AstraZeneca PLC (AZN) 2021 Q3 法說會逐字稿

Good day. Welcome, ladies and gentlemen to the AstraZeneca's Year-to-date and Q3 Results 2021 Conference Call and Webcast for Investors and Analysts.

再會。女士們，先生們，歡迎參加阿斯利康 2021 年年初至今和第三季度業績電話會議以及面向投資者和分析師的網絡直播。

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.

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。

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.

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。

Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements. Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this conference call and webcast.

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。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。

(Operator Instructions) And with that, I will now hand you over to the company.

（操作員說明）然後，我現在將您交給公司。

Thank you, and good afternoon, everyone. I'm Chris Sheldon, Head of Investor Relations at AstraZeneca I'm pleased to welcome you to AstraZeneca's Third Quarter 2021 Conference Call. All materials presented today are available on our website.

謝謝大家，大家下午好。我是阿斯利康投資者關係主管 Chris Sheldon，我很高興歡迎您參加阿斯利康 2021 年第三季度電話會議。今天介紹的所有材料都可以在我們的網站上找到。

Slide 2 has the usual Safe Harbor statements. We will be making comments on our performance using constant exchange rates, or CER, core financial numbers and other non-GAAP measures, including total revenue, excluding the COVID-19 vaccine for pandemic use, as well as the impact of the pandemic vaccine on EPS. Our non-GAAP to GAAP reconciliation is contained within the results. Numbers used are in million U.S. dollars and for the first 9 months of 2021, unless otherwise stated.

幻燈片 2 有通常的安全港聲明。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，包括總收入，不包括用於大流行的 COVID-19 疫苗，以及大流行疫苗對每股收益。我們的非 GAAP 與 GAAP 對賬包含在結果中。除非另有說明，否則使用的數字為 2021 年前 9 個月的百萬美元。

Please advance to Slide 3. This slide shows today's speakers from our senior executive team. In a moment, I'll hand over to our CEO, Pascal Soriot, to begin.

請前進到幻燈片 3。這張幻燈片展示了我們高級管理團隊今天的演講者。稍後，我將由我們的首席執行官 Pascal Soriot 開始。

Please turn to Slide 4. (Operator Instructions)

請轉到幻燈片 4。（操作員說明）

Please advance to Slide 5. And with that, please, Pascal, over to you.

請轉到第 5 張幻燈片。Pascal 先生，請交給您。

Thank you, Chris, and hello, everyone. The third quarter of 2021 was an important milestone for our company with the addition of our Alexion colleagues. Alexion has been the remarkable diversified rare disease portfolio with significant growth opportunity. And a great part of this success is due to the talented team globally and very much -- I very much look forward to seeing all we can accomplish together. With the inclusion of Alexion from day 21st of July, we saw total revenue for the year-to-date of over $25 billion, an increase of 28%.

謝謝你，克里斯，大家好。隨著 Alexion 同事的加入，2021 年第三季度對我們公司來說是一個重要的里程碑。 Alexion 一直是具有顯著增長機會的多元化罕見病產品組合。這一成功的很大一部分歸功於全球才華橫溢的團隊，而且非常 - 我非常期待看到我們能夠共同完成的一切。從 7 月 21 日開始，隨著 Alexion 的加入，我們看到今年迄今為止的總收入超過 250 億美元，增長了 28%。

If you move to Slide 6, if you don't mind. Yes, thank you. The revenues, excluding the COVID-19 vaccine for pandemic use grew at 17%. The breadth of our now expanded portfolio allows us to continue to deliver on our growth ambition in the face of ongoing industry-wide pressures related to effects of COVID-19, which is still having an impact on patients visiting doctors or going to hospital.

如果您不介意，請移至幻燈片 6。是的，謝謝。不包括用於大流行的 COVID-19 疫苗的收入增長了 17%。面對與 COVID-19 影響相關的全行業持續壓力，我們現在擴大的產品組合的廣度使我們能夠繼續實現我們的增長雄心，這仍然對就診或去醫院的患者產生影響。

Total revenue in the quarter came very close to $10 billion, $9.9 billion precisely, a remarkable milestone, which, of course, was aided by our COVID-19 vaccine sales. But still, excluding the vaccine, we experienced tremendous growth. The core EPS of $3.59 is up 23% over prior year. and excluding the vaccine, the growth is 17%, reflecting continued leverage in our business.

本季度的總收入非常接近 100 億美元，準確地說是 99 億美元，這是一個了不起的里程碑，當然，這得益於我們的 COVID-19 疫苗銷售。但是，不包括疫苗，我們仍然經歷了巨大的增長。核心每股收益為 3.59 美元，比去年同期增長 23%。不包括疫苗，增長率為 17%，反映了我們業務的持續槓桿作用。

As a reminder, our vaccine has been supplied at no profit, and therefore, the vaccine sales year-to-date delivered no profit. Operating expenses growth in the quarter reflects in part the costs associated with the vaccine, the integration of Alexion and most importantly, our continued investment in our strategy to sustain an industry-leading pipeline and support our recent launches. We will now progressively transition our vaccine to for-profit, of course, but our price will ensure the vaccine is affordable for low- and middle-income countries. And therefore, the profit will remain limited.

提醒一下，我們的疫苗一直沒有盈利，因此，年初至今的疫苗銷售沒有盈利。本季度的運營費用增長部分反映了與疫苗相關的成本、Alexion 的整合，最重要的是，我們對維持行業領先管道和支持我們最近推出的戰略的持續投資。當然，我們現在將逐步將我們的疫苗轉變為營利性疫苗，但我們的價格將確保低收入和中等收入國家能夠負擔得起疫苗。因此，利潤將仍然有限。

We've updated our full year revenue guidance to reflect the contribution of our COVID-19 medicines in the fourth quarter. The great majority of our COVID-19 sales in Q4 will remain pandemic sales at no profit. Therefore, the Q4 profit arising from our vaccine sales will remain quite limited and will be offset by the investment -- the limited investment in our long-acting antibody combination, AZD7442. There's a limited investment that we need to do ourselves that is not covered by contracts we have with government. But essentially, the limited profit from the vaccine is offset by limited cost of the AZD7442 development. And overall, the COVID medicines will not contribute to profit in 2021.

我們更新了全年收入指引，以反映我們的 COVID-19藥物在第四季度的貢獻。我們在第四季度的大部分 COVID-19 銷售將保持無利潤的大流行銷售。因此，我們的疫苗銷售產生的第四季度利潤將仍然非常有限，並將被投資——我們的長效抗體組合 AZD7442 的有限投資所抵消。我們需要自己做的有限投資不在我們與政府簽訂的合同範圍內。但基本上，疫苗的有限利潤被 AZD7442 開發的有限成本所抵消。總體而言，COVID 藥物將不會在 2021 年為利潤做出貢獻。

So it's important to remember that the EPS guidance that we gave reflects the performance of the underlying business being the so-called, "old AZ plus Alexion." So it's a new AZ with Alexion, but excluding the COVID assets. Aradhana will provide additional detail on these important updates later in the presentation.

因此，重要的是要記住，我們給出的 EPS 指導反映了所謂的“老 AZ 加 Alexion”的基礎業務的表現。所以這是一個帶有 Alexion 的新 AZ，但不包括 COVID 資產。 Aradhana 將在演示文稿的稍後部分提供有關這些重要更新的更多詳細信息。

All of our business area of franchises are doing well. We demonstrated broad-based, double-digit growth with oncology growing at 16%, and in biopharmaceutical, CVRM growing at 10%, respiratory and immunology at 12%. For rare disease, the total revenue was $1.3 billion with year-to-date growth not meaningful due to the limit of the reporting period, but in line with our expectations. And for Q3, it's important to remember, we didn't have a full Q3 as far as Alexion is concerned. So we didn't have the full extent of sales, but also not the full extent of R&D spend and other costs.

我們所有的特許經營業務領域都做得很好。我們展示了基礎廣泛的兩位數增長，腫瘤學增長了 16%，生物製藥學的 CVRM 增長了 10%，呼吸和免疫學增長了 12%。對於罕見病，總收入為 13 億美元，由於報告期的限制，年初至今的增長意義不大，但符合我們的預期。對於第三季度，重要的是要記住，就 Alexion 而言，我們沒有完整的第三季度。所以我們沒有完整的銷售額，也沒有完整的研發支出和其他成本。

We're committed to following the science, and our news -- pipeline news flow in the quarter has been extraordinary, really, with 8 positive late-stage readouts across 7 medicines with the potential to challenge the standard of care in multiple diseases.

我們致力於追隨科學，我們的新聞——本季度的管道新聞流確實非同尋常，有 7 種藥物的 8 個積極的後期讀數，有可能挑戰多種疾病的護理標準。

So if you turn to Slide 7. The performance in the period were strong across our diversified business areas as well as across geographies. If you look specifically at the Emerging Markets region, growth was 10% year-to-date, excluding the contribution of the COVID-19 vaccine. China grew by 2% in the quarter due to price and volume pressures as well as stock compensations to distributors related to VBP and NRDL negotiations.

因此，如果您轉到幻燈片 7。在此期間，我們多元化的業務領域以及各個地區的表現都很強勁。如果您特別關注新興市場地區，今年迄今的增長率為 10%，不包括 COVID-19 疫苗的貢獻。由於價格和數量壓力以及與 VBP 和 NRDL 談判相關的經銷商的股票補償，中國在本季度增長了 2%。

The volume of key medicines is growing very strongly in China, but it's not fully compensating for price pressures. It is clear that China is slowing down but will remain a very important market for us. And over the next few years, we expect to continue growing with, of course, a variable growth rate depending on the year, but still a very important market that will contribute greatly to our company.

中國關鍵藥物的銷量增長非常強勁，但並不能完全彌補價格壓力。很明顯，中國正在放緩，但對我們來說仍將是一個非常重要的市場。在接下來的幾年裡，我們預計會繼續增長，當然，增長率會因年份而異，但仍然是一個非常重要的市場，將對我們公司做出巨大貢獻。

And the slower growth in China was compensated by the Emerging Markets that grew 30% in the quarter. So overall, the Emerging Markets, including China, grew by 12% in the quarter, again, excluding COVID-19 vaccine, which reflects the strength of our global footprint. We will provide additional commentary on China performance later in the presentation.

中國增長放緩被本季度增長 30% 的新興市場所彌補。因此，總體而言，包括中國在內的新興市場在本季度再次增長了 12%，不包括 COVID-19 疫苗，這反映了我們全球業務的實力。我們將在演示文稿的稍後部分提供有關中國表現的更多評論。

So please move to Slide 8. So if we look at the late-stage pipeline delivery, I would like to highlight a few regulatory approvals for 3 medicines: Farxiga for CKD in the EU and Japan, Saphnelo for SLE in the U.S. and Japan; and Ultomiris in the EU for children and adolescence with PNH. So we await regulatory decisions with great excitement for AZD7442, our long-acting antibody in COVID-19 prophylaxis and also in oncology for Enhertu in second-line HER2-positive breast cancer. And we are, of course, in the process of discussing potential orders for the -- for Evusheld, their lab, with countries around the world.

所以請轉到幻燈片 8。如果我們看一下後期管道交付，我想強調 3 種藥物的一些監管批准： Farxiga 在歐盟和日本用於 CKD， Saphnelo 在美國和日本用於 SLE；和 Ultomiris 在歐盟用於 PNH 的兒童和青少年。因此，我們對 AZD7442（我們在 COVID-19預防和 Enhertu 二線 HER2陽性乳腺癌的腫瘤學中的長效抗體）感到非常興奮地等待監管決定。當然，我們正在與世界各國討論他們的實驗室 Evusheld 的潛在訂單。

So if you move to Slide 9, I will now hand over to Aradhana Sarin, our new CFO, who joins us from Alexion, where she was the CFO. For those of you who have not met Aradhana, I know you'll be as impressed as I am with her knowledge of the industry, her sense of the business and her passion for our mission to help patients and follow the science.

因此，如果您轉到幻燈片 9，我現在將移交給我們的新首席財務官 Aradhana Sarin，她從擔任首席財務官的 Alexion 加入我們。對於那些沒有見過 Aradhana 的人，我知道你會和我一樣對她對行業的了解、她的商業意識以及她對我們幫助患者和遵循科學的使命的熱情印象深刻。

Again, a warm welcome to Aradhana and Alexion colleagues. Over to you, Aradhana.

再次熱烈歡迎 Aradhana 和 Alexion 的同事。交給你，阿拉達納。

Thank you, Pascal. I will be covering our financial performance for the third quarter and year-to-date 2021.

謝謝你，帕斯卡。我將介紹我們 2021 年第三季度和年初至今的財務業績。

Please turn to Slide 10. Total revenue grew by 28% year-to-date and by 48% in the third quarter. This includes our COVID-19 vaccine. Excluding the vaccine, total revenue grew by 17% year-to-date and by 32% in the third quarter with strong performance across our key disease areas.

請轉到幻燈片 10。總收入今年迄今增長了 28%，第三季度增長了 48%。這包括我們的 COVID-19 疫苗。不包括疫苗，總收入今年迄今增長 17%，第三季度增長 32%，在我們的關鍵疾病領域表現強勁。

Our reported EPS in the third quarter was negative at $1.10, impacted by an impairment charge of $1.2 billion following a strategic decision to discontinue the development of Verinurad from the acquisition of Ardea in 2012. Our reported numbers are also impacted by a number of adjustments following the consolidation of Alexion.

我們在第三季度報告的每股收益為負 1.10 美元，受到 2012 年收購 Ardea 後停止 Verinurad 開發的戰略決定後 12 億美元的減值費用的影響。我們報告的數字還受到以下一些調整的影響Alexion 的整合。

One of the main adjustments is in inventory where previously, Alexion held this at cost, whereas now it is recorded at fair value. As a result, cost of sales for the group was inflated by $1 billion charge related to the unwind of the inventory fair value uplift. On a reported basis, we expect the cost of sales to continue to be high for the next 18 months or so until this inventory is sold.

主要調整之一是庫存，以前，Alexion 按成本持有，而現在按公允價值記錄。結果，該集團的銷售成本被誇大了 10 億美元，這與庫存公允價值提升的解除有關。根據報告，我們預計未來 18 個月左右的銷售成本將繼續居高不下，直到該庫存售出。

We also incurred higher amortization charges this quarter as we start amortizing the Alexion medicines over their useful economic lives. These changes do not have an impact on our core results.

本季度我們還產生了更高的攤銷費用，因為我們開始對 Alexion 藥物的有用經濟壽命進行攤銷。這些變化不會影響我們的核心結果。

Please turn to the core P&L on Slide 11. The core gross margin was 74.1% year-to-date, driven by the vaccine. Excluding the vaccine, we saw a small decline in gross margin, in line with our previous comments on increased pricing pressure in China and profit-sharing arrangements on several successful medicines.

請轉到幻燈片 11 上的核心損益表。在疫苗的推動下，年初至今的核心毛利率為 74.1%。不包括疫苗，我們看到毛利率小幅下降，這與我們之前對中國定價壓力增加和幾種成功藥物的利潤分享安排的評論一致。

Core operating expenses increased 20% with year-on-year comparisons impacted by the addition of Alexion from 21st of July. Excluding the COVID-19 vaccine, core operating expenses increased by mid-teens percentage. Higher R&D costs are also reflected -- reflective of pipeline success in the last quarter with numerous successful late-stage readouts as well as our substantial investment in R&D for our long-acting COVID-19 antibody combination beyond the level of government funding.

從 7 月 21 日起，隨著 Alexion 的加入，核心運營費用同比增長 20%。不包括 COVID-19 疫苗，核心運營費用增加了十幾歲的百分比。更高的研發成本也反映出來——這反映了上一季度管道的成功，以及許多成功的後期讀數，以及我們對長效 COVID-19抗體組合的大量研發投資，超出了政府資助的水平。

The increase in SG&A costs reflect the addition of Alexion, increased investment in new launches, including Saphnelo in lupus and Farxiga on CKD as well as significant prelaunch investment following successful Phase III data for ENHERTU, LYNPARZA, tezepelumab and BD27. From a year-on-year comparison basis, you may recall that the SG&A costs in third quarter 2020 declined 1% compared to 2019 because of COVID-related lockdowns and cost reductions in areas such as T&E. This also skews the SG&A growth comparison. Core earnings per share of $3.59 a includes a negative impact of $0.03 from the vaccine with a $0.01 benefit in the third quarter.

SG&A 成本的增加反映了 Alexion 的加入、對新產品的投資增加，包括用於狼瘡的 Saphnelo 和用於 CKD 的 Farxiga 以及在 ENHERTU 、 LYNPARZA 、 tezepelumab 和 BD27成功獲得 III 期數據後的重大上市前投資。從同比比較來看，您可能還記得，由於與 COVID 相關的封鎖和 T&E 等領域的成本降低，2020 年第三季度的 SG&A 成本與 2019 年相比下降了 1%。這也扭曲了 SG&A 增長比較。每股 3.59 美元的核心收益包括疫苗帶來的 0.03 美元的負面影響以及第三季度 0.01 美元的收益。

Now turning to Slide 12. In the quarter, we saw further improvement in our core operating profit mix and core operating profit increased quarter-on-quarter, benefiting from the inclusion of Alexion despite lower other operating income. We're updating our 2021 guidance to provide further details around the contribution of our COVID-19 medicines.

現在轉到幻燈片 12。在本季度，我們看到我們的核心運營利潤組合進一步改善，核心運營利潤環比增長，這得益於 Alexion 的加入，儘管其他運營收入有所下降。我們正在更新我們的 2021 年指南，以提供有關我們 COVID-19 藥物貢獻的更多詳細信息。

While we continue to expect the percentage increase in total revenue, excluding the contribution from the COVID-19 vaccine in line with our prior guidance, we now expect total revenues to increase by mid- to high 20s percentage inclusive of fourth quarter vaccine sales. We anticipate fourth quarter of our original agreement and new commercial Vaxzevria contract, but with the vast majority coming from pandemic agreements.

雖然我們繼續預計總收入的百分比增長，不包括符合我們先前指導的 COVID-19 疫苗的貢獻，但我們現在預計總收入將增加 20% 的中高百分比，包括第四季度的疫苗銷售。我們預計第四季度的原始協議和新的商業 Vaxzevria 合同，但絕大多數來自大流行協議。

In line with prior years, we expect a step-up in total revenue in the fourth quarter. Any net profit from commercial vaccine contracts in the fourth quarter is expected to be modest and to offset continued investment in R&D and supporting activities such as pharmacovigilance for COVID-19 medicines, including the long-acting antibody resulting in no material EPS contribution from these medicines in 2021. We still expect core earnings per share to be between $5.05 and $5.40 at constant exchange rate for 2021, in line with our prior guidance.

與往年一樣，我們預計第四季度總收入將有所增長。預計第四季度商業疫苗合同的任何淨利潤都將是適度的，並將抵消對研發和支持活動的持續投資，例如 COVID-19藥物的藥物警戒，包括導致這些藥物沒有實質性每股收益貢獻的長效抗體到 2021 年。我們仍預計 2021 年按固定匯率計算的每股核心收益將在 5.05 美元至 5.40 美元之間，這與我們之前的指導一致。

Please turn to Slide 13. Net debt increased to $24.7 billion following the completion of the Alexion transaction. That leaves our current net debt-to-EBITDA ratio at around 3.1x. Our EBITDA is, however, reduced by the $1 billion unwind of the Alexion inventory fair value adjustment discussed previously.

請轉到幻燈片 13。Alexion 交易完成後，淨債務增加到 247 億美元。這使得我們目前的淨債務與 EBITDA 的比率約為 3.1 倍。然而，我們的 EBITDA 因之前討論的 Alexion 庫存公允價值調整的 10 億美元而減少。

Excluding this noncash impact, our net debt-to-EBITDA ratio would reduce about 2.7x. As previously communicated, we're committed to rapidly reducing our debt. Our capital allocation priorities remain unchanged. In no specific order, we aim to maintain a strong investment-grade rating while continuing to reinvest in the business. We will also continue to explore strategic, value-enhancing business development opportunities and remain committed to our progressive dividend policy, defined as stable or increasing dividend.

排除這種非現金影響，我們的淨債務與 EBITDA 比率將降低約 2.7 倍。如前所述，我們致力於迅速減少債務。我們的資本配置重點保持不變。沒有特定的順序，我們的目標是保持強大的投資級評級，同時繼續對業務進行再投資。我們還將繼續探索戰略性、增值業務發展機會，並繼續致力於我們的累進股息政策，即穩定或增加的股息。

I will now hand over to Dave Fredrickson.

我現在將交給戴夫弗雷德里克森。

Thank you, and welcome, Aradhana. Slide 14, please. So we're pleased to report that our oncology total revenue grew 16%, a good performance, showing the momentum of new launches and the diversity of our portfolio in the face of continued headwinds from COVID-19. With that said, diagnosis rates continue to improve and are now around 5% to 10% below pre-COVID levels. The quarter included strong performances from Calquence and Enhertu, solid delivery from Lynparza and Imfinzi. And on Tagrisso, the year-to-date showed growth. However, sequential sales for the quarter were slightly down due to China dynamics, which I'll explain shortly.

謝謝你，歡迎你，阿拉達納。請幻燈片 14。因此，我們很高興地報告，面對 COVID-19 的持續逆風，我們的腫瘤學總收入增長了 16%，表現良好，顯示了新產品發布的勢頭和我們產品組合的多樣性。話雖如此，診斷率繼續提高，現在比 COVID 之前的水平低 5% 到 10% 左右。本季度包括 Calquence 和 Enhertu 的強勁表現，Lynparza 和 Imfinzi 的穩健交付。在 Tagrisso 上，年初至今顯示出增長。然而，由於中國的動態，本季度的環比銷售額略有下降，我稍後將對此進行解釋。

So let's turn to Slide 15 and go through some of the specifics. In the U.S., underlying volume demand for Tagrisso continues to grow at low single-digit rates, with rising first-line duration of treatment and increasing adjuvant use driving sales, partially offset by lower second-line use and the pandemic impact on diagnosis and testing. More specifically, in adjuvant use, we're pleased with the good progress we've been making in moving physician practice. However, it takes time for the relatively small number of new starts in a setting that is 20% to 25% of the size of the first-line metastatic market to move the dial on overall prescriptions.

因此，讓我們轉到幻燈片 15 並了解一些細節。在美國，對 Tagrisso 的潛在需求量繼續以低個位數的速度增長，一線治療持續時間增加和輔助使用增加推動銷售，部分被二線使用減少和大流行對診斷和測試的影響所抵消.更具體地說，在輔助使用方面，我們對我們在推動醫師實踐方面取得的良好進展感到高興。然而，在一個佔一線轉移性市場規模 20% 至 25% 的環境中，相對較少的新開始治療需要時間來推動整體處方的變化。

In emerging markets, growth in the year-to-date was 1%. Within that, we've seen strong growth in EM outside China as Tagrisso gained reimbursement in more markets. In China, the strong volume growth we are seeing in the first line and second line is still catching up with the price discount for NRDL inclusion in March.

在新興市場，今年迄今的增長率為 1%。其中，隨著泰瑞沙在更多市場獲得報銷，我們看到中國以外新興市場的強勁增長。在中國，我們在一線和二線看到的強勁銷量增長仍在趕上 3 月份納入 NRDL 的價格折扣。

Following the NRDL change, in the second quarter, we saw inventory build and a bolus due to first-generation TKI switches in the front line. In the third quarter, we are down sequentially as those factors were not at play. We're confident we're moving the needle in China in frontline and maintaining robust share in second line. We expect continued volume growth to offset the cut in price that we took in the coming months and for Tagrisso to resume top line growth in China at that point.

隨著國家醫保目錄的變化，在第二季度，由於第一代 TKI 交換機在一線，我們看到庫存增加和推注。在第三季度，我們連續下降，因為這些因素沒有發揮作用。我們有信心在一線推動中國市場的發展，並在二線保持強勁的份額。我們預計持續的銷量增長將抵消我們在未來幾個月內採取的降價措施，並且屆時泰瑞沙將恢復在中國的收入增長。

Turning to our immuno-oncology franchise. Imfinzi grew by 17% in the year-to-date. We're very pleased that we continue to grow Imfinzi over the last several quarters despite the pandemic solidifying and growing Pacific and driving successful launches of CASPIAN in the face of competition. All of that sets a great foundation for launches in some of the potential new indications that Susan will speak about in a few moments.

轉向我們的免疫腫瘤專營權。今年迄今，Imfinzi 增長了 17%。我們很高興我們在過去幾個季度繼續發展 Imfinzi，儘管大流行正在鞏固和發展太平洋，並在競爭中推動 CASPIAN 的成功推出。所有這些都為 Susan 稍後將談到的一些潛在新跡象的發布奠定了良好的基礎。

Please turn to Slide 16. Lynparza continued to deliver strong growth across tumor types and territories, increasing product sales by 31% to $1.7 billion in the first 9 months of the year. Lynparza remains the class-leading PARP inhibitor across 4 tumor types. U.S. sales were up 26%, driven by greater use in ovarian, prostate and adjuvant breast cancer. And we are pleased to see the NCCN guidelines updated to include OlympiA during Q3.

請轉到幻燈片 16。 Lynparza 繼續在腫瘤類型和地區實現強勁增長，今年前 9 個月的產品銷售額增加了 31% 至 17 億美元。 Lynparza 仍然是 4 種腫瘤類型的領先 PARP 抑製劑。受卵巢癌、前列腺癌和輔助性乳腺癌的更多使用推動，美國的銷售額增長了 26%。我們很高興看到 NCCN 指南在第三季度更新為包括 OlympiA。

Europe and established Rest of World showed good growth in ovarian and prostate cancer, supported by continued growth in HRD testing. China benefited from strong volume growth due to the expanded ovarian cancer indication in the NRDL for March offset by the associated price cut as well as similar, albeit smaller, inventory phasing headwinds in Q3 as seen with Tagrisso.

歐洲和世界其他地區的卵巢癌和前列腺癌顯示出良好的增長，這得益於 HRD 檢測的持續增長。中國受益於強勁的銷量增長，原因是 3 月份 NRDL 中擴大的卵巢癌適應症被相關的降價以及與 Tagrisso 所見的第三季度類似但較小的庫存階段性逆風所抵消。

Please turn to Slide 17. Calquence continues to make strong progress towards blockbuster status, driven by a robust share performance in the U.S. in chronic lymphocytic leukemia where it has reached 52% new patient share. Calquence has continued to show good momentum in Europe as well with several launches, including France, Germany and the U.K. off to good success.

請轉至幻燈片 17。 Calquence 繼續在重磅炸彈狀態方面取得強勁進展，這得益於美國慢性淋巴細胞白血病的強勁份額表現，其新患者份額已達到 52%。 Calquence 在歐洲也繼續表現出良好的勢頭，包括法國、德國和英國在內的幾次發布都取得了良好的成功。

Moving on to Enhertu, the year-to-date saw good momentum in third-line breast and second-line gastric cancer. That success came against a backdrop of new clinical data that establishes tremendous opportunities for Enhertu in the years to come. Susan will talk to the data from DESTINY-Breast03 in a moment. And I won't steal her thunder, but with Enhertu, now the established leader in third-line HER2-positive breast cancer, we have the critical platform to really drive changes in the standards of care in second line once these data get approved.

繼續前進到 Enhertu，年初至今，三線乳腺癌和二線胃癌的發展勢頭良好。這一成功是在新的臨床數據的背景下取得的，這些數據為 Enhertu 在未來幾年創造了巨大的機會。蘇珊一會兒會談到來自 DESTINY-Breast03 的數據。而且我不會搶走她的風頭，但有了 Enhertu，現在是三線 HER2 陽性乳腺癌的公認領導者，一旦這些數據獲得批准，我們就有了真正推動二線護理標準變化的關鍵平台。

I'll now hand over to Susan to discuss our R&D progress.

我現在請蘇珊討論我們的研發進展。

Thank you, Dave. Please turn to Slide 18. I want to take a minute to account the outstanding results from DESTINY-Breast03 trial that were presented at ESMO. We saw a highly clinically meaningful and statistically significant improvement in progression-free survival compared to trastuzumab-DM1 and as well as a trend in overall survival at this very immature analysis. Enhertu truly has the capacity to change the standard of care by demonstrating superior benefit over trastuzumab-DM1 in patients with HER2-positive metastatic breast cancer in the second line.

謝謝你，戴夫。請轉到幻燈片 18。我想花一點時間來介紹一下在 ESMO 上展示的 DESTINY-Breast03 試驗的出色結果。與曲妥珠單抗-DM1相比，我們看到了無進展生存期的高度臨床意義和統計學上顯著的改善，以及在這項非常不成熟的分析中的總生存期趨勢。 Enhertu 確實有能力通過在二線治療 HER2 陽性轉移性乳腺癌患者中證明優於曲妥珠單抗-DM1 的優勢來改變護理標準。

As a result, we were pleased to see the recent ESMO guideline update adding Enhertu as the new standard of care in this setting. No new safety concerns were identified, and importantly, no Grade 4 or 5 treatment-related interstitial lung disease events were observed. This is very encouraging for the potential use of Enhertu in earlier lines of therapy. We also saw in Enhertu granted Breakthrough Therapy designation status by the FDA on the back of the DESTINY-Breast03 studies, a real testament to the importance and impact these data will have on patient outcomes.

因此，我們很高興看到最近的 ESMO 指南更新將 Enhertu 添加為該環境中的新護理標準。沒有發現新的安全問題，重要的是，沒有觀察到 4 級或 5 級治療相關的間質性肺病事件。這對於 Enhertu 在早期治療中的潛在應用是非常令人鼓舞的。我們還在 Enhertu 中看到 FDA 在 DESTINY-Breast03 研究的背景下授予了突破性治療指定地位，這真實地證明了這些數據將對患者結果產生的重要性和影響。

During the period, Lynparza became the first PARP inhibitor to generate positive data in first-line metastatic castration-resistant prostate cancer in combination with abiraterone in an all-comers population. Prostate cancer is the second most common and the fifth leading cause of cancer death in men globally, and new chemotherapy-free options are desperately needed.

在此期間，Lynparza 成為第一個 PARP 抑製劑在一線轉移性去勢抵抗性前列腺癌中與阿比特龍聯合在所有人群中產生陽性數據。前列腺癌是全球男性癌症死亡的第二大常見原因和第五大癌症死亡原因，迫切需要新的無化療方案。

Please turn to Slide 19. Gastrointestinal cancers such as liver cancer are common and have seen limited innovation when it comes to improving clinical outcomes for patients. Recently, we reported back-to-back positive readouts for our immuno-oncology franchise, with HIMALAYA in hepatocellular carcinoma and TOPAZ-1 in advanced biliary tract cancer. Both indications have a large unmet need as recognized by their U.S. orphan drug designations. These data open up the potential for Imfinzi and tremelimumab in a broader array of settings and brings us closer to our goal to improve long-term survival for patients with different gastrointestinal cancers.

請轉到幻燈片 19。肝癌等胃腸道癌症很常見，在改善患者臨床結果方面的創新有限。最近，我們報告了我們的免疫腫瘤專營權的背靠背陽性讀數，其中 HIMALAYA 用於肝細胞癌，而 TOPAZ-1 用於晚期膽道癌。這兩種適應症都有很大的未滿足需求，正如它們的美國孤兒藥指定所承認的那樣。這些數據為 Imfinzi 和 tremelimumab 在更廣泛的環境中開闢了潛力，並使我們更接近我們的目標，即提高不同胃腸道癌症患者的長期生存率。

In HIMALAYA, a single high priming dose of tremelimumab added to Imfinzi, known as the STRIDE regimen, resulted in a clinically meaningful improvement in overall survival when compared to the current standard of care. This regimen was selected after careful analysis of clinical and biomarker data from various trials with different tremelimumab dosing schedules.

在 HIMALAYA，與目前的護理標準相比，在 Imfinzi 中添加單次高啟動劑量的曲美木單抗（稱為 STRIDE 方案）導致總體生存率有臨床意義的改善。該方案是在仔細分析來自不同tremelimumab給藥方案的各種試驗的臨床和生物標誌物數據後選擇的。

In the TOPAZ-1 trial at a planned interim analysis, Imfinzi, when used in combination with standard of care chemotherapy of gemcitabine plus cisplatin, demonstrated an improvement in overall survival in patients versus chemotherapy alone. This is the first major global treatment breakthrough in first-line advanced biliary tract cancer in over a decade.

在計劃進行的中期分析的 TOPAZ-1 試驗中，Imfinzi 與吉西他濱加順鉑的標準護理化療聯合使用時，與單獨化療相比，患者的總生存期有所改善。這是十多年來一線晚期膽道癌的第一個重大全球治療突破。

Our development plan for Imfinzi in liver cancer does not stop here as we eagerly await results from the EMERALD-1 trial, which will evaluate the use of Imfinzi in patients with local regional hepatocellular cancer who are not amenable to curative therapy. This is in line with our strategy to move into treating earlier stages of disease. EMERALD-1 will read out in the second half of next year.

我們在肝癌中的 Imfinzi 開發計劃並沒有止步於此，因為我們急切地等待 EMERALD-1 試驗的結果，該試驗將評估 Imfinzi 在不適合治愈性治療的局部區域肝細胞癌患者中的使用。這符合我們進入治療早期疾病階段的策略。 EMERALD-1 將於明年下半年宣讀。

Please turn to Slide 20. And now what's next? We have multiple Phase III trials starting across our pipeline. MONO-OLA1 is a trial in first-line ovarian cancer for Lynparza and also have the VOLGA trial in muscle-invasive bladder cancer for Imfinzi. We'll also start a new trial for Enhertu called DESTINY-Lung04, along with [TROPION-Breast01] for datopotamab deruxtecan with our collaborators, Daiichi Sankyo.

請轉到幻燈片 20。現在下一步是什麼？我們的管道開始進行多項 III 期試驗。 MONO-OLA1是 Lynparza 的一線卵巢癌試驗，還有 Imfinzi 的肌肉浸潤性膀胱癌的 VOLGA 試驗。我們還將與合作者 Daiichi Sankyo 一起開始一項名為 DESTINY-Lung04 的 Enhertu 新試驗，以及 datopotamab deruxtecan 的 [TROPION-Breast01]。

We also have 2 new bispecifics that have entered Phase I trials in solid tumors. AZD2936, which is a PD-1 TIGIT bispecific, as well as AZD7789, a PD-1 TIM3 bispecific. Both of these have the potential to become next-generation immuno-oncology therapies. I look forward to updating you on the progress of these and other programs soon.

我們還有 2 個新的雙特異性藥物已進入實體瘤的 I 期試驗。 AZD2936 是一種 PD-1 TIGIT 雙特異性藥物，AZD7789 是一種 PD-1 TIM3 雙特異性藥物。這兩者都有可能成為下一代免疫腫瘤療法。我期待著盡快向您通報這些計劃和其他計劃的進展情況。

I'm now going to hand over to Ruud to take you through the BioPharmaceuticals and Emerging Markets performance in the period. Please turn to Slide 21.

我現在將交給 Ruud 帶您了解該期間的生物製藥和新興市場表現。請轉到幻燈片 21。

Thank you, Susan. Please turn to Slide 22. In CVRM, total revenue was up 10% to $6 billion, with the vast majority of growth coming from Farxiga's continued strong performance. Farxiga grew 51% and remains the largest single contributor to AstraZeneca's growth. Farxiga also continued its remarkable progress as the fastest-growing SGLT2 inhibitor globally, making gains in volume market share boosted by successful launches in heart failure and chronic kidney disease.

謝謝你，蘇珊。請轉到幻燈片 22。在 CVRM 中，總收入增長了 10%，達到 60 億美元，其中絕大部分增長來自 Farxiga 的持續強勁表現。 Farxiga 增長了 51%，並且仍然是阿斯利康增長的最大單一貢獻者。 Farxiga 還繼續其作為全球增長最快的 SGLT2抑製劑的顯著進展，在心力衰竭和慢性腎病領域的成功推出推動了銷量市場份額的增長。

Following the results of the DAPA-HF trial, we were pleased to see the European Society of Cardiology guidelines updated to include Farxiga as first-line treatment for heart failure patients with reduced ejection fraction. Additionally, ESC guidelines now also recommend novel potassium binders, such as Lokelma to treat hyperkalemia, which is great news for patients. Lokelma revenues more than doubled to $122 million. In the United States, Lokelma reinforced its leadership in the branded potassium binder market, reaching 58% share of prescriptions. And in Japan, its market share increased to 41%.

根據 DAPA-HF 試驗的結果，我們很高興看到歐洲心髒病學會指南更新，將 Farxiga 作為射血分數降低的心力衰竭患者的一線治療。此外，ESC 指南現在還推薦新型鉀結合劑，例如 Lokelma 來治療高鉀血症，這對患者來說是個好消息。 Lokelma 的收入增長了一倍多，達到 1.22 億美元。在美國，Lokelma 鞏固了其在品牌鉀粘合劑市場的領導地位，達到了 58% 的處方份額。而在日本，其市場份額增至41%。

Please move to Slide 23. Turning to Respiratory & Immunology. Total revenue was $4.5 billion, with a growth rate of 12%. The year-on-year growth benefited from the effects of COVID-19 on last year's Pulmicort sales. Fasenra delivered product sales of $901 million, up 32% and is the leading respiratory biologic prescribed for eosinophilic asthma globally. Fasenra's performance has been driven by sustained growth in new-to-brand patient starts in both the U.S. and the EU. Recently, Fasenra as granted orphan drug designations in eosinophilic gastroenteritis and eosinophilic gastritis and a Fast-Track designation for the treatment of EG with or without EGE by the U.S. FDA.

請移至幻燈片 23。轉向呼吸與免疫學。總收入為 45 億美元，增長率為 12%。同比增長得益於 COVID-19 對去年 Pulmicort 銷售的影響。 Fasenra 的產品銷售額為 9.01 億美元，增長 32%，是全球用於治療嗜酸性哮喘的領先呼吸生物製劑。 Fasenra 的業績受到美國和歐盟新品牌患者開始的持續增長的推動。最近，Fasenra 被美國 FDA 授予嗜酸性胃腸炎和嗜酸性胃炎的孤兒藥稱號，以及治療伴或不伴 EGE 的快速通道指定。

Breztri with product sales of $130 million continued its global launch trajectory, rapidly gaining market share in the fast-growing triple fixed-dose combination class. Breztri is now approved in 36 countries, including China, where we are seeing patient volume increase following NRDL inclusion earlier this year.

產品銷售額為 1.3 億美元的 Breztri 繼續其全球上市軌跡，在快速增長的三聯固定劑量組合類別中迅速獲得市場份額。 Breztri 現在已在包括中國在內的 36 個國家獲得批准，我們看到在今年早些時候納入 NRDL 後患者數量有所增加。

Symbicort sales were $2 billion, a slight decrease of 3% against a tough comparison from COVID-19-related stock last year. Symbicort remains the #1 ICS/LABA globally and has to date received 42 approvals worldwide towards use as a rescue therapy for asthma.

Symbicort 的銷售額為 20 億美元，與去年與 COVID-19 相關的股票相比略有下降 3%。 Symbicort 仍然是全球排名第一的 ICS/LABA，迄今為止已在全球範圍內獲得 42 項批准，用於作為哮喘的搶救療法。

Please turn to Slide 24. Now on to the emerging markets. Excluding revenue from the COVID-19 vaccine, total revenue grew 10% to $7.5 billion. Growth in China for the period was 8% and growth of emerging markets ex China was 14%. Tagrisso grew 1% in the emerging markets, reflecting the impact of the inventory phasing in China, which Dave described earlier.

請轉到幻燈片 24。現在轉到新興市場。不包括 COVID-19 疫苗的收入，總收入增長 10% 至 75 億美元。同期中國的增長率為 8%，中國以外的新興市場增長率為 14%。 Tagrisso 在新興市場增長了 1%，反映了 Dave 之前描述的中國庫存分階段的影響。

Farxiga has had remarkable growth of 74% in the period as it continues to benefit from increased patient access in China following NRDL inclusion last year as well as broader access across other markets in the region. Pulmicort in China experienced some recovery from the impact of COVID-19. This comes ahead of the anticipated impact of its inclusion into the VBP program in October. Outside of China, we saw broad-based growth across all regions. Excluding the impact of the COVID-19 vaccine, total revenue growth increased by 9% in Asia Pacific, 12% in the Middle East and Africa, 28% in Latin America and 15% in Russia.

Farxiga 在此期間實現了 74% 的顯著增長，因為它繼續受益於去年納入 NRDL 後中國患者准入的增加以及該地區其他市場的更廣泛准入。中國的普米克從 COVID-19 的影響中經歷了一些恢復。這是在 10 月份將其納入 VBP 計劃的預期影響之前發生的。在中國以外，我們看到所有地區的廣泛增長。排除 COVID-19 疫苗的影響，亞太地區總收入增長 9%，中東和非洲增長 12%，拉丁美洲增長 28%，俄羅斯增長 15%。

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。

Thank you, Ruud. Please turn to Slide 25. Our respiratory and immunology portfolio continues to deliver. And in August, Saphnelo anifrolumab was approved to treat moderate to severe systemic lupus erythematosus in the U.S. and in Japan. In Europe, an ad hoc expert group meeting has been scheduled where we look forward to discussing the clinical data.

謝謝你，路德。請轉到幻燈片 25。我們的呼吸和免疫學產品組合繼續提供。 8 月，Saphnelo anifrolumab 在美國和日本被批准用於治療中度至重度系統性紅斑狼瘡。在歐洲，已經安排了一次特設專家組會議，我們期待著討論臨床數據。

This quarter, we also announced positive high-level results for the MANDALA and DENALI trials for PT027, our fixed-dose combination of albuterol and budesonide, and we anticipate regulatory submissions to be completed in the first half of next year.

本季度，我們還宣布了 PT027（我們的沙丁胺醇和布地奈德的固定劑量組合）的 MANDALA 和 DENALI 試驗的積極高水平結果，我們預計將在明年上半年完成監管提交。

Also in the quarter, Tezepelumab was granted Priority Review for the treatment of asthma, accelerating the review time lines of this much needed treatment option. Tezepelumab also received orphan drug designation for the treatment of eosinophilic esophagitis.

同樣在本季度，Tezepelumab 獲得了治療哮喘的優先審查，加快了這一急需治療方案的審查時間。 Tezepelumab 還獲得了治療嗜酸性食管炎的孤兒藥資格。

Please turn to Slide 26. We continue to see accumulating real-world evidence that shows the enormous contribution our COVID-19 vaccine, Vaxzevria, has made in preventing hundreds of thousands of hospital admissions and deaths. And we were really proud to be one of the recipients of the Prix Galien, Roy Vagelos, Pro Bono Humanum Award for the development of our COVID-19 vaccine.

請轉到幻燈片 26。我們繼續看到越來越多的真實證據表明我們的 COVID-19 疫苗 Vaxzevria 在防止數十萬人住院和死亡方面做出了巨大貢獻。我們真的很自豪能夠成為 Prix Galien、Roy Vagelos、Pro Bono Humanum 獎的獲得者之一，因為我們開發了我們的 COVID-19 疫苗。

Turning to AZD7442, which will be known as Evusheld, we announced positive results from both the PROVENT prophylaxis study in the TACKLE Phase III trials, which is a treatment study. And AZD7442 is the only long-acting antibody combination that has demonstrated the ability to both prevent and treat COVID-19 disease.

談到將被稱為 Evusheld 的 AZD7442，我們宣布了 TACKLE III 期試驗中 PROVENT 預防研究的積極結果，這是一項治療研究。 AZD7442 是唯一一種已證明能夠預防和治療 COVID-19 疾病的長效抗體組合。

In prophylaxis, there's a significant unmet medical need to protect vulnerable populations who've an inadequate response to vaccines such as those who are immunocompromised by disease or their therapy. And AZD7442 is a convenient intramuscular injection and has the potential to protect these individuals for up to 12 months. We anticipate emergency use authorization in the U.S. towards the end of the year and have active review processes across Europe and the U.K.

在預防方面，保護對疫苗反應不足的弱勢群體（例如因疾病或其治療而免疫功能低下的人群）存在重大未滿足的醫療需求。 AZD7442 是一種方便的肌肉注射劑，有可能保護這些人長達 12 個月。我們預計美國將在年底前獲得緊急使用授權，並在歐洲和英國開展積極的審查流程。

We recently presented data from the MELODY and MEDLEY trials for nirsevimab, which showed it is a highly effective at reducing medically-attended lower respiratory tract infections and has a similar safety profile to Synagis. Regulatory submissions for nirsevimab are expected to complete in the first half of next year.

我們最近展示了 nirsevimab 的 MELODY 和 MEDLEY 試驗數據，這表明它在減少就診下呼吸道感染方面非常有效，並且與 Synagis 具有相似的安全性。 nirsevimab 的監管提交預計將在明年上半年完成。

And finally, taking a look at what's next. If we turn to Slide 27, please. This quarter, we saw results for cotadutide, our GLP/glucagon co-agonist for the treatment of NASH and diabetic kidney disease, which we presented in due course, as well as Phase II data for AZD8233, our PCSK9 inhibitor for dyslipidemia. We also initiated Phase II trials forAZD4604, our inhaled JAK inhibitor for the treatment of asthma.

最後，看看接下來會發生什麼。請轉到幻燈片 27。本季度，我們看到了用於治療 NASH 和糖尿病腎病的 GLP/胰高血糖素聯合激動劑 cotadutide 的結果，我們適時公佈了這些結果，以及我們用於血脂異常的 PCSK9 抑製劑 AZD8233 的 II 期數據。我們還啟動了 AZD4604 的 II 期試驗，這是我們用於治療哮喘的吸入 JAK 抑製劑。

Please go to Slide 28, as I now hand over to Marc to cover rare diseases.

請轉到第 28 張幻燈片，因為我現在交給 Marc 來報導罕見疾病。

Thank you, Mene. I'm happy to join you today in my new role as Chief Executive Officer of Alexion and excited to be part of Alexion's next chapter with AstraZeneca. To recall Pascal's earlier comments, I want to thank all of the Alexion employees across the globe for their continued dedication to the patients we serve.

謝謝你，梅內。我很高興今天加入您擔任 Alexion 首席執行官的新職務，並很高興能成為 Alexion 與阿斯利康的新篇章的一部分。回顧 Pascal 之前的評論，我要感謝全球所有 Alexion 員工對我們服務的患者的持續奉獻。

Since it is AstraZeneca's first quarter with Alexion, I wanted to briefly provide an overview of the business to help more of you become acquainted with rare disease. Please turn to Slide 29. The combination of AstraZeneca and Alexion presents a unique opportunity to accelerate AstraZeneca's strategic and financial development. Alexion's [fibrate] for medicine for the treatment of over 7 rare and devastating diseases, including the leading C5 franchise comprised of Soliris and Ultomiris.

由於這是阿斯利康與 Alexion 合作的第一季度，我想簡要介紹一下該業務，以幫助更多人熟悉罕見病。請轉到幻燈片 29。阿斯利康和 Alexion 的合併為加速阿斯利康的戰略和財務發展提供了獨特的機會。 Alexion 的 [fibrate] 用於治療超過 7 種罕見和破壞性疾病的藥物，包括由 Soliris 和 Ultomiris 組成的領先 C5 特許經營權。

Alexion has a strong commercial and financial track record, achieving best-in-class conversion to Ultomiris in less than 18 months from launch and delivering over $6 billion in total revenue in 2020, representing 21% growth from prior year. This performance relates to the period before the merger with AstraZeneca.

Alexion 擁有強大的商業和財務記錄，在推出後不到 18 個月的時間內實現了向 Ultomiris 的一流轉換，並在 2020 年實現了超過 60 億美元的總收入，比上年增長 21%。這一表現與與阿斯利康合併之前的時期有關。

On the R&D side, we continue to innovate in complement with novel C5 inhibitors, including a subcutaneous formulation of Ultomiris and ALXN1720, the subcutaneous minibody. Outside of terminal complement, we have 2 oral Factor D medicine. We also have ALXN1820, a subcutaneous anti-properdin with potential application in multiple disease areas. Overall, we have a diversified development portfolio of novel technology platforms and medicines that has the potential to deliver attractive growth opportunities.

在研發方面，我們繼續創新補充新的 C5 抑製劑，包括 Ultomiris 和 ALXN1720（皮下微型抗體）的皮下製劑。在終末補體之外，我們有 2 種口服因子 D 藥物。我們還有 ALXN1820，一種皮下抗備解素，在多種疾病領域具有潛在應用。總體而言，我們擁有多元化的新技術平台和藥物開發組合，有可能帶來有吸引力的增長機會。

Turning now to Slide 30. This is an early look at how we plan to establish scientific bridges between Alexion and AstraZeneca to build a stronger combined organization. On the development side, we continue to see potential to apply Alexion's leadership in complement science to AstraZeneca's broader immunology efforts as well as bringing AstraZeneca with precision medicine expertise to rare disease.

現在轉到幻燈片 30。這是我們計劃如何在 Alexion 和 AstraZeneca 之間建立科學橋樑以建立一個更強大的聯合組織的早期研究。在開發方面，我們繼續看到將 Alexion 在補充科學領域的領導地位應用於阿斯利康更廣泛的免疫學工作以及將阿斯利康的精準醫學專業知識應用於罕見病的潛力。

In early research, collaboration with AstraZeneca gene editing, the gene therapy and oligonucleotide capabilities has potential to lead to the development of novel rare disease medicine. I look forward to seeing this initial effort progress towards new opportunities to deliver transformative medicine to patients.

在早期研究中，與阿斯利康基因編輯、基因治療和寡核苷酸能力的合作有可能導致新型罕見病藥物的發展。我期待看到這一初步努力朝著為患者提供變革性醫學的新機會而取得進展。

Please turn to Slide 31. Rare disease year-to-date total revenue was $1.3 billion, representing 6% quarter-on-quarter pro forma growth. Total revenue in the period were driven by strong Soliris volume growth in neurology indications and successful conversion to Ultomiris. Looking ahead, we expect growth to be broadly in line with that of the new and larger AstraZeneca on a compounded growth rate basis.

請轉到幻燈片 31。罕見病年初至今的總收入為 13 億美元，環比增長 6%。該期間的總收入受到神經病學適應症的 Soliris 銷量強勁增長和成功轉換為 Ultomiris 的推動。展望未來，我們預計在復合增長率的基礎上，增長將與新的和更大的阿斯利康大體保持一致。

We reported positive Phase III for Ultomiris in generalized myasthenia gravis with compelling efficacy observed as early as 1 week and sustain out to 52 weeks. Unfortunately, we announced discontinuation of the Phase III for Ultomiris in ALS on the recommendation of the Independent Data Monitoring Committee. While this was a high-risk program, we are nonetheless disappointed in this outcome.

我們報告了 Ultomiris 在全身性重症肌無力中的陽性 III 期，早在 1 週就觀察到令人信服的療效，並持續至 52 週。不幸的是，根據獨立數據監測委員會的建議，我們宣布終止 ALS 中 Ultomiris 的 III 期臨床試驗。雖然這是一項高風險計劃，但我們仍然對這一結果感到失望。

We reported positive Phase III results for ALXN1840 in Wilson disease, demonstrating superiority versus standard of care on the primary endpoint of copper mobilization. Finally, Alexion exercised the option to fully acquire Caelum Biosciences and accelerate the Phase III development of CAEL-101 in amyloidosis, the rare plasma cell dysplasia characterized by autonomous proliferation of plasma cell with overproduction of monoclonal immunoglobulin G.

我們報告了 ALXN1840 在威爾遜病中的積極 III 期結果，證明了在銅動員的主要終點上優於標準護理。最後，Alexion 行使了完全收購 Caelum Biosciences 的選擇權，並加速 CAEL-101在澱粉樣變性中的 III 期開發，澱粉樣變性是一種罕見的漿細胞發育異常，其特徵是漿細胞自主增殖和單克隆免疫球蛋白 G 的過量產生。

Please turn to Slide 32. Total revenue for Soliris declined by 2%, impacted by prior year order timing in emerging markets. Ultomiris grew by 31% in the period, driven by strong conversion from Soliris and 14 new country launches year-to-date. Strensiq grew by 8% in the period due to underlying growth in the United States.

請轉至幻燈片 32。 Soliris 的總收入下降了 2%，受上年新興市場訂單時間的影響。在此期間，Ultomiris 增長了 31%，這得益於 Soliris 的強勁轉換以及年初至今的 14 個新國家/地區的推出。由於美國的潛在增長，Strensiq 在此期間增長了 8%。

Finally, what's next on Slide 33. In July, we do the first patient in our Phase III Ultomiris trial in complement-mediated thrombotic microangiopathy, one of the multiple label expansion opportunities. We also made progress with ALXN1850, our next-generation asfotase alfa now in Phase I for the treatment of hypophosphatasia, a rare genetic bone disorder, often diagnosed in infancy or early childhood.

最後，幻燈片 33 上的下一步是什麼。7 月，我們在補體介導的血栓性微血管病的 III 期 Ultomiris 試驗中進行了第一位患者，這是多標籤擴展機會之一。我們還在 ALXN1850 方面取得了進展，我們的下一代 asfotase alfa 目前處於 I 期，用於治療低磷酸酯酶症，這是一種罕見的遺傳性骨骼疾病，通常在嬰儿期或兒童早期被診斷出來。

8As we move to Slide 34, we now turn back to Pascal for closing remarks.

8 當我們轉到幻燈片 34 時，我們現在回到帕斯卡的結束語。

Thank you, Marc. I will end on this Slide #35, please, that illustrates our news flow. Can I get Slide 35? It illustrates the news flow across the company in the coming months. In oncology, we anticipate data from Enhertu DESTINY-Breast04 trial in HER2 low breast cancer in the first half of next year as well as multiple Imfinzi readouts across lung and cervical cancers. In CVRM, we will have data from the DELIVER trial for Farxiga and HFpEF and in rare disease, data from in Ultomiris and NMOSD. We remain on track to deliver our full year guidance. And I would like to reiterate that our EPS guidance reflects the performance of the underlying business and is not influenced by our COVID medicines.

謝謝你，馬克。請在這張幻燈片 #35 結束，它說明了我們的新聞流程。我可以得到幻燈片 35 嗎？它說明了未來幾個月整個公司的新聞流。在腫瘤學方面，我們預計明年上半年 HER2 低位乳腺癌的 Enhertu DESTINY-Breast04 試驗數據以及肺癌和宮頸癌的多個 Imfinzi 讀數。在 CVRM 中，我們將獲得 Farxiga 和 HFpEF 的 DELIVER 試驗數據，以及來自 Ultomiris 和 NMOSD 的罕見疾病數據。我們將繼續按計劃提供全年指導。我想重申，我們的每股收益指引反映了基礎業務的表現，不受我們的 COVID 藥物的影響。

We're also excited with the basic clinical news flow ahead. I'm very, very proud of our colleagues' concurring dedication and focus. And the addition of Alexion will increase our commitment to bring transformative medicines to patients around the world.

我們也對未來的基本臨床新聞流感到興奮。我為我們的同事一致的奉獻精神和專注感到非常非常自豪。 Alexion 的加入將增強我們為全球患者帶來變革性藥物的承諾。

Thank you all for joining, and we'll now take the questions.

感謝大家的加入，我們現在將回答問題。

[Slide]36 please. Thank you, Pascal and team. We'll now go to Q&A. (Operator Instructions) Perhaps now we can take the first question from the conference call. Back to you, Pascal.

[幻燈片]36 請。謝謝你，帕斯卡和團隊。我們現在去問答環節。 （操作員說明）也許現在我們可以從電話會議中提出第一個問題。回到你身邊，帕斯卡。

Thank you, Chris. So we'll take -- first question is from James Gordon at JPMorgan. James, go ahead.

謝謝你，克里斯。所以我們將接受——第一個問題來自摩根大通的詹姆斯戈登。詹姆斯，繼續。

James Gordon from JPMorgan. The first question is about 2021 guidance and the implied Q4. So we're about halfway through Q4, but it's an unusually wide guidance remaining, sort of plus or minus 25%. So as things are looking now, is the bottom end of the guidance range still fairly plausible? What would put you in the bottom versus the top for the year? And in terms of sort of spend, normally, Q4 is quite a lot higher on OpEx in Q3 for Astra. So on an underlying basis, ex consolidated more of Alexion, would that normal trend be expected as sort of big step-up in OpEx in Q4 versus Q3? So that's the first question, please.

摩根大通的詹姆斯·戈登。第一個問題是關於 2021 年的指導和隱含的第四季度。所以我們大約在第四季度進行了一半，但這是一個異常廣泛的指導，有點正負 25%。因此，就目前情況而言，指導範圍的底端是否仍然相當合理？是什麼讓你在今年排名墊底而不是頂部？就支出而言，通常情況下，第四季度 Astra 在第三季度的運營支出要高得多。因此，在基本基礎上，合併了更多的 Alexion，這種正常趨勢是否會被預期為第四季度運營支出相對於第三季度的大幅增長？所以這是第一個問題，請。

And the follow-up I'll do now as well, which is just OpEx beyond this year, so what are the moving parts? I can see there's quite a few Phase III initiations planned and some of which you already booked half of and also a bit more promotion. But are there also significant offsets. So for instance, China slowing and other trials completing. So how much of the spend is going to be incremental versus there could be some offsets or some reallocations as we look forward?

我現在也要做的後續行動，這只是今年之後的運營支出，那麼有哪些活動部分？我可以看到計劃了很多第三階段的啟動，其中一些您已經預訂了一半，還有更多的促銷活動。但是否也有顯著的抵消。例如，中國放緩和其他試驗完成。那麼，有多少支出將是增量的，而不是我們期待的一些抵消或一些重新分配？

Thanks, James. So I'll [answer on the] guide in a minute. But let me just make a high-level point here is that our expenses vary quarter-to-quarter. And so we have sometimes high Q3 and a lower Q4, and sometimes vice versa. This year -- or last year, I should say, we had a relatively low Q3 in term of expenses, in particular R&D expenses. And as you can look at, if you look at it for last year, we had an increase in spend in Q4.

謝謝，詹姆斯。所以我會在一分鐘內[回答]指南。但讓我在這裡提出一個高層次的觀點是，我們的費用每個季度都會有所不同。所以我們有時第三季度高，第四季度低，有時反之亦然。今年 - 或者去年，我應該說，我們第三季度的支出相對較低，特別是研發費用。正如您所看到的，如果您查看去年的數據，我們在第四季度的支出有所增加。

And this year, we don't expect that to happen in the same way. So what you have to look at in Q4 is the AV expenses and then, of course, add a full quarter of Alexion expenses and then the COVID R&D expenses on top. But as it relates to AZ, Q4 is going to be a lot -- it's not going to be like previous year where we have an increase in expenses versus Q3. Aradhana, do you want to add more color to this?

今年，我們預計不會以同樣的方式發生這種情況。因此，您必須在第四季度查看 AV 費用，然後當然要加上 Alexion 費用的整整四分之一，然後是 COVID 研發費用。但由於它與 AZ 相關，第四季度將會很多——它不會像去年那樣，我們的費用與第三季度相比有所增加。 Aradhana，你想為此添加更多顏色嗎？

No, I think you covered a number of the aspects. We're reiterating the guidance for the EPS. There is obviously quarter-on-quarter variability. But also fourth quarter will include a full quarter contribution from Alexion, which this quarter was not a full quarter. And then there is some seasonality, as you know, on the top line as well with FluMist and some other products. And generally, we expect fourth quarter revenue to be strong.

不，我認為您涵蓋了許多方面。我們重申對 EPS 的指導。顯然存在季度變化。但第四季度也將包括來自 Alexion 的整個季度的貢獻，而本季度並不是一個完整的季度。如您所知，FluMist 和其他一些產品也有一些季節性因素。一般來說，我們預計第四季度的收入會很強勁。

And then on the expense side, again, some of the elements that Pascal mentioned. So if you think about our fourth quarter and the AZ underlying business, which, again, would be probably more in line with fourth quarter last year, which obviously was different versus third quarter, but -- and then a full quarter of expenses, both the R&D and SG&A from Alexion, plus on top of that, some of these COVID-related expenses where we're investing behind the antibody and the vaccine.

然後在費用方面，再次提到帕斯卡提到的一些要素。因此，如果您考慮我們的第四季度和 AZ 基礎業務，這可能會更符合去年第四季度，這顯然與第三季度不同，但是 - 然後是整個季度的費用，兩者Alexion 的研發和 SG&A，除此之外，還有一些與 COVID 相關的費用，我們在這些費用中投資於抗體和疫苗。

And remember also that the vaccine sales attract pharmacovigilance costs, right? So we get enough margin, a small gross margin that covers those costs. And so we get to 0 profit. We have pharmacovigilance costs, just like everybody else does, and that also affects the R&D line. But the key message is don't expect Q3, Q4 to evolve like last year. And then you can see [that's] why we reconfirm our guidance. Should we move to the next question? Simon Baker of Redburn. Simon?

還要記住，疫苗銷售會吸引藥物警戒成本，對吧？所以我們得到了足夠的利潤，一個可以彌補這些成本的小毛利。所以我們得到0利潤。我們有藥物警戒成本，就像其他人一樣，這也影響了研發線。但關鍵信息是不要指望第三季度、第四季度會像去年那樣發展。然後你會看到[這就是]我們重新確認我們的指導的原因。我們應該轉到下一個問題嗎？ Redburn的西蒙貝克。西蒙？

Firstly, one for you, Pascal. I just wonder, given all the recent developments, if you could give us your latest thoughts on proposed drug pricing reform in the U.S. following the collapse and reemergence of the Democrats' proposals.

首先，給你一個，帕斯卡。我只是想知道，鑑於最近的所有事態發展，在民主黨提議的崩潰和重新出現之後，您是否可以向我們提供您對美國擬議的藥品定價改革的最新想法。

And then secondly, one for Marc on Alexion. One of the things that was touted when the deal was proposed was the much larger geographic footprint of Astra versus Alexion, and I was just wondering if you could give us a time line of when we will start to see revenues for the Alexion portfolio coming through in new territories as they push through the AstraZeneca infrastructure.

其次，馬克在 Alexion 上的一個。提出交易時被吹捧的一件事是 Astra 與 Alexion 相比，其地理足跡要大得多，我只是想知道您能否給我們一個時間表，說明我們何時開始看到 Alexion 投資組合的收入通過在他們推動阿斯利康基礎設施的新領域。

Thanks, Simon. Can I maybe ask Ruud, actually, to comment on the U.S. pricing regulation? And if Dave, you have anything you want to add to what Ruud will say, please feel free. Over to you, Ruud.

謝謝，西蒙。實際上，我可以請 Ruud 對美國的定價法規發表評論嗎？如果戴夫，你有什麼想補充到路德要說的話，請隨意。交給你了，路德。

Yes, of course. And thank you, Simon, for the question. First of all, I think it's fair to say that AstraZeneca is in favor of a potential reform of the U.S. health care. Out of pocket, of course, for too many patients are too high, which will damage the accessibility for patients to get the right medicine at the right time.

當然是。謝謝你，西蒙，這個問題。首先，我認為阿斯利康支持美國醫療保健的潛在改革是公平的。當然，對於太多的患者來說，自掏腰包太高了，這會損害患者在正確的時間得到正確的藥物的可及性。

Equally, I think it's fair to say that some of the legislation is clearly not -- is not favorable for the whole industry. We don't believe that direct negotiations of the governments with individual companies is going to make a lot of sense. But it's also fair to say that there's still a lot in the air at this stage. It's far from final. So let's wait and see how it is evolving.

同樣，我認為可以公平地說，某些立法顯然不是——不利於整個行業。我們認為政府與個別公司的直接談判沒有多大意義。但也可以公平地說，現階段仍有很多懸念。離最終的還很遠。所以讓我們拭目以待，看看它是如何演變的。

We are in active discussions with policymakers and influential politicians in order to bring our arguments in front of them. So let's not speculate too much about the final results. But let's work constructively with each other in order to try to mitigate, as many as possible, the risk potentially we will face as an industry.

我們正在與政策制定者和有影響力的政治家積極討論，以便將我們的論點擺在他們面前。所以我們不要對最終結果進行過多的推測。但是，讓我們彼此建設性地合作，以盡可能多地減輕我們作為一個行業可能面臨的風險。

Thanks, Ruud. Marc?

謝謝，路德。馬克?

Yes. So thank you, for the question on the larger footprint of Alexion. We are already working very actively to establish teams, dedicated teams where Alexion was not present until now. And we are also engaging local regulators to gain program access. So realistically, I believe the first approval could be obtained in the course of 2022. But I would probably see the first revenues to be generated from 2023.

是的。因此，謝謝您提出有關 Alexion 更大足蹟的問題。我們已經在非常積極地努力建立團隊，專門的團隊，Alexion 直到現在還沒有出現。我們還與當地監管機構合作以獲得項目訪問權。所以現實地說，我相信第一個批准可以在 2022 年獲得。但我可能會看到 2023 年產生第一批收入。

Thank you, Marc. Next question is Tim Anderson. Unless, Dave, did you want to pass anything to the U.S., no?

謝謝你，馬克。下一個問題是蒂姆·安德森。除非，戴夫，你想把任何東西傳遞給美國，不是嗎？

Thank you, but I think Ruud covered it.

謝謝，但我認為 Ruud 涵蓋了它。

So next question is from Tim Anderson.

所以下一個問題來自蒂姆安德森。

Just on Alexion, again, and your move into rare diseases specifically. Just your updated thinking and assumptions about competitor products that are coming after Soliris and Ultomiris. So for example, Novartis has iptacopan, an oral product, doing a true head-to-head versus your HER2 product in PNH. I think that reports out mid-2022.

再說一次，就在 Alexion 上，特別是您進入罕見疾病領域。只是您對在 Soliris 和 Ultomiris 之後出現的競爭對手產品的最新想法和假設。例如，諾華的口服產品 iptacopan 與 PNH 中的 HER2 產品進行了真正的正面交鋒。我認為該報告將於 2022 年年中發布。

I'm wondering if you can remind us again what you assumed on competitive threats like that or other products like Roche's crovalimab when you're trying to figure out what Alexion was worth.

我想知道當您試圖弄清楚 Alexion 的價值時，您是否可以再次提醒我們您對此類競爭威脅或其他產品（如羅氏的 crovalimab）的假設。

And then just building on the last question that you got in new geographies. Can you just talk about rollout of Alexion products in China specifically?

然後只是建立在你在新地區得到的最後一個問題的基礎上。您能具體談談亞力兄產品在中國的推出嗎？

So let me take the second question because it's already, in great part, responded to it with a question of Simon. So if we look at the example of China, we have already established a dedicated team locally, and we are engaging local regulators to gain access to the market. We hope to gain approval maybe in the course of 2022, and possibly sell these products from 2023. So I think the general answer that I provided, China could be a good illustration for it.

所以讓我來回答第二個問題，因為它在很大程度上已經用西蒙的問題回答了它。因此，如果我們以中國為例，我們已經在當地建立了專門的團隊，並且我們正在與當地監管機構合作以進入市場。我們希望可能在 2022 年獲得批准，並可能從 2023 年開始銷售這些產品。所以我認為我提供的一般答案，中國可以很好地說明這一點。

Regarding your question on competition, we are aware of the development work done by Novartis on the overall Factor B in PNH and other renal indications. We're also well aware of the work done by Roche with its C5 inhibitor. I mean this is not something that we discovered recently. We were aware of it.

關於您關於競爭的問題，我們知道諾華在 PNH 和其他腎臟適應症中的整體 B 因子方面所做的開發工作。我們也很清楚羅氏利用其 C5 抑製劑所做的工作。我的意思是這不是我們最近發現的。我們意識到了這一點。

We believe Soliris and Ultomiris will remain very strong leaders in their class due to the excellent efficacy, short-term and long-term efficacy in the legacy indication, PNH, atypical HUS, but also in the neurology indication where Soliris is presently indicated and where Ultomiris, as recently, read out very strong Phase III results showing a very rapid onset and durable efficacy over 52 weeks.

我們相信 Soliris 和 Ultomiris 將在同類產品中保持非常強大的領導地位，因為在傳統適應症 PNH、非典型 HUS 以及目前適用於 Soliris 的神經學適應症以及在哪裡Ultomiris 最近公佈了非常強勁的 III 期結果，顯示出非常快速的起效和超過 52 週的持久療效。

So this is the strength of Alexion. We believe we have enough strength to maintain the leadership in this class. The class is going to evolve. There would be competitors entering, but also, Alexion will be moving on to other indications in the future.

這就是Alexion的實力。我們相信我們有足夠的實力保持在這個班級的領先地位。班級將不斷發展。會有競爭對手進入，但亞力兄未來將轉向其他跡象。

Thank you, Marc. Next question is Michael Leuchten, Michael, go ahead.

謝謝你，馬克。下一個問題是 Michael Leuchten，Michael，請繼續。

One follow-up question to your R&D commentary, please. I think last quarter, you talked a little bit to the fact that the COVID-19 R&D was maybe going to come down over time. It sounds like you're now saying this is going to stick around and thinking about your commentary about the vaccine being commercial for next year. Should we assume that an incremental R&D is actually going to run at this sort of level for longer? That's question number one.

請對您的研發評論提出一個後續問題。我認為上個季度，您談到了 COVID-19 研發可能會隨著時間的推移而下降的事實。聽起來你現在說這將繼續存在，並考慮你對明年疫苗商業化的評論。我們是否應該假設增量研發實際上會在這種水平上運行更長時間？這是第一個問題。

And then question number 2 on Tagrisso. I take your comment about Tagrisso in China with the phasing, but can you talk a little bit to the risk that maybe the inventory level is also impacted by a competitor being on the NRDL now since earlier this year. And if that's not a risk, could there be a risk that it's impact to your performance for Tagrisso for the fourth quarter?

然後是關於 Tagrisso 的第 2 個問題。我接受你對泰瑞沙在中國分階段的評論，但你能否談談庫存水平可能也受到今年早些時候以來競爭對手加入 NRDL 的影響的風險。如果這不是風險，是否會影響您在 Tagrisso 第四季度的業績？

Thanks, Michael. I mean the first comment -- the first question about R&D, I think what you need to do each time is look at the quarter and look at what I might call "old AZ" then add Alexion, and for Q3, we had 2 months plus a portion of July. For Q4, we'll have a full quarter of R&D expenses. And then the third piece is the COVID assets.

謝謝，邁克爾。我的意思是第一條評論——關於研發的第一個問題，我認為您每次需要做的是查看季度並查看我可能稱之為“舊 AZ”的內容，然後添加 Alexion，對於第三季度，我們有 2 個月的時間加上七月的一部分。對於第四季度，我們將有整個季度的研發費用。第三部分是 COVID 資產。

And what we said before is still true is that if you look at the COVID R&D spend, you have 2 types. One is pharmacovigilance costs related to distribution of the vaccine. And is true R&D costs, developing the vaccine and the lab. So the first part is directly correlated with the volume of vaccine we deliver. And as you saw at the end of September, we've delivered 1.5 billion doses of vaccine globally and we continue with our deliveries.

我們之前所說的仍然正確的是，如果您查看 COVID 研發支出，您有兩種類型。一是與疫苗分發相關的藥物警戒成本。而且是真正的研發成本，開發疫苗和實驗室。因此，第一部分與我們提供的疫苗量直接相關。正如您在 9 月底看到的那樣，我們已經在全球範圍內交付了 15 億劑疫苗，並且我們將繼續交付。

And of course, the pharma provision costs are linked to this volume of vaccine delivered. They are covered, as I said, by the limited gross margin we get, but they're still -- they're quite substantial. And then next year, you'll have lower volume, because we have new orders. But of course, the pandemic will be behind us, so we'll be talking mostly about boosters and also some deliveries to countries that haven't gone through their first 2 doses.

當然，藥品供應成本與交付的疫苗數量有關。正如我所說，它們被我們獲得的有限毛利率所覆蓋，但它們仍然——它們相當可觀。然後明年，你的數量會減少，因為我們有新訂單。但是，當然，大流行將過去，因此我們將主要談論加強劑以及向尚未接種前 2 劑的國家的一些交付。

So lower doses, and therefore, lower PPV -- pharmacovigilance costs, sorry. And then the R&D is sort of the same is, we're now left with a little bit of R&D costs related to the new vaccine and vaccine, AZD2816 looking at multiple variants of concern. And then also some expenses around the latter, but this will decline. So net-net is R&D expenses for COVID should not be, next year, the same as this year, for sure.

所以較低的劑量，因此，較低的 PPV - 藥物警戒成本，對不起。然後研發是一樣的，我們現在剩下一些與新疫苗和疫苗相關的研發成本，AZD2816正在關注多個關注的變體。然後還有一些圍繞後者的費用，但這會下降。所以 net-net 是 COVID 的研發費用，明年肯定不會和今年一樣。

And if you look at the quarter-to-quarter and dissect this, you would see that our AZ R&D expenses are essentially what you would have expected. But then you have to add Alexion and you had to add COVID. So I don't know, Aradhana, if you want to add to this. And if not, then we'll Dave to cover Tagrisso.

如果您按季度查看並剖析這一點，您會發現我們的 AZ 研發費用基本上是您所預期的。但是隨後您必須添加 Alexion，並且您必須添加 COVID。所以我不知道，Aradhana，如果你想補充一下。如果沒有，那麼我們將戴夫報導 Tagrisso。

Yes. No, Dave, go ahead.

是的。不，戴夫，繼續。

Great. Thanks, Michael, for the question. And I hear the question on competition, but I'm going to also -- I'll answer that, but I want to take the opportunity just to also maybe provide some more color on China since I know there's some questions there.

偉大的。謝謝，邁克爾，你的問題。我聽到了關於競爭的問題，但我也會——我會回答這個問題，但我想藉此機會為中國提供更多色彩，因為我知道那裡有一些問題。

So in Q2, we commented that the frontline demand growth was robust and that inventory did factor into the China sales. And this is pretty typical around the NRDL timing, right? Obviously, the inventory levels get drawn down in anticipation of a price reduction. And so we saw, now in Q3, that frontline demand remains strong. The second line share has been resilient. And right now, inventory levels are consistent with the historical patterns.

所以在第二季度，我們評論說一線需求增長強勁，庫存確實影響了中國的銷售。這在 NRDL 時間安排上非常典型，對吧？顯然，庫存水平因預期價格下降而下降。所以我們看到，現在在第三季度，一線需求仍然強勁。二線份額一直保持彈性。目前，庫存水平與歷史模式一致。

I mentioned this in the prepared remarks, but we did also see and we see this now that we did get a onetime benefit from some first-generation TKI switches in the frontline setting in the second quarter, and that was onetime. And so those didn't carry into Q3. But with that said, we expect volume growth to offset the significant price reduction that we took just only 6 months ago. And we would expect that to happen in the months ahead. And that from then, top-line growth will kick in at that point.

我在準備好的評論中提到了這一點，但我們確實也看到了這一點，現在我們看到了這一點，我們確實在第二季度的前線設置中從一些第一代 TKI 交換機中獲得了一次性利益，那是一次。所以那些沒有進入第三季度。但話雖如此，我們預計銷量增長將抵消我們僅在 6 個月前採取的大幅降價措施。我們預計這將在未來幾個月內發生。從那時起，收入增長將在那時開始。

On your question specifically on competition, it's obviously a pretty dynamic marketplace here. There's lots of new competitors that are entering. Right now, as I said, the frontline penetration that we're making is robust. Second line has been resilient. We do know that NRDL is in the midst of going on. We know that in the fourth quarter in China, there is some hospital capping that takes place. So China does remain dynamic. But in terms of the things that we can control, I think that the demand numbers are moving in the right direction and give us confidence that we're driving access into the populations where we've got now in our deal inclusion.

關於你關於競爭的問題，這裡顯然是一個非常活躍的市場。有很多新的競爭對手正在進入。現在，正如我所說，我們正在進行的前線滲透是強大的。二線一直有彈性。我們確實知道 NRDL 正在進行中。我們知道，在中國第四季度，出現了一些醫院上限。所以中國確實保持活力。但就我們可以控制的事情而言，我認為需求數字正在朝著正確的方向發展，這讓我們相信，我們正在推動進入我們現在在我們的交易包容性中獲得的人群。

Thanks, Dave. The volume growth for Tagrisso in China is very substantial. So as soon as we've washed out the price effect, we should see some growth next year. Sachin, Bank of America. Sachin, go ahead.

謝謝，戴夫。 Tagrisso 在中國的銷量增長非常可觀。因此，一旦我們消除了價格效應，明年我們應該會看到一些增長。薩欽，美國銀行。薩欽，繼續。

I'm not sure I quite followed that. I think I understood, Pascal, you said fourth quarter wouldn't see the usual pickup. Aradhana then said that the Astra, underlying, will be flat year-on-year. If I take last year's fourth quarter SG&A and R&D being in line, add on Alexion, that still points to sequential cost growth versus numbers you print for the third quarter. So I just want to be crystal clear on that interpretation.

我不確定我是否完全遵循了這一點。我想我明白了，帕斯卡，你說第四季度不會看到通常的回升。 Aradhana 然後表示，底層的 Astra 將與去年同期持平。如果我認為去年第四季度的 SG&A 和研發是一致的，再加上 Alexion，這仍然表明連續成本增長與第三季度打印的數字相比。所以我只想對這種解釋一清二楚。

And given that variability, third quarter to fourth quarter with third quarter high growth, fourth quarter were flattish, what's the best indicator of cost growth into '22, please? So that's question one.

鑑於這種可變性，第三季度到第四季度第三季度高增長，第四季度持平，請問到 22 年成本增長的最佳指標是什麼？所以這是問題一。

Question 2 is just shorter and simpler. On Lynparza, Dave, we discussed a number of scenarios in 2Q on the data strength being wild-type and prior [ADT] failures, where within that spectrum has the data landed and obviously, going to hit an all-comers? But any color on the strength and confidence in that being a multibillion opportunity?

問題 2 更短更簡單。在戴夫的 Lynparza 上，我們在第二季度討論了一些關於數據強度為野生型和先前 [ADT] 故障的場景，在該頻譜範圍內，數據在哪裡登陸，並且顯然會打擊所有參與者？但是，對於這是一個數十億機會的實力和信心有何影響？

So Sachin, we -- I mean, we don't give guidance quarter-to-quarter. But I think your assumption is -- your assumption of building Q4 in line with Q3 for AZ and then Alexion and COVID on top is a fair one. For both R&D and SG&A, I think it's fair. Aradhana, anything you want to say on this one as well?

所以薩欽，我們 - 我的意思是，我們不會按季度提供指導。但我認為你的假設是——你假設 AZ 的 Q4 與 Q3 一致，然後是 Alexion 和 COVID 是一個公平的假設。對於 R&D 和 SG&A，我認為這是公平的。 Aradhana，關於這個，你也有什麼想說的嗎？

No. I think for fourth quarter, again, we've not given guidance per se. But the building blocks are what we mentioned, which is if you look at fourth quarter AZ underlying for last year, you look at the Alexion fourth quarter, which will be a full quarter and then additional expenses relating to the COVID product.

不，我認為第四季度，我們本身並沒有給出指導。但是構建模塊就是我們提到的，如果你看去年第四季度的 AZ，你看看 Alexion 第四季度，這將是一個完整的季度，然後是與 COVID 產品相關的額外費用。

And the second question, anything you want to add? Sorry, go ahead. Go ahead, Aradhana.

第二個問題，你想補充什麼？對不起，繼續。來吧，阿拉達納。

No, no, that was for Dave.

不，不，那是給戴夫的。

Yes. The second question from Sachin was on PROpel. And, I mean, I think, Sachin, on this, a couple of things. I mean, obviously, at this point, we've only shared the high-level results. And we'll have to present the data at an upcoming meeting, I think. So within that, I'm not going to give too much insight into how we're feeling about the full results. I think we've got to let that continue to get analyzed and worked through.

是的。 Sachin 的第二個問題是關於 PROpel。而且，我的意思是，我認為，薩欽，在這方面，有幾件事。我的意思是，顯然，在這一點上，我們只分享了高層次的結果。我認為，我們必須在即將召開的會議上展示數據。因此，在此範圍內，我不會過多地深入了解我們對完整結果的感受。我認為我們必須讓它繼續得到分析和解決。

But I think, just to reiterate some of the things that we talked about last time. If approved, PROpel is a blockbuster plus opportunity. There are a handful of variables, data and regulatory that going are to affect, I think, the ultimate size of the opportunity. The whole market is obviously quite large in terms of the frontline metastatic castrate-resistant prostate cancer.

但我想，只是重申一下我們上次談到的一些事情。如果獲得批准，PROpel 將是一個重磅炸彈和機會。我認為，有一些變量、數據和監管將影響機會的最終規模。就一線轉移性去勢抵抗性前列腺癌而言，整個市場顯然是相當大的。

I think that the things that we're going to have to learn more about as we share these data is class share is going to be impacted by the fact that, first, remember the PARP combination treatment in this setting is an entirely new approach to the treatment of these patients. I think that physicians, and we've got both urologists as well as medical oncologists, are going to take a look at the magnitude of the rPFS benefit in ITT. They're also likely going to want to look at HR mutants as well as wild type. I think that they'll consider prior NHA status.

我認為，當我們共享這些數據時，我們必須更多地了解的事情是班級共享將受到以下事實的影響：首先，請記住，在這種情況下，PARP 組合治療是一種全新的方法這些病人的治療。我認為醫生，我們既有泌尿科醫師也有腫瘤內科醫師，將看看 ITT 中 rPFS 獲益的幅度。他們也可能想要查看 HR 突變體和野生型。我認為他們會考慮之前的 NHA 狀態。

And then obviously, there's quite a bit of competition with 4 or 5 competitors. So there's a lot of variables that are at play. So it's a big, meaningful market, blockbuster plus. And I think that as we get to see more of the data and share more of it with clinicians and obviously with health authorities, we'll have the ability to help further refine and help with where the modeling is.

然後很明顯，與 4 或 5 個競爭對手的競爭相當激烈。所以有很多變數在起作用。所以這是一個大而有意義的市場，一鳴驚人。而且我認為，隨著我們看到更多數據並與臨床醫生共享更多數據，顯然與衛生當局共享，我們將有能力幫助進一步完善和幫助建模的位置。

Okay. I wonder if Aradhana wants to comment at all. I mean, not providing guidance but just on cost growth trends into '22, what's the best predictor of a 3Q trend or a 4Q trend?

好的。我想知道阿拉達納是否想發表評論。我的意思是，不提供指導，而只是提供 22 年的成本增長趨勢，什麼是 3Q 趨勢或 4Q 趨勢的最佳預測指標？

This one question, I think -- well, go ahead, Aradhana.

我認為這是一個問題——好吧，繼續吧，阿拉達納。

We'll provide guidance for 2022 when we provide the full year results.

當我們提供全年結果時，我們將提供 2022 年的指導。

Next question is Steve Scala at Cowen.

下一個問題是 Cowen 的 Steve Scala。

I have a couple of questions, and I apologize for another Q4 question. But you were asked a couple of times about the wide Q4 EPS range implied in the full year guidance. What are the biggest uncertainties over the next 6 weeks that are creating the inability to narrow the range at this time?

我有幾個問題，對於另一個 Q4 問題，我深表歉意。但你被問過幾次關於全年指導中隱含的廣泛的第四季度每股收益範圍。在接下來的 6 週內，目前無法縮小範圍的最大不確定性是什麼？

Or is it that the company knows exactly where it is headed within the range, but you're just not choosing to change the prior guidance? I assume if you were headed for the low end of the EPS range that you would have told us that today. And then a second question for Dave. What percent of U.S. Tagrisso sales go through Medicare Part D?

還是公司確切地知道它在該範圍內的發展方向，但您只是沒有選擇更改先前的指導？我假設如果你正走向每股收益範圍的低端，你今天會告訴我們的。然後是 Dave 的第二個問題。美國 Tagrisso 銷售額的百分之幾通過 Medicare D 部分？

Thanks, Steve. I mean your assumption is fair, and we are absolutely on track. There's no concern on our side as it relates to our guidance. We didn't narrow it. I mean, maybe Aradhana wants to cover this, but we thought we'd stick to what we have in the half year. There was no specific reason or concern. Aradhana, do you want to address this?

謝謝，史蒂夫。我的意思是你的假設是公平的，我們絕對走上正軌。我們這邊沒有任何顧慮，因為這與我們的指導有關。我們沒有縮小範圍。我的意思是，也許 Aradhana 想要報導這一點，但我們認為我們會堅持半年的內容。沒有具體的原因或擔憂。 Aradhana，你想解決這個問題嗎？

Yes. I mean generally, we give guidance for the year. This year, we updated the guidance in the close of Alexion, given that was a major transaction. But other than that, I think we're reconfirming guidance. And we don't want to give sort of every quarter further updates.

是的。我的意思是，一般來說，我們會為這一年提供指導。今年，鑑於這是一項重大交易，我們在 Alexion 收盤時更新了該指引。但除此之外，我認為我們正在重新確認指導。而且我們不想在每個季度都提供進一步的更新。

Yes. And we are on track. I mean, Steve, there's really no concern that made us -- I mean that drove our decision. It was just sticking to what we had said half year. I mean we're absolutely on track. Dave, do you want to cover the second question?

是的。我們正在走上正軌。我的意思是，史蒂夫，真的沒有什麼讓我們擔心——我的意思是這推動了我們的決定。它只是堅持我們所說的半年。我的意思是我們完全走上了正軌。戴夫，你想回答第二個問題嗎？

Yes. Pascal, can you just come back to me on that one. I want to make sure I get Steve the right one on this. And so can we just come back?

是的。帕斯卡，你能不能就那個問題回來找我。我想確保我讓史蒂夫在這件事上是正確的。那麼我們可以回來嗎？

How much U.S. Tagrisso sales on Medicare part D?

Medicare D 部分在美國的 Tagrisso 銷售額是多少？

I understood the question. I need to just come back on the answer to it. Can we come back just right after the next one?

我明白了這個問題。我需要回到它的答案。我們可以在下一個之後馬上回來嗎？

Sorry, so we'll come back to it a bit later. So next question is Andrew Baum with Citi.

抱歉，我們稍後再討論。下一個問題是花旗的 Andrew Baum。

Question to Susan and then one for Dave. So Susan, could you talk to your confidence on the bystander effect being clinically significant and how dependent is the outcome of DESTINY-Breast04 on that given a sort of heterogeneous patient population?

向蘇珊提問，然後向戴夫提問。那麼，蘇珊，您能否談談您對旁觀者效應在臨床上具有顯著意義以及 DESTINY-Breast04 的結果對給定一種異質患者群體的依賴性有多大的信心？

And then second for Dave. Just following on from the conversations about U.S. drug pricing proposals, and I completely understand that there's a significant uncertainty between what is circulating and what may ultimately get passed. But taking what has been proposed as the final outcome, how should we think about the potential risk to Tagrisso from lower-price entrants? And I'm thinking of almonertinib.

然後是戴夫。繼關於美國藥品定價提案的對話之後，我完全理解在流通的內容和最終可能通過的內容之間存在很大的不確定性。但以所提出的結果為最終結果，我們應該如何看待低價進入者對泰瑞沙的潛在風險？我在考慮almonertinib。

If the PBMs are now on the hook for 60% of catastrophic coverage, do you anticipate that, that would precipitate widespread use of step edits, prioritization, the like that could exert a significant downward effect on volume or pricing for Tagrisso within the Medicare Part D segments of the U.S.?

如果 PBM 現在要承擔 60% 的災難性覆蓋，您是否預計這會導致步驟編輯、優先級排序等的廣泛使用，這可能會對醫療保險部分中 Tagrisso 的數量或定價產生顯著的下行影響美國的D段？

So I can take the first question. Thanks, Andrew. So I do think the bystander effect is important. The basic design of the molecule is to have a link that is stable in the peripheral circulation and cleavable in the tumor microenvironment. We've shown that, that makes a difference preclinically.

所以我可以回答第一個問題。謝謝，安德魯。所以我確實認為旁觀者效應很重要。該分子的基本設計是具有在外周循環中穩定且在腫瘤微環境中可切割的鏈接。我們已經證明，這在臨床前會有所不同。

And I think the totality of data across the Enhertu program, not just from the J101 data, which was in low HER2 breast cancer, we showed activity beyond what you have seen with ADCs like TDM-1 that don't have that kind of cleavable link that judge a bystander effect.

而且我認為整個 Enhertu 計劃的全部數據，不僅僅是來自低 HER2 乳腺癌的 J101 數據，我們展示的活動超出了你在 TDM-1 等不具有那種可切割性的 ADC 中看到的活動判斷旁觀者效應的鏈接。

It's not just the low HER2 breast cancer data and the DBO3 high HER2 breast cancer data, but across the totality of the program in a range of tumors that have lower HER2 expression than the highly amplified. You're seeing a range of activities beyond what you would have expected from prior designed ADCs. So I think that does underpin the confidence in the design of a DBO4, and we look forward to seeing the data in the early part of next year.

不僅是低 HER2 乳腺癌數據和 DBO3 高 HER2 乳腺癌數據，而且在整個項目中，HER2 表達低於高度擴增的一系列腫瘤。您看到的一系列活動超出了您對先前設計的 ADC 的預期。所以我認為這確實增強了對 DBO4 設計的信心，我們期待在明年年初看到數據。

Thanks, Susan.

謝謝，蘇珊。

So thank you, Andrew, on the question. Let me also just start on Steve's question. Part D represents 20% of the U.S. Tagrisso business. And it's relevant, obviously, to the question that Andrew, you asked as well.

所以謝謝你，安德魯，關於這個問題。讓我也從史蒂夫的問題開始。 D 部分代表美國 Tagrisso 業務的 20%。顯然，這與你提出的安德魯的問題有關。

I mean, I think, Andrew, on this particular piece, that certainly, the resolve of plans to try to put into place mechanisms to manage their share of catastrophic will unlikely be emboldened by the increased percentage if it goes through as it's said. I still think that it's important to keep in mind that, one, almo needs to be able to get approved in the United States with single-arm -- I mean, sorry, with a different comparator arm. We don't know where OS is going to net out, and obviously, a China-only study.

我的意思是，我認為，安德魯，在這個特定的部分，當然，如果它按照所說的那樣通過增加的百分比，那麼嘗試建立機制來管理他們的災難份額的計劃的決心不太可能受到鼓舞。我仍然認為重要的是要記住，一個，almo 需要能夠通過單臂在美國獲得批准——我的意思是，對不起，使用不同的比較臂。我們不知道 OS 將在哪裡進行，顯然，這是一項僅限中國的研究。

And I also think that physician prescribing preferences, as it relates to that clinical benefit that we -- or clinical strength that we see right now, does remain to be an important area of influence. So we'll have to see exactly how it plays out. But I think that those are the ways that we're thinking about it right now.

而且我還認為，醫生的處方偏好，因為它與我們的臨床益處——或我們現在看到的臨床強度有關，仍然是一個重要的影響領域。所以我們必須看看它到底是如何發揮作用的。但我認為這些是我們現在正在考慮的方式。

Thanks, Dave. Mark Purcell is the next question.

謝謝，戴夫。馬克·珀塞爾是下一個問題。

Pascal, the question is on investment discipline supporting the industry-leading pipeline. You've got a clearly, a very broad set of organic opportunities in front of you, and you mentioned the potential for BD. So just sort of in general, Pascal, given you've sort of given us, in the past, sort of AstraZeneca underlying revenue growth, ex vaccine, have double digit, should we also be expecting R&D growth to support that being roughly double-digit growth going forward?

帕斯卡，問題在於支持行業領先管道的投資紀律。擺在您面前的顯然是一系列非常廣泛的有機機會，並且您提到了 BD 的潛力。所以一般來說，帕斯卡，考慮到你在過去給我們提供了阿斯利康的基本收入增長，前疫苗，有兩位數，我們是否也期望研發增長支持大約雙-未來的數字增長？

And then secondly, to the -- some of the products where there's been updates. Could you sort of help us understand next steps now for the cotadutide and PCSK9 molecules, whether they're going to jump into Phase III, yes or no?

其次，對於一些有更新的產品。您能否幫助我們了解 cotadutide 和 PCSK9 分子的下一步，它們是否會進入 III 期，是或否？

And then for the MPO, you mentioned you're now going to start a Phase IIb, Phase III. And clearly, that could be a very complementary molecule alongside Farxiga potentially a combination molecule. So maybe, Mene, if you could tell us sort of what the plans are for 4831, that would be really useful.

然後對於 MPO，您提到您現在將啟動 IIb 階段、III 階段。很明顯，這可能是一個非常互補的分子，與 Farxiga 一起可能是一個組合分子。所以也許，Mene，如果你能告訴我們 4831 的計劃是什麼，那將非常有用。

Thanks, Mark. I mean the R&D expense, whatever we said before, we've said before that it would be in the low 20s, 20, maybe a little bit more than 20, but around that kind of number over time. That's the kind of spend that I think we need to maintain. And of course, we need to have the projects. If we don't have the projects, we'll reduce. But we tend these days to have more projects than we can fund. So we cut the R&D spend, and we prioritize. And it's sometimes painful, but we do prioritize heavily.

謝謝，馬克。我的意思是研發費用，不管我們之前說什麼，我們之前說過，它會在 20 多歲、20 多歲，也許比 20 多一點，但隨著時間的推移，大約是這個數字。我認為我們需要維持這種支出。當然，我們需要有項目。如果我們沒有項目，我們就會減少。但如今，我們傾向於擁有比我們能夠資助的更多的項目。所以我們削減了研發支出，並優先考慮。這有時很痛苦，但我們確實很重視。

And we've said that what we're going to do is, over time, reduce SG&A, and that hasn't changed, and we continue working on this. You saw in Q3, we have more leverage. Of course, Q3, Q4, I think there's a cannibalization issue of expenses that maybe not everybody had really considered. But overall, we continue driving operational leverage, and that will continue to happen with an SG&A spend as a percentage of sales that reduces. On the other question, Mene, do you want to cover this one?

我們已經說過，隨著時間的推移，我們要做的是減少 SG&A，這並沒有改變，我們將繼續努力。你在第三季度看到，我們有更多的籌碼。當然，第三季度，第四季度，我認為可能不是每個人都真正考慮過費用的蠶食問題。但總的來說，我們繼續推動運營槓桿，這將繼續發生，因為 SG&A 支出佔銷售額的百分比下降。關於另一個問題，Mene，你想討論這個問題嗎？

Yes. I mean I can say that cotadutide data will be presented soon. The PCSK9 data, we haven't had. I mean, all of these programs have met the go criteria for moving. As Pascal said, that they've all got to be reviewed and prioritized and go to governance, and then we have to formally make the Phase III investment decision based on the business case and the opportunity.

是的。我的意思是我可以說很快就會提供 cotadutide 數據。 PCSK9 數據，我們沒有。我的意思是，所有這些程序都符合移動的標準。正如 Pascal 所說，它們都必須經過審查和優先排序並進行治理，然後我們必鬚根據業務案例和機會正式做出第三階段的投資決策。

So whilst we have, I think, the data set to move to Phase III, we also need to have the business case to move to Phase III as well, and they have to stack up against other opportunities that we have. But that would probably be all I have to say from a biopharma perspective.

因此，我認為，雖然我們擁有進入第三階段的數據集，但我們還需要擁有進入第三階段的商業案例，並且它們必須與我們擁有的其他機會相結合。但從生物製藥的角度來看，這可能就是我要說的。

And Mene, on the 4831 product, the MPO, could you help us understand what the plans are for that?

Mene，關於 4831 產品 MPO，您能否幫助我們了解這方面的計劃？

It's an integrated program. So we'll have interims obviously. And if we meet the interim analysis criteria, then we'd move into the Phase III part of the study.

這是一個綜合程序。所以我們顯然會有臨時的。如果我們符合中期分析標準，那麼我們將進入研究的第三階段。

Thank you, Mark. The next question is Richard Parkes, and we'll try to keep our responses short. Richard, over to you.

謝謝你，馬克。下一個問題是 Richard Parkes，我們會盡量簡短地回答。理查德，交給你了。

So firstly, I recall the post -- a call post announcement of the Alexion acquisition, Marc, I would ask if you're comfortable around the trajectory of consensus, AstraZeneca top line and margins through the deal. And you stated that, in fact, internal planning assumptions suggested upside to that. And for that reason, I think consensus has assumed an uplift in margins next year and then improvement thereafter.

因此，首先，我記得那個帖子——關於收購 Alexion 的電話公告，馬克，我想問你是否對達成共識的軌跡、阿斯利康的頂線和通過交易的利潤感到滿意。你說，事實上，內部規劃假設暗示了這一點。出於這個原因，我認為共識已經假設明年利潤率會上升，然後會有所改善。

I just wonder if Marc's comment on underlying margin assumptions still stands or, if anything, has changed over the last 12 months, even there's pressure from VBP or simply a desire to invest to a greater degree and might depress profitability. And so that's the first question.

我只是想知道馬克對潛在利潤率假設的評論是否仍然有效，或者，如果有的話，在過去的 12 個月中是否發生了變化，即使存在來自 VBP 的壓力，或者只是希望進行更大程度的投資，並可能壓低盈利能力。這是第一個問題。

The second is just on China VBP headwinds next year. You've obviously now got visibility on what products are going to be impacted. I wondered if you would be willing to quantify what kind of headwinds you'd expect in 2022?

第二個是明年中國 VBP 的逆風。您現在顯然已經了解了哪些產品將受到影響。我想知道您是否願意量化您預計 2022 年會遇到什麼樣的逆風？

Aradhana, do you want to cover the first one? And Leon could cover the second one.

Aradhana，你想覆蓋第一個嗎？萊昂可以覆蓋第二個。

Yes. I think the first one is really around -- the question is one of operating leverage, and we're always focused on improving our operating leverage, balanced obviously with investment in the business. And as Pascal, you heard him, and I'm sure my R&D colleagues will attest, that we have more projects than we can fund. And then there's always some quarter-on-quarter variability.

是的。我認為第一個問題確實存在 - 問題是運營槓桿，我們一直專注於提高我們的運營槓桿，顯然與業務投資保持平衡。作為帕斯卡，你聽到了他的話，我相信我的研發同事會證明，我們的項目比我們能資助的要多。然後總是存在一些季度變化。

But our ambition is to be at sort of the 30% plus for the base business and Alexion on top. Alexion will now, going forward, obviously, is part of our core business. And our mix shift in terms of the specialty versus primary care will continue to evolve. And where we see margins going will depend on how that mix evolves, which of our programs are more successful. And you know we also have some partnered programs, which have lower margins. But our ambition is -- continues to be the same, and we are very much focused on operating leverage. I think there were some R&D questions for Mene.

但我們的目標是在基礎業務和 Alexion 上達到 30% 以上。顯然，Alexion 現在將成為我們核心業務的一部分。我們在專科與初級保健方面的組合轉變將繼續發展。我們看到利潤的去向將取決於這種組合如何演變，我們的哪些項目更成功。你知道我們也有一些合作項目，它們的利潤率較低。但我們的目標是——繼續保持不變，我們非常關注運營槓桿。我認為梅內有一些研發問題。

No, it was a VBP question for China.

不，這是針對中國的 VBP 問題。

Yes. So regarding VBP for 2022, I think the batch 6 this year is still insulin. And there could be coming, first half of next year, batch 7. And one of our major products, I think, Seloken ZOK, could potentially be impacted next year. But based on our past experience, VBP tender, we usually will not win the tender, and we get a 20% to 30% price cut and lose some volume and then maintaining a majority of the loyal patients.

是的。所以關於 2022 年的 VBP，我認為今年的第 6 批仍然是胰島素。明年上半年可能會出現第 7 批。我認為，我們的主要產品之一 Seloken ZOK 可能會在明年受到影響。但是根據我們以往的經驗，VBP 招標，我們通常不會中標，我們會降價 20% 到 30% 並損失一些數量，然後保持大部分的忠實患者。

So I think -- and gradually, the sales is flattening out. So I think there's impact. I think the largest impact next year will be Pulmicort VBP impact, actually happened already in October this year so -- and will continue to have impact on Pulmicort business.

所以我認為 - 銷售逐漸趨於平緩。所以我認為有影響。我認為明年最大的影響將是 Pulmicort VBP 影響，實際上已經在今年 10 月發生了——並且將繼續對 Pulmicort 業務產生影響。

Thanks, Leon. I mean the [time of] VBP, which are the impact -- I mean, we've had quite a number of products affected this year, which affect this year and next year. But in terms of new batches, as Leon explained, next year, this -- we are much less affected, fewer products. I mean Seloken is really the main one. So the next question is Mattias Häggblom.

謝謝，萊昂。我的意思是 VBP 的 [時間]，這是影響 - 我的意思是，今年我們有相當多的產品受到影響，今年和明年都會受到影響。但就新批次而言，正如 Leon 解釋的那樣，明年，我們受到的影響要小得多，產品也會更少。我的意思是塞洛肯確實是主要的。所以下一個問題是 Mattias Häggblom。

Mattias Häggblom, Handelsbanken. I have 2. So with a public offer for Sobi, where AstraZeneca has an 8% shareholding and roughly a $640 million position, and given the acceptance period had now been extended twice, I'm not sure I've seen AstraZeneca's view of the offer.

Mattias Häggblom，德國商業銀行。我有 2 個。因此，對於 Sobi 的公開報價，阿斯利康擁有 8% 的股權和大約 6.4 億美元的頭寸，鑑於接受期現已延長兩次，我不確定我是否看到了阿斯利康對提供。

And tied to this, and given your recent acquisition of Alexion, can you remind me if this is a strategic position or a financial one? And then secondly, with 2 antivirus for COVID close to be rolled out in the marketplace, can you talk about what role you think the antibody cocktails, including long-acting prophylaxis, will play in light of these recent developments?

與此相關，鑑於您最近收購了 Alexion，您能提醒我這是戰略地位還是財務地位？其次，隨著 2 款針對 COVID 的抗病毒藥物即將在市場上推出，您能否談談您認為抗體雞尾酒（包括長效預防）將在這些近期發展中發揮什麼作用？

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

Aradhana，你想拿第一個，Mene 拿第二個嗎？

Yes. So we can't really and don't really comment on our financial positions. So we can't really comment on your Sobi question.

是的。所以我們不能真的也不會真的評論我們的財務狀況。因此，我們無法真正評論您的 Sobi 問題。

Can I just make sure I understood the question that you asked about. I wasn't sure if you're asking a question about the vaccine and the antibody or just the antibody. Can you just repeat the question, please, Mattias?

我能確保我理解你問的問題嗎？我不確定您是在問關於疫苗和抗體的問題，還是只是關於抗體的問題。馬蒂亞斯，你能重複一下這個問題嗎？

Sure, Mene. So I was wondering if the view of the long-acting prophylactic antibodies is now seen in a different light given the recent development of some polymerase and protease inhibitors.

當然，梅內。所以我想知道，鑑於最近一些聚合酶和蛋白酶抑製劑的發展，現在是否可以從不同的角度看待長效預防性抗體的觀點。

Not at all. Not at all. I mean again, I'll put it -- I'll try and articulate it reasonably. About 2% of the population, 2% to 3% don't respond adequately to vaccines, cancer patients, hematological malignancies, transplant patients, people on chronic immunosuppression, right? We can wait for them to get sick and then have somewhere between a 50% and 80% protection from severe disease. And so they stay locked up and don't go out at all, or you can give them a single injection and protect them for a year from getting any symptoms. I know what I'd rather have.

一點也不。一點也不。我再說一遍，我會說——我會嘗試合理地表達它。大約 2% 的人口，2% 到 3% 對疫苗、癌症患者、血液系統惡性腫瘤、移植患者、慢性免疫抑制患者沒有充分反應，對嗎？我們可以等待他們生病，然後在 50% 到 80% 之間獲得對嚴重疾病的保護。所以他們一直被關起來，根本不出去，或者你可以給他們注射一次，保護他們一年不出現任何症狀。我知道我寧願擁有什麼。

We're not going to protect those people with -- using tablets every month or every week or so, right? So totally different use. Next one is Matt Weston of Credit Suisse.

我們不會用每個月或每週左右使用平板電腦來保護這些人，對吧？所以完全不同的用途。下一位是瑞士信貸的馬特韋斯頓。

Two questions, please. The first for Dave on Tagrisso in the U.S. I'm mindful of your comments. Patient diagnosis from COVID, only 10% light of pre-COVID levels. You mentioned already seeing an impact of increasing treatment duration. And you're stressing that adjuvant is only a modest 20% of frontline patients. So given those, can you just help map out how we should look at Tagrisso, particularly in the U.S. market evolving over the coming years? I think consensus expectations bake in quite meaningful growth, but it suggests from your comments that maybe we shouldn't.

請教兩個問題。 Dave 在美國的 Tagrisso 上的第一個我注意到你的評論。來自 COVID 的患者診斷，僅為 COVID 前水平的 10%。您提到已經看到增加治療持續時間的影響。你強調的是，輔助治療僅佔一線患者的 20%。因此，鑑於這些，您能否幫助制定出我們應該如何看待 Tagrisso，特別是在未來幾年不斷發展的美國市場中？我認為共識預期會帶來非常有意義的增長，但從您的評論中可以看出，也許我們不應該這樣做。

And then the second is a question for Aradhana. Specifically, Merck, in its 10-Q at the third quarter, said it has set aside $400 million for payments to you on Lynparza. Can you let us know what you're assuming will be booked in 4Q of those $400 million?

然後第二個問題是給 Aradhana 的。具體來說，默克在其第三季度的 10-Q 中表示，它已撥出 4 億美元用於在 Lynparza 上向您付款。您能否告訴我們您假設在這 4 億美元中的第四季度會預訂什麼？

So on U.S. Tagrisso, I think that the first element is that as we look at where we are right now, I think that we're -- we do continue to see rising frontline duration of treatment. I think that this is a source of growth moving forward and something that is important. I think secondly, certainly am optimistic that the COVID effects will wash themselves out here at some point in the not-too-distant future. I think that the key and core element in the U.S. is the ADAURA population. While the NRx contribution to our TRx is -- at the moment right now is relatively modest and I think, in many respects, being offset by the COVID declines, the duration of therapy that we would expect somewhere between 2 and 3 years does really begin to, over time, add up.

所以關於美國泰瑞沙，我認為第一個要素是，當我們看看我們現在所處的位置時，我認為我們 - 我們確實繼續看到一線治療持續時間增加。我認為這是向前發展的源泉，也是很重要的事情。其次，我認為，在不久的將來，COVID 的影響會在某個時候消失，這當然是樂觀的。我認為美國的關鍵和核心要素是 ADAURA 人口。雖然 NRx 對我們的 TRx 的貢獻是——目前相對溫和，我認為，在許多方面，被 COVID 下降所抵消，我們預計 2 到 3 年之間的治療持續時間確實開始了到，隨著時間的推移，加起來。

So I think from a peak year perspective, when we take a look at adjuvant, as we continue to move the key performance indicators, which is we continue to move testing rates, continue to move referrals, continue to move adjuvant treatment utilization, and as we get the TRx growth, I think that we're going to see peak year have good opportunities for growth. I think it's just the time that it's going to take to get there may be a little longer than some folks were anticipating given the speed with which we penetrated into the frontline metastatic space.

因此，我認為從高峰年的角度來看，當我們查看輔助治療時，隨著我們繼續移動關鍵績效指標，即我們繼續移動檢測率，繼續移動轉診，繼續移動輔助治療利用率，以及我們得到了 TRx 的增長，我認為我們將看到高峰年有很好的增長機會。考慮到我們進入一線轉移空間的速度，我認為到達那裡所需的時間可能比一些人預期的要長一些。

Thanks, Dave. Aradhana, will you cover the first one?

謝謝，戴夫。 Aradhana，你會介紹第一個嗎？

Yes. So on your specific question, we don't give specifics around milestones and -- but that is the arrangement, as you know, that we have with Merck and that will reflect as the milestones earned in our estimates.

是的。因此，關於您的具體問題，我們沒有提供有關里程碑的具體信息，但正如您所知，這就是我們與默克公司的安排，這將反映在我們的估計中獲得的里程碑。

Next question is Emmanuel Papadakis.

下一個問題是 Emmanuel Papadakis。

Emmanuel Papadakis from Deutsche Bank. Maybe take a couple on the Deutsche collaboration assets. So datopotamab, I noticed, probably on Lung01 was not listed as a 2022 readout. So is that now more likely '23?

德意志銀行的 Emmanuel Papadakis。也許在德意志合作資產上拿幾個。所以我注意到 datopotamab 可能在 Lung01 上沒有被列為 2022 年的讀數。那麼現在更有可能是 23 年嗎？

More importantly, you announced the initiation of TROPION-Lung08 in PD-L1 high with KEYTRUDA. So just interested in the rationale for that, why PD-L1 high, why choose KEYTRUDA over Imfinzi? And how do you see that sitting with TIGIT, for example, where you also obviously have an active clinical development program?

更重要的是，您宣布與 KEYTRUDA 一起在 PD-L1 high 啟動 TROPION-Lung08。所以只是對其基本原理感興趣，為什麼 PD-L1 高，為什麼選擇 KEYTRUDA 而不是 Imfinzi？例如，您如何看待與 TIGIT 坐在一起的情況，您顯然也有一個積極的臨床開發計劃？

And then maybe just a couple very short ones on Enhertu. Could you just give us an update on your adjuvant planned season? You did mention the lack of significant ILD being encouraging for earlier line use earlier. You're yet still to announce anything in adjuvants. And could you just clarify your perspective in the extent of your potential exposure to the outcome of the Seagen-DS litigation? Are you ringfenced from that? Or does that remain to be determined?

然後可能只是 Enhertu 上的幾個非常短的。你能告訴我們你的輔助計劃賽季的最新情況嗎？您確實提到了缺乏重要的 ILD，這對早期的早期生產線使用是令人鼓舞的。你還沒有宣布任何佐劑。您能否澄清您對 Seagen-DS 訴訟結果的潛在風險程度的看法？你是不是被這個圈套了？還是還有待確定？

Thanks, Emmanuel. So maybe, Susan, you could cover the first one and Dave the second one.

謝謝，伊曼紐爾。所以也許，蘇珊，你可以報導第一個，戴夫第二個。

Okay. Thank you. So I think the opportunity for datopotamab deruxtecan is extensive in many different settings. So you will see a range of different trials that we'll be pursuing. Obviously, in PD-L1 high, pembrolizumab is an accepted standard of care. So I think the design of TROPION-Lung08, which is being run by colleagues at Daiichi Sankyo is logical in that regard. But we will be continuing to develop just this particular ADC in a number of different settings. So you can expect to see more on that later.

好的。謝謝你。所以我認為 datopotamab deruxtecan 的機會在許多不同的環境中是廣泛的。因此，您將看到我們將進行的一系列不同的試驗。顯然，在 PD-L1 高時，派姆單抗是公認的護理標準。所以我認為第一三共的同事正在運營的 TROPION-Lung08 的設計在這方面是合乎邏輯的。但我們將繼續在許多不同的環境中開發這個特定的 ADC。因此，您可以期待稍後看到更多信息。

In terms of the opportunity for Enhertu in the early stages of breast cancer, again, we're continuing to look at the development of this agent in many different settings. And again, you will continue to see further trials that will be announced as we're ready to in the coming months and years.

就 Enhertu 在乳腺癌早期階段的機會而言，我們正在繼續研究這種藥物在許多不同環境中的發展。同樣，您將繼續看到我們準備在未來幾個月和幾年內宣布的進一步試驗。

Sorry, can you just give us any perspective on TIGIT, clinical provisioning and [manifestation]?

抱歉，您能否就 TIGIT、臨床供應和 [表現] 給我們一些看法？

So again, I think there are different opportunities for these settings. I think they add different pieces to it. Obviously, I think -- I suppose, we want to do it to counter the different mechanism of action from an additional checkpoint inhibitor in that setting. So I think they're going to have -- as you see, the evolution of the next wave of immuno-oncology agents and the introduction of antibody-drug conjugates.

再說一次，我認為這些設置有不同的機會。我認為他們添加了不同的部分。顯然，我認為 - 我想，我們希望這樣做是為了對抗該環境中額外檢查點抑製劑的不同作用機制。所以我認為他們將擁有——正如你所看到的，下一波免疫腫瘤藥物的發展和抗體藥物偶聯物的引入。

I actually think there's going to be an opportunity for combinations and potentially further segmentation of the space. So I think there are different opportunities and different patients may be interested in those different opportunities depending on their particular tumor type and their setting and their underlying fitness.

實際上，我認為將有機會進行組合併可能進一步細分空間。所以我認為有不同的機會，不同的患者可能對這些不同的機會感興趣，這取決於他們特定的腫瘤類型、他們的環境和他們的潛在健康狀況。

So just very quickly, Emmanuel, on and Daiichi Sankyo, just for everybody's benefit. I mean -- so there are 2 things that folks can sometimes mix. There's an arbitration. There's a litigation. The arbitration, which is a private matter between DS and Seagen, is something we're not party to and so we just don't comment on. In terms of the litigation that's going on in Texas, we're working together with Daiichi Sankyo to vigorously defend against the Seagen patent. We consider that patent, which expires in 2024, to be invalid.

所以很快，Emmanuel，就和 Daiichi Sankyo，只是為了每個人的利益。我的意思是——所以人們有時可以混合兩件事。有仲裁。有訴訟。仲裁是 DS 和 Seagen 之間的私事，我們不是當事人，因此我們不予置評。就德克薩斯州正在進行的訴訟而言，我們正在與第一三共公司合作，大力捍衛 Seagen 專利。我們認為該專利於 2024 年到期，無效。

Thanks, Dave. Next question is Adam Karlsson.

謝謝，戴夫。下一個問題是亞當卡爾森。

Just the one, in terms of initial integration costs and subsequent cost synergies from the Alexion acquisition. Now that some time has passed, how do you see the dynamic between these 2 factors developing over time? And when do you expect cost synergies to begin to be realized in earnest? And will this be quite a gradual process or more a front-loaded gain.

就最初的整合成本和收購 Alexion 的後續成本協同效應而言，僅此而已。現在已經過去了一段時間，您如何看待這兩個因素之間的動態變化？您預計成本協同效應何時開始真正實現？這將是一個相當漸進的過程，還是更多的前置增益。

Marc?

馬克?

Yes. So we had announced $500 million synergy from the third year post closing. We are confirming these numbers. To your question, when do these synergies start appearing? I can just say that they will start appearing, to a limited extent, from 2021. But the full extent, the 100% of the synergies will be delivered in 2024. And obviously, this will progressively grow over time.

是的。因此，我們在交易結束後的第三年宣布了 5 億美元的協同效應。我們正在確認這些數字。對於您的問題，這些協同作用什麼時候開始出現？我只能說，它們將從 2021 年開始在一定程度上開始出現。但在整個範圍內，100% 的協同效應將在 2024 年實現。顯然，這將隨著時間的推移而逐漸增長。

Thanks, Marc. Next question is Seamus Fernandez.

謝謝，馬克。下一個問題是 Seamus Fernandez。

So I wanted to kind of come back to VBP. I think the comment was that we could see, I guess, what would potentially be a net reduction of about 50% for silicon. We've got the pressures from VBP this quarter. Really 2 elements to this question, trying to get a better understanding of the underlying operating profit contribution and -- from China going forward, and the incremental pressure points that we could see as potential generics. I think we have patent expirations at least listed coming in China in 2024 for Lynparza and potentially also relative to Farxiga.

所以我想回到VBP。我認為評論是我們可以看到，我猜，矽可能會淨減少約 50%。本季度我們受到了 VBP 的壓力。這個問題真的有兩個要素，試圖更好地了解潛在的營業利潤貢獻和 - 從中國向前發展，以及我們可以視為潛在仿製藥的增量壓力點。我認為我們至少在 2024 年在中國列出了 Lynparza 的專利到期，並且可能還與 Farxiga 相關。

So I was just hoping you could help us clarify some of those patent time lines and when we might see generics to those products. the operating profit contribution that you're anticipating from China, if you expect that to be meaningfully incremental going forward over the next 2 to 3 years? And then just as we think about VBP in China, is there a way to kind of help us characterize the year-over-year impact of VBP so there are a limited number of surprises in 2022?

所以我只是希望你能幫助我們澄清一些專利時間線，以及我們何時可以看到這些產品的仿製藥。如果您預計未來 2 到 3 年會顯著增加，您預計中國的營業利潤貢獻是多少？然後就像我們思考中國的 VBP 一樣，有沒有一種方法可以幫助我們描述 VBP 的同比影響，以便在 2022 年出現有限數量的意外？

So it's one question, but it's probably a 1-hour discussion. So if that's okay with you, we could follow up with you separately because there are so many pieces you've raised there. I'll make a general comment, which is over the next 4, 5 years, we still expect, on the CAGR basis -- on a CAGR basis, we still expect China to grow by high single digit. I mean China is definitely going to be under pressure. We've said it before. And China being china, it moves at light speed and things happen faster than anybody expected.

所以這是一個問題，但可能需要 1 小時的討論。所以如果你沒問題，我們可以單獨跟進你，因為你在那裡提出了很多作品。我將做一個一般性評論，在未來 4 到 5 年，我們仍然預計，在復合年增長率的基礎上——在復合年增長率的基礎上，我們仍然預計中國將以高個位數增長。我的意思是，中國肯定會承受壓力。我們以前說過。中國就是中國，它以光速前進，事情發生的速度比任何人預期的都要快。

But we still have a strong business. We are fast-tracking the approval of our new products. So we still believe it will be a reasonable business for us. But the growth rate will not be 20%, 30% like we've experienced in the last few years. I mean we are #1 in the market, and we, again, still expect to grow by high single digit on a CAGR basis. We'll give more color on '22 when we guide in January. But in terms of individual pieces you've raised, we could actually follow up with you. So we get -- give a chance to the last 3 or 4 questions Luisa Hector. Over to you, Luisa.

但我們仍然擁有強大的業務。我們正在快速跟踪我們的新產品的批准。所以我們仍然相信這對我們來說是一項合理的業務。但增長率不會像我們過去幾年所經歷的那樣是 20%、30%。我的意思是我們在市場上排名第一，我們仍然希望在復合年增長率的基礎上以高個位數增長。當我們在一月份指導時，我們將在 22 年提供更多顏色。但就您提出的個別作品而言，我們實際上可以跟進您。所以我們得到 - 給最後 3 或 4 個問題 Luisa Hector 的機會。交給你了，路易莎。

Pascal, on -- maybe a question for Dave. I mean it was a good quarter. Just checking on what was driving growth, any stocking benefits? Or is this very much the duration of use, perhaps some market share gains rather than COVID recovery, because your competitor still talks about the COVID impact? And for Mene or Ruud, the Saphnelo launch, just a little bit more color on the target patients reimbursement just so we can think about the pace of that sales ramp. And I noticed lupus nephritis Phase II did not meet the primary endpoints. So have you stopped development there?

帕斯卡，關於——也許是給戴夫的問題。我的意思是這是一個很好的季度。只是檢查是什麼推動了增長，任何庫存收益？或者這與使用時間很長，也許是一些市場份額的增加而不是 COVID 的恢復，因為您的競爭對手仍在談論 COVID 的影響？而對於 Mene 或 Ruud，Saphnelo 的推出，只是在目標患者報銷上增加了一點顏色，這樣我們就可以考慮銷售增長的速度。我注意到狼瘡腎炎 II 期沒有達到主要終點。那麼你有沒有停止那裡的開發？

So maybe Ruud, you could cover the Saphnelo question. The first one, I missed what product that is. So it may have been an oncology product for you, Dave, but I'm sorry, I missed it.

所以也許 Ruud，你可以討論一下 Saphnelo 的問題。第一個，我錯過了那是什麼產品。所以它可能對你來說是一種腫瘤學產品，戴夫，但我很抱歉，我錯過了。

Sorry, it was Calquence.

對不起，是卡爾昆斯。

Calquence, so over to you, Dave. And then the next one is Ruud, yes.

Calquence，交給你了，戴夫。然後下一個是路德，是的。

Sure. So Luisa, I mean I think as we highlighted and I highlighted, pretty pleased with the Calquence performance. The specifics on the question that you're asking, I mean, we're seeing good growth in new patient starts in CLL. We're seeing also that correspond with good growth in TRx-es. We see that the CLL uptake that's also taking place is happening in naive patients. And I think that's really important, obviously, in terms of getting that kind of frontline. When I say naive, I mean BTKI-naive patients.

當然。所以 Luisa，我的意思是，當我們強調和強調時，我對 Calquence 的表現非常滿意。關於你所問問題的具體細節，我的意思是，我們看到 CLL 新患者開始出現良好增長。我們也看到這與 TRx-es 的良好增長相對應。我們看到也發生在幼稚患者身上的 CLL 攝取。而且我認為這很重要，顯然，就獲得那種前線而言。當我說幼稚時，我指的是 BTKI 幼稚患者。

So this is a demand story that we're seeing right now. There's probably some kind of COVID elements that are in here. It's one where though there were some COVID benefits in switches from immunochemotherapy. This is one product where we saw some benefits to that. So I think that what I would say is that for us, this is a demand story and one that I'm proud of the work that the team's doing to really establish this brand is best-in-class.

所以這是我們現在看到的需求故事。這裡可能有某種 COVID 元素。儘管免疫化學療法的轉換對 COVID 有一些好處，但這是其中之一。這是我們看到一些好處的產品。所以我認為我想說的是，對我們來說，這是一個需求故事，我為團隊為真正建立這個品牌所做的工作感到自豪，這是一流的。

Ruud?

路德？

Okay. Let me quickly address the question about Saphnelo for lupus. Clearly, we see some very good early response from physicians. Equally, it's pleasing to see that we see patients, both in first line as well as in controls. Reimbursement is still, of course, a work in progress, although we're quite pleased where we are. And we're still very early in the launch. But there are also a couple of, clearly, challenges. We are still launching this product in COVID time.

好的。讓我快速解決關於狼瘡的 Saphnelo 的問題。顯然，我們看到了醫生的一些非常好的早期反應。同樣，很高興看到我們看到患者，無論是在一線還是在對照組。當然，報銷仍在進行中，儘管我們對目前的情況感到非常滿意。而且我們還處於發布的早期階段。但顯然也存在一些挑戰。我們仍在 COVID 時間推出該產品。

Rheumatologists specifically are very sensitive with respect to immunocompromised patients like elderly patients, so they want to have all their patients vaccinated with COVID. And equally, of course, we are still not having a permanent J-Code. But although the signals are looking good, and we have a very dedicated team in place. And clearly, 2022 will be the year where we will see hopefully, the fruits of our efforts here, Luisa.

風濕病學家對免疫功能低下的患者（如老年患者）特別敏感，因此他們希望所有患者都接種 COVID 疫苗。同樣，當然，我們仍然沒有永久的 J-Code。但是，儘管信號看起來不錯，而且我們有一個非常敬業的團隊。很明顯，2022 年將是我們希望看到我們在這裡努力成果的一年，路易莎。

There was a question on lupus nephritis, I don't know if I'm -- can you hear me?

有一個關於狼瘡性腎炎的問題，我不知道我是否——你能聽到我的聲音嗎？

Yes, we can hear you.

是的，我們可以聽到你的聲音。

Just on your question on lupus nephritis, so actually, although the study was -- didn't meet its primary endpoint, there were 2 dose regimens. One was the normal regimen. One was an intensified regimen actually the intensified regimen, Luisa, showed very encouragingly, I think, clinically meaningful benefits relative to the placebo arm. And so that is the regimen that we're taking forward right now into late-stage studies. And of course, this is another population or benefit from the lab, just to add to Ruud's comment around an immune-suppressed population that we're already going to be working with.

就您關於狼瘡性腎炎的問題而言，實際上，儘管該研究沒有達到其主要終點，但有 2 種劑量方案。一種是正常的治療方案。一種是強化方案，實際上強化方案 Luisa 顯示了非常令人鼓舞的，我認為，相對於安慰劑組具有臨床意義的益處。這就是我們現在正在推進到後期研究的方案。當然，這是另一個人群或從實驗室中受益，只是為了補充 Ruud 關於我們已經將要與之合作的免疫抑制人群的評論。

Next question is Victor [Sendai]. We're trying to -- actually, a bit, we're over time, but we want to cover your questions.

下一個問題是維克多[仙台]。我們正在嘗試——實際上，有點過了，但我們想解決您的問題。

So I have one of the rare disease portfolio. It seems like a lot of the growth case here is in neurology for your established portfolio. But given that myasthenia gravis is more of a common rare disease, I, guess versus PNH and aHUS, how much is the high price a challenge for you to expand in that indication, especially given that maybe the competitive pipeline with anti-FcRns will probably come in at a much lower price point if they get approved here going forward?

所以我有一個罕見的疾病組合。對於您已建立的投資組合，這裡的很多增長案例似乎都在神經病學領域。但鑑於重症肌無力更像是一種常見的罕見疾病，我猜與 PNH 和 aHUS 相比，高價對於您在該適應症中擴展的挑戰有多大，特別是考慮到可能具有抗 FcRns 的競爭性管道可能會如果他們在這裡獲得批准，以更低的價格進入？

Shall I take the question, Pascal?

我要回答這個問題嗎，帕斯卡？

Yes. Over to you, Marc.

是的。交給你了，馬克。

So for the time being, only Soliris is approved in the 2 neurology indications. Myasthenia gravis is one of them, neuromyelitis optica is the second one. The growth in terms of patients have been very substantial. You don't see the sales on Soliris grow because we are converting Soliris to Ultomiris in the legacy indication, PNH and atypical HUS. So you have these 2 opposite factors taking place.

所以目前，只有 Soliris 被批准用於 2 種神經學適應症。重症肌無力是其中之一，視神經脊髓炎是第二個。患者的增長非常可觀。您看不到 Soliris 的銷售額增長，因為我們正在將 Soliris 轉換為舊適應症、PNH 和非典型 HUS 中的 Ultomiris。所以你有這兩個相反的因素發生。

But the growth in neurology is very strong. Most of the utilization of Soliris in myasthenia gravis is for refractory patients, for patients for which any other treatment doesn't work.

但神經病學的增長非常強勁。 Soliris 在重症肌無力中的大部分應用是針對難治性患者，針對任何其他治療無效的患者。

We have recently opened a real study, a Phase III study for Ultomiris. This study is going to be fine with authorities, and we expect an approval in the course of 2022. So we will be converting Soliris patients to Ultomiris from 2022. And the label of Ultomiris hopefully will be wider than the label of Soliris. And -- but there will be also, as you mentioned, all the companies entering with all the mechanism in the field of myasthenia gravis but the field of myasthenia gravis is composed of very different segments. And I think Soliris and Ultomiris will keep retaining a strong advantage in this indication.

我們最近開展了一項真正的研究，一項針對 Ultomiris 的 III 期研究。這項研究會得到當局的認可，我們預計將在 2022 年獲得批准。因此，我們將從 2022 年開始將 Soliris 患者轉換為 Ultomiris。Ultomiris 的標籤有望比 Soliris 的標籤更廣泛。而且 - 但正如你所提到的，所有公司都會以所有機制進入重症肌無力領域，但重症肌無力領域由非常不同的部分組成。而且我認為 Soliris 和 Ultomiris 將在這一跡像中保持強大的優勢。

Thanks, Marc. So we'll take 2 last questions, and then we'll have to close. So we respect your time. So Christopher, I'd say, Christopher Uhde, you're on go.

謝謝，馬克。所以我們將回答最後兩個問題，然後我們將不得不結束。所以我們尊重你的時間。所以克里斯托弗，我會說，克里斯托弗·烏德，你要走了。

On PARP, the selective PARP, does Merck have an option for the selective PARP or indeed any other potential PARPs going forward? And just can you -- when it comes to -- I mean the choice of Zytiga versus XTANDI, can you remind us why you chose Zytiga for PROpel? And what are the future plans in prostate cancer moving earlier, for example? If you risk losing out to Pfizer as nonhormone therapy -- novel hormone therapies move up the treatment algorithm?

關於 PARP，選擇性 PARP，默克公司是否有選擇性 PARP 或任何其他潛在 PARP 的選項？你能不能——說到——我的意思是選擇 Zytiga 與 XTANDI，你能提醒我們為什麼選擇 Zytiga 作為 PROpel 嗎？例如，前列腺癌的未來計劃是什麼？如果您冒著輸給輝瑞（Pfizer）作為非激素療法的風險——新型激素療法會提升治療算法？

So I mean we typically do not comment on our current track. So maybe this one we'll -- Dave, do you want to cover the second question about prostate?

所以我的意思是我們通常不會評論我們當前的曲目。所以也許這個我們會 - 戴夫，你想談談關於前列腺的第二個問題嗎？

Yes, sure. I certainly invite Susan to offer any comment on this. I mean I think that in terms of this, there's a good and growing use of abiraterone that we see across the globe. And it's -- therefore, was a very logical NHA to include within this. Now obviously, there are other utilizations that are non-abi that exists. But that's the primary reason that was in there just in terms of the choice. Susan, do you want to add?

是的，當然。我當然邀請蘇珊對此發表任何評論。我的意思是，我認為就這一點而言，我們在全球範圍內看到阿比特龍的良好且不斷增長的使用。因此，將其包含在其中是一個非常合乎邏輯的 NHA。現在顯然，還有其他非 abi 用途存在。但這就是選擇的主要原因。蘇珊，你要補充嗎？

No, I think you've covered it.

不，我想你已經涵蓋了它。

So the last question, Andrew Berens of Leerink.

最後一個問題，Leerink 的 Andrew Berens。

Just a follow-up question on the Seagen and Daiichi arbitration. I know you said you're not involved in the contract dispute. But if it does result in a royalty paid to Seagen because they're found -- they're in a portion of the molecule, would that incremental cost impact your share of the profit? And then I also just wanted to get a clarification from Dave on his sizing in the adjuvant setting. He said, I think it was about 25% of the metastatic setting. But I thought that over 3 quarters of patients diagnosed with lung cancer and developed countries are amenable to surgery. So any color on the step off there?

只是關於 Seagen 和 Daiichi 仲裁的後續問題。我知道你說過你沒有捲入合同糾紛。但是，如果它確實導致向 Seagen 支付特許權使用費，因為它們被發現——它們在分子的一部分中，那麼增加的成本會影響你的利潤份額嗎？然後我也只是想從戴夫那裡得到一個關於他在輔助環境中的尺寸的澄清。他說，我認為這大約是轉移性環境的 25%。但我認為，超過四分之三的被診斷患有肺癌和發達國家的患者可以接受手術。那麼那裡的台階上有顏色嗎？

Dave?

戴夫？

Sure. So I mean I guess on the first piece, we don't really have anything more to add other than the comments that I offered on that we're just not -- we're not a party to the arbitration on that. So I think that's where we'll stay with right now.

當然。所以我的意思是，我想在第一部分中，除了我提供的評論之外，我們真的沒有什麼要補充的了——我們不是仲裁的一方。所以我認為這就是我們現在要堅持的地方。

On the adjuvant portion, we've been pretty, I think, consistent in talking about the fact that there's far too many patients in lung cancer that are diagnosed late. And in fact, I think it's also important to remember that we're talking about patients that are 1B to 3A. And so you've got, I don't know, about 60%, 65% of patients diagnosed in Stage 4. The balance of those are going to be 1A through your 3B -- yes, your 3B population. So the ADAURA indication itself is about 20% to 25% of the size of the FLAURA indication.

在輔助部分，我認為，我們一直在談論有太多肺癌患者被延遲診斷的事實。事實上，我認為記住我們談論的是 1B 到 3A 的患者也很重要。所以你有，我不知道，大約 60%，65% 的患者在第 4 階段被診斷出來。其餘的將是 1A 到 3B——是的，你的 3B 人群。所以 ADAURA 指示本身大約是 FLAURA 指示大小的 20% 到 25%。

And I think that really, the data are so impressive that we are really enthusiastic to be educating the multidisciplinary teams on utilization of these data. But adjuvant treatment is not something that is happening widely across the globe, and it's taking us some work and some effort to really make sure that it's happening. But we're pleased with the progress that we're making, and I'm confident that we will make good inroads in time into this important segment where we can really hopefully bend survival curves in this early stage.

而且我認為，這些數據確實令人印象深刻，以至於我們非常熱衷於教育多學科團隊使用這些數據。但是輔助治療並不是在全球範圍內廣泛發生的事情，我們需要一些工作和努力才能真正確保它正在發生。但我們對我們正在取得的進展感到高興，我相信我們將及時進入這個重要的領域，我們真的有希望在這個早期階段彎曲生存曲線。

Thank you, Dave. I mean, let me just very quickly close. And what I want to say is we continue to deliver a very strong growth. We've talked about China slowing down. And of course, we all know it's a more difficult environment. But other parts of the business are picking up speed. Overall, we still see pretty strong growth over this year and over the next few years. We are still in line with the growth rate we have communicated in the past on a CAGR basis to 2025. And where the pipeline is looking very strong, there's more to come, more growth to come. So we continue funding, of course, this pipeline.

謝謝你，戴夫。我的意思是，讓我很快關閉。我想說的是，我們繼續實現非常強勁的增長。我們已經談到中國正在放緩。當然，我們都知道這是一個更加困難的環境。但該業務的其他部分正在加快速度。總體而言，我們仍然看到今年和未來幾年的強勁增長。我們仍然與我們過去傳達的到 2025 年的複合年增長率保持一致。在管道看起來非常強勁的地方，還有更多的增長，更多的增長即將到來。因此，我們當然會繼續為這條管道提供資金。

Now between Q3 and Q4 this year, I mean, we have definitely calendarization questions. But there's no doubt in our mind that we will deliver on our guidance. We're very, very optimistic about it. And then if you look at it in the quarter, some people were asking, I mean, we will continue getting sales momentum there with a full quarter of Alexion on top because in Q3, we didn't have a full quarter there. I think Emmanuel and Matt -- or Matt was asking questions about the collaboration revenue, the milestone. I would just guide you to the consensus in terms of what you have there.

現在在今年第三季度和第四季度之間，我的意思是，我們肯定有日曆問題。但毫無疑問，我們將兌現我們的指導。我們對此非常非常樂觀。然後，如果您在本季度查看它，有些人會問，我的意思是，我們將繼續在那裡獲得銷售勢頭，其中 Alexion 的整整一個季度在頂部，因為在第三季度，我們在那裡沒有一個完整的季度。我認為伊曼紐爾和馬特——或者馬特在問關於合作收入、里程碑的問題。我只是引導你就你所擁有的達成共識。

Expenses, we've talked about. I mean so if you take all of this into account, you can see that we expect to deliver our guidance for the year, and there's absolutely no concern in our mind. The COVID assets are delivering no profit overall. But the good news is we're moving now progressively into a profitable mode for the vaccine. It will be always a modest profitability, but it will be profitable.

費用，我們已經談過了。我的意思是，如果您將所有這些考慮在內，您會看到我們希望提供今年的指導，而且我們絕對不會擔心。 COVID 資產總體上沒有帶來任何利潤。但好消息是，我們現在正逐步進入疫苗的盈利模式。這將永遠是一個適度的盈利能力，但它會是有利可圖的。

And the lab, in particular, we believe, has a substantial place in prophylaxis for patients who have immune issues like transplant patients, cancer patients, patients with immunosuppressive therapy, et cetera. So we see quite a big potential for this one.

我們認為，特別是該實驗室在預防有免疫問題的患者（如移植患者、癌症患者、免疫抑制治療患者等）方面具有重要地位。所以我們看到了這個巨大的潛力。

So net-net is, we still see ourselves as a very -- as a company growing very strongly over the next few years. And of course, we will continue improving our operating margin, as we've said. No change to what we've told you in the past. So again, thank you so much for your interest in our company, and we look forward to more good news over the next few quarters. Thank you.

所以 net-net 是，我們仍然認為自己是一家非常 - 作為一家在未來幾年內增長非常強勁的公司。當然，正如我們所說，我們將繼續提高我們的營業利潤率。與我們過去告訴您的內容沒有任何變化。再次感謝您對我們公司的關注，我們期待在接下來的幾個季度裡有更多的好消息。謝謝你。