莫德納 (MRNA) 2019 Q2 法說會逐字稿

Good morning, and welcome to Moderna's Second Quarter 2019 Conference Call.

早上好，歡迎參加 Moderna 2019 年第二季度電話會議。

(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.

此時，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, and welcome to Moderna's second quarter 2019 conference call to discuss business update and financial results.

早上好，歡迎參加 Moderna 2019 年第二季度電話會議，討論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 at www.modernatx.com.

您可以訪問我們網站 www.modernatx.com 的投資者部分，查看今天上午發布的新聞稿以及我們將審閱的幻燈片。

Today, on this call, we have Stéphane Bancel, our Chief Executive Officer; Stephen Hoge, our President; Tal Zaks, our Chief Medical Officer; and Lorence Kim, our Chief Financial Officer.

今天，我們的首席執行官 Stéphane Bancel 出席了這次電話會議；斯蒂芬·霍格，我們的總裁； Tal Zaks，我們的首席醫療官；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, and good morning, everyone.

謝謝拉維娜，大家早上好。

We believe that mRNA has the potential to be a new class of medicines.

我們相信 mRNA 有潛力成為一類新的藥物。

We believe our mRNA medicines have the potential to address large unmet medical needs and to treat diseases that are not addressable by recombinant proteins or small molecules.

我們相信我們的 mRNA 藥物有潛力解決大量未滿足的醫療需求，並治療重組蛋白或小分子無法解決的疾病。

Due to the platform nature of mRNA, we believe our mRNA medicines provide a higher probability of technical success and faster timelines to clinical trials and to the market relative to traditional medicines.

由於 mRNA 的平台性質，我們相信相對於傳統藥物，我們的 mRNA 藥物能夠提供更高的技術成功概率以及更快的臨床試驗和市場時間表。

We also believe that the manufacturing capital intensity of mRNA is materially lower than recombinant protein and that our manufacturing cost at commercial scale will be similar to small molecule injectable.

我們還相信，mRNA 的製造資本強度大大低於重組蛋白，並且我們在商業規模上的製造成本將與小分子注射劑相似。

Because of this large potential, we continue to focus on managing the risk across our portfolio, especially technology risk and biology risk.

由於這種巨大的潛力，我們繼續專注於管理整個投資組合的風險，特別是技術風險和生物風險。

We believe that programs within the same modality have similar technology risk, meaning that once we derisk a sentinel program, they are important breakthroughs.

我們認為，相同模式下的項目具有相似的技術風險，這意味著一旦我們消除哨兵項目的風險，它們就是重要的突破。

As a key, therefore, in the near future, we believe our chikungunya antibody program will be an important clinical readout as it uses the same formulation technology as our MMA program, our most advanced rare disease candidate.

因此，作為關鍵，在不久的將來，我們相信我們的基孔肯雅抗體項目將成為重要的臨床讀數，因為它使用與我們最先進的罕見疾病候選藥物 MMA 項目相同的配方技術。

Our corporate focus is on 3 priorities: first, to execute on the development pipeline; two, to move new development candidate in existing modalities from the lab into the clinic; and three, to invest new development candidates in new modalities.

我們公司的重點是三個優先事項：第一，執行開發流程；第二，將現有模式中的新開發候選藥物從實驗室轉移到臨床；第三，以新模式投資新的發展候選者。

I will review now our most important progress since our last quarterly update in early May.

我現在將回顧自五月初上一次季度更新以來我們最重要的進展。

Starting with PCV, personalized cancer vaccine.

從 PCV 開始，個性化癌症疫苗。

We projected positive interim Phase I data at the ASCO meeting in June and since, we are happy to report today that since ASCO, we started a Phase II head-to-head trial in the adjuvant melanoma setting.

我們在 6 月份的 ASCO 會議上預測了積極的中期 I 期數據，自此，我們今天很高興地報告，自 ASCO 以來，我們在輔助黑色素瘤環境中開始了 II 期頭對頭試驗。

We look forward to the readout of this important immuno-oncology program to assess if PCV plus Merck's KEYTRUDA can increase recurrence-free survival versus KEYTRUDA monotherapy.

我們期待公佈這一重要的免疫腫瘤學計劃，以評估 PCV 聯合默克公司的 KEYTRUDA 與 KEYTRUDA 單一療法相比是否可以提高無復發生存率。

We are happy to report today that the Phase I for CMV has completed and in all healthy subject at doses up to 300 microgram.

今天我們很高興地報告，CMV 的第一階段已經完成，並且在所有健康受試者中的劑量高達 300 微克。

We believe CMV is a large unmet medical need, and we look forward to reviewing and showing the Phase I trial data in the near term.

我們相信 CMV 是一個巨大的未滿足的醫療需求，我們期待在短期內審查和展示 I 期試驗數據。

The team continued to execute at a rapid pace in the last 90 days.

在過去 90 天裡，團隊繼續快速執行。

We advanced 4 new programs into Phase I since our May quarter.

自 5 月份季度以來，我們將 4 個新項目推進到第一階段。

Two programs in immuno-oncology started dosing cancer patients.

免疫腫瘤學的兩個項目開始對癌症患者進行給藥。

Our KRAS vaccine, which is partnered with Merck, and the IL12 intratumor, which is partnered with AstraZeneca [dosed the first patients].

我們與默克 (Merck) 合作的 KRAS 疫苗以及與阿斯利康 (AstraZeneca) 合作的 IL12 瘤內疫苗 [已對第一批患者進行給藥]。

Two programs in infectious vaccine started dosing as well.

兩個傳染性疫苗項目也開始給藥。

Our RSV vaccine, mRNA-1172, partnered with Merck and our Zika vaccine, mRNA-1893, which is funded by the U.S. agency, BARDA.

我們的 RSV 疫苗 mRNA-1172 與默克 (Merck) 合作，我們的寨卡疫苗 mRNA-1893 由美國機構 BARDA 資助。

Finally, I am happy to report that clinical sites are now open and actively recruiting patients in our first rare disease program, MMA.

最後，我很高興地向大家報告，臨床中心現已開放，並正在積極招募患者參與我們的第一個罕見病項目 MMA。

We have 3 open sites in the U.S. And in the U.K., the clinical trial application, or CTA, was just opened by local authorities.

我們在美國有 3 個開放站點，在英國，地方當局剛剛開放了臨床試驗申請 (CTA)。

I am very pleased with the company's progress and I am very thankful for the team dedication to this execution.

我對公司的進步感到非常滿意，也非常感謝團隊為此執行的奉獻精神。

We now have 5 immuno-oncology programs in the clinic, including PCV in Phase II and OX40 soon entering Phase II.

我們現在有5個免疫腫瘤項目在臨床，包括處於二期的PCV和即將進入二期的OX40。

We have 5 important rare disease program and are still working out to dose the first MMA patient and to submit INDs for all our rare disease programs.

我們有 5 個重要的罕見病項目，並且仍在努力為第一位 MMA 患者給藥並為我們所有的罕見病項目提交 IND。

We have 4 vaccines in the clinic for major unmet medical needs; CMV, RSV, the hMPV+

我們在診所有4種疫苗，可滿足重大未滿足的醫療需求； CMV、RSV、hMPV+

PIV (sic) [hMPV+

PIV（原文如此）[hMPV+

PIV3] combo and Zika.

PIV3]組合和寨卡。

I want to remind you that there are no approved vaccines for any of these harmful pathogens that similarly affect thousands each year.

我想提醒您，目前還沒有針對這些每年影響數千人的有害病原體的批准疫苗。

We are very pleased to have completed enrollment in our CMV trial and we look forward to sharing the data with you soon.

我們很高興已完成 CMV 試驗的註冊，並期待盡快與您分享數據。

The company has never been as strong and we're all focused on continuing to execute and share our progress in the months to come.

公司從未如此強大，我們都專注於在未來幾個月繼續執行和分享我們的進展。

With this, let me turn to Tal to give you some more color on the development pipeline.

說到這裡，讓我請塔爾為您提供有關開發流程的更多信息。

Thank you, Stéphane.

謝謝你，斯特凡。

As you know, we're advancing our pipeline of medicines in 6 different modalities.

如您所知，我們正在以 6 種不同的方式推進我們的藥物研發線。

In the next few slides, I will highlight the progress we've made this quarter in each of these.

在接下來的幾張幻燈片中，我將重點介紹本季度我們在各個方面取得的進展。

So starting with prophylactic vaccines on Slide 13.

所以從幻燈片 13 上的預防性疫苗開始。

You will see we have 8 programs in this modality and we've made significant progress in the last quarter.

您會看到我們在這種模式下有 8 個項目，並且我們在上個季度取得了重大進展。

In total today, we have safety data from over 100 healthy volunteers who have participated in our Phase I study and we remain pleased with the emerging safety and tolerability profile of our vaccines.

今天，我們總共獲得了來自參與我們第一階段研究的 100 多名健康志願者的安全數據，我們對我們疫苗不斷出現的安全性和耐受性狀況感到滿意。

I'm happy to report that our CMV program with mRNA-1647 is now fully enrolled in the Phase I trial, and I'll go over this opportunity in greater detail in just a moment.

我很高興地向大家報告，我們的 mRNA-1647 CMV 項目現已完全進入 I 期試驗，稍後我將更詳細地討論這個機會。

The RSV Phase I study testing mRNA-1172 dosed its first subjects in this quarter and recall that at the last quarterly update we reported that our partner, Merck, had just filed the IND.

測試 mRNA-1172 的 RSV I 期研究在本季度對第一批受試者進行了給藥，回想一下，在上一季度更新中，我們報告說我們的合作夥伴默克剛剛提交了 IND。

Our Zika program with mRNA-1893 also had the IND filed and opened in the second quarter, and I'm happy to report that the first subjects on the Zika Phase I trial was also dosed.

我們的 mRNA-1893 寨卡項目也在第二季度提交並啟動了 IND，我很高興地報告，寨卡 I 期試驗的第一批受試者也已接受給藥。

In terms of emerging data, in hMPV+

就新興數據而言，hMPV+

PIV3, or mRNA-1653, we continue to see neutralization titers above baseline at the second interim look, 7 months after the last vaccination.

PIV3 或 mRNA-1653，在最後一次疫苗接種 7 個月後的第二次中期檢查中，我們繼續看到中和滴度高於基線。

For context, in January, we reported the 2-month immunogenicity data.

作為背景，我們在一月份報告了 2 個月的免疫原性數據。

We plan to present the full data from this Phase I study at IDWeek in the fall.

我們計劃於秋季在 IDWeek 上展示這一第一階段研究的完整數據。

We're also pleased with the feedback from FDA regarding the development plans for mRNA-1653 where we discuss the potential path forward to evaluate protection against both hMPV and PIV3 in a single Phase III study.

我們還對 FDA 關於 mRNA-1653 開發計劃的反饋感到滿意，我們討論了在一項 III 期研究中評估對 hMPV 和 PIV3 的保護作用的潛在途徑。

Consistent with these plans, we plan to enroll seropistive toddlers in our next trial.

根據這些計劃，我們計劃在下一次試驗中招募患有血清反應的幼兒。

Finally, the Phase I data for influenza vaccines against age 7 and age 10 were published in the Journal of Vaccine.

最後，針對7歲和10歲流感疫苗的I期數據發表在《疫苗雜誌》上。

Let me know spend a few minutes on CMV.

讓我知道花幾分鐘了解 CMV。

As noted, before the Phase I trial for CMV is fully enrolled, CMV is a common pathogen that is a leading cause of birth defects.

如前所述，在 CMV 的 I 期試驗完全招募之前，CMV 是一種常見病原體，是出生缺陷的主要原因。

The burden of disease is significant where approximately 25,000 newborns are infected each year in the U.S. alone.

疾病負擔非常嚴重，僅在美國每年就有大約 25,000 名新生兒受到感染。

Currently, there aren't any vaccines against the CMV virus on the market.

目前，市場上還沒有針對鉅細胞病毒病毒的疫苗。

That's because CMV is proving to be a challenging vaccine to manufacture using traditional technologies given the structure of one of the antigens, the pentamer, which we think is required to elicit a protective immune response.

這是因為，考慮到其中一種抗原五聚體的結構，CMV 被證明是一種使用傳統技術生產具有挑戰性的疫苗，我們認為這是引發保護性免疫反應所必需的。

We believe these challenges can be overcome with our mRNA vaccine as our technology lends itself to producing the pentameric viral antigen by encoding for the simultaneous translation of its 5 components.

我們相信我們的 mRNA 疫苗可以克服這些挑戰，因為我們的技術可以通過編碼其 5 個組件的同時翻譯來生產五聚體病毒抗原。

As a reminder, and as shown on Slide 15, mRNA-1647 actually contains 6 mRNA sequences, 5 of which encode for this pentamer and 1 that encodes for the gB protein.

提醒一下，如幻燈片 15 所示，mRNA-1647 實際上包含 6 個 mRNA 序列，其中 5 個編碼該五聚體，1 個編碼 gB 蛋白。

We believe the combination of these 2 antigens encoded by mRNA-1647 will produce potent and durable antibody titers against CMV that have the potential to protect against infection.

我們相信 mRNA-1647 編碼的這 2 種抗原的組合將產生有效且持久的抗 CMV 抗體滴度，具有預防感染的潛力。

We look forward to the Phase I results soon.

我們期待盡快獲得第一階段的結果。

Let me now turn to cancer vaccines.

現在讓我談談癌症疫苗。

You will see the programs in this modality on Slide 17, and I'll focus on mRNA-4157, our personalized cancer vaccine, and on the KRAS vaccine, mRNA-5671.

您將在幻燈片 17 上看到這種模式中的程序，我將重點介紹 mRNA-4157（我們的個性化癌症疫苗）和 KRAS 疫苗 mRNA-5671。

Recall that we and our partner, Merck, announced the Phase II trial earlier this year.

回想一下，我們和我們的合作夥伴默克公司今年早些時候宣布了第二階段試驗。

The Phase II design is a randomized trial testing the combination of mRNA-4157 in combination with pembrolizumab against the pembrolizumab monotherapy control arm in high-risk melanoma patients in the adjuvant setting.

II 期設計是一項隨機試驗，在高風險黑色素瘤患者中測試 mRNA-4157 聯合派姆單抗與派姆單抗單藥對照的組合，並進行輔助治療。

I'm happy to report today that the Phase II is up and running and that the first patients have consented to the trial.

我今天很高興地向大家報告，第二階段已經啟動並正在運行，並且第一批患者已同意試驗。

Interim safety tolerability and immunogenicity data from our Phase I were the basis for the decision to move to Phase II.

第一階段的臨時安全耐受性和免疫原性數據是我們決定進入第二階段的基礎。

We presented these interim data with mRNA-4157 either as monotherapy in a resected adjuvant population or in combination with pembrolizumab in the metastatic setting.

我們展示了 mRNA-4157 在切除輔助群體中作為單一療法或在轉移性環境中與派姆單抗聯合治療的這些中期數據。

These 2 arms represent arms A and arms B, respectively of the Phase I study.

這 2 個組分別代表 I 期研究的 A 組和 B 組。

We have a part C and part D that continue to enroll.

我們有 C 部分和 D 部分繼續招生。

Our [T] histologies include microsatellite stable, or MSS, colorectal cancer and head and neck squamous cell carcinoma.

我們的 [T] 組織學包括微衛星穩定 (MSS)、結直腸癌和頭頸鱗狀細胞癌。

We and our partner, Merck, have also added an additional cohort in part B where we will be testing the combination of mRNA-4157 with pembrolizumab in patients who are refractory to PD-1 inhibitors.

我們和我們的合作夥伴默克還在 B 部分中添加了一個額外的隊列，我們​​將在 PD-1 抑製劑難治性患者中測試 mRNA-4157 與派姆單抗的組合。

Turning now to the interim results we presented at ASCO of this year.

現在談談我們今年在 ASCO 上公佈的中期業績。

We've showed that mRNA-4157 was safe and well tolerated with no reported DLTs and no grade 3 or grade 4 adverse events.

我們已經證明 mRNA-4157 是安全的且耐受性良好，沒有報告 DLT，也沒有 3 級或 4 級不良事件。

We also show that mRNA-4157 elicited neoantigen-specific T cell activation in 10 of the 18 Class I neoantigens and the 1 patient treated at a top dose where apheresis was performed.

我們還表明，mRNA-4157 在18 種I 類新抗原中的10 種中引發了新抗原特異性T 細胞活化，並在1 名接受單採血液成分的最高劑量治療的患者中引發了新抗原特異性T 細胞活化。

While these data were obtained with the first version of our vaccine that included up to 20 neoantigens, we're now selecting for up to 34 neoantigens using our proprietary algorithm.

雖然這些數據是通過我們的第一版疫苗獲得的，其中包含多達 20 種新抗原，但我們現在使用我們的專有算法選擇多達 34 種新抗原。

For the data presented at ASCO, the patients were dosed with the PCV that had the 20 neoantigens and all patients who have enrolled since April in the both the Phase I and Phase II studies have been receiving the 34 neoantigen version.

對於 ASCO 上提供的數據，患者接受了含有 20 種新抗原的 PCV，自 4 月份以來參加 I 期和 II 期研究的所有患者都接受了 34 種新抗原版本。

At ASCO, while the clinical data are early and preliminary, we did report 6 responses in part B of the study in the metastatic setting.

在 ASCO，雖然臨床數據是早期和初步的，但我們確實在研究的 B 部分中報告了轉移性環境中的 6 個反應。

One of these was a complete responder to pembrolizumab monotherapy prior to receiving the personalized cancer vaccine and 5 other dosed with the combination of mRNA-4157 and pembrolizumab had a partial response.

其中一名患者在接受個性化癌症疫苗之前對派姆單抗單一療法有完全反應，另外 5 名接受 mRNA-4157 和派姆單抗聯合用藥的患者有部分緩解。

2 of these 5 PRs were patients who were previously treated with checkpoint inhibitors.

這 5 名 PR 中有 2 名是之前接受過檢查點抑製劑治療的患者。

While these early signals are trending in the right direction, we believe that our Phase II trial will help us and Merck to definitively ascertain the incremental benefit of mRNA-4157.

雖然這些早期信號正朝著正確的方向發展，但我們相信我們的 II 期試驗將幫助我們和默克最終確定 mRNA-4157 的增量益處。

Moving now to the KRAS vaccine.

現在轉向 KRAS 疫苗。

I'm also pleased to announce that the first patient in our Phase I trial testing KRAS vaccine mRNA-5671 was dosed.

我還很高興地宣布，我們測試 KRAS 疫苗 mRNA-5671 的 I 期試驗中的第一位患者已接受注射。

As a reminder, KRAS is a key regulator of cell proliferation and survival.

提醒一下，KRAS 是細胞增殖和存活的關鍵調節因子。

Mutation in the KRAS gene cause disregulated cell proliferation and it's one of the best studied oncogenes.

KRAS 基因突變會導致細胞增殖失調，它是研究最深入的癌基因之一。

It is the most commonly mutated oncogene and it drives over 20% of human cancers, predominantly in the pancreatic, lung and colorectal cancers.

它是最常見的突變癌基因，導致超過 20% 的人類癌症，主要是胰腺癌、肺癌和結直腸癌。

Indeed, the team at the NCI led by Steve Rosenberg had shown at the end of 2016 that the recognition of a mutated KRAS epitope by T cells can lead to cancer [regression].

事實上，由 Steve Rosenberg 領導的 NCI 團隊已於 2016 年底證明，T 細胞識別突變的 KRAS 表位可以導致癌症[消退]。

A quick overview of mRNA-5671 is shown on Slide 21.

幻燈片 21 顯示了 mRNA-5671 的快速概述。

It encodes for the 4 most prevalent mutations of KRAS, which together represent 80% to 90% of KRAS mutations.

它編碼 ​​KRAS 4 個最常見的突變，這些突變合計佔 KRAS 突變的 80% 至 90%。

The genetic sequences that span the mutations are combined into a single mRNA that encodes for all 4 neoantigens.

跨越突變的基因序列被組合成一個編碼所有 4 種新抗原的 mRNA。

When translated within the cell and to a neoantigen protein chain, the cellular [protozonal] machinery is expected to clear the chain and present these neoantigens to the immune system to stimulate what we hope will be an active anticancer T cell response.

當在細胞內翻譯成新抗原蛋白鏈時，細胞[原帶]機制有望清除該鏈並將這些新抗原呈遞給免疫系統，以刺激我們希望的主動抗癌T細胞反應。

The Phase I trial for this vaccine, which is being run by our partner, Merck, has enrolled its first patient, and the study will evaluate safety and tolerability of mRNA-5671, both as monotherapy and in combination with KEYTRUDA in patients with metastatic non-small cell, lung, colorectal and pancreatic cancers that harbor the KRAS mutations.

該疫苗的I 期試驗由我們的合作夥伴默克(Merck) 進行，已招募了第一位患者，該研究將評估mRNA-5671 的安全性和耐受性，無論是作為單一療法還是與KEYTRUDA 聯合治療轉移性非-攜帶 KRAS 突變的小細胞癌、肺癌、結直腸癌和胰腺癌。

Of note in this trial, we are selecting for specific HLA subtypes that based on designs are most likely to respond.

值得注意的是，在本試驗中，我們根據設計選擇最有可能產生反應的特定 HLA 亞型。

For the intratumoral immuno-oncology programs, we are progressing with all 3 of our development candidates; OX40 ligand, the Triplet and interleukin 12.

對於腫瘤內免疫腫瘤學項目，我們正在開發所有 3 個候選藥物； OX40 配體、三聯體和白細胞介素 12。

Starting with mRNA-2416, which encodes for OX40 ligand, which you will recall is a potent co-stimulator that promotes T cell proliferation.

從 mRNA-2416 開始，它編碼 OX40 配體，您會記得它是一種促進 T 細胞增殖的有效共刺激劑。

The Phase I is completing the dose confirmation cohort at 8 milligram and in parallel we're progressing to start the Phase II cohort in patients with advanced ovarian cancer.

第一階段正在完成 8 毫克的劑量確認隊列，同時我們正在著手啟動晚期卵巢癌患者的第二階段隊列。

Slide 26 shows a schematic of the Phase I trial and the Phase II cohort.

幻燈片 26 顯示了 I 期試驗和 II 期隊列的示意圖。

Turning to mRNA-2752, or the Triplet, which encodes for OX40 ligand and 2 proinflammatory cytokines, interleukin 23 and interleukin 36 gamma.

轉向 mRNA-2752，或三聯體，它編碼 OX40 配體和 2 種促炎細胞因子：白細胞介素 23 和白細胞介素 36 γ。

The rationale here was to stimulate T cells through the presence of OX40 ligand while attracting the T cells to the tumor site with the local expression of these cytokines.

這裡的基本原理是通過 OX40 配體的存在刺激 T 細胞，同時通過這些細胞因子的局部表達將 T 細胞吸引到腫瘤部位。

By injecting the tumors directly, we expect the cytokines to act locally within the tumor microenvironment.

通過直接注射腫瘤，我們期望細胞因子在腫瘤微環境中局部發揮作用。

The Phase I is ongoing and has both the monotherapy arm and a combination arm with durvalumab.

I 期正在進行中，有單一療法組和 durvalumab 聯合療法。

I'm pleased to report that the first patient in the combination arm with durvalumab has been dosed.

我很高興地報告，durvalumab 聯合治療組中的第一位患者已經接受了給藥。

We've also made progress with MEDI1191 in our interleukin 12 intratumor injection program, partnered with AstraZeneca, as the first patient in this trial was dosed.

我們與阿斯利康合作的白細胞介素 12 腫瘤內註射項目中的 MEDI1191 也取得了進展，作為該試驗中的第一位患者接受了給藥。

Recall that interleukin 12 is a potent immunomodulators associated with a type 1 interferon response and production of interferon gamma.

回想一下，白細胞介素 12 是一種有效的免疫調節劑，與 1 型乾擾素反應和乾擾素 γ 的產生相關。

Its activity against cancer has been described in the literature, but safety has been a problem when interleukin 12 has being administered systemically.

文獻中已描述了其抗癌活性，但全身施用白細胞介素 12 時，安全性一直是個問題。

We believe that the intratumoral mRNA approach should allow for interleukin 12 to act locally in the tumor microenvironment while avoiding the toxicity seen with systemic administration.

我們認為，腫瘤內 mRNA 方法應允許白細胞介素 12 在腫瘤微環境中局部發揮作用，同時避免全身給藥所出現的毒性。

Let me touch for a moment on the localized regenerative therapeutics and AZD801 (sic) [AZD8601].

讓我談談局部再生療法和 AZD801（原文如此）[AZD8601]。

The Phase IIa in coronary arterial bypass graft population is ongoing.

冠狀動脈旁路移植人群的 IIa 期正在進行中。

Our partner, AstraZeneca, continues to open additional sites in Europe with a clinical trial application now also open in Germany.

我們的合作夥伴阿斯利康繼續在歐洲開設更多站點，目前在德國也開放了臨床試驗申請。

Let me move ahead to our systemic secreted therapeutics, and I will focus on mRNA-1944, our antibody against the chikungunya virus.

讓我繼續討論我們的系統性分泌療法，我將重點關注 mRNA-1944，即我們針對基孔肯雅病毒的抗體。

As of today, we have enrolled 6 of the 8 subjects in the third dose cohort.

截至今天，我們已將 8 名受試者中的 6 名納入第三劑量隊列。

Before I get to the trial design and the strategy among this program, I wanted to take a few minutes to highlight the program which is DARPA funded.

在介紹該項目的試驗設計和策略之前，我想花幾分鐘時間重點介紹一下由 DARPA 資助的項目。

mRNA-1944 encodes for an antibody against chikungunya.

mRNA-1944 編碼針對基孔肯雅熱的抗體。

Now antibodies are a complex protein that require both a heavy and a light chain to come together to form an active protein.

現在抗體是一種複雜的蛋白質，需要重鍊和輕鏈結合在一起形成活性蛋白質。

So mRNA-1944 actually includes 2 mRNAs, one that encodes for heavy chain and one that encodes for the light chain.

因此 mRNA-1944 實際上包含 2 種 mRNA，一種編碼重鏈，一種編碼輕鏈。

Once formed, we expect the antibody to be secreted into the bloodstream where we will be watching to see if it confers passive immunity against the chikungunya virus as expected.

一旦形成，我們預計抗體會分泌到血液中，我們將觀察它是否如預期那樣賦予針對基孔肯雅病毒的被動免疫力。

On Slide 36, you will see the trial design.

在幻燈片 36 上，您將看到試驗設計。

The key objectives of the trial are to evaluate the safety and tolerability of 4 single ascending doses of mRNA-1944 and to evaluate the pharmacokinetics of the drug and the pharmacodynamics of the anti-chikungunya virus antibody levels, which, together will describe the dose response curve.

該試驗的主要目標是評估4 個單次遞增劑量的mRNA-1944 的安全性和耐受性，並評估藥物的藥代動力學和抗基孔肯雅病毒抗體水平的藥效學，這將共同描述劑量反應曲線。

We are collecting assay data to see if the antibody levels neutralize the virus, which we believe will ultimately speak as to whether or not this antibody we encode for is indeed functional.

我們正在收集檢測數據，看看抗體水平是否能中和病毒，我們相信這最終將說明我們編碼的這種抗體是否確實具有功能。

Now the utility of this program is really twofold.

現在這個程序的效用實際上是雙重的。

First, as a product that could potentially protect against chikungunya infection by conferring passive immunity and second, as this program uses the same lipid nanoparticle formulation that is shared with our other programs in the rare disease indications that we're pursuing, it could inform the risk profile of those other programs as well.

首先，作為一種可能通過賦予被動免疫力來預防基孔肯雅熱感染的產品，其次，由於該計劃使用與我們正在尋求的罕見疾病適應症中的其他計劃共享的相同脂質納米顆粒配方，因此它可以告知這些其他計劃的風險狀況也是如此。

Lastly, on systemic intracellular therapeutics where we have 4 development candidates, I'll highlight our rare disease programs, methylmalonic acidemia, or MMA, and the closely associated disease, propionic acidemia or PA.

最後，關於全身細胞內療法，我們有 4 個候選藥物，我將重點介紹我們的罕見疾病項目、甲基丙二酸血症或 MMA，以及密切相關的疾病、丙酸血症或 PA。

Both MMA and PA are inborn errors of protein metabolism that are caused by mute enzyme deficiency and PCC deficiency, respectively.

MMA和PA都是蛋白質代謝的先天性缺陷，分別是由沉默酶缺乏和PCC缺乏引起的。

As you can see, these 2 acidemias are really on the same metabolic pathway.

正如您所看到的，這兩種酸血症實際上處於同一代謝途徑。

Now the prevalence of both is approximately 325 to 2,000 patients in the U.S. Patients are identified during newborn screening and current regimens are palliatives; they consist of strict diet restrictions and oral and IV medications.

現在，在美國，這兩種疾病的患病率約為 325 至 2,000 名患者。患者是在新生兒篩查過程中發現的，目前的治療方案只是姑息治療；它們包括嚴格的飲食限制以及口服和靜脈注射藥物。

Really the best treatment that we currently have available for suitable patients today is a liver transplant.

事實上，我們目前可以為合適的患者提供的最佳治療方法是肝移植。

Both mRNA-3704 and mRNA-3927 encode for intracellular proteins that act within the liver cell and act on the mitochondria.

mRNA-3704 和 mRNA-3927 均編碼在肝細胞內起作用並作用於線粒體的細胞內蛋白質。

Both programs also have FDA orphan drug designation, EMA orphan drug status and FDA rare pediatric disease designation, which upon approval will qualify the 2 programs for rare pediatric disease vouchers.

這兩個項目還擁有 FDA 孤兒藥資格、EMA 孤兒藥資格和 FDA 罕見兒科疾病資格，一旦獲得批准，這兩個項目將有資格獲得罕見兒科疾病優惠券。

The Phase I study of our sentinel rare disease program in MMA with mRNA-3704 currently has 3 sites open and we are actively recruiting patients.

我們的 mRNA-3704 MMA 前哨罕見病項目的 I 期研究目前已開放 3 個研究中心，我們正在積極招募患者。

In parallel, the natural history study continues to enroll well, with a total of 71 patients across both MMA and PA enrolled.

與此同時，自然史研究的入組情況繼續良好，MMA 和 PA 共有 71 名患者入組。

Let me close with Slide 42 which shows you the breadth of our pipeline in one place.

讓我以幻燈片 42 作為結束語，它向您展示了我們在一個地方的管道的廣度。

You will see all the new updates we've announced since December 2018 when we became a public company.

您將看到自 2018 年 12 月我們成為上市公司以來我們宣布的所有新更新。

And with that, let me turn the call over to Lorence.

接下來，讓我把電話轉給洛倫斯。

Thanks, Tal.

謝謝，塔爾。

In today's press release, we reported our second quarter 2019 financial results.

在今天的新聞稿中，我們報告了 2019 年第二季度的財務業績。

Please note these results are unaudited.

請注意，這些結果未經審計。

We ended Q2 2019 with cash, cash equivalents and investments of $1.44 billion.

截至 2019 年第二季度，我們的現金、現金等價物和投資為 14.4 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。

We are reiterating today our expectation for cash, cash flows and investments at December 31, 2019, to be in the range of $1.15 billion to $1.20 billion, consistent with the guidance given on our call in March.

今天，我們重申對 2019 年 12 月 31 日現金、現金流和投資的預期為 11.5 億至 12 億美元，與我們 3 月份電話會議中給出的指導一致。

We remain focused on allocation of our shareholder capital towards value-driving investments in our portfolio and platform.

我們仍然專注於將股東資本分配給我們的投資組合和平台的價值驅動型投資。

Net cash used in operating activities was $256 million for the first 6 months of 2019 compared to $160 million in 2018.

2019 年前 6 個月經營活動使用的現金淨額為 2.56 億美元，而 2018 年為 1.6 億美元。

These numbers include $22 million and $25 million of in-licensing payments in the first quarters of 2019 and 2018, respectively, as stated in the footnote.

如腳註所述，這些數字包括 2019 年第一季度和 2018 年第一季度分別支付的 2200 萬美元和 2500 萬美元的許可付款。

After the first quarter of 2019, we have no further in-licensing payment obligations to Cellscript and its affiliates.

2019 年第一季度之後，我們不再向 Cellscript 及其附屬公司支付許可付款義務。

Cash used for purchases of property and equipment was $18 million in the first 6 months of 2019 compared to $66 million in 2018.

2019 年前 6 個月用於購買財產和設備的現金為 1,800 萬美元，而 2018 年為 6,600 萬美元。

And then on revenue, recall that on January 1, 2019, we adopted the mandated revenue recognition standard ASC606 using the modified retrospective transition method applied to these contracts which were not completed as of January 1, 2019.

然後在收入方面，請回想一下，2019 年 1 月 1 日，我們採用了強制性收入確認標準 ASC606，並使用適用於截至 2019 年 1 月 1 日尚未完成的這些合同的修改後的追溯過渡法。

The decrease in total revenue for Q2 on the first 6 months of 2019 as compared to 2018 was mainly attributable to this adoption of the new revenue standard.

2019年前6個月第二季度總收入較2018年下降的主要原因是採用新收入準則。

Revenue for Q2 2019 was $13 million as compared to $29 million for Q2 2018.

2019 年第二季度的收入為 1300 萬美元，而 2018 年第二季度的收入為 2900 萬美元。

And for the first 6 months of 2019, revenue was $29 million compared to $58 million in 2018.

2019 年前 6 個月的收入為 2900 萬美元，而 2018 年為 5800 萬美元。

Total revenue under the previous revenue recognition standard would have been $17 million for Q2 2019 and $55 million for the first 6 months of 2019.

根據之前的收入確認標準，2019 年第二季度的總收入為 1700 萬美元，2019 年前 6 個月的總收入為 5500 萬美元。

R&D expenses for Q2 2019 were approximately $128 million compared to $104 million for Q2 2018.

2019 年第二季度的研發費用約為 1.28 億美元，而 2018 年第二季度的研發費用為 1.04 億美元。

And for the first 6 months of 2019, R&D expenses were $259 million compared to $195 million in 2018.

2019 年前 6 個月，研發費用為 2.59 億美元，而 2018 年為 1.95 億美元。

The increases in Q2 and the first 6 months of 2019 as compared to 2018 were primarily due to an increase in personnel-related costs, including stock-based compensation, an increase in clinical trial and manufacturing costs, an increase in lab supplies and materials, and an increase in consulting and outside services.

與 2018 年相比，2019 年第二季度和前 6 個月的增長主要是由於人員相關成本的增加，包括基於股票的薪酬、臨床試驗和製造成本的增加、實驗室用品和材料的增加、以及諮詢和外部服務的增加。

G&A expenses for Q2 2019 were approximately $29 million compared to $21 million in Q2 of 2018.

2019 年第二季度的一般管理費用約為 2900 萬美元，而 2018 年第二季度為 2100 萬美元。

And for the first 6 months of 2019, G&A expenses were $56 million compared to $38 million in 2018.

2019 年前 6 個月，一般管理費用為 5600 萬美元，而 2018 年為 3800 萬美元。

The increases in Q2 and the first 6 months of 2019 as compared to 2018 were mainly due to the additional costs of operating as a publicly traded company, including an increase in personnel-related costs and stock-based compensation, consulting and outside services and insurance costs.

與 2018 年相比，2019 年第二季度和前 6 個月的增長主要是由於作為上市公司運營的額外成本，包括人員相關成本和股票薪酬、諮詢和外部服務以及保險的增加成本。

And with that, I'll hand the call back over to Stéphane.

然後，我會將電話轉回給 Stéphane。

Thank you, Lorence.

謝謝你，洛倫斯。

To close our remarks, I would like to reiterate that our team is focused on executing on 3 priorities: advancing the development pipeline, investing in new development candidates in the existing 6 modalities and [investing] in new modalities.

在結束我們的發言時，我想重申，我們的團隊專注於執行 3 個優先事項：推進開發渠道、投資現有 6 種模式中的新開發候選者以及[投資]新模式。

The team at Moderna executed across the board during the quarter.

Moderna 團隊在本季度全面執行。

To summarize quickly the highlights of the quarter.

快速總結本季度的亮點。

We initiated the PCV Phase II trial with first patients consenting to participate in the trial.

我們啟動了 PCV II 期試驗，第一批患者同意參加該試驗。

Our CMV vaccine study is fully enrolled.

我們的 CMV 疫苗研究已全部入組。

We started 4 new clinical trials, 2 in immuno-oncology and 2 in infectious disease.

我們啟動了 4 項新的臨床試驗，其中 2 項針對免疫腫瘤學，2 項針對傳染病。

Vertex cystic fibrosis research collaboration.

Vertex 囊性纖維化研究合作。

As you might recall, in July 2016, Moderna and Vertex announced an exclusive research collaboration and licensing agreement aimed at the discovery and development of mRNA therapeutics for the treatment of CF.

您可能還記得，2016 年 7 月，Moderna 和 Vertex 宣布了一項獨家研究合作和許可協議，旨在發現和開髮用於治療 CF 的 mRNA 療法。

Based on preclinical work today, Vertex has extended this collaboration for the first quarter of 2020 with options to extend further based on future progress.

根據今天的臨床前工作，Vertex 已將這種合作延長至 2020 年第一季度，並可選擇根據未來的進展進一步延長。

Pulmonary mRNA delivery represents a potential new route of administration for Moderna.

肺部 mRNA 遞送代表了 Moderna 的一種潛在的新給藥途徑。

I am pleased with the progress we've made today and look forward to the rest of 2019 and 2020 as we approach critical data readout.

我對我們今天取得的進展感到高興，並期待 2019 年和 2020 年的剩餘時間，因為我們即將讀出關鍵數據。

I will particularly look for the CMV Phase I data and the chikungunya antibody Phase I data in the near term.

近期我會特別關注CMV I期數據和基孔肯雅抗體I期數據。

As a reminder, the chikungunya antibody is the first monoclonal antibody encoded by mRNA technology to be dosed in a human.

需要提醒的是，基孔肯雅病毒抗體是第一個通過 mRNA 技術編碼、用於人體給藥的單克隆抗體。

Because RSV and Zika [are both] in healthy subject, these trials should complete soon and if positive, we intend to transition to Phase II.

由於 RSV 和 Zika 都在健康受試者中，因此這些試驗應該很快完成，如果呈陽性，我們打算過渡到第二階段。

We now have 5 immuno-oncology programs in the clinic, 2 of which are already building in combination with approved checkpoint inhibitors, Merck's KEYTRUDA for PCV and AstraZeneca IMFINZI for Triplet.

我們現在在診所有 5 個免疫腫瘤學項目，其中 2 個項目已經與已批准的檢查點抑製劑（默克用於 PCV 的 KEYTRUDA 和阿斯利康用於 Triplet 的 IMFINZI）聯合開發。

Our teams working with clinical trial sites are focused on the milestone of dosing of first patients with MMA.

我們與臨床試驗中心合作的團隊專注於第一批 MMA 患者用藥這一里程碑。

We believe mRNA has the potential to be a new class of medicine.

我們相信 mRNA 有潛力成為一類新的藥物。

We see a large product opportunity ahead of us and we are energized by the potential to bring these important medicines to patients.

我們看到了巨大的產品機會擺在我們面前，我們對將這些重要藥物帶給患者的潛力感到充滿活力。

Four vaccines for large unmet medical needs where there is no vaccines approved today.

四種疫苗可滿足目前尚未批准疫苗的大量未滿足的醫療需求。

That is a unique opportunity, to help millions and as such, create large commercial products.

這是一個獨特的機會，可以幫助數百萬人創造大型商業產品。

Five immuno-oncology programs, which all have the potential to improve the response of PD-1 or PD-L1 checkpoint inhibitors.

五個免疫腫瘤學項目都有可能改善 PD-1 或​​ PD-L1 檢查點抑製劑的反應。

Five are disease programs for conditions like MMA and PA where [children's bond with the] detected protein urgently need the treatment [that targets] the underlying cause of their disease.

五是針對 MMA 和 PA 等疾病的疾病計劃，在這些疾病中，[兒童與]檢測到的蛋白質的聯繫迫切需要針對其疾病的根本原因進行治療。

The cardiology program, VEGF, which could transform the care of patients with severe (inaudible).

心髒病學項目 VEGF 可以改變重症患者（聽不清）的護理。

And it's only the first wave of innovative products.

這只是第一波創新產品。

Stephen Hoge and his team are working hard to move new innovative development candidates from the labs, into the clinic.

Stephen Hoge 和他的團隊正在努力將新的創新開發候選者從實驗室轉移到臨床。

The productivity of our mRNA platform is significant.

我們的 mRNA 平台的生產力非常顯著。

We built our first clinical trial in December 2015.

我們於 2015 年 12 月開展了第一個臨床試驗。

In just 3.5 years, we started 16 programs in the clinic and we have had a high success rate.

在短短 3.5 年的時間裡，我們在診所啟動了 16 個項目，並且取得了很高的成功率。

The team did get 19 IND off CTAs opened by local authorities.

該團隊確實從地方當局開設的 CTA 中獲得了 19 個 IND。

We know we have a special opportunity and we are committed to delivering on the promise of our science and bringing forward a new class of medicines to patients.

我們知道我們有一個特殊的機會，我們致力於兌現我們科學的承諾，為患者提供新型藥物。

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

在結束我們的發言時，我想感謝參與我們臨床研究的許多人，包括患者、健康志願者和醫生。

I would also like to thank the great team of Moderna employees working hard every day to make our vision a reality.

我還要感謝 Moderna 優秀的員工團隊每天努力工作，使我們的願景成為現實。

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

至此，我們現在很樂意回答任何問題。

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

（操作員說明）我們的第一個問題來自高盛的 Salveen Richter。

This is Andrea on for Salveen.

我是薩爾文的安德里亞。

My first one is how are you thinking about positioning for your KRAS vaccine in the context of growing competition in this space?

我的第一個問題是，在這個領域競爭日益激烈的背景下，您如何考慮 KRAS 疫苗的定位？

And then I have a follow-up.

然後我有一個後續行動。

This is Tal.

這是塔爾。

Look, first of all, I'm really happy that we finally have therapies that are emerging as effective against KRAS mutations.

首先，我真的很高興我們終於有了針對 KRAS 突變有效的療法。

I think that progress for the field is tremendous.

我認為該領域的進步是巨大的。

I think it's still early days, so let me make 2 points.

我認為現在還為時過早，所以讓我提出兩點。

First, the exact nature of the activity and against which mutations and in our case, which mutations and which HLA still needs to be defined.

首先，活性的確切性質以及針對哪些突變，在我們的例子中，哪些突變和哪些 HLA 仍然需要定義。

So I don't see them even on, if you look at the patient distribution, necessarily as competing.

因此，如果你看看患者的分佈情況，我什至看不到它們，必然是相互競爭的。

Second, and I think more importantly, on the fundamentals, I think what our vaccine is trying to do and what the emerging inhibitors are trying to do are very different things in terms of patient benefit.

其次，我認為更重要的是，從基本面來看，我認為我們的疫苗試圖做的事情和新興抑製劑試圖做的事情在患者利益方面是非常不同的。

I think the history of small molecule targeted therapies has been terrific in the sense that it has translated into real benefit for these patients.

我認為小分子靶向治療的歷史非常悠久，因為它已經為這些患者帶來了真正的好處。

But we've struggled to turn them into [curative] treatments.

但我們一直在努力將它們轉化為[治療]療法。

I think on the other hand, the immuno-oncology approaches were successful, have translated into a much more durable effect.

我認為另一方面，免疫腫瘤學方法是成功的，已經轉化為更持久的效果。

And so my expectation is, down the road, if both of these approaches are successful, you would expect them to have complementary benefits for the patients.

因此，我的期望是，如果這兩種方法都成功，您會期望它們能為患者帶來互補的好處。

And I'm -- yes, I'm really excited in the coming years to see how that story plays out.

是的，我真的很興奮在未來幾年看到這個故事如何發展。

And let me -- Stéphane -- just to add one thing.

讓我——Stéphane——補充一件事。

As Tal described in his remarks, the mRNA that we designed is actually coding for 4 mutations G12D, G12V, G13D and G12C.

正如 Tal 在他的發言中所描述的，我們設計的 mRNA 實際上編碼 4 個突變 G12D、G12V、G13D 和 G12C。

And then just on your MMA program.

然後就開始你的 MMA 課程。

How many patients right now are enrolling in your clinical study that have been rolled over from the natural history study?

目前有多少患者正在參加您的臨床研究，這些患者是從自然歷史研究中轉過來的？

So in the clinical study, we have not yet enrolled.

所以在臨床研究方面，我們還沒有入組。

We're actively recruiting.

我們正在積極招募。

In the natural history study, there have been 71 patients enrolled to date.

在自然史研究中，迄今為止已有 71 名患者入組。

Sorry.

對不起。

Do you anticipate, I guess, rolling any patients over from that national natural history study or not?

我想，您是否預計會從該國家自然歷史研究中剔除任何患者？

It is a possibility.

這是一種可能性。

We're looking at it.

我們正在研究它。

Our next question comes from Matthew Harrison of Morgan Stanley.

我們的下一個問題來自摩根士丹利的馬修·哈里森。

Two for me.

給我兩個。

So the first one is, can you just comment broadly how we should think about safety so far in the chikungunya study given that you're through almost the third cohort?

第一個問題是，考慮到您已經完成了幾乎第三組研究，您能否廣泛評論一下迄今為止在基孔肯雅熱研究中我們應該如何考慮安全性？

I don't know if you can comment on what the stopping rules are from a safety standpoint.

不知道您能否從安全角度評論一下停車規則是什麼。

And then a second question is on OX40 ligand.

第二個問題是關於 OX40 配體。

Can you talk about what do you need to do in this Phase II study to be able to take back to the FDA -- I mean, I guess what I'm asking is how should we think about potential regulatory path forward with that molecule?

你能談談在這項二期研究中你需要做什麼才能向 FDA 匯報——我的意思是，我想我要問的是我們應該如何考慮該分子的潛在監管路徑？

Sure.

當然。

Look, let me start with the chikungunya.

聽著，讓我從基孔肯雅熱開始。

This study is ongoing, so I can't really comment on the data until we see the totality of the picture there -- and then we'll describe it for you.

這項研究正在進行中，因此在我們看到整體情況之前我無法對數據做出真正的評論 - 然後我們將為您描述它。

It's a healthy volunteer study so stopping rules are what you would expect in these typical studies.

這是一項健康的志願者研究，因此停止規則是您在這些典型研究中所期望的。

In terms of OX40 ligand, the regulatory path.

就OX40配體而言，調控路徑。

If you look at where we are expanding into the Phase II cohort, we are going after ovarian cancer.

如果你看看我們正在向 II 期隊列擴展，就會發現我們正在針對卵巢癌。

I think in that setting, checkpoint inhibitors are not yet approved.

我認為在這種情況下，檢查點抑製劑尚未獲得批准。

And so if we can -- and it's because they really have [marginal] activity as monotherapy.

因此，如果我們可以——那是因為它們作為單一療法確實具有[邊際]活性。

If we can demonstrate that the combination has a clear benefit to patients, I think the path to approval will be relatively straightforward.

如果我們能夠證明該組合對患者有明顯的益處，我認為獲得批准的途徑將相對簡單。

So that's how we're looking at it.

這就是我們的看法。

Did that answer your question, Matthew?

這回答了你的問題嗎，馬修？

It did.

它做了。

Thank you.

謝謝。

Our next question comes from Ted Tenthoff with Piper Jaffray.

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

So my question is -- and I apologize if this was asked, but with respect to the Triplet, my concern here is to certainly not activity, especially with durvalumab, but are you doing any special immune safety analysis or any special additional safety analysis just because of the potential potency of the Triplet therapy?

所以我的問題是——如果有人問這個問題，我很抱歉，但對於三聯體，我在這里關心的肯定不是活動，尤其是杜瓦魯單抗，但你們是否正在做任何特殊的免疫安全分析或任何特殊的附加安全分析？因為三聯療法的潛在效力？

Thanks, Ted.

謝謝，特德。

That's a really good question and I wish I had a wiser answer for you.

這是一個非常好的問題，我希望能為您提供更明智的答案。

The reality is that we're looking at the safety -- I think in the traditional way that people do in clinical trials, maybe colored by a better understanding over the years of what the safety profile of the checkpoint inhibitors alone is.

現實是，我們正在關注安全性——我認為以人們在臨床試驗中所做的傳統方式，多年來對檢查點抑製劑單獨的安全性有了更好的了解，這可能會帶來色彩。

And so we're looking for whatever autoimmune phenomena, et cetera, and all the other adverse events that one would expect from checkpoint inhibitor monotherapy.

因此，我們正在尋找任何自身免疫現像等，以及檢查點抑製劑單一療法可能出現的所有其他不良事件。

And assessing very carefully to see whether we exceed it.

並非常仔細地評估我們是否超過了它。

If there's any other safety signal that is attributable to the Triplet, then I think we've got 2 ways of finding it.

如果有任何其他安全信號可歸因於三元組，那麼我認為我們有兩種方法可以找到它。

First, recall we are dosing as monotherapy.

首先，請記住我們的劑量是單一療法。

So that will give us a clear view on the safety profile just of the triplet.

這樣我們就可以清楚地了解三胞胎的安全狀況。

And second, in the combination arm, we're looking carefully at all the clinical characteristics.

其次，在聯合治療組中，我們正在仔細研究所有臨床特徵。

And unfortunately, I think as a field, it's very hard to predict the adverse reactions that one sees -- and they're not very frequent.

不幸的是，我認為作為一個領域，很難預測人們所看到的不良反應——而且它們並不常見。

So all you can do at this point is maintain a careful vigil for what's expected and make sure you're not missing anything unexpected.

因此，此時您所能做的就是對預期的情況保持仔細的警惕，並確保您不會錯過任何意外的情況。

I don't know if that answers the question.

我不知道這是否回答了問題。

I'm not sure I've got a better one.

我不確定我是否有更好的。

That's all right.

沒關係。

That makes a lot of sense.

這很有意義。

I appreciate that.

我很感激。

And then just a really quick high level question.

然後是一個非常快速的高級問題。

With respect to the CF collaboration, are there any novel delivery modalities that are being incorporated for that disease?

關於 CF 合作，是否有針對該疾病的新的遞送方式？

Or is this really [that mean] not just treating lung but really systemic disease?

或者這真的不只是治療肺部疾病而是真正的全身性疾病嗎？

It's Stephen Hoge.

這是斯蒂芬·霍格。

So first of all, it's a research collaboration with Vertex and we're excited to continue it based on preclinical progress to date.

首先，這是與 Vertex 的一項研究合作，我們很高興能夠根據迄今為止的臨床前進展繼續進行該合作。

As a part of our general research activities, we do look broadly at a range of different delivery modalities.

作為我們一般研究活動的一部分，我們確實廣泛研究了一系列不同的交付方式。

We have obviously made progress in 1 direction here but we haven't yet defined a development candidate.

顯然，我們已經在一個方向上取得了進展，但我們尚未確定開發候選者。

At which point, we would probably provide specifics about that.

屆時，我們可能會提供相關細節。

Generally our approach with Vertex in CF has been to address the unmet needs in CF, particularly for those patients who [have all of those needs] -- for CFTR and focusing intensively on the pulmonary disease.

一般來說，我們在 CF 方面使用 Vertex 的方法是解決 CF 中未滿足的需求，特別是對於那些 [具有所有這些需求] 的患者——CFTR 並重點關注肺部疾病。

But obviously without commenting specifically in the CF example, pulmonary delivery is a route of administration that could be valid for other systemic diseases or other applications as well.

但顯然，如果沒有在 CF 示例中進行具體評論，肺部遞送是一種對於其他全身性疾病或其他應用也可能有效的給藥途徑。

Our next question comes from Cory Kasimov of JPMorgan.

我們的下一個問題來自摩根大通的科里·卡西莫夫。

I have 2 as well.

我也有2個。

So I guess, first, can you just walk us through the cadence of what you see as the key validating clinical updates we should expect in the next 12 months or so?

所以我想，首先，您能否向我們介紹一下您認為在未來 12 個月左右的時間裡我們應該期待的關鍵驗證臨床更新的節奏？

I think -- beyond the CMV and chikungunya update, what else has a chance of occurring in that time period?

我想——除了鉅細胞病毒和基孔肯雅熱更新之外，在那段時間裡還有什麼機會發生？

And will we see new clinical data at your R&D day in September?

我們會在九月份的研發日看到新的臨床數據嗎？

And then I have one follow-up.

然後我有一個後續行動。

It's Stéphane.

這是史蒂芬。

So I will not comment on the R&D day.

所以我不會對研發日發表評論。

I hope you come to the R&D Day.

我希望你能來參加研發日。

We will make sure that we give a good update on everything we know then.

我們將確保及時更新我們所知道的一切。

On the next 12 months, as you can see on Slide 46 on the presentation -- as I discussed in my comments, CMV is very important.

在接下來的 12 個月中，正如您在演示文稿的幻燈片 46 中看到的那樣，正如我在評論中討論的那樣，CMV 非常重要。

As you know, we really think it's a very large opportunity.

如您所知，我們確實認為這是一個非常大的機會。

We own 100% of the economic of this product.

我們擁有該產品100%的經濟權。

We believe there's a very large medical need out there.

我們相信那裡有非常大的醫療需求。

And so the CMV data are going to be very important, we believe, for the company.

因此，我們相信 CMV 數據對於該公司來說將非常重要。

RSV and Zika, because they are in Phase I in healthy subjects and they are dosing as we speak should [ready] pretty quickly.

RSV 和寨卡病毒，因為它們在健康受試者中處於第一階段，而且正如我們所說，它們正在給藥，應該很快就會[準備好]。

And that as I shared, the plan is to move those to Phase II, assuming we have good data into the clinic.

正如我所分享的，假設我們有良好的臨床數據，計劃將這些項目轉移到第二階段。

I'll remind you that we have already in the past shown [in a good translation] from primate into humans into [our vaccine have had] positive data.

我要提醒您的是，我們過去已經[以良好的方式]展示了從靈長類動物到人類的[我們的疫苗已經有]積極的數據。

And so we look forward to this data in humans.

所以我們期待在人類身上得到這些數據。

PCV, of course, will take a little bit of time because we started a Phase II, that's a very important study.

當然，PCV 需要一點時間，因為我們開始了第二階段，這是一項非常重要的研究。

We need to recruit for that Phase II, [in all] 150 patients across the board.

我們需要為第二階段招募 150 名患者。

And then it's -- it's, of course, looking at survival in 12 months.

當然，我們還要考慮 12 個月後的生存情況。

KRAS is going to be interesting.

KRAS 將會很有趣。

We all believe there's a big medical need (inaudible) tumor types.

我們都相信腫瘤類型有很大的醫療需求（聽不清）。

So we have [therapy] [in 2] patients in Phase I so we will be sharing observation at the planned clinical meetings of what we see in the clinic.

因此，我們對 [2] 名患者進行了第一階段的[治療]，因此我們將在計劃的臨床會議上分享我們在臨床中看到的觀察結果。

In the intratumoral, because it's oncology and we are dosing -- we prepared it in combination with PD-1 -- OX40 will be in Phase II soon.

在腫瘤內，因為它是腫瘤學，我們正在給藥——我們將其與 PD-1 結合使用——OX40 很快就會進入 II 期。

And also, it will be in combination with a checkpoint.

而且，它將與檢查點結合起來。

(inaudible) IL12.

（聽不清）IL12。

Forward -- same thing.

向前——同樣的事情。

We will update at different medical meetings all the clinical observations [except as recruiting].

我們將在不同的醫學會議上更新所有臨床觀察結果[招募除外]。

And then as we discussed, the CHIK antibody is very important for us.

正如我們所討論的，CHIK 抗體對我們來說非常重要。

And then getting the first [results] in the clinic.

然後在診所獲得第一個[結果]。

The (inaudible) are going to go straight into patients.

（聽不清）將直接進入患者體內。

As we commented before, we are starting MMA at a dose that has been shown in animal models having some benefit.

正如我們之前評論的，我們開始使用 MMA 的劑量已在動物模型中顯示出一些益處。

And so I think the next few months and the next few quarters are going to quite rich, data-wise.

因此，我認為未來幾個月和未來幾個季度的數據將會非常豐富。

We have now (inaudible) testing drugs [for launching] in the clinic.

我們現在（聽不清）正在診所測試藥物[準備推出]。

That's a lot of potential data we have.

我們擁有大量潛在數據。

Okay.

好的。

Great.

偉大的。

And then the follow-up is regarding your personalized cancer vaccine, 4157 program.

接下來是關於您的個性化癌症疫苗，4157 計劃。

Any near-term plans for exploring indications beyond resected melanoma -- patients that are of high risk of relapse or PD-1 refractory?

是否有近期計劃探索切除黑色素瘤以外的適應症——復發風險高或 PD-1 難治性的患者？

And what do you see as the potential of this program in indications that have -- that might have considerably less [neo appetites]?

您認為該計劃的潛力是什麼？（新需求）可能會大大減少？

Thanks for that, Cory.

謝謝你，科里。

It's Tal.

是塔爾。

It's a question that we've asked ourselves since the beginning of this program.

自該計劃開始以來，我們就一直在問自己這個問題。

I think strategically and philosophically what we want to do in this program is first to go where the likelihood of success is the highest before we look for areas that are more challenging.

我認為從戰略和哲學上來說，我們在這個項目中要做的就是首先去成功可能性最高的地方，然後再尋找更具挑戰性的領域。

And so that's why we focused in the histologies that we have in the Phase I and that's why we went into an adjuvant setting even within melanoma for a definitive study to Phase II.

這就是為什麼我們在第一階段專注於組織學，這就是為什麼我們進入輔助環境，甚至在黑色素瘤內進行第二階段的明確研究。

I think once we have a clear proof of concept, clearly, we will begin to explore some of those additional indications.

我認為，一旦我們有了明確的概念證明，我們將開始探索其中一些額外的跡象。

But there's not any current plans to do that.

但目前還沒有任何計劃這樣做。

And Cory, it's Stéphane.

科里，我是斯蒂芬。

To add to Tal's remarks, if you think about it, going back to Lorence's comments, we are very disciplined with capital allocation.

補充一下塔爾的言論，如果你想一想，回到洛倫斯的評論，我們在資本配置方面非常嚴格。

So, of course, there could be a lot of different things one could think of trying with personalized cancer vaccine.

因此，當然，人們可以考慮嘗試多種不同的個性化癌症疫苗。

As you think of it, all the patients [that benefited] today.

正如你所想，今天所有的患者都[受益]。

But unfortunately, we cannot [know] -- before we have an important [derisking], we cannot expand too much because we have so many opportunities of products across our portfolio, we could be increasing the burn to a place that will not be reasonable.

但不幸的是，我們無法[知道]——在進行重要的[降低風險]之前，我們不能擴張太多，因為我們的投資組合中有很多產品的機會，我們可能會增加燒錢到一個不合理的地方。

And so we want to be very disciplined.

所以我們要非常自律。

And I -- just one example, but there's a lot of things, trust me, that the clinical team -- as you know, Tal is an oncologist by training, who loves to be trying in the clinic to help those patients.

我——只是一個例子，但相信我，臨床團隊有很多事情——如你所知，塔爾是一位受過培訓的腫瘤學家，他喜歡在診所嘗試幫助這些患者。

But we just have to be very disciplined with capital allocation and how much we spend and where we spend it and when we spend it based on derisking.

但我們必須在去風險的基礎上嚴格控制資本配置、支出金額、支出地點和時間。

Our next question comes from Alan Carr of Needham.

我們的下一個問題來自李約瑟的艾倫·卡爾。

This is Jennifer speaking for Alan.

我是詹妮弗，代表艾倫發言。

I have a couple of questions.

我有一些問題。

First question is I was wondering if the team can give us some color on the commercial strategy and possibly specific patient groups that you may be planning to target for the CMV assets?

第一個問題是，我想知道團隊是否可以為我們提供一些有關商業策略的信息，以及您可能計劃針對 CMV 資產的特定患者群體？

So thank you, Jennifer, for the question.

謝謝詹妮弗提出的問題。

I think it would be great if you can join us at the R&D Day because we will spend quite some time on CMV commercial opportunity.

我認為如果您能參加我們的研發日那就太好了，因為我們將花相當多的時間在 CMV 商業機會上。

As we discussed in the past, there are many populations from women in the age of bearing a child, adolescent women that you might want to protect, there is a discussion about partners of those pregnant women.

正如我們過去所討論的，有許多人群是您可能想要保護的處於生育年齡的女性、青春期女性，並且存在關於這些孕婦的伴侶的討論。

There is also a discussion because humans are very (inaudible) CMV, do you put down an age to try to eradicate CMV?

還有一個討論，因為人類的CMV非常（聽不清），你是否會設定一個年齡來嘗試根除CMV？

So there's a lot of different segments that we will discuss quite at length on the R&D Day.

因此，我們將在研發日詳細討論許多不同的部分。

But this is why I think we believe CMV -- if you take a 10, 20 year time frame.

但這就是為什麼我認為我們相信 CMV——如果你考慮 10 年、20 年的時間框架的話。

And if you look at the [all the other] vaccines, like the HPV vaccine and the (inaudible) vaccine, those very important vaccines, the lifecycle management of those products can be very important.

如果你看看[所有其他]疫苗，比如 HPV 疫苗和（聽不清）疫苗，這些非常重要的疫苗，這些產品的生命週期管理可能非常重要。

And we have our eyes very much on how do we go about this.

我們非常關注如何解決這個問題。

Again, we cannot do all the indications at the same time.

再次強調，我們無法同時執行所有指示。

It's going back to discipline on capital allocation and investment.

這又回到了資本配置和投資的紀律上。

But we have very much in mind of how do we maximize [the time] this opportunity to get the largest label that we can for CMV so it can be given to the largest population we can around the world not only in the U.S.

但我們非常清楚如何最大限度地利用這個機會，為鉅細胞病毒獲得盡可能多的標籤，以便將其提供給世界各地最大的人群，而不僅僅是在美國。

And the other question is for the hMPV/PIV3 vaccine, could you possibly give us some comments or color on any new understanding of the titer level needed to progress this asset?

另一個問題是關於 hMPV/PIV3 疫苗，您能否就推進這項資產所需的滴度水平的任何新理解給我們一些評論或意見？

This is Tal.

這是塔爾。

I think that our understanding of the titers there is going to be based mostly on the preclinical modeling and what we've seen to date that is protected.

我認為我們對滴度的理解將主要基於臨床前模型和我們迄今為止所看到的受保護的內容。

Unfortunately, there is no vaccine on the market so we don't really have a correlate of protection like we have from influenza, but it is a respiratory virus so one draws similar parallels from the experience with flu.

不幸的是，市場上沒有疫苗，所以我們實際上沒有像流感那樣的相關保護，但它是一種呼吸道病毒，所以我們可以從流感的經歷中得出類似的相似之處。

And you get a sense from the totality of our understanding and the science on the respiratory virus as what are the titers like.

您可以從我們對呼吸道病毒的整體理解和科學知識中了解滴度是多少。

I think what we've seen in the Phase I is supportive of our ability to immunize.

我認為我們在第一階段所看到的情況支持了我們的免疫能力。

Recall though that the target population here is in seronegative infants, right?

回想一下，這裡的目標人群是血清陰性嬰兒，對嗎？

So ultimately, we're going to have to define our ability to reach significant titers and boost to the maximal immune response capability to respond in that population down the road.

因此，最終，我們必須確定我們達到顯著滴度並增強最大免疫反應能力的能力，以便在未來的人群中做出反應。

So I think it may not be a very black and white answer because I think it will take inference from multiple lines of reasoning from science and from clinical studies and from other vaccines, I think, to come to that.

所以我認為這可能不是一個非常黑白分明的答案，因為我認為這需要從科學、臨床研究和其他疫苗的多種推理中得出結論。

Does that help you?

這對你有幫助嗎？

Yes.

是的。

Thank you.

謝謝。

Our next question comes from Hartaj Singh of Oppenheimer & Co.

我們的下一個問題來自奧本海默公司的 Hartaj Singh。

Great.

偉大的。

I just have 2. One is, I know that you've mentioned that the CHIK antibodies is very important.

我只有 2 個。第一個是，我知道您提到 CHIK 抗體非常重要。

Can you just talk maybe a little bit about then if you see the proof of concept -- you know, manufacturing the antibodies using mRNA and then see efficacy on the vaccine side -- antibodies are over $100 billion in sales per year.

您能否簡單談談一下，如果您看到概念驗證——您知道，使用 mRNA 製造抗體，然後看到疫苗方面的功效——抗體每年的銷售額超過 1000 億美元。

I mean what other areas could you go into?

我的意思是你還可以涉足哪些其他領域？

Would you see yourself being in vaccines?

您會看到自己接種疫苗嗎？

Are there other types of antibodies, other types of diseases that would be amenable to your approach in that regard?

是否有其他類型的抗體、其他類型的疾病適合您在這方面的方法？

Or is that just looking too far into the future?

或者這只是對未來的展望太遠了？

And then I've got a quick follow-up.

然後我會進行快速跟進。

So good morning, it's Stéphane.

早上好，我是斯特凡。

So as you know, we have disclosed 21 development candidates and we don't comment on future plans and research.

如您所知，我們已經披露了 21 個候選開發項目，並且我們不對未來的計劃和研究發表評論。

Obviously, as I said in my remarks, we think it's a very important milestone.

顯然，正如我在發言中所說，我們認為這是一個非常重要的里程碑。

It's the first time that using mRNA technology, an antibody is being produced in a human.

這是首次使用 mRNA 技術在人體中生產抗體。

And so that's an important technology that, as you commented, has a lot of different applications.

正如您所說，這是一項重要的技術，有很多不同的應用。

What we try to do always as the portfolio of the asset that we develop with our shareholder's capital is to be thoughtful about managing biology risk, technology risk and to create important, innovative products for patients.

作為我們用股東資本開發的資產組合，我們始終努力做的是深思熟慮地管理生物風險、技術風險，並為患者創造重要的創新產品。

That's always a big driver for us.

這始終是我們的一大推動力。

If you look back to one of my closing slides, if you look at our portfolio today, for most of the products we have in the pipeline, there is no product on the market that's bigger [than the medical] need and there is no solution in the market.

如果你回顧一下我的一張結束幻燈片，如果你看看我們今天的產品組合，對於我們正在開發的大多數產品，市場上沒有任何產品比醫療需求更大，也沒有解決方案在市場上。

And so we're always thoughtful about those things.

所以我們總是思考這些事情。

But it would be, of course, become a very important tool in our Moderna toolbox.

但它當然會成為我們 Moderna 工具箱中非常重要的工具。

As you know, partnering is also an important part of our strategy.

如您所知，合作也是我們戰略的重要組成部分。

If you go back over time, we've done 4 partnerships with Merck, (inaudible).

如果你回顧過去，我們已經與默克建立了 4 次合作關係（聽不清）。

We are very, of course, happy with the decision by Vertex to expand their collaboration.

當然，我們對 Vertex 擴大合作的決定感到非常高興。

And so that's also -- technology can be made available to a partner.

因此，技術也可以提供給合作夥伴。

So this is an important piece in the Moderna toolbox.

所以這是 Moderna 工具箱中的一個重要部分。

Great.

偉大的。

That helps a lot.

這很有幫助。

And then I just had a question on your manufacturing strategy.

然後我問了一個關於你們的製造策略的問題。

I mean I visited the Norwood facility, really, really kind of cool stuff going on there.

我的意思是我參觀了諾伍德工廠，那裡發生的事情真的非常非常酷。

It is clinical grade sort of material and research material.

它是臨床級材料和研究材料。

Can you just talk a little bit about how you're thinking about your commercial grade material?

您能簡單談談您對商業級材料的看法嗎？

I mean you're getting to the point now where you might have 1 or 2 other rare or diseases where you might be able to get to the clinic very rapidly and the regulators want to see it [as a sort of] clinical to commercial sort of strategy.

我的意思是，你現在可能患有 1 或 2 種其他罕見疾病，你可能能夠非常迅速地到達診所，監管機構希望將其視為一種臨床到商業的類型的策略。

Can you just talk a little bit about that?

你能簡單談談這個嗎？

And then which of your modalities actually requires more intensity from a commercial manufacturing perspective than others?

那麼從商業製造的角度來看，您的哪種方式實際上比其他方式需要更多的強度？

That's a great question.

這是一個很好的問題。

So on the commercial front, as we've shared in the past, Norwood is able to do commercial.

因此，在商業方面，正如我們過去所分享的那樣，諾伍德能夠做商業。

It's not ready today.

今天還沒準備好。

We have to do much work on validation and the quality systems and so on.

我們必須在驗證和質量體係等方面做大量工作。

But the infrastructure of the plant itself has been built so that the site can be brought to commercial readiness and being able to do pivotal studies, registration studies out of Norwood.

但工廠本身的基礎設施已經建成，以便該工廠能夠做好商業準備，並能夠在諾伍德之外進行關鍵研究和註冊研究。

What we also shared and it's again going back to our focus on managing the risk, we will not have to be the commercial facility before we have our first commercial product approved.

我們還分享了，這再次回到了我們對風險管理的關注，在我們的第一個商業產品獲得批准之前，我們不必成為商業設施。

That's a very important part of Moderna strategy to derisk the company.

這是 Moderna 降低公司風險戰略的一個非常重要的部分。

So we cannot produce out of Norwood.

所以我們不能在諾伍德生產。

We can do Phase III out of Norwood.

我們可以在諾伍德進行第三階段。

We will get the facts ready on time so that we can do that.

我們將按時準備好事實，以便我們能夠做到這一點。

We are also always have a contract manufacturer strategy.

我們也始終有合同製造商戰略。

We never want to be single source for the company, that will be way too risky.

我們永遠不想成為公司的單一來源，那風險太大了。

So we have, as we speak, contract manufacturers that have also commercial capabilities from their site and the quality system ready.

因此，正如我們所說，我們擁有合同製造商，他們也擁有其現場的商業能力和質量體系。

And if you think about the different products on the portfolio, which is the second question, the big impact is mostly on the backend, which is on filling device.

如果你考慮產品組合中的不同產品，這是第二個問題，那麼最大的影響主要是在後端，即灌裝設備上。

Because if you think about it, mRNA for vaccines, the dose are very, very tiny so you don't need a lot of mRNA drug substance to supply actually millions of vials because if you go back to the data we have published, our vaccines show efficacy in the 2,500 microgram type per human -- so [in procure] we can do a lot of -- doses per [liters] you can do the math.

因為如果你想一想，疫苗的 mRNA 劑量非常非常小，所以你不需要大量的 mRNA 藥物來供應實際上數百萬瓶，因為如果你回顧一下我們發布的數據，我們的疫苗顯示每人2,500 微克類型的功效- 所以[在採購]我們可以做很多- 每[升]劑量你可以做數學。

And so, and [for the record] this is because the n of patients is low, you also don't go into gigantic quantities.

因此，[鄭重聲明]這是因為患者數量很少，因此您也不會投入大量患者。

But of course, oncology, it's a different ballgame.

但當然，對於腫瘤學來說，這是一個不同的遊戲。

But again, that will be a very happy program to manage when we get there.

但同樣，當我們到達那裡時，這將是一個非常令人愉快的管理計劃。

On the backend, Norwood does not have the ability to do millions of vials of fillings.

在後端，諾伍德沒有能力進行數百萬瓶灌裝。

But that is something that is [realizable] through contract manufacturing.

但這是可以通過合同製造[實現]的。

So that is why we feel very confident that we have the -- with the current infrastructure that we have, we have the ability to do pivotal, to do commercial.

這就是為什麼我們非常有信心，憑藉我們現有的基礎設施，我們有能力做關鍵的、做商業的事情。

If we have to manage the backend with more vial capacity, we will get and contract that out with an existing partner or a new partner, we have planned for that.

如果我們必須管理具有更多瓶子容量的後端，我們將與現有合作夥伴或新合作夥伴簽訂合同，我們已經計劃了這一點。

And if we needed more capacity, one thing to remember about Norwood is that we can increase the capacity of Norwood tremendously versus the current capacity.

如果我們需要更多容量，關於諾伍德需要記住的一件事是，與當前容量相比，我們可以極大地增加諾伍德的容量。

We are only working with 2 day shifts.

我們只實行 2 天輪班制。

We could put, course, a night shift.

當然，我們可以安排夜班。

We don't have a shift on weekends.

我們週末沒有輪班。

So right there you have a lot of capacity available.

因此，您有大量可用容量。

We can move the warehouse out of the site.

我們可以把倉庫搬出工地。

The warehouse doesn't have to be on the site -- and you have, by the way, more GMP facilities that you can access your utilities.

倉庫不必位於現場 - 順便說一句，您擁有更多 GMP 設施，可以使用您的公用設施。

The QC lab can also be moved out of the plant.

QC 實驗室也可以搬出工廠。

It can be moved on the parking lot -- you just build a new building.

它可以在停車場移動——你只需建造一座新建築。

And here again, you go with more GMP capacity.

在這裡，您需要更多的 GMP 能力。

The -- [pre-clinical], all the robotics are [pre-clinical.] Same thing.

- [臨床前]，所有機器人都是[臨床前]。同樣的事情。

It's currently in a GMP [Swift] but doesn't have to be, because it's pre-clinical material.

它目前處於 GMP [Swift] 階段，但不一定如此，因為它是臨床前材料。

So there again, you can move it to the parking lot on your new building.

因此，您可以將其移至新大樓的停車場。

So if you think about the manufacturing strategy of Moderna, Norwood was a big investment, we think it's a strategic investment.

因此，如果你考慮 Moderna 的製造戰略，諾伍德是一項重大投資，我們認為這是一項戰略投資。

We cannot deliver on the mission of the company or the pipeline without Norwood.

如果沒有諾伍德，我們就無法實現公司或管道的使命。

But we really built Norwood so that this becomes the [central knot] for us, that is there for a very long term so that we don't have to invest CapEx in the years to come at the high-level.

但我們真正建立了諾伍德，以便這成為我們的[中心結]，這是長期存在的，這樣我們就不必在未來幾年進行高水平的資本支出投資。

We will not build a commercial plant until we are product-approved.

在獲得產品批准之前，我們不會建造商業工廠。

That would be way too risky.

那樣的話風險就太大了。

Our next question comes from Alec Stranahan from Bank of America Merrill Lynch.

我們的下一個問題來自美銀美林的亞歷克·斯特拉納漢 (Alec Stranahan)。

I just had a couple.

我剛喝了幾個。

So maybe first on the hMPV/PIV3 combination vaccine.

所以也許首先是 hMPV/PIV3 聯合疫苗。

Do you have a sense of the sort of data we'll likely see in October?

您是否了解我們可能在 10 月份看到的數據類型？

And will we see data outside of the antibody titer comparison?

我們會看到抗體效價比較之外的數據嗎？

And is the Phase Ib toddler study necessary, as per your conversations with the FDA, before you begin a Phase III?

根據您與 FDA 的對話，在開始 III 期研究之前， Ib 期幼兒研究是否必要？

And then I have one more.

然後我還有一個。

Thanks, Alec.

謝謝，亞歷克。

This is Tal.

這是塔爾。

So in October, we'll present the totality of the data as we have it.

因此，在 10 月份，我們將展示現有的全部數據。

So you will see the antibody titers, you will see the total of the safety, you'll see what you typically see when we describe the totality of the study.

因此，您將看到抗體滴度，您將看到總體安全性，您將看到當我們描述研究的整體性時通常會看到的內容。

And, I believe that's been accepted to IDWeek.

而且，我相信 IDWeek 已經接受了這一點。

In terms of the seropositive toddlers, yes, I think that is consistent with the development path that one would expect and that the agency concurs in terms of the next step in the development path here.

就血清反應呈陽性的幼兒而言，是的，我認為這與人們期望的發展道路是一致的，並且該機構也同意這裡發展道路的下一步。

So ultimately, remember that the target population here is infants.

因此，最終請記住，這裡的目標人群是嬰兒。

So there is a pretty structured and rigorous way by which you work your way down into that population.

因此，有一種非常結構化和嚴格的方法可以幫助您深入了解該人群。

Now given the sensitivity to the pediatric population, we wanted to make sure that we've got clarity from the agency in terms of designing that study, and that's why we put it in the press release and we discussed that interaction.

現在考慮到對兒科人群的敏感性，我們希望確保我們在設計該研究方面得到該機構的明確說明，這就是我們將其放在新聞稿中並討論這種相互作用的原因。

Right, right.

是的是的。

I understand that's a sensitive patient population.

我知道這是一個敏感的患者群體。

And then shifting gears to your KRAS vaccine, 5671.

然後轉向 KRAS 疫苗 5671。

We've seen data from Amgen and others that are pretty encouraging on G12C, although it seems maybe there is a subgroup that requires additional combination therapies.

我們已經看到來自 Amgen 和其他公司的 G12C 數據非常令人鼓舞，儘管似乎有一個亞組需要額外的聯合療法。

So I was just curious, on the KRAS vaccine, what your thoughts are for those monotherapy?

所以我很好奇，對於 KRAS 疫苗，您對單一療法有何看法？

And also in terms of combination with checkpoint inhibitors?

以及與檢查點抑製劑的組合？

So I'll give you 2 versions of the answer, one on the science and one as a drug developer.

所以我會給你兩個版本的答案，一個是關於科學的，一個是作為藥物開發商的。

On the science, unquestionably, one would want to combine these as early as possible because we think there's orthogonal benefit, as I described previously.

在科學上，毫無疑問，人們希望儘早將這些結合起來，因為我們認為存在正交效益，正如我之前所描述的。

And one would expect that it gets combined with checkpoint inhibitors in addition.

人們還期望它還能與檢查點抑製劑結合使用。

As a drug developer, you want to get confidence first that your -- that each individual has merit on its own before you go into the combination.

作為一名藥物開發商，您首先希望獲得信心，在進行組合之前，每個人都有自己的優點。

I think for us, it's critical to demonstrate that the cancer vaccine as such in combination with a PD-1 inhibitor can actually mediate responses.

我認為對我們來說，證明癌症疫苗本身與 PD-1 抑製劑結合實際上可以介導反應至關重要。

I think once we get to that stage, we will obviously have a keen interest in pursuing the right combinations with the inhibitors depending on where they are at that point in time.

我認為一旦我們到達那個階段，我們顯然會對根據抑製劑當時的情況尋求正確的抑製劑組合產生濃厚的興趣。

Alec, did that answer your question?

亞歷克，這回答了你的問題嗎？

It did.

它做了。

Thank you.

謝謝。

There are no further questions.

沒有其他問題了。

I'd like to turn the call back over to Stéphane Bancel for any closing remarks.

我想將電話轉回給 Stéphane Bancel，讓其作結束語。

Thank you for joining us today, for your questions.

感謝您今天加入我們並提出問題。

We look forward to hosting you during our upcoming third annual R&D Day in New York City.

我們期待在紐約市即將舉行的第三屆年度研發日期間接待您。

This meeting will be held during the morning of September 12.

本次會議將於9月12日上午舉行。

Have a wonderful day.

祝你有美好的一天。

Thank you.

謝謝。

Ladies and gentlemen, thank you for participating in today's conference.

女士們、先生們，感謝你們參加今天的會議。

This does conclude the program and you may all disconnect.

這確實結束了程序，你們都可以斷開連接。

Everyone, have a great day.

大家，祝你有美好的一天。