AstraZeneca PLC (AZN) 2024 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 first quarter results 2024 webinar for investors and analysts. Before I hand over to AstraZeneca, I'd like to read the safe harbor statement.

來自英國和美國的人們早安。亞洲聽眾晚上好。女士們、先生們，歡迎參加阿斯特捷利康為投資者和分析師舉辦的 2024 年第一季業績網路研討會。在我移交給阿斯特捷利康之前，我想閱讀安全港聲明。

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.

該公司打算利用 1995 年美國私人證券訴訟改革法案的安全港條款。儘管我們相信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明示或暗示的結果存在重大差異的因素的影響。

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 and webinar. (Operator Instructions)

本次電話會議中所做的任何前瞻性陳述均反映了本次電話會議時可獲得的知識和資訊。該公司不承擔更新前瞻性陳述的義務。請同時仔細閱讀本簡報和網路研討會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'll now hand you over to the company.

現在我就把你交給公司了。

A warm welcome to AstraZeneca's First Quarter 2024 Presentation Conference Call and Webcast. I'm Andy Barnett, Head of Investor Relations at AstraZeneca. And before I hand over to Pascal and other members of the executive team, I would like to cover some important housekeeping points.

熱烈歡迎阿斯特捷利康 2024 年第一季示範電話會議和網路廣播。我是安迪‧巴尼特 (Andy Barnett)，阿斯特捷利康 (AstraZeneca) 投資者關係主管。在我向帕斯卡和執行團隊的其他成員移交之前，我想先介紹一些重要的內務要點。

Firstly, all of the materials presented today are available on our website. This slide contains our safe harbor statement, which I'd encourage you to take the time to read. We will be making comments on our performance using constant exchange rates, or CER, core financial numbers and other non-GAAP measures. A non-GAAP to GAAP reconciliation is contained within the results announcement. All numbers quoted are in millions of U.S. dollars, unless otherwise stated.

首先，今天提供的所有材料都可以在我們的網站上找到。這張投影片包含我們的安全港聲明，我鼓勵您花時間閱讀該聲明。我們將使用固定匯率（CER）、核心財務數據和其他非公認會計準則衡量標準對我們的業績進行評論。績效公告中包含非公認會計原則與公認會計原則的調節。除非另有說明，所有引用的數字均以百萬美元為單位。

This shows the agenda for today's call. And following our prepared remarks, we will open the line for questions. As usual, we will try and address as many questions as we can during the allotted time, although I would ask participants to limit the number of questions you ask to allow others a fair chance participate in the Q&A.

這顯示了今天電話會議的議程。在我們準備好的發言之後，我們將開放提問熱線。像往常一樣，我們將嘗試在規定的時間內回答盡可能多的問題，但我會要求參與者限制提出的問題數量，以便其他人有公平的機會參與問答。

And with that, Pascal, I will hand over to you.

帕斯卡，接下來我就把任務交給你了。

Thank you, Andy. Good day, everybody. I'm pleased to report that we have made a very strong start in 2024.

謝謝你，安迪。大家好。我很高興地報告，我們在 2024 年取得了良好的開局。

Total revenue grew by 19% in the first quarter, reflecting continued strong demand. And core earnings per share rose by 20 -- 13%, sorry. Recall, the first quarter of 2023 benefited from a $240 million gain in other operating income following the divestment of Pulmicort Flexhaler in the U.S. Collaboration revenue and other operating income were minimal this quarter, which makes the EPS year-over-year growth all the more impressive.

第一季總營收成長 19%，反映出持續強勁的需求。抱歉，每股核心收益成長了 20% - 13%。回想一下，2023 年第一季受益於美國 Pulmicort Flexhaler 撤資後其他營業收入增加 2.4 億美元。

We're also pleased to announce an increase in the annual dividend of 7% at the Annual General Meeting earlier this month. This increase is in line with our progressive dividend policy and reflects the continuing strength of AstraZeneca's investment proposition for shareholders.

我們也很高興地在本月稍早的年度股東大會上宣布將年度股息增加 7%。這一增長符合我們的漸進式股利政策，並反映了阿斯特捷利康對股東的投資主張的持續優勢。

Please advance to the next slide. We saw strong double-digit growth across our therapy areas in the first quarter. This is also the first quarter where quarterly revenue from our Oncology and BioPharma businesses exceeded $5 billion and Rare Disease exceeded $2 billion, reflecting the value our medicines bring to patients globally. We saw 19% growth in both the U.S. and Europe this quarter, driven by strong demand. Our business grew substantially in the emerging markets. And growth was especially pronounced outside of China, driven by our sustained presence and commitment to this market.

請前進到下一張幻燈片。第一季我們的治療領域實現了兩位數的強勁成長。這也是我們的腫瘤學和生物製藥業務季度收入首次超過 50 億美元，罕見疾病業務季度收入超過 20 億美元，反映了我們的藥品為全球患者帶來的價值。在強勁需求的推動下，本季美國和歐洲的成長率為 19%。我們的業務在新興市場大幅成長。在我們對這個市場的持續存在和承諾的推動下，中國以外地區的成長尤其明顯。

Next slide, please. Our strong pipeline momentum has continued into 2024. We announced positive trial results for LAURA and ADRIATIC, both of which have been selected presentation during the ASCO plenary, reflecting the important benefits seen for lung cancer patients. As a reminder, there are five presentations at the plenary, so two out of five is a very unusual result.

請下一張投影片。我們強勁的產品線動能將持續到 2024 年。提醒一下，全體會議上有五次發言，所以五分之二是一個非常不尋常的結果。

We saw a number of exciting new approvals in the first quarter. The approval of Tagrisso in combination with chemotherapy establishes a new benchmark for efficacy in frontline EGFR-mutated non-small cell lung cancer. The approval of Enhertu in previously treated HER2-positive cancers is the first tumor-agnostic approval for HER2-directed therapy and offers new hope for patients with the right range of cancers.

第一季我們看到了許多令人興奮的新批准。 Tagrisso 與化療合併用藥的核准為第一線 EGFR 突變非小細胞肺癌的療效樹立了新基準。 Enhertu 已獲準用於先前接受過治療的 HER2 陽性癌症，這是第一個與腫瘤無關的 HER2 標靶治療獲批，為患有適當癌症範圍的患者帶來了新的希望。

And finally, Ultomiris was approved in NMOSD. And we are now working on establishing Ultomiris as the new standard of care for this debilitating disease. This approval is further building on the momentum we are seeing from other recent approval listed here. And we're investing to ensure that each of these new opportunities reach full commercial potential.

最終，Ultomiris 獲得了 NMOSD 的批准。我們現在正在努力將 Ultomiris 作為這種使人衰弱的疾病的新護理標準。此次批准進一步鞏固了我們從此處列出的其他近期批准中看到的勢頭。我們正在進行投資，以確保這些新機會充分發揮商業潛力。

ADRIATIC and LAURA, if approved, coupled with the three approvals I've just described and the ongoing launches, have the potential to deliver several billion dollars in total revenue -- additional revenue in 2030. And this is what our pipeline is delivering in the first quarter of 2024.

ADRIATIC 和LAURA 如果獲得批准，再加上我剛才描述的三個批准和正在進行的發布，有可能帶來數十億美元的總收入——到2030 年的額外收入。的2024 年第一季。

With that, please advance to the next slide. And I will hand over to Aradhana, who will take you through our first quarter financials.

接下來，請前進到下一張投影片。我將把工作交給阿拉達納，他將向您介紹我們第一季的財務狀況。

Thank you, Pascal. And as usual, I will start with our reported P&L. Please turn to the next slide.

謝謝你，帕斯卡。像往常一樣，我將從我們報告的損益表開始。請翻到下一張投影片。

Total revenue in the first quarter increased by 19% to $12.7 billion, predominantly resulting from strong product sales, which grew by 18%. The underlying demand for our medicines across the board was very strong in the quarter across both brands and across geographies. And HER2 and Tezpire continued their strong growth trajectory. And as a result, Alliance revenue increased by 59% to $457 million, driven by profit shares in regions where our partner booked product sales.

第一季總營收成長 19%，達到 127 億美元，主要得益於強勁的產品銷售，成長了 18%。本季度，各個品牌和各個地區對我們藥品的整體潛在需求都非常強勁。 HER2 和 Tezpire 繼續保持強勁的成長軌跡。結果，在我們合作夥伴預訂產品銷售的地區的利潤分成的推動下，Alliance 收入成長了 59%，達到 4.57 億美元。

Please turn to the next slide, which shows our core P&L. The product sales core gross margin was 82% in the quarter. As previously stated, we still expect gross margin for the year to be slightly lower than last year due to strong growth for partner medicines, including in Enhertu and Tezpire, as well as increased product supply to Sanofi for Beyfortus into the 2024/'25 RSV season. In the second half, we see additional impact from usual seasonal impact from medicines such as FluMist.

請翻到下一張投影片，其中顯示了我們的核心損益表。該季度產品銷售核心毛利率為82%。如前所述，由於 Enhertu 和 Tezpire 等合作夥伴藥品的強勁增長，以及 2024/'25 RSV 中對賽諾菲 Beyfortus 的產品供應增加，我們仍預計今年的毛利率將略低於去年季節。下半年，我們看到 FluMist 等藥物通常季節性影響帶來的額外影響。

Total operating expense increased by 15% in the quarter. R&D spend increased by 18%, partly driven by the Phase III trial starts, including our dapa combinations with baxdrostat and balcinerone. We continue to anticipate R&D spend will remain in the low 20s percentage of total revenue, inclusive of investments we are making to maximize the potential medicines acquired in recent business development transactions.

本季總營運費用增加了 15%。研發支出增加了 18%，部分原因是 III 期試驗的啟動，包括我們的 dapa 與 baxdrostat 和 balcinerone 的組合。我們繼續預期研發支出佔總收入的比例將保持在 20% 以下，其中包括我們為最大限度地利用最近業務開發交易中獲得的潛在藥品而進行的投資。

We continue to show operating leverage. Supporting the 19% revenue growth, SG&A increased by 13% in the quarter. We have seen strong initial uptake for Airsupra, Truqap and Wainua in the U.S., and we're investing behind this revenue growth as well as behind our existing brands, such as Breztri and Farxiga.

我們繼續展示營運槓桿。本季 SG&A 成長 13%，支撐了 19% 的營收成長。我們看到 Airsupra、Truqap 和 Wainua 在美國的初期銷售強勁，我們正在投資支持這一收入成長以及我們現有的品牌，例如 Breztri 和 Farxiga。

We're also increasing our promotional efforts behind our Rare Disease medicines to support continued growth. We anticipate quarterly variations in our operating expenses, given the nature of our business. Despite limited contribution from other operating income this quarter, we saw core operating profit growth of 15% and core EPS of $2.06.

我們也加大了罕見疾病藥物的推廣力度，以支持持續成長。鑑於我們業務的性質，我們預計營運費用會出現季度變化。儘管本季其他營業收入的貢獻有限，但我們看到核心營業利潤成長了 15%，核心每股收益為 2.06 美元。

Please turn to the next slide. In the first quarter, cash flow from operations was $2.5 billion. We saw CapEx of $417 million in the quarter. And we continue to anticipate CapEx to increase by approximately 50% on a full year basis to support increased manufacturing capacity and support our growth.

請翻到下一張投影片。第一季營運現金流為 25 億美元。我們看到本季的資本支出為 4.17 億美元。我們繼續預計全年資本支出將成長約 50%，以支持製造能力的提高和我們的成長。

We had deal payments of $2.9 billion, including upfront payments for Icosavax and Gracell acquisition, both of which closed during the first quarter. We also paid the third and final payment to the former shareholders of Acerta. Lastly, we paid the second interim dividend for 2023.

我們的交易付款額為 29 億美元，包括收購 Icosavax 和 Gracell 的預付款，這兩家公司均在第一季完成。我們也向 Acerta 的前股東支付了第三筆也是最後一筆付款。最後，我們支付了2023年第二次中期股利。

At the end of our Q1, our net debt-to-EBITDA ratio was 1.9x. We anticipate the announced Fusion and Amolyt transactions to close in the coming months, strengthening our radiopharmaceutical capabilities and expanding our presence in rare endocrinology. As a result of recent business development and debt refinancing, we expect finance expenses to grow compared to prior year. Reflecting the strength of our business, we are reiterating our full year guidance for both total revenue and core EPS at constant exchange rates.

第一季末，我們的淨負債與 EBITDA 比率為 1.9 倍。我們預計已宣布的 Fusion 和 Amolyt 交易將在未來幾個月內完成，從而增強我們的放射性藥物能力並擴大我們在罕見內分泌學領域的業務。由於近期的業務發展和債務再融資，我們預計財務費用將比去年有所增長。為了反映我們業務的實力，我們重申了以固定匯率計算的總收入和核心每股盈餘的全年指引。

With that, please advance to the next slide. And I will hand over to Dave, who will take you through our Oncology performance.

接下來，請前進到下一張投影片。我將把時間交給戴夫，他將帶您觀看我們的腫瘤學表演。

Thank you, Aradhana. Next slide, please. Oncology total revenues grew 26% to $5.1 billion in the first quarter, driven both by double-digit growth across all regions and strong demand for our key medicines. Tagrisso global revenues grew 15% in the quarter, reflecting continued global demand for ADAURA and FLAURA. Following U.S. approval in February, we've seen strong interest and early uptake for FLAURA2 in the frontline setting, with oncologists particularly focused on patients with L858R mutations and CNS metastases at baseline.

謝謝你，阿拉達納。請下一張投影片。第一季腫瘤學總收入成長 26%，達到 51 億美元，這得益於所有地區兩位數的成長以及對我們關鍵藥物的強勁需求。 Tagrisso 本季全球營收成長 15%，反映出全球對 ADAURA 和 FLAURA 的持續需求。繼 2 月在美國獲得批准後，我們在一線環境中看到了對 FLAURA2 的強烈興趣和早期採用，腫瘤學家特別關注在基線時存在 L858R 突變和 CNS 轉移的患者。

Lynparza delivered product sales growth of 11% in the first quarter and remains the leading PARP inhibitor globally across all tumor types. Imfinzi total revenues grew 33% on continued strength in biliary tract cancer with TOPAZ-1, which is now approaching peak market share penetration in the U.S., Japan and Europe. Launches continue at pace across emerging markets, where biliary tract incidence and prevalence is high. And as previously communicated, we recognized a 25% mandatory price reduction in Japan effective from February 1 and anticipate a second mandatory price discount later this year.

Lynparza 第一季的產品銷售成長了 11%，在所有腫瘤類型中仍然是全球領先的 PARP 抑制劑。由於 TOPAZ-1 在膽道癌領域的持續強勁表現，Imfinzi 的總收入增長了 33%，該藥物目前在美國、日本和歐洲的市場份額滲透率已接近峰值。在膽道發病率和患病率較高的新興市場，產品繼續快速上市。正如之前所傳達的，我們認識到日本將從 2 月 1 日起強制降價 25%，並預計今年稍後將進行第二次強制降價。

For the first time, we have split out Imjudo in our reporting and are please with its launch trajectory. We've established a strong foundation in hepatocellular carcinoma with HIMALAYA and see continued growth in non-small cell lung cancer with POSEIDON. Calquence total revenues increased 35% in the first quarter, driven by sustained BTK inhibitor leadership in frontline CLL across the U.S. and Europe.

我們第一次在報告中單獨列出了 Imjudo，並對它的發布軌跡感到滿意。我們已經透過 HIMALAYA 為肝細胞癌奠定了堅實的基礎，並且透過 POSEIDON 看到了非小細胞肺癌的持續增長。在 BTK 抑制劑在美國和歐洲一線 CLL 領域持續領先的推動下，Calquence 第一季度總收入成長了 35%。

Enhertu total revenues increased 79% in the first quarter. Again, we drove sequential market share growth in second-line HER2-positive breast cancer in the U.S. and Europe, where considerable growth remains. We see continued adoption in HER2-low across many global markets and eagerly await the DESTINY-Breast06 readout, which brings the potential for further expansion, moving Enhertu one line earlier.

Enhertu 第一季總營收成長 79%。我們再次推動了美國和歐洲二線 HER2 陽性乳癌的市場份額連續成長，這些市場仍然保持著可觀的成長。我們看到 HER2-low 在許多全球市場上持續採用，並熱切地等待 DESTINY-Breast06 讀數，這帶來了進一步擴展的潛力，使 Enhertu 提前了一行。

Following approval in November last year, we are pleased with the strong Truqap adoption in the biomarker-altered population, achieving $50 million in the first quarter total revenues. Looking forward, we anticipate further expansion of Tagrisso with the approval of FLAURA2 in frontline non-small cell lung cancer and maximizing the U.S. launch of Enhertu across HER2-expressing tumors.

繼去年 11 月獲得批准後，我們對 Truqap 在生物標誌物改變人群中的強勁採用感到高興，第一季總收入達到 5000 萬美元。展望未來，我們預計隨著 FLAURA2 在一線非小細胞肺癌中的批准，Tagrisso 將進一步擴展，並最大限度地在美國推出針對 HER2 表達腫瘤的 Enhertu。

Lastly, we're excited that both ADRIATIC in limited stage and LAURA in stage 3 unresectable lung cancer have been selected for the ASCO plenary session. Each of these represents substantial growth opportunities in the near future and beyond, as Pascal has already outlined.

最後，我們很高興看到有限期間的 ADRIATIC 和 3 期不可切除肺癌的 LAURA 都被選為 ASCO 全體會議的成員。正如帕斯卡已經概述的那樣，每一個都代表著在不久的將來及以後的巨大增長機會。

With that, please advance to the next slide. And I'll hand over to Susan to cover key R&D highlights in the quarter.

接下來，請前進到下一張投影片。我將由 Susan 介紹本季的主要研發亮點。

Thank you, Dave. We've had an exciting start to the year with a number of key presentations, including data for our new-generation PARP inhibitor, saruparib, in advanced solid tumors presented at this year's AACR.

謝謝你，戴夫。今年的開局令人興奮，我們做了許多重要的演講，包括今年的 AACR 上展示的新一代 PARP 抑制劑 saruparib 在晚期實體瘤中的數據。

This quarter, we announced the proposed acquisition of Fusion Pharmaceuticals, furthering our ambition to redefine the backbone of current cancer treatment. Along with chemotherapy, radiotherapy has been a mainstay of cancer treatment for decades. In fact, 30% to 50% of all patients receive radiotherapy. And whilst this treatment is effective, there's also toxic off-target effects.

本季度，我們宣布擬收購 Fusion Pharmaceuticals，進一步堅定了我們重新定義目前癌症治療支柱的野心。幾十年來，與化療一樣，放療一直是癌症治療的主要手段。事實上，30% 到 50% 的患者接受了放射治療。雖然這種治療有效，但也存在有毒的脫靶效應。

Fusion has developed a clinical-stage portfolio of radioconjugates that are designed to deliver radiation therapy to tumor cells in a more targeted manner than external beam radiation. As we've discussed already, we believe the future of cancer care is in combinations. And there's immense potential to combine radioconjugates with other modalities in our pipeline, including next-generation IO bispecifics, cell therapy, T-cell engagers and our DNA damage response agents.

Fusion 開發了臨床階段的放射性結合物組合，旨在以比外部束輻射更有針對性的方式對腫瘤細胞進行放射治療。正如我們已經討論過的，我們相信癌症治療的未來在於組合。將放射性結合物與我們管道中的其他方式結合起來具有巨大的潛力，包括下一代 IO 雙特異性藥物、細胞療法、T 細胞接合劑和我們的 DNA 損傷反應劑。

Importantly, the planned acquisition of Fusion accelerates our radiopharmaceutical manufacturing to commercial-scale capabilities by over 3 years and offers additional security in actinium supply with multi-source supply agreements in place.

重要的是，計劃收購 Fusion 將使我們的放射性藥物製造加速到商業規模能力超過 3 年，並透過多源供應協議提供額外的錒供應保障。

The lead pipeline candidate, FPI-2265, has potential to be the first actinium-based PSMA-targeted radiotherapy approved for the treatment of post-lutetium metastatic castrate-resistant prostate cancer. FPI-2265 is differentiated and has potential to be both more potent and tolerable than currently approved beta emitter radioconjugates.

主要候選產品 FPI-2265 有可能成為第一個被批准用於治療镥後轉移性去勢抵抗性前列腺癌的錒基 PSMA 標靶放射療法。 FPI-2265 是與眾不同的，並且有可能比目前批准的 β 發射體放射性結合物更有效、更耐受。

Data presented earlier this month at AACR demonstrated further validation of FPI-2265's efficacy and tolerability. PSA50 response was achieved in 50% of patients overall and 43% of the lutetium-treated patient population and 54% of the lutetium-naive population. Furthermore, there were 0 discontinuations related to xerostomia, a common toxicity. We believe that our proven expertise in targeted delivery, together with Fusion's clinical-stage portfolio and manufacturing capabilities, presents an opportunity for clear leadership in the radioconjugate space.

本月稍早在 AACR 上公佈的數據進一步驗證了 FPI-2265 的功效和耐受性。總體而言，50% 的患者、43% 的镥治療患者群體和 54% 的未接受镥治療的患者群體實現了 PSA50 緩解。此外，與口乾症（一種常見的毒性）相關的停藥次數為 0 次。我們相信，我們在標靶遞送方面經過驗證的專業知識，加上 Fusion 的臨床階段產品組合和製造能力，為在放射性共軛領域取得明確的領導地位提供了機會。

And with that, please advance to the next slide. And I'll pass over to Ruud to cover BioPharmaceuticals' performance.

接下來，請前進到下一張投影片。我將由 Ruud 來報道生物製藥公司的表現。

Thank you, Susan. Next slide, please. BioPharmaceuticals delivered total revenue of $5.2 billion in the first quarter of 2024, representing growth of 16%. Our key underlying growth drivers remain in place, including the continued growth of the largest cardiorenal medicine on the market, Farxiga, the increased uptake of medicines in severe asthma and the ongoing momentum behind Breztri, our inhaled COPD medicine.

謝謝你，蘇珊。請下一張投影片。生物製藥業務 2024 年第一季總營收達 52 億美元，成長 16%。我們的主要潛在成長動力仍然存在，包括市場上最大的心腎藥物 Farxiga 的持續成長、嚴重氣喘藥物使用量的增加以及我們的吸入性慢性阻塞性肺病藥物 Breztri 的持續成長勢頭。

In the United States, demand for Farxiga were strong in the quarter and benefited from the launch of an authorized generic. We saw solid growth in emerging markets despite entry of generic competition in some countries. Presently, we still anticipate Farxiga may be included in China VBP in the second half of 2024.

在美國，本季對 Farxiga 的需求強勁，並受益於授權仿製藥的推出。儘管一些國家出現了仿製藥競爭，但我們仍看到新興市場的穩健成長。目前，我們仍預期 Farxiga 可能會在 2024 年下半年被納入中國 VBP。

Additionally, we saw a strong Symbicort performance in the first quarter despite generic pressures. This was particularly evident in emerging markets, where we saw strong underlying demand in both China and ex China markets, strengthening its position as market leader in the region.

此外，儘管面臨普遍壓力，我們在第一季仍看到了 Symbicort 的強勁表​​現。這在新興市場尤其明顯，我們看到中國和中國以外市場的強勁潛在需求，鞏固了在該地區市場領導者的地位。

Awareness of Airsupra continues to grow. And more than 18,000 health care practitioners have prescribed this new medicine, translating into 65,000 prescriptions in the quarter. The performance has been particularly strong among specialists. Airsupra already has over 15% of new share prescriptions by allergists and over 10% share of prescriptions from pulmonologists.

Airsupra 的知名度不斷提高。超過 18,000 名醫療保健從業人員開出了這種新藥，本季開出了 65,000 張處方。專家們的表現尤其強勁。 Airsupra 已經擁有超過 15% 的新處方份額來自過敏科醫生，超過 10% 的處方份額來自肺科醫師。

As Airsupra is still in the first few months of launch, our revenues in quarter 1 did not reflect the full extent of initial demand due to introductory discounts. These introductory discounts will fade through the year as we continue to expand access.

由於 Airsupra 仍處於推出的前幾個月，由於介紹性折扣，我們第一季的營收並未完全反映初始需求。隨著我們繼續擴大訪問範圍，這些介紹性折扣將在一年中逐漸消失。

Awareness is also building for Wainua. And we are very pleased to report our first revenues this quarter, following its recent approval for ATTR polyneuropathy in the United States. Wainua has only been available for a few weeks. But we are seeing good uptake among patients, including some who are new to the class of medicine and some that have switched from other brands.

懷努阿的意識也在增強。繼最近在美國批准 ATTR 多發性神經病變治療後，我們非常高興地報告本季的第一份收入。懷努阿 (Wainua) 僅開放幾週時間。但我們看到患者的使用情況良好，其中包括一些剛接觸該類藥物的患者和一些從其他品牌轉用該藥物的患者。

Finally, we saw continued sales from Beyfortus in quarter 1, albeit with the expected seasonal drop versus quarter 4. We were particularly pleased to see the real-world data coming out of the U.S. with the Center for Disease Control reporting that Beyfortus was 90% effective at preventing infants from being hospitalized with RSV.

最後，我們看到Beyfortus 在第一季的銷售持續成長，儘管預計與第四季度相比會出現季節性下降。率為90%有效預防嬰兒因 RSV 住院。

Next slide, please. I will now hand over to Sharon to discuss our ongoing development program for Wainua in TTR cardiomyopathy, where we have the potential to reach up to 0.5 million patients globally.

請下一張投影片。我現在將請 Sharon 討論我們正在進行的針對 TTR 心肌病變的 Wainua 開發計劃，我們有潛力覆蓋全球多達 50 萬名患者。

Thanks, Ruud. I wanted to take the opportunity to highlight results from a 66-week analysis of exploratory cardiac endpoints in the Phase III NEURO-TTRansform study of Wainua in hereditary ATTR polyneuropathy.

謝謝，路德。我想藉此機會重點介紹 Wainua 遺傳性 ATTR 多發性神經病變 III 期 NEURO-TTRansform 研究中對探索性心臟終點進行的 66 週分析的結果。

In a predefined cardiac subgroup of hereditary ATTR polyneuropathy patients, treatment with eplontersen showed stabilization or improvement in cardiac function and structure relative to external placebo, including levels of NT-proBNP, a measure of cardiac stress, and a trend towards improvement in echocardiographic parameters such as left ventricular wall thickness, diastolic and stroke volume.

在遺傳性ATTR 多發性神經病變患者的預定義心臟亞群中，與外部安慰劑相比，eplontersen 治療顯示心臟功能和結構穩定或改善，包括NT-proBNP 水平（心臟壓力指標）以及超音波心動圖參數改善的趨勢，例如如左心室壁厚度、舒張壓和每搏輸出量。

These results provide confidence in our Phase III CARDIO-TTRansform trial in ATTR cardiomyopathy. ATTR cardiomyopathy is a systemic, progressive and fatal condition that typically leads to progressive heart failure and often death within 3 to 5 years from disease onset. With more than 1,400 patients enrolled, CARDIO-TTRansform is the largest, most comprehensive ATTR cardiomyopathy study and importantly includes cardiovascular outcome endpoints.

這些結果為我們針對 ATTR 心肌病變的 III 期 CARDIO-TTRansform 試驗提供了信​​心。 ATTR 心肌病變是一種系統性、進行性和致命性疾病，通常會導致進行性心臟衰竭，並常在發病後 3 至 5 年內死亡。 CARDIO-TTRansform 招募了 1,400 多名患者，是規模最大、最全面的 ATTR 心肌病變研究，重要的是包括心血管結局終點。

In other key programs, we continue to maximize the opportunity for our best-in-class SGLT2 inhibitor, Farxiga. We have the potential to manage cardiorenal disease through three distinct mechanisms, complementary dual mechanisms combining dapagliflozin with balcinerone, baxdrostat or zibotentan. I am delighted to announce that all three combinations are now in Phase III.

在其他關鍵項目中，我們繼續最大限度地利用我們一流的 SGLT2 抑制劑 Farxiga 的機會。我們有潛力透過三種不同的機制來治療心腎疾病，即達格列淨與巴西奈隆、baxdrostat 或 zibotentan 相結合的互補雙重機制。我很高興地宣布，所有三種組合現已進入第三階段。

Please move to the next slide, and I will now hand over to Marc, who will cover our Rare Disease portfolio.

請移至下一張投影片，我現在將工作交給 Marc，他將負責我們的罕見疾病組合。

Thank you, Sharon. Can I get the next slide, please? I'm delighted to report Rare Disease delivered our first $2 billion total revenue quarter, up 16% year-on-year. The growth rate that's here includes a small benefit from countries with high inflation. Growth was driven by neurology indication, increased patient demand and launches in new markets.

謝謝你，莎倫。我可以拿下一張投影片嗎？我很高興地報告罕見疾病第一個季度總收入達到 20 億美元，年增 16%。這裡的成長率包括高通膨國家帶來的一小部分好處。成長的推動因素包括神經病學適應症、患者需求的增加以及新市場的推出。

In the quarter, Ultomiris revenue grew 34% with the vast majority of growth coming from generalized myasthenia gravis. gMG patients grew by 41%, driven by demand in Europe and established rest of the world. In the U.S., we saw the highest number of new-to-brand patients in the quarter, supported by our increased promotional activities.

本季度，Ultomiris 營收成長了 34%，其中絕大多數成長來自全身性重症肌無力。在歐洲和世界其他地區需求的推動下，gMG 患者成長了 41%。在美國，在我們增加的促銷活動的支持下，本季新品牌患者數量最多。

During the quarter, we received U.S. approval of Ultomiris in NMOSD. In the Phase III CHAMPION-NMOSD trial, Ultomiris demonstrated 0 adjudicated relapses over 138 weeks. Given the strength of this data, we expect Ultomiris to be the treatment of choice for relapsing patients naive to biologics. We expect patient on Soliris convert to Ultomiris over the short term.

本季度，我們在 NMOSD 中獲得了美國對 Ultomiris 的批准。在 III 期 CHAMPION-NMOSD 試驗中，Ultomiris 在 138 週內證明零復發。鑑於這些數據的強度，我們預計 Ultomiris 將成為未接受過生物製劑的複發患者的首選治療方法。我們預期接受 Soliris 治療的患者會在短期內轉為 Ultomiris。

Following approval in U.S. and the EU of Voydeya, an add-on therapy, ensure that PNH patients who experience clinically significant extravascular hemolysis are able to continue on standard of care, Ultomiris or Soliris. Beyond complement, both Strensiq and Koselugo grew 21% and 80%, respectively, driven by continued patient demand as well as order timing in certain tender markets.

附加療法 Voydeya 在美國和歐盟獲得批准後，可確保經歷臨床顯著血管外溶血的 PNH 患者能夠繼續接受標準護理、Ultomiris 或 Soliris。除了補充之外，在持續的患者需求以及某些招標市場的訂單時機的推動下，Strensiq 和 Koselugo 分別成長了 21% 和 80%。

Please advance to the next slide. During the quarter, we announced our plans to acquire Amolyt Pharma, which includes a Phase III asset, eneboparatide, for patients with hypoparathyroidism. Hypoparathyroidism is characterized by deficiency in parathyroid hormone production, which results in significant disregulation of calcium and phosphate leading to life-altering symptoms and complications, potentially including chronic kidney disease. It is one of the largest known rare diseases.

請前進到下一張幻燈片。在本季度，我們宣布了收購 Amolyt Pharma 的計劃，其中包括針對副甲狀腺功能減退症患者的 III 期資產 enboparatide。副甲狀腺功能減退症的特徵是副甲狀腺素生成不足，導致鈣和磷酸鹽的嚴重失調，進而導致改變生活的症狀和併發症，可能包括慢性腎臟病。它是已知最大的罕見疾病之一。

Phase IIa data from eneboparatide showed a normalization of serum calcium level and a reduction in dependence on daily calcium and vitamin D supplements, both clinical priorities for treating patients. Data also suggested that eneboparatide has a potential to restore normal bone turnover and preserve bone mineral density. We believe eneboparatide has blockbuster potential and anticipate data from the Phase III CALYPSO trial in 2025.

eneboparatide 的 IIa 期數據顯示，血清鈣水平正常化，並且減少了對每日鈣和維生素 D 補充劑的依賴，這都是治療患者的臨床優先事項。數據還表明，依波帕肽有可能恢復正常的骨轉換並保持骨礦物質密度。我們相信 enboparatide 具有重磅炸彈的潛力，並預計 2025 年 III 期 CALYPSO 試驗的數據。

With that, please advance to the next slide. And I will hand back to Pascal for closing remarks.

接下來，請前進到下一張投影片。我將請帕斯卡作結束語。

Thank you, Marc. Can I have the next slide, please? As you have heard, our company has made a very strong start to 2024 with demand for our medicines continuing to grow. Looking ahead, we are once again anticipating multiple pivotal trials to read throughout the remainder of the year. Several important potential catalysts are shown here, as well as DESTINY-Breast06, which Dave spoke about earlier, I would like to highlight CAPItello-281, which will be the first registrational study of Truqap in prostate cancer, an important potential new growth driver for this medicine.

謝謝你，馬克。我可以看下一張投影片嗎？如您所知，我們公司在 2024 年取得了良好的開局，對我們藥品的需求持續成長。展望未來，我們再次期待在今年剩餘時間內進行多項關鍵試驗。這裡展示了幾個重要的潛在催化劑，以及Dave 之前談到的DESTINY-Breast06，我想強調CAPtello-281，這將是Truqap 在前列腺癌中的第一個註冊研究，前列腺癌是一個重要的潛在新增長動力這個藥。

Since our full year 2023 update, we have initiated the eight pivotal trials shown here, all of which are potentially transformative for patients and could meaningfully accelerate our growth. In addition to the exceptional delivery from our internal pipeline, we've also been very active with business development, building capabilities and adding new platforms to strengthen our R&D efforts in key areas which we believe have the potential to radically improve patient outcomes, including radioconjugates, gene therapies and cell therapies.

自 2023 年全年更新以來，我們已經啟動了此處顯示的八項關鍵試驗，所有這些試驗都對患者俱有潛在的變革性，並且可以有意義地加速我們的成長。除了我們內部管道的出色交付外，我們還非常積極地進行業務開發、能力建設和增加新平台，以加強我們在關鍵領域的研發工作，我們相信這些領域有可能從根本上改善患者的治療效果，包括放射性共軛物、基因療法和細胞療法。

We're very much looking forward to sharing more details about our pipeline and the long-term outlook for our company at our upcoming Investor Day on the 21st of May. Please advance to the next slide, and we will go to the Q&A.

我們非常期待在 5 月 21 日即將舉行的投資者日上分享有關我們的產品線和公司長期前景的更多細節。請前進到下一張投影片，我們將進入問答環節。

(Operator Instructions) And with that, let's move to the first question, which is from James Gordon of JPM.

（操作員說明）接下來，讓我們討論第一個問題，該問題由摩根大通 (JPM) 的詹姆斯·戈登 (James Gordon) 提出。

James Gordon, JPMorgan. First question is on '24 guidance. So it's a very strong revenue growth, 19%. In order not to grow revenues at teens for the year, it looks like you'd need to only grow at about 10% for the rest of the year. So in terms of headwinds, we should be mindful that, that would drive 9 percentage points of deceleration.

詹姆斯‧戈登，摩根大通。第一個問題是關於 '24 指南的。所以這是一個非常強勁的收入成長，達到 19%。為了不讓青少年的收入在這一年增長，看起來你只需要在今年剩餘的時間裡成長 10% 左右。因此，就不利因素而言，我們應該注意，這將導致 9 個百分點的減速。

And then I heard a comment on maybe for Farxiga VBP and Imfinzi price in Japan. But anything else? And in particular, for Farxiga, Symbicort and Tagrisso that were very strong this quarter, are there things through year that we need to watch out for? Or does that look quite sustainable?

然後我聽到了關於 Farxiga VBP 和 Imfinzi 在日本價格的評論。但還有別的嗎？特別是對於本季非常強勁的 Farxiga、Symbicort 和 Tagrisso 來說，全年有哪些事情需要我們注意？或者這看起來相當可持續嗎？

And also on '24 guidance, just on OpEx, the ratios looked pretty good to say. But this is with the strong top line before the two deals closed. So if revenue growth is a little slower through the year and you consolidate these deals, do we need to be careful on those ratios? Or can you still keep a pretty high margin?

而且在 24 年指導中，僅就營運支出而言，比率看起來相當不錯。但這是在兩筆交易結束之前強勁的營收。因此，如果全年收入成長稍慢，並且您合併這些交易，我們是否需要謹慎對待這些比率？或者你還能維持相當高的利潤嗎？

And if I could squeeze in a quick second question, just Eccogene and the oral GLP-1. So I believe you've expanded the trial and maybe taking dosing higher. So on that, what is the latest thinking in terms of when we might see the data? I didn't see a reference to ADA. And how are you now thinking about how competitive this product might look in terms of the weight loss and other aspects versus some other recent readouts from competitors?

我能否快速插話問第二個問題，即 Eccogene 和口服 GLP-1。所以我相信你已經擴大了試驗範圍，並且可能提高了劑量。那麼，關於我們何時可以看到數據的最新想法是什麼？我沒有看到對 ADA 的提及。現在您如何看待該產品在減肥和其他方面與競爭對手最近發布的其他一些產品相比的競爭力？

Thank you, James. Aradhana, maybe you can take the first one. And Sharon, will you take the second one?

謝謝你，詹姆斯。 Aradhana，也許你可以選擇第一個。莎倫，你願意選第二個嗎？

Great. Thank you, James, for the question. It is obviously early in the year. And as you know, generally, we don't update or provide more color on the guidance in the first quarter. You've seen from the reported results, the underlying trend in our revenue product sales is very, very strong across the board. You've also mentioned some of the uncertainties that Ruud also mentioned as well as Dave. So those uncertainties are there for the remainder of the year.

偉大的。謝謝詹姆斯提出的問題。顯然現在是年初。如您所知，一般來說，我們不會在第一季的指導中更新或提供更多資訊。您從報告的結果中看到，我們的收入產品銷售的基本趨勢非常非常強勁。你也提到了路德和戴夫也提到的一些不確定性。因此，這些不確定性在今年剩餘時間內仍然存在。

However, if our momentum continues the way it has been in the first quarter and some of these uncertainties on VBP, pricing, et cetera, are in our favor, you can think about our product revenues, our product sales and Alliance revenues could be at the upper end of our range or higher. But again, we're not updating our guidance at this point.

然而，如果我們的勢頭繼續保持第一季的勢頭，並且 VBP、定價等方面的一些不確定性對我們有利，您可以考慮我們的產品收入、我們的產品銷售和聯盟收入可能會達到我們範圍的上限或更高。但同樣，我們目前不會更新我們的指南。

We will continue to invest in our R&D for the long term, including the acquired product and continue to invest in SG&A to drive the top line momentum that you've seen. Operating leverage continues to be a focus for us. Again, you've seen this quarter as well, 19% revenue growth and 13% SG&A growth. And we will try to maintain stronger revenue growth than expense growth in the coming quarters as well. With that, maybe Sharon?

我們將繼續長期投資於我們的研發，包括收購的產品，並繼續投資於SG&A，以推動您所看到的營收成長動能。營運槓桿仍然是我們關注的焦點。同樣，本季您也看到了 19% 的營收成長和 13% 的 SG&A 成長。我們也將努力在未來幾季維持比支出成長更強勁的營收成長。有了這個，也許莎倫？

Sure. So thank you for the question about AZD5004, our oral GLP-1 receptor agonist. We're really excited about this molecule and its potential to treat the interrelatedness of cardiometabolic and cardiorenal disease. You asked specifically about the Phase I study. And as I'm sure you're aware, we completed, together with Eccogene, a highly controlled inpatient Phase I earlier this year. We have the data in hand and look forward to presenting that at an upcoming medical conference later this year.

當然。感謝您提出有關我們的口服 GLP-1 受體激動劑 AZD5004 的問題。我們對這種分子及其治療心臟代謝和心臟腎臟疾病相互關聯的潛力感到非常興奮。您具體詢問了第一階段研究的情況。我相信您也知道，今年早些時候，我們與 Eccogene 一起完成了高度控制的住院 I 期臨床試驗。我們手頭上有數據，並期待在今年稍後即將召開的醫學會議上展示這些數據。

You also asked about how we view the competitive position of this molecule. And recognizing that it is a highly competitive field, we do feel very optimistic about the potential for this molecule as a standalone as well as in combination. So when we think about how we're treating obesity and metabolic health, I think we honestly do ourselves a disservice by referring to this as obesity. What I'd like us to do is think about this more clearly is treating the interconnectedness of disease.

您也詢問我們如何看待該分子的競爭地位。我們意識到這是一個競爭激烈的領域，我們確實對該分子作為獨立分子和組合分子的潛力感到非常樂觀。因此，當我們思考如何治療肥胖和代謝健康時，我認為我們稱之為肥胖，老實說是對自己造成了傷害。我希望我們更清楚地思考這個問題，即治療疾病的相互關聯性。

And to that end, we are uniquely well positioned to combine this orally available molecule with other molecules in our portfolio that help address those interrelated diseases, as an example, combining 5004 with our SGLT2 inhibitor. So when we think about this, we can imagine that at a fixed dose, we may want one dose that would be compatible for fixed-dose combinations and another dose that would be more compatible for additional weight loss in obesity indications.

為此，我們擁有獨特的優勢，可以將這種口服分子與我們產品組合中的其他分子結合起來，幫助解決這些相關疾病，例如，將 5004 與我們的 SGLT2 抑制劑結合。因此，當我們考慮這一點時，我們可以想像，在固定劑量下，我們可能需要一種適合固定劑量組合的劑量，另一種更適合肥胖適應症的額外體重減輕的劑量。

And we'll keep that in mind as we continue to design our clinical development program. Moving forward, we have publicly stated that we will be launching two Phase IIb studies later this year, one in obesity and one in type 2 diabetes.

當我們繼續設計我們的臨床開發計劃時，我們將牢記這一點。展望未來，我們公開表示，我們將在今年稍後啟動兩項 IIb 期研究，一項針對肥胖症，一項針對 2 型糖尿病。

Thank you, Sharon. And James, you asked the question of the dose, but you've got to remember that not everybody needs to lose the same amount of weight. And so as you target higher weight losses Sharon was talking about in the obesity segment, you would expect to have to go through a titration regimen and get to a higher dose. So it's not surprising that we would explore the doses depending on how much weight loss patients are needing.

謝謝你，莎倫。詹姆斯，你問了劑量的問題，但你必須記住，並不是每個人都需要減掉相同的體重。因此，當您以莎倫在肥胖部分談到的更高的減肥目標時，您會期望必須進行滴定方案並獲得更高的劑量。因此，我們根據患者所需的減重量來探索劑量也就不足為奇了。

The next question is Seamus Fernandez of Guggenheim.

下一個問題是古根漢的謝默斯·費爾南德斯。

Great. So I guess as, Pascal, a little bit of a preview of the upcoming analyst event, just hoping that you could provide us with a little bit of color on how you're thinking about potential for updated guidance. Is the most important factor of the meeting really giving and helping us understand long-term visibility around revenue? Or is it more on margins or a little bit of both?

偉大的。因此，帕斯卡，我想對即將舉行的分析師活動進行一些預覽，只是希望您能為我們提供一些關於您如何考慮更新指導的潛力的信息。會議最重要的因素是否真的能夠幫助我們了解收入的長期可見度？還是更多處於邊緣狀態，或者兩者兼而有之？

And then just a second question, as we think about the three products that you've highlighted on the BioPharma side of the business, the oral PCSK9, the GLP-1 and the long-acting amylin, just hoping you could help us or help provide some context around of the three, which you're most excited about and perhaps when we might see data on all three?

然後是第二個問題，當我們考慮您在生物製藥業務方面強調的三種產品時，口服 PCSK9、GLP-1 和長效胰淀素，只是希望您能幫助我們或幫助提供一些關於這三個方面的背景訊息，您最感興趣的是哪一個，也許我們什麼時候可以看到這三個方面的數據？

Thanks, Seamus. So the first question about the Investor Day, I guess, I would like to invite you to join us in beautiful Cambridge to see more of the details of what we're going to present. But the short answer to your question is a little bit of both. Essentially, what we want to do is show people how we are looking at, what I call, today, tomorrow and the day after.

謝謝，西莫。關於投資者日的第一個問題，我想，我想邀請您來到美麗的劍橋，看看我們將要展示的更多細節。但對你的問題的簡短回答是兩者兼而有之。從本質上講，我們想做的是向人們展示我們如何看待今天、明天和後天，我稱之為什麼。

Today is what do we intend to deliver in terms of our financial progression in '24, '25, '26. Tomorrow is what are the products we are going to launch that will drive our growth between 2025 and 2030 and what is our strategy there, what do we intend to do with our pipeline and what other products we believe are growth drivers to 2030.

今天是我們打算在 24 年、25 年、26 年實現財務進展的目標。明天我們將要推出哪些產品來推動 2025 年至 2030 年的成長，我們的策略是什麼，我們打算如何利用我們的產品線，以及我們認為哪些其他產品是 2030 年的成長動力。

And the day after tomorrow is really the sort of post-2030 period and what do we believe are the technologies that will shape the future of medicine in oncology and beyond and how are we building some of those platforms that will help us shape -- participate in shaping the future of medicine in the therapy areas where we are. So that's really what we want to do at the Investor Day. And we also offer, for those of you who are early risers and will be physically on site, we'll also give you a chance to look around our site and experience a little bit what we have on site.

後天實際上是 2030 年後的時期，我們相信哪些技術將塑造腫瘤學及其他領域的醫學未來，以及我們如何建立一些平台來幫助我們塑造——參與塑造我們所在治療領域的醫學未來。這就是我們在投資者日想要做的事情。我們也為那些早起並親自到現場的人提供機會，讓您有機會參觀我們的網站並體驗我們的現場內容。

The second question, let me give you a couple of comments and then maybe Ruud and Sharon could add. We are always more excited about products for which we have more advanced data. Those three products are, of course, exciting. But we have more data for the PCSK9, which is a very exciting product, and also more data for the oral GLP-1. Long-acting amylin is technically interesting, but we need more data. But it certainly so far looks pretty good.

第二個問題，讓我給你一些評論，然後也許范尼和莎倫可以補充。我們總是對擁有更先進數據的產品感到更加興奮。這三款產品當然令人興奮。但我們有更多關於 PCSK9 的數據，這是一個非常令人興奮的產品，還有更多關於口服 GLP-1 的數據。長效胰淀素在技術上很有趣，但我們需要更多數據。但到目前為止看起來確實不錯。

And we think we can actually, as Sharon said, with the combination of the GLP-1 and the rest of our pipeline, not only PCSK9 but also dapa and also potentially baxdrostat, we can make a difference in this segment of patients who need to lose weight but also manage their cardiovascular risk factors. And in the obese segment, where people need to lose 20%, 25% of their weight, then we can look at combining our overall GLP-1 with the long-acting amylin and some other mechanisms. Sharon, if you want to maybe also add a little bit on how you see this pipeline.

我們認為，正如 Sharon 所說，透過將 GLP-1 和我們的其他產品組合（不僅是 PCSK9，還有 dapa 和潛在的 baxdrostat），我們可以為這部分需要治療的患者帶來改變。要控制心血管危險因子。在肥胖族群中，人們需要減輕 20%、25% 的體重，那麼我們可以考慮將我們的整體 GLP-1 與長效型胰淀素和其他一些機制結合起來。莎倫，如果您願意的話，也許還可以補充一點您如何看待這個管道。

Sure. So I'll jump in on both. People often ask about which molecule I'm more excited about. And I find that very difficult to answer because, obviously, I'm very invested in all of them. But the first one that you asked about was our oral PCSK9 inhibitor. And we are extremely excited about the potential for this molecule. We will be releasing Phase I data at an upcoming conference in the very near future. But I think it's safe to say that we set ourselves a very high bar with this molecule that we asked that it be able to meet a major unmet medical need.

當然。所以我會同時參與這兩方面。人們經常問我對哪種分子比較感興趣。我發現這個問題很難回答，因為顯然我對所有這些都非常投入。但您問到的第一個問題是我們的口服 PCSK9 抑制劑。我們對這種分子的潛力感到非常興奮。我們將在不久的將來召開的會議上發布第一階段數據。但我認為可以肯定地說，我們為這種分子設定了非常高的標準，我們要求它能夠滿足主要的未滿足的醫療需求。

We know that despite high-intensity statins, about half the patients with cardiovascular disease are not hitting their LDL targets. And so we asked this molecule to be able to offer substantial lowering on top of statins. And we're very encouraged by the data that we see. So we are actively moving forward with this molecule in clinical development and thrilled to be sharing the data at an upcoming conference.

我們知道，儘管使用高強度他汀類藥物，但大約一半的心血管疾病患者並未達到低密度脂蛋白目標。因此，我們要求這種分子能夠在他汀類藥物的基礎上提供顯著的降低效果。我們看到的數據讓我們深受鼓舞。因此，我們正在積極推進該分子的臨床開發，並很高興在即將舉行的會議上分享數據。

Relatedly, you asked about our obesity portfolio. And again, I think I would really think of it more as our optimal weight management portfolio, in which we are exploring both incretin and non-incretin pathways as multiple mechanisms to manage both weight and interrelated cardiometabolic and cardiorenal disease. So we are positioned to go beyond short-term weight loss and to deliver long-term weight management and healthy lean mass management, addressing cardiometabolic risk and also organ protection.

與此相關的是，您詢問了我們的肥胖產品組合。再說一遍，我想我真的會更多地將其視為我們的最佳體重管理組合，其中我們正在探索腸促胰島素和非腸促胰島素途徑作為管理體重以及相關心臟代謝和心腎疾病的多種機制。因此，我們的定位不僅僅是短期減肥，而是提供長期體重管理和健康的瘦體重管理，解決心臟代謝風險和器官保護。

And we think that we'll be able to achieve this by driving forward with multiple mechanisms in combination, thinking about both the incretin pathways, as we've discussed earlier with 5004, and non-incretin pathways, for example, with long-acting amylin. Long-acting amylin, as you can imagine, is a different route of administration and, we think, could offer some additive benefits outside of that, that we're already seeing in the incretin pathway.

我們認為，透過組合多種機制，考慮腸促胰島素途徑（如我們之前討論的 5004）和非腸促胰島素途徑（例如，長效製劑），我們將能夠實現這一目標。正如您可以想像的那樣，長效胰淀素是一種不同的給藥途徑，我們認為，除此之外，我們還可以提供一些額外的好處，我們已經在腸促胰島素途徑中看到了這一點。

So we are accelerating several assets through Phase I. We spoke earlier about 5004. AZD6234 is our long-acting amylin, AZD9550 is our GLP-1 glucagon dual receptor agonist. And both of those latter two molecules are progressing through Phase I. We look forward to sharing the data with you when ready.

因此，我們正在加速通過第一階段的多項資產。後兩個分子都正在進行第一階段。

Thanks, Sharon. Ruud, anything you want to add on?

謝謝，莎倫。路德，你還有什麼要補充的嗎？

No.

不。

So let's move to the next question, Sachin Jain at Bank of America.

那麼讓我們轉向下一個問題，美國銀行的 Sachin Jain。

Sachin Jain, Bank of America. First one is for Dave on Truqap. Strong first quarter, just any initial launch feedback? And then I'm going to try and go to you, Roche talked to about $2 billion for their PI3K yesterday. I wonder if you could talk about the relative profile of your asset related to that and whether you'd go bigger than $2 billion in breast and size the prostate opportunity that Pascal specifically called out?

薩欽‧賈恩 (Sachin Jain)，美國銀行。第一個是 Truqap 上的 Dave。第一季表現強勁，有任何初步發布回饋嗎？然後我會嘗試去找你，羅氏昨天談到了他們的 PI3K 大約 20 億美元。我想知道您是否可以談談您與此相關的資產的相對狀況，以及您是否會在乳房和前列腺方面投入超過 20 億美元的資金，帕斯卡特別指出了這一點？

My second question is for Susan. AVANZAR is due in '25. When do we see the data that informs on your confidence? And what I'm after there is timing of any TROP2 biomarker data. And what should we focus on from TL02 at ASCO that, I think, Daiichi have commented to? And then last quick question for Sharon, eplontersen is now '25-plus. Do you still plan an interim next year?

我的第二個問題是問蘇珊的。 AVANZAR 預計於 25 年上市。我們什麼時候可以看到反映您信心的數據？我所追求的是任何 TROP2 生物標記數據的時間。我認為 Daiichi 對此發表了評論，我們應該關注 ASCO TL02 的哪些內容？最後問 Sharon 一個簡單的問題，eplontersen 現在已經 25 歲以上了。明年你還計劃臨時嗎？

Dave, do you want to start?

戴夫，你想開始嗎？

Sure. Thanks, Sachin, for the questions. So on Truqap, we are really pleased with the launch. And following what was a real positive reception to the presentation of the data, we've seen that the uptake is really moving quite nicely. And I think that uptake in the biomarker population really speaks to the need to extend endocrine-based therapies. We see testing rates are well established by NGS in the U.S., so we've got over 60% on that.

當然。謝謝薩欽提出的問題。因此，我們對 Truqap 的發布感到非常滿意。在對資料呈現的真正積極接受之後，我們發現採用情況確實進展得非常好。我認為生物標記人群的採用確實說明了擴展內分泌治療的必要性。我們看到美國 NGS 的檢測率已經非常完善，因此我們的檢測率超過 60%。

And while there was a previous standard of care with PI3K, we're seeing that rapidly get displaced, though still plenty of opportunity to continue to grow within that segment. So demand is off to a very good start, though I think that there is certainly much more opportunity for us to continue to grow. There's some late line bolus that we're probably seeing within the numbers as well. But again, I think that underlying demand and the indication that we've got is very, very strong.

雖然之前有 PI3K 的護理標準，但我們看到它迅速被取代，儘管該細分市場仍有大量繼續增長的機會。因此，需求有了一個非常好的開始，儘管我認為我們肯定還有更多的機會繼續成長。我們也可能在數字中看到一些後期的推注。但我再次認為，潛在的需求和我們得到的跡象非常非常強勁。

On your specific question also around comparison to the INAVO120 data, from my and our understanding, I think that you first have to take a look at the inclusion criteria. The inclusion criteria are certainly different between that study and 291. In that study, the inclusion criteria only include patients who have progressed during or within 12 months of adjuvant ET completion. It's also limited to the PIK3CA patient population.

關於您關於與 INAVO120 數據比較的具體問題，根據我和我們的理解，我認為您首先必須看看納入標準。研究和 291 之間的納入標準當然不同。它也僅限於 PIK3CA 患者群體。

So if you take a look at 291 within that context, we really have the de novo and the non-early relapsers in the second-line post-CDK4/6 plus AI setting in addition to the fast progressors. And I see more like 3/4 of the patients falling into this de novo, non-early relapser population. So I'm enthusiastic about the opportunity in breast cancer. I'm enthusiastic about the opportunity also in prostate cancer. And I think you put these two together, and we've got the potential for Truqap to be a multi-blockbuster.

因此，如果你在這種背景下觀察 291，除了快速進展者之外，我們在二線後 CDK4/6 加 AI 設定中確實還有新發者和非早期復發者。我發現大約 3/4 的患者屬於新發非早期復發族群。所以我對乳癌的機會充滿熱情。我對前列腺癌領域的機會也充滿熱情。我認為將這兩者放在一起，我們就有可能讓 Truqap 成為一款重磅炸彈。

Susan?

蘇珊？

Okay. Thanks, Dave. So for AVANZAR, again, yes, as I said, the trial is going well. But the TROP2 biomarker data, I expect that we would be able to share those data at a congress within the next 12 months certainly. And as far as ASCO goes, one thing beyond the lung cancer data that I would encourage you to try take a look at is the I-SPY 2 data, which is a neoadjuvant study in breast cancer, again looking at the combination of dapa and Imfinzi in that setting.

好的。謝謝，戴夫。因此，對於 AVANZAR 來說，是的，正如我所說，試驗進展順利。但是 TROP2 生物標記數據，我預計我們肯定能夠在未來 12 個月內的一次大會上分享這些數據。就 ASCO 而言，除了肺癌數據之外，我鼓勵您嘗試查看 I-SPY 2 數據，這是一項針對乳腺癌的新輔助研究，再次關注 dapa 和Imfinzi 在那個環境中。

So I think we continue to be happy with the profile that we're seeing for dapa plus IO across the first-line settings in lung cancer. The safety is looking very reasonable because we've got many patients now enrolled into those first-line settings. And again, as we move this combination into the earlier lines in settings like the new adjuvant setting, I think both the safety and the efficacy profile look encouraging. So that's what I would point you to at ASCO.

因此，我認為我們仍然對在肺癌一線治療中看到的 dapa 加 IO 的概況感到滿意。安全性看起來非常合理，因為我們現在有許多患者進入了這些第一線機構。再說一次，當我們將這種組合轉移到新輔助劑等早期治療方案中時，我認為安全性和療效看起來都令人鼓舞。這就是我在 ASCO 向您指出的。

Thanks, Susan.

謝謝，蘇珊。

And then your last question, I believe, was about the eplontersen CARDIO-TTRansform trial and our expected timeline for readout on that one. So as I mentioned earlier today, we remain extremely optimistic and excited about the potential for this molecule. And I showed you some early data that came from our NEURO-TTRansform study, which demonstrated a benefit on cardiac structure and function, which gives us additional confidence in the potential for the molecule as we walk through the CARDIO-TTRansform study.

我相信你的最後一個問題是關於 eplontersen CARDIO-TTRansform 試驗以及我們對該試驗的預期讀出時間表。正如我今天早些時候提到的，我們對這種分子的潛力仍然非常樂觀和興奮。我向您展示了來自我們的 NEURO-TTRansform 研究的一些早期數據，這些數據證明了對心臟結構和功能的益處，這讓我們在進行 CARDIO-TTRansform 研究時對該分子的潛力更有信心。

This molecule has the potential to be a best-in-class and transform care for patients with amyloidosis. So to that end, we would like to give this trial the best chance for success and to be able to read the full trial data at the 140 week time point. That in mind, we'll continue to scan the competitive landscape and make the appropriate decisions as we move forward.

該分子有潛力成為同類最佳藥物，並改變澱粉樣變性患者的照護。為此，我們希望為該試驗提供最好的成功機會，並能夠在 140 週的時間點讀取完整的試驗數據。考慮到這一點，我們將繼續審視競爭格局，並在前進過程中做出適當的決定。

Thank you, Sharon. And Sachin, on part of your question, we never comment, as you know, on interim analysis. So of course, we will not do any -- we will not do it here either.

謝謝你，莎倫。薩欽，關於你的問題的一部分，正如你所知，我們從未對中期分析發表評論。所以當然，我們不會做任何事——我們也不會在這裡做。

Next question is Tim Anderson at Wolfe.

下一個問題是沃爾夫的蒂姆·安德森。

Couple of questions, on dato, just an update on your thinking on the lung filing in the U.S. If the overall survival data only continues to be directionally supportive and doesn't fall a little bit upper-end threshold of 1, is that enough to get U.S. approval? And then what would that mean for ex U.S. approval? And when is that next survival look going to incur?

有幾個問題，關於 dato，只是您對美國肺部歸檔的看法的最新情況。那麼這對於獲得美國批准意味著什麼？下一次生存之旅什麼時候發生？

And then the second question is just emerging markets. China, obviously, has slowed from years ago for lots of companies. What really stands out in your results is that non-China emerging market segment, which is substantial now, continuing to grow. But it's just not clear to me what the drivers of that are in terms of geographies and products and, therefore, what the future growth expectations should be in those non-China markets. So if you could add some commentary, that would be helpful.

第二個問題是新興市場。顯然，對許多公司來說，中國的發展速度比幾年前放緩。你們的結果中真正引人注目的是非中國新興市場領域，目前該市場規模很大，並且持續成長。但我不清楚地域和產品方面的驅動因素是什麼，因此，這些非中國市場的未來成長預期應該是什麼。因此，如果您可以添加一些評論，那將會很有幫助。

Thank you. So maybe, Susan, you could take the first one?

謝謝。那麼，蘇珊，你也許可以選擇第一個？

Yes. So for Dato-DXd TROPION-Lung01 study, obviously, we've announced that we have filed, obviously, for all regulatory authorities, OS in lung cancer is an important component that they'll want to look at. We said that the timing of the OS data cut is around the middle of the year.

是的。因此，對於 Dato-DXd TROPION-Lung01 研究，顯然，我們已經宣布，我們已經向所有監管機構提交了申請，顯然，肺癌中的 OS 是他們想要研究的一個重要組成部分。我們說過作業系統資料削減的時間是在年中左右。

As you know already that we saw an overall trend in favor of OS on the dato arm in the ITT. But what we also saw is in the non-squamous group, a more positive trend with the upper end of (inaudible) crossing 1. So we were looking and hoping that we'll see both of those continue or improve. And I think that will be an important piece for the regulatory authorities to look at.

如您所知，我們看到了 ITT 中 dato 部門支援作業系統的整體趨勢。但我們在非鱗狀細胞組中也看到了一種更積極的趨勢，其上限為（聽不清楚）交叉1。我認為這將是監管機構需要關注的重要部分。

Thanks, Susan. And the second one, maybe Leon, who is online, I believe, Leon, can you actually comment on that one?

謝謝，蘇珊。第二個，也許萊昂，他在線，我相信，萊昂，你真的能評論一下那個嗎？

Yes. I think actually across all geographic, AstraZeneca emerging market has been growing rapidly and almost no exception. And of course, there is some currency depreciation in certain countries, but overall, still very, very strong growth. And we are also in line with the global new product launch. I think Tagrisso, Farxiga, these Oncology brands and also Rare Disease as a new growth driver is also doing very well across the emerging markets.

是的。我認為實際上在所有地區，阿斯特捷利康新興市場都在快速成長，幾乎也不例外。當然，某些國家的貨幣有所貶值，但整體而言，成長仍然非常非常強勁。而且我們也配合全球新品發表會。我認為Tagrisso、Farxiga這些腫瘤品牌以及罕見疾病作為新的成長動力在新興市場也表現出色。

And all in all, on top of that, the LOE, patent-expired products, legacy products, they are still quite -- we spend very little resource and also growing nicely to support as a cash cow, our new launches. And also across the region, we are speeding up approval in many emerging markets. So we launched new products much earlier than before.

總而言之，最重要的是，LOE、專利過期的產品、遺留產品，它們仍然相當——我們花費很少的資源，並且增長良好，以支持我們的新產品作為搖錢樹。在整個地區，我們正在加快許多新興市場的審批速度。所以我們推出新產品的時間比以前早很多。

Thanks, Leon. So net-net, Tim, you have really two factors. One is we have a very strong commercial footprint in those countries. Now we are actually the #1 pharma company in the international region. And so we are leveraging this strong commercial footprint across all subregions. The second factor is we actually, a couple of years ago, invested more resources into a specific international region, regulatory team.

謝謝，萊昂。所以，提姆，網路網絡，你確實有兩個因素。一是我們在這些國家擁有非常強大的商業足跡。現在我們實際上是國際地區排名第一的製藥公司。因此，我們正在利用在所有次區域的強大商業足跡。第二個因素是，我們實際上在幾年前向特定的國際區域監管團隊投入了更多資源。

And that team has been fast-tracking filing and approvals of new products in those countries who historically were falling behind the priority geographies. And now we still launch after the U.S. and Europe or Japan in those countries but not that much later. And we are still working on accelerating this. So those two factors are really the most important growth drivers.

該團隊一直在那些歷史上落後於優先地區的國家/地區快速追蹤新產品的備案和批准。現在我們仍然在美國、歐洲或日本之後在這些國家推出，但不會晚太多。我們仍在努力加速這一進程。因此，這兩個因素確實是最重要的成長動力。

The next question, I think, is Mattias Häggblom at Handelsbanken.

我認為下一個問題是德國商業銀行的 Mattias Häggblom)。

Mattias Häggblom, Handelsbanken. Two questions, please. So firstly, on Dato-DXd, you initiated a couple of additional Phase III programs during the quarter with your partner. So what makes you so confident to continue to invest into these programs? Or asked perhaps differently, with investor communities still skeptical today to this, what in particular is it you see that investors may miss?

Mattias Häggblom，德國商業銀行。請教兩個問題。首先，在 Dato-DXd 上，您與合作夥伴在本季度啟動了幾個額外的第三階段計劃。那麼是什麼讓您如此有信心繼續投資這些項目呢？或者可能會提出不同的問題，因為投資者群體今天仍然對此持懷疑態度，您認為投資者可能會錯過什麼？

And then secondly, as one of few companies with both bispecific antibodies as well as cell therapy capabilities in-house, can you talk about how you think about engaging these tools into autoimmune disease, whether it's emerging early data from both sets of technologies that looks promising?

其次，作為少數同時擁有雙特異性抗體和內部細胞治療能力的公司之一，您能否談談您如何考慮將這些工具用於自體免疫疾病，無論是從兩組技術中出現的早期數據看起來有希望？

Thanks, Mattias. The first question, I think, would go to Susan. And the second, Sharon, you'll take that one, okay.

謝謝，馬蒂亞斯。我認為第一個問題應該要問蘇珊。第二個，莎倫，你就拿那個吧，好吧。

Yes. So thanks for asking the question about Dato-DXd. So yes, we have announced that we're starting TROPION-Lung10, which is a combination with rilvegostomig, our PD-1, TIGIT bispecific, and dato compared to pembro in locally advanced first-line non-small cell lung cancer. And again, that is a program where we're going to be looking at this activity in a biomarker-selected group as well. But it also includes the ability to compare rilvegostomig directly with pembro in that setting.

是的。感謝您詢問有關 Dato-DXd 的問題。所以，是的，我們已經宣布，我們正在啟動TROPION-Lung10，它是與rilvegostomig、我們的PD-1、TIGIT 雙特異性藥物和dato 的組合，與pembro 相比，治療局部晚期一線非小細胞肺癌。再說一遍，在這個計畫中，我們還將在生物標記選擇的小組中研究這項活動。但它還包括在該設定中直接將 rilvegostomig 與 pembro 進行比較的能力。

So I think what underpins our confidence there is both the combinability with IO that we have seen in different settings, the potential for the -- some added efficacy for the addition of the TIGIT mechanism of action as part of this bispecific within the PD-L1 greater than 50% patient population as well. And we think that this can be a winning combination in that setting.

因此，我認為支撐我們信心的是我們在不同環境中看到的與 IO 的組合性，以及添加 TIGIT 作用機製作為 PD-L1 內雙特異性的一部分的一些額外功效的潛力。患者群。我們認為，在這種情況下，這可能是一個成功的組合。

The other important study that I'd draw your attention to is the TROPION-Lung14 study, this is a combination of Dato-DXd and Tagrisso in the first-line non-squamous EGFR-mutant non-small cell lung cancer. And again, this builds on both safety and efficacy data that we've seen from the ORCHARD platform study that we have in a post-third generation EGFR inhibitor patient population in the EGFR mutant and also the safety and combinability for that combination. So that's what gives us confidence.

我提請您注意的另一項重要研究是 TROPION-Lung14 研究，這是 Dato-DXd 和 Tagrisso 聯合治療一線非鱗狀 EGFR 突變非小細胞肺癌的研究。同樣，這建立在我們從 ORCHARD 平台研究中看到的 EGFR 突變體第三代 EGFR 抑制劑患者群體的安全性和有效性數據以及該組合的安全性和可組合性的基礎上。這就是給我們信心的原因。

As you may have seen in the TROPION-Lung05 data that was published, there's actually really good activity for Dato-DXd within the EGFR-mutant population. And given the FLAURA2 data, which we've also seen, I think that, that also builds confidence in the ability to combine Tagrisso with chemotherapy and directed agents. And so I think this has the opportunity to further build on the data that we had from FLAURA2 and the data from ORCHARD and really have a winning combination in the first-line setting for EGFR-mutant non-small cell lung cancer.

正如您可能在已發布的 TROPION-Lung05 數據中看到的那樣，Dato-DXd 在 EGFR 突變人群中實際上具有非常好的活性。鑑於我們也看到了 FLAURA2 數據，我認為這也增強了人們對 Tagrisso 與化療和定向藥物相結合的能力的信心。因此，我認為這有機會進一步建立在我們從 FLAURA2 獲得的數據和來自 ORCHARD 的數據的基礎上，並且在 EGFR 突變非小細胞肺癌的一線治療中真正擁有一個成功的組合。

Thank you, Susan. Sharon?

謝謝你，蘇珊。莎倫？

Sure. So thank you very much for the question about cell therapy and bispecifics in autoimmune disease because I think it's a really interesting topic that has become a key focus for us. As we think about how we manage diseases of immune disregulation, we are moving from managing symptoms to modifying disease by adding the causality of disease. And the mechanisms that you mentioned, cell therapy and bispecific molecules, are two excellent modalities that allow us to really address the causality of disease.

當然。非常感謝您提出有關自體免疫疾病中的細胞療法和雙特異性藥物的問題，因為我認為這是一個非常有趣的話題，已成為我們關注的焦點。當我們思考如何管理免疫失調疾病時，我們正在從管理症狀轉向透過增加疾病的因果關係來改變疾病。您提到的機制，細胞療法和雙特異性分子，是兩種極好的方式，使我們能夠真正解決疾病的因果關係。

So to that end, we have invested in internal capabilities but also accelerated our ambition with recent acquisitions. As you saw, we very recently closed an acquisition of Gracell, which brought to us some, I think, leading capabilities that allow us really accelerate our ambitions in cell therapy for patients with autoimmune disease. And specifically, Gracell has a biCAR-T, which they have used to complete an investigator-initiated trial in China for patients with systemic lupus erythematosus, or SLE. And we look forward to sharing this data at an upcoming medical conference.

為此，我們投資了內部能力，但也透過最近的收購加速了我們的雄心壯志。正如您所看到的，我們最近完成了對 Gracell 的收購，我認為這給我們帶來了一些領先的能力，使我們能夠真正加速我們在自體免疫疾病患者細胞治療方面的雄心壯志。具體來說，Gracell 擁有 biCAR-T，他們已用它在中國完成了一項由研究者發起的針對系統性紅斑狼瘡 (SLE) 患者的試驗。我們期待在即將召開的醫學會議上分享這些數據。

But I think it's safe to say that the data that we have seen across the patients treated is at least as compelling as anything that we have seen in the published literature, and it gives us a lot of excitement and optimism about how we may be able to address SLE for patients moving forward. At the same time, we're also investing in our internal platforms for creating T-cell engagers, which we think also could be a very powerful modality in the autoimmune space.

但我認為可以肯定地說，我們在接受治療的患者中看到的數據至少與我們在已發表的文獻中看到的任何數據一樣令人信服，並且它讓我們對如何能夠做到這一點感到非常興奮和樂觀為患者解決 SLE 問題。同時，我們也投資於創建 T 細胞參與者的內部平台，我們認為這也可能是自體免疫領域的非常強大的模式。

Thank you, Sharon. Mark Purcell at Morgan Stanley.

謝謝你，莎倫。摩根士丹利的馬克·珀塞爾。

Two questions. The first one, the U.S. oral Oncology products, the product sales there were very strong in the quarter. Could you help us understand the impact of treatment initiation dynamics and potential changes in affordability?

兩個問題。第一個是美國口腔腫瘤產品，該季度產品銷售非常強勁。您能否幫助我們了解治療啟動動態的影響以及負擔能力的潛在變化？

And then secondly, on the Fusion Pharmaceuticals platform, for FPI-2265, can you help us understand your plans for moving into sort of pre-taxane setting? Would you do a head-to-head trial there versus Pluvicto potentially combined with PARP-1, obviously, understanding that the post-Pluvicto opportunity itself has blockbuster potential anyway?

其次，在 Fusion Pharmaceuticals 平台上，對於 FPI-2265，您能否幫助我們了解您進入紫杉烷前環境的計劃？顯然，你會在那裡與 Pluvicto 可能與 PARP-1 結合進行一對一的試驗嗎？

So Mark, thanks. I'll take the first question, probably Susan on the second. I mean, I think the first important piece is that within the quarter on our oral oncolytics, particularly with Calquence and Tagrisso, we saw strong market share performance, i.e., Calquence remaining the leading BTKi in frontline CLL and strong continued demand growth for Tagrisso in adjuvant and frontline and encouraging early FLAURA2 launch.

所以馬克，謝謝。我將回答第一個問題，第二個問題可能是蘇珊。我的意思是，我認為第一個重要的部分是，在本季度內，我們的口服溶瘤藥物，特別是Calquence 和Tagrisso，我們看到了強勁的市場份額表現，即Calquence 仍然是一線CLL 中領先的BTKi，並且對Tagrisso 的需求持續強勁增長。

With that said, also we do see early encouraging trends of lower abandonment and improved access due to affordability, though it really is too early to quantify. And of course, recall, Mark, that in 2024, there's no added liability associated with Part D, whereas it comes in, in '25. But we'll continue to keep updated on how those dynamics on affordability evolve over the course of the year.

話雖如此，我們也確實看到了早期令人鼓舞的趨勢，即由於負擔能力而導致放棄率降低和獲得率提高，儘管現在量化還為時過早。當然，馬克，請記住，到 2024 年，不會再有與 D 部分相關的額外責任，而它是在 25 年引入的。但我們將繼續關注這一年來負擔能力動態的變化。

And Mark, on your second question, the deal hasn't closed and so we are not able to comment at this point in time. Sorry about this. And hopefully, we can give you an answer pretty soon.

馬克，關於你的第二個問題，交易尚未完成，因此我們目前無法發表評論。為此事道歉。希望我們能盡快回覆您。

Richard Parkes at Exane.

Exane 的理查德·帕克斯。

Firstly, sometimes when speaking to investors, I get the perception there's a feeling that AstraZeneca is maybe spreading itself too thinly with expansion into vaccine, cell therapy, radioligand. Just wondering how you respond to that and whether you see any risk of the organization losing focus and how you're thinking about some of those investments in new platforms. It feels to me like it's more you're just thinking about that the day after tomorrow. So that would be very helpful.

首先，有時在與投資者交談時，我感覺阿斯特捷利康在向疫苗、細胞療法和放射性配體領域擴張時，業務範圍可能過於分散。只是想知道您對此有何反應，以及您是否認為組織失去焦點的風險以及您如何考慮對新平台的一些投資。對我來說，你更多的是在後天思考這個問題。所以這會很有幫助。

And then on Airsupra, could you just talk a little bit more about the opportunity you're seeing? Obviously, we're seeing some very large drugs in that category in the past. So just thinking about how your thinking has evolved on the opportunity since the launch.

然後在 Airsupra 上，您能多談談您看到的機會嗎？顯然，我們過去在該類別中看到過一些非常大的藥物。因此，想想自推出以來您的想法是如何隨著這個機會而演變的。

Thanks, Richard. Let me try the first question. And maybe, Ruud, you could cover the second one. So the first question, I think first point is, I'm sure you've realized, we have a very, very strong team. And people are very focused on Oncology, BioPharma, Rare Disease and managing their portfolios.

謝謝，理查。讓我嘗試第一個問題。也許，路德，你可以討論第二個問題。所以第一個問題，我認為第一點是，我相信你已經意識到，我們有一個非常非常強大的團隊。人們非常關注腫瘤學、生物製藥、罕見疾病和管理他們的投資組合。

Second point is we are now kind of a $50 billion company. So you really need a portfolio to continue growing. And I think this is one of our strengths. We're not depending on two or three products. We have a portfolio of products that are driving our growth. And we can actually highlight that better to you at the Investor Day very soon.

第二點是我們現在是一家價值 500 億美元的公司。所以你確實需要一個投資組合來繼續成長。我認為這是我們的優勢之一。我們不依賴兩三種產品。我們擁有推動我們成長的產品組合。事實上，我們很快就能在投資者日向您更好地強調這一點。

Third point I would make is that, actually, this portfolio actually gives us the opportunity to combine. And again, that's what we want to highlight during the Investor Day. We're in a unique position to combine in Oncology across ADCs, bispecific potentially -- bispecific IO potentially in the long run, take an approach to solid tumors to address the tumor with a combination of ADCs and bispecific and follow this with TCEs or cell therapy. In the cardiovascular space, Sharon has covered it, we can combine across the GLP-1 and PCSK9 or the other agents, the PARP, of course. So I think these are the things that actually help us.

我要說的第三點是，實際上，這個投資組合其實給了我們合併的機會。這也是我們想在投資人日強調的一點。我們處於獨特的地位，可以將ADC 與雙特異性潛在的腫瘤學結合起來——從長遠來看，雙特異性IO 可能是潛在的，採取一種實體瘤方法，透過ADC 和雙特異性的組合來治療腫瘤，並隨後與TCE 或細胞一起使用治療。在心血管領域，Sharon 已經介紹過，我們可以將 GLP-1 和 PCSK9 或其他藥物（當然還有 PARP）結合。所以我認為這些才是真正對我們有幫助的事。

On the vaccine front, I think there's sometimes a misperception of what we're trying to do. We're not trying to build a vaccine business like vaccine companies have. We are actually targeting vaccines that will be synergistic, strategic to our -- vaccine and antibodies, by the way, that are synergistic to Oncology or respiratory disease, products that will protect patients from exacerbations of COPD or asthma, products that would protect patients from COVID or flu infections, if there are, say, cancer patients, blood cancers in particular.

在疫苗方面，我認為有時人們對我們正在努力做的事情有誤解。我們並不想像疫苗公司那樣建立疫苗業務。實際上，我們的目標是對我們的疫苗和抗體具有協同性和戰略性的疫苗，順便說一下，它們對腫瘤或呼吸道疾病有協同作用，這些產品將保護患者免受慢性阻塞性肺病或哮喘的惡化，產品將保護患者免受慢性阻塞性肺病或氣喘的影響。

So this is really what we are trying to do, always try to be implementing a sort of a strategic synergy across our portfolio and leverage our expertise and our strengths in various places. So I don't think we are too thin and then -- too thinly spread. And the challenge and the opportunity in our industry is always to be able to think about today but also the long term.

因此，這確實是我們正在努力做的事情，始終嘗試在我們的投資組合中實施某種策略協同作用，並利用我們在各個方面的專業知識和優勢。所以我不認為我們太弱，然後——太分散了。我們產業的挑戰和機會始終是既要考慮今天，也要考慮長遠。

It would be very easy, quite frankly, or easier to focus on the next 4, 5 years. But we also have to think about what is going to shape the medicine in 5 to 10 years so that this company remains a growth organization, not only in the next few years but in the long run. And so that's always the challenge is really to manage our near term, long term. But also it's an opportunity that if we do that well and if we play our hand very well, we can be very differentiated as a company. So Ruud, over to you.

坦白說，專注於未來 4、5 年會很容易，或者說更容易。但我們還必須考慮如何在 5 到 10 年內塑造該藥物，以便該公司不僅在未來幾年而且從長遠來看仍然是一個成長型組織。因此，管理我們的近期和長期目標始終是真正的挑戰。但這也是一個機會，如果我們做得好並且發揮得很好，我們作為一家公司就可以實現差異化。路德，交給你了。

Yes, of course. And thank you so much for the question, Richard. So first of all, Airsupra is quite a unique product in the United States because it's the first rescue therapy for asthma patients above 18 years of age. It's a very substantial market, the short-acting beta agonist market. Just to give you a little bit of context, roughly 35 million inhalers are prescribed every year for the 18-plus population in the United States. So the volumes are very, very substantial. And we truly believe that we have a product in place which can change the treatment paradigm of as-needed rescue medication in the U.S.

是的當然。非常感謝你提出這個問題，理查德。首先，Airsupra 在美國是一個相當獨特的產品，因為它是第一個針對 18 歲以上氣喘患者的救援療法。這是一個非常龐大的市場，即短效β受體激動劑市場。為您提供一些背景信息，美國每年為 18 歲以上人口開出大約 3500 萬個吸入器。所以數量非常非常大。我們堅信，我們的產品可以改變美國按需救援藥物的治療模式。

Of course, it's still early days. But the fact that we already see a very substantial number of scripts every week plus that more and more physicians are prescribing it, I truly believe that over the next few years that this product will become a blockbuster molecule. And equally, we're also looking for other opportunities in other geographies in the world. Especially in the Middle East, we see good opportunities to launch the product there as well in the next few months. So all in all, very bullish regarding the forecast and the potential of this product moving forward.

當然，現在還為時過早。但事實上，我們每週都會看到大量的處方，加上越來越多的醫生開出該藥的處方，我堅信，在未來幾年內，該產品將成為一種重磅炸彈分子。同樣，我們也在世界其他地區尋找其他機會。特別是在中東，我們看到了在未來幾個月內推出產品的良好機會。總而言之，我們非常看好該產品未來的預測和潛力。

Thanks, Ruud. The next question is from Christopher Uhde at SEB.

謝謝，路德。下一個問題來自 SEB 的 Christopher Uhde。

Can you hear me?

你聽得到我嗎？

Yes.

是的。

Good. So yes, I guess, first question is a lot of the key sort of Part D products and, I guess, the U.S. in general, had really strong performance. Can you quantify how big a headwind the typical U.S. coverage resets amounted to and what factors beyond strong demand help explain why Q1 was so strong? And roughly, how much did they collectively contribute then to top line growth, noting that, for example, Farxiga, one of those factors was the authorized generic?

好的。所以，是的，我想，第一個問題是很多關鍵的 D 部分產品，我想，美國總體上表現非常強勁。您能否量化美國保險覆蓋率重置的典型阻力有多大？粗略地說，他們當時對營收成長總共貢獻了多少，並指出，例如 Farxiga，這些因素之一就是授權的仿製藥？

And then my second question, which pipeline events for the rest of 2024 do you get most excited about? And which do you think The Street might be underappreciating? And what are we missing, if so? And if I could sneak in the last one, you said M&A will slow down earlier today. I've read is you've got most of what you need. I note you don't have a KRAS though. Perhaps you could tell us what your thoughts are around KRAS and why that isn't in your portfolio?

然後是我的第二個問題，2024 年剩餘時間裡哪些管道事件讓您最興奮？您認為《華爾街日報》可能低估了哪些內容？如果是的話，我們還缺少什麼呢？如果我可以偷偷地講最後一篇，您說今天早些時候併購將會放緩。我讀到你已經得到了你需要的大部分東西。我注意到您沒有 KRAS。也許您可以告訴我們您對 KRAS 的想法以及為什麼它不在您的投資組合中？

Thanks, Christopher. So maybe, Ruud, you could take the first one and I'll try to address the others.

謝謝，克里斯多福。所以也許，Ruud，你可以選擇第一個，我會嘗試解決其他問題。

Yes, yes, an excellent question. We have seen very strong growth in the United States for both Farxiga and Symbicort. It's driven by two different factors. First of all, we have launched an authorized generic of Farxiga in the United States for the option for patients to have a lower cost option as well. And so far, we are very pleased with that introduction of this new -- not new medicine but this new offer to patients. And of course, we will not know until, let's say, a few quarters more how the products will both perform. But so far, the feedback has been extremely strong.

是的，是的，這是一個很好的問題。我們看到 Farxiga 和 Symbicort 在美國的成長非常強勁。它由兩個不同的因素驅動。首先，我們在美國推出了 Farxiga 的授權仿製藥，為患者提供了更低成本的選擇。到目前為止，我們對這種新藥物的推出感到非常高興——不是新藥，而是為患者提供的新產品。當然，我們要等到幾個季度後才能知道這兩款產品的表現如何。但到目前為止，反饋非常強烈。

Equally, I think it's important that looking at Farxiga in totality that the growth across the world is extremely strong on the basis of the CKD and heart failure indications. And there's no reason to believe that, that will slow down anytime soon. So that's good news. Symbicort, we have closed our list price, the so-called reg price in the United States, like other competitors have done as well. So we need to see how that will evolve in the next few quarters. So it's a little bit of a new dynamic in Part D, let's say, in quarter 1 for our products. But all in all, a very nice first few months, and we will monitor it very closely, of course, moving forward.

同樣，我認為重要的是，從整體上看 Farxiga 在 CKD 和心臟衰竭適應症的基礎上在全球範圍內的增長非常強勁。沒有理由相信這種情況會很快放緩。這是個好消息。 Symbicort，我們已經關閉了我們的標價，即美國所謂的監管價格，就像其他競爭對手所做的那樣。因此，我們需要看看未來幾季將如何發展。因此，對於我們的產品來說，D 部分（例如第一季）有一些新的動態。但總而言之，前幾個月非常好，我們當然會非常密切地監控它，並繼續前進。

Thanks, Ruud. Let me try the other two questions quickly in the interest of time, is the pipeline and what is more exciting until 2030. Christopher, I would again invite you to join us in Cambridge. We are offering free tickets, a visit to beautiful Cambridge. And I'm sure we'll find a way to give you a nice lunch, too.

謝謝，路德。為了節省時間，讓我快速嘗試另外兩個問題，即管道問題以及 2030 年之前更令人興奮的問題。我們提供免費門票，參觀美麗的劍橋。我相信我們也會找到一種方法為您提供一頓美味的午餐。

On the M&A, I said it will slow down. It doesn't mean it will be 0. What I meant to say earlier in terms of slowing down is from a technology, from a platform viewpoint, I think we have acquired and built most of what we need for now and we need to execute on what we've got. But it doesn't mean, of course, BD will come down to 0. And in terms of the specific KRAS question, I won't answer this one. But we have our own internal program. And we can discuss some of those things again in Cambridge.

關於併購，我說會放緩。這並不意味著它會是0。擁有的而言。但這當然並不意味著 BD 會降到 0。但我們有自己的內部計劃。我們可以在劍橋再次討論其中一些事情。

So I'll move to Eric Le Berrigaud at Stifel.

所以我將轉向 Stifel 的 Eric Le Berrigaud。

First question to come back on Farxiga and Symbicort in the U.S., maybe more specifically on Farxiga, is there any way we can get any idea about the one-off that could be into the Q1 numbers with inventory buildup for the authorized generic? And on Symbicort, in the context of the drug being genericized in the U.S., we're expecting sales to go down. It was up 28% in Q1. What could be the dynamic for U.S. Symbicort for the full year '24?

關於 Farxiga 和 Symbicort 在美國的第一個問題，也許更具體地說是關於 Farxiga，我們是否可以透過任何方式了解授權仿製藥庫存累積可能進入第一季資料的一次性資料？對於 Symbicort，在該藥物在美國進行仿製藥的背景下，我們預計其銷售量將會下降。第一季成長了 28%。美國 Symbicort 24 年全年的動態如何？

And then a more general question, we see more and more companies simplifying, streamlining the organization by combining the different divisions in one single, like vaccine with pharma or onco with the rest of pharma. And you're still operating with different entities like onco, BioPharma, Alexion, V&I. Could you maybe summarize maybe your thinking about doing things differently, but the benefit of doing the way you do and benefits versus risk and complexity?

然後是一個更普遍的問題，我們看到越來越多的公司透過將不同部門合併為一個部門來簡化組織，例如疫苗與製藥公司或腫瘤與製藥公司的其他部門。而且您仍在與不同的實體合作，例如 onco、BioPharma、Alexion、V&I。您能否總結一下您對以不同方式做事的想法，以及按照您的方式做事的好處以及收益與風險和複雜性的比較？

Yes. So I mean, let me start with the other question. And Ruud, you can cover Farxiga and Symbicort in the U.S. It's not still, it's actually we moved to that structure not that long ago, a few years, of course. But in our industry, 2, 3 years is not a long -- or 4 years is not a long time. As for the (inaudible) and the importance of being focused, on the one hand, people say, "You have too much." On the other hand, we say, "Well, put everything together." So I think the reason why we can succeed with our portfolio and leverage that portfolio is because, indeed, we are focused.

是的。所以我的意思是，讓我從另一個問題開始。 Ruud，你可以在美國報導 Farxiga 和 Symbicort。但在我們這個行業，2年、3年不算長，或4年也不算長。至於（聽不清楚）和專注的重要性，一方面，人們說，“你擁有的太多了。”另一方面，我們說：“好吧，把所有東西放在一起。”因此，我認為我們能夠透過我們的投資組合取得成功並利用該投資組合的原因是因為我們確實專注。

We are focused on Oncology, BioPharma and Rare Disease. And anybody who's operated in Oncology, I think, would hopefully agree with me that Oncology is very specific, this is very specific. And just the same as cardiovascular, you need to build capabilities. And you can only do this if you do two things: first of all, recruit the right talent to understand the environment they are in; and secondly, create a culture and a community where people feel they work together to the same goal.

我們專注於腫瘤學、生物製藥和罕見疾病。我想，任何從事腫瘤學手術的人都會希望同意我的觀點，腫瘤學是非常具體的，這是非常具體的。就像心血管一樣，你需要培養能力。做到兩點，你才能做到這一點：首先，招募合適的人才，了解他們所處的環境；其次，創造一種文化和社區，讓人們感覺到他們為了同一個目標而共同努力。

In the case of cancer, the goal is eliminate cancer as a cause of death. And every community in the company has this total focus, that shared purpose. And that's what drives people. People come to work to make a difference and make a difference in the field they are in and the field they love typically. So I think this is really the reason why we can actually succeed. And we'll intend to keep that structure as it is. Ruud, over to you.

就癌症而言，目標是消除癌症這個死亡原因。公司中的每個社區都有這個共同的焦點和共同的目標。這就是人們的動力。人們參與工作是為了做出改變，並在他們所在的領域和他們通常喜歡的領域做出改變。所以我認為這確實是我們能夠真正成功的原因。我們打算保持該結構不變。路德，交給你了。

Yes. Thank you, once again, Eric, for the two questions. First of all, once again, let me remind you about the U.S. is a very important market for Farxiga, there's no doubt. But it only represents less than 25% of our global sales. And we are very pleased to see that the brand is growing extremely fast, not only in the United States but across all the other geographies.

是的。再次感謝埃里克提出的兩個問題。首先，我再次提醒大家，毫無疑問，美國對 Farxiga 來說是一個非常重要的市場。但它僅占我們全球銷售額的不到 25%。我們非常高興地看到該品牌不僅在美國而且在所有其他地區都在快速成長。

Specifically to your question, can you provide a split between the authorized generic and the brands? The short answer is we're not going to do that. But equally, of course, you can look at the script volume. If you analyze the script volume of Farxiga, it's the Farxiga brand as well as the authorized generic. Now whether the strong initial growth will continue moving forward, we need to see that. We simply don't know.

具體到你的問題，你能提供授權仿製藥和品牌之間的差異嗎？簡短的回答是我們不會這樣做。但同樣，當然，你可以看看腳本量。如果分析Farxiga的腳本量，它是Farxiga品牌，也是授權仿製藥。現在強勁的初始成長是否會繼續向前發展，我們需要看看。我們根本不知道。

Equally for Symbicort, Symbicort, it's quite amazing that after 20 -- more than 20 years of initial launch that Symbicort is still annualizing more than $2 billion a year, very fast growth again in the emerging markets but also equally this year so far in the United States. And it's heavily driven by the fact that we have an authorized generic available as well as we have also lowered our WAC, the so-called list price, in the United States.

同樣對 Symbicort 來說，Symbicort 令人驚訝的是，在首次推出 20 多年之後，Symbicort 的年銷售額仍然超過 20 億美元，在新興市場再次實現快速增長，而且今年迄今為止在全球市場也同樣如此。美國。這在很大程度上是因為我們擁有授權的仿製藥，而且我們也降低了美國的 WAC（所謂的標價）。

So it becomes more affordable for many patients. And once again, whether that will continue during the course of the year, it needs to be seen. But so far, it's very pleasing to see that both brands are off of a very strong start in the United States as well as outside of the United States.

因此，對於許多患者來說，它變得更加負擔得起。再說一遍，這種情況是否會在今年持續下去，還需要拭目以待。但到目前為止，我們非常高興地看到這兩個品牌在美國以及美國以外的地區都有一個非常強勁的開局。

Thanks, Ruud. Maybe I would add that everybody talks about one-offs. And to be honest, I'm not sure why there's such a focus on one-offs. If you look at Farxiga in the U.S., Q4 sales were $450 million, Q1 sales are $470 million. And if you look at the trend over the last few quarters, we've had a very strong trend.

謝謝，路德。也許我要補充一點，每個人都在談論一次性的事情。說實話，我不知道為什麼要如此專注於一次性的事情。如果你看看美國的 Farxiga，第四季的銷售額為 4.5 億美元，第一季的銷售額為 4.7 億美元。如果你看看過去幾季的趨勢，我們有一個非常強勁的趨勢。

And if you marry that or combine this with the prescription trend that Ruud was talking about, there's certainly a little bit of a stock-up. But it is not really what drives the trend for Farxiga. It's a very strong trend, not only in the U.S. but across the world. So every country is behaving the same way. We have very strong uptake in kidney disease, heart disease, diabetes, et cetera.

如果你將其與路德所說的處方趨勢結合起來，那麼肯定會有一點庫存。但這並不是 Farxiga 趨勢的真正驅動力。這是一個非常強勁的趨勢，不僅在美國，而且在全世界。所以每個國家的行為方式都是一樣的。我們對腎臟疾病、心臟病、糖尿病等有很強的了解。

The next one is Steve Scala at Cowen.

下一位是 Cowen 的 Steve Scala。

I have two questions. First, D-B06 hit its primary completion in March. Is the data in-house? And is that underpinning your confidence? And second, why is there, what seems to be, a long delay in presenting the oral GLP-1 and oral PCSK9 data? I could think of four possible reasons.

我有兩個問題。首先，D-B06於三月初步竣工。數據是內部的嗎？這是否支撐了你的信心？其次，為什麼在提供口服 GLP-1 和口服 PCSK9 數據方面似乎出現了很長的延遲？我可以想到四個可能的原因。

One, there's a lack of appropriate venues. Two, AstraZeneca is strategizing on next steps on how to approach the market and wants to figure this out first. Three, there's some issue with the molecules or data that you're working through, perhaps it is underwhelming. Or four, we're just being too optimistic on how long this all takes. So any thoughts would be appreciated.

一是缺乏合適的場地。第二，阿斯特捷利康正在製定下一步如何進入市場的策略，並希望先解決這個問題。第三，你正在研究的分子或數據存在一些問題，也許沒有給人留下深刻的印象。或者第四，我們對這一切需要多長時間過於樂觀。因此，任何想法將不勝感激。

Thanks, Steve. So let me just address the last one quickly and then we could talk about D-B06. And you forgot one option, which is our policy. And our policy is to present data at medical congresses. And that's what we have decided to do, we stick to this. But maybe your second option is also part of it. For sure, we are, in the meantime, strategizing what we're going to do with our portfolio and how we develop this product.

謝謝，史蒂夫。所以讓我快速解決最後一個問題，然後我們可以討論 D-B06。您忘記了一個選項，那就是我們的政策。我們的政策是在醫學大會上展示數據。這就是我們決定要做的，我們堅持下去。但也許你的第二個選擇也是其中的一部分。當然，與此同時，我們正在製定我們將如何處理我們的產品組合以及如何開發該產品的策略。

But really, the driving force is simply we debated it internally because you raised a good point. But we concluded we didn't want to do -- to come up with an exception here. And so you'll have to wait for the next potential option is a medical congress. We are, by the way, have said, and I think I can confirm, we're starting Phase II this year. So we are very much on track, and we will not be preparing Phase II if we were not confident with the oral GLP-1. D-B06, Susan, do you want to cover that?

但實際上，驅動力只是我們內部辯論，因為你提出了一個很好的觀點。但我們得出的結論是，我們不想在這裡提出一個例外。所以你必須等待下一個可能的選擇是醫學大會。順便說一句，我們已經說過，而且我想我可以確認，我們今年將開始第二階段。所以我們已經步入正軌，如果我們對口服 GLP-1 沒有信心，我們就不會準備第二階段。 D-B06，蘇珊，你想報這個嗎？

Yes, sure. So DESTINY-Breast06 is obviously a setting earlier than DESTINY-Breast04. It includes the IHC 1+ and 2+ as well as a group of the ultra-low group. And the confidence in DESTINY-Breast06 is really built from the DESTINY-Breast04 dataset, which we obviously presented some time ago. So we are looking forward to the data. We said it's first half of this year. So hopefully, you don't have to wait too long for getting those data. And we're eager to share them with you.

是的，當然。所以DESTINY-Breast06很明顯是早於DESTINY-Breast04的設定。它包括 IHC 1+ 和 2+ 以及一組超低組。對 DESTINY-Breast06 的信心實際上是根據 DESTINY-Breast04 資料集建立的，顯然我們不久前已經展示過該資料集。所以我們對數據充滿期待。我們說的是今年上半年。因此，希望您不必等待太久即可取得這些數據。我們渴望與您分享它們。

Again, just as a reminder, the primary endpoint is PFS in the HER2-low group, so the IHC 1+ and 2+. And then there will be descriptive analysis of the HER2 ultra-low patient population as well. And as a reminder further, even though these patients are below the 1+ category, they still have a higher number of HER2 receptors on the cell surface than normal epithelium. So just to put numbers on that, normal epithelium for HER2 is about 20,000 receptors per cell, at the 1+ to 2+, it ranges between 100,000 and 200,000. So in that ultra-low group, you've got somewhere between 20,000 and 100,000 receptors per cell.

再次提醒一下，主要終點是 HER2-low 組的 PFS，因此 IHC 1+ 和 2+。然後也將對 HER2 超低患者族群進行描述性分析。進一步提醒一下，即使這些患者低於 1+ 類別，他們的細胞表面上的 HER2 受體數量仍然高於正常上皮。簡單來說，正常上皮細胞每個細胞大約有 20,000 個 HER2 受體，在 1+ 到 2+ 範圍內，範圍在 100,000 到 200,000 之間。因此，在那個超低組中，每個細胞有 20,000 到 100,000 個受體。

So you can see that there's probably a significant proportion of that group that will have a higher expression level of HER2 on the cell surface than normal epithelium would. And that's one of the reasons why we think there's a potential to go beyond the 1+ group into that ultra-low group and see benefit over the current standard of care chemotherapies.

因此您可以看到，該組中可能有很大一部分細胞表面的 HER2 表達水平高於正常上皮細胞。這就是為什麼我們認為有可能超越 1+ 組進入超低組並看到比目前標準護理化療有好處的原因之一。

Thanks, Susan. Next question is from Simon Baker at Redburn.

謝謝，蘇珊。下一個問題來自 Redburn 的 Simon Baker。

Two, if I may, please. Firstly, going back to Farxiga, I just wonder if you could talk us through the rationale for the timing of the authorized generic now. I may be missing something, but the comp of matter patent goes in October '25. So just thoughts there would be helpful. Alongside, also the FDA issuing a request for pediatric studies in March 2019, that hasn't yet been reflected in the Orange Book. So I just wondered, what's the status of that was.

兩個，如果可以的話，請。首先，回到 Farxiga，我只是想知道您是否可以向我們介紹現在授權仿製藥的時間表的理由。我可能遺漏了一些東西，但該複合材料專利於 25 年 10 月發布。所以只是想法會有幫助。除此之外，FDA 也於 2019 年 3 月發布了兒科研究請求，但尚未反映在橙皮書中。所以我只是想知道那是什麼狀態。

And then secondly, on TROPION-Lung10, you've moved forward with one of the combinations, which is in the TROPION-Lung04 study, obviously, on high confidence. I just wondered where that -- where your confidence rests with the combination with volrustomig and sabestomig?

其次，在 TROPION-Lung10 上，您已經推進了其中一種組合，顯然，該組合在 TROPION-Lung04 研究中具有高置信度。我只是想知道您對 volrustomig 和 sabestomig 組合的信心在哪裡？

Thank you, Simon. So Ruud, in the past, you were complaining, not enough questions to BioPharma, you're now going to complain, too many questions.

謝謝你，西蒙。所以路德，過去你抱怨，向生物製藥公司提出的問題不夠多，現在你要抱怨，問題太多了。

No, it could be less. But no, it's a great question, Simon. So why now? It's relatively straightforward. First of all, we have a huge opportunity still in CKD and heart failure. And it is clear from all the analytics we have done that a lower-cost option for some of those patients are very important in order to capture even more volume. The second one is also true that, to a certain extent, it also mitigates the impact of a potential MCAP, so the inflation penalty in the United States as well. So those two factors were important regarding the timing.

不，可能會更少。但不，這是一個很好的問題，西蒙。那為什麼現在呢？這相對簡單。首先，我們在 CKD 和心臟衰竭方面仍然有巨大的機會。從我們所做的所有分析中可以清楚地看出，對於其中一些患者來說，為了獲得更多的治療量，低成本的選擇非常重要。第二個也是如此，在某種程度上，它也減輕了潛在的 MCAP 的影響，因此也減輕了美國的通膨懲罰。因此，這兩個因素對於時間安排非常重要。

Regarding the pediatric indication, it's not yet in the Orange Book so that's a very good observation. But equally, we feel comfortable that the FDA will grant us the pediatric indication. And hence, our base assumption is still that the patent will stay in place till April 2026, which we have signaled multiple times.

關於兒科適應症，在橙皮書上還沒有，所以這是一個非常好的觀察。但同樣，我們對 FDA 授予我們兒科適應症感到放心。因此，我們的基本假設仍然是該專利將保留到 2026 年 4 月，我們已經多次表示這一點。

Thanks, Ruud. Susan, do you want to cover the second question?

謝謝，路德。蘇珊，你想回答第二個問題嗎？

Yes. So the TROPION-Lung10 study, as I mentioned before, is a combination with rilvegostomig and dato. And it's in a patient population that's greater than 50%. As we said before, what we see in terms of the evolution of the IO checkpoint inhibitor landscape is a segmentation. And our two bispecifics, we see the rilvegostomig PD-1, TIGIT as being focused on the IO-sensitive or highly expressing PD-L1 part of the population. And that's in line with what you see in terms of the patient population in TROPION-Lung10.

是的。因此，正如我之前提到的，TROPION-Lung10 研究是 rilvegostomig 和 dato 的組合。而且它在患者群體中的比例超過 50%。正如我們之前所說，我們所看到的 IO 檢查點抑制劑格局的演變是一個細分。我們的兩種雙特異性藥物，我們認為 rilvegostomig PD-1、TIGIT 專注於 IO 敏感或高度表達 PD-L1 的族群。這與您在 TROPION-Lung10 的患者群體中看到的情況一致。

Volrustomig, we're focusing that on the tumor types, where CTLA-4 sensitivity has been demonstrated and can add extra efficacy. Obviously, with volrustomig, it is designed to be better tolerated than the combination of CTLA-4 and PD-1 separately because it only binds CTLA-4 in the presence of PD-1. And we have shown an improved safety profile. But it still does have more side effects than you'd get with a PD-1 agent on its own or with rilvegostomig. So we will select that drug where it will make the biggest difference. And you'll see that as you see the evolution of the eVOLVE studies with volrustomig.

Volrustomig，我們將重點放在腫瘤類型上，CTLA-4 的敏感性已得到證實，並且可以增加額外的療效。顯然，volrustomig 的設計比單獨使用 CTLA-4 和 PD-1 的組合具有更好的耐受性，因為它僅在 PD-1 存在的情況下結合 CTLA-4。我們已經展示了改進的安全狀況。但與單獨使用 PD-1 藥物或合併 rilvegostomig 相比，它的副作用仍然較多。因此，我們將選擇能產生最大影響的藥物。當您看到 volrustomig 的 eVOLVE 研究的演變時，您就會看到這一點。

Thanks, Susan. Next question is from Andrew Berens at Leerink.

謝謝，蘇珊。下一個問題來自 Leerink 的 Andrew Berens。

Congrats on a strong quarter. Kind of big-picture question on the AKT class, given the results of Truqap, just wondering how you see it integrating the evolving paradigms. It's obviously incredibly dynamic, and specifically would like know how you guys see the AKT class integrating with CDK2 agents, CDK4 selective drugs, the oral SERDs, degraders and also the ADCs that are starting to spread their wings into a number of these areas.

恭喜季度表現強勁。考慮到 Truqap 的結果，這是關於 AKT 類別的宏觀問題，只是想知道您如何看待它整合不斷發展的範式。這顯然是令人難以置信的動態，特別想知道你們如何看待 AKT 類與 CDK2 藥物、CDK4 選擇性藥物、口服 SERD、降解劑以及開始擴展到其中一些領域的 ADC 的整合。

Okay, Andrew, thank you. Thank you for asking one question, actually. Susan, over to you.

好的，安德魯，謝謝你。事實上，謝謝你問一個問題。蘇珊，交給你了。

Yes. So thanks for the question. So AKT is obviously part of the PI3 kinase/AKT pathway, which is the most commonly mutated or aberrant pathway in cancer. So we think this is a very important mechanism. And we are looking at combinations of capivasertib with our camizestrant, our oral SERD drug that's already in multiple Phase III trials as well. So I think there's potential for it to be further expanded beyond the current set of trials that we've already got in development. And I do think there are data that it can be a potential combination agent with a number of the other things that you raised.

是的。謝謝你的提問。因此，AKT 顯然是 PI3 激酶/AKT 路徑的一部分，而 PI3 激酶/AKT 路徑是癌症中最常見的突變或異常路徑。所以我們認為這是一個非常重要的機制。我們正在研究 capivasertib 與我們的 camizestrant 的組合，我們的口服 SERD 藥物也已經處於多個 III 期試驗中。因此，我認為它有可能進一步擴展到我們目前已經開發的一系列試驗之外。我確實認為有數據表明它可以與您提出的許多其他東西一起成為潛在的組合劑。

We do have a CDK2 inhibitor, a highly selective CDK2 inhibitor, which we profiled at the AACR meeting that was in San Diego earlier this month. We think that's a very exciting molecule that will address the resistance mechanisms to the CDK4/6 inhibitors. And so I do think that this cast of agents can be combined with the emerging, both new endocrine backbone agents and the newer versions of things that address the CDK4 mechanism and the resistance to CDK4, which typically is represented by sensitivity to CDK2 inhibition.

我們確實有一種 CDK2 抑制劑，一種高度選擇性的 CDK2 抑制劑，我們在本月早些時候於聖地亞哥舉行的 AACR 會議上對其進行了介紹。我們認為這是一個非常令人興奮的分子，它將解決 CDK4/6 抑制劑的抗藥性機制。因此，我確實認為這一系列藥物可以與新興的新內分泌骨幹藥物和解決 CDK4 機制和 CDK4 抗性（通常表現為對 CDK2 抑制的敏感性）的新版本藥物相結合。

Just maybe to also build on to Susan's answer, and I think what's important and great about this is we're talking about leadership in breast cancer. And as part of that leadership in breast cancer, we're really looking to build and improve upon the two existing pillars in the treatment of metastatic disease and then adding a third. And the existing treatments and existing pillars are ET, plus or minus, CDK4/6 and then obviously chemotherapy. I think what's important about the AKT class is it gives an opportunity for patients to continue to stay on ET-based therapies, which has a lot of benefits associated with it.

也許也是以蘇珊的答案為基礎，我認為最重要和偉大的是我們正在談論乳癌領域的領導。作為乳癌領域領導地位的一部分，我們確實希望在轉移性疾病治療方面建立和改善現有的兩個支柱，然後增加第三個支柱。現有的治療方法和現有的支柱是 ET，加或減，CDK4/6，然後顯然是化療。我認為 AKT 類別的重要之處在於它為患者提供了繼續接受基於 ET 的治療的機會，這有很多好處。

We also know though that at some point, ET therapies are no longer effective and that it's a time to start to switch towards chemotherapy. And within that, that's where the ADCs now create a third new pillar that sits in between classical chemotherapy and ET-based approaches. We hope that D-B06 will provide even a further therapy option that sits within this. But you start to see the opportunity to begin to offer to physicians more options for how they can think about treating their patients as the disease progresses. And we've got best-in-class therapies to go into each of those pillars and then gives us an opportunity to look at combinations down the road.

我們也知道，在某些時候，ET 療法不再有效，是時候開始轉向化療了。其中，ADC 現在創建了第三個新支柱，位於經典化療和基於 ET 的方法之間。我們希望 D-B06 能夠提供進一步的治療選擇。但你開始看到機會開始為醫生提供更多選擇，讓他們隨著疾病的進展考慮如何治療患者。我們已經為每個支柱提供了一流的療法，然後讓我們有機會研究未來的組合。

Thanks, Dave. Actually, this discussion gives me a chance to go back to, I think, the question Richard was asking earlier about the pipeline. I mentioned combinations. But also this pipeline enables us to actually shape the treatment algorithm, as Dave was suggesting a minute ago, in breast cancer or lung cancer. And it also enables us to better partner with lung cancer oncologists or breast cancer oncologists and really truly be part of the way breast or lung cancer or other cancers are treated.

謝謝，戴夫。事實上，我認為這次討論讓我有機會回到理查德早些時候提出的有關管道的問題。我提到了組合。而且這個管道也使我們能夠真正塑造乳癌或肺癌的治療演算法，正如戴夫在一分鐘前所建議的那樣。它還使我們能夠更好地與肺癌腫瘤學家或乳癌腫瘤學家合作，並真正成為乳癌或肺癌或其他癌症治療方式的一部分。

And it's true for cardiologists, not only managing cardiovascular risk, but also if you look at amyloidosis, we have 2220, which is an amyloid depleter. And we also have eplontersen. So again, all of those things will give us a great chance to not only work with key physicians but also leverage our portfolio to shape treatment algorithms and look at combinations.

對於心臟科醫生來說也是如此，不僅要管理心血管風險，而且如果你觀察澱粉樣變性，我們有 2220，它是一種澱粉樣蛋白消耗劑。我們還有eplontersen。因此，所有這些事情都將為我們提供一個很好的機會，不僅可以與主要醫生合作，還可以利用我們的產品組合來建立治療演算法並研究組合。

Emily Field of Barclays.

巴克萊銀行的艾米麗·菲爾德。

Just two on respiratory. A lot of excitement about the tezepelumab COPD data to be presented at ATS. Given what we've seen so far, is it your expectation that this would be taken in late-stage development in a broader eosinophil population, i.e., over 150s and over 300s?

只有兩個呼吸系統。 ATS 上公佈的 tezepelumab COPD 數據令人興奮不已。鑑於我們迄今為止所看到的情況，您是否期望在更廣泛的嗜酸性粒細胞群體（即超過 150 歲和超過 300 歲）的後期開發中採取這種方法？

And then on the back of that, similar to the obesity question that was asked earlier, you have so many assets in late-stage development in COPD. Maybe asking from our side, what should we be focusing on in terms of just all of the late-stage COPD programs that you have?

在此基礎上，與先前提出的肥胖問題類似，慢性阻塞性肺病的後期發展有許多優點。也許從我們這邊問，對於你們擁有的所有晚期慢性阻塞性肺病項目，我們應該關注什麼？

Sure. Thanks so much for the question. So I'll start with your first one, which was about tezepelumab and our Phase II COURSE study and then I will speak more broadly about the COPD portfolio. So you touched on teze and our recent Phase II trial completion. And we look forward to presenting those data at ATS in the very near future. As I'm sure you know, teze is a monoclonal antibody directed against TSLP. It is the only biologic approved for severe asthma with no phenotype. And we see tremendous potential for this molecule in COPD.

當然。非常感謝您的提問。因此，我將從您的第一個開始，這是關於 tezepelumab 和我們的 II 期課程研究，然後我將更廣泛地談論 COPD 產品組合。您談到了 teze 和我們最近完成的第二階段試驗。我們期待在不久的將來在 ATS 上展示這些數據。我相信您知道，teze 是一種針對 TSLP 的單株抗體。它是唯一被批准用於治療無表型嚴重氣喘的生物製劑。我們看到了這種分子在慢性阻塞性肺病中的巨大潛力。

The COURSE Phase II study was specifically designed to look at a broader population of patients. So it included patients irrespective of inflammatory drivers, eosinophil levels, emphysema, chronic bronchitis and smoking status while other trials were more limited. And this included a prespecified subgroup analysis in populations with different eosinophilic levels, so including below 150, above 150 and above 300. We will present the data that we fully analyzed at the upcoming ATS meeting. But I will only venture to say that we are excited about the possibility of teze in a broader population.

COURSE II 期研究是專門為觀察更廣泛的患者群體而設計的。因此，它納入的患者與發炎驅動因素、嗜酸性粒細胞水平、肺氣腫、慢性支氣管炎和吸煙狀況無關，而其他試驗則更為有限。這包括對不同嗜酸性粒細胞水平的人群進行預先指定的亞組分析，包括低於 150、高於 150 和高於 300。但我只想大膽地說，我們對特茲在更廣泛人群中的可能性感到興奮。

It is worth noting that other molecules in this class are playing in the high eosinophilic levels, at more than 300 eosinophils per microliter. And that's only about 35% of the population that's eligible for biologics. But those above 150 eosinophils per microliter are about 65% of the biologics-eligible population in COPD. So we think that's a really important differentiator for this molecule. Now you also mentioned -- I think you also asked us about our plans to go forward. Together with our collaborators at Amgen, we are actively planning the next stage of development.

值得注意的是，此類中的其他分子在高嗜酸性粒細胞水平上發揮作用，每微升超過 300 個嗜酸性粒細胞。而只有約 35% 的人口有資格獲得生物製劑。但每微升嗜酸性球超過 150 的人約佔 COPD 適合使用生物製劑的人的 65%。所以我們認為這是該分子的一個非常重要的區別因素。現在你也提到──我想你也問了我們未來的計畫。我們正在與安進的合作者一起積極規劃下一階段的發展。

You asked about our overall portfolio in COPD. And I think it's worth mentioning here that COPD is a very heterogeneous disease with multiple drivers. And to that end, we think that there are multiple mechanisms that may have substantial clinical benefit. So we are testing multiple mechanisms. And we are testing them in populations that allow us to differentiate them from each other. Tozorakimab, as we have previously described, is a differentiated IL-33 monoclonal antibody because it can bind and block both ST2 and RAGE/EGFR signaling.

您詢問了我們在慢性阻塞性肺病方面的整體產品組合。我認為這裡值得一提的是，慢性阻塞性肺病是一種異質性很強的疾病，有許多驅動因素。為此，我們認為有多種機制可能具有實質的臨床益處。所以我們正在測試多種機制。我們正在人群中對它們進行測試，以便我們能夠將它們彼此區分開來。正如我們之前所描述的，Tozorakimab 是一種差異化的 IL-33 單株抗體，因為它可以結合併阻斷 ST2 和 RAGE/EGFR 訊號傳導。

We think that's really important in this disease. Because it not only blocks the inflammatory pathways, but it can also block mucus production and epithelial remodeling through RAGE/EGFR. So we view that as a differentiated mechanism, which we think may also have very broad utility in the COPD population. So early days, we are reading into our Phase II data and thinking about our Phase III plans going forward. But I think that we have the potential to be really paradigm-shifting for people living with COPD.

我們認為這對這種疾病非常重要。因為它不僅阻斷發炎途徑，還可以透過RAGE/EGFR阻斷黏液產生和上皮重塑。因此，我們認為這是一種差異化機制，我們認為它在慢性阻塞性肺病人群中也可能具有非常廣泛的用途。所以早期，我們正在研究第二階段的數據並思考我們未來的第三階段計劃。但我認為我們有潛力為慢性阻塞性肺病患者帶來真正的典範轉移。

Thank you, Sharon. Luisa Hector at Berenberg.

謝謝你，莎倫。貝倫貝格的路易莎·赫克托。

Perhaps I could touch on capital allocation. So your high burden of deal-related payments will start to ease at the end of this year so that improves your cash flow outlook. So will this lead to a change in the nature of deals which you can do? And perhaps you could remind us of your dividend policy, given a slightly unusual announcement of the 2024 dividend recently.

也許我可以談談資本配置。因此，您的交易相關付款的沉重負擔將在今年年底開始減輕，從而改善您的現金流前景。那麼這會導致您可以進行的交易性質改變嗎？鑑於最近公佈的 2024 年股息有點不尋常，也許您可以提醒我們您的股息政策。

Thanks, Luisa. Aradhana, your favorite question.

謝謝，路易莎。 Aradhana，你最喜歡的問題。

Thank you, Luisa. So our capital allocation priorities remain unchanged. As you've seen, we've been very active on the BD front. But we also now sort of need to create value actually from the acquisitions and the partnership transactions we've done. So we need to focus on execution of those transactions.

謝謝你，路易莎。因此，我們的資本配置重點保持不變。正如您所看到的，我們在 BD 方面一直非常活躍。但我們現在還需要從我們所做的收購和合作夥伴交易中實際創造價值。因此，我們需要專注於這些交易的執行。

We did announce a 7% dividend increase in line with our progressive dividend policy. But also recall that we did not increase dividends in 2022. And so the Board takes a decision on when and how they can increase dividends based on our overall capital allocation priorities. But the capital allocation remains unchanged.

我們確實宣布根據我們的漸進式股利政策增加 7% 的股利。但也要記住，我們沒有在 2022 年增加股利。但資本配置維持不變。

Thank you, Aradhana. And so thank you very much for all your great questions. I think it is time for us to respect your time and close this call. Again, thank you so much for all your great questions and your interest in AstraZeneca, and have a good rest of the day.

謝謝你，阿拉達納。非常感謝您提出的所有好問題。我認為現在是我們尊重您的時間並結束本次通話的時候了。再次非常感謝您提出的所有好問題以及您對阿斯特捷利康的興趣，並祝您今天休息愉快。