莫德納 (MRNA) 2024 Q4 法說會逐字稿

Good day, and thank you for standing by.

您好，感謝您的支持。

Welcome to the Moderna fourth quarter 2024 conference call.

歡迎參加 Moderna 2024 年第四季電話會議。

(Operator Instructions) Please be advised, today's conference is being recorded.

（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.

現在，我想將會議交給今天的發言人拉維娜·塔盧克達 (Lavina Talukdar)。

Please go ahead.

請繼續。

Thank you, Kevin.

謝謝你，凱文。

Good morning, everyone, and thank you for joining today's call to discuss Moderna's fourth quarter and full year 2024 financial results And business updates.

大家早安，感謝您參加今天的電話會議，討論 Moderna 2024 年第四季度和全年財務業績和業務更新。

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.

您可以造訪我們網站的投資者部分，查看今天早上發布的新聞稿以及我們將要審查的幻燈片。

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

參加今天電話會議的有執行長 Stéphane Bancel； Jamey Mock，財務長；以及總裁 Stephen Hoge。

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

在我們開始之前，請注意，本次電話會議將包括根據 1995 年私人證券訴訟改革法的安全港條款做出的前瞻性陳述。

Please see slide twoof the accompanying presentation and our SEC filings for important risk factors that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements.

請參閱隨附簡報的第二張投影片和我們向美國證券交易委員會提交的文件，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表達或暗示的業績和結果存在重大差異的重要風險因素。

I will now turn the call over to Stephane.

現在我將電話轉給史蒂芬 (Stephane)。

Thank you, Lavina.

謝謝你，拉維娜。

Good morning or good afternoon, everyone.

大家早安或下午好。

Thank you for joining us.

感謝您加入我們。

I will start with a review of 2024.

我將從 2024 年的回顧開始。

Jamey will present our financial results and outlook.

Jamey 將介紹我們的財務表現和展望。

Stephen will review our clinical programs.

史蒂芬將審查我們的臨床項目。

I will then come back and show our key priorities for 2025 before we take your questions.

在回答你們的問題之前，我會回來介紹我們 2025 年的重點優先事項。

In 2024, we recorded revenue of $3.2 billion.

2024年，我們的收入達到 32 億美元。

The team has looked how to generate cost savings of $2.6 billion or 27% down from 2023.

該團隊一直在研究如何節省 26 億美元（比 2023 年下降 27%）的成本。

We reported a loss of $3.6 billion.

我們報告的損失是 36 億美元。

While we have anticipated to end the year with $9 billion in cash, thanks to the team's work on OpEx, CapEx and also working capital, we ended the year with $9.5 billion of cash and investments at year-end.

雖然我們預計今年年底的現金餘額為 90 億美元，但由於團隊在營運支出、資本支出以及營運資金方面所做的工作，我們在年底的現金和投資餘額為 95 億美元。

In September 2024, we announced our focus on 10 high-value programs for which we expect financial approvals over the next three years, driving sales growth and diversification from our top line from COVID.

2024 年 9 月，我們宣布將重點關注 10 個高價值項目，預計這些項目將在未來三年內獲得財務批准，從而推動銷售成長和 COVID 帶來的營收多元化。

This program includes the respiratory vaccine, next-gen COVID, combination of flu plus COVID, RSV 18 to 59 at five-week, flu.

該計劃包括呼吸道疫苗、下一代 COVID、流感加 COVID 的混合疫苗、五週的 RSV 18 至 59 疫苗、流感。

In late, CMV and Norovirus.

晚期，CMV和諾羅病毒。

In rare disease, PA and MMA.

在罕見疾病中，PA 和 MMA。

And oncology, INT for adjuvant melanoma.

以及腫瘤學、輔助黑色素瘤的 INT。

In addition to pulling sales growth, the prioritization of these programs will allow us to reduce our R&D expenses in this time frame.

除了拉動銷售成長之外，這些項目的優先實施還能讓我們在這一時間範圍內減少研發費用。

From a pipeline standpoint, it was a year of strong progress.

從管道角度來看，這是取得長足進步的一年。

In 2024, we became a multiproduct company who we have power of

2024 年，我們成為一家擁有強大

.

。

Along with buybacks, we now have two commercial products on the market.

除了回購之外，我們現在還有兩款商業產品推出市場。

We reported positive Phase III results in four of our program, and we filed for FDA approval on next-gen COVID, our combination of flu plus COVID and the RSV vaccine for RSV 18 to 59.

我們報告了四個項目的 III 期積極結果，並向 FDA 申請批准下一代 COVID，這是我們針對 RSV 18 至 59 的流感加 COVID 和 RSV 疫苗的組合。

And vaccine is currently in a Phase III efficacy trial.

目前疫苗正處於第三階段效力試驗。

We also reported additional progress across our programs for the Phase I/II from vaccine against Norovirus, EBV and BBB.

我們也報告了針對諾羅病毒、EBV 和 BBB 疫苗的 I/II 期計畫的更多進展。

In oncology, we presented data at major medical meetings in 2024.

在腫瘤學領域，我們在 2024 年的主要醫學會議上展示了數據。

For INT program, in June, we reported positive data in adjuvant melanoma for the Phase II trial.

對於 INT 計劃，我們在六月報告了第二階段輔助黑色素瘤試驗的積極數據。

In addition, for checkpoint program vaccine, mRNA-4359, we presented positive Phase I data in September.

此外，對於檢查點計劃疫苗mRNA-4359，我們在9月份公佈了積極的I期數據。

In [rare disease], we had positive early safety and clinical data from PA and MMA.

在[罕見疾病]中，我們從 PA 和 MMA 獲得了積極的早期安全性和臨床數據。

With that, I will hand over to Jamey.

說完這些，我將把權交給 Jamey。

Thanks, Stephane, and hello, everyone.

謝謝，史蒂芬，大家好。

Today, I will walk through our financial results for the fourth quarter and full year 2024, providing insights into the key drivers behind our performance.

今天，我將介紹我們 2024 年第四季和全年的財務業績，並深入了解我們業績背後的關鍵驅動因素。

I'll also outline our 2025 financial framework as we continue to optimize our operations and position the company for long-term success.

我還將概述我們的 2025 年財務框架，因為我們將繼續優化營運並為公司的長期成功做好準備。

Let's begin by reviewing our commercial performance on slide 8.

讓我們先回顧一下第 8 張投影片上的商業表現。

For the fourth quarter of 2024, net product sales were $0.9 billion, with $0.2 billion in the United States and $0.7 billion outside the United States.

2024 年第四季，淨產品銷售額為 9 億美元，其中美國境內 2 億美元，美國境外 7 億美元。

For the full year, net product sales were $3.1 billion, at the lower end of our revised guidance.

全年淨產品銷售額為 31 億美元，處於我們修訂後的預期低端。

US sales were $1.7 billion for the year, benefiting from a $0.2 million favorable adjustment related to a prior period return reserve reversal.

美國全年銷售額為 17 億美元，受益於與前期退貨準備金沖銷相關的 20 萬美元有利調整。

Excluding this adjustment, sales volume saw a decline compared to last year, primarily due to lower vaccination rates, lower market share and increased competition.

不計入此項調整，銷售量較去年同期下降，主要原因是疫苗接種率下降、市佔率下降、競爭加劇。

However, we observed signs of stabilization and believe the COVID market will remain durable over time.

然而，我們觀察到了穩定的跡象，並相信 COVID 市場將隨著時間的推移保持持久。

Outside the US, product sales were $1.4 billion, aligning with the midpoint of our guidance.

在美國以外，產品銷售額為 14 億美元，與我們的預期中位數一致。

This includes approximately $400 million from advanced purchase agreements that will not recur in 2025.

其中包括約 4 億美元的預購協議，這些協議在 2025 年不會重複出現。

The vast majority of our sales were from Spikevax.

我們絕大部分的銷售量都來自Spikevax。

While we launched our second product, mRESVIA, in the third quarter, sales were only $25 million for the full year.

雖然我們在第三季推出了第二款產品 mRESVIA，但全年銷售額僅為 2,500 萬美元。

While early RSV sales were limited, we see long-term opportunity to expand our presence in this market, both in the US and internationally.

雖然早期 RSV 銷售有限，但我們看到了擴大我們在美國和國際市場上影響力的長期機會。

Moving on to slide 9.

轉到第 9 張投影片。

I will now walk through our financial results for the fourth quarter of 2024.

現在我將介紹我們 2024 年第四季的財務表現。

Total revenue for the fourth quarter was $966 million, down 66% from the same period last year.

第四季總營收為9.66億美元，較去年同期下降66%。

As expected, sales were impacted by the earlier launch of our updated COVID vaccine in the US, with FDA approval granted three weeks earlier than the prior year.

正如預期，銷售額受到我們更新的 COVID 疫苗在美國提前推出的影響，FDA 批准比去年提前了三週。

This allowed us to meet demand sooner, shifting a portion of sales into the third quarter.

這使我們能夠更快地滿足需求，將部分銷售轉移到第三季。

International sales were also lower year-over-year, reflecting the ongoing phaseout of advanced purchase agreements.

國際銷售額也較去年同期下降，反映出預購協議的逐步取消。

Cost of sales for the quarter was $739 million, including $45 million in third-party royalties, $193 million in inventory write-downs and a noncash charge of $238 million from the termination of a contract manufacturing agreement.

本季銷售成本為 7.39 億美元，其中包括 4,500 萬美元的第三方特許權使用費、1.93 億美元的庫存減記以及因終止合約製造協議而產生的 2.38 億美元的非現金費用。

The contract termination is part of our continued effort to optimize our manufacturing footprint, following the strategic resizing initiative launched in 2023 to align with the transition to a seasonal endemic market.

繼 2023 年啟動策略調整計畫以適應向季節性地方性市場的過渡之後，終止合約是我們持續努力優化製造足跡的一部分。

While cost of sales declined by $190 million compared to the prior year, lower product sales volume drove cost of sales to 79% of product sales.

雖然銷售成本與前一年相比下降了 1.9 億美元，但產品銷售量下降導致銷售成本佔產品銷售額的 79%。

Excluding the resizing charge, this would have been 53%.

如果不計調整大小的費用，這個比例將是 53%。

R&D expenses in Q4 were $1.1 billion, reflecting a 20% year-over-year decline.

第四季研發費用為 11 億美元，較去年同期下降 20%。

The decrease was primarily driven by lower clinical development and manufacturing costs across our COVID, RSV, flu and combination vaccine programs.

下降的主要原因是我們的 COVID、RSV、流感和聯合疫苗項目的臨床開發和製造成本降低。

This was partially offset by increased investments in our Norovirus and INT programs.

這在一定程度上被我們對諾羅病毒和 INT 項目的增加的投資所抵消。

Additionally, last year's R&D expenses included $120 million upfront payment related to our collaboration with [Thematics], which did not recur this year.

此外，去年的研發費用包括與 [Thematics] 合作相關的 1.2 億美元預付款，這筆費用今年沒有再次發生。

SG&A expenses for the fourth quarter were $351 million, down 25% year-over-year.

第四季銷售、一般及行政開支為 3.51 億美元，較去年同期下降 25%。

The decrease was primarily driven by reductions in purchased services and external consultants as we continue to focus on cost management and operational efficiencies.

由於我們繼續注重成本管理和營運效率，導致購買服務和外部顧問的減少。

We recognized an income tax benefit of $64 million in the fourth quarter.

我們在第四季度確認了 6,400 萬美元的所得稅收益。

Similar to the prior year, the benefit was not material, due to the global valuation allowance maintained against most of our deferred tax assets.

與前一年類似，由於我們對大多數遞延稅務資產保留了全球估值準備金，因此收益並不重大。

Net loss for the quarter was $1.1 billion compared to net income of $217 million in Q4 2023.

本季淨虧損為 11 億美元，而 2023 年第四季淨收入為 2.17 億美元。

Loss per share was $2.91 compared to earnings per share of $0.55 in the prior period.

每股虧損為 2.91 美元，而上一期間每股收益為 0.55 美元。

We ended the quarter with cash, cash equivalents and investments totaling $9.5 billion, up from $9.2 billion at the end of the third quarter.

本季末，我們的現金、現金等價物和投資總額為 95 億美元，高於第三季末的 92 億美元。

The increase was primarily due to accounts receivable collections.

成長的主要原因是應收帳款收回。

Now let's turn to our full year 2024 financial results on slide 10.

現在讓我們來看看第 10 張投影片上的 2024 年全年財務表現。

Total revenue for the year was $3.2 billion, a 53% decline from 2023, primarily driven by lower product sales, which I discussed on the prior page.

全年總收入為 32 億美元，比 2023 年下降 53%，主要原因是產品銷售下降，我在上一頁討論過這一點。

Other revenue contributed $127 million for the year, reflecting grant revenue, collaboration, licensing and royalty revenue.

其他收入全年貢獻了 1.27 億美元，包括贈款收入、合作收入、授權收入和特許權使用費收入。

Cost of sales for the full year 2024 was $1.5 billion or 47% of net product sales.

2024 年全年銷售成本為 15 億美元，佔淨產品銷售額的 47%。

Excluding the $0.2 billion noncash resizing charge, this would have been 39% and below our previous guidance of 40% to 45%.

不包括 2 億美元的非現金調整費用，這一比例將達到 39%，低於我們先前預期的 40% 至 45%。

This represents a $3.2 billion decrease from 2023 due to lower manufacturing resizing charges as well as lower inventory write-downs and reduced unutilized manufacturing capacity costs, all of which reflect improved efficiency.

這比 2023 年減少了 32 億美元，因為製造調整費用降低、庫存減記減少以及未利用的製造能力成本減少，所有這些都反映了效率的提高。

R&D expenses for the year were $4.5 billion, down 6% from 2023.

全年研發費用為 45 億美元，較 2023 年下降 6%。

The decrease was largely due to lower clinical trial and manufacturing costs as well as fewer upfront payments for collaboration agreements.

下降的主要原因是臨床試驗和製造成本降低以及合作協議預付款減少。

We did, however, purchase two priority review vouchers during the year, which offset some of those savings.

然而，我們確實在今年購買了兩張優先審查券，抵消了部分節省。

For the full year, SG&A expenses totaled $1.2 billion, a 24% decrease compared to 2023.

全年銷售、一般及行政開支總計 12 億美元，較 2023 年下降 24%。

The decrease reflects disciplined cost management across the organization.

這一下降反映了整個組織嚴格的成本管理。

We have continued to build capabilities and build -- bring more functions in-house, allowing us to reduce reliance on external consultants while improving operational efficiency.

我們不斷建立能力並引入更多內部功能，從而減少對外部顧問的依賴，同時提高營運效率。

Additionally, these savings were exported by better leveraging digital technology and artificial intelligence to streamline operations.

此外，透過更好地利用數位技術和人工智慧來簡化運營，這些節省的資金得以實現。

We reported an income tax benefit of $46 million for the full year compared to an income tax expense of $772 million in 2023.

我們報告全年的所得稅收益為 4,600 萬美元，而 2023 年的所得稅支出為 7.72 億美元。

The shift is mainly due to the global valuation allowance we established last year on most of our deferred tax assets, which continues to impact our tax position.

這種轉變主要是由於我們去年對大多數遞延稅務資產建立了全球估值準備金，這繼續影響我們的稅務狀況。

Net loss for the year was $3.6 billion compared to $4.7 billion in 2023, with a loss per share of $9.28 compared to $12.33 in the prior period.

全年淨虧損為 36 億美元，而 2023 年為 47 億美元，每股虧損為 9.28 美元，而上一期為 12.33 美元。

Moving to slide 11.

移至第 11 張投影片。

We want to highlight the significant reduction in our operating expenses in 2024.

我們要強調的是，2024 年我們的營運費用將大幅減少。

On a GAAP basis, cost declined $3.9 billion, from $11.1 billion to $7.2 billion.

根據 GAAP 標準，成本下降了 39 億美元，從 111 億美元降至 72 億美元。

Excluding resizing charges of $1.6 billion and $0.2 billion for 2023 and 2024, respectively, we reduced operating expenses by $2.6 billion compared to 2023, driven by manufacturing footprint resizing, pricing renegotiations, R&D prioritization, volume reductions and a greater use of digital tools to improve efficiency.

除 2023 年和 2024 年分別為 16 億美元和 2 億美元的調整費用外，我們的營運費用與 2023 年相比減少了 26 億美元，這得益於製造足跡調整、價格重新談判、研發優先化、產量減少以及更多地使用數位工具來提高效率。

Additionally, both 2023 and 2024 operating expenses included noncash costs of $0.9 billion and $0.6 billion, respectively, related to stock-based compensation and depreciation and amortization.

此外，2023 年和 2024 年的營運費用分別包括與股票薪酬和折舊和攤提相關的 9 億美元和 6 億美元的非現金成本。

If we would exclude the manufacturing footprint resizing charges, stock-based compensation and depreciation, our defined cash costs were $8.9 billion in 2023 and $6.3 billion in 2024, representing a year-over-year decline of $2.6 billion.

如果我們排除製造足跡調整費用、股票薪酬和折舊，我們的定義現金成本在 2023 年為 89 億美元，在 2024 年為 63 億美元，年減 26 億美元。

To avoid double counting, please note that in 2023, there was approximately $300 million of depreciation and amortization included in the $1.6 billion of resizing charges.

為了避免重複計算，請注意，2023 年，16 億美元的調整規模費用中包含了約 3 億美元的折舊和攤提。

We are committed to drive additional cost efficiencies in 2025 and beyond by prioritizing investments to support the 10 product launches over the next three years.

我們致力於在 2025 年及以後透過優先投資支持未來三年內 10 款產品的發布來提高成本效率。

Our 2025 GAAP expenses are projected at $6.4 billion in 2025, which includes $0.9 billion of noncash charges from stock-based compensation, depreciation and amortization.

我們預計 2025 年 GAAP 費用為 64 億美元，其中包括股票薪酬、折舊和攤提產生的 9 億美元非現金費用。

Excluding those items, we project a cash cost of $5.5 billion.

除這些項目外，我們預計現金成本為 55 億美元。

This represents an approximately $1 billion year-over-year reduction from our prior 2024 projection of $6.5 million.

這比我們先前預測的 2024 年 650 萬美元減少了約 10 億美元。

We are also planning for an additional $0.5 billion of expense reduction in 2026 as we continue to drive efficiencies across all areas of the business.

隨著我們繼續提高所有業務領域的效率，我們也計劃在 2026 年額外削減 5 億美元的開支。

Now let's turn to our financial framework for 2025.

現在讓我們來談談2025年的財務架構。

We expect total revenue in 2025 to be in the range of $1.5 billion to $2.5 billion, with first half sales of approximately $0.2 billion, reflecting the seasonality of our respiratory vaccine business.

我們預計 2025 年的總收入將在 15 億美元至 25 億美元之間，上半年的銷售額約為 2 億美元，這反映了我們呼吸道疫苗業務的季節性。

As discussed with investors in January, our wider guidance reflects 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, Canada and the UK.

正如一月份與投資者討論的那樣，我們更廣泛的指導反映了疫苗接種率、競爭激烈的市場環境、RSV 市場的規模以及我們在澳洲、加拿大和英國的工廠許可和產品批准時間的不確定性。

As a reminder, we filed three products to the FDA in 2024, and we are not including any new product revenue in our guidance range.

提醒一下，我們在 2024 年向 FDA 提交了三種產品，並且在我們的指導範圍內不包括任何新產品收入。

Also, we expect the revenue and R&D expense from our recently announced pandemic influenza program to be relatively immaterial in 2025, and is embedded in our guidance.

此外，我們預計，我們最近宣布的大流行性流感計畫的收入和研發費用在 2025 年將相對不重要，並且已包含在我們的指導中。

Positive [sales] is projected to be approximately $1.2 billion, reflecting continued improvements in manufacturing efficiency and lower expected inventory write-offs offset by increased costs associated with the go-live of our new manufacturing sites in Australia, Canada and the UK.

預計正[銷售額]約為 12 億美元，反映出製造效率的持續提高和預期庫存註銷的降低，但與我們在澳洲、加拿大和英國的新製造基地投入使用相關的成本增加相抵消。

R&D expenses are anticipated to be approximately $4.1 billion as we continue to invest in our late-stage pipeline, while maintaining financial discipline.

由於我們將繼續投資後期產品線，同時保持財務紀律，預計研發費用約為 41 億美元。

SG&A expenses are expected to be approximately $1.1 billion, reflecting a continued focus on efficiency while supporting our commercial execution.

銷售、一般及行政開支預計約為 11 億美元，反映出我們在支持商業執行的同時持續注重效率。

We expect taxes to be negligible in 2025.

我們預計 2025 年的稅收將會非常低。

Capital expenditures are projected to be approximately $0.4 billion.

資本支出預計約 4 億美元。

This increase from our prior guidance of $0.3 billion is primarily due to the timing of spend between 2024 and 2025. 2024 actual capital expenditures was approximately $150 million below our prior guidance.

與我們先前預期的 3 億美元相比，這一成長主要是由於 2024 年至 2025 年之間的支出時間。

Some of that reduction was attributable to prioritization changes, but the majority of the impact was timing of spend between 2024 and 2025.

部分減少歸因於優先順序的變化，但大部分影響是 2024 年至 2025 年之間的支出時間。

We expect to end 2025 with approximately $6 billion in cash and investments.

我們預計 2025 年底的現金和投資將達到約 60 億美元。

In summary, 2024 was a year of financial discipline, and we are well positioned as we enter 2025.

總而言之，2024 年是財務紀律的一年，進入 2025 年，我們已經做好了充分準備。

We remain committed to managing costs, optimizing our operations and investing in our future growth.

我們將繼續致力於管理成本、優化營運和投資未來成長。

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.

謝謝你，Jamey，大家早安或下午好。

Slide 15 shows the prioritized programs we highlighted at our R&D Day in September.

投影片 15 展示了我們在 9 月研發日上重點介紹的優先項目。

As Stephane mentioned earlier, we are focused on pursuing these 10 approvals over the next three years to drive growth.

正如 Stephane 之前提到的，我們專注於在未來三年內獲得這 10 項批准以推動成長。

We've now filed for approval for three respiratory vaccines, our next-gen COVID vaccine, our RSV vaccine for high-risk adults ages 18 to 59 and our flu COVID combination vaccine for people aged 50 and older.

我們目前已申請批准三種呼吸道疫苗，即下一代 COVID 疫苗、針對 18 至 59 歲高風險成人的 RSV 疫苗以及針對 50 歲及以上人群的流感 COVID 聯合疫苗。

Most of the other seven prioritized programs are in pivotal studies, and the remainder are expected to begin their pivotal studies in the near future.

其餘七個優先項目大部分處於關鍵研究階段，其餘項目預計在不久的將來進行關鍵研究。

Slide 16 highlights the most recent updates from our late-stage portfolio.

投影片 16 重點介紹了我們後期投資組合的最新更新。

As a reminder, in September, we presented positive efficacy and immunogenicity data from our next-gen COVID vaccine mRNA-1283.

提醒一下，9 月份，我們公佈了下一代 COVID 疫苗 mRNA-1283 的積極功效和免疫原性數據。

We have since filed for approval in multiple jurisdictions, and have a PDUFA date of May 31, in the United States.

我們已經在多個司法管轄區提交了批准申請，美國的 PDUFA 日期為 5 月 31 日。

Also in September, we shared positive Phase III data for our RSV vaccine in high-risk adults ages 18 to 59.

此外，在 9 月，我們分享了針對 18 至 59 歲高風險成人的 RSV 疫苗 III 期臨床試驗的積極數據。

This vaccine has also been filed for approval in multiple countries, with a PDUFA date of June 12 in the United States.

這款疫苗也已在多個國家提交批准，在美國的PDUFA日期為6月12日。

For our combination flu COVID vaccine, we previously shared positive Phase III immunogenicity and safety data.

對於我們的流感 COVID 聯合疫苗，我們之前分享了積極的 III 期免疫原性和安全性數據。

And on the basis of that data, we filed for approval at the end of last year in the United States and other countries.

基於這些數據，我們在去年年底向美國和其他國家提交了批准申請。

We have previously demonstrated efficacy for the COVID component of the vaccine, demonstration of efficacy for the flu component may ultimately be required for approval.

我們之前已經證明了疫苗中 COVID 成分的有效性，最終可能需要證明流感成分的有效性才能獲得批准。

To that end, our stand-alone flu vaccine, mRNA-1010, is currently in a Phase III efficacy study that is accruing cases rapidly.

為此，我們獨立的流感疫苗 mRNA-1010 目前正處於 III 期療效研究階段，病例正在迅速增加。

Based on the current pace of case accrual, we are optimistic that we will be able to conduct the first analysis of efficacy for our flu vaccine at the end of the currency.

根據目前病例增加的速度，我們有信心在今年年底對我們的流感疫苗進行首次療效分析。

Now turning to our nonrespiratory portfolio.

現在轉向我們的非呼吸產品組合。

Starting with our latent and other virus vaccines.

從我們的潛伏性病毒和其他病毒疫苗開始。

For our CMV vaccine, we announced last month that the Data and Safety Monitoring Board informed us that the early efficacy criteria was not met, and recommended that the study continue to its final analysis.

對於我們的 CMV 疫苗，我們上個月宣布數據和安全監測委員會通知我們未滿足早期療效標準，並建議研究繼續進行到最終分析。

We remain blinded to the study and continue to expect the results for the final analysis later this year.

我們仍然不知道這項研究並繼續期待今年稍後的最終分析結果。

Our Norovirus vaccine Phase III study is fully enrolled in the Northern Hemisphere, and we are preparing to enroll participants for the upcoming Southern Hemisphere season.

我們的諾羅病毒疫苗第三階段研究已在北半球全面招募參與者，我們正在準備為即將到來的南半球季節招募參與者。

The trial is currently on FDA clinical hold in the US, following a single case of syndrome, which remains under investigation.

由於出現一例綜合徵病例，該試驗目前在美國被 FDA 暫停臨床研究，該病例仍在調查中。

Given that enrollment had already completed for this season, we do not currently expect any impact on time lines, while we complete the investigation and update trial documents with this information.

鑑於本賽季的報名已經完成，我們目前預計不會對時間表產生任何影響，同時我們將完成調查並使用此資訊更新試驗文件。

In oncology, we and our partner, Merck, have multiple late-stage studies underway evaluating INT or mRNA-4157 in combination with KEYTRUDA.

在腫瘤學領域，我們和我們的合作夥伴默克正在進行多項後期研究，評估 INT 或 mRNA-4157 與 KEYTRUDA 的聯合使用。

The first of which, adjuvant melanoma, is part of our 10 prioritized program.

其中第一個，輔助性黑色素瘤，是我們十個優先項目的一部分。

The Phase III for this is now fully enrolled.

研究的第三階段目前已全部完成招募。

Two additional Phase III studies are underway in non-small cell lung cancer, and there are tworandomized Phase II trials ongoing in high-risk muscle-invasive bladder cancer and adjuvant renal cell carcinoma.

另外兩項針對非小細胞肺癌的 III 期研究正在進行中，另外兩項針對高風險肌層浸潤性膀胱癌和輔助性腎細胞癌的隨機 II 期試驗正在進行中。

In rare diseases, propionic acidemia, or PA, is in its registrational study, and methylmalonic acidemia, or MMA, we have -- with MMA, we have agreed with FDA on our pivotal study design and expect to start that study in 2025.

在罕見疾病方面，丙酸血症（PA）正在接受註冊研究，而甲基丙二酸血症（MMA）我們已經與 FDA 就 MMA 的關鍵研究設計達成一致，預計將於 2025 年開始該研究。

With that, I'll now hand it back to Stephane.

說完這些，我現在將發言權交還給史蒂芬 (Stephane)。

Thank you, Stephen and Jamey.

謝謝你，史蒂芬和傑米。

For 2025, we have three priorities.

面向2025年，我們有三個重點。

Priority one is to sales of approved products.

首要任務是銷售已獲批准的產品。

Priority two is to focus on our late-stage pipeline, where we believe we have up to 10 product approvals over the next three years, which will drive sales growth and diversification.

第二個優先事項是專注於我們的後期產品線，我們相信未來三年我們將有多達 10 個產品獲得批准，這將推動銷售成長和多樣化。

Priority three is to deliver cost efficiency across the business.

第三個優先事項是提高整個企業的成本效益。

Let me take you through each of these.

讓我帶你逐一了解這些。

Our first priority is to review those backs and our vaccines.

我們的首要任務是檢查這些背部和我們的疫苗。

Importantly, we enter 2025 with two approved products, which gives us a better competitive positioning that when we enter 2024.

重要的是，我們在進入 2025 年時將擁有兩款獲批產品，這將使我們比進入 2024 年時擁有更好的競爭定位。

We have full contracting in the US We expect to better compete in the respiratory vaccine market.

我們在美國有全面的承包合同，我們希望在呼吸道疫苗市場上更好地競爭。

In addition, upcoming MREL approvals outside the US should also add to sales in 2025.

此外，美國以外地區即將獲得的 MREL 批准也將增加 2025 年的銷售量。

Priority two, we are focused on delivering up to 10 products approval over the next three hree years, which we believe will drive sales growth.

第二大重點是，我們致力於在未來三年內獲得多達 10 種產品的批准，我們相信這將推動銷售成長。

Together, these 10 expected products target the total addressable market of over $30 billion.

總之，這 10 款預期產品的目標市場總額將超過 300 億美元。

Priority three, there is a cost efficiency across the business.

第三大優先事項是提高整個企業的成本效益。

We've demonstrated our commitment to cost savings by the $2.6 billion cost reduction we made in 2024.

我們在 2024 年削減了 26 億美元的成本，這表明我們致力於節省成本。

We will continue to focus on improving efficiency costs across the entire company across manufacturing, across and across SG&A in 2025, but also in 2026.

我們將持續致力於在 2025 年以及 2026 年提高整個公司的製造、銷售、一般及行政管理費用的效率成本。

For our efficiency program, we're reducing cash costs to an estimated $5.5 billion in 2025 and $5 billion in 2026.

對於我們的效率計劃，我們將把現金成本削減至 2025 年的 55 億美元和 2026 年的 50 億美元。

This brings our total cash cost reduction to well over [$1 billion] over these two years from a $6.3 billion in 2024.

這使得我們的總現金成本從 2024 年的 63 億美元減少到兩年內的 [10 億美元] 以上。

We will continue to address our cost structure to ensure we breakeven on a cash cost basis no later than 2028.

我們將繼續解決我們的成本結構問題，以確保不遲於 2028 年在現金成本基礎上實現收支平衡。

In the -- to be very clear.

在——非常清楚。

If needed, we will reduce our cost structure further than the [$5 billion] cash cost level if our sales objectives are not met.

如果需要的話，如果我們的銷售目標沒有達到，我們將進一步降低成本結構，使其低於[50億美元]的現金成本水準。

For products, we expect important milestones.

對於產品，我們期待重要的里程碑。

We filed three years of move forward to having the final reason to our Phase III study in 2025, vaccine Phase III studies and the timing of data that will be subject to we will also be subject with -- For PA, we're already data from our retraction study, and we expect to start researching study -- this year.

我們提交了為期三年的申請，以便在 2025 年獲得 III 期研究的最終結果，疫苗 III 期研究和數據的時間安排也將取決於我們 — — 對於 PA，我們已經從撤回研究中獲得了數據，我們預計今年將開始研究。

We will continue to focus on the possible impact to people

我們將繼續關注對人們可能產生的影響

.

。

Our offering of products and pipeline are promising work, [two] approved products and fixed base for pivotal studies ongoing.

我們提供的產品和管道都是有前景的工作，[兩種]已批准的產品和正在進行的關鍵研究的固定基礎。

So our money platform is working.

所以我們的貨幣平台正在運作。

We've demonstrated progress in our cost reduction program.

我們的成本削減計劃已取得進展。

We have shown that we have a financial discipline to achieve our goals and fulfill our mission.

我們已經證明，我們有財務紀律來實現我們的目標和完成我們的使命。

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) Ellie Merle, UBS.

(操作員指示) Ellie Merle，瑞銀。

Can you help us understand the breakdown of the R&D spend across your program?

您能幫助我們了解貴項目的研發知識嗎？

So if you needed to or wanted to reduce R&D spend further, how much flexibility is there on the expense structure there for, say, further cuts in the 2026 time frame?

因此，如果您需要或想要進一步削減研發支出，那麼在 2026 年的時間範圍內進一步削減，費用結構有多大的彈性？

And then just a second question.

還有第二個問題。

On the clinical hold on Norovirus, can you give any more detail around sort of this, why one case of GBS prompted the clinical hold?

關於諾羅病毒的臨床暫停，您能否詳細說明一下，為什麼一例格林-巴利綜合症病例會導致臨床暫停？

And yes, adding more color surrounding the situation there would be helpful.

是的，增加更多有關那裡的情況的色彩會有所幫助。

Yes.

是的。

Thanks, Ellie, for the questions.

謝謝艾莉提問。

Maybe I'll address the first one on R&D.

也許我會討論第一個有關研發的問題。

So we still think there's a lot of room to be reduced and a lot of flexibility.

因此我們仍然認為還有很大的削減空間和很大的靈活性。

So as a reminder, we're guiding $4.1 billion for 2025.

因此提醒一下，我們預計 2025 年的投資額為 41 億美元。

And in R&D Day, we said we would take it down by $1.1 billion from the $4.8 billion level by 2027.

在研發日，我們表示到 2027 年將把這一數字從 48 億美元減少 11 億美元。

So that suggests a number of about $3.6 billion, $3.7 billion.

所以這意味著數字約為 36 億美元、37 億美元。

To answer your question on what we're spending on, that's still back primarily over 50% of our trial spend, and therefore, overhead is related to respiratory trials, which, as you know, we expect to roll off over this year and the following year.

回答您關於我們支出問題的問題，這主要仍占我們試驗支出的 50% 以上，因此，間接費用與呼吸試驗有關，如您所知，我們預計這筆費用將在今年和明年結轉。

And then the only other Phase III trials that we started are in latent disease, in oncology for Norovirus, and CMV and INT, and we expect those to be reduced over the coming years as well.

然後，我們開始的其他 III 期試驗僅針對潛伏性疾病、諾羅病毒、CMV 和 INT 的腫瘤學，我們預計未來幾年這些試驗的數量也會減少。

So we expect that there will be some flexibility beyond the $3.6 billion that we've already indicated.

因此，我們預計，除了我們已經提到的 36 億美元之外，還會有一些靈活性。

But right now, we're still monitoring the sales line, but that is an area that we could continue to reduce if need be.

但目前，我們仍在監控銷售線，但如果有必要，我們可以繼續減少這一領域。

And thank you for the second question.

感謝您的第二個問題。

I'll take it.

我要買它。

So just a little bit of context, as you alluded to, GBS does happen, obviously, in the background population.

因此，只需提供一點背景信息，正如您所提到的，GBS 顯然確實發生在背景人群中。

It's usually seen in older adults, about one to two per 100,000 participants per year or people per year.

它通常見於老年人，每年每 10 萬名參與者中約有 1 至 2 人患有該疾病。

And given we've enrolled well over 250,000 participants in studies over the last couple of years, it wouldn't be surprising to see cases in our clinical trials, as you suggested.

鑑於我們在過去幾年的研究已經招募了超過 250,000 名參與者，因此正如您所說，在我們的臨床試驗中出現病例也就不足為奇了。

And although that hasn't been associated as a risk factor with our approved vaccines, this is something that does happen.

儘管這與我們批准的疫苗無關，但這種情況確實會發生。

As it relates to this case, when we identified it, we proactively decided to pause our activities and update our study documents because we prioritize the patient safety and obviously, transparency, first and foremost.

就此案例而言，當我們發現它時，我們主動決定暫停我們的活動並更新我們的研究文件，因為我們優先考慮患者的安全，顯然透明度是首要的。

And we wanted to make sure that all that information was shared as soon as the case merged.

我們希望確保案件合併後所有資訊都能分享。

We submitted those for review with regulators globally, and the FDA has placed us on a clinical hold while they review that information in those documents.

我們已將這些文件提交給全球監管機構進行審查，FDA 在審查這些文件中的資訊時已將我們置於臨床暫停狀態。

Perhaps most importantly for study conduct, because we had enrolled and dosed everybody prior to the emergence of this case in the current season study, we really don't expect there to be any impact on the conduct of the study or its time line for readout on efficacy, which will ultimately be case driven.

對於研究的實施而言，也許最重要的是，由於我們在本季研究中出現這個病例之前就已經招募並給每個人進行了劑量測定，因此我們確實不認為這會對研究的實施或其療效讀數的時間表產生任何影響，因為這最終將由案例驅動。

So from our side, this is just about being prudent and transparent and making sure that we're prioritizing patient safety.

因此從我們的角度來看，這只是謹慎和透明的做法，並確保我們優先考慮患者的安全。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

Maybe just follow up on Norovirus.

也許只是跟蹤諾羅病毒。

What would it take for the FDA to remove the clinical hold?

FDA 需要做什麼才能取消臨床暫停令？

What kind of outcome that we deem to be okay?

什麼樣的結果我們才認為可以？

And then really another question regarding the CMV, now we should see more events accrued?

然後關於 CMV 的另一個問題，現在我們應該看到更多事件的發生嗎？

Will it still happen in the first half '25?

2025年上半年還會發生這種事嗎？

Should we see the final readout?

我們應該看看最終的結果嗎？

Gena, you broke for just a second.

吉娜，你只崩潰了一秒鐘。

Could you repeat the CMV portion of the question?

您能重複一下問題的 CMV 部分嗎？

Sure.

當然。

CMV, since now we've seen additional months of events accruing, should we still be able to see the final readout in the first half '25?

CMV，既然現在我們已經看到了幾個月來的事件累積，我們是否還能在 25 年上半年看到最終的讀數？

Thank you.

謝謝。

So I think -- let me deal with that first.

所以我想——讓我先處理一下這個問題。

So yes, we continue to accrue cases in the CMV trial.

所以是的，我們在 CMV 審判中繼續累積案件。

As I said, we remain blinded to the interim analysis.

正如我所說，我們仍然看不到中期分析的結果。

We still do expect that result in 2025.

我們仍然期待 2025 年能夠達到這樣的結果。

I don't know that we've got into the specific timing, but we still do expect the result in '25.

我不知道我們是否已經確定了具體的時間，但我們仍然期待在 25 年得到結果。

As it relates to Norovirus, clinical hold, obviously, I think the FDA needs the time to review the materials we've submitted.

由於它與諾羅病毒有關，臨床暫停，顯然，我認為 FDA 需要時間來審查我們提交的資料。

They may come back with some questions.

他們可能會回來問一些問題。

If they do, we'll answer those.

如果他們提出這個問題，我們會予以回答。

But as has been suggested even in the question, a case of GBS is not necessarily unexpected.

但正如問題中所暗示的那樣，GBS 病例並不一定出乎意料。

And because we've updated the documents, we really do expect there to be minimal impact on trial conduct at this point But it will be ultimately up to the agency, what they need to see before we move forward with further enrollment.

而且因為我們已經更新了文件，我們確實希望此時對試驗進行的影響最小，但最終還是要由機構來決定，在我們進行進一步的招募之前他們需要看到什麼。

Michael Yee, Jefferies.

傑富瑞 (Jefferies) 的麥可餘 (Michael Yee)。

We had two timing questions for you guys.

我們對你們有兩個時間問題。

First, on the INT cancer vaccine, which, of course, is a really exciting product.

首先是關於 INT 癌症疫苗，這當然是一個非常令人興奮的產品。

I think previously, if you've done some math on the Phase II, it's certainly possible on the event rates that were seen in Phase II that the data could come by end of year or first half of '26 and the company has not totally dissuaded us or others from that type of timing.

我認為，如果您之前對第二階段做過一些計算，那麼根據第二階段看到的事件發生率，數據可能在年底或26年上半年得出，而且該公司並沒有完全勸阻我們或其他人不要採用這種時間安排。

Do you generally agree with that timing?

您大體上同意這個時間安排嗎？

And can you shed some light on how to think about the powering for the INT cancer vaccine primary end point?

您能否解釋一下如何考慮 INT 癌症疫苗主要終點的驅動因素？

And then similarly, with the Norovirus, I think you mentioned that you're enrolling the Southern Hemisphere but completed the Northern.

同樣地，對於諾羅病毒，我想您提到過，您招募了南半球的人，但完成了北半球的人。

Do you need both to hit the primary or to hit the event rate and just help us understand the timing of that despite the fact that it's on hold, the Northern which already completed enrollment.

您是否需要同時達到初選或活動率，並幫助我們了解時間安排，儘管它處於擱置狀態，但北方已經完成了註冊。

Thanks for your questions.

感謝您的提問。

So first on INT, there are some differences between the study population between the Phase II and the Phase III.

首先關於 INT，第二階段和第三階段的研究族群存在一些差異。

And so we will want to be guided by the actual event accrual, a case accrual rate, the relapse rate in the Phase III study before we feel confident that we could offer a timing on that.

因此，我們希望以實際事件累積、病例累積率和第三階段研究中的復發率為指導，然後我們才能有信心提供時間安排。

And so as we have started to accrue cases, the study, as you know, is fully enrolled.

因此，隨著我們開始累積病例，正如你所知，這項研究已經完全招募了患者。

So there are to be events that start to happen.

因此將會有一些事件開始發生。

We'll have a better sense of that.

我們將對此有更好的認識。

Certainly, 2026 seems possible, plausible.

當然，2026 年似乎是可能的，而且是合理的。

But whether or not it could be on the early side of that or the late side of that, we just don't know at this point, it is event driven.

但目前我們還不知道它是發生在早期還是晚期，它是事件驅動的。

And so more as we have information in the future.

隨著我們未來掌握更多信息，我們將來也會提供更多資訊。

On the question of Norovirus, so we have -- we fully enrolled and fully dosed the Northern Hemisphere study, which is the majority of the study.

關於諾羅病毒的問題，我們已經全面招募並完成了北半球的研究，這是研究的主要內容。

But given epidemiology, we also wanted to enroll some participants in Southern Hemisphere geographies.

但考慮到流行病學，我們也想招募一些南半球地區的參與者。

At the end of the day, we will also be case driven, so you ultimately need cases of Norovirus towards that efficacy endpoint because the majority -- the sizable majority study is completely enrolled now.

歸根結底，我們還將以案例為導向，因此最終需要諾羅病毒病例才能達到療效終點，因為大多數 - 相當大比例的大多數研究現在都已經完全招募完畢。

That's Northern Hemisphere is completely enrolled, which is the majority of the participants we intended.

北半球的參與者已經全部報名，占我們預期參與者的大多數。

It's possible that we won't need Southern Hemisphere participants.

我們可能不需要南半球的參與者。

But we do intend to enroll Southern Hemispheres if we want broader epidemiology towards that final endpoint.

但如果我們想要更廣泛的流行病學研究以達到最終目的，我們確實打算招募南半球的研究者。

So again, we don't know when that will happen.

所以我們不知道那會在什麼時候發生。

We do currently hope that we're sufficiently powered in this season to see efficacy, but if more participants are needed, then of course, we will enroll them to accrue more cases towards that efficacy endpoint.

我們目前確實希望我們在這個季節有足夠的能力來看到療效，但如果需要更多的參與者，那麼當然，我們會招募他們來累積更多的病例以達到該療效終點。

Salveen Richter, Goldman Sachs.

高盛的薩爾文·里希特（Salveen Richter）。

Could you help us understand what the clinical bar is for the Norovirus program?

您能幫助我們了解諾羅病毒計畫的臨床標準是什麼嗎？

And then on the INT portfolio, will we get any data or just enrollment updates for the programs beyond melanoma?

然後在 INT 投資組合中，我們會獲得任何數據還是只是黑色素瘤以外計畫的入學更新？

So the -- on the clinical bar for Norovirus, obviously, there are other vaccines out there for gastrointestinal infections, and others, where we will want to show a meaningful decrease in the rate of moderate to severe gastrointestinal symptoms.

因此，在諾羅病毒的臨床測試中，顯然還有其他針對胃腸道感染的疫苗，以及其他疫苗，我們希望顯示中度至重度胃腸道症狀的發生率顯著下降。

Those are really where the burden of disease happens, particularly in higher risk populations like older adults or the immuno-compromised.

這些才是疾病負擔真正發生的地方，特別是老年人或免疫功能低下者等高風險族群。

We'll look at a pretty broad range of endpoints as secondary and exploratory influence as well, things like hospitalization, utilization of health care services.

我們也將把相當廣泛的終點視為次要和探索性影響，例如住院率、醫療服務的使用率。

We have not disclosed our target product profile for that yet or the powering assumptions we have in those interim analyses.

我們尚未揭露我們的目標產品概況或這些中期分析中的主要假設。

And so I won't do that here.

所以我不會在這裡這麼做。

We will, perhaps, in the future, provide an update on that, but we will be looking for a meaningful reduction in the rate of moderate to severe acute gastroenteritis.

我們或許會在將來提供有關這方面的最新信息，但我們希望中度至重度急性胃腸炎的發病率能有顯著降低。

As for INT, obviously, we're all looking forward to the melanoma adjuvant melanoma Phase III readout.

至於 INT，顯然，我們都期待黑色素瘤輔助治療黑色素瘤 III 期的結果。

As you know, and as I mentioned, there are additional Phase IIIs as well as tworandomized Phase IIs, including bladder cancer and renal cell carcinoma, which, depending on the rate of accrual of events, could have read outs that we would be updating on as well in the coming years.

如你所知，正如我所提到的，還有其他 III 期研究以及兩個隨機 II 期研究，包括膀胱癌和腎細胞癌，根據事件累積的速度，可能會讀出我們在未來幾年也會更新的信息。

Terence Flynn, Morgan Stanley.

摩根士丹利的特倫斯弗林 (Terence Flynn)。

Maybe a two-part for me.

對我來說也許分為兩個部分。

Just wondering if you can confirm if you still have not seen any cases of GBS with your RSV vaccine?

我只是想知道您是否可以確認在接種 RSV 疫苗後是否仍未發現任何格林-巴利綜合症病例？

And then I know you filed for approval for the COVID flu combo vaccine, and it sounds like now you're waiting for some vaccine efficacy data.

然後我知道你已經申請了 COVID 流感組合疫苗的批准，聽起來現在你在等待一些疫苗功效數據。

Can you tell us anything more there about what the bar is?

您能告訴我們有關酒吧的更多資訊嗎？

Is it only on the flu side?

這只是流感嗎？

Or do you need vaccine efficacy for both COVID as well and kind of what level of protection you need to see?

或者您需要對 COVID 疫苗同樣有效，以及您需要看到什麼程度的保護？

Flynn, thanks for both questions.

弗林，謝謝你的兩個問題。

So first, I can confirm that GBS has not yet or has not been identified as a risk factor for our RSV vaccine or our COVID vaccine today.

因此，首先，我可以確認 GBS 尚未被確定為我們今天的 RSV 疫苗或 COVID 疫苗的風險因素。

And so obviously, we'll continue to track that closely, but that's encouraging.

顯然，我們將繼續密切關注，但這令人鼓舞。

On the combo study, so we have demonstrated efficacy for the COVID component.

在組合研究中，我們已經證明了 COVID 成分的有效性。

As you may remember, mRNA-1283 had a successful efficacy study in -- that we announced last year.

您可能還記得，mRNA-1283 的功效研究已取得成功——我們去年宣布了這一消息。

And that is the COVID component of the combination vaccine so to satisfy that requirement.

這就是聯合疫苗的 COVID 成分，可以滿足這項要求。

As for the flu vaccine, we have had multiple Phase III readouts in our flu vaccine as well as for the combo vaccine demonstrating non-inferior or superior immunogenicity and a good safety profile for those

至於流感疫苗，我們的流感疫苗和組合疫苗已進行了多次 III 期試驗，結果顯示其免疫原性不劣於或優於其他疫苗，且安全性良好。

.

。

But we have not yet demonstrated efficacy for the flu component of that vaccine.

但我們尚未證明該疫苗的流感成分的有效性。

That trial, as I mentioned, is actually ongoing right now.

正如我所提到的，該審判實際上目前正在進行中。

And given that it is a robust flu season in the Northern Hemisphere, as many folks know, and given the case accrual rate we see there, we do expect that we'll -- we're actually quite optimistic we'll be able to kind of the first interim analysis of efficacy at the end of this current season.

鑑於目前是北半球流感高發季節，正如許多人所知，鑑於那裡的病例累積率，我們確實預計——我們實際上非常樂觀，我們將能夠在本季度末進行第一次中期療效分析。

And so that would then be the demonstration of efficacy for the flu component of the combo vaccine.

這樣，這就證明了聯合疫苗中流感成分的有效性。

Tyler Van Buren, TD Cowen.

泰勒·範布倫（Tyler Van Buren），TD Cowen。

Regarding Thank for taking question.

關於感謝您提出問題。

CMV, just to confirm, even though the criteria on for early efficacy was not met at the interim, is it still possible that higher vaccine efficacy threshold from the first interim could still be reached from the final analysis due to a wide confidence interval with fewer patients at the time of the CMV review?

CMV，只是想確認一下，即使在此期間早期療效的標準沒有得到滿足，由於 CMV 審查時置信區間較寬且患者較少，從最終分析來看，是否仍有可能達到第一階段更高的疫苗療效閾值？

Or do you think that's less likely?

或者您認為這種可能性較小？

Thanks for the question.

謝謝你的提問。

So what we -- if you look at the tower that we had at that first interim analysis, it actually was intended as an early look, but not sufficiently powered that you would have high compound if it was in between efficacy.

所以，如果您看一下我們在第一次中期分析中所擁有的塔，它實際上只是作為早期觀察而設計的，但如果它在功效之間，則其功率不足以產生高複合功率。

And for that reason, it is still very much possible that at the final analysis with many more cases, the confidence interval is narrow and what we see as a point estimate for efficacy that is favorable from our perspective, meets or exceeds our expectations for the target

因此，在最終分析中，由於病例數更多，置信區間較窄，從我們的角度來看，我們認為療效的點估計值是有利的，符合或超出了我們對目標的預期，這種情況仍然很有可能發生。

.

。

The most important thing to say, though, is that we remain completely blind to this.

但最重要的是，我們對此仍然一無所知。

All we know is that the confidence interval did not exclude the lower bound target.

我們只知道信賴區間並未排除下限目標。

And given the powering of the study that -- for that interim analysis, does not necessarily surprising, stopping for early efficacy early criteria and would have been an upside scenario in our view.

並且考慮到研究的力量—對於該中期分析而言，停止早期療效的早期標準並不一定令人驚訝，在我們看來這將是一個好的情景。

So we remain blinded.

所以我們仍然盲目。

We will accrue the full number of cases.

我們將累計全部案件數量。

We continue doing this in that study, and then we'll look to that final announces, which is actually the fully powered analysis for assessing against our target product profile.

我們在該研究中繼續進行此項工作，然後我們會專注於最終公告，這實際上是針對我們的目標產品概況進行評估的完全有力的分析。

Luca Issi, RBC Capital.

伊西 (Luca Issi)，RBC Capital。

Great.

偉大的。

Maybe, Stephane, big picture.

也許吧，史蒂芬，大局。

We all know that you have worked very closely with the Trump administration during the pandemic.

我們都知道，您在疫情期間與川普政府密切合作。

But have you talked to either the President, RFK or any of the representative this time around?

但這次你和總統、羅伯特甘迺迪或任何代表談過嗎？

If so, what has been the message that you have been hearing from them?

如果是，你從他們那裡聽到了什麼訊息？

I think any color there would be much appreciated.

我認為任何顏色都會受到歡迎。

And then maybe second, Stephen, on Norovirus, can you just talk about the timing of the GBS case?

然後也許是第二個問題，史蒂芬，關於諾羅病毒，您能談談格林-巴利綜合症病例發生的時間嗎？

Is that something that occurs soon after the individuals receive the vaccine or maybe many months after that?

這是人們接種疫苗後不久就會發生的事情，還是在接種疫苗數月後就會發生的事情？

I'm just trying to understand the correlation versus causation here.

我只是想了解這裡的相關性和因果關係。

So again, any color, much appreciated.

所以，無論什麼顏色，我都十分感激。

Thank you for the question.

感謝您的提問。

So as we work productively with the Trump administration in the President Trump's first mandate, and we look forward to working with a new team as they get confirmed by the Senate and the different members.

因此，在川普總統的第一個任期內，我們與川普政府進行了富有成效的合作，我們期待在參議院和不同成員的確認後與新團隊合作。

Vaccine are variable and piece of keeping people healthy, and we look forward to having those discussions as people get confirmed.

疫苗是可變的，也是維持人們健康的一部分，我們期待在人們得到確認後進行這些討論。

Stephen?

史蒂芬？

Yes.

是的。

And on the Norovirus case, as you probably will note, we've enrolled about 20,000 participants in that study in just the last couple of months.

關於諾羅病毒病例，您可能已經注意到，僅在過去幾個月中我們就招募了大約 20,000 名參與者參與這項研究。

It's all been relatively rapid enrollment for the current Norovirus season.

對於當前的諾羅病毒季節來說，這一切都是相對較快的登記。

For that reason, you can imagine that it's relatively proximal, which is why we're being cautious and communicating around it, first and foremost, with participants, investigators and regulators just so they have that information.

因此，你可以想像它是相對較近的，這就是為什麼我們要謹慎並就此進行溝通，首先是與參與者、調查人員和監管機構進行溝通，以便他們獲得這些資訊。

Now to the point of correlation versus causation, it's important to note that in this case, these extremely rare events that do happen, it's very hard of -- to finally determine cause or relationship.

現在回到相關性與因果關係的問題，值得注意的是，在這種情況下，這些確實發生的極其罕見的事件很難最終確定原因或關係。

And so other than reporting it that it happened around this time and investigating it, thoroughly communicating around it, we may never have an interview on that.

因此，除了報告此事發生在此時並進行調查、徹底溝通之外，我們可能永遠不會就此事進行採訪。

But yes, respect for the confidentiality for that participant and more generally, I don't think I would offer any more information other than we continue to investigate it and see if what the potential causes would be.

但是是的，為了尊重該參與者的保密性，更普遍地說，我認為我不會提供更多信息，除了我們繼續調查並查看潛在原因是什麼。

Cory Kasimov, Evercore ISI.

Cory Kasimov，Evercore ISI。

This is [Adi] on for Cory.

這是 Cory 的 [Adi]。

I wanted to ask on what possible changes have you seen in the past month that has caused the bump to expense guidance already?

我想問一下，在過去的一個月中，您看到哪些可能的變化導致費用指引出現上漲？

To expense guidance, Adi?

要費用指導，阿迪？

The increase in R&D and SG&A spend?

研發和銷售、一般及行政開支增加嗎？

I think -- so I don't know if it's a bit confusing.

我認為——所以我不知道這是否有點令人困惑。

So we've been basically talking about twodifferent sets of numbers, neither have changed.

所以我們基本上一直在談論兩組不同的數字，它們都沒有改變。

One is our GAAP cost, Adi, and one, which includes stock-based compensation and depreciation and amortization.

一個是我們的 GAAP 成本，Adi，另一個包括股票薪酬以及折舊和攤提。

So maybe that's what you're referring to versus what we define as cash costs, which excludes those twonumbers, which have not changed.

所以也許這就是你所指的，與我們定義的現金成本相比，它不包括這兩個沒有變化的數字。

And as a reminder, those numbers were close to $9 billion in 2023.

提醒一下，到 2023 年，這些數字將接近 90 億美元。

We had $6.3 billion in 2024.

到 2024 年，我們的收入將達到 63 億美元。

We're guiding to $5.5 billion in 2025 and $5 billion in 2026.

我們預計 2025 年將達到 55 億美元，2026 年將達到 50 億美元。

So perhaps you're looking at the GAAP inclusion, but I -- we have not changed any estimates from our cost.

因此，也許您正在考慮 GAAP 納入，但是我 - 我們沒有改變任何成本估計。

Got it.

知道了。

And I have just one more follow-up.

我還有一個後續問題。

If you can provide any more color on the language of the PA program, the PR at GPM and today's PR suggests potential decrease in MDE sequencing.

如果您可以對 PA 程式的語言提供更多說明，GPM 的 PR 和今天的 PR 表明 MDE 排序可能會減少。

I wanted just some additional color on it.

我只是想要增加一些顏色。

Yes.

是的。

So -- as we had previously disclosed, from our ongoing clinical trial there, we have seen a significant -- a substantial decrease in the rates of metabolic decompensation events in that propionic acidemia PA study.

因此，正如我們先前所揭露的，從我們正在進行的臨床試驗來看，我們在丙酸血症 PA 研究中看到代謝失代償事件的發生率顯著下降。

And we believe and ultimately have agreed with regulators that, that is the endpoint that we will assess for the pivotal part of that study.

我們相信並且最終與監管機構達成一致，這是我們評估研究關鍵部分的終點。

We've moved forward into that pivotal phase, so what we'll be looking at is the rate of metabolic compensations or MDE, for participants prior to being on drug versus once they start treatment with that medicine.

我們已經進入了關鍵階段，因此我們將關注參與者在服藥之前和開始藥物治療後的代謝補償率或 MDE。

That rate and the reduction in it will ultimately be -- we believe the pivotal endpoint that would support registration for the drug for PA.

我們認為，該比率及其降低最終將成為支持該藥物在 PA 上註冊的關鍵終點。

And so as we move forward with new participants, as well as some older -- other participants who are already on the study, we'll be looking at that comparison on reduction in the rates of MDE.

因此，當我們有新的參與者以及一些年長的人——已經參與研究的其他參與者時，我們將對 MDE 發生率的降低進行比較。

Courtney Breen, Bernstein.

考特尼·布林，伯恩斯坦。

I wanted to kind of pivot a little bit to some of the costs as well and specifically the inventory write-downs.

我想要稍微談談一些成本，特別是庫存減記。

I think they continue to be an issue for kind of seasonal vaccines.

我認為它們仍然是季節性疫苗的一個問題。

We have to produce in advance and then see the season play out.

我們必須提前製作，然後觀察賽季的進展。

I would love to understand a little bit more about what the future looks like in this space?

我很想進一步了解這個領域的未來前景？

You're going to continue to be in a seasonal market kind of both with COVID, now with flu and with RSV.

你將繼續處於季節性市場，既有 COVID，現在還有流感和 RSV。

And so as we think about kind of projecting and manufacturing appropriately to minimize those write-downs but maximize the opportunity, what does good look like, number one, kind of what goal in terms of limited inventory write-downs?

因此，當我們考慮進行適當的預測和製造以盡量減少這些減記但最大限度地利用機會時，什麼是好的，第一，在有限庫存減記方面的目標是什麼？

And number two, kind of what are the things that you're changing to kind of continue to improve your ability to make to the?

第二，您正在改變哪些事情來繼續提升您的能力？

Yes.

是的。

Thanks for the question, Courtney.

謝謝你的提問，考特尼。

It's a great one.

這是一個很棒的經驗。

So as you know, and maybe just to step back, in 2023, I forget what the numbers are, but we've reduced this dramatically already.

所以如你所知，也許只是回顧一下，在 2023 年，我忘記了數字是多少，但我們已經大幅減少了這個數字。

But nonetheless, we did have $500 million of inventory write-downs in 2024 and about $100 million of unutilized manufacturing capacity.

但儘管如此，我們在 2024 年確實有 5 億美元的庫存減記和約 1 億美元的未利用製造產能。

And so that $600 million on $3 billion of sales, that is obviously not what good looks like yet.

因此，在 30 億美元的銷售額中，那 6 億美元顯然還不夠理想。

What I will say is much of this is related to our raw materials where we take an inventory reserve based on future demand.

我要說的是，這在很大程度上與我們的原材料有關，我們根據未來的需求進行庫存儲備。

And if you look at our inventory levels now, Courtney, we are under $300 million.

考特尼，如果你看看我們現在的庫存水平，庫存量低於 3 億美元。

I think, $270 million.

我認為是2.7億美元。

So the go forward should look much better as we project moving forward on the raw material side.

因此，隨著我們預測原材料的進展，未來的發展前景應該會更加美好。

On the excess capacity side, you're right.

關於產能過剩方面，你是對的。

We still have a fair amount of either write-offs of good product that we produce because we produced last year, for example, we assumed $4 billion in sales, and we came in at $3 billion, so we obviously overproduced.

我們生產的優質產品仍有相當數量的註銷，因為我們去年生產了這些產品，例如，我們假設的銷售額為 40 億美元，但實際銷售額只有 30 億美元，因此我們顯然生產過剩了。

And we are still going to produce to the higher end of our guidance range of $1.5 billion to $2.5 billion, which is why you see a cost of sales in the neighborhood of 50%.

我們仍將按照 15 億美元至 25 億美元的指導範圍的高端進行生產，這就是為什麼您會看到銷售成本達到 50% 左右。

But as we get better, what we're working on is matching what does that future demand look like and what is the supply that we should account for?

但隨著我們變得越來越好，我們正在努力的是匹配未來的需求是什麼樣的，以及我們應該考慮的供應是什麼？

And as an example, as we've continued to adjust for that, that's the example of the termination of a contract manufacturing agreement that we had in the fourth quarter.

舉個例子，我們一直在對此進行調整，這就是我們在第四季度終止合約製造協議的例子。

So we continue to be proactive about what is that future demand, what is the capacity we require, and you should see that come down.

因此，我們將繼續積極考慮未來的需求是什麼、我們需要的產能是什麼，你應該會看到這個數字下降。

And certainly, $600 million on $3 billion is not what we expect.

當然，30 億美元中的 6 億美元並不是我們所期望的。

We want that to be less than 10%, let's say, over time, but I'm not saying that, that will happen in the year 2025, but it will get better also because our inventory balance is down dramatically.

我們希望隨著時間的推移，這一比例會低於 10%，但我並不是說這會在 2025 年實現，但情況也會變得更好，因為我們的庫存餘額大幅下降。

Edward Tenthoff, Piper Sandler.

愛德華·坦托夫，派珀·桑德勒。

Most my questions have been answered.

我的大部分疑問都已得到解答。

But I think I saw some news maybe on the [Vertex CF] program.

但我想我看到了一些關於 [Vertex CF] 計劃的新聞。

And I was wondering if you could just kind of give us an update on what's going on there with that rare disease program?

我想知道您是否可以向我們介紹罕見疾病計畫的最新進展？

Yes.

是的。

So thank you for the question, Ed. So we continue with our partner, [Vertex], who is conducting that clinical trial.

謝謝你的提問，艾德。因此我們繼續與我們的合作夥伴[Vertex]合作進行這項臨床試驗。

So the sponsor study have the most information on it.

因此，贊助方的研究擁有最多的相關資訊。

But we continue to have the path of -- we've completed the single ascending dose portion of that trial and are now in the multiple ascending dose portion of that trial.

但我們仍將繼續前進——我們已經完成了該試驗的單次遞增劑量部分，現在正處於該試驗的多次遞增劑量部分。

That is, patients receiving treatment regularly to ultimately measure whether or not we're having an effect on respiratory measures and hopefully, overall, addressing the burden of CF in those patients that can't take the small molecule correctors.

也就是說，患者定期接受治療，最終衡量我們是否對呼吸指標產生影響，並希望整體解決那些無法服用小分子矯正劑的患者的 CF 負擔。

We do expect a readout from that multiple ascending dose trial.

我們確實期待從該多次遞增劑量試驗中獲得讀數。

I think Vertex previously guided that we expect that this year, and we will look for them to provide further updates on that timing, if they happen.

我認為 Vertex 之前曾指導過我們預計今年會實現這一目標，如果實現的話，我們將期待他們提供有關該時間的進一步更新。

Jessica Fye, JPMorgan.

摩根大通的傑西卡·菲伊 (Jessica Fye)。

I have a few follow-ups for Stephen, just from prior questions I was hoping to clarify the response on.

我對史蒂芬有一些後續問題，只是針對先前的問題，我希望澄清答案。

On Norovirus, how confident are you that the trial will not go on some equivalent of clinical hold in the Southern Hemisphere?

關於諾羅病毒，您是否有信心該試驗不會在南半球進行類似臨床暫停？

Have other global regulators confirmed they do not need a pause to review the information?

其他全球監管機構是否已經確認他們不需要暫停審查這些資訊？

Or is there a chance of stoppage there?

或者有沒有可能停下來？

For CMV, just following up on Gena's question.

對於 CMV，我只是跟進 Gena 的問題。

I think in the past, you had said the final CMV analysis could come near months after the interim, which we heard about in January.

我想，您過去曾說過，最終的 CMV 分析可能會在中期分析結束後幾個月內進行，我們在一月份就聽說過這個消息。

So should we still think of that as the first half of '25?

那麼我們仍應該將其視為 25 年上半年嗎？

Or can you clarify the prior answer?

或者您能澄清一下先前的答案嗎？

And then on the 1083 COVID flu filing, I think the press release states that approval may require a vaccine efficacy data from the Phase III flu trial.

然後關於 1083 COVID 流感申請，我認為新聞稿中指出，批准可能需要第三階段流感試驗的疫苗有效性數據。

Why is that a point of uncertainty that the FDA may require?

為什麼這是 FDA 可能要求的不確定點？

Has it been up and clear with you in your pre-submission meeting?

在提交前的會議上你已經把這些說清楚了嗎？

And then lastly for Jamey.

最後是 Jamey。

Can you recap what variables in the COVID vaccine and RSV markets would land you at the low end or the high end of your '25 guidance, like price vaccination rates, market share or stuff like that?

您能否回顧 COVID 疫苗和 RSV 市場中的哪些變數會導致您的 '25 指導目標達到低端或高端，例如價格、疫苗接種率、市場份額或諸如此類的東西？

So a lot there for me, so I'll go first and then kick you to Jamey.

對我來說有很多東西，所以我先走，然後把你踢給 Jamey。

So first, on the Northern -- the Norovirus study.

首先，關於北方​​－諾羅病毒的研究。

As we said, we will look to enroll a second season in the Southern Hemisphere.

正如我們所說，我們將期待在南半球開展第二季活動。

At present, we do not expect any delays in doing that, given that we have enrolled over 20,000 participants in that study already in Northern Hemisphere, if there were any delays, we're not sure that it would have an impact to study time line.

目前，我們預計不會出現任何延誤，鑑於我們已經在北半球招募了超過 20,000 名參與者參與研究，如果有任何延誤，我們不確定是否會對研究時間表產生影響。

But at this point, we're as confident as we can be that there won't be any in the Southern Hemisphere.

但目前，我們可以確信南半球不會有任何此類現象。

As it relates to CMV, on case accrual.

由於它與 CMV 有關，所以與案件累積有關。

The second half, we have previously said that case accrual was moving relatively quickly.

下半年，我們之前說過，案件的進展相對較快。

It continues to accrue steadily in the study.

它在研究中繼續穩步累積。

Ultimately, it's an event-driven analysis, so we can't necessarily predict the time line, but we previously indicated that we expected it perhaps mid-2025.

歸根結底，這是一個事件驅動的分析，所以我們無法預測時間線，但我們之前表示，我們預計它大概會在 2025 年中期。

We're not changing that here.

我們這裡不會改變這一點。

We continue to believe if that's possible.

我們繼續相信這是可能的。

And ultimately, again, it will depend upon the rate of case accruals, which we don't control.

最終，這將取決於案件累積率，而這是我們無法控制的。

As to 1083, and so for the flu COVID product, when we submitted the package as part of our initial exchange with regulators, we are identifying review questions that they have or issues.

至於 1083，對於流感 COVID 產品，當我們作為與監管機構初步交流的一部分提交包裹時，我們正在確定他們存在的審查問題或問題。

And as we said in our press release, in some cases, the proximity of the flu efficacy readout really does loom large on the overall review for the combination product.

正如我們在新聞稿中所說的那樣，在某些情況下，流感療效讀數的接近性確實對組合產品的整體評價產生重大影響。

And we will be -- we do expect that, that may be necessary in some cases now that, that flu readout is expected shortly.

而且我們確實預計，在某些情況下這可能是必要的，因為預計很快就會有流感數據出來。

As it relates to individual conversations with individual regulators, I'll say, we're working through their review questions in that submission, and I won't otherwise comment on the specific back and forth.

至於與各個監管機構的單獨對話，我想說的是，我們正在研究他們在提交的文件中提出的審查問題，我不會對具體的來回對話發表評論。

And with that, I guess, I'll turn it over to you, Jamey.

我想，就此，我將把話題交給你了，傑米。

Okay.

好的。

Thanks.

謝謝。

So thanks, Jess.

所以謝謝你，傑西。

Yes.

是的。

So as a reminder, on the high end, the $2.5 billion, if you exclude the unusual we saw in 2024, we called that essentially flat.

因此提醒一下，如果排除 2024 年出現的異常情況，高階的 25 億美元基本上是持平的。

So in my prepared remarks, the US came in at $1.7 billion.

因此，在我準備好的演講中，美國的出資額為 17 億美元。

It had a $200 million return reversal adjustment from the prior year, which would take that to about a $1.5 billion number.

與前一年相比，該公司進行了 2 億美元的回報逆轉調整，這使得這一數字達到約 15 億美元。

And then outside the United States, we were at $1.4 billion, and we said that there was about $400 million of advanced purchase agreements that the demand level we do not anticipate repeating.

然後在美國以外，我們的銷售額為 14 億美元，我們說有大約 4 億美元的預購協議，我們預計需求水準不會重複。

So the high end is essentially flat, Jess.

因此高端基本上是平坦的，傑西。

So you can anticipate both inside the US and outside the US, similar market share, vaccination rates.

因此，你可以預測美國國內和國外的市佔率和疫苗接種率都會相似。

We do have a little bit of uptick in RSV in the high end, but it's all together rather minimal in general.

在高階 RSV 方面，我們確實看到了一些上漲，但總體而言，這一漲幅相當小。

On the low end, it basically assumes no increase in RSV.

在低端，它基本上假設 RSV 不會增加。

In the US, you would have to expect it to go down substantially.

在美國，你必須預料到它會大幅下降。

So you'd have to expect it to go down 5% to 10% from a market share perspective.

因此從市場佔有率的角度來看，你必須預期它會下降 5% 到 10%。

Vaccination rates would have to go down again 7% to 10%.

疫苗接種率將不得不再次下降7%至10%。

Both of those things would have to happen to go down, let's say, $0.5 million.

這兩件事都必須發生，才會使金額下降，比如說，50 萬美元。

And then really the biggest factor outside the United States are the [licenser] timing of our plants in the UK., Canada and Australia.

那麼，美國以外真正的最大因素是我們在英國、加拿大和澳洲的工廠的[授權人]時間表。

So should those be licensed and registered on time, we will be on the upper end, but if they are delayed, we've factored that into the lower end of our guidance.

因此，如果這些企業能夠按時獲得許可和註冊，我們的預期將處於較高水平，但如果它們被延遲，我們就會將其計入預期的較低水平。

Simon Baker, Redburn.

西蒙貝克，雷德伯恩。

There's also a clarification, Jamey.

還有一個澄清，傑米。

You mentioned the spend on respiratory trials being 50%.

您提到呼吸道試驗的花費佔了 50%。

Was that 50% of your total trial spend or 50% of your R&D spend?

這是您總試驗支出的 50% 還是研發支出的 50%？

And then just another question on the flu COVID combo following off from Jessica's question.

接著傑西卡的問題，還有另一個關於流感與 COVID 組合的問題。

I'm just interested in what the mechanism is and the timing at which point the regulators could ask for an extra data.

我只是想知道機制是什麼，以及監管機構什麼時候會要求額外數據。

Is this something that could come at any time?

這是隨時可能發生的事嗎？

If it happens sooner rather than later, do you think it would have an impact on the approval time line?

如果這件事發生得早，你認為這會對審批時間產生影響嗎？

And is there any risk in the US that the initial filing gets a complete response and then you have to refile with that COVID data.

在美國，是否存在這樣的風險：初次提交的申請得到了完整的回复，然後您必須使用該 COVID 數據重新提交？

Any color on the machinations, that would be very handy.

任何顏色的機械裝置都會非常方便。

Yes.

是的。

Thanks, Simon.

謝謝，西蒙。

On the first one, I was referencing 50% of the trial expense, which is what we break down in our 10-K.

對於第一個問題，我提到了 50% 的試驗費用，這是我們在 10-K 中細分的費用。

There are other line items that hit R&D in terms of the overhead that supports it, people, the sites, et cetera, or manufacturing facilities as well as research, but the 50% that I was referencing is really trial related, but you could imagine many of those other costs are also related, therefore, to the respiratory trials as well.

還有其他項目會影響研發，包括支援研發的間接費用、人員、場地等，或製造設施和研究，但我提到的 50% 實際上與試驗有關，但你可以想像，許多其他成本也與呼吸試驗有關。

Yes.

是的。

Thank you.

謝謝。

And so for the clarifying question, again, we have filed in multiple geographies, and I won't comment on individual regulatory exchanges.

因此，對於澄清問題，我們再次表示，我們已經在多個地區提交了申請，我不會對單獨的監管交易所發表評論。

But generally speaking, we -- as a part of the initial round of questions and feedback that we're receiving, there are instances where we think we will be dependent upon that efficacy data from the 1010 study, which we do expect in the coming months, the current season to be available.

但一般來說，作為我們收到的首輪問題和回饋的一部分，在某些情況下，我們認為我們將依賴 1010 研究的功效數據，我們預計這些數據將在未來幾個月內（當季）提供。

The timing of that readout and the impact on the review process for regulators is not something I can predict at this point, but we're in active discussion with regulators about it.

目前我還無法預測該報告的時間以及對監管機構審查過程的影響，但我們正在與監管機構積極討論此事。

Certainly, it is possible that if that is substantially delayed or if it is not a favorable efficacy readout, that it could, for sure, delay or impact the time line of approval for the combination product.

當然，如果療效數據嚴重延遲或不太理想，那麼肯定會延遲或影響組合產品的批准時間表。

If we are able to complete that submission, get that data to regulators and they're able to conduct their review, it's possible that we continue with that review without substantial delays.

如果我們能夠完成提交，將資料提交給監管機構，並且他們能夠進行審查，那麼我們就有可能繼續進行審查而不會出現重大延誤。

Ultimately, we don't know at this point because it will depend upon those submissions and discussions with the regulators that we're having right now.

最終，我們目前還不知道，因為這將取決於我們目前正在與監管機構進行的提交和討論。

But we did want to flag that we do think, based on some of the initial conversations that we may be dependent upon that data ultimately for approval with some in some geographies.

但我們確實想指出，根據一些初步對話，我們確實認為我們最終可能會依賴這些數據來獲得某些地區的批准。

Myles Minter, William Blair.

邁爾斯·明特、威廉·布萊爾。

Just one on potential ACIP recommendation review for RSV vaccines.

僅一項關於 RSV 疫苗潛在 ACIP 推薦審查。

Do you expect that hearing to be in February or the June meeting?

您預計聽證會將在二月還是六月舉行？

And is there anything built into the top end of that $2.5 billion revenue guidance for mRESVIA that would require a widening of that recommendation that it currently stands?

mRESVIA 25 億美元收入預期的最高值中是否有任何內容需要擴大目前的建議？

So I'll take the first question on timing.

因此我將回答關於時間的第一個問題。

We are obviously working closely with public health officials on the widening we filed for approval for the 18 to 59 high-risk population.

顯然，我們正在與公共衛生官員密切合作，爭取將疫苗覆蓋範圍擴大到 18 至 59 歲高風險族群。

At this point, we are not yet approved.

目前，我們尚未獲得批准。

And so from a broader sort of engagement with ACIP perspective, we'll wait for approval before we do that too broadly.

因此，從與 ACIP 更廣泛接觸的角度來看，我們會等待批准，然後再進行大規模的行動。

We do expect that the benefit risk is favorable for RSV vaccines, including mRESVIA.

我們確實預期 RSV 疫苗（包括 mRESVIA）的效益風險是有利的。

And so we do look forward to expansion of the recommendation to cover high-risk populations, both the 50 to 59, which have previously been discussed, but ultimately, hopefully 18-plus high-risk populations.

因此，我們確實期待擴大建議範圍，以涵蓋高風險族群，包括先前討論過的 50 至 59 歲族群，但最終希望涵蓋 18 歲以上的高風險族群。

And Jamey, I don't know if you take

Jamey，我不知道你是否接受

--

--

Yes.

是的。

Sure.

當然。

Yes.

是的。

So Myles, as I mentioned in Jess' question, we have a little bit of growth in RSV.

所以 Myles，正如我在 Jess 的問題中提到的那樣，我們的 RSV 取得了一些成長。

But I also mentioned that we have nothing related to new product approvals in our guidance for 2025.

但我也提到，我們的 2025 年指引中沒有任何與新產品核准相關的內容。

So that doesn't include the next-gen COVID vaccine or what Stephen just talked about, about the expanded indication related to RSV or anything from a combination approval should it happen.

因此，這不包括下一代 COVID 疫苗，也不包括史蒂芬剛才談到的與 RSV 相關的擴大適應症，或任何可能出現的聯合批准。

Tim Anderson, Bank of America.

美國銀行的蒂姆·安德森。

So if I could just go back to that very last point, on your 2022 revenue guidance, you're not including any new products.

因此，如果我可以回到最後一點，關於您的 2022 年收入預測，您沒有包括任何新產品。

Makes sense for RSV because that would be tiny.

對 RSV 來說這是有意義的，因為它很小。

Makes sense for the combo product because of the reasons that you outlined.

由於您所概述的原因，這對於組合產品來說是有意義的。

But why wouldn't the next-gen COVID product be included in guidance at this point, given that the PDUFA date is not very far away, end of May.

但是，考慮到 PDUFA 日期已經不遠了（5 月底），為什麼現在不將下一代 COVID 產品納入指導呢？

It's well-characterized paradigm having COVID vaccines out there.

目前已經有 COVID 疫苗，這是一個典型的範例。

I'm just wondering if that lack of inclusion guidance anticipates some uncertainty about approval, given the new administration coming in and this common thread of kind of an anti-COVID stance across lots of people from the Trump administration.

我只是想知道，考慮到新政府即將上台，以及川普政府中許多人都採取反新冠立場，缺乏包容性指導是否預示著批准方面會出現一些不確定性。

And then second question, on Norovirus.

第二個問題是關於諾羅病毒的。

If you're fully enrolled, what does FDA gain by putting the program on clinical hold?

如果您已經完全報名，那麼 FDA 將該計劃暫停臨床研究會為您帶來什麼好處？

Is that just a forced disclosure of that adverse event to the clinical and patient community?

這是否只是強制向臨床和患者群體披露該不良事件？

Or is there some other reason why they would do this?

或者他們這樣做有其他原因嗎？

Yes, Tim, thanks for the question.

是的，提姆，謝謝你的提問。

Maybe I'll take the first one.

也許我會選擇第一個。

So I don't think there's much to read into here.

因此我認為這裡沒什麼好解讀的。

I think we've learned our lesson coming into 2024 in terms of guiding with a product that is yet to be approved.

我認為，我們在 2024 年使用尚未獲得批准的產品進行指導方面已經吸取了教訓。

So moving forward, we have eliminated any products.

因此，今後我們將淘汰所有產品。

Of course, there could be upside.

當然，也可能存在好處。

But I think we approach our guidance understanding that there is variability and therefore, we will not put the any revenue related to the next-gen COVID or any of the other twoproducts as well.

但我認為，我們在製定指導方針時認識到存在可變性，因此，我們不會將任何與下​​一代 COVID 或任何其他兩種產品相關的收入納入其中。

And again, I don't think there's anything else to read into as a result of that.

而且我再說一遍，我不認為這還有什麼好解讀的。

Yes.

是的。

So on the question of Norovirus.

關於諾羅病毒的問題。

So importantly, we have already proactively communicated around this to all the investigators and IRBs and regulators around the world.

因此，重要的是，我們已經主動與世界各地的所有研究人員、IRB 和監管機構溝通了這種情況。

So that communications happened.

這樣溝通就實現了。

And actually, we've updated all the documents that would be necessary to sort of broadly identify this.

實際上，我們已經更新了所有必要的文件，以便廣泛地識別這一點。

So the purpose for the clinical hold, ultimately, have -- anticipate or asked the FDA that question.

因此，臨床暫停的目的最終是預期或向 FDA 提出這個問題。

I mean, at this point, they're appropriately, and we think prudently and conservatively, reviewing the documents and making sure that all their questions are answered around this.

我的意思是，此時，他們正在適當地（而且我們會謹慎而保守地考慮）審查文件並確保所有問題都得到解答。

It does not impact from our perspective right now in the Northern Hemisphere of study conduct.

從目前我們的角度來看，它不會對北半球的研究行為產生影響。

And so we'll look forward to engaging with them answering those questions, hopefully completing that review, removing that hole.

因此，我們期待與他們合作回答這些問題，希望完成審查，消除漏洞。

But as we said, we will not then reinitiate any enrollment because we now have 20,000 participants in the Northern Hemisphere, which is more than we feel like we need.

但正如我們所說的，我們不會重新開始任何招生，因為我們現在在北半球有 20,000 名參與者，這超出了我們的需求。

And so we'll just answer those questions and look for.

因此我們只需回答這些問題並尋找。

But I really couldn't offer any other insight around it, but it certainly isn't around transparency communication because that will happen proactively.

但我真的無法提供任何其他見解，但它肯定不是圍繞透明度溝通，因為這將主動發生。

We did that before -- as we submitted all the information to them and others.

我們以前就是這樣做的——我們將所有資訊提交給他們和其他人。

Ladies and gentlemen, this does conclude the Q&A portion of today's conference.

女士們、先生們，今天會議的問答部分到此結束。

I'd like to turn the call back to Stephane for any closing remarks.

我想將電話轉回給史蒂芬，請他做最後發言。

Thank you very much, everybody, for joining us and for your good questions.

非常感謝大家參加我們的活動並提出很好的問題。

Have a great day, and we look forward to speaking to some of you in the next hours and in the next days.

祝您有美好的一天，我們期待在接下來的幾個小時和幾天與你們交談。

Bye.

再見。

Ladies and gentlemen, this does conclude today's presentation.

女士們、先生們，今天的演講到此結束。

You may now disconnect, and have a wonderful day.

現在您可以斷開連接並享受美好的一天。