莫德納 (MRNA) 2021 Q1 法說會逐字稿

Good morning. My name is Dee Tamara, and I will be your operator today. Welcome to Moderna's First Quarter Earnings Call. (Operator Instructions)

早安.我叫迪伊·塔瑪拉 (Dee Tamara)，今天我將擔任您的接線員。歡迎參加 Moderna 第一季度財報電話會議。 （操作員說明）

Please be advised that the call is being recorded.

請注意，通話正在錄音。

At this time, I'd like to turn the call over to Lavina Talukdar, Head, Investor Relations at Moderna. Please proceed.

現在，我想將電話轉給 Moderna 投資者關係主管 Lavina Talukdar。請繼續。

Thank you, Dee Tamara. Good morning, everyone. Thank you for joining us on today's call to discuss Moderna's First Quarter 2021 Financial Results and Business Updates. You can access the press release 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，迪·塔瑪拉。大家，早安。感謝您參加今天的電話會議，討論 Moderna 2021 年第一季度財務業績和業務更新。您可以訪問我們網站的投資者部分，查看今天早上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; Tal Zaks, our Chief Medical Officer; Corinne Le Goff, our Chief Commercial Officer; and Juan Andres, our Chief Technical and Operations Officer.

參加今天電話會議的是我們的首席執行官 Stephane Bancel； David Meline，我們的首席財務官；斯蒂芬·霍格，我們的總裁； Tal Zaks，我們的首席醫療官； Corinne Le Goff，我們的首席商務官；和我們的首席技術和運營官胡安·安德烈斯。

Before we begin, please note that this conference call will include forward-looking statements made pursuant to the safe harbor provision 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. We undertake no obligation to update or revise the information provided on this call as a result of new information or future results or developments.

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 以及我們向SEC 提交的文件，了解以下重要風險因素：可能導致我們的實際表現和結果與這些前瞻性陳述中明示或暗示的表現和結果存在重大差異。我們不承擔因新信息或未來結果或發展而更新或修改本次電話會議中提供的信息的義務。

On Slide 3, please see the important indication and safety information for our COVID-19 vaccine. which has been authorized 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。它已被授權在美國和世界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斯蒂芬。

Thank you, Lavina. Good morning or good afternoon, everyone. Thank you for taking the time to join our Q1 2021 conference call.

謝謝你，拉維娜。大家早上好或者下午好。感謝您抽出時間參加我們的 2021 年第一季度電話會議。

We'll start by a quick business review of the quarter before Corinne walks you through commercial update. David will then walk you through the key financials. Stephen will provide a clinical update, especially new human data about 2 of our COVID-19 booster candidates, mRNA-1273, the currently authorized vaccine; and mRNA-1273.351, the variant specific booster to B.1.351 first identified in South Africa. I will then come back to close.

在 Corinne 引導您完成商業更新之前，我們將首先快速回顧本季度的業務。然後，大衛將帶您了解關鍵的財務數據。 Stephen 將提供臨床更新，特別是有關我們的 2 種 COVID-19 加強候選疫苗 mRNA-1273（目前已獲授權的疫苗）的新人體數據； mRNA-1273.351，B.1.351 的變體特異性增強劑，首次在南非發現。然後我會回來結束。

The Moderna COVID-19 vaccine is now available and protecting people in 37 countries around the world. And with the WHO authorization last Friday night, the number of countries where our vaccine will be available, will go up significantly.

Moderna COVID-19 疫苗現已上市，為全球 37 個國家的人們提供保護。隨著世界衛生組織上週五晚上的授權，提供我們疫苗的國家數量將大幅增加。

In the first quarter alone, 102 million doses have been shipped and many tens of millions of people have been fully vaccinated or received their first dose. 12 months ago, in Q1 2020, Moderna had never ran a Phase III clinical study, never gotten a product authorized by a regulator and never made 100 million doses in a single quarter, not even 10 million, not even 1 million doses.

僅在第一季度，就已運送了 1.02 億劑疫苗，數千萬人已完全接種疫苗或接種了第一劑疫苗。 12個月前，即2020年第一季度，Moderna從未進行過III期臨床研究，從未獲得監管機構授權的產品，也從未在單季度生產過1億劑，甚至沒有1000萬劑，甚至沒有100萬劑。

I am very proud of what the Moderna team has achieved, but most importantly, I am very thankful for their impact on the world and the incredible personal sacrifices that our team has made towards protect fellow human beings around the world. This is very humbling, and I'm fortunate to lead Moderna in this moment.

我對 Moderna 團隊所取得的成就感到非常自豪，但最重要的是，我非常感謝他們對世界的影響以及我們團隊為保護世界各地的人類同胞所做出的令人難以置信的個人犧牲。這是非常令人謙卑的，我很幸運能夠在這一刻領導 Moderna。

I'm also thankful for Moderna scientists, engineers, doctors and team members who have worked relentlessly over the last 10 years now to be ready for when the virus emerged in late 2019. We invented technology to produce safe, well-tolerated mRNA vaccines, which made it possible for us to chase the SARS.

我還要感謝Moderna 的科學家、工程師、醫生和團隊成員，他們在過去10 年裡堅持不懈地工作，為2019 年底病毒出現做好了準備。我們發明了生產安全、耐受性良好的mRNA 疫苗的技術，這使得我們有可能追趕非典。

The company achieved revenues of $1.9 billion in Q1 2021 of which $1.7 billion were COVID-19 vaccine product sales. The net income for the period was $1.2 billion. This marks the company's first GAAP profitable quarter in its history after 9 years of operating losses.

該公司在 2021 年第一季度實現收入 19 億美元，其中 17 億美元是 COVID-19 疫苗產品銷售。該期間淨利潤為 12 億美元。這標誌著該公司在經歷了 9 年的經營虧損之後，歷史上第一個按照公認會計原則實現盈利的季度。

At the end of 2021, we had cash and cash investments of $8.2 billion. David will give you more details in a few minutes.

截至 2021 年底，我們擁有現金和現金投資 82 億美元。大衛將在幾分鐘內向您提供更多詳細信息。

We increased our 2021 supply forecast once again. We now believe that we should be able to supply 800 million doses in 2021, and we're still aiming for 1 billion doses over the year. The total advanced purchase agreements signed for delivery in 2021 have been increased to $19.2 billion.

我們再次上調 2021 年供應預測。我們現在認為，我們應該能夠在 2021 年供應 8 億劑疫苗，並且我們的目標仍然是全年提供 10 億劑疫苗。 2021年交付的預購協議總額已增至192億美元。

We are happy to report this morning an interim update to our TeenCOVE study. The initial interim analysis of our Phase II/III TeenCOVE study of mRNA-1273 showed the vaccine efficacy against COVID-19 over 96% and mRNA-1273 was generally well tolerated with no serious safety concern identified to date.

今天早上，我們很高興地報告 TeenCOVE 研究的臨時更新。我們對mRNA-1273 進行的II/III 期Tee​​nCOVE 研究的初步中期分析顯示，疫苗針對COVID-19 的功效超過96%，並且mRNA-1273 總體耐受性良好，迄今為止尚未發現嚴重的安全問題。

We're also on track to start this month the filing of our rolling BLA to the FDA for COVID-19 vaccine mRNA-1273, a type of COVID, we added another first as a company. And that gives the dosing of our first patient with an mRNA for our therapeutics candidate against a rare genetic disease, propionic acidemia a genetic deficiency in the liver with a candidate mRNA-3927.

我們還有望於本月開始向 FDA 提交針對 COVID-19 疫苗 mRNA-1273（一種新冠病毒）的滾動 BLA，這是我們作為一家公司的又一項首次。這為我們的第一例患者提供了針對一種罕見遺傳病丙酸血症（一種候選 mRNA-3927 肝臟遺傳缺陷）的候選療法的 mRNA 患者的劑量。

One of the things that I'm the most excited about is where we are going. The Q1 results highlighted above of the consequence of the last year work and decisions we made. So as I look to where Moderna is going, I get very excited by the level of our increased investments across the board. Using our strong balance sheet to invest to scale Moderna. These 2 numbers, awesome color. In Q1 2021, our R&D investments were approximately 4x higher than the R&D investments in Q1 of last year. Not 4%, not 40%, 4x higher.

我最興奮的事情之一就是我們要去哪裡。上面第一季度的結果強調了去年工作和我們做出的決定的結果。因此，當我展望 Moderna 的發展方向時，我對我們全面增加投資的水平感到非常興奮。利用我們強大的資產負債表進行投資以擴大 Moderna 規模。這兩個數字，顏色真棒。 2021年第一季度，我們的研發投入比去年第一季度的研發投入高出約4倍。不是 4%，不是 40%，高出 4 倍。

For all of you who have known us for many years, Moderna has been built as a digital enterprise since the early days. But we now have the opportunity to do much more and to build new functions like clinical trial operations, pharmacovigilance, commercial, digitally from the get-go. So looking at the next 5 to 10 years, we're investing intensively in digital, automation and AI. Our plan for 2021 is to invest 3x more in digital than in fiscal year 2020.

對於所有認識我們多年的人來說，Moderna 從早期就被打造為一家數字企業。但我們現在有機會做更多的事情，從一開始就建立新的功能，如臨床試驗操作、藥物警戒、商業、數字化。因此，展望未來 5 到 10 年，我們將大力投資數字化、自動化和人工智能。我們 2021 年的計劃是在數字領域的投資比 2020 財年增加 3 倍。

We announced last week that we have decided to invest to increase our 2020 supply to up to 3 billion doses. Let me share with you why we decided to recommend to our Board to invest at that scale. First, let's talk about the science of SARS-CoV-2 virus. New variants of concern continue to emerge around the world. And we believe that over the next 6 months as the southern hemisphere enter its foreign winter, we could see more variants of concern emerge. We have said for right now that we believe booster shots will be needed as we believe that the virus is not going away. We also believe from the scientific standpoint, that the highest efficacy booster over time will be provided by multivalent variant-specific booster.

我們上周宣布，我們決定投資將 2020 年的供應量增加到 30 億劑。讓我與您分享為什麼我們決定建議董事會進行如此規模的投資。首先，我們來談談SARS-CoV-2病毒的科學原理。世界各地不斷出現令人擔憂的新變體。我們相信，在未來 6 個月內，隨著南半球進入外國冬季，我們可能會看到更多不同的擔憂出現。我們目前已經說過，我們認為需要加強注射，因為我們相信病毒不會消失。我們還從科學的角度相信，隨著時間的推移，最高功效的加強劑將由多價變體特異性加強劑提供。

Second, the market has changed quite a lot versus what we knew 6 months ago. First, mRNA vaccines have emerged as the best-in-class vaccines, high efficacy, good tolerability profile, having to scale manufacturing and speed to chase the variants in the clinic. Many companies are still in the clinic with their first-generation vaccine, where we're in a clinic with variant-specific boosters.

其次，與我們 6 個月前的了解相比，市場已經發生了很大變化。首先，mRNA疫苗已成為同類最佳疫苗，功效高、耐受性好，必須擴大生產規模並加快臨床變異的速度。許多公司仍在臨床中使用他們的第一代疫苗，而我們在診所中則使用針對變體的加強疫苗。

More importantly, as we are looking to throw our nets around the world, in the West and in the East, in the North and in the South, we are hearing loud and clear from the market, supply us with more mRNA vaccine for primary series and supply us with more mRNA vaccine in the future for boosters for 2022 and 2023. There is a big shift versus what the market perceived 6 or 9 or 12 months ago, when protein vaccine or adeno vaccines were thought to be the answer to the pandemic. We believe it has become an mRNA market for COVID-19 vaccine.

更重要的是，當我們希望在世界各地撒網時，在西方和東方，在北方和南方，我們聽到市場響亮而明確的聲音，為我們的初級系列提供更多的mRNA疫苗並在未來為我們提供更多mRNA 疫苗，作為2022 年和2023 年的加強疫苗。與6、9 或12 個月前市場的看法相比，情況發生了巨大轉變，當時蛋白質疫苗或腺疫苗被認為是應對大流行的答案。我們相信它已經成為 COVID-19 疫苗的 mRNA 市場。

Third is rollout pipeline. We believe we will bring to market several more products in the next few years as we add to this market demand for COVID-19 boosters vials, flu vaccine as we discussed at the Vaccine Day. And our goal is to have a seasonal flu vaccine combined with COVID variant booster in a single-dose product.

第三是推出管道。我們相信，隨著我們在疫苗日討論的那樣，隨著市場對 COVID-19 加強瓶和流感疫苗的需求增加，我們將在未來幾年內向市場推出更多產品。我們的目標是在單劑量產品中推出季節性流感疫苗和新冠病毒變異加強疫苗。

We saw strong clinical data for RSV vaccine and CMV vaccine. Plus we have 7 programs in clinical studies in 3 therapeutics area and more programs to move from preclinical development to clinical studies in the months to come.

我們看到了 RSV 疫苗和 CMV 疫苗的強有力的臨床數據。此外，我們在 3 個治療領域有 7 個臨床研究項目，未來幾個月還會有更多項目從臨床前開發轉向臨床研究。

So we decided to build capacity to deliver up to 3 billion dose of supply in 2022 to share both the North and the South. We are doubling our drug substance supply in Europe and increasing by 50% of drug substance supply in the U.S. We are, of course, adding filling capacity in the U.S. and Europe at our existing partners, but also adding new ones as we speak, more to come.

因此，我們決定建設能力，在 2022 年提供多達 30 億劑的供應，以供南北雙方共享。我們正在將歐洲的原料藥供應量增加一倍，並將美國的原料藥供應量增加50%。當然，我們正在增加我們現有合作夥伴在美國和歐洲的灌裝能力，但正如我們所說，我們還增加了新的合作夥伴，更多來。

Another clinical feedback we're hearing from the market is that Moderna has a best-in-class mRNA vaccine. Shipment of minus 20 Celsius in storage, not minus 70 celsius. Small cartons of 100 doses. Storage up to 6 months in standard freezer and 4 weeks in regular repurchase temperatures. The only authorized mRNA vaccine that does not require on-site dilution. We believe this is an even more important feature today, but will be more in the future in '21 and '22 and '23 as we move to a booster market decentralized in pharmacies and in a doctor's office.

我們從市場聽到的另一個臨床反饋是 Moderna 擁有一流的 mRNA 疫苗。發貨時儲存溫度為-20攝氏度，而不是-70攝氏度。小紙盒裝 100 劑。在標準冰箱中可保存長達 6 個月，在常規回購溫度下可保存 4 週。唯一授權的無需現場稀釋的mRNA疫苗。我們相信，這在今天是一個更加重要的特徵，但在未來的21 年、22 年和23 年，隨著我們轉向分散在藥房和醫生辦公室的助推器市場，這一特徵將變得更加重要。

We believe we have the best mRNA vaccine authorized, and we continue to improve our product to continue to have a best-in-class product of the mRNA market.

我們相信我們擁有最好的授權 mRNA 疫苗，並且我們將繼續改進我們的產品，以繼續擁有 mRNA 市場的一流產品。

We were delighted to announce this morning the start of a dosing of our first patient in our Phase I/II study with propionic acidemia disease. The study is called Paramount. It is yet another milestone for Moderna. Not only do we have, I believe, the most innovative infectious vaccine clinical pipeline, but we also have therapeutic candidates in clinical studies in oncology, in cardiology and now in a rare genetic disease.

今天早上，我們很高興地宣布，我們開始對丙酸血症疾病 I/II 期研究中的第一位患者進行給藥。這項研究名為“派拉蒙”。這是 Moderna 的又一個里程碑。我相信，我們不僅擁有最具創新性的傳染性疫苗臨床管道，而且我們還在腫瘤學、心髒病學以及現在的罕見遺傳病臨床研究中擁有候選治療藥物。

Let me close my remarks on this familiar slide. We now have 1,500 employees. We have recently incorporated Moderna Japan K.K. And we'll continue to build our commercial network. We will push to Asia Pacific in 2021.

讓我結束對這張熟悉的幻燈片的發言。我們現在有 1,500 名員工。我們最近成立了 Moderna Japan K.K.我們將繼續建立我們的商業網絡。我們將在 2021 年進軍亞太地區。

And given our strong balance sheet of $8.2 billion, we're going to continue to accelerate and invest to allow Moderna to scale and maximize the impact of our broad mRNA platform to help as many people as we can.

鑑於我們 82 億美元的強勁資產負債表，我們將繼續加速和投資，以使 Moderna 能夠擴展並最大限度地發揮我們廣泛的 mRNA 平台的影響，以幫助盡可能多的人。

Let me share our perspective on yesterday afternoon announcement by the United States Trade Ambassador that the U.S. government will ship off waving intellectual property protection for COVID-19 vaccines. We believe this will not help supply more mRNA vaccines to the world any faster in 2021 or in 2022, which is the most critical time of the pandemic. There is no idle mRNA manufacturing capacity in the world. There is no industry of talented individuals who are skilled in the art of making high-quality and high-purity GMP-grade mRNA vaccines. There are no companies who have developed manufacturing processes, purification processes and medical processes that would allow them to quickly run a clinical trial. And if approved by regulators around the world, then provide hundreds of millions or billions of supply of mRNA vaccine.

讓我分享一下我們對昨天下午美國貿易大使宣布美國政府將對 COVID-19 疫苗放棄知識產權保護的看法。我們認為，這無助於在2021年或2022年疫情最關鍵的時期更快地向世界供應更多的mRNA疫苗。全球沒有閒置的mRNA產能。沒有一個行業擁有精通製造高質量和高純度 GMP 級 mRNA 疫苗領域的人才。沒有公司開發出能夠讓他們快速進行臨床試驗的製造工藝、純化工藝和醫療工藝。而如果獲得世界各地監管機構的批准，那麼將提供數億或數十億的mRNA疫苗供應。

We have announced in the company's statement issued October 8, 2020 that during the pandemic, Moderna will not enforce COVID-19-related patents. You can find that statement on our website. We believe that the best way to end the pandemic is what we are currently doing. First, to maximize supply in 2021 to protect as many people as we can.

我們在 2020 年 10 月 8 日發布的公司聲明中宣布，在大流行期間，Moderna 將不會執行與 COVID-19 相關的專利。您可以在我們的網站上找到該聲明。我們相信，結束這一流行病的最佳方法就是我們目前正在做的事情。首先，在 2021 年最大限度地增加供應，以保護盡可能多的人。

Second, to build additional capacity, which we have announced last week to get up to $3 billion of authorized mRNA vaccines for 2022, 2023 and beyond. And third, to continue to adapt the vaccine to have a highest efficacy vaccine with variant-specific booster for which we announced a very encouraging clinical results yesterday.

其次，建立額外的產能，我們上周宣布將在 2022 年、2023 年及以後獲得高達 30 億美元的授權 mRNA 疫苗。第三，繼續對疫苗進行改造，以獲得具有變體特異性增強劑的最高功效疫苗，我們昨天宣布了非常令人鼓舞的臨床結果。

Let me now turn to Corinne to give you a commercial update. Corinne?

現在讓我請 Corinne 為您提供商業更新。科琳娜？

Thank you, Stephane and good morning or good afternoon, everyone. As all of you already know, Moderna's COVID-19 vaccine is our first authorized product. And on the back of it, we have turned into a commercial company very quickly. So today, I'm delighted to give you an update on the commercial progress in the first quarter.

謝謝斯蒂芬，大家早上好或下午好。眾所周知，Moderna 的 COVID-19 疫苗是我們的第一個授權產品。在此基礎上，我們很快就變成了一家商業公司。今天，我很高興向大家介紹第一季度商業進展的最新情況。

I will start with our most recently signed supply agreements, those that occurred in the first quarter and at the beginning of the second quarter this year. I am particularly happy to announce our agreement with COVAX, which will provide access to our vaccine to millions of people in low- and middle-income countries and is in keeping with our global access principles.

我將從我們最近簽署的供應協議開始，這些協議是在今年第一季度和第二季度初簽署的。我特別高興地宣布我們與 COVAX 達成協議，該協議將為中低收入國家的數百萬人提供我們的疫苗，並且符合我們的全球獲取原則。

In total, our COVAX agreement is for 500 million doses for delivery in the 2021 and 2022 period. Specifically, in 2021, Moderna will begin delivery of 34 million doses in the fourth quarter of 2021. COVAX will have an option for an additional 466 million doses in 2022. We are grateful to all the collaborative efforts of CEPI, Gavi, UNICEF, the World Health Organization and the Moderna commercial teams in making this important supply agreement a reality.

總的來說，我們的 COVAX 協議規定在 2021 年和 2022 年期間交付 5 億劑疫苗。具體來說，到 2021 年，Moderna 將在 2021 年第四季度開始交付 3400 萬劑疫苗。COVAX 將可以選擇在 2022 年額外交付 4.66 億劑疫苗。我們感謝 CEPI、Gavi、UNICEF、世界衛生組織和Moderna商業團隊致力於使這一重要的供應協議成為現實。

Moving now to the additional supply agreements signed for both 2021 and '22. We have signed additional supply agreements with Israel for 5.3 million doses in 2022 with an additional option of 17.3 million doses for '22 and '23. And with Switzerland for 7 million doses in 2022 and options for an additional 7 million in late 2022 and '23.

現在討論 2021 年和 22 年簽署的額外供應協議。我們已與以色列簽署了 2022 年 530 萬劑的額外供應協議，並可選擇在 22 年和 23 年供應 1730 萬劑。瑞士將在 2022 年生產 700 萬劑疫苗，並可選擇在 2022 年末和 2023 年再生產 700 萬劑。

We have also signed new deals for '21 delivery with Botswana, Brunei. And in addition, we have also signed an agreement with Zuellig Pharma, our distribution partner,in Southeast Asia, Hong Kong, Macau and Taiwan.

我們還與博茨瓦納、文萊簽署了 '21 交付的新協議。此外，我們還與東南亞、港澳台地區的分銷合作夥伴Zuellig Pharma簽署了協議。

In total, we announced advanced purchase agreements totaling 845 million doses to be delivered in 2021 to the countries that are listed here on the slide. And we continue to have discussions with countries, who those we have already contracted with and new countries for supply in 2022 and beyond.

總的來說，我們宣布了總計 8.45 億劑的預購協議，將於 2021 年向幻燈片上列出的國家交付。我們將繼續與已簽訂合同的國家以及 2022 年及以後供應的新國家進行討論。

In our discussions, as Stephane said, we are hearing consistently from governments that in their view, there is no other technology that provides the high efficacy of mRNA vaccines and the speed necessary to adapt to variants, while at the same time, allowing reliable scalability of manufacturing. We are grateful for the trust placed in us from the various governments we have signed agreements with, and we look forward to supplying the vaccine to other countries and helping end the pandemic and getting ahead of variance.

正如 Stephane 所說，在我們的討論中，我們不斷聽到各國政府表示，在他們看來，沒有其他技術能夠提供 mRNA 疫苗的高效性和適應變體所需的速度，同時允許可靠的可擴展性的製造。我們感謝與我們簽署協議的各國政府對我們的信任，我們期待著向其他國家提供疫苗，幫助結束疫情並戰勝分歧。

Let me now turn to product sales. Our first -- our product sales for the first quarter of this year were $1.73 billion and were recorded for the delivery of 102 million doses. Product sales in the U.S. were approximately $1.4 billion and sales outside of the U.S. to the EU, Canada, Switzerland, Israel and Singapore were approximately $400 million for the 14 million doses delivered in the first quarter.

現在讓我談談產品銷售。我們的第一——今年第一季度的產品銷售額為 17.3 億美元，交付量為 1.02 億劑。第一季度交付的 1400 萬劑疫苗在美國的產品銷售額約為 14 億美元，在美國以外的歐盟、加拿大、瑞士、以色列和新加坡的銷售額約為 4 億美元。

In the U.S., we have successfully completed the delivery of the first 100 million doses to the U.S. government within 100 days of emergency use authorization. And we expect to complete the delivery of the second 100 million doses to the United States government before the end of the second quarter.

在美國，我們在緊急使用授權後的 100 天內成功完成了向美國政府交付首批 1 億劑疫苗。我們預計在第二季度末之前完成向美國政府交付第二個1億劑疫苗。

As you know, the U.S. production started earlier and is roughly 1 quarter ahead in production ramp. As such, in the second quarter of '21, we expect the ex-U.S. ramp to be similar to that of the U.S. ramp in the first quarter.

如您所知，美國的生產開始較早，產量增長大約領先一個季度。因此，我們預計 21 年第二季度美國以外的地區增長與美國第一季度的增長相似。

To close, I want to reiterate that as we continue to produce and roll out vaccines into the global market, we are humbled and proud to be part of the solution.

最後，我想重申，隨著我們繼續生產疫苗並將其推向全球市場，我們為成為解決方案的一部分而感到謙卑和自豪。

I will now turn the call over to David Meline.

我現在將把電話轉給大衛·梅林。

Okay. Thank you, Corinne. Today, as with our last earnings call, we are presenting our results primarily on a U.S. GAAP basis. In some cases, we also provide additional detail to provide greater clarity on underlying trends. With this background, we are providing an analysis of actual 2021 first quarter results, along with an updated view of key drivers of financial performance going forward.

好的。謝謝你，科琳娜。今天，與我們上次的財報電話會議一樣，我們主要根據美國公認會計原則（U.S. GAAP）公佈我們的業績。在某些情況下，我們還會提供更多詳細信息，以便更清楚地了解潛在趨勢。在此背景下，我們對 2021 年第一季度的實際業績進行了分析，並對未來財務業績的關鍵驅動因素進行了更新。

Turning to Slide 18. Total revenue was $1.9 billion in the first quarter of 2021 compared to $8 million in Q1 of last year. Following our first-ever product sales of $200 million in December 2020, we recorded product sales of $1.7 billion for our COVID-19 vaccine in the first quarter of 2021.

轉向幻燈片 18。2021 年第一季度的總收入為 19 億美元，而去年第一季度的總收入為 800 萬美元。繼 2020 年 12 月首次產品銷售額達到 2 億美元之後，我們的 COVID-19 疫苗產品銷售額在 2021 年第一季度達到 17 億美元。

Grant and collaboration revenue increased to $204 million in Q1, primarily due to increases in grant revenue from BARDA to accelerate development of our COVID-19 vaccine.

第一季度的撥款和合作收入增加至 2.04 億美元，這主要是由於 BARDA 為加速我們的 COVID-19 疫苗的開發而增加的撥款收入。

Cost of sales were $193 million in the first quarter, benefiting substantially from previously expensed pre-commercial inventory costs, which I will discuss in more detail on a later slide.

第一季度的銷售成本為 1.93 億美元，很大程度上受益於之前支出的商業前庫存成本，我將在後面的幻燈片中更詳細地討論這一點。

Research and development expenses were $401 million for Q1 2021 compared to $115 million for the same period in 2020. The higher spend 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 pharmacovigilance activities related to our COVID-19 vaccine also contributed to the year-on-year expense increase.

2021 年第一季度的研發費用為4.01 億美元，而2020 年同期為1.15 億美元。支出增加是由於COVID-19 疫苗臨床開發活動增加，包括我們宣布的圍繞加強疫苗、變體特異性疫苗和多價候選疫苗的努力。員工人數的增加以及與我們的 COVID-19 疫苗相關的藥物警戒活動也導致了費用同比增加。

Selling, general and administrative expenses were $77 million for Q1 2021 compared to $24 million for the same period in the prior year. The growth in spending was driven by increases in personnel, outside services and costs associated with commercialization of our COVID-19 vaccine globally.

2021 年第一季度的銷售、一般和管理費用為 7700 萬美元，而上年同期為 2400 萬美元。支出的增長是由於人員、外部服務以及與我們的 COVID-19 疫苗在全球商業化相關的成本的增加所推動的。

Our provision for income taxes was $39 million in Q1 2021, reflecting a benefit from the utilization of our net operating loss carryforward as well as discrete items. I will provide further context on the following slides.

2021 年第一季度，我們的所得稅撥備為 3900 萬美元，反映出利用我們的淨營業虧損結轉以及離散項目帶來的收益。我將在下面的幻燈片中提供更多背景信息。

We recorded net income of $1.2 billion for Q1 of this year compared to a net loss of $124 million in the same period of last year. Earnings per share on a diluted basis was $2.84. Please note that our share count on a diluted basis now also includes the effect of outstanding options and RSUs as we began to be profitable. Previously, when we were in a net loss position, basic and reported diluted number of shares were the same.

今年第一季度，我們錄得淨利潤 12 億美元，而去年同期淨虧損 1.24 億美元。攤薄後每股收益為 2.84 美元。請注意，隨著我們開始盈利，我們的攤薄股份數量現在還包括未償還期權和 RSU 的影響。此前，當我們處於淨虧損狀態時，基本股數和報告的稀釋後股數是相同的。

Turning to cash and selected cash flow information on Slide 19. We ended Q1 2021 with cash and investments of $8.2 billion compared to $5.2 billion at the end of Q4 2020. The increase is driven by our commercial sales and additional customer deposits received in the first quarter for future purchases of our COVID-19 vaccine. Net cash provided by operating activities was $2.97 billion in Q1 of this year compared to net cash used in operating activities of $106 million in Q1 of last year. The reversal from net operating cash outflow to cash inflow was driven by our commercial market entry for the entire quarter.

轉向幻燈片19 上的現金和選定的現金流量信息。截至2021 年第一季度，我們的現金和投資為82 億美元，而2020 年第四季度末為52 億美元。這一增長是由我們的商業銷售和第一季度收到的額外客戶存款推動的。未來購買我們的 COVID-19 疫苗的季度。今年第一季度經營活動提供的現金淨額為 29.7 億美元，而去年第一季度經營活動使用的現金淨額為 1.06 億美元。從淨經營現金流出到現金流入的逆轉是由我們整個季度進入商業市場推動的。

Similar to last quarter, before providing an updated financial framework for the remainder of 2021, let me summarize a few areas from our Q1 results that are important to keep in mind when modeling expected 2021 financial performance.

與上季度類似，在提供 2021 年剩餘時間的更新財務框架之前，讓我總結一下第一季度結果中的幾個領域，在對 2021 年預期財務業績進行建模時需要牢記這些領域。

Starting with product sales on Slide 20. We started last year to build 2 distinct supply chains, one in the U.S. and one outside the U.S. for rest of world markets. Our supply chain scale up in the U.S. was roughly 1 quarter in advance of our ex U.S. supply chain, which is reflected in the geographic sales mix in Q1. As we move forward in Q2, the ex U.S. supply chain is also ramping up toward full capability.

從幻燈片 20 上的產品銷售開始。我們從去年開始建立 2 條不同的供應鏈，一條在美國，一條在美國以外，面向世界其他市場。我們在美國的供應鏈規模比我們在美國以外的供應鏈提前了大約 1 個季度，這反映在第一季度的地理銷售組合中。隨著第二季度的進展，美國以外的供應鏈也正在朝著全面產能的方向發展。

Turning to Slide 21. Cost of sales includes the cost of goods manufactured, logistics and warehousing costs as well as third-party royalty costs. We began capitalizing our COVID-19 vaccine inventory costs in December of 2020, following the COVID-19 vaccine emergency use authorization based upon our expectation that these inventory costs would be recoverable through commercialization of the vaccine. Prior to the authorization of our COVID-19 vaccine, inventory costs were recorded as research and development expenses in the period incurred. We expensed $242 million of prelaunch inventory costs in 2020 and started 2021 with the remaining balance of $187 million of 0 cost inventory. Almost the entire balance, or $184 million was sold and benefited our cost of sales in Q1 of this year, and hence, will not further impact future quarters in a material way. If inventory sold during the first quarter was valued at actual cost, our cost of sales would have been $377 million or 22% of our product sales somewhat favorable to what we expected, driven by favorable yields in our U.S. production facilities.

轉向幻燈片 21。銷售成本包括商品製造成本、物流和倉儲成本以及第三方特許權使用費。在獲得 COVID-19 疫苗緊急使用授權後，我們開始將 COVID-19 疫苗庫存成本資本化，因為我們預計這些庫存成本將通過疫苗商業化來收回。在我們的 COVID-19 疫苗獲得授權之前，庫存成本在發生期間記錄為研發費用。我們在 2020 年支出了 2.42 億美元的啟動前庫存成本，並從 2021 年開始，剩餘的餘額為 1.87 億美元的零成本庫存。幾乎全部餘額（即 1.84 億美元）已售出，並有利於我們今年第一季度的銷售成本，因此不會對未來幾個季度產生進一步的重大影響。如果第一季度銷售的庫存按實際成本計價，我們的銷售成本將為 3.77 億美元，佔產品銷售額的 22%，這在我們美國生產設施良好產量的推動下，略好於我們的預期。

Now turning to our cash and investment position on Slide 22. The cash and investment balance reported as of March 31 was $8.2 billion, up from $5.2 billion as of December 31, 2020. The increase is primarily driven by the net increase in customer deposits for future product supply of COVID-19 vaccine. The net balance of cash customer deposits increased from $2.8 million at the end of December 2020 to $5.6 billion at the end of Q1 '21.

現在轉向幻燈片22 上的現金和投資頭寸。截至3 月31 日報告的現金和投資餘額為82 億美元，高於截至2020 年12 月31 日的52 億美元。這一增長主要是由於客戶存款淨增加所致COVID-19 疫苗的未來產品供應。現金客戶存款淨餘額從 2020 年 12 月末的 280 萬美元增至 21 年第一季度末的 56 億美元。

Lastly, let me comment on tax-related items on Slide 23. The significant investments in our research, development and start-up activities to develop the mRNA platform over the last decade have resulted in net operating loss carryforwards, with a balance of $2.3 billion at the end of 2020. As of December 31, 2020, we maintained a full valuation allowance against our deferred tax assets related to these loss carryforwards. We performed a valuation allowance assessment during each reporting period based on the latest available financial information and outlook.

最後，讓我評論一下幻燈片 23 上的稅務相關項目。過去十年來，我們為開發 mRNA 平台而對研發和啟動活動進行了大量投資，導致淨營業虧損結轉，餘額為 23 億美元截至2020年底。截至2020年12月31日，我們對與這些損失結轉相關的遞延稅資產保留了全額估值備抵。我們根據最新的財務信息和前景在每個報告期內進行了估值備抵評估。

After considering the weight of available evidence, both positive and negative, we concluded that as of March 31, it is more likely than not that the company will be able to realize the substantial majority of its net deferred tax assets. This analysis included not only our strong first quarter results, but also our April activity. The majority of the valuation allowance will flow through the P&L over the course of 2021 in our effective tax rate prorated based on the cadence of our expected pretax quarterly earnings.

在考慮了現有證據（包括正面和負面證據）的權重後，我們得出的結論是，截至 3 月 31 日，該公司很可能能夠實現其大部分淨遞延稅資產。該分析不僅包括我們強勁的第一季度業績，還包括我們四月份的活動。大部分估值津貼將在 2021 年期間按照我們的有效稅率流入損益表，該稅率根據我們預期的稅前季度收益的節奏按比例分配。

We also recorded 2 discrete benefits in our tax provision in Q1, which lowered our first quarter tax rate. The first benefit related to the valuation allowance release for the portion of deferred tax assets, which we expect to utilize in future years. The second related to the excess tax benefits associated with stock-based compensation.

我們還在第一季度的稅收撥備中記錄了兩項離散的好處，這降低了我們第一季度的稅率。第一個好處與我們預計在未來幾年使用的遞延所得稅資產部分的估值備抵釋放有關。第二個與股票薪酬相關的超額稅收優惠有關。

Turning now to the 2021 updated financial framework on Slide 24. Signed advanced purchase agreements for expected delivery in 2021 reflect a current full year total of $19.2 billion in anticipated product sales including doses that have been delivered and recognized as revenue in Q1.

現在轉向幻燈片24 上的2021 年更新財務框架。已簽署的預計2021 年交付的預購協議反映了當前全年預期產品銷售額總計192 億美元，其中包括已交付並在第一季度確認為收入的劑量。

Based on continuous progress to ramp up available supply capacity in our network, we have raised the lower end of our global manufacturing plan for 2021 from 700 million to 800 million doses at the 100-microgram dose level. Our manufacturing team and our partners are still working to supply up to 1 billion doses for 2021. Further, we continue to expect a range of deliveries in Q2 2021 of 200 million to 250 million doses.

基於不斷提高我們網絡中的可用供應能力，我們已將 2021 年全球生產計劃的下限從 100 微克劑量水平的 7 億劑提高到 8 億劑。我們的製造團隊和合作夥伴仍在努力在 2021 年供應多達 10 億劑疫苗。此外，我們仍然預計 2021 年第二季度的交付量將達到 2 億至 2.5 億劑。

Our total cost of sales includes the cost of manufacturing, logistics and warehousing and third-party royalties. For 2021, we continue to model average total cost of sales as a percent of product sales to be approximately 20% for the full year with some variation quarter-by-quarter largely driven by average selling price going forward.

我們的總銷售成本包括製造、物流和倉儲成本以及第三方特許權使用費。對於 2021 年，我們繼續將全年平均總銷售成本佔產品銷售額的百分比預測為約 20%，逐季度出現一些變化，這主要是由未來平均銷售價格驅動的。

Now let me comment on planned R&D and SG&A expenses. Q1 expenses of approximately $0.5 billion were stable compared to the underlying Q4 2020 expense run rate on a like-for-like basis.

現在讓我評論一下計劃的研發和銷售、一般行政費用。與 2020 年第四季度的基本同比費用運行率相比，第一季度費用約為 5 億美元，保持穩定。

In Q1, our actual expenses were lower than the internal forecast primarily driven by the timing of clinical development and commercial activities and related costs. We now expect a notable expense trend increase starting in Q2 on a quarter-over-quarter basis for the remainder of this year.

第一季度，我們的實際費用低於內部預測，主要是由於臨床開發和商業活動的時間安排以及相關成本所致。我們現在預計，從第二季度開始，今年剩餘時間的費用將出現環比顯著增長的趨勢。

Based on better visibility of the utilization of our accumulated net operating loss carryforward, expected global sales mix and the mentioned discrete benefits in Q1, we now expect our all-in 2021 tax rate to be in the low teens. This compares to our previous forecast in the mid-teen range. This forecast is based on current U.S. tax policy in effect and does not include any future potential discrete benefits related to stock-based compensation. We will update this view as our business evolves further.

基於對我們累計淨營業虧損結轉的利用率、預期全球銷售組合以及第一季度提到的離散收益的更好可見性，我們現在預計 2021 年的總體稅率將在十幾歲以下。與我們之前的預測相比，該預測處於青少年範圍內。該預測基於美國現行的稅收政策，不包括與股票薪酬相關的任何未來潛在的離散福利。隨著我們業務的進一步發展，我們將更新這一觀點。

Finally, regarding capital investments, we are raising our forecast for capital investment from our previous range of $350 million to $400 million for 2021 to $450 million to $550 million, including the planned capacity expansion investments as announced on April 29.

最後，關於資本投資，我們將 2021 年資本投資預測從之前的 3.5 億至 4 億美元範圍提高到 4.5 億至 5.5 億美元，其中包括 4 月 29 日宣布的計劃產能擴張投資。

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

我關於財務業績的評論到此結束，現在我將電話轉給斯蒂芬。

Thank you, David. I'll begin with an overview of our COVID-19 strategy against variants of concern and the initial data from our Phase II booster vaccination study before ending with a summary of the rest of our pipeline. And before I go into the data, a reminder that our booster strategy is evaluating single-dose booster vaccinations with 3 different mRNA vaccines: 50 micrograms of mRNA-1273; 50 micrograms of mRNA-1273.351, both of which have data available today and what I will discuss in just a moment; and a multivalent booster vaccine candidate, which combines a 50-50 mix of mRNA-1273 and mRNA-1273.351 in a single vaccine.

謝謝你，大衛。我將首先概述我們針對相關變體的 COVID-19 策略以及我們的 II 期加強疫苗接種研究的初始數據，然後總結我們的其餘產品線。在我討論數據之前，提醒一下我們的加強策略正在評估使用 3 種不同 mRNA 疫苗的單劑量加強疫苗接種：50 微克 mRNA-1273；50 微克 mRNA-1273； 50 微克 mRNA-1273.351，這兩個數據今天都有可用的數據，我稍後將討論這些數據；以及一種多價加強疫苗候選方案，它將 mRNA-1273 和 mRNA-1273.351 的 50-50 混合物組合在單一疫苗中。

In addition, we're also evaluating a lower 20-microgram dose of mRNA-1273.351. Data from the multivalent booster and the 20-microgram booster of 351 will be shared when available.

此外，我們還在評估較低劑量的 20 微克 mRNA-1273.351。來自多價加強劑和 351 20 微克加強劑的數據將在可用時進行共享。

And with that backdrop, let's move to the data. Starting with safety, local and systemic adverse events within 7 days after a booster dose of either -1273 or -1273.351 were generally comparable to those observed after the second dose of -1273 in our previously reported Phase II study and our Phase III COVE study. The majority of the events were mild or moderate in severity and grade 3 events occurred with a frequency of approximately 15% in participants who received -1273 and approximately 10% in participants who received -1273.351. The most commonly reported solicited local events were injection site pain and the most commonly reported systemic events were fatigue, headache, myalgia and arthralgia. There were no grade 4 events reported.

在這個背景下，讓我們轉向數據。從安全性開始，-1273 或 -1273.351 加強劑量後 7 天內的局部和全身不良事件通常與我們之前報導的 II 期研究和 III 期 COVE 研究中第二劑 -1273 後觀察到的不良事件相當。大多數事件的嚴重程度為輕度或中度，接受 -1273 的參與者發生 3 級事件的頻率約為 15%，接受 -1273.351 的參與者的發生頻率約為 10%。最常報告的局部事件是注射部位疼痛，最常報告的全身事件是疲勞、頭痛、肌痛和關節痛。沒有報告 4 級事件。

On the next slide, are figures from 2 papers. The figure on the left-hand side were published in the New England Journal of Medicine and show the difference in neutralization of SARS-CoV-2 pseudoviruses in serum samples 1 week after vaccination with a primary series of mRNA-1273. Recall that there was a sixfold decrease in neutralization titers against the B.1.351 variant, the variant first identified in the Republic of South Africa; and a three-fold drop in titers against P.1, the variant first described in Brazil. And again, as a reminder, these neutralizing titer levels were from serum samples 1 week after the second dose of the primary vaccine series of mRNA-1273. So essentially, these titers are close to peak levels.

下一張幻燈片上是兩篇論文中的數據。左圖發表在《新英格蘭醫學雜誌》上，顯示了接種初級系列 mRNA-1273 後 1 週，血清樣本中 SARS-CoV-2 假病毒的中和效果差異。回想一下，針對 B.1.351 變體（該變體首先在南非共和國發現）的中和滴度降低了六倍；針對 P.1 的滴度下降了三倍，P.1 是巴西首次描述的變體。再次提醒一下，這些中和滴度水平來自 mRNA-1273 初級疫苗系列第二劑後 1 週的血清樣本。因此本質上，這些滴度接近峰值水平。

On the right-hand side of the slide is a figure from the preprint manuscript of our initial results from our Phase II study posted yesterday at Bio Archive. The figures show the neutralization titer levels of the participants in our Phase II booster study immediately before their booster vaccinations.

幻燈片的右側是我們昨天在 Bio Archive 上發布的第二階段研究初步結果的預印本手稿中的一張圖。這些數字顯示了我們第二階段加強疫苗研究中參與者在加強疫苗接種前的中和滴度水平。

A reminder that these individuals were previously vaccinated with a primary series of mRNA-1273 in either our Phase II or Phase III studies, roughly 6 to 8 months prior to enrolling in this booster study.

提醒一下，這些人之前在我們的 II 期或 III 期研究中接種了 mRNA-1273 的初級系列疫苗，大約在參加本次加強研究之前 6 至 8 個月。

At this time point, titers against wild-type SARS-CoV-2 remained high with almost all participants having detectable titers. But titers against B.1.351 and P1, the variants of concern were much lower. In fact, approximately half of participants had titers below the assays limit of quantitation at this time point.

此時，針對野生型 SARS-CoV-2 的滴度仍然很高，幾乎所有參與者都具有可檢測到的滴度。但針對 B.1.351 和 P1（受關注變體）的滴度要低得多。事實上，此時大約一半的參與者的滴度低於定量分析極限。

So it is clear that waning of titers is apparent, both with time and that lower titers against variants of concern lead to more rapid loss of neutralizing activity.

因此，很明顯，滴度隨著時間的推移而明顯減弱，並且針對所關注的變體的較低滴度會導致中和活性更快喪失。

Turning to the next slide. The data shows that 2 weeks after booster vaccines of either mRNA-1273 or -1273.351 neutralizing tighter levels increased against both the wild-type virus as well as the B.1.351 and P1 variants of concern. In fact, following boost, geometric mean titers against the 3 variants tested increased to levels similar to or higher than previously reported peak titers against the ancestral strain following primary vaccination.

轉到下一張幻燈片。數據顯示，在接種加強疫苗 2 週後，針對野生型病毒以及相關 B.1.351 和 P1 變體的 mRNA-1273 或 -1273.351 中和水平更嚴格地增加。事實上，在加強接種後，針對所測試的 3 種變體的幾何平均滴度增加到類似於或高於先前報告的初次接種後針對祖先菌株的峰值滴度的水平。

When looking specifically at the GMTs of the different strains, we achieved levels of 1,400 after booster vaccination with mRNA-1273.351 against the 351 variant. This compares against the GMT of 864 when boosting with mRNA-1273.

當具體觀察不同毒株的 GMT 時，我們在針對 351 變體的 mRNA-1273.351 加強疫苗接種後達到了 1,400 的水平。與使用 mRNA-1273 加強時的 GMT 864 進行比較。

Vaccination with mRNA-1273.351 was more effective at narrowing the gap in neutralizing titers between wild-type and B.1.351 viruses relative to boosting with mRNA-1273.

相對於用 mRNA-1273 進行加強接種，用 mRNA-1273.351 進行疫苗接種在縮小野生型病毒和 B.1.351 病毒之間中和滴度方面的差距更有效。

Now we're encouraged by this initial data, and we're excited to see additional data over time from these arms as well as the data from the multivalent arm and a lower dose arm of mRNA-1273.351.

現在我們對這個初始數據感到鼓舞，並且我們很高興看到隨著時間的推移這些臂的更多數據以及來自 mRNA-1273.351 多價臂和較低劑量臂的數據。

On the next slide, I would like to highlight one last comparison from the manuscript. On the left hand is a sample of participants from the Phase I study and they're neutralizing titers against ancestral strain following a primary vaccination series with mRNA-1273. GMT is achieved in this assay approximately 1,500.

在下一張幻燈片上，我想強調一下手稿的最後一個比較。左邊是第一階段研究的參與者樣本，他們在使用 mRNA-1273 進行初次疫苗接種系列後，正在中和針對祖先菌株的滴度。在此測定中，GMT 約為 1,500。

On the right-hand side is a reproduction of the data we just spoke through, looking at neutralizing titers, and I'm specifically highlighting the neutralizing titers against the B.1.351 variant of concern. A booster dose of 50 micrograms of mRNA-1273, the top bar, was able to increase titers to a level of 864 in this study. That compares with a booster dose of 50 micrograms of 1273.351, which was able to get to titers against the variant of concern as high as 1,400 in the study. We'll continue to closely watch this data, and as I mentioned a moment ago, look forward to subsequent updates and time points.

右側是我們剛才談到的數據的複制，查看中和滴度，我特別強調了針對所關注的 B.1.351 變體的中和滴度。在本研究中，50 微克 mRNA-1273（頂欄）的加強劑量能夠將滴度提高到 864 的水平。相比之下，50 微克的 1273.351 加強劑量能夠在研究中達到高達 1,400 的針對關注變體的滴度。我們將繼續密切關注這個數據，正如我剛才提到的，期待後續的更新和時間點。

On Slide 31 is a snapshot of our vaccine development candidates that are in or entering the clinic. I'll highlight a few. Our CMV vaccine is on track to start a pivotal Phase III study in 2021. Our Zika vaccine is expected to begin a Phase II study also in 2021. Our hMPV/PIV3 respiratory combo vaccine is currently enrolling in toddlers. And at our Vaccines Day last month, we announced positive interim Phase I data from our RSV vaccine, mRNA-1345. This continues in pediatric and older adult cohorts of that Phase I study are still enrolling.

第 31 張幻燈片是我們正在或進入診所的候選疫苗開發的快照。我將重點介紹一些。我們的 CMV 疫苗有望於 2021 年開始關鍵的 III 期研究。我們的 Zika 疫苗預計也將於 2021 年開始 II 期研究。我們的 hMPV/PIV3 呼吸道組合疫苗目前正在幼兒中招募。在上個月的疫苗日上，我們宣布了 RSV 疫苗 mRNA-1345 的積極中期 I 期數據。這一第一階段研究的兒童和老年人群體的情況仍在繼續，目前仍在招募中。

Finally, within our flu vaccine program, we expect a Phase I study of mRNA-1010 to begin in 2021.

最後，在我們的流感疫苗計劃中，我們預計 mRNA-1010 的 I 期研究將於 2021 年開始。

Outside of vaccines, we have 7 clinical proof-of-concept trials ongoing across 4 modalities. Our VEGF program partnered with AstraZeneca is enrolling in a Phase II. Our personalized cancer vaccine program partnered with Merck is also enrolling in a Phase II trial. And KRAS, our second program partnered with Merck is ongoing in a Phase I study.

除疫苗外，我們正在進行 4 種模式的 7 項臨床概念驗證試驗。我們與阿斯利康合作的 VEGF 項目正在進入第二階段。我們與默克公司合作的個性化癌症疫苗項目也正在進行二期試驗。 KRAS 是我們與默克合作的第二個項目，目前正在進行第一階段研究。

Within intratumoral immuno-oncology, our Phase II dose expansion in OX40 ligand, Phase I Triplet and Phase I IL-2 study, which is partnered with AstraZeneca, are all still ongoing.

在腫瘤內免疫腫瘤學領域，我們與阿斯利康合作的 OX40 配體 II 期劑量擴展、I 期三聯體和 I 期 IL-2 研究仍在進行中。

Finally, as Stephane mentioned, we are pleased to have started dosing in the Paramount study in propionic acidemia.

最後，正如 Stephane 提到的，我們很高興在派拉蒙研究中開始對丙酸血症進行給藥。

On Slide 33, you can see our full development pipeline. In addition to our large portfolio of infectious disease vaccines, we now have 7 therapeutic programs in the clinic.

在幻燈片 33 上，您可以看到我們完整的開發流程。除了我們大量的傳染病疫苗之外，我們現在還有 7 個臨床治療項目。

I'll now turn the call over to Stephane. Thank you so much.

我現在將電話轉給斯蒂芬。太感謝了。

Thank you, Stephen, Corinne and David. Our 2021 advanced purchase agreement signed have now been increased to $19.2 billion. As we look into 2022, we're investing to distribute and dose supply capacity because we believe the market need -- could be greater in 2022 than in 2021.

謝謝斯蒂芬、科琳和大衛。我們簽署的2021年預購協議現已增至192億美元。展望 2022 年，我們正在投資分配和增加供應能力，因為我們相信 2022 年的市場需求可能會比 2021 年更大。

First, we already have countries signing APAs for 2022 for prime series for children but also for variant-specific boosters. Israel last week and Switzerland this morning.

首先，我們已經有一些國家簽署了 2022 年兒童 Prime 系列以及特定變種加強版的 APA。以色列上周和瑞士今天早上。

If you recall, there were some of the first countries who signed APAs in 2020. And again, these countries are ahead of the game for 2022 and 2023.

如果您還記得，有一些國家在 2020 年率先簽署了 APA。同樣，這些國家在 2022 年和 2023 年也處於領先地位。

Second, with the COVAX partnership announced Monday, we anticipate to supply up to 466 million doses in 2022.

其次，隨著周一宣布的 COVAX 合作夥伴關係，我們預計 2022 年將供應多達 4.66 億劑疫苗。

Third, we're having active discussions with all the governments that have signed 2021 APAs with Moderna. For new APAs for 2022 deliveries, again, prime series but also boosters.

第三，我們正在與與 Moderna 簽署 2021 年 APA 的所有政府進行積極討論。對於 2022 年交付的新 APA，同樣是 Prime 系列，但也包括助推器。

Fourth, we're having numerous discussions with government that do not have 2021 APAs with Moderna because we cannot supply them in 2021 unfortunately. But many of these governments are already asking us to enter into 2022 APAs because they want high efficacy mRNA vaccines that are easy to store. This is why we decided to invest for more supply in 2022. We believe from our current deals and current discussions that the market wants more supply from us in 2022 than we can supply in 2021.

第四，我們正在與沒有與 Moderna 簽訂 2021 年 APA 的政府進行多次討論，因為不幸的是我們無法在 2021 年提供它們。但其中許多政府已經要求我們加入 2022 年 APA，因為他們想要易於儲存的高效 mRNA 疫苗。這就是我們決定在 2022 年投資更多供應的原因。從我們目前的交易和當前的討論來看，我們認為，市場希望我們在 2022 年提供的供應量超出了我們 2021 年的供應量。

As we look at the next 5 to 10 years, we have the most innovative vaccine pipeline in the industry. And we're investing more in research to increase our impact by bringing to the clinic, more innovative vaccines against viruses that hurt humans. We are now in the clinic in 3 therapeutic areas: oncology, cardiology and rare disease and soon, we should be in the clinic in autoimmune disease as well. We are continuing to innovate and invest in science, like, for example, for delivering mRNA in the lung with our partner, Vertex.

展望未來 5 到 10 年，我們擁有業內最具創新性的疫苗產品線。我們正在加大研究投入，通過將針對傷害人類的病毒的更具創新性的疫苗引入臨床，來提高我們的影響力。我們現在在三個治療領域開展臨床工作：腫瘤學、心髒病學和罕見疾病，很快我們也應該進入自身免疫性疾病的臨床工作。我們正在繼續創新並投資於科學，例如與我們的合作夥伴 Vertex 一起在肺部輸送 mRNA。

As we continue to prepare Moderna to scale and to have 10x more impact, we're investing aggressively. We are accelerating our investments in digital, automation and AI.

隨著我們繼續幫助 Moderna 擴大規模並使其影響力擴大 10 倍，我們正在積極投資。我們正在加速對數字化、自動化和人工智能的投資。

From a spend of $27 million in 2019, we invested around $60 million in 2020 in digital. We're planning to almost triple that $170 million in 2021. We're investing across the world in R&D to ensure high quality to accelerate the pace of learning and to ensure we can transform clinical operations. We're investing in digital to ensure high-quality, high scalability for manufacturing. We are building commercial so that we can commercialize our pipeline in a highly efficient and effective manner. We want to change the big pharma paradigm of large, inefficient and expensive sales force and advertising spend to promote me-too drugs. Our pipeline is first-in-class medicine that patients and doctors are waiting for.

2019 年我們在數字領域的支出為 2700 萬美元，2020 年我們在數字領域的投資約為 6000 萬美元。我們計劃在 2021 年將這一 1.7 億美元增加近兩倍。我們在全球範圍內投資研發，以確保高質量，加快學習速度，並確保我們能夠改變臨床操作。我們正在數字化方面進行投資，以確保製造的高質量、高可擴展性。我們正在建設商業項目，以便我們能夠以高效和有效的方式將我們的管道商業化。我們希望改變大型製藥公司的模式，即龐大、低效且昂貴的銷售隊伍和廣告支出來推廣仿製藥。我們的產品線是患者和醫生都在等待的一流藥物。

We want to enable our corporate functions, HR, legal, finance and so on to scale without creating large corporate organization.

我們希望在不創建大型企業組織的情況下擴展我們的企業職能、人力資源、法律、財務等。

I'm also excited that we are launching an AI Academy. Today, we have some exciting pockets of excellence in AI across the company. But AI is not yet part of our DNA. The reason is simple, most companies don't do AI. So as we grow and hire new talent, they have great skills in their heart, but few have been exposed to AI in their previous company. We want AI to be how we run the business in science, in clinical development, in manufacturing quality in commercial, in HR and finance, everywhere.

我也很高興我們即將成立人工智能學院。如今，我們公司在人工智能領域擁有一些令人興奮的卓越人才。但人工智能還不是我們 DNA 的一部分。原因很簡單，大多數公司不做AI。因此，當我們成長並僱用新人才時，他們內心擁有出色的技能，但很少有人在以前的公司接觸過人工智能。我們希望人工智能成為我們在科學、臨床開發、製造質量、商業、人力資源和財務等各個領域開展業務的方式。

It is the same change management revolution as 20 to 30 years ago when personal computers entered the workforce. We want everything at Moderna to understand and use AI in everything we do. AI will become part of our DNA.

這與 20 至 30 年前個人電腦進入勞動力市場時的變革管理革命相同。我們希望 Moderna 的所有員工都能理解並在我們所做的一切事情中使用人工智能。人工智能將成為我們 DNA 的一部分。

As many of you know, we have built integrated digital system connected to each other. And as we have more systems, we get more data. As we get more data, we learn faster. And we keep building and creating a network cycle. Between our strong balance sheet, our mRNA platform, our team, our culture and our digital infrastructure, I believe our belief to scale Moderna is unique in the biopharmaceutical industry.

眾所周知，我們已經建立了相互連接的集成數字系統。隨著我們擁有更多系統，我們獲得更多數據。當我們獲得更多數據時，我們學得更快。我們不斷構建和創造一個網絡循環。在我們強大的資產負債表、我們的 mRNA 平台、我們的團隊、我們的文化和我們的數字基礎設施之間，我相信我們擴展 Moderna 的信念在生物製藥行業是獨一無二的。

As part of scaling Moderna, there is software, better so very value added. Many of you were at the opening of a Norwood manufacturing site in July 2018 or you came to visit after the opening. Our building is around 200,000 square feet. We call it Moderna Technology Center South or MTC South.

作為擴展 Moderna 的一部分，有軟件，更好，所以非常增值。你們中的許多人都參加過 2018 年 7 月諾伍德製造工廠的開業典禮，或者在開業後前來參觀。我們的建築面積約為 200,000 平方英尺。我們將其稱為 Moderna 南技術中心或 MTC 南。

In 2020, we added the building next to it and added around 245,000 square feet and called it MTC North. We are pleased to announce this week that we now have access to a new building, MTC East, which will start welcoming Moderna employees later this year after some maybe investment and renovation to the building. That is another 240,000 square feet.

2020年，我們在其旁邊添加了建築物，增加了約245,000平方英尺，並將其命名為MTC North。本週我們很高興地宣布，我們現在可以使用一座新大樓 MTC East，在對大樓進行一些投資和翻新後，該大樓將於今年晚些時候開始歡迎 Moderna 員工。這又是 240,000 平方英尺。

So we're now having in MTC access to around 650,000 square feet. We now hold the building on this campus, and we can also add more buildings and build them now that we have the entire campus.

因此，我們現在在 MTC 擁有約 650,000 平方英尺的使用權。我們現在擁有這個校園的建築，既然我們擁有了整個校園，我們還可以添加更多的建築並建造它們。

We are deeply committed about building a company that has a strong sense of responsibility. We want Moderna to be a positive force in the world, not only for our medicines, but also by who we are as a company.

我們致力於打造一家具有強烈責任感的公司。我們希望 Moderna 成為世界上的一股積極力量，不僅是為了我們的藥品，而且是為了我們作為一家公司。

We are very committed to belong, inclusion and diversity. We recently published or expanded workforce diversity figures for the first time. Last year, we signed the CEO Action for Diversity & Inclusion pledge. And we have also reiterated our ongoing commitment to increasing diversity in our clinical trials.

我們非常致力於歸屬感、包容性和多樣性。我們最近首次發布或擴大了勞動力多樣性數據。去年，我們簽署了首席執行官多元化和包容性行動承諾。我們還重申了我們對增加臨床試驗多樣性的持續承諾。

We are deeply committed to the environment. We have decided to source our Norwood and Cambridge site with renewable energy and will offset any energy that is not from renewable sources, and we will be working on our target as to when we should be a net-zero carbon company.

我們堅定地致力於保護環境。我們已決定為諾伍德和劍橋工廠提供可再生能源，並將抵消任何非可再生能源的能源，我們將致力於實現何時成為淨零碳公司的目標。

We also encouraging our employees with a positive impact on the communities in which we live and volunteer, from cleaning the Charles River in Cambridge, to feeding the homeless and stem education and much more. You can find a lot of resources online on our website.

我們還鼓勵員工對我們居住和志願服務的社區產生積極影響，從清潔劍橋的查爾斯河，到為無家可歸者提供食物和乾教育等等。您可以在我們的網站上找到大量在線資源。

As I close, I want to convey how thankful we are at Moderna to have a chance to do what we do. Every day, we come to work to make innovative medicine using the first information platform of a biopharmaceutical industry. My colleagues and I work and collaborate to make more medicines to protect or treat people.

在我結束髮言時，我想表達我們在 Moderna 非常感激有機會做我們所做的事情。我們每天都在利用生物製藥行業第一信息平台進行創新藥物的研發。我和我的同事致力於生產更多藥物來保護或治療人們。

I am proud of what the team has done over the last 10 years to get us to this stage. Over the last 14 months, since we started chasing SARS-CoV-2 virus. And in Q1, as we continue to execute relentlessly.

我為團隊在過去 10 年里為讓我們達到這一階段所做的努力感到自豪。自從我們開始追踪 SARS-CoV-2 病毒以來，過去 14 個月裡。在第一季度，我們繼續不懈地執行。

But as I look at the future of Moderna, I believe we have a chance over the next 5, 10, 20 years to transform medicines potentially like no other company has ever changed medicine. This is just the beginning.

但當我展望 Moderna 的未來時，我相信我們有機會在未來 5 年、10 年、20 年裡像其他公司一樣改變藥品。這僅僅是個開始。

Before taking your questions, I would like to remind you that we will be hosting our Annual Science Day in a few weeks on May 27. You are going to work to connect this event as Stephen and his team have some very cool new things to share with you.

在回答您的問題之前，我想提醒您，我們將在幾週後的5 月27 日舉辦年度科學日。您將努力將這一活動聯繫起來，因為斯蒂芬和他的團隊有一些非常酷的新事物要分享與你。

And later at the end of the summer, on September 9, our annual R&D Day for holistic clinical update.

夏末的 9 月 9 日是我們年度全面臨床更新的研發日。

Operator, we'll be happy to take any questions now.

接線員，我們現在很樂意回答任何問題。

(Operator Instructions)

（操作員說明）

Your first response is from the line of Salveen Richter with Goldman Sachs.

您的第一條回復來自高盛的 Salveen Richter。

I have a couple here. So firstly, with regard to, if the U.S. supports the WHO waiver of COVID-19 vaccine IP, what does that mean for Moderna? I mean if you could just walk us through that.

我這裡有一對。首先，如果美國支持世界衛生組織放棄 COVID-19 疫苗知識產權，這對 Moderna 意味著什麼？我的意思是，如果你能引導我們完成這個過程就好了。

Secondly, if you could just discuss contract dynamics for the vaccine in 2022 as you look to address variants and kind of you see them move towards an endemic market.

其次，當您尋求解決變種問題時，如果您可以討論 2022 年疫苗的合同動態，您會發現它們正在走向流行市場。

And third, it's nice to see the PA program move forward. It would be great to kind of understand whether we'll see data from that program this year and what else we might see from the ex COVID pipeline?

第三，很高興看到 PA 計劃取得進展。如果能了解今年我們是否會看到該計劃的數據以及我們可能會從前新冠肺炎管道中看到什麼，那就太好了？

Salveen, it's Stephane. Let me start with your first questions and then turn few questions to Stephen.

薩爾文，我是斯蒂芬。讓我從你的第一個問題開始，然後向斯蒂芬提出幾個問題。

So on the IP, what does it mean? I believe it doesn't change anything for Moderna. As I said, we had said last October that we will not enforce our COVID-19-related patents during the pandemic. And as I said in my remarks, there is no mRNA in manufacturing capacity in the world. This is a new technology. You cannot go hire people who know how to make the mRNA. Those people don't exist.

那麼關於IP，它意味著什麼呢？我相信這不會給 Moderna 帶來任何改變。正如我所說，我們去年 10 月曾表示，在大流行期間我們不會執行與 COVID-19 相關的專利。正如我在發言中所說，世界上不存在mRNA製造能力。這是一項新技術。你不能去僱用知道如何製造 mRNA 的人。那些人不存在。

And then even if all those things were available, whoever who wants to do mRNA vaccines will have to buy the machine, invent the manufacturing process, invest verification processes, analytical processes. And then they will have to go run a clinical trial, get the data, get the product approved and scale the manufacturing. This doesn't happen in 6 or 12 or 18 months. We have been working at these for years.

即使所有這些東西都可用，無論誰想做 mRNA 疫苗，都必須購買機器，發明製造工藝，投資驗證流程和分析流程。然後他們必須進行臨床試驗，獲取數據，獲得產品批准並擴大生產規模。這不會在 6、12 或 18 個月內發生。我們多年來一直致力於這些工作。

And as you know, there are some smaller mRNA companies that are still in the clinic, trying to get the products to a finish line. And so we saw the news last night and I didn't lose a minute of sleep of the news during the night.

如您所知，有一些規模較小的 mRNA 公司仍處於臨床階段，試圖將產品推向終點。所以我們昨晚看到了這個新聞，我整晚都沒有因為這個新聞而失眠。

On 2022 contract, the dynamic is, as I just described it, which is, the market has tremendously changed. Since the pandemic started last year, before clinical data, many countries as you know, didn't want to move, especially because of mRNA being a new technology. They moved first on protein contracts, on adenos contracts. And then the kind of mRNA contracts came later, more just in case. And then the clinical data came along and the speed to get to approval.

對於 2022 年合約，正如我剛才所描述的那樣，市場發生了巨大變化。自去年大流行開始以來，在獲得臨床數據之前，許多國家都不想採取行動，特別是因為 mRNA 是一項新技術。他們首先轉向蛋白質合約，然後轉向腺苷合約。後來又出現了 mRNA 合同，更多的是為了以防萬一。然後臨床數據出現並加快獲得批准的速度。

And so -- and then you have the fact that the proteins are still not authorized anywhere in the West. And then you had the low efficacy of the adenos in over the safety questions around the adenos, manufacturing scale-up issues that adenos companies have had. And the big question that scientists advising governments are which is, can you actually really boost adenos with more adenos products because, by definition, you give again the same virus vector to somebody that we believe over time will get less and less response from it.

所以——然後你就會發現這些蛋白質在西方任何地方仍然沒有得到授權。然後，在圍繞腺苷的安全問題以及腺苷公司遇到的生產規模擴大問題上，腺苷的功效較低。科學家向政府提供建議的一個大問題是，你真的能用更多的腺苷產品真正增強腺苷嗎？因為根據定義，你再次將相同的病毒載體給予某人，我們相信隨著時間的推移，它會得到越來越少的反應。

So as we look at the marketplace, which what governments are doing, and given many governments, I think last year, believe the pandemic will be gone quickly. Trust me, every governments we're talking to believe this is going to stay for a long time. They have got massively educated by the scientists and the clinician, and they believe this virus is not going away. They believe boosting is going to be critical. They believe variant-specific boosting is going to be the right way to do the science. And as you saw from Stephen's presentation, this is what the clinical data are showing as well.

因此，當我們觀察市場時，政府正在做的事情，考慮到許多政府，我認為去年，相信這種流行病會很快消失。相信我，與我們交談的每個政府都相信這種情況將持續很長時間。他們接受了科學家和臨床醫生的大量教育，他們相信這種病毒不會消失。他們認為，提升將是至關重要的。他們相信，針對特定變體的增強將是開展科學研究的正確方法。正如您從斯蒂芬的演講中看到的，這也是臨床數據所顯示的。

And so the dynamic is that current governments that have already contracted us are calling for more, and we're in active discussion with all of them to supply more for '22 and '23, both prime series and specific-variant booster. The beauty about this technology is, we can agree right now in the contracts to give them next year to be able to choose what they want based on the clinical data. And that's an incredible competitive advantage. And this we can do because, as you know, the manufacturing process is the same for -1273 or -1273.351 or -1273.221 or new 1273 dot something is a new variant. And we can change that on a very short notice because it's a same equipment, in the same room, with the same people, with same raw materials.

因此，目前的動態是，已經與我們簽約的現任政府正在要求提供更多，我們正在與他們所有人積極討論，為“22”和“23”提供更多，包括主要係列和特定變體助推器。這項技術的美妙之處在於，我們現在可以在合同中達成一致，讓他們明年能夠根據臨床數據選擇他們想要的技術。這是一個令人難以置信的競爭優勢。我們可以做到這一點，因為如您所知，-1273 或 -1273.351 或 -1273.221 或新的 1273 點的製造過程是相同的，這是一個新的變體。我們可以在很短的時間內改變這一點，因為它是相同的設備，在同一個房間，由相同的人員使用相同的原材料。

And then -- all those governments, which is almost more exciting to me that never called before -- that we called before, but we couldn't supply them because we are in the unfortunate position and we're very sorry. We have no more supply for you in 2021, which, of course, a very difficult discussion to have given the suffering happening around the world.

然後，所有那些以前從未打過電話的政府，對我來說更令人興奮，我們以前打過電話，但我們無法向他們提供服務，因為我們處於不幸的境地，我們非常抱歉。到 2021 年，我們將不再提供給你們，考慮到世界各地正在發生的苦難，這當然是一個非常困難的討論。

But the great news with the investments we've announced to get up to 3 billion next year. We now can have those discussions with those governments. And Corinne and the team are having a lot of discussions with them. So that kind of give you a sense on the dynamics.

但好消息是我們宣布明年的投資將達到 30 億美元。我們現在可以與這些政府進行討論。 Corinne 和團隊正在與他們進行大量討論。這樣你就可以了解動態。

Stephen, on PA?

斯蒂芬，在賓夕法尼亞州嗎？

Sure. Salveen, thanks for the question. So as you know, the program, the Paramount study for propionic acidemia is going to be looking at biomarkers as a part of its dose optimization. And so it's possible that we'll be seeing very early indicators of impact there. But we are going to -- there's no guarantee that the first dose level and the first cohort that we're looking at will be the correct one. And we're going to make sure that we develop a cogent and consistent data set before we bring that forward. It is a dose optimization study, and we will perhaps be looking at multiple dose levels. So while I think it's possible that we would see data this year, it's dependent upon many things that are well beyond our control.

當然。薩爾文，謝謝你的提問。如您所知，派拉蒙丙酸血症研究計劃將研究生物標誌物作為其劑量優化的一部分。因此，我們有可能會看到非常早期的影響指標。但我們無法保證我們正在研究的第一個劑量水平和第一個隊列將是正確的。在提出這一目標之前，我們將確保開發出令人信服且一致的數據集。這是一項劑量優化研究，我們可能會考慮多個劑量水平。因此，雖然我認為今年我們有可能看到數據，但這取決於許多遠遠超出我們控制範圍的事情。

Now you asked a more general question also about our broader portfolio. And if you look at the programs more generally, VEGF, as we mentioned, is a Phase II program that's been enrolling for a while. It's possible we could see data from that. Our PCV and KRAS programs, again, as open-label programs will continue to track those closely as they enroll. And then similar intratumoral programs that we highlighted, many of them are ongoing and producing data. And of course, when we have a complete and cogent data set, we will bring it forward.

現在您還問了一個關於我們更廣泛的投資組合的更普遍的問題。如果你更廣泛地觀察這些項目，正如我們提到的，VEGF 是一個已經註冊了一段時間的 II 期項目。我們有可能從中看到數據。我們的 PCV 和 KRAS 計劃同樣作為開放標籤計劃，將繼續密切跟踪這些人的註冊情況。然後是我們強調的類似的腫瘤內項目，其中許多項目正在進行中並產生數據。當然，當我們擁有完整且有說服力的數據集時，我們會將其提出。

Your next response is from Matthew Harrison with Morgan Stanley.

您的下一個回復來自摩根士丹利的馬修哈里森。

Great. I guess two from me. One, on the sort of next-generation COVID vaccine where you think it might be refrigerator stable. Can you just talk about the regulatory path for that vaccine given that it's not the full spike. Do you think you might have to run an actual efficacy study? Or do you think a neutralization titer study with safety might be enough for that?

偉大的。我猜我有兩個。一是關於下一代新冠疫苗，你認為它可能在冰箱中穩定。鑑於該疫苗還沒有全面普及，您能談談該疫苗的監管路徑嗎？您認為您可能需要進行實際功效研究嗎？或者您認為安全的中和滴度研究可能就足夠了？

And then the second question, Stephen, if I can just follow up on PA. I know in the past, right, one of the struggles has been enrollment. Obviously, it's great to see that you've gotten a patient into the study. Can you just talk about now that you've gotten a patient in what your sort of view is around enrollment and if you think you've gotten through some of those hurdles?

然後是第二個問題，斯蒂芬，我是否可以跟進 PA。我知道過去的困難之一就是入學。顯然，很高興看到您讓一名患者參與這項研究。您現在能談談您對入組患者的看法嗎？您是否認為自己已經克服了其中一些障礙？

Sure. Thank you, Matt, for both questions. So first on -- I believe you're referencing our second-generation vaccine candidate, which is mRNA-1283. It is a shorter construct that we think could have a much longer refer through its stability profile.

當然。謝謝你，馬特，提出兩個問題。首先，我相信您指的是我們的第二代候選疫苗，即 mRNA-1283。這是一個較短的結構，我們認為通過其穩定性配置文件可以有更長的參考。

As we announced previously, we started enrolling in the Phase I in that study. And it's probably a little bit premature to comment on what we think the regulatory path will look like for that until we get some of that initial data and have conversations, obviously, with regulators. But I would highlight that it's possible that -1283 may not go into a full primary series vaccination study. It could impact in the future function as a booster. But again, that's probably too early to say. We will have to wait until we see that data and ultimately, it would be dependent upon conversations with regulators in the future.

正如我們之前宣布的，我們開始參加該研究的第一階段。在我們獲得一些初始數據並與監管機構進行對話之前，現在評論我們認為的監管路徑可能有點為時過早。但我要強調的是，-1283 可能不會進入完整的初級系列疫苗接種研究。它可能會影響未來的助推器功能。但同樣，現在說這個可能還為時過早。我們將不得不等到看到這些數據，最終，這將取決於未來與監管機構的對話。

As it relates to PA enrollment, yes, as you mentioned, we've been working very hard on that over the coming -- over the past years, and we're quite pleased to have enrolled the first participant, the first patient in that study. And the team is working hard to enroll additional patients as quickly as possible. I think time will tell whether we've actually broken through here and addressed any of the issues that we previously had in terms of enrollment. And so hopefully, we'll be able to provide subsequent updates on expanding enrollment in the near term that will demonstrate that we've made that progress.

因為它與 PA 註冊有關，是的，正如您提到的，在過去的幾年裡，我們一直在努力工作，我們很高興註冊了第一個參與者，第一個患者。學習。該團隊正在努力盡快招募更多患者。我認為時間會證明我們是否真正突破了這一點並解決了我們之前在招生方面遇到的任何問題。因此，希望我們能夠在短期內提供有關擴大招生的後續更新，以證明我們已經取得了進展。

Your next response is from Ted Tenthoff with Piper Sandler.

您的下一個回復來自 Ted Tenthoff 和 Piper Sandler。

Great. Thank you for all of the detailed updates. including running through the financial analysis. So detailed, David. Congrats on all the success. Stephen, I wanted to pick up on the booster data that you've shown. And maybe you can kind of take us a step forward. What is the booster strategy going to look like. Do We actually need to maybe do redose or revaccinate sooner than 8 to 6 months because of where the levels were? And maybe you can just tell us what you see as sort of the potential timing in queue for when we would be getting boosters.

偉大的。感謝您提供所有詳細更新。包括進行財務分析。這麼詳細，大衛。祝賀一切成功。斯蒂芬，我想了解一下你所展示的助推器數據。也許你可以帶領我們向前邁出一步。助推器策略會是什麼樣子？由於水平的原因，我們是否真的需要在 8 至 6 個月內重新註射或重新接種疫苗？也許您可以告訴我們您認為我們獲得助推器的潛在時間。

Thank you for the question, Ted. Look, I think we have to start by saying we don't know. We do not have data on when to expect waning immunity leading to breakthrough infections. But we do know that there is a raging pandemic that reinfections will happen at some point. And the best way to ensure that we do not have renewed outbreaks in well vaccinated countries is to boost and maintain the highest possible levels of neutralizing immunity.

謝謝你的提問，特德。聽著，我想我們必須首先說我們不知道。我們沒有關於何時預計免疫力減弱會導致突破性感染的數據。但我們確實知道，大流行正在肆虐，在某個時候會發生再次感染。確保疫苗接種良好的國家不會再次爆發疫情的最佳方法是增強和維持盡可能高水平的中和免疫力。

We, as Moderna, also believe that, that means we want to maintain the broadest neutralizing immunity against the largest number of than circulating variants of concern.

我們，作為 Moderna，也相信，這意味著我們希望保持最廣泛的中和免疫力，對抗最多數量的流行變種。

If you look at the data that we have posted today as well as some of our published data and others reports, it does feel like immunity to a primary vaccination series or a previous infection seems to weigh in over the 6- to 12-month time horizon, at least as measured by neutralizing titers. Again, we don't know whether that's a clinical cohort or not, but it certainly is an indication of that waning immunity.

如果您查看我們今天發布的數據以及我們發布的一些數據和其他報告，您會發現，對初級疫苗系列的免疫力或之前的感染似乎在 6 至 12 個月的時間內發揮了重要作用地平線，至少通過中和滴度來測量。同樣，我們不知道這是否是一個臨床隊列，但這確實表明免疫力正在減弱。

And if you look at the data that we -- that I presented earlier, approximately half of the participants in our booster studies, no longer have detectable neutralizing immunity against the variants of concern. They have neutralizing immunity against the ancestral strain that they were vaccinated against.

如果你看一下我之前提供的數據，我們的加強研究中大約一半的參與者不再具有可檢測到的針對所關注變異的中和免疫力。他們對所接種疫苗的祖先菌株具有中和免疫力。

So the logical thing we think to do is to boost their immunity against those variants of concern. If you will vaccinate them against those to both increase those titers right now, but also give them a longer duration of protection, perhaps long enough, that we can see our way through the pandemic. That probably looks like boosting on a 9 to 12 months after primary series as an annual booster for now. At least while we're continuing to see the evolution of the virus.

因此，我們認為要做的合乎邏輯的事情是增強他們對這些令人擔憂的變體的免疫力。如果你給他們接種疫苗，既可以立即增加這些病毒的滴度，又可以給他們更長的保護時間，也許足夠長，這樣我們就可以找到度過這場大流行的方法。目前看來，這可能像是初選系列賽后 9 到 12 個月的年度助推器。至少在我們繼續觀察病毒的進化過程中是這樣。

Now the last point was about our strategy more generally here. And we do believe that the virus is not going to follow one path of evolution. That we are going to see many variants of concern, that there may be divergent paths. And therefore, the best way to ensure that we can protect against the broadest number of variants of concern will be a multivalent vaccine.

最後一點是關於我們這裡更一般的策略。我們確實相信該病毒不會遵循一種進化路徑。我們將看到許多令人擔憂的變體，可能存在不同的路徑。因此，確保我們能夠預防最廣泛的受關注變種的最佳方法是多價疫苗。

Now right now, we're still waiting to see our multivalent vaccine data, which is a combination, as you know, of ancestral and 351, the strain first identified in South Africa. But we think this is just the beginning, and we think we're going to be unfortunately continuing to fight this pandemic through 2022, at least, globally. And therefore, we're committed as a company to make as many updates to the vaccine, to add as many variants as we think are necessary, to ensure that when people receive a booster, it provides the broadest immune protection against the widest range of variants.

現在，我們仍在等待查看我們的多價疫苗數據，如您所知，這是祖傳病毒株和 351 毒株（南非首次發現的毒株）的組合。但我們認為這只是一個開始，我們認為不幸的是，至少在全球範圍內，我們將在 2022 年之前繼續抗擊這一流行病。因此，作為一家公司，我們致力於對疫苗進行盡可能多的更新，添加我們認為必要的盡可能多的變體，以確保當人們接受加強疫苗時，它能針對最廣泛的範圍提供最廣泛的免疫保護。變種。

Your next response is from Michael Yee with Jefferies.

您的下一個回復來自 Jefferies 的 Michael Yee。

I appreciate the questions. I had two important follow-ups. One was going back to the question about the WTO. Can you just offer some color around the view of loss of raw material supply capacity, et cetera? In other words, shedding some light on any ability to actually increase global capacity even if there were some form of open patents. So maybe just talk about that. Because I don't think that you can just make it. And like it's easy. Can you maybe just offer some color there?

我很欣賞這些問題。我有兩個重要的後續行動。一是回到關於世貿組織的問題。您能否就原材料供應能力喪失等問題提供一些看法？換句話說，即使存在某種形式的開放專利，也揭示了實際增加全球產能的任何能力。所以也許只是談談這個。因為我不認為你能做到。好像這很容易。你能提供一些顏色嗎？

And the second question is also a follow-up on the variant strategy. It sounds like the bivalent strategy might be the best, Stephen. So at what point would you just pull the trigger on beginning to manufacture that and ramp that all up for 2022?

第二個問題也是變體策略的後續。聽起來二價策略可能是最好的，斯蒂芬。那麼，您會在什麼時候開始生產該產品，並在 2022 年全力以赴？

Thanks, Michael. It's Stephane. Let me start on the raw material. Going back to what I said is, if somebody was to start from scratch because again there is no mRNA player that's with idle capacity out there. One will not start by focusing on large-scale raw material supply. I mean why will I first figure out how do we make mRNA. And you cannot find that patent, which as you all know are on the founded on the U.S., but they block this website. And so one is going to figure out what machine do you need, how do you make mRNA, what purification method you need, what analytical methods you need. And once you recognize all those things, which trust me is going to take you time, it is not easy. Us and other companies that are in the market we are on a vaccine that we've been building for decades. And even companies that have been working on it for 10 or 20 years are still in a clinic trying to figure out how to get to the finish line.

謝謝，邁克爾。這是斯蒂芬。讓我從原材料開始。回到我所說的，如果有人要從頭開始，因為同樣不存在閒置產能的 mRNA 播放器。我們不會從關注大規模原材料供應開始。我的意思是為什麼我要首先弄清楚我們如何製造 mRNA。你找不到該專利，眾所周知，該專利是在美國創建的，但他們屏蔽了該網站。所以我們要弄清楚你需要什麼機器，你如何製造 mRNA，你需要什麼純化方法，你需要什麼分析方法。一旦你認識到所有這些事情，相信我會花費你時間，這並不容易。我們和市場上的其他公司正在使用我們幾十年來一直在研發的疫苗。即使是已經為此研究了 10 年或 20 年的公司仍處於臨床階段，試圖弄清楚如何到達終點線。

And so I really believe that this is not the issue. I already believe the IP topic is mostly critically driven. It is not the issue. It might impact other technology that had a role in proteins and this I could not comment on. But for mRNA, I really think this is the wrong question. Stephen, do you want to take the variants?

所以我真的相信這不是問題。我已經相信知識產權主題主要是由批判性驅動的。這不是問題所在。它可能會影響其他在蛋白質中發揮作用的技術，對此我無法發表評論。但對於 mRNA，我真的認為這是一個錯誤的問題。斯蒂芬，你想採用變體嗎？

Yes. So thank you, again, Michael, for the question. So on our multivalent strategy, we have -- at this point, we are still waiting for the clinical data to confirm that. And as we expect to have that shortly, as we've mentioned, we previously dosed people with the mRNA-1273.211 variant. The preclinical data that we have published does -- or presented to dose suggest that, that is going to be the winning approach. And as I highlighted, or as is highlighted by the monovalent clinical data we already have, there is a benefit to adding additional antigens and potentially, therefore, benefit with a multivalent approach.

是的。再次感謝邁克爾提出的問題。因此，在我們的多價策略上，我們目前仍在等待臨床數據來證實這一點。正如我們所提到的，我們預計很快就會實現這一點，我們之前給人們注射了 mRNA-1273.211 變體。我們已經發布的臨床前數據確實——或者提供的劑量表明，這將是獲勝的方法。正如我所強調的，或者正如我們已有的單價臨床數據所強調的，添加額外的抗原是有好處的，因此，多價方法可能會受益。

I think it's important to recognize that we view this as an ongoing battle. And so your question about when do we pull the trigger and move forward bivalent manufacturing. We're already on the path of doing that manufacturing, not because we think that we're done with mRNA-1273.211 the bivalent -- current bivalent vaccine, but because we think we're going to go down the path of multivalent vaccines and continue needing to add things.

我認為重要的是要認識到我們認為這是一場持續的戰鬥。所以你的問題是我們什麼時候扣動扳機並推進二價製造。我們已經走上了生產之路，不是因為我們認為我們已經完成了二價疫苗 mRNA-1273.211 的開發，而是因為我們認為我們將走上多價疫苗的道路，繼續需要添加東西。

And so that platform capability, we are already in the process of building and establishing to support multiple updates to a multivalent vaccine.

因此，我們已經在構建和建立平台能力，以支持多價疫苗的多次更新。

And we do think that's going to be required because we think the virus is not going to stand still and stop evolving, and we suspect there's going to be trivalent, maybe quadrivalent. It will keep happening in the time ahead. We have completed GMP manufacturing of all of those batches, and we're at sufficient scale, we think, to be able to quickly move into commercial scale distribution if needed. But at this point, we are still waiting for data to come shortly to confirm that performance in clinic.

我們確實認為這是必要的，因為我們認為病毒不會停滯不前並停止進化，我們懷疑將會是三價，也許是四價。這種情況在未來還會繼續發生。我們已經完成了所有這些批次的 GMP 生產，並且我們認為，我們的規模足夠大，能夠在需要時快速進入商業規模分銷。但目前，我們仍在等待不久後的數據來確認臨床表現。

Yes. So just a point to add to Stephen on a multivalent, which I think a lot of people don't appreciate is, it is not easy to do a multivalent mRNA, GMP product from an analytical QC standpoint because those mRNAs are of the same size. They look mostly similar because you just changed a few -- I mean a few nucleic acid. And that expand now. And it's why the platform comes to drive so much value. As you all know, we have a CMV vaccine on its way to Phase III, where we developed and that we find over the years, a very complex product, seeks mRNA in the same guidance.

是的。因此，我想在多價方面向 Stephen 補充一點，我認為很多人不理解的是，從分析 QC 的角度來看，製作多價 mRNA、GMP 產品並不容易，因為這些 mRNA 的大小相同。它們看起來大多相似，因為你只是改變了一些——我的意思是一些核酸。現在這種情況正在擴大。這就是該平台能夠帶來如此大價值的原因。眾所周知，我們的 CMV 疫苗即將進入 III 期，我們在該階段開發了這種疫苗，多年來我們發現這是一種非常複雜的產品，在相同的指導下尋求 mRNA。

So if you think about what the multivalent vaccine for COVID is going to look like, it's not going to be easy. And so for people that have not done multivalent in GMP setting before, trust me, the regulators because we had this discussion with regulators around CMV over years. They didn't want to see a lot of analytical method characterization so that you can prove to them that you know what is in the pipe. And that is yet again another big differentiation with Moderna.

因此，如果你想到新冠肺炎多價疫苗會是什麼樣子，就會發現這並不容易。因此，對於以前沒有在 GMP 環境中進行過多價處理的人來說，相信我，監管機構，因為多年來我們與監管機構圍繞 CMV 進行了討論。他們不想看到大量的分析方法表徵，以便您可以向他們證明您知道管道中的內容。這又是 Moderna 的另一個重大區別。

Your next response is from Gena Wang of Barclays.

您的下一個回復來自巴克萊銀行的 Gena Wang。

I also have two. One also related to the IP question. So wanted to ask differently, just wondering, Stephane, how many contracted global manufacturing sites you have? And how long in general is the contract?

我也有兩個。其中之一也與知識產權問題有關。所以想問不同的問題，只是想知道，Stephane，你們有多少個簽約的全球製造基地？合同期限一般是多長？

And the second question also regarding the new booster data. This is more for Steve, actually, to me, it was a little bit surprised the differences between -1273 versus -1273.351 was less or narrow than initially I would expect it. It seems like -1273 should be also sufficient to protect from variant strain. So what could be the explanation? And then you did just lay out the plan, you still will be going after the multi-variant approach. But regarding the explanation there, like do you think that, that just a single shot that was should be sufficient for the protection?

第二個問題也與新的助推器數據有關。這對史蒂夫來說更重要，實際上，對我來說，-1273 與 -1273.351 之間的差異比我最初預期的要小或窄，這讓我有點驚訝。看起來 -1273 也應該足以防止變異菌株。那麼可以解釋什麼呢？然後你剛剛制定了計劃，你仍然會追求多變體方法。但對於那裡的解釋，你是否認為，只要一擊就足以保護？

Thanks, Gena. I'll -- maybe I'll take that question first and then hand it back to Stephane on your IP question. So a couple of things I would note. The first is the level of titers, as you suggested, there's a little bit less than twofold difference between them, and you are -- when you are seeing substantially higher titers in the order of 1,400 when you give the very specific booster, that's mRNA-1273.351.

謝謝，吉娜。我會——也許我會先回答這個問題，然後將您的知識產權問題交給斯蒂芬。所以我要注意一些事情。第一個是滴度水平，正如您所建議的，它們之間的差異略小於兩倍，當您給予非常具體的加強劑（即 mRNA）時，您會發現滴度明顯更高，約為 1,400 -1273.351。

Now I would note that this is happening already at Day 15, right? This is an early time point that we're looking at, at this point. We will also be looking at Day 29. And in this case, we are -- effectively, it is a prime with the 1273.351, right? It is the first dose of the strain first identified in South Africa. And so it's actually -- there's 2 ways you could look at it. One is obviously that it is -- both look good. I think the other and the way that I'm still looking at this is, it looks like we can very rapidly direct the immune response to an increased level of neutralizing titers against the variant of concern that was first identified in South Africa 351 in this case.

現在我要指出的是，這已經在第 15 天發生了，對嗎？這是我們目前正在研究的早期時間點。我們還將關注第 29 天。在這種情況下，我們實際上是 1273.351 的質數，對吧？這是在南非首次發現的該菌株的第一劑。事實上，你可以通過兩種方式來看待它。其一顯然是——兩者看起來都不錯。我認為另一個也是我仍在研究的方式是，看起來我們可以非常迅速地引導免疫反應，以提高針對南非首次發現的關注變體的中和滴度水平351案件。

And if you compare the titers that we've achieved even by day 15, between these 2 variants -- or between the ancestral strain and the 351 strain, it's really only the 351 strain that's getting to the same level that we saw against the ancestral strains in that last comparison. So to levels that are approximately similar amount.

如果你比較我們在第 15 天時所達到的滴度，在這 2 個變體之間，或者在祖先菌株和 351 菌株之間，實際上只有 351 菌株達到了我們與祖先菌株相同的水平。最後一個比較中的壓力。所以達到大約相似數量的水平。

Now that's not to say that mRNA-1273 as a booster couldn't -- wouldn't provide a benefit, and I think you're highlighting that, Gena. There is evidence in this data as well that we can substantially increase neutralizing titers generally across the response with a booster dose of mRNA-1273, our authorized vaccine at 50 micrograms. And that is encouraging. That is good news because I think it suggests that is also a useful strategy. But if you had to choose between the 2, and you were primarily concerned about increasing immunity to a higher level so that it can last longer, particularly in patient populations at high risk of either waning immunity or incomplete immunity, we think this starts to provide very early event, even at Day 15, even after a priming dose, that there's going to be an advantage to some strain matching of the antigen. And that's what has us continue to be excited about a multivalent strategy. Stephane?

這並不是說 mRNA-1273 作為增強劑不能——不會提供益處，我認為你強調了這一點，Gena。該數據也有證據表明，我們可以通過加強劑量的 mRNA-1273（我們授權的疫苗，劑量為 50 微克）顯著提高整個反應過程中的中和滴度。這是令人鼓舞的。這是個好消息，因為我認為這表明這也是一個有用的策略。但是，如果您必須在兩者之間進行選擇，並且您主要擔心將免疫力提高到更高水平，以便持續更長時間，特別是在免疫力減弱或免疫力不完全的高風險患者群體中，我們認為這開始提供非常早的事件，即使在第 15 天，甚至在引髮劑量之後，抗原的某些菌株匹配也會有優勢。這就是我們繼續對多價戰略感到興奮的原因。斯蒂芬？

Sure. Thanks, Stephen. So Gena, on the contract manufacturers, we kind of look at kind of raw material drug substance and drug products. In all of these, we have multiyear contracts. As soon as we got board's authorization to go to 3 billion supply for 2022, we right away, sent a lot of orders and a lot of additional supplies to our suppliers. And not to forget the drug substance actually now, it is the place, it's on Moderna site where we actually have the biggest capacity of a drug substance even in the 3 billion dose 2022 scenario over.

當然。謝謝，斯蒂芬。所以 Gena，在合同製造商方面，我們關注的是原料藥和藥品的種類。在所有這些方面，我們都有多年合同。當我們獲得董事會授權在 2022 年供應 30 億美元時，我們立即向我們的供應商發送了大量訂單和大量額外供應。現在不要忘記實際上的原料藥，就在 Moderna 網站上，我們實際上擁有最大的原料藥容量，即使在 2022 年 30 億劑量的情況下也是如此。

Your next response is from Geoff Meacham with Bank of America.

您的下一個回復來自美國銀行的 Geoff Meacham。

Just had two on COVID. The first one is, what does your data tell you with real-world effectiveness of -1273 today as of now with respect to some of the main variants? I'm just trying to reconcile the need for annual boosters versus minimal breakthroughs thus far and high efficacy.

剛剛有兩個關於新冠病毒的事情。第一個是，截至目前 -1273 的實際有效性，您的數據告訴您一些主要變體的什麼信息？我只是試圖協調每年加強劑的需求與迄今為止的最小突破和高功效之間的關係。

And then the second question is, when the next-gen vaccines for COVID-19, when you have some permutations, what's the potential to leverage the technology to use different parts of the virus versus just modifying the spike protein or do you think this could add regulatory steps that make it difficult, even if it's theoretically possible.

第二個問題是，當下一代COVID-19 疫苗出現時，當你有一些排列時，利用該技術使用病毒的不同部分與僅僅修改刺突蛋白相比，有什麼潛力，或者你認為這可以嗎？增加監管措施，使其變得困難，即使理論上是可能的。

Thank you, Geoff. Those are both good questions. So maybe I'll take the first one, first, which is our real-world evidence, the largest amount of it that we've seen has been published by groups like the CDC and continues to reinforce that the efficacy we saw in the clinical trial seems to be translating well into real-world use with very high efficacy against disease, against COVID-19.

謝謝你，傑夫。這些都是好問題。所以也許我會採取第一個，首先，這是我們現實世界的證據，我們所看到的最大數量的證據已經由疾病預防控制中心等組織發表，並繼續強化我們在臨床中看到的功效試驗似乎很好地轉化為現實世界的使用，對疾病、COVID-19 具有非常高的功效。

I think it's important to note, though, that this is all happening very acutely, right? We're still only months away into -- we're months into these vaccination campaigns. And the primary concern that we and others have from a public health perspective is really not what's going to happen right after vaccination. But what does this look like in 9 months? What does this look like in 18 months? And I think that the really difficult situation everybody is in is you could say, well, let's wait until it's a year from now, and we see a reemergence of spikes of cases. We see -- maybe it's not as bad, but we see a very big and bad flu season in the winters, tens of thousands, maybe hundreds of thousands of death, that kind of scale. That's not a situation that most are willing to take a risk on because it obviously could be substantially worse than that.

不過，我認為值得注意的是，這一切都發生得非常突然，對吧？距離疫苗接種活動的開展還有幾個月的時間。從公共衛生的角度來看，我們和其他人最關心的並不是接種疫苗後會發生什麼。但 9 個月後會是什麼樣子呢？ 18 個月後會是什麼樣子？我認為每個人都面臨的真正困難的情況是你可以說，好吧，讓我們等到一年後，我們會看到病例再次出現激增。我們看到——也許情況沒有那麼糟糕，但我們看到冬天有一個非常大和嚴重的流感季節，數万人、也許數十萬人死亡，這種規模。大多數人都不願意冒險面對這種情況，因為情況顯然可能比這更糟糕。

And so we're probably not going to have a chance to wait for data for cases to really break through a year from after vaccination in the real-world setting and let that start to guide revaccination decisions.

因此，我們可能沒有機會等待在現實世界中接種疫苗後一年後病例數據真正突破，並讓其開始指導重新接種疫苗的決定。

At that point, it's almost too late. And so I think at this level, we think for the very near term, the correct and sort of conservative decision is to continue to try and maintain the highest level of broadest immunity in the populations that are well vaccinated already.

到那時，幾乎為時已晚。因此，我認為在這個層面上，我們認為在短期內，正確且保守的決定是繼續努力在已經接種疫苗的人群中維持最高水平的最廣泛的免疫力。

Now if you look beyond this sort of epidemic phase or pandemic phase that we're in with this variant evolution, into the years beyond that, so 3, 4, 5 years from now, hopefully, we're well past the current pandemic. We still believe there's going to be SARS-CoV-2 reinfections. And as we shared at the Vaccines Day just a couple of weeks ago, we take that lesson from the previous endemic coronavirus epidemics that have happened, where hundreds of years later, you still see reinfections, mortality, substantial health care costs associated with those viruses. And we don't know whether SARS-CoV-2 is worse than them or the same, but we believe that, that burden of disease that's created by the fact that respiratory viruses continually reinfect. And when they do, they can really have a devastating effect in high-risk populations, particularly older immunocompromised. We think that's a real probability in the future. In fact, it would almost be unprecedented for that not to be the case in the coronavirus context.

現在，如果你超越我們所處的這種變異進化的流行病階段或大流行病階段，再看看之後的幾年，那麼從現在起3、4、5年後，希望我們能夠遠遠地度過當前的大流行病。我們仍然相信 SARS-CoV-2 將會再次感染。正如我們幾週前在疫苗日上分享的那樣，我們從以前發生的地方性冠狀病毒流行中吸取了教訓，數百年後，您仍然會看到與這些病毒相關的再感染、死亡和巨額醫療費用。我們不知道 SARS-CoV-2 是否比它們更嚴重或相同，但我們相信，呼吸道病毒不斷重新感染所造成的疾病負擔。當它們這樣做時，它們確實會對高危人群，特別是免疫功能低下的老年人產生毀滅性影響。我們認為這在未來確實有可能發生。事實上，在冠狀病毒背景下，如果不是這種情況，那幾乎是史無前例的。

And so for that reason, we believe there is going to be a need for continual boosters, whether it's annual or not and whether the multivalency continues to add more and valencies, I don't think anybody can say yet. But it's certainly a situation we're preparing for.

因此，出於這個原因，我們相信將需要持續的助推器，無論是否每年一次，以及多價是否繼續增加更多和價，我認為還沒有人能說。但這肯定是我們正在準備的情況。

And Stephane, just on the second question on the different modalities or Stephen, either...

斯蒂芬，就關於不同模式的第二個問題，或者斯蒂芬，要么......

Yes, Geoff, sorry. I apologize for that. And this is your second question on different modalities and different parts of the antigen. So I think what is pretty clear from all the vaccines, if you look across them, but certainly if you focus on the messenger RNA vaccines is that the high degree of efficacy we're seeing in vaccines right now is based on spike protein immunogenicity. That is the antigen that's being expressed.

是的，傑夫，抱歉。我對此表示歉意。這是關於抗原的不同方式和不同部分的第二個問題。因此，我認為，如果你仔細觀察所有疫苗，但如果你關注信使 RNA 疫苗，那麼可以肯定的是，我們現在在疫苗中看到的高度功效是基於刺突蛋白免疫原性。這就是正在表達的抗原。

Is it theoretically possible that non-spike antigens could have provided the same protection? I think it's definitely possible. So forward-looking possible. But I think you would be remiss to look past the multiple large Phase III trials that provide pretty conclusive evidence of the value of going up for spike protein and trying to prevent COVID-19.

理論上，非刺突抗原是否可以提供相同的保護？我認為這絕對是可能的。所以前瞻性是可能的。但我認為，如果你忽略多項大型 III 期試驗，那就太失職了，這些試驗提供了相當確鑿的證據，證明了增加刺突蛋白並試圖預防 COVID-19 的價值。

So I think you would probably -- if you went down that route have to redemonstrate that efficacy that may be increasingly difficult in a world where we have so many good choices in terms of vaccines. And so I'm not exactly sure how we go down that path, even theoretically.

因此，我認為，如果您沿著這條路走下去，您可能必須重新證明這種功效，而在我們在疫苗方面有如此多好的選擇的世界中，這可能會變得越來越困難。因此，即使在理論上，我也不確定我們如何走這條路。

Your next response is from Cory Kasimov with JPMorgan.

您的下一個回復來自摩根大通的科里·卡西莫夫 (Cory Kasimov)。

I want to go back to the topic of the future contracts. I know this has kind of been asked in a couple of different ways, but on discussions and negotiations that are currently taking place, how much confidence do you have that there's going to be demand to fill up to 3 billion doses in anticipated supply that you think you could have next year, especially if people are getting a single annual booster in the future?

我想回到未來合同的話題。我知道有人以幾種不同的方式提出了這個問題，但是根據目前正在進行的討論和談判，您對預計供應量中將有多達 30 億劑疫苗的需求有多大信心？你認為你明年可能會得到，特別是如果人們將來每年都會得到一次加強劑的話？

And then the second question is from really a modeling perspective. Are the price points currently being negotiated on future contracts comparable to what you have on the existing ones for 2021? Just basically wanted to see if we should be assuming stable pricing for modeling purposes for '22.

第二個問題是從建模的角度來看的。目前正在協商的未來合同價格是否與 2021 年現有合同價格相當？基本上只是想看看我們是否應該假設 22 年的建模目的是穩定的定價。

Yes. So let me take a stab at the question, Cory. And if I miss anything, Corinne, just please add some color. So as I said in my remarks, from what we're hearing from customers, this is becoming an mRNA market looking forward. And so there are not so many players in the mRNA market. And if you look at what the future needs across the globe, you're going to see have vaccinate others. All others are not going to get vaccinated this year on the planet. The math doesn't work.

是的。所以讓我來回答一下這個問題，科里。如果我錯過了什麼，科琳，請添加一些顏色。正如我在發言中所說，從我們從客戶那裡聽到的情況來看，這正在成為一個令人期待的 mRNA 市場。因此 mRNA 市場上的參與者並不多。如果你看看全球未來的需求，你會發現已經為其他人接種了疫苗。今年地球上所有其他人都不會接種疫苗。數學不行。

And then you have adolescents and then you have children across the world. And then you are boosting. So when you add all those pieces, the reason we are building up to 3 billion of supply as a mix between the prime series and boosters is because we believe that this is what the world is looking for based on the daily engagements we have with governments around the world. It's a very different setup than what it was a year ago.

然後世界各地都有青少年和兒童。然後你就在提升。因此，當你添加所有這些部分時，我們之所以將主要係列和助推器混合在一起提供高達30 億的供應量，是因為我們相信，根據我們與政府的日常接觸，這就是世界正在尋找的東西世界各地。與一年前相比，這是一個非常不同的設置。

A year ago, you get people saying, "Oh, I'm going to get cheap adenovirus vaccine because it means supplied at cost." This is not a discussion anymore today. The discussion is, "I want some mRNA vaccine for my people, I want variant booster specific, I want multi-variant, I want the best thing because I don't want a second and the third and the fourth year with this thing. I need my country to be back on its feet." Did that help, Cory?

一年前，人們會說：“哦，我要獲得廉價的腺病毒疫苗，因為這意味著按成本價供應。”今天不再討論這個問題。討論是，“我想要為我的人民提供一些mRNA 疫苗，我想要特定的變種加強疫苗，我想要多變種，我想要最好的東西，因為我不想在第二年、第三年和第四年使用這個東西。我需要我的國家重新站起來。”這有幫助嗎，科里？

Yes. No, on the pricing question for modeling.

是的。不，關於建模的定價問題。

No. Look, I think, I'll give you any color, but again, there is no more discussion at all, that your price is this and there's a small company. That company will price at cost at $3, this discussion is gone.

不，聽著，我想，我會給你任何顏色，但同樣，根本沒有更多的討論，你的價格是這樣的，而且有一家小公司。那家公司將按成本定價 3 美元，這個討論就沒有了。

Your next response is from Hartaj Singh with Oppenheimer & Company.

您的下一個回復來自 Oppenheimer & Company 的 Hartaj Singh。

Great. A question I would have is just on the 50-microgram going forward, the booster and against variants. Would you see that potentially becoming your initial kind of prime boost vaccine possibly in the future? Or you think you'll stick with the 100-microgram route, whether it's with 1283 also.

偉大的。我想問的一個問題是關於 50 微克的未來、增強劑和對抗變體。您認為它將來可能成為您最初的增強疫苗嗎？或者您認為您會堅持使用 100 微克路線，無論是否也使用 1283。

And then just on OpEx, just any kind of color when we think about '22 and '23 for David, what cost of goods sold could look like once these quarterly variations kind of flush out? And then what your adjusted operating margins could start looking like us?

然後就運營支出而言，當我們考慮大衛的“22”和“23”時，任何一種顏色，一旦這些季度變化消失，銷售商品的成本會是什麼樣子？那麼你們調整後的營業利潤率可能會開始像我們一樣呢？

Thanks, Hartaj. I'll take a stab at the first one and then hand to David for the other. So on 50 micrograms, obviously, the data we shared today is a small number of subjects. But we've previously shared and published our Phase II data on a slightly larger number of subjects looking at a 50-microgram primary series. That looked quite good and at least as measured by immunogenicity seemed to achieve levels that were consistent with 100-microgram dose.

謝謝，哈塔傑。我會嘗試第一個，然後將另一個交給大衛。那麼就50微克而言，顯然我們今天分享的數據只是少數科目。但我們之前已經分享並發布了有關 50 微克初級系列的更多受試者的 II 期數據。這看起來相當不錯，至少從免疫原性測量來看，似乎達到了與 100 微克劑量一致的水平。

So it's certainly something we're going to look at as to whether or not we could pursue a 50-microgram primary series. But how we get there will depend upon data that we don't yet have, right? So we will have to look at whether there are clear correlates of protection that we can use to bridge between those doses and/or we'll have to look at different populations in which we started those doses. As an example, this has been shared. We're evaluating 50 micrograms as a potential primary series even in pediatric populations. As you can imagine, you don't need perhaps as higher dose in younger people than you do in older ones.

因此，我們肯定會考慮是否可以追求 50 微克的初級系列。但我們如何實現這一目標將取決於我們尚未掌握的數據，對嗎？因此，我們必須研究是否存在明顯的保護相關性，可以用來在這些劑量之間建立橋樑，和/或我們必須研究開始使用這些劑量的不同人群。例如，這已被共享。我們正在評估 50 微克作為潛在的主要係列，甚至在兒科人群中也是如此。正如您可以想像的那樣，年輕人可能不需要比老年人更高的劑量。

So there's a lot of things ahead of us in terms of looking at whether or not a primary series for 50 micrograms is possible. Certainly for a booster series, that is the top dose at which we're looking. And as we look forward, we'll continue to carefully evaluate whether or not we can adopt that as a target dose across all of our applications. But it will depend on data.

因此，在研究 50 微克的初級系列是否可行方面，我們還有很多事情要做。當然，對於加強系列來說，這是我們正在尋找的最高劑量。展望未來，我們將繼續仔細評估是否可以將其作為我們所有應用的目標劑量。但這將取決於數據。

Great. And then question on the...

偉大的。然後問關於...

No. Go ahead, David.

不，繼續吧，大衛。

Yes. So cost of goods and operating expense trends as in '22 and beyond. I guess what I'd say is it's a little early to start giving that kind of guidance for 2022. What I would say is that, if you look at our cost of goods and the cost of goods manufacturing thus far, we've been quite pleased with what we're seeing as we've ramped up production initially here in the U.S. We've seen, as I said, yields have been better than we'd foreseen as we did the initial planning. So that's obviously very helpful.

是的。因此，商品成本和運營費用的趨勢與 2020 年及以後相同。我想我想說的是，現在開始為 2022 年提供此類指導還為時過早。我想說的是，如果你看看我們迄今為止的商品成本和商品製造成本，我們一直在我們對所看到的情況非常滿意，因為我們最初在美國提高了產量。正如我所說，我們看到，產量比我們最初計劃時預期的要好。這顯然非常有幫助。

And we reiterated today We think right now, the right planning assumption continues to be 20% cost of goods. As you move beyond '21, you get into a question of vaccines versus therapeutics. We think cost of goods manufactured will be very competitive for this product. And therefore, margins and gross margins will depend very much on price levels, which I think it's early to comment on.

今天我們重申，我們認為目前正確的規劃假設仍然是 20% 的商品成本。當你跨過 21 世紀，你就會陷入疫苗與治療的問題。我們認為該產品的製造成本將非常有競爭力。因此，利潤率和毛利率將在很大程度上取決於價格水平，我認為現在對此發表評論還為時過早。

And then in terms of operating expenses, we are building out the company. We continue to do that. And as I mentioned, we -- while our overall operating expenses were quite stable at $0.5 billion in the first quarter. We do see that trending up as we now move through the year. And we'll continue to invest appropriately to drive the portfolio investment and to build out globally. So I would say we'll continue to do that. And we'll give you better and more precise guidance here as we move closer to '22 and beyond.

然後在運營費用方面，我們正在擴建公司。我們將繼續這樣做。正如我所提到的，我們第一季度的整體運營支出非常穩定，為 5 億美元。隨著今年的進展，我們確實看到了這種趨勢。我們將繼續進行適當的投資，以推動組合投資並在全球範圍內進行擴張。所以我想說我們會繼續這樣做。隨著 22 世紀及以後的臨近，我們將在這里為您提供更好、更準確的指導。

Your next response is from Joseph Stringer with Needham & Company.

您的下一個回復來自 Needham & Company 的 Joseph Stringer。

Just another one on manufacturing capacity there. As you potentially move to next-generation COVID vaccines. Just wondering if you could give us a sense, maybe even qualitatively in terms of the -- given the modularity of the technology, what a potential manufacturing ramp would look like for some of the second-gen vaccines in terms of manufacturing capacity and the ramp relative to what we had seen with -1273.

這只是關於那裡的製造能力的另一件事。當您有可能轉向下一代新冠疫苗時。只是想知道您能否給我們一種感覺，甚至可能是定性的——考慮到技術的模塊化，一些第二代疫苗的潛在生產量在生產能力和生產量方面會是什麼樣子？相對於我們在-1273 中看到的情況。

Yes. It's Stephane. So the -1273 ramp has been constrained by manufacturing capacity. So if you look at this year, the only -- we "only supply 100 million" to those in Q1, which is an extraordinary number is because we are building the capacity. And so the way to think about it is, as Corinne and her team are working out to add new lines and to increase the capacity, the ramps of follow-on products will be much faster because today, manufacturing is slowing down the ramp. So I anticipate that as you think about the multivalent booster launches, as you think about RSV to CMV launch, we will not be on the back foot.

是的。這是斯蒂芬。因此-1273的坡道一直受到製造能力的限制。因此，如果你看看今年，唯一的——我們“只向第一季度供應了 1 億”，這是一個非同尋常的數字，因為我們正在建設產能。因此，思考這個問題的方法是，當 Corinne 和她的團隊正在努力增加新生產線並提高產能時，後續產品的生產速度將會更快，因為今天的製造業正在放慢生產速度。因此，我預計，當您考慮多價加強劑的推出時，當您考慮 RSV 到 CMV 的推出時，我們不會處於不利地位。

As you know, as part of our 2020 budget that we did at the end of 2019, we did not plan for pandemic. We were supposed to be commercial several years down the road. And so the team has done a remarkable job to get to this point, but we are -- and we're going to stay for, I would anticipate all over year supply constrained.

如您所知，作為我們在 2019 年底制定的 2020 年預算的一部分，我們沒有為大流行做好準備。我們本應在幾年後實現商業化。因此，團隊已經完成了出色的工作才能達到這一點，但我們 - 並且我們將留下來，我預計全年供應都將受到限制。

Corinne and her team would love to be able to sell more product because trust me, their phone is turning red hot by calls from around the planet and would love to be able to help protect more people, but we just can't because we were not planning a pandemic in 2020. So I anticipate that for variants and for new product launch, we will make sure that we are not capacity constrained, which is why the 3 billion supply volume that some people might think is maybe too aggressive.

科琳和她的團隊希望能夠銷售更多產品，因為相信我，他們的手機因來自世界各地的電話而變得熾熱，並且希望能夠幫助保護更多的人，但我們就是不能，因為我們沒有計劃在2020 年發生大流行。所以我預計，對於變體和新產品的推出，我們將確保我們的產能不受限制，這就是為什麼有些人可能認為30 億的供應量可能過於激進。

As I said in my remarks, the pipeline of the company is also going to pay with this. And so it is just behind the multivalent vaccine. So if you look at a couple of years out, and we're not building manufacturing for 6 months. We're going to be really happy to have that capacity so as we launch product. We can supply the market every single dose that Corinne and her team can make sure that the market wants.

正如我在發言中所說，公司的管道也將為此付出代價。因此它僅次於多價疫苗。因此，如果你看看幾年後，我們將在 6 個月內不會建設製造業。當我們推出產品時，我們將非常高興擁有這種能力。我們可以向市場提供 Corinne 和她的團隊可以確保市場需要的每一種劑量。

Your next response is from Mani Foroohar with SVB Leerink.

您的下一個回復來自 SVB Leerink 的 Mani Foroohar。

One quick one sort of on financials. You gave a little clarity on CapEx investments around expanding capacity reduction. Should we think of that level setting CapEx is going to be forward with a modest increase going forward? Or should we be thinking of that as primarily a onetime build-out?

快速介紹一下財務方面的內容。您對圍繞擴大產能削減的資本支出投資進行了一些澄清。我們是否應該認為設定的資本支出水平將在未來適度增長？或者我們應該將其視為主要是一次性的擴建？

And then secondarily, you've given a little bit of clarity -- and there's a lot of clarity around COGS for this quarter versus rest of the year. Going forward, so we think about the absolute COGS per unit again pretty linearly related to dose. Or are there other attributes, royalties, et cetera, differences in products used between different vaccines, would that suggest if that's not the right way to think about it.

其次，您已經給出了一些清晰的信息，本季度的銷貨成本與今年剩餘時間相比有很多清晰的信息。展望未來，我們再次考慮每單位的絕對 COGS 與劑量呈線性相關。或者是否存在其他屬性、特許權使用費等、不同疫苗之間使用的產品之間的差異，這是否表明這不是正確的思考方式。

Yes. So CapEx, if I understand the question is guidance for '22 and beyond on CapEx. And again, unfortunately, it's a bit early to be able to comment. We -- if you look now, we've increased our guidance for this year based on the developments that have occurred over the last couple of months. Is that a steady state going forward into the future?

是的。因此，資本支出，如果我理解的話，問題是 22 年及以後的資本支出指南。不幸的是，現在發表評論還為時過早。如果你現在看，我們根據過去幾個月發生的事態發展增加了今年的指導。這是未來的穩定狀態嗎？

I think for a company of what will be our size and scope and level of vertical integration, I think it's reasonable to expect that we'll continue to invest in our own capacity. And therefore, you can expect we'll have ongoing CapEx. Is it precisely in this range or somewhat above or below? I really wouldn't want to give you that precision as of yet because we're -- it's not that clear yet. But I think an ongoing CapEx trend will be appropriate for the company.

我認為，對於一家具有我們的規模、範圍和垂直整合水平的公司來說，我認為我們有理由期望我們將繼續投資於我們自己的產能。因此，您可以預期我們將有持續的資本支出。它正好在這個範圍內還是稍微高於或低於這個範圍？到目前為止，我真的不想給你這麼精確的信息，因為我們還不太清楚。但我認為持續的資本支出趨勢適合該公司。

In terms of the COGS, I think that's the right way to think about the cost of manufacturing this product. It will be impacted at some level by the amount of materials in the product. But when you're talking about micrograms of materials, it's really not that significant. So I think you can -- as the simplest assumption assume, it's a pretty steady cost of manufacture as we're seeing right now.

就銷貨成本而言，我認為這是考慮該產品製造成本的正確方法。它會在某種程度上受到產品中材料含量的影響。但當你談論微克的材料時，它實際上並沒有那麼重要。所以我認為你可以 - 正如最簡單的假設假設，正如我們現在所看到的，這是一個相當穩定的製造成本。

Great. And a quick follow-up on some of the contracting. I know it's been asked in various forms. You talked about the OUS manufacturing being about 1/4-ish behind U.S. manufacturing. Right now, based on your disclosures on volume dose, those are delivered versus what we have from the other mRNA competitor in duopoly right now.

偉大的。並對一些合同進行快速跟進。我知道人們以各種形式提出了這個問題。您談到美國製造業大約落後美國製造業 1/4 左右。現在，根據你們對體積劑量的披露，這些劑量是與我們目前從雙寡頭中的其他 mRNA 競爭對手那裡獲得的劑量相比的。

Market share for you guys is somewhere between 5% and 10% and a lot of these countries until you deliver doses. How do you think about catch-up on manufacturing and deliveries and how that influences the ongoing contracting for next year, i.e., does your stronger incumbent position in the U.S. suggest you are better positioned for U.S. contracting volume?

在你們交付劑量之前，你們的市場份額在 5% 到 10% 之間，而且在很多這樣的國家/地區。您如何看待製造和交付的追趕以及這對明年持續簽訂合同的影響，即，您在美國的現有地位是否表明您在美國合同量方面處於更有利的地位？

Or do you think 2021, the results for 2021 contracting have nothing to do with 2022 and every year is a whole new game between you, too?

或者你認為2021年，2021年簽約的結果與2022年無關，每年都是你們之間的全新遊戲？

Yes. It's a good question. So as we said, the plan was always -- the plan we're executing on. And so when we spoke to countries and set up those 21 APAs. we managed the quarter delivery to the countries as we knew capacity would come online. We had not anticipated early parts of the year that we will be able to export from the U.S. And the piece we should not forget is, as you know, it's reported in the media daily, the U.S. is going to be having way too many vaccines very, very soon, if not already.

是的。這是一個好問題。正如我們所說，計劃始終是我們正在執行的計劃。因此，當我們與各國交談並製定這 21 項預約定價安排時。我們管理了向這些國家/地區的季度交付，因為我們知道產能將會上線。我們沒有預料到今年早些時候我們能夠從美國出口。我們不應該忘記的是，正如你所知，媒體每天報導，美國將有太多的疫苗非常非常快，如果還沒有的話。

And so the capacity that we are building in the U.S. and we're adding is also going to supply the world. So I think one should anticipate a very big acceleration of shipments to countries outside the U.S. as we go into Q2 and even more in Q3 and Q4 as we meet our obligation to the U.S. government.

因此，我們在美國建設和增加的產能也將供應全世界。因此，我認為，隨著我們履行對美國政府的義務，進入第二季度，向美國以外國家/地區的發貨量應該會大幅增加，甚至在第三季度和第四季度會增加。

Great. That's really helpful. And could you guys comment on where you are -- what you're seeing in the real world in terms of vaccine hesitant/end market demand. There's been a couple of media reports that, that's starting to be more of a limiting factor as opposed to supply, at least in the U.S. currently, certainly not globally.

偉大的。這真的很有幫助。你們能否評論一下你們在現實世界中在疫苗猶豫/終端市場需求方面所看到的情況。有幾家媒體報導稱，與供應相比，這開始成為更多的限制因素，至少目前在美國是如此，當然不是在全球範圍內。

Correct. In the U.S., and you see it on the daily numbers probably by the CDC people, I think, since mid-April roughly, the number of vaccinations per day in the country is going down. And it is not because of supply. If you look at the shipments coming from the companies, they keep increasing exactly as we have been saying.

正確的。在美國，你可能會在疾病預防控制中心人員的每日數據中看到這一點，我認為，大約從四月中旬開始，該國每天的疫苗接種數量正在下降。這並不是因為供應。如果你看一下這些公司的出貨量，就會發現它們一直在增長，正如我們所說的那樣。

And so now there's an oversupply of vaccine. It's very demand-driven problem now. So you see some states across the country that are still very active in vaccination. And we are looking -- as we said, that very high rates of vaccination is going up every day. There are other parts of the country, as you know, where they have way too many vaccines. As you have heard that the federal government, I think yesterday or the day before, has announced that they we were going to start to shift products from one state to the other based on actual demand and it really need to vaccinate the [discrepancy].

所以現在疫苗供應過剩。現在這是一個非常需求驅動的問題。所以你看到全國一些州的疫苗接種工作仍然非常積極。正如我們所說，我們看到疫苗接種率每天都在上升。如您所知，該國其他地區的疫苗數量過多。正如您所聽說的那樣，聯邦政府，我想昨天或前天已經宣布，我們將開始根據實際需求將產品從一個州轉移到另一個州，並且確實需要消除[差異]。

The U.S. doesn't have a supply of vaccine issue anymore. That was true in January. It is not true anymore.

美國不再存在疫苗供應問題。一月份的情況確實如此。這不再是真的了。

Your next response is from Simon Baker with Redburn.

您的下一個回復來自 Redburn 的 Simon Baker。

Firstly, just going back to the debate around IP waivers. Stephane, as you said that the talk of IP waivers rather misses the point about limited global manufacturing capacity. So to sort of support that, given that you announced you would literally waive IP enforcement back in October. To your knowledge, has any company in the following 7 months sought to exercise that freedom to operate?

首先，回到圍繞知識產權豁免的爭論。 Stephane，正如您所說，關於知識產權放棄的討論並沒有抓住全球製造能力有限的要點。因此，為了支持這一點，考慮到您早在 10 月份就宣布將放棄知識產權執法。據您所知，在接下來的7個月內，是否有任何公司尋求行使這種經營自由？

And also sticking with the vaccine, going back to Slide 28. Do you have data on T cell response over that 6- to 8-month period post primary vaccination for -1273.

還要堅持接種疫苗，回到幻燈片 28。您是否有 -1273 初次接種疫苗後 6 至 8 個月期間 T 細胞反應的數據。

And then just a quick question on the financials. David, I think you mentioned that -- in the SG&A in Q1, there were some costs related to effectively start-up of good supply. I just wondered if you could give us any color on the nonrecurring one-off elements of SG&A in Q1 as we think about evolution across the year.

然後是一個關於財務的簡單問題。大衛，我想你提到過——在第一季度的銷售及管理費用中，存在一些與有效啟動良好供應相關的成本。我只是想知道，當我們考慮全年的演變時，您是否能為我們提供有關第一季度 SG&A 的非經常性一次性元素的任何信息。

Thank you so much. I'll take the first one on IP and Stephen will take the T cell and David the financials.

太感謝了。我將選擇第一個關於 IP 的問題，Stephen 將選擇 T 細胞，而 David 將選擇財務方面的問題。

So I'm not aware of any company of size that is going after [Moderna]. Again, going back to what I described. One would have first to figure out how to make -- managing IP before asking the regulators to start the clinical study. And that doesn't happen quickly. We are monitoring the field very closely as we always have. But at this stage, happy that this is really not the point that will impact. Of course, '21 is possible, but even '22. Stephen, on T cell.

所以我不知道有任何規模的公司正在追逐[Moderna]。再次回到我所描述的。在要求監管機構開始臨床研究之前，人們必須首先弄清楚如何管理知識產權。這不會很快發生。我們一如既往地密切關注這一領域。但現階段，慶幸的是這確實不是會產生影響的點。當然，'21 是可能的，但甚至'22 也是可能的。斯蒂芬，關於 T 細胞。

So the data we have from today is the initial analysis on the boosters. We are -- as we previously announced, we've been looking at a study ourselves and with the NIH. They are running a primary series vaccination study and also looking at other elements. And so we will perhaps get T cell data in the midterm. But at this point, we do not have any T cell data yet on the boosters. We do have ongoing studies with NIH on -- in general, our Phase I and our own Phase II. And if it becomes important in the future, we can obviously look at T cell responses with waning immunity out 6, 12 months in those studies as well.

所以我們今天得到的數據是對助推器的初步分析。正如我們之前宣布的，我們一直在與美國國立衛生研究院一起研究一項研究。他們正在進行一項初步系列疫苗接種研究，並研究其他因素。因此，我們也許會在中期獲得 T 細胞數據。但目前，我們還沒有任何關於增強劑的 T 細胞數據。總的來說，我們確實與 NIH 正在進行第一階段和第二階段的研究。如果它在未來變得重要，我們顯然也可以在這些研究中觀察 6、12 個月後免疫力減弱的 T 細胞反應。

We don't have a specific plan to do that at this point. But we are pretty encouraged by the historical correlation between our previously reported T cell data and public T cell data and the neutralizing titers that are obviously much easier to measure over time across a wider range of subjects in T cells. And David?

目前我們還沒有具體的計劃來做到這一點。但我們對之前報告的T 細胞數據和公共T 細胞數據之間的歷史相關性以及中和滴度之間的歷史相關性感到非常鼓舞，這些中和滴度顯然更容易隨著時間的推移在更廣泛的T 細胞受試者中進行測量。大衛呢？

Yes. So in terms of the expenses we incurred in the first quarter, including in commercial, yes, we had some onetime expenses to set up businesses around the world. But the preponderance of the total operating expenses, including in commercial, I would say, will continue. And therefore, that's why I gave you some guidance that, if you start at that $0.5 billion spend level in the first quarter and the fourth of last year, we're expecting now to see that trend up notably, as we move forward through the year, which we thought it would start sooner, but we now expect we'll start in the second quarter. So running a business of this size on a global basis, we think that, that spend level is quite reasonable, to be honest.

是的。因此，就我們第一季度產生的費用（包括商業費用）而言，是的，我們有一些一次性費用用於在世界各地建立業務。但我想說的是，總運營支出（包括商業支出）的主導地位將繼續存在。因此，這就是為什麼我給了你們一些指導，如果你們從去年第一季度和去年第四季度的 5 億美元支出水平開始，我們預計現在隨著我們向前邁進，這一趨勢會顯著上升。今年，我們原以為會更早開始，但現在預計將在第二季度開始。因此，老實說，在全球範圍內經營如此規模的企業，我們認為這一支出水平是相當合理的。

I'm showing no further questions at this time. I would now like to turn the conference back over to Stephane Bancel.

我目前沒有提出任何進一步的問題。我現在想把會議轉回給斯蒂芬·班塞爾。

Thank you so much for participating in to this call and for the great questions. We look forward to seeing you at Times Day on May 27. Stay safe, everybody. Have a nice day. Bye.

非常感謝您參與本次電話會議並提出重要問題。我們期待 5 月 27 日在 Times Day 見到您。大家注意安全。祝你今天過得愉快。再見。

Ladies and gentlemen, this concludes today's conference. Thank you for your participation. You have a wonderful day, and you may all disconnect.

女士們、先生們，今天的會議到此結束。感謝您的參與。你們度過了美好的一天，但你們可能都會斷開連接。