莫德納 (MRNA) 2021 Q3 法說會逐字稿

Good morning, and welcome to Moderna's Third Quarter Earnings Call. (Operator Instructions)

早上好，歡迎來到 Moderna 的第三季度財報電話會議。 （操作員說明）

Please be advised that the call is being recorded. At this time, I'd like to turn the call over to Lavina Talukdar, Head of Investor Relations at Moderna. Please go ahead, ma'am.

請注意，通話正在錄音中。此時，我想將電話轉給 Moderna 投資者關係主管 Lavina Talukdar。請繼續，女士。

Thank you, operator. Good morning, everyone, and thank you for joining us on today's call to discuss Moderna's third quarter 2021 financial results and business updates. You can access the press release we issued this morning as well as the slides that we'll be reviewing by going to the Investors section of our website.

謝謝你，接線員。大家早上好，感謝您加入我們今天的電話會議，討論 Moderna 2021 年第三季度的財務業績和業務更新。您可以訪問我們網站的“投資者”部分，訪問我們今天上午發布的新聞稿以及我們將審查的幻燈片。

On today's call are Stephane Bancel, our Chief Executive Officer; David Meline, our Chief Financial Officer; Stephen Hoge, our President; and Paul Burton, our Chief Medical Officer.

今天的電話是我們的首席執行官 Stephane Bancel；我們的首席財務官 David Meline；我們的總裁斯蒂芬·霍格；和我們的首席醫療官 Paul Burton。

Before we begin, please note that this conference call will include forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Please see Slide 2 of the accompanying presentation and our SEC filings for important risk factors that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements.

在我們開始之前，請注意，本次電話會議將包括根據 1995 年《私人證券訴訟改革法案》的安全港條款做出的前瞻性陳述。請參閱隨附演示文稿的幻燈片 2 和我們提交給 SEC 的重要風險因素可能導致我們的實際業績和結果與這些前瞻性陳述中明示或暗示的內容存在重大差異。

On Slide 3, please see the important indication and safety information from our COVID-19 vaccine, which has been arrived for emergency use in the United States and many other countries around the world.

在幻燈片 3 上，請查看我們的 COVID-19 疫苗的重要適應症和安全信息，該疫苗已在美國和世界上許多其他國家緊急使用。

I will now turn the call over to Stephane.

我現在將把電話轉給 Stephane。

Thank you, Lavina. Good morning or good afternoon, everyone. Welcome to our Q3 2021 conference call. Today, I will start by a quick business review of the quarter before David presents the key financials. Paul will then walk you through some real-world evidence update, and Stephen will provide a clinical development update. I will then come back to close to share some thoughts about where we are heading.

謝謝你，拉維娜。大家早上好或下午好。歡迎來到我們的 2021 年第三季度電話會議。今天，在大衛介紹關鍵財務數據之前，我將首先對本季度的業務進行快速回顧。然後，保羅將引導您完成一些真實世界的證據更新，斯蒂芬將提供臨床開發更新。然後我會回來分享一些關於我們前進方向的想法。

Let's start on Slide 5 with a holistic pipeline update. First, respiratory vaccines.

讓我們從幻燈片 5 開始，全面更新管道。首先，呼吸道疫苗。

We are pleased to have filed the BLA for COVID-19 vaccine to FDA and have now received a priority review designation. We received our first full approval for Spikevax back in Canada. We received EUA from the FDA for a 50-microgram booster and mix and match has been authorized. We also received authorization for boosters from other major geographies, EMEA, U.K. and so on. We were informed recently that the FDA may take until January 2022 to review the EUA request for 12 to 17 years of age.

我們很高興向 FDA 提交了 COVID-19疫苗的 BLA，現在已獲得優先審查指定。我們在加拿大首次獲得了 Spikevax 的完全批准。我們從 FDA 收到了 50 微克助推器的 EUA，並且混合和匹配已獲得授權。我們還獲得了來自其他主要地區、歐洲、中東和非洲、英國等地的助推器授權。我們最近獲悉，FDA 可能需要到 2022 年 1 月才能審查 12 至 17 歲的 EUA 請求。

Turning now to flu, mRNA-1010 is fully enrolled for the Phase I and we expect human data soon now. For RSV, mRNA-1345, after very positive data in the Phase I with high neutralizing antibody levels after 1 dose, our teams are finalizing the preparation of the Phase II/III in all the adults. This study should start soon.

現在轉向流感，mRNA-1010 已完全進入第一階段，我們預計很快就會有人類數據。對於 RSV，mRNA-1345，在第一階段的非常積極的數據和 1 劑後的高中和抗體水平之後，我們的團隊正在完成所有成人的第二階段/第三階段的準備工作。這項研究應該很快開始。

We also announced our development candidate for COVID booster plus flu booster in a single dose, mRNA-1073, which we anticipate will be in the clinic soon.

我們還宣布了我們的單劑量 COVID 增強劑和流感增強劑的開發候選藥物 mRNA-1073，我們預計它將很快進入臨床。

Let me now turn to vaccine against latent viruses. As many of you know, latent viruses are a major cause of health problems. Latent viruses are made of DNA viruses. And once a human is infected by latent virus, that virus will stay in the body. You are familiar with some latent viruses like HIV and HPV. There are many others that harms humans.

現在讓我談談針對潛伏病毒的疫苗。眾所周知，潛伏病毒是導致健康問題的主要原因。潛伏病毒由DNA病毒組成。一旦一個人被潛伏病毒感染，該病毒就會留在體內。您熟悉一些潛伏病毒，例如 HIV 和 HPV。還有許多其他危害人類的東西。

As a company, we are committed to developing a portfolio of first-in-class vaccines and therapeutics against these latent viruses.

作為一家公司，我們致力於開發針對這些潛伏病毒的一流疫苗和療法組合。

Our first programs are CMV vaccine, EBV vaccine and EBV therapeutic vaccine. We have also partnered to work on 2 HIV vaccines.

我們的第一個項目是 CMV 疫苗、EBV 疫苗和 EBV 治療性疫苗。我們還合作開發了 2 種 HIV 疫苗。

Last week marked a big milestone for Moderna. We started hosting in the clinic the first participants of our Phase III pivotal registration study for CMV vaccine mRNA-1647. This marks the second Phase III study that the company has started and brings us one step closer to getting another important vaccine to millions of people around the world.

上周是 Moderna 的一個重要里程碑。我們開始在診所接待 CMV 疫苗 mRNA-1647 III 期關鍵註冊研究的第一批參與者。這標誌著該公司已經啟動的第二項 III 期研究，使我們離為全球數百萬人提供另一種重要疫苗又近了一步。

Our EBV vaccine, mRNA-1189 should start dosing for its Phase I very soon. And our new development candidate on the EBV therapeutic vaccine, mRNA-1195, is moving toward the clinic.

我們的 EBV 疫苗 mRNA-1189 應該很快開始為其 I 期給藥。我們在 EBV 治療疫苗上的新開發候選藥物 mRNA-1195 正在走向臨床。

Let me now turn to therapeutics. Our personalized cancer vaccine is in Phase II. KEYTRUDA monotherapy is fully enrolled, and we expect data in the back end of 2022. Our genetic programs continued to progress well in the clinic. PA has its Phase I dose cohort fully enrolled. MMA is dosing patients in its Phase I. GSD1a has an open IND and has received Orphan Drug Designation by FDA.

現在讓我談談治療學。我們的個性化癌症疫苗處於 II 期。 KEYTRUDA 單藥療法已全部入組，我們預計 2022 年年底會有數據。我們的基因項目在臨床上繼續取得良好進展。 PA 的 I 期劑量隊列已完全註冊。 MMA 正在對 I 期患者進行給藥。GSD1a 具有開放的 IND 並已獲得 FDA 的孤兒藥指定。

So as you can see, we have got 3 rare genetic disease programs in the clinic or soon to be in the clinic. So we look forward to sharing clinical data in the coming months.

如您所見，我們有 3 個罕見遺傳疾病項目正在臨床或即將進入臨床。因此，我們期待在未來幾個月內分享臨床數據。

We are very proud to have found the way to get Crigler Najjar type 1 of CN-1 to patients through a donation of IP and the assets to the institute for life-changing medicines. CN-1 disease is a ultra-rare disease with very few patients afflicted around the world. For ultra-rare disease, just because of clinical development will result in a very high price for a few patients around the world that could benefit.

我們很自豪能夠通過將知識產權和資產捐贈給改變生命的藥物研究所，將 CN-1 的 Crigler Najjar 1 型提供給患者。 CN-1 病是一種極其罕見的疾病，全世界很少有患者患病。對於超罕見病，僅僅因為臨床開發，就會導致全球少數可能受益的患者付出非常高的代價。

This model is not one that we support. So instead of developing the drug and charging a very high price, we decided to give the drug away and innovate through a creative partnership. We provide the drug to the institutes. We pay for clinical trial material, the institute pays for the clinical trial cost. If a drug is approved, we'll provide the medicines to the kids and their families for free. And we will not charge any royalty or milestone to the institutes. We believe this is the right thing to do to continue to contribute to society for ultra-rare disease where our mRNA platform can help.

我們不支持這種模式。因此，我們沒有開發這種藥物並收取很高的價格，而是決定將這種藥物贈送出去，並通過創造性的合作夥伴關係進行創新。我們向研究所提供藥物。我們支付臨床試驗材料，研究所支付臨床試驗費用。如果藥物獲得批准，我們將免費為孩子及其家人提供藥物。我們不會向這些機構收取任何版稅或里程碑費用。我們相信，在我們的 mRNA 平台可以提供幫助的情況下，繼續為超罕見疾病社會做出貢獻是正確的做法。

One of the important news item announced today is the introduction of a new modality to our existing 6 modalities. We are very pleased to announce that Vertex and Moderna are now in GLP tox studies for the cystic fibrosis program, VXc-522.

今天宣布的重要新聞之一是在我們現有的 6 種模式中引入一種新模式。我們很高興地宣布，Vertex 和 Moderna 現在正在為囊性纖維化計劃 VXc-522 進行 GLP 毒性研究。

This marks our first inhaled pulmonary therapeutics program. I would like to congratulate and thank our scientific team as well as the Vertex team for having been able to develop a novel lipid formulation to allow inhaled pulmonary delivery. This is really exciting for patients.

這標誌著我們的第一個吸入肺治療計劃。我要祝賀並感謝我們的科學團隊以及 Vertex 團隊能夠開發出一種新的脂質製劑以允許吸入肺輸送。這對患者來說真的很令人興奮。

As we communicated previously, in addition to doing therapeutics using mRNA coding for human proteins like the ones I just described, we want to use our mRNA plus lipid technologies to develop therapeutics using mRNA coding for gene editing enzymes. We are pleased to announce our first partnership in that field. We announced earlier this week that we entered into a licensing collaboration with Metagenomi based in California, to use their next-generation gene editing enzymes. We believe that their technology coupled with our mRNA plus lipid technologies, and our manufacturing infrastructure will produce some exciting new medicine to take into the clinic. I am very pleased with the progress of the company. We are increasing depth in vaccines and at the same time, increasing breadth of application with our 7 modalities the lung and gene editing.

正如我們之前所交流的，除了像我剛才描述的那樣使用編碼人類蛋白質的 mRNA 進行治療外，我們還希望使用我們的 mRNA 加脂質技術來開發使用 mRNA 編碼基因編輯酶的治療方法。我們很高興地宣布我們在該領域的第一個合作夥伴關係。我們本週早些時候宣布，我們與位於加利福尼亞的 Metagenomi 進行了許可合作，以使用他們的下一代基因編輯酶。我們相信，他們的技術與我們的 mRNA 加脂質技術以及我們的製造基礎設施相結合，將生產出一些令人興奮的新藥進入臨床。我對公司的進步感到非常高興。我們正在增加疫苗的深度，同時通過我們的 7 種肺和基因編輯方式增加應用的廣度。

On Slide 6, you will find financial highlights. For Q3, we reported revenue of around $5 billion, enabled by delivering 208 million doses of our COVID-19 vaccine. Net income of $3.3 billion. Our cash and cash equivalents position was $15 billion at the end of September.

在幻燈片 6 上，您會看到財務亮點。第三季度，我們報告的收入約為 50 億美元，這得益於我們提供了 2.08 億劑 COVID-19 疫苗。淨收入33億美元。截至 9 月底，我們的現金和現金等價物頭寸為 150 億美元。

Since the end of the quarter, we have been working to gain better visibility into those variables that will impact our full year results. And we have much better visibility today than we did a month ago.

自本季度末以來，我們一直在努力更好地了解那些將影響我們全年業績的變量。我們今天的能見度比一個月前要好得多。

For fiscal year 2021, we are updating the range of doses we plan to deliver to 700 million to 800 million doses. The key variable of this update volume range are: first, longer lead time for exports to countries outside the U.S. and for international shipments in general.

在 2021 財年，我們正在將計劃提供的劑量範圍更新為 7 億至 8 億劑。此更新量範圍的關鍵變量是：首先，出口到美國以外的國家和一般國際貨運的交貨時間更長。

In Q3, we shipped more deliveries to new international market and expect Q4 to also have more international deliveries. As we deliver to these countries for the first time, we expect the process to become more a routine and delivery time to short term. However, some Q4 deliveries may still move to early 2022 as a result.

在第三季度，我們向新的國際市場運送了更多的貨物，並預計第四季度也將有更多的國際交付。當我們第一次向這些國家/地區交付時，我們預計該過程將變得更加常規和短期交付時間。然而，一些第四季度的交付可能仍會因此推遲到 2022 年初。

Second, in Q3, we have expanded our fill finish capacity with our manufacturing partners, which has the temporary impact on our shipments. That work is complete now, and we should see a positive impact from this expansion very soon.

其次，在第三季度，我們與製造合作夥伴擴大了填充完成能力，這對我們的出貨量產生了暫時的影響。這項工作現在已經完成，我們應該很快就會看到這種擴張帶來的積極影響。

Third, the bottleneck of production has moved down the manufacturing line to product release. We added additional resources, skilled personnel to the release and of the manufacturing line, and we expect to increase the weekly number of doses released.

三是生產瓶頸下移至產品發布。我們為釋放和生產線增加了額外的資源和技術人員，我們預計每週釋放的劑量數量會增加。

We believe resolution of these factors put us in a good position heading into Q4 and 2022.

我們相信，這些因素的解決使我們在進入第四季度和 2022 年時處於有利位置。

Now if I turn to revenue for '21. The updated revenue range for 2021 is $15 billion to $18 billion. This range reflects updated delivery schedule with fewer doses delivered in '21, as some doses are pushed into 2022. And also, the pricing impact of prioritization delivery to COVAX and African Union that have a lower tier pricing.

現在，如果我轉向 21 年的收入。 2021 年更新後的收入範圍為 150 億美元至 180 億美元。該範圍反映了更新的交付時間表，21 年交付的劑量減少，因為一些劑量被推到 2022 年。此外，優先交付給 COVAX 和非洲聯盟的定價影響較低，它們的定價較低。

On Slide 7, let me start by summarizing the scale of operational challenges that the team had to work through, as we scale for making less than 100,000 doses in [2020] to hundreds of millions of doses in 2021. Q1 scale-up challenges were around drug substance, making mRNA in lipid.

在幻燈片 7 上，讓我首先總結一下團隊必須克服的運營挑戰的規模，因為我們將在 [2020] 年生產不到 100,000 劑疫苗，到 2021 年生產數億劑疫苗。第一季度擴大規模的挑戰是圍繞藥物物質，在脂質中製造mRNA。

To do scale-up challenges, we're on drug product and ensuring we could fill in our pipes. In the first half of the year, we made great progress in these challenges, as you can see from the numbers on the right. We now have 901 million doses of drug substance that have been formulated and a large volume bags of mRNA product. And we have 770 million doses of drug products already in vials. To do scale-up challenges, we're on product release as the supply chain became more complex with increased deliveries to many countries around the world.

為了應對擴大規模的挑戰，我們正在研究藥品並確保我們可以填補我們的管道。上半年，我們在這些挑戰上取得了很大進展，如右圖所示。我們現在有 9.01 億劑已配製的原料藥和大量袋裝的 mRNA 產品。我們已經有 7.7 億劑藥品裝在小瓶中。為了應對擴大規模的挑戰，我們正在發布產品，因為供應鏈變得更加複雜，向全球許多國家的交付增加。

At the beginning of the year, we supplied just a few large countries.

今年年初，我們只供應了幾個大國。

As mentioned before, we are working through this challenges, and as November [1], we achieved 566 million doses around the world. With the progress year-to-date, we expect to be able to deliver to 700 million to 800 million doses for the full year 2021.

如前所述，我們正在應對這些挑戰，截至 11 月 [1]，我們在全球實現了 5.66 億劑疫苗。隨著年初至今的進展，我們預計能夠在 2021 年全年提供 7 億至 8 億劑疫苗。

We were pleased to be named last week for the seventh year in a row as 1 of the top 20 biotech and pharmacal company in the world by science. We continue to invest in science and the culture of our team. We aim at building the best mRNA science in the world in the culture of boldness, collaboration, curiosity and relentlessness.

我們很高興上周連續第七年被科學評為全球 20 強生物技術和製藥公司之一。我們繼續投資於科學和我們團隊的文化。我們的目標是在大膽、合作、好奇和無情的文化中建立世界上最好的 mRNA 科學。

On Slide 9, you will find our usual summary slide, which describes some of the key high-level attributes of the company as of today.

在幻燈片 9 上，您會看到我們常用的摘要幻燈片，它描述了公司截至目前的一些關鍵高級屬性。

Now let me turn it over to David.

現在讓我把它交給大衛。

Okay. Thank you, Stephane. We're providing today the analysis of actual 2021 third quarter results, along with an updated view of key drivers of financial performance going forward. Turning now to Slide 11 starting with an overview of our sales performance before commenting more broadly on our financial results.

好的。謝謝你，斯蒂芬。我們今天提供對 2021 年第三季度實際業績的分析，以及對未來財務業績關鍵驅動因素的更新視圖。現在轉到幻燈片 11，首先概述我們的銷售業績，然後再更廣泛地評論我們的財務業績。

Total product sales in the third quarter were $4.8 billion, representing 208 million doses delivered to our customers. This compares to sales of $4.2 billion and 199 million doses in Q2 and sales of $1.7 billion and 102 million doses in Q1 of this year.

第三季度的產品總銷售額為 48 億美元，相當於向我們的客戶交付了 2.08 億劑。相比之下，今年第二季度的銷售額為 42 億美元和 1.99 億劑，今年第一季度的銷售額為 17 億美元和 1.02 億劑。

Sales to the U.S. government were $1.2 billion in the third quarter reflecting 73 million doses delivered compared to $2.1 million and 126 million doses in Q2 and sales of $1.4 billion and 88 million doses in Q1.

第三季度對美國政府的銷售額為 12 億美元，反映出交付的劑量為 7300 萬劑，而第二季度為 210 萬美元和 1.26 億劑，第一季度的銷售額為 14 億美元和 8800 萬劑。

Sales to the rest of the world were $3.6 billion in the third quarter, reflecting 136 million doses delivered compared to sales of $2.1 billion and 73 million doses in Q2 and $0.4 billion of sales and 14 million doses in Q1.

第三季度對世界其他地區的銷售額為 36 億美元，其中交付了 1.36 億劑，而第二季度的銷售額為 21 億美元和 7300 萬劑，第一季度的銷售額為 4 億美元和 1400 萬劑。

This reflects the significant manufacturing ramp up outside the U.S. over the last 2 quarters. The relatively modest increase of delivered doses in Q3 versus Q2 was driven by the factors that Stephane just explained. We continue to scale our production network and are working to achieve an increased quarter-over-quarter improvement starting in Q4.

這反映了過去兩個季度美國以外地區製造業的顯著增長。第 3 季度與第 2 季度相比，遞送劑量的相對適度增加是由 Stephane 剛剛解釋的因素驅動的。我們將繼續擴展我們的生產網絡，並努力從第四季度開始實現季度環比增長。

Turning to Slide 12. The transformation of Moderna from an R&D-focused biotech to a commercial company continues to be very apparent when reviewing our financial results. The comparison of the third quarter of 2021 to prior year is not meaningful due to our significant growth, which is why we will primarily focus on the quarter-over-quarter comparison relative to Q2 on the slide.

轉到幻燈片 12。在審查我們的財務業績時，Moderna 從以研發為重點的生物技術公司向商業公司的轉變仍然非常明顯。由於我們的顯著增長，2021 年第三季度與上一年的比較沒有意義，這就是為什麼我們將主要關注幻燈片上相對於第二季度的季度環比比較。

Total revenue was $5 billion in the third quarter of 2021 and compared to $4.4 billion in the second quarter and $0.2 billion in the prior year period. The increase of total revenue is driven by the sale of the company's COVID-19 vaccine. Product sales in Q3 were $4.8 billion compared to $4.2 billion in the second quarter, an increase of 15%. Cost of sales was $722 million or 15% of the company's product sales in the third quarter compared to $750 million or 18% of product sales in the second quarter.

2021 年第三季度的總收入為 50 億美元，而第二季度為 44 億美元，去年同期為 2 億美元。總收入的增長是由公司 COVID-19疫苗的銷售推動的。第三季度的產品銷售額為 48 億美元，比第二季度的 42 億美元增長 15%。第三季度銷售成本為 7.22 億美元，占公司產品銷售額的 15%，而第二季度為 7.5 億美元，佔產品銷售額的 18%。

The quarter-over-quarter percentage improvement is driven by higher average selling price as a result of shifts in our customer mix and to a smaller extent by favorable manufacturing costs.

季度環比百分比的提高是由於我們的客戶組合發生變化導致平均銷售價格上漲，以及在較小程度上是由於有利的製造成本。

Research and development expenses were $521 million in the third quarter, up from $421 million in Q2 and $344 million in the same period in 2020. The higher spend versus prior quarter and prior year was driven by increased COVID-19 vaccine clinical development activities, including our announced efforts around booster variant-specific and multivalent vaccine candidates. Headcount increases as well as external costs to support our growing and maturing development pipeline beyond the COVID-19 vaccine activities also contributed to the expense increase.

第三季度的研發費用為 5.21 億美元，高於第二季度的 4.21 億美元和 2020 年同期的 3.44 億美元。與上一季度和上年相比支出增加的原因是 COVID-19 疫苗臨床開發活動增加，包括我們宣布圍繞加強變體特異性和多價候選疫苗開展工作。除了 COVID-19 疫苗活動之外，為支持我們不斷增長和成熟的開發渠道而增加的員工人數以及外部成本也導致了費用的增加。

Selling, general and administrative expenses were $168 million for Q3 compared to $121 million in the prior quarter and $48 million for the same period in the prior year.

第三季度的銷售、一般和管理費用為 1.68 億美元，上一季度為 1.21 億美元，上年同期為 4800 萬美元。

The growth in spending was driven by the commercialization of our COVID-19 vaccine globally with continued investments in personnel and outside services in support of the accelerated company build-out.

支出的增長是由我們的 COVID-19 疫苗在全球的商業化推動的，並持續投資於人員和外部服務，以支持公司加速擴張。

Provision for income taxes was $219 million in the third quarter, following $283 million in Q2 and an insignificant amount in the prior year. Our effective tax rate for the third quarter was 6%.

第三季度的所得稅準備金為 2.19 億美元，第二季度為 2.83 億美元，而上一年的數額微不足道。我們第三季度的有效稅率為 6%。

Let me remind you of the fact that we had a net operating loss carryforward of $2.3 billion at the end of 2020. This year, we started to release the valuation allowance against the related deferred tax assets, which results in an estimated nonrecurring full year benefit to our effective tax rates of about 5 percentage points.

讓我提醒您一個事實，我們在 2020 年底結轉了 23 億美元的淨營業虧損。今年，我們開始針對相關的遞延所得稅資產釋放估值準備金，這導致估計的非經常性全年收益我們的有效稅率約為 5 個百分點。

Our Q3 effective tax rate was lower than the U.S. statutory rate, primarily due to the just described benefit related to the release of the valuation allowance, the foreign-derived intangible income deduction and an excess tax deduction related to stock-based compensation. This last item drove the quarter-over-quarter reduction due to the increase in our share price in Q3 versus Q2.

我們的第三季度有效稅率低於美國法定稅率，主要是由於剛剛描述的與釋放估值津貼、外國無形收入扣除和與股票補償相關的超額稅收扣除相關的好處。由於我們在第三季度與第二季度的股價上漲，最後一項推動了季度環比下降。

We recorded net income of $3.3 billion in Q3 compared to $2.8 billion in Q2, an increase of 20%. This compares to a loss of $0.2 billion in Q3 of last year.

我們在第三季度錄得 33 億美元的淨收入，而第二季度為 28 億美元，增長了 20%。相比之下，去年第三季度虧損 2 億美元。

Diluted earnings per share for Q3 2021 were $7.70.

2021 年第三季度的稀釋後每股收益為 7.70 美元。

Turning now to year-to-date financial results compared to prior year on Slide 13. Total revenue was $11.3 billion for the first 9 months of this year compared to $0.2 billion for the same period in 2020. The significant growth was driven by the sales of 510 million doses of the company's COVID-19 vaccine.

現在轉向幻燈片 13 上與上一年相比的年初至今財務業績。今年前 9 個月的總收入為 113 億美元，而 2020 年同期為 2 億美元。銷售額的顯著增長該公司的 COVID-19 疫苗的 5.1 億劑。

Grant revenue of $473 million in the first 9 months of 2021, an increase of $286 million compared to the prior year was primarily driven by increases in revenue from BARDA related to the company's COVID-19 vaccine development. Cost of sales was $1.7 billion or 16% of the company's product sales for the year-to-date period as of September 30, including third-party royalties of $400 million.

2021 年前 9 個月的贈款收入為 4.73 億美元，比上年增加 2.86 億美元，主要是由於 BARDA 與公司 COVID-19疫苗開發相關的收入增加。截至 9 月 30 日，年初至今的銷售成本為 17 億美元，占公司產品銷售額的 16%，其中包括 4 億美元的第三方特許權使用費。

A portion of the inventory costs associated with this year's product sales was expensed as prelaunch inventory costs in 2020. If inventories sold for the first 9 months of this year was valued at cost, our cost of sales for the period would have been 17% of the product sales.

與今年產品銷售相關的部分庫存成本在 2020 年作為啟動前庫存成本計入費用。如果今年前 9 個月銷售的存貨按成本計價，我們在此期間的銷售成本將是 17%產品銷售。

Research and development expenses were $1.3 billion for the 9 months ended September 30 of this year compared to $0.6 billion for the same period in 2020. The growth in spending in 2021 was mainly due to increase in clinical trial expenses and to a lesser extent personnel-related costs, manufacturing expenses and consulting an outside services primarily driven by increased mRNA-1273 clinical development activities.

截至今年 9 月 30 日止 9 個月的研發費用為 13 億美元，而 2020 年同期為 6 億美元。2021 年支出的增長主要是由於臨床試驗費用的增加以及在較小程度上人事-相關成本、製造費用和諮詢外部服務主要受 mRNA-1273 臨床開發活動增加的推動。

Selling, general and administrative expenses were $0.4 billion for the first 9 months of this year compared to $0.1 billion for the same period in 2020. The growth in spending in 2021 was mainly due to increases in consulting and outside services, personnel-related costs and marketing expenses primarily attributable to the company's COVID-19 vaccine commercialization-related activities and increased headcount.

今年前 9 個月的銷售、一般和管理費用為 4 億美元，而 2020 年同期為 1 億美元。2021 年支出的增長主要是由於諮詢和外部服務、人事相關成本和營銷費用主要歸因於公司 COVID-19疫苗商業化相關活動和員工人數增加。

For the 9 months ended September 30, we recorded a provision for income taxes of $541 million compared to insignificant amounts in the same period in 2020. Our effective tax rate for the first 9 months of this year was 7%. it was lower than the U.S. statutory rate, primarily due to nonrecurring benefits related to the release of the valuation allowance, the ongoing benefit of the foreign-derived intangible income deduction as well as a discrete item for excess tax deductions related to stock-based compensation.

截至 9 月 30 日的 9 個月，我們記錄了 5.41 億美元的所得稅撥備，而 2020 年同期的數額微不足道。我們今年前 9 個月的有效稅率為 7%。它低於美國的法定稅率，主要是由於與釋放估值津貼相關的非經常性收益、來自外國的無形收入扣除的持續收益以及與股票補償相關的超額稅收扣除的離散項目.

Net income was $7.3 billion for the 9 months ended September 30 of this year, compared to a net loss of $0.5 billion for the same period in 2020. Diluted earnings per share were $17 for the first 9 months of 2021.

截至今年 9 月 30 日的 9 個月淨收入為 73 億美元，而 2020 年同期淨虧損 5 億美元。2021 年前 9 個月的每股攤薄收益為 17 美元。

Turning to cash and selected cash flow information on Slide 14. We ended Q3 2021 with cash and investments of $15.3 billion compared to $12.2 billion at the end of Q2. The increase is driven by our commercial sales and additional customer deposits received in the third quarter for future purchases of our COVID-19 vaccine.

轉向幻燈片 14 上的現金和選定的現金流信息。截至 2021 年第三季度，我們的現金和投資為 153 億美元，而第二季度末為 122 億美元。這一增長是由我們的商業銷售和第三季度收到的額外客戶押金推動的，用於未來購買我們的 COVID-19 疫苗。

Net cash provided by operating activities was $3.3 billion in Q3 after $4.1 billion in Q2. The quarter-over-quarter reduction is driven by a lower amount of cash deposits for future product supply received in Q3 compared to Q2.

第三季度經營活動提供的淨現金為 33 億美元，而第二季度為 41 億美元。與第二季度相比，第三季度收到的用於未來產品供應的現金存款減少了季度環比的減少。

On a year-to-date basis, net cash provided by operating activities was $10.3 billion compared to $0.8 billion in the prior year.

年初至今，經營活動提供的淨現金為 103 億美元，而去年為 8 億美元。

Cash used for purchases of property and equipment was $164 million for the 9 months ended September 30 compared to $44 million for the same period in 2020, reflecting continuous investments in our manufacturing infrastructure.

截至 9 月 30 日止 9 個月，用於購買物業和設備的現金為 1.64 億美元，而 2020 年同期為 4400 萬美元，反映了我們對製造基礎設施的持續投資。

Now turning to Slide 15. Let me briefly expand further on our cash and investment position and the net balance of cash deposits for future product supply, as this is an important point when modeling future cash flows. The cash and investment balance reported as of September 30 was $15.3 billion, up from $12.2 billion as of June 30. The increase is driven by our commercial activities, including cash receipts from product sales and customer deposits for future product supply. The net balance cash deposits for future product supply was $6.7 billion at the end of Q3 at the similar level to the balance in Q2 of this year.

現在轉到幻燈片 15。讓我簡要地進一步擴展我們的現金和投資頭寸以及未來產品供應的現金存款淨餘額，因為這是對未來現金流建模的一個重要點。截至 9 月 30 日報告的現金和投資餘額為 153 億美元，高於 6 月 30 日的 122 億美元。這一增長是由我們的商業活動推動的，包括產品銷售的現金收入和用於未來產品供應的客戶存款。截至第三季度末，未來產品供應的現金存款淨餘額為 67 億美元，與今年第二季度的餘額相近。

Turning now to the 2021 updated financial framework on Slide 16. For the full year 2021, we expect a product sales range of $15 billion to $18 billion. We now expect to be able to deliver 700 million to 800 million doses at the 100-microgram dose level to our customers. This compares to the prior outlook of 800 million to 1 billion doses.

現在轉向幻燈片 16 上的 2021 年更新財務框架。對於 2021 年全年，我們預計產品銷售額範圍為 150 億美元至 180 億美元。我們現在預計能夠以 100 微克劑量水平向我們的客戶提供 7 億至 8 億劑劑量。相比之下，之前的預期為 8 億至 10 億劑。

Our total cost of sales includes the cost of goods manufactured, third-party royalties as well as logistics and warehousing costs. Given the favorability we have observed in the year-to-date period, we now expect total cost of sales as a percent of product sales between 16% to 17% for the full year 2021. This compares to our previous outlook of 18% to 20% of product sales.

我們的總銷售成本包括商品製造成本、第三方特許權使用費以及物流和倉儲成本。鑑於我們在年初至今觀察到的有利情況，我們現在預計 2021 年全年總銷售成本佔產品銷售額的百分比在 16% 至 17% 之間。相比之下，我們之前的預測為 18% 至產品銷售額的 20%。

For 2022, we currently expect the cost of sales ratio to exceed 20%,driven by customer mix and multiple presentation types.

到 2022 年，我們目前預計銷售成本比率將超過 20%，受客戶組合和多種展示類型的推動。

On the R&D and SG&A expense side, we continue to plan for an increase on a quarter-over-quarter basis and expect this trend to continue for the remainder of 2021 and beyond driven by a maturing development portfolio and the scale-up of our commercial activities.

在研發和 SG&A 費用方面，我們繼續計劃在季度環比的基礎上增加，並預計這一趨勢將在 2021 年剩餘時間及以後繼續，這是由於成熟的開發組合和我們商業規模的擴大活動。

Based on further increased visibility of the utilization of our accumulated net operating loss carryforward, expected global sales mix and the mentioned discrete benefits in the first 9 months of this year, we now expect our all-in 2021 tax rate to be in the high single-digit range. This compares to our previous forecast of approximately 10%.

基於對我們累計淨營業虧損結轉利用、預期全球銷售組合以及今年前 9 個月上述離散收益的進一步提高的可見性，我們現在預計我們 2021 年的全部稅率將處於高單-數字範圍。相比之下，我們之前的預測約為 10%。

Since we won't have a material benefit from our valuation allowance in future years, we expect our reported 2022 effective tax rate will increase relative to our 2021 rate. It's also too early to further comment on impacts from a potential tax reform.

由於我們在未來幾年不會從我們的估值津貼中獲得實質性利益，我們預計我們報告的 2022 年有效稅率將相對於我們 2021 年的稅率增加。現在進一步評論潛在稅制改革的影響還為時過早。

Finally, regarding capital investments. We are now planning for approximately $0.4 billion of capital investment to fall into the 2021 calendar year compared to our previous range of $450 million to $550 million. We are strongly committed to a further build-out of our manufacturing and general company infrastructure and hence, predict capital investment in 2022 will be meaningfully above 2021 levels.

最後，關於資本投資。我們現在計劃在 2021 日曆年投入約 4 億美元的資本投資，而我們之前的投資範圍為 4.5 億美元至 5.5 億美元。我們堅定地致力於進一步建設我們的製造和一般公司基礎設施，因此預測 2022 年的資本投資將顯著高於 2021 年的水平。

This concludes my remarks concerning the financial performance, and I now turn the call over to Paul Burton.

我對財務業績的評論到此結束，我現在將電話轉給 Paul Burton。

Thank you, David, and good morning, good afternoon, everyone.

謝謝你，大衛，大家早上好，下午好。

With more than 150 million people worldwide now having received 2 doses of our vaccine, we are humbled to be able to see the positive impact it is having on people's lives around the world. We are reminded of the fact that almost 250 million people have been infected with COVID-19 globally and 5 million people have lost their lives. Our profound thanks, as always, go out to those on the front lines, working tirelessly to keep us safe in this ongoing fight.

現在全世界有超過 1.5 億人接種了 2 劑我們的疫苗，我們很榮幸能夠看到它對世界各地人們的生活產生的積極影響。我們想起這樣一個事實，全球有近 2.5 億人感染了 COVID-19，500 萬人喪生。我們一如既往地向前線的人們表示深深的感謝，他們在這場持續的戰鬥中不知疲倦地工作以確保我們的安全。

Through numerous independent studies, time and time again, we see consistent findings showing that mRNA-1273 is highly effective in saving lives, reducing hospitalizations and reducing the risk of COVID-19 infection. I will highlight a few of these independently conducted studies this morning.

通過大量獨立研究，我們一次又一次地看到一致的結果表明 mRNA-1273 在挽救生命、減少住院和降低 COVID-19 感染風險方面非常有效。今天早上我將重點介紹其中一些獨立進行的研究。

In Slide 18, I will begin with some of the data from the United States government. These data come from the CDC and show through September of this year, the difference in COVID-19 cases between fully vaccinated and unvaccinated populations. An unvaccinated person has an 11-fold greater risk of dying from COVID-19 underscoring the importance of getting vaccinated plays in our protection and ending this pandemic.

在幻燈片 18 中，我將從美國政府的一些數據開始。這些數據來自 CDC，並顯示了截至今年 9 月，完全接種疫苗和未接種疫苗的人群之間的 COVID-19 病例差異。未接種疫苗的人死於 COVID-19 的風險要高出 11 倍，這凸顯了接種疫苗對我們的保護和結束這一流行病的重要性。

The data showed that vaccination with mRNA-1273 provides the greatest protection, not only against COVID-19 infection, but also death due to COVID-19. In fact, even during the surge of the Delta virus variant during the summer months this year, Moderna's vaccine had the lowest reported deaths associated with breakthrough infection as the CDC data demonstrated.

數據顯示，用 mRNA-1273 接種疫苗可提供最大的保護，不僅可以防止 COVID-19 感染，還可以防止因 COVID-19 導致的死亡。事實上，即使在今年夏季 Delta 病毒變種激增期間，正如 CDC 數據所顯示的那樣，Moderna 的疫苗報告的與突破性感染相關的死亡人數最少。

Approximately 160 million doses of the Moderna vaccine have been administered in the United States. And in the next slide, I want to show you some further government-generated data in a country where the Moderna vaccine has also had extensive use and that country is Switzerland.

美國已經接種了大約 1.6 億劑 Moderna 疫苗。在下一張幻燈片中，我想向你們展示一些政府生成的更多數據，這些數據來自一個 Moderna 疫苗也被廣泛使用的國家，而那個國家就是瑞士。

You can see here exposure data on the left. Approximately 3.6 million people have been fully vaccinated with the Moderna vaccine and 1.9 million people have been fully vaccinated with the Pfizer BionTech vaccine.

您可以在此處查看左側的曝光數據。大約 360 萬人已經完全接種了 Moderna 疫苗，190 萬人已經完全接種了輝瑞 BionTech 疫苗。

These government-generated data from the Federal Office of Public Health in Switzerland, again, are clear and showed that vaccination with the Moderna vaccine is highly effective at reducing infections, hospitalizations and deaths due to COVID-19 infection.

這些來自瑞士聯邦公共衛生辦公室的政府生成數據再次明確表明，使用 Moderna 疫苗接種疫苗在減少因 COVID-19 感染引起的感染、住院和死亡方面非常有效。

For every 1 million people vaccinated use of mRNA-1273 would be expected to result in 643 fewer COVID-19 breakthrough infections, 78 hospitalizations and 38 fewer deaths.

對於每 100 萬人接種 mRNA-1273，預計將減少 643 人的 COVID-19 突破性感染、78 人住院和 38 人死亡。

Next, in Slide 20, our data from 2 other recent independent studies that build on the results I just showed you from Switzerland. The first study on the left side of this slide, followed 38 million vaccinated people in the United States, Iceland and South Korea. And again, found that those people vaccinated with mRNA-1273 were at 53% reduced risk of a COVID-19 infection and 33% reduced risk of a COVID-19 hospitalization compared to those vaccinated with the alternate mRNA vaccine.

接下來，在幻燈片 20 中，我們的數據來自其他兩項最近的獨立研究，這些研究基於我剛剛在瑞士向您展示的結果。這張幻燈片左側的第一項研究跟踪了美國、冰島和韓國的 3800 萬接種疫苗的人。再次發現，與接種替代 mRNA 疫苗的人相比，接種 mRNA-1273 的人感染 COVID-19 的風險降低了 53%，住院的風險降低了 33%。

The data on the right hand of the slide are from a recent publication by Nordstrom and colleagues in Sweden and Norway, showing that mRNA-1273 delivered 87% vaccine effectiveness during a time of high Delta variant circulation in those countries.

幻燈片右側的數據來自瑞典和挪威的 Nordstrom 及其同事最近發表的一篇文章，顯示 mRNA-1273 在這些國家的 Delta 變異高流通期間提供了 87% 的疫苗有效性。

The data I've shared so far are all from the general population. Let me turn now to the effectiveness of the Moderna vaccine, in particularly vulnerable populations the immunocompromised. These data were published just 2 days ago, again, by the United States CDC vision network and examine vaccine effectiveness at preventing COVID-19 hospitalization, which is so critically important in individuals with a variety of immunocompromised medical conditions between January and September of this year.

到目前為止我分享的數據都來自普通人群。現在讓我談談 Moderna 疫苗的有效性，尤其適用於免疫功能低下的脆弱人群。這些數據於 2 天前再次由美國 CDC 視覺網絡發布，並檢查疫苗在預防 COVID-19 住院方面的有效性，這對於今年 1 月至 9 月期間患有各種免疫功能低下疾病的個體至關重要.

As the authors of this study note, with the exception of those individuals with rheumatic disorders, vaccine effective point estimates were generally higher for the Moderna vaccine than for the Pfizer/BioNTech vaccine and the difference in effectiveness in these hard to immunize populations is shown in the column on the right.

正如本研究的作者所指出的，除了那些患有風濕性疾病的個體外，Moderna 疫苗的疫苗有效點估計值通常高于輝瑞/BioNTech 疫苗，並且這些難以免疫的人群中的有效性差異顯示在右側的列。

I want to turn now to the topic of myocarditis and to put it in the context of the clinical benefits of vaccination that I've just described with mRNA-1273. It is important to recognize that the cases of myocarditis reported to occur following mRNA vaccination of rare, generally mild, typically respond to conservative treatment and self-limiting. Health authorities have reviewed many data sets and the U.S. CDC and WHO have concluded that there is risk of myocarditis and pericarditis after receiving any mRNA vaccine. The WHO's Advisory Committee on vaccine safety notes that myocaditis can occur following SARS-CoV-2 infection or COVID-19 disease and that mRNA vaccines have a clear benefit in preventing hospitalization and death from COVID-19.

我現在想談談心肌炎這個話題，並將它放在我剛剛用 mRNA-1273 描述的疫苗接種的臨床益處的背景下。重要的是要認識到，據報導，心肌炎病例發生在罕見的、通常輕微的 mRNA 疫苗接種後，通常對保守治療和自限性有反應。衛生當局審查了許多數據集，美國疾病預防控制中心和世界衛生組織得出結論，接受任何 mRNA 疫苗後存在心肌炎和心包炎的風險。世衛組織疫苗安全諮詢委員會指出，心肌炎可能發生在 SARS-CoV-2 感染或 COVID-19 疾病之後，並且 mRNA 疫苗在預防 COVID-19 住院和死亡方面具有明顯的益處。

Analysis from our global safety database show that the events of myocarditis are very rare. Overall, we observed 9.5 cases of myocarditis per million vaccinated individuals compared to an expected rate of 21 cases per million individuals.

我們全球安全數據庫的分析表明，心肌炎事件非常罕見。總體而言，我們觀察到每百萬接種疫苗的人中有 9.5 例心肌炎，而預期的發病率為每百萬人 21 例。

Now in common with other reports of mRNA vaccines in individuals aged 18 to 24, we see an increased rate of myocarditis of 40 cases versus 17 expected cases per million individuals. These data from our own safety database are consistent with the findings from safety databases evaluated by the CDC and other global health authorities. And the link to the CDC analysis is provided on the slide below.

現在與 18 至 24 歲個體中 mRNA 疫苗的其他報告相同，我們看到每百萬人中 40 例心肌炎的發病率高於預期的 17 例。這些來自我們自己的安全數據庫的數據與 CDC 和其他全球衛生當局評估的安全數據庫的結果一致。下面的幻燈片提供了 CDC 分析的鏈接。

MRNA-1273 has been authorized for use in adolescents, aged 12 to 18 in multiple countries around the world. Moderna's global safety database has information on an estimated 1.5 million of them, providing us an opportunity to look at the rate of myocarditis in those individuals and those data are shown in this table. We see the small absolute well-described risk of increased myocarditis rates in males aged 18 to 24 that I just described to you. But we do not see an increased risk in adolescents neither in boys nor in girls. These data are reassuring and important as we continue to offer mRNA-1273 to adults, adolescents and as we file for authorization in children.

MRNA-1273 已獲准在世界多個國家用於 12 至 18 歲的青少年。 Moderna 的全球安全數據庫中估計有 150 萬人的信息，這使我們有機會了解這些人的心肌炎發病率，這些數據顯示在此表中。我們看到我剛剛向您描述的 18 至 24 歲男性心肌炎發病率增加的絕對風險很小。但我們沒有看到青少年的風險增加，無論是男孩還是女孩。隨著我們繼續向成人、青少年提供 mRNA-1273 以及我們為兒童申請授權，這些數據令人放心且重要。

So in summary, the data I've shared with you today from independent government reports in the United States and in Switzerland, countries with high vaccination rates of Moderna's vaccine showed mRNA-1273 is associated with lowest breakthrough infections, hospitalizations and deaths due to COVID-19. Other independent studies in millions of individuals continue to show that mRNA-1273 is highly effective in reducing the risk of breakthrough COVID-19 as well as hospitalizations and death. And importantly, this is also true in those vulnerable and hard to vaccinate immunocompromised patient populations.

總而言之，我今天與您分享的數據來自美國和瑞士的獨立政府報告，Moderna 疫苗接種率高的國家顯示 mRNA-1273 與 COVID 引起的最低突破性感染、住院和死亡有關-19。對數百萬人進行的其他獨立研究繼續表明，mRNA-1273 在降低突破性 COVID-19 以及住院和死亡的風險方面非常有效。重要的是，對於那些易受感染且難以接種免疫功能低下的患者群體也是如此。

Moderna's global safety database of 151 million vaccinated individuals shows a rate of myocarditis in males aged 18 to 24 that is consistent with analysis by CDC and others. Moderna's global safety database does not show an increased risk of myocarditis in 1.5 million individuals below the age of 18 and vaccinated with Spikevax.

Moderna 的全球安全數據庫包含 1.51 億接種疫苗的個體，顯示 18 至 24 歲男性的心肌炎發病率與 CDC 和其他機構的分析一致。 Moderna 的全球安全數據庫並未顯示 150 萬 18 歲以下接種 Spikevax 疫苗的人患心肌炎的風險增加。

So these -- this concludes my quick overview of some recent analyses of mRNA-1273 effectiveness data and review of data from our global safety database. And I will now turn the call over to Stephen.

所以這些 - 這結束了我對最近對 mRNA-1273 有效性數據的一些分析和對我們全球安全數據庫數據的審查的快速概述。我現在將把電話轉給斯蒂芬。

Thank you, Paul, and good morning or good afternoon, everyone. Today, I'll review the progress we've made across our vaccines and therapeutics pipeline.

謝謝你，保羅，大家早上好或下午好。今天，我將回顧我們在疫苗和治療產品線上取得的進展。

Let me start with our COVID-19 vaccine, mRNA-1273, for adult ages 18 and above, where there are a number of important regulatory updates.

讓我從我們針對 18 歲及以上成人的 COVID-19 疫苗 mRNA-1273 開始，其中有許多重要的監管更新。

First, we have announced that the FDA granted priority review to Moderna's COVID-19 vaccine BLA.

首先，我們宣布 FDA 對 Moderna 的 COVID-19疫苗 BLA 給予優先審查。

In October, we also received an EUA from the FDA and the European Commission's approval for a booster dose of our COVID-19 vaccine at the 50-microgram dose level for the adult cohort, ages 18 and above.

10 月，我們還收到了 FDA 的 EUA 和歐盟委員會的批准，為 18 歲及以上的成人群體提供 50 微克劑量水平的 COVID-19 疫苗加強劑量。

Turning to the adolescents and pediatric settings. As a reminder, there are 2 clinical trials for each of these groups: TeenCOVE is our study in the adolescent population, 12 to 17 year olds; and KidCove is the study in the pediatric population, age 11 and younger. For the adolescent population, 12 to 17 years old, our vaccine is authorized in a number of countries worldwide, including the United Kingdom, the European Union, Canada, Switzerland, Japan, Thailand, Taiwan, Saudi Arabia and Argentina to name a few.

轉向青少年和兒科環境。提醒一下，每個組都有 2 項臨床試驗：TeenCOVE 是我們針對 12 至 17 歲青少年人群的研究； KidCove 是一項針對 11 歲及以下兒童人群的研究。對於 12 至 17 歲的青少年群體，我們的疫苗已在全球多個國家/地區獲得授權，包括英國、歐盟、加拿大、瑞士、日本、泰國、台灣、沙特阿拉伯和阿根廷等。

We've submitted data from our KidCove study to the FDA in the United States as well as to other countries. We're recently notified by the FDA that the agency will require additional time to evaluate our proposed amendment due to recent analysis of the risk of myocarditis after vaccination in some populations. The agency expects this evaluation may extend until January 2022.

我們已將 KidCove 研究的數據提交給美國和其他國家的 FDA。 FDA 最近通知我們，由於最近對某些人群接種疫苗後心肌炎風險的分析，該機構將需要更多時間來評估我們提出的修正案。該機構預計該評估可能會延長至 2022 年 1 月。

As Paul noted, Moderna's global safety database includes an estimated 1.5 million adolescents, who received the Moderna COVID-19 vaccine, most outside of the United States. And to date, we have not observed a rate of myocarditis from those younger than 18 years in our safety database that points to an increased risk of myocarditis in that population. We continue to believe the benefits of vaccination significantly outweigh the risks.

正如保羅所指出的，Moderna 的全球安全數據庫包括估計有 150 萬青少年接種了 Moderna COVID-19 疫苗，其中大部分在美國以外。迄今為止，我們尚未在我們的安全數據庫中觀察到 18 歲以下人群的心肌炎發病率表明該人群患心肌炎的風險增加。我們仍然相信接種疫苗的好處遠大於風險。

In the pediatric setting, our study known as KidCove is ongoing and is focused in 3 age groups, a group with children 6 to 11 years of age; a group of 2 to less than 6; and a group of children 6 months to less than 2. The trial consists of a dose escalation phase for each group, followed by an expansion phase once the dose has been selected.

在兒科環境中，我們被稱為 KidCove 的研究正在進行中，主要針對 3 個年齡組，即 6 至 11 歲兒童組； 2人至6人以下的一組；和一組 6 個月至 2 個月以下的兒童。該試驗包括每組的劑量遞增階段，一旦選擇了劑量，則隨後是擴展階段。

Last week, we shared positive top line data from the oldest of the age groups in KidCove, the 6- to 11-year-old cohort, showing the 250-microgram doses of mRNA-1273 were generally well tolerated and that the primary immunogenicity endpoints were met.

上週，我們分享了 KidCove 中年齡最大的年齡組（6 至 11 歲的隊列）的陽性頂線數據，顯示 250 微克劑量的 mRNA-1273 通常具有良好的耐受性，並且主要免疫原性終點遇到了。

We will submit our results soon to the EMA and other global regulatory agencies.

我們將很快將我們的結果提交給 EMA 和其他全球監管機構。

For the other 2 age groups in KidCove, the 2 to less than 6 years old group and the 6-month to less than 2-year old group, our dose selection studies are ongoing.

對於 KidCove 的其他 2 個年齡組，即 2 至 6 歲以下組和 6 個月至 2 歲以下組，我們的劑量選擇研究正在進行中。

On the next slide, let me share with you some of the data we have in children ages 6 to less than 12 years of age. This data is after dose 1 as we are waiting for additional follow-up time to share the post-dose 2 data. As a reminder, the study was randomized 2:1 for vaccine versus placebo.

在下一張幻燈片上，讓我與您分享一些我們在 6 至 12 歲以下兒童中獲得的數據。該數據是在第 1 劑之後，因為我們正在等待額外的隨訪時間來分享第 2 劑後的數據。提醒一下，該研究是按 2:1 隨機分配疫苗與安慰劑的。

Based on the case definition of COVID-19 that we used in the Phase III adult study, the observed interim vaccine efficacy was 100% in this analysis, starting 2 weeks after the first dose and using that case definition.

根據我們在 III 期成人研究中使用的 COVID-19 病例定義，在該分析中觀察到的臨時疫苗效力為 100%，從第一次接種後 2 週開始並使用該病例定義。

Vaccine efficacy against SARS-CoV-2 infection was also high at 80%, and vaccine efficacy against symptom -- asymptomatic SARS-CoV-2 infection was 65%. Both endpoints that we think are incredibly important as we seek to end the pandemic.

疫苗對 SARS-CoV-2 感染的有效性也高達 80%，疫苗對症狀-無症狀 SARS-CoV-2 感染的有效性為 65%。在我們尋求結束大流行的過程中，我們認為這兩個端點都非常重要。

Turning now to our booster and next-generation COVID-19 vaccine programs on Slide 28. As a reminder, we are evaluating multiple COVID-19 vaccines as potential boosters to provide the broadest range of countermeasures to the virus, as it continues to evolve. We were granted EUA for the 50-microgram dose of our current vaccine as a booster, as mentioned previously. And we are currently evaluating 2 variant-specific vaccines and 2 multivalent vaccine candidates, which are combinations of different variants of concern in an effort to stay ahead of the evolving virus.

現在轉到幻燈片 28 上的加強和下一代 COVID-19 疫苗計劃。提醒一下，隨著病毒的不斷發展，我們正在評估多種 COVID-19 疫苗作為潛在的加強劑，以提供最廣泛的應對病毒的措施。如前所述，我們獲得了 50 微克劑量的當前疫苗作為加強劑的 EUA。我們目前正在評估 2 種變體特異性疫苗和 2 種多價候選疫苗，它們是不同變體的組合，以努力領先於不斷發展的病毒。

In addition, we're also evaluating mRNA-1283 as a next-generation refrigerator stable vaccine, which is in a Phase I study. The interim analysis of that Phase I data has been completed at 3 different dose levels and indicates that a lower dose of mRNA-1283 can achieve similar neutralizing antibody responses as a primary -- in primary series as our authorized vaccine mRNA-1273.

此外，我們還在評估 mRNA-1283 作為下一代冰箱穩定疫苗，該疫苗處於 I 期研究中。該 I 期數據的中期分析已在 3 個不同劑量水平下完成，並表明較低劑量的 mRNA-1283 可以實現與初級系列類似的中和抗體反應——在初級系列中作為我們授權的疫苗 mRNA-1273。

mRNA-1283 also had an acceptable safety and tolerability profile and we're moving forward towards a Phase II booster study for that candidate. This will also evaluate even lower doses of mRNA-1283 given the strong boosting performance seen in Phase I.

mRNA-1283 也具有可接受的安全性和耐受性，我們正在推進對該候選人的 II 期加強研究。鑑於在第一階段看到的強大的促進性能，這也將評估更低劑量的 mRNA-1283。

While the start of our booster strategy in late January of this year was in response to the threat of newly identified variants at that time, our booster strategy has continued to evolve as the pandemic unfolds.

雖然我們在今年 1 月下旬開始加強戰略是為了應對當時新發現的變異的威脅，但隨著大流行的蔓延，我們的加強戰略仍在繼續發展。

Slide 29 is a slide we shared at our Vaccines Day in April of this year. At the time, the graph on the left was illustrative of our view of the likely path for the pandemic, based on our perspective on respiratory virus evolution and epidemiology, including prior coronavirus pandemics.

幻燈片 29 是我們在今年 4 月的疫苗日分享的一張幻燈片。當時，左側的圖表說明了我們對大流行的可能路徑的看法，這是基於我們對呼吸道病毒進化和流行病學的看法，包括之前的冠狀病毒大流行。

Today, it's becoming clear that the SARS-CoV-2 virus is following the footsteps of other respiratory viruses, and is on its way to becoming a seasonal epidemic/endemic threat.

今天，越來越明顯的是，SARS-CoV-2 病毒正在追隨其他呼吸道病毒的腳步，並且正在成為季節性流行病/地方病威脅。

So where are we now? With Delta and the potential for other variants, the winter of 2021, 2022 still looks to be a time of moderating but persistent variant epidemic waves. Infection and reinfection continue to cause morbidity and mortality during this phase, but hopefully in fewer people. The focus will remain on suppressing the rate of viral evolution and emergence. Primary vaccination is critical.

那麼我們現在在哪裡？鑑於 Delta 和其他變種的潛力，2021 年冬天，2022 年看起來仍然是一個緩和但持續的變種流行浪潮的時期。在此階段，感染和再感染繼續導致發病率和死亡率，但希望在更少的人中。重點仍將放在抑制病毒進化和出現的速度上。初級疫苗接種至關重要。

But given the high rate of background transmission, booster vaccines will also be important in all countries.

但鑑於背景傳播率很高，加強疫苗在所有國家也很重要。

Looking ahead, we expect 2022 will be the beginning of the seasonal endemic phase, reinfections in individuals who are at high risk, including older adults, the immunocompromised or healthy adults with more rapidly waning immunity due to under vaccination with potentially less effective vaccines will be at the greatest risk for severe outcomes.

展望未來，我們預計 2022 年將是季節性流行階段的開始，高風險個體（包括老年人、免疫功能低下或健康的成年人）的再感染率將因疫苗接種不足而迅速減弱。面臨嚴重後果的最大風險。

As with the recent Delta wave, this will include some risk of hospitalization and unfortunately, some risk of death as well as social disruption. We believe this will become the primary population for whom seasonal boosting will provide a significant enduring benefit.

與最近的三角洲浪潮一樣，這將包括一些住院風險，不幸的是，還有一些死亡風險以及社會混亂。我們相信，這將成為主要人群，季節性增強將為他們帶來顯著的持久利益。

In summary, as we described earlier this year, we believe SARS-CoV-2 is following a familiar path that will ultimately become a seasonal threat to a large population of higher risk adults. Perhaps the biggest unknown in the near term is the extent to which further viral evolution in the coming Northern Hemisphere winter and Southern Hemisphere winter in 2022 will create hurdle ground for new -- newly transmissible and immune-evading variants to emerge. If so, rapid boosting may become necessary.

總之，正如我們今年早些時候所描述的，我們相信 SARS-CoV-2 正在走一條熟悉的道路，最終將成為對大量高風險成年人的季節性威脅。也許近期最大的未知數是即將到來的北半球冬季和 2022 年南半球冬季的病毒進一步進化將在多大程度上為新的 - 新傳播和免疫逃避變體的出現創造障礙。如果是這樣，可能需要快速提升。

We will need to remain vigilant throughout this time as we fight the pandemic, and we are ready to advance updated boosters rapidly if they become needed.

在抗擊這一流行病的過程中，我們將需要在整個這段時間內保持警惕，並且我們準備好在需要時迅速推進更新的助推器。

Now moving from COVID onto Slide 30. We announced in September that the Phase I portion of our quadrivalent seasonal flu vaccine, mRNA-1010, is fully enrolled, and we look forward to sharing data from that trial and moving to Phase II soon.

現在從 COVID 轉到幻燈片 30。我們在 9 月宣布，我們的四價季節性流感疫苗 mRNA-1010 的第一階段部分已完全註冊，我們期待分享該試驗的數據並很快進入第二階段。

We also announced positive Phase I interim data from our RSV vaccine in older adults in September, and we plan to start pivotal Phase II/III RSV vaccine trial before the end of 2021.

我們還於 9 月公佈了我們的 RSV 疫苗在老年人中的 I 期中期數據，我們計劃在 2021 年底之前開始關鍵的 II/III 期 RSV 疫苗試驗。

Separately, the pediatric RSV program continues to move forward with cohorts enrolling well in our Phase I study.

另外，兒科 RSV 計劃繼續向前推進，隊列在我們的 I 期研究中登記良好。

Our hMPV/PIV3 study in pediatrics is also currently enrolling in toddlers.

我們在兒科的 hMPV/PIV3 研究目前也在招募幼兒。

We were very excited to announce last week that our Phase III CMV vaccine trial has dosed its first participants. The start of the Phase III trial, CMV -- CMVictory is an important step in evaluating our CMV vaccine against congenital CMV.

上週，我們非常高興地宣布，我們的 III 期 CMV 疫苗試驗已經給第一批參與者接種了疫苗。第三階段試驗的開始，CMV——CMVictory 是評估我們的 CMV 疫苗對抗先天性 CMV 的重要一步。

As a reminder, CMV is the #1 cause of birth defects in the United States, and we are evaluating the safety and efficacy of mRNA-1647 in women ages 16 to 40 at the 100-microgram dose level. The trial is starting in the U.S. and will include approximately 150 sites globally, and will enroll on approximately 6,900 women of child-bearing age. Importantly, including criteria of the trial includes women at high risk of CMV exposure through direct exposure in the home, socially or occupationally to children under 5 years of age.

提醒一下，CMV 是美國出生缺陷的第一大原因，我們正在評估 mRNA-1647 在 100 微克劑量水平下對 16 至 40 歲女性的安全性和有效性。該試驗在美國開始，將包括全球約 150 個地點，並將招募約 6,900 名育齡婦女。重要的是，包括試驗的標準包括通過在家中、社會或職業上直接暴露於 5 歲以下兒童的 CMV 暴露高風險的女性。

Diversity in our clinical trials is also extremely important to us, and we're proud to continue our commitment from last year on clinical trial diversity. We believe setting targets and measuring ourselves against them remains one of the most important ways we can work to address the health care inequity in clinical research.

我們臨床試驗的多樣性對我們來說也極為重要，我們很自豪能夠繼續從去年開始就臨床試驗多樣性做出承諾。我們相信，設定目標並根據目標衡量自己仍然是我們解決臨床研究中醫療保健不公平問題的最重要方法之一。

For the CMVictory Phase III study, our goal is to have 42% of the trial participants in the United States come from communities of color, many of which are disproportionately impacted by the CMV virus.

對於 CMVictory III 期研究，我們的目標是讓美國 42% 的試驗參與者來自有色人種社區，其中許多人受到 CMV 病毒的嚴重影響。

Moving on from vaccines. This slide highlights our mRNA therapeutics pipeline. At R&D Day, we described how our modalities and therapeutic areas overlap.

從疫苗開始。這張幻燈片突出了我們的 mRNA 治療管道。在研發日，我們描述了我們的模式和治療領域是如何重疊的。

In oncology, our PCV Phase II trial is now fully enrolled, and we expect to readout for that as early as the fourth quarter of next year.

在腫瘤學方面，我們的 PCV II 期試驗現已全部註冊，我們預計最早將於明年第四季度公佈。

Separately, an expansion cohort in head and neck cancer in our Phase I trial is ongoing. We also have Phase I trials ongoing for our KRAS vaccine, which is partnered with Merck, the triplet program; and the IL-12 intratumoral program, which is partnered with AstraZeneca.

另外，在我們的 I 期試驗中，頭頸癌的擴展隊列正在進行中。我們還與默克公司合作開展了 KRAS 疫苗的 I 期試驗，三聯疫苗；以及與阿斯利康合作的 IL-12 腫瘤內計劃。

In cardiovascular, our VEGF program, is also partnered with AstraZeneca, has completed the enrollment of a low-dose cohort in its Phase II study and AZ will be providing updates at a presentation of the data at the American Heart Association meeting in 2 weeks.

在心血管領域，我們的 VEGF 項目也與阿斯利康合作，已經完成了在其 II 期研究中的低劑量隊列的註冊， AZ 將在 2 週後的美國心臟協會會議上公佈數據時提供更新。

Within autoimmune, our IL-2 program is in a Phase I trial in dosing. And within rare diseases, our PA and MMA trials are ongoing in Phase I, and our GSD1a program has an open IND and is expected to start a Phase I study soon. I'm also very excited to announce that our first cystic fibrosis program has moved into preclinical development with IND enabling studies now underway. We and our partners at Vertex are pleased to announce that development candidate, VXc-522.

在自身免疫方面，我們的 IL-2 計劃處於 I 期給藥試驗。在罕見病領域，我們的 PA 和 MMA 試驗正在進行 I 期，我們的 GSD1a 項目有一個開放的 IND，預計將很快開始 I 期研究。我也很高興地宣布，我們的第一個囊性纖維化項目已進入臨床前開發階段，IND 研究正在進行中。我們和 Vertex 的合作夥伴很高興地宣布開發候選產品 VXc-522。

This program marks our first program in a brand-new modality inhaled therapeutics. As a reminder, Moderna modality encompasses a new method for utilizing our proprietary lipid nanoparticle technologies and mRNA technologies to bring forward medicines.

該計劃標誌著我們在全新方式吸入療法中的第一個計劃。提醒一下，Moderna 模式包括一種利用我們專有的脂質納米顆粒技術和 mRNA 技術來開發藥物的新方法。

Now double-clicking for a moment on the CF programs in research. Recall that we have 2 partnerships with Vertex. Our first collaboration targets the CFTR protein in trying to produce it using mRNA and LNP technologies. This is where we are advancing our candidate, VXc-522.

現在雙擊研究中的 CF 程序。回想一下，我們與 Vertex 有 2 個合作夥伴關係。我們的第一次合作針對 CFTR 蛋白，試圖使用 mRNA 和 LNP 技術生產它。這就是我們正在推進我們的候選人 VXc-522 的地方。

We also have a collaboration with Vertex using mRNA for gene editing and gene therapy. Both collaborations are focused on treating this 10% of CF patients with disease that unfortunately is not addressable with current CFTR modulators.

我們還與 Vertex 合作，使用 mRNA 進行基因編輯和基因治療。兩項合作都專注於治療這 10% 的 CF 患者，不幸的是，目前的 CFTR 調節劑無法解決這些疾病。

For this 10% of the CF population, alternative purchase are absolutely necessary. And the exciting update today, as I said a moment ago, is that we're announcing the first development candidate to move into development from that collaboration described on the left-hand side of this slide.

對於這 10% 的 CF 人口，絕對有必要進行替代購買。正如我剛才所說，今天令人興奮的更新是，我們將宣布第一個開發候選者從本幻燈片左側描述的協作進入開發。

In this collaboration, we're delivering messenger RNA that encodes for CFTR protein that is missing or nonfunctional in patients who suffer from cystic fibrosis. We plan to target that 10% that I mentioned a moment ago.

在這次合作中，我們提供了編碼 CFTR 蛋白的信使 RNA，該蛋白在患有囊性纖維化的患者中缺失或無功能。我們計劃以我剛才提到的那 10% 為目標。

We've been working incredibly hard with Vertex to advance the candidate, and we are very excited that, that has now moved into IND-enabling studies. As Vertex announced recently, they expect to submit an IND in 2022, paving the path for clinical studies in these patients.

我們一直在與 Vertex 一起努力推進候選人的發展，我們對此感到非常興奮，現在已經進入了支持 IND 的研究。正如 Vertex 最近宣布的那樣，他們預計將在 2022 年提交 IND，為這些患者的臨床研究鋪平道路。

In the close, I'd like to just highlight our pipeline on the following 3 lines, starting on Slide 35, which includes our respiratory vaccines in development. Slide 36 summarizes our large portfolio of latent virus vaccines and vaccines against other viruses. And on Slide 37, you will see the extensive mRNA therapeutics pipeline that we have in development.

最後，我想強調一下我們在以下 3 條線上的管道，從幻燈片 35 開始，其中包括我們正在開發的呼吸道疫苗。幻燈片 36 總結了我們大量的潛伏病毒疫苗和針對其他病毒的疫苗。在幻燈片 37 上，您將看到我們正在開發的廣泛的 mRNA 治療管道。

With that, I'll hand it back to Stephane to close.

有了這個，我會把它交還給 Stephane 關閉。

Thank you, Stephen. Slide 39 is from September 9 R&D Day and summarizes the product franchise we focus on at Moderna.

謝謝你，斯蒂芬。幻燈片 39 來自 9 月 9 日的研發日，總結了我們在 Moderna 關注的產品專營權。

Priority #1 is our pan-respiratory annual boost of franchise.

優先事項 #1 是我們的泛呼吸年度特許經營權提升。

Priority #2 is our first in-class vaccines for latent viruses.

優先事項 #2 是我們針對潛伏病毒的首個同類疫苗。

Priority #3 is our therapeutics based on mRNA-encoded proteins.

優先事項 #3 是我們基於 mRNA 編碼蛋白質的治療方法。

And Priority #4 is the therapeutic space on mRNA-encoded gene editing enzymes.

優先事項 #4 是 mRNA 編碼的基因編輯酶的治療空間。

As we have said for several quarters now, SARS-CoV-2 is here to stay and will evolve from a pandemic to endemic setting. We believe that 2022 will see pandemic in low-income countries throughout the year, but at high income countries, the year would be of 2 halves, pandemic priming for children and boosting for others with an endemic boosting campaign in the fall of '22.

正如我們已經說過幾個季度的那樣，SARS-CoV-2 將繼續存在，並將從大流行演變為地方性環境。我們認為，2022 年全年將在低收入國家發生大流行，但在高收入國家，這一年將是 2 年，在 22 年秋季開展流行病助推活動，為兒童引發流行病，並為其他人助長。

On Slide 42, you can see the revenue drivers that we anticipate will pay out in 2022. We believe there are 3 components that will drive our COVID-19 vaccine revenues for next year.

在幻燈片 42 上，您可以看到我們預計將在 2022 年支付的收入驅動因素。我們相信有 3 個組成部分將推動我們明年的 COVID-19 疫苗收入。

First, signed APAs. We have already signed around $17 billion of advanced purchase agreements or APAs for delivery in 2022.

首先，簽署APA。我們已經簽署了約 170 億美元的預購協議或預約定價安排，將於 2022 年交付。

Second, APA options. They are up to $3 billion of APAs that are in options. Some options have been converted in Q3 from options to FIM order.

第二，APA選項。他們有高達 30 億美元的 APA 可供選擇。一些期權已在第三季度從期權轉換為 FIM 訂單。

Third, the fall of '22 commercial market. We also believe that the fall of '22, assuming that BLA is granted for boosters, will drive the commercial booster market of up to $2 billion.

三是'22商業市場的下跌。我們還認為，假設 BLA 被授予助推器，22 年秋季將推動高達 20 億美元的商業助推器市場。

So in total, at this point, we believe that 2022 revenues could be between $17 billion and $22 billion. We, of course, continue to have discussions for 2022 APAs with governments and international organizations, including COVAX, the Pan American Health Organization or PAHO, and the African Union.

所以總的來說，在這一點上，我們認為 2022 年的收入可能在 170 億美元到 220 億美元之間。當然，我們將繼續與政府和國際組織（包括 COVAX、泛美衛生組織或 PAHO 和非洲聯盟）討論 2022 年 APA。

For this pan-respiratory franchise, our goal is to evolve the COVID-19 vaccine primary series into fall of '21 boosters, which is happening as we speak and then fall of '22 boosters and then add to a COVID booster of 2 booster in a single dose and then add to COVID and flu and allergy booster in a single dose.

對於這個泛呼吸專營權，我們的目標是將 COVID-19 疫苗初級系列發展為 '21 加強劑的秋季，這正在我們說話時發生，然後是 '22 加強劑的秋季，然後添加到 2 加強劑的 COVID 加強劑中單劑量，然後以單劑量添加到 COVID 和流感和過敏增強劑中。

Our flu vaccine human data should be out soon. And the team is already preparing the Phase II/III for flu, and RSV is moving fast to Phase II/III.

我們的流感疫苗人體數據應該很快就會出來。該團隊已經在為流感準備 II/III 期，RSV 正在快速進入 II/III 期。

If we you look at the health damage of latent viruses, it is profound. EBV is a major cause of infectious mononucleosis. EBV has been reported to increase risk of multiple sclerosis. EBV is associated with certain cancers and autoimmune diseases and EBV associated with a higher risk of long COVID.

如果我們看看潛伏病毒對健康造成的損害，那是深刻的。 EBV是傳染性單核細胞增多症的主要原因。據報導，EBV 會增加多發性硬化症的風險。 EBV 與某些癌症和自身免疫性疾病相關，而 EBV 與長期 COVID 的高風險相關。

CMV associated will be the leading cause of birth defects. CMV is a major driver of immune dysfunction with aging, CMV associated with cardiovascular diseases, CMV associated with cancer and cognitive impairments.

CMV 相關將是導致出生缺陷的主要原因。 CMV 是與衰老相關的免疫功能障礙、與心血管疾病相關的 CMV、與癌症和認知障礙相關的 CMV 的主要驅動因素。

For now, our focus is CMV, EBV and HIV, but we are developing in a labs vaccine against over latent viruses which short human health. Our goal is to eliminate these viruses.

目前，我們的重點是 CMV、EBV 和 HIV，但我們正在實驗室中開發一種疫苗，以對抗縮短人類健康的潛伏病毒。我們的目標是消滅這些病毒。

As we discussed earlier, several cancer and real genetic programs are in the clinic and will provide clinical results soon.

正如我們之前所討論的，一些癌症和真正的基因計劃正在臨床中，並將很快提供臨床結果。

On November 15, AZ will present Phase II data in patients from the VEGF program at the American Health Association. And we are pleased to announce the new modality inhaled pulmonary therapeutics.

11 月 15 日， AZ 將在美國健康協會展示來自 VEGF 項目的患者的 II 期數據。我們很高興地宣布吸入肺治療的新模式。

Modernizing is our effort to expand the use of our platform to create more innovative drugs to help patients. Our strategy to invest internally under the leadership of Dr. (inaudible) dedicated team and to set up licenses agreements with next-generation in gene editing companies. The Metagenomi partnership is a first step in that direction.

現代化是我們努力擴大我們平台的使用範圍，以創造更多創新藥物來幫助患者。我們的戰略是在博士（聽不清）專業團隊的領導下進行內部投資，並與下一代基因編輯公司建立許可協議。 Metagenomi 合作夥伴關係是朝著這個方向邁出的第一步。

The strategic part of the company is very clear and exciting. We want to stop people getting hospitalized from respiratory infection. We wont stop until this goal is achieved.

公司的戰略部分非常清晰和令人興奮。我們希望阻止人們因呼吸道感染而住院。在實現這一目標之前，我們不會停止。

We want to stop fellow human beings from suffering from these latent viruses. We want to bring to market mRNA therapeutics in oncology, cardiology, rare genetic disease, autoimmune. We want to bring therapeutics using gene-editing enzymes. We believe Moderna could become the most impactful drug company in the world.

我們希望阻止人類同胞感染這些潛伏病毒。我們希望將腫瘤學、心髒病學、罕見遺傳病、自身免疫的 mRNA 療法推向市場。我們希望帶來使用基因編輯酶的治療方法。我們相信 Moderna 可能成為世界上最具影響力的製藥公司。

As we scale, we realized that we needed to go further in setting the right framework for our team to understand what made Moderna. So we work through Q2 and Q3 to articulate our mindset, how we behave and make decisions at Moderna. There is more information on our website, and we'll be happy to spend time with those of you who learn more about them.

隨著規模的擴大，我們意識到我們需要進一步為我們的團隊設置正確的框架，以了解是什麼造就了 Moderna。因此，我們通過 Q2 和 Q3 來闡明我們的心態、我們在 Moderna 的行為方式和決策方式。我們的網站上有更多信息，我們很樂意與了解更多信息的人共度時光。

Let me just summarize them at a high level. At Moderna, we act with urgency. Action today compounds the life saves tomorrow. We pursue options in parallel to make the best choice later. We accept risk as the only path to impact. We're obsessed over learning. We don't have to be the smartest. We have to run the fastest. We pivot fearlessly in the pace of new data. We question convention because proven models don't always fuel the future. We push pass possible. We behave like owners, the solutions we are building go beyond any job description. We act with dynamic range, driving strategy and execution at the same time and at every step of the way.

讓我在高層次上總結一下。在 Moderna，我們採取緊急行動。今天的行動會增加明天的生命拯救。我們同時追求選項，以便以後做出最佳選擇。我們接受風險是影響的唯一途徑。我們沉迷於學習。我們不必成為最聰明的人。我們必須跑得最快。我們無所畏懼地適應新數據的步伐。我們質疑慣例，因為經過驗證的模型並不總是為未來提供動力。可以推通行證。我們表現得像業主一樣，我們正在構建的解決方案超出了任何工作描述。我們在動態範圍、駕駛策略和執行力的同時和每一步都採取行動。

We will move this strategy to encourage collective action. We prioritize our platform over any single product. We digitalize everything possible using the power of digital information to maximize our impact on patients.

我們將推動這一戰略以鼓勵集體行動。我們將我們的平台優先於任何單一產品。我們利用數字信息的力量將一切可能的數字化，以最大限度地提高我們對患者的影響。

We want to be the most impactful drug company in the world, we care deeply about doing it the right way. It means being a great company to work for, as exemplified by our seventh consecutive year ranked as the best company to work for by science. But it also means building a company that is responsible in minimizing our impact on the planet. We are proud to have announced earlier this week that we will work to achieve net 0 carbon emission for operations globally by 2030.

我們想成為世界上最具影響力的製藥公司，我們非常關心以正確的方式去做。這意味著成為一家值得為之工作的偉大公司，我們連續第七年被科學評為最佳工作公司就是例證。但這也意味著建立一家負責將我們對地球的影響降至最低的公司。我們很自豪地在本週早些時候宣布，我們將努力在 2030 年之前實現全球運營的零碳排放。

I want to thank the Moderna team for their commitment to our mission, and their relentless work to build the best Moderna over the next 20 years.

我要感謝 Moderna 團隊對我們使命的承諾，以及他們在未來 20 年中為打造最好的 Moderna 所做的不懈努力。

Before we jump into Q&A, we wanted to share the dates of our annual investor event for 2022. Vaccine Day on March 24; Science Day on May 17; and R&D Day on September 8.

在進入問答環節之前，我們想分享一下我們 2022 年年度投資者活動的日期。3 月 24 日的疫苗日； 5月17日科學日；和 9 月 8 日的研發日。

Operator, we're now happy to take any questions.

接線員，我們現在很樂意回答任何問題。

(Operator Instructions)

（操作員說明）

Our first question comes from the line of Salveen Richter from Goldman Sachs.

我們的第一個問題來自高盛的 Salveen Richter。

For 2022, can you walk through the supply aspects. Are you still guiding to up to 3 billion doses here? And can you also speak to demand dynamics? Is there upside to the guidance that you've commented on today for future signed APAs.

對於 2022 年，您能否介紹一下供應方面。你還在指導多達 30 億劑嗎？你也能談談需求動態嗎？您今天為未來簽署的 APA 評論的指導是否有好處。

And then secondly, how confident are you that you can fix these supply issues and over what time frame?

其次，您對解決這些供應問題有多大信心以及在多長時間內解決問題？

Great, Salveen. So let me take those different questions. Let me start with the short term. Yes, we really believe we can fix those short-term supply issues. As I tried to explain in my remarks, those are what I would qualify as teething problems of scaling up so fast. In Q1, it was all about making enough drug substance, and we are literally not waiting to have enough drug substance to fill vials. And the teams scaled very nicely.

太好了，薩爾文。所以讓我來回答這些不同的問題。讓我從短期開始。是的，我們真的相信我們可以解決這些短期供應問題。正如我試圖在我的評論中解釋的那樣，這些就是我認為快速擴大規模的初期問題。在第一季度，一切都是為了製造足夠的原料藥，我們實際上並沒有等待有足夠的原料藥來填充小瓶。團隊的規模非常好。

In Q2, the challenging we had internally was all about filling vials. And the complexity of Q3 has really moved to the, I would say, the back end of the supply chain, which is releasing product and shipping products.

在第二季度，我們內部面臨的挑戰都是關於灌裝小瓶。第三季度的複雜性已經真正轉移到供應鏈的後端，即發布產品和運輸產品。

And the complexity has been around just a number of markets we have to serve. Beginning of the year, it was mostly shipping to CDC in the U.S. and Europe, and that was it. But then as we increased the number of countries to many dozens by now, the complexity is just increasing and it's even further now that we are serving COVAX, we need to go country by country.

複雜性只存在於我們必須服務的一些市場。今年年初，它主要運往美國和歐洲的 CDC，僅此而已。但是隨著我們現在將國家的數量增加到幾十個，複雜性正在增加，而且現在我們正在為 COVAX 提供服務，我們需要逐個國家地去。

So that's just the type of teething problems that we are experiencing right now. We have increased personnel. We have invested in digital to help the teams. So I already expect this to be resolved like we resolved the drug substance challenges in Q1 and the drug product challenges in Q2.

所以這只是我們現在正在經歷的出牙問題的類型。我們增加了人員。我們已經投資於數字化來幫助團隊。所以我已經預計這會像我們解決第一季度的原料藥挑戰和第二季度的藥品挑戰一樣得到解決。

The 2022 -- in terms of drug substance, yes, we could see make up to 3 billion doses in terms of material. As you know, that number was really depending on the booster dose. And now that we're on the other side of that decision with the 50-microgram dose, we confirmed we could make up to 3 billion doses, if there was a need for it.

2022 年——就藥物而言，是的，就材料而言，我們可以看到多達 30 億劑。如您所知，這個數字實際上取決於加強劑量。現在我們對 50 微克劑量的決定持反對態度，我們確認如果有需要，我們可以製造多達 30 億劑。

The challenge in 2022 is going to really be around product form because as the market moves to an endemic market, you're going to need basically vials to be able to go to less number of dose per vile. Again, in the pandemic setting, as you know, we launched with 10 dose per vial, which we think was really an update in low-income countries, we even add more into vials now.

2022 年的挑戰將真正圍繞產品形式，因為隨著市場向地方性市場轉移，您將需要基本上小瓶才能減少每瓶的劑量。同樣，如您所知，在大流行環境中，我們推出了每瓶 10 劑，我們認為這確實是低收入國家的更新，我們現在甚至在小瓶中添加了更多劑量。

But as we think about the endemic market, and we're trying to serve pandemic and endemic at the same time, we just need to keep adding presentation to be relevant to health care workers and health care systems around the world.

但當我們考慮流行病市場時，我們正試圖同時為流行病和流行病服務，我們只需要不斷添加與世界各地的衛生保健工作者和衛生保健系統相關的演示文稿。

So drug substance will not be an issue. There's, of course, as I described, potential upside to those numbers. We still have quite a number of APAs being discussed with countries around the world. We don't know what will happen in terms of epidemiology. Is there a new variant coming? Is it a variant where the current vaccines is still helpful or we need, as Stephen described, a new booster. There is, of course, a big question mark here that we'll follow in epidemiology literally on a daily basis.

所以原料藥不會成為問題。當然，正如我所描述的，這些數字有潛在的上升空間。我們仍在與世界各國討論相當多的預約定價安排。我們不知道在流行病學方面會發生什麼。有沒有新的變種來了？它是當前疫苗仍然有用的變體，還是我們需要，正如斯蒂芬所描述的那樣，新的助推器。當然，這裡有一個很大的問號，我們將每天從字面上關注流行病學。

And then there's so many for boosting people around the world that have had non-mRNA vaccines. As everybody knows, there is a prime of waning immunity over time. So time is not offering as people see the levels antibody going down. And as we have new variants like Delta or potentially others, but we should not forget that most people around the planet have not had an mRNA vaccine injected in their body to date.

然後有很多可以促進世界各地接種過非 mRNA 疫苗的人。眾所周知，隨著時間的推移，免疫力會逐漸減弱。因此，當人們看到抗體水平下降時，時間並沒有提供。由於我們有新的變種，如 Delta 或其他潛在的變種，但我們不應該忘記，迄今為止，地球上的大多數人還沒有在他們的體內註射過 mRNA 疫苗。

And so we believe there is an important need to boost people with mRNA vaccines. And as Paul showed the real world evidence securing the data from CDC and Switzerland. The more we get data and the more time is helping to see -- we see a net differentiation between products. And this doesn't go unnoticed by governments around the world, who are working really hard to preventing hospitalization and death.

因此，我們認為迫切需要用 mRNA 疫苗來增強人們的活力。正如保羅展示了保護來自 CDC 和瑞士數據的真實世界證據。我們獲得的數據越多，就越有時間幫助我們看到——我們看到了產品之間的淨差異。世界各國政府並沒有忽視這一點，他們正在努力防止住院和死亡。

And so there is upside to that. Again, it's a very unpredictable environment. None of us has worked for pandemic before thankfully. But you will be assured that we will keep scaling up manufacturing, we keep in getting with government so that we can maximize how we can help people and the revenue should follow from that.

所以這是有好處的。同樣，這是一個非常不可預測的環境。謝天謝地，我們之前沒有人為大流行工作過。但是您可以放心，我們將繼續擴大製造規模，我們將繼續與政府保持聯繫，以便我們能夠最大限度地幫助人們，並由此獲得收入。

Your next question is from Matthew Harrison with Morgan Stanley.

您的下一個問題來自摩根士丹利的 Matthew Harrison。

Two for me this morning. So first, can we just spend a moment on myocarditis. And I think the overlying question here is why do you think the regulator is more concerned with your vaccine in younger age groups compared to Pfizer, which has obviously already been approved in younger age groups. And then -- and related to that, how much of an impact is this having on uptake and distribution of your vaccine given that we see Pfizer continue to highlight potential differences and bringing that to government's attention.

今天早上給我兩個。所以首先，我們能不能花點時間討論一下心肌炎。而且我認為這裡最重要的問題是，與輝瑞相比，為什麼你認為監管機構更關心你在年輕群體中的疫苗，輝瑞顯然已經在年輕群體中獲得批准。然後 - 與此相關的是，鑑於我們看到輝瑞公司繼續強調潛在差異並將其提請政府注意，這對您的疫苗的吸收和分發有多大影響。

And then secondly, on flu, can you just comment on how you're going to interpret these results? Obviously, we're just going to get titer results. But I think it's your premise that you can achieve a much higher efficacy flu vaccine compared to traditional flu vaccines. So do you think there is a clear correlation in titers to efficacy? And what level of titers would demonstrate very high efficacy?

其次，關於流感，你能評論一下你將如何解釋這些結果嗎？顯然，我們只是要得到滴度結果。但我認為，與傳統流感疫苗相比，您可以獲得更高功效的流感疫苗，這是您的前提。那麼你認為效價與療效有明顯的相關性嗎？什麼水平的滴度會顯示出非常高的功效？

Thank you, Matthew. So this is Stephen. I'll take -- try and take those questions.

謝謝你，馬修。這就是斯蒂芬。我會接受——試著回答這些問題。

So first, look, I think it's most important to say that what we communicated and desired to be maximally transparent last week was that the FDA, unlike other regulators, has asked for some more time to review emerging recent data. And that might take until January.

所以首先，看，我認為最重要的一點是，我們上周傳達並希望最大程度地透明化的是，與其他監管機構不同，FDA 要求更多時間來審查最近出現的數據。這可能要等到一月份。

I think your question is how is that different vis-a-vis what happened with the Pfizer vaccine. I think the most important thing to recognize is that the Pfizer adolescent vaccine was authorized prior to any substantial discussion about myocarditis as a benefit or as a risk. In fact, the signal emerged a few weeks later just before we made our filing. And I think a prudent approach there was to -- the Vertex conducted, there was ongoing discussions.

我認為您的問題是與輝瑞疫苗發生的情況有何不同。我認為最重要的是要認識到輝瑞青少年疫苗是在任何關於心肌炎作為益處或風險的實質性討論之前獲得授權的。事實上，在我們提交申請前幾週，這個信號就出現了。我認為這是一種謹慎的方法—— Vertex 進行了討論，正在進行討論。

But what we've continued to see over the course of -- over the last 4 or 5 months is that for both mRNA vaccines, there's a question of whether there's an increased rate of myocarditis above background in 18 to 24-year-old males, a relatively small population, but an important ones.

但我們在過去 4 或 5 個月的過程中繼續看到的是，對於兩種 mRNA 疫苗，18 至 24 歲男性的心肌炎發病率是否高於背景是一個問題，一個相對較小的人口，但一個重要的。

And I think it's -- in the face of those continuing emerging questions, that the FDA is being diligent and appropriately conservative in their approach and making sure they have the time to review those. And they have continued to come out over time.

而且我認為，面對這些不斷出現的問題，FDA 在他們的方法中正在努力和適當地保守，並確保他們有時間審查這些問題。隨著時間的推移，它們不斷出現。

And so I think, principally, what we're seeing here is -- the difference is a function of timing, which is that the other vaccine had been authorized prior to this concern, and there has been continued emerging data around that.

所以我認為，主要是，我們在這裡看到的是 - 差異是時間的函數，即另一種疫苗在這種擔憂之前已經獲得授權，並且圍繞這一點不斷出現新的數據。

We are very grateful to the FDA for that diligence. I would note that the same information are available to other regulators. And as I have said before, we are authorized for that population internationally. And fortunately, as Paul characterized, we have not seen an increased rate of myocarditis in 12 to 17 years. And we think, over time, the substantial benefits of our vaccine will ultimately win out here. And so we look forward to continuing to work with the FDA. So that's my best version of what I think we heard from them last week.

我們非常感謝 FDA 的努力。我會注意到，其他監管機構也可以獲得相同的信息。正如我之前所說，我們在國際上獲得了針對該人群的授權。幸運的是，正如保羅所描述的，我們在 12 到 17 年內沒有看到心肌炎發病率增加。我們認為，隨著時間的推移，我們的疫苗帶來的巨大好處最終將在這裡勝出。因此，我們期待繼續與 FDA 合作。所以這是我認為我們上週從他們那裡聽到的最好的版本。

The question about how we see that evolving over time. Obviously, internationally, we are participating in the market. In the United States, adolescent vaccinations have substantially tailed off, as we all would note. And so the extent that there is an ongoing need in the United States for vaccination, it is a diminishing market for sure. And again, this is a primary series vaccine. And so we do hope that most people in the world will 0 convert and not need a primary series moving forward.

關於我們如何看待隨著時間的推移而演變的問題。顯然，在國際上，我們正在參與市場。正如我們都注意到的那樣，在美國，青少年疫苗接種已大幅減少。因此，就美國對疫苗接種的持續需求而言，這無疑是一個正在萎縮的市場。同樣，這是一種初級系列疫苗。因此，我們確實希望世界上大多數人都將 0 轉換，並且不需要一個主要的系列向前推進。

The question then of what is that endemic market going forward that is the greatest import. And I tried to summarize that in our view of the evolution of this virus and what that need will be. It is, we believe, in the future, a booster market. And to booster market, targeted at those populations that are higher risk of respiratory disease. Those populations tend to be older adults and immune compromised. Places where we think mRNA-1273 is demonstrating really remarkable efficacy differentiated perhaps. But public data -- publicly-reported data is really encouraging on that dimension.

接下來的問題是，最大的進口是什麼地方性市場。我試圖根據我們對這種病毒的演變以及這種需求的看法來總結這一點。我們相信，在未來，這是一個助推器市場。並促進市場，針對那些呼吸道疾病風險較高的人群。這些人群往往是老年人並且免疫受損。我們認為 mRNA-1273 表現出真正顯著功效的地方可能有所不同。但是公共數據——公開報告的數據在這個方面確實令人鼓舞。

And I would note that it's not a population that's associated to date with any of the vaccines that have an increased rate of myocarditis.

我要指出的是，迄今為止，與心肌炎發病率增加的任何疫苗無關的人群。

And so the benefit risk there, we think, even swings more favorably to 1273, but we'll allow data to continue to develop and ultimately drive this behavior.

因此，我們認為那裡的收益風險甚至會更有利地擺動至 1273，但我們將允許數據繼續發展並最終推動這種行為。

So we are quite encouraged by the performance of the vaccine in the population that we think is going to be most important in the years ahead.

因此，我們對疫苗在我們認為未來幾年最重要的人群中的表現感到非常鼓舞。

The last question was on flu, which is what do we think about that data? Obviously, as you pointed to, there are correlates of protection that have been used previously with HAI titers in influenza vaccine. We will be looking at that as I'm sure everybody will as well as other responses in the immune system as we continue to try and identify the optimal dose. I'm not going to put out there a view of what I think our view of success will look like. I would just say that we have very high expectations for our platform.

最後一個問題是關於流感的，我們如何看待這些數據？顯然，正如您所指出的，以前曾在流感疫苗中使用過與 HAI 滴度相關的保護。我們將對此進行研究，因為我相信每個人都會以及免疫系統中的其他反應，因為我們將繼續嘗試確定最佳劑量。我不會提出我認為我們的成功觀會是什麼樣子的觀點。我只想說我們對我們的平台有很高的期望。

Now we do believe that our performance in older adults, including with the COVID vaccine, but also more recently with the RSV booster study in Phase I demonstrates that our platform does incredibly well in those at highest risk of these respiratory viral diseases. And so we're optimistic that we will continue to show strong performance, hopefully, strongest performance in those populations. But I won't give you a specific titer or number today.

現在我們確實相信，我們在老年人中的表現，包括 COVID 疫苗，以及最近在第一階段的 RSV 加強研究表明，我們的平台在這些呼吸道病毒疾病風險最高的人群中表現得非常好。因此，我們樂觀地認為，我們將繼續表現出強勁的表現，希望在這些人群中表現出最強勁的表現。但我今天不會給你一個具體的滴度或數字。

Yes. And maybe just to add to Stephen's point, Matthew, I think we should not forget the company's strategy, which is a long combination. We believe that combining flu and COVID booster in a single dose and then adding allergy is the critical central part of our strategy. We think it has tremendous value for compliance, for protection. It has a tremendous value in terms of convenience to the consumers. I don't believe that most people will want the flu shot and the COVID shot and allergy shot every fall. And as we heard from the payer and health care worker, that's the value of a product. So we believe the combination is really a critical success factor.

是的。也許只是為了補充斯蒂芬的觀點，馬修，我認為我們不應該忘記公司的戰略，這是一個長期的組合。我們認為，將流感和 COVID 加強劑組合在單劑量中，然後添加過敏是我們戰略的關鍵核心部分。我們認為它對於合規和保護具有巨大價值。它在方便消費者方面具有巨大的價值。我不相信大多數人每年秋天都需要流感疫苗、COVID 疫苗和過敏疫苗。正如我們從付款人和醫療保健工作者那裡聽到的那樣，這就是產品的價值。所以我們相信這種組合確實是一個關鍵的成功因素。

Next question is from Ted Tenthoff with Piper Sandler.

下一個問題來自 Ted Tenthoff 和 Piper Sandler。

Congratulations on all the progress. My question has to do with the emerging Orphan disease pipeline. And I've been really impressed by the progress that you guys are making there in these important patients. And I think the mRNA technology just suits ideally here. So what do you see as sort of the plans over the next couple of years. Kind of take us forward a little bit. What could this pipeline look like? And maybe you can just give us a sense of where you think Moderna will be in the Orphan disease setting in a couple of years.

祝賀所有的進展。我的問題與新興的孤兒病管道有關。你們在這些重要患者身上取得的進展給我留下了深刻的印象。我認為 mRNA 技術非常適合這裡。那麼你認為未來幾年的計劃是什麼。有點帶我們前進一點。這條管道會是什麼樣子？也許您可以讓我們了解一下您認為 Moderna 將在幾年後在孤兒病環境中的位置。

I'll take that too. So first, I think we're very excited about the programs that are already in the clinical space, either already dosing patients or about to start. And so I think the most important thing is looking forward to next year, the demonstration, we would hope, of proof of concept in that rare disease modality.

我也會接受的。所以首先，我認為我們對已經在臨床領域的項目感到非常興奮，這些項目要么已經給患者服用，要么即將開始。所以我認為最重要的是期待明年，我們希望展示這種罕見疾病模式的概念證明。

As you know, we are dosing quite a large number of folks in propionic acidemia, and we've been dosing in methylmalonic acidemia with the opening of the ; GSD1a IND, we'd hope to be following a short order there.

如您所知，我們正在為相當多的人服用丙酸血症，而且我們一直在服用甲基丙二酸血症的藥物； GSD1a IND，我們希望能在那兒得到一個短期訂單。

So all 3 of those are potentials for us to demonstrate the real proof that this technology can be used to correct in more errors of metabolism in these populations. I'll also note that there's a quite a wide range of disease going down as young as 2 years of age in some of the organic acidemias and not the older adults in some of the GSD1a program. So we're going to be demonstrating quite a lot there.

因此，所有這 3 項都是我們有可能證明這項技術可用於糾正這些人群中更多新陳代謝錯誤的真實證據。我還要注意到，在一些有機酸血症中，有相當廣泛的疾病會在 2 歲時下降，而在一些 GSD1a 計劃中則不會出現在老年人中。所以我們將在那裡展示很多東西。

Crigler Najjar presents another opportunity for that proof-of-concept as well as the PKU program when that moves forward, but those are still in preclinical, as I said.

Crigler Najjar 為該概念驗證以及 PKU 計劃提供了另一個機會，但正如我所說，這些仍處於臨床前階段。

So the question is what do we do on the back of that proof-of-concept from any one or all of those programs. What you've seen us do in respiratory vaccines and in vaccines generally is probably the best predictor of how we will respond, which is, as you know, there are a very, very large number of metabolic diseases that could be addressed to deliver through mRNA therapy. We have -- we could list off large groups, but (inaudible) disorders, other organic acidemias, so many beyond that. And even in moving into more broadly present metabolic diseases. So what we would do is we would define that systemic intracellular therapeutic modality as a core modality, just like we did with vaccines a couple of years ago. And that would cause us to dramatically expand that pipeline.

所以問題是我們在任何一個或所有這些程序的概念驗證的基礎上做什麼。你所看到的我們在呼吸道疫苗和疫苗中所做的事情可能是我們將如何應對的最佳預測指標，正如你所知，有非常非常多的代謝疾病可以通過傳遞來解決mRNA治療。我們有——我們可以列出一大群人，但（聽不清）疾病、其他有機酸血症，還有很多。甚至進入更廣泛存在的代謝疾病。所以我們要做的就是將系統性細胞內治療模式定義為核心模式，就像我們幾年前對疫苗所做的那樣。這將導致我們大幅擴展該管道。

Now I can assure you we're looking at those programs in research right now, but we will -- we have held back on moving them into preclinical development and putting them on our pipeline until we've seen the modalities perform.

現在我可以向你保證，我們現在正在研究這些項目，但我們會——我們一直在阻止將它們轉移到臨床前開發中，並將它們放在我們的管道上，直到我們看到這些模式的表現。

So that is probably the most important thing for me, looking at the rare and orphan disease space over the course of the coming year is when do we cross that threshold? And then ultimately, when do we expand dramatically that pipeline of programs.

所以這對我來說可能是最重要的事情，看看未來一年的罕見病和孤兒病領域，我們什麼時候才能跨越這個門檻？然後最終，我們什麼時候才能顯著擴展該程序管道。

That makes a lot of sense, and I really appreciate seeing the new pulmonary disease areas.

這很有意義，我真的很高興看到新的肺部疾病領域。

We have a question from Michael Yee from Jefferies.

我們有一個來自 Jefferies 的 Michael Yee 的問題。

Two questions. One is just trying to clarify guidance. I think there's some confusion around guidance. So I would love to understand some clarification. You lowered 2021 a little bit, I think, by $5 billion, but raised 2022, 2022 by $5 billion. Is that a timing shift of deliveries? And how much of that is just option contracts as you think about 2022 because you've talked about APAs as firm commitments. I'm just trying to understand how much our commitments versus acceptances and how to think about those 2.

兩個問題。一是試圖澄清指導。我認為指導存在一些混亂。所以我很想了解一些澄清。我認為你將 2021 年稍微降低了 50 億美元，但將 2022 年和 2022 年提高了 50 億美元。這是交貨的時間轉移嗎？當您想到 2022 年時，其中有多少只是期權合同，因為您已經將 APA 視為堅定的承諾。我只是想了解我們的承諾與接受有多少，以及如何考慮這兩個。

And then on flu -- following up on the flu question, I think people are looking at labels and looking at fold increases and seroconversion rates of 4 to 7x and 50% to 60% seroconversion rates. Are those accurate numbers? Are those numbers we should be looking at and comparing to? Maybe you could just help us qualify that because I think that's what people are trying to do.

然後是流感 - 跟進流感問題，我認為人們正在查看標籤並查看倍數增加和 4 到 7 倍的血清轉化率和 50% 到 60% 的血清轉化率。這些是準確的數字嗎？這些數字是我們應該關注和比較的嗎？也許你可以幫助我們證明這一點，因為我認為這就是人們正在嘗試做的事情。

So it's Stephane. I'll take the first one and give it through to Stephen. So I think you already highlighted some of the other drivers.

所以是斯蒂芬。我會拿第一個傳給斯蒂芬。所以我認為你已經強調了其他一些驅動因素。

So on '21, so there's 2 things I think that is driving, first is, of course the lower volume. And the second one is price. As you know, we are working very hard with several governments to send products that they have bought for high-income countries like the U.S. to low-income country this side of Christmas.

所以在 21 年，我認為有兩件事在推動，首先當然是較低的音量。第二個是價格。如您所知，我們正在與多個政府合作，將他們為美國等高收入國家購買的產品在聖誕節這一天送到低收入國家。

And so when you think about just the U.S., the U.S., we see that publicly. When we announced our African Union partnership, the U.S. decided to delay to Q2, the delivery over December quarter. That volume is going to African Union at a low tier price. So do you have an impact on the turnover just by doing the math of a lower price on the same volume right there.

所以當你想到美國，美國，我們公開地看到了這一點。當我們宣布與非洲聯盟建立夥伴關係時，美國決定推遲到第二季度，即 12 月季度的交付時間。該數量將以較低的價格流向非洲聯盟。那麼，僅僅通過在相同數量的情況下計算較低的價格，您是否會對營業額產生影響。

And some orders that are moving from December to January on the supply volume side of things. So when you're on to 22, where you have the increase of volume moved from December to January. That is one. We've signed new APAs since the last numbers. And as I said, some options have been exercised. One of them was a COVAX option. That was exercised at the end of Q3. That is now counted as a full APA because of the firm commitment and some prepayments and so on. And so those are the dynamics that are happening.

還有一些訂單在供應量方面從 12 月轉移到 1 月。因此，當您達到 22 歲時，您的交易量增加量從 12 月移至 1 月。那是一個。自上次數字以來，我們已經簽署了新的 APA。正如我所說，已經行使了一些選擇權。其中之一是 COVAX 選項。這是在第三季度末行使的。由於堅定的承諾和一些預付款等，現在算作完整的 APA。這就是正在發生的動態。

The team also is starting to spend a lot of time to commercial team on focusing on the fall of '22 because we think that's going to be an important moment. The mix and match, we think, is critical. That is now allowed in most places. In some countries, that isn't just mix and match for a long time. But the U.S. market, of course, is important, is allowing mix and match.

團隊也開始在商業團隊上花費大量時間專注於 22 年秋季，因為我們認為那將是一個重要的時刻。我們認為，混搭至關重要。現在大多數地方都允許這樣做。在一些國家，這不僅僅是長期以來的混搭。但美國市場當然很重要，它允許混搭。

And as Paul just shared, we believe that as time will go, the data will show that what we believe is that we have a longer duration efficacy vaccine on the market.

正如保羅剛剛分享的那樣，我們相信隨著時間的推移，數據將表明我們相信我們在市場上有一種持續時間更長的有效疫苗。

And today, if you look at data and market research, very few consumer in the U.S. know that. People that are listening to this call know that because you read papers in on a daily basis, a few people in the U.S. We believe there is an opportunity for us between now and let's say next summer to make sure that people understand the facts, understand the real-world evidence so that they can make an informed decision and that includes the health care workers, the pharmacies, the doctors, the nurses that include the consumers directly.

而今天，如果你看一下數據和市場研究，美國很少有消費者知道這一點。聽這個電話的人都知道，因為你每天都在閱讀報紙，美國的一些人我們相信從現在到明年夏天，我們有機會確保人們了解事實，理解真實世界的證據，以便他們可以做出明智的決定，其中包括直接包括消費者在內的衛生保健工作者、藥房、醫生和護士。

And so this is why, as we're starting to sharpen our pencils and probably spend a lot of time working towards the fall of '22, we believe that's another -- that was not if you go back to our previous numbers. We only disclose APAs and options of APAs, the commercial opportunities for a '22, we think is going to be an important vector to the '22 sales. Stephen, answer?

所以這就是為什麼，當我們開始磨鉛筆並且可能花費大量時間在 22 年秋天工作時，我們認為這是另一個原因——如果你回到我們之前的數字，那就不是了。我們只披露 APA 和 APA 的選項，'22 的商業機會，我們認為將成為 '22 銷售的重要載體。斯蒂芬，回答？

Sure. So I'll try and clarify that answer on conversion rates. So we -- it is a Phase I study. And so we are looking at a range of doses, and I have not got access to the data. So just I don't want to presuppose the specific answer yet. As soon as we have the data, we will provide our thorough interpretation of it.

當然。因此，我將嘗試澄清有關轉換率的答案。所以我們——這是一項第一階段的研究。因此，我們正在研究一系列劑量，但我無法獲得數據。所以只是我不想預先假設具體的答案。一旦我們有數據，我們將提供我們對它的徹底解釋。

However, as you point out, generally seroconversion is defined as a fourfold rise in titers above baseline, and we've done that in some of our other studies. And we will be looking at that from the percentage of people who achieve that seroconversion.

然而，正如你所指出的，通常血清轉換被定義為比基線高四倍的滴度，我們在其他一些研究中已經這樣做了。我們將從實現該血清轉化的人的百分比來看待這一點。

And most important to me, we'll be looking at the consistency of that percentage across ages. In particular, the older adults where you often don't achieve the type of the same level of immunogenicity, but we believe with our platform well. There are other endpoints as well in terms of seroprotection defined as absolute titers, again greater than 40 is accepted. We will look how high that goes because that can also be reassuring. But I don't think right now we're ready to guide on a specific target that we will declare success other than looking again at that fourfold rise for measuring seroconversion across the range of agents that we'll be studying in the study.

對我來說最重要的是，我們將研究這個百分比在各個年齡段的一致性。尤其是年長的成年人，你經常沒有達到相同水平的免疫原性，但我們相信我們的平台很好。在定義為絕對滴度的血清保護方面還有其他終點，再次接受大於 40。我們將看看它有多高，因為這也可以讓人放心。但我認為現在我們還沒有準備好指導一個我們將宣布成功的特定目標，而是再次審視我們將在研究中研究的各種藥物的血清轉化率的四倍增長。

Next question is from Gena Wang from Barclays.

下一個問題來自巴克萊銀行的 Gena Wang。

I have 2 regarding the COVID vaccine. And the first question is that given the supply restraints, do you see 100-microgram doses being used as 250-microgram doses.

關於 COVID 疫苗，我有 2 個。第一個問題是，鑑於供應限制，您是否認為 100 微克劑量被用作 250 微克劑量。

And then also any hesitance due to safety concerns, and we did see a few countries put a cautionary action on Moderna vaccine.

然後還有出於安全考慮的任何猶豫，我們確實看到一些國家對 Moderna 疫苗採取了謹慎行動。

And my second question is, in the U.S., if we do the math, you completed delivery of 300 million doses and then U.S. exercised total doses of 410 million for 2021 and the 90 million doses in first quarter 2022. So just wondering how much of the remaining 110 million doses in 4Q '21 will flow through next year.

我的第二個問題是，在美國，如果我們算一下，你們完成了 3 億劑的交付，然後美國在 2021 年行使了 4.1 億劑的總劑量，在 2022 年第一季度行使了 9000 萬劑。所以只是想知道有多少21 年第 4 季度剩餘的 1.1 億劑疫苗將在明年投放。

So I can try and take the first question, although invite Paul as well. So I think in terms of -- you referenced some of the more recent communications that happened from public health officials, for instance, in the Nordics and elsewhere, I would note that those same communications literally often the same documents and include reference to the fact that there's very strong efficacy for the Moderna COVID-19 vaccine.

所以我可以嘗試回答第一個問題，儘管也邀請 Paul。所以我認為 - 你提到了公共衛生官員最近發生的一些通信，例如，在北歐和其他地方，我會注意到這些相同的通信實際上通常是相同的文件，並且包括對事實的引用Moderna COVID-19 疫苗的功效非常強大。

And in fact, some of those Nordic country communications include reference to the fact that it looks to be potentially greater in terms of protection as emphasis for why the vaccine not only is still recommended in many of those jurisdictions, but ultimately, provide very favorable benefit risk.

事實上，一些北歐國家的通訊包括提到它在保護方面看起來可能更大的事實，作為強調為什麼疫苗不僅在許多這些司法管轄區仍然被推薦，而且最終會提供非常有利的好處風險。

And so we continue to believe that whole picture looking at the benefit and quantifying that benefit, which we think is substantial and larger than any risks contemplated here is really important. And we, again, look to those communications that clearly state that. Paul, anything you would add to that?

因此，我們繼續相信，從整體上審視收益並量化收益，我們認為這比這裡設想的任何風險都重要且更大。我們再次關注那些明確說明這一點的通信。保羅，你有什麼要補充的嗎？

Only, Stephen, that recently, I think last week, the WHO gave updated guidance, continuing to endorse the vaccines in mRNA-1273. And I think as they are doing their analysis of these data sets -- subsets that they need to think about potential biases that occur in general practice, looking at the primary vaccination schedule, the difference in timing. We know that vaccines are used differently sometimes, and that may account for these. But I think clear standing behind the data. Stephen?

只是，斯蒂芬，最近，我認為上週，世界衛生組織給出了更新的指導，繼續支持 mRNA-1273 中的疫苗。我認為，當他們對這些數據集進行分析時——他們需要考慮一般實踐中發生的潛在偏差的子集，查看主要疫苗接種計劃，時間差異。我們知道疫苗有時會以不同的方式使用，這可能是這些原因的原因。但我認為清楚地站在數據背後。斯蒂芬?

Yes. I mean just as a closing comment, I would just reference, we have entered in some of these markets into a very interesting phase of the pandemic, which is that we are in the lower risk population and we are providing vaccination to them as appropriate. But -- so as we do that, we're looking at benefit risk in the most -- increasingly cautious ways, and that's appropriate. But as we look forward to next year and we start thinking about boosting and particularly, the seasonal market are protecting those at our highest risk, I think that calculus obviously changes pretty dramatically.

是的。我的意思是作為最後的評論，我只想提一下，我們已經在其中一些市場進入了大流行的一個非常有趣的階段，即我們處於風險較低的人群中，我們正在適當地為他們提供疫苗接種。但是 - 所以當我們這樣做時，我們正在以最謹慎的方式看待收益風險，這是適當的。但是當我們期待明年並且我們開始考慮提振，特別是季節性市場正在保護那些處於我們最高風險的人時，我認為微積分顯然發生了相當大的變化。

And so I think we are in a period of time where we are, again, looking at the lowest risk populations. And I think that is transient period time ultimately because it is high risk populations that are of greatest concern looking forward from 2022.

所以我認為我們正處於一個我們再次關注風險最低的人群的時期。我認為這最終是短暫的時期，因為從 2022 年開始，最令人擔憂的是高風險人群。

Yes. Maybe just to add just a bit of color. I've had a chance to speak with a couple of health ministers across the world in the last week or 2. And I think people are very clear that the risk is low. That it's very manageable, as Paul said, and it's only in the male 18 to 24.

是的。也許只是為了添加一點顏色。在過去一周或兩週內，我有機會與世界各地的幾位衛生部長交談。我認為人們非常清楚風險很低。正如保羅所說，這很容易控制，而且只發生在 18 到 24 歲的男性身上。

And those health ministers were they care about going back to the risk profile that Stephen just mentioned, take care of about having the winter where they don't have hospitals exploding again. And this is driven by the 50 and above, the 40 and above, where they know the vaccine, as Paul mentioned, with the data from the U.S. or Switzerland or many other countries that 1273 vaccine seems to be a vaccine providing the longest protection of efficacy, and that's what they care about.

那些衛生部長是他們關心回到斯蒂芬剛才提到的風險狀況，關心他們沒有醫院再次爆炸的冬天。這是由 50 歲及以上、40 歲及以上的人推動的，正如保羅所說，他們知道疫苗，來自美國或瑞士或許多其他國家的數據表明，1273 疫苗似乎是一種提供最長保護時間的疫苗功效，這就是他們所關心的。

And so I think that people are getting educated and looking at the data. They're just trying to look at the facts and figure out in a very practical way, how they keep the economies running, how they keep people out of our hospitals and very focused on the high population.

所以我認為人們正在接受教育並查看數據。他們只是試圖查看事實並以非常實際的方式弄清楚，他們如何保持經濟運行，如何讓人們遠離我們的醫院，並且非常關注高人口。

As in many countries, the boosters are not approved in the younger population, whereas they are being really advertised and promoted in the older population so that people get boosted and don't get sick and hospitalized this winter.

與許多國家一樣，助推器並未在年輕人群中獲得批准，而在老年人群中卻得到了真正的宣傳和推廣，以便人們在今年冬天得到助推器並且不會生病和住院。

On the U.S. government, Gena, we don't comment on volume. U.S. government is a private contract to the government. But indeed, there are some shift from Q4 to next year, both Q1 and Q2.

對於美國政府，Gena，我們不對數量發表評論。美國政府是政府的私人合同。但實際上，從第四季度到明年，第一季度和第二季度都有一些轉變。

Next question is from Cory Kasimov with JPMorgan.

下一個問題來自摩根大通的 Cory Kasimov。

Two for me as well. So first of all, in terms of the 2022 APAs that you outlined, are the $17 billion worth of existing contracts constructed as firm commitments or do countries have -- the contracts have optionality embedded in them where in countries don't necessarily have to take the full amount depending on the evolution of the pandemic.

兩個對我來說也是如此。因此，首先，就您概述的 2022 年預約定價安排而言，價值 170 億美元的現有合同是作為堅定承諾構建的，還是國家有——這些合同具有嵌入其中的選擇性，而國家不一定必須採取全部金額取決於大流行的演變。

And then my second question is, given your comments on the call about potentially moving into the endemic phase by the second half of next year. Should we think about 2022 revenue as being weighted towards the first half of the year?

然後我的第二個問題是，鑑於您對關於可能在明年下半年進入流行階段的呼籲的評論。我們是否應該將 2022 年的收入視為對上半年的加權？

Thank you, Cory. So let me take this part. The APAs do not have options. When we say 17 billion of APAs, those are firm orders -- signed orders and all our APAs have upfront payments. David did a nice job walking you through the cash upfront we are receiving for those contracts. It's one of the way that we are conducting our business. We want people to be very committed and to have a material upfront of the total value of the deal when they signed.

謝謝你，科里。所以讓我來做這部分。 APA 沒有選項。當我們說 170 億個 APA 時，這些都是確定的訂單——簽署的訂單，我們所有的 APA 都有預付款。大衛做得很好，帶您了解我們為這些合同收到的預付款。這是我們開展業務的方式之一。我們希望人們非常投入，並在簽署時對交易的總價值做出重大貢獻。

The options components that we characterize is up to 3 billion as of today. Those are true options, meaning people are reserving capacity. And sometimes it's for financing rhythm because, again, as I said, we do not do APAs without upfront.

截至今天，我們描述的期權組件已達 30 億個。這些是真正的選擇，這意味著人們正在保留容量。有時是為了融資節奏，因為，正如我所說，我們不會在沒有預付款的情況下進行 APA。

And one of the best examples today probably is COVAX. We had to do a quarterly option with COVAX. As I said, it just exercised our Q2 option at the end of Q3. But Q3 2022 and Q4 2022 COVAX still options and it's mostly because of the funding issue. They don't have the cash. They get cash from their different funders, which are mostly government and foundation on the kind of a month-to-month basis. And so we did that to help COVAX and to do the right thing to help the planet. As you know, we don't have to do options. We say, if you want the vaccine when you sign a contract and you pay an upfront. But with COVAX, we have to do so. We thought it was the right thing to do. And so we expect, if they want their Q3 volume, that in Q1, they will exercise the options -- sorry end of Q4, they will exercise the options.

今天最好的例子之一可能是 COVAX。我們必須使用 COVAX 進行季度選擇。正如我所說，它剛剛在第三季度末行使了我們的第二季度期權。但是 2022 年第三季度和 2022 年第四季度的 COVAX 仍然可以選擇，這主要是因為資金問題。他們沒有現金。他們從不同的資助者那裡獲得現金，這些資助者主要是政府和基金會，按月計算。所以我們這樣做是為了幫助 COVAX 並做正確的事情來幫助地球。如您所知，我們不必做選擇。我們說，如果您在簽訂合同並預付了費用時想要接種疫苗。但是對於 COVAX，我們必須這樣做。我們認為這是正確的做法。因此，我們預計，如果他們想要第三季度的交易量，他們將在第一季度行使期權——抱歉，第四季度末，他們將行使期權。

On the endemic and the ventilation of the sales over the year, I think it will be dangerous to assume at this stage one way or other in terms of first half and second half because of volume and also pricing.

關於全年銷售的流行和通風，我認為在這個階段，由於數量和定價的原因，在上半年和下半年以某種方式假設是危險的。

As you get a sense, the COVAX, the African Union and some BARDA deals we have are lower prices and David mentioned that, fewer pricing. And so there might be a large volume, but probably way lower than what the commercial market could drive, which we believe is going to be above what has been the pandemic price again because of volume. And so we are so people stocking ahead of when they need to inject in pharmacies. I would be cautioned that assuming Q1 to be lower and Q2 is a bit too early.

正如您所了解的，我們擁有的 COVAX、非洲聯盟和一些 BARDA 交易價格較低，大衛提到，價格較低。因此可能會有很大的成交量，但可能遠低於商業市場的驅動力，我們認為由於成交量，這將再次高於大流行的價格。因此，當人們需要在藥店注射時，我們會提前備貨。我會提醒我，假設 Q1 較低而 Q2 有點為時過早。

Next question is from Geoff Meacham from Bank of America.

下一個問題來自美國銀行的 Geoff Meacham。

I just had one more on the flu program, maybe for Stephen. It's highlighted that you'll see an increase in antibody titers. I was just thinking for the combo study though with 1273, what other factors do you need to address to derisk that study? And just I guess I'm trying to determine how to optimize the regimen by things like dose titration or even selecting the population by more urgent need for the COVID booster side of things.

我剛剛在流感項目上又多了一個，也許是給斯蒂芬的。突出顯示您會看到抗體滴度增加。我只是在考慮使用 1273 進行組合研究，您還需要解決哪些其他因素才能取消這項研究？只是我想我正試圖確定如何通過劑量滴定等方法優化治療方案，甚至通過更迫切需要 COVID 助推器方面來選擇人群。

Thank you for the question. It's a great one. So what we're going to be looking at in the combinations are actually the things that you just pointed to. And so in particular, we do believe the most of the value of respiratory vaccination in the near term boosting will be in older adults, 50-plus or 60-plus depending upon how you want to look at it, very similar to the RSV population, certainly for the flu population and recommendations globally. And we think COVID moves that direction as well.

感謝你的提問。這是一個偉大的。所以我們要在組合中看到的實際上是你剛剛指出的東西。因此，特別是，我們確實相信近期加強呼吸道疫苗接種的最大價值將是老年人，50 多歲或 60 多歲，具體取決於您如何看待它，與 RSV 人群非常相似，當然對於全球流感人群和建議。我們認為 COVID 也朝著這個方向發展。

And so as we look to the first part of the question, where do we intend to optimize that ratio in immunogenicity. It really is towards those higher risk populations that do need, we think, a respiratory booster every year. When it comes to looking at the -- what are the combination of things that we're going to be doing in selecting that ratio in dose, obviously, it's mostly going to be immunogenicity and the tolerability profile. Fortunately, these vaccines have been very safe to date in these older adult populations. None of the concerns that we're having about myocarditis really exists in the 50 plus, 60 plus populations.

因此，當我們研究問題的第一部分時，我們打算在哪裡優化免疫原性比率。我們認為，這確實是針對那些每年確實需要呼吸助推器的高危人群。當談到 - 在選擇劑量比例時我們將要做的事情的組合是什麼，顯然，它主要是免疫原性和耐受性概況。幸運的是，迄今為止，這些疫苗在這些老年人群中是非常安全的。我們對心肌炎的擔憂在 50 多個、60 多個人群中都不存在。

And so we feel very confident on the overall safety profile. But the question will be, where are we in optimizing the immunogenicity against endpoints that are pretty well validated now in COVID, and where are we against the immunogenicity against endpoints that are also broadly accepted in influenza.

因此，我們對整體安全狀況充滿信心。但問題是，我們在哪裡優化針對現在在 COVID 中得到很好驗證的終點的免疫原性，以及我們在哪裡反對針對在流感中也被廣泛接受的終點的免疫原性。

We will be doing this for a range of different -- it's a 4-strain, seasonal strain vaccine. And so we want to make sure there's no interference between those and that we're able to achieve strong balance immunity across the 4 flu strains plus the COVID vaccine.

我們將針對一系列不同的疫苗進行此操作——這是一種 4 株季節性株疫苗。因此，我們希望確保它們之間沒有乾擾，並且我們能夠在 4 種流感病毒株和 COVID 疫苗之間實現強大的平衡免疫。

I think we have approximate targets based on the immunogenicity we saw from Phase III and the immunogenicity we're seeing in the booster studies. But the open question is are we going to need all of that for the COVID portion of our vaccine going forward.

我認為根據我們從 III 期看到的免疫原性和我們在加強研究中看到的免疫原性，我們有大致的目標。但懸而未決的問題是，我們未來的疫苗中的 COVID 部分是否需要所有這些。

And so we'll continue to follow over time whether we see more durable protection and therefore, you might be able to optimize further that dose, if there was a reason to do so. And then the second part is with the seasonal annual flu component. We just want to understand, particularly in the older adult population where flu vaccines have had less clear efficacy every season, is maybe the way of say it. And there is an opportunity for improvement by raising those titers. We're going to want to look to whether or not we need to get those titers above what have been achieved by others. And I'll note that there's a precedent even for high-dose flu vaccines in that market that have been differentiated on price and grabbing market share.

因此，隨著時間的推移，我們將繼續關注我們是否看到更持久的保護，因此，如果有理由這樣做，您可能能夠進一步優化該劑量。然後第二部分是季節性的年度流感成分。我們只是想了解，尤其是在流感疫苗每個季節都沒有明顯效果的老年人群中，也許是這樣說的。並且通過提高這些滴度有改進的機會。我們將想看看我們是否需要讓這些滴度高於其他人已經達到的水平。而且我會注意到，即使是高劑量流感疫苗在該市場上也有先例，它們在價格和搶占市場份額方面存在差異。

And so it could cause us to look in that 60-plus or 50-plus population at really indexing more to those flu antigens and making sure that we exceed or at least achieve that similar high degree of seroconversion there.

因此，它可能會導致我們在 60 多或 50 多人口中尋找更多的流感抗原指數，並確保我們超過或至少達到類似的高度血清轉化。

So those are the factors that we'll look at around the 1073 program that we've announced. We're looking at a range of ratios.

因此，這些是我們將圍繞我們宣布的 1073 計劃研究的因素。我們正在研究一系列比率。

Fortunately, we're going to have experience -- we already have experience in flu and COVID from our prior work, and it will be a demonstration we hope, of the ability to combine vaccines.

幸運的是，我們將獲得經驗——我們已經從之前的工作中獲得了流感和 COVID 方面的經驗，我們希望這將證明結合疫苗的能力。

I will note as a final comment, we have done combination respiratory vaccines in the past, including in adults with the 1653 program. And so we do have a basis we're beginning to think about how we might combine those antigens going forward.

作為最後的評論，我將指出，我們過去曾做過聯合呼吸道疫苗，包括在 1653 計劃中用於成人的疫苗。因此，我們確實有一個基礎，我們開始考慮如何將這些抗原結合起來。

But ultimately, we'll let the 1073 study and the early clinical experiences there be confirmatory around this.

但最終，我們將讓 1073 研究和早期臨床經驗圍繞這一點得到證實。

We have a question from Joseph Stringer from Needham.

我們有一個來自 Needham 的 Joseph Stringer 的問題。

Two from me. Just curious on the guidance for -- the $2 billion guidance for the U.S. fall 2022 booster market. Can you help us understand what assumptions are sort of built into that number? Is that based on sort of your internal expectations around relative percentage of individuals that would -- fully vaccinated individuals that would get a booster or just trying to handicap what the variance could be around that.

兩個我。只是對美國 2022 年秋季助推器市場 20 億美元的指導感到好奇。您能幫助我們了解該數字中包含哪些假設嗎？那是基於你對個人相對百分比的內部預期——完全接種疫苗的人會得到助推器，或者只是試圖限制可能出現的差異。

And then for CMV, can you give us a sense for the relative time lines for enrollment of that Phase III trial and when we could see the initial data from that?

然後對於 CMV，您能否告訴我們參與 III 期試驗的相對時間線，以及我們何時可以從中看到初始數據？

So on the fall of '22, so the commercial team has spent quite a lot of time modeling different assumptions in terms of volume of people who want the boost, market share and, of course, pricing. I cannot comment further for competitive reason right now, especially on the pricing piece, but we will do that in due time. But indeed, I mean, it's typical commercial analysis that the team that has done many times before in other companies have run through the last few months.

因此，在 22 年秋天，商業團隊花費了大量時間對想要提升的人數、市場份額，當然還有定價方面的不同假設進行建模。出於競爭原因，我現在無法進一步評論，尤其是在定價方面，但我們會在適當的時候這樣做。但實際上，我的意思是，以前在其他公司做過很多次的團隊在過去幾個月裡一直在運行，這是典型的商業分析。

Great. And on the enrollment of CMV, thank you for the question. So we're -- the answer from our target perspective is as fast as we can because we ultimately think there's just such a huge unmet need here, and we're excited to get the study going. There are some caveats that I should put around that, which is it probably won't be as fast as we did in COVID, which was obviously in a couple of months, because we are targeting a population at high risk of disease. And in this case, we're looking for women of child-bearing age who are exposed to seroconversion of COVID-19 -- with CMV. And that is often those that are exposed to children because that's the primary vector for those infections. And so we want to make sure that we get the right population. And that matters because this is a case-driven study. As we're kind of familiar with based on COVID-19, the number of cases we achieve that will ultimately dictate those interim analyses that we're looking for in the time ahead.

偉大的。關於CMV的註冊，謝謝您的提問。所以我們 - 從我們的目標角度來看答案是盡可能快的，因為我們最終認為這裡有如此巨大的未滿足需求，我們很高興能夠進行研究。我應該提出一些警告，那就是它可能不會像我們在 COVID 中那樣快，這顯然是在幾個月內，因為我們的目標是高患病風險的人群。在這種情況下，我們正在尋找暴露於 COVID-19 血清轉化的育齡婦女 - 帶有 CMV。這通常是那些接觸兒童的人，因為這是這些感染的主要媒介。所以我們要確保我們得到合適的人口。這很重要，因為這是一個案例驅動的研究。正如我們基於 COVID-19 所熟悉的那樣，我們實現的案例數量最終將決定我們在未來一段時間內尋找的那些中期分析。

And so it makes sense to try and enrich for the at-risk population. So you might see a slower enrollment curve or it might go really fast. We're going to work as hard as we can go very fast. But the most important thing is that we need to be enrolling those that are at highest risk because we think that will ultimately generate the cases that accelerates the interim readout. We won't -- because it is an interim readout that's driven on the cases, I can't predict when that will happen. What I can do is I can try and enrich for those cases in the way I just described.

因此，嘗試豐富高危人群是有意義的。所以你可能會看到一個較慢的註冊曲線，或者它可能會非常快。我們將盡可能快地努力工作。但最重要的是，我們需要招募那些風險最高的人，因為我們認為這最終會產生加速中期讀數的案例。我們不會——因為它是由案件驅動的臨時讀數，我無法預測何時會發生這種情況。我能做的是，我可以按照我剛才描述的方式嘗試和豐富這些案例。

Next question is from Emmanuel Papadakis from Deutsche Bank.

下一個問題來自德意志銀行的 Emmanuel Papadakis。

And next is from Mani Foroohar with SVB Leerink.

接下來是來自 Mani Foroohar 的 SVB Leerink。

A couple of quick ones. Can you give us a sense of when we might see, if any, the impact of pricing shift to increase deliveries to low and middle income countries that Stephane mentioned. Is that something that we'd start to see a little bit of early next year? Is that more of a 4Q phenomenon in terms of the budgetary timing and sort of quarterly contract that Stephane talked about.

幾個快速的。您能否讓我們了解一下我們何時可能會看到（如果有的話）定價轉變對增加對斯蒂芬提到的低收入和中等收入國家的交付的影響。這是我們明年年初開始看到的東西嗎？就 Stephane 談到的預算時間和季度合同而言，這更像是 4Q 現象嗎？

Secondarily, I have a few small piggy back question on the numbers. You -- on Slide 15, the $6.7 billion in deposits, that was all for APAs for '21 or '22? Or does some of that applied to APAs for delivery -- for contracts for 2023.

其次，我有一些關於數字的小問題。你——在幻燈片 15 上，67 億美元的存款，都是為了 21 年或 22 年的預約定價安排？或者其中一些適用於 APA 的交付——對於 2023 年的合同。

Thirdly, your CapEx guidance a little lower than it was last Q. Is that $50 million to $150 million that you took out of that is that absolute savings? Or is that just going to get pushed into next year as some of the contract revenues were?

第三，您的資本支出指導比上一個問題略低。您從中取出的 5000 萬到 1.5 億美元是絕對節省嗎？還是會像一些合同收入一樣將其推遲到明年？

And then finally, a little more substantive of the question. How much perspective can you give us on you're able to potentially compete for share on contracting in EU, the competitor Pfizer/BioNTech locked in pretty large contracts on volume for the next 2 years? Is there an opportunity for you guys to start capturing more share returns or relevant to the EU?

最後，更實質性的問題。你能給我們多少看法，你有可能在歐盟競爭合同份額，競爭對手輝瑞/BioNTech 在未來 2 年鎖定了相當大的合同量？你們有沒有機會開始獲得更多的股票回報或與歐盟相關的？

And last and finally, we talked on the last quarter about potentially access to China market where you guys are essentially not existing at this point. And you have mentioned going to via JV, can you give us an update on status of your ability to access that market, discussion of the JV to compete with BionTech/Pfizer? Sorry for the barrage of questions.

最後也是最後，我們在上個季度談到了可能進入中國市場的機會，你們目前基本上不存在。您已經提到通過合資企業，您能否向我們介紹您進入該市場的能力的最新情況，以及與 BionTech/輝瑞公司競爭的合資企業的討論？抱歉一連串的問題。

So I'll take a few and David, if you can take the financials, that would be great.

所以我會拿一些，大衛，如果你能拿財務，那就太好了。

So on Q4, we already actually picked COVAX products. And the African Union will be in December, as we communicated in the press release. And it's going to be a big ramp into next year, obviously. In terms of European share, which was one of your questions. So if you look at it, there's a few things.

所以在第四季度，我們實際上已經選擇了 COVAX 產品。正如我們在新聞稿中所傳達的那樣，非洲聯盟將在 12 月舉行。顯然，這將是明年的一大步。就歐洲份額而言，這是您的問題之一。所以如果你看它，有幾件事。

First, in Europe, if you remember, we had a late and slow launch in Europe because we had no manufacturing capacity in Europe. If you recall, when we have had the pandemic, we had Norwood that we converted, and we were not allowed to export or serve the U.S. market. So Lonza came online a bit later in Norwood because we have (inaudible) some time in the summer to just get machines and get the facility ready.

首先，在歐洲，如果你還記得的話，我們在歐洲推出的時間很晚而且很慢，因為我們在歐洲沒有製造能力。如果你還記得，當我們發生大流行時，我們有諾伍德，我們被轉換了，我們不被允許出口或服務於美國市場。因此，Lonza 稍後在諾伍德上線，因為我們（聽不清）夏天有一些時間來獲取機器並準備好設施。

And so indeed, in Europe, we have a lesser share than we have in the U.S., except for example, for Switzerland like you saw earlier.

因此，事實上，在歐洲，我們的份額比在美國的份額要少，除了你之前看到的瑞士。

And so as the country gets more and more of an understanding first that mRNA vaccines are superior. The other vaccines that other than mRNA, I'm not sure, used anymore as my understanding, they're mostly given through COVAX.

因此，隨著該國越來越多地首先了解 mRNA 疫苗的優越性。我不確定除了 mRNA 以外的其他疫苗，據我了解，它們主要是通過 COVAX 提供的。

I think we have an interesting opportunity because as I shared, as you take -- you talk to health care leaders, health minister, as you get more and more data that Paul shared, we have a better and better understanding that the 2 mRNA vaccines are not the same.

我認為我們有一個有趣的機會，因為正如我分享的那樣，正如你所接受的那樣——你與衛生保健領導人、衛生部長交談，隨著你獲得保羅分享的越來越多的數據，我們對 2 種 mRNA 疫苗的理解越來越好不一樣。

And so again, as we look into 2022, we already have a contract with Europe in '22. And we are discussing also with country by country on the data and using the benefit of the Moderna vaccine versus the other one.

同樣，當我們展望 2022 年時，我們已經在 22 年與歐洲簽訂了合同。我們也在逐個國家討論數據，並使用 Moderna 疫苗與另一種疫苗的優勢。

And then the other question is going to stay in Europe, which is today, contracts are done at the European level because this was organized and agreed by Europe because of the pandemic.

然後另一個問題將留在歐洲，也就是今天，合同是在歐洲層面完成的，因為這是由歐洲組織和同意的，因為大流行。

The big question that's going to be out there is when do countries start to be buying by themselves because they have to make guesses of supply when they set up '21 and '22 agreements that might not meet the needs that they have, as we understand that they have a different profiles of a vaccine.

將會出現的一個大問題是，各國何時開始自行購買，因為據我們了解，當他們制定可能無法滿足其需求的 '21 和 '22 協議時，他們必須猜測供應他們有不同的疫苗概況。

And so I think it's going to be quite interesting to see the share opportunity that we have in Europe. Also as we build our teams, you remember, we had no infrastructure in Europe, 0, not 1 Moderna employee in commercial. We have now teams in several countries in Europe, in the U.K., in Spain, New France, in Germany, building the Italian team as we speak. So I think that also helped because we get feet on the ground to be able to get the message that -- of the real world evidence data. David, do you want to take the capital financial questions.

因此，我認為看到我們在歐洲擁有的分享機會將會非常有趣。同樣，當我們建立我們的團隊時，您還記得，我們在歐洲沒有基礎設施，0 名，而不是 1 名 Moderna 商業員工。我們現在在歐洲的幾個國家、英國、西班牙、新法國和德國都有團隊，在我們說話的時候正在組建意大利團隊。所以我認為這也有幫助，因為我們腳踏實地，能夠獲得關於真實世界證據數據的信息。大衛，你想問資本財務問題嗎？

Yes, sure. So in terms of the deposits, the $6.7 billion we have in hand, I would just say the preponderance of those deposits are for deliveries either in '21 and in '22. There may be some small amounts in '23, but it's pretty early in terms of contracting there.

是的，當然。因此，就存款而言，我們手頭的 67 億美元，我只想說這些存款的優勢是用於 21 年和 22 年的交付。 23 年可能會有一些少量的金額，但就在那裡簽訂合同而言還為時過早。

Secondly, in terms of CapEx, I think the answer is yes, you can expect, as I said, we're going to see a notable increase in our CapEx next year. But generally, in terms of the reduction this year, it's a combination of things moving into the first quarter of next year and also we're running, in some cases, at or below the estimated investment requirements. So it's a combination of those 2.

其次，就資本支出而言，我認為答案是肯定的，正如我所說，您可以預期，明年我們的資本支出將顯著增加。但總的來說，就今年的減少而言，這是進入明年第一季度的綜合因素，而且在某些情況下，我們的運行速度達到或低於估計的投資要求。所以它是這兩個的組合。

Great. And on potential China JV. I know you guys have mentioned it in the last call, I don't know if there's been any progress?

偉大的。以及潛在的中國合資企業。我知道你們在上次通話中提到過，不知道有沒有進展？

Yes. So nothing to announce today, but we [do value for] people in China.

是的。所以今天沒有什麼要宣布的，但我們[為]中國人做有價值的事情。

There are no further questions at this time. I would now like to turn the conference back to Mr. Stephane Bancel.

目前沒有其他問題。我現在想把會議轉回給 Stephane Bancel 先生。

Well, thank you very much for joining us. And if you have any further questions, you know where to reach Lavina and the team. Have a great day. Bye.

好的，非常感謝您加入我們。如果您還有其他問題，您知道在哪裡可以聯繫到 Lavina 和團隊。祝你有美好的一天。再見。

This concludes today's conference call. Thank you for joining. You may now disconnect.

今天的電話會議到此結束。感謝您的加入。您現在可以斷開連接。