莫德納 (MRNA) 2023 Q4 法說會逐字稿

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

美好的一天，感謝您的支持。歡迎參加 Moderna 2023 年第四季電話會議。 （操作員指示）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.

現在我想將會議交給今天的發言人拉維娜·塔魯克達爾 (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 fourth quarter and full year 2023 financial results and business updates. You can access the press release issued this morning as well as the slides that we'll be reviewing by going to the Investors section of our website.

謝謝你，凱文。大家早安，感謝您參加今天的電話會議，討論 Moderna 第四季度和 2023 年全年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審查的幻燈片。

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

參加今天電話會議的是我們的商務執行長 Stéphane Bancel；史蒂芬‧霍格，我們的總裁；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. 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.

在我們開始之前，請注意，本次電話會議將包括根據1995 年《私人證券訴訟改革法案》的安全港條款做出的前瞻性陳述。請參閱隨附簡報的幻燈片2 以及我們向SEC 提交的文件，了解以下重要風險因素：可能導致我們的實際表現和結果與這些前瞻性陳述中明示或暗示的表現和結果有重大差異。

With that, I'll turn it over to Stéphane.

這樣，我就把它交給 Stéphane。

Thank you, Lavina. Good morning or good afternoon, everyone. Thank you for joining us today. I will start with a review of 2023. Jamey will then present our financial results. Stephen will then review our late-stage clinical programs, and I will close by sharing our 2024 priorities.

謝謝你，拉維娜。大家早安或下午好。感謝您今天加入我們。我將首先回顧 2023 年。然後 Jamey 將介紹我們的財務表現。然後，史蒂芬將回顧我們的後期臨床項目，最後我將分享我們 2024 年的優先事項。

Let me start with our mission: Moderna's commitment to deliver the greatest possible impact to people through mRNA medicines. In 2023, every member of the Moderna team helped to advance our mission, which is a driving force that motivates our team every single day. We impacted more than 100 million people around the world, and we advanced our development pipeline across all of our franchises, including infectious diseases, oncology and rare disease.

讓我從我們的使命開始：Moderna 致力於透過 mRNA 藥物為人們帶來最大的影響。 2023 年，Moderna 團隊的每一位成員都幫助推動我們的使命，這是每天激勵我們團隊的動力。我們影響了全球超過 1 億人，並推進了我們所有特許經營業務的開發管道，包括傳染病、腫瘤學和罕見疾病。

2023 was a difficult year as we transition from a pandemic to a seasonal endemic market. We reported sales of $6.1 billion for 2023, which was at the low end of our financial framework range. These sales exclude the recognition of $600 million of deferred revenue from Gavi.

2023 年是艱難的一年，我們從疫情市場過渡到季節性流行市場。我們報告的 2023 年銷售額為 61 億美元，處於我們財務框架範圍的低端。這些銷售額不包括 Gavi 確認​​的 6 億美元遞延收入。

In the U.S., the vaccination rate was down year-over-year. We were pleased that our U.S. commercial team drove an increase in our retail market share from 37% to 48%. Outside of the U.S., we were not able to compete in the EU market in the second half of 2023 due to a competitor contract, and our performance led to a low market share in Japan. We did have a strong performance in Israel, Switzerland and Taiwan.

在美國，疫苗接種率年減。我們很高興我們的美國商業團隊推動我們的零售市場份額從 37% 增加到 48%。在美國以外，由於競爭對手的合同，我們無法在 2023 年下半年在歐盟市場競爭，而且我們的表現導致在日本的市場份額較低。我們在以色列、瑞士和台灣確實表現強勁。

We took several important actions in 2023 that we set our commercial COVID business up for success. We resized our manufacturing footprint, which has been established to support capacity at pandemic levels. We exited contract manufacturing relationships and reduced inventory levels. These initiatives will improve cash flow from our COVID business moving forward.

我們在 2023 年採取了多項重要行動，為我們的商業新冠疫情業務取得成功奠定了基礎。我們調整了製造規模，其建立是為了支持大流行水準的產能。我們退出了合約製造關係並降低了庫存水準。這些措施將改善我們未來新冠疫情業務的現金流。

We also flattened the commercial structure. All regions report directly to me now for more targeted sales execution and also a better integration with global teams. We focused our R&D spending and our SG&A expenditures towards near-term growth and higher return on investment projects.

我們也扁平化了商業結構。現在，所有區域都直接向我匯報，以實現更有針對性的銷售執行，並更好地與全球團隊整合。我們將研發支出和銷售、一般管理支出重點放在短期成長和更高的投資項目回報。

While sales were challenging in 2023, our development team had a great year, with excellent progress across many of our late-stage pipeline programs. In 2023, we advanced our pipeline and now have 9 late-stage programs. Let's start with respiratory vaccine.

儘管 2023 年的銷售面臨挑戰，但我們的開發團隊度過了美好的一年，我們的許多後期管道專案都取得了出色的進展。 2023 年，我們推進了研發管線，目前有 9 個後期專案。讓我們從呼吸道疫苗開始。

For RSV, we filed for approvals around the world. We reported positive data from our flu P303 study, and we are fully enrolled in the Phase III studies for our next-gen COVID, mRNA-1273, and flu plus COVID combination vaccine, mRNA-1083.

對於 RSV，我們在世界各地申請了批准。我們報告了流感 P303 研究的積極數據，並且我們已全面參與下一代新冠病毒 mRNA-1273 和流感加新冠病毒聯合疫苗 mRNA-1083 的 III 期研究。

In our latent franchise, we are very excited that our Phase III CMV trial is now fully enrolled.

在我們的潛在特許經營權中，我們非常高興我們的 III 期 CMV 試驗現在已全部入組。

In our individualized neoantigen therapy program, or INT, where we partner with Merck, Phase III studies in adjuvant melanoma and non-small cell lung cancer are enrolled. We purchased and are currently building out a manufacturing site in Marlborough, Massachusetts to enable commercialization of our INT program. Already this therapy programs continue to progress well.

在我們與默克合作的個人化新抗原治療計劃 (INT) 中，納入了輔助黑色素瘤和非小細胞肺癌的 III 期研究。我們在馬薩諸塞州馬爾伯勒購買並目前正在建造一個生產基地，以實現我們的 INT 項目的商業化。該治療計劃已經繼續取得良好進展。

We're in dose selection for the registrational study of our propionic acidemia program. In MMA, we are pleased to see improvement in biomarkers and clinical outcomes.

我們正在為丙酸血症計劃的註冊研究進行劑量選擇。在 MMA 中，我們很高興看到生物標記和臨床結果的改善。

In research, we made 6 external investments, including 1 acquisition, which we expect will increase the strategic reach and also the breadth of our mRNA platform.

在研究方面，我們進行了 6 項外部投資，其中包括 1 項收購，我們預計這將擴大我們 mRNA 平台的策略範圍和廣度。

Now turning to our 2023 financial summary. We reported GAAP revenue of $6.8 billion, a net loss of $4.7 billion, primarily driven by mostly noncash charges of $3.7 billion related to resizing of manufacturing and the tax valuation allowance. We are pleased to end the year with cash and cash investments of $13.3 billion.

現在轉向我們的 2023 年財務摘要。我們公佈的 GAAP 收入為 68 億美元，淨虧損為 47 億美元，主要是由於與製造業規模調整和稅收估價津貼相關的 37 億美元非現金費用所致。我們很高興以 133 億美元的現金和現金投資結束了這一年。

Let me turn to Jamey for more color on the financials.

讓我向 Jamey 尋求更多有關財務狀況的資訊。

Thanks, Stéphane, and hello, everyone. Today, I will review our financial performance for both the fourth quarter and the full year of 2023. I'll also provide our financial framework for 2024. Let me start with a review of our commercial performance this year.

謝謝，Stéphane，大家好。今天，我將回顧我們2023年第四季和全年的財務表現。我還將提供我們2024年的財務框架。讓我先回顧我們今年的商業業績。

In the first half of 2023, we reported product sales of $2.1 billion, with the majority of sales from advanced purchase agreements signed for delivery in 2022 that were deferred into 2023. We do not expect these sales to repeat in 2024.

2023 年上半年，我們報告的產品銷售額為21 億美元，其中大部分銷售額來自於2022 年簽署的預購協議，這些協議被推遲到2023 年交付。我們預計這些銷售額不會在2024 年重複出現。

In the second half of 2023, we recorded $4 billion in sales from seasonal endemic demand, and an additional $600 million from deferred revenue related to Gavi.

2023 年下半年，我們因季節性流行需求而實現了 40 億美元的銷售額，並因與 Gavi 相關的遞延收入而額外獲得了 6 億美元的銷售額。

Sales in the fourth quarter were $2.8 billion, with $0.8 billion in sales in the U.S. and $0.6 billion in Europe and $1.4 billion in the rest of the world, including the deferred revenue from Gavi.

第四季銷售額為 28 億美元，其中美國銷售額為 8 億美元，歐洲銷售額為 6 億美元，全球其他地區銷售額為 14 億美元，其中包括 Gavi 的遞延收入。

For the full year 2023, product sales were $6.7 billion, comprised of $1.7 billion in sales in the U.S., $1.4 billion in Europe and $3.6 billion in the rest of the world, again, including deferred revenue from Gavi.

2023 年全年，產品銷售額為 67 億美元，其中美國銷售額為 17 億美元，歐洲銷售額為 14 億美元，全球其他地區銷售額為 36 億美元，其中還包括來自 Gavi 的遞延收入。

Moving to Slide 10. As mentioned, net product sales were $2.8 billion this quarter, a 43% decrease from last year. This was largely attributable to the anticipated reduction in sales volume, which was partially offset by a higher average selling price. This decrease is indicative of the evolving market dynamics as we navigate the transition of the COVID-19 vaccine market towards a more predictable seasonal pattern like traditional flu vaccines.

轉到投影片 10。如前所述，本季產品淨銷售額為 28 億美元，比去年下降 43%。這主要是由於預期銷量下降，但平均售價上升部分抵消了銷量下降。這種下降表明，隨著我們引導 COVID-19 疫苗市場向傳統流感疫苗等更可預測的季節性模式轉變，市場動態不斷變化。

Cost of sales was $929 million, down from 39% of net product sales in the previous year to 33% this year. This is a demonstration of our strategic efforts in Q3 to resize our manufacturing footprint, which, as expected, led to additional charges in Q4 of $169 million, primarily related to the wind-down of certain contract manufacturing operations. Additionally, cost of sales also includes inventory write-down of $322 million, reflecting revised demand forecasts.

銷售成本為 9.29 億美元，從去年佔產品淨銷售額的 39% 下降到今年的 33%。這證明了我們在第三季度調整製造足跡的戰略努力，正如預期的那樣，這導致第四季度產生 1.69 億美元的額外費用，主要與某些合約製造業務的結束有關。此外，銷售成本還包括 3.22 億美元的庫存減記，反映了修訂後的需求預測。

R&D expenses increased by 16% to $1.4 billion. This uptick reflects our commitment to advancing our late-stage clinical development programs, particularly with our RSV vaccine, CMV vaccine, combination vaccine against flu and COVID-19 as well as our INT program. The increase also included an upfront payment of $120 million associated with the strategic research and development collaboration with Immatics.

研發費用成長 16%，達到 14 億美元。這一增長反映了我們對推進後期臨床開發項目的承諾，特別是我們的 RSV 疫苗、CMV 疫苗、流感和 COVID-19 聯合疫苗以及我們的 INT 項目。此次成長還包括與 Immatics 的策略研發合作相關的 1.2 億美元預付款。

SG&A expenses were $470 million, up 25% year-over-year. The increase in spending was primarily due to the expansion of our commercial operations, particularly in the U.S. market.

SG&A 費用為 4.7 億美元，年增 25%。支出的增加主要是由於我們商業業務的擴張，特別是在美國市場。

Income tax was a benefit of $147 million for the fourth quarter of 2023, largely attributable to the tax benefits as part of finalizing our 2022 U.S. tax return.

2023 年第四季的所得稅收益為 1.47 億美元，這主要歸功於我們最終確定 2022 年美國報稅表所帶來的稅收優惠。

Net income for the quarter was $217 million compared to $1.5 billion in the fourth quarter last year. Diluted earnings per share was $0.55 compared to $3.61 in 2022. We closed the quarter with a strong cash position of $13.3 billion, which is slightly higher than the $12.8 billion we had at the end of the prior quarter.

本季淨利為 2.17 億美元，而去年第四季為 15 億美元。稀釋後每股收益為 0.55 美元，而 2022 年為 3.61 美元。本季結束時，我們擁有 133 億美元的強勁現金頭寸，略高於上一季末的 128 億美元。

Now let's turn to our annual performance on Page 11. Net product sales for the full year 2023 were $6.7 billion, a decrease of 64% from the previous year, mainly due to lower sales volume of our COVID-19 vaccine. As mentioned earlier, this includes the recognition of $0.6 billion from the deferred revenue related to Gavi. Excluding this item, our sales of $6.1 billion were still in line with the framework we provided for the full year.

現在讓我們轉向第 11 頁的年度業績。2023 年全年產品淨銷售額為 67 億美元，比前一年下降 64%，主要是由於我們的 COVID-19 疫苗銷量下降。如前所述，這包括從與 Gavi 相關的遞延收入中確認 6 億美元。排除這項項目，我們 61 億美元的銷售額仍然符合我們提供的全年框架。

Cost of sales for the full year represented 70% of net product sales, a substantial increase from 29% of product sales in 2022. This shift is largely attributable to our strategic efforts to optimize our manufacturing operations, resulting in charges of $1.6 billion and other manufacturing and distribution costs over reduced sales volume. Overall, cost of sales came in at $4.7 billion, slightly below the $5 billion we provided in our latest framework.

全年銷售成本佔產品淨銷售額的70%，比2022 年佔產品銷售額的29% 大幅增加。這一轉變很大程度上歸功於我們優化製造業務的戰略努力，導致產生16 億美元的費用和其他費用。製造和分銷成本超過銷售減少。總體而言，銷售成本為 47 億美元，略低於我們在最新框架中提供的 50 億美元。

Research and development spend was $4.8 billion, and SG&A was $1.5 billion, both in line with our expectations. Our income tax provision was $772 million for the full year 2023.

研究與開發支出為 48 億美元，SG&A 為 15 億美元，皆符合我們的預期。 2023 年全年我們的所得稅撥備額為 7.72 億美元。

During our Q3 earnings call, we discussed the requirement under GAAP to establish a valuation allowance against deferred tax assets when the current year and cumulative income projection for the next 3 years is in a loss position. It's important to note that future income from products not yet approved by regulators are excluded from these income projections, which restricts us to just our COVID vaccine, and it does not include expected future launches. This valuation allowance does not impact future cash flows, future tax returns or the company's ability to utilize deferred tax assets in future periods.

在我們第三季的財報電話會議上，我們討論了根據公認會計原則（GAAP）的要求，當本年度和未來3 年的累計收入預測處於虧損狀態時，應針對遞延稅項資產建立估值準備金。值得注意的是，尚未獲得監管機構批准的產品的未來收入不包括在這些收入預測中，這限制了我們僅生產新冠疫苗，並且不包括預期的未來發布。此估價備抵不會影響未來現金流量、未來報稅表或公司在未來期間利用遞延所得稅資產的能力。

Net loss for the year was $4.7 billion compared to an income of $8.4 billion last year. The decrease in profit was primarily due to lower product sales and higher R&D expenses in 2023. Diluted loss per share was $12.33 compared to the diluted earnings per share of $20.12 in 2022.

今年的淨虧損為 47 億美元，而去年的營收為 84 億美元。利潤下降的主要原因是2023年產品銷售下降和研發費用增加。稀釋後每股虧損為12.33美元，而2022年稀釋後每股收益為20.12美元。

So now let's move to Slide 12. We wanted to provide you additional perspective on our full year financial results by presenting them alongside a summarized version that excludes the impact of the Gavi deferred revenue recognition or resizing charges and the tax valuation allowance. Our total GAAP net loss for the full year was $4.7 billion. However, when excluding these primarily noncash items, the net loss is reduced to $1.6 billion.

現在讓我們轉向投影片 12。我們希望透過將其與排除 Gavi 遞延收入確認或調整費用以及稅務估價津貼的影響的摘要版本一起呈現，為您提供有關我們全年財務業績的更多視角。我們全年 GAAP 淨虧損總額為 47 億美元。然而，如果排除這些主要非現金項目，淨虧損將減少至 16 億美元。

Now let's turn to our 2024 financial framework on Slide 13, which is mostly in line with what I shared on our Q3 call. We expect net sales for 2024 of approximately $4 billion, which we think will be a low point as we expect to return to growth in 2025. Sales in the first half of the year are expected to be approximately $100 million, reflecting the strong seasonality of respiratory vaccines.

現在讓我們轉向投影片 13 上的 2024 年財務框架，該框架與我在第三季電話會議上分享的內容基本一致。我們預計2024 年的淨銷售額約為40 億美元，我們認為這將是一個低點，因為我們預計將在2025 年恢復成長。上半年的銷售額預計約為1 億美元，反映了強勁的季節性。呼吸道疫苗。

We expect cost of sales of approximately 35% of product sales, in line with our cost of sales framework, which we introduced in our Q3 earnings call last year.

我們預計銷售成本約佔產品銷售額的 35%，這與我們在去年第三季財報電話會議中引入的銷售成本框架一致。

For R&D, we expect full year expenses to be approximately $4.5 billion, down from $4.8 billion in 2023. And for SG&A, we expect full year expenses to be approximately $1.3 billion, down from $1.5 billion in 2023. We also expect taxes to be negligible in 2024.

對於研發，我們預計全年支出約為45 億美元，低於2023 年的48 億美元。對於SG&A，我們預計全年支出約為13 億美元，低於2023 年的15 億美元。我們也預期稅收可以忽略不計2024年。

In our Q3 earnings call, I provided our Moderna operating principles, which largely centered around a very disciplined approach to capital allocation. Our #1 priority has been and will continue to be reinvesting in the business. In addition to the investment into our pipeline, we expect capital expenditures in 2024 to be approximately $0.9 billion as we mostly complete the construction of our facilities across the globe.

在第三季的財報電話會議上，我提供了 Moderna 的營運原則，該原則主要圍繞著非常嚴格的資本配置方法。我們的第一要務一直是並將繼續對業務進行再投資。除了對管道的投資外，我們預計 2024 年的資本支出約為 9 億美元，因為我們已基本完成全球設施的建設。

Our teams are laser-focused on operational improvements for both expense management and working capital. As a result, we expect to end 2024 with approximately $9 billion in cash.

我們的團隊專注於費用管理和營運資本的營運改善。因此，我們預計到 2024 年底將擁有約 90 億美元的現金。

I will now turn the call over to Stephen.

我現在將把電話轉給史蒂芬。

Thank you, Jamey. Good morning or good afternoon, everyone. Today, I'll do a quick review of our clinical highlights from our late-stage programs in 2023 and then look ahead to anticipated milestones in 2024.

謝謝你，傑米。大家早安或下午好。今天，我將快速回顧 2023 年後期計畫的臨床亮點，然後展望 2024 年的預期里程碑。

While we have over 40 programs in development, we will focus on our late-stage pipeline, which consists of 9 programs across 4 franchises, all made significant progress in 2023. Four of these programs are in our respiratory vaccine franchise. We hope to launch all of these potential products by the end of 2025. I'll discuss this further in a moment.

雖然我們有40 多個項目正在開發中，但我們將重點關注我們的後期管道，其中包括4 個特許經營權的9 個項目，所有項目均在2023 年取得了重大進展。其中四個項目屬於我們的呼吸道疫苗特許經營權。我們希望在 2025 年底之前推出所有這些潛在產品。我稍後將進一步討論這個問題。

The other 5 late-stage programs are spread across latent vaccines, oncology therapeutics and rare disease therapeutics. We hope to begin launching these beginning in 2026, and I'll discuss our progress in these areas as well.

另外 5 個後期項目涉及潛在疫苗、腫瘤治療和罕見疾病治療。我們希望從 2026 年開始啟動這些項目，我也將討論我們在這些領域的進展。

In infectious disease vaccines, we've achieved many important clinical milestones in 2023. Within our respiratory vaccine franchise, we filed for RSV vaccine approvals in many countries around the world. We recently presented follow-up data from our Phase III study at the RSVVW meeting that I'll recap in a moment.

在傳染病疫苗方面，我們在 2023 年實現了許多重要的臨床里程碑。在我們的呼吸道疫苗系列中，我們在世界許多國家申請了 RSV 疫苗的批准。我們最近在 RSVVW 會議上展示了 III 期研究的後續數據，我稍後會回顧一下。

In our mRNA-1010 flu program, our Phase III P303 study met its primary safety endpoints and hit all 8 co-primary immunogenicity endpoints against all strains of influenza. We're also excited that we fully enrolled the Phase III immunogenicity and safety study of our next-gen COVID vaccine and the Phase III immunogenicity and safety study of our flu and COVID combination vaccine.

在我們的 mRNA-1010 流感計畫中，我們的 III 期 P303 研究達到了其主要安全終點，並達到了所有流感病毒株的所有 8 個共同主要免疫原性終點。我們也很高興我們全面參與了下一代新冠疫苗的 III 期免疫原性和安全性研究以及流感和新冠疫苗聯合疫苗的 III 期免疫原性和安全性研究。

In our latent and other vaccines franchise, we're proud of the great progress our team made to complete enrollment in the Phase III study of our CMV vaccine in 2023. That study is now accruing cases towards its first interim analysis of efficacy.

在我們的潛伏疫苗和其他疫苗系列中，我們的團隊在2023 年完成CMV 疫苗III 期研究的註冊方面取得了巨大進展，我們對此感到自豪。該研究目前正在積累病例，以期進行首次中期療效分析。

On Slide 17, I want to briefly review the primary analysis for our RSV vaccine, which was first shared in January of 2023. The study met its primary and key secondary endpoints, leading the DSMB to recommend unblinding. Vaccine efficacy was 83.7% against RSV with 2 or more symptoms of lower respiratory tract disease at a median follow-up of 3.7 months with a wide range of 2 weeks to 12 months of total follow-up. The primary analysis showed -- also showed 82.4% and 68.4% vaccine efficacy against 3 or more symptoms and acute respiratory distress, respectively. These data were recently published in the New England Journal of Medicine in December of last year.

在投影片 17 上，我想簡要回顧我們的 RSV 疫苗的主要分析，該分析於 2023 年 1 月首次分享。該研究達到了主要和關鍵的次要終點，導致 DSMB 建議揭盲。中位追蹤時間為 3.7 個月，總追蹤時間為 2 週至 12 個月，疫苗對 2 種或以上下呼吸道疾病症狀的 RSV 的療效為 83.7%。初步分析也顯示，疫苗對 3 種或更多症狀和急性呼吸窘迫的效力分別為 82.4% 和 68.4%。這些數據於去年 12 月發表在《新英格蘭醫學雜誌》。

We've continued to follow the participants in the trial and announced follow-up data at the RSVVW conference earlier this month. An additional analysis showed sustained vaccine efficacy against RSV, with VE of 63.3% against RSV lower respiratory tract disease with 2 or more symptoms through a median follow-up of 8.6 months and a maximum follow-up of 17.7 months. The vaccine efficacy was 74.6% against RSV lower respiratory tract disease associated with shortness of breath, which has been shown to be a key driver of seeking a higher level of medical care and the associated burden costs.

我們繼續追蹤試驗參與者，並在本月稍早的 RSVVW 會議上公佈了後續數據。另一項分析顯示，疫苗對 RSV 的持續療效，在中位追蹤 8.6 個月和最長追蹤 17.7 個月的情況下，針對具有 2 種或更多症狀的 RSV 下呼吸道疾病，VE 為 63.3%。該疫苗針對與呼吸短促相關的 RSV 下呼吸道疾病的功效為 74.6%，已被證明是尋求更高水平的醫療護理和相關負擔成本的關鍵驅動因素。

Now Slide 19 summarizes the overall timing of enrollment, primary efficacy analysis and subsequent analysis overlaid against the epidemiology of RSV over the 2 seasons that have now contributed to the efficacy in the trial. Our trial enrolled steadily over 13 months between November 2021 and December 2022. As a result, the primary efficacy analysis included cases from both the smaller RSV season of 2021 and 2022 and a much more significant RSV season of 2022 and 2023.

現在，投影片 19 總結了入組的總體時間、主要療效分析和隨後的與 RSV 流行病學重疊的分析，這些分析現已對試驗的療效做出了貢獻。我們的試驗在2021 年11 月至2022 年12 月期間的13 個月內穩定入組。因此，主要療效分析包括2021 年和2022 年較小的RSV 季節以及2022 年和2023 年更重要的RSV 季節的病例。

Due to enrollment throughout the year, the median follow-up of the primary analysis was 3.7 months. But as I noted, the maximum follow-up was 12 months. The primary analysis met its success criteria leading the study unblinding.

由於全年入組，初步分析的中位追蹤時間為 3.7 個月。但正如我所指出的，最長追蹤時間為 12 個月。主要分析符合其成功標準，導致研究揭盲。

We continue to preplan additional analysis on April 30, 2023. At that analysis, the median follow-up was 8.6 months, with a maximum follow-up of 17.7 months, or put another way, approximately 17,000 participants were between 9 and 18 months of study follow-up at the time of the analysis, with many completing their second RSV season on the study.

我們繼續預先規劃2023 年4 月30 日的額外分析。在該分析中，中位追蹤時間為8.6 個月，最長追蹤時間為17.7 個月，或者換句話說，大約17,000 名參與者接受了9至18 個月的追蹤。分析時的研究跟進，許多人完成了研究的第二個 RSV 季節。

Per protocol, we are continuing to follow cases through 1 year, but it is evident from the epidemiology, very few cases would be expected in the 6 months after the April 30 cutoff date from the last analysis.

根據協議，我們將繼續追蹤病例長達一年，但從流行病學來看，預計在上次分析 4 月 30 日截止日期後的 6 個月內病例很少。

In summary, we are pleased that the data shows sustained efficacy through 2 seasons, including the large RSV season of 2022-2023. And we look forward to providing further updates from this ongoing study.

總而言之，我們很高興數據顯示了 2 個季節的持續有效性，包括 2022-2023 年大型 RSV 季節。我們期待提供這項正在進行的研究的進一步更新。

We also achieved clinical milestones across our therapeutic franchises in 2023. In oncology, our individualized neoantigen therapy developed in partnership with Merck began Phase III clinical studies in both adjuvant melanoma and non-small cell lung cancer. Both Phase III trials are now actively enrolling.

2023 年，我們的治療系列也實現了臨床里程碑。在腫瘤學方面，我們與默克合作開發的個人化新抗原療法開始了針對輔助黑色素瘤和非小細胞肺癌的 III 期臨床研究。兩項 III 期試驗目前正在積極招募。

Our primary analysis from the Phase II study was recently published in The Lancet, giving greater detail on the 2-year follow-up data that we had released in 2022. Now in December of 2023, we shared top line follow-up data from that same Phase II study in adjuvant melanoma patients confirming the durability of the initially reported responses. At a median follow-up of now 3 years, the recurrence-free survival and distant metastasis-free survival remained extremely favorable, with a reduction of the risk of recurrence or death by 49% and a reduction of the risk of distal metastasis or death of 62%. Both results were highly statistically significant at 3 years.

我們對 II 期研究的主要分析最近發表在《柳葉刀》上，詳細介紹了我們在 2022 年發布的 2 年隨訪數據。現在，在 2023 年 12 月，我們分享了該研究的主要後續數據在輔助黑色素瘤患者中進行的同一II 期研究證實了最初報告的反應的持久性。在目前 3 年的中位追蹤中，無復發生存率和無遠端轉移存活率仍然非常有利，復發或死亡風險降低了 49%，遠端轉移或死亡風險也降低了62%。這兩項結果在 3 年時均具有高度統計顯著性。

And in PA and MMA, our most advanced rare disease therapeutic programs, we continue to see positive clinical data in our Phase I/II studies, including improvements in biomarkers and clinical outcomes such as metabolic decompensations.

在我們最先進的罕見疾病治療計畫 PA 和 MMA 中，我們繼續在 I/II 期研究中看到積極的臨床數據，包括生物標記和代謝失代償等臨床結果的改善。

Now turning to Slide 21 (sic) [Slide 22]. While we're proud of the progress in 2023, we have much more ahead in 2024. Let me take you through some of the late-stage milestones we anticipate for this year. I'll start with our respiratory franchise, where we are targeting the first approval for our RSV vaccine beginning in the first half of 2024, with commercial launches shortly thereafter.

現在轉向投影片 21（原文如此）[投影片 22]。雖然我們對 2023 年的進展感到自豪，但 2024 年我們還有更多的進步。讓我向您介紹我們預計今年將實現的一些後期里程碑。我將從我們的呼吸系統特許經營業務開始，我們的目標是在 2024 年上半年開始首次批准 RSV 疫苗，並在不久後進行商業推出。

With our flu vaccine, we're in discussions with regulators about potential submissions for approvals. And we expect to begin filing this year.

對於我們的流感疫苗，我們正在與監管機構討論潛在的核准申請。我們預計今年開始提交申請。

Phase III data from our next-gen COVID vaccine is expected in the first half of 2024, which will inform the next steps. And we expect Phase III data for our flu and COVID combination vaccine this year.

我們的下一代新冠疫苗的 III 期數據預計將於 2024 年上半年獲得，這將為下一步提供資訊。我們預計今年將獲得流感和新冠聯合疫苗的 III 期數據。

In latent vaccines, we are looking forward to potential efficacy data from our CMV Phase III study.

在潛伏疫苗方面，我們期待 CMV III 期研究的潛在功效數據。

In oncology, we expect continued progress in rolling our 2 Phase III studies in INT for adjuvant melanoma and non-small cell lung cancer. We also expect to expand into additional tumor types this year.

在腫瘤學方面，我們預計針對輔助黑色素瘤和非小細胞肺癌的 INT 兩項 III 期研究將繼續取得進展。我們也預計今年將擴展到其他腫瘤類型。

And finally, in rare diseases, we expect to move into registrational studies for both PA and MMA in 2024. It will be a very busy year, and we look forward to sharing progress with you as the year progresses.

最後，在罕見疾病方面，我們預計在 2024 年進入 PA 和 MMA 的註冊研究。這將是非常忙碌的一年，我們期待著隨著時間的推移與您分享進展。

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

這樣，我會將電話轉給 Stéphane。

Thank you, Stephen and Jamey. For Moderna and the patients we serve, 2024 is all about execution: execution in commercial, execution of our late-stage pipeline and execution with financial discipline.

謝謝你們，史蒂芬和傑米。對於 Moderna 和我們服務的患者來說，2024 年關鍵在於執行：商業執行、後期產品線的執行以及財務紀律的執行。

Starting with commercial. First, our COVID vaccine. We will continue to work with health authorities to increase vaccination rates and improve public health by reducing the substantial burden of disease from COVID in this upcoming 2024-2025 season. While I am pleased with the U.S. market share outcome of the current season, I believe we can and must do better on vaccination rates. Our team are actively working on it already. A few weeks ago, the EU published a new mRNA COVID vaccine tender, up to 36 million doses per year for up to 4 years. Our team is actively working to respond to this tender. We are prioritizing our commercial focus on specific markets around the world to deliver where it matters the most.

從商業開始。首先是我們的新冠疫苗。在即將到來的 2024-2025 年季節，我們將繼續與衛生當局合作，透過減少新冠病毒帶來的巨大疾病負擔，提高疫苗接種率並改善公共衛生。雖然我對本季美國市場份額的結果感到滿意，但我相信我們可以而且必須在疫苗接種率方面做得更好。我們的團隊已經在積極致力於此。幾週前，歐盟發布了新的 mRNA 新冠疫苗招標，每年最多 3,600 萬劑，為期 4 年。我們的團隊正在積極響應本次招標。我們將商業重點放在全球特定市場上，以便在最重要的地方提供服務。

Moving to RSV vaccine candidates. We are very excited about launching the RSV vaccine this year. That will be the launch of our second product our mRNA platform is delivering. The FDA PDUFA date is May 12. If the outcome is positive, we anticipate that ACIP will include mRNA-1345 on the agenda in late June.

轉向 RSV 候選疫苗。我們對今年推出 RSV 疫苗感到非常興奮。這將是我們 mRNA 平台提供的第二款產品的推出。 FDA PDUFA 日期為 5 月 12 日。如果結果積極，我們預計 ACIP 將在 6 月下旬將 mRNA-1345 列入議程。

In Europe, we expect Germany to launch in 2024. We also expect Australia to launch this year, while other markets will likely launch in 2025.

在歐洲，我們預計德國將於 2024 年推出。我們也預期澳洲將於今年推出，而其他市場可能會在 2025 年推出。

In many markets around the world, we need to secure regulatory approval before we can participate in tenders. As communicated last year, given expected approval outside the U.S., Germany and Australia, we anticipate launching early in this market in 2025.

在全球許多市場，我們需要獲得監管部門的批准才能參與投標。正如去年所傳達的那樣，鑑於預期在美國、德國和澳洲以外地區獲得批准，我們預計將於 2025 年儘早在該市場推出。

The RSV market is estimated to be a $10 billion opportunity, consisting roughly of $6 billion to $8 billion in older adults and $2 billion to $4 billion in the pediatric and maternal setting. In 2023, the first year RSV vaccine launches, consumer awareness of RSV and demand for RSV vaccine was strong. The 2023 adult RSV vaccine market was around $2.5 billion. This is quite impressive given it was the first year RSV vaccine were available, they were not even available for a full year, and the products were not approved in many countries. With 2023 RSV vaccination rate as a small percentage of a total addressable market, we are quite excited to launch our product into this large and growing market.

RSV 市場估計有 100 億美元的機會，其中約 60 億至 80 億美元用於老年人，20 億至 40 億美元用於兒科和孕產婦環境。 2023年是RSV疫苗上市的元年，消費者對RSV的認知和對RSV疫苗的需求強勁。 2023年成人RSV疫苗市場規模約25億美元。這是相當令人印象深刻的，因為這是 RSV 疫苗上市的第一年，它們甚至還沒有上市一整年，而且該產品在許多國家都沒有獲得批准。由於 2023 年 RSV 疫苗接種率僅佔整個潛在市場的一小部分，我們非常高興能夠將我們的產品推向這個龐大且不斷增長的市場。

Let me now turn to our RSV vaccine profile. We believe we have the best profile to serve patients and compete in the RSV market, efficacy, safety and ease of use. Our clinical data shows strong vaccine efficacy. We have a well-established safety and tolerability profile that leverages the same mRNA technology that has been delivered in over 1 billion COVID vaccine. Additionally, we have not seen any case of Guillain-Barré Syndrome, or GBS, in our Phase III trial.

現在讓我談談我們的 RSV 疫苗簡介。我們相信，我們擁有最好的形象來服務患者並在 RSV 市場中競爭、功效、安全性和易用性。我們的臨床數據顯示疫苗功效很強。我們擁有完善的安全性和耐受性概況，利用與超過 10 億種新冠疫苗中使用的相同 mRNA 技術。此外，在我們的 III 期試驗中，我們尚未發現任何格林巴利症候群 (GBS) 病例。

We expect to be the only company to offer an RSV vaccine in ready-to-use prefilled syringe, or PFS. Our one-step administration compares well relative to competitive products and require multiple preparation steps by pharmacists and clinicians. As you know, one of our competitors' product requires 9 steps of preparation for each consumer needing a RSV vaccine, and the other competitor's product requires 4 steps of preparation.

我們希望成為唯一一家以即用型預充注射器 (PFS) 形式提供 RSV 疫苗的公司。與競爭產品相比，我們的一步給藥效果很好，並且需要藥劑師和臨床醫生進行多個準備步驟。如您所知，我們的一個競爭對手的產品需要為每位需要 RSV 疫苗的消費者進行 9 個準備步驟，而另一個競爭對手的產品則需要 4 個準備步驟。

With over 90% of the U.S. RSV vaccine given to date in the pharmacy setting, PFS presentation offers ease of use, time savings and the potential to reduce medical errors. Given the labor shortage in retail pharmacy channel, we anticipate our PFS presentation will be welcomed by pharmacists in a very busy respiratory vaccine season, where pharmacists need, in addition to their regular tasks, to administer flu vaccine, COVID vaccine and RSV vaccine.

迄今為止，超過 90% 的美國 RSV 疫苗是在藥房注射的，PFS 演示提供了易用性、節省時間並有可能減少醫療錯誤。鑑於零售藥房管道的勞動力短缺，我們預計我們的 PFS 演示將在非常繁忙的呼吸道疫苗季節受到藥劑師的歡迎，藥劑師除了日常任務外，還需要注射流感疫苗、新冠疫苗和 RSV 疫苗。

Today, we talk about how much progress we made in the late-stage pipeline in 2023. This year, we look forward to continued execution and reporting milestones in each of these programs.

今天，我們談論 2023 年我們在後期管道中取得的進展。今年，我們期待繼續執行並報告每個專案的里程碑。

If you look at this slide, it is going to be a very busy and very exciting year, with multiple Phase III readouts like the COVID next-gen, also flu plus COVID Phase III data and potentially CMV Phase III data. But also, we're going to be filing products like flu, which will be our third product filed, and of course, approval in many countries around the world for RSV.

如果你看一下這張投影片，這將是非常忙碌和非常令人興奮的一年，有多個III 期數據，例如下一代新冠病毒、流感以及新冠病毒III 期數據和潛在的CMV III 期數據。而且，我們也將提交流感等產品的備案，這將是我們備案的第三個產品，當然，RSV 也會在世界許多國家獲得批准。

Finally, we are all committed to exercise financial discipline across the business. While we have resized our manufacturing footprint in 2023, we will continue to find ongoing cost improvements in manufacturing. We will reduce operating expenses in R&D and SG&A and prioritize program in R&D with a near-term commercial potential in areas of unmet medical needs.

最後，我們都致力於在整個企業範圍內遵守財務紀律。雖然我們在 2023 年調整了製造規模，但我們將繼續尋求製造成本的持續改進。我們將減少研發和SG&A方面的營運費用，並優先考慮在未滿足醫療需求領域具有近期商業潛力的研發項目。

Overall, our CapEx will be up mostly -- modestly in 2024 compared to 2023, and we'll mostly complete construction of several important plants in Marlborough, Massachusetts for INT and Canada, U.K. and Australia. In 2025, we expect CapEx to be down significantly.

總體而言，與 2023 年相比，2024 年我們的資本支出將大幅增長，而且我們將基本完成 INT 以及加拿大、英國和澳大利亞位於馬薩諸塞州馬爾伯勒的幾家重要工廠的建設。 2025 年，我們預計資本支出將大幅下降。

We're also targeting working capital improvement. And importantly, as you know, we are adopting AI across the business, which we expect to save time, increase productivity and drive scalability in addition to cost savings. Our use of AI is increasing by the week. And new use cases are exciting to see how our teams are embracing this new tool across the business.

我們也致力於改善營運資本。重要的是，如您所知，我們正在整個業務中採用人工智慧，我們希望除了節省成本之外，還能節省時間、提高生產力並推動可擴展性。我們對人工智慧的使用每週都在增加。新的用例令人興奮地看到我們的團隊如何在整個企業中採用這項新工具。

In summary, 2024 is an important year of execution across our company, one that we set the stage for the next several years. I am very excited by how our company is positioned. I believe 2024 will be a year where many observers of Moderna go from thinking of us as a COVID vaccine company to seeing Moderna as an mRNA platform company with several products approved and more approvals on the way for 2025 and beyond. Over the next few years, our ability to deliver on our mission will increase significantly and be very meaningful for our teams.

總而言之，2024 年是我們公司執行力的重要一年，為我們未來幾年奠定了基礎。我對我們公司的定位感到非常興奮。我相信，2024 年，Moderna 的許多觀察家將把我們視為一家新冠疫苗公司，轉而將Moderna 視為一家mRNA 平台公司，該公司的多種產品已獲得批准，並且在2025 年及以後還會有更多產品獲得批准。在接下來的幾年裡，我們完成使命的能力將顯著增強，這對我們的團隊來說非常有意義。

With that, operator, we'll be now happy to take questions.

接線員，我們現在很樂意回答問題。

(Operator Instructions) Our first question comes from Michael Yee with Jefferies.

（操作員說明）我們的第一個問題來自 Jefferies 的 Michael Yee。

Focusing on RSV. I know you made a number of nice comments about comparing the data. Maybe you could talk to 2 or 3 points. One is perhaps how it will work in the commercial market in the U.S. with contracting. Is that contracting season? Or do you have to have contracts? And how does that work between the 2 different other competitors?

重點關注RSV。我知道您對比較數據提出了很多很好的評論。也許你可以談談2或3點。其中之一可能是它將如何透過合約在美國商業市場運作。那個是簽約季嗎？還是一定要有合約？這兩個不同的競爭對手之間是如何運作的？

And secondly, how would that work at the pharmacy level when either patients or doctors are making the selection given the fact that Pfizer and GSK both had similar sales but different profiles? Maybe talk to those 2 different things and how you expect that to play out for this year.

其次，考慮到輝瑞和葛蘭素史克的銷售額相似但概況不同，當患者或醫生做出選擇時，這在藥房層面如何運作？也許可以談談這兩件不同的事情，以及你預計今年的結果如何。

Great. Thank you, Michael. It's Stéphane. So in terms of contracting, obviously, we cannot start contracting now because our product is not approved. But our medical team has been quite engaged across the board at medical conferences, talking to health care professionals and sharing the great data that was published in December, as you know, from our Phase III in the New England Journal of Medicine. So we have active discussions.

偉大的。謝謝你，麥可。這是史蒂芬。所以在簽約方面，顯然我們現在不能開始簽約，因為我們的產品沒有得到批准。但我們的醫療團隊一直積極參與醫學會議，與醫療保健專業人士交談，並分享 12 月發表的重要數據，如您所知，來自《新英格蘭醫學雜誌》的 III 期研究。所以我們進行了積極的討論。

There is quite high excitement about the possibility, again, if the product was to be approved, to get a prefilled syringe product. As we discussed in my remarks, as you know, labor shortages are a big issue in pharmacy. For any of us that has gone through a pharmacy in the fall, you could see it was very busy, sometime a bit too hectic. And so the leadership of the big retail pharmacies is very engaged to think about COVID versus RSV and how to simplify the workflow, how to reduce medical errors, which is why those medical discussions that we're having so far give me a significant hope that our products will be meaningful tools for our customers.

如果產品獲得批准，獲得預充式註射器產品的可能性再次令人非常興奮。正如我們在發言中所討論的，如您所知，勞動力短缺是藥房的一個大問題。對於我們任何一個在秋天去過藥局的人來說，你都會發現那裡非常繁忙，有時甚至有點太忙碌了。因此，大型零售藥局的領導層非常積極地思考新冠病毒與呼吸道合胞病毒，以及如何簡化工作流程，如何減少醫療錯誤，這就是為什麼我們迄今為止進行的那些醫學討論給了我很大的希望我們的產品對我們的客戶來說將是有意義的工具。

Our next question comes from Gena Wang with Barclays.

我們的下一個問題來自巴克萊銀行的 Gena Wang。

I have 2 very quick questions. First one is regarding the RSV vaccine. What portion of 35,000 to 36,000 participants that completed 2 seasons? And regarding February 29 ACIP meeting, what additional data you will be presenting?

我有兩個非常簡短的問題。第一個是關於 RSV 疫苗。 35,000 至 36,000 名參與者中，有多少人完成了 2 個賽季？關於 2 月 29 日的 ACIP 會議，您將提供哪些額外數據？

And very quickly on 2024 guidance. Now we have a better understanding of both COVID and RSV market size for 2023 and 2024 season. What could be the upside or downside for your 2024 revenue guidance of $4 billion?

並且很快就發布了 2024 年指導。現在，我們對 2023 年和 2024 年季節的新冠病毒 (COVID) 和 RSV 市場規模有了更好的了解。對於 2024 年 40 億美元的收入指引來說，上行或下行可能是什麼？

Great. Thanks, Gena. I'll take the first part of that. So I actually can't -- I don't know, off the top of my head, the proportion because they're both in Southern and Northern Hemisphere participants that were enrolled in the study. And so counting the 2 RSV seasons will depend upon that.

偉大的。謝謝，吉娜。我將採取第一部分。所以我其實不能——我不知道這個比例，因為他們都是南半球和北半球的參與者，都參加了這項研究。因此，計算 2 個 RSV 季節將取決於此。

It is a sizable proportion because as I said, the maximum follow-up at the additional analysis is about 18 months. Median was 9 months. And so by definition, about half, as you just said, about 17,000 participants were between it. And we did enroll pretty continuously over 13 months, not exactly evenly, but pretty close to it. So I don't want to give you an inaccurate number, but I would suspect it is a pretty sizable proportion because of that steady, pretty consistent enrollment over the course of 13 months. It's not exactly equal, but it trended that direction.

這是一個相當大的比例，因為正如我所說，額外分析的最長追蹤時間約為 18 個月。中位數為 9 個月。因此，根據定義，正如您剛才所說，大約有一半的參與者介於兩者之間。我們確實在 13 個月內連續註冊，雖然不完全均勻，但非常接近。所以我不想給你一個不準確的數字，但我懷疑這是一個相當大的比例，因為在 13 個月的過程中，註冊人數穩定、相當一致。雖然並不完全相等，但趨勢是這個方向。

As far as additional data for the ACIP meeting, we'll obviously continue to provide updates from any additional analysis we're doing on durability. We obviously have immunogenicity data as well as data across different subpopulations. And if we're fortunate enough to have the opportunity to present at the ACIP, we will, of course, listen to the committee on anything they would like to see as well on the performance of mRNA-1345 as a vaccine and the performance of the vaccines in general in terms of durability as it guides decision-making around repeat dosing or boosting on some schedule in the public health.

至於 ACIP 會議的其他數據，我們顯然會繼續提供我們正在進行的關於耐用性的任何其他分析的更新。顯然我們有免疫原性數據以及不同亞群的數據。如果我們夠幸運有機會在 ACIP 上發言，我們當然會聽取委員會關於他們希望看到的任何內容以及 mRNA-1345 作為疫苗的性能和疫苗性能的意見。疫苗總體上在耐久性方面具有指導意義，因為它可以指導公共衛生領域重複給藥或按計劃加強疫苗接種的決策。

Thanks, Stephen. And Gena, it's Stéphane. On the upside and downside on the sales for this year, I think on the upside, obviously, the COVID in Europe, as I just mentioned, we couldn't participate in the market last fall. The new tender is an opportunity for us to participate. Quite a number of doctors, hospitals, public health leaders have actually complained that the Moderna vaccine, given the higher efficacy reported for reduction of hospitalization, was not available, especially for the elderly, for immunocompromised people. So that's an interesting upside.

謝謝，史蒂芬。吉娜，是史蒂芬。關於今年銷售的上行和下行，我認為從上行來看，顯然，正如我剛才提到的，歐洲的新冠疫情，我們去年秋天無法參與市場。新的招標是我們參與的一個機會。事實上，相當多的醫生、醫院、公共衛生領導者抱怨說，鑑於Moderna疫苗在減少住院方面的功效較高，但他們卻無法使用，特別是對於老年人和免疫功能低下的人。所以這是一個有趣的好處。

Of course, the vaccination rate in the U.S. as we reported, the vaccination rate in the current ending season was lower than last year. As I said in my remarks, we need to do better to protect more people. And our team is actively already working in a cross-functional matter to address the VCR and increase the vaccination rates. And the other upside could be the RSV both the market growth as well as our share, how quickly can we get share from the current 2 solutions available.

當然，正如我們所報導的，美國的疫苗接種率，目前末季的疫苗接種率低於去年。正如我在演講中所說，我們需要做得更好，保護更多的人。我們的團隊已經在積極進行跨職能事務，以解決 VCR 問題並提高疫苗接種率。另一個好處可能是市場成長和我們的份額的 RSV，我們能多快地從目前的 2 個可用解決方案中獲得份額。

On the downside, of course, the vaccination rate could be a downside. And the other one is, of course, timing of RSV launch, given we rely on regulators for the approval of products and then the public health recommendations like CDC or the different ITAGs in the different countries that could, of course, delay launches and, of course, impacting sales.

當然，不利的一面是疫苗接種率可能是個不利因素。當然，另一個問題是 RSV 發布的時間，因為我們依賴監管機構批准產品，然後依賴 CDC 或不同國家的不同 ITAG 等公共衛生建議，當然，這些建議可能會延遲發布，當然，影響銷售。

Our next question comes from Ellie Merle with UBS.

我們的下一個問題來自瑞銀集團的埃莉梅爾。

Just turning to the CMV Phase III, can you talk a little bit about what you would view as clinically meaningful or commercially relevant on vaccine efficacy? And if successful, also how are you thinking about use in seronegative versus seropositive patients?

就 CMV III 期而言，您能否談談您認為疫苗功效的臨床意義或商業相關性？如果成功的話，您如何考慮在血清陰性患者和血清陽性患者中使用？

For sure. So thank you for the question. So in CMV, obviously, there's currently no vaccine that can prevent an infection against CMV and as it is a source of devastating birth defects, anything that provides a statistically significant reduction in the rate of infection and, therefore, vertical transmission would be, we think, terrific. Now the minimum bar that we are powering in our study with support is a vaccine efficacy of approximately 50%. As we've shared previously, anything above that would obviously beat our expectations and be incredibly exciting for the field.

一定。謝謝你的提問。因此，對於鉅細胞病毒，顯然，目前沒有疫苗可以預防鉅細胞病毒感染，而且由於鉅細胞病毒是毀滅性出生缺陷的一個來源，因此任何能夠在統計學上顯著降低感染率的方法，因此，垂直傳播都將是，我們想想，棒極了。現在，我們在研究中支持的最低標準是疫苗效力約為 50%。正如我們之前所分享的，任何高於這個數字的結果顯然都會超出我們的預期，並且對該領域來說是令人難以置信的令人興奮。

We are in the Phase III study, enrolling both seropositive and seronegative participants. And part of the reason for that is that there's currently no broadly used diagnostic. And so we want to demonstrate benefit or safety in both populations because we do believe that the most likely use of the vaccine could be that it's given regardless of sero status to both seronegatives and seropositives. And there are potential benefits for seropositives that could include control of shedding or viremia or other long-term sequela of CMV, but we would have to prove those. And again, those are not something we're exploring explicitly in the current Phase III study.

我們正在進行第三階段研究，招募血清陽性和血清陰性參與者。部分原因是目前還沒有廣泛使用的診斷方法。因此，我們希望證明對這兩個人群的益處或安全性，因為我們確實相信，最有可能使用該疫苗的可能是，無論血清陰性和血清陽性的血清狀態如何，都可以接種該疫苗。血清陽性有潛在的好處，可能包括控制鉅細胞病毒脫落或病毒血症或其他長期後遺症，但我們必須證明這些。再說一遍，這些並不是我們在目前第三階段的研究中明確探索的內容。

So as a practical matter, from a labeling perspective and a launch perspective, our goal is to try and launch the product for both seropositives and seronegatives so that no diagnostic will be needed and it can be broadly used across populations to try and prevent the devastating effects of CMV on vertical transmission to newborn babies.

因此，作為一個實際問題，從標籤的角度和推出的角度來看，我們的目標是嘗試推出針對血清陽性和血清陰性的產品，這樣就不需要診斷，並且可以在人群中廣泛使用，以嘗試預防毀滅性的災難。CMV 對新生兒垂直傳播的影響。

Our next question comes from Hartaj Singh with Oppenheimer.

我們的下一個問題來自哈塔吉·辛格和奧本海默。

You indicated that you're going to complete enrollment for CMV this year and maybe have a readout. Can you just walk us through the steps of how that would look like and maybe just give us some ideas on powering statistical assumptions?

您表示今年將完成 CMV 註冊，並且可能會進行讀數。您能否向我們介紹一下具體的步驟，並為我們提供一些支持統計假設的想法？

Yes, of course. Thanks, Hartaj. So we're currently fully enrolled, and we're accruing cases in that study. And I think as we've shared before, we've actually made substantial progress in a number of cases.

是的當然。謝謝，哈塔傑。因此，我們目前已全部註冊，我們正在該研究中累積案例。我認為正如我們之前所分享的，我們實際上在許多案例中取得了實質進展。

It is a case-driven endpoint, and we'll need to see approximately 80 cases before we'll do the first interim analysis for efficacy. That -- 81 cases, to be specific. That interim analysis for efficacy will look a lot like our other vaccine efficacy studies. DSMB will evaluate that data. And if we meet the statistical threshold, which is for early efficacy, meaning we're doing better than our minimum of 49.5% vaccine efficacy, then they will, at that moment, tell us to unblind and share the results. And of course, we will share them broadly with the world.

這是一個病例驅動的終點，在進行第一次中期療效分析之前，我們需要查看大約 80 個病例。具體來說，是 81 起案件。功效的中期分析看起來很像我們的其他疫苗功效研究。 DSMB 將評估該數據。如果我們達到了統計閾值，即早期療效，這意味著我們做得比我們的最低 49.5% 疫苗功效要好，那麼他們會在那時告訴我們取消盲法並分享結果。當然，我們將與世界廣泛分享它們。

If, for whatever reason, we don't quite have the statistical power in that first interim analysis of efficacy, the study is powered to continue on and continue to recruit cases towards a final analysis of efficacy. Now given the rate of -- the final analysis at 112 cases.

如果出於某種原因，我們在第一次中期療效分析中不具備足夠的統計能力，則該研究有能力繼續進行並繼續招募病例以進行最終療效分析。現在給出的比率－最終分析為112例。

Now given the rate of a case accrual that we're currently seeing in the study, we do expect that we will have more than enough cases this year. We are, therefore, pretty confident that we are going to be seeing a readout from the interim analysis, possibly even the final analysis for efficacy in 2024. But again, since it's case- and event-driven, we just have to bide our time. And ultimately, we will depend upon the DSMB to tell us whether or not we've met that statistical threshold.

現在，考慮到我們目前在研究中看到的病例應計率，我們確實預計今年的病例將綽綽有餘。因此，我們非常有信心，我們將看到中期分析的結果，甚至可能在 2024 年看到最終的療效分析。但同樣，由於它是案例和事件驅動的，我們只能等待時機。最終，我們將依靠 DSMB 來告訴我們是否達到了該統計閾值。

Our next question comes from Luca Issi with RBC Capital.

我們的下一個問題來自 RBC Capital 的 Luca Issi。

Maybe, Stephen, on INT, maybe can you remind us what's your latest thinking in terms of potential for accelerated approval there for melanoma?

史蒂芬，在 INT 上，您能否提醒我們您對黑色素瘤加速批准潛力的最新想法是什麼？

And then maybe on the additional tumor types that you guys and Merck are thinking about it, can you just maybe talk about what are tumor types that you're contemplating and whether those tumor types are going to be in the adjuvant settings or in the metastatic settings?

And then maybe on the additional tumor types that you guys and Merck are thinking about it, can you just maybe talk about what are tumor types that you're contemplating and whether those tumor types are going to be in the adjuvant settings or in the metastatic設定?

And then maybe on RSV quickly, can you just maybe expand on durability in the context of your competitor? Is there a scenario where ACIP recommends the GSK vaccine for every other year versus your vaccine for every year? Any color there, much appreciated.

然後也許很快就可以在 RSV 上，您能否在競爭對手的背景下擴展耐用性？是否存在 ACIP 建議每隔一年接種葛蘭素史克疫苗而不是每年接種您的疫苗的情況？任何顏色都有，非常感謝。

Quite a few questions there. I'll try and get them all. I apologize if I forget any one. So first, on the question of INT and accelerated approval in the adjuvant melanoma setting. So as we've said before, we continue to be really excited about the data and are excited to start looking to talk to regulators about it.

那裡有不少問題。我會盡力把它們全部拿到。如果我忘記了任何一個，我深表歉意。首先，關於 INT 和加速批准黑色素瘤輔助治療的問題。因此，正如我們之前所說，我們仍然對這些數據感到非常興奮，並很高興開始與監管機構討論此事。

There have been 3 things that we've tried to say that had to be true for us to believe it was appropriate to even ask about accelerated approval. The first was we had to see durability. And clearly, the data that we just saw from December just 2 months ago shows that durability and really a clear statistically significant result where the comparator arm, the control arm, looks really just like the labeled data. And so we're incredibly encouraged by that durability. That was criteria one.

我們試圖說明三件事，這些事情必須是真實的，我們才能相信詢問加速批准是適當的。首先是我們必須看到耐用性。顯然，我們剛剛在 2 個月前看到的 12 月數據顯示了耐用性，並且確實是一個明顯的統計顯著結果，其中比較器臂、控制臂看起來確實與標記數據一樣。因此，我們對這種耐用性感到非常鼓舞。這是標準一。

But the second and third are still there and really important. The second is that we have to substantially enroll the confirmatory Phase III study. For an accelerated approval in this space, we do believe we have to show we've really already done the diligence to allow that confirmatory data to come in so that 3 or 4 years from now, that further readout would confirm anything that would happen in accelerated approval context.

但第二個和第三個仍然存在並且非常重要。第二是我們必須大量招募驗證性三期研究。為了加速這一領域的批准，我們確實相信我們必須證明我們確實已經盡了努力，允許確認性數據進入，以便從現在起 3 或 4 年後，進一步的讀數將確認將發生的任何事情加速審批環境。

And then the third and perhaps now increasingly important criteria was that we had to establish the commercial manufacturing facility. So as we've announced, we've been building a facility in Marlborough, Massachusetts. It will be a purpose-built, personalized, individualized neoantigen therapy facility that is ultimately what will be licensed to create this product for the world, whether it's in an accelerated context or in the future with full approval. That facility is coming online. We look forward to hosting many of you and others in tours as we bring it online. But without that facility, there isn't really a product here to talk about.

然後第三個也許現在變得越來越重要的標準是我們必須建立商業製造設施。正如我們所宣布的，我們一直在馬薩諸塞州馬爾伯勒建造一座工廠。它將是一個專門建造的、個性化的、個人化的新抗原治療設施，最終將被許可為全世界生產該產品，無論是在加速的情況下還是在未來獲得充分批准。該設施即將上線。當我們將其在線化時，我們期待接待您和其他人的參觀。但如果沒有這個設施，這裡就沒有真正的產品可以談。

And so all 3 of them are essential. We're making progress on all 3. And I think the most exciting thing is what you were just alluding to, which is the durability of the benefit we've been seeing really causes us to now lean into completing -- working hard to complete the enrollment of that confirmatory study criteria 2 and finish the build-out of that Marlborough facility, which is the third criteria.

因此，這三者都是必不可少的。我們在所有這三個方面都取得了進展。我認為最令人興奮的事情就是你剛才提到的，我們所看到的好處的持久性確實使我們現在傾向於完成——努力完成驗證性研究標準2 的註冊並完成馬爾堡設施的擴建，這是第三個標準。

Now on the point of other indications that we're going after, the -- we will -- I will defer to our partners, Merck, on the specifics. We will do it together at the right time, opening up additional Phase III and confirmatory studies. We do expect to open multiple this year. Those include some additional adjuvant indications. They also include some potential metastatic indications, and we are looking at monotherapy indications. And they can be either in places where PD-1s, KEYTRUDA may not be indicated or even earlier lines of therapy. And so all of those are under consideration. And as soon as we start those studies up and begin enrolling, of course, we'll make announcements about them with our partner, Merck.

現在，關於我們正在尋求的其他跡象，我們將在具體細節上聽取我們的伴侶默克的意見。我們將在適當的時候共同進行這項工作，進行更多的 III 期研究和驗證性研究。我們預計今年將開設多家。這些包括一些額外的輔助適應症。它們也包括一些潛在的轉移適應症，我們正在研究單一療法適應症。它們可以用於 PD-1、KEYTRUDA 可能不適用的地方，甚至可以用於早期治療。所以所有這些都在考慮之中。當然，一旦我們開始這些研究並開始招募，我們就會與我們的合作夥伴默克公司一起發布相關公告。

Now lastly, on the question of RSV, we continue to be really enthusiastic about the data of our -- that our product has. And I think the durability now shown through these -- through the second large season is quite encouraging. We'll be sharing that data with the ACIP. Well, first, we have to get through the regulatory process and approval in this country, and Stéphane mentioned our PDUFA date in May. And if we have the opportunity, we'll be sharing the data with the ACIP, which includes, in our case, booster data on immunogenicity from ongoing work that has actually already previously been presented publicly at meetings.

最後，關於 RSV 問題，我們仍然對我們產品的數據充滿熱情。我認為現在透過這些——透過第二個大賽季——所表現出的耐久性是相當令人鼓舞的。我們將與 ACIP 共享這些數據。嗯，首先，我們必須通過這個國家的監管程序和批准，Stéphane 在 5 月提到了我們的 PDUFA 日期。如果有機會，我們將與 ACIP 共享數據，在我們的案例中，其中包括正在進行的工作中的免疫原性增強數據，這些數據實際上之前已經在會議上公開提出過。

And so just like our competitors, we have shared data of what a second dose looks like in terms of boosting, neutralizing antibody titers back up, both at 1 year, and we're also going to be looking at 2 years. And those -- all of the data ourselves, as well as that booster -- similar booster data from the competitor products, will likely be brought together to inform the ACIP's recommendation of how they think RSV vaccines should be readministered when a booster might be necessary. It really falls to the committee to make that determination, not us.

因此，就像我們的競爭對手一樣，我們分享了第二劑疫苗在增強、中和抗體滴度方面的數據，都是在 1 年時進行的，我們也將在 2 年時進行研究。這些——我們自己的所有數據，以及加強劑——來自競爭對手產品的類似加強劑數據，可能會被匯總起來，以告知ACIP 的建議，即他們認為在可能需要加強劑時應如何重新接種RSV疫苗。做出這項決定的其實是委員會，而不是我們。

Your question was about whether we expect there to be any difference or distinction in terms of how they treat the vaccine. At this point, given the immunogenicity data and booster data that has been shared across all 3 products, which is remarkably consistent, as well as the consistent picture in terms of efficacy, including some leading efficacy for all products in the second year, we would suspect that they will continue to view the products as more similar than not and, therefore, continue with consistent recommendations. But it's really up to the committee to make that determination. At least from my perspective, I certainly think the science would support that.

你的問題是關於我們是否期望他們對待疫苗的方式有任何差異或差異。此時，考慮到所有 3 個產品共享的免疫原性數據和加強數據非常一致，並且功效方面也一致，包括第二年所有產品的一些領先功效，我們將懷疑他們會繼續認為產品相似，因此會繼續提供一致的推薦。但這其實是由委員會做出決定的。至少從我的角度來看，我當然認為科學會支持這一點。

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。

This is Elizabeth on for Salveen. Two questions from us. First, can you just remind us of where you stand with evaluating the RSV vaccine in the pediatric population?

這是薩爾文的伊麗莎白。我們提出兩個問題。首先，您能否提醒我們您在評估兒科族群 RSV 疫苗方面的立場？

And then for the Phase III CMV vaccine, can you walk us through what you've seen on durability to date and how you're thinking about the durability of that vaccine, particularly as it relates to the potential commercial opportunity in a younger adult women/adolescent population?

然後，對於 III 期 CMV 疫苗，您能否向我們介紹一下您迄今為止所看到的持久性以及您如何看待該疫苗的持久性，特別是因為它與年輕成年女性的潛在商業機會有關/青少年人口？

Yes. So I'll take the question. So on RSV pediatrics, we have not started the study yet. We are, of course, considering taking this into a Phase III. It is in the clinic with Phase I/II. We are waiting for the data to be able to move at the right time into the pediatric setting.

是的。那我來回答這個問題。所以關於RSV兒科，我們還沒有開始研究。當然，我們正在考慮將其納入第三階段。目前處於 I/II 期臨床階段。我們正在等待數據能夠在正確的時間轉移到兒科環境。

In terms of CMV, we don't have data yet on durability. Again, like we've done for other programs, when we share the data, we share the data, including durability because it's very important. As you know, the benefits of young women is they have a very strong immune system. As we've shown in our INT programs, our T cells work very well in terms of the vaccination technology of Moderna. So we really expect to have good durability over time. But again, we have to wait for the data to make such a determination.

就 CMV 而言，我們還沒有耐久性資料。同樣，就像我們對其他程式所做的那樣，當我們共享數據時，我們共享數據，包括持久性，因為它非常重要。如您所知，年輕女性的好處是她們擁有非常強大的免疫系統。正如我們在 INT 計畫中所展示的那樣，我們的 T 細胞在 Moderna 的疫苗接種技術方面效果非常好。因此，我們確實希望隨著時間的推移具有良好的耐用性。但同樣，我們必須等待數據才能做出這樣的決定。

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

我們的下一個問題來自美國銀行的傑夫·米查姆。

This is Alex Hammond on for Geoff Meacham. So a great way to equalize vaccine efficacy results is to use a correlative of protection. So for RSV, when do you think we could have a line of sight into this type of metric? And how important could this be for our competitive dynamics?

我是亞歷克斯·哈蒙德 (Alex Hammond)，替補傑夫·米查姆 (Geoff Meacham)。因此，均衡疫苗功效結果的一個好方法是使用保護相關性。那麼對於 RSV，您認為我們什麼時候可以了解這類指標？這對於我們的競爭動力有多重要？

It's Stéphane, so...

這是史蒂芬，所以...

Sorry -- small technical stuff. So I'm back. I believe I caught the end of the question, which is how -- when do we think we'll have a correlate of protection that can inform dynamics, both between products and boosting, if that's correct.

抱歉——一些小技術問題。所以我回來了。我相信我抓住了問題的結尾，即我們何時認為我們會擁有一種保護相關性，可以為產品和增強之間的動態提供資訊（如果這是正確的）。

The -- we and all the other manufacturers have been sharing publicly their -- our work on a correlate of protection. We do believe that we've identified a strong candidate in neutralizing antibodies, not surprisingly, from our clinical study. We've been sharing that data with regulators, and we've been sharing the preliminary analysis with public health officials, including advisory groups and ITAGs like the ACIP.

我們和所有其他製造商一直在公開分享他們在保護相關方面的工作。我們確實相信，我們已經從我們的臨床研究中發現了一種強大的中和抗體候選藥物，這並不奇怪。我們一直在與監管機構分享這些數據，並與公共衛生官員（包括諮詢小組和 ACIP 等 ITAG）分享初步分析。

We will be publishing that data and ultimately submitting that to our regulatory submissions as a correlate through this -- the balance of this year. And if we, and I think the other competitors are successful in establishing neutralizing antibodies against RSV as a correlate of protection in RSV, then it really will probably be the primary way that public health officials make determinations about revaccination and boosting and, ultimately, how we maintain durable protection against RSV for high-risk populations like older adults.

我們將發布這些數據，並最終將其提交給我們的監管提交文件，作為今年剩餘時間的相關數據。如果我們，以及我認為其他競爭對手成功建立了針對 RSV 的中和抗體，作為 RSV 保護的相關性，那麼這確實可能是公共衛生官員決定重新接種疫苗和加強疫苗接種以及最終如何決定的主要方式。我們為老年人等高危險群提供對RSV 的持久保護。

From a competitive dynamic perspective, once each product has established their correlate, their correlate will relate to them. But we do think there's probably going to be more commonality than not in the correlates of protection, which makes sense because at the end of the day, we're still talking about the same virus and vaccination against it for all 3 products.

從競爭動態的角度來看，一旦每個產品建立了它們的關聯性，它們的關聯性就會與它們相關。但我們確實認為，在保護相關性方面可能會存在更多的共通性，這是有道理的，因為歸根結底，我們仍然在談論同一種病毒以及針對所有 3 種產品的疫苗接種。

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特倫斯·弗林。

I was just wondering if you could provide an update on your discussions with FDA for 1010, your seasonal flu vaccine? And what's gating to filing here?

我只是想知道您能否提供與 FDA 討論季節性流感疫苗 1010 的最新情況？在這裡提交申請的門檻是什麼？

Thanks. So we are speaking to the FDA and regulators around the world about what would be -- what they would like to see from a submission perspective for our first-generation of our influenza program, our mRNA-1010 programs as you referenced.

謝謝。因此，我們正在與 FDA 和世界各地的監管機構討論他們希望從提交的角度看到我們的第一代流感項目，即您提到的 mRNA-1010 項目。

I don't have any specific updates right now. We're in those conversations as we speak. I really don't want to get ahead of them. The kinds of things we're talking about are, what's the total submission data package? What's the duration of follow-up in some of these studies? And what additional studies or data might be supportive to the application? Those conversations are ongoing. We will provide updates as and when we have them, but I have nothing further to add right now.

我現在沒有任何具體更新。當我們說話時，我們正處於這些對話中。我真的不想領先他們。我們討論的問題是，提交的資料包總量是多少？其中一些研究的追蹤持續時間是多久？哪些額外的研究或數據可能支持該申請？這些對話正在進行中。我們將在有更新時提供更新，但我現在沒有什麼可補充的。

Our next question comes from Jessica Fye with JPMorgan.

我們的下一個問題來自摩根大通的傑西卡·菲伊。

For INT, can you talk about what's driving your confidence to go into metastatic settings? How's enrollment going in the Phase III melanoma trial? And I know you touched on manufacturing being important here. What's the status of that manufacturing scale-up work? And when is that facility going to be ready to go live?

對於 INT，您能談談是什麼讓您有信心進入轉移性環境嗎？ III 期黑色素瘤試驗的招募進度如何？我知道你談到了製造業在這裡的重要性。擴大生產規模的工作進度如何？該設施什麼時候準備投入使用？

Great questions all. So I'll take the first part of that. So first on metastatic. So we have not formally decided or announced that we're going into a metastatic indication. We do have data from our Phase I study -- our initial Phase I study in metastatic patients, including non-small cell lung cancer. But we have not yet made a determination that we're going into the metastatic indication.

所有的問題都很好。所以我將討論第一部分。首先是轉移性。因此，我們尚未正式決定或宣布我們將進入轉移適應症。我們確實有第一階段研究的數據——我們針對轉移性患者（包括非小細胞肺癌）的初步第一階段研究。但我們還沒決定是否要進入轉移適應症。

And I think behind your question is a view that I would agree with, which is to the extent that INT is going to provide a really substantial benefit, we think it is probably in earlier lines of therapy. So not just adjuvant but perhaps even Stage 1 disease or a Stage 2 disease, depending on the indication because the safety and tolerability profile is, we think, incredibly favorable and the benefits we're seeing are pretty remarkable from an immune perspective.

我認為你的問題背後有一個我同意的觀點，即 INT 將提供真正實質的益處，我們認為這可能是在早期的治療中。因此，不僅是佐劑，甚至可能是1 期疾病或2 期疾病，這取決於適應症，因為我們認為安全性和耐受性非常有利，而且從免疫角度來看，我們看到的好處非常顯著。

That said, there is still a really high unmet need in the metastatic space, and even immunotherapies like the PD-1s, like KEYTRUDA provide a substantial benefit there. And so at the right time, we may, well, choose to study the metastatic indication, but as I said -- or metastatic indications and settings. But as I said, we have not yet formally decided to do that today. And we're really focused on adjuvant and earlier and monotherapy principally.

也就是說，轉移領域仍然存在很高的未滿足需求，甚至像 PD-1 和 KEYTRUDA 這樣的免疫療法也能在那裡提供實質的好處。因此，在正確的時間，我們可能會選擇研究轉移適應症，但正如我所說，或轉移適應症和背景。但正如我所說，我們今天尚未正式決定這樣做。我們確實主要關注輔助療法、早期療法和單一療法。

On the question on the manufacturing process, we're in enrollment. We have substantially scaled up our ability to enroll patients in those Phase III studies. I can assure you that with our partner, Merck, we wouldn't have opened a second Phase III study and be talking about the third if we didn't have confidence in our ability to rapidly meet the demand for -- the substantial demand from those clinical research sites for INT manufacturing.

關於製造過程的問題，我們正在招生。我們已經大幅提高了招募患者參加這些 III 期研究的能力。我可以向您保證，如果我們對快速滿足需求的能力沒有信心，我們就不會與我們的合作夥伴默克一起開展第二項 III 期研究，也不會談論第三項研究。那些用於INT製造的臨床研究場所。

We haven't specifically put out numbers, but suffice to say, we are rapidly enrolling in those studies, and we would expect to make substantial progress this year and even perhaps getting close to completing enrollment in at least one of those studies if it continues the trajectory.

我們還沒有具體公佈具體數字，但足以說明的是，我們正在迅速招募這些研究，我們預計今年將取得實質進展，如果繼續下去，甚至可能接近完成至少一項研究的招募軌跡。

So we're excited about the progress we've made in scaling up the manufacturing for clinical supply. We're excited about the progress we're making right now in enrolling patients in the demand that we're seeing from clinical sites. And we do believe that we've solved a lot of the -- for clinical research, for clinical development, the manufacturing requirements.

因此，我們對擴大臨床供應生產規模所取得的進展感到興奮。我們對目前在根據臨床站點的需求招募患者方面所取得的進展感到興奮。我們確實相信我們已經解決了許多臨床研究、臨床開發和製造要求。

The question then becomes commercial. And as we alluded to a few minutes ago, the Marlborough site would really become the purpose-built commercial site, which means to not only be able to deliver high-quality products at high volumes but also do it at a valuable price and cost point.

那麼這個問題就變成商業問題了。正如我們幾分鐘前提到的，馬爾堡網站將真正成為專門建造的商業網站，這意味著不僅能夠大量提供高品質的產品，而且還能以有價值的價格和成本點做到這一點。

And all of that work is ongoing. We've made great progress in building that site. Our goal is to establish that site for at least clinical supply this year. But we haven't provided further guidance on when we will have that fully operational for potential commercial use. And ultimately, it depends upon discussions with regulators as well.

所有這些工作正在進行中。我們在建立該網站方面取得了很大進展。我們的目標是在今年建立該站點至少用於臨床供應。但我們尚未就何時將其全面投入潛在商業用途提供進一步的指導。最終，這也取決於與監管機構的討論。

Kevin, we'll take our last question.

凱文，我們來回答最後一個問題。

Okay. Our last question comes from Evan Wang with Guggenheim Securities.

好的。我們的最後一個問題來自古根漢證券公司的 Evan Wang。

Two from me. First on RSV. I know there are some additional studies to expand the initial population. Can you comment on when we may see data from the Phase IIIs in 50-plus and the high-risk younger adults and when you could potentially supplement a filing if everything is positive?

我的兩個。首先是RSV。我知道還有一些額外的研究來擴大初始人群。您能否評論一下我們什麼時候可以看到 50 歲以上和高風險年輕人的 III 期數據？如果一切都是積極的，您什麼時候可以補充備案？

And then I know you commented on Australia. So just as you were thinking about -- or as you've talked about Australia as a proxy for COVID sales in 2023. Now can you comment on how [integral] Australia will be for your RSV launch and as we look for trends in COVID vaccination rates?

然後我知道你評論了澳洲。正如您所想的那樣，或者正如您所談論的那樣，澳洲將成為2023 年新冠病毒銷售的代表。現在，您能否評論一下澳洲將如何為您的RSV 發布以及我們尋找新冠病毒的趨勢提供幫助？疫苗接種率？

Great. I'll quickly take the first part of that and then hand it over to Stéphane for the second.

偉大的。我將快速完成第一部分，然後將第二部分交給 Stéphane。

So the additional data on 50-plus we have, obviously, immunobridging data and coadministration data, we'll be sharing that at the appropriate time with public health officials and others. It could be as soon as the ACIP. It just depends on when the data comes in, as well as the 18-plus high-risk populations.

因此，顯然，我們擁有 50 多個患者的額外數據，包括免疫橋接數據和共同給藥數據，我們將在適當的時候與公共衛生官員和其他人分享這些數據。最早可能會在 ACIP 召開時舉行。這僅取決於數據何時到來，以及 18 歲以上的高風險族群。

In your question about getting this in the label, it's important to note that public health officials can recommend use even beyond the label and may choose to do that, but our responsibility will be to get it in the label. And we will need to complete the initial BLA before then we could submit the sBLA to get that data in the label. And so obviously, it would follow shortly after our hopefully successful PDUFA outcome in May.

在您關於將其添加到標籤中的問題中，重要的是要注意公共衛生官員可以建議甚至在標籤之外使用，並且可能選擇這樣做，但我們的責任是將其添加到標籤中。我們需要先完成初始 BLA，然後才能提交 sBLA 以取得標籤中的資料。顯然，它會在 5 月我們希望獲得成功的 PDUFA 結果之後不久進行。

Thanks, Stephen. And on Australia, so a few things. First, I mean our team has delivered a strong performance on COVID in Australia. We've been helping the government since the beginning of the pandemic. As you recall, we have announced a long-term 10-year partnership with the Australian government, and we are currently building a plant in Melbourne that is advancing quite successfully. And we are in active discussions with regulators around Australia for RSV approval.

謝謝，史蒂芬。關於澳大利亞，有幾件事。首先，我的意思是我們的團隊在澳洲應對新冠疫情方面表現出色。自大流行開始以來，我們一直在幫助政府。大家還記得，我們​​已經宣布與澳洲政府建立為期10年的長期合作關係，目前我們正在墨爾本建造一家工廠，進展相當順利。我們正在與澳洲各地的監管機構積極討論 RSV 的批准。

The point I will make is that Australia, as you know, is a quite different market commercially to the U.S. It's really mostly driven by the government. So I will compare Australia more to a European market than to the U.S. market. I don't think we can draw any positive or negative correlation, and so what happened in Australia, COVID, it's what will happen in the U.S. in the full '24 with '25.

我要指出的一點是，正如您所知，澳洲是一個與美國完全不同的商業市場。它實際上主要是由政府驅動的。因此，我更多地將澳洲與歐洲市場進行比較，而不是與美國市場進行比較。我不認為我們可以得出任何正相關或負相關，所以在澳洲發生的事情，新冠病毒，這就是美國在整個 24 世紀到 25 年間將發生的事情。

Thank you so much for the questions today. Thank you for taking the time to be with us. We look forward to talking and seeing many of you in the coming days and weeks. I hope that you will have on March 27, the Annual Vaccine Day in your calendar. We will start the presentation at 9:00 a.m. Eastern time. So have a great day, and thank you for joining.

非常感謝您今天提出的問題。感謝您抽出時間與我們同在。我們期待在接下來的幾天和幾週內與你們中的許多人交談和見面。我希望您將 3 月 27 日這一年度疫苗日列入您的日曆中。我們將於東部時間上午 9:00 開始演示。祝您有美好的一天，感謝您的加入。

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。