AstraZeneca PLC (AZN) 2022 Q3 法說會逐字稿

Good morning to those joining from the U.K. and the U.S. Good afternoon to those in Central Europe, and good evening to those listening in Asia. Welcome, ladies and gentlemen, to AstraZeneca's year-to-date and Q3 Results 2022 Conference Call for investors and analysts.

來自英國和美國的與會者早上好，中歐與會者下午好，亞洲聽眾晚上好。女士們，先生們，歡迎參加阿斯利康年初至今和 2022 年第三季度業績的投資者和分析師電話會議。

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

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

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

還請仔細閱讀本演示文稿隨附的幻燈片中的前瞻性聲明免責聲明。 （操作員說明）。

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

有了這個，我現在把你交給公司。

Thank you, operator, and good afternoon, everybody. I'm Andy Barnett, Head of Investor Relations at AstraZeneca, and I'm pleased to welcome you to AstraZeneca's third quarter and year-to-date 2022 Conference call. All materials presented today are available on our website. .

謝謝接線員，大家下午好。我是阿斯利康（AstraZeneca）投資者關係主管安迪·巴尼特（Andy Barnett），我很高興歡迎您參加阿斯利康（AstraZeneca）第三季度和年初至今的 2022 年電話會議。今天介紹的所有材料都可以在我們的網站上找到。 .

Slide 2 has our usual Safe Harbor statement. We will be making comments on our performance using constant exchange rates, or CER, core financial numbers and other non-GAAP measures, and non-GAAP to GAAP reconciliation is contained within the results announcement. Numbers are in million U.S. dollars for the first 9 months of the year, unless otherwise stated.

幻燈片 2 有我們通常的安全港聲明。我們將使用恆定匯率或 CER、核心財務數據和其他非 GAAP 措施對我們的業績發表評論，非 GAAP 與 GAAP 對賬包含在結果公告中。除非另有說明，否則今年前 9 個月的數字以百萬美元為單位。

Please advance to Slide 3. This slide shows our agenda for today's call. Following our prepared remarks, we will open the line for questions. (Operator Instructions)

請轉到幻燈片 3。這張幻燈片顯示了我們今天電話會議的議程。在我們準備好的評論之後，我們將打開提問線。 （操作員說明）

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

有了這個，請轉到幻燈片 4，我將交給 Pascal。

Hello, everyone, and welcome to today's call.

大家好，歡迎來到今天的電話會議。

If you move to Slide 5, we're pleased to report solid results with year-to-date total revenue of $33.1 billion, an increase of 37%. This includes total revenue in the quarter of close to $11 billion. On a pro forma basis, the growth rate in the year-to-date, including Alexion, was 19%. And excluding our COVID medicines, the growth was 16%, illustrating the strength of our underlying business. Core EPS of $5.28 in the year-to-date is up 52% versus the same period last year, with $1.67 added in the quarter. Of course, it helped by the addition of Alexion from July 2021.

如果您轉到幻燈片 5，我們很高興地報告穩健的業績，年初至今的總收入為 331 億美元，增長了 37%。這包括本季度近 110 億美元的總收入。在備考基礎上，包括 Alexion 在內的年初至今的增長率為 19%。不包括我們的 COVID 藥物，增長率為 16%，說明了我們基礎業務的實力。年初至今的核心每股收益為 5.28 美元，較去年同期增長 52%，本季度增加了 1.67 美元。當然，這得益於從 2021 年 7 月開始添加的 Alexion。

This performance reflects the strength of our business against the challenging macroeconomic backdrop. Our delivery in the year-to-date and near-term outlook has enabled us to upgrade our full year guidance. I would, however, point out that EPS landing in the low 30s of the guidance range will depend on certain factors, including the timing of collaboration milestones and Evusheld deliveries before the end of the year. Aradhana will take you through this change to our guidance in more detail.

這一表現反映了我們在充滿挑戰的宏觀經濟背景下的業務實力。我們在年初至今和近期展望中的交付使我們能夠升級我們的全年指導。然而，我要指出的是，EPS 是否落在指導範圍的 30 多歲將取決於某些因素，包括合作里程碑的時間安排和 Evusheld 在年底之前的交付。 Aradhana 將帶您更詳細地了解我們的指南的這一變化。

Once again, we saw encouraging demand for our medicines, with growth from all disease areas versus last year. This included double-digit growth for oncology, CVRM, V&I and Rare Disease, and the growth of new medicines more than offset the expected decline of Pulmicort within R& I.

我們再次看到對我們藥物的令人鼓舞的需求，所有疾病領域的需求都與去年相比有所增長。這包括腫瘤學、CVRM、V&I 和罕見病的兩位數增長，以及新藥的增長超過了 Pulmicort 在 R&I 中的預期下降。

Please move to Slide 6. Our R&D investment continues to pay off. We received a record 19 regulatory approvals in major markets since we reported our first half results, making of total of 25 approvals in the year-to-date, with only a selection listed on this slide.

請移至幻燈片 6。我們的研發投資繼續獲得回報。自我們報告上半年業績以來，我們在主要市場獲得了創紀錄的 19 項監管批准，今年迄今共獲得 25 項批准，這張幻燈片上僅列出了一部分。

I would, in particular, I'd like to call out the first global approvals for our CTLA4 inhibitor, Imjudo, for the treatment of advanced liver cancer and the approval of Beyfortus for the prevention of RSV in newborns and infants. We also announced positive Phase III data for 2 NMEs. Danicopan in PNH patients with clinically significant extravascular hemolysis, and capivasertib in breast cancer, both with the potential to strengthen our leading positions in their respective diseases. Additionally, we saw encouraging data for Dato-DXd and camizestrant, enabling us to engage further clinical development of this potentially important new medicines.

我特別想呼籲我們的 CTLA4 抑製劑 Imjudo 首次獲得全球批准，用於治療晚期肝癌，以及 Beyfortus 獲得批准用於預防新生兒和嬰兒 RSV。我們還公佈了 2 個 NME 的積極 III 期數據。 Danicopan 用於具有臨床意義的血管外溶血的 PNH 患者，以及 capivasertib 用於乳腺癌，兩者都有可能加強我們在各自疾病中的領先地位。此外，我們看到了 Dato-DXd 和 camizestrant 的令人鼓舞的數據，使我們能夠參與這種潛在重要的新藥的進一步臨床開發。

Please move to Slide 7. Our broad portfolio of both marketed and innovative pipeline medicines gives us confidence in our ability to deliver revenue growth at a double-digit CAGR through 2025 and include an industry-leading growth thereafter. Fundamentally, our business is highly resilient, with low concentration risk and a diverse geographical footprint and a broad pipeline. Even excluding our COVID-19 medicines, we have 11 blockbuster medicines, and we have demonstrated success in developing and commercializing medicines in a range of diseases with high unmet medical need. We have 15 NMEs in Phase III clinical development, expect to maintain or even accelerate this pace of innovation in coming years.

請移至幻燈片 7。我們廣泛的上市和創新管道藥物組合使我們有信心在 2025 年之前以兩位數的複合年增長率實現收入增長，並在此後實現行業領先的增長。從根本上說，我們的業務具有很強的彈性，集中風險低，地理足跡多樣化，渠道廣泛。即使不包括我們的 COVID-19 藥物，我們也有 11 種重磅藥物，並且我們在開發和商業化治療一系列具有高度未滿足醫療需求的疾病的藥物方面取得了成功。我們有 15 個 NME 處於 III 期臨床開發階段，預計未來幾年將保持甚至加快這一創新步伐。

While our portfolio is diverse, we are well placed to lead in fast-growing disease areas such as Oncology, Rare Disease and several areas of specialty medicine. Our broad geographical footprint allows us to offset short-term challenges in any one region, which we continue to view as an advantage versus a number of our peers. Delivering on our long-term growth ambitions will require us to continue to make the right strategic investments.

雖然我們的產品組合多樣化，但我們在快速增長的疾病領域處於領先地位，例如腫瘤學、罕見病和幾個專科醫學領域。我們廣泛的地理足跡使我們能夠抵消任何一個地區的短期挑戰，我們繼續將其視為與許多同行相比的優勢。實現我們的長期增長目標將需要我們繼續進行正確的戰略投資。

I will now hand the call to Aradhana to go through our financials, as well as provide some detail around our investments to drive future growth. So please move to Slide 8.

現在，我將致電 Aradhana 了解我們的財務狀況，並提供有關我們投資的一些細節，以推動未來的增長。所以請移到幻燈片 8。

Thank you, Pascal, and good afternoon, everyone. As usual, I will start with our reported P&L. Please turn to Slide 9.

謝謝你，帕斯卡，大家下午好。像往常一樣，我將從我們報告的損益開始。請轉到幻燈片 9。

As Pascal has already highlighted, total revenue grew by 37% in the first 9 months. As a reminder, Alexion sales were only consolidated from July 21 last year, so this impacts the revenue growth numbers favorably. Collaboration revenue increased $944 million, of which close to $400 million relates to milestones received from partners, including Merck for the Lynparza collaboration. We have booked an additional around $330 million in collaboration revenue for Enhertu. Our reported gross margin continues to be impacted by the Alexion fair value inventory uplift, which we anticipate will continue for a couple of more quarters until the inventory is sold.

正如 Pascal 已經強調的那樣，前 9 個月的總收入增長了 37%。提醒一下，Alexion 的銷售額僅從去年 7 月 21 日開始合併，因此這對收入增長數字產生了有利影響。合作收入增加了 9.44 億美元，其中近 4 億美元來自合作夥伴的里程碑，包括默克公司與 Lynparza 的合作。我們為 Enhertu 額外預訂了約 3.3 億美元的合作收入。我們報告的毛利率繼續受到 Alexion 公允價值庫存增加的影響，我們預計這將持續幾個季度，直到庫存售出。

Please turn to Slide 10. This is our core P&L. The core gross margin during the period was 81% and increased by 6 percentage points at constant exchange rates. The favorable increase in gross margin is mainly driven by lower Vaxzevria sales versus last year, and the fact that Alexion sales were only consolidated from end of July. R&D costs increased by 29%, reflecting again the timing of consolidation of Alexion last year and also continued investment in the pipeline.

請轉到幻燈片 10。這是我們的核心損益表。期內核心毛利率為81%，按固定匯率計算上升6個百分點。毛利率的有利增長主要是由於 Vaxzevria 的銷售額低於去年，以及 Alexion 的銷售額僅從 7 月底開始合併。研發成本增加了 29%，再次反映了 Alexion 去年整合的時機以及對管道的持續投資。

We've had several positive readouts this year that have ungated additional clinical trials. Over the long term, we continue to expect that we will keep R&D investments in the low 20s percentage of total revenue. SG&A costs increased by 24% year-to-date, reflecting the addition of Alexion and continued investment behind launch brands, including demand generation for Evusheld. We continue to manage SG&A costs by driving productivity and the operating margin will continue to improve as our product mix evolves between primary and specialty care. However, these will need to be balanced by our long-term growth ambition and investment for that growth as well as external factors, including inflation and currency. Core EPS of $5.28 represents a growth of 52%.

今年我們有幾個積極的讀數，這些讀數已經取消了額外的臨床試驗。從長遠來看，我們繼續期望我們將研發投資保持在總收入的 20 多歲的低百分比。今年迄今為止，SG&A 成本增加了 24%，這反映了 Alexion 的加入以及對推出品牌的持續投資，包括對 Evusheld 的需求產生。我們繼續通過提高生產力來管理 SG&A 成本，隨著我們的產品組合在初級和專科護理之間的演變，營業利潤率將繼續提高。然而，這些都需要通過我們的長期增長雄心和對該增長的投資以及包括通貨膨脹和貨幣在內的外部因素來平衡。核心每股收益為 5.28 美元，增長了 52%。

Please turn to Slide 11. Our cash flow continues to improve, and we saw cash flow generated from operating activities increase by $2.9 billion to $7.4 billion in the first 9 months. In the third quarter, we paid 3 regulatory milestones totaling $400 million to Daiichi Sankyo following regulatory approvals for Enhertu in both breast and lung cancer. We also paid the last of the 3 initial upfront payments of $325 million relating to Dato-DXd and as well as $100 million for the [Teneo 2] acquisition, which closed during the third quarter. This brings the total amount paid year-to-date for the Daiichi Sankyo, [Acerta] and other transactions to just over $2 billion.

請轉到幻燈片 11。我們的現金流繼續改善，前 9 個月經營活動產生的現金流增加了 29 億美元，達到 74 億美元。在第三季度，在 Enhertu 在乳腺癌和肺癌方面的監管批准後，我們向第一三共支付了 3 個監管里程碑，總計 4 億美元。我們還支付了與 Dato-DXd 相關的 3.25 億美元的 3 筆初始預付款中的最後一筆，以及在第三季度完成的 [Teneo 2] 收購的 1 億美元。這使得第一三共、[Acerta] 和其他交易今年迄今支付的總金額剛剛超過 20 億美元。

Our current net debt-to-EBITDA ratio is 2.9x. If adjusting for the Alexion fair value inventory uplift, which does not affect our cash flow, the ratio is 1.9x, a reflection of the improvement in our underlying cash flow. Our cash conversion ratio continues to improve, and we continue to focus on working capital improvement, inventory management and cash conversion. We remain committed to a strong investment-grade rating and our capital allocation policy priorities remain unchanged.

我們目前的淨債務與 EBITDA 比率為 2.9 倍。如果調整不影響我們現金流的 Alexion 公允價值庫存提升，該比率為 1.9 倍，這反映了我們基礎現金流的改善。我們的現金轉換率不斷提高，我們繼續專注於營運資金改善、庫存管理和現金轉換。我們仍致力於維持強勁的投資級評級，我們的資本配置政策重點保持不變。

Please turn to Slide 12. As a reminder, we upgraded our total revenue guidance at half year results. Today, we are updating our core EPS guidance for the full year. We continue to expect total revenue to grow by low 20s percentage. Despite being in early November, there continue to be several variables that we are monitoring in the fourth quarter, including Evusheld delivery, NRDL update and VVP implementation with potential stock compensation, and the timing of some approvals with associated milestones. For the full year, we now anticipate core EPS to grow by high 20s to low 30s percentage at constant exchange rate, up from previously mid to high 20s.

請轉到幻燈片 12。提醒一下，我們在半年業績時上調了總收入指引。今天，我們正在更新全年的核心每股收益指引。我們繼續預計總收入將以 20% 的低百分比增長。儘管是在 11 月初，但我們在第四季度繼續監測幾個變量，包括 Evusheld 交付、NRDL 更新和 VVP 實施以及潛在的股票補償，以及一些具有相關里程碑的批准的時間。對於全年，我們現在預計核心每股收益將以固定匯率從 20 年代高到 30 年代低百分比增長，從之前的 20 年代中期到 20 年代高。

Although the phasing of expenses in the second half resulted in strong profitability in the third quarter, we expect higher operating costs, particularly SG&A in the fourth quarter, similar to the sequential quarterly increase in prior years. As we report in U.S. dollars, we faced some currency headwinds with all of our key currencies having depreciated versus the U.S. dollar. Based on spot rates as per the end of October 2022, we continue to anticipate a mid-single-digit adverse FX impact on total revenue for the full year. For core EPS, we now anticipate a mid to high single-digit adverse impact for the full year that is somewhat higher than what we anticipated back in July and reflects further depreciation of our key currencies. This is something to bear in mind when you update your models.

儘管下半年分階段的支出導致第三季度的盈利能力強勁，但我們預計第四季度的運營成本，尤其是 SG&A，與往年的季度環比增長相似。當我們以美元報告時，我們面臨一些貨幣逆風，我們所有的主要貨幣都對美元貶值。根據截至 2022 年 10 月的即期匯率，我們繼續預計全年總收入將受到中個位數的不利外匯影響。對於核心每股收益，我們現在預計全年會有中到高個位數的不利影響，這比我們在 7 月份的預期要高一些，反映了我們的主要貨幣進一步貶值。更新模型時要牢記這一點。

Please turn to Slide 13. I have previously mentioned that we anticipate keeping R&D investments in the low 20s percentage of total revenue, also over the mid to long term. Today, just over 50% of our total R& D spend is invested in late-stage pipeline, including extensive LTM programs for already-launched medicines. About 40% R&D budget is invested in early-stage pipeline and discovery focusing on novel therapies, generating proof of concept and building our in-house portfolio of next-generation medicines, including ADCs, bi-specifics and complement therapies. This will help fuel our pipeline beyond 2025.

請轉到幻燈片 13。我之前提到過，我們預計研發投資在總收入中的低 20 百分比，也是在中長期內。今天，我們總研發支出的 50% 以上投資於後期管道，包括針對已推出藥物的廣泛 LTM 計劃。大約 40% 的研發預算投資於早期管道和發現，專注於新療法、產生概念證明並建立我們的內部下一代藥物組合，包括 ADC、雙特異性和補充療法。這將有助於推動我們在 2025 年之後的管道。

The majority of the remaining part of the R&D budget is invested in global medical affairs which is focused on real-world data generation and medical education, including driving guideline and practice change. This area of spend has become very important, with our portfolio shifting into more specialty areas.

剩餘研發預算的大部分投資於全球醫學事務，專注於現實世界的數據生成和醫學教育，包括推動指南和實踐的改變。隨著我們的投資組合轉向更多專業領域，這一支出領域變得非常重要。

We have a very disciplined investment approach where we set high bars from both a scientific and commercial perspective for the assets that we progress into late-stage development. A good example is our PCSK9, which we terminated in the quarter despite having positive data, but it did not meet our high predefined criteria required for progressing into Phase III development. Our commercial investments include launching new products, new indications in existing markets and existing products in new markets. Good examples are Enhertu low breast cancer and Lynparza and prostate cancer, where considerable market shaping is required.

我們有一個非常嚴格的投資方法，我們從科學和商業的角度為我們進入後期開發的資產設定了高標準。一個很好的例子是我們的 PCSK9，儘管有積極的數據，但我們在本季度終止了它，但它不符合我們進入第三階段開發所需的高預定義標準。我們的商業投資包括在現有市場推出新產品、新適應症以及在新市場推出現有產品。很好的例子是 Enhertu 低位乳腺癌和 Lynparza 和前列腺癌，它們需要相當大的市場塑造。

Please turn to Slide 14. With our culture of continuous improvement, we have been working hard to drive productivity and cost savings. Just to share some examples today, we have worked to optimize our manufacturing network between in-house and external CMOs, as well as build new capabilities such as continuous manufacturing to make us more efficient and flexible. We're also looking at our global footprint, enhancing how we work, leveraging low-cost location and growing our global shared service centers. We're making great progress on the integration of Alexion, recently moving to a direct, easy distribution model in more than 22 markets. I'm pleased to share that we now have a rare disease unit in China. We have been on a journey shifting late-age clinical trials from an outsourced model to a more mixed and in-house model that provides greater data control and better trial execution in a more cost-effective manner. Over time, the investments we are doing today will help accelerate clinical trials and shorten the time needed for regulatory submission, which will allow us to launch new medicines quicker in the future.

請轉到幻燈片 14。憑藉我們不斷改進的文化，我們一直在努力提高生產力和節約成本。今天只是分享一些例子，我們一直在努力優化內部和外部 CMO 之間的製造網絡，並建立新的能力，例如連續製造，以提高我們的效率和靈活性。我們也在關注我們的全球足跡，改進我們的工作方式，利用低成本的位置並發展我們的全球共享服務中心。我們在整合 Alexion 方面取得了很大進展，最近在超過 22 個市場轉向了直接、簡單的分銷模式。我很高興與大家分享我們現在在中國設立了一個罕見病部門。我們一直在將晚期臨床試驗從外包模型轉變為更加混合和內部模型，以更具成本效益的方式提供更好的數據控制和更好的試驗執行。隨著時間的推移，我們今天所做的投資將有助於加速臨床試驗並縮短監管提交所需的時間，這將使我們能夠在未來更快地推出新藥。

With that, please advance to the next slide, and I will hand over to Dave, who will take us through the performance of our Oncology business.

有了這個，請轉到下一張幻燈片，我將交給 Dave，他將帶我們了解我們腫瘤業務的表現。

Thank you, Aradhana. Slide 16, please.

謝謝你，阿拉達納。請幻燈片 16。

We're pleased to report that our Oncology total revenue grew 24% year-over-year during the first 9 months of 2022, underpinned by 20% growth in product sales. We saw double-digit product sales growth for Tagrisso, Imfinzi and Lynparza in the period, as well as very strong continuing momentum for both Calquence and Enhertu. Across regions, performance was again nicely balanced with the U.S., Europe emerging markets and established Rest of World each also driving double-digit year-on-year growth. As COVID-19 moves into an endemic phase, we've seen improved rates of cancer diagnosis, testing and treatment during the year. There is still some variability across tumor type and region, notably China where city lockdowns persist, but we remain optimistic on the underlying global trend.

我們很高興地報告，在產品銷售增長 20% 的支持下，我們的腫瘤學總收入在 2022 年前 9 個月同比增長 24%。我們看到 Tagrisso、Imfinzi 和 Lynparza 在此期間實現了兩位數的產品銷售增長，以及 Calquence 和 Enhertu 的強勁持續增長勢頭。在各個地區，業績再次與美國、歐洲新興市場和成熟的世界其他市場取得了很好的平衡，每個市場也都推動了兩位數的同比增長。隨著 COVID-19 進入流行階段，我們看到這一年的癌症診斷、檢測和治療率有所提高。腫瘤類型和地區之間仍然存在一些差異，特別是中國的城市封鎖持續存在，但我們對潛在的全球趨勢保持樂觀。

Turning now to individual medicine performance. Tagrisso global revenues grew by 16% year-to-date. In the U.S., growth was 14%, with Q3 growing at 18%, reflecting continued momentum for FLAURA and LAURA. In Emerging Markets, revenues grew 22%, with a strong contribution from China and Latin America. EM growth of Q3 of 35% benefited from strong FLAURA volume growth and second line resilience in China, but also reflects a fairly easy comparison to last year's Q3. Tagrisso and Lynparza both face China NRDL renewal for 2023 to 2024 in Q4. We anticipate both medicines will incur some price reduction as a result of algorithm-based adjustments. .

現在轉向個人醫學表現。 Tagrisso 全球收入今年迄今增長了 16%。在美國，增長 14%，第三季度增長 18%，反映了 FLAURA 和 LAURA 的持續增長勢頭。在新興市場，收入增長了 22%，其中中國和拉丁美洲的貢獻很大。第三季度新興市場增長 35% 得益於強勁的 FLAURA 銷量增長和中國二線市場的韌性，但也反映出與去年第三季度相比相當容易。 Tagrisso 和 Lynparza 都在第四季度面臨 2023 年至 2024 年的中國 NRDL 更新。由於基於算法的調整，我們預計這兩種藥物都會導致價格有所下降。 .

In Established Rest of World, Tagrisso growth was 10% year-to-date. In Japan, we can now confirm that we anticipate a mandatory price reduction that will be applied in 2023. For Lynparza, we continue to solidify the brand leader in the global PARP inhibitor class. Product sales grew 19% in the quarter and year-to-date, led by growth in adjuvant breast cancer following this year's approvals in the U.S., Europe and Japan, with continued global growth in HRD-positive ovarian cancer and second-line castration-resistant prostate cancer.

在已建立的世界其他地區，Tagrisso 年初至今的增長率為 10%。在日本，我們現在可以確認，我們預計將在 2023 年實施強制性降價。對於 Lynparza，我們將繼續鞏固全球 PARP 抑製劑類別的品牌領導者。本季度和年初至今的產品銷售額增長了 19%，這主要得益於今年在美國、歐洲和日本獲得批准後輔助性乳腺癌的增長，以及全球 HRD 陽性卵巢癌和二線去勢的持續增長-耐藥性前列腺癌。

Slide 17, please. Turning now to Imfinzi, Calquence and Enhertu. All 3 benefited from good launch performances in [Q3]. Imfinzi Global revenues grew 19% year-to-date and 26% in the third quarter, with strength in the Pacific indication owing to recovery in lung cancer diagnosis and chemoradiation rates in many regions and the successful launch of TOPAZ-1 in biliary tract cancer in the U.S. Historically, the prognosis for patients with advanced BTC has been very poor, with less than 15% surviving for 5 years. TOPAZ-1 brings the first I-O treatment to this setting, one that meaningfully extend survival. We've been pleased with the early performance, with wrap uptake following on CCN inclusion and a strong commercial launch.

請幻燈片 17。現在轉向 Imfinzi、Calquence 和 Enhertu。所有 3 家都受益於 [Q3] 的良好發布表現。 Imfinzi 全球收入今年迄今增長 19%，第三季度增長 26%，由於許多地區肺癌診斷和放化療率的恢復以及膽道癌 TOPAZ-1 的成功推出，太平洋地區的適應症表現強勁在美國，從歷史上看，晚期 BTC 患者的預後一直很差，存活 5 年的患者不到 15%。 TOPAZ-1 為這種環境帶來了第一個 I-O 治療，一種有意義地延長生存期的治療。我們對早期的表現感到滿意，在 CCN 納入和強大的商業發布之後得到了總結。

Turning to Hematology. Calquence continues to show excellent momentum with worldwide revenues up 77% year-to-date. In the U.S., Calquence maintained greater than 55% share of new BTKI starts in first-line CLL, underscoring its position as the clear standard of care. Calquence U. S. revenues grew 15% sequentially in Q3. About half of that came from inventory build for the launch of the [Mali] tablet formation. This approval is important as it removes restrictions on concomitant use with proton pump inhibitors. Together with Calquence's strong data, including an attractive CV safety profile, nearly 4 years of long-term follow-up and the positive experience of physicians, we are well positioned for continued momentum as the established standard of care.

轉向血液學。 Calquence 繼續顯示出良好的勢頭，今年迄今全球收入增長了 77%。在美國，Calquence 在一線 CLL 的新 BTKI 啟動中保持超過 55% 的份額，突顯了其作為明確護理標準的地位。 Calquence 美國第三季度收入環比增長 15%。其中大約一半來自為推出 [Mali] 平板電腦而建立的庫存。該批准很重要，因為它消除了對與質子泵抑製劑同時使用的限制。再加上 Calquence 的強大數據，包括有吸引力的 CV 安全性概況、近 4 年的長期隨訪和醫生的積極經驗，我們已做好準備，作為既定的護理標準繼續保持勢頭。

In Europe, expansion continues, resulting in 25% sequential growth from Q2. New patient share continues to rise as we rapidly establish leadership in several major markets. Year-to-date, sales tripled over the same period in 2021.

在歐洲，擴張仍在繼續，導致第二季度環比增長 25%。隨著我們在幾個主要市場迅速確立領導地位，新患者的份額繼續上升。年初至今，銷售額比 2021 年同期增長了兩倍。

Finally, for Enhertu, total revenue was up 165% to $387 million, with a clear acceleration in Q3. In the U.S., Enhertu continued its gains in second-line HER2-high metastatic breast cancer, achieving 45% new patient share in just 5 months post-launch of DBO 3. The August launch of DESTINY-Breast04 and HER2-low patients has gone very well, too. Enhertu is now being utilized in more than 1/3 of the prevalent advanced HR-positive post-chemo population. New starts span multiple later lines of therapy, suggesting some bolus effect.

最後，對於 Enhertu，總收入增長 165% 至 3.87 億美元，第三季度明顯加速。在美國，Enhertu 在二線 HER2-high 轉移性乳腺癌中繼續取得進展，在 DBO 3推出後僅 5 個月內就實現了 45% 的新患者份額。8 月推出的 DESTINY-Breast04 和 HER2-low 患者已經過去也很好。 Enhertu 現在被用於超過 1/3 的普遍晚期 HR 陽性化療後人群。新的開始跨越多個後來的治療線，表明有一些推注效應。

Europe and emerging markets have contributed nicely to growth, too, with the European launch in second-line HER2-high following a similar path to the U.S. with Enhertu at more than 35% new patient share in Germany and France in its launch quarter. Across continue to be in an exciting period of launch activity, most recently, the U.S. approvals of Imjudo plus Imfinzi based upon HIMALAYA in liver cancer, and we look forward to upcoming approvals of Lynparza PROPEL in prostate cancer.

歐洲和新興市場也對增長做出了很好的貢獻，歐洲在二線 HER2-high 中的推出與美國類似，Enhertu 在其推出季度在德國和法國的新患者份額超過 35%。跨越繼續處於激動人心的發射活動時期，最近，美國批准了基於喜馬拉雅的 Imjudo plus Imfinzi 治療肝癌，我們期待即將批准 Lynparza PROPEL 治療前列腺癌。

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

我現在將移交給 Susan，她將介紹我們管道的進展情況。

Thank you, Dave. Please turn to the next slide.

謝謝你，戴夫。請翻到下一張幻燈片。

We had another strong presence at ESMO this year, showcasing our commitment to long-term follow-up, demonstrating the long duration of benefit that patients receive from class-leading medicines like Tagrisso and Lynparza. Additionally, we presented encouraging early data from the first of our bi-specific molecules in lung cancer.

今年我們在 ESMO 再次強勢亮相，展示了我們對長期隨訪的承諾，展示了患者從 Tagrisso 和 Lynparza 等一流藥物中獲得的長期益處。此外，我們提供了來自我們第一個肺癌雙特異性分子的令人鼓舞的早期數據。

Tagrisso demonstrated 5.5-year median disease-free survival in the adjuvant setting, with nearly 3 in 4 patients alive and disease-free at 4 years. Exploratory analysis also showed reduced risk of disease recurrence in the brain or spinal cord by 76%. This is truly amazing to see. Just 2 years ago, patients with early-stage EGFR-mutated lung cancer had no targeted treatment options after surgery.

Tagrisso 在輔助治療中表現出 5.5 年的中位無病生存期，近四分之三的患者在 4 年時仍存活且無病。探索性分析還顯示，大腦或脊髓疾病復發的風險降低了 76%。這真是令人驚奇。就在 2 年前，早期 EGFR 突變肺癌患者在手術後還沒有靶向治療方案。

Similarly, follow-up for patients in the [PAOLA-1] Phase III trial in ovarian cancer saw 65% of HRD-positive patients treated with Lynparza plus bevacizumab alive at 5 years versus 48% of those on the control arm. The overall survival benefit was observed in the HRD-positive group, a prespecified descriptive analysis for the PAOLA-1 trial.

同樣，在 [PAOLA-1] III 期卵巢癌試驗患者的隨訪中，65% 的 HRD 陽性患者接受 Lynparza 加貝伐單抗治療後 5 年仍存活，而對照組為 48%。在 HRD 陽性組中觀察到了總體生存獲益，這是 PAOLA-1 試驗的預設描述性分析。

Lastly, our new PD1-CTLA4 bi-specific, [Volustemig], formerly [MEDI5752], presented first clinical data in non-small cell lung cancer. [Vollustomag] was engineered to block CTLA-4 in the presence of PD-1 on activated T cells, improving the therapeutic index and resulting in a favorable toxicity profile when compared to concurrent use of the separate separate of the across various tumors.

最後，我們新的 PD1-CTLA4 雙特異性藥物 [Volustemig]，以前的 [MEDI5752]，首次展示了非小細胞肺癌的臨床數據。 [Vollutomag] 被設計用於在活化 T 細胞上存在 PD-1 的情況下阻斷 CTLA-4，與同時使用不同腫瘤的單獨分離相比，提高治療指數並產生有利的毒性特徵。

Please turn to Slide 19. Two weeks ago, we were delighted to share news of significant progress in our breast cancer pipeline with positive readouts for camizestrant and capivasertib. Camizestrant, our next-generation oral SERD, met the primary endpoint in the SERENA-2 Phase II trial by delivering superior progression-free survival versus Faslodex in patients with previously-treated advanced ER-positive breast cancer. We believe these data strongly point to camizestrant's best-in-class potential. The camizestrant clinical research program will evaluate multiple hypotheses in ER-driven disease, including in SERENA-6, a pivotal trial in patients whose cancer has developed ESR1 mutations.

請轉到幻燈片 19。兩週前，我們很高興地分享了我們的乳腺癌管道取得重大進展的消息，其中 camizestrant 和 capivasertib 的讀數呈陽性。 Camizestrant 是我們的下一代口服 SERD，通過在先前治療的晚期 ER 陽性乳腺癌患者中提供優於 Faslodex 的無進展生存期，達到了 SERENA-2 II 期試驗的主要終點。我們相信這些數據有力地表明了 camizestrant 的一流潛力。 camizestrant 臨床研究計劃將評估 ER 驅動疾病的多種假設，包括 SERENA-6，這是一項針對癌症已發生 ESR1 突變的患者的關鍵試驗。

It was fantastic to see capivasertib, our potential first-in-class AKT inhibitor, deliver a positive Phase III trial in advanced estrogen receptor-positive breast cancer. CAPItello-291 met both primary endpoints, improving progression-free survival in the overall patient population and in a prespecified biomarker subgroup with qualifying genetic alterations. These results indicate a new potential to (inaudible), allowing patients to continue with endocrine therapy by combining with the medicine, which targets the key pathway for endocrine therapy resistance.

很高興看到我們潛在的一流 AKT 抑製劑 capivasertib 在晚期雌激素受體陽性乳腺癌中進行了積極的 III 期試驗。 CAPItello-291 達到了兩個主要終點，提高了整個患者群體和具有合格基因改變的預先指定的生物標誌物亞組的無進展生存期。這些結果表明了一種新的潛力（聽不清），允許患者通過結合藥物繼續內分泌治療，該藥物針對內分泌治療抵抗的關鍵途徑。

Please advance to Slide 20. Finally, a look at into our plans to continue to deliver innovation to lung cancer patients.

請轉到幻燈片 20。最後，看看我們繼續為肺癌患者提供創新的計劃。

TROPION-Lung07 is a Phase III trial exploring Dato-DXd in combination with pembrolizumab, replacing platinum chemotherapy in the non-squamous PD-L1 less than 50% population to demonstrate superiority over the standard of care. From our DNA damage response portfolio, we have initiated the LATIFY Phase III trial of celarasertib plus Imfinzi post-IO (inaudible) lung cancer. Celarasertib's selective AR inhibition can cause an accumulation of double-strand DNA breaks, synergistic with checkpoint inhibition. But additionally, we have data showing celarasertib effect on increasing type 1 interferons and its ability to modulate the tumor microenvironment, including effects on myeloid III cells, thereby potentially overcoming IO resistance.

TROPION-Lung07 是一項 III 期試驗，探索 Dato-DXd 與 pembrolizumab 聯合使用，在不到 50% 的非鱗狀 PD-L1 人群中替代鉑化療，以證明其優於護理標準。從我們的 DNA 損傷反應組合中，我們啟動了 celarasertib 加 Imfinzi IO 後（聽不清）肺癌的 LATIFY III 期試驗。 Celarasertib 的選擇性 AR 抑制可導致雙鏈 DNA 斷裂的積累，與檢查點抑制協同作用。但此外，我們有數據顯示 celarasertib 對增加 1 型乾擾素的影響及其調節腫瘤微環境的能力，包括對骨髓 III 細胞的影響，從而可能克服 IO 抗性。

Finally, we're very excited to debut the second antibody drug conjugate to come from our internal team, AZD9592. AZD9592 is our first bi-specific ADC that has preferential binding in the presence of both EGFR and cMET expression aimed to direct binding distinctly to cancers, thereby sparing normal tissue. It is this that results in a maximization of efficacy whilst maintaining a favorable safety profile. This molecule utilizes our proprietary topoisomerase-1 inhibitor warhead, and we're looking to develop it in EGFR mutant non-small cell lung cancer patients, particularly in combination with Tagrisso, but also in (inaudible) type patients.

最後，我們很高興推出來自我們內部團隊的第二個抗體藥物偶聯物 AZD9592。 AZD9592 是我們的第一個雙特異性 ADC，它在 EGFR 和 cMET 表達存在的情況下具有優先結合，旨在直接與癌症明顯結合，從而保護正常組織。正是這導致了功效的最大化，同時保持了良好的安全性。該分子利用我們專有的拓撲異構酶-1抑製劑彈頭，我們正在尋求在 EGFR 突變的非小細胞肺癌患者中開發它，特別是與 Tagrisso 聯合使用，但也用於（聽不清）類型的患者。

Please advance to the next slide, and I'll hand over to Ruud to cover BioPharmaceuticals.

請轉到下一張幻燈片，我將交給 Ruud 來介紹 BioPharmaceuticals。

Thank you, Susan. Now turning to Slide 22.

謝謝你，蘇珊。現在轉到幻燈片 22。

BioPharmaceuticals delivered over $15 billion in sales year-to-date, reflecting 21% growth at constant exchange rate. Performance in the third quarter contributed $4.7 billion, a 4% increase at CER driven by underlying strength of our diverse portfolio. CVRM delivered almost $7 billion in the year-to-date, with Farxiga delivering its third consecutive blockbuster quarter and is now reimbursed in 101 countries for CKD and 112 countries for heart failure.

生物製藥今年迄今的銷售額超過 150 億美元，按固定匯率計算增長了 21%。第三季度的業績貢獻了 47 億美元，在我們多元化投資組合的潛在實力的推動下，CER 增長了 4%。 CVRM 今年迄今已交付近 70 億美元，其中 Farxiga 連續第三個季度交付重磅炸彈，目前在 101 個國家的 CKD 和 112 個國家的心力衰竭報銷。

In our Respiratory & Immunology business, strong performance of recent launch medicines offset the continued decline of Pulmicort following VBP inclusion in the prior year, leading to 4% growth overall at constant exchange rate, inclusive of of milestones. Exiting the third quarter, Fasenra is the established market leader in severe eosinophilic asthma and achieve expanded leadership within the IL-5 class, with year-to-date revenues exceeding $1 billion. Tezspire spine achieved 17% new-to-brand market share, with roughly 70% of utilization coming from patients who are new to biologics. Saphnelo continues to gain market share in the overall SMB market and achieved 48% new-to-brand share of the IV market.

在我們的呼吸和免疫學業務中，最近推出的藥物的強勁表現抵消了 Pulmicort 在上一年納入 VBP 後的持續下滑，導致按恆定匯率計算的整體增長 4%，包括里程碑。退出第三季度後，Fasenra 已成為嚴重嗜酸性粒細胞哮喘領域公認的市場領導者，並在 IL-5 類別中擴大了領導地位，今年迄今的收入超過 10 億美元。 Tezspire 脊柱獲得了 17% 的新品牌市場份額，其中大約 70% 的利用率來自對生物製劑不熟悉的患者。 Saphnelo 繼續在整個 SMB 市場獲得市場份額，並在 IV 市場取得了 48% 的新品牌份額。

Our V&I portfolio delivered $3.7 million in the year-to-date, and as expected, we saw a sharp decline in Vaxzevria sales in the third quarter due to the conclusion of initial contacts and softening demand, while Evusheld delivered $537 million in the third quarter revenues, reflecting initial demand generation efforts. Evusheld continues to play an important role around the world, protecting the immunocompromised who have no other option of protection against COVID-19.

今年迄今為止，我們的 V&I 投資組合交付了 370 萬美元，正如預期的那樣，由於初步接觸的結束和需求疲軟，我們看到第三季度 Vaxzevria 銷售額急劇下降，而 Evusheld 在第三季度交付了 5.37 億美元收入，反映了最初的需求產生努力。 Evusheld 繼續在世界範圍內發揮重要作用，保護免疫功能低下的人，他們別無選擇，可以抵禦 COVID-19。

Looking ahead to 2023, we expect fundamentals will continue to drive growth despite certain previously-mentioned dynamics, including, [Symbicort]patent expiry in the U. S. as well as the full impact of Seloken, ZOK, VBP including in China, which we anticipate taking effect this month.

展望 2023 年，我們預計基本面將繼續推動增長，儘管存在某些先前提到的動態，包括 [Symbicort] 在美國的專利到期，以及 Seloken、ZOK、VBP 的全面影響，包括在中國，我們預計會採取本月生效。

With that, I will now turn the call over to Mene to cover our BioPharmaceuticals pipeline.

有了這個，我現在將把電話轉給 Mene 來報導我們的生物製藥管道。

Thank you, Ruud, and please turn to Slide 23.

謝謝你，Ruud，請轉到幻燈片 23。

During the quarter, we presented data across our BioPharmaceuticals portfolio. In CVRM, as mentioned last quarter, we presented results from Farxiga's DELIVER trial at ESC. The analysis showed that Farxiga reduced the risk of cardiovascular death by 18% in patients with heart failure with preserved ejection fraction. In addition, a prespecified pooled analysis of DAPA-HF in the liver demonstrated a reduction in CV deaths of 14%, a reduction in death from (inaudible) by 10% in heart failure patients, irrespective of ejection fraction. These important [mix] sets confirm Farxiga's efficacy in preventing and delaying cardiorenal disease.

在本季度，我們提供了整個生物製藥產品組合的數據。如上個季度所述，在 CVRM 中，我們展示了 Farxiga 在 ESC 的 DELIVER 試驗結果。分析表明，Farxiga 將射血分數保留的心力衰竭患者的心血管死亡風險降低了 18%。此外，肝臟中 DAPA-HF 的預設匯總分析表明，無論射血分數如何，心力衰竭患者的 CV 死亡人數減少 14%，（聽不清）死亡人數減少 10%。這些重要的 [mix] 組證實了 Farxiga 在預防和延緩心腎疾病方面的功效。

At ISA, we presented interim analysis from the eplontersen Phase III NEURO-TTRansform trial in hereditary transthyretin-mediated amyloid polyneuropathy. Eplontersen demonstrated a greater than 80% mean reduction in the co-primary endpoint of serum TTR concentration and improved symptoms and quality of life in patients with polyneuropathy, and we look forward to sharing these results with the regulators.

在 ISA，我們介紹了 eplontersen III 期 NEURO-TTRansform 試驗在遺傳性轉甲狀腺素介導的澱粉樣多發性神經病中的中期分析。 Eplontersen 證明血清 TTR 濃度的共同主要終點平均降低了 80% 以上，並改善了多發性神經病患者的症狀和生活質量，我們期待與監管機構分享這些結果。

Please move to Slide 24. Last week, a long-acting RSV antibody, be Fortis was approved in the EU, and this week, it was also approved in the U.K. Beyfortus has the potential to transform RSV protection as the first and only single-dose preventive option for the broad infant population. Approval was based off our MELODY/MEDLEY clinical program, which demonstrated a 79.5% efficacy against medically-attended lower respiratory tract infection caused by RSV. Importantly, that efficacy was shown over the full length of the RSV season.

請移至幻燈片 24。上週，長效 RSV 抗體 be Fortis 在歐盟獲得批准，本週在英國也獲得批准。 Beyfortus 有可能將 RSV 保護轉變為第一個也是唯一一個單一的-廣泛嬰兒人群的劑量預防選擇。批准基於我們的 MELODY/MEDLEY 臨床計劃，該計劃證明對 RSV 引起的就醫下呼吸道感染有 79.5% 的療效。重要的是，這種功效在整個 RSV 季節都顯示出來。

At ERS, we presented the results from the long-term extension trial DESTINATION, which confirm the long-term efficacy and safety profile for Tezspire, consistent with previously reported PATHWAY and NAVIGATOR studies. In NAVIGATOR, Tezspire demonstrated a sustained reduction in the annualized asthma exacerbation rate, over 104 weeks of 58%, irrespective of inflammatory biomarkers.

在 ERS，我們展示了長期擴展試驗 DESTINATION 的結果，該結果證實了 Tezspire 的長期療效和安全性，與之前報導的 PATHWAY 和 NAVIGATOR 研究一致。在 NAVIGATOR 中，無論炎症生物標誌物如何，Tezspire 都顯示出每年哮喘發作率持續下降，超過 104 周達 58%。

During the period, we also provided an update on the results from the [MESENA] Phase III trial in eosinophilic esophagitis. [Pacena] achieved in a complete depletion of tissue eosinophils consistent with its mechanism of action, however, this did not translate into an improvement in (inaudible) symptoms. We will continue to analyze the complete data set to share with the scientific community.

在此期間，我們還提供了 [MESENA] 嗜酸性食管炎 III 期試驗結果的更新。 [Pacena] 實現了與其作用機制一致的組織嗜酸性粒細胞的完全消耗，然而，這並沒有轉化為（聽不清）症狀的改善。我們將繼續分析完整的數據集，與科學界分享。

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

請移至下一張幻燈片，我現在將由 Marc 介紹罕見病。

Thank you, Mene, and please turn to Slide 26.

謝謝你，Mene，請轉到幻燈片 26。

Year-to-date, Rare Disease total revenue grew 10% on a pro forma basis, contributing $5.2 billion. Over this period, we saw continued durability of our C5 franchise with increasing conversion to Ultomiris across PNH, atypical HUS, myasthenia gravis, as well as strong demand for Strensiq in HPP. Performance in the period also benefited from geographic expansion across our Rare Disease portfolio.

年初至今，罕見病總收入在備考基礎上增長了 10%，貢獻了 52 億美元。在此期間，隨著 PNH、非典型 HUS、重症肌無力以及 HPP 對 Strensiq 的強勁需求，我們看到了 C5 特許經營權的持續耐用性。該期間的表現也受益於我們罕見病產品組合的地域擴張。

In the third quarter, Rare Disease contributed over $1.7 billion in total revenues, representing 11% pro forma growth at constant exchange rate. The C5 franchise grew 8% with Soliris declining 6% in the quarter, reflecting the successful conversion to Ultomiris in PNH, atypical HUS and myasthenia gravis. Conversion was partially offset by growth in NMO, where Soliris remains the market share leader.

第三季度，罕見病貢獻了超過 17 億美元的總收入，按固定匯率計算，預計增長 11%。 C5 特許經營權增長 8%，而 Soliris 在本季度下降 6%，反映了 PNH、非典型 HUS 和重症肌無力患者成功轉換為 Ultomiris 的情況。轉換被 NMO 的增長部分抵消，Soliris 仍然是市場份額的領導者。

Ultomiris delivered growth of 47% in the third quarter, driven by expansion into new markets as well as the acceleration of the [GMO], with the myasthenia gravis launch in the United States.

Ultomiris 在第三季度實現了 47% 的增長，這得益於向新市場的擴張以及 [GMO] 的加速發展，以及重症肌無力在美國的推出。

Beyond the C5 franchise, Strensiq delivered 20% growth in the quarter, driven by strong demand in the United States. Koselugo, now available in 20 markets also contributed significant growth in the quarter and was granted priority review in China.

除了 C5 特許經營權之外，在美國強勁需求的推動下，Strensiq 在本季度實現了 20% 的增長。現已在 20 個市場推出的 Koselugo 在本季度也貢獻了顯著增長，並在中國獲得了優先審查。

In the third quarter, performance across the U. at constant exchange rate. S., Europe and Established Rest of the World was stable, while emerging market growth of 61% in reflects variability over the timing in certain tender markets when comparing to higher year periods.

第三季度，美國各地按固定匯率計算。南美、歐洲和世界其他地區穩定，而新興市場 61% 的增長反映了某些招標市場與較高年份相比的時間變化。

On Slide 27, I'd like to take a few moments to review highlights from our Rare Disease event, the full recording of which is available on our website.

在幻燈片 27 上，我想花點時間回顧一下我們罕見病活動的亮點，我們的網站上提供了完整的記錄。

We remain leaders in Rare Disease with our pioneering C5 franchise, which will deliver growth in the near to midterm, and our novel complement and beyond complement medicine, which will help support AstraZeneca longer growth ambitions. We announced Ultomiris will be available in 85 countries by the end of next year and indicated plans to pursue launch and expansion for cardiac surgery-associated [AKI] and (inaudible) stem cell transfer TMA, both potential blockbusters opportunities.

我們憑藉開創性的 C5 特許經營權保持在罕見病領域的領先地位，這將在近期至中期實現增長，我們的新型補充和超越補充藥物將有助於支持阿斯利康的長期增長目標。我們宣布 Ultomiris 將於明年年底在 85 個國家上市，並表示計劃推出和擴展心臟手術相關 [AKI] 和（聽不清）幹細胞轉移 TMA，這兩個潛在的重磅機會。

Beyond our C5 franchise, we continue to progress 2 of our oral factor D complement medicine and reported Phase III data for danicopan in PNH patients with clinically significant extravascular hemolysis, which represents 10% to 15% of the overall PNH population not presently managed with Ultomiris. Our next-generation oral Factor D, vemircopan, as launch those Phase II trials for myasthenia gravis and renal indications, and our Phase II PNH monotherapy trial is nearing completion.

除了我們的 C5 特許經營權之外，我們繼續推進我們的 2 個口服因子 D 補充藥物，並報告了 danicopan 在具有臨床顯著血管外溶血的 PNH 患者中的 III 期數據，這佔目前未使用 Ultomiris 管理的 PNH 總人口的 10% 至 15% .我們的下一代口服因子 D 維米可潘將啟動針對重症肌無力和腎臟適應症的 II 期試驗，我們的 II 期 PNH 單藥治療試驗即將完成。

Beyond Complement, related plans to initiate a Phase III program for ALXN1850, our next-generation medicine for HPP, following Phase I results. We expect ALXN1850 can more than double the addressable population of Strensiq given an expanded label and more favorable dosing profile. We also continue to advance our exciting portfolio of novel depleters for the treatment of amyloidosis, which have the potential to buy and clear fibril deposition in tissue and potentially reverse the course of the disease. Phase III trials for CAEL-101 in light chain amyloidosis are progressing, and we see significant potential for NI006 for the treatment of TTR cardiomyopathy.

除了補充，相關計劃啟動 ALXN1850 的 III 期計劃，我們的下一代 HPP 藥物，在 I 期結果之後。我們預計 ALXN1850 可以使 Strensiq 的可尋址人群增加一倍以上，因為它具有擴展的標籤和更有利的劑量分佈。我們還繼續推進我們令人興奮的用於治療澱粉樣變性的新型耗竭劑組合，這些耗竭劑有可能購買和清除組織中的原纖維沉積，並有可能逆轉疾病的進程。 CAEL-101在輕鏈澱粉樣變性中的 III 期試驗正在進行中，我們看到 NI006 治療 TTR 心肌病的巨大潛力。

Next, we continue to build bridges with AstraZeneca to maximize our commercial capabilities and operational network. And as you heard Aradhana speak to you earlier, we are delivering on our commitment at the time of acquisition, and we plan to expand our Rare Disease portfolio into 100 countries by 2030.

接下來，我們將繼續與阿斯利康建立橋樑，以最大限度地發揮我們的商業能力和運營網絡。正如您之前聽到 Aradhana 對您所說的那樣，我們正在履行我們在收購時的承諾，我們計劃到 2030 年將我們的罕見病產品組合擴展到 100 個國家。

As part of our bridges, we highlighted the opportunity to apply AstraZeneca existing genomic medicine technologies for Rare Disease and made additional progress in this effort with our proposed acquisition of LogicBio, a genomic medicine company based outside of Boston, Massachusetts.

作為我們橋樑的一部分，我們強調了將阿斯利康現有的基因組醫學技術應用於罕見病的機會，並通過我們提議收購位於馬薩諸塞州波士頓以外的基因組醫學公司 LogicBio，在這方面取得了額外的進展。

Now turning to Slide 28. This acquisition enhances our existing generic medicine capabilities, bringing in-house a team of talented researchers as well as 3 novel technologies that will help accelerate our ongoing effort, including a proprietary AAV manufacturing platform aimed to improve product yields and quality. Pending necessary regulatory currencies, we anticipate the deal to close in the coming weeks. Together with my Alexion and AstraZeneca colleagues, I look forward to welcoming the talented LogicBio team in our organization, and I am optimistic as to what we can accomplish together to advance genomic medicine for the treatment of Rare Disease.

現在轉到幻燈片 28。此次收購增強了我們現有的仿製藥能力，帶來了一支由才華橫溢的研究人員組成的內部團隊以及 3 項有助於加快我們持續努力的新技術，包括旨在提高產品產量的專有 AAV 製造平台和質量。在等待必要的監管貨幣之前，我們預計該交易將在未來幾週內完成。與我的 Alexion 和 AstraZeneca 同事一起，我期待著在我們的組織中歡迎才華橫溢的 LogicBio 團隊，我對我們可以共同完成的工作感到樂觀，以推進基因組醫學治療罕見病。

And with that, I will turn to Slide 29, and hand over to Pascal.

有了這個，我將轉到幻燈片 29，然後交給 Pascal。

Thank you, Marc. Next slide, please.

謝謝你，馬克。請下一張幻燈片。

Looking forward, our strategic priorities remain unchanged. We will continue to invest and grow our business with the aim to be at the forefront of industry -- of our industry in the years to come. Aradhana described how we are being thoughtful and disciplined with each investment that we make, driving efficiencies and investing in new technologies to make our development and our commercialization efforts faster and more impactful. I would also like to point out that we are in a fortunate position of having several high-priority medicines in development and new launches to support our industry-leading growth.

展望未來，我們的戰略重點保持不變。我們將繼續投資和發展我們的業務，目標是在未來幾年走在行業的前沿——我們行業的前沿。 Aradhana 描述了我們如何在進行每項投資時都深思熟慮和自律，提高效率並投資於新技術，以使我們的發展和商業化工作更快、更有影響力。我還想指出，我們有幸擁有幾種高優先級藥物正在開發和新推出，以支持我們行業領先的增長。

Our long-term margin ambition has not changed. And as you know, the pace of continued margin expansion is dependent on our pipeline success and also on some external factors, in particular, the evolution of currencies. Delivering value to our shareholders is very important to us.

我們的長期利潤率目標沒有改變。如您所知，利潤率持續擴張的步伐取決於我們管道的成功以及一些外部因素，特別是貨幣的演變。為我們的股東創造價值對我們來說非常重要。

Turning to our outlook for 2023. We will, of course, provide our guidance for the year with our full year results for 2022. But I would point out that we anticipate at least 18 Phase III trial readouts in the year. We also look forward to announcing brand new Phase III starts for key medicines as we strengthen our pipeline and our business outlook for the next decade and beyond.

談到我們對 2023 年的展望。當然，我們將在 2022 年全年業績中提供我們對這一年的指導。但我要指出，我們預計今年至少有 18 個 III 期試驗讀數。隨著我們加強我們的管道和未來十年及以後的業務前景，我們還期待宣布關鍵藥物的全新 III 期啟動。

Now, we'll close with Slide 31. Importantly, I've just returned from the COP27 conference, and I would like to highlight our landmark announcement as an industry. For the Sustainable Markets Initiatives Health Systems Taskforce, which for those who do not know, is a public private partnership I convened under the overall SMI umbrella, which was launched by King Charles III 2 years ago. We have collectively, as an industry, made significant commitments to tackle the climate crisis. The pride sector organizations in this coalition will have their own decarbonization targets, including our own Ambition Zero Carbon strategy.

現在，我們以幻燈片 31 結束。重要的是，我剛剛從 COP27 會議回來，我想強調我們作為一個行業的里程碑式公告。對於那些不知道的人來說，可持續市場倡議衛生系統工作組是我在 SMI 總體框架下召集的公私合作夥伴關係，該框架由查爾斯三世國王於 2 年前發起。作為一個行業，我們集體做出了應對氣候危機的重大承諾。該聯盟中的驕傲部門組織將有自己的脫碳目標，包括我們自己的“野心零碳”戰略。

However, what makes this announcement unique is the taskforce's ability to unite and drive collective action at scale, addressing emissions across our supply chains, patient care pathways and clinical trials, and setting a benchmark to inspire others. Society is increasingly looking for companies to step up and lead by example in addressing climate change, and that is what we intend to do.

然而，該公告的獨特之處在於，該工作組能夠團結一致並大規模推動集體行動，解決我們供應鏈、患者護理途徑和臨床試驗中的排放問題，並設定基準以激勵他人。社會越來越多地尋找公司在應對氣候變化方面站出來並以身作則，這就是我們打算做的事情。

Now, we'll turn back to Andy.

現在，我們將回到安迪。

Thank you, Pascal. If you turn to the next slide, please. (Operator Instructions). Let's now take the first question from the call.

謝謝你，帕斯卡。請翻到下一張幻燈片。 （操作員說明）。現在讓我們從電話中提出第一個問題。

So the first question is Simon Baker. Simon, on to you.

所以第一個問題是西蒙貝克。西蒙，給你。

One, if I may, on Oncology, but in 2 parts.

一個，如果可以的話，關於腫瘤學，但分為兩部分。

The first one is fairly quick. Dave, I wonder if you could quantify the -- any impact of stocking on the -- from the [Mali] form of Calquence in the U.S?

第一個相當快。戴夫，我想知道你是否可以量化美國 [馬里] 形式的 Calquence 對庫存的任何影響？

And then secondly, a question for both both Dave and Susan. We've seen obviously a lot of developments in the SERD space this year. Your positive data, disappointments elsewhere. If I look what consensus estimates have done over the course of the year, they've -- if anything, they've fallen rather than risen. So that may just be a lagging effect on the part of analysts. But I just wonder how your view has changed on camizestrant in light of what you've seen in terms of the data and the market opportunity in light of disappointments elsewhere?

其次，Dave 和 Susan 都有一個問題。今年我們顯然已經看到了 SERD 領域的許多發展。您的積極數據，其他地方的失望。如果我看一下共識估計在一年中所做的事情，他們已經 - 如果有的話，他們已經下降而不是上升。因此，這可能只是分析師的滯後效應。但我只是想知道，鑑於您在數據和市場機會方面看到的其他情況令人失望，您對 camizestrant 的看法有何變化？

So starting, Simon, on your first question on Calquence. What I had mentioned in the prepared remarks was about half of the consensus beat, we believe is a result of stocking in the U.S. for [MAlIATE]. Just to put a little bit more on that, u.S. demand continues to be quite strong in frontline. New patient share in CLL is now greater than 55%, and I also would like to note that I think it's important with the maleate tablet approval in the U.S., we now really address an important patient need, which is the ability to be able to combine with PPIs. And this really adds to the value proposition of Calquence more broadly.

西蒙，開始你關於 Calquence 的第一個問題。我在準備好的評論中提到的大約是共識節拍的一半，我們認為這是在美國為 [MAlIATE] 備貨的結果。只是多說一點，美國一線需求依然強勁。 CLL 中的新患者份額現在超過 55%，我還想指出，我認為馬來酸鹽片劑在美國的批准很重要，我們現在真正解決了一個重要的患者需求，即能夠與 PPI 結合。這確實更廣泛地增加了 Calquence 的價值主張。

Susan, do you want to comment on cami?

蘇珊，你想評論卡米嗎？

Yes. So we remain confident in the profile that we've got with camizestrant and also the role for a next-generation SERD in improving and becoming a backbone best-in-class endocrine therapy, particularly in the endocrine sensitive disease, which is in first-line metastatic hormone receptor positive and in the early stages of breast cancer. .

是的。因此，我們對 camizestrant 的概況以及下一代 SERD 在改善和成為一流內分泌治療的骨幹方面的作用仍然充滿信心，特別是在內分泌敏感疾病中，這是在第一-線轉移性激素受體陽性且處於乳腺癌的早期階段。 .

In order to achieve that profile, you have to have the right safety profile, which is absolutely key, and the combined ability with other medicines such as CDK4/6 inhibitors. So the profile that we have with camizestrant is one we're confident in. Be happy to discuss the data more once we share it at San Antonio Breast Cancer Conference.

為了實現這一目標，您必須擁有正確的安全性，這絕對是關鍵，以及與 CDK4/6 抑製劑等其他藥物的聯合能力。因此，我們對 camizestrant 的個人資料是我們有信心的。一旦我們在聖安東尼奧乳腺癌會議上分享這些數據，我們很高興能更多地討論這些數據。

Thanks, Susan.

謝謝，蘇珊。

Next one is Sachin at Bank of America.

下一位是美國銀行的薩欽。

Two, please. One on financial, one pipeline.

兩個，請。一個是金融，一個是管道。

Firstly, on financials. Pascal, very kindly noted pace of margin expansion will depend on pipeline and FX. Could you give us, based on what you know today, your best view of how you think margins progress? And I guess I'd frame a [comment] related to consensus, which has 500 basis points over the next 2 years and roughly half of that next year. So based on what you know today, does that look fair or not?

首先，關於財務。帕斯卡（Pascal）非常友好地指出，利潤率擴張的速度將取決於管道和外匯。根據您今天所了解的情況，您能否向我們提供您對利潤率進展的最佳看法？我想我會提出一個與共識相關的[評論]，在接下來的兩年裡有 500 個基點，明年大約有一半。所以根據你今天所知道的，這看起來公平還是不公平？

Second question is on the PD1-CTLA4 bi-specific. I wonder is if you could give some more details? You've referenced a comprehensive program, but is that next step Phase III, or do you need more Phase I? How many tumors are you debating? I'd be thinking sort of 4 to 5. And any more color on the lower dose efficacy where we had only limited data at ESMO?

第二個問題是關於 PD1-CTLA4 雙特異性的。我想知道您是否可以提供更多詳細信息？您參考了一個綜合計劃，但下一步是第三階段，還是您需要更多第一階段？你在討論多少個腫瘤？我想大概是 4 到 5。在我們在 ESMO 僅有有限數據的情況下，還有更多關於低劑量功效的顏色嗎？

Susan, do you want to start with the first question and maybe Aradhana, you could take the other one?

蘇珊，你想從第一個問題開始，也許阿拉達納，你可以回答另一個問題嗎？

So obviously, as we said at ESMO, we're continuing to look at both the 750 and 500-milligram dose levels for (inaudible). You can see that we will be looking at the discontinuation rate as well as the longer-term progression-free survival rate in those settings. And again, we're confident based on the data that we've seen that we've got a good profile. And as we develop the development plan, we'll be happy to share those -- that progress with you.

很明顯，正如我們在 ESMO 所說，我們將繼續研究 750 和 500 毫克的劑量水平（聽不清）。您可以看到，我們將關注這些環境中的停藥率以及長期無進展生存率。再一次，我們有信心根據我們看到的數據，我們有一個很好的個人資料。在我們制定發展計劃時，我們很樂意與您分享這些進展。

So your second question regarding margins. So again, our ambition relating to improving margins consistently remains very much the same. You've seen -- this year, we have continued to improve our margins, and I talked about several productivity initiatives that we have to continue to improve that.

所以你關於利潤的第二個問題。同樣，我們與提高利潤率有關的雄心始終保持不變。你已經看到 - 今年，我們繼續提高我們的利潤率，我談到了我們必須繼續改進的幾項生產力舉措。

I think looking forward, we continue to see very strong business performance across our various units. We talked about 19 approvals this quarter, and obviously, we're looking forward to some more later this year and launching all of that in 2023. We're seeing strong growth in our emerging markets business. R&D, we are committed to continuing to invest in. You've seen strong pipeline success and track record there. And then obviously, there are external factors including currency, inflation. Key variable is the -- what happens with our COVID medicines in the coming year, and then also the NRDL and VBP.

我認為展望未來，我們將繼續看到我們各個部門的強勁業務表現。我們本季度討論了 19 項批准，顯然，我們期待今年晚些時候獲得更多批准，並在 2023 年推出所有這些批准。我們看到新興市場業務的強勁增長。研發，我們致力於繼續投資。您已經看到了強大的管道成功和記錄。然後很明顯，還有外部因素，包括貨幣、通貨膨脹。關鍵變量是——來年我們的 COVID 藥物會發生什麼，然後是 NRDL 和 VBP。

So there's a lot more variables that I just laid out. So again, we won't be giving guidance for 2023 until we announce our full year results.

因此，我剛剛列出了更多變量。因此，在我們宣布全年業績之前，我們不會為 2023 年提供指導。

Thanks, Aradhana.

謝謝，阿拉達納。

If you look at Q3 and our operating margin and the improvement we achieved despite what I would call really kind of strong, really ForEx headwinds, that really reflects the strength of the underlying business. But having said that, moving forward, and Aradhana said, there's so many variables. We need to get a better sense of where those currencies go and what the outlook for the future is.

如果你看看第三季度和我們的營業利潤率以及我們取得的進步，儘管我稱之為非常強大的外匯逆風，這確實反映了基礎業務的實力。但話雖如此，繼續前進，阿拉達納說，有很多變數。我們需要更好地了解這些貨幣的去向以及未來的前景。

But certainly, our ambition remains intact at this point.

但可以肯定的是，我們的雄心在這一點上仍然完好無損。

The next one is Andy Baum at Citi.

下一位是花旗的安迪鮑姆。

Yes. A couple of questions.

是的。幾個問題。

Firstly, could you talk to the outlook for your COVID-19 monoclonal antibodies, Evusheld? On the one hand, you've got escape variants which may impact the EUA. On the other hand, I know you have next-generation monoclonals. If you could update us on timing and how you're thinking about what you intend to deliver to the market next year? That would be helpful.

首先，您能否談談您的 COVID-19 單克隆抗體的前景，Evusheld？一方面，你有可能影響 EUA 的逃生變體。另一方面，我知道你們有下一代單克隆抗體。您能否向我們介紹一下時間安排以及您對明年打算向市場提供什麼產品的想法？那會很有幫助。

And then second, Farxiga, obviously, is a cornerstone diabetes drug. But the road is running out, although you do have life cycle management strategies. I know you have a long-standing collaboration with Amgen, which doesn't have a primary care business. They recently posted data with [AMG-133] killed your (inaudible) blue agent in diabetes and in obesity. I'm just curious as whether there will be any appetite for engaging and extending that collaboration? Any thoughts there?

其次， Farxiga 顯然是一種基礎糖尿病藥物。但是，儘管您確實有生命週期管理策略，但這條路已經不多了。我知道您與沒有初級保健業務的安進（Amgen）有長期合作。他們最近發布了 [AMG-133] 在糖尿病和肥胖症中殺死你的（聽不清）藍色藥劑的數據。我只是好奇是否會有興趣參與和擴展這種合作？有什麼想法嗎？

And then finally, very quickly, and feel free to pass on this. Can you tell me why I shouldn't expect Calquence to be significantly revised onwards given near-term [NCM] guidelines? And the second, IMBRUVICA, will they have a price negotiation cut of about 65% to ['26]? Feel free to pass on those in the interest of time.

最後，很快，請隨意傳遞這個。你能告訴我為什麼我不應該期望 Calquence 會在近期 [NCM] 指導方針下進行重大修訂嗎？第二個，IMBRUVICA，到 ['26] 時，他們的價格談判是否會削減約 65%？為了時間的利益，請隨意傳遞那些。

Thank you, Andrew, and I'm so happy that Andy took the thankless task of asking everybody one question. Has not succeeded at all so far today.

謝謝你，安德魯，我很高興安迪承擔了向每個人提出一個問題的吃力不討好的任務。今天到現在都沒有成功。

Can you quickly cover the last one, Dave? Or do you want to start with this one, and if I could cover the monoclonal inhibition?

戴夫，你能快點講完最後一個嗎？或者你想從這個開始，如果我能涵蓋單克隆抑制？

Yes. So Andrew, from our perspective, as we continue to look at the performance of Calquence, we see that really, the results, whether it's from our own ELEVATE-TN studies, the ALPINE results, what we're seeing coming out at ASH, that all of this underscores our belief, and I think it's consistent with what we hear from the marketplace, that the next generation BTKis like Calquence have a differentiated and better profile than the first generation BTKi. And I think that this is what gives us confidence in our ability to continue to establish Calquence as the standard of care within this next-generation class. .

是的。所以 Andrew，從我們的角度來看，當我們繼續觀察 Calquence 的表現時，我們確實看到了結果，無論是來自我們自己的 ELEVATE-TN 研究、ALPINE 結果，還是我們在 ASH 上看到的結果，所有這些都強調了我們的信念，而且我認為這與我們從市場上聽到的一致，即像 Calquence 這樣的下一代 BTK 比第一代 BTK 具有差異化和更好的形象。我認為這讓我們有信心繼續將 Calquence 確立為下一代護理標準。 .

When I take a look at the progress that other competitors have made in places where we face head-to-head competition in the U.S. and MCL in the relapsed/refractory setting, Calquence share has held strong. The gains that (inaudible) have made have come at the expense of [brew], and we continue to see good progress being made in terms of innovations with things like the maleate tablet formation.

當我看看其他競爭對手在我們在美國面臨正面競爭和 MCL 在復發/難治環境中所取得的進展時，Calquence 的份額一直保持強勁。 （聽不清）取得的進展是以犧牲 [brew] 為代價的，我們繼續看到在馬來酸鹽片劑形成等創新方面取得了良好進展。

Thank you, Dave.

謝謝你，戴夫。

Thanks, Andy, for the question. Let me first address your first part of your question around the initial outlook. .

謝謝，安迪，這個問題。讓我首先回答你關於初步前景的問題的第一部分。 .

So I think it's important to know that (inaudible) is still playing a very important role for the immunocompromised patient. As we know, this is the only option for those patients to be protected from COVID-19, and we also know that they are under significant high risk of the hospitalization and death from COVID.

所以我認為重要的是要知道（聽不清）對於免疫功能低下的患者仍然發揮著非常重要的作用。眾所周知，這是保護這些患者免受 COVID-19 感染的唯一選擇，而且我們也知道他們面臨因 COVID 住院和死亡的高風險。

Now it is true that the new variance that we see arising can have -- can cause the decrease of the activity of Evusheld. And we obviously, together with the government's monitoring and collecting the data, both in vitro lab neutralizing data as well as real-world effectiveness data to make sure that Evusheld keeps clinical efficacy for those patients. It's very difficult to forecast the new variant outlook, and it seems that this winter will be a winter of many different variants. Some of them will be less active or some of them, Evusheld, can be less or more active. But we definitely continue to work with the regulators and governments to collect and provide the data.

現在確實，我們看到出現的新差異可能會導致 Evusheld 的活動減少。我們顯然，連同政府的監測和收集數據，包括體外實驗室中和數據以及真實世界的有效性數據，以確保 Evusheld 對這些患者保持臨床療效。新變種的前景很難預測，看來這個冬天將是一個多變種的冬天。其中一些將不那麼活躍，或者其中一些，Evusheld，可以更少或更多活躍。但我們肯定會繼續與監管機構和政府合作，收集和提供數據。

On your second question on the -- our new Evusheld 2.0 and next generation of the long-acting monoclonal antibodies, I think this really speaks to our commitment to the immunocompromised patients, and we are doing our best to accelerate the development and delivery of the new Evusheld. Currently, we are in the pre-clinical development, and we are -- we believe that we will be able to bring it to the patient at the end of the next year.

關於第二個問題——我們的新 Evusheld 2.0 和下一代長效單克隆抗體，我認為這確實體現了我們對免疫功能低下患者的承諾，我們正在盡最大努力加速開發和交付新的 Evusheld。目前，我們正處於臨床前開發階段，我們相信我們將能夠在明年年底將其帶給患者。

Thank you, Iskra.

謝謝你，火星報。

I mean, Andrew, just maybe to add, I think it's important to remember, at the end of the day, what matters is the clinical activity. And then sometimes we see reduced activity in laboratories. But in fact, in real life, what we have seen so far is continued high level of protection, especially against severe disease with this antibody. It continues to be active, and we haven't had any concerns expressed by authorities so far. And as Iskra was just explaining, those variants, they change a lot. And we see, in some countries, new variances that are very contagious, that are actually sensitive to Evusheld. So this situation can change the other way around very rapidly. So it is really hard to predict.

我的意思是，安德魯，也許要補充一點，我認為重要的是要記住，歸根結底，重要的是臨床活動。然後有時我們會看到實驗室活動減少。但事實上，在現實生活中，到目前為止，我們所看到的是持續的高水平保護，尤其是針對這種抗體的嚴重疾病。它繼續活躍，到目前為止，我們還沒有收到當局表示的任何擔憂。正如《火星報》剛剛解釋的那樣，這些變體變化很大。我們看到，在一些國家，新的變異非常具有傳染性，實際上對 Evusheld 很敏感。因此，這種情況可以非常迅速地反過來改變。所以真的很難預測。

On the Farxiga front, I mean, you're right to say that we have a strong commercial organization, and I think we're all very proud of the work the team has done around the world. And a primary care organization that has the strengths that we have is quite rare in the industry, actually. And beyond primary care, we have strengths in nephrology and cardiology and diabetology, and that positions us well to do business development activities.

在 Farxiga 方面，我的意思是，你說得對，我們擁有強大的商業組織，我認為我們都為團隊在世界各地所做的工作感到非常自豪。實際上，擁有我們所擁有的優勢的初級保健組織在業內非常罕見。除了初級保健之外，我們在腎病學、心髒病學和糖尿病學方面也有優勢，這使我們能夠很好地開展業務發展活動。

But as it relates to the specific case that you mentioned, as you can imagine, I cannot answer. The only thing I can tell you is that we certainly continue to look at potential business development opportunities that fit with our therapy areas of focus and where we could add value through our expertise, and also importantly, our global commercial network.

但由於涉及到你提到的具體案例，你可以想像，我無法回答。我唯一可以告訴您的是，我們當然會繼續尋找與我們的治療重點領域相匹配的潛在業務發展機會，以及我們可以通過我們的專業知識以及重要的是我們的全球商業網絡來增加價值的地方。

So we'll move to the next one, Tim Anderson at Wolfe.

所以我們將轉到下一位，沃爾夫的蒂姆安德森。

Enhertu in the U.S., a big quarter. Was that all demand driven, or was there some stocking in bolus? And then is it unrealistic to think that global peak sales of the molecule could surpass the Tagrisso peak at some point well into the future?

Enhertu 在美國，一個很大的季度。是所有需求驅動的，還是有一些大劑量的庫存？那麼認為該分子的全球銷售高峰可能會在未來某個時候超過 Tagrisso 的銷售高峰是不現實的嗎？

And then a second question on (inaudible). For a long time, Astra had the joint venture with Merck, the Astra-Merck joint venture. Is any potential financial liability that you face shared with Merck because of that? And if so, are the parties in dispute in any aspect of this?

然後是關於（聽不清）的第二個問題。長期以來，Astra 與默克公司有合資企業，即 Astra-Merck 合資企業。您是否因此而與默克公司分擔任何潛在的財務責任？如果是這樣，當事方在這方面是否存在爭議？

Sorry, Tim, can you repeat the second question so we make sure we have got it correctly?

抱歉，蒂姆，你能重複第二個問題，以便我們確保我們得到正確的答案嗎？

Yes. So my question is just on the PPI litigation. So you used to have the Astra-Merck joint venture. I'm wondering if there's a share

是的。所以我的問題只是關於 PPI 訴訟。所以你曾經擁有 Astra-Merck 合資企業。我想知道有沒有分享

Got it. Got it. Dave, do you want to cover the first one?

知道了。知道了。戴夫，你想覆蓋第一個嗎？

Yes. Tim, the growth that we saw in third quarter came from continuation of progress on DESTINY-Breast03, and we continue to see good inroads as we displace (inaudible) use in that second-line HER2-high population. And then I would say that the real change in velocity, if you will, of the uptake is the addition of the HER2-low DBO4 launch. .

是的。蒂姆，我們在第三季度看到的增長來自 DESTINY-Breast03 的持續進展，隨著我們在二線 HER2 高人群中取代（聽不清）使用，我們繼續看到良好的進展。然後我會說，如果你願意的話，吸收速度的真正變化是增加了 HER2-low DBO4 的發射。 .

I do think that we might have some bolus of patients coming on across multiple lines of post-chemotherapy. There is not, though, a stocking effect in there. So there may be some demand bolus that we see, and we'll have to see what the duration of therapy is for some of these patients. I would if you're a sixth line post-chemo patient that it will look different than if you're a third line, so a sum of what will need to see play out. But it is all demand-based from what we've seen, and there's still quite a few patients that are not receiving Enhertu in this post-chemo setting. So there's a lot of growth still Quite a lot, actually, still remaining.

我確實認為我們可能會有一些患者接受多條化療後的治療。但是，那裡沒有放養效應。因此，我們可能會看到一些需求量，我們必須看看其中一些患者的治療持續時間是多少。如果您是化療後的第六線患者，我會認為它看起來與您是第三線的患者不同，因此需要看到發揮作用的總和。但從我們所看到的情況來看，這一切都是基於需求的，在這種化療後的環境中，仍有相當多的患者沒有接受 Enhertu。所以還有很多增長實際上仍然有很多。

In terms of the overall outlook, I think Enhertu could be one of the largest medicines in oncology going forward. And whether or not that's bigger or less than Tagrisso, I think Tagrisso's one of the largest also. So I sort of put them all in the same category.

就整體前景而言，我認為 Enhertu 可能是未來腫瘤學領域最大的藥物之一。而且無論它是否大於或小於 Tagrisso，我認為 Tagrisso 也是最大的之一。所以我把它們都歸為同一類。

But it can be very big.

但它可能非常大。

If you look at in-market sales, right, that's -- I think Dave was talking about in market sales because, of course, we only record a little bit less than half of those sales. But it will -- and we enter this partnership assuming a good product but more modest forecast. And in fact, we are rapidly moving to an upside here that will make Enhertu a very large product in the industry.

如果您查看市場銷售，對，那是 - 我認為戴夫在談論市場銷售，因為當然，我們只記錄了不到一半的銷售額。但它會——我們假設一個好的產品但更溫和的預測進入這種夥伴關係。事實上，我們正在迅速向好的方向發展，這將使 Enhertu 成為業內非常大的產品。

Aradhana, do you want to cover the second one?

Aradhana，你想覆蓋第二個嗎？

Sure.

當然。

So relating to the Nexium liability, this was originally obviously a product that was developed through the Astra-Merck venture. And at that point, AZ kept the products and the liability, and we paid Merck a share of the profits.

因此，關於 Nexium 責任，這最初顯然是通過 Astra-Merck 合資企業開發的產品。那時，AZ 保留了產品和責任，我們向默克公司支付了一部分利潤。

Going forward and where the cases stand today, we are essentially liable for our own -- whatever happens in this litigation. We're obviously very confident in our position, and we continue to defend vigorously. As you know, already 5,000 cases have been dismissed. And the first of the pending cases will start trial early next year, and we'll see how they go one by one.

展望未來，在今天的情況下，我們基本上要為自己負責——無論這場訴訟中發生什麼。我們顯然對自己的立場非常有信心，我們會繼續大力防守。如你所知，已經有5000個案件被駁回。第一個未決案件將於明年初開庭審理，我們將逐一查看。

Thank you. Matthias, Handelsbanken.

謝謝你。馬蒂亞斯，德國銀行。

Question sort of related to an earlier question on Evusheld and its long-term projections, which concerns at least carry material expectations from. So when the company guides for double-digit growth until '25 and then industry-leading growth beyond '25, to what extent should we be thinking of pandemic-related revenue as part of those growth projections, or rather, the opposite? Does all such statements exclude for pandemic-related revenues?

問題與早期關於 Evusheld 及其長期預測的問題有關，該問題至少涉及重大預期。因此，當公司指導在 25 年前實現兩位數增長，然後在 25 年後實現行業領先增長時，我們應該在多大程度上將與大流行相關的收入視為這些增長預測的一部分，或者相反？所有這些報表是否都排除了與大流行相關的收入？

And then secondly, I know you're not going to talk about core EPS outlook for '23 here today, but consensus apparently is carrying a low single-digit R&D increase for next fiscal year. And I'm trying to reconcile that with the [19] readouts for next year. And I hope that would be appreciated.

其次，我知道你今天不會在這裡談論 23 年的核心每股收益前景，但共識顯然是下一財年的研發增長將保持低個位數。我正試圖將其與明年的 [19] 讀數相協調。我希望這將不勝感激。

Just let me just cover the first one, which really relates to statements we made in the past.

讓我只介紹第一個，它與我們過去所做的聲明真正相關。

When the first time we made those growth statements, we didn't really know what Evusheld would look like, quite frankly. So those growth projections that were made outside of the COVID franchise (inaudible). And of course, now you have to sort of adjust to some extent for this sales we've experienced in between. But fundamentally, the long-term growth doesn't depend -- doesn't rely on the COVID franchise. We hope and we believe that Evusheld and Evusheld 2.0 can be durable over the next few years. But certainly, our leading growth rate case beyond 2025 doesn't depend on it.

當我們第一次做出這些增長聲明時，坦率地說，我們真的不知道 Evusheld 會是什麼樣子。因此，那些在 COVID 特許經營權之外做出的增長預測（聽不清）。當然，現在你必須在某種程度上調整我們在這兩者之間經歷的銷售。但從根本上說，長期增長並不依賴——不依賴於 COVID 特許經營權。我們希望並且我們相信 Evusheld 和 Evusheld 2.0 能夠在未來幾年內經久耐用。但可以肯定的是，我們在 2025 年之後的領先增長率案例並不依賴於此。

The core EPS, you want to cover that question, Aradhana?

核心 EPS，你想解決這個問題嗎，阿拉達納？

So I think the question was really relating to the R&D expense that you have for 2023. So again, we will not give guidance for 2023 today. But as I mentioned, we do expect to maintain strong investment in R&D. We've shown a very strong track record, and we've said that our R&D expense will remain sort of in the low 20s percentage as a percentage of revenue. Obviously, that will be underpinned by high-quality assets that will continue to advance.

所以我認為這個問題真的與你在 2023 年的研發費用有關。所以，我們今天不會給出 2023 年的指導。但正如我所提到的，我們確實希望保持對研發的強勁投資。我們已經展示了非常強勁的業績記錄，我們已經說過，我們的研發費用佔收入的百分比將保持在 20 年代的低位。顯然，這將得到將繼續推進的優質資產的支撐。

Maybe one thing I could add to this is brings us back to our products. I mean if you look at it, Enhertu has enormous potential. I think we've just mentioned it, but we have to support it. I think that Dato-DXd is probably still underestimated. It has enormous potential, and we will, together with our partners, Daiichi Sankyo, we will really invest in it to maximize it.

也許我可以添加的一件事是讓我們回到我們的產品。我的意思是，如果你看一下，Enhertu 具有巨大的潛力。我想我們剛剛提到了它，但我們必須支持它。我認為 Dato-DXd 可能仍然被低估了。它具有巨大的潛力，我們將與我們的合作夥伴第一三共（Daiichi Sankyo）一起，真正投資於它以最大限度地發揮它。

Now we were very excited recently, as you heard from Susan, to see the results of [CRN-2] study. Camizestrant has good potential, great potential and -- but we have to invest in it, and we are doing this. And there are many more like this, we are investing in Tezspire. We are looking at our [IL-33] (inaudible), and we will also look at based on the results we see in Phase II, we'll also look at potential investing in several indications.

現在，正如您從 Susan 那裡聽到的，我們最近非常興奮地看到 [CRN-2] 研究的結果。 Camizestrant 具有良好的潛力，巨大的潛力，而且——但我們必須對其進行投資，而且我們正在這樣做。還有更多這樣的，我們正在投資 Tezspire。我們正在研究我們的 [IL-33]（聽不清），我們還將根據我們在第二階段看到的結果進行研究，我們還將研究幾個跡象的潛在投資。

So we will maximize the value of each key asset we have. They all have large potential. But of course, it will require R&D investment. So certainly, our goal is to continue investing in R&D at the same level, as we've said before, which is in the sort of low 20s.

因此，我們將最大化我們擁有的每項關鍵資產的價值。他們都有很大的潛力。但當然，這將需要研發投資。所以當然，我們的目標是繼續在相同的水平上投資研發，正如我們之前所說的那樣，它處於 20 多歲的低水平。

And by the way, maybe I should also have added that the Rare Disease early pipeline is starting to mature, and over the next 2 to 3 years, we're very excited to see the kind of products we could actually bring to Phase III and then to patients. So all of this takes us back to continued investment in R&D. There's no question.

順便說一句，也許我還應該補充一點，Rare Disease 的早期管道已經開始成熟，在接下來的 2 到 3 年內，我們很高興看到我們實際上可以將這種產品帶到 III 期和然後給患者。因此，所有這一切都讓我們回到了對研發的持續投資。沒有問題。

Mark Purcell at Morgan Stanley.

摩根士丹利的馬克·珀塞爾。

Yes. A couple for me.

是的。給我一對。

Firstly, on Dato-DXd, could you sort of help us understand the more predictive biomarker you've developed for lung cancer and implications for opportunities beyond the first and second line setting in [non-squamous] lung cancer. What's your latest thoughts in terms of development there?

首先，在 Dato-DXd 上，您能否幫助我們了解您為肺癌開發的更具預測性的生物標誌物，以及對 [非鱗狀] 肺癌一線和二線設置之外的機會的影響。您對那裡的發展有何最新想法？

And then a very quick second. In terms of camizestrant, is there an opportunity for filing an accelerated approval approach on the back of the SERENA-2 data?

然後很快。在 camizestrant 方面，是否有機會在 SERENA-2 數據的背面提交加速批准方法？

Susan?

蘇珊？

Sure.

當然。

So on Dato-DXd, the biomarker that we're looking at will be based on the expression of [Coke 2]. And as I've said before, I think it's important that you get the right immunohistochemistry assay for that and understand the [cuts], which we're looking at using computational pathology, amongst other techniques. So I think that might be important in terms of identifying the right patient population across a number of different potential indications for Dato-DXd.

所以在 Dato-DXd 上，我們正在研究的生物標誌物將基於 [Coke 2] 的表達。正如我之前所說，我認為重要的是你要為此獲得正確的免疫組織化學分析並了解我們正在使用計算病理學等技術研究的[切割]。因此，我認為這對於在 Dato-DXd 的許多不同潛在適應症中確定合適的患者群體方面可能很重要。

That being said, I think in the first TROPION-Lung01 study, we're very confident based on the data that we've already seen from the Phase I that we can beat the current standard of care in all (inaudible) patient population.

話雖如此，我認為在第一項 TROPION-Lung01 研究中，基於我們已經從第一階段看到的數據，我們非常有信心，我們可以在所有（聽不清）患者群體中超越目前的護理標準。

With regard to your second question for all SERD, again, the SERENA-2 study was designed as a randomized dose-finding study, and the setting of (inaudible) as to breast cancer isn't one where monotherapy endocrine therapy is perhaps the best opportunity to make the biggest difference for patients. Nonetheless, we're excited by the data that we've seen in the SERENA-2, look forward to sharing that at San Antonio, and we look forward to the confidence that gives us for where we think we can make the biggest difference which, as I said, is an earlier line and the early-stage setting of endocrine-sensitive breast cancer.

關於你對所有 SERD 的第二個問題，SERENA-2 研究被設計為一項隨機劑量發現研究，並且（聽不清）關於乳腺癌的環境並不是單藥內分泌治療可能是最好的為患者帶來最大改變的機會。儘管如此，我們對我們在 SERENA-2 中看到的數據感到興奮，期待在聖安東尼奧分享這些數據，我們期待在我們認為可以做出最大改變的地方給予我們信心，正如我所說，是內分泌敏感型乳腺癌的較早路線和早期設置。

Stephen Scala at Cowen.

考恩的斯蒂芬·斯卡拉。

I have one question and one follow-up.

我有一個問題和一個跟進。

First on Lynparza, should we expect a CRPC label to reflect the PROPEL population or be more narrow than that in some way?

首先在 Lynparza 上，我們應該期望 CRPC 標籤反映 PROPEL 人群還是在某種程度上比這更窄？

And second, Pascal, this is the follow-up. You've been in the industry a long time and have seen a lot of product-related litigation. Can you put the Nexium litigation in context? And how does it compare to other situations, which maybe you had less than ideal outcomes on any key legal or medical, legal or other parameters?

第二，帕斯卡，這是後續行動。您已經在該行業工作了很長時間，並且看到了很多與產品相關的訴訟。您能否將 Nexium 訴訟放在上下文中？它與其他情況相比如何，可能您在任何關鍵的法律或醫學、法律或其他參數上的結果都不理想？

Susan, do you want to take the first one?

蘇珊，你要拿第一個嗎？

Yes.

是的。

So based on the data that we shared at ASCO GU at the beginning of this year, you can see a clinically meaningful improvement in radiographic and progression-free survival in both the patients that have HRR wild-type and BRCA wild-type population, as well as within the BRCA-mutant patient population. So that clinical meaningfulness and the tolerability that's seen in combination with (inaudible), I think, supports an indication that's aligned with the patient population that was enrolled. Obviously, we -- I mean, continued discussions with regulatory authorities around the world, and we'll update you as soon as we have a finalized agreement with those regulatory authorities.

因此，根據我們今年年初在 ASCO GU 上分享的數據，您可以看到 HRR 野生型和 BRCA 野生型患者的影像學和無進展生存期都有臨床意義的改善，如以及在 BRCA 突變患者群體中。因此，我認為，結合（聽不清）所看到的臨床意義和耐受性支持與登記的患者群體一致的適應症。顯然，我們 - 我的意思是，繼續與世界各地的監管機構進行討論，一旦我們與這些監管機構達成最終協議，我們將立即通知您。

Stephen. First of all, let me thank you for reminding me of my advanced age. And as address to your question, yes, I have in my long career, I've seen quite a number of those cases. And of course, we take every case very seriously.

斯蒂芬。首先，讓我感謝你讓我想起了我的高齡。作為對您問題的回答，是的，在我漫長的職業生涯中，我見過很多這樣的案例。當然，我們非常重視每一個案例。

Having said that, here, we believe we really have a strong case. Kidney disease is really so much multifactorial and influenced by so many circumstances, of course, hypertension, diabetes, et cetera. And there is clearly no proven link between Nexium and kidney disease. So we believe we definitely can manage this one in a number -- a few thousands of cases have already been dismissed.

話雖如此，在這裡，我們相信我們確實有一個強有力的案例。腎臟疾病真的是多因素的，受很多情況的影響，當然，高血壓、糖尿病等等。顯然，Nexium 與腎臟疾病之間沒有任何經證實的聯繫。因此，我們相信我們絕對可以在很多方面處理這個問題——數千個案件已經被駁回。

Having said that, of course, you always have to be prudent, and you never know what happens with those cases. But I would say, overall, it's probably at the lower end of any case I have seen in the past in this area.

話雖如此，當然，您始終必須謹慎行事，並且您永遠不知道這些案件會發生什麼。但我想說，總的來說，這可能是我過去在該領域看到的任何案例的低端。

Anything, Aradhana, you wanted to add? No.

有什麼，阿拉達納，你想補充嗎？不。

So James Gordon, JPMorgan.

所以摩根大通的詹姆斯·戈登。

Two questions, one financial, one pipeline.

兩個問題，一個財務，一個管道。

The financial question was just about the implied sequential forwarding revenues and profitability in Q4. And the question is, how much of a headwind do you think we could see from booking in advance incremental discounting in China on the NRDL renegotiation or -- algorithm adjustments were referred to. Is that something that would be a significant headwind in Q4 that we need to think about for our revenue forecast and profitability?

財務問題只是關於第四季度隱含的連續轉發收入和盈利能力。問題是，您認為我們可以從中國的 NRDL 重新談判或算法調整中提前預訂增量折扣中看到多大的阻力。對於我們的收入預測和盈利能力，這是否會在第四季度成為我們需要考慮的重大逆風？

And the second question was about pipeline and EGFR lung cancer ADCs. So you announced a new ADC592, which is wholly owned by Astra, and that targets EGFR and [cMET]. So is the idea that you would develop this for people who've got EGFR lung cancer in terms of going from an ADC approach? Or could you also develop that Dato-DXd plus (inaudible)? Would you do them in parallel or just one? And could we read this new ADC approach as endorsing the idea that it does make sense to go after cMET upfront in EGFR lung cancer w hich J&J is doing? Or is this more of a backup line if cMET doesn't look like a good thing to target upfront?

第二個問題是關於管道和 EGFR 肺癌 ADC 的。所以你們宣布了一種新的 ADC592，它由 Astra 全資擁有，針對 EGFR 和 [cMET]。那麼，從 ADC 方法的角度來看，您是否會為患有 EGFR 肺癌的人開發這個？或者您是否也可以開發 Dato-DXd plus（聽不清）？你會同時做它們還是只做一個？我們是否可以將這種新的 ADC 方法解讀為支持強生公司正在做的 EGFR 肺癌中預先研究 cMET 確實有意義的想法？或者，如果 cMET 看起來不像是預先定位的好東西，這是否更像是一條備用線路？

Two good questions. Aradhana, do you want to take the first one?

兩個好問題。 Aradhana，你想拿第一個嗎？

Sure. Yes. So obviously, we have updated our guidance the full year. And given our third quarter results, I think you can extrapolate where the range would be for the fourth quarter. We've also said that the higher end of that range is very much dependent on a couple of the factors that we mentioned, the delivery of Evusheld, which again, is variable. We're waiting for the approval of PROPEL both in the U.S. and Europe, and that would trigger certain milestones, as you know, as part of our collaboration. And then yes, there is expected some impact from the VBP and NRDL, and we'll know by end of this month where the pricing falls for -- as part of those agreements, and therefore, what the stock compensation impact will be in the fourth quarter.

當然。是的。很明顯，我們已經更新了全年的指導。鑑於我們第三季度的業績，我認為您可以推斷出第四季度的範圍。我們還說過，該範圍的高端在很大程度上取決於我們提到的幾個因素，即 Evusheld 的交付，這又是可變的。我們正在等待 PROPEL 在美國和歐洲的批准，這將觸發某些里程碑，如您所知，作為我們合作的一部分。然後是的，預計 VBP 和 NRDL 會產生一些影響，我們將在本月底知道定價落在哪裡——作為這些協議的一部分，因此，股票補償的影響將在第四季度。

So I think we've given you enough for you to be able to triangulate that. Susan?

所以我認為我們已經給了你足夠的資源讓你能夠對其進行三角測量。蘇珊？

Yes, sure.

是的，當然。

So just in terms of the potential for Tagrisso combinations. Obviously, the FLAURA-2 study, which we anticipate reading out, will give us the answer about the combination benefit of a chemotherapy plus an EGFR inhibitor in the first line. And based on the [OPL] data that we presented at ASCO, we're confident about the potential product we've got there.

所以就 Tagrisso 組合的潛力而言。顯然，我們預計會宣讀的 FLAURA-2 研究將為我們提供關於化療加 EGFR 抑製劑在一線的聯合益處的答案。根據我們在 ASCO 上展示的 [OPL] 數據，我們對我們已經獲得的潛在產品充滿信心。

We're also exploring combinations with Dato-DXd in the ORCHARD study with Tagrisso. And if that looks promising, there is a potential to go into the first line. And obviously, that's a nearer-term potential than our AZD9592, where we just filed the IND and anticipate starting Phase I later this year or early next year.

我們還在與 Tagrisso 的 ORCHARD 研究中探索與 Dato-DXd 的組合。如果這看起來很有希望，那麼就有可能進入第一線。顯然，這比我們的 AZD9592 具有更近期的潛力，我們剛剛提交了 IND 並預計在今年晚些時候或明年初開始第一階段。

I think in terms of answering your question about the place for a bi-specific EGFR MET, obviously, what you're doing is a naked antibody that's designed to overcome resistance to EGFR signal inhibition. In that setting, you're looking at MET amplification, which is a subset and a small subset of first-line EGFR mutant lung cancer. In this case, what we're looking at is the co-expression of EGFR and MET as a hook on the surface to deliver the antibody drug conjugate, so it's a different mechanism in that regard. In that setting, what you're looking for is that co-expression of MET and EGFR, which is more common not just in EGFR mutant lung cancer, but also across EGFR wild-type and also in colorectal cancer and other settings. So I think the potential development plan for AZD9592 is much wider than just EGFR mutant lung cancer.

我認為就回答你關於雙特異性 EGFR MET 的位置的問題而言，顯然，你正在做的是一種裸抗體，旨在克服對 EGFR 信號抑制的抗性。在這種情況下，您正在研究 MET 擴增，這是一線 EGFR 突變肺癌的一個子集和一小部分。在這種情況下，我們正在研究的是 EGFR 和 MET 作為表面上的鉤子的共表達以遞送抗體藥物偶聯物，因此在這方面它是一種不同的機制。在這種情況下，您正在尋找的是 MET 和 EGFR 的共表達，這不僅在 EGFR 突變肺癌中更常見，而且在 EGFR 野生型以及結腸直腸癌和其他環境中也很常見。所以我認為AZD9592的潛在開發計劃遠不止是EGFR突變肺癌。

Yes. It goes beyond lung cancer for sure. That's really a big opportunity potentially. .

是的。它肯定超越了肺癌。這確實是一個潛在的巨大機會。 .

Next one is Richard Parkes at Exane.

下一位是 Exane 的 Richard Parkes。

First one, I just wanted to push through in a little bit more on the camizestrant data ahead of the presentation. What we've seen in -- with other compounds is that the benefits in that setting have been almost solely driven by benefit in patients with [ESL-1] mutations. And I just wondered whether you've seen the same thing in SERENA-2, or have you seen broader activity? So whether you could talk about that consistency?

第一個，我只是想在演示之前多介紹一點關於 camizestrant 的數據。我們在其他化合物中看到的是，這種情況下的益處幾乎完全是由 [ESL-1] 突變患者的益處驅動的。我只是想知道您是否在 SERENA-2 中看到過同樣的事情，或者您是否看到過更廣泛的活動？那麼你是否可以談論這種一致性？

Then secondly, just on margin progression in 2023. You talked about FX being an uncertainty, so it sounds like that could be a drag to margins in 2023. I wonder if you could quantify what that would look like based on current spot rates? And then just on margins, also, you have an ongoing operational efficiency program, which I think you said would deliver over $1 billion in savings. I just wonder how much that will benefit 2023 to enable reinvestment?

其次，就 2023 年的保證金進展而言。您談到外匯是一種不確定性，因此聽起來這可能會拖累 2023 年的保證金。我想知道您是否可以根據當前的即期匯率來量化這會是什麼樣子？然後就利潤而言，你還有一個持續的運營效率計劃，我認為你說這將節省超過 10 億美元。我只是想知道 2023 年對實現再投資有多大好處？

Do you want to take the first one?

你想拿第一個嗎？

Yes. So as we've announced, the camizestrant study, SERENA-2, was positive in the overall patient population. Obviously, I can't share all of the details ahead of the San Antonio Breast Cancer Conference, but you'll note that SERENA-2 is a smaller size study than some of the other studies that we recently read out. .

是的。因此，正如我們宣布的那樣，camizestrant 研究 SERENA-2 在整個患者群體中是陽性的。顯然，我無法在聖安東尼奧乳腺癌會議之前分享所有細節，但您會注意到與我們最近宣讀的其他一些研究相比，SERENA-2 的研究規模較小。 .

So again, I look forward to sort of sharing that in the subdivisions, but we're confident that the role of this is not just in the ESR1 mutant patients, but also in the endocrine-sensitive patient population beyond ESR mutated patients.

所以再一次，我期待在細分中分享這一點，但我們相信這不僅在 ESR1 突變患者中起作用，而且在 ESR 突變患者之外的內分泌敏感患者群體中也起作用。

I mean, Richard, the FX is definitely a headwind. I mean, in terms of this year. We have, of course, a hedge if you want, because we have costs in pounds and in [krona], in particular, and other currencies, and that helps us a little bit. But the strength of the dollar is definitely this year a negative on our profitability. And that's why I mentioned before that to increase our operating margin, as you saw in the context of this negative headwind, FX headwind, is really a strong reflection of the underlying strength of the -- of our company, of our business.

我的意思是，理查德，FX 絕對是逆風。我的意思是，就今年而言。如果你願意，我們當然有對沖，因為我們有以英鎊和 [克朗] 為單位的成本，特別是其他貨幣，這對我們有一點幫助。但今年美元的強勢肯定對我們的盈利能力產生負面影響。這就是為什麼我之前提到要增加我們的營業利潤率，正如你在這種負面逆風的背景下看到的，外匯逆風確實強烈反映了我們公司和我們業務的潛在實力。

As it relates to next year, I'll ask Aradhana to comment.

由於它與明年有關，我會請 Aradhana 發表評論。

Yes. Again, we're not -- we give some sensitivity analysis relating to what FX could do this year based on the latest rates that we have. I think the general expectation is that the dollar will remain strong in 2023. So I think you could -- Again, we're not providing sensitivity for 2023, which we will do in the beginning of next year, but I think it would be fair to assume a similar impact from an FX standpoint going into next year. .

是的。同樣，我們不是——我們根據我們擁有的最新匯率對今年外匯市場的表現進行了一些敏感性分析。我認為總體預期是美元將在 2023 年保持強勢。所以我認為你可以——再說一次，我們不會提供 2023 年的敏感性，我們將在明年年初這樣做，但我認為它會是從外彙的角度來看，明年會產生類似的影響是公平的。 .

Relating to your question on the efficiency improvement which, by the way, also included the cities that we expect, and we're continuing to drive with the Alexion integration. We remain very much on track on that, and we are obviously including that as part of the drive to continuous margin improvement and reinvesting that efficiency into the business. So that is very much part of our continued improvement in margins.

關於您關於效率提高的問題，順便說一下，其中還包括我們期望的城市，我們將繼續推動與 Alexion 的整合。我們在這方面仍然非常順利，我們顯然將其作為持續提高利潤率並將這種效率再投資於業務的一部分。因此，這在很大程度上是我們持續提高利潤率的一部分。

Eric Le Barrigaud at Stifel.

Stifel 的 Eric Le Barrigaud。

Pascal. One question and one short on financials.

帕斯卡。一個問題，一個金融問題。

The question is on RNA, on respiratory enology. For a medium term out, we have many push and pull here on [Symbicort], (inaudible) and maybe [EUI] dropping off in terms of new indication for Fasenra. And on the other side, Tezspire growing and PT027 coming. And so could you get a sense of over the next 3, 4 years, how all this will balance out and if we may see just flattening sales slightly decreasing, or if there is an opportunity to remain into the positive treasury for this franchise overall?

問題是關於 RNA，關於呼吸系統學。從中期來看，我們對 [Symbicort] 有很多推拉，（聽不清），也許 [EUI] 在 Fasenra 的新適應症方面有所下降。另一方面，Tezspire 正在成長，PT027 即將到來。那麼，您能否了解在接下來的 3、4 年內，這一切將如何平衡？我們是否會看到銷售量略有下降，或者是否有機會繼續為這個特許經營權帶來積極的資金？

And the small short question on tax rate, maybe on the financial, we saw drop in tax rate for Q3. How much does that say that we're going to be at the low end of the guidance for the year? And maybe for the following years, whether we should stay around '22 level?

關於稅率的小短問題，也許是在財務上，我們看到第三季度的稅率下降。這多少說明我們將處於今年指導的低端？也許在接下來的幾年裡，我們是否應該保持在 22 年的水平？

Great question.

好問題。

I mean, Ruud, do you want to take the first one? And maybe then Mene could also sort of talk a little bit about our pipeline, because it gives you a sense of the long-term potential of this franchise.

我的意思是，路德，你想拿第一個嗎？也許梅內也可以稍微談談我們的管道，因為它讓你了解這支球隊的長期潛力。

Yes, absolutely.

是的，一點沒錯。

So first of all, we are quite pleased with the current performance of our new portfolio of products, Breztri, Fasenra and Tezspire. And we need to realize that all those products have clear life cycle opportunities. The growth of all those products is already quite impressive and especially the U.S. launch of Tezspire is very hopeful. But by doing a study with Breztri in asthma, we are doing a study with Fasenra in COPD, and there are multiple other life cycle management initiatives ongoing in order to further expand the indications for Tezspire. So of all the therapeutic areas, I feel extremely comfortable that the R&I portfolio will grow, see very strong growth.

因此，首先，我們對我們的新產品組合 Breztri、Fasenra 和 Tezspire 的當前表現感到非常滿意。我們需要意識到所有這些產品都有明確的生命週期機會。所有這些產品的增長已經相當可觀，尤其是 Tezspire 在美國的推出非常有希望。但是通過與 Breztri 在哮喘方面的研究，我們正在與 Fasenra 在 COPD 方面進行研究，並且還有多個其他生命週期管理計劃正在進行中，以進一步擴大 Tezspire 的適應症。因此，在所有治療領域中，我對 R&I 投資組合的增長感到非常滿意，看到非常強勁的增長。

At the moment, we have digested the patent loss of [Symbicort] and the ongoing loss of (inaudible) in China, but we are very, very positive about the outlook of our respiratory portfolio.

目前，我們已經消化了 [Symbicort] 的專利損失和在中國（聽不清）的持續損失，但我們對呼吸系統產品組合的前景非常非常樂觀。

Mene?

梅內？

Yes. And just to add, the molecules that you have mentioned, we've got [tozarakumab] or anti-L33 that's in late-stage development for COPD, but also be moving forward in asthma and acute respiratory failure as well. We have our inhaled biologics, which are moving. We have an oral flap, which is really interesting. And I think when you look at the wealth of data, I think we're very well positioned, not just with the molecules that we have today but also the molecular (inaudible). PD27 as well, the [adcom] yesterday was something that we view as positive. We had a good [adcom], and look forward to talking to the regulators about the populations that we will treat as we move forward.

是的。補充一下，你提到的分子，我們有 [tozarakumab] 或抗 L33，它們正處於 COPD 的後期開發階段，但也在哮喘和急性呼吸衰竭方面取得進展。我們有吸入的生物製劑，它們正在移動。我們有一個口瓣，這真的很有趣。而且我認為，當您查看大量數據時，我認為我們的定位非常好，不僅是我們今天擁有的分子，還有分子（聽不清）。 PD27 也是如此，我們認為昨天的 [adcom] 是積極的。我們有一個很好的 [adcom]，並期待與監管機構討論我們將在前進過程中對待的人群。

It's important with PD27, by the way, to -- remember, this is the first time something like this is recommended in the United States. It's a big -- a big change, and the potential is there. But as you heard from Ruud, I mean, there are ups and downs, of course, here. PD27, Breztri. Still Fasenra, Tezspire will drive growth, but on the other hand, (inaudible) is affected, (inaudible) is declining. .

順便說一句，對於 PD27，重要的是——記住，這是第一次在美國推薦這樣的東西。這是一個很大的變化，而且潛力是存在的。但正如你從 Ruud 那裡聽到的，我的意思是，當然，這裡有起有落。 PD27，布雷茲特里。仍然是 Fasenra，Tezspire 將推動增長，但另一方面，（聽不清）受到影響，（聽不清）正在下降。 .

So over the next few years, I think it's fair to expect that this franchise will not grow over the near term as much as the oncology.

因此，在接下來的幾年裡，我認為可以公平地預期這個專營權在短期內不會像腫瘤學那樣增長。

But it gives me a chance to make a point here, which I often internally make with people. I like cycling, and when you cycle, you know that if you're at the back of the pack, you consume 30%, 40% less energy. And a few years ago, Oncology was at the back of the pack. And today, Oncology is the front of the pack. And we are a business where we basically rotate and the growth will come from different franchises at a different period of times. And that's the strength of our company, not only the geographical footprint. China drove our growth over the last few years. In the last couple of years, it's going through its own patent transition, it will grow again. In the meantime, Europe, U.S., Japan are growing quite a lot. Oncology is growing. Respiratory a bit less, but Respiratory was growing a lot before. It will grow again. We have a strong pipeline. And that's really what we have to offer.

但這讓我有機會在這裡提出一個觀點，我經常在內部與人們提出這一點。我喜歡騎自行車，當你騎自行車時，你知道如果你在背包後面，你消耗的能量會減少 30%，40%。幾年前，腫瘤學處於落後地位。而今天，腫瘤學是最前沿的。我們是一個基本上輪換的企業，增長將來自不同時期的不同特許經營權。這就是我們公司的優勢，而不僅僅是地理足跡。過去幾年，中國推動了我們的增長。在過去的幾年裡，它正在經歷自己的專利過渡，它將再次增長。與此同時，歐洲、美國、日本正在大幅增長。腫瘤學正在發展。呼吸量少了一點，但呼吸量以前增長了很多。它會再次增長。我們有一個強大的管道。這就是我們必須提供的。

This diversity of geographies and diversity of products and portfolio, which gives a certain stability and predictability to the overall company. And of course, now we are not a company that is in specialty care in the U.S. with very, very high operating margins. We are targeting an improvement in operating margin, but what we have to offer is top line leading growth rates and also a certain stability of our company.

這種地域的多樣性以及產品和組合的多樣性，為整個公司提供了一定的穩定性和可預測性。當然，現在我們不是一家在美國從事專業護理業務的公司，營業利潤率非常非常高。我們的目標是提高營業利潤率，但我們必須提供的是領先的增長率以及我們公司的一定穩定性。

On the tax rate, Aradhana?

關於稅率，阿拉達納？

Yes. So just to clarify, we haven't dropped our tax rate. Again, tax is something that is really hard to pin down quarter-on-quarter. We have maintained sort of our guidance for the full year. And the quarter-on-quarter variability happens depending on the geographic mix, the business mix, the progression of certain tax audits, the carryover from prior periods and changes in tax laws, et cetera. So I don't think you should read too much into that for the full year.

是的。所以澄清一下，我們沒有降低稅率。同樣，稅收確實很難按季度確定。我們全年保持一定的指導。季度環比的變化取決於地理組合、業務組合、某些稅務審計的進展、前期結轉和稅法的變化等。所以我認為你不應該在全年閱讀太多。

As it relates to going forward, Again, in the U.K., you realize that we do have an expected tax increase. At the same time, we manage our tax rate for the long term, and we are continuously doing business planning and tax planning to manage the tax rate in the best possible manner. So that's an exercise that we continuously undertake.

由於它與前進有關，再次，在英國，您意識到我們確實有預期的增稅。同時，我們長期管理我們的稅率，我們不斷地進行業務規劃和稅收籌劃，以盡可能最好的方式管理稅率。所以這是我們不斷進行的練習。

Michael Leuchten, UBS.

瑞銀的邁克爾·勒赫滕。

Pascal. Just wanted to go back to LATIFY, as Susan mentioned it. I wondered if you could comment on how to think about that in the context of Lung01 and Lung07? There is a way to think about the ADCs in terms of cumulated toxicities over time, but it looks like you're looking at the potential IO resistance in a different way in the LATIFY trial. So just wondering if I'm over interpreting that or not?

帕斯卡。正如蘇珊所說，只是想回到 LATIFY。我想知道您是否可以評論一下如何在 Lung01 和 Lung07 的背景下思考這個問題？有一種方法可以根據隨時間累積的毒性來考慮 ADC，但看起來您在 LATIFY 試驗中以不同的方式看待潛在的 IO 阻力。所以只是想知道我是否過度解釋了這一點？

I just want to make sure that I understand your question correctly. So the LATIFY study is designed as a randomized comparison versus second-line [doxytaxyl], look at the combination of [selasertib ] and [evolumab], and it does include potential to overcome resistance to IO therapy in patients who've progressed on a prior IO-based regimen in the first-line setting.

我只是想確保我正確理解了您的問題。因此，LATIFY 研究被設計為與二線 [doxytaxyl] 的隨機比較，觀察 [selasertib ] 和 [evolumab] 的組合，它確實包括克服對 IO 治療耐藥的潛力一線環境中的先前基於 IO 的方案。

Would not create a potential conflict in where you think that could fit long term in terms of sequencing over time? That's what I was asking.

不會在您認為長期適合隨時間排序的地方產生潛在衝突嗎？這就是我要問的。

Right, okay.

對，好吧。

So I think, first of all, there are lots of opportunities within lung cancer and options that patients are going to want to have. There's also an awful lot of patients that are going to have progressed after prior checkpoint inhibition not just in lung cancer, but in other settings. So I just see this as one of the options that we can offer to patients in that second-line setting.

所以我認為，首先，肺癌中有很多機會和患者想要擁有的選擇。還有很多患者在之前的檢查點抑制後會出現進展，不僅是肺癌，還有其他情況。因此，我只是將其視為我們可以在二線環境中為患者提供的選擇之一。

And obviously, our ambition for data is to move that into the earlier lines of lung cancer. So I don't see it in long term as a conflict, but it's just a range of options that we're going to have for patients in lung cancer.

顯然，我們對數據的雄心是將其轉移到肺癌的早期階段。所以從長遠來看，我不認為這是一場衝突，但這只是我們將為肺癌患者提供的一系列選擇。

Jo Walton.

喬沃爾頓。

Two quick ones, please.

快來兩份吧。

For Aradhana, I wonder if you could tell us about how you think about gross margin going forward? You outlined that you were looking at your footprint and you were really looking at the -- at how to optimize that. How should we think in terms of potential improvement? You're already at over 80% gross margin. What could that get to in the future?

對於 Aradhana，我想知道您能否告訴我們您對未來毛利率的看法？您概述了您正在查看您的足跡，並且您確實在查看 - 在如何優化它。我們應該如何看待潛在的改進？您的毛利率已經超過 80%。將來能做什麼？

And the second question on Tagrisso, and we've all been very excited about the opportunity to move into adjuvant. It hasn't really sort of picked up yet in the sense of patients taking it. I wonder if you could give us an update on levels of awareness in the adjuvant market and the degree to which Tagrisso sales are growing there?

關於 Tagrisso 的第二個問題，我們都對有機會進入輔助崗位感到非常興奮。從患者服用它的意義上講，它還沒有真正恢復。我想知道您能否向我們介紹一下佐劑市場的意識水平以及泰瑞沙的銷售增長程度？

Do you want to take the

你想採取

Sure.

當然。

So to address your question relating to gross margins going forward and looking long term. Again, we remain committed to improving our gross margins, but I think 80%-ish is a pretty good gross margin in our industry.

因此，為了解決您關於未來毛利率和長期展望的問題。同樣，我們仍然致力於提高我們的毛利率，但我認為 80% 左右在我們的行業中是一個相當不錯的毛利率。

Now there are, again, a lot of variables that will determine what that long term looks like. The first and the most important one is the mix of our products. And that depends obviously on price which, again, is different in Oncology and Rare Diseases versus in BioPharma. It's different, for example, in China versus other geographies, et cetera. Secondly, we are constantly working on improving efficiencies and our operating, our manufacturing, et cetera, to make sure we drive efficiencies there. Thirdly, it depends very much on the costs that we get our product for the APIs, the raw materials, all of that has a direct bearing, and that's where we are seeing some impact of inflation that we continue to managed through long-term contracts and procurement activity. And then fourthly, it depends also on the mix of collaboration revenue.

現在，再次有很多變量將決定長期的樣子。第一個也是最重要的一個是我們產品的組合。這顯然取決於價格，在腫瘤學和罕見病領域與生物製藥領域又是不同的。它是不同的，例如，在中國與其他地區等等。其次，我們一直致力於提高效率和我們的運營、製造等，以確保我們在那裡提高效率。第三，這在很大程度上取決於我們獲得 API 產品的成本、原材料，所有這些都有直接影響，這就是我們看到通脹影響的地方，我們將繼續通過長期合同進行管理和採購活動。第四，它還取決於協作收入的組合。

So when you look at gross margin as a percentage, you have to be careful a little bit because as we derive more revenues from the collaboration line item, that actually is reflective of the gross margins of those products. So I think there are, again, many variables, and we continue to drive on all of them.

因此，當您將毛利率視為百分比時，您必須小心一點，因為隨著我們從合作項目中獲得更多收入，這實際上反映了這些產品的毛利率。所以我認為還有很多變數，我們將繼續推動所有這些變數。

Dave?

戴夫？

Joe. On Tagrisso, we've seen on a constant exchange rate basis, continued sequential growth on the brand and the duration of therapy from FLAURA had one of the drivers of that. But our progress on [ADORA] has also been a contributor. Now it's been a much longer educational process than what we were able to do in metastatic, and I think in large part, it's because we're really trying to change behaviors. Just if I refer back to where we were 18, 24 months ago, there's a lot of patients who are not getting treated with adjuvant therapy at all in the lung cancer setting. There's a belief that surgery alone is sufficient. We've been effectively changing that and making good inroads against that, along with also ensuring that patients that are undergoing surgery in the early stages of disease are referred to multidisciplinary teams and medical oncologists so that they can receive therapy. So we've been making good progress against it, but it's a slower process that will, I know, ultimately pay off in terms of patient outcomes and in terms of duration of therapy, and we also continue to work on improving screening efforts that more patients can be identified on the front end. And again, this is something that takes time and effort.

喬。在 Tagrisso 上，我們看到在恆定匯率基礎上，品牌的持續連續增長以及 FLAURA 的治療持續時間是其中的驅動因素之一。但我們在 [ADORA] 上的進展也是一個貢獻者。現在，這是一個比我們在轉移性癌症中能夠做到的教育過程更長的教育過程，我認為在很大程度上，這是因為我們真的在努力改變行為。如果我回顧一下我們 18、24 個月前的情況，有很多患者在肺癌環境中根本沒有接受輔助治療。有一種觀點認為，僅手術就足夠了。我們一直在有效地改變這一點，並在此方面取得良好進展，同時確保將在疾病早期接受手術的患者轉診給多學科團隊和醫學腫瘤學家，以便他們接受治療。所以我們在對抗它方面取得了很好的進展，但這是一個較慢的過程，我知道，最終會在患者結果和治療持續時間方面得到回報，我們還將繼續努力改進篩查工作可以在前端識別患者。再說一次，這需要時間和精力。

And the last thing I will note that we're happy about is that we do also now have the adjuvant approval in Japan, which gives us another market to begin moving against this objective of using it as a growth driver.

我要指出的最後一件令我們高興的是，我們現在在日本也獲得了佐劑批准，這為我們提供了另一個市場，開始反對將其用作增長動力的目標。

The biggest issue is really screening and diagnosing patients early in lung cancer, which is the big problem compared to breast cancer, for instance.

最大的問題實際上是早期篩查和診斷肺癌患者，例如，與乳腺癌相比，這是一個大問題。

Emmanuel Papadakis, Deutsche Bank.

德意志銀行的伊曼紐爾·帕帕達基斯。

Perhaps I'll start with the follow-up (inaudible). Was mentioned several times, Susan, that you thought this have indicated the potential in earlier lines, and I assume you're referring to adjuvant as part of that. Excuse me, but you've yet, I believe, to initiate an adjuvant study. Perhaps you could give us an update on your plans there and whether this makes it likely you'll proceed in a broad all-comers adjuvant population?

也許我會從後續行動開始（聽不清）。蘇珊，多次提到你認為這表明了前面幾行中的潛力，我想你指的是佐劑作為其中的一部分。對不起，但我相信你還沒有開始輔助研究。也許您可以向我們提供有關您在那裡的計劃的最新信息，以及這是否使您有可能在廣泛的所有輔助人群中繼續進行？

And then perhaps on (inaudible), good quarter. Perhaps you could just give us an update on how the MG launch is going, sources of patients where you are in terms of converting Soliris share where you think you are in terms of new starts? And if you'd be happy to provide an opinion, I think we'd love to hear your perspective on the competitive implications of the recent factor (inaudible) and PNH as well?

然後也許在（聽不清），好季度。也許您可以向我們提供有關 MG 發布進展情況的最新信息，您在轉換 Soliris 方面的患者來源以及您認為您在新開始方面的情況？如果您願意提供意見，我想我們很想听聽您對最近因素（聽不清）和 PNH 的競爭影響的看法？

Marc, do you want to start with the last question first?

馬克，你想先從最後一個問題開始嗎？

Yes, so let me provide some comments on the Ultomiris progression. As you mentioned, very strong production in the quarter, plus 47%. Regarding the launch of -- in the U.S., I suppose you referred to the U.S., but we have also launched in other territories. In the U.S., the progression in myasthenia gravis is quite good, both on the front of the conversion from Soliris. So it is developing as we had expected, but we're also very pleased with the progress we make in (inaudible) patients, naive to C5 patients, so we are -- it is progressing as we expected.

是的，所以讓我提供一些關於 Ultomiris 進展的評論。正如你所提到的，本季度的產量非常強勁，增長了 47%。關於在美國推出——我想你是指美國，但我們也在其他地區推出。在美國，重症肌無力的進展非常好，無論是在從 Soliris 轉換之前。所以它正在按我們的預期發展，但我們也對我們在（聽不清）患者中取得的進展感到非常滿意，對 C5 患者很天真，所以我們 - 它正在按我們預期的那樣進展。

If we compare the compare, let's say, the start of 2022 and where we are now, we have progressed substantially in the number of patients in myasthenia gravis, and we only launched Ultomiris in May of 2022. So good progression on the conversion and on the patients.

如果我們比較比較，比如說，2022 年初和我們現在的情況，我們在重症肌無力患者的數量上取得了長足的進步，而且我們在 2022 年 5 月才推出了 Ultomiris。轉換和之後的進展非常好患者。

Regarding the Factor B, we have seen the announcement of Factor B, and we are looking forward to seeing the presentation that will take place imminently now. We are very interested in the results. On our side, we also do a lot of progress on our overall complement inhibitors. And we have successful Phase III on (inaudible) an add-on in the same patient population, which is patient we develop EV edge on C5 therapy. And we have seen very -- we have announced our results, they are very good. We have also a Phase II study in PNH on the second factor D that we are progressing. And we have also other indications, myasthenia gravis as well as renal indications.

關於Factor B，我們已經看到了Factor B 的公告，我們期待看到即將進行的演示。我們對結果非常感興趣。在我們這邊，我們在整體補體抑製劑方面也取得了很大進展。我們在相同的患者群體中成功地進行了第三階段的（聽不清）附加治療，這是我們在 C5 治療上開發 EV 優勢的患者。我們已經看到非常 - 我們已經宣布了我們的結果，它們非常好。我們還在 PNH 進行了關於我們正在進行的第二個因素 D 的 II 期研究。我們還有其他適應症，重症肌無力以及腎臟適應症。

So we we've been very happy to have first-in-class on Factor D, and we are now developing Factor D at clinical stage as a oral treatment in the complement cascade.

因此，我們很高興在因子 D 方面處於一流水平，我們現在正在臨床階段開發因子 D，作為補體級聯的口服治療。

Marc. Susan?

馬克。蘇珊？

Yes. So do you think the profile of camizestrant is one that supports its use in the early stages? Obviously, as you've seen from the adjuvant studies with [EDK4/6] inhibitors, the design of the patient population in the adjuvant setting requires careful balancing of the risks, patients that are high enough risk. So there are -- there's an unmet need and minimizing inclusion of patients unlikely to benefit. So again, we're confident about the profile that we've got with camizestrant. We are moving ahead with the development of this program broadly in the indications where you would expect it to have efficacy.

是的。那麼您認為 camizestrant 的概況是否支持其在早期階段的使用？顯然，正如您從 [EDK4/6] 抑製劑的輔助研究中看到的那樣，輔助環境中患者群體的設計需要仔細平衡風險，即風險足夠高的患者。所以有 - 存在未滿足的需求，並且最大限度地減少了不太可能受益的患者。因此，我們再次對 camizestrant 的個人資料充滿信心。我們正在廣泛地推進該程序的開發，以適應您期望它具有功效的適應症。

Maybe let me just add on this that I said earlier, we have 15 NMEs in Phase III, and we are going to develop each of those products to their full potential. So with camizestrant, dcamera I guess you can see what I mean with that. But that, again, takes us back to have to continue our investment in R&D, and we'll keep R&D spend at the low 20s as a percentage of our revenue because we have so many huge opportunities that we can unlock.

也許讓我補充一下我之前說過的，我們在第三階段有 15 個 NME，我們將充分發揮這些產品的潛力。因此，對於 camizestrant，dcamera，我想您可以理解我的意思。但這又讓我們不得不繼續在研發方面的投資，我們將把研發支出佔收入的比例保持在 20 多歲，因為我們有很多巨大的機會可以釋放。

On the camizestrant side, I have to say, Susan and the team did a fantastic job taking their time to identify the right approach to dosage, and doing the same now with additional Phase III studies in early treatment. So hopefully, we can make camizestrant a very big product.

在 camizestrant 方面，我不得不說，Susan 和團隊在花時間確定正確的劑量方法方面做得非常出色，現在在早期治療中進行了額外的 III 期研究。因此，希望我們可以使 camizestrant 成為一個非常大的產品。

The next question is Seamus Fernandez.

下一個問題是 Seamus Fernandez。

So just 2 quick ones. First, this is really for Mene. Just trying to understand the opportunity that you see in [BTTR], and the reason for the significant increase in the size of the study? Just want to better understand if you guys are either paying for an earlier interim or a potentially differentiated label? Or if you see potential challenges so that you're just managing for a potentially different effect size just given the competitive landscape? So that's the first question.

所以只有2個快速的。首先，這真的是為了梅內。只是想了解您在 [BTTR] 中看到的機會，以及研究規模顯著增加的原因？只是想更好地了解你們是為早期的臨時標籤還是潛在的差異化標籤付費？或者，如果您看到了潛在的挑戰，那麼您只是在考慮到競爭格局的情況下，才針對可能不同的效應規模進行管理？所以這是第一個問題。

And then the second one, Aradhana, I just wanted to better understand gross margin progression in particular. We're seeing higher margin product actually rolled in quite significantly on the collaboration revenue line. But just trying to get a better understanding of what the offsets are to kind of maintain what is, I believe, has been communicated as a likely roughly 80% gross margin? So just trying to understand why there isn't quite a bit more of an uplift on the gross margin given the collaboration revenue contribution.

然後是第二個，Aradhana，我只是想更好地了解毛利率的進展。我們看到更高利潤的產品實際上在協作收入線上非常顯著。但只是試圖更好地了解抵消是什麼，以維持我認為已經傳達的可能大約 80% 的毛利率？因此，只是想了解為什麼考慮到協作收入的貢獻，毛利率沒有更多的提升。

Mene?

梅內？

Yes. So we increased the study from 1,000 patients to 1,400 patients, and the dosing period from 120 weeks to 140 weeks. And the reason is because we want to absolutely make sure we have a positive study. We're obviously looking at the event rates that we've had and we're also looking at the event rates of our competitors. And so just based on those assumptions, we wanted to make sure that we don't miss the positive mortality benefit by a few cases because we didn't have the right powered study. So it's really to make sure we have a positive study. .

是的。因此，我們將研究從 1,000 名患者增加到 1,400 名患者，給藥期從 120 週增加到 140 週。原因是因為我們要絕對確保我們有一個積極的研究。我們顯然正在查看我們擁有的事件率，我們也在查看我們競爭對手的事件率。因此，僅僅基於這些假設，我們希望確保我們不會因為沒有正確的動力研究而錯過一些病例帶來的積極死亡率益處。所以這真的是為了確保我們有一個積極的研究。 .

Of course, depending on event rates and we never talk interims, but we'll be looking at the data. But the sizing of the study is really to make -- to ensure that we get a positive study.

當然，這取決於事件發生率，我們從不談論臨時性，但我們會查看數據。但是研究的規模確實是為了確保我們得到積極的研究。

Mene. I mean, this -- One of our values is we play to win. And on this one, we really want to play to win and show a mortality benefit, and we potentially could have a product that might be differentiated if we are the product -- if we have the only product that has shown a mortality benefit. And it would be a real shame to miss the mortality endpoint if we could achieve it.

梅內。我的意思是，我們的價值觀之一是我們為勝利而戰。在這一點上，我們真的想贏得比賽並展示死亡率收益，如果我們是產品，我們可能會擁有一種可能與眾不同的產品 - 如果我們擁有唯一顯示死亡率收益的產品。如果我們能夠實現它，錯過死亡率終點將是一個真正的恥辱。

So to address your gross margin question, I think you were referring probably particularly to this year to 2022. And yes, there has been obviously some increase in collaboration revenue. But when you look at the total sort of amount of the collaboration versus our total revenue, that's still a very small percentage of our total revenue. That's one element.

因此，為了解決您的毛利率問題，我認為您可能特別指的是今年到 2022 年。是的，合作收入顯然有所增加。但是，當您查看合作的總金額與我們的總收入相比時，這仍然只占我們總收入的一小部分。這是一個要素。

The second element is relating to COVID medicines. So we did indicate in the middle of the year that we did expect COVID medicines, which included both like (inaudible) and Evusheld to be in line with where we were last year, which was slightly north of [$4 billion]. And (inaudible), as you know, we had a lot of initial contracts and that doesn't really contribute much, and we did mention also that gross margins for Evusheld were expected to be lower than the corporate gross margins.

第二個要素與 COVID 藥物有關。因此，我們確實在年中表示，我們確實預計 COVID 藥物，其中包括（聽不清）和 Evusheld 將與我們去年的情況保持一致，略高於 [40 億美元]。而且（聽不清），如您所知，我們有很多初始合同，但並沒有真正貢獻多少，我們也確實提到 Evusheld 的毛利率預計低於公司毛利率。

And then I would say the third major element is relating to pricing, and particularly pricing in China and some of the emerging markets where pricing is again not as high as it is in the developed markets. So those would probably be elements that contribute to the gross margins.

然後我想說第三個主要因素與定價有關，特別是在中國和一些新興市場的定價，這些市場的定價再次不如發達市場高。因此，這些可能是有助於毛利率的因素。

Sorry,. we were especially asking about go-forward margins, just to clarify. We were not asking about this year's margins.

對不起，。我們特別詢問了前進利潤率，只是為了澄清。我們沒有詢問今年的利潤率。

Yes, I did. I think there was another question relating to long-term margins, which I addressed earlier in the call. But very much sort of the same elements, I would say. Again, would be long-term margins would be -- long-term gross margins would be determined by mix. So the mix of Rare Disease, Oncology as well as the BioPharma products. Again, those all have different margins. The mix of biologics versus small molecules, the mix of emerging markets, China versus some of the developed markets and pricing in those markets, and then the mix of collaboration revenue versus 100% owned revenue. And then the impact of inflation and cost increases that are being passed on to us that we continue to manage through our own efficiency and procurement.

是的，我做到了。我認為還有一個與長期利潤率有關的問題，我在電話會議的早些時候談到了這個問題。但我想說的是非常相似的元素。同樣，長期利潤率將是 - 長期毛利率將由組合決定。因此，罕見病、腫瘤學以及生物製藥產品的組合。同樣，這些都有不同的利潤。生物製劑與小分子的混合，新興市場的混合，中國與一些發達市場的混合以及這些市場的定價，然後是合作收入與 100% 自有收入的混合。然後是通貨膨脹和成本增加的影響，這些影響正在傳遞給我們，我們將繼續通過我們自己的效率和採購來進行管理。

Two specific points. I mean, Lynparza is growing and of course, has a negative effect on margin. The other point that maybe is important to keep in mind is the emerging markets. The emerging markets have they're very accretive in profitability, in profit and dollar profit, but they have -- they tend to have lower gross margin. And then as you could see, as you can see this year, they are growing tremendously. The unmet needs in those countries are enormous and we have a tremendous commercial presence, commercial footprint now. We're rapidly becoming top 3 company in every market around the world. And of course, we're #1 in China in particular, but we're #2, #3 in most of those countries. They're growing very, very rapidly, they; 're generating additional new profit. But the gross margin rate, the percentage is a bit lower. Not massively lower but a bit lower, and it's sort of a drag towards the lower average. So you have puts and takes in this gross margin.

兩個具體點。我的意思是，Lynparza 正在增長，當然，對利潤率有負面影響。可能需要牢記的另一點是新興市場。新興市場的盈利能力、利潤和美元利潤都非常增加，但它們有——它們的毛利率往往較低。然後正如你所看到的，正如你今年所看到的，它們正在大幅增長。這些國家的未滿足需求是巨大的，我們現在擁有巨大的商業存在和商業足跡。我們正在迅速成為全球每個市場的前 3 名公司。當然，我們在中國尤其是第一，但在大多數這些國家中，我們是第二、第三。他們的成長非常非常迅速，他們； '正在產生額外的新利潤。但是毛利率，百分比要低一些。不是大幅降低，而是稍微降低了一點，這有點拖累了較低的平均水平。所以你有這個毛利率的看跌期權。

Peter Welford, Jefferies.

彼得韋爾福德，傑富瑞。

I've got 2.

我有2個。

Firstly, on China. I guess maybe one for Leon, if he's on the call. I'm wondering if in a sort of slowly emerging post-COVID world in China, whether you think we'll see changes in the attitude of those patients and also doctors in terms of treatment? So will we still see patients to the same extent going to hospitals and perhaps going to some of the major cities, or do you think we'll continue to see a more spread out level of care, if you like, in China? And how that impacts your thinking with regards to the commercial footprint in China? Particularly as well, I guess, with regards to something like a Rare Disease unit, where obviously, potentially in the developed world at least, vicinity to patients is often used as a key sort of feature to supply by the drug to the patients in the market?

首先，關於中國。我想可能是給 Leon 的，如果他在電話中的話。我想知道，在中國一個緩慢興起的後疫情時代，您是否認為我們會看到這些患者以及醫生在治療方面的態度發生變化？那麼我們是否還會看到同樣程度的患者去醫院，或者去一些大城市，或者你認為我們會繼續在中國看到更分散的護理水平嗎？這如何影響您對中國商業足蹟的看法？特別是，我猜想，對於像罕見病單位這樣的東西，顯然，至少在發達國家，靠近患者經常被用作藥物向患者提供藥物的關鍵特徵。市場？

And then secondly, a slightly, I guess, [annual] question perhaps for Aradhana. But I wonder if you could just talk us through what seems to have happened to the sort of FX, or how we should think about the FX impact on your cost base? I guess since taking over Alexion, the level of natural hedge, if we call it that, in the margin that Astra used to have seems to have somewhat declined and there's more impact now on the profit from the dollar move we're seeing. Can you just talk a little bit about -- I guess, how we should think about Alexion, I'm assuming that is what it is impact on the cost base, has driven that change?

其次，我想，可能是對阿拉達納的一個輕微的[年度]問題。但是我想知道您是否可以告訴我們這種外匯似乎發生了什麼，或者我們應該如何考慮外匯對您的成本基礎的影響？我想自從接管 Alexion 以來，自然對沖水平，如果我們這麼稱呼的話，Astra 過去的利潤率似乎有所下降，現在對我們看到的美元走勢的利潤產生了更大的影響。你能談談 - 我想，我們應該如何看待 Alexion，我假設這就是它對成本基礎的影響，推動了這種變化？

Okay. So Leon, do you want to take the first question?

好的。所以Leon，你想回答第一個問題嗎？

Yes. Yes. I think COVID business is still happening in China. And also, China is still taking 0 COVID policy. So patients for short treatment, acute treatment like (inaudible) nebulized, these are part of some more impacted versus oncology and chronic disease management type products. .

是的。是的。我認為 COVID 業務仍在中國發生。而且，中國仍在採取零疫情政策。因此，對於短期治療、急性治療（如（聽不清）霧化的患者），這些是與腫瘤學和慢性病管理類型產品相比受影響更大的一部分。 .

So I think -- and the common impact now is still additive to the hospital patient visit in 30% of the urban population. But AstraZeneca is a widespread covering company and the #1 company in China, so we are covering multiple channels and the community center, county hospital, online. So today is [Double 11], so I think there's a lot of -- even prescription medicine are refilled online with prescriptions for chronic disease refill prescription.

所以我認為 - 現在的共同影響仍然是 30% 城市人口的醫院病人就診。但阿斯利康是一家覆蓋面廣的公司，也是中國排名第一的公司，所以我們覆蓋了多個渠道和社區中心、縣醫院、在線。所以今天是[雙11]，所以我認為有很多——甚至是處方藥都在網上補充了慢性病補充處方的處方。

So I think as we look at (inaudible) manage this clear situation better than other [content], but [differed] by products.

所以我認為，當我們看到（聽不清）比其他 [內容] 更好地管理這個明確的情況時，但 [不同] 產品。

For Rare Disease, I think is still underdiagnosed and also affordability a primary issue in China. So if affordability can be the situation can be improved with (inaudible) and commercial insurance and the charity program and also company support, patient support program, so then we can definitely improve the treatment and diagnosis rate in China for Rare Disease.

對於罕見病，我認為仍然未被充分診斷，負擔能力也是中國的主要問題。因此，如果可以通過（聽不清）商業保險和慈善計劃以及公司支持、患者支持計劃來改善這種情況，那麼我們絕對可以提高中國罕見病的治療和診斷率。

Leon. Aradhana?

萊昂。阿拉達納？

So again, we did give some sensitivity analysis relating to what the FX impact is. I think your question was also relating to what the FX impact is on the Alexion business.

因此，我們再次對外匯影響進行了一些敏感性分析。我認為您的問題也與外匯對 Alexion 業務的影響有關。

So in our AstraZeneca business, most of our manufacturing costs are actually in pounds and Swedish krona, that's where most of our manufacturing is located. For the Alexion business as well, actually, most of their manufacturing is located in Ireland, so it's euro-denominated. As well as sourced from other CMOs, which are also outside the U.S. So I think that's -- those are the currency impacts that you would have on the COGS line.

因此，在我們的阿斯利康業務中，我們的大部分製造成本實際上以英鎊和瑞典克朗為單位，這是我們大部分製造所在的地方。實際上，對於 Alexion 業務而言，他們的大部分製造都位於愛爾蘭，因此以歐元計價。以及來自其他也在美國以外的 CMO。所以我認為這就是你對 COGS 線的貨幣影響。

Adam Karlsson, ABG.

亞當卡爾森，ABG。

A couple on Beyfortus. We've now got data for (inaudible) in the maternal setting, so I wanted to get your thoughts on how you feel, something about [compares] thinking in particular on the relevance of the efficacy drop-off with RSV [PF] between 3 and 6 months?

Beyfortus 上的一對夫婦。我們現在已經獲得了孕產婦環境中（聽不清）的數據，所以我想了解您對您的感受的看法，關於 [比較] 尤其是關於功效下降與 RSV [PF] 之間的相關性的思考3個月和6個月？

Secondly, Pfizer have talked of the value of the vaccine providing protection right from birth, although I guess this potential advantage would have been reflected in the data set so far. Your thoughts on this, and specifically, what is your expectation around when and where post-birth and the (inaudible) will be administered? Could it be already in the hospital or center for discharge?

其次，輝瑞公司談到了疫苗從出生就提供保護的價值，儘管我猜這種潛在的優勢已經反映在迄今為止的數據集中。您對此有何看法，具體來說，您對分娩後何時何地實施以及（聽不清）實施的期望是什麼？它可能已經在醫院或中心出院了嗎？

And just finally, if I could squeeze in a final one on (inaudible), zooming out a little bit. Any updates on the anticipated time line for bringing (inaudible) into the adult setting? And with the credit picture in RSV now crystallizing, has that influenced how you think about, or let's say, your interest in behalf of the U.S. (inaudible) profits you previously held rights to?

最後，如果我可以在（聽不清）上擠上最後一個，縮小一點。將（聽不清）帶入成人環境的預期時間表是否有任何更新？隨著 RSV 中的信用圖片現在逐漸清晰，這是否影響了您如何看待，或者說，您代表您之前持有的美國（聽不清）利潤的利益？

Adam. So I'll ask Iskra to cover those questions.

亞當。所以我會請《火星報》回答這些問題。

On the adult form, really our priority is pediatrics for now, and I don't think we would want to talk about the adult formulation. The key priority for this product is really the pediatric form.

在成人形式上，我們現在的首要任務是兒科，我認為我們不想談論成人形式。該產品的關鍵優先級實際上是兒科形式。

Yes, absolutely. We are very pleased with the recent approvals of the -- in Europe and in U.K., and we are very much focusing on bringing [nirsevimab] to the infants and working with regulators -- with the other regulators and also with the payers to make sure that we bring it across the globe.

是的，一點沒錯。我們對最近在歐洲和英國獲得的批准感到非常滿意，我們非常專注於將 [nirsevimab] 帶給嬰兒並與監管機構合作——與其他監管機構以及付款人合作，以確保我們把它帶到全球。

I think it's good to remind everybody on the exciting data we recently presented, and then put that in the context of the maternal vaccine as per your question. So if you remember, we presented our data and pooled analysis of MELODY/MEDLEY showing 79.5% efficacy against all low respiratory tract infection in the infants, and very importantly, during the -- through our -- the whole season. And if you look at the high-level data of the maternal vaccine, it seems that the efficacy against low respiratory tract infection is decreasing over the time, and it is increasing around month #3 or month #4.

我認為最好提醒大家我們最近提供的令人興奮的數據，然後根據您的問題將其放在孕產婦疫苗的背景下。因此，如果您還記得，我們提供了我們的數據和 MELODY/MEDLEY 的匯總分析，顯示對嬰兒所有低呼吸道感染的療效為 79.5%，非常重要的是，在整個賽季期間。而且，如果您查看母體疫苗的高水平數據，似乎對抗低呼吸道感染的功效隨著時間的推移而下降，並且在第 3 個月或第 4 個月左右呈上升趨勢。

Now if you think about the way how antibody applied versus maternal vaccination, before, this will basically be given to the infants either at the time of birth if in the season or later on in the beginning of the season. And based on our data in both cases, infants will be fully protected throughout the whole season. And the maternal vaccination, it depends when the mothers are vaccinated. And that definitely means that with diminishing efficacy after 3 or 4 months, many of the infants may not have the full protection throughout the season, which I believe makes a significant difference between the antibody and the maternal vaccination.

現在，如果您考慮一下抗體應用與母體疫苗接種的方式，以前，這基本上將在嬰兒出生時（如果在季節）或稍後在季節開始時給予嬰兒。根據我們在這兩種情況下的數據，嬰兒將在整個季節得到充分保護。而產婦接種疫苗，則取決於母親何時接種疫苗。這絕對意味著，隨著 3 或 4 個月後功效的減弱，許多嬰兒可能在整個季節都沒有得到充分的保護，我相信這在抗體和母體疫苗接種之間產生了顯著差異。

Part of your question is around the -- whether the (inaudible) will be initiated. I mean, on my side, I think you understand that that obviously depends on how different health care systems are set across the geography. Particularly, as mentioned, it can be administrated either at birth in the hospital if it's within the season, or later on at any point, either hospital or at the primary care.

您的部分問題是關於- 是否會啟動（聽不清）。我的意思是，就我而言，我認為你理解這顯然取決於不同地區的醫療保健系統是如何設置的。特別是，如前所述，它可以在出生時在醫院進行管理，如果它在季節內，或者稍後在任何時候，無論是醫院還是初級保健。

Iskra. Important point to remember because if a mother is vaccinated out of season and the baby is born out of season, then basically when the season comes, there's no protection left with the vaccine. I mean, so it works both ways. And this product, [nacelumab] is really, in the end, the best protection for babies.

火星報。重要的一點要記住，因為如果母親在反季節接種疫苗而嬰兒在反季節出生，那麼基本上當季節到來時，疫苗就沒有保護作用了。我的意思是，所以它是雙向的。而這個產品，[nacelumab]，說到底，真的是對嬰兒最好的保護。

Luisa Hector of Berenberg.

貝倫貝格的路易莎·赫克托。

Pascal.

帕斯卡。

Maybe to follow up on R&D. I just wonder what the impact of inflation is on the cost of running the big Phase III trials and whether you have incorporated IRA into your R& D investment decision process already?

也許是為了跟進研發。我只是想知道通貨膨脹對運行大型 III 期試驗的成本有什麼影響，以及您是否已經將 IRA 納入您的研發投資決策過程？

Aradhana, do you want to take the first one and maybe Mene and Susan could give comments on the second question?

Aradhana，你要不要回答第一個問題，也許 Mene 和 Susan 可以對第二個問題發表評論？

We are seeing some impact of inflation on the cost of our clinical studies. Not just the impact of inflation, but also the impact of some of the labor shortages, which includes nurses and doctors and facility shortages that a lot of the sites are experiencing. So we are seeing some impact of that on our studies.

我們看到通貨膨脹對我們臨床研究成本的一些影響。不僅是通貨膨脹的影響，還有一些勞動力短缺的影響，其中包括護士和醫生以及許多工廠正在經歷的設施短缺。所以我們看到這對我們的研究產生了一些影響。

And then maybe Dave can address the question on the inflation reduction.

然後也許戴夫可以解決通貨膨脹降低的問題。

So from an R&D perspective, was how much is it impacting R&D? So I would say as we do every year, we look at the business cases, launch dates of all of our indications, the (inaudible) or LCMs, and we make our prioritization based on that. And of course, the Inflation Reduction Act is part of that assessment now. .

那麼從研發的角度來看，它對研發的影響有多大？因此，我想說，就像我們每年所做的那樣，我們會查看業務案例、所有適應症的發布日期、（聽不清）或 LCM，並以此為基礎確定優先級。當然，《降低通貨膨脹法》現在是該評估的一部分。 .

What I would say is the piece that concerns me the most is the big difference between small molecules and large molecules, the 9 versus 13 years. Because I think, obviously, that adds some complexity to actually the mix of your pipeline. And so I would say it has the potential to encourage us to disinvest in small molecules potentially relative to larger molecules or more complex modalities because they'll have a longer exclusivity period.

我想說的是，我最關心的是小分子和大分子之間的巨大差異，即 9 年與 13 年。因為我認為，顯然，這增加了實際管道組合的一些複雜性。所以我想說，它有可能鼓勵我們減少對可能相對於大分子或更複雜模式的小分子的投資，因為它們將有更長的排他期。

There are 2 major problems with this one is the small molecule point that many was raising. And the second is there is incentive to start with small indications that's mostly true for oncology, where if you have to start with the third line indications, patients would benefit from this. But we may not do it in the future or not launch in the U.S., We may launch elsewhere in the world, but not launch in the U.S. until we have approval for a larger indication, because the clock starts as soon as you get approval. So that's -- those are really negative factors that are real problems with investment -- this inflation reducing a low.

這有兩個主要問題是許多人提出的小分子點。第二個是有動力從小適應症開始，這對腫瘤學來說主要是正確的，如果你必須從三線適應症開始，患者會從中受益。但是我們將來可能不會這樣做，或者不會在美國推出，我們可能會在世界其他地方推出，但在我們批准更大的適應症之前不會在美國推出，因為一旦你獲得批准，時鐘就開始了。所以這就是——這些都是真正的負面因素，是投資的真正問題——通脹降低了一個低點。

So with this, I would like to thank you all for your interest in our company, and wish you all a good rest of the day. Thank you.

因此，我要感謝大家對我們公司的關注，並祝大家今天休息愉快。謝謝你。