莫德納 (MRNA) 2019 Q4 法說會逐字稿

Good morning.

早安.

And welcome to Moderna's Fourth Quarter and Full Year 2019 Conference Call.

歡迎參加 Moderna 2019 年第四季度和全年電話會議。

(Operator Instructions) Please be advised that the call is being recorded.

（操作員說明）請注意，通話正在錄音。

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

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

Please proceed.

請繼續。

Thank you, operator.

謝謝你，接線員。

Good morning, everyone.

大家，早安。

On today's call, we will discuss Moderna's fourth quarter and full year 2019 business update and financial results.

在今天的電話會議上，我們將討論 Moderna 2019 年第四季度和全年的業務更新和財務業績。

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.

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。

Speaking on today's call are Stéphane Bancel, our Chief Executive Officer; Tal Zaks, our Chief Medical Officer; Stephen Hoge, our President; and Lorence Kim, our Chief Financial Officer.

我們的首席執行官 Stéphane Bancel 在今天的電話會議上發言； 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洛倫斯·金 (Lorence Kim)。

Before we begin, I would like to remind everyone that this conference call will include forward-looking statements.

在開始之前，我想提醒大家，本次電話會議將包含前瞻性陳述。

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.

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，了解可能導致我們的實際業績和結果與這些前瞻性聲明中明示或暗示的結果存在重大差異的重要風險因素。

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.

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.

謝謝你，拉維娜。

And good morning, everyone.

大家早上好。

As you know, we believe mRNA has the potential to be a new class of medicines with the opportunity to address many unmet medical needs.

如您所知，我們相信 mRNA 有潛力成為一類新型藥物，有機會解決許多未滿足的醫療需求。

Given the unknowns of working with a new technology, we have been laser-focused on managing risk: technology risk, biology risk, execution risk and financing risk.

考慮到使用新技術的未知性，我們一直專注於管理風險：技術風險、生物風險、執行風險和融資風險。

2019 was an important inflection year for Moderna.

2019年對於Moderna來說是重要的轉折年。

We reported clinically validating data from key programs in 2 of our modalities, prophylactic vaccines on the left and systemic secreted and cell surface therapeutics on the right, data that we believe fundamentally changed the risk profile of each of these 2 modalities that we now call core modalities.

我們報告了我們兩種模式中關鍵項目的臨床驗證數據，左邊是預防性疫苗，右邊是全身分泌和細胞表面治療，我們相信這些數據從根本上改變了這兩種模式的風險狀況，我們現在稱之為核心模式方式。

As a result, our strategy is to double down in these 2 core modalities with many important medicines.

因此，我們的策略是在這兩種核心模式上加倍投入許多重要藥物。

We have already announced 5 new development candidates in these core modalities since January 13 at the JPMorgan Conference, 3 new development candidates in infectious disease prophylactic vaccines and 2 in the systemic secreted and cell surface therapeutic modalities.

自1 月13 日摩根大通會議以來，我們已經宣布了這些核心模式的5 個新開發候選項目，其中傳染病預防疫苗領域有3 個新開發候選項目，全身分泌和細胞表面治療模式有2 個新開發候選項目。

While we've doubled down in core modalities, we are still more than ever interested in understanding the potential of our mRNA technology in our exploratory modalities: cancer vaccines, intratumoral immuno-oncology, localized regenerative therapeutics and systemic intracellular therapeutics.

雖然我們在核心模式上加倍努力，但我們仍然比以往任何時候都更有興趣了解我們的 mRNA 技術在探索模式中的潛力：癌症疫苗、腫瘤內免疫腫瘤學、局部再生治療和系統細胞內治療。

So when we think about this, we have 2 distinct businesses.

因此，當我們思考這個問題時，我們有兩個不同的業務。

This is a significant point in our strategy.

這是我們戰略中的一個重要點。

Core modalities, where we want to scale and invest; exploratory modalities where we are waiting for clinical data to decide on the path forwards.

核心模式，我們想要擴大規模和投資的領域；我們正在等待臨床數據來決定前進道路的探索模式。

So stepping back, I would like to share with you the progression of the company toward a new class of medicines.

因此，退一步，我想與大家分享公司在新型藥物方面的進展。

In the early days of Moderna's history, our goal was to enter the clinic safely.

在 Moderna 歷史的早期，我們的目標是安全進入診所。

We spent years investing and developing mRNA science, formulation delivery and manufacturing.

我們花了數年時間投資和開發 mRNA 科學、配方交付和製造。

The company pivoted out of that growth phase when we entered the clinic with our H10 influenza vaccine in December 2015.

當我們於 2015 年 12 月將 H10 流感疫苗進入臨床時，公司就擺脫了這個增長階段。

In the clinic, our next goal was to learn how well our technology was working or not.

在診所中，我們的下一個目標是了解我們的技術是否有效。

We explored our technologies across 6 different modalities.

我們通過 6 種不同的方式探索了我們的技術。

We tested 16 different molecules in the clinic in a short 4-year period.

我們在短短 4 年的時間裡在診所測試了 16 種不同的分子。

In 2019, we generated important data in 2 of these 6 modalities and identified our first 2 core modalities, infectious disease prophylactic vaccines and systemic secreted and cell surface therapeutics.

2019 年，我們在這 6 種模式中的 2 種中生成了重要數據，並確定了我們的前 2 種核心模式：傳染病預防性疫苗以及系統分泌和細胞表面治療。

We're entering the new phase of the company's development.

我們正在進入公司發展的新階段。

Our goal for this next phase of our history is to find multiple BLAs while continuing to explore on our clinical programs in our 4 exploratory modalities, with support to invest aggressively in our science, including inventing new modalities such as our ongoing collaboration with Vertex.

我們下一階段的目標是找到多個 BLA，同時繼續以 4 種探索模式探索我們的臨床項目，並支持積極投資於我們的科學，包括發明新的模式，例如我們與 Vertex 的持續合作。

We were fortunate to be able to close the financing earlier this year so we can maximize the potential to create value and manage risk.

我們很幸運能夠在今年早些時候完成融資，這樣我們就可以最大限度地發揮創造價值和管理風險的潛力。

Once we file multiple BLAs, our goal will be to scale the company and commercialize a large portfolio of mRNA medicines.

一旦我們提交了多個 BLA，我們的目標將是擴大公司規模並將大量 mRNA 藥物商業化。

Now Tal will take you through our prophylactic vaccine programs.

現在，塔爾將帶您了解我們的預防性疫苗計劃。

Thank you, Stéphane, and good morning, everyone.

謝謝你，斯特凡，大家早上好。

I'll start with a quick reminder on the data generated to date with our vaccines.

首先，我將快速提醒一下我們的疫苗迄今為止生成的數據。

In over 1,000 healthy volunteers and 6 positive Phase I data sets to date, we have observed a safety profile consistent with the safety of marketed vaccines and the ability to elicit an immune response in the form of neutralizing antibodies.

迄今為止，在超過 1,000 名健康志願者和 6 個陽性 I 期數據集中，我們觀察到與市售疫苗的安全性一致的安全性，以及以中和抗體形式引發免疫反應的能力。

Updates for the ongoing programs are shown on this slide.

此幻燈片顯示了正在進行的計劃的更新。

The CMV Phase II dose confirmation study is enrolling well.

CMV II 期劑量確認研究招募情況良好。

We completed the second dose cohort and are close to completing the third one.

我們完成了第二個劑量組，並且即將完成第三個劑量組。

We now expect data readout to come in the third quarter of this year.

我們現在預計數據將於今年第三季度公佈。

Our hMPV/PIV3 combination respiratory vaccine has started the age de-escalation study, and Merck is on track with their RSV program in adults.

我們的 hMPV/PIV3 組合呼吸道疫苗已開始年齡遞減研究，默克 (Merck) 的成人 RSV 項目也步入正軌。

Zika is also going well as 3 of the 4 dose cohorts have completed enrollment.

寨卡病毒也進展順利，4 個劑量組中的 3 個已經完成入組。

Our 3 new development candidates announced recently are vaccines against pediatric RSV, mRNA-1345, Epstein-Barr virus, or EBV, mRNA-1189, and our vaccine against the novel 2019 coronavirus, mRNa-1273.

我們最近宣布的 3 種新開發候選疫苗是針對兒科 RSV mRNA-1345、EB 病毒或 EBV mRNA-1189 的疫苗，以及針對 2019 年新型冠狀病毒 mRNA-1273 的疫苗。

Stephen will take you through each of these candidates in a minute.

斯蒂芬將在一分鐘內帶您了解這些候選人。

CMV is an unmet need as there aren't any approved vaccines, and the burden of disease from CMV infection is significant.

CMV 是一個未得到滿足的需求，因為沒有任何批准的疫苗，並且 CMV 感染帶來的疾病負擔是巨大的。

Of the 25,000 newborns in the U.S. affected each year, 20% will have permanent neuro developmental disabilities.

美國每年有 25,000 名新生兒受到影響，其中 20% 會出現永久性神經發育障礙。

And the spectrum of sequelae range from hearing loss, vision loss, microcephaly and even mortality in 10% to 30% of the severely affected infants.

後遺症範圍包括聽力喪失、視力喪失、小頭畸形，甚至 10% 至 30% 的嚴重受影響嬰兒死亡。

We believe our gB and pentamer vaccine has the potential to prevent CMV infection and help thousands of newborns avoid these sequelae.

我們相信我們的 GB 和五聚體疫苗有潛力預防鉅細胞病毒感染，並幫助成千上萬的新生兒避免這些後遺症。

On Slide 16, I'll review the most recent data from our CMV program.

在幻燈片 16 上，我將回顧我們 CMV 計劃的最新數據。

In January of this year, we shared the 7-month interim data.

今年1月份，我們分享了7個月的中期數據。

The safety has been generally well-tolerated, and we've not seen any related serious adverse events.

安全性總體上耐受性良好，我們沒有看到任何相關的嚴重不良事件。

Immunogenicity data continues to confirm earlier interim data from the trial and continues to exceed our expectations.

免疫原性數據繼續證實早期試驗的中期數據，並繼續超出我們的預期。

Specifically, we continue to see higher neutralizing antibody titers in seronegatives and seropositives in both epithelial and fibroblast assays.

具體來說，我們在上皮細胞和成纖維細胞檢測中繼續看到血清陰性和血清陽性的中和抗體滴度較高。

If you look at those who have never had CMV, the seronegative group, after the third vaccination, they had neutralizing titers against epithelial cells that were more than tenfold higher than the levels seen in seropositives at baseline.

如果你觀察那些從未感染過 CMV 的人（血清陰性組），在第三次接種疫苗後，他們的上皮細胞中和滴度比基線時血清陽性者的水平高十倍以上。

We also saw a nice increase in titers against the fibroblasts.

我們還看到針對成纖維細胞的效價顯著增加。

Even in seropositives, people who have been infected, our vaccine is able to boost them twenty to fortyfold higher above baseline level after the third vaccination, and we see early evidence of durability out to 12 months.

即使是血清反應呈陽性的感染者，我們的疫苗在第三次疫苗接種後也能將其水平提高到基線水平的20 至40 倍，而且我們看到了其持久性長達12 個月的早期證據。

These data are what's behind our optimism and belief that we can take this vaccine all the way through to prevent infections in newborns.

這些數據支撐著我們的樂觀態度和信念，我們相信我們可以一直服用這種疫苗來預防新生兒感染。

As mentioned earlier, our Phase II dose confirmation study is enrolling well and is currently enrolling the last dose cohort.

如前所述，我們的 II 期劑量確認研究招募情況良好，目前正在招募最後一個劑量組。

We now expect data from the first interim analysis in the third quarter of this year.

我們現在預計今年第三季度的第一次中期分析數據。

Preparation for the Phase III trial that we anticipate will include less than 8,000 participants, including women of childbearing age, are underway.

III 期試驗的準備工作正在進行中，預計將有不到 8,000 名參與者，其中包括育齡婦女。

An early estimate of the cost of this trial is in the range of $200 million to $250 million.

初步估計該試驗的成本在 2 億至 2.5 億美元之間。

Now as an opportunity for us, CMV is clearly a blockbuster opportunity.

現在對於我們來說，CMV 顯然是一個重磅機會。

We estimate annual peak sales for a CMV vaccine to be in the range of $2 billion to $5 billion, in line with the estimates of others in the field.

我們估計 CMV 疫苗的年度峰值銷售額將在 20 億至 50 億美元之間，這與該領域其他人的估計一致。

Assuming an average selling price like GARDASIL, a relevant comparator here, we estimate gross margins of about 90% and EBIT margins of approximately 50%.

假設平均售價類似於 GARDASIL（這裡的相關比較器），我們估計毛利率約為 90%，息稅前利潤率約為 50%。

We're excited about the progress towards this opportunity, supported by the fact that just 1 of the antigens in our vaccine, the gB, when encoded for in a traditional recombinant technology in the past, had already shown a 50% efficacy, which was demonstrated by Sanofi several years ago.

我們對這一機會所取得的進展感到興奮，事實證明，我們的疫苗中只有一種抗原，gB，在過去以傳統重組技術編碼時，已經顯示出 50% 的功效，這是賽諾菲幾年前就證明了這一點。

We believe that targeting both the pentamer and gB antigens, as our CMV vaccine does, will be additive to the vaccine's efficacy.

我們相信，像我們的 CMV 疫苗一樣，針對五聚體和 gB 抗原將增強疫苗的功效。

As a reminder, our CMV vaccine, mRNA-1647, is wholly owned by us.

提醒一下，我們的 CMV 疫苗 mRNA-1647 由我們全資擁有。

Let me transition it to Stephen to talk about our new development candidates.

讓我把它轉給斯蒂芬來談談我們的新開發候選者。

Thank you, Tal.

謝謝你，塔爾。

I want to start by introducing 3 development candidates in our vaccine -- prophylactic vaccines modality that we've recently announced earlier this month.

我想首先介紹我們的疫苗中的 3 個候選疫苗——我們本月早些時候剛剛宣布的預防性疫苗模式。

The first is against Epstein-Barr virus.

第一個是針對 Epstein-Barr 病毒。

And just want to pause for a moment and give you an overview of the disease.

只是想暫停一下，讓您大致了解一下這種疾病。

So Epstein-Barr virus is a member of the herpes family that includes CMV and is spread through bodily fluids, mostly in the young children and adolescents.

因此，EB 病毒是包括 CMV 在內的皰疹家族的一員，通過體液傳播，主要在幼兒和青少年中傳播。

EBV is a major cause of a wide range of diseases, but is the leading cause of infectious mononucleosis in the United States, accounting for almost 1 million cases annually.

EBV 是多種疾病的主要原因，也是美國傳染性單核細胞增多症的主要原因，每年約有 100 萬例病例。

Infectious mononucleosis can debilitate patients for weeks to months, and in rare cases, can lead to hospitalization and even splenic rupture.

傳染性單核細胞增多症會使患者虛弱數周至數月，在極少數情況下，可能導致住院甚至脾破裂。

EBV infection is also associated with a range of other disorders, including lymphoproliferative disorders, cancers and autoimmune diseases.

EBV 感染還與一系列其他疾病有關，包括淋巴增殖性疾病、癌症和自身免疫性疾病。

I mean, for instance, it is associated with a significant increase in risk of multiple sclerosis.

我的意思是，例如，它與多發性硬化症風險的顯著增加有關。

There are currently no approved vaccines for EBV.

目前還沒有批准的 EB 病毒疫苗。

So our vaccine candidate, mRNA-1189, is designed to provide broad protection against EBV infection and infectious mononucleosis.

因此，我們的候選疫苗 mRNA-1189 旨在提供針對 EBV 感染和傳染性單核細胞增多症的廣泛保護。

EBV has a number of surface proteins on its envelope, including gp350, a trimeric complex of gp42, gH and gL, a dimeric complex and also gB.

EBV 的包膜上有許多表面蛋白，包括 gp350、gp42、gH 和 gL 的三聚複合物、二聚複合物以及 gB。

All of those antigens are important for infecting a range of different cell types, but particularly, B cells and epithelial cells.

所有這些抗原對於感染一系列不同的細胞類型都很重要，尤其是 B 細胞和上皮細胞。

Now vaccination against only one of those antigens, gp350, which provides only partial B cell protection, reduced the rate of infection in a prior study by up to 7 -- reduced the rate of infectious mononucleosis in a prior study by up to 78%, but it did not prevent the rate of infection.

現在，僅針對其中一種抗原gp350 進行疫苗接種，該抗原僅提供部分B 細胞保護，在先前的研究中將感染率降低了7%，在先前的研究中將傳染性單核細胞增多症的發生率降低了78%，但這並沒有阻止感染率。

We believe that the combination of multiple antigens, gp350, plus antigens for -- or gp42/gH/gL and gB will provide an opportunity for broader protection both at B cells and epithelial cells, very analogous to our approach with the cytomegalovirus vaccine.

我們相信，多種抗原（gp350）加上抗原（或 gp42/gH/gL 和 gB）的組合將為 B 細胞和上皮細胞提供更廣泛的保護，這與我們使用鉅細胞病毒疫苗的方法非常相似。

Now we estimate that the opportunity is quite substantial.

現在我們估計這個機會是相當大的。

Worldwide direct cost of EBV-linked infectious mononucleosis reached almost $500 million annually, and the indirect costs could exceed $1 billion.

全球每年因 EBV 相關傳染性單核細胞增多症造成的直接損失接近 5 億美元，間接損失可能超過 10 億美元。

But prevention of infection, EBV infection, in addition to the prevention of infectious mononucleosis, could represent a much more significant upside because of the associated increased risk in cancers and multiple sclerosis.

但是，除了預防傳染性單核細胞增多症之外，預防感染、EB 病毒感染可能具有更顯著的好處，因為癌症和多發性硬化症的風險會增加。

These will represent a long-term potential but are not currently a focus of our current clinical development plan.

這些將代表長期潛力，但目前不是我們當前臨床開發計劃的重點。

Heading now to our second recently announced program, which is for respiratory syncytial virus in the pediatric population, I want to pause and provide a little bit of an overview of the disease again.

現在轉到我們最近宣布的第二個計劃，該計劃針對兒科人群中的呼吸道合胞病毒，我想暫停一下並再次提供對該疾病的一些概述。

RSV is the leading cause of unaddressed severe lower respiratory tract disease and hospitalization in infants and young children worldwide.

RSV 是全球嬰幼兒嚴重下呼吸道疾病未得到解決和住院的主要原因。

It's a major cause of hospitalization in this country, accounting for up to 86,000 hospitalizations a year and over 2 million medically attended RSV infections in children under the age of 5. Globally, the burden of disease is even more substantial, with over 30 million episodes of acute lower respiratory tract infection annually.

它是該國住院的一個主要原因，每年導致多達86,000 例住院治療，並導致超過200 萬例5 歲以下兒童因RSV 感染而接受治療。在全球範圍內，這種疾病的負擔更加沉重，發病次數超過3,000 萬例每年發生急性下呼吸道感染。

And we estimate that the direct costs associated with pediatric RSV disease in the children under the age of 5 exceed $2 billion annually.

我們估計，5 歲以下兒童與兒科 RSV 疾病相關的直接成本每年超過 20 億美元。

So our target population for this vaccine is the young, under the age of 5 children for respiratory syncytial virus.

所以我們這款疫苗的目標人群是年輕人，5歲以下的呼吸道合胞病毒兒童。

There is currently no approved RSV vaccine in that population.

目前還沒有批准用於該人群的 RSV 疫苗。

Our candidate, mRNA-1345, encodes for a stabilized prefusion F glycoprotein, analogous to our other efforts in RSV vaccines.

我們的候選藥物 mRNA-1345 編碼穩定的融合前 F 糖蛋白，類似於我們在 RSV 疫苗方面的其他努力。

mRNA-1345 will use the same proprietary lipid nanoparticle as our hMPV/PIV3 vaccine, mRNA-1653 as well as the CMV vaccine that Tal just described.

mRNA-1345 將使用與我們的 hMPV/PIV3 疫苗、mRNA-1653 以及 Tal 剛剛描述的 CMV 疫苗相同的專有脂質納米顆粒。

And we believe that neutralizing antibodies elicited by 1345 will lead to a reduction of medically attended RSV disease in the very young.

我們相信 1345 引發的中和抗體將減少幼兒中就醫的 RSV 疾病。

And while that's exciting, we actually intend to combine 1345 with mRNA-1653 to create a combination pediatric vaccine -- respiratory vaccine, which will address over 3 million medically attended lower respiratory track and upper respiratory track infections annually in the U.S. alone.

雖然這令人興奮，但我們實際上打算將1345 與mRNA-1653 結合起來，創建一種聯合兒科疫苗——呼吸道疫苗，僅在美國每年就將解決超過300 萬人的下呼吸道和上呼吸道感染問題。

That combination of mRNA-1345 and 1653 would represent a significant opportunity to address unmet need.

mRNA-1345 和 1653 的組合將代表著解決未滿足需求的重要機會。

The current plan is to develop 1345 and 1653 independently in the near-term through their initial clinical studies, but we would combine them prior to registrational studies and ultimately advance a joint product.

目前的計劃是在短期內通過初步臨床研究獨立開發1345和1653，但我們會在註冊研究之前將它們結合起來，最終推出聯合產品。

Now the third vaccine that we announced earlier this month is our mRNA vaccine against the SARS CoV-2 virus, recently named the novel coronavirus that's associated with COVID-19 disease.

現在，我們本月早些時候宣布的第三種疫苗是針對 SARS CoV-2 病毒的 mRNA 疫苗，該病毒最近被命名為與 COVID-19 疾病相關的新型冠狀病毒。

mRNA-1273 is an mRNA vaccine that encodes for a prefusion stabilized form of the Spike protein of that novel coronavirus that had been selected by Moderna in collaboration with the National Institute of Allergy and Infectious Diseases, the vaccine -- and the Vaccine Research Center, which are both part of the NIH.

mRNA-1273 是一種 mRNA 疫苗，編碼新型冠狀病毒刺突蛋白的預融合穩定形式，該疫苗是由 Moderna 與國家過敏和傳染病研究所、疫苗研究中心合作選擇的，它們都是 NIH 的一部分。

The first clinical batch for our Phase I, including finishing and filling of vials, was completed on February 7. And earlier this week, that batch was shipped to the NIH for the Phase I study.

我們的第一階段臨床批次，包括完成和灌裝小瓶，於 2 月 7 日完成。本週早些時候，該批次被運送到 NIH 進行第一階段研究。

And NIAID will conduct that Phase I study under their own IND in the near term.

NIAID 將在近期根據自己的 IND 進行第一階段研究。

Now pivoting to our second core modality.

現在轉向我們的第二個核心模式。

Earlier this year, we did announce 2 additional programs in the autoimmune therapeutic area in our systemic secreted and cell surface therapeutics.

今年早些時候，我們確實在自身免疫治療領域宣布了 2 個額外項目，涉及我們的系統分泌和細胞表面治療。

And as we described them at JPMorgan, I won't go into great detail, but to briefly recap them here.

正如我們在摩根大通所描述的那樣，我不會詳細介紹它們，而是在這裡簡要回顧一下。

IL-2 -- our IL-2 program, mRNA-6231, encodes for a long-acting tolerizing IL-2.

IL-2——我們的 IL-2 程序 mRNA-6231 編碼長效耐受性 IL-2。

As you can see in the lower right-hand corner on this page, we've demonstrated that in nonhuman primates at a single subcutaneous injection of mRNA-6231 can lead to a substantial increase in T reg cells without increasing activated cells.

正如您在本頁右下角所看到的，我們已經證明，在非人類靈長類動物中，單次皮下注射 mRNA-6231 可以導致 T reg 細胞大幅增加，而不會增加活化細胞。

That provides an opportunity to reestablish immune balance across -- that might be relevant for a wide range of autoimmune diseases.

這提供了重建免疫平衡的機會——這可能與多種自身免疫性疾病有關。

There are a number of different recombinant IL-2 based therapeutics that have shown potential, and we will be advancing this program into the clinic in the near term.

有許多不同的基於重組 IL-2 的療法已顯示出潛力，我們將在短期內將該計劃推進到臨床。

Second program we announced earlier this year was PD-L1, mRNA-6981.

我們今年早些時候宣布的第二個項目是 PD-L1、mRNA-6981。

It's an mRNA-encoded PD-L1 to send a tolerizing signal to immune cells.

它是一種 mRNA 編碼的 PD-L1，可向免疫細胞發送耐受信號。

In this case, we are expressing PD-L1 on the myeloid antigen-presenting cell.

在這種情況下，我們在骨髓抗原呈遞細胞上表達 PD-L1。

And the purpose of that is to drive a tolerogenic phenotype, a reestablishment of immune homeostasis in effector cells, including T cells and B cells.

其目的是驅動耐受表型，即效應細胞（包括 T 細胞和 B 細胞）中免疫穩態的重建。

mRNA-6981 will be an IV infusion, using the same LNP as our mRNA-encoded antibody, mRNA-1944, that had previously been described.

mRNA-6981 將採用 IV 輸注，使用與我們之前描述的 mRNA 編碼抗體 mRNA-1944 相同的 LNP。

And in preclinical disease models across a wide range of autoimmune conditions, we've demonstrated ability to modify the disease as you can see on the lower right-hand corner, one example, which is collagen-induced arthritis.

在各種自身免疫性疾病的臨床前疾病模型中，我們已經證明了改變疾病的能力，如右下角所示，一個例子是膠原蛋白誘導的關節炎。

The first indication in which we're going to be bringing the PD-L1 program forward is in autoimmune hepatitis, a disease we see a compelling unmet need.

我們要推進 PD-L1 項目的第一個跡像是自身免疫性肝炎，我們認為這種疾病的需求尚未得到滿足。

Now with that, I'll turn it back over to Tal to talk about our other work in exploratory modalities.

現在，我將把它轉回塔爾，談談我們在探索模式方面的其他工作。

Thank you, Stephen.

謝謝你，斯蒂芬。

Let me just briefly review these modalities that we consider exploratory, but obviously make up a significant part of what we do in clinical research and give you a sense where we are in the prosecution of these programs.

讓我簡單回顧一下這些我們認為是探索性的模式，但顯然它們是我們臨床研究工作的重要組成部分，讓您了解我們在這些項目的實施過程中所處的位置。

Starting with the cancer vaccines.

從癌症疫苗開始。

Our personalized cancer vaccine, mRNA-4157, is in a randomized Phase II trial for the treatment of adjuvant melanoma, in the combination of PCV with KEYTRUDA against KEYTRUDA alone, and it's recruiting well.

我們的個性化癌症疫苗 mRNA-4157 正在進行一項隨機 II 期試驗，用於治療輔助性黑色素瘤，將 PCV 與 KEYTRUDA 聯合治療，以對抗單獨使用 KEYTRUDA，並且招募情況良好。

KRAS vaccine, mRNA-5671, is an ongoing Phase I study, and this one is led by Merck and it has a monotherapy as well as a combination with KEYTRUDA arm.

KRAS 疫苗 mRNA-5671 是一項正在進行的 I 期研究，該研究由默克公司領導，它有單一療法以及與 KEYTRUDA 臂的聯合療法。

Our intratumor immuno-oncology therapeutics, we have 3 programs in this modality.

我們的腫瘤內免疫腫瘤治療，在這種模式下我們有 3 個項目。

All of them are in combination with PD-1 inhibitors.

它們都與 PD-1 抑製劑聯合使用。

Dosing of patients is ongoing, and I look forward to the future to being able to demonstrate whether the ability to influence the immune system in this manner will be helpful to these patients.

對患者的給藥正在進行中，我期待未來能夠證明以這種方式影響免疫系統的能力是否會對這些患者有所幫助。

On the regenerative therapeutics modality, AstraZeneca is conducting a Phase IIa in patients with our mRNA that encodes for vascular endothelial growth factor.

在再生治療方式方面，阿斯利康正在利用我們編碼血管內皮生長因子的 mRNA 對患者進行 IIa 期臨床試驗。

And that's in patients that are undergoing CABG, coronary artery bypass grafting.

這是在接受 CABG（冠狀動脈旁路移植術）的患者中。

That study continues to enroll.

該研究仍在繼續招募。

In the systemic intracellular therapeutics, we have 2 INDs open now in both MMA and PA, methylmalonic acidemia and propionic acidemia.

在全身細胞內治療中，我們目前在 MMA 和 PA、甲基丙二酸血症和丙酸血症方面有 2 個 IND 開放。

I'm pleased to announce that the first patient in MMA has enrolled in this trial.

我很高興地宣布 MMA 的第一位患者已參加該試驗。

They're in the observation period right now.

他們現在正處於觀察期。

This trial is now open at 7 institutions in the United States, and we're continuing to look for additional patients to enroll while we follow this first patient closely.

該試驗現已在美國 7 家機構開放，我們將繼續尋找更多患者入組，同時密切關注第一位患者。

With that, let me turn it over to Lorence to describe the rest of our pipeline and where we go from here.

說到這裡，讓我把它交給洛倫斯來描述我們管道的其餘部分以及我們接下來的發展方向。

Thank you, Tal.

謝謝你，塔爾。

So on Slide 29, you see a graphic that represents our whole development pipeline as it stands today.

因此，在幻燈片 29 上，您可以看到一張圖表，它代表了我們目前的整個開發流程。

First and foremost, we're focused on the advancement and execution around this development pipeline.

首先也是最重要的，我們專注於圍繞該開發流程的推進和執行。

You heard 3 significant things from us today around the CMV vaccine, where the Phase III preparation is very much underway.

今天，您從我們這裡聽到了有關 CMV 疫苗的 3 件重要事情，該疫苗的 III 期準備工作正在進行中。

You heard the Phase II enrollment for that CMV vaccine is ahead of schedule.

您聽說 CMV 疫苗的二期註冊工作提前了。

And importantly, in Phase I, MMA has enrolled its first subject.

重要的是，在第一階段，MMA 已經招收了第一個科目。

So we're really focused on executing across the entire breadth of the pipeline.

因此，我們真正專注於在整個管道範圍內執行。

And then the other key thing you heard today is that the preclinical programs continue to grow.

您今天聽到的另一件重要事情是臨床前項目繼續增長。

And you will have heard that we announced in the first 2 months of the year 5 new development candidates.

您可能聽說過，我們在今年的前 2 個月宣布了 5 款新的開發候選產品。

This is indicative of the productivity that we expect out of the research platform.

這表明了我們對研究平台的預期生產力。

What this leads to on the next slide, it's a robust list of clinical data and next steps across the pipeline.

這將導致下一張幻燈片上出現的內容是一份完整的臨床數據列表和整個流程的後續步驟。

If you scan the page, you'll see a lot of readouts coming in the near term.

如果您掃描該頁面，您會看到近期會出現大量讀數。

We've guided for the CMV readout, the Phase II data with a 3-month interim analysis in the third quarter of this year and a Phase III start in 2021.

我們已在今年第三季度對 CMV 讀數、二期數據進行了為期 3 個月的中期分析，並於 2021 年啟動了三期數據。

And with the rest of the vaccines, you'll see a number of additional Phase I readouts that we would expect to occur as well as advancement of these newly nominated development candidates toward the clinic.

對於其餘的疫苗，您將看到我們預計會發生的許多額外的第一階段讀數，以及這些新提名的開發候選藥物向臨床的進展。

If you look at the next category of systemic secreted therapeutics, our antibody against Chikungunya will continue to progress through further development of a dose cohort and we'll continue to advance preclinical work towards IND filings.

如果你看看下一類全身分泌療法，我們針對基孔肯雅熱的抗體將通過劑量隊列的進一步開發繼續取得進展，我們將繼續推進 IND 申請的臨床前工作。

And you just heard from Tal that the rest of our programs will be progressively moving forward here towards clinical data.

您剛剛從塔爾那裡聽說，我們的其餘項目將逐步向臨床數據邁進。

On Slide 31 and today's press release, we reported our fourth quarter and full year 2019 financial results.

在幻燈片 31 和今天的新聞稿中，我們報告了 2019 年第四季度和全年財務業績。

Please note, these results are unaudited as of this call.

請注意，截至本次電話會議時，這些結果未經審計。

We'll be filing audited financials shortly with the 10-K.

我們很快就會向 10-K 提交經審計的財務數據。

We ended 2019 with cash, cash equivalents and investments of $1.26 billion.

2019 年末，我們的現金、現金等價物和投資為 12.6 億美元。

This compares to $1.69 billion at the end of 2018.

相比之下，2018 年底為 16.9 億美元。

Net cash used in operating activities was $459 million for 2019 compared to $331 million in 2018.

2019 年經營活動使用的現金淨額為 4.59 億美元，而 2018 年為 3.31 億美元。

And cash used for purchases of property and equipment was $32 million for 2019, a significant drop versus $106 million in 2018.

2019 年用於購買財產和設備的現金為 3200 萬美元，較 2018 年的 1.06 億美元大幅下降。

We placed our Norwood Moderna Technology Center manufacturing facility in service in mid-2018.

我們的 Norwood Moderna 技術中心製造工廠於 2018 年中期投入使用。

Revenue for Q4 2019 was $14 million compared to $35 million for Q4 2018.

2019 年第四季度的收入為 1400 萬美元，而 2018 年第四季度的收入為 3500 萬美元。

And for the full year, revenue was $60 million compared to $135 million in 2018.

全年收入為 6000 萬美元，而 2018 年為 1.35 億美元。

Recall that in January of 2019, we adopted the mandated revenue recognition standard, ASC 606, using a modified retrospective transition method applied to those contracts which weren't completed as of January 1, 2019.

回想一下，2019 年 1 月，我們採用了強制性收入確認標準 ASC 606，並採用了適用於截至 2019 年 1 月 1 日尚未完成的合同的修改後的追溯過渡方法。

And so the decreases in revenue are largely attributable to the adoption of this new revenue standard, together with the completion of the initial 4-year research period under the 2016 Merck agreement.

因此，收入的下降主要歸因於採用這一新的收入標準，以及 2016 年默克協議下最初 4 年研究期的完成。

Total revenue under the previous revenue recognition standard would have been $15 million for Q4 2019 and $95 million for the full year 2019.

根據之前的收入確認標準，2019 年第四季度的總收入為 1500 萬美元，2019 年全年的總收入為 9500 萬美元。

R&D expenses for Q4 2019 were $119 million compared to $150 million for Q4 2018.

2019 年第四季度的研發費用為 1.19 億美元，而 2018 年第四季度的研發費用為 1.5 億美元。

And for the full year 2019, R&D dollars were $496 million compared to $454 million in 2018.

2019 年全年研發費用為 4.96 億美元，而 2018 年為 4.54 億美元。

The decrease in Q4 was mainly due to a decrease in our in-licensing payments to Cellscript and its affiliates and a reduction of our lab supplies and materials.

第四季度的下降主要是由於我們向 Cellscript 及其附屬公司支付的許可費用減少以及我們的實驗室供應和材料的減少。

The increase for the full year 2019 was mainly driven by an increase in personnel-related costs, including stock-based comp, driven by an increase in the number of employees as well as higher clinical trial and manufacturing costs.

2019年全年的增長主要是由於員工數量增加以及臨床試驗和製造成本上升導致的人員相關成本（包括股票補償）的增加。

G&A expenses for Q4 were $26 million compared to $38 million in Q4 2018.

第四季度的一般管理費用為 2600 萬美元，而 2018 年第四季度為 3800 萬美元。

And for the full year, G&A expenses were $110 million compared to $94 million in 2018.

全年的一般管理費用為 1.1 億美元，而 2018 年為 9,400 萬美元。

The decrease in Q4 was primarily driven by a decrease in stock-based comp, mainly attributable to certain performance-based equity awards with vesting or commencement contingent on the IPO in 2018.

第四季度的下降主要是由於股票補償的下降，這主要是由於某些基於績效的股權獎勵，這些股權獎勵的歸屬或開始取決於 2018 年 IPO 的情況。

And the increase for the full year 2019 was mainly due to the additional costs of operating as a publicly traded company, including the increases in insurance, consulting and outside services and facility costs.

2019年全年的增長主要是由於作為上市公司運營的額外成本，包括保險、諮詢和外部服務以及設施成本的增加。

On the next slide, we show the progression of selected cash flow line items, namely our net cash used in operating activities and our purchases of property and equipment.

在下一張幻燈片中，我們顯示了選定現金流量項目的進展情況，即我們用於經營活動以及購買財產和設備的淨現金。

The table shows you our GAAP results by period with a total operating cash flow plus PP&E.

該表顯示了我們按期間劃分的 GAAP 結果以及總運營現金流加上 PP&E。

I'd point you primarily to the bar chart, which shows the quarter-by-quarter progression of this metric.

我主要向您指出條形圖，它顯示了該指標的季度進展。

And you'll see that our cash use shows a steady reduction through 2019.

您會發現我們的現金使用量在 2019 年穩步減少。

I would note that Q1 contained the impact of the last of the 3 licensing milestone payments we owed Cellscript, which is $22 million.

我要指出的是，第一季度包含了我們欠 Cellscript 的 3 個許可里程碑付款中最後一個的影響，即 2200 萬美元。

I don't expect this downward trend to continue to decline quarterly in 2020.

我預計這種下降趨勢在 2020 年不會繼續按季度下降。

But for the full year, you can see how we ended up overall flat versus 2019 when we thought about expectations, even with the advancement of our pipeline through the clinic.

但就全年而言，你可以看到，當我們考慮預期時，即使我們的管道在臨床中取得了進展，我們的整體表現與 2019 年持平。

And so the result -- we'll reiterate our guidance for 2020, which is that net cash used in operating activities and purchases of PP&E will total between $490 million and $510 million.

因此，我們將重申 2020 年的指導，即用於經營活動和採購 PP&E 的淨現金總額將在 4.9 億至 5.1 億美元之間。

That approximate $500 million of cash investment into our business is put into context on the next slide versus the cash that's available to us for investment.

我們業務中大約 5 億美元的現金投資將在下一張幻燈片中與我們可用於投資的現金進行比較。

Here, you see our year-end cash balance of $1.26 billion.

在這裡，您可以看到我們的年終現金餘額為 12.6 億美元。

And on top of that is the net proceeds of approximately $550 million from our equity offering, which includes the exercise of the underwriter's option to purchase additional shares that we anticipate to close later today.

除此之外，我們的股票發行淨收益約為 5.5 億美元，其中包括行使承銷商購買額外股票的選擇權，我們預計這些股票將於今天晚些時候完成。

And then as we've mentioned before, we have approximately $185 million in potential future grants available to us as well.

正如我們之前提到的，我們還有大約 1.85 億美元的未來潛在贈款可供我們使用。

And so these amounts sum up to $2 billion in available cash, which we expect to invest in our business.

因此，這些金額總計達 20 億美元的可用現金，我們預計將其投資於我們的業務。

And that represents a significant cash runway of multiple years.

這代表著多年的重要現金跑道。

I'll now hand it back to Stéphane to close.

現在我將把它交還給 Stéphane 來結束。

Thank you, Lorence and Stephen.

謝謝你們，洛倫斯和斯蒂芬。

On Slide 35, you can see an update on Moderna's file.

在幻燈片 35 上，您可以看到 Moderna 文件的更新。

Our company has never been stronger.

我們的公司從未如此強大。

Our pipeline.

我們的管道。

Preparing for CMV Phase III, 4 medicines in or preparing for Phase II, 11 Phase I trial is ongoing and 10 positive clinical readouts.

為 CMV III 期做準備，4 種藥物已進入或準備進入 II 期，11 項 I 期試驗正在進行中，10 項臨床結果呈陽性。

Our programs in development.

我們的計劃正在開發中。

7 vaccines, where there are no approved vaccines on the market.

7 疫苗，市場上尚無批准的疫苗。

Most of these vaccine candidates have multibillion-dollar annual peak sales opportunities.

大多數候選疫苗都有數十億美元的年度銷售高峰機會。

As I shared in our 2019 shareholder letter, we believe our innovative vaccines are going to be very large business for Moderna, with long-term, long-term annuity life opportunity and a high EBIT margin, 5 immuno-oncology drugs in the clinic, 5 rare disease programs with our first Phase I started for MMA, 2 autoimmune diseases program.

正如我在2019 年股東信中所分享的那樣，我們相信我們的創新疫苗將成為Moderna 的一項非常大的業務，具有長期、長期的年金人壽機會和高息稅前利潤率，5 種免疫腫瘤藥物已進入臨床，我們的MMA第一期項目啟動了5個罕見疾病項目，2個自身免疫性疾病項目。

The foundations of Moderna have never been stronger.

Moderna 的基礎從未如此堅固。

Our clinical experience is now more than 1,700 healthy volunteers and patients.

我們的臨床經驗現已超過 1,700 名健康志願者和患者。

The team is strong with more than 800 employees who care deeply about our mission and are proud of and energized by our progress.

該團隊擁有 800 多名員工，實力雄厚，他們非常關心我們的使命，並為我們的進步感到自豪和充滿活力。

I would like to thank our entire team.

我要感謝我們整個團隊。

I would like to extend a special thank you to those who made the coronavirus vaccine from sequence to shipping to NIH for Phase I dosing in only 42 days.

我要特別感謝那些製造冠狀病毒疫苗從測序到運送到 NIH 進行 I 期給藥僅用了 42 天的人。

And we are proud to be included with those many companies working on a possible response to this continuing global health emergency.

我們很自豪能夠與眾多公司一起致力於應對這一持續的全球衛生緊急情況。

Norwood, this a fully digital, fully integrated facility that enables the execution of our pipeline, all the way from raw materials to finished vials ready to ship to the clinic.

諾伍德，這是一個完全數字化、完全集成的設施，可以執行我們的管道，從原材料到準備運送到診所的成品小瓶。

We have great partners with AZ, Merck, Vertex, Defense or DARPA, BARDA, CEPI and the Gates Foundation.

我們與 AZ、Merck、Vertex、Defense 或 DARPA、BARDA、CEPI 和蓋茨基金會都有良好的合作夥伴。

As we said on November quarterly call, we are working on expanding that network of partners as we speak.

正如我們在 11 月季度電話會議上所說，我們正在努力擴大合作夥伴網絡。

With the financing, our grant capital and our cash balance, we're in a fortunate position to invest up to $2 billion towards building the leading mRNA company.

憑藉融資、我們的贈款資本和現金餘額，我們有幸投資高達 20 億美元來建立領先的 mRNA 公司。

We are thankful to our investors for their trust and partnership as we build this unique company.

我們感謝投資者在我們建立這家獨特公司的過程中給予的信任和合作。

For 2020, our priorities are very clear.

對於 2020 年，我們的優先事項非常明確。

Priority #1, execute on our development pipeline with a special focus on CMV Phase III start.

優先事項#1，執行我們的開發管道，特別關注 CMV 第三階段的啟動。

Priority #2 is creating new development candidates in the 2 core modalities.

優先事項#2 是在兩種核心模式中創造新的發展候選者。

We're already at 5 in the last 2 months only.

僅僅過去兩個月我們就已經達到了 5。

And priority #3 is to develop new development candidate in new modalities.

優先事項#3 是以新模式開發新的發展候選者。

Stay tuned here.

請繼續關注這裡。

As a reminder, these are the events we are hosting for analysts and investors in 2020.

提醒一下，這些是我們 2020 年為分析師和投資者舉辦的活動。

Our first Manufacturing and Digital Day is next week on Wednesday at our Norwood facility in Massachusetts.

我們的第一個製造和數字日將於下週三在馬薩諸塞州諾伍德工廠舉行。

A webcast will be available on our website.

我們的網站上將提供網絡廣播。

Juan Andres and his team will share many new insights, including how the team delivered coronavirus vaccine in 42 days from sequence to shipping.

胡安·安德烈斯 (Juan Andres) 和他的團隊將分享許多新見解，包括團隊如何在 42 天內交付冠狀病毒疫苗從測序到運輸。

Marcello Damiani and his team will share the progress since opening Norwood in July 2018 on the digital front, including use cases of artificial intelligence and machine learning.

Marcello Damiani 和他的團隊將分享自 2018 年 7 月諾伍德開業以來在數字領域取得的進展，包括人工智能和機器學習的用例。

We hope to host many of you for first Vaccine Day in New York City on April 14 for a deep dive into our mRNA vaccine modality.

我們希望能夠在 4 月 14 日在紐約市舉辦第一個疫苗日活動，以深入了解我們的 mRNA 疫苗模式。

We will discuss, among other things, clinical data, business model, how we think about value creation, capital allocation and probability of success of our mRNA vaccines.

除其他外，我們將討論臨床數據、商業模式、我們如何看待價值創造、資本配置和 mRNA 疫苗的成功概率。

In June, we look forward to hosting our first Science Day to be able to share with you the many progress the team has made on mRNA science and delivery since Science Day 2019.

6 月，我們期待舉辦首屆科學日，以便能夠與您分享自 2019 年科學日以來團隊在 mRNA 科學和遞送方面取得的許多進展。

In September, we'd also like to welcome you for our fourth R&D Day, where, as usual, in New York, we will review in detail clinical data.

九月，我們還歡迎您參加我們的第四個研發日，像往常一樣，我們將在紐約審查詳細的臨床數據。

As I shared in my introduction, Moderna is entering a new phase of its development as a company.

正如我在介紹中所分享的那樣，Moderna 作為一家公司正在進入其發展的新階段。

Our goals are clear.

我們的目標很明確。

One, file multiple BLAs and launch multiple medicines, which we own commercially; and two, continue to explore modalities in the clinic and invest in science.

第一，提交多個 BLA 並推出多種我們擁有的商業藥物；第二，繼續探索臨床模式並投資於科學。

We have 2 core modalities and are now laser-focused on filing multiple BLAs and then scaling Moderna to maximize our impact on patients.

我們有 2 種核心模式，現在專注於提交多個 BLA，然後擴展 Moderna，以最大限度地提高對患者的影響。

We are continuing to realize our vision.

我們正在繼續實現我們的願景。

We have got 12 innovative medicines currently in the clinic.

目前我們有12個創新藥物在臨床。

We are only getting started.

我們才剛剛開始。

mRNA is an information molecule.

mRNA是一種信息分子。

Because of that, we believe that the probability of technical success for our medicines from the lab to approval will be materially higher than traditional medicines.

正因為如此，我們相信我們的藥物從實驗室到批准的技術成功概率將大大高於傳統藥物。

Speed.

速度。

Our track record speaks louder than words.

我們的業績記錄勝於雄辯。

Coronavirus from sequence to shipping clinical-grade product, 42 days.

冠狀病毒從測序到運輸臨床級產品，42 天。

Evidence of greater capital efficiency relative to traditional recombinant technology is becoming apparent.

與傳統重組技術相比，資本效率更高的證據正在變得越來越明顯。

We can do new disease like EBV and pediatric RSV without additional capital invested.

我們可以研究 EBV 和兒科 RSV 等新疾病，而無需額外投入資金。

I have never been more optimistic about Moderna's future and potential since joining as employee #2 in 2011.

自 2011 年作為 2 號員工加入以來，我對 Moderna 的未來和潛力從未如此樂觀過。

I believe mRNA is going to be a new class of medicines, and I believe Moderna is the leading company in that field.

我相信 mRNA 將成為一類新的藥物，並且我相信 Moderna 是該領域的領先公司。

With $2 billion to invest, a great team, our science, our IP and the manufacturing site at Norwood, we will work to accelerate our leadership in the months and quarters to come.

憑藉 20 億美元的投資、一支優秀的團隊、我們的科學、我們的知識產權和諾伍德的製造基地，我們將努力在未來幾個月和幾個季度加速我們的領導地位。

We are excited by the opportunity to bring forward a new class of medicines for patients.

我們很高興有機會為患者推出新型藥物。

I'd like to thank the great team of Moderna employees working hard every day and sometimes every weekend to make this vision a reality.

我要感謝 Moderna 優秀的員工團隊，他們每天甚至每個週末都在努力工作，使這一願景成為現實。

I would like to thank the many people who participate in our clinical studies, including patients, healthy volunteers and physicians.

我要感謝參與我們臨床研究的許多人，包括患者、健康志願者和醫生。

I would also like to recognize all our commercial partners, our commercial partners who work with us and share our vision to deliver transformative medicines for patients.

我還要感謝我們所有的商業夥伴，與我們合作並分享我們為患者提供變革性藥物的願景的商業夥伴。

With that, we are now happy to take any questions.

至此，我們現在很樂意回答任何問題。

(Operator Instructions) Our first question is from Matthew Harrison from Morgan Stanley.

（操作員說明）我們的第一個問題來自摩根士丹利的馬修哈里森。

I guess 2 for me.

我猜對我來說是2。

So one, on coronavirus, and I think this is just so people understand.

第一，關于冠狀病毒，我認為這只是為了讓人們理解。

Could you just broadly comment?

您能泛泛地評論一下嗎？

It sounded like NIH needs to file an IND and then they would obviously start the clinical study.

聽起來 NIH 需要提交 IND，然後他們顯然會開始臨床研究。

What is your involvement at this point?

此時您的參與是什麼？

And are you taking any steps related to ramping manufacturing or any other steps related to this?

您是否正在採取任何與擴大生產相關的措施或與此相關的任何其他措施？

And then secondly, maybe just on CM -- well, actually, on MMA.

其次，也許只是在 CM 上——嗯，實際上，在 MMA 上。

Can you just talk about how enrollment is going for additional patients?

您能談談額外患者的入組情況嗎？

What sort of led you to be able to get that first patient in?

是什麼讓您能夠收治第一個病人？

And if you see promise in terms of being able to rapidly enroll additional patients.

如果您看到能夠快速招募更多患者的希望。

Thanks, Matthew.

謝謝，馬修。

This is Tal.

這是塔爾。

Let me take both of these questions.

讓我來回答這兩個問題。

As it relates to coronavirus, our part here was to manufacture and ship it.

由於它與冠狀病毒有關，我們在這裡的職責是製造和運輸它。

I think the trial now will be run by the NIH, and I defer to them to provide updates when they will.

我認為現在的試驗將由美國國立衛生研究院 (NIH) 進行，我會聽取他們的意見，以便他們隨時提供最新情況。

You asked about scale-up.

您詢問了擴大規模的問題。

I think we're looking at everything that it would take and how to actually get it done.

我認為我們正在考慮所需的一切以及如何真正完成它。

But we'll update everybody once we have a clear picture of that.

但一旦我們清楚地了解了這一點，我們就會向大家通報最新情況。

Obviously, this is a rapidly changing environment.

顯然，這是一個快速變化的環境。

On M&A enrollment, so right now, we've got one patient enrolled.

在併購登記方面，目前我們已經登記了一名患者。

We do not yet have a second and third, but we're actively working with sites to find them.

我們還沒有第二個和第三個，但我們正在積極與網站合作尋找它們。

The age barrier, I think, continues to be a difficult one.

我認為，年齡障礙仍然是一個困難。

We only have to find the first 3, so -- and then we can go down in age.

我們只需要找到前 3 個，然後我們就可以降低年齡了。

So I am confident that we will eventually, but I continue to have a dialogue with the agency on trying to reduce that need so that enrollment can be unhooked from that and we can get into the age population where we believe the greatest unmet need and potential for benefit is.

因此，我相信我們最終會做到這一點，但我會繼續與該機構進行對話，努力減少這種需求，以便入學可以擺脫這種需求，我們可以進入我們認為最大的未滿足需求和潛力的年齡人口為利益是。

So I'll update everybody as soon as we have progress in that field.

因此，一旦我們在該領域取得進展，我將立即向大家通報最新情況。

Our next question is from Ted Tenthoff of Piper Sandler.

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

Great.

偉大的。

And just following up on Matt's question first.

首先跟進馬特的問題。

What -- maybe you can just remind us again so that everybody understands it because I've getting a lot of questions on this.

什麼——也許你可以再次提醒我們，以便每個人都能理解，因為我收到了很多關於此的問題。

What is the process for licensure of a biothreat or pandemic vaccine such as coronavirus?

冠狀病毒等生物威脅或大流行疫苗的許可流程是什麼？

And then with respect to CMV, again, great progress just across the board here.

然後就 CMV 而言，這裡再次取得了全面的巨大進步。

Ultimately, what do you see as sort of the vaccination paradigm or timing of vaccinations for women of childbearing age?

最後，您認為育齡婦女的疫苗接種範例或疫苗接種時間是什麼？

Thanks, Ted.

謝謝，特德。

It's Tal.

是塔爾。

Let me take that.

讓我來吧。

I think what does it take to get licensure is an evolving field.

我認為獲得許可需要什麼是一個不斷發展的領域。

I mean the pathways to licensure are well-understood, and they encompass everything from finding surrogates of protection to demonstrating efficacy.

我的意思是，獲得許可的途徑是眾所周知的，它們涵蓋了從尋找保護替代物到證明功效的一切。

What is it going to take here?

這裡要做什麼？

I don't think anybody knows.

我想沒有人知道。

I think all options are currently open, but it's a rapidly evolving field.

我認為目前所有選擇都是開放的，但這是一個快速發展的領域。

And you can imagine that there actually is not yet a surrogate of protection because this is a very new virus, and people are still working to develop those assays and models.

你可以想像，實際上還沒有替代的保護措施，因為這是一種非常新的病毒，人們仍在努力開發這些檢測方法和模型。

I would give NIH a lot of credit for being at the forefront of that effort, and we're closely collaborating with them on these efforts.

我對 NIH 處於這一努力的前沿表示高度讚揚，並且我們正在與他們在這些努力上密切合作。

As it relates to the vaccination paradigm for CMV, I think the starting point here is clearly going to be in women of childbearing age.

由於它與 CMV 疫苗接種範式相關，我認為這裡的起點顯然是育齡婦女。

That's where you would anticipate the greatest benefit.

這就是您期望獲得最大收益的地方。

And I think the next phase is going to be to get into a GARDASIL-like population of adolescents because, obviously, you want to start protection as early as possible, given that's what -- the disease we're trying to prevent here is obviously going to be in infants born to women.

我認為下一階段將是進入類似 GARDASIL 的青少年群體，因為顯然，你希望儘早開始保護，因為我們在這裡試圖預防的疾病顯然是將發生在女性所生的嬰兒中。

So we're going to try and get down to that age group as we develop this vaccine.

因此，在開發這種疫苗時，我們將嘗試著眼於該年齡段。

Our next question is from Salveen Richter of Goldman Sachs.

我們的下一個問題來自高盛的 Salveen Richter。

It's Ross on for Salveen.

羅斯替補薩爾文。

Just a few here from me.

我這裡只有一些。

So just quickly on coronavirus.

所以，盡快應對冠狀病毒。

What's the potential monetary opportunity here?

這裡潛在的貨幣機會是什麼？

Do you guys have any details around agreements with the NIH about funding to you guys?

你們有關於與 NIH 就向你們提供資金的協議的任何細節嗎？

So just thinking about the monetary opportunity there to Moderna.

因此，只要考慮一下 Moderna 的貨幣機會即可。

And then on the Chikungunya antibody program, how much follow-up time exists since like the initial patient was first dosed and then since he was -- since he received a second dose?

然後，在基孔肯雅病毒抗體計劃中，從最初的患者第一次接受劑量開始，到他接受第二次劑量開始，還有多長時間的隨訪時間？

And are you guys seeing any signs of like innate immune response?

你們是否看到任何類似先天免疫反應的跡象？

And then I have a follow-up.

然後我有一個後續行動。

Good.

好的。

So it's Stéphane.

所以這是斯蒂芬。

I'm going to start with the first one.

我將從第一個開始。

On corona, our only focus as a team is public health.

對於新冠病毒，我們作為一個團隊唯一關注的焦點是公共衛生。

People are sick all over the planet.

全世界的人都生病了。

People are dying.

人們正在死去。

But this is our only focus, is to get a vaccine as fast as we can safely, partnering with the right people to get it done.

但這是我們唯一的重點，就是盡快安全地獲得疫苗，並與合適的人合作來完成這項工作。

Let me answer.

讓我來回答一下。

If I understood correctly your question on the Chikungunya monoclonal antibody.

如果我理解正確你關於基孔肯雅單克隆抗體的問題。

These data are emerging.

這些數據正在不斷湧現。

We're giving you an execution update on to-- in terms of where we are.

我們正在向您提供有關我們目前狀況的最新執行情況。

Once I have a full sense of the data set there, I'll of course update everybody.

一旦我全面了解了那裡的數據集，我當然會向大家通報最新情況。

Great.

偉大的。

And then just lastly, so outside of the Phase II CMV update in 3Q, what programs are you expecting to have data this year?

最後，除了第三季度的第二階段 CMV 更新之外，您預計今年會有哪些項目獲得數據？

We -- as you know, we don't guide to a specific timing on various milestones.

如您所知，我們不會指導各種里程碑的具體時間。

I'd refer back to the slide which had the rich catalyst calendar and clinical data calendar that we referred to.

我會回顧一下幻燈片，其中包含我們提到的豐富的催化劑日曆和臨床數據日曆。

That list of events that included data readouts as well as advancement of programs is -- it's a list that comprises all the next steps.

包括數據讀出和程序進展的事件列表是——它是一個包含所有後續步驟的列表。

Some of those have advanced fairly far along.

其中一些已經取得了相當大的進展。

For instance, I would note that the Phase I vaccine studies for RSV and Zika have been running since last year.

例如，我要指出的是，RSV 和 Zika 疫苗的第一階段研究自去年以來一直在進行。

And other instances, you'll recall that, as you pointed out, the Chikungunya antibody program is -- it's a relatively small study in healthy volunteers.

在其他情況下，您會記得，正如您所指出的，基孔肯雅病毒抗體計劃是——這是一項針對健康志願者的相對較小的研究。

But again, we're focused on advancing all these programs as rapidly as we can towards data.

但我們再次強調，我們的重點是盡快推進所有這些項目的數據化。

Next question is from Geoff Meacham of Bank of America.

下一個問題來自美國銀行的傑夫·米查姆。

This is Alec on for Geoff.

這是亞歷克（Alec）替傑夫（Geoff）發言。

Two questions from me.

我有兩個問題。

My first is on your PCV program, and I guess, the KRAS vaccine as well, have you guys seen any updated data from these studies, including the ongoing Phase I for the PCV since ASCO?

我的第一個是關於你們的 PCV 計劃，我想還有 KRAS 疫苗，你們有沒有看到這些研究的任何更新數據，包括自 ASCO 以來正在進行的 PCV 第一階段？

Just trying to get a sense of why this modality hasn't made the cut for your core franchises given it's one of the more advanced in terms of clinical development.

只是想了解為什麼這種模式沒有成為您的核心特許經營權，因為它是臨床開發方面更先進的模式之一。

And then I've got one more.

然後我還有一個。

Thanks, Alec.

謝謝，亞歷克。

It's Tal.

是塔爾。

Look, on the planned cancer vaccine.

看看，計劃中的癌症疫苗。

It's a Phase I, so data continues to come in.

這是第一階段，因此數據不斷湧入。

Once we have a full cogent data set there, we will be disclosing it.

一旦我們有了完整的、有說服力的數據集，我們就會將其公開。

The question of why we don't consider this a core, I think, for us, core is one that we have gotten the requisite pharmacology to believe it will translate into a clinical benefit.

為什麼我們不認為這是一個核心的問題，我認為，對我們來說，核心是我們已經獲得了必要的藥理學相信它將轉化為臨床益處的核心。

And I think that's true both for the vaccines, clearly.

我認為對於疫苗來說顯然也是如此。

And it's also true for the secreted and the surface protein expression because the Chikungunya monoclonal antibody actually reached what would otherwise be therapeutic levels of a protein.

對於分泌蛋白和表面蛋白表達來說也是如此，因為基孔肯雅單克隆抗體實際上達到了蛋白的治療水平。

So that's why it's core.

這就是為什麼它是核心。

I think in oncology, until you actually show that you're -- the pharmacology that you're describing, in this case, immunology, and T cell immunology, until you actually demonstrate that, that translates into a clinical benefit for patients, it's hard for me to call it core.

我認為在腫瘤學領域，直到你真正證明你所描述的藥理學，在這種情況下，免疫學和 T 細胞免疫學，直到你真正證明這一點，轉化為對患者的臨床益處，它是我很難稱之為核心。

Got it.

知道了。

That's very helpful.

這非常有幫助。

And then secondly, do you have any updates on the CF partnership with Vertex?

其次，您有關於 CF 與 Vertex 合作的任何更新嗎？

We've seen Vertex partner with some other gene therapy approaches from CRISPR Therapeutics, Semma and others.

我們已經看到 Vertex 與 CRISPR Therapeutics、Semma 等公司的其他一些基因治療方法合作。

So any color you can give on this partnership would be great.

因此，您可以為這種夥伴關係賦予任何色彩都很棒。

Yes.

是的。

We don't generally comment on research.

我們一般不會對研究發表評論。

So we continue to work with Vertex.

因此我們繼續與 Vertex 合作。

We're pleased to be working with them in the CFTR space, but we don't have any updates at this time.

我們很高興在 CFTR 領域與他們合作，但目前我們沒有任何更新。

Our next question is from 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 of them for you.

其中兩個給你。

First is another one on coronavirus, just thinking a little bit further out.

第一個是關于冠狀病毒的另一個，只是想得更遠一些。

Just curious, what kind of manufacturing capacity you anticipate having, say, looking out to 2021 even?

只是好奇，您預計 2021 年將擁有什麼樣的製造能力？

Should you need to manufacture mRNA-1273 for coronavirus?

您是否需要生產冠狀病毒的 mRNA-1273？

And then secondly, for the CMV program, I mean, if you could just kind of broadly talk about what a win would look like in that interim update for the Phase II we'll get in 3Q?

其次，對於 CMV 計劃，我的意思是，您是否可以廣泛地談論我們將在第三季度獲得的第二階段臨時更新中的勝利是什麼樣子？

Is this more or less kind of just looking to replicate the Phase I results on a larger group of patients?

這或多或少只是想在更多的患者群體中復制第一階段的結果？

Or are there nuances we should be thinking about?

還是我們應該考慮一些細微差別？

So Cory, it's Stéphane.

科里，這是斯蒂芬。

So I'll take the first one on manufacturing capacity.

所以我將討論第一個關於製造能力的問題。

I think the punchline is just too early to know precisely.

我認為現在要準確地了解這一點還為時過早。

Plus, we don't know the dose, when fill, finish with Norwood CMO capacity -- potentially new sites.

另外，我們不知道諾伍德 CMO 產能（可能是新地點）填滿後的劑量。

So just way too early to comment on that.

所以對此發表評論還為時過早。

But we are working hard to get as much as we can.

但我們正在努力爭取盡可能多的成果。

Cory, It's Tal.

科里，我是塔爾。

Let me answer your question on CMV Phase II.

讓我回答你關於 CMV II 期的問題。

So I think in a nutshell, the goal here is, as you say, to replicate what we saw in the Phase I. But I'd like to be able to do that, of course, in a larger data set, so that our confidence in picking the right dose for Phase III is there.

所以我認為簡而言之，正如你所說，這裡的目標是複制我們在第一階段看到的內容。但我當然希望能夠在更大的數據集中做到這一點，以便我們的我們有信心為III 期選擇正確的劑量。

And that has to do both with replicating the nice immunogenicity that we've seen, but being able to kind of plant a clear flag on what we expect in terms of the safety and tolerability profile that would enable us to go into a Phase III trial.

這既與復制我們所看到的良好免疫原性有關，又與我們在安全性和耐受性方面的期望樹立一個明確的標誌，這將使我們能夠進入 III 期試驗。

Our next one is from Hartaj Singh of Oppenheimer & Company.

我們的下一篇文章來自 Oppenheimer & Company 的 Hartaj Singh。

I have just a question on CMV.

我有一個關於 CMV 的問題。

With the Phase II results coming up in the third quarter and then the Phase III getting going, could you talk a little bit about how you could speed it to market?

隨著第二階段的結果在第三季度公佈，然後第三階段開始進行，您能談談如何加快其上市速度嗎？

I know that's -- a lot will be dependent on the Phase II results, but can you give us some sort of a kind of a confidence of more or less to when you think the Phase III could read out and by which time it could be on the market, 2024, '25, '26?

我知道這在很大程度上取決於第二階段的結果，但是您能給我們某種程度的信心嗎？您認為第三階段何時可以讀出以及什麼時候可以讀出在市場上，2024 年，'25，'26？

And then just a follow-on to that, which is that you've quoted the CMV opportunity as being $2 billion to $5 billion, which seems to make a lot of sense because as you get to broader and broader immunity.

接下來就是你引用的 CMV 機會為 20 億至 50 億美元，這似乎很有意義，因為當你獲得越來越廣泛的免疫力時。

Can you just broadly walk us through what kind of patient populations would you want to sort of have the vaccine broaden into to get to that higher point of that range?

您能否大致向我們介紹一下您希望將疫苗擴大到哪些類型的患者人群，以達到該範圍的更高點？

Hartaj, this is Tal.

哈塔傑，這是塔爾。

Let me start by answering the first question.

讓我首先回答第一個問題。

So look, the time line for CMV, roughly speaking, once we get in, we anticipate fairly aggressively to be able to complete enrollment within 18 months.

所以看，CMV 的時間線，粗略地說，一旦我們進入，我們預計能夠在 18 個月內完成註冊。

I anticipate the duration of the trial to be 2 years.

我預計審判時間為兩年。

Now that still needs, of course, vetting with regulatory authorities.

當然，現在仍然需要監管機構的審查。

So I want to make sure I caveat that appropriately.

所以我想確保我適當地警告了這一點。

Once that we have 2 years on everybody on study, then it's a matter of analyzing, looking at the results and filing, and that's where I think the time lines are pretty well understood for what's achievable in our industry.

一旦我們每個人都有兩年的時間進行研究，接下來就是分析、查看結果和歸檔的問題，這就是我認為我們行業可以實現的目標的時間線已經很好理解的地方。

So you can do the math from there.

所以你可以從那裡進行數學計算。

Yes.

是的。

And Stéphane, I'll take the second one on CMV, what it will take to get to $5 billion type of number.

Stéphane，我將談第二個關於 CMV 的問題，即如何才能達到 50 億美元的數字。

I think a few things.

我想有幾件事。

The first one is, as we explained at the R&D Day in September, it will take definitely an indication approval in women in childbearing age, which, as you know, is our first one; then to get into adolescent approval, like the HPV GARDASIL; and third is to get to pediatric.

第一個是，正如我們在九月份的研發日所解釋的那樣，它肯定需要在育齡婦女中獲得適應症批准，正如你所知，這是我們的第一個；然後獲得青少年的認可，例如 HPV GARDASIL；第三是兒科。

As we shared, humans are the reservoir for CMV.

正如我們所分享的，人類是 CMV 的宿主。

We believe it's a very important public health opportunity here to vaccinate newborns in the pediatric setting.

我們認為，在兒科環境中為新生兒接種疫苗是一個非常重要的公共衛生機會。

That has been done, as you know, successfully with Rubella, to eradicate the virus, and to make sure that humans don't get infected by these virus, which has a lot of long-term negative impact on health, both at the population as well as for individuals and their own immune system and their own health.

如您所知，我們已經成功地消滅了風疹病毒，並確保人類不會被這些病毒感染，這對人群的健康產生了很多長期的負面影響以及個人及其自身的免疫系統和自身的健康。

Another dimension, of course, is competitive landscape.

當然，另一個維度是競爭格局。

Are we going to be the only one on the market for next 10 years or are we going to be with 1 competitor, or 2 competitor or 5 competitors.

我們是否會成為未來 10 年市場上唯一的競爭者，還是會與 1 個競爭對手、2 個競爭對手或 5 個競爭對手並存？

I can come back on that if you adjust it moving further.

如果你進一步調整它，我可以回來討論這一點。

And then it's population growth.

然後是人口增長。

There's a lot of emerging markets that are not only growing in size in our population growth, but also in term of dollar invested per inhabitant.

許多新興市場的規模不僅在人口增長方面不斷擴大，而且在人均投資美元方面也在不斷增長。

If you think about the 5-year, 10-year, 15-year time frame.

如果你考慮5年、10年、15年的時間框架。

That will impact the model that we have for getting to around $5 billion in our annual peak sales.

這將影響我們實現年度峰值銷售額約 50 億美元的模式。

Our next question is from Yasmeen Rahimi of Roth Capital Partner.

我們的下一個問題來自 Roth Capital Partners 的 Yasmeen Rahimi。

Thank you for the tremendous progress that you're making quarter-over-quarter.

感謝您每個季度取得的巨大進步。

A few questions for you all related on CMV.

有幾個關於 CMV 的問題要問大家。

The first one is, can you give us a little bit more color on how we think about how current the numbers are in regards to infection rates?

第一個問題是，您能否進一步說明我們如何看待感染率方面的最新數字？

If there are differences between U.S. and Europe.

如果美國和歐洲之間存在差異。

How current they are as it guides you sort of for powering assumptions in your Phase III?

它們的最新程度如何，因為它可以指導您為第三階段的假設提供動力？

And then a second question that we often get is, as you're in a phenomenal part of being able to scale up, and we're going to learn more in manufacturing on March 4. Can you enlighten us what are aspects that are unique when you're scaling up an mRNA therapeutic versus other RNA modalities?

然後我們經常遇到的第二個問題是，由於您正處於能夠擴大規模的驚人階段，我們將在 3 月 4 日了解更多製造方面的信息。您能否告訴我們哪些方面是獨特的當您與其他RNA 療法相比擴大mRNA 療法的規模時？

Just so we have a little bit of color, and nuances that you are looking here.

只是為了讓我們有一些你在這裡看到的顏色和細微差別。

All right.

好的。

It's me.

這就是我。

It's Tal.

是塔爾。

Let me take your first question.

讓我回答你的第一個問題。

It's a great question and it's one that obviously keeps me up at night.

這是一個很好的問題，顯然也是一個讓我徹夜難眠的問題。

I think the literature is out there in terms of incidence rates and infections.

我認為關於發病率和感染情況的文獻是存在的。

But it's also clear from that literature that there's a high level of variability.

但從該文獻中也可以清楚地看出，存在很大的可變性。

And it's not just on a continental level, U.S. versus Europe, but it's actually local geographies, socioeconomic status, a lot of things that play into that.

這不僅僅是在大陸層面上，美國與歐洲，而且實際上是當地的地理位置、社會經濟地位，以及很多因素的影響。

So how are we thinking about it in terms of designing the trial, which is, obviously, I think where your question is going to.

那麼，我們如何在設計試驗方面考慮這個問題，顯然，我認為你的問題將在哪裡。

I think the goal here is to design both a large trial and a broad enough trial in terms of sites and populations.

我認為這裡的目標是設計一個大型試驗，並且在地點和人群方面設計一個足夠廣泛的試驗。

So that on average, we are able to hit the incidence rate that people have described.

因此，平均而言，我們能夠達到人們描述的發病率。

And I'm pretty confident in the ballpark of where we are powering the study to be able to reach it.

我對我們為這項研究提供支持以實現這一目標的大致範圍充滿信心。

And finally, I would note that in a trial of this type, you have the ability to actually, on an ongoing basis, monitor the incidents in real time.

最後，我要指出的是，在此類試驗中，您實際上有能力持續實時監控事件。

So that the only risk you're really taking, if you're missing it, is you follow subjects for longer and you catch up the cases.

因此，如果你錯過了它，你真正承擔的唯一風險就是你更長時間地跟踪主題並趕上案例。

So it'll -- ultimately, the trial size will come down to the number of cases.

因此，最終審判規模將取決於案件數量。

And that's one that you can monitor in almost real time.

您幾乎可以實時監控這一情況。

So Yasmeen, it's Stéphane.

亞斯明，我是斯蒂芬。

On the manufacturing process and why mRNA is such a powerful molecule.

關於製造過程以及 mRNA 為何如此強大的分子。

I think a few things.

我想有幾件事。

I mean the first thing is it's a liquid-based process to make mRNA, which is cell-free so that drives to a very small reactors compared to other technologies, especially if you compare to recombinant it's the most staggering changes, can too for given our -- just the size of our reactors, which, of course, has a big impact on your CapEx, including all your purification technologies because you just have less liters to go through the (inaudible).

我的意思是，第一件事是它是一種基於液體的製造mRNA 的過程，它是無細胞的，因此與其他技術相比，它需要一個非常小的反應器，特別是如果你與重組技術相比，它是最驚人的變化，對於給定的情況也可以我們的——只是我們反應器的大小，當然，這對您的資本支出有很大影響，包括您所有的淨化技術，因為您需要通過的升數更少（聽不清）。

So everything is much, much cheaper across the board.

因此，一切都非常非常便宜。

As we talked in the past, because mRNA is an information molecule, it is the same process for Zika, or for CMV, or for coronavirus.

正如我們過去談到的，因為 mRNA 是一種信息分子，所以對於寨卡病毒、CMV 或冠狀病毒來說，它都是相同的過程。

So drives incredible flexibility and the incredible time to the clinic, because do not have to invent the process for every vaccine or every molecule, as the team has shown in the last few weeks with coronavirus.

因此，這帶來了令人難以置信的靈活性和令人難以置信的臨床時間，因為不必為每種疫苗或每種分子發明流程，正如該團隊在過去幾週針對冠狀病毒所展示的那樣。

If we have had like traditional technologies to invent a new process just for corona, we'd still be working at it as we speak.

如果我們像傳統技術那樣發明一種專門針對新冠病毒的新工藝，那麼在我們說話的時候我們仍然會致力於它。

And we most probably not even have started to make the product.

我們很可能還沒有開始生產該產品。

In our case, we're able to just do a tiny bit of [optimization] for the very large molecule that this mRNA is and then go right into production.

在我們的例子中，我們只需對該 mRNA 的非常大的分子進行一點點[優化]，然後就可以直接投入生產。

Thanks to the -- this aspect of a platform that we have.

感謝我們所擁有的平台的這一方面。

And definitely it is time which is -- the cycle time to make mRNA is days, not weeks.

毫無疑問，這就是時間——製造 mRNA 的周期時間是幾天，而不是幾週。

And so when you think about that, you can use an asset.

因此，當您考慮到這一點時，您可以使用資產。

I mean once you make one lot, you can basically change the disposable equipment and use the same room or the same team to make another product.

我的意思是，一旦你生產了一批產品，你基本上就可以更換一次性設備，並使用同一個房間或同一個團隊來生產另一種產品。

And so if you can deliver few days to make mRNA versus a few weeks to make a recombinant before you're going to go into fill, finish, that's a massive use of your capital infrastructure in term of just CapEx turnover.

因此，如果您可以在進入填充、完成之前交付幾天的時間來製造mRNA，而不是幾週的時間來製造重組體，那麼就資本支出周轉率而言，這就是對您的資本基礎設施的大量利用。

(Operator Instructions) And next one is from Alan Carr of Needham.

（操作員說明）下一篇來自 Needham 的 Alan Carr。

And a couple of them.

還有其中的幾個。

One of them is can you clarify between your exploratory and your core modalities?

其中之一是你能澄清你的探索模式和核心模式嗎？

Does this mean that you don't plan to add any more new programs to your exploratory until they become core?

這是否意味著您不打算在您的探索中添加更多新程序，直到它們成為核心？

And then also around RSV, 1345 versus 1172.

然後也是圍繞 RSV，1345 與 1172。

How are they different?

它們有何不同？

And how does this fall outside of the agreement that you already have with Merck around RSV?

這怎麼會超出你們與默克公司就 RSV 達成的協議呢？

And the last thing is can you go over the -- your overall manufacturing capacity at the Norwood facility right now across all programs, the total capacity?

最後一件事是，您能否回顧一下諾伍德工廠目前所有項目的總體製造能力，即總產能？

And without regard to coronavirus, what were your -- what are your long-term plans in terms of your needs for capacity in terms of adding manufacturing capacity in the long term as you go commercial?

不考慮冠狀病毒，您的長期計劃是什麼？就您在商業化過程中長期增加製造能力方面的產能需求而言，您的長期計劃是什麼？

Good.

好的。

Thanks for those 3 questions.

謝謝你提出這3個問題。

So let me take the first one on exploratory and core.

那麼，讓我來談談第一個關於探索性和核心性的問題。

So yes, if you go back to the strategy, we started with 6 modalities in the clinic to say we cannot manage the unknown, unknown.

所以，是的，如果你回到策略上來，我們從診所的 6 種模式開始，說我們無法管理未知的事物。

And so because of the exciting opportunity to create a new class of medicine, we are very focused on managing the unknown technology risk.

因此，由於創造新型藥物的令人興奮的機會，我們非常專注於管理未知的技術風險。

And so we tried of those 6 technology in parallel, so we could learn from the clinic where to invest more because mRNA is an information molecule making it to platform, and wherever you wanted to fix.

因此，我們並行嘗試了這 6 種技術，這樣我們就可以從診所了解在哪裡進行更多投資，因為 mRNA 是一種信息分子，可以將其帶到平台上，以及您想要修復的任何地方。

If you learn something about the science, fix that science if you can or decide that you are stop investing in that opportunity, you want to deploy your capital wisely where you know the technology is working.

如果您了解了一些有關科學的知識，並且可以修復該科學，或者決定停止投資該機會，那麼您希望在您知道該技術正在發揮作用的地方明智地部署您的資本。

So that was kind of a premise as we started.

所以這是我們開始時的一個前提。

And so what is happening with this pivot in the company history is that now we have a clinical data we gathered for prophylactic vaccine and systemic therapeutics.

因此，公司歷史上這一關鍵點所發生的事情是，現在我們擁有了為預防性疫苗和全身治療收集的臨床數據。

We believe those are core, i.e., in our opinion, we believe the technology risk is off the table, meaning we want to deploy our capital to make innovative medicine that goes to the clinic, because it's exactly the same technology, same manufacturing process than the ones we already have the positive clinical data.

我們相信這些是核心，也就是說，我們認為，技術風險是不存在的，這意味著我們希望利用我們的資本來製造進入臨床的創新藥物，因為它與傳統藥物完全相同的技術、相同的製造工藝。我們已經擁有積極的臨床數據。

On the exploratory front, yes, we want to be very cautious, and that has been the case for years.

在探索方面，是的，我們要非常謹慎，多年來一直如此。

We say doing only one program per exploratory modality seems too risky for us because you have biology risk and there's always biology risk.

我們說，每種探索方式只做一個項目對我們來說似乎風險太大，因為你有生物學風險，而且總是存在生物學風險。

But we always say a few -- 2, 3 programs kind of make sense for us, as what you see.

但我們總是說一些——2、3 個程序對我們來說是有意義的，正如你所看到的。

So do we intend to invest more shareholder capital on more [infrastructure], more -- for example -- an example of 1 of the 4 exploratory right now?

那麼，我們是否打算將更多的股東資本投資於更多的[基礎設施]，更多——例如——現在4個探索性項目中的1個的例子？

The answer is clearly no.

答案顯然是否定的。

We want to see what we get from OX40, IL-12 and the triplet.

我們想看看從 OX40、IL-12 和三聯體中得到什麼。

But like we've done with those 2 modalities that have migrated from exploratory to core in the last few months, if we get signal, the team has a lot of ideas of what other things we could do.

但就像我們在過去幾個月裡對這兩種模式所做的那樣，它們從探索性轉向了核心，如果我們收到信號，團隊就會對我們可以做的其他事情有很多想法。

And of course, then those programs where we get positive readout, we'll take those as fast as we can to BLA because those medicine will be needed for patients.

當然，對於那些我們得到積極結果的項目，我們會盡快將其帶到 BLA，因為患者將需要這些藥物。

Stephen, you want to talk about RSV?

斯蒂芬，你想談談 RSV 嗎？

Yes, just quickly on RSV.

是的，只需快速查看 RSV。

So Alan, as you referenced, we have a partnership with Merck in respiratory syncytial virus, just a monotherapy vaccine.

所以艾倫，正如你提到的，我們與默克在呼吸道合胞病毒方面有合作夥伴關係，只是一種單一療法疫苗。

There are 2 candidates in Phase I study.

第一階段研究中有 2 名候選人。

V172 is the one that is currently being conducted.

V172 是目前正在進行的一項。

And those are targeting the elderly target product profile.

這些都是針對老年人的目標產品概況。

And so there is a nearly equal burden of disease in the elderly, 170,000 hospitalizations a year in this country.

因此，老年人的疾病負擔幾乎相同，在這個國家每年有 170,000 人住院。

We're excited to be working with Merck in that elderly population.

我們很高興能與默克在老年人群中合作。

We have a right in our agreement, as we disclosed, to conduct development of an RSV vaccines towards a respiratory combination, and that had been our intent.

正如我們所披露的，我們在協議中有權開發針對呼吸道組合的 RSV 疫苗，這也是我們的意圖。

And so we are -- that is separate from Merck's prerogatives in RSV.

所以我們是——這與默克在 RSV 方面的特權是分開的。

Good.

好的。

Thanks, Stephen.

謝謝，斯蒂芬。

And on the last question, on manufacturing capacity.

關於最後一個問題，關於製造能力。

So maybe let me try to tease it out -- a pre-coronavirus world, which we talked about in previous calls and previous discussion, which is our manufacturing long-term plan is to use Norwood to make development material like we are doing today and to launch our commercial products like CMV, Zika and the others out of Norwood, because of how Norwood was designed.

所以也許讓我試著梳理一下——冠狀病毒爆發前的世界，我們在之前的電話和討論中談到過，這是我們製造業的長期計劃是使用諾伍德來製造開發材料，就像我們今天所做的那樣，由於諾伍德的設計方式，我們在諾伍德推出了 CMV、Zika 等商業產品。

We've always said to manage financing risk, we do not want to invest in a big manufacturing capacity commercial plant until we are, of course, BLA approved, purely risk management.

我們總是說，為了管理融資風險，我們不想投資大型製造能力的商業工廠，當然，除非我們獲得 BLA 批准，純粹是風險管理。

But we've always said our long-term vision is to have Norwood focus on development, so that we have a commercial site and hopefully down the road as we scale the company several around the planet that are just focused on commercial products.

但我們一直說，我們的長期願景是讓諾伍德專注於開發，以便我們擁有一個商業網站，並希望隨著我們在全球範圍內擴大公司規模，專注於商業產品。

We believe, based on our experience in previous pharmaceutical companies, that having dedicated focus per site is really important for success.

我們相信，根據我們在之前製藥公司的經驗，每個站點的專注對於成功非常重要。

Development requires nimbleness.

發展需要敏捷。

Commercial requires scale and efficiencies.

商業需要規模和效率。

Very different worlds.

非常不同的世界。

So that's kind of a pre-coronavirus world, our previous plans.

這就是我們之前的計劃，即冠狀病毒爆發前的世界。

And the post coronavirus, while in the last few weeks, I go back to my previous answer a few minutes ago, which is we are looking at a lot of options, both internally, externally, CMO partners, to figure out what's the right path forward.

在冠狀病毒之後，在過去的幾周里，我回到了幾分鐘前的回答，即我們正在考慮很多選擇，包括內部、外部、CMO 合作夥伴，以找出正確的道路向前。

And when we have a better picture, we will share it.

當我們有更好的圖片時，我們會分享它。

Thank you.

謝謝。

That ends our Q&A session.

我們的問答環節到此結束。

I would now like to hand the call back to Stéphane Bancel.

現在我想將電話轉回給 Stéphane Bancel。

Well, thank you for your question.

嗯，謝謝你的提問。

Especially, thank you for your trust into our ability to make mRNA an important new class of medicines.

特別感謝您對我們使 mRNA 成為重要的新型藥物的能力的信任。

We hope to see many of you next week in Norwood for what I believe will be an exciting Manufacturing and Digital Day.

我們希望下週在諾伍德見到你們，我相信這將是令人興奮的製造和數字日。

Thank you.

謝謝。

Thank you.

謝謝。

This concludes today's conference call.

今天的電話會議到此結束。

Thank you all for attending.

感謝大家的出席。

You may now disconnect.

您現在可以斷開連接。