默克藥廠 (MRK) 2024 Q1 法說會逐字稿

Thank you for standing by. Welcome to the Merck & Co. Q1 Sales and Earnings Conference Call. (Operator Instructions) This call is being recorded. If you have any objections, you may disconnect at this time.

感謝您的支持。歡迎參加默克公司第一季銷售和收益電話會議。 （操作員指示）此通話正在錄音。如果您有任何異議，此時您可以斷開連接。

I would now like to turn the call over to Mr. Peter Dannenbaum, Senior Vice President, Investor Relations. Sir, you may begin.

現在，我想將電話轉給投資者關係資深副總裁 Peter Dannenbaum 先生。先生，您可以開始啦。

Thank you, Shirley, and good morning, everyone. Welcome to Merck's First Quarter 2024 Conference Call. Speaking on today's call will be Rob Davis, Chairman and Chief Executive Officer; Caroline Litchfield, Chief Financial Officer; and Dr. Dean Li, President of Merck Research Labs.

謝謝你，雪莉，大家早安。歡迎參加默克 2024 年第一季電話會議。今天的電話會議發言者將是董事長兼執行長羅布戴維斯 (Rob Davis)；卡洛琳‧利奇菲爾德 (Caroline Litchfield)，財務長；以及默克研究實驗室總裁 Dean Li 博士。

Before we get started, I'd like to point out a few items. You will see that we have items in our GAAP results, such as acquisition-related charges, restructuring costs and certain other items. You should note that we have excluded these from our non-GAAP results and provide a reconciliation in our press release.

在我們開始之前，我想指出幾點。您會看到，我們的 GAAP 結果包含一些項目，例如收購相關費用、重組成本和某些其他項目。您應該注意到，我們已將這些內容排除在我們的非公認會計準則結果之外，並在我們的新聞稿中提供了對帳。

I would like to remind you that some of the statements that we make today may be considered forward-looking statements within the meaning of the safe harbor provision of the U.S. Private Securities Litigation Reform Act of 1995. Such statements are made based on the current beliefs of Merck's management and are subject to significant risks and uncertainties. If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

我想提醒您，我們今天所做的一些聲明可能被視為美國 1995 年私人證券訴訟改革法案安全港條款所定義的前瞻性聲明。如果我們的基本假設被證明不準確或存在不確定性，實際結果可能與前瞻性陳述中的結果有重大差異。

Our SEC filings, including Item 1A and the 2023 10-K, identify certain risk factors and cautionary statements that could cause the company's actual results to differ materially from those projected in any of our forward-looking statements made this morning. Merck undertakes no obligation to publicly update any forward-looking statements.

我們的 SEC 文件（包括第 1A 項和 2023 年 10-K 表）確定了某些風險因素和警告聲明，這些因素和警告聲明可能導致公司的實際結果與我們今天上午做出的任何前瞻性聲明中的預測存在重大差異。默克不承擔公開更新任何前瞻性聲明的義務。

During today's call, a slide presentation will accompany our speakers' prepared remarks. These slides, along with our earnings release, today's prepared remarks and our SEC filings, are all posted to the Investor Relations section of Merck's website.

在今天的電話會議中，我們的發言人將以幻燈片形式演示其準備好的發言。這些投影片，連同我們的收益報告、今天的準備好的發言稿和我們的美國證券交易委員會文件，都發佈在默克網站的投資者關係部分。

With that, I'd like to turn the call over to Rob.

說完這些，我想把電話轉給 Rob。

Thanks, Peter. Good morning, and thank you for joining today's call. We've begun 2024 with continuing momentum in our business. We're harnessing the power of innovation to advance our deep pipeline and are maximizing the impact of our broad commercial portfolio for the benefit of patients. We drove strong growth across key therapeutic areas, executed strategic business development and are now launching a significant new product in the cardiometabolic space while also preparing for the potential approval and launch of 2 additional important candidates in vaccines in oncology. We have significant opportunities ahead of us across all areas of our business, and we're highly focused on realizing them.

謝謝，彼得。早安，感謝您參加今天的電話會議。進入 2024 年，我們的業務繼續保持良好發展勢頭。我們正在利用創新的力量來推進我們的深度產品線，並最大限度地發揮我們廣泛的商業組合的影響，使患者受益。我們在關鍵治療領域實現了強勁成長，實施了策略性業務發展，目前正在心臟代謝領域推出一款重要的新產品，同時也為另外兩種重要的腫瘤疫苗候選藥物的批准和上市做準備。我們在所有業務領域都面臨重大機遇，我們高度專注於實現這些機會。

I continue to be inspired by the dedication of our talented global team, which is working tirelessly to bring differentiated medicines and vaccines to patients through seamless scientific, commercial and operational execution. In March, we received FDA approval for WINREVAIR, a first-in-class treatment for adults with pulmonary arterial hypertension, a rare progressive and ultimately life-threatening disease. This marks the achievement of a significant milestone for our company. It exemplifies the value of our strategic priorities and demonstrates how our enduring commitment to our purpose is resulting in tangible benefits for patients.

我繼續受到我們才華橫溢的全球團隊的奉獻精神的啟發，他們正不懈地努力透過無縫的科學、商業和營運執行為患者提供差異化的藥物和疫苗。今年 3 月，我們獲得了 FDA 批准的 WINREVAIR，這是針對成人肺動脈高壓（一種罕見的進行性且最終危及生命的疾病）的首創治療藥物。這標誌著我們公司取得了一個重要的里程碑。它體現了我們策略重點的價值，並表明我們對目標的持久承諾如何為患者帶來實際的利益。

Just over 2 years since adding WINREVAIR to our pipeline, our attention now turns to the execution of a strong commercial launch where we have already seen prescriptions being written. We see a tremendous opportunity to positively impact the lives of people living with PAH. And further, the importance of this therapy to patients provides us with increased confidence in our ability to deliver sustainable long-term value for our shareholders. Strategic business development focused on the best external science remains an important priority for our company. We've demonstrated that we can leverage our deep discovery prowess to identify important acquisition targets and then add significant value through our powerful clinical research engine, our regulatory expertise and our commercial scale, which together can serve to accelerate development and enable broad global access to important medical discoveries for patients in need.

自從 WINREVAIR 加入我們的產品線以來僅僅兩年多的時間，我們現在將注意力轉向執行強有力的商業發布，我們已經看到了處方的開出。我們看到了對肺動脈高壓患者的生活產生積極影響的巨大機會。此外，這種療法對患者的重要性使我們對為股東提供可持續的長期價值的能力更有信心。專注於最佳外部科學的策略性業務發展仍然是我們公司的重要重點。我們已經證明，我們可以利用我們深厚的發現實力來確定重要的收購目標，然後透過我們強大的臨床研究引擎、我們的監管專業知識和我們的商業規模增加顯著的價值，這些可以共同加速發展，並使有需要的患者能夠在全球範圍內廣泛獲得重要的醫學發現。

Turning to our first quarter results. We achieved strong growth, reflecting robust demand for our innovative portfolio. We're pleased to reflect this momentum in our updated full year guidance, which Caroline will speak to in a moment. Turning to our broader research efforts. We're focused on advancing our expansive and diverse pipeline of leading-edge programs for the benefit of patients. In vaccines, we continue to pioneer new approaches to optimize disease prevention. In HPV, we're building on the foundation set by GARDASIL to further reduce the global burden of certain HPV-related cancers and disease by potentially providing broader protection with a new multivalent HPV vaccine and by generating data to clearly demonstrate whether or not a single dose of GARDASIL-9 provides comparable long-term protection to the approved 3-dose regimen in males and females ages 16 to 26.

談談我們的第一季業績。我們實現了強勁的成長，反映出對我們創新產品組合的強勁需求。我們很高興在更新的全年指引中反映出這一勢頭，卡羅琳稍後將會談到這一點。轉向我們更廣泛的研究努力。我們致力於推動廣泛而多樣化的前沿項目，以造福患者。在疫苗方面，我們不斷開拓新方法來優化疾病預防。在 HPV 方面，我們正在以 GARDASIL 奠定的基礎為基礎，透過新的多價 HPV 疫苗提供更廣泛的保護，並透過產生數據清楚地證明單劑量 GARDASIL-9 是否為 16 至 26 歲男性和女性提供與已批准的 3 劑量方案相當的長期保護，從而進一步減輕 HPV 相關癌症和疾病的全球負擔。

In pneumococcal, we presented additional compelling data for V116, a vaccine that is specifically designed to help protect against the majority of invasive pneumococcal disease in adults ages 65 and older and look forward to its potential approval in June. Each of these programs are platforms where we can provide meaningful protection to broad populations on a global scale. In HIV, in partnership with Gilead, we shared promising data from our revitalized program for a once-weekly combination of islatravir and lenacapavir in the treatment setting. We're actively progressing our comprehensive clinical program, which is focused on both treatment and prevention strategies to meet the evolving needs of the HIV community.

在肺炎球菌方面，我們提供了 V116 的更多令人信服的數據，V116 是一種專門設計用於幫助預防 65 歲及以上成年人大多數侵襲性肺炎球菌疾病的疫苗，我們期待它在六月獲得批准。每個專案都是我們可以為全球廣大民眾提供有效保護的平台。在愛滋病毒治療方面，我們與吉利德合作，分享了我們振興計劃的有希望的數據，該計劃在治療環境中每週使用一次伊拉曲韋和利那帕韋的組合。我們正在積極推進我們的綜合臨床計劃，該計劃專注於治療和預防策略，以滿足愛滋病毒社區不斷變化的需求。

And in oncology, we initiated several late-stage programs of novel candidates from our diverse pipeline as we work to expand our impact for patients and reinforce our leadership position over the long term. Finally, across our deep pipeline, we have significant clinical momentum in a range of therapeutic areas. Cutting-edge science is at the core of who we are, and I'm confident that Merck is well positioned to deliver the next wave of important innovations and value to patients, shareholders and to all of our stakeholders.

在腫瘤學領域，我們從多元化的候選藥物產品線中啟動了幾個後期項目，致力於擴大我們對患者的影響，並長期鞏固我們的領導地位。最後，在我們深度研發管線中，我們在一系列治療領域取得了顯著的臨床進展。尖端科學是我們的核心，我相信默克已經做好準備，為病人、股東和所有利害關係人帶來下一波重要的創新和價值。

In summary, our science-led strategy is delivering compelling proof points that we are creating a sustainable innovation engine that with continued clinical success will lead to a more diversified portfolio of growth drivers over the next decade and beyond. I again want to recognize the enormous efforts across our global organization. My confidence is strong and growing, that we are well positioned to build on this momentum and drive patient impact and value creation this year and well into the future. With that, I'll turn the call over to Caroline.

總而言之，我們以科學為主導的策略正在提供令人信服的證據，證明我們正在創建一個可持續的創新引擎，隨著臨床的持續成功，它將在未來十年及以後帶來更加多樣化的成長動力組合。我要再次讚揚我們全球組織所做的巨大努力。我的信心越來越強烈，我相信我們有能力利用這一勢頭，在今年乃至未來推動患者影響力和價值創造。說完這些，我會把電話轉給卡洛琳。

Thank you, Rob. Good morning. As Rob noted, we have had a strong start to the year with robust growth across our business, which reinforces the confidence we have in our outlook. We are also making strategic investments to leverage leading-edge science to save and improve lives around the world, positioning us to continue to deliver long-term value for patients, customers and shareholders. Now turning to our first quarter results. Total company revenues were $15.8 billion, an increase of 9% or 12% excluding the impact of foreign exchange. The impact from exchange is primarily driven by the devaluation of the Argentine peso, which was largely offset by inflation-related price increases consistent with market practice.

謝謝你，羅布。早安.正如 Rob 所說，我們今年開局良好，業務強勁成長，這增強了我們對未來前景的信心。我們也進行策略性投資，利用尖端科學來拯救和改善世界各地的生命，使我們能夠繼續為患者、客戶和股東提供長期價值。現在來談談我們的第一季業績。公司總營收為 158 億美元，成長 9%，若不考慮外匯影響則成長 12%。匯率的影響主要由於阿根廷比索貶值，但這一影響很大程度上被符合市場慣例的通膨相關價格上漲所抵消。

The following revenue comments will be on an ex-exchange basis. Our human health business continued its momentum with double-digit growth of 13%, driven by oncology and vaccines. Sales in our Animal Health business increased 4% across both companion animal and livestock products. Turning to the performance of our key brands. In oncology, sales of KEYTRUDA grew 24% to $6.9 billion, driven by increased uptake from earlier-stage cancers and continued strong demand from metastatic indications. In the U.S., KEYTRUDA grew across a broad range of tumors. In earlier-stage cancers, the increase was largely attributable to non-small cell lung cancer following the launches of KEYNOTE-671 and KEYNOTE-091.

以下收入評論將以交易所為基礎。在腫瘤學和疫苗的推動下，我們的人類健康業務繼續保持良好勢頭，實現 13% 的兩位數成長。我們的動物保健業務（包括伴侶動物和牲畜產品）的銷售額成長了 4%。談談我們主要品牌的表現。在腫瘤學領域，KEYTRUDA 的銷售額成長了 24%，達到 69 億美元，這得益於早期癌症的吸收增加以及轉移性適應症的持續強勁需求。在美國，KEYTRUDA 在多種腫瘤中均有生長。在早期癌症中，這種增長主要歸因於 KEYNOTE-671 和 KEYNOTE-091 推出後的非小細胞肺癌。

In the metastatic setting, we saw strong uptake from the recent launch of KEYNOTE A39 in first-line advanced urothelial cancer. Outside the U.S., KEYTRUDA growth was driven by continued uptake in earlier stage cancers, including high-risk early-stage triple-negative breast cancer and renal cell carcinoma as well as continued strong demand from patients with metastatic disease. Inflation-related price increases consistent with market practice in Argentina also contributed to growth. Alliance revenue from Lynparza and Lenvima grew 7% and 10%, respectively. WELIREG sales more than doubled to $85 million, driven by the additional indication following FDA approval of LITESPARK-005 for certain patients with previously treated advanced renal cell carcinoma as well as by increased uptake in certain VHL disease-associated tumors.

在轉移性治療方面，我們看到最近推出的 KEYNOTE A39 在第一線晚期尿路上皮癌治療的強勁成長。在美國以外，KEYTRUDA 的成長主要得益於早期癌症的持續成長，包括高風險早期三陰性乳癌和腎細胞癌，以及轉移性疾病患者的持續強勁需求。與阿根廷市場慣例相符的通貨膨脹相關價格上漲也促進了成長。來自 Lynparza 和 Lenvima 的聯盟收入分別成長了 7% 和 10%。 WELIREG 的銷售額增長了一倍多，達到 8500 萬美元，這得益於 FDA 批准 LITESPARK-005 用於治療某些先前接受過治療的晚期腎細胞癌患者後的額外適應症，以及某些 VHL 疾病相關腫瘤的吸收增加。

Our vaccines portfolio delivered strong growth, led by GARDASIL, which increased 17% to $2.2 billion, driven by global demand. Sales also benefited from the timing of shipments in China and CDC purchasing patterns in the U.S. VAXNEUVANCE sales grew to $219 million, driven by continued uptake of the pediatric indication in the U.S. and ongoing launches in international markets, particularly in Europe. In the U.S., VAXNEUVANCE sales also benefited from CDC purchasing patterns. Sales in our Animal Health business grew 4%. Livestock sales growth was driven by price actions as well as demand for swine and poultry products. Companion animal growth reflects price actions.

我們的疫苗組合實現強勁成長，其中 GARDASIL 成長最為顯著，受全球需求推動，其銷售額成長 17%，達到 22 億美元。銷售額也受益於中國出貨時間和美國 CDC 的採購模式。在美國，VAXNEUVANCE的銷售也受惠於CDC的採購模式。我們的動物保健業務銷售額成長了 4%。牲畜銷售成長受到價格走勢以及對豬肉和家禽產品的需求所推動。伴侶動物的成長反映了價格行為。

I will now walk you through the remainder of our P&L, and my comments will be on a non-GAAP basis. Gross margin was 81.2%, an increase of 4.3 percentage points driven by reduced royalty rates for KEYTRUDA and GARDASIL, which went into effect at the beginning of this year as well as favorable product mix. Operating expenses decreased 4% to $6.4 billion, a charge of $656 million related to the acquisition of Harpoon Therapeutics this quarter was lower than the $1.4 billion of charges a year ago for certain business development transactions. Excluding these charges, operating expenses grew 8%.

現在我將向您介紹我們損益表的剩餘部分，我的評論將基於非 GAAP 基礎。毛利率為 81.2%，成長 4.3 個百分點，主要得益於今年年初生效的 KEYTRUDA 和 GARDASIL 專利費率降低以及有利的產品組合。營業費用下降 4% 至 64 億美元，本季與收購 Harpoon Therapeutics 相關的 6.56 億美元費用低於去年同期因某些業務發展交易而產生的 14 億美元費用。除去這些費用，營業費用增加了 8%。

We remain committed to investing appropriately to realize the promise of our expensive early and late phase pipeline and support the promotion of our key growth drivers. Other expense was $87 million. Our tax rate was 16.1%, including the impact from the Harpoon transaction for which no tax benefit was recorded. Taken together, earnings per share were $2.07, which includes a $0.26 negative impact from the charge related to Harpoon.

我們將繼續致力於適當投資，以實現我們昂貴的早期和後期產品線的承諾，並支持促進我們的關鍵成長動力。其他費用為8700萬美元。我們的稅率為 16.1%，其中包括 Harpoon 交易的影響，該交易未記錄任何稅收優惠。總體來看，每股收益為 2.07 美元，其中包括與 Harpoon 相關費用產生的 0.26 美元負面影響。

Now turning to our 2024 non-GAAP guidance. The operational strength of our business has enabled us to raise and narrow our full year revenue guidance. We now expect revenue to be between $63.1 million and $64.3 billion, reflecting strong year-over-year revenue growth of 5% to 7%, including the negative impact from foreign exchange. At the midpoint of this range, operational strength in our business of approximately $600 million is partially offset by an incremental headwind from foreign exchange of approximately $400 million using mid-April rates resulting in a full year negative impact from foreign exchange of approximately 3%.

現在來談談我們的 2024 年非 GAAP 指引。我們業務的營運實力使我們能夠提高和縮小全年收入預期。我們現在預計營收在 6,310 萬美元至 643 億美元之間，反映出 5% 至 7% 的強勁年收入成長，其中包括外匯帶來的負面影響。在這個範圍的中間點，我們業務中約 6 億美元的營運實力被以 4 月中旬匯率計算的約 4 億美元外匯增量逆風部分抵消，導致全年外匯負面影響約為 3%。

Our gross margin assumption is now expected to be approximately 81%. Our estimated range of operating expenses is between $25.2 million and $26.1 billion, which does not assume additional significant potential business development transactions. Other expense is expected to be approximately $250 million. Our full year tax rate is unchanged between 14.5% and 15.5%. We assume approximately 2.55 billion shares outstanding. Taken together, we are increasing and narrowing our expected EPS range to $8.53 to $8.65. This is a $0.07 increase at the midpoint despite an incremental headwind from foreign exchange of approximately $0.05 using mid-April rates, resulting in a full year negative impact from foreign exchange of more than $0.30.

我們現在預計毛利率約為81%。我們預計的營運費用範圍在 2,520 萬美元至 261 億美元之間，其中不包括額外的重大潛在業務發展交易。其他費用預計約2.5億美元。我們的全年稅率維持不變，介於14.5%至15.5%之間。我們估計流通股數約為 25.5 億股。綜合起來，我們將預期每股收益範圍上調並縮小至 8.53 美元至 8.65 美元。儘管以 4 月中旬的匯率計算，外匯帶來的增量阻力約為 0.05 美元，但按中點計算，這一數字仍增加了 0.07 美元，導致全年外匯帶來超過 0.30 美元的負面影響。

As you consider your models, there are a few items to keep in mind. The increase in our sales guidance is driven by the strong performance across our current product portfolio, led by KEYTRUDA, which continues to experience growth from additional indications and patient demand. For GARDASIL, second quarter ex U.S. growth will be adversely impacted by shipment timing to China. This year, we expect more evenly distributed quarterly shipments to China. Recall, in 2023, we accelerated shipments from the second half to the first half of the year, which primarily impacted the second quarter. Over the near and long term, we remain confident in our ability to protect many more people from HPV-related cancers and drive growth of GARDASIL.

當你考慮你的模型時，有幾點需要牢記。我們銷售預期的增加得益於我們目前產品組合的強勁表現，其中以 KEYTRUDA 為首，該產品組合因新增適應症和患者需求而持續增長。對於 GARDASIL 而言，第二季度美國以外地區的成長將受到運往中國的時機的不利影響。今年，我們預計對中國的季度出貨量分佈將更加均勻。回想一下，2023 年，我們將出貨量從下半年加速到上半年，主要影響了第二季。從短期和長期來看，我們仍然有信心保護更多人免受 HPV 相關癌症的侵害並推動 GARDASIL 的發展。

Sales of LAGEVRIO in the first quarter were driven by an extended wave of COVID-19 in Asia Pacific markets. LAGEVRIO continues to be an important treatment option for certain patients with COVID-19. So we continue to anticipate full year sales to be lower than last year. We are excited to provide a novel treatment option for adult patients with pulmonary arterial hypertension, following the recent FDA approval of WINREVAIR. We are seeing high interest from patient groups and a range of relevant prescribers. We are also making good progress in enabling access.

LAGEVRIO 第一季的銷售受到亞太市場新冠疫情蔓延的推動。對於某些 COVID-19 患者來說，LAGEVRIO 仍然是重要的治療選擇。因此，我們繼續預計全年銷售額將低於去年。繼 FDA 最近批准 WINREVAIR 之後，我們很高興為成年肺動脈高壓患者提供新的治療選擇。我們看到患者群體和一系列相關處方人員表現出濃厚的興趣。我們在實現訪問方面也取得了良好的進展。

Several payers have already established coverage policies consistent with the label and STELLAR study criteria, while others are in the process of developing their policies. As we go forward, we intend to provide an appropriate level of transparency to enable insight into the impact we are having on patients, including prescription data and revenues. In summary, we are confident in a successful launch of WINREVAIR, consistent with our prior expectations and look forward to providing updates on our progress.

一些付款人已經制定了與標籤和 STELLAR 研究標準一致的承保政策，而其他付款人正在製定他們的政策。隨著我們前進，我們打算提供適當程度的透明度，以便深入了解我們對患者的影響，包括處方數據和收入。總之，我們對 WINREVAIR 的成功推出充滿信心，這與我們先前的預期一致，並期待提供有關我們進展的最新資訊。

Now turning to capital allocation, where our strategy remains unchanged. We will prioritize investments in our business to drive near- and long-term growth. We will continue to invest in our innovative pipeline, including the initiation of many new late-stage clinical trials across multiple novel candidates, each of which has the potential to meaningfully address important unmet medical needs. We remain committed to our dividend and plan to increase it over time. Adding compelling science to our pipeline through business development remains a high priority. We maintain ample capacity given our strong investment-grade credit rating and cash flow to pursue additional science-driven value-enhancing transactions. We will continue to execute a modest level of share repurchases.

現在轉向資本配置，我們的策略保持不變。我們將優先投資我們的業務，以推動近期和長期成長。我們將繼續投資我們的創新管道，包括啟動多個新型候選藥物的許多新的後期臨床試驗，每個候選藥物都有可能有效解決重要的未滿足的醫療需求。我們將繼續致力於派發股息，並計劃隨著時間的推移增加股息。透過業務開發為我們的管道增添引人注目的科學仍然是我們的首要任務。鑑於我們強大的投資等級信用評級和現金流，我們保持充足的產能來追求更多以科學為導向的增值交易。我們將繼續進行適度的股票回購。

To conclude, we remain confident in the near- and long-term outlook of our business, driven by the global demand for our innovative medicines and vaccines as well as our exceptional pipeline. Our unwavering commitment to use the power of cutting-edge science to improve the lives of the patients we serve has put us in a position of financial and operational strength. Our excellent execution and continued investments in innovation will enable us to deliver value to patients, customers and shareholders now and well into the future. With that, I'd now like to turn the call over to Dean.

總而言之，由於全球對我們的創新藥物和疫苗的需求以及我們卓越的產品線，我們對我們的業務的近期和長期前景仍然充滿信心。我們堅定不移地致力於利用尖端科學的力量來改善我們所服務的患者的生活，這使我們處於財務和營運實力的地位。我們出色的執行力和對創新的持續投資將使我們能夠現在和將來為患者、客戶和股東創造價值。說完這些，我現在想把電話轉給 Dean。

Thank you, Caroline. In the first quarter, we continued to make progress with a steady cadence of clinical regulatory milestones across our pipeline. Today, I will provide updates from our cardiometabolic disease portfolio, HIV and vaccine programs and close with advances in our oncology pipeline. As Rob and Caroline noted, late last month, we received approval from the FDA for WINREVAIR, our first-in-class active and signaling inhibitor for the treatment of dose living with pulmonary arterial hypertension to increase exercise capacity, improve WHO functional class and reduce the risk of clinical worsening events.

謝謝你，卡洛琳。第一季度，我們持續取得進展，整個研發過程中的臨床監管里程碑穩步推進。今天，我將介紹我們的心臟代謝疾病產品組合、愛滋病毒和疫苗計畫的最新進展，並最後介紹我們腫瘤學產品線的進展。正如 Rob 和 Caroline 所說，上個月底，我們獲得了 FDA 對 WINREVAIR 的批准，這是我們的首創活性和訊號抑制劑，用於治療患有肺動脈高壓的患者，以提高運動能力，改善 WHO 功能等級，並降低臨床惡化事件的風險。

WINREVAIR is a novel therapeutic option that targets a new PAH treatment pathway and is indicated to treat a broad PAH population. This approval marks a significant step towards our goal of transforming the treatment journey for many patients with PAH. WINREVAIR is currently being reviewed by the European Medicines Agency with a decision anticipated in the second half of this year. The Phase III ZENITH and Hyperion studies evaluating patients with more advanced disease and those earlier on in their disease journey, respectively, are ongoing as well as the Phase II cadence trial evaluating WHO Group II pulmonary hypertension, a type of left heart disease.

WINREVAIR 是一種新型治療選擇，針對新的 PAH 治療途徑，適用於治療廣泛的 PAH 族群。這項批准標誌著我們朝著改變眾多 PAH 患者治療歷程的目標邁出了重要一步。 WINREVAIR 目前正在接受歐洲藥品管理局的審查，預計將在今年下半年做出決定。目前正在進行的 III 期 ZENITH 和 Hyperion 研究分別對晚期患者和早期患者進行評估，同時正在進行 II 期節奏試驗，以評估世界衛生組織 II 組肺動脈高壓（一種左心疾病）。

Our commitment extends to a broad range of pulmonary hypertension, informed by results from the Phase II cohort of the Phase II/III insignia PAH study evaluating MK-5475, our inhaled soluble guanylate cyclase stimulator and the STELLAR trial results for WINREVAIR, we have made the decision to focus the development of MK-5475 on WHO Group 3.1 pulmonary hypertension associated with COPD, and not further proceed in PAH. PH-COPD is an area of significant need with no specific therapies currently approved. Our HIV pipeline continues to advance. Last month, presentations at the conference on retroviruses and opportunistic infections, reinforce progress in our strategy to develop less frequent dosing regimens for managing and treating HIV.

我們的承諾擴展到廣泛的肺動脈高壓，根據評估 MK-5475 的 II/III 期 insignia PAH 研究的 II 期隊列結果、我們的吸入式可溶性鳥苷酸環化酶刺激劑和 WINREVAIR 的 STELLAR 試驗結果，我們已決定將 MK-5475 的開發重點放在與 COPD 相關的肺 3.1 方面。 PH-COPD 是一個亟待解決的領域，目前尚無任何特定療法獲得批准。我們的愛滋病毒治療管道持續取得進展。上個月，逆轉錄病毒和機會性感染會議上的報告鞏固了我們在開髮用於管理和治療愛滋病毒的較低頻率給藥方案的策略方面取得的進展。

We believe these programs have the potential to help address adherence, stigma and other challenges faced by some individuals taking daily antiretroviral pills. In collaboration with Gilead, safety and efficacy findings were presented from a Phase II study evaluating a once-weekly oral combination of islatravir, an investigation on nucleoside reverse transcriptase translocation inhibitor and lenacapavir, a first-in-class capsid inhibitor for the treatment of adults living with HIV. At 24 weeks, the trial met its primary endpoint and in a secondary endpoint maintained a high rate of viral suppression. Additional longer-term data will be presented at a later date.

我們相信這些計畫有潛力幫助解決一些每天服用抗逆轉錄病毒藥物的人所面臨的依從性、恥辱感和其他挑戰。與吉利德合作，進行了一項 II 期研究，評估每週一次口服 islatravir 組合的安全性和有效性結果，islatravir 是一項關於核苷逆轉錄酶易位抑製劑和 lenacapavir 的研究，lenacapavir 是一種用於治療愛滋病毒感染者的首創衣殼抑制劑。在 24 週時，試驗達到了其主要終點，並在次要終點保持了較高的病毒抑制率。稍後將提供更多長期數據。

In addition, safety and tolerability data were presented for MK-8527 a novel oral NRTTI candidates from 2 Phase I trials that evaluated ascending single dose and multiple doses in adults 18 to 55 years old, not infected with HIV. MK-8527 is being investigated as a potential monthly option for HIV pre-exposure prophylaxis. Vaccines remain an important element of our pipeline, and we are making progress across several programs. Findings from multiple Phase III trials of V116, our investigational 21 valent pneumococcal conjugate vaccine were presented at the meeting of the International Society of pneumonia and Pneumococcal Diseases last month. V116 was shown to be immunogenic for all 21 serotypes covered by the vaccine, including a pneumococcal vaccine naive and vaccine experience adults as well as those at increased risk for pneumococcal disease. If approved, V116 would be the first vaccine specifically designed to address the majority of serotypes that cause invasive pneumococcal disease in adults, ages 65 and older.

此外，還提供了 MK-8527 的安全性和耐受性數據，MK-8527 是一種新型口服 NRTTI 候選藥物，來自兩項 I 期試驗，這兩項試驗評估了 18 至 55 歲未感染 HIV 的成年人中單劑量和多劑量遞增的效果。 MK-8527 正在被研究作為一種潛在的每月 HIV 暴露前預防治療方案。疫苗仍然是我們產品線的重要組成部分，我們在多個項目上都取得了進展。上個月，我們在國際肺炎和肺炎球菌疾病學會會議上公佈了我們正在研究的 21 價肺炎球菌結合疫苗 V116 的多項 III 期試驗結果。研究表明，V116 對疫苗涵蓋的​​所有 21 种血清型均具有免疫原性，包括未接種過肺炎球菌疫苗的成年人和接種過疫苗的成年人以及患肺炎球菌疾病風險較高的人群。如果獲得批准，V116 將成為第一個專門針對導致 65 歲及以上成人侵襲性肺炎球菌疾病的大多數血清型而設計的疫苗。

The target action date is June 17. The meeting of the CDC's Advisory Committee on immunization practices is scheduled shortly thereafter. Since the initial approval of GARDASIL, a steady flow of clinical and real-world evidence has been generated to support the favorable efficacy, effectiveness, safety and long-term durability of protection against certain human papillomavirus-related cancers and diseases in both males and females. Despite the proven public health benefit of HPV vaccination, the latest global cancer statistics from the International Agency for Research on Cancer indicate there is more to do to help increase vaccination rates.

目標行動日期是 6 月 17 日。自 GARDASIL 首次獲批以來，已有大量的臨床和現實世界證據支持該疫苗對男性和女性預防某些人類乳突病毒相關癌症和疾病具有良好的功效、效果、安全性和長期持久性。儘管 HPV 疫苗接種已被證明對公共衛生有益，但國際癌症研究機構的最新全球癌症統計數據表明，還需要採取更多措施來提高疫苗接種率。

The latest statistics from 2022 ranked cervical cancer as the fourth most common cancer globally in terms of incidents and mortality in women and the leading cause of cancer death in 37 countries, predominantly in sub-Saharan Africa, South America and Southeast Asia regions. At the Urogen Congress, last month, we disclosed plans to build on the development of GARDASIL with a new clinical program to identify a novel multivalent HPV vaccine candidate with the potential to extend protection against a broader array of HPV types. This includes several types known to disproportionately impact African and Asian populations and individuals of African and Asian descent. First-in-human studies are scheduled to start in the fourth quarter of this year.

2022 年的最新統計顯示，子宮頸癌是全球女性發病率和死亡率第四大常見癌症，也是 37 個國家癌症死亡的主要原因，主要在撒哈拉以南非洲、南美洲和東南亞地區。在上個月的泌尿外科大會上，我們披露了在 GARDASIL 開發基礎上開展新臨床計劃的計劃，該計劃旨在確定一種新型多價 HPV 候選疫苗，該疫苗有可能擴大對更廣泛 HPV 類型的保護。其中包括幾種已知對非洲和亞洲人口以及非洲和亞洲血統的個人造成不成比例影響的類型。首次人體研究預計今年第四季開始。

In addition, we announced plans to conduct 2 randomized, double-blind multiyear clinical trials in females and males ages 16 to 26 years to examine the short- and long-term efficacy and immunogenicity of a single dose of GARDASIL-9 versus the currently approved 3-dose regimen. The goal of these studies is to generate data that clearly demonstrates whether or not a single dose of GARDASIL-9 provides comparable long-term protection to the approved regimen, while also satisfying the high standards required by regulatory authorities. The clinical trials are anticipated to start enrolling in the fourth quarter.

此外，我們宣布計劃對 16 至 26 歲的女性和男性進行兩項隨機、雙盲多年臨床試驗，以檢驗單劑量 GARDASIL-9 與目前批准的 3 劑量方案的短期和長期療效和免疫原性。這些研究的目標是產生數據，清楚證明單劑量 GARDASIL-9 是否能提供與核准方案相當的長期保護，同時滿足監管機構要求的高標準。臨床試驗預計將於第四季開始招募。

In oncology, we continue to focus on our 3-pillared strategy comprised of immuno-oncology, precision molecular targeting and tissue targeting agents. In immuno-oncology, September 2024 will mark a decade since the first approval of KEYTRUDA in metastatic melanoma. KEYTRUDA has since amassed approvals for 39 indication and continues to reinforce its reputation as a foundational therapy for certain types of cancer. Building on the recent FDA approval for KEYTRUDA in combination with chemotherapy for the treatment of FIGO 2014, Stage II through IVA cervical cancer, we recently announced that the pivotal KEYNOTE-A18 trial met its primary endpoint of overall survival, potentially providing a new standard of care for these patients. Our commitment to providing better options to prevent and treat cervical cancer remain strong. Also, in women's cancer, the Phase III KEYNOTE-868 trial, known as NRG-GY018 was granted priority review by the FDA for the first-line treatment of patients with primary advanced or recurrent endometrial carcinoma. This agency has set a target action date of June 21.

在腫瘤學領域，我們繼續專注於由免疫腫瘤學、精準分子標靶和組織標靶藥物組成的三大支柱策略。在免疫腫瘤學領域，2024 年 9 月將是 KEYTRUDA 首次獲準用於治療轉移性黑色素瘤的十年。 KEYTRUDA 迄今已獲得 39 種適應症的批准，並繼續鞏固其作為某些類型癌症基礎療法的聲譽。基於 FDA 最近批准 KEYTRUDA 與化療聯合用於治療 FIGO 2014 II 期至 IVA 期子宮頸癌，我們最近宣布關鍵的 KEYNOTE-A18 試驗達到了總體生存期的主要終點，可能為這些患者提供新的治療標準。我們始終致力於提供更好的預防和治療子宮頸癌的選擇。此外，在女性癌症領域，第三階段 KEYNOTE-868 試驗（稱為 NRG-GY018）被 FDA 授予優先審查，用於原發性晚期或復發性子宮內膜癌患者的一線治療。該機構已將目標行動日期設定為 6 月 21 日。

Outside of the U.S., the European Commission approved KEYTRUDA in combination with platinum doublet chemotherapy as neoadjuvant therapy followed by adjuvant KEYTRUDA in adult patients with non-small cell lung cancer at high risk of recurrence based on the Phase III KEYNOTE-671 study. This marks the first approval in Europe for an anti-PD-1 PD-L1 therapy as part of a treatment regimen for the neoadjuvant followed by adjuvant treatment of resectable non-small cell lung cancer based on positive overall survival results.

在美國以外，歐盟委員會根據 III 期 KEYNOTE-671 研究批准 KEYTRUDA 合併鉑類雙藥化療作為新輔助治療，隨後對復發風險較高的非小細胞肺癌成年患者進行輔助 KEYTRUDA 治療。這標誌著歐洲首次批准抗 PD-1 PD-L1 療法作為可切除非小細胞肺癌新輔助治療方案的一部分，隨後基於陽性總體生存結果進行輔助治療。

Next to precision targeting. Building on the success of KEYTRUDA for certain patients with non-small cell lung cancer, earlier this month, we announced the initiation of the Phase III clinical trial for MK-1084, an investigational oral selective KRAS G12C inhibitor in combination with KEYTRUDA for the first-line treatment of certain patients with metastatic non-small cell lung cancer. The decision to proceed to Phase III was based upon early promising evidence from a Phase I study showing antitumor activity and a manageable safety profile. KRAS is one of the most prevalent oncogenes in human cancers, and G12C is the most common KRAS mutation in patients with non-small cell lung cancer.

接下來是精準瞄準。基於 KEYTRUDA 對某些非小細胞肺癌患者取得成功，本月初，我們宣布啟動 MK-1084 的 III 期臨床試驗，MK-1084 是一種在研口服選擇性 KRAS G12C 抑製劑，與 KEYTRUDA 聯合用於某些轉移性非小細胞肺癌患者的一線治療。進入第三階段的決定是基於第一階段研究的早期有希望的證據，該研究顯示了抗腫瘤活性和可控的安全性。 KRAS是人類癌症中最常見的致癌基因之一，G12C 是非小細胞肺癌患者中最常見的 KRAS 突變。

In the tissue targeting space, we are moving with speed and rigor to advance a broad pipeline of antibody drug conjugates with multiple planned and ongoing Phase III trials. In just over 6 months, we have made remarkable progress in our collaboration with Daiichi Sankyo. Recently, we announced that the first patient has been dosed in the Phase II/III REJOICE OVARIAN01 trial evaluating the efficacy and safety of raludotatug deruxtecan, an investigational CDH6 directed DXDADC in patients with platinum-resistant ovarian cancer. We are poised to begin a Phase III study evaluating ifinatamab/deruxtecan, a B7-H3-directed ADC in small cell lung cancer, a notably difficult-to-treat tumor type. New treatment options are desperately needed for these patients where the prognosis remains poor.

在組織靶向領域，我們正在快速而嚴格地推進廣泛的抗體藥物偶聯物產品線，並計劃進行和正在進行多個 III 期試驗。在短短6個多月的時間裡，我們與第一三共的合作取得了顯著進展。最近，我們宣布，II/III 期 REJOICE OVARIAN01 試驗的第一位患者已經接受給藥，該試驗評估了 raludotatug deruxtecan（一種針對鉑耐藥性卵巢癌患者的試驗性 CDH6 導引 DXDADC）的療效和安全性。我們準備開始一項 III 期研究，評估 ifinatamab/deruxtecan（一種針對 B7-H3 的 ADC，用於治療小細胞肺癌，一種特別難治療的腫瘤類型）。對於這些預後仍然不佳的患者，迫切需要新的治療選擇。

We are pleased to have recently completed the acquisition of Harpoon Therapeutics, which provides novel T cell engagers, including MK-6070, an investigational delta-like ligand 3 targeting T cell engager, also being evaluated in certain types of small cell lung cancer as well as neuroendocrine tumors.

我們很高興最近完成了對 Harpoon Therapeutics 的收購，該公司提供新型 T 細胞接合劑，包括 MK-6070，這是一種正在研究的 delta 樣配體 3 靶向 T 細胞接合劑，也正在對某些類型的小細胞肺癌以及神經內分泌腫瘤進行評估。

Finally, please mark your calendars for the evening of Monday, June 3, where we will host an investor event at ASCO in Chicago and provide an update on our diverse portfolio of immuno-oncology, precision molecular and tissue-targeting agents.

最後，請在您的日曆上標記 6 月 3 日星期一晚上，我們將在芝加哥的 ASCO 舉辦一場投資者活動，並提供有關我們多樣化的免疫腫瘤學、精準分子和組織靶向藥物產品組合的最新信息。

Looking forward, June promises to be a busy month with 3 regulatory action dates, including V116 for prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults. KEYTRUDA for primary advanced or recurrent endometrial carcinoma; and patritumab/deruxtecan for advanced EGFR-mutated non-small cell lung cancer.

展望未來，6 月將是一個繁忙的月份，有 3 個監管行動日期，包括用於預防成人侵襲性肺炎球菌疾病和肺炎球菌性肺炎的 V116。 KEYTRUDA 用於治療原發性晚期或復發性子宮內膜癌；以及 patritumab/deruxtecan，用於治療晚期 EGFR 突變的非小細胞肺癌。

We continue to execute on our strategy with a focus on operational excellence and look forward to providing further updates on our progress throughout the year.

我們將繼續執行我們的策略，專注於卓越運營，並期待全年進一步更新我們的進展。

And now I will turn the call back to Peter.

現在我將把電話轉回給彼得。

Thank you, Dean. Shirley, we're ready to begin Q&A. (Operator Instructions) Thank you.

謝謝你，迪恩。雪莉，我們準備開始問答環節。 （操作員指示）謝謝。

(Operator Instructions) Our first question comes from Terence Flynn with Morgan Stanley.

（操作員指示）我們的第一個問題來自摩根士丹利的 Terence Flynn。

This is probably one for Dean. Obviously, you guys have been focused on building out your cardiometabolic franchise now. You have the sotatercept launch underway. You've got an oral PCSK9 in late-stage development. You have a GLP glucagon also moving forward for NASH, I believe. But I guess I'd just be curious how you think about the opportunity in obesity broadly as, on one hand, it seems like it could align with your current footprint. But on the other hand, it seems like Merck has gone more towards specialty markets and away from kind of primary care. So maybe just would love your thoughts there, Dean, as you think about building out.

這可能就是 Dean 的風格。顯然，你們現在一直專注於打造心臟代謝特許經營權。您正在進行 sotatercept 的發布。您的口服 PCSK9 已進入後期開發階段。我相信，GLP 胰高血糖素也正在用於治療 NASH。但我想我只是好奇你如何廣泛地看待肥胖帶來的機會，一方面，它似乎與你目前的足跡一致。但另一方面，默克似乎更轉向了專業市場，而遠離了初級保健。所以也許我只是想知道你的想法，Dean，當你考慮建設時。

Well, thank you very much. Yes, we are excited about the build-out that we have in cardiovascular metabolic. You pointed out the programs that have the most visibility right now. But let me assure you, there will be other programs that you will have more visibility over the coming years.

好吧，非常感謝。是的，我們對心血管代謝的進步感到非常興奮。您指出了目前最受關注的項目。但我向你們保證，未來幾年還會有其他項目讓你們更重視。

In relationship to your question about GLP and obesity, I think there's 2 ways to look at it: you can look at it from a GLP angle, and you can look at it from an obesity angle. If you look at it from a GLP angle, there has been really important work showing its impact in diabetes, weight loss, more recently, in cardiovascular outcomes, most recently in sleep apnea.

關於您提到的 GLP 和肥胖的問題，我認為有兩種看法：可以從 GLP 角度來看，也可以從肥胖角度來看。如果從 GLP 的角度來看，已經有非常重要的研究表明其對糖尿病、減肥以及最近的心血管結果和睡眠呼吸中止症的影響。

And you're right, we're very interested in relationship to MASH. We think that's an also important outcome. And we also think that there will be distinct populations, whether you call it obese or whether you call it NASH or -- within that GLP space. With distinct populations, it will be important to give a benefit of a molecule that really takes care of the primary concern. And that's our play, for example, in NASH, where we think we have a very tolerable drug that has significant reduction in liver fat and also gives a weight loss of 10% to 12%.

你說得對，我們對與 MASH 的關係非常感興趣。我們認為這也是一個重要的結果。我們也認為，在 GLP 空間內，將會存在不同的人群，無論你稱之為肥胖或 NASH。對於不同的族群來說，提供真正解決主要問題的分子優勢非常重要。這就是我們的策略，例如，在 NASH 方面，我們認為我們有一種耐受性非常好的藥物，可以顯著減少肝臟脂肪，同時使體重減輕 10% 至 12%。

When you look at that, I think these different outcomes may need different molecules. More generally, if you're talking about obesity, I do think that there's important work going on right now. But I think that there could be another wave where people start thinking about orals, how tolerable they are, the accessibility they are, combinations, how do you maintain, how you preserve muscle and also additional outcomes. And it may not be that the same molecule is the best molecule that wins out in every one of those sub populations. And so I would just -- I wonder if there will be some fractionation of the patient population when you say the word, for example, generally, obesity. And we wonder if there's opportunity there.

當你看到這一點時，我認為這些不同的結果可能需要不同的分子。更普遍地說，如果你談論肥胖問題，我確實認為現在正在進行重要的工作。但我認為可能會出現另一波浪潮，人們開始考慮口服藥物，它們的耐受性如何，它們的可及性，組合使用，如何維持，如何保持肌肉以及其他結果。而且，可能並不是同一種分子就是在每個亞群中勝出的最佳分子。所以我只是——我想知道當你說出這個詞時，患者群體是否會出現某種分化，例如，一般來說，肥胖。我們想知道那裡是否有機會。

Our next question comes from Evan Seigerman with BMO Capital Markets.

下一個問題來自 BMO 資本市場的 Evan Seigerman。

I wanted to touch on some of your work in lung cancer, specifically with KRAS G12C, echoing Dean's comment. So this space is becoming increasingly crowded. Maybe walk me through what you believe differentiates your assets today from the currently approved one or from the pan-KRAS assets in development.

我想談談您在肺癌方面的一些研究，特別是關於 KRAS G12C 的研究，這與 Dean 的評論相呼應。所以這個空間變得越來越擁擠。也許您可以向我介紹一下您認為您目前的資產與目前批准的資產或正在開發的泛 KRAS 資產有何區別。

Yes. So this is one of my more favorite projects. So I appreciate that you actually ask a question about it. When you look at KRAS, as you point out, there is -- it's one of the most important driver mutations in multiple cancers. And if you say more broadly, not KRAS but pan-RAS, that is also true.

是的。這是我最喜歡的項目之一。因此我很感激您確實就此提出問題。正如您所指出的，當您觀察 KRAS 時，它是多種癌症中最重要的驅動突變之一。如果更廣泛地說，不是 KRAS 而是泛 RAS，那也是如此。

In relationship to KRAS G12C, that's a small percentage of all the KRAS mutations and all the RAS mutations. But where KRAS G12C is especially prominent is in non-small cell lung cancer. It's, depending on the percentage, 12% to 15% in that patient population.

與 KRAS G12C 相比，這只佔所有 KRAS 突變和所有 RAS 突變的一小部分。但 KRAS G12C 在非小細胞肺癌中尤為突出。這取決於患者群體的百分比，為 12% 至 15%。

And I will also emphasize that we have a lot of data in relationship to that patient population in non-small cell lung cancer. It's KEYNOTE-189. It's chemo plus IO. You need a potent compound with a KRAS to move it into first line. That's the game that we're trying to play. So it is crowded. But what you're looking for is a potent compound that has tremendous monotherapy efficacy. But most importantly, when you combine it with, for example, pembro, you maintain the dose, you maintain the ability to not have dose modifications. And that's the data that made us excited about this because I think we reported an ORR of 71% in combination. So that's why we're advancing that.

我還要強調的是，我們擁有大量與非小細胞肺癌患者群體相關的數據。這是 KEYNOTE-189。這是化療加骨療。您需要一種具有 KRAS 的強效化合物才能將其移至第一線。這就是我們正在嘗試玩的遊戲。所以很擁擠。但您要尋找的是一種具有巨大單一療法功效的強效化合物。但最重要的是，當你將它與例如 pembro 結合使用時，你可以保持劑量不變，保持不進行劑量調整的能力。這些數據讓我們感到興奮，因為我認為我們報告的 ORR 總體為 71%。這就是我們推進這項進程的原因。

The race for us is to get it in first line and then to think about other KRAS indications and IO-sensitive/insensitive and also other molecules that are coming through in the lung cancer space. And some of them are related to antibody drug conjugate. So we are very excited about our KRAS G12C program, 1084, which is moving to Phase III.

我們的競爭重點是將其作為第一線治療藥物，然後再考慮其他 KRAS 適應症和 IO 敏感/不敏感藥物，以及肺癌領域出現的其他分子。其中一些與抗體藥物偶聯物有關。因此，我們對即將進入第三階段的 KRAS G12C 專案 1084 感到非常興奮。

Our next question comes from Chris Shibutani with Goldman Sachs.

我們的下一個問題來自高盛的 Chris Shibutani。

Maybe focusing on the pipeline on areas that you do not highlight as often, specifically immunology. And then a lot of the discovery work that you talk about in CNS. With immunology with a TL1A, can you just help us understand where we are on the Crohn's study there and also the Pandion acquisition, like in just Phase II.

或許重點關注您不常強調的領域，特別是免疫學。然後您在 CNS 中談到了很多發現工作。透過 TL1A 的免疫學，您能否幫助我們了解克羅恩病研究以及 Pandion 收購的進展情況，例如僅處於第二階段。

And then CNS, you highlight how many folks you have doing discovery research. How do you feel about the distribution of your efforts in CNS there? So just 2 areas not highlighted in the press release, but I think are important to your overall portfolio.

然後是 CNS，您要強調有多少人正在進行發現研究。您對於自己在 CNS 的工作分配有何看法？因此，新聞稿中沒有強調這兩個領域，但我認為它們對您的整體投資組合很重要。

Thank you very much. So I'll first touch immunology and specifically in the TL1A space. So that TL1A, we think that it will be a highly effective -- the higher efficacy, and also not just in terms of efficacy, in terms of tolerability. That ulcerative colitis program Phase III has started already and is recruiting. We are hopeful that we will be announcing the opening of the Phase III and patients coming in for the Crohn's disease over the next few months. So we are very excited about moving TL1A eagerly and appropriately aggressively move it in Phase III to really sort of outline the really differentiated profile that we have seen for TL1A, and specifically, our compound.

非常感謝。因此我首先要談免疫學，特別是 TL1A 領域。因此，我們認為 TL1A 將是一種高度有效的藥物——具有更高的療效，並且不僅在療效方面，而且在耐受性方面。此潰瘍性結腸炎計畫第三階段已啟動並正在招募患者。我們希望在接下來的幾個月內宣布啟動第三階段研究並接收克羅恩病患者。因此，我們非常高興能夠熱切而適當地積極地推動 TL1A 進入第三階段，以真正勾勒出我們所看到的 TL1A 的真正差異化特徵，特別是我們的化合物。

I should also emphasize that we also are looking at TL1A not just within sort of inflammatory bowel disease, but we're also interested in other diseases. And one of the things that's really interesting about TL1A, it is blocking inflammation. But there is reasons to believe that it can have profound effects on fibrosis, and that's our interest in Crohn's disease.

我還要強調的是，我們不僅在發炎性腸道疾病中研究 TL1A，而且我們也對其他疾病感興趣。 TL1A 真正有趣的功能之一是它能夠阻斷發炎。但有理由相信它可以對纖維化產生深遠的影響，這就是我們對克隆氏症的興趣。

But there are other diseases, for example, in the lung where fibrosis is a really important component. And we will be interested to see those. We have other assets moving forward both from the Prometheus acquisition that is not the TL1A as well as other internal that are moving forward with alacrity.

但還有其他疾病，例如肺部疾病，其中纖維化是一個非常重要的組成部分。我們對此很感興趣。我們還有其他資產正在推進，既包括從 Prometheus 收購而來的資產（非 TL1A），也包括其他正在迅速推進的內部資產。

In relationship to neuroscience, we hope to be getting the readout with MK-8189. We have other programs that are moving and advancing. And we have made some commitments in the early discovery space in a BD standpoint to accelerate some of our works that have been made public.

就神經科學而言，我們希望能夠透過 MK-8189 獲得讀數。我們還有其他項目正在推動和發展。而我們從 BD 的角度在早期發現領域做出了一些承諾，以加速我們一些已經公開的作品的發布。

I think over the next 1 to 2 years, we'll see readouts Phase IIbs, Phase Is moving to Phase II. But I think at that point, we will be able to speak more fully. But I think the investment in neuroscience, I think, is critically important. From a health care unmet need, you have to list from an economic value to the health care system and population. Especially in the United States, neuro disease continues to be a really important place, and I would say neuro disease not just in terms of degenerative but -- not just classic neuro disease but in the psychiatry arena as well. And you've seen others advance business development in that space. We're interested in continuing in business development there, but also importantly, moving our own internal program, the lead program being MK-8189.

我認為在未來 1 到 2 年內，我們將看到 IIbs 階段的讀數，Is 階段正在轉向 II 階段。但我認為到那時我們就能更充分地交談了。但我認為對神經科學的投資至關重要。從醫療保健未滿足的需求來看，你必須列出醫療保健系統和人口的經濟價值。尤其是在美國，神經疾病仍然佔有非常重要的地位，我想說神經疾病不僅僅是退化性疾病，而且不僅僅是經典的神經疾病，還包括精神病學領域。而且您已經看到其他人在該領域推動業務發展。我們有興趣繼續在那裡開展業務，但同樣重要的是，推進我們自己的內部項目，主要項目是 MK-8189。

Our next question from Daina Graybosch.

下一個問題來自 Daina Graybosch。

I want to ask some on pneumococcal vaccine. You mentioned several times V116 is customized for adults 65 and older. In the ACIP meeting, they discussed a recommendation in adult 50 or older. And I wonder if you could comment on where you think that ACIP recommendation will end up for V116. And on V117, I wonder if you could talk about how the stack scene, which I believe is now in Phase I is customized for pediatric patients.

我想問一些關於肺炎鏈球菌疫苗的問題。您多次提到 V116 是針對 65 歲及以上的成年人量身定制的。在 ACIP 會議上，他們討論了針對 50 歲或以上成年人的建議。我想知道您是否可以評論一下您認為 ACIP 對 V116 的最終建議是什麼。在 V117 上，我想知道您是否可以談談堆疊場景是如何為兒科患者量身定制的，我認為現在處於第一階段。

Yes. Maybe I can start, Daina, and then Dean can add. Obviously, I would just start by saying we were very pleased with the overall tone and tenor of the discussion coming out of the ACIP meeting. And as you look at what we have with V116, we continue to believe -- if you look at the strength of the data behind that, and we've talked about -- Dean mentioned some of the clinical readouts that have come. But recall, we cover 83% of the serotypes-causing disease in adults. That's 30% higher than PCV20. So it's significant, and that was how it was specifically designed, targeting those serotypes which are most prevalent in adult disease.

是的。也許我可以開始，戴娜，然後迪恩可以補充。顯然，我首先要說的是，我們對 ACIP 會議討論的整體基調和基調非常滿意。當您查看 V116 的進展時，我們仍然相信 — — 如果您查看其背後的數據強度，並且我們已經討論過 — — Dean 提到了一些已經得出的臨床讀數。但請記住，我們涵蓋了 83% 的成人血清型致病疾病。這比PCV20高出30%。所以它很重要，這就是為什麼它被專門設計來針對成人疾病中最常見的血清型的原因。

As a result of that, we continue to believe the value proposition of V116 is very compelling. If you look at the cost effectiveness, it's going to be a very cost-effective vaccine. And as a result, I think that's why you started to see the ACIP ask questions about the 50 to 65 age cohort as well as the 65-plus.

因此，我們仍然相信 V116 的價值主張非常引人注目。如果從成本效益來看，這將是一種非常具有成本效益的疫苗。因此，我認為這就是為什麼你開始看到 ACIP 詢問有關 50 至 65 歲年齡組以及 65 歲以上年齡組的問題。

So I don't want to get ahead of the ACIP and their recommendation. But I would say our belief and conviction in the value of the data and the value this vaccine will bring for patients in the pneumococcal space is significant. And I would expect overall that we're going to see broad coverage coming out of the ACIP.

所以我不想超越 ACIP 和他們的建議。但我想說，我們對數據的價值以及這種疫苗將為肺炎球菌領域患者帶來的價值的信念和信心是巨大的。整體而言，我期望我們能夠看到 ACIP 得到廣泛的報告。

Yes. I would just add, again, we want to be respectful of ACIP and the FDA. But you did point out something that I think is something that clearly we took notice. When Rob talks about that 83% versus 50% and 30% more, and the specific question that you're asking about, 50 to 64, I would remind everyone that dropping that age for universal vaccination have been considered previously for other vaccines. And they could not come to a situation where they thought that it would be a good idea based on cost effectiveness and as such. And by increasing it from 50% to 83%, we believe that we changed the calculus, and that made why there is renewed interest in lowering that age based on the broader coverage given for V116.

是的。我還要補充一點，我們要尊重 ACIP 和 FDA。但您確實指出了一些我認為我們已清楚注意到的事情。當羅布談到 83% 與 50% 和多 30% 以及你所問的具體問題（50 至 64 歲）時，我想提醒大家，降低全民接種年齡此前也曾被考慮用於其他疫苗。他們無法認為從成本效益等方面來看這是一個好主意。透過將其從 50% 提高到 83%，我們相信我們改變了計算方法，這就是為什麼人們重新對降低該年齡產生了興趣，因為 V116 的覆蓋範圍更廣。

And I think there was a second question you had, Daina, about V117. I'll just maybe give a general answer, which is, obviously, if you look at the strategy of V116, it's the same strategy with V117: How do we develop an investigational PCV vaccine that is targeted specifically to those serotypes that cause disease in children, in peds, without hopefully causing untoward effects. And so it's a model that follows that. We've not given any details to the additional serotypes or our thinking. But just understand that if you look at the model of V116, V117 is the same thing in peds.

我覺得你還有第二個問題，戴娜，關於 V117。我可能只會給出一個一般性的答案，很明顯，如果你看看 V116 的策略，你會發現它與 V117 的策略相同：我們如何開發一種研究性的 PCV 疫苗，專門針對那些導致兒童、兒科疾病的血清型，並且希望不會引起不良影響。所以它是一個遵循這一點的模型。我們尚未透露其他血清型或我們想法的任何細節。但只要你看一下 V116 的模型，你就會明白，V117 在兒科中是同樣的東西。

Our next question comes from James Shin with Deutsche Bank.

下一個問題來自德意志銀行的 James Shin。

Firstly, I know Merck does not provide product-level guidance, but given WINREVAIR's importance and investor focus, can you provide any color on WINREVAIR contribution to guidance? And then second one is for Dean on REJOICE-Ovarian and I suppose precision oncology in general. But does the field know how much overlap there is between (inaudible) FRalpha? And then for patritumab, I know the data for HER3 shows high expression in advanced patients, but there's a lot of development in advanced space. So how does Merck envision patritumab to be positioned or sequenced?

首先，我知道默克不提供產品級指導，但考慮到 WINREVAIR 的重要性和投資者的關注度，您能否提供有關 WINREVAIR 對指導的貢獻的任何資訊？第二個是關於 REJOICE-Ovarian 的，我認為是關於精準腫瘤學的。但是該領域是否知道（聽不清楚）FRalpha 之間有多少重疊？然後對於 patritumab，我知道 HER3 的數據顯示在晚期患者中表達較高，但在晚期領域仍有很大的發展空間。那麼默克公司設想如何定位和排序 patritumab 呢？

Yes. Maybe, James, I'll start. And thank you for the question. The short answer is, unfortunately, we don't provide product-level guidance. So I don't think we want to get into trying to tell you what we see WINREVAIR as being a contributor in 2024.

是的。也許，詹姆斯，我先開始。感謝您的提問。簡短的回答是，不幸的是，我們不提供產品級指導。因此，我認為我們不想試圖告訴您我們認為 WINREVAIR 在 2024 年會做出什麼貢獻。

But with that said, I think it's important to make a few points just so you understand how we're seeing it. First of all, we're very excited to provide this novel treatment for patients with PAH. As you know, we think this will be a game changer in that space. We were well prepared for the launch. And I can tell you the launch, although very early, is going well so far. We've seen an increasing number of prescriptions being written. We've seen repeat prescriptions, and that's coming both from the COE space, from the Centers of Excellence, which is about 150 in the United States, as well as from non-COEs, which is a good development.

但話雖如此，我認為有必要闡明幾點，以便您了解我們是如何看待這個問題的。首先，我們非常高興為 PAH 患者提供這種新型治療方法。如你所知，我們認為這將會改變該領域的遊戲規則。我們為此次發射做好了充分的準備。我可以告訴你們，雖然發表會還為時過早，但目前進展順利。我們看到開出的處方數量正在增加。我們看到了重複的處方，這些處方既來自 COE 領域，來自卓越中心（美國約有 150 個），也來自非 COE，這是一個很好的發展。

We've already begun making shipments to patients' homes. And hopefully, we'll have patients being dosed very soon, if not already.

我們已經開始將貨物運送到患者家中。希望我們能很快為患者提供藥物，即使現在還沒有。

And then I think the other thing I'd note is the prescribers as well as the locations are both from the Centers of Excellence and also non-COE. So that's something to note. And then finally, from a payer perspective, we're seeing good access. No real limits. In fact, we already have several payers who have established coverage policies. And I think as Caroline pointed out in the prepared comments, very consistent with the label and what we saw in STELLAR. But the fact that we've seen policies enacted giving coverage to patients already this quickly after launch, we see as a good sign.

然後我認為要注意的另一件事是，處方者和地點既來自卓越中心，也來自非卓越中心。這是值得注意的。最後，從付款人的角度來看，我們看到了良好的訪問。沒有真正的限制。事實上，我們已經有幾家付款人制定了承保政策。我認為，正如 Caroline 在準備好的評論中指出的那樣，這與標籤以及我們在 STELLAR 中看到的內容非常一致。但事實上，我們看到政策頒布後很快就為患者提供了保障，我們認為這是一個好兆頭。

It's obviously early. But everything so far looks quite good. So our confidence in a successful launch has not changed. We continue to see this consistent with our expectations. And as we move forward, we'll give you appropriate level of transparency. But I just want to give flavor, even though we can't give the specific guidance you were asking for.

顯然還早。但目前為止一切看起來都很好。因此，我們對成功發射的信心沒有改變。我們繼續認為這與我們的預期一致。隨著我們不斷前進，我們將為您提供適當程度的透明度。但我只是想提供一些風味，儘管我們無法提供您所要求的具體指導。

Dean, I'll let you take the second part of the question.

院長，我請你回答問題的第二部分。

Yes. So I'll just add a little bit in relationship to WINREVAIR. I think it's important to emphasize that the indication or the label that we have is a broad indication and is based on STELLAR. And there will be potential data flows that will continue to inform and strengthen the field. We have STELLAR and SOTERIA, which is open label. We have ZENITH, which is advanced, and that will look at mortality and morbidity; and HYPERION, which is in more -- earlier in the journey.

是的。因此我只想補充一些與 WINREVAIR 相關的內容。我認為需要強調的是，我們的指示或標籤是廣泛的指示，並且基於 STELLAR。並且會有潛在的數據流繼續為該領域提供資訊並加強該領域。我們有 STELLAR 和 SOTERIA，它們是開放標籤的。我們擁有先進的 ZENITH，可以研究死亡率和發病率；以及 HYPERION，它處於旅程的早期階段。

We have the European action that will happen in the second half of 2024. And I would just emphasize that this is something that health care professionals and self-administration is possible. And in relationship to that, there will be a demand for innovation, and we hope to provide that innovation as this becomes even more used in a self-administration standpoint.

我們的歐洲行動將於 2024 年下半年採取。與此相關，對創新的需求將會存在，我們希望隨著創新在自我管理的角度得到更廣泛的應用，能夠提供這種創新。

You asked a number of questions and many of the questions related, and some of it got blurred out, but some of it related to ovarian, but more broadly speaking, tissue targeting and ADCs. So I'll just give you an overview. When we look at the field, we look at cancers where there is IO and chemo and that combination. And where will we see that? We ask ourselves, can you combine an IO agent with a chemo agent? And we think about KEYTRUDA, but we also think about next-gen tissue targeting IO agents, such as the recent immune engagers that we have from Harpoon.

您問了許多問題，其中許多問題都相關，有些問題被模糊掉了，但有些問題與卵巢有關，但更廣泛地說，與組織靶向和 ADC 有關。我僅給你一個概述。當我們觀察這個領域時，我們關注的是存在IO和化療以及二者結合的癌症。我們將在哪裡看到它？我們問自己，你能將IO劑與化療劑結合嗎？我們考慮了 KEYTRUDA，但我們也在考慮下一代組織靶向 IO 藥物，例如我們最近從 Harpoon 獲得的免疫接合劑。

And then on the other hand, we think about chemo, we think of precision targeting like RAS, how can it combine? And we also think in terms of ADCs. And the specific case that you're talking about, you have HER3 patritumab. That's moving along in EGFR non-small cell lung cancer. In B7-H3, there's prominent data that's in small cell lung cancer, maybe in prostate. And for CDH6 itself, that ovarian data is quite interesting, and that's raludotatug.

另一方面，我們考慮化療，我們考慮像 RAS 這樣的精準靶向，它如何結合？我們也從 ADC 的角度來思考。您所談論的具體情況是，您有 HER3 patritumab。 EGFR 非小細胞肺癌正在經歷這項進展。在 B7-H3 中，有突出的數據表明它存在於小細胞肺癌中，也可能存在於前列腺癌中。對於 CDH6 本身來說，卵巢數據非常有趣，這就是 raludotatug。

At least for us, it's very interesting because the initial data with our partners in Daiichi Sankyo is striking to us. Because in that patient population, it looked like allcomers did extremely well and that in some situations, you think about a biomarker. But for the CDH6, the impact across sort of biomarker subsets was quite impressive. So I hope that gives you a general structure and we're happy to -- and thank you very much for that question.

至少對我們來說，這非常有趣，因為我們與第一三共的合作夥伴的初步數據令我們印象深刻。因為在該患者群體中，看起來所有患者都表現得非常好，在某些情況下，你會考慮生物標記。但對於 CDH6 來說，其對各種生物標記亞群的影響相當顯著。所以我希望這能給你一個整體結構，我們很高興——非常感謝你的提問。

Our next question comes from Umer Raffat with Evercore.

我們的下一個問題來自 Evercore 的 Umer Raffat。

I'm just trying to think through your next-gen HPV vaccine. And I guess, how should we think about potential penetration rates with a revaccination opportunity with the new broader-spectrum HPV, especially in patients who have already taken GARDASIL 9.

我只是想知道下一代 HPV 疫苗。我想，我們應該如何看待新出現的廣譜 HPV 疫苗的再接種機會的潛在滲透率，尤其是對於已經接種 GARDASIL 9 的患者。

Revaccination and relationship to HPV, is that what the question is?

重新接種疫苗與 HPV 的關係，這就是問題所在嗎？

The new (inaudible).

新的（聽不清楚）。

With the G9+. I'm struggling to answer your question because I first got to make a G9+ that works really, really well. And when I get that, that will be great because there are patient populations that I think would be extremely well served. But I would also emphasize that we've just talked about cancer. We talked about early-stage cancer. This is the time that you can really treat and potentially cure, but we're in the business of preventing cancers as well.

使用 G9+。我很難回答你的問題，因為我首先要製作一個運行得非常非常好的 G9+。當我得到它時，那將會很棒，因為我認為患者群體將得到極好的服務。但我還要強調的是，我們剛剛討論了癌症。我們討論了早期癌症。這是真正可以治療並可能治癒的時期，但我們也從事預防癌症的工作。

One of the questions that comes to us is that in certain patient populations, you want a vaccine that -- the data, for example, Scandinavia, it's 90-plus reduction -- 90% reduction in cancer incidents. And then the recent American Cancer Society. We are wondering whether if you make a G9+ vaccine, whether you can make the argument, if we're successful with the G9+ and what we hope to aspire for, whether you could fundamentally change how one recommends cancer screening for women in relationship to cervical cancer and also the reduction both in men and women of many other cancers outside of cervical cancer.

我們面臨的一個問題是，在某些患者群體中，你需要一種疫苗——例如，斯堪的納維亞半島的數據顯示，癌症發病率減少了 90% 以上——減少了 90%。接下來是最近的美國癌症協會。我們想知道，如果您開發 G9+ 疫苗，您是否可以提出論據，如果我們成功研發出 G9+，以及我們希望實現的目標，您是否可以從根本上改變人們建議女性進行子宮頸癌癌症篩檢的方式，以及降低男性和女性患子宮頸癌以外的許多其他癌症的幾率。

This is Caroline. I'll just add that as we sit here today, we all know there are many, many people around the world that have not received a vaccine to prevent them against, to help protect them from HPV-related cancers. With the possibility of improving upon G9 with a multivalent vaccine, we're hopeful that we can provide further protection, especially for different population groups. And we will price the vaccine appropriately based on the benefit that it will provide. So we're looking forward to continuing to see growth in GARDASIL and see how the science evolves with our clinical programs.

這是卡羅琳。我只想補充一點，今天我們坐在這裡，我們都知道世界上有許多人沒有接種疫苗來預防 HPV 相關癌症。由於有可能透過多價疫苗改進 G9，我們希望能夠提供進一步的保護，特別是針對不同族群。我們將根據疫苗帶來的益處對其進行合理定價。因此，我們期待繼續看到 GARDASIL 的成長，並看到科學如何隨著我們的臨床計畫而發展。

Our next question comes from Tim Anderson with Wolfe Research.

我們的下一個問題來自 Wolfe Research 的蒂姆·安德森。

I have a few questions on KEYTRUDA subcu. It may not be scientifically sexy, but of course, it could be quite commercially meaningful. So we'll see that data, I believe, later this year. Any risk whatsoever to that readout? Or can we consider it to be a slam dunk?

我對 KEYTRUDA subcu 有幾個問題。從科學角度來說，這也許並不吸引人，但當然，它具有相當的商業意義。所以我相信我們將在今年稍後看到這些數據。這個讀數有沒有什麼風險？或者我們可以認為這是一次灌籃嗎？

Second question is when the subcu launches in the U.S., presumably next year, will uptake be fast or slow or somewhere in between? And then eventually, how much can a subcu account for the franchise on a volume or a patient basis?

第二個問題是，當 subcu 在美國推出時（大概是明年），普及速度會很快、很慢還是介於兩者之間？那麼最終，從數量或病患數量來看，子專科醫院能為特許經營帶來多少利益呢？

So I'll take the first part of that. I remind myself, nothing is slam dunk once you place innovative drugs in patients. So I'll answer that question. But I think you highlighted really the pembro plus hyaluronidase that we're advancing. I would disagree a little bit. I do kind of think it's sexy in some ways. And that D77, we will be sharing that data by early 2025.

因此我將討論第一部分。我提醒自己，一旦將創新藥物投入患者體內，就沒有什麼是輕而易舉的。所以我來回答這個問題。但我認為您確實強調了我們正在推進的派姆單抗聯合透明質酸酶。我有點不同意。我確實認為它在某些方面很性感。我們將在 2025 年初之前共享 D77 數據。

The reason I think it's really an important innovation is to really increase the access. You've seen the number of early-stage cancer readout that are coming through with pembrolizumab and KEYTRUDA and especially in the earlier stages when we talk about KEYNOTE-671, when we talk about in renal cell carcinoma, where we have OS benefit. I think this is going to be really, really important for patients. It will also be important in patients for treatment, especially in those who have monotherapy and those especially combos with oral agents because it just makes it so much more accessible. So we think this is an important program and that it could have substantial impact on patients and their access to PD-1, where we know the foundational elements of PD-1. And in terms of financial...

我認為這是真正一項重要創新的原因在於它確實增加了訪問量。您已經看到了使用 pembrolizumab 和 KEYTRUDA 治療的早期癌症病例的數量，特別是在早期階段，當我們談論 KEYNOTE-671 時，當我們談論腎細胞癌時，我們具有 OS 益處。我認為這對患者來說非常非常重要。它對於患者的治療也很重要，特別是對於單一療法和口服藥物聯合治療的患者，因為它使治療更容易獲得。因此，我們認為這是一個重要的項目，它可能會對患者及其獲得 PD-1 的機會產生重大影響，我們了解 PD-1 的基礎元素。從財務方面來說…

Yes. Maybe, Tim, I'll just provide some commentary on your questions on uptake and how much of the patient population this can account for. As we think about uptake of this opportunity, I would first point out that we see really -- it starts with the strength of the clinical data underlying the IO agent itself. So it's more about the confidence they have in KEYTRUDA. And then secondarily, it's about the delivery mechanism, which is important as we think about obviously leveraging the data we have and just the breadth of what KEYTRUDA is.

是的。也許，提姆，我只是想對你關於吸收率的問題以及這能佔到多少患者群體的問題提供一些評論。當我們考慮利用這個機會時，我首先要指出的是，我們真正看到的是──它始於IO藥物本身的臨床數據的強度。所以這更多的是他們對 KEYTRUDA 的信心。其次，是關於交付機制，這很重要，因為我們考慮利用我們擁有的數據和 KEYTRUDA 的廣度。

But I will tell you that as we think about bringing this forward when we do launch, our goal will be the price appropriately with the goal of driving quick adoption. So we do want to see adoption happen, and we do think you will see it. Obviously, if you look at then the size of the patient population where it could be, just to give you a sense, by 2028, if we look at the patients who are on monotherapy with KEYTRUDA who are using combinations with orals and those who are moving into earlier stages of disease through some of our adjuvant and neoadjuvant areas with KEYTRUDA, that represents about 50% of the patient population at that time. So that is really the addressable market for what we see the subcu offering to be.

但我要告訴你，當我們考慮在推出產品時提前推出它時，我們的目標是適當定價，以便推動快速採用。因此，我們確實希望看到採用的發生，並且我們確實認為您會看到它。顯然，如果您看一下患者群體的規模，到 2028 年，如果我們看看使用 KEYTRUDA 單一療法的患者，使用口服藥物聯合治療的患者，以及透過我們的一些 KEYTRUDA 輔助和新輔助治療領域進入疾病早期階段的患者，這將佔當時患者群體的約 50%。所以，這確實是我們所看到的 subcu 產品的潛在市場。

And potentially, we're not foreclosing the opportunity to also look into the metastatic setting and people being given care in institutions as well as those moving outside of the institutions. But obviously, the value to the patient is ease of use, ability to use it outside of the hospital setting. The time in chair is obviously less if you're getting a subcu versus an IV. And then from a cost to the health care system, the ability to not have a patient sitting in the chair for as long allowing for more patients to move through, we think, actually drives access and improves the providing of care as well. So we see it both beneficial from a patient perspective and from the provider perspective, and that's why we do think you'll see uptake of this important medicine when we bring it forward.

而且，我們可能不會放棄研究轉移性環境和在機構內接受護理的患者以及在機構外接受護理的患者的機會。但顯然，對病人來說，價值在於易用性，以及在醫院外使用的能力。如果您接受皮下注射而不是靜脈注射，那麼在椅子上的時間顯然會更短。然後從醫療保健系統的成本來看，讓患者不必長時間坐在椅子上，從而讓更多的患者能夠就診，我們認為這實際上推動了就診機會並改善了醫療服務。因此，我們認為它從患者和提供者的角度來看都是有益的，這就是為什麼我們確實認為，當我們推出這種重要藥物時，您會看到它被接受。

Our next question comes from Louise Chen with Cantor.

下一個問題來自 Cantor 的 Louise Chen。

I just wanted to ask you for ASCO on June 3. Are there any specific readouts updates that you're very excited about presenting?

我只是想問您關於 6 月 3 日的 ASCO 的問題。

I think there's just going to be a stream of data. There's going to be follow-ups and a series of KEYNOTE, whether it be gastric, hepatocellular, biliary, bladder, non-small cell lung cancer. There will be discussions of many of the programs that I think you're beginning to see coming up in the clinical trial website in relationship to a whole series of Phase III related to molecules that you're familiar with, but also molecules that are sort of earlier in our Phase III development, ranging from bomedemstat to the KRAS program, to many of the ADCs and the updates that we've shown in relationship to not just the Daiichi Sankyo ADCs, but the other ADCs, whether it be TROP2 Claudin or (inaudible). So you'll have a whole full array of discussions of those compounds, some at the ASCO, but some at the ASCO investor event.

我認為這只是一串資料流。將會有後續報導和一系列主題演講，無論是胃癌、肝細胞癌、膽癌、膀胱癌或非小細胞肺癌。我們將討論許多項目，我認為您會在臨床試驗網站上開始看到這些項目，這些項目與一系列與您熟悉的分子相關的 III 期研究有關，但也包括我們 III 期開發中較早的分子，從 bomedemstat 到 KRAS 項目，再到許多 ADC 和我們展示的與第一三共 ADC 相關的更新，以及其他 ADC，無論是 TR2 Claudin OP2（C3）。因此，您將對這些化合物進行全面的討論，有些在 ASCO 上，有些在 ASCO 投資者活動上。

Great. Thanks, Louise. I know we have several more people in the queue. We're going to go an extra 5 or 10 minutes to try to get to as many questions as possible.

偉大的。謝謝，路易絲。我知道排隊的人還多著。我們將額外花 5 到 10 分鐘來解答盡可能多的問題。

Our next question comes from Trung Huynh with UBS.

我們的下一個問題來自瑞銀的 Trung Huynh。

Trung Huynh from UBS. On the WINREVAIR launch, thanks for the comments today on access and coverage. On approval, you noted that 2/3 of your PAH patients would likely Part D and third commercial. Perhaps can you expand on the free assistance program that you're hoping to initiate? And what proportion of those Part D patients do you think could be receiving free product this year?

瑞銀的 Trung Huynh。關於 WINREVAIR 發布會，感謝您今天對訪問和報導的評論。在批准時，您指出 2/3 的 PAH 患者可能需要 D 部分和第三個商業產品。也許您可以詳細說明一下您希望啟動的免費援助計劃？您認為今年有多少比例的 D 部分患者可以獲得免費產品？

Yes. I appreciate the question. So as you point out, we are very focused on ensuring that patients get access to the medicine. We're very much committed to it. And that's why we do have -- in addition to our normal programs we would run, we do have the access program we run. That program is actually independent of our commercial operations. We don't really report data coming out of that because it's run through a separate foundation and with the goal, frankly, of making sure that patients get medicines there. So that is available. It can be accessed on our website, and we're committed to making sure patients get the medicine. But specifics on that, we're not going to go into.

是的。我很感謝你提出這個問題。正如您所指出的，我們非常注重確保患者能夠獲得藥物。我們對此非常致力於。這就是為什麼我們除了運行正常程序之外，還運行訪問程序。該計劃實際上與我們的商業運營無關。我們實際上並沒有報告由此產生的數據，因為它是由一個單獨的基金會運行的，坦率地說，其目標是確保患者能夠在那裡獲得藥物。因此這是可行的。它可以在我們的網站上查閱，我們致力於確保患者獲得藥物。但我們不會深入討論這個具體細節。

Our next question comes from Carter Gould with Barclays.

我們的下一個問題來自巴克萊銀行的卡特·古爾德。

Maybe on your personalized cancer vaccine with Moderna, as the Phase III sort of nears completion of enrollment, it of course begs the question around the potential to sort of file based on the existing data you have. Can you maybe just update us on your thoughts there and whether you think you still need Phase III data or manufacturing would preclude an early filing? Any help there would be appreciated.

或許在您與 Moderna 合作研發的個人化癌症疫苗上，隨著第三階段的招募工作即將完成，這當然會引出一個問題，即您是否可以根據現有數據進行歸檔。您能否向我們介紹一下您的想法，以及您是否認為仍需要第三階段資料或製造是否會妨礙提前提交申請？任何幫助都將不勝感激。

Yes, I'll take that. I mean I don't want to speak about whether the FDA will take what action or not. But I'll just reemphasize to everyone what is exciting about our INT program and our excitement working with Moderna. So here, we're inducing and coaxing sort of immunity. And we're mixing it with a drug that's well known that unleashes pre-existing immunity, which is KEYTRUDA.

是的，我接受。我的意思是我不想談論 FDA 是否會採取什麼行動。但我只想向大家再次強調我們的 INT 計劃令人興奮的地方以及我們與 Moderna 合作的興奮之情。所以在這裡，我們正在誘導和誘導某種免疫力。我們將它與一種眾所周知的可以釋放預先存在的免疫力的藥物混合，這種藥物就是 KEYTRUDA。

What we have in our hands is a randomized, early-stage IO sensitive trial, where it is very clear of the contribution of components of the INT, not in immunogenicity, but in clinical benefit. So I just want to highlight that about our data as one looks at the data of others.

我們正在進行一項隨機、早期 IO 敏感性試驗，其中 INT 各成分的貢獻非常明確，不是在免疫原性方面，而是在臨床益處方面。因此，我只想強調一下我們的數據與其他人的數據的差異。

We also have begun to show that we are moving it in Phase III in adjuvant melanoma and adjuvant non-small cell lung cancer and our ability to move that with speed and rigor but get patients recruited, which is going well, I think will be very important because you're going to need a Phase III regardless of what the FDA decides on an accelerated approval or not. And so that's what we're focused on.

我們也開始表明，我們正在將其推進至輔助黑色素瘤和輔助非小細胞肺癌的第三階段，我們有能力快速、嚴格地推進這一進程，但要招募患者，這項工作進展順利，我認為這將非常重要，因為無論 FDA 決定是否加速批准，您都需要進行第三階段研究。這就是我們所關注的重點。

We're also focused on looking at other IO-sensitive tumors such as renal cell carcinoma. And I would just emphasize the strength of the data in relationship to durability is being answered. The ability for us to open these trials and successfully advance it is being answered. And we clearly have work to do with our colleagues who we respect deeply for what they've done in relationship to manufacturing.

我們也專注於研究其他IO敏感性腫瘤，例如腎細胞癌。我只想強調與耐用性相關的數據的強度正在得到解答。我們能否開啟這些試驗並成功推進，正在得到解答。顯然，我們需要與我們的同事一起努力，我們非常尊重他們在製造業方面所做的貢獻。

Any -- all mRNA vaccine, I mean, they've really pushed the envelope here. Our ability to do that will be important to make this an important treatment. As far as the FDA's decision, the FDA will need to make their decision as to how they consider the opportunity.

任何——所有 mRNA 疫苗，我的意思是，他們都已經真正突破了極限。我們做到這一點的能力對於使其成為重要的治療方法至關重要。就 FDA 的決定而言，FDA 將需要就如何考慮這個機會做出決定。

Our next question comes from Chris Schott with JPMorgan.

下一個問題來自摩根大通的 Chris Schott。

Just a couple of GARDASIL questions. You're pointing to a more evenly distributed China sales this year, and it seems like a tougher 2Q comp. But can you just directionally talk about growth for GARDASIL more broadly for the year? I guess the heart of it is still a healthy growth asset for you this year. And the second one on GARDASIL is if we were to move to a single dose of GARDASIL-9, what does that mean commercially and from a sales perspective for the franchise?

我只想問幾個有關 GARDASIL 的問題。您指出，今年中國市場的銷售分佈更加均勻，但第二季的銷售情況似乎更為艱難。但是您能否更廣泛地談談今年 GARDASIL 的成長方向？我想它的核心對你今年來說仍然是健康的成長資產。關於 GARDASIL 的第二個問題是，如果我們改用單劑量 GARDASIL-9，從商業和銷售角度來看，這對特許經營意味著什麼？

Chris, it's Caroline. So in terms of the phasing of GARDASIL, as you pointed out, during 2023, we saw in China an acceleration of the shipment from the second half of the year to the first half of the year, specifically to the second quarter. What that's done is it's provided an actual tailwind to revenue growth in the first quarter for China, but it will provide a headwind more significant in the second quarter. And that's what we've called out.

克里斯，我是卡洛琳。因此，就 GARDASIL 的分階段實施而言，正如您所指出的，在 2023 年，我們看到中國從下半年到上半年，特別是第二季的出貨量加速成長。此舉確實為中國第一季的營收成長提供了順風，但將在第二季帶來更顯著的阻力。這就是我們所呼籲的。

As we look at overall growth for GARDASIL, given where we are with the level of vaccinations across the world, given the manufacturing that we have been scaling up, we're confident in our ability to continue to drive growth during 2024. And in 2025, we will see our manufacturing capacity unconstrained so enabling us to further supply and support the market.

當我們審視 GARDASIL 的整體成長時，考慮到我們目前在全球的疫苗接種水平，考慮到我們一直在擴大的生產規模，我們有信心在 2024 年繼續推動成長。

As we've talked in the past, our opportunities for growth are significant as we look to continue to improve on adolescent vaccination rates, as we look to improve upon gender-neutral vaccinations, as we look to really activate the mid-adult segment, but increasingly get to the lower-income and middle-income markets, which will come at a different price point.

正如我們過去所說的，我們的成長機會很大，因為我們希望繼續提高青少年疫苗接種率，我們希望改善性別中立疫苗接種率，我們希望真正激活中成年人群體，但越來越多地進入低收入和中等收入市場，這將以不同的價格點出現。

As we sit here today, continue to be confident in the outlook for GARDASIL over both the near and the long term. As we look at the possibility of a single dose of GARDASIL, the study that we are conducting will be a comprehensive study and will take some time to unfold. What we're seeing in the marketplace currently is where certain low-income markets are implementing a single-dose regimen, they are also increasing the numbers of people they are vaccinating by broadening the age cohort or also opting to vaccinate males at this stage. We'll have to see long term how the data plays out with regards to a single dose to ensure that we will price our vaccine based on the benefit that we're bringing and we vaccinate as many people in the world that we can.

今天我們坐在這裡，對 GARDASIL 的近期和長期前景繼續充滿信心。當我們考慮單劑量 GARDASIL 的可能性時，我們正在進行的研究將是一項綜合性研究，並且需要一些時間才能展開。我們目前在市場上看到的情況是，某些低收入市場正在實施單劑量接種方案，他們還透過擴大年齡層或選擇在此階段為男性接種疫苗來增加接種疫苗的人數。我們必須長期觀察單劑量數據如何發揮作用，以確保我們的疫苗定價是基於我們帶來的好處，並為世界上盡可能多的人接種疫苗。

Your next question comes from Luisa Hector with Berenberg.

您的下一個問題來自 Berenberg 的 Luisa Hector。

I also have questions on the WINREVAIR launch. I just wanted to check how straightforward the subcutaneous administration is and when you might expect to launch an auto-injector. Also, should we actually expect the Part D access to come online at a similar pace as commercial? I'm just not sure whether that's something that's maybe sitting more into next year.

我對 WINREVAIR 的發布也有一些疑問。我只是想檢查皮下注射是否簡單，以及何時可能需要啟動自動注射器。此外，我們是否真的應該期望 D 部分接入能夠以與商業接入類似的速度上線？我只是不確定這是否是明年才會發生的事情。

And if I can, just another question on that with Part D is that you price for the Part D restructure next year. How do you expect payers to behave when this happens. I can see that the payer will take on a greater burden for higher-priced oral therapies. Do you expect some pushback within the actual drug that you would have higher rebates at that point? Or do you think that incremental burden for the payers might be spread more broadly across all products? It's a kind of bigger-picture question that WINREVAIR brings it into focus.

如果可以的話，關於 D 部分的另一個問題是，您是否為明年的 D 部分重組定價。當這種情況發生時，您希望付款人如何表現。我可以看到，對於價格較高的口服療法，付款人將承擔更大的負擔。您是否預期實際藥品價格會遭遇一些阻力，導致您獲得更高的回饋？或者您認為付款人的增量負擔可能會更廣泛地分攤到所有產品上？這是一個更大的問題，WINREVAIR 將這個問題聚焦到焦點。

So this is Dean. I'll answer your questions in terms of delivery of WINREVAIR. We have it in a vial, and we have it in a situation where both a health care provider or self-administration is both feasible, possible and will be used. We believe that the vast majority with time that people will use it as self-administration. This is a patient population that's quite used to doing injection. So we think that, that will be able to navigate and that the patients will get access.

這就是 Dean。我將回答您有關 WINREVAIR 交付的問題。我們將其裝在小瓶中，並且我們將其放置在醫療保健提供者或自我管理都是可行、可能並且將被使用的情況下。我們相信隨著時間的推移絕大多數人會將其用作自我管理。這是一個相當習慣注射的患者群。所以我們認為，這將能夠導航並且患者將能夠訪問。

But as you point out, further innovation will be demanded for, and an auto-injector will be critically important. We are doing the studies right now to evaluate how do we provide such an option, and we hope to have those options and those plans more public in the near future. But we agree with you totally in the fact that a future auto-injector will be important.

但正如您所指出的，還需要進一步的創新，而自動注射器至關重要。我們現在正在進行研究，以評估如何提供這樣的選擇，我們希望在不久的將來讓這些選擇和計劃更加公開。但我們完全同意您的觀點，未來的自動注射器將會非常重要。

And Luisa, this is Caroline. At this stage, we are seeing a real acceptance of the value proposition of WINREVAIR in the United States. We're seeing policy for coverage equally across both the Medicare and Medicaid patient population as well as the commercial segment. So as we move forward, we'll look forward to just helping as many patients as we can across all of those segments, irrelevant of their coverage.

路易莎，這是卡洛琳。現階段，我們看到 WINREVAIR 的價值主張在美國得到了真正的接受。我們看到，醫療保險和醫療補助患者群體以及商業領域的覆蓋政策都是平等的。因此，隨著我們不斷前進，我們將期待盡力幫助各個領域盡可能多的患者，無論他們是否受到覆蓋。

Our next question comes from Seamus Fernandez with Guggenheim.

我們的下一個問題來自古根漢的 Seamus Fernandez。

Wanted to ask actually about your RSV-targeted antibody, how you're thinking about that, the optionality for it and the market size and Merck's potential participation in this market as it relates to the competitors' global supply constraints at this point in time. It seems like coming to market more aggressively or as aggressively as possible could actually make for a meaningful market opportunity for Merck.

想問你們針對 RSV 的抗體，你是如何看待它的，它的可選性和市場規模，以及默克在這個市場的潛在參與，因為它與競爭對手目前的全球供應限制有關。看來，更積極或盡可能積極地進入市場實際上可以為默克創造有意義的市場機會。

And then just a follow-up. Rob, I wanted to just get your sort of qualitative view 3 years, 4 years in thinking about the evolution of the business. 2028-2029 still represents a meaningful challenge with KEYTRUDA. But as you look forward to the rest of this year and heading into 2025, how important is business development to Merck from here in terms of the size and type of acquisitions I think investors have certainly applauded what Merck has executed on in the last year for sort of mid- to later-stage assets.

然後只是後續行動。羅布，我只是想了解你對過去 3 年、4 年業務發展的定性看法。 2028-2029 年對 KEYTRUDA 來說仍然是一個重大挑戰。但是，當你展望今年剩餘時間和進入 2025 年時，就收購的規模和類型而言，業務發展對默克來說有多重要？

Yes. So I'll take the RSV question. So clesrovimab, we're excited about it. As many of the people know, it's a monoclonal antibody and it's a way to get passive immunity to infants. We think it's really important as we have seen recently. And ours is a single fixed dose and has the durability in terms of covering a whole RSV season, I think, is critically important. And the ability to give this to an infant any time and -- versus, for example, alternative strategies, which is maternal vaccination.

是的。因此我將回答 RSV 問題。因此，我們對 clesrovimab 感到非常興奮。許多人都知道，它是一種單株抗體，是讓嬰兒獲得被動免疫的一種方法。正如我們最近看到的那樣，我們認為這確實非常重要。我們的藥物是單劑量固定劑量，能夠持久覆蓋整個呼吸道合胞病毒季節，我認為這一點至關重要。並且可以隨時為嬰兒接種疫苗——而不是其他替代策略，例如母體接種疫苗。

And then also, we believe that this will be a distinguished monoclonal antibody and it's high barrier to resistance. So we're excited about moving and -- seeing that data and moving with both speed and rigor to get this to the market because we think it will be an important contributor, especially given what we've seen in the RSV season just this past season.

而且我們也相信這將是一種傑出的單株抗體，並且具有很強的抗藥性。因此，我們很高興看到這些數據，並迅速而嚴格地將其推向市場，因為我們認為它將是一個重要的貢獻者，特別是考慮到我們在上個賽季的 RSV 賽季所看到的情況。

I do want to just take this one moment to just say it's not just the RSV vaccine that we're very excited. We're also very excited because it's very much in the lay press in our dengue V181, which is a live attenuated tetravalent vaccine. And we're moving with equal eagerness to move that forward into Phase III, as we've already seen data from our colleagues in Institute Butantan about the effectiveness and efficacy of this vaccine.

我確實想花一點時間來說明一下，讓我們感到非常興奮的不僅僅是 RSV 疫苗。我們也非常興奮，因為我們的登革熱 V181 疫苗廣受媒體關注，它是一種減毒活四價疫苗。我們同樣熱切地希望將其推進到第三階段，因為我們已經從布坦坦研究所的同事那裡看到了有關該疫苗的有效性和功效的數據。

But I'll turn it back to Rob.

但我會把它交還給 Rob。

Yes. No. Thanks for the question. And so if I would just kind of, I guess, think a little bit about where we've been in over the last 3 years, a few points I would want to raise. One, I think we've made tremendous progress in a relatively short period of time, and I give all credit to Dean, to our R&D colleagues for what they've been able to do, how they have been able to really move just flawlessly products through our pipeline. It's amazing you think of it now 3 years in, we haven't had really any major failures. The one maybe hiccup with islatravir, but that's coming back. And so I feel very proud of what our colleagues in R&D have been able to do.

是的。不，謝謝你的提問。因此，如果我能稍微思考過去 3 年我們的情況，我想提出幾點。首先，我認為我們在相對較短的時間內取得了巨大的進步，我把所有的功勞都歸功於 Dean，歸功於我們的研發同事，感謝他們所做的一切，感謝他們如何能夠完美地將產品通過我們的管道。想想看，令人驚訝的是，三年過去了，我們並沒有遭遇任何重大失敗。伊拉曲韋 (islatravir) 可能會引起一些問題，但很快就會好起來。因此，我對我們的研發同事所取得的成就感到非常自豪。

And then I think about from a commercial perspective, from a manufacturing perspective, we're pulling the products through, we're showing value. The fact that we're ready for the launch with WINREVAIR shows how we can build capability very quickly. We did it in KEYTRUDA, we did it in JANUVIA and now we're doing it in WINREVAIR, and we'll do it in new spaces coming forward. So we feel very good about that. So across all elements, R&D, commercial, manufacturing, the business is delivering.

然後我從商業角度、從製造角度思考，我們正在推動產品的發展，展現價值。事實上，我們已經準備好透過 WINREVAIR 進行發布，這表明我們能夠非常快速地建立能力。我們在 KEYTRUDA 中做到了這一點，在 JANUVIA 中做到了這一點，現在我們在 WINREVAIR 中也做到了這一點，而且我們將在未來的新領域中也做到這一點。因此我們對此感到非常高興。因此，從研發、商業到製造等所有要素來看，業務都在順利進行中。

And so as we sit here today, if our clinical success continues, I think you're going to see us with a more diversified set of growth drivers over time than, frankly, we've had in many years, if ever. And that's very important. And it all is really what leads to the confidence you've heard me express in other settings, that I'm increasingly less focused on 2028. And I would remind you, by the way, it's a staggered LOE. So it's 2028 in the U.S.; in China, it's 2031; in Europe, in 2032 and in Japan. So it's not a one-moment event. It actually happens over time.

所以，今天我們坐在這裡，如果我們的臨床成功持續下去，我想你會看到我們隨著時間的推移擁有比過去許多年甚至任何時候都更加多樣化的成長動力。這非常重要。而這一切其實就是讓我在其他場合表達信心的原因，我越來越不關注 2028 年。所以在美國是 2028 年；中國是2031年；在歐洲，2032 年和日本。所以這不是一個瞬間發生的事件。事實上，隨著時間的推移，它就會發生。

But that being said, as you've heard me say, I see it is more of a hill than a cliff. And my confidence that we're going to come back with fast growth after that is very high. And we're very focused on the sustainable engine from 2030 to 2040 at this point. So I feel good about where we are, but I just want to reinforce it's a team effort, and I've been blessed with a great team.

但話雖如此，正如你聽到我說的，我認為它更像是一座小山，而不是一座懸崖。我非常有信心，我們將會在此之後恢復快速成長。目前，我們非常關注 2030 年至 2040 年的永續引擎。所以我對我們的現狀感到很滿意，但我只想強調這是團隊努力的結果，我很幸運能擁有一支偉大的團隊。

Great. Thank you, Seamus, and thank you all for your time and your interest today. I'm hoping to see many of you at our ASCO event on June 3 or at a few of the conferences that we'll be attending this quarter. So thank you all very much.

偉大的。謝謝你，西莫斯，也謝謝你們今天的時間和關注。我希望能在 6 月 3 日的 ASCO 活動或我們本季將參加的幾個會議上見到你們。非常感謝大家。

Thank you. And that does conclude today's conference. We thank you for your participation. At this time, you may disconnect your lines.

謝謝。今天的會議到此結束。我們感謝您的參與。這時，你可以斷開你的線路。