默克藥廠 (MRK) 2023 Q3 法說會逐字稿

Welcome to the Merck & Company Q3 Sales and Earnings Conference Call.

歡迎參加默克公司第三季銷售和獲利電話會議。

(Operator Instructions)

（操作員說明）

This call is being recorded.

此通話正在錄音。

(Operator Instructions)

（操作員說明）

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

我現在會把電話轉給投資者關係副總裁 Peter Dannenbaum 先生。先生，您可以開始了。

Thank you, Julie, and good morning, everyone. Welcome to Merck's Third Quarter 2023 Conference Call. .

謝謝朱莉，大家早安。歡迎參加默克 2023 年第三季電話會議。 。

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.

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。您將看到我們的 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.

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。此類陳述是基於當前的信念而做出的。默克管理層的責任，並面臨重大風險和不確定性。

If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Our SEC filings, including Item 1A in the 2022 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.

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。我們向SEC 提交的文件（包括2022 年10-K 中的第1A 項）確定了某些風險因素和警示性聲明，這些因素可能導致公司的實際結果與我們今天上午做出的任何前瞻性聲明中的預測存在重大差異。

Merck undertakes no obligation to publicly update any forward-looking statements. During today's call, slide presentation will accompany our speakers' prepared remarks. These slides, along with the earnings release, today's prepared remarks and our SEC filings are all posted to the Investor Relations section of Merck's website.

默克不承擔公開更新任何前瞻性聲明的義務。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。這些投影片以及收益發布、今天準備的評論和我們向 SEC 提交的文件均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 continue to bring forward innovation that can save and improve the lives of patients and animals around the world. We're advancing our broad pipeline and executing in support of our key growth drivers, enabling strong progress for our business and providing tangible benefits to patients. To that end, I want to acknowledge the efforts of our talented global team. Their passion and commitment to our science-led strategy are fundamental to our continued success.

謝謝，彼得。早安，感謝您參加今天的電話會議。我們不斷推動創新，拯救和改善世界各地患者和動物的生活。我們正在推動廣泛的產品線和執行工作，以支持我們的關鍵成長動力，使我們的業務取得強勁進展，並為患者提供切實的好處。為此，我要感謝我們才華橫溢的全球團隊所做的努力。他們對我們以科學為主導的策略的熱情和承諾是我們持續成功的基礎。

Scientific innovation is truly the foundation of our strategy, and it drives everything we do. We're pushing the boundaries of science through the significant investments we are making across our deep pipeline, augmented by strategic business development. I'm pleased by the continued progress with these programs and our growing diversity across new therapeutic areas and modalities.

科學創新確實是我們策略的基礎，它驅動著我們所做的一切。我們透過在深層管道上進行的重大投資，並透過策略性業務發展來擴大科學的界限。我對這些計畫的持續進展以及我們在新的治療領域和模式上不斷增長的多樣性感到高興。

Along these lines, we're particularly excited by our recently announced clinical and commercial collaboration with Daiichi Sankyo for 3 potentially first-in-class antibody drug conjugates. The scientists at Daiichi Sankyo are proven innovators in this space, having developed proprietary ADC technology that has resulted in an approved product, which is being rapidly adopted for patients with certain cancers. We're privileged to begin working alongside them to advance this important science and achieve both companies' objectives of addressing the significant unmet patient need in oncology.

沿著這些思路，我們對最近宣布與第一三共就 3 種潛在的一流抗體藥物綴合物進行臨床和商業合作感到特別興奮。第一三共的科學家們是該領域久經考驗的創新者，他們開發了專有的 ADC 技術，並生產了經過批准的產品，該產品正在迅速應用於某些癌症患者。我們很榮幸能夠開始與他們合作，推動這項重要的科學發展，並實現兩家公司的目標，即解決腫瘤學領域未滿足的重大患者需求。

Based on our strong conviction in these programs and the profound benefit they may bring to patients, we believe each has multibillion-dollar commercial revenue potential for Merck on a non-risk-adjusted basis approaching the mid-2030s. We're also applying our clinical expertise to accelerate the development of other potentially transformative treatments that we've added through strategic business development, such as Sotatercept for pulmonary arterial hypertension and MK-7240 our TL1A inhibitor for ulcerative colitis and Crohn's disease. This is complemented by our strong commercial execution capabilities, which we expect to amplify the impact of these life-changing medicines and enable the creation of sustainable value for patients and shareholders over the long term.

基於我們對這些項目的堅定信念以及它們可能為患者帶來的深遠利益，我們相信到2030 年代中期，在非風險調整的基礎上，每個項目都將為默克帶來數十億美元的商業收入潛力。我們也運用我們的臨床專業知識來加速開發透過策略性業務發展添加的其他潛在變革性治療藥物，例如用於治療肺動脈高壓的Sotatercept 和用於治療潰瘍性結腸炎和克羅恩病的TL1A 抑制劑MK -7240。我們強大的商業執行能力對此予以補充，我們希望擴大這些改變生活的藥物的影響，並為患者和股東創造長期的永續價值。

Turning to this quarter's performance. We delivered robust growth driven by demand for our innovative portfolio. We're confident that we will close out 2023 with continued strong performance, which is reflected in the updated full year outlook that Caroline will speak to in a few minutes.

轉向本季的業績。在對我們創新產品組合的需求的推動下，我們實現了強勁的成長。我們有信心以持續強勁的業績結束 2023 年，卡羅琳將在幾分鐘後發表的最新全年展望中反映了這一點。

Moving to our research organization. As I mentioned, we're making remarkable progress across multiple therapeutic areas and our promising late-phase pipeline. In oncology, Dean will speak to the significant success we're having in broadly leveraging the foundational position that we've achieved with KEYTRUDA. This includes the continued advancements we're making in the treatment of early-stage cancers.

轉向我們的研究組織。正如我所提到的，我們在多個治療領域和我們有前途的後期管道方面取得了顯著進展。在腫瘤學方面，Dean 將談到我們在廣泛利用 KEYTRUDA 所取得的基礎地位方面所取得的重大成功。這包括我們在早期癌症治療方面不斷取得的進展。

We're very excited by the recent FDA approval of a KEYTRUDA regimen for the neoadjuvant and adjuvant treatment of certain patients with resectable non-small cell lung cancer based on the KEYNOTE-671 trial results, which notably demonstrated an improvement in overall survival compared to a placebo and chemotherapy regimen.

我們非常高興 FDA 最近根據 KEYNOTE-671 試驗結果批准了 KEYTRUDA 方案，用於對某些可切除非小細胞肺癌患者進行新輔助和輔助治療，該試驗顯著證明了與安慰劑和化療方案。

In addition, we presented numerous important data sets at last week's European Society for Medical Oncology Meeting across a wide range of molecules, tumor types and indications. Our progress across a broad set of programs reinforces our confidence in the sustainability of our oncology leadership well into the next decade.

此外，我們在上週的歐洲腫瘤內科學會會議上展示了大量涉及廣泛分子、腫瘤類型和適應症的重要數據集。我們在一系列廣泛計劃中取得的進展增強了我們對未來十年腫瘤學領導地位可持續性的信心。

We're also making exciting progress in our cardiometabolic pipeline. Most significantly, the FDA accepted for proprietary review our filing for Sotatercept based on the unprecedented results of the STELLAR trial, and we look forward to the potential approval and launch in early 2024. We remain confident that Sotatercept has the potential to change the treatment paradigm for patients suffering with pulmonary arterial hypertension.

我們在心臟代謝管道方面也取得了令人興奮的進展。最重要的是，FDA 基於 STELLAR 試驗的前所未有的結果接受了我們對 Sotatercept 的專利審查，我們期待在 2024 年初獲得批准並上市。我們仍然相信 Sotatercept 有潛力改變治療模式對於患有肺動脈高壓的患者。

We also initiated Phase III clinical trials for our oral PCSK9 candidate, MK-0616. We believe MK-0616 has the potential to provide significant benefit to patients with elevated cholesterol and impact cardiovascular disease on a global scale. We're very pleased with our progress and what we've achieved this quarter as we continue to focus on advancing and expanding Merck's pipeline, and I want to thank Dean and his team for their unwavering commitment to addressing unmet patient needs.

我們也啟動了口服 PCSK9 候選藥物 MK-0616 的 III 期臨床試驗。我們相信 MK-0616 有潛力為膽固醇升高的患者帶來顯著的益處，並在全球範圍內影響心血管疾病。我們對本季的進展和所取得的成就感到非常滿意，因為我們繼續專注於推進和擴大默克的產品線，我要感謝 Dean 和他的團隊對解決未滿足的患者需求的堅定承諾。

In summary, we continue to move with urgency to deliver on our purpose, pursuing transformative science to save and improve lives around the world. We're executing scientifically, commercially and operationally on the significant opportunities now in front of us, while also making the disciplined investments needed to sustain strong growth well into the future. With the efforts of our global team, we've increased confidence that we will deliver value to patients, shareholders and to all of our stakeholders. With that, I'll turn the call over to Caroline.

總之，我們繼續迫切地實現我們的目標，追求變革性科學來拯救和改善世界各地的生活。我們正在以科學、商業和營運的方式抓住眼前的重大機遇，同時進行嚴格的投資，以維持未來的強勁成長。在我們全球團隊的努力下，我們更有信心為病人、股東和所有利害關係人創造價值。這樣，我就把電話轉給卡洛琳。

Thank you, Rob. Good morning. As Rob highlighted, we achieved very strong growth this quarter, driven by robust underlying demand across our innovative portfolio, and we remain confident in our ability to continue to deliver strong results in the near term. We are also making disciplined investments to leverage leading-edge science to save and improve lives around the world well into the future, positioning us to deliver long-term value for patients and shareholders.

謝謝你，羅布。早安.正如 Rob 所強調的那樣，在我們創新產品組合強勁的潛在需求的推動下，我們本季度實現了非常強勁的增長，並且我們對在短期內繼續取得強勁業績的能力仍然充滿信心。我們也進行嚴格的投資，利用前沿科學來拯救和改善世界各地的未來生活，使我們能夠為患者和股東帶來長期價值。

Now turning to our third quarter results. Total company revenues were $16 billion. Excluding the impact from LAGEVRIO and foreign exchange, the business delivered strong growth of 8%. The remainder of my revenue comments will be on an ex-exchange basis.

現在轉向我們的第三季業績。公司總收入為 160 億美元。剔除LAGEVRIO和外匯的影響，該業務實現了8%的強勁成長。我其餘的收入評論將基於交換基礎上。

Our Human Health business sustained its strong momentum. Excluding LAGEVRIO, growth was 10%, driven by oncology and vaccines. Sales in our Animal Health business increased 2%.

我們的人類健康業務保持強勁勢頭。不包括 LAGEVRIO，在腫瘤學和疫苗的推動下，增加了 10%。我們的動物保健業務銷售額成長了 2%。

Turning to the performance of our key brands. In oncology, sales of KEYTRUDA grew 17% to $6.3 billion, driven by increased uptake from earlier-stage cancers and continued strong global demand for metastatic indications. In the U.S., KEYTRUDA growth was driven by increased utilization in both metastatic indications and earlier stage cancers, such as triple-negative breast cancer.

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增加以及全球對轉移適應症的持續強勁需求，KEYTRUDA 的銷售額增長了 17%，達到 63 億美元。在美國，KEYTRUDA 的成長是由轉移適應症和早期癌症（例如三陰性乳癌）的利用率增加所推動的。

Uptake in earlier stages of non-small cell lung cancer remains strong, and KEYTRUDA has now achieved brand leadership in this setting, reflecting the significant impact it is having as adjuvant treatment for patients with Stage Ib to IIIa disease.

非小細胞肺癌早期階段的使用仍然強勁，KEYTRUDA 現已在這一領域取得了品牌領導地位，反映出它作為 Ib 至 IIIa 期疾病患者的輔助治療所產生的重大影響。

Our recently approved KEYNOTE-671 indication provides an important additional treatment options to patients and physicians by including usage in the neoadjuvant and adjuvant setting. We remain exceptionally well positioned to serve patients with non-small cell lung cancer and extend our leadership to the earlier-stage setting.

我們最近批准的 KEYNOTE-671 適應症透過在新輔助和輔助治療中使用，為患者和醫生提供了重要的額外治療選擇。我們仍然處於非常有利的地位，可以為非小細胞肺癌患者提供服務，並將我們的領導地位擴展到早期階段。

In bladder cancer, we are excited to potentially expand usage of KEYTRUDA to Cisplatin-eligible patients based on the compelling results from the KEYNOTE-A39 study. If approved, this study would more than double the eligible patient population for KEYTRUDA in first-line bladder cancer.

在膀胱癌方面，基於 KEYNOTE-A39 研究令人信服的結果，我們很高興能夠將 KEYTRUDA 的使用範圍擴大到符合順鉑資格的患者。如果獲得批准，這項研究將使符合 KEYTRUDA 一線膀胱癌治療資格的患者人數增加一倍以上。

Outside the U.S., KEYTRUDA growth was driven by uptake in earlier stage cancers, including high-risk early-stage triple-negative breast cancer and renal cell carcinoma as well as increased demand in metastatic renal cell carcinoma and certain types of head and neck cancer. Lynparza remains the market-leading PARP inhibitor, with alliance revenue growing 6% this quarter. Lenvima alliance revenue had growth of 30%, driven by shipment timings in China, which we expect will negatively impact growth in the fourth quarter. Growth was also driven by increased demand for the treatment of certain patients with advanced renal cell carcinoma and endometrial cancer in the U.S.

在美國以外，KEYTRUDA 的成長是由早期癌症的吸收所推動的，包括高風險的早期三陰性乳癌和腎細胞癌，以及轉移性腎細胞癌和某些類型的頭頸癌的需求增加。 Lynparza 仍然是市場領先的 PARP 抑制劑，本季聯盟營收成長 6%。受中國出貨時間的推動，Lenvima 聯盟營收成長了 30%，我們預計這將對第四季的成長產生負面影響。美國某些晚期腎細胞癌和子宮內膜癌患者的治療需求增加也推動了成長。

Our vaccines portfolio delivered strong growth, led by GARDASIL, which increased 16% to $2.6 billion, driven by underlying global demand, particularly in China. In the U.S., GARDASIL sales decreased due to CDC purchasing patterns. Vaccine sales also benefited from continued uptake in the pediatric indication of VAXNEUVANCE in the U.S. and its launch in key European markets.

我們的疫苗產品組合在 GARDASIL 的帶動下實現了強勁增長，在全球潛在需求（尤其是中國）的推動下，增長了 16%，達到 26 億美元。在美國，由於 CDC 的採購模式，GARDASIL 的銷售量有所下降。疫苗銷售也受益於 VAXNEUVANCE 兒科適應症在美國的持續接受度以及其在歐洲主要市場的推出。

In our Hospital Acute Care portfolio, BRIDION sales were flat as increased market share among neuromuscular blockade reversal agents in the U.S. was offset by the impact of generic entry in Europe. Sales in our Animal Health business grew 2%. Livestock sales grew 7%, reflecting price actions as well as higher demand for ruminant products. Companion animal sales declined due to a reduction in vet visits in the U.S., partially offset by pricing actions.

在我們的醫院急性護理產品組合中，BRIDION 的銷售額持平，因為美國神經肌肉阻斷逆轉劑市場份額的增加被歐洲仿製藥進入的影響所抵消。我們的動物保健業務銷售額成長了 2%。牲畜銷售成長 7%，反映了價格走勢以及反芻動物產品需求的增加。由於美國獸醫就診次數減少，伴侶動物銷售下降，但定價行動部分抵消了這種影響。

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 77%, consistent with last year, as the impact from unfavorable foreign exchange was offset by product mix. Operating expenses decreased 4% to $5.8 billion. There were no significant business development expenses in the quarter, compared with $690 million of charges a year ago. Excluding these charges, operating expenses grew 9%. This growth reflects increased investments in support of our robust early- and late-phase pipeline, with research and development expenses increasing 17%. Other expense was $133 million. Our tax rate was 15%. Taken together, earnings per share was $2.13.

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 77%，與去年持平，因為不利外匯的影響被產品組合所抵消。營運費用下降 4% 至 58 億美元。本季沒有重大業務開發費用，去年同期為 6.9 億美元。扣除這些費用，營運費用增加了 9%。這一成長反映出為支持我們強大的早期和後期產品線而增加的投資，研發費用增加了 17%。其他費用為 1.33 億美元。我們的稅率是15%。合計每股收益為 2.13 美元。

Before I cover the outlook for the balance of the year, I wanted to briefly touch upon the recently announced strategic collaboration with Daiichi Sankyo. This transaction follows a similar derisked and disciplined financial structure as we have employed in prior successful collaborations, and we are very excited about the opportunity to create meaningful value for patients and shareholders.

在介紹今年剩餘時間的展望之前，我想先簡單談談最近宣布的與第一三共的策略合作。這項交易遵循與我們先前成功合作中所採用的類似的無風險且嚴格的財務結構，我們對有機會為患者和股東創造有意義的價值感到非常興奮。

Now turning to our 2023 non-GAAP guidance, which includes the strategic collaboration with Daiichi. The continuing operational strength of our business has enabled us to raise and narrow our full year revenue guidance. We now expect revenue to be between $59.7 billion and $60.2 billion, an increase of approximately $900 million at the midpoint. This range reflects strong double-digit underlying year-over-year revenue growth of 11% to 12%, excluding LAGEVRIO and an approximate 2 percentage point negative impact from foreign exchange, using mid-October rates. Our gross margin assumption is unchanged at approximately 77%.

現在轉向我們的 2023 年非 GAAP 指導，其中包括與 Daiichi 的策略合作。我們業務的持續營運實力使我們能夠提高和縮小全年收入指引。我們現在預計收入將在 597 億美元至 602 億美元之間，中間增加約 9 億美元。這一範圍反映了強勁的兩位數潛在年收入成長，即 11% 至 12%，不包括 LAGEVRIO 和外匯帶來的約 2 個百分點的負面影響（使用 10 月中旬的匯率）。我們的毛利率假設維持在 77% 左右不變。

We now estimate operating expenses to be between $39.8 billion and $40.4 billion. This range reflects $17.1 billion in acquisition and upfront collaboration, research and development expenses, including $5.5 billion for the collaboration with Daiichi as well as those associated with Prometheus, Imago, and Kelun. Our guidance does not assume additional significant potential business development transactions.

我們現在估計營運費用在 398 億美元至 404 億美元之間。這一範圍反映了 171 億美元的收購和前期合作、研發費用，其中包括與 Daiichi 以及與 Prometheus、Imago 和 Kelun 相關的合作的 55 億美元。我們的指導不假設額外的重大潛在業務發展交易。

We now assume other expense of approximately $200 million, which reflects updated foreign exchange expectations given recent dollar strengthening and higher net interest expense related to Daiichi. Our full year tax rate is expected to be between 39% and 40%, which includes an approximate 24.5 percentage point impact related to our business development activity. Our underlying tax rate is approximately 14.5% to 15.5%. We assume approximately 2.55 billion shares outstanding. Taken together, we expect EPS of $1.33 to $1.38. This range includes a negative impact from foreign exchange of approximately 6 percentage points versus 2022 using mid-October rates.

我們現在假設其他費用約為 2 億美元，這反映了鑑於近期美元走強以及第一核電廠相關淨利息費用增加而更新的外匯預期。我們的全年稅率預計在 39% 至 40% 之間，其中包括與我們的業務發展活動相關的約 24.5 個百分點的影響。我們的基本稅率約為 14.5% 至 15.5%。我們假設流通股數量約為 25.5 億股。綜合來看，我們預計每股收益為 1.33 美元至 1.38 美元。與 2022 年使用 10 月中旬匯率相比，此範圍包括約 6 個百分點的外匯負面影響。

Recall, our prior guidance range was $2.95 to $3.05. Including the onetime charge of $5.5 billion or $1.70 per share and an estimated $0.04 to advance the assets and financing costs from the collaboration with Daiichi, our prior guidance range would have been $1.21 to $1.31, with the midpoint of $1.26.

回想一下，我們之前的指導範圍是 2.95 美元至 3.05 美元。包括一次性費用 55 億美元或每股 1.70 美元，以及估計 0.04 美元用於預支與第一核公司合作的資產和融資成本，我們先前的指導範圍為 1.21 美元至 1.31 美元，中間值為 1.26 美元。

Our current guidance midpoint of $1.36 represents an increase resulting from the strength in our business of approximately $0.15, partially offset by an incremental headwind from foreign exchange of approximately $0.05.

我們目前的指導中點為 1.36 美元，這表明我們的業務實力增加了約 0.15 美元，但部分被外匯帶來的約 0.05 美元的增量阻力所抵消。

Now turning to capital allocation, where our priorities remain unchanged. We will continue to prioritize investments in our business to drive near- and long-term growth. We are proud of the significant progress our team is making to advance and augment our pipeline, including our collaboration with Daiichi. We will continue to invest in our pipeline which contains many assets with tremendous potential to address significant unmet medical needs, positioning us for strong performance well into the future. We remain committed to our dividend and plan to increase it over time.

現在轉向資本配置，我們的優先事項保持不變。我們將繼續優先考慮對業務的投資，以推動近期和長期成長。我們為我們的團隊在推動和擴大我們的產品線方面取得的重大進展感到自豪，包括我們與第一核電廠的合作。我們將繼續投資我們的管道，其中包含許多具有巨大潛力的資產，可以解決重大的未滿足的醫療需求，使我們在未來取得強勁的業績。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。

Business development continues to be a high priority. Our track record demonstrates our ability to identify compelling science and technologies that have the potential to advance standard of care, access such opportunities in a disciplined and capital-efficient manner, and importantly, to rapidly progress the opportunities for the benefit of the patients we serve and our shareholders. We maintain ample capacity, given our strong investment grade credit rating and cash flow to pursue additional science-driven, value-enhancing transactions going forward. We continue to execute a modest level of share repurchases.

業務發展仍然是重中之重。我們的業績記錄表明，我們有能力發現令人信服的科學和技術，這些科學和技術有可能提高護理標準，以嚴格的和資本效率高的方式獲得這些機會，更重要的是，我們能夠快速推進機會，造福我們所服務的病人和我們的股東。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未來更多的科學驅動、增值交易。我們繼續進行適度的股票回購。

To conclude, as we finish the year, we remain very confident in the outlook of our business in the near and long term, driven by the global demand for our innovative medicines and vaccines and our exceptional pipeline. We are in a position of financial and operational strength and our continued excellent execution will enable us to deliver value to patients, customers and shareholders well into the future. With that, I'd now like to turn the call over to Dean.

總而言之，在今年結束之際，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，我們對我們的近期和長期業務前景仍然充滿信心。我們擁有雄厚的財務和營運實力，持續出色的執行力將使我們能夠在未來為患者、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. Good morning, everyone. Today, I will start with our oncology programs, followed by vaccines, immunology and conclude with cardiometabolic disease.

謝謝你，卡洛琳。大家，早安。今天，我將從我們的腫瘤學計畫開始，然後是疫苗、免疫學，最後以心臟代謝疾病結束。

Over the last few years, our oncology strategy has focused on leveraging the remarkable properties of KEYTRUDA to establish a diverse clinical pipeline of candidates with novel mechanisms and modalities. This is broadly based on 3 strategic pillars, immuno-oncology, precision oncology and tissue targeting.

在過去的幾年裡，我們的腫瘤學策略重點是利用 KEYTRUDA 的卓越特性，建立具有新穎機制和模式的多樣化臨床候選藥物管道。這主要基於三個策略支柱：免疫腫瘤學、精準腫瘤學和組織標靶。

In immuno-oncology, we continue to evaluate KEYTRUDA in the metastatic and increasingly in earlier-stage disease settings, while also investigating multiple novel immuno-oncology combinations and co-formulations. With precision oncology, we are selectively targeting pathways to inhibit cancer cell growth. And in tissue targeting, we are developing agents, such as antibody drug conjugates designed to increase cancer cell sensitivity and killing.

在免疫腫瘤學方面，我們繼續在轉移性疾病和越來越多的早期疾病環境中評估 KEYTRUDA，同時也研究多種新型免疫腫瘤學組合和複合製劑。透過精準腫瘤學，我們選擇性地靶向抑制癌細胞生長的途徑。在組織靶向方面，我們正在開發藥物，例如旨在提高癌細胞敏感性和殺傷力的抗體藥物綴合物。

The latter is exemplified by our recently announced collaboration with Daiichi Sankyo. Daiichi Sankyo scientists have made pioneering contributions in advancing novel antibody drug conjugate technology with proven benefit to patients. By combining our companies' respective strength, we are well positioned to accelerate 3 clinical stage potentially first-in-class candidates with the goal of transforming the treatment paradigm.

後者的例子是我們最近宣布與第一三共（Daiichi Sankyo）的合作。第一三共的科學家在推進新型抗體藥物偶聯物技術方面做出了開創性貢獻，並已證明對患者有益。透過結合我們公司各自的優勢，我們有能力加速 3 個臨床階段的潛在一流候選藥物的開發，目標是改變治療模式。

These include patritumab deruxtecan, an investigation of fully humanized anti-HER3 ADC in Phase III. ifinatamab deruxtecan, an investigation of humanized anti-B7-H3 ADC in Phase II. And Raludotatug deruxtecan, an investigation or humanized anti-CDH6-targeted ADC in Phase I. We provided details during our investor event earlier this week, and are eager to begin working with the team. The Daiichi Sankyo collaboration complements our important ongoing alliance with Kelun-Biotech, whose talented scientists have developed their own innovative ADC platform.

其中包括 patritumab deruxtecan，這是一項針對完全人源化抗 HER3 ADC 的 III 期研究。 ifinatamab deruxtecan，一項人源化抗 B7-H3 ADC 的 II 期研究。 Raludotatug deruxtecan 是一項處於第一階段的研究或人源化抗 CDH6 靶向 ADC。我們在本週早些時候的投資者活動中提供了詳細信息，並渴望開始與該團隊合作。第一三共的合作補充了我們與科倫生物科技的重要持續聯盟，科倫生物科技的才華橫溢的科學家開發了自己的創新 ADC 平台。

At ESMO, new Phase II data for MK-2870 or SKB 264, a TROP2-targeting ADC in patients with previously treated metastatic hormone receptor positive HER2-negative breast cancer, showed encouraging antitumor activity with an objective response rate of 36.8%. This builds on existing data for MK-2870, both in triple-negative breast and non-small cell lung cancer. We are now poised to initiate larger studies, starting with non-small cell lung cancer and expand into additional tumor types.

在ESMO 上，MK-2870 或SKB 264（一種TROP2 標靶ADC）在先前接受過治療的轉移性荷爾蒙受體陽性HER2 陰性乳癌患者中的新II 期數據顯示出令人鼓舞的抗腫瘤活性，客觀緩解率為36.8%。這是建立在 MK-2870 在三陰性乳癌和非小細胞肺癌中的現有數據的基礎上的。我們現在準備啟動更大規模的研究，從非小細胞肺癌開始，擴展到其他腫瘤類型。

We are also advancing clinical development of MK-1200 and ADC targeting cloud in 18.2. Recognizing the proven benefit of KEYTRUDA in combination with chemotherapy in certain tumor types, we are exploring the tissue targeting concept by evaluating regimens combining ADCs and immunotherapy. At ESMO, in collaboration with Seagen and Astellas, potentially practice-changing survival data were presented from KEYNOTE-A39, EV-302, evaluating KEYTRUDA plus enfortumab vedotin as first-line treatment for patients with locally advanced or metastatic urothelial carcinoma. This regimen represents the first approval of a combination of a checkpoint inhibitor and an ADC.

我們也正在18.2中推進MK-1200和ADC靶向雲的臨床開發。認識到 KEYTRUDA 與化療聯合治療某些腫瘤類型的已被證明的益處，我們正在透過評估 ADC 和免疫療法相結合的方案來探索組織標靶概念。 ESMO 與 Seagen 和 Astellas 合作，提供了來自 KEYNOTE-A39、EV-302 的可能改變實踐的生存數據，評估 KEYTRUDA 聯合 enfortumab vedotin 作為局部晚期或轉移性尿路上皮癌患者的一線治療。該方案代表了檢查點抑制劑和 ADC 組合的首次批准。

Turning to immuno-oncology. Evidence continues to emerge for the benefit of KEYTRUDA in the treatment of earlier stage cancer. Positive survival data from KEYNOTE-671, evaluating KEYTRUDA in combination with platinum doublet chemotherapy as neoadjuvant therapy, followed by adjuvant KEYTRUDA in patients with resectable Stage 2, 3a or 3b non-small cell lung cancer compared to preoperative chemotherapy, were presented at ESMO, further reinforcing the benefit of routine lung cancer screening for certain populations to enable early intervention.

轉向免疫腫瘤學。不斷出現的證據表明 KEYTRUDA 在治療早期癌症方面具有益處。 KEYNOTE-671 的陽性存活數據在ESMO 上公佈，該數據評估了KEYTRUDA 聯合鉑類雙藥化療作為新輔助治療，然後在可切除的2、3a 或3b 期非小細胞肺癌患者中與術前化療相比進行輔助KEYTRUDA。進一步加強對某些人群進行常規肺癌篩檢的益處，以實現早期幹預。

Based on the KEYNOTE-671 results, last week, the FDA approved this indication with a differentiated label that includes overall survival. KEYTRUDA has now been approved for 6 indications to treat patients with non-small cell lung cancer. KEYNOTE-671 represents the ACE approval for KEYTRUDA in earlier stage cancer.

根據 KEYNOTE-671 結果，上週 FDA 批准了該適應症，並賦予了包括總生存期在內的差異化標籤。 KEYTRUDA 目前已被批准用於治療非小細胞肺癌患者的 6 個適應症。 KEYNOTE-671 代表 KEYTRUDA 在早期癌症治療中獲得 ACE 批准。

Positive data from additional early-stage studies in women's cancer were also presented at ESMO. For KEYNOTE-756 in patients with estrogen-receptor positive HER2-negative breast cancer. For KEYNOTE-522 and high-risk early-stage triple-negative breast cancer. And KEYNOTE A-18 for patients with high-risk locally advanced cervical cancer. Now the FDA recently granted priority review for KEYTRUDA based upon this study, with a target action date of January 20.

ESMO 也公佈了其他女性癌症早期研究的正面數據。用於雌激素受體陽性 HER2 陰性乳癌患者的 KEYNOTE-756。用於 KEYNOTE-522 和高風險早期三陰性乳癌。 KEYNOTE A-18 適用於高風險局部晚期子宮頸癌患者。現在 FDA 最近根據這項研究授予了 KEYTRUDA 優先審查資格，目標行動日期為 1 月 20 日。

We also announced KEYTRUDA significantly improved disease-free survival for the adjuvant treatment of patients with localized muscle invasive and locally advanced urothelial carcinoma based on KEYNOTE-123. And finally, in collaboration with Moderna, the Phase III trial for KEYTRUDA in combination with V940, an individualized neoantigen therapy in earlier-stage non-small cell lung cancer, has now been posted and is poised to start soon.

我們也宣布 KEYTRUDA 是基於 KEYNOTE-123 輔助治療局部肌肉浸潤性和局部晚期尿路上皮癌患者，顯著改善無疾病存活期。最後，與 Moderna 合作，KEYTRUDA 聯合 V940（一種治療早期非小細胞肺癌的個人化新抗原療法）的 III 期試驗現已發布，並將很快開始。

In Precision Oncology, our efforts continue to yield progress. WELIREG, our HIF-2 alpha inhibitor, is approved for treatment of certain cancers and patients with Von Hippel-Lindau disease, a rare cancer-prone genetic disorder. Studies evaluating WELIREG in broader populations of patients whose tumors display analogous genetic underpinnings are ongoing.

在精準腫瘤學領域，我們的努力不斷取得進展。我們的 HIF-2 α 抑制劑 WELIREG 已被批准用於治療某些癌症和馮希佩爾-林道病（一種罕見的易患癌症的遺傳性疾病）患者。在更廣泛的腫瘤顯示類似遺傳基礎的患者群體中評估 WELIREG 的研究正在進行中。

Data presented at ESMO from LITESPARK-005 evaluating WELIREG for adult patients with advanced renal cell carcinoma, following immune checkpoint and anti-angiogenic therapies, showed statistically significant and clinically meaningful improvement in progression-free survival versus the standard of care. These findings support our supplemental new drug application for WELIREG, which was granted priority review by the FDA with a target action date of January 17. Additional Phase III studies in combination with KEYTRUDA and lenvatinib in advanced and adjuvant renal cell carcinoma are proceeding.

在ESMO 上提交的LITESPARK-005 數據評估了WELIREG 對晚期腎細胞癌成年患者的免疫檢查點和抗血管生成治療後的效果，結果顯示，與標準治療相比，無進展生存期有統計學意義和臨床意義的改善。這些發現支持了我們對WELIREG 的補充新藥申請，該申請已獲得FDA 優先審查，目標行動日期為1 月17 日。與KEYTRUDA 和樂伐替尼聯合治療晚期和佐劑腎細胞癌的其他III 期研究正在進行中。

First-time safety and preliminary efficacy data for MK-1084, our oral KRAS inhibitor, both as monotherapy in patients with solid tumors and in combination with KEYTRUDA for metastatic non-small cell lung cancer whose tumors harbored KRAS G12C mutations, were presented at ESMO. Notably, the combination arm showed a compelling objective response rate of 71%. While the data are early, we are encouraged by the potential to combine MK-1084 with KEYTRUDA.

我們的口服KRAS 抑制劑MK-1084 的首次安全性和初步療效數據已在ESMO 上公佈，該藥物既可以作為實體瘤患者的單一療法，也可以與KEYTRUDA 聯合治療腫瘤攜帶KRAS G12C 突變的轉移性非小細胞肺癌。值得注意的是，合併治療組的客觀反應率為 71%，令人信服。雖然數據還為時過早，但我們對 MK-1084 與 KEYTRUDA 結合的潛力感到鼓舞。

In the hematologic space, we will begin enrolling patients in our Phase III study evaluating MK-3543 or bomedemstat, a second-line treatment for essential thrombocythemia, an area with tremendous patient need. Bomedemstat is derived from our acquisition of Imago.

在血液學領域，我們將開始招募患者參加我們的 III 期研究，評估 MK-3543 或 bomedemstat，這是一種治療原發性血小板增多症的二線治療方法，這是一個患者需求巨大的領域。 Bomedemstat 源自於我們對 Imago 的收購。

Outside of the U.S., the European Union granted approval for KEYTRUDA for adjuvant treatment of patients with non-small cell lung cancer who are at high risk of recurrence, following complete resection and platinum-based chemotherapy based on KEYNOTE-091. And for KEYTRUDA, in combination with trastuzumab and chemotherapy, as first-line treatment for patients with certain gastric or gastroesophageal junction adenocarcinoma based on KEYNOTE-811.

在美國以外，歐盟批准 KEYTRUDA 用於在完全切除和基於 KEYNOTE-091 的鉑類化療後復發風險高的非小細胞肺癌患者的輔助治療。而對於KEYTRUDA來說，合併曲妥珠單抗和化療，作為基於KEYNOTE-811的某些胃或胃食道交界腺癌患者的第一線治療。

In Japan, Lynparza, in combination with Abiraterone and Prednisone was approved for BRCA-mutated metastatic castration-resistant prostate cancer with distant metastasis based on the PROpel study.

在日本，根據 PROpel 研究，Lynparza 合併阿比特龍和潑尼松被批准用於治療 BRCA 突變、遠端轉移的轉移性去勢抵抗性前列腺癌。

Now to our broader pipeline. Building on the ongoing launch of VAXNEUVANCE, which Caroline mentioned, progress continues in our population-focused pneumococcal conjugate vaccine program. V116, our investigational pneumococcal conjugate vaccine specifically designed for adults, has demonstrated a robust immune response to all 21 serotypes in the STRIDE-3 and STRIDE-6 studies. Detailed findings from the STRIDE-3 study will be presented at the World Vaccine Congress West Coast in November. If approved, V116 would be the first pneumococcal conjugate vaccine specifically designed to address serotypes responsible for the majority of adult invasive pneumococcal disease in adults.

現在我們更廣泛的管道。 Caroline 提到，在正在推出的 VAXNEUVANCE 的基礎上，我們以人群為中心的肺炎球菌結合疫苗計劃繼續取得進展。 V116 是我們專為成人設計的研究性肺炎球菌結合疫苗，在 STRIDE-3 和 STRIDE-6 研究中已證明對所有 21 种血清型具有強大的免疫反應。 STRIDE-3 研究的詳細結果將於 11 月在西海岸舉行的世界疫苗大會上發表。如果獲得批准，V116 將成為第一種專門針對導致大多數成人侵襲性肺炎球菌疾病的血清型而設計的肺炎球菌結合疫苗。

Our company has deep expertise, given our breadth and depth of knowledge, both in immuno-oncology and vaccines. We are leveraging these capabilities in immunology where the first patient is ready to be enrolled in the Phase III trial for MK-7240 in ulcerative colitis.

鑑於我們在免疫腫瘤學和疫苗方面知識的廣度和深度，我們公司擁有深厚的專業知識。我們正在利用這些免疫學能力，第一位患者已準備好參加 MK-7240 治療潰瘍性結腸炎的 III 期試驗。

Turning to cardiometabolic disease programs. Last month at the European Respiratory Society International Congress, we presented data for Sotatercept, currently under review by the FDA for the treatment of adults with pulmonary arterial hypertension. In an exploratory post-hoc analysis of right heart catheterization and echocardiography data from patients in the Phase III STELLAR study, patients with PAH treated with Sotatercept for 24 weeks on top of background therapy showed a reduction in right heart size and improved right ventricular function and hemodynamic status.

轉向心臟代謝疾病計劃。上個月在歐洲呼吸學會國際大會上，我們展示了 Sotatercept 的數據，目前正在接受 FDA 審查，用於治療成人肺動脈高壓。在對III 期STELLAR 研究中患者的右心導管插入術和超音波心動圖數據進行的探索性事後分析中，PAH 患者在背景治療基礎上接受Sotatercept 治療24 週，結果顯示右心體積縮小，右心室功能改善，且血流動力學狀態。

In addition, we presented promising data from an analysis of the Phase III Soteria open-label extension study in PAH. The results support the potential long-term durability of the response to Sotatercept and represent the longest safety and efficacy analysis for this compound to date. Given the serious patient need in pulmonary arterial hypertension, our regulatory and clinical teams work swiftly to submit the necessary regulatory filings for Sotatercept.

此外，我們還提供了來自 PAH III 期 Soteria 開放標籤擴展研究分析的有希望的數據。結果支持 Sotatercept 反應的潛在長期持久性，並代表了迄今為止對該化合物最長的安全性和有效性分析。鑑於肺動脈高壓患者的嚴重需求，我們的監管和臨床團隊迅速工作，提交 Sotatercept 必要的監管文件。

The FDA has accepted the biologics license application under priority review, with a target action date of March 26. In addition, the submission to the Committee for Medicinal Products for human use in the European Union has been completed.

FDA已接受優先審查的生物製劑許可申請，​​目標行動日期為3月26日。此外，向歐盟人用藥品委員會提交的申請也已完成。

Also in cardiology, momentum continues in the clinical development program for MK-0616, or our PCSK9 inhibitor. We have initiated the coral reef lipid study in a broad patient population and coral reef outcomes, a randomized double-blind study evaluating the efficacy of MK-0616, with respect to major atherosclerotic cardiovascular events as well as a separate coral reef study in patients with heterozygous familial hypercholesterolemia.

同樣在心臟病學領域，MK-0616（即我們的 PCSK9 抑制劑）的臨床開發計劃繼續保持勢頭。我們已經在廣泛的患者群體和珊瑚礁結果中啟動了珊瑚礁脂質研究，這是一項評估MK-0616 在主要動脈粥樣硬化心血管事件方面的功效的隨機雙盲研究，以及針對患有以下疾病的患者的單獨珊瑚礁研究：雜合子家族性高膽固醇血症。

Over the last 3 years, we have moved with rigor and urgency to advance the best science, while carefully coordinating our efforts internally and externally. We have and continue to leverage the foundational properties of KEYTRUDA, while adding promising candidates with novel mechanisms and modalities in oncology.

在過去的三年裡，我們嚴謹而迫切地推動最好的科學發展，同時仔細協調我們內部和外部的努力。我們已經並將繼續利用 KEYTRUDA 的基本特性，同時添加具有腫瘤學新穎機制和模式的有前途的候選藥物。

At the same time, we have expanded in our focused areas of excellence to establish a diverse pipeline of promising candidates spanning multiple additional disease areas. We understand there is still work to be done, but the tangible advances we are making underscore our purpose of creating innovative medicines and vaccines that save and improve lives. And now I turn the call back to Peter.

同時，我們擴大了我們重點關注的卓越領域，建立了涵蓋多個其他疾病領域的多樣化候選藥物管道。我們知道仍有工作要做，但我們正在取得的實際進展強調了我們創造創新藥物和疫苗來拯救和改善生命的目標。現在我把電話轉回給彼得。

Thanks, Dean. Julie, we're ready to take questions. And as usual, we request that analysts limit themselves to a single question, please.

謝謝，迪恩。朱莉，我們準備好回答問題了。像往常一樣，我們要求分析師只回答一個問題。

(Operator Instructions)

（操作員說明）

Our first question comes from Chris Shibutani with Goldman Sachs.

我們的第一個問題來自高盛的 Chris Shibutani。

The comments from the capital allocation standpoint seem to indicate that you feel that you've done some critical mass, and certainly some of the deals that you've done have been very important and meaningful. You set the cardiovascular revenue goal in 2030 to $10 billion. Do you think you've done enough there? And then to provoke relatedly, Animal Health, do you still feel that, that fits within the portfolio you've been building, but is there a reshaping that you could talk?

從資本配置的角度來看，您的評論似乎表明您認為您已經完成了一些關鍵的工作，當然您所做的一些交易非常重要且有意義。您將 2030 年心血管收入目標設定為 100 億美元。你認為你已經做得足夠了嗎？然後，為了引發相關的動物健康問題，您是否仍然認為這符合您一直在建立的投資組合，但您是否可以談論重塑？

Great, Chris. This is Rob, and I'll maybe start, and Dean or Caroline can jump in if they'd like. But first and foremost, I appreciate the comments. And as we sit here today, and Dean made reference to it, we feel very good about the progress we've made over the last couple of years through the assets we brought in. You mentioned cardiometabolic, but also immunology, the progress we're making to broaden our position in oncology, and I'll get to you in a moment. But as you mentioned, the durable growth drivers we have with vaccines and Animal Health.

太棒了，克里斯。我是羅布，也許我會開始，迪恩或卡洛琳如果願意的話也可以加入。但首先，我很欣賞這些評論。當我們今天坐在這裡時，迪恩提到了這一點，我們對過去幾年通過我們引進的資產所取得的進展感到非常滿意。你提到了心臟代謝，還有免疫學，我們的進展我們正在努力擴大我們在腫瘤學領域的地位，我稍後會與您聯繫。但正如您所提到的，我們在疫苗和動物保健方面擁有持久的成長動力。

But specifically to the cardiometabolic area, I can tell you that today, as we sit here, and just to remind people what we had commented on in the past, we've said, based on both what we received through the acquisition of Acceleron plus other programs we've been developing internally, we expected that we could be in a position to have greater than $10 billion of revenue potential in the mid-2030s. And I'd remind everyone that was on a nonrisk-adjusted basis.

但具體到心臟代謝領域，我可以告訴你們，今天，當我們坐在這裡時，只是為了提醒人們我們過去的評論，我們已經說過，基於我們通過收購 Acceleron plus 獲得的信息根據我們內部開發的其他計劃，我們預計到2030 年代中期，我們的收入潛力可能會超過100 億美元。我想提醒大家，這是在非風險調整的基礎上進行的。

But I would tell you, as we sit here today, given what we've seen with the remarkable data from STELLAR, the excitement that is coming and we're seeing from key opinion leaders with the potential launch of Sotatercept hopefully early next year and approval even in Europe next year, our confidence that we will achieve that $10-plus billion is higher today than it was when we made the original comment. So we feel very good. It doesn't mean we feel like we're done, but we feel very good about the progress.

但我想告訴你，當我們今天坐在這裡時，考慮到我們從 STELLAR 看到的出色數據，即將到來的興奮，我們從關鍵意見領袖那裡看到了 Sotatercept 希望在明年初推出，即使明年在歐洲也能獲得批准，但我們今天對實現10 多億美元的信心比我們最初發表評論時更高。所以我們感覺很好。這並不意味著我們感覺已經完成了，但我們對進展感到非常滿意。

And then as you reflected on Animal Health, we continue to see the Animal Health business as an important business for us. It is a durable growth driver. As we look forward, it continues to be a business that we think will be accretive to our growth, long term. And it has strategic value to us, where we're both benefiting from the synergies that it brings to us, and that it benefits from the synergies coming from the science that we have on the Human Health side.

然後，正如您對動物保健的反思一樣，我們仍然將動物保健業務視為我們的重要業務。這是一個持久的成長動力。展望未來，我們認為這仍然是一項有利於我們長期成長的業務。它對我們具有戰略價值，我們既受益於它帶給我們的協同效應，也受益於我們在人類健康方面所擁有的科學的協同效應。

So as we sit here today, we remain committed that it is the strategic part of the company. But as I've often said, that's not a philosophical view that is unchangeable. It's something we're very objective about and we look at regularly. But I can tell you, as we've continued to look at it, our view has not changed.

因此，當我們今天坐在這裡時，我們仍然致力於將其視為公司的策略部分。但正如我常說的，這並不是一個一成不變的哲學觀點。我們對此非常客觀，並且會定期關注。但我可以告訴你，隨著我們繼續關注這個問題，我們的觀點沒有改變。

I would just add one thing, Chris, in relationship to your question but not related to revenue for finance. I would just remind that we have made incredible advances in cancer, and we're known as an oncology company, but the unmet need, the unmet patient need in cardiovascular and metabolic diseases in the U.S. and in the world is quite substantial. And I don't know that we're ever going to be done with that field in the near term. So we are still very committed to do more.

克里斯，我只想補充一件事，與你的問題有關，但與財務收入無關。我想提醒一下，我們在癌症領域取得了令人難以置信的進展，我們被稱為一家腫瘤學公司，但在美國和世界範圍內，心血管和代謝疾病方面未滿足的需求、未滿足的患者需求是相當巨大的。我不知道我們是否會在短期內完成該領域的開發。所以我們仍然非常致力於做更多的事情。

Our next question comes from Mara Goldstein with Mizuho.

我們的下一個問題來自瑞穗的瑪拉‧戈爾茨坦。

I'm curious, the discussion around KEYTRUDA and migrating components of the revenue to earlier lines of therapy. Relative to when you first made statements about where you expect it to be from a percentage, do you think you're ahead of that at this point in time or on track to where you originally thought you'd be today?

我很好奇圍繞 KEYTRUDA 以及將部分收入轉移到早期療法的討論。相對於您第一次以百分比形式表達您的預期時，您認為此時您是否領先於該百分比，或者是否正在朝著您最初認為今天的水平邁進？

Yes. The short answer, Mara is, we are ahead of our -- where we thought we would be. And just to remind everyone, we've been commenting that we expect 50% of our growth to come from movement into the earlier stages of disease in oncology as we look forward to ultimately get to a global percent with it being about 25% of our total revenues. But I can tell you, as where we sit here today, we are tracking ahead of where we expected we would be.

是的。瑪拉的簡短回答是，我們領先於我們的預期。只是為了提醒大家，我們一直在評論說，我們預計 50% 的增長將來自腫瘤學疾病早期階段的發展，因為我們期待最終達到全球百分比，約為我們的 25%總收入。但我可以告訴你，正如我們今天坐在這裡的那樣，我們正在超越我們的期望。

And obviously, not surprising when you see the phenomenal results from KEYNOTE-671, what that's going to mean in the perioperative space for people in early-stage lung cancer, building on 091, the continued strength we're seeing across adjuvant and RCC and melanoma. We're up now to 8 approvals in this space. So we're in a very good position, but maybe I'd ask Caroline if she has anything she'd like to add.

顯然，當您看到KEYNOTE-671 的驚人結果時，這對早期肺癌患者的圍手術期意味著什麼，這並不奇怪，它建立在091 的基礎上，我們在佐劑和RCC 上看到了持續的優勢，黑色素瘤。目前，我們在該領域已獲得 8 項批准。所以我們處於非常有利的位置，但也許我會問卡羅琳是否有什麼要補充的。

The only thing I'd add, Rob, is to your point, we've made tremendous progress. We think this year, we will have 20% of our KEYTRUDA business coming from the earlier stage cancer setting. And as we move forward, given the tremendous data we've had and the indications coming, we're really excited about the opportunity to further grow in lung, in potentially bladder and many other indications.

羅布，我唯一要補充的是，就你的觀點而言，我們已經取得了巨大的進步。我們認為今年我們 20% 的 KEYTRUDA 業務將來自早期癌症治療。隨著我們的前進，考慮到我們已經掌握的大量數據和即將出現的適應症，我們對有機會在肺部、潛在的膀胱和許多其他適應症中進一步發展感到非常興奮。

Yes. I just want to make a call out because we had an investor discussion this past Sunday and it really focused on the ADC and Daiichi Sankyo and Kelun. But I just want to call out that for me, KEYNOTE-671 is a watershed moment for the field. I would remind everyone that a similar watershed happened in metastatic lung cancer in 2018, KEYNOTE-189.

是的。我只是想大聲疾呼，因為上週日我們進行了一次投資者討論，討論的重點是 ADC 以及第一三共和科倫。但我只想指出，對我來說，KEYNOTE-671 是該領域的分水嶺時刻。我想提醒大家，2018年轉移性肺癌也發生了類似的分水嶺，KEYNOTE-189。

And 2018 is when KEYNOTE-671 was initiated. It's an earlier stage. And only after 5.5 years, after only 5.5 years in an earlier stage trial, you have clear evidence of EFS and OS benefit. And I really think this will catalyze a change in how we treat early-stage lung cancer, how we detect early lung cancer and how we screen.

2018 年是 KEYNOTE-671 啟動的時間。這是早期階段。僅在 5.5 年後，在早期試驗中僅 5.5 年後，您就有了 EFS 和 OS 益處的明確證據。我真的認為這將促進我們治療早期肺癌的方式、檢測早期肺癌的方式以及篩檢方式的改變。

If you think about treating early, those patients with Stage 2 and 3, you can reduce the mortality by 28%. I think it will catalyze people really looking at anyone going to surgery in Stage 2 and 3, not just in 3. People are going to have to think very carefully on why someone should get this regimen.

如果您考慮儘早治療第 2 期和第 3 期患者，則可以將死亡率降低 28%。我認為這將促使人們真正關注在第二階段和第三階段進行手術的人，而不僅僅是在第三階段。人們將不得不非常仔細地思考為什麼有人應該接受這種治療方案。

In terms of detecting early, I think it's really important. How many individuals have a chest CT or a chest X-ray with incidental findings, and there's little follow-up and day-and-age of electronic health records, it's very easy to figure out how many people have incidental nodules that never got followed up. I think that will change.

就及早發現而言，我認為這非常重要。有多少人做過胸部 CT 或胸部 X 光檢查，但有偶然發現的情況，而且電子健康記錄很少有隨訪和日齡，很容易算出有多少人偶然有結節，但從未得到跟踪向上。我認為這將會改變。

And I think in screening early, we have guidelines where the adherence is only 6% to 7%. And these guidelines were set 4, 5 years ago, where the concept was it would reduce mortality by 20%. With the data that we have, that number is no longer at 20%. It's much lower. And so I think there will be a push by the American Cancer Society, NCCN, NCI, NIH to simplify and broaden those guidelines because that is -- this is the inexorable march of I/O into earlier stage and into the most important cancer, which is lung cancer, which is the #1 cause of death for women and the #1 cause for men.

我認為在早期篩檢中，我們有指導方針，堅持率只有 6% 到 7%。這些指導方針是四、五年前製定的，其概念是可以將死亡率降低 20%。根據我們掌握的數據，這個數字不再是 20%。低得多。因此，我認為美國癌症協會、NCCN、NCI、NIH 將推動簡化和擴大這些指南，因為這是 I/O 進入早期階段和最重要癌症的不可阻擋的進程，這就是肺癌，它是女性的第一大死因和男性的第一大死因。

And our commitment to this field is not just 671 and 91. It is also, as we highlighted, our interest of moving INT, the individualized neoantigen therapy into earlier stage in lung cancer.

我們對這一領域的承諾不僅僅是 671 和 91。正如我們所強調的那樣，我們也有興趣將 INT（個人化新抗原療法）轉移到肺癌的早期階段。

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。

Great. Maybe at the risk of going back to that ADC topic, one of the key questions and sort of the back and forth have come out in the TROP2 space is just the ability to combine your TROP2 with I/O going forward. Been a lot of commentary on the myelosuppression there and to the extent that may restrict your ability to combine with I/O. Dean, I'd love to get your thoughts there and any additional commentary you can provide.

偉大的。也許冒著回到 ADC 主題的風險，TROP2 領域出現的關鍵問題和反覆討論之一就是將 TROP2 與 I/O 結合起來的能力。關於那裡的骨髓抑制有很多評論，在某種程度上可能會限制你與 I/O 結合的能力。 Dean，我很想了解您的想法以及您可以提供的任何其他評論。

Yes, specifically to any ADC that we would advance in any tissue tumor type. One thinks about monotherapy, and one thinks about a clear indication and a line of sight. But one also think about how the field develops and in combinations. And those combinations can be with PD-1s, but I would also highlight it can be with chemo, it can be RAS, it can be with novel, hormonal agents, it can be with PARP, it can be with other ADCs. And you have to think from late and earlier.

是的，特別是對於我們將在任何組織腫瘤類型中推進的任何 ADC。一個人考慮單一療法，一個人考慮明確的適應症和視線。但我們也要思考該領域如何發展以及如何組合。這些組合可以與 PD-1 結合，但我還要強調它可以與化療結合，可以與 RAS 結合，可以與新型激素藥物結合，可以與 PARP 結合，也可以與其他 ADC 結合。而且你必須從晚到早思考。

In relationship that TROP2 specifically in non-small cell lung cancer, I believe that I have said in the past that one has to think about how the field has evolved. There was a watershed moment. It was KEYNOTE-189. And pembro plus chemo in a broad patient population along that indication do really well. So those of us who want to advance what I would say in ADC, a next-gen chemo, that's how I think about it, have to think about a way to combine it with PD-1 in a way that is not just effective, but substantially effective over KEYNOTE-189.

TROP2 與非小細胞肺癌的關係，我相信我過去曾說過，人們必須思考這一領域是如何發展的。有一個分水嶺時刻。這是 KEYNOTE-189。 Pembro 加化療在廣泛的患者群體中沿著該適應症的效果非常好。因此，我們這些想要推進我所說的 ADC（下一代化療）的人，這就是我的想法，必須考慮一種將其與 PD-1 結合的方法，這種方法不僅有效，但比KEYNOTE- 189 顯著有效。

We are very interested in advancing our TROP2 ADC in relationship to that in that combination. Like all chemotherapy-based treatments, whether it's chemotherapy or whther chemotherapy on a payload with ADC, one has to think about adverse effects and combinatorial adverse effects and the ability to keep patients on the medicine.

我們非常有興趣推進我們的 TROP2 ADC 與該組合的關係。與所有基於化療的治療一樣，無論是化療還是使用 ADC 進行有效負載化療，都必須考慮不良反應和組合不良反應以及讓患者繼續用藥的能力。

The data that we have shown with our partner, our valued partner, Kelun, is that we think that there is room to be able to advance MK-2870 and PD-1 in a variety of tumors and that they are combinable, tolerable and will be effective. But those are the trials that we're starting to do in Phase III in the ex-China regulatory arena.

我們與我們的合作夥伴、我們尊貴的合作夥伴科倫公司展示的數據是，我們認為MK-2870和PD-1在多種腫瘤中還有推進的空間，並且它們是可組合的、可耐受的並且將要有效果。但這些是我們在中國以外監管領域的第三階段開始進行的試驗。

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。

So just wanted to talk about margins and some of the margin targets that you've offered, I think, historically, you called out 2024 margin target of better than 42%. Just trying to get a better sense of how we're tracking towards that target. Particularly in the context of the substantial reduction in your royalty burden, both for KEYTRUDA and GARDASIL. And if you wouldn't mind, would you perhaps disclose what that cumulative royalty burden was in the third quarter of this year, just so that we can provide some context for the upside case or at least what we should be anticipating there?

因此，我只想談談利潤率和您提出的一些利潤率目標，我認為，從歷史上看，您提出的 2024 年利潤率目標高於 42%。只是想更了解我們如何實現該目標。特別是在 KEYTRUDA 和 GARDASIL 的特許權使用費負擔大幅減少的背景下。如果您不介意的話，您是否可以透露今年第三季度的累計特許權使用費負擔是多少，以便我們可以為上行情況提供一些背景信息，或者至少我們應該對此進行預期？

Seamus, thank you for the question. We've seen really strong margin expansion in our company over the last several years. And as we look forward, we expect continued margin expansion. And that margin expansion really comes from the product mix on the revenue line. It also comes from the roll-off of royalties, as you've just noted, knowing that we have the royalty on our global KEYTRUDA sales going from 6.5% to 2.5% at the start of next year, and our royalty on GARDASIL going from 7% to 0% on our global sales, again at the start of next year, will drive significant gross margin improvement.

西莫，謝謝你的提問。在過去的幾年裡，我們公司的利潤率成長非常強勁。展望未來，我們預期利潤率將持續擴大。利潤率的擴張其實來自於收入線上的產品組合。正如您剛才所指出的，它也來自特許權使用費的下降，我們知道明年初我們全球 KEYTRUDA 銷售的特許權使用費將從 6.5% 降至 2.5%，而我們對 GARDASIL 的特許權使用費將從明年年初，我們的全球銷售額將再次從7% 降至0%，這將推動毛利率顯著提高。

At the same time, we will be investing in our business. We'll be disciplined in that investment, but we're investing in the portfolio of products that we have in the market and that we will be launching as well as investing in our robust and growing pipeline.

同時，我們將投資於我們的業務。我們將在投資中遵守紀律，但我們投資的是我們在市場上擁有的產品組合，我們將推出這些產品組合，以及投資於我們強大且不斷成長的產品線。

And that obviously includes the Daiichi's collaboration, where we've noted we expect about a $0.25 impact as a result of investing predominantly in the research and development of the wide range of programs that Dean has partially outlined as well as this financing cost. We also have made significant progress across our pipeline with many other collaborations, acquisitions and the progress we're making with our own internal assets.

這顯然包括 Daiichi 的合作，我們注意到，由於主要投資於 Dean 部分概述的廣泛項目的研發以及融資成本，我們預計將產生約 0.25 美元的影響。我們也透過許多其他合作、收購以及我們利用自己的內部資產取得的進展，在整個管道上取得了重大進展。

So altogether, we still do point to an operating margin of greater than 43% in the year 2025. However, we will not forgo necessary investments in our business to progress our pipeline to ensure that we advance health care and drive growth, which really is our priority.

因此，總的來說，我們仍然預計2025 年的營業利潤率將超過43%。但是，我們不會放棄對業務進行必要的投資，以推進我們的產品線，以確保我們推進醫療保健並推動成長，這確實是我們的首要任務。

Our next question comes from Terence Flynn with Morgan Stanley.

我們的下一個問題來自摩根士丹利的特倫斯·弗林。

I guess another one for Dean on the TROP2 landscape. I know you guys talked over the weekend about your first Phase III trial in lung cancer here. Maybe just any more context on the decision to pursue the EGFR mutant population, given what you're seeing from the landscape out there, including some of the Astra data. And then what that means for the frontline setting as you try to craft a trial in that broader population.

我猜 Dean 在 TROP2 領域還有另一件事。我知道你們週末在這裡談論了你們的第一個肺癌 III 期試驗。考慮到你從那裡看到的情況，包括一些 Astra 數據，也許只是關於追求 EGFR 突變群體的決定的更多背景。當你試圖在更廣泛的人群中進行試驗時，這對前線環境意味著什麼。

Yes. So I just want to make sure that whether we're talking about our wonderful partnership with Kelun or with Daiichi Sankyo, we sort of lay out certain indications that becomes public, but I want to be very clear that those are not the only indications that we would be interested. So that's number one.

是的。因此，我只是想確保，無論我們是在談論與科倫還是與第一三共的良好合作關係，我們都會列出一些公開的跡象，但我想非常明確的是，這些並不是唯一的跡像我們會感興趣的。所以這是第一。

Number two, in relationship to MK-2870 and advancing it more broadly. And it relates to the other question. There is -- we still have small numbers. But what's really interesting for us is 2870, there are differences in the construct in terms of its payload, in terms of the linker, in terms of the [DOA] for that. And one of the things that's interesting to us is, at least to date, we do not see serious ILD. And that allows us to think broadly and thoughtfully about its combinability in relationship to broader indications. So we're very interested in advancing.

第二，與 MK-2870 相關並更廣泛地推進它。這與另一個問題有關。我們的人數仍然很少。但對我們來說真正有趣的是 2870，在其有效負載、連結器、[DOA] 方面，其結構存在差異。我們感興趣的事情之一是，至少到目前為止，我們還沒有看到嚴重的間質性肺病。這使我們能夠廣泛而深思熟慮地思考其與更廣泛適應症的組合性。所以我們對進步非常感興趣。

In terms of 2870 and the specific first trial that's been revealed, it's -- I'll just tell you, it was driven because of the data that we have, and the data that we have we think is quite good and should be advanced. We are going to advance other ones, but the advancement in the EGFR mutant population is based on data that our partners, Kelun and us have generated, and we're very confident in advancing in that specific indication.

就 2870 和已披露的具體第一次試驗而言，我只是告訴你，它是由我們擁有的數據驅動的，我們認為我們擁有的數據非常好，應該先進。我們也將推動其他方面的工作，但EGFR突變族群的進展是基於我們和科倫合作夥伴產生的數據，我們對在該特定適應症上的進展非常有信心。

Our next question comes from Andrew Baum with Citi.

我們的下一個問題來自花旗銀行的安德魯鮑姆。

Question in relation to TIGIT and vibostolimab and your KEYVIBE-003 trial. I'm assuming that you are using a similar type clinical design and template for the stats from KEYNOTE-042, where you have a hierarchy. Given this is a PD-L1-enriched trial with the hierarchy in place, we were expecting an interim potentially at the very end of next year, beginning of the following year. Any comments on either design or timing of interims?

有關 TIGIT 和 vibostolimab 以及您的 KEYVIBE-003 試驗的問題。我假設您正在使用類似類型的臨床設計和 KEYNOTE-042 中的統計資料模板，其中您有一個層次結構。鑑於這是一項富含 PD-L1 的試驗，且層級結構已就位，我們預計可能會在明年底、明年初進行臨時試驗。對臨時的設計或時間安排有何評論？

I would just say that in general principle, your observations of how we develop drugs, especially in the I/O, has been something that we're known for and the structure was laid out by by great leaders from Merck who laid the basis for that. In relationship to timing of interim analysis, we have generally not commented on interim analysis. And we let those interim analysis do what they need to do, which has come. And if they're significant, we make that publicly known. If there's significance in relationship to public disclosure, that's when we do that. But we generally do not lay out the timing of our interim analysis prior to them happening.

我只想說，一般原則上，您對我們如何開發藥物的觀察，特別是在 I/O 中，我們已經眾所周知，並且該結構是由默克公司的偉大領導人制定的，他們為那。關於中期分析的時間安排，我們一般不會對中期分析發表評論。我們讓這些臨時分析做他們需要做的事情，這些事情已經發生了。如果它們很重要，我們就會公開。如果公開揭露具有重要意義，我們就會這麼做。但我們通常不會在這些事件發生之前安排中期分析的時間。

Our next question comes from Louise Chen with Cantor.

我們的下一個問題來自 Louise Chen 和 Cantor。

I wanted to ask you about Sotatercept, how you're preparing for that launch. What's your go-to-market strategy? And how quick do you expect uptake to be?

我想向您詢問有關 Sotatercept 的情況，您是如何為該產品的上市做準備的。您的上市策略是什麼？您預計吸收速度有多快？

Yes, Louise, this is Rob. I'll maybe jump in, and Caroline can add if I miss anything. I would tell you that we feel well prepared. So obviously, we've been working to ensure we have supply to be able to supply the market upon launch. But as we sit here today, given what is happening in the marketplace -- so you are seeing warehousing of patients in anticipation of the launch of Sotatercept in the United States. And from feedback from key opinion leaders and what we're hearing from the market, the demand for this will be quite high. So our expectation is you will see a strong launch with this drug.

是的，路易絲，這是羅布。我也許會插話，如果我錯過了什麼，卡洛琳可以補充。我想告訴你，我們感覺已經做好了充分的準備。顯然，我們一直在努力確保我們有供應，以便能夠在推出後供應市場。但當我們今天坐在這裡時，考慮到市場上正在發生的事情——所以你會看到患者在等待 Sotatercept 在美國上市。從主要意見領袖的回饋以及我們從市場聽到的情況來看，對此的需求將會相當高。因此，我們期望您會看到該藥物的強勁上市。

And I can tell you, we've invested and built an organization. We actually have a very focused group now in our U.S. -- within our U.S. business, whose sole job is to manage this launch. And so I think we're both prepared from a commercial perspective and from a manufacturing perspective, with the expectation, as I said, that this should go with a very strong quick uptake.

我可以告訴你，我們已經投資並建立了一個組織。事實上，我們現在在美國有一個非常專注的團隊——在我們的美國業務範圍內，他們的唯一工作就是管理這次發布。因此，我認為我們從商業角度和製造角度都做好了準備，正如我所說，我們期望這應該會得到非常強烈的快速接受。

And the other thing I would highlight is, given the strength of the data, we do expect to see approval in Europe next year, which we originally thought would require a further study. So not only are we preparing in the United States, but we're also preparing in Europe as well, and we feel good about both. But Caroline, anything you would want to add?

我要強調的另一件事是，鑑於數據的強度，我們確實預計明年在歐洲獲得批准，我們最初認為這需要進一步研究。所以我們不僅在美國做準備，也在歐洲做準備，我們對這兩方面都感覺很好。但是卡羅琳，你還有什麼要補充的嗎？

No, I think you captured it, Rob. Dean, anything you'd want to?

不，我想你抓住了它，羅布。迪恩，你想要什麼嗎？

Yes. I just want to emphasize Sotatercept. This is the first drug out there that really is targeting the fundamental genetic basis of the disease. It's going to be the first Activin inhibitor. But most important is, Activin is what the genetics tells you is the imbalance that occurs in pulmonary artery hypertension.

是的。我只是想強調Sotatercept。這是第一種真正針對該疾病的基本遺傳基礎的藥物。這將是第一個激活素抑制劑。但最重要的是，遺傳學告訴您，激活素是肺動脈高壓中發生的不平衡。

So this is really important. And I said watershed previously. I do think this is going to be a watershed moment for PAH. Rob already talked about the U.S. and EU. And the reason why that happened is because of STELLAR data was quite impressive. And that's what drove the ability to do EU.

所以這非常重要。我之前說過分水嶺。我確實認為這對 PAH 來說將是一個分水嶺。羅布已經談到了美國和歐盟。之所以會發生這種情況，是因為 STELLAR 的數據非常令人印象深刻。這就是推動歐盟能力的原因。

What I would remind everyone is that we have other trials coming through. We have ZENITH, HYPERION and CADENCE. ZENITH, for example, is one that's going to look at mortality and those sort of endpoints as the primary endpoints. Should that read out in the next year or something like that relatively soon to the launch, I think whatever estimates that Caroline and Rob have talked about Sotatercept, that will only help the uptake of Sotatercept. And as Rob has mentioned, this is a field that many of the physicians -- this was a place of where I did research back in the academic days. The phone calls I'm getting is that people are warehousing patients in anticipation of that March launch.

我要提醒大家的是，我們還有其他考驗正在經歷。我們有 ZENITH、HYPERION 和 CADENCE。例如，ZENITH 會將死亡率和此類終點作為主要終點。如果該消息在明年或在發布前不久發布，我認為無論 Caroline 和 Rob 談論 Sotatercept 的估計如何，都只會有助於 Sotatercept 的採用。正如羅布所提到的，這是許多醫生關注的領域——這是我在學術時代進行研究的地方。我接到的電話是，人們正在儲存患者，等待三月的推出。

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。

I just had a question on GARDASIL. We've seen obviously some very impressive growth over the past few years. But looking ahead, I'm just interested in how much more opportunity for -- you see for this franchise to ramp from here. So maybe just elaborate a little bit more on what are the kind of unmet needs at this point? Where is the biggest opportunity to continue to kind of roll out the product? And just ultimately, how much larger can this franchise become over time?

我剛剛有一個關於 GARDASIL 的問題。在過去幾年中，我們顯然看到了一些非常令人印象深刻的成長。但展望未來，我只是感興趣的是，你會看到這支球隊從現在開始會有多少更多的機會。那麼，也許只是詳細說明一下目前有哪些未滿足的需求呢？繼續推出該產品的最大機會在哪裡？最終，隨著時間的推移，這個特許經營權能變得多大？

Yes. Chris, no, I appreciate the question. So one, I would say we feel very proud of GARDASIL has -- strength of this business. And the fact that people increasingly recognize that we can fundamentally do what's the most important, which is prevent cancer, prevent cervical cancer, increasingly prevent certain head and neck cancers if we can get people fully vaccinated. So the fact that you are starting to see that progress is important.

是的。克里斯，不，我很欣賞這個問題。因此，我想說，我們對 GARDASIL 擁有的這項業務的實力感到非常自豪。事實上，人們越來越意識到，如果我們能讓人們充分接種疫苗，我們可以從根本上做最重要的事情，即預防癌症、預防子宮頸癌、越來越多地預防某些頭頸癌。因此，您開始看到進展這一事實很重要。

But as we look at the business going forward, I would start by saying we remain very confident that this is a business that's going to continue to grow and that we will achieve the expectation we've communicated of over $11 billion in revenue by 2030. So nothing has changed in how we see the business. As you know, we've made significant investments in manufacturing capacity. And from that perspective, now we're well positioned. We've brought on our 2 sites, and they're ramping now. And so we're doing quite well from that perspective.

但當我們展望未來業務時，我首先要說的是，我們仍然非常有信心，這是一項將繼續成長的業務，並且我們將實現我們所傳達的到 2030 年收入超過 110 億美元的預期。因此，我們對業務的看法沒有任何改變。如您所知，我們在製造能力方面進行了大量投資。從這個角度來看，我們現在處於有利位置。我們已經啟用了 2 個站點，並且它們現在正在擴展。所以從這個角度來看我們做得很好。

And then as far as the opportunities that exist to potentially continue to drive even beyond what we just discussed, really, I would put in 3 buckets. And our ability to achieve that objective and then potentially exceed that objective really come down to these 3 variables.

然後，就存在的可能繼續推動甚至超出我們剛才討論的範圍的機會而言，實際上，我將分為三類。我們實現該目標並可能超越該目標的能力實際上取決於這三個變數。

And first and foremost, while we've had great penetration in the developed world, a huge opportunity still exists in the low and middle income markets. And I can tell you, we have a focus and an intention to drive this business into the low and middle income markets. Obviously, that's going to require us to continue to drive down our manufacturing costs, which we have plans to do. And I have confidence that we will do. And to think about lower price points, but that said, that will be a meaningful incremental revenue as we achieve that over time.

首先也是最重要的是，雖然我們在已開發國家已經有了很大的滲透率，但中低收入市場仍然存在著巨大的機會。我可以告訴你，我們的重點和意圖是將這項業務推向低收入和中等收入市場。顯然，這將要求我們繼續降低製造成本，我們已經計劃這樣做。我有信心我們會做到。考慮到更低的價格點，但話雖如此，隨著時間的推移，這將是一個有意義的增量收入。

And then as you look at the established markets, there still is a large population to address. Obviously, to date, we've been driving largely through public vaccination programs outside the United States, in the United States through the nationalization program, primarily aimed at young women -- young girls. Increasingly, the opportunity to go to broader age cohorts as we think about going now to people age 45, that ability to move into the mid-adult segment is a real opportunity in the United States.

然後，當你觀察現有市場時，仍然有大量人口需要解決。顯然，迄今為止，我們主要透過美國境外的公共疫苗接種計劃，在美國透過國有化計劃，主要針對年輕女性——年輕女孩。越來越多的機會進入更廣泛的年齡群體，因為我們現在考慮進入 45 歲的人群，進入中成人階段的能力在美國是一個真正的機會。

It continues to be a driver of growth. It's increasingly going to be a growth driver in Europe, and it is currently an important part of why we're driving growth with the recent expansion we got in China, and there are more markets to come. So as we look at that, that's going to be another lever of growth.

它仍然是成長的驅動力。它越來越成為歐洲的成長動力，目前也是我們透過最近在中國的擴張推動成長的重要組成部分，而且還會有更多市場。因此，當我們看到這一點時，這將成為另一個成長槓桿。

Obviously, the difference here is this requires consumer activation. That takes commercial investment and a lot of heavy lifting. We've demonstrated we can do it like we've started to do in China and as we're starting to do in the United States. But it is going to take a lot of work and investment, and we're committed to doing that. So that's another variable that we look at.

顯然，這裡的區別在於這需要消費者激活。這需要商業投資和大量繁重的工作。我們已經證明我們可以做到這一點，就像我們在中國和美國開始做的那樣。但這需要大量的工作和投資，我們致力於這樣做。這是我們要考慮的另一個變數。

And then lastly, this is still largely seen as a female vaccine. We only -- I think it's only 70 markets have gender-neutral approvals. And even in the markets that do have it, particularly as you look at markets like Europe, there still is a real opportunity to increasingly bring people to understand that this is not just a female cancer vaccine, it is a gender-neutral cancer vaccine. And with the growing incidence of head and neck cancers, which is primarily a male-dominated cancer, we do see real opportunity to continue to push and drive, both getting more markets to gender-neutral and in the markets where we have those approvals drive vaccination rates up. And probably one of the bigger near-term opportunities is to get gender-neutral approved in China, which is an opportunity.

最後，這在很大程度上仍然被視為女性疫苗。我認為只有 70 個市場擁有不分性別的批准。即使在確實擁有這種疫苗的市場，特別是當你看看歐洲等市場時，仍然有一個真正的機會讓人們越來越多地了解這不僅僅是一種女性癌症疫苗，它還是一種不分性別的癌症疫苗。隨著頭頸癌（主要是男性主導的癌症）發病率的不斷上升，我們確實看到了繼續推動和推動的真正機會，既讓更多市場實現性別中立，又在我們擁有這些批准推動的市場中疫苗接種率上升。近期更大的機會之一可能是在中國獲得性別中立的批准，這是一個機會。

So across all of those, there's opportunities and potential. It's a heavy lift. I don't want to indicate that it's going to be easy. And we're going to invest behind it. But that really will determine ultimately, our success across those variables will determine the success we see long-term with this franchise. But maybe Dean or Caroline, anything you would add?

因此，在所有這些方面，都存在著機會和潛力。這是一個沉重的負擔。我不想表明這會很容易。我們將對其進行投資。但這確實將最終決定，我們在這些變數上的成功將決定我們在這個特許經營權上看到的長期成功。但也許是迪恩或卡洛琳，你還有什麼要補充的嗎？

Yes. I would just emphasize 2 points, one, directly related to what you said. This is a highly effective vaccine to prevent women's cancer, cervical cancer. And that is something that everyone recognizes, but the gender-neutral part is really important. And at MRL, we're advancing studies and filings in relationship to make sure that as many places that can adopt gender-neutral can be in that position to do gender-neutral.

是的。我只想強調兩點，第一，與你所說的直接相關。這是一種預防女性癌症、子宮頸癌的高效疫苗。這是每個人都認識到的，但性別中立的部分確實很重要。在 MRL，我們正在推進關係方面的研究和備案，以確保盡可能多的可以採用性別中立的地方能夠做到性別中立。

I also want to just make one comment about cervical cancer itself. We talk about CAR T-cell in relationship to cervical cancer, but I would also emphasize that at ESMO, we had KEYNOTE A-18. I would remind people that cervical cancer is still the fourth leading cause of women cancer, and this was another trial that showed the effect of KEYTRUDA in earlier stage in combination with chemo radiation.

我還想就子宮頸癌本身發表一點評論。我們談論 CAR T 細胞與子宮頸癌的關係，但我還要強調，在 ESMO，我們有 KEYNOTE A-18。我想提醒人們，子宮頸癌仍然是女性癌症的第四大原因，這是另一個顯示早期 KEYTRUDA 合併放化療效果的試驗。

So that, I think, is a PDUFA date that's coming up, and that hopefully might be the ninth early stage. And I believe that PDUFA date is among like 4 that are coming up in the next 6 months in relationship to cancer. So CAR T-cell gender-neutral, but also cervical cancer being a critical driver and driving into earlier stage, those are all things that play around what we're trying to do at Merck.

因此，我認為 PDUFA 日期即將到來，希望可能是第九個早期階段。我相信 PDUFA 日期是未來 6 個月內即將出現的 4 個與癌症相關的日期之一。因此，CAR T 細胞不分性別，而且子宮頸癌也是一個關鍵的驅動因素並推動其進入早期階段，這些都是我們默克正在努力做的事情。

Thanks for the question, Chris. We have time to take some additional questions and go past the hour. Julie, next question, please.

謝謝你的提問，克里斯。我們有時間回答一些其他問題並度過一個小時。朱莉，請下一個問題。

Our next question comes from Geoff Meacham with Bank of America.

我們的下一個問題來自美國銀行的傑夫·米查姆。

A question for Dean or even Rob on ADCs. So you guys have obviously done a number of deals, have partnered assets. And clearly, you think this approach is strategically important for Merck. So the question is how much of an investment is Merck making in building out a broader ADC platform, in-house? I'm just thinking beyond the partner programs and especially, Dean, as you called out, the I/O paradigm is shifting earlier.

關於 ADC 的問題，請教 Dean 甚至 Rob。所以你們顯然已經完成了很多交易，擁有合作資產。顯然，您認為這種方法對默克來說具有戰略意義。因此，問題是默克在內部建立更廣泛的 ADC 平台方面投入了多少資金？我只是在思考合作夥伴計劃之外的問題，尤其是 Dean，正如您所說，I/O 範式正在更早地轉變。

Yes. Thanks for that. I'll grab that one. So we've been very lucky to partner with Kelun and Daiichi Sankyo. And that advances our clinical programs at scale. We also clearly have collaborations with other ADC companies in relationship to KEYTRUDA. So we have a wall of data of understanding what we are hoping that the field might navigate towards.

是的。感謝那。我會抓住那個。所以我們非常幸運能夠與科倫和第一三共合作。這大規模地推進了我們的臨床計畫。我們顯然也與其他 ADC 公司就 KEYTRUDA 進行了合作。因此，我們有一堵數據牆來了解我們希望該領域能夠走向何方。

And like everyone has said, there will be different antibodies, different antibody structures to be able to change how one thinks about the tissue targeting component. There will be changes in terms of the linkers. And for right now, there are probably 2 major payloads that people use, microtubule-based chemotherapy as well as Topo 1-based chemotherapy. I would just emphasize that there are only -- there are not just 2 classes of chemotherapy out there for the last 30 years, and each one has a reason why they're there.

正如每個人所說，將會有不同的抗體、不同的抗體結構能夠改變人們對組織標靶成分的看法。連結器方面將會改變。目前，人們使用的主要有效載荷可能有兩種：基於微管的化療和基於 Topo 1 的化療。我想強調的是，在過去的 30 年裡，不僅有兩種化療方案，而且每種化療方案都有其存在的理由。

So we have invested in an ADC platform that is separate, but we'll build off what is learned from our clinical programs both in the ones that we're doing with Daiichi Sankyo and Kelun as well as those that we're doing where we're collaborating with others in relationship with KEYTRUDA. So we have built and we continue to build that expertise within the company, and we hope to see those internal programs during its clinical head in the next couple of years.

因此，我們投資了一個獨立的 ADC 平台，但我們將藉鏡從我們的臨床項目中學到的知識，無論是我們與第一三共和 Kelun 合作的臨床項目，還是我們在自己的地方所做的項目。正在與其他人就KEYTRUDA 進行合作。因此，我們已經並將繼續在公司內部建立這種專業知識，我們希望在未來幾年的臨床主管期間看到這些內部計劃。

Our next question comes from Steve Scala with TD Cowen.

我們的下一個問題來自 Steve Scala 和 TD Cowen。

What is VAXNEUVANCE's share in pediatrics now? And why hasn't it seen an inflection in the U.S. sales in line with Merck's prior comments that it held 30% share of the pediatric market with plans to grow from there? I mean 30% share of a $6 billion market is a big number, and it's well ahead of where current sales are landing. So any color would be appreciated.

VAXNEUVANCE現在在兒科的份額是多少？為什麼它在美國的銷售額沒有出現像默克公司之前所說的那樣的變化，即它佔據了兒科市場 30% 的份額，併計劃在此基礎上繼續增長？我的意思是，在 60 億美元的市場中佔 30% 的份額是一個很大的數字，而且遠遠領先於當前的銷售額。所以任何顏色都會受到讚賞。

Yes. Steve, I'll maybe jump on that and then others can jump in. But so your answer is we are in that low 30% share, both in the public and private market. So that is what you're seeing in the quarter. I think the U.S. roughly was about approaching, I think, $185 million to $200 million of total business for the products. So we're actually seeing growth pretty much consistent with what we expect, and the share we got is pretty much what we expected. So we'll have to think through how to -- the disconnect in what you're seeing, but I can tell you, in fact, we are doing exactly what we expected we would do.

是的。史蒂夫，我可能會加入進來，然後其他人也可以加入。但你的答案是，無論是在公共市場還是私人市場，我們都處於 30% 的低份額。這就是您在本季度看到的情況。我認為美國的產品總業務大約接近 1.85 億至 2 億美元。因此，我們實際上看到的成長與我們的預期基本一致，而且我們獲得的份額也與我們的預期基本一致。所以我們必須考慮如何——你所看到的脫節，但我可以告訴你，事實上，我們正​​在做我們期望做的事情。

This is Caroline. The only thing I'd add to that would be the performance we're also seeing outside of the U.S. So while we're early in our launch outside the U.S., we have gained 50% of the tenders in which we have participated, and we're shifting shares north of that 1/3. So we're very confident in our ability to continue to drive VAXNEUVANCE and very much looking forward to augmenting our offering with V116 later next year.

這是卡羅琳。我唯一要補充的是我們在美國以外地區也看到的表現。因此，雖然我們在美國以外地區的推出還處於早期階段，但我們已經贏得了所參與投標的 50%，並且我們正在將份額轉移到那1/3 以北。因此，我們對繼續推動 VAXNEUVANCE 的能力非常有信心，並且非常期待明年晚些時候透過 V116 來增強我們的產品。

Yes, I would just add...

是的，我只想補充一下...

Steve, let me just clarify one thing because I think it's important. I was just reflecting on your question. Just to clarify my comment, it's 30% is the exit share, not overall of the year. So that's an exit share as we're seeing the business grow today.

史蒂夫，讓我澄清一件事，因為我認為這很重要。我只是在反思你的問題。只是為了澄清我的評論，其中 30% 是退出份額，而不是全年的整體份額。這是退出份額，因為我們今天看到業務成長。

Yes. I wanted to just make a comment about VAXNEUVANCE in the setting of what Caroline said about V116. It's essentially with VAXNEUVANCE and V116, what we're trying to do is to drive precision medicine mindset to vaccine, giving the right vaccine with the right set of serotypes to the right age group at the right time.

是的。我想結合 Caroline 對 V116 的評價來評論 VAXNEUVANCE。本質上是透過 VAXNEUVANCE 和 V116，我們正在努力做的就是將精準醫學思維推向疫苗，在正確的時間向正確的年齡組提供具有正確血清型的正確疫苗。

And we believe that, that strategy is important for VAXNEUVANCE and to think about VAXNEUVANCE, not just on its own, but in relationship to V116. And we have work cut out to us in relationship to a potential approval from the FDA as well as we'll have to speak to the ACIP as we advance this concept of a precision medicine mindset to pneumococcal vaccination.

我們相信，這項策略對 VAXNEUVANCE 來說非常重要，並且不僅要考慮 VAXNEUVANCE 本身，還要考慮與 V116 的關係。我們還需要與 FDA 的潛在批准相關的工作，並且在我們將精準醫療理念推廣到肺炎球菌疫苗接種時，我們也必須與 ACIP 進行溝通。

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 want to touch on MK-0616. So clearly prioritizing this given the advancement into multiple Phase III trials. Maybe talk to me about the importance of an oral PCSK9 given the dynamics we've seen in the injectable market with both the antibodies and other long-acting assets?

我想談談 MK-0616。鑑於多項 III 期試驗的進展，因此明確優先考慮這一點。鑑於我們在抗體和其他長效資產的注射市場上看到的動態，也許可以和我談談口服 PCSK9 的重要性嗎？

Okay. I will take that one. And I will give my homage to Helen Hobbs and Jonathan Cohen at the UT Southwestern Dallas Heart Study. That was really important data in relationship to showing PCSK9. And if you look at that patient population, that patient population is desperately in need of an oral potent LDL-lowering cholesterol medicine, and that's what we're trying to provide. We're trying to democratize that pathway such that people, whether they're rural, in the intercity or globally, can get this.

好的。我會接受那個。我還要向 UT 西南達拉斯心臟研究中心的海倫·霍布斯和喬納森·科恩致敬。這是與顯示 PCSK9 相關的非常重要的數據。如果你觀察一下這些患者群體，你會發現這些患者群體迫切需要口服有效的降低低密度脂蛋白膽固醇的藥物，而這正是我們正在努力提供的。我們正在努力使這條道路民主化，以便人們，無論是農村的、城際的還是全球的人，都可以得到這一點。

And so I would just emphasize the other point, which is cardiovascular disease, atherosclerotic disease is still the #1 killer in the United States and the developed countries, and lowering LDL is known to be important. We used to talk about statin-resistant or refractory, but my experience is that the level of LDL that you're going to have to drive to that increasingly, the guidelines are taking this to is, forget about whether you're refractory or resistant to statins. It will be very hard with one agent to get your LDL below 70 or below 55 in some patient populations. That patient population you want to treat, you want to have that treatment readily available with no coaching and no requirement to go into a hospital system to get it. That's what we're trying to do. And hopefully, our data will support such a move.

所以我只想強調另一點，那就是心血管疾病，動脈粥狀硬化疾病仍然是美國和已開發國家的第一殺手，眾所周知，降低低密度脂蛋白很重要。我們曾經討論過他汀類藥物抗藥性或難治性，但我的經驗是，你必須不斷提高 LDL 水平，指南的目的是，忘記你是難治性還是抗藥性他汀類藥物。在某些患者群體中，僅使用一種藥物很難將 LDL 降至 70 或 55 以下。您想要治療的患者群體，您希望能夠隨時獲得治療，無需指導，也無需進入醫院系統即可獲得治療。這就是我們正在努力做的事情。希望我們的數據能夠支持這項措施。

Thanks, Evan. Maybe final question, please, Julie.

謝謝，埃文。也許是最後一個問題，朱莉。

Our next question comes from Mohit Bansal with Wells Fargo.

我們的下一個問題來自富國銀行的 Mohit Bansal。

I just want to touch upon among EGFR mutant patients. How are you thinking about a TROP2-ADC versus HER3-ADC? Because if you look at your data or even AZ's data, it seems like TROP2 seems to be working quite well among those AGA mutations. So how are you thinking about these 2 ADCs in that same indication?

我只想談談 EGFR 突變患者。您如何看待 TROP2-ADC 與 HER3-ADC？因為如果你查看你的數據甚至 AZ 的數據，你會發現 TROP2 在這些 AGA 突變中似乎表現得很好。那麼，對於同一適應症，您如何看待這 2 個 ADC？

I think that's a great question. I would just answer that I think the TROP2-ADC data is important to look at, but I would also emphasize that the HER3-ADC program is reasonably advanced in that patient population. And so we will -- we're interested in advancing both and getting the best medicines to the patients as quickly as we can.

我認為這是一個很好的問題。我只想回答說，我認為 TROP2-ADC 數據很重要，但我還要強調，HER3-ADC 計劃在該患者群體中相當先進。因此，我們有興趣推動這兩個方面的發展，並儘快為患者提供最好的藥物。

I do think more as a general statement that the role of biomarkers for some of these ADCs outside of EGFR will be important in relationship to tissue targeting, also in relationship more broadly for ADCs and other combinations. And so we'll have to see how that field is moving.

我確實認為更多的是作為一般性陳述，EGFR 以外的一些 ADC 的生物標記對於組織靶向的關係非常重要，對於 ADC 和其他組合也具有更廣泛的關係。所以我們必須看看這個領域是如何發展的。

But essentially, the way I think about ADCs is trying to bring chemotherapy in the precision medicine approach. And with that, we're going to have to find the right patient population with the right biomarkers to give them the maximum benefit.

但本質上，我對 ​​ADC 的看法是試圖將化療引入精準醫療方法中。因此，我們必須找到具有正確生物標記的正確患者群體，以使他們獲得最大的益處。

Thank you, Mohit, and thank you all for your time and attention today. Please follow up with Investor Relations if you have any additional questions. And we look forward to being in touch soon. Thank you all very much.

謝謝莫希特，也謝謝大家今天的時間和關注。如果您有任何其他問題，請聯絡投資者關係部。我們期待盡快與您聯繫。非常感謝大家。