AstraZeneca PLC (AZN) 2020 Q4 法說會逐字稿

Good morning to those joining from the U.K. and the U.S. Good afternoon to those in Central Europe. Welcome, ladies and gentlemen, to AstraZeneca's Full Year 2020 Results Conference Call and Webcast for Investors and Analysts.

早上好，來自英國和美國的參會者。下午好，中歐的參會者。女士們，先生們，歡迎參加阿斯利康 2020 年全年業績電話會議和麵向投資者和分析師的網絡廣播。

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

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

(Operator Instructions)

（操作員說明）

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

那麼，我現在將把你交給公司。

Hello, everyone. It's Pascal Soriot, CEO of AstraZeneca. Welcome to the full year 2020 conference call and our webcast for investors and analysts.

大家好。我是阿斯利康公司的首席執行官 Pascal Soriot。歡迎參加 2020 年全年電話會議和我們面向投資者和分析師的網絡直播。

As usual, the presentation was posted to astrazeneca.com, and we have also sent it to people on our distribution list. Please turn to Slide 2. These are the usual safe harbor statements, including an Alexion-related [bonus].

像往常一樣，該演示文稿已發佈到 astrazeneca.com，我們也已將其發送給我們通訊組列表中的人員。請轉到幻燈片 2。這些是通常的安全港聲明，包括與 Alexion 相關的[獎金]。

On Slide 3. We will be making comments on our performance using constant exchange rates or CER, core financial numbers and non-GAAP measures. A reconciliation between non-GAAP and GAAP data is contained in the results announcement. All numbers are in million U.S. dollars and refer to full year 2020 unless we state otherwise. And finally, compared to past quarters, we need to be a little bit more hamstrung with financial guidance this time due to the ongoing work with election -- Alexion. Thank you for your understanding here, as we are limited in our potential comments, in particular on 2021.

在幻燈片 3 上。我們將使用固定匯率或 CER、核心財務數據和非 GAAP 指標對我們的業績發表評論。非 GAAP 和 GAAP 數據之間的對賬包含在業績公告中。除非另有說明，否則所有數字均以百萬美元為單位，指的是 2020 年全年。最後，與過去幾個季度相比，由於正在進行的選舉工作 -- Alexion，我們這次需要在財務指導方面更加受阻。在此感謝您的理解，因為我們的潛在評論有限，尤其是在 2021 年。

Please turn to Slide 4. We plan to review the presentation first and then do a Q&A until 1:15 U.K. time. If you keep questions short, we will try to keep answers short too. (Operator Instructions) There's also an option to ask questions as part of the webcast. (Operator Instructions) Thanks for your help on this one.

請轉到幻燈片 4。我們計劃先回顧演示文稿，然後在英國時間 1:15 之前進行問答。如果您的問題簡短，我們也會盡量簡短回答。 （操作員說明）作為網絡廣播的一部分，還可以選擇提問。 （操作員說明）感謝您對此的幫助。

In speaking order: I'm joined by Dave Fredrickson, who is our EVP of the Oncology business unit; Ruud Dobber, the EVP of the BioPharmaceuticals business unit; Marc Dunoyer, our CFO; Mene Pangalos, our EVP of the biopharmaceutical [R&DU]; and then again Dave, to cover for José Baselga today on Oncology R&D before handing back. For the questions later, we also have Pam Cheng, EVP for operations and also IT. And we also have Leon Wang, who is the EVP responsible for China and the emerging markets. We also have online with us Susan Galbraith, who many of you know; and Cristian Massacesi, who -- our Board Senior Vice President in Oncology R&D; Susan for the early part. And Cristian is in charge of the late-stage pipeline in Oncology R&D. We plan to first take questions on the ongoing business, and then we save any questions on the vaccine for the last part of the conference call and the webcast. We hope that works for everyone.

按發言順序：戴夫·弗雷德里克森 (Dave Fredrickson) 加入了我的行列，他是我們腫瘤業務部門的執行副總裁；生物製藥業務部執行副總裁 Ruud Dobber；我們的首席財務官 Marc Dunoyer； Mene Pangalos，我們的生物製藥 [R&DU] 執行副總裁；然後是 Dave，在返回之前為 José Baselga 報導腫瘤學研發。對於稍後的問題，我們還有運營和 IT 執行副總裁 Pam Cheng。我們還有 Leon Wang，他是負責中國和新興市場的執行副總裁。我們還有在線採訪 Susan Galbraith，你們很多人都認識她；和 Cristian Massacesi，他是我們董事會腫瘤研發高級副總裁；蘇珊的早期部分。 Cristian 負責腫瘤學研發的後期管線。我們計劃首先回答有關正在進行的業務的問題，然後我們將有關疫苗的任何問題留到電話會議和網絡廣播的最後部分。我們希望這對每個人都有效。

Please turn to Slide 5. This is the agenda, where we plan to cover all key aspects of our results today.

請轉到幻燈片 5。這是議程，我們計劃在其中涵蓋今天結果的所有關鍵方面。

Moving on to Slide 6.

轉到幻燈片 6。

In 2020, performance was strong and resilient, and we delivered the guidance as promised. The 10% increase in revenue was underpinned by the focused R&D and our SG&A investment and despite the headwinds from the pandemic in many parts of the global business. New medicines were up 33%, and we saw continued performance from Oncology and New CVRM. Respiratory & Immunology was stable, but it improved a lot in the last quarter. And the Emerging Markets were up by 10%, with growth impacted by COVID-19 on Pulmicort.

2020 年，業績強勁且富有彈性，我們如期交付了指導意見。收入增長 10% 的基礎是專注的研發和我們的 SG&A 投資，儘管全球業務的許多地方都受到大流行的不利影響。新藥增長了 33%，我們看到腫瘤學和新 CVRM 的持續表現。呼吸與免疫學穩定，但在最後一個季度有很大改善。新興市場增長了 10%，增長受到 COVID-19 對 Pulmicort 的影響。

Core operating profit grew by 17% despite 2% lower core operating income. With a tax rate of 20%, core EPS ended at $4.02, up by 18%, and more than revenue, delivering operating leverage. As a result, guidance was achieved as we promised for the year. Our cash flow improved, including net cash inflow from operating activities now $4.8 billion, supporting the progressive dividend policy.

儘管核心營業收入下降了 2%，但核心營業利潤增長了 17%。在稅率為 20% 的情況下，核心 EPS 收於 4.02 美元，增長 18%，超過收入，提供運營槓桿。結果，實現了我們當年承諾的指導。我們的現金流有所改善，包括來自經營活動的淨現金流入現在為 48 億美元，支持漸進式股息政策。

We continues to see strong progress in the pipeline, mostly on approvals, supporting sales today and, of course, tomorrow. This year, we are back with more Phase III trial readouts like Calquence recently.

我們繼續看到管道中的強勁進展，主要是在批准方面，支持今天和明天的銷售。今年，我們回來了更多的 III 期試驗讀數，比如最近的 Calquence。

The efforts against the COVID-19 pandemic continued with the first authorization for the vaccine. Let me assure everyone today that we are doing our very best to deliver it to governments as promised. During this first half, we anticipate Phase III data for the long-acting antibody combination, the potential new medicine AZD7442. Our production of the vaccine is very substantial, and in the month of February, we expect to manufacture 100 million doses globally across our supply chain consortium and 200 million doses per month starting in April.

隨著疫苗的首次授權，抗擊 COVID-19 大流行的努力繼續進行。今天讓我向大家保證，我們正在盡最大努力按照承諾將其交付給各國政府。在上半年，我們預計長效抗體組合的 III 期數據，即潛在的新藥 AZD7442。我們的疫苗產量非常大，在 2 月份，我們預計我們的供應鏈聯盟將在全球範圍內生產 1 億劑疫苗，並從 4 月份開始每月生產 2 億劑疫苗。

In 2021, we anticipate another year of double-digit revenue growth in the low teens, with that revenue growth accompanied by even faster growth in core EPS to between $4.75 and $5, all of these at constant exchange rates. Marc will provide more details later.

到 2021 年，我們預計青少年收入將再次實現兩位數增長，收入增長伴隨著核心每股收益更快增長，達到 4.75 美元至 5 美元之間，所有這些均按固定匯率計算。馬克稍後會提供更多細節。

Please turn to Slide 7. If we look at the pipeline news flow since the results announcement in November, a few highlights: There were a few -- a high number of approvals for the key cancer medicines across users and geographies. We made regulatory submissions for a number of new uses of our leading medicines in all therapy areas and we've obtained several priority reviews as well. Our clinical trial readouts also picked up, and we anticipate more of this as we move further into 2021. We will detail this news flow a little later. All in all, an increase in activity levels and more progress to the future benefit of patients. We're not slowing down. If anything, we are actually speeding up.

請轉到幻燈片 7。如果我們看一下自 11 月結果公佈以來的管道新聞流，有一些亮點：有一些 - 跨用戶和地區的關鍵癌症藥物獲得了大量批准。我們就我們領先藥物在所有治療領域的一些新用途提交了監管申請，我們也獲得了多項優先審查。我們的臨床試驗讀數也有所回升，隨著我們進一步進入 2021 年，我們預計會有更多這樣的數據。稍後我們將詳細介紹這一新聞流。總而言之，活動水平的提高和對患者未來益處的更多進展。我們並沒有放慢腳步。如果有的話，我們實際上正在加速。

Please turn to Slide 8. After the financial headlines and our pipeline, we now take a deeper dive into revenue. Total revenue advanced by 10% in the last quarter, with growth benefiting from the Lynparza sales milestone that we have discussed at the last conference call. Looking only at product sales, the growth was 11%.

請轉到幻燈片 8。在財務頭條和我們的管道之後，我們現在更深入地研究收入。上個季度總收入增長了 10%，增長得益於我們在上次電話會議上討論的 Lynparza 銷售里程碑。僅看產品銷售額，增長率為 11%。

There was some negative impact from COVID-19 on some of our new medicines, in particular Brilinta and some on Imfinzi and Fasenra. Despite this, new medicines added $3.5 billion of additional revenue, with Tagrisso, Imfinzi, Farxiga, Lynparza, Calquence and Fasenra as the biggest contributor. This is the strength of our company, the broad geographical coverage and the broad pipeline we have powered by several products. And of course, if 1 or 2 are impacted by COVID, some others can do well. And overall, you can see the progress is very strong. We now have 8 blockbuster medicines overall, and 13 new medicines contributing growth and adding further diversification to revenue as we look ahead.

COVID-19 對我們的一些新藥產生了一些負面影響，特別是 Brilinta 以及 Imfinzi 和 Fasenra 的一些新藥。儘管如此，新藥還是增加了 35 億美元的額外收入，其中 Tagrisso、Imfinzi、Farxiga、Lynparza、Calquence 和 Fasenra 是最大的貢獻者。這是我們公司的實力、廣泛的地理覆蓋範圍以及我們由多種產品提供支持的廣泛管道。當然，如果 1 或 2 人受到 COVID 的影響，其他一些人可以做得很好。總的來說，你可以看到進步非常大。展望未來，我們現在總共有 8 種重磅炸彈藥物和 13 種新藥有助於增長並進一步增加收入多元化。

So if we turn to Slide 9, aggregating medicines into therapy areas. We had solid double-digit growth for Oncology and high single-digit growth for New CVRM, with Respiratory & Immunology stable and improving in the last quarter despite the COVID-19 impact on Pulmicort. Excluding Pulmicort, there was 12% growth in Respiratory & Immunology in the year. If we look at things from a regional viewpoint, there was growth everywhere, with Europe improving growth markedly and the Emerging Markets continuing to grow, with the U.S. back as the largest region now.

因此，如果我們轉到幻燈片 9，將藥物匯總到治療領域。儘管 COVID-19 對 Pulmicort 產生了影響，但我們在腫瘤學方面實現了穩健的兩位數增長，在新 CVRM 方面實現了高個位數增長，呼吸和免疫學在上個季度保持穩定並有所改善。不包括 Pulmicort，呼吸與免疫學在這一年增長了 12%。如果我們從區域的角度來看，到處都有增長，歐洲增長顯著改善，新興市場繼續增長，美國現在重新成為最大的地區。

In summary. The results for 2020 confirm the strategic direction of our company and our confidence in our business and the future of sustainable and durable growth across [many scenes] and across geographical markets. With a global revenue base and the diversified portfolio of new medicines and with more to come, AstraZeneca remains well positioned in the current pandemic environment. We want to remain agile and ready to act entrepreneurially when opportunities arise, as evidenced in our efforts against COVID-19 as well as the proposed acquisition of Alexion.

總之。 2020 年的業績證實了我們公司的戰略方向以及我們對業務的信心以及跨 [許多場景] 和跨地域市場的可持續和持久增長的未來。憑藉全球收入基礎和多元化的新藥組合以及更多新藥，阿斯利康在當前的大流行環境中仍然處於有利地位。我們希望保持敏捷，並準備好在機會出現時採取企業家精神，這在我們針對 COVID-19 的努力以及對 Alexion 的擬議收購中得到了證明。

So please turn to Slide 10. On Alexion, we have made good progress ahead of the anticipated closing in the third quarter. Alexion continues to offer a compelling scientific and business complementarity and will allow us to build out in immunology long term, helping Alexion build better rare medicines using some of our platforms and help us expand into new and broader indications in immunology. So a very strong scientific complementarity that will strengthen the portfolio of our existing business but also the portfolio of Alexion. In the short and medium term, the combined company will offer also faster growth, improved profitability and cash flow; and that will sustain the positive project developments achieved since 2013.

所以請轉到幻燈片 10。在 Alexion 方面，我們在預期的第三季度結束之前取得了良好的進展。 Alexion 繼續提供令人信服的科學和業務互補性，將使我們能夠在免疫學領域長期發展，幫助 Alexion 使用我們的一些平台開發更好的稀有藥物，並幫助我們擴展到新的和更廣泛的免疫學適應症。因此，非常強大的科學互補性將加強我們現有業務的組合，也將加強 Alexion 的組合。從短期和中期來看，合併後的公司還將提供更快的增長、更高的盈利能力和現金流；這將維持自 2013 年以來取得的積極項目發展。

Before closing, I would like to say how grateful I am for the support and hard work from our more than 70,000 colleagues in AstraZeneca and all the potential new colleagues in Alexion. And I would like to thank everyone for their efforts in the current situation fighting the virus but always putting patients and their unmet medical needs first across all our business areas and geographical regions.

在結束之前，我想對阿斯利康 70,000 多名同事以及 Alexion 所有潛在的新同事的支持和辛勤工作表示感謝。我要感謝大家在當前形勢下與病毒作鬥爭的努力，但始終將患者及其未滿足的醫療需求放在我們所有業務領域和地理區域的首位。

I will now hand over to Dave, who will go into details of our Oncology business. Please go ahead, Dave. And please turn to Slide 11.

我現在將交給戴夫，他將詳細介紹我們的腫瘤業務。請繼續，戴夫。請轉到幻燈片 11。

Thank you, Pascal.

謝謝你，帕斯卡。

We're pleased to report a strong growth in total revenue of 24% for the Oncology business to $11.5 billion in the year. COVID did continue to have impact, with fewer cancer patients diagnosed and treated, but we saw resilience in our business as sales grew across all of our new oncology medicines from regional expansions and new launches.

我們很高興地報告，今年腫瘤業務總收入強勁增長 24%，達到 115 億美元。 COVID 確實繼續產生影響，診斷和治療的癌症患者減少了，但隨著區域擴張和新推出的所有新腫瘤藥物的銷售額增長，我們看到了業務的彈性。

Please turn to Slide 12. Starting with our lung cancer franchise, we're pleased to report that both Tagrisso and Imfinzi showed strong growth in the year at 36% and 39%, respectively, with revenue of $4.3 billion and $2 billion.

請轉到幻燈片 12。從我們的肺癌專營權開始，我們很高興地報告 Tagrisso 和 Imfinzi 在這一年中分別實現了 36% 和 39% 的強勁增長，收入分別為 43 億美元和 20 億美元。

Tagrisso continues its global rollout and is now approved in 87 countries in the first-line setting, and we saw continued expansion in countries with national reimbursement, which now totals 40. U.S. Tagrisso revenue was up 24%, where we saw continued single-digit demand growth. And we are now focused on bringing Tagrisso to patients with the earlier-stage lung cancer setting in the U.S. following the approval based upon the ADAURA Phase III trial as we await regulatory decisions outside of the U.S. In China, we were pleased to be able to successfully negotiate reimbursement to enable even more patients to access Tagrisso as a first-line treatment in the metastatic setting.

Tagrisso 繼續在全球推出，目前已在 87 個國家/地區獲得一線批准，我們看到國家報銷的國家繼續擴大，目前總數為 40 個。美國 Tagrisso 收入增長了 24%，我們看到繼續保持個位數需求增長。在根據 ADAURA III 期試驗獲得批准後，我們現在專注於將 Tagrisso 帶給美國早期肺癌患者，因為我們正在等待美國以外的監管決定。在中國，我們很高興能夠成功協商報銷，使更多患者能夠將 Tagrisso 作為轉移性治療的一線治療藥物。

The majority of Imfinzi revenue continued to come from the United States as the launch of the CASPIAN indication in extensive-stage small cell lung cancer continued to take effect, although we did see impacts here from COVID on patient diagnoses. Outside of the U.S., we continue to see revenue of Imfinzi pick up, particularly in Europe and Emerging Markets as we are now able to provide Imfinzi to a -- more small cell cancer patients globally. The unique ability to combine with both cisplatin and carboplatin chemotherapy will further benefit patients.

Imfinzi 的大部分收入繼續來自美國，因為在廣泛期小細胞肺癌中推出 CASPIAN 適應症繼續生效，儘管我們確實看到了 COVID 對患者診斷的影響。在美國以外，我們繼續看到 Imfinzi 的收入回升，特別是在歐洲和新興市場，因為我們現在能夠為全球更多的小細胞癌患者提供 Imfinzi 。與順鉑和卡鉑化療聯合使用的獨特能力將進一步造福患者。

Please turn to Slide 13. Lynparza continued to demonstrate progress with sales up by 49%, with just over half of sales coming from outside of the United States. This is a result of growth across all regions as more breast and ovarian cancer patients gained access to Lynparza in the major regions of the U.S., in Europe and in Japan. U.S. sales continued to grow by 40%, with increased demand as Lynparza maintained its leadership in the PARP market in both ovarian and prostate cancer as we launched the PAOLA-1 indication in first-line HRD-positive ovarian cancer and the profound prostate cancer indication.

請轉到幻燈片 13。 Lynparza 繼續展示進展，銷售額增長了 49%，其中超過一半的銷售額來自美國以外。這是所有地區增長的結果，因為越來越多的乳腺癌和卵巢癌患者在美國、歐洲和日本的主要地區獲得了 Lynparza。隨著我們在一線 HRD 陽性卵巢癌和深度前列腺癌適應症中推出 PAOLA-1 適應症，Lynparza 在卵巢癌和前列腺癌 PARP 市場保持領先地位，美國銷售額繼續增長 40%，需求增加.

Europe sales were up by 51%, as more first-line ovarian cancer patients received Lynparza as we now look forward to the ovarian PAOLA-1 and prostate launches in Europe following the recent approvals towards the end of last year. Emerging Markets sales grew by 108%, driven by the China launch and the recent inclusion on the NRDL. This should be further aided by an additional successful reimbursement decision awarded this year. Japan sales amounted to $167 million, with growth of 27% driven by uptake in ovarian and breast cancers.

歐洲銷售額增長了 51%，因為更多的一線卵巢癌患者接受了 Lynparza，因為我們現在期待卵巢 PAOLA-1 和前列腺在去年底最近獲得批准後在歐洲上市。新興市場的銷售額增長了 108%，這得益於中國的推出和最近被納入 NRDL。這應該得到今年額外成功的報銷決定的幫助。日本的銷售額達到 1.67 億美元，增長了 27%，這主要得益於卵巢癌和乳腺癌的治療。

Please turn to Slide 14, turning now to the newer launches, Calquence in chronic lymphocytic leukemia and Enhertu in third-line HER2-positive metastatic breast cancer. I'm pleased to report the Calquence revenue of $522 million in the year almost exclusively in the United States, as the 2019 CLL launch really took effect. The launch feedback continues to be very encouraging as the very impressive Phase III data are resonating well with physicians, including the recently announced head-to-head data versus the incumbent BTK inhibitor, reinforcing our belief in Calquence as a potential best-in-class medicine. We are encouraged to see that Calquence is now 1/3 share of front-line CLL new patient starts in the BTK inhibitor class in the U.S. We look forward to bringing Calquence to CLL patients in Europe and Japan following the recent approvals at the beginning of 2021.

請轉到幻燈片 14，現在轉到更新的產品，慢性淋巴細胞白血病的 Calquence 和三線 HER2 陽性轉移性乳腺癌的 Enhertu。我很高興地報告 Calquence 在這一年的收入為 5.22 億美元，幾乎完全來自美國，因為 2019 年 CLL 的推出確實生效了。發布反饋仍然非常令人鼓舞，因為非常令人印象深刻的 III 期數據與醫生產生了良好的共鳴，包括最近公佈的與現有 BTK 抑製劑的頭對頭數據，加強了我們對 Calquence 作為潛在同類最佳藥物的信念藥品。我們很高興看到 Calquence 現在占美國 BTK 抑製劑類一線 CLL 新患者開始治療的 1/3 2021.

Following the Enhertu launch at the beginning of the year, we're pleased to have reported $96 million in collaboration revenue based on $200 million of U.S. sales booked by Daiichi Sankyo in the year. Enhertu is the most prescribed medicine in the third-line setting of HER2-positive metastatic breast cancer.

在今年年初推出 Enhertu 之後，我們很高興地報告了 9600 萬美元的合作收入，基於 Daiichi Sankyo 當年在美國的 2 億美元銷售額。 Enhertu 是 HER2 陽性轉移性乳腺癌三線治療中處方最多的藥物。

I'll now turn over to Ruud for an update on our BioPharmaceuticals business and Emerging Markets. Please turn to Slide 15.

我現在將轉交給 Ruud，了解我們的生物製藥業務和新興市場的最新情況。請轉到幻燈片 15。

Many thanks, Dave.

非常感謝，戴夫。

Today, I'm pleased to talk to you about the BioPharmaceuticals business. Total revenue of biopharma, comprising New Cardiovascular, Renal and Metabolism and Respiratory & Immunology, was $10 billion in the year, growing at 4% despite the COVID dynamic.

今天，我很高興與您談論生物製藥業務。包括新心血管、腎臟和新陳代謝以及呼吸和免疫學在內的生物製藥的總收入在這一年為 100 億美元，儘管 COVID 充滿活力，但仍以 4% 的速度增長。

Starting with New CVRM. Revenue was up by 9%, with total revenue at $4.7 billion, with very strong growth from Farxiga.

從新 CVRM 開始。收入增長了 9%，總收入為 47 億美元，來自 Farxiga 的增長非常強勁。

Farxiga maintained volume market share globally, with high double-digit volume growth across all regions, as the fastest-growing SGLT2 inhibitor. In the United States, Farxiga grew 6%, driven by the additional indication in heart failure. Outside the U.S., which accounted for 71% of revenue, we saw strong performances with volume-driven growth increasing and China benefiting from the NRDL listing.

作為增長最快的 SGLT2 抑製劑，Farxiga 保持了全球銷量市場份額，在所有地區均實現了兩位數的高銷量增長。在美國，Farxiga 增長了 6%，這得益於心力衰竭的額外適應症。在佔收入 71% 的美國之外，我們看到了強勁的表現，銷量驅動的增長不斷增加，中國受益於 NRDL 的上市。

Brilinta delivered revenue of $1.6 billion, with 2% growth, as the impact from COVID resulted in fewer hospital patients and China experienced the impact on VBP-driven price reductions. Sales in the U.S. were up by 3%, as an increase in treatments duration offset the negative COVID-19 impacts. The majority of use is still in the acute setting, and Brilinta continues to outgrow the market in the majority of regions.

Brilinta 實現了 16 億美元的收入，增長了 2%，這是因為 COVID 的影響導致住院患者減少，而中國經歷了 VBP 驅動的降價的影響。由於治療時間的延長抵消了 COVID-19 的負面影響，美國的銷售額增長了 3%。大多數使用仍處於急性環境中，而 Brilinta 在大多數地區的增長繼續超過市場。

Please turn to Slide 16, turning to Respiratory & Immunology. We reported revenue of $5.4 billion, stable in the year, but excluding Pulmicort, Respiratory & Immunology grew 12%.

請轉到幻燈片 16，轉到呼吸與免疫學。我們報告的收入為 54 億美元，全年穩定，但不包括 Pulmicort，呼吸與免疫學增長了 12%。

Symbicort's sales were strong at $2.7 billion, with a growth of 10% in the year. The U.S. saw particularly strong growth, up 23% to $1 billion due to demand growth following the launch of the orphan generic and a resilient ICS/LABA market. Globally, Symbicort remained the leader in value and volume market share in the ICS/LABA class. Pulmicort was down 32% in the year with revenue of $996 million, which continues to be impacted by COVID, particularly in China. However, we continued to focus on growing revenue of Symbicort as well as Breztri following the successful additions to the NRDL.

Symbicort 的銷售額強勁，達到 27 億美元，年增長率為 10%。由於孤兒仿製藥和彈性 ICS/LABA 市場推出後的需求增長，美國的增長尤為強勁，增長 23% 至 10 億美元。在全球範圍內，信必可在 ICS/LABA 類別中的價值和數量市場份額方面仍然處於領先地位。 Pulmicort 在這一年下降了 32%，收入為 9.96 億美元，這繼續受到 COVID 的影響，尤其是在中國。然而，在成功加入 NRDL 後，我們繼續關注 Symbicort 和 Breztri 的收入增長。

Please turn to Slide 17. Now I will focus on the new launch medicines.

請轉到幻燈片 17。現在我將重點介紹新上市的藥物。

Fasenra contributed $949 million of revenue in the year, with strong growth despite COVID-19, with the majority continuing to come from the U.S., Germany and Japan. In the United States, Fasenra is now the leading novel biologic, up by 25%, with $603 million in revenue. Fasenra also overtook the leading IL-5-blocking medicine in total asthma prescriptions for the first time. Europe and Japan revenues were $203 million and $100 million, respectively, as Fasenra continued to be the leading novel biologic medicine for severe uncontrolled asthma.

Fasenra 在這一年貢獻了 9.49 億美元的收入，儘管有 COVID-19，但增長強勁，其中大部分繼續來自美國、德國和日本。在美國，Fasenra 現在是領先的新型生物製劑，增長了 25%，收入為 6.03 億美元。 Fasenra 還首次在總哮喘處方中超過了領先的 IL-5 阻斷藥物。歐洲和日本的收入分別為 2.03 億美元和 1 億美元，因為 Fasenra 仍然是嚴重未控制哮喘的領先新型生物藥物。

The launch of Breztri for COPD is progressing well with revenue of $28 million in the year, with launches taking place in Japan, China and the U.S. and more recently in the EU.

用於 COPD 的 Breztri 的推出進展順利，當年收入為 2800 萬美元，在日本、中國和美國以及最近在歐盟推出。

As we look to kidney disease, for Lokelma, we continue our leadership in the new-to-brand prescriptions; and with revenue of $76 million in the year, predominantly from the U.S. at $57 million. We have seen early sales in China, and the Japan launch is progressing well. On roxadustat, we reported collaboration revenue of $30 million in the year coming from China. Demand continues to remain strong as tens of thousands of patients are being treated for anemia in CKD with roxadustat. We now anticipate the U.S. regulatory decision in quarter 1 following the submission of the additional clarifying analysis data with the U.S. FDA.

當我們關注腎臟疾病時，對於 Lokelma，我們繼續在新品牌處方方面處於領先地位；當年收入為 7600 萬美元，主要來自美國，收入為 5700 萬美元。我們已經看到在中國的早期銷售，日本的發布進展順利。在 roxadustat 上，我們報告了當年來自中國的合作收入 3000 萬美元。由於成千上萬的 CKD 患者正在接受羅沙司他貧血治療，因此需求繼續保持強勁。我們現在預計在向美國 FDA 提交額外的澄清分析數據後，美國將在第一季度做出監管決定。

Please turn to Slide 18. Emerging Markets, where revenue grew by 10% in the year, continued to track ahead of our long-term performance ambition, which is to grow sales on average by a mid- to high single-digit percentage despite a slight negative effect from divestments. Outside China, total revenue was up by 9%, with growth spread across the regions. China delivered resilient growth at 11%; and continued to see some impact from the COVID-19 pandemic, notably with Pulmicort, as previously mentioned, and continued volume-based procurement impacts. We were very encouraged to successfully negotiate several medicines onto the China NRDL program for this coming year.

請轉到幻燈片 18。新興市場的收入在這一年增長了 10%，繼續領先於我們的長期業績目標，即儘管銷售額平均增長了中高個位數百分比。剝離帶來的輕微負面影響。在中國以外地區，總收入增長了 9%，增長分佈在各個地區。中國實現了 11% 的彈性增長；並繼續看到 COVID-19大流行的一些影響，特別是如前所述的 Pulmicort，以及持續的基於數量的採購影響。我們很受鼓舞，能夠成功談判將幾種藥物納入來年的中國 NRDL 計劃。

New medicines grew by 59%, now contributed 1/3 of total revenue in the region, with the stronger performance driven by Oncology and New CVRM.

新藥增長了 59%，目前貢獻了該地區總收入的 1/3，在腫瘤學和新 CVRM 的推動下表現更強勁。

With this, I will hand over to Marc. Please turn to Slide 19.

有了這個，我將交給馬克。請轉到幻燈片 19。

Thank you, Ruud. And hello, everyone.

謝謝你，魯德。大家好。

I want to take you through our financial performance in the year as well as the guidance for 2021. Please turn to Slide 20. As always, I will start with the reported P&L before commenting on our core results.

我想向您介紹一下我們今年的財務業績以及 2021 年的指導意見。請轉到幻燈片 20。一如既往，在評論我們的核心業績之前，我將從報告的損益開始。

As Pascal mentioned earlier, total revenue grew by 10% in the year, in line with the guidance I provided 12 months ago. In February last year, we did not know how much and how long the adverse net impact of COVID-19 was going to be. Within total revenue, product sales were up by 11%, driven by the success of the new medicines, with the majority of collaboration revenue reflected milestone receipts in respect of Lynparza.

正如 Pascal 之前提到的，今年總收入增長了 10%，這與我 12 個月前提供的指導一致。去年 2 月，我們不知道 COVID-19 的負面淨影響會有多大和多長時間。在總收入中，受新藥成功的推動，產品銷售額增長了 11%，其中大部分合作收入反映了 Lynparza 的里程碑式收入。

Please turn to Slide 21. Turning now to the core P&L, this slide demonstrates the progression of our operating leverage. Our gross margin ratio was unchanged in the year at 80%, in line with the expectation outlined last year. Our mix of sales is continually improving, but this was offset in the year by increasing pricing pressures in China related to the impact of the NRDL and the VBP program, to which Ruud alluded earlier.

請轉到幻燈片 21。現在轉到核心損益表，這張幻燈片展示了我們經營槓桿的進展。我們的毛利率在年內保持在 80% 不變，符合去年概述的預期。我們的銷售組合在不斷改善，但這在今年被與 NRDL 和 VBP 計劃的影響相關的中國定價壓力增加所抵消，Ruud 早些時候提到了這一點。

Core R&D expenses increased by 10%, partly a result of more investment in the pipeline, including Phase III trial starts for a number of medicine, including the oral SERD and the advancement of datopotamab deruxtecan also known as 1062. Merck upfront contribution in 2017 for the development of Lynparza recorded at that time on our balance sheet was gradually released to the P&L until 2019. This impacted the comparative performance in 2020. There was also a material investment in the development of brazikumab, although we are refunded for those costs through other operating income. Core SG&A expenses increased by 4%, driven by more investment in the China expansion and the launches of new medicines.

核心研發費用增加了 10%，部分原因是對管線的投資增加，包括許多藥物的 III 期試驗開始，包括口服 SERD 和 datopotamab deruxtecan（也稱為 1062）的進步。默克公司 2017 年的預付款用於當時記錄在我們資產負債表上的 Lynparza 的開發逐漸釋放到損益表中，直到 2019 年。這影響了 2020 年的比較業績。在開發 brazikumab 方面也有重大投資，儘管我們通過其他方式退還了這些成本營業收入。核心 SG&A 費用增長了 4%，這主要是由於對中國擴張的更多投資和新藥的推出。

Core other operating income declined by 2%, while the core tax rate was 20%.

其他核心營業收入下降 2%，而核心稅率為 20%。

Finally, our core earnings per share ended at $4.02, up by 18%, demonstrating the sustained progress we are making.

最後，我們的核心每股收益為 4.02 美元，增長 18%，表明我們正在取得持續的進步。

Please turn to Slide 22. Before we look at net debt and cash generation, I want to take a moment to reconfirm the changing shape of our P&L. While we expect collaboration revenue to increase over time and also anticipate that income from divestments will remain a material part of our P&L, this slide highlights the change in the sources of profit over the long term and the growing contribution from product sales that is being made from our new medicine, and I expect this trend to continue.

請轉到幻燈片 22。在我們查看淨債務和現金生成之前，我想花點時間再次確認我們損益表的變化形狀。雖然我們預計合作收入會隨著時間的推移而增加，並且預計撤資收入仍將是我們損益表的重要組成部分，但這張幻燈片強調了長期利潤來源的變化以及產品銷售的貢獻不斷增加來自我們的新藥，我預計這種趨勢將繼續下去。

Now turning to net debt. It was broadly unchanged in the year. A 27% improvement in EBITDA to $8.3 billion meant we took our net debt-to-EBITDA ratio from 1.8x to 1.5x. The strong growth of EBITDA was offset by a number of factors, including dividend payments totaling $3.6 billion. And we also made the second of our 2 $675 million upfront payment to Daiichi Sankyo in respect of Enhertu. Finally, we also paid the first noncontingent payment of $350 million also to Daiichi Sankyo as part of the agreement of datopotamab deruxtecan.

現在轉向淨債務。年內基本沒有變化。 EBITDA 增長 27% 至 83 億美元，這意味著我們將淨債務與 EBITDA 的比率從 1.8 倍提高到 1.5 倍。 EBITDA 的強勁增長被多種因素所抵消，其中包括總計 36 億美元的股息支付。我們還就 Enhertu 向 Daiichi Sankyo 支付了 6.75 億美元的第二筆預付款。最後，作為 datopotamab deruxtecan 協議的一部分，我們還向 Daiichi Sankyo 支付了第一筆 3.5 億美元的非或有款項。

I was pleased to see that our constantly improving business performance drove a significant year-on-year increase in net cash flow from operating activities. Even excluding the benefit of net cash inflows from vaccine activity, our cash from operating activities increased by around $800 million. The $1.1 billion of vaccine net cash flow are expected to reverse out in the near term. Our progress bodes well for ongoing ambition of converting improvements in operating leverage into increasing levels of cash.

欣喜地看到，不斷提升的經營業績帶動經營活動產生的現金流量淨額同比大幅增長。即使不包括疫苗活動產生的淨現金流入，我們的經營活動現金也增加了約 8 億美元。 11 億美元的疫苗淨現金流預計將在短期內逆轉。我們的進展預示著將經營槓桿的改善轉化為增加現金水平的持續雄心。

Please turn to Slide 23. This familiar slide summarizes the continued progress we are making with our financial priorities. As I mentioned, the 10% growth in total revenue in the year was converted into an 18% increase in core earnings per share. Our core operating margin rose by 2 more percentage points to 28% despite the reductions in collaboration revenue and other income. The progress on operating leverage was also demonstrated by the fact that core operating expenses represented 59% of total revenue versus 60% a year ago. As I said, this increasing level of profitability will convert into more cash that will help us deleverage our balance sheet; and help us to remain focused on the capital allocation priorities of reinvestment, the progressive dividend policy and a strong investment-grade credit rating.

請轉到幻燈片 23。這張熟悉的幻燈片總結了我們在財務優先事項方面取得的持續進展。正如我所提到的，當年總收入增長 10% 轉化為每股核心收益增長 18%。儘管合作收入和其他收入有所減少，但我們的核心營業利潤率又上升了 2 個百分點，達到 28%。核心運營支出佔總收入的 59%，而一年前為 60%，這一事實也證明了經營槓桿的進步。正如我所說，這種不斷提高的盈利水平將轉化為更多現金，幫助我們去槓桿化我們的資產負債表；並幫助我們繼續專注於再投資的資本配置優先事項、漸進式股息政策和強大的投資級信用評級。

Please turn to Slide 24. Finally, I will turn to guidance for 2021, which as I mentioned a moment ago is on total revenue and core earnings per share at constant exchange rates. It does not reflect any revenue or profit impact from sales of the COVID-19 Vaccine AstraZeneca or any impact from the proposed acquisition of Alexion.

請轉到幻燈片 24。最後，我將轉向 2021 年的指導，正如我剛才提到的，這是按固定匯率計算的總收入和每股核心收益。它不反映 COVID-19疫苗阿斯利康銷售的任何收入或利潤影響或擬議收購 Alexion 的任何影響。

I am confident in our guidance, despite the uncertainties arising from the pandemic, of a low-teens percentage increase in total revenue, with even faster growth in core EPS to between $4.75 and $5. The confidence is based on the success of our patient-centric strategy, the focus on innovation and our track record of commercial execution.

儘管大流行帶來了不確定性，但我對我們的指導充滿信心，總收入增長百分比較低，核心每股收益增長更快，達到 4.75 美元至 5 美元之間。這種信心基於我們以患者為中心的戰略的成功、對創新的關注以及我們在商業執行方面的記錄。

Please turn to Slide 25. And finally, I want to echo Pascal's comment on the proposed acquisition of Alexion. This transition is intended to drive both a strategic and financial development of our business. The case for scientific and business complementarity is clear, with the acquisition enabling us to develop our immunology business further, utilize our emerging market presence further and help Alexion develop better rare disease medicine using our platforms. We are very excited about the prospect of combining 2 science and patient-centric organization, deliver further sustained industry-leading revenue growth.

請翻到幻燈片 25。最後，我想重複 Pascal 對擬議收購 Alexion 的評論。這種轉變旨在推動我們業務的戰略和財務發展。科學和業務互補的理由很明確，此次收購使我們能夠進一步發展我們的免疫學業務，進一步利用我們的新興市場影響力，並幫助 Alexion 使用我們的平台開發更好的罕見病藥物。我們對結合 2 科學和以患者為中心的組織的前景感到非常興奮，進一步實現行業領先的持續收入增長。

As you will have seen from our track record and from our guidance, we are making good progress on revenue growth and operating leverage, which is driving greater level of cash generation. This strategic, compelling acquisition is intended to build on these prospects based, as they are, on the focus on science and innovation.

正如您從我們的業績記錄和我們的指導中看到的那樣，我們在收入增長和經營槓桿方面取得了良好進展，這正在推動更高水平的現金產生。這一戰略性的、引人注目的收購旨在基於對科學和創新的關注，在這些前景的基礎上再接再厲。

Thank you for listening. And with that, I will now hand over to Mene. Please turn to Slide 26.

謝謝你的聆聽。有了這個，我現在將交給梅內。請轉到幻燈片 26。

Thank you, Marc. And hello, everyone.

謝謝你，馬克。大家好。

I'll now provide an update on our COVID-19 efforts and our BioPharmaceuticals medicines since the last quarter. I'm also joined by Dave Fredrickson, covering for José Baselga, who will discuss Oncology movements and upcoming news flow across the company. Please turn to Slide 27.

我現在將提供自上個季度以來我們的 COVID-19 工作和我們的生物製藥藥物的最新情況。 Dave Fredrickson 也加入了我的行列，為 José Baselga 做報導，他將討論整個公司的腫瘤學運動和即將到來的新聞流。請轉到幻燈片 27。

In December of 2020, our vaccine received its first authorization for emergency supply from the U.K. MHRA. With recent conditional marketing authorization from the EMA, we are now authorized with this vaccine in over 50 countries. Yesterday, we also received a positive recommendation for the vaccine from the WHO's SAGE group. This is a really important milestone ahead of an emergency use listing by the WHO, which should it be granted would provide an accelerated pathway to significantly broaden availability of the vaccine around the world. And I think it's important to not forget that, from when the agreement was signed with Oxford University through the first approval, only 8 months have elapsed. Now just over 9 months away, we have the vaccine approved in more than 1/4 of all countries around the world.

2020 年 12 月，我們的疫苗首次獲得英國 MHRA 的緊急供應授權。憑藉最近獲得 EMA 的有條件營銷授權，我們現在已獲准在 50 多個國家/地區使用該疫苗。昨天，我們還收到了世界衛生組織SAGE小組對該疫苗的積極推薦。這是 WHO 緊急使用清單之前的一個非常重要的里程碑，如果獲得批准，這將提供一條加速途徑，以顯著擴大疫苗在世界範圍內的可用性。而且我認為不要忘記，從與牛津大學簽署協議到首次批准，僅過去了8個月。現在僅剩 9 個多月的時間，我們的疫苗已在全球超過 1/4 的國家/地區獲得批准。

We've recently also published data on the impact of the emerging U.K. Kent and South African variants. The vaccine is as effective against the new U.K. variant as it is against the original strain despite some lower neutralizing activity. The South African strain resulted in a loss of efficacy against mild disease but may still offer protection against severe disease, which is key to relieving the burden on health care resources around the world. We've also begun work on adapting the vaccine for these new variants of concern, leveraging our existing clinical trial data and an established supply chain to potentially reduce the time needed to reach production at scale. Finally, we also presented our primary pooled analysis of the pooled Oxford trials and recently published in a Lancet preprint. The analysis showed good efficacy after the first dose, with over 70%; confirmed increased efficacy with a longer dosing interval, rising to 82% at 12 weeks and up; and confirmed a 100% protection against severe disease and hospitalization. Data readout from the U.S. trial is anticipated before the end of this quarter.

我們最近還發布了有關新興的英國肯特和南非變種的影響的數據。儘管中和活性較低，但該疫苗對新的英國變種和原始毒株一樣有效。南非菌株導致對輕度疾病的療效喪失，但仍可提供針對嚴重疾病的保護，這是減輕全球醫療資源負擔的關鍵。我們還開始著手針對這些令人擔憂的新變種調整疫苗，利用我們現有的臨床試驗數據和已建立的供應鏈，以潛在地減少實現大規模生產所需的時間。最後，我們還介紹了我們對匯總的牛津試驗的主要匯總分析，並且最近發表在《柳葉刀》預印本上。分析顯示首劑療效良好，達70%以上；確認延長給藥間隔可提高療效，在 12 週及以上時提高至 82%；並確認 100% 保護免受嚴重疾病和住院治療。美國試驗的數據預計將在本季度末之前公佈。

Turning to our long-acting antibody AZD7442. We feel this has a differentiated profile due to its high potency, its extended half-life and its capacity to be used either as an intramuscular administration or intravenous. It is now running in 5 Phase III trials. Early in vitro data from a couple of independent laboratories have suggested good neutralizing activity against U.K. and South African strains, with potentially class-leading activity for this combination against these strains.

轉向我們的長效抗體 AZD7442。我們認為，由於其高效力、延長的半衰期以及可用作肌肉內給藥或靜脈內給藥的能力，我們認為它具有差異化特徵。它現在正在進行 5 項 III 期試驗。來自幾個獨立實驗室的早期體外數據表明對英國和南非毒株具有良好的中和活性，這種組合對這些毒株具有潛在的一流活性。

Please return -- turn to Slide 28. We have several medicines that have the potential to establish a new standard of care for patients in need.

請返回——轉到幻燈片 28。我們有幾種藥物有可能為有需要的患者建立新的護理標準。

In CVRM, Farxiga has moved beyond type 2 diabetes and into 2 new disease areas with high mortality and a large unmet medical need. Farxiga is now approved for patients with heart failure with reduced ejection fraction in the United States, the EU, China and Japan. And its CKD indication recently received priority review in the U.S. and Japan. Farxiga truly has the opportunity to redefine treatment as the first medicine to significantly prolong survival in patients with heart failure with reduced ejection fraction and also now in CKD with or without type 2 diabetes.

在 CVRM 中， Farxiga 已經超越了 2 型糖尿病，進入了 2 個死亡率高和醫療需求未得到滿足的新疾病領域。 Farxiga 現已在美國、歐盟、中國和日本獲准用於射血分數降低的心力衰竭患者。其 CKD 適應症最近在美國和日本獲得了優先審評。 Farxiga 真正有機會重新定義治療，作為第一種顯著延長射血分數降低的心力衰竭患者以及現在伴有或不伴有 2 型糖尿病的 CKD 患者生存期的藥物。

In terms of upcoming news for Farxiga, we have just started a new trial in the post-MI setting, called DAPA-MI, where we will explore whether providing Farxiga within 7 days post MI will be able to reduce hospitalization for heart failure or CV death in nondiabetic patients with reduced left ventricular ejection fraction. We also have trial starts this quarter for our Farxiga combination programs both with AZD9977 and zibotentan. Lastly, in the second half of the year, we will have data from the DELIVER trial in patients with heart failure with preserved ejection fraction.

關於 Farxiga 即將發布的消息，我們剛剛開始了一項名為 DAPA-MI 的 MI 後設置的新試驗，我們將在其中探索在 MI 後 7 天內提供 Farxiga 是否能夠減少因心力衰竭或 CV 住院左心室射血分數降低的非糖尿病患者死亡。本季度我們還開始了 Farxiga 與 AZD9977 和 zibotentan 聯合方案的試驗。最後，在今年下半年，我們將獲得射血分數保留的心力衰竭患者的 DELIVER 試驗數據。

Please turn to Slide 29. Anifrolumab is our first-in-class interferon 1 medicine for the treatment of patients with moderate to severe systemic lupus erythematosus. It has potential to bring hope to a set of patients who have been chronically underserved for over a decade. Anifrolumab has demonstrated consistent clinical benefits across all measured SLE patient subgroups, showing early and sustained reduction in skin disease activity, improvements across a number of organs; and enabling importantly sustained steroid use reduction. Regulatory submissions have been completed in the U.S., the EU and Japan; and we anticipate the first regulatory decisions in the second half of this year. We also have a number of life cycle management indications planned to include lupus nephritis, cutaneous lupus erythematosus and myositis, which illustrate our excitement about the future of our efforts in the immunology space.

請轉到幻燈片 29。Anifrolumab 是我們用於治療中度至重度系統性紅斑狼瘡患者的一流乾擾素 1 藥物。它有可能為十多年來長期得不到治療的一組患者帶來希望。 Anifrolumab 已在所有測量的 SLE 患者亞組中顯示出一致的臨床益處，顯示出皮膚病活動的早期和持續減少，以及多個器官的改善；並使重要的是持續減少類固醇的使用。已在美國、歐盟和日本完成監管提交；我們預計將在今年下半年做出第一個監管決定。我們還計劃了一些生命週期管理適應症，包括狼瘡性腎炎、皮膚紅斑狼瘡和肌炎，這表明我們對免疫學領域未來的努力感到興奮。

Please turn to Slide 30. I'll now update you on progress in our pipeline. In Respiratory, I'd like to mention that the exciting NAVIGATOR Phase III trial data for tezepelumab in severe asthma will be presented at the AAAAI at the end of the month. Our IL-33 antibody MEDI3506 has now started Phase II trials in asthma and also in diabetic kidney disease. Continuing, on the renal space, our FLAP inhibitor AZD5718 has also made progress having started Phase II trials in CKD. And as I mentioned earlier, the first of our Farxiga life cycle [expanding combination] programs with our MC -- MR modulator AZD9977 is initiating Phase II trials in heart failure with CKD. Lastly, our subcutaneous PCSK9 program AZD8233 started its Phase IIb trials in dyslipidemia and the trial continues at pace.

請轉到幻燈片 30。我現在將向您介紹我們管道的最新進展。在呼吸方面，我想提一下，tezepelumab 在嚴重哮喘中的令人興奮的 NAVIGATOR III 期試驗數據將於月底在 AAAAI 上公佈。我們的 IL-33 抗體 MEDI3506 現已開始針對哮喘和糖尿病腎病的 II 期試驗。繼續，在腎臟空間，我們的 FLAP 抑製劑 AZD5718 也取得了進展，開始了 CKD 的 II 期試驗。正如我之前提到的，我們的第一個 Farxiga 生命週期[擴展組合]項目與我們的 MC -- MR 調製器 AZD9977 正在啟動 CKD 心力衰竭的 II 期試驗。最後，我們的皮下 PCSK9 項目 AZD8233 開始了其針對血脂異常的 IIb 期試驗，並且該試驗將繼續進行。

We look forward to updating you on the progress of all of our medicines in the BioPharmaceuticals pipeline over the coming year.

我們期待著在來年向您通報我們所有藥物在生物製藥管線中的最新進展。

I'll now hand over to Dave, and please turn to Slide 31.

我現在將交給 Dave，請轉到幻燈片 31。

Thank you, Mene. And hello again.

謝謝你，梅內。再次你好。

I'm happy to take you through Oncology R&D news this quarter, and I'll start with Tagrisso to continue on the theme of establishing a new standard of care for patients.

我很高興為您介紹本季度的腫瘤研發新聞，我將從 Tagrisso 開始，繼續探討為患者建立新的護理標準這一主題。

The groundbreaking ADAURA Phase III data has further confirmed Tagrisso's capability to reshape future clinical practice. We recently received regulatory approval in the U.S. as well as approvals in 4 other countries as a result of project Orbis, a new review process by FDA and other agencies, and now have further submissions underway in this potentially curative setting. Starting with its approval in 2015 from the Phase III AURA3 trial and second-line T790M, we've since brought Tagrisso to first line in a broader setting with the FLAURA trial by demonstrating an overall survival benefit. Now with the ADAURA data exhibiting around an 80% reduction in the risk of disease recurrence or death, Tagrisso is the only medicine to show meaningful benefit in adjuvant eGFR-mutated non-small cell lung cancer. Tagrisso's trajectory is an excellent example of the efforts we're making across our portfolio in Oncology. Our aim is to establish new standards of care for patients, with a concerted effort in earlier stages of disease.

突破性的 ADAURA III 期數據進一步證實了 Tagrisso 重塑未來臨床實踐的能力。由於 Orbis 項目（FDA 和其他機構的新審查程序），我們最近在美國獲得了監管批准，並在其他 4 個國家/地區獲得了批准，現在正在就這一潛在的治療環境提交進一步的申請。從 2015 年 III 期 AURA3 試驗和二線 T790M 獲得批准開始，我們已經通過 FLAURA 試驗證明了總體生存益處，將 Tagrisso 帶到更廣泛的一線。現在，隨著 ADAURA 數據顯示疾病復發或死亡風險降低約 80%，Tagrisso 是唯一一種在 eGFR 突變的非小細胞肺癌輔助治療中顯示出有意義益處的藥物。 Tagrisso 的軌跡是我們在腫瘤學產品組合中所做努力的一個很好的例子。我們的目標是在疾病的早期階段共同努力，為患者建立新的護理標準。

Please turn to Slide 32, moving on to Calquence, a selective BTKi that has shown impressive effectiveness in chronic lymphocytic leukemia. Calquence has delivered unprecedentedly low hazard ratios in both the relapsed/refractory and in the front line settings, within the latter showing efficacy as both a monotherapy and in combination with immunochemotherapy. We recently announced high-level results from the ELEVATE-RR trial, which showed that Calquence met the primary end point of non-inferior progression-free survival for adults with previously treated high-risk CLL versus ibrutinib. In addition, with over 40 months of follow-up, Calquence demonstrated superior safety in atrial fibrillation without compromising efficacy. We look forward to discussing the totality of the data which confirm our confidence in Calquence's favorable benefit-risk profile with global health authorities.

請轉到幻燈片 32，轉到 Calquence，這是一種選擇性 BTKi，已在慢性淋巴細胞白血病中顯示出令人印象深刻的療效。 Calquence 在復發/難治性和前線設置中都提供了前所未有的低風險比，在前線設置中，後者顯示出作為單一療法和與免疫化療聯合療法的療效。我們最近公佈了 ELEVATE-RR 試驗的高水平結果，該試驗表明，與依魯替尼相比，Calquence 達到了既往接受過治療的高危 CLL 成人的非劣效無進展生存期的主要終點。此外，經過 40 多個月的隨訪，Calquence 在不影響療效的情況下證明了房顫的卓越安全性。我們期待著與全球衛生當局討論所有數據，這些數據證實了我們對 Calquence 有利的收益-風險狀況的信心。

Please turn to Slide 33. Now I'll provide a short pipeline update with a focus on the key movements in the quarter.

請轉到幻燈片 33。現在我將提供一個簡短的管道更新，重點是本季度的關鍵動作。

Our TROP2 ADC datopotamab deruxtecan that we develop and will commercialize in combination with Daiichi Sankyo has started Phase III trials in non-small cell lung cancer, building on the efficacy seen in the TROPION-PanTumor01 trial that was recently presented at the World Conference on Lung Cancer in January. In addition, we've initiated Phase III trials for AZD9833, our next-generation SERD now known as camizestrant. We look forward to updating you on the progress of these medicines and others in the near future.

我們開發的 TROP2 ADC datopotamab deruxtecan 將與 Daiichi Sankyo 聯合開發並將商業化，該藥物已開始在非小細胞肺癌中進行 III 期試驗，該試驗建立在最近在世界肺臟大會上展示的 TROPION-PanTumor01 試驗中所見療效的基礎上一月巨蟹座。此外，我們已經啟動了 AZD9833 的 III 期試驗，我們的下一代 SERD 現在稱為 camistrant。我們期待在不久的將來向您通報這些藥物和其他藥物的最新進展。

Please turn to Slide 34. I'll end by taking you through some key items of anticipated news flow in 2021 across our entire pipeline. In Oncology, we will see Phase III data readouts for Lynparza's OlympiA trial in adjuvant breast cancer and the PROpel trial in prostate cancer as well as Imfinzi's PACIFIC-2 trial in non-small cell lung cancer and overall survival data from the POSEIDON trial. For Enhertu, we'll have data from DESTINY-Breast03, which is a head-to-head trial in the second line versus trastuzumab emtansine; as well as data from DESTINY-Breast04 in HER2-low breast cancer.

請轉到幻燈片 34。最後，我將帶您了解 2021 年我們整個管道中預期新聞流的一些關鍵項目。在腫瘤學方面，我們將看到 Lynparza 的 OlympiA 輔助乳腺癌試驗和 PROpel 前列腺癌試驗的 III 期數據讀數，以及 Imfinzi 的非小細胞肺癌 PACIFIC-2 試驗和 POSEIDON 試驗的總生存數據。對於 Enhertu，我們將獲得 DESTINY-Breast03 的數據，這是一項二線與曲妥珠單抗 emtansine 的頭對頭試驗；以及來自 DESTINY-Breast04 在 HER2-low 乳腺癌中的數據。

In BioPharmaceuticals, we'll have regulatory submissions for tezepelumab in severe asthma as well as regulatory decisions for anifrolumab and for roxadustat. Finally, as mentioned earlier by Mene, we will have data readouts for both the AstraZeneca COVID-19 vaccine U.S. Phase III trial as well as the first data readouts from the long-acting antibody AZD7442.

在 BioPharmaceuticals 中，我們將提交 tezepelumab 治療嚴重哮喘的監管意見書，以及 anifrolumab 和 roxadustat 的監管決定。最後，正如 Mene 之前提到的，我們將獲得阿斯利康 COVID-19 疫苗美國 III 期試驗的數據讀數以及長效抗體 AZD7442 的首批數據讀數。

With that said, I'll now hand it back to Pascal for closing comments. Please turn to Slide 35.

話雖如此，我現在將把它交還給 Pascal 以徵求結束意見。請轉到幻燈片 35。

Thank you, Dave.

謝謝你，戴夫。

Please turn to Slide 36. In 2020, performance was strong and resilient and we delivered the guidance as promised. The 10% increase in revenue was underpinned by the focused R&D and SG&A investments and despite headwind from the pandemic in many parts of our global business. New medicines were up by 33%, and we saw continued performance from Oncology and New CVRM. Respi and immunology was stable but improved a lot in the quarter. And Emerging Markets were up by 10%, with growth impacted by COVID-19 on Pulmicort, I think we told you, but Respiratory & Immunology would have grown by 12% due to neutralize the effect on Pulmicort.

請轉到幻燈片 36。2020 年，業績強勁且富有彈性，我們按照承諾交付了指導。收入增長 10% 的基礎是集中的研發和 SG&A 投資，儘管我們全球業務的許多部分都受到大流行的不利影響。新藥增長了 33%，我們看到腫瘤學和新 CVRM 的持續表現。 Respi 和免疫學穩定，但在本季度有很大改善。新興市場增長了 10%，增長受到 COVID-19 對 Pulmicort 的影響，我想我們告訴過你，但由於中和了對 Pulmicort 的影響，呼吸和免疫學將增長 12%。

Core operating profit grew by 17% despite 2% lower core operating income. With a tax rate of 20%, core EPS ended at $4.02, up by 18% and more than revenue, delivering operating leverage. As a result, guidance was achieved as we promised. Our cash flow is improving, including '19 cash inflow from operating activities, that are now $4.8 billion and support the progressive dividend policy.

儘管核心營業收入下降了 2%，但核心營業利潤增長了 17%。在稅率為 20% 的情況下，核心 EPS 收於 4.02 美元，增長 18%，超過收入，提供經營槓桿。結果，指導如我們所承諾的那樣實現了。我們的現金流正在改善，包括 19 年來自經營活動的現金流入，現在為 48 億美元，支持漸進式股息政策。

We continue to see strong progress in the pipeline, mostly on approvals, supporting sales today and, of course, tomorrow. This year, we are back with more Phase III trial readouts like Calquence recently. The efforts against the COVID-19 pandemic continued with the first authorization for the vaccine. Let me assure the -- everyone today that we are doing our very best to deliver it to governments as promised. During this first half, we anticipate Phase III data also for the long-acting antibody combination, the potential new medicine AZD7442, which you've heard through this presentation is a very exciting product.

我們繼續看到管道中的強勁進展，主要是在批准方面，支持今天和明天的銷售。今年，我們回來了更多的 III 期試驗讀數，比如最近的 Calquence。隨著疫苗的首次授權，抗擊 COVID-19 大流行的努力繼續進行。讓我向今天的每個人保證，我們正在盡最大努力按照承諾將其交付給政府。在上半年，我們預計長效抗體組合的 III 期數據，即潛在的新藥 AZD7442，您已經通過本次演示了解到這是一個非常令人興奮的產品。

In 2021, we anticipate another year of double-digit revenue growth in the low teens, with that revenue growth accompanied by even faster growth in core EPS to between $4.75 and $5, all of these at constant exchange rates.

到 2021 年，我們預計青少年收入將再次實現兩位數增長，收入增長伴隨著核心每股收益更快增長，達到 4.75 美元至 5 美元之間，所有這些均按固定匯率計算。

So let's now go to the Q&A. (Operator Instructions) We will also take written questions from the webcast. (Operator Instructions) Thank you, in advance, for this. And perhaps now we can take the first question from the conference call.

現在讓我們進入問答環節。 （操作員說明）我們還將接受網絡廣播中的書面問題。 （操作員說明）在此先感謝您。也許現在我們可以回答電話會議中的第一個問題。

And the first question, I believe, is from Mark

我相信第一個問題來自 Mark

(technical difficulty)

（技術難度）

Hello. Can you here me, Pascal?

你好。你能在這裡嗎，帕斯卡？

Yes, we can hear you, yes.

是的，我們能聽到你的聲音，是的。

Great. The subject is investing for growth, Pascal. Can you sort of help us understand and sort of frame the elements here? For example, on R&D, how are you going to prioritize the various pipeline assets that you have after the Alexion acquisition closes and you have a sort of wall of "what's next" opportunities but with more financial flexibility? I sort of counted 10 in Oncology, 12 in biopharma. And you mentioned 11 in Alexion as well. And how you should -- and in terms of investing for growth also, how we should think about the SG&A components of that. And that leads then to -- specifically on to anifrolumab, if I may. 250,000 diagnosed lupus patients in the U.S. every year, only 25,000 on Benlysta, so can you sort of help us understand how physicians will choose to use anifrolumab relative to, say, immunosuppressants or Benlysta or Rituxan? And the progress there with the subcutaneous formulation which you're also investing in as well.

偉大的。主題是為增長而投資，帕斯卡。你能幫助我們理解並組織這裡的元素嗎？例如，在研發方面，在 Alexion 收購完成後，您將如何優先考慮您擁有的各種管道資產，並且您擁有一堵“下一步是什麼”的機會，但具有更大的財務靈活性？我算了一下，腫瘤學有 10 個，生物製藥學有 12 個。你在 Alexion 中也提到了 11。以及你應該如何 - 以及在投資增長方面，我們應該如何考慮其中的 SG&A 組成部分。然後，如果可以的話，這會導致——特別是 anifrolumab。美國每年有 250,000 名診斷出狼瘡患者，只有 25,000 名患者使用 Benlysta，那麼您能否幫助我們了解醫生將如何選擇使用 anifrolumab 相對於免疫抑製劑或 Benlysta 或 Rituxan？還有你也在投資的皮下製劑的進展。

Thanks, Mark. So on the anifrolumab question, maybe Mene, a little bit later, you can cover the subcu formulation. And Ruud, you could cover the positioning and basically the commercial opportunity. So let me first cover the first question, Mark. It's you've said it. We have a pretty strong pipeline and large portfolio. And that's why we believe we need to continue investing in R&D in particular, also a little bit in SG&A but much less, of course, because we have a strong infrastructure globally already, but certainly in R&D we'll continue to invest. We want to drive top line. I mean basically we have 2 goals. One is to drive the top line as fast as possible, and the second is to continue delivering operating leverage over a period of time. So we'll [continue that]. In term of prioritization, essentially we have regular -- we have a regular portfolio meeting that looks at all these projects. We have -- twice a year, we review our overall pipeline. We have a strategy meeting typically in June, July where we look at all our projects and we compare them. And we compare and contrast, then we try to prioritize. And the team comes -- the teams come and then they present their projects, and we prioritize what they present to us. I mean there is nothing really special here. We look at the metrics that any other company would look at. I think what we're trying to do is have good discussions beyond the metrics and get to the bottom of the data and understand the data and challenge ourselves, and that's how we actually prioritize and then build our plan according to this. Really there is nothing different we do from other companies, except, I think, maybe spend a lot of time looking at the data, debating and going beyond the numbers that are presented to us. So with this, maybe Ruud, do you want to cover the anifrolumab question and hand over to Mene for the subcu?

謝謝，馬克。所以關於 anifrolumab 問題，也許 Mene，稍後，你可以討論 subcu 配方。而 Ruud，你可以涵蓋定位和基本上的商業機會。所以讓我先回答第一個問題，馬克。是你說了算我們擁有非常強大的管道和龐大的產品組合。這就是為什麼我們認為我們需要繼續投資研發，特別是在 SG&A 方面也有一點投資，但當然要少得多，因為我們已經在全球擁有強大的基礎設施，但我們肯定會繼續投資研發。我們想推動收入增長。我的意思是基本上我們有兩個目標。一是盡快推動收入增長，二是在一段時間內繼續發揮經營槓桿作用。所以我們將[繼續]。在確定優先級方面，基本上我們有定期的——我們有定期的投資組合會議來研究所有這些項目。我們每年兩次審查我們的整體管道。我們通常在 6 月、7 月舉行戰略會議，我們會審查所有項目並進行比較。我們比較和對比，然後我們嘗試確定優先順序。團隊來了——團隊來了，然後他們展示了他們的項目，我們優先考慮他們展示給我們的東西。我的意思是這裡沒有什麼特別的。我們查看任何其他公司都會查看的指標。我認為我們正在嘗試做的是在指標之外進行良好的討論，深入了解數據並理解數據並挑戰自己，這就是我們實際確定優先級並據此制定計劃的方式。事實上，我們所做的與其他公司沒有什麼不同，除了，我認為，可能會花很多時間查看數據、辯論和超越呈現給我們的數字。所以有了這個，也許 Ruud，你想解決 anifrolumab 問題並將 subcu 交給 Mene 嗎？

Of course, Pascal. And thanks, Mark, for the question. So first of all, we truly believe that interferon -- the interferon mechanism is central to SLE, and therefore we believe we can help a broad patient population. We have seen in our clinical trials that we clearly have a broad efficacy across multiple organs and -- but also multiple patient groups as well as a very impressive OCS reduction. I think one of the most important parts is that -- and physicians are giving that back, physicians who have experience with anifrolumab, about an early response. The current therapies are lacking in an early response, and both for physicians and patients it's very important to see a positive impact. So all in all, of course, we are doing an enormous amount of work as we speak so that we are ready to launch the product in the United States and in other geographies in the second half of the year, but it is a truly very attractive opportunity. And too many patients are still not getting well served as we speak. Clearly, you are referring to Benlysta. Overall, the penetration is still relatively limited, so we clearly see a huge opportunity moving forward here. Mene, are you going to cover the subcutaneous formulation?

當然，帕斯卡。馬克，謝謝你提出這個問題。因此，首先，我們真正相信干擾素——干擾素機制是 SLE 的核心，因此我們相信我們可以幫助廣大患者群體。我們在臨床試驗中已經看到，我們顯然在多個器官和多個患者群體中具有廣泛的療效，以及非常令人印象深刻的 OCS 減少。我認為最重要的部分之一是——醫生們正在回饋那些有 anifrolumab 經驗的醫生，關於早期反應。目前的療法缺乏早期反應，對於醫生和患者來說，看到積極的影響非常重要。所以總而言之，當然，我們正在做大量的工作，以便我們準備在今年下半年在美國和其他地區推出該產品，但這確實是一個非常有吸引力的機會。就在我們說話的時候，太多的病人仍然沒有得到很好的服務。很明顯，你指的是本利斯塔。總體而言，滲透率仍然相對有限，因此我們清楚地看到了向前發展的巨大機會。 Mene，你打算介紹皮下製劑嗎？

Yes. Thanks, Ruud. So with regards to subcu, we presented some data in 2019 on the subcu formulation, which was a PK/PD study which was very consistent with previous studies using our IV formulation. We haven't shared time lines for when we'll be pursuing subcu, but I can say that we are pursuing subcu formulations for anifro. And we will give you more concrete plans in terms of timing of launches as we have them.

是的。謝謝，魯德。因此，關於 subcu，我們在 2019 年提供了一些關於 subcu 製劑的數據，這是一項 PK/PD 研究，與之前使用我們的 IV 製劑的研究非常一致。我們還沒有分享我們何時會追求 subcu 的時間表，但我可以說我們正在追求 anifro 的 subcu 配方。我們將根據現有的發佈時間為您提供更具體的計劃。

Thanks, Mene. Richard Parkes, Exane BNP.

謝謝，梅內。理查德帕克斯，Exane BNP。

Hopefully, you can hear me okay...

希望你能聽到我的聲音...

Yes.

是的。

Yes, absolutely. Go ahead, Richard.

是的，一點沒錯。來吧，理查德。

So just sort of broadly sort of financial focused. Your revenue guidance for the year is a little bit more optimistic than consensus, so I wondered if you could give us a steer as to whether you think maybe consensus was too conservative in terms of revenues, but on the flip side it seems like your margin assumptions are a little bit lower. I'm assuming that's you simply taking a conscious opportunity to reinvest back in the business, so maybe you can just clarify that and [where] you expect to invest a little bit more aggressively than consensus has assumed.

所以只是有點廣泛地關注金融。你們今年的收入指引比共識樂觀一點，所以我想知道你是否可以指導我們是否認為共識在收入方面過於保守，但另一方面，你的利潤似乎假設有點低。我假設你只是有意識地抓住機會對業務進行再投資，所以也許你可以澄清這一點，以及你希望在[哪裡]進行比共識假設更積極的投資。

And if you don't mind me just taking a second one, on operating cash flow for 2020. If I exclude the benefit from the COVID vaccine funding, the improvement in operating cash flow is relatively modest, $800 million, despite a significant improvement in reported operating profit which was $2 billion plus, I think, incrementals. So can you help us clarify some of the moving parts there that's maybe continued to drag? And maybe give us a steer on the magnitude of free cash flow improvement in 2021 pre Daiichi payments.

如果你不介意我只拿第二個，關於 2020 年的運營現金流。如果我排除 COVID 疫苗資金的好處，儘管運營現金流有顯著改善，但運營現金流的改善相對溫和，為 8 億美元報告的營業利潤為 20 億美元，我認為還有增量。那麼你能幫我們澄清一些可能會繼續拖累的活動部分嗎？或許可以指導我們了解 2021 年 Daiichi 預付款中自由現金流改善的幅度。

Thanks, Richard. So maybe I'll try to cover the first couple of questions, and Marc can then add to these and also cover the cash flow question. So if we look at revenue: As you know, we don't guide or don't comment on a product-by-product basis, but I think you can see it. We have a very broad portfolio. We have a broad geographical coverage. And we've talked about it for a period, for quite a number of years now, but it's starting to have an impact. And so we have a very, very strong portfolio of products driving our top line. I can't really tell you, comment on one or the other product because we don't guide by product, but actually as it relates to your second question, we do continue to invest in R&D. We do continue to build a company that is fast growing in the near term but also has a long runway. Quite often, we are asked questions about succession as if some of us are getting quite old and ready to go, but I can tell you, despite our advanced age, it doesn't stop us from thinking long term. And so we will continue to invest in R&D. That's the core. That's the heart of our company, and that will continue driving this company in the future. Marc, do you want to add anything and [color] the cash flow question as well?

謝謝，理查德。所以也許我會嘗試涵蓋前幾個問題，然後馬克可以添加這些問題並涵蓋現金流量問題。因此，如果我們看一下收入：如您所知，我們不會在逐個產品的基礎上進行指導或評論，但我認為您可以看到它。我們擁有非常廣泛的產品組合。我們的地理覆蓋面很廣。我們已經討論了一段時間，現在已經很多年了，但它開始產生影響。因此，我們擁有非常非常強大的產品組合來推動我們的收入增長。我真的不能告訴你，對一個或另一個產品發表評論，因為我們不按產品指導，但實際上與你的第二個問題有關，我們確實繼續投資於研發。我們確實會繼續建立一家在短期內快速增長但也有很長跑道的公司。很多時候，我們會被問到有關繼任的問題，就好像我們中的一些人已經老了，準備好了，但我可以告訴你，儘管我們年事已高，但這並不能阻止我們考慮長遠。因此，我們將繼續投資於研發。這就是核心。這是我們公司的核心，它將在未來繼續推動這家公司的發展。馬克，你想補充什麼和 [顏色] 現金流量問題嗎？

Thank you, Richard, for the question on the cash flow. So if you look at the -- so we can look at the net cash flow at the bottom of the cash flow statement or we can look at other intermediary levels, but I would recommend that you look at the cash flow from 2 things; first of all, the cash flow from operations, which has grown in 2020 by $1.8 billion. You have signaled, because we have commented upon it, the part that is linked to the vaccine, the COVID vaccine. So the growth of the cash flow from operations was 62% including the vaccine but was also 26% excluding the vaccine. So the underlying business cash flow is growing -- cash from operation is growing faster than sales and faster than operating profit, so I think that's a very good sign. I would also recommend that you look at the progression of the EBITDA. We had an EBITDA in 2020 of $8.3 billion versus $6.7 billion in the comparative prior year, so an increase of $1.6 billion. So I think these 2, in my view, point to an improvement of profitability and an improvement in cash conversion.

謝謝你，理查德，關於現金流量的問題。因此，如果您查看 - 我們可以查看現金流量表底部的淨現金流量，或者我們可以查看其他中間級別，但我建議您從兩個方面查看現金流量；首先是運營產生的現金流，2020 年增長了 18 億美元。你已經發出信號，因為我們已經評論過與疫苗有關的部分，即 COVID 疫苗。因此，包括疫苗在內的運營現金流增長了 62%，但不包括疫苗也增長了 26%。因此，潛在的業務現金流正在增長——運營現金的增長速度快於銷售額，也快於營業利潤，所以我認為這是一個非常好的跡象。我還建議您查看 EBITDA 的進展情況。我們在 2020 年的 EBITDA 為 83 億美元，而去年同期為 67 億美元，因此增加了 16 億美元。所以我認為這兩個，在我看來，指向盈利能力的提高和現金轉換的改善。

Thank you, Marc. (Operator Instructions) Any other questions? Well, we have a question from Michael Leuchten at UBS.

謝謝你，馬克。 （操作員說明）還有其他問題嗎？好吧，瑞銀的 Michael Leuchten 提出了一個問題。

I'm going to stick to one, on Tagrisso in the adjuvant setting now that you have the companion listing and the approval. I'm just wondering if Dave could talk to the operational challenges that there may be in the setting moving patients from surgeons to oncologists, what it is he doing to ease that and the time frame around it. And the reason I'm asking is obviously the prescription trends haven't seen -- haven't shown too much of an inflection yet. And I do understand that the approval only came late last year, but it does suggest that off-label use was maybe a little bit restricted, which I'm assuming is related to those practical challenges, so any color on that would be very helpful.

我將堅持一個，在輔助設置中的 Tagrisso 上，現在你有伴隨列表和批准。我只是想知道 Dave 是否可以談談在將患者從外科醫生轉移到腫瘤科醫生的過程中可能存在的操作挑戰，他正在做什麼來緩解這種挑戰以及圍繞它的時間框架。我問的原因顯然是處方趨勢還沒有看到——還沒有顯示出太多的變化。我知道去年年底才獲得批准，但它確實表明標籤外使用可能受到了一些限制，我假設這與那些實際挑戰有關，所以任何顏色都會非常有幫助.

Dave, do you want to cover this? And you have to remember, Michael, also that even the pandemic is clearly limiting our ability to interact with physicians. And this has a bigger impact on launches than existing established products. Dave, over to you.

戴夫，你想報導這個嗎？邁克爾，你還必須記住，即使是大流行病也明顯限制了我們與醫生互動的能力。這對發布的影響比現有的成熟產品更大。戴夫，交給你了。

Thanks, Pascal. I think, Michael, maybe I'll start with the second part of your question first, which is about the uptake that we might have seen spontaneously prior to approval. I think it's also important to remember we had high-level results just in May of last year. We got to approval in December in the United States. And within that time frame, we also had a publication take place, but NCCN guidelines weren't updated to reflect the ADAURA data until late last year. And so I think that that's different than perhaps what you might be expecting to see in other places where we're working on a longer time line from high-level results and the presentation of those data in between that and approval. So I think that actually, together with the pandemic, as Pascal raises, was part of the aspect of it. I'm really happy to say that the response from physicians in just the 1 month that we have been promoting ADAURA has been very positive. We already have nearly 2/3 of physicians with unaided awareness of the 80% reduction in the risk of recurrence. We are getting very good traction both from surgeons as well as from pathology as well as from medical oncologists. And I think the experiences that we had, with PACIFIC, of working with a multidisciplinary team have really served us well here in terms of engaging with all of the different specialties that are involved in treating in early stage. And I think surgeons are very open and interested to learning more about Tagrisso and ADAURA because it's obviously coming after surgery and not as a substitute or replacement for it.

謝謝，帕斯卡。我想，邁克爾，也許我會先從你問題的第二部分開始，這是關於我們在批准之前可能自發看到的接受情況。我認為同樣重要的是要記住我們在去年 5 月才取得了高水平的成果。我們於 12 月在美國獲得批准。在那段時間範圍內，我們也發表了一篇文章，但 NCCN 指南直到去年年底才更新以反映 ADAURA 數據。因此，我認為這可能與您可能期望在其他地方看到的不同，在其他地方我們正在從高水平結果和在該結果與批准之間的這些數據的呈現中處理更長的時間線。所以我認為，正如帕斯卡提出的那樣，實際上，連同大流行病，是它的一部分。我真的很高興地說，在我們推廣 ADAURA 的短短 1 個月內，醫生們的反應非常積極。我們已經有近 2/3 的醫生獨立意識到復發風險降低了 80%。我們從外科醫生、病理學和腫瘤內科醫生那裡得到了很好的支持。而且我認為我們在 PACIFIC 與多學科團隊合作的經驗在與參與早期治療的所有不同專業方面的合作方面確實對我們很有幫助。而且我認為外科醫生非常開放並且有興趣了解更多關於 Tagrisso 和 ADAURA 的信息，因為它顯然是在手術後出現的，而不是作為它的替代品或替代品。

And we really also are quite pleased that, while it's qualitative, what we're hearing back from physicians is their -- an intention to use across stages. And so whether it's Ib, II or IIIa, we're hearing an intent to use. It's consistent across, which is what we saw in the data. So we do need to continue working on referrals. We need to continue working on driving testing rates, which are only at about 50% in the adjuvant setting. We need to drive use of adjuvant therapy, which is only about 25% today. So the educational barriers are there, but I'm quite pleased with the first month and look forward to continued progress into the year. So that's kind of my outlook.

我們真的也很高興，雖然它是定性的，但我們從醫生那裡聽到的是他們的 - 跨階段使用的意圖。因此，無論是 Ib、II 還是 IIIa，我們都聽到了使用意圖。它是一致的，這就是我們在數據中看到的。因此，我們確實需要繼續進行推薦工作。我們需要繼續努力提高駕駛考試率，在輔助環境中駕駛考試率僅為 50% 左右。我們需要推動輔助治療的使用，目前這一比例僅為 25% 左右。所以教育障礙是存在的，但我對第一個月很滿意，並期待在今年繼續取得進展。這就是我的看法。

Thanks, Dave. Luisa Hector of Berenberg.

謝謝，戴夫。貝倫貝格的路易莎·赫克托。

I'd also like to take the opportunity just to extend our thanks to all your employees for the hard work on the COVID vaccine. So my question is on the 2021 guidance and some of the moving parts. I just want to understand a little bit the range and whether you could contribute -- sorry, specifically comment on ex U.S. synergies and how that may impact in the year. Because I think the rights return to you partway. And do you expect more disposal gains this year, or are you pretty much done? Because you have a high number coming in Q1.

我還想藉此機會感謝您所有的員工為 COVID 疫苗所做的辛勤工作。所以我的問題是關於 2021 年指南和一些變動部分。我只想了解一點範圍以及您是否可以做出貢獻——抱歉，具體評論前美國的協同效應以及它在今年可能產生的影響。因為我認為權利會中途返回給你。你預計今年會有更多的處置收益，還是你已經完成了？因為第一季度會有很多人來。

And Tagrisso China. What proportion of your EM sales are in China? And can you talk a little bit about the impact of the price cut as we go through the quarters? Because I think the price cut hit sooner than you see the volume uplift from the expansion.

還有Tagrisso中國。您的新興市場銷售額中有多少來自中國？在我們經歷這些季度時，您能談談降價的影響嗎？因為我認為降價來得比你看到擴張帶來的銷量提升要早。

Thanks, Luisa. Marc, do you want to cover the guidance questions? And maybe David will address the Tagrisso China question. And again, Luisa, just to remind you, unfortunately, this year we are more limited than usual in terms of how much we can comment, for the reasons we've described before. Over to you, Marc.

謝謝，路易莎。馬克，你想回答指導問題嗎？也許 David 會解決 Tagrisso 中國問題。路易莎，再次提醒你，不幸的是，由於我們之前描述的原因，今年我們在評論方面比往年更加有限。交給你了，馬克。

Yes. So I think I will take the question of the gains from disposals and how much for the year. So what I can say is that other operating income will continue to be a part of our business but will play less overall in the medium term, but I can't comment specifically on the year 2021. You are already aware of what we have announced, obviously. There will be some more, but I can't comment specifically on it. But over the medium term, this, the other income, will continue but play a lower, lesser role.

是的。所以我想我會回答處置收益的問題以及今年的收益。所以我能說的是，其他營業收入將繼續成為我們業務的一部分，但在中期總體上將發揮較小的作用，但我無法具體評論 2021 年。您已經知道我們宣布的內容， 明顯地。還會有更多，但我不能具體評論。但從中期來看，這項收入，即其他收入，將繼續存在，但發揮的作用會越來越小。

And synergies, Marc. Or do you want to...

和協同作用，馬克。或者你想...

Synergies. I mean, yes, we are -- yes. Synergies is going to be -- we're going to recover synergies, and we are preparing ourselves to transition from AbbVie in many countries. It will not have a major impact in terms of profitability in the year 2021 because this will be sort of part of the year, but over time, of course, it's an important area for us.

協同作用。我的意思是，是的，我們是——是的。協同效應將會——我們將恢復協同效應，我們正在準備在許多國家從 AbbVie 過渡。它不會對 2021 年的盈利能力產生重大影響，因為這將是一年中的一部分，但隨著時間的推移，這對我們來說當然是一個重要領域。

Thanks, Marc. David?

謝謝，馬克。大衛？

So Luisa, on the first question. China represents an important part of Emerging Markets sales. We haven't provided the split between China and the rest of Emerging Markets, but I will also say that Emerging Markets without China are also an important part of that number. And we saw within that area really nice demand growth driven by Taiwan, Hong Kong, Russia, Brazil, Korea. On the specific question about China moving forward: Within China, we did see in the fourth quarter impact from the NRDL stock compensation that we needed to realize as we accrue for stock compensation that we're going to need to make as a result of the NRDL and the lowering of price that will take effect in March.

Luisa，關於第一個問題。中國是新興市場銷售的重要組成部分。我們沒有提供中國與其他新興市場之間的差異，但我還要說，不包括中國在內的新興市場也是該數字的重要組成部分。我們在該地區看到了由台灣、香港、俄羅斯、巴西、韓國推動的非常好的需求增長。關於中國前進的具體問題：在中國，我們確實在第四季度看到了我們需要實現的 NRDL 股票補償的影響，因為我們需要獲得股票補償，這是由於醫保和降價將於三月份生效。

As we saw with FLAURA -- or excuse me. As we saw with the second line, as we've also seen in other indications, it does take several quarters -- or excuse me, several months, maybe as many as 2 quarters, for the volume uptake to start to compensate for the pricing. And it really is a function of how quickly we can get up the curve in terms of adoption within front line. I will say that I'm pleased that we have the opportunity to expand access to front-line patients in China. You saw the speed with which we were able to grow the business when we got second-line NRDL listing. And I have every confidence that the team in China is going to be able to do the same with front line; and that the inclusion in the front line on the NRDL, along with the renewal in second line, puts us in a strong spot with Tagrisso where in the front line and in the second line there is an opportunity to make sure that -- if a patient hasn't received Tagrisso, that they will get the opportunity to do so. So I think we're well positioned in a competitive environment there.

正如我們在 FLAURA 中看到的那樣——或者對不起。正如我們在第二行中看到的那樣，正如我們在其他跡像中看到的那樣，確實需要幾個季度——或者對不起，幾個月，可能多達兩個季度，銷量開始補償定價.這實際上取決於我們在前線採用方面能夠以多快的速度上升曲線。我要說的是，我很高興我們有機會擴大對中國一線患者的接觸。當我們獲得二線 NRDL 清單時，您看到了我們發展業務的速度。我完全相信中國的團隊能夠在前線做同樣的事情；納入 NRDL 的前線以及二線的更新，使我們與 Tagrisso 處於強勢地位，在前線和二線，我們有機會確保——如果患者尚未接受 Tagrisso，他們將有機會這樣做。所以我認為我們在競爭激烈的環境中處於有利地位。

Thank you, Dave. Keyur Parekh at Goldman.

謝謝你，戴夫。高盛的 Keyur Parekh。

Can you hear me okay? 2 quick questions, please. The first one, on Enhertu. Dave, from your perspective, as we look at kind of the upcoming data sets in the second line and kind of the low HER2, kind of what is the clinical profile that you would like to go to the market with, especially given how established kind of Kadcyla is in that setting? And then separately, on the SERD, kind of quite a competitive space from what we can see, so just wondering kind of where you see the potential for differentiation on your SERD versus some of the others that are probably slightly ahead of your SERD.

你能聽到我說話嗎？請回答 2 個快速問題。第一個，關於恩赫圖。戴夫，從你的角度來看，當我們看到第二行即將到來的數據集和低 HER2 時，你想進入市場的臨床概況是什麼，特別是考慮到建立的類型Kadcyla 是在那種情況下？然後分別在 SERD 上，從我們所看到的來看，這是一個相當有競爭力的空間，所以只是想知道你在哪裡看到你的 SERD 與其他一些可能略微領先於你的 SERD 的差異化潛力。

Thanks, Keyur. So Dave, maybe you can cover both questions. And Cristian could add anything that he thinks is relevant to add to what you will say. Go ahead, David.

謝謝，基爾。所以戴夫，也許你可以涵蓋這兩個問題。 Cristian 可以添加他認為相關的任何內容以添加到您要說的內容中。去吧，大衛。

Great. Thank you so much. I appreciate that. So I mean I think, in terms of the profile that we're looking for in the head-to-head study, what we know from Kadcyla second-line study, in the EMILIA study, was that they were able to demonstrate a median PFS of 9.6 months, overall response rate of 43%. And that was in patients that had median lines of therapy of 1. We also know that, that study was run at a time before adjuvant Perjeta was really something that was standard of care. And I think that's important to keep in mind, that we're running now in a context of all the Enhertu studies are running in the context of patients who've all been previously treated with standard of care, which is now trastuzumab and pertuzumab. So we certainly think that the control arm, which is Kadcyla, should probably in the real world today be performing at or maybe even a little bit slightly below what you saw in EMILIA. And the results that we saw in third line that are what our breakthrough therapy designation and approval were based upon actually are getting into the 14 months of PFS range and overall response rates of 60%. And so we have every expectation, as we bring that into earlier settings, that, that should improve. So that's kind of how we're taking a look at the outlook on Enhertu. And I think that will be a very compelling profile. Susan -- I mean, Cristian, in terms of the oral SERD and next generation, do you want to comment on some of the aspects of how we think about differentiation?

偉大的。太感謝了。我很感激。所以我的意思是，我認為，就我們在頭對頭研究中尋找的概況而言，我們從 EMILIA 研究中的 Kadcyla 二線研究中了解到，他們能夠證明中位數PFS 為 9.6 個月，總緩解率為 43%。那是在中位治療線為 1 的患者中進行的。我們還知道，該研究是在輔助 Perjeta 真正成為標準治療之前進行的。我認為記住這一點很重要，我們現在在所有 Enhertu 研究的背景下進行，這些患者之前都接受過標準治療，現在是曲妥珠單抗和帕妥珠單抗。所以我們當然認為，控制臂，也就是 Kadcyla，在今天的現實世界中應該可以達到甚至略低於你在 EMILIA 中看到的水平。我們在三線中看到的結果是我們的突破性療法指定和批准所基於的結果實際上正在進入 14 個月的 PFS 範圍和 60% 的總體反應率。因此，當我們將其帶入早期設置時，我們滿懷期望，這應該會有所改善。這就是我們看待 Enhertu 前景的方式。我認為這將是一個非常引人注目的形象。蘇珊——我的意思是，克里斯蒂安，就口頭 SERD 和下一代而言，你想評論一下我們如何看待差異化的某些方面嗎？

Sure, sure, Dave. Thank you. And thank you for the question. And we presented the data from SERENA-1, our Phase I trial with camizestrant, our oral SERD. And we believe that this drug has a best-in-class potential in terms of providing superior clinical benefit at well-tolerated dose. You have seen the 75-milligram QD. That is the dose that we are moving in registrational trials. The results showed a median PFS of more than 11 months and a clinical benefit rate exceeding 50%, with no dose reduction, discontinuation, no GI toxicity. This drug is already in 2 Phase II trials, SERENA-2 that is comparing camizestrant versus fulvestrant in patient with metastatic breast cancer and SERENA-3 that is a window-of-opportunity trial. There are several exciting combinations that we are entering now in Phase III pivotal trials. We've just started the first-line combination trial with palbociclib. So we are -- we have a very strong and robust clinical development plan with these drugs.

當然，當然，戴夫。謝謝你。謝謝你的問題。我們展示了 SERENA-1 的數據，這是我們使用 camistrant 進行的 I 期試驗，我們的口服 SERD。我們相信，這種藥物在以良好耐受劑量提供卓越的臨床益處方面具有同類最佳的潛力。您已經看到了 75 毫克 QD。這就是我們在註冊試驗中使用的劑量。結果顯示中位 PFS 超過 11 個月，臨床獲益率超過 50%，沒有減量、停藥，沒有 GI 毒性。該藥物已經在進行 2 項 II 期試驗，SERENA-2 比較轉移性乳腺癌患者的卡米司群與氟維司群，SERENA-3 是一項機會窗口試驗。我們現在正在進入 III 期關鍵試驗的幾個令人興奮的組合。我們剛剛開始了與 palbociclib 的一線組合試驗。所以我們 - 我們對這些藥物有一個非常強大和穩健的臨床開發計劃。

Thanks, Cristian. We -- I mean maybe we could stay on the SERD. There is a question from Steve Scala of Cowen. And Steve's question is: "Sanofi says it has a best-in-class molecule. What data would you point to that might argue otherwise?" So we typically don't comment on competitors' products, but maybe you could again sort of comment on what makes our products so different.

謝謝，克里斯蒂安。我們——我的意思是也許我們可以留在 SERD。 Cowen 的 Steve Scala 提出了一個問題。史蒂夫的問題是：“賽諾菲說它擁有一流的分子。你會指出哪些數據可能會反駁？”因此，我們通常不會對競爭對手的產品發表評論，但也許您可以再次對是什麼讓我們的產品如此與眾不同發表評論。

I think that what I just mentioned in terms of level of efficacy as a monotherapy in a very heavily pretreated patient population, pretreated with CDK4/6 inhibitor, pretreated with chemotherapy, showing this level of progression-free survival and especially disease control rate, is quite compelling with our molecule. In addition, our safety profile, especially at the dose that we selected to move into pivotal trials, show a very benign tolerability. We almost -- we do not have dose reduction. We don't have discontinuations for adverse event at 75 mg; and compared maybe other molecule, the GI toxicities, the hot flashes. So those adverse event that sometimes [represent adverse-some for patients] seems to be quite good. So we have a good molecule and we are developing it in a very accelerated way.

我認為我剛才提到的作為單一療法的療效水平在經過大量預處理的患者人群中，用 CDK4/6 抑製劑預處理，用化學療法預處理，顯示出這種水平的無進展生存率，尤其是疾病控制率，是我們的分子非常引人注目。此外，我們的安全性概況，尤其是在我們選擇進入關鍵試驗的劑量下，顯示出非常良好的耐受性。我們幾乎 - 我們沒有減少劑量。我們沒有因 75 mg 的不良事件而停藥；並與其他分子、胃腸道毒性、潮熱進行比較。所以那些有時[代表對患者不利的一些]的不良事件似乎是相當好的。所以我們有一個很好的分子，我們正在以非常快的方式開發它。

Thanks, Cristian. So still Oncology, another question from Steve, about Imfinzi. And it's a question for you, Leon, I think. And Dave, maybe you can also comment, but -- so Leon, the question is, are you seeing off-label use of competitors in China for the PACIFIC regimen?

謝謝，克里斯蒂安。 Steve 提出的另一個關於 Imfinzi 的問題仍然是腫瘤學。我想這是問你的問題，Leon。戴夫，也許你也可以發表評論，但是——萊昂，問題是，你是否看到中國的競爭對手在 PACIFIC 養生法中超適應症使用？

Yes. I think we are seeing quite a lot off-label usage of competitors in China, using off label, but the PACIFIC regimen, Stage III lung cancer in China, the market is at the moment quite underdeveloped. We see some, but still we are able to defend the large share for this PACIFIC regimen with Imfinzi. And our Imfinzi also have some spontaneous usage of small cell lung cancer. So I think ultimately we -- Imfinzi, with the good data, we should be owning the space of the Stage III even at a self-pay situation.

是的。我認為我們在中國看到了相當多的競爭對手的標籤外使用，使用標籤外，但 PACIFIC 方案，中國的 III 期肺癌，目前市場還很不發達。我們看到了一些，但我們仍然能夠與 Imfinzi 一起捍衛這個 PACIFIC 養生法的大部分份額。而我們Imfinzi也有一些小細胞肺癌的自髮用法。所以我認為最終我們 - Imfinzi，憑藉良好的數據，即使在自費情況下，我們也應該擁有第三階段的空間。

Thank you, Leon. The next question is from...

謝謝你，萊昂。下一個問題來自...

I mean I think, on the whole, Pascal...

我的意思是，我認為，總的來說，Pascal...

Sorry, Dave. Yes, go ahead, Dave...

對不起，戴夫。是的，繼續，戴夫...

No, no, just to add onto what Leon was saying. I mean I think that -- for clarity on this. So the off-label use of checkpoint inhibitors is something that, as Leon pointed out, he's seeing, we're seeing within China. The reason that the Stage III is less well developed is because obviously that requires chemoradiotherapy, multidisciplinary teams. And I think that the work that Leon and his team are doing to develop that marketplace really is putting us in the right position to be able to defend the on-label use for PACIFIC. And so there's certainly a lot of off-label competition throughout checkpoint inhibitors, but I think that Leon is [clued in on a] key piece, which is that we're playing a role in the development of that way of treating patients which doesn't exist. And that's something that we've really developed a skill set on in China. Thanks.

不，不，只是為了補充 Leon 所說的話。我的意思是，我認為——為了清楚起見。因此，正如 Leon 指出的那樣，檢查點抑製劑的標籤外使用是他正在看到的，我們正在中國看到。第三階段發展不太好的原因是因為這顯然需要放化療、多學科團隊。我認為 Leon 和他的團隊為開發該市場所做的工作確實使我們處於正確的位置，能夠捍衛 PACIFIC 的標籤上使用。因此，在整個檢查點抑製劑中肯定存在很多標籤外競爭，但我認為 Leon 是 [線索] 關鍵部分，即我們在開發治療患者的方法中發揮作用'存在。這就是我們在中國真正培養出的一套技能。謝謝。

Thanks, David. Next question is from Andrew Baum of Citi.

謝謝，大衛。下一個問題來自花旗銀行的安德魯鮑姆。

Question for Ruud and then one for Mene. So for Ruud: It appears to me that -- the anticipated timing of generic entry into the U.S., since we pushed out into the second half of '28, I just noticed the patent term extension you got. I just wanted to confirm that's correct or whether it's still the '25 that you've previously outlined. And then also any comments on how long COVID may result in Farxiga demand due to either increased renal or heart failure?

問題給 Ruud，然後一個給 Mene。所以對於 Ruud 來說：在我看來——仿製藥進入美國的預期時間，因為我們推出了 28 年下半年，我剛剛注意到你得到的專利期限延長。我只是想確認這是正確的，或者它是否仍然是您之前概述的 25 年。然後還有關於 COVID 可能由於腎臟或心力衰竭增加而導致 Farxiga 需求多長時間的任何評論？

And then for Mene. On the subject assuming we will require novel vaccines to address these -- some of these variants or emerging variants, how relaxed should we be about the challenges of developing novel vaccines, be it multivalents or otherwise? I'm thinking both from an efficacy point of view, things like antigenic sin, anti-vector antibodies, as well as from a safety point of view.

然後是梅內。關於假設我們需要新疫苗來解決這些問題——其中一些變體或新出現的變體，我們應該對開發新疫苗的挑戰有多放鬆，無論是多價疫苗還是其他疫苗？我既從功效的角度考慮，如抗原原罪、抗載體抗體，又從安全的角度考慮。

Okay, Andrew...

好的，安德魯...

[Thanks, Andrew. So Ruud], will you take the first questions? And Mene will cover the vaccines.

[謝謝，安德魯。那麼 Ruud]，你會回答第一個問題嗎？梅內將負責疫苗。

Yes, absolutely, Pascal. So on your first question, Andrew, based on my latest information, it's still 2025. The only piece is that we're also going to apply for a pediatric extension, so that will give potentially a 6 months extension of our patents. So moving in the United States into 2026.

是的，絕對是，帕斯卡。所以關於你的第一個問題，安德魯，根據我的最新信息，它仍然是 2025 年。唯一的一點是我們還將申請兒科延期，因此我們的專利可能會延長 6 個月。因此，在美國進入 2026 年。

Regarding COVID-19 impact on Farxiga and the outlook on heart failure and kidney disease patients. We are very bullish, Andrew. Yes, there is an issue. Our field forces are doing their best to reach out to nephrologists as well as to cardiologists. And it's going well, if you see the data, but equally, of course, there is an COVID-19 impact. I'm not going to play it down, but overall if you look at the performance of Farxiga also in the last quarter across all regions, a 40% growth. It clearly shows the enormous potential of this product portfolio. And we are very excited, as Pascal already mentioned in his opening statements, that we were granted priority review for CKD in the United States as well as in Japan. So yes, there is a little bit of headwind regarding COVID, but equally the teams are doing a phenomenal job in order to drive this product where it needs to be. Mene?

關於 COVID-19 對 Farxiga 的影響以及對心力衰竭和腎病患者的展望。我們非常樂觀，安德魯。是的，有一個問題。我們的現場工作人員正在盡最大努力接觸腎髒病學家和心髒病學家。如果你看到數據，它進展順利，但同樣，當然，也有 COVID-19 的影響。我不會淡化它，但總的來說，如果你看看 Farxiga 在上個季度在所有地區的表現，增長了 40%。它清楚地顯示了該產品組合的巨大潛力。我們非常興奮，正如 Pascal 在他的開場白中提到的那樣，我們在美國和日本獲得了 CKD 的優先審查。所以，是的，關於 COVID 有一些不利因素，但同樣，為了將這個產品推向需要的地方，團隊正在做非凡的工作。梅內？

Thank you. There is a lot of questions there, Andrew, so I'm going to try and answer as many as I can. So first of all, your first point is if we need new vaccines. I think the jury is still out. I think, with regards to protecting, even with these new variants, against severe disease hospitalizations, it may well be that the current crop of vaccines we have are going to be good enough, but if we do end up needing new variants, then I think we're all going to be able to move reasonably quickly. We've started to work on new variant vaccines based on the new sequences sometime ago. And we're hoping to be in the clinic in the springtime, ready for being able to put it into people's arms in the autumn time frame. So a few weeks behind the [mRNAs] but not that far behind. In terms of antigenic sin, whether you're going to have multivariant vaccines in a single dose or dose sequentially, those are all questions we don't understand. So I think right now people are assuming that -- if you dose with a next-gen variant as a boost, that you will drive the immune response to be able to give you protection against the new variants. That's not necessarily true because you may have already biased the immune response to the original variant. So we're going to have to do those experiments, Andrew, and actually work that out using immunogenicity and neutralization assays, but I think those are all the things that we will be working out over the coming weeks and months.

謝謝你。安德魯，那裡有很多問題，所以我會盡可能多地回答。所以首先，你的第一點是我們是否需要新疫苗。我認為陪審團還沒有定論。我認為，關於保護，即使有這些新變種，也可以防止嚴重疾病住院，我們目前擁有的疫苗很可能已經足夠好了，但如果我們最終確實需要新變種，那麼我認為我們都將能夠合理快速地採取行動。我們已經開始研究基於新序列的新變異疫苗。我們希望在春季進入診所，準備好在秋季將其投入人們的懷抱。所以比 [mRNAs] 晚了幾週，但並沒有落後那麼多。就抗原原罪而言，無論是單劑還是序貫接種多變體疫苗，這些都是我們不了解的問題。所以我認為現在人們假設——如果你使用下一代變體作為增強劑，你將推動免疫反應，從而能夠保護你免受新變體的侵害。這不一定是正確的，因為您可能已經使免疫反應偏向於原始變體。所以我們將不得不做這些實驗，安德魯，並使用免疫原性和中和分析來實際解決這個問題，但我認為這些都是我們將在未來幾周和幾個月內解決的問題。

Thanks, Mene. The next question is from Sachin at Bank of America.

謝謝，梅內。下一個問題來自美國銀行的 Sachin。

Sachin Jain here, Bank of America. I have 2 topics, if I may. Firstly, on tezepelumab, I wondered if you can just discuss the relevance of the source data which didn't show a benefit on steroid reduction. I'm a bit confused that powering seems to be cited as a reason given the study size isn't that different to the Dupixent (inaudible) studies. And if you could just touch on commercial relevance of having missed that study.

Sachin Jain 在這裡，美國銀行。如果可以的話，我有 2 個主題。首先，關於 tezepelumab，我想知道您是否可以討論未顯示對類固醇減少有益的源數據的相關性。我有點困惑，考慮到研究規模與 Dupixent（聽不清）研究沒有太大不同，供電似乎被引用為一個原因。如果你能談談錯過那項研究的商業相關性。

And the second one is just back to cash flow, for Marc. I wonder if you could comment to what sort of free cash flow improvement we should see in '21 relative to consensus at around $6.5 billion, $7 billion on operating cash flow. And then related: You've been fairly vocal on dividend increases as part of the Alexion acquisition. When do you expect you can get more concrete on that in terms of payout ratio as a combined free cash flow? And your intent to specifically target income investors given the dynamics elsewhere in the sector.

對馬克來說，第二個只是回歸現金流。我想知道你是否可以評論我們在 21 年應該看到什麼樣的自由現金流改善，相對於共識，大約 65 億美元，運營現金流為 70 億美元。然後是相關的：作為 Alexion 收購的一部分，你一直非常直言不諱地增加股息。您預計什麼時候可以更具體地了解派息率作為綜合自由現金流的情況？鑑於該行業其他地方的動態，您打算專門針對收入投資者。

Thanks, Sachin. Can I suggest that, Mene, you cover first the source data and the interpretation? And then Ruud can cover the commercial relevance, and Marc the financial questions.

謝謝，薩欽。 Mene，我可以建議你先介紹源數據和解釋嗎？然後 Ruud 可以討論商業相關性，而 Marc 可以討論財務問題。

Yes. Thanks, Sachin. So first of all, it's not a powering of the study that led to the [negatives]. So I think it's the design of the study and some of the nuances within that. And I think, when we present it, it will become clearer. I don't think it impacts the filing for teze in any way. And actually the data were very consistent with what we saw with tezepelumab. It's really the placebo arms [in performers we wished when you see the data]. We still feel confident teze will indeed provide steroid sparing or reduction over time. And we'll need to read -- run another study to prove that, but there's nothing about the powering of the study that's led to this result. Ruud?

是的。謝謝，薩欽。所以首先，導致[負面影響]的不是研究的力量。所以我認為這是研究的設計以及其中的一些細微差別。而且我認為，當我們展示它時，它會變得更加清晰。我認為這不會以任何方式影響 teze 的申請。實際上，這些數據與我們在 tezepelumab 上看到的非常一致。這真的是安慰劑組 [當你看到數據時我們希望的表演者]。我們仍然相信 teze 確實會隨著時間的推移提供類固醇的保留或減少。我們需要閱讀 - 進行另一項研究來證明這一點，但沒有任何關於導致這一結果的研究的動力。魯德？

Yes. Thank you, Mene. From a commercial perspective, Sachin, we are, I think, together with our colleagues of Amgen, very excited about this product irrespective of the source data. And I think it's the first time that biologic is clearly showing a very strong effect in low eosinophils. None of the other biologicals have been able to show that. So the potential is very substantial. Roughly 60% are in what is called the moderate- to low-eosinophil situation. So in that sense I think it will be an extremely good product in order to serve those patients, but equally I agree with Mene. We will do more analysis and we will look whether it makes sense in order to do another study, but in the short term I don't expect any major impacts based on the source data.

是的。謝謝你，梅內。從商業角度來看，Sachin，我認為我們和我們安進的同事一起，無論源數據如何，都對這個產品感到非常興奮。我認為這是第一次生物製劑在低嗜酸性粒細胞中明顯顯示出非常強的作用。其他生物製品都無法證明這一點。所以潛力是非常可觀的。大約 60% 處於所謂的中等至低嗜酸性粒細胞情況。所以從這個意義上說，我認為這將是一個非常好的產品，可以為那些患者服務，但我同樣同意 Mene 的觀點。我們會做更多的分析，我們會看看它是否有意義，以便進行另一項研究，但在短期內，我預計不會根據源數據產生任何重大影響。

Marc?

馬克？

So yes. So on the cash flow, I'm not going to be able to give you a guidance on the cash flow for 2021, but I think I would like to explain that the sort of benefit that we got on the cash flow in 2020 due to the vaccine will obviously reverse itself in part in 2021. So this needs to be considered. If we just look at the sort of underlying cash flow, I think you will have a similar trend as the one we saw over 2020 versus '19, which is a faster growth of the underlying cash flow if we exclude the vaccine. So I think you need to take these 2 elements in consideration. If we talk about the dividend: So what we have said is, with the Alexion or if we do acquire Alexion, we'll have a stronger capacity for dividend expansion. We haven't provided any specific timing, but we have answered the question in the past of whether this would take place in 2021. And we have answered that 2021 will be a very busy year for us, and therefore post 2021 seems to be a better time to increase the dividend, but we haven't provided the sort of the fixed payout ratio going forward but clearly a stronger capacity to expand the dividend from 2022.

所以是的。因此，關於現金流，我無法為您提供 2021 年現金流的指導，但我想我想解釋一下，我們在 2020 年的現金流中獲得的收益是由於疫苗顯然會在 2021 年部分逆轉。因此需要考慮這一點。如果我們只看潛在現金流的類型，我認為你會看到與我們在 2020 年看到的趨勢與 19 年類似的趨勢，如果我們排除疫苗，則潛在現金流的增長更快。所以我認為你需要考慮這兩個因素。如果我們談論股息：所以我們所說的是，有了亞力兄，或者如果我們確實收購了亞力兄，我們將有更強的股息擴張能力。我們沒有提供任何具體時間，但我們已經回答了過去是否會在 2021 年發生的問題。我們已經回答說 2021 年對我們來說將是非常忙碌的一年，因此 2021 年後似乎是增加股息的更好時機，但我們沒有提供未來的固定派息率，但顯然有更強的能力從 2022 年開始擴大股息。

Thanks, Marc. Tim Anderson at Wolfe Research.

謝謝，馬克。 Wolfe Research 的蒂姆·安德森 (Tim Anderson)。

I have a question on Enhertu and specifically on DESTINY-Breast04 in the HER2 low segment. To me, of the various readouts occurring in 2021, that's perhaps the most exciting. It's a large segment of the market. It's one that's untapped with current HER2 therapies, so it's quite novel. I'm hoping you can characterize the riskiness of this particular trial and also the commercial meaningfulness of that particular trial relative to the other readouts. And then on Farxiga, in the DELIVER results in the HFpEF heart failure segment, it could be quite meaningful, but it's hard for me to handicap the risk of that, so what's your confidence in a positive readout on that trial later in the year?

我有一個關於 Enhertu 的問題，特別是關於 HER2 低段中的 DESTINY-Breast04。對我來說，在 2021 年發生的各種讀數中，這可能是最令人興奮的。這是一個很大的市場部分。這是目前 HER2 療法尚未開發的一種療法，因此非常新穎。我希望你能描述這個特定試驗的風險以及該特定試驗相對於其他讀數的商業意義。然後在 Farxiga 上，在 HFpEF 心力衰竭部分的 DELIVER 結果中，它可能非常有意義，但我很難阻止這種風險，那麼你對今年晚些時候對該試驗的積極讀數有何信心？

Thanks, Tim. So Cristian, can you cover the first one? And Dave could add to this. And Mene, if you could cover the second question but relatively quickly because we still have a lot of questions and we would like to give everybody a chance.

謝謝，蒂姆。那麼克里斯蒂安，你能報導第一個嗎？戴夫可以補充這一點。 Mene，請問你能否回答第二個問題，但速度相對較快，因為我們還有很多問題，我們希望給每個人一個機會。

Sure. Thank you for the question. The DB04 trial, I'm very much in agreement with you, is a very exciting trial, one of the most important readouts that we will have the second half of this year. And it's a study that is currently comparing in 540 patients Enhertu versus chemo standard of care. The chemo standard of care is a choice between different cytotoxic: capecitabine, gemcitabine, paclitaxel, nab-paclitaxel and eribulin. This is a trial that we are running in pretreated patients. It is a trial that is based on the preliminary data that we have been reported in HER2-low breast cancer in a later-line treatment [in] probably every [pretreated, more] heterogeneous patient population. I think the data that we have presented give us confidence that Enhertu in this segment can be definitely superior to monotherapy, the monotherapy that I just mentioned. So -- and this is a very important trial because, based on the results of this trial, we will decide what's next in this specific segment, HER2 low. And of course, this can give us opportunity to expand further this segment with combinations or even going earlier in terms of line of therapy.

當然。感謝你的提問。 DB04 試驗，我非常同意你的看法，是一個非常令人興奮的試驗，是我們將在今年下半年獲得的最重要的讀數之一。這是一項目前在 540 名患者中比較 Enhertu 與化療標準護理的研究。化療護理標準是在不同的細胞毒性藥物之間進行選擇：卡培他濱、吉西他濱、紫杉醇、nab-紫杉醇和艾日布林。這是我們在接受過治療的患者中進行的一項試驗。這是一項基於初步數據的試驗，我們在 HER2-low 乳腺癌的後線治療中報告了這些初步數據 [in] 可能是每個 [pretreated, more] 異質性患者群體。我認為我們提供的數據讓我們有信心，Enhertu 在這一領域絕對優於單一療法，即我剛才提到的單一療法。所以——這是一個非常重要的試驗，因為根據這個試驗的結果，我們將決定這個特定部分的下一步，HER2 low。當然，這可以讓我們有機會通過組合進一步擴大這一細分市場，甚至在治療線方面走得更早。

Dave, anything you want to say very quickly?

戴夫，你有什麼想很快說的嗎？

Yes. So very quickly, Tim, what I would say is that commercially it could be very attractive. It will obviously depend upon the data. HER2 low could be as big as 3x the size of HER2 positive, but remember HER2 low is a continuous variable. It's not a binary one. And so we'll have to see kind of what the data show when the data come out, but in terms of opportunity, we're certainly excited about it.

是的。所以很快，蒂姆，我想說的是，在商業上它可能非常有吸引力。這顯然取決於數據。 HER2 low 可能是 HER2 陽性大小的 3 倍，但請記住 HER2 low 是一個連續變量。它不是二進制的。因此，當數據出來時，我們必須看看數據顯示的內容，但就機會而言，我們當然對此感到興奮。

Thanks. Mene, HFpEF?

謝謝。梅內，HFpEF？

Yes. I mean I'm not going to give a probability of success. I would say HFpEF is definitely more challenging, but I think, with what we've seen so far across our studies, we feel confident that we should get a -- hopefully, a positive readout, but ultimately the trial will read out and we'll see the results when we get them this year for HFpEF.

是的。我的意思是我不會給出成功的可能性。我會說 HFpEF 肯定更具挑戰性，但我認為，根據我們迄今為止在研究中所看到的情況，我們有信心我們應該得到一個——希望是一個積極的讀數，但最終試驗會讀出，我們當我們今年獲得 HFpEF 的結果時就會看到結果。

Okay. Thanks, Mene. Since we are on Farxiga: There is a question from Sam Fazeli at Bloomberg about Farxiga consensus estimates for Ruud. Do you think they are sufficiently reflecting the potential for the drug? And can you update on the potential for patent protection in the long term, Ruud?

好的。謝謝，梅內。由於我們在 Farxiga 上：彭博社的 Sam Fazeli 提出了一個關於 Farxiga 對 Ruud 的共識估計的問題。您認為它們是否充分反映了該藥物的潛力？ Ruud，從長遠來看，您能否更新專利保護的潛力？

Yes. So Pascal -- and thanks for the question, Sam. We're not commenting too much about the absolute numbers. The only thing I can say is that we are very pleased with the very strong performance across all the geographies, that the potential, of course, of CKD is very, very substantial. It requires a lot of market development, but we are working hard on that. And equally, of course, in many geographies we have just launched heart failure. And the attractiveness of heart failure is evident and is also now seen by international guidelines and local guidelines. So once again, I'm not going to answer your question, but you can, hopefully, hear my enthusiasm about the potential of Farxiga in the next 6, 7 years. The potential for patent protection: I think -- once again, I think there is a potential in order to extend our patent based on the pediatric indication if that will be granted. So we are working hard on that piece. And then on top of that, we are doing, and Mene was mentioning that, quite extensive combination studies with a couple of other assets, which we will need to wait and to see the results in the next few years.

是的。 Pascal，謝謝你提出這個問題，Sam。我們不會過多評論絕對數字。我唯一能說的是，我們對所有地區的強勁表現感到非常滿意，當然 CKD 的潛力非常非常大。這需要大量的市場開發，但我們正在為此努力。同樣，當然，在許多地區，我們剛剛推出了心力衰竭。而心力衰竭的吸引力是顯而易見的，現在也被國際指南和地方指南所看到。所以再一次，我不會回答你的問題，但希望你能聽到我對 Farxiga 在未來 6、7 年的潛力的熱情。專利保護的潛力：我認為 - 再一次，我認為有可能根據兒科適應症擴展我們的專利，如果獲得批准的話。所以我們正在努力解決這個問題。然後最重要的是，我們正在做，Mene 提到，與其他一些資產進行相當廣泛的組合研究，我們需要等待並在未來幾年內看到結果。

Thanks, Ruud. And Sam had a question about the vaccine. At what point would we consider making a profit? And we still have to define this. And we can in almost all geographies. [And so we] book the sales and keep the profit to ourselves. Alternatively, we share with our partners in the various geographies. The next question is Jo Walton Crédit Suisse.

謝謝，魯德。山姆對疫苗有疑問。在什麼時候我們會考慮盈利？我們仍然需要定義它。我們幾乎可以在所有地區開展業務。 [因此我們] 預訂銷售額並將利潤留給自己。或者，我們與不同地區的合作夥伴共享。下一個問題是 Jo Walton Crédit Suisse。

I'll respect the one-question rule to allow as many people as possible on the call. If we look at your -- if we look at the consensus for 2021, it's just over $5. And that's at the top end of your range. However, there only appears to be about $975 million of other operating income within that. Now you've got some base business of other operating income. You've got the AbbVie income. You've announced the Crestor deal. And you've got the stake, the Viela stake. So presumably, as people put all of those numbers in, that other operating income comes in -- comes up quite significantly. That would normally drive profit, so you would perhaps expect more than $5 of earnings. So I think what people will have to do is increase their level of investment if they're going to keep their earnings still in that $5 range, so my question is, which is the area where we should consider more investment? Is it all discretionary fantastic R&D and you can spend more on R&D? Or is some of the incremental investment that collectively we haven't got in our numbers, and SG&A investment, it's actually going to take more boot on the ground in order to sell these products? And the reason that I ask is partly because the one area that did increase in expense in 4Q was SG&A, up 6% in constant currency, which is a quarter which presumably had some COVID disruption in it. So I'm really trying to get some idea of how that SG&A is going to move going forward.

我會遵守一個問題的規則，允許盡可能多的人接聽電話。如果我們看看你——如果我們看看 2021 年的共識，它剛剛超過 5 美元。那是您範圍的頂端。然而，其中似乎只有約 9.75 億美元的其他營業收入。現在你有一些其他營業收入的基礎業務。你有艾伯維的收入。你已經宣布了 Crestor 交易。你已經拿到了股份，Viela 的股份。所以可以推測，當人們把所有這些數字都放進去時，其他營業收入就會出現——出現相當大的增長。這通常會帶來利潤，因此您可能會期望獲得超過 5 美元的收益。所以我認為，如果人們要將收入保持在 5 美元的範圍內，他們就必須增加投資水平，所以我的問題是，我們應該考慮在哪個領域進行更多投資？是否所有可自由支配的出色研發，您可以在研發上投入更多？或者是我們的數字中沒有的一些增量投資，以及 SG&A 投資，實際上需要更多的啟動才能銷售這些產品？我問的部分原因是，第四季度支出確實增加的一個領域是 SG&A，按固定匯率計算增長了 6%，這個季度可能有一些 COVID 中斷。所以我真的很想了解 SG&A 將如何向前發展。

Thanks, Jo. Marc, it's for you.

謝謝，喬。馬克，這是給你的。

Yes. So thank you, Jo, for the question. So your -- I think your basically triangulation of the other income is -- looks plausible and possible to me. As far the -- you are trying to find one cause of potential differences between us and consensus. First of all, we are -- I think we are very close to consensus, but I think you need to look at probably the integrality of the P&L and starting from gross margin as well as R&D, including SG&A. I think -- yes, I don't think it's only on one line that there's a difference. There is obviously the difference that you mentioned on -- possible difference that you mentioned on other income. I would look at the totality of the lines. And I do apologize, but I can't give you much more indication on each of these lines today, but I would not think it's on one line. I would think that it's maybe a composite on many lines.

是的。喬，謝謝你提出這個問題。所以你 - 我認為你對其他收入的基本三角測量是 - 對我來說看起來合理且可能。就目前而言——您正試圖找出我們與共識之間存在潛在差異的原因之一。首先，我們 - 我認為我們非常接近達成共識，但我認為你可能需要看看 P&L 的完整性，從毛利率和研發開始，包括 SG&A。我認為 - 是的，我不認為只有一條線存在差異。顯然存在您提到的差異 - 您提到的其他收入可能存在差異。我會看看所有的線條。我很抱歉，但我今天不能在每一行上給你更多的指示，但我不認為它在一條線上。我認為它可能是許多方面的綜合。

Thanks, Marc. And sorry. We are speaking in riddles today, Jo, but again as we said, our ability to comment on 2021 is more limited than usual. James Gordon, JPMorgan.

謝謝，馬克。對不起。喬，我們今天說的是謎語，但正如我們所說，我們對 2021 年發表評論的能力比平時更有限。詹姆斯戈登，摩根大通。

Gordon, JPMorgan. One following up on tezepelumab. So we saw the NAVIGATOR data at AAAAI, and the efficacy looked pretty competitive in the high- and the low-eosinophil patients. So is the plan just to go for the lows? That's where you're going to differentiate it? Or are you going to be competing against Fasenra in the highs as well, assuming you get approved in both? And is dose frequency important in this category? I mean GSK were talking about doing long-acting Nucala. Are you going to look to do a long-acting version of either of these products, or is that not really something that [matters] in this space?

戈登，摩根大通。一個跟進 tezepelumab。所以我們在 AAAAI 上看到了 NAVIGATOR 的數據，在高嗜酸性粒細胞和低嗜酸性粒細胞患者中的療效看起來相當有競爭力。那麼這個計劃只是為了低谷嗎？這就是你要區分它的地方？或者你是否也打算在高位與 Fasenra 競爭，假設你在兩個方面都獲得批准？在這個類別中劑量頻率重要嗎？我的意思是 GSK 正在談論做長效 Nucala。您是否打算為這些產品中的任何一種做長效版本，或者這在這個領域真的不是[重要的]？

Secondly, Farxiga. So your comments about the genericization [of the day 20s]. And I can see a few different combo approaches that you're doing for kidney disease which would be a way of extending the IP, but I can't see anything listed at the moment for the combo approach for heart failure. So is there a plan to do combo approaches for heart failure? Or is that bit going to genericize? And then finally, just a clarification on the COVID antibody: I think Mene made some comments about efficacy for COVID-19 variants. Was that talking about the U.K. strain or also talking about being confident in efficacy for the South African strain as well?

其次，法西加。所以你對通用化的評論 [20 年代]。我可以看到你正在為腎臟疾病做的幾種不同的組合方法，這將是擴展 IP 的一種方式，但我目前看不到任何列出的用於治療心力衰竭的組合方法。那麼是否有針對心力衰竭進行聯合治療的計劃？還是那一點要通用化？最後，只是對 COVID 抗體的澄清：我認為 Mene 對 COVID-19 變體的功效發表了一些評論。那是在談論英國毒株還是在談論對南非毒株的療效有信心？

So you're pushing your luck, James, 3 questions in 1. Maybe the first 2, Ruud, you could cover. And then Mene, you could say a couple of words on the long-acting antibody.

所以你是在碰碰運氣，James，1 個問題中有 3 個問題。也許第一個 2 個問題，Ruud，你可以回答。然後 Mene，你可以就長效抗體說兩句。

Yes, of course, Pascal. And thanks, James. Regarding tezepelumab and the positioning, clearly we see this potentially as a best-in-class molecule, and therefore we will not make a distinction between high eosinophils and low eosinophils. We are working here with our partner Amgen, so we are not going to niche ourselves. We will position the product based on in-depth market research. And if that means that we also are going to penetrate in the high eosinophils, we will certainly do that. Regarding your question about how important is dosing: I think it's [important]. It's the less frequent a patient needs to go to a hospital or a clinic or ideally can inject themselves is a win, but equally, of course, this is a class heavily directed by efficacy. And therefore, we have seen multiple times that for the patients most importantly is strong efficacy and less dosing, but equally, of course, if you have a dosing advantage, you will use it.

是的，當然，帕斯卡。謝謝，詹姆斯。關於 tezepelumab 和定位，我們顯然將其視為同類最佳分子，因此我們不會區分高嗜酸性粒細胞和低嗜酸性粒細胞。我們在這裡與我們的合作夥伴 Amgen 合作，因此我們不會將自己定位為利基市場。我們將根據深入的市場調查來定位產品。如果這意味著我們也將滲透到高嗜酸性粒細胞中，我們肯定會這樣做。關於您關於劑量有多重要的問題：我認為它 [重要]。患者需要去醫院或診所的頻率越低，或者理想情況下可以自己注射是一個勝利，但同樣，當然，這是一門以療效為導向的課程。因此，我們多次看到，對於患者來說，最重要的是療效好，劑量少，但同樣，當然，如果你有劑量優勢，你就會使用它。

Farxiga. Question is about heart failure and a combination. Yes, there are multiple combinations in kidney disease, but equally we are also looking at combinations in heart failure. They are a little bit earlier, but where it is possible, we will certainly do that. And when the time is there, we will clearly disclose that.

法西加。問題是關於心力衰竭和組合。是的，腎臟疾病有多種組合，但同樣我們也在研究心力衰竭的組合。他們有點早，但在可能的情況下，我們一定會這樣做。到時候，我們會清楚地披露這一點。

Thanks, Ruud. Mene?

謝謝，魯德。梅內？

And just to add. We already have a dosing advantage (inaudible) 2 months, so well, it is something we're looking at to see if there's any additional benefit of increasing the dosing schedule. With regards to the antibodies, it's against all variants actually. And there's 2 independent laboratories now that have shown that our cocktail -- both antibodies in our cocktail actually are still very potent in neutralizing all of the new variants, [whether it be] South Africa or Kent. And that's in contrast to many of our competitor antibodies where either one or both of the antibodies are actually quite severely [impacted]. So we've -- we're in good shape with our antibody cocktail both for South Africa and Kent variants.

並補充一下。我們已經有 2 個月的劑量優勢（聽不清），所以我們正在研究增加劑量計劃是否有任何額外的好處。關於抗體，它實際上是針對所有變體的。現在有 2 個獨立實驗室已經證明我們的雞尾酒——我們雞尾酒中的兩種抗體實際上仍然非常有效地中和所有新變種，[無論是]南非還是肯特。這與我們的許多競爭抗體形成鮮明對比，其中一種或兩種抗體實際上受到相當嚴重的[影響]。所以我們 - 我們的抗體雞尾酒在南非和肯特變種方面都處於良好狀態。

Thanks, Mene. This is an exciting compound, for sure. So we have a question from Simon Baker at Redburn.

謝謝，梅內。毫無疑問，這是一種令人興奮的化合物。因此，Redburn 的 Simon Baker 提出了一個問題。

And this is just one question for Dave on Calquence and ELEVATE-RR. A couple of years ago, a lot of people thought that Calquence wouldn't take off without and until the ELEVATE-RR study, and yet the sales trajectory has been very impressive in the U.S., so I wonder if you could give us your updated thoughts on the impact of ELEVATE-RR both in the U.S. market and also ex U.S. where obviously you are at a much earlier stage.

這只是 Dave 關於 Calquence 和 ELEVATE-RR 的一個問題。幾年前，很多人認為如果沒有 ELEVATE-RR 研究，Calquence 不會起飛，但在美國的銷售軌跡非常令人印象深刻，所以我想知道您是否可以向我們提供您的最新情況關於 ELEVATE-RR 在美國市場和美國以外的影響的想法，顯然你處於更早的階段。

Great. Thanks, Simon. I think I've pretty consistently been talking about the fact that our mindset in the U.S. and indeed across the globe has been that we need to be successful with Calquence irrespective of the outcome of the head-to-head study. I think the results that we talked through today and the progress that we've made certainly shows that we're doing that in the front-line setting. We did, though, take I think both a smart and a courageous risk in the head-to-head. I'm looking forward very much to sharing those results. We obviously won't have discussions about those results until they're presented. So we continue focusing in on the data that we've got in front of us. And I think that we have the belief that we've got a best-in-class agent. And we've achieved parity in the U.S. in terms of new patient share in MCL, and I see no reason why we shouldn't continue to move on that trajectory. And we have launches underway across the globe. And I'm pleased that in Germany and in the U.K. we're already starting to see positive movement within Europe and looking forward to more approvals in the front line.

偉大的。謝謝，西蒙。我想我一直在談論這樣一個事實，即我們在美國乃至全球的心態一直是，無論面對面研究的結果如何，我們都需要通過 Calquence 取得成功。我認為我們今天討論的結果和我們取得的進展肯定表明我們正在前線環境中這樣做。不過，我們確實在正面交鋒中冒了我認為既聰明又勇敢的風險。我非常期待分享這些結果。在這些結果被提交之前，我們顯然不會討論這些結果。因此，我們繼續關注擺在我們面前的數據。而且我認為我們相信我們擁有一流的代理人。就 MCL 的新患者份額而言，我們在美國實現了平等，我認為我們沒有理由不繼續沿著這條軌道前進。我們正在全球範圍內推出。我很高興在德國和英國，我們已經開始看到歐洲內部的積極進展，並期待在前線獲得更多批准。

Thanks, Dave. Next question is Peter Welford at Jefferies. (Operator Instructions) Peter, are you on mute?

謝謝，戴夫。下一個問題是 Jefferies 的 Peter Welford。 （操作員說明）彼得，你靜音了嗎？

Sorry. Can you hear me now?

對不起。你能聽到我嗎？

Maybe we can go to the...

也許我們可以去...

Sorry. Can you hear me now?

對不起。你能聽到我嗎？

Go ahead, Peter.

來吧，彼得。

Sorry, apologies for that. Just really a point of clarity, please, on the cash flow. And I don't know whether Marc can comment on this or not, but just with regards to the payouts that we should potentially be thinking about in 2021, I think you've already made 2 payments, milestones. You disclosed Daiichi. I wonder if you can give us in broad terms the other collaborations and then potentially sort of amounts we should be thinking about in terms of the potential outflows to partners during the course of 2021.

抱歉，對此深表歉意。請在現金流方面真正澄清一點。我不知道 Marc 是否可以對此發表評論，但就我們應該在 2021 年考慮的支出而言，我認為你已經支付了 2 筆款項，這是里程碑式的。你披露了第一生命。我想知道您是否可以從廣義上向我們介紹其他合作，然後是我們應該考慮的潛在金額，即 2021 年期間流向合作夥伴的潛在資金流出。

Thanks, Peter. Marc?

謝謝，彼得。馬克？

No, we don't provide this sort of schedule of payments for the year -- for the coming years, but we have -- when we have concluded the deal, the deals, we have usually indicated the various types of payment we make for each of the project. So the question then comes when is -- this triggering point is if we pay for a development milestone, an approval milestone or something else. The question becomes then when is this triggering point taking place, so I'm not going to be able to comment in detail about that. Apologies.

不，我們不提供今年——未來幾年的這種付款時間表，但我們有——當我們完成交易時，我們通常會指出我們為之支付的各種類型每個項目。那麼問題來了——這個觸發點是我們是否為開發里程碑、批准里程碑或其他東西付費。那麼問題就變成了這個觸發點是什麼時候發生的，所以我無法對此進行詳細評論。道歉。

Thanks, Marc. Emmanuel Papadakis, Deutsche Bank.

謝謝，馬克。 Emmanuel Papadakis，德意志銀行。

Maybe I'll take a quick one on Imfinzi. I mean it seems to have flattened pretty hard in the U.S. Time lines have slipped on several trials, including adjuvants. You've heard some interesting competitor studies started, including TIGIT combinations. And I don't think we've seen anything equivalent yet started in terms of pivotal trials from [AstraZeneca]. Perhaps you could just comment on the outlook. Where and when will any further big growth be coming from, from the Imfinzi side? And your perspective on competitive risks over the next few years.

也許我會快速了解 Imfinzi。我的意思是，它在美國似乎已經變得相當堅硬。時間線在幾項試驗中有所下滑，包括佐劑。您聽說開始了一些有趣的競爭對手研究，包括 TIGIT 組合。而且我認為我們還沒有看到任何與 [AstraZeneca] 的關鍵試驗類似的東西。也許你可以對前景發表評論。 Imfinzi 方面何時何地會出現進一步的大幅增長？以及您對未來幾年競爭風險的看法。

Dave?

戴夫？

Thanks, Emmanuel, for the question. So on Imfinzi, we have with the PACIFIC indication, certainly in the major early markets that we've launched, gotten to a place of standard of care. And as a result, we've seen kind of more modest sequential growth, particularly on the latter half. With that said, the CASPIAN study is an area that we are really looking forward to making continued inroads into. We have a very nice profile. It's been well received by physicians and oncologists across the globe. The pandemic has affected probably Imfinzi as an infused therapy more than it has some of the other products within the portfolio. In terms of the pipeline question that you asked, I think we highlighted some of the studies that I'm looking forward to readouts on later this year, PACIFIC-2, HIMALAYA. Both of those are important opportunities to continue growth. We also are doing our own work on TIGIT combinations in collaboration with Arcus, which is something that we've spoken to in the past or Arcus has spoken to. And so we look forward to continued news flow out of Imfinzi in the rest of the year.

謝謝，Emmanuel，提出這個問題。因此，在 Imfinzi 上，我們有 PACIFIC 適應症，當然在我們已經推出的主要早期市場，達到了護理標準。結果，我們看到了較為溫和的連續增長，尤其是在下半年。話雖如此，CASPIAN 研究是一個我們非常期待繼續深入的領域。我們的形象非常好。它受到了全球醫生和腫瘤學家的好評。與產品組合中的其他一些產品相比，大流行病對 Imfinzi 作為一種輸液療法的影響可能更大。關於您提出的管道問題，我認為我們強調了一些我期待在今年晚些時候讀出的研究，PACIFIC-2，HIMALAYA。這兩者都是繼續增長的重要機會。我們還與 Arcus 合作，在 TIGIT 組合方面開展自己的工作，這是我們過去談過或 Arcus 談過的事情。因此，我們期待在今年餘下的時間裡繼續傳出 Imfinzi 的消息。

Thanks, Dave. Naresh Chouhan at Intron Health.

謝謝，戴夫。 Intron Health 的 Naresh Chouhan。

Just one on Symbicort, please. In the U.S., we've clearly seen the benefit in 2020 from a higher adherence. Should we expect to be -- expecting a similar level for this year based on pricing and what you've seen to date in volumes? And it's quite a big number. I'm just trying to get a sense of where that's heading.

就一個 Symbicort，拜託。在美國，我們已經清楚地看到 2020 年更高的依從性帶來的好處。我們是否應該期望——根據定價和你迄今為止看到的數量，預計今年會有類似的水平？這是一個相當大的數字。我只是想了解它的發展方向。

That's for you, Ruud, I think.

那是給你的，Ruud，我想。

Yes. So it's another good question. (inaudible), but once again we are not going to comment on individual product forecasts. But Symbicort is well placed. It's the leader in the United States in the ICS/LABA class. There's a huge heritage, so we are bullish regarding the outlook, but equally we also need to mention that we are focusing our efforts more and more on Breztri as well in the COPD. We really believe that there's high unmet medical needs. The triple class is growing very, very fast. So a lot of the efforts of our field force marketing and medical teams are more and more on Breztri and less on Symbicort moving forward.

是的。所以這是另一個好問題。 （聽不清），但我們不會再一次對個別產品預測發表評論。但 Symbicort 的位置很好。在ICS/LABA類中美國領先。有一個巨大的遺產，所以我們對前景持樂觀態度，但同樣我們也需要提到我們越來越多地將我們的努力集中在 Breztri 以及 COPD 中。我們真的相信有很多未滿足的醫療需求。三班級的增長非常非常快。因此，我們的現場營銷和醫療團隊的很多努力越來越多地集中在 Breztri 上，而越來越少地集中在 Symbicort 上。

Thanks, Ruud. [Christopher Ule at Sen].

謝謝，魯德。 [Sen 的 Christopher Ule]。

So my question is about sort of COVID therapies. So the AZD7442, I guess it's the same underlying technology as nirsevimab, but the -- as I understand it, the COGS on nirsevimab are prohibitive for use in adult prophylaxis in RSV. So what can you say about this in COGS in -- with 7442? And why, if any, is there a discrepancy? And then I guess, related to COVID therapies, can you comment on -- I guess there was a recent study with Symbicort. Can you comment on how you see that opportunity?

所以我的問題是關於某種 COVID 療法。所以 AZD7442，我猜它與 nirsevimab 的基礎技術相同，但據我所知，nirsevimab 的 COGS 禁止用於 RSV 的成人預防。那麼對於 7442 的 COGS，您能說些什麼？如果有的話，為什麼會有差異？然後我想，與 COVID 療法相關，你能評論一下——我想最近有一項關於 Symbicort 的研究。你能評論一下你是如何看待這個機會的嗎？

Thanks, [Christopher]. Very quickly, the first one: Cost of goods is quite reasonable we see or in relation to the selling price of this [cocktail] (inaudible), [but this], of course, is more expensive because you have to put 2 in -- 2 antibodies in that same vial. But we don't see this as a limitation in terms of the potential of the product. Symbicort, Ruud, do you want to cover this? This is Symbicort in the COVID patients; and the study, the early study with a smaller number of patients but still quite intriguing, showing a 90% reduction of progressional disease.

謝謝，[克里斯托弗]。很快，第一個：商品成本是相當合理的，我們看到或與這種[雞尾酒]（聽不清）的售價有關，[但是這個]當然更貴，因為你必須把 2 放進去 - - 同一個小瓶中有 2 種抗體。但我們並不認為這是對產品潛力的限制。 Symbicort，Ruud，你想報導這個嗎？這是 COVID 患者的 Symbicort；這項研究是一項早期研究，患者人數較少，但仍然很有趣，顯示疾病進展率降低了 90%。

Yes. I presume it's not Symbicort. It's Pulmicort, yes. That's...

是的。我認為它不是 Symbicort。是普米克，是的。那是...

Yes, Pulmicort, yes.

是的，普米克，是的。

Yes. But it's -- without any doubt, it's a very interesting finding. The study was stopped earlier than expected because of the overwhelming efficacy. And we know, of course, that corticosteroids have a very dampening effect on the cytokine storm in COVID-19 patients. Now the implications for what it means, we're still trying to figure it out, but equally, of course, we have seen that Symbicort adherence has increased quite substantially in asthmatics. And there are more and more reports that asthmatics, because of the fact that they are using a corticosteroid, inhaled corticosteroids, are ending up less in hospitals and are showing less-severe disease than other patients. So we are following it. We are looking into it, but I think it's a little bit too early in order to get overly excited that this will be a massive sales opportunity.

是的。但毫無疑問，這是一個非常有趣的發現。由於壓倒性的療效，該研究比預期更早停止。當然，我們知道皮質類固醇對 COVID-19 患者的細胞因子風暴有非常抑製作用。現在它意味著什麼，我們仍在努力弄清楚，但同樣，當然，我們已經看到哮喘患者對 Symbicort 的依從性有了相當大的提高。越來越多的報導稱，由於使用皮質類固醇，吸入性皮質類固醇，哮喘患者住院的情況越來越少，而且病情也沒有其他患者嚴重。所以我們正在關注它。我們正在研究它，但我認為現在過早地認為這將是一個巨大的銷售機會還為時過早。

Ruud, I will just say one thing. Just we do have several studies that are ongoing with Pulmicort and Symbicort that are being run externally just to continue to follow that efficacy.

魯德，我只想說一件事。只是我們確實有幾項正在進行的關於 Pulmicort 和 Symbicort 的研究，這些研究正在外部運行，只是為了繼續遵循這種療效。

Very good. So we'll take the last question. [Martin Jole at Azman and Co.].

非常好。那麼我們來回答最後一個問題。 [Azman and Co. 的 Martin Jole]。

For a number of years, your SG&A has been more than 10 percentage points above the weighted industry average. You made some good progress in 2020 and with the increase in sales being achieved with flat underlying SG&A, but apart from increasing sales, how do you intend to get your SG&A costs more in line with the industry average? Or an alternative way of looking at it, with your current sales force, to bring your SG&A in line with the industry average, you need to have product sales of $39 billion. Do you think that's achievable?

多年來，您的 SG&A 比加權行業平均水平高出 10 個百分點以上。您在 2020 年取得了一些良好的進展，並且在基本 SG&A 持平的情況下實現了銷售額的增長，但除了增加銷售額之外，您打算如何使您的 SG&A 成本更符合行業平均水平？或者換一種看待它的方式，用你目前的銷售隊伍，要使你的 SG&A 與行業平均水平保持一致，你需要有 390 億美元的產品銷售額。你認為這是可以實現的嗎？

Marc, do you want to cover this one?

馬克，你想報導這個嗎？

Yes. I think I can only point you to the years -- the 3 past years 2018, '19, and '20; and see the progress that we have made on the SG&A ratio. We have also said that we will always put enough resources behind the launching of our new products and on new indications so that we put them on the right trajectory. So this, we will continue to do, but since we are promoting products within the focus areas where we are present, over time when the sales grow, you have this phenomenon of operating leverage at different levels but in particular on the SG&A line. So we are going to continue our effort on the operating leverage, and over time, the SG&A ratio will decline.

是的。我想我只能指出這些年——過去 3 年 2018 年、19 年和 20 年；並查看我們在 SG&A 比率方面取得的進展。我們還說過，我們將始終在新產品和新適應症的推出後投入足夠的資源，以便我們將它們置於正確的軌道上。因此，我們將繼續這樣做，但由於我們在我們所處的重點領域內推廣產品，隨著時間的推移，隨著銷售額的增長，你會在不同層面出現這種經營槓桿現象，尤其是在 SG&A 線上。因此，我們將繼續努力提高運營槓桿，隨著時間的推移，SG&A 比率將會下降。

Thanks, Marc. There is one -- maybe one last question. Seamus Fernandez at Guggenheim.

謝謝，馬克。還有一個——也許是最後一個問題。古根海姆的 Seamus Fernandez。

So mine was just on roxadustat. I know we're in kind of the final days of FDA discussions. I just wanted to get a sense of your confidence in getting the non-dialysis portion approved and if really the only source of debate is whether or not you have an ESA-like warning on CV risk.

所以我的只是在 roxadustat 上。我知道我們正處於 FDA 討論的最後幾天。我只是想了解您對獲得非透析部分批准的信心，如果真的如此，唯一的爭論來源是您是否有類似 ESA 的 CV 風險警告。

Mene, this one is for you.

梅內，這是給你的。

I can say (inaudible) confidence is high, I would say. You've kind of semi-answered the question. This is a short answer: Confidence is high.

我可以說（聽不清）信心很高，我會說。你有點半回答了這個問題。這是一個簡短的回答：信心很高。

Very good. Okay, so thank you so much, everybody. And I know we took you overtime, but there were so many questions.

非常好。好的，非常感謝大家。我知道我們讓你加班了，但問題太多了。

So I'd like to thank you very much for your interest. And we look forward to meeting you all during the global road shows. That starts tomorrow. And it's really going to be a very exciting year, lots of opportunities for us. And I look forward to the discussions. And again, once again, thank you so much for your interest. And goodbye.

所以我非常感謝你的興趣。我們期待在全球路演期間與大家見面。明天開始。這真的將是非常激動人心的一年，對我們來說有很多機會。我期待著討論。再一次，非常感謝您的關注。再見。