默克藥廠 (MRK) 2022 Q1 法說會逐字稿

Good morning. My name is Grace Lakra, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Merck & Co. Q1 Sales and Earnings Conference Call. (Operator Instructions) Thank you. I would like to turn the call over to Peter Dannenbaum, Vice President of Investor Relations. Please go ahead.

早上好。我的名字是 Grace Lakra，今天我將成為您的會議接線員。在這個時候，我想歡迎大家參加默克公司第一季度銷售和收益電話會議。 （操作員說明）謝謝。我想把電話轉給投資者關係副總裁 Peter Dannenbaum。請繼續。

Thank you, Grace, and good morning. Welcome to Merck's First Quarter 2022 Conference Call. Speaking on today's call will be Rob Davis, President and Chief Executive Officer; Caroline Litchfield, Chief Financial Officer; and Dr. Dean Li, President of Merck Research Labs.

謝謝你，格蕾絲，早上好。歡迎來到默克公司 2022 年第一季度電話會議。在今天的電話會議上發言的將是總裁兼首席執行官 Rob Davis； Caroline Litchfield，首席財務官；默克研究實驗室總裁李院長博士。

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 items from our non-GAAP results and provide a reconciliation in our press release.

在我們開始之前，我想指出一些項目。您會看到我們的 GAAP 結果中有項目，例如與收購相關的費用、重組成本和某些其他項目。您應該注意，我們已將這些項目從我們的非公認會計原則結果中排除，並在我們的新聞稿中提供了對賬。

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 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的安全港條款含義內的前瞻性陳述。這些陳述是基於當前的信念做出的默克管理層，並受到重大風險和不確定性的影響。如果我們的基本假設被證明不准確或不確定性成為現實，實際結果可能與前瞻性陳述中所述的結果大不相同。

Our SEC filings, including Item 1A in the 2021 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.

我們向美國證券交易委員會提交的文件，包括 2021 年 10-K 中的第 1A 項，確定了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陳述中預測的結果存在重大差異的某些風險因素和警示性陳述。默克不承擔公開更新任何前瞻性陳述的義務。

During today's call, a slide presentation will accompany our speakers' prepared remarks. The presentation, today's earnings release as well as 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。演示文稿、今天的收益發布以及我們提交給美國證券交易委員會的文件均已發佈到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 Rob。

Thanks, Peter. Good morning, and thank you for joining today's call. Before I get started, let me take a moment to speak about the ongoing crisis in Ukraine.

謝謝，彼得。早上好，感謝您加入今天的電話會議。在開始之前，讓我花點時間談談烏克蘭目前的危機。

We're hopeful for an immediate and peaceful resolution to the Russian invasion of the country, and we support the Ukrainian people and stand with them, and recognize what a terrible tragedy this represents. Merck is making every effort to protect the health and safety of our employees and to ensure essential medicines and vaccines continue to reach patients. In addition, we are dedicating meaningful resources to address the humanitarian crisis in the country through multiple channels.

我們希望立即和平解決俄羅斯對該國的入侵，我們支持烏克蘭人民並與他們站在一起，並認識到這代表著一場多麼可怕的悲劇。默克正在盡一切努力保護我們員工的健康和安全，並確保基本藥物和疫苗繼續送達患者手中。此外，我們正在投入有意義的資源，通過多種渠道解決該國的人道主義危機。

Turning to our business. We continue to deliver across our key strategic priorities in the first quarter. We're sustaining the strong business momentum we delivered in 2021 with robust top and bottom line growth. We've also achieved significant clinical advancements across our research pipeline and successfully integrated Acceleron.

轉向我們的業務。我們將繼續在第一季度實現我們的關鍵戰略重點。我們將保持我們在 2021 年實現的強勁業務勢頭，實現強勁的營收和利潤增長。我們還在整個研究管道中取得了重大的臨床進展，並成功整合了 Acceleron。

Now moving to our results. We've had a strong start to 2022, achieving very strong top and bottom line growth. Commercially, we continue to execute well across a broad set of key growth drivers most notably, KEYTRUDA, GARDASIL and Animal Health. Our performance reflects robust underlying demand for our derisked innovative portfolio and reinforces the importance of our science-led strategy.

現在轉到我們的結果。我們在 2022 年有一個強勁的開端，實現了非常強勁的頂線和底線增長。在商業上，我們繼續在廣泛的關鍵增長驅動力方面表現良好，尤其是 KEYTRUDA、GARDASIL 和動物健康。我們的業績反映了對我們已去風險的創新產品組合的強勁潛在需求，並強化了我們以科學為主導的戰略的重要性。

LAGEVRIO, our COVID-19 antiviral treatment, was a significant contributor as well. But even excluding these sales, our top line growth was still a very healthy 19% versus last year.

我們的 COVID-19 抗病毒治療 LAGEVRIO 也是一個重要貢獻者。但即使不包括這些銷售額，與去年相比，我們的收入增長仍然是非常健康的 19%。

On LAGEVRIO, we've accelerated broad global access, and it's now established as an important tool for patients and health care providers to address the ongoing pandemic. Since receiving emergency use authorization in December, we've delivered approximately 6.4 million courses to more than 30 countries. The success we are achieving is reflected in our updated 2022 guidance, which demonstrates our expectation for another year of strong growth and overall business momentum.

在 LAGEVRIO 上，我們加速了廣泛的全球訪問，現在它已成為患者和醫療保健提供者應對持續流行病的重要工具。自 12 月獲得緊急使用授權以來，我們已向 30 多個國家/地區提供了大約 640 萬門課程。我們正在取得的成功反映在我們更新的 2022 年指導中，這表明我們對又一年的強勁增長和整體業務勢頭的預期。

Our oncology business is benefiting from the continued rollout of new and important indications, including in earlier lines of therapy. Global demand for GARDASIL remains strong and growth will benefit from increased supply as a result of the significant investments we are making to expand manufacturing capacity, and our Animal Health business remains positioned to grow at above-market rates.

我們的腫瘤業務受益於新的重要適應症的持續推出，包括早期的治療線。全球對 GARDASIL 的需求依然強勁，增長將受益於我們為擴大製造能力進行的重大投資而增加的供應，我們的動物保健業務仍以高於市場的速度增長。

Longer term, we remain confident in our ability to deliver strong revenue growth and operating margin expansion through 2025. We're preparing for the post-KEYTRUDA LOE period by continuing to strengthen the levers we have and building upon them in order to deliver long-term growth.

從長遠來看，我們仍然有信心在 2025 年之前實現強勁的收入增長和營業利潤率擴張。我們正在為後 KEYTRUDA LOE 時期做準備，繼續加強我們擁有的槓桿並在它們的基礎上提供長期-長期增長。

In oncology, we remain committed to building on the foundational position that we have achieved with KEYTRUDA, and we aim to expand our presence in this key therapeutic area and to establish an enduring leadership position. In addition, we'll continue to maximize the opportunities we see for our durable growth drivers, such as GARDASIL, our pneumococcal portfolio and Animal Health through our proven commercial execution.

在腫瘤學方面，我們將繼續致力於鞏固我們與 KEYTRUDA 取得的基礎地位，我們的目標是擴大我們在這一關鍵治療領域的影響力並建立持久的領導地位。此外，我們將繼續通過我們經過驗證的商業執行，最大限度地利用我們看到的持久增長動力，例如 GARDASIL、我們的肺炎球菌產品組合和動物健康。

Beyond our existing portfolio, business development remains a key priority. We remain highly focused in our pursuit of the best external innovation and will be appropriately aggressive when great science and value align. We have a strong track record of business development, but we know we need to do more. And we believe we are well positioned to quickly deploy capital towards the right strategic assets as they present themselves. And finally, we'll continue to advance our broad pipeline across key therapeutic areas in order to deliver medically important innovations to patients.

除了我們現有的產品組合，業務發展仍然是一個關鍵優先事項。我們仍然高度專注於追求最好的外部創新，當偉大的科學和價值相結合時，我們將適當地積極進取。我們在業務發展方面有著良好的記錄，但我們知道我們需要做得更多。我們相信，我們有能力在正確的戰略資產出現時迅速將其部署到正確的戰略資產上。最後，我們將繼續推進我們在關鍵治療領域的廣泛管道，以便為患者提供醫學上重要的創新。

We've taken important steps to provide increased transparency into the opportunities we see in our portfolio and our business, including through two recent investor events. Earlier this month, we provided a detailed description of our growing cardiovascular portfolio and pipeline. At Merck, we're focusing our efforts where the needs are greatest and where we have the best opportunity to positively impact patients' lives, including in heart failure, pulmonary arterial hypertension, thrombosis and atherosclerosis.

我們已採取重要措施，提高我們在投資組合和業務中看到的機會的透明度，包括通過最近的兩次投資者活動。本月早些時候，我們詳細描述了我們不斷增長的心血管產品組合和管道。在默克，我們將努力集中在需求最大的領域，以及我們最有機會積極影響患者生活的領域，包括心力衰竭、肺動脈高壓、血栓形成和動脈粥樣硬化。

We've made significant advancements across our CV pipeline and believe our broad, differentiated portfolio can have meaningful impacts on patients' lives with at least 8 potential new approvals by 2030. We're confident that these important innovations have the potential to be meaningful growth drivers for Merck well into the next decade.

我們在 CV 管道中取得了重大進展，並相信我們廣泛、差異化的產品組合可以對患者的生活產生有意義的影響，到 2030 年至少有 8 個潛在的新批准。我們相信這些重要的創新有潛力實現有意義的增長默克未來十年的驅動力。

And in February, we hosted our inaugural ESG event which highlighted our activities in our 4 priority areas of access to health, employees, environmental sustainability and ethics and values. Our ESG efforts are grounded in our company's values, and we look forward to building on Merck's legacy of operating responsibly going forward.

2 月，我們舉辦了首屆 ESG 活動，突出了我們在獲得健康、員工、環境可持續性以及道德和價值觀這 4 個優先領域的活動。我們的 ESG 努力以我們公司的價值觀為基礎，我們期待在默克公司負責任經營的傳統基礎上再接再厲。

Before I close, I'd like to take a moment to recognize Dr. Roy Baynes, who has announced his retirement after 8 years at Merck. Roy has been instrumental in helping Merck become a leading oncology company, particularly through his leadership in the development of KEYTRUDA. We wish Roy the best in his future endeavors, and we're confident that he leaves behind an outstanding team and program. I'm pleased to report that Dr. Eliav Barr was appointed to succeed Roy. Eliav not only has deep experience having served in several research capacities throughout his more than 2 decades at Merck, but also has an unwavering commitment to patients, consistent with Merck's purpose to save and improve lives.

在結束之前，我想花點時間認識一下 Roy Baynes 博士，他在默克公司工作了 8 年後宣布退休。 Roy 在幫助默克成為領先的腫瘤學公司方面發揮了重要作用，特別是通過他在 KEYTRUDA 開發中的領導作用。我們祝愿羅伊在未來的努力中一切順利，我們相信他會留下一支出色的團隊和項目。我很高興地報告 Eliav Barr 博士被任命接替 Roy。 Eliav 不僅在默克公司 2 多年的多項研究工作中擁有豐富的經驗，而且對患者有著堅定不移的承諾，這與默克公司拯救和改善生命的宗旨相一致。

In summary, we've begun 2022 with strong operational momentum, and I want to express my sincere thanks to our employees worldwide for their continued focus and commitment. We remain confident in our fundamental strategy, our growth prospects and in our ability to deliver significant benefits for patients and value to shareholders well into the future.

總之，我們以強勁的運營勢頭開始了 2022 年，我要衷心感謝我們全球員工的持續關注和承諾。我們對我們的基本戰略、我們的增長前景以及我們在未來為患者帶來重大利益和為股東創造價值的能力充滿信心。

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

有了這個，我會把電話轉給卡羅琳。

Thank you, Rob. Good morning. As Rob highlighted, we have had a very strong start to 2022 with exceptional performance in both revenues and earnings. These results further demonstrate that our focus on science and innovation at the core of our strategy, enabled by excellent execution of our dedicated colleagues across the globe, is delivering value for patients, customers and investors.

謝謝你，羅布。早上好。正如 Rob 強調的那樣，我們在 2022 年的開局非常強勁，收入和收益都表現出色。這些結果進一步表明，我們專注於戰略核心的科學和創新，得益於我們在全球範圍內敬業的同事的出色執行，正在為患者、客戶和投資者創造價值。

Total company revenues were $15.9 billion, an increase of 50%. LAGEVRIO contributed $3.2 billion in revenues. Excluding LAGEVRIO, the base business delivered very strong growth of 19%.

公司總收入為 159 億美元，增長 50%。 LAGEVRIO 貢獻了 32 億美元的收入。不包括 LAGEVRIO，基礎業務實現了 19% 的強勁增長。

The remainder of my comments will be on an ex-exchange basis. Our human health business continued its strong momentum. Excluding LAGEVRIO, the human health business grew 21%, driven primarily by our key pillars as well as the reduced impact of the pandemic. Our Animal Health business also delivered above-market performance with sales increasing 9%, driven by growth across both companion animals and livestock segments.

我的其餘評論將以交換為基礎。我們的人類健康業務繼續保持強勁勢頭。不包括 LAGEVRIO，人類健康業務增長了 21%，這主要是由於我們的主要支柱以及大流行的影響減少。我們的動物保健業務也取得了高於市場的業績，銷售額增長了 9%，這得益於伴侶動物和牲畜部門的增長。

Now turning to the first quarter performance of our key brands. In oncology, KEYTRUDA grew 27% to $4.8 billion, reflecting continued robust global demand and the expansion into new indications. In the U.S., KEYTRUDA continues to demonstrate strong growth across all key tumors and is benefiting from recent launches in earlier-stage cancers, including triple-negative breast, renal cell carcinoma and melanoma. KEYTRUDA is currently approved to treat 5 indications in earlier-stage cancers, and we are excited about the potential opportunity to expand into adjuvant lung cancer based on the encouraging data from KEYNOTE-091.

現在轉向我們主要品牌的第一季度業績。在腫瘤學領域， KEYTRUDA 增長 27% 至 48 億美元，反映出全球需求持續強勁以及新適應症的擴張。在美國， KEYTRUDA 在所有關鍵腫瘤中繼續表現出強勁增長，並受益於最近推出的早期癌症，包括三陰性乳腺癌、腎細胞癌和黑色素瘤。 KEYTRUDA 目前被批准用於治療早期癌症的 5 種適應症，基於 KEYNOTE-091 令人鼓舞的數據，我們對擴展到輔助肺癌的潛在機會感到興奮。

We continue to be confident that KEYTRUDA's robust clinical data, combined with physicians' familiarity and experience with the product, will support expanded use and patient benefit in early-stage disease. In the metastatic setting, KEYTRUDA continues to maintain its leadership position in non-small cell lung cancer, capturing 8 out of 10 eligible new patients.

我們繼續相信 KEYTRUDA 強大的臨床數據，加上醫生對該產品的熟悉和經驗，將支持擴大早期疾病的使用和患者受益。在轉移性環境中， KEYTRUDA 繼續保持其在非小細胞肺癌領域的領先地位，在 10 名符合條件的新患者中獲得了 8 名。

Outside the U.S., KEYTRUDA's growth continues to be driven by lung cancer and the ongoing launches in head and neck cancer and renal cell carcinoma.

在美國以外， KEYTRUDA 的增長繼續受到肺癌以及頭頸癌和腎細胞癌的持續推出的推動。

Lynparza remains the market-leading PARP inhibitor. Our alliance revenue grew 20%, driven by uptake in metastatic breast cancer. We are also excited by the expanded opportunity in early-stage breast cancer, following the recent FDA approval based on the OlympiA study. Further, we look forward to potentially reaching a broad prostate population based on the PROpel study.

Lynparza 仍然是市場領先的 PARP 抑製劑。在轉移性乳腺癌的推動下，我們的聯盟收入增長了 20%。在最近基於 OlympiA 研究的 FDA 批准之後，我們也對早期乳腺癌的擴大機會感到興奮。此外，我們期待在 PROpel 研究的基礎上可能覆蓋廣泛的前列腺人群。

Lenvima alliance revenue also had very strong growth, driven by uptake following the launches of KEYNOTE-581 in advanced renal cell carcinoma and KEYNOTE-775 in metastatic endometrial cancer, where we are seeing encouraging new patient share trends across each of these tumor types. Lenvima growth also benefited from increased demand in hepatocellular carcinoma in China and certain onetime items.

Lenvima 聯盟的收入也有非常強勁的增長，這得益於在晚期腎細胞癌中推出 KEYNOTE-581 和在轉移性子宮內膜癌中推出 KEYNOTE-775 後的吸收，我們在這些腫瘤類型中看到令人鼓舞的新患者分享趨勢。 Lenvima 的增長還受益於中國對肝細胞癌和某些一次性產品的需求增加。

We are also excited by the launch of WELIREG for patients with certain VHL-associated tumors. WELIREG continues to generate strong interest among scientific leaders, providers and patients. Although still early in its launch, WELIREG has had strong uptake, providing a treatment option to the significant unmet need for these patients. We are working to potentially extend its reach to broader RCC indications in the future.

我們也對針對某些 VHL 相關腫瘤患者推出 WELIREG 感到興奮。 WELIREG 繼續引起科學領導者、提供者和患者的濃厚興趣。儘管 WELIREG 仍處於推出初期，但它已被廣泛接受，為這些患者的巨大未滿足需求提供了一種治療選擇。我們正在努力在未來將其範圍擴展到更廣泛的 RCC 適應症。

Our vaccines portfolio again delivered excellent performance led by GARDASIL, which increased 60% to $1.5 billion. Outside the U.S., significant growth was driven by strong underlying demand across key geographies, particularly China as well as increased supply. In the U.S., sales increased due to the timing of CDC purchases.

我們的疫苗組合在 GARDASIL 的帶領下再次表現出色，增長 60% 至 15 億美元。在美國以外，主要地區（尤其是中國）強勁的潛在需求以及供應增加推動了顯著增長。在美國，由於 CDC 購買的時機，銷售額有所增加。

Global demand for GARDASIL remains robust, supported by strong clinical and real-world data as well as efforts to increase the recognition of GARDASIL as a vaccine that can help prevent certain HPV-related cancers in both females and males.

全球對 GARDASIL 的需求依然強勁，這得益於強大的臨床和真實世界數據以及努力提高 GARDASIL 作為疫苗的認可度，這種疫苗可以幫助預防女性和男性的某些 HPV 相關癌症。

In our hospital acute care portfolio, BRIDION sales grew 20%, driven by the ongoing recovery in surgical procedures during the quarter and continued strong leadership of the neuromuscular blockade reversal agent class.

在我們的醫院急症護理產品組合中，BRIDION 銷售額增長了 20%，這得益於本季度外科手術的持續復甦以及神經肌肉阻滯逆轉劑類別的持續強勢領導地位。

Our Animal Health business delivered another quarter of robust growth, with sales increasing 9%. Companion animal sales increased 13%, driven by global demand in parasiticides, including the BRAVECTO line of products as well as vaccines. Livestock sales increased 7% due to higher demand in ruminants and poultry.

我們的動物保健業務又實現了一個季度的強勁增長，銷售額增長了 9%。伴侶動物的銷售額增長了 13%，這得益於全球對殺蟲劑的需求，包括 BRAVECTO 系列產品和疫苗。由於反芻動物和家禽的需求增加，畜牧業銷售額增長了 7%。

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 70.7%, a decrease of 5.9 percentage points, driven primarily by higher LAGEVRIO sales. As a reminder, we share profits from LAGEVRIO equally with our partner Ridgeback, which is reflected within cost of sales and reduces our gross margin percentage. Gross margin this quarter also reflects the favorable impact of product mix, offset by higher manufacturing costs.

我現在將向您介紹我們的損益表的其餘部分，我的評論將基於非公認會計原則。毛利率為 70.7%，下降 5.9 個百分點，主要受 LAGEVRIO 銷售額增長的推動。提醒一下，我們與合作夥伴 Ridgeback 平等分享 LAGEVRIO 的利潤，這反映在銷售成本中並降低了我們的毛利率百分比。本季度的毛利率也反映了產品組合的有利影響，但被較高的製造成本所抵消。

Operating expenses increased 7% to $4.8 billion as we continue to prudently invest behind our growth drivers and pipeline. Other expense was approximately $140 million. Our tax rate was 14%. Taken together, we earned $2.14 per share.

由於我們繼續謹慎地投資於我們的增長動力和管道，運營費用增加了 7% 至 48 億美元。其他費用約為 1.4 億美元。我們的稅率是 14%。合起來，我們每股賺了 2.14 美元。

Turning now to our 2022 non-GAAP guidance. As a reminder, at the request of the SEC, certain companies in our industry, including ours, have made changes to non-GAAP reporting. We will no longer exclude significant expenses for upfront and milestone payments related to collaborations and licensing agreements as well as transactions accounted for as asset acquisitions from non-GAAP results.

現在轉向我們的 2022 年非 GAAP 指導。提醒一下，應美國證券交易委員會的要求，我們行業中的某些公司，包括我們的公司，已對非公認會計原則報告進行了更改。我們將不再排除與合作和許可協議相關的前期和里程碑付款的重大費用，以及從非公認會計原則結果中計入資產收購的交易。

As a result, $1.7 billion of R&D charges primarily related to the acquisition of Pandion are now included in our recast 2021 non-GAAP results. This increased R&D expense by $1.7 billion and decreased non-GAAP EPS by $0.65. There was no impact to the first quarters of 2021 and 2022.

因此，主要與收購 Pandion 相關的 17 億美元研發費用現在包含在我們重鑄的 2021 年非 GAAP 業績中。這使研發費用增加了 17 億美元，非 GAAP 每股收益減少了 0.65 美元。對 2021 年和 2022 年第一季度沒有影響。

Our 2022 guidance does not assume any significant transactions that would have previously been excluded from non-GAAP. So this could change in the future quarters if we execute business development which is a strategic priority.

我們的 2022 年指南不假設任何以前被排除在非公認會計原則之外的重大交易。因此，如果我們執行作為戰略重點的業務發展，這可能會在未來幾個季度發生變化。

The underlying strength of our business enables us to raise and narrow our full year guidance. We now expect revenue to be between $56.9 billion and $58.1 billion, representing growth of 17% to 19% or 11% to 12%, excluding LAGEVRIO and the impact from foreign exchange. The projected impact from foreign exchange includes an incremental headwind of approximately $200 million using mid-April rates, resulting in a full year negative impact of just over 2%.

我們業務的潛在實力使我們能夠提高和縮小全年指導。我們現在預計收入將在 569 億美元至 581 億美元之間，增長 17% 至 19% 或 11% 至 12%，不包括 LAGEVRIO 和外匯影響。外彙的預計影響包括使用 4 月中旬的匯率增加約 2 億美元的逆風，導致全年的負面影響略高於 2%。

We are increasing our gross margin expectation to between 74% and 74.5%. We expect operating expenses of $20.3 billion to $21.3 billion. At the midpoint, this is consistent with what was implied by our prior guidance. We expect other expense of approximately $350 million. We assume a full year tax rate between 13.5% and 14.5% due to an increase in estimated U.S. taxes to be paid on foreign income. We assume 2.53 billion shares outstanding.

我們將毛利率預期提高至 74% 至 74.5% 之間。我們預計運營費用為 203 億至 213 億美元。在中點，這與我們之前的指導所暗示的一致。我們預計其他費用約為 3.5 億美元。我們假設全年稅率在 13.5% 至 14.5% 之間，因為估計美國對外國收入應繳納的稅款有所增加。我們假設流通股為 25.3 億股。

Taken together, we have increased our expected EPS range to $7.24 to $7.36, representing pull-through of the operational strength from our key pillars and operating expense leverage, offset in part by a slight reduction in the top end of our LAGEVRIO sales assumption, the increase in our tax rate and an incremental 1% headwind from foreign exchange using mid-April rates.

總而言之，我們已將預期每股收益範圍提高至 7.24 美元至 7.36 美元，這代表了我們的主要支柱和運營費用槓桿的運營實力的拉動，部分被我們 LAGEVRIO 銷售假設的高端略微降低所抵消，我們的稅率增加，並且使用 4 月中旬的匯率增加了 1% 的外匯逆風。

As you consider your models, there are a few areas to focus on. First, on LAGEVRIO. We are narrowing the range of our full year guidance to $5 billion to $5.5 billion. We have entered into supply and purchase agreements for approximately 10 million courses of therapy. Since authorization, we delivered 6.4 million courses of therapy, including 5 million in the first quarter. We expect approximately half of the remaining full year revenue from LAGEVRIO in the second quarter.

在考慮模型時，有幾個方面需要關注。首先，在 LAGEVRIO 上。我們正在將全年指導範圍縮小至 50 億至 55 億美元。我們已就大約 1000 萬個療程簽訂了供應和採購協議。自授權以來，我們提供了 640 萬個療程，其中第一季度為 500 萬個。我們預計第二季度 LAGEVRIO 剩餘全年收入的一半左右。

We continue to expect strong annual growth for GARDASIL, especially in ex U.S. markets, including China.

我們繼續預計 GARDASIL 將實現強勁的年度增長，尤其是在包括中國在內的美國以外市場。

Finally, as a reminder, our other revenue line contains several items, including supply sales to Organon, which we began recording upon the completion of the spin-off last year and to Johnson & Johnson for its COVID vaccine. Also included are our revenue hedge and royalties. Other revenue in the first quarter also benefited from approximately $100 million in receipts relating to out-licensing agreements.

最後，提醒一下，我們的其他收入線包含幾個項目，包括對歐加農的供應銷售，我們在去年分拆完成後開始記錄，以及強生公司的 COVID 疫苗。還包括我們的收入對沖和特許權使用費。第一季度的其他收入也受益於與外包協議相關的約 1 億美元收入。

Our capital allocation priorities remain unchanged. First, we will continue to prioritize investments in our business and pipeline to drive near- and long-term growth. We will continue to be appropriately aggressive in augmenting our internal pipeline through strategic business development, and we intend to pursue additional value-enhancing opportunities. We remain committed to the dividend with the goal of increasing it over time. To the extent we have excess cash, we will return it to shareholders through share repurchases.

我們的資本配置重點保持不變。首先，我們將繼續優先投資於我們的業務和管道，以推動近期和長期增長。我們將繼續通過戰略業務發展適當積極地擴大我們的內部管道，我們打算尋求更多的增值機會。我們仍然致力於股息，目標是隨著時間的推移增加股息。如果我們有多餘的現金，我們將通過股票回購將其返還給股東。

To conclude, we remain very confident in the growth of our business, driven by the global demand for our innovative medicines and vaccines. We are in a position of financial and operational strength, and our continued execution will enable us to deliver value to patients and our shareholders well into the future.

總而言之，在全球對我們創新藥物和疫苗的需求的推動下，我們對我們的業務增長仍然充滿信心。我們處於財務和運營實力的地位，我們的持續執行將使我們能夠在未來為患者和股東創造價值。

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

有了這個，我現在想把電話轉給 Dean。

Thank you, Caroline. It is good to be here to provide an update on our progress.

謝謝你，卡羅琳。很高興能在這裡提供我們進展的最新情況。

In the first quarter, we continued to demonstrate progress in our pipeline. We made advances across multiple therapeutic areas, including oncology in both advanced and earlier stages of cancer as well as in cardiovascular disease and vaccines. I will also provide an update on LAGEVRIO.

在第一季度，我們繼續展示我們的管道進展。我們在多個治療領域取得了進展，包括癌症晚期和早期階段的腫瘤學以及心血管疾病和疫苗。我還將提供有關 LAGEVRIO 的更新。

In oncology, we continue to build upon our strong position and execute on our strategy to expand, deepen and extend benefits to patients and diversify our imprint on cancer. This past quarter, we achieved milestones from several tumor types as well as different stages of disease.

在腫瘤學領域，我們繼續鞏固我們的強勢地位，並執行我們的戰略，以擴大、深化和擴大對患者的益處，並使我們在癌症方面的印記多樣化。在過去的這個季度，我們在幾種腫瘤類型以及不同的疾病階段都取得了里程碑式的成就。

Notably, we continue to expand our treatment impact in earlier stages of disease, where we now have 6 approvals from the FDA, 5 for KEYTRUDA and 1 for Lynparza. At the European Society for Medical Oncology Virtual Plenary session last month, data from the KEYNOTE-091 or PEARLS trial, evaluating KEYTRUDA for the adjuvant treatment of patients with stage IB to IIIA non-small cell lung cancer following surgical resection were presented. At an interim analysis, KEYTRUDA has significantly improved disease-free survival in all-comers, one of the study's dual primary endpoint. The trial will continue to analyze the other dual primary endpoint of disease-free survival in patients whose tumors express high levels of PD-L1, which did not meet statistical significance at the time of the planned interim analysis. These latest data provide a strong signal for the benefit of KEYTRUDA in the adjuvant treatment study.

值得注意的是，我們繼續擴大我們在疾病早期階段的治療影響，我們現在獲得了 FDA 的 6 項批准， KEYTRUDA 5 項和 Lynparza 1 項。在上個月的歐洲醫學腫瘤學會虛擬全體會議上，來自 KEYNOTE-091 或 PEARLS 試驗的數據，評估了 KEYTRUDA 對手術切除後 IB 至 IIIA 期非小細胞肺癌患者的輔助治療。在一項中期分析中， KEYTRUDA 顯著提高了所有參與者的無病生存率，這是該研究的雙重主要終點之一。該試驗將繼續分析腫瘤表達高水平 PD-L1 的患者的無病生存期的另一個雙重主要終點，該終點在計劃的中期分析時不符合統計學意義。這些最新數據為 KEYTRUDA 在輔助治療研究中的益處提供了強烈的信號。

Additional ongoing studies in earlier stages of non-small cell lung cancer include KEYNOTE-671, which is evaluating neoadjuvant adjuvant therapy for patients with resectable II, IIIA and IIIB disease; KEYNOTE-867, which is studying stereotactic body radiotherapy with or without KEYTRUDA in adults with unresected stage 1 HER2 disease; and KEYLYNK-012, where we are studying KEYTRUDA in combination with Lynparza in stage III disease.

其他正在進行的非小細胞肺癌早期研究包括 KEYNOTE-671，該研究正在評估可切除 II、IIIA 和 IIIB 疾病患者的新輔助輔助治療； KEYNOTE-867，正在研究使用或不使用 KEYTRUDA 對未切除 1 期 HER2 疾病成人的立體定向全身放射治療；和 KEYLYNK-012，我們正在研究 KEYTRUDA 與 Lynparza 聯合治療 III 期疾病。

Following the approval of KEYTRUDA for the adjuvant treatment of patients 12 years and older with stage IIB or IIC melanoma following complete resection based on KEYNOTE-716, we announced that at a prespecified interim analysis, the study also met its secondary endpoint of distinct metastasis-free survival and showed continued improvement in recurrent-free survival compared to placebo. The data from KEYNOTE-716 reinforces the evidence for KEYTRUDA as adjuvant therapy for appropriate patients with stage IIB and IIC following surgery that help prevent recurrence of disease.

繼 KEYTRUDA 獲批用於基於 KEYNOTE-716 完全切除後的 12 歲及以上患有 IIB 或 IIC 期黑色素瘤的患者的輔助治療後，我們宣佈在預先指定的中期分析中，該研究還達到了其次要終點，即明顯轉移-與安慰劑相比，無復發生存期持續改善。來自 KEYNOTE-716 的數據強化了 KEYTRUDA 作為手術後 IIB 和 IIC 期適當患者的輔助治療，有助於預防疾病復發的證據。

Now similarly, in the earlier-stage setting, along with AstraZeneca, we announced Lynparza was approved by the FDA for the adjuvant treatment of patients with germline BRCA mutations with HER2-negative high-risk early breast cancer previously treated with chemotherapy, either before or after surgery based on the OlympiA study. Further, in women's cancer, we received FDA approval for KEYTRUDA for the treatment of patients with microsatellite instability-high, or mismatch repair-deficient advanced endometrial carcinoma based on new data for KEYNOTE-158. Now this approval is the fourth gynecologic cancer approval for KEYTRUDA and marks the fifth approval derived from the KEYNOTE-158 trial, an innovative trial designed to evaluate the use of predictive tumor biomarkers in patients receiving KEYTRUDA for advanced solid tumors.

現在，類似地，在早期階段，我們與阿斯利康一起宣布 Lynparza 已獲得 FDA 批准，用於輔助治療先前接受過化療的 HER2 陰性高危早期乳腺癌的生殖系 BRCA 突變患者，無論是之前還是之前手術後根據 OlympiA 研究。此外，在女性癌症方面，基於 KEYNOTE-158 的新數據，我們獲得了 FDA 批准 KEYTRUDA 用於治療微衛星不穩定性高或錯配修復缺陷的晚期子宮內膜癌患者。現在，該批准是 KEYTRUDA 的第四個婦科癌症批准，標誌著 KEYNOTE-158試驗的第五個批准，該試驗旨在評估預測性腫瘤生物標誌物在接受 KEYTRUDA 治療晚期實體瘤的患者中的使用。

Next, the prostate cancer. Along with AstraZeneca, positive results were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium for the PROpel trial evaluating Lynparza in combination with abiraterone as a first-line treatment for patients with metastatic castrate-resistant prostate cancer with and without mutations in a group of homologous recombination or therapy. At a planned interim analysis, results showed an improvement in radiographic progression-free survival versus the standard of care. These early results also showed a trend towards improved overall survival. The trial will continue to assess this key secondary endpoint, and we plan to engage with health authorities to discuss the findings with the aim of bringing this important option to appropriate patients.

其次，前列腺癌。與阿斯利康一起，在美國臨床腫瘤學會泌尿生殖系統癌症研討會上公佈了 PROpel 試驗的積極結果，該試驗評估了 Lynparza 與阿比特龍聯合作為一組有或無突變的轉移性去勢抵抗性前列腺癌患者的一線治療同源重組或治療。在計劃中的中期分析中，結果顯示與護理標準相比，放射學無進展生存期有所改善。這些早期結果還顯示出總體生存率提高的趨勢。該試驗將繼續評估這一關鍵的次要終點，我們計劃與衛生當局合作討論調查結果，旨在為合適的患者提供這一重要選擇。

Prostate cancer represents a significant unmet need, and we are continually gaining important insights into the biology of the tumor. We are keen on making an impact for patients with late-stage disease.

前列腺癌代表了一個重大的未滿足需求，我們不斷獲得對腫瘤生物學的重要見解。我們熱衷於對晚期疾病患者產生影響。

Last month, we announced the discontinuation of the KEYLYNK-010 study, evaluating the combination of KEYTRUDA and Lynparza for the treatment of metastatic castrate-resistant prostate cancer. At an interim analysis, this study showed no evidence of superiority to abiraterone and enzalutamide with respect to overall survival and radiographic progression-free survival.

上個月，我們宣布終止 KEYLYNK-010 研究，評估 KEYTRUDA 和 Lynparza 的聯合治療轉移性去勢抵抗性前列腺癌。在中期分析中，該研究未顯示在總生存期和影像學無進展生存期方面優於阿比特龍和恩雜魯胺的證據。

Our attention in metastatic castrate-resistant prostate cancer now shifts to KEYNOTE-921, a study exploring the combination of KEYTRUDA and chemotherapy; and KEYNOTE-641, which is evaluating the combination of KEYTRUDA and enzalutamide.

我們對轉移性去勢抵抗性前列腺癌的關注現在轉移到 KEYNOTE-921，這是一項探索 KEYTRUDA 與化療聯合的研究；和 KEYNOTE-641，它正在評估 KEYTRUDA 和 enzalutamide 的組合。

Outside of the United States, we continue to deliver on our regulatory strategy. Notable actions include positive CHMP opinions for cervical, MSI-high and early-stage breast cancer in Europe and approvals for the combination regimen of KEYTRUDA plus Lenvima for advanced renal cell carcinoma in Japan.

在美國以外，我們繼續實施我們的監管戰略。值得注意的行動包括歐洲對宮頸癌、高 MSI 和早期乳腺癌的積極 CHMP 意見，以及日本批准 KEYTRUDA 聯合 Lenvima 治療晚期腎細胞癌的聯合方案。

And finally, to coincide with ASCO, in early June, we are planning to host an investor event in Chicago. At our recent cardiovascular investor event, we showcased our growing portfolio of programs targeting a range of conditions, including atherosclerosis, heart failure, pulmonary arterial hypertension and thrombosis.

最後，為了配合 ASCO，我們計劃在 6 月初在芝加哥舉辦一次投資者活動。在我們最近的心血管投資者活動中，我們展示了針對一系列疾病的不斷增長的項目組合，包括動脈粥樣硬化、心力衰竭、肺動脈高壓和血栓形成。

Following the completion of our acquisition of Acceleron Pharma, we are making strong progress in advancing the development of sotatercept, a potential first-in-class soluble activin receptor type IIA fusion protein. We recently completed enrollment for the STELLAR trial ahead of schedule. STELLAR is the first of 4 ongoing Phase III studies evaluating sotatercept. This progress reflects enthusiasm from investigators regarding this novel investigational mechanism.

完成對 Acceleron Pharma 的收購後，我們正在推進 sotatercept 的開發，這是一種潛在的一流可溶性激活素受體 IIA 型融合蛋白。我們最近提前完成了 STELLAR 試驗的註冊。 STELLAR 是評估 sotatercept 的 4 項正在進行的 III 期研究中的第一項。這一進展反映了研究人員對這種新型研究機制的熱情。

For the first time, the 2022 American Heart Association, American College of Cardiology and Heart Failure Society of America, guideline for the management of heart failure included Verquvo, which we collaborate on with our partner, Bayer, as a Class IIB recommendation for the treatment of stage C heart failure with reduced ejection fraction. The guideline highlights the submechanism of sGC such as Verquvo and the potential benefits of stimulating soluble guanylate cyclase and increasing cyclic GMP.

2022 年美國心臟協會、美國心髒病學會和美國心力衰竭協會首次將 Verquvo 納入心力衰竭管理指南，我們與合作夥伴拜耳合作，將其作為 IIB 類治療推薦C 期心力衰竭伴射血分數降低。該指南強調了 sGC 的子機制，例如 Verquvo，以及刺激可溶性鳥苷酸環化酶和增加環狀 GMP 的潛在益處。

Based on evidence from the pioneering VICTORIA trial, Verquvo is the first drug specifically studied and approved for patients with worsening heart failure and the only drug recommended in the new guidelines for these patients.

基於開創性 VICTORIA 試驗的證據，Verquvo 是第一種專門研究和批准用於心力衰竭惡化患者的藥物，也是新指南中推薦給這些患者的唯一藥物。

Our ongoing VICTOR study is designed to expand on the evidence to date by evaluating Verquvo in patients with chronic heart failure and reduced ejection fraction who have not experienced a recent worsening heart failure event. Merck is uniquely positioned to meaningfully impact the treatment of patients with cardiovascular disease with at least 8 potential approvals by 2030, including Verquvo and stable heart failure and sotatercept as well as our pipeline of candidates, including an inhaled soluble guanylate cyclase stimulator, a Factor XI inhibitor and an oral PCSK9 inhibitor.

我們正在進行的 VICTOR 研究旨在通過評估 Verquvo 對近期未經歷過惡化的心力衰竭事件的慢性心力衰竭和射血分數降低的患者進行評估來擴展迄今為止的證據。默克具有獨特的優勢，可以對心血管疾病患者的治療產生有意義的影響，到 2030 年至少有 8 項潛在批准，包括 Verquvo 和穩定的心力衰竭和 sotatercept 以及我們的候選藥物，包括吸入可溶性鳥苷酸環化酶刺激劑、因子 XI抑製劑和口服 PCSK9 抑製劑。

Next, the COVID-19 and LAGEVRIO. As the pandemic evolve, there continues to be regional surges in infection rates with the emergence of new COVID-19 variants. Now some of these strains are resistant to specific monoclonal antibody regimens and appear able to evade some vaccine protection, highlighting the importance of testing and the availability of antiviral option.

接下來是 COVID-19 和 LAGEVRIO。隨著大流行的發展，隨著新的 COVID-19 變體的出現，感染率繼續出現區域性激增。現在，其中一些菌株對特定的單克隆抗體方案具有抗藥性，並且似乎能夠逃避某些疫苗保護，這突出了測試的重要性和抗病毒選擇的可用性。

At the recent European Congress of Clinical Microbiology and Infectious Diseases, we presented Phase III virology outcomes data for MOVe-OUT, adding to the growing body of evidence for the antiviral properties of LAGEVRIO.

在最近的歐洲臨床微生物學和傳染病大會上，我們展示了 MOVe-OUT 的 III 期病毒學結果數據，為 LAGEVRIO 的抗病毒特性增加了越來越多的證據。

The PANORAMIC trial evaluating novel antivirals for early treatment, which is being sponsored by the University of Oxford and funded by the U.K. government and the MOVe-AHEAD trial evaluating LAGEVRIO for post-exposure prophylaxis are both ongoing. We are working collaboratively with the European Medicines Agency to provide additional data from these trials in order to secure an approval.

由牛津大學贊助並由英國政府資助的評估新型抗病毒藥物早期治療的 PANORAMIC 試驗和評估 LAGEVRIO 用於暴露後預防的 MOVe-AHEAD 試驗都正在進行中。我們正在與歐洲藥品管理局合作，從這些試驗中提供更多數據，以確保獲得批准。

We remain confident in the safety and efficacy of LAGEVRIO in appropriate patients. In particular, we believe it's low propensity for drug-drug interactions makes it an important option for patients.

我們對 LAGEVRIO 在適當患者中的安全性和有效性仍然充滿信心。特別是，我們認為它對藥物-藥物相互作用的低傾向性使其成為患者的重要選擇。

Next, on our pneumococcal programs. Earlier this month, the FDA extended the PDUFA date for the supplemental biologics license application for VAXNEUVANCE, our 15-valent conjugate pneumococcal vaccine in infants and children to July 1, 2022. The agency requested additional analyses of data, which we provided. Importantly, no new studies were requested.

接下來，關於我們的肺炎球菌計劃。本月早些時候，FDA 將我們的 15 價嬰兒和兒童肺炎球菌疫苗 VAXNEUVANCE 的補充生物製劑許可申請的 PDUFA 日期延長至 2022 年 7 月 1 日。該機構要求對我們提供的數據進行額外分析。重要的是，沒有要求進行新的研究。

Also in our pneumococcal program, we received breakthrough therapy designation for V116, our investigational PCV that is designed to target serotypes responsible for approximately 80% of the residual invasive disease in the older adult population and includes 8 unique serotypes not in currently licensed vaccine. We look forward to providing future updates.

同樣在我們的肺炎球菌項目中，我們獲得了 V116 的突破性治療指定，我們的研究性 PCV 旨在針對導致老年人群中約 80% 殘留侵襲性疾病的血清型，包括目前許可疫苗中沒有的 8 種獨特血清型。我們期待提供未來的更新。

In closing, I would like to thank Roy Baynes for his many contributions to Merck over the past 8 years. As we build upon his legacy, I'm constantly reminded of Roy's business wisdom and teaching, and I'm grateful to work with a remarkable team he has trained and mentored.

最後，我要感謝 Roy Baynes 在過去 8 年中對默克的許多貢獻。隨著我們繼承他的遺產，我不斷地想起 Roy 的商業智慧和教學，我很感激能與他培訓和指導的優秀團隊一起工作。

One of those mentees, of course, is Eliav Barr. Eliav's experience and commitment to Merck's purpose of saving and improving lives makes him the ideal leader of our global clinical development program. Eliav has a wealth of experience, holding leadership roles across an array of therapeutic areas during his 27 years at Merck, including vaccine, infectious disease and oncology. I look forward to continuing to partner with Eliav to build upon Merck's legacy of innovation and breakthrough science.

其中一位學員當然是 Eliav Barr。 Eliav 的經驗和對默克公司拯救和改善生命目標的承諾使他成為我們全球臨床開發計劃的理想領導者。 Eliav 擁有豐富的經驗，在默克公司的 27 年中，他在一系列治療領域擔任領導職務，包括疫苗、傳染病和腫瘤學。我期待繼續與 Eliav 合作，在默克的創新和突破性科學遺產的基礎上再接再厲。

And now back to Peter.

現在回到彼得。

Thank you, Dean. Grace, if you could please begin the Q&A. (Operator Instructions) Thank you.

謝謝你，院長。格蕾絲，如果可以的話，請開始問答。 （操作員說明）謝謝。

(Operator Instructions) Your first question comes from the line of Carter Gould from Barclays.

（操作員說明）您的第一個問題來自 Barclays 的 Carter Gould。

This is [Edward] on for Carter. We wanted to ask about GARDASIL. If you could talk about any impact you're seeing in China, either from a demand perspective or disruptions to manufacturing. And in that context, should we think about cadence -- or should we think about cadence over the year being notably different than in the years past? There's just a lot of different [constants] in play. So any color there would be helpful.

這是卡特的[愛德華]。我們想問一下 GARDASIL。如果你能談談你在中國看到的任何影響，無論是從需求的角度還是對製造業的干擾。在這種情況下，我們應該考慮節奏 - 還是我們應該考慮一年中的節奏與過去幾年顯著不同？有很多不同的[常數]在起作用。所以那裡的任何顏色都會有幫助。

Carter, this is Caroline. Thank you very much for the question. GARDASIL continues to be a great growth driver for our company globally, including China.

卡特，這是卡羅琳。非常感謝您的提問。 GARDASIL 繼續成為我們公司在全球（包括中國）的巨大增長動力。

Specific to China, we saw strong performance in the quarter, and we expect continued strong performance as we go through this year. We have significant demand in China. And as they're [off-play] as a result of COVID and potentially lockdown in one part of the country, we have the ability to ensure that we're supplying more of the GARDASIL doses to other parts of the country. So we're therefore not anticipating a significant impact to our GARDASIL performance in China as a result of what we're seeing in Shanghai at this moment in time.

具體到中國，我們在本季度看到了強勁的表現，我們預計今年將繼續保持強勁的表現。我們在中國有很大的需求。由於 COVID 和該國某個地區的封鎖可能導致它們 [off-play]，我們有能力確保我們向該國其他地區提供更多的 GARDASIL 劑量。因此，由於我們目前在上海看到的情況，我們預計不會對我們在中國的 GARDASIL 業績產生重大影響。

As it pertains to our supply chain, our company has a very robust supply chain. And we have plan A and plan B, if there are any interruptions in the supply chain. So we, again, have no concerns for the reliability of our supply chain, but we remain vigilant and focused on the situation at hand.

由於它與我們的供應鏈有關，我們公司擁有非常強大的供應鏈。如果供應鏈出現任何中斷，我們有 A 計劃和 B 計劃。因此，我們再次不擔心我們供應鏈的可靠性，但我們仍然保持警惕並專注於手頭的情況。

Next up, we have Mohit Bansal from Wells Fargo.

接下來，我們有來自富國銀行的 Mohit Bansal。

Congrats on the quarter. So one question you are getting a lot is how do you feel about potential challenge from a competitor or for PD-L1 and TIGIT combo, potentially looking better than KEYTRUDA in first-line PD-L1-high lung cancer? Do you see this as a major threat, especially looking at the Phase II data from that competitor TIGIT?

祝賀本季度。因此，您經常收到的一個問題是，您如何看待來自競爭對手或 PD-L1 和 TIGIT 組合的潛在挑戰，在一線 PD-L1 高肺癌方面可能看起來比 KEYTRUDA 更好？您是否認為這是一個主要威脅，尤其是從競爭對手 TIGIT 的 II 期數據來看？

Thank you for that question. So I just wanted to emphasize the question focuses on the addition of another checkpoint inhibitor, TIGIT on top of PD-1. And this is a strategy to sort of deepen the response of PD-1 and PD-L1. I think it will be very important to see that data and look at the contribution of components.

謝謝你的問題。所以我只想強調這個問題的重點是在 PD-1 之上添加另一種檢查點抑製劑 TIGIT。這是一種加深 PD-1 和 PD-L1 反應的策略。我認為查看這些數據並查看組件的貢獻將非常重要。

And really, we're -- we have a TIGIT program that we're also advancing in non-small cell lung cancer and small lung cancer. So the field will have to sort of see as the data evolves, how much does TIGIT add to PD-1 in the lung space. But I do want to make a broader sort of comment, which is you'll see movements in TIGIT, there was recently movement in PD-1 and CTLA-4 and PD-1s and LAG-3. What you recognize as each of those combinations, what they do is if you're able to show a benefit of the additional agent, it doesn't have as broad of an impact as PD-1 has in many different tumors.

真的，我們有一個 TIGIT 項目，我們也在推進非小細胞肺癌和小細胞肺癌的研究。因此，隨著數據的發展，該領域將不得不看到 TIGIT 對肺空間中的 PD-1 增加了多少。但我確實想發表更廣泛的評論，你會看到 TIGIT 的變化，最近 PD-1 和 CTLA-4 以及 PD-1s 和 LAG-3 的變化。你認識到這些組合中的每一種，它們所做的是，如果你能夠展示額外藥物的益處，它不會像 PD-1 在許多不同的腫瘤中那樣產生廣泛的影響。

And so one of the things that I think is important to highlight is our strategy is not to just be invested in LAG-3, not to be just invested in CTLA-4, not to be just invested in TIGIT, but to be invested in all 3 and to focus them in specific tumor types.

因此，我認為需要強調的重要一件事是，我們的戰略不僅僅是投資於 LAG-3，不僅僅是投資於 CTLA-4，不僅僅是投資於 TIGIT，而是投資於所有 3 個，並將它們集中在特定的腫瘤類型上。

Next up, we have Seamus Fernandez from Guggenheim.

接下來，我們有來自古根海姆的 Seamus Fernandez。

So just really wanted to focus in on sotatercept and the 6-minute walk test as the primary endpoint. If you guys could just help us understand what is being done in the clinical trial to really manage closely the risk that sort of a subjective endpoint represents? Or is your confidence that the magnitude of the difference that you saw in the Phase II will comfortably cover the challenges of the 6-minute walk test that we've seen in some other studies given some placebo responses that raised levels of concern? So just love to get your thoughts there.

所以只是真的想專注於 sotatercept 和 6 分鐘步行測試作為主要終點。如果你們能幫助我們了解臨床試驗中正在做什麼，以真正密切管理這種主觀終點所代表的風險？或者您是否相信您在第二階段看到的差異幅度將輕鬆涵蓋我們在其他一些研究中看到的 6 分鐘步行測試的挑戰，因為一些安慰劑反應引起了人們的關注？所以只是喜歡把你的想法放在那裡。

Yes. So thank you so much for that question in relationship to sotatercept. So just to reemphasize, we have 3 different trials, all driving towards somewhat different outcomes, the 6-minute walk, which is the STELLAR trial. There's also time to clinical worsening, and then there's also even harder outcomes past that. And as you point out, each one of those is sort of ratcheting up what sotatercept can do.

是的。非常感謝您提出與 sotatercept 相關的問題。因此，再次強調一下，我們有 3 種不同的試驗，所有試驗都朝著不同的結果前進，即 6 分鐘步行，即 STELLAR 試驗。還有時間臨床惡化，然後還有更難的結果。正如你所指出的，每一個都在提高 sotatercept 的功能。

In relationship to the first one, which is STELLAR, which is related to what you said, the 6-minute walk test, where we saw actually quite impressive data and relationship to the Phase II. We have very committed patient groups as well as sites who are very well trained in how to do these trials. And the Phase II was really nice data. And the fundamental issue is that we are confident that many of those same sites that were involved with the Phase II are involved with Phase III. So I think we're confident we'll see what that data is.

關於第一個，即 STELLAR，與您所說的有關，即 6 分鐘步行測試，我們在其中看到了非常令人印象深刻的數據以及與第二階段的關係。我們有非常忠誠的患者群體以及在如何進行這些試驗方面受過良好培訓的站點。第二階段是非常好的數據。最根本的問題是，我們相信參與第二階段的許多相同地點都涉及第三階段。所以我認為我們有信心看到這些數據是什麼。

But the best predictor of how well we can manage those trials is really the best indicator is the Phase II, and we're using there many of the same sites and the investigators. So we have great confidence in them.

但是，我們可以如何管理這些試驗的最佳預測指標實際上是第二階段的最佳指標，我們在那裡使用了許多相同的站點和研究人員。所以我們對他們很有信心。

Next, we have Chris Schott from JPMorgan.

接下來是摩根大通的 Chris Schott。

Maybe just a two-parter around kind of corporate structure. I guess first, business development landscape, I know you talked about this as a priority. I guess it's been another kind of quarter of weak equity market performance in the biotech side. So I guess, are you seeing any change in willingness on the part of some of the targets to engage or any resets in valuations that could enable some of these business development kind of activities to move forward?

也許只是圍繞公司結構的兩部分。我想首先是業務發展前景，我知道您將其作為優先事項進行了討論。我想這是生物技術領域股票市場表現疲軟的又一個季度。所以我想，您是否看到某些目標參與的意願有任何變化，或者估值是否有任何重置，可以使其中一些業務發展類型的活動向前發展？

And then Rob, just a kind of a maybe tangential question on that is broadly across the pharma group, I think we've been seeing asset divestitures of nontraditional pharma businesses. I know you viewed Animal Health as more core to the company. But have your thoughts evolved at all, I guess, as your time as CEO and when you look at your implied kind of core pharma valuation given where some of the animal health multiples trade? So just any incremental perspective there would be appreciated.

然後是 Rob，這只是一個廣泛存在於整個製藥集團的可能切題的問題，我認為我們一直在看到非傳統製藥業務的資產剝離。我知道您將動物保健視為公司的核心。但是，我想，當你擔任 CEO 的時候，以及考慮到一些動物健康倍數的交易時，你的想法是否發生了變化？因此，任何增量的觀點都會受到讚賞。

Great. Chris, thanks for the questions. On the BD landscape question, the short answer is we are not seeing a fundamental shift in seller expectations as of this point. I think as time continues, if we see the market reset to become more permanent and more importantly, if the IPO market continues to be challenged for biotech companies, that might change over time as companies become more cash constrained. There are some smaller players that do have cash challenges. So I think that's where you could see movement first. But fundamentally, we've not seen a change in the landscape yet. We'll have to continue to watch.

偉大的。克里斯，謝謝你的提問。關於 BD 景觀問題，簡短的回答是，到目前為止，我們還沒有看到賣家期望發生根本性轉變。我認為隨著時間的推移，如果我們看到市場重置變得更加持久，更重要的是，如果 IPO 市場繼續受到生物技術公司的挑戰，隨著公司變得更加現金緊張，這種情況可能會隨著時間的推移而改變。有一些較小的玩家確實面臨現金挑戰。所以我認為這是你可以首先看到運動的地方。但從根本上說，我們還沒有看到格局發生變化。我們將不得不繼續觀察。

With regards to the Animal Health business, our view continues to be that the Animal Health business, as you said, is core to the company. It's core to our strategy as part of a growth driver for the company. But as we've always said, we look at this regularly. We always are challenging ourselves to ask what is the long-term value creation opportunity of this business in our hands relative to what would it be outside of the company. And on a long-term view, we continue to believe it is best in our hands as part of the company. But if that situation evolves, we obviously will continue to be objective in how we analyze that. But we do not look at the short term the arbitrage opportunity for us. It's more about the long-term value creation, and that has not changed as of now.

關於動物保健業務，我們的觀點仍然是，正如您所說，動物保健業務是公司的核心。作為公司增長動力的一部分，這是我們戰略的核心。但正如我們一直說的那樣，我們會定期查看這一點。我們一直在挑戰自己，詢問我們手中的這項業務相對於公司外部的長期價值創造機會是什麼。從長遠來看，我們仍然相信作為公司的一部分，它在我們手中是最好的。但如果這種情況發生變化，我們顯然將繼續客觀地分析它。但我們不看短期的套利機會。它更多的是關於長期價值創造，而且到目前為止還沒有改變。

Next up, we have Chris Shibutani from Goldman Sachs.

接下來，我們有來自高盛的 Chris Shibutani。

If I could ask a question on KEYTRUDA, the strength, particularly out of the U.S. this quarter. If you could help us with some of the underpinnings there.

如果我可以問一個關於 KEYTRUDA 的問題，實力，尤其是本季度在美國以外的實力。如果你能幫助我們那裡的一些基礎。

And relatedly, longer term, 2025, I think you framed how KEYTRUDA, your objective is to have -- I guess the wording changed slightly. You were previously looking for 30% coming from adjuvant with your focus framed around the U.S. If I'm reading it correctly, you brought in the framework here to now think about it as 25% on a global basis. Maybe update us on where you feel you are in terms of making progress towards achieving those objectives of the adjuvant revenue contribution.

與此相關的是，從長遠來看，2025 年，我認為您構建了 KEYTRUDA，您的目標是擁有 - 我想措辭略有變化。您之前一直在尋找 30% 來自佐劑，重點圍繞美國。如果我沒看錯的話，您在這裡引入了框架，現在將其視為全球範圍內的 25%。也許在實現輔助收入貢獻的這些目標方面取得進展，讓我們了解您的感受。

Yes. So Chris, this is Rob. Maybe I'll take the first part of the question, then Caroline can jump in for the second part. On the strength of the growth we're seeing in the United States, this is really a testament to what we've been talking about all along, which is as we continue to roll out new indications, we are continuing to see our share grow as the leading I-O agent. And importantly, I would highlight that the growth we saw among other things in the quarter, continuation of our position in renal cell carcinoma, continuation of the growth we're seeing in head and neck. In RCC, obviously, being a first-line treatment in the metastatic setting as well as now having adjuvant therapy as well, we've covered pretty much the waterfront of RCC, and we have the opportunity to continue to grow there.

是的。克里斯，這是羅伯。也許我會回答問題的第一部分，然後 Caroline 可以回答第二部分。鑑於我們在美國看到的增長勢頭，這確實證明了我們一直在談論的內容，即隨著我們繼續推出新的跡象，我們的份額繼續增長作為領先的 I-O 代理。重要的是，我要強調我們在本季度看到的增長，我們在腎細胞癌中的地位的延續，我們在頭頸部看到的增長的延續。顯然，在 RCC 中，作為轉移性環境中的一線治療以及現在也有輔助治療，我們幾乎覆蓋了 RCC 的濱水區，我們有機會繼續在那裡發展。

But the standout frankly, for the quarter, and it's, I think, really important to understand is triple-negative breast cancer, both in the metastatic setting and in the adjuvant setting. We are seeing incredible growth in that space and it's something that we feel very proud of because I think we're going to have a meaningful difference there. The reason I highlight that is both -- if you look at the adjuvant opportunity there and this growth we're getting as well as I mentioned, in adjuvant RCC, I think it just reinforces what we see as the future, which is the growth contribution from the earlier lines of therapy long term. But with that, maybe Caroline can be specific to some of the guidance we've provided.

但坦率地說，對於本季度而言，我認為真正重要的是要了解三陰性乳腺癌，無論是在轉移性環境中還是在輔助性環境中。我們在這個領域看到了令人難以置信的增長，這是我們感到非常自豪的事情，因為我認為我們將在那裡產生有意義的差異。我強調這一點的原因是——如果你看看那裡的輔助機會和我們正在獲得的增長，正如我提到的那樣，在輔助 RCC 中，我認為它只會加強我們所看到的未來，即增長早期治療的長期貢獻。但這樣一來，Caroline 可能會針對我們提供的一些指導進行具體說明。

So to Rob's point, we are extremely excited about the opportunities we have for adjuvant and the impact that, that has on patients. We initially shared that we expected 50% of our growth to come from adjuvant, representing 30% of the U.S. business. We have now extended that to say 50% of the growth will come from adjuvant, representing 25% of our global business in the year 2025.

所以就 Rob 而言，我們對輔助治療的機會及其對患者的影響感到非常興奮。我們最初分享說，我們預計 50% 的增長來自輔助，占美國業務的 30%。我們現在已將其擴展為 50% 的增長將來自輔助，占到 2025 年我們全球業務的 25%。

And to Rob's point, our early introductions into the earlier-stage cancers with 5 indications now in KEYTRUDA are putting us on a very good course to have this impact.

就 Rob 而言，我們現在在 KEYTRUDA 中對具有 5 種適應症的早期癌症進行了早期介紹，這使我們走上了產生這種影響的非常好的道路。

Next, we have Umer Raffat from Evercore ISI.

接下來是來自 Evercore ISI 的 Umer Raffat。

Maybe let me touch up on molnupiravir real quick. I think the total utilization to date is about 200,000 courses through mid-April. And it looks like, at least based on third-party data sets, that the Pfizer regimen is getting used 8 to 10x more than molnupiravir. So I guess my question is, if only a couple hundred thousand courses have been used through mid-April and 3.1 million courses were contracted to U.S., is there any recourse for U.S. to return a chunk of these courses back? And I'm asking because some of these sales have been recorded in P&L. I just want to make sure they're permanent sales.

也許讓我快速了解一下莫努匹拉韋。我認為截至 4 月中旬，迄今為止的總利用率約為 200,000 門課程。而且看起來，至少基於第三方數據集，輝瑞療法的使用率是莫努匹韋的 8 到 10 倍。所以我想我的問題是，如果到 4 月中旬只使用了幾十萬門課程，並且與美國簽約了 310 萬門課程，那麼美國是否有任何追索權將這些課程中的一部分退回？我之所以問，是因為其中一些銷售額已記錄在損益表中。我只是想確保它們是永久銷售。

Yes. I'll let Caroline maybe address this.

是的。我會讓 Caroline 解決這個問題。

So Umer, thanks for the question. First, let me start. We're proud of molnupiravir, LAGEVRIO and the impact that it can have on the world. And it has impact to the comments that Dean made given its importance, especially in patients that have drug-to-drug interactions.

所以，Umer，謝謝你的問題。首先，讓我開始吧。我們為 molnupiravir、LAGEVRIO 及其對世界的影響感到自豪。鑑於其重要性，它對 Dean 發表的評論產生了影響，尤其是在具有藥物間相互作用的患者中。

The data that we have access to suggest that we have actually had utilization by 500,000 patients globally at this stage. We have shipped 6.4 million courses as of now. Both shipments represent expectations for utilization over a period of time. And we're actually seeing extremely strong utilization, especially in ex U.S. markets, where the statistics you quote are actually reversed in some of the markets. We have a very strong market share. So as we sit here today, we've guided on the $5 billion to $5.5 billion based on the contracts that we have in hand, and we are confident in that in our financials.

我們可以訪問的數據表明，在這個階段，我們實際上已經被全球 500,000 名患者使用。截至目前，我們已經運送了 640 萬門課程。兩批貨物都代表了一段時間內的利用率預期。我們實際上看到了非常強勁的利用率，特別是在美國以外的市場，您引用的統計數據在某些市場實際上是相反的。我們擁有非常強大的市場份額。因此，當我們今天坐在這裡時，我們已經根據我們手頭的合同指導了 50 億至 55 億美元，我們對我們的財務狀況充滿信心。

Next, we have Daina Graybosch from SVB Leerink.

接下來，我們有來自 SVB Leerink 的 Daina Graybosch。

I have another one on KEYTRUDA in early stage. Can you please talk to how the success of Opdivo plus chemotherapy in neoadjuvant lung cancer changes your expectations or strategy for the early-stage opportunities in lung cancer and then in the other tumor?

早期我在 KEYTRUDA 上還有一個。您能否談談 Opdivo 聯合化療在新輔助肺癌中的成功如何改變您對肺癌早期機會以及其他腫瘤的預期或策略？

Yes. Thank you very much for that question. In relationship to sort of just earlier stage in lung cancer, I think it's really important to emphasize, there's a series of different ways to approach it. One is neoadjuvant adjuvant. One is adjuvant. And I just think all of these signals just demonstrate throughout a variety of different studies just the impact that PD-1s can have.

是的。非常感謝你提出這個問題。關於肺癌的早期階段，我認為強調這一點非常重要，有一系列不同的方法來處理它。一種是新輔助佐劑。一是佐劑。我只是認為所有這些信號只是通過各種不同的研究證明了 PD-1 可以產生的影響。

So our point of view of it is it shouldn't change our strategy, it should just make our strategy pretty comprehensive. The fundamental thing is we have KEYNOTE-091, which is in the adjuvant, so that's post-surgery, and that's usually given by a medical oncologist. The disease-free survival was positive in all-comers regardless of PD-L1. There was a trend to TPS greater than 50%, but not statistically significant. And OS, it was a favorable trend regardless of PD-L1. So we'll be letting that data mature as we continue to discuss with the FDA.

所以我們的觀點是它不應該改變我們的策略，它應該只是讓我們的策略相當全面。最重要的是我們有 KEYNOTE-091，它在佐劑中，所以這是在手術後，通常由腫瘤內科醫生提供。無論PD-L1如何，所有患者的無病生存都是陽性的。 TPS 有大於 50% 的趨勢，但沒有統計學意義。而OS，無論PD-L1如何，都是一個有利的趨勢。因此，隨著我們繼續與 FDA 討論，我們將讓這些數據成熟。

But going to your point, it's not just KEYNOTE-091. It's KEYNOTE-671, it's KEYNOTE-867, it's KEYLYNK-012. It's all in the earlier stage. So our desire to really push that earlier stage is going to be, if anything, our commitment towards that is even greater.

但說到你的意思，它不僅僅是 KEYNOTE-091。它是 KEYNOTE-671，它是 KEYNOTE-867，它是 KEYLYNK-012。這一切都在早期階段。因此，我們真正推動更早階段的願望將是，如果有的話，我們對此的承諾會更大。

The one thing I would just add in relationship to some of the comments that Caroline and Rob made is that I think it's very important to think about melanoma renal cell carcinoma and triple-negative breast cancer, where at least my experience being in the hospital, there's a concept of really looking at that earlier stage. And I think uptake may be sort of built in the medical system.

關於卡羅琳和羅布的一些評論，我要補充的一件事是，我認為考慮黑色素瘤腎細胞癌和三陰性乳腺癌非常重要，至少我在醫院的經歷，有一個真正關注早期階段的概念。而且我認為吸收可能是在醫療系統中建立的。

I think all of us, including us and other companies as well as patient advocacies and medical centers are going to have to require diligent investment to really, really maximize the important scientific impacts of KEYTRUDA and PD-1s and PD-L1s in the early lung space.

我認為我們所有人，包括我們和其他公司以及患者倡導和醫療中心都將不得不進行勤奮的投資，以真正、真正最大限度地發揮 KEYTRUDA 和 PD-1s 和 PD-L1s 在早期肺部的重要科學影響空間。

Next, we have Andrew Baum from Citi.

接下來，我們有來自花旗的 Andrew Baum。

I'd just like to thank Roy for all the contributions and insights over the years. The question is on your Factor XI monoclonal. Given your background in cardiology, and I'm sure you keep familiarity with hemostasis team. There's clearly been a number of indications where the DOACs were unsuccessful compared to warfarin for both efficacy and safety, potentially speaking to different underlying mechanisms for thrombosis and a different indication as I'm thinking about [ESS], I'm thinking about mechanical heart valves. Given what you know about Factor XI biology and the intrinsic pathway nature of the inhibition, what indications would you actively avoid or be somewhat cautious about taking a Factor XI inhibitor into, be it yours or someone else's?

我只想感謝 Roy 多年來的所有貢獻和見解。問題在於您的因子 XI 單克隆抗體。鑑於您在心髒病學方面的背景，我相信您對止血團隊很熟悉。與華法林相比，顯然有許多跡象表明 DOAC 在療效和安全性方面均不成功，這可能與血栓形成的不同潛在機制和不同的適應症有關，因為我正在考慮 [ESS]，我正在考慮機械心臟閥門。鑑於您對因子 XI 生物學和抑制的內在途徑性質的了解，您會積極避免或謹慎使用因子 XI 抑製劑，無論是您的還是其他人的？

Yes. So let me just step back for just a moment. The benefit risk of whether it's platelet or coagulation factors in terms of clotting is something that's actually very topical in the news. I would just emphasize for years, for probably a decade or more, aspirin has been just everywhere. And recently, people realize the benefit risk, one has to be very careful. There has been a major change in the guideline. So that impacts how I think about it.

是的。所以讓我退後一會兒。無論是血小板還是凝血因子在凝血方面的益處風險實際上是新聞中非常熱門的話題。我只想強調多年來，可能十年或更長時間，阿司匹林無處不在。而最近，人們意識到利益風險，必須非常小心。指導方針發生了重大變化。所以這會影響我對它的看法。

The other sort of thing that impact is, if you look at Factor XI, the fundamental advantage of that is that you can get blockage of the coagulation cascade with, by genetic, very little impact in relationship to adverse effect. And so for me, the critical thing is to prove that as quickly as possible. So we immediately go where is the problem, where thrombosis and bleeding is both impacted there. And so that's why we ran the end-stage renal disease.

另一種影響是，如果您查看因子 XI，其基本優勢是您可以通過遺傳阻斷凝血級聯反應，而與不利影響相關的影響非常小。所以對我來說，關鍵是盡快證明這一點。因此，我們立即找到問題所在，血栓形成和出血都受到影響的地方。這就是我們進行終末期腎病的原因。

But I could see in the future mechanical devices, one of my favorite sort of things is left ventricular assist device. I think that will continue to need to be monitored in the future. So that's a place where the risk of bleeding and the risk of thrombosis is really high.

但我可以看到在未來的機械設備中，我最喜歡的一類東西是左心室輔助設備。我認為這將在未來繼續需要監測。所以這是一個出血風險和血栓形成風險非常高的地方。

Where we have chosen to be a little bit careful is, for example, broader sort of things such as atrial fibrillation and the risk relationship to stroke because we look at the Factor X as very effective. There are bleeding complications, but to make a safety argument for it, you're talking about a very, very large trial. So we are racing to places where the benefit risk of thrombosis and clotting and bleeding, where that differential would make something like a Factor XI have the biggest impact.

例如，我們選擇稍微小心的地方是更廣泛的事情，例如心房顫動和與中風的風險關係，因為我們認為 X 因素非常有效。有出血並發症，但要為它做一個安全的論據，你說的是一個非常非常大的試驗。因此，我們正在努力爭取血栓形成、凝血和出血的獲益風險，在那裡，這種差異將使因子 XI 之類的東西產生最大的影響。

Next, we have Louise Chen from Cantor.

接下來，我們有來自 Cantor 的 Louise Chen。

I wanted to ask you about your pneumococcal conjugate vaccine. And how you think your more targeted approach will be a competitive advantage versus the one-size-fits-all that we're seeing now? And is there any precedence to what you're doing with V116 and 117? And maybe just lastly, how will you make that message clear to physicians since if everything goes as planned, you'll have several PCVs on the market?

我想問你關於肺炎球菌結合疫苗的問題。與我們現在看到的千篇一律的方法相比，您認為更具針對性的方法將如何成為競爭優勢？你用 V116 和 117 做的事情有什麼優先級嗎？也許最後一點，如果一切按計劃進行，您將如何向醫生傳達這一信息，那麼您將在市場上擁有幾台 PCV？

Yes. First of all, we need to get the data to demonstrate that we have an advantage in the different patient populations. But I think you point out a really important point, which is essentially what we're trying to do is, for lack of a better word, we're -- if you want to call it, precision-targeted vaccinations, right? So the fundamental thing is V114 is adult approved and we're driving towards a pediatric approval for the 15-valent. And so that will be in the pediatric population.

是的。首先，我們需要獲取數據來證明我們在不同的患者群體中具有優勢。但我認為你指出了一個非常重要的點，這基本上就是我們正在嘗試做的，因為沒有更好的詞，我們是——如果你想稱之為精確靶向疫苗，對吧？所以基本的事情是 V114 是成人批准的，我們正在推動 15 價的兒科批准。所以這將是在兒科人群中。

In the V116, where we have a breakthrough designation, we're trying to demonstrate that we can target 85% of the residual serotypes. And I would just sit there and tell you it would be 8 unique serotypes in relationship to all the different currently approved ones. And I think that patient population, I reflect a little bit about COVID, but it's that older population that especially has the risk factors who you really want to make sure that, that whole population, that adult population is covered.

在 V116 中，我們有一個突破性的名稱，我們試圖證明我們可以針對 85% 的殘留血清型。我會坐在那裡告訴你，這將是 8 種獨特的血清型，與目前批准的所有不同的血清型有關。我認為患者群體，我對 COVID 有所反映，但老年人群體尤其具有風險因素，你真正想確保覆蓋整個人群和成年人群。

And so I do think the fundamental thing is we'll have to have the data, but our concept is the adult have a different set of serotypes and they need to be protected, and we'll have to get the data to demonstrate that. But I think if we can demonstrate it, the uptake will be quite good.

所以我確實認為最基本的事情是我們必須擁有數據，但我們的概念是成年人有一組不同的血清型，它們需要受到保護，我們必須獲得數據來證明這一點。但我認為，如果我們能夠證明這一點，那麼吸收會非常好。

Next, we have Mara Goldstein from Mizuho.

接下來，我們有來自瑞穗的 Mara Goldstein。

I'm just hoping maybe we can return for a second back to the question of novel targets in combination with KEYTRUDA. And maybe if you could just give us a very high level, perhaps rationale, for which targets you're looking at and which indications. And I'm referring here, obviously, two things like TIGIT, LAG-3, ILT3 and the like.

我只是希望也許我們可以回到與 KEYTRUDA 結合的新目標問題上。也許你能給我們一個非常高的水平，也許是理由，你正在關注哪些目標和哪些跡象。顯然，我在這裡指的是 TIGIT、LAG-3、ILT3 等兩件事。

All right. So let me just sort of separate. So we always talk about expand, deepen and extend. And when we talk about deepen, we're trying to get a deeper response with PD-1s. And there's a series of things that we do with what I call non-I-O agents, which is chemotherapy. We're doing stuff with many other people as well as ourselves with ADCs. Our RAS programs are advancing. So we think that, that sort of combination, there's large precedent throughout our portfolio already, and there will continue to be. And that's also true with Lenvima and Lynparza.

好的。所以讓我有點分開。所以我們總是談論擴大、深化和延伸。當我們談論加深時，我們正試圖通過 PD-1 獲得更深層次的回應。我們用我所說的非 I-O 代理做一系列的事情，也就是化療。我們正在與許多其他人以及我們自己與 ADC 一起做事。我們的 RAS 計劃正在推進。所以我們認為，這種組合在我們的投資組合中已經有了很多先例，而且還會繼續存在。 Lenvima 和 Lynparza 也是如此。

The specific question I think you're driving to is combinations of I-O with I-O agents and LAG-3, CTLA-4 and TIGIT. So at least in our mind, we do recognize that there was demonstration of LAG-3 adding to PD-1 in melanoma. And I think that's an important signal for us. Where we focused our effort to LAG-3 is in MSS CRC. So we know that PD-1s work in MSI-high, and no one's really been able to crack MSS CRC. So that's very important and also in classic Hodgkin's. I would say, in relationship with CTLA-4, there was recent data with HCC.

我認為您要解決的具體問題是 I-O 與 I-O 代理以及 LAG-3、CTLA-4 和 TIGIT 的組合。所以至少在我們看來，我們確實認識到在黑色素瘤中存在 LAG-3 添加到 PD-1 的證據。我認為這對我們來說是一個重要的信號。我們將精力集中在 LAG-3 上的是 MSS CRC。所以我們知道 PD-1 在 MSI-high 下工作，沒有人真正能夠破解 MSS CRC。所以這非常重要，在經典的霍奇金小說中也是如此。我想說，就 CTLA-4 而言，最近有關於 HCC 的數據。

I would make a comment that I think would make some of the people from Merck smile a little bit. We were the ones who actually did the study with PD-1 and CTLA-4 in relationship to lung. And we could not show a clear contribution of component of CTLA-4 over PD-1. So that is not a place that we think is an important place for patients, and that is not a place that we're going because we have -- we did the study to demonstrate that. Where we think there could be is, clearly, other people have recently released HCC. We're focused in, for example, in renal cell carcinoma. And then PD-1 and TIGIT, our initial focus is non-small cell lung cancer and also small cell lung cancer. And we're advancing a series of trials in that.

我會發表評論，我認為這會讓默克的一些人微笑。我們是實際使用 PD-1 和 CTLA-4 與肺相關的研究的人。而且我們無法顯示 CTLA-4 的成分對 PD-1 的明顯貢獻。所以這不是我們認為對患者來說重要的地方，也不是我們要去的地方，因為我們有——我們做了研究來證明這一點。顯然，我們認為可能有其他人最近發布了 HCC。例如，我們專注於腎細胞癌。然後是 PD-1 和 TIGIT，我們最初的重點是非小細胞肺癌和小細胞肺癌。我們正在推進一系列的試驗。

So I hope that gave a comprehensive view of LAG-3, CTLA-4 and TIGIT. In relationship to ILT4, other checkpoint inhibitors such as CD27 or in relationship to cytokines, I think the data that we're doing in earlier stages will have to play out for us to be able to answer that more completely.

所以我希望對 LAG-3、CTLA-4 和 TIGIT 有一個全面的了解。關於 ILT4、CD27 等其他檢查點抑製劑或與細胞因子的關係，我認為我們在早期階段所做的數據必鬚髮揮作用，我們才能更完整地回答這個問題。

Great. Thank you, Mara. I think we have time for one more question, and Rob will have a few closing comments.

偉大的。謝謝你，瑪拉。我想我們還有時間再提一個問題，Rob 將發表一些結束語。

Last question comes from the line of Colin Bristow from UBS.

最後一個問題來自瑞銀的 Colin Bristow。

Congrats on the quarter. And I also wanted to say all the best to Roy. It's been really great working with you, and also congrats to Eliav. So I just wanted to piggyback on a GARDASIL question. Could you maybe just give us a little more detail on how you expect the GARDASIL supply to increase? And then maybe just help us think through what is the supply/demand mismatch right now? Some of your prior comments suggested that there may not be such. But I know you said supply has been an issue over the past sort of couple of years. So would love to get some expanded thoughts there.

祝賀本季度。我也想對羅伊說一切順利。和你一起工作真的很棒，也祝賀 Eliav。所以我只是想附帶一個 GARDASIL 問題。您能否更詳細地說明您預計 GARDASIL 供應量將如何增加？然後也許只是幫助我們思考一下現在的供需不匹配是什麼？您之前的一些評論表明可能沒有這樣的情況。但我知道你說過供應在過去幾年一直是個問題。所以很想在那裡得到一些擴展的想法。

Thank you for the question. This is Caroline. So let me start first with the supply/demand. There is significant demand for GARDASIL. This cancer-preventing vaccine in the HPV area has only reached today 9% of the global eligible population. So there is significant runway ahead of us to protect lives and to drive growth for Merck. Indeed, we've stated that we expect the revenue in year 2030 to be double the $5.7 billion we achieved in 2021. So we have significant opportunity ahead of us.

感謝你的提問。這是卡羅琳。因此，讓我首先從供需開始。對 GARDASIL 的需求很大。 HPV 領域的這種預防癌症的疫苗如今僅覆蓋全球 9% 的合格人群。因此，在保護生命和推動默克公司的增長方面，我們前面還有很長的路要走。事實上，我們已經表示，我們預計 2030 年的收入將是我們在 2021 年實現的 57 億美元的兩倍。因此，我們面臨著巨大的機遇。

In order to achieve that opportunity, we are building new facilities that will be coming online from 2023, 2024 and 2025. So we're going to have a step-up in the level of supply to the market that will happen over that period.

為了抓住這個機會，我們正在建設新設施，這些設施將於 2023 年、2024 年和 2025 年投入使用。因此，我們將在此期間提高市場供應水平。

Specific then to this year, we will see a continuation of the supply into the market as we did in 2021, albeit not quite at the same step-up that we achieved in 2021. So we remain really confident in our ability to drive strong growth for GARDASIL both in 2022 and the years to come.

具體到今年，我們將看到市場供應繼續像我們在 2021 年所做的那樣，儘管與我們在 2021 年實現的增幅不同。因此，我們對推動強勁增長的能力仍然充滿信心GARDASIL 在 2022 年和未來幾年。

Great. Thank you, Colin. Rob?

偉大的。謝謝你，科林。搶？

Well, just let me say thank you for your time and your interest today. And I'd just like to conclude by again thanking the Merck team globally for their focus and commitment and really in driving the results you've heard about today, but in continuing to ensure we keep the purpose of the company front and center, which is to deliver for patients.

好吧，讓我對您今天的時間和興趣表示感謝。最後，我想再次感謝默克全球團隊的專注和承諾，真正推動了你們今天聽到的結果，但繼續確保我們保持公司的首要目標，即是給病人送的。

Hopefully, you get the sense, we are very confident in the business momentum we have. And I'd like to say as well, we are feeling better and better about the evolution of our pipeline and what you've heard today, we're starting to expand. We're doing all of the things we need to do. We have more to do, but we're making great progress. And that's why I have such confidence in the sustainability of our business long term. So we look forward to continuing to share these results with you to deliver for the patients that count on us and in turn, bring value to the shareholders.

希望您能明白，我們對我們擁有的業務發展勢頭非常有信心。我還想說，我們對管道的發展感覺越來越好，你們今天聽到的，我們開始擴大。我們正在做我們需要做的所有事情。我們還有更多工作要做，但我們正在取得很大進展。這就是為什麼我對我們業務的長期可持續性充滿信心。因此，我們期待繼續與您分享這些結果，為依賴我們的患者提供服務，進而為股東帶來價值。

So with that, I'd say thank you and have a great day.

因此，我想說謝謝你，祝你有美好的一天。

Thank you so much, presenters. This concludes today's conference call. Thank you all for joining. You may now all disconnect.

非常感謝各位主持人。今天的電話會議到此結束。謝謝大家的加入。您現在可以全部斷開連接。