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.

美好的一天，謝謝你的支持。歡迎來到 Moderna 2023 年第一季度電話會議。 （操作員說明）請注意今天的會議正在錄製中。

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

我現在想將會議交給今天的發言人 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。大家早上好，感謝您參加今天的電話會議，討論 Moderna 2023 年第一季度的財務業績和業務更新。您可以訪問我們網站的投資者部分，訪問今天上午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首席執行官 Stephane Bancel；我們的總裁 Stephen Hoge；我們的首席商務官 Arpa Garay；和我們的首席財務官 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案》的安全港條款作出的前瞻性陳述。

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.

請參閱隨附演示文稿的幻燈片 2 和我們向美國證券交易委員會提交的文件，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.

有了這個，我會把電話轉給斯蒂芬。

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。大家早上好或下午好。今天，我將從業務回顧開始，然後在 Arpa 提供我們的商業進展和計劃的最新信息之前，Stephen 將回顧我們的臨床項目。 Jamey 將介紹我們的財務結果，我會回來結束。

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，我們的收入為 19 億美元，GAAP 淨收入為 7900 萬美元，GAAP 攤薄後每股收益為 0.19 美元。本季度末現金和現金投資為 164 億美元。我們在第一季度繼續執行我們的資本配置戰略，優先投資我們的業務。第一季度，我們在研發上投資了 11 億美元，繼續投資於後期臨床項目，並在整個管道中取得進展。

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.

本季度的 SG&A 成本約為 4 億美元，其中包括對數字和 AI 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）團隊非常活躍。這包括收購日本的 OriCiro，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 的 mRNA 技術的範圍。

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 操作系統。本季度通過購買 360 萬股股票向股東返還了 5.26 億美元。讓我在第一季度轉向商業。

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 2023 年已經簽署的預購協議將交付 50 億美元的 COVID 疫苗。憑藉第一季度 18 億美元的 COVID 銷售額，我們正朝著實現 50 億美元的 APS 邁進。商業團隊正在積極談判與主要市場的客戶簽訂新合同，以敲定額外的訂單，將增加 50 億美元。美國團隊正在與連鎖藥店、醫院網絡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.

提醒一下，已簽署的 50 億美元 APA 不包括任何 2023 年秋季的美國合同。因此，這些新的美國商業合同對企業很重要，因為它們是額外的。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/地區取得進展。我們最近在澳大利亞簽署了一份 2023 年的新合同。我們的商業組織也在為 2024 年推出 RSV 做準備。我們的下一個呼吸商業產品。他們正在就 RSV 的健康負擔對醫學界進行教育。我們的醫療團隊正在參加主要的傳染病醫學大會並分享新數據，這些數據顯示了我們 RSV 疫苗的強大概況。為了準備我們的 RSV 發布，我們的製造團隊已經開始生產原料藥，即用於 RSV 疫苗的 mRNA 分子。疫苗將作為預裝注射器提供。我們相信這將有助於推動藥劑師和醫生對我們的一些 RSV 產品的採用。

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.

在腫瘤學方面，對於現在稱為個體化新抗原療法或 INT 的 mRNA-4157，我們正在擴大製造規模以支持臨床開發和商業市場。我們的商業團隊也在努力確定腫瘤類型的優先順序，以選擇除黑色素瘤和肺癌之外的其他 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 疫苗的概況可能是同類最佳的。我們分享了宣布啟動 303 期的 2 個項目的頂級數據，這是我們打算用於加速批准的 III 期研究以及我們下一代流感項目的戰略。我們還宣布了下一代 COVID 疫苗 mRNA-1283 的 III 期開始，該疫苗應該是冰箱穩定的。

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，我們還宣布了一項新的 H5 流感大流行準備計劃。在潛伏疫苗方面，我們的 CMV III 期試驗繼續取得進展，並且參與率超過 50%。我也很高興地宣布我們的早期項目 EBV 和 HIV 取得了進展。如您所知，EBV 有 2 個程序。用 mRNA-1189 預防單核細胞增多症的 EBV I 期試驗已完全納入成人和青少年。我們用於治療 EBV 感染長期並發症的 EBV 試驗現已開始招募。對於艾滋病毒，我們將在疫苗日對我們的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.

我們還引入了新程序。我們正在研究針對諾如病毒和萊姆病的疫苗。萊姆病是我們使用 mRNA 平台（聽不清）疫苗瞄準的第一種細菌病原體。在治療學方面，我們參加了 AACR 會議，會上我們展示了與默克公司合作的 INT 項目的詳細 II 期數據。稍後在電話中，斯蒂芬將帶您瀏覽那裡提供的數據。

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.

這條管道也正在取得進展。我們很高興地宣布 PA 計劃的新里程碑。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晚些時候在 5 月份的美國基因與細胞治療學會上公佈。

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，這反映了本季度包含了新項目（聽不清），並刪除了不再繼續開發的項目。可以在本演示文稿的附錄中或在我們的網站上清楚地看到這些管道的全部內容。我們現在在美洲、歐洲和亞太地區擁有 4,000 多名團隊成員和 17 家商業子公司。

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，我們還宣布將開設西雅圖辦事處作為技術中心，我們正在招聘數據科學家和工程師，他們將幫助我們實現業務數字化並擴展我們的 AI 能力。我也很高興地宣布，Moderna 在 3 月份被 Great Place To Work Institute 正式認可為 Great Place To Work。我們在另一個季度的 164 億美元現金使我們能夠擴展我們的研究、開發、製造、商業和 G&A。

With that introduction, let me now turn to Stephen.

有了這個介紹，現在讓我轉向斯蒂芬。

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，斯蒂芬。大家早上好或下午好。今天，我將回顧第一季度 Moderna 研發的臨床進展，並重點介紹過去幾個月的精選數據。我們呼吸系統產品組合的核心由針對 COVID-19、流感和 RSV 的疫苗組成，這些疫苗已經上市或處於 III 期。我們正在推進第二代疫苗，包括我們的第二代冰箱穩定 COVID-19 候選疫苗 mRNA-1283，它正在迅速進入其 III 期研究，以及 2 種處於 II 期的下一代流感疫苗。我們相信聯合疫苗將是我們呼吸道專營權的未來。我們很高興現在有 5 種不同的候選聯合疫苗處於早期臨床試驗階段，其中 2 種是專門為兒科人群設計的。

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.

我們有 11 個臨床試驗項目，其中 4 個處於 III 期，涵蓋 5 種不同的呼吸道病毒，我們相信這代表了最廣泛和最先進的呼吸道病毒候選疫苗組合。現在專門轉向 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 最近提供了幾個方面的更新。我們針對原始菌株和 BA.4/5 菌株的 Omicron 靶向二價 COVID-19 疫苗現在是我們在美國唯一獲得授權的製劑，為兒童和成人提供簡化和精簡的方案。個人、65 歲和具有某些免疫功能低下的人現在也有資格根據需要或醫生推薦接受額外劑量。

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，2023 年秋季助推器更新成分的菌株選擇現在預計將在 6 月 15 日的 VRBPAC 會議上進行。轉向 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.

在我們的大型 III 期研究中，我們對我們的疫苗在老年人群中對 RSV 下呼吸道疾病具有高效且一致的功效感到滿意。在最近的 2 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組中的功效始終很高，包括對最年長的成年人和患有使他們面臨更高風險的既往合併症的參與者。

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 還顯示出良好的耐受性，AE 大多為 1 級或 2 級，輕度至中度。正如我們在疫苗日分享的那樣，今天，我們在試驗中沒有看到任何格林-巴利綜合徵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積累足夠的案例，無法在中期分析中宣布早期成功，DSMB 建議我們繼續研究。在這個流感季節結束之前，該試驗仍在累積病例，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.

來自 P302 研究的初步免疫原性數據表明，與獲得許可的流感疫苗相比，HAI 中和效價與 A 株的優勢和 B 株的非劣免疫原性一致。現在，我很高興地宣布，我們已經啟動了我們的 III 期 P303 流感研究，該研究採用了更新的 mRNA-1010 配方。 P303 正在測試旨在提高針對 B 抗原的 HAI 中和滴度的更新。這是一項免疫原性研究，預計今年春天將招募大約 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報，以及如果監管機構批准，2024 年推出的潛力。

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.

現在轉向我們的潛伏疫苗。我們針對女性和育齡期的 CMV 疫苗 III 期研究正在進行中，並且已經招募了超過 50% 的參與者。我們還正在進行一項針對該疫苗的 I/II 期青少年劑量範圍研究，該研究將擴大潛在的合格人群。正如 Stephane 之前提到的，我們繼續在早期臨床試驗中針對所有潛伏疫苗取得重大進展，包括針對 EBV、HIV 和 VZV 的候選疫苗。正如 Stephane 提到的，我們的 EBV 疫苗包括 2 個候選疫苗，我們的 EBV 項目包括 2 個候選疫苗 mRNA-1189 和 mRNA-1195，並且正在進行臨床試驗，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。

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.

現在在疫苗日，我們很高興分享我們的 HIV 疫苗 mRNA-1644 的中期結果，該疫苗繼續取得進展。我們的治療產品管線針對免疫腫瘤學、罕見疾病、心血管疾病和自身免疫性疾病中未滿足的需求。這些治療領域的所有試驗都在進行中。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.

在幻燈片 16 上，我們在 AACR 上分享的數據來自我們的輔助黑色素瘤 II 期研究，結合我們的個體化新抗原療法加 KEYTRUDA 與單獨使用 KEYTRUDA 的比較。此處為無復發生存解決方案的 Kaplan-Meier 曲線。總體而言，與單獨使用 KEYTRUDA 相比，聯合使用 INT 和 KEYTRUDA 的複發率或死亡率降低了 44%。我們對 18 個月隨訪時兩條曲線的持續分離感到鼓舞。請注意，超過這張幻燈片右側的 140 週截止值的參與者很少，總共不到 10 名參與者。因此，隨著數據的不斷成熟，隨著後續時間的延長，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.

現在在幻燈片 17 上，我想簡要強調一些在 AACR 上共享的附加數據。亞組分析證實了 2 個已知預測對 KEYTRUDA 反應的重要標誌物的治療效果強度。同樣，在這張幻燈片上，我們正在研究無復發生存期。

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，結果按紅色的高腫瘤突變負荷和藍色的低腫瘤突變負荷分層。在每種情況下，實線表示 INT 組合，虛線表示 KEYTRUDA 單一療法對照。如果您首先查看和比較 KEYTRUDA 的控制臂，您會注意到 TMB 高參與者（紅色虛線）比藍色虛線中 TMB 低參與者的無復發生存率更高。這是意料之中的，因為我們對 KEYTRUDA 的了解，並表明控件的性能符合我們的預期。

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 組合臂，實線並將它們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率。這突出了 INT 響應的穩健性。同樣令人興奮的是，藍色 TMB 低人群的反應率有所提高，這在歷史上對 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，您會看到按 PD-L1 狀態分層的結果。現在與 TMB 分析一樣，已知 PD-L1 可以預測免疫療法的反應率。正如您通過 KEYTRUDA 單藥治療對照組的虛線所見，PD-L1 陽性腫瘤的無復發生存曲線看起來更好，這些是紅色虛線，對於不幸的 PD-L1 陰性腫瘤患者更糟，藍色虛線。這並不奇怪，因為 KEYTRUDA 單一療法通過阻斷 PD-1、PD-L1 通路起作用。

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 曲線上的實線顯示了 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，聯合治療的無復發生存率都有所提高。再次令人鼓舞的是，PD-L1 陰性患者的反應率顯著提高。實際上，該亞組分析中的風險比為 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.

現在回過頭來看，這些數據強調，在我們的 II 期研究的初步分析中觀察到的無復發生存期改善看起來具有廣泛的跨亞組基礎，表明即使在進展風險較高的患者中也有潛在的重要益處，與單獨使用 KEYTRUDA 單一療法相比，無論是由於 PD-L1 狀態還是腫瘤突變負荷。

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。我們將分享來自 ASCO II 期研究的額外數據，包括無遠處轉移生存期，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削減。我們還將分享重要的額外生物標誌物數據。此外，該協議要求對 51 個事件進行後續分析，屆時我們還將更新 Kaplan-Meier 曲線以實現無復發生存，並在整個人群中進行更長的隨訪時間，我們熱切等待這些更新。

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 在美國獲得了突破性療法，在歐洲獲得了 PRIME 稱號，這將促進與監管機構的頻繁對話，因為我們致力於為患者快速推進這種治療。正如 Stephane 之前提到的，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。我們正在與我們的合作夥伴默克公司密切合作，探索 KEYTRUDA 批准的適應症和該標籤之外的更多機會。最後，快速更新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臂。就在昨天，我很高興地宣布，通過今年早些時候的時間點進行臨床更新，包括更新安全性和來自更高劑量組的主要代謝失代償率以及包括來自現在將在 5 月 18 日的美國基因和細胞治療協會會議上介紹較低劑量的隊列。該演示文稿的摘要現在可用，可以在本幻燈片的鏈接中找到。我們期待在未來幾個月內分享更多關於這種藥物和我們其他罕見病項目的進展。

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

有了這個，我會把電話轉給 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，斯蒂芬，祝大家有美好的一天。我將首先回顧本季度的銷售情況。在幻燈片 22 上，我們總結了第一季度的銷售額構成。正如您在圖表中看到的，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。 2023 年第一季度，先前宣布的 APA 的銷售額約為 18 億美元，佔 2023 年上半年預期銷售額 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 COVID 疫苗的銷售預計將於 2023 年下半年開始，並提供更新的毒株匹配疫苗。現在我們轉向幻燈片 23，看看 2023 年的 COVID 交付，今天，我們重申根據當前的預先採購協議至少交付約 50 億美元的 COVID 疫苗。我們繼續期待來自主要市場的額外訂單。在之前宣布的 APA 的 2023 年交付的 50 億美元中，正如我之前提到的，預計將在 2023 年上半年交付 20 億美元。我們已經在第一季度交付了這 20 億美元中的 18 億美元，並實質性地履行了日本和歐盟。我們預計將在今年下半年交付先前宣布的 APA 中剩餘的約 30 億美元。此外，我們預計在美國、日本、歐盟、亞洲和拉丁美洲會有新的銷售。我很高興地宣布，商業團隊已經與澳大利亞政府簽署了 2023 年的合同。

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，我將在稍後詳細說明。在我們與美國商業客戶的討論中，很明顯，我們的客戶意識到 COVID 仍然是一個巨大的健康負擔。整個 2022 年，COVID 仍然是住院的主要原因。截至 2022 年 9 月可用的數據將 COVID 列為美國第三大死亡成本，僅次於心髒病和癌症，如左圖所示。幻燈片右側的圖表顯示了美國因 COVID、流感和 RSV 住院的最新數據。正如您將看到的，由於當前季節每個 COVID 的住院人數超過 600,000，因此 COVID 的住院率幾乎是流感的三倍以及 RSV 的三倍多。仍然明顯需要防止嚴重的 COVID 感染，我們的客戶認識到這種需求。

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，我們預計美國市場容量約為 1 億劑。正如我們在今年早些時候強調的那樣，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，正在執行我們快速發展這個商業市場的行動計劃。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房、綜合交付網絡、政府衛生提供者（包括 VA、CDC 和國防部）簽訂採購合同，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我們的 Moderna Direct 電子商務網站已全面投入運營。我們的全球供應鏈已到位，可以滿足所有美國客戶的需求，包括上市時的預裝注射器和單劑量藥瓶。我很高興與大家分享秋季疫苗接種活動更新後的 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，我們正在通過向醫療保健提供者量身定制的數字消息傳遞來採用全渠道方法。這種多方面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，我們將傳播定制內容，以推動免疫醫師、機構決策者和影響者的需求。

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.

我們還與不同商業領域的客戶群合作，協助他們開展秋季免疫計劃。我們相信有機會繼續為員工和患者提供教育。我們相信有機會協調和簡化將要跳過流感疫苗的患者的疫苗接種過程。

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.

消費者促銷將主要集中在今年秋季，通過重大的 DTC 努力推動患者尋求 Moderna 的 COVID 疫苗。正如我之前提到的，我們希望為今年秋天已經一起接種季節性流感疫苗的消費者簡化體驗。我們為這個秋季充滿活力。

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.

轉到幻燈片 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 2024 年推出的 RSV 疫苗感到興奮，商業團隊正在開展一系列活動，以確保我們盡快開發出我們希望在該市場佔據很大份額的產品。通過在主要醫學會議上生成和展示我們 III 期研究的詳細數據，我們已經提高了人們對 RSV 的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更多數據，表明疫苗效力在所有接受測試的年齡組以及患有既往合併症的參與者中始終保持高水平。幻燈片右側的數字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，付款人和主要意見領袖對我們的數據的反饋以及我們的 mRNA 平台在預防 RSV 方面的應用讓我們感到鼓舞。

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，以確保在發佈時可以訪問。商業團隊活躍在當地市場，為 2024 年的商業發布做準備。具體來說，我們正在建設我們的數字能力，以便我們能夠在疫苗獲得批准後立即有效地對客戶進行教育。當我們投資於啟動前活動時，我們已經開始製造疫苗和預裝注射器的組件。我們對將投放到這些大型呼吸系統市場的產品的概況感到興奮。

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.

正如我們在疫苗日討論的那樣，估計我們的 3 種主要呼吸道疫苗的總潛在市場是巨大的。 COVID、RSV 和流感分別提供 150 億美元、60 億至 80 億美元和 60 億至 90 億美元的潛在潛在市場。我們相信我們可以在這個價值約 300 億美元的呼吸系統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 RSV 和流感做準備。我們相信，我們在呼吸系統市場的機會將繼續擴大到 2024 年以後，我們的下一代疫苗，重要的是，未來的聯合疫苗，將使我們的市場份額超過時間。

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.

現在轉到幻燈片 29，我想與您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設置中符合條件的患者群體。我們已經與我們的合作夥伴默克公司一起宣布，我們將開始輔助黑色素瘤和輔助非小細胞肺癌的 III 期試驗。在這 2 個適應症中，美國和歐洲每年有超過 130,000 名新患者。

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我們的臨床團隊密切合作，以確定個體化新抗原治療對可尋址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，在這個領域中，我們在癌症需求未得到滿足的領域為一名患者提供一種藥物。鑑於個性化的方法，我們正在重新構想我們的商業模式，以及我們的合作夥伴，以及端到端的患者護理旅程。

With that, I will turn it over to Jamey.

有了這個，我會把它交給 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度的財務業績，回顧我們 2023 年財務展望的框架，並簡要回顧一下我們最近的疫苗日演講。轉到我們的第一季度業績，從幻燈片 31 開始。

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.

產品總銷售額同比下降 69% 至 18 億美元，2023 年的下降符合我們的預期，主要是由於銷量較上年下降所致。 2023 年第一季度的銷售成本為 7.92 億美元，除了我們單位驅動的製造成本外，這還包括 8600 萬美元的特許權使用費和以下費用： 1.48 億美元用於與過剩和過時的 COVID-19 產品相關的庫存減記，未使用的製造能力為 1.35 億美元，確定採購承諾和相關取消費用的損失為 9500 萬美元。除特許權使用費外，這些費用是由與產能過剩相關的成本和主要來自低收入國家的總體需求預測下降所驅動的。

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 年第一季度為 17%。這一增長是由於上述費用導致的，與上一年相比產品銷售額下降，以及由於我們轉向更小的劑量瓶而製造成本更高作為吸收固定製造成本的較低產品銷售額。

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 CMVThanks, 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.

研發費用為 11 億美元，比上年增長 104%。研發支出的增加繼續受到臨床試驗相關費用的推動，特別是我們針對 RSV、季節性流感和 CMV 的 III 期研究。謝謝，Arpa，大家好。今天上午，我將介紹我們第一季度的財務業績，回顧我們 2023 年財務展望的框架，並簡要回顧一下我們最近的疫苗日演講。轉到我們的第一季度業績，從幻燈片 31 開始。

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.

產品總銷售額同比下降 69% 至 18 億美元，2023 年的下降符合我們的預期，主要是由於銷量較上年下降所致。 2023 年第一季度的銷售成本為 7.92 億美元，除了我們單位驅動的製造成本外，這還包括 8600 萬美元的特許權使用費和以下費用： 1.48 億美元用於與過剩和過時的 COVID-19 產品相關的庫存減記, 未使用的製造能力為 1.35 億美元；以及 9500 萬美元的確定購買承諾和相關取消費的損失。除特許權使用費外，這些費用是由與產能過剩相關的成本和主要來自低收入國家的總體需求預測下降所驅動的。

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 年第一季度為 17%。這一增長是由於上述費用導致的，與上一年相比產品銷售額下降，以及由於我們轉向更小的劑量瓶而製造成本更高作為吸收固定製造成本的較低產品銷售額。

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.

研發費用為 11 億美元，比上年增長 104%。研發支出的增加繼續受到臨床試驗相關費用的推動，尤其是我們針對 RSV、季節性流感和 CMV 的 III 期研究。

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.

研發的增加也歸因於員工人數增加以及我們最近宣布與 Life Edit 和 Generation Bio 的合作協議導致的人員相關成本增加。

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.

SG&A 費用為 3.05 億美元，同比增長 14%。支出增長的主要原因是對人員和外部服務的持續投資，以支持我們銷售的產品和相關的商業化活動以及我們的公司擴張。

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.

第一季度的所得稅撥備淨收益為 3.84 億美元，這得益於我們的全年展望，其中包括國際撥備、研發信貸和非經常性項目。淨收入為 7900 萬美元，而去年的淨收入為 37 億美元。稀釋後每股收益為 0.19 美元，而 2022 年第一季度的稀釋後每股收益為 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.

與 2022 年第四季度末的 182 億美元相比，我們在第一季度末的現金和投資為 164 億美元。減少的原因是我們交付預付款產品和股票回購活動導致現金存款減少。用於未來產品供應的現金存款從 2022 年底的 26 億美元下降到 2023 年第一季度末的 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.

現在轉到幻燈片 33。我想介紹一下我們在資本配置優先事項方面取得的最新進展。我們的首要投資重點已經並將繼續在多個領域對基礎業務進行再投資。如前所述，第一季度的研發支出同比增長 104%，我們繼續預計 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.

正如我們在疫苗日的演講中所討論的那樣，這筆投資的大部分用於我們的呼吸道疫苗特許經營權，我們預計這將在相對較短的時間內產生可觀的回報。我們還投資於我們的數字能力。該組織的商業擴張以及擴大我們的製造足跡。隨著我們擴大國際和美國製造足跡，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。正如之前宣布的那樣，我們在第一季度成功完成了對 OriCiro 的收購，業務整合正在順利進行。此外，我們在本季度與 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，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後，我們會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 萬股股票。截至 2023 年 3 月 31 日，我們還有 23 億美元的股票回購授權。

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.

現在讓我們轉到幻燈片 34 上更新的 2023 年財務框架。我們繼續就 2023 年交付的約 50 億美元的 COVID 疫苗銷售達成提前採購協議。我們正在積極談判美國的商業市場和政府合同以及其他日本、歐盟和其他主要市場的合同。我們繼續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.

由於我們呼吸業務的季節性，我們預計第二季度的銷售額為 2 億至 3 億美元。我們繼續預計 2023 財年報告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，然後在下半年降低我們的平均水平。

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 SG&A，我們繼續預計全年支出約為 60 億美元，其中研發費用約為 45 億美元。在研發信貸、國際規定和非經常性項目的推動下，我們現在預計全年稅收優惠將達到 3 億至 5 億美元。最後，我們繼續預計資本支出約為 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 Stephane 之前，對於那些無法參加或沒有看過我們疫苗日演示文稿的網絡廣播的人，我想快速回顧一下財務要點。鑑於目前對我們的呼吸系統特許經營權進行了大量投資，我們希望列出我們設想的到 2027 年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.

回到 Arpa 結束她早先言論的地方，我們相信 COVID、RSV 和流感的市場規模到 2027 年將超過 300 億美元，我們預計將在這個市場中佔據 80 億至 150 億美元。雖然隨著我們從大流行環境過渡到流行環境，短期內我們的商品銷售成本百分比將保持高位，但我們認為到 2027 年這應該會正常化到 20% 到 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.

我們還制定了未來 3 年所需的 60 億美元至 80 億美元的累計研發投資，然後到 2027 年正常化為 10% 的呼吸道疫苗收入的常規維持量。最後，我們喜歡呼吸道疫苗特許經營的特點，鑑於高度靈活的成本基礎、低資本密集度、持久的未來收入和高潛在回報，這可能導致每年 40 億至 90 億美元的自由現金流，並具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，我現在將把電話轉回給斯蒂芬。

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 Jamey、Arpa 和 Stephen。在我們結束問答環節之前，讓我分享一些想法。隨著幾個開發項目的實現，這不是另一個有希望的商業前景。在 COVID 中，我們正在完成與客戶的討論。而且我相信我們會在美國、日本和世界各地看到 23 年秋季的大量額外合同。

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，各國政府正準備在秋季開展疫苗接種活動。我很高興我們已經開始預發布市場開發和 RSV 的風險製造，我們預計將在 24 年推出。在腫瘤學方面，該團隊正在取得長足進步。我們預計將在 2023 年剩餘的 8 個月內實現我們開發管道的關鍵里程碑。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 毒株的方向，我們預計將在 2023 年秋季推出更新的 COVID-19 疫苗。 23.

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.

我們計劃申請批准 RSV 疫苗，303 期流感研究應該在今年夏天之前全部註冊，我們預計第四季度會有數據。對於 INT 癌症治療，我們希望進行額外的 II 期更新，啟動我們在輔助黑色素瘤中的 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。我們在 5 月 18 日提供 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.

這對我們 Moderna 來說是一個非常激動人心的時刻，我要感謝我們的團隊的辛勤工作和對我們使命的承諾。我們的平台正在全力以赴。在傳染病疫苗中，查看呼吸、潛伏和現在進入細菌疫苗的數據和組合。對 INT 的現狀和發展方向感到非常興奮。罕見疾病 PA 緊隨其後的是 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關鍵更新。 9 月 13 日，我們在那裡進行年度研發。我們將展示新的開發管道數據，並在 12 月 7 日舉辦第二個年度 ESG 日。我們相信，我們在所有模式中取得的令人難以置信的進步，使我們的公司能夠取得長期的財務成功。但我們公司的使命是激勵我們整個團隊每天上班，為 mRNA 醫學帶來最大可能的影響。

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，可以消除或大大減少由呼吸道病毒、潛伏病毒、細菌、癌症、調節疾病和越來越多的其他疾病引起的人類痛苦。我們致力於在未來幾年內將一些更有前途的技術推向市場，並已發佈到 COVID 以完成我們的使命。

With this, we'll take questions. Operator?

有了這個，我們會提出問題。操作員？

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

（操作員說明）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 2 個快速問題。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？這兩組之間的定價如何？您什麼時候開始看清實際合同和訂單？然後我的第二個快速問題是關於您對 PCV 程序的 ASCO 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。所以我將從前 2 個關於商業的問題開始，然後將其交給 Stephen 討論 ASCO。就整個美國市場的定價而言，我們確實預計更新疫苗後的標價將在 110 到 130 之間。如您所知，在商業市場上，我們將提供不同的差異化折扣付款人類型，從政府機構到商業參與者。

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.

在訂單時間方面，我們正在積極與美國客戶進行談判。我們在兩個方面受到很大鼓舞。首先，我們的客戶確實理解並理解 COVID 持續成功所帶來的重大健康負擔。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治療和嚴重疾病的侵害。

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.

在與不同客戶的對話中，如果他們欣賞並認可（聽不清）背後的完整真實世界證據以及我們疫苗的有效性和概況，我們繼續受到鼓舞的另一件事。因此，我們預計在接下來的 4 到 6 週內，我們將開始看到收縮情況更加明朗，這種情況將持續到第二季度末和第三季度初。

(Operator Instructions)

（操作員說明）

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？好的。對不起。 Gena（聽不清）在 ASCO 上發表演講。所以是斯蒂芬。正如我所說，將共享 2 個演示文稿和 2 組數據。第一個將集中在無遠處轉移生存，DMFS。如您所知，DMFS 是總體存活率和遠處轉移的另一個替代指標，不幸的是，它通常是內臟轉移，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 期研究的方案包括在第一次分析、初步分析中，同時著眼於 RFS 和無遠處轉移生存，DMFS 是次要終點，我們將在 ASCO 上首次展示這些數據。將以海報形式共享的第二個數據將是一些關於生物標誌物的數據和關於跨人群 INT 表現的額外數據。對於那些對此感興趣的人來說，這些數據將更多地進入基礎科學，但我們將研究產品的作用機制以及進一步的風險分層，我們相信這會提供更多的信心，我們的信號在 II 期研究中看到 INT 的潛在利益是有彈性的，確實預示著未來的好兆頭。

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，您能為我們構建一下嗎？我想在過去，當你在這裡查看主要失代償事件的相對風險降低以及從 MMA 和 GSD1a 和 OTC 到你的整體罕見疾病專營權的可轉化性時，你已經談到 25% 具有臨床意義。然後是 COGS 的第二個問題，您如何看待 2023 年以後的情況？考慮到您在展望 2027 年時所假定的呼吸系統特許經營收入的市場份額，您如何看待這種 OpEx 支出的盈利能力，包括您的研發和 SG&A 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.

感謝你的提問。所以我會先把罕見病部分放在 PA 上。因此，正如我們去年 9 月分享的那樣，我們在去年 9 月的幾個劑量水平後對 PA 研究進行了數據截斷。我們看到代謝失代償率降低了 50% 以上。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 上分享的是對此的進一步更新。因此，這將是三月份的數據截止日期。大約還有 6 個月，其中還包括至少 6 個月的第三劑量水平、0.5 mpk 和下一個劑量水平的一些其他新出現的數據。同樣，我不想提前分享這些數據。但是，當然，我們將關注這種益處的強度，隨著劑量的增加，我們希望 MDE 發生率降低 50%，MDE 降低約 50%。

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.

而且我們還希望清楚地看到該藥物繼續具有很好的耐受性，並且在該患者群體中沒有安全問題。就整個研究的藥物總時間而言，我們還將看到更多的隨訪時間，這將有助於推進該案例。

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.

現在就與其他項目的關係而言，丙酸血症 PA 是甲基丙二酸血症 MMA 的姊妹病。隨著我們對我們正在擴展 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，我們確實相信它會非常直接地讀入我們希望很快看到的數據在綜合格鬥中。我們已經開始看到來自 II 期——I/II 期人口研究的一些數據。

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.

我會提醒您，MMA 也在患者體內長期服用，並通過劑量水平逐步增加。在適當的時候，我們顯然也希望在 MMA 方面提供有關該數據的更新，但我們確實相信 PAD 會通過它取得真正積極的成果。一般來說，我會說我們的肝臟代謝罕見疾病項目是這樣的，包括 OTC 和你提到的其他項目。

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，今年是銷售額的 35% 到 40%。正如你提到的，到 2027 年我們將達到 20% 到 25%。所以我不確定這是一條完美的直線，但讓我給你一些會隨著時間的推移而改善的因素。

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.

首先是體積。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給我們帶來更好的影響力。我認為可預測性對此有所幫助，因此今年是一個非常不為人知的季節。這將是我們第一次過渡到地方病。因此，隨著時間的推移，這將變得更加可預測。我認為 ASP 也會繼續上漲。隨著時間的推移，更大的單劑量文件或 PFS 演示可能會抵消一點，我們已經為 2023 年制定了一些預算。所以總的來說，我們有信心降低我們的庫存水平並整體降低我們的成本作為銷售額的百分比。

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.

由於它涉及 2027 年損益表以及這對公司整體盈利能力意味著什麼，我們尚未就此發布任何指導。我想對那些聽到我準備好的發言的人重申，呼吸道疫苗業務應該產生 40 億至 90 億美元的收入，我們在頁面上列出了這一點。老實說，然後我們只需要看看。我們有一個令人興奮的管道。我們必須了解 INT 發生了什麼。我們對此感到非常興奮，包括罕見病和潛在疾病，我們會為所有利益相關者做最好的事情。因此，如果繼續將這些利潤中的一部分重新投資到業務中是有意義的，我們就會這樣做。我們只需要坐等，看看當時管道的樣子。

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

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

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?

這是泰勒的塔拉。所以我知道你提到了一些關於時間的問題。但具體來說，我們想知道的是，一旦為下個月的秋冬季節選擇了 COVID 毒株，您認為完成美國和國外的商業合同大約需要多長時間？然後在美國之外，最近關於與輝瑞和歐洲正在進行的談判的公告是否真的為你們創造了一個機會，或許可以在歐洲推動比先前預期更大的合同？

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.

感謝你的提問。你的第一個問題是關於在美國簽訂合同的時間。在我們等待 6 月中旬選擇最終變體菌株的同時，我們已經根據 FDA 選擇的變體啟動了合同對話。因此，正如我之前提到的，我們確實預計在接下來的幾週內會簽署其中一些合同，直至第三季度。因此，這將是一種基於客戶的不斷發展的時間表。

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，歐盟正在與輝瑞重新談判的消息令我們感到鼓舞。對我們來說，歐盟可能不想依賴單一供應商的信號。我們也感到鼓舞的是，歐盟確實認識到我們 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，看看我們如何能夠幫助保護歐盟 1.4 億左右處於 COVID 感染高風險中的人。當我們獲得歐盟談判的最新信息時，我們也將分享這些信息。

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.

關於 PCV 或者我應該說，INT 癌症治療我想問的兩個領域。斯蒂芬，你在幻燈片中談到並提到了時間以及突破性指定。我想你提到過你確實與 FDA 就你最近的數據進行了討論。你能談談圍繞潛在加速批准的情景，你必須盡快將其帶給患者的論點，或者我們真的需要等待數年才能運行 III 期嗎？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?

然後第二個問題，我認為，對於 RSV 也很重要。顯然，我們希望看到收入多樣化。這可能會在明年到來。您如何看待 2024 年的收入機會？那是一場付款人之戰還是那裡的幾個競爭對手，你的優勢在哪裡？您如何看待明年的市場份額和收入？

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.

邁克，謝謝你提出這個問題。我會拿 INT 的。所以看，我認為關於如何將這種藥物帶給患者的討論顯然還處於早期階段。即使在 II 期研究中，雖然數據確實令人興奮，但現在說它足以——在這一點上直接進入加速批准可能還為時過早。但我們認為明年或幾年的某些情況可能會導致我們和監管機構考慮這一點。

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.

短期來看，數據還是成熟的。我們還沒有公佈遠處轉移的無生存數據。我們將在 ASCO 這樣做。我們顯然很高興分享這些數據，它開始構建更完整的圖片和 DMFS，因為它著眼於內髒病變，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.

我們在 ASCO 演示文稿中也有額外的生物標誌物數據。這兩個數據集都在處理初始分析，即 40 個事件。但我要提醒你，我們對 51 個事件進行了分析，我們認為這些曲線會更加成熟。顯然，我們還沒有越過那個。當我們觸發該分析的 51 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。這將是我們理解的一個時間點，比方說，該研究的總隨訪中位數超過 2.5 年，也許是 3.5 年。整體曲線是什麼樣的？風險比是多少？周圍的統計數據如何？然後我們從我們已經完成的所有正在進行的生物標誌物工作中了解到更多關於 MOA 的信息。因此，我認為更豐富的數據集確實是我們正在等待看到的。

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，還有第二個部分，那就是。任何關於加速批准的考慮，無論是針對 INT 還是更一般的，越來越多地取決於您是否啟動了驗證性研究，這是否合適。因為我們都看到了開始大量註冊驗證性研究實際上如何幫助確保答案很快就會出現，並且加速批准可以轉換為完全批准或根據這些驗證性結果進行調整。我們非常適應這一點。因此，在我們等待 II 期數據成熟的同時，我們現在的主要重點是確保我們支持 III 期研究並儘快將其納入。

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.

我認為我們可能會在未來某個時候考慮與尋求加速批准的監管機構合作和討論的條件，屆時該 III 期研究正處於被納入的道路上，顯然尚未宣讀，但很好那裡正在註冊的路徑以及我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收益的步伐，也許即使在患者人群中，從我們分享的分層角度來看，他們也處於更高的風險中今天的一些數據。那些 - 補充這些因素將觸發一個機會，說現在是時候在等待確認讀出的同時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。所有這些事情仍然必鬚髮生。所以這就是為什麼現在我們的重點是開始 III 期，讓它註冊並繼續在隨機的 II 期研究中關注這個非常有趣的故事。

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 問題。我們仍然對我們（聽不清）RSV 的機會感到非常興奮。當我們查看 III 期耐受性和有效性數據時，我們疫苗的概況使我們處於競爭格局的高端。從安全的角度來看，迄今為止，我們還沒有發現任何神經不良事件，而且我們的嚴重不良事件在兩組中也很平衡。

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.

這對 2024 年意味著什麼，因為我們將 RSV 視為季節性業務，我們確實預計每年都會在美國進行談判。維修將有機會繼續審查跨多個參與者的數據，我們將積極努力在美國商業市場定位自己。

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。我只是想知道在 INT 上，您是否可以對那裡的肺部 III 期設計發表評論。那麼，是什麼促使這種信心在這一點上向前邁進呢？您能否提醒我們您目前在這方面的任何數據？

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。所以這是兩件事。所以首先，我們確實研究了非小細胞肺癌的 I 期，其中有患者。那些不是輔助患者，但儘管如此，確實有一些數據、生物標誌物數據和其他臨床歷史，同樣，不是來自第一階段的對照研究。我認為另一個信心是我們正在採取的行動機制的力量在我們已經進行的 II 期研究中看到並跨風險層進行轉化，真的，我們認為當你更廣泛地看待輔助適應症時設置得很好，這就是輔助非小細胞肺癌，甚至新輔助非-從可譯性的角度來看，小細胞肺癌很有意義。因此，它結合了 I 期的一些數據。我們在黑色素瘤的 II 期看到的表現的廣度和強度，顯然，在 PD-1、PD-1/L1 治療中學到了什麼輔助設置更廣泛。

Our next question comes from Jessica Fye with JPMorgan.

我們的下一個問題來自摩根大通的 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?

對已經提出的一些問題進行一些跟進。首先，關於秋季的美國 COVID 合同，我們是否應該期待更新，因為這些更新是實時完成的，或者更像是一種組合狀態報告，例如，第三季度初的第二季度結果。其次，隨著 COVID 進入流行階段，您是否看到在美國以外（例如歐洲）提高 COVID 疫苗價格的機會？最後，關於 RSV，您認為需要多快批准 RSV 才能讓您參與 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。關於為美國商業合同提供更新的第一個問題，我們目前不承諾對每份合同進行實時更新。但至少，我們將在季度電話會議上就我們與美國商業合同的進展情況提供更新。第二個問題是關於美國以外的定價，我們不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，我們仍然主要採用中央政府採購模式。因此，我們還沒有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 RSV 合同的。我們的目標是在 2024 年推出 RSV，我們將繼續研究美國市場的合同細節。但根據我們目前的假設，假設 2024 年推出，我們確實相信我們將及時簽訂合同，於 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.

也許您可以詳細說明一下您對針對流感 B 型毒株的更新配方的信心。如果這是研究更高的絕對劑量，您是否可以評論劑量水平。也許只是就這種化合物而言，但在流感平台方面也更廣泛，因為你添加了額外的抗原，只是你對反應原性的看法嗎？然後從廣義上講，添加這些化合物（聽不清）？其次，就在 RSV 中，只是一些內務處理。我猜，你還打算在這個季度提交文件嗎？

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.

首先是流感問題。因此，我們顯然已經從 P302 研究中獲得了免疫原性數據，這些數據表明我們已經達到了非劣效性，或者被認為對 B 菌株具有非劣效性。即使在北半球，這項研究也在進行中。因此，我認為即使在我們為當前 III 期研究改進 B 菌株更新之前，我們對能夠清除該標準的信心很高，並且得到了數據的支持。

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。我們現在在使用 COVID 和其他更新我們的抗原和疫苗方面有很多經驗。因此，我們將期待 P303 中的數據。但我認為我們相信我們會比剛剛在非劣效性 P302 研究中做得更好，我們希望看到我們將取得一些可能趨向於優勢的成果。但這不是這項研究的具體目標。就反應原性和劑量而言——我只想說我們沒有改變這項 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管道的反應原性時，我們有大量的候選疫苗和疫苗，我們的劑量大大高於 50 微克。即使在流感研究中，我們也根據之前分享的數據做到了 100 微克。我們相信，有些人群的效果很好。事實上，有像我們的 RSV 疫苗這樣的疫苗，50 微克的耐受性非常好。迄今為止，我們對該配置文件感到非常滿意。

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個疫苗案例的疫苗。你不能看劑量再決定。當我們開始進行組合時，我們將優化反應原性，該疫苗的耐受性與我們希望提供的高功效方面的好處相比，通常是通過這些組合研究中的免疫反應來衡量的。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 的劑量水平降低 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.

現在在 RSV 上，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。這包括我們希望將該產品商業化並在明年推出的所有市場。當然，當我們進入這些監管時，我們會隨時對您進行評估——我們正常的季度更新中的監管流程。

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，我認為你一直在強調機會輔助和新輔助設置。但是，我想知道您是否可以評論一下轉移設置中的計劃，是否有 INT 轉移設置的位置？也許與此相關，您是否計劃更新我們在 2021 年 50 日看到的轉移和下一個癌症數據集？那裡的任何顏色都非常受歡迎。

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。謝謝你提出這個問題。所以我認為我們確實認為 INT 在使用方面可以更早也可以更晚。這是一個具有挑戰性的問題，即我們在短期內優先考慮哪一個。我認為我們認為，我們相信，在佐劑方面存在巨大的機會。那是您聽到我們當前所有活動的地方。這是我們的重點。這就是我們試圖進入關鍵研究的地方，非常非常快地進入 III 期研究。但是，如果您尋求輔助治療，我們確實有輔助治療經驗。您指向頭部和頸部數據。我們也有來自第一階段的體細胞黑色素瘤，實際上有一些佐劑——抱歉，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有一定的障礙。事實上，一般來說，免疫療法在晚期疾病中一直舉步維艱，而該技術的真正力量、其安全耐受性、潛在益處可能處於上游階段。因此，當我們密切關注轉移空間時，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.

當然，我們現在正在等待更多數據來決定我們是否要在短期內與我們的合作夥伴默克公司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。目前傳統上不使用免疫療法的疾病，但我們是一種像 INT 這樣耐受性良好的方法，我們認為它確實可以增強針對癌症的特定 T 細胞反應，這可能具有獨特的好處。再一次，這是我們渴望在短期內與我們的合作夥伴默克公司探索 INT 方法的地方。

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.

我們目前沒有在這兩個領域投入大量精力，但我們可以很快轉向。所以現在，我們關注的是佐劑的關鍵研究，我們正在密切關注轉移數據的演變，我們正在嘗試考慮如何將生物標誌物啟用或以其他方式轉移到更早的階段-stage 疾病，我相信如果 INT 有可能獲益，我們將找到探索所有這些領域的方法，然後現在就是盡快抓住機會的問題。

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。您最早什麼時候可以在市場上擁有 COVID 和流感組合的潛力？

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.

我會很快評論（聽不清），但是聯合疫苗——所以第一點是我們需要批准流感。我想在疫苗日，我們談到了我們的期望，我們希望在 2025 年批准並推出 COVID-flu 組合。

Our next question comes from Geoffrey Meacham with BoA.

我們的下一個問題來自 BoA 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?

這是傑夫·米查姆的亞歷克斯·哈蒙德。因此，鑑於您的臨床管道的廣度和新疫苗的潛在機會，Moderna 如何確定要追求的資產或適應症的優先級？一旦（聽不清）假設其萊姆病的概念得到證明，您在針對其他細菌適應症方面的臨床策略是什麼？最後，您如何考慮 INT 計劃的資本部署？

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.

我先回答第一個問題。我想我會參加所有 3 個，但我邀請我的同事也進來。所以首先是我們如何看待機會。這是我們面臨的一個巨大挑戰。當我們過渡到整個管道的患者群體或關鍵研究時，我們顯然看到了非常高的成功率。它的簡短版本是我們尋找我們認為我們的技術通過其模式得到很好驗證的地方。因此，我們在下一個適應症以及該適應症中存在大量未滿足需求的地方取得了很高的、有希望的差異化成功。

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，通常在醫療保健系統方面也存在大量未滿足的財務需求，而這最終是我們想要為其提供的價值。這就是我們處理它的方式。那可能是傳染病。這就是我們考慮擴大我們的呼吸專營權的方式。這就是我們考慮擴大潛在特許經營權的方式。我們在那裡建立。正如我們已經在做的那樣，你將看到我們在罕見疾病領域所做的是與我們開始在罕見代謝疾病領域看到概念證明一樣的擴展。

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，你問了一個關於 INT 的問題，也許我會跳到你問題的第三部分，即我們如何考慮 INT 方面的資本分配。很少有什麼比癌症具有更大的疾病負擔、社會成本——發病率和死亡率的經濟成本。我們確實相信 INT 有潛力成為該領域的變革性治療。因此，我們必須弄清楚我們如何負責任地、積極地在我們認為 INT 可以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.

現在我們在這項工作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，他對此有高度的信念，正如我們所談到的那樣，我們正在與他們共同投資。因此，從資本配置的角度來看，我們開始一起研究 INT 腫瘤學中存在機會和未滿足需求的跡象。

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，現在的重點是輔助治療，但當然，我們也會關注轉移性和早期疾病。最後一個問題，我想我要解決的是中間一個問題，即我們如何看待萊姆 POC 以及它在細菌方面的作用是什麼。我認為我們非常熱衷於解決萊姆病問題，因為與萊姆病相關的需求未得到滿足，尤其是在北部——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，展示一種細菌 - 抗菌疫苗接種是一件非常有趣的事情。我們已經有了一個重要的發現渠道來研究其他細菌，如果我們能夠在萊姆中展示概念驗證，我們將很快提出來。我不會提供有關這些特定目標的更新，因為這仍處於臨床前研究階段。但請放心，我們在細菌方面的方法將類似於我們在呼吸系統疾病、潛伏疾病、INT 或罕見疾病方面的方法，正如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概率很高的其他項目。

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 Simon Baker 和 Redburn。西蒙，你的線路是開放的。你可以問你的問題。

Did you want me to remove Simon from the queue?

你想讓我把 Simon 從隊列中移除嗎？

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

是的，您可以轉到下一個問題。這將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 Hartaj Singh 和 Oppenheimer。

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.

這是今天 Hartaj 的 Eka。因此，在幻燈片中，您提供了估計的 2027 年呼吸產品銷售範圍，高端幾乎是兩倍或更低。我很好奇你能否談談呼吸道疫苗的獨立份額與組合份額在多大程度上影響這個收入範圍，我們只是想了解這種感覺——組合疫苗對類似市場的蠶食程度？其次，關於兒科 RSV 計劃的問題。因此，由 RSV 引起的兒童疾病負擔非常高。您能否談談您在兒科 RSV 項目競爭背景下的進展以及潛在的開發時間表？

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。我將從關於呼吸機會的第一個問題開始。我們聽到消費者和我們的客戶群組合疫苗都表現出極大的熱情。我們相信，通過將這 2 種，可能是 3 種疫苗合併為 1 種疫苗，將提高依從性和依從性，以解決廣泛的呼吸道疾病負擔。因此，當我們考慮商業機會時，我們確實認為組合將是大部分機會，因為我們展望 2027 年，我們確實預計單一療法會被蠶食。

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，隨著我們隨著時間的推移不斷改進我們的產品，特別是在流感和 COVID 方面，我認為毒株匹配得越好，療效越好，我認為，這也會在未來對我們有利。

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.

和兒科 RSV 問題。因此，只要我們從事 RSV 研究，我們實際上就一直在研究兒科 RSV。因此，我們正在進行臨床試驗，包括針對影響該人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需求和領域。在指導未來的時間安排方面，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.

我們將提供我們看到的數據更新。實際上，我們已經分享了我們儿科項目的一些早期數據。兩者都會呈血清陽性。因此，以前感染過 RSV 的孩子會有一些好處。人們——那些孩子確實會再次感染。這看起來更像是一組促進研究。然後會有血清反應陰性的孩子。這些地方可能存在最高未滿足的需求，那些還沒有第一次感染 RSV 的人，所以非常年幼的孩子到 1 歲。隨著時間的推移，你可能會看到我們做的是將這些發展計劃分開因為它最終會截然不同——目標人群。更有可能的是，血清反應陽性者移動得更快，而血清反應陰性者移動得更慢，這通常是兒科發育的情況。

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 以聽取任何結束語。

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，謝謝大家今天加入我們並提出您的問題。下個月將是令人興奮的。 PA 數據，5 月 18 日和俄勒岡州 ASCO 的新 INT 數據。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。您現在可以斷開連接，並度過美好的一天。