莫德納 (MRNA) 2020 Q2 法說會逐字稿

Good morning, and welcome to Moderna's conference call. (Operator Instructions) Please be advised that the call is being recorded. At this time, I'd like to turn the call over to Lavina Talukdar, Head of Investor Relations at Moderna. Please proceed.

早上好，歡迎參加 Moderna 的電話會議。 （操作員說明）請注意，通話正在錄音。現在，我想將電話轉給 Moderna 投資者關係主管 Lavina Talukdar。請繼續。

Thank you, operator. Good morning, everyone, and welcome to Moderna's Second Quarter 2020 Conference call to discuss financial results and business update. 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，接線員。大家早上好，歡迎參加 Moderna 2020 年第二季度電話會議，討論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 Stéphane Bancel, our Chief Executive Officer; Tal Zaks, our Chief Medical Officer; Stephen Hoge, our President; and David Meline, our Chief Financial Officer.

我們的首席執行官 Stéphane Bancel 出席了今天的電話會議； Tal Zaks，我們的首席醫療官；斯蒂芬·霍格，我們的總裁；以及我們的首席財務官 David Meline。

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。

I will now turn the call over to Stéphane.

我現在將把電話轉給 Stéphane。

Thank you, Lavina. Good morning or good afternoon, everyone. I hope all of you are in good health and remain safe. Thank you for joining our Q2 business update.

謝謝你，拉維娜。大家早上好或者下午好。我希望你們所有人都身體健康並保持安全。感謝您參與我們的第二季度業務更新。

We are committed to building mRNA as a new class of medicines, with Moderna positioned to remain the leader in this field. As you know, we believe our mRNA medicines have a potential to address large unmet medical needs and to treat diseases that are not addressable by recombinant protein or small molecules. Due to the platform nature of mRNA, we believe our mRNA medicines provide a higher probability of technical success to commercial launch and faster time lines to clinical trials and to the market relative to traditional medicines. We also believe that the manufacturing capital intensity of mRNA is materially lower than recombinant proteins, but our cost of manufacturing at commercial scale will be similar to small molecule injectables.

我們致力於將 mRNA 打造成一類新的藥物，Moderna 定位於保持該領域的領導者地位。如您所知，我們相信我們的 mRNA 藥物有潛力解決大量未滿足的醫療需求，並治療重組蛋白或小分子無法解決的疾病。由於 mRNA 的平台性質，我們相信，相對於傳統藥物，我們的 mRNA 藥物為商業上市提供了更高的技術成功概率，並為臨床試驗和市場提供了更快的時間。我們還認為，mRNA 的製造資本強度大大低於重組蛋白，但我們的商業規模製造成本將與小分子注射劑相似。

Let me start by summarizing the key achievement of the company in Q2 on Slide 4.

首先，我在幻燈片 4 上總結了公司第二季度的主要成就。

mRNA-1273, our COVID-19 vaccine candidate, saw the start of its Phase II, and the team focused on the Phase III design in preparation for a July start. We signed a strategic long-term partnership with Lonza towards significant manufacturing capacity to make mRNA and formulate it at large industrial scale to complement our Massachusetts manufacturing site capacity in the context of a pandemic. We started the technology transfer to Lonza in Q2. We raised $1.3 billion on May 18. And as communicated in our S-3, this capital was raised to enable us to scale up at risk our manufacturing capacity in anticipation of a potential approval for mRNA-1273. We started investing the proceeds for additional capital equipment at our Massachusetts plant as well as the Lonza plant in New Hampshire and in Switzerland, ordering raw materials at large-scale and hiring additional personnel to make mRNA-1273.

我們的 COVID-19 候選疫苗 mRNA-1273 已開始第二階段，團隊專注於第三階段設計，為 7 月份的啟動做準備。我們與 Lonza 簽署了長期戰略合作夥伴關係，以建立巨大的製造能力來生產 mRNA 並進行大規模工業化配製，以補充我們在大流行背景下馬薩諸塞州製造基地的能力。我們在第二季度開始向 Lonza 進行技術轉讓。我們於5 月18 日籌集了13 億美元。正如我們在S-3 中所傳達的那樣，籌集這筆資金是為了使我們能夠冒著風險擴大我們的生產能力，以應對mRNA-1273 可能獲得批准的情況。我們開始將所得款項投資於馬薩諸塞州工廠以及新罕布什爾州和瑞士的 Lonza 工廠的額外資本設備，大規模訂購原材料並僱用更多人員來生產 mRNA-1273。

In April, we finalized and announced an award from BARDA for up to $483 million for clinical development costs for mRNA-1273. An additional award was also announced last week for up to $472 million, given the increased size of a Phase III to 30,000 participants. The total award is now up to $955 million.

4 月份，我們敲定並宣布 BARDA 授予高達 4.83 億美元的 mRNA-1273 臨床開發費用。鑑於第三階段的參與者規模增加至 30,000 名，上週還宣布了一項高達 4.72 億美元的額外獎勵。目前獎金總額高達 9.55 億美元。

In a very difficult environment during the spring, given the many lockdowns across the U.S. due to COVID-19 outbreaks, our clinical team was able to continue to operate most of our clinical trials on schedule. And we remain on track to provide in Q3 the Phase II interim data for CMV vaccine candidate, mRNA-1647. The team continues to work relentlessly to start the Phase III study for CMV in 2021. We continue to believe that our CMV vaccine candidate's annual peak sales could be $2 billion to $5 billion. And like MRNA-1273, our COVID vaccine candidate, we own the global commercial rights of mRNA-1647, our CMV vaccine candidate.

在春季非常困難的環境中，由於 COVID-19 爆發，美國各地實施了多次封鎖，我們的臨床團隊能夠繼續按計劃進行大部分臨床試驗。我們仍有望在第三季度提供 CMV 候選疫苗 mRNA-1647 的 II 期中期數據。該團隊將繼續不懈努力，爭取在 2021 年啟動 CMV III 期研究。我們仍然相信，我們的 CMV 候選疫苗的年度峰值銷售額可能會達到 20 億至 50 億美元。與我們的新冠候選疫苗 mRNA-1273 一樣，我們擁有 CMV 候選疫苗 mRNA-1647 的全球商業權。

Q2 marked a new growth phase for our company as we started to build and hire our commercial team. This is a historic moment for those of us who have worked at the company for many years since it was a breakthrough research enterprise working with small animal models. And now we are building commercial.

第二季度標誌著我們公司進入了一個新的增長階段，我們開始組建和僱用我們的商業團隊。對於我們這些在該公司工作多年的人來說，這是一個歷史性的時刻，因為它是一家從事小動物模型研究的突破性研究企業。現在我們正在建設商業。

In Q2, the team started discussions with several countries around the world about potential supply agreements for mRNA-1273. We saw our first deferred revenues booked in Q2 on the balance sheet for $75 million of cash receipt from deposit for first potential supply of mRNA-1273. As of July 27, we have received approximately $400 million of cash deposit.

第二季度，該團隊開始與世界多個國家討論 mRNA-1273 的潛在供應協議。我們在第二季度在資產負債表上看到了我們的第一筆遞延收入，其中 7500 萬美元是從 mRNA-1273 的第一批潛在供應保證金中獲得的現金收入。截至7月27日，我們已收到約4億美元的現金存款。

For today's call, we will cover 3 main topics. First, Tal will review and update you on our clinical programs and share some new clinical data on our CMV and Zika vaccine candidates, then Stephen and I will share with you our value framework for vaccine COVID-19 candidate and our approach for delivering value during the pandemic. Finally, David will take you through the second quarter financials.

在今天的電話會議中，我們將討論 3 個主要主題。首先，Tal 將審查並更新我們的臨床計劃，並分享有關我們的 CMV 和 Zika 候選疫苗的一些新臨床數據，然後 Stephen 和我將與您分享我們的 COVID-19 候選疫苗的價值框架以及我們在大流行。最後，大衛將帶您了解第二季度的財務狀況。

Let me now turn the call to Tal.

現在讓我把電話轉給塔爾。

Thank you, Stéphane, and good morning, everyone.

謝謝你，斯特凡，大家早上好。

Let me start with our prophylactic vaccines portfolio. A quick overview of the programs is on Slide 7.

讓我從我們的預防性疫苗產品組合開始。幻燈片 7 提供了這些程序的快速概述。

mRNA-1273, our vaccine against COVID-19, has made very significant progress. The interim results of the Phase I trial have now been published in the New England Journal of Medicine. The Phase II trial was fully enrolled. And importantly, we recently started the Phase III trial of 30,000 volunteers in the U.S. Our CMV Phase II dose confirmation study remains on track for interim data in the third quarter of this year and the Phase III trial is expected to begin in next year. The Phase I trial for Zika is fully enrolled, and I'll share some data from the 100 and 200 and 50-microgram dose cohorts shortly while we're preparing for Phase II. Our Phase Ib HD escalation study with our combination hMPV/PIV3 vaccine remains on pause with enrollment suspended due to COVID-19 disruptions. And finally, the Phase I study with mRNA-1172 against RSV, led by our partner, Merck, is ongoing.

我們針對 COVID-19 的疫苗 mRNA-1273 已取得非常重大的進展。 I期試驗的中期結果現已發表在《新英格蘭醫學雜誌》上。 II期試驗已全部入組。重要的是，我們最近在美國開始了對30,000 名志願者進行的III 期試驗。我們的CMV II 期劑量確認研究仍在按計劃進行，將在今年第三季度獲得中期數據，III 期試驗預計將於明年開始。 Zika 的 I 期試驗已全部入組，在我們為 II 期做準備時，我將很快分享 100、200 和 50 微克劑量組的一些數據。由於 COVID-19 中斷，我們使用 hMPV/PIV3 組合疫苗進行的 Ib 期 HD 升級研究仍處於暫停狀態，入組也暫停。最後，由我們的合作夥伴默克公司領導的針對 RSV 的 mRNA-1172 的 I 期研究正在進行中。

So it is new today, the additional data from our CMV and Zika Phase I programs. For CMV, these include 12-month immunogenicity data from dose cohorts 30, 90 and 180-microgram and the safety data from the 300-microgram dose cohort. For Zika, we have disclosed data from the 10 and 30-microgram cohorts. And today, I'll show you the safety and immunogenicity data for the 100 and 200 and 50-microgram dose groups.

所以今天是新的，來自我們的 CMV 和 Zika 第一階段項目的附加數據。對於 CMV，這些包括 30、90 和 180 微克劑量組的 12 個月免疫原性數據以及 300 微克劑量組的安全性數據。對於寨卡病毒，我們披露了 10 微克和 30 微克組的數據。今天，我將向您展示 100 微克、200 微克和 50 微克劑量組的安全性和免疫原性數據。

So starting with CMV. On Slide 9, you will see a table of the solicited adverse events after the third and final vaccination in the highest dose we tested, 300-microgram. The safety and reactogenicity data from this dose is despite side-by-side with the other lower dose cohorts from the trial. At the 300-microgram dose level, solicited adverse event reaction showed a trend towards increases with the higher dose and who are higher and seropositive. This is consistent with what we've seen in the other doses as we moved from 30 to 90 and 180 micrograms. The most commonly reported adverse events were pain at the injection site, headache, fatigue, myalgia and chills for seronegative participants, with fever and arthralgia as more common adverse events in seropositives. Importantly, at the 300-microgram dose, there continues to be no related serious adverse events reported and no unexpected safety findings.

所以從 CMV 開始。在幻燈片 9 上，您將看到一張表格，其中列出了在我們測試的最高劑量（300 微克）的第三次也是最後一次疫苗接種後引起的不良事件。儘管該劑量的安全性和反應原性數據與該試驗中其他較低劑量組的數據並列。在 300 微克劑量水平下，引起的不良事件反應呈隨劑量越高、劑量越高且血清反應呈陽性而增加的趨勢。這與我們從 30 微克增加到 90 微克和 180 微克時在其他劑量中看到的情況一致。最常見的不良事件是血清陰性參與者的注射部位疼痛、頭痛、疲勞、肌痛和發冷，而血清陽性參與者中更常見的不良事件是發燒和關節痛。重要的是，在 300 微克劑量下，仍然沒有報告相關的嚴重不良事件，也沒有意外的安全發現。

Moving to the 12-month immunogenicity data for the full 30, 90 and 180-microgram dose cohorts in the Phase I CMV trial, we're happy to report that 6 months after the last vaccination with mRNA-1647, we have durable neutralizing antibody responses out to the 12-months’ time frame.

轉向 I 期 CMV 試驗中完整 30、90 和 180 微克劑量組的 12 個月免疫原性數據，我們很高興地報告，在最後一次接種 mRNA-1647 後 6 個月，我們有了持久的中和抗體12 個月的期限內作出答复。

Slide 10 shows the data in the same format we reported previously. At the top part of the table, you see the geometric mean neutralizing antibody titers against epithelial cell infections or the pentamer at the 12-months mark as well as the fold increases above the seropositive benchmark of 5,917. At the 90 and 180-microgram doses, the fold increase in geometric mean titers above that seropositive benchmark were 3.6 and 3.9-fold higher, respectively. In the bottom of half of the table, figures for the geometric mean antibody titers against fibroblast infection or the GB antigen for the same doses can be seen. And the geometric mean titers against fibroblast cells in the 90 and 180-microgram were 0.7 and 0.9-fold seropositive benchmark level of 1,449.

幻燈片 10 顯示的數據格式與我們之前報告的格式相同。在表格的頂部，您可以看到 12 個月時針對上皮細胞感染或五聚體的幾何平均中和抗體滴度，以及高於血清陽性基準 5,917 的倍數增加。在 90 微克和 180 微克劑量下，幾何平均滴度高於血清陽性基準的倍數分別增加了 3.6 和 3.9 倍。在表的下半部分，可以看到相同劑量下抗成纖維細胞感染或GB抗原的幾何平均抗體滴度的數字。 90 微克和 180 微克的成纖維細胞幾何平均效價分別是血清陽性基準水平 1,449 的 0.7 和 0.9 倍。

Now on Slide 11 is the graphical representation of the geometric mean antibody titers against the epithelial cell infection relative to the seropositive benchmarks geometric mean titer. And the scale is a log scale. You can see the seronegative participants by the solid lines and the increase in neutralizing antibody titers for each of the doses after each vaccination. The 90 and 180-microgram doses are shown in solid blue and orange and they're well above the benchmark seropositive level at the 12-month mark. This is 6 months after the last vaccination. So the persistence of neutralizing antibodies is encouraging. Seropositives are represented by the dash lines. These participants entered the trial with neutralizing antibodies, as you can see from the start. And they also saw their neutralizing antibody levels further increase with each vaccination remaining above the geometric mean titer for neutralizing antibody levels to the 12-months mark.

現在幻燈片 11 是針對上皮細胞感染的幾何平均抗體滴度相對於血清陽性基準幾何平均滴度的圖形表示。刻度是對數刻度。您可以通過實線以及每次疫苗接種後每個劑量的中和抗體滴度的增加來查看血清陰性參與者。 90 微克和 180 微克劑量以純藍色和橙色顯示，遠高於 12 個月時的基準血清陽性水平。這是最後一次疫苗接種後 6 個月。因此，中和抗體的持續存在令人鼓舞。血清陽性由虛線表示。正如您從一開始就可以看到的那樣，這些參與者帶著中和抗體進入試驗。他們還發現，隨著每次疫苗接種保持在中和抗體水平幾何平均效價以上，直至 12 個月，他們的中和抗體水平進一步增加。

CMV is an important unmet need and we are encouraged and excited by these 12-months data. We're currently running the Phase II dose confirmation study where we're testing a narrow range of doses at the 50, 100 and 150-microgram, 252 seronegative [NCR] positive adults have been enrolled, and we remain on track for an interim readout in the third quarter of this year. We continue to plan for the Phase III trial in 2021, pending further regulatory interactions and feedback. The primary end point, as we had previously reported, is anticipated to be prevention of primary infection in seronegative women of child-bearing age, and we expect to include less than 8,000 participants in the U.S. and Europe.

CMV 是一項重要的未滿足需求，我們對這些 12 個月的數據感到鼓舞和興奮。我們目前正在進行 II 期劑量確認研究，我們正在測試 50、100 和 150 微克的狹窄劑量範圍，已招募了 252 名血清陰性 [NCR] 陽性成人，並且我們仍在按計劃進行臨時研究。今年第三季度的數據。我們繼續計劃 2021 年的 III 期試驗，等待進一步的監管互動和反饋。正如我們之前報導的，主要終點預計是預防血清陰性育齡婦女的原發感染，我們預計包括美國和歐洲的不到 8,000 名參與者。

Let me now move to mRNA-1893, our vaccine against the Zika virus, where we've seen additional data at the 100 and 250-microgram dose levels. Both of these dose levels were generally well tolerated, with a trend towards more observations of local erythema and swelling at the injection site with the higher dose levels and after the second vaccination. Consistent with what we've seen across our vaccine platform, there's a trend of more solicited systemic adverse events noted with 250-microgram dose levels, particularly after the second dose. There were no related serious adverse events. You can see some of the 30-microgram data have been updated from our Vaccine Day presentation back in April.

現在讓我談談 mRNA-1893，這是我們針對寨卡病毒的疫苗，我們已經看到了 100 微克和 250 微克劑量水平的更多數據。這兩種劑量水平通常都具有良好的耐受性，在較高劑量水平和第二次疫苗接種後，注射部位有更多觀察到局部紅斑和腫脹的趨勢。與我們在疫苗平台上看到的情況一致，250 微克劑量水平有出現更多系統性不良事件的趨勢，特別是在第二劑之後。沒有相關的嚴重不良事件。您可以看到一些 30 微克數據已從我們四月份的疫苗日演示中更新。

In terms of the immunogenicity response, both the 100 and 250-microgram dose level induced a strong neutralizing antibody response in both seropositive and seronegative participants. The table on the left-hand side focuses on the seronegative participants and the data for the 10 and 30-microgram cohorts have been previously shared. All seronegative participants in the 100-microgram dose cohorts here converted after the second vaccination, similar to that seen with a lower 30-microgram dose cohort, but now with higher geometric mean titers, as depicted graphically on the bottom. We did not see any further increase at the 250-microgram relative to the 100-microgram dose.

就免疫原性反應而言，100 微克和 250 微克劑量水平均在血清陽性和血清陰性參與者中誘導了強烈的中和抗體反應。左側的表格重點關注血清陰性參與者，10 微克和 30 微克隊列的數據之前已共享。 100 微克劑量組中的所有血清陰性參與者在第二次疫苗接種後都發生了轉變，與較低的30 微克劑量組中觀察到的情況類似，但現在具有更高的幾何平均滴度，如下圖所示。相對於 100 微克劑量，我們沒有看到 250 微克劑量有任何進一步增加。

On this page, you can see the data for participants with pre-existing flavivirus immunity or the seropositives where mRNA-1893 was still able to mount to Zika-specific neutralizing antibody response. Here, the first vaccination is comparable to a booster response. And the response was similar between all those levels, although, of course, I would note that these are very small numbers. We are reviewing the data and we'll make a dose selection decisions in preparation for the Phase II and this program continues to be supported by BARDA.

在此頁面上，您可以查看預先存在黃病毒免疫力的參與者或 mRNA-1893 仍能夠產生寨卡特異性中和抗體反應的血清陽性參與者的數據。在這裡，第一次疫苗接種相當於加強反應。所有這些級別之間的反應都是相似的，儘管我當然會注意到這些數字非常小。我們正在審查數據，並將做出劑量選擇決定，為第二階段做準備，該計劃將繼續得到 BARDA 的支持。

So let me quickly review at a high level the data generated to date with mRNA-1273, our vaccine against COVID-19. The Phase I clinical data we published in the New England Journal showed that 100% of the participants vaccinated generated neutralizing antibodies, and the geometric mean titer level at day 43 were 4.1-fold higher than those seen in convalescent sera from 3 representative COVID-19 patients. As published recently in the New England Journal of Medicine, in the nonhuman primate vaccination with the 2 dose regimen of mRNA-1273 led to rapid protection against infection in both the lungs in those of the animals. Finally, a preprint from a mouse challenge model had showed consistent protection in the lungs and noses of those animals as well. And this morning, we're happy to hear that NEJM published this study and is available online today.

因此，讓我快速回顧一下迄今為止我們針對 COVID-19 的疫苗 mRNA-1273 生成的數據。我們在《新英格蘭雜誌》上發表的I 期臨床數據顯示，100% 的接種者產生了中和抗體，第43 天的幾何平均滴度水平比3 種代表性COVID-19 恢復期血清中的幾何平均滴度水平高4.1 倍患者。正如最近在《新英格蘭醫學雜誌》上發表的那樣，在非人類靈長類動物疫苗接種中，使用 2 劑 mRNA-1273 方案可快速保護動物雙肺免受感染。最後，小鼠挑戰模型的預印本也顯示出對這些動物的肺部和鼻子的一致保護。今天早上，我們很高興聽到 NEJM 發表了這項研究，並可在今天在線獲取。

So we've been able to show protection against the viral replication in every species we've tested so far, and the levels of neutralizing antibodies that correlated this protection are roughly similar to those we achieved in humans in Phase I. So we look forward to the data readout expected in the coming months, which will include the older and elderly cohorts in the Phase I, the safety and immunogenicity data from the Phase II and the potential for interim safety and efficacy analysis from the Phase III COVID trial.

因此，我們已經能夠在迄今為止測試的每個物種中顯示出針對病毒複製的保護作用，並且與這種保護作用相關的中和抗體水平與我們在第一階段中在人類中實現的水平大致相似。所以我們期待預計未來幾個月將公佈數據，其中將包括第一階段的老年人和老年隊列、第二階段的安全性和免疫原性數據以及第三階段新冠肺炎試驗的中期安全性和有效性分析的潛力。

Let me now quickly review our other clinical programs. In the systemic secreted and cell surface therapeutics, I'm happy to report that the additional 2 cohorts in the Phase I trial for mRNA-1944 have recently completed enrollment. As a reminder, in this program, the mRNA-1944 encodes for an IgG antibody against the chikungunya virus. The 2 additional cohorts are testing in IV infusion of mRNA-1944 at the high dose of 0.6 mg per kg with steroid premedication as well as 2 doses of 0.3 mg per kg without steroid premedication given a week apart. The randomized Phase II trial of our personalized cancer vaccine in combination with KEYTRUDA versus KEYTRUDA alone, which is partnered with Merck, is ongoing. And we have also made progress with the intratumoral immuno-oncology programs. Our OX40 ligand program has expanded into a Phase II dose expansion study in combination with durvalumab in patients with ovarian cancer and is actively recruiting patients. The Phase I program with our triplet of OX40 ligand IL-23 and IL-36 gamma is ongoing and data were recently presented at ASCO. You can find the link for the data at the bottom of the slide. Within our systemic intracellular therapeutics modality, both MMA and PA studies remain on pause due to COVID-19 disruptions. Finally, our partner-led programs, including the mutant KRAS vaccine with Merck and IL-12 and VEGF with AstraZeneca continues.

現在讓我快速回顧一下我們的其他臨床項目。在全身分泌和細胞表面治療方面，我很高興地報告，mRNA-1944 I 期試驗的另外 2 個隊列最近已完成入組。提醒一下，在此程序中，mRNA-1944 編碼針對基孔肯雅病毒的 IgG 抗體。另外 2 個隊列正在測試靜脈輸注 mRNA-1944，劑量為 0.6 mg/kg 高劑量，並進行類固醇術前用藥，以及 2 個劑量 0.3 mg/kg，不進行類固醇術前用藥，間隔一周。我們與默克合作的個性化癌症疫苗聯合 KEYTRUDA 與單獨 KEYTRUDA 的隨機 II 期試驗正在進行中。我們在瘤內免疫腫瘤學項目方面也取得了進展。我們的 OX40 配體項目已擴展到與 durvalumab 聯合治療卵巢癌患者的 II 期劑量擴展研究，並正在積極招募患者。我們的 OX40 配體 IL-23 和 IL-36 gamma 三聯體的 I 期項目正在進行中，數據最近在 ASCO 上公佈。您可以在幻燈片底部找到數據的鏈接。在我們的全身細胞內治療模式中，MMA 和 PA 研究由於 COVID-19 的干擾而仍處於暫停狀態。最後，我們的合作夥伴主導的項目，包括與默克公司合作的突變型 KRAS 疫苗以及與阿斯利康公司合作的 IL-12 和 VEGF 疫苗，仍在繼續。

Slide 18 is a snapshot of our development pipeline, with mRNA-1273 in Phase III and CMV in preparation for a Phase III start in 2021. We have 4 trials now in Phase II and 2 preparing for Phase II and 10 development candidates in Phase I, with a further 9 in preclinical studies.

幻燈片18 是我們的開發流程的快照，其中mRNA-1273 處於III 期，CMV 正在為2021 年啟動III 期做準備。我們現在有4 個試驗處於II 期，2 個試驗正在為II 期做準備， 10 個候選開發藥物處於I 期，還有 9 項正在進行臨床前研究。

So with such a broad development pipeline, we anticipate many readouts and next steps in the near term and they are listed on Slide 19. And these include, as I mentioned, the Phase I results from the older and elderly aged cohorts Phase II and interim analysis for Phase III for mRNA-1273, the Phase II results from CMV in the third quarter and the complete Phase I data from the additional cohorts from our antibody against the chikungunya virus.

因此，有瞭如此廣泛的開發渠道，我們預計短期內會有許多讀數和後續步驟，它們列在幻燈片19 上。正如我提到的，這些包括來自老年人和老年群體的第一階段結果第二階段和中期mRNA-1273 的 III 期分析、第三季度 CMV 的 II 期結果以及來自我們針對基孔肯雅病毒的抗體的其他隊列的完整 I 期數據。

With that, let me turn the call over to Stephen.

現在，讓我把電話轉給斯蒂芬。

Thank you, Tal. I'd like to start our discussion on mRNA-1273 value by -- on Slide 21, just recapping the scale of the loss that we've all been facing. It is remarkable that this pandemic has harmed millions of people already. And our hearts go out to those who've lost loved ones or have been made sick themselves. Given the scale of that devastation, it is hard to believe that just 7 months ago, none of us had ever heard of SARS-CoV-2 or COVID-19. Globally now, over 18 million people have had confirmed infections with the virus and almost 700,000 have died. In the U.S., that looks like 4.7 million confirmed cases and 150,000 deaths. And the estimates are that by year-end in the U.S. alone, there could be up to 400,000 deaths in this country.

謝謝你，塔爾。我想從幻燈片 21 開始我們對 mRNA-1273 價值的討論，只是回顧一下我們都面臨的損失規模。值得注意的是，這種流行病已經傷害了數百萬人。我們的心與那些失去親人或自己患病的人同在。鑑於這場破壞的規模，很難相信就在 7 個月前，我們還沒有聽說過 SARS-CoV-2 或 COVID-19。目前，全球已有超過 1800 萬人確診感染該病毒，近 70 萬人死亡。在美國，確診病例為 470 萬例，死亡人數為 15 萬人。據估計，到年底，僅美國就有多達 40 萬人死亡。

What we're learning about the virus almost every day is that it may have a number of long-term sequela beyond the short-term impacts of the disease. So beyond the pulmonary infection, pneumonia, acute respiratory distress syndrome and pulmonary embolism that we see, there have been increasing reports of other coagulation disorders, cardiac injury and long-term sequela as well as disturbing reports of potential long-term neurologic complications and potential inflammatory syndromes in children. Clearly, we're learning more and more every day about the terrible devastation of this virus. And it's absolutely imperative that we and others advance the vaccine to try and blunt this pandemic and control these long-term sequela.

我們幾乎每天都了解到這種病毒除了疾病的短期影響之外，還可能產生許多長期後遺症。因此，除了我們看到的肺部感染、肺炎、急性呼吸窘迫綜合徵和肺栓塞之外，關於其他凝血障礙、心臟損傷和長期後遺症的報告也越來越多，以及潛在的長期神經系統並發症和潛在的令人不安的報告。兒童炎症綜合徵。顯然，我們每天都越來越了解這種病毒的可怕破壞。我們和其他人絕對有必要改進疫苗，以試圖遏制這種流行病並控制這些長期後遺症。

So on Slide 22. In trying to assign a value to a vaccine during a pandemic such as this, there are a number of approaches, but one of the most established is using incremental cost-effective ratios. Using a health economic assessment framework, you usually look just at health care costs, really the direct medical costs associated with caring for the disease. Through the ICER analysis, we looked at the incremental change in costs divided by the incremental change in health outcome. And the health outcome, the value of that improvement is measured based on willingness to pay thresholds, generally $50,000 to $150,000 per quality adjusted life years.

在幻燈片 22 上。在像這樣的大流行期間，在嘗試為疫苗分配價值時，有多種方法，但最成熟的方法之一是使用增量成本效益比率。使用健康經濟評估框架，您通常只關注醫療保健成本，實際上是與治療疾病相關的直接醫療成本。通過 ICER 分析，我們將成本的增量變化除以健康結果的增量變化。至於健康結果，即改善的價值是根據支付意願閾值來衡量的，通常每個質量調整生命年支付 50,000 美元至 150,000 美元。

Now on Slide 22, I'm presenting a recently completed analysis by Quadrant Health Economics looking at an ICER at a $50,000 quality threshold. This analysis looked just at the short-term benefits of vaccination during a pandemic. And what I mean by that is just the value created in the first year after rolling out broadly of a vaccine. Now scenarios depend on which populations you're looking at and the value also depends upon the epidemiology of the virus that's ongoing. But looking at a current trajectory of infection, in terms of epidemiology and vaccinating all adults, meaning those 18-plus, the ICER $50,000 value of the vaccine would be approximately $300 per course. If you focused vaccination just initially in the high-risk populations, say those over the age of 65, that value expands substantially, not surprisingly given the high burden of disease in that population. Obviously, as transmission increases, the potential value of vaccine significantly increases beyond that.

現在，在幻燈片 22 上，我將介紹 Quadrant Health Economics 最近完成的一項分析，該分析著眼於 50,000 美元質量閾值的 ICER。該分析僅著眼於大流行期間接種疫苗的短期益處。我的意思是指廣泛推出疫苗後第一年創造的價值。現在的情況取決於您所關注的人群，其價值還取決於正在發生的病毒的流行病學。但從流行病學和對所有成年人（即 18 歲以上）接種疫苗的角度來看，目前的感染軌跡，該疫苗的 ICER 50,000 美元價值約為每個療程 300 美元。如果您最初將疫苗接種集中在高危人群（例如 65 歲以上的人群）中，則該值會大幅增加，考慮到該人群的高疾病負擔，這一點並不奇怪。顯然，隨著傳播的增加，疫苗的潛在價值顯著增加。

Now on Slide 23. It's important to note the limitations of these ICER-type analyses. So while there is obviously a lot of value in a vaccine in directly impacting the health care costs, such analysis does not look at the long-term sequela and long-term disability potential of a disease like COVID-19. It also does nothing to capture the social disruption that's having a huge impact on all of our lives, nor does it do anything to reflect the economic loss that is rampant across our economies globally.

現在看幻燈片 23。值得注意的是這些 ICER 類型分析的局限性。因此，雖然疫苗在直接影響醫療保健成本方面顯然具有很大價值，但此類分析並未考慮像 COVID-19 這樣的疾病的長期後遺症和長期殘疾潛力。它也無助於捕捉對我們所有人的生活產生巨大影響的社會混亂，也無助於反映全球經濟中普遍存在的經濟損失。

And with that, I'd like to turn it over to Stéphane to talk to our approach.

說到這裡，我想把它交給 Stéphane 來討論我們的方法。

Thank you, Stephen, for this value framing.

謝謝斯蒂芬的這個價值框架。

I think it is most appropriate for me to start with Moderna's mission. We set out nearly 10 years ago now with a mission to deliver on mRNA science to create a new generation of medicines for patients. Our mission has been a compass for almost a decade and we continue for the long term.

我認為從Moderna的使命開始對我來說是最合適的。我們在近 10 年前就開始了我們的使命，即利用 mRNA 科學為患者創造新一代藥物。近十年來，我們的使命一直是指南針，並且我們將長期堅持下去。

On Slide 25, I want to share our approach to delivering value during the COVID-19 pandemic. During this pandemic and throughout the development process of mRNA-1273, our promise to deliver for patients has never been clearer. We have a responsibility to do everything we can to develop a safe and effective vaccine. We have invested in manufacturing at risk ahead of approval to ensure supply if our COVID-19 vaccine candidate is approved. We are working with governments around the world and others to ensure the vaccine is accessible regardless of our ability to pay. And we will be responsible on price well below value during the pandemic.

在幻燈片 25 上，我想分享我們在 COVID-19 大流行期間提供價值的方法。在這次大流行期間以及整個 mRNA-1273 的開發過程中，我們為患者提供服務的承諾從未如此明確。我們有責任盡一切努力開發安全有效的疫苗。我們在批准之前對處於風險中的生產進行了投資，以確保我們的 COVID-19 候選疫苗獲得批准後的供應。我們正在與世界各國政府和其他機構合作，確保無論我們的支付能力如何，都能獲得疫苗。在大流行期間，我們將對遠低於價值的價格負責。

Let me now turn to Slide 26 and give you some more specifics. First, as we thought about responsible pricing, we concluded it is important to consider different time horizons. We are currently under pandemic as defined by the WHO. At Moderna, like many public health experts, we believe that SARS-CoV-2 virus is not going away and that there will be a need to vaccinate people or give them a boost for many years to come. So we think about 2 time horizons. The pandemic period as defined by WHO and the endemic period. During the pandemic period, we are priced well below value with pre-approval supply agreements mostly to governments. To date, smaller volume agreements have been executed between $32 and $37 per gross. Larger volume agreements under discussion will be at a lower price for higher volumes. In the endemic period, pricing considerations will follow traditional dynamics and market forces, including vaccine efficacy and the competitive landscape. We will look to price in line with other innovative commercial vaccines. We expect traditional approaches to vaccine purchase and distribution in the endemic phase.

現在讓我轉向幻燈片 26，為您提供更多細節。首先，當我們考慮負責任的定價時，我們得出的結論是考慮不同的時間範圍很重要。我們目前正處於世界衛生組織定義的大流行時期。在 Moderna，與許多公共衛生專家一樣，我們相信 SARS-CoV-2 病毒不會消失，並且在未來許多年裡都需要為人們接種疫苗或加強免疫。所以我們考慮兩個時間範圍。世界衛生組織定義的大流行期和流行期。在大流行期間，我們的定價遠低於價值，預先批准的供應協議主要是針對政府的。迄今為止，已執行的小批量協議在每毛額 32 至 37 美元之間。正在討論的較大批量協議將以較低的價格獲得較高的產量。在流行期間，定價考慮因素將遵循傳統動態和市場力量，包括疫苗功效和競爭格局。我們將尋求與其他創新商業疫苗一致的定價。我們預計在流行階段將採用傳統的疫苗購買和分發方法。

With this, let me now turn to David for him to walk through our financials. David?

現在，讓我請大衛來介紹一下我們的財務狀況。大衛？

Okay. Thank you, Stéphane.

好的。謝謝你，斯特凡。

Turning to Slide #28. In today's press release, we reported our second quarter unaudited 2020 financial results.

轉向幻燈片 #28。在今天的新聞稿中，我們報告了 2020 年第二季度未經審計的財務業績。

We ended Q2 2020 with cash and investments of $3.1 billion compared to $1.7 billion at the end of Q1. The increase is driven by the capital raise in May of this year. Net cash used in operating activities was $130 million for the first half of 2020 compared to $253 million in 2019. The decrease in 2020 is mainly due to deposits of $75 million received as of June 30 for potential future supply of mRNA-1273. Net cash used in operating activities for the first half of 2019 also included $22 million of in-licensing payments to Cellscript to sublicense certain patent rights. Cash used for purchases of property and equipment was $25 million for the first half of 2020 compared to $18 million in 2019. Total revenue was $66 million for Q2 2020 compared to $13 million for the same period in 2019. Total revenue was $75 million in the first half of 2020 compared to $29 million for the same period in 2019. Total revenue increased for both the 3- and 6-month periods in 2020 due to increases in collaboration and grant revenue. The collaboration revenue increases were mainly attributable to an increase in revenue in the second quarter, particularly from AstraZeneca. The increases in grant revenue were primarily due to our BARDA agreement related to the development of our vaccine candidate, mRNA-1273.

截至 2020 年第二季度末，我們的現金和投資為 31 億美元，而第一季度末為 17 億美元。這一增長是由今年 5 月份的融資推動的。 2020 年上半年經營活動使用的現金淨額為1.3 億美元，而2019 年為2.53 億美元。2020 年的減少主要是由於截至6 月30 日收到的7500 萬美元存款，用於未來潛在的mRNA -1273 供應。 2019 年上半年經營活動使用的現金淨額還包括向 Cellscript 支付的 2200 萬美元的許可費用，用於對某些專利權進行再許可。 2020 年上半年用於購買財產和設備的現金為2500 萬美元，而2019 年為1800 萬美元。2020 年第二季度的總收入為6600 萬美元，而2019 年同期為1300 萬美元。2020 年第二季度的總收入為7500 萬美元。 2020 年上半年的收入為2900 萬美元，而2019 年同期為2900 萬美元。由於合作和贈款收入的增加，2020 年3 個月和6 個月期間的總收入均有所增加。合作收入的增長主要歸因於第二季度收入的增長，尤其是來自阿斯利康的收入增長。撥款收入的增加主要是由於我們與候選疫苗 mRNA-1273 的開發相關的 BARDA 協議。

Research and development expenses were $152 million for the second quarter of 2020 compared to $128 million for the same period in 2019. Research and development expenses were $267 million in the first half of 2020 compared to $258 million for the same period in 2019. The increases for both 3- and 6-month periods in 2020 were mainly due to increased headcount and mRNA-1273 clinical development activities. Overall, in both periods, we saw a significant increase in expenses for prophylactic vaccines modality as a result of our focus on mRNA-1273, while expenses related to the rest of the portfolio were stable.

2020 年第二季度的研發費用為 1.52 億美元，而 2019 年同期為 1.28 億美元。2020 年上半年的研發費用為 2.67 億美元，而 2019 年同期為 2.58 億美元。 2020 年3 個月和6個月期間的增長主要是由於人數增加和mRNA-1273 臨床開發活動。總體而言，在這兩個時期，由於我們專注於 mRNA-1273，我們發現預防性疫苗方式的費用顯著增加，而與其他產品組合相關的費用則保持穩定。

General and administrative expenses were $36 million for Q2 2020 compared to $29 million for the same period in 2019. Expenses were $61 million for the first half of 2020 compared to $56 million for the same period in 2019. The increases for both periods were mainly driven by increases in personnel and legal expenses.

2020 年第二季度的一般及行政費用為3600 萬美元，而2019 年同期為2900 萬美元。2020 年上半年的費用為6100 萬美元，而2019 年同期為5600 萬美元。這兩個時期的增長主要是由於人員和法律費用的增加。

Turning to cash flow from net operating activity and purchase of property and equipment on Slide 29.

轉向幻燈片 29 上的淨經營活動以及購買財產和設備的現金流。

Cash used in operating activity and for purchase of property and equipment was $118 million, excluding the $75 million for deposits received as of June 30 for potential supply of mRNA-1273, in line with previous trends. On a reported basis, including the mentioned $75 million deposits, cash used in operating activities and purchase of PP&E were $43 million for the quarter.

用於經營活動以及購買財產和設備的現金為 1.18 億美元，不包括截至 6 月 30 日收到的 mRNA-1273 潛在供應的 7500 萬美元存款，與之前的趨勢一致。根據報告，包括上述 7500 萬美元存款在內，本季度用於經營活動和購買固定資產和設備的現金為 4300 萬美元。

Turning now to updated guidance for 2020. Our guidance today maintains the metric of net cash used in operating activities and for purchase of property and equipment. We will adopt additional guidance metrics in the future as the business progresses towards commercialization. As always, we'll be interested in any advice you may have on how we can be clear, concise and comprehensible.

現在轉向 2020 年更新的指導。我們今天的指導維持了經營活動以及購買財產和設備所使用的淨現金指標。隨著業務邁向商業化，我們未來將採用額外的指導指標。與往常一樣，我們對您提出的任何有關如何使我們的內容變得清晰、簡潔和易於理解的建議感興趣。

On an overall basis, the net cash used in operating activities and purchases of property and equipment in 2020 will increase to $0.65 billion to $0.85 billion from the prior guidance of approximately $0.5 billion for the year. Updated guidance for 2020 reflects ongoing investments in Moderna's broad mRNA clinical and preclinical pipeline as well as the significant activities associated with our efforts to advance our mRNA-1273 COVID vaccine toward approval and launch. With regard to the ongoing investment in our base business, we remain on track to prior plans where we continue to expect net cash used in operating activities and purchases of property and equipment to be approximately $0.5 billion in 2020.

總體而言，2020年用於經營活動以及購買財產和設備的淨現金將從此前指導的約5億美元增至6.5億美元至8.5億美元。 2020 年的更新指南反映了對 Moderna 廣泛的 mRNA 臨床和臨床前管道的持續投資，以及與我們為推動 mRNA-1273 COVID 疫苗獲得批准和上市而做出的努力相關的重大活動。關於對基礎業務的持續投資，我們仍按之前的計劃進行，我們繼續預計 2020 年用於經營活動以及購買財產和設備的淨現金約為 5 億美元。

Turning now to the financial impacts of our rapidly advancing mRNA-1273 COVID vaccine.

現在談談我們快速發展的 mRNA-1273 COVID 疫苗的財務影響。

First, expenses that fall under the scope of our BARDA agreement. These are primarily research and development activities to drive the COVID vaccine to licensure and scale up activities on the technical development and manufacturing side. As we expect a relatively close matching of expenses and reimbursement, we do not expect these activities to materially impact our cash flow, and hence, these are not shown separately on Slide 29.

首先，屬於我們 BARDA 協議範圍內的費用。這些主要是推動新冠疫苗獲得許可並擴大技術開發和製造方面活動的研發活動。由於我們預計費用和報銷的匹配相對接近，因此我們預計這些活動不會對我們的現金流產生重大影響，因此，這些活動不會在幻燈片 29 中單獨顯示。

Next, looking at the COVID vaccine related nonreimbursable investments, primarily for manufacturing of product to be commercialized in the U.S. and internationally. We expect the cash impact of COVID-related investments to be between $0.55 billion to $0.75 billion in 2020. This includes approximately $0.2 billion in capital investments, with the balance of the expenses related to raw materials and production activity in our network. Additionally, this investment includes initial commercial infrastructure build-out. The sum total of net cash used in operating activities for all of Moderna's business is expected to total $1.05 billion to $1.25 billion before consideration of customer deposits.

接下來，看看與新冠疫苗相關的無償投資，主要用於製造將在美國和國際上商業化的產品。我們預計 2020 年新冠相關投資的現金影響將在 5.5 億美元至 7.5 億美元之間。這包括約 2 億美元的資本投資，以及與我們網絡中的原材料和生產活動相關的費用餘額。此外，這項投資還包括最初的商業基礎設施建設。在考慮客戶存款之前，Moderna 所有業務的經營活動所使用的淨現金總額預計將達到 10.5 億至 12.5 億美元。

Also included in today's guidance are the deposits we have received to date for potential future supply of our COVID vaccine. Deposits as of July 31 totaled $0.4 billion, including $75 million received during the second quarter. We remain in active discussions with a number of potential customers and will update the status as the market evolves.

今天的指導意見還包括我們迄今為止收到的用於未來可能供應新冠疫苗的押金。截至 7 月 31 日，存款總額為 4 億美元，其中第二季度收到的存款為 7500 萬美元。我們仍在與許多潛在客戶進行積極討論，並將隨著市場的發展更新狀態。

In summary, on a net total company basis, we update our 2020 guidance for net cash used in operating activities to $0.65 billion to $0.85 billion for 2020. We expect this number to reduce as we receive further deposits.

總之，在公司淨總額的基礎上，我們將 2020 年經營活動使用的淨現金指引更新為 6.5 億至 8.5 億美元。我們預計隨著我們收到更多存款，這一數字將會減少。

As we progress towards approval and commercialization of mRNA-1273, there is heightened interest in several areas of accounting that will increasingly impact our reported results as we move forward. Slide 31 highlights several of these items.

隨著我們在 mRNA-1273 的批准和商業化方面取得進展，人們對幾個會計領域的興趣日益濃厚，隨著我們的前進，這些領域將越來越多地影響我們報告的結果。幻燈片 31 重點介紹了其中幾個項目。

Costs associated with prelaunch inventory are expensed to R&D in the period incurred. We will capitalize our inventory when regulatory approval and subsequent commercialization is determined to be probable, and we expect future economic benefits from sales to be realizable. Customer deposits for potential supply of mRNA-1273 are recorded as deferred revenue and will be recognized as revenue when revenue recognition criteria are met at a future date. Accounting for the BARDA grant follows a reimbursement model where we will recognize revenue as we perform services and closely match expenses as they are incurred. For purchase and supply agreements, we disclosed the aggregated amount of the purchase obligation that is fixed and determinable as per GAAP accounting requirements. This is regardless of whether these obligations have been recorded as actual costs in our financial statements in the current period.

與上市前庫存相關的成本在發生期間計入研發費用。當確定有可能獲得監管部門批准和隨後的商業化時，我們將把我們的庫存資本化，並且我們預計未來可以從銷售中獲得經濟利益。潛在供應 mRNA-1273 的客戶存款記錄為遞延收入，並將在未來日期滿足收入確認標準時確認為收入。 BARDA 補助金的會計處理遵循報銷模式，我們將在提供服務時確認收入，並在發生費用時密切匹配費用。對於採購和供應協議，我們披露了根據 GAAP 會計要求固定且可確定的採購義務總額。這與這些義務是否已在我們當期的財務報表中記錄為實際成本無關。

With that, I turn the call back to Stéphane for closing remarks.

說完，我將電話轉回給 Stéphane，讓其致閉幕詞。

Thank you, David.

謝謝你，大衛。

In closing, let me share with you a snapshot of Moderna today.

最後，讓我今天與大家分享一下 Moderna 的快照。

The company continues to progress its clinical pipeline and got closer in Q2 to becoming the commercial company. We have our first Phase III program with our COVID-19 vaccine, but we're also preparing the Phase III for our CMV vaccine. We have 3 programs in Phase II: CMV; personal cancer vaccine, PCV; and VEGF. And we're also preparing Phase II for our Zika vaccine and OX40 ligand development candidate in immuno-oncology. We have 8 programs in Phase I. We have had 12 positive Phase I readouts across 5 different technology modalities. The product development includes 7 vaccines for unmet medical needs, which, if approved, could be first-in-class vaccines. This includes our vaccines against COVID-19, CMV, hMPV plus PIV3 combo, RSV in older adults and RSV pediatric population, Zika and EBV. We have 5 immuno-oncology programs in clinical studies. We have 4 VEGF programs in both MMA and PA with open INDs. We have 2 autoimmune disease candidates with IL-2 and PD-L1 in preclinical studies.

該公司繼續推進其臨床管線，並在第二季度更接近成為商業公司。我們有第一個針對 COVID-19 疫苗的 III 期項目，但我們也在為 CMV 疫苗準備 III 期項目。我們二期有3個項目：CMV；個人癌症疫苗，PCV；和血管內皮生長因子。我們還正在為寨卡疫苗和免疫腫瘤學候選 OX40 配體開發候選藥物做第二階段準備。我們在第一階段有 8 個項目。我們已經在 5 種不同的技術模式中獲得了 12 個積極的第一階段讀數。該產品開發包括7種疫苗，用於滿足未滿足的醫療需求，如果獲得批准，這些疫苗可能是一流的疫苗。這包括我們針對 COVID-19、CMV、hMPV 加 PIV3 組合、老年人 RSV 和兒童 RSV、寨卡病毒和 EBV 的疫苗。我們有 5 個免疫腫瘤學項目正在進行臨床研究。我們在 MMA 和 PA 領域都有 4 個 VEGF 項目，並已開放 IND。我們有 2 種針對 IL-2 和 PD-L1 的自身免疫性疾病候選藥物處於臨床前研究中。

The foundations of Moderna has never been stronger, with over 2,000 healthy volunteers and participants enrolled in our studies as of the end of July, and that number will grow considerably over the coming weeks as we continue to enroll our 30,000 participants Phase III CoV study or COVID-19 vaccine candidate. We have over 1,000 employees. We have a fully integrated GMP site in Massachusetts and a strong experienced manufacturing partner in Lonza. Our biopharmaceutical partners are leaders in their specific fields, and include Merck, AZ and Vertex. And finally, with a strong balance sheet at the end of June, we have the ability to invest $3.1 billion to create value.

Moderna 的基礎從未如此堅固，截至7 月底，已有2,000 多名健康志願者和參與者參加了我們的研究，隨著我們繼續招募30,000 名參與者進行III 期冠狀病毒研究，這一數字將在未來幾週內大幅增長。 COVID-19 候選疫苗。我們有超過 1,000 名員工。我們在馬薩諸塞州擁有完全集成的 GMP 工廠，並在龍沙擁有經驗豐富的製造合作夥伴。我們的生物製藥合作夥伴是各自特定領域的領導者，包括默克 (Merck)、AZ 和福泰 (Vertex)。最後，憑藉 6 月底強勁的資產負債表，我們有能力投資 31 億美元來創造價值。

We have entered a new growth phase for our company. mRNA-1273 is now in Phase III. We have received approximately $400 million of cash for customer deposits for potential supply of mRNA-1273 as July 31. And we continue to discuss with many governments around the world who are interested in getting access to mRNA-1273.

我們公司已經進入了一個新的增長階段。 mRNA-1273 目前處於 III 期。截至 7 月 31 日，我們已收到約 4 億美元的客戶存款現金，用於 mRNA-1273 的潛在供應。我們將繼續與世界各地有興趣獲得 mRNA-1273 的許多政府進行討論。

The last 6 months have been extraordinary by many measures for our company. The next 6 months could see us of our first product filed for BLA approval.

從許多方面來看，過去 6 個月對我們公司來說都是不平凡的。接下來的 6 個月內，我們的第一個產品可能會申請 BLA 批准。

We know that we have a special opportunity, and we are committed to delivering on the promise of our science to bring forward a new class of medicines for patients. That is why we started this company. That is why we work hard every day. mRNA-1273 is the head of the spear. We have a large pipeline with more than 20 development candidates.

我們知道我們有一個特殊的機會，我們致力於兌現我們科學的承諾，為患者提供新型藥物。這就是我們創辦這家公司的原因。這就是我們每天努力工作的原因。 mRNA-1273是矛頭。我們擁有龐大的開發渠道，擁有超過 20 名開發候選者。

Since our founding, we have believed that it makes no sense that Moderna will be a 1-medicine company. It will be 0 if we fail to make mRNA science work or it will be many medicines if the first one gets to market, thanks to an FDA approval. That is because mRNA is an information molecule, which makes Moderna a unique biotech platform company.

自成立以來，我們一直認為 Moderna 成為一家單一藥品公司是沒有意義的。如果我們不能讓 mRNA 科學發揮作用，那麼它的價值將是 0，或者，如果第一個藥物進入市場，那麼由於 FDA 的批准，它將有很多藥物。這是因為 mRNA 是一種信息分子，這使得 Moderna 成為一家獨特的生物技術平台公司。

I would like to end our remarks by thanking the many people who participate in our clinical studies, including patients, healthy volunteers, physicians and nurses. I would like to thank our partners at the NIH and BARDA and in our biopharmaceutical partners.

在結束髮言時，我想感謝參與我們臨床研究的許多人，包括患者、健康志願者、醫生和護士。我要感謝 NIH 和 BARDA 的合作夥伴以及我們的生物製藥合作夥伴。

I would like to say a special thank you to Moderna team. They have done a remarkable job in Q2 during a very complex time, scaling Moderna quickly, while managing lockdown and many personal disruptions. I'm very proud of the team achievement in the first 7 months of 2020.

我要特別感謝 Moderna 團隊。他們在第二季度的非常複雜的時期做得非常出色，快速擴展了 Moderna，同時管理了封鎖和許多個人干擾。我對團隊在 2020 年前 7 個月取得的成就感到非常自豪。

With that, we are now happy to take any question. Operator?

至此，我們現在很樂意回答任何問題。操作員？

(Operator Instructions) I show our first question comes from the line of Matthew Harrison from Morgan Stanley.

（操作員說明）我表明我們的第一個問題來自摩根士丹利的馬修哈里森。

I guess two for me this morning. First, on manufacturing for 1273, can you give us an update on how much inventory you've built so far and where you are in terms of scaling to that 500 million dose per year run rate that you've previously highlighted?

我想今天早上我有兩個。首先，關於 1273 的製造，您能否向我們介紹一下您迄今為止已建立的庫存量以及您之前強調的每年 5 億劑運行率的進展情況？

And then second, I was hoping you could comment on some media reports we've seen over the last day or 2 about FDA potentially convening a panel for vaccines in October and I guess also comments that there is going to be real-time review of vaccines. And what exactly that means given the time lines potentially for your Phase III study?

And then second, I was hoping you could comment on some media reports we've seen over the last day or 2 about FDA potentially convening a panel for vaccines in October and I guess also comments that there is going to be real-time review of疫苗.考慮到您的 III 期研究可能的時間表，這到底意味著什麼？

Matthew, this is Tal. Let me maybe take the second question first and then I'll defer to Stéphane to take the first one. Look, I can't comment on media reports. I think that the -- we have been working very closely with the agency, as I'm sure my colleagues have from other companies, to make sure that we're locked up and give them the greatest, best visibility we can to our data as it emerges. We continue that dialogue as our Phase III is now enrolling. The Phase III trial has pretty clear, if you will, interim analysis and the statistical -- robust statistic plan that we had described in the past. But obviously, with the level of unmet need and more and more data emerging to substantiate the potential for benefit as we continue to accumulate safety data on the Phase III, I'm very happy to see that FDA continues to take a very proactive stance in evaluating the totality of the clinical data as it emerges. And as soon as I have any more insights than that, I would be more than happy to share it.

馬修，這是塔爾。讓我先回答第二個問題，然後我會聽從 Stéphane 回答第一個問題。聽著，我無法對媒體報導發表評論。我認為，我們一直在與該機構密切合作，就像我確信其他公司的同事一樣，以確保我們被鎖定並為他們提供我們數據的最大、最好的可見性正如它所出現的那樣。隨著第三階段的招募，我們將繼續進行這種對話。如果你願意的話，第三階段試驗有非常明確的中期分析和統計——我們過去描述過的穩健的統計計劃。但顯然，隨著我們繼續積累 III 期安全數據，隨著未滿足的需求水平和越來越多的數據出現來證實潛在的益處，我很高興看到 FDA 繼續採取非常積極主動的立場評估出現的全部臨床數據。一旦我有更多的見解，我會非常樂意分享。

Thank you, Tal. And Matthew, on the first question around manufacturing, we will not share inventory numbers at this time. What I can tell you is that, as we speak, our teams are making commercial products assuming the potential approval of mRNA-1273. So we are literally making products and stockpiling at risk. In term of the capacity, I'll confirm what we have said before, which is, for 2021, the 500 million dose per year continues to be our base plan, meaning the team has a good sense of how to execute over that plan. And the team continues to work really hard over many different approaches from new process equipment to debottleneck to find a path to 1 billion dose, which we still consider at this date as an upside. So the base of 500 million is our base case, and the team is still working hard to figure out how we can get closer to a 1 billion capacity for 2021 output.

謝謝你，塔爾。馬修，關於製造業的第一個問題，我們目前不會分享庫存數據。我可以告訴你的是，就在我們說話的時候，我們的團隊正在生產商業產品，假設 mRNA-1273 可能獲得批准。因此，我們實際上是在冒著風險生產產品和儲存庫存。在產能方面，我會確認我們之前所說的，即到2021年，每年5億劑仍然是我們的基本計劃，這意味著團隊對如何執行該計劃有很好的認識。該團隊繼續在許多不同的方法上努力工作，從新的工藝設備到消除瓶頸，以找到達到 10 億劑量的途徑，我們迄今為止仍然認為這是一個好處。因此，5 億的產能是我們的基本情況，團隊仍在努力研究如何才能使 2021 年的產量接近 10 億產能。

Our next question comes from the line of Ted Tenthoff from Piper Sandler.

我們的下一個問題來自 Piper Sandler 的 Ted Tenthoff。

Great. Question with regard to assumed infection rate for the Phase III. Obviously, this is going to be somewhat dependent on sort of where you're enrolling and things like that. So what can you tell us about the general assumed infection rate and kind of how many infections you may need to see to be able to power the Phase III study of that size?

偉大的。關於第三階段假設感染率的問題。顯然，這在某種程度上取決於您在哪裡註冊以及類似的事情。那麼，您能告訴我們關於一般假設的感染率以及您可能需要觀察多少感染才能為這種規模的 III 期研究提供動力嗎？

Ted, it's Tal. It's a great question. The challenge is that I don't know how to build those assumptions given the huge, wide variability we've seen in actual infections rate. So the number of infections you need to see correlates to the number of cases required to pass the interim. And as we've disclosed, it's roughly a little over 50, a little over 100 and 150-some for the first and second interim and then the final. That's the number of cases. And I think the advantage of running a 30,000 subject trial with 15,000 of them getting active vaccine and the rest as the placebo is that the larger that cohort, the more likely are to see those cases early. But it's of course a direct function of infection rates.

特德，我是塔爾。這是一個很好的問題。挑戰在於，鑑於我們在實際感染率中看到的巨大且廣泛的變化，我不知道如何建立這些假設。因此，您需要看到的感染數量與通過過渡期所需的病例數量相關。正如我們所披露的，第一次和第二次中期以及決賽的人數大約為 50 多一點、100 多一點、150 多一點。這就是病例數。我認為進行 30,000 名受試者試驗（其中 15,000 人接種活性疫苗，其餘人作為安慰劑）的優勢在於，隊列規模越大，越有可能儘早發現這些病例。但這當然是感染率的直接函數。

I think the -- sort of if you step back philosophically, we designed with our partners at NIH such a large trial, with the initial goal, not knowing at the time what the infection rates were. You kind of just take a cross-country average. You figure you're going to be able to enrich it somewhat, and you make it broad enough so that it's representative of the diverse population. I think what we've seen is an anticipated acceleration of the time line to cases, not just by us, but I think, by many people out there, recognizing that infection rates currently in the U.S. are actually higher, certainly in the areas in which we're doing this trial than maybe we would have thought 3, 4 months ago. So I think the initial projections and people smarter than me have sort of made them was that we had expected to see the cases come in towards the end of the year or by the end of the year. I think with higher infection rates currently, there may be an acceleration of that, but it's extremely hard to predict. We like everybody else sort of follow these on a daily and weekly moving average. And I don't think I've got a better crystal ball than anybody else in that domain. Over.

我認為，如果你退一步思考，我們與美國國立衛生研究院的合作夥伴一起設計瞭如此大規模的試驗，最初的目標是不知道當時的感染率是多少。你只需取跨國平均值即可。你認為你將能夠在某種程度上豐富它，並且使它足夠廣泛，以便它能夠代表不同的人群。我認為我們所看到的是病例時間線的預期加速，不僅僅是我們，而且我認為，很多人都認識到美國目前的感染率實際上更高，尤其是在以下地區我們正在做的這個試驗可能比我們三四個月前想像的要好。因此，我認為最初的預測和比我聰明的人做出的預測是，我們預計會在今年年底或年底看到病例。我認為，由於目前感染率較高，這種情況可能會加速，但很難預測。我們喜歡其他人遵循每日和每週移動平均線。我不認為我比這個領域的其他人擁有更好的水晶球。超過。

Our next question comes from Salveen Richter from Goldman Sachs.

我們的下一個問題來自高盛的 Salveen Richter。

So with regard to the volume agreements that will be executed at a higher price point for smaller versus larger volume orders, how are you delineating between the smaller versus larger in terms of volumes? And then secondly, if 2 different companies developing vaccines for SARS-CoV-2 both use, let's just say, the print 50 assays, are those assays identical? So could you actually look at these programs head to head?

因此，對於較小訂單與較大訂單量的訂單將以較高價格執行的成交量協議，您如何在交易量方面區分較小訂單與較大訂單？其次，如果兩家不同的公司開發 SARS-CoV-2 疫苗，都使用打印的 50 種檢測方法，那麼這些檢測方法是否相同？那麼你真的能直接看看這些程序嗎？

So let me take the first two and I will turn it over to Tal or Stephen for the second one. On the volume agreements, we are not disclosing a very precise cutoff because, as you can appreciate, there's a lot of different components that go into getting those agreement to a finish line with potential customers. I think small is more kind of in the millions, and large, as you can imagine, probably bigger countries will be a very different ballpark.

因此，讓我先完成前兩個任務，然後將第二個任務交給塔爾或斯蒂芬。關於批量協議，我們沒有透露非常精確的截止日期，因為正如您所理解的，有很多不同的組成部分需要與潛在客戶達成這些協議。我認為小國家更適合數以百萬計的國家，而大國家，正如你可以想像的那樣，可能更大的國家將是一個非常不同的情況。

Stephen, you want to -- or Tal, talk about the print 50 assays, please?

Stephen，您想——或者 Tal，談談打印 50 次檢測嗎？

Yes. This is Tal. I'll take that -- a run at that. It's a great question. I think all of us are trying to look at them and understand the assays. There are big differences because those assays are not standardized, and you've seen a range of print 50s, you've seen assays against live virus, pseudo virus neutralization. What's clear is that all of these correlate with each other pretty well, but there also are differences. And I think if you look across, that's why everybody is trying to sort of report it out as a ratio to the convalescent plasma. The challenge there is, again, there is no standard panel for what the convalescent plasma is, so everybody is using different panels of serum.

是的。這是塔爾。我會採取這一點——嘗試一下。這是一個很好的問題。我想我們所有人都在努力研究它們並理解這些檢測方法。存在很大差異，因為這些檢測方法沒有標準化，您已經看到了一系列打印的 50 秒，您已經看到了針對活病毒、偽病毒中和的檢測方法。顯而易見的是，所有這些都相互關聯得很好，但也存在差異。我想，如果你仔細看看，這就是為什麼每個人都試圖將其報告為與恢復期血漿的比率。再次面臨的挑戰是，對於恢復期血漿沒有標準的組合，因此每個人都使用不同的血清組合。

I think the ballpark estimates are probably roughly comparative. My sense is sort of between half a log and a log of each other for sure, maybe even tighter than that. But it's hard to drill down and get confidence that you're really comparing apples-to-apples. And there's certainly, I don't think, identical -- people try to set them up in identical ways, but you're going to have minor variances.

我認為大概的估計可能是粗略的比較。我的感覺肯定介於半根木頭和一根木頭之間，甚至可能比這更緊密。但很難深入研究並確信你確實在進行同類比較。當然，我不認為它們是相同的——人們試圖以相同的方式設置它們，但會有細微的差異。

There's also variability in the preclinical models reported. You can see different -- especially in the NHP, you can see people using different inoculums or inocular levels of different severity of infections in the different models and then reporting out protection or not.

報告的臨床前模型也存在差異。你可以看到不同的情況——尤其是在 NHP 中，你可以看到人們在不同的模型中使用不同的接種物或不同感染嚴重程度的眼內水平，然後報告是否有保護作用。

So unfortunately, we're still relatively in the early days. I think the good news is that you've seen for our data pretty robust titers in every which assay you measure as it relates to convalescent plasma. I'm happy for all of us that I think we're probably not alone. There are going to be other vaccines that also seem to be getting close to that. And so ultimately, we'll all get wiser when we see the Phase III results. Over.

不幸的是，我們仍處於相對早期階段。我認為好消息是，您已經從我們的數據中看到，在您測量的與恢復期血漿相關的每項檢測中，滴度都相當強勁。我為我們所有人感到高興，我認為我們可能並不孤單。還會有其他疫苗似乎也接近這一點。因此，最終，當我們看到第三階段的結果時，我們都會變得更加明智。超過。

Our next question comes from Michael Yee from Jefferies.

我們的下一個問題來自 Jefferies 的 Michael Yee。

Appreciate all the updates. Two quick ones for me. First, you're seeing -- or the market has seen a lot of contracts being deployed both in U.K. This morning, also another U.S. contract deployed to J&J. Could you just put into some context for us how we should think about Moderna's position here and a presumption of a diversified stockpile, maybe why or why not there hasn't been anything to announce just yet? Maybe just make some broad comments about that.

感謝所有更新。對我來說兩個快點。首先，你會看到——或者市場今天早上看到很多合同部署在英國，還有另一份美國合同部署在強生公司。您能否為我們介紹一下我們應該如何考慮 Moderna 在這裡的立場以及多元化庫存的假設，也許為什麼或為什麼還沒有任何消息可以宣布？也許只是對此發表一些廣泛的評論。

And then the second question, I guess, is since you've reported data, there has been obviously a lot of other platforms with data that have come out, both adeno and protein last night. Maybe just make a comment about how to put that into perspective and the market's enthusiasm or people's enthusiasm about those data sets.

然後第二個問題，我想，自從你報告了數據以來，顯然有很多其他平台已經公佈了昨晚的數據，包括腺苷和蛋白質。也許只是評論一下如何正確看待這一點以及市場的熱情或人們對這些數據集的熱情。

Good. Thank you, Michael. Let me talk a bit about contracts and then I will hand over to Tal. So as you know, Michael, to get to a contract, you need 2 parties to agree on terms. As I said in my remarks, we are discussing with governments around the world. As you know, we have a long-standing relationship with the U.S. government with different agencies in BARDA, DARPA and NIH. The contracts that have been signed so far are contractors so -- that actually literally around the world in all the key regions. And so as we get to the right place, of course, we will make the right announcement as appropriate.

好的。謝謝你，邁克爾。讓我談談合同，然後我將交給塔爾。正如你所知，邁克爾，要簽訂合同，你需要兩方就條款達成一致。正如我在發言中所說，我們正在與世界各國政府進行討論。如您所知，我們與美國政府、BARDA、DARPA 和 NIH 等不同機構保持著長期合作關係。到目前為止，已經簽署的合同都是承包商——實際上是在世界各地的所有關鍵地區。因此，當我們到達正確的地方時，我們當然會在適當的時候發布正確的公告。

Our understanding, as has been said publicly, is that different governments have different strategy. Some of them wants to build a portfolio to manage risk because of course, at this stage, nobody knows which vaccine will get approved. Nobody knows the different efficacy, which will be most probably very important especially for the population at risk, the elderly people with comorbidity factor. To them, the difference in efficacy might be very, very important. And so I think what we're seeing is the government is doing what I think we would do or you would do if you were running the country or trying to get -- take over health of a large group of people, which is to build the portfolio, thinking about both risk of success, performance of a product and also covering the country.

正如公開所說，我們的理解是不同的政府有不同的策略。他們中的一些人希望建立一個投資組合來管理風險，因為當然，在現階段，沒有人知道哪種疫苗會獲得批准。沒有人知道不同的功效，這很可能非常重要，特別是對於高危人群、有合併症因素的老年人來說。對他們來說，功效上的差異可能非常非常重要。因此，我認為我們看到的是，政府正在做我認為我們會做的事情，或者如果你正在治理國家或試圖接管一大群人的健康，你會做的事情，那就是建立投資組合，既考慮成功的風險、產品的性能，又考慮覆蓋全國。

So as you see, a lot of those agreements have options built into them, which I think, again, makes a lot of sense. As we said, we want to be part of the solution and make sure that we can be helpful. As we've said, we are cautiously optimistic about the good clinical data so far of our vaccine. And we want to make sure we can help as many people as we can around the world, as many governments as we can, to help protect as many people as we can to kind of stop this pandemic.

正如您所看到的，許多協議都內置了選項，我認為這很有意義。正如我們所說，我們希望成為解決方案的一部分，並確保我們能夠提供幫助。正如我們所說，我們對疫苗迄今為止良好的臨床數據持謹慎樂觀態度。我們希望確保我們能夠幫助世界各地盡可能多的人、盡可能多的政府，幫助保護盡可能多的人，以阻止這一流行病。

Tal, can I turn this over to you for the second part of the question for Michael?

塔爾，我可以把這個交給你作為邁克爾問題的第二部分嗎？

Yes. It's a great question on how the platforms are starting to stack up with -- to each other. I think we -- I think our data continue to be as good or better than anything anybody's reported, both in terms of what we're able to show in neutralizing antibodies and in terms of the challenge we do in the nonhuman primate and the ability to completely eradicate or eliminate the [power] application of both the lung and the nose.

是的。這是一個很好的問題，即這些平台如何開始相互疊加。我認為我們的數據仍然與任何人報告的一樣好或更好，無論是在我們能夠在中和抗體中顯示的內容方面，還是在我們在非人類靈長類動物中所做的挑戰和能力方面。徹底根除或消除肺和鼻的[力]運用。

It's been nice to us to see Pfizer validating our data in a way with the BioNTech contract. Of course, we're still very curious to see what they're taking into Phase II and III because, reportedly, they're picking a different construct than the one for which they've shown data. I think the adeno vectors writ large, it's been an interesting story initially. It's pretty clear that there's less expectation for their ability to boost given the nature of their platform. And indeed, the first one, I don't think boosted at all.

我們很高興看到輝瑞通過 BioNTech 合同的方式驗證我們的數據。當然，我們仍然很好奇他們在第二階段和第三階段採取了什麼措施，因為據報導，他們選擇了一種與他們所展示的數據不同的結構。我認為腺病毒載體很重要，最初這是一個有趣的故事。很明顯，鑑於其平台的性質，人們對他們的提升能力的期望較低。事實上，我認為第一個根本沒有得到提升。

The AstraZeneca-Oxford data, I think, are encouraging in that they can get with a boost apparently to levels of convalescent plasma. Hard to say, very early data. But I think even though they dosed more than 1,000 subjects, they've showed data for 10 which they gave a prime boost. So I'm encouraged by those data, and I hope that, that's enough. I suspect that if that ends up being the case, then hopefully, for all of us, you will see them sort of be able to reach the minimal bar. But I'm encouraged by our data and expect that they will translate into -- I'm optimistic that they'll translate into higher point estimates for efficacy.

我認為阿斯利康-牛津大學的數據令人鼓舞，因為它們可以明顯提高恢復期血漿水平。很難說，非常早期的數據。但我認為，儘管他們對 1,000 多名受試者進行了給藥，但他們還是展示了 10 名受試者的數據，並對這些受試者給予了極大的促進作用。所以我對這些數據感到鼓舞，我希望這已經足夠了。我懷疑，如果情況確實如此，那麼希望我們所有人都能看到他們能夠達到最低標準。但我對我們的數據感到鼓舞，並預計它們將轉化為——我樂觀地認為它們將轉化為更高的功效估計值。

We saw Novavax data last night. I think any of us who's been following the field of vaccines anticipated that a recombinant protein done the right way with a strong adjuvant could be effective. I think they're -- certainly, their neutralizing antibody data are encouraging. And ultimately, I think the Phase III results are going to be required now to really understand fully the point estimate for efficacy as well as a better understanding of the reactogenicity and safety profile of these various approaches.

我們昨晚看到了 Novavax 的數據。我認為我們任何一個一直關注疫苗領域的人都預計，以正確的方式與強佐劑一起使用的重組蛋白可能會有效。我認為他們——當然，他們的中和抗體數據令人鼓舞。最終，我認為現在需要 III 期結果才能真正完全理解療效的點估計，以及更好地理解這些不同方法的反應原性和安全性。

So in summary, I think the mRNA platforms are clearly there with our data looking great. I think Novavax did a very nice progress. And I think the adeno vectors, I hope they get there, but I think they're going to struggle to boost. And I think all -- anybody who's done a boost or is able to show a boost is able to show as immunology would anticipate a very nice potentiation with the booster shot. Over.

總而言之，我認為 mRNA 平台顯然已經存在，我們的數據看起來很棒。我認為 Novavax 取得了非常好的進展。我認為腺病毒載體，我希望它們能到達那裡，但我認為它們將很難增強。我認為，任何已經進行過加強或能夠顯示出加強效果的人都能夠表現出免疫學預期的加強注射會產生非常好的增強作用。超過。

Our next question comes from the line of Gena Wang from Barclays.

我們的下一個問題來自巴克萊銀行的 Gena Wang。

I have two questions. So the first one is regarding the Phase III primary endpoint. Just wondering how do you count infection? I think according to the clinicaltrials.gov, it's basically a number of participants with the first occurrence of COVID-19 starting 14 days after second dose. Just wondering, is there a time cutoff so that every patient will have the same time exposure? Or will you report it as event per 1,000 patient here?

我有兩個問題。第一個是關於 III 期主要終點。只是想知道如何計算感染率？我認為根據 ClinicalTrials.gov 的數據，基本上有許多參與者在第二次接種後 14 天開始首次出現 COVID-19。只是想知道，是否有一個時間限制，以便每個患者都有相同的暴露時間？或者您會將其報告為這裡每 1,000 名患者的事件嗎？

And the second question is regarding the Phase I/Phase II data update, hopefully, this month or next month. So will we see more meaningful number of convalescent serum from severe patients using print, either in the 50 or in the 80?

第二個問題是關於第一階段/第二階段數據更新，希望是在本月或下個月。那麼，我們是否會看到更多有意義的重症患者恢復期血清數量（無論是 50 份還是 80 份）？

So let me take those. I'm not sure we're going to see significantly additional data on convalescent plasma. We're going to look at that when we report out the Phase II. So I think it's premature for me just say one way or another.

所以讓我拿走那些。我不確定我們是否會看到有關恢復期血漿的大量額外數據。當我們報告第二階段時，我們將對此進行研究。所以我認為現在就我這樣說還為時過早。

Regarding your question on Phase III, I'll make two points. The primary analysis is just a number of cases. It's not really -- it's a slightly different method statistically, but you end up with the same place as I think what you're referring to as the Pfizer methodology. You will see the number of cases and then the split in those cases. And of course, we'll describe the time frame. In terms of counting those cases, you are correct in that the formal counting of cases where you want to see the distribution occurs 14 days after the booster shot. That's the definition of the primary endpoint.

關於你提到的第三階段問題，我想講兩點。初步分析只是一些案例。這並不是真的——從統計學上來說，這是一種略有不同的方法，但你最終得到的結果與我認為你所說的輝瑞方法相同。您將看到案例數量以及這些案例的拆分情況。當然，我們會描述時間範圍。就這些病例的計數而言，您是正確的，因為您希望看到分佈的病例的正式計數發生在加強注射後 14 天。這就是主要終點的定義。

There is, however, a secondary endpoint that we'll look at the totality of cases that emerge once people start the trial. And of course, I think that could be further supportive evidence, especially if infection rates are so high that, indeed, we start to see some cases even in the first 6 weeks.

然而，還有一個次要終點，我們將查看人們開始試驗後出現的全部病例。當然，我認為這可能是進一步的支持性證據，特別是如果感染率如此之高，以至於我們甚至在前六週就開始看到一些病例。

The case definition for us is symptomatic disease. Again, there may be some minor variations between sponsors. I'm not sure everybody is fully harmonized to the same definition. We've been very transparent with the exact definition of our endpoints so that people can draw their conclusions and comparisons. Over.

我們的病例定義是有症狀的疾病。同樣，贊助商之間可能存在一些細微的差異。我不確定每個人都完全同意相同的定義。我們對端點的確切定義非常透明，以便人們可以得出結論和比較。超過。

Our next question comes from the line of Cory Kasimov from JPMorgan.

我們的下一個問題來自摩根大通的科里·卡西莫夫。

Two from me as well. First one is on pricing. I appreciate all the thought and detail that went into your prepared comments on the value proposition this morning. But I guess what I'm wondering is if we see other companies out there currently agreeing to contracts with various governments with price points that appear to range from low single digits to nearly $20 per dose, doesn't that make it inherently more difficult for you to try to charge something materially higher than that?

我也有兩個。第一個是關於定價。我感謝您今天早上就價值主張准備的評論中所包含的所有想法和細節。但我想我想知道的是，如果我們看到其他公司目前同意與各國政府簽訂合同，其價格點似乎從低個位數到每劑近20 美元不等，這是否會讓它本質上變得更加困難你試圖收取比這高得多的費用嗎？

And then second question is probably for Tal. I'm wondering, how difficult is it to maintain the integrity of a Phase III blinded trial when you would suspect a large proportion of the mRNA-1273 treated patients are expected to get common vaccination adverse events like fever and other symptomatic -- or other systemic events where presumably that wouldn't happen with placebo? Does that matter much in the end in your view?

第二個問題可能是問塔爾的。我想知道，當你懷疑大部分接受 mRNA-1273 治療的患者預計會出現常見的疫苗接種不良事件（例如發燒和其他症狀或其他症狀）時，維持 III 期盲法試驗的完整性有多困難安慰劑可能不會發生的全身事件？您認為這最終重要嗎？

Cory, so it's Stéphane. I'll take the first one on pricing and then I'm sure Tal will take the PIII question. So I think like in any discussion, Cory, many factors go into arriving or not to an agreement. I would say, first, the totality of the data that is available at the time of the discussions, preclinical model, clinical data. Again, given also we have a platform, we have the possibility to share in the public information that has been shared before over kind of data set. So I think data is an important one because I do not think all products are equal. And as Tal said, we would, of course, learn much more with Phase III data in the fall.

科里，所以是斯蒂芬。我將回答關於定價的第一個問題，然後我確信塔爾將回答 PIII 問題。所以我認為，就像在任何討論中一樣，科里，達成協議與否會受到許多因素的影響。我想說，首先是討論時可用的數據總量、臨床前模型、臨床數據。同樣，鑑於我們也有一個平台，我們有可能分享之前通過某種數據集共享的公共信息。所以我認為數據很重要，因為我不認為所有產品都是平等的。正如塔爾所說，我們當然會在秋季通過第三階段的數據了解更多信息。

Another consideration of course is volume, as we indicated in our remarks. And then another factor that is important is time of payment. How is the risk distributed between another companies that. But as we discussed in our remarks, like us, I've started to make product at risk, not knowing if 1273, in our case, will be approved or not. And so I think -- and there are many more consideration as well. So I think when you look at the totality of the data, as we've shared, we have signed a number of agreements already for potential supply in the $32 to $34 range. As we also said, as volume will increase, we'll of course integrate that into the analysis. So we'll work with the market, but we also know what we have in term of product.

正如我們在評論中指出的那樣，另一個考慮因素當然是數量。另一個重要因素是付款時間。風險如何在其他公司之間分配。但正如我們在發言中所討論的，像我們一樣，我已經開始讓產品面臨風險，不知道 1273（就我們而言）是否會獲得批准。所以我認為——還有更多的考慮因素。因此，我認為，當您查看全部數據時，正如我們所分享的那樣，我們已經就 32 至 34 美元範圍內的潛在供應簽署了許多協議。正如我們還說過的，隨著數量的增加，我們當然會將其整合到分析中。因此，我們將與市場合作，但我們也知道我們在產品方面擁有什麼。

Tal, do you want to take the PIII question?

Tal，你想回答 PIII 問題嗎？

Yes. So Cory, it's an astute observation, and we and our partners at NIH have thought about this one long and hard. I think at the end of the day, you're right, especially after the second dose. First dose, probably people still won't know it. The second dose, people may intuit whether they've got the active one or not. I think the important piece here is that the end points are pretty hard endpoints in that I don't think that you're going to be less likely to report significant symptoms if you've got placebo or not and the measurement of a PCR test as a PCR test.

是的。科里，這是一項敏銳的觀察，我們和美國國立衛生研究院的合作夥伴對此進行了長期而深入的思考。我認為歸根結底，你是對的，尤其是在第二劑之後。第一劑，可能人們還不知道。在第二劑藥物中，人們可能會憑直覺判斷自己是否接種了活性藥物。我認為這裡重要的一點是終點是相當硬的終點，因為我認為無論是否服用安慰劑以及 PCR 測試的測量，您報告顯著症狀的可能性都不會降低作為 PCR 測試。

We have put in place measures to ensure that there's no sort of corks of the unblinding, for example. We're going to be testing the -- by PCR, everybody both on dose 1 and when they come in for the second dose just to make sure that if they do see some mild flu-like symptoms, they're clearly attributable to vaccine, or it is an infection, then we're not biasing by measuring more frequently in those that got the vaccine. I think beyond the first couple of days, I don't expect them to be significant symptoms in anybody. So I don't think there's going to be biasing of any testing.

例如，我們已採取措施確保不存在任何開盲事件。我們將通過 PCR 測試每個人在接種第一劑疫苗和接種第二劑疫苗時的情況，以確保如果他們確實出現一些輕微的流感樣症狀，那麼他們顯然是由疫苗引起的，或者它是一種感染，那麼我們不會通過對接種疫苗的人進行更頻繁的測量而產生偏見。我認為在最初的幾天之後，我預計它們不會對任何人產生明顯的症狀。所以我認為任何測試都不會有偏見。

In terms of the asymptomatics, we're going to look retrospectively anyway and call that based on serology, and everybody will get tested. So I think by making sure that all the objective measures are done on both arms at the same time points, I think we're -- we should be in pretty good shape here.

就無症狀者而言，無論如何我們都會回顧性地進行回顧，並將其稱為基於血清學的檢測，每個人都會接受檢測。因此，我認為通過確保所有客觀措施在同一時間點在雙臂上完成，我認為我們應該處於良好的狀態。

Our next question comes from Geoff Meacham from Bank of America.

我們的下一個問題來自美國銀行的傑夫·米查姆。

I just had a few. So what we've learned on the value of 1273 is that T cell responses are important as our antibody titers. And so when you look at the new data today for Zika or for CMV or really anything going forward, do you think you'll place more emphasis on optimizing T cell responses just with respect to the platform?

我只吃了一些。因此，我們從 1273 的值了解到，T 細胞反應與我們的抗體滴度一樣重要。因此，當您今天查看 Zika 或 CMV 或任何未來的新數據時，您是否認為您會更加重視針對平台優化 T 細胞反應？

And then just to follow-up on 1273 pricing. When you look at the Phase III data, is there a single element that you would say justifies differential pricing, be it T cell or B-cell or safety profile, things like that?

然後就是跟進1273的定價。當你查看 III 期數據時，是否有一個元素可以證明差別定價是合理的，無論是 T 細胞、B 細胞還是安全性等？

So let me take, Geoff, the first question and let Stéphane answer the second. I think a lot of hay has been made out of T cell responses. Look, T cells are near and dear to my heart being a medical oncologist. They're required to cure cancer. I don't -- I'm not quite sure they're as important to cure COVID-19 frankly. I think what they are is a measure of the quality of the response, so if you will, they -- the fact that we see the right kind of Th1 helper, I think makes everybody feel good about the antibody responses.

傑夫，讓我回答第一個問題，讓斯特凡回答第二個問題。我認為很多乾草都是由 T 細胞反應製成的。聽著，作為一名腫瘤內科醫生，T 細胞對我來說是最親近的。他們需要治愈癌症。坦白說，我不太確定它們對於治愈 COVID-19 是否同樣重要。我認為它們是反應質量的衡量標準，所以如果你願意的話，我們看到了正確的 Th1 輔助因子這一事實，我認為這讓每個人都對抗體反應感覺良好。

But at the end of the day, the best measure of the immune response you're getting is look at the ability to boost after a prime. That tells you that the immune -- even after 1 dose, once you get the boost, you can see the antibody levels come up quickly. They come up to high levels, they come up with good neutralizing activity, which is the best predictor that should you get infected, the immune system will trigger again in a similar manner, and that's how the immune system works.

但歸根結底，衡量您獲得的免疫反應的最佳指標是觀察免疫反應後的增強能力。這告訴您免疫 - 即使在註射一劑後，一旦您獲得加強，您就可以看到抗體水平迅速上升。它們達到高水平，產生良好的中和活性，這是最好的預測因子，如果您被感染，免疫系統將以類似的方式再次觸發，這就是免疫系統的工作原理。

I think we've had plenty of data from other infectious diseases demonstrating that whenever you try to find a correlative protection, and Merck had done that with ZOSTAVAX years ago and that's even a disease where you think T cells matter more, the correlate of protection comes up time and again being neutralizing antibody, not T cells. T cells are an adjunct sort of measure of the quality of the response when it comes to these kinds of viruses. And I think the totality of the data that we've seen with SARS-CoV-2 in terms of all the animal models, you can passively transfer antibodies and get protection.

我認為我們已經有大量來自其他傳染病的數據表明，每當你試圖尋找相關保護時，默克公司幾年前就用ZOSTAVAX 做到了這一點，甚至在你認為T 細胞更重要的疾病中，保護的相關性一次又一次出現的是中和抗體，而不是 T 細胞。當涉及到這類病毒時，T 細胞是一種輔助衡量反應質量的方法。我認為，從我們在所有動物模型中看到的 SARS-CoV-2 數據來看，您可以被動轉移抗體並獲得保護。

So I think that there's been a lot of variability on the T cell side in terms of people recording assays, and I think people are trying to read into the tea leaves and assume something about the quality of the response. But to me, that's a more distal measure of what matters when you've got the most obvious proximal measure of what we think is the correlate and the thing that will translate to benefit, which is in neutralizing antibodies.

因此，我認為在人們記錄檢測方面，T 細胞方面存在很大的差異，而且我認為人們正在嘗試解讀茶葉並對反應的質量做出一些假設。但對我來說，當你得到了我們認為的相關性和將轉化為益處的最明顯的近端測量值（即中和抗體）時，這是對重要因素的更遠端測量。

So it's a bit of a long-winded way of saying that I don't think it matters as much. And certainly, when you look at optimizing our platform, look, we know our platform is optimized to generate T cell responses. We've seen that in the cancer T cell space where we just do -- all we do is raise CD8-positive T cells by putting in concatenated C8-positive epitopes. We get some CD4s. But that is an innate function scientifically of the ability to translate the antigen from within the cell with an mRNA. So I don't think it would be fruitful to try and optimize to T cells. I don't know that it matters and I wouldn't know how to do that. And by the way, we already have something that seems to do that based on the fundamental science of what our platform is doing.

因此，這是一種有點囉嗦的說法，我認為這並不那麼重要。當然，當您考慮優化我們的平台時，我們知道我們的平台經過優化可以產生 T 細胞反應。我們已經看到，在癌症 T 細胞領域，我們所做的就是通過放入串聯的 C8 陽性表位來培養 CD8 陽性 T 細胞。我們得到一些 CD4。但這是從細胞內用 mRNA 翻譯抗原的能力的先天功能。所以我認為嘗試和優化 T 細胞不會有成效。我不知道這很重要，也不知道該怎麼做。順便說一句，我們已經有了一些基於我們平台所做的基礎科學的東西。

Let me stop here and transfer to Stéphane.

讓我在這裡停下來，轉乘斯特凡去。

Yes. Thanks, Tal. So on the Phase III pricing. So safety, of course, is really important. But I would say it's important for us, the sponsor, for the regulators, obviously. And that will be kind of an important consideration to look at the totality of the data, especially for approval of a product. So assuming a good safety profile here, we believe that one important parameter of course is efficacy because, again, I think efficacy has different dimension. There's efficacy that is important to reach herd immunity at the population level. But also efficacy, if you look at it in the eyes of whoever receive the vaccine because as you can appreciate, the vaccine with 50% efficacy or a vaccine with 90% efficacy will be very different on what it means to you potentially just statistically in term of you getting protection or not.

是的。謝謝，塔爾。那麼關於第三階段的定價。因此，安全當然非常重要。但我想說，這對我們、贊助商和監管機構來說顯然很重要。這將是查看整體數據的一個重要考慮因素，特別是對於產品的批准而言。因此，假設這裡有良好的安全性，我們認為一個重要參數當然是功效，因為我再次認為功效有不同的維度。功效對於在人群水平上實現群體免疫非常重要。還有功效，如果你從接種疫苗的人的角度來看待它，因為正如你所理解的，功效為 50% 的疫苗或功效為 90% 的疫苗對你的意義可能只是統計上的差異。您是否獲得保護的期限。

And then I will say the subpopulation. I mean of course, healthy adult is what has been mostly reported so far. It's a very important population, obviously. But we all look forward to looking at the data in the elderly. As we all know, as Stephen described again during the remarks, the elderly are very vulnerable to this virus. And so understanding antibody titer, understanding efficacy in the elderly, we believe, is going to be important.

然後我會說亞人群。當然，我的意思是，迄今為止報導最多的是健康成年人。顯然，這是一個非常重要的人群。但我們都期待看到老年人的數據。眾所周知，正如斯蒂芬在講話中再次描述的那樣，老年人非常容易感染這種病毒。因此，我們相信，了解抗體滴度、了解老年人的功效非常重要。

So diversity, we talk about the ethnic group. It has been widely reported that some ethnic groups are impacted very differently by the virus. And so getting an understanding of that through the study. As you know, we have paid a lot of attention, and we talked about it recently in one of our call, of all the effort that the team is going through to ensure a good representation across ethnic groups.

所以多樣性，我們談論種族群體。據廣泛報導，一些種族群體受到該病毒的影響截然不同。因此通過研究來了解這一點。如您所知，我們非常關注，我們最近在一次電話會議中談到了團隊為確保跨種族群體的良好代表性而付出的所有努力。

And then I would say comorbidity. It's also very important, again, because of who is being held the most by this virus to understand is there a difference for different comorbidity groups for different vaccines.

然後我會說合併症。這也非常重要，因為誰是這種病毒感染最多的人，了解不同的疫苗對於不同的合併症群體是否存在差異。

So as you can see, I mean, there's going to be a lot of pieces to the efficacy picture. Again, some public payers in some countries might be willing or not to pay for different efficacy for different efficacy group. The private market might have a very defined inclination. And in places where it's out of pockets, you will have [financial] people having also making very different type of decisions.

正如你所看到的，我的意思是，功效圖將包含很多部分。同樣，一些國家的一些公共付款人可能願意或不願意為不同功效組的不同功效付費。私人市場可能有非常明確的傾向。在資金短缺的地方，[財務]人員也會做出非常不同類型的決策。

The other dimension, of course, is duration of protection, which obviously will take time for all the vaccine manufacturers to really understand at large scale in a clinical setting. But as you heard us say, we believe, like many other health expert, that this virus is not going away. We believe there's going to be an endemic market once the pandemic is declared over by the WHO. Duration would be an important factor. As you can appreciate, if a vaccine provides 1-year protection versus 6 month, versus 2 years, versus 3 years, that will all play into the equation.

當然，另一個維度是保護的持續時間，這顯然需要時間讓所有疫苗製造商在臨床環境中真正大規模地理解。但正如您聽到我們所說的那樣，我們像許多其他健康專家一樣相信這種病毒不會消失。我們相信，一旦世界衛生組織宣布大流行結束，將會出現一個地方性市場。持續時間將是一個重要因素。正如您所理解的，如果疫苗提供 1 年保護，而不是 6 個月、2 年、3 年保護，那麼這一切都會發揮作用。

So those are some of the factors that we will carefully think about, again, both in the pandemic setting, where we said we will make sure that we price the product at a big discount to value, and in the endemic setting, when we look at all these different product performance and market forces to determine what we believe is the most optimal price for our product.

因此，這些是我們將再次仔細考慮的一些因素，無論是在大流行環境下，我們表示我們將確保我們的產品定價比價值有很大折扣，還是在流行環境下，當我們考慮時根據所有這些不同的產品性能和市場力量來確定我們認為產品的最佳價格。

Our next question comes from Hartaj Singh from Oppenheimer.

我們的下一個問題來自奧本海默的 Hartaj Singh。

Just a couple of quick questions off the topic of COVID-19 vaccine. One is, can you just go over quickly the CMV Phase III program, the initiation of the development? And when you'd expect that to readout and potential approval for that sort of product?

只是幾個與 COVID-19 疫苗主題無關的簡短問題。一是，您能否快速回顧一下CMV III期項目，即開發的啟動階段？您何時預計該產品會被讀出並獲得潛在批准？

And then secondly, in some of our calls with pulmonologists that treat cystic fibrosis, there seems to be a lot of excitement around mRNA therapy for treating cystic fibrosis patients. The belief right now is that it could only treat a minority of those patients, but our calls seem to suggest that it could treat a majority of the cystic fibrosis patients. Could you talk a little bit to that? And where exactly are you with the Vertex collaboration?

其次，在我們與治療囊性纖維化的肺科醫生的一些電話中，對於治療囊性纖維化患者的 mRNA 療法似乎有很多興奮。目前人們認為它只能治療少數患者，但我們的呼籲似乎表明它可以治療大多數囊性纖維化患者。你能談談這個嗎？您對 Vertex 合作的具體進展如何？

So let me start with the Phase III. I'll let Stéphane talk about the Vertex collaboration. The Phase III, as we had previously articulated, I don't think anything has changed. The trial should follow participants for at least a couple of years. It will probably take around 18 months to enroll. And then you wrap up the data. So that sort of gives you a sense of the overall duration. We're on track to start next year. I think. What should be obvious to everybody is once we have the Phase II data, it's going to require some regulatory interactions in the Phase II meeting and so forth. We had gotten feedback in the past from FDA about the primary end points, which I think reassured us that it was feasible because we're looking to prevent primary infection in women of childbearing age, not directly looking at outcomes in babies, at least not as part of the Phase III program.

讓我從第三階段開始。我會讓 Stéphane 談談 Vertex 合作。正如我們之前所闡述的，第三階段我認為沒有任何變化。試驗應該跟踪參與者至少幾年。註冊可能需要大約 18 個月的時間。然後你打包數據。這樣你就可以了解整個持續時間。我們有望從明年開始。我認為。每個人都應該清楚的是，一旦我們獲得了第二階段的數據，就需要在第二階段會議等中進行一些監管互動。我們過去曾從 FDA 獲得過關於主要終點的反饋，我認為這讓我們確信這是可行的，因為我們正在尋求預防育齡婦女的原發感染，而不是直接觀察嬰兒的結果，至少不是作為第三階段計劃的一部分。

That being said, obviously, it will require much more detailed discussions with them on the Phase III design and the dose and alignment with them prior to start of the Phase III. So I hope that gives you some additional color.

話雖如此，顯然，在第三階段開始之前，需要與他們就第三階段的設計、劑量和調整進行更詳細的討論。所以我希望這能給你一些額外的色彩。

I can tell you, my sense on Vertex. As a scientist, I'm super excited by the potential for mRNA to not be limited by any particular mutation just from the fundamental signs of it. But I'll let Stéphane speak to the overall status of the collaboration. Over.

我可以告訴你，我對 Vertex 的感覺。作為一名科學家，我對 mRNA 不受任何特定突變的限制（僅從其基本跡象來看）的潛力感到非常興奮。但我會讓 Stéphane 談談合作的總體狀況。超過。

I'll let maybe Stephen talk about the view and his team doing all the work.

我會讓斯蒂芬談論這個觀點和他的團隊所做的所有工作。

I think Stephen had to jump off our call.

我認為斯蒂芬不得不中斷我們的通話。

Sorry. Thank you. So on Vertex, so as we've communicated, I think it was in the Q1 call, Vertex decided to expand the collaboration with Moderna on CF. The joint teams' discovery have done a really remarkable job in the last few years in term of delivery. As you can imagine, given you know as well, making the CFTR mRNA is not that complicated given all the things we have done and the current state of the platform and the technology. It is obviously the challenge entirely in delivery. We look forward to sharing some data soon.

對不起。謝謝。因此，在 Vertex 上，正如我們所溝通的，我認為在第一季度的電話會議中，Vertex 決定擴大與 Moderna 在 CF 上的合作。聯合團隊的發現在過去幾年中在交付方面做得非常出色。正如您所想像的，鑑於您也知道，考慮到我們所做的所有事情以及平台和技術的當前狀態，製作 CFTR mRNA 並不那麼複雜。顯然，這完全是交付方面的挑戰。我們期待盡快分享一些數據。

Again, it's a partnership. So we need, of course, to align with Vertex on what do we believe is the right timing. But as Tal said, the teams on both sides, I think, Vertex and Moderna, are very excited about the progress, about the possibility of what it will mean for patients. And as we discussed before, if we can find the technology to deliver safely into the lungs, mRNA, obviously, we will be able to use that for other diseases of the lung. And just to remind everybody, the Vertex collaboration is focused on the CFTR gene, and so the other applications will belong to Moderna from a commercial standpoint.

再說一次，這是一種夥伴關係。因此，我們當然需要與 Vertex 就我們認為正確的時機保持一致。但正如 Tal 所說，我認為 Vertex 和 Moderna 雙方的團隊都對這一進展以及這對患者意味著什麼的可能性感到非常興奮。正如我們之前討論的，如果我們能夠找到將 mRNA 安全地輸送到肺部的技術，顯然我們將能夠將其用於其他肺部疾病。需要提醒大家的是，Vertex 的合作重點是 CFTR 基因，因此從商業角度來看，其他應用程序將屬於 Moderna。

Next question comes from Alan Carr from Needham & Company.

下一個問題來自 Needham & Company 的 Alan Carr。

Just following on the theme of programs other than COVID-19. You mentioned before that enrollment in few of these programs is still paused or suspended because of COVID-19. I'm just kind of wondering if -- and if you're able to still get prioritized and move forward some of your other programs, such as the rare disease programs. Do you feel like you can still keep your eye on the ball in terms of the rest of the non-COVID pipeline at Moderna?

只是關注除 COVID-19 之外的節目主題。您之前提到過，由於 COVID-19，其中一些項目的註冊仍處於暫停或暫停狀態。我只是想知道您是否仍然能夠優先考慮並推進一些其他項目，例如罕見疾病項目。您是否覺得您仍然可以密切關注 Moderna 的其他非新冠疫情管道？

This is Tal. Let me maybe take a stab at that. I think the answer is absolutely yes. And I think it's evidenced by the progress that we continue to show for the rest of our pipeline. We've expanded the development team quite significantly to go after the COVID-19 vaccine. So that I think we've got very capable teams that are pushing everything else. The fact that we continue to enroll in oncology, it's seen a little bit of a slowdown similar to others, and we -- it really depends on the individual center status of who's enabled and when to treat patients.

這是塔爾。也許讓我嘗試一下。我認為答案是絕對肯定的。我認為我們在其餘產品線中繼續取得的進展就證明了這一點。我們大幅擴大了開發團隊，以開發 COVID-19 疫苗。所以我認為我們擁有非常有能力的團隊來推動其他一切。事實上，我們繼續在腫瘤學領域註冊，與其他領域類似，我們看到了一些放緩，這實際上取決於各個中心的狀態，即誰可以使用以及何時治療患者。

I think on the rare disease, not only is our eye on the ball, I think we've -- as we had alluded to in the past, we're actually using the time to kind of step back and engage deeper with both investigators and patients and advocates to make sure that when we do restart those programs, because the kids can finally come back in, those programs are better optimized so that they can -- we can perform better in terms of recruitment and analysis of data on the study.

我認為，在這種罕見疾病上，我們不僅要密切關注，而且正如我們過去提到的那樣，我們實際上是在利用這段時間退後一步，與兩位調查人員進行更深入的接觸以及患者和倡導者，以確保當我們重新啟動這些計劃時，因為孩子們終於可以回來了，這些計劃得到了更好的優化，以便他們能夠——我們可以在研究的招募和數據分析方面表現更好。

So we're continuing to execute across all the fronts. And I think you'll see us, hopefully the pandemic recedes, or [recenters], figure out how to -- despite PPE and social distancing to continue or restart clinical activities, then we should come back online across the board. Over.

因此，我們將繼續在各個方面執行。我想你們會看到我們，希望疫情消退，或者[重新集中]，弄清楚如何——儘管有個人防護裝備和社交距離，繼續或重新啟動臨床活動，然後我們應該全面恢復在線。超過。

Yes. And maybe just to add to Tal's important comment. When things started to look bad from a global basis in terms of the spread of SARS-CoV-2, we spent quite a long time, I would say, in the February time frame, with the Board and with the team to think about how do we structure the company, how do we resource a company, to Tal's point, so that we can do both. It was very clear that a lot of focus and energy was going to be required to march at a very fast pace without compromise to safety for 1273. But at the same time, Moderna has always been a platform company. It has always been about managing risk through a very diverse pipeline across different therapeutic areas across different modalities or technology for those on the call that are not used to Moderna. And so it was really important for us given the inherent risk of developing a product like 1273. Again, we feel much better now given the data we have seen, but I'm talking back in February.

是的。也許只是為了補充塔爾的重要評論。當 SARS-CoV-2 的傳播從全球範圍來看情況開始變得糟糕時，我想說，在 2 月份的時間範圍內，我們花了相當長的時間與董事會和團隊一起思考如何按照塔爾的觀點，我們如何構建公司，如何為公司提供資源，以便我們能夠做到這兩點。很明顯，1273 需要大量的注意力和精力才能在不影響安全的情況下以非常快的速度前進。但與此同時，Moderna 一直是一家平台公司。對於那些不習慣 Moderna 的人來說，它始終是通過跨不同治療領域、不同模式或技術的非常多樣化的管道來管理風險。因此，考慮到開發 1273 這樣的產品的固有風險，這對我們來說非常重要。同樣，鑑於我們看到的數據，我們現在感覺好多了，但我是在 2 月份談論的。

And so we couldn't quite a large number of very experienced development professionals in clinical, regulatory, clinical operation to be able to actually do both. That was one of our big challenge. And I have to say the team has really done a remarkable job to both push 1273 as safe as we can, as hard as we can, because we know that every day those matter, and at the same time, continue to execute on the pipeline. It has been very challenging given the lockdown, given our focus on safety. Some of the studies were easier to keep rolling. Some of the studies, because involving children we wanted to make sure, especially with children with very severe disease, that we didn't take the risk to expose them to infection by going to clinical trial sites or their caregiver, their family. And so we have not laid down an inch on the focus on the pipeline outside of COVID.

因此，我們無法在臨床、監管和臨床操作方面擁有大量經驗豐富的開發專業人員，從而能夠真正做到這兩點。這是我們面臨的重大挑戰之一。我不得不說，團隊確實做了出色的工作，盡可能安全、盡我們所能地推動 1273，因為我們知道這些每一天都很重要，同時繼續在管道上執行。考慮到封鎖，考慮到我們對安全的關注，這非常具有挑戰性。有些研究更容易繼續進行。有些研究涉及兒童，特別是患有非常嚴重疾病的兒童，我們希望確保我們不會冒著去臨床試驗地點或他們的護理人員、他們的家人而使他們受到感染的風險。因此，我們還沒有對新冠疫情之外的管道進行任何關注。

Our next question comes from George Farmer from BMO Capital Markets.

我們的下一個問題來自 BMO 資本市場的 George Farmer。

Quite struck by the fact that neutralizing antibody titers don't really seem to emerge until after the second boost, whereas antibodies in general seem to be elicited after the first injection. How do you think about this? I mean it seems to be across the board not just with your vaccine, but with these other vaccines. And importantly, how would such patients be treated in the Phase III should they come down with COVID, say, after the first injection because of not having the sufficient titer going into the second injection?

令人震驚的是，中和抗體滴度似乎直到第二次加強後才真正出現，而抗體通常似乎是在第一次注射後引發的。您對此有何看法？我的意思是，這似乎不僅適用於您的疫苗，也適用於其他疫苗。重要的是，如果這些患者在第一次注射後因為第二次注射沒有足夠的滴度而感染了新冠病毒，那麼在第三階段將如何治療？

Thanks, George, it's Tal. Yes, it is interesting. I think it kind of speaks to basic immunology, which is if your immune system thinks that it can clear an infection easy, it doesn't try too hard. If you come back later and basically show that, no, the infection isn't gone, then it tries harder. And that's usually manifest with affinity maturation improvements in the antibody's qualities as well as the absolute titers. And so I suspect what you're seeing is a subtle manifestation of that.

謝謝，喬治，我是塔爾。是的，這很有趣。我認為這有點涉及到基礎免疫學，也就是說，如果你的免疫系統認為它可以輕鬆清除感染，它就不會太努力。如果你稍後回來並基本上表明，不，感染沒有消失，那麼它會更加努力。這通常通過抗體質量和絕對滴度的親和力成熟改善來體現。所以我懷疑你所看到的是這種微妙的表現。

Now the question is though, what happens after just the prime? Yes, you don't have neutralizing antibodies, but clearly, the immune system now reacts differently once it sees the antigen because you get the boost. And so it's an interesting question. Well what happens if the boost happens not with the vaccine, but with the natural infection? I would suspect based on sort of first principles, that you should see some benefit, probably, not the full benefit you would see if you get infected after the boost, but just by nature of the boosting, you would expect that an infection would also boost in the sense that the immune response would react quicker and more vigorously. And maybe you won't prevent infection and maybe you won't even prevent a disease, but hopefully, you would prevent the more severe manifestation of disease. Because disease, at least as we understand it in the first phase here, is a balance between your immune response and clearing the infection.

現在的問題是，在素數之後會發生什麼？是的，你沒有中和抗體，但顯然，一旦免疫系統看到抗原，就會做出不同的反應，因為你得到了增強。這是一個有趣的問題。那麼，如果增強效果不是通過疫苗而是通過自然感染髮生的，會發生什麼？我懷疑基於某種首要原則，你應該會看到一些好處，可能不是你在加強後感染時會看到的全部好處，但僅僅根據加強的性質，你會期望感染也會增強是指免疫反應會反應得更快、更有力。也許你無法預防感染，甚至可能無法預防疾病，但希望你能夠預防更嚴重的疾病表現。因為疾病，至少按照我們在第一階段的理解，是免疫反應和清除感染之間的平衡。

So it will be very interesting, I think, both for us and for other platforms that use a prime boost to do that secondary analysis of understanding whether we've seen any cases in that first month or 6 weeks and what the distribution of cases are between placebo, and you're treated.

因此，我認為，對於我們和其他使用主要提升進行二次分析的平台來說，這將非常有趣，以了解我們在第一個月或六週內是否看到了任何病例以及病例的分佈情況介於安慰劑和治療之間。

The last piece I'd say that I think also gives me some hope here is the nonhuman primate, where a single dose in the nonhuman primate can -- or at least the mouse models. The experiment with the nonhuman primate is ongoing. But in the mouse models, we clearly see that even though you don't see -- you don't measure the neutralizing antibodies just yet, you are already able to limit viral or aggregate viral application in the lungs. And so I think that gives you a sort of immunological readout on the phenomenon I'm describing. Over.

我想說的最後一篇文章也給了我一些希望，那就是非人類靈長類動物，在非人類靈長類動物中，或者至少在小鼠模型中，單劑量就可以。非人類靈長類動物的實驗正在進行中。但在小鼠模型中，我們清楚地看到，即使你還沒有看到——你還沒有測量中和抗體，你已經能夠限制病毒或聚集病毒在肺部的應用。所以我認為這可以讓你對我所描述的現像有一種免疫學的解讀。超過。

Okay. And then along those lines, do we have a view on durability yet? I mean following these -- following both the nonhuman primates and maybe the mice. If they live long enough, do you have a sense for how durable the vaccine effect could be?

好的。那麼沿著這些思路，我們對耐久性有看法嗎？我的意思是跟踪這些——跟踪非人類靈長類動物，也許還有老鼠。如果他們活得足夠長，你知道疫苗效果能有多持久嗎？

Yes. I do not. I would make 2 points on that. First, I don't think any of us yet understands durability. What is emerging is that if you have a mild infection, you're more likely to have lower level of antibodies and therefore likely to wane. That kind of goes with the quality of the immune response that I described previously. It's also -- I mean let's not mistake the ability to measure antibodies over time as the sine qua non of having a memory and immune response, right? Otherwise, by the time you were my age, you'd be walking around with your blood thick and clotting with antibodies against every infection you've ever seen. And yet, I am immune to many things that you are not going to necessarily see high levels of neutralizing antibodies in my blood. It's more about the memory B cells and the persistence. I think that initial level of neutralizing antibodies is what gives us the confidence that we've got the right quality of the response and the magnitude is at high or higher than what you can see with disease with real infection in convalescent plasma.

是的。我不。我想就此提出兩點。首先，我認為我們中沒有人了解耐久性。正在出現的情況是，如果您感染輕微，您的抗體水平很可能較低，因此抗體水平可能會下降。這與我之前描述的免疫反應的質量相一致。我的意思是，我們不要將隨著時間的推移測量抗體的能力誤認為是具有記憶和免疫反應的必要條件，對吧？否則，當你到了我這個年紀的時候，你的血液就會變得粘稠，並且會凝結出針對你所見過的每種感染的抗體。然而，我對許多東西免疫，你不一定會在我的血液中看到高水平的中和抗體。更多的是關於記憶 B 細胞和持久性。我認為中和抗體的初始水平使我們有信心，我們已經獲得了正確的反應質量，並且其強度高於或高於恢復期血漿中真正感染的疾病。

Now all that being said, I think it's obviously reassuring to see the quality of a response by maintaining high neutralizing antibodies. I think if you look at what the platform is able to induce, it's pretty evident from the CMV data I described earlier this morning that, certainly, in that instance, with a third boost at 6 months, look out to a year, and you see levels that are still higher than what you had targeted. I think as it all boils down to the utilization in the context of a pandemic here, if what we have is 12 months of durability, I think that's a great starting point for us to start protecting the population. And we'll worry about what happens in year 2, 3 and 4 when we get to 2022, 2023, on the other side of this pandemic. Over.

話雖如此，我認為通過維持高中和抗體來看到反應的質量顯然令人放心。我認為，如果你看看這個平台能夠帶來什麼，從我今天早上早些時候描述的CMV 數據中可以明顯看出，當然，在這種情況下，在6 個月時進行第三次提升，展望一年，你看到的水平仍然高於您的目標。我認為，這一切都歸結為在大流行背景下的利用，如果我們擁有 12 個月的耐用性，我認為這是我們開始保護人口的一個很好的起點。當我們到 2022 年、2023 年，即這場大流行的另一邊時，我們會擔心第 2 年、第 3 年和第 4 年會發生什麼。超過。

Our last question comes from Mani Foroohar from SVB Leerink.

我們的最後一個問題來自 SVB Leerink 的 Mani Foroohar。

A couple for me. One quick one from an investor. Could you lay out the economics you guys received on any commercialized vaccine? How to think about percentages paid out to academic partners? And any NIH commercial economic interest, et cetera? Just breaking it out as we try to understand what unit margin might be.

給我一對。一位投資者的快速報導。您能否列出從任何商業化疫苗中獲得的經濟效益？如何考慮支付給學術合作夥伴的百分比？還有 NIH 的任何商業經濟利益嗎？當我們嘗試了解單位利潤可能是多少時，將其分解。

And then secondarily, as we look at pricing, it's been commented by a couple of people here, a couple of analysts regarding pricing in the low single digits to up to just below $20, for example, in larger volume contracts. It sounds like we should think as somewhere in that range as par for larger contracts for you guys during the pandemic. But as you talk about the endemic environment and potentially higher pricing, could you lay out how you expect to realize that pricing in a setup where demand will likely decline as the severity of COVID-19's impact globally is reduced during an endemic versus a pandemic period, in a setting where perhaps a half dozen or more vaccines being commercialized by large established players with commercial experience in tender markets such as these will be actively competing on price and volume? So if you could lay out how you expect to substantially increase your realized price in a setting of increased competition, increased supply and reduced demand, that would be really helpful.

其次，當我們考慮定價時，這裡的一些人、幾位分析師對定價從低個位數到略低於 20 美元（例如，大批量合同）發表了評論。聽起來我們應該考慮在這個範圍內的某個地方作為大流行期間為你們提供更大合同的標準。但是，當您談到地方性流行環境和潛在的更高定價時，您能否闡述一下，在地方性流行期間與大流行期間，隨著COVID-19 全球影響的嚴重程度降低，需求可能會下降，您期望如何實現定價，在這種情況下，在招標市場上擁有商業經驗的大型企業正在商業化的疫苗可能有六種或更多，這些疫苗將在價格和數量上積極競爭？因此，如果您能列出在競爭加劇、供應增加和需求減少的情況下預計如何大幅提高實際價格，那將非常有幫助。

Thank you. This is Stéphane. So this first one is going to be quick because we are not disclosing unit margin per product.

謝謝。這是史蒂芬。因此，第一個將會很快，因為我們不會披露每種產品的單位利潤率。

On the endemic market, clearly, as we said in our remarks, the competitive dynamics are going to be important. We continue to believe that when you look at the totality of the data, not only across 1273, but across 1273 today that's public, and they're on the platform, that efficacy is going to be an important parameter. We've hired people and we'll continue to have people in the commercial world that comes from large established vaccine players who have relationship with governments, who have relationship with people in the channel. And so we believe that we should be able to establish a good commercial presence based on the performance of the product.

正如我們在評論中所說，顯然，在流行市場上，競爭動態將非常重要。我們仍然相信，當你查看全部數據時，不僅是 1273 個數據，而且是今天公開的 1273 個數據，而且它們都在平台上，功效將成為一個重要參數。我們已經僱用了人員，並且我們將繼續在商業界僱用來自大型疫苗生產商的人員，他們與政府有關係，與渠道中的人員有關係。所以我們相信我們應該能夠根據產品的性能建立良好的商業形象。

Great. And as a follow-up, when you talked -- so a couple of things about the CD8 T cell response, T cell biology. Just to clear up, the comment that you've -- that across your platform, you've shown effective T cell response, that was directed regarding constructs in your cancer portfolio, right? And not at this particular vaccine where we haven't seen a CD8 T cell response of any measurable level as described in your nonhuman primate or human disclosures thus far. You were talking about the cancer vaccines, right? You weren't talking about any prophylactic vaccines, so I guess, CD8 T cell response here?

偉大的。作為後續行動，當您談到一些關於 CD8 T 細胞反應和 T 細胞生物學的事情時。只是為了澄清一下，您的評論 - 在您的平台上，您已經表現出有效的 T 細胞反應，這是針對您的癌症組合中的結構的，對吧？而對於這種特定的疫苗，我們還沒有看到任何可測量水平的 CD8 T 細胞反應，正如您迄今為止在非人類靈長類動物或人類披露中所描述的那樣。你剛才談論的是癌症疫苗，對吧？你沒有談論任何預防性疫苗，所以我猜，CD8 T 細胞反應在這裡？

So this is Tal. That is correct, although I have to go back because we did disclose some T cells for CMV. I don't recall whether they were CD8 or just CD4, frankly, off the top of my head. Yes.

這就是塔爾。這是正確的，儘管我必須回去，因為我們確實披露了一些用於 CMV 的 T 細胞。我不記得它們是 CD8 還是只是 CD4，坦率地說，我一時想不起來。是的。

I show no further questions in the queue. At this time, I'd like to turn the call over to Stéphane Bancel, CEO, for closing remarks.

我在隊列中沒有顯示任何其他問題。現在，我想將電話轉給首席執行官 Stéphane Bancel，讓其致閉幕詞。

Well thank you very much, everybody, for joining today. Stay safe. And we'll speak soon.

非常感謝大家今天的加入。注意安全。我們很快就會說話。

Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

謝謝。女士們、先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。