莫德納 (MRNA) 2023 Q1 法說會逐字稿

Good day, and thank you for standing by. Welcome to Moderna's First Quarter 2023 Conference Call. (Operator Instructions) Please be advised today's conference is being recorded.

您好，感謝您的支持。歡迎參加 Moderna 2023 年第一季電話會議。 （操作員指示）請注意，今天的會議正在錄音。

I would now like to hand the conference over to your speaker today, Lavina Talukdar. Please go ahead.

現在我想將會議交給今天的發言人拉維娜·塔魯克達 (Lavina Talukdar)。請繼續。

Thank you, Kevin. Good morning, everyone, and thank you for joining us on today's call to discuss Moderna's First Quarter 2023 Financial Results and Business Update. You can access the press release issued this morning as well as the slides that we'll be reviewing by going to the Investors Section of our website.

謝謝你，凱文。大家早安，感謝您參加今天的電話會議，討論 Moderna 2023 年第一季財務業績和業務更新。您可以造訪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要審查的幻燈片。

On today's call are Stephane Bancel, our Chief Executive Officer; Stephen Hoge, our President; Arpa Garay, our Chief Commercial Officer; and Jamey Mock, our Chief Financial Officer.

參加今天電話會議的有我們的執行長 Stephane Bancel；我們的總裁 Stephen Hoge； Arpa Garay，我們的財務長；以及我們的財務長 Jamey Mock。

Before we begin, please note that this conference call will include forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

在我們開始之前，請注意，本次電話會議將包括根據 1995 年《私人證券訴訟改革法》的安全港條款所作的前瞻性陳述。

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.

請參閱隨附簡報的第 2 張投影片和我們向美國證券交易委員會 (SEC) 提交的文件，以了解可能導致我們的實際業績和結果與這些前瞻性陳述中明示或暗示的業績和結果存在重大差異的重要風險因素。

With that, I will turn the call over to Stephane.

說完這些，我將把電話轉給史蒂芬 (Stephane)。

Thank you, Lavina. Good morning or good afternoon, everyone. Today, I will start with a business review Stephen will then review our clinical programs before Arpa gives an update on our commercial progress and plans. Jamey will present our financial results, and I will come back to close.

謝謝你，拉維娜。大家早安或下午好。今天，我將首先進行業務審查，然後 Stephen 將審查我們的臨床項目，之後 Arpa 將介紹我們的商業進展和計劃。 Jamey 將介紹我們的財務業績，然後我會回來結束演講。

So in the first quarter, we recorded revenues of $1.9 billion, GAAP net income of $79 million and GAAP diluted earnings per share of $0.19. Cash and cash investments of $16.4 billion at the end of the quarter. We continued in Q1, executing on our capital allocation strategy, prioritizing investments in our business. In the first quarter, we invested $1.1 billion in R&D, continuing investment in late stage clinical programs and progressing by entire pipeline.

因此，在第一季度，我們的營收為 19 億美元，GAAP 淨收入為 7,900 萬美元，GAAP 稀釋每股收益為 0.19 美元。本季末的現金和現金投資為 164 億美元。我們在第一季繼續執行資本配置策略，優先投資我們的業務。第一季度，我們在研發方面投資了 11 億美元，繼續投資後期臨床專案並推動整個研發管線。

SG&A costs were approximately $400 million in the quarter, which include investments in digital and also AI infrastructure and approximately $100 million in capital investments. In 2023, our (inaudible) team has been very active. This includes the acquisition of OriCiro in Japan, collaboration with CytomX, Life Edit and Generation Bio. All of these investment opportunities further expand the reach of Moderna's mRNA technology.

本季銷售、一般及行政費用約為 4 億美元，其中包括對數位和人工智慧基礎設施的投資以及約 1 億美元的資本投資。 2023 年，我們的（聽不清楚）團隊非常活躍。其中包括收購日本的 OriCiro，以及與 CytomX、Life Edit 和 Generation Bio 的合作。所有這些投資機會進一步擴大了 Moderna mRNA 技術的覆蓋範圍。

We are growing Moderna mRNA operating system. $526 million were returned to shareholders with share purchase of 3.6 million shares in the quarter. Let me turn to Commercial in the first quarter.

我們正在開發 Moderna mRNA 作業系統。本季透過購買 360 萬股股票向股東返還了 5.26 億美元。讓我來談談第一季的商業。

We continue to expect $5 billion in COVID vaccine deliveries in 2023 from already signed advanced purchase agreements. With $1.8 billion of COVID sales in Q1, we are well on our way to achieve $5 billion in APS. The commercial team is actively negotiating to sign new contracts with customers in major markets to finalize additional orders that will add to the $5 billion. The U.S. team is negotiating with pharmacy chains, hospital networks and other customers.

我們繼續預計，根據已簽署的預購協議，2023 年 COVID 疫苗交付將達到 50 億美元。第一季度，COVID 銷售額達到 18 億美元，我們預計將實現 50 億美元的 APS 銷售額。商業團隊正在積極與主要市場的客戶談判簽署新合同，以最終確定將達到 50 億美元規模的額外訂單。美國團隊正在與連鎖藥局、醫院網路和其他客戶進行談判。

As a reminder, the $5 billion of signed APAs does not include any fall of 2023 U.S. contracts. So these new U.S. commercial contracts are important to the business as they are additional. The team is also making progress in Japan, in Europe and other countries in Asia, Middle East and also Latin America. We recently signed a new contract in Australia for 2023. Our commercial organization is also preparing for the launch of RSV in 2024. Our next respiratory commercial products. They're educating the medical community on the health burden of RSV. Our medical team is participating in major infectious disease medical congresses and sharing the new data that shows a strong profile of our RSV vaccine. To prepare for our RSV launch, our manufacturing team has already begun producing drug substance, the mRNA molecule for RSV vaccine. The vaccine will be supplied as a prefilled syringe. We believe that will help drive adoption by pharmacists and doctors versus some of our RSV products.

需要提醒的是，已簽署的 50 億美元 APA 並不包括 2023 年秋季簽訂的美國合約。因此，這些新的美國商業合約對於企業來說很重要，因為它們是附加的。該團隊還在日本、歐洲以及亞洲、中東和拉丁美洲的其他國家取得了進展。我們最近在澳洲簽署了一份2023年的新合約。我們的商業組織也正在為2024年推出RSV做準備。我們的下一個呼吸商業產品。他們正在向醫學界宣傳呼吸道合胞病毒對健康的危害。我們的醫療團隊正在參加主要的傳染病醫學大會，並分享顯示我們的 RSV 疫苗強大功效的新數據。為了準備推出 RSV，我們的製造團隊已經開始生產藥物物質，即 RSV 疫苗的 mRNA 分子。疫苗將以預充式註射器的形式提供。我們相信，這將有助於推動藥劑師和醫生採用我們的一些 RSV 產品。

In oncology, for mRNA-4157 now called individualized neoantigen therapy, or INT, we are scaling up manufacturing to support clinical development and commercial markets. Our commercial team is also working to prioritize tumor types to select for additional Phase III studies in addition to melanoma and lung.

在腫瘤學領域，對於現在稱為個人化新抗原治療（INT）的 mRNA-4157，我們正在擴大生產規模以支持臨床開發和商業市場。我們的商業團隊也正在努力確定除黑色素瘤和肺癌之外的腫瘤類型的優先順序，以選擇進行其他 III 期研究。

Turning to the pipeline. At Vaccine Day, we discuss detailed data from our RSV vaccine that were presented at RSVVW medical meetings. We believe the profile of RSV vaccine is potentially best-in-class. We shared top line data on the 2 programs announcing the initiation of Phase 303, the Phase III study that we intend to use for accelerated approval as well as strategy for our next-generation Flu programs. We also announced the start of Phase III for next-gen COVID vaccine, mRNA-1283, which should be refrigerator-stable.

轉向管道。在疫苗日，我們討論了在 RSVVW 醫學會議上展示的 RSV 疫苗的詳細數據。我們相信 RSV 疫苗的特性可能是同類最佳的。我們分享了有關宣布啟動第 303 階段的兩個項目的頂線數據，第 303 階段研究是我們打算用於加速審批的第三階段研究，也是我們下一代流感項目的策略。我們也宣布啟動下一代 COVID 疫苗 mRNA-1283 的第三階段研究，該疫苗應具有冰箱穩定性。

Today, we're also announcing a new program for pandemic readiness for Influenza H5. In latent vaccine, our CMV Phase III trial continued progress and is greater than 50% enrolled. I'm also very pleased to announce progress in our early-stage program, EBV and HIV. EBV, as you know, has 2 programs. The EBV Phase I trials to prevent mononucleosis with mRNA-1189 are fully enrolled in adults and also in adolescents. Our EBV trial for the treatment of long-term complication for EBV infection has now started enrolling. And for HIV, we shall interim analysis from our Phase I study at Vaccines Day.

今天，我們也宣布了一項針對 H5 型流感大流行的應對新計畫。在潛伏性疫苗方面，我們的 CMV III 期試驗持續取得進展，參與人數已超過 50%。我也很高興地宣布我們的早期專案 EBV 和 HIV 取得了進展。如您所知，EBV 有 2 個程式。使用 mRNA-1189 預防單核細胞增多症的 EBV I 期試驗已在成人和青少年中全面招募。我們針對 EBV 感染長期併發症治療的 EBV 試驗現已開始招募患者。對於愛滋病毒，我們將在疫苗日對第一階段研究進行中期分析。

We also introduced new programs. We are working on vaccines for Norovirus and Lyme Disease. Lyme is the first bacterial pathogen we are targeting with mRNA platform (inaudible) vaccine. In Therapeutics, we participated in AACR meeting where we presented detailed Phase II data from our INT program partnered with Merck. Later on the call, Stephen will take you through the data presented there.

我們也推出了新的項目。我們正在研究諾羅病毒和萊姆病的疫苗。萊姆病是我們利用 mRNA 平台（聽不清楚）疫苗針對的第一個細菌病原體。在治療學方面，我們參加了 AACR 會議，在會上我們展示了與默克合作的 INT 計劃的詳細 II 期數據。稍後在通話中，Stephen 將向您介紹那裡呈現的數據。

Already this pipeline is also making progress. We're excited to announce a new milestone for our PA program. The Phase I/II trial in propionic acidemia or PA, is now in dose expansion phase. And additional data from this study will be presented at the American Society for Gene and Cell Therapy later this month in May.

這條管道目前也正在取得進展。我們很高興地宣布我們的 PA 計劃取得了新的里程碑。丙酸血症或 PA 的 I/II 期試驗目前處於劑量擴展階段。這項研究的更多數據將於本月稍晚在美國基因和細胞治療學會上發表。

The company continues to expand at a rapid pace. We have 47 programs underway which now reflects the inclusion of new program (inaudible) in the quarter and removes programs that are not continuing to develop. The full of these pipeline can be seen in the appendix of this presentation or obviously on our website. We now have more than 4,000 team members and 17 commercial subsidiaries across Americas, Europe and Asia Pacific.

公司繼續快速擴張。我們有 47 個項目正在進行中，這反映了本季新項目（聽不清楚）的納入，並刪除了不再繼續開發的項目。您可以在本簡報的附錄或我們的網站上查看這些管道的完整內容。我們目前擁有超過 4,000 名團隊成員和遍布美洲、歐洲和亞太地區的 17 個商業子公司。

In addition to our commercial subsidiaries, we also announced we're opening a Seattle office as a technology hub, where we're hiring the data scientists and engineers who will help digitize our business and expand our AI capabilities. I'm also happy to announce Moderna was officially recognized in March has a Great Place To Work by the Great Place To Work Institute. Our $16.4 billion of cash at the other quarter is enabling us to scale across our research, development, manufacturing, commercial and G&A.

除了我們的商業子公司外，我們還宣布將在西雅圖開設一個辦事處作為技術中心，在那裡我們將聘請資料科學家和工程師來幫助我們實現業務數位化並擴展我們的人工智慧能力。我也很高興地宣布，Moderna 公司於 3 月被卓越職場研究所正式評為卓越職場公司。我們在另一個季度擁有 164 億美元現金，這使我們能夠擴大研究、開發、製造、商業和一般及行政管理 (G&A) 領域的規模。

With that introduction, let me now turn to Stephen.

介紹完畢，現在請容許我向史蒂芬提問。

Thank you, Stephane. Good morning or good afternoon, everyone. Today, I'll review the clinical progress in R&D at Moderna in the first quarter and highlight select data from the past few months has been presented. The core of our respiratory portfolio is made up of vaccines against COVID-19, flu and RSV, which are either commercial or in Phase III. We're advancing second-generation vaccines, this includes our second-generation refrigerator stable COVID-19 vaccine candidate, mRNA-1283, which is rapidly enrolling in its Phase III study and 2 next-generation influenza vaccines that are in Phase II. We believe combination vaccines will be the future of our respiratory franchise. And we're pleased that we now have 5 different combination vaccine candidates in early clinical trials, including 2 specifically designed for pediatric populations.

謝謝你，史蒂芬。大家早安或下午好。今天，我將回顧 Moderna 第一季的臨床研發進展，並重點介紹過去幾個月的部分數據。我們的呼吸道產品組合的核心是針對 COVID-19、流感和呼吸道合胞病毒的疫苗，這些疫苗要么已經商業化，要么處於 III 期階段。我們正在推進第二代疫苗，其中包括我們的第二代冷藏穩定的 COVID-19 候選疫苗 mRNA-1283，該疫苗正在迅速招募 III 期研究對象，以及兩種處於 II 期研究的下一代流感疫苗。我們相信聯合疫苗將成為我們呼吸道疫苗特許經營的未來。我們很高興現在有 5 種不同的組合疫苗候選藥物處於早期臨床試驗階段，其中 2 種是專門為兒科族群設計的。

With 11 programs in clinical trials, including 4 in Phase III and covering 5 different respiratory viruses, we believe this represents the broadest and most advanced portfolio of respiratory virus vaccine candidates. Now turning specifically to COVID.

目前有 11 個項目處於臨床試驗階段，其中 4 個處於 III 期臨床試驗階段，涵蓋 5 種不同的呼吸道病毒，我們相信這代表了最廣泛、最先進的呼吸道病毒候選疫苗組合。現在具體談談 COVID。

The FDA recently provided updates on several fronts. Our Omicron-targeting bivalent COVID-19 vaccine targeting the original and BA.4/5 strains is now our only authorized formulation in the United States with a simplified and streamlined regimen for both children and adults. Individuals, 65 years of age and those with certain kinds of immunocompromise are now also eligible to receive additional doses as needed or recommended by their physicians.

FDA 最近在多個方面提供了最新消息。我們的針對原始和 BA.4/5 株的 Omicron 靶向二價 COVID-19 疫苗目前是我們在美國唯一授權的配方，為兒童和成人提供簡化和精簡的治療方案。 65 歲及以上人士以及患有某些免疫功能低下的人現在也有資格根據需要或醫生的建議接受額外劑量。

As we look to the fall, the strain selection for an updated composition for fall 2023 boosters is now expected to come at the June 15 VRBPAC meeting. Moving to RSV.

展望秋季，預計 2023 年秋季加強劑更新組合的菌株選擇將在 6 月 15 日的 VRBPAC 會議上進行。移至 RSV。

We're pleased by the profile of our vaccine in older adults with high and consistent efficacy against RSV lower respiratory tract disease across populations in our large Phase III study. At 2 recent medical meetings, we've shared data showing our vaccine's efficacy was consistently high across all age groups, including in the oldest adult and in participants with preexisting comorbidities that put them at higher risk.

我們很高興看到，在我們大規模的 III 期研究中，我們的疫苗對老年族群的呼吸道合胞病毒下呼吸道疾病具有高效且一致的療效。在最近的兩次醫學會議上，我們分享了數據，顯示我們的疫苗在所有年齡層中都具有較高的有效性，包括最年長的成年人和合併症而面臨更高風險的參與者。

mRNA-1345 has also shown a favorable tolerability profile with AEs mostly grade 1 or grade 2, mild to moderate. As we shared during Vaccines Day, today, we have not seen any cases of Guillain-Barré syndrome or other severe demyelinating events in the trial.

mRNA-1345 也表現出良好的耐受性，不良事件大多為 1 級或 2 級，輕度至中度。正如我們在疫苗日今天所分享的那樣，我們在試驗中沒有看到任何格林巴利症候群或其他嚴重脫髓鞘事件的病例。

Moving to flu. Our Phase III efficacy study in the Northern Hemisphere, P302 is ongoing. And last month, we announced that the study did not accrue sufficient cases to declare early success at the interim analysis and that the DSMB recommended that we continue the study. That trial is still accruing cases through the end of this flu season with an update expected this summer.

轉向流感。我們在北半球進行的 III 期療效研究 P302 正在進行中。上個月，我們宣布該研究沒有累積足夠的病例來宣布中期分析取得早期成功，而 DSMB 建議我們繼續這項研究。到本流感季節結束時，試驗仍在累積病例，預計今年夏天會有更新。

The preliminary immunogenicity data from that P302 study showed that HAI neutralizing titers were consistent with superiority for both A strains and non-inferior immunogenicity for the B strains when compared to the licensed flu vaccine. Now I'm pleased to announce that we've initiated our Phase III P303 flu study with an updated formulation of mRNA-1010. P303 is testing an update that is designed to increase the HAI neutralizing titers against the B antigens. This is an immunogenicity study and is expected to enroll approximately 2,400 adults this spring. We believe this study will support our initial flu filing and the potential for a 2024 launch if approved by regulators.

P302 研究的初步免疫原性數據顯示，與已獲許可的流感疫苗相比，HAI 中和滴度對 A 型株均具有優勢，對 B 型株具有非劣效免疫原性。現在我很高興地宣布，我們已經啟動了第三階段 P303 流感研究，並採用了更新的 mRNA-1010 配方。 P303 正在測試一項更新，旨在增加針對 B 抗原的 HAI 中和滴度。這是一項免疫原性研究，預計今年春季將招募約 2,400 名成年人。我們相信，這項研究將支持我們最初的流感申請，如果獲得監管機構的批准，有可能在 2024 年推出。

Now turning to our latent vaccines. Our CMV vaccine Phase III study in women and childbearing age is ongoing and has enrolled more than 50% of participants. We also have an ongoing Phase I/II adolescent dose-ranging study with this vaccine that will expand potential eligible populations. As Stephane mentioned earlier, we continue to make significant progress against all of our latent vaccines in earlier-stage clinical trials, including candidates against EBV, HIV and VZV. As Stephane mentioned, our EBV vaccine includes 2 vaccine candidates, our EBV program includes 2 vaccine candidates mRNA-1189 and mRNA-1195 and are in clinical trials for prevention of infectious mononucleosis and for the prevention of longer-term sequelae of EBV infection respectively.

現在來談談我們的潛在疫苗。我們針對育齡婦女的CMV疫苗III期研究正在進行中，已招募超過50%的參與者。我們也正在進行該疫苗的 I/II 期青少年劑量範圍研究，這將擴大潛在的合格族群。正如 Stephane 先前提到的，我們在早期臨床試驗中針對所有潛在疫苗持續取得重大進展，包括針對 EBV、HIV 和 VZV 的候選疫苗。正如 Stephane 所提到的，我們的 EBV 疫苗包括 2 種候選疫苗，我們的 EBV 計畫包括 2 種候選疫苗 mRNA-1189 和 mRNA-1195，分別用於預防傳染性單核細胞增多症和預防 EBV 感染的長期後遺症的臨床試驗。

Now at Vaccines Day, we are pleased to share interim results of our HIV vaccine, mRNA-1644, which continues to advance. Our pipeline in therapeutics targets unmet needs across immuno-oncology, rare disease, cardiovascular disease and autoimmune diseases. All the trials in these therapeutic areas are ongoing. And today, I'll highlight a few of the recent updates.

如今正值疫苗日，我們很高興分享我們的愛滋病毒疫苗 mRNA-1644 的中期結果，該疫苗正在繼續取得進展。我們的治療藥物管線針對免疫腫瘤學、罕見疾病、心血管疾病和自體免疫疾病領域未滿足的需求。這些治療領域的所有試驗仍在進行中。今天，我將重點介紹一些最近的更新。

On Slide 16, are the data shared at AACR from our Phase II study in adjuvant melanoma with a combination of our individualized neoantigen therapy plus KEYTRUDA versus KEYTRUDA alone. The Kaplan-Meier curve for relapse-free survival solution here. Overall, there was a 44% reduction in the rate of relapse or death with a combination of INT and KEYTRUDA compared to KEYTRUDA alone. We are encouraged by the continued separation of the 2 curves with a follow-up at 18 months. Note that there are very few participants beyond the 140 week cutoff at the right of this slide, less than 10 participants in total. Thus, as the data continues to mature, with additional follow-up time, we remain cautiously optimistic that this picture will get even better.

投影片 16 是我們在 AACR 上分享的輔助黑色素瘤 II 期研究的數據，該研究結合了我們的個人化新抗原療法和 KEYTRUDA 與單獨使用 KEYTRUDA。這裡是無復發生存解決方案的 Kaplan-Meier 曲線。整體而言，與單獨使用 KEYTRUDA 相比，INT 和 KEYTRUDA 合併使用可將復發率或死亡率降低 44%。我們對 18 個月的追蹤中兩條曲線的持續分離感到鼓舞。請注意，此投影片右側 140 週截止時間之後的參與者非常少，總共不到 10 名參與者。因此，隨著數據的不斷成熟和後續時間的增加，我們仍然謹慎樂觀地認為，情況會變得更好。

Now on Slide 17, I want to briefly highlight some of the additional data that was shared at AACR. The subgroup analysis confirm the strength of the treatment effect across 2 important markers that are known to predict responses to KEYTRUDA. Again, on this slide, we're looking at the relapse-free survival.

現在在第 17 張投影片上，我想簡單介紹 AACR 分享的一些附加資料。亞組分析透過已知可預測 KEYTRUDA 反應的 2 個重要標記物證實了治療效果的強度。再次，在這張投影片上，我們正​​在研究無復發生存率。

On the left side, the results are stratified by high tumor mutational burden in red and low tumor mutational burden in blue. In each case, the solid lines are for the INT combination and the dash line is for KEYTRUDA monotherapy control. If you start by looking and comparing the control arms for KEYTRUDA, you will note that the TMB high participants, the red dash line, have a higher relapse-free survival than the TMB low participants in the blue dash line. This is expected because of what we know about KEYTRUDA, and shows that the controls are performing as we expect.

在左側，結果按高腫瘤突變負擔（紅色）和低腫瘤突變負擔（藍色）分層。在每種情況下，實線代表 INT 組合，虛線代表 KEYTRUDA 單藥療法控制。如果您先查看並比較 KEYTRUDA 的對照組，您會注意到 TMB 高參與者（紅色虛線）的無復發生存期比 TMB 低參與者（藍色虛線）更高。這是預料之中的，因為我們對 KEYTRUDA 有所了解，並且表明控制措施的執行情況符合我們的預期。

Now moving to the INT combination arms, the solid lines and comparing them against the dotted lines of the same color, you can clearly see that the INT combination led to higher relapse-free survival for both TMB high and TMB low patients. This highlights the robustness of the response for INT. It's also quite exciting to note that the improved response rate seen in the blue TMB low population, which historically does not respond well -- as well to KEYTRUDA.

現在轉到 INT 組合組，將實線與相同顏色的虛線進行比較，您可以清楚地看到，INT 組合為 TMB 高和 TMB 低患者帶來了更高的無復發生存期。這凸顯了 INT 響應的穩健性。值得注意的是，藍色 TMB 低族群的反應率有所提高，而歷史上該族群對 KEYTRUDA 的反應並不好。

On the right, you'll see the result as stratified by PD-L1 status. Now as with the TMB analysis, PD-L1 is known to predict response rates to immunotherapy. As you can see by the dashed lines for KEYTRUDA monotherapy control groups, the relapse-free survival curves look better for PD-L1 positive tumors, these are the red dash lines, and worse for patients unfortunate enough have PD-L1 negative tumors, the blue dashed lines. This isn't surprising as KEYTRUDA monotherapy acts by blocking the PD-1, PD-L1 access.

在右側，您將看到按 PD-L1 狀態分層的結果。現在，與 TMB 分析一樣，PD-L1 可以預測免疫療法的反應率。從 KEYTRUDA 單藥治療對照組的虛線可以看出，PD-L1 陽性腫瘤的無復發生存曲線表現較好，即紅色虛線，而對於不幸患有 PD-L1 陰性腫瘤的患者來說，無復發生存曲線表現較差，即藍色虛線。這並不奇怪，因為 KEYTRUDA 單一療法透過阻斷 PD-1、PD-L1 通道發揮作用。

As with TMB on the left, the solid lines on the RFS curves for the combination show the combination of INT, red denotes PD-L1 positive and blue denotes PD-L1 negative. In both cases, there is an increase in the rate of relapse-free survival with the combination treatment. It is encouraging to note again that the response rates are significantly improved for the PD-L1 negative patients. Indeed, the hazard ratio in this subgroup analysis is 0.162.

與左側的 TMB 一樣，組合的 RFS 曲線上的實線顯示 INT 的組合，紅色表示 PD-L1 陽性，藍色表示 PD-L1 陰性。在這兩種情況下，聯合治療都能提高無復發生存率。令人鼓舞的是，PD-L1 陰性患者的反應率顯著提高。事實上，該亞組分析的風險比為 0.162。

Now pulling back, these data highlights that the observed improvement in relapse-free survival seen in the initial analysis of our Phase II study looks broad-based across subgroups with an indication of a potentially important benefit even in patients who have higher risk of progression, whether due to PD-L1 status or tumor mutational burden compared to KEYTRUDA monotherapy alone.

現在回顧一下，這些數據突出表明，在我們 II 期研究的初步分析中觀察到的無復發生存期的改善在各個亞組中都是廣泛的，這表明即使對於進展風險較高的患者，無論是由於 PD-L1 狀態還是腫瘤突變負擔，與單獨使用 KEYTRUDA 單藥治療相比，也可能具有重要的益處。

Now these positive data are just the beginning for this ongoing study. We'll be sharing additional data from the Phase II study at ASCO, including distant metastasis-free survival which was a secondary endpoint in the primary analysis just conducted, and the same data cuts that I just shared. We'll also be sharing important additional biomarker data. In addition, to this protocol calls for subsequent analysis at 51 events, which is when we will also be updating the Kaplan-Meier curves for relapse-free survival with longer follow-up time across the full population, and we eagerly await those updates.

現在這些積極的數據只是這項正在進行的研究的開始。我們將分享更多來自 ASCO 的 II 期研究的數據，包括遠處無轉移生存期（這是剛剛進行的主要分析中的次要終點），以及我剛剛分享的相同數據片段。我們還將分享重要的附加生物標記數據。此外，該方案要求對 51 個事件進行後續分析，屆時我們還將更新 Kaplan-Meier 曲線，以便在整個人群中進行更長的追蹤時間，我們熱切期待這些更新。

INT has received breakthrough therapy in the United States and PRIME designation in Europe, which will facilitate frequent dialogue with regulators, as we work to quickly advance this treatment for patients. As Stephane mentioned earlier, we plan to initiate our Phase III study in adjuvant melanoma in 2023 and rapidly expand to additional tumor types, including non-small cell lung cancer. We're working closely with our partner, Merck, to explore additional opportunities within KEYTRUDA approved indications and beyond that label. And finally, a quick update on our propionic acidemia program.

INT 已在美國獲得突破性療法認定，並在歐洲獲得 PRIME 認定，這將有助於我們與監管機構進行頻繁對話，以便我們能夠快速為患者推進這種治療。正如 Stephane 先前提到的，我們計劃在 2023 年啟動輔助黑色素瘤的 III 期研究，並迅速擴展到其他腫瘤類型，包括非小細胞肺癌。我們正與我們的合作夥伴默克公司密切合作，探索 KEYTRUDA 批准適應症範圍內及該標籤之外的更多機會。最後，快速更新一下我們的丙酸血症計劃。

Our Phase I/II study is ongoing and currently enrolling patients in the 0.9 milligrams per kilogram cohort. We have identified a dose for expansion and have moved into that expansion arm in the study. I'm pleased to announce just yesterday that a clinical update through the earlier -- time point earlier this year, including an update on safety and the rate of major metabolic decompensation from the higher dose cohorts and including longer-term follow-up from the lower dose cohorts will now be presented at the American Society of Gene and Cell Therapy Meeting on May 18. The abstract for that presentation is now available and can be found in the link on this slide. We look forward to sharing a lot more about the progress of this medicine and our other rare disease programs in the months ahead.

我們的 I/II 期研究正在進行中，目前正在招募每公斤 0.9 毫克的患者。我們已經確定了擴展劑量，並已進入研究中的擴展部分。我很高興地宣布，昨天將在 5 月 18 日的美國基因和細胞治療學會會議上公佈今年早些時候的臨床更新結果，其中包括安全性更新和高劑量組的主要代謝失代償率，以及低劑量組的長期隨訪結果。該報告的摘要現已發布，可在本投影片的連結中找到。我們期待在未來幾個月分享更多有關這種藥物和我們其他罕見疾病項目的進展。

With that, I'll turn the call over to Arpa.

說完這些，我將把電話轉給 Arpa。

Thank you, Stephen, and good day to everyone. I will first start with a review of sales in the quarter. On Slide 22, we summarized the composition of our sales in the first quarter. As you'll see on the chart, our sales to Europe were $0.6 billion and sales to the rest of the world were $1.3 billion. Approximately $1.8 billion of sales from previously announced APAs were delivered in the first quarter of 2023, representing the vast majority of the $2 billion expected in the first half of 2023.

謝謝你，史蒂芬，祝大家有美好的一天。我將首先回顧本季的銷售情況。在投影片 22 上，我們總結了第一季的銷售組成。正如您在圖表上看到的，我們對歐洲的銷售額為 6 億美元，對世界其他地區的銷售額為 13 億美元。先前宣布的 APA 銷售額約 18 億美元於 2023 年第一季實現，佔 2023 年上半年預計銷售額 20 億美元的絕大部分。

As a reminder, U.S. sales for COVID vaccines are expected to begin in the second half of 2023, with updated strain-matched vaccine. Now as we turn to Slide 23, looking at the 2023 COVID deliveries, Today, we are reiterating a minimum of approximately $5 billion in COVID vaccine deliveries from current advanced purchase agreements. And we continue to expect additional orders from key markets. Of the $5 billion in 2023 deliveries from previously announced APAs, $2 billion, as I mentioned earlier, are expected to be delivered in the first half of 2023. We have already delivered $1.8 billion of that $2 billion in the first quarter with substantial fulfillment to Japan and the European Union. We expect to deliver the remaining approximately $3 billion in previously announced APAs in the second half of this year. Additionally, we expect new sales in the U.S., Japan, European Union, Asia and Latin America. I'm happy to announce that the commercial team has signed a contract with the Australian Government for 2023.

提醒一下，美國預計將於 2023 年下半年開始銷售 COVID 疫苗，並推出更新的病毒株配對疫苗。現在我們翻到第 23 張投影片，看看 2023 年的 COVID 交付情況，今天，我們重申，根據目前的預購協議，COVID 疫苗交付量至少約為 50 億美元。我們將繼續期待來自主要市場的更多訂單。在先前宣布的 2023 年交付的 50 億美元 APA 中，正如我之前提到的，預計將在 2023 年上半年交付 20 億美元。我們已經在第一季交付了其中的 18 億美元，其中大部分交付給了日本和歐盟。我們預計將在今年下半年交付之前宣布的剩餘約 30 億美元 APA。此外，我們預計美國、日本、歐盟、亞洲和拉丁美洲的銷售也將有所成長。我很高興地宣布，商業團隊已經與澳洲政府簽署了2023年的合約。

Our discussion with commercial buyers in the U.S. are positive, and I will elaborate on that shortly. In our discussions with commercial customers in the U.S. It is clear that our customers are aware that COVID is still a substantial health burden. Throughout 2022, COVID continued to be a leading cause of hospitalizations. Data available through September 2022, list COVID as the third leading cost of death in the U.S. only after heart disease and cancer, as shown in the first chart on the left. The chart on the right-hand side of the slide shows the most recent data available for U.S. hospitalizations for COVID, flu and RSV. As you'll see, with current season hospitalizations of over 600,000 per COVID, the hospitalization rate for COVID is almost triple that of flu as well as more than triple that of RSV. There continues to be a clear need to protect against severe COVID infections and our customers recognize that need.

我們與美國商業買家的討論是積極的，我很快就會詳細說明。在與美國商業客戶的討論中，我們清楚地認識到，我們的客戶意識到 COVID 仍然是一個巨大的健康負擔。在整個 2022 年，COVID 仍然是住院的主要原因。截至 2022 年 9 月的數據顯示，COVID 是美國僅次於心臟病和癌症的第三大死亡成本，如左側第一張圖表所示。幻燈片右側的圖表顯示了美國因 COVID、流感和呼吸道合胞病毒住院的最新數據。如您所見，本季度每例 COVID 住院人數超過 60 萬人，COVID 的住院率幾乎是流感的三倍，也是 RSV 的三倍多。顯然，預防嚴重的 COVID 感染的必要性仍然很大，我們的客戶也意識到了這種必要性。

For fall of 2023, we expect the U.S. market volume to be approximately 100 million doses. As we highlighted earlier in the year, the successful transition of our U.S. COVID business from a government driven to a commercial-driven model is critical. We have made great progress on this front, executing on our action plan to rapidly develop this commercial market. Importantly, the commercial team is in active discussions with customers throughout the U.S. We are contracting with national and regional pharmacies, integrated delivery networks, government health providers, including the VA, the CDC and the Department of Defense, for purchasing, organizations and other providers.

到 2023 年秋季，我們預計美國市場銷量將達到約 1 億劑。正如我們今年稍早強調的那樣，我們的美國 COVID 業務從政府驅動模式成功過渡到商業驅動模式至關重要。我們在這方面取得了很大進展，並正在執行我們的行動計劃以快速開發這個商業市場。重要的是，商業團隊正在與美國各地的客戶進行積極討論。我們正在與國家和地區藥局、綜合配送網路、政府醫療服務提供者（包括退伍軍人事務部、疾病預防控制中心和國防部）簽訂採購合約、組織和其他提供者。

In addition, our established national distribution infrastructure and our Moderna Direct e-commerce site is fully operational. Our global supply chain is in place to handle all U.S. customer needs including prefilled syringes and single-dose vials at the time of launch. I'm excited to share some of the launch preparation activities for the updated COVID-19 vaccine for fall vaccination campaigns. We believe these activities will drive consumers to get vaccinated.

此外，我們已建立的全國分銷基礎設施和 Moderna Direct 電子商務網站已全面投入營運。我們的全球供應鏈可以滿足所有美國客戶的需求，包括產品推出時的預充式註射器和單劑量小瓶。我很高興與大家分享秋季疫苗接種活動更新版 COVID-19 疫苗的一些啟動準備活動。我們相信這些活動將推動消費者接種疫苗。

First, we are taking an omnichannel approach via tailored digital messaging to healthcare providers. This multifaceted approach will allow us to drive broad awareness and continue to emphasize the ongoing need for COVID production. Later this year, we will be disseminating customized content to drive physician demand across immunizing physicians, institutional decision-makers, as well as influencers.

首先，我們採取全通路方式，透過為醫療保健提供者提供客製化的數位資訊。這種多管齊下的方法將使我們能夠提高廣泛的認識，並繼續強調對 COVID 生產的持續需求。今年晚些時候，我們將傳播客製化內容，以推動免疫醫生、機構決策者以及影響者的需求。

We are also partnering with our customer base across the different commercial segments to assist with their fall immunization programs. We believe there's an opportunity to continue to provide education, both to staff as well as to patients. And we believe there is an opportunity to harmonize and simplify the vaccination process for patients who are going in to skip their flu vaccine.

我們也與不同商業領域的客戶群合作，協助他們進行秋季免疫計畫。我們相信有機會繼續為員工和患者提供教育。我們相信，對於不想接種流感疫苗的患者來說，有機會協調和簡化疫苗接種流程。

Consumer promotion will be focused primarily in the fall of this year, driving patients to seek Moderna's COVID vaccine through significant DTC efforts. As I mentioned earlier, we are looking to simplify the experience for our consumers who are already going in together seasonal influenza vaccine this fall. We are energized for this fall season.

消費者推廣將主要集中在今年秋季，透過大力 DTC 努力推動患者尋求 Moderna 的新冠疫苗。正如我之前提到的，我們希望簡化今年秋天已開始接種季節性流感疫苗的消費者的體驗。我們為這個秋天注入了活力。

Moving on to Slide 27. I will update you on our second near-term commercial opportunity, which is RSV. We are excited for the expected 2024 launch of our RSV vaccine and the commercial team is undertaking a number of activities to ensure that we develop what we hope will be a large share of that market as quickly as possible. We are already raising awareness of the health and economic burden of RSV by generating and presenting detailed data from our Phase III study at major medical meetings.

轉到投影片 27。我將向您介紹我們的第二個近期商業機會，即 RSV。我們對預計於 2024 年推出的 RSV 疫苗感到非常興奮，商業團隊正在進行一系列活動，以確保我們盡快開發出我們希望佔據該市場很大份額的產品。透過在主要醫學會議上產生和展示我們第三階段研究的詳細數據，我們已經提高了人們對呼吸道合胞病毒對健康和經濟負擔的認識。

Our medical team has shared additional data showing that vaccine efficacy is consistently high across all tested age groups as well as in participants with preexisting comorbidities. The figures on the right-hand side of the slide, detail efficacy data in these important subgroups. As we share these data at medical congresses, we are encouraged by payer and key opinion leader feedback on our data and the application of our mRNA platform to prevent RSV.

我們的醫療團隊分享了額外的數據，顯示疫苗在所有接受測試的年齡層以及患有合併症的參與者中都具有持續較高的有效性。投影片右側的圖表詳細說明了這些重要亞組的療效數據。當我們在醫學大會上分享這些數據時，付款人和關鍵意見領袖對我們的數據以及使用 mRNA 平台預防 RSV 的回饋讓我們備受鼓舞。

We're engaging with payers and NITAG to ensure access upon launch. And the commercial team is active in local markets preparing for a commercial launch in 2024. Specifically, we are building our digital capabilities so that we will be able to efficiently educate customers as soon as the vaccine is approved. And as we invest in prelaunch activities, we have already begun manufacturing components of the vaccine and prefilled syringes. We are excited about the profile of the products we will be launching into these large respiratory markets.

我們正在與付款人和 NITAG 合作，以確保發佈時即可存取。商業團隊正在積極開展當地市場工作，為 2024 年的商業發布做準備。具體來說，我們正在建立數位化能力，以便能夠在疫苗獲得批准後立即有效地教育客戶。隨著我們對上市前活動的投資，我們已經開始生產疫苗和預充式註射器的組件。我們對即將向這些大型呼吸市場推出的產品感到非常興奮。

As we discussed at Vaccines Day, the estimated total addressable markets for our 3 key respiratory vaccines are substantial. With COVID, RSV and flu offering potential addressable markets of $15 billion, $6 billion to $8 billion and $6 billion to $9 billion, respectively. We believe we can take a sizable share of this roughly $30 billion respiratory market.

正如我們在疫苗日所討論的那樣，我們三種主要呼吸道疫苗的預期總目標市場規模巨大。 COVID、RSV 和流感分別提供了 150 億美元、60 億至 80 億美元和 60 億至 90 億美元的潛在目標市場。我們相信，我們可以在這個約 300 億美元的呼吸市場中佔據相當大的份額。

The commercial team is well underway in preparing for RSV and flu launches in 2024. We believe our opportunity in the respiratory market will continue to expand beyond 2024 with our next-gen vaccines and importantly, with future combination vaccines, positioning us to drive share over time.

商業團隊正在為 2024 年推出呼吸道合胞病毒和流感疫苗做準備。我們相信，憑藉我們的下一代疫苗以及重要的未來聯合疫苗，我們在呼吸道市場的機會將在 2024 年以後繼續擴大，這將使我們能夠隨著時間的推移提高市場份額。

Now on to Slide 29, I want to share with you how the commercial team is helping identify eligible patient populations in the adjuvant and neoadjuvant settings for various tumor types. Along with our partner, Merck, we have already announced that we will start Phase III trials in Adjuvant melanoma and adjuvant non-small cell lung cancer. There is an annual population of over 130,000 new patients in the U.S. and Europe in these 2 indications.

現在轉到投影片 29，我想與大家分享商業團隊如何幫助確定各種腫瘤類型的輔助和新輔助治療中符合條件的患者群體。我們與合作夥伴默克公司已經宣布，我們將啟動輔助黑色素瘤和輔助非小細胞肺癌的 III 期試驗。美國和歐洲每年因這兩種疾病新增患者人數超過 13 萬人。

Patient populations for additional potential adjuvant and neoadjuvant tumor types are listed on the right-hand side. Our commercial teams are working closely with our clinical teams to identify the largest unmet need for addressable tumor types for individualized neoantigen therapy. We are excited to be launching into a space where we have one medicine for one patient in areas of great unmet need in cancer. Given the individualized approach, we are reimagining our commercial model, along with our partner, along with patient care journey, end-to-end.

右側列出了其他潛在輔助和新輔助腫瘤類型的患者群體。我們的商業團隊正在與臨床團隊密切合作，以確定個人化新抗原治療中可解決腫瘤類型的最大未滿足需求。我們很高興能夠進入這樣一個領域：在癌症治療領域中，我們為每位患者提供一種藥物，以滿足尚未滿足的巨大需求。鑑於個性化的方法，我們正在與合作夥伴一起重新構想我們的商業模式以及端到端的患者護理旅程。

With that, I will turn it over to Jamey.

說完這些，我將把麥克風交給 Jamey。

Thanks, Arpa, and hello, everyone. This morning, I will cover our Q1 financial performance, review the framework for our 2023 financial outlook and provide a quick recap from our recent Vaccines Day presentation. Moving to our first quarter results, starting on Slide 31.

謝謝，Arpa，大家好。今天上午，我將介紹我們第一季的財務業績，回顧我們 2023 年財務展望的框架，並簡要回顧我們最近的疫苗日演示。從第 31 張投影片開始，介紹我們的第一季業績。

Total product sales decreased 69% year-over-year to $1.8 billion, the decrease in 2023 is consistent with our expectations and mainly driven by lower sales volume compared to the prior year. Cost of sales for the first quarter of 2023 was $792 million, in addition to our unit-driven manufacturing costs, this includes royalties of $86 million and the following charges: $148 million for inventory write-downs related to excess and obsolete COVID-19 products, unutilized manufacturing capacity of $135 million and losses on firm purchase commitments and related cancellation fees of $95 million. These charges, other than royalties, were driven by costs associated with surplus production capacity and an overall lower demand forecast primarily from lower-income countries.

總產品銷售額年減 69% 至 18 億美元，2023 年的降幅與我們的預期一致，主要原因是銷售量較前一年下降。 2023 年第一季的銷售成本為 7.92 億美元，除了單位驅動的製造成本外，還包括 8,600 萬美元的特許權使用費和以下費用：與過剩和過時的 COVID-19 產品相關的庫存減記 1.48 億美元、未使用的製造能力 1.35 億美元以及確定購買費用和取消相關的 950 萬美元以及取消相關費用。除特許權使用費外，這些費用是由過剩生產能力相關的成本以及主要來自低收入國家的整體需求下降預測所驅動。

Cost of sales as a percent of product sales was 43% compared to 17% in Q1 2022. The increase was driven by the aforementioned charges over lower product sales compared to the prior year and higher manufacturing costs as we switch to smaller dose vials as well as lower product sales to absorb fixed manufacturing costs.

銷售成本佔產品銷售額的百分比為 43%，而 2022 年第一季為 17%。成長是由於上述費用導致的，這些費用與上年相比產品銷售額下降，以及由於我們改用較小劑量的小瓶而導致製造成本上升，以及產品銷售額下降以吸收固定製造成本。

Research and development expenses were $1.1 billion, which increased by 104% versus the prior year. The increase in R&D spend continues to be driven by clinical trial-related expenses particularly with our Phase III studies for RSV, seasonal flu and CMV. The increase in R&D was also attributable to increases in personnel-related costs due to increased headcount and our recently announced collaboration agreements with Life Edit and Generation Bio.

研發費用為11億美元，較上年成長104%。研發支出的成長持續受到臨床試驗相關費用的推動，特別是我們針對呼吸道合胞病毒、季節性流感和鉅細胞病毒的 III 期研究。研發費用的增加也歸因於員工人數增加導致的人員相關成本的增加以及我們最近宣布的與 Life Edit 和 Generation Bio 的合作協議。

SG&A expenses were $305 million, reflecting an increase of 14% year-over-year. The growth in spending was primarily driven by continued investments in personnel and outside services in support of our marketed products and related commercialization activities as well as our company expansion.

銷售、一般及行政費用為 3.05 億美元，較去年同期成長 14%。支出的成長主要得益於對人員和外部服務的持續投資，以支持我們行銷的產品和相關商業化活動以及公司擴張。

Income tax provision was a net benefit of $384 million for the first quarter, driven by our full year outlook, which includes international provisions, R&D credits and nonrecurring items. Net income was $79 million compared to a net income of $3.7 billion last year. Diluted earnings per share was $0.19 compared to a diluted earnings per share of $8.58 in Q1 2022.

第一季所得稅準備金淨收益為 3.84 億美元，這得益於我們對全年的展望，其中包括國際準備金、研發信貸和非經常性項目。淨收入為 7,900 萬美元，而去年的淨收入為 37 億美元。每股攤薄收益為 0.19 美元，而 2022 年第一季每股攤薄收益為 8.58 美元。

We ended Q1 with cash and investments of $16.4 billion compared to $18.2 billion at the end of the fourth quarter of 2022. The decrease was driven by a reduction of cash deposits as we delivered products against prepayments and our share buyback activity. Cash deposits for future product supply declined from $2.6 billion at the end of 2022 to $1.8 billion by the end of Q1 2023, in line with our expectations.

我們第一季末的現金和投資為 164 億美元，而 2022 年第四季末為 182 億美元。下降的原因是，我們根據預付款交付產品以及我們的股票回購活動導致現金存款減少。未來產品供應的現金存款從 2022 年底的 26 億美元下降到 2023 年第一季末的 18 億美元，符合我們的預期。

Now turning to Slide 33. I want to give an update on the progress we have made on our capital allocation priorities. Our top investment priority has been and will continue to be reinvesting in the base business across multiple areas. As mentioned earlier, R&D spending in the first quarter increased 104% year-over-year, and we continue to project R&D investments of approximately $4.5 billion for the full year of 2023.

現在翻到第 33 張投影片。我想介紹一下我們在資本配置重點上的進展。我們的首要投資重點一直是並將繼續是對多個領域的基礎業務進行再投資。如前所述，第一季的研發支出年增 104%，我們繼續預測 2023 年全年的研發投資約為 45 億美元。

As discussed at our Vaccines Day presentation, the majority of this investment is for our respiratory vaccine franchise, which we expect to generate significant returns in the relatively near term. We are also investing in our digital capabilities. the commercial build-out of the organization as well as expanding our manufacturing footprint. We plan to significantly accelerate our capital expenditures in 2023 as we expand both our international and U.S. manufacturing footprint.

正如我們在疫苗日演講中所討論的那樣，這項投資的大部分用於我們的呼吸道疫苗特許經營，我們預計該特許經營將在相對較短的時間內產生可觀的回報。我們也在投資我們的數位化能力。組織的商業建設以及擴大我們的製造足跡。隨著我們擴大國際和美國製造業務，我們計劃在 2023 年大幅加快資本支出。

Our second investment priority is to seek attractive external investments and collaboration opportunities that will enable and complement our platform. As previously announced, we successfully closed our acquisition of OriCiro in the first quarter and the integration of the operations are well underway. Additionally, we entered into 2 collaboration agreements during the quarter with Life Edit and Generation Bio. We are in multiple active discussions regarding additional external collaboration opportunities, and we'll continue to be disciplined in our approach.

我們的第二個投資重點是尋求有吸引力的外部投資和合作機會，以支持和補充我們的平台。正如先前宣布的，我們在第一季成功完成對 OriCiro 的收購，目前業務整合正在順利進行。此外，我們在本季與 Life Edit 和 Generation Bio 簽訂了兩項合作協議。我們正在就額外的外部合作機會進行多次積極討論，並且我們將繼續嚴格遵守我們的方法。

After evaluating internal and external investment opportunities, we then assess additional uses of cash. In the first quarter of 2023, we repurchased 3.6 million shares for $526 million. We had $2.3 billion of share repurchase authorization remaining as of March 31, 2023.

在評估內部和外部投資機會之後，我們評估現金的其他用途。 2023 年第一季度，我們以 5.26 億美元回購了 360 萬股。截至 2023 年 3 月 31 日，我們剩餘的股票回購授權額為 23 億美元。

Now let's turn to our updated 2023 financial framework on Slide 34. We continue to have advanced purchase agreements for COVID vaccine sales of approximately $5 billion for delivery in 2023. And we are in active negotiations for commercial market and government contracts in the U.S. and additional contracts for Japan, the EU and other key markets. We continue to expect first half sales to be approximately $2 billion.

現在讓我們轉到投影片 34 上更新的 2023 年財務框架。我們繼續簽訂了約 50 億美元的 COVID 疫苗預購協議，將於 2023 年交付。我們正在積極談判美國商業市場和政府合同，以及日本、歐盟和其他主要市場的額外合約。我們仍預計上半年銷售額約為 20 億美元。

Due to the seasonal nature of our respiratory business, we expect sales in Q2 of $0.2 billion to $0.3 billion. We continue to expect fiscal year 2023 reported cost of sales to be 35% to 40% of sales which includes 5% royalties. For Q2, we expect cost of sales between $0.5 billion and $0.6 billion. Due to the seasonal nature of our business, we expect our cost of sales in the first half of the year could be above the range of 35% to 40% and then reduce our average through the second half of the year.

由於呼吸業務的季節性，我們預計第二季的銷售額為 2 億至 3 億美元。我們繼續預期 2023 財年的銷售成本將佔銷售額的 35% 至 40%，其中包括 5% 的特許權使用費。對於第二季度，我們預計銷售成本在 5 億美元至 6 億美元之間。由於我們業務的季節性，我們預計上半年的銷售成本可能會高於 35% 至 40% 的範圍，然後在下半年降低平均值。

For R&D and SG&A, we continue to expect full year expenses to be approximately $6 billion, with approximately $4.5 billion in research and development. We now anticipate a full year tax benefit of $0.3 billion to $0.5 billion, driven by R&D credits, international provisions and nonrecurring items. And finally, we continue to expect capital expenditures of approximately $1 billion.

對於研發和銷售、一般及行政費用，我們繼續預計全年支出約為 60 億美元，其中研發支出約為 45 億美元。我們現在預計全年稅收優惠將達到 3 億美元至 5 億美元，主要得益於研發抵免、國際撥備和非經常性項目。最後，我們繼續預期資本支出約為 10 億美元。

Before I turn the call back to Stephane, for those who weren't able to attend or haven't seen the webcast from our Vaccines Day presentation, I wanted to quickly recap the financial takeaways. Given the current significant investment in our respiratory franchise, we wanted to lay out the potential return we envision by the year 2027 for this franchise.

在我將電話轉回給史蒂芬之前，對於那些無法參加或沒有觀看我們疫苗日演講網絡直播的人，我想快速回顧一下財務要點。鑑於我們目前對呼吸系統特許經營權的大量投資，我們希望列出到 2027 年我們預計該特許經營權的潛在回報。

Picking up where Arpa ended her earlier remarks, we believe the market size for COVID, RSV and flu will be over $30 billion by 2027, and we expect to capture $8 billion to $15 billion of this marketplace. While our cost of goods sold percentage will remain elevated in the short term as we transition from a pandemic to an endemic environment, we believe this should normalize to a 20% to 25% range by 2027.

接著 Arpa 先前的發言，我們認為到 2027 年，COVID、RSV 和流感的市場規模將超過 300 億美元，我們預計將從中佔據 80 億至 150 億美元的市場份額。雖然隨著我們從大流行環境過渡到地方性流行環境，我們的銷售成本百分比短期內仍將保持較高水平，但我們相信，到 2027 年，這一比例應該會正常化到 20% 至 25% 的範圍內。

We also laid out a $6 billion to $8 billion cumulative R&D investment required over the next 3 years, which will then normalize to a routine maintenance amount of 10% respiratory vaccines revenue by 2027. Finally, we like the characteristics of the respiratory vaccine franchise, given the highly flexible cost base, low capital intensity, durable future revenue and high potential return, which could lead to $4 billion to $9 billion of free cash flow annually with further room for growth.

我們也預計未來 3 年需要累積投入 60 億至 80 億美元研發資金，到 2027 年，該金額將正常化為呼吸道疫苗收入的 10% 的常規維持額。最後，我們看好呼吸道疫苗特許經營的特點，因為該業務具有高度靈活的成本基礎、較低的資本密集度、持久的未來收入和高潛在回報，每年可產生 40 億至 90 億美元的自由現金流，並且還有進一步的增長空間。

This concludes my remarks, and I will now turn the call back over to Stephane.

我的發言到此結束，現在我將把電話轉回給史蒂芬。

Thank you, Jamey, Arpa and Stephen. Let me share some thoughts before we close into Q&A. Not another promising commercial outlook as several development projects come to fruition. In COVID, we are finalizing discussions with customers. And I believe that we'll see significant additional contracts in the U.S., in Japan and around the world for fall of '23.

謝謝你，Jamey、Arpa 和 Stephen。在我們結束問答之前，讓我先分享一些想法。儘管多個開發項目已經取得成果，但商業前景並不樂觀。在 COVID 方面，我們正在與客戶進行最後的討論。我相信，到23年秋季，我們將在美國、日本和世界各地看到大量額外的合約。

COVID is not going away and governments are getting ready for vaccination campaign in the fall. I'm pleased that we have begun prelaunch market development and as risk manufacturing for RSV, which we expect to launch in '24. And in oncology, the team is making great progress. We expect to deliver key milestones on our development pipeline in the remaining 8 months of 2023. We expect regulatory authorities to give us direction on COVID strain with the June VRBPAC meeting, and we expect to launch an updated COVID-19 vaccine for fall of '23.

COVID 不會消失，各國政府正在為秋季的疫苗接種運動做準備。我很高興我們已經開始進行 RSV 的上市前市場開發和風險製造，我們預計將於 24 年推出。在腫瘤學領域，該團隊正在取得巨大進展。我們預計將在 2023 年剩餘的 8 個月內實現開發流程中的關鍵里程碑。我們預計監管機構將在 6 月的 VRBPAC 會議上為我們提供有關 COVID 病毒株的指導，並且我們預計將在 2023 年秋季推出更新的 COVID-19 疫苗。

We plan to file for approval for RSV vaccine and of Phase 303 flu study should be fully enrolled by this summer, and we expect data in Q4. For INT cancer therapy, we expect to make additional Phase II update, launch of our Phase III study in adjuvant melanoma and expand into additional cancer types. And we'll continue to make progress in our revenues portfolio. We present data for PA on May 18.

我們計劃申請 RSV 疫苗的批准，第 303 期流感研究應該在今年夏天完成招募，我們預計第四季度會有數據。對於 INT 癌症治療，我們期望進行額外的 II 期更新，啟動輔助黑色素瘤的 III 期研究，並擴展到其他癌症類型。我們將繼續在收入組合方面取得進展。我們提供 5 月 18 日 PA 的數據。

This is a very exciting time for us at Moderna, and I would like to thank our teams for all their hard work and their commitment to our mission. Our platform is firing on all cylinders. In Infectious Disease vaccine, look at the data and the portfolio of respiratory, latent and now entering a bacterial vaccine. Very excited by where INT is and is going. And rare disease with PA followed closely by MMA and GSD1a.

對於 Moderna 來說，這是一個非常令人興奮的時刻，我要感謝我們的團隊所做的所有努力以及對我們使命的承諾。我們的平台正在全力運作。在傳染病疫苗中，查看呼吸道、潛伏性和現在進入的細菌疫苗的數據和組合。對 INT 的現狀和未來發展感到非常興奮。罕見疾病有 PA，其次是 MMA 和 GSD1a。

We'll give some key updates this year. On September 13, we have our annual R&D there. We will present new development pipeline data and on December 7, we'll be hosting our second annual ESG day. We believe that the incredible progress we have made across all of our modality, positions our company for long-term financial success. But the mission of our company was to motivate our entire team to come to work every day is to deliver the greatest possible impact to people for mRNA medicine.

我們將在今年提供一些重要更新。 9月13日，我們在那裡舉行年度研發會議。我們將展示新的開發管道數據，並於 12 月 7 日舉辦第二屆年度 ESG 日。我們相信，我們在所有模式上取得的令人難以置信的進步，為我們公司帶來長期的財務成功奠定了基礎。但我們公司的使命是激勵我們整個團隊每天上班，為 mRNA 藥物的人帶來盡可能大的影響。

We believe we have a technology to eliminate or greatly reduced human suffering caused by respiratory viruses, latent viruses, bacteria, cancer, regulating disease and a growing list of other diseases. We work to bring a number of our more promising technologies to market in the next several years and have post to COVID to fulfill on our mission.

我們相信，我們擁有一項技術，可以消除或大幅減少呼吸道病毒、潛伏病毒、細菌、癌症、調節性疾病以及越來越多的其他疾病給人類帶來的痛苦。我們致力於在未來幾年內將一些更有前景的技術推向市場，並在 COVID 之後完成我們的使命。

With this, we'll take questions. Operator?

藉此，我們將回答問題。操作員？

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

（操作員指示）我們的第一個問題來自巴克萊銀行的 Gena Wang。

I have 2 quick questions. The first one is regarding the U.S. commercial opportunity in the second half this year. You are in discussion with both the commercial and government payer, is 110 to 130 still a good benchmark? How is the pricing play out between these 2 groups? When will you start to see clarity on actual contracts and orders? And then my second quick question is regarding your expectation for ASCO update for your PCV program.

我有兩個簡單的問題。第一個是關於今年下半年美國的商業機會。您正在與商業和政府付款人討論，110 到 130 仍然是一個好的基準嗎？這兩組之間的定價情況如何？您什麼時候才能開始清楚了解實際合約和訂單？我的第二個快速問題是關於您對 ASCO 對 PCV 計劃更新的期望。

Great. So I will start with the first 2 questions on commercial and then hand it over to Stephen to discuss ASCO. In terms of pricing across the U.S. market, we do anticipate our list price when we have our updated vaccine to be in the range of 110 to 130. As you're aware, in the commercial market, we will be providing differentiated discounts across different payer types, from government agencies through to commercial players as well.

偉大的。因此，我將從有關商業的前兩個問題開始，然後交給 Stephen 討論 ASCO。就美國市場的定價而言，我們預計更新後的疫苗定價將在 110 至 130 之間。如您所知，在商業市場，我們將為不同類型的付款人（從政府機構到商業參與者）提供差異化的折扣。

In terms of the timing of the orders, we are actively in negotiations with U.S. customers. We are very encouraged on 2 fronts. First and foremost, our customers do appreciate and understand the significant health burden that continued success with COVID. And they do want to partner with us to make sure that as many of their patients can get vaccinated to protect themselves from potential hospitalizations and severe diseases.

關於訂單時間方面，我們正在積極與美國客戶進行協商。我們在兩方面感到非常鼓舞。首先，我們的客戶確實理解並理解持續對抗 COVID 所帶來的巨大健康負擔。他們確實希望與我們合作，以確保盡可能多的患者能夠接種疫苗，以保護自己免受潛在的住院和嚴重疾病的侵害。

The other thing we continue to be very encouraged by in our conversations with different customers if they are appreciating and recognizing the full real-world evidence behind (inaudible) and the effectiveness and profile of our vaccine. So we anticipate over the next 4 to 6 weeks, we will begin to see some more clarity around contracting, which will continue through the end of Q2 and early into Q3.

另一件事是，如果我們在與不同客戶的交談中，能夠欣賞並認可我們疫苗背後的全部現實世界證據（聽不清楚）以及其有效性和概況，我們就會繼續感到非常鼓舞。因此，我們預計在接下來的 4 到 6 週內，我們將開始看到有關合約的更多明朗化，這種趨勢將持續到第二季​​末和第三季初。

(Operator Instructions)

（操作員指示）

Gena had a question on ASCO? Okay. Sorry. Gena (inaudible) presenting at ASCO. So it's Stephen. So as I said, there's 2 presentations, 2 sets of data that will be shared. The first will be focused on the distant metastasis-free survival, DMFS. DMFS, as you know, is another surrogate of overall survival and distant metastasis usually, unfortunately, is visceral, and that's obviously a greater concern.

Gena 對 ASCO 有疑問嗎？好的。對不起。 Gena（聽不清楚）在 ASCO 上發表演說。原來是史蒂芬啊。正如我所說，將會有 2 個簡報和 2 組數據供大家分享。第一個重點是遠處無轉移存活期 (DMFS)。如您所知，DMFS 是整體存活率的另一個替代指標，而遠處轉移通常不幸地發生在內臟，這顯然是一個更大的問題。

The protocol for the Phase II study included in the first analysis, primary analysis, looking both at RFS and distant metastasis-free survival, DMFS was a secondary endpoint, and we'll be presenting for the first time that data at ASCO. The second data that will be shared in poster form will be some data on biomarkers and additional data on the performance of INT across populations. That is data that will get more into the basic science for those who are interested in it, but we'll look into the mechanism of action of the product as well as further stratification of risk that we believe provides even more confidence that the signal we're seeing in terms of potential benefit for INT in the Phase II study is resilient and really bodes well for the future.

II 期研究的方案包括第一次分析，即主要分析，同時關注 RFS 和遠端轉移無生存期，DMFS 是次要終點，我們將首次在 ASCO 上展示該數據。將以海報形式分享的第二份數據是一些有關生物標誌物的數據以及有關 INT 在各個人群中的表現的附加數據。對於那些對此感興趣的人來說，這些數據將更深入地介紹基礎科學，但我們將研究產品的作用機制以及進一步的風險分層，我們相信這可以讓我們更有信心地看到，我們在第二階段研究中看到的 INT 潛在益處的信號是有彈性的，並且確實預示著未來的良好前景。

Our next question comes from Salveen Richter with Goldman Sachs.

我們的下一個問題來自高盛的 Salveen Richter。

With regard to the PA data that we're going to see at ASGCT, could you just frame that for us? I think in the past, you've talked about 25% being clinically meaningful as you look at relative risk reduction in major decompensation events here and what the translatability is from that to MMA and GSD1a and OTC your overall rare disease franchise. And then a second question for COGS, how are you thinking about beyond 2023? And in the context of your assumed market share of the respiratory franchise revenue as you look out to 2027 which you noted, how do you think about profitability in the context of this OpEx spend, including kind of your R&D and SG&A outlook?

關於我們將在 ASGCT 上看到的 PA 數據，您能為我們簡單描述一下嗎？我認為，過去您曾談到 25% 具有臨床意義，因為您在這裡研究的是主要失代償事件的相對風險降低，以及從這一點到 MMA 和 GSD1a 以及 OTC 的整體罕見病特許經營的可轉化性。然後第二個問題是針對 COGS，您對 2023 年以後的情況有何打算？並且，根據您假設的呼吸特許經營收入的市場份額，展望 2027 年，您如何看待在營運支出背景下的盈利能力，包括您的研發和銷售、一般及行政管理前景？

Thank you for the question. So I'll take the rare disease portion of that on PA first. And so as we shared last September, we did a data cutoff from the PA study last September after a couple of dose levels. And we were seeing slightly more than 50% reduction in the rate of metabolic decompensation. These are the severe events that really, we believe, will ultimately be the endpoint that we're measuring for this drug in terms of benefit.

謝謝你的提問。因此我將首先討論 PA 上的罕見疾病部分。正如我們去年 9 月分享的那樣，我們在幾個劑量水平之後對去年 9 月的 PA 研究進行了數據截斷。我們發現代謝失代償率降低了 50% 多一點。我們相信，這些嚴重事件最終將成為我們衡量該藥物療效的終點。

And what we are going to be sharing at ASGCT is the further update to that. And so this will be a March data cutoff. It's about 6 more months and that will also include at least 6 months at the third dose level, 0.5 mpk and some other emerging data at the next dose level. Again, I don't want to get ahead of sharing what that data is. But of course, we will be looking the strength of that benefit, as we go up in dose, we would hope that we would improve from that 50% reduction in the rates of MDEs, approximately 50% reduction in MDEs.

我們將在 ASGCT 上分享有關此事的進一步更新。因此這將是三月的數據截止時間。大約還需要 6 個月的時間，其中還包括第三個劑量水平的至少 6 個月、0.5 mpk 和下一個劑量水平的一些其他新興數據。再次強調，我不想提前透露這些數據是什麼。但當然，我們會關注這種益處的強度，隨著劑量的增加，我們希望 MDE 發生率能夠從 50% 的降低，到大約 50% 的降低。

And we'd also want to obviously see that the drug continues to be very well tolerated with no safety concerns in that patient population. We'll also see much more follow-up time in terms of total time on drug across the entire study which will help to build that case moving forward.

而且我們還希望看到該藥物在該患者群體中仍然具有良好的耐受性並且不存在安全問題。我們也將看到整個研究中藥物使用總時間方面的更多後續時間，這將有助於進一步推進此案例。

Now on the point of relationship to other programs, propionic acidemia, PA is a sister disease to methylmalonic acidemia, MMA. And as we get more and more confident, hopefully, about the dose level in which we're expanding the PA program and the data we're seeing there, we do believe that reads through very directly into the data that we expect to see shortly in MMA. We have started to see some of that data from that Phase II -- Phase I/II study in population.

現在談到與其他項目的關係，丙酸血症 (PA) 是甲基丙二酸血症 (MMA) 的姊妹疾病。並且，隨著我們對擴大 PA 計劃的劑量水平以及我們在那裡看到的數據越來越有信心，我們確實相信，這將非常直接地反映出我們預計很快在 MMA 中看到的數據。我們已經開始看到來自第二階段至第一/第二階段人群研究的一些數據。

I'll remind you that MMA is also chronically dosing in patients and escalating through dose levels. And at the right moment, we will obviously want to provide an update on that data as well in terms of MMA, but we do believe that the PAD to reach really positively through that. And generally, I'd say that's true for our liver metabolic rare disease programs, including OTC and the others that you referenced.

我要提醒你，MMA 也會在病人體內長期服藥，劑量會逐漸增加。在適當的時候，我們顯然也希望提供有關 MMA 方面的最新數據，但我們確實相信 PAD 能夠透過這些數據取得積極進展。總的來說，我認為這對我們的肝臟代謝罕見疾病計畫來說是正確的，包括 OTC 和您提到的其他項目。

And Salveen, maybe I'll take the COGS question. So to reiterate, this year is 35% to 40% of sales. And as you mentioned, we'll go to 20% to 25% by 2027. So I'm not sure it's a perfectly straight line, but let me just give you the factors that will improve that over time.

Salveen，也許我會回答 COGS 問題。所以重申一下，今年的銷售額佔比是 35% 到 40%。正如您所說，到 2027 年，這一比例將達到 20% 到 25%。因此，我不確定這是否是一條完美的直線，但讓我給您一些隨著時間的推移會改善這種情況的因素。

First is volume. So increasing volume over time as we add new products, our overall manufacturing footprint should give us better leverage. I think predictability helps that so this is a highly unknown season this year. It will be the first time we're transitioning to an endemic. So that will become more predictable over time. ASP, I think, will continue to go up as well. What might offset that a little bit is a greater single-dose file or PFS presentation over time, and we've got some of that budgeted for 2023. So overall, we feel confident inverting our inventory levels down and overall decreasing our cost as a percent of sales.

首先是數量。因此，隨著我們添加新產品，產量會隨著時間的推移而增加，我們的整體製造足跡應該會為我們提供更好的槓桿作用。我認為可預測性會有所幫助，所以今年的賽季非常未知。這是我們第一次向地方病轉變。因此，隨著時間的推移，這將變得更加可預測。我認為平均售價也將繼續上漲。隨著時間的推移，單劑量文件或 PFS 演示的增加可能會稍微抵消這一影響，我們已經為 2023 年編制了部分預算。因此，總體而言，我們有信心降低庫存水平，並整體降低成本佔銷售額的百分比。

As it pertains to the 2027 P&L and what does that mean for overall company profitability, we haven't issued any guidance on that. I would say to reiterate for those that heard my prepared remarks, the respiratory vaccine business should generate $4 billion to $9 billion, which we laid out on the page there. And then we'll just have to see, to be honest. We've got an exciting pipeline. We have to understand what's happening with INT. We're quite excited by that, rare diseases, latent diseases as well, and we'll do what's best for all of our stakeholders. So if it makes sense to continue to reinvest some of those profits back into the business, we'll do that. And we're just going to have to sit wait and see where the pipeline looks like at that time.

至於 2027 年損益表以及這對公司整體獲利能力意味著什麼，我們尚未就此發布任何指導。我想向那些聽過我準備好的發言的人重申一下，呼吸道疫苗業務應該能創造 40 億到 90 億美元的收入，我們在那一頁上已經列出了這個數字。然後我們就只能老實看看了。我們有一個令人興奮的管道。我們必須了解 INT 發生了什麼事。我們對此感到非常興奮，包括罕見疾病和潛在疾病，我們將為所有利害關係人提供最好的服務。因此，如果繼續將部分利潤重新投資於業務是有意義的，我們就會這樣做。我們只需要坐下來等待，看看那時管道的情況如何。

Our next question comes from Tyler Van Buren with TD Cowen.

我們的下一個問題來自 TD Cowen 的 Tyler Van Buren。

This is Tara on for Tyler. So I know you mentioned a little bit about timing. But specifically, what we're wondering is, once the COVID strain is selected for the fall and winter season next month, how long approximately do you think it will take to finalize the commercial contracts in the U.S. and abroad? And then separately outside of the U.S., does the recent announcement regarding the ongoing negotiation with Pfizer and Europe actually create an opportunity for you guys to perhaps drive a larger contract in Europe than previously anticipated?

這是 Tara 為 Tyler 表演的。我知道您提到了一點有關時間的問題。但具體來說，我們想知道的是，一旦下個月選定了秋冬季節的 COVID 株，您認為大約需要多長時間才能完成美國和國外的商業合約？那麼，在美國以外，最近宣布的與輝瑞和歐洲正在進行的談判是否真的為你們創造了機會，讓你們在歐洲獲得一份比之前預期更大的合約？

Thank you for the question. Your first question around timing of contracting in the U.S. While we are waiting for the final variant strain to be selected in the middle of June, we have already initiated contracting conversations based on an FDA-selected variant. So as I mentioned previously, we do anticipate seeing some of these contracts being signed over the next several weeks, leading into the third quarter. So it will be sort of an evolving time line based on the customer.

謝謝你的提問。您的第一個問題是關於在美國簽訂合約的時間。雖然我們正在等待 6 月中旬選出最終的變異毒株，但我們已經開始根據 FDA 選定的變異毒株進行合約談判。正如我之前提到的，我們確實預計未來幾週內，也就是第三季度，將會簽署一些這樣的合約。因此，這將是一個基於客戶不斷發展的時間表。

From an EU perspective, we're encouraged by the news that the EU is in renegotiations with Pfizer. For us, the signals that the EU likely does not want to rely on one sole supplier. And we also are encouraged that the EU does recognize the value of the effectiveness and safety of our COVID-19 vaccine. So we continue to work with them to see how we can help protect the 140 million people or so in the EU, who are at high risk of COVID infection. And as we get updates on EU negotiations, we will be sharing those as well.

從歐盟的角度來看，歐盟與輝瑞重新談判的消息令我們感到鼓舞。對我們來說，這表明歐盟可能不想依賴單一供應商。我們也感到鼓舞的是，歐盟確實認識到我們的 COVID-19 疫苗的有效性和安全性的價值。因此，我們將繼續與他們合作，研究如何幫助保護歐盟約 1.4 億人感染新冠病毒風險較高的人。當我們獲得有關歐盟談判的最新消息時，我們也會分享這些資訊。

Next question comes from Michael Yee with Jefferies.

下一個問題來自 Jefferies 的 Michael Yee。

Two areas I wanted to ask on PCV or shall I say, INT cancer therapy. Stephen, you've talked and mentioned there in the slides around time as well as breakthrough designation. And I think you mentioned that you do have a discussion with FDA around your recent data. Can you just talk to the scenarios around a potential accelerated approval, the argument that you have to bring this to patients sooner or do we really have to wait years to run the Phase III? Talk a little bit about how you feel about that this year.

我想問兩個關於 PCV 或 INT 癌症治療的問題。史蒂芬，您在幻燈片中談到了時間以及突破性指定。我認為您提到您確實與 FDA 就您的最新數據進行了討論。您能否談談有關潛在加速審批的情景，即您必須更快地將其帶給患者，還是我們真的必須等待數年才能進行第三階段？談談你今年對此的感受。

And then the second question, I think, is also important with regard to RSV. Obviously, we'd love to see a diversification of revenues. This could be coming next year. How do you see your revenue opportunity in 2024? Is that a payer battle or a couple of competitors out there, where is your advantage? And how do you see yourself with market share and revenues next year?

我認為第二個問題對於 RSV 來說也很重要。顯然，我們希望看到收入的多樣化。這可能會在明年發生。您如何看待 2024 年的收入機會？這是付款人之爭還是幾個競爭對手之間的競爭，你的優勢在哪裡？您認為明年的市佔率和收入會是怎樣？

Thank you, Mike, for the question. I'll take the INT one. So Look, I think it's obviously still early in this discussion about what it will take to bring this medicine forward to patients. And even in the Phase II study, while the data is really exciting, it's probably premature to say that it's sufficient for -- at this point for proceeding directly to accelerated approval. But there are conditions we think over the next year -- or couple of years that could lead to that being an appropriate thing for us and regulators to consider.

謝謝麥克提出的問題。我要選 INT 的。所以，我認為，關於如何將這種藥物帶給患者，現在的討論顯然還處於早期階段。即使在第二階段的研究中，雖然數據確實令人興奮，但現在說它足以直接獲得加速批准可能還為時過早。但我們認為，未來一年或幾年內的情況可能會促使我們和監管機構考慮這項事項。

In the short term, look, the data is still maturing. We still haven't put out the distant metastasis free-survival data. We're going to be doing that at ASCO. We're obviously excited to share that data, and it starts to just build that more complete picture and DMFS because it looks at visceral lesions does start to look towards perhaps some of those more -- the severity of those relapses that are happening.

從短期來看，數據仍在成熟。我們還沒有公佈遠處轉移無生存數據。我們將在 ASCO 上進行此項工作。我們非常高興能夠分享這些數據，它開始建立更完整的圖像，而 DMFS 因為它關注內臟病變，所以確實開始關注其中的一些——正在發生的複發的嚴重程度。

We have additional biomarker data that's coming through in that ASCO presentation as well. And both of those data sets are dealing with the initial analysis, which was 40 events. But I'll remind you, we have an analysis at 51 events, which we think will be when these curves are substantially more mature. Obviously, we haven't crossed that yet. And when we do trigger that 51 of that analysis, we will update the RFS curves. We'll update the DMFS curves.

我們還有來自 ASCO 簡報中的額外生物標記數據。這兩個資料集都處理初步分析，即 40 個事件。但我要提醒你，我們對 51 個事件進行了分析，我們認為這些曲線將會更加成熟。顯然，我們還沒有跨越這個界限。當我們確實觸發該分析中的 51 個時，我們將更新 RFS 曲線。我們將更新 DMFS 曲線。

We'll obviously look at statistics around that. And it will be a point in time for us to understand, let's say, with more than 2.5, maybe 3.5 years of follow-up in total median follow-ups on that study. What do the overall curves look like? What are the hazard ratios? What do the statistics look around that? And then what more have we learned about the MOA from all of the ongoing biomarker work that we've done. So that richer data set I think, is really what we are waiting for to see.

我們顯然會查看相關統計數據。這將是我們要了解的一個時間點，比方說，研究的總中位數追蹤時間超過 2.5 年，也許是 3.5 年。整體曲線是什麼樣的？風險比是多少？統計數據是怎樣的？那麼，從我們正在進行的所有生物標記工作中，我們對 MOA 有了哪些更多的了解呢？所以我認為我們真正期待看到的是更豐富的數據集。

There's a second piece of this, too, though, which is that. Any consideration of an accelerated approval, whether it's for INT or just more generically, Increasingly, it's going to depend upon whether or not you have initiated the confirmatory studies and that's appropriate. Because we've all seen how initiating substantially enrolling the confirmatory studies actually helps make sure that, that answer comes quickly and that accelerated approval can either be converted to a full approval or be adjusted as a result of those confirmatory results. And we're very attuned to that. And so our primary focus right now, while we're waiting for the data to mature from the Phase II is to make sure that we stand up that Phase III study and enroll it as fast as possible.

不過，這還有第二部分，那就是。任何加速批准的考慮，無論是針對 INT 還是更一般的加速批准，都將越來越取決於您是否已啟動確認性研究，並且這是否合適。因為我們都已經看到，啟動大量確認性研究實際上有助於確保快速得到答复，並且加速批准可以轉換為完全批准，或根據這些確認結果進行調整。我們對此非常敏感。因此，在等待第二階段資料成熟的同時，我們現在的主要重點是確保我們盡快進行第三階段研究並招募受試者。

I think the conditions under which we might consider in partnership and discussion with regulators pursuing accelerated approval would really be at some point in the future when that Phase III study is well on the path towards being enrolled obviously not read out yet, but well on the path there being enrolled and where a lot of the other data I had described had matured and continued to show a really compelling pace for the potential benefit here, perhaps even in patient populations they are at higher risk from a stratification perspective as we were sharing in some of the data today. And that those -- that complement the factors would trigger an opportunity to say it's time to bring this medicine to patients in an accelerated way while waiting for the confirmatory read out.

我認為，我們與監管機構合作和討論以尋求加速批准的條件實際上是在未來某個時間點，當 III 期研究順利進入臨床試驗階段時，雖然顯然還沒有公佈結果，但已經進入臨床試驗階段，而且我之前描述的許多其他數據已經成熟，並繼續顯示出真正令人信服的潛在益處，甚至在患者群體中，從分層角度來看，他們面臨的風險更高，正如我們今天分享的風險更高。而這些補充因素將帶來一個機會，在等待確認結果的同時，是時候以加速的方式將這種藥物帶給患者了。

So premature. All of those things still have to happen. So that's why right now our focus is get that Phase III started, get it enrolled and continue to follow this really intriguing story in the randomized Phase II study.

太早了。所有這些事情仍需發生。所以這就是為什麼我們現在的重點是啟動第三階段研究、讓研究對象入組並繼續在隨機第二階段研究中關注這個真正有趣的故事。

And I can take the RSV question. We continue to be very excited about our opportunity to (inaudible) RSV. The profile of our vaccine as we look at the Phase III data for tolerability as well as effectiveness position us at the high end of the competitive landscape. From a safety perspective, to date, we have not seen any neuro adverse events and our serious adverse events were balanced in both arms as well.

我可以回答 RSV 的問題。我們繼續對我們的機會感到非常興奮（聽不清楚）RSV。當我們查看第三階段的耐受性和有效性數據時，我們的疫苗概況使我們處於競爭格局的高端。從安全角度來看，到目前為止，我們還沒有看到任何神經不良事件，而且兩組的嚴重不良事件也保持平衡。

What this means for 2024 is as we look at RSV as a seasonal business, we do anticipate that negotiations will be happening every year in the United States. The repairs will have an opportunity to continue to review the data across multiple players, and we will be working actively to position ourselves in the U.S. commercial market.

對於 2024 年來說，這意味著當我們將 RSV 視為季節性業務時，我們確實預計美國每年都會進行談判。修復將有機會繼續審查多個參與者的數據，我們將積極努力在美國商業市場上佔有一席之地。

Our next question comes from Terence Flynn with Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Terence Flynn。

Great. I was just wondering on INT, if you can comment at all about the design of the Phase III in lung there. And then just what's driving that confidence to move forward at this point? Can you just remind us of any data you have at this point on that front?

偉大的。我只是想知道，您是否可以對肺部第三階段的設計發表評論。那麼此時此刻，究竟是什麼推動著這種信心不斷前進呢？您能否提醒我們一下您目前在這方面掌握的任何數據？

Yes. So it's a couple of things. So first, we did look in the Phase I at non-small cell lung cancer, there were patients in that. Those were not adjuvant patients, but nonetheless, do have some data, biomarker data and other clinical histories, again, not from a controlled study in the Phase I. I think the other confidence is the strength of the mechanism of action that we're seeing and the translation across risk strata in the Phase II study that we've already run, really, we think sets up well as you look at adjuvant indications more broadly, and that's where an adjuvant non-small cell lung cancer, even neoadjuvant non-small cell lung cancer makes a lot of sense from a translatability perspective. And so it's a combination of a little bit of data from that Phase I. The breadth and strength of performance we're seeing in the Phase II for melanoma and obviously, what's been learned with PD-1, PD-1/L1 therapy in adjuvant settings more broadly.

是的。所以這是幾件事。首先，我們確實在第一階段研究了非小細胞肺癌，並且有該類型的患者。那些不是輔助患者，但儘管如此，確實有一些數據、生物標記數據和其他臨床病史，同樣，不是來自 I 期對照研究。我認為另一個信心是我們看到的作用機制的強度，以及我們已經進行的 II 期研究中跨風險層的轉化，實際上，我們認為，當你更廣泛地看待輔助適應症時，這已經很充分了，這就是輔助非小細胞肺癌，甚至新輔助非小細胞肺癌從可轉化性角度來看很有意義的地方。所以它是第一階段的一些數據的組合。我們在黑色素瘤第二階段中看到的表現的廣度和強度，以及顯然在更廣泛的輔助環境中對 PD-1、PD-1/L1 療法所學到的知識。

Our next question comes from Jessica Fye with JPMorgan.

下一個問題來自摩根大通的傑西卡費伊 (Jessica Fye)。

A couple of follow-ups on some of the questions that have been asked already. First, on the U.S. COVID contracts for the fall should we expect updates as those are finalized in real time or more like a combined sort of status report, for example, with 2Q results early on in the third quarter. Second, with the shift to an endemic phase for COVID, do you see any opportunity for improved price for COVID vaccines outside the U.S., for example, in Europe? And lastly, on RSV, how soon do you believe RSV needs to be approved for you to participate in contracting for 2024?

對一些已經提出的問題進行一些後續跟進。首先，關於秋季美國新冠疫情合同，我們是否應該期待更新，因為這些更新是實時完成的，或者更像是一種綜合狀態報告，例如，在第三季度初公佈第二季度業績。其次，隨著 COVID 進入地方性流行階段，您是否認為美國以外地區（例如歐洲）的 COVID 疫苗價格有機會提高？最後，關於 RSV，您認為 RSV 需要多久才能獲得批准才能參與 2024 年的承包？

Thank you. In terms of your first question on providing updates for U.S. commercial contracts, we are not currently committing to real-time updates per contract. But at a minimum, we will be providing updates at our quarterly calls in terms of where we are with U.S. commercial contracts. The second question around ex U.S. pricing, we do not comment on our pricing, but what I can tell you is for the majority of the countries outside the U.S. We are still primarily in a centralized government procurement model. So we have not set endemic or more traditional commercial pricing yet for most of the markets outside of the U.S.

謝謝。關於您關於提供美國商業合約更新的第一個問題，我們目前不承諾對每個合約進行即時更新。但至少，我們將在季度電話會議上提供有關我們與美國商業合約的最新進展。第二個問題是關於美國以外的定價，我們不會對我們的定價發表評論，但我可以告訴你的是，對於美國以外的大多數國家，我們仍然主要採用集中政府採購模式。因此，我們尚未為美國以外的大多數市場設定地方性或更傳統的商業定價。

And the last question, I believe, is on RSV contracting. We are targeting a 2024 launch for RSV, we continue to work through the details of the contracting for the U.S. market in particular. But assuming a 2024 for a launch per our current assumptions, we do believe we will be in time for contracting to launch in 2024 in the U.S. market.

我認為最後一個問題是關於呼吸道合胞病毒的感染。我們的目標是 2024 年推出 RSV，我們將繼續研究針對美國市場的合約細節。但按照我們目前的假設，假設 2024 年推出，我們確實相信我們將及時簽約在 2024 年在美國市場推出。

Our next question comes from Ellie Merle with UBS.

我們的下一個問題來自瑞銀的 Ellie Merle。

Maybe if you could just elaborate a little bit on your confidence in the updated formulation targeting the B strains in influenza. And if you can comment on the dose level if this is studying a higher absolute dose. And just maybe just in terms of this compound, but also just broader in terms of the flu platform as you add additional antigens, just your thoughts on reactogenicity here? And then broadly, with the additional (inaudible) of these compounds? And then second, just in RSV, just a bit of housekeeping. I guess, do you still plan to file this quarter.

也許您可以稍微詳細說明一下您對針對 B 型流感病毒株的更新配方的信心。如果這是研究更高的絕對劑量，您可以評論一下劑量水平嗎？也許只是就這種化合物而言，但隨著您添加額外的抗原，從流感平台的角度來看也更為廣泛，您對這裡的反應原性有何看法？然後廣義上講，這些化合物還有附加的（聽不清楚）嗎？其次，在 RSV 中，只是一些瑣碎的事情。我猜，你還打算在本季提交申請嗎？

So first on the flu question. So we obviously have the immunogenicity data that already came out of the P302 study that shows that we've met noninferiority or would have been considered with noninferiority for the B strains. Even in the Northern Hemisphere, study that's ongoing. And so I think our confidence of being able to clear that bar is high and supported by that data even before we made the improvements in the B strain update for the current Phase III study.

首先談談流感問題。因此，我們顯然已經擁有 P302 研究得出的免疫原性數據，這些數據表明我們已經達到了非劣效性，或者對於 B 株來說已經被認為具有非劣效性。即使在北半球，這項研究仍在繼續。因此，我認為，我們對能夠突破這一標準的信心很高，甚至在我們對目前 III 期研究的 B 株更新進行改進之前，這些數據就支持了我們的信心。

We obviously have a preclinical data. We have a lot of experience with updating our antigens and vaccines now with COVID and others. And so we'll look forward to that data in P303. But I think we believe we will do even better than we just did in the P302 study with noninferiority, and we hope to see that we'll be achieving something perhaps trending towards superiority. But that's not the goal specifically for the study. In terms of reactogenicity, and dose -- I'll just say that we are not changing the dose for this 1010 P303 study is still 50 micrograms, so it's not a change in dose level.

我們顯然有臨床前數據。我們在針對 COVID 和其他疾病更新抗原和疫苗方面擁有豐富的經驗。因此我們期待 P303 中的數據。但我認為，我們相信，在非劣效性方面，我們會做得比 P302 研究更好，我們希望看到我們能夠取得一些可能趨向於優越性的成就。但這並不是該研究的具體目標。就反應原性和劑量而言——我只想說，我們不會改變這項 1010 P303 研究的劑量，仍然是 50 微克，所以這不是劑量水平的變化。

And in general, as we think about reactogenicity across our respiratory pipeline, we have a large number of candidates and vaccines where we've gone to doses substantially higher than 50 micrograms. Even in the flu study, we did that up to 100 micrograms on data we shared before. And we believe that there are populations for whom that works well. And in fact, there are vaccines like our RSV vaccine where 50 micrograms is extremely well tolerated. We're very pleased by that profile to date.

總的來說，當我們考慮整個呼吸道管道的反應原性時，我們有大量的候選藥物和疫苗，其劑量遠高於 50 微克。即使在流感研究中，我們也根據先前分享的數據將濃度提高到了 100 微克。我們相信這種方法對某些人群來說是很有效的。事實上，像我們的呼吸道合胞病毒疫苗這樣的疫苗，50 微克的耐受性非常好。到目前為止，我們對該概況感到非常滿意。

And so we actually think it's going to be a vaccine by vaccine case. You can't look at the dose and decide. And as we start going into combinations, we will be optimizing the reactogenicity, the tolerability profile of that vaccine against the benefits in terms of high efficacy that we hope to deliver and often measured by immune responses in those combination studies. So we currently don't believe that there's a limit on that. But in the specific P303 study, we're continuing down a 50 microgram dose level for 1010.

因此，我們實際上認為這將是逐一接種疫苗的結果。您不能透過查看劑量來決定。當我們開始進行組合治療時，我們將優化疫苗的反應原性和耐受性，以實現我們希望實現的高效性，這通常透過組合研究中的免疫反應來衡量。所以我們目前認為這沒有限制。但在具體的 P303 研究中，我們繼續將 1010 的劑量水平降至 50 微克。

Now on RSV, yes, we are working closely with regulators on filing globally. And that includes all of the markets in which we hope to commercialize that product and launch it next year. And of course, we'll keep you appraised as we move into those regulatory -- that regulatory process in our normal quarterly updates.

現在就 RSV 而言，是的，我們正在與監管機構密切合作，在全球範圍內進行備案。其中包括我們希望將該產品商業化並於明年推出的所有市場。當然，隨著我們進入監管階段，我們會在正常的季度更新中隨時向您通報監管流程的進展。

Our next question comes from Luca Issi with RBC.

我們的下一個問題來自 RBC 的 Luca Issi。

Maybe on INT, I think you've been highlighting the opportunity adjuvant and neoadjuvant settings. However, I wonder if you could comment on what's the plan in the metastatic settings, is there a place for INT to metastatic settings? And maybe related to it, are you planning to update the metastatic, and the next cancer data set that we have seen at 50 2021? Any color there much appreciated.

也許在 INT 上，我認為您一直在強調機會輔助和新輔助設定。但是，我想知道您是否可以評論一下轉移設定中的計劃是什麼，INT 是否有轉移到轉移設定的位置？也許與此相關的是，您是否計劃更新我們在 2021 年 50 歲時看到的轉移性和下一個癌症數據集？任何顏色都值得讚賞。

Great. Thank you for this question. So I think we do think that INT can go both earlier and later in terms of its use. And it's a challenging question about which one do we prioritize in the short term. I think there's a huge opportunity we perceive, we believe, in adjuvant. That is where you hear all of our current activities. That's our focus. That's where we're trying to move into pivotal studies, very, very quickly Phase III studies. But if you look to adjuvant, we do have adjuvant experience. You pointed to the head and neck data. We also have from our Phase I somatic melanoma, there's actually some adjuvant -- sorry, the metastatic melanoma. Metastatic non-small cell lung cancer.

偉大的。感謝您的提問。因此我認為我們確實認為 INT 的使用可以更早或更晚。而短期內我們該優先考慮哪一個，這是一個頗具挑戰性的問題。我認為，我們認為，我們相信，輔助治療領域存在著巨大的機會。在這裡您可以聽到我們目前的所有活動。這就是我們的重點。我們正試圖進入關鍵研究階段，非常快速地進入第三階段研究。但如果您考慮佐劑，我們確實有佐劑經驗。您指出了頭部和頸部的數據。我們的第一階段體細胞黑色素瘤也有一些輔助治療──抱歉，是轉移性黑色素瘤。轉移性非小細胞肺癌。

And I think those are situations where we think the burden of the tumor, the size of that tumor is a little bit of a barrier to the potential active activity of any immune therapy. In fact, generally, immune therapies have struggled in later-stage disease and where the real power of the technology, its safety tolerability profile, potential benefit probably is upstream. So while we are following closely the metastatic space, and we did see some intriguing signs in the metastatic head and neck study that you referenced.

我認為在這些情況下，我們認為腫瘤的負擔、腫瘤的大小對任何免疫療法的潛在活性都是一種障礙。事實上，一般來說，免疫療法在晚期疾病中舉步維艱，而該技術的​​真正力量、其安全耐受性概況和潛在益處可能仍處於上游。因此，當我們密切關注轉移性領域時，我們確實在您提到的轉移性頭頸部研究中看到了一些有趣的跡象。

We are right now waiting for a little more data to decide whether or not we want to go into those metastatic settings in the short term with our partner, Merck, of course. The other area that I referenced is the earlier stage. And so Stage IIIa, Stage II disease. Disease where immune therapies are not traditionally used right now, but we're a well-tolerated approach like INT that we believe does provide a boost of specific T cell responses against the cancer might have a unique benefit. And again, that's a place that we're eager to explore the INT approach with our partner Merck in the very near term.

我們目前正在等待更多的數據來決定是否要在短期內與我們的伴侶默克一起進入這些轉移性環境。我提到的另一個領域是早期階段。因此，IIIa 期、II 期疾病。對於目前傳統上不使用免疫療法的疾病，但我們採用一種耐受性良好的方法，如 INT，我們相信它確實可以增強針對癌症的特定 T 細胞反應，這可能會帶來獨特的益處。再次強調，我們渴望在近期與我們的合作夥伴默克公司一起探索 INT 方法。

We don't have at the present as substantial an effort going into those 2 areas, but we could pivot very quickly. So for now, what we're focusing on is the pivotal studies in adjuvant, we're watching very closely the evolution of our data in metastatic, and we're trying to think about how we could move whether biomarker enabled or otherwise into earlier-stage diseases, I'm sure we will find ways to explore all of those areas if there's a potential for benefit for INT and then it's just now a matter of working down the opportunities as fast as we can.

目前我們還沒有在這兩個領域投入大量精力，但我們可以快速轉變方向。因此，目前，我們關注的是輔助治療的關鍵研究，我們正在密切關注轉移性治療數據的發展，我們正在嘗試思考如何將生物標記應用於早期疾病，我相信如果 INT 有可能帶來益處，我們就會找到探索所有這些領域的方法，現在的問題是盡快抓住機會。

Fantastic. And maybe if I can follow-up. When is the earliest that you can have the COVID plus flu combo potential in the market?

極好的。也許我可以跟進。最早什麼時候可以在市場上推出 COVID 和流感組合藥物？

I'll comment for (inaudible) very quickly, but the combination vaccine -- so the first point is we want to need to get the flu approved. I think in the Vaccines Day, we talked about our expectations, our hope are to have the COVID-flu combo approved and launched in 2025.

我很快就會對（聽不清楚）發表評論，但是聯合疫苗——所以第一點是我們需要獲得流感疫苗的批准。我想在疫苗日，我們談到了我們的期望，我們希望新冠-流感疫苗組合能夠在 2025 年獲得批准並推出。

Our next question comes from Geoffrey Meacham with BoA.

我們的下一個問題來自美國銀行的 Geoffrey Meacham。

This is Alex Hammond on for Geoff Meacham. So given the breadth of your clinical pipeline and the potential opportunities for new vaccines, how does Moderna prioritize assets or indications to go after? And once (inaudible) has, let's say, proof of concept for its Lyme disease, what is your clinical strategy in terms of targeting additional bacterial indications? And then just finally, how are you thinking about capital deployment for the INT program?

這是 Geoff Meacham 的 Alex Hammond。那麼，考慮到您的臨床產品線的廣度和新疫苗的潛在機會，Moderna 如何優先考慮資產或適應症？一旦（聽不清楚）有了萊姆病的概念證明，那麼針對其他細菌適應症的臨床策略是什麼？最後，您如何考慮 INT 計畫的資本部署？

I'll take the first question. I'll take all 3, I think, but I invite my colleagues to come in too. So first on how we think about opportunities. It's a great challenge we have. We're obviously seeing a very high success rate as we transition into patient populations or pivotal studies across our pipeline. And the short version of it is we look for places where we think our technology through its modalities is well validated. And so we have a high, hopefully differentiated probably success in that next indication and where there is a large unmet need in that indication.

我來回答第一個問題。我想我會全部參加這 3 場，但我也會邀請我的同事參加。首先談談我們如何看待機會。這是我們面臨的巨大挑戰。當我們轉向患者群體或整個管道的關鍵研究時，我們顯然看到了非常高的成功率。簡而言之，我們尋找那些我們認為我們的技術透過其模式得到充分驗證的地方。因此，我們希望在下一個適應症中取得較高的、有差異化的成功，並且在該適應症中存在大量未滿足的需求。

If there's a large unmet need medically, there is usually a large unmet need financially in terms of health care systems, and that's ultimately the kind of value we want to deliver into it. So that's how we approach it. That can be infectious diseases. That's how we think about expanding our respiratory franchise. That's how we're thinking about expanding our latent franchises. We established there. And what you're going to be seeing us do in rare diseases, as we are already doing, is that same sort of expansion as we start to see proof of concept in the rare metabolic disease space.

如果在醫療方面存在大量未滿足的需求，那麼在醫療保健系統方面通常也會存在大量未滿足的財務需求，而這正是我們最終想要實現的價值。這就是我們的處理方式。那可能是傳染病。這就是我們對擴大呼吸特許經營權的想法。這就是我們擴大潛在特許經營權的想法。我們在那裡建立。您將會看到我們在罕見疾病領域所做的，正如我們已經在做的一樣，也是當我們開始在罕見代謝疾病領域看到概念驗證時進行的同樣的擴展。

And then, of course, you asked a question about INT and maybe I'll just jump to the third part of your question, which is how do we think about capital allocation in terms of in INT. There are very few things that have a larger burden of disease, social cost of -- financial costs of obviously a lot morbidity and mortality than cancer. And we do believe that INT has the potential to be a transformational treatment in that space. And so we got to figure out how to do is how do we responsibly, but aggressively grow that investment across a range of different places where we believe that INT will work.

然後，當然，您問了一個關於 INT 的問題，也許我會直接跳到您問題的第三部分，即我們如何考慮 INT 的資本配置。很少有疾病比癌症造成更大的疾病負擔、社會成本——顯然發病率和死亡率更高。我們確實相信 INT 有潛力成為該領域的變革性治療方法。因此，我們必須弄清楚如何負責任地、積極地在我們認為 INT 能夠發揮作用的一系列不同地方增加投資。

Now we have one significant advantage in that exercise, which is we have a partner in Merck, who has a high degree of conviction around this as well as we talked about, and we are co-investing with them. And so from a capital allocation perspective, we start together looking at what are the indications where there is an opportunity, unmet need in oncology with INT.

現在我們在這項活動中有一個顯著的優勢，那就是我們在默克公司有一個合作夥伴，他們對此有很高的信心，正如我們談到的，我們正在與他們共同投資。因此，從資本配置的角度來看，我們開始共同研究哪些跡象顯示存在 INT 腫瘤學的機會和未滿足的需求。

As I said before, big focus right now is in adjuvant, but of course, we'll be looking at metastatic and earlier stage disease as well. Last question, I think I'll address is the middle one, which is how do we think about lyme POC and what does it unlock in terms of bacteria. I think we're very keen to address lyme because of the unmet need associated with lyme disease, particularly in the northern -- in Europe and the United States.

正如我之前所說，目前的重點是輔助治療，但當然，我們也會關注轉移性和早期疾病。最後一個問題，我想我要回答的是中間的一個問題，那就是我們如何看待萊姆病 POC，以及它在細菌方面能揭示什麼。我認為我們非常熱衷於解決萊姆病問題，因為萊姆病相關的需求尚未得到滿足，特別是在北部——歐洲和美國。

But it is a very interesting one for us to demonstrate a bacterial -- antibacterial vaccination. We already have a substantial discovery pipeline looking at other bacteria that if we can demonstrate proof-of-concept in lyme that we will bring forward very quickly. I won't provide updates on those specific targets as that is still preclinical research. But you rest assured, our approach in bacteria will look like our approach in respiratory or latent or INT or rare diseases, which is as we see proof of concept. We will double down quickly with other programs that we think have high probability of success.

但對我們來說，展示細菌——抗菌疫苗是非常有趣的。我們已經有大量的研究管道在研究其他細菌，如果我們能夠在萊姆病中證明概念驗證，我們很快就會推進。我不會提供這些具體目標的最新消息，因為這仍處於臨床前研究階段。但請您放心，我們針對細菌的方法與我們針對呼吸道疾病、潛伏性疾病、INT 或罕見疾病的方法類似，這就是我們所看到的概念證明。我們將迅速加倍投入我們認為成功機率較高的其他項目。

Our next question comes from Simon Baker with Redburn. Simon, your line is open. You can ask your question.

我們的下一個問題來自 Redburn 的 Simon Baker。西蒙，你的線路已開通。你可以提出你的問題。

Did you want me to remove Simon from the queue?

你想讓我把西蒙從隊伍中移除嗎？

Yes, you can go to the next question. It will be our last question. Thank you.

是的，您可以進入下一個問題。這是我們的最後一個問題。謝謝。

Our last question comes from Hartaj Singh with Oppenheimer.

我們的最後一個問題來自奧本海默的 Hartaj Singh。

This is Eka on for Hartaj today. So in the slides, you have provided the estimated 2027 respiratory product sales range with the high end being almost double or below. I'm curious if you can talk about to what extent does the stand-alone versus combination share of respiratory vaccines affect this revenue range, and we're just trying to understand the sense -- the degree of like market cannibalization by the combo vaccines? And then secondly, a question on the pediatric RSV program. So the burden of disease for children and caused by RSV is immensely high. Can you talk about your progress in the context of competition in the pediatric RSV program and potential time lines for development.

今天是 Eka 為 Hartaj 主持的節目。因此，在幻燈片中，您提供了預計的 2027 年呼吸產品銷售範圍，其中高端幾乎是兩倍或更低。我很好奇，您是否可以談談呼吸道疫苗的獨立份額與組合份額對這一收入範圍的影響程度，我們只是想了解組合疫苗對市場蠶食的程度？其次，我有一個關於兒科 RSV 計劃的問題。因此，呼吸道合胞病毒造成兒童的疾病負擔非常高。您能否談談您在兒科 RSV 專案競爭背景下的進展以及潛在的發展時間表。

Sure. Thank you. I'll start with the first question around the respiratory opportunity. We are hearing significant enthusiasm from both consumers as well as our customer base combination vaccines. We believe that it will enhance compliance and adherence to address the broad respiratory burden of disease by putting these 2, potentially 3 vaccines into 1. So as we think about the commercial opportunity, we do think combinations will be the majority of the opportunity as we look forward in the 2027 and with that, we do anticipate cannibalization of the monotherapy.

當然。謝謝。我將從有關呼吸機會的第一個問題開始。我們聽到了消費者和客戶群對組合疫苗的極大熱情。我們相信，將這兩種甚至可能是三種疫苗合併在一起，可以提高依從性和堅持性，從而解決廣泛的呼吸系統疾病負擔。因此，當我們考慮商業機會時，我們確實認為，組合療法將是 2027 年的主要機會，我們確實預計單一療法將會被蠶食。

Just add efficacy, too. So as we continue to improve our products over time, particularly in flu and COVID, I think the better the strain matches better the efficacy, I think, will also advantage us in the future.

也只是增加功效。因此，隨著我們不斷改進產品，特別是在流感和 COVID 方面，我認為病毒株匹配得越好，療效就越好，我認為這也會對我們未來有利。

And pediatric RSV question. So we've actually been working in pediatric RSV as long as we've been in RSV. And so we have ongoing clinical trials including monotherapy and combination respiratory vaccines across a couple of different diseases that impact that population. We completely agree. It is a huge unmet need and area. In terms of guiding forward what timing will look like, we're conducting clinical research.

以及兒科呼吸道合胞病毒 (RSV) 問題。因此，我們實際上一直在研究兒科 RSV，因為我們一直在研究 RSV。因此，我們正在進行臨床試驗，包括針對影響該族群的幾種不同疾病的單一療法和聯合呼吸道疫苗。我們完全同意。這是一個巨大的未滿足的需求和領域。在指導時間安排方面，我們正在進行臨床研究。

We'll provide the updates on the data as we see it. We've already actually shared some of the early data from our pediatric programs. There will be both seropositive. So kids who have previously been RSV, there is some benefit there. People -- those children do get reinfected. And that will look more like a boosting set of studies. And then there will be seronegative children. Those are the places where there might be the highest unmet need, those who have not yet had their first instance of RSV, so very young children onto the age of 1. What you'll probably see us do over time is bifurcate those development programs because it end up being very different take -- target populations. And more likely than not the seropositive will move faster and the seronegative will move slower as is normally the case with pediatric development.

我們將及時提供最新數據。我們實際上已經分享了一些來自兒科計畫的早期數據。兩种血清反應都會呈陽性。因此，對於先前感染過呼吸道合胞病毒的兒童來說，這會有一些好處。人們──那些孩子確實會再次被感染。這看起來更像是一組促進性的研究。然後就會出現血清陰性的兒童。這些地方可能存在著最未滿足的需求，那些尚未首次感染呼吸道合胞病毒的人，也就是年齡從很小到 1 歲的兒童。隨著時間的推移，您可能會看到我們將這些發展計劃一分為二，因為最終的目標群體會截然不同。而且更有可能的是，血清陽性會移動得更快，而血清陰性會移動得更慢，就像兒科發育的正常情況一樣。

Ladies and gentlemen, this does conclude our Q&A session. I'd like to turn the call back over to Stephane Bancel for any closing remarks.

女士們、先生們，我們的問答環節到此結束。我想將電話轉回給 Stephane Bancel，請他做最後發言。

Well, thank you, everybody, for joining us today and for your questions. The next month is going to be exciting. PA data, May 18 and new INT data at ASCO in Oregon. Have a great day. Bye.

好吧，謝謝大家今天的參與和提問。下個月將會令人興奮。 5 月 18 日的 PA 資料和俄勒岡州 ASCO 的新 INT 資料。祝你有美好的一天。再見。

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

女士們、先生們，今天的演講到此結束。現在您可以斷開連接，享受美好的一天。