AstraZeneca PLC (AZN) 2022 Q2 法說會逐字稿

Good morning to those from the U.K. and U.S., good afternoon to those in Central Europe, and good evening to those listening in Asia. Welcome, ladies and gentlemen, to AstraZeneca's Half Year 2022 Results Conference Call and Webcast for investors and analysts.

早上好，來自英國和美國的人們，下午好，來自中歐的人們，晚上好，來自亞洲的聽眾。女士們，先生們，歡迎參加阿斯利康為投資者和分析師舉行的 2022 年半年度業績電話會議和網絡直播。

Before I hand over to AstraZeneca, I'd like to read the Safe Harbor statement. The company intends to utilize the Safe Harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements with respect to the operations and financial performance of AstraZeneca. Although we believe our expectations are based on reasonable assumptions, by their very nature, forward-looking statements involve risks and uncertainties and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these forward-looking statements. Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements.

在我交給阿斯利康之前，我想閱讀安全港聲明。公司打算利用 1995 年美國私人證券訴訟改革法案的安全港條款。本次電話會議的參與者可能會就阿斯利康的運營和財務業績做出前瞻性陳述。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，並可能受到可能導致實際結果與這些前瞻性陳述所表達或暗示的結果存在重大差異的因素的影響。在本次電話會議上所做的任何前瞻性陳述都反映了本次電話會議時可獲得的知識和信息。公司不承擔更新前瞻性陳述的義務。

Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this conference call and webcast. There will be an opportunity to ask questions after today's presentations. (Operator Instructions)

還請仔細閱讀本次電話會議和網絡廣播隨附的幻燈片中的前瞻性聲明免責聲明。今天的演講結束後將有機會提問。 （操作員說明）

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

有了這個，我現在將把你交給阿斯利康。

Thank you, operator, and welcome, everyone. I'm Andy Barnett , Head of Investor Relations at AstraZeneca, and I'm pleased to welcome you to AstraZeneca's First Half 2022 Conference Call. All materials presented today are available on our website.

謝謝運營商，歡迎大家。我是阿斯利康（AstraZeneca）投資者關係主管安迪·巴尼特（Andy Barnett），很高興歡迎您參加阿斯利康（AstraZeneca）2022 年上半年的電話會議。今天介紹的所有材料都可以在我們的網站上找到。

Slide 2 has our usual Safe Harbor statement. We will be making comments on our performance using constant exchange rates, or CER, core financial numbers and other non-GAAP measures. A non-GAAP to GAAP reconciliation is contained within the results announcement. Numbers used are in millions of U.S. dollars and for the first half, unless otherwise stated.

幻燈片 2 有我們通常的安全港聲明。我們將使用恆定匯率或 CER、核心財務數據和其他非公認會計原則衡量指標對我們的業績發表評論。結果公告中包含非公認會計原則與公認會計原則的對賬。除非另有說明，否則使用的數字以百萬美元為單位，為上半年。

Please advance to Slide 3. This slide shows our agenda for today's call, and in a moment, I'll hand over to our CEO, Pascal Soriot, to begin. Following our prepared remarks, we will open the line for questions. (Operator Instructions)

請轉到幻燈片 3。這張幻燈片顯示了我們今天電話會議的議程，稍後，我將由我們的首席執行官 Pascal Soriot 開始發言。在我們準備好的評論之後，我們將打開提問線。 （操作員說明）

With that, please advance to Slide 4, and I'll hand over to Pascal.

有了這個，請轉到幻燈片 4，我將交給帕斯卡。

Thank you, Andy. Hello, everyone, and welcome to this half year call. So if we move to Slide 5, please. We continue to deliver for the first half of 2022 both in terms of commercial performance as well as moving our pipeline forward. Total revenue increased 48% versus prior year to $22.2 billion, and core EPS increased by 44% to $3.61.

謝謝你，安迪。大家好，歡迎來到這個半年的電話會議。所以，如果我們轉到幻燈片 5，請。我們將在 2022 年上半年繼續交付，無論是在商業表現方面，還是在推進我們的管道方面。總收入較上年增長 48% 至 222 億美元，核心每股收益增長 44% 至 3.61 美元。

Given the strength of our underlying business as well as increased demand for our COVID-19 medicines, which delivered $2.5 billion of revenue in the first half, we have updated our revenue guidance for the year. We now expect revenue growth for the full year to increase at a low 20s percentage.

鑑於我們基礎業務的實力以及對我們上半年收入 25 億美元的 COVID-19藥物的需求增加，我們更新了今年的收入指引。我們現在預計全年的收入增長將在 20% 的低位增長。

Guidance on EPS remained unchanged, and we continue to expect a mid to high 20 percentage increase as we continue to invest in our pipeline. We have also confirmed an interim dividend of $0.93, reflecting the Board's intention to increase the dividend to $2.90 for the full year of 2022.

每股收益的指導保持不變，隨著我們繼續投資我們的管道，我們繼續預計會出現 20% 的中高增長。我們還確認了 0.93 美元的中期股息，反映出董事會打算將 2022 年全年的股息增加到 2.90 美元。

Looking across our business, we delivered revenue growth from all business areas, reflecting not only the breadth of our portfolio but also the depth in each of our respective business areas. In the first half of the year, we reported several important late-stage data readouts, including Farxiga in heart failure, Ultomiris in NMO and Imfinzi in non-small cell lung cancer, and we received significant approvals, enabling commercial launches.

縱觀我們的業務，我們在所有業務領域都實現了收入增長，這不僅反映了我們投資組合的廣度，也反映了我們各自業務領域的深度。今年上半年，我們報告了幾個重要的後期數據讀數，包括心力衰竭的 Farxiga、NMO 的 Ultomiris 和非小細胞肺癌的 Imfinzi，我們獲得了重要的批准，實現了商業發布。

Please move to Slide 6. In order to maintain our ambition for long-term industry-leading growth, we will need to maximize our launches and continue to invest in our great pipeline and our research technologies.

請移至幻燈片 6。為了保持我們對長期行業領先增長的雄心，我們將需要最大限度地提高我們的發布並繼續投資於我們的優秀管道和我們的研究技術。

First, our pipeline successes have been driven -- have driven increased need to resource commercial launches. With competition increasing in many markets, investing smartly to optimize our launches has never been more important. Spend on market development for medicines like Evusheld is also important if we are to unlock the full potential of this medicine.

首先，我們的管道成功得到了推動——推動了對資源商業發射的需求增加。隨著許多市場競爭的加劇，明智地投資以優化我們的發布從未像現在這樣重要。如果我們要釋放這種藥物的全部潛力，在 Evusheld 等藥物的市場開發上的支出也很重要。

Based on emerging data, we need to act fast and invest to win with high potential pipeline opportunities. And we have several medicines as we see -- as you see here on the second column in this chart, we have several medicines where recent data has pointed to the potential for major clinical advances and sizable commercial opportunities. So we last -- we have listed here, as you can see on this chart, the successes we've experienced in the last few months, but also in the middle, the priority assets that we are fully resources for maximum potential.

基於新出現的數據，我們需要快速行動並進行投資，以贏得潛在的潛在管道機會。正如我們所看到的，我們有幾種藥物——正如你在這張圖表的第二列中看到的那樣，我們有幾種藥物，最近的數據表明它們具有重大臨床進展和巨大商業機會的潛力。所以我們最後 - 正如你在這張圖表中看到的那樣，我們在這裡列出了我們在過去幾個月中取得的成功，但也在中間，我們是充分發揮最大潛力的資源的優先資產。

Thirdly, there is a continued need to invest in early discovery research and new technologies to accelerate the rate of pipeline growth, and you can see here a number of those technologies. And in particular in [rare disease] we've made tremendous progress in the last 2 years, and Susan will highlight a little bit more examples of this.

第三，需要持續投資於早期發現研究和新技術以加快管道增長速度，您可以在這裡看到其中的一些技術。特別是在[罕見疾病]方面，我們在過去 2 年中取得了巨大進展，Susan 將重點介紹更多這方面的例子。

In addition to our goal of reducing SG&A spend as a percentage of sales over time, in R&D, we have set bold internal targets to drive efficiencies for the use of digital solutions. For example, we have invested in remote data collection for many of our global trials as well as the use of real-world evidence and data science to optimize trial design to improve the success rate. This improvement will make our trials more efficient, more accessible for patients and reduce our indirect impact on the climate.

除了隨著時間的推移降低 SG&A 支出佔銷售額的百分比之外，在研發方面，我們還設定了大膽的內部目標，以提高數字解決方案的使用效率。例如，我們為我們的許多全球試驗投資了遠程數據收集，以及使用真實世界的證據和數據科學來優化試驗設計以提高成功率。這一改進將使我們的試驗更加高效，患者更容易獲得，並減少我們對氣候的間接影響。

We've also worked to internalize clinical operations to drive further efficiencies.

我們還致力於將臨床操作內部化，以進一步提高效率。

A rigorous approach to portfolio prioritization is also being applied, which is enabling the direct number of investment being the most promising medicines and the discontinuation of development for others, such as the 3 that are mentioned here. These decisions are difficult, but given the breadth of our portfolio, are increasingly important. So as you can see here, we are not only investing but we're also driving productivity improvement very aggressively.

還採用了嚴格的組合優先級方法，這使得直接投資成為最有前途的藥物，並停止其他藥物的開發，例如這裡提到的 3 種。這些決定很困難，但考慮到我們投資組合的廣度，它們變得越來越重要。因此，正如您在此處看到的，我們不僅在投資，而且還在非常積極地推動生產力的提高。

Together, these investments will help us deliver our ambition for low double-digit CAGR through 2025 and industry-leading growth thereafter. We want to remain a fast-growing company beyond 2025, and we are confident we have in our hands what it takes to be a growing company until 2030, and hopefully, even beyond 2030.

總之，這些投資將幫助我們實現到 2025 年實現低兩位數複合年增長率以及此後實現行業領先增長的雄心。我們希望在 2025 年之後仍然是一家快速發展的公司，我們有信心在 2030 年之前，甚至在 2030 年之後，我們都掌握著成為一家成長型公司所需的條件。

At the same time, we remain committed to increasing operating leverage. And so despite the need to invest in new launches, our pipeline and technologies, we remain focused on improving operating margin. We're confident that this combination of industry-leading growth and operating leverage will drive shareholder value.

與此同時，我們仍然致力於提高經營槓桿。因此，儘管需要對新產品、我們的管道和技術進行投資，但我們仍然專注於提高營業利潤率。我們相信，行業領先的增長和運營槓桿的結合將推動股東價值。

So please move to Slide 7. We look forward to a productive back half of the year, and we have several Phase III readouts, including the EMERALD-1 trial of Imfinzi in locoregional liver cancer. The first Phase III readout for capivasertib in HR+ HER2 negative breast cancer and MESSINA trial of Fasenra in EoE.

所以請轉到幻燈片 7。我們期待今年下半年富有成效，我們有幾個 III 期讀數，包括 Imfinzi 在局部區域肝癌中的 EMERALD-1 試驗。 capivasertib 在 HR + HER2 陰性乳腺癌中的第一個 III 期讀數和 Fasenra 在 EoE 中的 MESSINA 試驗。

And in 2023, we expect more than 20 Phase III readouts. The next couple of years are going to be extremely rich in clinical readouts. We are well positioned to deliver industry-leading growth through 2025 and beyond, as I said, and I look forward to sharing more exciting news as we -- as our pipeline progresses.

到 2023 年，我們預計會有超過 20 個 III 期讀數。未來幾年的臨床讀數將非常豐富。正如我所說，我們有能力在 2025 年及以後實現行業領先的增長，我期待隨著我們的管道進展，分享更多令人興奮的消息。

Please advance to the next slide, and I will now hand over to Aradhana to walk you through our financials in the first half of the year.

請前進到下一張幻燈片，我現在將交給 Aradhana，帶您了解我們上半年的財務狀況。

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

謝謝你，帕斯卡，大家下午好。像往常一樣，我將從我們報告的損益開始。

Please turn to Slide 9. As Pascal has already highlighted, total revenue grew by 48% in the first half, benefiting from a full quarter of Alexion sales and higher revenues from COVID-19 medicines. Our collaboration revenue increased to $551 million in the half, partly driven by increase in HER2 sales. As a reminder, Daiichi Sankyo books in HER2 product sales in most Western markets while we record our share of gross profits in those regions as collaboration revenue.

請轉到幻燈片 9。正如 Pascal 已經強調的那樣，上半年總收入增長了 48%，這得益於 Alexion 整個季度的銷售和 COVID-19藥物的更高收入。上半年，我們的合作收入增至 5.51 億美元，部分原因是 HER2 銷售額的增長。提醒一下，第一三共記入大多數西方市場的 HER2 產品銷售，而我們將這些地區的毛利潤份額記錄為合作收入。

We record our share of the R&D and sales and marketing costs in our P&L. We will, however, book product sales in China upon launch. Our reported gross margin continues to be adversely impacted by the Alexion fair value uplift, which we anticipate to continue for another 6 months or so until the inventory is sold.

我們在損益表中記錄我們在研發、銷售和營銷成本中所佔的份額。但是，我們將在推出產品時預訂在中國的產品銷售。我們報告的毛利率繼續受到 Alexion 公允價值提升的不利影響，我們預計這將持續另外 6 個月左右，直到庫存售出。

Please turn to Slide 10. Turning to the core P&L, our core gross margin increased by 6 percentage points in the first half to 81.1%, with the second quarter benefiting from the phasing of cost recognition associated with the fulfillment of Vaxzevria contracts as well as favorable currency movements.

請轉到幻燈片 10。關於核心損益表，我們的核心毛利率在上半年增長 6 個百分點至 81.1%，第二季度受益於與 Vaxzevria 合同的履行相關的成本確認分階段以及有利的貨幣走勢。

While quarterly fluctuations of the growth margin may continue, we still expect the ex-COVID-19 group core gross margins this year to be relatively stable compared to pre-COVID levels.

儘管增長利潤率的季度波動可能會繼續，但我們仍預計今年前 COVID-19 集團核心毛利率與 COVID 之前的水平相比相對穩定。

Our core operating expenses increased by 33% in the first half, driven by the addition of Alexion, which given timing of the consolidation had no contribution in the first half of 2021. To echo Pascal's comments, the increase in cost also reflects continued investments in R&D where several positive readouts in the last several months have ungated additional trials. We also recognized a one-off charge of $89 million in the second quarter relating to a discontinued project.

由於 Alexion 的加入，我們上半年的核心運營費用增長了 33%，鑑於合併的時間安排在 2021 年上半年沒有任何貢獻。與 Pascal 的評論相呼應，成本的增加也反映了持續投資於過去幾個月的幾個積極讀數的研發已經取消了額外的試驗。我們還在第二季度確認了與已終止項目有關的 8900 萬美元的一次性費用。

The pace of approvals following our pipeline success, necessitated investment in new launches, resulting in a 29% increase in SG&A costs in the first half. But again, compared to a 2021 number which did not include Alexion. SG&A costs during the period also reflect increased investment behind the launch of Evusheld, where we're focused on driving end-market demand. We continue to work to expand capacity following the recent dosing update.

我們管道成功後的審批速度需要對新產品進行投資，導致上半年 SG&A 成本增加了 29%。但同樣，與不包括 Alexion 的 2021 年數字相比。在此期間的 SG&A 成本也反映了 Evusheld 推出背後的投資增加，我們專注於推動終端市場需求。在最近的劑量更新之後，我們繼續努力擴大產能。

Our core operating margin was 33.1% in the first half and 31.2% in the second quarter, benefiting from higher gross margins. On the net income line, we benefited from a lower tax rate in the second quarter, which was driven by favorable adjustments when we filed our 2021 tax return in major jurisdictions. Variations in tax rate between the quarters are expected to continue, but we still anticipate a core tax rate of 18% to 22% for the full year. Second quarter core EPS of $1.72 in the second quarter represents 89% growth.

得益於較高的毛利率，我們上半年的核心營業利潤率為 33.1%，第二季度為 31.2%。在淨收入線上，我們受益於第二季度的較低稅率，這是由於我們在主要司法管轄區提交 2021 年納稅申報表時的有利調整。預計季度之間的稅率差異將繼續存在，但我們仍預計全年的核心稅率為 18% 至 22%。第二季度核心每股收益為 1.72 美元，增長 89%。

We saw some FX headwinds following the strengthening of the U.S. dollar in the period, which impacted our revenue by more than $500 million in Q2 alone versus on a CER basis. If rates remained at the level seen at the end of June, we anticipate a mid-single-digit adverse FX impact on both total revenue and core EPS for the full year.

在此期間美元走強後，我們看到了一些外匯逆風，僅在第二季度就對我們的收入造成了超過 5 億美元的影響，而在 CER 基礎上。如果利率保持在 6 月底的水平，我們預計全年總收入和核心每股收益都會受到中個位數的不利外匯影響。

Please turn to Slide 11. Today, we are updating our full year guidance. We now anticipate total revenue at constant exchange rates to grow by low to mid-20s (sic) [low 20s] percentage, which reflects the strength of the underlying business and an updated outlook for our COVID-19 medicines. We expect COVID-19 revenues broadly flat to 2021 with, of course, a different mix of Vaxzevria and Evusheld.

請轉到幻燈片 11。今天，我們正在更新我們的全年指南。我們現在預計，按固定匯率計算的總收入將以 20 年代中期（原文如此）[low 20s] 的百分比增長，這反映了基礎業務的實力和我們 COVID-19藥物的最新前景。我們預計到 2021 年 COVID-19 收入將大致持平，當然，Vaxzevria 和 Evusheld 的組合會有所不同。

We're also updating our guidance for core operating expenses, which are now anticipated to grow by mid to high teens percentage. This, as Pascal touched upon in his introduction, is mainly driven by additional investment in R&D as we continue to invest in long-term growth including promising medicines such as Dato-DXd, new launches across the globe as well as broader investment in digital and AI capabilities, to name a few.

我們還更新了對核心運營費用的指導，現在預計這些費用將以中高比例增長。正如 Pascal 在他的介紹中提到的那樣，這主要是由對研發的額外投資推動的，因為我們繼續投資於長期增長，包括有前景的藥物，如 Dato-DXd、全球新推出的藥物以及對數字和人工智能功能，僅舉幾例。

Looking ahead, we expect our R&D expenses in the second half of the year to be broadly consistent with the first half as trials progress. We have had very limited divestments so far this year, and we now anticipate other operating income in the second half to be at similar levels as in the first half of around $200 million. Our 2022 outlook for China and emerging markets remains unchanged. Our core EPS guidance for the full year also remains unchanged, with an anticipated growth of mid- to high 20s percentage.

展望未來，隨著試驗的進展，我們預計下半年的研發費用將與上半年大致一致。今年到目前為止，我們的撤資非常有限，我們現在預計下半年的其他營業收入將與上半年相似，約為 2 億美元。我們對中國和新興市場的 2022 年展望保持不變。我們全年的核心每股收益指引也保持不變，預計增長率將達到 20% 的中高水平。

Beyond the specific guidance, like all other companies, we're also being impacted by the current macro environment, and we have seen a number of countries reporting high inflation numbers recently, which may ultimately also impact our cost base. You saw that our distribution costs increased by about 32% in the half versus 2021, reflecting not only higher freight rates and inflation, but also higher volumes, including Alexion. Unlike some other industries, we are limited in our ability to pass on cost increases to our customers.

除了具體指導之外，與所有其他公司一樣，我們也受到當前宏觀環境的影響，我們看到許多國家最近報告了高通脹數據，這最終也可能影響我們的成本基礎。您看到，與 2021 年相比，上半年我們的分銷成本增加了約 32%，這不僅反映了更高的運費和通貨膨脹，還反映了更高的銷量，包括 Alexion。與其他一些行業不同，我們將成本增加轉嫁給客戶的能力有限。

Please turn to Slide 12. We continue to see improvement in cash flow generation, and in the first half, our net cash inflow from operating activities increased by $1.7 billion to $4.5 billion. In the second quarter, we paid $775 million to Chugai following a legal settlement on Ultomiris. And in the first quarter, we paid the first of 3 payments, $920 million to the former shareholders of Acerta. The 2 remaining payments of similar amount will be paid in 2023 and 2024.

請轉到幻燈片 12。我們繼續看到現金流產生的改善，上半年，我們來自經營活動的淨現金流入增加了 17 億美元，達到 45 億美元。在對 Ultomiris 達成法律和解後，我們在第二季度向 Chugai 支付了 7.75 億美元。在第一季度，我們向 Acerta 的前股東支付了 3 筆款項中的第一筆，即 9.2 億美元。其餘兩筆金額相近的款項將在 2023 年和 2024 年支付。

As we have previously highlighted, that we also anticipate cash flows relating to prior business development transactions, including Daiichi, of just above $1 billion this year.

正如我們之前強調的那樣，我們還預計今年與包括 Daiichi 在內的先前業務發展交易相關的現金流量將略高於 10 億美元。

Our current net debt-to-EBITDA ratio is 3.5x. If adjusting for Alexion fair value inventory adjustment, which does not affect our cash flow, the ratio is 2.1x. Our capital allocation priorities remain unchanged, and we continue to invest in our business in order to deliver long-term sustainable growth. Consistent with our announcement in February, with an increase in dividend to an annualized $2.90 per share, the Board has approved an interim dividend for 2022 of $0.93 to be paid in September.

我們目前的淨債務與 EBITDA 比率為 3.5 倍。如果對不影響我們現金流的 Alexion 公允價值庫存調整進行調整，則該比率為 2.1 倍。我們的資本配置重點保持不變，我們繼續投資於我們的業務，以實現長期可持續增長。與我們在 2 月份的公告一致，隨著股息增加至年化每股 2.90 美元，董事會已批准 2022 年中期股息 0.93 美元，將於 9 月支付。

With that, I will hand over to Dave to take you through our oncology performance.

有了這個，我將交給戴夫帶你了解我們的腫瘤學表現。

Thank you, Aradhana. Slide 14, please. We're pleased to report that our oncology total revenue grew 22% year-over-year during the first half, underpinned by 18% growth in product sales. We saw double-digit product sales growth for Tagrisso, Imfinzi and Lynparza versus the prior year and also sequentially in the quarter, as well as very strong continuing momentum for both Calquence and Enhertu.

謝謝你，阿拉達納。請幻燈片 14。我們很高興地報告，我們的腫瘤學總收入在上半年同比增長 22%，這得益於產品銷售增長 18%。我們看到 Tagrisso、Imfinzi 和 Lynparza 的產品銷售與去年同期以及本季度環比均實現了兩位數的增長，Calquence 和 Enhertu 的持續增長勢頭也非常強勁。

Across regions, performance was nicely balanced with the U.S., Europe, emerging markets and established rest of world each also driving double-digit year-on-year growth.

在各個地區，美國、歐洲、新興市場和世界其他地區的表現都很好地平衡了，每個國家也推動了兩位數的同比增長。

Importantly, we're seeing positive signs of recovery in cancer diagnosis, testing and treatment rates as COVID-19 case and hospitalization rates improved over the last 6 months in many countries. For example, in the U.S., advanced breast cancer and ovarian cancer diagnosis rates have returned to pre-COVID baseline levels, and lung cancer is improved to 90% of baseline, trends were optimistic, will continue. In China, lockdowns in key cities have had an adverse impact on our medicines in the second quarter.

重要的是，隨著過去 6 個月許多國家的 COVID-19 病例和住院率有所改善，我們看到癌症診斷、檢測和治療率恢復的積極跡象。例如，在美國，晚期乳腺癌和卵巢癌的診斷率已經恢復到 COVID 之前的基線水平，肺癌改善到基線的 90%，趨勢樂觀，將繼續。在中國，主要城市的封鎖在第二季度對我們的藥品產生了不利影響。

Now I'm going to turn to greater detail on each of our key oncology medicines. Tagrisso global revenues grew by 14% in the first half. In the U.S., growth was 11% with Q2 growing at 17%, reflecting increased underlying demand and the normalization of inventory and gross to net impact seen in Q1.

現在，我將詳細介紹我們每種主要的腫瘤藥物。 Tagrisso 上半年的全球收入增長了 14%。在美國，增長率為 11%，第二季度增長率為 17%，反映了潛在需求的增加以及第一季度的庫存和總淨影響的正常化。

In the adjuvant setting, our efforts continue to build momentum. EGFR testing is now standard of care with rates greater than 80%. And importantly, adjuvant drug treatment rates have eclipsed 7 -- excuse me, 60% for the first time. With that said, there's still much work to do in terms of market education and driving stage shift to early disease.

在輔助環境中，我們的努力繼續建立勢頭。 EGFR 檢測現在是護理標準，比率超過 80%。重要的是，輔助藥物治療率首次超過 7——對不起，60%。話雖如此，在市場教育和推動階段向早期疾病轉移方面還有很多工作要做。

In Emerging Markets, revenues grew 17% in the half, driven by continued launch momentum, especially in LatAm, and significant volume growth in the first-line demand in China. As highlighted last quarter, volume growth in China has fully compensated for the lower NRDL price.

在新興市場，上半年收入增長了 17%，這得益於持續的發布勢頭，尤其是在拉丁美洲，以及中國一線需求的顯著增長。正如上個季度所強調的那樣，中國的銷量增長完全彌補了較低的 NRDL 價格。

On a sequential basis, EM revenues were broadly flat due to the impact of COVID-19 lockdowns in major cities in China.

由於中國主要城市 COVID-19 封鎖的影響，新興市場收入環比基本持平。

Turning now to Imfinzi. Global revenues grew 16% in the half and 20% in the second quarter, benefiting from recovery in diagnosis and chemoradiation rates in many regions. U.S. performance was robust, with sales growing 15% in the half and 22% in Q2 as we saw an encouraging rebound in the Pacific setting and early, spontaneous, non-promoted use in biliary tract cancer where the TOPAZ-1 data has been added as category 1 treatment in the NCCN guidelines this month.

現在轉向 Imfinzi。得益於許多地區診斷和放化療率的恢復，全球收入在上半年增長了 16%，第二季度增長了 20%。美國表現強勁，上半年銷售額增長 15%，第二季度增長 22%，因為我們看到太平洋地區出現了令人鼓舞的反彈，以及在已添加 TOPAZ-1 數據的膽道癌中的早期、自發、非推廣使用作為本月 NCCN 指南中的第 1 類治療。

In Europe, Imfinzi growth was up an impressive 29% for the half on strong uptake in small cell lung cancer based on CASPIAN an increasing use in Stage 3 lung following COVID-19 recovery. Across the globe, our teams are busily preparing for anticipated launches of TOPAZ-1 in and HIMALAYA in liver cancer.

在歐洲，由於基於 CASPIAN 的小細胞肺癌的強勁吸收，以及在 COVID-19 恢復後在 3 期肺中的使用增加，Imfinzi 的一半增長了令人印象深刻的 29%。在全球範圍內，我們的團隊正忙於為預期推出的 TOPAZ-1 和 HIMALAYA 肝癌治療做準備。

For Lynparza, we continue to solidify the brand as the leader in the global PARP inhibitor class. Product sales grew 18%, led by growth in adjuvant breast cancer following the U.S. approval based on the OlympiA Phase III trial and also supported by continued growth in HRD-positive first-line ovarian cancer and second-line castration-resistant prostate cancer.

對於 Lynparza，我們將繼續鞏固其品牌作為全球 PARP 抑製劑類別的領導者。產品銷售額增長了 18%，這主要得益於在 OlympiA III 期試驗獲得美國批准後輔助性乳腺癌的增長，並且還受到 HRD 陽性一線卵巢癌和二線去勢抵抗性前列腺癌的持續增長的支持。

Performance was seen across regions, with U.S. sales up 11%, Europe up 20% and Established Rest of World, up 27% in the half. Finally, emerging markets grew 32% on expanded patient access in ovarian cancer in China and other EM launches.

各個地區的表現都可以看到，美國銷售額增長 11%，歐洲增長 20%，世界其他地區增長 27%。最後，新興市場增長了 32%，原因是在中國擴大了卵巢癌患者的使用範圍以及其他新興市場的推出。

Turning to hematology. Calquence continues to show excellent momentum, with worldwide revenues up 87% versus the first half of 2021. In the U.S., Calquence has crossed 55% share of new BTKi class starts in first-line CLL, consolidating its position as the clear standard of care.

轉向血液學。 Calquence 繼續顯示出良好的勢頭，與 2021 年上半年相比，全球收入增長了 87%。在美國，Calquence 在一線 CLL 新 BTKi 類啟動中的份額已超過 55%，鞏固了其作為明確護理標準的地位.

In Europe, expansion continues, resulting in 26% of sequential growth from Q1 as new patient share continues to rise as we rapidly establish leadership in several major markets.

在歐洲，擴張仍在繼續，隨著我們在幾個主要市場迅速確立領導地位，新患者份額繼續上升，導致第一季度環比增長 26%。

And finally, for Enhertu. Total revenue was up 129% to $204 million. In the U.S., Enhertu has already achieved a leading new patient share of 35% in second-line HER2-positive metastatic breast cancer, rapidly displacing the prior standard of care. This is just 2 months after approval and launch based on the DESTINY-Breast03 Phase III trial. Europe and emerging markets have contributed nicely to growth as well based on launches in the third-line HER2-positive metastatic breast cancer.

最後，對於 Enhertu。總收入增長 129% 至 2.04 億美元。在美國，Enhertu 已經在二線 HER2陽性轉移性乳腺癌中取得了領先的 35% 的新患者份額，迅速取代了之前的護理標準。這距 DESTINY-Breast03 III 期試驗獲批並啟動僅 2 個月。基於三線 HER2 陽性轉移性乳腺癌的推出，歐洲和新興市場也為增長做出了很好的貢獻。

Following presentation in Q2 at ASCO and inclusion in the NCCN guidelines, we are preparing for anticipated launches in HER2 low metastatic breast cancer based on DESTINY-Breast04. Given the timing of those events, we don't believe growth for the half reflects much utilization yet in this setting.

在第二季度在 ASCO 上發表並納入 NCCN 指南之後，我們正在為基於 DESTINY-Breast04 的 HER2低轉移性乳腺癌的預期推出做準備。考慮到這些事件的發生時間，我們認為這一半的增長並未反映在這種情況下的大量利用率。

Across the globe, we are once again in an intense period of launch activity. We're just getting started with OlympiA and DESTINY-Breast03, and we hope soon that, that will be followed by DESTINY-Breast04, PROpel, HIMALAYA, TOPAZ-1, POSEIDON and DESTINY-Lung01 in the months ahead.

在全球範圍內，我們再次處於發射活動的緊張時期。我們剛剛開始使用 OlympiA 和 DESTINY-Breast03，我們希望不久之後，在接下來的幾個月中，DESTINY-Breast04、PROpel、HIMALAYA、TOPAZ-1、POSEIDON 和 DESTINY-Lung01 將緊隨其後。

As we look to the second half, we're also looking forward to seeing data readouts from EMERALD-1 Phase III trial of Imfinzi in local regional liver cancer and CAPItello291, the first Phase III readout for our AKT inhibitor, capivasertib, in HR+/ HER2-negative breast cancer. Collectively, this list, many of which represent blockbuster opportunities, will be key drivers of oncology growth next year and beyond.

展望下半年，我們也期待看到 Imfinzi 在局部區域肝癌中的 EMERALD-1 III 期試驗和 CAPItello291 的數據讀數，這是我們的 AKT 抑製劑 capivasertib 在 HR + / 中的第一個 III 期讀數HER2陰性乳腺癌。總的來說，這份名單中的許多代表著巨大的機遇，將成為明年及以後腫瘤學增長的關鍵驅動力。

I'll now hand over to Susan, who will cover the pipeline in greater detail.

我現在將移交給 Susan，她將更詳細地介紹管道。

Thank you, Dave. Please turn to Slide 15. I was very happy to be back in Chicago in June, where we once again demonstrated our scientific leadership in cancer research at this year's ASCO. During a plenary presentation, we presented Enhertu data, outlining unprecedented benefit in HER2-low metastatic breast cancer patients. This success unlocks further opportunity to utilize HER2-targeted therapies in HER2 low patients in breast cancer and beyond. The strength of the data was corroborated by the U.S. submission of DESTINY-Breast04 receiving a Priority Review.

謝謝你，戴夫。請轉到幻燈片 15。我很高興 6 月份回到芝加哥，在今年的 ASCO 上，我們再次展示了我們在癌症研究方面的科學領導地位。在全體會議上，我們展示了 Enhertu 數據，概述了 HER2 低轉移性乳腺癌患者的前所未有的益處。這一成功開啟了進一步的機會，在 HER2 低乳腺癌及其他患者中使用 HER2 靶向療法。美國提交的 DESTINY-Breast04 接受優先審查證實了數據的強度。

Also at ASCO, we presented results from the FAKTION trial with capivasertib in metastatic ER-positive breast cancer. Using next-generation sequencing, PI3K/AKT/PTEN pathway altered patients were identified and expanded biomarker subgroup analyses were performed. Patients in this subgroup saw an impressive 38.9 months of overall survival benefit versus 20 months in the fulvestrant monotherapy arm. PI3K/AKT/PTEN is the most frequently mutated pathway in breast cancer, and is very important as mutations can drive resistance to current endocrine therapies.

同樣在 ASCO，我們展示了 FAKTION 試驗用 capivasertib 治療轉移性 ER 陽性乳腺癌的結果。使用下一代測序，PI3K/AKT/PTEN 通路改變的患者被識別出來，並進行了擴展的生物標誌物亞組分析。該亞組患者的總生存期延長了 38.9 個月，而氟維司群單藥治療組為 20 個月。 PI3K/AKT/PTEN 是乳腺癌中最常見的突變途徑，並且非常重要，因為突變可以驅動對當前內分泌治療的抵抗。

Moving on to hematology. With the acquisition of TNB-486, a CD19xCD3 directed T-cell engager, we're advancing our ambition to deliver innovative new treatments across blood cancers. By generating new immune responses, T-cell engagers could potentially deliver benefit to cancer patients not currently responsive to immunotherapy.

繼續血液學。通過收購 TNB-486，一種 CD19xCD3 導向的 T 細胞接合劑，我們正在推進我們的雄心壯志，為血液癌症提供創新的新療法。通過產生新的免疫反應，T 細胞參與者可能為目前對免疫療法沒有反應的癌症患者帶來益處。

TNB-486 is currently in Phase I clinical trials as a monotherapy in relapsed or refractory B-cell non-Hodgkin lymphoma, with plans to expand into other lymphomas. Moving forward, we plan to develop TNB-486 as a monotherapy or in combination with other targeted and (inaudible) therapies in B-cell malignancies, including diffuse large B-cell lymphoma as well as follicular lymphoma.

TNB-486目前正處於 I 期臨床試驗中，作為複發或難治性 B 細胞非霍奇金淋巴瘤的單一療法，併計劃擴展到其他淋巴瘤。展望未來，我們計劃開發 TNB-486 作為單一療法或與 B 細胞惡性腫瘤的其他靶向和（聽不清）療法相結合，包括瀰漫性大 B 細胞淋巴瘤和濾泡性淋巴瘤。

Please turn to Slide 16. We look forward to this year's World Congress on Lung Cancer Conference in August, presenting data addressing advanced and resistant disease with targeted medicines and novel combinations. We'll present results from the SAVANNAH trial combining Tagrisso and Orpathys. Results showed a trend towards improved response rates with increasing levels of resistance, with an overall response rate of 32% in [all comers] And 49% in high-met aberration patients. We look forward to data from trials such as FLAURA2 and SAFFRON, broadening and elongating the level of clinical benefit Tagrisso can provide to patients.

請轉至幻燈片 16。我們期待今年 8 月舉行的世界肺癌大會，屆時將展示針對晚期和耐藥性疾病的數據以及靶向藥物和新組合。我們將展示結合 Tagrisso 和 Orpathys 的 SAVANNAH 試驗的結果。結果顯示，隨著抵抗力水平的提高，反應率有提高的趨勢，[所有參與者]的總體反應率為 32%，高變差患者的總體反應率為 49%。我們期待 FLAURA2 和 SAFFRON 等試驗的數據，擴大和延長泰瑞沙可以為患者提供的臨床益處水平。

We will present data from the TROPION-Lung02 trial, Dato-DXd plus checkpoint inhibitor pembrolizumab with or without platinum chemotherapy, demonstrating promising efficacy and tolerable safety in advanced non-small cell lung cancer patients without actionable genomic alterations. The response rate seen in the Dato-DXd and checkpoint inhibitor arm is much more impressive than what we've seen with either monotherapy. The results are in line with the BEGONIA trial for Dato-DXd + Imfinzi, where the 74% response rate gives us confidence both from tolerability and efficacy standpoint over and above what we've seen with IO + chemo.

我們將展示 TROPION-Lung02 試驗的數據，Dato-DXd 加檢查點抑製劑 pembrolizumab 聯合或不聯合鉑類化療，在沒有可操作基因組改變的晚期非小細胞肺癌患者中展示有希望的療效和可耐受的安全性。在 Dato-DXd 和檢查點抑製劑組中看到的反應率比我們在任何一種單一療法中看到的都要令人印象深刻。結果與 Dato-DXd + Imfinzi 的 BEGONIA 試驗一致，其中 74% 的反應率使我們從耐受性和療效的角度對 IO + 化療所看到的結果充滿信心。

Looking forward to next year, we have an exceptionally high level of news flow upcoming for oncology. Key charts to look out for in 2023 are the TROPION-Lung01 results with Dato-DXd in the first half as well as AEGEAN, [EFS and BR31] readouts to bring Imfinzi earlier in the treatment paradigm for non-small cell lung cancer, increasing the chance of cure.

展望明年，我們將迎來非常高水平的腫瘤學新聞。 2023 年需要關注的關鍵圖表是上半年使用 Dato-DXd 的 TROPION-Lung01 結果以及 AEGEAN、[EFS 和 BR31] 讀數，以使 Imfinzi 在非小細胞肺癌的治療範式中更早，增加治癒的機會。

I'm now going to hand over to Ruud to cover BioPharmaceuticals. Please advance to Slide 17.

我現在要交給 Ruud 來報導生物製藥。請前進到幻燈片 17。

Thank you, Susan. Now turning to Slide 18. Looking at our BioPharmaceuticals business, CVRM total revenues were up 19% on a pro forma basis to $4.6 billion. R&I was up 3% to $3 billion, and V&I delivered total revenues of $2.8 billion. Farxiga achieved an impressive 62% growth driven by strong demand in type 2 diabetes, heart failure and chronic kidney disease.

謝謝你，蘇珊。現在轉到幻燈片 18。看看我們的生物製藥業務，CVRM 的總收入在備考基礎上增長了 19%，達到 46 億美元。 R&I 增長 3% 至 30 億美元，V&I 的總收入為 28 億美元。在 2 型糖尿病、心力衰竭和慢性腎病的強勁需求的推動下， Farxiga 實現了令人印象深刻的 62% 的增長。

Farxiga is the fastest-growing SGLT2i brand globally, and strong performance across all regions provides confidence in continued growth. We reported headline results in the delivery trial for Farxiga in heart failure with preserved ejection fraction, which Mene will cover in more detail. But needless to say, we are excited about the potential opportunity to expand use in this underserved population.

Farxiga 是全球增長最快的 SGLT2i 品牌，所有地區的強勁表現為持續增長提供了信心。我們報告了 Farxiga 治療射血分數保留的心力衰竭的分娩試驗的主要結果，Mene 將對此進行更詳細的介紹。但不用說，我們對在這個服務不足的人群中擴大使用的潛在機會感到興奮。

In Respiratory & Immunology, strong growth from Fasenra and new launch medicines, Breztri, Saphnelo and Tezspire was partly offset by Pulmicort's continued decline in China following VBP inclusion last October.

在呼吸與免疫學領域，Fasenra 和新上市藥物 Breztri 、 Saphnelo 和 Tezspire 的強勁增長被 Pulmicort 在去年 10 月 VBP 納入後在中國的持續下滑部分抵消。

Fasenra continued its market leadership position in eosinophilic asthma across major markets, delivering 18% growth in the half. We are excited by the launch of Tezspire in severe asthma. In its first 4 quarters since launch, Tezspire achieved 13% new-to-brand market share, and we are pleased to see over 60% of new-to-brand share coming from the non-IL-5 class with minimal impact on Fasenra.

Fasenra 在主要市場繼續其在嗜酸性哮喘領域的市場領導地位，上半年實現了 18% 的增長。我們對 Tezspire 在嚴重哮喘中的推出感到興奮。自推出以來的前 4 個季度，Tezspire 獲得了 13% 的新品牌市場份額，我們很高興看到超過 60% 的新品牌份額來自非 IL-5 類別，而對 Fasenra 的影響最小.

We continue to see demand growth for Saphnelo in systemic lupus erythematosus. And in the U.S., new-to-brand prescriptions reached 24% of the biological class in the second quarter.

我們繼續看到 Saphnelo 在系統性紅斑狼瘡中的需求增長。在美國，新品牌處方在第二季度達到了生物類的 24%。

Within V&I, for Vaxzevria total revenues reached $1.6 billion in the half, fulfilling the majority of initial contracts. As Pascal mentioned, Vaxzevria, our COVID-19 vaccine, is estimated to have saved over 6 million lives. This analysis is based on data from Imperial College and published in The Lancet.

在 V&I 中，Vaxzevria 上半年的總收入達到 16 億美元，完成了大部分初始合同。正如 Pascal 所提到的，我們的 COVID-19 疫苗 Vaxzevria 估計已經挽救了超過 600 萬人的生命。該分析基於帝國理工學院的數據並發表在《柳葉刀》上。

Evusheld, our long-acting antibody, delivered $914 million, reflecting additional contracts signed globally.

我們的長效抗體 Evusheld 交付了 9.14 億美元，反映了全球簽署的額外合同。

Please turn to Slide 19. In Emerging Markets, total revenue was $6.2 billion in the half. Emerging Markets' growth rate, including the impact of Vaxzevria, was 16%, and this was split between ex-China emerging market sales, which grew 46%, and China, where sales declined 5%. Excluding the impact of Vaxzevria, ex-China emerging markets grew 48%.

請轉到幻燈片 19。在新興市場，上半年的總收入為 62 億美元。新興市場的增長率（包括 Vaxzevria 的影響）為 16%，其中中國以外的新興市場銷售額增長了 46%，而中國的銷售額下降了 5%。排除 Vaxzevria 的影響，除中國以外的新興市場增長了 48%。

As mentioned previously, the delayed VBP 7 tender process completed in July, and we expect implementation in quarter 4 of this year with full impact on [silicon stock] in 2023. We reiterate our guidance and still expect total revenue for emerging markets to grow by mid-single digits in 2022 with mid-single-digit decline in China.

如前所述，延遲的 VBP 7 招標過程已於 7 月完成，我們預計將在今年第 4 季度實施，並在 2023 年對 [矽庫存] 產生全面影響。我們重申我們的指導，並仍預計新興市場的總收入將增長2022 年中個位數，中國將出現中個位數下降。

I will now hand over to Mene to cover the R&D advancements in the period.

我現在將交給梅內來介紹這一時期的研發進展。

Thanks, Ruud. Please turn to Slide 20. In May, we reported that DELIVER trial showed that Farxiga achieved a clinically meaningful reduction in cardiovascular death or worsening heart failure in patients with preserved ejection fraction. Together with the successful DAPA-HF trial, DELIVER demonstrates Farxiga's efficacy across the full spectrum of heart failure regardless of ejection fraction, and we look forward to presenting DELIVER's full results at the ESC in Barcelona in August.

謝謝，路德。請轉到幻燈片 20。5 月，我們報導 DELIVER 試驗表明 Farxiga 在射血分數保留的患者中實現了具有臨床意義的心血管死亡或心力衰竭惡化的減少。與成功的 DAPA-HF 試驗一起，DELIVER 證明了 Farxiga 在所有心力衰竭方面的療效，無論射血分數如何，我們期待在 8 月在巴塞羅那的 ESC 上展示 DELIVER 的全部結果。

Also in the quarter, together with our partner Ionis, we disclosed positive high-level results from the NEURO-TTRansform trial in hereditary transthyretin-mediated amyloid polyneuropathy. A debilitating disease that can lead to impaired motor function. Eplontersen delivered a clinically meaningful improvement in the patient's modified neuropathy impairment score plus 7.

同樣在本季度，我們與我們的合作夥伴 Ionis 一起，披露了 NEURO-TTRansform 試驗在遺傳性轉甲狀腺素介導的澱粉樣多發性神經病中的積極高水平結果。一種使人衰弱的疾病，可導致運動功能受損。 Eplontersen 在患者的改良神經病變損傷評分加 7 方面提供了具有臨床意義的改善。

In our V&I portfolio, new data published in The New England Journal of Medicine showed that Evusheld retains neutralizing activity against the Omicron variants BA.5, BA.4 and BA.2, all of which are highly prevalent globally today. And while Evusheld remains highly effective at preventing COVID-19, we are cognizant that the virus will continue to evolve. And in the quarter, we licensed an early-stage portfolio of COVID-19 antibodies from RQ Biotechnologies.

在我們的 V&I 產品組合中，發表在《新英格蘭醫學雜誌》上的新數據表明，Evusheld 保留了對 Omicron 變體 BA.5、BA.4 和 BA.2 的中和活性，所有這些都在當今全球高度流行。儘管 Evusheld 在預防 COVID-19 方面仍然非常有效，但我們認識到該病毒將繼續發展。在本季度，我們從 RQ Biotechnologies 獲得了早期 COVID-19抗體組合的許可。

Looking ahead to the next 18 months, we have more data to come from Farxiga with the DAPA-MI Phase III trial for non-diabetic patients with myocardial infarction. And we're excited about forthcoming Phase III readouts with Fasenra in 3, eosinophilic-driven diseases: EOE, HES and EGPA. Later this year, we also anticipate seeing further Phase II data from our SOLANO study, confirming that AZD8233 has the potential to be a best-in-class molecule in terms of its LDL-reducing activity in patients with dyslipidemia, and that's targeting PCSK9.

展望未來 18 個月，我們有更多來自 Farxiga 的數據，用於非糖尿病心肌梗塞患者的 DAPA-MI III 期試驗。我們對 Fasenra 即將在 3 種嗜酸性粒細胞驅動疾病中的 III 期讀數感到興奮：EOE、HES 和 EGPA。今年晚些時候，我們還預計從我們的 SOLANO 研究中看到更多的 II 期數據，證實 AZD8233 在血脂異常患者中降低 LDL 的活性方面有潛力成為同類最佳的分子，並且針對 PCSK9。

We have over 10 mid-stage clinical trial readouts in the next 12 to 18 months that will fuel the next wave of significant investment decisions, including Farxiga combinations, our MPO inhibitor, and tozorakimab, our anti-IL-33 monoclonal antibody.

在未來 12 至 18 個月內，我們有超過 10 個中期臨床試驗讀數，這將推動下一波重大投資決策，包括我們的 MPO 抑製劑 Farxiga 組合和我們的抗 IL-33單克隆抗體 tozorakimab。

Please move to Slide 21. We were also delighted with The New England Journal of Medicine publication and proud to have developed such an efficacious medicine with nirsevimab. RSV, as you know, is a leading cause of lower respiratory tract infections such as bronchiolitis or pneumonia as well as hospitalization in infants, and these data show for the first time the potential to significantly protect all infants through their first RSV season with a single-dose immunization, and we look forward to working with health authorities to bring nirsevimab to infants as quickly as possible.

請移至幻燈片 21。我們也對《新英格蘭醫學雜誌》的出版感到高興，並為使用 nirsevimab 開發出如此有效的藥物而感到自豪。如您所知，RSV 是導致下呼吸道感染（如細支氣管炎或肺炎）以及嬰兒住院的主要原因，這些數據首次表明，在所有嬰兒的第一個 RSV 季節，一個單一的疫苗有可能顯著保護所有嬰兒-劑量免疫，我們期待與衛生當局合作，盡快將 nirsevimab 帶給嬰兒。

Please now turn to Slide 22, and I will now hand over to Marc to cover rare diseases.

現在請轉到幻燈片 22，我現在將交給 Marc 來報導罕見疾病。

Thank you, Mene. Please turn to Slide 23. In the first half, Rare Disease contributed $3.5 billion in total revenues, representing year-on-year pro forma increase of 10%. In the second quarter, we recognized certain one-off pricing adjustment in the international region. Excluding these one-offs, pro forma growth in the first half was 8%. Emerging market sales were $206 million in the first half, impacted by order timing in certain tender markets.

謝謝你，梅內。請轉至幻燈片 23。上半年，罕見病貢獻了 35 億美元的總收入，同比增長 10%。在第二季度，我們確認了國際地區的某些一次性定價調整。剔除這些一次性因素，上半年的備考增長率為 8%。上半年新興市場銷售額為 2.06 億美元，受某些招標市場訂單時間的影響。

In the second quarter, the C5 franchise delivered durable pro forma growth of 9%. The slowing growth of Soliris reflects successful conversion to Ultomiris. New market expansion and strong launch uptake in generalized myasthenia gravis in the U.S. drove Ultomiris to 31% in the second quarter. While it is still early in the myasthenia gravis launch at quarter end, approximately 1/3 of Ultomiris initiation with complement naive patients, which gives us confidence in the ability to expand our addressable population to approximately 30,000 patients in the United States.

在第二季度，C5 特許經營權實現了 9% 的持久備考增長。 Soliris 增長放緩反映了成功轉換為 Ultomiris。新的市場擴張和美國廣泛性重症肌無力的強勁上市推動 Ultomiris 在第二季度達到 31%。雖然它在季度末的重症肌無力推出仍處於早期階段，但大約 1/3 的 Ultomiris 起始於未接受過補充的患者，這使我們有信心將我們的可尋址人群擴大到美國約 30,000 名患者。

Beyond the -- of Ultomiris initiation with complement naive patients, which gives us confidence in the ability to expand our addressable population to approximately 30,000 patients in the United States.

除了對補體天真的患者啟動 Ultomiris 之外，這使我們有信心將我們的可尋址人群擴大到美國約 30,000 名患者。

Beyond the C5 franchise, Strensiq grew 18% in the quarter, driven by strong underlying demand and initiation trends in the U.S. Lastly, Koselugo demonstrated substantial growth in the quarter, benefiting from rare disease organizational realignments resulting in increased demand and market expansion.

除了 C5 特許經營權之外，在美國強勁的潛在需求和啟動趨勢的推動下， Strensiq 在本季度增長了 18%。最後，Koselugo 在本季度表現出顯著增長，這得益於罕見病組織重組導致需求增加和市場擴張。

Please turn to Slide 24. During the period, we reported remarkable Phase III data from the Ultomiris CHAMPION trial in neuromyelitis optica. As shown on the Kaplan-Meier curve, there were 0 adjudicated relapses on the slide that you can see. This is this horizontal blue line, 0 adjudicated relapses observed in patients receiving Ultomiris, and importantly, this effect continued out to 73.5 weeks. This exceptional data not only represent the opportunity to bring an innovative new medicine to NMO patients, but also offers another example of the consistently strong data generated by C5 franchise, Soliris and Ultomiris, in neurological indications.

請轉到幻燈片 24。在此期間，我們報告了來自視神經脊髓炎的 Ultomiris CHAMPION 試驗的出色 III 期數據。如 Kaplan-Meier 曲線所示，您可以在載玻片上看到 0 次判定復發。這是這條水平藍線，在接受 Ultomiris 的患者中觀察到 0 次裁定的複發，重要的是，這種效果持續到 73.5 週。這一非凡的數據不僅代表了為 NMO 患者帶來創新新藥的機會，而且還提供了另一個例子，證明了 C5 特許經營公司 Soliris 和 Ultomiris 在神經系統適應症方面持續產生的強大數據。

Looking ahead, we're excited to continue to deliver on our pipeline with anticipated readouts for Soliris in Guillain-Barré syndrome, which is now expected in the second half of this year, and the headline results of our first-generation novel oral Factor-D inhibitor, danicopan, in PNH, with EVH expected in the first half of 2023.

展望未來，我們很高興繼續交付我們的產品線，預計將在今年下半年推出針對格林-巴利綜合徵的 Soliris 的預期讀數，以及我們第一代新型口服因子的主要結果- PNH 中的 D 抑製劑 danicopan，預計 2023 年上半年出現 EVH。

Lastly, before I turn the call back to Pascal for closing commentary, I would like to highlight 2 important milestones for Alexion. This year, Alexion marks its 30th anniversary in rare disease and also the first anniversary of the deal closure. With immense gratitude, I would like to thank our Alexion colleagues for their continued commitment to pushing the boundaries of science and accelerating innovation to develop life-changing therapies for those living with rare disease around the world.

最後，在我將電話轉回給 Pascal 進行結束評論之前，我想強調一下 Alexion 的兩個重要里程碑。今年，Alexion 是其在罕見病領域成立 30 週年，也是交易完成一周年。懷著無限的感激之情，我要感謝我們的 Alexion 同事，他們一直致力於推動科學的界限和加速創新，為世界各地的罕見病患者開發改變生活的療法。

With that, please turn to Slide 25, and I will hand over the call to Pascal.

有了這個，請轉到幻燈片 25，我將把電話交給 Pascal。

Thank you very much, Marc. Please move to the next slide. .

非常感謝你，馬克。請移至下一張幻燈片。 .

Together with the Board, I'm pleased to announce Michel Demare will take over from Leif Johansson as Chair following the 2023 AGM. I've worked closely with Michel since he joined our Board in 2019, and I look forward to our continued partnership in his new role. I'd like to thank Leif for his commitment to AstraZeneca over the years and through the transition period. I've had an amazing 10-year period working with Leif, and we've gone through a lot together. And I would really like to thank him and the Board for their continued support over the last 10 years that have taken us from where we are -- where we were in 2013 to where we are today, in a very, very different place. And it's been really a fantastic experience working with Leif. We've been a tremendous team. And I know Michel and I will be working together and forming an excellent team for the many years to come.

我很高興與董事會一起宣布 Michel Demare 將在 2023 年年度股東大會後接替 Leif Johansson 擔任主席。自 Michel 於 2019 年加入我們的董事會以來，我一直與他密切合作，我期待我們在他的新職位上繼續合作。我要感謝 Leif 多年來和過渡期間對阿斯利康的承諾。我和 Leif 一起工作了 10 年，這令人驚嘆，我們一起經歷了很多。我真的要感謝他和董事會在過去 10 年中的持續支持，這使我們從 2013 年的位置到今天的位置，在一個非常非常不同的地方。和 Leif 一起工作真的是一次很棒的經歷。我們一直是一支很棒的團隊。而且我知道米歇爾和我將在未來的許多年裡一起工作並組建一支優秀的團隊。

Now, we'd like to close with Slide 27. We continue to execute on our strategic priorities, which will position AstraZeneca to deliver long-term growth. Our robust life cycle management continues to support our top line growth, and in the half, we delivered on key Phase III life cycle management trials, including Ultomiris in NMOSD and Farxiga in heart failure with preserved ejection fraction. We continue to invest in our pipeline in order to achieve our strategic growth ambition, and we remain open to strategic business development such as our acquisition of TeneoTwo, CD19xCD3 T-cell engager in hematology.

現在，我們想以幻燈片 27 結束。我們將繼續執行我們的戰略重點，這將使阿斯利康能夠實現長期增長。我們強大的生命週期管理繼續支持我們的收入增長，在上半年，我們交付了關鍵的 III 期生命週期管理試驗，包括 NMOSD 的 Ultomiris 和射血分數保留的心力衰竭的 Farxiga 。我們將繼續投資於我們的管道以實現我們的戰略增長目標，我們仍然對戰略業務發展持開放態度，例如我們收購 TeneoTwo，CD19xCD3 T 細胞從事血液學。

Importantly, we have a long runway for most of our medicines in terms of loss of exclusivity, which should provide confidence in our sustainable growth. Our company has shown -- has grown stronger in 2022 both in terms of revenue and pipeline development. And as you have seen and heard today, we are investing thoughtfully to continue to grow our business at an industry-leading right through 2025 and beyond. We want and we believe we can be a growth story for the many years to come. As you can see on this slide, we have everything we need to grow and we continue building on what we have.

重要的是，我們的大多數藥物在失去排他性方面都有很長的路要走，這應該會為我們的可持續增長提供信心。我們公司已經表明——在收入和管道開發方面，到 2022 年都變得更加強大。正如您今天所見所聞，我們正在深思熟慮地投資，以在 2025 年及以後繼續以行業領先的方式發展我們的業務。我們希望並且我們相信我們可以成為未來許多年的增長故事。正如您在這張幻燈片上看到的那樣，我們擁有發展所需的一切，我們將繼續在現有的基礎上發展。

At the same time, we want to continue driving our focus on improving operating margin. And as you probably remember, we said our goal is to get to mid to high 30s in the mid to long term. We're very committed to this. We're making progress in that direction. And the success we are experiencing with our top line revenue allows us to stay focused on this goal of improving margin, but at the same time, continue to invest strongly in our pipeline so that we can indeed deliver top line growth -- strong growth post 2025.

同時，我們希望繼續將重點放在提高營業利潤率上。您可能還記得，我們說過我們的目標是在中長期內達到 30 多歲。我們非常致力於這一點。我們正在朝著這個方向取得進展。我們在頂線收入方面所取得的成功使我們能夠繼續專注於提高利潤率的目標，但與此同時，繼續大力投資於我們的管道，以便我們確實能夠實現頂線增長——強勁增長後2025 年。

Thank you all for joining. We'll now take your questions, and I will hand the call back to Andy.

謝謝大家的加入。我們現在將回答您的問題，我會將電話轉回給安迪。

If you turn to Slide 28, we will now go to the Q&A. (Operator Instructions) Now, let's take the first question from the conference call.

如果您轉到幻燈片 28，我們現在將進入問答環節。 （操作員說明）現在，讓我們從電話會議中提出第一個問題。

Thanks, Andy. So the first part is -- the first question, sorry, is from Richard Parkes at BNP Paribas. Richard, over to you.

謝謝，安迪。所以第一部分是-- 抱歉，第一個問題來自法國巴黎銀行的Richard Parkes。理查德，交給你了。

Another chance later on this afternoon, and it's on U.S. drug pricing reform. It's looking increasingly likely that we see enactment to that in the -- over the summer period. So I wondered if you could just help us maybe get some indications for your portfolio? Two aspects to that. Medicare Part D restructuring could have some positive and some negative implications for your portfolio. So can you help us understand how that might balance out?

今天下午晚些時候還有一次機會，它是關於美國藥品定價改革的。看起來我們越來越有可能在夏季看到這一點的頒布。所以我想知道你是否可以幫助我們為你的投資組合獲得一些跡象？有兩個方面。 Medicare D 部分重組可能會對您的投資組合產生一些積極和消極的影響。那麼你能幫助我們了解如何平衡嗎？

And then in terms of direct negotiation, you've got a few drugs in Tagrisso, Lynparza, Calquence at some point could come into that basket. So could you just help us understand maybe the probabilities any of those drugs, at least, gets included in the first couple of rounds of that negotiation process?

然後就直接談判而言，你在 Tagrisso、Lynparza 有一些藥物，Calquence 在某個時候可能會進入那個籃子。那麼，您能否幫助我們了解這些藥物中的任何一種至少被包括在該談判過程的前幾輪談判中的可能性？

Thanks, Richard. So maybe I could ask Dave to cover part of your question. And Ruud, you've also been, of course, following this very closely. You could add to this. Over to you, Dave.

謝謝，理查德。所以也許我可以請戴夫回答你的部分問題。 Ruud，當然，你也一直在密切關注這一點。你可以添加到這個。交給你了，戴夫。

Thanks, Pascal. Richard, you have the 2 elements, Part D and negotiation. I guess there's a third element as well which is inflation penalties, which just to address right at the bet, we don't see that as having much impact. If any, we've been pretty responsible and below inflation rates on price increases historically.

謝謝，帕斯卡。理查德，你有兩個要素，D 部分和談判。我想還有第三個因素是通貨膨脹懲罰，這只是為了解決賭注，我們認為這不會產生太大影響。如果有的話，我們一直非常負責任，並且歷史上價格上漲的通貨膨脹率低於通貨膨脹率。

I think that between now and when negotiation starts in 2026 based on the current writing, that the impact overall of Part D reform is quite manageable. As you point out, there are going to be some impacts in oncology that are negative over the period. That said, that's offset by some opportunities that come through patient affordability for greater adherence and compliance across the portfolio, and I think, in particular, in our BioPharmaceuticals unit.

根據目前的寫作，我認為從現在到 2026 年開始談判時，D 部分改革的總體影響是可以控制的。正如您所指出的，在此期間將對腫瘤學產生一些負面影響。也就是說，這被患者負擔能力帶來的一些機會所抵消，這些機會可以提高整個投資組合的依從性和合規性，我認為尤其是在我們的生物製藥部門。

In terms of negotiation, we do see negotiation as a bad precedent for innovation. And we think that it's going to have an impact on the speed with which innovation, particularly in areas of small populations and high unmet needs, how companies and sponsors are thinking through that.

在談判方面，我們確實將談判視為創新的不良先例。我們認為這將對創新的速度產生影響，特別是在人口少和需求未得到滿足的領域，以及公司和讚助商如何思考這一點。

In terms of AstraZeneca-specific impacts, I do think that starting in 2027 and beyond, as you point out, that Tagrisso certainly becomes a possibility for being one of the medicines that could fall into this. The rules specifically for how that's being contemplated are not yet clear. They're the top 50 drugs, and there will be some selection that's made by that period of time. But I think that we are looking at a 2027 and beyond time period, so it's certainly kind of post medium term where I think we start to see the impact coming from the negotiation portion.

就阿斯利康（AstraZeneca）的具體影響而言，我確實認為，從 2027 年及以後開始，正如您所指出的，泰瑞沙肯定有可能成為可能落入其中的藥物之一。具體如何考慮的規則尚不清楚。它們是排名前 50 的藥物，在那個時期會有一些選擇。但我認為我們正在考慮 2027 年及以後的時間段，所以這肯定是中期後的時期，我認為我們開始看到談判部分的影響。

Ruud, do you want to talk about some of the BioPharma-specific elements?

路德，你想談談一些生物製藥特有的元素嗎？

Yes. So very quickly, and you were mentioning Dave, great adherence is a potential upside for a few products in the BioPharma business. We know that persistency rates in the U.S. are always somewhat lower than, for example, in Europe due to affordability. Out of pocket costs are relatively high in the United States. So hopefully, this part, the redesign will deliver an opportunity for patients to stay long on therapy. And of course, that will benefit some our products in the BioPharma business unit.

是的。很快，你提到了戴夫，對生物製藥業務中的一些產品來說，良好的依從性是一個潛在的優勢。我們知道，由於負擔能力，美國的持續率總是比歐洲低一些。在美國，自付費用相對較高。因此，希望這部分的重新設計將為患者提供一個長期接受治療的機會。當然，這將使我們在生物製藥業務部門的一些產品受益。

Thank you, Ruud. Thank you, Dave. Sachin Jain, Bank of America, what's your question?

謝謝你，路德。謝謝你，戴夫。 Sachin Jain，美國銀行，你的問題是什麼？

Can you just give some color on how you think about cost -- how are you thinking about cost lines?

您能否就您對成本的看法發表一些看法——您如何看待成本線？

Can you hear me?

你能聽到我嗎？

Yes, yes. Go ahead. Sorry.

是的是的。前進。對不起。

Sorry. How you're thinking about cost lines within that? So R&D spend clearly flexing up. Any color where you think that goes versus the existing 21% to 22% of sales. And any additional color you can give on SG&A offset for that? And just what flex do you think exists in you getting to the top versus bottom end of that margin range?

對不起。您如何考慮其中的成本線？因此，研發支出明顯增加。您認為與現有 21% 到 22% 的銷售額相比的任何顏色。您可以為此在 SG&A 偏移量上提供任何其他顏色嗎？您認為在達到該邊距範圍的頂端和底端時存在什麼彈性？

Second question is for Susan on amivantamab. Updated PFS data in The World Lung abstract, it looks like PFS trending towards 30 months. Obviously, impressive versus the 18 to 19, with Tagrisso accepting. It's a very small end. Just wondering if you could update us on your competitive thoughts on Tagrisso there? I think on the ASCO call, you'd noted IV discontinuation, seem that 10%, 15% being lower. And therefore, any caution on that potentially hitting? Just wondering whether your thought process is shifting to all there?

第二個問題是關於 amivantamab 的 Susan。更新了 The World Lung 摘要中的 PFS 數據，看起來 PFS 趨向於 30 個月。顯然，與 18 比 19 相比，Tagrisso 接受了，令人印象深刻。這是一個非常小的結局。只是想知道您是否可以向我們介紹您對 Tagrisso 的競爭看法？我認為在 ASCO 電話會議上，您注意到 IV 停藥，似乎 10%、15% 更低。因此，對這種潛在的打擊有什麼警告嗎？只是想知道您的思維過程是否正在轉移到那裡？

Sachin. So Aradhana, do you want to take the first one, and Susan the second?

薩欽。所以阿拉達納，你想拿第一個，蘇珊拿第二個嗎？

Thanks, Sachin, for your question. On R&D, as we noted and given the number of positive readouts we've had, clearly, that's ungated a number of additional studies. And so we continue to invest in R&D. I think we've been fairly consistent around how much we want to invest in R&D on an ongoing basis in the sort of low 20 range, and we're sort of consistent with that. As I also mentioned, we do expect the second half to be somewhat consistent with the first half for this year. And going forward, obviously, we'll give guidance when we do for 2023.

謝謝，薩欽，你的問題。在研發方面，正如我們所指出的，並且考慮到我們已經獲得的積極讀數的數量，顯然，這並沒有限制一些額外的研究。所以我們繼續投資於研發。我認為我們一直非常一致地希望在 20 低的範圍內持續投資於研發，我們也與此一致。正如我也提到的，我們確實預計今年下半年與上半年的情況會有些一致。顯然，展望未來，我們將在 2023 年提供指導。

On SG&A, we continue to drive improving operating margins. You've seen that our margin trajectory continues to improve and also specifically note that, that margin achievement is with a much lower contribution of other income that we expect this year. So we're continuing to drive SG&A and we'll continue to drive efficiency, and we remain committed to our operating margin ambition that we've communicated previously. Susan?

在 SG&A 方面，我們繼續推動提高營業利潤率。您已經看到我們的利潤率軌跡繼續改善，並特別指出，利潤率的實現與我們今年預期的其他收入的貢獻相比要低得多。因此，我們將繼續推動 SG&A，我們將繼續提高效率，我們將繼續致力於實現我們之前傳達的運營利潤率目標。蘇珊？

Sure. Thanks for the question. So we have a multipronged approach to combinations with Tagrisso. Firstly, we have the FLAURA2 study, which is our combination with Tagrisso plus doublet platinum-based chemotherapy. I would point you to encouraging Phase II data from the [OPAL] study, which was presented at ASCO.

當然。謝謝你的問題。所以我們有一個多管齊下的方法來與 Tagrisso 組合。首先，我們進行了 FLAURA2 研究，這是我們與 Tagrisso 加雙藥鉑類化療的組合。我會指出你鼓勵來自 [OPAL] 研究的 II 期數據，該研究在 ASCO 上展示。

Looking at this combination with platinum-based chemotherapy plus pemetrexed which showed in an end of 67 patients, a 91% response rate, a 2-year landmark progression-free survival of 70%, which compares very favorably with the data in an end of 20 that was presented from the CHRYSALIS data. FLAURA2 is fully recruited, and it reads out in the first half of 2023.

看看這種與鉑類化療加培美曲塞的組合，在 67 名患者中顯示，91% 的反應率，70% 的 2 年標誌性無進展生存率，這與結束時的數據相比非常有利20 來自 CHRYSALIS 數據。 FLAURA2 已滿員，2023 年上半年讀出。

In addition, of course, we've got the combination, as you mentioned, with savolitinib, which is ongoing in Phase III in the SAFFRON study. And again, we have data from the SAVANNAH study, which supported at Phase III start with encouraging response rates, particularly in the high MET amplified subgroup.

此外，當然，正如您所提到的，我們已經獲得了與 savolitinib 的組合，該組合正在 SAFFRON 研究的 III 期進行。再一次，我們有來自 SAVANNAH 研究的數據，該研究在 III 期開始時得到了令人鼓舞的響應率，特別是在高 MET 放大亞組中。

We've also got combinations that are ongoing with ADC including patritumab, the HER3-directed antibody drug conjugate, as well as with Dato-DXd. And I'll note that Dato-DXd in patients with actionable genomic alterations post-treatment with those targeted therapies showed a 35% response rate. So we're encouraged about the general potential for combinability for Tagrisso.

我們還有與 ADC 進行的組合，包括 patritumab、HER3 導向的抗體藥物偶聯物，以及與 Dato-DXd 的組合。我會注意到，在使用這些靶向療法治療後具有可操作基因組改變的患者中，Dato-DXd 顯示出 35% 的反應率。因此，我們對 Tagrisso 可組合性的一般潛力感到鼓舞。

I think in addition, Sachin, to what Susan laid out, maybe just 2 other components that I'd like to share.

除了 Susan 所闡述的內容之外，我認為 Sachin 可能只是我想分享的其他 2 個組件。

I mean, I think the first piece when we take a look at Tagrisso, and I mentioned this in some of the opening remarks, we are seeing from FLAURA the duration of therapy is increasing, and frankly, longer than what we saw in the study. And I think, in part, this owes to a pretty favorable side effect profile of monotherapy in Tagrisso. I think we see pretty low mid-teens level of grade 3 treatment-related adverse events. And I think that we're already seeing quite a bit longer than from both of the sets of combinations.

我的意思是，我認為當我們看一下 Tagrisso 時的第一部分，我在一些開場白中提到了這一點，我們從 FLAURA 看到治療持續時間正在增加，坦率地說，比我們在研究中看到的要長.我認為，部分原因在於 Tagrisso 單藥治療的副作用非常有利。我認為我們看到 3 級治療相關不良事件的青少年水平相當低。而且我認為我們已經看到了比這兩組組合更長的時間。

I think with that being said, I would expect to see some utilization in certain patients of the combination of both FLAURA2 and the [J&J] combo are positive, and I still think that the majority of the utilization that you're going to see in the metastatic setting comes from the monotherapy at this stage.

我認為話雖如此，我希望在某些患者中看到 FLAURA2 和 [J&J] 組合的組合是積極的，而且我仍然認為您將看到的大部分應用在轉移環境來自這個階段的單一療法。

And I'd also add, we continue to grow with key catalysts of ADAURA. LAURA is on the horizon. Susan and I have both talked about FLAURA2 when we've initiated the ADAURA2 study, which I think continues to build on life cycle plan in Tagrisso that I think remains vibrant.

我還要補充一點，我們在 ADAURA 的關鍵催化劑下繼續發展。勞拉即將出現。當我們啟動 ADAURA2 研究時，Susan 和我都談到了 FLAURA2，我認為該研究繼續建立在我認為仍然充滿活力的 Tagrisso 生命週期計劃的基礎上。

Thanks, Dave. Mark Purcell at Morgan Stanley. Mark, over to you.

謝謝，戴夫。摩根士丹利的馬克·珀塞爾。馬克，交給你。

A question on Evusheld and [amafantinib]. Can you help us understand the level of investment you're putting behind this asset and the durability you expect going forward? Mene, you've mentioned the [RQ] Biotechnology deal with early-stage antibodies. So just the level of ambition there would be great.

關於 Evusheld 和 [amafantinib] 的問題。您能否幫助我們了解您對該資產的投資水平以及您對未來預期的耐用性？梅內，你提到了 [RQ] 生物技術處理早期抗體的問題。因此，只有雄心壯志的水平就會很大。

Just a follow-up to what Sachin just asked. Do you expect to see combination use of Tagrisso with amafantinib as well? It would be useful to get your perspective there.

只是對 Sachin 剛剛提出的問題的跟進。您是否也希望看到 Tagrisso 與阿馬凡替尼聯合使用？在那裡獲得您的觀點會很有用。

And then the last one just on Dato-DXd. You're clearly a priority asset where you're looking to invest more. Could you help us understand the ambitions outside lung cancer at this point?

然後是 Dato-DXd 上的最後一個。您顯然是您希望進行更多投資的優先資產。您能幫助我們了解肺癌之外的野心嗎？

Thanks, Mark. So maybe we can start with Evusheld, it's kind of 2 questions here. One is the investments and the ambition for this product, and two is durability.

謝謝，馬克。所以也許我們可以從 Evusheld 開始，這裡有 2 個問題。一是對這個產品的投資和野心，二是耐用性。

Thanks for the question. And first of all, we are pleased to see strong demand, increased demand for Evusheld because it is clear that it's really important to protect the immunocompromised patients in the COVID-19 due to the fact that they are not able to develop their immune response after vaccination. We do believe that, that demand will continue, and therefore, it is really important to make sure that we do our best to educate and increase the awareness for both patients and HCPs to be able to use Evusheld to protect patients who are in need.

謝謝你的問題。首先，我們很高興看到強勁的需求，對 Evusheld 的需求增加，因為很明顯，保護 COVID-19 中免疫功能低下的患者非常重要，因為他們在感染後無法產生免疫反應接種疫苗。我們確實相信，這種需求將繼續存在，因此，確保我們盡最大努力教育和提高患者和 HCP 的意識，以便能夠使用 Evusheld 來保護有需要的患者，這一點非常重要。

Therefore, our investments are increasing, and we want to resource that in the proper way to make sure that we drive demand and fulfill and satisfy the needs that exists to protect immunocompromised patients.

因此，我們的投資正在增加，我們希望以適當的方式為其提供資源，以確保我們推動需求並滿足和滿足保護免疫功能低下患者的現有需求。

Durability.

耐用性。

And then given on the durability, I think it's in our increase or updated guidance. It's clear that we do see increased demand this year. It's always difficult to predict and forecast COVID-19 medicine given the evolving and dynamic environment. But I can say that we feel -- that we feel strong about the durable need for Evusheld, specifically given the fact that Evusheld is the only monoclonal antibody approved for prophylaxis, and equally, the only one that has retained neutralizing activity in that space versus all different Omicron variants.

然後給出耐久性，我認為這是我們增加或更新的指導。很明顯，我們確實看到今年的需求有所增加。鑑於不斷變化的動態環境，預測和預測 COVID-19 藥物總是很困難。但我可以說我們感覺——我們對 Evusheld 的持久需求感到強烈，特別是考慮到 Evusheld 是唯一被批准用於預防的單克隆抗體，同樣，唯一在該領域保留中和活性的單克隆抗體與所有不同的 Omicron 變體。

And the reason for that is that Evusheld was designed as a combination of the 2 monoclonal antibodies with a different but complementary activity against the Omicron variant. And therefore, it was designed to evade the resistance in the future variants. So we stay positive and optimistic that it will retain its activity versus new variants.

其原因是 Evusheld 被設計為兩種單克隆抗體的組合，對 Omicron 變體具有不同但互補的活性。因此，它旨在逃避未來變體中的阻力。因此，我們保持樂觀和樂觀，認為它將保留其活動而不是新變種。

Thanks, Iskra. Maybe just to add. If you look at COVID today, you could reasonably maybe argument that the most important thing to do today is not necessarily to boost people who are healthy, it's actually to protect those who are immunocompromised and vulnerable. So those are the people who have cancer, people who have been transplanted, people who may have HIV or some other immune conditions. Because these people need to be protected, vaccines don't work at all or not very well.

謝謝，火星報。也許只是為了補充。如果你今天看看 COVID，你可能會合理地爭論說，今天最重要的事情不一定是讓健康的人受益，實際上是保護那些免疫功能低下和易受傷害的人。因此，這些人是患有癌症的人、接受過移植的人、可能感染 HIV 或其他一些免疫疾病的人。因為這些人需要受到保護，所以疫苗根本不起作用或效果不佳。

Two, is they represent 30% to 40% patients who are hospitalized with this COVID. And three is, because they are immunocompromised, they tend to keep the virus in their body longer, and they are a source of mutations and variants.

第二，他們是否代表了 30% 到 40% 的 COVID 住院患者。三是，由於它們的免疫功能低下，它們往往會使病毒在體內停留的時間更長，並且它們是突變和變異的來源。

So for all those reasons, it's important to protect these people, and it should be #1 priority. The issue is, we need to make sure physicians and patients are well aware of the product if we want to make it sustainable. And as a result, the investments we are doing now is really important so we can make sure patients and physicians are educated and then they continue using it.

因此，出於所有這些原因，保護這些人很重要，這應該是第一要務。問題是，如果我們想讓它可持續發展，我們需要確保醫生和患者充分了解該產品。因此，我們現在所做的投資非常重要，因此我們可以確保患者和醫生接受教育，然後他們繼續使用它。

And beyond that, the only question is, as Iskra said, will the variant emerge that become resistant? So far hasn't been the case, because the product is very cleverly developed with 2 antibodies. But beyond this, we still -- and I think, Mene, mentioned it, we are working on the next generation, just in case a variant would become resistant to Evusheld.

除此之外，唯一的問題是，正如 Iskra 所說，是否會出現具有抗藥性的變體？到目前為止還不是這樣，因為該產品非常巧妙地開發了 2 種抗體。但除此之外，我們仍然——我認為，Mene 提到了它，我們正在研究下一代，以防萬一變體對 Evusheld 產生抗藥性。

So we've got good hope it's sustainable, durable, but of course, we don't know. It's hard to predict the future with COVID as we all know.

所以我們很有希望它是可持續的、耐用的，但當然，我們不知道。眾所周知，很難預測 COVID 的未來。

The other question was combination, again, and that was -- Susan, do you want to cover that?

另一個問題是組合，再次，那就是——蘇珊，你想涵蓋那個嗎？

Sure, thank you. So Dato-DXd, the -- as I mentioned at the ASCO IR event, we're planning 5 new Phase III trials which will start over the next 12 to 18 months, so by the end of 2023. So we're obviously investing in lung cancer and in breast cancer. We've recently had the start of the TROPIAN-Breast02 study in local recurrence, inoperable metastatic triple-negative breast cancer.

當然，謝謝。所以 Dato-DXd，正如我在 ASCO IR 活動中提到的那樣，我們計劃在未來 12 到 18 個月內開始 5 個新的 III 期試驗，因此到 2023 年底。所以我們顯然正在投資在肺癌和乳腺癌中。我們最近開始了針對局部復發、無法手術的轉移性三陰性乳腺癌的 TROPIAN-Breast02 研究。

And we have ongoing [PAM tumor] study, which is looking at the potential for this medicine across a range of other tumor types. And I'd remind you that TROP2 expression is actually highly expressed across a range of different tumor types. So I do think there is potential for this molecule beyond breast and lung cancer.

我們正在進行 [PAM 腫瘤] 研究，正在研究這種藥物在一系列其他腫瘤類型中的潛力。我要提醒你，TROP2 的表達實際上在一系列不同的腫瘤類型中高度表達。所以我確實認為這種分子在乳腺癌和肺癌之外還有潛力。

Dave, anything you want to add on?

戴夫，你有什麼要補充的嗎？

On Dato, I think that Dato has the opportunity to be one of the most significant medicines within the portfolio. And I think that the TROPION-Lung01 data is obviously going to be the first proof case of that. But I think that if we've got the ability to be able to just replace systemic chemotherapy in late-line lung cancer alone, that the opportunity is quite significant. And then as we think about how a biomarker might open it up to other places, I think the future is bright.

關於 Dato，我認為 Dato 有機會成為產品組合中最重要的藥物之一。我認為 TROPION-Lung01 數據顯然將成為第一個證明案例。但我認為，如果我們能夠僅在晚期肺癌中替代全身化療，那麼這個機會就非常重要。然後，當我們考慮生物標誌物如何將其打開到其他地方時，我認為未來是光明的。

I think also, Mark, you asked a question about expectations around Tagrisso, amavantinab utilization. I mean, obviously, that utilization would be spontaneous off-label, and I think probably it could only occur in the U.S. And so just based on that, while that may be something that I could envision taking place, I don't think that it would affect demand in material way in terms of what I'd be expecting for Tagrisso.

我還想，馬克，你問了一個關於泰瑞沙（Tagrisso）的預期問題，阿萬替尼的使用。我的意思是，顯然，這種使用將是自發的標籤外，而且我認為它可能只能在美國發生。所以只是基於此，雖然這可能是我可以預見的事情，但我不認為那就我對 Tagrisso 的期望而言，它會以物質方式影響需求。

Maybe just to add to what was said and link it back to our investment in R&D. I mean, you heard Dave say Dato-DXd has the potential to be a very, very large product, and we have all seen the Enhertu results and Enhertu can also be a very, very large product. Now the thing is we -- to achieve full potential, we have to develop those agents across a whole range of indications.

也許只是為了補充所說的內容並將其與我們在研發方面的投資聯繫起來。我的意思是，你聽說 Dave 說 Dato-DXd 有潛力成為一個非常非常大的產品，我們都看到了 Enhertu 的成果，Enhertu 也可以成為一個非常非常大的產品。現在的問題是我們——為了充分發揮潛力，我們必須在整個適應症範圍內開發這些藥物。

And beyond those 2 products, we have a whole range of products in oncology, we have a (inaudible) in cardiovascular medicines, we have tozorakimab. We have a whole number of other products including in rare disease. And so when you consider all of this, you really have to think, unless something really very unexpected happens, we should be a growth company. But we need to resource this product and make them big, big product like they deserve to be and get to their full potential.

除了這兩種產品之外，我們還有一系列的腫瘤產品，我們有（聽不清）心血管藥物，我們有 tozorakimab。我們有很多其他產品，包括罕見病產品。因此，當您考慮所有這些時，您真的必須考慮，除非發生非常出乎意料的事情，否則我們應該是一家成長型公司。但是我們需要為這個產品提供資源，讓它們像它們應得的那樣大，大的產品，並充分發揮它們的潛力。

Andrew Baum at CC, Andrew, over to you.

CC 的 Andrew Baum，Andrew，交給你了。

Firstly, on Evusheld. Could you update us on the anticipated timing for the FDA approval and also some indication? I'm sure you've been busy trying to build capacity. Where you think capacity could land by the end of next year? I'm just trying to work out how quickly you can leverage the enormous unmet medical need as well as your hematology, oncology and [autoimmune] field forces, which will feed into the at-risk patient population, and use the proceeds to sort of bridge the OpEx demands of the rest of your portfolio. So if you could talk to the limitations and how quickly you can overcome them and how much demand do you think you can grow, assuming the efficacy remains intact? So that's the first question.

首先，關於 Evusheld。您能否向我們介紹 FDA 批准的預期時間以及一些跡象？我敢肯定，你一直在忙於建設能力。您認為到明年年底產能會降落在哪裡？我只是想弄清楚你能多快利用巨大的未滿足的醫療需求以及你的血液學、腫瘤學和 [自身免疫] 領域的力量，這些力量將進入高危患者群體，並將收益用於排序橋接其他投資組合的運營支出需求。所以，如果你能談談限制，你能多快克服它們，你認為你可以增長多少需求，假設療效保持不變？所以這是第一個問題。

The second question is on China. [President Xi] has warned President Biden that the U.S. is playing with fire with Pelosi's visit. There's obviously a lot of geopolitical risk globally. I know that you have the largest Chinese business among the majors, and you have worked hard to build that securing relationships, local manufacturing. But I'm just wondering how has the Board considers other measures such as a partial IPO of the Chinese business with the Chinese listing akin to try and minimize the risk in case there's some escalation here?

第二個問題是關於中國的。 [習主席] 警告拜登總統，美國正在與佩洛西的訪問玩火。全球顯然存在很多地緣政治風險。我知道你們在各大巨頭中擁有最大的中國業務，並且你們努力建立這種穩固的關係，即本地製造。但我只是想知道董事會如何考慮其他措施，例如在中國上市的情況下對中國企業進行部分首次公開募股，以盡量降低風險，以防事態升級？

And then finally, perhaps you could update us how interactions between your lawyers and Merck's laws have gone in relation to the PARP-1 asset that you have, and Merck's belief they have some ownership or rights on that product?

最後，也許您可以向我們介紹您的律師與默克法律之間的互動如何與您擁有的 PARP-1 資產相關，以及默克認為他們對該產品擁有某些所有權或權利？

Let me just take a couple of things quickly. First of all, I'm very happy that Andy was not more successful than I was before limiting you guys to one question at a time. And those are 3 great questions, Andrew.

讓我快速處理幾件事情。首先，我很高興安迪沒有比我在一次限制你們一次回答一個問題之前更成功。這是 3 個很好的問題，安德魯。

And the second comment I will make is we don't communicate with our friends at Merck's lawyers. We talk to them, and of course, the lawyer gets involved at some point. But I just want to say we've had a tremendously positive collaboration with the team at Merck. And maybe, let me cover this part one question quickly, is we certainly have had such a great collaboration. We're very much inclined to collaborate with Merck on the PARP-1. The question is under what conditions and what timing and how do we do it? But I can't say we will do it, but it's certainly a very strong consideration for us to do it and continue the fantastic collaboration.

我要說的第二條評論是，我們不與默克律師事務所的朋友交流。我們與他們交談，當然，律師有時也會參與其中。但我只想說，我們與默克的團隊進行了非常積極的合作。也許，讓我快速介紹一下第一部分的問題，我們是否確實進行瞭如此出色的合作。我們非常傾向於在 PARP-1 上與默克公司合作。問題是在什麼條件下，什麼時間點，我們怎麼做？但我不能說我們會這樣做，但對於我們來說，這樣做並繼續進行精彩的合作肯定是一個非常強烈的考慮。

And Dave, if you have anything you want to add, you can add it a bit later if you want, no, yes.

Dave，如果您有任何想要添加的內容，您可以稍後再添加，不，是的。

So maybe let's start with Evusheld. Iskra, 2 questions for you, the approval and the capacity.

所以也許讓我們從 Evusheld 開始。 《火星報》，給你 2 個問題，批准和能力。

Yes. So we are progressing with many regulatory bodies around the world, the FDA included. As you probably know, we received approval for prophylaxis already in many countries including Europe, U.K., Canada, Australia and many others, and we have the emergency approval in U.S. and we are working closely with FDA for the final approval of the prophylaxis.

是的。因此，我們正在與世界各地的許多監管機構取得進展，包括 FDA。您可能知道，我們已經在包括歐洲、英國、加拿大、澳大利亞和許多其他國家在內的許多國家獲得了預防性治療的批准，並且我們在美國獲得了緊急批准，我們正在與 FDA 密切合作以最終批准預防性治療。

Equally, you probably know that we recently announced the Phase III trial of the treatment of the out of the hospital patients, and we do progress with the submissions of the regulatory approvals for the treatment indication. We do expect approval in Europe in the second half of this year as well as progressing in the U.S., Japan and China with our submissions as previously I commented.

同樣，您可能知道我們最近宣布了治療出院患者的 III 期試驗，並且我們在提交治療適應症的監管批准方面取得了進展。正如我之前評論的那樣，我們確實希望今年下半年在歐洲獲得批准，並在美國、日本和中國取得進展。

As you fairly noticed, there is a strong and important unmet need in this space. And therefore, we are doing our best to increase the capacity and make sure we are able to supply as many patients as we can across the globe. From the previous discussions and announcements we made, we're continuing to increase the supply, and we are confident that we will be able to supply all the contracts that we currently have. And going forward, we are continuously doing and increasing the supply and the capacity as much as we can.

正如您所注意到的，在這個領域存在一個強大而重要的未滿足需求。因此，我們正在盡最大努力提高容量，並確保我們能夠在全球範圍內為盡可能多的患者提供服務。從我們之前的討論和公告來看，我們正在繼續增加供應，我們有信心能夠供應我們目前擁有的所有合同。展望未來，我們將繼續盡可能多地增加供應和產能。

And on the [Phase 1] deployment, Andrew, you raised an important question and we have field forces across haematology, immunology, et cetera. So we can deploy the sales force. But I think your question about approval, which [arise] an important one. We need to get approval -- full approval, not an EUA, to be able to fully promote. And its fundamental, so we established the product and the use.

在 [第一階段] 部署中，安德魯，你提出了一個重要問題，我們在血液學、免疫學等領域都有現場力量。所以我們可以部署銷售人員。但我認為你關於批准的問題是一個重要的問題。我們需要獲得批准——完全批准，而不是 EUA，才能充分推廣。以及它的根本，所以我們確立了產品和用途。

With China, let me just say quickly, and I'll hand over to Leon to comment more on the situation on the ground in China. Essentially, we don't comment on what consideration we would do, but we're always looking at various scenarios for the different parts of the business. So in Southern China, we are looking at what is the best way to continue operating in China. The approach we've always taken in China has been we are in China for China. And then more -- in the last few years, our approach has been -- we've been -- we are in China for the world. What that means is we're in China to bring our medicines to Chinese patients, but we're also in China to help the world. We export from China, and we are now connecting to Chinese innovation and looking to partner. We've set up an investment fund that is investing in biotech companies in China, and we're looking at how can we tap into Chinese innovation to benefit patients around the world.

關於中國，讓我快點說，我將交給萊昂更多地評論中國當地的情況。本質上，我們不會評論我們會做哪些考慮，但我們一直在研究業務不同部分的各種場景。因此，在華南地區，我們正在研究繼續在中國開展業務的最佳方式。我們在中國一直採取的方法是我們在中國為中國服務。然後更多——在過去的幾年裡，我們的方法一直是——我們一直——我們在中國是為了世界。這意味著我們在中國是為了將我們的藥物帶給中國患者，但我們也在中國幫助世界。我們從中國出口，現在我們正在連接中國的創新並尋找合作夥伴。我們設立了一個投資基金，投資於中國的生物技術公司，我們正在研究如何利用中國的創新來造福世界各地的患者。

So our approach has really always been to be in China for China and for the world. And the way we operate keep -- is always within that framework. But beyond this, it's hard to comment on what consideration or what options we are actually looking at.

所以我們的做法一直是在中國為中國和世界服務。我們的運作方式始終保持在該框架內。但除此之外，很難評論我們實際在考慮什麼考慮或選擇什麼。

Leon, do you want to comment a little bit on the situation on the ground in China?

Leon，你想對中國的實際情況發表一點看法嗎？

Yes. I think the China government is after COVID situation, 0 COVID policies still continue. So maintaining -- avoiding disruption on logistics and supply chain and also protecting foreign company investment are the 2 most important priority for the Chinese government.

是的。我認為中國政府在 COVID 情況之後，0 COVID 政策仍在繼續。因此，維護——避免物流和供應鏈中斷以及保護外國公司投資是中國政府的第二個最重要的優先事項。

So our strategy in China is very clear, is to speed up our global pipeline into China because our global pipeline is still in China, we lag a little bit behind. So we are getting Enhertu D-BO3 and D-BO4 approval next year. And the PTK Acala is very important product, so we also launch Acala next year to indication. And (inaudible) the Evusheld, we are also submitting this year and also, hopefully, we can get approval later this year. So launching [Zidua] next year and launching 2 most important rare disease products and many new indications. So 2023 and 2024 and 2025, the next 3 years will be critical for our new innovative pipeline to succeed in China.

所以我們在中國的戰略非常明確，就是加快我們進入中國的全球管道，因為我們的全球管道還在中國，我們有點落後。所以我們明年將獲得 Enhertu D-BO3 和 D-BO4 的批准。而PTK Acala 是非常重要的產品，所以我們明年也推出Acala 來進行說明。並且（聽不清）Evusheld，我們也在今年提交，希望我們能在今年晚些時候獲得批准。所以明年推出[Zidua]，推出2個最重要的罕見病產品和許多新的適應症。因此，2023 年、2024 年和 2025 年，未來 3 年對於我們新的創新管道在中國取得成功至關重要。

But of course, at the same time, you can clearly see Pulmicort get a hit. And our large products, Seloken and Crestor (inaudible) getting to VBP one by one. But we are still able to maintain all multiple channel promotions to keep loyal user as much as possible. So I think at the same time, we are slowing down the time on the VBP portfolio, and at the same time, pushing a new indication, life cycle indication of large products like Tagrisso and Farxiga. So -- and also launching a new pipeline on top of all these growth.

但當然，與此同時，您可以清楚地看到 Pulmicort 受到了打擊。而我們的大型產品 Seloken 和 Crestor（聽不清）則一一進入 VBP。但是我們仍然能夠維持所有的多渠道促銷活動，以盡可能地留住忠實用戶。所以我認為，與此同時，我們正在放慢 VBP 產品組合的時間，同時推動一個新的適應症，即 Tagrisso 和 Farxiga 等大型產品的生命週期適應症。所以 - 並且還在所有這些增長的基礎上啟動了一條新的管道。

So I think our strategy is to make clear like Pascal said, we -- on top of our global innovation, we also established the fund with CICC and tap into local innovation. Hopefully, we can work closely, I think, with FibroGen to roxa in China, work with Hutchison to do (inaudible) in China. So that's just the beginning. I think we will have, in the future, more new products in China for China and in China for globe.

所以我認為我們的策略是像帕斯卡所說的那樣明確，我們 - 在我們的全球創新之上，我們還與中金公司建立了基金並利用本地創新。希望我們可以密切合作，我認為，與 FibroGen 到 roxa 在中國，與和記黃埔一起在中國做（聽不清）。所以這只是開始。我想我們未來會有更多的新產品在中國為中國和中國為全球。

Thanks, Leon. So the next question is Adam Karlsson at ABG. Adam, over to you.

謝謝，萊昂。所以下一個問題是 ABG 的 Adam Karlsson。亞當，交給你了。

First off the back of the (inaudible) Farxiga Phase IIb study and CKD being pushed into H1 next year. Just your current level of confidence or thinking on the prospect of getting Farxiga combinations approved of coming off patent?

首先是（聽不清）Farxiga IIb 期研究和 CKD 將於明年進入 H1 階段。只是您目前的信心水平或對 Farxiga 組合獲得專利批准的前景的想法？

And then secondly, on inflationary impact, and I guess, particular personnel cost. How much, if any, of that impact have you seen already? And how should we be thinking about the timing of that impact in either the second half or next year?

其次，關於通貨膨脹的影響，我猜，特別是人員成本。您已經看到了多少（如果有的話）影響？我們應該如何考慮下半年或明年的影響時間？

Thanks, Adam.

謝謝，亞當。

Mene, do you want to take the first one, and Aradhana, the second one about inflation?

梅內，你想拿第一個和阿拉達納，關於通貨膨脹的第二個嗎？

Okay. So the -- so first of all, just to remind you, the loss of exclusivity of Farxiga isn't a point in time. It's a range across multiple markets, and our revenues are split pretty well across all the regions. So we have quite a broad time frame in which to get the combinations launched.

好的。所以 - 首先，只是提醒你， Farxiga 的排他性喪失不是一個時間點。這是一個跨越多個市場的範圍，我們的收入在所有地區都分佈得很好。因此，我們有一個相當廣泛的時間框架來啟動組合。

But irrespective of that, the 2 combinations that we have moving forward, the MR modulator and the endothelin antagonist, are both self-sufficient business cases in their own right. And as we've said, we're expecting to get data for both of those by the first half of next year.

但不管怎樣，我們正在推進的兩種組合，MR 調節劑和內皮素拮抗劑，本身都是自給自足的商業案例。正如我們所說，我們希望在明年上半年獲得這兩個數據。

Now in terms of the mechanisms, these are both well precedented mechanisms. So as long as the molecules behave themselves, we're optimistic. But until we have data in hand, I won't be too optimistic. But I think once we get hopefully positive data, then I think we're full throttle to pivotal studies and trying to launch as soon as we can and hopefully within that time frame.

現在就機製而言，這些都是有先例的機制。所以只要分子表現自己，我們就很樂觀。但在我們掌握數據之前，我不會太樂觀。但我認為，一旦我們獲得有希望的積極數據，那麼我認為我們將全力以赴進行關鍵研究，並試圖盡快啟動，並希望在那個時間範圍內啟動。

I think maybe what I could add also separate from the combinations is that as Mene said, the product expiry is probably over time. But on top of it, if you look at the sales that Ruud showed you a bit earlier, the U.S. in the global sales is not the usual 50%, 60% of global sales. And you see here the potential of a drug that is addressing a big unmet need, and so a lot of sales are outside the U.S.

我想也許我還可以添加與組合分開的是，正如梅內所說，產品到期可能會隨著時間的推移而過期。但最重要的是，如果你看一下 Ruud 早些時候向你展示的銷售額，美國在全球銷售額中的佔比並不是通常的 50%、60%。你在這裡看到了解決巨大未滿足需求的藥物的潛力，因此很多銷售都在美國以外。

What that means is even when we lose patent protection in the U.S., the products or elsewhere, the product is not going to collapse. We're going to have a more a slower decline and so more time to launch those combinations and keep maintain this product.

這意味著即使我們在美國、產品或其他地方失去專利保護，產品也不會崩潰。我們將會有更緩慢的下降，因此有更多的時間來推出這些組合併繼續維護這個產品。

Aradhana?

阿拉達納？

Sure.

當然。

I think on inflation, as I mentioned, we are obviously seeing some impact of inflation, particularly in distribution costs. But we continue to monitor this. Our business is very resilient. We continue to innovate, so I think pricing of drugs and so forth has to be correlated with value. But this is something that we'll continue to monitor in terms of impact it has on our business.

我認為關於通貨膨脹，正如我所提到的，我們顯然看到了通貨膨脹的一些影響，特別是在分銷成本方面。但我們會繼續對此進行監控。我們的業務非常有彈性。我們不斷創新，所以我認為藥品等的定價必須與價值相關聯。但我們將繼續監控它對我們業務的影響。

Thanks, Aradhana.

謝謝，阿拉達納。

Tim Anderson, Wolfe Research. Tim, over to you.

蒂姆安德森，沃爾夫研究。蒂姆，交給你了。

On datopotamab, on TROPION-LUNG01, what do you think good results would need to be for Astra and investors to say, wow, this is like a very promising new drug? So what's realistic to expect in terms of things like hazard ratio and tolerability and safety?

在 datopotamab 上，在 TROPION-LUNG01 上，您認為 Astra 和投資者需要什麼好的結果才能說，哇，這就像一個非常有前途的新藥？那麼在風險比、耐受性和安全性等方面，什麼是現實的期望呢？

And then on Tagrisso and amivantamab, again, can Astra clarify its views on how often things that c-MET amplification is the driver of Tagrisso resistance? Because that's really what J&J is, and amivantamab success is most dependent on in that MARIPOSA trial. And the literature suggests it's not that high, maybe it's 20% or something, but I know that different estimates are out there.

然後在 Tagrisso 和 amivantamab 上，Astra 能否再次澄清其關於 c-MET 放大多久是 Tagrisso 耐藥性驅動因素的觀點？因為這就是 J&J 的真正意義，而 amivantamab 的成功最依賴於 MARIPOSA 試驗。文獻表明它並沒有那麼高，也許是 20% 左右，但我知道存在不同的估計。

So maybe the second question is for Susan. The first one, do you want to cover it, Dave, or?

所以也許第二個問題是給蘇珊的。第一個，你想覆蓋它嗎，戴夫，還是？

Sure. I think that in terms of what we see in TROPION-Lung01, you've got to compare that to the background of what we see from second line plus docetaxel, which is the comparator arm utilization, and the results that we see from that docetaxel in second, third line lung cancer has pretty poor response rates in that 5% to 20% range, depending on what you look at. And progression-free survival that again is, I think, relatively short, kind of in the 6 months and below range.

當然。我認為就我們在 TROPION-Lung01 中看到的情況而言，您必須將其與我們從二線加多西他賽中看到的背景進行比較，這是比較臂利用率，以及我們從多西他賽中看到的結果在二線、三線肺癌中，反應率在 5% 到 20% 的範圍內非常差，具體取決於您所看到的情況。我認為，無進展生存期也相對較短，在 6 個月及以下範圍內。

So certainly, when we kind of think about the opportunities to see what investors should be enthusiastic about, I think that some of the early data that we're already beginning to see within the abstract, I think, compares quite favorably to that. I don't know, Susan, if you want to speak to any of those elements. But I think that the other piece that I would say, Tim, that's really important here is that for all of the advancements that have been made in advanced lung cancer through checkpoints and checkpoints plus chemotherapy, the overwhelming majority of patients progress on those regimens, and they find themselves on systemic chemotherapies. And so it is a pretty enormous unmet need that this study seeks to address.

所以當然，當我們考慮有機會看到投資者應該對什麼充滿熱情時，我認為我們已經開始在摘要中看到的一些早期數據，我認為，與此相比相當有利。我不知道，蘇珊，如果你想和這些元素中的任何一個說話。但我認為我要說的另一部分，蒂姆，在這裡非常重要的是，對於晚期肺癌通過檢查點和檢查點加化療取得的所有進展，絕大多數患者在這些方案上取得進展，他們發現自己正在接受全身化療。因此，這項研究試圖解決一個非常巨大的未滿足需求。

Susie, do you want to comment at all on what we're seeing so far?

蘇西，你想對我們目前看到的情況發表評論嗎？

Yes. So as you're aware, the data we've already published shows a 28% response rate at the 6 mg per kg dose in the median response duration of 10.5 months. So again, if you put that into the context of what Dave just said about the expectation for current standard of care chemotherapy, I think you're seeing improvement.

是的。如您所知，我們已經發布的數據顯示，在 10.5 個月的中位反應持續時間中，每公斤劑量 6 毫克的反應率為 28%。再說一次，如果你把它放在戴夫剛才所說的關於當前護理化療標準的期望的背景下，我認為你看到了改善。

And then in terms of tolerability, a couple of things to note. First of all, the rate of interstitial lung disease is low with datopotamab deruxtecan than we've seen with Enhertu. What we do see is stomatitis as a dose-limiting toxicity, and we are investing in patient and investigator education about the management of the side effects and also digital health tools to help manage how patients get through that. So I think there are ways in which we can manage those side effects to really represent an overall benefit risk profile that's quite attractive in this setting.

然後在耐受性方面，有幾點需要注意。首先，使用 datopotamab deruxtecan 的間質性肺病發生率低於使用 Enhertu 的情況。我們確實看到口腔炎是一種劑量限制性毒性，我們正在對患者和研究人員進行有關副作用管理的教育，以及幫助管理患者如何度過難關的數字健康工具。所以我認為我們可以通過一些方法來管理這些副作用，以真正代表在這種情況下非常有吸引力的整體收益風險概況。

I think the second thing is -- that David alluded to is that across the program, we'll continue to look for opportunities to further refine the patient population that's best to treat as we move beyond TROPION-Lung01 into other settings.

我認為第二件事是——大衛提到的是，在整個項目中，隨著我們從 TROPION-Lung01 轉移到其他環境，我們將繼續尋找機會進一步完善最適合治療的患者群體。

And then I think your question about the level of MET overexpression and amplification as a resistance mechanism to Tagrisso. What we've seen is in the range of 15% to 30% range. So 15% when you're looking at circulating tumor DNA, but you can't underestimate the rate of MET amplification using ctDNA alone. If you look in tissue, it can be at the higher end of that range. So something in that range is what we're expecting.

然後我認為你關於 MET 過度表達和放大水平作為對 Tagrisso 的抗性機制的問題。我們看到的是在 15% 到 30% 的範圍內。因此，當您查看循環腫瘤 DNA 時為 15%，但您不能低估僅使用 ctDNA 的 MET 擴增率。如果您查看組織，它可能位於該範圍的較高端。所以這個範圍內的東西就是我們所期待的。

And I think, Tim, just maybe to add onto the -- back to the question on data. The [docetaxel] said it's less than 6, which is true. It's probably if we gave kind of accurate 3 to 4 months is what we're seeing. So that's what we need to be beating within this.

我想，蒂姆，也許只是補充一下——回到數據問題。 [多西他賽] 說它小於 6，這是真的。如果我們給出準確的 3 到 4 個月，這可能就是我們所看到的。所以這就是我們需要在其中擊敗的內容。

Thanks.

謝謝。

James Gordon, go ahead. Go ahead, James.

詹姆斯·戈登，繼續。繼續，詹姆斯。

Two questions.

兩個問題。

First question on lung cancer. So if FLAURA2 is positive, that presumably does read to the Tagrisso plus DS-1062 the ORCHARD data. Could that be a pivotal data? Or when might you be able to have pivotal data for Tagrisso plus an ADC for EGFR patients? And then given what we saw at World Lung for 1602-plus KEYTRUDA, fair to assume that you're going to do that in all comers who don't have EGFR mutation. So would it be plausible like within the next 12 months that effectively DS-1062 would be going after every one in lung cancer, either with Tagrisso if they've got the mutations or with KEYTRUDA if they don't have EGFR mutations? Is that the big picture plan for lung cancer?

第一個關於肺癌的問題。因此，如果 FLAURA2 為正值，則可能會讀取到 Tagrisso 和 DS-1062 的 ORCHARD 數據。這可能是關鍵數據嗎？或者你什麼時候才能獲得 Tagrisso 的關鍵數據以及 EGFR 患者的 ADC？然後考慮到我們在 World Lung 上看到的 1602+ KEYTRUDA 的情況，公平地假設您將在所有沒有 EGFR 突變的人中這樣做。那麼，在接下來的 12 個月內，DS-1062 將有效地追踪每一位肺癌患者，無論是使用 Tagrisso，如果他們有突變，還是使用 KEYTRUDA，如果他們沒有 EGFR 突變，這是否合理？這是肺癌的總體規劃嗎？

And the second question was Ultomiris. So you've now got the launch in MG and you've also got NMO coming. So can you remind us what your updated thinking is about how much you can convert over the combined Soliris, Ultomiris franchise over to Ultomiris by the time that Soliris faces loss of exclusivity in 2025? I think the conversion is about 30% now, but is the thinking that you can more than double this conversion in the next 3 years?

第二個問題是Ultomiris。因此，您現在已經在 MG 中推出了產品，並且您還推出了 NMO。那麼，您能否提醒我們您的最新想法是，當 Soliris 在 2025 年面臨失去排他性時，您可以將合併後的 Soliris、Ultomiris 特許經營權轉換為 Ultomiris 多少？我認為現在的轉化率約為 30%，但是否認為您可以在未來 3 年內將轉化率提高一倍以上？

Thanks, Jim.

謝謝，吉姆。

So the first question would be Susan, the second question, Marc, is about the rate of -- not the position, but switch from Soliris to Ultomiris by 2025. Susan, do you want to...

所以第一個問題是蘇珊，第二個問題是馬克，是關於 2025 年之前從 Soliris 切換到 Ultomiris 的速度。蘇珊，你想...

Yes. So just the design of the ORCHARD study, it's a platform-based Phase II study. It's not designed to be a pivotal study. And of course, in order to drive a pivotal trial design, we want to look at safety and efficacy data.

是的。所以只是 ORCHARD 研究的設計，它是一個基於平台的 II 期研究。它並非旨在成為一項關鍵研究。當然，為了推動關鍵的試驗設計，我們希望查看安全性和有效性數據。

I'll just reiterate what I said, we are planning to initiate a number of Phase III trials over the next 18 months, and we'll continue to evolve as data emerges from the proof-of-concept driving studies.

我只是重申我所說的話，我們計劃在未來 18 個月內啟動一些 III 期試驗，並且隨著概念驗證駕駛研究中數據的出現，我們將繼續發展。

So Jeff, I think your question was on the rate of conversion on myasthenia gravis, I assume. Let me provide just some reference on the rate of conversion in PNH is above 80%. The rate of conversion on atypical HUS is above 50%. So by 2025, this means 3 years after launch, in myasthenia gravis, we can expect somewhere closer to atypical HUS, I believe, in 3 years' time. And NMO, it's a bit hard to guess. But due to the excellent results that we have seen, we believe the conversion will also be relatively rapid.

所以傑夫，我想你的問題是關於重症肌無力的轉化率，我想。讓我提供一些關於 PNH 轉換率高於 80% 的參考。非典型 HUS 的轉化率高於 50%。所以到 2025 年，這意味著在推出 3 年後，在重症肌無力中，我們可以期待在 3 年後更接近非典型 HUS。而 NMO，這有點難以猜測。但是由於我們已經看到了出色的結果，我們相信轉換也會相對迅速。

Simon Baker. Go ahead, Simon.

西蒙·貝克。來吧，西蒙。

Two pipeline ones, if I may.

如果可以的話，有兩個管道。

Firstly, on adavosertib, which you've terminated. I'm assuming that was on tolerability grounds, but any color on that would be useful. And is that the end of what you want as a target? Because I noticed that Merck had disclosed another (inaudible) inhibitor that appears to have the slightly less aggressive structure than adavosertib?

首先，在您已終止的 adavosertib 上。我假設這是基於耐受性，但任何顏色都是有用的。這就是你想要的目標的結束嗎？因為我注意到默克公司披露了另一種（聽不清）抑製劑，其結構似乎比 adavosertib 的侵襲性略低？

And then secondly, on Fasenra. I see on clinical trials of last week that both RESOLUTE and ORCHID were moved back a year for primary completion. Is that just housekeeping or also a genuine delay there?

其次，關於法森拉。我在上週的臨床試驗中看到，RESOLUTE 和 ORCHID 都被推遲了一年完成初步完成。這只是家務還是那裡的真正延誤？

Thanks, Simon.

謝謝，西蒙。

Mene, do you want to take the first and last question? And...

梅內，你要回答第一個和最後一個問題嗎？和...

I mean, again, that's really due to delays through COVID and the Ukraine-Russia war. Nothing from a data perspective.

我的意思是，這實際上是由於 COVID 和烏克蘭-俄羅斯戰爭造成的延誤。從數據的角度來看什麼都沒有。

And Susan, adavosertib?

蘇珊，adavosertib？

So I think (inaudible) is -- remains an important target. The challenge for adavosertib is the combination of GI, diarrhea-inducing side effects as well as the combination of that with bone marrow toxicity. And the combination of those 2 together proves challenging.

所以我認為（聽不清）仍然是一個重要目標。 adavosertib 面臨的挑戰是胃腸道、腹瀉誘導副作用以及骨髓毒性的結合。這兩者的結合證明具有挑戰性。

So there's clear activity seen with the adavosertib including in some difficult-to-treat cancers like uterine, serous carcinoma. But when we look at the overall profile versus everything else that we've got in our portfolio and what we've made is a prioritization decision to make sure that we apply our resources on the products that we think have a greater transformative ability for the treatment of patients with cancer.

因此，adavosertib 具有明顯的活性，包括一些難以治療的癌症，如子宮癌、漿液性癌。但是，當我們查看整體概況與我們的產品組合中的其他所有內容時，我們所做的是一個優先級決定，以確保我們將我們的資源應用於我們認為具有更大變革能力的產品上癌症患者的治療。

Okay.

好的。

Michael Leuchten at UBS. Michael, over to you.

瑞銀的邁克爾·勒赫滕。邁克爾，交給你了。

And just going back to the increase in OpEx for this year, just trying to understand the timing. A lot of the pivotal data that would have suggested you should invest more in ADCs and other compounds you had earlier in the year. So what's changed in July to decide to spend $1 billion more this year in OpEx?

回到今年 OpEx 的增長，只是想了解時機。許多關鍵數據表明您應該在 ADC 和今年早些時候擁有的其他化合物上進行更多投資。那麼，今年 7 月決定在 OpEx 上增加 10 億美元的支出發生了什麼變化？

And then just going back to (inaudible) of the incremental revenues you now expect in the second half, how much of that is based on contracts that you have and how much of it depends on you successfully pushing the product more into, I guess, a commercial and non-government setting?

然後回到（聽不清）你現在預計下半年的增量收入，其中有多少是基於你擁有的合同，有多少取決於你成功地將產品推向更多，我猜，商業和非政府環境？

So the second question is about (inaudible) Iskra, do you want to take this?

所以第二個問題是關於（聽不清）火星報，你想接受這個嗎？

Yes. Let me start with that.

是的。讓我從那開始。

So the revenue is predicted now for the second half of the year, a combination of what you're saying. Many of that is coming from the contracts that I already agreed with many countries around the globe. But equally, as I mentioned, we are increasing the capacity as much as we can to be able to also supply and increase the supply for the patients that are not still covered with the existing contracts.

所以現在預測下半年的收入，結合你所說的。其中許多來自我已經與全球許多國家達成的合同。但同樣，正如我所提到的，我們正在盡可能地增加產能，以便能夠為現有合同尚未涵蓋的患者提供和增加供應。

Thanks, Iskra.

謝謝，火星報。

And maybe, Aradhana, you could take the other question? And also there's a question online about the clarifying total revenue guidance, so you could take the whole thing together.

也許，Aradhana，你可以回答另一個問題？還有一個關於澄清總收入指導的在線問題，所以你可以把整個事情放在一起。

Sure. Yes.

當然。是的。

So Michael, just to answer your question around OpEx. So there are a number of elements actually in OpEx. There's obviously increase in R&D and that's not just the ADC portfolio, which obviously is a big component of it. But it's really across board, and that includes further investments in rare diseases, further investments in BioPharma. As you know, we've done some licensing arrangements there as well, as well as continuing to invest behind Enhertu and Dato as well as our internal pipeline on ADC. So it's actually quite a large portfolio that we're investing behind in R&D.

所以邁克爾，只是為了回答你關於運營支出的問題。所以實際上在 OpEx 中有很多元素。研發明顯增加，而不僅僅是 ADC 產品組合，這顯然是其中的一個重要組成部分。但這確實是全面的，包括對罕見病的進一步投資，對生物製藥的進一步投資。如您所知，我們在那裡也做了一些許可安排，並繼續投資 Enhertu 和 Dato 以及我們在 ADC 上的內部管道。所以這實際上是我們在研發方面投資的相當大的投資組合。

The -- In addition, there's also SG&A, which we talked a little bit about the ungating of some of the spend on Evusheld relating to demand creation that we're doing. But at the same time, we also have several other launches. As you know, Saphnelo is still early, Tezspire, Fasenra as well as Breztri and on the oncology side, multiple new indications that we'll need to continue to build the market on behind HIMALAYA and TOPAZ. So hopefully, that addresses your question.

- 此外，還有 SG&A，我們談到了一些關於取消 Evusheld 上與我們正在做的需求創造相關的一些支出。但與此同時，我們還有其他幾項發布。如您所知， Saphnelo 仍處於早期階段，Tezspire、Fasenra 以及 Breztri 以及在腫瘤學方面，我們需要繼續在 HIMALAYA 和 TOPAZ 之後建立市場的多個新跡象。所以希望這能解決你的問題。

I think the second question that Pascal referred to was, I think there was a clarification on total revenue guidance and that is a low 20s increase in revenue. So just -- so that's clear.

我認為帕斯卡提到的第二個問題是，我認為對總收入指導進行了澄清，即收入增長 20 多歲。所以只是 - 這很清楚。

Thanks, Aradhana. So Luisa Hector, Berenberg. Luisa, over to you.

謝謝，阿拉達納。所以貝倫貝格的路易莎·赫克托。路易莎，交給你了。

A couple of questions.

幾個問題。

On Farxiga, I just wonder if you can give any more color on what we should be looking out for at ESC? Should we expect a benefit across all components of the composite endpoint? And how soon could this contribute to sales? And I wonder if you've actually stated when you expect generics in China, I heard all your comments about the phasing of LoE, but I just wondered specifically on China.

在 Farxiga 上，我只是想知道您是否可以對我們在 ESC 上應該注意的內容提供更多顏色？我們是否應該期望復合端點的所有組件都受益？這多久能促進銷售？我想知道你是否真的說過你在中國期待仿製藥，我聽到了你所有關於 LoE 分階段的評論，但我只是特別想知道中國。

And then second question for you, Pascal, because it's clear your confidence in the growth profile beyond 2025. Are there any areas in particular you would highlight where your internal projections are different from consensus? And perhaps just a comment on what you do factor in for pricing in that longer-term view?

然後是第二個問題，帕斯卡，因為很明顯您對 2025 年以後的增長狀況充滿信心。您是否會特別強調您的內部預測與共識不同的地方？也許只是對您在長期觀點中定價的因素的評論？

. So maybe I can start with this one and also clarify the $1 billion that Michael was mentioning before, I'm not sure where that comes from. But I mean, our guidance with expenses has been low to mid, and now it's mid to high. So you could potentially derive this, but you could also derive less than $1 billion.

.所以也許我可以從這個開始，並澄清邁克爾之前提到的 10 億美元，我不確定它來自哪裡。但我的意思是，我們對費用的指導從低到中，現在是中到高。所以你可能會得到這個，但你也可能得到不到 10 億美元。

Remember also in the guidance, we have reduced the other income. So it's not only an expense issue, it's also reducing other income in our guidance. And in terms of the increase of expenses, it's really linked to the products -- the portfolio we've discussed -- versus consensus we typically do not comment. What I can say is what are the products that we see as being big potential products and the first 2 will not surprise you. Enhertu and Dato-Dxd, we believe those 2 have very, very large potential for the many reasons we have described.

還要記住，在指導中，我們減少了其他收入。因此，這不僅是一個費用問題，而且還減少了我們指導中的其他收入。就費用的增加而言，它確實與產品有關——我們討論過的產品組合——而不是我們通常不發表評論的共識。我能說的是哪些產品是我們認為具有巨大潛力的產品，前兩個不會讓你感到驚訝。 Enhertu 和 Dato-Dxd，我們相信這兩個具有非常非常大的潛力，原因有很多。

Beyond that, in oncology, maybe I should ask Dave to comment in terms of what [CCL's] potential. And BioPharma, Ruud, you also would want to say a few words about the products you see as having big potential? Not necessarily versus consensus, but where we see the biggest potential.

除此之外，在腫瘤學方面，也許我應該請戴夫就 [CCL 的] 潛力發表評論。 BioPharma，Ruud，您也想對您認為具有巨大潛力的產品說幾句話嗎？不一定與共識相反，但我們看到了最大的潛力。

I mean, I think, Luisa, your question is 2025 and beyond, I think that to Pascal's point, and I've mentioned this before, the ADCs, certainly. I think secondly, we're beginning to get momentum and enthusiasm around the next wave of IO, which includes bispecifics, and I think that we'll see more on that to come.

我的意思是，我想，路易莎，你的問題是 2025 年及以後，我認為帕斯卡的觀點是，我之前已經提到過，當然是 ADC。我認為其次，我們開始在下一波 IO 中獲得動力和熱情，其中包括雙特異性，我認為我們會看到更多關於這方面的信息。

Additionally, I believe that the PARP-1 selective is something that, again, here has an early profile that gives me a lot of enthusiasm as Lynparza moves into exclusivity, and it's the first and only in this decade within the portfolio of oncology that goes there.

此外，我相信 PARP-1 選擇性是一種東西，這裡有一個早期的概況，隨著 Lynparza 進入排他性，它給了我很大的熱情，它是腫瘤學組合中的第一個也是唯一一個十年來那裡。

Those for me are the big highlights, and it's the combinations between IO and ADCs, where I really think that we've got the opportunity to do some important and differentiated clinical approaches.

對我來說，這些是最大的亮點，它是 IO 和 ADC 之間的組合，我真的認為我們有機會做一些重要的和差異化的臨床方法。

Okay. I will quickly comment regarding the BioPharma.

好的。我將很快就生物製藥發表評論。

I think in the short term, clearly, the trajectory of Farxiga is very promising. And I will also answer your question regarding the expectation in China. The loss of exclusivity is in 2023, but we don't expect a lot of impact instantly. We are expecting VBP in the course of 2024 if it happens, but it still has a substantial potential.

我認為在短期內，很明顯，法西加的發展軌跡非常有希望。我也會回答你關於對中國的期望的問題。排他性的喪失發生在 2023 年，但我們預計不會立即產生很大影響。如果它發生，我們預計在 2024 年會出現 VBP，但它仍然具有巨大的潛力。

Of course, the new portfolio products like Tezspire, Saphnelo and Breztri has a substantial potential. And then in the midterm, a product like eplontersen, already show good results in (inaudible). And then hopefully, in the future, also in cardiomyopathy are clear strong growth drivers for the business.

當然，Tezspire、Saphnelo 和 Breztri 等新產品組合具有巨大潛力。然後在中期，像 eplontersen 這樣的產品已經在（聽不清）顯示出良好的效果。然後希望，在未來，心肌病也是該業務的強勁增長動力。

And let me just start with the question around (inaudible) and Farxiga. So I can't comment on the results we'll present, but I don't think folks will be disappointed. And what I can maybe add is there'll be 2 high impact publications coming out at the same time, which hopefully will emphasize the quality of the data we're presenting.

讓我從圍繞（聽不清）和 Farxiga 的問題開始。所以我不能評論我們將呈現的結果，但我認為人們不會失望。我可以補充的是，將同時發布 2 篇高影響力的出版物，希望這將強調我們提供的數據的質量。

Maybe -- thanks, guys.

也許——謝謝，伙計們。

I mean, the last comment I will make, Luisa, is that one of the characteristics of our company is that we don't depend on 2 or 3 products and where you can say this one has enormous potential. We have many blockbuster potential already. We have more than 10 today, and we expect to have many more over the next few years. So there are a number of products that can be very big. And then there are others that are going to be smaller, but still blockbuster potential, more than $1 billion. So it's really adding up all these products that is going to drive the growth of AstraZeneca over the next 7, 8, 10 years.

我的意思是，路易莎，我要說的最後一條評論是，我們公司的特點之一是我們不依賴 2 或 3 種產品，您可以說這個產品具有巨大的潛力。我們已經有很多重磅炸彈的潛力。我們今天有 10 多個，我們預計未來幾年還會有更多。所以有很多產品可以非常大。還有其他一些規模較小但仍具有巨大潛力的產品，超過 10 億美元。因此，真正將所有這些產品加起來將推動阿斯利康在未來 7、8、10 年的增長。

Next question is Emily Field at Barclays, Emily?

下一個問題是艾米麗在巴克萊的艾米麗菲爾德，艾米麗？

Question. One on TROPION-Lung01 timing. I know you targeted first half '23. I believe Daiichi Sankyo this morning noted a potential for second half '22 with the caveat that's driven. Just your thoughts on the potential to see that top line data this year?

問題。一個關於 TROPION-Lung01 計時的。我知道你的目標是 23 年上半年。我相信 Daiichi Sankyo 今天早上註意到了 22 年下半年的潛力，並提出了警告。只是您對今年看到頂級數據的潛力的想法嗎？

A question on the myasthenia gravis launch for Ultomiris. Thanks for the color that 1/3 of the sales in complement naive, just curious on if you think you're winning patient share in that population versus (inaudible), which is off to a strong launch?

關於 Ultomiris 重症肌無力發射的問題。感謝 1/3 的銷售額補充天真的顏色，只是想知道您是否認為自己在該人群中贏得了患者份額，而不是（聽不清），這是一個強有力的發布？

And then Dave, in the prepared remarks, I believe you mentioned that you weren't seeing much contribution from DBO4 in the first half. Do you expect that there will be signing sales contribution ahead of the PDUFA date given the NCCN guidelines update?

然後戴夫，在準備好的評論中，我相信你提到你在上半年沒有看到 DBO4 的太多貢獻。鑑於 NCCN 指南更新，您是否預計會在 PDUFA 日期之前簽署銷售貢獻？

Thanks, Emily.

謝謝，艾米麗。

So Dave, do you want to take the TOPION question? And Marc, the other question? And we try to be short.

Dave，你想回答 TOPION 的問題嗎？馬克，另一個問題？我們盡量做空。

Yes. And maybe I can do the DBO4 and the TROPION both.

是的。也許我可以同時做 DBO4 和 TROPION。

So when Daiichi guides to second half '22, they're on their fiscal year, and so that goes into first quarter of next year. And when we guide to first half of '23, it's on a calendar year. So you can triangulate the quarter that we're both consistently speaking about.

因此，當 Daiichi 指導 22 年下半年時，他們正處於他們的財政年度，因此進入明年第一季度。當我們引導到 23 年上半年時，它是一個日曆年。因此，您可以對我們一直在談論的季度進行三角測量。

I think that within DB04. So Emily, I think that with the NCCN guidelines changing because of an overall survival benefit with the speed with which it did, and we already heard the discussion at ASCO, the discussion, not the presenter, talking about how HER2 low is something that she was considering for a patient that was in front of her. And then we know that there are many HER2 low patients that are already easy to identify, I do think that some level of non-promoted spontaneous use is likely to happen in advance of PDUFA. The exact amount of that, I think, is something that we'll just watch and see.

我認為在 DB04 內。所以艾米麗，我認為隨著 NCCN 指南的變化，因為整體生存受益和它的速度，我們已經聽到了 ASCO 的討論，討論，而不是演講者，談論 HER2 低是她正在考慮為她面前的一個病人。然後我們知道有很多 HER2 低的患者已經很容易識別，我確實認為在 PDUFA 之前可能會發生某種程度的非促進自發使用。我認為，確切的數量是我們將拭目以待的東西。

As expected with interaction of the new app therapeutic option, the estimates marketing as the space is expanding very rapidly. Has not been communicated by Argenx that seem to be taking many patients from IVIG and earlier line of therapies. We have launched Ultomiris at the end of April. And although it is early days, I think we are seeing that we are already gaining naive patients for about 1/3 of the of the initiation. We expect this to continue in the future.

正如新應用程序治療選項的交互所預期的那樣，估計營銷空間正在迅速擴大。 Argenx 尚未傳達似乎正在從 IVIG 和早期治療線中接收許多患者的信息。我們在 4 月底推出了 Ultomiris。雖然現在還處於早期階段，但我認為我們已經看到，在大約 1/3 的初始階段，我們已經獲得了天真的患者。我們預計這將在未來繼續。

So you remember that until the introduction of this recent introduction, Ultomiris, and (inaudible) Soliris was the only branded medicine in myasthenia gravis and was treating more severe forms of myasthenia gravis. So with Ultomiris, our mission will be to go down in severity and cover a larger group of patients. So early days, but a good start.

所以你記得在最近的介紹之前，Ultomiris 和（聽不清）Soliris 是重症肌無力的唯一品牌藥物，並且正在治療更嚴重的重症肌無力形式。因此，對於 Ultomiris，我們的任務將是降低嚴重程度並覆蓋更大的患者群體。這麼早，但是一個好的開始。

Thanks, Marc.

謝謝，馬克。

Matt Weston, Credit Suisse. Matt, over to you.

馬特韋斯頓，瑞士信貸。馬特，交給你了。

Two questions, if I can, please.

兩個問題，如果可以的話，請。

The first, coming back to operating costs. The new guidance on R&D is essentially trending towards $10 billion. Aradhana reiterated the low 20s percent of R&D as your target. But I'm mindful that consensus has $9 billion of spend and a 2.5 percentage point margin increase year-over-year for 2023. I don't want to draw you into '23 guidance, but can I just be clear that the message is pipeline success just as increased investment and that's what investors should be prepared for? And any color you can give us around that would be great.

首先，回到運營成本。新的研髮指導基本上趨向於 100 億美元。 Aradhana 重申了低 20% 的研發是你的目標。但我注意到，2023 年的共識是 90 億美元的支出和 2.5 個百分點的利潤率同比增長。我不想把你拉到 23 年的指導中，但我可以明確一點，信息是管道成功就像增加投資一樣，這就是投資者應該準備的？你可以給我們周圍的任何顏色都會很棒。

And then secondly, a question about mid-term margins. You commented about mid- to high 30s, but obviously, you've also highlighted how much the potential of the Daiichi Sankyo collaboration product could have to the future growth of Astra. And I just wonder how you see that impacting that margin number given that you book only a very modest amount of sales but 50% of earnings? So I would imagine it could easily push you over that high 30s if they were to achieve the peak sales that you seem to be hoping for?

其次，關於中期利潤率的問題。您評論了 30 多歲的中高水平，但顯然，您也強調了 Daiichi Sankyo 合作產品對 Astra 未來增長的潛力有多大。我只是想知道，鑑於您只預訂了非常少量的銷售額但收入的 50%，您如何看待這會影響該利潤率數字？所以我想如果他們要達到你似乎希望的最高銷售額，它可以很容易地把你推到 30 多歲？

Thanks. Matt. The 2 questions, so maybe Aradhana, you can cover the margin.

謝謝。馬特。這 2 個問題，所以也許 Aradhana，你可以填補空白。

On the -- the first point on the R&D spend, Matt, Aradhana said to you that the second half, we expect to have R&D expenses being consistent with first half. So if you do that, you don't get to 10. I mean, you're not that far, of course, but you're substantially below 10 if you do this math.

關於 - 關於研發支出的第一點，Matt，Aradhana 對你說，下半年，我們預計研發支出與上半年保持一致。所以如果你這樣做，你就不會達到 10。我的意思是，你當然沒有那麼遠，但是如果你做這個數學，你就會大大低於 10。

And in terms of the question as to whether this is justified by the pipeline, the answer is absolutely. Yes, otherwise, we would not spend it. We have really, a growing -- a rapidly growing pipeline, and we need to support it. If you actually think about a product like Enhertu and a product like Dato-Dxd, taking them to their full potential requires a pretty large program and a lot of investment, and this is something that we have become more and more convinced we need to do.

至於管道是否證明這是合理的問題，答案是絕對的。是的，否則，我們不會花掉它。我們確實有一個不斷增長的 - 一個快速增長的管道，我們需要支持它。如果你真的想到像 Enhertu 這樣的產品和像 Dato-Dxd 這樣的產品，要充分發揮它們的潛力需要一個相當大的計劃和大量的投資，這是我們越來越確信我們需要做的事情.

And then beyond those 2, we have got a number of products certainly (inaudible) requires investment. And we really want to play to win. We want to make sure that every one of our products with potential is totally supported too, so we expand them and maximize them.

然後除了這 2 個之外，我們還有一些產品肯定（聽不清）需要投資。我們真的很想贏球。我們希望確保我們每一款具有潛力的產品也得到完全支持，因此我們將它們擴展並最大化它們。

As far as the margin, maybe Aradhana, you want to cover this? But we need to keep in mind that we also have Tezspire, we have Lynparza, we have products that are not necessarily always helping with the margin near term.

至於邊緣，也許是阿拉達納，你想覆蓋這個嗎？但我們需要記住，我們也有 Tezspire，我們有 Lynparza，我們的產品不一定總是在短期內幫助提高利潤率。

Yes. I think, again, our ambition remains the same in terms of margin. But as you can imagine, it's always a balance between shorter-term margin and longer-term growth. And as Pascal said, we're playing to win here, and we continue to invest behind the product.

是的。我認為，在利潤方面，我們的野心仍然是一樣的。但正如您可以想像的那樣，它始終是短期利潤率和長期增長之間的平衡。正如帕斯卡所說，我們在這里為勝利而戰，我們將繼續投資於產品背後。

The specific question you had was around the Daiichi product and the partnership with -- on Enhertu and Dato. And yes, we have high hopes and high ambitions for those. But also note that we do pay our fair share of R&D and SG&A expenses. So while on the revenue line, we may not count as product revenues, counted as collaboration revenue, our profit share, we are contributing our fair share of expenses. So we really need to look at sort of an operating profit line there rather than the sort of the margins that are employed.

您遇到的具體問題是關於 Daiichi 產品以及與 Enhertu 和 Dato 的合作關係。是的，我們對這些寄予厚望和雄心壯志。但也請注意，我們確實支付了研發和 SG&A 費用的公平份額。因此，雖然在收入線上，我們可能不會算作產品收入，算作合作收入，我們的利潤份額，我們正在貢獻我們公平的費用份額。所以我們真的需要看看那裡的營業利潤線，而不是所使用的利潤率。

And again, we're focused on cash flow and improving our operating profit from a dollar standpoint and a margin standpoint.

再一次，我們專注於現金流，從美元的角度和利潤率的角度提高我們的營業利潤。

I mean, these 2 products that can be very large, these 2 ADCs, they will drive tremendous growth post '25. And until '25, they will drive growth, but they will also drive a substantial investment. These studies in oncology, they are -- they tend to take time. They're expensive, and they are quite large. So that's really what you have to keep in mind when you look at the margin.

我的意思是，這兩種可能非常大的產品，這兩種 ADC，它們將在 25 年後推動巨大的增長。在 25 年之前，它們將推動增長，但它們也將推動大量投資。這些腫瘤學研究是——它們往往需要時間。它們很貴，而且很大。因此，當您查看邊距時，這確實是您必須牢記的。

But having said that, I'd just like to repeat what I said before, we haven't actually changed our ambition to improve our margin to mid to high single 30s, mid to high 30s in the mid to long-term horizon. So nothing has changed there as far as our profitability ambition. It's just that we want to make sure that we do this, and at the same time, we don't improve margin at the expense of long-term sustainable works.

但是話雖如此，我還是想重複我之前說過的話，我們實際上並沒有改變我們的目標，即在中長期範圍內將利潤率提高到中高單 30 年代、中高 30 年代。因此，就我們的盈利目標而言，那裡沒有任何改變。只是我們想確保我們這樣做，同時，我們不會以犧牲長期可持續工作為代價來提高利潤率。

Emmanuel Papadakis? Yes, go ahead, Emmanuel.

伊曼紐爾·帕帕達基斯？是的，繼續，伊曼紐爾。

Sorry, okay. Perhaps I take a question on capivasertib ahead of the CAPItello291 data due in the second half of the year. So just your degree of optimism, Susan, on probability success in light of action and given a pretty mixed history of the glass? And then a couple of follow-ups.

對不起，好吧。也許我會在下半年發布 CAPItello291 數據之前對 capivasertib 提出一個問題。那麼，蘇珊，你對行動成功概率的樂觀程度以及考慮到玻璃的複雜歷史？然後是一些後續行動。

And [Jose], perhaps you could just give us a bit of color on where you think you are in terms of second-line metastatic share conversion from the current standard of care TDM-1?

還有 [Jose]，也許您可以給我們一些顏色，說明您認為您在當前護理標準 TDM-1 的二線轉移性份額轉換方面處於什麼位置？

And then Evusheld, you've mentioned several times it's retained efficacy, but I think it's pretty clear from recent publications that tozorakimab has at least -- has almost completely lost efficacy against the BA subvariants. So is there any contingency built into the contracts you're signing around returns or cancellations for potential complete loss of efficacy, which seems like a pretty high risk?

然後是 Evusheld，你已經多次提到它保留了療效，但我認為從最近的出版物中可以清楚地看出，tozorakimab 至少 - 對 BA 子變體幾乎完全失去了療效。那麼，您簽署的合同中是否存在任何意外情況，以應對可能完全喪失功效的退貨或取消，這似乎是一個相當高的風險？

So maybe what we could do is, Susan, you will cover the other question in a minute.

所以也許我們可以做的是，蘇珊，你會在一分鐘內討論另一個問題。

But Mene, do you want to cover the Evusheld from sort of an efficacy viewpoint and what we are working on? And then Iskra, you could cover the question about contract?

但是梅內，你想從某種功效的角度來報導 Evusheld 以及我們正在做的事情嗎？然後是《火星報》，你可以回答關於合同的問題嗎？

Yes, it's a great question around the antibodies. I think we were very specific in terms of always having 2 antibodies in Evusheld specifically for the reason that you're asking. So we have seen, obviously, some reduction in activity or one or other antibodies brush when you put them together, the efficacy remains intact and robust.

是的，這是一個關於抗體的好問題。我認為我們非常具體地在 Evusheld 中始終擁有 2 種抗體，特別是出於您所問的原因。因此，我們顯然已經看到，當您將它們放在一起時，活性有所降低或一種或其他抗體刷刷，功效保持完整和強大。

And I think you also need to be careful not to be confusing a decrease in neutralize -- in vitro neutralization, pseudovirus assays with a decrease in efficacy because that doesn't necessarily translate. Because you don't know what the level of nuclearizing activity in vitro is to get it.

而且我認為你還需要小心不要混淆中和的減少 - 體外中和，假病毒測定與功效的降低，因為這並不一定會轉化。因為你不知道體外核化活動的水平是多少才能得到它。

Iskra said in the real world studies that we're seeing with current variants, the efficacy is remaining very robust across all the variants. It's because we have 2 antibodies, I think we're in reasonably good shape, and we are never going to get resistance, but I think we're reasonably well protected. But of course now, the next generation of antibodies that we acquired are going to enable us to find additional binders that will further protect us from those resistant variants if they occur.

Iskra 說，在我們看到的當前變體的現實世界研究中，所有變體的功效仍然非常強大。這是因為我們有 2 種抗體，我認為我們的狀態相當不錯，而且我們永遠不會產生抗藥性，但我認為我們受到了相當好的保護。但當然現在，我們獲得的下一代抗體將使我們能夠找到額外的結合劑，如果它們發生，這些結合劑將進一步保護我們免受這些耐藥變異的侵害。

Mene, before you cover the contract question, maybe something -- it's worth reminding everybody is when we talk about the efficacy of Evusheld, the numbers you've heard are efficacy against one symptom. We're not talking about efficacy against severe disease or whatever, we're talking about efficacy against one symptom. So it's a tremendous level of efficacy that we have today, and then real-world evidence is demonstrating it's still there.

梅內，在你談到合同問題之前，也許是什麼——值得提醒大家的是，當我們談論 Evusheld 的功效時，你聽到的數字是針對一種症狀的功效。我們不是在談論對抗嚴重疾病或其他什麼的功效，我們談論的是對抗一種症狀的功效。所以這是我們今天擁有的巨大功效，然後現實世界的證據表明它仍然存在。

What that means is we protect people not against severe disease, we protect them against being symptomatic. So it's a fantastic efficacy.

這意味著我們保護人們免受嚴重疾病的侵害，我們保護他們免於出現症狀。所以這是一個奇妙的功效。

(inaudible) That's like a running nose, a cough, a fever. I mean it's small ....

（聽不清）就像流鼻涕、咳嗽、發燒一樣。我的意思是它很小....

(inaudible) Something, runny nose or cough. So I mean, it's really a very impressive efficacy level.

（聽不清）某事，流鼻涕或咳嗽。所以我的意思是，這確實是一個非常令人印象深刻的功效水平。

Iskra?

火星？

And I think it's really worth highlighting again that we really believe that the activity will not be lost in the new variant. And I think that just to build on the (inaudible) point, we do see a different level of efficacy of different antibodies in the different variants. But it is true that one or the other are really keeping the strong efficacy.

而且我認為值得再次強調的是，我們真的相信該活動不會在新變體中丟失。而且我認為只是建立在（聽不清）點的基礎上，我們確實看到了不同變體中不同抗體的不同功效水平。但確實，其中一個或另一個確實保持著強大的功效。

Therefore, I mean -- and we are working with the government and the relevant healthcare stakeholders being transparent on that. And I do believe that we will find a way even in case the resistance will happen to make sure that we deliver what will be needed to protect the patients and equally to find a way how to make sure that governments will be protected in a way given the unpredictability of the COVID-19 environment.

因此，我的意思是——我們正在與政府和相關的醫療保健利益相關者合作，對此保持透明。我確實相信，即使發生抵抗，我們也會找到一種方法，以確保我們提供保護患者所需的東西，並同樣找到一種方法來確保政府以既定的方式受到保護COVID-19 環境的不可預測性。

I think it's also fair to say that from the vaccine onwards, I think we are all working in the environment that is extremely volatile and dynamic, and that we are all taking a different level of risks moving forward, making sure that we have deliver medicines, both vaccines and antibodies, that can continue to protect the patients and prevent -- protect them from the COVID-19.

我認為公平地說，從疫苗開始，我認為我們都在極其不穩定和動態的環境中工作，並且我們都在向前邁進不同程度的風險，以確保我們能夠提供藥物，疫苗和抗體，可以繼續保護患者並預防——保護他們免受 COVID-19 的侵害。

Susan -- Thanks Iskra.

蘇珊——謝謝火星報。

So in terms of the development of (inaudible) we were very careful to make sure that we develop the right dose and schedule. So the intimate dosing schedule 4 days on, 3 days off, is something that optimizes the tolerability and minimizes the discontinuation rate, which I think is an important feature of the design.

因此，就（聽不清）的發展而言，我們非常小心地確保我們制定了正確的劑量和時間表。因此，4天休息3天的親密給藥計劃可以優化耐受性並最大限度地減少停藥率，我認為這是設計的一個重要特徵。

And then the second thing that builds confidence is, of course, the data from Fraction, which I highlighted in the presentation. 55% of patients have the activated pathway PI3 kinase/AKT/PTEN loss. And in that group, we saw really impressive improvement in not just PFS, but in overall survival with a hazard ratio of 0.46 for overall survival. So we do Phase III trials in order to confirm the activity we've seen in Phase II, but we have a good level of confidence in the importance of this pathway and in the ability of this molecule to inhibit the pathway well and to have that done in a tolerable way.

然後，建立信心的第二件事當然是來自 Fraction 的數據，我在演示文稿中強調了這一點。 55% 的患者有激活途徑 PI3 激酶/AKT/PTEN 丟失。在該組中，我們不僅在 PFS 方面看到了令人印象深刻的改善，而且在總體存活率方面也有顯著改善，總體存活率的風險比為 0.46。因此，我們進行 III 期試驗以確認我們在 II 期看到的活性，但我們對這條途徑的重要性以及這種分子能夠很好地抑制途徑並擁有它的能力充滿信心以可容忍的方式完成。

I'm just going to hand over to Dave now to talk about the Enhertu question.

我現在要請戴夫談談 Enhertu 的問題。

Yes. So Emmanuel, on Enhertu, we've seen really brisk conversion in second line just 2 months after approval. We now have 35% share of second line Enhertu positive. Just to put into perspective, we saw Kadcyla, TDM-1 a year ago, probably in 45% to 50% use. And so the majority of that 35% use that we're seeing right now in second line is coming at the expense of TDM-1. We do see some reduction in some other areas.

是的。因此，在 Enhertu 上，Emmanuel 在獲得批准後僅 2 個月就在二線看到了非常快速的轉換。我們現在在二線 Enhertu 中佔有 35% 的份額。換個角度來看，一年前我們看到了 Kadcyla，TDM-1，可能有 45% 到 50% 的使用率。因此，我們現在在二線看到的 35% 的使用中的大部分都是以 TDM-1 為代價的。我們確實看到其他一些領域有所減少。

I'd also note that we also continue to see use in third line plus for those don't see, obviously, or who haven't had an opportunity to be able to yet get Enhertu in the second line. So I'm proud of the work that the AZ and DS teams are doing just in 2 months after the launch.

我還要指出，我們還繼續看到在第三線中的使用以及對於那些看不到的人，顯然，或者還沒有機會在第二線中獲得 Enhertu 的人。因此，我為 AZ 和 DS 團隊在發布後僅 2 個月內所做的工作感到自豪。

Thanks, Dave.

謝謝，戴夫。

So we are over time, but we appreciate that you are very interested, and we love your questions, and they are great questions. We also want to respect your time, so we'll take 2 or 3 more questions and then close the call.

所以我們隨著時間的推移，但我們感謝您非常感興趣，我們喜歡您的問題，它們是很好的問題。我們也希望尊重您的時間，因此我們會再回答 2 或 3 個問題，然後結束通話。

Viktor Sundberg, Nordea. Viktor, over to you.

維克多·桑德伯格，北歐。維克托，交給你了。

One question on MEDI5752, your PD-1 CTL-4 bispecific that you presented at ASCO. I think it was clear that the 1,500-milligram cohort was too toxic, but also on the 750 milligram, the discussant commented that the toxicity looks fairly similar to ipi/nivo alone. So my question is if you agree with that assessment? And if the 500-milligram dose is the way to go forward for that program? And if you think efficacy will be enough of that lower dose?

關於 MEDI5752 的一個問題，您在 ASCO 上提出的 PD-1 CTL-4 雙特異性。我認為很明顯 1,500 毫克的隊列毒性太大，但在 750 毫克的情況下，討論者評論說毒性看起來與單獨的 ipi/nivo 非常相似。所以我的問題是你是否同意這個評估？如果 500 毫克的劑量是該計劃的前進方向？如果您認為較低劑量的療效就足夠了？

And perhaps a quick second question as well on HER2 low just quickly. So we know that HER2 low expression is less common in (inaudible) negative patients. But any data you have seen it's also lower in earlier lines of treatment, irrespective of [HER] status compared to later lines of treatment just for modeling purposes?

也許還有一個關於 HER2 低的快速第二個問題。所以我們知道 HER2 低表達在（聽不清）陰性患者中不太常見。但是，與僅出於建模目的的後期治療相比，無論 [HER] 狀態如何，您所看到的任何數據在早期治療中也較低？

Susan, do you want to cover this?

蘇珊，你想報導這個嗎？

Yes, sure. So the 5752. First of all, at doses of about 500 and 750 milligrams, if you look at the effect on T-cell proliferation rate, you are in the range of increase you would expect to get from around a 10 mg per kg dose of ipilimumab or tremelimumab. And we presented that with some of the data at AACR.

是的，當然。所以是 5752。首先，在大約 500 和 750 毫克的劑量下，如果你觀察對 T 細胞增殖率的影響，你會在每公斤劑量大約 10 毫克的預期增加範圍內易普利姆瑪或曲美木單抗。我們在 AACR 上展示了一些數據。

In terms of the tolerability, we're obviously looking at the discontinuation rate, and we'll continue to evaluate that both 750 and 500 milligrams. We will be presenting some more data in combination with chemotherapy in non-small cell lung cancer setting at the World Congress on Lung Cancer. So look for that as well. But we look at the totality of the data. And overall, we're encouraged profile that we see that we can get a good tolerability profile with improved efficacy compared with what you'd expect with a PD-1 agent alone.

就耐受性而言，我們顯然正在關注停藥率，我們將繼續評估 750 和 500 毫克。我們將在世界肺癌大會上展示更多與非小細胞肺癌化療相結合的數據。所以也要找那個。但我們看的是數據的整體。總體而言，我們感到鼓舞的是，我們看到與您對單獨使用 PD-1 藥物的預期相比，我們可以獲得良好的耐受性並提高療效。

And in terms of HER2 low, I don't see a real shift in the HER2 low prevalence between early and late line.

就 HER2 低而言，我沒有看到早期和晚期之間 HER2 低患病率的真正轉變。

Thanks, Susan. Peter Welford, Jefferies.

謝謝，蘇珊。彼得韋爾福德，傑富瑞。

Just 2 quick ones.

只有2個快速的。

Firstly, just the comment on other operating income and the comments you made with regards to second half. I'm curious, does this mark at the end now of the sort of serious portfolio optimization that we're seeing from AstraZeneca? And should we now envisage, therefore, an end to these profits? Or is it more just this particular year given macroeconomic challenges, management's current focus that there hasn't been the same degree, but we should not necessarily assume that's going to be the case in the future years.

首先，只是對其他營業收入的評論以及您對下半年的評論。我很好奇，這是否標誌著我們從阿斯利康看到的那種嚴肅的投資組合優化的結束？因此，我們現在是否應該設想結束這些利潤？或者考慮到宏觀經濟挑戰，管理層目前關注的重點是沒有相同程度，但我們不一定假設未來幾年會出現這種情況。

And then secondly, just coming back to the SG&A. Just curious, you've talked in the past about the fact the years of investing more and more in China are now over. Just curious if you can update us on your thoughts there? Are you actually now taking cost out of China? Or how should we think about investment in China when we think about the SG&A trend?

其次，回到 SG&A。只是好奇，您過去曾說過，在中國越來越多的投資已經結束。只是好奇你是否可以在那裡更新你的想法？你現在真的把成本從中國轉移出去了嗎？或者當我們考慮SG&A趨勢時，我們應該如何考慮在中國的投資？

Maybe I can cover quickly what I say. Because I always describe what we've done is sort of pruning the tree, right? I mean, and basically the divesting products that would be better managed by someone else than by us and someone else could create value. So we've done a lot of this. There's less today, of course. And basically, now we are trying to grow new branches to the street to make it a beautiful tree with launching of new products.

也許我可以快速涵蓋我所說的話。因為我總是描述我們所做的就是修剪樹，對吧？我的意思是，基本上由其他人比我們和其他人更好地管理的剝離產品可以創造價值。所以我們已經做了很多。今天當然少了。基本上，現在我們正在嘗試在街道上種植新的樹枝，使其成為一棵美麗的樹，並推出新產品。

But it doesn't mean that it's finished. I mean, we'll basically manage that as we go, but there's definitely less older products to divest and less, less other income moving forward. So our intent is really to focus on our products, our new products grow them and develop the pipeline now.

但這並不意味著它已經完成。我的意思是，我們基本上會在進行過程中進行管理，但是要剝離的舊產品肯定會減少，未來的其他收入也會減少。因此，我們的意圖是真正專注於我們的產品，我們的新產品現在正在發展它們並開發管道。

Aradhana?

阿拉達納？

Yes. And I think the second question was around China and whether we're investing more in SG&A in China.

是的。我認為第二個問題是關於中國的，以及我們是否在中國加大對 SG&A 的投資。

Clearly, it's been a tremendous growth journey in China over the last several years. As you know, the government and pricing policies have put the growth there under pressure. That being said, we continue to invest in new products. And hopefully, the new product launches will drive that growth. We are managing our cost base in China in proportion to the revenue decline that we see. And again, we'll continue to manage that while investing in innovation.

顯然，在過去的幾年裡，這在中國是一段巨大的增長之旅。如您所知，政府和定價政策使那裡的增長面臨壓力。話雖如此，我們繼續投資於新產品。希望新產品的推出將推動這一增長。我們正在根據我們看到的收入下降比例來管理我們在中國的成本基礎。同樣，我們將在投資創新的同時繼續管理這一點。

Thanks, Aradhana.

謝謝，阿拉達納。

So we take the last question. Seamus Fernandez, Guggenheim. Seamus, over to you.

所以我們回答最後一個問題。西莫斯費爾南德斯，古根海姆。西莫，交給你了。

Pascal, and maybe you can be noted for horticultural comparisons as well.

帕斯卡，也許你也可以因園藝比較而聞名。

But the dynamics, I guess, around Dato. One quick question there. Maybe you guys can just help us understand, when you look at the data, Dave, you said you would hope that it would potentially replace late-line chemotherapy, but it's also being studied in combination with platinum-based chemotherapy. So is it your expectation that we will continue to see platinum-based chemotherapy as part of these regimens? Or is it possible that, that could be eliminated from the regimens going forward?

但我猜想，在拿督周圍的動態。一個快速的問題。也許你們可以幫助我們理解，當你查看數據時，戴夫，你說你希望它有可能取代晚期化療，但它也在與鉑類化療聯合研究。那麼您是否期望我們將繼續將基於鉑的化學療法視為這些方案的一部分？或者有沒有可能，這可以從未來的治療方案中消除？

And then secondly, just very quickly, on the COVID antibody approaches, just hoping you guys could give us a little color on whether or not the regulatory environment is changing such that COVID antibodies can actually come to market almost in the way that flu vaccines are reapproved over time? Just hoping to understand that context a little bit better.

其次，很快，關於 COVID 抗體的方法，只是希望你們能給我們一點顏色，了解監管環境是否正在發生變化，以便 COVID 抗體實際上可以像流感疫苗一樣進入市場隨著時間的推移重新批准？只是希望能更好地理解這種情況。

Thanks very much. So that's the first one, Susan, (inaudible) and the second one.

非常感謝。這是第一個，蘇珊，（聽不清）和第二個。

So the data that we'll present with the TROPION-Lung02 at the World Congress on Lung Cancer looks at the combination both with the double of Dato-Dxd plus pembro as well as the combination with platinum-based chemotherapy.

因此，我們將在世界肺癌大會上與 TROPION-Lung02 一起展示的數據著眼於與雙倍的 Dato-Dxd 加 pembro 的組合以及與基於鉑的化學療法的組合。

So I do think that it's probably going to depend a little bit on how patients present and what physicians are wanting to achieve. So those patients with bulky disease that want to achieve rapid and durable responses, there's a choice there, but you'll see the data at World Congress and Lung Cancer as it comes to.

所以我確實認為這可能在某種程度上取決於患者的表現方式以及醫生想要達到的目標。所以那些想要獲得快速和持久反應的大塊疾病患者，那裡有一個選擇，但你會看到世界大會和肺癌的數據。

Yes. I mean, I think the only thing that I'd add, and Seamus, you're pointing out that I sort of talk about the first sequence, I think, that the first step is replacing some of this late-line systemic chemotherapy. In terms of what's possible as we move into earlier lines, I think that obviously, both platinum and PEM are utilized here. And so one of the important clinical questions is the one that you're asking, which is, would we be able to replace both or just one of those? And they've got very different on a tolerability and number of cycles considerations. So those are the kinds of things we'll be answering in the program as the Phase IIIs in the frontline get underway.

是的。我的意思是，我想我唯一要補充的是，Seamus，你指出我有點談論第一個序列，我認為，第一步是替換一些晚期全身化療。就我們進入早期生產線的可能性而言，我認為很明顯，這裡使用了鉑金和 PEM。因此，重要的臨床問題之一就是您要問的問題，即我們能否同時替換這兩者或僅替換其中之一？他們在耐受性和循環次數方面有很大不同。因此，隨著前線第三階段的進行，我們將在計劃中回答這些問題。

Relatively easy came to you. So it's tempting to continue using it.

比較容易來找你。所以很想繼續使用它。

Mene, do you want to cover -- or Iskra, do you want to comment a bit on that?

Mene，你想報導——還是 Iskra，你想評論一下嗎？

I think it's a good question, and I can say that we would be hopeful to see the regulators taking the approach, the COVID-19 medicines, both on vaccine and antibodies, in the same way as they are doing for the flu. That would definitely accelerate and ease the way of the new updated vaccines and [monoclonals] for the new variants coming to the patients.

我認為這是一個很好的問題，我可以說我們希望看到監管機構採取這種方法，即 COVID-19 藥物，包括疫苗和抗體，就像他們對流感所做的那樣。這肯定會加速和簡化新的更新疫苗和 [單克隆] 的方式，以便為患者提供新的變體。

It's still not the case, but I'm sure you're aware that there are many discussions between the regulators and an equally discussions -- between the regulators and the manufacturers in the industry how to accelerate and optimize that process to be able to be -- to continue to be agile and flexible when it comes to bringing the medicines against COVID to the patients.

情況仍然不是這樣，但我相信你知道監管機構之間有很多討論，而且監管機構和行業製造商之間也有同樣的討論——如何加速和優化這個過程，以便能夠- 在將針對 COVID 的藥物帶給患者時，繼續保持敏捷和靈活。

Thanks, Iskra. So we'll close here. Thank you so much for your great interest, and I wish you all a good day and a good weekend. Thank you.

謝謝，火星報。所以我們會在這里關閉。非常感謝大家的關注，祝大家有個美好的一天，一個愉快的周末。謝謝你。