higher proportion of the payload actually to the tumor cells and less exposure in the peripheral circulation. That drives the difference in terms of the bone marrow toxicity profile that you see with D2A compared to some other TROP2-based ADCs. And I think that also speaks to the fact that we then delivered a higher response rate, longer progression-free survival and this 5-month improvement in overall survival, which I think is a differentiated profile.

當然。謝謝你的提問。是的，我們對在ESMO大會上公佈的TROPION-Breast02數據感到非常滿意。我認為這確實體現了這款ADC的實際設計，它與Enhertu的設計類似，都是基於連接子的穩定性。因此，保持連接子的穩定性至關重要，這樣才能確保將更高比例的有效載荷遞送到腫瘤細胞，並減少其在周邊循環中的暴露。這正是D2A與其他一些基於TROP2的ADC相比，在骨髓毒性方面表現出差異的原因。我認為這也解釋了我們為何能獲得更高的緩解率、更長的無惡化存活期以及總存活期延長5個月，我認為這是一種差異化的療效。

So that -- first of all, within the breast cancer space, it increases the confidence in the early-stage studies, the TROPIN-Breast03, which is in the post neoadjuvant setting, a little bit analogous to the DESTINY-Breast05 setting. And that's in combination, of course, with Imfinzi. -- the TROPION-Breast04 setting, which is in the neoadjuvant treatment of P4negative breast cancer and then TROPION-Breast05, which takes that doublet combination of Dat2A and Imfinzi also into the first-line setting. So with those studies, plus, of course, the lung cancer studies, the AVANza studies, I think the profile that we've got is one that we're confident about, and we look forward to having the future readouts in the coming months and years.

首先，在乳癌領域，這增強了我們對早期研究的信心，例如TROPIN-Breast03研究，該研究針對新輔助治療後的治療，與DESTINY-Breast05研究的治療方案有些類似。當然，DESTINY-Breast05研究也採用了達托黴素（Dat2A）和伊芬那嗪（Imfinzi）合併治療。此外，TROPION-Breast04研究針對P4陰性乳癌的新輔助治療，而TROPION-Breast05研究則將達托黴素和伊芬那嗪的雙藥合併方案應用於第一線治療。因此，結合這些研究，以及肺癌研究和AVANza研究，我認為我們目前掌握的療效數據令人鼓舞，我們期待在未來幾個月和幾年內獲得更多研究結果。

Thanks, Susan. With respect to the Imfinzi growth drivers in '25 and outlook moving forward, I think it has really been a great example of delivery against multiple new life cycle expansion opportunities. The primary growth drivers have been with Adriatic and small cell, Age in early lung cancer and then also Niagara has also been an important area of growth. All three of those represent opportunities for us to continue to see full year benefits across the globe as we launch those. Now there is competitive pressures that we face on all of those. With that said, our differentiation, I think, is strong and our first-mover advantage is clear. I would also just point out that very importantly, we've got positive studies with MATTERHORN with strong overall survival that was presented at ESMO. We've got PETOMIC. Those are both studies that we are looking forward to hopefully achieving regulatory approvals across the globe. And there will be further readouts as well that we have coming forward from here. So the Imfinzi trajectory is one that has been both strong and I anticipate will be sustained.

謝謝Susan。關於Imfinzi在2025年的成長驅動因素和未來展望，我認為它確實是把握多個新的生命週期拓展機會並取得成功的絕佳範例。主要的成長驅動因素是Adriatic和小細胞肺癌、早期肺癌的Age，Niagara也是一個重要的成長領域。隨著這些藥物在全球範圍內的上市，我們有望繼續獲得全年收益。當然，我們在所有這些領域都面臨著競爭壓力。儘管如此，我認為我們的差異化優勢依然強勁，先發優勢也顯而易見。我還想特別指出，我們在ESMO大會上公佈了MATTERHORN研究的積極結果，該研究顯示總生存期顯著延長。我們也有PETOMIC研究。我們期待這兩項研究都能在全球範圍內獲得監管部門的批准。此外，我們也會陸續公佈更多研究結果。因此，Imfinzi的發展軌跡一直非常強勁，我預計這種勢頭將會持續下去。

Peter Verdult, Exane.

Peter Verdult，Exane。

Peter Verdult here, BNP. Apologies for any background noise. Two questions for Pascal. I thought it was noteworthy at the investor event the ESMO cancer event. You called out baxdrostat in your opening remarks. KOLs that we're speaking to, say, they see sort of placebo-adjusted blood pressure lowering in sort of 11, 12, 13 range. Their excitement around this asset is going to be cranked up. So, I know you can't talk to the data. We're going to have to wait until Sunday.

我是法國巴黎銀行的Peter Verdult。如有背景噪音，請諒解。我有兩個問題想問Pascal。在ESMO癌症投資人活動上，您開場白中提到了baxdrostat，我覺得這一點很值得關注。我們訪談的一些KOL表示，他們觀察到，該藥物在安慰劑校正後的血壓下降幅度在11、12、13左右。他們對這款藥物的期望值肯定會很高。我知道您目前無法提供具體數據，我們得等到週日才能看到結果。

But when you look at consensus expectations down at $2 billion, would you expect that expectations for this asset materially increase post the Bax24 data? And then secondly, we've talked about the political environment in the US I mean the industry wants to and has to invest more in the US wants to invest more in China. Where is that leaving Europe? I mean Europe, what's the political environment in Europe? Are the politicians waking up to the direction of travel. Do you think that the innovation debate can be genuinely had in Europe? Or are you more you say, sanguine about the outlook of -- regarding innovation being paid for in Europe?

但考慮到市場普遍預期僅20億美元，您認為在Bax24數據公佈後，市場對該資產的預期會大幅提升嗎？其次，我們之前討論過美國的政治環境，我的意思是，產業希望並且必須加大對美國的投資，而美國也希望加大對中國的投資。那麼歐洲的情況又如何呢？歐洲的政治環境如何？政界人士是否已經意識到發展的方向？您認為歐洲能夠真正就創新展開討論嗎？或者，您對歐洲創新資金來源的前景持更樂觀的態度？

Thank you, Peter. So, let me start with baxdrostat and then maybe I'm sure the we're very excited about this product. We want to add some more. I'm personally very excited about this product because not only because hypertension uncontrolled hypertension is a big problem. A lot of people are on three drugs and still uncontrolled. That drives skin disease, heart disease, cardiovascular events. So that's a big unmet need, much, much bigger than people understand really.

謝謝你，彼得。那麼，我先來說說巴克司他（baxdrostat），然後我想說，我們對這款產品非常興奮。我們還想補充一些其他資訊。我個人對這款產品非常興奮，因為高血壓控制不佳是一個大問題。很多人服用三種藥物，血壓仍然沒有控制。這會導致皮膚病、心臟病和心血管事件。所以這是一個巨大的未滿足需求，遠比人們想像的要嚴重得多。

The second reason is the effect on aldosterone, the 60%, 65% reduction that Sharon mentioned a bit earlier, I think will prove over time a massive benefit because although aldosterone has not only effect on blood pressure, but also a deleterious effect on the organ. It still has to be proven, but I think there's good reason to believe it is actually the case because it it docks on not only a dorsal receptor, but also the other other receptors and are not blocked by traditional MRIs. And if you have too much aldosterone in your body, it drives organ damage over time.

第二個原因是醛固酮水平的變化，莎倫之前提到的60%到65%的降低，我認為隨著時間的推移將會帶來巨大的益處，因為醛固酮不僅影響血壓，還會對器官造成損害。雖然這一點還需要進一步證實，但我認為有充分的理由相信它確實有效，因為它不僅與背側受體結合，還與其他受體結合，而且這些受體不會被傳統的核磁共振成像技術阻斷。如果體內醛固酮過多，長期下來會導致器官損傷。

So I think this is going to prove really a big deal. And then you will see the data we have over 24 hours. This is really important because you need to control blood pressure at night in particular, the early morning. Sharon mentioned it. That's when people tend to have cardiovascular events, strokes, MIs. So again, this this long-lasting effect over 24 hours is important. And I can tell you, you won't be disappointed with the blood pressure reduction, you would see. Ruud, anything you want to add in terms of the question about peak sales and the potential for this agent?

所以我認為這將會意義重大。接下來你們會看到我們收集的24小時資料。這一點非常重要，因為尤其需要在夜間和清晨控制血壓。莎倫也提到了這一點。人們往往在清晨發生心血管事件、中風和心肌梗塞。所以，這種持續24小時的長期效果非常重要。我可以告訴你們，血壓降低的效果絕對不會讓你們失望。魯德，關於銷售高峰和這款藥物的潛力，你還有什麼要補充的嗎？

Yes. No, of course. And we are very excited, and hopefully, on Sunday, you will see why. I'm not going to speculate whether it is more than the peak $5 billion peak year sales we've articulated. The only thing I can say, Peter, is that we have, in total, seven studies on this program as we speak. And there are a few studies also in the fixed dose combination with typically flows. And Pascal's alluding to that, Yes, blood pressure in itself is important to control that. But it has a quite devastating effect on the kidney, and we truly believe that the combination of a well-known product like dapagliflozin plus the potential the positive effect of Baxdrostat will be a very substantial driver whether it is $5 billion or perhaps even $10 billion time well sell. But there is an enormous amount of excitement, not only in the company, but more importantly, among physicians for these products. And let's not forget, that's my last remark that a 10-millimeter mercury increases your risk of a MACE event 30%. So I think you will see a renaissance of the treatment of hypertension with a product like Baxdrostat. So very exciting.

是的。當然不是。我們非常興奮，希望週日您就能明白原因。我不會妄加猜測最終銷售額是否會超過我們之前預測的50億美元高峰。彼得，我只能說，目前我們已經完成了七項關於這個計畫的研究。此外，還有一些關於固定劑量組合藥物的研究，這些藥物通常用於治療高血壓。帕斯卡爾也提到了這一點，血壓本身固然重要，但高血壓會對腎臟造成相當大的傷害。我們堅信，像達格列淨這樣知名的產品，加上巴克斯達司他的潛在積極作用，將成為一個非常重要的推動因素，無論最終銷售額是50億美元還是100億美元。不僅公司內部，更重要的是，醫生們對這些產品充滿熱情。最後，別忘了，我還要強調一點：血壓升高10毫米汞柱會使發生主要不良心血管事件（MACE）的風險增加30%。所以我認為，像Baxdrostat這樣的產品將會帶來高血壓治療的復興。這真是令人振奮。

Thank you. And the US political environment, I mean, we've talked a lot about it. And this issue has been long coming in my opinion because -- if you go back 20 years or so, there was limited difference in pricing between the US and Europe. Let's talk about Europe for a second, really. And over time, what has happened is has been a growing difference mostly because in Europe, we've been facing price cut, clawbacks, the whole cottage industry of price reductions and control of access.

謝謝。至於美國的政治環境，我們已經談了很多。在我看來，這個問題由來已久，因為──如果你回顧20年前，美國和歐洲的價格差異很小。我們不妨先談談歐洲。隨著時間的推移，價格差異越來越大，這主要是因為在歐洲，我們面臨降價、追回折扣，以及各種降價和存取控制等一系列問題。

And if you look at health care costs today, well, 20 years ago, I guess, healthcare, 20%, 30%, 15% of care costs were dedicated to pharmaceuticals, innovative pharmaceuticals in particular. Today, you are at 7%, 8%, 9%. And one of the lowest is the U.K. with 7% of healthcare costs dedicated to innovative pharmaceuticals. And you got to ask yourself, I mean, what can you do with 7%, not much. It creates limited room for innovation and innovation that can save lives, but also reduce health care costs by delaying or delaying things like dialysis, saving patients' lives and in cancer, et cetera, et cetera. So, I think there has to be a rebalancing.

如果你看看今天的醫療保健成本，你會發現，20年前，醫療保健成本的20%、30%甚至15%都用於藥品，尤其是創新藥品。而如今，這個比例只有7%、8%、9%。英國是創新藥品投入比例最低的國家之一，僅佔醫療成本的7%。你不得不問自己，區區7%的投入能做什麼？幾乎無能為力。這限制了創新的空間，而創新本來可以挽救生命，也能透過延緩透析等治療來降低醫療成本，進而挽救病患的生命，尤其是在癌症治療等領域。因此，我認為必須重新調整投入比例。

Because the US for the last number of years has been really paying for the cost and the risk associated with innovation. We should never forget the risk. Everybody talks about the cost, but there's a massive risk. I mean, we have a portfolio committee. And very often, we spend several hundred million dollars in one meeting. And if those studies fail, it's a lot of money in the rubbish bin. We've been lucky this year, we've had almost 90% success rate with our Phase III, but it's -- that's not the norm, right? So, people have to realize Innovation is expensive, but it's also very risky.

因為過去幾年，美國一直在為創新帶來的成本和風險付出沉重代價。我們絕不能忘記風險。每個人都在談論成本，但風險也同樣巨大。我的意思是，我們有一個專案組合委員會。很多時候，我們一次會議就要花費數億美元。如果這些研究失敗了，那就意味著一大筆錢打了水漂。今年我們很幸運，三期臨床試驗的成功率接近90%，但這並非普遍現象，對吧？所以，人們必須意識到，創新不僅成本高昂，而且風險也極大。

So I think there has to be a rebalancing, and Europe has to cover a little bit more of this innovation by increasing budgets allocated to innovative pharmaceuticals. And finally, I would say that if you look at innovation, it's happening in the US, very rapidly now it's happening in China, and there's not so much in Europe. So, it would be great for everybody, starting with patients. If Europe was also innovating a lot in our industry, it will also attract investment from companies and drive economic growth.

所以我認為必須進行重新平衡，歐洲需要透過增加創新藥物的預算撥款來更多地支持創新。最後，我想說，如果你觀察創新，你會發現創新主要發生在美國，現在中國也在快速發展，而歐洲的創新力道相對較小。因此，這對所有人都有好處，首先是患者。如果歐洲也能在製藥業大力創新，就能吸引企業投資，進而推動經濟成長。

Now whether we are able to show the benefit of these investments to governments in Europe is still to be seen, but there's clearly benefits to patients, of course, but it also benefits to health care cost as innovation can drive health care costs down -- and there is also economic benefit as the sense sector can drive economic growth like we see in the US, we see now in China. So whether we succeed or not, I don't know, but the danger for Europe is that a lot of these new technologies that we are talking about, they need new capacity, new manufacturing capabilities. And right now, this is going to happen in the US And so, the risk is in 15, 20 years.

現在，我們能否向歐洲各國政府證明這些投資的益處還有待觀察，但顯然，患者會從中受益，醫療保健成本也會降低，因為創新可以降低醫療保健成本——此外，還有經濟效益，因為醫療行業可以像我們在美國和中國看到的那樣，推動經濟成長。所以，我們能否成功，我不得而知，但歐洲面臨的風險在於，我們正在討論的許多新技術都需要新的產能和製造能力。而目前，這種情況將在美國發生。因此，風險可能在未來15到20年內出現。

Europe realized that they have lost control of their supply chain for some of those most important innovative technologies, because they are manufactured in the US and in China. So more to come, and of course, a lot of convincing to try to achieve, but we'll see whether we are able to do that or not. So, we see. I'll move to the next question, Mattias Häggblom at Handelsbanken.

歐洲意識到，他們已經失去了對一些最重要的創新技術供應鏈的控制權，因為這些技術是由美國和中國製造的。所以，未來還會有更多問題出現，當然，我們還需要做很多工作來說服各方，但最終能否成功，我們拭目以待。接下來，我將回答下一個問題，來自漢德爾斯銀行的馬蒂亞斯·哈格布洛姆。

Two questions, please. Firstly on Forxiga, following the validation of the pattern in U.K. and subsequent generic launch, remind me why this loss would not encourage generic companies to explore similar challenges elsewhere in Europe. -- prior to pattern exploration in 2018. And why the situation in the U.K. was unique? And then secondly, for Sharon Mark will present Phase III data for oral PCSK9 inhibitor this weekend once we get the detailed data, what in particular will your team be studying to better understand its clinical profile and how it compares with your own small molecule PCSK9 inhibitor currently in Phase III?

請容許我問兩個問題。首先，關於Forxiga，在英國驗證了其療效模式並隨後推出仿製藥之後，請您提醒我，為什麼這次失敗不會鼓勵仿製藥公司在歐洲其他地區探索類似的挑戰？ ——在2018年進行療效模式探索之前。以及為什麼英國的情況是獨一無二的？其次，Sharon Mark將於本週末公佈口服PCSK9抑制劑的III期臨床試驗數據。一旦我們獲得詳細數據，您的團隊將重點研究哪些方面，以便更好地了解其臨床特徵，以及它與您目前正在進行III期臨床試驗的小分子PCSK9抑制劑相比如何？

And the first one I can quickly cover for -- in the interest of time, but just it's a very specific U.K. law. We can cover the details separately with you if you want offline. But just for everybody's interest, it's a very specific U.K. law that doesn't apply to other countries. And the PCSK9, Sharon, do you want to cover that?

第一個問題我可以快速解答──為了節省時間，我先簡單說說，這是英國一項非常特殊的法律。如果您想了解更多細節，我們可以私下單獨討論。但為了讓大家了解狀況，我先說明一下，這是一項非常特殊的英國法律，不適用於其他國家。莎倫，PCSK9，你想了解嗎？

Sure. I'd love to. So as you know, our own laroprovstat is a true small molecule inhibitor of PCSK9 currently in Phase III. We have shared the Phase II data. They're very encouraging. And we note that because our PCSK9 is a true small molecule, it does not require solubility enhancers, and it doesn't require fasting. And so it offers a target patient profile that we think is very attractive for both monotherapy and combination approaches.

當然可以，我很樂意。如你所知，我們自主研發的拉羅普司他（laroprovstat）是一種真正的小分子PCSK9抑制劑，目前正處於III期臨床試驗階段。我們已經分享了II期臨床試驗的數據，這些數據非常令人鼓舞。值得注意的是，由於我們的PCSK9抑制劑是真正的小分子，因此無需添加增溶劑，也無需空腹服用。因此，它具有非常理想的目標患者群體特徵，我們認為這對單藥治療和聯合治療都極具吸引力。

And in fact, we're exploring combination approaches with a small molecule Lp(a) that is in our portfolio in Phase I, and it also allows us to easily combine with statins, which is standard of care. We were thrilled to see that with combinations, we were able to bring 80% of patients on study to their LDL-C lowering goals. And so we think that we're in a very solid place in the competitive landscape. Now of course, we'll be watching Merck's data to understand how we can continue to meaningfully differentiate ourselves in this landscape as we continue to work on our go-forward plan. We remain very positive about the potential for laroprovstat in this environment. and for the potential to really meaningfully change patients' lives because dyslipidemia is not yet solved. We know the majority of patients aren't reaching their LDL-C lowering goals. And so there's still a major unmet medical need in the marketplace.

事實上，我們正​​在探索將我們產品組合中處於I期臨床試驗階段的小分子Lp(a)與拉羅普司他合併用藥的方案。 Lp(a)還可以輕鬆與他汀類藥物合併使用，而他汀類藥物是目前標準的治療方案。我們很高興地看到，透過聯合用藥，我們能夠幫助80%的受試者達到其LDL-C降低目標。因此，我們認為我們在競爭格局中處於非常有利的地位。當然，我們會密切關注默克公司的數據，以了解如何繼續在這個領域保持顯著的差異化優勢，並繼續推動我們的未來發展計畫。我們對拉羅普司他（laroprovstat）在當前環境下的潛力以及它真正改善患者生活的潛力仍然非常樂觀，因為血脂異常問題尚未得到徹底解決。我們知道大多數患者未能達到其LDL-C降低目標。因此，市場上仍然存在巨大的未滿足醫療需求。

Thank you, Sharon. So we still have quite a number of questions. So, can I suggest that we go one question per person, and we on our side will try to be short in our responses. So the next one is Seamus Fernandez. Over to you, Seamus.

謝謝莎倫。我們還有很多問題。我建議大家每人問一個問題，我們這邊也會盡量簡短回答。下一位是西莫斯·費南德斯。西莫斯，請你提問。

So my one question is on the competitive developments and the evolution of the treatment of asthma and COPD. Just hoping, Ruud, if you could comment on your, I guess, primary competitors outside of Dupixent, but GSK specifically making moves to advance long-acting agents both dupilumab and their potential long-acting CSLP program. Can you just help us with your thoughts specifically on the value of having long-acting agents in that marketplace? And how your own -- whether it be pipeline pursuits or separately, your own existing portfolio is built to defend against that?

所以，我的問題是關於氣喘和慢性阻塞性肺病（COPD）治療領域的競爭格局和發展趨勢。 Ruud，我希望您能談談您的主要競爭對手，除了Dupixent之外，特別是葛蘭素史克（GSK）正在推進長效藥物的研發，包括dupilumab及其潛在的長效CSLP專案。您能否具體談談您對長效藥物在該市場價值的看法？以及貴公司——無論是在研發管線還是現有產品組合——是如何建構自身體系來應對這些競爭的？

Yes. Thank you so much for your question. And let me first emphasize that where we are as a company with both Fasenra and Tezspire is very pleasing. We have for the second quarter -- consecutive quarter sales of above $0.5 billion for Fasenra. So, the product is now annualizing of more than $2 billion a year. And the reason I'm mentioning it is that in all the market research and our own experience in the last few years across all geographies, clearly, efficacy is the number one reason to prescribe products. And I think that's very important in the choice of physicians. Having said that, there's always room for further other modalities. And AstraZeneca is putting a lot of effort in order to generate the first inhaled T-slip molecule, which is quite exciting in order to broaden the patient access for severe uncontrolled asthmatics.

是的，非常感謝您的提問。首先，我想強調的是，我們公司目前在Fasenra和Tezspire兩款產品上的表現都非常令人滿意。 Fasenra第二季的銷售額連續第二季超過5億美元，這意味著該產品的年銷售額已超過20億美元。我之所以提到這一點，是因為在過去幾年我們開展的所有市場調查以及我們在各個地區的實踐經驗中，療效顯然是醫生選擇處方藥的首要原因。我認為這對醫生選擇藥物至關重要。話雖如此，我們始終致力於開發其他治療方式。阿斯特捷利康正在大力研發首個吸入式T-slip分子，這令人振奮，並有望為重度難治性氣喘患者提供更多治療選擇。

We think there's a high unmet medical need. For the simple reason that still too many patients are suffering from severe asthma and are not eligible for injectable. So moving earlier in the treatment paradigm with an inhaled T-slip if it is working, of course, and we will know that in the course of 2026, I think will be a huge advantage for so many patients still suffering. But all in all, it's clear that there are great products. We are in a very good position. We're the market leader in new-to-brand prescriptions, as I mentioned in my prepared remarks, but there's still an enormous opportunity to further accelerate the bio penetration. And last but not least, we are a verge in order to launch Fasenra in China, which is another very important growth driver for us as a company.

我們認為目前存在巨大的未滿足醫療需求。原因很簡單，仍有太多患者有重度氣喘，卻無法接受注射治療。因此，如果吸入式T-slip療法有效（我們將在2026年左右得知其療效），那麼在治療早期階段採用這種療法，對於眾多仍在遭受哮喘折磨的患者來說，無疑是一項巨大的福音。總而言之，我們擁有許多優秀的產品。我們目前處於非常有利的地位。正如我在準備的發言稿中提到的，我們在新藥處方市場處於領先地位，但我們仍有巨大的空間進一步提升生物滲透率。最後，我們即將在中國推出Fasenra，這對我們公司而言是另一個非常重要的成長動力。

The next question is from Matthew Weston at UBS.

下一個問題來自瑞銀集團的馬修‧韋斯頓。

Thank you, Pascal. I think it's probably a question for Dave, but you flagged in your comments that '25 has been or seen a very significant benefit from new patients due to lower Part D co-pays. Of course, that's allowed companies to bring free drug patients into paid coverage. As we think about '26, do we need to consider a significant slowdown in the underlying growth of some of your assets as that free drug warehouse bolus runs out? And if yes, which product should we be most aware of?

謝謝帕斯卡。我覺得這個問題可能應該問戴夫，但你在評論中提到，由於D部分自付額降低，2025年新患者數量顯著增加。當然，這也使得保險公司能夠將原本可以免費用藥的病患納入付費健保範圍。展望2026年，隨著免費用藥的緩衝期結束，我們是否需要考慮貴公司部分資產的潛在成長會大幅放緩？如果需要，我們應該重點關注哪些產品？

Dave, do you want to cover this?

戴夫，你想報道這件事嗎？

Yes, Please. Thanks, Matthew, for the question. So, I think just to take a small step back, if we compare what we'll expect to see in Q2 -- excuse me, Q1 '26 versus '25. First, we'll have a good, if you will, apples-to-apples comparison because both quarters will include the impact of the Part D liability. Secondly, I think also we will continue to see benefit of patients staying on commercial medicine who had switched over this year or were otherwise abandoning. So I think that one of the things that is really important here is that if you take a look at the oral medicines Tagrisso and Calquence in particular, although it's also true of Lynparza.

好的，謝謝。謝謝馬修的提問。那麼，我想先退一步，讓我們比較一下2026年第二季（抱歉，應該是2025年第一季）和2026年第一季的預期情況。首先，這樣比較比較起來就比較公平了，因為這兩個季度都包含了D部分責任的影響。其次，我認為我們也會繼續看到那些今年轉用商業藥品或原本打算放棄商業藥品的患者繼續服用商業藥品所帶來的益處。所以，我認為這裡非常重要的一點是，特別是口服藥物泰瑞沙（Tagrisso）和卡奎斯（Calquence），當然，利帕扎（Lynparza）的情況也類似。

They have fairly long durations of therapy, CLL with treat to progression Tagrisso in terms of the early settings but also indeed what we see with FLAURA2. So, I would expect that patients who've come over to commercial medicine as opposed to being on free drug that we'll continue to see the benefit of those patients and the TRxs come into 2026. The bolus patients who would have been your prevalent pool who came on as the co-pay cap went from the mid-300s down into the 2000s. We may not see that repeat. But I really do think we're going to see demand coming forward from new patients, new indications. And I think that we'll see good oral growth moving forward on our assets.

他們的治療週期相當長，慢性淋巴細胞白血病（CLL）早期階段使用Tagrisso治療直至疾病進展，FLAURA2也證實了這一點。因此，我預計那些從免費藥物轉向商業藥物的患者，我們將繼續看到這些患者受益，並且到2026年，治療方案（TRx）也將繼續有效。曾經，隨著自付費用上限從300多美元降至2,000美元，大量病患湧入市場，他們原本是主要的用藥族群。這種情況可能不會重現。但我確實認為，我們將看到來自新患者和新適應症的需求成長。而且我認為，我們現有的口服藥物產品將實現良好的成長。

Thanks, Dave. Maybe I could add that, a year ago, you may remember a number of people were worried about the impact of the portability on our growth rate. And you can see we've been able to manage that as we said we would, and Dave and his team have been doing an amazing job driving usage and growing our share and growing the volume, to compensate for this part liability that we've had to absorb in 2025. The next question is from Steve Scala at Cowen. Steve, over to you.

謝謝，戴夫。或許我可以補充一點，一年前，你可能還記得，很多人都擔心產品可移植性會影響我們的成長率。正如我們之前承諾的那樣，我們已經成功地應對了這個問題。戴夫和他的團隊在推動產品使用、提升市場份額和擴大銷售方面做得非常出色，足以彌補我們在2025年不得不承擔的部分責任。下一個問題來自Cowen公司的史蒂夫·斯卡拉。史蒂夫，請你提問。

Actually, a question on Calquence. Is the upper end of the peak sales guidance of $3 billion to $5 billion is still achievable given the positive data from competitors Calquence's 2027 IRA negotiated price, which you presumably have by now and IMBRUVICA's IRA negotiated price. And related to all this, was the Calquence IRA price in line with your expectations?

實際上，我有一個關於Calquence的問題。考慮到競爭對手Calquence和IMBRUVICA的2027年IRA（個人退休帳戶）協商價格（您現在應該已經掌握了）的積極數據，30億至50億美元的銷售峰值預期上限是否仍然能夠實現？另外，Calquence的IRA價格是否符合您的預期？

Dave, I think it's for you again.

戴夫，我想這又是給你的。

Steve, thanks for the question. On your last piece, we will share the IRA negotiated price on Calquence once that's public, which will be happening later this quarter. I do want to comment on, though, with respect to your peak year sales question, recall that when we put forth the ambition for 2030 in 2024, we had visibility at that time into the fact that we anticipated that Calquence would be an IP. So that's absolutely consistent with the expectations that we had had. We expected that we would get positive data from AMPLIFY.

史蒂夫，謝謝你的提問。關於你最後提到的問題，我們會在本季稍後公佈Calquence的IRA協商價格，屆時會與大家分享。不過，關於你提到的銷售高峰年，我想補充一點：我們在2024年提出2030年的目標時，就已經預見到Calquence將會是一個智慧財產權。所以，這完全符合我們之前的預期。我們預期會從AMPLIFY計畫中獲得正面的數據。

That's come through and been part of what we've seen. And I think that we've seen really even better than we expected volume growth of Calquence, particularly within the United States. So in terms of the assumptions that went into the projections that we put forth or the ambition that we put forth in 2024, I think it's been positive news, against that and good momentum against those figures. I'm happy that we've seen good share growth in the United States this year on the work that we're doing. We're seeing AMPLIFY in Europe with good initial uptake and look forward to the AMPLIFY opportunity in the US I do want to note that remember that there are no BTK/BCL-2 combinations for finite that are approved in the US in frontline CLL. There's a large number of patients that are receiving a finite treatment that don't involve BTK at all, and we see this as an important opportunity for the asset going forward.

這一點已經得到證實，也是我們所觀察到的結果之一。我認為，Calquence 的銷售成長甚至超出了我們的預期，尤其是在美國市場。因此，就我們先前提出的預測假設以及我們在 2024 年設定的目標而言，我認為目前的業績和成長動能都令人鼓舞。我很高興看到，今年我們在美國取得的市佔率成長得益於我們所做的工作。 AMPLIFY 在歐洲的初期市場表現良好，我們期待它在美國的發展機會。需要指出的是，目前美國尚無核准用於第一線治療 CLL 的 BTK/BCL-2 標靶藥物。大量患者正在接受不涉及 BTK 標靶的治療，我們認為這對該藥物未來的發展是一個重要的機會。

Thanks, Dave. So still lots of growth coming from those approved or soon to be approved indications. And -- we also have escalate in DLBCL that is still to come. Next question is Rajan Sharma Goldman Sachs.

謝謝，戴夫。已獲批准或即將獲準的適應症仍然會帶來很大的成長。此外，我們還有瀰漫性大B細胞淋巴瘤（DLBCL）的升級治療方案即將推出。下一個問題是高盛的拉詹·夏爾馬。

I just wanted to get your thoughts on ENHERTU's trajectory from here, given that we now have the DB09 and the DB11 data and PDUFA next year, which have been seen historically as 2 of the largest opportunities. Some of our KOL feedback has suggested that initial uptake may be a little bit tentative to begin with. So yes, I would just begin to get your thoughts on that. And do you expect those potential approvals during the first half to drive an immediate step-up in ENHERTU's growth in '26 and '27? And then just thinking further out, do you think you'll be reaching peak penetration in breast cancer as you approach your 2030 target?

我想了解您對ENHERTU未來發展軌蹟的看法，因為我們現在有了DB09和DB11的數據，而且明年還將有PDUFA審批，這兩項歷來被視為最大的機會。我們的一些關鍵意見領袖回饋說，初期市場接受度可能會比較謹慎。所以，我想聽聽您對此的看法。您是否預計上半年這些潛在的審批會立即推動ENHERTU在2026年和2027年成長？再展望未來，您認為在接近2030年目標時，ENHERTU在乳癌領域的市場滲透率會達到高峰嗎？

Thank you. So question with switch up, David, go ahead.

謝謝。那麼，關於“Switch Up”的問題，David，請繼續。

All right. We'll do. So first of all, I think as we take a look at 09 and the combination of both 05 and 11, let's take those in two separate parts. DESTINY-Breast09 is clearly a very important opportunity to move ENHERTU from the later line metastatic setting or the second-line plus metastatic setting that we're in today into a frontline setting. The reason that, that is important is, first and foremost, many more patients will have the opportunity to benefit from an ENHERTU because unfortunately, the number of patients that are able to receive a second-line therapy goes down just as patients unfortunately either pass away or they're unable to receive further treatment.

好的，我們會的。首先，我認為在分析 DESTINY-Breast09 研究以及 DESTINY-Breast05 和 DESTINY-Breast01 的共同研究時，我們應該分成兩部分來討論。 DESTINY-Breast09 研究顯然是一個非常重要的機會，可以將 ENHERTU 從目前用於轉移性乳癌的後期治療或第二線及以上治療方案，推廣到第一線治療。之所以如此重要，首先也是最重要的是，更多的患者將有機會受益於 ENHERTU 治療。不幸的是，隨著患者不幸去世或無法繼續接受治療，能夠接受二線治療的患者數量正在減少。

So opening up that population is going to be really important. Secondly, the duration of therapies that we see because of the long PFSs within DB09 are really important. And that's as a result of this treat to progression new paradigm that's being established. And I think that on this, it's important to note that one of the things that's been really well received by the clinical community is the lack of cumulative toxicity that is associated with ENHERTU and what we're seeing within these studies.

因此，擴大適用人群至關重要。其次，DB09研究中觀察到的較長無惡化存活期（PFS）也意味著治療持續時間的延長，這一點非常重要。這得歸功於正在建立的「治療至疾病進展」的新範式。我認為，值得注意的是，ENHERTU療法及其相關研究中觀察到的累積毒性較低，這一點受到了臨床界的廣泛好評。

That cumulative toxicity is in large part why there's been discontinuation of the taxanes in some of the other metastatic settings. And so, we're really looking for this to be an opportunity to make sure that we're driving to the way that DB09 was designed, which is treat to progression. DB05 and DB11 in early stage, they represent a blockbuster opportunity together. This is a great opportunity to bring ENHERTU into early settings. And I think that in terms of when will we expect uptake, certainly, the clinical community does follow guidelines. DB09, we anticipate coming into guidelines sometime soon, we would hope -- remember that the New England Journal of Medicine publication just came through just very, very recently. And we'll obviously look forward to making sure that the progress that we've made on the early studies gets published as well.

累積毒性是紫杉烷類藥物在其他一些轉移性疾病治療中停用的主要原因之一。因此，我們非常希望藉此機會，確保我們能夠按照DB09的設計理念，即「治療至疾病進展」的方式進行治療。 DB05和DB11處於早期階段，它們共同代表著一個重磅炸彈級的治療機會。這是一個將ENHERTU應用於早期治療的絕佳機會。至於何時能夠被廣泛應用，我認為臨床界肯定會遵循指引。我們預計DB09很快就能被納入指南，我們希望──別忘了，《新英格蘭醫學雜誌》上的文章也是最近才發表的。我們當然也期待確保我們在早期研究中取得的進展能夠盡快發表。

So we'll try the last four questions and the time that remains. Let's go with one question per person and be short in our responses. Luisa at Berenberg. Over to you.

所以我們試試剩下的四個問題，利用剩下的時間。每人一個問題，回答要簡短。貝倫貝格銀行的露易莎，請你回答。

Thank you, Pascal. I wanted to return to the 2030 ambition because you've talked about and we've seen there's unprecedented success rate this year. So is the $80 billion now conservative? Can you comment at all on the mix that you're seeing with the success and what that means for profitability? And although the ex US, you're sticking at 50% ex US contribution, are there any changes in timing of launches or the mix of the ex US in light of that US deal? .

謝謝你，帕斯卡爾。我想再談談2030年的目標，因為你之前提到過，我們也看到了今年的成功率空前高漲。那麼，現在800億美元的目標是否有保守估計呢？你能否就目前所取得的成功以及這些成功背後的構成和獲利能力發表一些看法？雖然你仍然堅持美國以外地區貢獻50%的目標，但考慮到與美國的協議，產品發佈時間或美國以外地區的組成是否會有任何變化？

Thank you, Luisa. Not long ago, people were thinking the $80 billion was not achievable. Now it's going to be a soft goal. It remains an ambitious goal. And of course, we are very excited with all this new positive readouts. But it's a risky business. That's what I said not long a few minutes ago. So, we have to remain cautious with the readouts that are coming next year. We don't know. I hope to go. We continue to have a high positive success readout in our readouts, but we can't be sure. So let's stick to the $80 billion. It's an ambitious goal.

謝謝你，路易莎。不久前，人們還認為800億美元的目標無法達成。現在，這已經是一個比較容易達成的目標了。當然，它仍然是一個雄心勃勃的目標。我們對所有這些新的正面數據感到非常興奮。但這畢竟是一項風險很大的業務。我剛才也說過。所以，我們必須對明年即將公佈的數據保持謹慎。我們無法確定。我希望能夠實現。我們的數據持續顯示出很高的成功率，但我們無法完全確定。所以，讓我們堅持800億美元的目標。這是一個雄心勃勃的目標。

And if we can overachieve of course, we'll do our very best to overachieve. Now in the second question with the profitability, we want to be a growth company until 2030, but also beyond 2030. So certainly, we can assume -- we can assume profitability increases, but you also have to understand we will want to continue investing in R&D. We have tremendous technologies in our hands, cell therapy, T cell engagers, radioligands, which we haven't talked about today, all of those are making good progress. So, we certainly would want to invest in those from an R&D perspective, but also from a commercial perspective and beyond oncology, we have a lot to do also in biopharma in rare disease. So, we're not going to commit to any profitability target or improvement beyond what we've already said in the past. Aradhana, anything you wanted to add to this?

當然，如果我們能超額完成目標，我們一定會盡全力去實現。關於第二個問題，也就是獲利能力，我們希望在2030年之前以及之後都保持成長。所以，我們當然可以預期獲利能力會提高，但您也必須明白，我們會繼續投資研發。我們掌握著許多強大的技術，例如細胞療法、T細胞銜接器、放射性配體（我們今天沒有談到這些），所有這些技術都取得了良好的進展。因此，我們當然會從研發的角度投資這些技術，同時也會從商業角度進行投資。除了腫瘤學領域，我們在罕見疾病生物製藥領域也有很多工作要做。所以，我們不會承諾任何超出我們先前所述範圍的獲利目標或改善措施。 Aradhana，您還有什麼要補充的嗎？

No, not at all. (inaudible)

不，完全不是。 （聽不清楚）

So the next question is from Gonzalo Artiach at Danske Bank.

下一個問題來自丹麥銀行的 Gonzalo Artiach。

Gonzalo Artiach at Danske Bank. I have one for Marc on gefurulimab and the data has been recently presented. It seems that the efficacy and safety signals have come fairly in line with Ultomiris in MG. How should we understand the dynamics between these two products in MG? And also I wanted to ask if you have any plans ahead for gefurulimab in other indications where Ultomiris is now approved. Thank you very much.

我是丹麥銀行的 Gonzalo Artiach。我有一個關於格夫魯利單抗（gefurulimab）的問題想請教Marc，相關數據最近已經公佈。數據顯示，格夫魯利單抗在治療重症肌無力（MG）的療效和安全性與優思明（Ultomiris）基本一致。我們該如何理解這兩種藥物在重症肌無力治療中的動態變化？另外，我還想問一下，您未來是否有計劃將格夫魯利單抗應用於優思明已獲批的其他適應症？非常感謝。

First of all, thank you very much for the question on the rare disease. So if you remember what the trial of gefurulimab was done in patients earlier than the trials we have done historically with Ultomiris. You will remember that Alexion was a pioneer company to obtained the first approval with modern medicine in myasthenia gravis. And subsequently, we -- after Soliris, we developed Ultomiris and now we go one step earlier. The other important factor of gefurulimab is a mode of administration, a subcut weekly provided in either prefilled syringe or an auto-injector that can be injected in 15 seconds. So it's a very patient convenient, patient easy type of administration and the speed of onset has been demonstrated in the study and also the sustainability is as good as it was for Ultomiris. So that's what I can say about gefurulimab.

首先，非常感謝您提出關於罕見疾病的問題。如果您還記得，我們​​之前在患者身上進行的格夫魯利單抗（gefurulimab）試驗比我們之前進行的優托米瑞（Ultomiris）試驗更早。您應該記得，Alexion是率先獲得現代醫學在重症肌無力治療領域批准的先驅公司。隨後，在Soliris之後，我們開發了優托米瑞，現在我們更進一步。格夫魯利單抗的另一個重要優點是其給藥方式，每週一次皮下注射，可透過預充式註射器或自動注射器給藥，只需15秒即可完成註射。這種給藥方式非常方便患者，研究已證實其起效迅速，療效持久性也與優托米瑞一樣好。以上就是我對格夫魯利單抗的介紹。

Thank you, Marc. And the last question is from Simon Baker at Redburn. Over to you, Simon.

謝謝你，馬克。最後一個問題來自雷德伯恩的西蒙貝克。西蒙，請你提問。

Just changing the subject is. I think we don't ask many questions on. But one for Susan, could you give us an update on your confidence in sone vedotin as we come up to the gastric Phase III data in H1 '26? And also some thoughts on the broader scope of Claudin18 beyond gastric?

換個話題吧。我覺得我們很少問這類問題。不過蘇珊，我有個問題想請教您，隨著2026年上半年胃部III期臨床試驗數據的公佈，您對Sone Vedotin的信心有何更新？另外，您能否談談Claudin18在胃部以外的更廣泛應用前景？

Thanks for the question. So, sone vedotin is a Claudin18.2 ADC with an MMAE tubulin-based payload. And we've seen encouraging response rate data in late-line patient populations. We are investigating this versus current standard of care, but we're also looking within the potential to take it into earlier line settings, including in combinations. And have seen of course, that there are exciting opportunities for MMAE-based ADCs in combination with IO therapy. So, that represents a significant opportunity to sone v. Claudin18.2 is expressed in a high proportion of gastric cancer more than 50% of patients.

感謝您的提問。 Sone Vedotin 是一種靶向 Claudin18.2 的抗體偶聯藥物 (ADC)，其有效載荷基於 MMAE 微管蛋白。我們在晚期患者群體中觀察到了令人鼓舞的緩解率數據。我們正在研究它與目前標準療法的比較，同時也在探索將其應用於早期治療（包括聯合治療）的潛力。當然，我們也看到基於 MMAE 的 ADC 與免疫療法聯合應用具有令人振奮的前景。因此，這代表著 Sone Vedotin 的一個重要發展機會。 Claudin18.2 在胃癌患者中高表達，超過 50% 的患者表達 Claudin18.2。

So it's a much bigger opportunity than the HER2 high group, if you want to compare with what we've seen with HER2. And I think it's also expressed in pancreatic cancer. And we are looking at the data in pancreatic cancer as well. I mean, of course, there, the bar is high. So, what we've done is go forward with the gastric cancer opportunity first, and we'll continue to explore the opportunity for this and also a topo-based ADC with a Claudin18.2 targeting also in pancreatic cancer, just to see which payload works best.

所以，如果我們要和HER2高表達組進行比較，就會發現它比HER2高表達組的機會大得多。而且我認為它在胰臟癌中也有表現。我們也在研究胰臟癌的數據。當然，胰臟癌的門檻很高。因此，我們首先推進了胃癌的治療，並將繼續探索其治療機會，以及一種針對Claudin18.2的拓樸異構酶抗體偶聯藥物（ADC）在胰臟癌中的應用，以確定哪種有效載荷效果最佳。

Thank you, Susan. So in closing, maybe a few words back to Luisa's question. I realized I didn't totally answer Luisa's question. As the pipeline develops, you can see we'll have a lot of Specialty Care products moving forward. And of course, those tend to drive higher profitability as we know. But we also have products that will address conditions like weight loss, metabolic conditions, metabolic disease and those, of course, require more investment. So, I think overall, you can suddenly assume improvement of profitability from a commercial viewpoint.

謝謝蘇珊。最後，我想再補充幾句關於路易莎的問題。我意識到我並沒有完全回答路易莎的問題。隨著產品線的推進，我們未來將會推出許多特效護理產品。當然，我們都知道，這些產品往往能帶來更高的利潤。但我們也有一些產品可以解決諸如減肥、代謝性疾病等問題，這些產品自然需要更多的投資。所以，我認為從商業角度來看，整體而言，我們可以預期獲利能力會有所提升。

The R&D, we want to continue spending at the -- in the low 20s, as we've done in the past. But as I said before, we will not commit to any any direction of the action of travel of our profitability because we need to see how the pipeline develops, and that's what we've said in the past. And more frankly, we've been good and lucky. We have had a very high success rate, and I hope it continues. And if it does, then we have to support all these products. So with this, thank you so much for your great questions and your interest, and I wish you a good rest of the day.

研發方面，我們希望繼續維持20美元左右的投入，就像我們過去所做的那樣。但正如我之前所說，我們不會承諾任何關於獲利方向的具體措施，因為我們需要觀察產品線的發展情況，這也是我們過去一直在強調的。坦白說，我們一直很幸運，也進展順利。我們的成功率非常高，我希望這種勢頭能夠持續下去。如果能夠維持下去，我們就必須為所有這些產品提供支援。最後，非常感謝大家提出的精彩問題和關注，祝福大家今天剩下的時間愉快。