莫德納 (MRNA) 2025 Q2 法說會逐字稿

Good day, and thank you for standing by. Welcome to Moderna's second quarter 2025 conference call. (Operator Instructions) Please be advised today's conference is being recorded.

您好，感謝您的支持。歡迎參加 Moderna 2025 年第二季電話會議。（操作員指示）請注意，今天的會議正在錄音。

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

現在，我想將會議交給今天的發言人、投資者關係主管 Lavina Talukdar。請繼續。

Thank you, Kevin. Good morning, and good afternoon, everyone. Thank you for joining today's call to discuss Moderna's second quarter 2025 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. On today's call are Stephane Bancel, our Chief Executive Officer; Stephen Hoge, our President; and Jamey Mock, our Chief Financial Officer.

謝謝你，凱文。大家早安，下午好。感謝您參加今天的電話會議，討論 Moderna 2025 年第二季的財務表現和業務更新。您可以造訪我們網站的「投資者」部分，查看今天早上發布的新聞稿以及我們將要審查的幻燈片。參加今天電話會議的有我們的執行長 Stephane Bancel、我們的總裁 Stephen Hoge 和我們的財務長 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》的安全港條款所作的前瞻性陳述。請參閱隨附簡報的第 2 張投影片和我們向美國證券交易委員會 (SEC) 提交的文件，以了解可能導致我們的實際業績和結果與這些前瞻性陳述中明示或暗示的業績和結果存在重大差異的重要風險因素。

With that, I'll now turn it over to Stephane.

現在，我將把發言權交給 Stephane。

Thank you, Lavina. Good morning, or good afternoon, everyone. Thank you for joining us today. I will start with a quick review of Q2. Jamey will present our financial results and outlook. Stephen will review our clinical programs, and then I will come back and share our key priorities and catalysts before we take your questions.

謝謝你，拉維娜。大家早安，或是下午好。感謝您今天加入我們。我首先對第二季度進行簡要回顧。Jamey 將介紹我們的財務表現和展望。史蒂芬將審查我們的臨床項目，然後我將回來分享我們的主要優先事項和催化劑，然後再回答您的問題。

Let me start with a review of our financials. In the second quarter, our revenues of $0.1 billion and a loss of $0.8 billion were in line with our expectations, and they reflect the highly seasonal nature of our Respiratory Vaccine business.

首先讓我回顧一下我們的財務狀況。第二季度，我們的收入為 1 億美元，虧損為 8 億美元，符合我們的預期，這反映了我們的呼吸道疫苗業務的高度季節性。

We ended the quarter with $7.5 billion in cash and investments. We remain highly focused on financial discipline. I'm very pleased to announce that continued cost reduction efforts across the company in the second quarter of 2025 led to a 35% reduction of cost of sales, R&D, and SG&A combined, compared to the second quarter of 2024. As you know, we are very focused on cash cost, and I'm happy to report that on a cash cost basis, we reduced operating expenses by $581 million in Q2 2025 versus Q2 2024, which is a 40% reduction year over year.

本季結束時，我們的現金和投資為 75 億美元。我們仍然高度重視財務紀律。我很高興地宣布，與 2024 年第二季相比，2025 年第二季全公司持續努力降低成本，導致銷售成本、研發成本和銷售、一般及行政費用合計降低了 35%。如您所知，我們非常關注現金成本，我很高興地報告，按現金成本計算，與 2024 年第二季度相比，我們在 2025 年第二季度的運營費用減少了 5.81 億美元，同比減少了 40%。

During the quarter, we made solid progress across our three strategic priorities. Priority one, driving use of our commercial products. We made strong progress in securing three approvals from the US FDA. On May 31, we were very pleased to announce the FDA approval of mNEXSPIKE, our next-generation COVID vaccine that has shown even higher efficacy than our Spikevax vaccine. In mid-June, we received FDA approval of our mRESVIA vaccine for high-risk individual aged 18 to 59.

本季度，我們在三大戰略重點上取得了紮實進展。第一要務是推動我們商業產品的使用。我們在獲得美國 FDA 三項批准方面取得了重大進展。5 月 31 日，我們非常高興地宣布 FDA 批准了我們的下一代 COVID 疫苗 mNEXSPIKE，功效甚至比我們的 Spikevax 疫苗更高。6 月中旬，我們的 mRESVIA 疫苗獲得了 FDA 批准，可用於治療 18 至 59 歲高風險族群。

As a reminder, we are also approved for adults 60 and older in the US and in 38 other countries. And in July, the FDA granted full approval of our Spikevax COVID vaccine for high-risk children aged 6 months through 11 years. This vaccine has previously been used under EUA. These approvals support our broader goal of driving use of our commercial products and driving the company back into sales growth.

提醒一下，我們也被批准在美國和其他 38 個國家為 60 歲及以上的成年人提供服務。7 月，FDA 全面批准我們的 Spikevax COVID 疫苗，適用於 6 個月至 11 歲的高風險兒童。該疫苗先前已在 EUA 下使用。這些批准支持了我們更廣泛的目標，即推動我們商業產品的使用並推動公司重新實現銷售成長。

On our second priority, advancing our pipeline to drive sales growth. We are very happy to announce positive and strong Phase III efficacy data for flu, which we believe will advance both our flu program and our flu plus COVID combination program. Stephen will discuss these results shortly.

我們的第二個優先事項是推動我們的通路以推動銷售成長。我們非常高興地宣布流感的 III 期積極且強勁的療效數據，我們相信這將推進我們的流感計劃以及流感加 COVID 組合計劃。史蒂芬將很快討論這些結果。

And our third priority, executing with financial discipline. The second quarter 2025 marked the fourth consecutive quarter where we've reduced combined R&D and SG&A expenses by double digits year over year. Additionally, in the second quarter, we expanded our cost reduction plan well beyond what we announced in the first quarter. We estimate that these measures will take an additional $400 million out of 2025 cost structure we previously laid out. This cost reduction includes a very difficult decision that we announced yesterday to reduce headcount by around 10% to better align Moderna cost structure and capabilities with current business conditions while also sustaining investments in our mRNA pipeline.

我們的第三項重點是嚴格執行財務紀律。2025 年第二季是我們連續第四個季度將研發和銷售、一般及行政費用總額比去年同期減少兩位數。此外，在第二季度，我們擴大了成本削減計劃，遠遠超出了第一季宣布的範圍。我們估計，這些措施將從我們先前製定的 2025 年成本結構中額外支出 4 億美元。這項成本削減包括一項非常艱難的決定，我們昨天宣布了裁員約 10% 的決定，以使 Moderna 的成本結構和能力更好地與當前業務狀況保持一致，同時維持對我們的 mRNA 管道的投資。

This decision was obviously not made lightly. It impacts people who have dedicated themselves to our mission, teammates, and friends who have built Moderna. I want to express, on behalf of the entire executive committee, our deepest thanks to all of those affected for what they have contributed to the company. These colleagues will always be part of the Moderna story.

顯然，這個決定並不是輕易做出的。它影響了那些致力於我們使命的人們、隊友以及創建 Moderna 的朋友。我謹代表整個執行委員會向所有受影響的人為公司所做的貢獻表示最深切的感謝。這些同事將永遠是 Moderna 故事的一部分。

Finally, before I hand to Jamey, you may have seen that in the last couple of hours, the UK Court of Appeal issued its decision. The court has decided to uphold the High Court's finding that Moderna's EP'949 patent is valid and infringed by Pfizer and BioNTech. Moderna will continue to pursue and enforce its patent rights globally to protect its innovative mRNA technology. Jamey?

最後，在我交給 Jamey 之前，您可能已經看到，在過去的幾個小時裡，英國上訴法院發布了判決。法院決定維持高等法院的裁定，認為 Moderna 的 EP'949 專利有效，並且遭到輝瑞和 BioNTech 的侵犯。Moderna 將繼續在全球範圍內尋求和執行其專利權，以保護其創新的 mRNA 技術。詹米？

Thanks, Stephane, and hello, everyone. Today, I'll cover our second-quarter financial results, our updated 2025 full-year outlook, and share our strategy to achieve our 2027 operating cost targets. Let's begin with our second-quarter financial results on slide 7. Net product sales were $114 million, primarily driven by COVID vaccine sales. The US accounted for approximately 80% of sales this quarter with the remainder from international markets. While product sales declined 38% compared to the second quarter of 2024, sales were slightly above our expectations due to a stronger-than-expected US spring booster season.

謝謝，史蒂芬，大家好。今天，我將介紹我們的第二季財務業績、最新的 2025 年全年展望，並分享我們實現 2027 年營運成本目標的策略。讓我們從幻燈片 7 上的第二季財務表現開始。淨產品銷售額為 1.14 億美元，主要受 COVID 疫苗銷售推動。本季美國約佔銷售額的 80%，其餘則來自國際市場。雖然產品銷售額與 2024 年第二季相比下降了 38%，但由於美國春季加強季節強於預期，銷售額略高於我們的預期。

We also recorded $28 million in other revenue, bringing total revenue to the quarter to $142 million. The year-over-year decline in other revenue was primarily driven by a $30 million upfront licensing payment that was recognized in the second quarter of last year. Cost of sales for the quarter was $119 million, which was relatively flat compared to $115 million last year. It represented 105% of net product sales this quarter, up from 62% in the prior year, driven primarily by lower volume.

我們還記錄了 2,800 萬美元的其他收入，使本季總收入達到 1.42 億美元。其他收入年減主要是因為去年第二季確認的 3,000 萬美元預付許可費用。本季銷售成本為 1.19 億美元，與去年的 1.15 億美元相比基本持平。它佔本季淨產品銷售額的 105%，高於去年同期的 62%，主要原因是銷量下降。

R&D expenses were $700 million in the second quarter, down 43% from last year. The decline was primarily driven by the wind down of our respiratory trials and lower clinical manufacturing costs. We also had year-over-year reductions in preclinical and external service costs, reflecting ongoing portfolio prioritization and productivity efforts. Last year's results also included an expense for a priority review voucher. SG&A expenses were $230 million for the quarter, down 14% year over year. The decrease reflects broad-based cost reductions across external services, personnel, and commercial activities as we continue to streamline operations and manage expenses with discipline.

第二季研發費用為7億美元，較去年同期下降43%。下降的主要原因是我們的呼吸試驗的減少和臨床製造成本的降低。我們的臨床前和外部服務成本也較去年同期下降，這反映了持續的投資組合優先化和生產力努力。去年的業績還包括優先審查券的費用。本季銷售、一般及行政費用為 2.3 億美元，較去年同期下降 14%。這一下降反映了我們繼續精簡營運並嚴格管理費用，從而降低了外部服務、人員和商業活動等方面的成本。

Our income tax provision for the quarter was immaterial, consistent with the prior year. We continue to maintain a global valuation allowance against the majority of our deferred tax assets, which limits our ability to recognize tax benefits for the quarter. Net loss for the quarter was $825 million, a $454 million improvement compared to a $1.3 billion loss in the second quarter of 2024. Loss per share was $2.13, an improvement from a loss of $3.33 in 2024. We ended Q2 with cash and investments of $7.5 billion, down from $8.4 billion at the end of Q1. The decrease was primarily driven by the operating loss for the quarter.

本季我們的所得稅準備金並不重要，與前一年一致。我們繼續對大部分遞延稅務資產維持全球估值準備金，這限制了我們確認本季稅務優惠的能力。本季淨虧損為 8.25 億美元，較 2024 年第二季的 13 億美元虧損改善了 4.54 億美元。每股虧損為 2.13 美元，較 2024 年的 3.33 美元虧損有所改善。我們第二季末的現金和投資為 75 億美元，低於第一季末的 84 億美元。下降的主要原因是本季的經營虧損。

Moving to slide 8. I will share our updated 2025 financial framework. For total revenue, we are updating our 2025 projected revenue range to $1.5 billion to $2.2 billion, reflecting a $300 million reduction at the high end. This change is primarily due to a timing shift of UK COVID shipments from the second half of 2025 into the first quarter of 2026. The timing shift for the UK shipments is due to the government's use of their fiscal year minimum purchase -- product purchase for the spring campaign in 2026. So our deliveries will now deliver in 1Q 2026. This represents the vast majority of the $300 million impact. Importantly, the timing shift does not impact the total value of our long-term multiyear contract with the UK government.

移至幻燈片 8。我將分享我們更新的2025年財務框架。總收入，我們將 2025 年預計收入範圍更新為 15 億美元至 22 億美元，最高減少 3 億美元。這項變更主要是由於英國 COVID 出貨時間從 2025 年下半年推遲到 2026 年第一季。英國出貨時間的轉變是由於政府使用了其財政年度最低購買量——即 2026 年春季活動的產品購買量。因此我們的交付將於 2026 年第一季完成。這佔了 3 億美元影響的絕大部分。重要的是，時間的轉變不會影響我們與英國政府簽訂的長期多年合約的總價值。

Our updated revenue range continues to reflect the uncertainties in vaccination rates, the competitive market environment, the size of the RSV market, and timing of licensure of our factories and product approvals in Australia and Canada. On a geographic basis, we are updating US product sales -- we are expecting US product sales of $1.0 billion to $1.5 billion, international product sales of $0.4 billion to $0.6 billion, and other revenues of approximately $100 million, where the majority is international.

我們更新的收入範圍繼續反映疫苗接種率、競爭激烈的市場環境、呼吸道合胞病毒市場的規模以及我們在澳洲和加拿大的工廠許可和產品批准時間的不確定性。從地理角度來看，我們正在更新美國產品銷售額——我們預計美國產品銷售額為 10 億至 15 億美元，國際產品銷售額為 4 億至 6 億美元，其他收入約為 1 億美元，其中大部分來自國際市場。

For US product sales of $1.0 billion to $1.5 billion, the high end of the range assumes flat year-over-year performance after adjusting for last year's $200 million prior period return reserve reversal. The low end of the range factors the potential combined impacts from lower vaccination rates and competitive market pressures.

對於銷售額在 10 億美元至 15 億美元的美國產品，該範圍的高端假設是在調整去年 2 億美元的前期退貨準備金沖銷後，業績與去年同期持平。該範圍的低端因素考慮了較低疫苗接種率和競爭市場壓力的潛在綜合影響。

For international product sales of $0.4 billion to $0.6 billion, the low end of the range is mainly from secured contracts, while the high end factors in incremental revenue from active tenders. The net range now also reflects the shift in shipments for the UK from the second half of 2025 to the first quarter of 2026. For other revenues of $100 million, we've already recognized $50 million in the first half of the year and expect a similar amount in the second half. The majority of the revenue is associated with our new manufacturing sites but also includes some grant, collaboration, licensing, and royalty revenue.

對於 4 億美元至 6 億美元的國際產品銷售額，低端主要來自已簽訂的合同，而高端則考慮了來自積極投標的增量收入。現在的淨範圍也反映了英國從 2025 年下半年到 2026 年第一季的出貨量變化。對於 1 億美元的其他收入，我們已經在上半年確認了 5,000 萬美元，預計下半年也將實現類似的金額。大部分收入與我們的新製造工廠有關，但也包括一些補助、合作、授權和特許權使用費收入。

The split of our 3Q and 4Q revenue mix will be dependent on timing of regulatory approvals across the world and the number of days available to ship in the third quarter. We expect the revenue split of 40% to 50% in Q3 with the balance in Q4. Our cost of sales estimate of $1.2 billion remains unchanged and reflects year-over-year improvements in manufacturing efficiency, offset by increased costs associated with the go-live of our new international manufacturing sites. Newly introduced tariffs are not expected to have a material impact on our cost of sales. We continue to monitor changes to global tariffs.

我們的第三季和第四季收入結構分佈將取決於全球監管部門的批准時間以及第三季可出貨的天數。我們預計第三季的營收分成將為 40% 至 50%，剩餘部分將在第四季實現。我們的銷售成本估計為 12 億美元，保持不變，反映了製造效率的同比提高，但被我們新的國際製造基地投入使用所帶來的成本增加所抵消。新推出的關稅預計不會對我們的銷售成本產生重大影響。我們持續關注全球關稅的變化。

We are lowering our R&D expense forecast from $4.1 billion to a range of $3.6 billion to $3.8 billion due to Phase III trial wind-downs, continued portfolio prioritization, and productivity. Our revised R&D guidance projects an increase in the second half versus the first half, driven by the seasonality of vaccine spend as well as studies in support of regulatory approvals.

由於第三階段試驗的結束、持續的投資組合優先排序和生產力，我們將研發費用預測從 41 億美元下調至 36 億美元至 38 億美元之間。我們修訂後的研發指南預測下半年的研發支出將比上半年增加，這主要是由於疫苗支出的季節性以及支持監管部門批准的研究。

SG&A expenses are still expected to be $1.1 billion. Similar to last year, we expect higher SG&A expenses in the second half of the year, primarily due to commercial-related activity, but also due to severance charges associated with the workforce reduction we announced yesterday. We expect taxes to be negligible in 2025. Our capital expenditures projection has been lowered from $400 million down to $300 million due to our continued prioritization and efficiency gains. We still expect to end 2025 with approximately $6 billion in cash and investments.

預計銷售、一般及行政費用仍為 11 億美元。與去年類似，我們預計下半年銷售、一般及行政費用將會增加，這主要是由於商業相關活動，但也與我們昨天宣布的裁員相關的遣散費有關。我們預計 2025 年的稅收將可以忽略不計。由於我們持續的優先排序和效率提升，我們的資本支出預測已從 4 億美元下調至 3 億美元。我們仍預計到 2025 年底，現金和投資將達到約 60 億美元。

Moving to slide 9. As discussed on last quarter's call, we are planning a total reduction in annual GAAP operating expenses of over $6 billion from $11 billion in 2023 to $5 billion or less in 2027. On a cash cost basis, which excludes stock-based compensation, depreciation, and amortization, we are decreasing annual operating expenses from $8.9 billion in 2023 to our midpoint target of $4.2 billion in 2027, which is a reduction of over 50%.

移至幻燈片 9。正如上個季度電話會議上所討論的那樣，我們計劃將年度 GAAP 營運費用總計減少 60 多億美元，從 2023 年的 110 億美元減少到 2027 年的 50 億美元或更少。以現金成本計算（不包括股票薪酬、折舊和攤提），我們將年度營運費用從 2023 年的 89 億美元減少到 2027 年的中點目標 42 億美元，降幅超過 50%。

Our revised 2025 GAAP operating expense range is now $5.9 billion to $6.1 billion, a $400 million reduction at the midpoint from our previous guidance of $6.4 billion. This updated guidance puts us on track to achieve the first $5 billion of our overall $6 billion reduction in annual GAAP expenses in two years. Our updated 2025 guidance includes $0.9 billion of non-cash expenses from stock-based compensation, depreciation, and amortization. Excluding those non-cash items, we now project a 2025 cash cost of approximately $5.1 billion. At the midpoint of the range, a $400 million reduction from our previous cash cost estimate of $5.5 billion.

我們修訂後的 2025 年 GAAP 營運費用範圍現為 59 億美元至 61 億美元，比我們先前預測的 64 億美元減少了 4 億美元。這項更新後的指引使我們預計在兩年內實現年度 GAAP 費用削減總額 60 億美元中的第一個 50 億美元。我們更新的 2025 年指引包括 9 億美元的股票薪酬、折舊和攤提非現金支出。不包括這些非現金項目，我們現在預計 2025 年的現金成本約為 51 億美元。以該範圍的中間值，比我們先前估計的 55 億美元現金成本減少了 4 億美元。

The strong progress in cost reductions to date has been a company-wide effort. While we continue to drive additional cost reductions in all areas, the largest source of future reductions will come from R&D, which represents over 60% of our cost base.

迄今為止，成本削減方面取得的顯著進展是全公司共同努力的結果。雖然我們將繼續在各個領域進一步削減成本，但未來削減的最大來源將來自研發，這占我們成本基礎的 60% 以上。

On the next slide, I want to share our strategy to achieve our 2027 operating expense targets in more detail. On slide 10, you can see our GAAP and cash cost targets for 2025 versus 2027. At the midpoint of our ranges, we are targeting a $1.1 billion GAAP cost reduction from $6 billion in '25 to $4.9 billion in '27 and a $900 million cash cost reduction from $5.1 billion in '25 to $4.2 billion in '27.

在下一張投影片中，我想更詳細地分享我們實現 2027 年營運費用目標的策略。在第 10 張投影片上，您可以看到我們 2025 年和 2027 年的 GAAP 和現金成本目標。按照我們設定的中間值，我們的目標是將 GAAP 成本從 25 年的 60 億美元削減 11 億美元至 27 年的 49 億美元，並將現金成本從 25 年的 51 億美元削減 9 億美元至 27 年的 42 億美元。

There are four primary drivers to achieve this goal, which are all relatively evenly split in impact. First, a reduction in R&D expenses from the completion of our large Phase III trials. We are already seeing the impact of the completion of most of our respiratory trials in 2025, and we'll start to see future cost savings by 2027 from the completion of our Phase III trials for CMV and norovirus. This includes both direct trial costs as well as reductions in clinical manufacturing and other related overheads. These cost reductions will be partially offset by select investments in the pipeline, such as our oncology portfolio.

要實現這一目標有四個主要驅動力，其影響力都相對均衡。首先，完成大規模 III 期試驗後，研發費用減少。我們已經看到了 2025 年完成大部分呼吸道試驗的影響，並且到 2027 年，隨著 CMV 和諾羅病毒 III 期試驗的完成，我們將開始看到未來的成本節約。這包括直接試驗成本以及臨床製造和其他相關開銷的減少。這些成本的降低將部分被正在進行的精選投資所抵消，例如我們的腫瘤學產品組合。

Second, we will continue to drive manufacturing efficiencies, which will impact both cost of sales and R&D. We have already made strong progress over the past few years to optimize our manufacturing footprint from endemic level demand of our COVID vaccine. We expect to drive additional savings through process improvements as well as reductions in future inventory write-downs. For example, in 2024, we had $0.5 billion of inventory write-downs, which we are actively driving to reduce in 2025 and beyond.

其次，我們將持續提高製造效率，這將影響銷售成本和研發成本。過去幾年來，我們已經取得了長足的進步，根據 COVID 疫苗的地方性需求優化了我們的生產佈局。我們希望透過流程改進以及減少未來的庫存減記來實現額外的節省。例如，2024 年我們的庫存減記金額為 5 億美元，我們正在積極推動在 2025 年及以後減少這一數字。

Third, we continue to drive procurement savings. Some of the savings from the renegotiated contracts already taken place will not be fully realized until 2026. Additionally, we have a strong pipeline of new savings initiatives.

第三，我們持續推動採購節約。已經重新談判的合約所帶來的部分節省要到 2026 年才能完全實現。此外，我們還有一系列新的節約措施。

Fourth, we announced a workforce restructuring yesterday that impacts approximately 10% of our employees and will lower our employee base to under 5,000 by the end of the year versus 5,800 at the beginning of the year. Headcount reductions are always difficult decisions as they impact valued colleagues have contributed meaningfully to our mission. However, these actions are necessary to reshape our capabilities and align to our long-term operating cost structure.

第四，我們昨天宣布了一項勞動力重組計劃，該計劃將影響約 10% 的員工，到年底，我們的員工人數將從年初的 5,800 人減少到 5,000 人以下。裁員始終是一個艱難的決定，因為它會影響那些為我們的使命做出有意義貢獻的寶貴同事。然而，這些行動對於重塑我們的能力並適應我們的長期營運成本結構是必要的。

In summary, in just two years, the team has made tremendous progress towards our four-year roughly $5 billion cash cost reduction plan. By the end of 2025, we have taken nearly $4 billion of cost out of the business and have an achievable plan to remove another $1 billion over the next two years. We remain committed to breaking even on a cash cost basis in 2028 and will adjust spending as necessary.

總而言之，在短短兩年內，團隊在我們為期四年約 50 億美元的現金成本削減計畫方面取得了巨大進展。到 2025 年底，我們已從業務中削減了近 40 億美元的成本，並製定了可行的計劃，在未來兩年內再削減 10 億美元。我們仍致力於在 2028 年實現現金成本收支平衡，並將根據需要調整支出。

With that, I will now turn the call over to Stephen.

說完這些，我現在將電話轉給史蒂芬。

Thank you, Jamey, and good morning, or good afternoon, everyone. Today, I'll review progress across our pipeline. Slide 12 is a review of our prioritized pipeline. As Stephane stated earlier, we have announced significant updates for many of these programs, including the recent approval for mNEXSPIKE, an expanded label for mRESVIA, and approval of our pediatric Spikevax COVID vaccine, which was previously available in the United States under an emergency use authorization.

謝謝你，Jamey，大家早安，或下午好。今天，我將回顧我們整個管道的進展。投影片 12 是對我們的優先管道的回顧。正如 Stephane 之前所說，我們宣布了許多此類項目的重要更新，包括最近批准的 mNEXSPIKE、mRESVIA 的擴展標籤以及我們兒科 Spikevax COVID 疫苗的批准，該疫苗之前在美國根據緊急使用授權可用。

In the quarter, we also reported strong vaccine efficacy results from our Phase III seasonal flu trial, and we continue to make progress in the rest of the prioritized portfolio, where we are targeting a total of additional potential filings through 2028.

本季度，我們也報告了 III 期季節性流感試驗的疫苗有效性結果，並且我們繼續在其餘優先投資組合中取得進展，我們的目標是到 2028 年總共提交更多潛在申請。

Moving to slide 13, which outlines the latest developments of our late-stage Respiratory portfolio. I'll start with our COVID vaccine, Spikevax and the mNEXSPIKE. As mentioned earlier, we are very pleased with the FDA's approval of the mNEXSPIKE our next-generation COVID vaccine, which has shown strong relative vaccine efficacy compared to Spikevax in its Phase III trial, including in the 65 and older age subgroup and in those with risk factors for severe COVID-19.

前往第 13 張投影片，其中概述了我們後期呼吸產品組合的最新發展。我先從我們的 COVID 疫苗 Spikevax 和 mNEXSPIKE 開始。如前所述，我們對 FDA 批准我們的下一代 COVID 疫苗 mNEXSPIKE 感到非常高興，該疫苗在 III 期試驗中與 Spikevax 相比表現出了強大的相對疫苗有效性，包括在 65 歲及以上的年齡組和具有嚴重 COVID-19 風險因素的人群中。

mNEXSPIKE was approved in the US for individuals 65 and older and for people 12 to 64 with at least one risk factor. An extensive analysis of the Phase III clinical data for mNEXSPIKE was published last month in The Lancet, and the link to the publication can be found on this slide.

mNEXSPIKE 在美國已獲批准，適用於 65 歲及以上的個人以及至少有一個風險因素的 12 至 64 歲人群。上個月，《柳葉刀》雜誌發表了對 mNEXSPIKE 第三階段臨床數據的廣泛分析，該出版物的連結可在此幻燈片上找到。

We submitted the annual updates for our COVID-19 vaccines for the currently recommended LP.8.1 strain in the quarter and expect mNEXSPIKE and Spikevax will be available this fall in the United States. Speaking of Spikevax, the vaccine was recently approved by the FDA for high-risk children ages 6 months to 11 years. Spikevax had previously been available to this age group in the US only under an emergency use authorization. Earlier this week, Spikevax also received EMA approval for the current season update LP.8.1 strain update for the coming season.

我們在本季提交了目前推薦的 LP.8.1 株的 COVID-19 疫苗年度更新，預計 mNEXSPIKE 和 Spikevax 將於今年秋季在美國上市。說到Spikevax，該疫苗最近已獲得FDA批准，可用於6個月至11歲的高風險兒童。此前，Spikevax 僅在緊急使用授權下才在美國提供給該年齡層。本週早些時候，Spikevax 還獲得了 EMA 批准，可將當前季節更新的 LP.8.1 病毒株更新用於下一季。

For RSV, our mRESVIA vaccine was approved by the FDA on June 12 for individuals ages 18 to 59 with at least one risk factor. The CDC subsequently adopted the ACIP recommendation for the 50- to 59-year old age cohort in this group, which means that recommendations for our vaccine are now consistent with competitors.

對於 RSV，我們的 mRESVIA 疫苗於 6 月 12 日獲得 FDA 批准，適用於年齡 18 至 59 歲且至少有一個風險因素的個人。隨後，CDC 採納了 ACIP 針對該群體中 50 至 59 歲年齡組的建議，這意味著我們疫苗的建議現在與競爭對手一致。

For our seasonal flu vaccine, we announced positive results from our Phase III efficacy study. We are very pleased with the results, which I'll talk through on the next slide. We expect these flu results will also support our discussions with regulators about our flu plus COVID combination vaccine, and we have begun consultations with regulators on the submission requirements for both vaccines.

對於我們的季節性流感疫苗，我們公佈了第三階段療效研究的積極成果。我們對結果非常滿意，我將在下一張投影片中詳細討論。我們預計這些流感結果也將支持我們與監管機構就流感加 COVID 聯合疫苗進行的討論，並且我們已經開始就這兩種疫苗的提交要求與監管機構進行磋商。

On slide 14, I will discuss the very encouraging P304 flu vaccine efficacy data released during the quarter. In this 40,000-person study conducted across 11 countries, our seasonal flu vaccine, mRNA-1010, demonstrated relative vaccine efficacy that was 26.6% higher than the licensed standard dose comparator in adults aged 50 and above. Safety and tolerability of mRNA-1010 were consistent with previously reported Phase III results, and the majority of solicited adverse reactions were mild.

在第 14 張投影片上，我將討論本季發布的非常令人鼓舞的 P304 流感疫苗功效數據。在這項涵蓋 11 個國家的 40,000 人的研究中，我們的季節性流感疫苗 mRNA-1010 顯示出比 50 歲及以上成年人的許可標準劑量對照劑高出 26.6% 的相對疫苗有效性。mRNA-1010 的安全性和耐受性與先前報告的 III 期結果一致，且大多數徵集到的不良反應都是輕微的。

Importantly, strong relative vaccine efficacy was observed for all three influenza strains contained in the vaccine, including H1N1, H3N2 and the B/Victoria strain. Likewise, the relative vaccine efficacy was consistently strong across age groups, risk factors, and previous vaccination status. In the important 65 and older demographic relative vaccine efficacy was a strong 27.4%.

重要的是，疫苗中所含的所有三種流感病毒株（包括 H1N1、H3N2 和 B/Victoria 病毒株）都具有較強的相對疫苗效力。同樣，無論年齡層、危險因子或先前的疫苗接種狀況，疫苗的相對效力始終很強。在重要的 65 歲及以上族群中，疫苗相對有效性高達 27.4%。

We look forward to presenting these data at an upcoming medical conference, and we are preparing to file for FDA approval for this vaccine.

我們期待在即將舉行的醫學會議上展示這些數據，並且我們正在準備向 FDA 申請該疫苗的批准。

Now turning to our Non-respiratory Vaccine and Rare Disease portfolios. In our Phase III CMV efficacy study for mRNA-1647, we have now accrued sufficient primary endpoint cases for the final analysis. The analysis has not yet been conducted, and the company remains fully blinded at this time. We've submitted an amendment to the analysis plan to add important powered secondary endpoints that we hope will increase the scientific value of the results. Once the updated analysis plan is formalized, we will proceed with the analysis of primary and secondary endpoints, which we expect to complete in the fall.

現在轉向我們的非呼吸道疫苗和罕見疾病產品組合。在我們對 mRNA-1647 進行的 III 期 CMV 功效研究中，我們現在已經累積了足夠的主要終點病例，可以進行最終分析。分析尚未進行，目前該公司仍完全不知情。我們已經提交了分析計劃的修正案，以添加重要的有依據的次要終點，我們希望這將增加結果的科學價值。一旦更新後的分析計劃正式確定，我們將繼續進行主要和次要終點的分析，預計在秋季完成。

Our Phase III norovirus study is now accruing cases in its first season. As with other studies, the interim analysis of efficacy is dependent on case accrual. And depending upon the rate case accrual, the study has been designed so that it may proceed to a second season of enrollment if necessary.

我們的第三階段諾羅病毒研究目前正在第一季累積病例。與其他研究一樣，療效的中期分析取決於病例的累積。根據案例累積率，該研究已設計為必要時可進入第二季的招生。

In Rare Diseases, our propionic acidemia or PA program is currently in a registrational study, and we believe we are on track for a potential 2027 approval. For methylmalonic acidemia, or MMA, we plan to initiate the registrational trial this year.

在罕見疾病領域，我們的丙酸血症或 PA 計畫目前正在進行註冊研究，我們相信我們預計在 2027 年獲得批准。對於甲基丙二酸血症（MMA），我們計劃今年啟動註冊試驗。

We continue to advance our Oncology portfolio, with significant progress across our individualized neoantigen therapy, known as Intismeran, mRNA-4359 previously called Checkpoint, and our early-stage oncology pipeline. In collaboration with Merck, we have several late-stage studies underway for Intismeran. As a reminder, the Phase III trial in adjuvant melanoma is fully enrolled and accruing cases towards its interim analysis. Our Phase II adjuvant renal cell carcinoma trial is fully enrolled as well.

我們繼續推進我們的腫瘤學產品組合，我們的個人化新抗原療法（稱為 Intismeran）、mRNA-4359（以前稱為 Checkpoint）以及我們的早期腫瘤學管線取得了重大進展。我們與默克公司合作，對 Intismeran 進行了多項後期研究。提醒一下，輔助性黑色素瘤的 III 期試驗已完全招募完畢，並且正在累積病例以進行中期分析。我們的 II 期輔助性腎細胞癌試驗也已全部招募完畢。

And as we have disclosed previously, we have two Phase III studies in non-small cell lung cancer, one Phase II study in high-risk muscle-invasive bladder cancer, and one Phase II study in high-risk non-muscle invasive bladder cancer. We have also expanded our Intismeran program into a Phase II study in first-line metastatic melanoma. This could be the first of many studies using Intismeran and KEYTRUDA together in metastatic indications. Following on from Intismeran, mRNA-4359 is now in a Phase II study in first-line metastatic melanoma and first-line metastatic non-small cell lung cancer. And we are currently enrolling patients in the lung cancer portion of that study.

正如我們先前所揭露的，我們有兩項針對非小細胞肺癌的 III 期研究、一項針對高風險肌肉層浸潤性膀胱癌的 II 期研究，以及一項針對高風險非肌肉層浸潤性膀胱癌的 II 期研究。我們也將 Intismeran 計畫擴展為針對第一線轉移性黑色素瘤的 II 期研究。這可能是眾多使用 Intismeran 和 KEYTRUDA 合併治療轉移性適應症的研究中的第一項。繼 Intismeran 之後，mRNA-4359 目前正處於第一線轉移性黑色素瘤和第一線轉移性非小細胞肺癌的 II 期研究階段。我們目前正在招募研究的肺癌部分患者。

We are pleased that the data from the Phase Ib study of mRNA-4359 plus KEYTRUDA in Checkpoint inhibitor refractory PD-L1 positive patients was accepted as a mini oral presentation at ESMO. We look forward to presenting these findings at the meeting in October.

我們很高興，mRNA-4359 合併 KEYTRUDA 在檢查點抑制劑難治性 PD-L1 陽性患者的 Ib 期研究數據被 ESMO 接受為迷你口頭報告。我們期待在十月的會議上展示這些調查結果。

In early-stage oncology, we are also dosing patients in our Phase I tumor-targeted antigen therapy, mRNA-4106; and the INDs for our cell therapy enhancing engine therapy, mRNA-4203; and our T cell engager, mRNA-2808 are also now both open. We are pleased by our growing oncology pipeline and the continued strong momentum of the large Intismeran clinical trial program in partnership with Merck.

在早期腫瘤學中，我們也正在為患者提供 I 期腫瘤標靶抗原療法 mRNA-4106 的給藥；我們的細胞療法增強引擎療法 mRNA-4203 的 IND；以及我們的 T 細胞接合器 mRNA-2808 的 IND 現在也都已開放。我們對不斷成長的腫瘤學產品線以及與默克合作的大型 Intismeran 臨床試驗計畫持續強勁的發展勢頭感到高興。

With that, I'll hand over to Stephane.

說完這些，我就把麥克風交給史蒂芬 (Stephane)。

Thank you, Stephen and Jamey. As you know, we have three priorities: priority one, drive sales of approved products; priority two, focus on our late-stage pipeline, where we can drive product growth for approvals; and priority thee, delivering on our cost efficiency across the company. Our first priorities will drive use of mNEXSPIKE, Spikevax, and mRESVIA vaccines. We entered the third quarter of 2025 with three approved products in the US, and we are seeing a growing number of approvals in countries worldwide.

謝謝你，史蒂芬和傑米。如您所知，我們有三個優先事項：第一，推動已獲批准產品的銷售；第二，專注於我們的後期研發管線，我們可以藉此推動產品成長以獲得批准；第三，實現全公司的成本效率。我們的首要任務是推動 mNEXSPIKE、Spikevax 和 mRESVIA 疫苗的使用。進入 2025 年第三季度，美國已有三種產品獲批，我們看到世界各國獲批的產品數量也不斷增加。

For priority two, we are focused on delivering up to 10 products approval, which we believe will drive sales growth for the company. Together, these 10 anticipated products target an addressable market that is over $30 billion. In Q2, we secured US approvals for mNEXSPIKE and mRESVIA for (inaudible) people, and which are exciting data in flu, enabling flu and flu-COVID combo.

對於第二個優先事項，我們專注於提供多達 10 種產品的批准，我們相信這將推動公司的銷售成長。總而言之，這 10 款預期產品的目標市場規模超過 300 億美元。在第二季度，我們獲得了美國對（聽不清楚）人群的 mNEXSPIKE 和 mRESVIA 的批准，這是有關流感的令人興奮的數據，可以實現流感和流感-COVID 組合。

On the cost side of the house, we've demonstrated our commitment to cost discipline to the reduction achieved in last year in 2024 and also in 2025 to date. We remain confident in our ability to further streamline our operational structure for the remaining of '25 to 2027. CMV just took you through our plans to cut an additional $400 million of our 2025 cost structure, and we are not done. We have many new projects in the works to reduce cost further.

在成本方面，我們已經證明了我們對成本控制的承諾，並在去年、2024 年和 2025 年至今實現了成本削減。我們仍然有信心，我們有能力在 2025 年剩餘時間到 2027 年期間進一步精簡我們的營運結構。CMV 剛剛向您介紹了我們削減 2025 年成本結構中額外 4 億美元的計劃，但我們還沒有完成。我們正在進行許多新項目以進一步降低成本。

These cost reduction activities we have in place gives us even greater confidence in our plan to reduce our cash cost to $4.2 billion in 2027. These actions are very important to help us achieve our cash breakeven targets in 2028.

我們實施的這些成本削減活動使我們對在 2027 年之前將現金成本削減至 42 億美元的計畫更有信心。這些行動對於幫助我們實現2028年的現金損益平衡目標非常重要。

As we make these cost improvements, we are seeing continued use of AI across Moderna. We rolled out GPT Enterprise in 2024 and established widespread GPT literacy across the entire organization. Today, 100% of our knowledge workers are active daily users of ChatGPT.

隨著我們進行這些成本改進，我們看到 Moderna 正在繼續使用人工智慧。我們於 2024 年推出了 GPT Enterprise，並在整個組織內建立了廣泛的 GPT 素養。如今，我們 100% 的知識工作者都是 ChatGPT 的日常活躍用戶。

As you can see on slide 22, GPT users have grown very fast at the company. And in 2025, we enhanced AI tools to allow for deep research capabilities allowing for the creation of comprehensive report without compromised quality of output. An example of a deep research application is the creation of target product profiles. This AI-based activity greatly reduces the amount of time it takes on product planners to create marketing strategies.

正如您在第 22 張投影片上看到的，GPT 用戶在公司內成長非常快。2025 年，我們將增強人工智慧工具，以實現深入研究能力，從而能夠在不影響輸出品質的情況下創建全面的報告。深度研究應用的一個例子是建立目標產品概況。這種以人工智慧為基礎的活動大大減少了產品規劃人員制定行銷策略所需的時間。

We're excited about how AI has already improved our business. And given the doubling of AI capabilities every six to seven months, we are working hard to continue to reinvent our company across each business process, department, and team. We're excited about the coming months and quarters as we have a lot of important catalysts. First, of course, the potential approvals of seasonal flu and the flu + COVID programs based on the data Stephen shared with you. We're also eager to get the CMV Phase III efficacy data later this year. Norovirus Phase III readout is, of course, subject to gas accruals.

我們很高興看到人工智慧已經改善了我們的業務。鑑於人工智慧能力每六到七個月就會翻一番，我們正在努力繼續重塑公司的每個業務流程、部門和團隊。我們對未來幾個月和幾個季度感到興奮，因為我們有很多重要的催化劑。首先，當然，根據史蒂芬與您分享的數據，季節性流感和流感+ COVID 計劃可能會獲得批准。我們也渴望在今年稍後獲得 CMV 第三階段療效數據。當然，諾羅病毒第三階段的讀數取決於氣體的累積。

In Oncology, we look forward to the readout of our ongoing Intismeran Phase II five-year durability data in adjuvant melanoma. And of course, we look forward to a Phase III adjuvant melanoma trial readout for (inaudible).

在腫瘤學方面，我們期待讀取我們正在進行的 Intismeran II 期輔助黑色素瘤五年耐久性數據。當然，我們期待 III 期輔助性黑色素瘤試驗結果（聽不清楚）。

As Stephen said in oncology, we are looking forward to sharing the Checkpoint Phase Ib data at ESMO in Berlin in October. And as (inaudible), we look forward to sharing the Phase II data of this program. PA is already in restriction study, and MMA will be very soon.

正如腫瘤學領域的 Stephen 所說，我們期待 10 月在柏林的 ESMO 上分享 Checkpoint Ib 期數據。並且（聽不清楚），我們期待分享該計劃的第二階段數據。PA 已處於限制研究中，而 MMA 也將很快進入限制研究階段。

I'm pleased with the progress we have made on all three of our priorities over the course of the first six months of the year. We now have three products approved by the US FDA. We are highly encouraged about the progress in the pipeline and very pleased by [approval]. In our financial discipline, we have accelerated our plan for cost efficiency and expect to deliver an additional $400 million of cost savings this year.

我很高興看到我們在今年前六個月在所有三個優先事項上都取得了進展。我們目前有三種產品獲得美國FDA批准。我們對管道的進展感到非常鼓舞，並且非常高興[贊同]。在我們的財務紀律方面，我們加快了成本效率計劃，預計今年將額外節省 4 億美元的成本。

I want to thank the team for all the great work that was done this quarter. We are very focused on executing those priorities going forward. This work allows to be focused on our mission: to deliver the greatest possible impact to people through mRNA medicine.

我要感謝團隊本季所做的所有出色工作。我們非常注重今後執行這些優先事項。這項工作使我們能夠專注於我們的使命：透過 mRNA 藥物為人們帶來盡可能大的影響。

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

接線員，我們很樂意回答您的問題。

(Operator Instructions) Salveen Richter, Goldman Sachs.

（操作員指示）高盛的 Salveen Richter。

I was wondering if you could put the changes to CMV in context for us and just help us understand the rationale behind the addition of the secondary end points. And then secondly, as we look to the individualized neoantigen therapy, and I know we're going to data at ESMO. Could you help us understand the cadence of data reads over maybe the next 12 months or so as we look to some of the other programs to mature? Thank you.

我想知道您是否可以為我們介紹 CMV 的變化，並幫助我們理解添加次要終點背後的理由。其次，當我們研究個人化新抗原治療時，我知道我們將在 ESMO 上獲得數據。當我們期待其他一些專案日趨成熟時，您能否幫助我們了解未來 12 個月左右資料讀取的節奏？謝謝。

Thank you, Salveen. So first on CMV secondary endpoints. Obviously, we're pleased to now have sufficient primary endpoint cases, which, as you know, were based on primary prevention of infection in immunogenicity implants, so antibodies against antigens not the vaccine. But there's a lot of other data that will help inform the potential value of a CMV vaccine, including looking at things like the presence of virus in bottling fluids and/or other markers or measures of infection that could be quite relevant for the use of the CMV vaccine across a wider range of populations, including even in the congenital CMV space.

謝謝你，薩爾文。首先討論 CMV 次要終點。顯然，我們很高興現在有足夠的主要終點病例，如您所知，這些病例是基於免疫原性植入物感染的一級預防，因此是針對抗原的抗體，而不是疫苗。但還有很多其他數據可以幫助了解 CMV 疫苗的潛在價值，包括觀察瓶裝液體中病毒的存在和/或其他感染標記或測量指標，這些數據可能與在更廣泛人群中使用 CMV 疫苗非常相關，甚至包括在先天性 CMV 領域。

Given that this is now the final analysis and as we've accrued a large number of cases and a lot of data, including against some of those secondary potential end points, we want to make sure that we reflected those in the final analysis plan as we hope that we will see a positive primary endpoint and also get the benefit of some of those secondary powered endpoints in the totality of data that would come out of the study.

鑑於這是最終分析，並且我們已經累積了大量案例和數據，包括針對一些次要潛在終點的數據，我們希望確保在最終分析計劃中反映這些情況，因為我們希望看到積極的主要終點，並且從研究得出的全部數據中獲得一些次要有力終點的益處。

I'll just remind you again that the best approach for doing this is while we are completely blinded. So the company does not know the results on the primary or any of the secondary. We are just making sure to protect the integrity of the study that we update the scale analysis plan and receive approvals for it prior to initiating that analysis with an unblinded team at which point we would then become unblinded the results after the DSMB.

我只是想再次提醒你，實現這一目標的最佳方法是在我們完全失明的情況下。因此，該公司不知道主要結果或任何次要結果。我們只是確保保護研究的完整性，我們會更新量表分析計劃，並在與非盲團隊啟動分析之前獲得批准，此時我們將在 DSMB 之後公佈結果。

And so this is just making sure we're protecting the integrity of the study. And we think it's a prudent decision to take a little bit of time here to update all those documents prior to conducting the analysis. Really look forward to that result in the fall. As it relates to the cadence of results on Intismeran, we're fully enrolled in the Phase III, as we noted, for the confirmatory study in melanoma. We are accruing events. We continue to hope that we will be able to have a successful interim analysis for efficacy on that study on the timelines we previously mentioned.

因此，這只是為了確保我們保護研究的完整性。我們認為，在進行分析之前花一點時間更新所有這些文件是一個明智的決定。真的很期待秋天的結果。由於它與 Intismeran 的結果節奏有關，正如我們所指出的，我們已完全參與了黑色素瘤驗證性研究的第三階段。我們正在累積事件。我們仍然希望能夠按照我們之前提到的時間表對該研究的有效性進行成功的中期分析。

We have a number of other studies that are randomized. Actually, all of the Phase III and Phase II studies are randomized controlled studies. And several of those could read out similarly in the near term, including the studies in bladder cancer, particularly those that are largely enrolled as well as renal cell carcinoma. So those are event driven.

我們還有許多其他隨機研究。實際上，所有 III 期和 II 期研究都是隨機對照研究。其中一些研究可能在短期內得到類似的結果，包括膀胱癌研究，特別是那些大量招募的研究以及腎細胞癌研究。這些都是事件驅動的。

And so as is always the case for events studies, it's hard for us to predict exactly when we'll have sufficient data to conduct those interim analyses. But I do believe that in the coming year or two, there will be a consistent cadence of results from these randomized studies that will come out, hopefully first with a successful Phase III adjuvant melanoma study, but really soon thereafter with some of these Phase IIs and then moving into the lung cancer space.

因此，就像事件研究的情況一樣，我們很難準確預測何時才能有足夠的數據來進行這些中期分析。但我確實相信，在未來一兩年內，這些隨機研究將會陸續出爐，希望首先能成功完成 III 期輔助性黑色素瘤研究，但不久後將完成一些 II 期研究，然後進入肺癌領域。

Eliana Merle, UBS.

瑞銀的 Eliana Merle。

Can you discuss how we should think about pricing for the COVID vaccine in the US this year and what your expectations are for net price? Or I guess, how pricing this year would compare versus last year? And any takeaways from your contracting discussions so far? Thanks.

您能否討論一下我們應該如何考慮今年美國 COVID 疫苗的定價以及您對淨價的預期？或者我猜，今年的定價與去年相比如何？到目前為止，你們的簽約討論有什麼收穫嗎？謝謝。

Sure. Thanks, Ellie. Yeah. So what I'd say is in the US, we've given a range of $1 billion to $1.5 billion. And as I mentioned in my prepared remarks, we put in variability for competitive pressures, which gets into contracting and pricing, to your point, to your question, as well as vaccination rates. First on vaccination rates, if you look at the first half, as I mentioned, when we look at the spring booster, it was down roughly 10% or 11%.So that makes us feel good. It's a smaller sample size. But as we go into the second half, it's the only barometer we have heading into the second half.

當然。謝謝，艾莉。是的。所以我想說的是，在美國，我們給的金額範圍是 10 億到 15 億美元。正如我在準備好的演講中提到的那樣，我們考慮到了競爭壓力，這涉及到合約和定價的可變性，正如您所說，也涉及到您的問題，以及疫苗接種率。首先關於疫苗接種率，如果你看一下上半年的情況，正如我所提到的，當我們看春季加強劑時，疫苗接種率下降了大約 10% 或 11%。這讓我們感覺很好。樣本量較小。但當我們進入下半場時，這是我們進入下半場的唯一晴雨表。

As it pertains to pricing and contracting. Contracting is basically complete now. So we will look to the second half and pricing is also completed there. We're also looking at mNEXSPIKE in there as well. I would say just right now, all those factors are within the range, and we have confidence within that range. So I don't really want to be specific on pricing or our share at this point, but it's factored into our range, and we feel confident in it.

因為它涉及定價和簽約。目前承包工作已基本完成。因此，我們將展望下半年，定價也已完成。我們也正在研究其中的 mNEXSPIKE。我想說的是，目前所有這些因素都在範圍內，我們對這個範圍有信心。因此，我現在並不想具體談論定價或我們的份額，但它已計入我們的範圍，我們對此充滿信心。

Understood. Thanks.

明白了。謝謝。

Michael Yee, Jefferies.

傑富瑞 (Jefferies) 的麥可餘 (Michael Yee)。

Appreciate the opportunity for two questions. One is on CMV. I just wanted to follow up for Stephen. And maybe just talk to expectations about what you guys think is a positive readout, both on [VE], but also what is a good readout on the secondary endpoint that would help payers or patients or clinicians think about the value of CMV, given this novel type of vaccine for patients?

感謝有機會提出兩個問題。一個是關於CMV的。我只是想跟進史蒂芬的情況。也許只是談談你們對 [VE] 的積極讀數的期望，以及次要終點的良好讀數是什麼，這將有助於付款人或患者或臨床醫生思考 CMV 的價值，考慮到這種新型患者疫苗？

And then second, obviously, there has been various changes within FDA and CBER and within the ACIP, I just wanted to understand if you think that the dialogue remains very positive? And how are you expect things going forward? Thanks.

其次，顯然，FDA、CBER 和 ACIP 內部發生了各種變化，我只是想知道您是否認為對話仍然非常積極？您對未來發展有何期待？謝謝。

Great. Thank you, Michael, for both. So first, on the CMV results, we powered the study, and as we've said, we believe the product will have an impact if the vaccine efficacy in the primary endpoint is better than 49.1%. That was a lower bound acceptability threshold for the primary analysis against preventive infection. That's because you might say, well, 49% or 50% is that a substantial benefit. If you think of all of the burden of disease associated with CMV over a lifetime, a 50% reduction in that would be a pretty profound benefit, we believe, on public health and for individuals.

偉大的。謝謝你，麥可。首先，根據 CMV 結果，我們進行了這項研究，正如我們所說，我們相信，如果主要終點的疫苗有效性優於 49.1%，則該產品將產生影響。這是針對預防性感染進行初步分析的可接受性下限閾值。這是因為你可能會說，49% 或 50% 是一個實質的好處。如果您考慮到一生中與 CMV 相關的所有疾病負擔，我們相信，將其減少 50% 將對公共健康和個人產生相當大的好處。

There is complexity in terms of the individual indications because prevention of infection is one thing, but there's going to be a need to demonstrate value. Some of that will be demonstrated post approval with some of the real-world evidence generation studies. That always happen around vaccines. But we wanted to maximize the value we get of secondary endpoints in this study because we have such a rich study of information. And those include looking at things that you might think of as the persistence of virus in the blood or in the urine, the shedding and whether or not you were able to control that latent infection.

個別適應症具有複雜性，因為預防感染是一回事，但還需要證明其價值。其中一些將在批准後通過一些真實世界證據生成研究來證明。疫苗研發過程中總是會遇到這樣的情況。但我們希望最大限度地提高本研究中次要終點的價值，因為我們擁有如此豐富的研究資訊。這些包括觀察您可能想到的病毒在血液或尿液中的持續存在、脫落情況以及您是否能夠控制潛在感染。

I'll remind you that in their EBV vaccine Phase I study, which we shared previously a year ago. We were able to show quite strong impacts on the rates of virus, the presence of virus upon -- over time in patients that were EBV-positive who received our EBV vaccine, different program, but shows the level of control that we were excited to see in that program. If we saw something similar here in CMV, we think that would speak to the potential benefit about the risk of congenital transmission from, let's say, a pregnant mother who's becoming infected to her unborn child as well as other potential benefits related to the chronic issues, health issues that can come from CMV.

我要提醒您，在他們一年前我們分享過的 EBV 疫苗第一階段研究中。我們能夠證明，隨著時間的推移，接種我們的 EBV 疫苗的 EBV 陽性患者的病毒率、病毒的存在有相當大的影響，這是不同的計劃，但顯示了我們很高興在該計劃中看到的控制水平。如果我們在 CMV 中看到類似的情況，我們認為這將說明潛在的益處，即先天性傳播的風險，比如說，懷孕的母親被感染到她未出生的孩子，以及與 CMV 可能帶來的慢性問題、健康問題相關的其他潛在益處。

Obviously, for those, we don't have a prespecified hypothesis in the primary endpoint but we would love to see efficacy as good or better than what we're seeing in the primary of 49%. So 49% feels good for us, that's where we designed the study, and we are looking forward to it. Obviously, we hope to do better than that. But we will ultimately look to the totality of the data to understand the value of the product and given the burden of CMV in health systems and for individuals. We're quite hopeful that we'll be able to demonstrate that value quite quickly, including out of this Phase III study with the new secondary endpoints.

顯然，對於這些，我們在主要終點沒有預先指定的假設，但我們希望看到療效與我們在主要終點 49% 中看到的一樣好或更好。所以 49% 對我們來說感覺不錯，這就是我們設計這項研究的目的，我們對此充滿期待。顯然，我們希望做得更好。但我們最終將查看全部數據來了解產品的價值以及 CMV 對醫療系統和個人造成的負擔。我們非常希望能夠很快證明這一價值，包括這項具有新的次要終點的 III 期研究。

As it relates to the CBER changes and some of the ACIP changes, I'll just say that we continue to work closely with our review teams across all of our products. We are very grateful for the three approvals that happened in the last quarter. I will note that they happened on time, and that was through the, obviously, the incredibly diligent work of the folks at FDA to conduct those reviews in a rigorous way, and we continue to feel that those productive dialogues are going on now even on our existing files for the seasonal update.

由於它與 CBER 變化和一些 ACIP 變化有關，我只想說，我們將繼續與我們所有產品的審查團隊密切合作。我們非常感謝上個季度獲得的三項批准。我要指出的是，這些審查都是按時進行的，這顯然是透過 FDA 工作人員極其勤奮的工作，以嚴格的方式進行審查，我們繼續感到，即使在我們現有的季節性更新文件中，這些富有成效的對話仍在繼續。

We will always make sure that we provide prompt and fully transparent answers to the agency and work closely with them so that they can conduct that work and we're incredibly grateful for that. As well as CDC and ACIP, where we get questions that they need information on so that they can guide public health, we'll make sure that we provide that information. And we look forward to working with both CDC, ACIP, and FDA and CBER to continue to advance our pipeline and our mission.

我們將始終確保向該機構提供及時、完全透明的答复，並與他們密切合作，以便他們能夠開展這項工作，我們對此深表感謝。除了 CDC 和 ACIP，當我們收到他們需要資訊的問題以便他們能夠指導公共衛生時，我們會確保提供這些資訊。我們期待與 CDC、ACIP、FDA 和 CBER 合作，繼續推進我們的研發管線和使命。

Thank you.

謝謝。

Tyler Van Buren, TD Cowen.

泰勒範布倫 (Tyler Van Buren)，TD Cowen。

This is Greg on for Tyler. Do you have any early indications of what demand for COVID vaccines might look like this upcoming fall and winter season based on interactions with customers? Or will we need to wait to see early uptake at the end of this month or early next month? Thank you.

這是格雷格代替泰勒。根據與客戶的互動，您是否對即將到來的秋冬季 COVID 疫苗需求有任何早期跡象？或者我們需要等到本月底或下月初才能看到早期採用？謝謝。

Yeah. Look, I think first, let's separate outside the US versus inside the US part of that question, I think that that's probably more focused on the US. But outside the US many of our government customers are purchasing through advanced purchase agreements. And so those indications are pretty firm. You can see that in our even how we're guiding forward. And so some of those are under advanced purchase agreements. Others are under tenders that have been completed and published in those countries, and that feels quite stable.

是的。你看，我認為首先，讓我們把這個問題的美國境外部分與美國境內部分分開，我認為這可能更側重於美國。但在美國以外，我們的許多政府客戶都是透過預購協議進行採購的。所以這些跡像是相當肯定的。您甚至可以從我們的指引中看到我們是如何前進的。其中一些屬於預購協議。其他項目則在這些國家已經完成並公佈了招標，感覺相當穩定。

In the US, with customers, what I'd say is we saw a quite solid spring booster campaign. If you look from March 1 forward, the actual volumes in the spring booster campaign in the US were only slightly down from last year. And if you actually look at the 65-plus population, which is the core population, we think, going forward, given the new labels and framework for recommendation, it was actually down only 1% or 2% from March 1 to the end of the quarter, June 30, which I think speaks to the realization that those at high risk of severe COVID-19 continue to be compliant with public health recommendations and want to protect themselves even in the spring campaign.

在美國，對顧客來說，我想說的是，我們看到了一場相當紮實的春季促銷活動。如果從 3 月 1 日開始看，美國春季加強接種活動的實際接種量僅比去年略有下降。如果你實際上看一下 65 歲以上的人口（核心人口），我們認為，展望未來，考慮到新的標籤和建議框架，從 3 月 1 日到本季度末（6 月 30 日），這一數字實際上僅下降了 1% 或 2%，我認為這表明人們意識到，那些能保護嚴重 COVID-19 高風險的人會繼續在春季提出建議。

That has been the same experience, therefore, of our customers in the retail channel and elsewhere where they have seen that evidence in the last four months. And as we look to the fall, we obviously have some uncertainty, both about what the ultimate ACIP recommendation will be, as well as some of the other market uncertainties that exist. But we all want to be prepared to deliver a season that could be in line with prior seasons if the trends continue from the spring till now.

因此，這與我們的零售通路和其他地方的客戶在過去四個月中看到的這種證據是一樣的。展望秋季，我們顯然存在一些不確定性，包括 ACIP 最終的建議是什麼，以及其他一些存在的市場不確定性。但如果這種趨勢從春季一直延續到現在，我們都希望做好準備，迎接一個與前幾季保持一致的季節。

So we're going to remain cautiously optimistic. Certainly, our customers are preparing to make sure they have vaccines available if their customers and patients show up and the early signs are encouraging. But we need to be careful going into the fall. We think we really won't know until the end of the third quarter, until the end of September. As is always the case, for our seasonal business, which is we'll really get a clear picture in the first six weeks of the season as we launch.

因此我們將保持謹慎樂觀的態度。當然，我們的客戶正在準備確保如果他們的客戶和患者出現並且早期跡象令人鼓舞的話，他們有疫苗可用。但進入秋季後我們需要小心謹慎。我們認為，直到第三季末，也就是九月底，我們才會真正知道結果。對於我們的季節性業務，我們一如既往地會在推出業務後的前六週內真正了解情況。

Geoffrey Meacham, Citigroup.

花旗集團的傑弗瑞‧米查姆。

This is Charlie on for Geoff. Two real quick questions. You mentioned additional cost-cutting area that you could target. You noted that R&D is a primary driver of costs right now. How might you balance the need to bring later-stage infectious products market and also the need to shift away from seasonality factors that current products have?

這是查理 (Charlie) 代替傑夫 (Geoff)。兩個非常簡單的問題。您提到了可以針對的額外成本削減領域。您指出研發是目前成本的主要驅動因素。您如何平衡後期傳染病產品市場的需求以及擺脫當前產品季節性因素的需求？

And then second, on CMV, these secondary end points, the decision to add them, did they come on the back of interactions or discussions from FDA? Some color on that would be really helpful. Thank you.

其次，關於 CMV，這些次要終點，添加它們的決定是否基於與 FDA 的互動或討論？對此進行一些顏色標註確實會很有幫助。謝謝。

Sure. Yeah. Thanks, Charlie. So I think the first question was on how are we balancing our late-stage pipeline. I mean we still think we are investing quite a bit in our late-stage pipeline. So $3.6 billion to $3.8 billion is still significant, particularly, we are very conscious of where we are from a revenue standpoint. And we've made this decision and really stood by it for the last two years. We laid this out in 2023 that we were going to invest in our late-stage pipeline.

當然。是的。謝謝，查理。所以我認為第一個問題是我們如何平衡我們的後期管道。我的意思是，我們仍然認為我們在後期管道上投入了相當多的資金。因此，36 億美元到 38 億美元仍然是一筆不小的收入，特別是，我們非常清楚自己在收入方面的狀況。我們已經做出了這個決定，並且在過去的兩年裡一直堅持這個決定。我們在 2023 年就制定了計劃，將投資於我們的後期研發管線。

We continue to do that. We are actively adjusting as we go, and we will continue to adjust as we go. And that's why we're taking our cash costs from $9 billion down to $4 billion. But at the end of the day, you also mentioned seasonality. We think we are building a diversified portfolio that is not just seasonal. We do want to complete the respiratory portfolio that will be stronger when we have all the products together and give us more ability to compete.

我們將繼續這樣做。我們正在邊走邊調整，也會繼續邊走邊調整。這就是我們將現金成本從 90 億美元降至 40 億美元的原因。但最終，您也提到了季節性。我們認為我們正在建立一個不僅僅受季節性影響的多元化投資組合。我們確實希望完善呼吸產品組合，當我們將所有產品整合在一起時，該產品組合將更加強大，並賦予我們更強的競爭力。

But then when you look at CMV, our oncology pipeline and our rare disease pipeline, those aren't as seasonal. And so we believe that we are balancing both the need to complete the respiratory portfolio, invest in our late-stage pipeline, and invest in diversification in the company. And we've been doing that for the last two years, and we'll continue to do it, but we have had to adjust it down. So we did have greater ambitions, but we will continue to adjust and have adjusted, and I think that's what we're seeing.

但是當你查看 CMV、我們的腫瘤學管道和罕見疾病管道時，你會發現它們並不具有季節性。因此，我們相信，我們正在平衡完成呼吸產品組合、投資後期產品線以及投資公司多元化的需求。過去兩年我們一直這樣做，我們將繼續這樣做，但我們必須對其進行調整。因此，我們確實有更大的抱負，但我們會繼續調整，而且已經進行了調整，我認為這就是我們所看到的。

And maybe just to add to Jamey's point, we've also said that we will not invest in Phase III studies for new latent vaccine. So as you know, EBV, HSV vaccines, but we also say that we might be looking for partners, other project financing or pharma partners. And the Rare Disease, of course, small in terms of dollars. We also said we're going to focus on PA and MMA for now. We'll advance more programs later, but now we need to be financially disciplined.

也許只是為了補充 Jamey 的觀點，我們也說過，我們不會投資新潛伏疫苗的第三階段研究。如您所知，EBV、HSV 疫苗，但我們也說我們可能正在尋找合作夥伴、其他專案融資或製藥合作夥伴。當然，罕見疾病的治療費用從金額上來說很小。我們也說過我們現在將專注於 PA 和 MMA。我們稍後會推進更多項目，但現在我們需要嚴格財務紀律。

And in Oncology, as you know, for Intismeran, Merck is paying 50% of the cost, which is why, as Jamey explained, we have discussed this mechanical effect that is based on the strategy we decided to pursue to make sure that we drive back the company to profitability in 2018.

如您所知，在腫瘤學領域，對於 Intismeran，默克公司承擔了 50% 的費用，這就是為什麼正如 Jamey 所解釋的那樣，我們討論了這種機械效應，這種效應基於我們決定採取的策略，以確保我們能夠在 2018 年讓公司恢復盈利。

CMV question -- and on the CMV question, so just a little, again, sort of overall framing on this, we remain blinded to the primary results and the secondary results that are in the study. The interim analysis that we announced much earlier in this year was only on that primary endpoint, that's the design of those studies. But as we did not meet the criteria for early success in that interim analysis, we then proceed to the final, and the final has much more information in it.

CMV 問題—關於 CMV 問題，再一次，從總體上看，我們仍然無法了解研究中的主要結果和次要結果。我們今年稍早宣布的中期分析僅針對主要終點，這就是這些研究的設計。但由於我們在中期分析中沒有達到早期成功的標準，因此我們進入最終分析，最終分析中包含了更多資訊。

Obviously, we leave the primary endpoint unchanged, and we'll test against that. But if that is successful, there is an opportunity to pass down the alpha to powered secondary endpoints as well as there's a final opportunity for us to say, are we getting all the information we want from the blinded analysis prior to that unbinding event? And internally, at Moderna, we identified that there is -- we've actually been very successful in collecting data in the course of the study across a range of different potential endpoints. And we wanted to elevate some of those into that secondary endpoint analysis.

顯然，我們保持主要終點不變，並針對此進行測試。但如果成功了，我們就有機會將 alpha 傳遞到有動力的次要端點，同時也有最後一個機會讓我們說，在解除約束事件之前，我們是否從盲法分析中獲得了我們想要的所有資訊？在 Moderna 內部，我們發現——我們在研究過程中實際上非常成功地收集了一系列不同潛在終點的數據。我們希望將其中一些提升到次要終點分析。

In order to do that, while blinded, we have to then update the statistical analysis plan. We did consult with regulators as we are doing that. And we want to make sure that is done in the utmost to a gold standard, high-integrity way prior to conducting the analysis that we can get the full benefit of that additional information that is in the study. So again, we remain blinded. This is just a diligence matter of making sure we get this updated in the right way, and then we'll look forward to proceeding forward with that analysis.

為了做到這一點，在盲測的情況下，我們必須更新統計分析計畫。我們在這樣做的時候確實諮詢了監管機構。我們希望確保在進行分析之前以黃金標準、高完整性的方式盡最大努力完成這項工作，以便我們能夠充分利用研究中的附加資訊。所以我們又陷入了盲點。這只是一個盡職調查問題，確保我們以正確的方式進行更新，然後我們期待繼續進行該分析。

And we have done that in consultation, obviously with regulators, but we initiated that ourselves. Last point, I just can underscore, we will still expect this in 2025. At this point, we have the data in hand. It is literally just making sure we dot our Is and cross our Ts before conducting that analysis this fall.

我們已經與監管機構進行了磋商，但這是我們自己發起的。最後一點，我只想強調，我們仍然期待 2025 年實現這一點。此時，我們已經掌握了數據。這實際上只是確保我們在今年秋天進行分析之前把一切都做好。

Courtney Breen, Bernstein.

考特尼·布林，伯恩斯坦。

A couple of pieces that I wanted to just touch on. First, with the INT, it looks like you've added the first-line melanoma in there. How do you think about kind of patients being treated over the course of their disease. You're already kind of hitting them in the early stages of the adjuvant space and now popping up with a new first-line trial for the metastatic space. Could you imagine a world where patients might get kind of an INT twice in the course of their disease state if they were to progress? Or will this be a more narrow patient population in the first line, those that perhaps haven't had it in an earlier stage.

我想簡單談談其中的幾點。首先，透過 INT，看起來您已經在其中添加了一線黑色素瘤。您如何看待患者在患病過程中所接受的治療？您已經在輔助治療領域的早期階段對他們進行了打擊，現在又開始了針對轉移性治療領域的新的一線試驗。您能想像這樣一個世界嗎：如果病患病情惡化，他們可能會在病情發展過程中接受兩次 INT？或者這將是一線中較狹窄的患者群體，那些可能在早期沒有患過這種疾病的人。

The second question that I did want to ask was just in terms of the kind of employee headcount cost cutting that you have just announced. Can you just add some more context, and apologies if I've missed this, on kind of where you are focused with kind of removing some of that headcount? Are there any places that you're adding to kind of enhance efficiencies? And so just talking about kind of what the ins and outs might look like to get to that new employee headcount. Thank you.

我想問的第二個問題是關於您剛剛宣布的員工人數成本削減措施。您能否補充一些背景信息，如果我遺漏了這一點，請見諒，關於您在裁減部分員工方面將重點放在哪些方面？您是否要添加某些地方來提高效率？所以只是談談增加新員工人數的具體細節。謝謝。

Thank you. I'll take the INT question first. So as you mentioned, we are looking at first-line metastatic melanoma. We look forward to a day when melanoma patients broadly are getting INTs early in the adjuvant setting. But right now, the reality is as we're not yet approved and being used in that space, there's still a substantial need in frontline metastatic. Your question was sort of could we expect a world maybe in that distant future where we are being used in both places. And I think the answer is yes.

謝謝。我先回答 INT 問題。正如您所說，我們正在研究一線轉移性黑色素瘤。我們期待有一天黑色素瘤患者能夠在早期輔助治療中廣泛接受 INT 治療。但目前，現實情況是，由於我們尚未獲得批准並用於該領域，因此在前線轉移性治療方面仍然存在巨大的需求。你的問題是，我們是否可以期待在遙遠的未來，我們在兩個地方都被利用。我認為答案是肯定的。

I'll remind you, it's an individualized treatment, an individualized treatment we make on a biopsy of your tumor at the time of when it happens. So it's conceivable that you could get a durable benefit in the adjuvant setting and maybe very much more distantly have a metastatic event. And the neoantigens in your tumor might have changed. So the actual INT you would get in that frontline setting would actually be updated for the evolution of your own personal cancer.

我要提醒你，這是一種個人化治療，我們會根據你的腫瘤發生時的活檢情況進行個別化治療。因此，可以想像，您可以在輔助治療中獲得持久的益處，並且可能更遙遠地發生轉移事件。而你的腫瘤中的新抗原可能已經改變了。因此，您在前線環境中獲得的實際 INT 實際上會根據您自身癌症的發展進行更新。

And that would be a world where you can obviously see the potential for treating early and treating late. That's speculative in the sense that it's far out there, and we'll have to prove those things. But certainly, we could see a world where people are receiving different versions of their individualized neoantigens therapy throughout the treatment of their cancer.

在那個世界裡，你可以清楚地看到早期治療和晚期治療的潛力。這只是推測，因為它還很遙遠，我們必須證明這些事情。但可以肯定的是，我們可以看到，在癌症治療過程中，人們會接受不同版本的個人化新抗原治療。

And I'll take the second question on employees, Courtney. If you look at it, basically, there's a few buckets, clearly the manufacturing driven by productivity, whether it's technology productivity or processes or other things we are doing. In R&D, as we talked about a lot -- and again, this is part of our strategy. We are not investing in new Phase III study in respiratory. So as those phase out, of course, there are some capacity that we need to kind of resize as you can imagine, and we're not starting new ones.

我將回答有關員工的第二個問題，考特尼。如果你看一下，基本上，有幾個桶，顯然是由生產力驅動的製造業，無論是技術生產力還是流程或我們正在做的其他事情。在研發方面，正如我們討論過的許多內容——這也是我們策略的一部分。我們沒有投資呼吸系統疾病的新的 III 期研究。因此，隨著這些產能的逐步淘汰，當然，正如您所想像的，我們需要對一些產能進行調整，而且我們不會啟動新的產能。

We're not starting later on Phase III. And then G&A is a lot of productivity across the board. So we'll, of course, continue to hire, I think if you check, check, I think a week ago, there's still like 150 position on Moderna's website right now. We are hiring as we need to grow the business, to prepare the launches. So of course, this is very important.

我們不會稍後再開始第三階段。然後，G&A 在各個方面都具有很大的生產力。因此，我們當然會繼續招聘，我想如果你檢查一下，我想一周前，Moderna 的網站上現在仍然有 150 個職位。我們正在招募人才，以滿足業務成長和產品發布的需要。所以這當然非常重要。

Cory Kasimov, Evercore ISI.

Cory Kasimov，Evercore ISI。

This is [Adi] on for Cory. I wanted to ask a little more on the decision to start the first-line metastatic melanoma trial for Intismeran. What does this suggest about what you're learning about the product, where it might be best suited to work and your evolving confidence in the program?

這是 [Adi] 為 Cory 上場。我想進一步詢問有關啟動 Intismeran 一線轉移性黑色素瘤試驗的決定。這顯示您對該產品有何了解？該產品最適合用於什麼地方？您對該產品的信心不斷增強嗎？

Thank you for the question. Look, we continue to follow the randomized Phase IIb results from our adjuvant melanoma study. And I think as we have seen in the repeated updates, and we hope to provide a future updates on that, as I mentioned previously, we continue to have enthusiasm from that study. And that really lays the foundation for why we are optimistic about the overall program.

謝謝你的提問。你看，我們繼續關注輔助黑色素瘤研究的隨機 IIb 期結果。我認為，正如我們在反覆更新中看到的那樣，我們希望提供未來的更新，正如我之前提到的，我們繼續對這項研究充滿熱情。這確實為我們對整個計劃持樂觀態度奠定了基礎。

If you look across where we have made with our partner, Merck, the most sizable investments, we have obviously been looking most substantially in the adjuvant settings. And that makes sense to us where the burden of the tumor is the lowest and where your immune system has the greatest chance of achieving a really significant response. And so I don't want to lose sight of the fact that we still believe adjuvant settings are important.

如果您回顧我們與合作夥伴默克公司進行的最大規模投資，您會發現我們顯然在輔助治療領域投入了最多的資金。這對我們來說是有意義的，因為腫瘤負擔最輕，免疫系統最有可能產生真正顯著的反應。因此我不想忽視我們仍然相信輔助治療很重要這一事實。

I'll also note that we've gone for some monotherapy smaller studies that we're starting to look at, which have us looking even earlier than adjuvant in some ways. And so we're quite enthusiastic about the program potential from adjuvant and earlier.

我還要指出的是，我們已經開始進行一些單一療法的小型研究，在某些方面，這些研究甚至比輔助療法更早。因此，我們對該計劃在輔助治療和早期治療方面的潛力非常感興趣。

That said, we also want to assess diligently whether or not there's an opportunity for us to do late stage, particularly in the metastatic indication. And that's where metastatic melanoma made the most sense. It was also enabled by some progress we've really made on the manufacturing side.

也就是說，我們也想認真評估是否有機會進行後期治療，特別是在轉移性適應症方面。這就是轉移性黑色素瘤最有意義的地方。這也得益於我們在製造方面取得的一些進展。

Now I will just make a last comment on the metastatic indication is that those are patients that if they're unfortunately at that stage, they tend to progress quite quickly. And we need to be sure that we can deliver highly efficiently, highly reliably a product for them inside of six weeks or hopefully even better from a quick turnaround perspective so that they can start being treated by the drug post enrollment in the study.

現在，我只想對轉移性指徵做最後的評論，那就是如果這些患者不幸處於那個階段，他們的病情往往會進展得相當快。我們需要確保能夠在六週內為他們提供高效、高可靠的產品，或從快速週轉的角度來看甚至更好，以便他們可以在研究後開始接受藥物治療。

And so it's quite pragmatic to say, let's build up the capability in the adjuvant and early space, but then now go in a targeted way and look in later stage. And what we've really seen in the Intismeran clinical portfolio, over now, many studies and over 1,000 patients treated is this opportunity for us to look in the late stage with a rapid turnaround and highly efficient manufacturing system.

因此，我們可以務實地說，讓我們先在輔助和早期領域建立能力，然後再有針對性地進行後期研究。目前，我們在 Intismeran 臨床組合中看到的是，許多研究和超過 1,000 名患者的治療為我們提供了一個機會，讓我們能夠透過快速週轉和高效的製造系統來展望後期發展。

But I don't want to lose sight of the fact that we still really believe in the adjuvant space, that is the major place that we're betting, but we do believe that earlier than adjuvant and perhaps in the front line are worth looking at as well, and we'll be doing that in the studies that we just announced.

但我不想忽視這樣一個事實，即我們仍然非常相信輔助治療領域，這是我們押注的主要領域，但我們確實相信，比輔助治療更早的治療，甚至可能在前線的治療也值得關注，我們將在剛剛宣布的研究中這樣做。

Got it. And then just a follow-up, can you discuss any regulatory interactions you have had on the path ahead for Checkpoint AIM-T? I see on Slide 12, that is now expected to be filed for approval by 2028? Thank you.

知道了。然後只是一個後續問題，您能否討論一下在 Checkpoint AIM-T 未來的發展道路上所遇到的任何監管互動？我在第 12 張投影片上看到，預計到 2028 年才會提交批准？謝謝。

Thank you for that question. So 4359, we have been engaging with regulators. Those are early stage. I won't get into the specifics of them. I'll remind you, we're just now moving into Phase II. And so these are really Phase I stage conversations, which would make it premature to go too much into specifics. That said, we are investing behind the program.

謝謝你的提問。因此 4359，我們一直在與監管機構合作。這些都是早期階段。我不會深入討論它們的具體細節。我提醒你，我們現在才剛進入第二階段。因此，這些實際上還處於第一階段的對話中，現在討論太多細節還為時過早。也就是說，我們正在對該計劃進行投資。

And as we announced at the last quarter, we're investing as though this could become one of our submissions over the next three years, as you identified sort of by 2028, that really is a statement about our prioritization of the program and our conviction given the very early stage data and not necessarily a statement about anything we've done either out of Phase II and subsequent discussions with regulators about approval time line. So it's our prioritization of the program that brings that forward. But we believe it is possible.

正如我們在上個季度宣布的那樣，我們正在進行投資，就好像這可能會成為我們未來三年提交的項目之一，正如您所說，到 2028 年，這實際上是關於我們對該計劃的優先考慮以及我們對非常早期數據的信心的聲明，而不一定是關於我們在第二階段以及隨後與監管機構討論批准時間表方面所做的任何事情的聲明。因此，我們對該計劃的優先排序促使了這一進程。但我們相信這是可能的。

Luca Issi, RBC.

盧卡·伊西（Luca Issi），RBC。

Maybe one, Stephane, bigger picture, can you maybe just talk about business development here? We've obviously seen a lot of assets being in-license from China, including obviously, one of your competitors that actually licensed the assets and even flipped it to pharma for some means of profits. Given your long-term ambition to become a key player in oncology, are you actively spending time in China, and if so, are you just looking at strengthening your mRNA capabilities? Or are you open to other modalities?

也許首先，史蒂芬，從更大的角度來看，您是否在這裡能談談業務發展？我們顯然已經看到很多資產從中國獲得許可，其中顯然包括你們的某個競爭對手，他們實際上獲得了資產許可，甚至將其轉賣給製藥公司以獲取某種利潤。鑑於您長期致力於成為腫瘤學領域的重要參與者，您是否積極在中國投入時間？如果是，您是否只是想加強您的 mRNA 能力？或者您是否願意接受其他方式？

And then maybe second, Stephen, can you just talk about the COVID plus flu how should we think about the sequence of the filing here with the FDA? Is it fair for us to think that you first need to get approved for flu monotherapy and then you can file the combo, or can you possibly do both concurrently? I guess any color there, much appreciated so we can think about timelines. Thanks so much.

然後也許第二個問題，史蒂芬，您能否談談 COVID 和流感，我們應該如何考慮向 FDA 提交申請的順序？我們是否可以認為，您首先需要獲得流感單一療法的批准，然後才能提交組合療法的申請，或者您可以同時進行這兩項治療？我想那裡有任何顏色，非常感謝，這樣我們就可以考慮時間表。非常感謝。

So on the first question, as we've said before, we have such a productive platform in mRNA that we have an abundance of assets. Actually, what we are doing, as you heard on the cost structure, we are deciding not to take forward to Phase III asset that we believe deeply into, take EBV, for example, because we ought to be financially disciplined. But we've said we believe this vaccine is really important for patients. As you know, we have two program in EBV. There is a prophylactic program to prevent mononucleosis and potentially long-term sequelae of MS and there's a potential therapeutic program for people that are already sick.

因此，關於第一個問題，正如我們之前所說，我們在 mRNA 領域擁有如此高效的平台，以至於我們擁有豐富的資產。實際上，正如您在成本結構中聽到的那樣，我們正在做的事情是，我們決定不推進我們深信不疑的第三階段資產，例如 EBV，因為我們應該遵守財務紀律。但我們說過，我們相信這種疫苗對病人確實很重要。如您所知，我們在 EBV 中有兩個項目。有一個預防計劃可以預防單核細胞增多症和多發性硬化症的潛在長期後遺症，並且有一個針對已經患病的人的潛在治療計劃。

And we believe those programs have to move forward, which is why, as we've said on previous calls, we are actively talking to potential pharmaceutical partner and potential product financing partners for several of those assets that we cannot prosecute forward alone because they are great assets, but we need to be financially disciplined at the same time.

我們相信這些項目必須繼續推進，這就是為什麼，正如我們在先前的電話會議上所說的那樣，我們正在積極與潛在的製藥合作夥伴和潛在的產品融資合作夥伴就其中幾項資產進行談判，我們不能單獨推進這些資產，因為它們是寶貴的資產，但同時我們需要在財務上保持紀律。

We've always thought that partnering is a great way to access assets that are non-mRNA technology. I mean, a good example, of course, is our important strategic partnership with Merck with KEYTRUDA. We could have decided to develop our own PD-1, everybody don't think this was the right thing to do.

我們一直認為合作是獲取非 mRNA 技術資產的絕佳方式。我的意思是，一個很好的例子當然是我們與默克在 KEYTRUDA 上建立的重要策略夥伴關係。我們本來可以決定要開發自己的 PD-1，但每個人都認為這不是正確的做法。

But partnering with Merck in term of having an approved product and the right capabilities was. So we're always going to look at the biology. That's what has always driven us to try to find the best way to help patients and to create the best asset. And if we need a partnership, we will do so.

但就獲得批准的產品和適當的能力而言，與默克合作是可行的。因此我們總是會關註生物學。這始終激勵著我們努力尋找最佳方式來幫助患者並創造最佳資產。如果我們需要合作，我們就會這樣做。

And thanks for the question on the COVID-flu combo. So look, I'll first say, concurrent is certainly possible. You're asking whether it's theoretically possible. I think we think it is. But as a practical matter, there will probably be some sequencing. And as a practical matter in the case of the US FDA, it's likely that the flu vaccine will be sequenced first for all of the reasons that are obvious. It's that a chance to review that efficacy data from that flu vaccine feels very important for ungating the flu-COVID combination.

感謝您提出有關 COVID-流感組合的問題。所以，我首先要說的是，並發當然是可能的。您問的是理論上是否可行。我認為我們是這麼認為的。但從實際情況來看，可能會有一些先後順序。從美國 FDA 的實際情況來看，出於顯而易見的原因，流感疫苗很可能會先被排序。審查流感疫苗的有效性數據的機會對於解除流感-新冠組合的限制非常重要。

Now the one caveat I'd put on that is there are markets where we continue to proceed with our flu-COVID vaccine application, including in Europe, where we have -- we believe we're going to be able to amend that file to include the flu efficacy data.

現在我要提出的一個警告是，在某些市場，我們將繼續推進流感 COVID 疫苗的申請，包括在歐洲，我們相信我們將能夠修改該文件以包括流感功效數據。

And so the answer is ultimately dependent on the different regulators in different markets. It is possible that we could proceed in parallel but for pragmatic reasons, we may proceed in sequence. And so that doesn't mean that we're delaying for 1 to be approved before we submit, but we are allowing substantially through to proceed before proceeding with the flu-COVID, again, market to market, different answers.

因此，答案最終取決於不同市場的不同監管機構。我們有可能同時進行，但出於務實的原因，我們可能會按順序進行。因此，這並不意味著我們會推遲等待 1 獲得批准後再提交，而是我們會在繼續處理流感 COVID 之前允許實質性的推進，同樣，每個市場都有不同的答案。

Thank you so much.

太感謝了。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

I have two, maybe just follow flu-COVID comments here or discussion here. So any latest thoughts regarding flu combo submission requirement? This is specifically regarding the FDA. And then second, regarding the CMV, how do you decide the statistical hierarchy for the secondary endpoint? And also given the study basically already completed, is it fair to say in two months, we will see the data?

我有兩個，也許只是關注這裡的流感-COVID 評論或這裡的討論。那麼，關於流感組合提交要求有什麼最新想法嗎？這是專門針對 FDA 的。其次，關於 CMV，您如何確定次要終點的統計層次？而且鑑於研究基本上已經完成，是否可以說兩個月後我們就能看到數據？

That's very specific questions. Thank you, Gena, for all of them. So on the flu-COVID, we're actually beginning those consultations with the FDA. And so we'll wait for a week for us to have guidance from them on what their requirements are. But the previous review, it was clear that we needed to submit the flu efficacy results and confirm the correlative protection from that study that we now have.

這是非常具體的問題。感謝吉娜 (Gena) 所做的一切。因此，關於流感-COVID，我們實際上已經開始與 FDA 進行磋商。因此，我們將等待一周時間，以獲得他們的指導，以了解他們的要求是什麼。但先前的審查明確指出，我們需要提交流感療效結果，並確認我們現在擁有的該研究的相關保護。

And so we will go back and confirm that that is necessary, as well as understand any other information the FDA would want to see in the application. When we've had that consultation, we'll be able to provide more clarity. I don't have that now.

因此，我們將回過頭來確認這是否必要，並了解 FDA 希望在申請中看到的任何其他資訊。當我們進行完諮詢後，我們將能夠提供更清晰的答案。我現在沒有那個。

As far as CMV in terms of the hierarchy. We have not yet disclosed what the powered secondary endpoint will be or some of the other things that we are looking at. We will, once we are obviously unblinding the study, but the -- what we're looking to do is a hierarchical testing, as you can imagine, that we're passing the alpha down to that secondary. And then we're also making sure that we characterize all the additional secondary endpoints that we think will be useful in terms of characterizing the performance of the vaccine on a number of different immunologic and virologic measures.

就 CMV 的層次結構而言。我們尚未透露供電次級端點是什麼，或者我們正在研究的其他一些事情。一旦我們揭開研究的神秘面紗，我們就會這麼做，但是 — — 我們希望進行的是分層測試，正如你所想像的，我們會將 alpha 傳遞給二級測試。然後，我們還要確保描述我們認為在表徵疫苗在許多不同免疫學和病毒學指標上的性能方面有用的所有其他次要終點。

Last question, when will we see the data? We have completed the study. We are going to be diligent and careful in dotting our Is and crossing the Ts. We have not completed the analysis. And so will we have most of the data? I would say that we are completely blinded to those results.

最後一個問題，我們什麼時候才能看到數據？我們已經完成了這項研究。我們將勤勉、謹慎地做好每一件事。我們尚未完成分析。那我們會獲得大部分數據嗎？我想說，我們對這些結果完全視而不見。

And so it will take some time to first make sure that we have all the appropriate approvals on the update to the statistical analysis plan, everywhere we want. And then we will initiate the analysis, and there will be some period of time for an unblinded statistical team to conduct all the correct analysis and review that DSMB and then will be informed. We do expect that to happen this fall. I will not say whether or not we expect it to happen within the next two months because honestly, I don't exactly know today how much time it takes to go through those approvals and complete those analysis, but we're quite confident that it will happen probably.

因此，我們需要花一些時間來首先確保對統計分析計劃的更新獲得所有適當的批准，包括我們想要的所有內容。然後我們將啟動分析，並留出一段時間讓非盲統計團隊進行所有正確的分析和審查，然後 DSMB 會收到通知。我們確實希望這將在今年秋天發生。我不會說我們是否預計它會在未來兩個月內發生，因為老實說，我今天並不確切知道通過這些批准和完成這些分析需要多長時間，但我們非常有信心它可能會發生。

Thank you.

謝謝。

Ladies and gentlemen, that concludes the Q&A portion of today's conference. I'd like to turn the call back over to Stephane for any closing remarks.

女士們、先生們，今天會議的問答部分到此結束。我想將電話轉回給史蒂芬，請他做最後發言。

Well, thank you, everybody, for joining us today. We really appreciate it. We look forward to speaking to you in the next days or weeks. Have a nice day and a good weekend. Thanks.

好吧，謝謝大家今天加入我們。我們非常感激。我們期待在接下來的幾天或幾週內與您交談。祝您有個愉快的一天和週末。謝謝。

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

女士們、先生們，今天的演講到此結束。現在您可以斷開連接，享受美好的一天。