AstraZeneca PLC (AZN) 2023 Q1 法說會逐字稿

Good morning to those joining from the U.K. and the U.S. Good afternoon to those in Central Europe, and good evening to those listening in Asia. Welcome, ladies and gentlemen, to AstraZeneca's Q1 2023 Results Webinar for investors and analysts.

早上好，來自英國和美國的聽眾。下午好，中歐的聽眾，晚上好，亞洲的聽眾。女士們，先生們，歡迎參加阿斯利康 (AstraZeneca) 為投資者和分析師舉辦的 2023 年第一季度業績網絡研討會。

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. 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 also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation. (Operator Instructions).

在我移交給阿斯利康之前，我想閱讀安全港聲明。公司打算利用 1995 年美國私人證券訴訟改革法案的安全港條款。本次電話會議的參與者可以就阿斯利康的運營和財務業績做出前瞻性陳述。儘管我們認為我們的預期是基於合理的假設，但就其本質而言，前瞻性陳述涉及風險和不確定性，並且可能受到可能導致實際結果與這些前瞻性陳述所表達或暗示的結果存在重大差異的因素的影響。在本次電話會議上做出的任何前瞻性陳述都反映了本次電話會議時可獲得的知識和信息。公司不承擔更新前瞻性陳述的義務。另請仔細閱讀本演示文稿附帶的幻燈片中的前瞻性聲明免責聲明。 （操作員說明）。

And with that, I will now hand you over to the company.

那麼，我現在將把你交給公司。

Thank you, operator, and good afternoon, everyone. It's Andy Barnett, Head of Investor Relations at AstraZeneca, and I'm very pleased to welcome you to AstraZeneca's First Quarter 2023 Conference Call. As usual, all materials presented are available on our website.

謝謝接線員，大家下午好。我是阿斯利康投資者關係主管 Andy Barnett，我很高興歡迎您參加阿斯利康 2023 年第一季度電話會議。與往常一樣，所有展示的材料都可以在我們的網站上找到。

This slide contains our usual safe harbor statement. We will be making comments on our performance using constant exchange rates, or CER, core financial numbers and other non-GAAP measures. A GAAP -- a non-GAAP to GAAP reconciliation is contained within the results announcement, numbers today are in millions of U.S. dollars unless otherwise stated.

這張幻燈片包含我們通常的安全港聲明。我們將使用固定匯率或 CER、核心財務數據和其他非 GAAP 指標對我們的業績發表評論。 GAAP——非 GAAP 與 GAAP 對賬包含在業績公告中，除非另有說明，今天的數字以百萬美元為單位。

This slide shows our agenda for today's call. Following prepared remarks, we will open the line up for questions. We will try and address as many questions as we can during the allotted time. Although I would ask that participants limit the number of questions you asked to allow others a fair chance to participate in the Q&A. (Operator Instructions)

這張幻燈片顯示了我們今天電話會議的議程。在準備好的評論之後，我們將開始提問。我們將在規定的時間內嘗試解決盡可能多的問題。儘管我會要求參與者限制您提出的問題的數量，以便讓其他人有公平的機會參與問答。 （操作員說明）

With that, Pascal, over to you.

有了這個，帕斯卡，交給你了。

Thank you, Andrew, and hello, everyone. Please advance to Slide 5. We delivered total revenue of $10.9 billion in the first quarter, which was stable compared to the prior year. This performance is really quite remarkable when you consider that a 15% growth in revenue from our ex COVID medicines offset the decline in revenue from our COVID-19 medicines of $1.5 billion in the quarter. Core earnings per share grew 6% compared to the first quarter of 2022. This growth reflects both the decline in COVID-19 medicine revenues as well as important investments we are making in our business to advance our pipeline and deliver on the full promise of our recently launched medicines. Based on our strong fundamentals and outlook for the year, we are reiterating our 2023 guidance. Please move to the next slide.

謝謝你，安德魯，大家好。請轉到幻燈片 5。我們第一季度的總收入為 109 億美元，與去年同期相比保持穩定。當您考慮到我們前 COVID 藥物收入增長 15% 抵消了本季度 COVID-19 藥物收入下降 15 億美元時，這一表現確實非常了不起。與 2022 年第一季度相比，每股核心收益增長了 6%。這一增長既反映了 COVID-19 藥品收入的下降，也反映了我們為推進我們的產品線和兌現我們的全部承諾而對我們的業務進行的重要投資最近推出的藥物。基於我們強勁的基本面和今年的展望，我們重申了 2023 年的指導方針。請移至下一張幻燈片。

Excluding our COVID-19 medicines and in addition to our broad base of growth across these areas, we delivered strong growth across all regions. Importantly, in the emerging markets, our ex-COVID-19 medicine grew by 22%. In China, we have now seen 3 successive quarters of growth as we continue to launch innovative medicines and growth outpaces anticipated declines in some of our older medicines. This growth is a clear reflection of the value of our broad portfolio and our sustained focus on emerging markets over time. Our business is highly resilient with pipeline momentum accelerating as a result of both internal and external innovation. Please move to Slide 7.

不包括我們的 COVID-19 藥物，除了我們在這些領域的廣泛增長基礎外，我們在所有地區都實現了強勁增長。重要的是，在新興市場，我們的前 COVID-19 藥物增長了 22%。在中國，隨著我們繼續推出創新藥物，我們已經連續三個季度實現增長，並且增長速度超過了我們一些老藥的預期下降。這種增長清楚地反映了我們廣泛的投資組合的價值以及我們長期以來對新興市場的持續關注。我們的業務具有高度的彈性，由於內部和外部創新，管道勢頭正在加速。請移至幻燈片 7。

One illustration of this momentum is our focus on initiating 30 Phase III trials in 2023. I'm pleased to announce we have already dosed patients in 6 new Phase III trials since the start of the year. This includes 2 trials of Dato-DXd in combination with IO medicines, reflecting our confidence in the promise of these regimens to enhance outcomes for patients with lung cancer.

這種勢頭的一個例證是我們專注於在 2023 年啟動 30 項 III 期試驗。我很高興地宣布，自今年年初以來，我們已經在 6 項新的 III 期試驗中對患者進行了給藥。這包括 2 項 Dato-DXd 聯合 IO 藥物的試驗，反映出我們對這些治療方案改善肺癌患者預後的承諾充滿信心。

Given that inflammatory cells play a key role in the eosinophilic esophagitis and with (inaudible) at the top of the inflammatory cascade, we've initiated the crossing trial for Tezspire, (inaudible) in EoE. SUPERNOVA is a trial of our novel antibody, AZD3152 for the prophylactic treatment of COVID-19 with potential approval in the second half of this year. Here, our aim is to protect people who don't want an effective immune response to vaccination, which represents about 2% of the population.

鑑於炎症細胞在嗜酸性粒細胞性食管炎中起著關鍵作用，並且（聽不清）處於炎症級聯反應的頂端，我們已經在 EoE 中啟動了 Tezspire（聽不清）的交叉試驗。 SUPERNOVA 是我們的新型抗體 AZD3152 的試驗，用於 COVID-19 的預防性治療，並可能在今年下半年獲得批准。在這裡，我們的目標是保護那些不希望對疫苗接種產生有效免疫反應的人，這些人約佔人口的 2%。

CAMBRIA-1 is our first trial investigating camizestrant, our next-generation oral serve in the adjuvant breast cancer setting, where there is significant opportunity to improve long-term outcomes. Finally, we initiated a trial of Ultomiris for the prevention of acute kidney injury associated with cardiac surgery. This represents an area of high unmet need with currently no approved therapies. Acute kidney injury can occur and above -- up to 20% of patients undergoing cardiac surgery, but the risk increases to over 60% in patients with chronic kidney disease. The ARTEMIS trial focuses on those patients with kidney ischemia where complement plays a key role. While we plan to provide an update each quarter on our new Phase III trial start, we expect the majority to those in the second half of this year.

CAMBRIA-1 是我們的第一項研究 camistrant 的試驗，camistrant 是我們在乳腺癌輔助治療中的下一代口服藥物，它有很大的機會改善長期結果。最後，我們啟動了一項 Ultomiris 試驗，用於預防與心臟手術相關的急性腎損傷。這代表了一個高度未滿足需求的領域，目前尚無批准的療法。急性腎損傷可能發生及以上——接受心臟手術的患者高達 20%，但慢性腎病患者的風險增加到 60% 以上。 ARTEMIS 試驗的重點是補體發揮關鍵作用的腎缺血患者。雖然我們計劃每個季度提供有關我們新的 III 期試驗開始的更新，但我們預計今年下半年的大部分更新。

Now please turn to Slide 8, and Aradhana can take you through our financial highlights in the quarter as well as provide some insights into how we are fully embracing artificial intelligence and machine learning across our business. Over to you, Aradhana.

現在請轉到幻燈片 8，Aradhana 可以帶您了解我們本季度的財務亮點，並就我們如何在我們的業務中全面採用人工智能和機器學習提供一些見解。交給你了，Aradhana。

Thank you, Pascal, and good afternoon, everyone. As usual, I will start with our reported P&L.

謝謝 Pascal，大家下午好。像往常一樣，我將從我們報告的損益開始。

Please turn to Slide 9. Total revenue in the first quarter was stable compared to the prior year. Recall that Q1 of last year benefited from around $1.6 billion in COVID-19 medicine sales, which have declined as anticipated by 89% to $155 million. Excluding COVID-19 medicines, total revenue increased by 15% in the first quarter.

請翻到幻燈片 9。第一季度的總收入與去年同期相比穩定。回想一下，去年第一季度受益於約 16 億美元的 COVID-19 藥品銷售額，如預期的那樣下降了 89% 至 1.55 億美元。不包括 COVID-19 藥物，第一季度總收入增長了 15%。

In an effort to increase transparency, starting in Q1, we will break out recurring revenues from partnered products into separate line called Alliance revenue. This line will include royalties and profit shares from partnered medicines, such as Enhertu and Tezspire in geographies where our partner books product sales. Upfront and milestone payments will continue to be reported as collaboration revenue. Hopefully, this results in improved visibility to revenue from partner medicines.

為了提高透明度，從第一季度開始，我們將把來自合作產品的經常性收入分成單獨的一條線，稱為聯盟收入。這條線將包括來自合作藥品的特許權使用費和利潤分成，例如在我們的合作夥伴預訂產品銷售的地區的 Enhertu 和 Tezspire。預付款和里程碑付款將繼續作為協作收入報告。希望這能提高合作藥物收入的可見性。

Finally, we saw some relatively large core adjustments last year as a result of the unwind of the Alexion fair value inventory uplift. However, we only had $36 million of this in the quarter, and it will be minimal in the future. Please turn to the next slide, which depicts our core P&L.

最後，由於 Alexion 公允價值庫存提升的解除，我們去年看到了一些相對較大的核心調整。但是，我們在本季度只有 3600 萬美元，而且將來會很少。請轉到下一張幻燈片，它描述了我們的核心損益表。

Our core gross margin in the first quarter was 83.3%, an increase of 4 percentage points compared to the prior period, which was negatively impacted by higher COVID-19 sales. Q1 2023 core gross margin also benefited from product mix and lower production cost from prior quarters. On a full year basis, we still anticipate a slight improvement in gross margins compared to pre-pandemic levels. This is driven by lower COVID-19 revenue, higher oncology and Alexion sales, but impacted by increasing contribution from partnered medicines and higher costs relating to inflation.

我們第一季度的核心毛利率為 83.3%，比上一季度增長 4 個百分點，這是受到 COVID-19 銷售額增加的負面影響。 2023 年第一季度的核心毛利率也受益於產品組合和比前幾個季度更低的生產成本。從全年來看，與大流行前的水平相比，我們仍然預計毛利率將略有改善。這是由較低的 COVID-19 收入、較高的腫瘤學和 Alexion 銷售額推動的，但受到合作藥物貢獻增加和與通貨膨脹相關的較高成本的影響。

In the second half of the year, we expect the usual seasonal impact from FluMist as well as incremental costs relating to the production of our new COVID-19 antibody is at AZD3152.

在今年下半年，我們預計 FluMist 通常的季節性影響以及與我們新的 COVID-19抗體生產相關的增量成本為 AZD3152。

Core operating expenses increased by 9% in the quarter. However, this was partly due to lower cost in the prior year period. As Pascal mentioned, we started 6 new trials in year-to-date, and we anticipated starting 30 during the full year, which will affect quarterly R&D cost phasing with R&D expenses in subsequent quarters expected to be higher than in Q1.

本季度核心運營費用增長了 9%。然而，這部分是由於去年同期的成本較低。正如 Pascal 提到的，我們今年迄今開始了 6 項新試驗，我們預計全年將啟動 30 項，這將影響季度研發成本分期，後續季度的研發費用預計將高於第一季度。

On the SG&A side, we continue to invest behind our launches, including new indications for Imfinzi and Enhertu and our respiratory portfolio.

在 SG&A 方面，我們繼續投資於我們的發布，包括 Imfinzi 和 Enhertu 的新適應症以及我們的呼吸產品組合。

On a full year basis, we still expect core operating expenses to increase by low to mid-single-digit percentage, but there will be quarter-on-quarter variability Other operating income of $379 million in the quarter includes a gain from the divestment of Pulmicort FlexHaler in the U.S. on top of some background level of other operating income from historical divestments. Taking these elements together, core EPS increased by 6% at constant exchange rate to $1.92 in the quarter.

從全年來看，我們仍然預計核心運營費用將以中低個位數的百分比增長，但季度環比會有變化 本季度其他運營收入 3.79 億美元，包括剝離美國的 Pulmicort FlexHaler 在歷史撤資的其他營業收入的一些背景水平之上。綜合這些因素，本季度核心每股收益按固定匯率計算增長 6% 至 1.92 美元。

Earlier this month, we announced the simplification of the agreement with Sobi and Sanofi on Nirsevimab. This will simplify our P&L and result in us recognizing $718 million of other operating income in the second quarter following the release of the liability on our balance sheet much of which had been expensed through our core P&L. Now please turn to Slide 11.

本月早些時候，我們宣布簡化與 Sobi 和賽諾菲就 Nirsevimab 達成的協議。這將簡化我們的損益表，並導致我們在資產負債表上釋放負債後的第二季度確認 7.18 億美元的其他營業收入，其中大部分已通過我們的核心損益表支出。現在請轉到幻燈片 11。

Our cash flow from operating activities of $3.1 billion was stable in the quarter despite the significant decline in COVID-19 revenue. We continue to work on improving cash conversion and have already made significant progress on that journey. Net debt increased by $2.1 billion to $25.1 billion, driven by the second interim dividend payment of around $3 billion and approximately $2 billion in deal payments, including a second payment of around $900 million to Acerta shareholders and roughly $800 million for the recent SynCor acquisition.

儘管 COVID-19 收入大幅下降，但本季度我們來自經營活動的現金流量為 31 億美元，保持穩定。我們繼續致力於改善現金轉換，並且已經在這一過程中取得了重大進展。受第二次中期股息支付約 30 億美元和約 20 億美元交易支付的推動，淨債務增加 21 億美元至 251 億美元，其中包括向 Acerta 股東支付約 9 億美元的第二筆款項以及為最近的 SynCor 收購支付約 8 億美元。

For the full year, we still expect deal payments tied to prior business development transactions to be at a similar level as last year. Our current net debt-to-EBITDA ratio is 2.3x or 1.9 if adjusting for the Alexion fair value uplift.

對於全年，我們仍預計與先前業務開發交易相關的交易付款將與去年持平。如果根據 Alexion 的公允價值提升進行調整，我們目前的淨債務與 EBITDA 比率為 2.3 倍或 1.9。

As Pascal stated earlier, our guidance for the full year remains unchanged. We continue to anticipate total revenue, excluding COVID-19 to increase by low double-digit percentage. Including COVID-19 medicines, we anticipate total revenue to increase by low to mid-single-digit percentage. Core EPS is anticipated to increase by high single-digit to low double-digit percentage. Based on average March FX rates, we anticipate a low single-digit adverse FX impact on both total revenue and core EPS. Please turn to Slide 12.

正如 Pascal 之前所說，我們對全年的指導保持不變。我們繼續預計不包括 COVID-19 在內的總收入將以低兩位數的百分比增長。包括 COVID-19 藥物在內，我們預計總收入將以中低個位數百分比增長。預計核心每股收益將以高個位數百分比增長至低兩位數百分比。根據 3 月份的平均匯率，我們預計總收入和核心每股收益將受到低個位數的不利外匯影響。請轉到幻燈片 12。

As a company that thrives on innovation, we are constantly evolving our ways of working and have embedded AI broadly across the organization. Over the course of this year, we plan to update you with some real-world examples each quarter on how this has helped us to improve productivity and drive innovation. This will help you to understand why we're making significant investments in this area. First, we'll focus on R&D, where we have over 400 data scientists employed and over 100 active AI projects underway. Later in his prepared remarks, many will provide examples of AI and drug discovery.

作為一家以創新為生的公司，我們不斷改進我們的工作方式，並在整個組織中廣泛嵌入人工智能。在今年的過程中，我們計劃每個季度向您更新一些真實世界的例子，說明這如何幫助我們提高生產力和推動創新。這將幫助您理解我們為什麼要在這個領域進行大量投資。首先，我們將專注於研發，我們僱用了 400 多名數據科學家，並且正在進行 100 多個活躍的 AI 項目。稍後在他準備好的發言中，許多人將提供人工智能和藥物發現的例子。

With that, please turn to Slide 13, and I will hand over to Dave to take you through our oncology business performance.

有了這個，請轉到幻燈片 13，我將交給 Dave 向您介紹我們的腫瘤業務績效。

Thank you, Aradhana. Slide 14, please. Oncology delivered a solid performance in the first quarter with total revenues of over $4 billion, up 19% versus 2022. We saw double-digit product sales growth across the U.S., Europe, emerging markets and established Rest of world driven by new indication launches and continued demand generation.

謝謝你，阿拉達納。請放幻燈片 14。腫瘤學在第一季度表現穩健，總收入超過 40 億美元，比 2022 年增長 19%。我們看到美國、歐洲、新興市場和成熟市場的產品銷售額實現兩位數增長，這得益於新適應症的推出和持續的需求產生。

Now turning to our individual medicines. Tagrisso Global revenues grew by 15% in the quarter. In the U.S., we saw sustained demand in both ADAURA and FLAURA, coupled with improved duration of therapy and FLAURA. In Europe, growth of 8% was offset by pricing clawbacks in certain markets. Tagrisso performance in China was strong, recovering as expected following fourth quarter hospital budget management dynamics resulting in first quarter growth of 17% in emerging markets. Lynparza, the leading PARP inhibitor globally delivered first quarter product sales growth of 10%. The U.S. was impacted by destocking following an inventory build in the fourth quarter in anticipation of the PROpel approval.

現在轉向我們的個別藥物。 Tagrisso Global 的收入在本季度增長了 15%。在美國，我們看到 ADAURA 和 FLAURA 的持續需求，以及治療持續時間和 FLAURA 的改善。在歐洲，8% 的增長被某些市場的定價回扣所抵消。 Tagrisso 在中國的表現強勁，在第四季度醫院預算管理動態導致新興市場第一季度增長 17% 後恢復如預期。全球領先的 PARP 抑製劑 Lynparza 第一季度的產品銷售額增長了 10%。由於預期 PROpel 獲得批准，美國在第四季度庫存增加後受到去庫存的影響。

While there are opportunities for continued demand expansion in the U.S., these growth areas are more challenging. Specifically, we continue to work on improving HRD testing rates in ovarian as well as BRCA testing and prescribing rates and hormone receptor positive breast cancer. Outside the U.S., we're encouraged by Lynparza growth in Europe of 18%, including strong launch trajectory for PROpel in Germany.

雖然美國有持續需求擴張的機會，但這些增長領域更具挑戰性。具體來說，我們繼續致力於提高卵巢的 HRD 檢測率以及 BRCA 檢測和處方率以及激素受體陽性乳腺癌。在美國以外，我們對 Lynparza 在歐洲增長 18% 感到鼓舞，其中包括 PROpel 在德國的強勁上市軌跡。

Turning now to Imfinzi. Total revenues inclusive of Imjudo grew an impressive 56% fueled by new launches. This performance was driven by 66% growth in the U.S. with strong uptake across new indications, particularly TOPAZ-1 and HIMALAYA. And in Europe and Japan, early launch momentum from TOPAZ-1 has been encouraging. Calquence's total revenues increased 31% year-on-year, supported by ex U.S. demand growth. As expected, U.S. performance in the first quarter was impacted by destocking following maleate tablet approval in the third quarter of last year. Looking at new starts in TRx share in the frontline CLL setting, Calquence remains the clear standard of care in the face of increasing class competition. That said, we do see some impact on new share in both the relapsed/refractory and frontline settings.

現在轉向 Imfinzi。在新產品發布的推動下，包括 Imjudo 在內的總收入增長了 56%，令人印象深刻。這一業績得益於美國 66% 的增長以及對新適應症（尤其是 TOPAZ-1 和 HIMALAYA）的強勁吸收。在歐洲和日本，TOPAZ-1 的早期發射勢頭令人鼓舞。在美國以外需求增長的支持下，Calquence 的總收入同比增長 31%。正如預期的那樣，美國第一季度的業績受到去年第三季度馬來酸鹽片劑批准後去庫存的影響。縱觀一線 CLL 環境中 TRx 份額的新開端，面對日益激烈的階級競爭，Calquence 仍然是明確的護理標準。也就是說，我們確實看到了對複發/難治性和前線設置中新份額的一些影響。

Turning now to Enhertu. Total revenue was up 203% in the first quarter to $257 million. In the U.S. Enhertu new patient share is now approximately 50% across both second-line HER2-positive and hormone receptor positive HER2 low, post-chemo metastatic breast cancer, reflecting the strength of our underlying clinical data. Across European markets, we're seeing rapid uptake in HER2-positive metastatic breast cancer.

現在轉向恩赫圖。第一季度總收入增長 203%，達到 2.57 億美元。在美國，Enhertu 在二線 HER2陽性和激素受體陽性 HER2低化療後轉移性乳腺癌中的新患者份額現在約為 50%，反映了我們潛在臨床數據的強度。在整個歐洲市場，我們看到 HER2 陽性轉移性乳腺癌的快速吸收。

Finally, we achieved exciting regulatory milestones in the quarter, including first approvals in China for Calquence in mantle cell lymphoma and Enhertu in second-line HER2-positive metastatic breast cancer. Now please turn to Slide 15.

最後，我們在本季度實現了激動人心的監管里程碑，包括在中國首次批准用於套細胞淋巴瘤的 Calquence 和用於二線 HER2 陽性轉移性乳腺癌的 Enhertu。現在請轉到幻燈片 15。

In the past, we've made clear our ambition to transform patient outcomes in breast cancer, and you've seen our teams deliver towards achieving that goal. Now for the first time, we're laying out our ambition in lung cancer. And by the year 2030, we are aiming for at least half of all lung cancer patients to be eligible for an AstraZeneca medicine.

過去，我們明確表示要改變乳腺癌患者的治療結果，您已經看到我們的團隊為實現這一目標而付出的努力。現在，我們首次展示了我們在肺癌領域的雄心壯志。到 2030 年，我們的目標是讓至少一半的肺癌患者有資格使用阿斯利康藥物。

While this is a high bar, we've built a clear road map to deliver on this ambition, focusing first in late-stage non-small cell lung cancer, we have a broad portfolio of life cycle management and novel programs, and our success depends on our ability to deliver innovative medicines in both IO-sensitive and biomarker-driven tumor settings. Tagrisso is the established standard of care in adjuvant and frontline EGFR mutated non-small cell lung cancer and we're looking to solidify its position as the backbone TKI therapy in EGFR mutated space through additional combination trials. We are accelerating development of our next wave I-O assets, leveraging experience with Imfinzi across multiple tumor types and continuing to advance our ADC portfolio with Enhertu and Enhertu-expressing tumors and our TROP2 targeted ADC Dato-DX.

雖然這是一個很高的標準，但我們已經制定了一個明確的路線圖來實現這一目標，首先關注晚期非小細胞肺癌，我們擁有廣泛的生命週期管理和新項目組合，我們的成功取決於我們在 IO 敏感和生物標記驅動的腫瘤環境中提供創新藥物的能力。 Tagrisso 是輔助和一線 EGFR 突變非小細胞肺癌的既定護理標準，我們希望通過額外的聯合試驗鞏固其作為 EGFR 突變空間中骨幹 TKI 療法的地位。我們正在加速開發下一波 I-O 資產，利用 Imfinzi 在多種腫瘤類型方面的經驗，並繼續推進我們的 ADC 產品組合，包括 Enhertu 和表達 Enhertu 的腫瘤以及我們的 TROP2 靶向 ADC Dato-DX。

Furthermore, we have recently disclosed multiple registrational trials for both novel combination regimens and bispecifics. Underpinning this road map is also continued an important investment behind new technologies, including screening and testing tools as well as innovative platforms such as cell therapies. We're excited about the year ahead with important lung cancer data to support achievement of our 2030 ambition.

此外，我們最近披露了針對新型組合方案和雙特異性藥物的多項註冊試驗。支撐這一路線圖的還有對新技術的持續重要投資，包括篩选和測試工具以及細胞療法等創新平台。我們對未來一年的重要肺癌數據感到興奮，以支持實現我們 2030 年的雄心壯志。

And with that, please move to the next slide, and I'll transition to Susan to cover key R&D highlights.

然後，請轉到下一張幻燈片，我將轉給 Susan，介紹關鍵的研發亮點。

Thank you, Dave. Continuing on the theme of lung cancer. It's been an exciting quarter for early-stage disease, during which we've shared details of 2 key data sets that further validate the importance of moving lung cancer diagnosis and treatment to earlier stages of disease where patients have the highest potential for cure. First, at ACR, we shared the updated data from the AEGEAN trial. This tested the impact of adding Imfinzi to neoadjuvant chemotherapy and then continuing as adjuvant monotherapy. We'd already reported encouraging pathologic complete response data for this trial in June last year.

謝謝你，戴夫。繼續肺癌的主題。對於早期疾病來說，這是一個令人興奮的季度，在此期間，我們分享了 2 個關鍵數據集的詳細信息，這些數據集進一步驗證了將肺癌診斷和治療轉移到患者最有可能治癒的疾病早期階段的重要性。首先，在 ACR，我們分享了 AEGEAN 試驗的更新數據。這測試了將 Imfinzi 添加到新輔助化療中然後繼續作為輔助單一療法的影響。去年 6 月，我們已經報告了該試驗令人鼓舞的病理學完全緩解數據。

At AACR, we reported the planned interim analysis of event-free survival, which demonstrated that patients treated with the Imfinzi-based regimen had a 32% reduction in the risk of recurrence, progression events or death versus chemotherapy alone. We also shared updated pathologic complete response data showing a fourfold increase with the addition of Imfinzi compared to chemotherapy alone. We look forward to discussing these data with global regulatory authorities with the goal of providing this important new treatment option to patients.

在 AACR 上，我們報告了計劃中的無事件生存期中期分析，該分析表明，與單純化療相比，接受基於 Imfinzi 的方案治療的患者復發、進展事件或死亡的風險降低了 32%。我們還分享了最新的病理學完全緩解數據，顯示與單獨化療相比，添加 Imfinzi 可增加四倍。我們期待與全球監管機構討論這些數據，以期為患者提供這一重要的新治療選擇。

Second, last month, we shared positive high-level results from the ADAURA Phase III trial reporting that Tagrisso showed a strong overall survival benefit compared to placebo in the adjuvant treatment of patients with EGFR-mutated non-small cell lung cancer. This follows the encouraging data we presented at ESMO last year with continued benefit for Tagrisso in terms of disease-free survival and a median disease-free survival of nearly 5.5 years.

其次，上個月，我們分享了 ADAURA III 期試驗的積極高水平結果，該試驗報告稱，在 EGFR 突變的非小細胞肺癌患者的輔助治療中，與安慰劑相比，Tagrisso 顯示出很強的總體生存獲益。這是繼我們去年在 ESMO 上展示的令人鼓舞的數據之後，Tagrisso 在無病生存期和近 5.5 年的中位無病生存期方面持續受益。

The overall survival data, which we are delighted have been selected for an ASCO plenary at the first for a Phase III to demonstrate a survival benefit in this adjuvant setting. And they add to the extensive body of evidence generated for Tagrisso, which has now shown a statistically significant and clinically meaningful OS benefit in both the early adjuvant and late-stage metastatic settings reinforcing its standard of care position across lines.

我們很高興的總體生存數據已被 ASCO 全體會議首次選中用於 III 期，以證明在這種輔助環境中的生存益處。並且它們增加了為 Tagrisso 生成的大量證據，Tagrisso 現在已經顯示出在早期輔助和晚期轉移設置中具有統計學意義和臨床意義的 OS 益處，加強了其跨線護理地位的標準。

We've also had positive readouts from the DUO-O trial of Lynparza plus Imfinzi added to chemotherapy and bevacizumab in patients with newly diagnosed ovarian cancer without a BRCA mutation as well as a clinically meaningful data for Enhertu across multiple HER2 expressing tumor types from the DESTINY-PanTumor02 trial. Both these data sets will be showcased at ASCO this year. Please turn to Slide 17.

我們還從 DUO-O 試驗中獲得了陽性讀數，該試驗將 Lynparza 加 Imfinzi 添加到化療和貝伐珠單抗中，用於新診斷的沒有 BRCA 突變的卵巢癌患者，以及 Enhertu 在多種 HER2 表達腫瘤類型中的臨床意義數據DESTINY-PanTumor02 試驗。這兩個數據集都將在今年的 ASCO 上展示。請轉到幻燈片 17。

In addition to AEGEAN, AACR provided an opportunity for us to share data from across our diverse industry-leading oncology portfolio, including several highlights from our early-stage pipeline. We shared the first clinical data from the armoured GPC3 CAR T therapy, CCAR 31 in patients with advanced hepatocellular cancer as well as preclinical data for our armoured STEAP2 CAR-T AZD-0754 in prostate cancer models. Both these therapies have been designed using our dominant negative transforming growth factor beta receptor armouring, which aims to resist the immunosuppressive tumor microenvironment and enhance the potential effectiveness of CAR-T in solid tumors.

除了 AEGEAN 之外，AACR 還為我們提供了一個機會，讓我們可以共享來自我們不同行業領先的腫瘤產品組合的數據，包括我們早期管道中的幾個亮點。我們分享了晚期肝細胞癌患者的裝甲 GPC3 CAR T 療法 CCAR 31 的第一個臨床數據，以及我們的裝甲 STEAP2 CAR-T AZD-0754 在前列腺癌模型中的臨床前數據。這兩種療法都是使用我們占主導地位的負性轉化生長因子β受體裝甲設計的，旨在抵抗免疫抑制性腫瘤微環境並增強 CAR-T 在實體瘤中的潛在有效性。

We're encouraged by 3 out of 6 deep and durable responses at the second dose level and the persistence of CAR-T copies out to at least 149 days, which is substantially more than has been observed with any other GPC3 CAR T products.

我們感到鼓舞的是，在第二劑量水平下，6 種深度和持久的反應中有 3 種以及 CAR-T 拷貝的持續存在至少 149 天，這大大超過任何其他 GPC3 CAR T 產品所觀察到的時間。

We also presented preclinical data from our in-house ADC platform. Our ADCs have been designed to maximize therapeutic index with a proprietary link of payload. The platform has a novel potent to price on rose 1 inhibitor, which provide by standard tumor kill activity and a linker designed to provide a high degree of stability in the peripheral circulation with minimal free payload exposure.

我們還展示了來自我們內部 ADC 平台的臨床前數據。我們的 ADC 旨在通過專有的有效載荷鏈接最大限度地提高治療指數。該平台對 rose 1 抑製劑具有新的定價潛力，它通過標準的腫瘤殺傷活性和一個連接器提供，旨在在外周循環中提供高度穩定性，同時最大限度地減少游離有效載荷暴露。

AZD9592, a bispecific ADC targeting EGFR unmet and AZD8205 targeting B7-H4 are already in Phase I. And AZD5335 targeting folate receptor alpha will enter the clinic later this year.

AZD9592，一種靶向 EGFR 未滿足的雙特異性 ADC 和靶向 B7-H4 的 AZD8205 已經進入 I 期。靶向葉酸受體 α 的 AZD5335 將於今年晚些時候進入臨床。

Finally, we provided our first disclosure for the novel lead epigenetics molecule. AZPRMT5 inhibitor, which is a potent MTAP selective PRMT5 inhibitor with antitumor activity in MTAP-deleted tumors. Loss of the MTAP gene occurs across approximately 15% of all tumors, and this provides an opportunity to selectively target these tumors and spare healthy tissue. This program will enter Phase 1 shortly.

最後，我們首次披露了新型先導表觀遺傳學分子。 AZPRMT5 抑製劑，它是一種有效的 MTAP 選擇性 PRMT5 抑製劑，在 MTAP 缺失的腫瘤中具有抗腫瘤活性。 MTAP 基因的缺失發生在大約 15% 的所有腫瘤中，這提供了選擇性靶向這些腫瘤並保留健康組織的機會。該計劃將很快進入第一階段。

And with this, please advance to the next slide, and I'll hand over to Ruud to cover biopharmaceuticals performance.

有了這個，請轉到下一張幻燈片，我將交給 Ruud 來介紹生物製藥的性能。

Thank you, Susan. Please turn to Slide 19. Total revenue from biopharmaceuticals was $4.5 billion in the quarter with CVRM growing 22% and R&I growing 8%. Revenues from our COVID-19 medicines declined to $155 million due to the completion of our vaccine contracts last year and lower average shelf sales in the United States and Europe. Farxiga continued to be the main driver in global CVRM, growing 39% to $1.3 billion, driven by multiple geographies, including the U.S., Europe, Japan and the emerging markets. Although it's worth noting that Farxiga enjoyed some gross to net benefits in quarter 1 that may not recur in future quarters.

謝謝你，蘇珊。請轉到幻燈片 19。本季度生物製藥的總收入為 45 億美元，其中 CVRM 增長 22%，R&I 增長 8%。由於我們去年的疫苗合同完成以及美國和歐洲的平均貨架銷售額下降，我們 COVID-19 藥物的收入下降至 1.55 億美元。在美國、歐洲、日本和新興市場等多個地區的推動下，Farxiga 繼續成為全球 CVRM 的主要驅動力，增長 39% 至 13 億美元。儘管值得注意的是，Farxiga 在第一季度享有一些毛淨收益，但在未來幾個季度可能不會再出現。

We also saw over 60% growth for roxadustat in China and for Lokelma globally. Lokelma is now available in 27 markets, having achieved potassium binder market share leadership in 8 of these markets.

我們還看到 roxadustat 在中國和 Lokelma 在全球的增長超過 60%。 Lokelma 現在在 27 個市場有售，並在其中 8 個市場取得了鉀粘合劑市場份額的領先地位。

R&I's growth to $1.6 billion was helped by a recovery of demand for inhaled products in China as lockdown restrictions eased and also strong growth in Europe and other emerging markets. Please turn to Slide 20.

隨著封鎖限制的放鬆，中國對吸入產品的需求復蘇，以及歐洲和其他新興市場的強勁增長，R&I 增長至 16 億美元。請轉到幻燈片 20。

Over the last 2 years, the downward trends in Symbicort, Pulmicort and other older brands has been more than offset by growth from Fasenra, Tezspire, Saphnelo and Breztri. These combined brands grew at 46% in quarter 1, and they now make up over 1/3 of RNI revenue.

在過去 2 年中，Fasenra、Tezspire、Saphnelo 和 Breztri 的增長足以抵消 Symbicort、Pulmicort 和其他老品牌的下降趨勢。這些合併後的品牌在第一季度增長了 46%，現在佔 RNI 收入的 1/3 以上。

Biologics are a fast-growing class of medicines and only 1/5 of patients who are eligible for biologic medicine are currently receiving 1. Fasenra continues to sustain leadership in total market share in severe eosinophilic asthma. And Tezspire's launch momentum continues at a rapid pace. In quarter 1, we saw continued growth in the U.S. and rapid uptake elsewhere in Japan -- and rapid uptake elsewhere. In Japan, Tezspire has already captured new-to-brand absolute leadership just a few months after launch. Tezspire is now available in 6 markets, and the auto-injector was approved in the U.S. and the EU at the start of the year.

生物製劑是一類快速增長的藥物，目前只有 1/5 有資格獲得生物藥物的患者正在接受 1。Fasenra 繼續在嚴重嗜酸性粒細胞哮喘的總市場份額中保持領先地位。 Tezspire 的發布勢頭繼續保持快速增長。在第一季度，我們看到美國的持續增長和日本其他地方的快速吸收——以及其他地方的快速吸收。在日本，Tezspire 在推出僅幾個月後就已經佔據了新品牌的絕對領導地位。 Tezspire 現已在 6 個市場上市，自動注射器於今年年初在美國和歐盟獲得批准。

Our inhaled portfolio also contains innovative medicines that have a long life cycle ahead. Next year, Airsupra will add a fifth medicine to our newly launched brands. And in quarter 1, Breztri grew 73%. Breztri is benefiting from increased awareness of triple therapies, which was boosted by the 2023 report for the global initiative for chronic obstructive lung disease. The report applicated a shortened path to triple fixed dose therapies in order to reduce mortality.

我們的吸入產品組合還包含具有較長生命週期的創新藥物。明年，Airsupra 將在我們新推出的品牌中添加第五種藥物。在第一季度，Breztri 增長了 73%。 Breztri 受益於人們對三聯療法認識的提高，這得益於 2023 年慢性阻塞性肺病全球倡議的報告。該報告採用了一種縮短的三倍固定劑量療法路徑，以降低死亡率。

In recent quarters, Breztri has accelerated new patient share gains in the U.S. and Europe and retained its leadership position in China with a 70% share of new-to-brand prescriptions. This quarter, we also announced a new production site in Qingdao, which will support Breztri's continuous growth in China, which is home to 100 million patients with COPD.

最近幾個季度，Breztri 在美國和歐洲加快了新患者份額的增長，並以 70% 的新品牌處方份額保持其在中國的領先地位。本季度，我們還宣布了在青島的新生產基地，這將支持 Breztri 在中國的持續增長，中國擁有 1 億慢性阻塞性肺病患者。

With that, I will now hand over to Mene, who will discuss the development programs that will drive future innovation of our biopharmaceuticals portfolio.

有了這個，我現在將交給 Mene，他將討論將推動我們生物製藥產品組合未來創新的開發計劃。

Thank you, Ruud, and please turn to Slide 21. This slide outlines our assets across asthma and COPD. And as Ruud highlighted, we have a strong legacy in respiratory medicine with our broad portfolio, we're committed to continued respiratory leadership. Here, we highlight the breadth of our commercial portfolio and illustrate our focus on emerging science involving immune mechanisms, lung damage and cell repair processes. Our on-market inhaled medicines are already considered frontline standard therapies. And we're also developing a number of novel add-on oral inhaled and biologic therapies for patients whose diseases are not adequately controlled by existing medicines.

謝謝 Ruud，請轉到幻燈片 21。這張幻燈片概述了我們在哮喘和 COPD 方面的資產。正如 Ruud 強調的那樣，我們憑藉廣泛的產品組合在呼吸醫學領域擁有深厚的底蘊，我們致力於繼續保持呼吸領域的領導地位。在這裡，我們強調了我們商業組合的廣度，並說明了我們對涉及免疫機制、肺損傷和細胞修復過程的新興科學的關注。我們上市的吸入藥物已被視為一線標準療法。我們還在為現有藥物無法充分控制疾病的患者開發多種新型附加口服吸入療法和生物療法。

Our IL33 targeted antibody to tozorakimab offers a differentiated mechanism of action. The reduced form of IL33 regulates the ST2 pathway responsible for inflammatory drive, whilst the oxidized form of IL33 regulates the rage pathway responsible for epithelial dysfunction and mucus production. Tozorakimab inhibits both signaling pathways with the potential to reverse key pathogenic features of COPD. Tezspire, our anti-TSLP remains the first and only biologic in asthma approved without biomark or phenotype. TSLP is an epithelial cytokine that sits at the top of multiple inflammatory cascades, and it's critical in the initiation and persistence of multiple drivers of airway inflammation. We also have several other early-stage assets in our pipeline, including inhaled TSLP and inhaled JAK, which should enter Phase II in the second half of this year based on solid proof of mechanism data.

我們針對 tozorakimab 的 IL33 靶向抗體提供了差異化的作用機制。 IL33 的還原形式調節負責炎症驅動的 ST2 通路，而 IL33 的氧化形式調節負責上皮功能障礙和粘液產生的憤怒通路。 Tozorakimab 抑制兩種信號通路，有可能逆轉 COPD 的關鍵致病特徵。 Tezspire，我們的抗 TSLP 仍然是第一個也是唯一一個在沒有生物標誌物或表型的情況下獲得批准的哮喘生物製劑。 TSLP 是一種上皮細胞因子，位於多個炎症級聯反應的頂端，它對於多種氣道炎症驅動因素的啟動和持續至關重要。我們還有其他幾個早期資產在我們的管線中，包括吸入 TSLP 和吸入 JAK，根據可靠的機制數據證明，它們應該在今年下半年進入 II 期。

We are confident this rich pipeline will provide the right building blocks to continue to drive leadership in respiratory diseases over the long term. Please turn to the next slide.

我們相信，這一豐富的管道將提供正確的基石，繼續推動長期在呼吸系統疾病領域的領導地位。請翻到下一張幻燈片。

At AAN, we presented 66 weeks data for eplontersen in [ATTR] polyneuropathy building on the 35-week data presented last year at ISA. We saw a statistically significant and clinically meaningful change from baseline versus an external placebo on the co-primary endpoints of reduction of transthyretin and on the modified neuropathy impairment score plus 7 as well as the Norfolk Quality of Life questionnaire. It was really encouraging to see the continued improvement on the quality of life questionnaire, which is designed to capture and quantify the impact of neuropathy on the lives of patients. ATTRv-PN patients have identified sensory deficits and autoimmune GI symptoms as the most difficult symptoms to manage and thus, continued and sustained improvement in the quality of life questionnaire is an important indication of clinical benefit for these patients.

在 AAN 上，我們基於去年在 ISA 上展示的 35 週數據，展示了 eplontersen 在 [ATTR] 多發性神經病中的 66 週數據。在轉甲狀腺素蛋白減少和改良神經病變損傷評分加 7 以及諾福克生活質量問卷等共同主要終點方面，我們發現與基線相比，外部安慰劑有統計學意義和臨床意義的變化。看到生活質量問卷的持續改進真的很令人鼓舞，該問卷旨在捕捉和量化神經病變對患者生活的影響。 ATTRv-PN 患者已將感覺缺陷和自身免疫性 GI 症狀確定為最難管理的症狀，因此，持續不斷地改善生活質量問卷是這些患者臨床獲益的重要指標。

We look forward to sharing this data with the regulators globally as we seek approval for eplontersen. At ECCMID, we also provided new data on AZD3152, our COVID-19 long-acting antibody. In vitro studies demonstrated that AZD3152 neutralizes all COVID-19 variants, including Arcturus, the latest variant of concern. And we hope to make AZD3152 available as a new prophylactic treatment in the second half of this year. Please turn to Slide 23.

在我們尋求 eplontersen 的批准時，我們期待與全球監管機構共享這些數據。在 ECCMID，我們還提供了關於 AZD3152（我們的 COVID-19 長效抗體）的新數據。體外研究表明，AZD3152 可中和所有 COVID-19 變體，包括最新的令人擔憂的變體 Arcturus。我們希望在今年下半年將 AZD3152 作為一種新的預防性治療藥物上市。請轉到幻燈片 23。

As Aradhana discussed earlier, artificial intelligence is embedded across our organization. And within R&D, we're using AI across all our therapy areas to discover new medicines more efficiently. Understanding the biology of disease is critical to identifying the right drug targets and pathways is one of the most important decisions we make in drug discovery. We're applying AI and machine learning to build biomedical knowledge graphs across all our disease areas. And these visual representations depict relationships between vast data sets derived both within and external to AstraZeneca.

正如 Aradhana 之前討論的那樣，人工智能已融入我們的整個組織。在研發方面，我們在所有治療領域使用 AI 來更有效地發現新藥。了解疾病的生物學對於確定正確的藥物靶點和途徑至關重要，這是我們在藥物發現過程中做出的最重要的決定之一。我們正在應用人工智能和機器學習來構建涵蓋我們所有疾病領域的生物醫學知識圖譜。這些視覺表示描繪了阿斯利康內部和外部的大量數據集之間的關係。

And our scientists use these knowledge grafts to glean novel insights into disease biology as well as new pathways and targets to prosecute. AI-enabled processes are also transforming the discovery of small and large molecule leads. Within small molecule drug discovery, we use proprietary AI-enabled platforms to generate small molecules twice as fast as our traditional discovery processes. These algorithms use both generative models and novel scoring functions.

我們的科學家利用這些知識嫁接來收集對疾病生物學的新見解以及新的途徑和目標進行起訴。支持 AI 的流程也正在改變小分子和大分子先導物的發現。在小分子藥物發現中，我們使用專有的 AI 支持平台生成小分子，其速度是我們傳統發現過程的兩倍。這些算法同時使用生成模型和新穎的評分函數。

In antibody discovery, we use AI-enabled deep screening programs to identify potential lead antibodies in as little as 3 days compared to traditional methods, which takes several months. The scale and pace with which these new AI and machine learning innovations can accelerate drug discovery is really exciting, and we look forward to providing additional examples of AI-driven innovation over the balance of the year.

在抗體發現中，我們使用支持 AI 的深度篩選程序在短短 3 天內識別出潛在的先導抗體，而傳統方法需要幾個月的時間。這些新的 AI 和機器學習創新可以加速藥物發現的規模和速度確實令人興奮，我們期待在今年餘下時間提供更多 AI 驅動創新的例子。

Please move to the next slide, and I will now hand over to Marc to cover Rare Diseases.

請轉到下一張幻燈片，我現在將交給 Marc 來介紹罕見病。

Thank you, Mene. Please move to Slide 25.

謝謝你，梅內。請移至幻燈片 25。

In the first quarter, Rare Disease total revenues grew 14%, contributing $1.9 billion. The strong performance in the quarter was primarily driven by patient demand as well as some benefit from certain tender market orders. Ultomiris grew 61% in the quarter, reflecting successful and accelerated conversion from Soliris across shared indications. myasthenia gravis, we saw an increased number of complement neve patients treated with Ultomiris, advancing our ambition to expand Ultomiris issues into a broader option population, which we estimate to be 2 to 3x larger than the addressable Soliris patient population. Consequently, Soliris declined 13% in the quarter as conversion accelerated. However, this decline was partially offset by growth in NMO and tender market order timing in certain emerging markets.

第一季度，罕見病總收入增長了 14%，貢獻了 19 億美元。本季度的強勁表現主要是由患者需求以及某些招標市場訂單帶來的一些好處所推動的。 Ultomiris 在本季度增長了 61%，反映出 Soliris 在共享適應症上的成功和加速轉換。重症肌無力，我們看到接受 Ultomiris 治療的補體神經元患者數量增加，這推動了我們將 Ultomiris 問題擴展到更廣泛的選擇人群的雄心，我們估計該人群比可尋址的 Soliris 患者人群大 2 至 3 倍。因此，隨著轉換加速，Soliris 在本季度下降了 13%。然而，這一下降部分被某些新興市場 NMO 的增長和招標市場訂單時間所抵消。

Though we are excited by this strong performance in the quarter, I want to mention a couple of key dynamics. First, as we continue to execute a conversion strategy from Soliris to Ultomiris, Ultomiris annual treatment cost is approximately 1/3 lower than Soliris. Furthermore, additional indication from Ultomiris require negotiation in some legislations as the eligible patient population expands. Therefore, as we move from ultrarare such as PNH to rare population, such as myasthenia gravis, we anticipate increased pricing pressure. We fully expect the patient volume growth to offset the impact of this negotiation, although they present pricing headwinds in the near term.

儘管我們對本季度的強勁表現感到興奮，但我想提幾個關鍵動態。首先，隨著我們繼續執行從 Soliris 到 Ultomiris 的轉換策略，Ultomiris 的年度治療成本比 Soliris 低約 1/3。此外，隨著符合條件的患者群體的擴大，Ultomiris 的額外適應症需要在一些立法中進行談判。因此，隨著我們從 PNH 等超罕見疾病轉向重症肌無力等罕見人群，我們預計定價壓力會增加。我們完全預計患者數量的增長將抵消這次談判的影響，儘管它們在短期內會帶來定價阻力。

We remain confident in our C5 franchise, conversion and expansion strategies. And for the full year, we expect Ultomiris revenue to be broadly in line with that of Soliris. Beyond the complement, Strensiq grew 28% and Koselugo grew over 2x in the first quarter, driven by strength of patient demand and geographic expansion. Please move to next slide.

我們對我們的 C5 特許經營、轉換和擴張戰略充滿信心。對於全年，我們預計 Ultomiris 的收入將與 Soliris 的收入大致持平。除了補充之外，在患者需求強勁和地域擴張的推動下， Strensiq 在第一季度增長了 28%， Koselugo 增長了 2 倍以上。請移至下一張幻燈片。

At the American Academy of Neurology Congress earlier this week, we presented data across myasthenia gravis, NMO and dermatomyositis. Notably, we presented real-world data, highlighting the clinical benefit of C5 inhibition, evaluating the change in concomitant therapies for patient receiving Soliris. In practice, HCPs initially treat patients with high-dose oral corticosteroids to manage symptoms. And then when symptoms are under control, they evaluate the use of additional therapies to sustain symptom control and ultimately look to minimize steroid usage. At 1 year treatment with Soliris, 76% of patients reduce the high-dose steroid use further demonstrating the clinical benefit of C5 inhibition on patient outcomes. We hope to show a similar reduction in Ultomiris registry where analysis is ongoing.

在本週早些時候的美國神經病學學會大會上，我們展示了重症肌無力、NMO 和皮肌炎的數據。值得注意的是，我們提供了真實世界的數據，強調了 C5 抑制的臨床益處，評估了接受依庫珠單抗治療的患者伴隨治療的變化。在實踐中，HCP 最初使用大劑量口服皮質類固醇治療患者以控制症狀。然後，當症狀得到控制時，他們會評估使用其他療法來維持症狀控制，並最終尋求盡量減少類固醇的使用。在 Soliris 治療 1 年時，76% 的患者減少了高劑量類固醇的使用，進一步證明了 C5 抑制對患者預後的臨床益處。我們希望在正在進行分析的 Ultomiris 註冊表中顯示類似的減少。

We have highlighted new Phase I data in our third-generation C5 inhibitor, gefurulimab, a novel bi-specific heavy chain antibody. It's low molecule weight enable subcutaneous self-administration, binding to albumin to extend half-life, which allows for convenient weekly dosing. The results demonstrated gefurulimab, favorable safety and tolerability profile as well as its ability to achieve near complete terminal complement inhibition. This data further supports our ongoing direct to Phase III prevailed trial in adult myasthenia gravis.

我們重點介紹了我們的第三代 C5 抑製劑 gefurulimab（一種新型雙特異性重鏈抗體）的新 I 期數據。它的低分子量使其能夠皮下自我給藥，與白蛋白結合以延長半衰期，從而方便每週給藥。結果表明，gefurulimab 具有良好的安全性和耐受性，以及實現接近完全末端補體抑制的能力。該數據進一步支持了我們正在進行的成人重症肌無力直接至 III 期普遍試驗。

Separately, following discussions with regulatory authorities, I'm disappointed to announce the termination of our Alexion 1840 Wilson disease program despite positive results from the Phase III FOCUS trial announced in 2021. Data from the program will be presented at an upcoming medical congress. Please turn to next slide.

另外，在與監管機構討論後，我很失望地宣布終止我們的 Alexion 1840 Wilson 病項目，儘管 2021 年宣布的 III 期 FOCUS 試驗取得了積極成果。該項目的數據將在即將舉行的醫學大會上公佈。請翻到下一張幻燈片。

In addition to our strength in C5, I also wanted to highlight our complement Factor D inhibitor. Factor D is the regulator of the alternative pathway upstream of C5. The selective inhibition of the alternative pathway allows the other pathways to remain intact to fight infection, and this may provide a safety advantage. We believe that Factor D is the most tractable target given its stable circulating concentration in the plasma. With 3 differentiated assets, our Factor D portfolio has a potential to unlock value in several indications, including PNH, myasthenia gravis, geographic atrophy and renal indications.

除了我們在 C5 方面的優勢外，我還想強調我們的補體 D 因子抑製劑。因子 D 是 C5 上游替代途徑的調節劑。替代途徑的選擇性抑制允許其他途徑保持完整以抵抗感染，這可能提供安全優勢。我們認為，鑑於因子 D 在血漿中的穩定循環濃度，它是最易處理的靶標。憑藉 3 種差異化資產，我們的 Factor D 產品組合有可能在多種適應症中釋放價值，包括 PNH 、重症肌無力、地圖樣萎縮和腎臟適應症。

Our most clinically advanced is danicopan, which most recently was submitted for regulatory approval in PNH patients with clinically significant extravascular hemolysis. We have also seen positive Phase II from [haemoglobinuria] as a monotherapy in PNH and Alexion 2080, the third of Factor D has recently dosed in Phase I. We look forward to providing further updates on our Factor D portfolio and our broader pipeline in future quarters.

我們臨床上最先進的藥物是達尼可泮，它最近已提交監管機構批准用於治療具有臨床顯著血管外溶血的 PNH 患者。我們還看到 [血紅蛋白尿] 的 II 期陽性作為 PNH 和 Alexion 2080 的單一療法，D 因子的第三種最近在 I 期給藥。我們期待在未來提供關於我們的因子 D 產品組合和更廣泛管道的進一步更新宿舍。

Please turn to Slide 29, and I will hand the call back to Pascal for closing remarks.

請轉到幻燈片 29，我會將電話轉回給 Pascal 以作結束語。

Thank you, Marc. So if we move to the next slide, please. So for the reminder of 2023, we have a number of important trial readouts that have the potential to redefine care for patients. This include the first Phase III trial of Dato-DXd in lung cancer. And I'm pleased to tell you that we now expect the results from a second trial Dato-DXd. TROPION-Breast01 in the second half of this year.

謝謝你，馬克。那麼，請轉到下一張幻燈片。因此，對於 2023 年的提醒，我們有許多重要的試驗讀數，它們有可能重新定義對患者的護理。這包括 Dato-DXd 在肺癌中的第一個 III 期試驗。我很高興地告訴你，我們現在期待第二次試驗 Dato-DXd 的結果。今年下半年的 TROPION-Breast01。

Finally, we are making excellent progress towards our medium- and long-term strategic ambitions, and I'm thrilled to announce we are the top-ranked pharmaceutical company on the financial time 2023, Europe Climate Leaders list. Looking ahead, this is shaping up to be another exciting year for our company, and I look forward to updating you on our progress.

最後，我們在實現中長期戰略目標方面取得了出色的進展，我很高興地宣布，我們在《金融時報》2023 年歐洲氣候領袖榜單中名列前茅。展望未來，今年將是我們公司又一個激動人心的一年，我期待著向您介紹我們的最新進展。

With that, I'll hand the call back to Andy.

有了這個，我會把電話轉回給安迪。

Thank you, Pascal. We'll now move to the Q&A with all of our executive team members participating shown here. (Operator Instructions) With that, let's move to the first question.

謝謝你，帕斯卡。我們現在將進入問答環節，我們所有的執行團隊成員都參加了這裡的展示。 （操作員說明）有了這個，讓我們轉到第一個問題。

The first question is from Sachin of BofA.

第一個問題來自美國銀行的薩欽。

Two questions, please. First topic is Dato-DXd 2-part, TLO2 and 04 at your ASCO. So I wonder if Susan, if you could just give us some color on what we should be looking for? Are we expecting PFS data? And is it fair to be comparing that to KEYNOTE-189 as we think about confidence into 07 and 08? And then just on the breast data, you mentioned Pascal TB01 and you've also got TB02 in TNBC next year. So wondering if Dave could just frame for us how we think about the commercial opportunity of these 2 indications that haven't really been discussed much by investors? It feels to us like there could be (inaudible) billion opportunity combined. Any thoughts there? And then a quick follow-on for Dave on Calquence. Just wondering if you could give a bit more detail on the Beijing competition you're seeing?

請教兩個問題。第一個主題是您 ASCO 的 Dato-DXd 2 部分、TLO2 和 04。所以我想知道 Susan 是否可以給我們一些關於我們應該尋找什麼的顏色？我們期待 PFS 數據嗎？當我們考慮對 07 和 08 的信心時，將其與 KEYNOTE-189 進行比較是否公平？然後就乳房數據而言，你提到了 Pascal TB01，明年 TNBC 也有 TB02。所以想知道 Dave 是否可以為我們構建我們如何看待投資者尚未真正討論過的這兩個適應症的商業機會？在我們看來，可能會有（聽不清）十億的機會。有什麼想法嗎？然後是 Dave 在 Calquence 上的快速跟進。只是想知道您能否更詳細地介紹一下您正在觀看的北京比賽？

Thanks very much, Sachin. So Susan, do you want to take the first one? Or should we see -- and then, Dave, you'll take the other one?

非常感謝，薩欽。蘇珊，你想選第一個嗎？或者我們應該看看——然後，戴夫，你會選擇另一個嗎？

Yes, sure. So obviously, with the TLO2, we're going to have updated data with the combination of Dato-DXd with immuno-oncology agents. And again, with TLR4. And we have data in combination with chemotherapy plus other agents. So I think you can look at durable response rate. It's always difficult to look at endpoints like recussion-free survival and single-arm studies because there are differences in patient populations that are accrued versus other things that are out there. But that's what I suggest you look for.

是的，當然。很明顯，對於 TLO2，我們將通過 Dato-DXd 與免疫腫瘤藥物的結合來更新數據。再一次，使用 TLR4。我們有結合化療和其他藥物的數據。所以我認為你可以看看持久響應率。總是很難查看無復發生存期和單臂研究等終點，因為累積的患者群體與其他存在的患者群體存在差異。但這就是我建議你尋找的。

Great. So on Sachin, your first question around the opportunity with Dato in breast cancer. Maybe the first thing that I would just point out here, and we talked about this in the context of DESTINY-Breast04 and DESTINY-Breast06, a large number of breast cancer patients in the metastatic setting, hormone receptor positive and triple-negative were treated today with systemic chemotherapy. And we think we've got one of the leading antibody drug conjugate portfolios between Enhertu and Dato to be able to hopefully replace much of that chemotherapy use today with antibody drug conjugates. And so there's certainly a multi-blockbuster opportunity in breast cancer to replace that systemic chemotherapy.

偉大的。所以關於 Sachin，你的第一個問題是關於 Dato 治療乳腺癌的機會。也許我要在這裡指出的第一件事，我們在 DESTINY-Breast04 和 DESTINY-Breast06 的背景下討論過，大量處於轉移性、激素受體陽性和三陰性的乳腺癌患者接受了治療今天進行全身化療。我們認為我們在 Enhertu 和 Dato 之間擁有領先的抗體藥物偶聯物組合之一，有望用抗體藥物偶聯物取代當今大部分化療藥物的使用。因此，在乳腺癌中肯定有一個重磅炸彈的機會來取代全身化療。

Now exactly how the puzzle piece is in the overlap between 04, 06, TROPION-Breast01. I think we need to see some of the data and how that plays out. But I'd encourage you to think about and that's the reason we talk about kind of the breast cancer as a portfolio. I talked about lung cancer as a portfolio today because I think that we've got an opportunity across those assets to be able to really create very good commercial opportunity by replacing systemic chemo.

現在拼圖在 04、06、TROPION-Breast01 之間的重疊部分是怎樣的。我認為我們需要查看一些數據以及結果如何。但我鼓勵你考慮一下，這就是我們將乳腺癌作為投資組合來討論的原因。我今天談到肺癌作為一個投資組合，因為我認為我們有機會跨越這些資產，能夠通過取代全身化療來真正創造非常好的商業機會。

Maybe the last just kind of point here of note on TB01. So that study is in a post endocrine therapy and post first systemic therapy. That's an earlier line than what we've seen out of TROPiCS-02. So I think that, that gives you a sense competitively too, that it's well positioned competitively depending on the data.

也許這裡是關於 TB01 的最後一點注意事項。因此，該研究是在內分泌治療後和首次全身治療後進行的。這比我們從 TROPiCS-02 中看到的要早。所以我認為，這也給了你一種競爭感，即根據數據，它在競爭中處於有利地位。

On Calquence and what we've been seeing there, we continue to win the overwhelming majority of new starts in the frontline CLL setting. This is really our key area of promotional focus. In terms of market share, we are seeing impact from zanu as a new entrant. We've seen the majority of their impact come in the relapsed/refractory setting. We have seen some impact come in the frontline setting. Some of their impact in the frontline setting has come at the expense of Calquence, though the majority of it has come at the expense of ibrutinib, the first-generation BTKI.

在 Calquence 和我們在那裡看到的情況下，我們繼續在前線 CLL 設置中贏得絕大多數新開始。這確實是我們促銷重點的重點領域。在市場份額方面，我們看到了 zanu 作為新進入者的影響。我們已經看到它們的大部分影響來自複發/難治性環境。我們已經看到一線環境產生了一些影響。他們在一線環境中的一些影響是以犧牲 Calquence 為代價的，儘管其中大部分是以犧牲第一代 BTKI ibrutinib 為代價的。

I would also say that within this context, we certainly expect the BTK market to be competitive going forward. I'm quite confident that our team is very well prepared. We have important data coming out at ASCO on a matched analysis indirect comparison between Ascend and Alpine that we're hearing early positive response from investigators on and we'll continue to work hard to keep Calquence as the clear standard of care within the frontline setting.

我還要說，在這種情況下，我們當然希望 BTK 市場在未來具有競爭力。我非常有信心我們的團隊已經做好了充分的準備。我們在 ASCO 上發布了關於 Ascend 和 Alpine 之間匹配分析間接比較的重要數據，我們從調查人員那裡聽到了早期的積極回應，我們將繼續努力保持 Calquence 作為前線環境中明確的護理標準.

Thanks, Dave. James Gordon at JPM. Go ahead, James.

謝謝，戴夫。摩根大通的詹姆斯戈登。來吧，詹姆斯。

James Gordon from JPMorgan. 2, please. What about the C5 franchise and also competition. So Novartis presented their detailed, (inaudible) Factor B data. And it did suggest potentially competitive efficacy versus Soliris and Ultomiris and it's oral. But -- do you think it does look competitive? How should we read that data? Can we compare it to what you've shown for Soliris and Ultomiris in PNH? And you mentioned you've got a few things of your own. So you've got to Factor Ds, but is the focus more the Factor Ds now? Or is the excitement more actually on 17, 20? And when do you think you could have either 17, 20 or a monotherapy, a Factor D in the market to compete with Novartis?

摩根大通的詹姆斯戈登。 2，請。 C5 特許經營權和競爭情況如何。因此，諾華公司展示了他們詳細的（聽不清）因子 B 數據。它確實表明與 Soliris 和 Ultomiris 相比具有潛在的競爭功效，而且它是口服的。但是——你認為它看起來很有競爭力嗎？我們應該如何讀取這些數據？我們可以將它與您在 PNH 中展示的 Soliris 和 Ultomiris 進行比較嗎？你提到你有一些自己的東西。所以你必須要考慮因素 D，但現在更關注因素 D 了嗎？還是 17、20 日更讓人興奮？你認為你什麼時候可以在市場上使用 17、20 或單一療法，一種 D 因子來與諾華競爭？

And the second question was just Imfinzi and really strong performance in Q1. Can you break down the performance a bit? Is much of that -- the acceleration coming from (inaudible)? And is the performance very front-end weighted because Imjudo you charge more upfront and then it sort of tapers off over the patient's treatment? Or is this like a clean Q1 number we can extrapolate from for the rest of the year?

第二個問題只是 Imfinzi 和 Q1 的強勁表現。你能分解一下表演嗎？其中大部分 - 加速度來自（聽不清）？性能是否非常重視前端，因為 Imjudo 預先收取更多費用，然後隨著患者的治療逐漸減少？或者這就像我們可以推斷今年剩餘時間的干淨的 Q1 數字？

So James, actually, thank you. The first question was actually 2 questions. So it's 3 questions in total. Marc, do you want to take the first 2 and C5 franchise and (inaudible) and also then the Factor D portfolio versus 1720?

所以詹姆斯，實際上，謝謝你。第一個問題實際上是2個問題。所以一共是3道題。馬克，你想拿前 2 和 C5 特許經營權和（聽不清），然後是因素 D 投資組合與 1720？

Yes. So first of all, the first -- the question on iptacopan recent data versus C5. So first of all, I would like to caution everybody on doing indirect comparison of very different clinical trials especially when the population that are included in the trials are very different just to provide an illustration of that, the C5 inhibitors of Alexion (inaudible) usually include bone marrow failure patient, who do represent about 30% to 40% of the actual PNH population.

是的。首先，關於 iptacopan 最近數據與 C5 的問題。所以首先，我想提醒大家不要對非常不同的臨床試驗進行間接比較，尤其是當試驗中包含的人群非常不同時，只是為了說明這一點，Alexion 的 C5 抑製劑（聽不清）通常包括骨髓衰竭患者，他們確實佔實際 PNH 人口的 30% 到 40%。

The second difference, the second visible difference is that the trials of iptacopan are enriched with EVH, extravascular hemolysis and anemia patients suffering from anemia. And therefore, when you measure improvement of hemoglobin, it's probably easier to demonstrate the benefit.

第二個區別，第二個可見的區別是iptacopan的試驗中富集了患有EVH、血管外溶血和貧血的貧血患者。因此，當您測量血紅蛋白的改善時，可能更容易證明其益處。

But just to go back to the comparison, we -- as you have said, James, we also believe in the potential for proximal inhibitors Factor B or Factor D to play a role in the treatment of PNH. Whether this will be in cotherapy as we have already demonstrated with danicopan, or first Factor D or whether it will be in monotherapy as we are trying to demonstrate in Vemircopan. We -- this needs -- remains to be seen. The key objective for PNH are obviously the control of intravascular hemolysis and to prevent thrombosis, otherwise, you are increasing significantly the mortality risk. So we need to be seeing these results over time. Again, core therapy versus monotherapy.

但回到比較，我們——正如你所說，詹姆斯，我們也相信近端抑製劑因子 B 或因子 D 有可能在 PNH 的治療中發揮作用。這是否會像我們已經用 danicopan 或第一個因子 D 證明的那樣進行聯合治療，或者是否會像我們試圖在 Vemircopan 中證明的那樣進行單藥治療。我們——這需要——還有待觀察。 PNH 的主要目標顯然是控制血管內溶血和防止血栓形成，否則，您將顯著增加死亡風險。所以我們需要隨著時間的推移看到這些結果。同樣，核心療法與單一療法。

To turn to your second question -- or third question, all in all, is 1720. For us, 1720 is an improved generation over the first 2 C5, it's a subcut formulation provided on a weekly regimen, we are still continuing the development. We see -- we have a trial in myasthenia gravis that is progressing very well. So we are not abandoning the third generation of C5. We're also exploring the Factor D. And as I described in my script, we have 3 of these Factor D and each of them will be positioned slightly differently across the development momentum.

轉向你的第二個問題——或第三個問題，總而言之，是 1720。對我們來說，1720 是第一代 2 C5 的改進一代，它是按每周方案提供的細分配方，我們仍在繼續開發。我們看到 - 我們在重症肌無力方面進行了一項進展非常順利的試驗。所以我們並沒有放棄第三代C5。我們也在探索因素 D。正如我在腳本中所描述的，我們有 3 個因素 D，每個因素在發展勢頭上的定位都略有不同。

Thanks, Marc.

謝謝，馬克。

So James, there are 2 parts to your question, as I understand it, the first is around the sources of growth that sit within the Imfinzi number. And then the second is really the durability of that growth. On the first piece, I'm really pleased to say that the growth is coming from multiple areas for Imfinzi and Imjudo. We see across geographies and also across indications that the performance was really driven for the quarter. Maybe to start first. And importantly, we do see, albeit a minority still an important part of the growth coming from the existing indications. So PACIFIC has strengthened, CASPIAN continues to grow across the globe as we work against it. The lion's share of the growth has come from new indications. TOPAZ-1 being the most significant of those. And we've seen really brisk uptake across U.S., Japan, Europe. HIMALAYA is also growing and continuing to grow nicely. And in fact, POSEIDON is an area where we're approved. So in the U.S. in particular, but also now getting underway in Japan. We're beginning to make inroads there as well.

所以詹姆斯，據我所知，你的問題分為兩部分，第一部分是關於 Imfinzi 數字中的增長來源。其次是增長的持久性。在第一篇文章中，我很高興地說 Imfinzi 和 Imjudo 的增長來自多個領域。我們看到各個地區以及各種跡象表明，本季度的業績確實受到了推動。也許先開始。重要的是，我們確實看到，儘管少數仍然是來自現有跡象的增長的重要部分。所以 PACIFIC 已經加強，CASPIAN 在我們對抗它的過程中繼續在全球範圍內發展。增長的絕大部分來自新適應症。 TOPAZ-1 是其中最重要的。我們已經看到美國、日本和歐洲的採用率非常高。 HIMALAYA 也在成長，並且會繼續成長得很好。事實上，POSEIDON 是我們獲得批准的領域。因此，尤其是在美國，但現在也在日本進行。我們也開始在那裡取得進展。

On your question specifically about Imjudo, just to share and to be helpful, Imjudo sales for the quarter were $37 million. And for last quarter, they were $15 million. So it's actually a minority of the $900 million in the quarter. So it's not a front-loaded Imjudo effect that you're seeing here. This really is Imfinzi TRxs that's driving this. And I expect us to continue to grow going forward. I do think we've probably got a little bit of bolus on TOPAZ-1, but I think all the other dimensions that I've described are ones that we expect to continue to move ahead.

關於你關於 Imjudo 的問題，只是為了分享和提供幫助，Imjudo 本季度的銷售額為 3700 萬美元。上個季度為 1500 萬美元。所以它實際上只是本季度 9 億美元的一小部分。所以這不是您在這裡看到的前加載 Imjudo 效果。這確實是 Imfinzi TRxs 推動的。我希望我們繼續向前發展。我確實認為我們可能在 TOPAZ-1 上得到了一些改進，但我認為我所描述的所有其他方面都是我們期望繼續前進的方面。

Thank you, Dave. Peter Welford, Jefferies.

謝謝你，戴夫。彼得韋爾福德，傑富瑞。

So I've got 2 R&D ones. Firstly, just looking at the tozorakimab, the many outlined the profile. Just wondering if you can give us any thoughts following the recent COPD data that we've had in biologics success there in terms of does that impact your thinking at all in development in this space and equally more broadly, biologics in COPD, and actually just outlined the population in particular, you're looking at in the tozorakimab COPD Phase III study and how that differs? And then secondly, on Farxiga combos. I know this comes up every quarter, but can you just give us an update if there is any data you have for both, I guess, the (inaudible) that's in-house and also the ERA and your latest thinking in terms of where we may see those programs move into Phase III?

所以我有 2 個研發人員。首先，只看 tozorakimab，許多人概述了概況。只是想知道您是否可以根據最近我們在生物製劑方面取得的成功的 COPD 數據給我們任何想法，這是否會影響您在這個領域的發展以及同樣更廣泛的 COPD 生物製劑方面的想法，實際上只是特別概述了人群，您正在查看 tozorakimab COPD III 期研究，這有何不同？其次，在 Farxiga 連擊上。我知道每個季度都會出現這種情況，但是如果您有任何數據，我想您能不能給我們一個更新，我想，內部的（聽不清）以及 ERA 和您對我們在哪裡的最新想法可能會看到這些項目進入第三階段？

So the first question on tozo and COPD programs. I mean, I think overall, and I think I said this in the last quarter, I'm encouraged to see a molecule -- a biologic molecule work in COPD because I think it sort of gives us confidence that actually the programs we have with Fasenra with tozo, hopefully, with our TSLP molecules as well will ultimately be positive. I think in terms of -- obviously, we need to see the Phase II data from our Phase II studies that are running with tozo, although we've obviously started Phase III as well based on some of the data we've already seen. But I think I would say our comment is high. The profile of the patients that we have in our NTL33 program, looking at both smokers and former smokers and current smokers. People with more than 2 exacerbations and ultimately will be held defined by the Phase II study that's reading out.

所以關於 tozo 和 COPD 計劃的第一個問題。我的意思是，我認為總的來說，我想我在上個季度說過這個，我很高興看到一個分子——一個生物分子在 COPD 中起作用，因為我認為它讓我們有信心，實際上我們擁有的項目Fasenra 與 tozo，希望與我們的 TSLP 分子一起最終是積極的。我認為 - 顯然，我們需要從與 tozo 一起運行的 II 期研究中查看 II 期數據，儘管我們顯然已經根據我們已經看到的一些數據開始了 III 期。但我想我會說我們的評論很高。我們的 NTL33 計劃中的患者概況，包括吸煙者、曾經吸煙者和現在吸煙者。急性加重超過 2 次並最終將由正在宣讀的 II 期研究定義的患者進行治療。

For the Fasenra program in COPD, which is the most advanced program we have, we're basing it off our 2 failed Phase III programs. And that's in patients that have had exacerbations, again, 3 or more exacerbations and also have high eosinophil counts. So overall, I think I'm more optimistic now that I've seen a program work in the biologics space, but ultimately, it will be determined by readouts from our data.

對於 COPD 中的 Fasenra 項目，這是我們擁有的最先進的項目，我們將其基於我們 2 個失敗的 III 期項目。這是在有過加重的患者中，再次，3 次或更多次加重並且嗜酸性粒細胞計數也很高。所以總的來說，我認為我現在更樂觀了，因為我已經看到了生物製劑領域的一個項目，但最終，這將取決於我們數據的讀數。

Farxiga combo?

法西加組合？

Farxiga combos, again, I think the Phase II data is moving well, I can't talk about it too much because we haven't announced the data. But I would say we're very much still on track both in terms of the ZiBo DAPA program, the MR program and bactostat as a monotherapy but also in combination and hopefully, during the course of the year, we'll be able to talk about the Phase III investment decisions, but it's a little bit too soon yet to talk about data specifically, but I would say they still on track in terms of our expectations for Phase III IDs and launches.

Farxiga 連擊，我認為第二階段的數據進展順利，我不能說太多，因為我們還沒有公佈數據。但我要說的是，無論是 ZiBo DAPA 項目、MR 項目和 bactostat 作為單一療法，還是聯合療法，我們都非常走上正軌，希望在這一年中，我們能夠討論關於 III 期投資決策，但現在具體談論數據還為時過早，但我想說，就我們對 III 期 ID 和啟動的預期而言，它們仍在軌道上。

Thank you, Mene. And then ultimately, Peter, the objective is really to develop a portfolio of combinations that will address different patient segments and complement each other and cover the whole field very well. But of course, this is still depending on a series of data sets.

謝謝你，梅內。最後，彼得，我們的目標實際上是開發一個組合組合，以解決不同的患者群體並相互補充並很好地覆蓋整個領域。不過當然，這還是要靠一系列的數據集。

Emily Field at Barclays.

巴克萊銀行的艾米麗菲爾德。

Yes, 2 questions from me. One, just you mentioned on Tagrisso, one of the drivers this quarter was improved duration of therapy for FLAURA. I was just wondering if you could provide more color around that as we're getting asked a lot, particularly ahead of whenever we may see MARIPOSA. And then just -- in adjuvant. I know the design of CAMBRIA-1 does allow for prior CDK4/6 for 2 years, but does a potential change in adjuvant standard of care, we'll see at ASCO change your thinking about that study or just any thoughts on adjuvant there?

是的，我有 2 個問題。第一，正如您在 Tagrisso 上提到的，本季度的驅動因素之一是 FLAURA 的治療持續時間有所延長。我只是想知道您是否可以提供更多顏色，因為我們經常被問到，特別是在我們可能看到 MARIPOSA 之前。然後只是 - 在佐劑中。我知道 CAMBRIA-1 的設計確實允許之前的 CDK4/6 進行 2 年，但輔助治療標準是否有潛在變化，我們將在 ASCO 上看到改變您對該研究的想法或只是對輔助治療的任何想法？

Dave, do you want to take the first one and Susan the second one.

戴夫，你想選第一個，蘇珊選第二個嗎？

Yes. So in terms of Emily, the duration of therapy that we're seeing in the real-world context. In the U.S. and in Europe, we are seeing it longer than the median PFSs and DOT that we saw in ADAURA. So Obviously, that was in the high 18s. I would say that we're now sort of seeing it depending upon where we are, somewhere between kind of 21 and 24 and the exactness of that is to be determined. But I think to the point that you're making, it's obviously quite relevant as we think about how clinicians see the efficacy that they get from monotherapy Tagrisso. And it's something that I've commented on in past quarters that certainly the efficacy that's coming through the monotherapy together with the tolerability is what gives us confidence that monotherapy is going to continue to be the first choice for many patients based upon that DOT that we're seeing in the real work from FLAURA.

是的。因此，就艾米麗而言，我們在現實世界中看到的治療持續時間。在美國和歐洲，我們看到它比我們在 ADAURA 中看到的 PFS 和 DOT 中值更長。很明顯，那是在 18 多歲的時候。我會說我們現在看到它取決於我們所處的位置，介於 21 和 24 之間，其準確性有待確定。但我認為就你所說的而言，這顯然與我們考慮臨床醫生如何看待他們從單一療法 Tagrisso 中獲得的療效非常相關。這是我在過去幾個季度評論過的事情，肯定是通過單藥療法帶來的療效和耐受性讓我們相信單藥療法將繼續成為基於我們 DOT 的許多患者的首選在 FLAURA 的真實作品中看到。

So thanks for the question about camizestrant. So the CAMBRIA-1 study is designed to capture that patient population that have had 2 to 5 years of adjuvant endocrine therapy with or without a CDK4/6 inhibitor. So the reinforcement of the benefit that you see of a CDK4/6 inhibitor in the adjuvant setting, I think, actually, makes this trial even more relevant because there are patients that can benefit from extended adjucant therapy in adjuvant setting. And these are patients with intermediate or high-risk of recurrence. So I think the changes in the adjuvant setting are in line with our expectations. And of course, CAMBRIA-1 does allow for both (inaudible).

所以感謝關於 camizestrant 的問題。因此，CAMBRIA-1 研究旨在捕獲接受過 2 至 5 年輔助內分泌治療（有或沒有 CDK4/6 抑製劑）的患者群體。因此，我認為，您在輔助環境中看到的 CDK4/6 抑製劑的益處得到加強，實際上使該試驗更具相關性，因為有些患者可以從輔助環境中的延長輔助治療中獲益。這些是中度或高複發風險的患者。所以我覺得輔助設定的變化是符合我們預期的。當然，CAMBRIA-1 確實允許兩者（聽不清）。

Thank you, Susan. Andrew Baum, at Citi. Andrew.

謝謝你，蘇珊。安德魯鮑姆，在花旗。安德魯。

Question for Mene and then one for Susan. So for Mene, you have been at asteric oral PCSK9 inhibitor that doesn't have a food interaction, which differentiates itself from Merck's agent. You have got an open-label Phase II trials, you're seeing data, but it's very difficult to find any published clinical data, including your patents of indications of efficacy of LDL lowering, just to give some sense of contrast versus both Repatha Praluent, but also Merck's data. So perhaps you could share with us, given you have highlighted it. I know you're excited about the product. Given the data that you have seen animal as well as human. Are you comfortable that it's going to deliver efficacy in a similar ballpark to the Praluent Repatha and Merck at least in terms of LDL lowering? So that's the first question.

問梅內，然後問蘇珊。因此，對於 Mene，您一直在使用沒有食物相互作用的星狀口服 PCSK9 抑製劑，這與默克公司的代理不同。你有一個開放標籤的 II 期試驗，你看到了數據，但很難找到任何已發表的臨床數據，包括你的低密度脂蛋白降低功效適應症的專利，只是為了與 Repatha Praluent 進行一些對比，還有默克公司的數據。所以也許你可以與我們分享，因為你已經強調了它。我知道你對這個產品很興奮。鑑於您已經看到動物和人類的數據。您是否認為它至少在 LDL 降低方面與 Praluent Repatha 和 Merck 具有相似的療效？這是第一個問題。

And then the second question to Susan. PARP inhibitors are absent from your lung cancer domination master plan. I'm just curious whether this is because you're concerned about toxicity and combining with TOPAZ inhibitors, whether you think that the efficacy doesn't have a strong enough rationale or there's something else I might be missing here?

然後是蘇珊的第二個問題。您的肺癌控制總體規劃中沒有 PARP 抑製劑。我只是好奇這是否是因為您擔心毒性並與 TOPAZ 抑製劑結合使用，您是否認為療效沒有足夠強大的理由或者我可能在這裡遺漏了什麼？

So I'll show you first little pieces -- it's a great question. And we're being somewhat cagey, I think, on purpose because obviously, it is a very competitive space, Andrew. So am I confident that we're going to have a target product profile that's competitive? What I'll say is that we've given ourselves like we did actually for the injectable PCSK9, I think a tough threshold for what we would take forward into more expensive late-stage studies. And so that's the profile we need to hit. I'm hoping we're going to get there. I'd like to see a few more patients dosed. I'm encouraged by what I'm seeing, but I won't get too excited yet until we've seen a bit more patient data. And of course, when we have then we'll be able to share it more broadly. But I think it looks encouraging, but I wouldn't -- it's not a home run yet.

因此，我將向您展示第一部分——這是一個很好的問題。我認為，我們是故意保持謹慎的，因為顯然，這是一個競爭非常激烈的領域，安德魯。那麼我是否有信心我們將擁有具有競爭力的目標產品概況？我要說的是，我們已經像我們實際為可注射 PCSK9 所做的那樣給了自己，我認為對於我們將進入更昂貴的後期研究的內容來說，這是一個艱難的門檻。這就是我們需要達到的目標。我希望我們能到達那裡。我希望看到更多的患者服用藥物。我對我所看到的感到鼓舞，但在我們看到更多患者數據之前我不會太興奮。當然，當我們擁有時，我們將能夠更廣泛地分享它。但我認為這看起來令人鼓舞，但我不會——這還不是本壘打。

So thanks for the question about PARP inhibitors in non-small cell lung cancer. So there are a subset of lung cancer patients that have mutations in HRR genes that may have increased sensitivity to PARP inhibition. We're awaiting the readout of studies that looking at the combination of PARP inhibition plus therapy. And we're also in dose escalation in combination with ADCs in a number of the trials. So I think it just reflects the -- the map that you see is as we see that evolution with the things that we currently have in hand are ready to move into Phase III or close to Phase III. Then of course, we anticipate that the standards of care can continue to evolve as data evolves.

感謝您提出有關非小細胞肺癌中 PARP 抑製劑的問題。因此，有一部分肺癌患者的 HRR 基因發生突變，可能對 PARP 抑制的敏感性增加。我們正在等待著眼於 PARP 抑制與治療相結合的研究的結果。在許多試驗中，我們還在與 ADC 聯合進行劑量遞增。所以我認為它只是反映了 - 你看到的地圖就像我們看到的那樣，我們目前手頭的東西已經準備好進入第三階段或接近第三階段。當然，我們預計護理標準會隨著數據的發展而不斷發展。

Thank you, Susan. Tim Anderson at Wolfe. Over to you, Tim.

謝謝你，蘇珊。沃爾夫的蒂姆安德森。交給你了，蒂姆。

On Tagrisso, usually maintains that Tagrisso monotherapy, like to remain the backbone for most patients in frontline lung, yet you started this small combination study with (inaudible) in frontline. So can you talk about the rationale behind that? And why start that when we recently, why wouldn't you have started that many months ago even all the way back in 2022? What was the trigger? And why such a small size trial? Is that so you can quickly advance it into a larger Phase III? And then just on Dato-DXd are you as confident as ever ahead of the readout of TROPION-Lung01?

在 Tagrisso 上，通常認為 Tagrisso 單一療法，喜歡保持一線肺部大多數患者的支柱，但你在一線開始了這項小型聯合研究（聽不清）。那麼你能談談這背後的理由嗎？為什麼我們最近才開始，你為什麼不在幾個月前就開始，甚至早在 2022 年就開始了？觸發因素是什麼？為什麼要進行如此小規模的試驗？這樣你就可以快速將其推進到更大的第三階段嗎？然後就在 Dato-DXd 上，您在 TROPION-Lung01 讀數之前是否像以往一樣自信？

Okay. Dave, you take the first one and Susan second one.

好的。戴夫，你選第一個，蘇珊選第二個。

Yes. So Tim, I just -- again, to ground on our view for the EGFR mutated space, we see Tagrisso clearly as the backbone of therapy for all patients being treated for EGFR mutated within, obviously, our labeled indication. And we think the majority are mono. But we've also made really clear that we do know that there is a desire to treat some patients with combination therapy and really here we see FLAURA2 as being, hopefully, if the results in the Phase III look like those from Opel appropriate for a certain subset of patients.

是的。所以蒂姆，我只是 - 再次基於我們對 EGFR 突變空間的看法，我們清楚地看到 Tagrisso 是所有接受 EGFR 突變治療的患者的治療支柱，顯然，我們標記的適應症。我們認為大多數是單聲道。但我們也非常清楚地表明，我們確實知道有一些患者希望通過聯合療法進行治療，而且我們確實在這裡看到了 FLAURA2，如果 III 期的結果看起來像歐寶的結果，那麼我們希望它適合某些患者子集。

We also have acknowledged and seen that as the CHRYSALIS data and the MARIPOSA data were unfolding, that there may indeed be a role for some subset of patients to be treated with the amivantamab combo. It's within that context that we've initiated the study that you described. It's called OSTARA. It's a nonregistrational medical affairs led study. It's a relatively small practice-informing study as opposed to something with registrational intent, really trying to answer questions for those who might have it down the road around the safety and the combinability of Tagrisso and amivantamab in the future if there was a physician who was interested in that. So I would say that this isn't in any way a departure from the view that we've got on Tagrisso, it is an additive component to a belief that Tagrisso is the backbone of therapy moving forward.

我們也承認並看到，隨著 CHRYSALIS 數據和 MARIPOSA 數據的展開，某些患者子集可能確實可以使用 amivantamab 組合進行治療。正是在這種背景下，我們啟動了您描述的研究。它叫做 OSTARA。這是一項非註冊醫療事務主導的研究。這是一項相對較小的實踐通知研究，而不是具有註冊意圖的研究，真正試圖回答那些可能在未來圍繞 Tagrisso 和 amivantamab 的安全性和可組合性的人的問題，如果有醫生的話對此感興趣。所以我想說，這絕不偏離我們對 Tagrisso 的看法，它是對 Tagrisso 是治療向前發展的支柱這一信念的補充組成部分。

Okay. And in terms of Dato-DXd, the risk of being booing, I want to be entirely consistent with what we said before, which is that the profile that we have for Dato-DXd, we're confident about based on the design of the ADC with the linker warhead combination. And the Dato in lung cancer, in particular, from the data from the Phase I study, which is not just showing a response rate in later lung cancer patients, but the durability of response is what gives us confidence in the ability to beat the standard of care in the second-line study. But we run Phase III trials in order to get the results, and we're eagerly awaiting the results of the TROPION-Lung01 as is everybody on the call.

好的。就 Dato-DXd 而言，被噓的風險，我想與我們之前所說的完全一致，即我們對 Dato-DXd 的配置文件，我們有信心基於設計ADC與連接器彈頭組合。肺癌方面的拿督，特別是從 I 期研究的數據來看，這不僅顯示了晚期肺癌患者的反應率，而且反應的持久性讓我們有信心超越標準二線研究中的護理。但是我們進行了 III 期試驗以獲得結果，並且我們和每個人都在熱切地等待 TROPION-Lung01 的結果。

Thanks, Susan. Simon Baker, Redburn, over to you, Simon.

謝謝，蘇珊。 Simon Baker，Redburn，輪到你了，Simon。

Pascal, two questions, if I may. Firstly, on Dato, and apologies if I missed a comment on this. But the timing on TROPION-Breast01 to have accelerated quite significantly. I just wonder if there's anything you could comment on that? And also with Dato, there was a very interesting poster at AACR looking at resensitization in resistant cell lines, a specific example being Trephine 11 loss being resensitized with ATR inhibitors.

帕斯卡，兩個問題，如果可以的話。首先，關於拿督，如果我錯過了對此的評論，我深表歉意。但是 TROPION-Breast01 的時間已經大大加快了。我只是想知道您對此有何評論？還有 Dato，在 AACR 上有一張非常有趣的海報，研究抗性細胞系的再敏化，一個具體的例子是環鑽 11 丟失被 ATR 抑製劑重新敏化。

So I just wonder how that fits in with your clinical development programs and the potential that would open up for multiple treatment lines with Dato? And then secondly, changing your subject entirely, probably 1 for you, Pascal. I just wondered what your initial thoughts were on yesterday's proposals for pharma legislation reform proposed by the European Commission?

所以我只是想知道這如何適合您的臨床開發計劃以及與 Dato 一起開發多個治療線的潛力？然後其次，完全改變你的主題，可能 1 對你來說，Pascal。我只是想知道您對昨天歐盟委員會提出的醫藥立法改革提案的最初想法是什麼？

Susan, do you want to cover the first 2?

蘇珊，你想報導前兩個嗎？

Yes. So for TROPION-Breast01, I think we're delighted that the accrual for this trial was 6 months ahead of schedule, which I think just reflects the level of unmet need and the level of interest in the Dato program for this particular setting. So that's really the explanation for the acceleration. Thanks for spotting the data that we had at AACR. I do think the ATR combination is an interesting one. That's 1 of a number of different combinations that we're looking at with our ADC portfolio.

是的。因此，對於 TROPION-Breast01，我認為我們很高興該試驗的應計費用比計劃提前 6 個月，我認為這僅反映了未滿足的需求水平以及針對此特定設置的 Dato 計劃的興趣水平。這就是加速的真正解釋。感謝您發現我們在 AACR 獲得的數據。我確實認為 ATR 組合很有趣。這是我們正在研究的 ADC 產品組合中的多種不同組合之一。

Thanks, Susan. The European question, Simon. I mean, there are 2 parts to it. I think 1 part is really the sort of a long-term impact of something like this on Europe. And I think really that -- as it relates to Europe, I mean this is the wrong response to an important issue. And the issue is access to medicines in Europe. And we know that Europe has been behind the U.S. in terms of access. But quite frankly, it's also falling behind Japan and it rapidly falling behind China as well. And that has been associated with, Europe also falling behind the U.S., but now also China in terms of clinical trials and emergence of biotechs.

謝謝，蘇珊。歐洲問題，西蒙。我的意思是，它有兩個部分。我認為其中一部分確實是此類事件對歐洲的長期影響。我真的認為——因為它與歐洲有關，我的意思是這是對一個重要問題的錯誤反應。問題是在歐洲獲得藥品。我們知道歐洲在准入方面一直落後於美國。但坦率地說，它也在落後於日本，而且也在迅速落後於中國。這與歐洲在臨床試驗和生物技術的出現方面也落後於美國有關，但現在也落後於中國。

I mean the -- I was in China the last couple of weeks. And you can see the innovation is really impressive in that country. So that's really -- this potential legislation is really not a good idea in terms of securing a strong life sciences sector in Europe. In terms of the impact on the industry and our company, it really is something that will evolve over because, first of all, it will take a couple of years for various stakeholders and participants to comment and discussions will take place. Nothing will be coming into a legislation for another 2 years. So in terms of commenting on the impact, I think it is a little bit early in details, and we should wait for the end result of this discussion and see what comes out of the legislation. But I guess, really, again, the sort of general underlying message that this kind of approach sends is that Europe is not really the most attractive place for the industry to invest in. And the reality is that there is an enormous amount of innovation in the U.S. to tap into we've all known that but is rapidly increasing, a very, very large amount of innovation in China, actually.

我的意思是——過去幾週我在中國。你可以看到那個國家的創新確實令人印象深刻。因此，就確保歐洲強大的生命科學行業而言，這項潛在立法確實不是一個好主意。就對行業和我們公司的影響而言，這確實會發生變化，因為首先，各利益相關者和參與者需要幾年的時間才能發表評論並進行討論。再過 2 年，什麼都不會進入立法。因此，就影響的評論而言，我認為現在細節還為時過早，我們應該等待這次討論的最終結果，看看立法會產生什麼結果。但我想，真的，再一次，這種方法發出的那種普遍的潛在信息是，歐洲並不是該行業真正投資的最具吸引力的地方。而現實是，歐洲有大量的創新美國利用我們都知道但正在迅速增加，實際上在中國有非常非常大量的創新。

So the next question is Mattias Häggblom at Handelsbanken. Mattias, over to you.

那麼下一個問題是 Handelsbanken 的 Mattias Häggblom。馬蒂亞斯，交給你了。

I have 2, please. So staying on China, which you touched upon in the previous question. I was just curious to hear a bit more on why you decided to bring it up in the CEO statement in this report, emphasizing the growth in pace of innovation if it was something in particular that made it sensible to bring up in this quarter and not earlier? And then secondly, I'm curious to understand if there is more color to provide on the decision to terminate Alexion 1840. Marc mentioned it on the call. I know that regulators asked for 2 mechanistic stats was the outcome of those the final piece. And does this, to an extent, change the character of what rare disease assets that would interest AstraZeneca going forward.

我有 2 個。所以留在中國，你在上一個問題中提到過。我只是想听聽更多關於您為什麼決定在本報告的 CEO 聲明中提出它的原因，強調創新步伐的增長，如果這特別使得在本季度提出而不是明智的話更早？其次，我很想知道終止 Alexion 1840 的決定是否有更多顏色可以提供。馬克在電話中提到了它。我知道監管機構要求 2 個機械統計數據是最後一塊的結果。這是否在一定程度上改變了阿斯利康未來感興趣的罕見疾病資產的特徵。

So thanks, Mattias. I'll take the first one, and I'll ask also Leon to jump in. And Marc, maybe you want to take the Wilson termination question. The reason I've brought it up is that I really think that we wanted to signal that China is back. I mean the economy is bouncing back. The government is very focused on what they call high-quality growth. Science and Innovation is 1 of their priorities across all sorts of industrial sectors, of course, not only life sciences. They're focused on a green development. They're focused on collaboration and they really are implementing a very impressive program in terms of stimulating economy and driving innovation. And that plays into a whole series of new innovative technologies and products that are coming out of the biotech sector. So we wanted to signal this because, first of all, China is an important market, of course. And then it's also not only an important market in terms of helping patients and driving growth, but it's also an important market in terms of tapping into innovation.

所以謝謝，馬蒂亞斯。我會回答第一個問題，我還會請 Leon 加入。Marc，也許你想回答 Wilson 終止問題。我之所以提出來，是因為我真的認為我們想發出中國回來的信號。我的意思是經濟正在反彈。政府非常關注他們所謂的高質量增長。科學和創新是他們在各種工業部門的優先事項之一，當然，不僅僅是生命科學。他們專注於綠色發展。他們專注於合作，他們確實在刺激經濟和推動創新方面實施了一項非常令人印象深刻的計劃。這對來自生物技術領域的一系列新的創新技術和產品產生了影響。所以我們想表達這一點，因為首先，中國當然是一個重要的市場。然後它不僅在幫助患者和推動增長方面是一個重要的市場，而且在利用創新方面也是一個重要的市場。

Leon can talk about this, and maybe also Susan could comment on some of the deals we did, and Susan was also in China for a couple of weeks. So both came back. They're definitely impressed with the progress that has been made in this country. And the last reason I wanted to signal it is that it plays to our strength as company. We are the largest pharma company in China. We have a tremendous team, and really positions us very well to benefit from everything that's happening in that country. Leon, do you want to sort of comment and maybe you could also comment on some of the things we are doing across China and the various headquarters, et cetera.

Leon 可以談談這個，也許 Susan 也可以對我們所做的一些交易發表評論，Susan 也在中國待了幾週。於是兩人都回來了。他們肯定對這個國家取得的進步印象深刻。我想表明的最後一個原因是它發揮了我們作為公司的優勢。我們是中國最大的製藥公司。我們擁有一支強大的團隊，確實使我們處於非常有利的位置，可以從該國發生的一切中受益。 Leon，你想發表評論嗎，也許你也可以評論我們在中國和各個總部等地方所做的一些事情。

Yes. I think before I comment on China, I think emerging market is overall quite exciting and China is about 14%, 15%. And outside the China emerging markets are growing much faster, also 14%, 15%. So it's really worth looking at. And within China, I think we are #1 company with a quite solid position. And we actually speed up our global import product portfolio rapidly to benefit the Chinese patients. So this year, we have incur to and also Calquence and also we launched our rare disease portfolio. So all these things are very exciting for imported portfolio.

是的。我想在我評論中國之前，我認為新興市場總體上非常令人興奮，中國大約佔 14%、15%。而中國以外的新興市場增長更快，分別為 14%、15%。所以真的很值得一看。在中國，我認為我們是排名第一的公司，地位相當穩固。我們實際上正在迅速加快我們的全球進口產品組合，以造福中國患者。所以今年，我們招致了 Calquence，我們還推出了罕見病產品組合。所以所有這些對於進口作品集來說都是非常令人興奮的。

And also, we have a USD 1 billion fund, venture fund, investing into companies we are familiar and also an attractive, I think, Susan, and Mene's global research team are helping us to identify interesting targets to invest. So -- and plus we are also closely working with many China rising start-up companies. And we -- like we work with HUTCHMED developing their C MET, savolitinib and also as a starting point. And in the future, I mean, Susan's team also signed several deals in cell therapy and also in Claudin-18.2. And also, we hope also to tap into the non-oncology rising innovation in China. So I think China innovation as Pascal put it in the past 2, 3 weeks, we traveled across meeting a lot of interesting start-up companies. And it is really exploding. So we hope instead of watching, I think we are a leading company in China. So we should benefit from rising innovation in China who make this innovation also accessible to the patients outside China.

而且，我們有一個 10 億美元的基金，風險基金，投資於我們熟悉的公司，我認為還有一個有吸引力的公司，Susan 和 Mene 的全球研究團隊正在幫助我們確定有趣的投資目標。所以——此外，我們還與許多中國新興的初創公司密切合作。我們 - 就像我們與 HUTCHMED 合作開發他們的 C MET，savolitinib 一樣，也是一個起點。在未來，我的意思是，Susan 的團隊還在細胞療法和 Claudin-18.2 方面簽署了幾項協議。此外，我們還希望利用中國非腫瘤領域的新興創新。所以我認為中國創新正如 Pascal 所說，在過去的 2、3 周里，我們遇到了很多有趣的初創公司。而且真的很爆炸。所以我們希望而不是觀望，我認為我們是中國領先的公司。因此，我們應該受益於中國不斷興起的創新，這些創新使中國以外的患者也可以使用這種創新。

So thanks, Leon. Just a couple of comments on the deals that we've done. So as you said, building on the relationship we've had with Hutchison MediPharma for savolitinib, we've done 3 deals in the last 12 months with Cellular Biomedicine Group for the cell therapy asset where they're helping by running the investigator-initiated trial with our GPC3 constructs, and this actually helps us accelerate that program and gain clinical experience faster than we could otherwise.

所以謝謝，萊昂。就我們已經完成的交易發表一些評論。正如您所說，基於我們與 Hutchison MediPharma 就 savolitinib 建立的關係，我們在過去 12 個月內與 Cellular Biomedicine Group 就細胞治療資產完成了 3 筆交易，他們通過運行研究人員發起的項目來提供幫助使用我們的 GPC3 結構進行試驗，這實際上有助於我們加快該計劃並比其他方式更快地獲得臨床經驗。

We also have done a deal with Harbour Biomed for a T cell engager targeting Claudin-18.2, which is an important target on gastric and pancreatic cancer. And then with KeyMed access to an antibody drug conjugate with an MMA warhead, again, targeting Claudin-18.2. So I do think, as Pascal said, we come back from China excited and energized by the interactions that we've got there, the level of innovation and the science, the quality, the number of companies that are starting up in that space. It's very exciting. And the quality of the investigators that you can work with is also really good. So I think it is an opportunity for us to leverage our position there and help us to actually not just think about China delivering for China, but China innovation delivering for globally relevant indications and accelerating that. So I think that's the opportunity that's there to be had.

我們還與 Harbour Biomed 就針對 Claudin-18.2 的 T 細胞接合器達成協議，這是胃癌和胰腺癌的重要靶標。然後通過 KeyMed 獲得帶有 MMA 彈頭的抗體藥物偶聯物，再次針對 Claudin-18.2。所以我確實認為，正如帕斯卡所說，我們從中國回來時對我們在那裡的互動、創新水平和科學、質量以及在該領域初創公司的數量感到興奮和充滿活力。這是非常令人興奮。您可以與之合作的調查人員的素質也非常好。因此，我認為這對我們來說是一個機會，可以利用我們在那裡的地位，幫助我們實際上不僅僅是考慮中國為中國提供服務，而是中國創新為全球相關的適應症提供服務並加速這一進程。所以我認為這是一個機會。

Thanks, Susan. Marc?

謝謝，蘇珊。馬克？

First of all, let me remind you of the reason why Alexion invested in 1940, Wilson disease is a disease with an extremely high medical need where no innovation has taken place for decades beyond the copper chelator. So this is why, Alexion, you invested in it. Regarding the recent decision that we made, it's basically a case of looking at the totality of data and also a close interaction with regulators. The Phase III that we produced in 2021 produced positive results. But then we conducted, as you mentioned, 2 mechanistic study whose results were less clear. So when you look at the overall -- the totality of the data, it was not possible for us to demonstrate clearly benefit risk for the Wilson population, and then we decided to discontinue.

首先提醒大家一下Alexion在1940年投資的原因，Wilson病是一種醫療需求極高的疾病，幾十年來除了銅螯合劑沒有創新。所以這就是為什麼，Alexion，你投資它。關於我們最近做出的決定，這基本上是一個查看數據整體以及與監管機構密切互動的案例。我們在 2021 年生產的第三階段取得了積極成果。但正如您所提到的，我們隨後進行了 2 項機械研究，其結果不太清楚。因此，當您查看整體數據時，我們無法清楚地證明威爾遜人群的受益風險，然後我們決定停止。

Thank you, Marc. James Quigley at Morgan Stanley. You may go ahead, James.

謝謝你，馬克。摩根士丹利的詹姆斯奎格利。你可以繼續，詹姆斯。

It's Mark Purcell from Morgan Stanley. Apologies, with the mix up. Two questions. Firstly, Pascal, could you help us understand and put into context the PanTumor opportunity for Enhertu? So firstly, the sort of probability and breadth of the PanTumor approval you may get for the PanTumor02 trial, plans to move into earlier lines. And then the importance of the PanTumor01 trial in HER2 mutant cancer in terms of wrapping up a sort of broader opportunity there?

我是摩根士丹利的 Mark Purcell。抱歉，混淆了。兩個問題。首先，Pascal，你能幫助我們理解 PanTumor 對 Enhertu 的機會並將其放在背景中嗎？因此，首先，您可能獲得 PanTumor02 試驗的 PanTumor 批准的可能性和廣度，計劃進入更早的生產線。然後，在 HER2 突變癌症中的 PanTumor01 試驗在結束更廣泛的機會方面的重要性？

And then sort of secondly, the lung cancer on Slide 15 is super helpful. I just wondered, given the sort of progress of the investment that's been made in gastric and GI tumors, could you sort of provide us some perspective of where you're heading here? I sort of know as Susan just mentioned, the Claudin-18.2, ADC opportunities, obviously validated with the Astellas multiple antibody and response rates of over 75% and potential combination there. So the gastric opportunity, firstly, and then secondly, the colorectal cancer opportunity where the eGFR CM bi-specific ADC looks super exciting. So your thoughts there would be great.

其次，幻燈片 15 上的肺癌非常有幫助。我只是想知道，考慮到在胃和胃腸道腫瘤方面取得的投資進展，您能否向我們提供一些關於您將走向何方的觀點？正如 Susan 剛才提到的，我有點知道 Claudin-18.2，ADC 的機會，顯然已經通過 Astellas 多重抗體和超過 75% 的反應率以及那裡的潛在組合進行了驗證。因此，首先是胃癌機會，其次是結直腸癌機會，其中 eGFR CM 雙特異性 ADC 看起來非常令人興奮。所以你的想法會很棒。

Thanks so much. Susan, do you want to cover those?

非常感謝。蘇珊，你想報導這些嗎？

Okay. So thanks for the interest in PanTumor in HER2 data, which, as I said, are going to be shared at ASCO. So I think we probably have more detailed conversation there about that. Obviously, this is something we're going to need to discuss with regulatory authorities and there will be a question about the appropriate biomarker cutoff across different indications. So I think we are also, of course, looking at the HER2 mutant setting. There is an overlap between the HER2 mutation and HER2 overexpression of the HER2 mutant tumors that quite often highly overexpressing as well. But I think there will be data that we'll look at that, which I think helps support the data that we'll have from the Pan HER2 overexpressing segment.

好的。所以感謝 PanTumor 對 HER2 數據的興趣，正如我所說，這些數據將在 ASCO 上共享。所以我認為我們可能會就此進行更詳細的討論。顯然，這是我們需要與監管機構討論的事情，並且會有關於不同適應症的適當生物標誌物截止值的問題。所以我認為我們當然也在研究 HER2 突變體設置。 HER2 突變腫瘤的 HER2 突變和 HER2 過表達之間存在重疊，通常也高度過表達。但我認為我們會看到一些數據，我認為這有助於支持我們將從 Pan HER2 過度表達部分獲得的數據。

And then in terms of moving into GI cancers with the TOPAZ and HIMALAYA data that Dave has already referenced. I think we have a beachhead into these tumors with Imfinzi, but I think there is significant opportunity to improve on the current standard of care. And that's why we're excited about the Claudin-18.2 ADC asset there. Obviously, we're also looking at combinations of ADC plus IO agents across the portfolio. With regards to the eGFR bi-specific in colorectal cancer, yes, there is overexpression of both of these targets within colorectal cancer. I think we also have to look at the activity level in patients that have had prior to summarize inhibition in some of the GI tumors, which is something that is relevant. And of course, colorectal cancer often overexpresses membrane pumps that can pump out warhead. So I think we just need to see the clinical data in order to understand what the real potential is for these molecules. But you're right that this is an area of interest for us.

然後在使用 Dave 已經引用的 TOPAZ 和 HIMALAYA 數據進入 GI 癌症方面。我認為我們已經通過 Imfinzi 進入這些腫瘤的灘頭陣地，但我認為有很大的機會可以改善當前的護理標準。這就是為什麼我們對那裡的 Claudin-18.2 ADC 資產感到興奮。顯然，我們也在研究整個產品組合中 ADC 和 IO 代理的組合。關於結直腸癌中的 eGFR 雙特異性，是的，結直腸癌中這兩個靶點均有過表達。我認為我們還必須查看在某些 GI 腫瘤中具有總結抑製作用的患者的活動水平，這是相關的。當然，結直腸癌通常會過度表達可以泵出彈頭的膜泵。所以我認為我們只需要查看臨床數據即可了解這些分子的真正潛力。但你是對的，這是我們感興趣的領域。

Thank you, Susan. Seamus Fernandez, Guggenheim. Seamus, over to you.

謝謝你，蘇珊。 Seamus Fernandez，古根海姆。西莫，交給你了。

So really my only question is on fulvestrant. We saw some impressive data presented at the recent neuro meeting. Just hoping that you could comment on that. And also follow-up with the broader plans an opportunity that you see in the overall ATTR setting, particularly given your plans on the cardiac side and the overall competitive landscape?

所以我唯一的問題是氟維司群。我們在最近的神經會議上看到了一些令人印象深刻的數據。只是希望你能對此發表評論。還要跟進更廣泛的計劃，這是您在整體 ATTR 環境中看到的機會，特別是考慮到您在心臟方面的計劃和整體競爭格局？

Thank you so much. Mene, do you want to cover it from R&D? And finally maybe Ruud could jump in and also give a sense of the potential.

太感謝了。 Mene，你想從研發中覆蓋它嗎？最後，也許 Ruud 可以加入進來，也能給人一種潛力的感覺。

So I think we were particularly pleased with the functional data in terms of the quality of life because we continue to see an improvement, which I think is -- looks, I think, quite compelling. And obviously, I think the data that we've seen now on the consistency of our data gives us more confidence given the mechanism this is going to work well in cardiomyopathy as well. So I think overall, we're very pleased. We're excited with the submission on the filing in polyneuropathy and waiting with anticipation for the cardiomyopathy data at the moment. Ruud?

所以我認為我們對生活質量方面的功能數據特別滿意，因為我們繼續看到改善，我認為這看起來非常引人注目。顯然，我認為我們現在看到的關於數據一致性的數據讓我們更有信心，因為這在心肌病中也能很好地發揮作用。所以我認為總的來說，我們非常高興。我們對多發性神經病備案的提交感到興奮，並期待著目前的心肌病數據。魯德？

Yes. So a little bit the scoping of the opportunity, there are roughly 40,000 patients with ATTR-PM. So it's a relatively small population, but there's a very large overlap with the main indication in cardiomyopathy. As we have announced, the FDA has accepted our filing and we are expecting, hopefully, a positive outcome in the second half of this year, and the team in the United States is working, of course, on the prelaunch activities. And equally, we are preparing ourselves for the CM indication, the much larger indication. Roughly there are between 300,000 and 500,000 patients worldwide with the CM, but there's also a tremendous underdiagnosis in the CM. Most of those patients are detected very late in the disease state. Clearly, with our activities in the HFpEF indication with Farxiga, we are expecting that the diagnosis rate will at least double moving forward. So all in all, a very substantial population in order to promote our product in the CM category. Of course, that will be a little bit later. That will be after 2024. But all in all, all the lights at the moment are clearly green.

是的。所以稍微確定一下機會的範圍，大約有 40,000 名 ATTR-PM 患者。所以這是一個相對較小的人群，但與心肌病的主要適應症有很大的重疊。正如我們所宣布的那樣，FDA 已經接受了我們的申請，我們希望在今年下半年取得積極成果，當然，美國團隊正在開展上市前活動。同樣，我們正在為 CM 適應症做準備，這是一個更大的適應症。全世界大約有 300,000 至 500,000 名 CM 患者，但 CM 也存在巨大的漏診情況。這些患者中的大多數在疾病狀態很晚才被發現。顯然，隨著我們在 Farxiga 的 HFpEF 適應症方面的活動，我們預計診斷率將至少翻一番。因此，總而言之，為了在 CM 類別中推廣我們的產品，需要大量人口。當然，那會晚一點。那將是2024年之後。但總而言之，此刻所有的燈顯然都是綠色的。

Thanks, Ruud. Emmanuel Papadakis, Deutsche Bank.

謝謝，魯德。 Emmanuel Papadakis，德意志銀行。

Perhaps first 1 on PROpel ahead of the advisory review tomorrow. Any perspective you could give us on the FDA stance at a bit keen to potentially restrict approval to not just the HR and actually the BRCA subgroup patients. So I'd be interested to hear your thoughts on those documents and expectations into tomorrow. And then perhaps a question on FLAURA2 ahead of the imminent we do headline data perhaps you could help frame our expectations on PFS in light of the Opel data that was presented at ASCO last year where you saw a 70% PFS rate at 24 months. Should we be thinking of very high 20s median PFS is achievable? Or is the number radically different to that, either below or above also possible?

也許在明天的諮詢審查之前先在 PROpel 上發布 1。您可以向我們提供有關 FDA 立場的任何觀點，有點熱衷於可能限制批准不僅限於 HR，實際上還包括 BRCA 亞組患者。所以我很想听聽您對這些文件的看法以及對明天的期望。然後，也許在我們即將發布標題數據之前，有一個關於 FLAURA2 的問題，也許您可以根據去年在 ASCO 上展示的歐寶數據幫助構建我們對 PFS 的預期，您在 24 個月時看到了 70% 的 PFS 率。我們是否應該考慮可以實現非常高的 20s 中位 PFS？還是這個數字與那個數字完全不同，低於或高於這個數字也是可能的？

Thanks, Emmanuel. I think they are both for you, Susan. Very prepared as today as always.

謝謝，伊曼紐爾。我想它們都適合你，蘇珊。一如既往地準備得很充分。

Yes. So obviously, we'll know tomorrow the outcome of the PROpel ODAC. But I'd make three points. First of all, there was a mechanism of action for interaction of the androgen receptor, downstream signaling and olaparib. So AR is involved in DNA repair in AR-driven cells and actually depends on PARP1. So with the combination you get increased DNA damage selectively in AR-driven cells regardless of the BRCA status, and we have data to demonstrate that. So this is different from the monotherapy setting such as ovarian cancer late-line settings. And that difference in mechanism of action is reflected in the data from 3 randomized clinical trials, the Study 8 Phase II study, the PROpel study and TALAPRO-2, which recently read out, which all showed similar effects with strong benefit both in BRCA wild type as well as in BRCA mutant. This effect, however, is dependent on dose because it's dependent on the PARP chopping effect and hence, the difference, I think, with magnitude.

是的。很明顯，我們明天就會知道 PROpel ODAC 的結果。但我要提出三點。首先，存在雄激素受體、下游信號和奧拉帕尼相互作用的作用機制。因此，AR 參與了 AR 驅動細胞中的 DNA 修復，並且實際上依賴於 PARP1。因此，無論 BRCA 狀態如何，通過這種組合，您都會在 AR 驅動的細胞中選擇性地增加 DNA 損傷，我們有數據可以證明這一點。所以這不同於單藥治療設置，例如卵巢癌晚期設置。而這種作用機制的差異反映在 3 項隨機臨床試驗的數據中，即 Study 8 II 期研究、PROpel 研究和最近公佈的 TALAPRO-2，它們都顯示出相似的效果，並且在 BRCA 野生型中都具有很強的益處類型以及 BRCA 突變體。然而，這種效應取決於劑量，因為它取決於 PARP 斬波效應，因此，我認為，差異與幅度有關。

The second point I'd make is the effect size in the BRCA wild type cannot be explained by false-negative ctDNA testing. There's high agreement for the ctDNA and tissue testing at 94%. So if you look at the patients that are ctDNA negative and tissue undetermined, that's 226 patients in the PROpel study, only 6 could be effectively misclassified. This cannot explain the effect size. And third point is that the evidence does not support that there's an OS detriment, I think, identifying the double negative, both ctDNA and tissue-based negative as it is looking at a subgroup of a subgroup. And in fact, in the BRCA undetermined group, the OS hazard ratio is 0.71. So if you look at the totality of the data and the totality of the secondary endpoints, I think it supports a good benefit risk profile for olaparib in this patient population in combination with abiraterone. So that's our position. We'll represent that strongly at the ODAC tomorrow, and we look forward to seeing what the results of that are.

我要說的第二點是 BRCA 野生型的效應大小不能用假陰性 ctDNA 測試來解釋。 ctDNA 和組織檢測的一致性很高，達到 94%。因此，如果您查看 ctDNA 陰性且組織未確定的患者，即 PROpel 研究中的 226 名患者，只有 6 名可能被有效地錯誤分類。這無法解釋效果大小。第三點是證據不支持存在 OS 損害，我認為，確定雙重陰性，即 ctDNA 和基於組織的陰性，因為它正在研究一個亞組的一個亞組。事實上，在 BRCA 未確定組中，OS 風險比為 0.71。因此，如果您查看數據的整體性和次要終點的整體性，我認為它支持奧拉帕尼聯合阿比特龍在該患者人群中的良好獲益風險概況。這就是我們的立場。我們將在明天的 ODAC 上強烈代表這一點，我們期待看到結果。

In terms of FLAURA2, the Opel data that was published is in a reasonable size patient population about 60 patients. So I think it gives you a reasonable confidence about the limits of the medium PFS which in that study was 31 months. So I think that's the basis for assumption for FLAURA2, you can obviously get some, the question to the mean as you move from Phase II to Phase III, but I think we're confident in that effect size and the tolerability profile that we actually see for the combination. So I think this is going to be an important potential new opportunity for Tagrisso and represents a choice that then patients can have, not every patient will want a combination therapy, but I think it represents a potential opportunity for those patients with bulkier disease or the end-to-end perspective.

就 FLAURA2 而言，已發布的 Opel 數據是在一個合理規模的患者群體中，大約有 60 名患者。所以我認為它讓你對在該研究中為 31 個月的中等 PFS 的限制有合理的信心。所以我認為這是 FLAURA2 假設的基礎，當你從第二階段進入第三階段時，你顯然可以得到一些關於均值的問題，但我認為我們對我們實際的效果大小和耐受性概況充滿信心查看組合。所以我認為這對 Tagrisso 來說將是一個重要的潛在新機會，代表了患者可以做出的選擇，並不是每個患者都想要聯合治療，但我認為這代表了那些患有更大疾病或疾病的患者的潛在機會。端到端的觀點。

Thanks, Susan. Matthew Weston, Credit Suisse.

謝謝，蘇珊。瑞士信貸的馬修韋斯頓。

Two questions, if I can. The first is a follow-up on TROPION-Breast01. Susan, you mentioned that recruitment was 6 months ahead of expectations, but the readout has been brought forward, I think, nearly 18 months. So can you explain the difference? Is it that you've shifted the focus to the PFS endpoint or co-primary endpoint rather than OS? Any further commentary would be very helpful. And then secondly, a question on TROPION-Lung01 similar to the one we've just had on FLAURA2. We're all looking forward to that press release, and we're hoping that we're going to see that Astra favorite comment of clinically meaningful. Can someone on the call set out what clinically meaningful would be in your view so that we aren't surprised when we subsequently see the data?

兩個問題，如果可以的話。第一個是 TROPION-Breast01 的後續。蘇珊，你提到招聘比預期提前了 6 個月，但我認為讀數已經提前了將近 18 個月。那麼你能解釋一下區別嗎？您是否已將重點轉移到 PFS 終點或共同主要終點而不是 OS？任何進一步的評論都會非常有幫助。其次，關於 TROPION-Lung01 的問題類似於我們剛剛在 FLAURA2 上遇到的問題。我們都期待著那篇新聞稿，我們希望我們能看到 Astra 最喜歡的具有臨床意義的評論。電話中的某個人能否闡明您認為具有臨床意義的內容，以便我們在隨後看到數據時不會感到驚訝？

So thanks for the questions. To start with TROPION-Breast01, we have a dual primary endpoint of PFS and OS in this study. The endpoints haven't changed, but the rapid accrual just gives us the opportunity for that to be read out at an earlier point. And I think what we've guided before was beyond the end of this year versus now coming into this year. So I don't think it really is as big a shift in the time lines as you're indicating.

所以謝謝你的問題。從 TROPION-Breast01 開始，我們在本研究中有 PFS 和 OS 的雙重主要終點。端點沒有改變，但快速增長只是讓我們有機會在更早的時候讀出它。而且我認為我們之前的指導是在今年年底之後，而不是現在進入今年。所以我認為時間線的轉變並不像你所說的那麼大。

I think, Susan, maybe this is a good time to give yourself a pat on the back and your team because the recruitment has been incredibly fast, and the team has done a beautiful job. Yes.

我想，蘇珊，也許現在是表揚你自己和你的團隊的好時機，因為招聘速度非常快，而且團隊做得很好。是的。

Yes. Well, let me give all the credit to the team because they are the ones that have done the work. So Cristian Massacesi's team and Michele Sample, who's led the operations team have done a great job here. In terms of TROPION-Lung01, what we said before in terms of clinical meaningfulness, you're expecting -- if you look at the contact 1 data set, something in the range of 4 to 5 months median PFS for the control arm, I think, is a reasonable assumption. And it's well sized for a clinically meaningful benefit, which would probably be in the range of 2 to 3 months on that background. So I don't think that's changed either. So that answers your question.

是的。好吧，讓我把所有的功勞都歸功於團隊，因為他們是完成工作的人。因此，Cristian Massacesi 的團隊和領導運營團隊的 Michele Sample 在這裡做得很好。就 TROPION-Lung01 而言，我們之前在臨床意義方面所說的，你期望——如果你查看接觸 1 數據集，對照組的 PFS 中位數在 4 到 5 個月的範圍內，我認為，是一個合理的假設。而且它的規模非常適合具有臨床意義的益處，在這種背景下可能會在 2 到 3 個月的範圍內。所以我認為這也沒有改變。這樣就回答了你的問題。

Thank you. Luisa Hector, Berenberg.

謝謝。路易莎赫克托，貝倫貝格。

Thanks, Pascal. So maybe just a quick 1 again for Susan on when we might see the first response rate data for the internal ADCs that you highlighted? And then perhaps just if you can quantify in Q1 anything on price impact. There seem to be various movements, particularly European clawbacks were mentioned in the press release. So maybe split between U.S. and Europe, any impact on price and then stocking or gross to net impacts, which were also scattered throughout the press release?

謝謝，帕斯卡。那麼，關於我們什麼時候可以看到您強調的內部 ADC 的第一個響應率數據，蘇珊也許只是快速的 1？然後也許只是如果你能在第一季度量化任何對價格的影響。似乎有各種動向，特別是新聞稿中提到的歐洲回扣。因此，也許在美國和歐洲之間分開，對價格的任何影響，然後是庫存或毛對淨影響，這些影響也散佈在整個新聞稿中？

Thank you, Luisa. Susan, do you want to take the first one? And Ruud, you would take the second one. And if Dave, you want to step in, also, please do so, but maybe start with Ruud.

謝謝你，路易莎。蘇珊，你想要第一個嗎？而 Ruud，你會選擇第二個。如果戴夫，你也想介入，請這樣做，但也許從 Ruud 開始。

Yes, I would anticipate that we would share data probably next year for the early phase ADCs.

是的，我預計我們可能會在明年共享早期 ADC 的數據。

Okay. And regarding, Luisa, the clawbacks in itself in Europe specifically are not unusual. We are facing that year after year, it's our normal business practice, and we are just flagging at in order to provide a little bit more color to our business performance. That's also true in the United States. As you know, very well, of course, in the United States, we are negotiating our prices on an annual basis, and there are rebates and, of course, gross to net adjustments. And we -- at least in the foreseeable future, we expect to continue that. And of course, there is new legislation potentially coming on our way in the United States with the IRA. But all in all, currently, it's clearly business as usual.

好的。就 Luisa 而言，歐洲的回扣本身並不罕見。我們年復一年地面對，這是我們正常的商業行為，我們只是為了給我們的經營業績提供更多的色彩。在美國也是如此。正如你所知，當然，在美國，我們每年都在談判我們的價格，並且有回扣，當然還有毛額到淨額的調整。我們——至少在可預見的未來，我們希望繼續這樣做。當然，在美國，IRA 可能會出台新的立法。但總而言之，目前，它顯然一切如常。

I mean I think the only piece, Luisa, that I'd add to that is that I commented in my remarks on Calquence and Lynparza stocking in the quarter. I don't have much more to add, but that certainly was relevant for both of those brands. And then on price in the U.S. -- and while seeing that we took some price increases in line with what we thought was appropriate. But keep in mind that in the quarter, the impact of that is relatively negligible because you've got price protections that are in place for a lot of the distributors and the payers and the GPOs. Just to try to put a bit more color on your question.

我的意思是，我認為唯一要補充的一點是，路易莎，我在本季度對 Calquence 和 Lynparza 庫存的評論中發表了評論。我沒有更多要補充的，但這對這兩個品牌來說肯定是相關的。然後是美國的價格——同時看到我們根據我們認為合適的價格進行了一些上漲。但請記住，在本季度，這種影響相對可以忽略不計，因為你已經為許多分銷商、付款人和 GPO 提供了價格保護。只是想為您的問題添加更多色彩。

Michael Leuchten, UBS.

Michael Leuchten，瑞銀。

Two questions, please. Just going back to the speed of recruitment for both FLAURA2 and MARIPOSA. How do you square that with your view that monotherapy eGFR is going to be the standard of care if it has to be squared at all.? Just interested in you thought that both of these trials have recruited very, very quickly. And a quick question for Dave. What was the underlying growth for Lynparza in Q1 if you strip out the inventory work down that I presume, came out of the PROpel expectations.

請教兩個問題。回到 FLAURA2 和 MARIPOSA 的招募速度。您如何將其與您認為單藥治療 eGFR 將成為護理標準的觀點相結合？只是對您感興趣，認為這兩個試驗的招募速度都非常非常快。還有一個簡短的問題要問戴夫。如果你剔除我認為的庫存工作，第一季度 Lynparza 的潛在增長是多少，這是出於 PROpel 的預期。

I just want to clarify, TB01 is a breast cancer.

我只是想澄清一下，TB01 是一種乳腺癌。

FLAURA2 and MARIPOSA recruited fast and what does that mean in terms of physicians' interest in this indication -- in this combination?

FLAURA2 和 MARIPOSA 招募速度很快，就醫生對這種適應症的興趣而言，這意味著什麼——在這種組合中？

Right. Well, I mean, there are patients who will want even more benefit than can be achieved with monotherapy Tagrisso. But I'm just pointing out that if you look at the totality of patients that you're treating with eGFR mutant lung cancer, a lot of them elderly and oral monotherapy that they can take home is an attractive option. But if you're looking at patients that want to accrue clinical trial sites and academic centers, that's a different patient population and we're often looking for more options. So I think there's a large number of patients that have got first-line metastatic non-small cell lung cancer, it's a big indication. There's lots of opportunity to improve on the current standard of care.

正確的。好吧，我的意思是，有些患者希望獲得比單藥 Tagrisso 所能獲得的更多益處。但我只是指出，如果你看看你正在治療的 eGFR 突變肺癌患者的總數，他們中的很多人都是老年人，他們可以帶回家的口服單一療法是一個有吸引力的選擇。但是，如果你正在尋找想要積累臨床試驗地點和學術中心的患者，那是一個不同的患者群體，我們經常在尋找更多的選擇。所以我認為有大量患者患有一線轉移性非小細胞肺癌，這是一個很大的跡象。有很多機會可以改進當前的護理標準。

Dave, maybe you could comment on Lynparza but also from a commercial viewpoint? How do you see this FLAURA2 and MARIPOSA combination and physicians reactions to those?

戴夫，也許你可以從商業角度對 Lynparza 發表評論？您如何看待這種 FLAURA2 和 MARIPOSA 組合以及醫生對此的反應？

Absolutely. So on Lynparza, Michael, on a sequential first versus fourth quarter, on the global sales, we see growth across Europe in demand. We see growth in Rest of World also within international. In terms of within the U.S. right now, I would say the demand is relatively stable net of the stocking that we described, again, made comments on this. There is opportunity for us to continue to grow Lynparza. Some of these opportunities are more challenging. It's about driving testing rates in ovarian in the HRD population. It's about really creating even further imperative and driving testing for BRCA in breast cancer among hormone receptor positive patients, where the unmet need and -- or the perceived unmet need is not quite the same as it is in triple negative.

絕對地。因此，在 Lynparza 上，邁克爾在第一季度與第四季度的連續全球銷售中，我們看到整個歐洲的需求都在增長。我們看到世界其他地區的增長也在國際範圍內。就美國目前而言，我想說的是，扣除我們描述的庫存後，需求相對穩定，再次對此發表評論。我們有機會繼續發展 Lynparza。其中一些機會更具挑戰性。這是關於在 HRD 人群中駕駛卵巢測試率。這是關於在激素受體陽性患者中真正創造更進一步的必要和驅動測試 BRCA 的乳腺癌，其中未滿足的需求和 - 或者感知的未滿足的需求與三重陰性不完全相同。

Transitioning, again, just to go to Pascal's question to me around the opportunity for FLAURA2, we know that there are certain patients with presentation of more aggressive disease. We also know that certainly, if we're able to replicate the PFS results and the response rates of nearly 90% that we see in Opel along with the PFS of 31 months that we are seeing within Opel that there will be a subset of patients for whom that combination is something that physicians may very well want to be utilizing.

再次過渡到 Pascal 關於 FLAURA2 機會的問題，我們知道有些患者表現出更具侵襲性的疾病。我們當然也知道，如果我們能夠複製我們在歐寶中看到的 PFS 結果和近 90% 的響應率以及我們在歐寶中看到的 31 個月的 PFS，那麼將會有一部分患者對於他們來說，這種組合是醫生可能非常希望使用的東西。

And so as Susan said, while we believe that the majority of patients will be seen as most appropriate for monotherapy because it's oral because we're getting good approaching 2 years PFS and because the side effect profile is well understood for certain patients where the disease appears more aggressive, getting that response rate using FLAURA2 will be seen as attractive. And I think that, that could translate into further growth in terms of duration of therapy as well in terms of the period of time that they stand Tagrisso.

正如 Susan 所說，雖然我們認為大多數患者將被視為最適合單藥治療，因為它是口服的，因為我們正在接近 2 年 PFS，並且因為對於某些患有疾病的患者來說，副作用情況是眾所周知的看起來更具攻擊性，使用 FLAURA2 獲得該響應率將被視為具有吸引力。我認為，這可能會轉化為治療持續時間以及他們接受 Tagrisso 的時間的進一步增長。

Thank you, Dave. We'll take the last question, Amar Singh with Intron. Go ahead, Amar.

謝謝你，戴夫。我們將回答最後一個問題，Amar Singh 和 Intron。去吧，阿馬爾。

Naresh Chouhan from Intron. Just a question on -- or a couple of questions Calquence, please. Some work we've done suggests that encasing into that CLL space. Just could you help us understand how fast the BTK class is growing. And then secondly, how do you see pricing evolving for the BTK and particularly from Calquence? It seems to us improve pricing fallen quite materially over the last year or so.

來自 Intron 的 Naresh Chouhan。請就 Calquence 提出一個或幾個問題。我們所做的一些工作建議將其封裝到該 CLL 空間中。您能否幫助我們了解 BTK 類的增長速度。其次，您如何看待 BTK，尤其是 Calquence 的定價演變？在我們看來，價格在過去一年左右大幅下降。

Thanks. So thanks for the question. On the first of the questions, and really, I guess I'll focus my answer the U.S. What we're seeing is that Venetoclax has been relatively stable in terms of its frontline second line and, frankly, third-line CLL share. I think that -- within that context, we have actually seen growth in the BTKi class. I think 1 of the benefits that's come from a new entrant in this next-generation BTKi's is that it's created class growth, which I think has been certainly beneficial to Calquence.

謝謝。所以謝謝你的問題。關於第一個問題，實際上，我想我會集中回答美國。我們所看到的是，維奈托克在一線二線和三線 CLL 份額方面一直相對穩定。我認為——在這種情況下，我們實際上已經看到了 BTKi 類的增長。我認為下一代 BTKi 的新加入者帶來的好處之一是它創造了班級增長，我認為這對 Calquence 肯定是有益的。

In terms of your second question, it's a good one and an important one. Historically, I've commented that contracting pricing gross to net has been relatively, I would say, sort of rational and lower pressure, we do see mounting gross to net pressures in the U.S. within the BTKI class. And I do think that as we look forward towards IRA and negotiation and the possibility that first-generation BTIs enter in that, that's something that we certainly expect to see more pressures on the class moving forward.

關於你的第二個問題，這是一個很好的問題，也是一個重要的問題。從歷史上看，我曾評論說，合同定價毛對淨一直是相對的，我會說，有點理性和較低的壓力，我們確實看到美國 BTKI 類別中的毛對淨壓力越來越大。我確實認為，當我們期待 IRA 和談判以及第一代 BTI 參與其中的可能性時，我們當然希望看到班級向前邁進的更多壓力。

Thanks, Dave. So thank you so much for all your great questions, and we wish you a great rest of the day. Thanks. Bye-bye.

謝謝，戴夫。非常感謝您提出的所有重要問題，祝您今天休息愉快。謝謝。再見。