莫德納 (MRNA) 2020 Q3 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.

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。

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

此時，我會將電話轉給 Moderna 投資者關係主管 Lavina Talukdar。請繼續。

Thank you. Good morning, everyone, and welcome to Moderna's Third Quarter 2020 Conference Call to discuss financial results and business updates. You can access the press release issued this morning as well as the slides that we'll be reviewing by going to the Investors section of our website.

謝謝。大家早上好，歡迎參加 Moderna 2020 年第三季度電話會議，討論財務業績和業務動態。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 provisions of the Private Securities Litigation Reform Act of 1995. Please see Slide 2 of the accompanying presentation and our SEC filings for important risk factors that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements. We undertake no obligation to revise the information or provide -- provided on this call as a result of new information or future results or development.

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修改本次電話會議中提供的信息或提供的義務。

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 and your loved ones are in good health and remain safe. Thank you for joining our Q3 business update conference call. I will start with reviewing key highlights.

謝謝你，拉維娜。大家早上好或者下午好。我希望你們所有人和你們所愛的人都身體健康並保持安全。感謝您參加我們的第三季度業務更新電話會議。我將首先回顧一下主要亮點。

I would like to focus on 3 topics: first, our COVID-19 vaccine; second, our broader development pipeline; and finally, key financials.

我想重點談三個話題：第一，我們的 COVID-19 疫苗；第二，我們更廣泛的開發渠道；最後是關鍵財務數據。

As many of you know, we completed enrollment of our Phase III COVE study for mRNA-1273. 30,000 participants have been enrolled in the study, 37% of whom are from diverse communities. Tal will give you some details in a few minutes. We are grateful for participants in the study and for principal investigators.

正如你們許多人所知，我們已完成 mRNA-1273 的 III 期 COVE 研究的註冊。該研究已有 30,000 名參與者參與，其中 37% 來自不同社區。塔爾將在幾分鐘內為您提供一些詳細信息。我們感謝該研究的參與者和主要研究人員。

I would like to also thank PPD and NIH for a great job and collaboration.

我還要感謝 PPD 和 NIH 所做的出色工作和合作。

It is very important to the Moderna team that we have a high bar for quality and transparency to ensure the public has trust in COVID-19 vaccine. We have reported weekly enrollment progress of the COVE study and have reported weekly enrollment numbers from diverse communities. While we are not happy with the representation of these diverse communities, given the high burden of disease in these populations, we decided to slow down the overall COVE study enrollment process in order to recruit more people from diverse communities.

對於 Moderna 團隊來說，非常重要的是，我們對質量和透明度有很高的要求，以確保公眾對 COVID-19 疫苗的信任。我們報告了 COVE 研究的每週註冊進度，並報告了來自不同社區的每週註冊人數。雖然我們對這些不同社區的代表性並不滿意，但考慮到這些人群的疾病負擔很高，我們決定放慢整個 COVE 研究的招募過程，以便從不同社區招募更多的人。

As you can imagine, it was not an easy decision to slow down, but it was the right decision. We signed the biopharma pledge to not submit for regulatory approval for mRNA-1273 until we have adequate safety and efficacy data.

正如你可以想像的那樣，放慢速度並不是一個容易的決定，但卻是一個正確的決定。我們簽署了生物製藥承諾，在獲得足夠的安全性和有效性數據之前，不會提交 mRNA-1273 的監管批准。

We were also the first company to file the full and redacted version of our Phase III protocol online to ensure clinicians around the world could see in full transparency how the COVE study is being run. We were pleased to set the standard and have others in the industry follow early.

我們也是第一家在線提交完整且經過編輯的 III 期試驗方案版本的公司，以確保世界各地的臨床醫生能夠完全透明地了解 COVE 研究的進行情況。我們很高興制定了標準，並讓業內其他人儘早效仿。

We continue to expect our first interim analysis to read out in November. The independent Data Safety Monitoring Board, or DSMB, will carry out this interim analysis and then inform Moderna. We should have a post second dose 2-month safety follow-up after the second vaccination of a 15,000 median participants in the second half of November.

我們仍然預計我們的第一份中期分析將於 11 月公佈。獨立數據安全監控委員會 (DSMB) 將進行中期分析，然後通知 Moderna。在 11 月下半月對 15,000 名中位數參與者進行第二次疫苗接種後，我們應該進行第二次疫苗接種後為期 2 個月的安全性隨訪。

As many of you know, this is what the U.S. FDA has asked as part of a EUA submission in their latest guideline published ahead of October 22 VRBPAC meeting. We are working closely with the U.S. FDA to file Chemistry, Manufacturing, and Controls, or CMC, components as soon as they are available to ensure CMC is not on the critical path to an EUA approval.

正如許多人所知，這是美國 FDA 在 10 月 22 日 VRBPAC 會議之前發布的最新指南中提出的 EUA 提交要求的一部分。我們正在與美國 FDA 密切合作，一旦化學、製造和控制（CMC）組件可用，就會立即提交這些組件，以確保 CMC 不會成為獲得 EUA 批准的關鍵路徑。

In addition to the ongoing dialogue with the U.S. FDA, we have announced rolling submissions for mRNA-1273 in the U.K. and Canada and received confirmation of eligibility for submission of marketing authorization application to the EMA for the EU.

除了與美國 FDA 持續對話外，我們還宣佈在英國和加拿大滾動提交 mRNA-1273，並收到了向歐盟 EMA 提交營銷授權申請的資格確認。

We are very pleased to announce this morning that we have signed a partnership with -- in Japan with Takeda, for an order of 50 million doses for the Ministry of Health, Labour and Welfare of Japan.

今天早上我們非常高興地宣布，我們已與日本武田公司簽署了合作夥伴關係，為日本厚生勞動省訂購 5000 萬劑疫苗。

In the third quarter, we have received $1.1 billion of cash payments from governments around the world, and those are accounted in our financials as deferred revenues.

第三季度，我們從世界各國政府收到了 11 億美元的現金付款，這些現金在我們的財務報表中計入遞延收入。

Let me now turn to our broader pipeline. We announced at R&D Day in September, the positive Phase II readout for mRNA-1647, or CMV vaccine. We are on track to start the pivotal Phase III registration study for CMV in 2021. I will refer you to our April Vaccine Day presentation in which we communicated that we believe our CMV vaccine has a potential for annual peak sales between $2 billion and $5 billion. There is no approved vaccine against CMV, and it is the #1 cause of birth defect in the U.S. and in developed world. Moderna owns global rights to CMV 1647.

現在讓我談談我們更廣泛的管道。我們在 9 月份的研發日宣布 mRNA-1647（即 CMV 疫苗）的 II 期試驗結果呈陽性。我們有望在2021 年開始關鍵的CMV III 期註冊研究。我將向您推薦我們的四月疫苗日演示文稿，其中我們表示，我們相信我們的CMV 疫苗的年度峰值銷售額有可能達到20 億至50億美元。目前還沒有批准的針對 CMV 的疫苗，它是美國和發達國家出生缺陷的第一大原因。 Moderna 擁有 CMV 1647 的全球權利。

Our intratumoral OX40L ligand program, that many of you have heard about at our recent R&D Day, is now doing patients in the Phase II expansion study. In rare disease, start-up activities under an amended protocol for Phase I propionic acidemia, or PA, study are underway. All of our pipeline programs that we're enrolling and dosing patients also continue and are ongoing.

我們的瘤內 OX40L 配體項目，很多人在我們最近的研發日上都聽說過，現在正在 II 期擴展研究中對患者進行治療。在罕見疾病方面，根據修訂後的 I 期丙酸血症（PA）研究方案啟動活動正在進行中。我們正在招募和給患者用藥的所有管道項目也仍在繼續。

Let me finish this slide with a few words about financials. David will go through the financial numbers in a few minutes, but I wanted to share a few thoughts. As I mentioned earlier, we reported this morning that we booked $1.1 billion of deferred revenues in Q3 for supply agreements for mRNA-1273. This cash has been received by the company. This cash received have enabled the company to generate $893 million of cash flow provided by operating activities in the third quarter after investment of approximately $300 million in the business.

讓我用幾句關於財務的話來結束這張幻燈片。大衛將在幾分鐘內瀏覽財務數據，但我想分享一些想法。正如我之前提到的，我們今天早上報告說，我們在第三季度為 mRNA-1273 的供應協議預訂了 11 億美元的遞延收入。該現金已由公司收到。在對該業務進行了約 3 億美元的投資後，收到的現金使公司第三季度的經營活動產生了 8.93 億美元的現金流。

If you turn to Slide 4, I am pleased to report that this is the first quarter in the company history in which we reported positive cash flow provided by operating activities coming from product supply agreement. It has been 10 years after inception and after investing billions of dollars in science and product development. Thank you to all our employees, scientists, of course, to our investors and to all of you that have believed in Moderna.

如果您翻到幻燈片 4，我很高興地報告，這是公司歷史上第一個季度，我們報告了來自產品供應協議的經營活動提供的正現金流。該公司成立已有 10 年，在科學和產品開發方面投入了數十億美元。感謝我們所有的員工、科學家，當然還有我們的投資者以及所有相信 Moderna 的人。

Let me turn to Slide 5 for my closing remarks. As a snapshot of Moderna, in October 2020, we have accomplished a lot and continue to have a broad pipeline that continues to progress well. We have fully enrolled Phase III program with mRNA-1273. We now have 4 Phase II trials with CMV, personalized cancer vaccine, VEGF with AstraZeneca and now OX40 ligand, 7 ongoing Phase I programs and 12 positive Phase I studies.

讓我轉向幻燈片 5 作結束語。作為 Moderna 的一個快照，在 2020 年 10 月，我們已經取得了很多成就，並且繼續擁有廣泛的管道，並且繼續進展順利。我們已經全面註冊了 mRNA-1273 的 III 期項目。我們現在有 4 個關於 CMV、個性化癌症疫苗、阿斯利康 VEGF 以及現在的 OX40 配體的 II 期試驗，7 個正在進行的 I 期項目和 12 項積極的 I 期研究。

Our vaccine franchise has 6 programs in development addressing the major unmet needs. We have 5 immuno-oncology programs in the clinic, 4 programs in rare disease and 2 programs in autoimmune disease.

我們的疫苗特許經營權有 6 個正在開發的項目，旨在解決主要的未滿足需求。我們在臨床上有5個免疫腫瘤學項目、4個罕見疾病項目和2個自身免疫性疾病項目。

Our foundations have never been stronger with 32,000 participants and patients in our trials. We have now over 1,200 employees. We have an international manufacturing capacity and capabilities with our partner, Lonza, ROVI and Catalent. And we have strategic partnerships with companies like Merck, AstraZeneca and Vertex.

我們的試驗擁有 32,000 名參與者和患者，因此我們的基礎變得更加堅實。我們現在有超過 1,200 名員工。我們與合作夥伴 Lonza、ROVI 和 Catalent 一起擁有國際製造能力。我們與默克 (Merck)、阿斯利康 (AstraZeneca) 和福泰 (Vertex) 等公司建立了戰略合作夥伴關係。

At the end of September, we have a strong balance sheet of $4 billion. I am very proud of what we have accomplished so far and where we stand as a company. The next few weeks and months are going to be quite historic for Moderna.

截至 9 月底，我們的資產負債表強勁，達 40 億美元。我對我們迄今為止所取得的成就以及我們作為一家公司的地位感到非常自豪。接下來的幾周和幾個月對於 Moderna 來說將是具有歷史意義的。

I will now turn it over to Tal to talk about clinical updates. Tal?

我現在將把它交給塔爾來談論臨床更新。塔爾？

Thank you, Stéphane, and good morning, everybody. Let me give you a quick overview of our pipeline progress and starting with our COVID vaccine. The Phase II study, looking at safety and immunogenicity in 600 participants is ongoing. Dosing has been completed, but we remain blinded while the final immunological testing is being conducted. Once we have the results, we will show them.

謝謝你，斯特凡，大家早上好。讓我向您快速概述一下我們的管道進展情況，並從我們的新冠疫苗開始。 II 期研究正在進行中，該研究針對 600 名參與者進行了安全性和免疫原性研究。給藥已經完成，但在進行最終免疫學測試時我們仍然處於失明狀態。一旦我們得到結果，我們就會向他們展示。

As a reminder, the safety data from this trial have, of course, been shared with regulators prior to the start of our Phase III COVE study. That is now fully enrolled, and I will share some details shortly.

提醒一下，當然，在我們的 III 期 COVE 研究開始之前，該試驗的安全數據已與監管機構共享。現在已經完全註冊，我將很快分享一些細節。

For our CMV vaccine, mRNA-1647, we shared positive Phase II data at our annual R&D Day in September, and the data enabled us to select the 100-microgram dose to take forward in our pivotal Phase III trial, which is expected to begin in 2021.

對於我們的 CMV 疫苗 mRNA-1647，我們在 9 月份的年度研發日分享了積極的 II 期數據，這些數據使我們能夠選擇 100 微克劑量來推進我們的關鍵 III 期試驗，該試驗預計將開始2021年。

For our Zika vaccine, we showed the positive Phase I results and are preparing for Phase II. On the pediatric front, I'm happy to announce that our hMPV/PIV3 Phase Ib age de-escalation study has resumed dosing toddlers aged 12 to 36 months following a pause that was related to COVID-19 disruptions. This is the first mRNA vaccine to be given to toddlers.

對於我們的寨卡疫苗，我們顯示出積極的第一階段結果，並正在為第二階段做準備。在兒科方面，我很高興地宣布，我們的 hMPV/PIV3 Ib 期年齡遞減研究在因 COVID-19 干擾而暫停後，已恢復對 12 至 36 個月大的幼兒進行給藥。這是第一種針對幼兒的 mRNA 疫苗。

In addition, the first cohorts of adult participants in the Phase I study of our RSV vaccine, mRNA-1345, has now been fully enrolled. As a reminder, this is also an age de-escalation study similar to the hMPV/PIV 3 study, and the plan is ultimately to also dose toddlers.

此外，我們的 RSV 疫苗 mRNA-1345 第一階段研究的第一批成人參與者現已全部入組。提醒一下，這也是一項類似於 hMPV/PIV 3 研究的年齡遞減研究，並且計劃最終也對幼兒進行給藥。

In another core modality, the systemic secreted and cell surface therapeutics, we showed the positive Phase I data from additional cohorts of the chikungunya antibody program during our annual R&D Day in September.

在另一種核心模式中，即全身分泌療法和細胞表面療法，我們在 9 月份的年度研發日期間展示了基孔肯雅抗體項目其他隊列的陽性 I 期數據。

Importantly, we demonstrated not only potentially therapeutic levels of a secreted systemic protein, but that a 2-dose regimen with a week between doses was safe and well tolerated and led to the predicted increase in chikungunya antibody productions. This demonstrates our platform's ability for repeat dosing. I'd further note that as a result of rapid systemic clearance, no significant accumulation of our lipid nanoparticle was seen after administration of the second weekly dose.

重要的是，我們不僅證明了分泌的全身蛋白的潛在治療水平，而且兩次劑量之間間隔一周的劑量方案是安全的且耐受性良好，並導致基孔肯雅抗體產量的預期增加。這證明了我們的平台重複給藥的能力。我還要進一步指出，由於快速全身清除，在給予第二週劑量後沒有觀察到我們的脂質納米顆粒的顯著積累。

Moving to Slide 8 and the updates from our pipeline of candidates across the 4 exploratory modalities, and starting with our personalized cancer vaccine, the PCV. Randomized head-to-head trial of PCV with KEYTRUDA versus KEYTRUDA alone in the adjuvant melanoma setting is ongoing. A reminder that our Phase I study continues with patients in the various tumor types who were treated in the monotherapy cohort A and combination cohort B are in follow-up, and the Phase I expansion cohorts of cohort C is enrolling patients. Cohort D in the adjuvant melanoma is also ongoing.

轉到幻燈片 8，以及我們跨 4 種探索模式的候選藥物管道的更新，首先是我們的個性化癌症疫苗 PCV。 PCV 聯合 KEYTRUDA 與單獨 KEYTRUDA 在黑色素瘤輔助治療中的隨機頭對頭試驗正在進行中。提醒您的是，我們的 I 期研究仍在繼續，對接受單一療法隊列 A 和聯合隊列 B 治療的各種腫瘤類型的患者進行隨訪，隊列 C 的 I 期擴展隊列正在招募患者。輔助黑色素瘤的 D 組也在進行中。

For the intratumoral immuno-oncology, I'm happy to report that we have dosed several patients in the ovarian Phase II expansion study. Recall that we initiated this part of the study just last month, and I believe the team's focus on moving this trial forward, along with the support of our clinical investigators has been very productive.

對於腫瘤內免疫腫瘤學，我很高興地報告，我們已經在卵巢 II 期擴展研究中對幾位患者進行了給藥。回想一下，我們上個月剛剛啟動了這部分研究，我相信團隊對推進這項試驗的關注以及我們臨床研究人員的支持非常富有成效。

Our Triplet program in this modality also continues to enroll and dose patients in Phase I. In our systemic intracellular therapeutics modality, study start-up activities have resumed for the PA program following disruptions due to COVID-19. In addition, Nature published a preclinical study on this program.

我們在此模式下的 Triplet 項目還繼續在第一階段招募患者並給予患者劑量。在我們的全身細胞內治療模式中，在因 COVID-19 造成中斷後，PA 項目的研究啟動活動已恢復。此外，《自然》雜誌還發表了該項目的臨床前研究。

For the MMA program, recall that we announced at R&D Day that we would take forward a next-generation development candidate, mRNA-3705, which recently received a rare pediatric disease designation from FDA.

對於 MMA 項目，回想一下，我們在研發日宣布，我們將推進下一代開發候選藥物 mRNA-3705，該藥物最近獲得了 FDA 的罕見兒科疾病指定。

And finally, regarding our partner-led programs, the Phase I KRAS with Merck and the Phase I interleukin 12 and Phase IIa VEGF studies with AstraZeneca are all ongoing.

最後，關於我們合作夥伴主導的項目，與默克的 I 期 KRAS 以及與阿斯利康的 I 期白細胞介素 12 和 IIa VEGF 研究均正在進行中。

So Slide 9 is a snapshot of our development pipeline. And please note that 8 preclinical programs across 3 different modalities that we didn't touch upon during the clinical review, bringing the total number of programs in development currently to 21.

幻燈片 9 是我們開發流程的快照。請注意，我們在臨床審查期間沒有涉及 3 種不同模式的 8 個臨床前項目，使目前正在開發的項目總數達到 21 個。

So let me move into more detail to mRNA-1273, our vaccine against COVID-19. Slide 10 is a broad overview of where we are. mRNA-1273 elicits a robust immune response across PCs and can protect human and nonhuman primates from the virus taking hold in both the nose and the lungs.

那麼，讓我更詳細地介紹一下 mRNA-1273，這是我們針對 COVID-19 的疫苗。幻燈片 10 全面概述了我們的現狀。 mRNA-1273 在 PC 上引發強大的免疫反應，可以保護人類和非人類靈長類動物免受鼻子和肺部病毒的侵害。

In the clinic at the 100-microgram dose, we observed consistently high levels of neutralizing antibody titers across all adult age groups, and these titers were higher than those seen on average in convalescent sera. And the Phase III COVE trial has completed enrollment, meeting our expectations, and I'll give you more details on the demographics in a moment.

在診所使用 100 微克劑量時，我們觀察到所有成人年齡組的中和抗體滴度始終保持高水平，並且這些滴度高於恢復期血清中的平均滴度。第三期 COVE 試驗已經完成註冊，符合我們的預期，我稍後會向您提供有關人口統計數據的更多詳細信息。

Let me briefly review the Phase I results that were published in the New England Journal of Medicine. mRNA-1273 has been generally safe and well tolerated as the Phase I safety data at 100-microgram across the adult age cohorts demonstrate.

讓我簡單回顧一下發表在《新英格蘭醫學雜誌》上的一期研究結果。正如成人年齡組中 100 微克的 I 期安全數據所證明的那樣，mRNA-1273 總體上是安全的且耐受性良好。

As it relates to tolerability, the most common solicited adverse events were headache, fatigue, myalgia, chills and injection site pain, the majority of which were mild to moderate in severity and self-limited.

由於與耐受性相關，最常見的不良事件是頭痛、疲勞、肌痛、寒戰和注射部位疼痛，其中大多數不良事件的嚴重程度為輕度至中度且具有自限性。

Of note, local and systemic reactogenicity were more common and more frequently moderate in severity after the second dose. One severe solicited systemic adverse event occurred after the second dose, and that was fatigue in the above age 71 age cohort, who received the 100-microgram dose.

值得注意的是，第二次給藥後，局部和全身反應原性更常見，且嚴重程度更常見。第二次給藥後發生了一種嚴重的全身不良事件，即接受 100 微克劑量的 71 歲以上人群中的疲勞。

What is important is that these flu-like symptoms are expected, they're transient and generally mild to moderate in nature, and I believe they correlate with the underlying potency to stimulate an immune response in high levels of neutralizing antibodies.

重要的是，這些類似流感的症狀是預料之中的，它們是短暫的，性質通常為輕度至中度，我相信它們與刺激高水平中和抗體的免疫反應的潛在效力相關。

Importantly, there were no vaccine-related serious adverse events in this trial and no patterns of concern for any clinical labs. And while these numbers are still small, we do not see a difference in safety or reactogenicity profile between younger and older adults.

重要的是，該試驗中沒有發生與疫苗相關的嚴重不良事件，也沒有任何臨床實驗室需要關注的模式。雖然這些數字仍然很小，但我們沒有看到年輕人和老年人之間的安全性或反應原性特徵存在差異。

As it relates to the immunogenicity, I would make 3 points regarding the data. First, we see the same level of neutralizing antibodies in younger and older adults. Second, we see these levels consistently in everybody who received the vaccine.

由於它與免疫原性有關，我想就數據提出三點。首先，我們發現年輕人和老年人的中和抗體水平相同。其次，我們在每個接受疫苗的人身上都看到了這些水平的一致性。

And finally, these levels are higher than those seen on average in the blood of people who had been ill with COVID-19 and whom we expect, by and large, to be immune to a second infection.

最後，這些水平高於患有 COVID-19 的人血液中的平均水平，我們預計這些人總體上對第二次感染具有免疫力。

Now if you follow the time line, you see that the high levels of antibodies are achieved quickly upon boost. And I believe the speed and quality of this immune response speaks to the T cell supports and puts us in a good place to have durable protection.

現在，如果您遵循時間線，您會發現在加強後很快就達到了高水平的抗體。我相信這種免疫反應的速度和質量說明了 T 細胞的支持，並使我們處於獲得持久保護的良好位置。

Slide 13 shows an overview of our Phase III COVE study, which is now fully enrolled with 30,000 participants. The full protocol can be found on our website.

幻燈片 13 顯示了我們的 III 期 COVE 研究概述，該研究現已全部入組，共有 30,000 名參與者。完整的協議可以在我們的網站上找到。

A noteworthy point from this slide include the 1:1 randomization between 100-microgram of mRNA in the vaccine arm and placebo. Every participant in the study was expected to be at higher risk than average of infection, that was inclusion criteria #1. And a significant proportion of subjects were stratified as being risk -- at risk of worse outcomes from COVID-19 should they get infected. These are people over 65 years old or those under 65 years old but with chronic conditions that are risk factors for disease.

這張幻燈片中值得注意的一點包括疫苗組和安慰劑組中 100 微克 mRNA 之間的 1:1 隨機化。預計該研究的每位參與者的感染風險均高於平均水平，這是納入標準#1。很大一部分受試者被劃分為風險人群——如果感染了 COVID-19，他們將面臨更糟糕結果的風險。這些人是 65 歲以上或 65 歲以下但患有屬於疾病危險因素的慢性病的人。

So how did we do in terms of demographics? We're very proud of the hard work of our clinical team, our collaborators at NIAID and our clinical trial sites that led to the successful recruitment of a diverse and representative study population, which is similar to the census of our country, with 37% of study participants coming from diverse communities.

那麼我們在人口統計方面做得如何？我們對我們的臨床團隊、NIAID 的合作者以及我們的臨床試驗中心的辛勤工作感到非常自豪，他們成功招募了多樣化且具有代表性的研究人群，這與我國的人口普查類似，有 37%來自不同社區的研究參與者。

And you can see the breakdown on the left side of this slide. We've enrolled 6,000 Hispanic or Latinx participants and 3,000 Black or African-American participants. Age distribution is shown in the middle. And of note, about 2/3 of the trial participants are older than 45 as the gender distribution was close to evenly split, as is seen on the right.

您可以在這張幻燈片的左側看到細分。我們已經招募了 6,000 名西班牙裔或拉丁裔參與者以及 3,000 名黑人或非裔美國人參與者。年齡分佈顯示在中間。值得注意的是，大約 2/3 的試驗參與者年齡超過 45 歲，因為性別分佈接近均勻，如右圖所示。

So what about risk factors for severe COVID-19 disease? The greatest risk factor is age and 1/4 of participants were over the age of 65.

那麼嚴重 COVID-19 疾病的危險因素又如何呢？最大的風險因素是年齡，1/4 的參與者年齡超過 65 歲。

In addition, 17% were younger, but still at risk of severe disease by virtue of comorbid conditions such that 42% of trial participants are in the high-risk strata of having worse outcomes should they get infected.

此外，17% 的人年齡較小，但由於合併症，仍面臨患嚴重疾病的風險，因此 42% 的試驗參與者處於高風險階層，一旦感染，結果會更糟。

There's another way of looking at it, which looks at the breakdown of the chronic conditions that put people at risk shown on the right. These include diabetes at 36%, severe obesity at 25%, significant cardiac disease at 19% and 18% with chronic lung disease.

還有另一種看待它的方式，即觀察使人們處於危險之中的慢性病的分解，如右圖所示。其中包括 36% 的糖尿病患者、25% 的嚴重肥胖患者、19% 的嚴重心髒病患者和 18% 的慢性肺病患者。

I would note that all in all, over 8,000 of the participants in our study are living with these chronic conditions. Now if you do the math, you'll realize that a significant proportion of participants in the COVE study have the independent risk factors of both an older age and comorbid conditions.

我要指出的是，總的來說，我們研究中有超過 8,000 名參與者患有這些慢性病。現在，如果您計算一下，您就會發現 COVE 研究中很大一部分參與者都具有年齡較大和合併症的獨立危險因素。

So Slide 16 sums it up. Our Phase III COVE study is representative of the many diverse populations that make up our nation, and by extension, many parts of the world. And many people could identify with our study and can find themselves in it.

幻燈片 16 對此進行了總結。我們的第三階段 COVE 研究代表了構成我們國家以及世界許多地區的許多不同人群。許多人能夠認同我們的研究，並能在其中找到自己。

As we're anticipating the results of our COVID-19 vaccine study, let me take a few minutes to review the statistical analysis plan on what happens next. As many of you know, we have 2 interim analyses at 53 and 106 events and a final analysis triggered at 151 events.

當我們期待 COVID-19 疫苗研究的結果時，請允許我花幾分鐘時間回顧一下接下來會發生什麼的統計分析計劃。正如你們許多人所知，我們對 53 和 106 個事件進行了 2 次中期分析，並針對 151 個事件觸發了最終分析。

At the first interim analysis, based on the statistical plan, in order to call it a success, we will need to show vaccine efficacy of 74% or greater. From the graph on the left, you can see that there's a 50% probability of meeting that hurdle, assuming a vaccine efficacy rate of 75%. So there's an element of chance here as well.

在第一次中期分析中，根據統計計劃，為了稱其為成功，我們需要顯示疫苗功效達到 74% 或更高。從左圖可以看出，假設疫苗有效率為 75%，那麼達到這一障礙的概率為 50%。所以這裡也有一個機會的因素。

At the second interim analysis, vaccine efficacy of 57% or greater is required to meet the statistical hurdle. And the probability of meeting this is actually 95% if the actual true vaccine efficacy is 75%.

在第二次中期分析中，需要 57% 或更高的疫苗功效才能滿足統計障礙。如果疫苗的真實功效是75%，那麼滿足這一點的概率實際上是95%。

For the final analysis, as per FDA guidelines, at least a 50% efficacy is required. And again, the probability of meeting that primary end point in the final analysis is in the high 90s, assuming that our true vaccine efficacy rate is 75% or higher.

對於最終分析，根據 FDA 指南，至少需要 50% 的療效。再說一次，假設我們的疫苗真實功效為 75% 或更高，那麼最終分析中達到主要終點的概率高達 90 多分。

What we also need to remember is what's not on this graph. All of these assumptions are driven by the imperative to ensure that we have a high degree of confidence. And I'm talking about statistical confidence that once one of these boundary conditions are crossed, not only do we have an initial point estimate about the vaccine efficacy, but we have a 95% confidence interval that the true efficacy, not the point estimate of the sample, exclude 30% or higher than 30%. And I'm sure we'll be coming back to this crucial point in the future.

我們還需要記住的是這張圖表上沒有的內容。所有這些假設都是為了確保我們擁有高度的信心。我說的是統計置信度，一旦跨越這些邊界條件之一，我們不僅有關於疫苗功效的初始點估計，而且我們有 95% 的置信區間，即真實功效，而不是點估計樣本中，排除30%或高於30%。我確信我們將來會回到這個關鍵點。

So on each interim analysis, there are 3 potential outcomes. Either the study meets the statistical hurdle, which is 74% at the first interim and greater than 57% in the second, enable us to trigger the full analysis required to evaluate whether to proceed with the regulatory submission and of course, the trial remains blinded and data continue to accrue at this time; the study may not meet the statistical hurdle and then would continue to the next milestone; or the study is determined to be futile.

因此，每個中期分析都有 3 個潛在結果。要么該研究滿足統計障礙（第一次中期為 74％，第二次中期超過 57％），使我們能夠觸發評估是否繼續向監管機構提交所需的全面分析，當然，試驗仍然是盲法此時數據繼續累積；研究可能無法達到統計障礙，然後將繼續到下一個里程碑；或者研究被確定是徒勞的。

As we have committed to and have been transparent throughout the Phase III clinical program, today, we released the informed consent form of our Phase III study on our website, and we will continue to be transparent. We'll announce the results and the next step once the first interim analysis has occurred.

由於我們一直致力於並在整個 III 期臨床計劃中保持透明，今天，我們在我們的網站上發布了 III 期研究的知情同意書，我們將繼續保持透明。第一次中期分析完成後，我們將宣布結果和下一步行動。

Now the pressure on the results are driven by the fact that from a distribution standpoint, we're ready. We expect mRNA-1273 to be distributed within existing infrastructure. There's nothing new required that hasn't already been used for years with many other vaccines.

現在，結果的壓力來自於這樣一個事實：從分配的角度來看，我們已經準備好了。我們預計 mRNA-1273 將分佈在現有基礎設施內。沒有任何新的要求是多年來未與許多其他疫苗一起使用的。

Specifically, the advantages of mRNA-1273 that allows us to do this include the ability to package and ship boxes in any configuration, housing small or large quantities of vaccine, storage conditions of minus 20 degrees Celsius for 6 months, refrigeration temperatures of 2 to 8 for up to a week and room temperatures conditions for up to 12 hours after thaw.

具體來說，使我們能夠做到這一點的 mRNA-1273 的優勢包括能夠以任何配置包裝和運輸盒子、容納少量或大量疫苗、-20 攝氏度的儲存條件長達 6 個月、冷藏溫度為 2 至8 解凍後最多可保存一周，室溫條件下最多可保存12 小時。

No special handling or dilution is required part of vaccination with mRNA-1273. And by the end of this year, we expect to have approximately 20 million doses ready to ship in the U.S.

mRNA-1273 疫苗接種不需要特殊處理或稀釋。到今年年底，我們預計將有大約 2000 萬劑疫苗準備在美國發貨。

With that, let me turn it over to David to take you through the financials.

接下來，讓我把它交給大衛，讓他帶你了解一下財務狀況。

Okay. Thank you, Tal. Turning to Slide 21 in the deck. We ended Q3 2020 with cash and investments of $3.97 billion compared to $3.07 billion at the end of Q2. The increase is primarily driven by $1.1 billion of customer deposits received in the third quarter for a potential supply of mRNA-1273.

好的。謝謝你，塔爾。轉到幻燈片中的第 21 張幻燈片。截至 2020 年第三季度末，我們的現金和投資為 39.7 億美元，而第二季度末為 30.7 億美元。這一增長主要是由於第三季度收到的 11 億美元客戶存款用於 mRNA-1273 的潛在供應。

Net cash provided by operating activities was $763 million for the 9 months ended September 2020 compared to net cash used of $360 million for the same period in 2019. The reversal from cash used to cash provided by operating activities is driven by total customer deposits for the 9 months ended September 30 of $1.2 billion received for a potential supply of mRNA-1273.

截至2020 年9 月的9 個月，經營活動提供的現金淨額為7.63 億美元，而2019 年同期使用的現金淨額為3.6 億美元。從經營活動使用的現金轉為經營活動提供的現金是由客戶存款總額推動的截至 9 月 30 日的 9 個月內，已收到 12 億美元的 mRNA-1273 潛在供應。

Cash used for purchases of property and equipment was $44 million for the 9 months ended September 2020 compared to $25 million in 2019. Total revenue was $158 million for Q3 2020 compared to $17 million for the same period in 2019. Total revenue was $233 million for the 9 months ended September 2020 compared to $46 million for the same period in 2019. Total revenue increased for both the 3- and 9-month periods in 2020, primarily due to increases in grant revenue from BARDA to accelerate development of mRNA-1273.

截至2020 年9 月的9 個月，用於購買財產和設備的現金為4400 萬美元，而2019 年為2500 萬美元。2020 年第三季度的總收入為1.58 億美元，而2019 年同期為1700萬美元。2020 年第三季度的總收入為2.33 億美元截至2020 年9 月的9 個月，2019 年同期為4600 萬美元。2020 年3 個月和9 個月的總收入均有所增加，主要是由於BARDA 為加速mRNA-1273 開發而增加的撥款收入。

Research and development expenses were $344 million for Q3 2020 compared to $120 million for the same period in 2019. Research and development expenses were $612 million for the 9 months ended September 2020 compared to $378 million for the same period in 2019. The increases for both 3- and 9-month periods in 2020 were mainly due to increased mRNA-1273 clinical development activities and headcount and prelaunch inventory buildup.

2020 年第三季度的研發費用為 3.44 億美元，而 2019 年同期為 1.2 億美元。截至 2020 年 9 月的 9 個月，研發費用為 6.12 億美元，而 2019 年同期為 3.78 億美元。 2020 年3 個月和9 個月期間的增長主要是由於mRNA-1273 臨床開發活動、人員數量和上市前庫存增加的增加。

Overall, in both periods, we saw a significant increase in expenses for the prophylactic vaccines modality as a result of our focus on mRNA-1273.

總體而言，在這兩個時期，由於我們對 mRNA-1273 的關注，我們發現預防性疫苗方式的費用顯著增加。

General and administrative expenses were $49 million for Q3 2020 compared to $28 million for the same period in 2019. Expenses were $109 million for the 9 months ended September 2020 compared to $84 million for the same period in 2019. The increases for both periods were mainly driven by increases in personnel, outside services and set-up costs associated with preparation for commercialization of mRNA-1273 globally.

2020 年第三季度的一般及行政費用為4900 萬美元，而2019 年同期為2800 萬美元。截至2020 年9 月的9 個月費用為1.09 億美元，而2019 年同期為8400 萬美元。這兩個時期的增長主要是由於與 mRNA-1273 全球商業化準備相關的人員、外部服務和設置成本的增加。

Turning to selected cash flow information on Slide 22. On the top half of the page, we present the information from our 10-K and 10-Q filings. And on the bottom part, we provide the quarterly trend and also items to take into consideration when assessing the evolution of this trend, in particular for Q2 and Q3 of this year. Cash provided by operating activities and for purchase of property and equipment was $719 million for the 9-month period ended September 30 and $874 million in the third quarter alone.

轉向幻燈片 22 上選定的現金流量信息。在頁面的上半部分，我們展示了 10-K 和 10-Q 文件中的信息。在底部，我們提供了季度趨勢以及評估這一趨勢演變時需要考慮的事項，特別是今年第二季度和第三季度。截至 9 月 30 日的 9 個月期間，經營活動以及購買財產和設備提供的現金為 7.19 億美元，僅第三季度就為 8.74 億美元。

Excluding deposits received for potential supply of mRNA-1273 and the Vertex upfront payment, cash used in operating activities and for purchase of property and equipment was $296 million in the third quarter. This compares to $118 million in the second quarter of this year excluding customer deposits received in Q2. The increased cash used of around $200 million in Q3 compared to previous quarters, is consistent with our expectation, as we are making substantial investments in manufacturing and potential global commercialization activities for mRNA-1273 COVID vaccine candidate.

不包括因潛在供應 mRNA-1273 而收到的存款和 Vertex 預付款，第三季度用於經營活動以及購買財產和設備的現金為 2.96 億美元。相比之下，今年第二季度的收入為 1.18 億美元，不包括第二季度收到的客戶存款。與前幾個季度相比，第三季度使用的現金增加了約2 億美元，這與我們的預期一致，因為我們正在對mRNA-1273 COVID 候選疫苗的製造和潛在的全球商業化活動進行大量投資。

Let me now give you an overview about where we stand with regard to commercialization activities. Please turn to Slide 23. On Slide 23, you see listed supply agreements that we have announced publicly today. As a reminder, these include the agreement with the U.S. government for 100 million doses and options for an additional 400 million doses. We just announced a deal with Japan for 50 million doses. Canada has confirmed 20 million doses with an option for an additional 36 million. We have also signed agreements with Switzerland, Israel and Qatar, and there are several other countries that have signed agreements that have not been publicly disclosed. We are thankful for the trust the governments around the world have placed in us to deliver a vaccine for their countries.

現在讓我向您概述一下我們在商業化活動方面的立場。請參閱幻燈片 23。在幻燈片 23 上，您可以看到我們今天公開宣布的列出的供應協議。提醒一下，其中包括與美國政府簽署的 1 億劑疫苗協議以及額外 4 億劑疫苗的選擇。我們剛剛宣布與日本達成 5000 萬劑疫苗的協議。加拿大已確認接種 2000 萬劑疫苗，並可選擇額外接種 3600 萬劑。我們還與瑞士、以色列和卡塔爾簽署了協議，還有其他幾個國家簽署了尚未公開披露的協議。我們感謝世界各國政府對我們為他們的國家提供疫苗的信任。

All of these agreements contain provisions for deposits and have contributed to our 3Q '20 deferred revenue value of $1.2 billion, including $600 million from the U.S. government. We continue to work with the European Union, where we are in advanced discussions to supply 80 million to 160 million doses. Negotiations with other countries are also ongoing, including with COVAX on the tiered pricing proposal.

所有這些協議都包含存款條款，並為我們 20 年第三季度的遞延收入貢獻了 12 億美元，其中包括來自美國政府的 6 億美元。我們繼續與歐盟合作，正在進行深入討論，以供應 8000 萬至 1.6 億劑疫苗。與其他國家的談判也在進行中，包括與 COVAX 就分級定價提案進行的談判。

As a reminder, pricing for agreements with smaller volume were executed at $32 per dose or $64 for 2 vaccination course to $37 per dose or $74 per course. We remain on track to fulfill these contracts with anticipated supply between 500 million and 1 billion doses in 2021.

提醒一下，小批量協議的定價為每劑 32 美元或 2 個疫苗接種療程 64 美元，到每劑 37 美元或每療程 74 美元。我們仍有望履行這些合同，預計 2021 年供應量將在 5 億至 10 億劑之間。

Turning now to our 2020 financial update on Slide 24. On an overall basis, we now expect net cash provided by operating activities and purchases of property and equipment in 2020 in the range of positive $0.1 billion to $0.3 billion. The change compared to our update in Q2 is primarily driven by the increase in customer deposits for the potential supply of mRNA-1273 as well as upfront payments for recently announced collaboration agreements with Vertex and Chiesi.

現在轉向幻燈片 24 上的 2020 年財務更新。總體而言，我們現在預計 2020 年經營活動以及購買財產和設備所提供的淨現金將在 1 億至 3 億美元之間。與我們第二季度的更新相比，這一變化主要是由於 mRNA-1273 潛在供應的客戶存款增加以及最近宣布的與 Vertex 和 Chiesi 合作協議的預付款所致。

Let me provide you more color on the individual components of our financial outlook. With regard to the ongoing investment in our portfolio, excluding our COVID vaccine candidate and associated activities, we remain on track to our prior outlook. We expect net cash used in operating activities and purchases of property and equipment to be approximately $0.4 billion in 2020, reflecting an improvement of $0.1 billion from prior outlook. This change is entirely driven by business development activities and related upfront payments as investment levels remain consistent with prior outlooks.

讓我為您提供有關我們財務前景各個組成部分的更多信息。關於我們投資組合的持續投資（不包括我們的新冠疫苗候選藥物和相關活動），我們仍保持先前的展望。我們預計 2020 年用於經營活動以及購買財產和設備的淨現金約為 4 億美元，較之前的預期提高 1 億美元。這一變化完全是由業務開發活動和相關預付款驅動的，因為投資水平與之前的前景保持一致。

Turning now to the financial impacts of our rapidly advancing mRNA-1273 COVID vaccine. 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 24.

現在談談我們快速發展的 mRNA-1273 COVID 疫苗的財務影響。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 24 中單獨顯示。

Next, looking at the COVID vaccine-related net investments, primarily for manufacturing a product to be commercialized in the U.S. and internationally. We expect the cash impact of COVID-related investments to be $0.5 billion to $0.65 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.

接下來，看看與新冠疫苗相關的淨投資，主要用於製造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達到 5 億至 6.5 億美元。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。

Additionally, this investment includes initial commercial infrastructure build-out and costs related to our supply agreements. The subtotal of net cash used in operating activities for all of Moderna's business is currently expected to total $0.9 billion to $1.05 billion before consideration of customer deposits. Including the customer deposits received by the end of September, which sum to $1.2 billion, we expect the total net contribution from cash provided by operating activities and used for purchase of property and equipment of positive $0.1 billion to $0.3 billion. We expect this number to increase as we continue to receive further deposits.

此外，這項投資包括初始商業基礎設施建設以及與我們的供應協議相關的成本。在考慮客戶存款之前，Moderna 所有業務經營活動中使用的淨現金小計目前預計總計 9 億至 10.5 億美元。包括截至 9 月底收到的 12 億美元客戶存款，我們預計經營活動提供的現金以及用於購買財產和設備的現金淨貢獻總額為正 1 億至 3 億美元。隨著我們繼續收到更多存款，我們預計這一數字將會增加。

Turning now to Slide 25. As we progress towards approval and commercialization of mRNA-1273, there's heightened interest in several areas of accounting that will increasingly impact our reported results as we move forward. Slide 25 highlights some key areas which will change with an approval event, for example, an Emergency Use Authorization in the United States.

現在轉向幻燈片25。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 25 重點介紹了一些將隨批准事件而變化的關鍵領域，例如美國的緊急使用授權。

Costs associated with prelaunch inventory are currently fully expensed to R&D expense in the period incurred. This includes costs for acquired raw materials as well as production costs. After an approval event, we will capitalize our inventory to the extent that the commercialization is determined to be probable, and we expect future economic benefits from sales to be realizable. In the third quarter of 2020, we expensed prelaunch inventory of $52 million, largely raw materials.

與上市前庫存相關的成本目前已全部計入發生期間的研發費用。這包括採購原材料的成本以及生產成本。在獲得批准後，我們​​將在確定可能進行商業化的情況下將我們的庫存資本化，並且我們預計未來可以從銷售中獲得經濟利益。 2020 年第三季度，我們支出了 5200 萬美元的上市前庫存，其中大部分是原材料。

The costs associated with purchases of property and equipment or leased assets related to our mRNA-1273 program are evaluated for all assets with alternative use will be capitalized. Example of these assets include IT and general production infrastructure.

與購買與我們的 mRNA-1273 項目相關的財產和設備或租賃資產相關的成本將被評估為所有具有替代用途的資產將被資本化。這些資產的示例包括 IT 和一般生產基礎設施。

Assets acquired to meet the current production needs of mRNA-1273 and before product approval will be expensed immediately as costs are incurred. This reflects the fact that Moderna does not yet have other platform products approved or commercialized after a regulatory approval event. When PP&E and leased assets are no longer required to be assessed for alternative use, such assets will be capitalized. In Q3, we recorded $10 million of PP&E as expense.

為滿足 mRNA-1273 目前的生產需求以及在產品批准之前購買的資產將在發生成本時立即費用化。這反映了 Moderna 在獲得監管批准後尚未批准或商業化其他平台產品的事實。當不動產、廠房和租賃資產不再需要評估其替代用途時，此類資產將被資本化。第三季度，我們將 1000 萬美元的 PP&E 記錄為費用。

On product sales, customer deposits for a potential supply of mRNA-1273 are recorded as deferred revenue and will be recognized as revenue when control of approved product has been transferred to the customer and customer acceptance has occurred.

在產品銷售方面，潛在供應 mRNA-1273 的客戶存款記錄為遞延收入，並將在批准產品的控制權已轉移給客戶且客戶接受後確認為收入。

In Q3, we recorded $1.1 billion of incremental deferred revenues associated with potential future supply of mRNA-1273. No product revenue was recognized in the quarter. 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.

在第三季度，我們記錄了與 mRNA-1273 未來潛在供應相關的 11 億美元增量遞延收入。本季度沒有確認產品收入。 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。

As of 12/31/2019, we had $982 million of federal and state accumulated net operating loss carryforwards and $471 million of net deferred tax assets, which were fully reserved as we concluded that realization of our net deferred tax assets does not yet, more likely than not, to be realized. After a regulatory approval event and as we expect to utilize the NOLs, we will reverse and release the valuation allowance or portion of the allowance, which will result in a tax benefit in our income statement.

截至2019 年12 月31 日，我們有9.82 億美元的聯邦和州累計淨營業虧損結轉和4.71 億美元的淨遞延稅資產，這些資產已全部保留，因為我們得出的結論是，我們的淨遞延稅資產尚未實現，更多很可能會被實現。在監管部門批准後，由於我們預計將使用 NOL，我們將沖銷並釋放估值津貼或部分津貼，這將在我們的損益表中帶來稅收優惠。

This concludes the financial update, and I turn now the call back to Stéphane.

財務更新到此結束，我現在將電話轉回給 Stéphane。

Thank you, Tal and David. In closing, I would like to step back for a few minutes. Across the world, we are all rightly so very focused on the pandemic, the race against the virus, both with therapeutics and vaccines. The Moderna team has been incredibly focused in 2020 on getting mRNA-1273 to the market in record time.

謝謝你們，塔爾和大衛。最後，我想退後幾分鐘。在世界各地，我們都非常關注這一流行病，通過治療方法和疫苗與病毒進行競賽。 Moderna 團隊在 2020 年非常專注於以創紀錄的時間將 mRNA-1273 推向市場。

But an important part of my role is to look into the future, not only in the next few weeks, for the next few years. And to look at the big picture, not only to look at Moderna. I believe Moderna entered 2020 in a strong position, with a strong cash position of approximately $1.3 billion. With a diverse clinical portfolio of vaccines and therapeutics across 6 different modalities, we have always focused on a portfolio approach to reduce technology risk. We have 20 development candidates. We have sustained over 9 years since inception, large investments in platform science, mRNA and LNP formulation. We had established a very broad and strong IP portfolio. We have sustained large investments in process development. We own a fully integrated plant that allowed us to go from raw materials to filled vials for all of our clinical needs at scale and with unprecedented speed.

但我角色的一個重要部分是展望未來，不僅是未來幾週，還有未來幾年。並著眼於大局，而不僅僅是著眼於 Moderna。我相信 Moderna 在進入 2020 年時處於強勢地位，擁有約 13 億美元的強勁現金狀況。憑藉 6 種不同模式的多樣化疫苗和治療藥物臨床組合，我們始終專注於降低技術風險的組合方法。我們有 20 名開發候選人。自成立以來，我們在平台科學、mRNA 和 LNP 配方方面持續進行了 9 年多的大量投資。我們已經建立了非常廣泛和強大的知識產權組合。我們在工藝開發方面持續進行了大量投資。我們擁有一個完全一體化的工廠，使我們能夠以前所未有的速度從原材料到灌裝小瓶，滿足我們所有的臨床需求。

As I look at the end of 2021, 14 months from now, I believe that if we launch mRNA-1273, we will exit the COVID pandemic crisis in a unique position. We should have a strong cash balance at the end of 2021. It will be made of $4 billion at hand as of September 30, 2020 plus the cash flow that we should generate in fiscal year 2021. The U.S. government has taken a very thoughtful approach with Operation Warp Speed, or OWS. They decided to support 3 vaccine technologies, including mRNA, to diversify risk to ensure we got several vaccines to a finish line for the U.S. citizens. They decided to back only 2 companies per technology. Moderna was 1 of the 2 companies that the U.S. government ordered 100 million doses from. That is a very important market access. We are grateful for the trust of the U.S. government have placed in us, our development process and our technology, and we are very thankful for the help.

展望 2021 年底，即 14 個月後，我相信，如果我們推出 mRNA-1273，我們將以獨特的方式擺脫新冠病毒大流行危機。到2021 年底，我們應該擁有強勁的現金餘額。截至2020 年9 月30 日，我們手頭的現金餘額將達到40 億美元，加上我們在2021 財年應該產生的現金流。美國政府採取了非常周到的方法與曲速行動（OWS）。他們決定支持 3 種疫苗技術，包括 mRNA，以分散風險，確保我們為美國公民提供多種疫苗。他們決定每種技術只支持 2 家公司。 Moderna 是美國政府向其訂購 1 億劑疫苗的兩家公司之一。這是非常重要的市場准入。我們感謝美國政府對我們、我們的開發過程和我們的技術的信任，我們非常感謝他們的幫助。

Moderna retains worldwide rights to develop and commercialize mRNA-1273. Without a corporate partner, Moderna will realize all the profits from our COVID-19 vaccine. We intend to reinvest the returns from the sales of a vaccine into our pipeline development and hope to bring more medicines to the market. I believe that the long-term strategic implications are large. We should have a unique cash position at the end of 2021.

Moderna 保留在全球範圍內開發和商業化 mRNA-1273 的權利。如果沒有企業合作夥伴，Moderna 將實現我們的 COVID-19 疫苗的所有利潤。我們打算將疫苗銷售的回報再投資到我們的管道開發中，並希望將更多的藥物推向市場。我相信長期戰略意義是巨大的。到 2021 年底，我們應該擁有獨特的現金頭寸。

Moderna has been built to scale because mRNA is an information molecule. We invested relentlessly in science at scale that no other company could have thought: in robotics, in digital, in process development, in a large manufacturing plant. We have always been limited in the last 5 years with cash. I believe that this is about to change in a very material way during fiscal year 2021. The approval of mRNA-1273 for commercialization would provide a unique derisking of the entire Moderna vaccine platform. We use the same chemistry to make each mRNA vaccine, with the same manufacturing process to make the MRNA. We have the same chemistry for lipid, the same manufacturing process to formulate the mRNA in our lipid. Think about what this team could do over the next 5 to 10 years, starting from a growing cash balance north of $4 billion and the knowledge that our technology leads to approved vaccine.

Moderna 是按比例構建的，因為 mRNA 是一種信息分子。我們對科學的持續投資規模是其他公司無法想像的：機器人、數字化、工藝開發、大型製造工廠。過去5年我們的現金一直很有限。我相信這種情況將在 2021 財年發生重大改變。mRNA-1273 商業化的批准將為整個 Moderna 疫苗平台提供獨特的風險降低方案。我們使用相同的化學物質來製造每種 mRNA 疫苗，並採用相同的製造工藝來製造 mRNA。我們的脂質具有相同的化學成分，並且採用相同的製造工藝來配製脂質中的 mRNA。考慮一下這個團隊在未來 5 到 10 年內可以做些什麼，從不斷增長的現金餘額超過 40 億美元以及我們的技術導致疫苗獲得批准的知識開始。

I believe 2021 will be the most important inflection year in Moderna history. Early on, we recognized that mRNA could be an entire new class of medicines. We always said since day 1 that it made no sense that this would be a one product company. It will be 0 if we failed to make safe and efficacious product, or it will be a new class of medicine changing medicine forever.

我相信2021年將是Moderna歷史上最重要的轉折年。很早就，我們認識到 mRNA 可能是一類全新的藥物。從第一天起我們就一直說，這將是一家單一產品公司是沒有意義的。如果我們不能做出安全有效的產品，那麼它就是0，否則它將永遠改變醫學的一類新藥。

Our mission to deliver on the promise of mRNA science to create a new generation of transformative medicine for patients is one we strive for every single day.

我們的使命是兌現 mRNA 科學的承諾，為患者創造新一代變革性藥物，這是我們每天都在努力實現的使命。

In 2020, we didn't do it alone. We had many partners, the NIH, BARDA, Lonza, ROVI, Catalent, PPD, the clinicians that execute our clinical trials and our team. I'm very thankful for the clinical trial participants for their trust and the participation in our trials. With that, we will now be happy to take your questions. Thank you. Operator?

2020年，我們並不是孤軍奮戰。我們有很多合作夥伴，包括 NIH、BARDA、Lonza、ROVI、Catalent、PPD、執行我們臨床試驗的臨床醫生和我們的團隊。我非常感謝臨床試驗參與者的信任和參與我們的試驗。這樣，我們現在很樂意回答您的問題。謝謝。操作員？

(Operator Instructions) And our first question comes from the line of Salveen Richter with Goldman Sachs.

（操作員說明）我們的第一個問題來自高盛的薩爾文·里克特（Salveen Richter）。

COVID-19 vaccine. So just given the commentary from the recent FDA Ad Com on COVID-19, just would like your thoughts here about how you intend to unblind potentially on the first interim or post the full 3 looks in the study. And then secondly, just time lines around vaccine EUA just given some of the commentary. And I think Dr. Fauci talking about a January green light for vaccines.

嚴重特殊傳染性肺炎疫苗.因此，鑑於最近 FDA Ad Com 對 COVID-19 的評論，我想了解您的想法，了解您打算如何在第一次臨時揭盲或在研究中發布完整的 3 個外觀。其次，關於疫苗 EUA 的時間表剛剛給出了一些評論。我認為福奇博士正在談論一月份為疫苗開綠燈。

This is Tal. Let me try and take that. I think the bottom line here is that we feel, I think, an obligation to the participants of the COVE study, especially those for whom an EUA will be appropriate that there's a way for them to ultimately benefit from what they themselves have contributed to. Now of course, I think we all listened intently to Vertex last week. There's a balance to be had here.

這是塔爾。讓我嘗試一下。我認為這裡的底線是，我認為，我們對 COVE 研究的參與者有義務，特別是那些適合 EUA 的參與者，因為他們有辦法最終從他們自己所做的貢獻中受益。當然，我想上週我們都專心聆聽了 Vertex 的演講。這裡需要保持平衡。

The way I think this is going to happen at the end of the day, unfortunately, the cases are accruing. We're in a period of increasing transmission. And so I expect that there will be some time between knowing that the bar has been crossed for efficacy doing the analysis and discussing with FDA. And part of that conversation is finding the right balance of how long do you continue to collect blinded data, and what is the type of data that one can collect post blinding but still on trial. I mean if you do a math, if you're looking for very, very safety events, for example, then an unblinded study actually could give you power to detect that even more than a blinded trial.

我認為這最終會發生，不幸的是，案件正在增加。我們正處於傳播增加的時期。因此，我預計在進行分析和與 FDA 討論之間會需要一段時間才能知道功效已被突破。對話的一部分是找到適當的平衡點，即繼續收集盲法數據多長時間，以及盲法後可以收集但仍在試驗中的數據類型是什麼。我的意思是，如果你做數學計算，如果你正在尋找非常非常安全的事件，那麼非盲研究實際上可以讓你更有能力發現這一點，甚至比盲試驗更有效。

So a lot of these elements, I think, are going to go into the conversation that we're having with FDA. And I'm confident that together with them, we will find the right balance as to how to operationalize this.

因此，我認為，我們與 FDA 的對話將涉及其中很多內容。我相信，與他們一起，我們將在如何實施這一問題上找到適當的平衡。

As it relates to the timing, I think we're on track to have the first interim in November. I think I expect, unfortunately, that we're going to be on track for additional cases occurring in December and beyond. And so the totality of data in the coming months, I think, will cross that threshold. I anticipate for efficacy. And the rest will be a dialogue with FDA and other regulatory agencies on the right process by which to ensure we demonstrate the safety and efficacy and ultimately, make the vaccine available.

就時間安排而言，我認為我們有望在 11 月舉行第一次臨時會議。不幸的是，我想我預計我們將在 12 月及以後出現更多病例。因此，我認為未來幾個月的數據總量將突破這一閾值。我期待功效。剩下的工作將是與 FDA 和其他監管機構就正確的流程進行對話，以確保我們證明疫苗的安全性和有效性，並最終使疫苗可用。

Our next question comes from the line of Matthew Harrison with Morgan Stanley.

我們的下一個問題來自摩根士丹利的馬修哈里森。

I guess 2 related questions from me. Tal, can you comment at all about the attack rate that you're seeing in the study? I think given the Pfizer comments earlier this week, there's a lot of confusion among investors about whether the attack rate in these studies mirrors what we're seeing in the general population or if it's somehow lower than what we're seeing in the general population.

我想我有兩個相關的問題。 Tal，您能對您在研究中看到的攻擊率發表一下評論嗎？我認為，考慮到輝瑞本週早些時候的評論，投資者對這些研究中的攻擊率是否反映了我們在普通人群中看到的情況，或者是否低於我們在普通人群中看到的情況存在很多困惑。 。

And then a related question, something else that I think has come up a lot is this concern about functional unblinding potentially due to people recognizing some of the features of the boost, and that may be leading towards certain people taking on different behavior which may lead to this lower event rate. So I was wondering if you could talk about -- if you have a concern about functional unblinding, and especially related to the fact that you obviously have the placebo data from the Phase II study so you have a much better idea of placebo-adjusted tolerability versus what we've seen from an open-label study.

然後是一個相關的問題，我認為已經出現了很多問題，那就是對功能揭盲的擔憂，這可能是由於人們認識到了增強的某些特徵，這可能會導致某些人採取不同的行為，這可能會導致到這個較低的事件發生率。所以我想知道你是否可以談談——如果你對功能揭盲有擔憂，特別是與你顯然擁有來自第二階段研究的安慰劑數據這一事實有關，這樣你就可以更好地了解安慰劑調整的耐受性與我們從開放標籤研究中看到的結果相比。

Thanks, Matthew. Let me try and give you a sense of how I see the data. First of all, my sense from the emerging data is that the attack rates of our trial participants do mirror what we see in those zip codes where the subjects are coming from. It's not a surprise because if you look at the demographics of what we've been able to achieve in the COVE study, having so many people of minorities, older with comorbid conditions, so it's on par with expectations. I think, writ large.

謝謝，馬修。讓我嘗試讓您了解一下我如何看待這些數據。首先，我從新出現的數據中感覺到，我們的試驗參與者的攻擊率確實反映了我們在受試者來自的郵政編碼中看到的情況。這並不奇怪，因為如果你看看我們在 COVE 研究中取得的人口統計數據，就會發現有這麼多少數族裔、老年人患有共病，所以它與預期相符。我認為，寫得大一點。

And unfortunately, with the current attack rates not slowing down the math that we're doing, it's this paradox of more attack rates out there worse off for our subjects, unfortunately, but the data will get there. So that's my sense. Now there is a balance to be had, which I think is -- I've tried to address in the first question that not just us, but everybody in the field is struggling with, which is the accumulation of data versus the eventual unblinding of participants and how does that all play into regulatory expectations. And I think we'll continue to have this dialogue in the coming weeks.

不幸的是，由於當前的攻擊率並沒有減慢我們正在進行的數學計算，不幸的是，更多的攻擊率對我們的受試者來說更加糟糕，這是一個悖論，但數據將會到達那裡。這就是我的感覺。現在需要取得一個平衡，我認為是——我在第一個問題中試圖解決這個問題，不僅是我們，而且該領域的每個人都在努力解決這個問題，即數據的積累與最終揭盲參與者以及這一切如何影響監管期望。我認為我們將在未來幾週內繼續進行這種對話。

Your -- the concern you raised about functional unblinding, yes, I show that. I think we all do, to a certain degree. We chose a dose that we believe is optimal in the sense that people may get some transient flu-like symptoms, but it's worth it for the opportunity to prevent this disease. I don't think this leads to lower event rates per se. I think my biggest concern is that if anything, it would bias us against vaccine efficacy, right? If people behave because they think they got something and that modifies their behavior then and if anything, you would expect that the behaviors would be such that the placebo recipients would be less at risk of getting infected and the vaccine recipients would be more at risk of getting infected.

你對功能性揭盲提出的擔憂，是的，我表明了這一點。我想我們都在某種程度上這樣做。我們選擇了我們認為最佳的劑量，因為人們可能會出現一些短暫的流感樣症狀，但為了有機會預防這種疾病，這是值得的。我不認為這本身會導致事件發生率降低。我認為我最擔心的是，如果有的話，它會讓我們對疫苗功效產生偏見，對嗎？ If people behave because they think they got something and that modifies their behavior then and if anything, you would expect that the behaviors would be such that the placebo recipients would be less at risk of getting infected and the vaccine recipients would be more at risk of受到感染.

So at least from a statistical and robustness of the data, it shouldn't have any adverse effect. If anything, it should hurt us. But I don't expect this ultimately to be significantly changing the event rates. And if I look at the macro picture, as I've said, I think we're going to be on track, unfortunately, for where we anticipate being.

因此，至少從數據的統計和穩健性來看，它不應該產生任何不利影響。如果有的話，它應該傷害我們。但我並不認為這最終會顯著改變事件發生率。如果我從宏觀角度來看，正如我所說，不幸的是，我認為我們將步入預期的軌道。

And our next question comes from the line of Ted Tenthoff with Piper Sandler.

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

Thank you for all of your hard work in bringing -1273 forward. Amazing to see the company turning cash flow positive, huge milestone. I wanted to get a sense for cost of vaccine at the price -- or at the quantities that you're talking about for next year with Lonza.

感謝您為推動 -1273 所做的辛勤工作。令人驚訝的是，公司的現金流轉為正數，這是一個巨大的里程碑。我想通過價格或您與龍沙談論的明年的數量來了解疫苗的成本。

Ted, it's Stéphane. As we've said in the past, we are not disclosing cost of goods for obvious competitive reasons. So I won't be able to answer that question.

特德，我是史蒂芬。正如我們過去所說，出於明顯的競爭原因，我們不會披露商品成本。所以我無法回答這個問題。

And our next question comes from the line of Michael Yee.

我們的下一個問題來自 Michael Yee。

What do you think is going on with the event rates? I know that you said you actually believe you're on time, so maybe it's a question more in part based on the competitor and related to that. Do you actually know your actual event rates? And therefore, you do feel every day that you're seeing the numbers and feel very confident about November. Your competitor missed that time line. So I think everybody is nervous about that. So maybe just make a comment about what you think is going on in general.

您認為事件發生率發生了什麼變化？我知道您說過您確實相信自己準時，所以也許這個問題更多地基於競爭對手並與之相關。您真的知道實際的事件發生率嗎？因此，你確實每天都感覺自己看到了這些數字，並對 11 月感到非常有信心。你的競爭對手錯過了那個時間線。所以我認為每個人都對此感到緊張。因此，也許只是對您認為總體上正在發生的事情發表評論。

And then secondly, because if being on is actually a pretty high interim and I think you've actually commented on that. Maybe just make a comment about if we don't hit that, what that will mean for folks. And I think it has to do mostly with the alpha spend, so that's why I'm not too concerned. But maybe just make a comment about that as well.

其次，因為如果上線實際上是一個相當高的過渡期，我認為你實際上已經對此發表了評論。也許只是評論一下如果我們不實現這一點，這對人們意味著什麼。我認為這主要與阿爾法支出有關，所以這就是為什麼我不太擔心。但也許也只是對此發表評論。

Thank you. Yes, this is Tal. Look, I can't comment about our competitors. I don't know their data, so I'll leave that to them. I can repeat what I said about our sense. We do, of course, see the data coming in. There's a small team at Moderna that's aware of the cases that's following up. That number is, of course, being kept confidential to minimize speculation here. But I can tell you that overall, it -- since we are following the zip codes and the counties from which these participants come, we have pretty sophisticated models of what to expect, and I think we're on track for those expectations. So I think we should be on track for that first interim sometime in November, as we have articulated.

謝謝。是的，這是塔爾。聽著，我無法評論我們的競爭對手。我不知道他們的數據，所以我會把這個留給他們。我可以重複我所說的關於我們的感覺。當然，我們確實看到了傳入的數據。Moderna 有一個小團隊了解正在跟進的案例。當然，這個數字是保密的，以盡量減少猜測。但我可以告訴你，總的來說，由於我們正在跟踪這些參與者來自的郵政編碼和縣，因此我們對預期結果有相當複雜的模型，而且我認為我們正在實現這些預期。因此，我認為我們應該在 11 月的某個時間進行第一次臨時過渡，正如我們所闡明的那樣。

You raised a valid point about the interim, and thank you for asking that. Hitting that interim is going to be a function of what the actual vaccine efficacy is and an element of luck on the distribution of the first batch of data you see. Not hitting it doesn't mean the vaccine doesn't work. And in fact, it doesn't even mean that the vaccine has a less than 75% efficacy. We could easily not hit it and yet come back on the second interim and demonstrate an 80% or 85% efficacy. That's kind of the chance of how the stats work.

您提出了有關過渡時期的一個有效觀點，感謝您提出這個問題。達到這個過渡期將取決於實際疫苗功效的函數，以及您看到的第一批數據分佈的運氣因素。沒有擊中並不意味著疫苗不起作用。事實上，這甚至並不意味著疫苗的功效低於75%。我們很容易沒有達到目標，但在第二次中期恢復並表現出 80% 或 85% 的功效。這就是統計數據如何運作的機會。

I think the alpha spend, et cetera, you're correct, this is a conservative design. And maybe it's an opportunity to dispel a notion. The fact that we crossed the boundary at an interim doesn't mean it's less powerful than a final from a pure statistical standpoint. Once you cross that boundary, you have the same statistical conviction that you would have had on the final.

我認為阿爾法支出等等，你是對的，這是一個保守的設計。也許這是一個消除觀念的機會。事實上，從純粹的統計角度來看，我們在中期跨越了界限並不意味著它不如決賽那麼強大。一旦你跨越了這個界限，你就會擁有與決賽時相同的統計信念。

Now I think the way I think about the data here is irrespective of the point at which we cross the boundary, the trial will continue blinded for a period of time. Data will continue to accrue. And as long as the trial continues blinded, we will get better and better with more and more data to increase the level of certainty we have on all the end points of the trial. So in that regard for me, this first crossing on the interim is just the basis that allows us to go and have confidence to start doing analyses and proceed down the path of regulatory interaction so that we ensure that ultimately, access is not delayed to people when there's such a high need out there in our communities.

現在我認為我對這里數據的看法是，無論我們在哪一點跨越邊界，試驗都會在一段時間內繼續進行盲法。數據將繼續積累。只要試驗繼續進行盲法，我們就會通過越來越多的數據變得越來越好，以提高我們對試驗所有終點的確定性水平。因此，在這方面，對我來說，臨時的第一次跨越只是一個基礎，使我們能夠有信心開始進行分析並沿著監管互動的道路前進，以便我們確保最終不會延遲人們的訪問當我們的社區有如此高的需求時。

And our next question comes from the line of Gena Wang with Barclays.

我們的下一個問題來自巴克萊銀行的 Gena Wang。

Do you also see safety in the blinded format? If so, how is that compared to the Phase I profile? And then 2 questions regarding the interim analysis. So if first interim -- if you missed the first interim, is this due 4 to 8 weeks to hit the second interim? And then for the first interim, what is the futility bundled with?

您是否也看到盲法的安全性？如果是這樣，與第一階段的情況相比如何？然後是關於中期分析的 2 個問題。那麼，如果第一次中期 - 如果您錯過了第一次中期，是否需要 4 到 8 週才能進行第二次中期？那麼在第一個過渡時期，徒勞的事情又是什麼呢？

Let me take that. The safety, yes, we see the totality in a blinded fashion. I would remind you that the independent Data Safety Monitoring Board that's been appointed by the NIH and sees not just our trial, but also the other U.S. -- OWS-sponsored trials in parallel sees both the blinded and the unblinded data. Writ large, I can tell you that, so far, we're not seeing anything unexpected so the trial continues. And in that regard, I don't expect surprises when we eventually unblind.

讓我來吧。安全性，是的，我們以盲目的方式看到了整體。我想提醒您的是，由 NIH 任命的獨立數據安全監測委員會不僅負責我們的試驗，還負責其他由美國 OWS 贊助的並行試驗，同時查看盲態和非盲態數據。大體來說，我可以告訴你，到目前為止，我們沒有看到任何意外情況，因此審判仍在繼續。在這方面，當我們最終揭開盲點時，我預計不會出現意外。

Your second question around the timing is, I think it's a matter of weeks between the first and the second interim, not months. Now I can't be more precise because, obviously, it's a function of the future transmission rates in areas, and I hope that they go down. But for now, just several weeks, not longer.

關於時間安排的第二個問題是，我認為第一次和第二次過渡之間只需要幾週的時間，而不是幾個月的時間。現在我不能更精確了，因為顯然，這是各地區未來傳輸速率的函數，我希望它們會下降。但就目前而言，只有幾週，而不是更長。

In terms of futility, I think the boundary is to show that this is going the wrong way. It's specified to the degree that we felt it was appropriate to specify in the protocol. Beyond that, I can say that it's the reason you have a Data Safety Monitoring Board. You've got, on that panel, several statisticians and several experienced clinicians. So it is where I expect them to exercise their judgment and experience, and they're looking at it closely.

就徒勞性而言，我認為界限是表明這是一條錯誤的道路。它的指定程度是我們認為在協議中指定的適當程度。除此之外，我可以說這就是你們設立數據安全監控委員會的原因。該小組中有幾位統計學家和幾位經驗豐富的臨床醫生。因此，我希望他們在這方面運用自己的判斷力和經驗，並且他們正在密切關注。

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。

This is Matthew on for Cory. Just on the COVE trial and in light of subject mix and commentary that event rates are tracking geographically with infections. I'm wondering what your assumptions are for the proportion of patients with SARS-COVID-2 infection that you expect to ultimately go on to become symptomatic.

這是科里的馬修。就 COVE 試驗而言，根據主題組合和評論，事件發生率在地理上與感染進行追踪。我想知道您對預計最終出現症狀的 SARS-COVID-2 感染患者的比例有何假設。

So let me make -- let me answer that in maybe a simplistic form. The tracking is first and foremost of symptomatic cases because we're not routinely swabbing people just to check PCR as people self-identify. The asymptomatic infection rate will be determined based on serology that distinguishes between infection and immunization by later comparing antibodies against nuclear capsid versus spec protein. So we are primarily aware of the symptomatic infections to begin with, and that is the parameter that we're primarily tracking as it relates to the epidemiology. I hope that answered the question.

因此，讓我以一種簡單的形式來回答這個問題。追踪首先是有症狀的病例，因為我們不會定期對人們進行拭子檢測，只是為了在人們自我識別時檢查 PCR。無症狀感染率將根據血清學來確定，血清學通過隨後比較抗核衣殼抗體和規格蛋白抗體來區分感染和免疫。因此，我們首先主要了解有症狀的感染，這是我們主要跟踪的參數，因為它與流行病學相關。我希望這回答了問題。

Yes. I guess maybe just a follow-up. So when you say that rates are tracking the zip codes, what is the data that you're gathering from outside the trial to benchmark it [to the trial].

是的。我想也許只是後續行動。因此，當您說費率正在跟踪郵政編碼時，您從試驗外部收集的用於對其[試驗]進行基準測試的數據是什麼。

The reporting of case rates and infection rates together, it's -- we've got a couple of independent expert panels and teams here that compile the totality of the data that emerges from the various surveillance programs and sophisticated models to create those predictions.

一起報告病例率和感染率，我們這裡有幾個獨立的專家小組和團隊，他們編譯從各種監測計劃和復雜模型中產生的全部數據來創建這些預測。

If you're asking me to describe what's under that hood, it's a complicated black box for me. But I can tell you that the number that it spits out ultimately looks very close to the number that we see on a daily and weekly basis at this stage. And that's what gives me the confidence.

如果你讓我描述一下引擎蓋下的內容，那對我來說這是一個複雜的黑匣子。但我可以告訴你，它最終得出的數字看起來非常接近我們現階段每天和每週看到的數字。這就是給我信心的原因。

Our next question comes from the line of Geoff Meacham with Bank of America.

我們的下一個問題來自美國銀行的傑夫·米查姆 (Geoff Meacham)。

This is Alec on for Geoff. Can you talk a bit more about the tiered pricing proposal with COVAX? What will this look like? And if you can't talk about the agreement specifically, what's the logic of a tiered structure versus just a set price for certain amount of doses seen in the other supply agreements?

這是亞歷克（Alec）替傑夫（Geoff）發言。您能多談談 COVAX 的分級定價方案嗎？這會是什麼樣子？如果您不能具體談論該協議，那麼與其他供應協議中所見的特定劑量的固定價格相比，分層結構的邏輯是什麼？

And on the Japan supply agreement and I suppose, on most of the OUS supply agreements, how do you plan to allocate manufacturing between your plants and Lonza's? And are there any logistical constraints that would limit the vaccine produced in Norwood geographically? And I guess, just lastly, what's being done to ensure consistency of vaccine produced between both your own internal and the external manufacturing sites?

關於日本供應協議，我想，對於大多數 OUS 供應協議，您計劃如何在您的工廠和 Lonza 工廠之間分配製造？是否存在任何物流限制會在地理上限制諾伍德生產的疫苗？我想，最後，正在採取哪些措施來確保您自己的內部和外部生產基地之間生產的疫苗的一致性？

Alec, Stéphane. So it's a lot of questions. If I forget some, let me know. So on COVAX, what we want to do is to make sure that the vaccine is available around the world. As you know, we believe, based on the -- I mean, on the early development data that the vaccine has a chance to be protective across different age range. And we think it's very important. And so we want the vaccine to be available to help as many people as we can.

亞歷克、史蒂芬.所以有很多問題。如果我忘記了一些，請告訴我。因此，在 COVAX 上，我們想做的是確保疫苗在世界各地都能使用。如您所知，我們相信，根據 - 我的意思是，根據早期開發數據，疫苗有機會在不同年齡範圍內發揮保護作用。我們認為這非常重要。因此，我們希望疫苗能夠幫助盡可能多的人。

The tiered pricing is very typical of what Gavi has done in the past. As I'm sure you are aware, COVAX is being run by Gavi and CEPI. And so the idea here is to propose to low-income countries and middle-income countries a price that is lower than the price being paid by developed countries or high-income countries. And so that's basically the idea. And so of course, we're not in a position to disclose those prices today because the discussions are ongoing with COVAX. But what we want to make sure as a company is that we are able to provide vaccines at a lower cost for low-income and middle-income country.

分級定價是全球免疫聯盟過去所做的非常典型的做法。我相信您知道，COVAX 由 Gavi 和 CEPI 運營。因此，這裡的想法是向低收入國家和中等收入國家提出一個低於發達國家或高收入國家所支付價格的價格。這基本上就是這個想法。當然，我們今天無法透露這些價格，因為正在與 COVAX 進行討論。但作為一家公司，我們想要確保的是，我們能夠以較低的成本為低收入和中等收入國家提供疫苗。

In terms of quality across the board, I would say it's very typical of what is done in any biopharmaceutical company when you have several sites in terms of a quality organization, technology transfer, validation and so on to ensure that a product that is made at Lonza, in this product, Lonza, in New Hampshire or at Moderna in Massachusetts is of the same quality and the same spec.

就全面質量而言，我想說，這是任何生物製藥公司的典型做法，當您在質量組織、技術轉讓、驗證等方面擁有多個站點時，以確保在Lonza，在該產品中，新罕布什爾州的Lonza 或馬薩諸塞州的Moderna 具有相同的質量和相同的規格。

And then in terms of allocation, so as we said in the past, we set up the supply chain, the U.S. supply chain, Moderna in Massachusetts and Lonza in New Hampshire. To focus initially on the U.S., we set up the supply chain in Lonza this to be initially focused outside the U.S. as -- and I think this is going to really hold for the first, I would say, 2 quarters after launch. After such a time, we are going to set up the supply chain in terms of regulatory filing, so that products can be moved around.

然後在分配方面，所以就像我們過去說的，我們建立供應鏈，美國供應鏈，馬薩諸塞州的Moderna和新罕布什爾州的Lonza。為了最初專注於美國，我們在 Lonza 建立了供應鏈，最初將重點放在美國以外的地區，我認為這將在發布後的第一個，我想說的兩個季度真正持續下去。過了一段時間，我們將在監管備案方面建立供應鏈，以便產品可以四處流動。

So if we get to a point where we have kind of sold our products in the U.S., that makes sense to be sold in the U.S., we will be able to ship products from the U.S. to international and vice versa. We want to set up the supply chain so that even at some stage we need more product in the U.S., we can import from Switzerland more products into the U.S. So we're trying to set up a supply chain that allows us to be very flexible and nimble to react to the needs of the marketplace. I hope that answered your question, Alec.

因此，如果我們達到了在美國銷售產品的程度，那麼在美國銷售是有意義的，我們將能夠將產品從美國運送到國際，反之亦然。我們希望建立供應鏈，以便即使在某個階段我們需要在美國提供更多產品，我們也可以從瑞士進口更多產品到美國。因此，我們正在嘗試建立一個供應鏈，使我們能夠非常靈活並能靈活應對市場需求。我希望這回答了你的問題，亞歷克。

Yes. Very helpful.

是的。很有幫助。

And our next question comes from the line of Hartaj Singh with Oppenheimer.

我們的下一個問題來自哈塔吉·辛格和奧本海默的對話。

Thanks for all of the data presented. Just a couple of quick questions. One is a non-COVID-related on CMV 1647. You've got a worldwide asset, you have worldwide rights, too. How are you thinking in terms of as you grow the organization to fund on a worldwide basis with -1273? Can you just talk a little bit about how that will help you with -1647 when the time comes to launch that and even prepare for worldwide trial with -1647?

感謝您提供的所有數據。只是幾個簡單的問題。其中一個是 CMV 1647 上與新冠病毒無關的內容。您擁有全球資產，也擁有全球權利。當您發展組織以在全球範圍內使用 -1273 提供資金時，您有何想法？您能否簡單談談這將如何幫助您在推出 -1647 時提供幫助，甚至為 -1647 的全球試驗做準備？

And then secondly, is this just wrong for us to assume that part of your initial revenues from -1273 to COVID-19 vaccine could be sort of one-offs depending on how governments order them versus kind of a more like-for-like basis comparison on a year-over-year basis? Any way to think about that going forward?

其次，我們假設從 -1273 到 COVID-19 疫苗的部分初始收入可能是一次性的，這是否是錯誤的，具體取決於政府如何訂購它們，而不是一種更類似的基礎同比比較？未來有什麼辦法可以考慮嗎？

Thank you, Hartaj. So on the, I would say, non-COVID organization, Stephen Hoge has spent a lot of time since the beginning of the pandemic to really focus on that. One of the things we've done to allow us as company to both deliver -1273 at kind of historic record time and not slow down the rest of the pipeline which, of course, is very important for Moderna and Moderna's future and for patients. Basically, Tal has refocused most of his time on -1273 and taking this product from literally a computer into Phase I, into Phase II and into completing successfully the COVE study and all the interaction with regulatory agencies around the world on the one hand. And then Stephen has really focused on the non-COVID portfolio. And so what we have done is we've been hiring quite a lot. If you look at our headcount numbers, we've been hiring quite a lot, and we're going to continue to do so into the next quarters so that we can have the right scale in terms of development, so that we don't slow down the development pipeline of a great asset like CMV or PCV or other asset because we don't have the right teams on the ground.

謝謝你，哈塔傑。因此，我想說，在非新冠疫情組織中，自疫情爆發以來，斯蒂芬·霍格（Stephen Hoge）花了很多時間來真正關注這一點。我們所做的事情之一是讓我們公司能夠以歷史記錄的時間交付 -1273，並且不會減慢其餘管道的速度，當然，這對於 Moderna 和 Moderna 的未來以及患者來說非常重要。基本上，Tal 已將大部分時間重新集中在 -1273 上，並將該產品從字面上的計算機帶入第一階段、第二階段，並成功完成 COVE 研究以及與世界各地監管機構的所有互動。然後斯蒂芬真正專注於非新冠投資組合。所以我們所做的就是招聘大量員工。如果你看看我們的員工人數，我們已經招聘了很多人，我們將在接下來的幾個季度繼續這樣做，這樣我們就可以在發展方面擁有適當的規模，這樣我們就不會由於我們沒有合適的團隊，因此會減慢CMV 或PCV 等重要資產或其他資產的開發流程。

And as we get closer to commercialization we'll, of course, hire people dedicated to that. We've already actually hired a Head of Marketing for CMV because it's very important. We believe, given there's no product on the market for CMV in terms of disease awareness, a lot of women do not know about CMV and what CMV could do to their pregnancy. And so we think there's a great opportunity while the Phase III is running to really drive up CMV awareness. And I think in a post-COVID world where people are going to be, I believe, are much more attuned to infectious disease. And given the similarity of outcome between Zika and CMV and given what happened in Latin America a few years ago, everybody is highly aware of Zika. And so I think there's a great opportunity for us to actually prepare the market to increase the speed of the uptake of CMV by preparing the market a few years before launch, which is what we are doing.

隨著我們越來越接近商業化，我們當然會聘請專門從事這方面工作的人員。實際上，我們已經為 CMV 聘請了一位營銷主管，因為這非常重要。我們相信，鑑於市場上沒有針對 CMV 的產品來提高疾病意識，很多女性不了解 CMV 以及 CMV 對懷孕的影響。因此，我們認為，在第三階段運行期間，有一個很好的機會來真正提高 CMV 意識。我認為，在後新冠疫情時代，人們將會更加適應傳染病。鑑於寨卡病毒和鉅細胞病毒結果的相似性，以及幾年前拉丁美洲發生的情況，每個人都對寨卡病毒高度關注。因此，我認為我們有一個很好的機會，通過在推出前幾年做好市場準備，來真正做好市場準備，以提高 CMV 的採用速度，這就是我們正在做的事情。

In terms of our revenues, as we described I think in the Q2 call, we really believe there's a pandemic phase of the COVID vaccine and then an endemic phase, which is going to be set up mostly on boosting. As has been discussed a lot in the medical community, we do not know across the different vaccines how long we're going to be working for. And so we believe, most probably, especially the elderly or people at high risk, we're going to want to boost their immune profile. We do not know yet if it's going to be once a year, once every 2 years, once every 3 years. Most probably, it will depend on different population. We have no really way to know that but to run the clinical experiments, which we are all doing across the industry. I could anticipate that different vaccine will have different duration of protection. And so indeed, I think you're thinking about it the right way, which I think there's going to be for quite a while, pandemic contracts that are going to be set up like some that we have set up to actually start vaccinating people. And then there's going to be a follow-up contract that I can anticipate for the boost. So that's kind of how we think about it. Does that make sense, Hartaj?

就我們的收入而言，正如我們在第二季度電話會議中所描述的那樣，我們確實相信新冠疫苗有一個大流行階段，然後是一個流行階段，該階段將主要建立在加強疫苗接種的基礎上。正如醫學界多次討論的那樣，我們不知道不同疫苗的效果能持續多久。因此，我們相信，最有可能的是，特別是老年人或高危人群，我們希望增強他們的免疫狀況。我們還不知道是每年一次、每兩年一次還是每三年一次。最有可能的是，這將取決於不同的人群。我們沒有辦法真正知道這一點，只能進行臨床實驗，我們整個行業都在這樣做。我可以預見不同的疫苗會有不同的保護期限。事實上，我認為你正在以正確的方式思考這個問題，我認為在相當長的一段時間內，大流行病合同將像我們為實際開始為人們接種疫苗而建立的一些合同一樣建立。然後將會有一份後續合同，我可以預期它會帶來提升。這就是我們的想法。哈塔傑，這有道理嗎？

Yes. Now that helps a lot, Stéphane.

是的。現在這很有幫助，斯特凡。

And our next question comes from the line of George Farmer with BMO Capital Markets.

我們的下一個問題來自 BMO 資本市場的 George Farmer。

I was wondering if you could comment on what happens if you don't hit the primary end point of this study, of the COVE study and you do hit meaningfully on secondary end points, which could be quite important. I mean certainly reducing severity of disease could be something regarded as meaningful. Have you thought about that?

我想知道您是否可以評論一下，如果您沒有達到本研究、COVE 研究的主要終點，但您確實達到了有意義的次要終點，這可能非常重要，那麼會發生什麼。我的意思是，降低疾病的嚴重程度肯定是有意義的。你有想過嗎？

And my second question is, if you do get an EUA, do -- does the existing supply agreement have come into play? Do you start drawing down on your inventory commitments following EUA? Or do you wait until you get full approval?

我的第二個問題是，如果您確實獲得了 EUA，現有的供應協議是否已經發揮作用？您是否在 EUA 後開始減少庫存承諾？還是要等到獲得完全批准？

So George, this is Tal. Interesting points you raised. Typically, if you don't hit the primary, you don't get to take credit from secondaries the way the stats are laid out. I think in this case, if there's biological possibility then, of course, we'd go and discuss with the agency what the data are looking like because I anticipate we will actually have the opportunity to cross it early. We may have those discussions ahead of time while more data is accumulating. And if we fail to hit it but the trial continue blinded, given I think the exigent circumstances, we can go and have a dialogue with the agency and what we've seen so far. But I'd say the proximal answer would still be the conservative one, which is if you don't hit the primary, it's very hard to take credit for secondaries. It's going to be up to the regulators.

喬治，這是塔爾。你提出的有趣的觀點。通常，如果你沒有達到主要目標，你就無法按照統計數據的方式從次要目標中獲得榮譽。我認為在這種情況下，如果存在生物學可能性，那麼我們當然會去與該機構討論數據是什麼樣的，因為我預計我們實際上將有機會儘早跨越它。在積累更多數據的同時，我們可能會提前進行這些討論。如果我們未能達成目標，但審判繼續盲目，考慮到緊急情況，我們可以去與該機構以及我們迄今為止所看到的情況進行對話。但我想說，最接近的答案仍然是保守的，也就是說，如果你沒有達到主要目標，就很難將功勞歸於次要目標。這將由監管機構決定。

I think the answer to your second question is an easier one. Yes, the supply agreement kicks in, and U.S. government, I would expect would start to take the supplies once we have an Emergency Use Authorization.

我認為你的第二個問題的答案更容易。是的，供應協議生效，我預計一旦我們獲得緊急使用授權，美國政府就會開始接收這些物資。

And our next question comes from the line of Alan Carr with Needham & Company.

我們的下一個問題來自李約瑟公司的艾倫·卡爾 (Alan Carr)。

Stepping away from COVID, you all mentioned the other month or last month that you'd like to revive that flu program. Wonder if you could give us some more details around that. Is this something that -- is it going to be built as a seasonal flu vaccine or something that you see as a universal vaccine? And if you can give us any updates on time lines around that.

拋開新冠疫情，你們都曾在上個月或上個月提到過希望恢復流感項目。不知道您能否給我們提供更多細節。這是一種季節性流感疫苗，還是一種你認為通用的疫苗？如果您能給我們提供有關時間線的任何更新。

Sure. This is Stephen. I'll take that. So what we announced last month is that we're looking at it strategically, and we're going to begin building a business in seasonal influenza. I'll remind you that we do have already clinical data in pandemic influenza from 2 different programs. And so we saw the ability to generate a protective immune response to influenza virus as well. We haven't provided clarity yet on when we expect that program to move into the clinic. We will, in the future, provide those updates as we get closer to that time.

當然。這是斯蒂芬.我會接受的。因此，我們上個月宣布，我們正在戰略性地考慮這一問題，我們將開始建立季節性流感業務。我要提醒您的是，我們確實已經擁有來自兩個不同項目的大流行性流感的臨床數據。因此我們也看到了對流感病毒產生保護性免疫反應的能力。我們還沒有明確說明我們預計該項目何時進入臨床。將來，我們將在臨近該時間時提供這些更新。

But we have suggested both that -- it's an interesting market to try and do better on because there's a substantial still unmet need in influenza, and we do think our platform can be differentiated for a couple of reasons. One, obviously, that we can bring many antigens to bear. And the second, the opportunity to do combinations, potentially combinations even with other viruses that might need seasonal boosting. And so we'll provide an update as soon as we declare the development candidates we normally do and move forward towards clinical development. But we're quite excited by that opportunity at this time.

但我們已經提出了這兩點——這是一個值得嘗試並做得更好的有趣市場，因為流感方面仍有大量未滿足的需求，而且我們確實認為我們的平台可以因幾個原因而與眾不同。第一，顯然，我們可以攜帶多種抗原。第二，有機會進行組合，甚至可能與其他可能需要季節性加強的病毒進行組合。因此，一旦我們宣布我們通常進行的開發候選藥物並推進臨床開發，我們將立即提供最新信息。但我們現在對這個機會感到非常興奮。

And our next question comes from the line of Umer Raffat with Evercore.

我們的下一個問題來自 Umer Raffat 和 Evercore 的關係。

I had a couple, if I may. First, maybe starting from an easier one. What's the cycle threshold you're using for the PCR positivity? Is it about 34? Second, if you could confirm if there have been any one-off cases of COVID infection for participants who got -1273 in Phase I or Phase II?

如果可以的話，我有一對。首先，也許從更容易的開始。您用於 PCR 陽性的循環閾值是多少？是34左右嗎？其次，您能否確認第一階段或第二階段獲得-1273的參與者是否存在一次性感染新冠病毒的病例？

And then finally, I know the slides mentioned rapid protection in lung and nose of nonhuman primates. But in the New England Journal data, we did see at least 1 primate at the 100 dose with detectable RNA on the nasal swab. So I guess what I'm getting at is, as a base case, despite the requirement of symptoms, is it reasonable to assume that we could actually see one-off cases of nasal swab test positive for COVID?

最後，我知道幻燈片提到了非人類靈長類動物肺部和鼻子的快速保護。但在《新英格蘭雜誌》的數據中，我們確實看到至少 1 只靈長類動物在服用 100 劑量後，其鼻拭子上可檢測到 RNA。所以我想我的意思是，作為一個基本案例，儘管有症狀的要求，但假設我們實際上可能會看到一次性的新冠病毒鼻拭子檢測呈陽性的病例是否合理？

Umer, let me take those questions. Cycle threshold, I don't think the number is meaningful because it's not the same number on different assays. It's part of the assay characteristics so I can't really comment because I don't believe you can compare those numbers across different assays.

烏默，讓我回答這些問題。循環閾值，我認為這個數字沒有意義，因為它在不同的檢測中不是相同的數字。這是測定特徵的一部分，所以我無法真正發表評論，因為我不相信您可以比較不同測定中的這些數字。

On the participants in the Phase II, I think we've had a case or 2, but since we're still blinded, I can't really comment on what that means.

關於第二階段的參與者，我認為我們已經有一兩個案例，但由於我們仍然盲目，我無法真正評論這意味著什麼。

The question on nasal swabs, yes. Well, first of all, in the primate, you're right, there was 1 primate with transient and relatively low levels in the nose and the rest were sterile. I think that when we talk about sterilizing immunity, I think that concept is confused by the high sensitivity that we have. So what do I mean by that? Well, if I'm immune and I've got IgGs and I've got IgAs as our data show we have and I'm walking down the street and somebody sneezes on me a whole bunch of SARS-CoV-2 and I'm on 49th Street, well, if somebody stops me on 50th Street and sticks a swab up my nose, they're probably going to see some detectable virus from that cloud I just inhaled a block ago. It doesn't mean that the antibodies aren't kicking in and the bars isn't getting cleared, it's a question of timing and sensitivity.

關於鼻拭子的問題，是的。嗯，首先，在靈長類動物中，你是對的，有一種靈長類動物的鼻子中存在短暫且相對較低的水平，其餘的都是不育的。我認為當我們談論滅菌免疫力時，我認為這個概念被我們的高敏感性所混淆。那麼我這是什麼意思呢？好吧，如果我有免疫力，而且我有IgG，而且我有IgAs，正如我們的數據顯示的那樣，我走在街上，有人對著我打噴嚏，然後我就感染了一大堆SARS- CoV-2。我在 49 街，好吧，如果有人在 50 街攔住我，並用棉籤塞進我的鼻子，他們可能會從我一個街區前剛剛吸入的雲中看到一些可檢測到的病毒。這並不意味著抗體沒有發揮作用，並且條形圖沒有被清除，這是一個時間和敏感性的問題。

So it depends then on how you measure and when you measure and what are the triggers for measuring. In our trial, we test people who raise their hand to say they've got a symptom and a reason to be tested. The only asymptomatic testing that occurs is really at day 1 and day 29 to make sure that we're excluding the right people are not confounding adverse events with actual disease. But short of that, we're not just randomly doing swab tests. So I hope that answers your question as it relates to detection.

因此，這取決於您如何測量、何時測量以及測量的觸發因素是什麼。在我們的試驗中，我們測試那些舉手說自己有症狀並有接受測試理由的人。唯一進行的無症狀檢測實際上是在第 1 天和第 29 天進行，以確保我們排除正確的人群，不會將不良事件與實際疾病混淆。但除此之外，我們不僅僅是隨機進行拭子測試。所以我希望這能回答您與檢測相關的問題。

And our next question comes from the line of Mani Foroohar with SVB Leerink.

我們的下一個問題來自 Mani Foroohar 和 SVB Leerink 的線路。

I know there's been a lot of folks on the COVID-19 program. Specifically, I wanted to dive in on math and financials a little bit. So did I hear it right that, for the quarter, about $10 million of what would otherwise be PP&E were expensed? And so with moving that back to CapEx, give us the base from which we go here. And secondarily on that, how should I think about the tempo of CapEx growing over the next 12 to 24 months, presuming a successful EUA and global commercialization? And then I have a follow-up question after this.

我知道有很多人參與了 COVID-19 計劃。具體來說，我想深入研究數學和金融。那麼，我沒聽錯吧，本季度，大約 1000 萬美元的 PP&E 支出被支出了？因此，將其轉移回資本支出，為我們提供我們前進的基礎。其次，假設 EUA 和全球商業化成功，我應該如何考慮未來 12 到 24 個月的資本支出增長速度？之後我還有一個後續問題。

Yes. So in terms of the capital deployment, if you look at the quarter 3, we had $10 million, which I mentioned that was -1273 related that was expensed. What also we invested was $12 million in the quarter which was capitalized, so $22 million in total. And I think that's a reasonable run rate. You'll see some increase here as we finish the year, and we trend up on investing in preparation for launch and the full capacity that we're putting in place.

是的。因此，就資本部署而言，如果你看一下第三季度，我們有 1000 萬美元，我提到過，這與 -1273 相關，已支出。我們在本季度還投資了 1200 萬美元，已資本化，因此總計 2200 萬美元。我認為這是一個合理的運行率。當我們今年結束時，您會在這裡看到一些增長，並且我們傾向於投資於啟動準備和我們正在部署的全部產能。

As that continues into next year, I think it's fair to understand that the capital deployment is going to increase somewhat, including the possibility in the fourth quarter of additional expensed capital to the extent it's deployed prior to the approval, which we do expect more to happen.

隨著這種情況持續到明年，我認為可以公平地理解資本部署將有所增加，包括第四季度在批准之前部署額外支出資本的可能性，我們確實預計更多發生。

And then if I may, also keep in mind the inventory expensing, which is not strictly capital investment, but the acquisition of raw materials and the cost of production. And of course, we're ramping that production in anticipation of an approval and therefore, it's quite likely that we'll have a fairly significant amount of expensed inventory occurring in Q4 prior to approval. And as you would understand, the impact of that is that as we start commercializing product post approval, the cost of that product will be essentially 0 from a cost of goods perspective until we've sold through that inventory that we produced prior to approval.

然後，如果可以的話，我還請記住庫存費用，嚴格來說，這不是資本投資，而是原材料的採購和生產成本。當然，我們正在提高產量以期獲得批准，因此，在批准之前的第四季度，我們很可能會產生相當大量的費用庫存。正如您所理解的，其影響是，當我們在批准後開始將產品商業化時，從商品成本的角度來看，該產品的成本基本上為零，直到我們售完批准前生產的庫存為止。

Okay. That's really helpful. And then hopping over on to the non-COVID pipeline. I may have missed it if it was mentioned. What's the time line to get the next slug of data from the OX40 ligand program? And when should we think about having a reasonable number of patients with that asset on top of a PD-1, on an approved PD-1 therapeutic?

好的。這真的很有幫助。然後跳到非新冠疫情管道上。如果提到的話我可能會錯過它。從 OX40 配體計劃獲取下一批數據的時間是多少？我們什麼時候應該考慮讓合理數量的患者在 PD-1 基礎上接受已批准的 PD-1 治療？

Let me try and take that. This is Tal. So it's oncology and data, I think, is determined to buy not just patient and accrual, but the events that happen on trial. And so it's really hard for me to predict, which is why we've been very clear on how many patients we have and where are we. I think the next tranche of data, I would anticipate, will be once we have a sufficient number of these patients with ovarian cancer on trial, and that is already in combination with PD-L1 blocker. So that should be informative for response rates once we have sufficient -- patients with sufficient follow-up.

讓我嘗試一下。這是塔爾。因此，我認為，腫瘤學和數據不僅決定購買患者和應計費用，還決定購買試驗中發生的事件。所以我真的很難預測，這就是為什麼我們非常清楚我們有多少患者以及我們在哪裡。我認為，我預計，一旦我們有足夠數量的卵巢癌患者接受試驗，並且已經與 PD-L1 阻斷劑聯合使用，就會得到下一批數據。因此，一旦我們有足夠的患者進行足夠的隨訪，這應該為反應率提供信息。

Great. That's helpful. And as a final question, I'll go back to financials. Obviously, the stock has been quite volatile over the course of this year as have many of your peers. Given that and given that you continue to build out your infrastructure and headcount, anticipation of expanding the pipeline and launching commercially, presuming EUA for COVID-19. How should I think about modeling or how should we think about modeling stock-based compensation relative to the overall R&D expense, SG&A expense? Would the portion to go up as you start to have more of a sales force, will go down as you get scale? Just how should we think about that, either in absolute terms as a proportion of spend? Just how should we think about modeling it the next, say, 12 months?

偉大的。這很有幫助。作為最後一個問題，我將回到財務問題。顯然，今年以來該股的波動相當大，許多同行也是如此。鑑於此，並考慮到您將繼續建設基礎設施和人員數量，預計將擴大管道並進行商業啟動，並假定適用於 COVID-19 的 EUA。我應該如何考慮建模，或者我們應該如何考慮相對於總體研發費用、SG&A 費用的基於股票的薪酬建模？當你開始擁有更多的銷售隊伍時，這個比例會上升，當你擴大規模時，這個比例會下降嗎？我們應該如何看待這個問題，無論是從支出的絕對比例來看？我們應該如何考慮在接下來的 12 個月內對其進行建模？

That's a very good question. And I guess I'd have to get back to you. I guess I'd start with a point of view that the trend would be stable, but we'll have to get back to you on that.

這是一個非常好的問題。我想我必須回复你。我想我首先會認為趨勢將是穩定的，但我們必須就此回复您。

Our last question comes from the line of Navin Jacob with UBS.

我們的最後一個問題來自瑞銀集團 (UBS) 的納文·雅各布 (Navin Jacob)。

This is [Alanna] on for Navin. So from what you've seen in your nonhuman primate studies, what impact on prevention of infection through the viral colonization and viral transmission do you expect to see from -1273? And then secondly, sort of a broader question is do you think that your vaccine or any vaccine in general will be able to deliver sterilizing immunity?

這是 Navin 的[Alanna]。那麼，根據您在非人類靈長類動物研究中看到的情況，您預計 -1273 對通過病毒定植和病毒傳播預防感染有何影響？其次，一個更廣泛的問題是，您認為您的疫苗或任何一般疫苗能夠提供滅菌免疫力嗎？

Yes. So that's a good question. Let me tell you how I think about it. Again, as I alluded before, I think the concept of sterilizing immunity is a function of how you actually test for it. Will we able to demonstrate prevention of infection, at least as measured by serology, which is to say, maybe somebody saw a little bit of the virus, but actually the antibodies kicked in and they never established enough to demonstrate antibodies against the other parts of the virus, the nuclear capsid. That's actually what we will be measuring in the Phase III as a way to show protection for asymptomatic infection.

是的。這是一個好問題。讓我告訴你我是怎麼想的。再次，正如我之前提到的，我認為消除免疫力的概念取決於您實際測試的方式。我們是否能夠證明對感染的預防，至少通過血清學來衡量，也就是說，也許有人看到了一點病毒，但實際上抗體開始發揮作用，而且它們從未建立足夠的抗體來證明針對病毒其他部分的抗體病毒，核衣殼。這實際上是我們將在第三階段測量的，作為顯示對無症狀感染的保護的一種方式。

I'm hopeful that we will be able to demonstrate that. I anticipate that -- I mean, just on first principles. What is the hardest thing for a vaccine to do? It's to sterilize. What's the next hardest? It's to prevent asymptomatic. What's the easiest? It's probably to prevent the most severe disease. And so that's how I think about the order of expectations. But I think what you're really getting at is what is going to be the ability of this vaccine to prevent transmission. And I think because I don't anticipate any easy direct measure of this, we're going to have to do some math once we see the data. I expect that if people get less and certainly less severe sick, they will be spreading less because I think there is -- while we have asymptomatic spread, we also have symptomatic spread.

我希望我們能夠證明這一點。我預計——我的意思是，只是基於首要原則。疫苗最難做到的是什麼？是為了消毒。接下來最難的是什麼？是為了預防無症狀感染者。什麼是最簡單的？這可能是為了預防最嚴重的疾病。這就是我對期望順序的看法。但我認為你真正要了解的是這種疫苗預防傳播的能力。我認為，因為我預計不會有任何簡單的直接衡量方法，所以一旦我們看到數據，我們就必須做一些數學計算。我預計，如果人們的病情減少，而且病情肯定不那麼嚴重，他們的傳播就會減少，因為我認為，雖然我們有無症狀傳播，但我們也有有症狀傳播。

And so -- and in fact, I think the higher the symptoms at least earlier in the disease, potentially the more firewall shedding you see. So that's a complicated equation that, I think in a nutshell, is going to be very hard to answer directly through some concrete measurement in the trial. What we will hope to show is that we prevent asymptomatic infection based on serology. We will clearly hope to show prevention of symptomatic infection that's the primary end point. And based on first principles, which by the way, Phil Krause from FDA alluded to and agreed with last Thursday, one would anticipate that if you prevent symptomatic disease, you should -- it should be even clearer that you're preventing the more severe manifestations.

因此，事實上，我認為至少在疾病早期，症狀越嚴重，你看到的防火牆脫落可能就越多。簡而言之，這是一個複雜的方程，很難通過試驗中的一些具體測量來直接回答。我們希望展示的是，我們是根據血清學來預防無症狀感染的。我們顯然希望證明預防症狀感染是主要終點。順便說一句，FDA 的菲爾·克勞斯(Phil Krause) 上週四提到並同意這一基本原則，根據首要原則，人們會預計，如果你預防有症狀的疾病，你應該——更清楚的是，你正在預防更嚴重的疾病表現形式。

Thank you. And that concludes today's question-and-answer session. I would now like to turn the call back to Stéphane for any closing remarks.

謝謝。今天的問答環節到此結束。現在我想將電話轉回給 Stéphane，讓其發表結束語。

Great. Thank you, operator. Well, thank you, everybody, for your time and your question and your support. Have a wonderful day, and speak soon. Stay safe, everybody. Bye.

偉大的。謝謝你，接線員。好的，謝謝大家的時間、提問和支持。祝你有美好的一天，很快就會說話。大家注意安全。再見。

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

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。