莫德納 (MRNA) 2022 Q3 法說會逐字稿

Good morning. My name is Kevin, and welcome to Moderna's Third Quarter 2022 Earnings Call. (Operator Instructions)

早上好。我的名字是凱文，歡迎來到 Moderna 的 2022 年第三季度財報電話會議。 （操作員說明）

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

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

Thank you, Kevin. Good morning, everyone, and thank you for joining us on today's call to discuss Moderna's Third Quarter 2022 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，凱文。大家早上好，感謝您加入我們今天的電話會議，討論 Moderna 的 2022 年第三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，訪問今天上午發布的新聞稿以及我們將審查的幻燈片。

On today's call are Stéphane Bancel, our Chief Executive Officer; Stephen Hoge, our President; Arpa Garay, our Chief Commercial Officer; and Jamie Mock, our Chief Financial Officer. After prepared remarks, we will take your questions through 9:15 a.m. this morning.

今天的電話是我們的首席執行官 Stéphane Bancel；我們的總裁斯蒂芬·霍格； Arpa Garay，我們的首席商務官；和我們的首席財務官 Jamie Mock。準備好發言後，我們將在今天上午 9 點 15 分之前回答您的問題。

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

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》的安全港條款作出的前瞻性陳述。請參閱隨附演示文稿的幻燈片 2 和我們提交給 SEC 的重要風險因素可能導致我們的實際業績和結果與這些前瞻性陳述中明示或暗示的內容存在重大差異。有了這個，我會把電話轉給 Stéphane。

Thank you, Lavina. Good morning or good afternoon everyone. Welcome to our Q3 2022 conference call. Today, I will start with a quick business review of the quarter before Stephen reviews our clinical programs. Arpa will then take you through commercial dynamics, and Jamie will present financials. I will then come back to close before we take your questions.

謝謝你，拉維娜。大家早上好或下午好。歡迎來到我們的 2022 年第三季度電話會議。今天，在斯蒂芬審查我們的臨床項目之前，我將首先對本季度的業務進行快速回顧。 Arpa 將帶您了解商業動態，Jamie 將介紹財務狀況。在我們回答你的問題之前，我會回來結束。

In the quarter, we reported $3.4 billion in revenues. We reported net income of $1 billion and cash investments totaling $17 billion. We now expect deliveries under advanced purchase agreements in the range of $18 billion to $19 billion in 2022 due to delayed deliveries from our Fill/Finish contract manufacturers, resulting in $2 billion to $3 billion of revenue deferrals into 2023.

本季度，我們報告了 34 億美元的收入。我們報告的淨收入為 10 億美元，現金投資總額為 170 億美元。由於我們的填充/完成合同製造商延遲交付，我們現在預計 2022 年根據預先採購協議的交付量在 180 億美元至 190 億美元之間，導致 20 億美元至 30 億美元的收入推遲到 2023 年。

In Q3, we had to deal with a lot of complexity, launching 2 products, 1273.214 and 1273.222 at the same time and also moving products from 10-dose vials to 5-dose vials. Q3 was actually our greater delivery amount in terms of vials produced and was up about 20%, the average of the previous 3 quarters. Arpa will share more thoughts on 2023 in a moment.

在第三季度，我們不得不處理很多複雜性，同時推出 1273.214 和 1273.222 兩種產品，並將產品從 10 劑小瓶轉移到 5 劑小瓶。就生產的小瓶而言，第三季度實際上是我們更大的交付量，增長了約 20%，是前三個季度的平均值。 Arpa 稍後將分享更多關於 2023 年的想法。

In the third quarter, we repurchased over 7 million shares. The $3 billion share repurchase program we announced in February 2022 was completed. Since the start of our first share repurchase program in 2021 through the end of the third quarter, we have repurchased more than 23 million shares. Our first share repurchase program announced in August 2022 for an additional $3 billion in repurchase is ongoing.

第三季度，我們回購了超過700萬股。我們在 2022 年 2 月宣布的 30 億美元股票回購計劃已經完成。自 2021 年首次股票回購計劃啟動至第三季度末，我們已回購超過 2300 萬股股票。我們於 2022 年 8 月宣布的第一個股票回購計劃正在進行中，額外的 30 億美元回購。

Let me now review the pipeline highlights and advances since our last update. I am very pleased with the important progress the Moderna team has made on advancing the pipeline closer to product launches, and at the same time, increasing the breadth of the pipeline. We continue to progress with COVID booster programs and have received authorization around the world for both of COVID 1273.214 program which target Omicron BA.1 and 1273.222, which target BA.4/5.

現在讓我回顧一下自上次更新以來管道的亮點和進展。我對 Moderna 團隊在推進產品線更接近產品發布方面取得的重要進展感到非常高興，同時增加了產品線的廣度。我們繼續推進 COVID 助推器計劃，並已獲得全球範圍內針對 Omicron BA.1 的 COVID 1273.214 計劃和針對 BA.4/5 的 1273.222 的授權。

We have, as you know, two respiratory vaccines in Phase III trials as we speak that continue to progress quickly.

如您所知，正如我們所說，我們有兩種呼吸道疫苗處於 III 期試驗中，並且繼續迅速取得進展。

For flu vaccine, at R&D in September, we announced the first Phase III immunogenicity study was fully enrolled. We expect now data in the first quarter of 2023. As a reminder, we plan to pursue an accelerated approval pathway for seasonal flu vaccine. We also started a Phase III efficacy study with a flu vaccine, and that trial is enrolling quickly.

對於流感疫苗，在 9 月份的研發中，我們宣布第一個 III 期免疫原性研究已全部入組。我們預計現在的數據將在 2023 年第一季度發布。提醒一下，我們計劃加快季節性流感疫苗的批准途徑。我們還開始了一項針對流感疫苗的 III 期療效研究，該試驗正在迅速招募中。

For Phase III [allergy] vaccine, we are on track for data readout this winter season. We were pleased to announce that Merck exercised their option to develop and commercialize our personal cancer vaccine, mRNA-4157, paying more than $250 million in Q4. We and Merck will share costs and profit 50-50 for this program moving forward. We continue to expect data from our Phase II study for PCV in Q4 this year.

對於 III 期 [過敏] 疫苗，我們有望在今年冬季公佈數據。我們很高興地宣布，默克公司行使了他們開發和商業化我們的個人癌症疫苗 mRNA-4157 的選擇權，在第四季度支付了超過 2.5 億美元。我們和默克將分擔該計劃向前發展的 50-50 的成本和利潤。我們繼續期待我們在今年第四季度對 PCV 進行 II 期研究的數據。

In rare diseases, we are pleased to share at the R&D Day that we saw encouraging early signs of clinical benefit from both PA and GSD1a and announced a new development candidate for OTC.

在罕見病領域，我們很高興在研發日上分享我們看到 PA 和 GSD1a 臨床獲益的令人鼓舞的早期跡象，並宣布了 OTC 的新開發候選者。

On Slide 6, you see our usual snapshot of Moderna in November 2022, showing the breadth of the pipeline, with now 48 programs in development across vaccines and therapeutics. The company continues to grow and we are now at more than 3,700 Moderna team members.

在幻燈片 6 上，您可以看到我們通常在 2022 年 11 月對 Moderna 的快照，顯示了該管道的廣度，目前有 48 個項目正在開發中，涉及疫苗和治療。公司不斷發展壯大，我們現在擁有 3,700 多名 Moderna 團隊成員。

Last week, we are very pleased to announce as a top employer by science for the eighth consecutive year. We have now 15 commercial subsidiaries globally and a strong balance sheet of $17 billion to fund our continued growth. With this, I will now turn over to Stephen to review the pipeline. Stephen?

上週，我們很高興地宣布連續第八年被科學評為最佳雇主。我們現在在全球擁有 15 家商業子公司和 170 億美元的強勁資產負債表，為我們的持續增長提供資金。有了這個，我現在將交給斯蒂芬來審查管道。斯蒂芬?

Thank you, Stéphane. Good morning or good afternoon, everyone. This morning, I'll review our clinical progress. We've launched 2 vaccine boosters for the current fall/winter season to meet different market demands and have received authorizations or approvals worldwide for these vaccines. We previously shared that 1273.214, which targets Omicron BA.1 induced significantly higher titers than 1273 against the BA.1 and BA.4/5 sublineages in the clinical trial. And mRNA-1273.214 is now authorized in the United Kingdom, Switzerland, Canada, Australia, European Union, Japan and other countries.

謝謝你，斯蒂芬。大家早上好或下午好。今天早上，我將回顧我們的臨床進展。我們針對當前的秋冬季節推出了 2 款疫苗助推器，以滿足不同的市場需求，並已在全球範圍內獲得了這些疫苗的授權或批准。我們之前分享了針對 Omicron BA.1 的 1273.214 在臨床試驗中針對 BA.1 和 BA.4/5 亞系誘導的滴度顯著高於 1273。而mRNA-1273.214現已在英國、瑞士、加拿大、澳大利亞、歐盟、日本等國家獲得授權。

For mRNA-1273.222, which targets the Omicron BA.4/5 variants, the Phase II/III study is ongoing, and we expect data later this quarter. MRNA-1273.222 is authorized in the United States and now also in the United Kingdom, Switzerland, Australia, Canada, the European Union, Japan and other countries.

對於針對 Omicron BA.4/5 變體的 mRNA-1273.222，II/III 期研究正在進行中，我們預計本季度晚些時候會有數據。 MRNA-1273.222在美國獲得授權，現在也在英國、瑞士、澳大利亞、加拿大、歐盟、日本等國家獲得授權。

Now moving to Slide 9. I'll review our respiratory vaccines pipeline. I will cover the Phase III studies in detail on the next slide. Here, I want to highlight the progress in the earlier-stage studies with our respiratory vaccines. MRNA-1020, 10.30 for seasonal influenza is in a Phase I/II study and is now fully enrolled. MRNA 1345 for RSV in the pediatric population is now fully enrolled in a Phase I study.

現在轉到幻燈片 9。我將回顧一下我們的呼吸道疫苗管道。我將在下一張幻燈片中詳細介紹 III 期研究。在這裡，我想強調一下我們的呼吸道疫苗在早期研究中取得的進展。用於季節性流感的 MRNA-1020, 10.30 處於 I/II 期研究中，現已完全註冊。用於兒科人群 RSV 的 MRNA 1345 現在已完全參與 I 期研究。

Moving now to our combination respiratory pipeline, where we have made meaningful progress, mRNA-1073, our combination vaccine for COVID and flu, is in Phase I/II and is fully enrolled. I'm very pleased to announce that our combination COVID, flu and RSV vaccine, or mRNA-1230, has also started enrolling in its Phase I/II study. We announced a new development candidate, mRNA-1045, this one targeting combination of RSV and influenza, and that has started in its Phase I/II study.

現在轉到我們的聯合呼吸管道，我們已經取得了有意義的進展，我們的 COVID 和流感聯合疫苗 mRNA-1073 正處於 I/II 階段，並且已完全註冊。我很高興地宣布，我們的 COVID、流感和 RSV 聯合疫苗或 mRNA-1230 也已開始參加其 I/II 期研究。我們宣布了一種新的開發候選藥物 mRNA-1045，這是一種針對 RSV 和流感的組合，並已開始其 I/II 期研究。

And lastly, in our combination vaccine pipeline, we also have a pediatric vaccine covering hMPV and PIV3 that study is ongoing in the fully enrolled Phase Ib study.

最後，在我們的聯合疫苗管道中，我們還有一種涵蓋 hMPV 和 PIV3 的兒科疫苗，該研究正在完全註冊的 Ib 期研究中進行。

Finally, our endemic human coronavirus vaccine is in preclinical development, along with our pediatric RSV, HMPV combination vaccine.

最後，我們的地方性人類冠狀病毒疫苗以及我們的兒科 RSV、HMPV 聯合疫苗正處於臨床前開發階段。

Now to review our Phase III flu and RSV programs on Slide 10. For flu, our Phase III immunogenicity study in the Southern Hemisphere is fully enrolled with 6,000 participants with the data readout expected in the first quarter of 2023. As we've previously noted, regulators have indicated support for an accelerated approval pathway for our seasonal flu vaccine candidate, pending the study -- the results from this study. We've also started enrolling our Phase III efficacy study in the Northern Hemisphere and have now enrolled more than 10,000 participants. Timing of this confirmatory Phase III efficacy readout will be driven by flu case accruals in the study and could come as early as this winter.

現在在幻燈片 10 上回顧我們的 III 期流感和 RSV 計劃。對於流感，我們在南半球的 III 期免疫原性研究已完全招募 6,000 名參與者，預計在 2023 年第一季度公佈數據。正如我們之前指出的，監管機構已表示支持我們的季節性流感疫苗候選者的加速批准途徑，等待研究 - 這項研究的結果。我們還開始在北半球招募我們的 III 期療效研究，現在已經招募了 10,000 多名參與者。這一確認性 III 期療效讀數的時間安排將由研究中的流感病例累積驅動，最早可能在今年冬天到來。

Looking to RSV. Our pivotal Phase III efficacy study in older adults has now enrolled more than 35,000 participants. As we previously mentioned, our primary endpoints in this study are safety and vaccine efficacy. Timing of the Phase III efficacy readout will be driven by RSV case accruals in that study. As we're now in the midst of a very strong RSV season, we continue to expect that the result will be available this winter season.

期待 RSV。我們在老年人中開展的關鍵 III 期療效研究現已招募了超過 35,000 名參與者。正如我們之前提到的，我們在這項研究中的主要終點是安全性和疫苗功效。 III 期療效讀數的時間將由該研究中的 RSV 病例累積驅動。由於我們現在正處於一個非常強勁的 RSV 季節，我們繼續期待結果將在今年冬季公佈。

Moving on to our latent and public health vaccine portfolio. Our CMV vaccine is ongoing in a Phase III study. Our EBV vaccine to prevent infectious mononucleosis is in a Phase I study, while our EBV vaccine to prevent longer-term sequelae such as cancer and multiple sclerosis is in preclinical.

繼續我們的潛伏和公共衛生疫苗組合。我們的 CMV 疫苗正在進行 III 期研究。我們用於預防傳染性單核細胞增多症的 EBV 疫苗處於 I 期研究中，而我們用於預防癌症和多發性硬化等長期後遺症的 EBV 疫苗處於臨床前研究階段。

We have 2 HIV Phase I trials ongoing, and our HSV and VZV vaccines are in ongoing preclinical studies. Finally, our public health vaccine for Zika is ongoing in a Phase II trial and our Nipah vaccine is ongoing in a Phase I study.

我們正在進行 2 項 HIV I 期試驗，我們的 HSV 和 VZV 疫苗正在進行臨床前研究。最後，我們的寨卡公共衛生疫苗正在進行 II 期試驗，我們的 Nipah 疫苗正在進行 I 期研究。

Now let's take a look at our therapeutics pipeline on Slide 12. First, I want to note that AstraZeneca notified us that after a portfolio review, they are returning the rights to the IL-12 program to us. They are concluding the Phase I study, and we will then evaluate next steps for the program for ourselves.

現在讓我們在幻燈片 12 上看一下我們的治療管道。首先，我想指出，阿斯利康通知我們，在對投資組合進行審查後，他們正在將 IL-12 項目的權利歸還給我們。他們正在結束第一階段的研究，然後我們將自己評估該計劃的下一步。

Second, we're excited that our checkpoint vaccine has started dosing its first patient in a Phase I study. And finally, our partner, Vertex, expects to submit an IND for our mRNA cystic fibrosis program by the end of this year. We recently shared updates on our personalized cancer vaccine, PA and GSD1a programs at our latest R&D day and I will talk to those in more detail in the upcoming slides.

其次，我們很高興我們的檢查點疫苗已經開始在 I 期研究中給第一名患者服用。最後，我們的合作夥伴 Vertex 預計將在今年年底之前為我們的 mRNA 囊性纖維化項目提交一份 IND。我們最近在最近的研發日分享了我們的個性化癌症疫苗、PA 和 GSD1a 計劃的更新，我將在接下來的幻燈片中更詳細地討論這些內容。

Now recall at R&D Day that we shared data from 2 rare disease programs. The first is in our propionic acidemia program, which is a multi-dose study. And as of September, we had accrued 6 patient years of experience on the drug and administered well over 100 doses. It has generally been well tolerated, which is encouraging. We've also seen an encouraging trend in the reduction of biomarkers and been observing a numerical decrease in the frequency of metabolic decompensation events, which is also really encouraging given the severity of these events for propionic acidemia patients.

現在回想一下，我們在研發日分享了來自 2 個罕見病項目的數據。第一個是我們的丙酸血症計劃，這是一項多劑量研究。截至 9 月，我們已經積累了 6 年的患者使用該藥物的經驗，並施用了超過 100 劑。它通常被很好地容忍，這是令人鼓舞的。我們還看到了生物標誌物減少的令人鼓舞的趨勢，並且觀察到代謝失代償事件發生頻率的數字下降，考慮到丙酸血症患者這些事件的嚴重性，這也確實令人鼓舞。

In the GSD1a program, we shared an early set of data from the first 2 patients in the first cohort. The study is a single ascending dose study that runs a fasting challenge in a controlled and safe environment in patients with GSD1a who are unable to normally fast or go without food for long periods of time without becoming hypoglycemic. Both patients in the first cohort have demonstrated that mRNA-3745 was well tolerated and showed an extension of fast duration and normalization of key biomarkers, including glucose, which we think is very encouraging signal of activity.

在 GSD1a 計劃中，我們分享了第一組前 2 名患者的一組早期數據。該研究是一項單次遞增劑量研究，在受控和安全的環境中對 GSD1a 患者進行禁食挑戰，這些患者無法正常禁食或長時間不進食而不會出現低血糖。第一個隊列中的兩名患者都證明 mRNA-3745 具有良好的耐受性，並顯示出包括葡萄糖在內的關鍵生物標誌物的快速持續時間和正常化，我們認為這是非常令人鼓舞的活動信號。

To close, I wanted to remind everyone that we expect our Phase II results from our personalized cancer therapeutic by the end of the year. The randomized study comparing PCV plus KEYTRUDA versus KEYTRUDA alone enrolled approximately 150 resected melanoma patients with a high risk of recurrence. The primary endpoint is to prevent is recurrence-free survival.

最後，我想提醒大家，我們期待我們的個性化癌症治療在今年年底前獲得 II 期結果。比較 PCV 加 KEYTRUDA 與單獨 KEYTRUDA 的隨機研究招募了大約 150 名具有高複發風險的切除黑色素瘤患者。主要終點是預防無復發生存。

As Stéphane mentioned earlier, our partner, Merck exercised the option to jointly develop and commercialize mRNA-4157, and we look forward to sharing that data this quarter. With that, I will hand it over to Arpa.

正如 Stéphane 之前提到的，我們的合作夥伴默克公司行使了共同開發和商業化 mRNA-4157 的選擇權，我們期待在本季度分享這些數據。有了這個，我會把它交給Arpa。

Thank you, Stephen, and good day to everyone. I will start with a review of sales on Slide 16. Sales to the U.S. were $1 billion in the third quarter and were mainly from deliveries of mRNA-1273.222, our bivalent booster targeting Omicron BA.4/5. Sales to Europe of mRNA-1273.214 were also $1 billion and the rest of the world totaled $1.1 billion. Through the first 3 quarters of the year, U.S. sales were $3.4 billion, sales to Europe were $4.5 billion and sales to the rest of the world accounted for $5.7 billion.

謝謝你，斯蒂芬，祝大家有美好的一天。我將從幻燈片 16 的銷售回顧開始。第三季度對美國的銷售額為 10 億美元，主要來自 mRNA-1273.222 的交付，這是我們針對 Omicron BA.4/5 的二價助推器。 mRNA-1273.214 對歐洲的銷售額也為 10 億美元，世界其他地區的銷售額為 11 億美元。今年前三個季度，美國銷售額為 34 億美元，對歐洲的銷售額為 45 億美元，對世界其他地區的銷售額為 57 億美元。

In both the 3- and 9-month periods, we saw geographical diversification of sales across these key regions.

在 3 個月和 9 個月期間，我們看到這些關鍵地區的銷售地域多元化。

We recognize there are questions regarding the 2023 market and long-term COVID booster potential and we wanted to walk you through how we are thinking about it. As we transition into an endemic market, there are important factors we considered in our commercial outlook. These include the ongoing medical need for COVID boosters and the potential size of the annual booster market. We use the seasonal flu market to frame the opportunity, and I will take you through our thinking on that in the next couple of slides. I will also detail some of the factors underlying the transition to the commercial market in the U.S. in 2023. I'll then wrap up the COVID section with an overview of our currently signed contracts and our outlook for additional expected contracts in 2023. Finally, I'll close with a reminder of what's coming in 2023 from our respiratory vaccine franchise a potential launch timings that we shared recently at our R&D Day in September.

我們認識到存在關於 2023 年市場和長期 COVID 助推器潛力的問題，我們希望引導您了解我們是如何考慮的。當我們過渡到一個地方性市場時，我們在商業前景中考慮了一些重要因素。其中包括對 COVID 助推器的持續醫療需求以及年度助推器市場的潛在規模。我們利用季節性流感市場來構建機會，我將在接下來的幾張幻燈片中向您介紹我們對此的思考。我還將詳細介紹 2023 年美國向商業市場過渡的一些因素。然後，我將概述我們目前簽署的合同以及我們對 2023 年其他預期合同的展望，以結束 COVID 部分。最後，最後，我將提醒大家 2023 年我們的呼吸道疫苗專營權將會發生什麼，這是我們最近在 9 月的研發日分享的潛在發佈時間。

So starting with the medical need for COVID boosters, the chart on Slide 18 compares hospitalizations and deaths associated with the seasonal flu and COVID over a relevant time period. For flu, we looked back at the past 10 influenza seasons in the U.S. before COVID-related interventions disrupted the typical flu season. And for COVID, we looked at hospitalizations and deaths from October 2021 to September 2022, which covers the period of widespread immunity against SARS-CoV-2 and its variants either through vaccination or infection. We believe this period is a close proxy to what population immunity to COVID could be in an endemic season.

因此，從對 COVID 助推器的醫療需求開始，幻燈片 18 上的圖表比較了相關時間段內與季節性流感和 COVID 相關的住院和死亡人數。對於流感，我們回顧了美國過去 10 個流感季節，之後與 COVID 相關的干預措施破壞了典型的流感季節。對於 COVID，我們研究了 2021 年 10 月至 2022 年 9 月的住院和死亡人數，這涵蓋了通過疫苗接種或感染對 SARS-CoV-2 及其變體廣泛免疫的時期。我們認為，這一時期是流行季節人群對 COVID 免疫力的密切代表。

As you can see here on the chart, hospitalizations due to COVID during the past 12 months are 3x higher than the 2017, 2018 flu season, which represents the year with the highest medical burden within the 10-year period included in the analysis. And the deaths due to COVID are even higher, coming in at a rate of 7x higher than the same severe flu season. This comparison shows the higher medical burden of COVID in a period that we believe more closely approximates an endemic season and underscores the need for boosters in the endemic phase. It also helps frame the potential endemic annual COVID market, which I want to take you through on the next slide.

正如您在圖表中看到的那樣，過去 12 個月因 COVID 住院的人數是 2017 年和 2018 年流感季節的 3 倍，這代表了分析中包含的 10 年內醫療負擔最高的一年。新冠病毒導致的死亡人數甚至更高，比同一個嚴重流感季節高出 7 倍。這一比較表明，在我們認為更接近流行季節的時期內，COVID 的醫療負擔較高，並強調在流行階段需要加強劑。它還有助於構建潛在的地方性年度 COVID 市場，我想在下一張幻燈片中向您介紹。

To size the endemic COVID booster market, we start with the flu market volumes. Volume in the annual flu market is approximately 500 million to 600 million doses around the world. The size of the market is highly dependent on the number of doses as well as global price as shown in the sensitivity table on the left-hand side of the slide. The prices shown here are purely illustrative to demonstrate a range of outcomes on global pricing. Ultimately, global price for COVID boosters will reflect sales mix and differential pricing across markets.

為了確定流行的 COVID 助推器市場規模，我們從流感市場數量開始。全球每年流感市場的銷量約為 5 億至 6 億劑。如幻燈片左側的敏感度表所示，市場規模在很大程度上取決於劑量數量和全球價格。此處顯示的價格純粹是為了說明全球定價的一系列結果。最終，COVID 助推器的全球價格將反映不同市場的銷售組合和差異定價。

Our endemic pricing will be focused on the value that the vaccine brings to health care systems around the world.

我們的地方性定價將側重於疫苗為全球醫療保健系統帶來的價值。

As we move to an endemic market in 2023, key factors that will impact our volume in the year include the medical need, ongoing viral evolution, recommendations from public health authorities and consumer motivation to vaccinate. So while we believe that volumes in the global endemic COVID market should approximate to at least 600 million doses over time, we believe it is too early to reliably predict the variables impacting the volume of doses in 2023.

隨著我們在 2023 年進入流行市場，影響我們今年銷量的關鍵因素包括醫療需求、持續的病毒進化、公共衛生當局的建議和消費者接種疫苗的動機。因此，儘管我們認為隨著時間的推移，全球流行的 COVID 市場的劑量應至少接近 6 億劑，但我們認為，現在要可靠地預測影響 2023 年劑量量的變量還為時過早。

Turning to Slide 20 and specifically addressing the transition to the commercial market in the U.S. We anticipate a more fragmented customer base, including private payers, health plans, pharmacy chains, individual pharmacies and physician offices. We also anticipate reduced predictability in orders, seasonality of deliveries similar to flu vaccine deliveries, a shift to full distribution costs assumed by Moderna as well as other major factors in the U.S. such as shifting to a single dose presentation and continued innovation and product differentiation.

轉到幻燈片 20，具體解決美國向商業市場的過渡。我們預計客戶群會更加分散，包括私人付款人、健康計劃、藥房連鎖店、個體藥房和醫生辦公室。我們還預計訂單的可預測性降低、類似於流感疫苗交付的季節性交付、Moderna 承擔的全部分銷成本的轉變以及美國的其他主要因素，例如轉向單劑量呈現以及持續創新和產品差異化。

Moving on to Slide 21, we summarize the contracts that have been signed so far for 2023. We had advanced purchase agreements for the United Kingdom, Canada, Switzerland, Taiwan and Kuwait, totaling $2.5 billion. Additionally, we expect deferrals of $2 billion to $3 billion from 2022. These deferrals are from the countries listed on the slide. Together, these advanced purchase agreements and deferrals totaled $4.5 billion to $5.5 billion in sales for 2023.

轉到幻燈片 21，我們總結了迄今為止已簽署的 2023 年合同。我們為英國、加拿大、瑞士、台灣和科威特簽訂了總額為 25 億美元的預購協議。此外，我們預計從 2022 年起延期 20 億至 30 億美元。這些延期來自幻燈片上列出的國家。到 2023 年，這些提前購買協議和延期購買的總銷售額為 45 億至 55 億美元。

Finally and very importantly, we have a number of countries where we expect additional 2023 contracts to be signed. We are working to secure 23 orders in the U.S., EU, Japan, Australia, Asia, Latin America and COVAX. And we expect to have visibility into these orders as contracting season begins later this quarter and continuing into next year.

最後也是非常重要的一點，我們預計將在許多國家簽署額外的 2023 年合同。我們正在努力爭取在美國、歐盟、日本、澳大利亞、亞洲、拉丁美洲和 COVAX 的 23 個訂單。隨著合同季節從本季度晚些時候開始並持續到明年，我們希望能夠了解這些訂單。

So to summarize the COVID outlook on Slide 22, with the continued higher medical burden of COVID relative to flu, we expect the endemic COVID vaccine market could be as large or larger than flu market volumes over time. The U.S. market is transitioning to a commercial market and we believe we are well-positioned to serve its evolving needs. And finally, we have established a base of confirmed contracts of $4.5 billion to $5.5 billion in 2023, to which we anticipate adding a number of important orders in the months ahead from key markets, including the U.S., EU, Japan and others.

因此，總結幻燈片 22 上的 COVID 前景，隨著 COVID 相對於流感的醫療負擔持續升高，我們預計隨著時間的推移，地方性 COVID 疫苗市場可能與流感市場數量一樣大或更大。美國市場正在向商業市場過渡，我們相信我們已做好準備滿足其不斷變化的需求。最後，我們已經建立了 2023 年 45 億至 55 億美元的已確認合同基礎，我們預計未來幾個月將增加來自美國、歐盟、日本等主要市場的一些重要訂單。

Now before I close, I'm excited to review the formation of our respiratory vaccine franchise that we highlighted during our R&D Day in September. As early as next year, we could be expanding into flu and RSV. And as we look at flu and RSV, combined with COVID, they lead to more deaths annually than Alzheimer's, stroke or diabetes in developed markets. As Stephen highlighted, depending on case accruals and vaccine efficacy, we could see data from our flu and RSV Phase III trials this winter. We are actively preparing for the commercial launches for these additional respiratory vaccines and will leverage the COVID commercial infrastructure that we are currently building. With that, I'd like to turn it over to Jamie.

現在在我結束之前，我很高興回顧一下我們在 9 月研發日期間強調的呼吸道疫苗專營權的形成。最早在明年，我們可能會擴展到流感和 RSV。當我們觀察流感和 RSV 以及 COVID 時，它們每年導致的死亡人數超過發達市場的阿爾茨海默氏症、中風或糖尿病。正如斯蒂芬強調的那樣，根據病例增加和疫苗效力，我們可以看到今年冬天流感和 RSV III 期試驗的數據。我們正在積極準備這些額外呼吸道疫苗的商業發布，並將利用我們目前正在建設的 COVID 商業基礎設施。有了這個，我想把它交給傑米。

Thank you, Arpa, and hello, everyone. It's a pleasure to be here with you today. After 2 months at Moderna, I am even more excited about our company's future and the role we are playing in bringing a new generation of medicines to patients. For those of you whom I haven't had the pleasure of meeting yet, I look forward to working with you in the months and years ahead.

謝謝你，Arpa，大家好。很高興今天和你在一起。在 Moderna 工作了 2 個月後，我對我們公司的未來以及我們在為患者帶來新一代藥物方面所扮演的角色更加興奮。對於那些我尚未有幸見到的人，我期待在未來的幾個月和幾年裡與你們一起工作。

Today, I will start by providing additional color on our third quarter results and capital allocation priorities and finish with the view on the key drivers on our remaining 2022 financial performance.

今天，我將首先為我們的第三季度業績和資本分配優先事項提供額外的色彩，最後是對我們剩餘的 2022 年財務業績的關鍵驅動因素的看法。

Turning now to Slide 25. Total product sales in the quarter of $3.1 billion decreased 35% year-over-year. The decrease was driven by lower sales volumes due to the timing of market authorizations, for our updated COVID-19 booster vaccines and the related manufacturing ramp-up with our CMO partners. As a reminder, we received the marketing authorization for the U.S. on August 31, for the European Union on September 2, and Japan on September 12.

現在轉到幻燈片 25。本季度的產品總銷售額為 31 億美元，同比下降 35%。下降的原因是由於我們更新的 COVID-19 加強疫苗的市場授權時間以及與我們的 CMO 合作夥伴的相關製造量增加，導致銷量下降。提醒一下，我們於 8 月 31 日獲得了美國的上市許可，9 月 2 日獲得了歐盟的上市許可，9 月 12 日獲得了日本的上市許可。

We anticipate that product sales will be higher in the fourth quarter of 2022 than in the third quarter as we continue to deliver against our supply contracts for booster vaccines. Cost of sales was 35% of product sales compared to 15% of product sales last year. This includes a charge of $333 million for inventory write-downs related to excess and obsolete COVID-19 products and expense for unutilized manufacturing capacity of $209 million and a loss on firm purchase commitments and related cancellation charges of $102 million. These charges are driven by a shift in product demand to our Omicron-targeting COVID-19 bivalent boosters and costs associated with surplus production capacity.

我們預計 2022 年第四季度的產品銷售額將高於第三季度，因為我們將繼續按照加強疫苗的供應合同交付。銷售成本佔產品銷售額的 35%，而去年佔產品銷售額的 15%。這包括與過剩和過時的 COVID-19 產品相關的庫存減記費用 3.33 億美元，未使用的製造能力費用為 2.09 億美元，確定採購承諾損失和相關取消費用為 1.02 億美元。這些費用是由產品需求轉向我們以 Omicron 為目標的 COVID-19二價助推器以及與產能過剩相關的成本推動的。

Research and development expenses were $820 million, an increase of 57% versus the prior year. The increase in R&D spend continues to be driven by our increasing and maturing pipeline, including Phase III studies for RSV, flu, CMV and COVID boosters.

研發費用為 8.2 億美元，同比增長 57%。研發支出的增加繼續受到我們不斷增加和成熟的管道的推動，包括 RSV、流感、CMV 和 COVID 助推器的 III 期研究。

Selling, general and administration expenses of $278 million increased by 65% year-over-year. The growth in spending was driven by continued investments in personnel and outside services in support of the accelerated commercial and overall company build-out.

銷售、一般和管理費用為 2.78 億美元，同比增長 65%。支出的增長是由對人員和外部服務的持續投資推動的，以支持加速的商業和整體公司建設。

The effective tax rate of 14% compared to 6% last year. As a reminder, we had a net operating loss carryforward of $2.3 billion at the end of 2020, which resulted in a nonrecurring benefit to the reported tax rate in 2021.

有效稅率為14%，而去年為6%。提醒一下，截至 2020 年底，我們的淨營業虧損結轉為 23 億美元，這為 2021 年報告的稅率帶來了非經常性收益。

After-tax net income decreased by 69% to $1 billion. Diluted EPS in Q3 2022 decreased by 67% to $2.53. As a result of our share buyback activities, the diluted weighted average share count reduced by 22 million shares to 412 million shares as of the end of Q3 2022 compared to 434 million shares the prior year.

稅後淨收入下降 69% 至 10 億美元。 2022 年第三季度的稀釋後每股收益下降 67% 至 2.53 美元。由於我們的股票回購活動，截至 2022 年第三季度末，稀釋加權平均股數減少了 2200 萬股，至 4.12 億股，而去年為 4.34 億股。

Turning now to the year-to-date financial results on Slide 26. Total product sales for the first 9 months of 2022 were $13.6 billion, an increase of 26% year-over-year. The growth was mainly attributable to a favorable customer mix and higher manufacturing capacity to fulfill customer demand for the first half of 2022 compared to the first half of 2021. Cost of sales was 26% of product sales compared to 16% of product sales last year. The increase was driven by substantial demand reduction from COVAX, as mentioned in our Q2 earnings call, a shift in demand to our Omicron-targeting COVID-19 bivalent boosters and costs associated with surplus production capacity.

現在轉向幻燈片 26 的年初至今財務業績。2022 年前 9 個月的產品總銷售額為 136 億美元，同比增長 26%。與 2021 年上半年相比，該增長主要歸因於有利的客戶組合和更高的製造能力以滿足 2022 年上半年的客戶需求。銷售成本佔產品銷售額的 26%，而去年佔產品銷售額的 16% .正如我們在第二季度財報電話會議中所提到的，這一增長是由於 COVAX 的需求大幅減少、需求轉向我們以 Omicron 為目標的 COVID-19二價助推器以及與產能過剩相關的成本。

After-tax net income was $6.9 billion, a decrease of 6% versus prior year. The decrease in net income was primarily due to higher cost of sales, higher other operating expenses and a higher tax rate. Diluted EPS decreased by 3% to $16.46.

稅後淨收入為 69 億美元，較上年下降 6%。淨收入減少主要是由於銷售成本增加、其他經營費用增加和稅率增加所致。稀釋後每股收益下降 3% 至 16.46 美元。

Turning to cash and cash deposits on Slide 27. We ended Q3 2022 with cash and investments of $17 billion compared to $18.1 billion at the end of the second quarter. The decrease reflects the share buyback in Q3 of $1 billion and a federal tax payment of $0.8 billion. The ending balance of cash deposits for future product supply at the end of the quarter was $3.8 billion.

轉向幻燈片 27 上的現金和現金存款。截至 2022 年第三季度，我們的現金和投資為 170 億美元，而第二季度末為 181 億美元。減少反映了第三季度 10 億美元的股票回購和 8 億美元的聯邦稅款。本季度末用於未來產品供應的現金存款餘額為 38 億美元。

Now turning to Slide 28. Our capital allocation priorities remain unchanged. Our top investment priority has been and will continue to be reinvesting in the base business across multiple areas. R&D spending was $2.1 billion in the year-to-date September period, a 55% year-over-year increase. We continue to be excited about our mRNA platform and now have 48 development programs with multiple ongoing studies now in Phase III.

現在轉到幻燈片 28。我們的資本配置優先事項保持不變。我們的首要投資重點一直是並將繼續在多個領域對基礎業務進行再投資。 9 月份至今的研發支出為 21 億美元，同比增長 55%。我們繼續對我們的 mRNA 平台感到興奮，現在有 48 個開發項目，多項正在進行的研究正處於 III 期。

We increased our year-to-date capital expenditures by 88% year-over-year to $308 million as we expand our manufacturing footprint. We also continue to invest in our commercial and digital capabilities, as well as the overall company build-out. Our second investment priority is to seek attractive external investments and collaboration opportunities to further expand the reach of Moderna's technologies and capabilities.

隨著我們擴大製造足跡，我們年初至今的資本支出同比增長 88% 至 3.08 億美元。我們還繼續投資於我們的商業和數字能力，以及整個公司的建設。我們的第二個投資重點是尋求有吸引力的外部投資和合作機會，以進一步擴大 Moderna 的技術和能力範圍。

We are considering attractive opportunities that enable and complement our platform and take a disciplined approach in evaluating potential outside investments. We are in multiple active discussions regarding additional external collaboration opportunities.

我們正在考慮具有吸引力的機會，以支持和補充我們的平台，並採取嚴格的方法評估潛在的外部投資。我們正在就額外的外部合作機會進行多次積極討論。

Then after evaluating internal and external investment opportunities, we then assess additional usage of cash. In the third quarter of 2022, we repurchased 7 million shares for $1 billion. Year-to-date through September 30, we repurchased 20 million shares for $2.9 billion. In October, we completed the $3 billion authorization approved in February 2022 and began to utilize the additional $3 billion August authorization.

然後在評估內部和外部投資機會後，我們評估現金的額外使用情況。 2022 年第三季度，我們以 10 億美元回購了 700 萬股股票。年初至今，截至 9 月 30 日，我們以 29 億美元回購了 2000 萬股股票。 10 月，我們完成了 2022 年 2 月批准的 30 億美元授權，並開始使用 8 月額外的 30 億美元授權。

Now let's turn to our 2022 updated financial framework on Slide 29. We now expect delivery in 2022 against signed advanced purchase agreements of $18 billion to $19 billion, reflecting deferrals of $2 billion to $3 billion into 2023 due to short-term supply chain constraints. This total includes expected negative foreign exchange impacts compared to the contract value at signing, which we estimate to be approximately 1.5% of sales for the full-year 2022, assuming current exchange rates remain through the year-end. Our total cost of sales includes the cost of goods manufactured, third-party royalties as well as logistics and warehousing costs. We now expect our full-year 2022 reported cost of sales to be in the 26 to 28 percentage range, driven by the previously mentioned cost incurred year-to-date, a range on our Q4 volume and potentially further charges due to product updates.

現在讓我們轉向幻燈片 29 上 2022 年更新的財務框架。我們現在預計 2022 年交付，而簽署的預購協議為 180 億美元至 190 億美元，這反映出由於短期供應鏈限制，將 20 億美元至 30 億美元推遲到 2023 年。這一總額包括與簽約時的合同價值相比的預期負面外匯影響，假設當前匯率到年底保持不變，我們估計約為 2022 年全年銷售額的 1.5%。我們的總銷售成本包括商品製造成本、第三方特許權使用費以及物流和倉儲成本。我們現在預計我們的 2022 年全年報告的銷售成本將在 26% 到 28% 的範圍內，這主要是由於前面提到的年初至今發生的成本、我們第四季度的銷量範圍以及由於產品更新而可能產生的進一步費用。

For R&D and SG&A, we continue to expect full-year expenses to be approximately $4 billion, driven by our maturing development portfolio and the global scale-up of our company. Based on current tax laws, we continue to expect our 2022 effective tax rate to be in the low to mid-teens as a result of benefits from the foreign-derived intangible income driven by our international business mix and stock-based compensation deduction.

對於研發和 SG&A，我們繼續預計全年支出約為 40 億美元，這得益於我們成熟的開發組合和我們公司的全球規模擴大。根據現行稅法，我們繼續預計我們 2022 年的有效稅率將在 10 至 10 歲左右，這是由於我們的國際業務組合和基於股票的薪酬扣除所驅動的外國無形收入帶來的好處。

Finally, regarding capital expenditures, we now expect capital expenditures to be approximately $0.5 billion, slightly below the previous range of $0.6 billion to $0.8 billion driven by the timing of project completion. This concludes my remarks concerning the financial performance, and I will turn the call back over to Stéphane.

最後，關於資本支出，我們現在預計資本支出約為 5 億美元，略低於之前受項目完成時間驅動的 6 億美元至 8 億美元的範圍。我對財務業績的評論到此結束，我將把電話轉回給 Stéphane。

Thank you, Jamie, Arpa and Stephen for this update. Before opening to Q&A, I just want to review some of the key priorities as we close out this year and look into 2023. For the remainder of the year, we'll continue to focus on delivering our updated Omicron boosters and drive 2022 sales. We're already working on 2023 sales contract in Europe, Japan and U.S. from afar around the world. Arpa and our team are also setting up with the U.S. team and scaling it so that we can go private in the U.S. market in 2023.

感謝 Jamie、Arpa 和 Stephen 的這次更新。在開始問答之前，我只想回顧一下今年結束並展望 2023 年的一些關鍵優先事項。在今年剩餘的時間裡，我們將繼續專注於提供更新的 Omicron 助推器並推動 2022 年的銷售。我們已經在世界各地為歐洲、日本和美國製定 2023 年的銷售合同。 Arpa 和我們的團隊也在與美國團隊建立並擴大規模，以便我們可以在 2023 年在美國市場私有化。

We continue to execute on our pipeline. We look forward to be able to present when we have it, the Phase II data of PCV expected before the end of the year. The team has done a great job to continue to enroll our Phase III study for flu and RSV and CMV and I'm excited to see the advancement of our rare disease programs.

我們繼續在我們的管道上執行。我們期待能夠在我們擁有它時展示PCV的II期數據，預計在今年年底之前。該團隊在繼續註冊我們針對流感、RSV 和 CMV 的 III 期研究方面做得非常出色，我很高興看到我們的罕見病項目取得進展。

Looking to next year, Arpa and the team and the entire organization, including manufacturing, is preparing for multiple vaccine launches in the year including commercial COVID market as well as potential for our therapic programs to move very quickly in Phase III.

展望明年，Arpa 和團隊以及包括製造在內的整個組織正在為今年推出多種疫苗做準備，包括商業 COVID 市場以及我們的治療計劃在第三階段快速推進的潛力。

And finally, we hope that many of you can join us next week for our first ESG Day on November 10. The virtual event will be available from our webcast. With this, we'll be happy to take your questions. Operator?

最後，我們希望你們中的許多人可以在下週加入我們，參加 11 月 10 日的第一個 ESG 日。虛擬活動將在我們的網絡廣播中提供。有了這個，我們很樂意回答您的問題。操作員？

(Operator Instructions) Our first question comes from Salveen Richter with Goldman Sachs.

（操作員說明）我們的第一個問題來自高盛的 Salveen Richter。

On pricing here for the COVID vaccine, Pfizer is guiding to a price of 110 to 130 in the private market. Is this in line with what your discussions thus far suggest? And when do you think the private market will emerge next year?

在此處為 COVID 疫苗定價時，輝瑞公司在私人市場上的定價為 110 至 130 美元。這與您迄今為止的討論所暗示的一致嗎？你認為私人市場明年什麼時候會出現？

And then a second question here. You were talking about some of the cost burden for next year with distribution costs and building out the commercial infrastructure around flu, RSV and trials. Could you just give us some directional color on the OpEx situation as we look to the forward?

然後是第二個問題。你談到了明年的一些成本負擔，包括分銷成本以及圍繞流感、RSV 和試驗建立商業基礎設施。當我們展望未來時，您能給我們一些關於 OpEx 情況的方向性顏色嗎？

So I can take the pricing question. So first, I'm not in a position to comment on competitor pricing. But as we think about our pricing as we evolve from a pandemic setting to an endemic setting, the real focus for us is on ensuring that our vaccines are priced based on the value that they provide to the health care system and reflect the cost-effectiveness guidelines that are set by public health authorities around the world. So for here, in the U.S., that would be ACIP.

所以我可以回答定價問題。因此，首先，我無法評論競爭對手的定價。但是，當我們考慮從大流行環境演變為地方病環境時的定價時，我們真正關注的是確保我們的疫苗定價基於它們為醫療保健系統提供的價值並反映成本效益由世界各地的公共衛生當局製定的指導方針。所以在這裡，在美國，那將是 ACIP。

I think it's important to note that some of the pricing guidance that has been released in the past is really at a gross level, and we do anticipate some discounting across different channels. Additionally, here in the United States as we evolve into the commercial setting, it's also important to remember that for all ACIP-recommended vaccines, there is a zero out-of-pocket cost for consumers. So from a consumer access perspective, we do expect that the pricing will not be a barrier to uptake.

我認為重要的是要注意過去發布的一些定價指南確實處於總體水平，我們確實預計不同渠道會出現一些折扣。此外，在美國，隨著我們進入商業環境，同樣重要的是要記住，對於所有 ACIP 推薦的疫苗，消費者的自付費用為零。因此，從消費者訪問的角度來看，我們確實希望定價不會成為採用的障礙。

And Salveen, maybe I'll take the cost part of that. So yes, our costs will change in an endemic mode. Number one, there are presentation, preferences moving more to prefilled syringe and single-dose vials that I think will be different year-over-year. We have to continue to invest in bivalent vaccines as well as Moderna will now pick up the distribution costs moving forward, particularly in the United States. And so yes, our cost profile will change and we'll come out and update in terms of what that means at a later date.

和 Salveen，也許我會承擔其中的一部分。所以，是的，我們的成本將在地方性模式下發生變化。第一，有介紹，偏好更多地轉向預裝注射器和單劑量小瓶，我認為這些會與去年同期相比有所不同。我們必須繼續投資於二價疫苗，而 Moderna 現在將承擔未來的分銷成本，尤其是在美國。所以是的，我們的成本概況將會改變，我們會在以後更新這意味著什麼。

(Operator Instructions) Our next question comes from Matthew Harrison with Morgan Stanley.

（操作員說明）我們的下一個問題來自摩根士丹利的 Matthew Harrison。

I was hoping to ask on PCV. Just given this is a Phase II study that's proof of concept, a p value greater than 0.05 could be considered a success in this study. So maybe you could just help us think about how you're thinking about a success in this study? And then just given that it's an open-label study, how much data is available to you internally?

我希望在PCV上問。鑑於這是一項概念驗證的 II 期研究，大於 0.05 的 p 值可被視為本研究的成功。所以也許你可以幫助我們想想你是如何看待這項研究的成功的？然後考慮到這是一項開放標籤研究，您可以在內部獲得多少數據？

Thanks, Matthew, for the question. So as you said, it's a Phase II study, but it's actually a quite sizable one. There's 150 patients, and they were randomized 2:1 so 100 patients have received the combination therapy and 50, the standard of care, which in this case is KEYTRUDA. That's actually by a sizable sample and does allow for us to look at efficacy.

謝謝，馬修，這個問題。所以正如你所說，這是一項 II 期研究，但它實際上是一個相當大的研究。有 150 名患者，他們以 2:1 的比例隨機分配，因此 100 名患者接受了聯合治療，50 名患者接受了標準治療，在這種情況下是 KEYTRUDA。這實際上是一個相當大的樣本，並且確實讓我們可以查看功效。

Now it is a Phase II study. And so we didn't prespecify a statistical threshold that we want to hit, but we are looking at hazard ratios across that, and we will get p values. I won't comment on a specific p value or hazard ratio at this time. It's premature to do so. But obviously, we are looking against standard of care to demonstrate a significant benefit over that standard of care. It's just important to note that the study wasn't powered for that at 150 participants. And so we will be looking to that hazard ratio and the p value as indicative.

現在是II期研究。所以我們沒有預先指定我們想要達到的統計閾值，但我們正在研究其中的風險比，我們將獲得 p 值。我目前不會評論具體的 p 值或風險比。這樣做還為時過早。但顯然，我們正在反對護理標準，以證明該護理標準具有顯著優勢。需要注意的是，這項研究並沒有針對 150 名參與者提供支持。因此，我們將把該風險比和 p 值視為指示性的。

And then depending upon the strength of that result, if it is, in fact, as you said, a p-value less than 0.05, and there's a very strong result, we will then make our subsequent decisions about how to proceed forward with development. Obviously, the better -- the stronger the benefit in terms of the hazard ratio and the lower the p value, the more we're going to move very quickly towards advancing that program.

然後根據該結果的強度，如果事實上，如您所說，p 值小於 0.05，並且結果非常強，那麼我們將就如何繼續開發做出後續決定.顯然，就風險比而言，收益越強，p 值越低，我們就越能快速推進該計劃。

Our next question comes from Edward Tenthoff with Piper Sandler.

我們的下一個問題來自 Edward Tenthoff 和 Piper Sandler。

Great. And congrats on all the progress. Appreciate all the detail on sort of the outlook, both for the COVID market and as we move forward. Questions back to my favorite topic, the orphan diseases. With this proof of concept in hand from the first programs, is there a desire to be expanding the pipeline similar to what you did with vaccines upon proof of concept with COVID?

偉大的。並祝賀所有進展。欣賞有關 COVID 市場和我們前進的前景的所有細節。問題回到我最喜歡的話題，孤兒疾病。有了第一個項目的概念證明，是否希望擴展管道，類似於您在 COVID 概念證明時對疫苗所做的那樣？

Thanks, Ed, for the question. And so I think the short version is, absolutely. In any of our modalities, whether they're cancer vaccines or infectious vaccines or now our orphan disease, where we believe we've achieved a technological proof of concept, where we've achieved what we wanted to do in patients, we look to rapidly expand the number of diseases and implications that we can bring forward that technology in. And in the case of orphan rare diseases, as we shared, we are extremely encouraged by the data across 2 different diseases using 2 different medicines that now suggest we have, obviously, acceptable safety and tolerability profile, which is of primary importance. But more importantly, for efficacy, we're starting to see really encouraging results in terms of biomarkers or even from a dynamic readout and potential of benefit for patients.

謝謝，埃德，這個問題。所以我認為短版絕對是。在我們的任何方式中，無論是癌症疫苗、傳染性疫苗還是現在我們的孤兒病，我們相信我們已經實現了概念的技術證明，我們已經實現了我們想要在患者身上做的事情，我們期待迅速擴大疾病的數量和我們可以提出該技術的影響。在罕見罕見病的情況下，正如我們所分享的，我們對使用兩種不同藥物的兩種不同疾病的數據感到非常鼓舞，這些數據現在表明我們已經，顯然，可接受的安全性和耐受性概況，這是最重要的。但更重要的是，就療效而言，我們開始在生物標誌物方面看到非常令人鼓舞的結果，甚至從動態讀數和對患者的潛在益處方面來看。

And so given the strength of those 2 pre prior results, we've actually moved quickly to expand our pipeline. We have a number of other programs that are already publicly disclosed and moving forward in clinical trials, some including M&A are already in clinical studies. And as I mentioned at our R&D Day, we're looking to substantially expand that pipeline of programs. And so we announced the OTC program as 1 instance of that just a month ago. But you can expect that we'll be adding substantially to that. Our goal will be to more than double that pipeline in the years ahead as we expand our investments in rare diseases on the back of that derisked clinical data.

因此，鑑於這兩個先前結果的優勢，我們實際上已經迅速採取行動來擴展我們的管道。我們還有許多其他計劃已經公開披露並在臨床試驗中取得進展，其中一些包括併購已經在臨床研究中。正如我在研發日提到的那樣，我們正在尋求大幅擴展該計劃管道。因此，我們在一個月前宣布了 OTC 計劃作為其中的一個實例。但是您可以期望我們會對此進行大量添加。我們的目標是在未來幾年將這一管道增加一倍以上，因為我們在這些低風險的臨床數據的支持下擴大了對罕見疾病的投資。

Our next question comes from Michael Yee with Jefferies.

我們的下一個問題來自 Jefferies 的 Michael Yee。

Maybe a question for Stephen. In RSV, we've had 2 players readout results. I think one is 80%, plus or minus; one, 66% plus or minus, depending on the endpoint. So I wanted to ask you how you view the bar in terms of being competitive and whether there's some differentiation opportunity for your RSV vaccine that could readout soon. So talk a little bit about that?

也許是斯蒂芬的問題。在 RSV 中，我們有 2 個玩家讀出結果。我認為一個是 80%，正負；一，66% 加減，取決於終點。所以我想問你，你如何看待競爭力的標準，以及你的 RSV 疫苗是否有一些差異化機會，很快就會公佈。那麼稍微談談這個？

And then just as a follow-up to PCV. Again, just to clarify, Merck had opted in. Can you comment on, I guess, the idea of the timing just before the data whether they had insufficient information or maybe just talk a little bit about the implications of that opt-in just before the data?

然後作為 PCV 的後續行動。再次澄清一下，默克公司選擇了加入。我猜你能否評論一下數據之前的時間點，無論他們是否有足夠的信息，或者只是談談之前選擇加入的影響數據？

Yes. Thank you for the question, Michael. So first on RSV, obviously, we're incredibly encouraged by the results that have been seen by other vaccines given our platform has previously demonstrated its potential in COVID specifically, in respiratory vaccines. We think it bodes well for us in terms of that study. There's a bar that's been established in terms of severe disease, as you referenced, in the 80% range. We are looking at 3 symptom or "severe disease."

是的。謝謝你的問題，邁克爾。因此，首先在 RSV 上，顯然，我們對其他疫苗所看到的結果感到非常鼓舞，因為我們的平台之前已經證明了它在 COVID 中的潛力，特別是在呼吸道疫苗中。我們認為就該研究而言，這對我們來說是個好兆頭。正如您所提到的，在嚴重疾病方面已經建立了一個標準，在 80% 範圍內。我們正在研究 3 症狀或“嚴重疾病”。

It's hard to compare between the studies. They're not conducted at the exact same time, and they always have exactly the same definition, as you know. But we would absolutely hope and expect that the type of efficacy we're going to see against severe disease will be on par with, and I would even hope for better than what's been seen by others. It's certainly been the case with our platform technology compared to others in terms of COVID that we've been able to see those sorts of potential benefits.

很難在研究之間進行比較。如您所知，它們並非在完全相同的時間進行，並且它們始終具有完全相同的定義。但我們絕對希望並期待我們將看到的針對嚴重疾病的療效類型將與其他人看到的效果相當，我什至希望比其他人看到的效果更好。在 COVID 方面，與其他平台技術相比，我們的平台技術肯定是這種情況，我們已經能夠看到這些潛在的好處。

I'll also note that we've looked at titers, and we previously shared our titers as well as other companies have from their early clinical Phase I and Phase II results and we believe that the boosting of neutralizing RSV titers against both RSV-A and RSV-B that we were achieving was on par, you could always argue perhaps better or worse, but on par with what others had seen. So we're quite encouraged by that. And I think we're looking forward to the RSV efficacy results over this coming winter. Our bar for this is to be as good or better than others have been.

我還要指出，我們已經查看了滴度，我們之前分享了我們的滴度以及其他公司從其早期臨床 I 期和 II 期結果中獲得的滴度，我們相信中和 RSV 滴度對 RSV-A 的提高和我們達到的 RSV-B 相當，你總是可以爭論可能更好或更糟，但與其他人看到的一樣。所以我們對此感到非常鼓舞。我認為我們期待著即將到來的冬天的 RSV 療效結果。我們的標準是與其他人一樣好或更好。

In terms of PCV. Our -- in terms of PCV, Merck has opted in, as you said, and I know Matthew asked the question as well. So it is an open-label study, as we previously disclosed. And so we have been following events through that study, those that have received the cancer vaccine in combination with KEYTRUDA versus that have not. And as we've now passed the 1-year mark for a follow-up of the last patient to be randomized in that study, we now have at least a year of follow-up and then (technical difficulty) cases, 2-plus years of follow-up across those 2 different cohorts, those that received combo and those received standard of care, KEYTRUDA. That data was known to us and Merck.

在 PCV 方面。正如你所說，就 PCV 而言，我們的默克公司選擇了加入，我知道 Matthew 也提出了這個問題。因此，正如我們之前披露的那樣，這是一項開放標籤研究。因此，我們一直在通過該研究跟踪事件，那些接受癌症疫苗與 KEYTRUDA 聯合治療的人與未接受的人。由於我們現在已經過了 1 年的時間，對最後一位在該研究中隨機分組的患者進行隨訪，我們現在至少有一年的隨訪時間，然後（技術難度）病例，2 多對這兩個不同的隊列進行了多年的隨訪，那些接受組合治療的和接受標準護理的，KEYTRUDA。我們和默克都知道這些數據。

But it's important to note, that's an ongoing uncleaned and not primary analysis. And so while it is open label, the correct thing to do at this point now is begin the closing process, get all of the scans, review all of the data associated with the clinical trials, make sure nothing was missed. And in that cleaning process, then finalize that database and conduct the primary analysis of the study, which is to evaluate the hazard ratio and the statistical significance of that hazard ratio between the 2 arms. That's actually the process we're undergoing right now.

但重要的是要注意，這是一個持續的未清理而不是主要分析。因此，雖然它是開放標籤，但此時正確的做法是開始關閉過程，獲取所有掃描，查看與臨床試驗相關的所有數據，確保沒有遺漏任何內容。然後在清理過程中，最終確定該數據庫並對研究進行初步分析，即評估風險比和該風險比在 2 組之間的統計顯著性。這實際上就是我們現在正在經歷的過程。

And it's important that before we make a decision on whether that data is positive or negative and the strength of that positivity, how quickly we move forward per Matthew's question into whatever the next data developments are, that we conduct all of the right diligence on those datasets. And that's the work that's ongoing right now. So while Merck made their opt-in decision, which was really more calendar and contract-driven, based on, obviously, having access to that open label information, the really important analysis, the primary analysis, the one on which we will base our decisions of what to do next as well regulators and others is the one that we're trying to conduct right now and is not yet completed, but we do expect that result in this quarter.

重要的是，在我們決定這些數據是正面還是負面以及這種積極性的強度之前，根據 Matthew 的問題，我們以多快的速度推進到下一個數據的發展，我們對這些數據進行所有正確的盡職調查數據集。這就是目前正在進行的工作。因此，雖然默克公司做出了他們的選擇加入決定，這實際上更多是日曆和合同驅動的，但顯然是基於可以訪問該開放標籤信息，真正重要的分析，主要分析，我們將以此為基礎的分析關於下一步做什麼以及監管機構和其他人的決定是我們現在正在嘗試進行的決定，但尚未完成，但我們確實希望在本季度取得結果。

(Operator Instructions) Our next question comes from Gena Wang with Barclays.

（操作員說明）我們的下一個問題來自巴克萊銀行的 Gena Wang。

Steve, maybe just follow-up with your comment on Merck. I just want to confirm that Merck does see the open-label data for the recurrence-free survival rate? And then also wanted to confirm that the control on the P1 model that will be in line with historical data that's in the low 7 days, that was the rate. And also, how would you share the data for the PCV Phase II data?

史蒂夫，也許只是跟進你對默克的評論。我只是想確認默克公司確實看到了無復發生存率的開放標籤數據？然後還想確認對 P1 模型的控制將與歷史數據保持一致，即低 7 天，這就是比率。此外，您將如何共享 PCV II 期數據的數據？

Another question is regarding Slide 19, the global COVID market opportunity. Since we expect significant increase in price in the U.S., what is your expectation for the ex-U.S. price change across major markets since you're giving like $20 to $40 price range?

另一個問題是關於幻燈片 19，即全球 COVID 市場機會。由於我們預計美國價格將大幅上漲，您對美國以外地區的預期是什麼？主要市場的價格變化，因為你給出了 20 到 40 美元的價格範圍？

Gena, thanks for that question. So again, it was not a continuous dataset. It was an open-label study. And so per our agreement with Merck, they had the right to know what do we know about the program at the point in which they were -- had to make their decision about whether to opt in or not. And so of course, what we did is we provided them the access to the data of the study at that point in time. And as you all have noted, they elected to opt in to that program, and we are encouraged by that decision on their part.

Gena，謝謝你的問題。再說一次，它不是一個連續的數據集。這是一項開放標籤研究。因此，根據我們與默克公司達成的協議，他們有權知道我們在他們所處的那個點上對該計劃了解多少——必須就是否選擇加入做出決定。因此，當然，我們所做的是我們在那個時間點為他們提供了對研究數據的訪問權限。正如你們都注意到的那樣，他們選擇加入該計劃，我們對他們的這一決定感到鼓舞。

They obviously do have a tremendous amount of experience. And so in terms of the control arm, you obviously have the KEYNOTE-054 study, which is their prior registrational studies. They have experience of what to expect in a control arm. And I think you can infer whatever you like from their decision to say that they believe it's worth opting into that program and proceeding to the primary analysis that we're conducting right now. We will obviously be able to compare the control arm, that 50 patients who just received KEYTRUDA as standard of care against the registrational studies that those are done and actually the many years of patient experience that companies like Merck and others have, just to be confident that, in fact, if we are seeing a difference between -- we are seeing a hazard ratio of difference that it's not a difference in terms of that control arm, which will bode well because, again, patients were randomized in this study.

他們顯然確實擁有豐富的經驗。因此，就控制臂而言，您顯然有 KEYNOTE-054 研究，這是他們之前的註冊研究。他們對控制臂的期望有經驗。而且我認為您可以從他們的決定中推斷出您喜歡的任何內容，即他們認為值得選擇該計劃並繼續進行我們現在正在進行的主要分析。我們顯然可以將對照組，即剛剛接受 KEYTRUDA 作為護理標準的 50 名患者與那些已經完成的註冊研究以及默克和其他公司等公司擁有的多年患者經驗進行比較，只是為了自信事實上，如果我們看到兩者之間的差異 - 我們看到差異的風險比，它不是那個控制臂的差異，這將是一個好兆頭，因為在這項研究中，患者再次被隨機分配。

Now in terms of the data we'll have in share, at this point, all we'd expect to share this quarter, once we've completed the analysis, the primary analysis on efficacy in this study, is just the top line data in terms of PCV, which, as I mentioned previously, is looking at the hazard ratio and then the characterization statistically of that. In subsequent and appropriate for, including meetings and otherwise, we will look to then share the fuller dataset over time.

現在就我們將共享的數據而言，在這一點上，我們希望在本季度共享的所有數據，一旦我們完成分析，本研究中對功效的主要分析，只是頂線數據就 PCV 而言，正如我之前提到的，它正在研究風險比，然後是對其進行統計表徵。在隨後和適當的情況下，包括會議等，我們將期待隨著時間的推移共享更完整的數據集。

And then I can take the pricing question. Your question was primarily around ex-U.S. pricing and our expectations. A couple of factors are coming into play here. The first is the timing of where and how quickly, ex-U.S. markets are going to be shifting from more of a central procurement pandemic setting to an endemic setting. So we are looking at how different regions and countries are going to be shifting back towards a more endemic or a commercial approach. When we get to that position, we will be, again, pricing the vaccine according to the value that it provides in different health care systems around the world. And again, following established systems around cost effectiveness guidelines based on the country regulations and the public health authority guidance.

然後我可以回答定價問題。你的問題主要是關於前美國的。定價和我們的期望。有幾個因素在這裡起作用。首先是美國以外的地點和速度的時間。市場將從更多的集中採購大流行環境轉變為地方性環境。因此，我們正在研究不同地區和國家將如何轉向更流行或商業化的方法。當我們到達那個位置時，我們將再次根據疫苗在全球不同醫療保健系統中提供的價值來定價。再次，遵循基於國家法規和公共衛生當局指導的成本效益指南的既定係統。

The overall global average price, we do anticipate will be largely driven by the regional mix. So it is hard to predict what that price will end up being. But we'll continue to share more as we see evolving demand as well as evolving pricing.

我們確實預計，全球整體平均價格將在很大程度上受到區域組合的推動。所以很難預測這個價格最終會是多少。但隨著我們看到不斷變化的需求和不斷變化的定價，我們將繼續分享更多信息。

Our next question comes from Tara Bancroft with Cowen.

我們的下一個問題來自 Tara Bancroft 和 Cowen。

So is it fair to say that the 2023 signed APAs of the $4.5 billion to $5.5 billion is the floor? And what minimum revenue do you think could be added from the geographies that you're expecting contracts from? And related to this then, to what extent does it include sales in the key markets that were mentioned in the press release, like, for example, does it include the option from the latest U.S. agreement?

那麼可以公平地說，2023 年簽署的 45 億至 55 億美元的 APA 是最低價嗎？您認為可以從您期望簽訂合同的地區增加多少最低收入？與此相關的是，它在多大程度上包括新聞稿中提到的關鍵市場的銷售，例如，它是否包括最新美國協議中的選項？

Thank you for the question. So the $4.5 billion to $5.5 billion is the floor sales that we anticipate in 2023 as we already have signed APAs as well as deferrals from 2022 into '23. This number does not include options from the U.S. government and we do anticipate additional sales coming from key markets such as the U.S., EU, Japan, Australia as well as regional sales in Latin America, Asia Pacific, Middle East and COVAX. So again, to answer your question specifically, this is what we anticipate to be the floor but still unknown in terms of the total opportunity as we evolve, particularly in the U.S. market into a commercial setting.

感謝你的提問。因此，45 億至 55 億美元是我們預計 2023 年的場內銷售額，因為我們已經簽署了 APA 以及從 2022 年推遲到 23 年。這個數字不包括美國政府的選項，我們確實預計來自美國、歐盟、日本、澳大利亞等主要市場的額外銷售以及拉丁美洲、亞太地區、中東和 COVAX 的區域銷售。因此，再次具體回答您的問題，這是我們預期的底線，但在我們發展的總機會方面仍然未知，特別是在美國市場進入商業環境。

(Operator Instructions) Our next question comes from Jessica Fye with JPMorgan.

（操作員說明）我們的下一個問題來自摩根大通的 Jessica Fye。

Are the short-term supply constraints mentioned the reason for delivery delays resolved at this point? How does bivalent booster uptake so far this fall compared to your expectations? And as it relates to China's potential orders of Western mRNA vaccines, what's your level of optimism that, that could come to fruition within some reasonable time lines over the next year or so?

提到的短期供應限制導致交貨延遲的原因在這一點上得到了解決嗎？與您的預期相比，今年秋天到目前為止二價增強劑的吸收情況如何？由於這與中國可能訂購的西方 mRNA 疫苗有關，您對在未來一年左右的合理時間範圍內實現這一目標的樂觀程度如何？

Sure. So it's Stéphane. I'm going to take the first question on supply, and then I'll turn to Arpa for the commercial PCUs. As I shared in my remarks, we actually have to deal with very complex third quarter from a manufacturing standpoint, not launching one product but 2, doing this kind of in a record times, as you are aware. We are gearing from this at the end of June that they wanted to be 5 products for the U.S. And that product was available in pharmacies all the weekend. And the shift from 10 dose per vial, which is what we sold with 1273. And for the first time, selling 5 dose per vial so basically doubling the number of vials needed or the same number of doses.

當然。所以是斯特凡。我將回答第一個關於供應的問題，然後我將向 Arpa 尋求商業 PCU。正如我在講話中所分享的，我們實際上必須從製造的角度處理非常複雜的第三季度，不是推出一種產品而是推出兩種產品，正如你所知，在創紀錄的時間內完成這種工作。我們正在為此在 6 月底準備好，他們希望成為美國的 5 種產品。該產品整個週末都可以在藥店買到。以及從每瓶 10 劑的轉變，這是我們用 1273 出售的。第一次，每瓶銷售 5 劑，因此基本上需要的小瓶數量或相同的劑量數量增加了一倍。

And so we've had quite a number of pain points with Fill/Finish manufacturers. We are working through a lot of those issues, a lot of stores, a lot are still being sold as we speak. There are many lessons to be learned that we are working on to put robust fixes for the end of the year but also that we are in a much better place for fall of 2023. Arpa?

因此，我們與填充/完成製造商有很多痛點。我們正在解決很多這樣的問題，很多商店，在我們說話的時候，很多東西仍在出售。有很多經驗教訓需要我們吸取，我們正在努力在年底進行強有力的修復，而且我們在 2023 年秋季處於一個更好的位置。Arpa？

Sure. So the first question around vaccine uptake. We are seeing some variability around the world in terms of vaccination rates with the best data thus far really coming from the U.S. market. As we look at 2022 vaccination uptake versus 2021, specifically for COVID boosters, we're actually tracking a similar pattern, and it's a little bit early to see what November, December and the rest of the fall and winter season will look like. But the early rates while in absolute terms are fairly low, they are tracking the trends that we expected compared to last year.

當然。所以第一個問題是關於疫苗的攝取。我們看到世界各地的疫苗接種率存在一些差異，迄今為止最好的數據確實來自美國市場。當我們比較 2022 年與 2021 年的疫苗接種率時，特別是對於 COVID 助推器，我們實際上正在追踪一個類似的模式，現在看看 11 月、12 月以及秋冬季節的其餘時間會是什麼樣子還為時過早。但早期利率雖然絕對值相當低，但與去年相比，它們正在追踪我們預期的趨勢。

Around the world, we are seeing some markets with very high uptake of explanation rates, really driven by public health authorities. And in other markets, we're still looking at sort of the dynamics that have played out this year with populations have recently gotten their fourth booster in the summertime and regulatory bodies recommending that they wait a few months before they get their fifth booster. So I think more to come as we continue to track around the world, but the early signs of uptake are encouraging.

在世界各地，我們看到一些市場的解釋率非常高，這實際上是由公共衛生當局推動的。在其他市場，我們仍在關註今年出現的動態，人口最近在夏季獲得了第四次助推器，監管機構建議他們等待幾個月才能獲得第五次助推器。因此，我認為隨著我們繼續在世界各地進行追踪，還會有更多進展，但早期的吸收跡象令人鼓舞。

Your last question on China. We continue to look at the opportunities in China. Nothing new to report here as of now, but it is certainly a key market of interest for us commercially.

你關於中國的最後一個問題。我們繼續關注中國的機遇。到目前為止，這裡沒有什麼新的報導，但它肯定是我們在商業上感興趣的一個關鍵市場。

(Operator Instructions) Our next question comes from Geoff Meacham Jeff with Bank of America.

（操作員說明）我們的下一個問題來自美國銀行的 Geoff Meacham Jeff。

Just had a couple. Just wanted to follow up on your last comment. You mentioned booster adoption has been mixed, depending on geographies. Is this something that you -- that Moderna expects to further invest in with regard to value boosters, additional follow-up and studies? That's the first question.

剛養了一對。只是想跟進您的最後評論。您提到助推器的採用情況參差不齊，具體取決於地理位置。這是你——Moderna 期望在價值提升、額外的跟進和研究方面進一步投資的東西嗎？這是第一個問題。

And the second one, maybe more for Stéphane, the balance sheet remains pretty strong. You guys have done some buybacks, but we haven't seen sort of a cluster of acquisitions or any sort of real capital allocation. Is -- where would M&A sort of fall in your priority list with uses of cash? And does that change as COVID continues to sort of wind down with regard to the revenue base '23 over '22 and maybe even more modest going forward?

第二個，也許對 Stéphane 來說更多，資產負債表仍然相當強勁。你們已經進行了一些回購，但我們還沒有看到類似的收購集群或任何形式的實際資本配置。是 - 併購在您使用現金的優先級列表中會落在哪裡？隨著 COVID 在 23 年和 22 年的收入基礎方面繼續下降，這種情況是否會發生變化，並且未來可能會更加溫和？

So to the first question on if we are investing in the vaccination rates, as I shared earlier today, the medical need continues to be clear for COVID booster vaccination, especially as we compare it to the hospitalizations and deaths compared to flu. So what we're really doing is partnering with governments and public health agencies to share the data that we have in terms of the ongoing medical need at a country level as well as the value of COVID booster vaccination in their populations. And it's this partnership with the public health authorities that's really driving increased urgency and action around vaccination. So that's our approach. So we believe public health authorities are in the best position to encourage a vaccination for their populations.

因此，對於第一個問題，正如我今天早些時候分享的那樣，我們是否正在對疫苗接種率進行投資，對於 COVID 加強疫苗接種的醫療需求仍然很明確，特別是當我們將其與住院和死亡人數與流感相比時。因此，我們真正要做的是與政府和公共衛生機構合作，分享我們在國家層面持續的醫療需求方面的數據，以及 COVID 加強疫苗在其人群中的價值。正是與公共衛生當局的這種夥伴關係真正推動了疫苗接種的緊迫性和行動。這就是我們的方法。因此，我們認為公共衛生當局最有能力鼓勵為其人口接種疫苗。

Thanks, Arpa. And on the balance sheet side, I mean our biggest strategy, as Jamie noted in his remarks, is unchanged. As you know, we are looking and have already signed deals in terms of technology licenses and also looking at M&A. As we've said before, we still focused on nucleic acid. We don't really think it's a good strategic use of our capital to buy small molecule asset or large molecule or cell therapy or else. So we really want the same nucleic acid.

謝謝，阿帕。在資產負債表方面，正如傑米在講話中指出的那樣，我的意思是我們最大的戰略沒有改變。如您所知，我們正在尋找並且已經簽署了技術許可方面的交易，並且還在考慮併購。正如我們之前所說，我們仍然專注於核酸。我們真的不認為將我們的資金用於購買小分子資產或大分子或細胞療法或其他方式的戰略性用途。所以我們真的想要同樣的核酸。

The bigger team is very active, as Jamie knows and his team knows. They are doing a lot of work where we're doing a lot of things. As I've said in the past, we'll remain disciplined in terms of understanding the risk have on the technology side, on the biology side, understanding value. We're here to create value, not to manage press release. But the team is very active. We are looking at diligence on a regular basis but not everything that we look at comes out to be something I think we can create a lot of value with. But we continue to look, and I would not be surprised if we continue to add partnerships in the months and quarters to come.

正如 Jamie 和他的團隊所知道的那樣，更大的團隊非常活躍。他們在做很多工作，而我們也在做很多事情。正如我過去所說，在理解技術方面、生物學方面的風險以及理解價值方面，我們將保持自律。我們在這裡創造價值，而不是管理新聞稿。但是團隊非常活躍。我們會定期進行盡職調查，但並非我們所看到的一切都成為我認為我們可以創造很多價值的東西。但我們會繼續關注，如果我們在未來幾個月和幾個季度繼續增加合作夥伴關係，我不會感到驚訝。

(Operator Instructions) Our next question comes from Eliana Merle with UBS.

（操作員說明）我們的下一個問題來自瑞銀的 Eliana Merle。

Just another one on RSV. In terms of thinking about mRNA as a vaccine modality in the context of RSV as we move beyond COVID vaccines, I guess how are you thinking about the potential for mRNA and potential advantages relative to other more traditional vaccine modalities in the context of RSV? And I guess, what we could learn from some of the upcoming readouts, both, I guess, with opportunity in RSV, but also what it could tell us about mRNA potential in vaccines relative to other modalities more broadly?

只是另一個關於 RSV 的。隨著我們超越 COVID 疫苗，在 RSV 的背景下將 mRNA 視為一種疫苗模式，我想您如何看待在 RSV 的背景下相對於其他更傳統的疫苗模式的 mRNA 的潛力和潛在優勢？而且我想，我們可以從即將發布的一些讀數中學到什麼，我想，無論是在 RSV 中的機會，還是它可以告訴我們相對於更廣泛的其他方式的疫苗中的 mRNA 潛力？

Great. Well, thank you for the question. So first, we have previously demonstrated with our platform in COVID and in fact, in some recent publications even in flu, that we generally see a really broad-based and balanced immune response. So we tend to see very high T cells and cell-mediated immunity and I would argue some of the highest, if not always the highest antibody neutralizing titers. And both of those are really important as you start talking about older adults and respiratory infections, which is probably why we've tended to see higher efficacy with the mRNA platform than other approaches in that high-risk population, including in COVID over the last couple of years.

偉大的。嗯，謝謝你的問題。因此，首先，我們之前已經在 COVID 中使用我們的平台證明了這一點，事實上，在最近的一些出版物中，甚至在流感中，我們通常會看到一個非常廣泛且平衡的免疫反應。因此，我們傾向於看到非常高的 T 細胞和細胞介導的免疫，我認為其中一些是最高的，如果不總是最高的抗體中和滴度。當您開始談論老年人和呼吸道感染時，這兩者都非常重要，這可能就是為什麼我們傾向於看到 mRNA 平台比其他方法在高危人群中的功效更高，包括在過去的 COVID 中許多年。

And so those features of the platform, the ability to generate really strong cell-mediated immunity, boost T cells, which are important for preventing severe disease but also pair that with achieving very high titers for a seasonal protection, where, again, you get high neutralizing titers, which provide a barrier to the amount of infection that you're going to get, which is really, really important for older adults because they're cell-mediated responses, they're innate immune system just isn't as strong, even with a great vaccine. And it's that combination that we think defines our advantage from a platform perspective and why we're so excited about developing a portfolio of respiratory vaccines across all the leading killers in that viral -- killers in that space, for older adults.

因此，該平台的這些功能，即產生非常強大的細胞介導免疫的能力，增強 T 細胞，這對於預防嚴重疾病很重要，但也與實現非常高滴度的季節性保護相結合，在這裡，你再次得到高中和滴度，為您將要獲得的感染量提供屏障，這對老年人來說非常非常重要，因為它們是細胞介導的反應，它們是先天免疫系統強大，即使有很好的疫苗。我們認為，正是這種組合從平台的角度定義了我們的優勢，以及為什麼我們如此興奮地為老年人開發針對該病毒所有主要殺手的呼吸道疫苗組合——該領域的殺手。

And RSV just fits right into that. As we all know, right now, there is a huge unmet need in that space. We're very pleased to have enrolled -- fully enrolled that Phase III study. And we're going to -- we're actually quite pleased with the titers and cell-mediated immunity that we saw in early development, some of which we presented publicly. So we're looking forward to that efficacy readout.

RSV 正好適合這一點。眾所周知，目前，該領域存在巨大的未滿足需求。我們很高興能夠註冊——完全註冊了 III 期研究。我們將——我們實際上對我們在早期開發中看到的滴度和細胞介導的免疫非常滿意，其中一些是我們公開展示的。因此，我們期待著功效讀數。

In terms of other approaches, let's also just celebrate that recombinant protein and viral vector and adjuvant approaches have all shown really exciting progress in the last 2 -- in the last really 1 year, 1.5 years across a range of companies. RSV has a huge unmet need. It will take many different approaches to have an impact there. And if anything, I think the success of others gives us optimism that our approach is going to also be successful, but there are likely going to be many different solutions to this for older populations.

在其他方法方面，讓我們也慶祝一下，重組蛋白和病毒載體以及佐劑方法在過去 2 年中都顯示出令人興奮的進展——在過去的 1 年、1.5 年中，一系列公司都取得了令人興奮的進展。 RSV 有一個巨大的未滿足需求。需要許多不同的方法才能在那裡產生影響。如果有的話，我認為其他人的成功讓我們樂觀地認為我們的方法也會成功，但對於老年人來說，可能會有許多不同的解決方案。

We do believe that our platform has an advantage. But given the success of the other vaccines and really, I think, quite encouraging efficacy results, it's important to note that there are many good successful options out there, and it may not always be possible to differentiate between them, but we hope to be in that first class.

我們確實相信我們的平台具有優勢。但考慮到其他疫苗的成功，而且我認為確實取得了相當令人鼓舞的療效結果，重要的是要注意，有很多成功的選擇，而且可能並不總是能夠區分它們，但我們希望能夠在第一堂課。

(Operator Instructions) Our next question comes from Joseph Stringer with Needham.

（操作員說明）我們的下一個問題來自 Joseph Stringer 和 Needham。

Just a clarification on the deferrals from the 2022 contracts, the $2 billion to $3 billion. Are those locked in signed APAs and they're just being deferred to '23? Or is there any optionality built into that?

只是對 2022 年合同延期的澄清，即 20 億至 30 億美元。那些被鎖定在簽署的 APA 中並且他們只是被推遲到 23 年？或者是否有任何內置的可選性？

And then the second question is just broader based pipeline. You're expanding pipeline, 48 programs, 35 clinical trials. But -- I was curious if you could comment on the relative mix of the pipeline, respiratory vaccines, immuno-oncology, rare disease, where it stands now and how you sort of see that evolving in that relative mix of the pipeline programs over time?

然後第二個問題只是基礎更廣泛的管道。你正在擴大管道、48 個項目、35 個臨床試驗。但是——我很好奇你能否評論管道、呼吸道疫苗、免疫腫瘤學、罕見病的相對組合，它現在的位置，以及你如何看待管道項目的相對組合隨著時間的推移而演變?

So maybe I'll take the first one quickly. So yes, those are locked in advanced purchase agreements for 2023, and so they're just shifting to the right from 2022.

所以也許我會很快拿下第一個。所以是的，這些都被鎖定在 2023 年的預購協議中，所以它們只是從 2022 年開始向右轉移。

Great. And on the broader question of the pipeline, as you mentioned, we've got 48 programs. Now, multiple Phase IIIs ongoing with some, we hope to be quite imminent readouts. As you look at it, right now, we are -- we have -- most of our late-stage pipeline is respiratory vaccine commercial, right? We have 4 programs there and we expect the flu and RSV data to come up quickly. And we will then move rapidly in respiratory into combination vaccines. And so we have 3 adult combination vaccines and clinical studies. We have 2 pediatric respiratory combination vaccines that are moving forward. And that you should expect to expand into very quickly, we would hope, registrational studies over the coming period, which will allow us to then build out what we hope will be the best respiratory portfolio, both from a monovalent vaccine perspective, but most importantly, from combinations against the viruses that matter in the different populations that we really want to protect, particularly older adults and the very young.

偉大的。正如你提到的，關於管道的更廣泛問題，我們有 48 個項目。現在，多個 III 期正在進行中，我們希望能夠很快得到讀數。正如你所看到的，現在，我們 - 我們擁有 - 我們的大部分後期管道都是呼吸道疫苗商業化，對嗎？我們在那裡有 4 個項目，我們預計流感和 RSV 數據會很快出現。然後我們將在呼吸系統領域迅速轉向聯合疫苗。因此，我們有 3 種成人聯合疫苗和臨床研究。我們有 2 種兒科呼吸道聯合疫苗正在向前發展。並且您應該期望在未來一段時間內迅速擴展到註冊研究，這將使我們能夠建立我們希望的最佳呼吸道產品組合，無論是從單價疫苗的角度來看，但最重要的是，來自針對我們真正想要保護的不同人群中重要的病毒的組合，特別是老年人和非常年輕的人。

So respiratory will be a growth area for us for the near term. But we will -- you'll start to see some diversification, again, talking about the late-stage. We already have a CMV Phase III program, which is up and running and enrolling, it has been. And you should expect this in our latent virus vaccines to add additional late-stage programs. We're quite passionate about Epstein-Barr virus as you all know, and we expect to move that in. And so you'll start to see some first diversification in terms of our latent virus portfolio, some of that's already happened with CMV.

因此，呼吸系統將是我們近期的一個增長領域。但我們會 - 你會開始看到一些多樣化，再次談論後期。我們已經有一個 CMV 第三階段計劃，它已經啟動、運行和註冊。您應該期望在我們的潛伏病毒疫苗中添加額外的後期程序。眾所周知，我們對 Epstein-Barr 病毒充滿熱情，我們希望將其引入。因此，就我們的潛伏病毒組合而言，您將開始看到一些首次多樣化，其中一些已經發生在 CMV 上。

The couple of things that will come quickly as well are we hope that the readout from our personalized cancer vaccine, therapeutic vaccine program. And it's really a therapeutic because we are preventing cancer from recurring, but we're intervening in somebody who's got that cancer already. And because of that, it really has a therapeutic profile to it as an intervention. And that therapeutic readout that we expect to have over the next month or so this quarter will trigger, if it's successful, moving into pivotal stage studies. And as we all know, immuno-oncology is obviously a competitive space. It's a space where there's still substantial need to improve upon the current IO therapy, and there are many different histologies and types of cancer in which it will make sense to develop a program if we show a benefit. So that expansion could happen very quickly and will be the large diversification into oncology in the therapeutic context outside of the vaccine space.

我們希望我們的個性化癌症疫苗和治療性疫苗計劃的讀數也會很快到來。這確實是一種治療方法，因為我們正在預防癌症復發，但我們正在干預已經患有癌症的人。正因為如此，它作為一種干預手段確實具有治療作用。我們預計在本季度下個月左右的治療讀數將觸發，如果它成功，進入關鍵階段研究。眾所周知，免疫腫瘤學顯然是一個競爭空間。這是一個仍然需要改進當前 IO 治療的空間，並且有許多不同的組織學和癌症類型，如果我們顯示出益處，開發一個程序將是有意義的。因此，這種擴張可能會很快發生，並將在疫苗領域之外的治療環境中實現腫瘤學的大規模多元化。

And then the last one is late -- is rare diseases, which we spoken about. We have a couple of programs that have already started to show some very encouraging results, both pharmacology and potential clinical readouts. And as soon as we decide on doses, for instance, the propionic acidemia program and get confident that we've got alignment with regulators on the path forward for that program, you should expect us to move into pivotal studies there as well. And then as I said and the answer to the prior question, that will not just be a one-off for us. Once we really believe we've got a modality, we will be bringing forward many programs in succession in parallel there.

然後最後一個遲到了——是我們談到的罕見疾病。我們有幾個項目已經開始顯示出一些非常令人鼓舞的結果，包括藥理學和潛在的臨床讀數。一旦我們決定劑量，例如，丙酸血症計劃並確信我們已經與監管機構在該計劃的前進道路上保持一致，您應該期望我們也進入那裡的關鍵研究。然後正如我所說的以及對上一個問題的回答，這對我們來說不僅僅是一次性的。一旦我們真正相信我們已經有了一種模式，我們將在那裡並行推出許多計劃。

And so as you look forward on how do we think about the diversification of the pipeline is a bigger question, it really is a question of time horizon. Right now, it's a lot of respiratory and latent. Very quickly though, we expect to be both expanding that respiratory and expanding our move in to therapeutics, particularly cancer and rare metabolic disease. And that could happen in quite short order based on upcoming clinical readouts.

因此，當您期待我們如何看待管道的多樣化是一個更大的問題時，這確實是一個時間範圍的問題。現在，它是很多呼吸和潛伏的。不過，很快，我們希望既能擴大呼吸系統，又能擴大我們在治療領域的發展，尤其是癌症和罕見的代謝疾病。根據即將到來的臨床讀數，這可能會在很短的時間內發生。

(Operator Instructions) Our next question comes from Mani Foroohar with SVB Securities.

（操作員說明）我們的下一個問題來自 SVB 證券的 Mani Foroohar。

This is Lili Nsongo on for Mani Foroohar. I just had a question related to volume to be expected. So I know that your volume prediction, you mentioned that you'd exclude 2023 based on because of the variability there. But I was wondering for 2023, how much of these volumes or revenues anticipate to be driven by the APAs? And also as you move to our more endemic model for [local-induction] use continue to anticipate APAs in the future?

這是 Mani Foroohar 的 Lili Nsongo。我只是有一個與預期數量有關的問題。所以我知道你的銷量預測，你提到你會排除 2023 年，因為那裡的可變性。但我想知道到 2023 年，這些數量或收入中有多少預計將由 APA 推動？並且當您轉向我們更流行的 [local-induction] 使用模型時，是否會繼續預測未來的 APA？

Sure. Thank you for that question. As I outlined in terms of the volume expectations for next year, outside of the signed APAs, we are looking at a number of variables that could impact the total volume. So in the long term, we do believe we should approach 500 million to 600 million volume comparable to the flu volumes that exist today. In 2023, there will be a range depending on the viral evolution, the ongoing medical need across different regions, where we see public health authorities coming out with recommendations as well as just a broader consumer appetite to vaccinate.

當然。謝謝你的問題。正如我就明年的銷量預期所概述的那樣，在簽署的 APA 之外，我們正在研究可能影響總銷量的一些變量。因此，從長遠來看，我們確實相信我們應該接近 5 億到 6 億的數量，與今天存在的流感數量相當。到 2023 年，範圍將取決於病毒的演變、不同地區持續的醫療需求，我們看到公共衛生當局提出建議以及更廣泛的消費者對疫苗接種的興趣。

So the reason for the sensitivity on the volume that I shared earlier is we still have a number of variables as we're continuing to transition into an endemic stage. And so in the short term, we don't have a clear picture of that total volume and what that could look like, but we do believe, from a medical perspective, over time, we should be approaching at least the same volumes as the flu market.

因此，我之前分享的對音量敏感的原因是，隨著我們繼續過渡到流行階段，我們仍然有許多變量。因此，在短期內，我們無法清楚地了解總量以及可能的情況，但我們確實相信，從醫學的角度來看，隨著時間的推移，我們應該至少接近與流感市場。

And I'm not showing any further questions at this time. I'd like to turn the call back over to Stéphane Bancel for any closing remarks.

我目前沒有提出任何進一步的問題。我想將電話轉回給 Stéphane Bancel，以聽取任何結束語。

Well, thank you, everybody, for joining the call today and for your thoughtful questions. We look forward to speaking to many hours to come -- days to come and also welcoming you next week for our first ESG Day. Have a great day. Bye.

好吧，謝謝大家今天加入電話會議並提出深思熟慮的問題。我們期待在未來的數小時內與您交談，並在下週歡迎您參加我們的第一個 ESG 日。祝你有美好的一天。再見。

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect, and have a wonderful day.

女士們，先生們，今天的演講到此結束。您現在可以斷開連接，度過美好的一天。