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.

謝謝你的支持。歡迎參加默克公司第一季銷售和收益電話會議。 （操作員說明）此通話正在錄音。如果您有任何異議，您可以此時斷開連接。

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

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

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。董事長兼執行長 Rob Davis 將在今天的電話會議上發表演說；卡洛琳‧利奇菲爾德，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.

在開始之前，我想指出一些事項。您會看到我們的 GAAP 結果中有一些項目，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，我們已將這些數據排除在我們的非公認會計準則績效之外，並在我們的新聞稿中提供了調節表。

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陳述可能被視為 1995 年美國私人證券訴訟改革法案安全港條款含義內的前瞻性陳述。層的責任，並面臨重大風險和不確定性。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提出的結果有重大差異。

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.

我們向SEC 提交的文件（包括第1A 項和2023 年10-K）確定了某些風險因素和警告性聲明，這些因素和警告性聲明可能導致公司的實際結果與我們今天早上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，我們的演講者準備好的演講將附有幻燈片演示。這些投影片以及我們的收益發布、今天準備的評論和我們向 SEC 提交的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.

有了這個，我想把電話轉給羅布。

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。 2024 年伊始，我們的業務持續保持強勁勢頭。我們正在利用創新的力量來推進我們的深層管道，並最大限度地發揮我們廣泛的商業產品組合的影響，以造福患者。我們推動了關鍵治療領域的強勁成長，執行了策略性業務發展，目前正在心臟代謝領域推出一款重要的新產品，同時也為腫瘤疫苗領域另外兩種重要候選藥物的潛在批准和上市做準備。我們業務的各個領域都面臨重大機遇，我們高度重視實現這些機會。

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，他們正在不懈努力，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，我們的 WINREVAIR 獲得 FDA 批准，這是一種治療成人肺動脈高壓的一流療法，肺動脈高壓是一種罕見的進行性且最終危及生命的疾病。這標誌著我們公司實現了一個重要的里程碑。它體現了我們策略重點的價值，並展示了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.

自從將 WINREVAIR 添加到我們的產品線以來僅兩年多，我們現在的注意力轉向了強大的商業發布的執行，我們已經看到了處方。我們看到了積極影響多環芳烴患者生活的巨大機會。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優先事項。我們已經證明，我們可以利用我們深厚的發現能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來增加顯著的價值，這些共同可以加速開發並實現廣泛的全球訪問為有需要的患者提供重要的醫學發現。

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.

轉向我們第一季的業績。我們實現了強勁成長，反映出對我們創新產品組合的強勁需求。我們很高興在更新後的全年指引中反映這一勢頭，卡羅琳稍後將談到這一點。轉向我們更廣泛的研究工作。我們致力於推動我們廣泛且多樣化的前沿項目管道，以造福患者。在疫苗方面，我們持續開拓新方法來優化疾病預防。在 HPV 方面，我們正在 GARDASIL 奠定的基礎上進一步減輕某些 HPV 相關癌症和疾病的全球負擔，方法是透過一種新的多價 HPV 疫苗提供更廣泛的保護，並產生數據來清楚地證明單一GARDASIL -9 劑量為16 至26 歲的男性和女性提供了與批准的3 劑量方案相當的長期保護。

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，我們提供了有關V116 的更多令人信服的數據，這是一種專門設計用於幫助65 歲及以上成年人預防大多數侵襲性肺炎球菌疾病的疫苗，並期待其在6月份獲得批准。這些計劃中的每一個都是我們可以為全球範圍內的廣大人群提供有意義的保護的平台。在愛滋病毒方面，我們與吉利德合作，分享了我們在治療環境中每週一次聯合使用伊拉曲韋和來那卡韋的振興計劃的有希望的數據。我們正在積極推進我們的綜合臨床計劃，該計劃的重點是治療和預防策略，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，我們從不同的產品線啟動了多個新候選藥物的後期項目，努力擴大我們對患者的影響並鞏固我們的長期領導地位。最後，在我們的深層管道中，我們在一系列治療領域擁有顯著的臨床動力。尖端科學是我們的核心，我相信默克有能力為病患、股東和所有利害關係人提供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，隨著持續的臨床成功，該引擎將在未來十年及以後帶來更加多元化的成長動力組合。我想再次認可我們全球組織所做的巨大努力。我的信心非常強大，而且不斷增強，我們有能力在這勢頭的基礎上再接再厲，在今年和未來推動患者影響力和價值創造。這樣，我就把電話轉給卡洛琳。

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.正如羅布所指出的那樣，我們今年開局良好，業務強勁增長，這增強了我們對前景的信心。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活，使我們能夠繼續為患者、客戶和股東提供長期價值。現在轉向我們第一季的業績。公司總營收為 158 億美元，成長 9%，排除外匯影響則成長 12%。匯率的影響主要是由阿根廷比索貶值推動的，而阿根廷比索貶值在很大程度上被與市場慣例一致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.

以下收入評論將以換算為基礎。在腫瘤學和疫苗的推動下，我們的人類健康業務繼續保持成長勢頭，實現 13% 的兩位數成長。我們的動物保健業務中伴侶動物和牲畜產品的銷售額均成長了 4%。轉向我們主要品牌的表現。在腫瘤學領域，由於早期癌症的使用量增加以及轉移適應症的持續強勁需求，KEYTRUDA 的銷售額增長了 24%，達到 69 億美元。在美國，KEYTRUDA 在多種腫瘤中生長。在早期癌症中，這一增長主要歸因於 KEYNOTE-671 和 KEYNOTE-091 上市後的非小細胞肺癌。

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.

在轉移性治療中，我們看到最近推出的 KEYNOTE A39 在第一線晚期尿路上皮癌的應用強勁。在美國以外，KEYTRUDA 的成長是由早期癌症（包括高風險早期三陰性乳癌和腎細胞癌）的持續吸收以及轉移性疾病患者的持續強勁需求推動的。符合阿根廷市場慣例的與通貨膨脹相關的價格上漲也促進了成長。 Lynparza 和 Lenvima 的聯盟收入分別成長了 7% 和 10%。由於 FDA 批准 LITESPARK-005 用於某些先前接受過治療的晚期腎細胞癌患者的額外適應症以及某些 VHL 疾病相關腫瘤的吸收增加，WELIREG 的銷售額增長了一倍多，達到 8500 萬美元。

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.

在全球需求的推動下，我們的疫苗產品組合在 GARDASIL 的帶動下實現了強勁增長，增長了 17%，達到 22 億美元。銷售額也受益於中國的出貨時間和美國 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%。牲畜銷售成長是由價格走勢以及對生豬和家禽產品的需求所推動的。伴侶動物的成長反映了價格走勢。

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其餘部分，我的評論將基於非公認會計原則。毛利率為 81.2%，成長 4.3 個百分點，原因是今年年初生效的 KEYTRUDA 和 GARDASIL 專利費率降低以及有利的產品組合。營運費用下降 4%，至 64 億美元，本季與收購 Harpoon Therapeutics 相關的 6.56 億美元費用低於一年前某些業務開發交易的 14 億美元費用。扣除這些費用，營運費用增加了 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.

我們仍然致力於適當投資，以實現我們昂貴的早期和後期管道的承諾，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%，其中包括未記錄任何稅收優惠的 Harpoon 交易的影響。總計每股收益為 2.07 美元，其中包括 Harpoon 相關指控的 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%.

現在轉向我們的 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指引。我們目前預計營收將在 6,310 萬美元至 643 億美元之間，反映出營收年增 5% 至 7%，其中包括外匯的負面影響。在此範圍的中點，我們業務的營運實力約為6 億美元，但以4 月中旬匯率計算，外匯帶來的約4 億美元的增量逆風部分抵消了這一增量，導致全年外匯帶來的負面影響約為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.

我們目前的毛利率假設預計約為 81%。我們估計的營運費用範圍在 2,520 萬美元至 261 億美元之間，其中不考慮額外的重大潛在業務開發交易。其他費用預計約 2.5 億美元。我們的全年稅率保持在 14.5% 至 15.5% 之間不變。我們假設流通股數量約為 25.5 億股。總而言之，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 月中旬匯率計算，外匯帶來的增量阻力約為 0.05 美元，但中間值仍增加了 0.07 美元，導致全年外匯帶來的負面影響超過 0.30 美元。

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.

當您考慮模型時，需要記住一些事項。我們銷售指引的成長是由我們目前產品組合的強勁表現推動的，其中以 KEYTRUDA 為首，該產品組合因額外適應症和患者需求而持續增長。對於 GARDASIL 來說，第二季（美國除外）的成長將受到向中國出貨時間的不利影響。今年，我們預計對中國的季度出貨量分佈更加均勻。回想一下，2023年，我們從下半年到上半年加快了出貨量，這主要影響了第二季。從短期和長期來看，我們對保護更多人免受 HPV 相關癌症並推動 GARDASIL 成長的能力充滿信心。

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肺炎 (COVID-19) 浪潮的推動。 LAGEVRIO 仍然是某些 COVID-19 患者的重要治療選擇。因此，我們繼續預計全年銷售額將低於去年。繼 WINREVAIR 最近獲得 FDA 批准後，我們很高興為成人肺動脈高壓患者提供一種新的治療選擇。我們看到患者團體和一系列相關處方者對此表現出濃厚的興趣。我們在實現准入方面也取得了良好進展。

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符合標籤和 STELLAR 研究標準的承保政策，而其他付款人正在製定其政策。隨著我們的前進，我們打算提供適當的透明度，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，這符合我們先前的預期，並期待提供最新進展。

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。我們將優先投資於我們的業務，以推動近期和長期成長。我們將繼續投資我們的創新管道，包括針對多個新候選藥物啟動許多新的後期臨床試驗，其中每一個都有可能有意義地解決重要的未滿足的醫療需求。我們仍然致力於支付股息，並計劃隨著時間的推移增加股息。透過業務發展為我們的產品線添加令人信服的科學仍然是重中之重。鑑於我們強大的投資等級信用評級和現金流，我們保持充足的能力來追求更多科學驅動的增值交易。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，在全球對我們的創新藥物和疫苗以及我們卓越的產品線的需求的推動下，我們對我們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。我們卓越的執行力和對創新的持續投資將使我們能夠為現在和未來的患者、客戶和股東創造價值。有了這個，我現在想把電話轉給迪恩。

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，我們的產品線持續穩定取得臨床監管里程碑的進展。今天，我將提供我們的心臟代謝疾病組合、愛滋病毒和疫苗計畫的最新信息，並以我們的腫瘤學管道的進展作為結束語。正如Rob 和Caroline 指出的那樣，上個月末，我們的WINREVAIR 獲得了FDA 的批准，這是我們一流的活性和信號抑製劑，用於治療肺動脈高壓患者，以提高運動能力、改善WHO 功能等級並減少肺動脈高壓。

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向改變許多 PAH 患者的治療歷程的目標邁出了重要一步。歐洲藥品管理局目前正在審查 WINREVAIR，預計今年下半年做出決定。分別評估晚期疾病患者和早期疾病患者的 III 期 ZENITH 和 Hyperion 研究以及評估 WHO II 組肺動脈高壓（一種左心疾病）的 II 期節奏試驗正在進行中。

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（我們的吸入可溶性鳥苷酸環化酶刺激劑）的II/III 期標誌PAH 研究的II 期隊列結果以及WINREVAIR 的STELLAR 試驗結果，我們做出了決定將 MK-5475 的開發重點放在與 COPD 相關的 WHO 3.1 組肺動脈高壓上，而不是在 PAH 上進一步進行。 PH-COPD 是一個急需解決的領域，目前尚無批准的具體療法。我們的愛滋病毒研發管線持續推進。上個月，在關於逆轉錄病毒和機會性感染的會議上的發言，強化了我們在開發管理和治療愛滋病毒的頻率較低的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.

我們相信這些計劃有可能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，一項II 期研究公佈了安全性和有效性結果，該研究評估了每週一次的islatravir 口服組合，這是一項針對核苷逆轉錄酶易位抑製劑和Lenacapavir（一種用於治療成人的一流衣殼抑制劑）的研究感染愛滋病毒。 24 週時，該試驗達到了主要終點，且次要終點保持了較高的病毒抑制率。其他長期數據將在稍後提供。

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，這是來自2 項I 期試驗的新型口服NRTTI 候選藥物，這些試驗評估了18 至55 歲未感染HIV 的成年人的單劑量和多劑量遞增情況。 MK-8527 正在被研究作為 HIV 暴露前預防的潛在每月選擇。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。我們的研究性 21 價肺炎鏈球菌結合疫苗 V116 的多項 III 期試驗的結果已在上個月的國際肺炎和肺炎球菌疾病學會會議上公佈。 V116 已被證明對該疫苗涵蓋的​​所有 21 种血清型均具有免疫原性，其中包括未接種過肺炎球菌疫苗的成年人和經歷過疫苗接種的成年人以及肺炎球菌疾病風險較高的人群。如果獲得批准，V116 將成為第一種專門針對導致 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 首次獲得批准以來，已經產生了穩定的臨床和現實世界證據，支持對男性和女性預防某些人類乳突病毒相關癌症和疾病的良好功效、有效性、安全性和長期持久性。儘管 HPV 疫苗接種已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，要幫助提高疫苗接種率，還有更多工作要做。

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，就女性發病率和死亡率而言，子宮頸癌是全球第四大常見癌症，也是37 個國家（主要是撒哈拉以南非洲、南美洲和東南亞地區）癌症死亡的主要原因。在上個月的泌尿會議上，我們披露了在GARDASIL 開發的基礎上開展一項新的臨床計劃的計劃，以確定一種新型多價HPV 候選疫苗，該疫苗有可能擴大對更廣泛HPV 類型的保護。這包括已知對非洲和亞洲人口以及非洲和亞洲血統個人產生不成比例影響的幾種類型。首次人體研究計畫於今年第四季開始。

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，我們還宣布計劃對 16 至 26 歲的女性和男性進行 2 項隨機、雙盲多年臨床試驗，以檢驗單劑 GARDASIL-9 與目前批准的藥物相比的短期和長期療效以及免疫原性。 3 劑量方案。這些研究的目標是產生數據，清楚證明單劑 GARDASIL-9 是否能提供與核准的治療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.

在腫瘤學方面，我們繼續專注於我們的三支柱策略，包括免疫腫瘤學、精準分子靶向和組織靶向劑。在免疫腫瘤學領域，2024 年 9 月將標誌著 KEYTRUDA 首次獲準用於治療轉移性黑色素瘤十週年。此後，KEYTRUDA 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 聯合化療治療 Figo 2014 II 期至 IVA 子宮頸癌，我們最近宣布關鍵的 KEYNOTE-A18 試驗達到了總體生存的主要終點，可能提供新的生存標準照顧這些病人。我們仍然堅定地致力於提供更好的選擇來預防和治療子宮頸癌。此外，在女性癌症方面，名為 NRG-GY018 的 III 期 KEYNOTE-868 試驗獲得 FDA 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，然後在復發高風險的非小細胞肺癌成年患者中使用 KEYTRUDA 輔助治療。這標誌著歐洲首次批准抗 PD-1 PD-L1 療法作為新輔助治療方案的一部分，隨後根據積極的整體生存結果對可切除的非小細胞肺癌進行輔助治療。

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。在KEYTRUDA 對某些非小細胞肺癌患者取得成功的基礎上，本月早些時候，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 抑制劑，首次與KEYTRUDA 合併使用。進行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，顯示抗腫瘤活性和可控的安全性。 KRAS 是人類癌症中最常見的癌基因之一，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，我們正在快速且嚴謹地推進抗體藥物偶聯物的廣泛管道，並進行多項計劃中和正在進行的 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，我們宣布第一位患者已在II/III 期REJOICE OVARIAN01 試驗中接受給藥，該試驗評估了raludotatug deruxtecan 的有效性和安全性，這是一種研究性CDH6 導向的DXDADC，用於治療鉑類抗藥性卵巢癌患者。我們準備開始一項 III 期研究，評估 ifinatamab/deruxtecan，這是一種針對小細胞肺癌（一種特別難以治療的腫瘤類型）的 B7-H3 靶向 ADC。這些預後仍然不佳的患者迫切需要新的治療方案。

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-6070，一種針對T 細胞接合劑的研究性δ 樣配體3，也在某些類型的小細胞肺癌中進行評估如神經內分泌腫瘤。

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ASCO 舉辦投資者活動，並提供我們的免疫腫瘤學、精準分子和組織靶向藥物的多樣化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 月將是忙碌的一個月，有 3 個監管行動日期，其中包括用於預防侵襲性肺炎球菌疾病和成人肺炎球菌肺炎的 V116。 KEYTRUDA 用於治療原發性晚期或復發性子宮內膜癌； 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.

我們繼續執行我們的策略，專注於卓越運營，並期待提供有關我們全年進展的進一步更新。

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

謝謝你，迪恩。當然，我們已經準備好開始問答了。 （操作員說明）謝謝。

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

（操作員指令）我們的第一個問題來自摩根士丹利的特倫斯·弗林。

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.

這可能是給迪恩的。顯然，你們現在一直專注於建立你的心臟代謝專營權。 sotatercept 的發射正在進行中。您的口服 PCSK9 已處於後期開發階段。我相信，GLP 胰高血糖素也能治療 NASH。但我想我只是好奇你如何廣泛地看待肥胖的機會，因為一方面，它似乎可以與你目前的足跡保持一致。但另一方面，默克似乎更傾向於專業市場，而不是初級保健。所以，迪恩，當你考慮擴建時，也許會喜歡你的想法。

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.

好的，謝謝。是的，我們對心血管代謝的增強感到興奮。您指出了目前知名度最高的程序。但我向您保證，未來幾年您還會有其他項目獲得更多關注。

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.

關於你關於GLP和肥胖的問題，我認為有兩種看待它的方法：你可以從GLP的角度來看它，你可以從肥胖的角度來看它。如果你從 GLP 的角度來看，已經有非常重要的工作顯示了它對糖尿病、減肥、最近對心血管結果、最近對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 relations, 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%.

您是對的，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，將會有不同的人群，無論你稱之為肥胖還是 NASH。由於存在不同的關係，因此提供真正解決主要問題的分子的好處非常重要。這就是我們的策略，例如，在 NASH 領域，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，並且可以減輕 10% 至 12% 的體重。

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。更一般地說，如果你談論的是肥胖問題，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，人們開始思考口腔的耐受性、可及性、組合、如何維持、如何保持肌肉以及其他結果。而同一個分子可能並不是每一個亞群中勝出的最佳分子。所以我想知道，當你說這個詞時，患者群體是否會出現一些分化，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.

我們的下一個問題來自 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工作，特別是 KRAS G12C，這與 Dean 的評論相呼應。所以這個空間變得越來越擁擠。也許請跟我介紹一下您認為您目前的資產與目前已批准的資產或正在開發的泛 KRAS 資產有何不同。

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。所以這是我最喜歡的項目之一。所以我很感激你真的問了這個問題。當你觀察 KRAS 時，正如你所指出的，它是多種癌症中最重要的驅動突變之一。如果你更廣泛地說，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 相關，這僅佔所有 KRAS 突變和所有 RAS 突變的一小部分。但 KRAS G12C 尤其突出的是非小細胞肺癌。根據百分比，該患者佔該患者群體的 12% 到 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，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IO。您需要一種具有 KRAS 的強效化合物才能將其轉移到第一線。這就是我們正在嘗試玩的遊戲。所以很擁擠。但您正在尋找的是一種具有巨大單一療法功效的有效化合物。但最重要的是，當您將其與 pembro 等藥物結合使用時，您可以維持劑量，並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 組合為 71%。這就是我們推進這一目標的原因。

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.

我們的競爭是把它放在一線，然後考慮其他 KRAS 適應症和 IO 敏感/不敏感以及肺癌領域正在出現的其他分子。其中一些與抗體藥物偶聯物有關。因此，我們對 KRAS G12C 專案 1084 感到非常興奮，該專案即將進入第三階段。

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.

也許將重點放在您不經常強調的領域的管道上，特別是免疫學。然後是你在中樞神經系統中談論的許多發現工作。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，就像第二階段一樣。

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 CNS，您強調了有多少人在進行發現研究。您對您在 CNS 的工作分配有何看法？因此，只有兩個領域在新聞稿中沒有強調，但我認為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，我將首先接觸免疫學，特別是 TL1A 領域。因此，TL1A，我們認為它將是非常有效的——更高的功效，而且不僅僅是在功效方面，在耐受性方面。潰瘍性結腸炎計畫第三期已經開始並正在招募。我們希望能夠在接下來的幾個月內宣布 III 期臨床試驗的啟動以及克隆氏症患者的到來。因此，我們非常興奮地熱切地、適當地積極地將 TL1A 轉移到 III 期，以真正勾勒出我們所看到的 TL1A（特別是我們的化合物）的真正差異化概況。

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.

我還應該強調的是，我們不僅在發炎性腸道疾病中研究 TL1A，而且對其他疾病也感興趣。 TL1A 真正有趣的事情之一是它可以阻止發炎。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，纖維化是一個非常重要的組成部分。我們將會有興趣看到這些。我們還有其他資產在推進，包括從 Prometheus 收購中獲得的 TL1A 以外的資產，以及與 Alacrity 一起推進的其他內部資產。

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.

在神經科學方面，我們希望透過 MK-8189 獲得讀數。我們還有其他項目正在推進和推進。我們從 BD 的角度在早期發現領域做出了一些承諾，以加速我們已經公開的一些工作。

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.

我認為在接下來的 1 到 2 年內，我們將看到 Phase IIbs、Phase Is 轉向 Phase II 的讀數。但我認為到那時，我們將能夠更充分地交談。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出發，您必須從經濟價值到醫療保健系統和人口列出。特別是在美國，神經疾病仍然是一個非常重要的地方，我想說的神經疾病不僅是退化性的，而且不僅是經典的神經疾病，而且在精神病學領域也是如此。您已經看到其他人在該領域推動了業務發展。我們有興趣繼續在那裡進行業務開發，但同樣重要的是，移動我們自己的內部項目，主要項目是 MK-8189。

Our next question from Daina Graybosch.

我們的下一個問題來自戴娜·格雷博斯。

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.

我想請教一些關於肺炎鏈球菌疫苗的問題。您多次提到V116是為65歲及以上的成年人量身訂製的。在 ACIP 會議上，他們討論了針對 50 歲或以上成年人的一項建議。我想知道您是否可以評論一下您認為 ACIP 建議最終對 V116 的影響。在 V117 上，我想知道您是否可以談談堆疊場景（我相信現在處於第一階段）是如何為兒科患者量身定制的。

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。當你看看我們對 V116 的了解時，我們仍然相信 - 如果你看看其背後的數據強度，我們已經討論過 - Dean 提到了一些已經出現的臨床讀數。但請記住，我們涵蓋了 83% 的成人血清型致病疾病。這比 PCV20 高 30%。所以它很重要，這就是它的專門設計方式，針對成人疾病中最常見的血清型。

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。如果考慮成本效益，這將是一種非常划算的疫苗。因此，我認為這就是為什麼您開始看到 ACIP 詢問有關 50 至 65 歲年齡層以及 65 歲以上年齡層的問題。

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.

因此，我不想領先 ACIP 及其建議。但我想說，我們對數據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念是重要的。總體而言，我預計我們將看到 ACIP 的廣泛覆蓋範圍。

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。我想再次補充一點，我們希望尊重 ACIP 和 FDA。但你確實指出了一些我認為我們顯然注意到的事情。當 Rob 談到 83% 與 50% 和 30% 以上，以及您所問的具體問題（50 歲到 64 歲）時，我想提醒大家，以前曾考慮過在其他疫苗中降低普遍接種疫苗的年齡。他們無法認為基於成本效益等因素這是一個好主意。透過將其從 50% 增加到 83%，我們相信我們改變了計算方式，這就是為什麼人們對基於 V116 更廣泛的覆蓋範圍而降低該年齡重新產生興趣。

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.

Daina，我認為您還有第二個問題是關於 V117 的。我可能會給出一個籠統的答案，顯然，如果你看一下 V116 的策略，它與 V117 的策略相同：我們如何開發一種研究性 PCV 疫苗，專門針對那些導致疾病的血清型兒童、兒童，希望不會造成不良影響。所以這是一個遵循這模式的模型。我們沒有提供任何關於其他血清型或我們的想法的細節。但只要明白，如果你看V116的型號，V117在peds中是一樣的。

Our next question comes from James Shin with Deutsche Bank.

我們的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層面的指導，但鑑於 WINREVAIR 的重要性和投資者的關注，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 Dean，我想一般來說是精準腫瘤學。但該領域是否知道（聽不清楚）FRalpha 之間有多少重疊？然後對於 patritumab，我知道 HER3 的數據顯示晚期患者中高表達，但在晚期領域有許多進展。那麼默克公司如何設想 patritumab 的定位或定序呢？

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。詹姆斯，也許我會開始。謝謝你的提問。不幸的是，簡短的回答是，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 年的貢獻者是什麼。

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，我認為提出幾點很重要，以便您了解我們如何看待它。首先，我們非常高興能為 PAH 患者提供這種新穎的治療方法。如您所知，我們認為這將改變該領域的遊戲規則。我們為發布做好了充分的準備。我可以告訴你，雖然發佈時間還很早，但到目前為止進展順利。我們已經看到越來越多的處方被開出。我們看到了重複的處方，這既來自 COE 領域，來自卓越中心（美國大約有 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.

我們已經開始向患者家中出貨。希望我們很快就能讓病人接受給藥（如果還沒有的話）。

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.

然後我想我要注意的另一件事是處方者和地點都來自卓越中心，也來自非 COE。所以這是需要注意的事情。最後，從付款人的角度來看，我們看到了良好的訪問權限。沒有真正的限制。事實上，我們已經有幾個付款人制定了承保政策。我認為正如卡羅琳在準備好的評論中指出的那樣，這與標籤和我們在 STELLAR 中看到的非常一致。但事實上，我們看到政策推出後這麼快就為患者提供了保險，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。但到目前為止一切看起來都很好。所以我們對成功發射的信心沒有改變。我們仍然認為這符合我們的預期。隨著我們的前進，我們將為您提供適當的透明度。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.

Dean，我讓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，我將添加一點與 WINREVAIR 的關係。我認為重要的是要強調，我們擁有的適應症或標籤是廣泛的適應症，並且基於 STELLAR。潛在的數據流將繼續為該領域提供資訊並加強其實力。我們有 STELLAR 和 SOTERIA，這是開放標籤。我們有 ZENITH，它是先進的，它將關注死亡率和發病率；還有 HYPERION，它處於旅程的更早階段。

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.

我們將在 2024 年下半年採取歐洲行動。與此相關的是，將會有對創新的需求，我們希望提供這種創新，因為這在自我管理的角度中得到了更多的應用。

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.

您問了很多問題，其中許多問題都相關，其中一些問題被模糊了，但其中一些與卵巢有關，但更廣泛地說，與組織靶向和 ADC 有關。所以我只給你一個概述。當我們觀察這個領域時，我們會觀察有 IO 和化療以及這種組合的癌症。我們會在哪裡看到這一點？我們問自己，能否將 IO 劑與化療劑結合？我們考慮了 KEYTRUDA，但我們也考慮了下一代組織靶向 IO 製劑，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，我們想到化療，我們想到像 RAS 這樣的精準靶向，它們如何結合？我們也從 ADC 的角度來思考。您所談論的具體案例是 HER3 patritumab。 EGFR 非小細胞肺癌正在取得進展。在 B7-H3 中，有關於小細胞肺癌（可能是前列腺癌）的重要數據。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合作夥伴的初始數據對我們來說是驚人的。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，您會考慮生物標記。但對於 CDH6 來說，對各種生物標記子集的影響相當令人印象深刻。因此，我希望這能為您提供一個整體結構，我們很高興——並且非常感謝您提出這個問題。

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.

我只是想考慮一下你們的下一代 HPV 疫苗。我想，我們應該如何考慮新的廣譜 HPV 重新接種機會的潛在滲透率，特別是對於已經服用 GARDASIL 9 的患者。

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

重新接種疫苗和與 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.

有了G9+。我很難回答你的問題，因為我首先要做的是一款性能非常非常好的 G9+。當我明白這一點時，那就太好了，因為我認為有一些患者群體會得到很好的服務。但我還要強調，我們剛剛討論了癌症。我們討論了早期癌症。這是您可以真正治療並有可能治癒的時期，但我們也致力於預防癌症。

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，您需要一種疫苗，例如斯堪的納維亞半島的數據，可以將癌症事件減少 90% 以上，減少 90%。然後是最近的美國癌症協會。我們想知道，如果你們製造 G9+ 疫苗，你們是否可以提出論點，我們的 G9+ 是否成功，以及我們希望實現的目標，你們是否可以從根本上改變人們建議女性進行與子宮頸癌相關的癌症篩檢的方式癌症，以及減少男性和女性罹患子宮頸癌以外的許多其他癌症的機會。

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。我想補充一點，當我們今天坐在這裡時，我們都知道世界上有很多很多人沒有接種疫苗來預防、幫助保護他們免受 HPV 相關癌症的侵害。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，特別是針對不同的族群。我們將根據疫苗提供的益處適當定價。因此，我們期待繼續看到 GARDASIL 的成長，並了解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沃爾夫研究公司的蒂姆·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?

我有一些關於 KEYTRUDA subcu 的問題。它可能在科學上並不性感，但當然，它可能具有相當的商業意義。我相信，我們將在今年稍後看到這些數據。該讀數有任何風險嗎？或者我們可以認為它是一個灌籃嗎？

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 subcu 何時在美國推出（大概是明年），採用速度會快或慢，還是介於兩者之間？最終，一個 subcu 可以在數量或病患數量上佔特許經營權的多少？

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 D770, we will be sharing that data by early 2025.

所以我將討論第一部分。我提醒自己，一旦將創新藥物植入患者體內，就沒有什麼是一勞永逸的了。所以我會回答這個問題。但我認為您確實強調了我們正在推進的 pembro 加透明質酸酶。我有點不同意。我確實認為它在某些方面很性感。對於 D770，我們將在 2025 年初共享該數據。

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...

我認為這確實是一項重要創新的原因是真正增加了存取權限。您已經看到了 pembrolizumab 和 KEYTRUDA 帶來的早期癌症讀數的數量，尤其是在早期階段，當我們談論 KEYNOTE-671 時，當我們談論腎細胞癌時，我們有 OS 獲益。我認為這對患者來說非常非常重要。它對於接受治療的患者也很重要，特別是對於那些接受單一療法的患者，尤其是那些與口服藥物聯合治療的患者，因為它使治療變得更加容易。因此，我們認為這是一個重要的計劃，它可能會對患者及其獲得 PD-1 的機會產生重大影響，因為我們了解 PD-1 的基本要素。而在財務方面...

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。蒂姆，也許我會就您關於吸收率以及這可以佔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，我們確實看到了——它始於 IO 製劑本身的臨床數據的強度。所以更多的是他們對 KEYTRUDA 的信心。其次，它是關於交付機制，這很重要，因為我們考慮明顯利用我們擁有的數據以及 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.

但我會告訴你，當我們考慮在推出時提前推出這項功能時，我們的目標將是適當的價格，以推動快速採用。因此，我們確實希望看到採用，並且我們確實認為您會看到它。顯然，如果你看看到 2028 年，如果我們看看接受 KEYTRUDA 單一療法的患者、口服聯合療法的患者和聯合使用通過我們的KEYTRUDA 的一些輔助和新輔助領域進入疾病的早期階段，這代表了當時患者群體的約50%。因此，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 and share 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.

潛在地，我們並沒有排除研究轉移環境和在機構內以及在機構外轉移的人接受護理的人的機會。但顯然，對病人的價值在於易用性，能夠在醫院環境之外使用它。如果您使用 subcu 與 IV 相比，時間和份額顯然會更少。然後，從醫療保健系統的成本來看，我們認為，能夠不讓病人長時間坐在椅子上，讓更多的病人通過，實際上可以推動就診並改善護理的提供。因此，我們認為從患者的角度和提供者​​的角度來看它都是有益的，這就是為什麼我們確實認為當我們提出這種重要藥物時，您會看到它被採用。

Our next question comes from Louise Chen with Cantor.

我們的下一個問題來自 Louise Chen 和 Cantor。

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

我只是想問一下您在 6 月 3 日舉行的 ASCO 會議。

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.

我認為只會有資料流。將會有後續行動和一系列主題演講，無論是胃癌、肝細胞癌、膽道癌、膀胱癌或非小細胞肺癌。我認為您將開始在臨床試驗網站上看到許多項目的討論，這些項目與您熟悉的分子相關的一系列 III 期相關，但也包括以下分子：我們在III 期開發的早期階段，從bomedemstat 到KRAS 計劃，再到許多ADC 以及我們展示的更新，不僅與第一三共ADC 相關，還與其他ADC 相關，無論是TROP2 Claudin 還是（聽不清楚）。因此，您將對這些化合物進行全面的討論，有些是在 ASCO 上，有些是在 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。我知道我們還有幾個人在排隊。我們將額外花 5 到 10 分鐘來回答盡可能多的問題。

Our next question comes from Trung Huynh with UBS.

我們的下一個問題來自瑞銀集團的 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 (UBS) 的 Trung Huynh。關於 WINREVAIR 的發布，感謝您今天就訪問和覆蓋範圍發表的評論。批准後，您注意到 2/3 的 PAH 患者可能會選擇 D 部分和第三個商業廣告。也許您可以擴展您希望啟動的免費援助計劃？您認為今年 D 部分患者中有多少比例可以獲得免費產品？

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。我很欣賞這個問題。正如您所指出的，我們非常注重確保患者獲得藥物。我們非常致力於此。這就是為什麼我們確實有——除了我們要運行的正常程式之外，我們確實有我們正在運行的存取程式。該計劃實際上獨立於我們的商業運營。我們並沒有真正報告由此產生的數據，因為它是透過一個單獨的基金會運作的，坦白說，其目標是確保患者在那裡獲得藥物。所以這是可用的。您可以在我們的網站上訪問它，我們致力於確保患者獲得藥物。但具體細節我們不打算討論。

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.

也許在您使用 Moderna 的個人化癌症疫苗上，隨著 III 期試驗接近完成註冊，它當然會引發一個問題，即是否可以根據現有數據對文件進行排序。您能否向我們介紹一下您的想法以及您是否認為您仍然需要第三階段數據或製造會妨礙提前提交？任何幫助將不勝感激。

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 I&T 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 and leases pre-existing immunity, which is KEYTRUDA.

是的，我會接受的。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 I&T 計劃的令人興奮之處以及我們與 Moderna 合作的興奮之處。所以在這裡，我們正在誘導和誘導某種免疫力。我們將其與一種眾所周知的藥物混合，這種藥物可以提供預先存在的免疫力，這就是 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.

我們手中擁有的是一項隨機、早期 IO 敏感試驗，該試驗非常清楚 INT 成分的貢獻，不是免疫原性，而是臨床益處。因此，我只想強調我們的數據，就像人們查看其他人的數據一樣。

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，我們正在將其推進到輔助黑色素瘤和輔助非小細胞肺癌的III 期，並且我們有能力快速而嚴格地推進這一進程，同時招募患者，進展順利，我認為這將是非常好的。這就是我們關注的重點。

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 敏感腫瘤，例如腎細胞癌。我只想強調與耐用性相關的數據強度正在得到解答。我們是否有能力開展這些試驗並成功推進它正在進行解答。顯然，我們還需要與我們的同事合作，我們對他們在製造方面所做的工作深表敬意。

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，他們確實挑戰了極限。我們這樣做的能力對於使其成為一種重要的治療方法非常重要。至於 FDA 的決定， 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.

我們的下一個問題來自摩根大通的克里斯·肖特。

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?

只是幾個關於 GARDASIL 的問題。您指出，今年中國的銷售分佈更加均勻，第二季的比較似乎更加艱難。但您能否直接談談 GARDASIL 今年更廣泛的成長？我想它的核心仍然是你今年的健康成長資產。關於 GARDASIL 的第二個問題是，如果我們轉向單劑 GARDASIL-9，這對特許經營的商業和銷售角度意味著什麼？

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，這是卡洛琳。因此，就 GARDASIL 的分階段而言，正如您所指出的，2023 年期間，我們在中國看到出貨量從下半年到上半年加速，特別是到第二季度。這樣做的結果是，它為中國第一季的營收成長提供了實際的推動力，但它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，考慮到我們在世界各地的疫苗接種水平，考慮到我們一直在擴大的生產規模，我們對在 2024 年繼續推動增長的能力充滿信心。到我們的製造能力不受限制，從而使我們能夠進一步供應和支持市場。

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，我們的成長機會是巨大的，因為我們希望繼續提高青少年疫苗接種率，因為我們希望改善中性疫苗接種，因為我們希望真正激活中成人市場，但越來越多地進入低收入和中等收入市場，這將有不同的價格點。

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 be 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.

當我們今天坐在這裡時，繼續對 GARDASIL 的近期和長期前景充滿信心。當我們研究單劑量 GARDASIL 的可能性時，我們正在進行的研究將是一項全面的研究，需要一些時間才能展開。目前我們在市場上看到的是，某些低收入市場正在實施單劑量方案，他們也透過擴大年齡層或在現階段選擇接種男性來增加接種人數。我們必須從長遠來看單劑疫苗的數據如何發揮作用，以確保我們根據我們帶來的好處對疫苗進行定價，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 Luisa Hector 和 Berenberg。

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 的發布也有疑問。我只是想檢查皮下注射有多簡單以及您何時可能期望啟動自動注射器。另外，我們是否真的應該期望 D 部分的訪問以與商業類似的速度上線？我只是不確定這是否會推遲到明年。

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，明年 D 部分重組的價格。當這種情況發生時，您期望付款人如何表現？我可以看到，支付者將為更高價格的口服療法承擔更大的負擔。您是否預計實際藥物中會出現一些阻力，導致您屆時會獲得更高的回扣？或者您認為付款人的增量負擔可能會更廣泛地分佈在所有產品上？這是 WINREVAIR 關注的一個更宏觀的問題。

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.

這就是迪恩。我將回答您有關 WINREVAIR 交付方面的問題。我們將其裝在小瓶中，並且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使用它。我們相信，隨著時間的推移，絕大多數人都會將其用作自我管理。這是一個非常習慣注射的患者族群。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，需要進一步的創新，而自動注射器將至關重要。我們現在正在進行研究，以評估我們如何提供這樣的選擇，我們希望在不久的將來將這些選擇和計劃更加公開。但我們完全同意您的觀點，即未來的自動注射器將很重要。

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。在這個階段，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政策均等覆蓋。因此，隨著我們前進，我們將期待在所有這些領域為盡可能多的患者提供幫助，無論其覆蓋範圍如何。

Our next question comes from Seamus Fernandez with Guggenheim.

我們的下一個問題來自古根漢的謝默斯·費爾南德斯。

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.

我想實際詢問一下你們的 RSV 標靶抗體，你們對此有何看法，其選擇性、市場規模以及默克在該市場的潛在參與度，因為這與競爭對手目前的全球供應限制有關。似乎更積極或盡可能積極地進入市場實際上可以為默克帶來有意義的市場機會。

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，我想聽聽您在三、四年來思考業務演變時的定性觀點。 2028-2029 年對 KEYTRUDA 來說仍然是一個有意義的挑戰。但當你展望今年剩餘時間並進入 2025 年時，從收購的規模和類型來看，業務發展對默克來說有多重要，我認為投資者肯定對默克去年的執行表示讚賞。後期資產。

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。那我將回答 RSV 問題。所以clesrovimab，我們對此感到興奮。正如許多人所知，它是一種單株抗體，是使嬰兒獲得被動免疫的一種方法。正如我們最近所看到的，我們認為這非常重要。我認為，我們的產品是單一固定劑量，並且具有覆蓋整個 RSV 季節的耐久性，這一點至關重要。以及隨時給嬰兒注射疫苗的能力，以及其他替代策略，例如孕產婦疫苗接種。

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，我們相信這將是一種傑出的單株抗體，並且具有很高的抗藥性屏障。因此，我們很高興能夠看到這些數據，並以速度和嚴謹的方式將其推向市場，因為我們認為這將是一個重要的貢獻者，特別是考慮到我們在剛剛過去的RSV 季節中看到的情況季節。

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.

我確實想藉此機會說，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（一種減毒活四價疫苗）在媒體上廣為人知。我們同樣熱切地希望將其推進到第三階段，因為我們已經看到了布坦坦研究所同事關於這種疫苗的有效性和功效的數據。

But I'll turn it back to Rob.

但我會把它轉回給羅布。

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，我想，如果我想稍微思考一下我們過去三年的處境，我想提出幾點。第一，我認為我們在相對較短的時間內取得了巨大的進步，我將所有的功勞歸功於迪恩和我們的研發同事，他們所做的一切以及他們如何能夠真正完美地行動通過我們的管道生產的產品。令人驚訝的是，三年過去了，我們還沒有遇到任何重大失敗。服用 islatravir 後可能會打嗝，但這種情況又會回來。因此，我對我們研發部門的同事所做的事情感到非常自豪。

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、製造角度思考，我們正在推動產品，我們正在展示價值。我們已準備好推出 WINREVAIR，這一事實表明我們可以如何快速建立能力。我們在 KEYTRUDA 中做到了這一點，我們在 JANUVIA 中做到了這一點，現在我們在 WINREVAIR 中做到了這一點，我們將在未來的新領域中做到這一點。所以我們對此感覺非常好。因此，在研發、商業、製造等所有要素中，業務都在交付。

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.

因此，當我們今天坐在這裡時，如果我們的臨床成功繼續下去，我認為隨著時間的推移，您將看到我們擁有比我們多年來（如果有的話）更加多樣化的成長動力。這非常重要。這一切確實導致了你在其他場合聽到我表達的信心，我越來越不關注 2028 年。美國是 2028 年；在中國，是2031年；在中國，是2031年。 2032 年在歐洲和日本。所以這不是一瞬間的事件。它實際上是隨著時間的推移而發生的。

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 left with a great team.

但話雖這麼說，正如你聽到我說的那樣，我認為它更像是一座小山而不是懸崖。我非常有信心在那之後我們會以快速成長的方式回歸。目前我們非常關注 2030 年至 2040 年的永續發展引擎。所以我對我們現在的處境感覺很好，但我只是想強調這是團隊努力的結果，我現在擁有一支優秀的團隊。

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 Seamus，也謝謝大家今天抽出寶貴的時間和興趣。我希望在 6 月 3 日舉行的 ASCO 活動或本季我們將參加的一些會議上見到你們中的許多人。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。此時，您可以斷開線路。